[{"accession_id":"DUMMY_STUDY","title":"q","description":null,"abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00000000001","title":"WTCCC case-control study for Bipolar Disorder","description":"WTCCC genome-wide case-control association study for Bipolar disorder (BD) using the 1958 British Birth Cohort and the UK National Blood Service collections as controls.      ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000002","title":"WTCCC case-control study for Bipolar Disorder - Combined Controls","description":"WTCCC genome-wide case-control association study for Bipolar Disorder (BD) using six disease collections together with the 1958 British Birth Cohort and the UK National Blood Service collections as controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000003","title":"WTCCC case-control study for Coronary Artery Disease","description":"WTCCC genome-wide case-control association study for Bipolar disorder (CAD) using the 1958 British Birth Cohort and the UK National Blood Service collections as controls.      ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000004","title":"WTCCC case-control study for Coronary Artery Disease - Combined Controls","description":"WTCCC genome-wide case-control association study for Coronary Artery Disease (CAD) using six disease collections together with the 1958 British Birth Cohort and the UK National Blood Service collections as controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000005","title":"WTCCC case-control study for Coronary Artery Disease, Hypertension, T2D - combined cases","description":"WTCCC genome-wide case-control association study using the cardiovascular disease CAD, HT and T2D as combined case collection and the 1958 British Birth Cohort and the UK National Blood Service collections as controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000006","title":"Genomewide Association Study of Inflammatory Bowel Disease","description":"WTCCC genome-wide case-control association study for Inflammatory Bowel Disease (IBD) using the 1958 British Birth Cohort and the UK National Blood Service collections as controls.      ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000007","title":"Genomewide Association Study of Inflammatory Bowel Disease - Combined Controls","description":"WTCCC genome-wide case-control association study for Inflammatory Bowel Disease (IBD) using six disease collections together with the 1958 British Birth Cohort and the UK National Blood Service collections as controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000008","title":"WTCCC case-control study for Inflammatory Bowel Disease, T1D and RA - combined cases","description":"WTCCC genome-wide case-control association study using three disease collections together with the 1958 British Birth Cohort and the UK National Blood Service collections as controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000009","title":"WTCCC case-control study for Hypertension","description":"WTCCC genome-wide case-control association study for Hypertension (HT) using the 1958 British Birth Cohort and the UK National Blood Service collections as controls.      ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000010","title":"WTCCC case-control study for Hypertension - Combined Controls","description":"WTCCC genome-wide case-control association study for Hypertension (HT) using six disease collections together with the 1958 British Birth Cohort and the UK National Blood Service collections as controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000011","title":"WTCCC case-control study for Rheumatoid Arthritis","description":"WTCCC genome-wide case-control association study for Rheumatoid Arthritis (RA) using the 1958 British Birth Cohort and the UK National Blood Service collections as controls.      ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000012","title":"WTCCC case-control study for Rheumatoid Arthritis - Combined Controls","description":"WTCCC genome-wide case-control association study for Rheumatoid Arthritis (RA) using six disease collections together with the 1958 British Birth Cohort and the UK National Blood Service collections as controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000013","title":"WTCCC case-control study for T1D and RA - combined cases","description":"WTCCC genome-wide case-control association study using two disease collections together with the 1958 British Birth Cohort and the UK National Blood Service collections as controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000014","title":"WTCCC case-control study for Type 1 Diabetes","description":"WTCCC genome-wide case-control association study for Type 1 Diabetes (T1D) using the 1958 British Birth Cohort and the UK National Blood Service collections as controls.      ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000015","title":"WTCCC case-control study for Type 1 Diabetes - Combined Controls","description":"WTCCC genome-wide case-control association study for Type 1 Diabetes (T1D) using six disease collections together with the 1958 British Birth Cohort and the UK National Blood Service collections as controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000016","title":"WTCCC case-control study for Type 2 Diabetes","description":"WTCCC genome-wide case-control association study for Type 2 Diabetes (T2D) using the 1958 British Birth Cohort and the UK National Blood Service collections as controls.      ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000017","title":"WTCCC case-control study for Type 2 Diabetes - Combined Controls","description":"WTCCC genome-wide case-control association study for Type 2 Diabetes (T2D) using six disease collections together with the 1958 British Birth Cohort and the UK National Blood Service collections as controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000018","title":"WTCCC case-control study for Ankylosing Spondylitis","description":"WTCCC genome-wide case-control association study for Ankylosing Spondylitis (AS) using the 1958 British Birth Cohort collection as controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000019","title":"WTCCC case-control study for Ankylosing Spondylitis - Combined Controls","description":"WTCCC genome-wide case-control association study for Ankylosing Spondylitis (AS) - Combined Controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000020","title":"WTCCC case-control study for Autoimmune Thyroid Disease","description":"WTCCC genome-wide case-control association study for Autoimmune Thyroid Disease (ATD) using the 1958 British Birth Cohort collection as controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000021","title":"WTCCC case-control study for Autoimmune Thyroid Disease - Combined Controls","description":"WTCCC genome-wide case-control association study for Autoimmune Thyroid Disease (ATD) - Combined Controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000022","title":"WTCCC case-control study for Multiple Sclerosis","description":"WTCCC genome-wide case-control association study for Multiple Sclerosis (MS) using the 1958 British Birth Cohort collection as controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000023","title":"WTCCC case-control study for Multiple Sclerosis - Combined controls","description":"WTCCC genome-wide accosication study for Multiple Sclerosis (MS) - Combined controls","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000024","title":"WTCCC case-control study for Breast cancer","description":"WTCCC genome-wide case-control association study for Breast cancer (BC) using the 1958 British Birth Cohort collection as controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000025","title":"WTCCC case-control study for Breast cancer - Combined Controls","description":"WTCCC genome-wide case-control association study for Breast cancer (BC) - Combined Controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000026","title":"MalariaGEN case-control study in the Gambia","description":"MalariaGEN case-control study in the Gambia.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000027","title":"WTCCC case-control study for Tuberculosis","description":"WTCCC genome-wide case-control association study for Tuberculosis (TB) using the African samples as controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000028","title":"WTCCC2 project controls - 1958 British Birth Cohort and National Blood Service","description":"WTCCC2 project controls - 1958 British Birth Cohort and National Blood Service","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000029","title":"Massive Genomic Rearrangment Acquired in a Single Catastrophic Event During Cancer Development","description":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina GA massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of 25 matched human renal cancer samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with renal cancer development.Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 25 renal cancers and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 50 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.\n                    ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000030","title":"Nordic Samples on build 36","description":"Nordic control dataset\n                    ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-02T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000031","title":"HLA has strongest association with IgA nephropathy in genome-wide analysis","description":"GWAS study of families with probands with IgA nephropathy from the UK Glomerulonephritis DNA bank\n                    ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000032","title":"Control sets genotyped with Dynal RELI SSO and Roche Molecular Systems platfroms","description":"HLA typing on subjects in WTCCC and T1DGC GWA studies using Dynal RELI SSO assays (Invitrogen, Paisley, UK), sequence-specific oligonucleotide probe-based method and  \n                        line strips from Roche Molecular Systems (Alameda, CA, USA)\n                    ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000033","title":"Geographical structure and differential natural selection among North European populations","description":"European populations and epidemiological cohorts are of special significance in the current era of genomic research aiming to characterize the background of common human diseases. The genome sequence, detailed information of genetic variations between individuals, high-throughput molecular technologies and novel statistical strategies create new possibilities to define genetic and life-style risk factors behind common health problems. Studies of large population cohorts are needed to transform the genetic information to detailed understanding of the predisposing factors in diseases affecting most human populations. European twin cohorts provide a unique competitive advantage for investigations of the role of genetics and environment or life style in the etiology of common diseases. This project will apply and develop new molecular and statistical strategies to analyze unique European twin and other population cohorts to define and characterise the genetic, environmental and life-style components in the background of health problems like obesity, migraine, coronary heart disease and stroke, representing major health care problems worldwide.\n                    ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000034","title":"\nGenome-wide association scan in Parkinson's disease\n                    ","description":"Genome-wide association scan was performed in 1,705 cases of parkinson's genotyped on the Illumina Human 660W SNP array, and 5,175 controls genotyped on the Illumina1.2M-Duo. Analysis was carried out on the overlaps set of SNPs.\n                    ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000036","title":"HLA-A*3101 and Carbamazepine-Induced Hypersensitivity Reactions in Europeans","description":"Based on the prior knowledge of involvement of the human leukocyte antigen locus in Han Chinese patients with carbamazepine-induced Stevens-Johnson syndrome, we imputed the HLA types for each case and control subject from the array of SNPs in the Human610-Quad GWAS platform (NCBI Build 36.1). We then performed a genome-wide association test which included the imputed HLA alleles as markers.\n                    ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000037","title":"Carbamazepine-induced hypersensitivity reactions in Europeans","description":"An antiepileptic drug carbamazepine is well tolerated by the majority of patients, but can cause severe and potentialy fatal hypersensitivity reactions in a small number of individuals. The aim of this study was to identify genetic predictors of hypersensitivity reactions to carbamazepine. We undertook a genome-wide association study (GWAS) in 22 patients of European ancestry with carbamazepine-induced hypersensitivity syndrome (HSS) and compared our data with genotypes from a healthy population within the WTCCC. We performed imputation of classical HLA alleles according to  a recently described method (Science. 2010 Dec 10;330(6010):1551-7. Epub 2010 Nov 4). GWAS statistical analysis was performed using logistic regression with an additive model of inheritance. \n                    ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000038","title":"T1DGC GWAS 1958 British Birth Cohort controls","description":"T1DGC genome-wide case-control association study for Type 1 Diabetes (T1D) using the 1958 British Birth Cohort as controls. The cases for this study are made available from the NCBI dbGAP.\n                    ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000039","title":"WTCCC3 case-control study for Primary Biliary Cirrhosis","description":"Genome-wide association scan was performed in 1,840 cases of primary biliary cirrhosis and 5,163 controls. Replication of new associations was tested in an independent set of 620 cases and 2,514 controls.\n                    ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000040","title":"Mutation of FOXL2 in granulosa cell tumors of the ovary","description":"We generated paired-end RNA-Seq data using the Illumina Genome Analyzer II platform for four adult granulosa cell tumours (GCTs) of the ovary (1 primary, 3 recurrent). We screened this data for the presence of GCT specific sequence variants and detected a non-synonymous mutation in the FOXL2 gene that was found to be recurrent in 97% of 89 additional GCTs.  To measure genomic stability of the four index cases, we generated Affmetrix SNP 6.0 data and analysed these data for copy number changes.  Raw sequence reads as well as Affymetrix CEL files are available to applicants.\n                    ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000043","title":"WNT-signaling and Dupuytren's Disease","description":"The EGA hosts the summary genotype results of the GWAS in 856 patients with Dupuytren's disease and 2,836 population based controls from 'LifeLines' cohort study\n","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000048","title":"A MITF germline mutation predisposes to melanoma and renal cell carcinoma","description":null,"abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000051","title":"A small cell lung cancer genome reports complex tobacco exposure signatures","description":"Cancer is driven by mutation. Worldwide, tobacco smoking is the major lifestyle exposure that causes cancer, exerting carcinogenicity through 60 chemicals that bind and mutate DNA. Using massively parallel sequencing technology, we sequenced a small cell lung cancer cell line, NCI-H209, to explore the mutational burden associated with tobacco smoking. 22,910 somatic substitutions were identified, including 132 in coding exons. Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context. Effects of transcription-coupled repair and a second, more general expression-linked repair pathway were evident. We identified a tandem duplication that duplicates exons 3-8 of CHD7 in-frame, and another two lines carrying PVT1-CHD7 fusion genes, suggesting that CHD7 may be recurrently rearranged in this disease. These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer.\n                    ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000052","title":"A Comprehensive Catalogue of Somatic Mutations from a Human Cancer Genome","description":"We have carried out complete sequencing of the genome of the human male maligant melanoma cell line COLO-829 using the Illumina Genome Analyzer II. We generated a sequencing library with a median insert size of ~200 bp following random fragmentation and gel fractionation of the genomic DNA. We sequenced 75 bases from both ends of these templates to cover the COLO-829 genome to an average depth of more than 40x. We have carried out purity-filtering (PF) to remove mixed reads, where two or more different template molecules are close enough on the surface of the flow-cell to form a mixed or overlapping cluster. No other filtering of the data has been carried out prior to submission. We have also submitted sequence data for a lymphoblastoid control cell line COLO-829BL from the same individual.\n                    ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000053","title":"Coeliac Disease Immunochip dataset","description":"Illumina Immunochip genotype data for coeliac disease and control samples. Data is in PLINK binary format. Calling algorithm for genotypes is based on GenomeStudio (GenTrain), with manual clustering of selected variants (please see published manuscript). Genotypes called in this way may not be exactly  identical to those generated by other algorithms - this is particularly relevant for groups wishing to utilise the control data (e.g. 1958 Birth Cohort). Please contact the investigators if you wish to discuss access to other data formats (e.g. .idat).\n                    ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000054","title":"Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution","description":"We have used next generation sequencing to sequence genomes (>43-fold coverage) and transcriptomes of an oestrogen-receptor-alpha-positive metastatic lobular breast cancer at depth. We found 32 somatic non-synonymous coding mutations present in the metastasis, and measured the frequency of these somatic mutations in DNA from the primary tumour of the same patient.\n                    ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000055","title":"Procardis study on novel susceptibility genes for coronary artery disease (CAD)","description":"An increased level of Lp(a) lipoprotein has been identified as a risk factor for coronary artery disease that is highly heritable. The genetic determinants of the Lp(a) lipoprotein level and their relevance for the risk of coronary disease are incompletely understood. METHODS: We used a novel gene chip containing 48,742 single-nucleotide polymorphisms (SNPs) in 2100 candidate genes to test for associations in 3145 case subjects with coronary disease and 3352 control subjects. Replication was tested in three independent populations involving 4846 additional case subjects with coronary disease and 4594 control subjects. RESULTS: Three chromosomal regions (6q26-27, 9p21, and 1p13) were strongly associated with the risk of coronary disease. The LPA locus on 6q26-27 encoding Lp(a) lipoprotein had the strongest association. We identified a common variant (rs10455872) at the LPA locus with an odds ratio for coronary disease of 1.70 (95% confidence interval [CI], 1.49 to 1.95) and another independent variant (rs3798220) with an odds ratio of 1.92 (95% CI, 1.48 to 2.49). Both variants were strongly associated with an increased level of Lp(a) lipoprotein, a reduced copy number in LPA (which determines the number of kringle IV-type 2 repeats), and a small Lp(a) lipoprotein size. Replication studies confirmed the effects of both variants on the Lp(a) lipoprotein level and the risk of coronary disease. A meta-analysis showed that with a genotype score involving both LPA SNPs, the odds ratios for coronary disease were 1.51 (95% CI, 1.38 to 1.66) for one variant and 2.57 (95% CI, 1.80 to 3.67) for two or more variants. After adjustment for the Lp(a) lipoprotein level, the association between the LPA genotype score and the risk of coronary disease was abolished. CONCLUSIONS: We identified two LPA variants that were strongly associated with both an increased level of Lp(a) lipoprotein and an increased risk of coronary disease. Our findings provide support for a causal role of Lp(a) lipoprotein in coronary disease.\n                    ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000056","title":"Identification of cis- and trans-regulatory variation modulating microRNA expression levels in human fibroblasts","description":"MicroRNAs (miRNAs) are regulatory noncoding RNAs that affect the production of a significant fraction of human mRNAs via post-transcriptional regulation. Interindividual variation of the miRNA expression levels is likely to influence the expression of miRNA target genes and may therefore contribute to phenotypic differences in humans, including susceptibility to common disorders. The extent to which miRNA levels are genetically controlled is largely unknown. In this report, we assayed the expression levels of miRNAs in primary fibroblasts from 180 European newborns of the GenCord project and performed association analysis to identify eQTLs (expression quantitative traits loci). We detected robust expression for 121 miRNAs out of 365 interrogated. We have identified significant cis- (10%) and trans- (11%) eQTLs. Furthermore, we detected one genomic locus (rs1522653) that influences the expression levels of five miRNAs, thus unraveling a novel mechanism for coregulation of miRNA expression","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000057","title":"Genome wide association study of Coeliac Disease","description":"We performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs with P(GWAS) < 10(-4) and 18 SNPs from 14 known loci in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome-wide significance (P(combined) < 5 x 10(-8)); most contain genes with immune functions (BACH2, CCR4, CD80, CIITA-SOCS1-CLEC16A, ICOSLG and ZMIZ1), with ETS1, RUNX3, THEMIS and TNFRSF14 having key roles in thymic T-cell selection. There was evidence to suggest associations for a further 13 regions. In an expression quantitative trait meta-analysis of 1,469 whole blood samples, 20 of 38 (52.6%) tested loci had celiac risk variants correlated (P < 0.0028, FDR 5%) with cis gene expression","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000059","title":"Assessment of genomic copy number alterations in breast cancer","description":"The aim of this study was to assess genomic copy number alterations in a panel of breast cancer cell lines.  These data were used to identify common aberrations associated with breast cancer, and also to identify aberrations associated with response to therapeutic compounds.\n                    ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000060","title":"A genome-wide meta analysis on stroke and ischemic stroke within four populations","description":"In this analysis a genome-wide meta-analysis was performed on all stroke and ischemic stroke.\n                    ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000062","title":"Complex Landscapes of Somatic Rearrangements in Human Breast Cancer Genomes","description":"We have used massively parallel paired end sequencing strategies to reconstruct the genomic landscape of 24 breast cancer genomes, through the identification and characterization of 2166 somatically acquired genomic rearrangements. These studies have revealed considerable complexity in the patterns of structural variation, identified novel fusion genes and unveiled new insights into the complex structure of amplicons.\n                    ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000064","title":"The patterns and dynamics of genomic instability in metastatic pancreatic cancer","description":"Pancreatic cancer is an aggressive malignancy with a five-year mortality of 97–98%, usually due to widespread metastatic disease. Previous studies indicate that this disease has a complex genomic landscape, with frequent copy number changes and point mutations, but genomic rearrangements have not been characterized in detail. Despite the clinical importance of metastasis, there remain fundamental questions about the clonal structures of metastatic tumours, including phylogenetic relationships among metastases, the scale of ongoing parallel evolution in metastatic and primary sites, and how the tumour disseminates. Here we harness advances in DNA sequencing to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. We find that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, namely dysregulated G1-to-S-phase transition with intact G2–M checkpoint. These initiate amplification of cancer genes and occur predominantly in early cancer development rather than the later stages of the disease. Genomic instability frequently persists after cancer dissemination, resulting in ongoing, parallel and even convergent evolution among different metastases. We find evidence that there is genetic heterogeneity among metastasis-initiating cells, that seeding metastasis may require driver mutations beyond those required for primary tumours, and that phylogenetic trees across metastases show organ-specific branches. These data attest to the richness of genetic variation in cancer, brought about by the tandem forces of genomic instability and evolutionary selection.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000074","title":"Evolution of an adenomacarcinoma in response to selection by targeted kinase inhibitors","description":"Background - Adenocarcinomas of the tongue are rare and represent the minority (20-25%) of salivary gland tumors affecting the tongue.  We investigated the utility of massively parallel sequencing to characterize an adenocarcinoma of the tongue, before and after treatment. \n                        Results - In the pre-treatment tumor we identified 7,629 genes within regions of copy number gain. 1,078 genes exhibited increased expression relative to the blood and unrelated tumors and four genes contained somatic protein-coding mutations. Our analysis suggested the tumor cells were driven by the RET oncogene. Genes whose protein products are targeted by the RET inhibitors sunitinib and sorafenib correlated with being amplified and or highly expressed. Consistent with our observations administration of sunitinib was associated with stable disease lasting 4 months, after which the lung lesions began to grow.  Administration of sorafenib and sulindac provided disease stabilization for an additional 3 months after which the cancer progressed and new lesions appeared. A recurring metastasis possessed 7,288 genes within copy number amplicons, 385 genes exhibiting increased expression relative to other tumours and 9 new somatic protein coding mutations. The observed mutations and amplif\n                        ications were  consistent with therapeutic resistance arising through activation of the MAPK and AKT pathways. Conclusions - We conclude that complete genomic characterization of a rare tumour has the potential to aid in clinical decision making and identifying therapeutic approaches where no established treatment protocols exist.  These results also provide direct in-vivo genomic evidence for mutational evolution within a tumor under drug selection and potential mechanisms of drug resistance accrual.\n                    ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000075","title":"ARID1A Mutations in Endometriosis-Associated Ovarian Carcinomas","description":"We have sequenced the whole transcriptomes of 18 ovarian clear-cell carcinomas and 1 ovarian clear-cell carcinoma cell line and found somatic mutations in ARID1A (the AT-rich interactive domain 1A [SWI-like] gene) in 6 of the samples. ARID1A encodes BAF250a, a key component of the SWI–SNF chromatin remodeling complex. We sequenced ARID1A in an additional 210 ovarian carcinomas and a second ovarian clear-cell carcinoma cell line and measured BAF250a expression by means of immunohistochemical analysis in an additional 455 ovarian carcinomas","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000077","title":"A Large-Scale, Consortium-Based Genomewide Association Study of Asthma","description":"We carried out a genomewide association study by genotyping 10,365 persons with physician-diagnosed asthma and 16,110 unaffected persons, all of whom were matched for ancestry. We used random-effects pooled analysis to test for association in the overall study population and in subgroups of subjects with childhood-onset asthma (defined as asthma developing before 16 years of age), later-onset asthma, severe asthma, and occupational asthma.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-24T01:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000082","title":"ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium.","description":"The telomeric amplicon at 8p12 is common in oestrogen receptor-positive (ER+) breast cancers. Array-CGH and expression analyses of 1172 primary breast tumours revealed that ZNF703 was the single gene within the minimal amplicon and was amplified predominantly in the Luminal B subtype. Amplification was shown to correlate with increased gene and protein expression and was associated with a distinct expression signature and poor clinical outcome. ZNF703 transformed NIH 3T3 fibroblasts, behaving as a classical oncogene, and regulated proliferation in human luminal breast cancer cell lines and immortalized human mammary epithelial cells. Manipulation of ZNF703 expression in the luminal MCF7 cell line modified the effects of TGFβ on proliferation. Overexpression of ZNF703 in normal human breast epithelial cells enhanced the frequency of in vitro colony-forming cells from luminal progenitors. Taken together, these data strongly point to ZNF703 as a novel oncogene in Luminal B breast cancer.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-04T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000083","title":"METABRIC","description":"The elucidation of breast cancer subgroups and their molecular drivers\nrequires integrated views of the genome and transcriptome from\nrepresentative numbers of patients. We present an integrated analysis of\ncopy number and gene expression in a discovery and validation\nset of 997 and 995 primary breast tumours, respectively, with long-term\nclinical follow-up. Inherited variants (CNVs, SNPs) and acquired somatic\ncopy number aberrations (CNAs) were associated with expression in  40% of\ngenes, although the landscape was dominated by cis and trans-acting CNAs. By\ndelineating expression outlier genes driven in cis by CNAs, we identified\nputative cancer genes, including deletions in PPP2R2A, MTAP, and MAP2K4.\nUnsupervised analysis of paired DNA/RNA profiles revealed novel subgroups\nwith distinct clinical outcomes, which reproduced in the validation cohort.\nThese include a high-risk, ER-positive 11q13/14 cis-acting subgroup and a\nfavourable prognosis subgroup devoid of CNAs. Trans-acting aberration\n0152hotspots were found to modulate subgroup-specific gene networks, including\na TCR deletion-mediated adaptive immune response in the 0152CNA-devoid\nsub-group and a Basal-specific chromosome 5 deletion-driven mitotic network.\nOur results provide a novel molecular stratification of the breast cancer\npopulation, derived from the impact of somatic copy number aberrations on\nthe transcriptome.","abstract":"The elucidation of breast cancer subgroups and their molecular drivers\nrequires integrated views of the genome and transcriptome from\nrepresentative numbers of patients. We present an integrated analysis of\ncopy number and gene expression in a discovery and validation\nset of 997 and 995 primary breast tumours, respectively, with long-term\nclinical follow-up. Inherited variants (CNVs, SNPs) and acquired somatic\ncopy number aberrations (CNAs) were associated with expression in  40% of\ngenes, although the landscape was dominated by cis and trans-acting CNAs. By\ndelineating expression outlier genes driven in cis by CNAs, we identified\nputative cancer genes, including deletions in PPP2R2A, MTAP, and MAP2K4.\nUnsupervised analysis of paired DNA/RNA profiles revealed novel subgroups\nwith distinct clinical outcomes, which reproduced in the validation cohort.\nThese include a high-risk, ER-positive 11q13/14 cis-acting subgroup and a\nfavourable prognosis subgroup devoid of CNAs. Trans-acting aberration\n0152hotspots were found to modulate subgroup-specific gene networks, including\na TCR deletion-mediated adaptive immune response in the 0152CNA-devoid\nsub-group and a Basal-specific chromosome 5 deletion-driven mitotic network.\nOur results provide a novel molecular stratification of the breast cancer\npopulation, derived from the impact of somatic copy number aberrations on\nthe transcriptome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000084","title":"WTCCC2 case-control study for Ulcerative Colitis","description":"WTCCC2 project genome-wide case-control association study for Ulcerative Colitis (UC) using the 1958 British Birth Cohort and the UK National Blood Service collections as controls.      ","abstract":"GWAS UC Publication","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000086","title":"An immune response network associated with blood lipid levels","description":"Genome-wide genotyping was performed on a population-based cohort from the capital region of Finland using the Illumina 610-Quad SNP microarray","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000087","title":"Genome-wide association study of severe malaria in Gambian mother-father-child trios","description":"Genome-wide association study of severe malaria in Gambian mother-father-child trios","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000088","title":"Genome-wide association study of severe malaria in Ghanain mother-farther-child trios","description":"Genome-wide association study of severe malaria in Ghanain mother-farther-child trios","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000092","title":"CLL Genome","description":"The Chronic Lymphocytic Leukemia (CLL) Genome Project aims to identify genetic alterations involved in the development and progression of the CLL, which are still unknown, with the objective of generating a comprehensive catalogue of genetic alterations in 500 independent tumours. The CLL Genome Project, as a contributing member of the International Cancer Genome Consortium (ICGC), has the purposes of creating diagnostic tools, discovering therapeutic targets and developing new strategies that will allow a customized therapy for CLL in order to make it more precise and effective. This study consists of two datasets. EGAD00001000023 described in the Nature paper (2011), Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia, and the dataset EGA00001000044 & & EGAD00001000083 described in the Nature (2011) paper, Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia.Additional data generated within the ICGC-CLL genome project can be found in studies EGAS00001000374 and EGAS00001001306","abstract":"The Chronic Lymphocytic Leukemia (CLL) Genome Project aims to identify genetic alterations involved in the development and progression of the CLL, which are still unknown, with the objective of generating a comprehensive catalogue of genetic alterations in 500 independent tumours. The CLL Genome Project, as a contributing member of the International Cancer Genome Consortium (ICGC), has the purposes of creating diagnostic tools, discovering therapeutic targets and developing new strategies that will allow a customized therapy for CLL in order to make it more precise and effective.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000097","title":"Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP \n ","description":"We conducted GWAS of sporadic CJD, variant CJD, iatrogenic CJD, inherited prion disease, kuru and resistance to kuru despite attendance at mortuary feasts. After quality control we analysed 2000 samples and 6015 control individuals (provided by the Wellcome Trust Case Control Consortium and KORA-gen), for 491032-511862 SNPs in the European study. Association studies were done in each geographical and aetiological group followed by several combined analyses. \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000098","title":"METABRIC","description":"Solid tumors are complex tissues composed of a mixture of cancer and normal cells, which complicates the interpretation of their molecular profiles. Normal cell contamination can dilute cancer cell information and tissue architecture is generally not reflected in molecular assays. To address these challenges, we developed a computational approach based on standard Haematoxylin and Eosin-stained sections and demonstrated its power in a discovery cohort of  323 breast tumors and an independent validation cohort of 241 tumors. First, to deconvolute cellular heterogeneity and detect subtle genomic aberrations, we introduced an algorithm  based on tumor cellularity to increase the comparability of copy-number profiles between samples. Second, we demonstrated that a predictor for survival integrating image-based and molecular features significantly outperforms classifiers based on single data types. Third, we described and validated a novel, independent prognostic factor based on quantitative analysis of spatial patterns between stromal cells, which are not detectable by molecular assays. Our quantitative methods refine and complement molecular assays of tumor samples and could benefit all large-scale cancer studies.First, to deconvolute cellular heterogeneity and detect subtle genomic aberrations, we introduced an algorithm  based on tumor cellularity to increase the comparability of copy-number profiles between samples. Second, we demonstrated that a predictor for survival integrating image-based and molecular features significantly outperforms classifiers based on single data types. Third, we described and validated a novel, independent prognostic factor based on quantitative analysis of spatial patterns between stromal cells, which are not detectable by molecular assays. Our quantitative methods refine and complement molecular assays of tumor samples and could benefit all large-scale cancer studies.\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000099","title":"Identification of genetic etiology of CAMRQ2","description":"We aimed to identify genetic etiology of cerebellar ataxia, mental retardation, and disequilibrium syndrome (CAMRQ). Targeted sequencing of the entire CAMRQ2 locus, 7.1 Mb interval on chromosome 17p13, in three affected individuals and two obligate carriers uncovered the mutation associated with CAMRQ2.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000101","title":"The Genetic Analysis of multiple sclerosis","description":"We created these data in order to identify genetic variants associated with increased susceptibility to multiple sclerosis. Cases from many parts of the world were genotyped with the Illumina 660 chip along with Swedish controls. In our analysis we also used control data from the WTCCC2 common UK controls and from other published studies.\n                    ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000102","title":"Molecular Phenotyping to Accelerate Genomic Epidemiology (MolPAGE)","description":"MolPAGE is an integrated EU project that aims to develop methods and tools for discovery of biomarkers associated with diabetes (see www.ocdem.ox.ac.uk for MolOBB and www.twinsuk.ac.uk for MolTWIN).","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000103","title":"WTCCC2 Ischaemic Stroke study","description":"Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke\n                    ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000104","title":"Genomewide association studies in ankylosing spondylitis","description":"The aim of this study was to identify genes associated with ankylosing spondylitis susceptibility in British and Australian individuals of European descent.\n \n \n \n \n \n \n \n \n \n \n \n \n ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000105","title":"Copy number analysis of Diamond-Blackfan Anemia (DBA) using SNP array","description":"Diamond–Blackfan anemia (DBA), is a rare congenital anemia that usually presents in infancy. About fifty percent of DBA patients possess mutations in ribosomal protains (RPs). In this study, we performed genomic copy number analysis using SNP arrays for 27 Japanese DBA patients to detect genomic copy number lesions of the RP genes' loci.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000108","title":"Genome-wide association scan in psoriasis","description":"To identify novel susceptibility loci for psoriasis, we undertook a genome-wide association scan of of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000109","title":"Genetics of gene expression in primary human immune cells \n ","description":"The purpose of this study was to identify cell specific expression quantitative trait loci in freshly isolated highly purified primary B-cells and monocytes from healthy subjects of European ancestry. Cells were purified from Ficoll gradient prepared peripheral blood mononuclear cell fractions using positive selection via magnetic bead labelling of the B-cell marker CD19 and monocyte marker CD14. RNA was extracted from 287 B-cell samples and 288 monocyte samples. RNA was then hybridised to HumanHT-12 v4 BeadChips whole genome expression arrays (Illumina). Individuals were genotyped on HumanOmniExpress-12v1.0 BeadChips (Illumina) at 733202 genetic markers. Data presented include the raw expression values and Robust Spline Normalised values (RSN) for expression for each cell type per individual. Additional genotype data per individual is available on request.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000114","title":"Krakow experiment - Northern Finland Birth Cohort 1966","description":null,"abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000115","title":"Association studies using the Metabochip array - Samples analysed by the WTCCC (1958 British Birth Cohort (58BC), Hypertension cohort (HT), Type 2 Diabetes Cohort (T2D) and Coronary Artery Disease (CAD) cohort)","description":"Genomewide association studies (GWAS) have proven a powerful hypothesis-free method to identify common disease-associated variants. Even quite large GWAS, however, have only at best identified moderate proportions of the genetic variants contributing to disease heritability. To provide cost-effective genotyping of common and rare variants to map the remaining heritability and to fine-map established loci, the Metabochip Consortium has developed a 200,000 SNP chip that has been produced in very large numbers for a fraction of the cost of GWAS chips. This chip provides a powerful tool for genetic studies of metabolic, cardiovascular and anthropometric traits (Voight et al., in press PLoS Genetics).","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000116","title":"Molecular Sub-grouping of CNS-PNET","description":"In our study we aimed to define CNS-PNET subgroups.  We performed Expression, Genotyping and/or Immunohistochemistry on 142 samples from 20 worldwide centers.  Using these techniques, we have identified three molecular subgroups with distinct expression and copy number patterns, as well as, unique clinical characteristics.  Specifically, these molecular subgroups were distinguished by primitive neural (group 1), oligoneural (group 2), and mesenchymal lineage (group 3) gene-expression signatures with differential expression of cell-lineage markers LIN28 and OLIG2.  Our report underscores the importance of concerted, collaborative efforts to study large retrospective cohorts of tumours and patients to accelerate biological and ultimately therapeutic studies of rare tumours. The outcome of such a collaboration allowed us to identify LIN28 and OLIG2  as promising diagnostic and prognostic molecular markers for CNS PNET that warrant further assessment in prospective clinical trials.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000118","title":"WTCCC2 Schizophrenia study","description":"A WTCCC2 project genome-wide case-control association study for schizophrenia (SP) in individuals from Ireland.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000119","title":"Powerful Identification of Cis-regulatory SNPs in Human Primary Monocytes Using Allele-Specific Gene Expression","description":" The aim of this study was to compare the power to detect associations between SNPs using cis-eQTL mapping and ASE analysis (allele specific expression). ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-04T01:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000120","title":"Integrated Genetic and Epigenetic Analysis of Childhood ALL Reveals a Synergistic Role for Structural and Epigenetic Lesions In Determining Disease Phenotype","description":"Acute lymphoblastic leukemia (ALL), the commonest childhood malignancy, is characterized by recurring gross and submicroscopic structural genetic alterations that contribute to leukemogenesis. Disordered epigenetic regulation is a hallmark of many tumors, and while analysis of DNA methylation of limited numbers of genes or ALL samples suggests epigenetic alterations may also be important, a large-scale integrative genome-wide analysis evaluating DNA methylation in ALL has not been performed. Here, we report an integrated epigenomic, transcriptional and genetic analysis of 167 childhood ALL cases, comprising B-progenitor ALL with hyperdiploidy (N=26), ETV6-RUNX1 (N=27), TCF3-PBX1 (N=9), BCR-ABL1 (N=19), rearrangement of MLL (MLLr) (N=20), rearrangement of CRLF2 (N=11, CRLF2r), deletion of ERG (N=11), miscellaneous or normal karyotype (N=14), and T-lineage ALL (N=30), including 4 MLLr cases and 7 cases with early T-cell precursor immunophenotype. Genome-wide profiling of structural DNA alterations was performed for all cases using Affymetrix 500K and SNP 6.0 arrays. Affymetrix U133A gene expression profiling data was available for 154 cases. Genome-wide methylation profiling was performed using the HELP microarray assay, which measures methylation at approximately 50,000 CpGs distributed among 22,722 Refseq promoters. Methylation data was compared to that of normal pro-B (CD34+CD19+sIg-), pre-B (CD34-CD19+sIg-) and mature B (CD34-CD19+sIg+) cells FACS-sorted from bone marrow of 6 healthy individuals. Unsupervised hierarchical clustering of the top 4043 most variable methylation probesets identified 9 B-ALL clusters with significant correlation to specific genetic lesions including ETV6-RUNX1, MLLr, BCR-ABL1, CRLF2r, TCF3-PBX1 and ERG deletion.  T-ALLs and hyperdiploid B-ALLs also defined specific DNA methylation clusters.  Supervised analysis including limma and ANOVA identified distinct DNA methylation signatures for each subtype. Notably, the strength of these signatures was subtype dependent, with more differentially methylated genes observed in ALL cases with genetic alterations targeting transcriptional regulators (e.g. ETV6-RUNX1 and MLLr) and fewer genes in cases with alterations deregulating cytokine receptor signaling (e.g. CRLF2r). Aberrant DNA methylation affected specific and distinct biological processes in the various leukemia subtypes implicating epigenetic regulation of these pathways in the pathogenesis of these different forms of ALL (e.g. TGFB and TNF in ERG deleted leukemias; telomere and centriole regulation in BCR-ABL1 ALL).  Aberrantly methylated genes were also enriched for binding sites of known or suspected oncogenic transcription factors that might represent cooperative influences in establishing the phenotype of the various B-ALL subtypes. Most importantly, an integrated analysis of methylation and gene expression of these ALL subtypes demonstrated striking inversely correlated expression of the corresponding gene transcripts.   The methylation signatures of each subtype exhibited only partial overlap with those of normal B cells, indicating that the signatures do not simply reflect stage of lymphoid maturation. In a separate approach, we discovered that 81 genes showed consistent aberrant methylation across all ALL subtypes, including the tumor suppressor PDZD2, HOXA5, HOXA6 and MSH2. Inverse correlation with expression was confirmed in 66% of these genes.  These data suggest the existence of a common epigenetic pathway underlying the malignant transformation of lymphoid precursor cells. Integrative genetic and epigenetic analysis revealed hypermethylation of genes on trisomic chromosomes that do not show increased expression, suggesting that epigenetic silencing may control genes within amplified regions and explain why only selected genes are overexpressed. Finally, analysis of individual genes targeted by recurring copy number alterations in ALL revealed a subset of genes also targeted by abnormal methylation, with corresponding changes in gene expression (e.g. ERG, GAB1), suggesting that such genes are inactivated far more frequently than suggested by genetic analyses alone.  Collectively, the data support a key role of epigenetic gene regulation in the pathogenesis of ALL, and point towards a scenario where genetic and epigenetic lesions cooperatively determine disease phenotype.\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00000000121","title":"WTCCC2 Pharmacogenomic Response to Statins study","description":"A WTCCC2 project genome-wide study for pharmacogenomic response to statins (PR) in individuals from Scotland.\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000122","title":"METABRIC miRNA landscape","description":"MicroRNAs (miRNAs) are key players in cancer pathogenesis1. They display differential expression across breast cancer subtypes, and play oncogenic and tumor-suppressive roles2-6. A systematic study of the global miRNA landscape in breast cancer and the factors shaping it has not been undertaken. Here we report the results of profiling miRNA expression in 1,302 breast tumors with detailed clinical annotation and long-term follow-up, and for which matching genomic and mRNA expression data were available7. This provides a comprehensive view of the quantity, distribution and variation of the miRNA population and dissects how much genomic, transcriptional and post-transcriptional events contribute to miRNA expression architecture. The key clinical parameters and cellular pathways related to the miRNA landscape are identified, exemplified by context-dependent interaction with cell adhesion and Wnt signaling. Strikingly, in breast cancer miRNAs appear to act as modulators of mRNA-mRNA interactions rather than molecular switches. We demonstrate an important modulatory role for miRNAs in the biology of breast tumors devoid of somatic copy number aberrations, a common subtype where immune response is prominent. Remarkably, prognostic miRNA signatures derived in this subtype are consistently prognostic across several other subtypes and validate in external cohorts. These findings represent a new framework to study the biology of miRNA in human cancer.\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000129","title":"The complex SNP and CNV genetic architecture of the increased risk of  congenital heart defects in Down syndrome ","description":"Here we aimed to contribute to the description of the genetic architecture of Congenital heart defect (CHD) in Down syndrome (DS), and report the results of a genome-wide association study using samples from DS individuals with and without CHD. CHD is a common developmental defect of DS occurring in 40% of cases. This case-control GWAS includes 187 DS with CHD as cases, and 151 DS without CHD as controls.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000131","title":"Comparison of the performance of two commercial genome-wide association study genotyping platforms in Han Chinese Samples","description":"Affymetrix 6.0, Illumina OMNIExpress, and llumina Immunochip genotype data for Han Chinese population including rheumatoid arthritis cases and controls. Data is in PLINK binary format. Illumina genotype clustering was performed using Illumina’s BeadStudio software. SNPs were reclustered using the study samples, low quality subjects were removed, and a subset of clustering results were manually inspected and verified. All SNPs with GenCall scores less than 0.15 were excluded. For Affymetrix chips, clustering was performed using the program Birdseed version 2, as implemented using Affymetrix Genotyper Console v4.0, using the default quality control (QC) thresholds.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000132","title":"The Haemgen RBC study","description":"Anaemia is a major determinant of global ill-health. To refine our understanding of the genetic factors influencing red blood cell formation and function, we carried out a meta-analysis of genome-wide association studies (GWAS) for six red blood cell traits: haemoglobin (HB), mean cell haemoglobin (MCH), mean cell haemoglobin concentration (MCHC), mean cell volume (MCV), packed cell volume (PCV) and red blood cell count (RBC). We provide genome-wide association results for 62,553 people of European ancestry using up to 2,644,161 autosomal SNPs. Participants with extreme measurements (>+/-3SD from mean) were excluded on a per phenotype basis. Imputation was done using haplotypes from HapMap Phase 2. SNP associations with each phenotype were tested by linear regression using an additive genetic model. Associations were tested separately in each cohort, with principal components and other study specific factors as covariates to account of population substructure. We then carried out meta-analysis of results from the individual cohorts using z-scores weighted by square root of sample size. SNPs with MAF<1% (weighted average across cohorts) were removed, as were SNPs with weight <50% of phenotype sample size.  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  Anaemia is a major determinant of global ill-health. To refine our understanding of the genetic factors influencing red blood cell formation and function, we carried out a meta-analysis of genome-wide association studies (GWAS) for six red blood cell traits: haemoglobin (HB), mean cell haemoglobin (MCH), mean cell haemoglobin concentration (MCHC), mean cell volume (MCV), packed cell volume (PCV) and red blood cell count (RBC). We provide genome-wide association results for 62,553 people of European ancestry using up to 2,644,161 autosomal SNPs. Participants with extreme measurements (>+/-3SD from mean) were excluded on a per phenotype basis. Imputation was done using haplotypes from HapMap Phase 2. SNP associations with each phenotype were tested by linear regression using an additive genetic model. Associations were tested separately in each cohort, with principal components and other study specific factors as covariates to account of population substructure. We then carried out meta-analysis of results from the individual cohorts using z-scores weighted by square root of sample size. SNPs with MAF<1% (weighted average across cohorts) were removed, as were SNPs with weight <50% of phenotype sample size.  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00000000134","title":"NOWAC blood-based breast cancer case-control study","description":"Tumor-host interactions extend beyond the local microenvironment and cancer development largely depends on the ability of malignant cells to hijack and exploit the normal physiological processes of the host. Although abnormalities in a host’s systemic immunity are associated with increased cancer susceptibility, the functional interplay between tumor cells and circulating immune cells in regulating tumorigenic responses is unclear. We employed the Norwegian Women and Cancer study, a large prospective population-based cohort study, to identify gene expression changes in blood cells that provide a robust and reproducible diagnostic signal specific to breast cancer patients. We further show that circulating blood cells in breast cancer patients are enriched in genes involved in systemic immunosuppression and the motility, metabolism, growth, and proliferation of immune cells. By mining of the cancer-associated blood transcriptome, we identified immune mediators or biomarkers that could permit early detection of breast cancer and open avenues to novel targeted immunotherapies.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000135","title":"Genome-wide differential DNA methylation signatures in pediatric acute\nlymphoblastic leukemia","description":"The aim of our study is to provide a comprehensive analysis of DNA methylation in a large collection of primary pediatric acute lymphoblastic leukemia (ALL) samples taken at diagnosis and relapse of the disease as well as non-leukemic control blood cells from healthy individuals. Complementary gene expression data available at the Gene Expression Omnibus under series GSE26878.  \n  \n  \n  \n  ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00000000137","title":"MRCA and MRCE SNP genotypes","description":"Gene expression levels can be an important link DNA between variation and phenotypic manifestations. Our previous map of global gene expression based on approximately 400K SNPs and 50K transcripts in 400 sib pairs from the MRCA family panel has been widely used to interpret the results of GWAS. Here, we more than double the size of our initial dataset with expression data on 550 additional individuals from the MRCE family panel using the Illumina whole genome expression array. We have used new statistical methods for dimension reduction to account for non-genetic effects in estimates of expression levels and we have also included SNPs imputed from the 1000 Genomes Project. Our methods reduced false discovery rates and increased the number of eQTLs mapped either locally or at a distance (i.e. in cis or trans) from 1,534 in the MRCA dataset to 4,452 (with <5% FDR). Imputation of 1000 Genomes SNPs further increased the number of eQTLs to 7,302. Using the same methods and imputed SNPs in the newly acquired MRCE dataset we identified eQTLs for 9000 genes. The combined results identify strong local and distant effects for transcripts from 14,177 genes. Our eQTL database (http://www.hsph.harvard.edu/faculty/liming-liang/software/eqtl/) based on these results is freely available to help define the function of disease-associated variants.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-20T01:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS0000000122","title":"METABRIC miRNA landscape","description":"MicroRNAs (miRNAs) are key players in cancer pathogenesis1. They display differential expression across breast cancer subtypes, and play oncogenic and tumor-suppressive roles2-6. A systematic study of the global miRNA landscape in breast cancer and the factors shaping it has not been undertaken. Here we report the results of profiling miRNA expression in 1,302 breast tumors with detailed clinical annotation and long-term follow-up, and for which matching genomic and mRNA expression data were available7. This provides a comprehensive view of the quantity, distribution and variation of the miRNA population and dissects how much genomic, transcriptional and post-transcriptional events contribute to miRNA expression architecture. The key clinical parameters and cellular pathways related to the miRNA landscape are identified, exemplified by context-dependent interaction with cell adhesion and Wnt signaling. Strikingly, in breast cancer miRNAs appear to act as modulators of mRNA-mRNA interactions rather than molecular switches. We demonstrate an important modulatory role for miRNAs in the biology of breast tumors devoid of somatic copy number aberrations, a common subtype where immune response is prominent. Remarkably, prognostic miRNA signatures derived in this subtype are consistently prognostic across several other subtypes and validate in external cohorts. These findings represent a new framework to study the biology of miRNA in human cancer.\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n ","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000000","title":"fc_coating_study","description":"R&amp;D","abstract":"R&amp;D flowcell study","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000001","title":"Exome Resequencing of Progressive Hearing Loss","description":"Exome resequencing of progressive hearing loss.","abstract":"Exome resequencing of progressive hearing loss.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-13T01:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000002","title":"Breast Cancer Follow Up Series","description":"This study's purpose is to use data generated in whole genome and exome Breast Cancer sequencing to target specific areas in multiple other Breast Cancer samples. These areas will then be subjected to PCR in multiple cases, tagged and then pool the resultant amplicons. These amplicons will then be sequenced on the Illumina GAII. This is hoped to show the prevalence of previous findings in multiple individuals in a high throughput method.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000003","title":"Cancer Single Cell Sequencing","description":"This study is to ascertain whether it is feasible to extract a single cell form a Cancer cell line, amplify it and sequence it.","abstract":"This study is to ascertain whether it is feasible to extract a single cell form a Cancer cell line, amplify it and sequence it.","study_type":"Other","pubmed_ids":[21248752],"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000004","title":"Multifocal_Breast_Project","description":"Comparison of genomic rearrangements and DNA methylationpatterns between different foci of multiple synchronous(multifocal and multicentric) invasive breast cancers","abstract":"Multiple (multifocal/multicentric) breast carcinomas, especially when occurring in thesame breast, represent a real challenge for both pathologists and clinicians in terms ofidentifying the cellular origin and the best therapeutic management of the cancer. Thequestion whether multifocal/multicentric carcinomas are due to the spread of a singlecarcinoma throughout the breast or is due to multiple carcinomas arising simultaneously hasbeen a matter of debate. Until now, only small studies have compared different histologicaland molecular characteristics in multifocal/multicentric tumors. Based on their results, somesupport the fact that the synchronous tumors are a clonal proliferation of a single mammarycarcinoma, whereas others suggest that multifocal/multicentric might be multiple synchronousprimary tumors. However, none of those projects have given a detailed characterization ofmulticentric/multifocal tumors. In this project we will therefore for the first time comparegenomic rearrangements and DNA methylation patterns between different foci in a limitednumber of multiple synchronous (multifocal and multicentric) invasive breast cancers. Withthis work, we therefore hope to provide some evidence whether or not each focus matters inmultifocal and multicentric breast cancer to define the adequate therapeutic approach,especially in the context of targeted therapies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000005","title":"Lung_Rearrangement_Study","description":"Genomic libraries (500 bps) will be generated from total genomic DNA derived from cancer samples and subjected to 37 bp, paired end sequencing on the llumina GA. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemias, lymphomas and soft tissue tumors. However, conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution. We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000006","title":"Renal_Cancer_Exome_Sequencing","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 25 renal cancers and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 50 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina GA massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of 25 matched human renal cancer samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with renal cancer development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000007","title":"i_seq_profiling_and_the_control_of_VSG_expression_site_silencing_in_trypanosomes","description":"Random fragments of t. brucei DNA gets inserted into an expression vector, where they gets expressed and the RNA knocks out genes. We're using a TraDIS-like approach to identify the sequences.","abstract":"We have combined 10x genome-coverage, inducible RNA interference libraries with massive-parallel, next-generation sequencing to assign knock-down associated ‘fitness scores’ to &gt;7000 genes in the parasitic African trypanosome, Trypanosoma brucei. This interference-sequencing (i-seq) approach typically reveals &gt;2000 genes associated with significant and semi-quantitative loss-of-fitness. Applied to libraries differentiated from the bloodstream to the insect-stage, i-seq profiling indicates a major shift from over-dependence on the nuclear and flagellum proteomes to over-dependence on the mitochondrial and trans-membrane proteomes. The profile associated with differentiation itself broadly mirrors the insect-stage profile. In addition, RNA-binding factors are significantly over-represented as ‘core essential functions’ reflecting the mRNA regulatory requirements associated with constitutive polycistronic transcription. A key virulence mechanism in the bloodstream is antigenic variation, involving monoallelic Variant Surface Glycoprotein (VSG) expression-site transcription in an extranucleolar RNA polymerase I compartment and strict silencing of thousands of other sub-telomeric VSGs 1. Using the i-seq data-set, we identify a chromatin chaperone (CAF-1) and a histone deacetylase (DAC3) required for VSG expression-site silencing. Thus, i-seq profiling reveals the genes and associated profiles underlying unique trypanosomatid biology.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000008","title":"Whole_Genome_Sequencing_of_hiPS_cells","description":"Human induced pluripotent stem (hiPS) cells hold great promise for regenerative medicine. Safety issues of use of hiPS cells however remain to be addressed. One of such issues is mutations derived from somatic donor cells and introduced during genome manipulation. We sequence whole genomes of hiPS cells and analyzed mutations. Our study brings hiPS cell technology one step closer to application to regenerative medicine.","abstract":"Human induced pluripotent stem (hiPS) cells hold great promise for regenerative medicine. Safety issues of use of hiPS cells however remain to be addressed. One of such issues is mutations derived from somatic donor cells and introduced during genome manipulation. We sequence whole genomes of hiPS cells and analyzed mutations. Our study brings hiPS cell technology one step closer to application to regenerative medicine.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000009","title":"SCLC","description":"The aim of this study is to use sequence data generated from 500 bp paired end reads using the Illumina platform to characterise the breakpoints of chromosomal translocations, amplifications and deletions at high resolution (to the bp).","abstract":"Cancer is driven by mutation. Using Illumina GA massively parallel sequencing technology, we aim to sequence matched human cancer samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer development.","study_type":"Synthetic Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000010","title":"MPD_Exome_Sequencing","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 50 Myeloproliferative disease samples and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 100 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina GA massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of 50 matched human  Myeloproliferative disease samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with  Myeloproliferative disease development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000011","title":"CLL_cancer_Sample_Sequencing","description":"Genomic libraries (500 bps) will be generated from  total genomic DNA derived from CLL cancer samples and subjected to total of eight lanes of 37 bp, paired end sequencing on the llumina GA. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemias, lymphomas and soft tissue tumors. However, conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution, thus the role of genomic rearrangement in human CLL cancer is unknown. We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting breast cancer genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000012","title":"Various_Cancer_Fusion_Gene_Sequencing","description":"Genomic libraries (500 bps) will be generated from  total genomic DNA derived from 50 commomon epithelial cancer samples and subjected to total of eight lanes of 37 bp, paired end sequencing on the llumina GA. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemias, lymphomas and soft tissue tumors. However, conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution, thus the role of genomic rearrangement in common epithelial cancer is unknown. We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting common epithelial cancer genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000013","title":"Osteosarcoma_Sequencing","description":"Genomic libraries (500 bps) will be generated from  total genomic DNA derived from 25 osetocarcinoma samples and subjected to total of three lanes of 37 bp paired end sequencing on the llumina GA per sample. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemia's, lymphomas and soft tissue tumors. However, conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution, thus the role of genomic rearrangement in human osetosarcomas is unknown. We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting ovarian cancer genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000014","title":"CLL_Cancer_Whole_Genome_Sequencing","description":"Genomic libraries (500 bps) will be generated from  total genomic DNA derived from a range of cancer samples and subjected paired end sequencing on the llumina GA. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The aim of this project is to identify the somatic mutations and hence the genes involved in the development of chronic lymphocytic leukemia critical through the sequencing of chronic lymphocytic leukemia cancer genomes and normal DNAs from the same individuals.  Tumour DNA will be analysed and compared to matching constitutional (normal) DNA from the same patient to identify tumour-acquired (somatic) alterations. These alterations (mutations, copy number alterations, translocations and other  genomic aberrations) will be identified in multiple tumours and then these sets will be compared against each other to determine which genes are mutated in common and which pathways have been targeted","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000015","title":"FAIRE_Seq_in_blood_cells","description":"Genome-wide association studies (GWAS) have identified loci harbouring common genetic variants associated with diseases, including coronary artery disease (CAD) and its main complication, myocardial infarction (MI). These loci have usually small effects, whereas the underlying causative variant(s) remain typically unknown. In parallel, GWAS on quantitative haematological traits, e.g. the count and volume of blood cells, have started to shed some light on the biological processes through which such disease-associated loci are likely to act.As most association signals are intra- or intergenic, causal variants are likely to impact regulation of gene expression. Our aim is to map regulatory elements at loci associated with CAD/MI and blood traits to aid the identification of functional variants.We will perform FAIRE (formaldehyde-assisted isolation of regulatory elements), a robust method for identifying accessible chromatin and regulatory regions in human chromatin, in combination with next-generation sequencing technology to map regulatory elements in primary human megakaryocytes, erythrocytes, monocytes, and potentially haematopoietic stem cells (CD34+). In the first pilot we are going to analyse 3 individuals requesting up to 16 lanesThis project is in collaboration with the Department of Haematology (University of Cambridge) within the Bloodomics2/NetSim consortium. Cell culture work will be performed at the Blood Centre, whereas FAIRE, DNA sequencing, and data analysis will be conducted at the Sanger Institute.","abstract":"Genome-wide association studies (GWAS) have identified loci harbouring common genetic variants associated with diseases, including coronary artery disease (CAD) and its main complication, myocardial infarction (MI). These loci have usually small effects, whereas the underlying causative variant(s) remain typically unknown. In parallel, GWAS on quantitative haematological traits, e.g. the count and volume of blood cells, have started to shed some light on the biological processes through which such disease-associated loci are likely to act.As most association signals are intra- or intergenic, causal variants are likely to impact regulation of gene expression. Our aim is to map regulatory elements at loci associated with CAD/MI and blood traits to aid the identification of functional variants.We will perform FAIRE (formaldehyde-assisted isolation of regulatory elements), a robust method for identifying accessible chromatin and regulatory regions in human chromatin, in combination with next-generation sequencing technology to map regulatory elements in primary human megakaryocytes, erythrocytes, monocytes, and potentially haematopoietic stem cells (CD34+). In the first pilot we are going to analyse 3 individuals requesting up to 16 lanesThis project is in collaboration with the Department of Haematology (University of Cambridge) within the Bloodomics2/NetSim consortium. Cell culture work will be performed at the Blood Centre, whereas FAIRE, DNA sequencing, and data analysis will be conducted at the Sanger Institute.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000016","title":"The_GENCODE_exome___sequencing_the_complete_human_exome","description":"We report the design of an extended set of targets for capturing the complete human exome, based on annotation from the GENCODE consortium. The extended set covers an addition 5,594 genes and 10.3 Mb compared to current sets which mainly target the CCDS database. The additional regions include potential disease genes previously inaccessible to exome resequencing studies, such as 43 genes linked to ion channel activity and 70 genes linked to protein kinase activity. In total, the new GENCODE exome set developed covers 47.9Mb and performed well in sequence capture experiments with HapMap and clinical samples. Samples within this study are prepared with either the CCDS or GENCODE exome products.","abstract":"We report the design of an extended set of targets for capturing the complete human exome, based on annotation from the GENCODE consortium. The extended set covers an addition 5,594 genes and 10.3 Mb compared to current sets which mainly target the CCDS database. The additional regions include potential disease genes previously inaccessible to exome resequencing studies, such as 43 genes linked to ion channel activity and 70 genes linked to protein kinase activity. In total, the new GENCODE exome set developed covers 47.9Mb and performed well in sequence capture experiments with HapMap and clinical samples. Samples within this study are prepared with either the CCDS or GENCODE exome products.","study_type":"Exome Sequencing","pubmed_ids":[21364695],"external_links":null,"is_released":true,"released_date":"2015-05-27T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000017","title":"Familial Melanoma Sequencing","description":"In this experiment we have sequenced the exome of 15 individuals from eight families who have familial melanoma. By sequencing the exome we hope to be able to identify new genes that are associated with this disease.","abstract":"In this experiment we have sequenced the exome of 15 individuals from eight families who have familial melanoma. By sequencing the exome we hope to be able to identify new genes that are associated with this disease.","study_type":"Exome Sequencing","pubmed_ids":[24686849],"external_links":null,"is_released":true,"released_date":"2011-01-01T00:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000018","title":"ChIP_Seq_of_different_histone_modifications_in_human_primary_megakaryocytes_and_erythroblasts_and_in_a_human_megakaryocytic_cell_line__CHRF__","description":"Study of the transcription factor NF-E2 important for hematopoiesis in human megakaryocytes and erythroblasts as well as study of histone marks in human megakaryocytic and erythroblastic cells and cell lines.","abstract":"Study of the transcription factor NF-E2 important for hematopoiesis in human megakaryocytes and erythroblasts as well as study of histone marks in human megakaryocytic and erythroblastic cells and cell lines.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000019","title":"Paired_end_sequencing_of_human_chromosome_21_from_Tc1_mouse","description":"The TC1 Down Syndrome mouse model carries a human chromosome 21. O’Donelly et al (2005) reported this chromosome was deleted in the process of establishing the mouse model. The status of the Hsa21 was described as, 42Mb (90%) of the complete 46.9Mb was present. Subsequent microarray analysis of genomic DNA from this mouse revealed the Hsa21 was more highly rearranged and in addition to deletions the mouse had 5 duplicated regions. The aim of this project was to establish the content of the human chromosome 21 in the TC1 Down Syndrome mouse model with respect to copy number variation, chromosome rearrangements and mutations. Five Illumina paired-end libraries have been produced and sequenced from the following DNA samples together with their library insert sizes: Sample name: Tc1_21, Input DNA:Flow sorted chr 21, library insert size: 200bp.   Sample name: Tc1_21_500, Input DNA: Flow sorted chr 21, library insert size: 500bp.        Sample name: Tc1_4kb_insert, Input DNA: Tc1 +ve mouse genomic DNA, library insert size: 4kb.                Sample name: TC1genomicDNA, Input DNA: Tc1 +ve mouse genomic DNA, library insert size: 500bp.        Sample name: TC14kb insert genomicDNA, Input DNA: Tc1 +ve mouse genomic DNA, library insert size: 4kb.","abstract":"Tc1 mice are a mouse model for Down Syndrome; the mice carry a copy of human chromosome 21. Recent array CGH experiments have shown that the human chromosome 21 is not intact and regions are in fact deleted and duplicated. To establish the structure and composition of the human chromosome 21 in Tc1 mice we have flow sorted the chromosome, made small and large insert paired-end libraries and sequenced the libraries. The sequence data has been mapped back to human chromosome 21 sequence and the mouse genome. The sequence data has been analysed for copy number information and the aberrant mapping paired end reads have been interrogated to real the structure of the chromosome.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000020","title":"Genetic_variation_in_Kuusamo","description":"The aim of this study is to characterize as completely as possible the genetic variation and structure of Kuusamo and surrounding regions. We will perform low coverage, whole genome sequencing in a relatively limited number (approximately 200) of individuals from the FINRISK study both of whose parents are born in Kuusamo, Posio or Taivalkoski. Sequencing will be performed at the Wellcome Trust Sanger Institute (WTSI). We have previously shown using simulations and genome wide SNP data that the genetic characteristics agree with known genealogical data, and that approximately 200 individuals suffice to capture the majority of the genetic variation in this population.We have also developed methods for long-range haplotyping and long-range imputation, which are more accurate than traditional methods. This will allow us to identify a majority of the founder haplotypes in this population. The information from the haplotypes identified in this study can be used in other studies to impute from genome-wide SNP data the full genome sequence of samples ascertained for specific phenotypes.","abstract":"In this study, we aim to fully characterize a very high proportion of the genetic variation in a population. Information obtained from this study can be used  by imputation in other studies aiming to identify genetic risk factors for disorders in the same population.  It will also serve as a proof-of-principle study and allow method development for other similar projects in the future involving sequencing of other population isolates.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-25T01:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000021","title":"Adenoid_Cystic_Carcinoma_sequencing_project","description":"Genomic libraries (500 bps) will be generated from  total genomic DNA derived from 25 adenoid cystic carcinoma samples and subjected to total of eight lanes of 37 bp, paired end sequencing on the llumina GA. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemias, lymphomas and soft tissue tumors. However, conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution, thus the role of genomic rearrangement in human adenoid cystic carcinoma is unknown. We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting adenoid cystic carcinoma genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000022","title":"Methylome_ALSPAC___Pilot","description":"In the GSC meeting of 12 Feb 2009 a project wasproposed that was part of a collaboration with ALSPAC to look atmethylation in the ALSPAC cohort. The decision of the committee at thetime was that Aarno and others should pilot the technology needed tostudy the methylome before approving the large-scaleproject. Sequencing the methylome was subsequenctly discussed by theBOM at the beginning of this year and it was suggested that a pilotshould go ahead and the need for a pipeline for methylome sequencingwould be revisited at the end of this year when there were data tolook at. In light of these decisions we are proposing a pilot projectto sequence the methylome in 4 ALSPAC samples using MeDIPseq. If thepilot is successful we will submit a follow-up re-application for theproject that was originally submitted in Febraury 2009 (to sequencethe methylome in 20 individuals from the ALSPAC cohort whom have hadsamples taken at 3 different time points , 10 with a regular BMI, and10 with a high BMI to establish whether PBL DNA methylation patternsdiffer between the obese and non-obese individuals and ifinter-individual changes over time in DNA methylation can be detcetdin PBL DNA) . The MeDIPseq for the pilot will be performed and fundedfrom within Aarno Palotie's faculty team. Funding sort for sequencingonly. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"In the GSC meeting of 12 Feb 2009 a project was proposed that was part of a collaboration with ALSPAC to look at methylation in the ALSPAC cohort. The decision of the committee at the time was that Aarno and others should pilot the technology needed to study the methylome before approving the large-scale project. Sequencing the methylome was subsequenctly discussed by the BOM at the beginning of this year and it was suggested that a pilot should go ahead and the need for a pipeline for methylome sequencing would be revisited at the end of this year when there were data to look at. In light of these decisions we are proposing a pilot project to sequence the methylome in 4 ALSPAC samples using MeDIPseq. If the pilot is successful we will submit a follow-up re-application for the project that was originally submitted in Febraury 2009 (to sequence the methylome in 20 individuals from the ALSPAC cohort whom have had samples taken at 3 different time points , 10 with a regular BMI, and 10 with a high BMI to establish whether PBL DNA methylation patterns differ between the obese and non-obese individuals and if inter-individual changes over time in DNA methylation can be detcetd in PBL DNA) . The MeDIPseq for the pilot will be performed and funded from within Aarno Palotie's faculty team. Funding sort for sequencing only.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000023","title":"Identifying autosomal recessive mutations causing neurological disorders","description":"The objective of this study is to resequence of targeted intervals containing autosomal recessive variants causing neurological disorders in consanguineous pedigrees. Using homozygosity mapping, three intervals of very different sizes have previously been unambiguously mapped for three different neurological diseases: 2.4Mb, 8Mb and 14.3Mb in size, for Microlissencephaly, Severe Mental Retardation and Complicated hereditary spastic paraplegia respectively. This study is a pilot to assess how well custom targeted resequencing performs across a broad size range of intervals. The study design is to use a different custom capture probe set for each interval, pulldown from a single patient from each family, and sequence 1 lane using Illumina paired-reads for each sample. Candidate variants will be followed up in the families themselves, and in patients with similar phenotypes from outbred populations.","abstract":"The objective of this study is to resequence of targeted intervals containing autosomal recessive variants causing neurological disorders in consanguineous pedigrees. Using homozygosity mapping, three intervals of very different sizes have previously been unambiguously mapped for three different neurological diseases: 2.4Mb, 8Mb and 14.3Mb in size, for Microlissencephaly, Severe Mental Retardation and Complicated hereditary spastic paraplegia respectively. This study is a pilot to assess how well custom targeted resequencing performs across a broad size range of intervals. The study design is to use a different custom capture probe set for each interval, pulldown from a single patient from each family, and sequence 1 lane using Illumina paired-reads for each sample. Candidate variants will be followed up in the families themselves, and in patients with similar phenotypes from outbred populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-11T16:12:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000024","title":"Piloting exome resequencing in consanguineous families with homozygosity mapping intervals","description":"This pilot study aims to generate pilot data to inform future study designs in consanguineous families or inbred populations by resequencing the exome of six individuals from five families with neurodevelopmental diseases. For all of these families a single mapping interval containing the causal variant has previously been identified.","abstract":"Multiple neurodevelopmental disease loci have been mapped in consanguineous families and inbred populations to single mapping intervals with very strong LOD score support. Here we propose to exome sequence six individuals from five families with neurodevelopmental diseases, as positive controls to illustrate the power of exome sequencing smaller consanguineous families where homozygosity mapping cannot unambiguously localise a single mapping interval. The five loci have been chosen to represent a reasonably broad phenotype spectrum and considerable variation in numbers of genes within the mapping interval. On the basis of existing exome data we would predict that exome sequencing two affected sibs from a consanguineous (first-cousin marriage) family should narrow the causal variants down to ~10 homozygous novel functional variants, and that subsequent follow-up in additional relatives (e.g. affected or unaffected sibs), and functional considerations, should rapidly identify the causal locus. If true, this would change the typical study designs used for mapping disease genes in consanguineous families, however, pilot data is needed to confirm the power of this approach. This project entails the generation and analysis of 6 exomes sequenced to ~50X mean depth.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-11T17:23:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000025","title":"Whole_exome_sequencing_of_Severe_Insulin_Resistant_patients_","description":"Illumina paired-end sequencing of whole- exome pulldown DNA from Severe Insulin Resistant patients.","abstract":"Over the last 10 years or so candidate gene re-sequencing in individuals with severe insulin resistance syndromes has led to the discovery of genes (e.g. INSR, LMNA, PPARG, AKT2, PPP1R3, CIDEC, AS160, etc)  that when mutated are causative of those particular phenotypes. However, many insulin resistant patients exist for whom the underlying causative mutation(s) remains unknown.  We have initiated a study targeted at re-sequencing the whole exome in a subset of individuals selected on the basis of their phenotype and likely mode of inheritance in an attempt to identify additional likely causal variants.  Candidate causal variants will be confirmed by follow-up co-segregation analysis in affected families and further analysis in additional cases and/or downstream functional and clinical follow up.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-12T12:42:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000026","title":"Whole_Exome_Sequencing_for_Characterization_of_Disease_Causing_Mutations_in_two_Pakistani_Families_Suffering_from_Autosomal_Recessive_Ocular_Disorders_","description":"We propose to use whole exome Agilent solutionprobes and paired end Illumina sequencing to sequence 4 individualsfrom two families suffering from novel autosomal recessive disease[microphthalmia, MOP (OMIM %251600) and non-syndromic persistenthyperplastic primary vitreous, PHPV (OMIM %611311)]. Selectedcandidate variants will subsequently be genotyped in the remainingfamily members in Pakistan with the aim of identifying the rarehomozygous recessive mutations responsible for the disease phenotype.  This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Since 1996 Prof. S. Qasim Mehdis group in Pakistan has identified several large consanguineous Pakistani families with rare non-syndromic Mendelian eye disorders. We propose to sequence four individuals (an affected child and unaffected parent each) from two families with novel disease phenotypes [microphthalmia, MOP (OMIM %251600) and non-syndromic persistent hyperplastic primary vitreous, PHPV (OMIM %611311)]. The aim is to identify the causative rare homozygous recessive mutations in the patients that are not in the reference sequence and for which the unaffected parent is expected to be heterozygous. Variants thus identified will be ranked based upon the available expression data and predictions of their consequences. Selected candidate variants will be genotyped in all family members in Pakistan in order to identify the one best associated with the disease phenotype.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-12T13:42:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000027","title":"TMD_AMLK_Exome_Study","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 20 Primary Acute Megakaryocytic Leukemia samples and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 100 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina GA massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of 20 matched human Acute Megakaryocytic Leukemia (AMKL) disease samples from Downs patiens with previous Transient Myeloproliferative Disease (TMD). Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with the progression of Downs TMD to AMKL.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-17T10:34:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000028","title":"PV_Exome_Study","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 50 Polycythemia Vera Myeloproliferative Disease  samples and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 100 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina GA massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of 50 matched human Polycythemia Vera Myeloproliferative disease samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with Myeloproliferative disease development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-01-17T10:37:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000029","title":"Sequencing_component_for_the_whole_genome_methylation_analysis_in_PBMC_s_and_cell_subsets__pilot_study_","description":"Background: DNA methylation has been shown to play a major role in determining cellular phenotype by regulating gene expression. Moreover, dysregulation of differentially methylated genes has been implicated in disease pathogenesis of various conditions including cancer development as well as autoimmune diseases such as systemic Lupus erythematosus and rheumatoid arthritis. Evidence is rapidly accumulating for a role of DNA methylation in regulating immune responses in health and disease. However, exact mechanisms remain unknown.Aims: The aim of this pilot study is to perform whole genome methylation analysis in peripheral blood mononuclear cells (PBMCs) and cell subsets (CD4, CD8, CD14, CD19, CD16 and whole PBMCs) obtained from 6 healthy volunteers. Additionally, mRNA expression arrays will be performed in order to correlate DNA methylation with gene expression. Methods: DNA+RNA was extracted simultaneously (AllPrep kit, QIAGEN) from all cell subsets. Whole genome methylation analysis will be preformed using two methodological approaches: a) Infinium Methylation Bead Array K450 (Illumina) and b) MeDIP-seq. Sample details: Genomic DNA (in water) PBMCs (and cell subsets) extracted from 6 healthy volunteers. CD4, CD8, CD14, CD19, CD16, whole PBMCs. Total number of samples: 6","abstract":"Background: DNA methylation has been shown to play a major role in determining cellular phenotype by regulating gene expression. Moreover, dysregulation of differentially methylated genes has been implicated in disease pathogenesis of various conditions including cancer development as well as autoimmune diseases such as systemic Lupus erythematosus and rheumatoid arthritis. Evidence is rapidly accumulating for a role of DNA methylation in regulating immune responses in health and disease. However, exact mechanisms remain unknown.Aims: The aim of this pilot study is to perform whole genome methylation analysis in peripheral blood mononuclear cells (PBMCs) and cell subsets (CD4, CD8, CD14, CD19, CD16 and whole PBMCs) obtained from 6 healthy volunteers. Additionally, mRNA expression arrays will be performed in order to correlate DNA methylation with gene expression. Methods: DNA+RNA was extracted simultaneously (AllPrep kit, QIAGEN) from all cell subsets. Whole genome methylation analysis will be preformed using two methodological approaches: a) Infinium Methylation Bead Array K450 (Illumina) and b) MeDIP-seq. Sample details: Genomic DNA (in water) PBMCs (and cell subsets) extracted from 6 healthy volunteers. CD4, CD8, CD14, CD19, CD16, whole PBMCs. Total number of samples: 6","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000030","title":"ADCC_Rearrangement_Screen","description":"Genomic libraries (500 bps) will be generated from  total genomic DNA derived from 25 adenoid cystic carcinoma samples and subjected to total of eight lanes of 37 bp, paired end sequencing on the llumina GA. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemias, lymphomas and soft tissue tumors. However, conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution, thus the role of genomic rearrangement in human adenoid cystic carcinoma is unknown. We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting adenoid cystic carcinoma genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-02-02T12:44:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000031","title":"Matched_breast_cancer_fusion_gene_study","description":"Genomic libraries (500 bps) will be generated from  total genomic DNA derived from 40 breast cancer samples and subjected to total of eight lanes of 37 bp, paired end sequencing on the llumina GA. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemias, lymphomas and soft tissue tumors. However, conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution, thus the role of genomic rearrangement in human breast cancer is unknown. We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting breast cancer genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-02-07T11:22:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000032","title":"Kaposi_sarcoma_exome","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from Kaposi sarcoma cancer and matched normal DNA from the same patients. Next Generation sequencing will be performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of a number of matched human Kaposi sarcoma samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-02-07T11:42:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000033","title":"1__Fanconi_Anemia_transformation_to_AML","description":"Genomic libraries (500 bps) will be generated from total genomic DNA derived from 7 Fanconi anemia (FA) derived Acute myeloid leukemia samples and subjected to total of two lanes of 50 bp, paired end sequencing on the llumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. In hematological malignancies the majority of known human cancer genes are somatically rearranged. Conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution. We aim to use massively parallel paired end sequencing to characterise the occurrence of critical genomic rearrangements for Fanconi Anemia progression to AML, understand the clonal evolution of those and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-02-14T13:11:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000034","title":"MDSMPN_Rearrangement_Screen","description":"Genomic libraries (500 bps) will be generated from total genomic DNA derived from 11 Myelodysplastic Myeloproliferative neoplasms (MDSMPN) and subjected to total of two lanes of 50 bp, paired end sequencing on the llumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. In hematological malignancies the majority of known human cancer genes are somatically rearranged. Conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution. We aim to use massively parallel paired end sequencing to characterise the occurrence of critical genomic rearrangements for a range of MDS MPN subtypes, understand the clonal evolution of those and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-02-14T13:15:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000035","title":"Sequencing_Acute_Myeloid_Leukaemia_","description":"This project will aim at sequencing and analysing three samples from a patient with acute myeloid leukaemia (AML) with t(15;17) translocation (acute promyelocytic leukaemia). The patient was treated with standard chemotherapy and samples (blood and bone marrow) taken for minimal residual disease measured during and after chemotherapy.  2-3years later the patient presented a second AML containing inv (16).In this project we will sequence both AML and normal genomes to find associated mutations This will allow unprecedented insights into the dynamics of appearance of secondary AML, since we will be able to use the MRD samples to track the emergence of the inv(16) leukaemia. We will also be able to distinguish whether the 2 leukaemias are clonally related or not. This project will entail sequencing and analysis of three samples (whole genome 30x coverage) using Hi-Seq. The funds from this grant will cover the cost of sequencing 9 lanes from the AML t(15;17) sample, 9 lanes from AML inv(16) sample and 8 lanes from the normal genome.","abstract":"This project will aim at sequencing and analysing three samples from a patient with acute myeloid leukaemia (AML) with t(15;17) translocation (acute promyelocytic leukaemia). The patient was treated with standard chemotherapy and samples (blood and bone marrow) taken for minimal residual disease measured during and after chemotherapy.  2-3years later the patient presented a second AML containing inv (16).In this project we will sequence both AML and normal genomes to find associated mutations This will allow unprecedented insights into the dynamics of appearance of secondary AML, since we will be able to use the MRD samples to track the emergence of the inv(16) leukaemia. We will also be able to distinguish whether the 2 leukaemias are clonally related or not. This project will entail sequencing and analysis of three samples (whole genome 30x coverage) using Hi-Seq. The funds from this grant will cover the cost of sequencing 9 lanes from the AML t(15;17) sample, 9 lanes from AML inv(16) sample and 8 lanes from the normal genome","study_type":"Synthetic Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-02-18T10:09:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000036","title":"Integrative_Oncogenomics_of_Multiple_Myeloma","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from Multiple Myeloma patient DNA and matched normal DNA from the same patients. Two lanes of Illumina GA sequencing will be performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina GA massively parallel sequencing technology, we aim to sequence microRNAs plus the protein coding genome of matched human cancer samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give insights into mutational processes, cellular repair pathways and gene networks associated with cancer development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-03-01T11:23:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000037","title":"Gastric_and_Esophageal_tumour_rearrangement_screen","description":"Genomic libraries (500 bps) will be generated from total genomic DNA derived from gastric and esophageal tumours and subjected to total of two lanes of 50 bp, paired end sequencing on the llumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution. We aim to use massively parallel paired end sequencing to characterise the occurrence of critical genomic rearrangements and understand the clonal evolution of cancer and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-03-03T15:36:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000038","title":"Chondrosarcoma_Exome_","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from Chondrosarcoma cancer and matched normal DNA from the same patients. Next Generation sequencing will be performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina massively parallel sequencing technology, we aim to sequence microRNAs plus the protein coding genome of a number of matched human Chondrosarcoma samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-03-15T13:55:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000039","title":"Methylation_analysis_in_GM01240___GM01247","description":"Aim: We aim to compare current (MeDIP-seq), new (Illumina Infinium 450K BeadChip) and future (PacBio) methods for whole genome DNA methylation analysis. As the interest in determination of disease methylation profiles increases, the scope, advantages and limitations of these methods requires assessment. There are key questions to answer and specific challenges to overcome. For example, how much detail/resolution is sufficient to identify regions of differential methylation and regions of biological/medical significance within a sample? How much coverage of the genome is required for accurate methylation analysis? Is it important to confirm which regions of the genome are unmethylated in addition to focusing on those that are methylated? Loss of methylation may be of equal importance within the cell since this may also contribute to disease pathogenesis. A multi-method (affinity enrichment/bisulphite-conversion based/direct sequencing of methyl-cytosine) and technology platform (Illumina HiSeq/PacBio/Illumina Infinium BeadChip) comparison will enable us to determine the strengths and weakness of each method. We propose to compare four methods using two DNA samples from the Coriell Institute for Cell Repository to assess both current and future capabilities for whole genome methylation analysis in parallel: A) MeDIP-seq using Illumina HiSeq B) Illumina Infinium HumanMethylation 450K BeadChip and C) whole genome methylation sequencing using PacBio. Existing single molecule deep bisulphite sequencing data generated previously from these same samples at the WTSI for targeted regions (30-40 genes) on the human X chromosome will be used to assess performance of each method. The methods selected for this study will generate data covering a range of resolutions from a whole genome scan to array (target defined) resolution and up to single base pair, single molecule resolution; the highest level of detail possible with methods currently available.Samples: DNA from sibling pair GM01240 (female) and GM01240 (male).Requirements: Both samples will be analysed using;A.MeDIP-seq using Illumina HiSeq (one HiSeq lane, 75bp paired end, per sample)B.Illumina Infinium HumanMethylation 450K BeadChipWe are expecting a potentially unnecessary high coverage using one HiSeq lane per sample. However, for the MeDIP procedure we do not have a multiplexing procedure in place. Our requirements for PacBio sequencing have been discussed with and will be supported by the Sequencing Technology Development group.","abstract":"DNA methylation is one of the most studied epigenetic marks in the human genome, with the result that the desire to map the human methylome has driven the development of several methods to map DNA methylation on a genomic scale. Our study presents the first comparison of two of these techniques - the targeted approach of the Infinium HumanMethylation450 BeadChip with the immunoprecipitation and sequencing-based method, MeDIP-seq. Both methods were initially validated with respect to bisulfite sequencing as the gold standard and then assessed in terms of coverage, resolution and accuracy. The two methods were compared using DNA from two cell lines: GM01240 (XX) and GM01247 (XY), a sibling pair of European descent. The regions of the methylome that can be assayed by both methods and those that can only be assayed by one method were determined and the discovery of differentially methylated regions (DMRs) by both techniques was examined. Our results show that the Infinium HumanMethylation450 BeadChip and MeDIP-seq show a good positive correlation (Spearman correlation of 0.68) on a genome-wide scale and can both be used successfully to determine differentially methylated loci in RefSeq genes, CpG islands, shores and shelves. MeDIP-seq however, allows a wider interrogation of methylated regions of the human genome, including thousands of non-RefSeq genes and repetitive elements, all of which may be of importance in disease. In our study MeDIP-seq allowed the detection of 15,709 differentially methylated regions, nearly twice as many as the array-based method (8070), which may result in a more comprehensive study of the methylome.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000040","title":"Exome sequencing of hyperplastic polyposis patients","description":"In this project we are sequencing the exomes of patients with hyperplastic polyposis, and tumours from these patients.","abstract":"Hyperplastic polyposis may be a familial condition resulting in the formation of hyperplastic lesions of the gastrointestinal tract. In this study we will sequence the exomes (germline) of patients with hyperplastic polyposis and also tumors from these patients. The aim of this sequencing is to identify genes that predispose to this disorder and also to determine the somatic mutations that contribute to cancer development in this condition.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-03-17T11:58:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000041","title":"Disorders_of_growth_and_insulin_action_","description":"Illumina paired-end sequencing of whole- exome pulldown DNA from Severe Insulin Resistant patients.","abstract":"Over the last 10 years or so, candidate gene re-sequencing in individuals with severe insulin resistance has led to the discovery of genes that when mutated are causative of those particular phenotypes.  With the development of new sequencing technology, sequencing all exons in the genome has become possible.  This has enabled us, in collaboration with Steve O’Rahilly, Rob Semple and David Savage, to investigate disorders of insulin action in patients for whom the underlying causative mutation(s) remain unknown.  Here, we have sequenced three samples from two individuals with unusual phenotypes.  Two of these samples are from the same individual showing massive leg overgrowth paired with a lean upper body, we have therefore, taken samples from both the affected leg and the unaffected arm, in order to make a comparison.  The third sample is from an individual with less severe insulin resistance, but a proinsulin processing defect resulting in raised split Pro-insulin.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-03-17T16:23:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000042","title":"HER2_positive_Breast_Cancer_","description":"We propose to definitively characterise the somatic genetics of HER2+ve breast cancer through generation of comprehensive catalogues of somatic mutations in a number of cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-03-18T13:35:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000043","title":"Investigating_low_frequency_variants_in_CAD_MI_cases__controls_and_pedigrees_using_whole_exome_sequencing_and_custom_pulldowns","description":"The Cardiogenics re-sequencing study will consist of three parts: Eight pools of 25 individuals will be sequenced using a Nimblegen hybrid-capture solution specific to miRNA sequences, 80 pools of 25 individuals will be sequenced using a custom Agilent SureSelect array covering genes associated with coronary artery disease (CAD) and myocardial infarction (MI), 10 individuals from families with a history of CAD/MI will be exome sequenced using the Sanger exome array. The experiment will use the early onset patients from the German MI cohort and the UK BHF CAD/MI cohort both of which have strong family history. For controls we will consider individuals from the UKBS and KORA cohorts.","abstract":"In rare cases, coronary artery disease (CAD) and myocardial infarction (MI) appear to be inherited in an autosomal-dominant mode. Cardiogenics has access to 19 multi-generation families (max. 27 MI patients per family) displaying an autosomal dominant inheritance pattern for  severe CAD / MI using systematic large scale screening.  Linkage analyses in these families have revealed so far a limited number of peacks and only in one instance  two families with the same linkage peak  on chromosome 8q. Resequencing of biological candidates in this large interval has not yield any mutations so far. We propose to sequnce the exome of 10 affected individuals one per family and include the two families with the 8q linakge. We anticipate genotyping interesting variants in all family membersIn Cardiogenics the recent meta-analyses of GWAS studies under the CARDIOGRAM umbrella has identified several new loci reaching genome wide significance with several more currently under replication. We anticipate that upon completion of the replication phase of CARDIOGRAM we will have close to 30 CAD/MI confirmed loci. We want to investigate the presence or absence of high penetrance, low frequency variants in these confirmed regions of association focusing initially on exonic sequences that are more likely to harbor. In addition, functional annotation of variants outside coding regions is not yet available. As CAD/MI is currently not scheduled within WTCCC+ Cardiogenics want to proceed with the experiment using the same design of resequencing up to 1000 cases and 1000 controls in pools of 25 individuals. The experiment will use the early onset patients from the German MI cohort and the UK BHF CAD/MI cohort both of which have strong family history and together total over 5000 cases. For controls we will consider individuals from the UKBS and KORA cohorts. We will use the recently installed Syzygy software for calling variants from these pools. Variants that are functionally important and show strong enrichment in the case vs control pools will be considered for follow up by genotyping  in 8K + 8K cases/controlsMicro RNA (miRNA) sequences have recently been found to have a profound impact on complex disease, however, so far, no study has investigated these sequences in association with CAD and MI. We have designed a solution hybrid capture array that is targeted to known miRNA sites, in order to find high penetrance rare variants in these regions. We will sequence 4 pools of case and and 4 pools of controls from the above-mentined UK and German collections.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-03-22T12:05:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000044","title":"Identification_and_functional_validation_of_driver_mutations_in_colorectal_cancer","description":"Targeted exome sequencing of human colorectal cancers for the identification of novel cancer drivers.","abstract":"In this experiment we sequenced the exons of a selected set of genes in sporadic human colorectal cancers. These genes were selected based on the frequency of their mutation in a transposon screen performed in the mouse intestine. The rationale for this experiment was to validated genes identified in the mouse as cancer driver genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-03-23T11:41:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000045","title":"RS_sequencing_of_S_pull_449_87","description":"RS sequencing of S.pull 449/87","abstract":"RS sequencing of S.pull 449/87","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000046","title":"Mutational_Screening_of_Human_Acute_Myleloid_Leukaemia_Samples","description":"Characterization of somatic mutations in Acute Myeloid Leukaemia samples to identify whether they can be classified into three mutually exclusive groups.","abstract":"Acute myeloid leukaemia (AML) is an aggressive and molecularly diverse disease with a poor overall survival of 15-25%1. With an annual incidence of 2.9 per 100,000, AML is currently the commonest myeloid malignancy in Europe2, yet the two main therapeutic options for this disease, anthracyclines and purine analogues, have remained unchanged for over 20 years3. Therapeutic advances rely heavily on an improved understanding of the molecular pathogenesis of AML and the development of rationally designed treatments.AML is divided into cytogenetic subgroups, each with its own molecular characteristics, prognostic features and responsiveness to treatment1. The largest and most molecularly diverse subgroup is AML with a normal karyotype (AML-NK) which constitutes 45% of all cases. The molecular lesions underlying this disease have been obscure until recently. However, a large number of molecular lesions have been identified in the last few years4-7 and although it is not clear how many of these mutations operate theories about the pathogenesis of AML-NK are being formulated.Earlier this year some of these mutations were studied for co-occurrence in individual cases of AML-NK were8. The results were interpreted as supporting the premise that somatic mutations in AML-NK can be grouped into 4 groups, and that mutations from within each group do not co-occur in the same AML whilst mutations from different groups complement each other. No conclusions were drawn with regards to the the nature of this mutual exclusivity. However, a very recent publication from a whole genome sequencing study which described a new type of mutation in the gene for the DNA methyltransferase DNMT3A, throws new light into the pathogenesis of AML-NK and suggests that mutations in this disease could be bundled into 3 groups with each group representing complementary molecular mechanism","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-04-01T10:59:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000047","title":"Whole Exome Sequencing of Permanent Neonatal Diabetes Patients","description":"Whole Exome Sequencing of Permanent Neonatal Diabetes Patients","abstract":"Permanent Neonatal Diabetes (PND) is defined by chronic hyperglicaemia due to non autoimmune severe insulin deficiency. Over the last few years candidate gene re-sequencing of individuals with this particular phenotype has identified three genes causative of PND: KCNJ11, ABCC8 and INS.  However about 20% to 30% of PND cases do not have a genetic cause identified.We initiated a whole exome re-sequencing study of families selected on the basis of their specific phenotype with the aim to identify variants causative of PND. We selected a subset of patients for their clinical status and excluded the presence of mutations in the three genes known to be causative of PND. We have a subset of seven patients, for six we suspect sporadic de novo mutations, the seventh is a familial case.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-04-01T11:40:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000048","title":"Paroxysmal neurological disorders","description":"We are sequencing the exomes of patients with paroxysmal neurological disorders mainly focusing on migraine and epilepsy. Cases are collected from performance sites of members of the International Headache Genetics consortium and EuroEPINOMICS. Most cases have a strong family history. The study sample will include both cases and controls.","abstract":"We are sequencing the exomes of patients with paroxysmal neurological disorders mainly focusing on migraine and epilepsy. Cases are collected from performance sites of members of the International Headache Genetics consortium and EuroEPINOMICS. Most cases have a strong family history. The study sample will include both cases and controls.","study_type":"Other","pubmed_ids":[25262651],"external_links":null,"is_released":true,"released_date":"2011-04-01T14:28:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000049","title":"Exome_sequencing_in_patients_with_Calcific_Aortic_Valve_Stenosis","description":"The objective is to identify new genes involved in calcific aortic valve stenosis (CAVS) by screening the exome of at least 20 patients with familial CAVS. The recruitment of patients with CAVS has been achieved by l’institut du thorax (Nantes, France). DNA from the selected patients has been analysed by exome capture (Agilent SureSelect) and massively parallel sequencing (Illumina). The data generated by this project will lead to the identification of candidate genes involved in CAVS, which can be further screened for mutation in additional patients with CAVS.","abstract":"Calcific aortic valve stenosis (CAVS) is the most frequent heart valve disease, but despite its high incidence in the ageing population, pathophysiologic mechanisms are unknown and the only therapy is surgical valve replacement. The aim of this project is to screen the exome of patients with familial CAVS to identify new genes associated with the disease. These genes will be screened for further mutations in additional patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-04-04T16:53:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000050","title":"Investigating_low_frequency_variants_in_CAD_MI_cases__controls_and_pedigrees_using_whole_exome_sequencing_and_custom_pulldowns","description":"The Cardiogenics re-sequencing study will consist of three parts: Eight pools of 25 individuals will be sequenced using a Nimblegen hybrid-capture solution specific to miRNA sequences, 80 pools of 25 individuals will be sequenced using a custom Agilent SureSelect array covering genes associated with coronary artery disease (CAD) and myocardial infarction (MI), 10 individuals from families with a history of CAD/MI will be exome sequenced using the Sanger exome array. The experiment will use the early onset patients from the German MI cohort and the UK BHF CAD/MI cohort both of which have strong family history. For controls we will consider individuals from the UKBS and KORA cohorts.","abstract":"In rare cases, coronary artery disease (CAD) and myocardial infarction (MI) appear to be inherited in an autosomal-dominant mode. Cardiogenics has access to 19 multi-generation families (max. 27 MI patients per family) displaying an autosomal dominant inheritance pattern for severe CAD / MI using systematic large scale screening. Linkage analyses in these families have revealed so far a limited number of peacks and only in one instance two families with the same linkage peak on chromosome 8q. Resequencing of biological candidates in this large interval has not yield any mutations so far. We propose to sequnce the exome of 10 affected individuals one per family and include the two families with the 8q linakge. We anticipate genotyping interesting variants in all family members In Cardiogenics the recent meta-analyses of GWAS studies under the CARDIOGRAM umbrella has identified several new loci reaching genome wide significance with several more currently under replication. We anticipate that upon completion of the replication phase of CARDIOGRAM we will have close to 30 CAD/MI confirmed loci. We want to investigate the presence or absence of high penetrance, low frequency variants in these confirmed regions of association focusing initially on exonic sequences that are more likely to harbor. In addition, functional annotation of variants outside coding regions is not yet available. As CAD/MI is currently not scheduled within WTCCC+ Cardiogenics want to proceed with the experiment using the same design of resequencing up to 1000 cases and 1000 controls in pools of 25 individuals. The experiment will use the early onset patients from the German MI cohort and the UK BHF CAD/MI cohort both of which have strong family history and together total over 5000 cases. For controls we will consider individuals from the UKBS and KORA cohorts. We will use the recently installed Syzygy software for calling variants from these pools. Variants that are functionally important and show strong enrichment in the case vs control pools will be considered for follow up by genotyping in 8K + 8K cases/controls Micro RNA (miRNA) sequences have recently been found to have a profound impact on complex disease, however, so far, no study has investigated these sequences in association with CAD and MI. We have designed a solution hybrid capture array that is targeted to known miRNA sites, in order to find high penetrance rare variants in these regions. We will sequence 4 pools of case and and 4 pools of controls from the above-mentined UK and German collections.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-04-04T16:54:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000051","title":"Sequencing_of_RNA_samples_from_haematopoietic_cells","description":"As part of the Cardiogenics collaboration we have performed an e-QTL study in monocytes and macrophages in 425 health individuals of the Cambridge BioResource. To better define the transcript landscape of both cells we wish to sequence the RNA of monocytes, macrophages and other relevant haematopoietic cells/cell lines.","abstract":"As part of the Cardiogenics collaboration we have performed an e-QTL study in monocytes and macrophages in 425 health individuals of the Cambridge BioResource. To better define the transcript landscape of both cells we wish to sequence the RNA of monocytes, macrophages and other relevant haematopoietic cells/cell lines.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000052","title":"PAS Pedigrees: Identification of novel genetic variants contributing to cardiovascular disease in pedigrees with premature atherosclerosis.","description":"The heritability of CVD has been estimated to be between 40 and 55%. Due to the low MAF, PAS-causing mutations cannot be identified by indirect genotyping because their presence cannot be inferred from common haplotypes, as has been done successfully to uncover common risk variants by GWAS. It has been shown by Ng et al that the causative gene for rare syndromes can be unequivocally identified by sequencing the exomes of only four cases and eight controls. We expect exome sequencing to result in a high number of mutations and non-causitive coding variants.","abstract":"Early onset CVD or premature atherosclerosis (PAS) is associated with a greater heritability. Over the last two years pedigree histories have been compiled from the AMC-PAS cohort and so far ten families have been identified with evidence of autosomal inheritance of CVD without any known monogenic causes of CVD. We wish to test the hypothesis that in these pedigrees novel rare allelic variants or mutations might result in the clinical phenotypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-04-05T15:50:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000053","title":"Investigation of the genetic basis of the rare syndrome Post-Transfusion Purpura (PTP)","description":"The Post-Transfusion Pupura (PTP) syndrome although rare has severe side effects for 5-10 cases per annum in the UK as a result of transfusion. High quality DNA has been isolated from either whole blood or from cryopreserved mononuclear cells of 4 patients in order to study our postulation that the condition is caused by a loss-of-function mutation in a specific gene.","abstract":"The project studies the genetic basis of the rare syndrome PTP which in ~5-10 cases per annum in the UK can lead to severe side effects as a result of transfusion. We have 4 patient samples for this study.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-04-05T15:52:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000054","title":"Identifying causative mutations for Thrombocytopenia with Absent Radii","description":"Thrombocytopenia with Absent Radii is an inherited disorder that manifests itself with major limb skeletal abnormalities and low platelet count (and therefore a bleeding diathesis). The syndrome is well-characterised and defined phenotypically and there is a well-established database of UK-based families affected with ths disorder. The causative mutation for the disorder is yet to be identified. If known, it would allow for pre-natal screening and counselling avoiding life-long care for patients who are affected and are therefore severely disabled. We postulate that exon sequencing of 4 unrelated affected individuals would give enough power to narrow down potential candidate mutations which would thereafter be confirmed using DNA from other affected families.","abstract":"Exome sequencing of Bristol cohort with TAR disorder","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-04-05T15:53:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000055","title":"Analysis_of_genomic_integrity_of_disease_corrected_human_induced_pluripotent_stem_cells_by_exome_sequencing","description":"Induced pluripotent stem (iPS) cells hold great promise for autologous cell transplantation. In order to apply this therapy to monogenic disorder, disease-causing mutations must be corrected prior to transplantation. We generated iPS cells from patients with alpha-1 antitrypsin deficiency, which is caused by homozygous non-synonymous mutation in the SERPINA1 gene. In vitro differentiation of patient-derived iPS cells to hepatocytes showed recapitulation of the disease phenotype. We corrected the mutations by gene targeting using zinc finger nuclease (ZFN) and piggyBac transposon technologies. Our mutation correction is highly accurate. There is no exogenous sequence left behind at the targeted site. The corrected iPS cell-derived hepatocytes were indistinguishable from healthy hepatocyte, suggesting that the corrected gene was fully functional. The genomic integrity was also analyzed by CGH and SNP array, showing no genomic alterations. These are important points to ensure clinical safety as well as functional restoration of the corrected gene. One remaining question is if these corrected iPS cells are clinically safe at the single base-pair level. Recent publications suggested that cancer-related mutations are significantly accumulated during iPS cell propagation. We aim to assess the clinical safety of the corrected iPS cells by using exome sequencing. Outcome from this project would bring iPS cell technology one step closer to clinical applications.","abstract":"Induced pluripotent stem (iPS) cells hold great promise for autologous cell transplantation. In order to apply this therapy to monogenic disorder, disease-causing mutations must be corrected prior to transplantation. We generated iPS cells from patients with alpha-1 antitrypsin deficiency, which is caused by homozygous non-synonymous mutation in the SERPINA1 gene. In vitro differentiation of patient-derived iPS cells to hepatocytes showed recapitulation of the disease phenotype. We corrected the mutations by gene targeting using zinc finger nuclease (ZFN) and piggyBac transposon technologies. Our mutation correction is highly accurate. There is no exogenous sequence left behind at the targeted site. The corrected iPS cell-derived hepatocytes were indistinguishable from healthy hepatocyte, suggesting that the corrected gene was fully functional. The genomic integrity was also analyzed by CGH and SNP array, showing no genomic alterations. These are important points to ensure clinical safety as well as functional restoration of the corrected gene. One remaining question is if these corrected iPS cells are clinically safe at the single base-pair level. Recent publications suggested that cancer-related mutations are significantly accumulated during iPS cell propagation. We aim to assess the clinical safety of the corrected iPS cells by using exome sequencing. Outcome from this project would bring iPS cell technology one step closer to clinical applications.","study_type":"Other","pubmed_ids":[21993621],"external_links":null,"is_released":true,"released_date":"2011-04-05T16:27:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000056","title":"Discovery_of_the_genetic_basis_of_rare_syndromes_diseases_relevant_to_Cardiovascular_Diseases_","description":"As part of the Bloodomics collaboration we have collected four categories ([i] to [iv]) of pedigrees with diseases/syndromes relevant to cardiovascular diseases. A pilot exome sequencing study is proposed on a subset of 20 samples across the 4 categories.","abstract":"As part of the Bloodomics collaboration we have collected four categories ([i] to [iv]) of pedigrees with diseases/syndromes relevant to cardiovascular diseases. It is proposed to enter 20 propositus cases (5/category) in the Exome Seq pipeline and to perform a scan for rare CNVs. All 4 clinical categories are examples of extreme rare diseases. It is postulated that disease in the four categories of cases is caused by a spectrum of unique sequence variants in as yet non-defined loci. It can be reasoned that the genetic events underlying disease will be of coding nature or a rare copy number variant in a number of cases. In all pedigrees of categories (i), (ii) and (iv) the normal genetic causes have been excluded. Cases from a French network (iii) will be tested for sequence events known to be associated with platelet function disorders before entry in the Exome Seq pipeline. Our aim is to define the genetic basis of the rare syndromes relevant to cardiovascular diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000057","title":"An exome sequencing pilot study of HIV elite-long term non progressors and rapid progressors","description":"A pilot study examining genetic determinants associated with elite long term non progression and rapid progression using exome sequencing of individuals at the extremes of the distribution of HIV control and progression. Data can only be used for HIV related research.","abstract":"A rare subgroup of HIV infected individuals naturally controls infection without treatment. These ‘elite controllers’ constitute an important model for the natural control of HIV infection. Indeed, the study of these individuals may provide insights into strategies for the development of HIV vaccines. Although several HLA and chemokine alleles are known to be over-represented in elite controllers, only a small portion of HIV phenotypic variation is explained by known genetic variants. The elite controller phenotype is rare and distinct, representing the extreme of an infectious disease trait. As such, this phenotype may be partly explained by variation in host immune control, which may be characterized by differences in rare functional genetic variants. Genomic regions underlying elite control can be potentially identified by comparing the presence or frequency of variants in this group to that representing the opposite extreme. In this context, ‘rapid progressors’ is a group defined by its rapid immunological and clinical disease progression. This pilot study aims to identify DNA sequence variants involved in the control of HIV infection and rapid progression in genetically diverse populations. Specifically, we aim to sequence the exomes of 15 elite controllers and 15 rapid progressors from multiple ethnic groups from Europe, sub-Saharan Africa and China.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-04-12T09:27:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000058","title":"Acute_Lymphoblastic_Leukemia_Sequencing","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 50 Acute Lymphoblastic Leukemia samples and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 100 exome libraries and mapped build 37 of the human reference genome to facilitate the identification of novel cancer genes. In addition, 500bp, NO_PCR total genomic libraries will be prepared from the same samples and five lanes of Illumina GA sequencing will be analysed to characterise genome wide, somatically acquired structural variation.","abstract":"Cancer is driven by mutation. Illumina GA massively parallel sequencing technology will be applied to Agilent exome hybridisation capture libraries and total genomic paired-end libraries from 50 matched human Acute Lymphoblastic Leukemia samples. Bespoke algorithms are being developed to identify the somatically acquired structural variants, point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with Acute Lymphoblastic Leukemia development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-04-13T17:33:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000059","title":"De_novo_mutations_in_schizophrenia_","description":"Project contains full exome data from 100-150 trios (up to 450 samples)","abstract":"Recent work has suggested that de novo mutations contribute to the susceptibility of some neurodevelopmental disorders, e.g. mental retardation.  This has stimulated the hypothesis that de novo mutations could also be involved in severe psychiatric traits, such as schizophrenia.  Within the UK10K project there is a strong aim to identify coding variants associated to schizophrenia, but the study design does not include de novo mutation identification.  The aim in this project is to sequence the exome of parent offspring trios, where the child suffers from schizophrenia, but parents do not have the diagnosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-04-14T13:51:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000060","title":"Whole_genome_sequencing_in_a_multiplex_Crohn_s_disease_family","description":"In 2009 we identified a four-generation family with over 700 members and 41 affected with Crohn's disease (CD).  At the time we sequenced the exome of 6 affected individuals but did not identify any coding variants which appear to explain the high prevalence of disease.  Since then we have collected DNA from a large number of additional family members, genotyped linkage arrays on the entire family to refine genomic regions shared by identity by descent and genotyped affected and unaffected members at known CD risk loci identified by Genome Wide Association Studies (GWAS).  These analyses have confirmed that a significant unexplained excess of disease remains after accounting for all known genetic factors, and that several regions of the genome are shared by a large fraction of affected individuals.  We therefore perform whole genomes sequencing from 8 individuals which will allow us to impute the complete sequence of nearly all the members of the two largest and most severely affected branches of the family.","abstract":"In 2009 we identified a four-generation family with over 700 members and 41 affected with Crohn's disease (CD).  At the time we sequenced the exome of 6 affected individuals but did not identify any coding variants which appear to explain the high prevalence of disease.  Since then we have collected DNA from a large number of additional family members, genotyped linkage arrays on the entire family to refine genomic regions shared by identity by descent and genotyped affected and unaffected members at known CD risk loci identified by Genome Wide Association Studies (GWAS).  These analyses have confirmed that a significant unexplained excess of disease remains after accounting for all known genetic factors, and that several regions of the genome are shared by a large fraction of affected individuals.  We therefore perform whole genomes sequencing from 8 individuals which will allow us to impute the complete sequence of nearly all the members of the two largest and most severely affected branches of the family.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-04-21T17:04:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000061","title":"Lethal malformation syndrome","description":"Identification of the genetic basis of rare monogenic diseases can provide insights into disease mechanisms, biological pathways and potential therapeutic targets. Exome sequencing has proven to be a powerful, efficient strategy for the identification of the genes underlying rare Mendelian disorders. The genetic defect behind the lethal malformation syndrome under study is known in some cases and has proven useful in revealing the primary underlying defect. We have six typical unrelated families with no known mutation.  The aim of this study is to identify the locus associated with this lethal malformation syndrome in these families using exome sequencing.","abstract":"The genetic defect behind the lethal malformation syndrome under study is known in some cases and has proven useful in revealing the primary underlying defect. We have six typical unrelated families with no known mutation.  The aim of this study is to identify the locus associated with this lethal malformation syndrome in these families using exome sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-05-04T13:39:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000062","title":"The_International_1q_type_2_diabetes_consortium","description":"The aim of this project is to identify rare variants in the 1q region associated with type 2 diabetes. To this end 651 case samples and 651 control samples from six populations have been pooled (pool sizes range from 27-33 individuals), and are being sequenced. The hybridization solution being used captures the exons and UTRs of genes in the 1q region.","abstract":"Linkage studies have consistently shown a type 2 diabetes association in the chromosome 1q21-25 region (Prokopenko et al. 2009). However, as yet the causal variant has not been identified. The fact that high-throughput genome wide association studies have failed to positively identify T2D associated variants in this region suggest that the association is due to low frequency, high to moderate penetrance variants. The project aims to identify type 2 diabetes susceptibility genes through a systematic, comprehensive analysis of a ~25Mb region of chromosome 1q21-25 which harbours an extremely well replicated type 2 diabetes linkage signal, seen in over 10 genome scans. Exhaustive analysis of common variants through targeted and whole genome SNP typing in multiple ethnic groups hasn't yield any significant association with T2D. To investigate whether lower frequency variants are underlying the observed T2D linkage signal we have undertaken a systematic resequencing of  exons across the ~340 genes in the region using ~1000 T2D cases and 1000 controls. Individuals have been selected from several populations available to the consortium (UK, French, Chinese, African Americans, Pima Indians, Amish) and organised in 60 pools of ~33 samples each; an equal number of case and control pools has been prepared from each ethnic group. In the first phase of the experiment we designed a Nimblegen array covering ~500kb of exons and other regulatory regions of the 65 most biologically significant genes and sequencing is in progress. We propose to complete this experiment by resequencing coding exons in the remaining 276 genes using the SureSelect platform for the pulldown step targeting ~1Mb of exonic sequences.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-05-06T11:17:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000063","title":"Exome_sequencing_in_patients_with_cardiac_arrhythmias","description":"The institut du thorax in Nantes (FR), the Academic Medical Center in Amsterdam (NL) and the University Hospital of Muenster (DE) have recruited 20 large families comprising at least 3 patients with cardiac arrhythmias and showing history of sudden cardiac death. For each family, the exome of one affected individual has been sequenced at the Wellcome Trust Sanger Institute (UK), in order to identify new genes associated with high risk of sudden cardiac death.","abstract":"Sudden cardiac death (SCD) is defined as an unexpected, non-traumatic death occurring within one hour after symptom onset. It claims almost one million deaths annually in the USA and Europe and results most frequently from ventricular fibrillation. DNA from patients with cardiac arrhythmias has been analysed by whole-genome exon capture and massively parallel sequencing. The data generated by this project will lead to the identification of new candidate genes involved in sudden cardiac death, which can be further tested for mutation in additional patients to estimate their relative contributions to cardiac arrhythmias.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-05-06T13:43:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000064","title":"Genetics of Microcephalic Osteodysplatics Primordial Dwarfism","description":"This project aims to find causal variants in 50 patients diagnosed with Microcephalic Osteodysplastic Primordial Dwarfism (MOPD), of presumed recessive inheritance performing whole exome sequencing to ~50x mean depth. This is a collaboration with Prof A. Jackson, MRC Human Genetics Unit, Edinburgh","abstract":"This project aims to find causal variants in 50 patients diagnosed with Microcephalic Osteodysplastic Primordial Dwarfism (MOPD), of presumed recessive inheritance performing whole exome sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-05-13T09:23:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000065","title":"Whole_genome_sequencing_of_Crohn_s_disease_patients","description":"Population based sequencing of whole genomes of Crohn's disease patients.","abstract":"We propose to begin sequencing whole genomes from population CD samples in mid 2011, to be ramped up in the first year of the QQ. The aim is to identiy low frequency and rare variation which contributes to CD risk but is not easily detectable by GWAS. Thes sequences will be compared to UK10K and Cambridge BioResource controls.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-05-17T16:04:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000066","title":"Congenital Heart Disease in UK Families","description":"This project aims to identify highly penetrant coding variants increasing the risk of Congenital Heart Disease (CHD) performing whole exome sequencing on DNA samples from 23 affected individuals, selected from 10 families with presumed Autosomal Recessive Inheritance. This is a collaboration with Prof. Eamonn Maher and Dr. Chirag Patel from the Department of Medical and Molecular Genetics, University of Birmingham plans to sequence 23 indexed Agilent whole exome pulldown libraries on 75Bp PE HiSeq (Illumina).","abstract":"This project aims to identify highly penetrant coding variants increasing the risk of Congenital Heart Disease (CHD) performing whole exome sequencing on DNA samples from 23 affected individuals, selected from 10 UK families with presumed Autosomal Recessive Inheritance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-05-18T09:19:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000067","title":"Samples from the Greek island of Crete, MANOLIS cohort","description":"Genome-wide association studies of complex traits have been successful in identifying common variant associations, but a substantial heritability gap remains. The field of complex trait genetics is shifting towards the study of low frequency and rare variants, which are hypothesised to have larger effects. The study of these variants can be empowered by focusing on isolated populations, in which rare variants may have increased in frequency and linkage disequilibrium tends to be extended. This work focuses on isolated populations from Greece. Sequencing is very efficient in isolated populations, because variants found in a few samples will be shared by others in extended haplotype contexts, supporting accurate imputation.","abstract":"Genome-wide association studies of complex traits have been successful in identifying common variant associations, but a substantial heritability gap remains. The field of complex trait genetics is shifting towards the study of low frequency and rare variants, which are hypothesised to have larger effects. The study of these variants can be empowered by focusing on isolated populations, in which rare variants may have increased in frequency and linkage disequilibrium tends to be extended. This work focuses on isolated populations from Greece. Sequencing is very efficient in isolated populations, because variants found in a few samples will be shared by others in extended haplotype contexts, supporting accurate imputation.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-05-19T15:54:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000068","title":"ORCADES_WGA","description":"The ORCADES Whole Genome Sequence Study plans to sequence the genomes of 400 subjects from the Orkney Complex Disease Study (ORCADES) at low coverage, each with data on up to 300 quantitative traits and other risk factors associated with cardiovascular, metabolic and other complex diseases","abstract":"The ORCADES Whole Genome Sequence Study will whole genome sequence at low coverage 400 subjects from the Orkney Complex Disease Study (ORCADES), each with data on up to 300 quantitative traits and other risk factors associated with cardiovascular, metabolic and other complex diseases, thus providing further value for money. Traits include novel plasma N-glycan intermediate phenotypes, known to be important in many disease processes, whole body DEXA scans and five domains of cognition, in addition to the more commonly measured risk factors. Because of high levels of kinship in the population, by resequencing the genomes of a subset of participants, it is possible to accurately impute the genomes of the entire sample using long-range phasing (LRP) based on the Illumina genome scan data. Association and linkage of rare and common variants with study traits will be analysed in a total ORCADES sample of ~2100; results will also contribute to meta-analyses. Locus-wide signals and/or individual variants will be replicated in large (n&gt;20,000) Scottish resources available to us, using genotyping or sequencing as necessary. The effect of including rare variants on the efficacy of individual disease risk prediction algorithms will be assessed in prospective cohorts.  The sequence data will also be used to analyse population structure and as a model for sequencing studies on genetically enriched isolates.  This study has a biobank of DNA, whole blood, plasma and serum stored, thus the whole genome sequences will consolidate a rich platform resource for future research. The Scottish Health Service Information and Statistics Division has performed record linkage for all consenting study participants thus we have access to cancer registrations and hospital admissions since 1981 with prospective flagging for admissions and deaths going forward.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-05-23T12:11:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000069","title":"Determination of the molecular nature of the Vel blood group by exome sequencing","description":"The genetic basis of the Vel group is yet to be determined. We have collected DNA samples from about 90 Vel negative blood donors by phenotyping 270,000 donors. Understanding the genetic basis of the Vel group could have clinical significance as transfusion of Vel positive blood to Vel negative recipients with anti-Vel can cause severe and acute haemolytic transfusion reactions.","abstract":"The project studies the genetic basis of the Vel blood group which could have clinicial significance as transfusion of Vel positive blood to recipients with anti Vel can cause severe and acute haemolytic transfusion reactions. We have sequenced 4 patient samples for this study.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-05-27T15:11:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000070","title":"Recurrent Somatic Mutations in CLL","description":"The Chronic Lymphocytic Leukemia (CLL) Genome Project aims to identify genetic alterations involved in the development and progression of the CLL, which are still unknown, with the objective of generating a comprehensive catalogue of genetic alterations in 500 independent tumours.    \n               The CLL Genome Project, as a contributing member of the International Cancer Genome Consortium (ICGC), has the purposes of creating diagnostic tools, discovering therapeutic targets and developing new strategies that will allow a customized therapy for CLL in order to make it more precise and effective.","abstract":"The Chronic Lymphocytic Leukemia (CLL) Genome Project aims to identify genetic alterations involved in the development and progression of the CLL, which are still unknown, with the objective of generating a comprehensive catalogue of genetic alterations in 500 independent tumours.                   The CLL Genome Project, as a contributing member of the International Cancer Genome Consortium (ICGC), has the purposes of creating diagnostic tools, discovering therapeutic targets and developing new strategies that will allow a customized therapy for CLL in order to make it more precise and effective.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000071","title":"Tetralogy of Fallot Exome Trios","description":"Exome sequencing of 30 parent-offspring trios to &gt;50X mean depth, where the offspring has sporadic TOF, to identify potential causal de novo mutations. We will use the exome plus design for pulldown that incorporates ~6.8Mb of additional regulatory sequences in addition to the ~50Mb GENCODE exome.","abstract":"Tetralogy of Fallot (TOF) is one of the most recognisable congenital heart defects, comprising four distinct anatomical anomalies: pulmonary stenosis, ventral septal defect, over-riding aorta and right ventricular hypertrophy. TOF occurs in 1/3000 live births and accounts for about 10% of all serious congenital heart disease. About 20% of TOF is caused by cytogenetically visible chromosomal abnormalities (i.e. Trisomy chr21). A recent study has shown that the prevalence of de novo CNVs in sporadic patients with TOF is about 10%, which is 5-10x higher than in controls (Greenway et al 2009 Nature Genetics). Mutations in 7 genes (GATA4, TBX1, TBX5, NKX2-5, NOTCH1, NOTCH2 and JAG1) have been shown to cause TOF, although these explain only a small fraction of TOF cases, and mutations in these genes more typically cause other types of congenital heart defect. About 70% of sporadic cases of TOF remain unexplained at the genetic level. We perform exome sequencing on 30 parent-offspring trios to &gt;50X mean depth, where the offspring has sporadic TOF, to identify potential causal de novo mutations using software developed in the Hurles group for the de novo mutation analyses in the 1000 genomes project. We use the ExomePlus design for target preparation that incorporates ~6.8Mb of additional regulatory sequences in addition to the ~50Mb GENCODE exome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-06-08T08:22:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000072","title":"Extreme_phenotypes__Exome_sequencing_of_individuals_hospitalised_with_severe_influenza_infection_during_the_MOSAIC_and_GenISIS_studies","description":"Host genetics are important in severe infection phenotypes such as death or hospitalisation. In effect, extreme infection phenotypes can be considered similar to extreme drug reactions in that the majority of the population exhibits a 'typical' response, but a small subset can have an extreme response. In infection this extreme response can be either adverse pathology, outside the normal range or intrinsic resistant to infection. Whilst the later can be conferred by immune memory, in the case of new infections where pre-existing immunity does not exist then these 'resistant' individuals may have an underlying genetic protection. The intrinsically resistant and severe infection groups represent the extreme phenotypes of the infection spectrum. By combining a very high attack rate, a rare severe illness phenotype and an unchanged pathogen when comparing severe to community (uncomplicated) infection, the 2009-11 influenza outbreaks created an almost perfect situation for identifying genetic susceptibility markers to an emerging disease. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"From ~200 individuals hospitalised for severe influenza we have identified 40, ethnically matched people with no underlying co-morbidities for whole exome sequencing, including a mother-child pair. The whole exome data will be compared with existing exome data at the WTSI as the general population acts as an initial control group. This study will aim to identify host genetic components of severe influenza infection.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000073","title":"The_role_of_CpG_island_methylation_in_immune_cell_gene_regulation","description":"Tissue-specific methylation patterns suggest a role for CpG island methylation in differentiation and cell-type-specific gene regulation. We have profiled CpG island methylation in different cells of the immune cell lineage to investigate this role. MBD-affinity purification combined with next generation sequencing was used to analyse CpG island methylation in dendritic cells, B cells, Th1, Th2 and naïve T cells. ChIP-seq was carried out to determine RNA polymerase II binding sites in these cell types and this was compared to the methylation profiles obtained. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We have profiled CpG island methylation in various immune system cell types and related this to gene expression in these cells.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000074","title":"Screening_for_human_epigenetic_variation_at_CpG_islands","description":"Many human characteristics, including susceptibility to disease, are determined genetically. An unexplored alternative to such genetic determination concerns epigenetic mechanisms such as DNA methylation. CpG islands (CGIs) are generally constitutively hypomethylated, however there are circumstances in which they become heavily methylated and, when coincident with a gene promoter, this invariably causes transcriptional silencing. CGI methylation occurs in normal tissues during processes such as X-inactivation, but abnormal patterns of methylation have also been implicated in disease. The vast majority of evidence relates to cancer, where silencing of multiple genes in this way appears to be a causal contributor to the cancer state. To address the role and extent of CGI methylation in ‘normal’ and diseased cells we applied MBD-affinity purification in conjunction with next generation sequencing in a panel of human brain autopsy samples. These samples represent a panel of individuals as well as specific brain regions and neurological pathologies.","abstract":"This projects aims to dissect the contribution of aging, tissue specificity and neurological pathology on CGI methylation in primary human brain biopsy samples","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-06-17T10:39:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000075","title":"Functional_characterisation_of_CpG_islands_in_human_and_mouse_tissues","description":"Tissue-specific methylation patterns suggest a role for CpG island (CGI) methylation in differentiation and cell-type-specific gene regulation. We have applied CXXC affinity purification (CAP), MBD affinity purification (MAP) and chromatin immunoprecipitation (ChIP) in combination with solexa sequencing to investigate the extent and functional significance of CGI methylation in sperm, blood, cerebellum and ES cells for both human and mouse.","abstract":"This project aims to determine the relationship between the physical properties and distribution of CGIs and relate this to DNA methylation, chromatin state and transcriptional competence.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-06-17T15:58:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000076","title":"Screening_for_abnormal_CGI_methylation_in_primary_colorectal_tumours","description":"A common hallmark of neoplastic cells is abnormal acquisition of CpG island (CGI) methylation and the silencing of associated gene promoters. To determine the extent and distribution of CGI methylation in colorectal cancer, we solexa sequenced MBD affinity purified DNA prepared from five colorectal tumours and matched colon mucosa from the same individuals.","abstract":"This project aims to identify, quantify and characterise sites of abnormal CGI methylation in primary colorectal cancer samples.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-06-17T16:00:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000077","title":"Human_Colorectal_Cancer_Exome_Sequencing","description":"In this experiment we sequenced a collection of genes identified as being mutated in a Sleeping Beauty Screen in a mouse colorectal Cancer Model in human tumours collected from patients with germline mutations in APC and also other familial CRC predisposition syndromes. We also sequenced the germline of these patients allowing us to identify somatically mutated genes. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"In this experiment we sequenced a collection of genes identified as being mutated in a Sleeping Beauty Screen in a mouse colorectal Cancer Model in human tumours collected from patients with germline mutations in APC and also other familial CRC predisposition syndromes. We also sequenced the germline of these patients allowing us to identify somatically mutated genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-06-23T08:16:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000078","title":"SFHS_pedigrees","description":"Deep (&gt;25x mean coverage) whole genome sequencing on 5-10 families drawn from the Scottish Family Health Study with four or more children.","abstract":"Rates of germline mutation are thought to depend on age and sex. This project aims to estimate the effect of age and sex on mutation rates by identifying new (de novo) mutations in children that are not found in either parent, ascribing these mutations to the paternal or maternal germline by haplotyping the new allele with nearby inherited alleles, and investigating whether the numbers of paternal or maternal germline mutations changes with increasing parental age. By studying families in which parents have had multiple children over a long period of time, we can control for potential genetic or environmental influences on mutation rate and maximise our power to detect the influence of age on mutation rate. In this study, we are performing deep (&gt;25X mean coverage) whole genome sequencing on 5-10 families drawn from the Scottish Family Health Study with four or more children.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-06-23T14:54:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000079","title":"Cardiogenics_re_sequencing","description":"The Cardiogenics re-sequencing study will consist of three parts: Eight pools of 25 individuals will be sequenced using a Nimblegen hybrid-capture solution specific to miRNA sequences, 80 pools of 25 individuals will be sequenced using a custom Agilent SureSelect array covering genes associated with coronary artery disease (CAD) and myocardial infarction (MI), 10 individuals from families with a history of CAD/MI will be exome sequenced using the Sanger exome array. The experiment will use the early onset patients from the German MI cohort and the UK BHF CAD/MI cohort both of which have strong family history. For controls we will consider individuals from the UKBS and KORA cohorts.","abstract":"In rare cases, coronary artery disease (CAD) and myocardial infarction (MI) appear to be inherited in an autosomal-dominant mode. Cardiogenics has access to 19 multi-generation families (max. 27 MI patients per family) displaying an autosomal dominant inheritance pattern for  severe CAD / MI using systematic large scale screening.  Linkage analyses in these families have revealed so far a limited number of peacks and only in one instance  two families with the same linkage peak  on chromosome 8q. Resequencing of biological candidates in this large interval has not yield any mutations so far. We propose to sequnce the exome of 10 affected individuals one per family and include the two families with the 8q linakge. We anticipate genotyping interesting variants in all family membersIn Cardiogenics the recent meta-analyses of GWAS studies under the CARDIOGRAM umbrella has identified several new loci reaching genome wide significance with several more currently under replication. We anticipate that upon completion of the replication phase of CARDIOGRAM we will have close to 30 CAD/MI confirmed loci. We want to investigate the presence or absence of high penetrance, low frequency variants in these confirmed regions of association focusing initially on exonic sequences that are more likely to harbor. In addition, functional annotation of variants outside coding regions is not yet available. As CAD/MI is currently not scheduled within WTCCC+ Cardiogenics want to proceed with the experiment using the same design of resequencing up to 1000 cases and 1000 controls in pools of 25 individuals. The experiment will use the early onset patients from the German MI cohort and the UK BHF CAD/MI cohort both of which have strong family history and together total over 5000 cases. For controls we will consider individuals from the UKBS and KORA cohorts. We will use the recently installed Syzygy software for calling variants from these pools. Variants that are functionally important and show strong enrichment in the case vs control pools will be considered for follow up by genotyping  in 8K + 8K cases/controlsMicro RNA (miRNA) sequences have recently been found to have a profound impact on complex disease, however, so far, no study has investigated these sequences in association with CAD and MI. We have designed a solution hybrid capture array that is targeted to known miRNA sites, in order to find high penetrance rare variants in these regions. We will sequence 4 pools of case and and 4 pools of controls from the above-mentined UK and German collections.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-06-24T11:18:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000080","title":"CRLF2_sequencing_project_","description":"I hope to gain insight into novel genetic aberrations present in these patients that will highlightimportant pathways that are involved in this subtype of leukaemia. It would be interesting to see ifthe mutations and pathways that are activated are consistent between the patients, or differencesare observed dependent upon whether the patient has the translocation or the PAR1 deletion. Ofnote is the high association with either numerical gains of chromosome X or numerical/structuralabnormalities of chromosome 21 (Down syndrome, iAMP21) in patients with CRLF2 deregulation. Ihope to find abnormalities linking chromosomes X and 21 to CRLF2 deregulation in BCP‐ALL. Byincluding the three patients that are normal for CRLF2, but have consistent genetic abnormalitiesfound in the experimental cohort, I expect to find genetic differences between these two groupsthat will help us to identify novel molecular targets specific to CRLF2 deregulation.","abstract":"We have recently reported the novel involvement of cytokine receptors with the immunoglobulinheavy chain locus (IGH@) in B‐cell precursor acute lymphoblastic leukaemia (BCP‐ALL)1,2. Wediscovered two novel, cryptic chromosomal abnormalities: a translocation, either t(X;14)(p22;q32) ort(Y;14)(p11;q32) and an interstitial deletion, either del(X)(p22.33p22.33) or del(Y)(p11.32p11.32),involving the pseudoautosomal region (PAR1) of the sex chromosomes. This resulted in deregulatedexpression of, cytokine receptor‐like factor 2, CRLF2, due to juxtaposition to the IGH@ enhancer orthe promoter of the purinergic gene, P2RY8, respectively. This was associated with activation of theJAK‐STAT pathway in cell lines, patients and transduced primary B‐cell progenitors, sustaining theirproliferation and indicating a causal role of CRLF2 deregulation in lymphoid transformation. We alsoidentified deletions of the cell cycle control gene, CDKN2A and B‐cell differentiation genes PAX5 andIKZF1 by a combination of FISH and aCGH studies as well as mutations of JAK1 and JAK2 by DHPLC. Itappears that overexpression of CRLF2 alone is insufficient to initiate leukaemogenesis. Howeverpatients have different combinations of the co‐operating abnormalities mentioned above, whichsuggests the presence of other as yet identified abnormalities that may be initiatingleukaemogenesis in this subtype of ALL. CRLF2 deregulation appears to define a distinct patientsubgroup, affecting 5% of children with ALL, with a low incidence of visible primary geneticabnormalities and high risk of organ involvement. It is also the most prevalent acquired abnormalityin Down syndrome‐ALL (DS) (52%) where it appears to be associated with an inferior outcome(unpublished data). Since we identified this subgroup of patients, interest on CRLF2 has dramaticallyincreased with detailed investigations at the clinical and biological3‐7.In summary, we know that CRLF2 deregulation alone is insufficient to initiate transformation toleukaemia; however the identification of other genetic aberrations in this patient subgroup suggestsoncogenic cooperation of multiple targets and pathways. Although JAK2 mutations are present inCRLF2 deregulated patients, not all have this mutation while some acquire this mutation at relapse.The same is true for the other gene deletions mentioned above. Through analysis of the currentsmall number of patients, CRLF2 deregulation does not appear to significantly affect the survival ofthese patients. However, it is a potential molecular target that may provide a specific treatmentreducing the toxicity experienced with current generic protocols. This is particularly important in theDS‐ALL patients who tend to have a worse outcome not due to disease progression but treatmenttoxicity. Studying these patients in more detail, both genetically and functionally, will allow us tounravel these co‐operating events and decipher the relevant combination of genetic hits that arerequired for the development of this subtype of leukaemia. Such an approach will assist theidentification of those aberrations that are most appropriate targets for therapy.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-06-24T15:45:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000081","title":"CRLF2_sequencing_project_Exomes","description":"I hope to gain insight into novel genetic aberrations present in these patients that will highlight important pathways that are involved in this subtype of leukaemia. It would be interesting to see if the mutations and pathways that are activated are consistent between the patients, or differences are observed dependent upon whether the patient has the translocation or the PAR1 deletion. Of note is the high association with either numerical gains of chromosome X or numerical/structural abnormalities of chromosome 21 (Down syndrome, iAMP21) in patients with CRLF2 deregulation. I hope to find abnormalities linking chromosomes X and 21 to CRLF2 deregulation in BCP‐ALL. By including the three patients that are normal for CRLF2, but have consistent genetic abnormalities found in the experimental cohort, I expect to find genetic differences between these two groups that will help us to identify novel molecular targets specific to CRLF2 deregulation.","abstract":"We have recently reported the novel involvement of cytokine receptors with the immunoglobulin heavy chain locus (IGH@) in B‐cell precursor acute lymphoblastic leukaemia (BCP‐ALL)1,2. We discovered two novel, cryptic chromosomal abnormalities: a translocation, either t(X;14)(p22;q32) or t(Y;14)(p11;q32) and an interstitial deletion, either del(X)(p22.33p22.33) or del(Y)(p11.32p11.32), involving the pseudoautosomal region (PAR1) of the sex chromosomes. This resulted in deregulated expression of, cytokine receptor‐like factor 2, CRLF2, due to juxtaposition to the IGH@ enhancer or the promoter of the purinergic gene, P2RY8, respectively. This was associated with activation of the JAK‐STAT pathway in cell lines, patients and transduced primary B‐cell progenitors, sustaining their proliferation and indicating a causal role of CRLF2 deregulation in lymphoid transformation. We also identified deletions of the cell cycle control gene, CDKN2A and B‐cell differentiation genes PAX5 and IKZF1 by a combination of FISH and aCGH studies as well as mutations of JAK1 and JAK2 by DHPLC. It appears that overexpression of CRLF2 alone is insufficient to initiate leukaemogenesis. However patients have different combinations of the co‐operating abnormalities mentioned above, which suggests the presence of other as yet identified abnormalities that may be initiating leukaemogenesis in this subtype of ALL. CRLF2 deregulation appears to define a distinct patient subgroup, affecting 5% of children with ALL, with a low incidence of visible primary genetic abnormalities and high risk of organ involvement. It is also the most prevalent acquired abnormality in Down syndrome‐ALL (DS) (52%) where it appears to be associated with an inferior outcome (unpublished data). Since we identified this subgroup of patients, interest on CRLF2 has dramatically increased with detailed investigations at the clinical and biological3‐7. In summary, we know that CRLF2 deregulation alone is insufficient to initiate transformation to leukaemia; however the identification of other genetic aberrations in this patient subgroup suggests oncogenic cooperation of multiple targets and pathways. Although JAK2 mutations are present in CRLF2 deregulated patients, not all have this mutation while some acquire this mutation at relapse. The same is true for the other gene deletions mentioned above. Through analysis of the current small number of patients, CRLF2 deregulation does not appear to significantly affect the survival of these patients. However, it is a potential molecular target that may provide a specific treatment reducing the toxicity experienced with current generic protocols. This is particularly important in the DS‐ALL patients who tend to have a worse outcome not due to disease progression but treatment toxicity. Studying these patients in more detail, both genetically and functionally, will allow us to unravel these co‐operating events and decipher the relevant combination of genetic hits that are required for the development of this subtype of leukaemia. Such an approach will assist the identification of those aberrations that are most appropriate targets for therapy.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-06-24T15:46:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000082","title":"ALK_inhibitors_in_the_context_of_ALK_dependent_cancer_cell_lines","description":"Anaplastic lymphoma kinase (ALK) has recently been found to be a critical cancer gene in cases of lung cancer, neuroblastomas and lymphomas. ALK inhibitors  have  recently shown significant activity in lung cancer patients with tumours that harbour the EML4-ALK gene rearrangement, but already drug-resistance is emerging. We have taken a lung cancer cell line H3122 (with the EML4-ALK rearrangement) and generated clones resistant to a small molecule inhibitor of ALK by serial exposure to the drug over 8 weeks. We now wish to characterise at the exome level whether the acquisiton of resistance has been accompanied by the development of new mutations that we can take forward for further study as the potential mechansims underlying the resistance. We therefore propose to exome sequence the parental NCI-H3122 cell line as well as drug-resistant clones.","abstract":"Modeling resistance to anaplastic lymphoma kinase (ALK) inhibitors in the context of ALK-dependent cancer cell lines and exploring novel therapeutic strategies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-06-24T15:46:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000083","title":"CAGEKID: Cancer Genomics of the Kidney","description":"The aim of CAGEKID is to carry out comprehensive detection of DNA markers for conventional (clear cell) renal carcinoma. The project includes complete analysis of somatic and constitutional DNA variation, methylation patterns and expression in a large number of constitutional/tumor pairs. CAGEKID is a part of the International Cancer Genome Consortium, ICGC.","abstract":"The aim of CAGEKID is to carry out comprehensive detection of DNA markers for conventional (clear cell) renal carcinoma. The project includes complete analysis of somatic and constitutional DNA variation, methylation patterns and expression in a large number of constitutional/tumor pairs. CAGEKID is a part of the International Cancer Genome Consortium, ICGC.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-06-24T22:43:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000085","title":"Linking genes, genomic instability and molecular subgroups in medulloblastoma","description":"Brain tumors are the second most common pediatric cancer and carry the highest mortality rates in this age group. Medulloblastoma is the most frequent malignant brain tumor of childhood. Recent studies indicate that medulloblastoma comprises at least four sub-entities (SHH-signaling, WNT-signaling, Group-C, Group-D) that differ in molecular alterations, cell of origin, clinicopathological features and outcome. Further characterization of the entire spectrum of genomic alterations underlying the formation of these distinct groups is urgently needed to identify diagnostic and prognostic biomarkers for clinical management and uncover novel therapeutic targets.","abstract":"Brain tumors are the second most common pediatric cancer and carry the highest mortality rates in this age group. Medulloblastoma is the most frequent malignant brain tumor of childhood. Recent studies indicate that medulloblastoma comprises at least four sub-entities (SHH-signaling, WNT-signaling, Group-C, Group-D) that differ in molecular alterations, cell of origin, clinicopathological features and outcome. Further characterization of the entire spectrum of genomic alterations underlying the formation of these distinct groups is urgently needed to identify diagnostic and prognostic biomarkers for clinical management and uncover novel therapeutic targets.","study_type":"Whole Genome Sequencing","pubmed_ids":[22265402],"external_links":null,"is_released":true,"released_date":"2011-06-30T14:30:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000086","title":"Dilgom_Exome","description":"The Finrisk sample sets are part of the National FINRISK Study. It is a large population survey on risk factors of chronic, noncommunicable diseases. The survey is carried out since 1972 every five years using independent, random and representative population samples from different parts of Finland. The main results from the previous FINRISK 2007 survey are published.The National FINRISK Study Survey was carried out in 5 areas in Finland and 2000 inhabitants aged 25-75 years were invited to participate in each year. Among findings were that Finns continue to gain weight.Data from FINRISK surveys are used for many different research projects and for national health monitoring needs. The recent research activities deal, in addition to cardiovascular diseases and the classical risk factors, also with e.g. asthma and allergy, alcohol, socioeconomic factors and genetic epidemiology.The FINRISK study is part of the MORGAM Project (MONICA Risk, Genetics, Archiving and Monigraph), sponsored by the EU and MDECODE (Molecular Diversity and Epidemiology of Common Disease) program coordinated by the University of Michigan.The exome sequencing study will be part of the Dilgom study, which is a part of the larger Finrisk population based health study performed in Finland. It consists of 5000 individuals with a prospective aspect of metabolic traits. The cohort has been extensively phenotyped for their cardiovascular and metabolic status. So far, we have performed a 660K Illumina GWAS and a full genome wide expression study from peripheral blood cells of 500 individuals. The cohort has also been in total genotyped by the cardiometabochip","abstract":"The exome sequencing will be part of the Dilgom study, which is a part of the larger Finrisk population based health study performed in Finland. It consists of 5000 individuals with a prospective aspect of metabolic traits. The cohort has been extensively phenotyped for their cardiovascular and metabolic status. So far, we have performed a 660K Illumina GWAS and a full genome wide expression study from peripheral blood cells of 500 individuals. The cohort has also been in total genotyped by the cardiometabochip","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-06-30T15:13:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000087","title":"Burden_of_Disease_in_Sarcoma","description":"Genomic libraries (500 bps) will be generated from total genomic DNA derived from cancer samples and subjected to 50 bp, paired end sequencing on the llumina HiSeq 2000. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemias, lymphomas and soft tissue tumors. However, conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution. We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-07-01T12:51:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000088","title":"Familial_Thrombocytosis_germline_exome_sequencing","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 3 relatives from a family with multiple affected familial thrombocytosis (FT) patients.  Germline DNA from 2-4 patients affected with FT will be used to prepare libraries and sequenced in one lane of HiSeq sequencing, mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.","abstract":"Studies of families with multiple affected relatives segregating a disease have proven to be an invaluable resource in the identification of novel disease predisposition genes. A family with strong evidence for familial predisposition to familial  thrombocytosis  will be examined for germline mutations linked to the disease phenotype.  Using Agilent exome hybridisation capture and Illumina HiSeq massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of 2-4 affected relatives with the disease. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with  development of thrombocytosis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-07-05T12:34:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000089","title":"Myelodysplastic_Syndrome_Exome_Sequnecing","description":"Cancer is driven by mutation. Illumina GA massively parallel sequencing technology will be applied to Agilent exome hybridisation capture libraries and total genomic paired-end libraries. Bespoke algorithms are being developed to identify the somatically acquired structural variants, point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with Myelodysplastic Syndrome development.","abstract":"Cancer is driven by mutation. Illumina GA massively parallel sequencing technology will be applied to Agilent exome hybridisation capture libraries and total genomic paired-end libraries. Bespoke algorithms are being developed to identify the somatically acquired structural variants, point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with Myelodysplastic Syndrome development.","study_type":"Other","pubmed_ids":[21995386],"external_links":null,"is_released":true,"released_date":"2011-07-05T12:34:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000090","title":"UK10K COHORT ALSPAC","description":"The UK10K project proposes a series of complementary genetic approaches to find new low-frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome-wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein-coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will directly analyse quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.\n\nThe Avon Longitudinal Study of Parents and Children (ALSPAC) is a two-generation prospective study. Pregnant women living in one of three health districts in the former county of Avon with an expected delivery date between April 1991 and December 1992 were eligible to be enrolled in the study, and this formed the initial point of contact for the development of a large, family based resource.\n\nInformation has been collected on the children and the mothers through retrieval of biological materials (e.g. antenatal blood samples, placentas), biological sampling (e.g. collection of cord blood, umbilical cord, milk teeth, hair, toenails, blood and urine), self-administered questionnaires, data extraction from medical notes, linkage to routine information systems and at repeat research clinics.","abstract":"The UK10K project proposes a series of complementary genetic approaches to find new low-frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome-wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein-coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will directly analyse quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.\n\nThe Avon Longitudinal Study of Parents and Children (ALSPAC) is a two-generation prospective study. Pregnant women living in one of three health districts in the former county of Avon with an expected delivery date between April 1991 and December 1992 were eligible to be enrolled in the study, and this formed the initial point of contact for the development of a large, family based resource.\n\nInformation has been collected on the children and the mothers through retrieval of biological materials (e.g. antenatal blood samples, placentas), biological sampling (e.g. collection of cord blood, umbilical cord, milk teeth, hair, toenails, blood and urine), self-administered questionnaires, data extraction from medical notes, linkage to routine information systems and at repeat research clinics.","study_type":"Other","pubmed_ids":[24676807,25743335,25826619,26315906,26367794,26367797,26368830,27668658,30664637,30692680],"external_links":null,"is_released":true,"released_date":"2011-07-13T13:23:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000091","title":"Grey_Platelet_Syndrome__GPS_","description":"As part of the Bloodomics collaboration we have several categories of pedigrees with diseases/syndromes relevant to cardiovascular diseases (CVD). One such pedigree, Grey Platelet Syndrome (GPS) is a rare congenital bleeding disorder caused by a reduction or absence of alpha granules in platelets. Exome sequencing has been performed as part of a discovery program to ascertain potential causative variants of the clinical phenotype.","abstract":"As part of the Bloodomics collaboration we have several categories of pedigrees with diseases/syndromes relevant to cardiovascular diseases (CVD). 7 cases of Grey Platelet Syndrome (GPS) have been entered in the Exome Seq pipeline. Congenital GPS is an example of an extremely rare disease. It is postulated that the disease is caused by a spectrum of unique sequence variants in as yet non-defined loci. It can be reasoned that the genetic events underlying disease will be of coding nature or a rare copy number variant in a number of cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-07-14T08:22:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000092","title":"Triple_Negative_Breast_Cancer_Whole_Genomes","description":"We propose to definitively characterise the somatic genetics of Triple negative breast cancer through generation of comprehensive catalogues of somatic mutations in 500 cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-07-20T08:48:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000093","title":"Unraveling_the_genetic_basis_of_a_collagen_migration_defect_in_patients_with_a_combined__platelet_dysfunction_and_reduced_bone_density","description":"In this project we study cases from unrelated pedigrees that present at a young age with a phenotype which inludes hypotonia and hypodensity of bones, a chronic elevation of some liver and muscle enzymes as well as abnormal platelet number and volume. We aim to use exome sequencing to discover the causative variants reponsible for these defects.","abstract":"In this study we examine unrelated pedigrees that have a syndromic pheontype of reduced bone density, aberrant platelet formation and neuro-developmental pahology. Cases present at a young age with a variable degree o hypotonia and hypodensity of the bones, in some leading to pathological fractures, and all demonstrating a chronic elevation of some liver and muscle enzymes. There is also evidence of a variable degree of psychomotor retardation with some having epilepsy and/or behavioural problems. We aim to use exome sequencing to discover the causative variants responsible for these defects based on the assumption that the mutations are of a coding nature.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-07-21T12:16:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000094","title":"PREDICT","description":"PREDICT/Predicting individual response and resistance to VEGFR/mTOR pathway therapeutic intervention using biomarkers discovered through tumour functional genomics.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina massively parallel sequencing technology, we aim to sequence microRNAs plus the protein coding genome of a number of samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-07-27T10:32:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000095","title":"Renal_Follow_Up_Series","description":"This study's purpose is to use data generated in Renal whole genome and exome Cancer sequencing to target specific areas in multiple other Renal Cancer samples. These areas will then be subjected to bespoke pull downs, tagged and then pool the resultant amplicons. These amplicons will then be sequenced. This is hoped to show the prevalence of previous findings in multiple individuals in a high throughput method.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-04T14:04:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000096","title":"Identification of improved IL28B SNPs and haplotypes for prediction of drug response in treatment of hepatitis C using massively parallel sequencing in a cross-sectional European cohort","description":"The hepatitis C virus infects nearly 3% of the World’s population, causing severe liver\ndisease in many. Standard of care therapy is currently pegylated interferon alpha and ribavirin\n(PegIFN/R), which is effective in less than half of those infected with the most common viral genotype. Two IL28B SNPs, rs8099917 and rs12979860, predict response to (PegIFN/R) therapy in treatment of hepatitis C virus infection. These SNPs were identified in genome wide analyses using Illumina genotyping chips. In people of European ancestry, there are 6 common (>1%) haplotypes for IL28B, one tagged by rs8099917 minor allele, four tagged by rs12979860.\nWe used massive parallel sequencing of the IL28B and IL28A gene regions generated by PCR \nfrom pooled DNA samples from 100 responders and 99 non-responders to therapy, to identify\ncommon variants. Variants that had high odds ratios and were validated were then genotyped\nin a cohort of 905 responders and non-responders. Their predictive power was assessed, alone\nand in combination with HLA-C. Only SNPs in the IL28B linkage disequilibrium block predicted drug response. Eighteen\nSNPs were identified with evidence for association with drug response, and with a high degree of confidence in the sequence call.\nWe found that two SNPs, rs4803221 (homozygote minor allele positive predictive value (PPV) of 77%) and rs7248668 (PPV 78%), predicted \nfailure to respond better than the current best, rs8099917 (PPV 73%) and rs12979860 (PPV\n68%) in this cross-sectional cohort. The best SNPs tagged a single common haplotype, haplotype 2. Genotypes predicted lack of response better than alleles.\nHowever, combination of IL28B haplotype 2 carrier status with the HLA-C C2C2 genotype, which has previousl y\nbeen reported to improve prediction in combination with IL28B, provides the highest PPV\n(80%). The haplotypes present alternative putative transcription factor binding and\nmethylation sites. Massive parallel sequencing allowed identification and comparison of the best common SNPs \nfor identifying treatment failure in therapy for HCV SNPs tagging a single haplotype have\nthe highest PPV, especially in combination with HLA-C. The functional basis for the association may be due to altered regulation of the gene.\nThese approaches have utility in improving diagnostic testing and identifying causal haplotypes or SNPs.","abstract":"The hepatitis C virus infects nearly 3% of the World’s population, causing severe liverdisease in many. Standard of care therapy is currently pegylated interferon alpha and ribavirin(PegIFN/R), which is effective in less than half of those infected with the most common viral genotype. Two IL28B SNPs, rs8099917 and rs12979860, predict response to (PegIFN/R) therapy in treatment of hepatitis C virus infection. These SNPs were identified in genome wide analyses using Illumina genotyping chips. In people of European ancestry, there are 6 common (&gt;1%) haplotypes for IL28B, one tagged by rs8099917 minor allele, four tagged by rs12979860.We used massive parallel sequencing of the IL28B and IL28A gene regions generated by PCR from pooled DNA samples from 100 responders and 99 non-responders to therapy, to identifycommon variants. Variants that had high odds ratios and were validated were then genotypedin a cohort of 905 responders and non-responders. Their predictive power was assessed, aloneand in combination with HLA-C. Only SNPs in the IL28B linkage disequilibrium block predicted drug response. EighteenSNPs were identified with evidence for association with drug response, and with a high degree of confidence in the sequence call.We found that two SNPs, rs4803221 (homozygote minor allele positive predictive value (PPV) of 77%) and rs7248668 (PPV 78%), predicted failure to respond better than the current best, rs8099917 (PPV 73%) and rs12979860 (PPV68%) in this cross-sectional cohort. The best SNPs tagged a single common haplotype, haplotype 2. Genotypes predicted lack of response better than alleles.However, combination of IL28B haplotype 2 carrier status with the HLA-C C2C2 genotype, which has previousl ybeen reported to improve prediction in combination with IL28B, provides the highest PPV(80%). The haplotypes present alternative putative transcription factor binding andmethylation sites. Massive parallel sequencing allowed identification and comparison of the best common SNPs for identifying treatment failure in therapy for HCV SNPs tagging a single haplotype havethe highest PPV, especially in combination with HLA-C. The functional basis for the association may be due to altered regulation of the gene.These approaches have utility in improving diagnostic testing and identifying causal haplotypes or SNPs.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-05T10:52:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000097","title":"Chromatin_Profiling_in_Twins","description":"50 lymphoblastoid cell lines of adult female Twins which are part of the MuTHER study, processed with the FAIRE assay in order to generate maps of open chromatin.","abstract":"50 lymphoblastoid cell lines of adult female Twins which are part of the MuTHER study, processed with the FAIRE assay in order to generate maps of open chromatin. Sequence variants in these samples will be correlated with FAIRE peaks.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-09T11:45:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000098","title":"Chromatin_Profiling_in_Twins","description":"50 lymphoblastoid cell lines of adult female Twins which are part of the MuTHER study, subjected to  Chromatin Immunoprecipitation  using an antibody for H3K4me1. H3K4me1 peaks mark distal regulatory  elements.","abstract":"50 lymphoblastoid cell lines of adult female Twins which are part of the MuTHER study, subjected to  Chromatin Immunoprecipitation  using an antibody for H3K4me1. H3K4me1 peaks mark distal regulatory  elements. Sequence variants in these samples will be correlated with H3K4me1 peaks.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-09T17:24:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000099","title":"Exome_sequencing_of_a_Novel_Primary_T_Cell_Immunodeficiency_Kindred","description":"Primary T cell immunodeficiency disorders are genetically heterogenous.  Mutations in genes required for specific stages of T cell development within the thymus can lead to reduced numbers of circulating T cells.  On the hand, T cells may not egress from the thymus normally leading to profound T cell lymphopenia.  As a result, patients with these disorders succumb to a range of severe opportunisitic infections unless allogeneic transplantation is performed.  We wish to whole exome sequence a Caucasian family in which the index case shows features of impaired T cell egress from the thymus.  Importantly, known genes implicated in T cell immunodeficiency including CORO1A have been seqeuenced and found to normal in this individual.","abstract":"Primary T cell immunodeficiency disorders are genetically heterogenous.  Mutations in genes required for specific stages of T cell development within the thymus can lead to reduced numbers of circulating T cells.  On the hand, T cells may not egress from the thymus normally leading to profound T cell lymphopenia.  As a result, patients with these disorders succumb to a range of severe opportunisitic infections unless allogeneic transplantation is performed.  We wish to whole exome sequence a Caucasian family in which the index case shows features of impaired T cell egress from the thymus.  Importantly, known genes implicated in T cell immunodeficiency including CORO1A have been seqeuenced and found to normal in this individual.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-11T19:06:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000100","title":"Exome_Sequencing__to_Identify_Causes_of_Leukaemia_Predisposing_Congenital_Neutropenias","description":"The objective of this study is to identify the causative genes in two unrelated congenital neutropenia families.  We aim to whole exome sequence the affected individuals, unaffected siblings and parents in both cases in an effort to idenitfy the causative genetic mutation.  Exome capture will be performed using Agilent SureSelect system.  Subsequently, exome libraries will sequenced using the Illumina HiSeq platform.  Sequence variant calling will be done in house and common variants excluded using public databases and data from unaffected family members.","abstract":"The congenital neutropenias are a heterogeneous group of disorders characterised by low blood neutrophil counts.  Neutropenia can predispose to life-threatening infections and can progress to acute myeloid leukaemia.  Thus identifying the genes associated with neutropenia will not only increase our understanding of normal neutrophil development, but also further our knowledge of leukaemia development.  Although numerous genes have been associated with congenital neutropenia, the genetic basis of around 40% cases remains elusive.  Identification of the causative genetic mutations in these cases has been hampered by the small size of pedigrees, resulting in uninformative genetic linkage studies.  Furthermore, the diverse nature of genes implicated in congenital neutropenia renders candidate gene screening approaches problematic.  Whole exome sequencing provides an alternative way to identify the causative mutations in this heterogeneous disorder.  We wish to sequence the exomes from two unrelated families with neutropenia.  The first Caucasian family comprises congenital neutropenia cases in multiple generations.  To date, genetic linkage studies in this family have been uninformative.  The second family is of consanguineous Asian origin characterised by two affected children, suggestive of an autosomal recessive mode of inheritance.  We propose that an unbiased and comprehensive whole exome sequencing approach will uncover novel genetic mutations responsible for neutropenia in these families.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-11T19:09:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000101","title":"UK10K_RARE_NEUROMUSCULAR","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The neuromuscular disorder samples are part of the “rare disease” group, and will undergo exome sequencing. For further information with regard to this cohort please contact Francesco Muntoni (f.muntoni@ucl.ac.uk).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The neuromuscular disorder samples are part of the “rare disease” group, and will undergo exome sequencing. For further information with regard to this cohort please contact Francesco Muntoni (f.muntoni@ucl.ac.uk).","study_type":"Other","pubmed_ids":[23768512],"external_links":null,"is_released":true,"released_date":"2011-08-16T10:01:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000102","title":"ET_Exome","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 50 Essential Thrombocythemia Myeloproliferative Disease  samples and matched normal DNA from the same patients. Samples will be multiplexed in one  lane of Illumina HiSeq. Sequencing to a coverage of at least 30x will be performed and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina HiSeq massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of 50 matched human Essential Thrombocythemia Myeloproliferative disease samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with Myeloproliferative disease development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-17T13:48:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000103","title":"Genomics_of_Colorectal_Cancer_Metastases___Massively_Parallel_Sequencing_of_Matched_Primary_and_Metastatic_tumours_to_Identify_a_Metastatic_Signature_of_Somatic_Mutations__MOSAIC_","description":"Exome pulldown and SNP6 Affymetrix array of matched primary and metastatic colorectal cancer samples from 20 patients","abstract":": All cancers arise due to the acquisition of somatic mutations in their genomes which fundamentally alter the function of key cancer genes (Stratton et al., 2009). Such mutations are responsible not only for the development of the cancer in the first instance but also in maintaining ongoing proliferation and evasion of cell death that are the hallmarks of many cancers (Hanahan and Weinberg, 2000). A detailed knowledge of such mutational events is critical if we are to understand how cancers develop as well as to design rational therapies to target pathways downstream of these mutational events. Colorectal cancer is the second most common form of cancer, accounting for 13% of all cases in Europe and is also the second largest cause of cancer death. More than 50% of patients diagnosed with colorectal cancer eventually develop metastatic disease and despite improvements in survival with chemotherapy there are no specific genomic lesions in colorectal cancer that are suitable therapeutic targets and that might allow us to begin to stratify patients for treatment based on the presence of a biomarker. This is in contrast to recent advances in the treatment of non-small cell lung cancer and melanoma, where targeting specific genomic alterations with small molecule inhibitors has resulted in dramatic increases in response rates and survival (e.g. EGFR mutations and the EML4-ALK rearrangement in lung cancer and the V600E BRAF mutation in malignant melanoma) (Chapman et al., 2011; Kwak et al., 2010; Mok et al., 2009). Within the last 5 years there has been a revolution in our ability to rapidly sequence cancer genomes in large numbers and at ever greater depth of coverage. We can now determine not only the presence of somatic mutations but also estimate their prevalence in a given sample. A number of research groups, including our own, have published for the first time sequence data for whole cancer exomes and genomes (Pleasance et al., 2009; Varela et al., 2011). Our ability to now map the genomic architecture of clinical samples in exquisite detail using the next-generation of sequencers will facilitate identification of genomic aberrations that play a significant part in the pathophysiology of tumours. Indeed, efforts to systematically sequence large numbers of primary tumours are already underway as part of the International Cancer Genome Consortium (Hudson et al., 2010). An intriguing and important clinical question is to what extent analysis of primary tumour will reveal oncogenic mutations that are also important for cancer cell survival in the metastatic setting. The majority of patients in the setting of colorectal cancer (and indeed in most solid tumours) ultimately die as a result of metastatic disease. Recently published data in the setting of breast cancer has shown that metastases not only accumulate new mutations but also become enriched for low-frequency mutations that are detectable in the primary tumour, raising the possibility that sequencing metastases in addition to primary tumour will uncover additional driver mutations that may be important therapeutic targets or prognostic indicators (Ding et al., 2010). With the advent of next-generation sequencing technologies we can now compare genome-wide alterations between matched primary and metastatic cancer genomes in order to determine which events may be critical for the development and maintenance of the metastatic process and potentially, which of these are therapeutic targets. We propose therefore to generate complete catalogues of somatic mutations and copy number alterations in 20 matched primary and metastatic colorectal cancers by high-coverage, shotgun exome sequencing and through the use of SNP arrays. These approaches will identify the presence of genomic aberrations including substitutions, insertions/deletions and copy number changes. In particular, we propose to identify those mutations that are significantly enriched for in the metastases as being most likely to be involved in either the development of the metastatic phenotype or actively involved in the pathophysiology of the metastatic cancer cell. Confirmation of all putative somatic mutations will be carried out by targeted PCR and sequencing on an orthogonal platform using an independent cohort of additional tumour samples. We propose to explore the extent to which somatic mutations identified as recurrent in the metastatic setting are able to subvert normal biological processes using genetically engineered mouse models and established cancer cell lines.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-17T13:51:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000104","title":"Hyperfibrinolysis","description":"As part of the Bloodomics collaboration we have several categories of pedigrees with diseases/syndromes relevant to cardiovascular diseases (CVD). One such pedigree, hyperfibrinolysis is associated with increased fibrinolytic activity, resulting in increased bleeding.  Exome sequencing has been performed as part of a discovery program to ascertain potential causative variants of the clinical phenotype.","abstract":"As part of the Bloodomics collaboration we have several categories of pedigrees with diseases/syndromes relevant to cardiovascular diseases (CVD). 3 cases of hyperfibrinolysis have been entered in the Exome Seq pipeline. Inherited hyperfibrinolysis is an example of an extremely rare disease. It is postulated that the disease is caused by a spectrum of unique sequence variants in as yet non-defined loci. It can be reasoned that the genetic events underlying disease will be of coding nature or a rare copy number variant in a number of cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-17T15:04:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000105","title":"Platelet_collagen_defect","description":"As part of the Bloodomics collaboration we have several categories of pedigrees with diseases/syndromes relevant to cardiovascular diseases (CVD). One such pedigree, is from families who have a platelet collagen defect.  Exome sequencing has been performed as part of a discovery program to ascertain potential causative variants of the clinical phenotype.","abstract":"As part of the Bloodomics collaboration we have several categories of pedigrees with diseases/syndromes relevant to cardiovascular diseases (CVD). 8 cases of platelet collagen defect have been entered in the Exome Seq pipeline. Platelet collagen defects are examples of an extremely rare disease. It is postulated that the disease is caused by a spectrum of unique sequence variants in as yet non-defined loci. It can be reasoned that the genetic events underlying disease will be of coding nature or a rare copy number variant in a number of cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-17T15:05:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000106","title":"Bleeding","description":"As part of the Bloodomics collaboration we have several categories of pedigrees with diseases/syndromes relevant to cardiovascular diseases (CVD). One such group, is from individuals who exhibit severe bleeding with an unknown cause.  Exome sequencing has been performed as part of a discovery program to ascertain potential causative variants of the clinical phenotype.","abstract":"As part of the Bloodomics collaboration we have several categories of pedigrees with diseases/syndromes relevant to cardiovascular diseases (CVD). 3 cases of severe bleeding have been entered in the Exome Seq pipeline. Defects that cause severe bleeding are extremely rare. It is postulated that the disease is caused by a spectrum of unique sequence variants in as yet non-defined loci. It can be reasoned that the genetic events underlying disease will be of coding nature or a rare copy number variant in a number of cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-17T15:06:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000107","title":"Various_Platelet_Disorders","description":"As part of the Bloodomics collaboration we have several categories of pedigrees with diseases/syndromes relevant to cardiovascular diseases (CVD). One such group, is from individuals who have a platelet disorder with an unknown cause.  Exome sequencing has been performed as part of a discovery program to ascertain potential causative variants of the clinical phenotype.","abstract":"As part of the Bloodomics collaboration we have several categories of pedigrees with diseases/syndromes relevant to cardiovascular diseases (CVD). 4 cases of platelet disorders which include patients with thrombocytopenia, Roifman syndrome, Giant platelets and hyper Gs funcion have been entered in the Exome Seq pipeline. Defects that cause such platelet disorders are extremely rare. It is postulated that the disease is caused by a spectrum of unique sequence variants in as yet non-defined loci. It can be reasoned that the genetic events underlying disease will be of coding nature or a rare copy number variant in a number of cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-17T15:06:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000108","title":"UK10K COHORT TWINSUK","description":"The UK10K project proposes a series of complementary genetic approaches to find new low-frequency/rare variants contributing to disease phenotypes.  These will be based on obtaining the genome-wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein-coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes.  Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing.  We will directly analyse quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.  \n\nThe TwinsUK samples will be part of the cohort study and will undergo whole genome sequencing. For further information with regard to this cohort please contact Brent Richards (brent.richards@kcl.ac.uk) or Nicole Soranzo (ns6@sanger.ac.uk).","abstract":"The UK10K project proposes a series of complementary genetic approaches to find new low-frequency/rare variants contributing to disease phenotypes.  These will be based on obtaining the genome-wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein-coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes.  Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing.  We will directly analyse quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.  \n\nThe TwinsUK samples will be part of the cohort study and will undergo whole genome sequencing. For further information with regard to this cohort please contact Brent Richards (brent.richards@kcl.ac.uk) or Nicole Soranzo (ns6@sanger.ac.uk).","study_type":"Other","pubmed_ids":[24343240,25743335,25826619,26315906,26367794,26367797,26368830,27668658,30664637],"external_links":null,"is_released":true,"released_date":"2011-08-18T13:49:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000109","title":"UK10K NEURO ABERDEEN","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. This sample set comprises cases of schizophrenia with additional cognitive measurements, collected in Aberdeen, Scotland.For further information on the Aberdeen cohort please contact David St Clair (d.stclair@abdn.ac.uk).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. This sample set comprises cases of schizophrenia with additional cognitive measurements, collected in Aberdeen, Scotland.For further information on the Aberdeen cohort please contact David St Clair (d.stclair@abdn.ac.uk).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T13:51:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000110","title":"UK10K_NEURO_ASD_FI","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.These samples are a subset of a nationwide collection of Finnish autism spectrum disorder (ASD) samples.  The samples have been collected from Central Hospitals across Finland in collaboration with the University of Helsinki. The samples consist of 93 individuals with a diagnosis of autistic disorder or Asperger syndrome from 36 families with at least two affected individuals.  Of these individuals, 16 can be genealogically connected to form two large pedigrees originating from Central Finland, suggesting possible genetic risk factors shared identical by descent within the pedigrees. All diagnoses are based on ICD-10 and DSM-IV diagnostic criteria for ASDs. Additional phenotypic data is available for a subset of the individuals.For further information with regard to this cohort please contact Aarno Palotie (Aarno.palotie@helsinki.fi).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.These samples are a subset of a nationwide collection of Finnish autism spectrum disorder (ASD) samples.  The samples have been collected from Central Hospitals across Finland in collaboration with the University of Helsinki. The samples consist of 93 individuals with a diagnosis of autistic disorder or Asperger syndrome from 36 families with at least two affected individuals.  Of these individuals, 16 can be genealogically connected to form two large pedigrees originating from Central Finland, suggesting possible genetic risk factors shared identical by descent within the pedigrees. All diagnoses are based on ICD-10 and DSM-IV diagnostic criteria for ASDs. Additional phenotypic data is available for a subset of the individuals.For further information with regard to this cohort please contact Aarno Palotie (Aarno.palotie@helsinki.fi).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:27:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000111","title":"UK10K NEURO ASD BIONED","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The BioNED (Biomarkers for Childhood onset neuropsychiatric disorders) study has been carrying out detailed phenotypic assessments evaluating children with an autism spectrum disorder. These assessments included ADI-R, ADOS, neuropsychology, EEG etc. There are 56 DNA samples from this study (25 extracted from blood). For further information with regard to this cohort please contact Patrick Bolton (patrick.bolton@kcl.ac.uk).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The BioNED (Biomarkers for Childhood onset neuropsychiatric disorders) study has been carrying out detailed phenotypic assessments evaluating children with an autism spectrum disorder. These assessments included ADI-R, ADOS, neuropsychology, EEG etc. There are 56 DNA samples from this study (25 extracted from blood). For further information with regard to this cohort please contact Patrick Bolton (patrick.bolton@kcl.ac.uk).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:27:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000112","title":"UK10K NEURO ASD GALLAGHER","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. This is an Irish sample set of individuals with ASD (approximately 50% with comorbid intellectual disability). Individuals have been diagnosed with ADI/ ADOS, measures of cognition/ adaptive function. They represent a more severe, narrowly defined cohort of ASD subjects. Family histories are available for some with measures of broader phenotype. For further information on this cohort please contact Nadia Bolshakova (bolshakn@tcd.ie).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. This is an Irish sample set of individuals with ASD (approximately 50% with comorbid intellectual disability). Individuals have been diagnosed with ADI/ ADOS, measures of cognition/ adaptive function. They represent a more severe, narrowly defined cohort of ASD subjects. Family histories are available for some with measures of broader phenotype. For further information on this cohort please contact Nadia Bolshakova (bolshakn@tcd.ie).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:28:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000113","title":"UK10K NEURO ASD MGAS","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.  The MGAS (Molecular Genetics of Autism Study) samples are from a clinical sample seen by specialists at the Maudsley hospital and who have had detailed phenotypic assessments with ADI-R and ADOS.For further information on this cohort please contact Patrick Bolton (patrick.bolton@kcl.ac.uk).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.  The MGAS (Molecular Genetics of Autism Study) samples are from a clinical sample seen by specialists at the Maudsley hospital and who have had detailed phenotypic assessments with ADI-R and ADOS.For further information on this cohort please contact Patrick Bolton (patrick.bolton@kcl.ac.uk).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:29:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000114","title":"UK10K NEURO ASD SKUSE","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. This sample set of UK origin consists of clinically identified subjects with Autism Spectrum Disorders, mostly without intellectual disability (ie. Verbal IQs &gt;70). The subjects represent children and adults with Autism, Asperger syndrome or Atypical Autism, identified according to standardized research criteria (ADI-algorithm, ADOS). A minority has identified comorbid neurodevelopmental disorders (e.g. ADHD). Family histories are available, with measures of broader phenotype in first-degree relatives.For further information on this cohort please contact David Skuse (d.skuse@ucl.ac.uk).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. This sample set of UK origin consists of clinically identified subjects with Autism Spectrum Disorders, mostly without intellectual disability (ie. Verbal IQs &gt;70). The subjects represent children and adults with Autism, Asperger syndrome or Atypical Autism, identified according to standardized research criteria (ADI-algorithm, ADOS). A minority has identified comorbid neurodevelopmental disorders (e.g. ADHD). Family histories are available, with measures of broader phenotype in first-degree relatives.For further information on this cohort please contact David Skuse (d.skuse@ucl.ac.uk).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:30:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000115","title":"UK10K NEURO ASD TAMPERE","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The Tampere Autism sample set consists of samples from Finnish subjects with ASD (autism spectrum disorders) with IQs over 70 recruited from a clinical centre for the diagnosis and treatment of children with ASD. For further information on this cohort please contact either Terho Lehtimaki (terho.lehtimaki@uta.fi) or Kaija Puura (kaija.puura@pshp.fi).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The Tampere Autism sample set consists of samples from Finnish subjects with ASD (autism spectrum disorders) with IQs over 70 recruited from a clinical centre for the diagnosis and treatment of children with ASD. For further information on this cohort please contact either Terho Lehtimaki (terho.lehtimaki@uta.fi) or Kaija Puura (kaija.puura@pshp.fi).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:31:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000116","title":"UK10K NEURO ASD TEDS","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The TEDS sample set comes from an epidemiological study, the “Twins Early Development Study”, which were screened for ASD (autism spectrum disorders). Those screened positive were investigated for categorical ASD in a study called the SRS (Social Responsiveness study). Twins (MZ and DZ) with a categorical dx ASD are included.","abstract":"The TEDS sample( N~140) comes from an epidemiological study, the twins early development study, which were screened for ASD. Those screen positive were investigated for categorical ASD in a study called the SRS (Social Responsiveness study). Twins (MZ and DZ) with a categorical dx ASD will be included for transfer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000117","title":"UK10K NEURO EDINBURGH","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. This sample set consists of subjects with schizophrenia recruited from psychiatric in-patient and out-patient facilities in Scotland. All diagnoses are based on standard research procedures and family histories are available. Patients have IQ&gt;70 and the cohort includes the following groups: 100 cases with detailed clinical, cognitive and structural and functional neuroimaging phenotypes; 138 familial cases who are the probands of families where DNA has been collected from other affected members; 162 unrelated individuals. In most cases patients and their families may be re contacted to take part in further studies.For further information on this cohort please contact Andrew McIntosh (andrew.mcintosh@ed.ac.uk).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. This sample set consists of subjects with schizophrenia recruited from psychiatric in-patient and out-patient facilities in Scotland. All diagnoses are based on standard research procedures and family histories are available. Patients have IQ&gt;70 and the cohort includes the following groups: 100 cases with detailed clinical, cognitive and structural and functional neuroimaging phenotypes; 138 familial cases who are the probands of families where DNA has been collected from other affected members; 162 unrelated individuals. In most cases patients and their families may be re contacted to take part in further studies.For further information on this cohort please contact Andrew McIntosh (andrew.mcintosh@ed.ac.uk).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:33:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000118","title":"UK10K NEURO FSZ","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing.  We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. These Finnish schizophrenia samples have been collected from a population cohort using national registers. The entire sample collection consists of 2756 individuals from 458 families of whom 931 are diagnosed with schizophrenia spectrum disorder, each family having at least two affected siblings. 170 families originate from an internal isolate (Kuusamo) with a three-fold lifetime risk for the trait. The genealogy of the internal isolate is well documented and the individuals form a “megapedigree” reaching to the 17th Century. All diagnoses are based on DSM-IV and for a large fraction of cases there is cognitive data. For further details/descriptions with regard to this data set please contact Tiina Paunio (tiina.paunio@thl.fi)","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing.  We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. These Finnish schizophrenia samples have been collected from a population cohort using national registers. The entire sample collection consists of 2756 individuals from 458 families of whom 931 are diagnosed with schizophrenia spectrum disorder, each family having at least two affected siblings. 170 families originate from an internal isolate (Kuusamo) with a three-fold lifetime risk for the trait. The genealogy of the internal isolate is well documented and the individuals form a “megapedigree” reaching to the 17th Century. All diagnoses are based on DSM-IV and for a large fraction of cases there is cognitive data. For further details/descriptions with regard to this data set please contact Tiina Paunio (tiina.paunio@thl.fi)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:34:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000119","title":"UK10K NEURO FSZNK","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. This Finnish schizophrenia sample set has been collected from a population cohort using national registers. The entire sample collection consists of 2756 individuals from 458 families of whom 931 are diagnosed with schizophrenia spectrum disorder. Families outside Kuusamo (n=288) all had at least two affected siblings. All diagnoses are based on DSM-IV and for a large fraction of cases there is cognitive data.For further details/descriptions with regard to this data set please contact Tiina Paunio (tiina.paunio@thl.fi)","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. This Finnish schizophrenia sample set has been collected from a population cohort using national registers. The entire sample collection consists of 2756 individuals from 458 families of whom 931 are diagnosed with schizophrenia spectrum disorder. Families outside Kuusamo (n=288) all had at least two affected siblings. All diagnoses are based on DSM-IV and for a large fraction of cases there is cognitive data.For further details/descriptions with regard to this data set please contact Tiina Paunio (tiina.paunio@thl.fi)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:35:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000120","title":"UK10K NEURO IMGSAC","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.The IMGSAC cohort is an international collection of families containing children ascertained for ASDs (autism spectrum disorders). The affected individuals are have been phenotyped, including using the ADI-R and ADOS instruments. Individuals with a past or current medical disorder of probable etiological significance or TSC have been excluded. Where possible, karyotyping has been performed on one affected individual per family to exclude Fragile X syndrome. Many of the samples have been genotyped, using the Affymetrix 10k and Illumina 1M platforms. All samples to be included in the current study are of UK origin.For further information on this cohort please contact Jeremy Parr (jeremy.parr@newcastle.ac.uk).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.The IMGSAC cohort is an international collection of families containing children ascertained for ASDs (autism spectrum disorders). The affected individuals are have been phenotyped, including using the ADI-R and ADOS instruments. Individuals with a past or current medical disorder of probable etiological significance or TSC have been excluded. Where possible, karyotyping has been performed on one affected individual per family to exclude Fragile X syndrome. Many of the samples have been genotyped, using the Affymetrix 10k and Illumina 1M platforms. All samples to be included in the current study are of UK origin.For further information on this cohort please contact Jeremy Parr (jeremy.parr@newcastle.ac.uk).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:36:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000121","title":"UK10K NEURO IOP COLLIER","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The Genetics and Psychosis (GAP) set consists of samples from subjects with schizophrenia, ascertained as a new-onset sample. This set is of UK origin, with data on cognition, brain imaging and other endophenotypes. The Maudsley twin series consists of probands ascertained from the Maudsley Twin Register, defined as patients of multiple birth who had suffered psychotic symptoms. This set is of UK origin, with data on cognition, brain imaging and other endophenotypes, with DNA available from an MZ or DZ affected or unaffected co-twin. The Maudsley family study (MFS) consists of over 250 families who have a history of schizophrenia or bipolar disorder Within the Maudsley Family Study, biological markers of psychosis include neuropsychological tests, Evoked Response Potentials Tests (ERPs), MRI scans, dermatoglyphics and eye tracking. Early risk factors for psychosis and clinical symptoms are also investigated.  This set is of UK origin, with DNA available from both affected and unaffected relatives in many of the probands. For further information on this study please contact David Collier (david.collier@kcl.ac.uk).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The Genetics and Psychosis (GAP) set consists of samples from subjects with schizophrenia, ascertained as a new-onset sample. This set is of UK origin, with data on cognition, brain imaging and other endophenotypes. The Maudsley twin series consists of probands ascertained from the Maudsley Twin Register, defined as patients of multiple birth who had suffered psychotic symptoms. This set is of UK origin, with data on cognition, brain imaging and other endophenotypes, with DNA available from an MZ or DZ affected or unaffected co-twin. The Maudsley family study (MFS) consists of over 250 families who have a history of schizophrenia or bipolar disorder Within the Maudsley Family Study, biological markers of psychosis include neuropsychological tests, Evoked Response Potentials Tests (ERPs), MRI scans, dermatoglyphics and eye tracking. Early risk factors for psychosis and clinical symptoms are also investigated.  This set is of UK origin, with DNA available from both affected and unaffected relatives in many of the probands. For further information on this study please contact David Collier (david.collier@kcl.ac.uk).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:37:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000122","title":"UK10K_NEURO_MUIR","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.The sample selection consists of subjects with schizophrenia (SZ), autism, or other psychoses all with mental retardation (learning disability). The samples were initially collected under the leadership of Walter J Muir (deceased), now with Prof. Blackwood, Dr McKechanie and Prof McIntosh as custodians. These subjects represent the intersection of severe forms of neurodevelopmental disorders, appear to have a higher rate of familiality of SZ than typical, and are likely to have more serious and penetrant forms of mutations.For further information on this cohort please contact Andrew McIntosh (andrew.mcintosh@ed.ac.uk).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.The sample selection consists of subjects with schizophrenia (SZ), autism, or other psychoses all with mental retardation (learning disability). The samples were initially collected under the leadership of Walter J Muir (deceased), now with Prof. Blackwood, Dr McKechanie and Prof McIntosh as custodians. These subjects represent the intersection of severe forms of neurodevelopmental disorders, appear to have a higher rate of familiality of SZ than typical, and are likely to have more serious and penetrant forms of mutations.For further information on this cohort please contact Andrew McIntosh (andrew.mcintosh@ed.ac.uk).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:38:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000123","title":"UK10K NEURO UKSCZ","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. These samples have been collected from throughout the UK and Ireland. The samples fall into two main categories, approximately 500 have a full diagnostic work up. A proportion of these are cases with a positive family history of schizophrenia, either collected as sib-pairs or from multiplex kindred's. The second group consist mainly of  &gt;300 samples that have been systematically collected within South Wales and in addition to full diagnostic work up have undergone detailed cognitive testing. All samples have obtained a DSM IV diagnosis of schizophrenia or schizoaffective disorder.For further information on this cohort please contact Michael Owen (OwenMJ@cardiff.ac.uk).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. These samples have been collected from throughout the UK and Ireland. The samples fall into two main categories, approximately 500 have a full diagnostic work up. A proportion of these are cases with a positive family history of schizophrenia, either collected as sib-pairs or from multiplex kindred's. The second group consist mainly of  &gt;300 samples that have been systematically collected within South Wales and in addition to full diagnostic work up have undergone detailed cognitive testing. All samples have obtained a DSM IV diagnosis of schizophrenia or schizoaffective disorder.For further information on this cohort please contact Michael Owen (OwenMJ@cardiff.ac.uk).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:38:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000124","title":"UK10K_OBESITY_SCOOP","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.The SCOOP samples are part of the Obesity group and will undergo exome sequencing. Severe Childhood Onset Obesity Project (SCOOP) is a sub-cohort of the Genetics Of Obesity Study (GOOS) cohort established by Sadaf Farooqi and Steve O’Rahilly at the University of Cambridge over the last 12 years. The GOOS cohort contains &gt;4,000 patients of diverse geographic origin, many of whom have monogenic and syndromic forms of obesity, and includes patients that are offspring of consanguineous union. SCOOP is a subset of &gt;1500 UK Caucasian patients with severe, early onset obesity (all patients have a BMI Standard Deviation Score (SDS) &gt; 3 and obesity onset before the age of 10 years), in whom all known monogenic causes of obesity have been excluded.  GWAS data on the SCOOP cohort will be available (WTCCC2 independent study) at the time of the start of this study. Data from this cohort has demonstrated that the prevalence of the common obesity risk alleles in FTO, MC4R and NEGR1 are amongst the highest within SCOOP, demonstrating its value also in the study of genetic variants with an impact on more common obesity. For further information with regard to this cohort please contact Sadaf Farooqi (isf20@medschl.cam.ac.uk).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.The SCOOP samples are part of the Obesity group and will undergo exome sequencing. Severe Childhood Onset Obesity Project (SCOOP) is a sub-cohort of the Genetics Of Obesity Study (GOOS) cohort established by Sadaf Farooqi and Steve O’Rahilly at the University of Cambridge over the last 12 years. The GOOS cohort contains &gt;4,000 patients of diverse geographic origin, many of whom have monogenic and syndromic forms of obesity, and includes patients that are offspring of consanguineous union. SCOOP is a subset of &gt;1500 UK Caucasian patients with severe, early onset obesity (all patients have a BMI Standard Deviation Score (SDS) &gt; 3 and obesity onset before the age of 10 years), in whom all known monogenic causes of obesity have been excluded.  GWAS data on the SCOOP cohort will be available (WTCCC2 independent study) at the time of the start of this study. Data from this cohort has demonstrated that the prevalence of the common obesity risk alleles in FTO, MC4R and NEGR1 are amongst the highest within SCOOP, demonstrating its value also in the study of genetic variants with an impact on more common obesity. For further information with regard to this cohort please contact Sadaf Farooqi (isf20@medschl.cam.ac.uk).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:40:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000125","title":"UK10K RARE CHD","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The CHD (congenital heart disease) samples will be part of the “rare disease” group, and will undergo exome sequencing.For further information with regard to this cohort please contact Shoumo Bhattacharya (shoumo@me.com).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The CHD (congenital heart disease) samples will be part of the “rare disease” group, and will undergo exome sequencing.For further information with regard to this cohort please contact Shoumo Bhattacharya (shoumo@me.com).","study_type":"Other","pubmed_ids":[24702954],"external_links":null,"is_released":true,"released_date":"2011-08-18T14:41:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000126","title":"UK10K_RARE_CILIOPATHIES","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing.  We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. \nThe Ciliopathies samples will be part of the rare disease group, and will undergo exome sequencing. For further information with regard to this cohort please contact Phil Beales (p.beales@ich.ucl.ac.uk).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing.  We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. \nThe Ciliopathies samples will be part of the rare disease group, and will undergo exome sequencing. For further information with regard to this cohort please contact Phil Beales (p.beales@ich.ucl.ac.uk).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:41:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000127","title":"UK10K RARE COLOBOMA","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing.  We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. Ocular coloboma is the most common significant developmental eye defect with an incidence of ~1 in 5,000 live births. It results from failure of optic fissure closure during embryogenesis. The position and extent of the fusion failure dictates the clinical appearance and functional effect. ~30% of coloboma cases are associated with other systemic malformations. These UK10K samples will mostly comprise isolated coloboma cases without systemic involvement (aka non-syndromal coloboma). There is strong evidence from family studies that coloboma has a major genetic component with autosomal dominance being the most common pattern of inheritance. However, many cases are isolated or show complex patterns of familial clustering. The genes responsible for isolated coloboma are largely unknown, but in a small number of families mutations in SHH, CHX10, and PAX6 have been identified indicating marked genetic heterogeneity. Thus in addition to the clinical benefits of achieving a molecular diagnosis there are also major scientific advantages to identifying coloboma genes, as these are likely to provide insights into the complex process of optic fissure closure, that is critical to normal eye development. In the longer term, understanding the molecular basis of the disease may provide clues to therapeutic strategies.For further information with regard to this cohort please contact David Fitzpatrick (david.fitzpatrick@ed.ac.uk).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing.  We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. Ocular coloboma is the most common significant developmental eye defect with an incidence of ~1 in 5,000 live births. It results from failure of optic fissure closure during embryogenesis. The position and extent of the fusion failure dictates the clinical appearance and functional effect. ~30% of coloboma cases are associated with other systemic malformations. These UK10K samples will mostly comprise isolated coloboma cases without systemic involvement (aka non-syndromal coloboma). There is strong evidence from family studies that coloboma has a major genetic component with autosomal dominance being the most common pattern of inheritance. However, many cases are isolated or show complex patterns of familial clustering. The genes responsible for isolated coloboma are largely unknown, but in a small number of families mutations in SHH, CHX10, and PAX6 have been identified indicating marked genetic heterogeneity. Thus in addition to the clinical benefits of achieving a molecular diagnosis there are also major scientific advantages to identifying coloboma genes, as these are likely to provide insights into the complex process of optic fissure closure, that is critical to normal eye development. In the longer term, understanding the molecular basis of the disease may provide clues to therapeutic strategies.For further information with regard to this cohort please contact David Fitzpatrick (david.fitzpatrick@ed.ac.uk).","study_type":"Other","pubmed_ids":[24906020,25719200],"external_links":null,"is_released":true,"released_date":"2011-08-18T14:42:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000128","title":"UK10K_RARE_FIND","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The Raymond samples will be part of the “rare disease” group, and will undergo exome sequencing. For further information with regard to this cohort please contact Lucy Raymond (flr24@cam.ac.uk).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The Raymond samples will be part of the “rare disease” group, and will undergo exome sequencing. For further information with regard to this cohort please contact Lucy Raymond (flr24@cam.ac.uk).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:42:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000129","title":"UK10K_RARE_HYPERCHOL","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.Familial Hypercholesterolemia is a condition where the affected person has a consistently high level of LDL which can lead to early clogging of the coronary arteries. All patients selected for this study will have been found not to carry the common APOB and PCSK9 mutations, and to have no detectable LDLR mutations by testing for 18 common mutations. For further information with regard to this cohort please contact Steve Humphries(steve.humphries@ucl.ac.uk).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.Familial Hypercholesterolemia is a condition where the affected person has a consistently high level of LDL which can lead to early clogging of the coronary arteries. All patients selected for this study will have been found not to carry the common APOB and PCSK9 mutations, and to have no detectable LDLR mutations by testing for 18 common mutations. For further information with regard to this cohort please contact Steve Humphries(steve.humphries@ucl.ac.uk).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:43:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000130","title":"UK10K_RARE_SIR","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes.Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.The SIR (Severe Insulin Resistance) samples are part of the “rare disease” group, and will undergo exome sequencing. For further information with regard to this cohort please contact Robert Semple (rks16@cam.ac.uk).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes.Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.The SIR (Severe Insulin Resistance) samples are part of the “rare disease” group, and will undergo exome sequencing. For further information with regard to this cohort please contact Robert Semple (rks16@cam.ac.uk).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:44:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000131","title":"UK10K_RARE_THYROID","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.Two cohorts of subjects are being analysed: Individuals with Congenital Hypothyroidism (CH) due either to dysgenesis or dyshormonogenesis; Patients with Resistance to Thyroid hormone (RTH), a disorder characterized by elevated thyroid hormones and variable tissue refractoriness to hormone action. The CH cohort has been enriched for genetic aetiologies by recruiting cases that are familial, on a consanguineous background or syndromic. The RTH cohort consists of cases in which candidate gene analyses have been negative.For further information with regard to this cohort please contact Krishna Chatterjee (kkc1@medschl.cam.ac.uk).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.Two cohorts of subjects are being analysed: Individuals with Congenital Hypothyroidism (CH) due either to dysgenesis or dyshormonogenesis; Patients with Resistance to Thyroid hormone (RTH), a disorder characterized by elevated thyroid hormones and variable tissue refractoriness to hormone action. The CH cohort has been enriched for genetic aetiologies by recruiting cases that are familial, on a consanguineous background or syndromic. The RTH cohort consists of cases in which candidate gene analyses have been negative.For further information with regard to this cohort please contact Krishna Chatterjee (kkc1@medschl.cam.ac.uk).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-18T14:45:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000132","title":"The clonal and mutational evolution spectrum of primary triple negative breast cancers","description":"Primary triple negative breast cancers (TNBC) represent approximately 16% of all breast cancers and are a tumour type defined by exclusion,for which comprehensive landscapes of somatic mutation have not been determined. Here we show in 104 early TNBC cases, that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some exhibiting only a handful of somatic aberrations in a few pathways, whereas others contain hundreds of somatic events and multiple pathways implicated. Integration with matched whole transcriptome sequence data revealed that only 36% of mutations are expressed.  By examining single nucleotide variant (SNV) allelic abundance derived from deep re-sequencing (median &gt; 20,000 fold) measurements in 2414 somatic mutations, we determine for the first time in an epithelial tumour, the relative abundance of clonal genotypes among cases in the population. We show that TNBC vary widely and continuously in their clonal frequencies at the time of diagnosis, with basal subtype TNBC exhibiting more variation than non-basal TNBC. Although p53 and  somatic mutations appear clonally dominant compared with other pathways, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal and cell shape/motility proteins occurred at lower clonal frequencies, suggesting they occurred later during tumour progression.  Taken together our results show that future attempts to dissect the biology and therapeutic responses of TNBC will require the determination of individual tumour clonal genotypes.","abstract":"Primary triple negative breast cancers (TNBC) represent approximately 16% of all breast cancers and are a tumour type defined by exclusion,for which comprehensive landscapes of somatic mutation have not been determined. Here we show in 104 early TNBC cases, that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some exhibiting only a handful of somatic aberrations in a few pathways, whereas others contain hundreds of somatic events and multiple pathways implicated. Integration with matched whole transcriptome sequence data revealed that only 36% of mutations are expressed.  By examining single nucleotide variant (SNV) allelic abundance derived from deep re-sequencing (median &gt; 20,000 fold) measurements in 2414 somatic mutations, we determine for the first time in an epithelial tumour, the relative abundance of clonal genotypes among cases in the population. We show that TNBC vary widely and continuously in their clonal frequencies at the time of diagnosis, with basal subtype TNBC exhibiting more variation than non-basal TNBC. Although p53 and  somatic mutations appear clonally dominant compared with other pathways, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal and cell shape/motility proteins occurred at lower clonal frequencies, suggesting they occurred later during tumour progression.  Taken together our results show that future attempts to dissect the biology and therapeutic responses of TNBC will require the determination of individual tumour clonal genotypes.","study_type":"Exome Sequencing","pubmed_ids":[22495314,22637570,24845652],"external_links":null,"is_released":true,"released_date":"2011-08-18T20:24:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000133","title":"Genetic_factors_underlying_premature_coronary_heart_disease_in_patients_with_normal_coronary_arteries","description":"The study will analyse by exome sequencing 42 Greek patients with premature MI and no vessel disease to identify genetic factors underlying this condition.","abstract":"Young adults are a relatively small proportion of patients who sustain acute myocardial infarction [MI]; patients under  the age of 45 years make up between 5-10% of all MIs and have a different risk factor profile compared to older patients. In particular, young survivors of MI are characterized by a higher proportion of heavy smoking and family history of coronary heart disease and a lower proportion of hypertension and diabetes mellitus.  A distinct characteristic of premature MI is the relatively high proportion of angiographically “normal” or near “normal” coronary arteries.  The study will analyse by exome sequencing 42 Greek patients with premature MI and no vessel disease to identify genetic factors underlying this condition.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-22T13:28:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000134","title":"An_evaluation_of_different_strategies_for_large_scale_pooled_sequencing_study_design_","description":"Second generation sequencing technology has enabled the design of large-scale sequencing experiments in targeted disease-related regions in thousands of cases and controls. Cost implications dictate a pooled DNA sequencing design, evaluation of allele frequency differences based on the resequenced samples and large-scale targeted follow-up in further samples. To evaluate the feasibility of this approach and to assess different study design strategies, we have carried out a pilot study which tests the feasibility of PCR-based and pull-down DNA pooling for (a) SNP discovery and (b) allele frequency comparison purposes. All samples are from the HapMap or 1958 BC. The sample composition of the pool is listed below: Pool 5: 31 HapMap Individuals (NA12249, NA12156, NA12004, NA11831, NA12716, NA11832, NA11993, NA12057, NA11995, NA12006, NA12144, NA12802, NA12146, NA12005, NA12003, NA07000, NA12043, NA12044, NA11992, NA11881, NA11994, NA07345, NA12154, NA06994, NA06985, NA12239, NA07022, NA07034, NA12155, NA07056, NA06993); 19 1958 BC Individuals (WTCCC88214, WTCCC88215, WTCCC88216, WTCCC88217, WTCCC88222, WTCCC88233, WTCCC88240, WTCCC88241, WTCCC88242, WTCCC88247, WTCCC88249, WTCCC88262, WTCCC88264, WTCCC88278, WTCCC88294, WTCCC88298, WTCCC88302, WTCCC88305, WTCCC88321) Some pools were carried out in duplicate to assess reproducibility. We focused on 10 (PD), 7(PCR) chromosomal regions, ~2(PD), ~1.6 (PCR) Mb in total.","abstract":"Second generation sequencing technology has enabled the design of large-scale sequencing experiments in targeted disease-related regions in thousands of cases and controls. Cost implications dictate a pooled DNA sequencing design, evaluation of allele frequency differences based on the resequenced samples and large-scale targeted follow-up in further samples. To evaluate the feasibility of this approach and to assess different study design strategies, we have carried out a pilot study which tests the feasibility of PCR-based and pull-down DNA pooling for (a) SNP discovery and (b) allele frequency comparison purposes. All samples are from the HapMap or 1958 BC. The sample composition of the pool is listed below: Pool 5: 31 HapMap Individuals (NA12249, NA12156, NA12004, NA11831, NA12716, NA11832, NA11993, NA12057, NA11995, NA12006, NA12144, NA12802, NA12146, NA12005, NA12003, NA07000, NA12043, NA12044, NA11992, NA11881, NA11994, NA07345, NA12154, NA06994, NA06985, NA12239, NA07022, NA07034, NA12155, NA07056, NA06993); 19 1958 BC Individuals (WTCCC88214, WTCCC88215, WTCCC88216, WTCCC88217, WTCCC88222, WTCCC88233, WTCCC88240, WTCCC88241, WTCCC88242, WTCCC88247, WTCCC88249, WTCCC88262, WTCCC88264, WTCCC88278, WTCCC88294, WTCCC88298, WTCCC88302, WTCCC88305, WTCCC88321) Some pools were carried out in duplicate to assess reproducibility. We focused on 10 (PD), 7(PCR) chromosomal regions, ~2(PD), ~1.6 (PCR) Mb in total.","study_type":"Resequencing","pubmed_ids":[22069447],"external_links":null,"is_released":true,"released_date":"2011-08-25T10:43:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000135","title":"Recurrent somatic DICER1 mutations in non-epithelial ovarian tumors","description":"Background: Germline truncating mutations in DICER1, an RNase III-type endoribonuclease essential for processing of microRNAs, are seen in families with the pleuropulmonary blastoma-family tumor and dysplasia syndrome; these individuals have a propensity to develop non-epithelial ovarian tumors (i.e. sex-cord stromal and germ cell tumors). Methods:  We sequenced the whole transcriptomes or exomes of 14 non-epithelial ovarian tumors and noted closely clustered mutations in the RNase IIIb domain of DICER1 in four cases.  Using Sanger sequencing, we then analyzed additional ovarian tumors for mutations in this region.  The impact of the mutations on the enzymatic activity of Dicer1 was determined using in vitro RNA cleavage assays. Results:  RNase IIIb domain DICER1 mutations were found in 30/102 non-epithelial ovarian tumors (29%), predominantly Sertoli-Leydig cell tumors (26/43, 60%), including 4/4 from individuals with germline DICER1 mutations.  The mutations were restricted to metal binding sites within the RNase IIIb catalytic centres critical for miRNA interaction and cleavage, and were somatic in all 14 cases where germline DNA was available for testing. Of 266 epithelial ovarian and endometrial cancers tested, one case, an ovarian carcinosarcoma, had a hotspot mutation.  In vitro, the mutant DICER proteins showed reduced RNase IIIb activity but retained RNase IIIa activity. Conclusions:  Somatic missense mutations of the RNase IIIb domain of DICER1 are common in non-epithelial ovarian tumors.  Genetic, pathologic, and functional evidence suggest that these mutations do not obliterate DICER1 function, rather, they alter it in specific cell types, a novel mechanism through which perturbed microRNA expression is oncogenic.","abstract":"Background: Germline truncating mutations in DICER1, an RNase III-type endoribonuclease essential for processing of microRNAs, are seen in families with the pleuropulmonary blastoma-family tumor and dysplasia syndrome; these individuals have a propensity to develop non-epithelial ovarian tumors (i.e. sex-cord stromal and germ cell tumors). Methods:  We sequenced the whole transcriptomes or exomes of 14 non-epithelial ovarian tumors and noted closely clustered mutations in the RNase IIIb domain of DICER1 in four cases.  Using Sanger sequencing, we then analyzed additional ovarian tumors for mutations in this region.  The impact of the mutations on the enzymatic activity of Dicer1 was determined using in vitro RNA cleavage assays. Results:  RNase IIIb domain DICER1 mutations were found in 30/102 non-epithelial ovarian tumors (29%), predominantly Sertoli-Leydig cell tumors (26/43, 60%), including 4/4 from individuals with germline DICER1 mutations.  The mutations were restricted to metal binding sites within the RNase IIIb catalytic centres critical for miRNA interaction and cleavage, and were somatic in all 14 cases where germline DNA was available for testing. Of 266 epithelial ovarian and endometrial cancers tested, one case, an ovarian carcinosarcoma, had a hotspot mutation.  In vitro, the mutant DICER proteins showed reduced RNase IIIb activity but retained RNase IIIa activity. Conclusions:  Somatic missense mutations of the RNase IIIb domain of DICER1 are common in non-epithelial ovarian tumors.  Genetic, pathologic, and functional evidence suggest that these mutations do not obliterate DICER1 function, rather, they alter it in specific cell types, a novel mechanism through which perturbed microRNA expression is oncogenic.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-04T16:33:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000136","title":"'Targeted High Throughput Sequencing in Clinical Cancer Settings: Formaldehyde fixed-paraffin embedded (FFPE) tumor tissues, input amount and tumor heterogeneity'","description":"\"Background: Massively parallel sequencing technologies have brought an enormous increase in sequencing throughput. However, these technologies need to be further improved with regard to reproducibility and applicability to clinical samples and settings. Methods: Using identification of genetic variations in prostate cancer as an example we address three crucial challenges in the field of targeted re-sequencing: Small nucleotide variation (SNV) detection in samples of formalin-fixed paraffin embedded (FFPE) tissue material, minimal amount of input sample and sampling in view of tissue heterogeneity.Results: We show that FFPE tissue material can supplement for fresh frozen tissues for the detection of SNVs and that solution-based enrichment experiments can be accomplished with small amounts of DNA with only minimal effects on enrichment uniformity and data variance. Finally, we address the question whether the heterogeneity of a tumor is reflected by different genetic alterations, e.g. different foci of a tumor display different genomic patterns. We show that the tumor heterogeneity plays an important role for the detection of copy number variations, but is of minor importance for the detection of somatic variations.Conclusions: The application of high throughput sequencing technologies in cancer genomics opens up a new dimension for the identification of disease mechanisms. In particular the ability to use small amounts of FFPE samples available from surgical tumor resections and histopathological examinations facilitates the collection of precious tissue materials. However, care needs to be taken in regard to the locations of the biopsies taken, which can have an influence on the prediction of copy number variations. Bearing these technological challenges in mind will significantly improve many large-scale sequencing studies and will - on a long-range - result in a more reliable prediction of individual cancer therapies.\"","abstract":"\"Background: Massively parallel sequencing technologies have brought an enormous increase in sequencing throughput. However, these technologies need to be further improved with regard to reproducibility and applicability to clinical samples and settings. Methods: Using identification of genetic variations in prostate cancer as an example we address three crucial challenges in the field of targeted re-sequencing: Small nucleotide variation (SNV) detection in samples of formalin-fixed paraffin embedded (FFPE) tissue material, minimal amount of input sample and sampling in view of tissue heterogeneity.Results: We show that FFPE tissue material can supplement for fresh frozen tissues for the detection of SNVs and that solution-based enrichment experiments can be accomplished with small amounts of DNA with only minimal effects on enrichment uniformity and data variance. Finally, we address the question whether the heterogeneity of a tumor is reflected by different genetic alterations, e.g. different foci of a tumor display different genomic patterns. We show that the tumor heterogeneity plays an important role for the detection of copy number variations, but is of minor importance for the detection of somatic variations.Conclusions: The application of high throughput sequencing technologies in cancer genomics opens up a new dimension for the identification of disease mechanisms. In particular the ability to use small amounts of FFPE samples available from surgical tumor resections and histopathological examinations facilitates the collection of precious tissue materials. However, care needs to be taken in regard to the locations of the biopsies taken, which can have an influence on the prediction of copy number variations. Bearing these technological challenges in mind will significantly improve many large-scale sequencing studies and will - on a long-range - result in a more reliable prediction of individual cancer therapies.\"","study_type":"Resequencing","pubmed_ids":[21958464],"external_links":null,"is_released":true,"released_date":"2011-09-01T10:58:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000137","title":"ENGAGE___Amendment__500_genes_exon_sequencing_","description":"The ENGAGE project is a FP7 funded EU project aiming to combine genetic and phenotype information from European population based cohorts. In this sub-project we aim to do whole exome sequencing of individuals selected from Health 2000 and FINRISK cohorts. Individuals have been selected based on their metabolic trait phenotypes","abstract":"The ENGAGE project is a FP7 funded EU project aiming to combine genetic and phenotype information from European population based cohorts. In this sub-project we aim to do whole exome sequencing of individuals selected from Health 2000 and FINRISK cohorts. Individuals have been selected based on their metabolic trait phenotypes","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-09-06T10:34:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000138","title":"Radiotherapy_induced_sarcoma","description":"Whole genome library making will be performed on genomic DNA derived from radiotherapy induced sarcoma samples and matched normal DNA from the same patients. Next Generation sequencing will be performed on the resulting libraries and mapped to build 37 of the human reference genome to facilitate the identification of mutations","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina massively parallel sequencing technology, we aim to sequence microRNAs plus the protein coding genome of a number of matched human Chondrosarcoma samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-09-08T18:39:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000139","title":"Splenic_Marginal_Zone_Lymphoma_with_villous_lymphocytes_exome_sequencing","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from ~3 Splenic Marginal Zone Lymphoma with villous lymphocytes samples and matched normal DNA from the same patients. Samples will be multiplexed in one lane of Illumina HiSeq. Sequencing to a coverage of at least 30x will be performed and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina HiSeq massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of matched human disease samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with disease development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-09-08T19:33:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000140","title":"Xenograft_Sequencing","description":"Sequencing of mouse/human carcinoma xenograft samples.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-09-09T09:10:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000141","title":"Herpesvirus_whole_genome_sequencing","description":"This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/This project aims to generate full genome sequences for several members of the human herpesvirus family, including Epstein Barr virus (EBV, HHV4), Kaposi’s sarcoma associated herpesvirus (KSHV, HHV8) and varicella zoster virus (VZV, HHV3). We have designed a new custom pulldown protocol to separate virus DNA from human DNA prior to sequencing and this method will be tested on a range of samples. Virus genome diversity will then be examined by sequencing the virus genome from a large number of different samples.http://www.sanger.ac.uk/resources/downloads/viruses/herpesviridae-lymphocryptovirushttp://www.sanger.ac.uk/resources/downloads/viruses/herpesviridae-rhadinovirushttp://www.sanger.ac.uk/resources/downloads/viruses/herpesviridae-simplexvirus","abstract":"Very little is known about genome diversity of herpesviruses and there are currently very few genome sequences in Genbank. Whole genome sequencing of large DNA viruses is complicated by the difficulty in separating virus DNA from human DNA. In this project we will address this issue by using Agilent SureSelect technology and Illumina deep sequencing to sequence several members of the herpesvirus family, including Epstein Barr virus (EBV, HHV4), Kaposi’s sarcoma associated herpesvirus (KSHV, HHV8) and varicella zoster virus (VZV, HHV3). We have designed custom baits to the available reference sequences and will use these to pull out virus sequence from host DNA and then Illumina sequence the captured virus DNA. The short read data will be assembled into a genome consensus sequence for each virus and importantly, allow analysis of virus minority species, which may be important for pathogenesis.We will use a range of samples including DNA from cell lines latently infected with either EBV or KSHV or both viruses. These data will enable an initial estimation of genome diversity and highlight differences at the genetic level between EBV and KSHV from different cell lines. Further studies will generate herpesvirus genome sequences from clinical samples, including varicella, Kaposi’s sarcoma and nasopharyngeal carcinoma to investigate virus genetic diversity and pathogenic determinants.http://www.sanger.ac.uk/resources/downloads/viruses/herpesviridae-lymphocryptovirushttp://www.sanger.ac.uk/resources/downloads/viruses/herpesviridae-rhadinovirushttp://www.sanger.ac.uk/resources/downloads/viruses/herpesviridae-simplexvirus","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000142","title":"Exome sequencing of patients with structural brain malformations","description":"Exome sequencing of 12 DNA samples obtained from patients with structural brain malformations.","abstract":"Structural brain malformations result from the failure of embryonic developmental processes with abnormalities characteristic of the morphological stage that is disrupted, including failure of neural tube closure and abnormal cell proliferation and/or migration. This study will perform exome sequencing on individuals from at least 5 multiplex families in which causal loci underlying structural brain malformations have previously been mapped. This project will use the Gencode exome design and will sequence each individual to at least 50X mean depth.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-09-20T10:16:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000143","title":"Kuusamo_low_coverage_WGS","description":"The Low coverage Kuusamo whole genome sequencing study will produce whole genome sequencing with 1x coverage on a subset of the Finrisk 2012 sample collection. The sampels in this study have all been collected in Kuusamo.","abstract":"The Low coverage Kuusamo whole genome sequencing study will produce whole genome sequencing with 1x coverage on a subset of the Finrisk 2012 sample collection. The sampels in this study have all been collected in Kuusamo.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001000145","title":"A_study_of_the_genetic_basis_of_evation_by_Acute_Myeloid_Leukaemia_of_Graft_vs_Leukaemia_effects_after_allogeneic_bone_marrow_transplantation","description":"Acute myeloid leukaemia (AML) is an aggressive and molecularly diverse disease with a poor overall survival of 20-25%. With an annual incidence of 2.9 per 100,000, AML is currently the commonest myeloid malignancy in Europe, yet the two main therapeutic options for this disease, anthracyclines and purine analogues, have remained unchanged for over 20 years. Currently patients are stratified at diagnosis according to a series of clinicopathological parameters (e.g. age, white cell count and presence/absence of previous clonal haematological disease) and molecular markers (e.g. chromosomal translocations/deletions, aneuploidy and mutations in genes such as FLT3 and NPM1). Patients with adverse prognostic features, whose prognosis is particularly poor (e.g. &lt;15% long-term survival) are offered treatment with allogeneic bone marrow transplantation (allo-BMT) if a sibling or unrelated donor is available. This can significantly improve survival (e.g. up to 40% long-term survival in some contexts), albeit at the expense of significant toxicity and transplant-related mortality (TRM). Allo-BMT is thought to work in part by allowing the delivery of large doses of chemotherapy followed by haemopoietic \"rescue\" with donor haemopoietic stem cells (haemopoietic failure would otherwise ensue).  However, potentially the most potent effect of allo-BMT is the cytotoxic effect of donor lymphocytes against AML blasts, a phenomenon known as graft-vs-leukaemia (GVL) effect. Increasingly, transplants using reduced chemotherapy intensity (mini-allografts) are being used that partially circumvent the toxicity from chemotherapy and rely on GVL to effect cure. Nevertheless, AML relapse after allo-BMT still occurs at a significant rate of up to 80% depending on the type of transplant. There is accumulating evidence that genetic events in residual leukaemic cells enable them to evade immunodetection and therefore survive the GVL effect and expand to cause relapse. The most striking example of this is the loss of HLA antigens after transplants in which donor and recipient are not fully HLA-matched. In these cases, the leukaemia \"deletes\" the genomic region containing the disparate HLA antigen which was preferentially targeted as \"foreign\" by the GVL effect. However, the genetic basis of immune evasion in the majority of transplants, which are fully HLA matched, is not known. One possibility is that loss of genes coding for antigens outside the HLA locus but which are also targets of GVL may operate, alternatively genetic events that affect processes downstream of immunological cytotoxicity may be responsible.The identification of genetic events that mediate immune evasion would not only facilitate the understanding of this process but can help plan therapeutic interventions that improve the outcomes of allogeneic transplantation for AML and other disorders. We intend to study this by conducting exome sequencing on 6 cases of AMLs from patients that attend my clinic at Addenbrooke's hospital and have relapsed after allogeneic transplantation. Samples from AML diagnosis, remission/normal and AML relapse (total n=18) will be studied to identify somatic mutations in the primary AML and those acquired by the relapsed clone. The 18 samples will also be studied by array CGH to detect regions of genomic amplification or deletion.","abstract":"Acute myeloid leukaemia (AML) is an aggressive and molecularly diverse disease with a poor overall survival of 20-25%. With an annual incidence of 2.9 per 100,000, AML is currently the commonest myeloid malignancy in Europe, yet the two main therapeutic options for this disease, anthracyclines and purine analogues, have remained unchanged for over 20 years. Another treatment option open to some patients with AML is bone marrow transplantation (BMT). This allows eraducation of the disease in some cases and this is thought to be mediated in large part through an immunological attack of the donor immune cells on residual AML cells. However, some AMLs manage to evade this immune attck and relapse some time aftre tyretament. THe nature of this immune-evation  is unknown for most cases, but is very likely to have a genetic basis. For example, in some cases gene loss abrigates the expression of antigenic targets, whilst in other additional genetic mutations may stop immune-mediated apoptosis. This study aims to identify such events, which will in turn improve our understanding of  the mechanisms  of AML relapse after BMT and therefore enable us to improve the outcomes of this type of anti-AML therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-09-21T08:12:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000146","title":"Exome_Sequencing_of_Poor_Prognosis_Acute_Myeloid_Leukaemia","description":"We plan to sequence the exomes of 4 AML cases (tumour and germline) in an effort to discover new mutations in this disease that could improve our understanding of leukaemogenesis and guide the development of new targeted therapies. The Sanger Institute will sequence the exomes of 4 Acute Myeloid Leukaemia cases including tumour and germline DNA so that somatically-acquired, AML-specific mutations can be accurately designated.","abstract":"Acute myeloid leukaemia (AML) is a clonal haematopoietic disorder characterised by proliferation of immature haematopoietic progenitor cells.  Recent next-generation sequencing technologies have revealed a number of novel mutations in this disease that have prognostic impact and illuminate AML pathogenesis.  For example, mutations in genes encoding isocitrate dehydrogenase enzyme isoforms (IDH1 and IDH2) are associated with poor prognosis.  Interestingly, AMLs harbouring IDH2 mutations typically occur in cytogenetically normal cases and do not carry other known AML-associated mutations, implying that novel AML cancer genes remain to be uncovered.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-09-23T10:20:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000147","title":"Osteosarcoma_Whole_Genome","description":"We propose to definitively characterise the somatic genetics of Osteosarcoma cancer through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-09-23T16:09:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000148","title":"Lung_Cancer_Whole_Genomes","description":"We propose to definitively characterise the somatic genetics of Lung cancer through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-09-27T09:41:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000149","title":"Whole-exome sequencing of human pancreatic cancers and characterization of genomic instability caused by MLH1 haploinsufficiency and complete deficiency","description":"Whole-exome sequencing (Exome-Seq) has been successfully applied in several recent studies. We here performed Exome-Seq of 15 pancreatic tumor-normal pairs. We captured 162,073 exons of 16,954 genes and sequenced the targeted regions to a mean coverage of 56 folds. This study identified a total of 1,517 somatic mutations and validated 934 of them by transcriptome sequencing. We detected recurrent mutations in 56 genes. Among them, 41 have not been described. The mutation rates varied widely among tumors. The diversity of mutation rates was significantly correlated with the distinct MLH1 copy-number status. Exome-Seq revealed intensive genomic instability in a tumor with MLH1 homozygous deletion, indicated by a dramatically elevated mutation rate of somatic substitutions, small insertions/deletions (indels), as well as indels presented at microsatellites. Notably, we detected MLH1 allelic loss in 4 tumors. MLH1 expression was decreased by nearly half in these cases. While they were negative in the conventional microsatellite instability assay, they showed a 10.5-fold increase in the mutation rate of somatic indels, e.g. truncating indels in TP53 and TGFBR2, indicating MLH1 haploinsufficiency in correction of DNA indel errors. We further analyzed the exomes of 15 renal cell carcinomas (RCCs) and confirmed MLH1 haploinsufficiency. We observed a significant increase in the mutation rate of somatic indels in affected cases and identified recurrent truncating indels in several cancer genes such as VHL, PBRM1 and JARID1C. Together, our data suggest that MLH1 hemizygous deletion, through increasing the mutation rate of somatic indels, could drive the development and progression of sporadic cancers.","abstract":"Whole-exome sequencing (Exome-Seq) has been successfully applied in several recent studies. We here performed Exome-Seq of 15 pancreatic tumor-normal pairs. We captured 162,073 exons of 16,954 genes and sequenced the targeted regions to a mean coverage of 56 folds. This study identified a total of 1,517 somatic mutations and validated 934 of them by transcriptome sequencing. We detected recurrent mutations in 56 genes. Among them, 41 have not been described. The mutation rates varied widely among tumors. The diversity of mutation rates was significantly correlated with the distinct MLH1 copy-number status. Exome-Seq revealed intensive genomic instability in a tumor with MLH1 homozygous deletion, indicated by a dramatically elevated mutation rate of somatic substitutions, small insertions/deletions (indels), as well as indels presented at microsatellites. Notably, we detected MLH1 allelic loss in 4 tumors. MLH1 expression was decreased by nearly half in these cases. While they were negative in the conventional microsatellite instability assay, they showed a 10.5-fold increase in the mutation rate of somatic indels, e.g. truncating indels in TP53 and TGFBR2, indicating MLH1 haploinsufficiency in correction of DNA indel errors. We further analyzed the exomes of 15 renal cell carcinomas (RCCs) and confirmed MLH1 haploinsufficiency. We observed a significant increase in the mutation rate of somatic indels in affected cases and identified recurrent truncating indels in several cancer genes such as VHL, PBRM1 and JARID1C. Together, our data suggest that MLH1 hemizygous deletion, through increasing the mutation rate of somatic indels, could drive the development and progression of sporadic cancers.","study_type":"Exome Sequencing","pubmed_ids":[22156295],"external_links":null,"is_released":true,"released_date":"2011-09-30T13:41:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000150","title":"Whole-exome sequencing of human pancreatic cancers and characterization of genomic instability caused by MLH1 haploinsufficiency and complete deficiency","description":"Whole-exome sequencing (Exome-Seq) has been successfully applied in several recent studies. We here sequenced the exomes of 15 pancreatic tumor cell lines and their matched normal samples. We captured 162,073 exons of 16,954 genes and sequenced the targeted regions to a mean coverage of 56-fold. This study identified a total of 1,517 somatic mutations and validated 934 mutations by transcriptome sequencing. We detected recurrent mutations in 56 genes. Among them, 41 have not been described. The mutation rates varied widely among cell lines. The diversity of mutation rates was significantly correlated with the distinct MLH1 copy-number status. Exome-Seq revealed intensive genomic instability in a cell line with MLH1 homozygous deletion, indicated by a dramatically elevated rate of somatic substitutions, small insertions/deletions (indels), as well as indels in microsatellites. Notably, we found that MLH1 expression was decreased by nearly half in cell lines with allelic loss of MLH1. While these cell lines were negative in conventional microsatellite instability assay, they showed a 10.5-fold increase in the rate of somatic indels, e.g. truncating indels in TP53 and TGFBR2, indicating MLH1 haploinsufficiency in correction of DNA indel errors. We further analyzed the exomes of 15 renal cell carcinomas and confirmed MLH1 haploinsufficiency. We observed a much higher rate of indel mutations in affected cases and identified recurrent truncating indels in several cancer genes such as VHL, PBRM1 and JARID1C. Together, our data suggest that MLH1 hemizygous deletion, through increasing the rate of indel mutations, could drive the development and progression of sporadic cancers.","abstract":"Whole-exome sequencing (Exome-Seq) has been successfully applied in several recent studies. We here sequenced the exomes of 15 pancreatic tumor cell lines and their matched normal samples. We captured 162,073 exons of 16,954 genes and sequenced the targeted regions to a mean coverage of 56-fold. This study identified a total of 1,517 somatic mutations and validated 934 mutations by transcriptome sequencing. We detected recurrent mutations in 56 genes. Among them, 41 have not been described. The mutation rates varied widely among cell lines. The diversity of mutation rates was significantly correlated with the distinct MLH1 copy-number status. Exome-Seq revealed intensive genomic instability in a cell line with MLH1 homozygous deletion, indicated by a dramatically elevated rate of somatic substitutions, small insertions/deletions (indels), as well as indels in microsatellites. Notably, we found that MLH1 expression was decreased by nearly half in cell lines with allelic loss of MLH1. While these cell lines were negative in conventional microsatellite instability assay, they showed a 10.5-fold increase in the rate of somatic indels, e.g. truncating indels in TP53 and TGFBR2, indicating MLH1 haploinsufficiency in correction of DNA indel errors. We further analyzed the exomes of 15 renal cell carcinomas and confirmed MLH1 haploinsufficiency. We observed a much higher rate of indel mutations in affected cases and identified recurrent truncating indels in several cancer genes such as VHL, PBRM1 and JARID1C. Together, our data suggest that MLH1 hemizygous deletion, through increasing the rate of indel mutations, could drive the development and progression of sporadic cancers.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000151","title":"Exome_sequencing_Parkinson_s_disease_patients","description":"In this project we will sequence the exomes of 250 patients with Parkinson's disease","abstract":"Degenerative disorders of the brain, including PD, are becoming more common as the population gets older. The symptoms of PD include tremor, stiffness, and slowness of movement while non-motor symptoms include memory loss, sleep problems, low mood, anxiety, and constipation. PD involves the loss of neurons that produce the chemical dopamine referred to as dopaminergic neurons. Various other brain areas are also affected throughout the course of the illness. Our understanding of what causes PD is limited and there is currently no cure or treatment that can prevent or reverse the neuronal cell loss seen in PD. Treatment is made more difficult because the physical symptoms of the disease only become apparent when the underlying neuronal changes are well underway. Research must make every attempt to identify early changes, before the symptoms become apparent. Detection of this pre-symptomatic phase of PD using biomarkers will identify those individuals most likely to benefit from future neuroprotective therapies. It is becoming clear that genetic variation is an important factor in susceptibility to PD and many Parkinson's loci remain to be discovered. In this project we will undertake exome resequencing in 250 Parkinson's patients collected as part of the Oxford Parkinson's Disease Centre Discovery cohort. All patients have undergone a very detailed clinical examination to allow sequence variants to be associated with detailed subphenotype","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-09-30T16:09:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000152","title":"Full genome sequencing of a monozygotic twin discordant for schizophrenia","description":"We sequenced the genomes from a monozygotic twin discordant for schizophrenia and a tumor-normal pair of an ovarian cancer patient. Using whole-genome twin data to discriminate between correctly identified single nucleotide variants (SNVs) and errors a strategy for the accurate detection of SNVs was developed. By applying stringent sequencing quality measures, excluding error-prone regions and selecting SNVs identified by different mapping and variation calling algorithms, error rates were ~37-fold reduced. This enabled us to identify the first discordant SNVs in monozygotic twins using whole-genome sequencing. In addition, by showing that novel SNVs are highly enriched in errors, accurate estimates of the number of novel and rare SNVs occurring in unrelated Caucasian individuals were obtained. Finally, somatic mutations in coding and regulatory sequences were reliably identified in the highly rearranged ovarian tumor. Overall, our data demonstrate that strategies to reduce error rates in whole-genomes are required for disease gene discovery.","abstract":"We sequenced the genomes from a monozygotic twin discordant for schizophrenia and a tumor-normal pair of an ovarian cancer patient. Using whole-genome twin data to discriminate between correctly identified single nucleotide variants (SNVs) and errors a strategy for the accurate detection of SNVs was developed. By applying stringent sequencing quality measures, excluding error-prone regions and selecting SNVs identified by different mapping and variation calling algorithms, error rates were ~37-fold reduced. This enabled us to identify the first discordant SNVs in monozygotic twins using whole-genome sequencing. In addition, by showing that novel SNVs are highly enriched in errors, accurate estimates of the number of novel and rare SNVs occurring in unrelated Caucasian individuals were obtained. Finally, somatic mutations in coding and regulatory sequences were reliably identified in the highly rearranged ovarian tumor. Overall, our data demonstrate that strategies to reduce error rates in whole-genomes are required for disease gene discovery.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-10-03T15:15:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000153","title":"Exome Sequencing of Gastric Cancer","description":"GASTRIC cancer (GC) is a heterogeneous disease with multiple environmental etiologies and alternative pathways of carcinogenesis. Beyond mutations in TP53, alterations in other genes or pathways account only for small subsets of the disease. We performed exome sequencing of 22 GCs and identified mutated genes and pathway alterations previously unreported: genes involved in chromatin modification were commonly mutated. A downstream validation study confirmed frequent inactivating mutations and/or protein deficiency of the SWI/SNF chromatin remodeling complex gene ARID1A in 83% of GCs with microsatellite instability, 73% of GCs with Epstein-Barr virus (EBV) infection, and 11% of non-EBV microsatellite stable GCs. The mutation spectrum of ARID1A differs between molecular subtypes and the mutation prevalence is negatively associated with mutations in TP53. Clinically, ARID1A alterations were associated with better prognosis in a stage-independent manner. These results revealed the genomic landscape and highlighted the importance of chromatin remodeling in the molecular taxonomy of GCs.","abstract":"GASTRIC cancer (GC) is a heterogeneous disease with multiple environmental etiologies and alternative pathways of carcinogenesis. Beyond mutations in TP53, alterations in other genes or pathways account only for small subsets of the disease. We performed exome sequencing of 22 GCs and identified mutated genes and pathway alterations previously unreported: genes involved in chromatin modification were commonly mutated. A downstream validation study confirmed frequent inactivating mutations and/or protein deficiency of the SWI/SNF chromatin remodeling complex gene ARID1A in 83% of GCs with microsatellite instability, 73% of GCs with Epstein-Barr virus (EBV) infection, and 11% of non-EBV microsatellite stable GCs. The mutation spectrum of ARID1A differs between molecular subtypes and the mutation prevalence is negatively associated with mutations in TP53. Clinically, ARID1A alterations were associated with better prognosis in a stage-independent manner. These results revealed the genomic landscape and highlighted the importance of chromatin remodeling in the molecular taxonomy of GCs.","study_type":"Exome Sequencing","pubmed_ids":[22037554],"external_links":null,"is_released":true,"released_date":"2011-10-04T11:15:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000154","title":"Genome Landscape of Primary Pancreatic Ductal Adenocarcinoma","description":"The purpose of the Australian ICGC Pancreatic Cancer Genome Sequencing Initiativestudy is to identify the common driving mutations underlying the initiation anddevelopment of Pancreatic Adenocarcinoma in a large cohort of pancreatic cancerpatients (n=350). Matched genome sequences will be generated from normal tissue(duodenum) and resected primary tumour tissue in each patient using exome andwhole genome sequencing. The complete repertoire of somatic mutations will bedetermined (substitutions, indels, copy number changes and structural changes).Where possible, matched transcriptome sequencing will also be carried out todetermine locus activity, which mutations are actively expressed and whichrearrangements give rise to gene-fusion transcripts.","abstract":"The purpose of the Australian ICGC Pancreatic Cancer Genome Sequencing Initiativestudy is to identify the common driving mutations underlying the initiation anddevelopment of Pancreatic Adenocarcinoma in a large cohort of pancreatic cancerpatients (n=350). Matched genome sequences will be generated from normal tissue(duodenum) and resected primary tumour tissue in each patient using exome andwhole genome sequencing. The complete repertoire of somatic mutations will bedetermined (substitutions, indels, copy number changes and structural changes).Where possible, matched transcriptome sequencing will also be carried out todetermine locus activity, which mutations are actively expressed and whichrearrangements give rise to gene-fusion transcripts.","study_type":"Other","pubmed_ids":[23103869,26909576],"external_links":null,"is_released":true,"released_date":"2011-10-07T14:38:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000155","title":"Matched_Ovarian_Cancer_Sequencing","description":"Genomic libraries (500 bps) will be generated from  total genomic DNA derived from 15 ovarian cancer samples and subjected to total of eight lanes of 37 bp, paired end sequencing on the llumina GA. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemias, lymphomas and soft tissue tumors. However, conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution, thus the role of genomic rearrangement in human ovarian cancer is unknown. We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting ovarian cancer genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-10-13T18:04:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000156","title":"Otosclerosis_gene_discovery_","description":"DNA from patients with otosclerosis will be subjected to exome sequencing","abstract":"Otosclerosis is an osseous dyscrasia affecting structures derived from the otic capsule often leading to stapes fixation and conductive hearing loss and also in some cases a sensorineural hearing loss.  The hereditary nature of this disease has been recognised for over a century but the precise genetic basis remains undefined.  Ten genomic loci have been linked to otosclerosis using linkage analysis but in each case no causal gene has been identified. Heterogeneity means analysis has to be restricted to extended single pedigrees which due to adult onset are rare, therefore the power of linkage is reduced.  DNA from ten patients from a cohort of otosclerosis patients will be used for genetic analysis by exome sequencing to identify good candidate mutations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-10-19T14:38:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000157","title":"Hearing_loss_in_adults_from_South_Carolina_","description":"DNA  from ten individuals from South Carolina with progressive hearing loss will be subjected to exome sequencing","abstract":"Age-related hearing loss is a common disorder with a significant heritability around 50%, but the genetic architecture is not well understood.  It is likely to be highly genetically heterogeneous, similar in this respect to childhood deafness, and a number of single gene mutations associated with late-onset progressive hearing loss have been identified in rare large families segregating deafness.  This project aims to use exome sequencing to ask if single gene mutations can be identified as likely causes of the hearing loss.  Ten individuals with well-characterised progressive hearing loss will be subjected to exome sequencing and the sequence will be analysed to detect evidence for pathogenic mutations in known deafness genes before looking for new genes underlying the hearing loss.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-10-19T15:54:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000158","title":"Complete Genomics paired end sequencing; Ovarian cancer","description":"We sequenced the genomes from a monozygotic twin discordant for schizophrenia and a tumor-normal pair of an ovarian cancer patient. Using whole-genome twin data to discriminate between correctly identified single nucleotide variants (SNVs) and errors a strategy for the accurate detection of SNVs was developed. By applying stringent sequencing quality measures, excluding error-prone regions and selecting SNVs identified by different mapping and variation calling algorithms, error rates were ~37-fold reduced. This enabled us to identify the first discordant SNVs in monozygotic twins using whole-genome sequencing. In addition, by showing that novel SNVs are highly enriched in errors, accurate estimates of the number of novel and rare SNVs occurring in unrelated Caucasian individuals were obtained. Finally, somatic mutations in coding and regulatory sequences were reliably identified in the highly rearranged ovarian tumor. Overall, our data demonstrate that strategies to reduce error rates in whole-genomes are required for disease gene discovery.","abstract":"We sequenced the genomes from a monozygotic twin discordant for schizophrenia and a tumor-normal pair of an ovarian cancer patient. Using whole-genome twin data to discriminate between correctly identified single nucleotide variants (SNVs) and errors a strategy for the accurate detection of SNVs was developed. By applying stringent sequencing quality measures, excluding error-prone regions and selecting SNVs identified by different mapping and variation calling algorithms, error rates were ~37-fold reduced. This enabled us to identify the first discordant SNVs in monozygotic twins using whole-genome sequencing. In addition, by showing that novel SNVs are highly enriched in errors, accurate estimates of the number of novel and rare SNVs occurring in unrelated Caucasian individuals were obtained. Finally, somatic mutations in coding and regulatory sequences were reliably identified in the highly rearranged ovarian tumor. Overall, our data demonstrate that strategies to reduce error rates in whole-genomes are required for disease gene discovery.","study_type":"Whole Genome Sequencing","pubmed_ids":[25085081],"external_links":null,"is_released":true,"released_date":"2011-10-20T15:17:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000159","title":"Exome sequencing of patients with rare neurological disorders","description":"Exome sequencing of patients and their families with diverse rare neurological disorders. Some families have prior linkage data identifying a specific chromosomal interval or interest, other families do not have linkage data available. Many of these families come from special populations whose demography or preference for consanguineous marriages make them particularly tractable for genetic studies.","abstract":"Exome sequencing of patients and their families with diverse rare neurological disorders. Some families have prior linkage data identifying a specific chromosomal interval or interest, other families do not have linkage data available. Many of these families come from special populations whose demography or preference for consanguineous marriages make them particularly tractable for genetic studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-10-25T13:35:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000160","title":"Matched_Pair_Cancer_Cell_line_Whole_Genomes","description":"We propose to definitively characterise the somatic genetics of 29 matched pair cell lines through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-10-25T15:24:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000161","title":"Triple_Negative_Breast_Cancer_sequencing","description":"We propose to definitively characterise the somatic genetics of triple-ve breast cancer through generation of comprehensive catalogues of somatic mutations in a number of cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-10-27T12:10:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000162","title":"Genetic_background_for_the_major_psychiatric_disorders_in_the_general_Finnish_population","description":"Low coverage (4-6x) sequencing on samples from population cohorts (Finrisk, Health2000) will be done at Wellcome Trust Sanger Institute (WTSI) using Illumina HiSeq sequencing technology. We will produce 100bp paired end reads. Variants will be called using the 1000 Genomes Project pipeline.  The samples have been selected from a national representative set of 8028 samples from persons of 30 years or older, which were screened for psychotic and bipolar disorders using the Composite International Diagnostic Interview, self-reported diagnoses, medical examination, and national registers.","abstract":"Low coverage (4-6x) sequencing on samples from population cohorts (Finrisk, Health2000) will be done at Wellcome Trust Sanger Institute (WTSI) using Illumina HiSeq sequencing technology. We will produce 100bp paired end reads. Variants will be called using the 1000 Genomes Project pipeline.  The samples have been selected from a national representative set of 8028 samples from persons of 30 years or older, which were screened for psychotic and bipolar disorders using the Composite International Diagnostic Interview, self-reported diagnoses, medical examination, and national registers.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-02T11:23:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000163","title":"Osteosarcoma_Exome_Sequencing","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 50 osteosarcoma cancers and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 100 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina GA massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of 50 matched human osteosarcoma samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with osteosarcoma development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-02T11:28:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000164","title":"ESGI___Molecular_diagnosis_for_mitochondrial_disorders_","description":"The MITOEXME project aims to improve protocols for molecular diagnosis of patients with OXPHOS disorders with a focus on a next generation sequencing methods and to increase the knowledge of pahtophysiological mechanisms by identification of new targets and cellular studies. In this project we will sequence the exomes fo 120 patients.","abstract":"The MITOEXME project aims to improve protocols for molecular diagnosis of patients with OXPHOS disorders with a focus on a next generation sequencing methods and to increase the knowledge of pahtophysiological mechanisms by identification of new targets and cellular studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-04T09:49:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000165","title":"Monotherapy_Breast_Cancer","description":"These samples are from locally advanced breast cancers that have been treated with epirubicin monotherapy before surgery. We will sequence some samples from patients with good response to the therapy and some with poor response to the therapy.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-14T11:02:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000166","title":"Breast_Cancer_Matched_Pair_Cell_Line_Whole_Genomes","description":"We propose to definitively characterise the somatic genetics of matched pair breast cancer cell lines through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-14T11:17:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000167","title":"Abnormal_foetal_development_exome_trios","description":"This project is to explore the contribution of de novo mutations to severe structural malformations diagnosed prenatally using ultrasound. These malformations include heart, CNS, renal and GI abnormalities. In this pilot project we aim to exome sequence 30 parent-foetus trios to ~50X mean coverage and identify de novo functional variants using an algorithm developed in the Hurles group","abstract":"This project is to explore the contribution of de novo mutations to severe structural malformations diagnosed prenatally using ultrasound. These malformations include heart, CNS, renal and GI abnormalities. In this pilot project we aim to exome sequence 30 parent-foetus trios to ~50X mean coverage and identify de novo functional variants using an algorithm developed in the Hurles group","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-15T18:43:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000168","title":"Whole_exome_studies_in_inherited_muscle_disorders","description":"Complete exome sequence data were generated on 11 patients suffering from congenital muscular dystrophy, along with one unaffected individual. The patients consist of nine unaffected individuals and two half-sisters; the unaffected individual is the mother of the two half-sisters. Further clinical details are available upon request. Exome sequence was captured using [xxx] arrays and sequenced on Illumina HiSeq with paired-end 75 bp reads.","abstract":"Complete exome sequence data were generated on 11 patients suffering from congenital muscular dystrophy, along with one unaffected individual. The patients consist of nine unaffected individuals and two half-sisters; the unaffected individual is the mother of the two half-sisters. Further clinical details are available upon request. Exome sequence was captured using [xxx] arrays and sequenced on Illumina HiSeq with paired-end 75 bp reads.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000169","title":"Whole genome sequencing of matched primary and metastatic acral melanomas","description":"Next generation sequencing has enabled systematic discovery of mutational spectra in cancer samples. Here we used whole genome sequencing to characterise somatic mutations and structural variation in a primary acral melanoma and its lymph node metastasis. Our data show that the somatic mutational rates in this acral melanoma sample pair was more comparable to the rate reported in cancer genomes not associated with mutagenic exposure than in the genome of a melanoma cell line or the transcriptome of melanoma short-term cultures. Despite the perception that acral skin is sun-protected, the dominant mutational signature in these samples is compatible with damage due to ultraviolet light exposure. A nonsense mutation in ERCC5 discovered in both the primary and metastatic tumours, could also have contributed to the mutational signature through accumulation of unrepaired dipyrimidine lesions. However, evidence of transcription-coupled repair was suggested by the lower mutational rate in the transcribed regions and expressed genes. The primary and the metastasis are highly similar at the level of global gene copy number alterations, loss of heterozygosity and single nucleotide variation (SNV). Furthermore, the majority of the SNVs in the primary tumour were propagated in the metastasis and one non-synonymous coding SNV and one splice site mutation appeared to arise de novo in the metastatic lesion.","abstract":"Next generation sequencing has enabled systematic discovery of mutational spectra in cancer samples. Here we used whole genome sequencing to characterise somatic mutations and structural variation in a primary acral melanoma and its lymph node metastasis. Our data show that the somatic mutational rates in this acral melanoma sample pair was more comparable to the rate reported in cancer genomes not associated with mutagenic exposure than in the genome of a melanoma cell line or the transcriptome of melanoma short-term cultures. Despite the perception that acral skin is sun-protected, the dominant mutational signature in these samples is compatible with damage due to ultraviolet light exposure. A nonsense mutation in ERCC5 discovered in both the primary and metastatic tumours, could also have contributed to the mutational signature through accumulation of unrepaired dipyrimidine lesions. However, evidence of transcription-coupled repair was suggested by the lower mutational rate in the transcribed regions and expressed genes. The primary and the metastasis are highly similar at the level of global gene copy number alterations, loss of heterozygosity and single nucleotide variation (SNV). Furthermore, the majority of the SNVs in the primary tumour were propagated in the metastasis and one non-synonymous coding SNV and one splice site mutation appeared to arise de novo in the metastatic lesion.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-29T09:45:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000170","title":"20_Matched_Pair_Breast_Cancer_Genomes","description":"We propose to definitively characterise the somatic genetics of 20 breast cancers through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing coupled with integrated transcriptomic data.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-29T10:15:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000171","title":"Exome_sequencing_of_blastic_plasmacytoid_dendritic_cell_neoplasms","description":"Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive haematological malignancy derived from precursors of plasmacytoid dendritic cells. Due to the rarity of BPDCNs our knowledge of their molecular pathogenesis was until recently confined to observations describing reccurent chromosomal deletions involving chromosomes 5q, 12p, 13q, 6q, 15q and 9. A recent publication went on to delineate the common deleted regions using aCGH and demonstrated that these centred around known tumour suppressor genes including CDKN2A/B (9p21.3), RB1 (12p13.2-14.3), CDKN1B (13q11-q12) and IKZF1 (7p12.2).These mutations are found recurrently in several different cancers and in most cases are thought to be involved in tumour progression rather than initiation. However, the well-defined nature and cellular ontogeny of these neoplasms suggests strongly that they share one or a few characteristic mutations as has been demonstrated for other uncommon but well-defined neoplasms such as Hairy Cell Leukemia (BRAF) and ovarian Granulosa Cell tumours (FOXL2).","abstract":"We will perform whole exome sequencing in matched tumour-normal pairs from 6 patients in order to isolate causative mutations. We have access to another 6 samples (without matched normal) to validate our findings by targeted re-sequencing","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-30T12:57:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000172","title":"BRAF_and_MEK_resistant_cell_line_clones","description":"The Sanger Institute has the largest collection of genetically-characterised cancer cell lines world-wide (we have collected &gt;1000 human cancer cell lines which are being screened against &gt;400 cancer therapeutics (http://www.sanger.ac.uk/genetics/CGP/translation). These lines have been characterized to the level of gene copy number, gene expression and cancer gene mutation sequence data. This has enabled us to select melanoma lines with varying BRAF mutational status and that show sensitivity to a range of BRAF inhibitors. Sensitive lines are being used to generate resistant clones by serial exposure to increasing concentrations of BRAF and MEK inhibitors and these are being characterised by genome-wide copy number analysis as well as by whole exome sequencing.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-30T16:08:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000173","title":"Testing_the_feasibility_of_genome_scale_sequencing_in_routinely_collected_FFPE_cancer_specimens_versus_matched_fresh_frozen_samples","description":"Testing the feasibility of genome-scale sequencing in routinely collected formalin-fixed paraffin-embedded (FFPE) cancer specimens versus matched fresh-frozen samples using whole exome and targeted exome capture prior to Illumina sequencing.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale. Being able to follow up studies ina larger cohort from FFPE samples would greatly increase the capacity of these studies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-30T16:13:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000174","title":"Balanced_Ependymoma","description":"We propose to definitively characterise the somatic genetics of a number of pediatric malignant tumours including ependymoma, high grade glioma and central nervous system primitive neurectodermal tumours through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-30T16:34:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000175","title":"PMF_Exome_Study","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 50 Primary Myelofibrosis Myeloproliferative Disease  samples and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 100 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina GA massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of 50 matched human Primary Myelofibrosis Myeloproliferative disease samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with Myeloproliferative disease development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-30T16:35:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000176","title":"FRCC_Exome_sequencing","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from FRCC patients. one lane of Illumina Hiseq sequencing will be performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina GA massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of 50 matched human Adenoid cystic carcinoma samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with Adenoid cystic carcinoma development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-30T16:43:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000177","title":"Meningioma_Exome","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from Meningioma tumour samples and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting exome libraries and mapped build 37 of the human reference genome to facilitate the identification of novel cancer genes.","abstract":"Cancer is driven by mutation. Illumina GA massively parallel sequencing technology will be applied to Agilent exome hybridisation capture libraries and total genomic paired-end libraries. Bespoke algorithms are being developed to identify the somatically acquired structural variants, point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with Meningioma development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-30T16:44:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000178","title":"Cell_Line_Sub_Clone_Rearrangement_Screen","description":"Genomic libraries (500 bps) will be generated from total genomic DNA cancer samples and subjected to paired end sequencing on the llumina GA. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemias, lymphomas and soft tissue tumors. However, conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution, thus the role of genomic rearrangement in common epithelial cancer is unknown. We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting common epithelial cancer genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-30T16:45:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000179","title":"Renal_Matched_Pair_Cell_Line_Exome_Sequencing","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from renal cancer cell lines and matched normal DNA from the same patient. Illumina GA sequencing will be performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina GA massively parallel sequencing technology, we aim to sequence the microRNAs plus the protein coding genome of matched human renal cancer cell line samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with renal cancer development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-30T16:46:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000180","title":"Mixed_Leukemia_Rearrangement_Screen","description":"Genomic libraries will be generated from total genomic DNA derived from Mixed Leukemia and MPD samples and subjected to total of eight lanes of 37 bp, paired end sequencing on the illumina GA. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemia, lymphomas and soft tissue tumors. However, conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution, thus the role of genomic rearrangement in human adenoid cystic carcinoma is unknown. We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting leukemia genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-30T16:48:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000181","title":"Chondrosarcoma_Validation_Study","description":"Agilent whole exome hybridisation capture was performed on genomic DNA derived from Chondrosarcoma cancer and matched normal DNA from the same patients. Next Generation sequencing performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes. Now we aim to re find and validate the findings of those exome libraries using bespoke pulldown methods and sequencing the products.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-11-30T17:25:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000182","title":"Signatures of mismatch repair deficiency in cancer genomes","description":"DNA replication errors occurring in mismatch repair (MMR) deficient cells persist as mismatch mutations and predispose to a range of tumors. Here, we sequenced the first whole-genomes from MMR-deficient tumors and observed that mutation rates were drastically increased relative to MMR-proficient endometrial tumors.","abstract":"DNA replication errors occurring in mismatch repair (MMR) deficient cells persist as mismatch mutations and predispose to a range of tumors. Here, we sequenced the first whole-genomes from MMR-deficient tumors and observed that mutation rates were drastically increased relative to MMR-proficient endometrial tumors.","study_type":"Whole Genome Sequencing","pubmed_ids":[25085081],"external_links":null,"is_released":true,"released_date":"2011-12-05T10:44:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000183","title":"TraDIS_R_D_optimisation","description":"Aim is to improve results gained from eukaryotic transposon integration site sequencing using illumina platform.","abstract":"A problem with TraDIS libraries is the significant amount of non-specific product that is produced during PCR amplification.  We will use biotinylated 1st round primers to enrich for transposon-containing fragments.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000184","title":"Exome_sequencing_of_Congenital_Heart_Disease_families_Hannover","description":"This project aims to study at least 60 exomes from families with congenital heart disease (CHD). The samples have been selected in  Hannover, Germany in collaboration with Harald Bertram.  Ethic approval has been sought for in Hannover, Germany and a HDMMC agreement for submitting these samples is in place at the WTSI. The phenotype we wil primarily focus our analysis is severe Left Ventricular Outflow Tract Obstructions (LVOTO) and additional other familiar cases with CHD. The indexed  Agilent whole exome pulldown libraries will be sequenced on 75bp PE HiSeq (Illumina).","abstract":"This project aims to study at least 60 exomes from families with congenital heart disease (CHD). The samples have been selected in  Hannover, Germany in collaboration with Harald Bertram.  Ethic approval has been sought for in Hannover, Germany and a HDMMC agreement for submitting these samples is in place at the WTSI. The phenotype we wil primarily focus our analysis is severe Left Ventricular Outflow Tract Obstructions (LVOTO) and additional other familiar cases with CHD. The indexed  Agilent whole exome pulldown libraries will be sequenced on 75bp PE HiSeq (Illumina).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000185","title":"Exome_sequencing_of_Congenital_Heart_Disease_families_Leuven","description":"This project aims to study at least 90 exomes from families with congenital heart disease. The samples have been selected in Leuven in collaboration with Koen Devriendt.  Ethic approval has been sought for in Leuven, Belgium and a HDMMC agreement for submitting these samples is in place at the WTSI. The phenotype we wil primarily focus our analysis is severe Left Ventricular Outflow Tract Obstructions (LVOTO) and Atrioventricular Septal Defect (AVSD). The indexed  Agilent whole exome pulldown libraries will be sequenced on 75bp PE HiSeq (Illumina).","abstract":"This project aims to study at least 90 exomes from families with congenital heart disease. The samples have been selected in Leuven in collaboration with Koen Devriendt.  Ethic approval has been sought for in Leuven, Belgium and a HDMMC agreement for submitting these samples is in place at the WTSI. The phenotype we wil primarily focus our analysis is severe Left Ventricular Outflow Tract Obstructions (LVOTO) and Atrioventricular Septal Defect (AVSD). The indexed  Agilent whole exome pulldown libraries will be sequenced on 75bp PE HiSeq (Illumina).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-12-09T09:14:18+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000186","title":"Exome_sequencing_of_Congenital_Heart_Disease_families_Montreal","description":"This project aims to study at least 60 exomes from families with congenital heart disease. The samples have been selected in Montreal in collaboration with Dr. Gregor Andelfinger.  Local ethic approval has been sought for in Montreal, Canada and a HDMMC/MTA agreement for submitting these samples is in place at the WTSI. The phenotype we wil primarily focus our analysis is severe Left Ventricular Outflow Tract Obstructions (LVOTO). The indexed Agilent whole exome pulldown libraries will be sequenced on 75bp PE HiSeq (Illumina)","abstract":"This project aims to study at least 60 exomes from families with congenital heart disease. The samples have been selected in Montreal in collaboration with Dr. Gregor Andelfinger.  Local ethic approval has been sought for in Montreal, Canada and a HDMMC/MTA agreement for submitting these samples is in place at the WTSI. The phenotype we wil primarily focus our analysis is severe Left Ventricular Outflow Tract Obstructions (LVOTO). The indexed Agilent whole exome pulldown libraries will be sequenced on 75bp PE HiSeq (Illumina)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000187","title":"Exome_sequencing_of_Congenital_Heart_Disease_families_Royal_Brompton","description":"This project aims to study at least 90 exomes from families with congenital heart disease. The samples have been selected at the Royal, Brompton Hospital in collaboration with Stuart Cook and Piers Daubeney.  Ethic approval has been sought for in the UK and a HDMMC agreement for submitting these samples is in place at the WTSI. The phenotype we wil primarily focus our analysis is severe Left Ventricular Outflow Tract Obstructions (LVOTO) and Atrioventricular Septal Defect (AVSD). The indexed  Agilent whole exome pulldown libraries will be sequenced on 75bp PE HiSeq (Illumina).","abstract":"This project aims to study at least 90 exomes from families with congenital heart disease. The samples have been selected at the Royal, Brompton Hospital in collaboration with Stuart Cook and Piers Daubeney.  Ethic approval has been sought for in the UK and a HDMMC agreement for submitting these samples is in place at the WTSI. The phenotype we wil primarily focus our analysis is severe Left Ventricular Outflow Tract Obstructions (LVOTO) and Atrioventricular Septal Defect (AVSD). The indexed  Agilent whole exome pulldown libraries will be sequenced on 75bp PE HiSeq (Illumina).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-12-09T09:26:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000188","title":"Chordoma_Exome_Sequencing","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from Chordoma cancers and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina GA massively parallel sequencing technology, we aim to sequence microRNAs plus the protein coding genome of matched human Chordoma samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with Chordoma development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-12-14T13:59:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000189","title":"Dyslipidemia","description":"These samples include exome sequences of family members with dyslipidemias from Finnish origin.","abstract":"These samples include exome sequences of family members with dyslipidemias from Finnish origin.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-12-19T13:23:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000190","title":"Paroxysmal_Neurological_Disorders_2","description":"We are sequencing the exomes of patients with paroxysmal neurological disorders mainly focusing on migraine and epilepsy. Cases are collected from performance sites of members of the International Headache Genetics consortium and EuroEPINOMICS. Most cases have a strong family history. The study sample will include both cases and controls.","abstract":"We are sequencing the exomes of patients with paroxysmal neurological disorders mainly focusing on migraine and epilepsy. Cases are collected from performance sites of members of the International Headache Genetics consortium and EuroEPINOMICS. Most cases have a strong family history. The study sample will include both cases and controls.","study_type":"Other","pubmed_ids":[25262651],"external_links":null,"is_released":true,"released_date":"2012-01-03T15:48:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000191","title":"CML_blast_phase_rearrangement_screen","description":"Genomic libraries (500 bps) will be generated from total genomic DNA derived from 10 Chronic Myeloid Leukemia in blast phase samples and subjected to a total of two lanes of 50 bp, paired end sequencing on the llumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions","abstract":"Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. In hematological malignancies the majority of known human cancer genes are somatically rearranged. Conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution. We aim to use massively parallel paired end sequencing to characterise the occurrence of critical genomic rearrangements for a selected sample set of Chronic Myeloid Leukemia samples in blast phase, understand the clonal evolution of those and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2011-08-26T12:17:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000192","title":"Somatic Histone H3 Mutations in Diffuse Intrinsic Pontine Gliomas and Non-Brainstem Paediatric Glioblastomas","description":"To identify somatic mutations in paediatric diffuse intrinsic pontine gliomas (DIPGs), we performed whole genome sequencing of 7 DIPGs and matched germline DNA, and targeted sequencing of an additional 43 DIPGs and 36 non-brainstem paediatric glioblastomas (non-BS-PGs).  78% of DIPGs and 22% of non-BS-PGs contained K27M mutation in H3F3A, encoding histone H3.3, or the related HIST1H3B, encoding histone H3.1. An additional 14% of non-BS-PGs had somatic G34R H3F3A mutations.","abstract":"To identify somatic mutations in paediatric diffuse intrinsic pontine gliomas (DIPGs), we performed whole genome sequencing of 7 DIPGs and matched germline DNA, and targeted sequencing of an additional 43 DIPGs and 36 non-brainstem paediatric glioblastomas (non-BS-PGs).  78% of DIPGs and 22% of non-BS-PGs contained K27M mutation in H3F3A, encoding histone H3.3, or the related HIST1H3B, encoding histone H3.1. An additional 14% of non-BS-PGs had somatic G34R H3F3A mutations.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-04T17:28:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000193","title":"ADCC_Exome_Sequencing","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from Adenoid cystic carcinomas and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina GA massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of 50 matched human  Adenoid cystic carcinoma  samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with Adenoid cystic carcinoma development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-09T12:08:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000194","title":"Radiotherapy_induced_Sarcoma_exome","description":"Whole exome library making will be performed on genomic DNA derived from radiotherapy induced sarcoma samples and matched normal DNA from the same patients. Next Generation sequencing will be performed on the resulting libraries and mapped to build 37 of the human reference genome to facilitate the identification of mutations","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina massively parallel sequencing technology, we aim to sequence microRNAs plus the protein coding genome of a number of matched human Chondrosarcoma samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-09T12:35:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000195","title":"Breast_Cancer_Somatic_Genetics_Study_","description":"We propose to definitively characterise the somatic genetics of ER+ve, HER2-ve breast cancer through generation of comprehensive catalogues of somatic mutations in 500 cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-10T12:44:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000196","title":"SCAT_osteosarcoma_sequencing","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 50 osteosarcoma cancers and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 100 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina GA massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of 50 matched human osteosarcoma samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with osteosarcoma development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-12T14:25:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000197","title":"ER___HER2___PR__breast_Cancer_genome_sequencing","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from X triple negative breast cancers and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting X exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina GA massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of X matched human breast cancer samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with triple negative breast cancer development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-12T16:17:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000198","title":"Myeloproliferative_Disorder_Sequencing","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 50 myeloproliferative disorder samples and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 100 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes. In addition, 500bp, NO_PCR total genomic libraries will be prepared from the same samples and five lanes of Illumina GA sequencing will be analysed to characterise genome wide, somatically acquired structural variation.","abstract":"Cancer is driven by mutation. Illumina GA massively parallel sequencing technology will be applied to Agilent exome hybridisation capture libraries and total genomic paired-end libraries from 50 matched human myeloproliferative disorder samples. Bespoke algorithms are being developed to identify the somatically acquired structural variants, point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with myeloproliferative disorder development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-12T16:21:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000199","title":"Myeloproliferative_Disorder_Sequencing","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 50 myeloproliferative disorder samples and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 100 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes. In addition, 500bp, NO_PCR total genomic libraries will be prepared from the same samples and five lanes of Illumina GA sequencing will be analysed to characterise genome wide, somatically acquired structural variation.","abstract":"Cancer is driven by mutation. Illumina GA massively parallel sequencing technology will be applied to Agilent exome hybridisation capture libraries and total genomic paired-end libraries from 50 matched human myeloproliferative disorder samples. Bespoke algorithms are being developed to identify the somatically acquired structural variants, point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with myeloproliferative disorder development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-12T16:24:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000200","title":"Acute_Lymphoblastic_Leukemia_Exome_sequencing_2_","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 50 Acute Lymphoblastic Leukemia samples and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 100 exome libraries and mapped build 37 of the human reference genome to facilitate the identification of novel cancer genes. In addition, 500bp, NO_PCR total genomic libraries will be prepared from the same samples and five lanes of Illumina GA sequencing will be analysed to characterise genome wide, somatically acquired structural variation.","abstract":"Cancer is driven by mutation. Illumina GA massively parallel sequencing technology will be applied to Agilent exome hybridisation capture libraries and total genomic paired-end libraries from 50 matched human Acute Lymphoblastic Leukemia samples. Bespoke algorithms are being developed to identify the somatically acquired structural variants, point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with Acute Lymphoblastic Leukemia development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-12T16:38:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000201","title":"Acute_Lymphoblastic_Leukemia_Exome_sequencing","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 50 Acute Lymphoblastic Leukemia samples and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 100 exome libraries and mapped build 37 of the human reference genome to facilitate the identification of novel cancer genes. In addition, 500bp, NO_PCR total genomic libraries will be prepared from the same samples and five lanes of Illumina GA sequencing will be analysed to characterise genome wide, somatically acquired structural variation.","abstract":"Cancer is driven by mutation. Illumina GA massively parallel sequencing technology will be applied to Agilent exome hybridisation capture libraries and total genomic paired-end libraries from 50 matched human Acute Lymphoblastic Leukemia samples. Bespoke algorithms are being developed to identify the somatically acquired structural variants, point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with Acute Lymphoblastic Leukemia development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-12T16:42:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000202","title":"Glioma_cell_lines_rearrangement_screen","description":"Genomic libraries (500 bps) will be generated from total genomic DNA derived from commomon epithelial cancer samples and subjected to total of eight lanes of 37 bp, paired end sequencing on the llumina GA. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemias, lymphomas and soft tissue tumors. However, conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution, thus the role of genomic rearrangement in common epithelial cancer is unknown. We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting common epithelial cancer genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-12T16:44:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000203","title":"ChIP_sequencing_in_Cancer_Cell_Lines","description":"The project is to evaluate the genomic binding sites of the histone demethylase JARID1C. This gene was recently identified in CGP as a novel recessive cancer gene in human renal cell carcinoma.","abstract":"The project is to evaluate the genomic binding sites of the histone demethylase JARID1C. This gene was recently identified in CGP as a novel recessive cancer gene in human renal cell carcinoma. These data are being generated in collaboration with Giovanni Tonin in Milan and will be used to pilot the approach and utility of this line of investigation.If successful, the data will produce a genome-wide map of potentially relevant sites regulating genes that are of potential interest in renal cancer biology.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-12T16:49:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000204","title":"Cancer_Plasma_DNA_Sequencing","description":"DNA can be successfully isolated from blood plasma. Such molecules are typically fragmented and may be by-products of cellular apoptosis or other cell death. A number of cancer genomes exhibit structural variation. This typically results in dramatic changes in copy number that distinguish normal and tumour cell genomes.  These structural variants can be rapidly identified by next generation sequencing platforms. In this proof of principle project we look for evidence of the cancer genome in sequence data obtained from the high throughput sequencing of patient plasma DNA.","abstract":"DNA can be successfully isolated from blood plasma. Such molecules are typically fragmented and may be by-products of cellular apoptosis or other cell death. A number of cancer genomes exhibit structural variation. This typically results in dramatic changes in copy number that distinguish normal and tumour cell genomes.  These structural variants can be rapidly identified by next generation sequencing platforms. In this proof of principle project we look for evidence of the cancer genome in sequence data obtained from the high throughput sequencing of patient plasma DNA.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000205","title":"Non_Tumour_Renal_Cell_Line_Sequencing","description":"Genomic libraries (500 bps) will be generated from total genomic DNA derived from commomon epithelial cancer samples and subjected to total of eight lanes of 37 bp, paired end sequencing on the llumina GA. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemias, lymphomas and soft tissue tumors. However, conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution, thus the role of genomic rearrangement in common epithelial cancer is unknown. We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting common epithelial cancer genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-12T17:26:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000206","title":"Cancer_Exome_Resequencing","description":"Genomic libraries (500 bps) will be generated from  total genomic DNA derived from a range of cancer samples and subjected paired end sequencing on the llumina GA. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"Cancer is driven by mutation. Illumina GA massively parallel sequencing technology will be applied to Agilent exome hybridisation capture libraries and total genomic paired-end libraries from a range of cancer samples. Bespoke algorithms are being developed to identify the somatically acquired structural variants, point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with  cancer development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-12T17:27:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000207","title":"Breast_Cancer_Exome_Resequencing","description":"Agilent whole exome hybridisation capture was performed on genomic DNA derived from Chondrosarcoma cancer and matched normal DNA from the same patients. Next Generation sequencing performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes. Now we aim to re find and validate the findings of those exome libraries using bespoke pulldown methods and sequencing the products.","abstract":"Cancer is driven by mutation. Illumina GA massively parallel sequencing technology will be applied to Agilent exome hybridisation capture libraries and total genomic paired-end libraries from a range of cancer samples. Bespoke algorithms are being developed to identify the somatically acquired structural variants, point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with  cancer development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-12T17:30:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000208","title":"Cancer_Genome_Libraries_Tests","description":"Testing library production.Genomic libraries (500 bps) will be generated from  total genomic DNA derived from commomon epithelial cancer samples and subjected to paired end sequencing on the llumina plateforms. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemias, lymphomas and soft tissue tumors. However, conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution, thus the role of genomic rearrangement in common epithelial cancer is unknown. We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting common epithelial cancer genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-12T17:36:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000209","title":"Acute_Myeloid_Leukemia_Sequencing","description":"Genomic libraries (500 bps) will be generated from  total genomic DNA derived from 25 acute myeloid leukemia  samples and subjected to total of eight lanes of 37 bp, paired end sequencing on the llumina GA. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemias, lymphomas and soft tissue tumors. To further explore role role of rearrangement in Acute myeloid leukemia,  we aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting acute myeloid leukemia  genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-12T17:40:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000210","title":"Breast_Cancer_Whole_Genome_Sequencing","description":"We propose to definitively characterise the somatic genetics of ER+ve, HER2-ve breast cancer through generation of comprehensive catalogues of somatic mutations in 500 cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-13T11:25:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000211","title":"Breast_Cancer_Exome_Sequencing","description":"Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 100 breast cancers of all subtypes and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 200 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina GA massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of 100 matched human breast cancer samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with breast cancer development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-13T11:25:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000212","title":"MuTHER_adipose_tissue_small_RNA_expression","description":"We investigate the naturally occurring variation of small RNA expression in conjunction with genetic and gene expression variation. We shall assess the variation in subabdominal fat tissue small RNA levels in 168 unrelated MuTHER individuals. Using gene expression data from the same samples, we can survey how much the small RNA expression contributes to the variance in gene expression profiles. We can also take advantage of the high density genotyping data on these samples to identify genetic associations of small RNA expression levels, and the downstream effect of the genetic variants in small RNA sequence. Previous small RNA sequencing efforts have also extended the repertoire of small RNAs, and we hope to potentially find additional small RNAs active in adipose tissue biology. Altogether, the project should provide an exciting view into small RNA biology in humans, and lead to development of new methodology for analysis of molecular phenotype data.","abstract":"We investigate the naturally occurring variation of small RNA expression in conjunction with genetic and gene expression variation. We shall assess the variation in subabdominal fat tissue small RNA levels in 168 unrelated MuTHER individuals. Using gene expression data from the same samples, we can survey how much the small RNA expression contributes to the variance in gene expression profiles. We can also take advantage of the high density genotyping data on these samples to identify genetic associations of small RNA expression levels, and the downstream effect of the genetic variants in small RNA sequence. Previous small RNA sequencing efforts have also extended the repertoire of small RNAs, and we hope to potentially find additional small RNAs active in adipose tissue biology. Altogether, the project should provide an exciting view into small RNA biology in humans, and lead to development of new methodology for analysis of molecular phenotype data.","study_type":"Transcriptome Analysis","pubmed_ids":[22589741],"external_links":null,"is_released":true,"released_date":"2012-01-13T12:14:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000213","title":"Association of Age at Diagnosis and Genetic Mutations in Patients with Neuroblastoma","description":"Neuroblastoma is diagnosed over a wide age range from birth through young adulthood, and older age at diagnosis is associated with a decline in survivability. We performed whole genome sequencing of DNA from diagnostic tumors and their matched germlines from 40 patients with metastatic neuroblastoma obtained between 1987 and 2009.  To identify genetic lesions that are associated with age at diagnosis in patients with metastatic neuroblastoma. Age groups at diagnosis included infants (0-18 months), children (18 months-12 years), and adolescents and young adults (&gt;12 years). To confirm the findings from this discovery cohort, validation testing using tumors from an additional 64 patients obtained between 1985 and 2009 was also performed.  Formalin-fixed paraffin-embedded tumor tissue was used for immunohistochemistry and fluorescent in situ hybridization.  Telomere lengths were analyzed using the whole genome sequencing data, quantitative polymerase chain reaction and fluorescent in situ hybridization","abstract":"Neuroblastoma is diagnosed over a wide age range from birth through young adulthood, and older age at diagnosis is associated with a decline in survivability. We performed whole genome sequencing of DNA from diagnostic tumors and their matched germlines from 40 patients with metastatic neuroblastoma obtained between 1987 and 2009.  To identify genetic lesions that are associated with age at diagnosis in patients with metastatic neuroblastoma. Age groups at diagnosis included infants (0-18 months), children (18 months-12 years), and adolescents and young adults (&gt;12 years). To confirm the findings from this discovery cohort, validation testing using tumors from an additional 64 patients obtained between 1985 and 2009 was also performed.  Formalin-fixed paraffin-embedded tumor tissue was used for immunohistochemistry and fluorescent in situ hybridization.  Telomere lengths were analyzed using the whole genome sequencing data, quantitative polymerase chain reaction and fluorescent in situ hybridization","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-25T18:44:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000214","title":"Test_of_PCR_library_method_on_whole_genmoe_samples","description":"We will sequence 2 whole genome pairs which have had the libraries prepared with a PCR step. The resulting sequence will be compared to teh same samples which have had sequence obtain using a no_PCR library method. the sequence obtained in this experiment may or may not be used in conjunction with the other sequence obtain for these samples in the search for novel cancer mutations.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-27T10:17:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000215","title":"ICGC PedBrain: Deep-sequencing of childhood brain tumors.","description":"Brain tumors constitute the childhood tumors with the highest mortality rates and survival is often associated with severe long-term sequelae due to intensive multimodal treatment regimens. Thus, the PedBrainTumor network aims at the identification of robust biomarkers for clinical management and novel molecular targets for therapeutic interventions. Using massively parallel whole-genome sequencing, and transcriptome and methylome sequencing for subsets of cases, we aim to decipher the molecular causes of medulloblastoma as well as low-grade astrocytoma, and to identify markers to stratify patients for specialized treatment. As the PedBrain network is affiliated with clinical trials in medulloblastoma and pilocytic astrocytoma, validation cohorts for the translation of key findings into clinical settings are readily available.","abstract":"Brain tumors constitute the childhood tumors with the highest mortality rates and survival is often associated with severe long-term sequelae due to intensive multimodal treatment regimens. Thus, the PedBrainTumor network aims at the identification of robust biomarkers for clinical management and novel molecular targets for therapeutic interventions. Using massively parallel whole-genome sequencing, and transcriptome and methylome sequencing for subsets of cases, we aim to decipher the molecular causes of medulloblastoma as well as low-grade astrocytoma, and to identify markers to stratify patients for specialized treatment. As the PedBrain network is affiliated with clinical trials in medulloblastoma and pilocytic astrocytoma, validation cohorts for the translation of key findings into clinical settings are readily available.","study_type":"Whole Genome Sequencing","pubmed_ids":[22832583],"external_links":null,"is_released":true,"released_date":"2012-01-27T15:08:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000216","title":"Melanoma_TIL_Study_Exomes","description":"In this study, mutations present in a series of human melanomas (stage IV disease) will be determined, using autologous blood cells to obtain a reference genome. From each of teh samples that are analyzed, tumour-infiltrating T lymphocytes have also been isolated. This offers a unique opportunity to determine which (fraction of) mutations in human cancer leads to epitopes that are recognized by T cells. The resulting information is likely to be of value to understand how T cell activating drugs exert their action.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-01-31T17:17:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000217","title":"Exome-sequencing identifies new oncogenes and tumor suppressor genes recurrently altered in hepatocellular carcinoma","description":"Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. High-resolution copy number analysis of 125 tumors of which 24 were subjected to whole-exome sequencing identified 135 homozygous deletions and 994 somatic gene mutations with predicted functional consequences. We identified new recurrent alterations in 4 genes (ARID1A, RPS6KA3, NFE2L2 and IRF2) not previously described in HCC. Functional analyses demonstrated tumor suppressor properties for IRF2 whose inactivation, exclusively found in hepatitis B virus related tumors, leads to impaired TP53 function. Alternatively, inactivation of proteins involved in chromatin remodeling was frequent and predominant in alcohol related tumors. Moreover, activation of the oxidative stress metabolism and inactivation of RPS6KA3 were new pathways associated with WNT/beta-catenin activation, thereby suggesting a cooperative effect in tumorigenesis. This study shows the dramatic somatic genetic diversity in HCC, it reveals interactions between oncogene and tumor suppressor gene mutations markedly related to specific risk factors.","abstract":"Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. High-resolution copy number analysis of 125 tumors of which 24 were subjected to whole-exome sequencing identified 135 homozygous deletions and 994 somatic gene mutations with predicted functional consequences. We identified new recurrent alterations in 4 genes (ARID1A, RPS6KA3, NFE2L2 and IRF2) not previously described in HCC. Functional analyses demonstrated tumor suppressor properties for IRF2 whose inactivation, exclusively found in hepatitis B virus related tumors, leads to impaired TP53 function. Alternatively, inactivation of proteins involved in chromatin remodeling was frequent and predominant in alcohol related tumors. Moreover, activation of the oxidative stress metabolism and inactivation of RPS6KA3 were new pathways associated with WNT/beta-catenin activation, thereby suggesting a cooperative effect in tumorigenesis. This study shows the dramatic somatic genetic diversity in HCC, it reveals interactions between oncogene and tumor suppressor gene mutations markedly related to specific risk factors.","study_type":"Exome Sequencing","pubmed_ids":[22561517,23264911,23945592],"external_links":null,"is_released":true,"released_date":"2012-02-01T11:33:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000218","title":"CML_Discovery_Project","description":"To identify mutations in CML","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-02-01T11:52:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000219","title":"X_linked_Developmental_Disease_Study","description":"DNA was extracted from Blood samples for an analysis of germline developmental delay.","abstract":"A study of familial X linked disease. Understanding the critical events underlying the developmental delay is paramount for advancing early detection and effective treatment. Extraordinary recent advances in sequencing now make it a realistic aim to sequence affected familial genomes to find these critical events.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000220","title":"Identifying_Novel_Fusion_Genes_in_Myeloma","description":"To identify novel fusion genes in Myeloma samples","abstract":"Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution. We aim to use massively parallel paired end sequencing to characterise the occurrence of critical genomic rearrangements for a selected sample set, understand the clonal evolution of those and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-02-03T10:02:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000221","title":"Transient_abnormal_myelopoeisis","description":"Deep resequencing of GATA1 Transient abnormal myelopoeisis in Downs syndrome patients.","abstract":"Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time.  Conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution. We aim to use massively parallel paired end sequencing to characterise the occurrence of critical genomic rearrangements for a selected sample set, understand the clonal evolution of those and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000222","title":"Whole Genome Sequencing of Neuroblastoma","description":"Neuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour1. Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%)2-5. Here we present a whole genome sequence analysis of 87 neuroblastoma of all stages. Only few recurrent amino-acid changing mutations were found. In contrast, analysis of structural defects identified in 18% of high stage neuroblastoma a local shredding of chromosomes, known as chromothripsis6. These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization7-9. In addition, ATRX, TIAM1 and a series of regulators of the Rac Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumors with defects in these genes were aggressive high stage neuroblastoma, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromotripsis and neuritogenesis gene alterations, which frequently occur in high risk tumors.","abstract":"Neuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour1. Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%)2-5. Here we present a whole genome sequence analysis of 87 neuroblastoma of all stages. Only few recurrent amino-acid changing mutations were found. In contrast, analysis of structural defects identified in 18% of high stage neuroblastoma a local shredding of chromosomes, known as chromothripsis6. These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization7-9. In addition, ATRX, TIAM1 and a series of regulators of the Rac Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumors with defects in these genes were aggressive high stage neuroblastoma, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromotripsis and neuritogenesis gene alterations, which frequently occur in high risk tumors.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-02-03T10:43:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000223","title":"Breast_cancer_fusion_gene_study","description":"To identify novel breast cancer fusion genes.","abstract":"Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution. We aim to use massively parallel paired end sequencing to characterise the occurrence of critical genomic rearrangements for a selected sample set, understand the clonal evolution of those and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000224","title":"Myelodysplastic_Syndrome_Follow_Up_Series","description":"Agilent whole exome hybridisation capture was performed on genomic DNA derived from MDS and matched normal DNA from the same patients. Next Generation sequencing performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes. Now we aim to discover the prevalence of our findings using bespoke pulldown methods and sequencing the products from a larger set of patient DNA.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-02-06T10:48:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000225","title":"UK10K NEURO GURLING","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. This sample set consists of DNA from multiply affected schizophrenia families. The families have been diagnosed using the SADS-L clinical instrument which gives diagnoses at the probable level of the research diagnostic criteria (RDC). In addition all diagnoses are available using DSMIIIR criteria. These criteria are widely accepted as being valid and reliable for the diagnosis of schizophrenia. All families have been collected to ensure that they are uni-lineal for transmission of schizophrenia, i.e. they have only one affected parent with schizophrenia, or a relative of only one transmitting or obligate carrier parent with schizophrenia. Families with bi-lineal transmission of schizophrenia (i.e. with both parents being affected) were not sampled for this study. All families have multiple cases of schizophrenia and related disorders. The families have been selected to ensure there are no cases of bipolar disorder within them and that they do not contain bipolar disorder in any relatives on either side of the family.For further information on this cohort please contact Hugh Gurling (h.gurling@ucl.ac.uk).","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. This sample set consists of DNA from multiply affected schizophrenia families. The families have been diagnosed using the SADS-L clinical instrument which gives diagnoses at the probable level of the research diagnostic criteria (RDC). In addition all diagnoses are available using DSMIIIR criteria. These criteria are widely accepted as being valid and reliable for the diagnosis of schizophrenia. All families have been collected to ensure that they are uni-lineal for transmission of schizophrenia, i.e. they have only one affected parent with schizophrenia, or a relative of only one transmitting or obligate carrier parent with schizophrenia. Families with bi-lineal transmission of schizophrenia (i.e. with both parents being affected) were not sampled for this study. All families have multiple cases of schizophrenia and related disorders. The families have been selected to ensure there are no cases of bipolar disorder within them and that they do not contain bipolar disorder in any relatives on either side of the family.For further information on this cohort please contact Hugh Gurling (h.gurling@ucl.ac.uk).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-02-10T10:30:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000226","title":"Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma","description":"Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases. To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (alpha-thalassaemia/mental retardation syndrome X-linked) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n=784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.","abstract":"Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases. To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (alpha-thalassaemia/mental retardation syndrome X-linked) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n=784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-02-10T11:29:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000227","title":"Validation_of_Raindance_technology_for_mutational_analysis_of_Human_Acute_Myeloid_Leukaemia","description":"Sequencing of 48 PCR products generated using Raindance technology in a single Illumina HiSeq lane. The PCR primers used to genertae these products carry Illumina HiSeq tails and are thus ready to sequence.","abstract":"Raindance technology uses a droplet-based PCR approach for the parallel amplification of multiple amplicons with primer pairs packaged in isolation from each other. This allows for over 1000 amplifications to be done simultaneously and may have advantages compared to pull-down approaches such as: 1) the ability to amplify repetitive regions, 2) less labour intensive, 3) less technically demanding and possibly 4) less costly. This work, will study 48 human acute myeloid leukaemia samples for the presence of mutations in 1 number of known leukaemia genes and will also compare Raindance &amp; Agilent-derived datasets in order to identify which technology works best in this context. Thus, as well as informing the AML field, this information will be useful to other scientists considering targeted re-sequencing approaches.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000228","title":"Whole_exome_sequencing_of_rare_autoimmune_related_phenotypes","description":"We aim to whole-exome sequence DNA samples from 75 individuals with severe forms of Inflammatory Bowel Disease and related autoimmune diseases to identify the rare, highly penetrant, variants that we believe underlie these phenotypes. Case samples will be obtained from both new and existing (UK IBD Genetics Consortium) collaborators to ensure only the most extreme cases are sequenced.","abstract":"We have access to DNA samples from individuals with severe forms of Inflammatory Bowel Disease and related autoimmune diseases.  We request funding to whole-exome sequence 100 such individuals to identify the rare, highly penetrant, variants that we believe underlie these phenotypes. The large number of IBD patients available within the UKIBDGC (12000+) ensures that we have tens of samples available across a range of very rare IBD-related phenotypes. These samples range from very severe forms of autoimmunity, such as a 4-year old boy with villous atrophy and severe diarrhea who doesn't produce immunoglobulins and with no B- cell precursors in his bone marrow, to more severe forms of typical IBD that do not respond to pharmaceutics or surgery. We expect the sequencing to take place over ~18 months, with 50 samples being sequenced in the first 6 months and then another 50 over the remaining 12 months. Samples drawn from the IIBDGC already have ethical approval and HMDMC documentation. The equivalent for non-UKIBDGC samples will be set up on a case-by-case basis as the samples come to our attention.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-02-13T12:47:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000229","title":"Genetic_background_for_cardio_vascular_disorders_in_the_general_Finnish_population","description":"Low coverage (4-6x) sequencing on samples from population cohorts (Finrisk, Health2000) will be done at Wellcome Trust Sanger Institute (WTSI) using Illumina HiSeq sequencing technology. We will produce 100bp paired end reads. Variants will be called using the 1000 Genomes Project pipeline.  The samples have been selected from a national representative set of approximately 30,300 samples and comprises 500 individuals of each gender in the extreme tail of high density lipoprotein (HDL) concentrations. Included individuals were between 25 and 65 years of age. Individuals with a diagnosis of diabetes or BMI&gt;30 were excluded from the study.","abstract":"Low coverage (4-6x) sequencing on samples from population cohorts (Finrisk, Health2000) will be done at Wellcome Trust Sanger Institute (WTSI) using Illumina HiSeq sequencing technology. We will produce 100bp paired end reads. Variants will be called using the 1000 Genomes Project pipeline.  The samples have been selected from a national representative set of approximately 30,300 samples and comprises 500 individuals of each gender in the extreme tail of high density lipoprotein (HDL) concentrations. Included individuals were between 25 and 65 years of age. Individuals with a diagnosis of diabetes or BMI&gt;30 were excluded from the study.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-02-13T13:54:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000230","title":"RNAseq_Pulldown_","description":"We propose to definitively characterise the somatic genetics of ER+ve, HER2-ve breast cancer through generation of comprehensive catalogues of somatic mutations in breast cancer cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses. In this experiment cDNA derived form Breast Cancer Cell lines was used in an Agilent whole exome pulldown experiment.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-02-14T16:09:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000231","title":"Assessment_of_genetic_and_epigenetic_variation_in_human_IPS_cells","description":"In order to progress human induced pluripotent stem cells (hiPSCs) towards the clinic, several outstanding questions must be addressed. It is possible to reprogram different somatic cell types into hiPSCs  but it is unclear whether some cell types carry through fewer mutations through reprogramming (either due to mutations present in the primary cells, or mutations accumulated during reprogramming). Through in depth analysis of hiPSCs generated from different somatic cells, it will be possible to assess the variation in genetic stability of different cell types.","abstract":"This study aims to understand the role of the somatic cell in reprogramming","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-02-15T16:52:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000232","title":"Low_coverage_sequencing_of_the_Fula_from_Gambia","description":"4X coverage for the Fula from Gambia.","abstract":"The purpose of the project is to support the discovery and understanding of genetic variants that influence human disease. Specifically defined goals are (a) the discovery of single nucleotide variants at frequencies of 1% or higher in diverse populations, (b) even more comprehensive discovery (variants down to frequencies of 0.1 - 0.5%) in functional gene regions, and (c) discovery of structural variants, such as copy number variants, other insertions and deletions, and inversions, including sequence-level understanding of breakpoints.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000233","title":"Pulldown_cytosine_deaminases","description":"We are looking at the causal factors behind hyper-mutator phenotypes found in previous Breast Cancer sequencing studies.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-02-24T13:28:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000234","title":"Low_coverage_sequencing_of_the_Jola_from_Gambia","description":"4X coverage for the Jola from Gambia.","abstract":"The purpose of the project is to support the discovery and understanding of genetic variants that influence human disease. Specifically defined goals are (a) the discovery of single nucleotide variants at frequencies of 1% or higher in diverse populations, (b) even more comprehensive discovery (variants down to frequencies of 0.1 - 0.5%) in functional gene regions, and (c) discovery of structural variants, such as copy number variants, other insertions and deletions, and inversions, including sequence-level understanding of breakpoints.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000235","title":"Low_coverage_sequencing_of_the_Woloff_from_Gambia","description":"4X coverage for the Woloff from Gambia.","abstract":"The purpose of the project is to support the discovery and understanding of genetic variants that influence human disease. Specifically defined goals are (a) the discovery of single nucleotide variants at frequencies of 1% or higher in diverse populations, (b) even more comprehensive discovery (variants down to frequencies of 0.1 - 0.5%) in functional gene regions, and (c) discovery of structural variants, such as copy number variants, other insertions and deletions, and inversions, including sequence-level understanding of breakpoints.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000236","title":"Low_coverage_sequencing_of_the_Mandinka_from_Gambia","description":"4X coverage for the Mandinka from Gambia.","abstract":"The purpose of the project is to support the discovery and understanding of genetic variants that influence human disease. Specifically defined goals are (a) the discovery of single nucleotide variants at frequencies of 1% or higher in diverse populations, (b) even more comprehensive discovery (variants down to frequencies of 0.1 - 0.5%) in functional gene regions, and (c) discovery of structural variants, such as copy number variants, other insertions and deletions, and inversions, including sequence-level understanding of breakpoints.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000237","title":"Ethiopia_Genome_Project__high_coverage_","description":"The Ethiopian area stands among the most ancient ones ever occupied by human populations and their ancestors. Particularly, according to archaeological evidences, it is possible to trace back the presence of Hominids up to at least 3 million years ago. Furthermore, the present day human populations show a great cultural, linguistic and historic diversity which makes them essential candidate to investigate a considerable part of the African variability. Following the typing of 300 Ethiopian samples on Illumina Omni 1M (see Human Variability in Ethiopia project, previously approved by the Genotyping committee) we now have a clearer idea on which populations living in the area include the most of the diversity.This project therefore aims to sequence the whole genome of 300 individuals at low (4-8x) depth belonging to the six most representative populations of the Ethiopian area to produce a unique catalogue of variants peculiar of the North East Africa. Furthermore 6 samples (one from each population) will also be sequenced at high  (30x) depth to ensure full coverage of the diversity spectrum.The retrieved variants will be of great help in evaluating the demographic dynamics of those populations as well as shedding light on the migrations out of Africa.","abstract":"High coverage (~30x) whole genome sequencing of Ethiopian individuals","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-01T08:19:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000238","title":"Ethiopia_Genome_Project__low_coverage_","description":"The Ethiopian area stands among the most ancient ones ever occupied by human populations and their ancestors. Particularly, according to archaeological evidences, it is possible to trace back the presence of Hominids up to at least 3 million years ago. Furthermore, the present day human populations show a great cultural, linguistic and historic diversity which makes them essential candidate to investigate a considerable part of the African variability. Following the typing of 300 Ethiopian samples on Illumina Omni 1M (see Human Variability in Ethiopia project, previously approved by the Genotyping committee) we now have a clearer idea on which populations living in the area include the most of the diversity.This project therefore aims to sequence the whole genome of 300 individuals at low (4-8x) depth belonging to the six most representative populations of the Ethiopian area to produce a unique catalogue of variants peculiar of the North East Africa. Furthermore 6 samples (one from each population) will also be sequenced at high  (30x) depth to ensure full coverage of the diversity spectrum.The retrieved variants will be of great help in evaluating the demographic dynamics of those populations as well as shedding light on the migrations out of Africa.","abstract":"Low coverage (~8x) whole genome sequencing of Ethiopian individuals","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-01T08:20:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000239","title":"Integrating_whole_genome_sequence_and_genotype_data_to_understand_rare_variants_and_mutational_processes_in_the_context_of_genome_wide_association_studies_of_cardiometabolic_traits","description":"In the context of genome wide association studies of cardiometabolic traits, we aim to sequence the whole genome of 8 related/unrelated individuals from the PROMIS and GPC KYA studies to about 25X coverage.","abstract":"In the context of genome wide association studies of cardiometabolic traits, we aim to sequence the whole genome of 8 related/unrelated individuals from the PROMIS and GPC KYA studies to about 25X coverage. In combination with other datasets, sequencing at this depth should help identify less common rare variants. We will combine whole genome sequence data with genotype data that we are already generating under the framework of other projects (internally approved and funded) to impute the genotypes for millions of additional variants beyond those directly genotyped. The imputed genotype data will allow us to localize the disease-associated regions more precisely and to better understand the role of less common variants in cardiometabolic disease. Additionally, as the rate of 'de novo' germline mutations will contribute to understanding disease processes, these data will support the study of mutational rates in humans, as part of a collaborative study at WTSI.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000240","title":"Whole_Exome_sequencing_in_a_large_IBD_pedigree","description":"We perform whole exome sequencing on samples from a large IBD pedigree. The selected samples are from more distantly related family members (healthy and with IBD) and a set of matched population (Ashkenazy Jewish ancestry) samples.","abstract":"We perform whole exome sequencing on samples from a large IBD pedigree. The selected samples are from more distantly related family members (healthy and with IBD) and a set of matched population (Ashkenazy Jewish ancestry) samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-01T08:31:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000241","title":"UK10K_exome_sequence__BIOBANK_samples","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The BIOBANK samples are part of the Obesity group and will undergo exome sequencing.","abstract":"UK Biobank is a longitudinal cohort of 500,000 people aged 40-69 from across the country, established to provide a resource for gene-environment studies across a wide range of health areas. From these large numbers we have selected 890 samples from subjects with extreme BMI at 2.5-3 standard deviations from the population mean.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000242","title":"UK10K_OBESITY_GS","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The GS samples are part of the Obesity group and will undergo exome sequencing.","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The GS samples are part of the Obesity group and will undergo exome sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-01T13:42:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000243","title":"Integrative_Oncogenomics_of_multiple_myeloma","description":"We used targeted capture and massively parallel sequencing of exomes of CD138 purified plasma cells and matched somatic DNA from 53 patients with Multiple Myeloma. 2281 variants were validated by 454 sequencing. The present study will validate an additional 5538 variants by targeted pull-down and sequencing. The normal and tumor samples will be indexed separately and pre-pooled in groups of 10 or 11. The sequence capture will use 5 reactions each for the normals and tumors. All normal samples will then be pooled and go thorugh one lane of HiSeq. Same for the tumors.","abstract":"Multiple myeloma (MM) is an incurable malignancy of post-germinal centre B-cells whose pathogenesis is only partially understood. Chromosomal abnormalities, such as hyperdiploidy and recurrent immunoglobulin gene locus rearrangements are frequent, but are thought to be insufficient for malignant transformation because they are also observed in the pre-malignant syndrome called monoclonal gammopathy of uncertain significance (MGUS), while malignant progression is often associated with additional events, like MYC activation. This implies that the genetic landscape of MM changes over time as result of additional events that define its emergence and progression.To investigate genomic event underlying MM pathogenesis, and how these correlate with known prognostic markers of the disease, we used targeted capture and massively parallel sequencing of exomes of CD138 purified plasma cells from 53 patients with MM. Exome reads were used to call substitutions and insertions/deletions. We used single nucleotide polymorphisms (SNPs) to infer chromosomal copy number and allelic ratio of the tumor. Lastly, mutation burden was used to estimate the clonal architecture of each sample and its evolution over time (where available). All data were produced by in-house algorithms developed at the Wellcome Trust Sanger Institute.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-12T16:36:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000244","title":"Integrative_Oncogenomics_of_multiple_myeloma","description":"We used targeted capture and massively parallel sequencing of exomes of CD138 purified plasma cells and matched somatic DNA from 17 patients with Multiple Myeloma. For each patient, an early tumor sample (at diagnosis) and a late one (at relapse) were available. For few of them, an additional late sample (2nd progression) was present. In total, the study has 52 samples. 1044 variants were validated by 454 sequencing. The present study will validate an additional 4630 variants by targeted pull-down and sequencing. All 52 samples will be indexed and then will be pre-pooled in groups of 5 or 6. The sequence capture will use 10 reactions. All samples will then be pooled and go thorugh one lane of HiSeq.","abstract":"Multiple myeloma (MM) is an incurable malignancy of post-germinal centre B-cells whose pathogenesis is only partially understood. Chromosomal abnormalities, such as hyperdiploidy and recurrent immunoglobulin gene locus rearrangements are frequent, but are thought to be insufficient for malignant transformation because they are also observed in the pre-malignant syndrome called monoclonal gammopathy of uncertain significance (MGUS), while malignant progression is often associated with additional events, like MYC activation. This implies that the genetic landscape of MM changes over time as result of additional events that define its emergence and progression.To investigate genomic event underlying MM pathogenesis, and how these correlate with known prognostic markers of the disease, we used targeted capture and massively parallel sequencing of exomes of CD138 purified plasma cells from 17 patients with MM. All patients had serial samples available (range 8-17 months apart). Exome reads were used to call substitutions and insertions/deletions. We used single nucleotide polymorphisms (SNPs) to infer chromosomal copy number and allelic ratio of the tumor. Lastly, mutation burden was used to estimate the clonal architecture of each sample and its evolution over time (where available). All data were produced by in-house algorithms developed at the Wellcome Trust Sanger Institute.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-12T16:36:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000245","title":"A Comprehensive Catalogue of Somatic Mutations from a Human Cancer Genome","description":"We previously reported the whole-genome sequencing of the well-studied human malignant melanoma cell line, COLO-829, and a lymphoblastoid cell line from the same individual, providing the first comprehensive catalogue of somatic mutations from an individual cancer (Pleasance et al. (2010) Nature 463, 191). This initial study was carried out using the Illumina Genome Analyzer II, largely using paired-end reads of 75 bases from standard Illumina paired-end libraries. Here we report the results of sequencing the genomes of COLO-829 and its matched lymphoblastoid sample using HiSeq2000 with v3 cluster-generation and sequencing chemistries. This has significantly improved the evenness and completeness of genomic coverage, particularly in areas of extreme sequence composition that were underrepresented in the initial study.","abstract":"We previously reported the whole-genome sequencing of the well-studied human malignant melanoma cell line, COLO-829, and a lymphoblastoid cell line from the same individual, providing the first comprehensive catalogue of somatic mutations from an individual cancer (Pleasance et al. (2010) Nature 463, 191). This initial study was carried out using the Illumina Genome Analyzer II, largely using paired-end reads of 75 bases from standard Illumina paired-end libraries. Here we report the results of sequencing the genomes of COLO-829 and its matched lymphoblastoid sample using HiSeq2000 with v3 cluster-generation and sequencing chemistries. This has significantly improved the evenness and completeness of genomic coverage, particularly in areas of extreme sequence composition that were underrepresented in the initial study.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-13T13:44:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000246","title":"Genetic landscape of pediatric Infant Acute Lymphoblastic leukemia","description":"We performed whole genome sequencing of tumor and normal DNA samples obtained from 22 infant ALL cases with MLL rearrangements. In addition, we sequenced 2 paired diagnostic-relapse samples. Using complementary pipelines, somatically acquired genetic changes were analyzed, including single nucleotide variations (SNVs), insertion/deletions, structural variations and copy number variations in the cancer genomes. In addition, exome sequencing was performed on paired diagnostic and normal DNA samples obtained from 20 cases of non-infant MLL rearranged leukemias and somatic mutations in the coding regions were identified.","abstract":"We performed whole genome sequencing of tumor and normal DNA samples obtained from 22 infant ALL cases with MLL rearrangements. In addition, we sequenced 2 paired diagnostic-relapse samples. Using complementary pipelines, somatically acquired genetic changes were analyzed, including single nucleotide variations (SNVs), insertion/deletions, structural variations and copy number variations in the cancer genomes. In addition, exome sequencing was performed on paired diagnostic and normal DNA samples obtained from 20 cases of non-infant MLL rearranged leukemias and somatic mutations in the coding regions were identified.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-14T14:21:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000247","title":"Whole genome sequencing, whole exome sequencing and RNAseq of rare melanoma subtypes","description":"Whole genome sequencing and whole exome sequencing of uveal, mucosal and acral melanomas and their matched germline DNA.  RNAseq of mRNA from the tumour samples.","abstract":"Whole genome sequencing and whole exome sequencing of uveal, mucosal and acral melanomas and their matched germline DNA.  RNAseq of mRNA from the tumour samples.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000248","title":"test UK10K_whole_genome_shotgun_sequence__TWINS_UK_cohort","description":"test UK10K_whole_genome_shotgun_sequence__TWINS_UK_cohort","abstract":"test UK10K_whole_genome_shotgun_sequence__TWINS_UK_cohort","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000249","title":"Genomic Alterations in Gingivo-buccal Cancer: ICGC-India Project_YR01","description":"As a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India.   There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection.  Paired DNA samples – isolated from the tumor tissue and from the blood of fifty patients – have been analyzed to catalog germline and somatic mutations. Association between each observed genomic alteration and exposure to environmental risk factors is being explored.Detailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from blood and tumor tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai.  Exome capture and deep resequencing are being performed at the National Institute of Biomedical Genomics, Kalyani. We have analyzed the exomes of paired blood and tumor DNA samples using two orthogonal platforms – exome capture by Roche-Nimblegen SeqCap Ez kit followed by sequencing on Roche-454 GS FLX, and exome capture by Illumina TrueSeq Exome Enrichment kit followed by sequencing on Illumina HiSeq-2000. Each exome is being sequenced at a mean depth of 30x. In addition, we have used Illumina Omni Quad SNP-chips to generate genotype data at 1.14 million genomic markers. The average concordance between SNP-chip and sequence data is 99.8%.","abstract":"As a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India.   There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection.  Paired DNA samples – isolated from the tumor tissue and from the blood of fifty patients – have been analyzed to catalog germline and somatic mutations. Association between each observed genomic alteration and exposure to environmental risk factors is being explored.Detailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from blood and tumor tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai.  Exome capture and deep resequencing are being performed at the National Institute of Biomedical Genomics, Kalyani. We have analyzed the exomes of paired blood and tumor DNA samples using two orthogonal platforms – exome capture by Roche-Nimblegen SeqCap Ez kit followed by sequencing on Roche-454 GS FLX, and exome capture by Illumina TrueSeq Exome Enrichment kit followed by sequencing on Illumina HiSeq-2000. Each exome is being sequenced at a mean depth of 30x. In addition, we have used Illumina Omni Quad SNP-chips to generate genotype data at 1.14 million genomic markers. The average concordance between SNP-chip and sequence data is 99.8%.","study_type":"Other","pubmed_ids":[24292195],"external_links":null,"is_released":true,"released_date":"2012-03-16T08:56:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000250","title":"Poikiloderma_syndrome_RNAseq","description":"We will sequence the RNA of lymphoblast samples, transformed with EBV, which have poikiloderma syndrome with mutations in c16orf57. The aim of the experiment is to characterise RNA structural effects in this disease.","abstract":"Poikiloderma is a condition that occurs most commonly on the neck and chest. It refers to the erythema (redness) and sun damage (pigment) associated with mottled, uneven or \"leathery\" looking skin.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-16T10:25:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000251","title":"Melanoma_Til_Study_RNAseq","description":"In this study, mutations present in a series of human melanomas (stage IV disease) will be determined, using autologous blood cells to obtain a reference genome. From each of the samples that are analyzed, tumour-infiltrating T lymphocytes have also been isolated. This offers a unique opportunity to determine which (fraction of) mutations in human cancer leads to epitopes that are recognized by T cells. The resulting information is likely to be of value to understand how T cell activating drugs exert their action.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-16T10:37:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000252","title":"Whole_genome_sequencing_of_Italian_genetic_isolates__Friuli_Venezia_Giulia","description":"Low coverage whole genome sequencing of samples from individuals from Friuli Venezia Giulia, an Italian genetic isolate population.","abstract":"Low coverage whole genome sequencing of samples from individuals from Friuli Venezia Giulia, an Italian genetic isolate population.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-16T16:17:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000253","title":"Whole genome sequencing of pediatric BCR-ABL1 positive acute lymphoblastic leukemia","description":"We performed whole-genome sequencing of 18 paired tumor/normal BCR-ABL1+ leukemia genomes and analyzed single nucleotide variations (SNVs), insertion/deletions, structural variations and copy number variations in the tumor and normal genomes","abstract":"We performed whole-genome sequencing of 18 paired tumor/normal BCR-ABL1+ leukemia genomes and analyzed single nucleotide variations (SNVs), insertion/deletions, structural variations and copy number variations in the tumor and normal genomes","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-20T15:41:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000254","title":"Genetic landscape of pediatric ependymoma","description":"We performed whole-genome sequencing of 42 paired tumor/normal EPD genomes and analyzed somatically acquired single nucleotide variations (SNVs), insertion/deletions, structural variations and copy number variations in the cancer genomes","abstract":"We performed whole-genome sequencing of 42 paired tumor/normal EPD genomes and analyzed somatically acquired single nucleotide variations (SNVs), insertion/deletions, structural variations and copy number variations in the cancer genomes","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-20T15:45:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000255","title":"Genetic landscape of pediatric Low Grade Gliomas & Glioneuronal tumors","description":"We performed whole-genome sequencing of 42 paired tumor/normal LGG genomes and analyzed somatically acquired single nucleotide variations (SNVs), insertion/deletions, structural variations and copy number variations in the cancer genomes","abstract":"We performed whole-genome sequencing of 42 paired tumor/normal LGG genomes and analyzed somatically acquired single nucleotide variations (SNVs), insertion/deletions, structural variations and copy number variations in the cancer genomes","study_type":"Whole Genome Sequencing","pubmed_ids":[23583981,24076604],"external_links":null,"is_released":true,"released_date":"2012-03-20T15:49:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000256","title":"Genetic landscape of pediatric Rhabdomyosarcoma","description":"We performed whole-genome sequencing of 13 paired tumor/normal Rhabdomyosarcoma genomes and analyzed somatically acquired single nucleotide variations SNVs, insertion/deletions, structural variations and copy number variations in the cancer genomes","abstract":"We performed whole-genome sequencing of 13 paired tumor/normal Rhabdomyosarcoma genomes and analyzed somatically acquired single nucleotide variations SNVs, insertion/deletions, structural variations and copy number variations in the cancer genomes","study_type":"Other","pubmed_ids":[24332040],"external_links":null,"is_released":true,"released_date":"2012-03-20T15:52:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000257","title":"Genetic landscape of pediatric Adrenocortical Tumor","description":"Paediatric adrenocortical carcinoma is a rare malignancy with poor prognosis. Here we analyse 37 adrenocortical tumours (ACTs) by whole-genome, whole-exome and/or transcriptome sequencing. Collectively, these findings demonstrate the nature, timing and potential prognostic significance of key genetic alterations in paediatric ACT and outline a hypothetical model of paediatric adrenocortical tumorigenesis.","abstract":"Paediatric adrenocortical carcinoma is a rare malignancy with poor prognosis. Here we analyse 37 adrenocortical tumours (ACTs) by whole-genome, whole-exome and/or transcriptome sequencing. Collectively, these findings demonstrate the nature, timing and potential prognostic significance of key genetic alterations in paediatric ACT and outline a hypothetical model of paediatric adrenocortical tumorigenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-20T15:57:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000258","title":"Integrative genomic analyses reveal androgen-driven somatic alteration landscape in early-onset prostate cancer","description":"DEPRECATED: this EGA Study represents an earlier - draft - version of this paper.\nFor the dataset used in the final published version of the paper, please see https://ega-archive.org/studies/EGAS00001000400.","abstract":"DEPRECATED: this EGA Study represents an earlier - draft - version of this paper.\nFor the dataset used in the final published version of the paper, please see https://ega-archive.org/studies/EGAS00001000400.","study_type":"Other","pubmed_ids":[23410972],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001000260","title":"Targeted_Pulldown_Validation_of_mutations_found_in_whole_genome_sequencing","description":"This experiment is to inform us of the validity of using pre-made library material to perform a bespoke pulldown experiment to validate the mutations found between the whole genome sequencing of the DNA from the same individuals cancer and normal material. This is to identify the valid and informative mutations in cancer genomes.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-22T13:14:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000261","title":"Transcriptome_Sequencing_of_Cancer_Cell_Lines","description":"In this study we will sequence the transcriptome of Verified Cancer Cell lines. This will be married up to whole exome and whole genome sequencing data to establish a full catalog of the variations and mutations found.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-22T14:18:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000262","title":"CRUK-ICGC Prostate Cancer Group Study","description":"Prostate cancer somatic genomic sequencing data generated from 2011 onwards under auspices of the International Cancer Genome Consortium Prostate Cancer UK consortium (CRUK-ICGC Prostate Group), co-led by Colin Cooper and Ros Eeles, with other Principal Investigators (Brewer, Neal, Bova, McDermott, Wedge, Lynch, Massie, and Foster) and others as listed in study publications. Funded by Cancer Research UK and other funders as listed in study publications.  Contents and publications related to each dataset are described with each dataset (EGAD) entry.\nOur study was funded with the ambition of collecting Whole Genome DNA sequence data from 250 prostate cancers, with matching transcriptome and methylome data.\n The original aims of the project were:\n1.To understand the significance of multifocal prostate cancer. \n2.To understand the clinical heterogeneity of prostate cancer to devise markers for predicting outcome and for drug targeting.\n3.To understand the molecular basis of development and spread of castration-resistant and metastatic disease \n4.To understand the aetiology of prostate cancer particularly the large variation in incidences that occur in different populations and ethnic groups. \nPlease see https://doi.org/10.5281/zenodo.4022439 for links between sample IDs reported in literature and EGA IDs.","abstract":"Prostate cancer somatic genomic sequencing data generated from 2011 onwards under auspices of the International Cancer Genome Consortium Prostate Cancer UK consortium (CRUK-ICGC Prostate Group), co-led by Colin Cooper and Ros Eeles, with other Principal Investigators (Brewer, Neal, Bova, McDermott, Wedge, Lynch, Massie, and Foster) and others as listed in study publications. Funded by Cancer Research UK and other funders as listed in study publications.  Contents and publications related to each dataset are described with each dataset (EGAD) entry.\nOur study was funded with the ambition of collecting Whole Genome DNA sequence data from 250 prostate cancers, with matching transcriptome and methylome data.\n The original aims of the project were:\n1.To understand the significance of multifocal prostate cancer. \n2.To understand the clinical heterogeneity of prostate cancer to devise markers for predicting outcome and for drug targeting.\n3.To understand the molecular basis of development and spread of castration-resistant and metastatic disease \n4.To understand the aetiology of prostate cancer particularly the large variation in incidences that occur in different populations and ethnic groups. \nPlease see https://doi.org/10.5281/zenodo.4022439 for links between sample IDs reported in literature and EGA IDs.","study_type":"Other","pubmed_ids":[29662167],"external_links":null,"is_released":true,"released_date":"2012-03-23T14:08:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000263","title":"Genetic landscape of pediatric Osteosarcoma","description":"We performed whole-genome sequencing of 37 paired tumor/normal OS genomes and analyzed somatically acquired single nucleotide variations (SNVs), insertion/deletions, structural variations and copy number variations in the cancer genomes","abstract":"We performed whole-genome sequencing of 37 paired tumor/normal OS genomes and analyzed somatically acquired single nucleotide variations (SNVs), insertion/deletions, structural variations and copy number variations in the cancer genomes","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-26T14:12:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000264","title":"Shwachman_Diamond_syndrome__SDS___Exome_sequencing","description":"Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, leukemia predisposition, and skeletal abnormalities. We aim to characterise the structural effects of SDS in patients with this disorder by exome sequencing.","abstract":"Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, leukemia predisposition, and skeletal abnormalities.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-26T17:01:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000266","title":"Exome_sequencing_of_patients_with_Ewings_sarcoma_","description":"Cancer is driven by mutations in the genome. We will uncover the mutations that give rise to Ewing’s sarcoma, a bone tumour that largely affects children. We will use second generation Illumina massively parallel sequencing, and bespoke software, to characterise the genomes and transcriptomes of Ewings’ sarcoma tumours.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina massively parallel sequencing technology, we aim to sequence microRNAs plus the protein coding genome of a number of matched human Cancer/Normal samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-26T17:02:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000267","title":"RNAseq_of_patients_with_Ewings_sarcoma","description":"Cancer is driven my mutations in the genome. We will uncover the mutations that give rise to Ewing’s sarcoma, a bone tumour that largely affects children. We will use second generation Illumina massively parallel sequencing, and bespoke software, to characterise the genomes and transcriptomes of Ewings’ sarcoma tumours.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-26T17:02:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000268","title":"Accurate mutation detection in leukemia by re-sequencing a cancer gene set","description":"With the advent of whole-genome and whole-exome sequencing, high-quality catalogs of recurrently mutated cancer genes are becoming available for many cancer types. Increasing access to sequencing technology, including bench-top sequencers, provide the opportunity to re-sequence a limited set of cancer genes across a patient cohort with limited processing time. Here, we re-sequenced a set of cancer genes in T-cell acute lymphoblastic leukemia (T-ALL) using the Roche/454 technology coupled with Nimblegen sequence capture. First, we investigated how a maximal sensitivity and specificity of mutation detection can be achieved through a benchmark study. We tested nine combinations of different mapping and variant-calling methods, varied the variant calling parameters, and compared the predicted mutations with a large independent validation set obtained by capillary re-sequencing. We found that the combination of two mapping algorithms, namely BWA-SW and SSAHA2, coupled with the variant calling algorithm Atlas-SNP2 yields the highest sensitivity (95%) and the highest specificity (93%). Next, we applied this analysis pipeline to identify mutations in a set of 58 cancer genes, in a panel of 18 T-ALL cell lines and 15 T-ALL patient samples. We confirmed mutations in known T-ALL drivers, including PHF6, NF1, FBXW7, NOTCH1, KRAS, NRAS, PIK3CA, and PTEN. Interestingly, we also found mutations in several cancer genes that had not been linked to T-ALL before, including JAK3. Finally, we re-sequenced a small set of 39 candidate genes and identified recurrent mutations in TET1, SPRY3 and SPRY4. In conclusion, we established an optimized analysis pipeline for Roche/454 data that can be applied to accurately detect gene mutations in cancer, which led to the identification of several new candidate T-ALL driver mutations.","abstract":"With the advent of whole-genome and whole-exome sequencing, high-quality catalogs of recurrently mutated cancer genes are becoming available for many cancer types. Increasing access to sequencing technology, including bench-top sequencers, provide the opportunity to re-sequence a limited set of cancer genes across a patient cohort with limited processing time. Here, we re-sequenced a set of cancer genes in T-cell acute lymphoblastic leukemia (T-ALL) using the Roche/454 technology coupled with Nimblegen sequence capture. First, we investigated how a maximal sensitivity and specificity of mutation detection can be achieved through a benchmark study. We tested nine combinations of different mapping and variant-calling methods, varied the variant calling parameters, and compared the predicted mutations with a large independent validation set obtained by capillary re-sequencing. We found that the combination of two mapping algorithms, namely BWA-SW and SSAHA2, coupled with the variant calling algorithm Atlas-SNP2 yields the highest sensitivity (95%) and the highest specificity (93%). Next, we applied this analysis pipeline to identify mutations in a set of 58 cancer genes, in a panel of 18 T-ALL cell lines and 15 T-ALL patient samples. We confirmed mutations in known T-ALL drivers, including PHF6, NF1, FBXW7, NOTCH1, KRAS, NRAS, PIK3CA, and PTEN. Interestingly, we also found mutations in several cancer genes that had not been linked to T-ALL before, including JAK3. Finally, we re-sequenced a small set of 39 candidate genes and identified recurrent mutations in TET1, SPRY3 and SPRY4. In conclusion, we established an optimized analysis pipeline for Roche/454 data that can be applied to accurately detect gene mutations in cancer, which led to the identification of several new candidate T-ALL driver mutations.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-29T10:08:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000269","title":"Identification_of_the_underlying_causal_variant_in_a_multi_generational_family_with_autosomal_dominant_common_variable_immunodeficiency","description":"Common variable immunodeficiency (CVID) is the most common form of primary immunodeficiency with an estimated incidence of 1:10,000. It has been apparent for many years that CVID has a genetic component, occurs frequently in families and can have both a recessive or dominant mode of inheritance. In recent years, 4 genes underlying CVID have been identified; however, mutations within in them are estimated to account for no more than 10% of all cases of CVID.We have identified a multi-generational family with autosomal dominant CVID. Genome-wide linkage analysis has mapped the locus underlying CVID in this family to an approximately 9.2 Mb interval on chromosome 3q27.3-q29, between the markers D3S3570 and D3S1265. This locus is distinct from any of the previously mapped susceptibility loci suggesting a novel genetic variant is responsible for disease in this family. The aim of this study is to use exome sequencing of affected (n = 4) and unaffected (n = 4) individuals, in tandem with the available genetic mapping data, to identify the causal variant underlying CVID in this family.","abstract":"Common variable immunodeficiency (CVID) is the most common form of primary immunodeficiency with an estimated incidence of 1:10,000. It has been apparent for many years that CVID has a genetic component, occurs frequently in families and can have both a recessive or dominant mode of inheritance. In recent years, 4 genes underlying CVID have been identified; however, mutations within in them are estimated to account for no more than 10% of all cases of CVID.We have identified a multi-generational family with autosomal dominant CVID. Genome-wide linkage analysis has mapped the locus underlying CVID in this family to an approximately 9.2 Mb interval on chromosome 3q27.3-q29, between the markers D3S3570 and D3S1265. This locus is distinct from any of the previously mapped susceptibility loci suggesting a novel genetic variant is responsible for disease in this family. The aim of this study is to use exome sequencing of affected (n = 4) and unaffected (n = 4) individuals, in tandem with the available genetic mapping data, to identify the causal variant underlying CVID in this family.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-03-29T12:08:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000270","title":"miseq_wettest_2","description":"test","abstract":"test","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000271","title":"Comparing sequencing of four proto-typical Burkitt lymphomas (BL) with IG-MYC translocation.","description":"By whole-genome, exome, transcriptome and methylome sequencing of four proto-typical Burkitt lymphomas (BL) with IG-MYC translocation we identified seven recurrently mutated genes including ID3. In an extended cohort, 36/53 (68%) molecularly-defined BL carried potentially damaging mutations of ID3 which were enriched at somatic hypermutation motifs. Only 6/47 (13%) other IG-MYC-positive B-cell lymphomas carried ID3 mutations suggesting cooperation of ID3 inactivation and IG-MYC translocation to be a hallmark of Burkitt lymphomagenesis.","abstract":"By whole-genome, exome, transcriptome and methylome sequencing of four proto-typical Burkitt lymphomas (BL) with IG-MYC translocation we identified seven recurrently mutated genes including ID3. In an extended cohort, 36/53 (68%) molecularly-defined BL carried potentially damaging mutations of ID3 which were enriched at somatic hypermutation motifs. Only 6/47 (13%) other IG-MYC-positive B-cell lymphomas carried ID3 mutations suggesting cooperation of ID3 inactivation and IG-MYC translocation to be a hallmark of Burkitt lymphomagenesis.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-04-17T10:14:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000272","title":"Whole Genome Methylation in CLL","description":"We have extensively characterized the DNA methylome of chronic lymphocytic leukemia (CLL) with mutated and unmutated IGHV as well as several mature B cell subpopulations using whole-genome bisulfite sequencing and high-density microarrays.","abstract":"We have extensively characterized the DNA methylome of chronic lymphocytic leukemia (CLL) with mutated and unmutated IGHV as well as several mature B cell subpopulations using whole-genome bisulfite sequencing and high-density microarrays.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-04-17T12:39:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000273","title":"Stratifying and Targeting Pediatric Medulloblastoma through Genomics","description":"In this project, genomic analyses of pediatric medulloblastoma samples, obtained through the international medulloblastoma consortium, will be performed. RNA and miRNA expression profiles of 1000 samples, representing all four subgroups (Wnt, Shh, Group C, and D), will be studied to identify novel subtypes within each subgroup. The resulting subtype-specific expression profiles will support the development of reliable and robust biomarkers to more accurately and reliably classify medulloblastomas for treatment in clinical trials. For that purpose, two assays will be developed: an antibody-based immunohistochemical assay and an orthogonal nucleic acid-based hybridization assay.\nAdditional genomic DNA analysis of the 300 high risk subgroup cases will support the discovery of subgroup specific somatic mutations in order to inform current clinical trials of targeted therapies, and to identify genes and pathways already targeted in other diseases. Such therapies could be rapidly transitioned to Phase II trials in medulloblastoma. Furthermore, the discovery of somatic mutations could be used for developing as well as validating specific biomarkers.\nThe project team will also try to identify risk factors that predispose children to this type of cancer.","abstract":"In this project, genomic analyses of pediatric medulloblastoma samples, obtained through the international medulloblastoma consortium, will be performed. RNA and miRNA expression profiles of 1000 samples, representing all four subgroups (Wnt, Shh, Group C, and D), will be studied to identify novel subtypes within each subgroup. The resulting subtype-specific expression profiles will support the development of reliable and robust biomarkers to more accurately and reliably classify medulloblastomas for treatment in clinical trials. For that purpose, two assays will be developed: an antibody-based immunohistochemical assay and an orthogonal nucleic acid-based hybridization assay.\nAdditional genomic DNA analysis of the 300 high risk subgroup cases will support the discovery of subgroup specific somatic mutations in order to inform current clinical trials of targeted therapies, and to identify genes and pathways already targeted in other diseases. Such therapies could be rapidly transitioned to Phase II trials in medulloblastoma. Furthermore, the discovery of somatic mutations could be used for developing as well as validating specific biomarkers.\nThe project team will also try to identify risk factors that predispose children to this type of cancer.","study_type":"Other","pubmed_ids":[22832581,24954133,26760213,26977882,27058758],"external_links":null,"is_released":true,"released_date":"2012-04-20T01:21:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000274","title":"Coverage bias and sensitivity of variant calling for four whole-genome sequencing technologies","description":"Massively parallel sequencing has revolutionized research in cancer genetics and genomics and enhanced our understanding of natural human genetic variation. Recently, Lam et al. have performed a detailed comparison of two next-generation sequencing technologies with respect to their sensitivity to call single nucleotide variants (SNV) and indels. Here, we sequenced two tumor/normal pairs obtained from two paedriatic medulloblastoma patients with Life Technologies’ SOLiD 4 and 5500xl SOLiD, Illumina’s HiSeq2000, and Complete Genomics’ technology.  We then compared their ability to call SNVs with high confidence. As gold standard for SNV calling, we used genotypes determined by an Affymetrix SNP array. Additionally, we performed a detailed analysis of how evenly each technology covers the genome and how the reads are distributed across functional genomic regions. Finally, we studied how a combination of data from different technologies might help to overcome the limitations in SNV calling by any of the four technologies alone.","abstract":"Massively parallel sequencing has revolutionized research in cancer genetics and genomics and enhanced our understanding of natural human genetic variation. Recently, Lam et al. have performed a detailed comparison of two next-generation sequencing technologies with respect to their sensitivity to call single nucleotide variants (SNV) and indels. Here, we sequenced two tumor/normal pairs obtained from two paedriatic medulloblastoma patients with Life Technologies’ SOLiD 4 and 5500xl SOLiD, Illumina’s HiSeq2000, and Complete Genomics’ technology.  We then compared their ability to call SNVs with high confidence. As gold standard for SNV calling, we used genotypes determined by an Affymetrix SNP array. Additionally, we performed a detailed analysis of how evenly each technology covers the genome and how the reads are distributed across functional genomic regions. Finally, we studied how a combination of data from different technologies might help to overcome the limitations in SNV calling by any of the four technologies alone.","study_type":"Whole Genome Sequencing","pubmed_ids":[23776689],"external_links":null,"is_released":true,"released_date":"2012-04-23T09:02:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000275","title":"AML_targeted_resequencing_study","description":"Genomic libraries will be generated from whole genome amplified  genomic DNA derived from 3,000 myeloid neoplasms.  Targeted capture will be performed by multiplexing 16 barcoded samples in each library.  Pools of 96 DNA samples will be subjected to 1-2 lanes of HiSeq 75bp sequencing. Reads will be mapped to the current build of the human reference genome to facilitate the generation of a comprehensive catalog of somatic mutations associated with 116 known myeloid and cancer driver genes.","abstract":"Ongoing sequencing studies are continuously defining new driver genes in myeloid malignancies (Yoshida et al, 2011; Graubert et al, 2012; Ding et al, 2012). Restricted by the availability of large and informative patient cohorts, the diagnostic and prognostic value of these findings is yet to be determined.  In a pathfinding evaluation of the prognostic value of somatic mutation status, Bejar et al analysed mutations in 18 recurrently mutated genes in 438 MDS patients and showed that patients with mutations in TP53, EZH2, ETV6, RUNX1 and ASXL1 were strong predictors of poor outcome (Bejar et al, 2011). A systematic characterisation of all genes known to be mutated in myeloid malignancies as well as some common cancer genes  across a large clinical patient cohort would deliver for the first time a comprehensive understanding of the molecular interplay of somatic mutations in myeloid disease and their individual potential as biomarkers in diagnosis and prognosis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-04-25T14:24:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000276","title":"Genetic_mechanisms_of_resistance_to_chemotherapy_in_breast_cancer","description":"Resistance towards chemotherapy is one of the main causes of treatment failure and deathamong breast cancer patients.The main objective of this project is to identify genetic mechanisms causing some breastcancer patients not to respond to a particluar type of chemotherapy (epirubicin) while otherpatients respond very well to the same treatment.In the project we will perform genome / exome sequencing of a selection of breast cancerpatients (n=30). These patients are drawn from a cohort where all patients have recievedtreatment with epirubicin monotherapy before surgical removal of a locally advanced breasttumour, and where all patients have been subjected to objective evaluation of the response tothe therapy.Subsequent to sequencing, we will analyse the data and compare with the clinical data foreach patient (object response to therapy). The main aim being to identify mutations that areassociated with resistance to epirubicin.Identification of mutations with strong predictive value, may have a direct impact on cancertreatment since it opens the possibility for genetic testing of a tumour, and desicion on whichdrug is likely to work best, prior to treatment start.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-04-26T09:40:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000277","title":"Chondrosarcoma_Targeted_Sequencing_Study","description":"This Study uses a focused bait pull down library method to target findings of Chondrosarcoma whole genome and whole exome sequencing studies in order to validate findings. This method will also be used on a larger set of tumour only samples in order to find precedence of these finding in a larger set of patients.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-17T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000278","title":"Osteosarcoma_Targeted_Sequencing_Study","description":"This Study uses a focused bespoke bait pull down library method to target findings of Osteosarcoma whole genome and whole exome sequencing studies in order to validate findings. This method will also be used on a larger set of tumour only samples in order to find precedence of these findings in a larger set of patient samples.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-05-02T10:02:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000280","title":"Chordoma_Targeted_Sequencing_Study","description":"This Study uses a focused bespoke bait pull down library method to target findings of Chordoma whole genome and whole exome sequencing studies in order to validate findings. This method will also be used on a larger set of tumour only samples in order to find precedence of these findings in a larger set of patient samples.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-05-02T10:14:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000282","title":"Meningioma_Targeted_Sequencing_Study","description":"This Study uses a focused bespoke bait pull down library method to target findings of Meningioma whole genome and whole exome sequencing studies in order to validate findings. This method will also be used on a larger set of tumour only samples in order to find precedence of these findings in a larger set of patient samples.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-05-02T10:18:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000283","title":"RNA_Seq_in_Patients_with_Primordial_Dwarfism","description":"Transcriptome studies in patients with rare genetic diseases can potentially aid in theinterpretation of likely causal genetic variation through identification of altered transcriptabundance and/or structure. RNA-Seq is the most sensitive assay for both investigatingtranscript structure and abundanceThe primary aim of this pilot project is to investigate to what degree integrating exome-Seqand RNA-Seq data on the same individual can accelerate the identification of causal allelesfor rare genetic diseases. There are two main strands to this: (i) identifying which variantsdiscovered in exome-seq appear to be having a functional impact on transcripts, and (ii)identifying transcript outliers, especially among known causal genes, that may not necessarilyhave a causal variant identified from exome sequencing. The latter may identify the presenceof causal variants that lie far from coding regions (e.g. the formation of cryptic splice sitesdeep within introns, or loss of long range regulatory elements), which can be confirmed withfurther targeted genetic assays. Just over 50% of all disease-causing variants recorded in theHuman Gene Mutation Database (HGMD) affect transcript structure and abundance (e.g.nonsense SNVs, essential splice site SNVs, frameshifting indels, CNVs).This pilot project will study RNA from lymphoblastoid cell-lines from 12 patients withprimordial dwarfism syndromes, for 10 of these samples we have previously generate exomedata as part of our collaboration with the group of Prof Andrew Jackson. The two remainingsamples are positive controls where the causal mutation is known, and is known to affecttranscript structure and/or abundance.Primordial dwarfism is a prime candidate for these RNA-seq studies because all knowncausal mutations to date have key roles in DNA replication and thus, unsurprisingly, theproducts of the causal genes are typically ubiquitously expressed.Each RNA will be sequenced, with two technical replicates (independent RT-PCR and libraries) persample, and each replicate run in 1/2 of a HiSeq lane using 100bp paired reads. Samples preparation was as follows :The cells were grown to confluency, then pellets frozen at -80. RNA samples were prepared using the Qiagen RNeasy kit, then nanodropped and analyzed using the bioanalyzer to determine concentration and purity.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Transcriptome studies in patients with rare genetic diseases can potentially aid in theinterpretation of likely causal genetic variation through identification of altered transcriptabundance and/or structure.The primary aim of this pilot project is to investigate to what degree integrating exome-Seqand RNA-Seq data on the same individual can accelerate the identification of causal allelesfor rare genetic diseases.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-05-15T14:22:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000284","title":"BLUEPRINT RNA-seq data for rare cells in the haematopoietic lineages, from adult and cord blood samples.","description":"RNA-seq data for rare cells in the haematopoietic lineages, from adult and cord blood samples.","abstract":"RNA-seq data for rare cells in the haematopoietic lineages, from adult and cord blood samples.","study_type":"Transcriptome Analysis","pubmed_ids":[25258084],"external_links":null,"is_released":true,"released_date":"2012-05-29T16:55:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000285","title":"Validation_of_a_Haloplex_platform_for_targeted_re_sequencing_of_the_exons_of_25_genes","description":"We recently used the Agilent SureSelect platform to re-sequence a set of genes known to bemutated in human AML. The results from 10 AML DNA samples were very satisfactory, butthe effort required was significant.Thus, we decided to re-sequence the same genes using the Haloplax system for targetenrichment in 48 AML samples. We planned to do this using MiSeq and have data from apilot of 3 samples. The data is promising but coverage appears pathcy so far.However, in order to get a better understanding of the data we will need deeper sequencing. Wewill need two lanes of HiSeq to get the same degree coverage as Sureselect.his data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Acute myeloid leukaemia (AML) is an aggressive and molecularly diverse disease with a poor overall survival of 15-25%. With an annual incidence of 2.9 per 100,000, AML is currently the commonest myeloid malignancy in Europe, yet the two main therapeutic options for this disease, anthracyclines and purine analogues, have remained unchanged for over 20 years. A number of novel mutations have been identified in AML and many have prognostic and therapeutic implications. This study aims to validate a tool for simultaneous identification of these mutations in individual AML samples, which can be used to guide patient treatment decisions.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-05-30T12:05:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000286","title":"APCDR AGV Project: WGS of South African Zulu","description":"The African Genome Variation Project (AGVP) provides a resource to help design, implement and interpret genomic studies in sub-Saharan Africa (SSA) and worldwide. The AGVP represents dense genotypes from 1,481 and whole genome sequences (WGS) from 320 individuals across SSA. \nAs part of the AGVP we sequenced the genome of 100 unrelated Zulu from Durban area to about 4x depth.","abstract":"The African Genome Variation Project (AGVP) provides a resource to help design, implement and interpret genomic studies in sub-Saharan Africa (SSA) and worldwide. The AGVP represents dense genotypes from 1,481 and whole genome sequences (WGS) from 320 individuals across SSA. \nAs part of the AGVP we sequenced the genome of 100 unrelated Zulu from Durban area to about 4x depth.","study_type":"Other","pubmed_ids":[25470054],"external_links":null,"is_released":true,"released_date":"2012-05-30T14:51:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000287","title":"Diagnostic Exome Sequencing in Persons with Severe Intellectual Disability","description":"Intellectual disability is a common condition that carries lifelong severe medical and developmental consequences. The causes of intellectual disability (ID) remain unknown for the majority of patients due to the extensive clinical and genetic heterogeneity of this disorder. De novo mutations may play an important role in ID as most individuals with ID present as isolated cases without family history and/or clear syndromic indication. In addition, the involvement of such mutations have recently been demonstrated in a small number of individuals with ID. Here we evaluate the diagnostic potential and role of de novo mutations in a cohort of 100 patients with ID of unknown cause using family-based exome sequencing.","abstract":"Intellectual disability is a common condition that carries lifelong severe medical and developmental consequences. The causes of intellectual disability (ID) remain unknown for the majority of patients due to the extensive clinical and genetic heterogeneity of this disorder. De novo mutations may play an important role in ID as most individuals with ID present as isolated cases without family history and/or clear syndromic indication. In addition, the involvement of such mutations have recently been demonstrated in a small number of individuals with ID. Here we evaluate the diagnostic potential and role of de novo mutations in a cohort of 100 patients with ID of unknown cause using family-based exome sequencing.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-05-30T16:26:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000288","title":"Genentech Colon Cancer Screen","description":"Identifying and understanding changes in cancer genomes is essential for the development of targeted therapeutics. Here we analyse systematically more than 70 pairs of primary human colon tumours by applying next-generation sequencing to characterize their exomes, transcriptomes and copy-number alterations. We have identified 36,303 protein-altering somatic changes that include several new recurrent mutations in the Wnt pathway gene TCF7L2, chromatin-remodelling genes such as TET2 and TET3 and receptor tyrosine kinases including ERBB3. Our analysis for significantly mutated cancer genes identified 23 candidates, including the cell cycle checkpoint kinase ATM. Copy-number and RNA-seq data analysis identified amplifications and corresponding overexpression of IGF2 in a subset of colon tumours. Furthermore, using RNA-seq data we identified multiple fusion transcripts including recurrent gene fusions involving R-spondin family members RSPO2 and RSPO3 that together occur in 10% of colon tumours. The RSPO fusions were mutually exclusive with APC mutations, indicating that they probably have a role in the activation of Wnt signalling and tumorigenesis. Consistent with this we show that the RSPO fusion proteins were capable of potentiating Wnt signalling. The R-spondin gene fusions and several other gene mutations identified in this study provide new potential opportunities for therapeutic intervention in colon cancer.","abstract":"Identifying and understanding changes in cancer genomes is essential for the development of targeted therapeutics. Here we analyse systematically more than 70 pairs of primary human colon tumours by applying next-generation sequencing to characterize their exomes, transcriptomes and copy-number alterations. We have identified 36,303 protein-altering somatic changes that include several new recurrent mutations in the Wnt pathway gene TCF7L2, chromatin-remodelling genes such as TET2 and TET3 and receptor tyrosine kinases including ERBB3. Our analysis for significantly mutated cancer genes identified 23 candidates, including the cell cycle checkpoint kinase ATM. Copy-number and RNA-seq data analysis identified amplifications and corresponding overexpression of IGF2 in a subset of colon tumours. Furthermore, using RNA-seq data we identified multiple fusion transcripts including recurrent gene fusions involving R-spondin family members RSPO2 and RSPO3 that together occur in 10% of colon tumours. The RSPO fusions were mutually exclusive with APC mutations, indicating that they probably have a role in the activation of Wnt signalling and tumorigenesis. Consistent with this we show that the RSPO fusion proteins were capable of potentiating Wnt signalling. The R-spondin gene fusions and several other gene mutations identified in this study provide new potential opportunities for therapeutic intervention in colon cancer.","study_type":"Cancer Genomics","pubmed_ids":[22895193],"external_links":null,"is_released":true,"released_date":"2012-05-31T17:15:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000289","title":"Lung_Plasma_rearrangement_screen","description":"Genomic libraries (500 bps) will be generated from total genomic DNA derived from lung cancer patients and subjected to short paired end sequencing on the llumina platform. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemias, lymphomas and soft tissue tumors. However, conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution. We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-06-08T10:13:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000290","title":"Myeloproliferative_Disease_Whole_Genomes","description":"Wholegenome libraries will be prepared from at least two serial samples reflecting different stages of disease progression and matched constitutional DNA for 30 Myeloproliferative Disease samples. Five lanes of Illumina HiSeq sequencing will be performed on each of the tumour samples and four lanes for each of the constitutional DNA. Sequencing data will mapped to build 37 of the human reference genome and analysis will be performed to characterize the spectrum of somatic variation present in these samples including single base pair mutations, insertions, deletions as well as larger structural variants and genomic rearrangements.","abstract":"Cancer is driven by mutation and is typically highly heterogeneous with each tumour represented by multiple subclonal compartments each with its unique spectrum of mutation clusters. Using whole genome library preparation and massively parallel sequencing technology, we aim to the entire genome of 30 pairs of Myeloproliferative disease samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with Myeloproliferative disease development and disease progression.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-06-08T11:15:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000291","title":"Myelodysplastic_syndrome_whole_genomes","description":"Wholegenome libraries will be prepared from at least two serial samples reflecting different stages of disease progression and matched constitutional DNA for 30 Myelodysplastic syndrome patient samples. Five lanes of Illumina HiSeq sequencing will be performed on each of the tumour samples and four lanes for each of the constitutional DNA. Sequencing data will mapped to build 37 of the human reference genome and analysis will be performed to characterize the spectrum of somatic variation present in these samples including single base pair mutations, insertions, deletions as well as larger structural variants and genomic rearrangements.","abstract":"Cancer is driven by mutation and is typically highly heterogeneous with each tumour represented by multiple subclonal compartments each with its unique spectrum of mutation clusters. Using whole genome library preparation and massively parallel sequencing technology, we aim to the entire genome of 30 paired Myelodysplastic syndrome samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with Myelodysplasia development and disease progression.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-06-08T11:16:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000292","title":"Molecular_characterization_of_invasive_lobular_carcinoma","description":"Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer accounting for 10-15% of cases. ILC differs from invasive ductal carcinoma (IDC)with respect to epidemiology, histology, and clinical presentation. Moreover, ILC is lesssensitive to chemotherapy, more frequently bilateral, and more prone to form gastrointestinal, peritoneal, and ovarian metastases than IDCs. In contrast to IDC, the prognostic value ofhistological grade (HG) in ILC is controversial. One of the three major components of histological grading (tubule formation) is missing in ILC which hinders the process of gradingin this histological subtype and results in the classification of approximately two thirds of ILC as HG 2.Over the last decade, a number of gene expression signatures have shed light onto breast cancer classification, allowing breast cancer care to become more personalized. Withrespect to the management of estrogen receptor (ER)-positive breast cancer, several gene expression signatures provide prognostic and/or predictive information beyond what is possible with current classical clinico-pathological parameters alone. Nevertheless, most studies using gene expression signature have not considered different histologic subtypesseparately. Recently, a comprehensive research program has elucidated some of the biological underpinnings of invasive lobular carcinoma. Genetic material extracted from 200 ILC tumor samples were studied using gene expression profiling and identified ILCmolecular subtypes. These proliferation-driven gene signatures of ILC appear to have prognostic significance. In particular, the Genomic Grade (GG) gene signature improved upon HG in ILC and added prognostic value to classic clinico-pathologic factors. In addition this study demonstrated that most ILC are molecularly characterized as luminal-A (~75%)followed by luminal-B (~20%) and HER2-positve tumors (~5%). Moreover, we investigated the prognostic value of known gene signatures/ gene modules in the same cohort of ILC. As a second step within the scope of this project, we aim to investigate the interactionsbetween somatic ILC tumor mutations to observed transcriptome findings. To this end, we aim to perform somatic mutation analysis for the ILC tumors for which Affymetrix gene expression profiling is available. To this end, we will use a gene screen assay, which specifically interrogates the mutational status of a few hundreds of cancer genes. We believe that this pioneering effort will be fundamental for a tailored treatment of ILC withimprovement in patients' outcome.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-06-15T16:40:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000293","title":"Evaluation_of_size_selection_on_cancer_specific_sequencing_libraries","description":"A couple of previously characterized and sequenced libraries will be repeated using a couple of differing size selection criteria and skim sequenced using an Illumina HiSeq. The resulting sequence will be analyzed to determine the optimal DNA library size for our specific downstream analysis.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. In order to maintain these aims to the best of our abilities we must continually assess best practice.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-06-15T16:58:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000295","title":"Gene_Discovery_in_Age_Related_Hearing_Loss","description":"The aim is to find new candidate genes associated with progressive hearing loss","abstract":"DNA samples have been collected systematically from adults attending an audiology clinic for advice about their progressive hearing loss.  The clinic has detailed audiometry data available and subsets have been selected on the basis of the exact pattern of their hearing loss.  These subsets will be used for whole exome resequencing in order to discover new candidate genes associated with progressive hearing loss.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-06-18T09:03:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000296","title":"Exome sequencing identifies mutation of the ribosome in T-cell acute lymphoblastic leukemia","description":"Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and responds well to therapy in children, but not in adults. We used exome sequencing of 67 T-cell ALL (T- ALL) samples to gain insight in the mutational spectrum and age related differences of these leukemias. We detected protein-altering mutations in 508 genes, with an average of 8.2 mutations in pediatric and 21.0 in adult T-ALL. Based on stringent filtering, we predict 15 of these genes to be drivers, including 7 genes that were not previously implicated in T-ALL. We identify CNOT3 as a new tumor suppressor, as it is mutated in 12.2 % of adult T-ALLs and its knock-down causes de novo tumors in a sensitized drosophila eye tumor model. In addition, we identify mutations in RPL5 and RPL10, proteins of the 60S ribosomal complex2, in 18.2 % of pediatric T-ALLs. Mutation of arginine 98 in the X-linked RPL10 gene was most frequent. Yeast cells expressing the Rpl10 R98S mutant showed a clear ribosome biogenesis defect, excluding that this mutation is a passenger mutation. Our data provide insights in the mutational landscape of pediatric and adult T-ALL and identify the ribosome as a potential oncogenic factor in cancer.","abstract":"Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and responds well to therapy in children, but not in adults. We used exome sequencing of 67 T-cell ALL (T- ALL) samples to gain insight in the mutational spectrum and age related differences of these leukemias. We detected protein-altering mutations in 508 genes, with an average of 8.2 mutations in pediatric and 21.0 in adult T-ALL. Based on stringent filtering, we predict 15 of these genes to be drivers, including 7 genes that were not previously implicated in T-ALL. We identify CNOT3 as a new tumor suppressor, as it is mutated in 12.2 % of adult T-ALLs and its knock-down causes de novo tumors in a sensitized drosophila eye tumor model. In addition, we identify mutations in RPL5 and RPL10, proteins of the 60S ribosomal complex2, in 18.2 % of pediatric T-ALLs. Mutation of arginine 98 in the X-linked RPL10 gene was most frequent. Yeast cells expressing the Rpl10 R98S mutant showed a clear ribosome biogenesis defect, excluding that this mutation is a passenger mutation. Our data provide insights in the mutational landscape of pediatric and adult T-ALL and identify the ribosome as a potential oncogenic factor in cancer.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-06-18T10:09:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000297","title":"Feasibility_of_targeted_capture_sequencing_in_routinely_collected_FFPE_cancer_specimens","description":"Testing the feasibility of genome-scale sequencing in routinely collected formalin-fixed paraffin-embedded (FFPE) cancer specimens versus matched fresh-frozen samples using targeted pulldown capture prior to Illumina sequencing.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale. Being able to follow up studies in a larger cohort from FFPE samples would greatly increase the capacity of these studies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-06-18T16:08:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000298","title":"The title gets updated ","description":" I am updating the abstract THIS IS A TEST SUBMISSION - GARY EDIT","abstract":" I am updating the abstract THIS IS A TEST SUBMISSION - GARY EDIT","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000299","title":"Integrative analysis of small cell lung cancer","description":"Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype. We conducted integrated analysis of genome sequencing, transcriptome, and copy number analysis and found an extremely high mutation rate of 7.4±1 protein-changing mutations per million basepairs. Evidence for inactivation of TP53 and RB1 was found in all sequenced cases. Furthermore, we identified recurrent mutations in CREBBP, EP300, and MLL, observed mutations in PTEN, in SLIT2, and EPHA7, as well as focal amplifications of the FGFR1 locus. As a major feature of SCLC we found mutation in histone modifying genes, observed genome alterations that are therapeutically tractable, and provide a framework for identifying biologically relevant genes in the context of a high mutation rate. Peifer et al., 2012, Nature Genetics.","abstract":"Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype. We conducted integrated analysis of genome sequencing, transcriptome, and copy number analysis and found an extremely high mutation rate of 7.4±1 protein-changing mutations per million basepairs. Evidence for inactivation of TP53 and RB1 was found in all sequenced cases. Furthermore, we identified recurrent mutations in CREBBP, EP300, and MLL, observed mutations in PTEN, in SLIT2, and EPHA7, as well as focal amplifications of the FGFR1 locus. As a major feature of SCLC we found mutation in histone modifying genes, observed genome alterations that are therapeutically tractable, and provide a framework for identifying biologically relevant genes in the context of a high mutation rate. Peifer et al., 2012, Nature Genetics.","study_type":"Other","pubmed_ids":[22941188],"external_links":null,"is_released":true,"released_date":"2012-06-20T17:01:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000300","title":"Breast_cancer_sequential_sampling_study","description":"This study aims to whole genome sequence DNA derived from breast cancer patients who received neo-adjuvany chemotherapy. All patients had multiple biopsies performed before chemotherapy. Patients who had residual disease after the course of treatment underwent a further biopsy. We aim to characterise the mutations involved.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-06-21T09:57:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000301","title":"Cancer_Genome_Project_Exome_Sequencing","description":"Agilent whole exome hybridisation capture was performed on genomic DNA derived from cancer and matched normal DNA from the same patients. Next Generation sequencing performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes. Now we aim to re find and validate the findings of those exome libraries using bespoke pulldown methods and sequencing the products.","abstract":"Cancer is driven by mutation. Illumina massively parallel sequencing technology will be applied to Agilent exome hybridisation capture libraries and total genomic paired-end libraries from a range of cancer samples. Bespoke algorithms are being developed to identify the somatically acquired structural variants, point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-06-21T16:20:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000304","title":"Replication_of_candidate_causal_genes_for_Tetralogy_of_Fallot","description":"This project is a custom targeted resequencing replication study following up on candidate genes identified from exome sequencing of 30 parent-offspring trios where the child has a specific sporadic congenital heart defect, Tetralogy of Fallot (TOF), in addition to candidate genes from other sources, including: genes in de novo CNVs, strong functional candidates, and genes for other congenital heart defects. The aim is to identify additional families with likely causal mutations in these candidate genes. We will design a custom pulldown library targeting ~0.5Mb of sequence (~300 genes) and sequence 256 parent-offspring trios (2x 384 well plates). This sample size is determined from a consideration of how likely it is to observe recurrent de novo LOF mutations given the average length of coding sequence, the germline mutation rate and the likely fraction of new mutations that are LOF, and the prevalence of TOF, as well as the practical advantages of processing an integer multiple of 384 samples.","abstract":"This project is a custom targeted resequencing replication study following up on candidate genes identified from exome sequencing of 30 parent-offspring trios where the child has a specific sporadic congenital heart defect, Tetralogy of Fallot (TOF), in addition to candidate genes from other sources, including: genes in de novo CNVs, strong functional candidates, and genes for other congenital heart defects. The aim is to identify additional families with likely causal mutations in these candidate genes. We will design a custom pulldown library targeting ~0.5Mb of sequence (~300 genes) and sequence 256 parent-offspring trios (2x 384 well plates).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000305","title":"P647_Targeted_resequencing_project","description":"In collaboration with Dr Robert Semple we have identified a family harbouring an autosomal dominant variant, which leads to severe insulin resistance (SIR), short stature and facial dysmorphism. This family is unique within the SIR cohort in having normal lipid profiles, preserved adiponectin and normal INSR expression and phosphorylation. DNA is available for 7 affected and 7 unaffected family members across 3 generations. All 14 samples have been genotyped using microsatellites and the Affymetrix 6.0 SNP chip. Linkage analysis identified an 18.8Mb haplotype on chromosome 19 as a possible location of the causative variant. However, Exome sequencing of 3 affected and 1 unaffected family members has not identified the causative variant suggesting the possibility of an intronic or intergenic variant in this region or elsewhere in the genome. We propose to conduct whole genome sequencing of 5 members of the pedigree at a depth of 20X. The chosen samples are two sets of parents plus one member of an unaffected branch of the pedigree who shares the risk haplotype on chromosome 19. Sequencing of the two sets of parents will be used along with the genome-wide SNP data to impute 4 affected children giving an effect sample size of 6 affected individuals.","abstract":"In collaboration with Dr Robert Semple we have identified a family harbouring an autosomal dominant variant, which leads to severe insulin resistance (SIR), short stature and facial dysmorphism. This family is unique within the SIR cohort in having normal lipid profiles, preserved adiponectin and normal INSR expression and phosphorylation. DNA is available for 7 affected and 7 unaffected family members across 3 generations. All 14 samples have been genotyped using microsatellites and the Affymetrix 6.0 SNP chip. Linkage analysis identified an 18.8Mb haplotype on chromosome 19 as a possible location of the causative variant. However, Exome sequencing of 3 affected and 1 unaffected family members has not identified the causative variant suggesting the possibility of an intronic or intergenic variant in this region or elsewhere in the genome. We propose to conduct whole genome sequencing of 5 members of the pedigree at a depth of 20X. The chosen samples are two sets of parents plus one member of an unaffected branch of the pedigree who shares the risk haplotype on chromosome 19. Sequencing of the two sets of parents will be used along with the genome-wide SNP data to impute 4 affected children giving an effect sample size of 6 affected individuals.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-06-26T11:56:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000306","title":"UK10K OBESITY TWINSUK","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. These TwinsUK samples are a subset of the TwinsUK cohort samples with a BMI&gt;=40 that will be exome sequenced by the Obesity group.","abstract":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. These TwinsUK samples are a subset of the TwinsUK cohort samples with a BMI&gt;=40 that will be exome sequenced by the Obesity group.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-06-26T16:43:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000307","title":"UK10K_exome_sequence__ALSPAC_samples","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. These ALSPAC samples are a subset of the ALSPAC cohort samples with a BMI&gt;=40 that will be exome sequenced by the Obesity group.","abstract":"The Avon Longitudinal Study of Parents and Children (ALSPAC) is a two-generation prospective study. Pregnant women living in one of three health districts in the former county of Avon with an expected delivery date between April 1991 and December 1992 were eligible to be enrolled in the study, and this formed the intitial point of contact for the development of a large, family based resource.Detailed information has been collected on the children and the mothers through retrieval of biological materials (e.g. antenatal blood samples, placentas), biological sampling (e.g. collection of cord blood, umbilical cord, milk teeth, hair, toenails, blood and urine), self-administered questionnaires, data extraction from medical notes, linkage to routine information systems and at repeat research clinics.A subset of the ALSPAC samples with BMI&gt;=40 will undergo exome sequencing as part of the Obesity arm of the UK10K project.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000308","title":"Targeted_sequencing_of_candidate_genes_in_calcific_aortic_valve_stenosis","description":"The objective is to identify new disease genes involved in calcific aortic valve stenosis (CAVS) by screening newly identified candidate genes. The recruitment of patients with CAVS has been achieved by l’institut du thorax (Nantes, France). DNA from the selected patients has been analysed by targeted capture (Agilent SureSelect) and massively parallel sequencing (Illumina).","abstract":"Calcific aortic valve stenosis (CAVS) is the most frequent heart valve disease, but despite its high incidence in the ageing population, pathophysiologic mechanisms are unknown and the only therapy is surgical valve replacement. The aim of this project is to identify new genes associated with the disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-06-27T09:10:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000309","title":"ddd","description":"ddd","abstract":"ddd","study_type":"Synthetic Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000310","title":"RNA_sequencing","description":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale. NB bam files for manuscript A_Proteomic_Chronology_of_Gene_Expression_through_the_Cell_Cycle_in_Human_Myeloid_Leukemia_Cells are now available at the following link:http://www.ebi.ac.uk/ena/data/view/ERP008483","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale. NB bam files for manuscript A_Proteomic_Chronology_of_Gene_Expression_through_the_Cell_Cycle_in_Human_Myeloid_Leukemia_Cells are now available at the following link:http://www.ebi.ac.uk/ena/data/view/ERP008483","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-06-28T16:29:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000311","title":"Genomic_stability_of_induced_pluripotent_stem_cells_derived_from_twin_individuals","description":"Fibroblasts from a small number of MZ and DZ pairs from the TwinsUK registry are used to generate  induced pluripotent stem cells (iPS) cells using two different protocols (SHIPS method by Pentao Liu and hIPSCs method developed by Yamanka and used in Ludovic Vallier lab, Cambridge University). Skin biopsies have been obtained from 8 individuals and primary fibroblasts from six of them have been succefully used  to generate hIPSC lines (2 clones per individual) - SHIPS have been generated from 2 individuals.  We are looking at the chromatin architecture of the generated iPS lines and parental fibroblast lines by profiling chromatin for signatures of nucleosome depleted regions (NDRs) with the FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) assay and signatures of regulatory elements with chromatin immunoprecipitation (ChIP) - H3K4me1, H3K27ac and H3K27me3.  The genomic stability between iPS clones per protocol and across protocols for a given individual will be investigated using Whole genome sequencing.","abstract":"Fibroblasts from a small number of MZ and DZ pairs from the TwinsUK registry are used to generate  induced pluripotent stem cells (iPS) cells using two different protocols (SHIPS method by Pentao Liu and hIPSCs method developed by Yamanka and used in Ludovic Vallier lab, Cambridge University). Skin biopsies have been obtained from 8 individuals and primary fibroblasts from six of them have been succefully used  to generate hIPSC lines (2 clones per individual) - SHIPS have been generated from 2 individuals.  We are looking at the chromatin architecture of the generated iPS lines and parental fibroblast lines by profiling chromatin for signatures of nucleosome depleted regions (NDRs) with the FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) assay and signatures of regulatory elements with chromatin immunoprecipitation (ChIP) - H3K4me1, H3K27ac and H3K27me3.  The genomic stability between iPS clones per protocol and across protocols for a given individual will be investigated using Whole genome sequencing.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000312","title":"a whole genome sequencing (WGS) study of 88 matched HCC tumour/normal pairs","description":"This study to identify genetically altered genes and pathways implicated in HBV-associated HCC","abstract":"This study to identify genetically altered genes and pathways implicated in HBV-associated HCC","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000313","title":"Human_Evolution_3","description":"The mtDNA and Y chromosome of up to 15 Australian Aborigines,  concentrating on individuals with indigenous lineages, will be sequenced using the standard whole-genome sequencing followed by filtering out of autosomal and X sequences, so that only mtDNA and the Y chromosome will be analysed and released.","abstract":"According to current models of human expansion out of Africa around 60,000 years ago, there was an early divergence between the ancestors of Australian Aborigines on the one hand and the ancestors of Asians, Europeans and most other non-Africans on the other. Australian Aborigines are therefore of particular importance for understanding these early events, and the subsequent history of this branch of humanity. The project will sequence the mtDNA and Y chromosome of up to 15 Australian Aborigines,  concentrating on individuals with indigenous lineages, to address these questions.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000314","title":"Human_Evolution_3","description":"The mtDNA and Y chromosome of up to 15 Australian Aborigines,  concentrating on individuals with indigenous lineages, will be sequenced using the standard whole-genome sequencing followed by filtering out of autosomal and X sequences, so that only mtDNA and the Y chromosome will be analysed and released.","abstract":"According to current models of human expansion out of Africa around 60,000 years ago, there was an early divergence between the ancestors of Australian Aborigines on the one hand and the ancestors of Asians, Europeans and most other non-Africans on the other. Australian Aborigines are therefore of particular importance for understanding these early events, and the subsequent history of this branch of humanity. The project will sequence the mtDNA and Y chromosome of up to 15 Australian Aborigines,  concentrating on individuals with indigenous lineages, to address these questions.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000315","title":"Human_Evolution_3","description":"The mtDNA and Y chromosome of up to 15 Australian Aborigines,  concentrating on individuals with indigenous lineages, will be sequenced using the standard whole-genome sequencing followed by filtering out of autosomal and X sequences, so that only mtDNA and the Y chromosome will be analysed and released.","abstract":"According to current models of human expansion out of Africa around 60,000 years ago, there was an early divergence between the ancestors of Australian Aborigines on the one hand and the ancestors of Asians, Europeans and most other non-Africans on the other. Australian Aborigines are therefore of particular importance for understanding these early events, and the subsequent history of this branch of humanity. The project will sequence the mtDNA and Y chromosome of up to 15 Australian Aborigines,  concentrating on individuals with indigenous lineages, to address these questions.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-07-10T16:43:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000316","title":"Kuusamo_whole_exome_sequencing","description":"Whole exome sequencing of samples selected from the Finrisk sample collection. The samples sequenced in this study have all been collected in Kuusamo, Finland.","abstract":"Whole exome sequencing of samples selected from the Finrisk sample collection. The samples sequenced in this study have all been collected in Kuusamo, Finland.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000317","title":"Exome_sequencing_of_Congenital_Heart_Disease_families_Toronto","description":"Atrio-ventricular septal defects (AVSD) are a specific form of congenital heart structural defect that result from abnormal or inadequate fusion of endocardial cushions during cardiac development. This project is focused on identifying rare coding variation that substantially increases risk of AVSD, by exome sequencing of AVSD patients and some of their family members, and comparing to control datasets from other sources.","abstract":"Atrio-ventricular septal defects (AVSD) are a specific form of congenital heart structural defect that result from abnormal or inadequate fusion of endocardial cushions during cardiac development. This project is focused on identifying rare coding variation that substantially increases risk of AVSD, by exome sequencing of AVSD patients and some of their family members, and comparing to control datasets from other sources.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-07-17T08:19:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000318","title":"Whole-exome Sequencing Combined with Functional Genomics Reveals Novel Candidate Driver Cancer Genes in Endometrial Cancer","description":"Endometrial cancer is the most common gynecological malignancy, with more than 280,000 cases occurring annually worldwide. Although previous studies have identified important common somatic mutations in endometrial cancer, they have primarily focused on a small set of known cancer genes and have thus provided a limited view of the molecular basis underlying this disease. Here we developed an integrated systems biology approach to identifying novel cancer genes contributing to endometrial tumorigenesis. We first performed whole-exome sequencing on 13 endometrial cancers and matched normal samples, systematically identifying somatic alterations with high precision and sensitivity. We then combined bioinformatics prioritization with high-throughput screening (including both shRNA-mediated knockdown and expression of wild type and mutant constructs) in a highly sensitive cell viability assay. Our results revealed 12 potential driver cancer genes including 10 tumor suppressor candidates (ARID1A, INHBA, KMO, TTLL5, GRM8, IGFBP3, AKTIP, PHKA2, TRPS1 and WNT11) and two oncogene candidates (ERBB3 and RPS6KC1). The results in the “sensor” cell line were recapitulated by siRNA-mediated knockdown in endometrial cancer cell lines. Focusing on ARID1A, we integrated mutation profiles with functional proteomics in 222 endometrial cancer samples, demonstrating that ARID1A mutations frequently co-occur with mutations in the phosphatidylinositol 3-kinase (PI3K) pathway and are associated with PI3K pathway activation. siRNA knockdown in endometrial cancer cell lines increased AKT phosphorylation supporting ARID1A as a novel regulator of PI3K pathway activity. Our study presents the first unbiased view of somatic coding mutations in endometrial cancer and provides functional evidence for diverse driver genes and mutations in this disease.","abstract":"Endometrial cancer is the most common gynecological malignancy, with more than 280,000 cases occurring annually worldwide. Although previous studies have identified important common somatic mutations in endometrial cancer, they have primarily focused on a small set of known cancer genes and have thus provided a limited view of the molecular basis underlying this disease. Here we developed an integrated systems biology approach to identifying novel cancer genes contributing to endometrial tumorigenesis. We first performed whole-exome sequencing on 13 endometrial cancers and matched normal samples, systematically identifying somatic alterations with high precision and sensitivity. We then combined bioinformatics prioritization with high-throughput screening (including both shRNA-mediated knockdown and expression of wild type and mutant constructs) in a highly sensitive cell viability assay. Our results revealed 12 potential driver cancer genes including 10 tumor suppressor candidates (ARID1A, INHBA, KMO, TTLL5, GRM8, IGFBP3, AKTIP, PHKA2, TRPS1 and WNT11) and two oncogene candidates (ERBB3 and RPS6KC1). The results in the “sensor” cell line were recapitulated by siRNA-mediated knockdown in endometrial cancer cell lines. Focusing on ARID1A, we integrated mutation profiles with functional proteomics in 222 endometrial cancer samples, demonstrating that ARID1A mutations frequently co-occur with mutations in the phosphatidylinositol 3-kinase (PI3K) pathway and are associated with PI3K pathway activation. siRNA knockdown in endometrial cancer cell lines increased AKT phosphorylation supporting ARID1A as a novel regulator of PI3K pathway activity. Our study presents the first unbiased view of somatic coding mutations in endometrial cancer and provides functional evidence for diverse driver genes and mutations in this disease.","study_type":"Exome Sequencing","pubmed_ids":[23028188],"external_links":null,"is_released":true,"released_date":"2012-07-17T21:28:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000319","title":"UK10K_whole_genome_sequence__Raymond_samples","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The Raymond samples will be part of the “rare disease” group, and will undergo whole genome sequencing.","abstract":"The Raymond group sample set are all from families with moderate to severe intellectual disability. They are mostly at the severe end of the spectrum and have been seen by a clinical geneticist where no known diagnosis has been made. The majority are familial cases with a range of inheritance patterns including multigenerational and single generation families where there are at least 2 affected individuals but a few aresingletons where the disease is severe. The families are largely Caucasian and non consanguineous.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000320","title":"UK10K_whole_genome_sequence__Ciliopathies","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing.  We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The Ciliopathies samples will be part of the “rare disease” group, and will undergo whole genome sequencing.","abstract":"The ciliopathies are an emerging group of disorders that arise from some dysfunction of cilia albeit motile or immotile forms. There are predicted to exist over 100 known conditions likely to fall under this category but only a handful have thus far been studied in any depth. Most individual ciliopathies are rare with just a handful of cases having been reported thereby presenting researchers with often insurmountable difficulties for causative gene identification.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000321","title":"UK10K_whole_genome_sequence__Neuromuscular_samples","description":"In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The neuromuscular disorder samples are part of the “rare disease” group, and will undergo whole genome sequencing.","abstract":"The Rare Neuromuscular Disorders cohort consists of 4 different neuromuscular disease categories: 1. congenital muscular dystrophies and congenital myopathies, 2. neurogenic conditions, 3. mitochondrial disorders, and 4. periodic paralysis. For specific conditions we have expertise in functional experimental procedures. This set is a very wellphenotyped and a relatively unique collection of patients.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000322","title":"De_novo_mutations_in_cell_free_foetal_DNA__cffDNA_","description":"This project is to develop and validate a method to detect de novo mutations in a foetal genome through deep sequencing of cell-free DNA from the plasma of pregnant women.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This project is to develop and validate a method to detect de novo mutations in a foetal genome through deep sequencing of cell-free DNA from the plasma of a pregnant women. Approximately 10-15% of this cell-free DNA is from the foetus. By  sequencing the maternal plasma very deeply and adapting our current  de novo mutation calling algorithms we hope to demonstrate that de novo mutations can be reliably detected in this manner. We have modelled the dependence of the performance of de novo mutation detection on sequencing coverage and have conservatively estimated that  the maternal plasma DNA ought to be sequenced to 200X coverage. To achieve this coverage with the limited amount of cell-free DNA in maternal plasma requires a very high yield library preparation protocol for sufficient library complexity to support deep sequencing. Mike Quail has been developing such a protocol using limited amounts of genomic DNA. To validate our approach we require a catalogue of validated de novo mutations (positive controls) in a parent-offspring trio for which maternal, paternal and maternal plasma DNA are available. To generate this catalogue of de novo mutations in the first place, in addition to the maternal and paternal DNA, we also require foetal DNA, from CVS or amniocentesis.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-07-19T10:12:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000323","title":"Identifying genetic consequences of Epstein-Barr Virus transformation by comparing an individual’s genomic DNA with that of its lymphoblastoid cell line.","description":"A detailed analysis of whole genomes can be now achieved with next generation sequencing. Epstein Barr Virus (EBV) transformation is a widely used strategy in clinical research to obtain an unlimited source of a subject’s DNA. Although the mechanism of transformation and immortalization by EBV is relatively well known at the transcriptional and proteomic level, the genetic consequences of EBV transformation are less well understood. A detailed analysis of the genetic alterations introduced by EBV transformation is highly relevant, as it will inform on the usefulness and limitations of this approach. We used whole genome sequencing to assess the genomic signature of a low-passage lymphoblastoid cell line (LCL). Specifically, we sequenced the full genome (40X) of an individual using DNA purified from fresh whole blood as well as DNA from his LCL. A total of 217.33 Gb of sequence were generated from the cell line and 238.95 Gb from the normal genomic DNA. We determined with high confidence that 99.2% of the genomes were identical, with no reproducible changes in structural variation (chromosomal rearrangements and copy number variations) or insertion/deletion polymorphisms (indels). Our results suggest that, at this level of resolution, the LCL is genetically indistinguishable from its genomic counterpart and therefore their use in clinical research is not likely to introduce a significant bias.","abstract":"A detailed analysis of whole genomes can be now achieved with next generation sequencing. Epstein Barr Virus (EBV) transformation is a widely used strategy in clinical research to obtain an unlimited source of a subject’s DNA. Although the mechanism of transformation and immortalization by EBV is relatively well known at the transcriptional and proteomic level, the genetic consequences of EBV transformation are less well understood. A detailed analysis of the genetic alterations introduced by EBV transformation is highly relevant, as it will inform on the usefulness and limitations of this approach. We used whole genome sequencing to assess the genomic signature of a low-passage lymphoblastoid cell line (LCL). Specifically, we sequenced the full genome (40X) of an individual using DNA purified from fresh whole blood as well as DNA from his LCL. A total of 217.33 Gb of sequence were generated from the cell line and 238.95 Gb from the normal genomic DNA. We determined with high confidence that 99.2% of the genomes were identical, with no reproducible changes in structural variation (chromosomal rearrangements and copy number variations) or insertion/deletion polymorphisms (indels). Our results suggest that, at this level of resolution, the LCL is genetically indistinguishable from its genomic counterpart and therefore their use in clinical research is not likely to introduce a significant bias.","study_type":"Whole Genome Sequencing","pubmed_ids":[22974163],"external_links":null,"is_released":true,"released_date":"2012-07-19T20:03:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000324","title":"The map of variability of human microRNAs","description":"MicroRNAs (miRNAs) are key components of the gene regulatory network in a wide range of species. During the last years these regulatory elements have been involved in an increasing range of diseases. Consequently, the availability of a comprehensive compilation of the map of natural variability in healthy population seems an obvious requirement for future research on miRNA-related pathologies. The analysis of the data available on 14 populations of the 1000 genomes project, supplemented with data extracted from 60 new exomes of healthy individuals from a southern Spain population, sequenced in the context of the Medical Genome Project, has allowed us to derive an accurate map of miRNA variability. Despite the common belief that miRNAs are highly conserved elements, the observation based on the sequences of 1152 individuals analysed indicates that the amount of variability doubles what it was previously expected. A total of 527 variants were found. Among these, 44 variants affected the recognition region of the corresponding miRNA and were found in 43 different miRNAs, 26 of which are known to be involved in almost 57 diseases. Different parts of the mature structure of the microRNA were affected at different degrees by variants, which suggest the existence of a selective pressure that depends on the relative functional impact of the change. Moreover, 41 variants show a significant deviation from the Hardy-Weinberg equilibrium, which supports the existence of a selective process against some alleles. The average number of variants per individual found in miRNAs was of 28. Despite miRNAs were thought to be a highly conserved genomic element, our study reports a level of variability comparable to what it was observed for coding genes.","abstract":"MicroRNAs (miRNAs) are key components of the gene regulatory network in a wide range of species. During the last years these regulatory elements have been involved in an increasing range of diseases. Consequently, the availability of a comprehensive compilation of the map of natural variability in healthy population seems an obvious requirement for future research on miRNA-related pathologies. The analysis of the data available on 14 populations of the 1000 genomes project, supplemented with data extracted from 60 new exomes of healthy individuals from a southern Spain population, sequenced in the context of the Medical Genome Project, has allowed us to derive an accurate map of miRNA variability. Despite the common belief that miRNAs are highly conserved elements, the observation based on the sequences of 1152 individuals analysed indicates that the amount of variability doubles what it was previously expected. A total of 527 variants were found. Among these, 44 variants affected the recognition region of the corresponding miRNA and were found in 43 different miRNAs, 26 of which are known to be involved in almost 57 diseases. Different parts of the mature structure of the microRNA were affected at different degrees by variants, which suggest the existence of a selective pressure that depends on the relative functional impact of the change. Moreover, 41 variants show a significant deviation from the Hardy-Weinberg equilibrium, which supports the existence of a selective process against some alleles. The average number of variants per individual found in miRNAs was of 28. Despite miRNAs were thought to be a highly conserved genomic element, our study reports a level of variability comparable to what it was observed for coding genes.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000325","title":"Whole genome sequencing of hepatocellular carcinoma tumors and their matched noncancerous liver tissues and the background germline","description":"We performed whole-genome sequencing on multifocal hepatocellular carcinoma tumors and their matched noncancerous liver tissues and the background germline. We found that the noncancerous liver tissues presented varying degrees of genomic alterations that were associated with the background liver diseases. Most of the genomic alterations in the metastatic tumors were inherited from the primary tumor and a small number developed de novo. Few genomic alterations were shared between the multicentric tumors with the exception of the alterations that also existed in the noncancerous liver tissue. Our findings reveal the molecular mechanisms underlying intra-individual tumor evolution on the basis of a global perspective of each lesion. This provides evidence and molecular tools for, in its true sense, personalized molecular cancer medicine.","abstract":"We performed whole-genome sequencing on multifocal hepatocellular carcinoma tumors and their matched noncancerous liver tissues and the background germline. We found that the noncancerous liver tissues presented varying degrees of genomic alterations that were associated with the background liver diseases. Most of the genomic alterations in the metastatic tumors were inherited from the primary tumor and a small number developed de novo. Few genomic alterations were shared between the multicentric tumors with the exception of the alterations that also existed in the noncancerous liver tissue. Our findings reveal the molecular mechanisms underlying intra-individual tumor evolution on the basis of a global perspective of each lesion. This provides evidence and molecular tools for, in its true sense, personalized molecular cancer medicine.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000326","title":"BLUEPRINT ChIP-seq data for cells in the haematopoietic lineages, from adult and cord blood samples.","description":"ChIP-seq data for cells in the haematopoietic lineages, from adult and cord blood samples.","abstract":"ChIP-seq data for cells in the haematopoietic lineages, from adult and cord blood samples.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-08-01T14:27:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000327","title":"BLUEPRINT RNA-seq data for common cells in the haematopoietic lineages, from adult and cord blood samples.","description":"RNA-seq data for common cells in the haematopoietic lineages, from adult and cord blood samples.","abstract":"RNA-seq data for common cells in the haematopoietic lineages, from adult and cord blood samples.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-08-01T14:38:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000328","title":"Sequencing and analysis of a South Asian-Indian personal genome","description":"India with over 1.3 billion people is estimated to carry three times more genetic diversity compared to Europe.  Next-generation sequencing technologies have facilitated the understanding of diversity by enabling whole genome sequencing at greater speed and lower cost.  While multiple genomes from people of European and a few of Asian descent have been sequenced, only recently a single male genome from the Indian subcontinent at sufficient depth and coverage was published.  We have in this study sequenced and analyzed the genome of a South Asian Indian female (SAIF) from the Indian state of Kerala.  We identified over 3.4 million SNPs in this genome including over 89,873 private variations.  Comparison of the SAIF genome with several published personal genomes revealed that this individual shared ~50% of the SNPs with each of these genomes.  Analysis of the SAIF mitochondrial genome showed that it is closely related to the U1a3 haplogroup which has been previously observed in Kerala.  We assessed the SAIF genome for SNPs with health and disease consequences and found that the individual was at a higher risk for multiple sclerosis and a few other diseases.   In assessing SNPs that modulate drug response we found a variation that predicts a favorable response to metformin used for treating diabetes.  SNPs predictive of adverse reaction to warfarin indicated that the SAIF individual is not at risk for bleeding if treated with typical doses of warfarin.  In addition to these, we report the presence of several other SNPs of medical relevance.","abstract":"India with over 1.3 billion people is estimated to carry three times more genetic diversity compared to Europe.  Next-generation sequencing technologies have facilitated the understanding of diversity by enabling whole genome sequencing at greater speed and lower cost.  While multiple genomes from people of European and a few of Asian descent have been sequenced, only recently a single male genome from the Indian subcontinent at sufficient depth and coverage was published.  We have in this study sequenced and analyzed the genome of a South Asian Indian female (SAIF) from the Indian state of Kerala.  We identified over 3.4 million SNPs in this genome including over 89,873 private variations.  Comparison of the SAIF genome with several published personal genomes revealed that this individual shared ~50% of the SNPs with each of these genomes.  Analysis of the SAIF mitochondrial genome showed that it is closely related to the U1a3 haplogroup which has been previously observed in Kerala.  We assessed the SAIF genome for SNPs with health and disease consequences and found that the individual was at a higher risk for multiple sclerosis and a few other diseases.   In assessing SNPs that modulate drug response we found a variation that predicts a favorable response to metformin used for treating diabetes.  SNPs predictive of adverse reaction to warfarin indicated that the SAIF individual is not at risk for bleeding if treated with typical doses of warfarin.  In addition to these, we report the presence of several other SNPs of medical relevance.","study_type":"Whole Genome Sequencing","pubmed_ids":[22938532],"external_links":null,"is_released":true,"released_date":"2012-08-08T11:42:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000329","title":"Identification_of_low_frequency_variants_associated_with_ulcerative_colitis_using_whole_genome_sequencing","description":"2000 ulcerative colitis cases drawn from the UKIBD Genetics  Consortium cohort and whole-genome sequenced at 2X depth. A case  control association study using control samples whole-genome sequenced  by UK10K will be undertaken to identify common, low-frequency and rare  variants associated with ulcerative colitis. Data will be combined  with similar data across 3000 Crohn's disease cases from the same  cohort to identify inflammatory bowel disease (IBD) loci and better  understand the genetic differences and similarities of the two common  forms of IBD.","abstract":"2000 ulcerative colitis cases drawn from the UKIBD Genetics  Consortium cohort and whole-genome sequenced at 2X depth. A case  control association study using control samples whole-genome sequenced  by UK10K will be undertaken to identify common, low-frequency and rare  variants associated with ulcerative colitis. Data will be combined  with similar data across 3000 Crohn's disease cases from the same  cohort to identify inflammatory bowel disease (IBD) loci and better  understand the genetic differences and similarities of the two common  forms of IBD.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-08-09T09:39:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000330","title":"Osteosarcoma_whole_genome_rearrangement_screen","description":"Genomic libraries (500 bps) will be generated from total genomic DNA derived from Osteosarcoma cancer patients and subjected to short paired end sequencing on the llumina platform. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-08-09T10:10:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000331","title":"SOLiD_Lung_study","description":"6 samples from a smoker with non-small cell lung cancer. 3 samples from geographically distinct regions of the same tumor (T1-3), germline derived from blood, non-malignant tobacco exposed parenchymal lung tissue (INF2) and non-malignant tobacco exposed bronchial epithelium(BEC) will be analysed to find mutational processes within this patients tumour.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000332","title":"Helleday_HRAS_Project","description":"This experiment is looking at the mutational signatures generated by engineered HRAS mutations by using whole genome sequence generated on massively parallel next generation sequencers.","abstract":"Looking at the mutational signatures generated by engineered HRAS mutations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-08-09T10:13:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000333","title":"Multiple_Malignancy_Familial_Comparison","description":"Patient (who has had multiple malignancies) has previously been found to harbour a pathogenic p53 variant which is probably mosaic. This finding is based on exome sequencing performed elsewhere. In this study we will resequence the locus in question to ascertain whether the variant is indeed mosaic.","abstract":"Patient (who has had multiple malignancies) has previously been found to harbour a pathogenic p53 variant which is probably mosaic. This finding is based on exome sequencing performed elsewhere. In this study we will resequence the locus in question to ascertain whether the variant is indeed mosaic.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-08-09T10:25:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000334","title":"Genentech Small Cell Lung Cancer (SCLC) Screen","description":"Exome capture, RNA-Seq, whole genome sequencing of set of Small Cell Lung Cancer samples.","abstract":"Exome capture, RNA-Seq, whole genome sequencing of set of Small Cell Lung Cancer samples.","study_type":"Other","pubmed_ids":[22941189],"external_links":null,"is_released":true,"released_date":"2012-08-09T15:46:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000335","title":"A_study_of_the_molecular_pathogenesis_of_Splenic_Marginal_Zone_and_Diffuse_Large_B_Cell_Lymphoma","description":"We will perform exome sequencing on selected cases of splenic marginal zone lymphoma (SMZL) and diffuse large B-cell lymphoma (DLBCL) in order to characterise their genetic makeup and identify biomarkers for prognosis and prediction of treatment response.","abstract":"he genetics and pathogenesis of SMZL are poorly understood.  The lymphoma lacks recurrent chromosome translocation, a common feature in other low grade B-cell lymphomas.   Approximately, 30% of cases have 7q deletion, but the gene targeted by the deletion is unknown.   Although 7q deletion is a characteristic feature of SMZL, clinicopathological investigation and gene expression microarray analyses to date show that the cases with 7q deletion do not constitute a distinct subgroup.   Despite the extensive investigation by array CGH, candidate gene sequencing, gene expression and epigenetic methylation microarray analyses, the molecular pathogenesis of SMZL remains enigmatic.  This is essentially due to a lack of understanding of the key genetic events in this lymphoma entity.   We therefore propose to perform exome sequencing on 15 well characterised SMZL together with the corresponding germline DNA.  The mutations identified will be validated in a large cohort of SMZL by Fluidigm Access Array™ PCR with next generation sequencingDLBCL is a common and aggressive lymphoma and is currently treated with R-CHOP (rituximab-cyclophosphamide, doxorubicin, vincristine and prednisone) or equivalent rituximab-containing chemotherapy regimens.   A major clinical dilemma is that a significant proportion of DLBCL show primary treatment failure (~10%), partial response (~15%)  or relapse after initial responses (20-30%).   Of the cases with lymphoma relapses, the majority show the relapse within the first two years.  Importantly, those resistant to R-CHOP respond poorly to any other currently available treatments, and account for the vast majority of the lymphoma-related death.  Although many biomarkers have been evaluated, only the MYC involved translocation predicts a poor treatment response to R-CHOP and has real value in routine clinical practice.  However, this translocation occurs in only ~10% of DLBCL, clearly not explaining the high proportion of cases resistant to R-CHOP.  We therefore propose to identify the somatic mutations potentially associated with R-CHOP resistance by exome sequencing of 15 MYC translocation-negative DLBCL that showed primary treatment failure, and 10 DLBCL that achieved stable complete remission.  The mutations identified will be validated in a large cohort of DLBCL by Fluidigm Access Array™ PCR with next generation sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-08-10T11:32:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000336","title":"Understanding_population_genetics_and_patterns_of_genome_wide_heterozygosity_in_a_sample_of_the_Croatian_isolated_populations__ESGIDalmatians_","description":"Using high-throughput sequencing technologies and analytical tools, we conduct an exome sequencing study that will help understand the populationgenetics of a Croatian island isolate, in a sample of 200 subjects from the Adriatic island of Vis who wereselected to reflect islanders with at least four known ancestors in grandparental line who are original islanders.","abstract":"Using high-throughput sequencing technologies and analytical tools, we conduct an exome sequencing study that will help understand the populationgenetics of a Croatian island isolate, in a sample of 200 subjects from the Adriatic island of Vis who wereselected to reflect islanders with at least four known ancestors in grandparental line who are original islanders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-08-13T09:37:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000337","title":"Inferring tumor genomes from peripheral blood i.e. CTCs and plasma-DNA using deep sequencing and targeted enrichment","description":"In this study we tested whether complex tumor genomes can be inferred from the peripheral blood (plasma DNA /CTCs) of 32 patients with stage IV colorectal carcinoma (CRC). To establish the percentage of mutated plasma DNA fragments we used 8 patient samples with different plasma DNA size distributions and KRAS mutations in their corresponding primary tumors and employed ultra-deep pyrosequencing with 3 different sequencing reaction sizes (i.e., 119 bp, 168 bp, and 323 bp). Furthermore, we used massive parallel sequencing of a panel of 68 CRC-associated genes to establish the mutation spectrum of cancer driver genes in the primary tumors, metastases, and CTCs of two colorectal cancer patients. To investigate, whether mutations found in only one CTC (“private CTC mutations”) are true mutations occurring with allele frequencies below the resolution limits of current detection methods, or whether they are amplification or sequencing artifacts, we performed ultra-deep sequencing of the primary tumors, metastases, plasma DNAs and normal tissues.","abstract":"In this study we tested whether complex tumor genomes can be inferred from the peripheral blood (plasma DNA /CTCs) of 32 patients with stage IV colorectal carcinoma (CRC). To establish the percentage of mutated plasma DNA fragments we used 8 patient samples with different plasma DNA size distributions and KRAS mutations in their corresponding primary tumors and employed ultra-deep pyrosequencing with 3 different sequencing reaction sizes (i.e., 119 bp, 168 bp, and 323 bp). Furthermore, we used massive parallel sequencing of a panel of 68 CRC-associated genes to establish the mutation spectrum of cancer driver genes in the primary tumors, metastases, and CTCs of two colorectal cancer patients. To investigate, whether mutations found in only one CTC (“private CTC mutations”) are true mutations occurring with allele frequencies below the resolution limits of current detection methods, or whether they are amplification or sequencing artifacts, we performed ultra-deep sequencing of the primary tumors, metastases, plasma DNAs and normal tissues.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-08-14T12:13:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000338","title":"Targeted enrichment of 68 CRC-associated genes","description":"We used massive parallel sequencing of a panel of 68 CRC-associated genes to establish the mutation spectrum of cancer driver genes in the primary tumors, metastases, and CTCs of two colorectal cancer patients","abstract":"We used massive parallel sequencing of a panel of 68 CRC-associated genes to establish the mutation spectrum of cancer driver genes in the primary tumors, metastases, and CTCs of two colorectal cancer patients","study_type":"Other","pubmed_ids":[23471846],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001000339","title":"Deep sequencing of private CTC mutations in corresponding tumors, metastases, plasma DNAs and normal tissues","description":"To investigate, whether mutations found in only one CTC (private CTC mutations) are true mutations occurring with allele frequencies below the resolution limits of current detection methods, or whether they are amplification or sequencing artifacts, we performed ultra-deep sequencing of the primary tumors, metastases, plasma DNAs and normal tissues.","abstract":"To investigate, whether mutations found in only one CTC (private CTC mutations) are true mutations occurring with allele frequencies below the resolution limits of current detection methods, or whether they are amplification or sequencing artifacts, we performed ultra-deep sequencing of the primary tumors, metastases, plasma DNAs and normal tissues.","study_type":"Other","pubmed_ids":[23471846],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001000340","title":"We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (Stage I and II) sporadic Pancreatic Ductal Adenocarcinoma. Detailed analysis of 99 informative tumours identified significant heterogeneity with 2016 non-silent mutations and 1628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations: KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1, and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2); DNA damage repair (ATM), and others (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in-vitro functional data and murine mutagenesis screens provided support for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering of mutations in core signalling pathways in Pancreatic Ductal Adenocarcinoma, and identified new components in each. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling which was also evident in murine Sleeping Beauty-mediated somatic mutagenesis screens, providing further supportive evidence for a potential role for axon guidance genes in pancreatic carcinogenesis.","description":"We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (Stage I and II) sporadic Pancreatic Ductal Adenocarcinoma. Detailed analysis of 99 informative tumours identified significant heterogeneity with 2016 non-silent mutations and 1628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations: KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1, and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2); DNA damage repair (ATM), and others (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in-vitro functional data and murine mutagenesis screens provided support for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering of mutations in core signalling pathways in Pancreatic Ductal Adenocarcinoma, and identified new components in each. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling which was also evident in murine Sleeping Beauty-mediated somatic mutagenesis screens, providing further supportive evidence for a potential role for axon guidance genes in pancreatic carcinogenesis.","abstract":"We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (Stage I and II) sporadic Pancreatic Ductal Adenocarcinoma. Detailed analysis of 99 informative tumours identified significant heterogeneity with 2016 non-silent mutations and 1628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations: KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1, and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2); DNA damage repair (ATM), and others (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in-vitro functional data and murine mutagenesis screens provided support for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering of mutations in core signalling pathways in Pancreatic Ductal Adenocarcinoma, and identified new components in each. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling which was also evident in murine Sleeping Beauty-mediated somatic mutagenesis screens, providing further supportive evidence for a potential role for axon guidance genes in pancreatic carcinogenesis.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000341","title":"Human_host_and_hepatitis_C_virus_genome_diversity_in_a_Ugandan_population","description":"The study will assess human and HCV genome diversity in a rural Ugandan population by sequencing at low coverage (4x) the whole genome of 200 Ugandan individuals previously identified as HCV infected, as well as the corresponding viral genomes.","abstract":"Hepatitis C virus (HCV), a major cause of chronic liver disease, is common in low-income countries, with the highest prevalence in sub-Saharan Africa (SSA). Marked variation in prognosis and response to treatment seems to be largely due to differences in human host and pathogen genome diversity. Preliminary results from the African Genome Variation project show marked genetic variation between 19 ethnolinguistic groups across SSA. In addition to host variation, the hepatitis C virus genome is known to be extremely diverse in this region and the extent of diversity in viral subtypes has not been fully characterised. Understanding host and virus genomic diversity in HCV infection has important implications for understanding the impact of genetic variation on the natural history of disease and treatment response in these populations. Indeed, host and virus genetic variants in hepatitis C are known to be independent predictors of disease progression and treatment response. We plan to assess human and pathogen genome diversity in a rural Ugandan population. Specifically, we will: 1) characterise the diversity of HCV genome sequence in SSA by phylogenetic analysis of whole genome sequences  2) identify novel subtypes of the virus and build a whole genome consensus reference panel for HCV in SSA; 3) examine transmission dynamics of hepatitis C within populations using bayesian coalescent approaches; 4) study the correlation between host and virus genetic diversity and identify viral epitopes under selection pressure from specific host genetic variants; 5) correlate longitudinal changes in sequence diversity with clinically relevant biomarkers, natural viral clearance and hepatic fibrosis in HCV infection; and 6) examine the association between host and virus genetic variation and relevant clinical outcomes, including spontaneous viral clearance and hepatic fibrosis.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000342","title":"Somatic_mutations_in_normal_murine_tissue","description":"Using exome sequencing, the aim of this study is to determine the somatic mutation rate in normal murine tissue from different organs. To this end, we will sequence DNA derived from organoids, ie clonal organ structures derived from single stem cel, from different mouse organs.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina massively parallel sequencing technology, we aim to sequence microRNAs plus the protein coding genome of a number of samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000343","title":"Pancreatic Cancer Sequencing Initiative","description":"Pancreatic Cancer Sequencing Initiative for the International Cancer Genome Consortium at the Ontario Institute for Cancer Research.","abstract":"Pancreatic Cancer Sequencing Initiative for the International Cancer Genome Consortium at the Ontario Institute for Cancer Research.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-08-22T12:48:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000344","title":"Exome_sequencing_of_thyroid_disease_in_Val_Borbera","description":"The Val Borbera  is a region characterized by low iodine and high prevalence of thyroid disorders, the commonest endocrine disorders in the general population.  About 30% of the participants of the Val Borbera Project were affected by such disorders and were characterized by several parameters, TSH level, anti TPO antibodies, echography, family origin. Individuals with extreme phenotypes were identified and could be clustered based on family origin and genotype.  We propose to exome sequence  6 of them, affected with true goiter,  at high dept (40-60x) to obtain information on exonic  rare variants.  Due to the family structure and to the availability of whole genome sequence information on 110 individuals from the isolated population we expect to be able to identify putative causative variants for thyroid disorders that may be studied in the remaining affected individuals.","abstract":"The Val Borbera  is a region characterized by low iodine and high prevalence of thyroid disorders, the commonest endocrine disorders in the general population.  About 30% of the participants of the Val Borbera Project were affected by such disorders and were characterized by several parameters, TSH level, anti TPO antibodies, echography, family origin. Individuals with extreme phenotypes were identified and could be clustered based on family origin and genotype.  We propose to exome sequence  6 of them, affected with true goiter,  at high dept (40-60x) to obtain information on exonic  rare variants.  Due to the family structure and to the availability of whole genome sequence information on 110 individuals from the isolated population we expect to be able to identify putative causative variants for thyroid disorders that may be studied in the remaining affected individuals.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-08-23T12:48:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000345","title":"UK10K NEURO GURLING","description":"This sample set consists of DNA from multiply affected  schizophrenia families. The families have been diagnosed using the SADS-L clinical instrument  which gives diagnoses at the probable level of the research diagnostic criteria (RDC). In  addition all diagnoses are available using DSMIIIR criteria. These criteria are widely accepted  as being valid and reliable for the diagnosis of schizophrenia. All families have been collected to  ensure that they are uni-lineal for transmission of schizophrenia, i.e. they have only one affected  parent with schizophrenia, or a relative of only one transmitting or obligate carrier parent with  schizophrenia. Families with bi-lineal transmission of schizophrenia (i.e. with both parents being  affected) were not sampled for this study. All families have multiple cases of schizophrenia and  related disorders. The families have been selected to ensure there  are no cases of bipolar  disorder within them and that they do not contain bipolar disorder in any relatives on either side  of the family.","abstract":"This sample set consists of DNA from multiply affected  schizophrenia families. The families have been diagnosed using the SADS-L clinical instrument  which gives diagnoses at the probable level of the research diagnostic criteria (RDC). In  addition all diagnoses are available using DSMIIIR criteria. These criteria are widely accepted  as being valid and reliable for the diagnosis of schizophrenia. All families have been collected to  ensure that they are uni-lineal for transmission of schizophrenia, i.e. they have only one affected  parent with schizophrenia, or a relative of only one transmitting or obligate carrier parent with  schizophrenia. Families with bi-lineal transmission of schizophrenia (i.e. with both parents being  affected) were not sampled for this study. All families have multiple cases of schizophrenia and  related disorders. The families have been selected to ensure there  are no cases of bipolar  disorder within them and that they do not contain bipolar disorder in any relatives on either side  of the family.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000346","title":"Genetic landscape of pediatric Retinoblastoma","description":"Retinoblastoma is a pediatric cancer of the developing retina. All retinoblastomas are believed to initiate with biallelic inactivation of the RB1 gene. To identify subsequent genetic lesions in retinoblastoma, we performed whole genome sequencing of tumor and normal DNA of 4 children with retinoblastoma and one matched orthotopic xenograft. Both alleles of RB1 were inactivated in the tumor samples. 3 of the patients had sporadic retinoblastoma and one patient had inherited retinoblastoma. Overall, there were few single nucleotide changes in coding regions of the genome and some of the tumors had few chromosomal lesions. There were very few new genetic lesions in the xenograft compared to the primary tumor. These data suggest that the genome in retinoblastoma is more stable than previously believed and there are relatively few recurrent genetic lesions in known cancer pathways other than the RB1 pathway.","abstract":"Retinoblastoma is a pediatric cancer of the developing retina. All retinoblastomas are believed to initiate with biallelic inactivation of the RB1 gene. To identify subsequent genetic lesions in retinoblastoma, we performed whole genome sequencing of tumor and normal DNA of 4 children with retinoblastoma and one matched orthotopic xenograft. Both alleles of RB1 were inactivated in the tumor samples. 3 of the patients had sporadic retinoblastoma and one patient had inherited retinoblastoma. Overall, there were few single nucleotide changes in coding regions of the genome and some of the tumors had few chromosomal lesions. There were very few new genetic lesions in the xenograft compared to the primary tumor. These data suggest that the genome in retinoblastoma is more stable than previously believed and there are relatively few recurrent genetic lesions in known cancer pathways other than the RB1 pathway.","study_type":"Whole Genome Sequencing","pubmed_ids":[22237022],"external_links":null,"is_released":true,"released_date":"2012-08-24T17:09:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000347","title":"Genetic landscape of pediatric Medulloblastoma","description":"Medulloblastoma is a heterogenous disease made up of at least four distinct subtypes of disease which appear to exploit and disrupt naturally occurring developmental pathways of cellular growth and hindbrain development. To better understand the driver mutations of this disease, we performed whole genome sequencing of 37 medulloblastomas and the corresponding normal DNA of the 37 affected children treated at St. Jude Children's Research Hospital. We have found several novel mutations which appear subtype specific. These mutations were checked for frequency in a separate tumor cohort of 56 children with medulloblastoma, also treated on the St. Jude Medulloblastoma 2003 trial, and were tested in several animal models of medulloblastoma for proof of oncogenic potential.","abstract":"Medulloblastoma is a heterogenous disease made up of at least four distinct subtypes of disease which appear to exploit and disrupt naturally occurring developmental pathways of cellular growth and hindbrain development. To better understand the driver mutations of this disease, we performed whole genome sequencing of 37 medulloblastomas and the corresponding normal DNA of the 37 affected children treated at St. Jude Children's Research Hospital. We have found several novel mutations which appear subtype specific. These mutations were checked for frequency in a separate tumor cohort of 56 children with medulloblastoma, also treated on the St. Jude Medulloblastoma 2003 trial, and were tested in several animal models of medulloblastoma for proof of oncogenic potential.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-08-24T17:12:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000348","title":"Genetic landscape of Early T-cell precursor acute lymphoblastic leukaemia","description":"Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.","abstract":"Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.","study_type":"Whole Genome Sequencing","pubmed_ids":[21666668],"external_links":null,"is_released":true,"released_date":"2012-08-24T17:15:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000349","title":"The Genomic Landscape of Core-Binding Factor Acute Myeloid Leukemias","description":"Pediatric de novo acute myeloid leukemia (AML) is a heterogeneous disease that can be divided into clinically distinct subtypes based on the presence of specific chromosomal abnormalities or gene alterations. One of the best characterized subtypes of AML involves leukemias with alterations of the core-binding factor (CBF)-complex, which comprises the FAB subtypes M2 and M4Eo and associates with a favorable outcome. Patients with the AML M2 subtype harbor a translocation between chromosomes 8 and 21 [t(8;21)] that yields the chimeric fusion gene RUNX1(AML1)-RUNX1T1(ETO), while patients with AML M4Eo express the chimeric fusion gene CBFβ-SMMHC(MYH11) as a result of an inversion/translocation event of chromosome 16 [inv(16)/t(16;16)]. In an effort to define the total complement of genetic changes in CBF-leukemia, we performed paired-end whole genome sequencing (WGS) on diagnostic leukemia blasts and matched germ line samples from 17 pediatric CBF-leukemia patients using the Illumina platform. Somatic alterations, including single nucleotide variations (SNVs) and structural variations (SVs), including insertions, deletions, inversions, and inter- and intra-chromosomal rearrangements, were detected using complementary analysis pipelines (Bambino, CREST and CONSERTING). Recurrent screening of identified mutations will be performed in a cohort of approximately 94 cases of CBF-leukemias.","abstract":"Pediatric de novo acute myeloid leukemia (AML) is a heterogeneous disease that can be divided into clinically distinct subtypes based on the presence of specific chromosomal abnormalities or gene alterations. One of the best characterized subtypes of AML involves leukemias with alterations of the core-binding factor (CBF)-complex, which comprises the FAB subtypes M2 and M4Eo and associates with a favorable outcome. Patients with the AML M2 subtype harbor a translocation between chromosomes 8 and 21 [t(8;21)] that yields the chimeric fusion gene RUNX1(AML1)-RUNX1T1(ETO), while patients with AML M4Eo express the chimeric fusion gene CBFβ-SMMHC(MYH11) as a result of an inversion/translocation event of chromosome 16 [inv(16)/t(16;16)]. In an effort to define the total complement of genetic changes in CBF-leukemia, we performed paired-end whole genome sequencing (WGS) on diagnostic leukemia blasts and matched germ line samples from 17 pediatric CBF-leukemia patients using the Illumina platform. Somatic alterations, including single nucleotide variations (SNVs) and structural variations (SVs), including insertions, deletions, inversions, and inter- and intra-chromosomal rearrangements, were detected using complementary analysis pipelines (Bambino, CREST and CONSERTING). Recurrent screening of identified mutations will be performed in a cohort of approximately 94 cases of CBF-leukemias.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-08-24T17:18:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000350","title":"Exome_sequencing_in_two_richly_phenotyped_European_population_isolates___identifying_rare_and_population_specific_variants__ESGI_ISOLATEXOME_","description":"The aim of this project is to identify exome variants in two population isolates using whole exome sequencing of 200 subjects from the ORCADES and NSPHS cohorts.","abstract":"The aim of this project is to identify exome variants in two population isolates using whole exome sequencing of 200 subjects from the ORCADES and NSPHS cohorts.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000351","title":"BLUEPRINT DNase accessibility (NCMLS)","description":"DNase accessibility study","abstract":"DNase accessibility study","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-08-28T13:40:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000352","title":"Epilepsy_related_sudden_death","description":"These samples include exome sequences of samples from patients who suffered Sudden Unexplained Death in Epilepsy","abstract":"These samples include exome sequences of samples from patients who suffered Sudden Unexplained Death in Epilepsy","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-08-29T09:23:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000353","title":"The_genomic_architecture_of_mesothelioma_","description":"The genome-wide landscape of somatically acquired mutations in mesothelioma has not been deeply characterised to date, but advances in DNA sequencing technology now allow this to be addressed comprehensively. Harnessing massively parallel DNA sequencing platforms, we will identify somatically acquired point mutations in all coding regions of the genome from patients with mesothelioma. In addition, using paired-end sequencing, we will map copy number changes and genomic rearrangements from the same patients.","abstract":"Cancer is driven by the acquisition of mutations in genes co-ordinating key biological pathways. Discovering recurrently mutated genes in a given tumour type provides direct access to disease biology and potentially identifies novel therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-08-31T10:55:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000354","title":"Primary_Lung_Cancer_whole_genome_study","description":"Genomic libraries (500 bps) will be generated from total genomic DNA derived from lung cancer patients and subjected to short paired end sequencing on the llumina platform. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemias, lymphomas and soft tissue tumors. However, conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution. We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-08-31T16:25:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000355","title":"Pancreatic Cancer Genomes Reveal Aberrations in Axon Guidance Pathway Genes","description":null,"abstract":null,"study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000356","title":"Exome_sequencing_of_Bilateral_Anophthalmia_cases__Pilot_Study_","description":"This pilot study aims to generate pilot data to inform future study designs by resequencing the whole exomes of 10 unrelated individuals diagnosed with Bilateral Anophthalmia.","abstract":"This pilot study aims to generate pilot data to inform future study designs by resequencing the whole exomes of 10 unrelated individuals diagnosed with Bilateral Anophthalmia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-09-04T16:28:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000357","title":"Exome sequencing of a paraganglioma and matched blood sample identifies biallelic inactivation of the FH gene, associated with a hypermethylator phenotype.","description":"We analyzed genome-scale DNA methylation changes in a series of 145 pheochromocytomas (PCC) and paragangliomas (PGL). Unsupervised clustering identified a homogeneous cluster of tumors displaying concerted hypermethylation at a large number of CpG sites. All but one hypermethylated tumors harbored mutations affecting succinate dehydrogenase (SDH). Exome sequencing of the only sample displaying a hypermethylator phenotype while harboring no SDH mutation revealed two mutations (one somatic and one germinal) in the FH gene. These data demonstrate for the first time the implication of FH in PCC/PGL, and emphasize the interplay between the citric acid cycle and epigenomic alterations in cancer.","abstract":"We analyzed genome-scale DNA methylation changes in a series of 145 pheochromocytomas (PCC) and paragangliomas (PGL). Unsupervised clustering identified a homogeneous cluster of tumors displaying concerted hypermethylation at a large number of CpG sites. All but one hypermethylated tumors harbored mutations affecting succinate dehydrogenase (SDH). Exome sequencing of the only sample displaying a hypermethylator phenotype while harboring no SDH mutation revealed two mutations (one somatic and one germinal) in the FH gene. These data demonstrate for the first time the implication of FH in PCC/PGL, and emphasize the interplay between the citric acid cycle and epigenomic alterations in cancer.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000358","title":"Sequencing_the_exome_of_12_early_sporadic_human_colorectal_cancers__CRC_","description":"In the project we sequenced the exomes of tumour from patients with germline mutations in APC i.e. FAP patients. The aim of the study was to determine the load of mutations acquired during the early staged of tumour development in these patients with the aim of determining the rate mutation acquisition.","abstract":"In the project we sequenced the exomes of tumour from patients with germline mutations in APC i.e. FAP patients. The aim of the study was to determine the load of mutations acquired during the early staged of tumour development in these patients with the aim of determining the rate mutation acquisition.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-09-05T11:31:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000359","title":"Mutation_analysis_in_human_iPS_cells_","description":"PCR products were obtained from each target loci using genomic DNA from human iPS cells. Subsequently, PCR products are pooled and subjected to Illumina library preparation.  The library will be sequenced by MiSeq. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Human iPS cells could offer the prospect of autologous cell-replecement therapy to treat patients with genetic diseases. We have previously shown that disease-causing mutations could be fixed in iPS cells without additional damages to the iPS cell genome. To more deeply analyze the modified iPS cell genome, we seqeunced whole genome of those iPS cell lines and identified SNVs. This MiSeq study is to validate these SNVs.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-09-05T11:58:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000360","title":"Balanced_Brain_Tumour_Whole_Genome_Sequencing","description":"We propose to definitively characterise the somatic genetics of a number of pediatric malignant tumours including ependymoma, high grade glioma and central nervous system primitive neurectodermal tumours through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-09-07T11:10:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000362","title":"Ewings_Sarcoma_Rearrangement_Screen","description":"Cancer is driven by mutations in the genome. We will uncover the mutations that give rise to Ewing’s sarcoma, a bone tumour that largely affects children. We will use second generation Illumina massively parallel sequencing, and bespoke software, to characterise the genomes and transcriptomes of Ewings’ sarcoma tumours.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-09-07T11:39:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000363","title":"APCDR AGV Project: WGS of an Ugandan population","description":"The African Genome Variation Project (AGVP) provides a resource to help design, implement and interpret genomic studies in sub-Saharan Africa (SSA) and worldwide. The AGVP represents dense genotypes from 1,481 and whole genome sequences (WGS) from 320 individuals across SSA. \nAs part of the AGVP we sequenced the genome of 100 unrelated Baganda from rural Uganda to about 4x depth.","abstract":"The African Genome Variation Project (AGVP) provides a resource to help design, implement and interpret genomic studies in sub-Saharan Africa (SSA) and worldwide. The AGVP represents dense genotypes from 1,481 and whole genome sequences (WGS) from 320 individuals across SSA. \nAs part of the AGVP we sequenced the genome of 100 unrelated Baganda from rural Uganda to about 4x depth.","study_type":"Other","pubmed_ids":[25470054],"external_links":null,"is_released":true,"released_date":"2012-09-13T17:18:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000364","title":"Chromatin_structure_in_human_IPS_RNA","description":"e will carry out six assays in 10 IPS lines derived from skin different tissues collected from five separate individuals. Each set of assays will be carried out in two colonies from each individual to assess variation between different colonies. We will also perform the six assays twice within a culture derived from the same colony to assess the technical variability of our assays. Each colony will be screened by array CGH during passages 3-5 to remove colonies with very large deletions of rearrangements prior to culture. The assays we will perform are: FAIRE (formaldehyde-assisted isolation of regulatory elements)-seq (chromatin openness), ChIP (chromatin immunoprecipitation)-seq for H3K4me3 (active promoters), ChIP-seq for H3K27ac (active enhancers) ChIP-seq for H3K27me3 (silent &amp; bivalent promoters, enhancers) and RNA-seq (transcription). By mapping reads to different alleles, we will be able to identify allele-specific effects on epigenetic marks and chromatin accessibility.Total RNA is extracted with TRIzol reagent before performing NGS.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Epigenetic and gene expression differences are known to occur between human induced pluripotent stem cell lines. Identifying the sources of this variation, and their relative importance in determining the transcriptional and epigenetic landscape of hIPSCs is important for understanding the biology of cellular reprogramming, and for informing efforts to improve the quality and differentiation potential of IPS lines. Two likely sources of variation are experimental or cellular variability introduced by reprogramming and genetic variation between different progenitor cells from which the hIPSCs were derived. This project will investigate the relative importance of these two factors in introducing epigenetic and gene expression variation between human IPS lines.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000365","title":"Chromatin_structure_in_human_IPS_FAIRE","description":"e will carry out six assays in 10 IPS lines derived from skin different tissues collected from five separate individuals. Each set of assays will be carried out in two colonies from each individual to assess variation between different colonies. We will also perform the six assays twice within a culture derived from the same colony to assess the technical variability of our assays. Each colony will be screened by array CGH during passages 3-5 to remove colonies with very large deletions of rearrangements prior to culture. The assays we will perform are: FAIRE (formaldehyde-assisted isolation of regulatory elements)-seq (chromatin openness), ChIP (chromatin immunoprecipitation)-seq for H3K4me3 (active promoters), ChIP-seq for H3K27ac (active enhancers) ChIP-seq for H3K27me3 (silent &amp; bivalent promoters, enhancers) and RNA-seq (transcription). By mapping reads to different alleles, we will be able to identify allele-specific effects on epigenetic marks and chromatin accessibility.FAIRE material is generated from cells or tissue that are cross-linked briefly with formaldehyde, lysed and sonicated. Sheared chromatin is subject to phenol/chloroform extraction. DNA not cross-linked to protein (typically those regions from open chromatin) will segregate in the aqueous phase, whilst DNA cross-linked to protein will segregate between the organinc and aqueous phases. FAIRE DNA is recovered from the aqueous phase and followed by next-generation sequencing (NGS).This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Epigenetic and gene expression differences are known to occur between human induced pluripotent stem cell lines. Identifying the sources of this variation, and their relative importance in determining the transcriptional and epigenetic landscape of hIPSCs is important for understanding the biology of cellular reprogramming, and for informing efforts to improve the quality and differentiation potential of IPS lines. Two likely sources of variation are experimental or cellular variability introduced by reprogramming and genetic variation between different progenitor cells from which the hIPSCs were derived. This project will investigate the relative importance of these two factors in introducing epigenetic and gene expression variation between human IPS lines.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000366","title":"Chromatin_structure_in_human_IPS_ChIP","description":"e will carry out six assays in 10 IPS lines derived from skin different tissues collected from five separate individuals. Each set of assays will be carried out in two colonies from each individual to assess variation between different colonies. We will also perform the six assays twice within a culture derived from the same colony to assess the technical variability of our assays. Each colony will be screened by array CGH during passages 3-5 to remove colonies with very large deletions of rearrangements prior to culture. The assays we will perform are: FAIRE (formaldehyde-assisted isolation of regulatory elements)-seq (chromatin openness), ChIP (chromatin immunoprecipitation)-seq for H3K4me3 (active promoters), ChIP-seq for H3K27ac (active enhancers) ChIP-seq for H3K27me3 (silent &amp; bivalent promoters, enhancers) and RNA-seq (transcription). By mapping reads to different alleles, we will be able to identify allele-specific effects on epigenetic marks and chromatin accessibility.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ChIP material is generated from cells or tissue that are cross-linked briefly with formaldehyde, lysed and sonicated. Protein–DNAcomplexesare captured using antibodies specific to the histone of interest. Following cross-link reversal, the ChIP DNA is recovered and then subject to NGS.","abstract":"Epigenetic and gene expression differences are known to occur between human induced pluripotent stem cell lines. Identifying the sources of this variation, and their relative importance in determining the transcriptional and epigenetic landscape of hIPSCs is important for understanding the biology of cellular reprogramming, and for informing efforts to improve the quality and differentiation potential of IPS lines. Two likely sources of variation are experimental or cellular variability introduced by reprogramming and genetic variation between different progenitor cells from which the hIPSCs were derived. This project will investigate the relative importance of these two factors in introducing epigenetic and gene expression variation between human IPS lines.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000367","title":"Assessment_of_genetic_and_epigenetic_variation_in_human_IPS_cells_RNA","description":"In order to progress human induced pluripotent stem cells (hiPSCs) towards the clinic, several outstanding questions must be addressed. It is possible to reprogram different somatic cell types into hiPSCs  and from studies in the mouse, it appears that an epigenetic memory of the starting cell type is carried over to hiPSCs. However a comprehensive comparative study of the characteristics of these hiPSCs has been missing from the literature. Importantly studies which aimed to address these aspects of hiPSCs have used cells from different patients. In order to avoid this important confounding variable and to keep the genetic background constant, tissue samples were procured from the patients and reprogrammed to iPS cells. The transcriptomes of these iPS cells will be compared.\nProtocol: primary cultures of cells were reprogrammed to iPS cells. RNA was extracted using a standard column extraction kit.","abstract":"In order to progress human induced pluripotent stem cells (hiPSCs) towards the clinic, several outstanding questions must be addressed. It is possible to reprogram different somatic cell types into hiPSCs  and from studies in the mouse, it appears that an epigenetic memory of the starting cell type is carried over to hiPSCs. However a comprehensive comparative study of the characteristics of these hiPSCs has been missing from the literature. Importantly studies which aimed to address these aspects of hiPSCs have used cells from different patients. In order to avoid this important confounding variable and to keep the genetic background constant, tissue samples were procured from the patients and reprogrammed to iPS cells. The transcriptomes of these iPS cells will be compared.\nProtocol: primary cultures of cells were reprogrammed to iPS cells. RNA was extracted using a standard column extraction kit.","study_type":"Other","pubmed_ids":[24901476],"external_links":null,"is_released":true,"released_date":"2012-10-02T15:03:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000368","title":"Exome_sequencing_of_Congenital_Heart_Disease_families_from_the_Competence_Network_Berlin","description":"This project aims to study exomes from families and trios withcongenital heart disease (CHD). The samples have been collected underthe Competence Network - Congenital Heart Defects in Berlin, Germany.The phenotypes are mainly left ventricular outflow obstruction (aorticstenosis, bicuspd aortic valve disease coarctation and hypoplasticleft heart), but will also include samples with hypoplastic rightheart and atrioventricular septal defects. We will perform whole exomesequencing using Agilent sequence capture and Illumina HiSeqsequencing.","abstract":"This project aims to study exomes from families and trios withcongenital heart disease (CHD). The samples have been collected underthe Competence Network - Congenital Heart Defects in Berlin, Germany.The phenotypes are mainly left ventricular outflow obstruction (aorticstenosis, bicuspd aortic valve disease coarctation and hypoplasticleft heart), but will also include samples with hypoplastic rightheart and atrioventricular septal defects. We will perform whole exomesequencing using Agilent sequence capture and Illumina HiSeqsequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-10-05T11:56:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000369","title":"Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma","description":"Neuroblastomas are tumors of peripheral sympathetic neurons and are the most common solid tumor in children.   To determine the genetic basis for neuroblastoma we performed whole-genome sequencing (6 cases), exome sequencing (16 cases), genome-wide rearrangement analyses (32 cases), and targeted analyses of specific genomic loci (40 cases) using massively parallel sequencing.    On average each tumor had 19 somatic alterations in coding genes (range, 3-70).  Among genes not previously known to be involved in neuroblastoma, chromosomal deletions and sequence alterations of chromatin remodeling genes, ARID1A and ARID1B, were identified in 8 of 71 tumors (11%) and were associated with early treatment failure and decreased survival.  Using tumor-specific structural alterations, we developed an approach to identify rearranged DNA fragments in sera, providing personalized biomarkers for minimal residual disease detection and monitoring.  These results highlight dysregulation of chromatin remodeling in pediatric tumorigenesis and provide new approaches for the management of neuroblastoma patients.Data Provider: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (SKCCC)","abstract":"Neuroblastomas are tumors of peripheral sympathetic neurons and are the most common solid tumor in children.   To determine the genetic basis for neuroblastoma we performed whole-genome sequencing (6 cases), exome sequencing (16 cases), genome-wide rearrangement analyses (32 cases), and targeted analyses of specific genomic loci (40 cases) using massively parallel sequencing.    On average each tumor had 19 somatic alterations in coding genes (range, 3-70).  Among genes not previously known to be involved in neuroblastoma, chromosomal deletions and sequence alterations of chromatin remodeling genes, ARID1A and ARID1B, were identified in 8 of 71 tumors (11%) and were associated with early treatment failure and decreased survival.  Using tumor-specific structural alterations, we developed an approach to identify rearranged DNA fragments in sera, providing personalized biomarkers for minimal residual disease detection and monitoring.  These results highlight dysregulation of chromatin remodeling in pediatric tumorigenesis and provide new approaches for the management of neuroblastoma patients.Data Provider: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (SKCCC)","study_type":"Other","pubmed_ids":[23202128],"external_links":null,"is_released":true,"released_date":"2012-10-08T17:25:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000370","title":"Cancer genome scanning in plasma: detection of tumor-associated copy number aberrations, single nucleotide variants and tumoral heterogeneity by massively parallel sequencing","description":"Tumor-derived DNA can be found in the plasma of cancer patients. We explored the use of shotgun massively parallel sequencing of plasma DNA obtained from cancer patients to scan a cancer genome noninvasively. We achieved the profiling of copy number aberrations and point mutations, in a genomewide manner using this approach. By measuring the genomewide aggregated allelic loss and point mutations, we determined the fractional tumor-derived DNA concentrations in plasma and correlated these values with tumor size and surgical treatment. We have also demonstrated the application of this approach to monitoring a complex oncologic scenario, in a patient with two synchronous cancers. In particular, through the use of multi-regional sequencing of tumoral tissues and shotgun sequencing of plasma DNA, we have shown that plasma DNA sequencing is a valuable approach for studying tumoral heterogeneity. Shotgun plasma DNA sequencing is thus a powerful tool for cancer monitoring and research.","abstract":"Tumor-derived DNA can be found in the plasma of cancer patients. We explored the use of shotgun massively parallel sequencing of plasma DNA obtained from cancer patients to scan a cancer genome noninvasively. We achieved the profiling of copy number aberrations and point mutations, in a genomewide manner using this approach. By measuring the genomewide aggregated allelic loss and point mutations, we determined the fractional tumor-derived DNA concentrations in plasma and correlated these values with tumor size and surgical treatment. We have also demonstrated the application of this approach to monitoring a complex oncologic scenario, in a patient with two synchronous cancers. In particular, through the use of multi-regional sequencing of tumoral tissues and shotgun sequencing of plasma DNA, we have shown that plasma DNA sequencing is a valuable approach for studying tumoral heterogeneity. Shotgun plasma DNA sequencing is thus a powerful tool for cancer monitoring and research.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-10-08T23:49:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000371","title":"Whole-exome study to identify the causative germline mutations of congenital macrothrombocytopenia","description":"To identify the causative germline mutations of congenital macrothrombocytopenia, whole-exome study of 6 families (21 individuals) with autosomal dominant mode of transmission.","abstract":"To identify the causative germline mutations of congenital macrothrombocytopenia, whole-exome study of 6 families (21 individuals) with autosomal dominant mode of transmission.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-10-09T13:53:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000372","title":"Poly(A) RNA sequencing of hepatocellular carcinoma tumors and their matched noncancerous liver tissues","description":"We performed poly(A) RNA sequencing on multiple hepatocellular carcinoma tumors and their matched noncancerous liver tissues.","abstract":"We performed poly(A) RNA sequencing on multiple hepatocellular carcinoma tumors and their matched noncancerous liver tissues.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000373","title":"Deep_sequencing_analysis_of_human_iPSC_specific_SNVs_in_donor_cell_population","description":"CR products were obtained from each target loci using genomic DNA from human iPS cells. Subsequently, PCR products are pooled and subjected to Illumina library preparation.  The library will be sequenced either by HiSeq or MiSeq. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Human induced pluripotent stem (iPS) cells could offer the prospect of autologous cell-replacement therapy to treat patients with genetic diseases. It is now known that human iPS cells carry tens of point mutations compared to the donor genome and often carry copy number changes. For safe use of human iPS cells in clinic, understanding the integrity of the iPS cell genome is important. We have analysed how these point mutations were introduced into the iPS cells genome by whole genome sequencing of iPS cells derived from monoclonal primary somatic cells. We found that 500-1000 SNVs were introduced during primary cell culture and reprogramming. We would like to perform deep sequencing of these SNVs in parental population to analyse the rate of culture-induced mutations.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-10-11T10:00:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000374","title":"Deep RNA sequencing in CLL","description":"Chronic lymphocytic leukemia (CLL) is a B-cell neoplasm with a heterogeneous clinical and biological behavior.  We have performed deep RNA sequencing in different subpopulations of B-lymphocytes from healthy individuals and CLL cells from a cohort of 98 patients, and characterized the CLL transcriptional landscape with unprecedented resolution. The transcriptomic architecture of CLL uncovered here refines the biological characterization of the disease and opens new perspectives for the clinical management of patients.","abstract":"Chronic lymphocytic leukemia (CLL) is a B-cell neoplasm with a heterogeneous clinical and biological behavior.  We have performed deep RNA sequencing in different subpopulations of B-lymphocytes from healthy individuals and CLL cells from a cohort of 98 patients, and characterized the CLL transcriptional landscape with unprecedented resolution. The transcriptomic architecture of CLL uncovered here refines the biological characterization of the disease and opens new perspectives for the clinical management of patients.","study_type":"Other","pubmed_ids":[24265505],"external_links":null,"is_released":true,"released_date":"2012-10-11T13:56:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000375","title":"Exome sequencing of paired tumor/normal DNA samples from the eight intrahepatic cholangiocarcinoma patients","description":"Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy after hepatocellular carcinoma, with increasing incidence worldwide. To gain new insight into the genetic basis of ICC, we performed whole-exome sequencing of paired tumor/normal DNA samples from the 8 ICC patients. The patients underwent surgical resection at the Liver Cancer Institute, Zhongshan Hospital of Fudan University. The study was approved by the Zhongshan Hospital Ethics Committee, and informed consent was obtained from each patients under Institutional Review Board protocols. Tumor tissue was analyzed by frozen section to assess neoplastic cellularity (above 80%). Normal tissue was also analyzed by frozen section to confirm the presence of only non-neoplastic tissue. The clinical information associated with these ICC tumors included sex, age, tumor size, differentiation and TNM stage. DNA libraries were prepared according to the Illumina library generation protocol version 2.3. Each sample was tagged with a custom-designed unique 4-base-long index within the Illumina adaptor, pooled, captured by TruSeq Exome Enrichment Kit and sequenced using Illumina Hiseq2000 system.","abstract":"Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy after hepatocellular carcinoma, with increasing incidence worldwide. To gain new insight into the genetic basis of ICC, we performed whole-exome sequencing of paired tumor/normal DNA samples from the 8 ICC patients. The patients underwent surgical resection at the Liver Cancer Institute, Zhongshan Hospital of Fudan University. The study was approved by the Zhongshan Hospital Ethics Committee, and informed consent was obtained from each patients under Institutional Review Board protocols. Tumor tissue was analyzed by frozen section to assess neoplastic cellularity (above 80%). Normal tissue was also analyzed by frozen section to confirm the presence of only non-neoplastic tissue. The clinical information associated with these ICC tumors included sex, age, tumor size, differentiation and TNM stage. DNA libraries were prepared according to the Illumina library generation protocol version 2.3. Each sample was tagged with a custom-designed unique 4-base-long index within the Illumina adaptor, pooled, captured by TruSeq Exome Enrichment Kit and sequenced using Illumina Hiseq2000 system.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000376","title":"Genomic pathology of SLE-associated copy number variation at the FCGR2C/3B/2B locus","description":"Reduced FCGR3B copy number is associated with increased risk of systemic lupus erythematosus (SLE). The five FCGR2/3 genes are arranged across two highly paralogous genomic segments on chromosome 1q23. Previous studies have suggested mechanisms for structural rearrangements at the FCGR2/3 locus and have proposed mechanisms whereby altered FCGR3B copy number predisposes to autoimmunity, but the high degree of sequence similarity between paralogous genes and segments has prevented precise definition of the molecular events and their functional consequences. To pursue the genomic pathology associated with FCGR3B copy number variation (CNV), we integrated sequencing data from fosmid and BAC clones and sequence-captured DNA from FCGR3B-deleted genomes to establish a detailed map of allelic and paralogous sequence variation across the FCGR2/3 locus. This analysis identified two highly paralogous 24.5kb blocks within the FCGR2C/FCGR3B/FCGR2B locus that are devoid of non-polymorphic paralogous sequence variations (PSVs) and that define the limits of the genomic regions in which non-allelic homologous recombination leads to FCGR2C/3B CNV. Further, the data showed evidence of swapping of haplotype blocks between these highly paralogous blocks that most likely has arisen from sequential ancestral recombination events across the region. Functionally, we found by flow cytometry, western blotting and cDNA sequencing that individuals with FCGR3B-deleted alleles show ectopic expression of Fc-gamma RIIb on natural killer cells. We conclude that FCGR3B deletion juxtaposes the 5´-regulatory sequences of FCGR2C with the coding sequence of FCGR2B, creating a chimeric gene from which Fc-gamma RIIb is expressed ectopically on NK cells and provides a new explanation for SLE risk associated with reduced FCGR3B gene copy number.","abstract":"Reduced FCGR3B copy number is associated with increased risk of systemic lupus erythematosus (SLE). The five FCGR2/3 genes are arranged across two highly paralogous genomic segments on chromosome 1q23. Previous studies have suggested mechanisms for structural rearrangements at the FCGR2/3 locus and have proposed mechanisms whereby altered FCGR3B copy number predisposes to autoimmunity, but the high degree of sequence similarity between paralogous genes and segments has prevented precise definition of the molecular events and their functional consequences. To pursue the genomic pathology associated with FCGR3B copy number variation (CNV), we integrated sequencing data from fosmid and BAC clones and sequence-captured DNA from FCGR3B-deleted genomes to establish a detailed map of allelic and paralogous sequence variation across the FCGR2/3 locus. This analysis identified two highly paralogous 24.5kb blocks within the FCGR2C/FCGR3B/FCGR2B locus that are devoid of non-polymorphic paralogous sequence variations (PSVs) and that define the limits of the genomic regions in which non-allelic homologous recombination leads to FCGR2C/3B CNV. Further, the data showed evidence of swapping of haplotype blocks between these highly paralogous blocks that most likely has arisen from sequential ancestral recombination events across the region. Functionally, we found by flow cytometry, western blotting and cDNA sequencing that individuals with FCGR3B-deleted alleles show ectopic expression of Fc-gamma RIIb on natural killer cells. We conclude that FCGR3B deletion juxtaposes the 5´-regulatory sequences of FCGR2C with the coding sequence of FCGR2B, creating a chimeric gene from which Fc-gamma RIIb is expressed ectopically on NK cells and provides a new explanation for SLE risk associated with reduced FCGR3B gene copy number.","study_type":"Other","pubmed_ids":[23261299],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000377","title":"Triple_Negative_Breast_Cancer_RNA_Sequencing","description":"We propose to definitively characterise the somatic genetics of triple negative breast cancer through generation of comprehensive catalogues of somatic mutations in breast cancer cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes and transcriptomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-10-18T17:42:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000378","title":"Triple_Negative_Breast_Cancer_RNA_Sequencing_Validation_Study","description":"Using targeted re-sequencing methods, this study aims to validate the findings found in whole transcriptome sequencing of triple negative breast cancer.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes and transcriptomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000379","title":"Genetic landscape of non-Down syndrome acute megkaryoblastic leukemia","description":"To define the mutation spectrum in non-Down syndrome acute megkaryoblastic leukemia (non-DS-AMKL), we performed transcriptome sequencing on diagnostic blasts from 14 pediatric patients and validated our findings in a recurrency/validation cohort consisting of 34 pediatric and 28 adult AMKL leukemia samples. Our analysis identified a cryptic chromosome 16 inversion [inv(16)(p13.3q24.3)] in 27% of pediatric cases, which encodes a CBFA2T3-GLIS2 fusion protein. Expression of CBFA2T3-GLIS2 in Drosophila and murine hematopoietic cells induced bone morphogenic protein (BMP) signaling, and resulted in a marked increase in the self-renewal capacity of hematopoietic progenitors. These data suggest that expression of CBFA2T3-GLIS2 directly contributes to leukemogenesis.","abstract":"To define the mutation spectrum in non-Down syndrome acute megkaryoblastic leukemia (non-DS-AMKL), we performed transcriptome sequencing on diagnostic blasts from 14 pediatric patients and validated our findings in a recurrency/validation cohort consisting of 34 pediatric and 28 adult AMKL leukemia samples. Our analysis identified a cryptic chromosome 16 inversion [inv(16)(p13.3q24.3)] in 27% of pediatric cases, which encodes a CBFA2T3-GLIS2 fusion protein. Expression of CBFA2T3-GLIS2 in Drosophila and murine hematopoietic cells induced bone morphogenic protein (BMP) signaling, and resulted in a marked increase in the self-renewal capacity of hematopoietic progenitors. These data suggest that expression of CBFA2T3-GLIS2 directly contributes to leukemogenesis.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-10-19T18:36:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000380","title":"GEenetic landscape of hypodiploid acute lymphoblastic leukemia","description":"Hypodiploid acute lymphoblastic leukemia (ALL) is an aggressive leukemia characterized by aneuploidy and poor outcome. The genetic basis of hypodiploid ALL is unknown. Here, using complementary genome-wide profiling approaches, we show that hypodiploid ALL comprises two subtypes that differ in the severity of aneuploidy, transcriptional profile and submicroscopic genetic alterations. Near haploid cases with 24-31 chromosomes frequently harbor alterations targeting receptor tyrosine kinase- and Ras signaling (71%) and IKZF3 (AIOLOS; 13%). In contrast, low hypodiploid ALL cases with 32-39 chromosomes are characterized by TP53 alterations, almost half of which are present in non-tumor cells, and have alterations of IKZF2 (HELIOS; 53%) and RB1 (41%). Both near haploid and low hypodiploid tumors exhibit activation of Ras and PI3K signaling pathways, and are sensitive to PI3K inhibition, indicating that these drugs should be explored as a new therapeutic strategy for this frequently lethal form of leukemia.","abstract":"Hypodiploid acute lymphoblastic leukemia (ALL) is an aggressive leukemia characterized by aneuploidy and poor outcome. The genetic basis of hypodiploid ALL is unknown. Here, using complementary genome-wide profiling approaches, we show that hypodiploid ALL comprises two subtypes that differ in the severity of aneuploidy, transcriptional profile and submicroscopic genetic alterations. Near haploid cases with 24-31 chromosomes frequently harbor alterations targeting receptor tyrosine kinase- and Ras signaling (71%) and IKZF3 (AIOLOS; 13%). In contrast, low hypodiploid ALL cases with 32-39 chromosomes are characterized by TP53 alterations, almost half of which are present in non-tumor cells, and have alterations of IKZF2 (HELIOS; 53%) and RB1 (41%). Both near haploid and low hypodiploid tumors exhibit activation of Ras and PI3K signaling pathways, and are sensitive to PI3K inhibition, indicating that these drugs should be explored as a new therapeutic strategy for this frequently lethal form of leukemia.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-10-19T18:38:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000381","title":"Whole-genome sequencing analysis of low-grade astrocytomas within the ICGC PedBrain Tumor Project","description":"In order to investigate the full range of genetic alterations contributing to the tumourigenesis of low-grade astrocytoma, we have conducted a next-generation sequencing-based analysis on a large series of matched tumor-normal pairs. This study, conducted by the International Cancer Genome Consortium PedBrain Tumor Project (ICGC PedBrain, http://www.pedbraintumor.org/), has revealed multiple new insights into the biological basis of this tumor entity.","abstract":"In order to investigate the full range of genetic alterations contributing to the tumourigenesis of low-grade astrocytoma, we have conducted a next-generation sequencing-based analysis on a large series of matched tumor-normal pairs. This study, conducted by the International Cancer Genome Consortium PedBrain Tumor Project (ICGC PedBrain, http://www.pedbraintumor.org/), has revealed multiple new insights into the biological basis of this tumor entity.","study_type":"Whole Genome Sequencing","pubmed_ids":[23817572],"external_links":null,"is_released":true,"released_date":"2012-10-22T13:27:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000382","title":"Transcriptional_profiling_of_tauopathies_in_human_IPS_derived_neurons","description":"This project is a pilot study, in collaboration with Maria Grazia Spillantini and Mariangela Iovino (Cambridge Centre for Brain Repair), to investigate the utility of IPS-derived neurons for the study of neurodegenerative disorders. Our aim is to characterise the transcriptional consequences of tauopathies using neurons derived from differentiated IPSCs as a model system. We will use IPS cells derived from six individuals, four with known mutations in the tau protein, 2 without. RNA will be extracted at Day 0 and Day 65 of differentiation by which time the neuronal tauopathy is apparent. RNA will be extracted and the transcriptome of each line characterised using RNAseq. We will then search for genes that are differentially expressed between the transcriptomes of individuals with tau mutations versus those in controls. My lab will analyse the RNAseq data, comparing both affected and controls and both time-points, to establish candidate genes. Darren Logan’s lab, along with our collaborators, will experimentally verify and further investigate these genes in additional lines and animal models. From this analysis we will generate a list of candidate genes that are differentially expressed between cases and controls. This study will not only help us understand the molecular basis of tauopathies, but also identify gene candidates for biomarkers of neurodegenerative disease. It will serve as a proof of principle for future planned studies into generating and transcriptomically analysing an allelic series of Tau mutations in IPSCs with a controlled genetic background.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Many neurodegenerative diseases are characterized by neuronal loss and intraneural accumulation of fibrillary material made of abnormal proteins. In Alzheimer’s disease for example, there are abundant extracellular amyloid plaques made of the β-amyloid peptide and intracellular neurofibrillary tangles (NFT) made of the microtubule-associated protein tau. Although it is clear that tau is linked to neurodegeneration the identity of the toxic species is still a matter of debate. The identification of Tau gene mutations in cases of frontotemporal dementia and parkinsonism linked to chromosome 17(FTDP-17T) has established a clear relationship between tau alterations and neurodegeneration. However, the mechanism leading from tau dysfunction/toxicity to cell death is not yet clear. Tau is amicrotubule- associated protein involved in microtubule assembly, stabilization and axonal transport. While in fetal brain only one tau isoform is present, in human adult brain there are 6 different tau isoforms that are produced from alternative splicing of one gene present in chromosome 17. Current experimental models for the in vitro study of tau and its pathology include animal models that often do not recapitulate the tau pattern of expression observed in adult human brain.Many neurodegenerative diseases are characterized by neuronal loss and intraneural accumulation of fibrillary material made of abnormal proteins. In Alzheimer’s disease for example, there are abundant extracellular amyloid plaques made of the β-amyloid peptide and intracellular neurofibrillary tangles (NFT) made of the microtubule-associated protein tau. Although it is clear that tau is linked to neurodegeneration the identity of the toxic species is still a matter of debate. The identification of Tau gene mutations in cases of frontotemporal dementia and parkinsonism linked to chromosome 17(FTDP-17T) has established a clear relationship between tau alterations and neurodegeneration. However, the mechanism leading from tau dysfunction/toxicity to cell death is not yet clear. Tau is amicrotubule- associated protein involved in microtubule assembly, stabilization and axonal transport. While in fetal brain only one tau isoform is present, in human adult brain there are 6 different tau isoforms that are produced from alternative splicing of one gene present in chromosome 17. Current experimental models for the in vitro study of tau and its pathology include animal models that often do not recapitulate the tau pattern of expression observed in adult human brain.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-10-23T16:07:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000383","title":"The genomic landscape of large and small tumors in early-onset prostate cancer patients","description":"This study characterizes the genomic landscape of prostate cancer (PCA) cells in patients below or at the age of 50 years. Tumors of such early onset patients already show a broad spectrum of sizes. To test if the size differences are indicative of special cancer subgroups, we sequenced the genome of the tumor cells and matched control samples from blood.","abstract":"This study characterizes the genomic landscape of prostate cancer (PCA) cells in patients below or at the age of 50 years. Tumors of such early onset patients already show a broad spectrum of sizes. To test if the size differences are indicative of special cancer subgroups, we sequenced the genome of the tumor cells and matched control samples from blood.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-10-24T12:01:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000384","title":"Oulu_Dyslipidemia_families","description":"These samples include exome sequences of family members with dyslipidemias from northern Finnish origin.","abstract":"These samples include exome sequences of family members with dyslipidemias from northern Finnish origin.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-10-25T14:28:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000385","title":"Crohn_s_Exome_Sequencing","description":"The aim is to find rare variants of intermediate penetrance in those at risk of Crohn's disease","abstract":"There is substantial evidence that rare variants of intermediate penetrance affect risk for Crohn's disease (e.g. established NOD2 mutations, unexplained genetic variance, families with many affected individuals). Next generation sequencing provides the first opportunity to attempt to map these variants in families. Several members from three multiplex families will have whole-exome pulldown and Illumina sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-10-25T14:29:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000386","title":"Paroxysmal_neurological_Disorders","description":"We are sequencing the exomes of patients with paroxysmal neurological disorders mainly focusing on migraine and epilepsy. Cases are collected from performance sites of members of the International Headache Genetics consortium and EuroEPINOMICS. Most cases have a strong family history. The study sample will include both cases and controls.","abstract":"We are sequencing the exomes of patients with paroxysmal neurological disorders mainly focusing on migraine and epilepsy. Cases are collected from performance sites of members of the International Headache Genetics consortium and EuroEPINOMICS. Most cases have a strong family history. The study sample will include both cases and controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-10-29T09:46:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000387","title":"Susceptibility_genes_for_the_development_of_SLE_during_treatment_of_IBD","description":"A potential and very serious side effect of treating IBD with antiTNFa therapies (the currentgold standard) is the development of systemic lupus erythematosis (SLE). This side effect israre and unpredictable. Out of several thousand cases having received treatment, theUniversity of Calgary have accumulated 12 individuals with full phenotyping and novelserological antibody discovery panel data. We propose to exome sequence these samples inan effort to identify rare highly-penetrant variants that could be underlying this severephenotype.","abstract":"A potential and very serious side effect of treating IBD with antiTNFa therapies (the currentgold standard) is the development of systemic lupus erythematosis (SLE). This side effect israre and unpredictable. Out of several thousand cases having received treatment, theUniversity of Calgary have accumulated 12 individuals with full phenotyping and novelserological antibody discovery panel data. We propose to exome sequence these samples inan effort to identify rare highly-penetrant variants that could be underlying this severephenotype.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-10-29T14:27:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000388","title":"Whole_exome_sequencing_of_young_onset_Primary_Sclerosing_Cholangitis","description":"Primary sclerosing chloangitis is a rare autoimmune disease of the liver (prevalence =10/100,000) with a mean age of onset of 40 years. We are currently undertaking GWASand immunochip experiments to identify loci underlying PSC susceptibility. Through ourcollaborators at the University of Calgary we have access to DNA from three parent-offspringtrios where the children required liver transplants due to PSC before the age of 9. These areextremely rare cases indeed and we believe that exome-sequencing represents a powerfulmeans of identifying the causal mutation underlying this severe phenotype.","abstract":"Primary sclerosing chloangitis is a rare autoimmune disease of the liver (prevalence =10/100,000) with a mean age of onset of 40 years. We are currently undertaking GWASand immunochip experiments to identify loci underlying PSC susceptibility. Through ourcollaborators at the University of Calgary we have access to DNA from three parent-offspringtrios where the children required liver transplants due to PSC before the age of 9. These areextremely rare cases indeed and we believe that exome-sequencing represents a powerfulmeans of identifying the causal mutation underlying this severe phenotype.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-10-29T16:34:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000389","title":"Whole exome sequencing of virus-associated HCC","description":"To understand comprehensive combinations of molecular alterations and seek for potential therapeutic targets/pathways in virus-associated HCC, we have conducted a whole exome sequencing (in-solution capturing all human coding exons) of 150 pairs of HCC cases.","abstract":"To understand comprehensive combinations of molecular alterations and seek for potential therapeutic targets/pathways in virus-associated HCC, we have conducted a whole exome sequencing (in-solution capturing all human coding exons) of 150 pairs of HCC cases.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-10-31T10:07:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000390","title":"Targeted_gene_fusion_sequencing__Fus_seq__in_mesothelioma","description":"This is a small pilot data set to test the feasibility of cDNA exomes across 1200 cancer cell line panel. cDNA exomes or Fus-seq is further explained in this studies Abstract.","abstract":"Fus-seq is a deep sequencing method for the precise identification of novel fusion genes in cancer. This protocol involves the capture and enrichment of transcripts during mRNA library preparation, followed by Illumina sequencing. In brief, double-stranded cDNA is prepared from total RNA and used in library preparation prior to exon capture with Agilent baits. The enrichment is performed using a set of baits designed to be complementary to all exons in the protein-coding portion of the human genome (Agilent SureSelect Human All Exon 50MB) and will thus identify any fusion transcripts contained in 21,416 protein-coding genes. To our knowledge, Fus-seq is the highest resolution approach available for the discovery of coding fusion transcripts. Fus-seq offers a number of additional advantages. First, it is amenable to high-throughput. Second, it uses the starting material (total RNA) in a more efficient manner, and therefore requires one third less sequencing than conventional RNA-seq. Ultimately, we propose to use Fus-seq to rapidly discover all mRNA fusion gene transcripts in a large set of cancer cell lines. A subset of fusion transcripts will be validated independently by targeted PCR sequencing to define the sensitivity and specificity of the technique.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-10-31T12:24:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000391","title":"Genetic_and_Epigenetic_Comparative_Characterizations_ofMegakaryocytes_derived_from_Human_Primary_blood_and_induced_Pluripotent_Stem_Cells","description":"DNA samples are purified from megakaryocytes derived from PB, CB and hiPSC.  The chromatin samples arethen immunoprecipitated for the following histone modification markers namely H3K4me1, H3K27ac and H3K27me3 , and followed by next generation sequencing.Genome wide chromatin modification analysis will probe into the epigenetic markers of intercell-line variability and those thatleads to high efficiency of MK production using the forward reprogramming of hiPSC.  Comparative ChiP-seq analysis will further probe the functional equivalence between MKs derived from human primary blood and hiPSC.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This study will combine high-throughput genomic and epigenetic analyses within emerging initiatives based on human induced pluripotent stem cell (hiPSC) technology to characterise key regulatory steps of differentiation, proliferation and fate determination in the human haematopoietic system, and to inform their application in regenerative medicine.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000392","title":"Low_coverage_whole_genome_sequencing_of_samples_from_the__Cretan_Greek_isolate_collection_HELIC_MANOLIS","description":"Whole-genome sequencing at 1x of samples from the Cretan Greek isolate collection HELIC-MANOLIS. Genome-wide association studies of complex traits have been successful in identifying common variant associations, but a substantial heritability gap remains. The field of complex trait genetics is shifting towards the study of low frequency and rare variants, which are hypothesised to have larger effects. The study of these variants can be empowered by focusing on isolated populations, in which rare variants may have increased in frequency and linkage disequilibrium tends to be extended. This work focuses on an isolated population from Crete, Greece. Sequencing is very efficient in isolated populations, because variants found in a few samples will be shared by others in extended haplotype contexts, supporting accurate imputation.","abstract":"Whole-genome sequencing at 1x of samples from the Cretan Greek isolate collection HELIC-MANOLIS. Genome-wide association studies of complex traits have been successful in identifying common variant associations, but a substantial heritability gap remains. The field of complex trait genetics is shifting towards the study of low frequency and rare variants, which are hypothesised to have larger effects. The study of these variants can be empowered by focusing on isolated populations, in which rare variants may have increased in frequency and linkage disequilibrium tends to be extended. This work focuses on an isolated population from Crete, Greece. Sequencing is very efficient in isolated populations, because variants found in a few samples will be shared by others in extended haplotype contexts, supporting accurate imputation.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-11-01T15:41:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000393","title":"Whole-genome-Sequencing of adult medulloblastoma","description":"Brain tumors constitute the childhood tumors with the highest mortality rates and survival is often associated with severe long-term sequelae due to intensive multimodal treatment regimens. Thus, the PedBrainTumor network aims at the identification of robust biomarkers for clinical management and novel molecular targets for therapeutic interventions. Using massively parallel whole-genome sequencing, and transcriptome and methylome sequencing for subsets of cases, we aim to decipher the molecular causes of medulloblastoma as well as low-grade astrocytoma, and to identify markers to stratify patients for specialized treatment. As the PedBrain network is affiliated with clinical trials in medulloblastoma and pilocytic astrocytoma, validation cohorts for the translation of key findings into clinical settings are readily available.","abstract":"Brain tumors constitute the childhood tumors with the highest mortality rates and survival is often associated with severe long-term sequelae due to intensive multimodal treatment regimens. Thus, the PedBrainTumor network aims at the identification of robust biomarkers for clinical management and novel molecular targets for therapeutic interventions. Using massively parallel whole-genome sequencing, and transcriptome and methylome sequencing for subsets of cases, we aim to decipher the molecular causes of medulloblastoma as well as low-grade astrocytoma, and to identify markers to stratify patients for specialized treatment. As the PedBrain network is affiliated with clinical trials in medulloblastoma and pilocytic astrocytoma, validation cohorts for the translation of key findings into clinical settings are readily available.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-11-07T08:20:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000394","title":"Genome-wide mutation analysis of germinal-center B-cell derived lymphomas within the ICGC MMML-Seq Consortium","description":"Germinal-center B-cell derived lymphomas (GCB-lymphomas) are the most common B-cell lymphomas in children and adults, with Burkitt Lymphomas (BL) predominating in childhood and follicular lymphoma (FL) and diffuse large B-cell lymphomas (DLBCL) predominating in older age groups. The cell-of-origin in all these lymphomas is supposed to be a germinal center B-cell and transformation of FL in DLBCL or intermediate DLBCL/BL (intL) can occur. In the framework of the German ICGC MMML-Seq we are currently exploring sequencing data of GCB-lymphomas and paired normal controls as well as normal B-cell subsets separated by FACS. This includes whole genome, transcriptome, miRNAome and whole methylome datasets.","abstract":"Germinal-center B-cell derived lymphomas (GCB-lymphomas) are the most common B-cell lymphomas in children and adults, with Burkitt Lymphomas (BL) predominating in childhood and follicular lymphoma (FL) and diffuse large B-cell lymphomas (DLBCL) predominating in older age groups. The cell-of-origin in all these lymphomas is supposed to be a germinal center B-cell and transformation of FL in DLBCL or intermediate DLBCL/BL (intL) can occur. In the framework of the German ICGC MMML-Seq we are currently exploring sequencing data of GCB-lymphomas and paired normal controls as well as normal B-cell subsets separated by FACS. This includes whole genome, transcriptome, miRNAome and whole methylome datasets.","study_type":"Other","pubmed_ids":[24139898],"external_links":null,"is_released":true,"released_date":"2012-11-08T10:18:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000395","title":"Pancreatic Cancer Sequencing Initiative OICR","description":"Pancreatic Cancer Sequencing Initiative for the International Cancer Genome Consortium at the Ontario Institute for Cancer Research.","abstract":"Pancreatic Cancer Sequencing Initiative for the International Cancer Genome Consortium at the Ontario Institute for Cancer Research.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-11-19T14:34:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000396","title":"Genetic_and_Epigenetic_Comparative_Characterizations_ofMegakaryocytes_derived_from_Human_Primary_blood_and_induced_Pluripotent_Stem_Cells","description":"RNA samples are purified from megakaryocytes derived from PB, CB and hiPSC.  Genome wide transcriptomic analysis using high throughput RNA sequencing will probe into genetic markers of intercell-line variability and those thatleads to high efficiency of MK production using the forward reprogramming of hiPSC.  Comparative transcriptomic analysis will further probe the functional equivalence between MKs derived from human primary blood and hiPSC.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This study will combine high-throughput genomic and epigenetic analyses within emerging initiatives based on human induced pluripotent stem cell (hiPSC) technology to characterise key regulatory steps of differentiation, proliferation and fate determination in the human haematopoietic system, and to inform their application in regenerative medicine.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000397","title":"Genome Landscape of High-Grade Serous Ovarian Cancer","description":"Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and\nstandard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To\nunderstand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline\nDNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory\ndisease. We observed several molecular events associated with acquired resistance, including multiple independent\nreversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an\nalteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux\npump MDR1.","abstract":"Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and\nstandard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To\nunderstand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline\nDNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory\ndisease. We observed several molecular events associated with acquired resistance, including multiple independent\nreversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an\nalteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux\npump MDR1.","study_type":"Other","pubmed_ids":[26017449],"external_links":null,"is_released":true,"released_date":"2012-11-27T03:14:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000398","title":"High_powered_complex_trait_association_mapping_through_whole_genome_sequencing_of_a_selected_subpopulation_of_the_INGI_Val_Borbera_genetic_isolate","description":"The VBSEQ project aims to combine available extensive genetic and phenotypic data to the latest high-throughput genome sequencing technology and ad hoc statistical analysis to identify new rare genetic variants underlying complex traits. Up to 100 Val Borbera samples will be sequenced to a 6x depth.","abstract":"The VBSEQ project aims to combine available extensive genetic and phenotypic data to the latest high-throughput genome sequencing technology and ad hoc statistical analysis to identify new rare genetic variants underlying complex traits. Up to 100 Val Borbera samples will be sequenced to a 6x depth.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-11-30T09:44:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000399","title":"Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma.","description":"follicular lymphoma (FL), the most common indolent non-Hodgkin’s lymphoma, remains incurable. A well-recognized complication of FL is its transformation to a diffuse large B-cell lymphoma (DLBCL)-morphology in a subset of patients, for which the clinical outcomes are poor. Recent genetic profiling and single case studies of donor-derived FL following stem cell transplantation had alluded to the putative existence of a ‘long lived’ tumor-initiating progenitor cell compartment from which successive disease events occurred. To chronicle the genetic changes associated with progression to transformation, we conducted whole-genome sequencing (WGS) of FL-tFL pairs and matched germline (GL) samples from six patients, a total of 20 genomes.","abstract":"follicular lymphoma (FL), the most common indolent non-Hodgkin’s lymphoma, remains incurable. A well-recognized complication of FL is its transformation to a diffuse large B-cell lymphoma (DLBCL)-morphology in a subset of patients, for which the clinical outcomes are poor. Recent genetic profiling and single case studies of donor-derived FL following stem cell transplantation had alluded to the putative existence of a ‘long lived’ tumor-initiating progenitor cell compartment from which successive disease events occurred. To chronicle the genetic changes associated with progression to transformation, we conducted whole-genome sequencing (WGS) of FL-tFL pairs and matched germline (GL) samples from six patients, a total of 20 genomes.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-12-02T20:55:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000400","title":"Integrative genomic analyses reveal androgen-driven somatic alteration landscape in early-onset prostate cancer","description":"Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with \"classical\" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in eleven tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of &gt;10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic \"androgen-type\" pathomechanism in EO-PCA.","abstract":"Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with \"classical\" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in eleven tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of &gt;10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic \"androgen-type\" pathomechanism in EO-PCA.","study_type":"Other","pubmed_ids":[23410972],"external_links":null,"is_released":true,"released_date":"2012-12-04T08:19:18+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000401","title":"Cancer_stem_cell_epigenome_profiling_in_mouse","description":"In spite of the advances in our knowledge of cancer biology, most cancers remain incurable with present therapies. Although current treatments can reduce tumour burden, relapse occurs in most cases. This was long attributed to incomplete tumour elimination, but an increasing body of research is showing that cancers, like normal tissues, contain their own stem cells, the so-called Cancer Stem Cells (CSCs), that share biomarkers with normal stem cells, proliferate indefinitely through a deregulated cellular self-renewal capacity and that are able to resist differentiation and apoptosis. Gaining insight into the genome of such cells is crucial for the understanding of cancer biology and for the design of appropriate therapeutic strategies that target these Cancer Stem Cells. In this project, we intend to characterize the epigenome of Cancer Stem Cells. This investigation will provide the basis for understanding for the first time what makes a cell a cancer stem cell.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"In order to characterise the epigenome of the cancer stem cells we will use MeDIP-seq to generate a methylation profile of newly successfully generated CSC-based mouse models of human tumours. The MeDIP-seq data will be analysed using MEDIPS.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000402","title":"Feasibility_of_targeted_capture_sequencing_in_FFPE_cancer_specimens_2","description":"Testing the feasibility of genome-scale sequencing in routinely collected formalin-fixed paraffin-embedded (FFPE) cancer specimens versus matched fresh-frozen samples using targeted pulldown capture prior to Illumina sequencing.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale. Being able to follow up studies in a larger cohort from FFPE samples would greatly increase the capacity of these studies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-12-06T10:41:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000403","title":"BASIS_Genome_Validation_Study","description":"Bespoke validation experiments will be performed on ER+ Breast Cancer cases to confirm the presence of mutations found in whole genome sequencing.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-12-14T11:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000404","title":"Myeloproliferative_Neoplasms__MPN__Exome_Validation_Study","description":"Experiments using targeted pulldown methods will be sequenced to validate findings in the exomes of patients with Myeloproliferative Neoplasms (MPN).","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-12-14T11:38:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000405","title":"Angiosarcoma_follow_up_study","description":"A bespoke targeted pulldown experiment will be performed on patients with Angiosarcoma. the resulting products will be sequenced to determine the prevalence of previously found mutations in these patients.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-12-14T11:55:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000406","title":"Myeloproliferative_Neoplasms__MPN__Targeted_Gene_Screen","description":"Pulldown experiments will be performed on a number of patients with Myeloproliferative Neoplasms (MPN). The pulldown will be a bespoke design targeting known mutations, this pulldown will be sequenced and analysed to inform prevalence of mutations and to inform to the possibility of use as a diagnostic tool.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-12-14T12:49:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000407","title":"Characterization_of_individual_foci_of_multicentric_multifocal_breast_cancer_using_targeted_next_generation_sequencing","description":"Multifocality or multicentricity in breast cancer may be defined as the presence of two or more tumor foci within a single quadrant of the breast or within different quadrants of the same breast, respectively. This original classification of the breast cancer as multicentric or multifocal was based on the assumption that cancers arising in the same quadrant were more likely to arise from the same ductal structures than those occurring in separate areas of the breast. The problem with these definitions is that the “quadrants” of the breast are arbitrary external designations, as no internal boundaries do exist. This project will therefore focus both on synchronous multifocal and multicentric tumors. The incidence of multifocal and multicentric breast cancers was reported to be between 13 and 75% depending on the definition used, the extent of the pathologic sampling of the breast and whether in situ disease is considered evidence of multicentricity (1). Although this incidence is variable, those figures show that it is a frequent phenomenon. Multiple (multifocal/multicentric) breast carcinomas, especially when occurring in the same breast, represent a real challenge for both pathologists and clinicians in terms of identifying the cellular origin and the best therapeutic management of the cancer. Multifocality or multicentricity has been associated with a number of more aggressive features including an increased rate of regional lymph node metastases and adverse patient outcome when compared with unifocal tumors (2-3), and a possible increased risk of local recurrence following breast conserving surgery (4). For the moment, the literature is divided on whether there is a corresponding impact on survival outcomes. Today, the current convention to stage and to treat multifocal and multicentric tumors is the classical tumor-node-metastasis (TNM) staging guidelines with which tumor size is assessed by the largest tumor focus without taking other foci of disease into consideration. If some papers, as the recent one from Lynch and colleagues, support the current staging convention (3), others, however, as Boyages et al. suggested that aggregate size and not the size of the largest lesion should be considered in order to refine the prognostic assessment of those tumors (5). On the top of that, the question whether multifocal/multicentric carcinomas are due to the spread of a single carcinoma throughout the breast or is due to multiple carcinomas arising simultaneously has been a matter of debate. Some studies suggested that multifocal breast cancer may result from either intramammary spread from a single primary tumor or multiple synchronous primary tumors; whereas others suggest that multiple breast carcinomas always arise from the same clone (6-8). Recently, Pietri and colleagues analyzed the biological characterization of a series of 113 multifocal/multicentric breast cancers (8) which were diagnosed over a 5-year period. The expression of estrogen (ER) and progesterone (PgR) receptors, Ki-67 proliferative index, expression of HER2 and tumor grading were prospectively determined in each tumor focus, and mismatches among foci were recorded. Mismatches in ER status were present in 5 (4.4%) cases and PgR in 18 (15.9%) cases. Mismatches in tumor grading were present in 21 cases (18.6%), proliferative index (Ki-67) in 17 (15%) cases and HER2 status in 11 (9.7%) cases. Interestingly, this heterogeneity among foci has led to 14 (12.4%) patients receiving different adjuvant treatments compared with what would have been indicated if we had only taken into account the biologic status of the primary tumor. This study therefore showed that differences in biological characteristics of multifocal/multicentric lesions play a crucial role in the adjuvant treatment decision making process. In this study, we will concentrate on a larger series of patients with multifocal invasive ductal breast cancer lesions. We aim at: 1. Evaluating the incidence of multifocality according to the different breast cancer molecular subtypes (ER-/HER2-, HER2+, ER+/HER2-). 2. Evaluating the incidence of multifocality in patients with hereditary breast cancer disease (presence of germline BRCA1 or BRCA2 mutations). Moreover, we would like to investigate if multifocal lesions with BRCA1 or BRCA2 mutations exhibit a characteristic combination of substitution mutation signatures and a distinctive profile of deletions as demonstrated recently by Nik-Zainal and colleagues (9). 3. Correlating multifocality with clinical information in order to define its influence on patients’ survival (DFS and OS). 4. Carrying high coverage targeted gene sequencing of driver cancer genes and genes whose mutation is of therapeutic importance in order to compare clinically-relevant genetic differences between several multifocal breast cancer lesions. 5. Evaluating the impact of the distance between the different lesions on the clinical outcome but also on the genetic differences. 6. Comparing gene expression patterns between several multifocal breast cancer lesions and correlate them with the results of the targeted genes screen. 7. Characterizing the genomic and transcriptomic status of cancer related genes in metastatic lesions (local recurrence, positive lymph node or distant metastatic sites) from the same multifocal invasive ductal breast cancer patients in order to evaluate the consequence of genomic and transcriptomic heterogeneity of multifocal lesions on metastatic lesions. Multiple (multifocal/multicentric) breast carcinomas, especially when occurring in the same breast, represent a real challenge for both pathologists and clinicians in terms of identifying the cellular origin and the best therapeutic choice. This project has the potential to identify genetic/transcriptomic differences existing between several lesions constituting multifocal breast cancers, which in the routine clinical practice are usually considered to be homogeneous among them. We foresee validating significant results in a larger series of patients and this, in turn, could have a remarkable impact on the treatment and clinical management of multifocal breast cancers. Indeed, we hope to provide some evidence whether or not each focus matters in multifocal and multicentric breast cancer to define the adequate therapeutic approach, especially in the context of targeted therapies. The work to be done at Sanger will be target gene screen pooling of 1400 samples.","abstract":"Multifocality or multicentricity in breast cancer may be defined as the presence of two or more tumor foci within a single quadrant of the breast or within different quadrants of the same breast, respectively. This original classification of the breast cancer as multicentric or multifocal was based on the assumption that cancers arising in the same quadrant were more likely to arise from the same ductal structures than those occurring in separate areas of the breast. The problem with these definitions is that the “quadrants” of the breast are arbitrary external designations, as no internal boundaries do exist. This project will therefore focus both on synchronous multifocal and multicentric tumors. The incidence of multifocal and multicentric breast cancers was reported to be between 13 and 75% depending on the definition used, the extent of the pathologic sampling of the breast and whether in situ disease is considered evidence of multicentricity (1). Although this incidence is variable, those figures show that it is a frequent phenomenon. Multiple (multifocal/multicentric) breast carcinomas, especially when occurring in the same breast, represent a real challenge for both pathologists and clinicians in terms of identifying the cellular origin and the best therapeutic management of the cancer. Multifocality or multicentricity has been associated with a number of more aggressive features including an increased rate of regional lymph node metastases and adverse patient outcome when compared with unifocal tumors (2-3), and a possible increased risk of local recurrence following breast conserving surgery (4). For the moment, the literature is divided on whether there is a corresponding impact on survival outcomes. Today, the current convention to stage and to treat multifocal and multicentric tumors is the classical tumor-node-metastasis (TNM) staging guidelines with which tumor size is assessed by the largest tumor focus without taking other foci of disease into consideration. If some papers, as the recent one from Lynch and colleagues, support the current staging convention (3), others, however, as Boyages et al. suggested that aggregate size and not the size of the largest lesion should be considered in order to refine the prognostic assessment of those tumors (5). On the top of that, the question whether multifocal/multicentric carcinomas are due to the spread of a single carcinoma throughout the breast or is due to multiple carcinomas arising simultaneously has been a matter of debate. Some studies suggested that multifocal breast cancer may result from either intramammary spread from a single primary tumor or multiple synchronous primary tumors; whereas others suggest that multiple breast carcinomas always arise from the same clone (6-8). Recently, Pietri and colleagues analyzed the biological characterization of a series of 113 multifocal/multicentric breast cancers (8) which were diagnosed over a 5-year period. The expression of estrogen (ER) and progesterone (PgR) receptors, Ki-67 proliferative index, expression of HER2 and tumor grading were prospectively determined in each tumor focus, and mismatches among foci were recorded. Mismatches in ER status were present in 5 (4.4%) cases and PgR in 18 (15.9%) cases. Mismatches in tumor grading were present in 21 cases (18.6%), proliferative index (Ki-67) in 17 (15%) cases and HER2 status in 11 (9.7%) cases. Interestingly, this heterogeneity among foci has led to 14 (12.4%) patients receiving different adjuvant treatments compared with what would have been indicated if we had only taken into account the biologic status of the primary tumor. This study therefore showed that differences in biological characteristics of multifocal/multicentric lesions play a crucial role in the adjuvant treatment decision making process. In this study, we will concentrate on a larger series of patients with multifocal invasive ductal breast cancer lesions. We aim at: 1. Evaluating the incidence of multifocality according to the different breast cancer molecular subtypes (ER-/HER2-, HER2+, ER+/HER2-). 2. Evaluating the incidence of multifocality in patients with hereditary breast cancer disease (presence of germline BRCA1 or BRCA2 mutations). Moreover, we would like to investigate if multifocal lesions with BRCA1 or BRCA2 mutations exhibit a characteristic combination of substitution mutation signatures and a distinctive profile of deletions as demonstrated recently by Nik-Zainal and colleagues (9). 3. Correlating multifocality with clinical information in order to define its influence on patients’ survival (DFS and OS). 4. Carrying high coverage targeted gene sequencing of driver cancer genes and genes whose mutation is of therapeutic importance in order to compare clinically-relevant genetic differences between several multifocal breast cancer lesions. 5. Evaluating the impact of the distance between the different lesions on the clinical outcome but also on the genetic differences. 6. Comparing gene expression patterns between several multifocal breast cancer lesions and correlate them with the results of the targeted genes screen. 7. Characterizing the genomic and transcriptomic status of cancer related genes in metastatic lesions (local recurrence, positive lymph node or distant metastatic sites) from the same multifocal invasive ductal breast cancer patients in order to evaluate the consequence of genomic and transcriptomic heterogeneity of multifocal lesions on metastatic lesions. Multiple (multifocal/multicentric) breast carcinomas, especially when occurring in the same breast, represent a real challenge for both pathologists and clinicians in terms of identifying the cellular origin and the best therapeutic choice. This project has the potential to identify genetic/transcriptomic differences existing between several lesions constituting multifocal breast cancers, which in the routine clinical practice are usually considered to be homogeneous among them. We foresee validating significant results in a larger series of patients and this, in turn, could have a remarkable impact on the treatment and clinical management of multifocal breast cancers. Indeed, we hope to provide some evidence whether or not each focus matters in multifocal and multicentric breast cancer to define the adequate therapeutic approach, especially in the context of targeted therapies. The work to be done at Sanger will be target gene screen pooling of 1400 samples.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-12-14T13:28:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000408","title":"Targeted_sequencing_of_genes_recurrently_mutated_in_AML","description":"Background Massively parallel sequencing technology has transformed cancer genomics. It is now feasible, in a clinically relevant time-frame, for a clinically manageable cost, to screen DNA from patient tumours for mutations essentially genome-wide. The challenge for personalised medicine will be to increase the sample size to thousands or tens of thousands of well-characterised cases in order to attain sufficient statistical power to stratify patients accurately across the complexity and genomic heterogeneity expected for most of the common tumour types. Currently, whole genome sequencing on this scale is not feasible, and targeted sequencing of relevant portions of the genome will be required. Pilot data We have developed protocols for large-scale, multiplexed sequencing of 100-200 genes in thousands of samples. Essentially, using robotic technology, genomic DNA from the cancer specimen is processed into sequencing libraries with unique DNA barcodes, thereby allowing sequencing reads to be attributed to the sample they derive from. Currently, these sequencing libraries can be generated in a 96-well format using fully automated protocols, and we are exploring methods to expand this to a 384-well format. The sequencing libraries are pooled and hybridized to custom sets of RNA baits representing the genomic regions of interest. Sequencing of the pulled-down libraries is done in pools of 48-96 samples per lane of an Illumina Hi-Seq. This protocol is already implemented at the Sanger Institute. We have published proof that somatic mutations in novel cancer genes can be identified from exome-wide sequencing. In unpublished pilot data, we have established the feasibility of robotic library production, custom pull-down, and multiplexed sequencing of barcoded libraries for 100 known myeloid cancer genes across 760 myelodysplasia samples. Highlights of the data thus far analysed reveal that the coverage is remarkably even between samples; when 96 samples are run, average coverage per lane of sequencing is ~250, with 90-95% of targeted exons covered by &gt;25 reads; known mutations can be discovered in the data set; and the protocol is amenable to whole genome amplified DNA. The bioinformatic algorithms for identification of substitutions and indels in pull-down data are well-established; we have pilot data proving that copy number changes, LOH and genomic rearrangements in specific regions of interest can also be identified by tiling of baits across the relevant loci. Proposal We propose to apply this methodology to 10000 samples from patients with AML enrolled in clinical trials over the last 10-20 years. Oncogenic point mutations and potentially genomic rearrangements will be identified, and linked to clinical outcome data, with a view to undertaking the following sorts of analyses: • Identification of co-occurrence, mutual exclusivity and clusters of driver mutations. • Correlation of prognosis with driver mutations and potentially gene-gene interactions • Exploration of genomic markers of drug response Ultimately, we would like to be in a position to release the mutation data together with matched clinical outcome data to genuine medical researchers via a controlled access approach, possibly within the COSMIC framework (www.sanger.ac.uk/genetics/CGP/cosmic/). The vision here is to generate a portal whereby a clinician faced with an AML patient and his / her mutational profile can obtain a ‘personalised’ prediction of outcome, together with a fair assessment of the uncertainty of the estimate. With a sufficient sample size, there would also be the potential to develop decision support algorithms for therapeutic choices based on such data.","abstract":"Background Massively parallel sequencing technology has transformed cancer genomics. It is now feasible, in a clinically relevant time-frame, for a clinically manageable cost, to screen DNA from patient tumours for mutations essentially genome-wide. The challenge for personalised medicine will be to increase the sample size to thousands or tens of thousands of well-characterised cases in order to attain sufficient statistical power to stratify patients accurately across the complexity and genomic heterogeneity expected for most of the common tumour types. Currently, whole genome sequencing on this scale is not feasible, and targeted sequencing of relevant portions of the genome will be required. Pilot data We have developed protocols for large-scale, multiplexed sequencing of 100-200 genes in thousands of samples. Essentially, using robotic technology, genomic DNA from the cancer specimen is processed into sequencing libraries with unique DNA barcodes, thereby allowing sequencing reads to be attributed to the sample they derive from. Currently, these sequencing libraries can be generated in a 96-well format using fully automated protocols, and we are exploring methods to expand this to a 384-well format. The sequencing libraries are pooled and hybridized to custom sets of RNA baits representing the genomic regions of interest. Sequencing of the pulled-down libraries is done in pools of 48-96 samples per lane of an Illumina Hi-Seq. This protocol is already implemented at the Sanger Institute. We have published proof that somatic mutations in novel cancer genes can be identified from exome-wide sequencing. In unpublished pilot data, we have established the feasibility of robotic library production, custom pull-down, and multiplexed sequencing of barcoded libraries for 100 known myeloid cancer genes across 760 myelodysplasia samples. Highlights of the data thus far analysed reveal that the coverage is remarkably even between samples; when 96 samples are run, average coverage per lane of sequencing is ~250, with 90-95% of targeted exons covered by &gt;25 reads; known mutations can be discovered in the data set; and the protocol is amenable to whole genome amplified DNA. The bioinformatic algorithms for identification of substitutions and indels in pull-down data are well-established; we have pilot data proving that copy number changes, LOH and genomic rearrangements in specific regions of interest can also be identified by tiling of baits across the relevant loci. Proposal We propose to apply this methodology to 10000 samples from patients with AML enrolled in clinical trials over the last 10-20 years. Oncogenic point mutations and potentially genomic rearrangements will be identified, and linked to clinical outcome data, with a view to undertaking the following sorts of analyses: • Identification of co-occurrence, mutual exclusivity and clusters of driver mutations. • Correlation of prognosis with driver mutations and potentially gene-gene interactions • Exploration of genomic markers of drug response Ultimately, we would like to be in a position to release the mutation data together with matched clinical outcome data to genuine medical researchers via a controlled access approach, possibly within the COSMIC framework (www.sanger.ac.uk/genetics/CGP/cosmic/). The vision here is to generate a portal whereby a clinician faced with an AML patient and his / her mutational profile can obtain a ‘personalised’ prediction of outcome, together with a fair assessment of the uncertainty of the estimate. With a sufficient sample size, there would also be the potential to develop decision support algorithms for therapeutic choices based on such data.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-12-14T13:57:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000409","title":"Chordoma_Sequencing_Project_Whole_Genome","description":"This is a continuation of the Chordoma Sequencing Project, prelim #G0175-122-CF. All cancers arise due to somatically acquired abnormalities in DNA sequence. Systematic sequencing of cancer genomes allows acquisition of complete catalogues of all classes of somatic mutation present in cancer. These mutation catalogues will allow identification of the somatically mutated cancer genes that are operative and characterise patterns of somatic mutation that may reflect previous exogenous and endogenous mutagenic exposures. In this application, we aim to perform whole genome sequencing on 10 chordoma matched genome pairs. The Chordoma Foundation will fund the RNA Sequencing/Methylation and SNP6 costs for this project while the whole genome and library sequencing will be covered under the CGP, 2012-2013 core WTSI internal funding. An additional sequencing of three cancer cell lines will be added to this work, financed by the Chordoma Foundation. In this project, the Chordoma foundation will pay for the additional costs of methylation, RNA Seq,","abstract":"This is a continuation of the Chordoma Sequencing Project, prelim #G0175-122-CF. All cancers arise due to somatically acquired abnormalities in DNA sequence. Systematic sequencing of cancer genomes allows acquisition of complete catalogues of all classes of somatic mutation present in cancer. These mutation catalogues will allow identification of the somatically mutated cancer genes that are operative and characterise patterns of somatic mutation that may reflect previous exogenous and endogenous mutagenic exposures. In this application, we aim to perform whole genome sequencing on 10 chordoma matched genome pairs. The Chordoma Foundation will fund the RNA Sequencing/Methylation and SNP6 costs for this project while the whole genome and library sequencing will be covered under the CGP, 2012-2013 core WTSI internal funding. An additional sequencing of three cancer cell lines will be added to this work, financed by the Chordoma Foundation. In this project, the Chordoma foundation will pay for the additional costs of methylation, RNA Seq,","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-12-14T14:24:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000410","title":"Chordoma_Sequencing_Project_RNAseq","description":"This is a continuation of the Chordoma Sequencing Project. All cancers arise due to somatically acquired abnormalities in DNA sequence. Systematic sequencing of cancer genomes allows acquisition of complete catalogues of all classes of somatic mutation present in cancer. These mutation catalogues will allow identification of the somatically mutated cancer genes that are operative and characterise patterns of somatic mutation that may reflect previous exogenous and endogenous mutagenic exposures. In this application, we aim to perform whole genome sequencing on 10 chordoma matched genome pairs. RNA Sequencing/Methylation and SNP6 and an additional sequencing of three cancer cell lines will be added to this work.","abstract":"This is a continuation of the Chordoma Sequencing Project. All cancers arise due to somatically acquired abnormalities in DNA sequence. Systematic sequencing of cancer genomes allows acquisition of complete catalogues of all classes of somatic mutation present in cancer. These mutation catalogues will allow identification of the somatically mutated cancer genes that are operative and characterise patterns of somatic mutation that may reflect previous exogenous and endogenous mutagenic exposures. In this application, we aim to perform whole genome sequencing on 10 chordoma matched genome pairs. RNA Sequencing/Methylation and SNP6 and an additional sequencing of three cancer cell lines will be added to this work.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2012-12-14T14:28:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000411","title":"The Cardiogenics study","description":"Cardiogenics is an European collaborative project, it started in January 2007 and was funded by the European Commission through its Sixth Framework Program (reference LSHM -CT-2006-037593) until 2011. It involved several laboratories from France (INSERM UMRS937), Germany (Lübeck University; Regensburg University), United Kingdom (the Welcome Trust Sanger Institute; University of Leicester) and Sweden (Uppsala University Hospital) and was coordinated by a management group composed of scientists from these different institutions. Under the coordination of the management group the laboratories are still developing projects using Cardiogenics data sets.  As part of the Cardiogenics project, RNA from monocytes and macrophages of 363 patients with coronary artery disease and 395 healthy individuals was prepared and genome-wide expression was assessed in both cell types using the Illumina HumanRef 8 v3 Beadchip .  The DNA of all these individuals was genotyped using the Human 610 Quad custom arrays. Both data sets were used to conduct eQTL analyses. A subsample of subjects included in an allelic-imbalance substudy were also genotyped using the Illumina Human Custom 1.2M array. Detailed description of these datasets can be found in Shah S et al. Circ Cardiovs Genet 2011; Rotival M et al. Plos Genet 2011, Almlöf et al. Plos One 2012 and Garnier S et al. Plos Genet 2013","abstract":"Cardiogenics is an European collaborative project, it started in January 2007 and was funded by the European Commission through its Sixth Framework Program (reference LSHM -CT-2006-037593) until 2011. It involved several laboratories from France (INSERM UMRS937), Germany (Lübeck University; Regensburg University), United Kingdom (the Welcome Trust Sanger Institute; University of Leicester) and Sweden (Uppsala University Hospital) and was coordinated by a management group composed of scientists from these different institutions. Under the coordination of the management group the laboratories are still developing projects using Cardiogenics data sets.  As part of the Cardiogenics project, RNA from monocytes and macrophages of 363 patients with coronary artery disease and 395 healthy individuals was prepared and genome-wide expression was assessed in both cell types using the Illumina HumanRef 8 v3 Beadchip .  The DNA of all these individuals was genotyped using the Human 610 Quad custom arrays. Both data sets were used to conduct eQTL analyses. A subsample of subjects included in an allelic-imbalance substudy were also genotyped using the Illumina Human Custom 1.2M array. Detailed description of these datasets can be found in Shah S et al. Circ Cardiovs Genet 2011; Rotival M et al. Plos Genet 2011, Almlöf et al. Plos One 2012 and Garnier S et al. Plos Genet 2013","study_type":"Transcriptome Analysis","pubmed_ids":[21965548,22144904],"external_links":null,"is_released":true,"released_date":"2013-01-07T12:03:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000412","title":"IDENTIFICATION OF SOMATIC MUTATIONS IN RELAPSED ACUTE MYELOID LEUKEMIA BY WHOLE-EXOME SEQUENCING AND ITS CLINICAL IMPLICATIONS","description":"Since most patients with acute myeloid leukemia (AML) die from progressive disease after relapse, mechanisms of relapse need to be identified. To address this issue, we utilized whole exome sequencing (WES) to distinguish missense mutations that contribute to AML progression. The study was designed to examine the molecular abnormalities of leukemic cells at initial diagnosis and at relapse in comparison with corresponding germ line control (saliva samples). The results of WES were analyzed by ADISCAN for ranking cancer variants and their gene-gene interactions. We identified relapse related somatic mutations in AML patients [n = 82 (samples paired with germ line control) and n=29 (serial samples at the time of diagnosis, complete remission and at relapse)]. Using this approach, we found unique 89 non-synonymous mutations at initial diagnosis and 93 non-synonymous mutations at relapse. Four different somatic mutations in FLT3 gene, which influence overall survival and one mutation in DCK gene, which controls the metabolism of Ara-C in AML cells were found at initial diagnosis. In WES analysis of AML patients having FLT3-ITD, we could not find any additional somatic mutations in FLT3 genes, but mutations in IDH1 and IDH2, which are associated with AML progression when mutated, were detected in two patients. We further screened mutated genes, associated with relapse, in 2 independent cohorts of 217 adult NK-AML patients at initial diagnosis and 87 adult NK-AML patients at relapse. In this way, our study will contribute to elucidate the mechanisms of AML progression and help identify therapeutic targets.","abstract":"Since most patients with acute myeloid leukemia (AML) die from progressive disease after relapse, mechanisms of relapse need to be identified. To address this issue, we utilized whole exome sequencing (WES) to distinguish missense mutations that contribute to AML progression. The study was designed to examine the molecular abnormalities of leukemic cells at initial diagnosis and at relapse in comparison with corresponding germ line control (saliva samples). The results of WES were analyzed by ADISCAN for ranking cancer variants and their gene-gene interactions. We identified relapse related somatic mutations in AML patients [n = 82 (samples paired with germ line control) and n=29 (serial samples at the time of diagnosis, complete remission and at relapse)]. Using this approach, we found unique 89 non-synonymous mutations at initial diagnosis and 93 non-synonymous mutations at relapse. Four different somatic mutations in FLT3 gene, which influence overall survival and one mutation in DCK gene, which controls the metabolism of Ara-C in AML cells were found at initial diagnosis. In WES analysis of AML patients having FLT3-ITD, we could not find any additional somatic mutations in FLT3 genes, but mutations in IDH1 and IDH2, which are associated with AML progression when mutated, were detected in two patients. We further screened mutated genes, associated with relapse, in 2 independent cohorts of 217 adult NK-AML patients at initial diagnosis and 87 adult NK-AML patients at relapse. In this way, our study will contribute to elucidate the mechanisms of AML progression and help identify therapeutic targets.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000413","title":"The_Transcriptome_of_PLX4032_resistance","description":"We have collected material from a patient who had BrafV600E mutant melanoma that wastreated with PLX4032. We have germline DNA from the patient and DNA and RNA fromdistinct lesions before and after treatment with PLX4032. We have transcriptome sequenced these samples to obtain a snap shot of the mechanisms of resistance that are operative.","abstract":"We have collected material from a patient who had BrafV600E mutant melanoma that wastreated with PLX4032. We have germline DNA from the patient and DNA and RNA fromdistinct lesions before and after treatment with PLX4032. We have transcriptome sequenced these samples to obtain a snap shot of the mechanisms of resistance that are operative.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-01-15T11:57:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000414","title":"Methylation_analysis_in_GM01240___GM01247","description":"DNA methylation is one of the most studied epigenetic marks in the human genome, with the result that the desire to map the human methylome has driven the development of several methods to map DNA methylation on a genomic scale. Our study presents the first comparison of two of these techniques - the targeted approach of the Infinium HumanMethylation450 BeadChip� with the immunoprecipitation and sequencing-based method, MeDIP-seq. Both methods were initially validated with respect to bisulfite sequencing as the gold standard and then assessed in terms of coverage, resolution and accuracy. The two methods were compared using DNA from two cell lines: GM01240 (XX) and GM01247 (XY), a sibling pair of European descent. The regions of the methylome that can be assayed by both methods and those that can only be assayed by one method were determined and the discovery of differentially methylated regions (DMRs) by both techniques was examined. Our results show that the Infinium HumanMethylation450 BeadChip� and MeDIP-seq show a good positive correlation (Spearman correlation of 0.68) on a genome-wide scale and can both be used successfully to determine differentially methylated loci in RefSeq genes, CpG islands, shores and shelves. MeDIP-seq however, allows a wider interrogation of methylated regions of the human genome, including thousands of non-RefSeq genes and repetitive elements, all of which may be of importance in disease. In our study MeDIP-seq allowed the detection of 15,709 differentially methylated regions, nearly twice as many as the array-based method (8070), which may result in a more comprehensive study of the methylome.","abstract":"DNA methylation is one of the most studied epigenetic marks in the human genome, with the result that the desire to map the human methylome has driven the development of several methods to map DNA methylation on a genomic scale. Our study presents the first comparison of two of these techniques - the targeted approach of the Infinium HumanMethylation450 BeadChip� with the immunoprecipitation and sequencing-based method, MeDIP-seq. Both methods were initially validated with respect to bisulfite sequencing as the gold standard and then assessed in terms of coverage, resolution and accuracy. The two methods were compared using DNA from two cell lines: GM01240 (XX) and GM01247 (XY), a sibling pair of European descent. The regions of the methylome that can be assayed by both methods and those that can only be assayed by one method were determined and the discovery of differentially methylated regions (DMRs) by both techniques was examined. Our results show that the Infinium HumanMethylation450 BeadChip� and MeDIP-seq show a good positive correlation (Spearman correlation of 0.68) on a genome-wide scale and can both be used successfully to determine differentially methylated loci in RefSeq genes, CpG islands, shores and shelves. MeDIP-seq however, allows a wider interrogation of methylated regions of the human genome, including thousands of non-RefSeq genes and repetitive elements, all of which may be of importance in disease. In our study MeDIP-seq allowed the detection of 15,709 differentially methylated regions, nearly twice as many as the array-based method (8070), which may result in a more comprehensive study of the methylome.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001000415","title":"Analysis_of_resistance_to_PLX4032","description":"We have collected material from a patient who had BrafV600E mutant melanoma that wastreated with PLX4032. We have germline DNA from the patient and DNA and RNA fromdistinct lesions before and after treatment with PLX4032. We would like to exome sequencethese samples to gain a snap shot of the mechanisms of resistance that are operative.","abstract":"We have collected material from a patient who had BrafV600E mutant melanoma that wastreated with PLX4032. We have germline DNA from the patient and DNA and RNA fromdistinct lesions before and after treatment with PLX4032. We would like to exome sequencethese samples to gain a snap shot of the mechanisms of resistance that are operative.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-01-17T15:46:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000416","title":"Preeclampsia InterPregGen Consortium: Whole Genome Sequencing of 100 unrelated Uzbeks (DNA samples from the Institute of Immunology, Uzbek Academy of Sciences, Tashkent, Uzbekistan; Republic Specialized Scientific Practical Medical Centre of Obstetrics and Gynecology, Tashkent, Uzbekistan)","description":"Preeclampsia (PE) is a syndrome affecting pregnant mothers and fetus/babies characterised by hypertension and proteinuria, and is a leading cause of maternal and fetal death and of premature births worldwide. The InterPregGen Consortium was funded by a European Framework 7 (FP7) grant and grew out of the WTCCC3 GWAS comparing ~2000 UK PE mothers with ~6000 common UK controls. The EGAS00001000416 study data is whole genome sequencing of 100 unrelated Uzbeks in order to impute genotypes into PE cases and controls from Uzbekistan and to provide genetic data and infrastructure for future genetic studies in Uzbekistan and Central Asia more generally and to fill a gap in worldwide information as Central Asia is not adequately represented in available genomic data. This study is one component of the InterPregGen FP7 project. DNA samples for this component were collected by InterPregGen Consortium collaborators in Tashkent, Uzbekistan at the Institute of Immunology, Uzbek Academy of Sciences and at the Republic Specialized Scientific Practical Medical Centre of Obstetrics and Gynecology","abstract":"Preeclampsia (PE) is a syndrome affecting pregnant mothers and fetus/babies characterised by hypertension and proteinuria, and is a leading cause of maternal and fetal death and of premature births worldwide. The InterPregGen Consortium was funded by a European Framework 7 (FP7) grant and grew out of the WTCCC3 GWAS comparing ~2000 UK PE mothers with ~6000 common UK controls. The EGAS00001000416 study data is whole genome sequencing of 100 unrelated Uzbeks in order to impute genotypes into PE cases and controls from Uzbekistan and to provide genetic data and infrastructure for future genetic studies in Uzbekistan and Central Asia more generally and to fill a gap in worldwide information as Central Asia is not adequately represented in available genomic data. This study is one component of the InterPregGen FP7 project. DNA samples for this component were collected by InterPregGen Consortium collaborators in Tashkent, Uzbekistan at the Institute of Immunology, Uzbek Academy of Sciences and at the Republic Specialized Scientific Practical Medical Centre of Obstetrics and Gynecology","study_type":"Other","pubmed_ids":[33239696],"external_links":null,"is_released":true,"released_date":"2013-01-21T08:48:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000417","title":"Preeclampsia InterPregGen Consortium: Whole Genome Sequencing of 100 unrelated Kazakhs (DNA samples from the Scientific Center of Obstetrics, Gynecology and Perinatology, Almaty, Kazakhstan; Gulnara Svyatova, Principal Investigator","description":"Preeclampsia (PE) is a syndrome affecting pregnant mothers and fetus/babies characterised by hypertension and proteinuria, and is a leading cause of maternal and fetal death and of premature births worldwide. The InterPregGen Consortium was funded by a European Framework 7 (FP7) grant and grew out of the WTCCC3 GWAS comparing ~2000 UK PE mothers with ~6000 common UK controls. The EGAS00001000417 study data is whole genome sequencing of 100 unrelated Kazakhs in order to impute genotypes into PE cases and controls from Kazakhstan and to provide genetic data and infrastructure for future genetic studies in Kazakhstan and Central Asia more generally and to fill a gap in worldwide information as Central Asia is not adequately represented in available genomic data. This study is one component of the InterPregGen FP7 project. DNA samples for this component were collected by InterPregGen Consortium collaborators at the Scientific Center of Obstetrics, Gynecology and Perinatology, Almaty, Kazakhstan (Gulnara Svyatova, Principal Investigator)","abstract":"Preeclampsia (PE) is a syndrome affecting pregnant mothers and fetus/babies characterised by hypertension and proteinuria, and is a leading cause of maternal and fetal death and of premature births worldwide. The InterPregGen Consortium was funded by a European Framework 7 (FP7) grant and grew out of the WTCCC3 GWAS comparing ~2000 UK PE mothers with ~6000 common UK controls. The EGAS00001000417 study data is whole genome sequencing of 100 unrelated Kazakhs in order to impute genotypes into PE cases and controls from Kazakhstan and to provide genetic data and infrastructure for future genetic studies in Kazakhstan and Central Asia more generally and to fill a gap in worldwide information as Central Asia is not adequately represented in available genomic data. This study is one component of the InterPregGen FP7 project. DNA samples for this component were collected by InterPregGen Consortium collaborators at the Scientific Center of Obstetrics, Gynecology and Perinatology, Almaty, Kazakhstan (Gulnara Svyatova, Principal Investigator)","study_type":"Other","pubmed_ids":[33239696],"external_links":null,"is_released":true,"released_date":"2013-01-21T08:48:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000418","title":"BLUEPRINT Bisulfite-seq (CNAG)","description":"Bisulfite-Seq","abstract":"Bisulfite-Seq","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-01-22T11:22:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000419","title":"Ewings_Sarcoma_RNA_seq_drug_sensitivity","description":"Illumina RNA-Seq will be performed on four Ewing’s sarcoma cell lines and two control cell lines. RNA was extracted from all the lines using a basic Trizol extraction protocol.","abstract":"Cancer is driven by mutation. Using Illumina massively parallel RNA sequencing technology, we aim to sequence the entire transcriptome of four Ewing’s sarcoma cell lines, and two control cell lines. This project will give unprecedented insights into gene expression levels, alternative splicing, fusions events and gene networks associated with Ewing’s sarcoma development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-01-28T13:58:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000420","title":"Breast_Cancer_FRT_RNA_seq","description":"We propose to definitively characterise the somatic genetics of ER+ve, HER2-ve breast cancer through generation of comprehensive catalogues of somatic mutations in breast cancer cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes/transcriptomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-01-28T14:00:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000421","title":"Paroxysmal_Neurological_Disorders___rare_epilepsies","description":"We are sequencing the exomes of patients with paroxysmal neurological disorders mainly focusing on migraine and epilepsy. Cases are collected from performance sites of members of  EuroEPINOMICS. Most cases have a strong family history. The study sample will include both cases and controls.","abstract":"We are sequencing the exomes of patients with paroxysmal neurological disorders mainly focusing on migraine and epilepsy. Cases are collected from performance sites of members of  EuroEPINOMICS. Most cases have a strong family history. The study sample will include both cases and controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-01-30T13:52:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000422","title":"ChIP_Seq_of_different_histone_modifications_in_human_primary_megakaryocytes_and_erythroblasts_and_in_a_human_megakaryocytic_cell_line__CHRF__","description":"Study of the transcription factor NF-E2 important for hematopoiesis in human megakaryocytes and erythroblasts as well as study of histone marks in human megakaryocytic and erythroblastic cells and cell lines.","abstract":"Study of the transcription factor NF-E2 important for hematopoiesis in human megakaryocytes and erythroblasts as well as study of histone marks in human megakaryocytic and erythroblastic cells and cell lines.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000423","title":"Validation_of_Exome_sequencing_of_S7RE_iPSC_lines","description":"PCR products were obtained from each target loci using genomic DNA from human iPS cells. Subsequently, PCR products are pooled and subjected to Illumina library preparation.  The library will be sequenced either by HiSeq or MiSeq. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Human induced pluripotent stem (iPS) cells could offer the prospect of autologous cell-replacement therapy to treat patients with genetic diseases. It is now known that human iPS cells carry tens of point mutations compared to the donor genome and often carry copy number changes. For safe use of human iPS cells in clinic, understanding the integrity of the iPS cell genome is important. We have analysed how these point mutations were introduced into the iPS cells genome by whole genome sequencing of iPS cells derived from monoclonal primary somatic cells. We found that 500-1000 SNVs were introduced during primary cell culture and reprogramming. We would like to perform deep sequencing of these SNVs in parental population to analyse the rate of culture-induced mutations","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-02-01T10:31:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000424","title":"DNaseI_seq_pilot","description":"This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The purpose of this pilot is to validate a DNaseI-seq protocol using a lymphoblastoid line. Once validated, the protocol will be used on iPS cells.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000425","title":"Congenital_Heart_Disease___Pilot","description":"This pilot study aims to generate pilot data to inform future study designs by resequencing the whole exomes of 10 unrelated individuals diagnosed with Congenital Heart Disease (CHD).","abstract":"This pilot study aims to generate pilot data to inform future study designs by resequencing the whole exomes of 10 unrelated individuals diagnosed with Congenital Heart Disease (CHD).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-02-04T15:42:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000426","title":"Triple_Negative_Breast_Cancer_Whole_Genome_Validations","description":"We propose to definitively characterise the somatic genetics of Triple negative breast cancer through generation of comprehensive catalogues of somatic mutations in 500 cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses. This study will use a bespoke bait set to pulldown regions of interest found in whole genome sequencing to validate mutations found.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-02-05T11:43:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000427","title":"Prostate_Cancer_Whole_Genome_Validations","description":"We propose to definitively characterise the somatic genetics of Prostate cancer through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing. This study will aim to validate the findings of the whole genome study by re-sequencing regions of interest using a bespoke pulldown bait. See ICGC website for more information: http://icgc.org/icgc/cgp/70/508/71331","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-02-05T12:05:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000428","title":"Neoadjuvant_Breast_Cancer_Validations","description":"This study aims to re-sequence findings from whole genome studies using a bespoke pulldown method to validate mutations in those genomes sequenced.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-02-05T12:18:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000429","title":"Whole_genome_sequence_of__third_generation_family_member__SFHS_","description":"Previously we performed deep WGS on 6 parents and 13 children from 3 large families from the Scottish Family Health Study to identify de novo mutations. This prelim is cover the additional sequencing of one grandchild from one of these three families. The inclusion of a third generation individual will provide additional experimental validation for the de novo mutations found in the initial trio. As in the previous study, the DNA will be WGS to a depth of approximately 25X to achieve this purpose.","abstract":"Previously we performed deep WGS on 6 parents and 13 children from 3 large families from the Scottish Family Health Study to identify de novo mutations. This prelim is cover the additional sequencing of one grandchild from one of these three families. The inclusion of a third generation individual will provide additional experimental validation for the de novo mutations found in the initial trio. As in the previous study, the DNA will be WGS to a depth of approximately 25X to achieve this purpose.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-02-06T08:55:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000430","title":"Validation_of_AML_Mutational_Screening","description":"We recently worked-up a pulldown protocol for studying 21 genes recurrently mutated in AML (Study1770). Our manuscript is currently under revision and to address the reviewers' comments we need to validate some mutations by re-sequencing. In this add-on study we will be using PCR followed by MiSeq for this purpose.","abstract":"2.9 per 100,000, AML is currently the commonest myeloid malignancy in Europe, yet the two main therapeutic options for this disease, anthracyclines and purine analogues, have remained unchanged for over 20 years. Therapeutic advances rely heavily on an improved understanding of the molecular pathogenesis of AML and the development of rationally designed treatments.Whole genome sequencing has identified most of the recurrently occuring mutations in AML. Identification of the gene mutations in individual AMLs can help stratify patient treatment. We recently demonstrated that a bespoke Sureselect baitset can be used to capture mutations in nearly all of these genes (Study1770). We need to validate some mutations of the mutations identified by re-sequencing. In this add-on study we will be using PCR followed by MiSeq for this purpose.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-02-13T12:31:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000431","title":"iPS_ChIP_seq_pilot","description":"This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The purpose of this pilot is to validate a ChIP protocol alongside a viable processing protocol for hiPS. Once optimised, the process/protocol will be handed over to SCCP.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000432","title":"BLM_hiPSC_exon_analysis_","description":"This study will analyze the whole exons of genes in iPS cells from deficient Bloom's syndrome patient. Through this study, we can understand allelic variation and its relationship to phenotype. This study also aims to analyze genome wide mutations using N-ethyl-N-nitrosourea mutagenesis in Blm-deficient iPS cells.","abstract":"This study will analyze the whole exons of genes in iPS cells from deficient Bloom's syndrome patient. Through this study, we can understand allelic variation and its relationship to phenotype. This study also aims to analyze genome wide mutations using N-ethyl-N-nitrosourea mutagenesis in Blm-deficient iPS cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000433","title":"ICGC_Benchmarking_Exercise","description":"The main objective of this benchmark is the comparison of the full sequencing pipeline of different ICGC partners, including procedures, methods and performance of library preparation and whole-genome deep-sequencing. A secondary objective will be a follow-up comparison of data analysis pipelines for identification of germline and somatic variants subsequent to the results of the ICGC Somatic Variant Calling Pipeline Benchmark.","abstract":"The main objective of this benchmark is the comparison of the full sequencing pipeline of different ICGC partners, including procedures, methods and performance of library preparation and whole-genome deep-sequencing. A secondary objective will be a follow-up comparison of data analysis pipelines for identification of germline and somatic variants subsequent to the results of the ICGC Somatic Variant Calling Pipeline Benchmark.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-02-15T13:14:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000434","title":"Matched_Pair_Cell_Line_Tumour_RNAseq","description":"In this study we will sequence the transcriptome of Verified Matched Pair Cancer Cell line tumour samples. This will be married up to whole exome and whole genome sequencing data to establish a full catalog of the variations and mutations found.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-02-15T13:22:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000435","title":"Single_Cell_Targeted_Sequence_Capture","description":"This study is to ascertain whether it is feasible to extract single cell from a tumour, perform amplification, generate a library and sequence a targeted pulldown.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-02-15T13:43:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000436","title":"Lung_Multi_site_Targeted_Sequence_Capture","description":"DNA extracted from multiple biopsies taken from different areas of primary lung tumours will be subjected to targeted re-sequencing and analysed in order to assess intra-tumour heterogeneity with respect to mutations in a selection of cancer related genes.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-02-15T13:48:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000437","title":"Deep_sequencing_of_S7EPC_genome","description":"PCR products were obtained from each target loci using genomic DNA from human iPS cells. Subsequently, PCR products are pooled and subjected to Illumina library preparation.  The library will be sequenced either by HiSeq or MiSeq. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Human induced pluripotent stem (iPS) cells could offer the prospect of autologous cell-replacement therapy to treat patients with genetic diseases. It is now known that human iPS cells carry tens of point mutations compared to the donor genome and often carry copy number changes. For safe use of human iPS cells in clinic, understanding the integrity of the iPS cell genome is important. We have analysed how these point mutations were introduced into the iPS cells genome by whole genome sequencing of iPS cells derived from monoclonal primary somatic cells. We found that 500-1000 SNVs were introduced during primary cell culture and reprogramming. We would like to perform deep sequencing of these SNVs in parental population to analyse the rate of culture-induced mutations","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-02-18T11:17:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000438","title":"SOLiD 3/4 mate pair sequencing of hormone negative breast cancers focusing on structural rearrangements","description":"Background Chromosomal rearrangements in the form of deletions, insertions, inversions and translocations are frequently observed in breast cancer genomes, and a subset of these rearrangements may play a crucial role in tumorigenesis. To identify novel somatic chromosomal rearrangements, we determined the genome structures of 15 hormone-receptor negative breast tumors by long-insert mate pair massively parallel sequencing. Results We identified and validated 40 somatic structural alterations, including the recurring fusion between genes DDX10 and SKA3 and translocations involving the EPHA5 gene. Other rearrangements were found to affect genes in pathways involved in epigenetic regulation, mitosis and signal transduction, underscoring their potential role in breast tumorigenesis. RNA interference-mediated suppression of five candidate genes (DDX10, SKA3, EPHA5, CLTC and TNIK) led to inhibition of breast cancer cell growth. Moreover, downregulation of DDX10 in breast cancer cells lead to an increased frequency of apoptotic nuclear morphology. Conclusions Using whole genome mate pair sequencing and RNA interference assays, we have discovered a number of novel gene rearrangements in breast cancer genomes and identified DDX10, SKA3, EPHA5, CLTC and TNIK as potential cancer genes with impact on the growth and proliferation of breast cancer cells.","abstract":"Background Chromosomal rearrangements in the form of deletions, insertions, inversions and translocations are frequently observed in breast cancer genomes, and a subset of these rearrangements may play a crucial role in tumorigenesis. To identify novel somatic chromosomal rearrangements, we determined the genome structures of 15 hormone-receptor negative breast tumors by long-insert mate pair massively parallel sequencing. Results We identified and validated 40 somatic structural alterations, including the recurring fusion between genes DDX10 and SKA3 and translocations involving the EPHA5 gene. Other rearrangements were found to affect genes in pathways involved in epigenetic regulation, mitosis and signal transduction, underscoring their potential role in breast tumorigenesis. RNA interference-mediated suppression of five candidate genes (DDX10, SKA3, EPHA5, CLTC and TNIK) led to inhibition of breast cancer cell growth. Moreover, downregulation of DDX10 in breast cancer cells lead to an increased frequency of apoptotic nuclear morphology. Conclusions Using whole genome mate pair sequencing and RNA interference assays, we have discovered a number of novel gene rearrangements in breast cancer genomes and identified DDX10, SKA3, EPHA5, CLTC and TNIK as potential cancer genes with impact on the growth and proliferation of breast cancer cells.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000439","title":"Noninvasive prenatal molecular karyotyping from maternal plasma","description":"Fetal DNA is present in the plasma of pregnant women. Massively parallel sequencing of  maternal plasma DNA has been used to detect fetal trisomies 21, 18, 13 and selected sex  chromosomal aneuploidies noninvasively. Case reports describing the detection of fetal  microdeletions from maternal plasma using massively parallel sequencing have been reported.  However, these previous reports were either polymorphism-dependent or used statistical  analyses which were confined to one or a small number of selected parts of the genome. In  this report, we reported a procedure for performing noninvasive prenatal karyotyping at 3 Mb  resolution across the whole genome through the massively parallel sequencing of maternal  plasma DNA. This method has been used to analyze the plasma obtained from 6 cases. In 5  cases, fetal microduplications or microdeletions have been detected successfully from maternal  plasma. The two cases with fetal microduplications represented the first noninvasive prenatal  detection of such changes from maternal plasma. In the remaining case, the plasma DNA  sequencing result was consistent with the pregnant mother being a carrier of a microduplication.  Simulation analyses were performed for determining the number of plasma DNA molecules that  would need to be sequenced and aligned for enhancing the diagnostic resolution of noninvasive  prenatal karyotyping to 2 Mb and 1 Mb. In conclusion, noninvasive prenatal molecular  karyotyping from maternal plasma by massively parallel sequencing is feasible and would  enhance the diagnostic spectrum of noninvasive prenatal testing.","abstract":"Fetal DNA is present in the plasma of pregnant women. Massively parallel sequencing of  maternal plasma DNA has been used to detect fetal trisomies 21, 18, 13 and selected sex  chromosomal aneuploidies noninvasively. Case reports describing the detection of fetal  microdeletions from maternal plasma using massively parallel sequencing have been reported.  However, these previous reports were either polymorphism-dependent or used statistical  analyses which were confined to one or a small number of selected parts of the genome. In  this report, we reported a procedure for performing noninvasive prenatal karyotyping at 3 Mb  resolution across the whole genome through the massively parallel sequencing of maternal  plasma DNA. This method has been used to analyze the plasma obtained from 6 cases. In 5  cases, fetal microduplications or microdeletions have been detected successfully from maternal  plasma. The two cases with fetal microduplications represented the first noninvasive prenatal  detection of such changes from maternal plasma. In the remaining case, the plasma DNA  sequencing result was consistent with the pregnant mother being a carrier of a microduplication.  Simulation analyses were performed for determining the number of plasma DNA molecules that  would need to be sequenced and aligned for enhancing the diagnostic resolution of noninvasive  prenatal karyotyping to 2 Mb and 1 Mb. In conclusion, noninvasive prenatal molecular  karyotyping from maternal plasma by massively parallel sequencing is feasible and would  enhance the diagnostic spectrum of noninvasive prenatal testing.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-02-22T07:37:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000440","title":"Low_coverage_whole_genome_sequencing_of_samples_from_the_Greek_isolate_collection_HELIC_Pomak","description":"Whole-genome sequencing at 1x of samples from the Greek isolate collection HELIC-Pomak. Genome-wide association studies of complex traits have been successful in identifying common variant associations, but a substantial heritability gap remains. The field of complex trait genetics is shifting towards the study of low frequency and rare variants, which are hypothesised to have larger effects. The study of these variants can be empowered by focusing on isolated populations, in which rare variants may have increased in frequency and linkage disequilibrium tends to be extended. This work focuses on an isolated population from the Pomak villages in the north of Greece. Sequencing is very efficient in isolated populations, because variants found in a few samples will be shared by others in extended haplotype contexts, supporting accurate imputation.","abstract":"Whole-genome sequencing at 1x of samples from the Greek isolate collection HELIC-Pomak. Genome-wide association studies of complex traits have been successful in identifying common variant associations, but a substantial heritability gap remains. The field of complex trait genetics is shifting towards the study of low frequency and rare variants, which are hypothesised to have larger effects. The study of these variants can be empowered by focusing on isolated populations, in which rare variants may have increased in frequency and linkage disequilibrium tends to be extended. This work focuses on an isolated population from the Pomak villages in the north of Greece. Sequencing is very efficient in isolated populations, because variants found in a few samples will be shared by others in extended haplotype contexts, supporting accurate imputation.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000441","title":"Subclonal_analysis_in_S7RE2_and_S7RE14_iPS_cells","description":"PCR products were obtained from each target loci using genomic DNA from human iPS cells. Subsequently, PCR products are pooled and subjected to Illumina library preparation.  The library will be sequenced either by HiSeq or MiSeq. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Human induced pluripotent stem (iPS) cells could offer the prospect of autologous cell-replacement therapy to treat patients with genetic diseases. It is now known that human iPS cells carry tens of point mutations compared to the donor genome and often carry copy number changes. For safe use of human iPS cells in clinic, understanding the integrity of the iPS cell genome is important. We have analysed how these point mutations were introduced into the iPS cells genome by whole genome sequencing of iPS cells derived from monoclonal primary somatic cells. We found that 500-1000 SNVs were introduced during primary cell culture and reprogramming. We would like to perform deep sequencing of these SNVs in parental population to analyse the rate of culture-induced mutations","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-02-25T11:21:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000442","title":"Cell-type, allelic and genetic signatures in the human pancreatic beta cell transcriptome","description":"Pancreatic beta cells within the islets of Langerhans are centrally involved in the pathogenesis of both type 1 and type 2 diabetes. Describing the differentiated state of the human beta cell has been hampered so far by technical (low resolution microarrays) and biological limitations (whole islet preparations rather than isolated beta cells). We circumvent these by deep RNA sequencing of purified beta cells from 11 individuals, presenting here the first characterization of the human beta cell transcriptome. Additionally, we perform the first comparison of gene expression profiles between beta cells, whole islets (N=7) and beta cell depleted islet preparations (N=5), revealing thus beta cell specific expression signatures. Finally, we combine this with whole-genome sequencing data for 7 of our donors, describing here the first set of genetic variants controlling inter-individual variability in beta cell gene expression.","abstract":"Pancreatic beta cells within the islets of Langerhans are centrally involved in the pathogenesis of both type 1 and type 2 diabetes. Describing the differentiated state of the human beta cell has been hampered so far by technical (low resolution microarrays) and biological limitations (whole islet preparations rather than isolated beta cells). We circumvent these by deep RNA sequencing of purified beta cells from 11 individuals, presenting here the first characterization of the human beta cell transcriptome. Additionally, we perform the first comparison of gene expression profiles between beta cells, whole islets (N=7) and beta cell depleted islet preparations (N=5), revealing thus beta cell specific expression signatures. Finally, we combine this with whole-genome sequencing data for 7 of our donors, describing here the first set of genetic variants controlling inter-individual variability in beta cell gene expression.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001000443","title":"Epigenomic alterations define lethal CIMP-positive ependymomas of infancy","description":"Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.","abstract":"Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.","study_type":"Other","pubmed_ids":[24553142],"external_links":null,"is_released":true,"released_date":"2013-02-28T12:58:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000444","title":"Validation_of_SNVs_found_by_Exome_seq_in_S2_SF1___SF4_and__SF9_hiPSCs","description":"PCR products were obtained from each target loci using genomic DNA from human iPS cells. Subsequently, PCR products are pooled and subjected to Illumina library preparation.  The library will be sequenced either by HiSeq or MiSeq. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Human induced pluripotent stem (iPS) cells could offer the prospect of autologous cell-replacement therapy to treat patients with genetic diseases. It is now known that human iPS cells carry tens of point mutations compared to the donor genome and often carry copy number changes. For safe use of human iPS cells in clinic, understanding the integrity of the iPS cell genome is important. We have analysed how these point mutations were introduced into the iPS cells genome by whole genome sequencing of iPS cells derived from monoclonal primary somatic cells. We found that 500-1000 SNVs were introduced during primary cell culture and reprogramming. We would like to perform deep sequencing of these SNVs in parental population to analyse the rate of culture-induced mutations","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000446","title":"Passive and active DNA methylation and the interplay with genetic variation in gene regulation","description":"DNA methylation is an essential1 epigenetic mark whose role in gene regulation and its dependency on genomic sequence and environment are not yet fully understood2,3. In this study we provide novel insights into the mechanistic relationships between genetic variation, DNA methylation and transcriptome sequencing data in three different cell-types of the GenCord human population cohort4. We find that the association between DNA methylation and gene expression variation among individuals are likely due to different mechanisms from those establishing methylation-expression patterns during differentiation. Furthermore, cell-type differential DNA methylation may delineate a platform in which more local inter-individual changes may respond to or act in gene regulation. We show that unlike genetic regulatory variation, DNA methylation alone does not significantly drive allele specific expression.. Finally, inferred mechanistic relationships using genetic variation as well as correlations with TF abundance reveal both a passive and active role of DNA methylation to regulatory interactions influencing gene expression.","abstract":"DNA methylation is an essential1 epigenetic mark whose role in gene regulation and its dependency on genomic sequence and environment are not yet fully understood2,3. In this study we provide novel insights into the mechanistic relationships between genetic variation, DNA methylation and transcriptome sequencing data in three different cell-types of the GenCord human population cohort4. We find that the association between DNA methylation and gene expression variation among individuals are likely due to different mechanisms from those establishing methylation-expression patterns during differentiation. Furthermore, cell-type differential DNA methylation may delineate a platform in which more local inter-individual changes may respond to or act in gene regulation. We show that unlike genetic regulatory variation, DNA methylation alone does not significantly drive allele specific expression.. Finally, inferred mechanistic relationships using genetic variation as well as correlations with TF abundance reveal both a passive and active role of DNA methylation to regulatory interactions influencing gene expression.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001000447","title":"Germline Aberrations of PAX5 Cause Susceptibility to pre-B cell Acute Lymphoblastic Leukemia","description":"A novel heterozygous germline variant, c.547G>A (p.Gly183Ser), in the paired box protein encoding gene, PAX5, was found to segregate with disease in two unrelated kindreds with autosomal dominant pre-B cell acute lymphoblastic leukemia (ALL). Leukemic cells from both families exhibited 9p deletion, with loss-of-heterozygosity and retention of the mutant PAX5 allele at 9p13 . Two additional sporadic ALL cases with 9p loss demonstrated PAX5 Gly183 substitution in the leukemic cells. Functional analysis of the PAX5 germline variants demonstrated reduced transcriptional activity, as well as decreased interaction with Groucho-4. These data extend the role of PAX5 alterations in the pathogenesis of pre-B ALL, and implicate PAX5 in a novel syndrome of germline susceptibility to pre-B cell neoplasia.","abstract":"A novel heterozygous germline variant, c.547G&gt;A (p.Gly183Ser), in the paired box protein encoding gene, PAX5, was found to segregate with disease in two unrelated kindreds with autosomal dominant pre-B cell acute lymphoblastic leukemia (ALL). Leukemic cells from both families exhibited 9p deletion, with loss-of-heterozygosity and retention of the mutant PAX5 allele at 9p13 . Two additional sporadic ALL cases with 9p loss demonstrated PAX5 Gly183 substitution in the leukemic cells. Functional analysis of the PAX5 germline variants demonstrated reduced transcriptional activity, as well as decreased interaction with Groucho-4. These data extend the role of PAX5 alterations in the pathogenesis of pre-B ALL, and implicate PAX5 in a novel syndrome of germline susceptibility to pre-B cell neoplasia.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-03-11T14:50:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000449","title":"The landscape of somatic mutations in epigenetic regulators across 1000 pediatric cancer genomes","description":"To define the frequency and pattern of somatic mutations in epigenetic regulators in pediatric cancer, we sequenced 633 genes, encoding the majority of proteins involved in patterning the epigenome, in 1000 pediatric tumors spanning 21 different cancer subtypes. This analysis establishes an epigenetic landscape of pediatric cancer, which expands the knowledge for potential therapeutic targets and for developing personalized therapy.","abstract":"To define the frequency and pattern of somatic mutations in epigenetic regulators in pediatric cancer, we sequenced 633 genes, encoding the majority of proteins involved in patterning the epigenome, in 1000 pediatric tumors spanning 21 different cancer subtypes. This analysis establishes an epigenetic landscape of pediatric cancer, which expands the knowledge for potential therapeutic targets and for developing personalized therapy.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-03-12T20:14:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000451","title":"Plasma-Seq of patients with metastatic prostate cancer","description":"Study 1 In this study we analysed patients with metastatic prostate cancer to scan their tumor genomes noninvasively in plasma DNA. We wanted to make whole-genome analysis from plasma DNA amenable to clinical routine applications and developed an approach based on a benchtop high-throughput platform, i.e. Illuminas MiSeq instrument. We performed whole-genome sequencing from plasma at a shallow sequencing depth to establish a genome-wide copy number profile of the tumor at low costs within 2 days. The genome-wide profiling in the plasma of our patients revealed multiple copy number aberrations including those previously reported in prostate tumors, such as losses in 8p and gains in 8q. High-level copy number gains in the AR locus were observed in patients with CRPC but not with CSPC disease. We identified the TMPRSS2-ERG rearrangement associated 3-Mbp deletion on chromosome 21 and found corresponding fusion plasma fragments in these cases. In an index case multiregional sequencing of the primary tumor identified different copy number changes in each sector, suggesting multifocal disease. Our plasma analyses of this index case, performed 13 years after resection of the primary tumor, revealed novel chromosomal rearrangements, which were stable in serial plasma analyses over a 9 months period, which is consistent with the presence of one metastatic clone.  Our approach provides specific genomic signatures within 2 days which may therefore serve as “liquid biopsy”.","abstract":"Study 1 In this study we analysed patients with metastatic prostate cancer to scan their tumor genomes noninvasively in plasma DNA. We wanted to make whole-genome analysis from plasma DNA amenable to clinical routine applications and developed an approach based on a benchtop high-throughput platform, i.e. Illuminas MiSeq instrument. We performed whole-genome sequencing from plasma at a shallow sequencing depth to establish a genome-wide copy number profile of the tumor at low costs within 2 days. The genome-wide profiling in the plasma of our patients revealed multiple copy number aberrations including those previously reported in prostate tumors, such as losses in 8p and gains in 8q. High-level copy number gains in the AR locus were observed in patients with CRPC but not with CSPC disease. We identified the TMPRSS2-ERG rearrangement associated 3-Mbp deletion on chromosome 21 and found corresponding fusion plasma fragments in these cases. In an index case multiregional sequencing of the primary tumor identified different copy number changes in each sector, suggesting multifocal disease. Our plasma analyses of this index case, performed 13 years after resection of the primary tumor, revealed novel chromosomal rearrangements, which were stable in serial plasma analyses over a 9 months period, which is consistent with the presence of one metastatic clone.  Our approach provides specific genomic signatures within 2 days which may therefore serve as “liquid biopsy”.","study_type":"Other","pubmed_ids":[23561577],"external_links":null,"is_released":true,"released_date":"2013-03-13T10:35:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000453","title":"Identification of mutations and structural rearrangements in plasma DNA form metastatic prostate cancer patients","description":"In this study we analysed patients with metastatic prostate cancer to scan their tumor genomes noninvasively in plasma DNA. We enriched 1.3 Mbp of seven plasma DNAs (4 CRPC cases: CRPC1-3 and CRPC5; 3 CSPC cases: CSPC1-2 and CSPC4) including exonic sequences of 55 cancer genes and 38 introns of 18 genes, where fusion breakpoints have been described using Sure Select Custom DNA Kit.","abstract":"In this study we analysed patients with metastatic prostate cancer to scan their tumor genomes noninvasively in plasma DNA. We enriched 1.3 Mbp of seven plasma DNAs (4 CRPC cases: CRPC1-3 and CRPC5; 3 CSPC cases: CSPC1-2 and CSPC4) including exonic sequences of 55 cancer genes and 38 introns of 18 genes, where fusion breakpoints have been described using Sure Select Custom DNA Kit.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-03-13T10:45:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000455","title":"Whole genome bisufite sequencing of smoking and non-smoking mother-child pairsBisufite sequencing, RNA-seq and ChIP-Seq data of whole blood samples from smoking and non-smoking mothers and their children at gestation/birth and follow-up years.","description":"Whole-blood samples of 16 mother-child pairs with differing maternal smoking behaviour were bisulfite treated and sequenced with deep coverage to identify smoking-associated differentially methylated regions.RNA-sequencing and ChIP-sequencing of 4 chromatin marks complete the data set and allow for integrative analyses, functional region annotation and to study the impact of epigenetic changes on gene expression.Longitudinal data spanning several years provides the means to investigate the stability of observed differences of all data types.","abstract":"Whole-blood samples of 16 mother-child pairs with differing maternal smoking behaviour were bisulfite treated and sequenced with deep coverage to identify smoking-associated differentially methylated regions.RNA-sequencing and ChIP-sequencing of 4 chromatin marks complete the data set and allow for integrative analyses, functional region annotation and to study the impact of epigenetic changes on gene expression.Longitudinal data spanning several years provides the means to investigate the stability of observed differences of all data types.","study_type":"Epigenetics","pubmed_ids":[27013061],"external_links":null,"is_released":true,"released_date":"2013-03-15T13:43:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000458","title":"Whole_Genome_sequencing_of_individuals_from_Val_Borbera__Italy","description":"This study includes Phase 2 whole-genome sequencing data (at 4x depth)of 100 individuals from an Italian genetic isolate population (Val Borbera, abbreviated VBI) of the Italian Network of Genetic Isolates (INGI). The INGI-VBI_SEQ2 project aims to combine available extensive genetic and phenotypic data to the latest high-throughput genome sequencing technology and ad hoc statistical analysis to identify new rare genetic variants underlying complex traits.","abstract":"This study includes Phase 2 whole-genome sequencing data (at 4x depth)of 100 individuals from an Italian genetic isolate population (Val Borbera, abbreviated VBI) of the Italian Network of Genetic Isolates (INGI). The INGI-VBI_SEQ2 project aims to combine available extensive genetic and phenotypic data to the latest high-throughput genome sequencing technology and ad hoc statistical analysis to identify new rare genetic variants underlying complex traits.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-03-20T14:17:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000460","title":"Whole_Genome_sequencing_of_individuals_from_Carlantino__Italy","description":"This study includes whole-genome sequencing data (at 4x depth) of 100 individuals from an Italian genetic isolate population (Carlantino, abbreviated CARL) of the Italian Network of Genetic Isolates (INGI). The INGI-CARL_SEQ project aims to combine available extensive genetic and phenotypic data to the latest high-throughput genome sequencing technology and ad hoc statistical analysis to identify new rare genetic variants underlying complex traits.","abstract":"This study includes whole-genome sequencing data (at 4x depth) of 100 individuals from an Italian genetic isolate population (Carlantino, abbreviated CARL) of the Italian Network of Genetic Isolates (INGI). The INGI-CARL_SEQ project aims to combine available extensive genetic and phenotypic data to the latest high-throughput genome sequencing technology and ad hoc statistical analysis to identify new rare genetic variants underlying complex traits.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-03-20T14:50:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000462","title":"Autozygosity_pilot_Born_in_Bradford","description":"The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry.  In the UK there are large populations with very high first cousin marriage rates of 20-50%.  Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations.  This pilot study based on existing cohort samples from the Born In Bradford study will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed.  The data deposited in the EGA consist of  low coverage whole exome sequencing on these samples.","abstract":"The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry.  In the UK there are large populations with very high first cousin marriage rates of 20-50%.  Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations.  This pilot study based on existing cohort samples from the Born In Bradford study will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed.  The data deposited in the EGA consist of  low coverage whole exome sequencing on these samples.","study_type":"Other","pubmed_ids":[26940866],"external_links":null,"is_released":true,"released_date":"2013-03-21T08:18:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000464","title":"Validation_of_SNVs_found_by_Exome_seq_in_S2_SF1___SF5_and__SF9_hiPSCs","description":"PCR products were obtained from each target loci using genomic DNA from human iPS cells. Subsequently, PCR products are pooled and subjected to Illumina library preparation.  The library will be sequenced either by HiSeq or MiSeq. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Human induced pluripotent stem (iPS) cells could offer the prospect of autologous cell-replacement therapy to treat patients with genetic diseases. It is now known that human iPS cells carry tens of point mutations compared to the donor genome and often carry copy number changes. For safe use of human iPS cells in clinic, understanding the integrity of the iPS cell genome is important. We have analysed how these point mutations were introduced into the iPS cells genome by whole genome sequencing of iPS cells derived from monoclonal primary somatic cells. We found that 500-1000 SNVs were introduced during primary cell culture and reprogramming. We would like to perform deep sequencing of these SNVs in parental population to analyse the rate of culture-induced mutations","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-03-25T14:18:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000466","title":"FFPE_CPA_Accreditation_Study","description":"FFPE CPA accreditation of genome-scale sequencing in routinely collected formalin-fixed paraffin-embedded (FFPE) cancer specimens versus matched fresh-frozen samples using targeted pulldown capture prior to Illumina sequencing.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale. Being able to follow up studies in a larger cohort from FFPE samples would greatly increase the capacity of these studies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-03-26T12:52:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000468","title":"Harnessing_transposons_for_drug_resistance_gene_discovery_in_cancer","description":"This study involves a forward genetic screen to identify common insertion sites in drug resistant clones. We will be utilising piggybac transposon systems in order to generate multiple drug resistant clones in a range of human cancer cell lines.","abstract":"In the last decade we have begun to move towards the use of targeted therapeutics in the clinic, often resulting in dramatic response rates in cancer patients. However, clinical experience has demonstrated time and time again that such responses are invariably followed by the development of drug resistance. Identification of the underlying mechanisms may enable us to reverse such resistance. Traditional methods of modelling this resistance in vitro can lead to a plethora of potential resistance mechanisms that can be difficult to decipher.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-03-26T13:53:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000470","title":"CMF_RNA_sequencing","description":"RNA sequencing will be undertaken to reconstruct rearrangements at level of transcription to determine pathogenomic genomic events in chondromyxoid fibroma","abstract":"Chondromyxoid fibroma is a benign tumour of bone with unknown underlying pathogenesis. To determine pathognomic genomic events in chondromyxoid fibroma RNA sequencing will be undertaken to reconstruct rearrangements at level of transcription","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-03-26T16:13:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000472","title":"Whole genome sequencing, SNP array and  RNA-seq of uveal melanomas","description":"We conducted whole genome sequencing and DNA SNP array of 12 uveal melanoma genomes and their matched DNA from blood. We also conducted RNA-seq of the 12 tumour samples.","abstract":"We conducted whole genome sequencing and DNA SNP array of 12 uveal melanoma genomes and their matched DNA from blood. We also conducted RNA-seq of the 12 tumour samples.","study_type":"Other","pubmed_ids":[23861464],"external_links":null,"is_released":true,"released_date":"2013-03-27T11:52:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000474","title":"Whole genome sequencing and whole exome sequencing of mucosal melanoma","description":"We conducted whole genome sequencing of 5 mucosal melanomas and their matched DNA from blood. We conducted whole exome sequencing of a further 5 mucosal melanomas and their matched DNA from blood.","abstract":"We conducted whole genome sequencing of 5 mucosal melanomas and their matched DNA from blood. We conducted whole exome sequencing of a further 5 mucosal melanomas and their matched DNA from blood.","study_type":"Other","pubmed_ids":[23620124],"external_links":null,"is_released":true,"released_date":"2013-03-27T12:23:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000476","title":"Negligible impact on missing heritability of autoimmune-locus rare coding-region variants","description":"Genome wide association studies (GWAS) have identified common variants of modest effect size at hundreds of loci for common autoimmune diseases - however a substantial fraction of heritability remains unexplained, and to which rare variants may contribute.  To discover rare variants and test them for association with a phenotype, the majority of studies re-sequence a small initial sample size and then genotype the discovered variants in a larger sample set. This approach will fail to analyse a large fraction of the rare variants present in the entire sample set. Here we perform simultaneous amplicon sequencing-based variant discovery and genotyping for coding exons of 25 GWAS risk genes in 41,911 white-European origin UK subjects comprising 24,892 subjects with six autoimmune disease phenotypes and 17,019 controls, and show that rare coding-region variants at known loci play a negligible role in common autoimmune disease susceptibility. These results do not support the rare variant - synthetic genome-wide association hypothesis. Many known autoimmune disease risk loci contain multiple independent common and low frequency variant association signals, and so genes in these loci are a priori stronger candidates to harbor rare coding-region variants than other genes. Our data suggest that the missing heritability for common autoimmune diseases may not lie in the rare coding-region variant portion of the allelic spectrum, but perhaps as others have proposed in very many common variant signals of weak effect.","abstract":"Genome wide association studies (GWAS) have identified common variants of modest effect size at hundreds of loci for common autoimmune diseases - however a substantial fraction of heritability remains unexplained, and to which rare variants may contribute.  To discover rare variants and test them for association with a phenotype, the majority of studies re-sequence a small initial sample size and then genotype the discovered variants in a larger sample set. This approach will fail to analyse a large fraction of the rare variants present in the entire sample set. Here we perform simultaneous amplicon sequencing-based variant discovery and genotyping for coding exons of 25 GWAS risk genes in 41,911 white-European origin UK subjects comprising 24,892 subjects with six autoimmune disease phenotypes and 17,019 controls, and show that rare coding-region variants at known loci play a negligible role in common autoimmune disease susceptibility. These results do not support the rare variant - synthetic genome-wide association hypothesis. Many known autoimmune disease risk loci contain multiple independent common and low frequency variant association signals, and so genes in these loci are a priori stronger candidates to harbor rare coding-region variants than other genes. Our data suggest that the missing heritability for common autoimmune diseases may not lie in the rare coding-region variant portion of the allelic spectrum, but perhaps as others have proposed in very many common variant signals of weak effect.","study_type":"Resequencing","pubmed_ids":[23698362],"external_links":null,"is_released":true,"released_date":"2013-04-04T16:53:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000478","title":"Genetic_factors_underlying_premature_MI_in_Greek_families_without_vessel_disease","description":"The study will analyse by exome sequencing 8 Greek family members with an excess of potentially damaging mutations relating to premature MI and no vessel disease, to identify genetic factors underlying this condition. This is a follow on from project GPMI-NVD","abstract":"We have recruited additional family members from four of the most genetically interesting Greekfamilies with premature MI. Exome analysis of the probands of these families has excluded mutationsin the known familial hypercholesterolemia genes but we find an excess of potentially damagingnon synonymous changes which we have been unable to filter out. We propose to exome sequencetwo additional members per family - one unaffected parent and one affected sibling(cardiovascular disease).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-04-05T12:00:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000480","title":"Egypt_Genome_Project___low_coverage_whole_genome_sequencing","description":"All humans outside Africa are descendants of the same single exit, usually dated at 50-70 thousand years ago. However, the route taken out of Africa is still debated. The two main candidates are a northern route via Egypt and the Levant, or a southern route via Ethiopia and the Arabian Peninsula. We are generating genetic data to evaluate these two possibilities. In this study we propose to generate low-coverage sequencing data for 100 Egyptian samples.","abstract":"All humans outside Africa are descendants of the same single exit, usually dated at 50-70 thousand years ago. However, the route taken out of Africa is still debated. The two main candidates are a northern route via Egypt and the Levant, or a southern route via Ethiopia and the Arabian Peninsula. We are generating genetic data to evaluate these two possibilities. In this study we propose to generate low-coverage sequencing data for 100 Egyptian samples.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-04-09T14:37:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000482","title":"Egypt_Genome_Project___high_coverage_whole_genome_sequencing","description":"All humans outside Africa are descendants of the same single exit, usually dated at 50-70 thousand years ago. However, the route taken out of Africa is still debated. The two main candidates are a northern route via Egypt and the Levant, or a southern route via Ethiopia and the Arabian Peninsula. We are generating genetic data to evaluate these two possibilities. In this study we propose to generate high-coverage sequencing data for 3 Egyptian samples.","abstract":"All humans outside Africa are descendants of the same single exit, usually dated at 50-70 thousand years ago. However, the route taken out of Africa is still debated. The two main candidates are a northern route via Egypt and the Levant, or a southern route via Ethiopia and the Arabian Peninsula. We are generating genetic data to evaluate these two possibilities. In this study we propose to generate high-coverage sequencing data for 3 Egyptian samples.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-04-09T14:53:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000484","title":"Whole genome and transcriptome analysis of a sporadic and recurring parathyroid carcinoma","description":"Parathyroid carcinoma is an extremely rare endocrine malignancy with an estimated incidence of less than 1 per million population. Excessive secretion of parathyroid hormone, extremely high serum calcium level and the deleterious effects of hypercalcemia are the clinical manifestations of the disease. Up to 60% of patients develop multiple disease recurrences and although long-term survival is possible with palliative surgery, permanent remission is rarely achieved. Molecular drivers of sporadic parathyroid carcinoma have remained largely unknown. Previous studies, mostly based on familial cases of the disease, suggested a potential role for the tumor suppressor MEN1 and proto-oncogene RET in benign parathyroid tumorigenesis while the tumor suppressor HRPT2 and proto-oncogene CCND1 may also act as drivers in parathyroid cancer. Here, we report the complete genomic analysis of a sporadic and recurring parathyroid carcinoma. Mutational landscapes of the primary and recurrent tumor specimens were analyzed using high throughput sequencing technologies. Such molecular profiling allowed for identification of somatic mutations never previously identified in this malignancy. These included single nucleotide point mutations in well characterized cancer genes such as mTOR, MLL2, CDKN2C and PIK3CA. Comparison of acquired mutations in patient-matched primary and recurrent tumors revealed loss of PIK3CA activating mutation during the evolution of the tumor from the primary to the recurrence. Structural variations leading to gene fusions and regions of copy loss and gain were identified at a single-base resolution. Loss of short arm of chromosome 1 along with somatic mis-sense and truncating mutations in CDKN2C and THRAP3, respectively, provide new evidence for the potential role of these genes as tumor suppressors in parathyroid cancer. The key somatic mutations indentified in this study can serve as novel diagnostic markers as well as therapeutic targets.","abstract":"Parathyroid carcinoma is an extremely rare endocrine malignancy with an estimated incidence of less than 1 per million population. Excessive secretion of parathyroid hormone, extremely high serum calcium level and the deleterious effects of hypercalcemia are the clinical manifestations of the disease. Up to 60% of patients develop multiple disease recurrences and although long-term survival is possible with palliative surgery, permanent remission is rarely achieved. Molecular drivers of sporadic parathyroid carcinoma have remained largely unknown. Previous studies, mostly based on familial cases of the disease, suggested a potential role for the tumor suppressor MEN1 and proto-oncogene RET in benign parathyroid tumorigenesis while the tumor suppressor HRPT2 and proto-oncogene CCND1 may also act as drivers in parathyroid cancer. Here, we report the complete genomic analysis of a sporadic and recurring parathyroid carcinoma. Mutational landscapes of the primary and recurrent tumor specimens were analyzed using high throughput sequencing technologies. Such molecular profiling allowed for identification of somatic mutations never previously identified in this malignancy. These included single nucleotide point mutations in well characterized cancer genes such as mTOR, MLL2, CDKN2C and PIK3CA. Comparison of acquired mutations in patient-matched primary and recurrent tumors revealed loss of PIK3CA activating mutation during the evolution of the tumor from the primary to the recurrence. Structural variations leading to gene fusions and regions of copy loss and gain were identified at a single-base resolution. Loss of short arm of chromosome 1 along with somatic mis-sense and truncating mutations in CDKN2C and THRAP3, respectively, provide new evidence for the potential role of these genes as tumor suppressors in parathyroid cancer. The key somatic mutations indentified in this study can serve as novel diagnostic markers as well as therapeutic targets.","study_type":"Whole Genome Sequencing","pubmed_ids":[23616356],"external_links":null,"is_released":true,"released_date":"2013-04-09T20:08:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000486","title":"Whole genome sequencing of acral melanomas","description":"We conducted whole genome sequencing of 5 acral melanoma genomes and their matched DNA from blood.","abstract":"We conducted whole genome sequencing of 5 acral melanoma genomes and their matched DNA from blood.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-04-12T10:40:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000488","title":"Sequencing_probands_and_families_with_severe_insulin_resistance_syndromes","description":"This is an ongoing project and continuation to all the sequencing we have been doing over the last few years.  We have some additional families and probands with syndromes of insulin resistance not previously sequenced within uk10k or other core funded projects.  We  would like to complete the sequencing in all of the good quality families and probands we have, this would require another ~50 samples to be WES sequenced.  This cohort has already proven to be a rich source of interesting findings with papers in Science and Nature genetics.","abstract":"Over the last 10 years or so, candidate gene re-sequencing in individuals with severe insulin resistance has led to the discovery of genes that when mutated are causative of those particular phenotypes.  With the development of new sequencing technology, sequencing all exons in the genome has become possible.  This has enabled us, in collaboration with Steve O?Rahilly, Rob Semple and David Savage, to investigate disorders of insulin action in patients for whom the underlying causative mutation(s) remain unknown.  This study will complete the sequencing of all the good quality Severe Insulin Resistance families and probands we have.  This cohort has already proven to be a rich source of interesting findings with papers in Science and Nature Genetics.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-04-17T08:52:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000490","title":"Sequencing_component_for_the_whole_genome_methylation_analysis_in_PBMCs_and_cell_subsets__pilot_study_","description":"DNA methylation has been shown to play a major role in determining cellular phenotype by regulating gene expression. Moreover, dysregulation of differentially methylated genes has been implicated in disease pathogenesis of various conditions including cancer development as well as autoimmune diseases such as systemic Lupus erythematosus and rheumatoid arthritis. Evidence is rapidly accumulating for a role of DNA methylation in regulating immune responses in health and disease. However, the exact mechanisms remain unknown. The overall aim of the project is to investigate the role of epigenetic mechanisms in regulating immunity and their impact on autoimmune disease pathogenesis.The aim of this pilot study is to perform whole genome methylation analysis in peripheral blood mononuclear cells (PBMCs) and cell subsets (CD4, CD8, CD14, CD19, CD16 and whole PBMCs) obtained from 6 healthy volunteers. Whole genome methylation analysis will be performed using two methodological approaches, the Infinium Methylation Bead Array K450 (Illumina) and MeDIP-seq. mRNA expression arrays will also be performed in order to correlate DNA methylation with gene expression as well as genotyping on the Illumina OmniExpress chip","abstract":"DNA methylation has been shown to play a major role in determining cellular phenotype by regulating gene expression. Moreover, dysregulation of differentially methylated genes has been implicated in disease pathogenesis of various conditions including cancer development as well as autoimmune diseases such as systemic Lupus erythematosus and rheumatoid arthritis. Evidence is rapidly accumulating for a role of DNA methylation in regulating immune responses in health and disease. However, the exact mechanisms remain unknown. The overall aim of the project is to investigate the role of epigenetic mechanisms in regulating immunity and their impact on autoimmune disease pathogenesis.The aim of this pilot study is to perform whole genome methylation analysis in peripheral blood mononuclear cells (PBMCs) and cell subsets (CD4, CD8, CD14, CD19, CD16 and whole PBMCs) obtained from 6 healthy volunteers. Whole genome methylation analysis will be performed using two methodological approaches, the Infinium Methylation Bead Array K450 (Illumina) and MeDIP-seq. mRNA expression arrays will also be performed in order to correlate DNA methylation with gene expression as well as genotyping on the Illumina OmniExpress chip","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-04-22T11:47:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000492","title":"Assessment_of_genetic_and_epigenetic_variation_in_human_IPS_cells","description":"In order to progress human induced pluripotent stem cells (hiPSCs) towards the clinic, several outstanding questions must be addressed. It is possible to reprogram different somatic cell types into hiPSCs  but it is unlcear whether some cell types carry through fewer mutations through reprogramming (either due to mutations present in the primary cells, or mutations accumulated during reprogramming). Through in depth analysis of hiPSCs generated from different somatic cells, it will be possible to assess the variation in genetic stability of different cell types.","abstract":"In order to progress human induced pluripotent stem cells (hiPSCs) towards the clinic, several outstanding questions must be addressed. It is possible to reprogram different somatic cell types into hiPSCs  but it is unlcear whether some cell types carry through fewer mutations through reprogramming (either due to mutations present in the primary cells, or mutations accumulated during reprogramming). Through in depth analysis of hiPSCs generated from different somatic cells, it will be possible to assess the variation in genetic stability of different cell types.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-04-23T07:59:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000495","title":"RNA Editing in breast cancer","description":"High-throughput sequencing screens suggest that RNA editing, which consists in the substitution of adenosine with inosine by the RNA-specific adenosine deaminase (ADAR) enzyme, occurs at several thousand positions across the human genome. Recent evidences have shown that RNA-editing could promote proliferation and carcinogenesis; however, the general principles of ADAR activity on the transcriptome and how ADAR is controlled in cancers remain to be established. The main aim of this project was to investigate the phenomenon of RNA editing in breast and other cancers. The frequency of A-to-I editing was evaluated in 58 breast cancers equally distributed among the different molecular subtypes and 10 normal breast tissues. The analysis was focused on defining: the relationship between the global amount of editing and ADAR expression; the ability to predict the level of editability of specific sites; the distribution of editing in normal and tumour samples and among different breast cancer subtypes; and the clinical, pathological and genomic factors affecting editing.","abstract":"High-throughput sequencing screens suggest that RNA editing, which consists in the substitution of adenosine with inosine by the RNA-specific adenosine deaminase (ADAR) enzyme, occurs at several thousand positions across the human genome. Recent evidences have shown that RNA-editing could promote proliferation and carcinogenesis; however, the general principles of ADAR activity on the transcriptome and how ADAR is controlled in cancers remain to be established. The main aim of this project was to investigate the phenomenon of RNA editing in breast and other cancers. The frequency of A-to-I editing was evaluated in 58 breast cancers equally distributed among the different molecular subtypes and 10 normal breast tissues. The analysis was focused on defining: the relationship between the global amount of editing and ADAR expression; the ability to predict the level of editability of specific sites; the distribution of editing in normal and tumour samples and among different breast cancer subtypes; and the clinical, pathological and genomic factors affecting editing.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-04-23T19:35:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000498","title":"Autism_Genetics_in_the_Norwegian_Mother_and_Child_Cohort","description":"These samples are family trios (mother-father-offspring) where the child has been diagnosed with an autism spectrum disorder (ASD). In some cases where paternal DNA is not available, mother-child dyads were included. Children with ASD are identified among members of the Norwegian Mother and Child Cohort (MoBa). The autism component of MoBa is called the Autism Birth Cohort (ABC) study. All samples have been exome sequenced using Agilent indexed squence capture and Illumina 75bp PE HiSeq sequencing.","abstract":"These samples are family trios (mother-father-offspring) where the child has been diagnosed with an autism spectrum disorder (ASD). In some cases where paternal DNA is not available, mother-child dyads were included. Children with ASD are identified among members of the Norwegian Mother and Child Cohort (MoBa). The autism component of MoBa is called the Autism Birth Cohort (ABC) study. All samples have been exome sequenced using Agilent indexed squence capture and Illumina 75bp PE HiSeq sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000500","title":"Sequencing and analysis of three plant growth promoting rhizobacteria isolated from the rhizosphere of plantation crops coconut, cocoa and arecanut","description":"Coconut, cocoa and arecanut are commercial plantation crops that play a vital role in the Indian economy. We sequenced three plant growth promoting rhizobacteria from coconut (CPCRI-1), cocoa (CPCRI-2) and arecanut (CPCRI-3) respectively.  The draft genome sequences for CPCRI-1 [4.7 Mb],  CPCRI-2 [5.9 Mb] and for CPCRI-3 [5.1 Mb] encode 4056, 4637 and 4286 protein-coding genes, respectively.  CPCRI-1 and CPCRI-3 belong to Enterobacteriaceae family and CPCRI-2 groups with Pseudomonadacea family.  Genomes of all three bacteria contain genes for central carbohydrate metabolism, indole acetic acid production and quorum sensing indicating the presence of plant growth promoting traits. Functional annotation comparison identified several differentially enriched groups. For example, CPCRI-2 genome contains higher percentage of transcription initiation and regulation and siderophore pyoverdin genes compared to the CPCRI-1 and CPCRI-3.  CPCRI-2 genome contains several genes involved in the degradation of various aromatic compounds such as benzoate, tetrachloroethane, bisphenolA etc. CPCRI-1 genome contains a large number of genes associated with flagella and pili biosynthesis as compared to CPCRI-2 and CPCRI-3 genomes. Genome sequences of these bacteria will enhance our understanding of the interactions between these rhizobacteria and their respective crops. This will help in designing sustainable agriculture strategies by using rhizobacteria as growth promoting agents.","abstract":"Coconut, cocoa and arecanut are commercial plantation crops that play a vital role in the Indian economy. We sequenced three plant growth promoting rhizobacteria from coconut (CPCRI-1), cocoa (CPCRI-2) and arecanut (CPCRI-3) respectively.  The draft genome sequences for CPCRI-1 [4.7 Mb],  CPCRI-2 [5.9 Mb] and for CPCRI-3 [5.1 Mb] encode 4056, 4637 and 4286 protein-coding genes, respectively.  CPCRI-1 and CPCRI-3 belong to Enterobacteriaceae family and CPCRI-2 groups with Pseudomonadacea family.  Genomes of all three bacteria contain genes for central carbohydrate metabolism, indole acetic acid production and quorum sensing indicating the presence of plant growth promoting traits. Functional annotation comparison identified several differentially enriched groups. For example, CPCRI-2 genome contains higher percentage of transcription initiation and regulation and siderophore pyoverdin genes compared to the CPCRI-1 and CPCRI-3.  CPCRI-2 genome contains several genes involved in the degradation of various aromatic compounds such as benzoate, tetrachloroethane, bisphenolA etc. CPCRI-1 genome contains a large number of genes associated with flagella and pili biosynthesis as compared to CPCRI-2 and CPCRI-3 genomes. Genome sequences of these bacteria will enhance our understanding of the interactions between these rhizobacteria and their respective crops. This will help in designing sustainable agriculture strategies by using rhizobacteria as growth promoting agents.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000501","title":"Bone_Cancer___Rare_Types_Whole_Genome","description":"We propose to definitively characterise the somatic genetics of a selection of rare bone cancers through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-05-01T12:45:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000503","title":"Bridging_the_Evolution_and_Epidemiology_of_HIV_in_Europe","description":"Bridging the Evolution and Epidemiology of HIV in Europe - BEEHIVEThe aim of the BEEHIVE project is to generate novel insight into HIV-1 biology, evolution and epidemiology, leveraging next-generation high-throughput sequencing and bioinformatics to generate and analyse whole genomes of viruses from European HIV-1 infected patients. These patients have known dates of infection spread over the last 25 years, good clinical follow up, and a wide range of clinical prognostic indicators and outcomes. The primary objective is to discover the viral genetic determinants of severity of HIV-1 infection and set-point viral load - the viral load that stabilises after a brief peak during early infection. We will undertake the first genome wide association study for an RNA virus to discover HIV-1 mutations that increase or decrease the severity of infection. The secondary objective is to use viral genetic sequences allied to mathematical epidemic models to better understand the resurgent European HIV-1 epidemic. Tertiary objectives involve understanding the relationship between the genetic diversity within viral samples, indicative of on-going evolution or dual infections, to clinical outcomes.","abstract":"Bridging the Evolution and Epidemiology of HIV in Europe - BEEHIVEThis study generates whole genome sequences of Human Immunodeficiency Virus 1 (HIV-1) from European patients with known dates infection over the last 25 years. Plasma samples were collected, viral RNA was extracted and the HIV-1 genome was amplified using our universal “pan-HIV-1 primer set (Gall et al. 2012, J. Clin. Microbiol. 50:12, 3838-44). Products were pooled in equimolar amounts and sequenced using the Illumina MiSeq technology. The data set generated in this study enables analysis of the viral genetic determinants of severity of HIV-1 infection, the epidemiology of the resurgent European HIV-1 epidemic and the viral genetic diversity within patients.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000505","title":"Whole genome sequencing of chondrosarcoma","description":"Massive parallel sequencing of 10 chondrosarcoma genomes  was conducted to identify somatic mutations, structural alterations including fusion genes and mutation signatures that may help to comprehensively characterize the molecular features.","abstract":"Massive parallel sequencing of 10 chondrosarcoma genomes  was conducted to identify somatic mutations, structural alterations including fusion genes and mutation signatures that may help to comprehensively characterize the molecular features.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-05-08T12:49:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000506","title":"Comprehensive analysis of atypical teratoid rhabdoid tumour (ATRT) using genomic, epigenomic and transcriptomic techniques.","description":"ATRTs (Atypical teratoid rhabdoid tumours) represent one of the most aggressive pediatric brain cancers, but intriguingly exhibit few other recurrently mutated loci except for  SMARCB1/hSNF5.  We integrated whole genome (n=15), exome, copy number, gene expression and methylation analyses to comprehensively interrogate 64 ATRTs and observed that structural events were relatively frequent in the ATRT genome (~3 tumour).  In addition to SMARCB1, which was targeted by structural events in a majority (49/64) of tumours, recurrent structural alterations targeting the LRP1B, CDH13, BCR and MKL1 loci were observed. We observed novel translocation events, including 2 targeting SMARCB1 which were detected only by NGS analyses. Significantly, integration of gene expression and methylation profiles with genomic analyses revealed ATRT comprise two sub-groups with distinct clinical and genetic features.  Group 1 tumours were characterized by supra-tentorial brain location, focal intragenic alterations of SMARCB1 and a pro-neural gene expression signature with evidence of NOTCH pathway activation.  While Group 2 ATRTs were characterized by infra-tentorial brain location, broad SMARCB1 alterations and an activation of the BMP signalling pathway. Our findings highlight epigenetic mechanisms as important determinants of ATRT tumour phenotypes, and demonstrate for the first time that ATRTs arising in different anatomical compartments comprise distinct molecular and therapeutic sub-groups.","abstract":"ATRTs (Atypical teratoid rhabdoid tumours) represent one of the most aggressive pediatric brain cancers, but intriguingly exhibit few other recurrently mutated loci except for  SMARCB1/hSNF5.  We integrated whole genome (n=15), exome, copy number, gene expression and methylation analyses to comprehensively interrogate 64 ATRTs and observed that structural events were relatively frequent in the ATRT genome (~3 tumour).  In addition to SMARCB1, which was targeted by structural events in a majority (49/64) of tumours, recurrent structural alterations targeting the LRP1B, CDH13, BCR and MKL1 loci were observed. We observed novel translocation events, including 2 targeting SMARCB1 which were detected only by NGS analyses. Significantly, integration of gene expression and methylation profiles with genomic analyses revealed ATRT comprise two sub-groups with distinct clinical and genetic features.  Group 1 tumours were characterized by supra-tentorial brain location, focal intragenic alterations of SMARCB1 and a pro-neural gene expression signature with evidence of NOTCH pathway activation.  While Group 2 ATRTs were characterized by infra-tentorial brain location, broad SMARCB1 alterations and an activation of the BMP signalling pathway. Our findings highlight epigenetic mechanisms as important determinants of ATRT tumour phenotypes, and demonstrate for the first time that ATRTs arising in different anatomical compartments comprise distinct molecular and therapeutic sub-groups.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-05-08T14:53:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000507","title":"Genomic_stability_of_a_feeder_independent_human_iPS_cell_line","description":"Human iPS cells were kindly provided by collaborators (F.Rouhani and  L.Vallier). These were previously derived from fibroblasts. Cells were grown on MEF feeders to passage 13. Genomic DNA was extracted  using standard protocols (Qiagen). DNA will be subject to library preparation and sequencing on the Illumina HiSeq or MiSeq. Sequence reads will be aligned to the human genome reference. Genomic variants will be compared to data previously obtained from the same cell line at lower passage, and assesd for a) de novo mutations and b) mutations in BAF complex genes .This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Genomic engineering of human iPS cells provide an eccessible model for the study of human disease. We are currently studying a group of genes involved in intellectual disability, and propose to create molecular models of disease in human iPS cells. Prior to initiating any genetic manipulations on this cell line, we would like to recharacterise its genome and determine whether the rate of mutation and specific genes mutated may compromise the downstream analysis of the function of the genes of interest.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000509","title":"an integrated molecular study of clear cell renal cell carcinoma (ccRCC) including whole-genome/exome and RNA sequencing as well as array-based gene expression/copy-number/methylation analyses","description":"an integrated molecular study of clear cell renal cell carcinoma (ccRCC) including whole-genome/exome and RNA sequencing as well as array-based gene expression/copy-number/methylation analyses","abstract":"an integrated molecular study of clear cell renal cell carcinoma (ccRCC) including whole-genome/exome and RNA sequencing as well as array-based gene expression/copy-number/methylation analyses","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-05-13T07:19:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000510","title":"Landscape of somatic mutations and clonal evolution in mantle cell lymphoma","description":"Mantle cell lymphoma (MCL) is an aggressive tumor, but a subset of patients may follow an indolent clinical course. To understand the mechanisms underlying this biological heterogeneity, we performed whole-genome and/or whole-exome sequencing on 29 MCL cases and their respective matched normal DNA, as well as 6 MCL cell lines. Recurrently mutated genes were investigated by targeted sequencing in an independent cohort of 172 MCL patients. We identified 25 significantly mutated genes, including known drivers such as ataxia-telangectasia mutated (ATM), cyclin D1 (CCND1), and the tumor suppressor TP53; mutated genes encoding the anti-apoptotic protein BIRC3 and Toll-like receptor 2 (TLR2); and the chromatin modifiers WHSC1, MLL2, and MEF2B. We also found NOTCH2 mutations as an alternative phenomenon to NOTCH1 mutations in aggressive tumors with a dismal prognosis. Analysis of two simultaneous or subsequent MCL samples by whole-genome/whole-exome (n = 8) or targeted (n = 19) sequencing revealed subclonal heterogeneity at diagnosis in samples from different topographic sites and modulation of the initial mutational profile at the progression of the disease. Some mutations were predominantly clonal or subclonal, indicating an early or late event in tumor evolution, respectively. Our study identifies molecular mechanisms contributing to MCL pathogenesis and offers potential targets for therapeutic intervention.","abstract":"Mantle cell lymphoma (MCL) is an aggressive tumor, but a subset of patients may follow an indolent clinical course. To understand the mechanisms underlying this biological heterogeneity, we performed whole-genome and/or whole-exome sequencing on 29 MCL cases and their respective matched normal DNA, as well as 6 MCL cell lines. Recurrently mutated genes were investigated by targeted sequencing in an independent cohort of 172 MCL patients. We identified 25 significantly mutated genes, including known drivers such as ataxia-telangectasia mutated (ATM), cyclin D1 (CCND1), and the tumor suppressor TP53; mutated genes encoding the anti-apoptotic protein BIRC3 and Toll-like receptor 2 (TLR2); and the chromatin modifiers WHSC1, MLL2, and MEF2B. We also found NOTCH2 mutations as an alternative phenomenon to NOTCH1 mutations in aggressive tumors with a dismal prognosis. Analysis of two simultaneous or subsequent MCL samples by whole-genome/whole-exome (n = 8) or targeted (n = 19) sequencing revealed subclonal heterogeneity at diagnosis in samples from different topographic sites and modulation of the initial mutational profile at the progression of the disease. Some mutations were predominantly clonal or subclonal, indicating an early or late event in tumor evolution, respectively. Our study identifies molecular mechanisms contributing to MCL pathogenesis and offers potential targets for therapeutic intervention.","study_type":"Whole Genome Sequencing","pubmed_ids":[24145436],"external_links":null,"is_released":true,"released_date":"2013-05-13T11:45:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000511","title":"Autozygosity_pilot___Pakistani_from_Birmingham","description":"The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry.  In the UK there are large populations with very high first cousin marriage rates of 50-80%.  Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations.  This pilot study based on existing British-Pakistani cohort samples from Birmingham will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed.  The data deposited in the EGA consist of  low coverage whole exome sequencing on these samples.","abstract":"The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry.  In the UK there are large populations with very high first cousin marriage rates of 50-80%.  Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations.  This pilot study based on existing British-Pakistani cohort samples from Birmingham will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed.  The data deposited in the EGA consist of  low coverage whole exome sequencing on these samples.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-05-15T08:10:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000513","title":"COLORS_in_IBD__Whole_exome_sequencing_of_early_onset_IBD_patients","description":"Exome sequence analysis of individuals with severe early onset inflammatory bowel disease, and their families. Individuals are ascertained through the COLORS in IBD study, which includes centres throughout UK and Europe.","abstract":"It has been shown that severe early onset inflammatory bowel disease (SEOIBD) can be caused by high penetrance exonic mutations. Only a fraction of SEOIBD cases are explained by mutations in known SEOIBD genes. Following screening for mutations in known  SEOIBD genes, we will whole exome sequence unexplained SEOIBD cases in an effort to identify causal mutations underpinning susceptibility to disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-05-20T10:40:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000514","title":"ERG ALTERATIONS DEFINE A NOVEL SUBTYPE OF ACUTE LYMPHOBLASTIC LEUKEMIA","description":"Structural chromosomal alterations are a hallmark of acute lymphoblastic leukemia (ALL) yet many patients lack an identifiable abnormality on conventional cytogenetic analysis. Here, using integrated analysis of genome-wide DNA copy number and gene expression data of 1764 childhood and adult ALL cases, including whole-genome, exome and mRNA-sequencing of 72 cases, we report a novel subtype of B-progenitor ALL (B-ALL) representing 4-13% of B-ALL cases characterized by a distinct gene expression profile, and focal deletions of ERG (ETS related gene) in 56% of cases. These cases are characterized by expression of a ERG transcript that utilizes a novel exon in intron 6 of ERG spliced to the canonical reading frame of ERG exons 7-10, encoding a 27 kDa C-terminal ERG protein that retains the ETS and transactivating domains but lacks the N-terminal pointed and regulatory domains. This protein is a competitive inhibitor of wild-type ERG and is leukemogenic in vivo. ERG-altered ALL cases have a favourable outcome despite the presence of alterations associated with poor prognosis in non-ERG ALL, such as deletions of IKZF1. These findings identify a new subtype of leukemia characterized by a novel mechanism of ETS transcription factor dysregulation in cancer.","abstract":"Structural chromosomal alterations are a hallmark of acute lymphoblastic leukemia (ALL) yet many patients lack an identifiable abnormality on conventional cytogenetic analysis. Here, using integrated analysis of genome-wide DNA copy number and gene expression data of 1764 childhood and adult ALL cases, including whole-genome, exome and mRNA-sequencing of 72 cases, we report a novel subtype of B-progenitor ALL (B-ALL) representing 4-13% of B-ALL cases characterized by a distinct gene expression profile, and focal deletions of ERG (ETS related gene) in 56% of cases. These cases are characterized by expression of a ERG transcript that utilizes a novel exon in intron 6 of ERG spliced to the canonical reading frame of ERG exons 7-10, encoding a 27 kDa C-terminal ERG protein that retains the ETS and transactivating domains but lacks the N-terminal pointed and regulatory domains. This protein is a competitive inhibitor of wild-type ERG and is leukemogenic in vivo. ERG-altered ALL cases have a favourable outcome despite the presence of alterations associated with poor prognosis in non-ERG ALL, such as deletions of IKZF1. These findings identify a new subtype of leukemia characterized by a novel mechanism of ETS transcription factor dysregulation in cancer.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-05-20T17:19:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000515","title":"Use_of_Deep_Sequencing_to_Dectect_Clonal_Mutations_In_Sun_Exposed_Skin_Epidermis","description":"This study aims to define the landscape of somatic mutations in sun exposed human skin by deep sequencing, analyse their frequency and use the data to infer the effect of mutations on proliferating cell behaviour. The frequency of each mutation will reflect the size of the clone of cells in the tissue sample. By analyzing small samples, clones with as few as 100 cells will be detectable. Allele frequency distributions for each mutation will be used to infer cell fate using published methods (Klein et al. 2010). This study will shed unprecedented light on the early clonal events that lead to the emergence of cancer.","abstract":"This study aims to define the landscape of somatic mutations in sun exposed human skin by deep sequencing, analyse their frequency and use the data to infer the effect of mutations on proliferating cell behaviour. The frequency of each mutation will reflect the size of the clone of cells in the tissue sample. By analyzing small samples, clones with as few as 100 cells will be detectable. Allele frequency distributions for each mutation will be used to infer cell fate using published methods (Klein et al. 2010). This study will shed unprecedented light on the early clonal events that lead to the emergence of cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-05-22T14:14:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000516","title":"Structural_Rearragement_of_Segmental_UPD_Chromosome","description":"This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This study aims to interrogate the breakpoint signature(s) for a complex structural rearragnement involving a large duplication and proximal loss of heterozygosity event. Results from thist study will be combined with results from collaborators for the purpose of understanding the origin and mechanism of similar events in other samples.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000517","title":"Finnish_population_history__genes_and_language__FINNUG_","description":"Finnish population history, genes and language (MURSU)","abstract":"Finnish population history, genes and language (MURSU)","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000518","title":"Angiosarcoma_follow_up_2_validation_study","description":"A bespoke targeted pulldown experiment will be performed on patients with Angiosarcoma. the resulting products will be sequenced to determine the prevalence of previously found mutations in these patients.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-05-24T10:43:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000519","title":"Bone_tumour_validation_study","description":"Targeted capture libraries will be sequenced to confirm the validity of mutations found in various bone cancer whole genome sequencing studies.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000520","title":"Cloning_of_the_breakpoint_of_a_novel_translocation_associated_with_T_acute_lymphoblastic_leukaemia","description":"Single case of T-ALL carrying t(4;6), a novel translocation.","abstract":"Paediatric T-ALL is a disease associated with a number of recurrent genomic rearrangements, many involving the TCR and SCL loci. Occasional cases, such as this one, carry unique translocations. Identifying the genetic loci involved, can give important insights into T-ALL pathogenesis","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-05-24T11:20:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000521","title":"Whole exome and whole genome sequencing of juvenile myelomonocytic leukemia (JMML)","description":"To obtain a complete registry of gene mutations in JMML, whole-exome sequencing was performed for paired tumor-normal DNA from 13 JMML cases, of which 2 cases were also analyzed by whole genome sequencing.","abstract":"To obtain a complete registry of gene mutations in JMML, whole-exome sequencing was performed for paired tumor-normal DNA from 13 JMML cases, of which 2 cases were also analyzed by whole genome sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-05-24T15:46:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000522","title":"An_exome_sequencing_study_of_the_HIV_elite_long_term_non_progressors_and_rapid_progressors__CASCADE_cohorts_","description":"Background: A rare subgroup of HIV infected individuals naturally controls infection withouttreatment. These ?elite controllers? constitute an important model for the natural control ofHIV infection. Indeed, the study of these individuals may provide insights into strategies forthe development of HIV vaccines. Although several HLA and chemokine alleles are knownto be over-represented in elite controllers, only a small portion of HIV phenotypic variation isexplained by known genetic variants. The elite controller phenotype is rare and distinct,representing the extreme of an infectious disease trait. As such, this phenotype may be partlyexplained by variation in host immune control, which may be characterized by differences inrare functional genetic variants. Genomic regions underlying elite control can be potentiallyidentified by comparing the presence or frequency of variants in this group to thatrepresenting the opposite extreme. In this context, ?rapid progressors? is a group defined byits rapid immunological and clinical disease progression.Aim: To extend an existing study, in order to identify DNA sequence variants involved in thecontrol of HIV infection with greater statistical resolution. Specifically, we aim to sequence upto 200 exomes from multiple cohort studies within the EuroCoord CASCADE collaboration (acollaboration of 25 HIV seroconversion cohort studies across Europe).","abstract":"A rare subgroup of HIV infected individuals naturally controls infection without treatment. The elite controller phenotype is rare and distinct, representing the extreme of an infectious disease trait and may be partly explained by variation in host immune control, which may be characterized by differences in rare functional genetic variants. Genomic regions underlying elite control can be potentially identified by comparing the presence or frequency of variants in this group to that representing the opposite extreme. In this context, ?rapid progressors? is a group defined by its rapid immunological and clinical disease progression. We aim to extend an existing study by sequencing  up to 200 exomes from multiple cohort studies within the EuroCoord CASCADE collaboration (a collaboration of 25 HIV seroconversion cohort studies across Europe).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-05-28T09:21:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000523","title":"ESGI_Identification_of_novel_genes_and_mechanisms_leading_to_Primary_Ciliary_Dyskinesia","description":"Approximately 80% of clinically clearly diagnosed patients suffering from primary ciliary dyskinesia (PCD) cannot be assigned to a specific gene defect. Despite extensive research on PCD and despite the increasing number of PCD genes and knowledge about their sites of action as e.g structural component or cytoplasmic pre-assembly factor, the biology of motile cilia and the pathomechanism leading to PCD is largely unknown. The aim of this study is to identify novel PCD related genes and processes relevant for motile cilia function.We will perform exome sequencing, aiming on the analysis of family trios.  In these families, the  diagnosis of PCD is secured, but the underlying gene defects has so far not been identified.","abstract":"Approximately 80% of clinically clearly diagnosed patients suffering from primary ciliary dyskinesia (PCD) cannot be assigned to a specific gene defect. Despite extensive research on PCD and despite the increasing number of PCD genes and knowledge about their sites of action as e.g structural component or cytoplasmic pre-assembly factor, the biology of motile cilia and the pathomechanism leading to PCD is largely unknown. The aim of this study is to identify novel PCD related genes and processes relevant for motile cilia function.We will perform exome sequencing, aiming on the analysis of family trios.  In these families, the  diagnosis of PCD is secured, but the underlying gene defects has so far not been identified.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-05-28T09:50:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000524","title":"Whole genome sequencing of tumour and normal paired biopsies from diffuse intrinsic pontine gliomas","description":"Diffuse intrinsic pontine glioma (DIPG) have a universally dismal prognosis (median 9-12 months), with neither chemotherapeutic nor targeted agents showing any substantial survival benefit in clinical trials in children with these tumours. DIPG are highly infiltrative malignant glial neoplasms of the ventral pons, which due to their location within the brain, make them unsuitable for surgical resection and consequently have a universally dismal clinical outcome. Recent high-throughput sequencing approaches have revealed a striking prevalence of K27M mutations in the genes encoding the histone variants H3.3 (H3F3A) or H3.1 (HIST1H3B) in the childhood brain tumour DIPG2. This K-to-M substitution confers a trans-dominant ablation of global H3K27 trimethylation, which likely profoundly alters gene expression through de-repression of polycomb repressive complex 2 (PRC2) target genes. Despite these advances in our understanding of the distinct biology of these tumours, approaches for specific novel therapeutic interventions are not clear, and little has been reported of the secondary mutations accompanying these changes. We carried out whole genome sequencing (EGAS00001000524) on a series of 20 pre-treatment biopsy samples of DIPG, for which the patients underwent a safe stereotactic procedure, and whole exome sequencing (EGAS00001000572) on a further six samples obtained at autopsy.","abstract":"Diffuse intrinsic pontine glioma (DIPG) have a universally dismal prognosis (median 9-12 months), with neither chemotherapeutic nor targeted agents showing any substantial survival benefit in clinical trials in children with these tumours. DIPG are highly infiltrative malignant glial neoplasms of the ventral pons, which due to their location within the brain, make them unsuitable for surgical resection and consequently have a universally dismal clinical outcome. Recent high-throughput sequencing approaches have revealed a striking prevalence of K27M mutations in the genes encoding the histone variants H3.3 (H3F3A) or H3.1 (HIST1H3B) in the childhood brain tumour DIPG2. This K-to-M substitution confers a trans-dominant ablation of global H3K27 trimethylation, which likely profoundly alters gene expression through de-repression of polycomb repressive complex 2 (PRC2) target genes. Despite these advances in our understanding of the distinct biology of these tumours, approaches for specific novel therapeutic interventions are not clear, and little has been reported of the secondary mutations accompanying these changes. We carried out whole genome sequencing (EGAS00001000524) on a series of 20 pre-treatment biopsy samples of DIPG, for which the patients underwent a safe stereotactic procedure, and whole exome sequencing (EGAS00001000572) on a further six samples obtained at autopsy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000525","title":"Analysis_of_somatic_mutations_in_normal_blood__AML_and_MDS_samples","description":"Targeted pulldown of genes known to be recurrently mutated in AML &amp; MDS from patient and normal samples using Agilent Sureselect and for some cases also using Illumina Truseq technology.","abstract":"Acute myeloid leukaemia (AML) is an aggressive and molecularly diverse disease with a poor overall survival of 20-25%. With an annual incidence of 2.9 per 100,000, AML is currently the commonest myeloid malignancy in Europe, yet the two main therapeutic options for this disease, anthracyclines and purine analogues, have remained unchanged for over 20 years. We recently described a targeted diagnostic approach for myeloid malignancies, which reliably identified mutations in 21 genes known to be recurrently mutated in AML. Also, a number of recent studies identified somatic mutations in the blood of some normal individuals. This study intends to validate a holistic diagnostic test for myeloid malignancies using a well-validated set of MDS and AML cases. Additionally, we will use this assay to search for somatic mutations in the blood of normal individuals and define the frequency and significance of this phenomenon.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-05-31T07:42:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000526","title":"Integrative sequencing reveals alterations in untreated and castration resistant prostate cancer","description":"We report the integrative sequencing of genomic, transcriptomic and DNA methylation changes in 28 untreated (PC) and 13 castration resistant prostate cancers (CRPC). AR, TGF-β and WNT signaling pathways were altered in CRPCs. We identified two new fusion genes, TMPRSS2-SKIL and DOT1L-HES6. Fusion analysis in an independent cohort validated SKIL as a recurrent 3’ fusion partner and oncogene in prostate cancer. The HES6 fusion was found in an AR-negative CRPC, and HES6 overexpression in vitro led to androgen independent growth. A distinct DNA methylation signature was found for CRPC. Transcriptome assembly uncovered 128 previously unannotated prostate cancer associated transcripts, including the ERG regulated transcript TPCAT-10-36067 whose knockdown had a dramatic effect on the growth, invasiveness, and rate of apoptosis of prostate cancer cells.","abstract":"We report the integrative sequencing of genomic, transcriptomic and DNA methylation changes in 28 untreated (PC) and 13 castration resistant prostate cancers (CRPC). AR, TGF-β and WNT signaling pathways were altered in CRPCs. We identified two new fusion genes, TMPRSS2-SKIL and DOT1L-HES6. Fusion analysis in an independent cohort validated SKIL as a recurrent 3’ fusion partner and oncogene in prostate cancer. The HES6 fusion was found in an AR-negative CRPC, and HES6 overexpression in vitro led to androgen independent growth. A distinct DNA methylation signature was found for CRPC. Transcriptome assembly uncovered 128 previously unannotated prostate cancer associated transcripts, including the ERG regulated transcript TPCAT-10-36067 whose knockdown had a dramatic effect on the growth, invasiveness, and rate of apoptosis of prostate cancer cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-06-03T18:50:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000527","title":"Testing the AF v4.0","description":"Testing the AF v4.0, all being well it will be brilliant!","abstract":"Testing the AF v4.0, all being well it will be brilliant!","study_type":"Other","pubmed_ids":[23734083],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000528","title":"Tagmentation-based Whole Genome Bisulfite Sequencing","description":"We demonstrated the reliability of the tagmentation-based whole genome bisulfite sequencing in direct comparison with the conventional  whole genome bisulfite sequencing.","abstract":"We demonstrated the reliability of the tagmentation-based whole genome bisulfite sequencing in direct comparison with the conventional  whole genome bisulfite sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-06-05T16:35:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000530","title":"Whole_exome_sequencing_of_inflammatory_bowel_disease_cases","description":"Whole exome sequencing of around 700 inflammatory bowel disease cases.","abstract":"Whole exome sequencing of around 700 inflammatory bowel disease cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-06-10T09:37:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000531","title":"Exome_sequence_of_probands_in_Barrett_s_oesophagus_families","description":"Barrett?s oesophagus is common in the UK affecting 2 % of the population. Family history has beenrecorded among the 4000 Barrett's cases collected so far and have 241 families. Among them wehave assessed 6 multiplex families with proven Barrett?s and defined as having 1 pro band and atleast 3 affected first degree members. We propose to exome sequence the probands of these sixfamilies to assess the presence of pathogenic rare coding variants.","abstract":"Barrett?s oesophagus is common in the UK affecting 2 % of the population. Family history has beenrecorded among the 4000 Barrett's cases collected so far and have 241 families. Among them wehave assessed 6 multiplex families with proven Barrett?s and defined as having 1 pro band and atleast 3 affected first degree members. We propose to exome sequence the probands of these sixfamilies to assess the presence of pathogenic rare coding variants.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-06-10T12:46:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000532","title":"Chromosome Y Philogeny in Sardinia","description":"Genetic variation within the male specific portion of the Y chromosome (MSY) can clarify the origins of contemporary populations, but previous studies were hampered by partial genetic information. Population sequencing of 1,204 Sardinian males identified 11,763 MSY single nucleotide polymorphisms (SNPs), of which 6,751 have not previously been observed. We constructed a MSY phylogenetic tree containing all main haplogroups found in Europe along with many Sardinian-specific lineage clusters within each haplogroup. The tree was calibrated with archaeological data from the initial expansion of the Sardinian population ~7,700 years ago. The ages of nodes highlight different genetic strata in Sardinia and reveal presumptive timing of  coalescence with other human populations. We calculate a putative age for coalescence of ~180-200,000 years ago, consistent with previous mitochondrial DNA (mtDNA) based estimates.","abstract":"Genetic variation within the male specific portion of the Y chromosome (MSY) can clarify the origins of contemporary populations, but previous studies were hampered by partial genetic information. Population sequencing of 1,204 Sardinian males identified 11,763 MSY single nucleotide polymorphisms (SNPs), of which 6,751 have not previously been observed. We constructed a MSY phylogenetic tree containing all main haplogroups found in Europe along with many Sardinian-specific lineage clusters within each haplogroup. The tree was calibrated with archaeological data from the initial expansion of the Sardinian population ~7,700 years ago. The ages of nodes highlight different genetic strata in Sardinia and reveal presumptive timing of  coalescence with other human populations. We calculate a putative age for coalescence of ~180-200,000 years ago, consistent with previous mitochondrial DNA (mtDNA) based estimates.","study_type":"Other","pubmed_ids":[23908240],"external_links":null,"is_released":true,"released_date":"2013-06-10T14:19:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000533","title":"Chondromyxoid_fibroma","description":"Chondromxoid fibroma is a benign tumour of bone with unknown underlying pathogenesis. To determine pathognomic genomic event in chondromyxoid fibroma whole genome sequencing will be undertaken to reconstruct rearrangements and find underlying mutations.","abstract":"Chondromxoid fibroma is a benign tumour of bone with unknown underlying pathogenesis. To determine pathognomic genomic event in chondromyxoid fibroma whole genome sequencing will be undertaken to reconstruct rearrangements and find underlying mutations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-06-11T17:39:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000534","title":"Analysis of DNA methylation in normal B cells and chronic lymphocytic leukemia","description":"Charting differences between tumors and normal tissue is a mainstay of cancer research. However, clonal tumor expansion from complex normal tissue architectures potentially obscures cancer-specific events, including divergent epigenetic patterns. Using whole-genome bisulfite sequencing of normal B cell subsets, we observed broad epigenetic programming of selective transcription factor binding sites coincident with the degree of B cell maturation. By comparing normal B cells to malignant B cells from 268 patients with chronic lymphocytic leukemia (CLL), we showed that tumors derive largely from a continuum of maturation states reflected in normal developmental stages. Epigenetic maturation in CLL was associated with an indolent gene expression pattern and increasingly favorable clinical outcomes.As second study using these samples focued on evolution and resulting intra-tumor heterogeneity in CLL. We used 450k bead-chip arrays to study DNA methylomes in 68 chronic lymphocytic leukemia (CLL) cases, including 28 serial cases. The result establishs linked evolution of epigenetic and genetic alterations in progressive disease, revealing an important aspect of the biology of epigenetics in cancer.","abstract":"Charting differences between tumors and normal tissue is a mainstay of cancer research. However, clonal tumor expansion from complex normal tissue architectures potentially obscures cancer-specific events, including divergent epigenetic patterns. Using whole-genome bisulfite sequencing of normal B cell subsets, we observed broad epigenetic programming of selective transcription factor binding sites coincident with the degree of B cell maturation. By comparing normal B cells to malignant B cells from 268 patients with chronic lymphocytic leukemia (CLL), we showed that tumors derive largely from a continuum of maturation states reflected in normal developmental stages. Epigenetic maturation in CLL was associated with an indolent gene expression pattern and increasingly favorable clinical outcomes.As second study using these samples focued on evolution and resulting intra-tumor heterogeneity in CLL. We used 450k bead-chip arrays to study DNA methylomes in 68 chronic lymphocytic leukemia (CLL) cases, including 28 serial cases. The result establishs linked evolution of epigenetic and genetic alterations in progressive disease, revealing an important aspect of the biology of epigenetics in cancer.","study_type":"Other","pubmed_ids":[24356097,26780610],"external_links":null,"is_released":true,"released_date":"2013-06-12T12:15:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000535","title":"Noninvasive and serial fetal methylome analysis by genome-wide maternal plasma DNA bisulfite-sequencing","description":"Epigenetic mechanisms play an important role in embryonic and fetal development. However, human embryonic and fetal tissues are not readily accessible. Cell-free fetal DNA molecules are present in maternal circulation. We applied genome-wide bisulfite sequencing to analyze the methylation profile of maternal plasma DNA at single nucleotide resolution. By exploiting the polymorphic differences between the mother and the fetus, we showed that genome scale fetal methylomic analysis could be performed using maternal blood samples. Due to the noninvasive nature of this approach, we were able to serially assess the fetal and maternal plasma methylomes from maternal blood samples collected in the first trimester, third trimester and after delivery. Gestation-related changes were observed. The fetal methylome deduced from maternal plasma resembled the placental methylome both on a genome-wide level as well as on a per CpG site basis. Imprinted genes and differentially methylated regions were identified from the maternal plasma data. We demonstrated one potential clinical application of maternal plasma bisulfite sequencing with the successful detection of fetal trisomy 21. We have therefore developed an approach to study the fetal methylome noninvasively, serially and comprehensively. This development offers a powerful method for biomarker discovery and clinical testing for pregnancy-related disorders.","abstract":"Epigenetic mechanisms play an important role in embryonic and fetal development. However, human embryonic and fetal tissues are not readily accessible. Cell-free fetal DNA molecules are present in maternal circulation. We applied genome-wide bisulfite sequencing to analyze the methylation profile of maternal plasma DNA at single nucleotide resolution. By exploiting the polymorphic differences between the mother and the fetus, we showed that genome scale fetal methylomic analysis could be performed using maternal blood samples. Due to the noninvasive nature of this approach, we were able to serially assess the fetal and maternal plasma methylomes from maternal blood samples collected in the first trimester, third trimester and after delivery. Gestation-related changes were observed. The fetal methylome deduced from maternal plasma resembled the placental methylome both on a genome-wide level as well as on a per CpG site basis. Imprinted genes and differentially methylated regions were identified from the maternal plasma data. We demonstrated one potential clinical application of maternal plasma bisulfite sequencing with the successful detection of fetal trisomy 21. We have therefore developed an approach to study the fetal methylome noninvasively, serially and comprehensively. This development offers a powerful method for biomarker discovery and clinical testing for pregnancy-related disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000536","title":"Identification of point mutations, expression perturbations, and gene fusions in T-cell acute lymphoblastic leukemia by RNA-seq","description":"RNA-seq is a promising technology to re-sequence protein-coding genes for the identification of single nucleotide variants, while simultaneously obtaining information on structural variations and gene expression perturbations. T-cell acute lymphoblastic leukemia (T-ALL) is caused by a combination of gene fusions leading to the over-expression of transcription factors reinforced by point mutations in oncogenes and tumor suppressor genes. We asked whether RNA-seq is suitable for the detection of driver mutations in these leukemias. We analyzed 31 T-ALL patient samples and 18 T-ALL cell lines by high-coverage paired-end RNA-seq.","abstract":"RNA-seq is a promising technology to re-sequence protein-coding genes for the identification of single nucleotide variants, while simultaneously obtaining information on structural variations and gene expression perturbations. T-cell acute lymphoblastic leukemia (T-ALL) is caused by a combination of gene fusions leading to the over-expression of transcription factors reinforced by point mutations in oncogenes and tumor suppressor genes. We asked whether RNA-seq is suitable for the detection of driver mutations in these leukemias. We analyzed 31 T-ALL patient samples and 18 T-ALL cell lines by high-coverage paired-end RNA-seq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-06-14T11:51:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000544","title":"Consanguineous_families_with_CHD_KAIMRC","description":"Exome sequencing of 184 samples from consanguineous families with different congenital heart defects collected at KAIMRC, Riyadh, Saudi Arabia.","abstract":"Our collaborator, Dr  Abu-Sulaiman, head of pediatric cardiology at the King Abdulaziz Cardiac Center, in Riyadh has collected 196 samples from 63 families with at least one index case with a congenital heart defect. This is the first batch of samples of an ongoing collaboration, but will be the only batch sequenced this FY. This population has been selected to enrich for autosomal recessive monogenic causation, rather than focusing on a specific CHD phenotype, and so a broad range of CHD phenotypes are observed in these families. We propose to exome sequence 184 of these samples from 58 of these families. These  families comprise 46 parent-offspring trios; 7 families with two affected sib-pairs and both parents; 1 family of 3 affected sibs; 1 family with two affected sibs; 2 families with 1 affected sib, 1 unaffected sib and both parents; and 1 family with 1 affected sib, 2 unaffected sibs and both parents.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-06-17T15:27:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000545","title":"APCDR Uganda GWAS: Genome-wide sequence variation and susceptibility loci for cardiometabolic traits in a sub-Saharan African population (UG2G component)","description":"Genomic studies in African populations provide unique opportunities to understand disease aetiology, human genetic diversity and population history in a regional and a global context. To leverage the relative benefits of different strategies, we undertook a combined approach of genotyping and whole-genome sequencing (WGS) in a population-based study of 6,400 individuals from a geographically defined rural community in South-West Uganda. We present data from 4,778 individuals with genotypes for ~2.2 million SNPs from the Uganda GWAS resource (UGWAS), and sequence data on up to 1,978 individuals spanning 41.5M SNPs and 4.5M indels (UG2G); 343 individuals overlap between the two datasets. \nWe highlight the value of the largest sequence panel from Africa to date as a global resource for variant discovery, imputation and understanding the mutational spectrum and its clinical relevance in African populations. Alongside phenotype data, we provide a rich new genomic resource for researchers in Africa and globally.","abstract":"Genomic studies in African populations provide unique opportunities to understand disease aetiology, human genetic diversity and population history in a regional and a global context. To leverage the relative benefits of different strategies, we undertook a combined approach of genotyping and whole-genome sequencing (WGS) in a population-based study of 6,400 individuals from a geographically defined rural community in South-West Uganda. We present data from 4,778 individuals with genotypes for ~2.2 million SNPs from the Uganda GWAS resource (UGWAS), and sequence data on up to 1,978 individuals spanning 41.5M SNPs and 4.5M indels (UG2G); 343 individuals overlap between the two datasets. \nWe highlight the value of the largest sequence panel from Africa to date as a global resource for variant discovery, imputation and understanding the mutational spectrum and its clinical relevance in African populations. Alongside phenotype data, we provide a rich new genomic resource for researchers in Africa and globally.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-06-20T13:48:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000546","title":"Landscape of gene mutations in Down syndrome-related myeloid disorders","description":"To identify the spectrum of gene mutations in Down syndrome-related myeloid disorders, whole genome sequencing of 4 trio samples from TAM/AMKL/complete remission (CR) phases and whole exome sequencing of 15 TAM and 14 DS-AMKL samples were performed.","abstract":"To identify the spectrum of gene mutations in Down syndrome-related myeloid disorders, whole genome sequencing of 4 trio samples from TAM/AMKL/complete remission (CR) phases and whole exome sequencing of 15 TAM and 14 DS-AMKL samples were performed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-06-25T17:16:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000547","title":"Distinct evolutionary trajectories of primary high grade serous ovarian cancers revealed through spatial mutational profiling","description":"High-grade serous ovarian cancer (HGSC) is characterized by poor outcome, often attributed to emergence of treatment-resistant sub-clones. We sought to measure the degree of genomic diversity within primary, untreated HGSC to examine the natural state of tumor evolution prior to therapy. We performed exome sequencing, copy number analysis, targeted amplicon deep sequencing and gene expression profiling on thirty-one spatially and temporally separated HGSC tumor specimens (six patients) including ovarian masses, distant metastases, and fallopian tube lesions. We found widespread intra-tumoral variation in mutation, copy number, and gene expression profiles, with key driver alterations in genes present in only a subset of samples (e.g. PIK3CA, CTNNB1, NF1). On average, only 51.5% of mutations were present in every sample of a given case (range: 10.2% to 91.4%), with TP53 as the only somatic mutation consistently present in all samples. Complex segmental aneuploidies, such as whole genome doubling, were present in a subset of samples from the same individual, with divergent copy number changes segregating independently of point mutation acquisition. Reconstruction of evolutionary histories showed one patient with mixed HGSC and endometrioid histology with common etiologic origin in the fallopian tube and subsequent selection of different driver mutations in the histologically distinct samples. In this patient, we observed mixed cell populations in the early fallopian tube lesion, indicating diversity arises at early stages of tumorigenesis. Our results reveal that HGSC exhibit highly individual evolutionary trajectories and diverse genomic tapestries prior to therapy, exposing an essential biological characteristic to inform future design of personalized therapeutic solutions and investigation of drug resistance mechanisms.","abstract":"High-grade serous ovarian cancer (HGSC) is characterized by poor outcome, often attributed to emergence of treatment-resistant sub-clones. We sought to measure the degree of genomic diversity within primary, untreated HGSC to examine the natural state of tumor evolution prior to therapy. We performed exome sequencing, copy number analysis, targeted amplicon deep sequencing and gene expression profiling on thirty-one spatially and temporally separated HGSC tumor specimens (six patients) including ovarian masses, distant metastases, and fallopian tube lesions. We found widespread intra-tumoral variation in mutation, copy number, and gene expression profiles, with key driver alterations in genes present in only a subset of samples (e.g. PIK3CA, CTNNB1, NF1). On average, only 51.5% of mutations were present in every sample of a given case (range: 10.2% to 91.4%), with TP53 as the only somatic mutation consistently present in all samples. Complex segmental aneuploidies, such as whole genome doubling, were present in a subset of samples from the same individual, with divergent copy number changes segregating independently of point mutation acquisition. Reconstruction of evolutionary histories showed one patient with mixed HGSC and endometrioid histology with common etiologic origin in the fallopian tube and subsequent selection of different driver mutations in the histologically distinct samples. In this patient, we observed mixed cell populations in the early fallopian tube lesion, indicating diversity arises at early stages of tumorigenesis. Our results reveal that HGSC exhibit highly individual evolutionary trajectories and diverse genomic tapestries prior to therapy, exposing an essential biological characteristic to inform future design of personalized therapeutic solutions and investigation of drug resistance mechanisms.","study_type":"Other","pubmed_ids":[23780408,25060187],"external_links":null,"is_released":true,"released_date":"2013-06-25T18:38:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000548","title":"Sequencing_of_RNA_samples_from_haematopoietic_cells","description":"As part of the Cardiogenics collaboration we have performed an e-QTL study in monocytes and macrophages in 425 health individuals of the Cambridge BioResource. To better define the transcript landscape of both cells we wish to sequence the RNA of monocytes, macrophages and other relevant haematopoietic cells/cell lines.","abstract":"As part of the Cardiogenics collaboration we have performed an e-QTL study in monocytes and macrophages in 425 health individuals of the Cambridge BioResource. To better define the transcript landscape of both cells we wish to sequence the RNA of monocytes, macrophages and other relevant haematopoietic cells/cell lines.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000549","title":"CPC-GENE Prostate Cancer Heterogeneity Study","description":"Herein we describe a molecular portrait of potentially curable, Gleason 7 and intermediate risk prostate cancer based on genome-wide CNV profiles of 96 patients, and subsequent whole-genome sequencing of 28 tumours from 10 patients, using DNA quantities that are achievable in diagnostic biopsies (50 ng). We show that Gleason 7 cancer is highly heterogeneous at the SNV, CNV, and intra-chromosomal translocation levels, and is characterized by a very low number of recurrent SNVs but significant structural variation. We identified a novel recurrent MYCL1 amplification, which was strongly associated with TP53 deletion and prognostic for biochemical recurrence in this cohort. Moreover, we identified clear evidence of divergent tumour evolution in multi focal cancer and, in 2/5 cases evaluated, multiple tumours of independent clonal origin. Taken together, these data represent the first systematic evaluation of the differential genomics of potentially curable prostate cancer, and strongly suggest that a more robust understanding of the relationship between genetic heterogeneity and clinical outcomes is required to effectively develop biomarkers of prognosis based on tumour genomics.","abstract":"Herein we describe a molecular portrait of potentially curable, Gleason 7 and intermediate risk prostate cancer based on genome-wide CNV profiles of 96 patients, and subsequent whole-genome sequencing of 28 tumours from 10 patients, using DNA quantities that are achievable in diagnostic biopsies (50 ng). We show that Gleason 7 cancer is highly heterogeneous at the SNV, CNV, and intra-chromosomal translocation levels, and is characterized by a very low number of recurrent SNVs but significant structural variation. We identified a novel recurrent MYCL1 amplification, which was strongly associated with TP53 deletion and prognostic for biochemical recurrence in this cohort. Moreover, we identified clear evidence of divergent tumour evolution in multi focal cancer and, in 2/5 cases evaluated, multiple tumours of independent clonal origin. Taken together, these data represent the first systematic evaluation of the differential genomics of potentially curable prostate cancer, and strongly suggest that a more robust understanding of the relationship between genetic heterogeneity and clinical outcomes is required to effectively develop biomarkers of prognosis based on tumour genomics.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-06-26T13:01:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000550","title":"Deeply sequence tumour and normal genomic DNA of esophageal adenocarcinoma","description":"The esophageal project will focus on adenocarcinoma which is increasing in incidence in the UK and other developed countries and has a very poor outcome. The primary aims of this project are to deeply sequence tumour and normal genomic DNA (including the precursor condition Barrett’s esophagus when material is available) to provide a comprehensive catalogue of somatic mutations. This will be achieved through a UK-wide network of hospitals involved in a research collaboration called the OCCAMS consortium. The goal of this project is to use high quality clinical material with accurately annotated clinic-pathological, treatment and outcome data.","abstract":"The esophageal project will focus on adenocarcinoma which is increasing in incidence in the UK and other developed countries and has a very poor outcome. The primary aims of this project are to deeply sequence tumour and normal genomic DNA (including the precursor condition Barrett’s esophagus when material is available) to provide a comprehensive catalogue of somatic mutations. This will be achieved through a UK-wide network of hospitals involved in a research collaboration called the OCCAMS consortium. The goal of this project is to use high quality clinical material with accurately annotated clinic-pathological, treatment and outcome data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000551","title":"Discovery_of_resistance_mechanisms_to_the_BRAF_inhibitor_vemurafenib_in_metastatic_BRAF_mutant_melanoma","description":"Discovery of resistance mechanisms to the BRAF inhibitor vemurafenib in metastatic BRAF mutant melanoma by massively-parallel sequencing of tumour samples. Comparison of genomic characteristics of pretreatment ‘sensitive’ to recurrence ‘resistant’ tumours to identify the genetics of drug resistance.","abstract":"Discovery of resistance mechanisms to the BRAF inhibitor vemurafenib in metastatic BRAF mutant melanoma by massively-parallel sequencing of tumour samples","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-07-02T08:31:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000552","title":"Reference epigenomes generated as part of the International Human Epigenomics Consortium (IHEC)","description":"The Centre for Epigenome Mapping Technologies (CEMT) is an epigenome sequencing platform funded by the Canadian Institutes of Health Research (CIHR) and Genome BC as part of the Canadian Epigenetics, Environment and Health Research Consortium (CEEHRC). CEMT aims to produce 100 human reference epigenomes, each comprising the following datasets: whole genome; whole genome bisulfite and oxidative bisulfite; transcriptome; microRNA; and chromatin immunoprecipitation (ChIP)-seq for the core chromatin marks (H3K4me1, H3K4me3, H3K9me3, H3K27me3, H3K36me3, and H3K27ac).CEEHRC is a full member of the International Human Epigenomics Consortium (IHEC), which aims to coordinate the production of 1,000 reference maps of human epigenomes for key cellular states relevant to health and diseases. As such, all datasets submitted by the CEMT platform conform to IHEC assay standards and metadata guidelines.","abstract":"The Centre for Epigenome Mapping Technologies (CEMT) is an epigenome sequencing platform funded by the Canadian Institutes of Health Research (CIHR) and Genome BC as part of the Canadian Epigenetics, Environment and Health Research Consortium (CEEHRC). CEMT aims to produce 100 human reference epigenomes, each comprising the following datasets: whole genome; whole genome bisulfite and oxidative bisulfite; transcriptome; microRNA; and chromatin immunoprecipitation (ChIP)-seq for the core chromatin marks (H3K4me1, H3K4me3, H3K9me3, H3K27me3, H3K36me3, and H3K27ac).CEEHRC is a full member of the International Human Epigenomics Consortium (IHEC), which aims to coordinate the production of 1,000 reference maps of human epigenomes for key cellular states relevant to health and diseases. As such, all datasets submitted by the CEMT platform conform to IHEC assay standards and metadata guidelines.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-07-03T23:06:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000553","title":"Genome Diveristy in Africa Project: Khoe San WGS","description":"The Genome Diversity in Africa Project focus on sequencing the whole genome of less studied, genetically diverse groups within sub-Saharan Africa with the objective of detailed characterisation of genetic variation within Africa. African populations show the greatest genetic diversity, with genetic variation in Eurasia, Oceania and the Americas largely being a subset of the African diversity. Within Africa, click-speaking southern African San and Khoe populations have been repeatedly shown to have the greatest genomic diversity and likely represent the deepest historical population divergences among existing human populations [1]. However, these African populations are under-represented in genome-wide studies of genetic diversity, and studies assessing the ethnic diversity within the Khoe-San in southern Africa have focused on few individuals or markers within each ethnic group. The study of these groups can provide important insights into the evolutionary adaptations related to lifestyle differences and environmental factors. For instance, whole genome sequence data from a single Khoe-San individual (!Gubi) has provided important insights into the genetic diversity of indigenous hunter-gatherer in relation to Bantu populations and has revealed biologically relevant loci under selection in these groups with respect to populations that have adopted a farming lifestyle [2]. Assembly of sequence data from this individual also unveiled several genomic regions that correspond to gaps in the current understanding of the human assembly [2]. Large scale sequencing efforts of the highly diverse Khoe-San populations, besides providing unique opportunities to explore human history, would facilitate inclusion of these groups in genetic association studies of disease, rendering the latter more informative. Capturing this previously unexplored diversity would also allow the development of novel reference panels for imputation, providing a more suitable platform for imputation of rare haplotypes unique to sub-Saharan Africa, especially to South African populations, where a large proportion of Khoe-San admixture is seen. The Nama are a Khoe group distinguished by a pastoralist lifestyle in contrast to the hunter-gatherer lifestyle of the San groups; yet they show great genetic similarity to the Southern San groups, such as ?Khomani and Karretjie [1]. In this study, we plan to carry out whole Version: September 2011 Page 2 of 5 genome sequencing (4x) on samples from 110 individuals belonging to the Nama ethnic group, with the objective of examining the genetic diversity in these individuals, and differentiation of loci with respect to other African populations. These data will also contribute to a larger African reference panel for imputation incorporating whole genome sequencing data from diverse populations across Africa. We will also genotype the same individuals using the Illumina Human OmniChip 2.5M array, to provide validation of genotype calling from sequence data, as well as to provide a scaffold for better phasing and refinement of genotypes, as it has been shown previously [3]. References 1. Schlebusch CM, Skoglund P, Sjodin P, Gattepaille LM, Hernandez D, Jay F, et al. Genomic variation in seven Khoe-San groups reveals adaptation and complex African history. Science 2012,338:374-379. 2. Schuster SC, Miller W, Ratan A, Tomsho LP, Giardine B, Kasson LR, et al. Complete Khoisan and Bantu genomes from southern Africa. Nature 2010,463:943-947. 3. Menelaou A, Marchini J. Genotype calling and phasing using next-generation sequencing reads and a haplotype scaffold. Bioinformatics 2013,29:84-91.","abstract":"The Genome Diversity in Africa Project focus on sequencing the whole genome of less studied, genetically diverse groups within sub-Saharan Africa with the objective of detailed characterisation of genetic variation within Africa. African populations show the greatest genetic diversity, with genetic variation in Eurasia, Oceania and the Americas largely being a subset of the African diversity. Within Africa, click-speaking southern African San and Khoe populations have been repeatedly shown to have the greatest genomic diversity and likely represent the deepest historical population divergences among existing human populations [1]. However, these African populations are under-represented in genome-wide studies of genetic diversity, and studies assessing the ethnic diversity within the Khoe-San in southern Africa have focused on few individuals or markers within each ethnic group. The study of these groups can provide important insights into the evolutionary adaptations related to lifestyle differences and environmental factors. For instance, whole genome sequence data from a single Khoe-San individual (!Gubi) has provided important insights into the genetic diversity of indigenous hunter-gatherer in relation to Bantu populations and has revealed biologically relevant loci under selection in these groups with respect to populations that have adopted a farming lifestyle [2]. Assembly of sequence data from this individual also unveiled several genomic regions that correspond to gaps in the current understanding of the human assembly [2]. Large scale sequencing efforts of the highly diverse Khoe-San populations, besides providing unique opportunities to explore human history, would facilitate inclusion of these groups in genetic association studies of disease, rendering the latter more informative. Capturing this previously unexplored diversity would also allow the development of novel reference panels for imputation, providing a more suitable platform for imputation of rare haplotypes unique to sub-Saharan Africa, especially to South African populations, where a large proportion of Khoe-San admixture is seen. The Nama are a Khoe group distinguished by a pastoralist lifestyle in contrast to the hunter-gatherer lifestyle of the San groups; yet they show great genetic similarity to the Southern San groups, such as ?Khomani and Karretjie [1]. In this study, we plan to carry out whole Version: September 2011 Page 2 of 5 genome sequencing (4x) on samples from 110 individuals belonging to the Nama ethnic group, with the objective of examining the genetic diversity in these individuals, and differentiation of loci with respect to other African populations. These data will also contribute to a larger African reference panel for imputation incorporating whole genome sequencing data from diverse populations across Africa. We will also genotype the same individuals using the Illumina Human OmniChip 2.5M array, to provide validation of genotype calling from sequence data, as well as to provide a scaffold for better phasing and refinement of genotypes, as it has been shown previously [3]. References 1. Schlebusch CM, Skoglund P, Sjodin P, Gattepaille LM, Hernandez D, Jay F, et al. Genomic variation in seven Khoe-San groups reveals adaptation and complex African history. Science 2012,338:374-379. 2. Schuster SC, Miller W, Ratan A, Tomsho LP, Giardine B, Kasson LR, et al. Complete Khoisan and Bantu genomes from southern Africa. Nature 2010,463:943-947. 3. Menelaou A, Marchini J. Genotype calling and phasing using next-generation sequencing reads and a haplotype scaffold. Bioinformatics 2013,29:84-91.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000554","title":"Recurrent Somatic Mutations of PTPN1 in Primary Mediastinal B cell lymphoma and Hodgkin Lymphoma","description":"Hodgkin lymphoma (HL) and primary mediastinal B cell lymphoma (PMBCL) are related lymphomas sharing pathological, molecular and clinical characteristics. Here, we discovered recurrent somatic coding sequence mutations of the tyrosine phosphatase gene PTPN1 in the tumor genomes and transcriptomes of these B cell lymphomas (6 of 30 or in 20% of HL cases and 13 of 49 or in 27% of PMBCL cases), consisting of nonsense, missense and frameshift mutations. We demonstrate that PTPN1 mutations lead to reduced phosphatase activity and increased phosphorylation of JAK-STAT pathway members. Moreover, silencing of PTPN1 by RNA interference in HL cell line KM-H2 resulted in hyperphosphorylation and overexpression of downstream oncogenic targets. Our data establish PTPN1 mutations as novel drivers in B cell lymphomagenesis.","abstract":"Hodgkin lymphoma (HL) and primary mediastinal B cell lymphoma (PMBCL) are related lymphomas sharing pathological, molecular and clinical characteristics. Here, we discovered recurrent somatic coding sequence mutations of the tyrosine phosphatase gene PTPN1 in the tumor genomes and transcriptomes of these B cell lymphomas (6 of 30 or in 20% of HL cases and 13 of 49 or in 27% of PMBCL cases), consisting of nonsense, missense and frameshift mutations. We demonstrate that PTPN1 mutations lead to reduced phosphatase activity and increased phosphorylation of JAK-STAT pathway members. Moreover, silencing of PTPN1 by RNA interference in HL cell line KM-H2 resulted in hyperphosphorylation and overexpression of downstream oncogenic targets. Our data establish PTPN1 mutations as novel drivers in B cell lymphomagenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-07-06T01:13:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000555","title":"Somatic pseudogenes acquired during cancer development","description":"Insertion of processed pseudogenes is known to occur in the germline but has not previously been observed in somatic cells. Formation of pseudogenes could represent a new class of mutation in cancers and a new source of potential driver events.","abstract":"Insertion of processed pseudogenes is known to occur in the germline but has not previously been observed in somatic cells. Formation of pseudogenes could represent a new class of mutation in cancers and a new source of potential driver events.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000556","title":"Whole genome sequencing of autism spectrum disorder","description":"Autism Spectrum Disorder (ASD) demonstrates high heritability and familial clustering, yet the genetic causes remain only partially understood as a result of extensive clinical and genomic heterogeneity. Whole-genome sequencing (WGS) shows promise as a tool for identifying ASD risk genes as well as unreported mutations in known loci, but an assessment of its full utility in an ASD group has not been performed. We used WGS to examine 32 families with ASD to detect de novo or rare inherited genetic variants predicted to be deleterious (loss-of-function and damaging missense mutations). Among ASD probands, we identified deleterious de novo mutations in six of 32 (19%) families and X-linked or autosomal inherited alterations in ten of 32 (31%) families (some had combinations of mutations). The proportion of families identified with such putative mutations was larger than has been previously reported; this yield was in part due to the comprehensive and uniform coverage afforded by WGS. Deleterious variants were found in four unrecognized, nine known, and eight candidate ASD risk genes. Examples include CAPRIN1 and AFF2 (both linked to FMR1, which is involved in fragile X syndrome), VIP (involved in social-cognitive deficits), and other genes such as SCN2A and KCNQ2 (linked to epilepsy), NRXN1, and CHD7, which causes ASD-associated CHARGE syndrome. Taken together, these results suggest that WGS and thorough bioinformatic analyses for de novo and rare inherited mutations will improve the detection of genetic variants likely to be associated with ASD or its accompanying clinical symptoms.","abstract":"Autism Spectrum Disorder (ASD) demonstrates high heritability and familial clustering, yet the genetic causes remain only partially understood as a result of extensive clinical and genomic heterogeneity. Whole-genome sequencing (WGS) shows promise as a tool for identifying ASD risk genes as well as unreported mutations in known loci, but an assessment of its full utility in an ASD group has not been performed. We used WGS to examine 32 families with ASD to detect de novo or rare inherited genetic variants predicted to be deleterious (loss-of-function and damaging missense mutations). Among ASD probands, we identified deleterious de novo mutations in six of 32 (19%) families and X-linked or autosomal inherited alterations in ten of 32 (31%) families (some had combinations of mutations). The proportion of families identified with such putative mutations was larger than has been previously reported; this yield was in part due to the comprehensive and uniform coverage afforded by WGS. Deleterious variants were found in four unrecognized, nine known, and eight candidate ASD risk genes. Examples include CAPRIN1 and AFF2 (both linked to FMR1, which is involved in fragile X syndrome), VIP (involved in social-cognitive deficits), and other genes such as SCN2A and KCNQ2 (linked to epilepsy), NRXN1, and CHD7, which causes ASD-associated CHARGE syndrome. Taken together, these results suggest that WGS and thorough bioinformatic analyses for de novo and rare inherited mutations will improve the detection of genetic variants likely to be associated with ASD or its accompanying clinical symptoms.","study_type":"Other","pubmed_ids":[23849776],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000557","title":"Whole exome sequencing of peripheral T-cell lymphoma (PTCL)","description":"Somatic mutations in 3 AITL and 3 PTCL, not otherwise specified (PTCL-NOS) specimens were explored using whole-exome sequencing.","abstract":"Somatic mutations in 3 AITL and 3 PTCL, not otherwise specified (PTCL-NOS) specimens were explored using whole-exome sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-07-10T02:43:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000558","title":"DNA from colon cancer samples and matched normal samples was hybridized on Human 660W-Quad SNP arrays and sequenced in Illumina HiScanSQ.","description":"DNA from colon cancer samples and matched normal samples was hybridized on Human 660W-Quad SNP arrays and sequenced in Illumina HiScanSQ. The objective of the study was to introduce methodology for the detection of genomic copy number alterations (CNAs) using high-throughput sequencing data. The samples in this study allow the comparison of the results from the seqCNA R package with those from other methods that detect copy number alterations (CNAs) in tumoural samples, either using SNP-array data or high-throughput sequencing data.","abstract":"DNA from colon cancer samples and matched normal samples was hybridized on Human 660W-Quad SNP arrays and sequenced in Illumina HiScanSQ. The objective of the study was to introduce methodology for the detection of genomic copy number alterations (CNAs) using high-throughput sequencing data. The samples in this study allow the comparison of the results from the seqCNA R package with those from other methods that detect copy number alterations (CNAs) in tumoural samples, either using SNP-array data or high-throughput sequencing data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-07-11T17:25:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000559","title":"ICGC Oesophageal adenocarcinoma - pilot samples","description":"The oesophageal project will focus on adenocarcinoma which is increasing in incidence in the UK and other developed countries and has a very poor outcome. The primary aims of this project are to deeply sequence tumour and normal genomic DNA (including the precursor condition Barrett's oesophagus when material is available) to provide a comprehensive catalogue of somatic mutations. This will be achieved through a UK-wide network of hospitals involved in a research collaboration called the OCCAMS consortium. The goal of this project is to use high quality clinical material with accurately annotated clinic-pathological, treatment and outcome data.","abstract":"The oesophageal project will focus on adenocarcinoma which is increasing in incidence in the UK and other developed countries and has a very poor outcome. The primary aims of this project are to deeply sequence tumour and normal genomic DNA (including the precursor condition Barrett's oesophagus when material is available) to provide a comprehensive catalogue of somatic mutations. This will be achieved through a UK-wide network of hospitals involved in a research collaboration called the OCCAMS consortium. The goal of this project is to use high quality clinical material with accurately annotated clinic-pathological, treatment and outcome data.","study_type":"Other","pubmed_ids":[24952744],"external_links":null,"is_released":true,"released_date":"2013-07-19T12:20:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000560","title":"targeted exome sequencing of genes in patientd with renal malformation and proteinuria or atypical Alports","description":"We applied customized targeted next-generation exome sequencing (NGS) to determine if mutations in genes associated with renal malformations, Alport syndrome (AS) or nephrotic syndrome are a potential cause of renal abnormalities in patients with equivocal or atypical presentation. In one patient 292 kidney specific genes were sequenced and potential cause of renal malformation and proteinuria was found.  In 14 other patients, 19 genes that are thought to be associated with Alports or nephrotic syndrome were sequenced using multiindexed NGS and several novel Alport mutations were found.","abstract":"We applied customized targeted next-generation exome sequencing (NGS) to determine if mutations in genes associated with renal malformations, Alport syndrome (AS) or nephrotic syndrome are a potential cause of renal abnormalities in patients with equivocal or atypical presentation. In one patient 292 kidney specific genes were sequenced and potential cause of renal malformation and proteinuria was found.  In 14 other patients, 19 genes that are thought to be associated with Alports or nephrotic syndrome were sequenced using multiindexed NGS and several novel Alport mutations were found.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000561","title":"ICGC PedBrain DNA methylation sequencing","description":"DNA methylation profiling of 107 medulloblastoma and 8 control samples by high-coverage whole-genome bisulfite (WBGS) sequencing and Illumina Infinium HumanMethylation450k array.","abstract":"DNA methylation profiling of 107 medulloblastoma and 8 control samples by high-coverage whole-genome bisulfite (WBGS) sequencing and Illumina Infinium HumanMethylation450k array.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-07-24T15:41:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000562","title":"Whole_genome_sequencing_of_a_Grem1_mutant_human_tumour","description":"The BMP antagonist Grem1 has been shown to be associated with a rare human polyposissyndrome (HMPS). We have shown that there is a 40KB duplication on chrom 15 found insome patients with HMPS. Traditional serrated adenomas (rare sporadic polyps) share somemorphological features with HMPS polyps and it has long been hypothesised that they are thesporadic version of HMPS polyps. We have obtained of one of theselesions and in this project we aim to characterise this tumour.","abstract":"The BMP antagonist Grem1 has been shown to be associated with a rare human polyposissyndrome (HMPS). We have shown that there is a 40KB duplication on chrom 15 found insome patients with HMPS. Traditional serrated adenomas (rare sporadic polyps) share somemorphological features with HMPS polyps and it has long been hypothesised that they are thesporadic version of HMPS polyps. We have obtained of one of theselesions and in this project we aim to characterise this tumour.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-07-25T10:46:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000563","title":"Comparison_of_transcriptional_response_of_induced_pluripotent_stem__iPS__cell_derived_and_monocyte_derived_macrophages_to_bacterial_lipopolysaccharide_stimulation","description":"In the first part of this project, we will differentiate IPS cells from 5 human donors into macrophages, and extract RNA from unstimulated and LPS stimulated macrophages to perform RNA sequencing. We will also extract RNA before and after stimulation in blood- derived macrophages from 5 additional, unrelated healthy samples. In the second part of the project, RNA-seq data will be analysed to compare LPS response of these two macrophage populations. In summary, we will perform 75bp PE RNA-seq on 20 samples (10 pre and post stimulus), on the HiSeq 2500 platform. Samples will be multiplexed at 5 samples / lane, so we will require 4 flow cells in total.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Macrophages are a major cell type of innate immunity that recognize and respond to various environmental stimuli, in particular invading microorganisms. Laboratory studies of human macrophage biology typically use monocyte-derived macrophages using blood samples. However, the quantity of macrophages that can be obtained using this method is limited by the number of available volunteers and the quantity of blood that can be drawn from each donor. One alternative method is to use macrophages derived in vitro from human induced pluripotent stem cells (hIPSCs). Methods to differentiate hIPSCs into macrophages under defined conditions [1] have recently been published and provide potentially unlimited sources of human macrophages. The availability of essentially infinite quantities of human macrophages enables a more systematic study of macrophage responses to environmental conditions and stimuli, and their interaction with genetic background. However, although IPS derived macrophages look morphologically similar to monocyte derived macrophages (MDM?) and express specific cell surface markers [1], there has not been a systematic comparison of the transcriptional response of IPS and blood-derived macrophages to a defined environmental stimuli. Comparison of the IPS-derived macrophage response with that of the standard macrophage model is an important step in establishing hIPSC –based model system as an alternative to MDM?s.Lipopolysaccharide (LPS) is a major component of Gram-negative bacteria that induce a potent transcriptional response in macrophages. Macrophage receptors that recognize LPS and downstream signaling pathways are well characterized. The aim of this project is to compare transcriptional response of IPS-derived and blood-derived macrophages after LPS treatment.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-07-25T15:50:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000564","title":"Lymphocyte_RNA_profiling","description":"This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"In a recent EWAS study of 354 blood samples profiled with the methylation 450K array we identified 15 loci showing differential methylation significantly associated with smoking (manuscript in preparation). In one of the loci we identified a metQTL SNP which we subsequently have shown to interact with smoking to affect methylation levels. Interestingly, this metSNP is also an eQTL SNP for a cholinergic nicotinic receptor gene (CHRND) located some 50kb away. A puzzling observation is that in the lymphoblastoid cell lines where we detected the eQTL it appears that its presence is conditional on smoking status. Although this finding is in line with the interaction we detected for methylation it is less evident why it is present in LCLs. However, these LCLs are only first passage lines and it may be possible that they retain signatures of gene regulation. In addition to not having expression data in primary cells, another limitation in our study is that blood signals can be confounded by changes in blood cell type counts. We now have a sample of matched RNA and DNA from lymphocytes from 180 individuals of Pakistani origin which we would like to profile by RNA seq and 450K methylation array (all samples are in Cambridge). We will multiplex 6-7 RNA samples per lane and run 75-bp paired-end aiming at 40M reads per sample.  The study will assess the smoking loci we detected in Europeans in a South Asian sample and allow for better correlation between methylation and expression levels including allele specific expression. All samples have GWAS data.  It will also allow us to assess other forms of tobacco exposure and how they compare to cigarette smoking. More globaly, the study will allow to obtain a first set of eQTLs and metQTLs in primary cells in South Asians which hasn't been covered so far and will enable functional annotation of  lead GWAS SNPs in this ethnic group.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-07-26T08:47:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000565","title":"Hypermutation of the inactive X chromosome is a frequent event in cancer","description":"Mutation is a fundamental process in tumorigenesis. However the degree to which the rate of somatic mutation varies across the human genome and the mechanistic basis underlying this variation remain to be fully elucidated. As part of the ICGC PedBrain and Malignant Lymphoma (MMML-Seq) consortium we performed a cross-cancer comparison of whole genomes comprising a diverse set of childhood and adult tumors including both solid and hematopoietic malignancies. In addition we performed whole genome sequencing of clonally expanded hematopoietic stem/progenitor cells (HSPCs) from healthy individuals to compare somatic mutation rates.","abstract":"Mutation is a fundamental process in tumorigenesis. However the degree to which the rate of somatic mutation varies across the human genome and the mechanistic basis underlying this variation remain to be fully elucidated. As part of the ICGC PedBrain and Malignant Lymphoma (MMML-Seq) consortium we performed a cross-cancer comparison of whole genomes comprising a diverse set of childhood and adult tumors including both solid and hematopoietic malignancies. In addition we performed whole genome sequencing of clonally expanded hematopoietic stem/progenitor cells (HSPCs) from healthy individuals to compare somatic mutation rates.","study_type":"Other","pubmed_ids":[24139898],"external_links":null,"is_released":true,"released_date":"2013-07-26T16:06:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000566","title":"Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing","description":"Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing","abstract":"Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-07-28T02:16:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000567","title":"Autozygosity_pilot___British_Pakistani_from_Birmingham_2","description":"The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry.  In the UK there are large populations with very high first cousin marriage rates of 20-50%.  Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations.  This pilot study based on existing British-Pakistani cohort samples from Birmingham will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed.  The data deposited in the EGA consists of low coverage whole exome sequencing on these samples.","abstract":"The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry.  In the UK there are large populations with very high first cousin marriage rates of 20-50%.  Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations.  This pilot study based on existing British-Pakistani cohort samples from Birmingham will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed.  The data deposited in the EGA consists of low coverage whole exome sequencing on these samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-07-30T11:30:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000568","title":"Tumor suppressor miR-133a modulates the prostate cancer epigenome by repressing BAZ2A","description":"Our study revealed a new subgroup of prostate tumors defined by the expression of a novel prognostic marker, BAZ2A, and the first time to show the establishment of CIMP via an microRNA-epigenetic interaction in prostate tumors.","abstract":"Our study revealed a new subgroup of prostate tumors defined by the expression of a novel prognostic marker, BAZ2A, and the first time to show the establishment of CIMP via an microRNA-epigenetic interaction in prostate tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-07-31T09:52:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000569","title":"TMD_AMKL_targeted_follow_up","description":"Genomic libraries will be generated from total genomic DNA derived from 200+ patients with childhood Transient Myeloproliferative Disorder (TMD) and or Acute Megakaryocytic Leukemia (AMKL) as well some matched constitutional samples (n &lt; 50).  Libraries will be enriched for a selected panel of genes using a bespoke pulldown protocol. 96 Samples will be individually barcoded and subjected to up to two lanes of Illumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the characterisation of known gene mutations in cancer as well as the validation of potentially novel variants identified by prior exome sequencing.","abstract":"Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. We have previously used exome sequencing in 10 paired samples from patients with TMD that have progressed to AMKL. As part of this study we plan to validate these mutations in an extended cohort of 200-400 patients with TMD – AMKL to identify novel gene mutations as well as characterise: the prevalence of these mutations, contribution n in disease progression from TMD to AMKL as well as study patterns of gene –gene interactions and genotype – phenotype associations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-07-31T17:12:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000570","title":"Targeted_sequencing_of_genes_recurrently_mutated_in_AML___part2","description":"Genomic libraries will be generated from total genomic DNA derived from 4000 samples with Acute Myeloid Leukaemia. Libraries will be enriched for a selected panel of genes using a bespoke pulldown protocol. 64 Samples will be individually barcoded and subjected to up to one lanes of Illumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the characterisation of known gene mutations in cancer as well as the validation of potentially novel variants identified by prior exome sequencing.","abstract":"Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Systematic screens of AML genomes and related neoplasms have generated a catalogue of acquired gene mutations in AML and related myeloid neoplasms. To evaluate how these mutations operate in the initiation of AML and how these dicated clinical phenotyp we plan to sequence 4000 well annotated clinical samples for a selected panel of genes to study the prevalence of these mutations, contribution n in disease outcome, study patterns of gene –gene interactions and genotype – phenotype associations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-07-31T17:22:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000571","title":"POT1_splice_site_mutant_analysis","description":"We are interested in the contribution mutations in the Shelterin complex protein POT1 may have to the development of melanoma. We have identified a patient who carries a splice site mutation in POT1 and as part of our analysis of this gene we aim to sequence the transcriptome of this patient to see how this mutation influences splicing. RNA has been obtained from lymphocytes collected from the patient.","abstract":"We are interested in the contribution mutations in the Shelterin complex protein POT1 may have to the development of melanoma. We have identified a patient who carries a splice site mutation in POT1 and as part of our analysis of this gene we aim to sequence the transcriptome of this patient to see how this mutation influences splicing. RNA has been obtained from lymphocytes collected from the patient.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-08-01T09:51:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000572","title":"Whole genome sequencing of tumour and normal paired samples of diffuse intrinsic pontine gliomas","description":"Diffuse intrinsic pontine glioma (DIPG) have a universally dismal prognosis (median 9-12 months), with neither chemotherapeutic nor targeted agents showing any substantial survival benefit in clinical trials in children with these tumours. DIPG are highly infiltrative malignant glial neoplasms of the ventral pons, which due to their location within the brain, make them unsuitable for surgical resection and consequently have a universally dismal clinical outcome. Recent high-throughput sequencing approaches have revealed a striking prevalence of K27M mutations in the genes encoding the histone variants H3.3 (H3F3A) or H3.1 (HIST1H3B) in the childhood brain tumour DIPG. This K-to-M substitution confers a trans-dominant ablation of global H3K27 trimethylation, which likely profoundly alters gene expression through de-repression of polycomb repressive complex 2 (PRC2) target genes. Despite these advances in our understanding of the distinct biology of these tumours, approaches for specific novel therapeutic interventions are not clear, and little has been reported of the secondary mutations accompanying these changes. We carried out whole genome sequencing on a series of 20 tumour normal pairs of pre-treatment biopsy samples of DIPG, for which the patients underwent a safe stereotactic procedure, and whole exome sequencing on a further six tumour normal pairs obtained at autopsy.","abstract":"Diffuse intrinsic pontine glioma (DIPG) have a universally dismal prognosis (median 9-12 months), with neither chemotherapeutic nor targeted agents showing any substantial survival benefit in clinical trials in children with these tumours. DIPG are highly infiltrative malignant glial neoplasms of the ventral pons, which due to their location within the brain, make them unsuitable for surgical resection and consequently have a universally dismal clinical outcome. Recent high-throughput sequencing approaches have revealed a striking prevalence of K27M mutations in the genes encoding the histone variants H3.3 (H3F3A) or H3.1 (HIST1H3B) in the childhood brain tumour DIPG. This K-to-M substitution confers a trans-dominant ablation of global H3K27 trimethylation, which likely profoundly alters gene expression through de-repression of polycomb repressive complex 2 (PRC2) target genes. Despite these advances in our understanding of the distinct biology of these tumours, approaches for specific novel therapeutic interventions are not clear, and little has been reported of the secondary mutations accompanying these changes. We carried out whole genome sequencing on a series of 20 tumour normal pairs of pre-treatment biopsy samples of DIPG, for which the patients underwent a safe stereotactic procedure, and whole exome sequencing on a further six tumour normal pairs obtained at autopsy.","study_type":"Other","pubmed_ids":[24705252],"external_links":null,"is_released":true,"released_date":"2013-08-01T17:31:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000573","title":"Process Control for DNA Sequencing Experiments: Modelling Library Complexity","description":"As next-generation sequencing (NGS) continues to increase in speed and throughput, routine clinical and industrial applications draw steadily closer. These “production” uses of NGS will require enhanced quality-monitoring and quality–control to optimize output while reducing costs.","abstract":"As next-generation sequencing (NGS) continues to increase in speed and throughput, routine clinical and industrial applications draw steadily closer. These “production” uses of NGS will require enhanced quality-monitoring and quality–control to optimize output while reducing costs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000574","title":"A sequence-based genetic dissection of human immune cell types and implications for immune-related disease.","description":"The immune system is an intricate biological network mediating interactions with other organisms while preserving the integrity of our tissues. By mounting appropriate responses it protects us from a vast range of pathogens while inadvertent immune system attacks on self result in autoimmune diseases. The project aims to discover whether and to what extent the behaviour of the immune system is genetically regulated and to detect the relationships of diverse immune cells with autoimmunity. The project consists of the genetic analysis using up to ~8.2 Million variants, deriving from high density genotyping data and low pass whole genome sequencing, and quantitative levels of 95 cell types encompassing 272 immune traits, in a cohort of 1,629 individuals from four clustered Sardinian villages belonging to the SardiNIA/ProgeNIA study.","abstract":"The immune system is an intricate biological network mediating interactions with other organisms while preserving the integrity of our tissues. By mounting appropriate responses it protects us from a vast range of pathogens while inadvertent immune system attacks on self result in autoimmune diseases. The project aims to discover whether and to what extent the behaviour of the immune system is genetically regulated and to detect the relationships of diverse immune cells with autoimmunity. The project consists of the genetic analysis using up to ~8.2 Million variants, deriving from high density genotyping data and low pass whole genome sequencing, and quantitative levels of 95 cell types encompassing 272 immune traits, in a cohort of 1,629 individuals from four clustered Sardinian villages belonging to the SardiNIA/ProgeNIA study.","study_type":"Other","pubmed_ids":[24074872],"external_links":null,"is_released":true,"released_date":"2013-08-07T15:31:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000575","title":"Whole genome sequencing and whole exome sequencing of DIPG tumors and matched normal tissue","description":"Diffuse Intrinsic Pontine Glioma (DIPG) is a fatal brain cancer that arises in the brainstem of children with no effective treatment. To understand what drives DIPGs we integrated whole-genome-sequencing with methylation, expression and copy-number profiling.","abstract":"Diffuse Intrinsic Pontine Glioma (DIPG) is a fatal brain cancer that arises in the brainstem of children with no effective treatment. To understand what drives DIPGs we integrated whole-genome-sequencing with methylation, expression and copy-number profiling.","study_type":"Other","pubmed_ids":[24705254],"external_links":null,"is_released":true,"released_date":"2013-08-08T17:56:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000576","title":"Exome sequencing reveals HINT1 mutations as a cause of distal hereditary motor neuropathy","description":"Distal hereditary motor neuropathies (dHMN) are a heterogeneous group of genetic disorders with length-dependent degeneration of motor axons. Obtaining a genetic diagnosis in patients with dHMN remains challenging. We performed exome sequencing in a diagnostic setting in 12 patients with a clinical diagnosis of dHMN. Potential disease-causing variants in genes associated with dHMN and other forms of inherited neuropathies/motor neuron diseases were validated using Sequenom. The coverage in the genes studied was &gt; 95% with an average coverage of &gt; 50 times. In none of the patients a mutations was found in genes previously reported to be associated with dHMN. However, in 2/12 patients a recessive mutation in histidine triad nucleotide binding protein 1 (HINT1, recently discovered as cause of axonal neuropathy with neuromyotonia) was identified. Our results demonstrate the diagnostic value of exome sequencing for patients with inherited neuropathies. The phenotypic spectrum of recessive mutations in HINT1 includes dHMN. HINT1 should be added to the list of genes to check for in dHMN.","abstract":"Distal hereditary motor neuropathies (dHMN) are a heterogeneous group of genetic disorders with length-dependent degeneration of motor axons. Obtaining a genetic diagnosis in patients with dHMN remains challenging. We performed exome sequencing in a diagnostic setting in 12 patients with a clinical diagnosis of dHMN. Potential disease-causing variants in genes associated with dHMN and other forms of inherited neuropathies/motor neuron diseases were validated using Sequenom. The coverage in the genes studied was &gt; 95% with an average coverage of &gt; 50 times. In none of the patients a mutations was found in genes previously reported to be associated with dHMN. However, in 2/12 patients a recessive mutation in histidine triad nucleotide binding protein 1 (HINT1, recently discovered as cause of axonal neuropathy with neuromyotonia) was identified. Our results demonstrate the diagnostic value of exome sequencing for patients with inherited neuropathies. The phenotypic spectrum of recessive mutations in HINT1 includes dHMN. HINT1 should be added to the list of genes to check for in dHMN.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000577","title":"Replication_and_fine_mapping_of_genome_wide_associated_loci_for_podoconiosis_Exome_sequencing","description":"BackgroundPodoconiosis (endemic, non-filarial elephantiasis) is a tropical lymphoedema resulting from long-term barefoot exposure to red clay soil derived from volcanic rock. WHO has recently recognized it as a Neglected Tropical Disease (NTD) which causes overwhelming economic and social burdens in impoverished communities. Only a subset of exposed individuals develops podoconiosis. Consistent with a genetic aetiology, our previous studies indicated high heritability (~63%) and autosomal co-dominant major gene inheritance. A genome-wide association study (GWAS) with 194 cases and 203 controls from southern Ethiopia was recently conducted by the PI of the proposed gant. Findings were validated using family-based association testing among 202 family trios and HLA typing in 94 cases and 94 controls.  Genomewide significant association of podoconiosis with rs17612858, located 5.7kb from HLA-DQA1 (OR=2.44, 95% CI = 1.82-3.26, P =1.42 x 10-9 in the allelic model), and suggestive associations (P&lt;1.0x10-5) with 7 SNPs in or near HLA-DQB1, HLA-DQA1 and HLA-DRB1 were found. These associations were confirmed using family-based association testing. HLA analysis showed HLA-DRB1*0701 (OR =2.0), DQA1*0201 (OR=1.91) and DQB1*0202 (OR=1.79) alleles and the DRB1*0701-DQB1*0202 haplotype (OR=1.92) were risk variants for podoconiosis.Proposed workWe are seeking funding from the MRC to:i) extend the podoconiosis bioresource to include a further 600 samples from the GWAS population in southern Ethiopia, 1600 samples from 2 ethnically distinct Ethiopian populations in Ethiopia and 800 samples from Cameroonii) confirm associations identified in the initial GWAS by typing associated SNPs in each of these populations;iii) perform high resolution HLA Class II typing of cases, family members and controls;iv) sequence 200 whole exomesv) fine map the region using these population-specific variants to identify putative causal variants.We plan to carry out the experiments for ii. and iv. at the Sanger.","abstract":"BackgroundPodoconiosis (endemic, non-filarial elephantiasis) is a tropical lymphoedema resulting from long-term barefoot exposure to red clay soil derived from volcanic rock. WHO has recently recognized it as a Neglected Tropical Disease (NTD) which causes overwhelming economic and social burdens in impoverished communities. Only a subset of exposed individuals develops podoconiosis. Consistent with a genetic aetiology, our previous studies indicated high heritability (~63%) and autosomal co-dominant major gene inheritance. A genome-wide association study (GWAS) with 194 cases and 203 controls from southern Ethiopia was recently conducted by the PI of the proposed gant. Findings were validated using family-based association testing among 202 family trios and HLA typing in 94 cases and 94 controls.  Genomewide significant association of podoconiosis with rs17612858, located 5.7kb from HLA-DQA1 (OR=2.44, 95% CI = 1.82-3.26, P =1.42 x 10-9 in the allelic model), and suggestive associations (P&lt;1.0x10-5) with 7 SNPs in or near HLA-DQB1, HLA-DQA1 and HLA-DRB1 were found. These associations were confirmed using family-based association testing. HLA analysis showed HLA-DRB1*0701 (OR =2.0), DQA1*0201 (OR=1.91) and DQB1*0202 (OR=1.79) alleles and the DRB1*0701-DQB1*0202 haplotype (OR=1.92) were risk variants for podoconiosis.Proposed workWe are seeking funding from the MRC to:i) extend the podoconiosis bioresource to include a further 600 samples from the GWAS population in southern Ethiopia, 1600 samples from 2 ethnically distinct Ethiopian populations in Ethiopia and 800 samples from Cameroonii) confirm associations identified in the initial GWAS by typing associated SNPs in each of these populations;iii) perform high resolution HLA Class II typing of cases, family members and controls;iv) sequence 200 whole exomesv) fine map the region using these population-specific variants to identify putative causal variants.We plan to carry out the experiments for ii. and iv. at the Sanger.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000578","title":"Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M-mutant pediatric high-grade gliomas","description":"Genome-wide analysis of H3K27me3 occupancy and DNA methylation in K27M-mutant and H3.3-WT primary pediatric high-grade gliomas (pHGGs) as well as pediatric pHGG cell lines. The study aims to elucidate the connection between K27M-induced H3K27me3 reduction and changes in DNA methylation as well as gene expression.","abstract":"Genome-wide analysis of H3K27me3 occupancy and DNA methylation in K27M-mutant and H3.3-WT primary pediatric high-grade gliomas (pHGGs) as well as pediatric pHGG cell lines. The study aims to elucidate the connection between K27M-induced H3K27me3 reduction and changes in DNA methylation as well as gene expression.","study_type":"Other","pubmed_ids":[24183680],"external_links":null,"is_released":true,"released_date":"2013-09-11T09:31:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000579","title":"Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma","description":"Tumor recurrence is a leading cause of cancer mortality. Therapies for recurrent disease may fail, at least in part, because the genomic alterations driving the growth of recurrences are distinct from those in the initial tumor. To explore this hypothesis, we sequenced the exomes of 23 initial low-grade gliomas and recurrent tumors resected from the same patients. In 43% of cases, at least half of the mutations in the initial tumor were undetected at recurrence, including driver mutations inTP53, ATRX, SMARCA4, and BRAF; this suggests that recurrent tumors are often seeded by cells derived from the initial tumor at a very early stage of their evolution. Notably, tumors from 6 of 10 patients treated with the chemotherapeutic drug temozolomide (TMZ) followed an alternative evolutionary path to high-grade glioma. At recurrence, these tumors were hypermutated and harbored driver mutations in the RB (retinoblastoma) and Akt-mTOR (mammalian target of rapamycin) pathways that bore the signature of TMZ-induced mutagenesis.","abstract":"Tumor recurrence is a leading cause of cancer mortality. Therapies for recurrent disease may fail, at least in part, because the genomic alterations driving the growth of recurrences are distinct from those in the initial tumor. To explore this hypothesis, we sequenced the exomes of 23 initial low-grade gliomas and recurrent tumors resected from the same patients. In 43% of cases, at least half of the mutations in the initial tumor were undetected at recurrence, including driver mutations inTP53, ATRX, SMARCA4, and BRAF; this suggests that recurrent tumors are often seeded by cells derived from the initial tumor at a very early stage of their evolution. Notably, tumors from 6 of 10 patients treated with the chemotherapeutic drug temozolomide (TMZ) followed an alternative evolutionary path to high-grade glioma. At recurrence, these tumors were hypermutated and harbored driver mutations in the RB (retinoblastoma) and Akt-mTOR (mammalian target of rapamycin) pathways that bore the signature of TMZ-induced mutagenesis.","study_type":"Exome Sequencing","pubmed_ids":[24336570],"external_links":null,"is_released":true,"released_date":"2013-09-13T02:01:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000580","title":"Whole genome sequencing of metastatic melanomas from a patient with primary resistance to BRAF inhibition","description":"Here, we investigated the underlying cause of treatment failure in a patient with BRAF mutant melanoma who presented primary resistance.  We used whole-genome sequencing (WGS) to characterise five metastatic tumours from a BRAF mutant melanoma patient who presented intrinsic resistance.","abstract":"Here, we investigated the underlying cause of treatment failure in a patient with BRAF mutant melanoma who presented primary resistance.  We used whole-genome sequencing (WGS) to characterise five metastatic tumours from a BRAF mutant melanoma patient who presented intrinsic resistance.","study_type":"Other","pubmed_ids":[3999800],"external_links":null,"is_released":true,"released_date":"2013-09-17T14:11:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000581","title":"Blueprint_Human_Variation_Project____Whole_genome_sequencing","description":"The BLUEPRINT project is a large-scale project investigating epigenetic mechanisms involved in blood formation, in health and disease. The  human variation workpackage (WP10, led by NS) of the project seeks to characterize the effect of common sequence variation on the epigenome status of a cell. To do this, the project will use highly purified blood cells to minimise “experimental noise” and therefore enhance the power to discover modest effects.  Two peripheral blood cell types, the CD14+CD16- monocyte (an important central orchestrator of adaptive immunity and a bridge between innate and adaptive immunity) and the CD65+CD9- neutrophilic granulocyte (the frontline cell for innate immunity) have been selected for this purpose.  The two types of cells will be obtained at high purity from adult blood (AB) of 200 healthy males and females, respectively.  Cells will be purified by using already validated and fully operational protocols that are based on density gradient centrifugation of the buffy coat obtained from whole blood, followed by magnetic bead-based purification using monoclonal antibodies against Cluster of Differentiation (CD) lineage-specific cell surface markers.  Units of 475 ml of AB will be obtained from consenting volunteers of the Cambridge BioResource (CBR), a panel of 10,000 healthy volunteers local to Cambridge who have already consented to participate in biomedical research and of whom biological samples (DNA, plasma, serum) and lifestyle data have been deposited in a repository and database, respectively.   Nuclei, DNA and RNA will be recovered from the purified cells and made available for RNA-seq, DNA-seq and ChIP-seq and genomic DNA for entire genome sequencing will be recovered from the DNA repository. This dataset contains the whole-genome sequence of the 200 CBR volunteers at low pass (6x coverage).","abstract":"The BLUEPRINT project is a large-scale project investigating epigenetic mechanisms involved in blood formation, in health and disease. The  human variation workpackage (WP10, led by NS) of the project seeks to characterize the effect of common sequence variation on the epigenome status of a cell. To do this, the project will use highly purified blood cells to minimise “experimental noise” and therefore enhance the power to discover modest effects.  Two peripheral blood cell types, the CD14+CD16- monocyte (an important central orchestrator of adaptive immunity and a bridge between innate and adaptive immunity) and the CD65+CD9- neutrophilic granulocyte (the frontline cell for innate immunity) have been selected for this purpose.  The two types of cells will be obtained at high purity from adult blood (AB) of 200 healthy males and females, respectively.  Cells will be purified by using already validated and fully operational protocols that are based on density gradient centrifugation of the buffy coat obtained from whole blood, followed by magnetic bead-based purification using monoclonal antibodies against Cluster of Differentiation (CD) lineage-specific cell surface markers.  Units of 475 ml of AB will be obtained from consenting volunteers of the Cambridge BioResource (CBR), a panel of 10,000 healthy volunteers local to Cambridge who have already consented to participate in biomedical research and of whom biological samples (DNA, plasma, serum) and lifestyle data have been deposited in a repository and database, respectively.   Nuclei, DNA and RNA will be recovered from the purified cells and made available for RNA-seq, DNA-seq and ChIP-seq and genomic DNA for entire genome sequencing will be recovered from the DNA repository. This dataset contains the whole-genome sequence of the 200 CBR volunteers at low pass (6x coverage).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000582","title":"Resistance to anti-EGFR therapy in colorectal cancer","description":"Monoclonal antibodies targeting the Epidermal Growth Factor Receptor (EGFR), such as cetuximab and panitumumab, have evolved to important therapeutic options in metastatic colorectal cancer (CRC). However, almost all patients with clinical response to anti-EGFR therapies show disease progression within a few months and little is known about mechanism and timing of resistance evolution. Here we performed whole genome sequencing of plasma DNA (plasma-Seq) from patients treated with anti-EGFR therapy. We demonstrate that development of resistance to anti-EGFR therapies is frequently associated with focal amplifications of KRAS, MET, and ERBB2. However, we also show that focal KRAS amplifications can be acquired in tumor genomes of patients under cytotoxic chemotherapy. Furthermore, we provide evidence that specific chromosomal polysomies, such as overrepresentations of 12p and 7p, harboring KRAS and EGFR, respectively, determine responsiveness to anti-EGFR therapy. In contrast, employing ultra-sensitive deep sequencing of genes associated with anti-EGFR resistance, such as KRAS, BRAF, PIK3CA, and EGFR, we did not observe the occurrence of novel, acquired mutations. Overall, whole-genome plasma DNA sequencing represents a non-invasive blood-based surrogate measure of changes in tumors. As such, plasma-Seq enables the identification of novel mutant clones and may therefore facilitate early adjustments of therapies that may delay or prevent disease progression.","abstract":"Monoclonal antibodies targeting the Epidermal Growth Factor Receptor (EGFR), such as cetuximab and panitumumab, have evolved to important therapeutic options in metastatic colorectal cancer (CRC). However, almost all patients with clinical response to anti-EGFR therapies show disease progression within a few months and little is known about mechanism and timing of resistance evolution. Here we performed whole genome sequencing of plasma DNA (plasma-Seq) from patients treated with anti-EGFR therapy. We demonstrate that development of resistance to anti-EGFR therapies is frequently associated with focal amplifications of KRAS, MET, and ERBB2. However, we also show that focal KRAS amplifications can be acquired in tumor genomes of patients under cytotoxic chemotherapy. Furthermore, we provide evidence that specific chromosomal polysomies, such as overrepresentations of 12p and 7p, harboring KRAS and EGFR, respectively, determine responsiveness to anti-EGFR therapy. In contrast, employing ultra-sensitive deep sequencing of genes associated with anti-EGFR resistance, such as KRAS, BRAF, PIK3CA, and EGFR, we did not observe the occurrence of novel, acquired mutations. Overall, whole-genome plasma DNA sequencing represents a non-invasive blood-based surrogate measure of changes in tumors. As such, plasma-Seq enables the identification of novel mutant clones and may therefore facilitate early adjustments of therapies that may delay or prevent disease progression.","study_type":"Other","pubmed_ids":[24676216],"external_links":null,"is_released":true,"released_date":"2013-09-20T09:37:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000583","title":"Landscape of somatic mutations and clonal evolution in mantle cell             lymphoma","description":"Mantle cell lymphoma (MCL) is an aggressive tumor but a subset of \n            patients may follow an indolent clinical course. To understand the mechanisms underlying \n            this biological heterogeneity, we performed whole-genome and/or -exome sequencing on 29 \n            MCL and their respective matched normal DNA, as well as 6 MCL cell lines. Novel recurrently \n            mutated genes were investigated by targeted sequencing in an independent cohort of 172 MCL \n            patients. We identified 25 significantly mutated genes, including known drivers such as ATM, \n            CCND1, and TP53, and novel mutated MCL genes such BIRC3, TLR2 and the chromatin modifiers \n            WHSC1, MLL2, and MEF2B. We also found NOTCH2 mutations as an alternative phenomenon to NOTCH1 \n            mutations in aggressive tumors with a dismal prognosis. Analysis of two simultaneous or \n            subsequent MCL samples by whole-genome/-exome (n=8) or targeted (n=19) sequencing revealed \n            subclonal heterogeneity at diagnosis in samples from different topographic sites, and \n            modulation of the initial mutational profile at the progression of the disease. \n            Some mutations were predominantly clonal or subclonal, indicating an early or late event \n            in tumor evolution, respectively. Our study identifies new molecular mechanisms contributing \n            to MCL pathogenesis and offers new potential targets for therapeutic intervention.","abstract":"Mantle cell lymphoma (MCL) is an aggressive tumor but a subset of \n            patients may follow an indolent clinical course. To understand the mechanisms underlying \n            this biological heterogeneity, we performed whole-genome and/or -exome sequencing on 29 \n            MCL and their respective matched normal DNA, as well as 6 MCL cell lines. Novel recurrently \n            mutated genes were investigated by targeted sequencing in an independent cohort of 172 MCL \n            patients. We identified 25 significantly mutated genes, including known drivers such as ATM, \n            CCND1, and TP53, and novel mutated MCL genes such BIRC3, TLR2 and the chromatin modifiers \n            WHSC1, MLL2, and MEF2B. We also found NOTCH2 mutations as an alternative phenomenon to NOTCH1 \n            mutations in aggressive tumors with a dismal prognosis. Analysis of two simultaneous or \n            subsequent MCL samples by whole-genome/-exome (n=8) or targeted (n=19) sequencing revealed \n            subclonal heterogeneity at diagnosis in samples from different topographic sites, and \n            modulation of the initial mutational profile at the progression of the disease. \n            Some mutations were predominantly clonal or subclonal, indicating an early or late event \n            in tumor evolution, respectively. Our study identifies new molecular mechanisms contributing \n            to MCL pathogenesis and offers new potential targets for therapeutic intervention.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001000584","title":"Assessing the impact of low frequency coding variants on disease risk using the Exomechip","description":"Following several rounds of Genome Wide Association (GWA) scans and subsequent meta-analyses of results multiple risk loci have been identified for many common diseases. However, in most instances the implicated common variants identified so far explain only a modest fraction of the genetic risk. In parallel to our efforts to identify the causative variants in the known loci it is necessary to assess the full spectrum of sequence variants for disease risk and in particular low frequency and rare variants that have not been tested in a comprehensive way so far. To this end an international effort by investigators who have performed whole exome sequencing in circa 12,000 individuals have assembled a set of ~250,000 exonic variants of low frequency – defined as seen in at least two studies and a minimum of three individuals (non-sysnonymous) or two individuals for SNPs altering splice sites / stop codons. The SNP content from the exome studies was complemented with additional interesting SNP sets totalling 25,000 markers (GWA tag SNPs, grid of common variants, HLA, Mitochondrial, Y-chromosome etc) and were used to generate a custom iSELECT array, the exome chip. Adequately powered association studies to test low frequency variants for association to disease risk are still very expensive if conducted by whole exome sequencing. The exome chip provides a cost efficient way to undertake such an experiment and the Wellcome Trust Cases Control Consortium will be applying this approach to eight diseases, type 1 and type 2 diabetes, coronary artery disease, hypertension, multiple sclerosis, rheumatoid arthritis, bipolar, and ankylosing spondylitis. The first objective will be to generate a large set of at least 10,000 common UK controls as analysis of lower frequency variants will require large sample sizes. This includes ~6000 samples from the 1958 Birth Cohort.","abstract":"Following several rounds of Genome Wide Association (GWA) scans and subsequent meta-analyses of results multiple risk loci have been identified for many common diseases. However, in most instances the implicated common variants identified so far explain only a modest fraction of the genetic risk. In parallel to our efforts to identify the causative variants in the known loci it is necessary to assess the full spectrum of sequence variants for disease risk and in particular low frequency and rare variants that have not been tested in a comprehensive way so far. To this end an international effort by investigators who have performed whole exome sequencing in circa 12,000 individuals have assembled a set of ~250,000 exonic variants of low frequency – defined as seen in at least two studies and a minimum of three individuals (non-sysnonymous) or two individuals for SNPs altering splice sites / stop codons. The SNP content from the exome studies was complemented with additional interesting SNP sets totalling 25,000 markers (GWA tag SNPs, grid of common variants, HLA, Mitochondrial, Y-chromosome etc) and were used to generate a custom iSELECT array, the exome chip. Adequately powered association studies to test low frequency variants for association to disease risk are still very expensive if conducted by whole exome sequencing. The exome chip provides a cost efficient way to undertake such an experiment and the Wellcome Trust Cases Control Consortium will be applying this approach to eight diseases, type 1 and type 2 diabetes, coronary artery disease, hypertension, multiple sclerosis, rheumatoid arthritis, bipolar, and ankylosing spondylitis. The first objective will be to generate a large set of at least 10,000 common UK controls as analysis of lower frequency variants will require large sample sizes. This includes ~6000 samples from the 1958 Birth Cohort.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-09-24T21:16:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000585","title":"Assessment of genomic copy number alterations in breast cancer","description":"The aim of this study was to assess genomic copy number alterations in a panel of breast cancer cell lines.  These data were used to identify common aberrations associated with breast cancer, and also to identify aberrations associated with response to therapeutic compounds.","abstract":"The aim of this study was to assess genomic copy number alterations in a panel of breast cancer cell lines.  These data were used to identify common aberrations associated with breast cancer, and also to identify aberrations associated with response to therapeutic compounds.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-09-25T09:27:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000586","title":"Determination_of_cell_specific_regulatory_enhancers_in_hematopoetic_models","description":"The BLUEPRINT project is a large-scale project investigating epigenetic mechanisms involved in blood formation, in health and disease. The human variation workpackage (WP10) of the project seeks to characterize the effect of common sequence variation on the epigenome status of a cell. To do this, the project will use highly purified blood cells to minimise “experimental noise” and therefore enhance the power to discover modest effects.  Two peripheral blood cell types, the CD14+CD16- monocyte (an important central orchestrator of adaptive immunity and a bridge between innate and adaptive immunity) and the CD65+CD9- neutrophilic granulocyte (the frontline cell for innate immunity) have been selected for this purpose.  The two types of cells will be obtained at high purity from adult blood (AB) of 200 healthy males and females, respectively.  Cells will be purified by using already validated and fully operational protocols that are based on density gradient centrifugation of the buffy coat obtained from whole blood, followed by magnetic bead-based purification using monoclonal antibodies against Cluster of Differentiation (CD) lineage-specific cell surface markers. This data set contains functional genomics data for gene expression and chromatin state.","abstract":"The BLUEPRINT project is a large-scale project investigating epigenetic mechanisms involved in blood formation, in health and disease. The human variation workpackage (WP10) of the project seeks to characterize the effect of common sequence variation on the epigenome status of a cell. To do this, the project will use highly purified blood cells to minimise “experimental noise” and therefore enhance the power to discover modest effects.  Two peripheral blood cell types, the CD14+CD16- monocyte (an important central orchestrator of adaptive immunity and a bridge between innate and adaptive immunity) and the CD65+CD9- neutrophilic granulocyte (the frontline cell for innate immunity) have been selected for this purpose.  The two types of cells will be obtained at high purity from adult blood (AB) of 200 healthy males and females, respectively.  Cells will be purified by using already validated and fully operational protocols that are based on density gradient centrifugation of the buffy coat obtained from whole blood, followed by magnetic bead-based purification using monoclonal antibodies against Cluster of Differentiation (CD) lineage-specific cell surface markers. This data set contains functional genomics data for gene expression and chromatin state.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-09-25T11:20:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000587","title":"Epi_Tax_targeted_sequencing","description":"Sequencing of 350 cancer genes in BC samples from patients treated with either Epirubicin or Paclitaxel monotherapy in the neoadjuvant setting.","abstract":"Abstract:Resistance towards chemotherapy is one of the main causes of treatment failure and death among breast cancer patients.The main objective of this project is to identify genetic mechanisms causing some breast cancer patients not to respond to a particluar type of chemotherapy (epirubicin or paclitaxel) while other patients respond very well to the same treatment.In the project we will perform targeted sequencing of 350 cancer related genes in 223 patients (109 Epirubicin-treated and 114 Paclitaxel-treated). For several of the tumours both pre- and post treatment samples will be sequenced.15 pre-samples has already been genome sequenced and 15 has been exome sequenced. All patients are from a study where patients recieved treatment with epirubicin or paclitaxel monotherapy before surgical removal of a locally advanced breast tumour, and where all patients have been subjected to objective evaluation of the response to the therapy.Subsequent to sequencing, we will analyse the data and compare with the clinical data for each patient (object response to therapy). The main aim being to identify mutations that are associated with resistance to epirubicin / paclitaxel.Identification of mutations with strong predictive value, may have a direct impact on cancer treatment since it opens the possibility for genetic testing of a tumour, and desicion on which drug is likely to work best, prior to treatment start.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-09-26T10:46:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000588","title":"Angiosarcoma_whole_exome","description":"Extension of angiosarcoma whole genome sequencing study","abstract":"We recently described a novel cancer gene in angiosarcoma and require additional data for the revision","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-09-26T11:09:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000589","title":"Angiosarcoma_targeted_pulldown_cancer_gene_panel","description":"Extension of angiosarcoma whole genome sequencing study","abstract":"We recently described a novel cancer gene in angiosarcoma and require additional data for the revision","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-09-26T11:15:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000590","title":"Angiosarcoma_RNA_sequencing","description":"Extension of angiosarcoma whole genome sequencing study","abstract":"We recently described a novel cancer gene in angiosarcoma and require additional data for the revision","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-09-26T11:24:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000591","title":"Sequencing_of_rare_human_histiocytic_tumour","description":"Sequencing of rare human histiocytic tumour","abstract":"Sequencing of rare human histiocytic tumour","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-09-26T14:29:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000592","title":"HipSci-Whole Exome sequencing-healthy volunteers","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sup-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies from healthy volunteers.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sup-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies from healthy volunteers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-09-30T17:02:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000593","title":"HipSci-RNAseq-healthy volunteers","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sup-study we perform RNAseq on iPS cells generated from skin biopsies from healthy volunteers.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sup-study we perform RNAseq on iPS cells generated from skin biopsies from healthy volunteers.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-10-02T09:50:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000594","title":"Global_gene_expression_profiles_in_whole_blood_of_humans_during_infection_with_Salmonella_Typhi","description":"To be completed soon retrospectively","abstract":"To be completed soon retrospectively","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000595","title":"Functional_characterization_of_Th17_cells___Pilot","description":"Our work in IBD genetics via GWAS and Immunochip has identified 163 genomic lociassociated with disease. We are currently following up the genetic architecture of IBD withprojects on fine-mapping from Immunochip and 1000 genomes imputation, as well as lowcoverage sequencing from the current QQ. In parallel with these further genetic experiments,we would like to begin to explore potential functional mechanisms of identified susceptibilityloci.This project is a pilot aimed at one possible cellular niche critical to IBD development: theTh17 subset of T helper cells. Existing literature suggests that these cells are an importantsubset in the development of a variety of inflammatory disorders. Genetic data support aspecific role in IBD, as nearly every gene involved in the differentiation signalling pathway forTh17 has been associated. Here we propose to generate 4 RNAseq expression profiles eachfrom five healthy volunteers: PBMCs, Th0 (naive T cells), Th17 stimulated and Th17 resting(the last two derived via negative selection after in vitro differentiation). These individuals willhave genotype data from Immunochip.The main outcomes of this pilot will be to determine the specificity of expression profilesacross different blood cell types and conditions, as well as to provide a first look at possibledifferential allele specific expression of IBD loci in different cell types and conditions. Theultimate aim if these results look promising would be to seek funding to scale up the numberof samples and include both controls and IBD cases.","abstract":"Our work in IBD genetics via GWAS and Immunochip has identified 163 genomic lociassociated with disease. We are currently following up the genetic architecture of IBD withprojects on fine-mapping from Immunochip and 1000 genomes imputation, as well as lowcoverage sequencing from the current QQ. In parallel with these further genetic experiments,we would like to begin to explore potential functional mechanisms of identified susceptibilityloci.This project is a pilot aimed at one possible cellular niche critical to IBD development: theTh17 subset of T helper cells. Existing literature suggests that these cells are an importantsubset in the development of a variety of inflammatory disorders. Genetic data support aspecific role in IBD, as nearly every gene involved in the differentiation signalling pathway forTh17 has been associated. Here we propose to generate 4 RNAseq expression profiles eachfrom five healthy volunteers: PBMCs, Th0 (naive T cells), Th17 stimulated and Th17 resting(the last two derived via negative selection after in vitro differentiation). These individuals willhave genotype data from Immunochip.The main outcomes of this pilot will be to determine the specificity of expression profilesacross different blood cell types and conditions, as well as to provide a first look at possibledifferential allele specific expression of IBD loci in different cell types and conditions. Theultimate aim if these results look promising would be to seek funding to scale up the numberof samples and include both controls and IBD cases.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000596","title":"Breast_Cancer_Sequential_Sampling_Targeted_Capture","description":"This study aims to target capture sequence regions of interest from DNA derived from breast cancer patients who received neo-adjuvant chemotherapy. All patients had multiple biopsies performed before chemotherapy. Patients who had residual disease after the course of treatment underwent a further biopsy. We aim to characterise the mutations involved.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-10-11T12:45:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000597","title":"HKU Gastric Cancer Genomics study - WGS, DNA genotyping array, expression and methylation profiling","description":"HKU Gastric Cancer Genomics study - Whole Genome Sequencing, DNA genotyping array, Expression profiling and Methylation profiling","abstract":"HKU Gastric Cancer Genomics study - Whole Genome Sequencing, DNA genotyping array, Expression profiling and Methylation profiling","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-10-12T08:26:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000598","title":"RB1 Gene Inactivation by Chromothripsis in Human Retinoblastoma","description":"Retinoblastoma is a rare childhood cancer of the developing retina. Most retinoblastomas initiate with biallelic inactivation of the RB1 gene through diverse mechanisms including point mutations, nucleotide insertions, deletions, loss of heterozygosity and promoter hypermethylation. Recently, a novel mechanism of retinoblastoma initiation was proposed. Gallie and colleagues discovered that a small proportion of retinoblastomas lack RB1 mutations and had MYCN amplification [1]. In this study, we identified recurrent chromosomal, regional and focal genomic lesions in 94 primary retinoblastomas with their matched normal DNA using SNP 6.0 chips. We also analyzed the RB1 gene mutations and compared the mechanism of RB1 inactivation to the recurrent copy number variations in the retinoblastoma genome.  In addition to the previously described focal amplification of MYCN and deletions in RB1 and BCOR, we also identified recurrent focal amplification of OTX2, a transcription factor required for retinal photoreceptor development. We identified 10 retinoblastomas in our cohort that lacked RB1 point mutations or indels. We performed whole genome sequencing on those 10 tumors and their corresponding germline DNA. In one of the tumors, the RB1 gene was unaltered, the MYCN gene was amplified and RB1 protein was expressed in the nuclei of the tumor cells. In addition, several tumors had complex patterns of structural variations and we identified 3 tumors with chromothripsis at the RB1 locus. This is the first report of chromothripsis as a mechanism for RB1 gene inactivation in cancer.","abstract":"Retinoblastoma is a rare childhood cancer of the developing retina. Most retinoblastomas initiate with biallelic inactivation of the RB1 gene through diverse mechanisms including point mutations, nucleotide insertions, deletions, loss of heterozygosity and promoter hypermethylation. Recently, a novel mechanism of retinoblastoma initiation was proposed. Gallie and colleagues discovered that a small proportion of retinoblastomas lack RB1 mutations and had MYCN amplification [1]. In this study, we identified recurrent chromosomal, regional and focal genomic lesions in 94 primary retinoblastomas with their matched normal DNA using SNP 6.0 chips. We also analyzed the RB1 gene mutations and compared the mechanism of RB1 inactivation to the recurrent copy number variations in the retinoblastoma genome.  In addition to the previously described focal amplification of MYCN and deletions in RB1 and BCOR, we also identified recurrent focal amplification of OTX2, a transcription factor required for retinal photoreceptor development. We identified 10 retinoblastomas in our cohort that lacked RB1 point mutations or indels. We performed whole genome sequencing on those 10 tumors and their corresponding germline DNA. In one of the tumors, the RB1 gene was unaltered, the MYCN gene was amplified and RB1 protein was expressed in the nuclei of the tumor cells. In addition, several tumors had complex patterns of structural variations and we identified 3 tumors with chromothripsis at the RB1 locus. This is the first report of chromothripsis as a mechanism for RB1 gene inactivation in cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-10-14T14:00:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000599","title":"Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability","description":"Genomic instability is a hallmark of human cancers, including the 5% caused by human papillomavirus (HPV). Here we report a striking association between HPV integration and adjacent host genomic structural variation in human cancer cell lines and primary tumors. Whole genome sequencing revealed HPV integrants flanking and bridging extensive host genomic amplifications and rearrangements, including deletions, inversions and chromosomal translocations. We present a model of ³looping² by which HPV integrant-mediated DNA replication and recombination may result in viral-host DNA concatemers, frequently disrupting genes involved in oncogenesis and amplifying HPV oncogenes E6 and E7. Our high-resolution results shed new light on a catastrophic process, distinct from chromothripsis and other mutational processes, by which HPV directly promotes genomic instability.","abstract":"Genomic instability is a hallmark of human cancers, including the 5% caused by human papillomavirus (HPV). Here we report a striking association between HPV integration and adjacent host genomic structural variation in human cancer cell lines and primary tumors. Whole genome sequencing revealed HPV integrants flanking and bridging extensive host genomic amplifications and rearrangements, including deletions, inversions and chromosomal translocations. We present a model of ³looping² by which HPV integrant-mediated DNA replication and recombination may result in viral-host DNA concatemers, frequently disrupting genes involved in oncogenesis and amplifying HPV oncogenes E6 and E7. Our high-resolution results shed new light on a catastrophic process, distinct from chromothripsis and other mutational processes, by which HPV directly promotes genomic instability.","study_type":"Other","pubmed_ids":[24201445],"external_links":null,"is_released":true,"released_date":"2013-10-14T20:39:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000600","title":"Measuring the level of relatedness between NGS datasets","description":"Sequencing technologies are providing increasingly detailed insight in genetic makeup are paving their way into molecular diagnostics. The field will benefit from rigorous and bias-free measures for the quality of sequence data and for the proper representation of the complexity of the original samples. While current methodologies rely on the availability of a well-characterized reference genome, we propose kMer profiling for alignment-free assessment of the quality, comparability, and complexity of sequencing datasets. We show that kMer detects technical artefacts such as high duplication rates, library chimaeras, and differences in library preparation protocols in whole-genome, whole-exome, and RNA sequencing data. Additionally, it successfully captures the complexity and diversity of microbiomes. Thus, kMer allows for a robust evaluation of the quality and complexity of sequencing data without relying on any prior information and opens the way to a more reliable biological reasoning.","abstract":"Sequencing technologies are providing increasingly detailed insight in genetic makeup are paving their way into molecular diagnostics. The field will benefit from rigorous and bias-free measures for the quality of sequence data and for the proper representation of the complexity of the original samples. While current methodologies rely on the availability of a well-characterized reference genome, we propose kMer profiling for alignment-free assessment of the quality, comparability, and complexity of sequencing datasets. We show that kMer detects technical artefacts such as high duplication rates, library chimaeras, and differences in library preparation protocols in whole-genome, whole-exome, and RNA sequencing data. Additionally, it successfully captures the complexity and diversity of microbiomes. Thus, kMer allows for a robust evaluation of the quality and complexity of sequencing data without relying on any prior information and opens the way to a more reliable biological reasoning.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-10-15T10:00:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000601","title":"Whole_exome_sequencing_for_HELIC","description":"The HELIC study has been whole genome sequencing individuals from 2 Greek isolatedpopulations at 1x depth. The genotype calling process crucially involves a VQSR stepfollowed by imputation-based refinement. We have been investigating optimal ways toincrease calling accuracy. To aid us in setting appropriate parameters for VQSR and otherQC steps, we have carried out whole exome sequencing of a small number ofHELIC samples.","abstract":"The HELIC study has been whole genome sequencing individuals from 2 Greek isolatedpopulations at 1x depth. The genotype calling process crucially involves a VQSR stepfollowed by imputation-based refinement. We have been investigating optimal ways toincrease calling accuracy. To aid us in setting appropriate parameters for VQSR and otherQC steps, we have carried out whole exome sequencing of a small number ofHELIC samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000602","title":"Whole_exome_sequencing_for_HELIC","description":"The HELIC study has been whole genome sequencing individuals from 2 Greek isolatedpopulations at 1x depth. The genotype calling process crucially involves a VQSR stepfollowed by imputation-based refinement. We have been investigating optimal ways toincrease calling accuracy. To aid us in setting appropriate parameters for VQSR and otherQC steps, we have carried out whole exome sequencing of a small number ofHELIC samples.","abstract":"The HELIC study has been whole genome sequencing individuals from 2 Greek isolatedpopulations at 1x depth. The genotype calling process crucially involves a VQSR stepfollowed by imputation-based refinement. We have been investigating optimal ways toincrease calling accuracy. To aid us in setting appropriate parameters for VQSR and otherQC steps, we have carried out whole exome sequencing of a small number ofHELIC samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-10-16T11:01:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000603","title":"Use_of_Deep_Sequencing_to_Dectect_Clonal_Mutations_In_Sun_Exposed_Skin_Epidermis_PART2","description":"This study aims to define the landscape of somatic mutations in sun exposed human skin by deep sequencing, analyse their frequency and use the data to infer the effect of mutations on proliferating cell behaviour. The frequency of each mutation will reflect the size of the clone of cells in the tissue sample. By analyzing small samples, clones with as few as 100 cells will be detectable. Allele frequency distributions for each mutation will be used to infer cell fate using published methods (Klein et al. 2010). This study will shed unprecedented light on the early clonal events that lead to the emergence of cancer.","abstract":"This study aims to define the landscape of somatic mutations in sun exposed human skin by deep sequencing, analyse their frequency and use the data to infer the effect of mutations on proliferating cell behaviour. The frequency of each mutation will reflect the size of the clone of cells in the tissue sample. By analyzing small samples, clones with as few as 100 cells will be detectable. Allele frequency distributions for each mutation will be used to infer cell fate using published methods (Klein et al. 2010). This study will shed unprecedented light on the early clonal events that lead to the emergence of cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-10-16T11:48:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000604","title":"These are from Korean HCC samples with exome sequencing","description":"Hepatic resection is the most curative treatment option for early-stage hepatocellular carcinoma, but is associated with a high recurrence rate, which exceeds 50% at 5 years after surgery. Understanding the genetic basis of hepatocellular carcinoma at surgically curable stages may enable the identification of new molecular biomarkers that accurately identify patients in need of additional early therapeutic interventions. Whole exome sequencing and copy number analysis was performed on 231 hepatocellular carcinomas (72% with hepatitis B viral infection) that were classified as early-stage hepatocellular carcinomas, candidates for surgical resection. Recurrent mutations were validated by Sanger sequencing. Unsupervised genomic analyses identified an association between specific genetic aberrations and postoperative clinical outcomes. Recurrent somatic mutations were identified in 9 genes, including TP53, CTNNB1, AXIN1, RPS6KA3, and RB1. Recurrent homozygous deletions in FAM123A, RB1, and CDKN2A, and high-copy amplifications in MYC, RSPO2, CCND1, and FGF19 were detected. Pathway analyses of these genes revealed aberrations in the p53, Wnt, PIK3/Ras, cell cycle, and chromatin remodelling pathways. RB1 mutations were significantly associated with cancer-specific and recurrence-free survival after resection (p = 0.016 and p = 0.001, respectively). FGF19 amplifications, known to activate Wnt signalling, were mutually exclusive with CTNNB1 and AXIN1 mutations, and significantly associated with cirrhosis (p = 0.017).  RB1 mutations can be used as a prognostic molecular biomarker for resectable hepatocellular carcinoma. Further study is required to investigate the potential role of FGF19 amplification in driving hepatocarcinogenesis in patients with liver cirrhosis and to investigate the potential of anti-FGF19 treatment in these patients.","abstract":"Hepatic resection is the most curative treatment option for early-stage hepatocellular carcinoma, but is associated with a high recurrence rate, which exceeds 50% at 5 years after surgery. Understanding the genetic basis of hepatocellular carcinoma at surgically curable stages may enable the identification of new molecular biomarkers that accurately identify patients in need of additional early therapeutic interventions. Whole exome sequencing and copy number analysis was performed on 231 hepatocellular carcinomas (72% with hepatitis B viral infection) that were classified as early-stage hepatocellular carcinomas, candidates for surgical resection. Recurrent mutations were validated by Sanger sequencing. Unsupervised genomic analyses identified an association between specific genetic aberrations and postoperative clinical outcomes. Recurrent somatic mutations were identified in 9 genes, including TP53, CTNNB1, AXIN1, RPS6KA3, and RB1. Recurrent homozygous deletions in FAM123A, RB1, and CDKN2A, and high-copy amplifications in MYC, RSPO2, CCND1, and FGF19 were detected. Pathway analyses of these genes revealed aberrations in the p53, Wnt, PIK3/Ras, cell cycle, and chromatin remodelling pathways. RB1 mutations were significantly associated with cancer-specific and recurrence-free survival after resection (p = 0.016 and p = 0.001, respectively). FGF19 amplifications, known to activate Wnt signalling, were mutually exclusive with CTNNB1 and AXIN1 mutations, and significantly associated with cirrhosis (p = 0.017).  RB1 mutations can be used as a prognostic molecular biomarker for resectable hepatocellular carcinoma. Further study is required to investigate the potential role of FGF19 amplification in driving hepatocarcinogenesis in patients with liver cirrhosis and to investigate the potential of anti-FGF19 treatment in these patients.","study_type":"Other","pubmed_ids":[24798001],"external_links":null,"is_released":true,"released_date":"2013-10-17T02:31:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000605","title":"Genome-wide SNP genotyping of Central African rainforest hunter-gatherers and neighbouring agriculturalists","description":"The emergence of agriculture in West-Central Africa, ~5,000 years ago, profoundly modified the cultural landscape and mode of subsistence of most sub-Saharan populations. How this major innovation has impacted the genetic history of rainforest hunter-gatherers — historically referred to as “pygmies” — and agriculturalists, however, remains poorly understood. Here, we report genome-wide SNP data from eight of these populations located west-to-east of the equatorial rainforest. We find that hunter-gathering populations present up to 50% of farmer genomic ancestry, and that substantial admixture began only within the last 1,000 years. Furthermore, we show that the historical population sizes characterising these communities already differed before the introduction of agriculture. Our results suggest that the first socio-economic interactions between rainforest hunter-gatherers and farmers introduced by the spread of farming were not accompanied by immediate, extensive genetic exchanges and occurred on a backdrop of two groups already differentiated by their specialisation in two ecotopes with differing carrying capacities.","abstract":"The emergence of agriculture in West-Central Africa, ~5,000 years ago, profoundly modified the cultural landscape and mode of subsistence of most sub-Saharan populations. How this major innovation has impacted the genetic history of rainforest hunter-gatherers — historically referred to as “pygmies” — and agriculturalists, however, remains poorly understood. Here, we report genome-wide SNP data from eight of these populations located west-to-east of the equatorial rainforest. We find that hunter-gathering populations present up to 50% of farmer genomic ancestry, and that substantial admixture began only within the last 1,000 years. Furthermore, we show that the historical population sizes characterising these communities already differed before the introduction of agriculture. Our results suggest that the first socio-economic interactions between rainforest hunter-gatherers and farmers introduced by the spread of farming were not accompanied by immediate, extensive genetic exchanges and occurred on a backdrop of two groups already differentiated by their specialisation in two ecotopes with differing carrying capacities.","study_type":"Other","pubmed_ids":[24495941],"external_links":null,"is_released":true,"released_date":"2013-10-17T06:56:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000606","title":"Pseudogene_RNAseq","description":"RNA sequencing to validate findings of somatic pseudogenes acquired during cancer development","abstract":"Insertion of processed pseudogenes is known to occur in the germline but has not previously been observed in somatic cells. Formation of pseudogenes could represent a new class of mutation in cancers and a new source of potential driver events","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-10-17T12:27:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000607","title":"SHH medulloblastoma samples","description":"Sequencing data of human SHH medulloblastoma samples","abstract":"Sequencing data of human SHH medulloblastoma samples","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-10-21T14:21:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000608","title":"BLUEPRINT RNA-seq data for haematopoietic progenitor cells, from adult and cord blood samples.","description":"RNA-seq data for haematopoietic progenitor cells, from adult and cord blood samples. Sequenced by the Ouwehand group, University of Cambridge.","abstract":"RNA-seq data for haematopoietic progenitor cells, from adult and cord blood samples. Sequenced by the Ouwehand group, University of Cambridge.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000609","title":"Whole_Genome_Sequencing_of_a_Human_Buccal_Swab_extract","description":"In order to investigate the feasibility of whole genome sequencing a panel of already collected buccal swabs, we intend to process a pilot sample (30ng) from such panel. The outcome of this panel study will inform on the possibility of using buccal swabs, a cheaper and easy to collect source of samples than blood or saliva, to obtain population level whole genome sequencing information. Furthemore, if successful, this pilot will open the possibility of analysing buccal swabs samples collected in the past from remote human populations.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"In order to investigate the feasibility of whole genome sequencing a panel of already collected buccal swabs, we intend to process a pilot sample (30ng) from such panel. The outcome of this panel study will inform on the possibility of using buccal swabs, a cheaper and easy to collect source of samples than blood or saliva, to obtain population level whole genome sequencing information. Furthemore, if successful, this pilot will open the possibility of analysing buccal swabs samples collected in the past from remote human populations.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000610","title":"RNA sequencing and Illumina 2.5M SNP array data collected from 675 commonly used human cancer cell lines.","description":"Tumor-derived cell lines have served as vital models to advance our understanding of oncogene function and therapeutic response1. Although substantial effort has been directed to defining the genomic constitution of cancer cell line panels2–4, the transcriptome – which represents the active program of a cell – remains understudied. Here, we describe RNA sequencing and SNP array analysis of 675 commonly used human cancer cell lines. We explore numerous transcriptome features including coding and non-coding gene expression, transcribed mutations, gene fusion and expression of non-human sequences. Aside from many known aberrations we find new surprising characteristics, including more than 2200 unique fusion gene pairs representing a vast, testable repertoire of oncogenic fusions, many of which have analogs found in primary human tumors. We show that a combination of multiple genome and transcriptome features in a novel pathway-based approach enhances prediction of response to various targeted therapeutics. Our results provide valuable new insights into these critical pre-clinical models and provide added context for interpreting the numerous studies that employ these widely used cell lines.","abstract":"Tumor-derived cell lines have served as vital models to advance our understanding of oncogene function and therapeutic response1. Although substantial effort has been directed to defining the genomic constitution of cancer cell line panels2–4, the transcriptome – which represents the active program of a cell – remains understudied. Here, we describe RNA sequencing and SNP array analysis of 675 commonly used human cancer cell lines. We explore numerous transcriptome features including coding and non-coding gene expression, transcribed mutations, gene fusion and expression of non-human sequences. Aside from many known aberrations we find new surprising characteristics, including more than 2200 unique fusion gene pairs representing a vast, testable repertoire of oncogenic fusions, many of which have analogs found in primary human tumors. We show that a combination of multiple genome and transcriptome features in a novel pathway-based approach enhances prediction of response to various targeted therapeutics. Our results provide valuable new insights into these critical pre-clinical models and provide added context for interpreting the numerous studies that employ these widely used cell lines.","study_type":"Other","pubmed_ids":[25485619],"external_links":null,"is_released":true,"released_date":"2013-10-22T21:55:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000611","title":"HKU Gastric Cancer Genomics study - whole genome sequencing, DNA genotyping array, expression profiling and methylation profiling","description":"pending","abstract":"pending","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000612","title":"PLCRC_study","description":"Genomic libraries (500 bps) will be generated from total genomic DNA derived from Colorectal cancer patients and subjected to short paired end sequencing on the llumina platform. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemias, lymphomas and soft tissue tumors. However, conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution. We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-10-24T14:57:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000613","title":"Mosaic_Colorectal_Metastasis","description":"A comparison of the somatic variation present in a primary colorectal tumour and three different liver metastases from the same patient.","abstract":"A comparison of the somatic variation present in a primary colorectal tumour and three different liver metastases from the same patient.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-10-24T15:39:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000614","title":"PMCPL_Exome_Study","description":"To compare clonal composition of primary breast tumours with multiple metastases, interrogate heterogeneity  of CTC’s to identify subclones responsible for metastatic disease and to identify druggable targets.","abstract":"To compare clonal composition of primary breast tumours with multiple metastases, interrogate heterogeneity  of CTC’s to identify subclones responsible for metastatic disease and to identify druggable targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000615","title":"Osteosarcoma_RNAseq","description":"We propose to definitively characterise the somatic genetics of Osteosarcoma cancer through generation of comprehensive catalogues of somatic mutations by high coverage genome and transcriptome sequencing.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-10-24T15:58:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000616","title":"BIG_MS_Pilot","description":"Testing logistics and infrastructure of molecular screening program. Core biopsies taken from invasive recurrent or metastatic breast cancer to evaluate and identify molecular traits rendering them suitable for clinical trials","abstract":"Testing logistics and infrastructure of molecular screening program. Core biopsies taken from invasive recurrent or metastatic breast cancer to evaluate and identify molecular traits rendering them suitable for clinical trials","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-10-24T16:08:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000617","title":"Identification_of_drug_resistance_genes_in_melanoma","description":"Our aim is to analyze the genome of human melanoma cell lines and short term culture from human melanoma samples in order to identify genes that confer drug resistance to clinically relevant targeted therapies. We will perform whole-exome sequencing, copy number variation analysis and methylome analysis in a collection of human melanoma cell lines and short term culture that will be then screened  for drug sensitivity/resistance through a library of clinically relevant drugs and drug combinations. By the combined analysis of the genomic lesion and the drug sensitivity/resistance profile of different cell lines, we will look for genes whose mutation is associated to the sensitivity or resistance to a specific drug in different samples.","abstract":"Malignant melanoma is a highly aggressive form of skin cancer with a poor outcome following metastatic spread. Despite providing significant rates of response, the newly developed  targeted therapies (such as BRAF inhibitors) rarely result in disease eradication due to the emergence of drug-resistant clones that provoke tumor relapse.The likelihood of response of each melanoma to treatment with specific drugs is strongly influenced by the mutational landscape of its genome. The identification of genes and molecular pathways whose deregulation is causative of unresponsiveness to therapy is urgently required for a better stratification of patients towards more effective personalized treatments and to design combinations of existing and novel drugs capable to overcome the development of resistance. In order to study the molecular mechanism that drive melanoma drug resistance, we will analyze the genome of human melanoma samples. By comparing the mutational landscape of our melanoma collection with the drug sensitivity/resistance profiles of the cell lines/short-term cultures we hope to identify new melanoma drug resistance genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-10-28T14:50:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000618","title":"Massive genome sequencing of random people","description":"Circulating biomarkers such as somatic chromosome mutations are novel diagnostic tools to detect cancer noninvasively. We describe focal deletions found in a patient with atypical teratoid rhabdoid tumor, a highly aggressive early childhood pediatric tumor. First, we used magnetic resonance imaging (MRI) and histopathology to study the tumor anatomy. Next, we used whole genome sequencing (Next Gen Sequencing) and Bioinformatics interrogation to discover the presence of 3 focal deletions in tumor tissue and 2 of these 3 focal deletions in patient's blood also. About 20% of the blood DNA sequencing reads matched the tumor DNA reads at the SMARCB1 gene locus. Circulating, tumor-specific DNA aberrations are a promising biomarker for atypical teratoid rhabdoid tumor patients. The high percentage of tumor DNA detected in blood indicates that either circulating brain tumor cells lyse in the blood or that contents of brain tumor cells traverse a possibly compromised blood-brain barrier in this patient.","abstract":"Circulating biomarkers such as somatic chromosome mutations are novel diagnostic tools to detect cancer noninvasively. We describe focal deletions found in a patient with atypical teratoid rhabdoid tumor, a highly aggressive early childhood pediatric tumor. First, we used magnetic resonance imaging (MRI) and histopathology to study the tumor anatomy. Next, we used whole genome sequencing (Next Gen Sequencing) and Bioinformatics interrogation to discover the presence of 3 focal deletions in tumor tissue and 2 of these 3 focal deletions in patient's blood also. About 20% of the blood DNA sequencing reads matched the tumor DNA reads at the SMARCB1 gene locus. Circulating, tumor-specific DNA aberrations are a promising biomarker for atypical teratoid rhabdoid tumor patients. The high percentage of tumor DNA detected in blood indicates that either circulating brain tumor cells lyse in the blood or that contents of brain tumor cells traverse a possibly compromised blood-brain barrier in this patient.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000619","title":"Acquisition_of_additional_mutations_drives_accelerated_progression_of_NPM1_positive_CMML_to_AML_","description":"This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/We performed exome sequencing on serial samples from a patient with CMML who progressed to AML.  The exome sequencing suggests that NPM1, TET2 and DNMT3a mutations were present in the dominant clone in the CMML sample and that NRAS is a new subclonal mutation in the AML sample. Diagnostic data shows the presence of a FLT3-ITD mutation in the AML sample, which is likely to have driven progression.  Here we are performing re-sequencing of the putative driver and some passenger mutations which appear to be in the same clone to validate these mutations and to verify the relative quantification of these abnormalities .","abstract":"We performed exome sequencing on serial samples from a patient with CMML who progressed to AML.  The exome sequencing suggests that NPM1, TET2 and DNMT3a mutations were present in the dominant clone in the CMML sample and that NRAS is a new subclonal mutation in the AML sample. Diagnostic data shows the presence of a FLT3-ITD mutation in the AML sample, which is likely to have driven progression.  Here we are performing re-sequencing of the putative driver and some passenger mutations which appear to be in the same clone to validate these mutations and to verify the relative quantification of these abnormalities .","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-10-31T10:33:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000620","title":"Identification_of_rare_variants_associated_with_cardiovascular_traits_in_Cilento_isolates","description":"The aim of this project is to identify rare genetic variants of large effect implicated in complex diseases by focusing on the study of cardiovascular diseases and related quantitative traits in a well characterized isolated population in Cilento area, Italy.The reference panel has been selected carefully in order to maximize the imputation coverage and quality on the all population samples. The selected individuals should meet three criteria: selected individuals should be chip-genotyped and closely related to the maximum number of chip-genotyped individuals so as to maximize imputation coverage; relatedness between selected individuals should be minimal, so as to minimize redundancy in genetic information of the reference panel.We perform exome sequencing on samples from 250 individuals from the Campora and Gioi-Cardile populations.","abstract":"The aim of this project is to identify rare genetic variants of large effect implicated in complex diseases by focusing on the study of cardiovascular diseases and related quantitative traits in a well characterized isolated population in Cilento area, Italy.The reference panel has been selected carefully in order to maximize the imputation coverage and quality on the all population samples. The selected individuals should meet three criteria: selected individuals should be chip-genotyped and closely related to the maximum number of chip-genotyped individuals so as to maximize imputation coverage; relatedness between selected individuals should be minimal, so as to minimize redundancy in genetic information of the reference panel.We perform exome sequencing on samples from 250 individuals from the Campora and Gioi-Cardile populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-10-31T15:02:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000621","title":"Whole Genome Sequencing of Asian Lung Cancers: Second Hand Smoke is Not Responsible for Higher Incidence of Lung Cancer Among Asian Never-Smokers","description":"Background Asian nonsmoking populations have a higher incidence of lung cancer compared to their European counterparts. There is a long-standing hypothesis that the increase of lung cancer in Asian never-smokers is due to environmental factors such as second-hand smoke. Results We analyzed whole-genome sequencing of 30 Asian lung cancers. Unsupervised clustering of mutational signatures separated the patients into two categories: i) all of the never-smokers, and ii) only smokers or ex-smokers. Half of the ex-smokers / smokers were in the never-smoker-like cluster. The overall somatic variant profiles of Asian lung cancers were similar to that of European origin with G.C&gt;T.A being predominant in smokers. We found EGFR and TP53 are the most frequently mutated genes with mutations in 50% and 27% of individuals, respectively. Among these Asian never-smokers, 71% had an EGFR mutation compared to 20% of the smokers in the smoking cluster. Other frequently mutated genes include RYR2, SATB2, C1orf88, FERMT1 and CTNNB1. Somatic alterations occurred in WNT signaling pathway genes, suggesting this pathway plays a role in both Western and Asian lung cancers. Conclusions Asian never-smokers have lung cancer signatures distinct from the smoker signature and their mutation profiles are similar to that of European never-smokers. The profiles of Asian and European smokers are also similar. This suggests that the same mutational mechanisms underlie the etiology for both ethnic groups, and the high incidence of lung cancer in Asian never-smokers might not be due to second hand smoke or other carcinogens that cause oxidative DNA damage. Half of the ex-smokers/smokers have a molecular phenotype similar to never-smokers; of which, 50% had EGFR mutations.  This suggests that routine EGFR testing is warranted in the Asian population, regardless of smoking status.","abstract":"Background Asian nonsmoking populations have a higher incidence of lung cancer compared to their European counterparts. There is a long-standing hypothesis that the increase of lung cancer in Asian never-smokers is due to environmental factors such as second-hand smoke. Results We analyzed whole-genome sequencing of 30 Asian lung cancers. Unsupervised clustering of mutational signatures separated the patients into two categories: i) all of the never-smokers, and ii) only smokers or ex-smokers. Half of the ex-smokers / smokers were in the never-smoker-like cluster. The overall somatic variant profiles of Asian lung cancers were similar to that of European origin with G.C&gt;T.A being predominant in smokers. We found EGFR and TP53 are the most frequently mutated genes with mutations in 50% and 27% of individuals, respectively. Among these Asian never-smokers, 71% had an EGFR mutation compared to 20% of the smokers in the smoking cluster. Other frequently mutated genes include RYR2, SATB2, C1orf88, FERMT1 and CTNNB1. Somatic alterations occurred in WNT signaling pathway genes, suggesting this pathway plays a role in both Western and Asian lung cancers. Conclusions Asian never-smokers have lung cancer signatures distinct from the smoker signature and their mutation profiles are similar to that of European never-smokers. The profiles of Asian and European smokers are also similar. This suggests that the same mutational mechanisms underlie the etiology for both ethnic groups, and the high incidence of lung cancer in Asian never-smokers might not be due to second hand smoke or other carcinogens that cause oxidative DNA damage. Half of the ex-smokers/smokers have a molecular phenotype similar to never-smokers; of which, 50% had EGFR mutations.  This suggests that routine EGFR testing is warranted in the Asian population, regardless of smoking status.","study_type":"Other","pubmed_ids":[25189529],"external_links":null,"is_released":true,"released_date":"2013-11-01T06:00:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000622","title":"Pharmacological and genomic profiling identifies NFκB-targeted treatment strategies for mantle cell lymphoma","description":"Mantle cell lymphoma (MCL) is an aggressive malignancy characterized by poor prognosis, underscoring the need for novel therapeutic strategies1. In this study, we employed large-scale pharmacological profiling of 16 pathway inhibitors across more than 100 hematological cell line models to identify novel therapeutic approaches. This screen identified a subset of MCL cell lines that were highly sensitive to the B-cell receptor (BCR) signaling inhibitors ibrutinib and sotrastaurin (STN), which are currently in clinical trials2, 3. Sensitive MCL models exhibited chronic activation of the CARD11-BCL10-MALT1 (CBM) complex and dependency on downstream classical NFκB signaling. In contrast, insensitive cell lines displayed activation of the alternative NFκB pathway. Massively parallel transcriptome sequencing identified mutations in negative regulators of the alternative NFκB pathway in ibrutinib-insensitive cell lines. Notably, sequencing of 165 MCL patient samples  revealed that components of the alternative NFκB pathway, particularly TRAF2 and BIRC3, are mutated in roughly 15% of MCL patients. Functional analyses of patient-derived BIRC3 mutant alleles indicated that these are loss-of-function mutants that constitutively activate alternative NFκB signaling. While being associated with insensitivity to ibrutinib, genetic lesions in the alternative pathway conferred dependence on NIK, a kinase that mediates signaling downstream of the TRAF2/3-BIRC2/3 complex. Thus, NIK represents a novel therapeutic target for MCL treatment, particularly for tumors refractory to BCR pathway inhibitors. Collectively, these findings reveal a pattern of mutually exclusive activation of the CBM-NFκB or alternative NIK-NFκB pathways in MCL and provide critical insights into patient stratification strategies for NFκB-pathway targeted agents.","abstract":"Mantle cell lymphoma (MCL) is an aggressive malignancy characterized by poor prognosis, underscoring the need for novel therapeutic strategies1. In this study, we employed large-scale pharmacological profiling of 16 pathway inhibitors across more than 100 hematological cell line models to identify novel therapeutic approaches. This screen identified a subset of MCL cell lines that were highly sensitive to the B-cell receptor (BCR) signaling inhibitors ibrutinib and sotrastaurin (STN), which are currently in clinical trials2, 3. Sensitive MCL models exhibited chronic activation of the CARD11-BCL10-MALT1 (CBM) complex and dependency on downstream classical NFκB signaling. In contrast, insensitive cell lines displayed activation of the alternative NFκB pathway. Massively parallel transcriptome sequencing identified mutations in negative regulators of the alternative NFκB pathway in ibrutinib-insensitive cell lines. Notably, sequencing of 165 MCL patient samples  revealed that components of the alternative NFκB pathway, particularly TRAF2 and BIRC3, are mutated in roughly 15% of MCL patients. Functional analyses of patient-derived BIRC3 mutant alleles indicated that these are loss-of-function mutants that constitutively activate alternative NFκB signaling. While being associated with insensitivity to ibrutinib, genetic lesions in the alternative pathway conferred dependence on NIK, a kinase that mediates signaling downstream of the TRAF2/3-BIRC2/3 complex. Thus, NIK represents a novel therapeutic target for MCL treatment, particularly for tumors refractory to BCR pathway inhibitors. Collectively, these findings reveal a pattern of mutually exclusive activation of the CBM-NFκB or alternative NIK-NFκB pathways in MCL and provide critical insights into patient stratification strategies for NFκB-pathway targeted agents.","study_type":"Other","pubmed_ids":[24362935],"external_links":null,"is_released":true,"released_date":"2013-11-05T00:01:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000623","title":"Maternal Plasma Fetal DNA Fractions in Pregnancies with Low and High Risks for Fetal Chromosomal Aneuploidies","description":"Maternal Plasma Fetal DNA Fractions in Pregnancies with Low and High Risks for Fetal Chromosomal Aneuploidies","abstract":"Maternal Plasma Fetal DNA Fractions in Pregnancies with Low and High Risks for Fetal Chromosomal Aneuploidies","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000624","title":"WTCCC2 project Glaucoma (GL) samples","description":"A WTCCC2 genome-wide association study for glaucoma (GL) in Australian individuals of European descent.","abstract":"A WTCCC2 genome-wide association study for glaucoma (GL) in Australian individuals of European descent.","study_type":"Other","pubmed_ids":[23836780],"external_links":null,"is_released":true,"released_date":"2013-11-06T17:33:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000625","title":"Divergence between high metastatic tumor burden and  low circulating tumor DNA concentration in metastasized breast cancer","description":"Circulating tumor DNA (ctDNA) was reported to represent a highly sensitive biomarker of metastatic cancer disease directly reflecting tumor burden and dynamics. Here we investigated the role of ctDNA in patients with metastatic breast cancer. In an index patient with more than 100,000 circulating tumor cells (CTCs) in serial blood analyses, whole genome, exome, or targeted deep sequencing of the primary tumor, metastases, and 551 CTCs were consistent with a genetically homogeneous cancer. However, the allele fractions (AFs) of ctDNA were only 2-3% in each analysis, which did neither reflect the tumor burden nor the dynamics of this progressive disease by far. Indeed, plasma analyses of 71 further patients demonstrated highly variable AFs of mutant fragments, which frequently did not correspond to the tumor burden. These results provide insights into mechanisms involved in CTC and ctDNA release into the circulation and have important implications for diagnostic tests based on liquid biopsies.","abstract":"Circulating tumor DNA (ctDNA) was reported to represent a highly sensitive biomarker of metastatic cancer disease directly reflecting tumor burden and dynamics. Here we investigated the role of ctDNA in patients with metastatic breast cancer. In an index patient with more than 100,000 circulating tumor cells (CTCs) in serial blood analyses, whole genome, exome, or targeted deep sequencing of the primary tumor, metastases, and 551 CTCs were consistent with a genetically homogeneous cancer. However, the allele fractions (AFs) of ctDNA were only 2-3% in each analysis, which did neither reflect the tumor burden nor the dynamics of this progressive disease by far. Indeed, plasma analyses of 71 further patients demonstrated highly variable AFs of mutant fragments, which frequently did not correspond to the tumor burden. These results provide insights into mechanisms involved in CTC and ctDNA release into the circulation and have important implications for diagnostic tests based on liquid biopsies.","study_type":"Other","pubmed_ids":[25107527],"external_links":null,"is_released":true,"released_date":"2013-11-12T07:50:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000626","title":"Haemoglobin_E_beta_thalassaemia_in_a_patient_group_from_Sri_Lanka","description":"Exome sequencing of 32 patient samples from Sri Lanka with the condition haemoglobin E beta thalassaemia","abstract":"Haemoglobin E beta thalassaemia affects thousands of children in south and southeast Asia and is by far the most common form of severe thalassaemia in this region. Compared with other severe forms of beta thalassaemia this condition shows quite remarkable clinical heterogeneity and by following a group of patients in Sri Lanka it has been possible to define several genetic modifiers using the candidate gene approach. The proposal is to exome sequence 32 of these patient samples, half of the 32 samples are from mild phenotypes and half are from extremely severe phenotypes and it is hoped to define further genetic polymorphisms that may underlie the remarkable clinical variability of this condition, a finding that would be of considerable importance in their future management. This project is a collaboration with Professor Sir David Weatherall of the Weatherall Institute of Molecular Medicine. Funded by the Wellcome Trust.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-11-12T13:16:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000627","title":"Leiden_melanomafamilies","description":"Around 10% of patients who present in melanoma clinics have a first degree relative with a previous diagnosis of melanoma. While around 3% have three or more relatives who have been diagnosed with the disease. In this project we will whole genome sequence patients from large Dutch familial melanoma pedigrees to identify mutations in genes that drive melanomagenesis. The identification of these genes will facilitate the management of familial melanoma patients and their families.","abstract":"Around 10% of patients who present in melanoma clinics have a first degree relative with a previous diagnosis of melanoma. While around 3% have three or more relatives who have been diagnosed with the disease. In this project we will whole genome sequence patients from large Dutch familial melanoma pedigrees to identify mutations in genes that drive melanomagenesis. The identification of these genes will facilitate the management of familial melanoma patients and their families.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-11-13T14:12:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000628","title":"WTCCC2 BO (Barretts oesophagus) samples","description":"A WTCCC2 project genome-wide case-control association study for Barretts oesophagus in individuals from the UK.","abstract":"A WTCCC2 project genome-wide case-control association study for Barretts oesophagus in individuals from the UK.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-11-15T12:38:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000629","title":"WGS_low_coverage_sequencing_of_Fulani_from_Burkina_Faso","description":"We aim to provide a powerful reference set for genome-wide association studies (GWAS) in African populations. Our pilot study to sequence 100 individuals each from Fula, Jola, Mandinka and Wollof from the Gambia to low coverage has been completed - this first part of the main effort will make available low coverage WGS data for 400 individuals from multiple ethnic groups in Burkina Faso, Cameroon, Ghana and Tanzania. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This project forms a central part of the Genomic Epidemiology of Malaria Project within the Sanger Quinquennial Plan. It uses DNA samples and clinical data that have been collected as part of an ongoing multi-centre study of severe malaria undertaken by MalariaGEN, coordinated jointly by the Sanger Institute and Oxford University.We have previously genotyped &gt;23,000 individuals from 11 countries using Illumina 2.5M SNP array. Although this array is much denser than previous generations of genotyping arrays, it is still too sparse to cover genetic variability in malaria-endemic populations. To get a denser marker map for a genome-wide association study (GWAS), we need to impute genotypes based on sequencing data. There are some publicly available reference sets for imputation provided by HapMap and the 1000 Genomes project. Unfortunately, African populations are under-represented in the available reference sets and most of the populations we have genotyped have no publicly available sequence data.We have previously tested the usefulness of Nigerian sequence data for imputation of genotypes in a Gambian GWAS around a known malaria resistance locus (HBB) - unfortunately the association signal was lost through imputation because these two populations have different haplotypic backgrounds in this locus. This is just one example of the level of genetic variability we have encountered in African populations, and underlines the fact that to impute genotypes successfully, we need to sequence individuals from the countries - and the ethnic groups within each country - that are represented in our GWAS.We have completed sequencing of 100 individuals each from four ethnic groups in the Gambia (Fula, Jola, Mandinka and Wollof), and the currect project will expand sequencing to other populations that are represented in our multi-centre GWAS of severe malaria. It will cover 1-2 ethnic groups each from Burkina Faso, Cameroon, Ghana and Tanzania to a total of400 individuals.The primary motive of this project is to maximise our power to detect association to malaria resistance/susceptibility but these data will also provide an information repository on genome variation and GWAS assay design in African populations, and will be highly complementary to other Sanger work in this area.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000630","title":"Illumina ExomeChip genotyping data from the Cretan Greek isolate collection HELIC MANOLIS","description":"Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies. Here we have genotyped individuals from a Greek population isolate on the Illumina HumanExome Beadchip. The HELIC (Hellenic Isolated Cohorts) MANOLIS (Minoan Isolates) collection focuses on Anogia and surrounding Mylopotamos villages. Recruitment of this population-based sample was primarily carried out at the village medical centres. All individuals were older than 17 years and had to have at least one parent from the Mylopotamos area. www.helic.org  **The data may not be used for population genetics analyses.**","abstract":"Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies. Here we have genotyped individuals from a Greek population isolate on the Illumina HumanExome Beadchip. The HELIC (Hellenic Isolated Cohorts) MANOLIS (Minoan Isolates) collection focuses on Anogia and surrounding Mylopotamos villages. Recruitment of this population-based sample was primarily carried out at the village medical centres. All individuals were older than 17 years and had to have at least one parent from the Mylopotamos area. www.helic.org  **The data may not be used for population genetics analyses.**","study_type":"Other","pubmed_ids":[24343240],"external_links":null,"is_released":true,"released_date":"2013-11-22T16:50:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000631","title":"WGS_low_coverage_sequencing_of_Mossi_from_Burkina_Faso","description":"We aim to provide a powerful reference set for genome-wide association studies (GWAS) in African populations. Our pilot study to sequence 100 individuals each from Fula, Jola, Mandinka and Wollof from the Gambia to low coverage has been completed - this first part of the main effort will make available low coverage WGS data for 400 individuals from multiple ethnic groups in Burkina Faso, Cameroon, Ghana and Tanzania. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This project forms a central part of the Genomic Epidemiology of Malaria Project within the Sanger Quinquennial Plan. It uses DNA samples and clinical data that have been collected as part of an ongoing multi-centre study of severe malaria undertaken by MalariaGEN, coordinated jointly by the Sanger Institute and Oxford University.We have previously genotyped &gt;23,000 individuals from 11 countries using Illumina 2.5M SNP array. Although this array is much denser than previous generations of genotyping arrays, it is still too sparse to cover genetic variability in malaria-endemic populations. To get a denser marker map for a genome-wide association study (GWAS), we need to impute genotypes based on sequencing data. There are some publicly available reference sets for imputation provided by HapMap and the 1000 Genomes project. Unfortunately, African populations are under-represented in the available reference sets and most of the populations we have genotyped have no publicly available sequence data.We have previously tested the usefulness of Nigerian sequence data for imputation of genotypes in a Gambian GWAS around a known malaria resistance locus (HBB) - unfortunately the association signal was lost through imputation because these two populations have different haplotypic backgrounds in this locus. This is just one example of the level of genetic variability we have encountered in African populations, and underlines the fact that to impute genotypes successfully, we need to sequence individuals from the countries ? and the ethnic groups within each country ? that are represented in our GWAS.We have completed sequencing of 100 individuals each from four ethnic groups in the Gambia (Fula, Jola, Mandinka and Wollof), and the currect project will expand sequencing to other populations that are represented in our multi-centre GWAS of severe malaria. It will cover 1-2 ethnic groups each from Burkina Faso, Cameroon, Ghana and Tanzania to a total of400 individuals.The primary motive of this project is to maximise our power to detect association to malaria resistance/susceptibility but these data will also provide an information repository on genome variation and GWAS assay design in African populations, and will be highly complementary to other Sanger work in this area.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000632","title":"WGS_low_coverage_sequencing_of_Bantu_from_Cameroon","description":"We aim to provide a powerful reference set for genome-wide association studies (GWAS) in African populations. Our pilot study to sequence 100 individuals each from Fula, Jola, Mandinka and Wollof from the Gambia to low coverage has been completed - this first part of the main effort will make available low coverage WGS data for 400 individuals from multiple ethnic groups in Burkina Faso, Cameroon, Ghana and Tanzania. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This project forms a central part of the Genomic Epidemiology of Malaria Project within the Sanger Quinquennial Plan. It uses DNA samples and clinical data that have been collected as part of an ongoing multi-centre study of severe malaria undertaken by MalariaGEN, coordinated jointly by the Sanger Institute and Oxford University.We have previously genotyped &gt;23,000 individuals from 11 countries using Illumina 2.5M SNP array. Although this array is much denser than previous generations of genotyping arrays, it is still too sparse to cover genetic variability in malaria-endemic populations. To get a denser marker map for a genome-wide association study (GWAS), we need to impute genotypes based on sequencing data. There are some publicly available reference sets for imputation provided by HapMap and the 1000 Genomes project. Unfortunately, African populations are under-represented in the available reference sets and most of the populations we have genotyped have no publicly available sequence data.We have previously tested the usefulness of Nigerian sequence data for imputation of genotypes in a Gambian GWAS around a known malaria resistance locus (HBB) - unfortunately the association signal was lost through imputation because these two populations have different haplotypic backgrounds in this locus. This is just one example of the level of genetic variability we have encountered in African populations, and underlines the fact that to impute genotypes successfully, we need to sequence individuals from the countries - and the ethnic groups within each country - that are represented in our GWAS.We have completed sequencing of 100 individuals each from four ethnic groups in the Gambia (Fula, Jola, Mandinka and Wollof), and the currect project will expand sequencing to other populations that are represented in our multi-centre GWAS of severe malaria. It will cover 1-2 ethnic groups each from Burkina Faso, Cameroon, Ghana and Tanzania to a total of400 individuals.The primary motive of this project is to maximise our power to detect association to malaria resistance/susceptibility but these data will also provide an information repository on genome variation and GWAS assay design in African populations, and will be highly complementary to other Sanger work in this area.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000633","title":"WGS_low_coverage_sequencing_of_Semi_Bantu_from_Cameroon","description":"We aim to provide a powerful reference set for genome-wide association studies (GWAS) in African populations. Our pilot study to sequence 100 individuals each from Fula, Jola, Mandinka and Wollof from the Gambia to low coverage has been completed - this first part of the main effort will make available low coverage WGS data for 400 individuals from multiple ethnic groups in Burkina Faso, Cameroon, Ghana and Tanzania. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This project forms a central part of the Genomic Epidemiology of Malaria Project within the Sanger Quinquennial Plan. It uses DNA samples and clinical data that have been collected as part of an ongoing multi-centre study of severe malaria undertaken by MalariaGEN, coordinated jointly by the Sanger Institute and Oxford University.We have previously genotyped &gt;23,000 individuals from 11 countries using Illumina 2.5M SNP array. Although this array is much denser than previous generations of genotyping arrays, it is still too sparse to cover genetic variability in malaria-endemic populations. To get a denser marker map for a genome-wide association study (GWAS), we need to impute genotypes based on sequencing data. There are some publicly available reference sets for imputation provided by HapMap and the 1000 Genomes project. Unfortunately, African populations are under-represented in the available reference sets and most of the populations we have genotyped have no publicly available sequence data.We have previously tested the usefulness of Nigerian sequence data for imputation of genotypes in a Gambian GWAS around a known malaria resistance locus (HBB) - unfortunately the association signal was lost through imputation because these two populations have different haplotypic backgrounds in this locus. This is just one example of the level of genetic variability we have encountered in African populations, and underlines the fact that to impute genotypes successfully, we need to sequence individuals from the countries – and the ethnic groups within each country – that are represented in our GWAS.We have completed sequencing of 100 individuals each from four ethnic groups in the Gambia (Fula, Jola, Mandinka and Wollof), and the currect project will expand sequencing to other populations that are represented in our multi-centre GWAS of severe malaria. It will cover 1-2 ethnic groups each from Burkina Faso, Cameroon, Ghana and Tanzania to a total of400 individuals.The primary motive of this project is to maximise our power to detect association to malaria resistance/susceptibility but these data will also provide an information repository on genome variation and GWAS assay design in African populations, and will be highly complementary to other Sanger work in this area.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000634","title":"WGS_low_coverage_sequencing_of_Kassem_from_Ghana","description":"We aim to provide a powerful reference set for genome-wide association studies (GWAS) in African populations. Our pilot study to sequence 100 individuals each from Fula, Jola, Mandinka and Wollof from the Gambia to low coverage has been completed - this first part of the main effort will make available low coverage WGS data for 400 individuals from multiple ethnic groups in Burkina Faso, Cameroon, Ghana and Tanzania. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This project forms a central part of the Genomic Epidemiology of Malaria Project within the Sanger Quinquennial Plan. It uses DNA samples and clinical data that have been collected as part of an ongoing multi-centre study of severe malaria undertaken by MalariaGEN, coordinated jointly by the Sanger Institute and Oxford University.We have previously genotyped &gt;23,000 individuals from 11 countries using Illumina 2.5M SNP array. Although this array is much denser than previous generations of genotyping arrays, it is still too sparse to cover genetic variability in malaria-endemic populations. To get a denser marker map for a genome-wide association study (GWAS), we need to impute genotypes based on sequencing data. There are some publicly available reference sets for imputation provided by HapMap and the 1000 Genomes project. Unfortunately, African populations are under-represented in the available reference sets and most of the populations we have genotyped have no publicly available sequence data.We have previously tested the usefulness of Nigerian sequence data for imputation of genotypes in a Gambian GWAS around a known malaria resistance locus (HBB) - unfortunately the association signal was lost through imputation because these two populations have different haplotypic backgrounds in this locus. This is just one example of the level of genetic variability we have encountered in African populations, and underlines the fact that to impute genotypes successfully, we need to sequence individuals from the countries - and the ethnic groups within each country - that are represented in our GWAS.We have completed sequencing of 100 individuals each from four ethnic groups in the Gambia (Fula, Jola, Mandinka and Wollof), and the currect project will expand sequencing to other populations that are represented in our multi-centre GWAS of severe malaria. It will cover 1-2 ethnic groups each from Burkina Faso, Cameroon, Ghana and Tanzania to a total of400 individuals.The primary motive of this project is to maximise our power to detect association to malaria resistance/susceptibility but these data will also provide an information repository on genome variation and GWAS assay design in African populations, and will be highly complementary to other Sanger work in this area.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000635","title":"WGS_low_coverage_sequencing_of_Nankam_from_Ghana","description":"We aim to provide a powerful reference set for genome-wide association studies (GWAS) in African populations. Our pilot study to sequence 100 individuals each from Fula, Jola, Mandinka and Wollof from the Gambia to low coverage has been completed - this first part of the main effort will make available low coverage WGS data for 400 individuals from multiple ethnic groups in Burkina Faso, Cameroon, Ghana and Tanzania. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This project forms a central part of the Genomic Epidemiology of Malaria Project within the Sanger Quinquennial Plan. It uses DNA samples and clinical data that have been collected as part of an ongoing multi-centre study of severe malaria undertaken by MalariaGEN, coordinated jointly by the Sanger Institute and Oxford University.We have previously genotyped &gt;23,000 individuals from 11 countries using Illumina 2.5M SNP array. Although this array is much denser than previous generations of genotyping arrays, it is still too sparse to cover genetic variability in malaria-endemic populations. To get a denser marker map for a genome-wide association study (GWAS), we need to impute genotypes based on sequencing data. There are some publicly available reference sets for imputation provided by HapMap and the 1000 Genomes project. Unfortunately, African populations are under-represented in the available reference sets and most of the populations we have genotyped have no publicly available sequence data.We have previously tested the usefulness of Nigerian sequence data for imputation of genotypes in a Gambian GWAS around a known malaria resistance locus (HBB) - unfortunately the association signal was lost through imputation because these two populations have different haplotypic backgrounds in this locus. This is just one example of the level of genetic variability we have encountered in African populations, and underlines the fact that to impute genotypes successfully, we need to sequence individuals from the countries - and the ethnic groups within each country - that are represented in our GWAS.We have completed sequencing of 100 individuals each from four ethnic groups in the Gambia (Fula, Jola, Mandinka and Wollof), and the currect project will expand sequencing to other populations that are represented in our multi-centre GWAS of severe malaria. It will cover 1-2 ethnic groups each from Burkina Faso, Cameroon, Ghana and Tanzania to a total of400 individuals.The primary motive of this project is to maximise our power to detect association to malaria resistance/susceptibility but these data will also provide an information repository on genome variation and GWAS assay design in African populations, and will be highly complementary to other Sanger work in this area.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000636","title":"WGS_low_coverage_sequencing_of_Chagga_from_Tanzania","description":"We aim to provide a powerful reference set for genome-wide association studies (GWAS) in African populations. Our pilot study to sequence 100 individuals each from Fula, Jola, Mandinka and Wollof from the Gambia to low coverage has been completed - this first part of the main effort will make available low coverage WGS data for 400 individuals from multiple ethnic groups in Burkina Faso, Cameroon, Ghana and Tanzania. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This project forms a central part of the Genomic Epidemiology of Malaria Project within the Sanger Quinquennial Plan. It uses DNA samples and clinical data that have been collected as part of an ongoing multi-centre study of severe malaria undertaken by MalariaGEN, coordinated jointly by the Sanger Institute and Oxford University.We have previously genotyped &gt;23,000 individuals from 11 countries using Illumina 2.5M SNP array. Although this array is much denser than previous generations of genotyping arrays, it is still too sparse to cover genetic variability in malaria-endemic populations. To get a denser marker map for a genome-wide association study (GWAS), we need to impute genotypes based on sequencing data. There are some publicly available reference sets for imputation provided by HapMap and the 1000 Genomes project. Unfortunately, African populations are under-represented in the available reference sets and most of the populations we have genotyped have no publicly available sequence data.We have previously tested the usefulness of Nigerian sequence data for imputation of genotypes in a Gambian GWAS around a known malaria resistance locus (HBB) - unfortunately the association signal was lost through imputation because these two populations have different haplotypic backgrounds in this locus. This is just one example of the level of genetic variability we have encountered in African populations, and underlines the fact that to impute genotypes successfully, we need to sequence individuals from the countries – and the ethnic groups within each country – that are represented in our GWAS.We have completed sequencing of 100 individuals each from four ethnic groups in the Gambia (Fula, Jola, Mandinka and Wollof), and the currect project will expand sequencing to other populations that are represented in our multi-centre GWAS of severe malaria. It will cover 1-2 ethnic groups each from Burkina Faso, Cameroon, Ghana and Tanzania to a total of400 individuals.The primary motive of this project is to maximise our power to detect association to malaria resistance/susceptibility but these data will also provide an information repository on genome variation and GWAS assay design in African populations, and will be highly complementary to other Sanger work in this area.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000637","title":"WGS_low_coverage_sequencing_of_Pare_from_Tanzania","description":"We aim to provide a powerful reference set for genome-wide association studies (GWAS) in African populations. Our pilot study to sequence 100 individuals each from Fula, Jola, Mandinka and Wollof from the Gambia to low coverage has been completed - this first part of the main effort will make available low coverage WGS data for 400 individuals from multiple ethnic groups in Burkina Faso, Cameroon, Ghana and Tanzania. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This project forms a central part of the Genomic Epidemiology of Malaria Project within the Sanger Quinquennial Plan. It uses DNA samples and clinical data that have been collected as part of an ongoing multi-centre study of severe malaria undertaken by MalariaGEN, coordinated jointly by the Sanger Institute and Oxford University.We have previously genotyped &gt;23,000 individuals from 11 countries using Illumina 2.5M SNP array. Although this array is much denser than previous generations of genotyping arrays, it is still too sparse to cover genetic variability in malaria-endemic populations. To get a denser marker map for a genome-wide association study (GWAS), we need to impute genotypes based on sequencing data. There are some publicly available reference sets for imputation provided by HapMap and the 1000 Genomes project. Unfortunately, African populations are under-represented in the available reference sets and most of the populations we have genotyped have no publicly available sequence data.We have previously tested the usefulness of Nigerian sequence data for imputation of genotypes in a Gambian GWAS around a known malaria resistance locus (HBB) - unfortunately the association signal was lost through imputation because these two populations have different haplotypic backgrounds in this locus. This is just one example of the level of genetic variability we have encountered in African populations, and underlines the fact that to impute genotypes successfully, we need to sequence individuals from the countries - and the ethnic groups within each country - that are represented in our GWAS.We have completed sequencing of 100 individuals each from four ethnic groups in the Gambia (Fula, Jola, Mandinka and Wollof), and the currect project will expand sequencing to other populations that are represented in our multi-centre GWAS of severe malaria. It will cover 1-2 ethnic groups each from Burkina Faso, Cameroon, Ghana and Tanzania to a total of400 individuals.The primary motive of this project is to maximise our power to detect association to malaria resistance/susceptibility but these data will also provide an information repository on genome variation and GWAS assay design in African populations, and will be highly complementary to other Sanger work in this area.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000638","title":"WGS_low_coverage_sequencing_of_Wasambaa_from_Tanzania","description":"We aim to provide a powerful reference set for genome-wide association studies (GWAS) in African populations. Our pilot study to sequence 100 individuals each from Fula, Jola, Mandinka and Wollof from the Gambia to low coverage has been completed - this first part of the main effort will make available low coverage WGS data for 400 individuals from multiple ethnic groups in Burkina Faso, Cameroon, Ghana and Tanzania. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This project forms a central part of the Genomic Epidemiology of Malaria Project within the Sanger Quinquennial Plan. It uses DNA samples and clinical data that have been collected as part of an ongoing multi-centre study of severe malaria undertaken by MalariaGEN, coordinated jointly by the Sanger Institute and Oxford University.We have previously genotyped &gt;23,000 individuals from 11 countries using Illumina 2.5M SNP array. Although this array is much denser than previous generations of genotyping arrays, it is still too sparse to cover genetic variability in malaria-endemic populations. To get a denser marker map for a genome-wide association study (GWAS), we need to impute genotypes based on sequencing data. There are some publicly available reference sets for imputation provided by HapMap and the 1000 Genomes project. Unfortunately, African populations are under-represented in the available reference sets and most of the populations we have genotyped have no publicly available sequence data.We have previously tested the usefulness of Nigerian sequence data for imputation of genotypes in a Gambian GWAS around a known malaria resistance locus (HBB) - unfortunately the association signal was lost through imputation because these two populations have different haplotypic backgrounds in this locus. This is just one example of the level of genetic variability we have encountered in African populations, and underlines the fact that to impute genotypes successfully, we need to sequence individuals from the countries - and the ethnic groups within each country - that are represented in our GWAS.We have completed sequencing of 100 individuals each from four ethnic groups in the Gambia (Fula, Jola, Mandinka and Wollof), and the currect project will expand sequencing to other populations that are represented in our multi-centre GWAS of severe malaria. It will cover 1-2 ethnic groups each from Burkina Faso, Cameroon, Ghana and Tanzania to a total of400 individuals.The primary motive of this project is to maximise our power to detect association to malaria resistance/susceptibility but these data will also provide an information repository on genome variation and GWAS assay design in African populations, and will be highly complementary to other Sanger work in this area.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000639","title":"WGS_low_coverage_sequencing_of_Zaramo_from_Tanzania","description":"We aim to provide a powerful reference set for genome-wide association studies (GWAS) in African populations. Our pilot study to sequence 100 individuals each from Fula, Jola, Mandinka and Wollof from the Gambia to low coverage has been completed - this first part of the main effort will make available low coverage WGS data for 400 individuals from multiple ethnic groups in Burkina Faso, Cameroon, Ghana and Tanzania. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This project forms a central part of the Genomic Epidemiology of Malaria Project within the Sanger Quinquennial Plan. It uses DNA samples and clinical data that have been collected as part of an ongoing multi-centre study of severe malaria undertaken by MalariaGEN, coordinated jointly by the Sanger Institute and Oxford University.We have previously genotyped &gt;23,000 individuals from 11 countries using Illumina 2.5M SNP array. Although this array is much denser than previous generations of genotyping arrays, it is still too sparse to cover genetic variability in malaria-endemic populations. To get a denser marker map for a genome-wide association study (GWAS), we need to impute genotypes based on sequencing data. There are some publicly available reference sets for imputation provided by HapMap and the 1000 Genomes project. Unfortunately, African populations are under-represented in the available reference sets and most of the populations we have genotyped have no publicly available sequence data.We have previously tested the usefulness of Nigerian sequence data for imputation of genotypes in a Gambian GWAS around a known malaria resistance locus (HBB) - unfortunately the association signal was lost through imputation because these two populations have different haplotypic backgrounds in this locus. This is just one example of the level of genetic variability we have encountered in African populations, and underlines the fact that to impute genotypes successfully, we need to sequence individuals from the countries – and the ethnic groups within each country – that are represented in our GWAS.We have completed sequencing of 100 individuals each from four ethnic groups in the Gambia (Fula, Jola, Mandinka and Wollof), and the currect project will expand sequencing to other populations that are represented in our multi-centre GWAS of severe malaria. It will cover 1-2 ethnic groups each from Burkina Faso, Cameroon, Ghana and Tanzania to a total of400 individuals.The primary motive of this project is to maximise our power to detect association to malaria resistance/susceptibility but these data will also provide an information repository on genome variation and GWAS assay design in African populations, and will be highly complementary to other Sanger work in this area.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000640","title":"WGS_low_coverage_sequencing_of_Dar_Es_Salaam_from_Tanzania","description":"We aim to provide a powerful reference set for genome-wide association studies (GWAS) in African populations. Our pilot study to sequence 100 individuals each from Fula, Jola, Mandinka and Wollof from the Gambia to low coverage has been completed - this first part of the main effort will make available low coverage WGS data for 400 individuals from multiple ethnic groups in Burkina Faso, Cameroon, Ghana and Tanzania. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This project forms a central part of the Genomic Epidemiology of Malaria Project within the Sanger Quinquennial Plan. It uses DNA samples and clinical data that have been collected as part of an ongoing multi-centre study of severe malaria undertaken by MalariaGEN, coordinated jointly by the Sanger Institute and Oxford University.We have previously genotyped &gt;23,000 individuals from 11 countries using Illumina 2.5M SNP array. Although this array is much denser than previous generations of genotyping arrays, it is still too sparse to cover genetic variability in malaria-endemic populations. To get a denser marker map for a genome-wide association study (GWAS), we need to impute genotypes based on sequencing data. There are some publicly available reference sets for imputation provided by HapMap and the 1000 Genomes project. Unfortunately, African populations are under-represented in the available reference sets and most of the populations we have genotyped have no publicly available sequence data.We have previously tested the usefulness of Nigerian sequence data for imputation of genotypes in a Gambian GWAS around a known malaria resistance locus (HBB) - unfortunately the association signal was lost through imputation because these two populations have different haplotypic backgrounds in this locus. This is just one example of the level of genetic variability we have encountered in African populations, and underlines the fact that to impute genotypes successfully, we need to sequence individuals from the countries - and the ethnic groups within each country - that are represented in our GWAS.We have completed sequencing of 100 individuals each from four ethnic groups in the Gambia (Fula, Jola, Mandinka and Wollof), and the currect project will expand sequencing to other populations that are represented in our multi-centre GWAS of severe malaria. It will cover 1-2 ethnic groups each from Burkina Faso, Cameroon, Ghana and Tanzania to a total of400 individuals.The primary motive of this project is to maximise our power to detect association to malaria resistance/susceptibility but these data will also provide an information repository on genome variation and GWAS assay design in African populations, and will be highly complementary to other Sanger work in this area.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000641","title":"Mutational context and diverse clonal development in early and late bladder cancer","description":"Bladder cancer shows multiple recurrences probably originating from a malignant field disease in the mucosa. Deep sequencing was used on a series of tumors to look into the clonal composition, mutational spectrum in non-aggressive tumors, and mutational context.","abstract":"Bladder cancer shows multiple recurrences probably originating from a malignant field disease in the mucosa. Deep sequencing was used on a series of tumors to look into the clonal composition, mutational spectrum in non-aggressive tumors, and mutational context.","study_type":"Other","pubmed_ids":[24835989],"external_links":null,"is_released":true,"released_date":"2013-11-26T09:58:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000642","title":"Quantification of chromosomal copy number aberrations by shallow whole-genome sequencing","description":"Detection of DNA copy number aberrations by shallow whole-genome sequencing (WGS) faces many challenges including lack of completion and errors in the human reference genome, repetitive sequences, polymorphisms, variable sample quality, and biases in the sequencing procedures.Formalin-fixed paraffin-embedded (FFPE) archival material, the analysis of which is important for studies of cancer, presents particular analytical difficulties due to degradation of the DNA and frequent lack of matched reference samples. We present a robust, cost-effective WGS method for DNA copy number analysis that addresses these challenges more successfully than currently available procedures. In practice very useful profiles can be obtained with 0.1 fold genome coverage. We improve on previous methods by; first, implementing a combined correction for sequence mappability and GC content, and second, applying this procedure to sequence data from the 1000 Genomes Project in order to develop a blacklist of problematic genome regions. A small subset of these blacklisted regions were previously identified by ENCODE, but the vast majority are novel unappreciated problematic regions. Our procedures are implemented in a pipeline called QDNAseq. We have analyzed over 1,000 samples, most of which were obtained from the fixed tissue archives of over 25 institutions.We demonstrate that for most samples our sequencing and analysis procedures yield genome profiles with noise levels near the statistical limit imposed by read counting. The described procedures also provide better correction of artifacts introduced by low DNA quality than prior approaches, and better copy number data than high-resolution microarrays at substantially lower cost.","abstract":"Detection of DNA copy number aberrations by shallow whole-genome sequencing (WGS) faces many challenges including lack of completion and errors in the human reference genome, repetitive sequences, polymorphisms, variable sample quality, and biases in the sequencing procedures.Formalin-fixed paraffin-embedded (FFPE) archival material, the analysis of which is important for studies of cancer, presents particular analytical difficulties due to degradation of the DNA and frequent lack of matched reference samples. We present a robust, cost-effective WGS method for DNA copy number analysis that addresses these challenges more successfully than currently available procedures. In practice very useful profiles can be obtained with 0.1 fold genome coverage. We improve on previous methods by; first, implementing a combined correction for sequence mappability and GC content, and second, applying this procedure to sequence data from the 1000 Genomes Project in order to develop a blacklist of problematic genome regions. A small subset of these blacklisted regions were previously identified by ENCODE, but the vast majority are novel unappreciated problematic regions. Our procedures are implemented in a pipeline called QDNAseq. We have analyzed over 1,000 samples, most of which were obtained from the fixed tissue archives of over 25 institutions.We demonstrate that for most samples our sequencing and analysis procedures yield genome profiles with noise levels near the statistical limit imposed by read counting. The described procedures also provide better correction of artifacts introduced by low DNA quality than prior approaches, and better copy number data than high-resolution microarrays at substantially lower cost.","study_type":"Other","pubmed_ids":[25236618],"external_links":null,"is_released":true,"released_date":"2013-11-27T11:34:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000643","title":"Spatial and temporal evolution of distal 10q deletion, a prognostically unfavorable event in diffuse low-grade gliomas","description":"Background: The disease course of patients with diffuse low-grade glioma is notoriously unpredictable. Temporal and spatially distinct samples may provide insight into the evolution of clinically relevant copy number aberrations (CNAs). The purpose of this study is to identify CNAs that are indicative of aggressive tumor behaviour and can thereby complement the prognostically favorable 1p/19q co-deletion. Results: Genome-wide, 50 base pair single-end, sequencing was performed to detect CNAs in a clinically well-characterized cohort of 98 formalin-fixed paraffin-embedded low-grade gliomas. CNAs are correlated with overall survival as an endpoint. Seventy-five additional samples from spatially distinct regions and paired recurrent tumors of the discovery cohort were analysed to interrogate the intratumoral heterogeneity and spatial evolution. Loss of 10q25.2-qter is a frequent subclonal event and significantly correlates with an unfavorable prognosis. A significant correlation is furthermore observed in a validation set of 126 and confirmation set of 184 patients. Loss of 10q25.2-qter arises in a longitudinal manner in paired recurrent tumor specimens, whereas the prognostically favorable 1p/ 19q co-deletion is the only CNA that is stable across spatial regions and recurrent tumors. Conclusions: CNAs in low-grade gliomas display extensive intratumoral heterogeneity. Distal loss of 10q is a late onset event and a marker for reduced overall survival in low-grade glioma patients. Intratumoral heterogeneity and higher frequencies of distal 10q loss in recurrences suggest this event is involved in outgrowth to the recurrent tumor.","abstract":"Background: The disease course of patients with diffuse low-grade glioma is notoriously unpredictable. Temporal and spatially distinct samples may provide insight into the evolution of clinically relevant copy number aberrations (CNAs). The purpose of this study is to identify CNAs that are indicative of aggressive tumor behaviour and can thereby complement the prognostically favorable 1p/19q co-deletion. Results: Genome-wide, 50 base pair single-end, sequencing was performed to detect CNAs in a clinically well-characterized cohort of 98 formalin-fixed paraffin-embedded low-grade gliomas. CNAs are correlated with overall survival as an endpoint. Seventy-five additional samples from spatially distinct regions and paired recurrent tumors of the discovery cohort were analysed to interrogate the intratumoral heterogeneity and spatial evolution. Loss of 10q25.2-qter is a frequent subclonal event and significantly correlates with an unfavorable prognosis. A significant correlation is furthermore observed in a validation set of 126 and confirmation set of 184 patients. Loss of 10q25.2-qter arises in a longitudinal manner in paired recurrent tumor specimens, whereas the prognostically favorable 1p/ 19q co-deletion is the only CNA that is stable across spatial regions and recurrent tumors. Conclusions: CNAs in low-grade gliomas display extensive intratumoral heterogeneity. Distal loss of 10q is a late onset event and a marker for reduced overall survival in low-grade glioma patients. Intratumoral heterogeneity and higher frequencies of distal 10q loss in recurrences suggest this event is involved in outgrowth to the recurrent tumor.","study_type":"Other","pubmed_ids":[25245118],"external_links":null,"is_released":true,"released_date":"2013-11-27T11:40:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000644","title":"Genome of the Netherlands","description":"The Genome of the Netherlands (GoNL) Project characterizes DNA sequence variation, common and rare, for SNVs, short insertions and deletions (indels) and larger deletions in 769 individuals of Dutch ancestry selected from five biobanks under the auspices of the Dutch hub of the Biobanking and Biomolecular Research Infrastructure (BBMRI-NL). The samples come from a representative sample of 250 trio-families from all provinces in the Netherlands. The parent-offspring trios include adult individuals ranging in age from 19 to 87 years (mean=53 years; SD=16 years) from birth cohorts 1910-1994. Sequencing was done on blood-derived DNA from uncultured cells and accomplished coverage was 14-15x. Samples where contributed by LifeLines (http://lifelines.nl/lifelines-research/general), The Leiden Longevity Study (http://www.healthy-ageing.nl; http://www.langleven.net), The Netherlands Twin Registry (NTR: http://www.tweelingenregister. org), The Rotterdam studies, (http://www.erasmus-epidemiology.nl/rotterdamstudy) and the Genetic Research in Isolated Populations program (http://www.epib.nl/research/geneticepi/research.html#gip). The sequencing was carried out in collaboration with the Beijing Institute for Genomics (BGI). The analysis was done by a consortium lead by UMCG, LUMC, Erasmus MC, VU university and UMCU, see http://www.nlgenome.nl. Funding for the project was provided by the Netherlands Organization for Scientific Research under award number 184021007, dated July 9, 2009 and made available as a Rainbow Project of the Biobanking and Biomolecular Research Infrastructure Netherlands (BBMRI-NL).","abstract":"The Genome of the Netherlands (GoNL) Project characterizes DNA sequence variation, common and rare, for SNVs, short insertions and deletions (indels) and larger deletions in 769 individuals of Dutch ancestry selected from five biobanks under the auspices of the Dutch hub of the Biobanking and Biomolecular Research Infrastructure (BBMRI-NL). The samples come from a representative sample of 250 trio-families from all provinces in the Netherlands. The parent-offspring trios include adult individuals ranging in age from 19 to 87 years (mean=53 years; SD=16 years) from birth cohorts 1910-1994. Sequencing was done on blood-derived DNA from uncultured cells and accomplished coverage was 14-15x. Samples where contributed by LifeLines (http://lifelines.nl/lifelines-research/general), The Leiden Longevity Study (http://www.healthy-ageing.nl; http://www.langleven.net), The Netherlands Twin Registry (NTR: http://www.tweelingenregister. org), The Rotterdam studies, (http://www.erasmus-epidemiology.nl/rotterdamstudy) and the Genetic Research in Isolated Populations program (http://www.epib.nl/research/geneticepi/research.html#gip). The sequencing was carried out in collaboration with the Beijing Institute for Genomics (BGI). The analysis was done by a consortium lead by UMCG, LUMC, Erasmus MC, VU university and UMCU, see http://www.nlgenome.nl. Funding for the project was provided by the Netherlands Organization for Scientific Research under award number 184021007, dated July 9, 2009 and made available as a Rainbow Project of the Biobanking and Biomolecular Research Infrastructure Netherlands (BBMRI-NL).","study_type":"Other","pubmed_ids":[23714750,24896149,24974849],"external_links":null,"is_released":true,"released_date":"2013-11-28T13:50:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000645","title":"Next Generation Sequencing of clinical data related with the Breast Cancer as well as Cystic fibrosis","description":"Evaluation of the Next Generation Sequencing and especially the Miseq platform in the everyday clinical diagnostic laboratory. We evaluate with Coriell smaples the accuracy, sensitivity and specificity, the cost, the speed of sequencing with Miseq the whole genes BRCA1,2 and the CFTR","abstract":"Evaluation of the Next Generation Sequencing and especially the Miseq platform in the everyday clinical diagnostic laboratory. We evaluate with Coriell smaples the accuracy, sensitivity and specificity, the cost, the speed of sequencing with Miseq the whole genes BRCA1,2 and the CFTR","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000646","title":"The study provides comprehensive access to the set of EGA studies which may be useful as controls.","description":"The subjects studies in these datasets were selected due to being healthy control individuals or otherwise provide well characterised phenotype or exclude certain disease phenotype categories such that they may be useful as control population, such as to derive allele frequencies from a known reference population.","abstract":"The subjects studies in these datasets were selected due to being healthy control individuals or otherwise provide well characterised phenotype or exclude certain disease phenotype categories such that they may be useful as control population, such as to derive allele frequencies from a known reference population.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-12-06T19:27:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000647","title":"A Genomics-Based Classification of Human Lung Tumors","description":"We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment approaches that are already in clinical evaluation. Marked differences in the pattern of genomic alterations existed between and within histological subtypes, thus challenging the original histomorphological diagnosis. Immunohistochemical studies confirmed many of these reassigned subtypes. The reassignment eliminated almost all cases of large cell carcinomas, some of which had therapeutically relevant alterations. Prospective testing of our genomics-based diagnostic algorithm in 5145 lung cancer patients enabled a genome-based diagnosis in 3863 (75%) patients, confirmed the feasibility of rational reassignments of large cell lung cancer, and led to improvement in overall survival in patients with EGFR-mutant or ALK-rearranged cancers. Thus, our findings provide support for broad implementation of genome-based diagnosis of lung cancer.","abstract":"We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment approaches that are already in clinical evaluation. Marked differences in the pattern of genomic alterations existed between and within histological subtypes, thus challenging the original histomorphological diagnosis. Immunohistochemical studies confirmed many of these reassigned subtypes. The reassignment eliminated almost all cases of large cell carcinomas, some of which had therapeutically relevant alterations. Prospective testing of our genomics-based diagnostic algorithm in 5145 lung cancer patients enabled a genome-based diagnosis in 3863 (75%) patients, confirmed the feasibility of rational reassignments of large cell lung cancer, and led to improvement in overall survival in patients with EGFR-mutant or ALK-rearranged cancers. Thus, our findings provide support for broad implementation of genome-based diagnosis of lung cancer.","study_type":"Other","pubmed_ids":[24174329],"external_links":null,"is_released":true,"released_date":"2013-12-10T09:49:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000648","title":"FinHer_Breast_Cancer_Study","description":"The purpose of this study is to sequence 500 known cancer genes in 960 newly diagnosed high risk breast cancer patients treated with current standard of care therapies and trastuzumab, for somatic alteration and copy number changes. We will be using next gen sequencing technology to determine the prognostic relevance of these somatic genetic alterations and of teh low frequency events to determine if they are associated with trastuzumab benefit or HER2 positive breast cancer, i.e. treatment interaction. The samples will be analysed adn correlated with clinical variables including outcome.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-12-11T12:49:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000649","title":"GEL_WGS_Comparison","description":"These samples are to be analysed with the CGP Developed cancer panel and the results will be compared with WGS data from 4 different comercial providers.","abstract":"These samples are to be analysed with the CGP Developed cancer panel and the results will be compared with WGS data from 4 different comercial providers.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-12-11T18:10:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000650","title":"Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids","description":"Pulmonary carcinoids are rare neuroendocrine tumours of the lung. The molecular alterations underlying the pathogenesis of these tumours have not been systematically studied so far. Here we perform gene copy number analysis (n¼54), genome/exome (n¼44) and transcriptome (n¼69) sequencing of pulmonary carcinoids and observe frequent mutations in chromatin-remodelling genes. Covalent histone modifiers and subunits of the SWI/SNF complex are mutated in 40 and 22.2% of the cases, respectively, with MEN1, PSIP1 and ARID1A being recurrently affected. In contrast to small-cell lung cancer and large-cell neuroendocrine tumours, TP53 and RB1 mutations are rare events, suggesting that pulmonary carcinoids are not early progenitor lesions of the highly aggressive lung neuroendocrine tumors but arise through independent cellular mechanisms. These data also suggest that inactivation of chromatinremodelling genes is sufficient to drive transformation in pulmonary carcinoids.","abstract":"Pulmonary carcinoids are rare neuroendocrine tumours of the lung. The molecular alterations underlying the pathogenesis of these tumours have not been systematically studied so far. Here we perform gene copy number analysis (n¼54), genome/exome (n¼44) and transcriptome (n¼69) sequencing of pulmonary carcinoids and observe frequent mutations in chromatin-remodelling genes. Covalent histone modifiers and subunits of the SWI/SNF complex are mutated in 40 and 22.2% of the cases, respectively, with MEN1, PSIP1 and ARID1A being recurrently affected. In contrast to small-cell lung cancer and large-cell neuroendocrine tumours, TP53 and RB1 mutations are rare events, suggesting that pulmonary carcinoids are not early progenitor lesions of the highly aggressive lung neuroendocrine tumors but arise through independent cellular mechanisms. These data also suggest that inactivation of chromatinremodelling genes is sufficient to drive transformation in pulmonary carcinoids.","study_type":"Other","pubmed_ids":[24670920],"external_links":null,"is_released":true,"released_date":"2013-12-12T13:55:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000651","title":"Mutational_Signatures_of_relapse_in_rectal_cancer_FFPE_samples_in_the_CR07_clinical_trial","description":"The CRO7 clinical trial recruited patients with clinically operable rectal adenocarcinoma. Patients were randomized to either pre-operative short course surgery followed by chemo-radiotherapy only in those patients at high risk of local relapse. Patients in both arms the received standard %-FU based adjuvant chemotherapy as per local policy. We intend to use FFPE derived DNA from the primary tumours to identify patterns of mutations or copy number alterations that are predictive of local or distant relapse.","abstract":"DNA derived from FFPE tissue cancer specimens will be hybridised using custom set of Agilent sureselect RNA baits targeting cancer genes followed by Illumina sequencing.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-12-13T14:06:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000652","title":"Microsatellite data show recent demographic expansions in sedentary but not in nomadic human populations in Africa and Eurasia.","description":"The transition from hunting and gathering to plant and animal domestication was one of the most important cultural and technological revolutions in human history. According to archeologists and paleoanthropologists, this transition triggered major demographic expansions. However, few genetic studies have found traces of Neolithic expansions in the current repartition of genetic polymorphism, pointing rather toward Paleolithic expansions. Here, we used microsatellite autosomal data to investigate the past demographic history of 87 African and Eurasian human populations with contrasted lifestyles (nomadic hunter-gatherers, semi-nomadic herders and sedentary farmers). Likely due to the combination of a higher mutation rate and the possibility to analyze several loci as independent replicates of the coalescent process, the analysis of microsatellite data allowed us to infer more recent expansions than previous genetic studies, potentially resulting from the Neolithic transition. Despite the variability in their location and environment, we found consistent expansions for all sedentary farmers, while we inferred constant population sizes for all hunter-gatherers and most herders, which could result from constraints linked to a nomadic or semi-nomadic lifestyle and/or competition for land between herders and farmers. As an exception, we inferred expansions for Central Asian herders. This might be linked with the arid environment of this area, which may have been more favorable to nomadic herders than to sedentary farmers. Alternatively, current Central Asian herders may descent from populations who have first experienced a transition from hunter-gathering to sedentary agropastoralism, and then a second transition to nomadic herding.","abstract":"The transition from hunting and gathering to plant and animal domestication was one of the most important cultural and technological revolutions in human history. According to archeologists and paleoanthropologists, this transition triggered major demographic expansions. However, few genetic studies have found traces of Neolithic expansions in the current repartition of genetic polymorphism, pointing rather toward Paleolithic expansions. Here, we used microsatellite autosomal data to investigate the past demographic history of 87 African and Eurasian human populations with contrasted lifestyles (nomadic hunter-gatherers, semi-nomadic herders and sedentary farmers). Likely due to the combination of a higher mutation rate and the possibility to analyze several loci as independent replicates of the coalescent process, the analysis of microsatellite data allowed us to infer more recent expansions than previous genetic studies, potentially resulting from the Neolithic transition. Despite the variability in their location and environment, we found consistent expansions for all sedentary farmers, while we inferred constant population sizes for all hunter-gatherers and most herders, which could result from constraints linked to a nomadic or semi-nomadic lifestyle and/or competition for land between herders and farmers. As an exception, we inferred expansions for Central Asian herders. This might be linked with the arid environment of this area, which may have been more favorable to nomadic herders than to sedentary farmers. Alternatively, current Central Asian herders may descent from populations who have first experienced a transition from hunter-gathering to sedentary agropastoralism, and then a second transition to nomadic herding.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-12-13T14:22:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000653","title":"CD74-NRG1 fusions in lung adenocarcinoma","description":"We discovered a novel somatic gene fusion, CD74-NRG1, by transcriptome sequencing of 25 lung adenocarcinomas of never smokers. By screening 102 lung adenocarcinomas negative for known oncogenic alterations we found four additional fusion-positive tumors, all of which were of the invasive mucinous subtype. Mechanistically, CD74-NRG1 leads to extracellular expression of the EGF-like domain of NRG1 III-beta3, thereby providing the ligand for ERBB2-ERBB3 receptor complexes. Accordingly, ERBB2 and ERBB3 expression was high in the index case and expression of phospho-ERBB3 was specifically found in tumors bearing the fusion (p&lt;0.0001). Ectopic expression of CD74-NRG1 in lung cancer cell lines expressing ERBB2 and ERBB3 activated ERBB3 and the PI3K-AKT pathway, and led to increased colony formation in soft agar. Thus, CD74-NRG1 gene fusions are activating genomic alterations in invasive mucinous adenocarcinomas and may offer a therapeutic opportunity for a lung tumor subtype with, so far, no effective treatment.","abstract":"We discovered a novel somatic gene fusion, CD74-NRG1, by transcriptome sequencing of 25 lung adenocarcinomas of never smokers. By screening 102 lung adenocarcinomas negative for known oncogenic alterations we found four additional fusion-positive tumors, all of which were of the invasive mucinous subtype. Mechanistically, CD74-NRG1 leads to extracellular expression of the EGF-like domain of NRG1 III-beta3, thereby providing the ligand for ERBB2-ERBB3 receptor complexes. Accordingly, ERBB2 and ERBB3 expression was high in the index case and expression of phospho-ERBB3 was specifically found in tumors bearing the fusion (p&lt;0.0001). Ectopic expression of CD74-NRG1 in lung cancer cell lines expressing ERBB2 and ERBB3 activated ERBB3 and the PI3K-AKT pathway, and led to increased colony formation in soft agar. Thus, CD74-NRG1 gene fusions are activating genomic alterations in invasive mucinous adenocarcinomas and may offer a therapeutic opportunity for a lung tumor subtype with, so far, no effective treatment.","study_type":"Other","pubmed_ids":[24469108],"external_links":null,"is_released":true,"released_date":"2013-12-17T11:22:18+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000654","title":"PCGP Ph-like ALL","description":"Background: BCR-ABL1-like, or Ph-like acute lymphoblastic leukemia is characterized by a gene expression profile similar to BCR-ABL1 positive ALL, genetic alterations of lymphoid transcription factor genes, and poor outcome. Sequencing of small numbers of Ph-like ALL cases has identified genetic alterations activating kinase signaling suggesting Ph-like ALL may be amenable to treatment with tyrosine kinase inhibitors. However, the spectrum of genetic alterations in childhood and adult Ph-like ALL is incompletely understood. Methods: We performed genomic profiling of 1736 B-ALL cases and next-generation sequencing for 160 Ph-like cases. We examined the functional effects of chimeric fusion proteins in mouse cell lines.  Results: The frequency of Ph-like ALL rose from 11% in children to 26% in young adults, and was associated with very poor outcome. Kinase-activating alterations were identified in 90% of Ph-like cases, most commonly fusions involving 10 kinase or cytokine receptor genes (ABL1, ABL2, CRLF2, CSF1R, EPOR, JAK2, NTRK3, PDGFRB, PTK2B and TYK2), and mutations involving FLT3, IL7R and SH2B3. Expression of ABL1, ABL2, CSF1R and JAK2 fusions resulted in cytokine-independent proliferation of cell lines and activation of pSTAT5. Cells expressing ABL1, ABL2, CSF1R and PDGFRB fusions were sensitive to dasatinib, and JAK2 fusions to ruxolitinib.  Conclusions: Ph-like ALL is characterized by a diverse range of genomic alterations that converge on a limited number of kinase signaling pathways amenable to inhibition with currently available tyrosine kinase inhibitors. Trials identifying Ph-like ALL and testing the efficacy of tyrosine kinase inhibitor therapy are warranted","abstract":"Background: BCR-ABL1-like, or Ph-like acute lymphoblastic leukemia is characterized by a gene expression profile similar to BCR-ABL1 positive ALL, genetic alterations of lymphoid transcription factor genes, and poor outcome. Sequencing of small numbers of Ph-like ALL cases has identified genetic alterations activating kinase signaling suggesting Ph-like ALL may be amenable to treatment with tyrosine kinase inhibitors. However, the spectrum of genetic alterations in childhood and adult Ph-like ALL is incompletely understood. Methods: We performed genomic profiling of 1736 B-ALL cases and next-generation sequencing for 160 Ph-like cases. We examined the functional effects of chimeric fusion proteins in mouse cell lines.  Results: The frequency of Ph-like ALL rose from 11% in children to 26% in young adults, and was associated with very poor outcome. Kinase-activating alterations were identified in 90% of Ph-like cases, most commonly fusions involving 10 kinase or cytokine receptor genes (ABL1, ABL2, CRLF2, CSF1R, EPOR, JAK2, NTRK3, PDGFRB, PTK2B and TYK2), and mutations involving FLT3, IL7R and SH2B3. Expression of ABL1, ABL2, CSF1R and JAK2 fusions resulted in cytokine-independent proliferation of cell lines and activation of pSTAT5. Cells expressing ABL1, ABL2, CSF1R and PDGFRB fusions were sensitive to dasatinib, and JAK2 fusions to ruxolitinib.  Conclusions: Ph-like ALL is characterized by a diverse range of genomic alterations that converge on a limited number of kinase signaling pathways amenable to inhibition with currently available tyrosine kinase inhibitors. Trials identifying Ph-like ALL and testing the efficacy of tyrosine kinase inhibitor therapy are warranted","study_type":"Other","pubmed_ids":[25207766],"external_links":null,"is_released":true,"released_date":"2013-12-17T14:52:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000655","title":"Combination_therapies_for_personalized_cancer_medicine","description":"It is the ambition of the team formed by members of the Netherlands Cancer Institute (NKI) and the Cancer Genome Project at the Wellcome Trust Sanger Institute (WTSI) to unravel the genomic and phenotypic complexity of human cancers in order to identify optimal drug combinations for personalized cancer therapy. Our integrated approach will entail (i) deep sequencing of human tumours and cognate mouse tumours; (ii) drug screens in a 1000+ fully characterized tumour cell line panel; (iii) high-throughput in vitro and in vivo shRNA and cDNA drug resistance and enhancement screens; (iv) computational analysis of the acquired data, leading to significant response predictions; (v) rigorous validation of these predictions in genetically engineered mouse models and patient-derived xenografts. This integrated effort is expected to yield a number of combination therapies and companion-diagnostics biomarkers that will be further explored in our existing clinical trial networks.","abstract":"All cancers arise due to alterations in their genomes. Although insight into the genetic lesions in tumours by genome sequencing does already assist in selecting some drug regimens, it rarely results in disease eradication due to the emergence of drug-resistant clones. More sophisticated combination therapies in which several oncogenic pathways are targeted simultaneously or in a particular sequence are believed to hold more promise. However, at present we are unable to extract and interpret the necessary information from tumours to predict which drug regimen will be most adequate. The genetic make-up of the individual, the heterogeneity of the tumour, epigenetic alterations, cell-of-origin of the tumour, and complex interactions between tumour cells and stromal cells appear important confounding factors influencing response. In addition, we are still ignorant of many of the intricate complexities of signalling networks in cells and how tumours exploit these to acquire drug resistance.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-12-17T18:36:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000656","title":"Genetic_and_molecular_evolution_of_pancreatic_cancer_in_carriers_of_pathogenic_mutations_in_the_BRCA2_breast_cancer_susceptibility_gene","description":"We propose to utilise next generation sequencing in order to comprehensively catalogue the full compendium of mutations present in the coding exons of genes and microRNAs in the largest to date collection of pancreatic tumours in carriers of pathogenic BRCA2 mutations. This bio-resource has been assembled as a result of collaborations with three different research groups/consortia a) Professor Eyfjord and Professor Jonasson in the University of Iceland/Icelandic Cancer Registry, b) Professor Sabine Linn at the Netherlands Cancer Institute, and c) the kConFab Consortium in Australia.","abstract":"Inherited deleterious mutations in the BRCA2 breast cancer susceptibility gene afflict mutation carriers with a 3.5-10 fold elevated lifetime risk of developing pancreatic cancer and represent the most prevalent identifiable genetic alteration in families with clustering of pancreatic cancer cases. Using a novel murine model of familial pancreatic cancer, a hitherto unrecognised role for BRCA2 haplo-insufficiency in promoting pancreatic carcinogenesis driven by oncogenic KrasG12D has been reported(Skoulidis et al, 2010), thus challenging the widely held notion that early loss of the wild type BRCA2 allele in tumour-initiating cells is an obligate and thus ubiquitous event that underpins tumour development in mutation carriers. Furthermore, this study suggested that human pancreatic tumours with early bi-allelic BRCA2 inactivation frequently develop as acinar cell carcinomas – normally a rare pancreatic neoplasm – whereas retention of the wild type BRCA2 allele, at least until later stages of tumour evolution, fosters the development of typical pancreatic ductal adenocarcinomas (PDAC).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000657","title":"The BC Cancer Agency’s Personalized Onco-Genomics Project","description":"The BC Cancer Agency’s Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","abstract":"The BC Cancer Agency’s Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001000658","title":"Illumina Human Exome (ExomeChip) genotype data from the Pomak villages in Greece (HELIC Pomak Isolate). 1040 samples all >=16 years old.","description":"Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies. Here we have genotyped individuals from a Greek population isolate on the Illumina HumanExome Beadchip. The HELIC (Hellenic Isolated Cohorts) Pomak collection focuses on the Pomak villages in Greece. Recruitment of this population-based sample was primarily carried out at the village medical centres. www.helic.org","abstract":"Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies. Here we have genotyped individuals from a Greek population isolate on the Illumina HumanExome Beadchip. The HELIC (Hellenic Isolated Cohorts) Pomak collection focuses on the Pomak villages in Greece. Recruitment of this population-based sample was primarily carried out at the village medical centres. www.helic.org","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-08-19T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000659","title":"Identification of novel fusion genes in lung cancer using breakpoint assembly of transcriptome sequencing data","description":"Genomic translocation events frequently underlie cancer development through generation of gene fusions with oncogenic properties. Identification of such fusion transcripts by transcriptome sequencing might help to discover new potential therapeutic targets. We developed TRUP (Tumor-specimen suited RNA-seq Unified Pipeline (https://github.com/ruping/TRUP), a computational approach that combines split-read and read-pair analysis with de-novo assembly for the identification of chimeric transcripts in cancer specimens. We apply TRUP to RNA-seq data of different tumor types, and find it to be more sensitive than alternative tools in detecting chimeric transcripts, such as secondaryrearrangements in EML4-ALK-positive lung tumors, or recurrent inactivating rearrangements affecting RASSF8.","abstract":"Genomic translocation events frequently underlie cancer development through generation of gene fusions with oncogenic properties. Identification of such fusion transcripts by transcriptome sequencing might help to discover new potential therapeutic targets. We developed TRUP (Tumor-specimen suited RNA-seq Unified Pipeline (https://github.com/ruping/TRUP), a computational approach that combines split-read and read-pair analysis with de-novo assembly for the identification of chimeric transcripts in cancer specimens. We apply TRUP to RNA-seq data of different tumor types, and find it to be more sensitive than alternative tools in detecting chimeric transcripts, such as secondaryrearrangements in EML4-ALK-positive lung tumors, or recurrent inactivating rearrangements affecting RASSF8.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-12-23T13:17:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000660","title":"High number of somatic mutations found in the healthy blood compartment of a 115-year-old woman reveals oligoclonal hematopoiesis","description":"The somatic mutation burden in healthy white blood cells (WBCs) is not well known. Based on deep whole genome sequencing, we estimate that ~450 somatic mutations accumulated in the non-repetitive genome within the healthy blood compartment of a 115-year old woman. The detected mutations appear to have been harmless passenger mutations: they were enriched in non-coding, AT-rich regions that are not evolutionarily conserved, and they were depleted for genomic elements where mutations might have favorable or adverse effects on cellular fitness, such as regions with actively transcribed genes.The distribution of variant allele frequencies of these mutations suggests that the majority of the peripheral white blood cells were offspring of two related hematopoietic stem cell (HSC) clones. Moreover, telomere lengths of the WBCs were significantly shorter than telomere lengths from other tissues. Together, this suggests that the finite lifespan of HSCs, rather than somatic mutation effects, may lead to hematopoietic clonal evolution at extreme ages.","abstract":"The somatic mutation burden in healthy white blood cells (WBCs) is not well known. Based on deep whole genome sequencing, we estimate that ~450 somatic mutations accumulated in the non-repetitive genome within the healthy blood compartment of a 115-year old woman. The detected mutations appear to have been harmless passenger mutations: they were enriched in non-coding, AT-rich regions that are not evolutionarily conserved, and they were depleted for genomic elements where mutations might have favorable or adverse effects on cellular fitness, such as regions with actively transcribed genes.The distribution of variant allele frequencies of these mutations suggests that the majority of the peripheral white blood cells were offspring of two related hematopoietic stem cell (HSC) clones. Moreover, telomere lengths of the WBCs were significantly shorter than telomere lengths from other tissues. Together, this suggests that the finite lifespan of HSCs, rather than somatic mutation effects, may lead to hematopoietic clonal evolution at extreme ages.","study_type":"Other","pubmed_ids":[24760347],"external_links":null,"is_released":true,"released_date":"2013-12-24T10:02:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000661","title":"Whole-exome analysis of corticotropin-independent Cushing's syndrome","description":"We performed WES for 8 cases with corticotropin-independent Cushing’s syndrome, in whom paired tumor and normal DNA was obtained from fresh frozen adenomas and either normal adrenal tissues or peripheral blood, respectively.","abstract":"We performed WES for 8 cases with corticotropin-independent Cushing’s syndrome, in whom paired tumor and normal DNA was obtained from fresh frozen adenomas and either normal adrenal tissues or peripheral blood, respectively.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2013-12-26T10:05:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000662","title":"Biallelic DICER1 mutations in sporadic pleuropulmonary blastoma","description":"Pleuropulmonary blastoma (PPB) is an extremely rare pediatric malignancy in the lung, whose pathogenesis is poorly understood, except for recent reports of frequent germline heterozygous DICER1 mutations.  To investigate the genetic basis of PPB, we performed whole-exome sequencing in 7 representative PPB cases, followed by targeted deep sequencing in 12 cases with PPB.  DICER1 mutations were found in 11/12 cases.  Biallelic DICER1 mutations were common in PPB, in which RNase IIIb domain mutations were found in all cases with or without nonsense/frameshift mutations and were somatic in all evaluable cases.  A majority of cases had mutated DICER1 alleles in germline with or without an additional somatic mutation in the remaining allele, while other cases had exclusively somatic mutations involving the RNase IIIb domain.  TP53 deletions/mutations were detected in 8/12 cases.  Our results highlight a unique role of the RNase IIIb domain mutations and TP53 inactivation in PPB pathogenesis.","abstract":"Pleuropulmonary blastoma (PPB) is an extremely rare pediatric malignancy in the lung, whose pathogenesis is poorly understood, except for recent reports of frequent germline heterozygous DICER1 mutations.  To investigate the genetic basis of PPB, we performed whole-exome sequencing in 7 representative PPB cases, followed by targeted deep sequencing in 12 cases with PPB.  DICER1 mutations were found in 11/12 cases.  Biallelic DICER1 mutations were common in PPB, in which RNase IIIb domain mutations were found in all cases with or without nonsense/frameshift mutations and were somatic in all evaluable cases.  A majority of cases had mutated DICER1 alleles in germline with or without an additional somatic mutation in the remaining allele, while other cases had exclusively somatic mutations involving the RNase IIIb domain.  TP53 deletions/mutations were detected in 8/12 cases.  Our results highlight a unique role of the RNase IIIb domain mutations and TP53 inactivation in PPB pathogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-01-09T03:08:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000663","title":"MPN_mutation_order_followup","description":"To evaluate the presence of mutations in frequently mutated genes in MPN by performing targeted resequencing of a selected gene panel comprising of 111 genes across 40 samples with MPN.","abstract":"Mutations will be called using standard in house algorithms including CAVEMAN and PINDEL and variants will be annotated as per recently developed pipelines (Papaemmanuil et al). Signifcant gene-gene interactions will be reported and variant allele fraction estimates will be computed and corrected, retrieving unmapped reads to support precise clonal phylogeny estimates.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-01-09T10:47:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000664","title":"Whole-Genome Sequencing of 128 Ashkenazi Jewish individuals","description":"We sequenced 128 individuals of Ashkenazi Jewish ancestry. All individuals were controls in other studies:  (1) Longevity (Gil Atzmon's lab; Albert Einstein College of Medicine), n=74. (2) Parkinson's disease (Lorraine Clark's lab; Columbia University Medical Center), n=54.  Whole-genome, high-coverage (50x) sequencing was performed by Complete Genomics in 2012 and 2013.","abstract":"We sequenced 128 individuals of Ashkenazi Jewish ancestry. All individuals were controls in other studies:  (1) Longevity (Gil Atzmon's lab; Albert Einstein College of Medicine), n=74. (2) Parkinson's disease (Lorraine Clark's lab; Columbia University Medical Center), n=54.  Whole-genome, high-coverage (50x) sequencing was performed by Complete Genomics in 2012 and 2013.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-01-09T23:02:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000665","title":"Integrated genomic characterization of adrenocortical carcinoma","description":"Adrenocortical carcinomas (ACC) are aggressive cancers originating in the cortex of the adrenal glands. Despite the overall poor prognosis, ACC outcome is heterogeneous. CTNNB1 and TP53 mutations are frequent in these tumors, but the complete spectrum of genetic changes remains undefined.  Exome sequencing and SNP array analysis of 45 ACC revealed recurrent alterations in known drivers (CTNNB1, TP53, CDKN2A, RB1,  MEN1)  and genes not previously reported to be altered in ACC (ZNRF3, DAXX, TERT and MED12), which were validated in an independent cohort of 77 ACC.  The cell-surface transmembrane E3 ubiquitin ligase ZNRF36 was the gene the most frequently altered (21%), and appears as a potential novel tumor suppressor gene related to the ß-catenin pathway. Our integrated genomic analyses led to the identification of two distinct molecular subgroups with opposite outcome. The C1A group of poor outcome ACC was characterized by numerous mutations and DNA methylation alterations, whereas the C1B group with good prognosis displayed a specific deregulation of two miRNA clusters.  Thus, aggressive and indolent ACC correspond to two distinct molecular entities, driven by different oncogenic alterations.Array based dataset for this study has been made public at:http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE49280.","abstract":"Adrenocortical carcinomas (ACC) are aggressive cancers originating in the cortex of the adrenal glands. Despite the overall poor prognosis, ACC outcome is heterogeneous. CTNNB1 and TP53 mutations are frequent in these tumors, but the complete spectrum of genetic changes remains undefined.  Exome sequencing and SNP array analysis of 45 ACC revealed recurrent alterations in known drivers (CTNNB1, TP53, CDKN2A, RB1,  MEN1)  and genes not previously reported to be altered in ACC (ZNRF3, DAXX, TERT and MED12), which were validated in an independent cohort of 77 ACC.  The cell-surface transmembrane E3 ubiquitin ligase ZNRF36 was the gene the most frequently altered (21%), and appears as a potential novel tumor suppressor gene related to the ß-catenin pathway. Our integrated genomic analyses led to the identification of two distinct molecular subgroups with opposite outcome. The C1A group of poor outcome ACC was characterized by numerous mutations and DNA methylation alterations, whereas the C1B group with good prognosis displayed a specific deregulation of two miRNA clusters.  Thus, aggressive and indolent ACC correspond to two distinct molecular entities, driven by different oncogenic alterations.Array based dataset for this study has been made public at:http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE49280.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-01-13T15:41:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000666","title":"Study_2","description":"Study_2","abstract":"Study_2","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000667","title":"Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing","description":"We applied multi-region exome sequencing to 10 clear cell renal carcinomas to resolve the genetic architecture, intra tumour heterogeneity and evolutionary histories of these tumours.","abstract":"We applied multi-region exome sequencing to 10 clear cell renal carcinomas to resolve the genetic architecture, intra tumour heterogeneity and evolutionary histories of these tumours.","study_type":"Other","pubmed_ids":[24487277],"external_links":null,"is_released":true,"released_date":"2014-01-14T15:34:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000668","title":"Study on the consequences of prenatal famine exposure on DNA methylation.","description":"The potential of the epigenome to undergo environmentally-induced changes during early development is central to its postulated role in human disease. Here, we report a genome-scale view of DNA methylation differences after early gestational malnutrition that was caused by the Dutch Hunger Winter, a severe famine at the end of World War II. We adopted an annotation guided analysis of reduced-representation bisulfite sequencing data generated in 24 middle-aged individuals who had been exposed to famine in utero and 24 unexposed sibling controls.  We observed differential DNA methylation primarily at genomic regions with regulatory potential, including enhancers active during early development. In-depth annotation of 181 prenatally-induced differentially methylated regions (P-DMRs) showed that they were predominantly located in gene bodies and co-occurred with histone marks denoting an active state. In line with the early gestational timing of the exposure, the P-DMRs mapped to genes that were enriched for differential expression patterns during blastocyst development and early organogenesis. Validation and further explorative analyses of 6 P-DMRs mapping to SMAD7, CDH23, INSR, RFTN1, CPT1A and KLF13 highlighted the critical role of gestational timing, indicated that differential methylation extended along pathways involved in growth, development and metabolism, and suggested associations with birth weight and serum LDL cholesterol in adulthood and confirmed an enhancer function for the INSR and CPT1A P-DMRs.  Our results point toward a link between prenatal malnutrition and epigenetic modulation of growth and lipid metabolism that may underlie the adverse metabolic phenotype of exposed individuals in later life.","abstract":"The potential of the epigenome to undergo environmentally-induced changes during early development is central to its postulated role in human disease. Here, we report a genome-scale view of DNA methylation differences after early gestational malnutrition that was caused by the Dutch Hunger Winter, a severe famine at the end of World War II. We adopted an annotation guided analysis of reduced-representation bisulfite sequencing data generated in 24 middle-aged individuals who had been exposed to famine in utero and 24 unexposed sibling controls.  We observed differential DNA methylation primarily at genomic regions with regulatory potential, including enhancers active during early development. In-depth annotation of 181 prenatally-induced differentially methylated regions (P-DMRs) showed that they were predominantly located in gene bodies and co-occurred with histone marks denoting an active state. In line with the early gestational timing of the exposure, the P-DMRs mapped to genes that were enriched for differential expression patterns during blastocyst development and early organogenesis. Validation and further explorative analyses of 6 P-DMRs mapping to SMAD7, CDH23, INSR, RFTN1, CPT1A and KLF13 highlighted the critical role of gestational timing, indicated that differential methylation extended along pathways involved in growth, development and metabolism, and suggested associations with birth weight and serum LDL cholesterol in adulthood and confirmed an enhancer function for the INSR and CPT1A P-DMRs.  Our results point toward a link between prenatal malnutrition and epigenetic modulation of growth and lipid metabolism that may underlie the adverse metabolic phenotype of exposed individuals in later life.","study_type":"Other","pubmed_ids":[25424739],"external_links":null,"is_released":true,"released_date":"2014-01-15T11:56:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000669","title":"An oncogenic enhancer-rearrangement causes concomitant deregulation of EVI1 and GATA2 in leukemia. Targeted resequencing of chromosomal regions centered on 3q21 and 3q26 in conjunction with RNA-Seq from Acute Myeloid Leukemia patients.","description":"Chromosomal rearrangements without gene-fusions have been implicated in leukemogenesis by causing deregulation of proto-oncogenes via relocation of cryptic regulatory DNA elements. AML with inv(3)/t(3;3) is associated with aberrant expression of the stem-cell regulator EVI1. Applying functional genomics and genome-engineering, we demonstrate that both 3q-rearrangements reposition a distal GATA2 enhancer to ectopically activate EVI1 and simultaneously confer GATA2 functional haploinsufficiency, previously identified as the cause of sporadic familial AML/MDS and MonoMac/Emberger syndromes. Genomic excision of the ectopic enhancer restored EVI1 silencing and led to growth inhibition and differentiation of AML cells, which could be replicated by pharmacologic BET-inhibition. Our data show that structural rearrangements involving chromosomal repositioning of enhancers can cause deregulation of two unrelated distal genes, with cancer as the outcome.","abstract":"Chromosomal rearrangements without gene-fusions have been implicated in leukemogenesis by causing deregulation of proto-oncogenes via relocation of cryptic regulatory DNA elements. AML with inv(3)/t(3;3) is associated with aberrant expression of the stem-cell regulator EVI1. Applying functional genomics and genome-engineering, we demonstrate that both 3q-rearrangements reposition a distal GATA2 enhancer to ectopically activate EVI1 and simultaneously confer GATA2 functional haploinsufficiency, previously identified as the cause of sporadic familial AML/MDS and MonoMac/Emberger syndromes. Genomic excision of the ectopic enhancer restored EVI1 silencing and led to growth inhibition and differentiation of AML cells, which could be replicated by pharmacologic BET-inhibition. Our data show that structural rearrangements involving chromosomal repositioning of enhancers can cause deregulation of two unrelated distal genes, with cancer as the outcome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-01-20T10:51:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000670","title":"Analysis of structural and sequence variations in relapsed childhood high hyperdiploid acute lymphoblastic leukemia by whole genome and whole exome sequencing","description":"High hyperdiploidy (51–67 chromosomes) is the most frequent numerical cytogenetic alteration in pediatric B-cell precursor acute lymphoblastic leukemia (ALL), occurring in 25–30% of patients. It is characterized by nonrandom gains of chromosomes X, 4, 6, 10, 14, 17, 18, or 21.1 In general, children suffering from high hyperdiploid ALL (HH-ALL) have a favorable prognosis, nevertheless 15–20% of cases relapse. High hyperdiploidy arises in utero and requires cooperating oncogenic lesions for the development of acute lymphoblastic leukemia (ALL) and relapse. To ascertain these genetic changes we analyzed structural and sequence variations in six children with recurrent high hyperdiploid ALL (HH-ALL) at diagnosis, remission and/or relapse.","abstract":"High hyperdiploidy (51–67 chromosomes) is the most frequent numerical cytogenetic alteration in pediatric B-cell precursor acute lymphoblastic leukemia (ALL), occurring in 25–30% of patients. It is characterized by nonrandom gains of chromosomes X, 4, 6, 10, 14, 17, 18, or 21.1 In general, children suffering from high hyperdiploid ALL (HH-ALL) have a favorable prognosis, nevertheless 15–20% of cases relapse. High hyperdiploidy arises in utero and requires cooperating oncogenic lesions for the development of acute lymphoblastic leukemia (ALL) and relapse. To ascertain these genetic changes we analyzed structural and sequence variations in six children with recurrent high hyperdiploid ALL (HH-ALL) at diagnosis, remission and/or relapse.","study_type":"Other","pubmed_ids":[23508829],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000671","title":"Whole genome sequencing of Japanese HCCs","description":"To determine somatic mutation profiles and substitution signatures in Japanese HCC, we performed whole genome sequencing of 31 HCCs with various epidemiological backgrounds. Somatic mutations and rearrangements were determined as previously reported. The data will be deposited to the ICGC database and is used for further comparative and integrative analyses.","abstract":"To determine somatic mutation profiles and substitution signatures in Japanese HCC, we performed whole genome sequencing of 31 HCCs with various epidemiological backgrounds. Somatic mutations and rearrangements were determined as previously reported. The data will be deposited to the ICGC database and is used for further comparative and integrative analyses.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-01-21T04:30:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000672","title":"WTCCC2 People of the British Isles (POBI) genotypes","description":"As part of the WTCCC2 project, approximately 2,900 individuals from the People of the British Isles (POBI) project were genotyped on the  Illumina 1.2M array (2,912 samples) and the Affymetrix 6.0 array (2,930 samples).","abstract":"As part of the WTCCC2 project, approximately 2,900 individuals from the People of the British Isles (POBI) project were genotyped on the  Illumina 1.2M array (2,912 samples) and the Affymetrix 6.0 array (2,930 samples).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-01-21T14:53:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000673","title":"Exploration of CNV’s and SNV’s in cancers with well-known genetic rearrangements: Identification of additional genetic changes in rearrangements-driven cancer","description":"Specific cancers are well known to have specific gene rearrangements. Representative cancer is chronic myeloid leukemia (CML) which is famous for BCR/ABL gene rearrangements. By the way, also genetic rearrangements are not infrequently found in acute leukemia, and those include CBFB/MYH11 rearrangements, PML/RARA rearrangements, AML/ETO rearrangements, and BCR/ABL rearrangements. The situation is same is for lung adenocarcinoma of non-smokers and prostate cancers, and ALK and RET gene rearrangements are recently found. However, not all these rearrangements are sufficient to develop cancer, and it is suggested that some genetic aberrations are required for the development and progression of cancer in addition to these genetic rearrangements.   In this study, we have a plan to explore the existence of additional genetic changes including single nucleotide variants (SNV’s) and copy number variations (CNV’s) in cancers with specific genetic rearrangements so as to define additional genetic changes that confer full oncogenic potential to cancer cells.  So as to look at SNV’s and small indels, we are going to use whole exome sequencing (WES) data. And as for CNV’s, we are going to use array-CGH data. Also, to check the functionality of these genetic changes, we are going to use whole transcriptome data (WTS). In addition, in samples with whole genome sequencing (WGS ) data, we are going  to explore genetic changes in intronic regions also.  In fact, we sequenced 10 AML samples which are known to have specific genetic rearrangements. Analysis of these WGS, WES and WTS data are under the way. If we have a chance to access WES, array-CGH and WTS data of other cancer samples with specific genetic rearrangements, we would be able to compare additional genetic changes required for oncogenesis in cancer cells with various genetic rearrangements. We hope this result will enlighten our understanding of cancer genetics further.","abstract":"Specific cancers are well known to have specific gene rearrangements. Representative cancer is chronic myeloid leukemia (CML) which is famous for BCR/ABL gene rearrangements. By the way, also genetic rearrangements are not infrequently found in acute leukemia, and those include CBFB/MYH11 rearrangements, PML/RARA rearrangements, AML/ETO rearrangements, and BCR/ABL rearrangements. The situation is same is for lung adenocarcinoma of non-smokers and prostate cancers, and ALK and RET gene rearrangements are recently found. However, not all these rearrangements are sufficient to develop cancer, and it is suggested that some genetic aberrations are required for the development and progression of cancer in addition to these genetic rearrangements.   In this study, we have a plan to explore the existence of additional genetic changes including single nucleotide variants (SNV’s) and copy number variations (CNV’s) in cancers with specific genetic rearrangements so as to define additional genetic changes that confer full oncogenic potential to cancer cells.  So as to look at SNV’s and small indels, we are going to use whole exome sequencing (WES) data. And as for CNV’s, we are going to use array-CGH data. Also, to check the functionality of these genetic changes, we are going to use whole transcriptome data (WTS). In addition, in samples with whole genome sequencing (WGS ) data, we are going  to explore genetic changes in intronic regions also.  In fact, we sequenced 10 AML samples which are known to have specific genetic rearrangements. Analysis of these WGS, WES and WTS data are under the way. If we have a chance to access WES, array-CGH and WTS data of other cancer samples with specific genetic rearrangements, we would be able to compare additional genetic changes required for oncogenesis in cancer cells with various genetic rearrangements. We hope this result will enlighten our understanding of cancer genetics further.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-01-21T17:06:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000674","title":"High-throughput Detection of Clinically Relevant Mutations in Archived Tumor Samples By Multiplexed PCR and Next Generation Sequencing","description":"PURPOSE: Tailoring cancer treatment to tumor molecular characteristics promises to make personalized medicine a reality. However, reliable genetic profiling of archived clinical specimens has been hindered by limited sensitivity and high false positive rates. Here, we describe a novel methodology, MMP-seq, which enables sensitive and specific high-throughput, high content genetic profiling in archived clinical samples.  EXPERIMENTAL DESIGN: We first validated MMP-seq’s technical performance in 66 cancer cell lines and a Latin square cross-dilution of known somatic mutations. We next characterized the performance of MMP-seq in 17 formalin-fixed paraffin embedded (FFPE) clinical samples using matched fresh frozen (FF) tissue from the same tumors as benchmarks. To demonstrate the potential clinical utility of our methodology, we profiled FFPE tumor samples from 73 endometrial cancer patients.  RESULTS: We demonstrated that MMP-seq enabled rapid and simultaneous profiling of a panel of 88 cancer genes in 48 samples, and detected variants at frequencies as low as 0.4%. We identified DNA degradation and deamination as the main error sources and developed practical and robust strategies for mitigating these issues, and dramatically reduced the false positive rate. Applying MMP-seq to a cohort of endometrial tumor samples identified extensive, potentially actionable alterations in the PI3K and RAS pathways, including novel PIK3R1 hotspot mutations that may disrupt negative regulation of PIK3CA.  CONCLUSIONS: MMP-seq provides a robust solution for comprehensive, reliable and high- throughput genetic profiling of clinical tumor samples, paving the way for the incorporation of genomic-based testing into clinical investigation and practice.","abstract":"PURPOSE: Tailoring cancer treatment to tumor molecular characteristics promises to make personalized medicine a reality. However, reliable genetic profiling of archived clinical specimens has been hindered by limited sensitivity and high false positive rates. Here, we describe a novel methodology, MMP-seq, which enables sensitive and specific high-throughput, high content genetic profiling in archived clinical samples.  EXPERIMENTAL DESIGN: We first validated MMP-seq’s technical performance in 66 cancer cell lines and a Latin square cross-dilution of known somatic mutations. We next characterized the performance of MMP-seq in 17 formalin-fixed paraffin embedded (FFPE) clinical samples using matched fresh frozen (FF) tissue from the same tumors as benchmarks. To demonstrate the potential clinical utility of our methodology, we profiled FFPE tumor samples from 73 endometrial cancer patients.  RESULTS: We demonstrated that MMP-seq enabled rapid and simultaneous profiling of a panel of 88 cancer genes in 48 samples, and detected variants at frequencies as low as 0.4%. We identified DNA degradation and deamination as the main error sources and developed practical and robust strategies for mitigating these issues, and dramatically reduced the false positive rate. Applying MMP-seq to a cohort of endometrial tumor samples identified extensive, potentially actionable alterations in the PI3K and RAS pathways, including novel PIK3R1 hotspot mutations that may disrupt negative regulation of PIK3CA.  CONCLUSIONS: MMP-seq provides a robust solution for comprehensive, reliable and high- throughput genetic profiling of clinical tumor samples, paving the way for the incorporation of genomic-based testing into clinical investigation and practice.","study_type":"Other","pubmed_ids":[24573554],"external_links":null,"is_released":true,"released_date":"2014-01-21T17:56:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000675","title":"Ten pairs of GACA-CN","description":"This study is about ten pairs of GACA-CN","abstract":"This study is about ten pairs of GACA-CN","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000676","title":"Whole exomes sequencing of 10 pairs ccRCC","description":"We sequenced whole exomes of ten pairs of clear cell renal cell  carcinomas (ccRCCs)","abstract":"We sequenced whole exomes of ten pairs of clear cell renal cell  carcinomas (ccRCCs)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000677","title":"Whole exome sequencing of 103 pairs BLCA-CN","description":"We sequenced 50M exomes of 103 pairs bladder cancer of chinese","abstract":"We sequenced 50M exomes of 103 pairs bladder cancer of chinese","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-01-22T12:08:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000678","title":"WGS of liver cancer in the Japanese population","description":"Hepatocellular carcinoma (HCC) is the third leading cancer-related cause of death and the seventh most common form of cancer worldwide, with an estimate of more than 700,000 new cases each year. The most established risk factors of HCC are chronic HBV and HCV infection. HBV infection is responsible for over 50% of the worldwide attributable risk of HCC, especially in East Asia and Africa, while in Japan and several Western countries HCV infection is the most common risk factor for HCC. To gain insights into the molecular alterations of virus-associated HCC, we performed whole genome sequencing (WGS) of 321 HCC tumors from 159 patients. This work was performed as a part of the ICGC (International Cancer Genome Consortium) project.","abstract":"Hepatocellular carcinoma (HCC) is the third leading cancer-related cause of death and the seventh most common form of cancer worldwide, with an estimate of more than 700,000 new cases each year. The most established risk factors of HCC are chronic HBV and HCV infection. HBV infection is responsible for over 50% of the worldwide attributable risk of HCC, especially in East Asia and Africa, while in Japan and several Western countries HCV infection is the most common risk factor for HCC. To gain insights into the molecular alterations of virus-associated HCC, we performed whole genome sequencing (WGS) of 321 HCC tumors from 159 patients. This work was performed as a part of the ICGC (International Cancer Genome Consortium) project.","study_type":"Other","pubmed_ids":[20393554],"external_links":null,"is_released":true,"released_date":"2014-01-23T01:14:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000679","title":"Integrative genomic profiling of hepatocellular adenomas reveals recurrent FRK activating mutations and mutational processes of malignant transformation","description":"Hepatocellular adenomas (HCA) are benign liver tumors predominantly developed in women using oral contraception. Here, exome sequencing identified novel recurrent somatic FRK mutations that induce constitutive kinase activity, STAT3 activation and cell proliferation sensitive to Src inhibitors. We also found new recurrent mutations activating JAK1, gp130 or ß-catenin. Chromosome copy-number and methylation profiling revealed patterns that correlated with specific gene mutations and tumor phenotypes. Finally, integrative analysis of HCA transformed to hepatocellular carcinoma revealed ß-catenin mutation as an early alteration and TERT promoter mutations as associated with the last step of the adenoma-carcinoma transition. In conclusion, we identified the genomic diversity in benign hepatocyte proliferation, new therapeutic targets and the key genomic determinants of the adenoma-carcinoma transformation sequence.  Significance: Malignant transformation of benign adenoma into malignant carcinoma is frequently observed in several epithelial tumor types. Adenoma-carcinoma transition is crucial for the patient prognosis, however, little is known on the molecular mechanisms involved. Here, we performed an integrated genomic analysis of hepatocellular adenomas (HCA). Among several novel gene mutations, we identified recurrent somatic mutation activating FRK, a Src-like kinase. FRK activating mutations induce STAT3 activation and cell proliferation that can be targeted by Src inhibitors. Focusing on malignant transformation of HCA in hepatocellular carcinoma, we identified CTNNB1 and TERT promoter mutation as early and late genomic events involved in adenoma-carcinoma transition. In conclusion, we propose new therapeutic targets and an identification of adenomas with the highest risk of malignant transformation.   Highlights: - FRK is activated by somatic recurrent mutations. - FRK mutants promote cell proliferation sensitive to src inhibitors. - CTNNB1 activation is an early event in HCA transformation. - TERT promoter mutations are associated with adenoma-carcinoma transition.","abstract":"Hepatocellular adenomas (HCA) are benign liver tumors predominantly developed in women using oral contraception. Here, exome sequencing identified novel recurrent somatic FRK mutations that induce constitutive kinase activity, STAT3 activation and cell proliferation sensitive to Src inhibitors. We also found new recurrent mutations activating JAK1, gp130 or ß-catenin. Chromosome copy-number and methylation profiling revealed patterns that correlated with specific gene mutations and tumor phenotypes. Finally, integrative analysis of HCA transformed to hepatocellular carcinoma revealed ß-catenin mutation as an early alteration and TERT promoter mutations as associated with the last step of the adenoma-carcinoma transition. In conclusion, we identified the genomic diversity in benign hepatocyte proliferation, new therapeutic targets and the key genomic determinants of the adenoma-carcinoma transformation sequence.  Significance: Malignant transformation of benign adenoma into malignant carcinoma is frequently observed in several epithelial tumor types. Adenoma-carcinoma transition is crucial for the patient prognosis, however, little is known on the molecular mechanisms involved. Here, we performed an integrated genomic analysis of hepatocellular adenomas (HCA). Among several novel gene mutations, we identified recurrent somatic mutation activating FRK, a Src-like kinase. FRK activating mutations induce STAT3 activation and cell proliferation that can be targeted by Src inhibitors. Focusing on malignant transformation of HCA in hepatocellular carcinoma, we identified CTNNB1 and TERT promoter mutation as early and late genomic events involved in adenoma-carcinoma transition. In conclusion, we propose new therapeutic targets and an identification of adenomas with the highest risk of malignant transformation.   Highlights: - FRK is activated by somatic recurrent mutations. - FRK mutants promote cell proliferation sensitive to src inhibitors. - CTNNB1 activation is an early event in HCA transformation. - TERT promoter mutations are associated with adenoma-carcinoma transition.","study_type":"Other","pubmed_ids":[24735922],"external_links":null,"is_released":true,"released_date":"2014-01-24T10:17:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000680","title":"Molecular Signature of Saudi Thyroid Cancer Using whole exome sequencing","description":"In Saudi Arabia, thyroid cancer ranked second only to breast cancer among females, eleventh among males and this increased incidence is prevalent in other Gulf Council Countries also. Differentiated thyroid cancer, which includes papillary thyroid cancer (PTC) and follicular subtypes, accounts for 90% of all thyroid malignancies. Currently, there are no clinical or molecular diagnostic tools to predict recurrence and aggressiveness of a subset of PTC. With the goal of better understanding the pathobiology of thyroid carcinogenesis we will use Whole Exome Sequencing to decipher the molecular and genetic signature of Saudi PTC based on International Cancer Genome Consortium (ICGC) Guidelines. The study will provide a better understanding of PTC and should have important clinical implications in the development of new and better strategies for targeted therapeutic intervention for the treatment of Saudi Arabian PTC","abstract":"In Saudi Arabia, thyroid cancer ranked second only to breast cancer among females, eleventh among males and this increased incidence is prevalent in other Gulf Council Countries also. Differentiated thyroid cancer, which includes papillary thyroid cancer (PTC) and follicular subtypes, accounts for 90% of all thyroid malignancies. Currently, there are no clinical or molecular diagnostic tools to predict recurrence and aggressiveness of a subset of PTC. With the goal of better understanding the pathobiology of thyroid carcinogenesis we will use Whole Exome Sequencing to decipher the molecular and genetic signature of Saudi PTC based on International Cancer Genome Consortium (ICGC) Guidelines. The study will provide a better understanding of PTC and should have important clinical implications in the development of new and better strategies for targeted therapeutic intervention for the treatment of Saudi Arabian PTC","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-01-24T16:02:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000681","title":"Genome-wide SNP-SNP interactions in COPD","description":"Chronic obstructive pulmonary disease (COPD) is a complex disorder involving multiple genes. However, despite genome-wide association studies (GWAS) identifying several COPD-related genes, we know a significant proportion of the trait’s heritability remains unexplained. We therefore performed the first genome-wide SNP-SNP interaction (epistasis) analysis in COPD, as we suspect epistasis holds the key to at least part of the missing heritability. We used the NELSON cohort as a discovery set, comprising 1,030 cases and 1,808 controls, and the LifeLines cohort as a replication set, with 711 cases and 3,013 controls. Our results show SNP-SNP interactions suggesting that cell adhesion and cell communication pathways could be involved in COPD development. SNPs involved in these interactions are annotated to genes that include SERPINB9, CNTN5, PTPRM and SIGLEC1, and which, except for CNTN5, were not previously associated with COPD. Our findings may open up new avenues towards understanding pathways underlying COPD. However, since genome-wide significance was not reached, we should interpret these findings with caution and further replication is needed to confirm our findings.","abstract":"Chronic obstructive pulmonary disease (COPD) is a complex disorder involving multiple genes. However, despite genome-wide association studies (GWAS) identifying several COPD-related genes, we know a significant proportion of the trait’s heritability remains unexplained. We therefore performed the first genome-wide SNP-SNP interaction (epistasis) analysis in COPD, as we suspect epistasis holds the key to at least part of the missing heritability. We used the NELSON cohort as a discovery set, comprising 1,030 cases and 1,808 controls, and the LifeLines cohort as a replication set, with 711 cases and 3,013 controls. Our results show SNP-SNP interactions suggesting that cell adhesion and cell communication pathways could be involved in COPD development. SNPs involved in these interactions are annotated to genes that include SERPINB9, CNTN5, PTPRM and SIGLEC1, and which, except for CNTN5, were not previously associated with COPD. Our findings may open up new avenues towards understanding pathways underlying COPD. However, since genome-wide significance was not reached, we should interpret these findings with caution and further replication is needed to confirm our findings.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000682","title":"Epigenetic Intratumor Heterogeneity and Clonal Evolution in Aggressive Prostate Cancer","description":"Our study investigated the spatial epigenome variation within 5 aggressive prostate adenocarcinomas.","abstract":"Our study investigated the spatial epigenome variation within 5 aggressive prostate adenocarcinomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-01-27T09:12:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000683","title":"Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel","description":"Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel","abstract":"Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000684","title":"Novel genomic structural variations in relapsed childhood ETV6/RUNX1 (TEL/AML1) acute lymphoblastic leukemias identified by next generation sequencing","description":"The chimeric fusion gene ETV6/RUNX1 generated by the interchromosomal translocation t(12;21) presents the most frequent chromosomal aberration in childhood acute lymphoblastic leukemia (ALL), occurring in approximately 25% of all patients. This ALL subtype is associated with an overall favorable prognosis, nevertheless 10-20% of children will suffer from relapse. ETV6/RUNX1-positive preleukemic clones arise already in utero, but require additional cooperating oncogenic lesions for the development of overt leukemia. The aim of the study was to identify assisting genetic alterations and to provide closer insights into the mechanisms driving the development of leukemia and recurrent disease. To this end, whole genome and whole exome sequencing was applied to comprehensively analyze the assisting oncogenic alterations in pediatric patients with initial and/or recurrent ETV6/RUNX1+ ALL (primary disease n=11, recurrent disease m=7). Matched sample sets taken at initial diagnosis, remission and relapse were compared. Mate pair and/or paired end sequencing was carried out for whole genome analysis with inserts spanning 2 kb or 500 kb, respectively. Constructed libraries were sequenced from both ends with 36- or 50-bp reads on a Genome Analyzer IIx or a HiSeq 2000 (Illumina/Solexa), respectively. Reads were aligned against the human reference genome (GRCh37) using the Burrows-Wheeler Alignment tool.","abstract":"The chimeric fusion gene ETV6/RUNX1 generated by the interchromosomal translocation t(12;21) presents the most frequent chromosomal aberration in childhood acute lymphoblastic leukemia (ALL), occurring in approximately 25% of all patients. This ALL subtype is associated with an overall favorable prognosis, nevertheless 10-20% of children will suffer from relapse. ETV6/RUNX1-positive preleukemic clones arise already in utero, but require additional cooperating oncogenic lesions for the development of overt leukemia. The aim of the study was to identify assisting genetic alterations and to provide closer insights into the mechanisms driving the development of leukemia and recurrent disease. To this end, whole genome and whole exome sequencing was applied to comprehensively analyze the assisting oncogenic alterations in pediatric patients with initial and/or recurrent ETV6/RUNX1+ ALL (primary disease n=11, recurrent disease m=7). Matched sample sets taken at initial diagnosis, remission and relapse were compared. Mate pair and/or paired end sequencing was carried out for whole genome analysis with inserts spanning 2 kb or 500 kb, respectively. Constructed libraries were sequenced from both ends with 36- or 50-bp reads on a Genome Analyzer IIx or a HiSeq 2000 (Illumina/Solexa), respectively. Reads were aligned against the human reference genome (GRCh37) using the Burrows-Wheeler Alignment tool.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000685","title":"Recurrent epimutations activate gene body promoters in primary glioblastoma","description":"Aberrant DNA hypomethylation may play an important role in the growth rate of glioblastoma (GBM), but the functional impact on transcription remains poorly understood. We assayed the GBM methylome with MeDIP-seq and MRE-seq, adjusting for copy number differences, in a small set of non-glioma CpG island methylator phenotype (non-G-CIMP) primary tumors. Recurrent hypomethylated loci were enriched within a region of chromosome 5p15 that is specified as a cancer amplicon and also encompasses TERT, encoding telomerase reverse transcriptase, which plays a critical role in tumorigenesis. Overall, 76 gene body promoters were recurrently hypomethylated, including TERT and the oncogenes GLI3 and TP73. Recurring hypomethylation also affected previously unannotated alternative promoters, and luciferase reporter assays for three of four of these promoters confirmed strong promoter activity in GBM cells. Histone H3 lysine 4 trimethylation (H3K4me3) ChIP-seq on tissue from the GBMs uncovered peaks that coincide precisely with tumor-specific decrease of DNA methylation at 200 loci, 133 of which are in gene bodies. Detailed investigation of TP73 and TERT gene body hypomethylation demonstrated increased expression of corresponding alternate transcripts, which in TP73 encodes a truncated p73 protein with oncogenic function and in TERT encodes a putative reverse transcriptase-null protein. Our findings suggest that recurring gene body promoter hypomethylation events, along with histone H3K4 trimethylation, alter the transcriptional landscape of GBM through the activation of a limited number of normally silenced promoters within gene bodies, in at least one case leading to expression of an oncogenic protein.","abstract":"Aberrant DNA hypomethylation may play an important role in the growth rate of glioblastoma (GBM), but the functional impact on transcription remains poorly understood. We assayed the GBM methylome with MeDIP-seq and MRE-seq, adjusting for copy number differences, in a small set of non-glioma CpG island methylator phenotype (non-G-CIMP) primary tumors. Recurrent hypomethylated loci were enriched within a region of chromosome 5p15 that is specified as a cancer amplicon and also encompasses TERT, encoding telomerase reverse transcriptase, which plays a critical role in tumorigenesis. Overall, 76 gene body promoters were recurrently hypomethylated, including TERT and the oncogenes GLI3 and TP73. Recurring hypomethylation also affected previously unannotated alternative promoters, and luciferase reporter assays for three of four of these promoters confirmed strong promoter activity in GBM cells. Histone H3 lysine 4 trimethylation (H3K4me3) ChIP-seq on tissue from the GBMs uncovered peaks that coincide precisely with tumor-specific decrease of DNA methylation at 200 loci, 133 of which are in gene bodies. Detailed investigation of TP73 and TERT gene body hypomethylation demonstrated increased expression of corresponding alternate transcripts, which in TP73 encodes a truncated p73 protein with oncogenic function and in TERT encodes a putative reverse transcriptase-null protein. Our findings suggest that recurring gene body promoter hypomethylation events, along with histone H3K4 trimethylation, alter the transcriptional landscape of GBM through the activation of a limited number of normally silenced promoters within gene bodies, in at least one case leading to expression of an oncogenic protein.","study_type":"Other","pubmed_ids":[24709822],"external_links":null,"is_released":true,"released_date":"2014-01-28T19:49:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000686","title":"DDD_WGS","description":"This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Thousands of babies are born each year in the UK who fail to develop normally because of errors in their genetic makeup. Currently, diagnosis is restricted to a small minority of children and requires the clinician to recognise the appearance of the child and the pattern of symptoms, supplemented by the use of microscopes to identify large rearrangements of the genetic material in chromosomes. Research shows that the latest molecular testing methods identify previously undetectable changes in chromosomes allowing new diagnoses to be made. However, clinical use is hampered by the limited availability and inconsistent application of these technologies, and by lack of basic knowledge to link genetic changes directly to symptoms. The consequence is that clinical diagnoses remain impossible except for a small number of children.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000687","title":"Illumina Human OmniExpress genotyping data from the Cretan Greek isolate collection HELIC MANOLIS","description":"Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies. Here we have genotyped individuals from a Greek population isolate on the Illumina Human OmniExpress BeadChip array. The HELIC (Hellenic Isolated Cohorts) MANOLIS (Minoan Isolates) collection focuses on Anogia and surrounding Mylopotamos villages. Recruitment of this population-based sample was primarily carried out at the village medical centres. All individuals were older than 17 years and had to have at least one parent from the Mylopotamos area. www.helic.org  **The data may not be used for population genetics analyses**","abstract":"Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies. Here we have genotyped individuals from a Greek population isolate on the Illumina Human OmniExpress BeadChip array. The HELIC (Hellenic Isolated Cohorts) MANOLIS (Minoan Isolates) collection focuses on Anogia and surrounding Mylopotamos villages. Recruitment of this population-based sample was primarily carried out at the village medical centres. All individuals were older than 17 years and had to have at least one parent from the Mylopotamos area. www.helic.org  **The data may not be used for population genetics analyses**","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-01-29T12:00:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000688","title":"Illumina Human OmniExpress genotype data from the Pomak villages in Greece (HELIC Pomak Isolates)","description":"Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies. Here we have genotyped individuals from a Greek population isolate on the Illumina Human OmniExpress BeadChip array. The HELIC (Hellenic Isolated Cohorts) Pomak collection focuses on the Pomak villages in Greece. Recruitment of this population-based sample was primarily carried out at the village medical centres. www.helic.org","abstract":"Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies. Here we have genotyped individuals from a Greek population isolate on the Illumina Human OmniExpress BeadChip array. The HELIC (Hellenic Isolated Cohorts) Pomak collection focuses on the Pomak villages in Greece. Recruitment of this population-based sample was primarily carried out at the village medical centres. www.helic.org","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000689","title":"BLUEPRINT EpiVar Whole Genome Sequencing","description":"BLUEPRINT EpiVar Whole Genome Sequencing","abstract":"BLUEPRINT EpiVar Whole Genome Sequencing","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-01-30T15:06:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000690","title":"Structural and sequence variations associated with germline ATM and NBS1 mutations analyzed by whole-genome and whole-exome sequencing","description":"Germline mutations in the DNA repair genes ataxia teleangiectasia mutated (ATM) and nijmegen breakage syndrome 1 (NBS1) are associated with chromosomal instability. Children bearing ATM or NBS1 mutations have an increased risk of developing lymphoma and leukemia. Due to inefficient DNA repair the treatment of these malignancies is hampered by therapy-associated toxicity. The incidence of secondary tumors is high. The impact of these mutations on structural and sequence variations were analyzed by whole genome and whole exome sequencing employing matched sample sets of tumor and remission blood samples derived from children with ATM (n=4) or NBS1 mutations (n=3) suffering from lymphoma (n=6) or leukemia (n=1).","abstract":"Germline mutations in the DNA repair genes ataxia teleangiectasia mutated (ATM) and nijmegen breakage syndrome 1 (NBS1) are associated with chromosomal instability. Children bearing ATM or NBS1 mutations have an increased risk of developing lymphoma and leukemia. Due to inefficient DNA repair the treatment of these malignancies is hampered by therapy-associated toxicity. The incidence of secondary tumors is high. The impact of these mutations on structural and sequence variations were analyzed by whole genome and whole exome sequencing employing matched sample sets of tumor and remission blood samples derived from children with ATM (n=4) or NBS1 mutations (n=3) suffering from lymphoma (n=6) or leukemia (n=1).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000691","title":"miRNA_expression_in_response_to_LPS_stimulus_in_macrophages","description":"Our lab is currently using macrophages as a model system for understanding how geneticvariation modulates the response to external environmental stimulus. We want to extend thisbeyond regular polyadenylated RNA to small RNAs such as miRNAs. This project wouldcover the costs of a pilot to study miRNA response to LPS stimulus, and will be performed aspart of a rotation project in the lab. We will require a small number of miRNA libraries and asingle lane of MiSeq","abstract":"Our lab is currently using macrophages as a model system for understanding how geneticvariation modulates the response to external environmental stimulus. We want to extend thisbeyond regular polyadenylated RNA to small RNAs such as miRNAs. This project wouldcover the costs of a pilot to study miRNA response to LPS stimulus, and will be performed aspart of a rotation project in the lab. We will require a small number of miRNA libraries and a single lane of MiSeq","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-02-05T12:50:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000692","title":"FFPE_CPA_Accreditation_Study__Part_2","description":"FFPE CPA accreditation of genome-scale sequencing in routinely collected formalin-fixed paraffin-embedded (FFPE) cancer specimens versus matched fresh-frozen samples using targeted pulldown capture prior to Illumina sequencing.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of cancer genomes to find somatic mutations on a massive scale. Being able to follow up studies in a larger cohort from FFPE samples would greatly increase the capacity of these studies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-02-05T16:02:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000693","title":"Neuromics / RD-Connect - congenital myasthenic syndrome","description":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with a congenital myasthenic syndrome phenotype and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","abstract":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with a congenital myasthenic syndrome phenotype and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000694","title":"Neuromics / RD-Connect - ataxia","description":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with an ataxia phenotype, in particular spinocerebellar ataxia, and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","abstract":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with an ataxia phenotype, in particular spinocerebellar ataxia, and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000695","title":"Neuromics / RD-Connect - frontotemporal dementia","description":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with a frontotemporal dementia phenotype, and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","abstract":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with a frontotemporal dementia phenotype, and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000696","title":"Neuromics / RD-Connect - hereditary motor neuropathy","description":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with a hereditary motor neuropathy phenotype, and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","abstract":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with a hereditary motor neuropathy phenotype, and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000697","title":"Neuromics / RD-Connect - hereditary spastic paraplegia","description":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with a hereditary spastic paraplegia phenotype, and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","abstract":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with a hereditary spastic paraplegia phenotype, and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000698","title":"Neuromics / RD-Connect - Huntington's disease","description":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with a Huntington's disease phenotype and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","abstract":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with a Huntington's disease phenotype and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-02-06T22:55:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000699","title":"Neuromics / RD-Connect - muscular channelopathy","description":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with a muscular channelopathy phenotype and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","abstract":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with a muscular channelopathy phenotype and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000700","title":"Neuromics / RD-Connect - muscular dystrophy","description":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with a muscular dystrophy phenotype and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","abstract":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with a muscular dystrophy phenotype and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000701","title":"Neuromics / RD-Connect - spinal muscular atrophy / lower motor neuron disease","description":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with a spinal muscular atrophy or lower motor neuron disease phenotype and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","abstract":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with a spinal muscular atrophy or lower motor neuron disease phenotype and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000702","title":"Neuromics / RD-Connect - congenital muscular dystrophy / congenital myopathy","description":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with a congenital muscular dystrophy or congenital myopathy phenotype and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","abstract":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders.   Data includes BAM and VCF files from whole-exome sequencing and standardised phenotypic data mapped to the human phenotype ontology (HPO). In some cases proteomic, transcriptomic and metabolomic data may also be available.  This study groups together datasets from individuals with a congenital muscular dystrophy or congenital myopathy phenotype and also includes some unaffected family members. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000703","title":"MDS_Sequential_Treatment_Validation","description":"Validations of variants identified by exome sequencing in sequential samples derived after treatment cycle with AZA.","abstract":"Validations of variants identified by exome sequencing in sequential samples derived after treatment cycle with AZA.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-02-07T12:22:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000704","title":"Metastatic_breast_cancer_targeted_gene_screen","description":"The samples will be sequenced for a targeted panel of cancer relevant genes (n ~ 370) and analysed for somatic mutations.","abstract":"The sample series consists of primary tumors as well as multiple metastatic lesions harvested from different timepoints through the course of the disease for 206 patients suffering from metastatic breast cancer.The aim of the study is to use this samples set to assess the selection of subclones of cancer cells over time, and to pinpoint the mutations that are selected for during a tumours progression towards multidrug resistance.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-02-07T12:27:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000705","title":"Targeted_pulldown_DNA_methylation_study","description":"To analyse mC and hmC profiles in regions of interest, we are setting up protocols combining Illumina SureSelect Methyl-Seq Target Enrichment System and CRGX TrueMethyl Kit. This is the first pilot sequencing.","abstract":"This Study aims analysis of the mC and hmC levels from genomic regions of interest. To set up protocols, we combined Illumina SureSelect Methyl-Seq Target Enrcihment System adn CEGX TrueMethyl Kit. Bisulfite- and oxBisulfite- treated DNA libraries were constructed from K562 cell line DNA","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000706","title":"Whole-Genome sequencing of hepatocellular carcinomas","description":"The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer).  The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors using whole genome and whole exome sequencing together with CGH-SNP, methylome and transcriptomic profiling. For this purpose, a series of 500 liver tumors are collected through the French National Liver Collection and these samples will be analyzed using the different omics technologies. The data will be deposited in the ICGC and EGA database to be publically available for the scientific community.  Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem. It is the 3rd cause of cancer-related mortality. Advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. Thus, the development of next-generation sequencing technologies has made it possible to generate more comprehensive catalogues of somatic alteration events (single nucleotide substitutions, structural variations, and epigenetic changes) in liver cancer genome than ever before. The dataset will include 50 whole genome sequencing tumor/germline pairs, of which 6 are deposited in February 2014.","abstract":"The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer).  The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors using whole genome and whole exome sequencing together with CGH-SNP, methylome and transcriptomic profiling. For this purpose, a series of 500 liver tumors are collected through the French National Liver Collection and these samples will be analyzed using the different omics technologies. The data will be deposited in the ICGC and EGA database to be publically available for the scientific community.  Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem. It is the 3rd cause of cancer-related mortality. Advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. Thus, the development of next-generation sequencing technologies has made it possible to generate more comprehensive catalogues of somatic alteration events (single nucleotide substitutions, structural variations, and epigenetic changes) in liver cancer genome than ever before. The dataset will include 50 whole genome sequencing tumor/germline pairs, of which 6 are deposited in February 2014.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-02-18T13:31:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000707","title":"BASIS_RNAseq","description":"We propose to definitively characterise the somatic genetics of ER+ve, HER2-ve breast cancer through generation of comprehensive catalogues of somatic mutations in 500 cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-02-18T13:53:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000708","title":"Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors","description":"Large-cell neuroendocrine lung carcinomas (LCNEC) have similarities with other lung cancers, but their precise relationship has remained unclear. We conducted comprehensive genomic (n=60) and transcriptomic (n=69) analyses of 75 LCNECs and identified two molecular subgroups: “type I LCNECs” with bi-allelic TP53 and STK11/KEAP1 alterations (37%), and “type II LCNECs” enriched for bi-allelic inactivation of TP53 and RB1 (42%). Despite sharing genomic alterations with adenocarcinomas and squamous cell carcinomas, no transcriptional relationship was found; instead LCNECs form distinct transcriptional subgroups with closest similarity to SCLC. While type I LCNECs and SCLCs exhibit a neuroendocrine profile with ASCL1high/DLL3high/NOTCHlow, type II LCNECs bear TP53 and RB1 alterations and differ from most SCLC tumors with reduced neuroendocrine markers, a pattern of ASCL1low/DLL3low/NOTCHhigh and upregulation of immune-related pathways. In conclusion, LCNECs are comprised of two molecularly defined subgroups, and distinguishing them from SCLC may allow for stratified targeted treatments for high-grade neuroendocrine lung tumors.","abstract":"Large-cell neuroendocrine lung carcinomas (LCNEC) have similarities with other lung cancers, but their precise relationship has remained unclear. We conducted comprehensive genomic (n=60) and transcriptomic (n=69) analyses of 75 LCNECs and identified two molecular subgroups: “type I LCNECs” with bi-allelic TP53 and STK11/KEAP1 alterations (37%), and “type II LCNECs” enriched for bi-allelic inactivation of TP53 and RB1 (42%). Despite sharing genomic alterations with adenocarcinomas and squamous cell carcinomas, no transcriptional relationship was found; instead LCNECs form distinct transcriptional subgroups with closest similarity to SCLC. While type I LCNECs and SCLCs exhibit a neuroendocrine profile with ASCL1high/DLL3high/NOTCHlow, type II LCNECs bear TP53 and RB1 alterations and differ from most SCLC tumors with reduced neuroendocrine markers, a pattern of ASCL1low/DLL3low/NOTCHhigh and upregulation of immune-related pathways. In conclusion, LCNECs are comprised of two molecularly defined subgroups, and distinguishing them from SCLC may allow for stratified targeted treatments for high-grade neuroendocrine lung tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-02-19T12:28:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000709","title":"whole-genome sequencing in 17 ESCC cases and whole-exome sequencing in 71 cases","description":"Esophageal cancer is one of the most aggressive cancers and the sixth leading cause of cancer death worldwide1. Approximately 70% of the global esophageal cancers occur in China and over 90% histopathological forms of this disease are esophageal squamous cell carcinoma (ESCC)2-3. Currently, there are limited clinical approaches for early diagnosis and treatment for ESCC, resulting in a 10% 5-year survival rate for the patients. Meanwhile, the full repertoire of genomic events leading to the pathogenesis of ESCC remains unclear. Here we show a comprehensive genomic analysis in 158 ESCC cases, as part of the International Cancer Genome Consortium (ICGC) Research Projects (http://icgc.org/icgc/cgp/72/371/1001734). We conducted whole-genome sequencing in 17 ESCC cases and whole-exome sequencing in 71 cases, of which 53 cases and additional 70 ESCC cases were subjected to array comparative genomic hybridization (a-CGH) analysis.","abstract":"Esophageal cancer is one of the most aggressive cancers and the sixth leading cause of cancer death worldwide1. Approximately 70% of the global esophageal cancers occur in China and over 90% histopathological forms of this disease are esophageal squamous cell carcinoma (ESCC)2-3. Currently, there are limited clinical approaches for early diagnosis and treatment for ESCC, resulting in a 10% 5-year survival rate for the patients. Meanwhile, the full repertoire of genomic events leading to the pathogenesis of ESCC remains unclear. Here we show a comprehensive genomic analysis in 158 ESCC cases, as part of the International Cancer Genome Consortium (ICGC) Research Projects (http://icgc.org/icgc/cgp/72/371/1001734). We conducted whole-genome sequencing in 17 ESCC cases and whole-exome sequencing in 71 cases, of which 53 cases and additional 70 ESCC cases were subjected to array comparative genomic hybridization (a-CGH) analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-02-20T01:56:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000710","title":"103 pairs of BLCA-CN","description":"We sequenced 103 pairs of BLCA-CN","abstract":"We sequenced 103 pairs of BLCA-CN","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000711","title":"Identification_of_cardiovascular_biomarkers_through_an_integrative_omics_approach","description":"Recent GWAS studies have made extensive use of large eQTL data sets to functionallyannotate index SNPs. With a large number of association signals located outside codingregions there has been an intense search among sequence variants affecting geneexpression at the transcriptional level. However, little progress has been made in mappingregulatory variants that affect protein levels at the translational or post-translational level. It isnow possible to undertake a protein QTL scan for focused sets of e.g. oxidized proteins bymass spectrometry. We have established a collaboration with a longitudinal, family-basedstudy in France, the Stanislas cohort, which comprises circa 1000 nuclear families (4,295individuals) and has follow up data for 10 years (three visits). We have undertaken a pilotstudy in a focus set of 257 subjects from 79 families with the aim to integrate GWAS,transcriptomic and DNA methylation data with proteomic data on a set of 100 proteinsmeasured in PBMCs. We have already generated GWAS data using Illumina's core-exomechip as well as DNA methylation profiles with the 450K array. We propose to use RNA seq togenerate transcriptomic data of the corresponding PBMCs.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Recent GWAS studies have made extensive use of large eQTL data sets to functionallyannotate index SNPs. With a large number of association signals located outside codingregions there has been an intense search among sequence variants affecting geneexpression at the transcriptional level. However, little progress has been made in mappingregulatory variants that affect protein levels at the translational or post-translational level. It isnow possible to undertake a protein QTL scan for focused sets of e.g. oxidized proteins bymass spectrometry. We have established a collaboration with a longitudinal, family-basedstudy in France, the Stanislas cohort, which comprises circa 1000 nuclear families (4,295individuals) and has follow up data for 10 years (three visits). We have undertaken a pilotstudy in a focus set of 257 subjects from 79 families with the aim to integrate GWAS,transcriptomic and DNA methylation data with proteomic data on a set of 100 proteinsmeasured in PBMCs. We have already generated GWAS data using Illumina's core-exomechip as well as DNA methylation profiles with the 450K array. We propose to use RNA seq togenerate transcriptomic data of the corresponding PBMCs.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-02-25T14:50:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000712","title":"Whole exome sequencing of 49 tumor-blood pairs and transcriptome sequencing of 44 tumors for adrenocortical tumors","description":"Adrenal Cushing syndrome, which leads to type 2 diabetes, obesity and hypertension, is caused by ACTH-independent production of glucocorticoid by adrenocortical tumors. To investigate the genetic origins of cortisol-producing adrenocortical tumors, we performed whole exome sequencing of 49 tumor-blood pairs and transcriptome sequencing of 44 tumors","abstract":"Adrenal Cushing syndrome, which leads to type 2 diabetes, obesity and hypertension, is caused by ACTH-independent production of glucocorticoid by adrenocortical tumors. To investigate the genetic origins of cortisol-producing adrenocortical tumors, we performed whole exome sequencing of 49 tumor-blood pairs and transcriptome sequencing of 44 tumors","study_type":"Other","pubmed_ids":[24700472],"external_links":null,"is_released":true,"released_date":"2014-02-26T03:38:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000713","title":"UK10K COHORT IMPUTATION","description":"Imputation panel created from UK10K_COHORT_ALSPAC (EGAD00001000740) and UK10K_COHORT_TWINSUK (EGAD00001000741) datasets.","abstract":"Imputation panel created from UK10K_COHORT_ALSPAC (EGAD00001000740) and UK10K_COHORT_TWINSUK (EGAD00001000741) datasets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-02-26T11:36:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000714","title":"Small cell carcinoma of the ovary, hypercalcemic type, displays frequent inactivating germline and somatic mutations in SMARCA4","description":"Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is an extremely rare, aggressive cancer affecting children and young women. We identified germline and somatic inactivating mutations in the SWI/SNF chromatin-remodeling gene SMARCA4 in 75% (9/12) of SCCOHT patients in addition to SMARCA4 protein loss in 82% (14/17) of SCCOHT tumors, but in only 0.4% (2/485) of other primary ovarian tumors. These data implicate SMARCA4 in SCCOHT oncogenesis.","abstract":"Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is an extremely rare, aggressive cancer affecting children and young women. We identified germline and somatic inactivating mutations in the SWI/SNF chromatin-remodeling gene SMARCA4 in 75% (9/12) of SCCOHT patients in addition to SMARCA4 protein loss in 82% (14/17) of SCCOHT tumors, but in only 0.4% (2/485) of other primary ovarian tumors. These data implicate SMARCA4 in SCCOHT oncogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-02-28T01:06:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000715","title":"Small cell carcinoma of the ovary, hypercalcemic type, displays frequent inactivating germline and somatic mutations in SMARCA4","description":"Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is an extremely rare, aggressive cancer affecting children and young women. We identified germline and somatic inactivating mutations in the SWI/SNF chromatin-remodeling gene SMARCA4 in 75% (9/12) of SCCOHT patients in addition to SMARCA4 protein loss in 82% (14/17) of SCCOHT tumors, but in only 0.4% (2/485) of other primary ovarian tumors. These data implicate SMARCA4 in SCCOHT oncogenesis.","abstract":"Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is an extremely rare, aggressive cancer affecting children and young women. We identified germline and somatic inactivating mutations in the SWI/SNF chromatin-remodeling gene SMARCA4 in 75% (9/12) of SCCOHT patients in addition to SMARCA4 protein loss in 82% (14/17) of SCCOHT tumors, but in only 0.4% (2/485) of other primary ovarian tumors. These data implicate SMARCA4 in SCCOHT oncogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000716","title":"Myelodysplastic cells in patients re-program mesenchymal stromal cells to establish a transplantable stem cell-niche disease unit.","description":"Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms with defects in hematopoietic stem/progenitor cells (HSPCs) and possibly the HSPC niche. Here we show that patient-derived mesenchymal stromal cells (MDS MSCs) display a disturbed differentiation program and are essential for the propagation of MDS-initiating lin-CD34+CD38- stem cells in orthotopic xenografts. Overproduction of niche factors such as N-Cadherin, IGFBP2, VEGFA and LIF is associated with the ability of MDS MSCs to enhance MDS expansion. These factors represent putative therapeutic targets to disrupt critical hematopoietic-stromal interactions in MDS. Finally, healthy MSCs adopt \"MDS-MSC like\" molecular features when exposed to hematopoietic MDS cells, indicative of an instructive remodeling of their microenvironment. This patient-derived xenograft model therefore provides functional and molecular evidence that MDS is a complex disease involving both the hematopoietic and stromal compartments. The resulting deregulated expression of niche factors may well also be a feature of other hematopoietic malignancies.","abstract":"Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms with defects in hematopoietic stem/progenitor cells (HSPCs) and possibly the HSPC niche. Here we show that patient-derived mesenchymal stromal cells (MDS MSCs) display a disturbed differentiation program and are essential for the propagation of MDS-initiating lin-CD34+CD38- stem cells in orthotopic xenografts. Overproduction of niche factors such as N-Cadherin, IGFBP2, VEGFA and LIF is associated with the ability of MDS MSCs to enhance MDS expansion. These factors represent putative therapeutic targets to disrupt critical hematopoietic-stromal interactions in MDS. Finally, healthy MSCs adopt \"MDS-MSC like\" molecular features when exposed to hematopoietic MDS cells, indicative of an instructive remodeling of their microenvironment. This patient-derived xenograft model therefore provides functional and molecular evidence that MDS is a complex disease involving both the hematopoietic and stromal compartments. The resulting deregulated expression of niche factors may well also be a feature of other hematopoietic malignancies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-02-28T14:34:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000717","title":"Autozygosity_pilot___QMUL","description":"The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry.  In the UK there are large populations with very high first cousin marriage rates of 20-50%.  Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations.  This pilot study based on existing British-Pakistani cohort samples will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed.  The data deposited in the EGA consists of low coverage whole exome sequencing on these samples.","abstract":"The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry.  In the UK there are large populations with very high first cousin marriage rates of 20-50%.  Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations.  This pilot study based on existing British-Pakistani cohort samples will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed.  The data deposited in the EGA consists of low coverage whole exome sequencing on these samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-05T15:52:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000718","title":"Human_Evolution_3B","description":"The mtDNA and Y chromosome of up to 15 Australian Aborigines,  concentrating on individuals with indigenous lineages will be sequenced using the standard whole-genome sequencing followed by filtering out autosomal and X sequences, so that only mtDNA and the Y chromosome would be analysed and released.","abstract":"According to current models of human expansion out of Africa around 60,000 years ago, there was an early divergence between the ancestors of Australian Aborigines on the one hand and the ancestors of Asians, Europeans and most other non-Africans on the other. Australian Aborigines are therefore of particular importance for understanding these early events, and the subsequent history of this branch of humanity. The project will sequence the mtDNA and Y chromosome of up to 15 Australian Aborigines,  concentrating on individuals with indigenous lineages to address these questions.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-05T16:02:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000719","title":"Evolutionary origin and methylation status of human intronic CpG islands that are not present in mouse","description":"Imprinting of the human RB1 gene is due to the presence of a differentially methylated CpG island (CGI) in intron 2, which is part of a retrogene derived from the PPP1R26 gene on chromosome 9. The murine Rb1 gene does not have this retrogene and is not imprinted. We have investigated whether the RB1/Rb1 locus is unique with respect to these differences. For this we have compared the CGIs from human and mouse by in silico analyses and found out that there are at least 2033 human intronic CGIs that are not present in the mouse. Among these CGIs, 104 show sequences similarities elsewhere in the human genome, which suggests that they arose by retrotransposition. We could narrow down the time points when most of these CGIs appeared during evolution. Their methylation status was analysed in two monocyte methylome datasets from whole genome bisulfite sequencing and in 18 published methylomes. Five CGIs appear to be differentially methylated, which suggests that they are subject of genomic imprinting. They are located in introns of the following genes: RB1, ASRGL1, PARP11, PDXDC1 and MYO1D. Four of these CGIs are parts of retrogenes. Our study supports the notion that imprinting builds on host defence mechanisms by which the genome protects itself against retrotransposed and foreign DNA and that the epigenetic fate of the retrotransposed DNA depends on selective forces at the integration site.","abstract":"Imprinting of the human RB1 gene is due to the presence of a differentially methylated CpG island (CGI) in intron 2, which is part of a retrogene derived from the PPP1R26 gene on chromosome 9. The murine Rb1 gene does not have this retrogene and is not imprinted. We have investigated whether the RB1/Rb1 locus is unique with respect to these differences. For this we have compared the CGIs from human and mouse by in silico analyses and found out that there are at least 2033 human intronic CGIs that are not present in the mouse. Among these CGIs, 104 show sequences similarities elsewhere in the human genome, which suggests that they arose by retrotransposition. We could narrow down the time points when most of these CGIs appeared during evolution. Their methylation status was analysed in two monocyte methylome datasets from whole genome bisulfite sequencing and in 18 published methylomes. Five CGIs appear to be differentially methylated, which suggests that they are subject of genomic imprinting. They are located in introns of the following genes: RB1, ASRGL1, PARP11, PDXDC1 and MYO1D. Four of these CGIs are parts of retrogenes. Our study supports the notion that imprinting builds on host defence mechanisms by which the genome protects itself against retrotransposed and foreign DNA and that the epigenetic fate of the retrotransposed DNA depends on selective forces at the integration site.","study_type":"Other","pubmed_ids":[24923327],"external_links":null,"is_released":true,"released_date":"2014-03-06T13:13:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000720","title":"Location specific ACVR1, FGFR1 and TP53 mutations in pediatric glioblastomas in conjunction with H3.3 K27M.","description":"Recurrent  somatic H3 K27M mutations characterize midline pediatric high-grade astrocytomas (pHGAs). In 40 treatment-naïve midline pHGAs we find additional somatic mutations specific to tumor location. Gain-of-function mutations in ACVR1 occur in tumors of the pons in conjunction with H3.1K27M, while FGFR1 mutations/fusions occur in thalamic tumors in conjunction with H3.3 K27M. Genetic profiles of pHGA show actionable targets, suggesting that pre-treatment biopsy could effectively orient therapeutic efforts.","abstract":"Recurrent  somatic H3 K27M mutations characterize midline pediatric high-grade astrocytomas (pHGAs). In 40 treatment-naïve midline pHGAs we find additional somatic mutations specific to tumor location. Gain-of-function mutations in ACVR1 occur in tumors of the pons in conjunction with H3.1K27M, while FGFR1 mutations/fusions occur in thalamic tumors in conjunction with H3.3 K27M. Genetic profiles of pHGA show actionable targets, suggesting that pre-treatment biopsy could effectively orient therapeutic efforts.","study_type":"Other","pubmed_ids":[24705250],"external_links":null,"is_released":true,"released_date":"2014-03-06T14:03:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000721","title":"Germline and somatic SMARCA4 mutations characterize small-cell carcinoma of the ovary, hypercalcemic type.","description":"Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is the most common undifferentiated ovarian malignancy in women under 40 years1. We sequenced the exomes of six individuals from three SCCOHT families. After discovering segregating deleterious germline mutations in SMARCA4 in all three families, we tested DNA from a fourth family, which also possessed a segregating SMARCA4 germline mutation. All familial tumors sequenced harboured either a somatic mutation or loss of the wild-type allele. Immunohistochemical (IHC) analysis of these and additional familial and non-familial cases showed loss of the SMARCA4 protein (BRG1) in 38/40 tumors overall. Sequencing of cases with available DNA revealed at least one germline or somatic deleterious SMARCA4 mutation in 30/32 cases. Additionally, the SCCOHT cell line BIN-67 contained bi-allelic deleterious mutations in SMARCA4. Our findings identify alterations in SMARCA4 as the major cause of SCCOHT, which could lead to genetic counseling and new treatment approaches.","abstract":"Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is the most common undifferentiated ovarian malignancy in women under 40 years1. We sequenced the exomes of six individuals from three SCCOHT families. After discovering segregating deleterious germline mutations in SMARCA4 in all three families, we tested DNA from a fourth family, which also possessed a segregating SMARCA4 germline mutation. All familial tumors sequenced harboured either a somatic mutation or loss of the wild-type allele. Immunohistochemical (IHC) analysis of these and additional familial and non-familial cases showed loss of the SMARCA4 protein (BRG1) in 38/40 tumors overall. Sequencing of cases with available DNA revealed at least one germline or somatic deleterious SMARCA4 mutation in 30/32 cases. Additionally, the SCCOHT cell line BIN-67 contained bi-allelic deleterious mutations in SMARCA4. Our findings identify alterations in SMARCA4 as the major cause of SCCOHT, which could lead to genetic counseling and new treatment approaches.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-06T17:33:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000722","title":"UQCCR/QCMG brain metastasis sequence analysis","description":"The present study, conducted by the UQCCR and QCMG at the University of Queensland,  investigated the genomic landscape of brain metastases from 36 patients (with matched normal samples) that originated from a range of primary tumour sites (including breast (11), lung (18), melanoma (6) and oesophageal (1)) utilizing Illumina 2500 HiSeq Exome sequencing.  Somatic substitutions were identified using a dual qSNP/GATK calling strategy.  The Pindel tool was used to determined short insertions and deletions.  Key biological pathways were investigated using pathway analysis tools. It is envisaged that the current work may provide important biological insights into the genomic characterization and evolution of brain metastasis and additionally identify druggable targets of clinical relevance.","abstract":"The present study, conducted by the UQCCR and QCMG at the University of Queensland,  investigated the genomic landscape of brain metastases from 36 patients (with matched normal samples) that originated from a range of primary tumour sites (including breast (11), lung (18), melanoma (6) and oesophageal (1)) utilizing Illumina 2500 HiSeq Exome sequencing.  Somatic substitutions were identified using a dual qSNP/GATK calling strategy.  The Pindel tool was used to determined short insertions and deletions.  Key biological pathways were investigated using pathway analysis tools. It is envisaged that the current work may provide important biological insights into the genomic characterization and evolution of brain metastasis and additionally identify druggable targets of clinical relevance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-07T04:14:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000723","title":"ICGC Oesophageal adenocarcinoma - normal samples","description":"The oesophageal project will focus on adenocarcinoma which is increasing in incidence in the UK and other developed countries and has a very poor outcome. The primary aims of this project are to deeply sequence tumour and normal genomic DNA (including the precursor condition Barrett’s oesophagus when material is available) to provide a comprehensive catalogue of somatic mutations. This will be achieved through a UK-wide network of hospitals involved in a research collaboration called the OCCAMS consortium. The goal of this project is to use high quality clinical material with accurately annotated clinic-pathological, treatment and outcome data. - This study contains the Normal tissue samples.","abstract":"The oesophageal project will focus on adenocarcinoma which is increasing in incidence in the UK and other developed countries and has a very poor outcome. The primary aims of this project are to deeply sequence tumour and normal genomic DNA (including the precursor condition Barrett’s oesophagus when material is available) to provide a comprehensive catalogue of somatic mutations. This will be achieved through a UK-wide network of hospitals involved in a research collaboration called the OCCAMS consortium. The goal of this project is to use high quality clinical material with accurately annotated clinic-pathological, treatment and outcome data. - This study contains the Normal tissue samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-07T14:19:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000724","title":"ICGC Oesophageal adenocarcinoma - 100 tumour samples","description":"The oesophageal project will focus on adenocarcinoma which is increasing in incidence in the UK and other developed countries and has a very poor outcome. The primary aims of this project are to deeply sequence tumour and normal genomic DNA (including the precursor condition Barrett’s oesophagus when material is available) to provide a comprehensive catalogue of somatic mutations. This will be achieved through a UK-wide network of hospitals involved in a research collaboration called the OCCAMS consortium. The goal of this project is to use high quality clinical material with accurately annotated clinic-pathological, treatment and outcome data.","abstract":"The oesophageal project will focus on adenocarcinoma which is increasing in incidence in the UK and other developed countries and has a very poor outcome. The primary aims of this project are to deeply sequence tumour and normal genomic DNA (including the precursor condition Barrett’s oesophagus when material is available) to provide a comprehensive catalogue of somatic mutations. This will be achieved through a UK-wide network of hospitals involved in a research collaboration called the OCCAMS consortium. The goal of this project is to use high quality clinical material with accurately annotated clinic-pathological, treatment and outcome data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-07T15:10:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000725","title":"ICGC Oesophageal adenocarcinoma - tumour samples","description":"The oesophageal project will focus on adenocarcinoma which is increasing in incidence in the UK and other developed countries and has a very poor outcome. The primary aims of this project are to deeply sequence tumour and normal genomic DNA (including the precursor condition Barrett’s oesophagus when material is available) to provide a comprehensive catalogue of somatic mutations. This will be achieved through a UK-wide network of hospitals involved in a research collaboration called the OCCAMS consortium. The goal of this project is to use high quality clinical material with accurately annotated clinic-pathological, treatment and outcome data.","abstract":"The oesophageal project will focus on adenocarcinoma which is increasing in incidence in the UK and other developed countries and has a very poor outcome. The primary aims of this project are to deeply sequence tumour and normal genomic DNA (including the precursor condition Barrett’s oesophagus when material is available) to provide a comprehensive catalogue of somatic mutations. This will be achieved through a UK-wide network of hospitals involved in a research collaboration called the OCCAMS consortium. The goal of this project is to use high quality clinical material with accurately annotated clinic-pathological, treatment and outcome data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-07T15:12:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000726","title":"ICGC Oesophageal adenocarcinoma - Barrett's samples","description":"The oesophageal project will focus on adenocarcinoma which is increasing in incidence in the UK and other developed countries and has a very poor outcome. The primary aims of this project are to deeply sequence tumour and normal genomic DNA (including the precursor condition Barrett’s oesophagus when material is available) to provide a comprehensive catalogue of somatic mutations. This will be achieved through a UK-wide network of hospitals involved in a research collaboration called the OCCAMS consortium. The goal of this project is to use high quality clinical material with accurately annotated clinic-pathological, treatment and outcome data.","abstract":"The oesophageal project will focus on adenocarcinoma which is increasing in incidence in the UK and other developed countries and has a very poor outcome. The primary aims of this project are to deeply sequence tumour and normal genomic DNA (including the precursor condition Barrett’s oesophagus when material is available) to provide a comprehensive catalogue of somatic mutations. This will be achieved through a UK-wide network of hospitals involved in a research collaboration called the OCCAMS consortium. The goal of this project is to use high quality clinical material with accurately annotated clinic-pathological, treatment and outcome data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-07T15:14:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000727","title":"ICGC Oesophageal adenocarcinoma - lymph-node samples","description":"The oesophageal project will focus on adenocarcinoma which is increasing in incidence in the UK and other developed countries and has a very poor outcome. The primary aims of this project are to deeply sequence tumour and normal genomic DNA (including the precursor condition Barrett’s oesophagus when material is available) to provide a comprehensive catalogue of somatic mutations. This will be achieved through a UK-wide network of hospitals involved in a research collaboration called the OCCAMS consortium. The goal of this project is to use high quality clinical material with accurately annotated clinic-pathological, treatment and outcome data.","abstract":"The oesophageal project will focus on adenocarcinoma which is increasing in incidence in the UK and other developed countries and has a very poor outcome. The primary aims of this project are to deeply sequence tumour and normal genomic DNA (including the precursor condition Barrett’s oesophagus when material is available) to provide a comprehensive catalogue of somatic mutations. This will be achieved through a UK-wide network of hospitals involved in a research collaboration called the OCCAMS consortium. The goal of this project is to use high quality clinical material with accurately annotated clinic-pathological, treatment and outcome data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-07T15:16:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000728","title":"SPECTA__NGS_Screening_Program_for_Efficient_Clinical_Trial_Access","description":"SPECTA comprises a network of participating European clinical sites and NGS screening platforms that can screen individual patients for multiple molecular targets and potentially allow the design of trials that will match the specific biology of the diseases affecting specific patients with cancer.","abstract":"SPECTA comprises a network of participating European clinical sites and NGS screening platforms that can screen individual patients for multiple molecular targets and potentially allow the design of trials that will match the specific biology of the diseases affecting specific patients with cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-07T15:24:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000729","title":"Whole Exome Sequencing of cohorts of Mutant Braf mouse model melanoma DNA and germline DNA.","description":"Whole Exome Sequencing of cohorts of Mutant Braf mouse model melanoma DNA and germline DNA. The cohorts are (1) Mutant Braf mouse model melanomas, (2) Mutant Braf mouse model melanomas from UVR exposed mice and (3) Mutant Braf mouse model melanomas from UVR exposed, sunscreen protected mice.","abstract":"Whole Exome Sequencing of cohorts of Mutant Braf mouse model melanoma DNA and germline DNA. The cohorts are (1) Mutant Braf mouse model melanomas, (2) Mutant Braf mouse model melanomas from UVR exposed mice and (3) Mutant Braf mouse model melanomas from UVR exposed, sunscreen protected mice.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-10T12:29:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000730","title":"Metastatic_Prostate_Follow_Up","description":"Validation/deeper sequencing for metastatic prostate cancer samples","abstract":"Validation/deeper sequencing for metastatic prostate cancer samples","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-14T13:41:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000731","title":"Plasma RNA sequencing","description":"Plasma RNA sequencing","abstract":"Plasma RNA sequencing","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-14T13:47:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000732","title":"TMD_AMKL_targeted_follow_up_part_2","description":"Genomic libraries will be generated from total genomic DNA derived from 200+ patients with childhood Transient Myeloproliferative Disorder (TMD) and or Acute Megakaryocytic Leukemia (AMKL) as well some matched constitutional samples (n &lt; 50). Libraries will be enriched for a selected panel of genes using a bespoke pulldown protocol. 96 Samples will be individually barcoded and subjected to up to two lanes of Illumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the characterisation of known gene mutations in cancer as well as the validation of potentially novel variants identified by prior exome sequencing.","abstract":"Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. We have previously used exome sequencing in 10 paired samples from patients with TMD that have progressed to AMKL. As part of this study we plan to validate these mutations in an extended cohort of 200-400 patients with TMD – AMKL to identify novel gene mutations as well as characterise: the prevalence of these mutations, contribution n in disease progression from TMD to AMKL as well as study patterns of gene –gene interactions and genotype – phenotype associations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-14T13:55:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000733","title":"Barcelona_kids_with_melanoma","description":"This set of samples is composed of eight young people (7-16 years old) that have developed melanoma with first-degree relatives that have also developed cancer, which suggests a genetic component to their disease. Here we want to sequence these samples in order to find the causative mutations. As these samples do not carry any of the high-penetrance mutations known to date, finding the genes(s) responsible will offer new insights into the genetic mechanisms underlying predisposition to melanoma.","abstract":"This set of samples is composed of eight young people (7-16 years old) that have developed melanoma with first-degree relatives that have also developed cancer, which suggests a genetic component to their disease. Here we want to sequence these samples in order to find the causative mutations. As these samples do not carry any of the high-penetrance mutations known to date, finding the genes(s) responsible will offer new insights into the genetic mechanisms underlying predisposition to melanoma.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-17T13:10:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000734","title":"Genome wide association study on coronary heart disease in patients with familial hypercholesterolemia","description":"Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH.  We selected cases and controls with an extreme contrast in CHD risk from 17 000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established. The genome-wide association (GWA) study was performed on 249 very young FH cases with CHD and 217 old FH controls without CHD (above 65 years for males and 70 years of age for females) using the Illumina HumanHap 550K chip. In the next stage, two independent samples (one from the Netherlands and one from Italy, Norway, Spain, and the United Kingdom) of FH patients were used as replication samples. In the initial GWA analysis we identified 29 independent single nucleotide polymorphisms (SNPs) with suggestive associations with premature CHD (p&lt;1×10-4). We examined the association of these SNPs with CHD risk in the replication samples. After Bonferroni correction, none of the SNPs either replicated or reached genome-wide significance after combining the discovery and replication samples.  Therefore, we conclude that the genetics of CHD risk in FH is complex and even applying an ‘extreme genetics’ approach we did not identify new genetic risk variants. Most likely, this method is not as effective in leveraging effect size as anticipated, and may therefore not lead to significant gains in statistical power.  (NB submitten and conditionally accepted at European Journal of Human Genetics-please use abstract only for internal review until submission complete)","abstract":"Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH.  We selected cases and controls with an extreme contrast in CHD risk from 17 000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established. The genome-wide association (GWA) study was performed on 249 very young FH cases with CHD and 217 old FH controls without CHD (above 65 years for males and 70 years of age for females) using the Illumina HumanHap 550K chip. In the next stage, two independent samples (one from the Netherlands and one from Italy, Norway, Spain, and the United Kingdom) of FH patients were used as replication samples. In the initial GWA analysis we identified 29 independent single nucleotide polymorphisms (SNPs) with suggestive associations with premature CHD (p&lt;1×10-4). We examined the association of these SNPs with CHD risk in the replication samples. After Bonferroni correction, none of the SNPs either replicated or reached genome-wide significance after combining the discovery and replication samples.  Therefore, we conclude that the genetics of CHD risk in FH is complex and even applying an ‘extreme genetics’ approach we did not identify new genetic risk variants. Most likely, this method is not as effective in leveraging effect size as anticipated, and may therefore not lead to significant gains in statistical power.  (NB submitten and conditionally accepted at European Journal of Human Genetics-please use abstract only for internal review until submission complete)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-18T08:05:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000735","title":"Array CGH of cohorts of Mutant Braf mouse model melanoma DNA and germline DNA. The cohorts are (1) Mutant Braf mouse model melanomas and (2) Mutant Braf mouse model melanomas from UVR exposed mice.","description":"Array CGH of cohorts of Mutant Braf mouse model melanoma DNA and germline DNA. The cohorts are (1) Mutant Braf mouse model melanomas (n=15) and (2) Mutant Braf mouse model melanomas from UVR exposed mice (n=15).","abstract":"Array CGH of cohorts of Mutant Braf mouse model melanoma DNA and germline DNA. The cohorts are (1) Mutant Braf mouse model melanomas (n=15) and (2) Mutant Braf mouse model melanomas from UVR exposed mice (n=15).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000736","title":"Exome-seq, RNA-Seq, SNP array profiling of gastric tumor samples and cell lines.","description":"Gastric cancer is the second leading cause of worldwide cancer mortality, yet the underlying genomic alterations remain poorly understood. Here we performed exome and transcriptome sequencing and SNP array assays to characterize 51 primary gastric tumors and 32 cell lines. Meta-analysis of the exome data and previously published data sets revealed 24 significantly mutated genes in MSS tumors, and 16 in MSI tumors. More than half of the patients in our collection could potentially benefit from targeted therapies. We identified 55 splice-site mutations accompanied by aberrant splicing products, in addition to mutation-independent differential isoform usage in tumors. The ZAK kinase isoform TV1 is preferentially upregulated in gastric tumors and cell lines relative to normal samples. This pattern is also observed in colorectal, bladder, and breast cancers. Overexpression of this particular isoform activated multiple cancer-related transcription factor reporters, while depletion of ZAK in gastric cell lines inhibited proliferation. These results reveal the spectrum of genomic and transcriptomic alterations in gastric cancer, and identify isoform-specific oncogenic properties of ZAK.","abstract":"Gastric cancer is the second leading cause of worldwide cancer mortality, yet the underlying genomic alterations remain poorly understood. Here we performed exome and transcriptome sequencing and SNP array assays to characterize 51 primary gastric tumors and 32 cell lines. Meta-analysis of the exome data and previously published data sets revealed 24 significantly mutated genes in MSS tumors, and 16 in MSI tumors. More than half of the patients in our collection could potentially benefit from targeted therapies. We identified 55 splice-site mutations accompanied by aberrant splicing products, in addition to mutation-independent differential isoform usage in tumors. The ZAK kinase isoform TV1 is preferentially upregulated in gastric tumors and cell lines relative to normal samples. This pattern is also observed in colorectal, bladder, and breast cancers. Overexpression of this particular isoform activated multiple cancer-related transcription factor reporters, while depletion of ZAK in gastric cell lines inhibited proliferation. These results reveal the spectrum of genomic and transcriptomic alterations in gastric cancer, and identify isoform-specific oncogenic properties of ZAK.","study_type":"Other","pubmed_ids":[24807215],"external_links":null,"is_released":true,"released_date":"2014-03-18T19:06:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000737","title":"Next-Generation Sequencing of RNA and DNA Isolated from Paired Fresh-Frozen and Formalin-Fixed Paraffin-Embedded Samples of Human Cancer and Normal Tissue","description":"Formalin-fixed, paraffin-embedded (FFPE) tissues are an invaluable resource for clinical research. However, nucleic acids extracted from FFPE tissues are fragmented and chemically modified making them challenging to use in molecular studies. We analysed 23 fresh-frozen (FF), 35 FFPE and 38 paired FF/FFPE specimens, representing six different human tissue types (bladder, prostate and colon carcinoma; liver and colon normal tissue; reactive tonsil) in order to examine the potential use of FFPE samples in next-generation sequencing (NGS) based retrospective and prospective clinical studies. Two methods for DNA and three methods for RNA extraction from FFPE tissues were compared and were found to affect nucleic acid quantity and quality. DNA and RNA from selected FFPE and paired FF/FFPE specimens were used for exome and transcriptome analysis. Preparations of DNA Exome-Seq libraries was more challenging (29.5 % success) than that of RNA-Seq libraries, presumably because of modifications to FFPE tissue-derived DNA. Libraries could still be prepared from RNA isolated from two-decade old FFPE tissues. Data were analysed using the CLC Bio Genomics Workbench and revealed systematic differences between FF and FFPE tissue-derived nucleic acid libraries. In spite of this, pairwise analysis of DNA Exome-Seq data showed concordance for 70-80 % of variants in FF and FFPE samples stored for fewer than three years. RNA-Seq data showed high correlation of expression profiles in FF/FFPE pairs (Pearson Correlations of 0.90 +/- 0.05), irrespective of storage time (up to 244 months) and tissue type. A common set of 1,494 genes was identified with expression profiles that were significantly different between paired FF and FFPE samples irrespective of tissue type. Our results are promising and suggest that NGS can be used to study FFPE specimens in both prospective and retrospective archive-based studies in which FF specimens are not available.","abstract":"Formalin-fixed, paraffin-embedded (FFPE) tissues are an invaluable resource for clinical research. However, nucleic acids extracted from FFPE tissues are fragmented and chemically modified making them challenging to use in molecular studies. We analysed 23 fresh-frozen (FF), 35 FFPE and 38 paired FF/FFPE specimens, representing six different human tissue types (bladder, prostate and colon carcinoma; liver and colon normal tissue; reactive tonsil) in order to examine the potential use of FFPE samples in next-generation sequencing (NGS) based retrospective and prospective clinical studies. Two methods for DNA and three methods for RNA extraction from FFPE tissues were compared and were found to affect nucleic acid quantity and quality. DNA and RNA from selected FFPE and paired FF/FFPE specimens were used for exome and transcriptome analysis. Preparations of DNA Exome-Seq libraries was more challenging (29.5 % success) than that of RNA-Seq libraries, presumably because of modifications to FFPE tissue-derived DNA. Libraries could still be prepared from RNA isolated from two-decade old FFPE tissues. Data were analysed using the CLC Bio Genomics Workbench and revealed systematic differences between FF and FFPE tissue-derived nucleic acid libraries. In spite of this, pairwise analysis of DNA Exome-Seq data showed concordance for 70-80 % of variants in FF and FFPE samples stored for fewer than three years. RNA-Seq data showed high correlation of expression profiles in FF/FFPE pairs (Pearson Correlations of 0.90 +/- 0.05), irrespective of storage time (up to 244 months) and tissue type. A common set of 1,494 genes was identified with expression profiles that were significantly different between paired FF and FFPE samples irrespective of tissue type. Our results are promising and suggest that NGS can be used to study FFPE specimens in both prospective and retrospective archive-based studies in which FF specimens are not available.","study_type":"Other","pubmed_ids":[24878701],"external_links":null,"is_released":true,"released_date":"2014-03-19T15:20:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000738","title":"Whole-genome sequencing of bladder cancers of various stages and grades to search for driver mutations, chromosome-scale somatic changes, mutation signatures and clonal structures.","description":"This discovery set of tumours cancers with whole-genome sequence data comprised 14 bladder cancers, paired with peripheral blood, that had been collected from unrelated individuals presenting to the Urology Department, Royal Hallamshire Hospital, Sheffield between June 2008 and September 2011. Four cancers were of low-grade papillary morphology (pTaG1-2), five were high grade invading the lamina propria (pT1G3, with two subsequently becoming muscle-invasive); and five were muscle-invasive (pT2-pT3). All tumours were sampled at transurethral resection or cystectomy and had not previously received any other therapy. The presence of a majority of cancer cells in the tumour specimens was confirmed by routine histological assessment. Genomic DNA was extracted from each tumour and paired blood sample using standard methods.","abstract":"This discovery set of tumours cancers with whole-genome sequence data comprised 14 bladder cancers, paired with peripheral blood, that had been collected from unrelated individuals presenting to the Urology Department, Royal Hallamshire Hospital, Sheffield between June 2008 and September 2011. Four cancers were of low-grade papillary morphology (pTaG1-2), five were high grade invading the lamina propria (pT1G3, with two subsequently becoming muscle-invasive); and five were muscle-invasive (pT2-pT3). All tumours were sampled at transurethral resection or cystectomy and had not previously received any other therapy. The presence of a majority of cancer cells in the tumour specimens was confirmed by routine histological assessment. Genomic DNA was extracted from each tumour and paired blood sample using standard methods.","study_type":"Other","pubmed_ids":[24777035],"external_links":null,"is_released":true,"released_date":"2014-03-20T11:33:18+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000739","title":"Assessment_of_genetic_stability_in_human_iPS_cells","description":"In order to apply induced pluripotent stem cells to the clinic, it is important to have a deep understanding of the mutations  accrued through the process of reprogramming.  Through sequencing, it is possible not only to look at the genetic stability of iPS cells but also specifically where in the genome the mutations are occuring. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"In order to progress human induced pluripotent stem cells (hiPSCs) towards the clinic, several outstanding questions must be addressed. It is possible to reprogram different somatic cell types into hiPSCs  but it is unclear whether some cell types carry through fewer mutations through reprogramming. Through in depth analysis of hiPSCs generated from somatic cells, it will be possible to assess the variation in genetic stability of hiPSCs","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000740","title":"DNA_repair_in_BLM_deficient_hiPSCs","description":"We are aiming to investigate repair of a double strand break (DSB) within the genome in the presence and absence of the BLOOM protein. Zinc Finger Nucleases introduce DSBs at specified loci within the genome. Using sequencing we will assess the size of the deletion following repair. Protocol1. Transfect normal and BLOOM deficient human iPS cells with ZFNs, using AMXA2. Harvest cells after 5 days3. Perform column extraction of DNA4. PCR-amplify the ZFN region 5. Sequence and analyse repair of the DSBThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The BLOOM gene codes for a DNA helicase which is involved in DNA replication and repair. We have generated iPS cells from patients with BLOOM Syndrome. We'd like to investigate how the genome is repaired following a double strand break, in the context of normal and BLM deficient human iPSCs. We will induce site-specific double strand breaks with Zinc Finger Nucleases (ZFNs) and through amplicon sequencing compare the extent and type of damage following repair","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-20T14:11:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000741","title":"Assessment_of_epigenetic_variation_in_human_iPS_cells_Medip","description":"n order to progress human induced pluripotent stem cells (hiPSCs) towards the clinic, several outstanding questions must be addressed. It is possible to reprogram different somatic cell types into hiPSCs  and from studies in the mouse, it appears that an epigenetic memory of the starting cell type is carried over to hiPSCs. However a comprehensive comparative study of the characteristics of these hiPSCs has been missing from the literature. Importantly studies which aimed to address these aspects of hiPSCs have used cells from different patients. In order to avoid this important confounding variable and to keep the genetic background constant, tissue samples were procured from the patients and reprogrammed to iPS cells. The methylation status of these iPS cells will be compared.Protocol:Primary cell cultures were generated and reprogrammed to iPS cells. DNA was extracted and immunoprecipitated using anti-methyl cytosine and anti-hydroxymethyl cytosine antibodies.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This study aims to understand the role of the somatic cell in epigenetic reprogramming.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-20T14:11:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000742","title":"Role_of_Epigenetic_Memory_in_Human_Induced_Pluripotent_Stem_Cells_Pilot","description":"Fibroblasts have been shown to re-program into induced pluripotent stem (hiPS) cells, through over-expression of pluripotency genes. These hiPS cells show similar characteristics to embryonic stem cells including cell surface markers, epigenetic changes and ability to differentiate into the three germ layers. However it is unclear as to the extent of changes in gene expression through the re-programming process.. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Skin biopsies were taken from consented adults and the tissues dissociated to generate fibroblast cultures. These were re-programmed by retro-viral expression of pluripotency genes OCT-4, SOX-2, KLF-4 and C-MYC. The hiPS cells generated were tested as per standard criteria, with immunostaining, qPCR and in vitro assays of pluripotency namely directed differentiation and teratoma assays. Samples of cells were taken and the RNA extracted using a standard RNA preparation kit. These RNA samples were then entered to be sequenced.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-20T14:11:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000743","title":"Myeloma_Follow_up_Pilot","description":"Targeted capture of exonic and intronic regions of interest for the study of genomic alterations in multiple myeloma.","abstract":"The purpose of this study is to test the myeloma capture baitset S0631172 in terms of efficiency. Since we will study &gt;600 samples, we want to use a baitset that can reliably cover the regions of interest (SNPs, indels, CN). We included probes to the IGH locus; the performance in this locus is unknown and can potentially affect coverage of the remaining regions. We will study 24 cells lines in one lane of HiSeq (estimated coverage about 150X). 14 MM cell lines, 2 CLL cell lines, and 8 leukaemia cell lines. We will study reliability in calling variants in MM genes and CN abnormalities (hyperdiploid cases, prognostic CN changes). For the IGH locus, we want to study recurrent translocations, cancer-specific V(D)J rearrangements, and somatic hypermutations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-20T17:18:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000744","title":"ICGC medulloblastoma whole genome sequencing data, ICGC release 16","description":"ICGC medulloblastoma whole genome sequencing data, ICGC release 16","abstract":"ICGC medulloblastoma whole genome sequencing data, ICGC release 16","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-21T11:26:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000745","title":"McGill HumanMethylation 450K study of Naive T-Cells (suppressed)","description":"HumanMethylation 450K (suppressed)","abstract":"HumanMethylation 450K (suppressed)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000746","title":"Korean Lung Squamous-UNKNOWN","description":"lUNG","abstract":"lUNG","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000747","title":"ESGI_Exome_sequencing_in_Circulating_Tumor_Cells_to_determine_therapy_related_markers_____","description":"The objectives of this project are the identification of markers related to cancer therapy resistance in the blood of breast cancer patients and to study the genetic changes in cancer cells during this development of resistance. Whole genome amplified DNA from Circulating Tumor Cells (CTCs), selected during the course of systemic treatment from blood of metastatic breast cancer patients, will be exome sequenced . The patients selected for this study did not respond to therapy.","abstract":"The objectives of this project are the identification of markers related to cancer therapy resistance in the blood of breast cancer patients and to study the genetic changes in cancer cells during this development of resistance. Whole genome amplified DNA from Circulating Tumor Cells (CTCs), selected during the course of systemic treatment from blood of metastatic breast cancer patients, will be exome sequenced . The patients selected for this study did not respond to therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-26T13:51:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000748","title":"GWA on coronary heart disease in patients with familial hypercholesterolemia (FH)","description":"Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH.  We selected cases and controls with an extreme contrast in CHD risk from 17 000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established. The genome-wide association (GWA) study was performed on 249 very young FH cases with CHD and 217 old FH controls without CHD (above 65 years for males and 70 years of age for females) using the Illumina HumanHap 550K chip. In the next stage, two independent samples (one from the Netherlands and one from Italy, Norway, Spain, and the United Kingdom) of FH patients were used as replication samples. In the initial GWA analysis we identified 29 independent single nucleotide polymorphisms (SNPs) with suggestive associations with premature CHD (p&lt;1×10-4). We examined the association of these SNPs with CHD risk in the replication samples. After Bonferroni correction, none of the SNPs either replicated or reached genome-wide significance after combining the discovery and replication samples.  Therefore, we conclude that the genetics of CHD risk in FH is complex and even applying an ‘extreme genetics’ approach we did not identify new genetic risk variants. Most likely, this method is not as effective in leveraging effect size as anticipated, and may therefore not lead to significant gains in statistical power.","abstract":"Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH.  We selected cases and controls with an extreme contrast in CHD risk from 17 000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established. The genome-wide association (GWA) study was performed on 249 very young FH cases with CHD and 217 old FH controls without CHD (above 65 years for males and 70 years of age for females) using the Illumina HumanHap 550K chip. In the next stage, two independent samples (one from the Netherlands and one from Italy, Norway, Spain, and the United Kingdom) of FH patients were used as replication samples. In the initial GWA analysis we identified 29 independent single nucleotide polymorphisms (SNPs) with suggestive associations with premature CHD (p&lt;1×10-4). We examined the association of these SNPs with CHD risk in the replication samples. After Bonferroni correction, none of the SNPs either replicated or reached genome-wide significance after combining the discovery and replication samples.  Therefore, we conclude that the genetics of CHD risk in FH is complex and even applying an ‘extreme genetics’ approach we did not identify new genetic risk variants. Most likely, this method is not as effective in leveraging effect size as anticipated, and may therefore not lead to significant gains in statistical power.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000749","title":"Study of pediatric hepatocellular carcinoma caused by bile salt export pump deficiency","description":"Hepatocellular carcinoma (HCC) is almost invariably associated with an underlying inflammatory state, whose direct contribution to the acquisition of critical genomic changes is unclear. We mapped the acquired genomic alterations in human and mouse HCCs induced by defects in hepatocyte biliary transporters, which expose hepatocytes to bile salts and cause the onset of chronic inflammation that develops into cancer. In both human and mouse cancer genomes we found few somatic point mutations with no impairment of cancer genes, but instead massive gene amplification and rearrangements. This genomic landscape differs greatly from that of virus- and alcohol-associated liver cancer. Copy number gains preferentially occurred at late stages of cancer development and frequently targeted the MAPK signaling pathway, and in particular direct regulators of JNK. The pharmacological inhibition of JNK retarded cancer progression in the mouse. Our study demonstrates that intrahepatic cholestasis leading to hepatocyte exposure to bile acids and inflammation promotes cancer through genomic modifications that can be clearly distinguished from those determined by other etiological factors.","abstract":"Hepatocellular carcinoma (HCC) is almost invariably associated with an underlying inflammatory state, whose direct contribution to the acquisition of critical genomic changes is unclear. We mapped the acquired genomic alterations in human and mouse HCCs induced by defects in hepatocyte biliary transporters, which expose hepatocytes to bile salts and cause the onset of chronic inflammation that develops into cancer. In both human and mouse cancer genomes we found few somatic point mutations with no impairment of cancer genes, but instead massive gene amplification and rearrangements. This genomic landscape differs greatly from that of virus- and alcohol-associated liver cancer. Copy number gains preferentially occurred at late stages of cancer development and frequently targeted the MAPK signaling pathway, and in particular direct regulators of JNK. The pharmacological inhibition of JNK retarded cancer progression in the mouse. Our study demonstrates that intrahepatic cholestasis leading to hepatocyte exposure to bile acids and inflammation promotes cancer through genomic modifications that can be clearly distinguished from those determined by other etiological factors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-27T19:43:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000750","title":"Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis.","description":"Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC.","abstract":"Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC.","study_type":"Other","pubmed_ids":[25351503],"external_links":null,"is_released":true,"released_date":"2014-03-28T04:10:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000751","title":"Transposome_Bisulfite_Sequencing","description":"DNA belonging to 16 tumour/normal samples were treated with bisulfite, then up to 5 different bisulfite PCRs were performed in each one of the samples. Amplicons form the same sample were pooled and submitted to sequencing on a MiSeq platform.","abstract":"Pooled amplicon sequencing of bisulfite treated DNA.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-28T09:26:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000752","title":"BLUEPRINT EpiVar RNA-seq for Naive naive CD4+ T-cells","description":"BLUEPRINT EpiVar RNA-seq for Naive naive CD4+ T-cells","abstract":"BLUEPRINT EpiVar RNA-seq for Naive naive CD4+ T-cells","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-28T10:57:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000753","title":"BLUEPRINT EpiVar ChIP-seq for naive CD4+ T-cells","description":"BLUEPRINT EpiVar ChIP-seq for naive CD4+ T-cells","abstract":"BLUEPRINT EpiVar ChIP-seq for naive CD4+ T-cells","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-28T13:51:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001000754","title":"McGill WGBS-seq for naive T cells","description":"McGill WGBS-seq for naive T cells","abstract":"McGill WGBS-seq for naive T cells","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000755","title":"McGill Methylome capture for naive T-cells","description":"McGill Methylome capture for naive T-cells","abstract":"McGill Methylome capture for naive T-cells","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000756","title":"Metastatic_Prostate_Follow_Up_2","description":"Validation/deeper sequencing for metastatic prostate cancer samples","abstract":"Validation/deeper sequencing for metastatic prostate cancer samples","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-03-31T11:08:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000757","title":"TCELL_ATAC_SEQ_PILOT","description":"This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This is a pilot study to test ATAC-seq protocols. CD4+ and CD8+ cells have been obtained from three different anatomical compartments. We aim to assay open-chromatin regions across these cells and perform comparative analyses.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000758","title":"TCELL_PILOT_ATAC_SEQ","description":"This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This is a pilot study to test ATAC-seq protocols. CD4+ and CD8+ cells have been obtained from three different anatomical compartments. We aim to assay open-chromatin regions across these cells and perform comparative analyses.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-04-02T10:32:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000759","title":"Summary meta-analysis imputation data from 5 GWAS of colorectal cancer.","description":"To identify common variants influencing colorectal cancer (CRC) risk, we performed a meta-analysis of five genome-wide association studies, comprising 5,626 cases and 7,817 controls of European descent.","abstract":"To identify common variants influencing colorectal cancer (CRC) risk, we performed a meta-analysis of five genome-wide association studies, comprising 5,626 cases and 7,817 controls of European descent.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000760","title":"Unraveling metastatic progression of breast cancer","description":"To reconstruct the trajectories of BC progression, we performed exome sequencing (Illumina HiSeq2000, Truseq DNA sample preparation kit v2 and Exome Enrichment Kit v2; alignement done with BWA, substitutions and indels called with GATK and DINDEL respectively) coupled to validation by Sequenom and deep re-sequencing (ongoing), as well as copy number (CN) analyses (Oncoscan, Affymetrix) on DNA from matched primary (n=1-6/pt), axillary lymph node (ALN, n=1-6 for 4 pts), local recurrence (for 1 pt) and distant metastatic (n=1-5/pt) FFPE samples obtained from an autopsy series of 10 BC pts.","abstract":"To reconstruct the trajectories of BC progression, we performed exome sequencing (Illumina HiSeq2000, Truseq DNA sample preparation kit v2 and Exome Enrichment Kit v2; alignement done with BWA, substitutions and indels called with GATK and DINDEL respectively) coupled to validation by Sequenom and deep re-sequencing (ongoing), as well as copy number (CN) analyses (Oncoscan, Affymetrix) on DNA from matched primary (n=1-6/pt), axillary lymph node (ALN, n=1-6 for 4 pts), local recurrence (for 1 pt) and distant metastatic (n=1-5/pt) FFPE samples obtained from an autopsy series of 10 BC pts.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-04-03T17:58:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000761","title":"RNAseq data to study PRPF6 regulated splice forms in colon cancer cell lines","description":"Alternative splicing plays critical roles in differentiation, development, and cancer (Pettigrew et al., 2008; Chen and Manley, 2009). The recent identification of specific spliceosome inhibitors has generated interest in the therapeutic potential of targeting this cellular process (van Alphen et al., 2009). Using an integrated genomic approach, we have identified PRPF6, an RNA binding component of the pre-mRNA spliceosome, as an essential driver of oncogenesis in colon cancer. Importantly, PRPF6 is both amplified and overexpressed in colon cancer, and only colon cancer cells with high PRPF6 levels are sensitive to its loss. Our data clearly point to an important role for PRPF6 in colon cancer growth and suggest that a better understanding of its role in alternative splicing in colon cancer is warranted. To determine the specific alternative splice forms that PRPF6 regulates in colon cancer, we plan three experiments: 1. The first involves knocking down expression of PRPF6 in two different cancer cell lines with 3 different siRNAs, and then completing RNA-seq to determine the gene expression changes that occur relative to a non-targeting control siRNA. Because of the role for PRPF6 in pre-mRNA splicing, we especially want to quantify the changes in splice-specific forms of all genes genome-wide to identify genes whose splicing is altered upon PRPF6 knockdown. 2. The second involves immunoprecipitating PRPF6 from two different cancer cell lines and isolating any RNA that is bound to PRPF6, since PRPF6 is an RNA-binding protein. We then want to carry out RNA-seq to identify which RNA molecules co-immunoprecipitated with PRPF6. This will help us determine possible functions for PRPF6 in regulating colon cancer growth. 3. The third involves overexpressing PRPF6 in cell lines and then carrying out RNA-seq to identify any changes in splice-specific gene expression. This will allow us to determine whether increased PRPF6 expression is sufficient to drive alternative splicing changes.","abstract":"Alternative splicing plays critical roles in differentiation, development, and cancer (Pettigrew et al., 2008; Chen and Manley, 2009). The recent identification of specific spliceosome inhibitors has generated interest in the therapeutic potential of targeting this cellular process (van Alphen et al., 2009). Using an integrated genomic approach, we have identified PRPF6, an RNA binding component of the pre-mRNA spliceosome, as an essential driver of oncogenesis in colon cancer. Importantly, PRPF6 is both amplified and overexpressed in colon cancer, and only colon cancer cells with high PRPF6 levels are sensitive to its loss. Our data clearly point to an important role for PRPF6 in colon cancer growth and suggest that a better understanding of its role in alternative splicing in colon cancer is warranted. To determine the specific alternative splice forms that PRPF6 regulates in colon cancer, we plan three experiments: 1. The first involves knocking down expression of PRPF6 in two different cancer cell lines with 3 different siRNAs, and then completing RNA-seq to determine the gene expression changes that occur relative to a non-targeting control siRNA. Because of the role for PRPF6 in pre-mRNA splicing, we especially want to quantify the changes in splice-specific forms of all genes genome-wide to identify genes whose splicing is altered upon PRPF6 knockdown. 2. The second involves immunoprecipitating PRPF6 from two different cancer cell lines and isolating any RNA that is bound to PRPF6, since PRPF6 is an RNA-binding protein. We then want to carry out RNA-seq to identify which RNA molecules co-immunoprecipitated with PRPF6. This will help us determine possible functions for PRPF6 in regulating colon cancer growth. 3. The third involves overexpressing PRPF6 in cell lines and then carrying out RNA-seq to identify any changes in splice-specific gene expression. This will allow us to determine whether increased PRPF6 expression is sufficient to drive alternative splicing changes.","study_type":"Other","pubmed_ids":[24788092],"external_links":null,"is_released":true,"released_date":"2014-04-03T21:44:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000762","title":"Genetics_and_Networks_of_Congenital_Heart_Defects","description":"Exome sequencing of families with Congenital Heart Defects of diverse sub-phenotypes. Comprises both parent-offspring trios for sporadic cases and multiplex families. Collaboration with David Brook, University of Nottingham. Funded by the British Heart Foundation.","abstract":"Exome sequencing of families with Congenital Heart Defects of diverse sub-phenotypes. Comprises both parent-offspring trios for sporadic cases and multiplex families. Collaboration with David Brook, University of Nottingham. Funded by the British Heart Foundation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-04-07T16:36:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000763","title":"Expressed_fusion_transcripts_in_rare_bone_tumours","description":"mRNA-Seq on total RNA from primary osteoblastomas and phosphaturic mesenchymal tumours, focussing on fusion transcript expression","abstract":"This is a follow-up study following on from the analysis of wholegenome bone cancer sequencing.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-04-08T14:50:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000764","title":"SINGLE_CELL_ANALYSIS_OF_IN_VITRO_ERYTHROPOIESIS","description":"We are developing a protocol to differentiate mouse and human induced pluripotent stem (IPS) and embryonic stem (ES) cells towards the haematopoietic pathway to generate erythrocytes in vitro. This system has many applications such as the study of the role of specific genes and human polymorphisms in infectious diseases such as malaria, as well as haematological diseases such as myelodysplastic syndrome. The nature of the in vitro differentiation process means that a heterogeneous population of cells is generated. In order to understand the types of cells produced with our protocol, we have performed a single cell analysis, which has the power to reveal the different populations of cells and their characteristics. For this, a cDNA library has been made that needs to be sequenced to obtain the gene expression profiles of the different cells. With this information we will be able to assess the quality of the differentiation protocol and improve it in order to produce better cells for the downstream applications.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Erythrocytic cells are produced in vitro from pluripotent cells and analysed by a single cell approach to dissect the various populations of cells generated and their characteristic.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-04-10T10:56:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000765","title":"MPN_TGS2_Follow_up___PT1_Vori_other","description":"Targetted capture and resequencing of 94 known myeloid genes across MPN trials (PT1 and Voriconazole study) as well as remaining MPN samples. New bait design Jan 2014.","abstract":"Targetted capture and resequencing of 94 known myeloid genes across MPN trials (PT1 and Voriconazole study) as well as remaining MPN samples. New bait design Jan 2014.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-04-10T13:54:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000766","title":"MPN_Genomes_validation_and_interim_samples","description":"MPN genome variant validation and interrogation of interim timepoints.","abstract":"MPN genome variant validation and interrogation of interim timepoints.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-04-10T14:07:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000767","title":"Next generation sequencing of sporadic schwannomatosis samples","description":"Schwannomatosis (MIM #162091) is characterized by the development of multiple schwannomas without vestibular nerve involvement (which is a characteristic of neurofibromatosis type 2 - NF2). In an effort to detect novel genetic alterations predisposing to schwannomatosis, we sequenced eight tumor-blood DNA pairs from de novo schwannomatosis patients. The results of our study are present in the paper \"Whole exome sequencing reveals that the majority of schwannomatosis cases remain unexplained after excluding SMARCB1 and LZTR1 germline variants\" published in Acta Neuropathologica (PMID:25008767)","abstract":"Schwannomatosis (MIM #162091) is characterized by the development of multiple schwannomas without vestibular nerve involvement (which is a characteristic of neurofibromatosis type 2 - NF2). In an effort to detect novel genetic alterations predisposing to schwannomatosis, we sequenced eight tumor-blood DNA pairs from de novo schwannomatosis patients. The results of our study are present in the paper \"Whole exome sequencing reveals that the majority of schwannomatosis cases remain unexplained after excluding SMARCB1 and LZTR1 germline variants\" published in Acta Neuropathologica (PMID:25008767)","study_type":"Other","pubmed_ids":[25008767],"external_links":null,"is_released":true,"released_date":"2014-04-11T11:44:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000768","title":"Low_Coverage_Sequencing_of_rare_human_histiocytic_tumour","description":"Sequencing of rare human histiocytic tumour","abstract":"Sequencing of rare human histiocytic tumour","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-04-14T14:14:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000769","title":"Whole genome sequencing of 50 trios, where the child is affected with ID, and the parents are unaffected","description":"50 trios were whole genome sequenced with Complete Genomics to a depth of 80x. Each trio the child was affected with severe ID, and the parents were unaffected. All trios were negative for array, targetted gene and whole exome screening.","abstract":"50 trios were whole genome sequenced with Complete Genomics to a depth of 80x. Each trio the child was affected with severe ID, and the parents were unaffected. All trios were negative for array, targetted gene and whole exome screening.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-04-15T16:50:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000770","title":"APCDR Uganda GWAS: Genome wide sequence variation and susceptibility loci for cardiometabolic traits in a sub-Saharan African population (high depth family trio)","description":"Genomic studies in African populations provide unique opportunities to understand disease aetiology, human genetic diversity and population history in a regional and a global context. To leverage the relative benefits of different strategies, we undertook a combined approach of genotyping and whole-genome sequencing (WGS) in a population-based study of 6,400 individuals from a geographically defined rural community in South-West Uganda. We present data from 4,778 individuals with genotypes for ~2.2 million SNPs from the Uganda GWAS resource (UGWAS), and sequence data on up to 1,978 individuals spanning 41.5M SNPs and 4.5M indels (UG2G); 343 individuals overlap between the two datasets. Additionally, we sequenced at high coverage (30x) one Baganda family trio to serve as a high-confidence set to validate calling and filtering of variants in lower coverage data. We highlight the value of the largest sequence panel from Africa to date as a global resource for variant discovery, imputation and understanding the mutational spectrum and its clinical relevance in African populations. Alongside phenotype data, we provide a rich new genomic resource for researchers in Africa and globally.","abstract":"Genomic studies in African populations provide unique opportunities to understand disease aetiology, human genetic diversity and population history in a regional and a global context. To leverage the relative benefits of different strategies, we undertook a combined approach of genotyping and whole-genome sequencing (WGS) in a population-based study of 6,400 individuals from a geographically defined rural community in South-West Uganda. We present data from 4,778 individuals with genotypes for ~2.2 million SNPs from the Uganda GWAS resource (UGWAS), and sequence data on up to 1,978 individuals spanning 41.5M SNPs and 4.5M indels (UG2G); 343 individuals overlap between the two datasets. Additionally, we sequenced at high coverage (30x) one Baganda family trio to serve as a high-confidence set to validate calling and filtering of variants in lower coverage data. We highlight the value of the largest sequence panel from Africa to date as a global resource for variant discovery, imputation and understanding the mutational spectrum and its clinical relevance in African populations. Alongside phenotype data, we provide a rich new genomic resource for researchers in Africa and globally.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000771","title":"TO BE REUSED","description":"TO BE REUSED","abstract":"TO BE REUSED","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000772","title":"MYD88/TLR mutations in CLL","description":"The Chronic Lymphocytic Leukemia (CLL) Genome Project aims to identify genetic alterations involved in the development and progression of the CLL, which are still unknown, with the objective of generating a comprehensive catalogue of genetic alterations in 500 independent tumours. The CLL Genome Project, as a contributing member of the International Cancer Genome Consortium (ICGC), has the purposes of creating diagnostic tools, discovering therapeutic targets and developing new strategies that will allow a customized therapy for CLL in order to make it more precise and effective.","abstract":"The Chronic Lymphocytic Leukemia (CLL) Genome Project aims to identify genetic alterations involved in the development and progression of the CLL, which are still unknown, with the objective of generating a comprehensive catalogue of genetic alterations in 500 independent tumours. The CLL Genome Project, as a contributing member of the International Cancer Genome Consortium (ICGC), has the purposes of creating diagnostic tools, discovering therapeutic targets and developing new strategies that will allow a customized therapy for CLL in order to make it more precise and effective.","study_type":"Other","pubmed_ids":[24782504],"external_links":null,"is_released":true,"released_date":"2014-04-22T14:56:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000773","title":"WTCCC2 Visceral Leishmaniasis (VL) samples","description":"A WTCCC2 project genome-wide association study for visceral leishmaniasis (VL) in individuals from India, Brazil and Sudan, genotyped on the custom Illumina 670k array. The WTCCC2 analysis of the Brazilian and Indian samples is described in Fakiola et al. [Nat Genet. 2013 Feb;45(2):208-13].It should be noted that due to expected family structure in the data, normal analyses of these data should include an estimation of the relatedness between the samples. For more details about sample collection for the project please refer to the Methods section of the paper above. The samples from India were all collected from Bihar state in northeastern India. The Brazilian samples were collected from a wide area of northern Brazil, and managed at two laboratories in Natal and Belem. For more details on the geographic distribution of the Brazil samples please see Jamieson et al. [Genes Immun. 2007 Jan;8(1):84-90]. We have not generated qc_passed or info files for the Sudanese data, a preliminary scan of the data indicated that there may be DNA quality issues with these samples.","abstract":"A WTCCC2 project genome-wide association study for visceral leishmaniasis (VL) in individuals from India, Brazil and Sudan, genotyped on the custom Illumina 670k array. The WTCCC2 analysis of the Brazilian and Indian samples is described in Fakiola et al. [Nat Genet. 2013 Feb;45(2):208-13].It should be noted that due to expected family structure in the data, normal analyses of these data should include an estimation of the relatedness between the samples. For more details about sample collection for the project please refer to the Methods section of the paper above. The samples from India were all collected from Bihar state in northeastern India. The Brazilian samples were collected from a wide area of northern Brazil, and managed at two laboratories in Natal and Belem. For more details on the geographic distribution of the Brazil samples please see Jamieson et al. [Genes Immun. 2007 Jan;8(1):84-90]. We have not generated qc_passed or info files for the Sudanese data, a preliminary scan of the data indicated that there may be DNA quality issues with these samples.","study_type":"Other","pubmed_ids":[23291585],"external_links":null,"is_released":true,"released_date":"2014-04-24T12:44:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000774","title":"Heliconius_PacBio_scaffolding","description":"Improvement of the Heliconius melpomene melpomene reference genome using PacBio scaffolding.Genome size is ~300Mb. We aim for 10x coverage of the reference,and ~5x of various other related butterflies of interest.Overall 50 SMRT cells (~300Mb unique sequence each) and 10 libraries.For further inquiries regarding this data please contact;Dr Chris Jiggins,c.jiggins@zoo.cam.ac.uk,Tel: (+44)(0)1223 769021,University of Cambridge,Department of Zoology,This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Improvement of the Heliconius melpomene melpomene reference genome using PacBio scaffolding.Genome size is ~300Mb. We aim for 10x coverage of the reference,and ~5x of various other related butterflies of interest.Overall 50 SMRT cells (~300Mb unique sequence each) and 10 libraries.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000775","title":"Deciphering Developmental Disorders (DDD)","description":"The Deciphering Developmental Disorders (DDD) study is a research collaboration between the Wellcome Trust Sanger Institute, the NHS clinical genetics services and families across the UK and Ireland. The project aims to improve the diagnosis of children with developmental disorders by using high-resolution microarray and massively parallel sequencing technologies on 12,000 children and their parents. Genetic changes that explain the child's symptoms will be displayed in the DECIPHER database (https://decipher.sanger.ac.uk). Extended datasets generated by the DDD project will be available in the European Genome-Phenome Archive with access carefully managed by a Data Access Committee.","abstract":"The Deciphering Developmental Disorders (DDD) study is a research collaboration between the Wellcome Trust Sanger Institute, the NHS clinical genetics services and families across the UK and Ireland. The project aims to improve the diagnosis of children with developmental disorders by using high-resolution microarray and massively parallel sequencing technologies on 12,000 children and their parents. Genetic changes that explain the child's symptoms will be displayed in the DECIPHER database (https://decipher.sanger.ac.uk). Extended datasets generated by the DDD project will be available in the European Genome-Phenome Archive with access carefully managed by a Data Access Committee.","study_type":"Other","pubmed_ids":[25533962],"external_links":null,"is_released":true,"released_date":"2014-04-28T15:21:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000776","title":"Exome and mRNA were sequenced for 27 pairs of tumor/normal samples from lung adenocarcinoma in never smokers. DNA and RNA mutations were detected and compared along with gene expression pathway deregulation.","description":"Background. Novel and targetable mutations are needed for improved understanding and treatment of lung cancer in never-smokers. Methods. Twenty-seven lung adenocarcinomas from never-smokers were sequenced by both exome and mRNA-seq with respective normal tissues. Somatic mutations were detected and compared with pathway deregulation, tumor phenotypes and clinical outcomes. Results. Although somatic mutations in DNA or mRNA ranged from hundreds to thousands in each tumor, the overlap mutations between the two were only a few to a couple of hundreds. The number of somatic mutations from either DNA or mRNA was not significantly associated with clinical variables; however, the number of overlap mutations was associated with cancer subtype. The overlap mutations were preferentially expressed in mRNA. Ten genes (EGFR, TP53, KRAS, RPS6KB2, ATXN2, DHX9, PTPN13, SP1, SPTAN1 and MYOF) had recurrent mutations and these mutations were highly correlated with pathway deregulation and patient survival. Conclusions. The conserved recurrent mutations in RNAs are likely the driver for tumor biology, pathway deregulation and clinical outcomes. The information may be used for patient stratification and therapeutic target development.","abstract":"Background. Novel and targetable mutations are needed for improved understanding and treatment of lung cancer in never-smokers. Methods. Twenty-seven lung adenocarcinomas from never-smokers were sequenced by both exome and mRNA-seq with respective normal tissues. Somatic mutations were detected and compared with pathway deregulation, tumor phenotypes and clinical outcomes. Results. Although somatic mutations in DNA or mRNA ranged from hundreds to thousands in each tumor, the overlap mutations between the two were only a few to a couple of hundreds. The number of somatic mutations from either DNA or mRNA was not significantly associated with clinical variables; however, the number of overlap mutations was associated with cancer subtype. The overlap mutations were preferentially expressed in mRNA. Ten genes (EGFR, TP53, KRAS, RPS6KB2, ATXN2, DHX9, PTPN13, SP1, SPTAN1 and MYOF) had recurrent mutations and these mutations were highly correlated with pathway deregulation and patient survival. Conclusions. The conserved recurrent mutations in RNAs are likely the driver for tumor biology, pathway deregulation and clinical outcomes. The information may be used for patient stratification and therapeutic target development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000777","title":"Helq_Mouse_Knockouts__C__elegans_follow_up_","description":"FFPE Tumour samples from Helq mutant mouse models generated in the Boulton Lab","abstract":"FFPE Tumour samples from Helq mutant mouse models generated in the Boulton Lab","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000778","title":"Mutational_signatures_of_DNA_damage_and_repair_processes____Mutagen_Exposure_Pilot","description":"Pilot study for mutagen exposure work to be carried out as part of mutational signatures project.","abstract":"Pilot study for mutagen exposure work to be carried out as part of mutational signatures project. iPS cells exposed to different concentrations of mutagens will be analysed by Whole Exome Sequencing to determine mutations that have accumulated as a result of mutagen exposures.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000779","title":"Two lung cancer cell lines with EGFR mutations, PC-9 and KHM-3S, were either treated with Tarceva for 24 hours or left untreated. The gene expression profiles were examined by RNAseq, and the genome wide binding profiles of total STAT3 and pSTAT3 were characterized by ChIPseq.","description":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","abstract":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000780","title":"Two lung cancer cell lines with EGFR mutations, PC-9 and KHM-3S, were either treated with Tarceva for 24 hours or left untreated. The gene expression profiles were examined by RNAseq, and the genome wide binding profiles of total STAT3 and pSTAT3 were characterized by ChIPseq.","description":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","abstract":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000781","title":"Two lung cancer cell lines with EGFR mutations, PC-9 and KHM-3S, were either treated with Tarceva for 24 hours or left untreated. The gene expression profiles were examined by RNAseq, and the genome wide binding profiles of total STAT3 and pSTAT3 were characterized by ChIPseq.","description":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","abstract":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000782","title":"Two lung cancer cell lines with EGFR mutations, PC-9 and KHM-3S, were either treated with Tarceva for 24 hours or left untreated. The gene expression profiles were examined by RNAseq, and the genome wide binding profiles of total STAT3 and pSTAT3 were characterized by ChIPseq.","description":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","abstract":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000783","title":"Two lung cancer cell lines with EGFR mutations, PC-9 and KHM-3S, were either treated with Tarceva for 24 hours or left untreated. The gene expression profiles were examined by RNAseq, and the genome wide binding profiles of total STAT3 and pSTAT3 were characterized by ChIPseq.","description":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","abstract":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000784","title":"Two lung cancer cell lines with EGFR mutations, PC-9 and KHM-3S, were either treated with Tarceva for 24 hours or left untreated. The gene expression profiles were examined by RNAseq, and the genome wide binding profiles of total STAT3 and pSTAT3 were characterized by ChIPseq.","description":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","abstract":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000785","title":"Two lung cancer cell lines with EGFR mutations, PC-9 and KHM-3S, were either treated with Tarceva for 24 hours or left untreated. The gene expression profiles were examined by RNAseq, and the genome wide binding profiles of total STAT3 and pSTAT3 were characterized by ChIPseq.","description":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","abstract":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000786","title":"Two lung cancer cell lines with EGFR mutations, PC-9 and KHM-3S, were either treated with Tarceva for 24 hours or left untreated. The gene expression profiles were examined by RNAseq, and the genome wide binding profiles of total STAT3 and pSTAT3 were characterized by ChIPseq.","description":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","abstract":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000787","title":"Test Description","description":"Detail Test","abstract":"Detail Test","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000788","title":"TEst","description":"TEst","abstract":"TEst","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000789","title":"Moles","description":"In this project we have sequenced the exome of skin moles (melanocytic naevi) and also normal skin from young and old people. We are interested in looking at the clonality of these lesions and the burden of UV mutations","abstract":"In this project we have sequenced the exome of skin moles (melanocytic naevi) and also normal skin from young and old people. We are interested in looking at the clonality of these lesions and the burden of UV mutations","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-04-30T13:59:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000790","title":"Exploration_of__mutational_processes_in_human_cancer_cell_lines__Exome","description":"Approximately 25 cell lines representative of 11 mutation signatures have been selected and will be grown from a single cell, referred to as parental clone, for a period of 3 months to allow accumulation of mutations. Following that period, we will obtain 2 subclones from each of the parental clone for sequencing analysis. In total we will be sequencing 2 parental clones and 4 subclones per cell line for approximately 25 cell lines.","abstract":"One of the key questions to be explored is whether the biological processes generating specific mutational signatures continue to operate in the human cancer cell lines or simply reflect past mutagenic activity which is no longer operative. To address this question, we have extracted mutational signatures from 1,000 cancer cell lines of diverse cancer types. Several cell lines with mutational signatures of interest will be selected, subcloned over a defined period of time and their exomes sequenced. The increased load of the mutations representative of a specific mutational signature within the genome of a subclone when compared to its parental clone will be informative of the on-going mutational processes. To further confirm our observation from the exome-sequencing pilot project, whole genomes from parental clones and subclones of the cell lines with potentially on-going mutational processes will be sequenced.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-04-30T14:18:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000791","title":"test","description":"test","abstract":"test","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000792","title":"Two lung cancer cell lines with EGFR mutations, PC-9 and KHM-3S, were either treated with Tarceva for 24 hours or left untreated. The gene expression profiles were examined by RNAseq, and the genome wide binding profiles of total STAT3 and pSTAT3 were characterized by ChIPseq.","description":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","abstract":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000793","title":"Two lung cancer cell lines with EGFR mutations, PC-9 and KHM-3S, were either treated with Tarceva for 24 hours or left untreated. The gene expression profiles were examined by RNAseq, and the genome wide binding profiles of total STAT3 and pSTAT3 were characterized by ChIPseq.","description":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","abstract":"Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-04-30T15:34:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000794","title":"Reproducibility of variant calls in replicate next generation sequencing experiments","description":"In this study, we examined the reproducibility of nucleotide variant calls in replicate sequencing experiments of the same genomic DNA. We performed targeted sequencing of all known human protein kinase genes (kinome) (~3.3 Mb) using the SOLiD v4 platform. Seventeen breast cancer samples were sequenced in duplicate (n=14) or triplicate (n=3) to assess concordance of all calls and single nucleotide variant (SNV) calls.","abstract":"In this study, we examined the reproducibility of nucleotide variant calls in replicate sequencing experiments of the same genomic DNA. We performed targeted sequencing of all known human protein kinase genes (kinome) (~3.3 Mb) using the SOLiD v4 platform. Seventeen breast cancer samples were sequenced in duplicate (n=14) or triplicate (n=3) to assess concordance of all calls and single nucleotide variant (SNV) calls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000795","title":"Reproducibility of variant calls in replicate next generation sequencing experiments","description":"In this study, we examined the reproducibility of nucleotide variant calls in replicate sequencing experiments of the same genomic DNA. We performed targeted sequencing of all known human protein kinase genes (kinome) (~3.3 Mb) using the SOLiD v4 platform. Seventeen breast cancer samples were sequenced in duplicate (n=14) or triplicate (n=3) to assess concordance of all calls and single nucleotide variant (SNV) calls.","abstract":"In this study, we examined the reproducibility of nucleotide variant calls in replicate sequencing experiments of the same genomic DNA. We performed targeted sequencing of all known human protein kinase genes (kinome) (~3.3 Mb) using the SOLiD v4 platform. Seventeen breast cancer samples were sequenced in duplicate (n=14) or triplicate (n=3) to assess concordance of all calls and single nucleotide variant (SNV) calls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000796","title":"Reproducibility of variant calls in replicate next generation sequencing experiments","description":"In this study, we examined the reproducibility of nucleotide variant calls in replicate sequencing experiments of the same genomic DNA. We performed targeted sequencing of all known human protein kinase genes (kinome) (3.3 Mb) using the SOLiD v4 platform. Seventeen breast cancer samples were sequenced in duplicate (n=14) or triplicate (n=3) to assess concordance of all calls and single nucleotide variant (SNV) calls.","abstract":"In this study, we examined the reproducibility of nucleotide variant calls in replicate sequencing experiments of the same genomic DNA. We performed targeted sequencing of all known human protein kinase genes (kinome) (3.3 Mb) using the SOLiD v4 platform. Seventeen breast cancer samples were sequenced in duplicate (n=14) or triplicate (n=3) to assess concordance of all calls and single nucleotide variant (SNV) calls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000797","title":"Reproducibility of variant calls in replicate next generation sequencing experiments","description":"In this study, we examined the reproducibility of nucleotide variant calls in replicate sequencing experiments of the same genomic DNA. We performed targeted sequencing of all known human protein kinase genes (kinome) (3.3 Mb) using the SOLiD v4 platform. Seventeen breast cancer samples were sequenced in duplicate (n=14) or triplicate (n=3) to assess concordance of all calls and single nucleotide variant (SNV) calls.","abstract":"In this study, we examined the reproducibility of nucleotide variant calls in replicate sequencing experiments of the same genomic DNA. We performed targeted sequencing of all known human protein kinase genes (kinome) (3.3 Mb) using the SOLiD v4 platform. Seventeen breast cancer samples were sequenced in duplicate (n=14) or triplicate (n=3) to assess concordance of all calls and single nucleotide variant (SNV) calls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000798","title":"Reproducibility of variant calls in replicate next generation sequencing experiments","description":"In this study, we examined the reproducibility of nucleotide variant calls in replicate sequencing experiments of the same genomic DNA. We performed targeted sequencing of all known human protein kinase genes (kinome) (3.3 Mb) using the SOLiD v4 platform. Seventeen breast cancer samples were sequenced in duplicate (n=14) or triplicate (n=3) to assess concordance of all calls and single nucleotide variant (SNV) calls.","abstract":"In this study, we examined the reproducibility of nucleotide variant calls in replicate sequencing experiments of the same genomic DNA. We performed targeted sequencing of all known human protein kinase genes (kinome) (3.3 Mb) using the SOLiD v4 platform. Seventeen breast cancer samples were sequenced in duplicate (n=14) or triplicate (n=3) to assess concordance of all calls and single nucleotide variant (SNV) calls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000799","title":"TBA","description":"Analysis of mutational signatures caused by DNA repair defects in human induced pluripotent stem (iPS) cells. A reference human iPS cell line will be used for genetic manipulation to introduce homozygous knockouts of 100 genes known to be involved in or connected to DNA repair or DNA editing. Following a defined period of growth after homozygous knockout of each gene, sub clones will be generated and sequenced. The progenitor “parental” IPS cell line will be used to generate reference sequence data, in order to determine the mutational signature acquired due to the gene knockout.","abstract":"Analysis of mutational signatures caused by DNA repair defects in human induced pluripotent stem (iPS) cells. A reference human iPS cell line will be used for genetic manipulation to introduce homozygous knockouts of 100 genes known to be involved in or connected to DNA repair or DNA editing. Following a defined period of growth after homozygous knockout of each gene, sub clones will be generated and sequenced. The progenitor “parental” IPS cell line will be used to generate reference sequence data, in order to determine the mutational signature acquired due to the gene knockout.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000800","title":"Guardians_of_the_genome__protecting_DNA_from_endogenous_sources_of_damage_","description":"Analysis of mutational signatures caused by DNA repair defects in human induced pluripotent stem (iPS) cells. A reference human iPS cell line will be used for genetic manipulation to introduce homozygous knockouts of 100 genes known to be involved in or connected to DNA repair or DNA editing. Following a defined period of growth after homozygous knockout of each gene, sub clones will be generated and sequenced. The progenitor “parental” IPS cell line will be used to generate reference sequence data, in order to determine the mutational signature acquired due to the gene knockout.","abstract":"Mutational signatures are imprints of cell-intrinsic and extrinsic pathophysiological processes that have occurred through tumorigenesis. Experimental efforts to explore signature etiologies have produced a compendium of signatures of exogenous mutagens previously. Here, we unearth major sources of endogenous DNA damage and the genes that are critical to mitigating this innate stream of DNA damage under normal, physiological circumstances. We performed whole genome sequencing of 173 subclones of CRISPR-Cas9 knockouts of 43 genes in a human induced pluripotent stem cell system, in the absence of any added DNA damage. We reveal substitution and indel signatures that arise from those genes which are essential guardians of the genome. By detailed dissection and comparisons to cancer-derived signatures, we demonstrate interminable sources of constitutive DNA damage, and some mechanistic knowledge into how guardian genes preserve the genome. Based on these experimental insights, we develop and benchmark a tool for clinical classification of tumor samples.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-05-06T10:30:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000801","title":"TBA","description":"Analysis of mutational signatures arising in vivo in humans. iPS cells from control patients and100 patients carrying known mutations in DNA repair/editing genes will be generated, andsequenced.Blood from the patients will also be used to generate reference 'germline' sequence data.","abstract":"DNA in all cells is prone to mutagenesis, with somatic mutations making key contributions tovarious human diseases such as cancer, and to aging itself. Mutations may be theconsequence of exogenous or endogenous mutagenic influences (including radiations andDNA-damaging chemicals), and also result from the intrinsic infidelity of DNA replication orenzymatic DNA modifications. Somatic mutations are generally mitigated by the cellular DNArepair machinery, and defective functioning of components of this machinery can markedlyincrease mutation rates. Different mutational processes leave different, characteristicsignatures of somatic mutations on the exposed cellular genome. Notably, recent analyses ofcancer genomes have revealed several novel mutational signatures, the biological bases ofwhich are predominantly unknown. To generally elucidate somatic mutational processesoperative in cells, in particular their influences on human disease, we propose tosystematically survey the mutational signatures generated by exposures to known DNAdamaging agents and defective DNA repair/editing processes. These studies will provide aseries of mutational signatures with known underlying causes for subsequent matching tosignatures found in normal or diseased human cells, and will explore how various cellularcomponents influence mutagenesis. A “mutational signature” is the pattern of mutations occurring as a consequence of unfaithfulDNA replication, or as a result of an exposure to an endogenous or environmental mutagen.Mutational signatures include one or more classes of DNA change; base substitutions,insertions and deletions, rearrangements and copy number changes. They can be given extradiscriminatory power by further characterisation of each mutation class; for example, for basesubstitutions, by incorporating the subclass, the sequence context, the transcriptional strand,evidence of substitution clustering (kataegis) and other features relating to the genomic orepigenomic landscape.Mutational signatures extracted in this proposal will all be characterised by next generationsequencing of whole genomes of cell clones that have been exposed to a mutational processcaused by DNA damaging agents or abnormalities in DNA repair/editing.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-05-06T10:31:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000802","title":"TBA","description":"Analysis of mutational signatures arising in vivo in humans. iPS cells from control patients and100 patients carrying known mutations in DNA repair/editing genes will be generated, andsequenced.Blood from the patients will also be used to generate reference 'germline' sequence data.","abstract":"DNA in all cells is prone to mutagenesis, with somatic mutations making key contributions tovarious human diseases such as cancer, and to aging itself. Mutations may be theconsequence of exogenous or endogenous mutagenic influences (including radiations andDNA-damaging chemicals), and also result from the intrinsic infidelity of DNA replication orenzymatic DNA modifications. Somatic mutations are generally mitigated by the cellular DNArepair machinery, and defective functioning of components of this machinery can markedlyincrease mutation rates. Different mutational processes leave different, characteristicsignatures of somatic mutations on the exposed cellular genome. Notably, recent analyses ofcancer genomes have revealed several novel mutational signatures, the biological bases ofwhich are predominantly unknown. To generally elucidate somatic mutational processesoperative in cells, in particular their influences on human disease, we propose tosystematically survey the mutational signatures generated by exposures to known DNAdamaging agents and defective DNA repair/editing processes. These studies will provide aseries of mutational signatures with known underlying causes for subsequent matching tosignatures found in normal or diseased human cells, and will explore how various cellularcomponents influence mutagenesis. A “mutational signature” is the pattern of mutations occurring as a consequence of unfaithfulDNA replication, or as a result of an exposure to an endogenous or environmental mutagen.Mutational signatures include one or more classes of DNA change; base substitutions,insertions and deletions, rearrangements and copy number changes. They can be given extradiscriminatory power by further characterisation of each mutation class; for example, for basesubstitutions, by incorporating the subclass, the sequence context, the transcriptional strand,evidence of substitution clustering (kataegis) and other features relating to the genomic orepigenomic landscape.Mutational signatures extracted in this proposal will all be characterised by next generationsequencing of whole genomes of cell clones that have been exposed to a mutational processcaused by DNA damaging agents or abnormalities in DNA repair/editing.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-05-06T10:33:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000803","title":"TBA","description":"Analysis of mutational signatures arising in vivo in humans. iPS cells from control patients and100 patients carrying known mutations in DNA repair/editing genes will be generated, andsequenced.Blood from the patients will also be used to generate reference 'germline' sequence data.","abstract":"DNA in all cells is prone to mutagenesis, with somatic mutations making key contributions tovarious human diseases such as cancer, and to aging itself. Mutations may be theconsequence of exogenous or endogenous mutagenic influences (including radiations andDNA-damaging chemicals), and also result from the intrinsic infidelity of DNA replication orenzymatic DNA modifications. Somatic mutations are generally mitigated by the cellular DNArepair machinery, and defective functioning of components of this machinery can markedlyincrease mutation rates. Different mutational processes leave different, characteristicsignatures of somatic mutations on the exposed cellular genome. Notably, recent analyses ofcancer genomes have revealed several novel mutational signatures, the biological bases ofwhich are predominantly unknown. To generally elucidate somatic mutational processesoperative in cells, in particular their influences on human disease, we propose tosystematically survey the mutational signatures generated by exposures to known DNAdamaging agents and defective DNA repair/editing processes. These studies will provide aseries of mutational signatures with known underlying causes for subsequent matching tosignatures found in normal or diseased human cells, and will explore how various cellularcomponents influence mutagenesis. A “mutational signature” is the pattern of mutations occurring as a consequence of unfaithfulDNA replication, or as a result of an exposure to an endogenous or environmental mutagen.Mutational signatures include one or more classes of DNA change; base substitutions,insertions and deletions, rearrangements and copy number changes. They can be given extradiscriminatory power by further characterisation of each mutation class; for example, for basesubstitutions, by incorporating the subclass, the sequence context, the transcriptional strand,evidence of substitution clustering (kataegis) and other features relating to the genomic orepigenomic landscape.Mutational signatures extracted in this proposal will all be characterised by next generationsequencing of whole genomes of cell clones that have been exposed to a mutational processcaused by DNA damaging agents or abnormalities in DNA repair/editing.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-05-06T10:33:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000804","title":"TBA","description":"Analysis of mutational signatures arising in vivo in humans. iPS cells from control patients and100 patients carrying known mutations in DNA repair/editing genes will be generated, andsequenced.Blood from the patients will also be used to generate reference 'germline' sequence data.","abstract":"DNA in all cells is prone to mutagenesis, with somatic mutations making key contributions tovarious human diseases such as cancer, and to aging itself. Mutations may be theconsequence of exogenous or endogenous mutagenic influences (including radiations andDNA-damaging chemicals), and also result from the intrinsic infidelity of DNA replication orenzymatic DNA modifications. Somatic mutations are generally mitigated by the cellular DNArepair machinery, and defective functioning of components of this machinery can markedlyincrease mutation rates. Different mutational processes leave different, characteristicsignatures of somatic mutations on the exposed cellular genome. Notably, recent analyses ofcancer genomes have revealed several novel mutational signatures, the biological bases ofwhich are predominantly unknown. To generally elucidate somatic mutational processesoperative in cells, in particular their influences on human disease, we propose tosystematically survey the mutational signatures generated by exposures to known DNAdamaging agents and defective DNA repair/editing processes. These studies will provide aseries of mutational signatures with known underlying causes for subsequent matching tosignatures found in normal or diseased human cells, and will explore how various cellularcomponents influence mutagenesis. A “mutational signature” is the pattern of mutations occurring as a consequence of unfaithfulDNA replication, or as a result of an exposure to an endogenous or environmental mutagen.Mutational signatures include one or more classes of DNA change; base substitutions,insertions and deletions, rearrangements and copy number changes. They can be given extradiscriminatory power by further characterisation of each mutation class; for example, for basesubstitutions, by incorporating the subclass, the sequence context, the transcriptional strand,evidence of substitution clustering (kataegis) and other features relating to the genomic orepigenomic landscape.Mutational signatures extracted in this proposal will all be characterised by next generationsequencing of whole genomes of cell clones that have been exposed to a mutational processcaused by DNA damaging agents or abnormalities in DNA repair/editing.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000805","title":"RNA-seq data from the EUROBATS Project in four tissues: Fat, LCL, Skin and whole Blood.","description":"EUROBATS consists of RNA-seq data for  female twins in lisphoblastoide cell lines (LCL), abdominal adipose tissue (Fat), abdominal skin tissue (Skin) and whole blood (Blood). The samples are a combination of MZ twins, DZ twins and singletons. The goal of the project is to find biomarkers related with the ageing process and cellular senescence.","abstract":"EUROBATS consists of RNA-seq data for  female twins in lisphoblastoide cell lines (LCL), abdominal adipose tissue (Fat), abdominal skin tissue (Skin) and whole blood (Blood). The samples are a combination of MZ twins, DZ twins and singletons. The goal of the project is to find biomarkers related with the ageing process and cellular senescence.","study_type":"Other","pubmed_ids":[24771767,25436857],"external_links":null,"is_released":true,"released_date":"2014-05-06T11:22:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000806","title":"Reproducibility of variant calls in replicate next generation sequencing experiments","description":"In this study, we examined the reproducibility of nucleotide variant calls in replicate sequencing experiments of the same genomic DNA. We performed targeted sequencing of all known human protein kinase genes (kinome) (~3.3 Mb) using the SOLiD v4 platform. Seventeen breast cancer samples were sequenced in duplicate (n=14) or triplicate (n=3) to assess concordance of all calls and single nucleotide variant (SNV) calls.","abstract":"In this study, we examined the reproducibility of nucleotide variant calls in replicate sequencing experiments of the same genomic DNA. We performed targeted sequencing of all known human protein kinase genes (kinome) (~3.3 Mb) using the SOLiD v4 platform. Seventeen breast cancer samples were sequenced in duplicate (n=14) or triplicate (n=3) to assess concordance of all calls and single nucleotide variant (SNV) calls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000807","title":"Imputation-Based Meta-Analysis of Severe Malaria in Three African Populations","description":"To be done","abstract":"To be done","study_type":"Other","pubmed_ids":[23717212],"external_links":null,"is_released":true,"released_date":"2014-05-08T12:24:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000808","title":"Whole_exome_sequencing_CHD_trios","description":"Whole exome sequencing of families with Congenital Heart Defects (182 trios). Collaboration with David Brook, University of Nottingham.","abstract":"Whole exome sequencing of families with Congenital Heart Defects (182 trios). Collaboration with David Brook, University of Nottingham.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-05-08T13:55:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000809","title":"TRACERx: TRAcking non-small cell lung Cancer Evolution through therapy (Rx).  Pilot Study.  Multi-region sequencing of early-stage NSCLCs.","description":"Deciphering the complexity of non-small cell lung cancer (NSCLC) evolutionary histories may elucidate the basis for its dismal outcome. We performed multi-region sequencing of early-stage NSCLCs. Spatial dissection revealed branched tumor evolution, with driver mutations occurring before and after subclonal diversification. Intra-tumor heterogeneity in DNA copy number alterations, translocations and endogenous APOBEC mutational processes demonstrates that NSCLC may follow multiple distinct evolutionary trajectories simultaneously. In smokers, despite maintained carcinogen exposure, temporal dissection reveals a relative decrease in smoking-related mutations during tumor progression, accompanied by an increase in APOBEC-related mutations. In the tumors from ex-smokers, genome-doubling occurred before subclonal diversification, suggesting prolonged latency before clinical detection. Multi-region sequencing demonstrates the relentless and heterogeneous nature of genomic instability processes in early-stage NSCLCs.","abstract":"Deciphering the complexity of non-small cell lung cancer (NSCLC) evolutionary histories may elucidate the basis for its dismal outcome. We performed multi-region sequencing of early-stage NSCLCs. Spatial dissection revealed branched tumor evolution, with driver mutations occurring before and after subclonal diversification. Intra-tumor heterogeneity in DNA copy number alterations, translocations and endogenous APOBEC mutational processes demonstrates that NSCLC may follow multiple distinct evolutionary trajectories simultaneously. In smokers, despite maintained carcinogen exposure, temporal dissection reveals a relative decrease in smoking-related mutations during tumor progression, accompanied by an increase in APOBEC-related mutations. In the tumors from ex-smokers, genome-doubling occurred before subclonal diversification, suggesting prolonged latency before clinical detection. Multi-region sequencing demonstrates the relentless and heterogeneous nature of genomic instability processes in early-stage NSCLCs.","study_type":"Other","pubmed_ids":[25301630],"external_links":null,"is_released":true,"released_date":"2014-05-08T15:01:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000810","title":"Single_Cell_Mouse_DNA___Pilot_","description":"Pilot for single cell DNA sequencing of mouse single nuclei.","abstract":"Pilot study for mouse lineage project in collaboration with single cell core facility.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000811","title":"Single_Cell__Mouse_transcriptome___Pilot","description":"Pilot to differentiate cell types based on single cell transcriptome.","abstract":"Pilot study for mouse lineage project in collaboration with single cell core facility.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000812","title":"Discovery_of_resistance_mechanisms_to_the_BRAF_inhibitor_vemurafenib_in_metastatic_BRAF_mutant_melanoma","description":"We propose to biopsy 20 consented BRAF mutant melanoma patients at Addenbrooke's Hospital pre-treatment with vemurafenib and also upon the development of resistant disease, with the aim of using exome sequence and SNP6 data to identify novel sequence variants and copy number alterations that can be used to validate observed resistance mechanisms in our cell line models and also to use these models to inform as to likely candidate small molecule inhibitors to overcome resistance and that could be tested in the clinical trial setting.","abstract":"We propose to biopsy 20 consented BRAF mutant melanoma patients at Addenbrooke's Hospital pre-treatment with vemurafenib and also upon the development of resistant disease, with the aim of using exome sequence and SNP6 data to identify novel sequence variants and copy number alterations that can be used to validate observed resistance mechanisms in our cell line models and also to use these models to inform as to likely candidate small molecule inhibitors to overcome resistance and that could be tested in the clinical trial setting.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-05-09T14:35:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000813","title":"RNAseq___Discovery_of_resistance_mechanisms_to_the_BRAF_inhibitor_vemurafenib_in_metastatic_BRAF_mutant_melanoma","description":"We propose to biopsy 20 consented BRAF mutant melanoma patients at Addenbrooke's Hospital pre-treatment with vemurafenib and also upon the development of resistant disease, with the aim of using exome sequence and SNP6 data to identify novel sequence variants and copy number alterations that can be used to validate observed resistance mechanisms in our cell line models and also to use these models to inform as to likely candidate small molecule inhibitors to overcome resistance and that could be tested in the clinical trial setting.","abstract":"We propose to biopsy 20 consented BRAF mutant melanoma patients at Addenbrooke's Hospital pre-treatment with vemurafenib and also upon the development of resistant disease, with the aim of using exome sequence and SNP6 data to identify novel sequence variants and copy number alterations that can be used to validate observed resistance mechanisms in our cell line models and also to use these models to inform as to likely candidate small molecule inhibitors to overcome resistance and that could be tested in the clinical trial setting.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-05-09T14:40:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000814","title":"Study_to_investigate_the_prevalence__of_leukaemic_mutations_in_whole_blood_DNA_in_a_cohort_of_blood_donors","description":"The aim of this study is to ascertain whether leukaemic mutations exist within the blood of people with otherwise normal haematopoeisis. To satisfy this aim we plan to look for 7 known leukaemic mutations  in the whole blood DNA of a large cohort of blood donors who have normal haematopoesis.  Genomic regions around mutational sites have been amplified using a 2 step PCR process which involves barcoding of individual patients","abstract":"The aim of this study is to ascertain whether leukaemic mutations exist within the blood of people with otherwise normal haematopoeisis. To satisfy this aim we plan to look for 7 known leukaemic mutations  in the whole blood DNA of a large cohort of blood donors who have normal haematopoesis.  Genomic regions around mutational sites have been amplified using a 2 step PCR process which involves barcoding of individual patients","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-05-09T14:44:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000815","title":"Identification_of_drug_resistance_genes_in_melanoma_by_mRNA_gene_expression","description":"We aim to sequence the mRNA transcriptome of 22 human melanoma cell lines in biological triplicate in order to define the gene expression profile of each cell line. The data will be correlated to the mutation status and the sensitivity to a panel of drugs in order to identify genes whose deregulation is associated to drug resistanceThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We aim to sequence the mRNA transcriptome of 22 human melanoma cell lines in biological triplicate in order to define the gene expression profile of each cell line. The data will be correlated to the mutation status and the sensitivity to a panel of drugs in order to identify genes whose deregulation is associated to drug resistance","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-05-13T10:55:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000816","title":"Identification_of_drug_resistance_genes_in_melanoma_by_small_RNAs_expression_analysis","description":"We aim to sequence the small RNAs of 22 human melanoma cell lines in biological triplicate in order to define the microRNAs expression profile of each cell line. The data will be correlated to the mutation status and the sensitivity to a panel of drugs in order to identify genes whose deregulation is associated to drug resistanceThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We aim to sequence the small RNAs of 22 human melanoma cell lines in biological triplicate in order to define the microRNAs expression profile of each cell line. The data will be correlated to the mutation status and the sensitivity to a panel of drugs in order to identify genes whose deregulation is associated to drug resistance","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-05-13T11:12:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000817","title":"A WTCCC2 genome-wide association study for psychosis endophenotype (PE) in individuals from UK, Germany, Holland, Spain and Australia.","description":"A WTCCC2 project genome-wide association study for psychosis endophenotype (PE) in 5831 individuals from UK, Germany, Holland, Spain and Australia, genotyped on the Affymetrix 6.0 array. Information about the family structure of the samples can be found in the .info file which accompanies the data. It should be noted that a number of samples in this study have no phenotype information including sex, case status and family membership. Details of the WTCCC2 analysis can be found in Bramon et al. [Biol Psychiatry. 2014 Mar 1;75(5):386-97].","abstract":"A WTCCC2 project genome-wide association study for psychosis endophenotype (PE) in 5831 individuals from UK, Germany, Holland, Spain and Australia, genotyped on the Affymetrix 6.0 array. Information about the family structure of the samples can be found in the .info file which accompanies the data. It should be noted that a number of samples in this study have no phenotype information including sex, case status and family membership. Details of the WTCCC2 analysis can be found in Bramon et al. [Biol Psychiatry. 2014 Mar 1;75(5):386-97].","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-05-13T16:59:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000818","title":"Exploring Mutational Signatures of DNA Damage and Repair Processes","description":"Exploring Mutational Signatures of DNA Damage and Repair Processes","abstract":"Exploring Mutational Signatures of DNA Damage and Repair Processes","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000819","title":"Exploring Mutational Signatures of DNA Damage and Repair Processes","description":"DNA in all cells is prone to mutagenesis, with somatic mutations making key contributions to various human diseases such as cancer and to aging itself. Mutations may be the consequence of endogenous or exogenous mutagenic influences (such as radiation and DNA-damaging chemicals), and also result from the intrinsic infidelity of DNA replication or enzymatic DNA modifications. The damage associated with generating somatic mutations is generally mitigated by the cellular DNA repair machinery, and defective functioning of components of this machinery can markedly increase mutation rates. Different mutational processes leave different, characteristic signatures of somatic mutations on the exposed cellular genome. Mutational signatures include one or more classes of DNA change; base substitutions, insertions and deletions, rearrangements and copy number changes. Notably, recent analyses of cancer genomes have revealed several novel mutational signatures, the biological bases of which are predominantly unknown.To elucidate somatic mutational processes operative in cells, in particular their influences on human disease, we propose to systematically survey the mutational signatures generated by exposures to known DNA damaging agents and defective DNA repair/editing processes. These studies will provide a series of mutational signatures with known underlying causes for subsequent matching to signatures found in normal or diseased human cells, and will explore how various cellular components influence mutagenesis. Mutational signatures extracted in this study will be characterised by next generation sequencing of whole genomes of cell clones that have been exposed to a mutational process caused by DNA damaging agents or abnormalities in DNA repair/editing.","abstract":"DNA in all cells is prone to mutagenesis, with somatic mutations making key contributions to various human diseases such as cancer and to aging itself. Mutations may be the consequence of endogenous or exogenous mutagenic influences (such as radiation and DNA-damaging chemicals), and also result from the intrinsic infidelity of DNA replication or enzymatic DNA modifications. The damage associated with generating somatic mutations is generally mitigated by the cellular DNA repair machinery, and defective functioning of components of this machinery can markedly increase mutation rates. Different mutational processes leave different, characteristic signatures of somatic mutations on the exposed cellular genome. Mutational signatures include one or more classes of DNA change; base substitutions, insertions and deletions, rearrangements and copy number changes. Notably, recent analyses of cancer genomes have revealed several novel mutational signatures, the biological bases of which are predominantly unknown.To elucidate somatic mutational processes operative in cells, in particular their influences on human disease, we propose to systematically survey the mutational signatures generated by exposures to known DNA damaging agents and defective DNA repair/editing processes. These studies will provide a series of mutational signatures with known underlying causes for subsequent matching to signatures found in normal or diseased human cells, and will explore how various cellular components influence mutagenesis. Mutational signatures extracted in this study will be characterised by next generation sequencing of whole genomes of cell clones that have been exposed to a mutational process caused by DNA damaging agents or abnormalities in DNA repair/editing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000820","title":"Insignia","description":"Analysis of mutational signatures arising in vivo in humans. Patients who are born with naturally occurring defects in genes involved in DNA repair, or those with a history of exposure to DNA damaging agents provide a rare insight into the mutation patterns that can arise in human beings. Induced pluripotent stem (iPS) cells from such patients (in addition to “control” participants) will be generated, cultured for a defined period of growth and sequenced. Blood from the patients will also be used to generate 'germline' sequence data, in order to identify “normal” variations and permit identification of somatic mutations.","abstract":"Analysis of mutational signatures arising in vivo in humans. Patients who are born with naturally occurring defects in genes involved in DNA repair, or those with a history of exposure to DNA damaging agents provide a rare insight into the mutation patterns that can arise in human beings. Induced pluripotent stem (iPS) cells from such patients (in addition to “control” participants) will be generated, cultured for a defined period of growth and sequenced. Blood from the patients will also be used to generate 'germline' sequence data, in order to identify “normal” variations and permit identification of somatic mutations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000821","title":"Signatures – iPSC Gene Knockouts","description":"Analysis of mutational signatures caused by DNA repair defects in human induced pluripotent stem (iPS) cells. A reference human iPS cell-line will be used for genetic manipulation to introduce homozygous knockouts of 100 genes known to be involved in or connected to DNA repair or DNA editing. Following a defined period of growth after homozygous knockout of each gene, sub clones will be generated and sequenced. The progenitor “parental” IPS cell-line will be used to generate reference sequence data, in order to determine the mutational signature acquired due to the gene knockout.","abstract":"Analysis of mutational signatures caused by DNA repair defects in human induced pluripotent stem (iPS) cells. A reference human iPS cell-line will be used for genetic manipulation to introduce homozygous knockouts of 100 genes known to be involved in or connected to DNA repair or DNA editing. Following a defined period of growth after homozygous knockout of each gene, sub clones will be generated and sequenced. The progenitor “parental” IPS cell-line will be used to generate reference sequence data, in order to determine the mutational signature acquired due to the gene knockout.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000822","title":"Signatures – iPSC Mutagen Exposure","description":"Analysis of mutational signatures caused by exposure to known mutagens in human induced pluripotent stem (iPS) cells. A reference human iPS cell-line will be exposed to 100 chemicals known or proposed to be mutagenic. Following exposure to mutagen, cells will undergo a period of recovery before sub clones are generated and sequenced. The progenitor “parental” IPS cell-line will be used to generate reference sequence data, in order to determine the mutational signatures acquired as a result of exposure to different mutagens.","abstract":"Analysis of mutational signatures caused by exposure to known mutagens in human induced pluripotent stem (iPS) cells. A reference human iPS cell-line will be exposed to 100 chemicals known or proposed to be mutagenic. Following exposure to mutagen, cells will undergo a period of recovery before sub clones are generated and sequenced. The progenitor “parental” IPS cell-line will be used to generate reference sequence data, in order to determine the mutational signatures acquired as a result of exposure to different mutagens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000823","title":"Irish/UK atopic eczema case-control direct RNA sequencing from skin biopsies.","description":"Background: Atopic dermatitis (AD; eczema) is characterised by a widespread abnormality in cutaneous barrier function and propensity to inflammation. Filaggrin is a multifunctional protein and plays a key role in skin barrier formation. Loss-of-function mutations in the gene encoding filaggrin (FLG) are a highly significant risk factor for atopic disease but the molecular mechanisms leading to dermatitis remain unclear.  Objective: To interrogate tissue-specific variations in the expressed genome in the skin of children with AD, to investigate underlying pathomechanisms in atopic skin. Methods: We applied single molecule direct RNA sequencing to analyse the whole transcriptome using minimal tissue samples. Uninvolved skin biopsies from 26 paediatric AD cases were compared with site-matched samples from 10 non-atopic teenage controls. Cases and controls were screened for FLG genotype to stratify the dataset.  Results: 2430 differentially expressed genes (false discovery rate p&lt;0.05) were identified, of which 211 were significantly up-regulated and 490 down-regulated by &gt;2-fold. Gene ontology terms for ‘extracellular space’ and ‘defence response’ were enriched whilst ‘lipid metabolic processes’ were down-regulated. The subset of FLG wild-type cases showed dysregulation of genes involved with lipid metabolism, whilst filaggrin haploinsufficiency affected global gene expression and was characterized by a type 1 interferon-mediated stress response.  Conclusion: These analyses demonstrate the importance of extracellular space and lipid metabolism in atopic skin pathology, independent of FLG genotype, whilst an aberrant defence response is seen in FLG-mutant individuals. Genotype stratification of the large dataset has facilitated functional interpretation and may guide future therapy development.","abstract":"Background: Atopic dermatitis (AD; eczema) is characterised by a widespread abnormality in cutaneous barrier function and propensity to inflammation. Filaggrin is a multifunctional protein and plays a key role in skin barrier formation. Loss-of-function mutations in the gene encoding filaggrin (FLG) are a highly significant risk factor for atopic disease but the molecular mechanisms leading to dermatitis remain unclear.  Objective: To interrogate tissue-specific variations in the expressed genome in the skin of children with AD, to investigate underlying pathomechanisms in atopic skin. Methods: We applied single molecule direct RNA sequencing to analyse the whole transcriptome using minimal tissue samples. Uninvolved skin biopsies from 26 paediatric AD cases were compared with site-matched samples from 10 non-atopic teenage controls. Cases and controls were screened for FLG genotype to stratify the dataset.  Results: 2430 differentially expressed genes (false discovery rate p&lt;0.05) were identified, of which 211 were significantly up-regulated and 490 down-regulated by &gt;2-fold. Gene ontology terms for ‘extracellular space’ and ‘defence response’ were enriched whilst ‘lipid metabolic processes’ were down-regulated. The subset of FLG wild-type cases showed dysregulation of genes involved with lipid metabolism, whilst filaggrin haploinsufficiency affected global gene expression and was characterized by a type 1 interferon-mediated stress response.  Conclusion: These analyses demonstrate the importance of extracellular space and lipid metabolism in atopic skin pathology, independent of FLG genotype, whilst an aberrant defence response is seen in FLG-mutant individuals. Genotype stratification of the large dataset has facilitated functional interpretation and may guide future therapy development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000824","title":"Diverse modes of genomic alterations in hepatocellular carcinoma","description":"Hepatocellular carcinoma is the most prevalent type of liver cancer. We intended to study the genomic landscape of this disease. We conducted whole-genome, exome and transcriptome sequencing for 42 patients. We show diverse modes in which the HCC genome is affected in these patients, including well-known and novel mutations, structural variations, and Hepatitis B-virus integration into the genome.","abstract":"Hepatocellular carcinoma is the most prevalent type of liver cancer. We intended to study the genomic landscape of this disease. We conducted whole-genome, exome and transcriptome sequencing for 42 patients. We show diverse modes in which the HCC genome is affected in these patients, including well-known and novel mutations, structural variations, and Hepatitis B-virus integration into the genome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-05-15T23:22:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000825","title":"Whole_Exome_Sequencing_of_INTERVAL","description":"Whole exome sequencing of a subset of participants from the INTERVAL study.","abstract":"INTERVAL is a randomised controlled trial in up to 50,000 blood donors being conducted within the framework of the UK’s National Blood and Transplant service (NHSBT). The main objectives are to determine whether blood can be safely collected more frequently than present practice, and whether donation intervals can be tailored to the individual’s capacity to give blood. Added value is provided by this study’s creation of a national epidemiological bio-resource that will contribute to broader public health research. Here we propose to whole exome sequence a subset of participants from the INTERVAL cohort to be used as a control set of data. (http://www.intervalstudy.org.uk/)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-05-19T15:21:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000826","title":"Reproducibility of variant calls in replicate next generation sequencing experiments","description":"In this study, we examined the reproducibility of nucleotide variant calls in replicate sequencing experiments of the same genomic DNA. We performed targeted sequencing of all known human protein kinase genes (kinome) (~3.3 Mb) using the SOLiD v4 platform. Seventeen breast cancer samples were sequenced in duplicate (n=14) or triplicate (n=3) to assess concordance of all calls and single nucleotide variant (SNV) calls.","abstract":"In this study, we examined the reproducibility of nucleotide variant calls in replicate sequencing experiments of the same genomic DNA. We performed targeted sequencing of all known human protein kinase genes (kinome) (~3.3 Mb) using the SOLiD v4 platform. Seventeen breast cancer samples were sequenced in duplicate (n=14) or triplicate (n=3) to assess concordance of all calls and single nucleotide variant (SNV) calls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-05-19T16:44:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000827","title":"HCT_116_CombinationTherapy_Pooled_Project__ENU_Mutagenesis","description":"KRAS mutant CRC is currently in clinical trial with a combination of a MEK and Akt inhibitor. These patients will likely develop resistance to this combination. We aim to identify the mechanisms of resistance via ENU mutagenesis, with a view to identifying additional therapeutics which have the ability to overcome this resistance.","abstract":"ENU used to engender resistance to a combination of a MEK inhibitor and an Akt Inhibitor.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000828","title":"CGP_CORE_CELL_LINES___RNA_seq","description":"Graham to complete","abstract":"graham to complete","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-05-22T13:57:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000829","title":"Detection of Clinically Relevant Genetic Variants in Autism spectrum Disorder by Whole-Genome Sequencing","description":"Autism Spectrum Disorder (ASD) demonstrates high heritability and familial clustering, yet the genetic causes remain only partially understood as a result of extensive clinical and genomic heterogeneity. Whole-genome sequencing (WGS) shows promise as a tool for identifying ASD risk genes as well as unreported mutations in known loci, but an assessment of its full utility in an ASD group has not been performed. We used WGS to examine 32 families with ASD to detect de novo or rare inherited genetic variants predicted to be deleterious (loss-of-function and damaging missense mutations). Among ASD probands, we identified deleterious de novo mutations in six of 32 (19%) families and X-linked or autosomal inherited alterations in ten of 32 (31%) families (some had combinations of mutations). The proportion of families identified with such putative mutations was larger than has been previously reported; this yield was in part due to the comprehensive and uniform coverage afforded by WGS. Deleterious variants were found in four unrecognized, nine known, and eight candidate ASD risk genes. Examples include CAPRIN1 and AFF2 (both linked to FMR1, which is involved in fragile X syndrome), VIP (involved in social-cognitive deficits), and other genes such as SCN2A and KCNQ2 (linked to epilepsy), NRXN1, and CHD7, which causes ASD-associated CHARGE syndrome. Taken together, these results suggest that WGS and thorough bioinformatic analyses for de novo and rare inherited mutations will improve the detection of genetic variants likely to be associated with ASD or its accompanying clinical symptoms.","abstract":"Autism Spectrum Disorder (ASD) demonstrates high heritability and familial clustering, yet the genetic causes remain only partially understood as a result of extensive clinical and genomic heterogeneity. Whole-genome sequencing (WGS) shows promise as a tool for identifying ASD risk genes as well as unreported mutations in known loci, but an assessment of its full utility in an ASD group has not been performed. We used WGS to examine 32 families with ASD to detect de novo or rare inherited genetic variants predicted to be deleterious (loss-of-function and damaging missense mutations). Among ASD probands, we identified deleterious de novo mutations in six of 32 (19%) families and X-linked or autosomal inherited alterations in ten of 32 (31%) families (some had combinations of mutations). The proportion of families identified with such putative mutations was larger than has been previously reported; this yield was in part due to the comprehensive and uniform coverage afforded by WGS. Deleterious variants were found in four unrecognized, nine known, and eight candidate ASD risk genes. Examples include CAPRIN1 and AFF2 (both linked to FMR1, which is involved in fragile X syndrome), VIP (involved in social-cognitive deficits), and other genes such as SCN2A and KCNQ2 (linked to epilepsy), NRXN1, and CHD7, which causes ASD-associated CHARGE syndrome. Taken together, these results suggest that WGS and thorough bioinformatic analyses for de novo and rare inherited mutations will improve the detection of genetic variants likely to be associated with ASD or its accompanying clinical symptoms.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000830","title":"Mesothelioma_Whole_Genomes","description":"Genomic architecture of mesothelioma parent study is project 925.  This project is set up in parallel to project 925 in order to Whole genome sequence ten of the 59 tumours in that project.","abstract":"The genome-wide landscape of somatically acquired mutations in mesothelioma has not been deeply characterised to date, but advances in DNA sequencing technology now allow this to be addressed comprehensively. Harnessing massively parallel DNA sequencing platforms, we will identify somatically acquired point mutations in all coding regions of the genome from patients with mesothelioma. In addition, using paired-end sequencing, we will map copy number changes and genomic rearrangements from the same patients. Cancer is driven by the acquisition of mutations in genes co-ordinating key biological pathways. Discovering recurrently mutated genes in a given tumour type provides direct access to disease biology and potentially identifies novel therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-05-22T15:26:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000831","title":"GNT - Placeholder","description":"GNT - Placeholder","abstract":"GNT - Placeholder","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001000832","title":"Genomic Landscape of Fibrolamellar Hepatocellular Carcinoma","description":"Fibrolamellar hepatocellular carcinoma (FLC) is a rare type of primary liver cancer that often arises in children, adolescents and young adults. At the pathological level, FLC display pure morphology or can present with mixed morphology involving a conventional HCC component. Owing to the rarity of the disease, its genetic landscape is fully unknown. Pure FLC showed less chromosomic aberrations than mixed FLC and hepatocellular carcinoma arising in non-cirrhotic liverµ. Nevertheless; they displayed more gains in 16q23 and more LOH in 21q22. We also analyzed the mutational landscape of 8 FLC by whole-exome sequencing and showed mutations in the coagulation pathway.","abstract":"Fibrolamellar hepatocellular carcinoma (FLC) is a rare type of primary liver cancer that often arises in children, adolescents and young adults. At the pathological level, FLC display pure morphology or can present with mixed morphology involving a conventional HCC component. Owing to the rarity of the disease, its genetic landscape is fully unknown. Pure FLC showed less chromosomic aberrations than mixed FLC and hepatocellular carcinoma arising in non-cirrhotic liverµ. Nevertheless; they displayed more gains in 16q23 and more LOH in 21q22. We also analyzed the mutational landscape of 8 FLC by whole-exome sequencing and showed mutations in the coagulation pathway.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000833","title":"Transcriptional Profiling of Pure Fibrolamellar Hepatocellular Carcinoma Reveals an Endocrine Signature","description":"Fibrolamellar hepatocellular carcinoma (FLC) is a rare type of primary liver cancer that often arises in children, adolescents and young adults. At the pathological level, FLC display pure morphology or can present with mixed morphology involving a conventional HCC component. Owing to the rarity of the disease, its genetic landscape is fully unknown. Pure FLC showed less chromosomic aberrations than mixed FLC and hepatocellular carcinoma arising in non-cirrhotic liverµ. Nevertheless; they displayed more gains in 16q23 and more LOH in 21q22. We also analyzed the mutational landscape of 8 FLC by whole-exome sequencing and showed mutations in the coagulation pathway.","abstract":"Fibrolamellar hepatocellular carcinoma (FLC) is a rare type of primary liver cancer that often arises in children, adolescents and young adults. At the pathological level, FLC display pure morphology or can present with mixed morphology involving a conventional HCC component. Owing to the rarity of the disease, its genetic landscape is fully unknown. Pure FLC showed less chromosomic aberrations than mixed FLC and hepatocellular carcinoma arising in non-cirrhotic liverµ. Nevertheless; they displayed more gains in 16q23 and more LOH in 21q22. We also analyzed the mutational landscape of 8 FLC by whole-exome sequencing and showed mutations in the coagulation pathway.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000834","title":"Mouse_Genomes_Strains_WGS","description":"Whole-genome sequencing on PacBio of laboratory mouse strains. See http://www.sanger.ac.uk/resources/mouse/genomes/ for more details. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Whole-genome sequencing on PacBio of laboratory mouse strains. See http://www.sanger.ac.uk/resources/mouse/genomes/ for more details.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000835","title":"Mutation_rates_in_normal_mouse_tissue___pilot_1","description":"This pilot contains 9 samples from 1 wildtype mouse plus 1 sample for each parent for whole genome sequencing.","abstract":"This is a pilot for the mouse lineage project, in which we try to determine the lineage of (wildtype) mouse cells. This is the first in-depth genome analysis of the mice we will use for this project.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000836","title":"FFPE_Normal_Panel_V3_Cancer_Panel","description":"FFPE normal panel generation for use with V3 cancer panel 0618521","abstract":"FFPE normal panel generation for use with V3 cancer panel 0618521","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-05-30T13:21:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000837","title":"Lung_Progression_versus_Regression_Whole_Genome_Sequencing","description":"Around 50 samples of pre-invasive lung cancer lesions showing subsequent clinical and pathological progression or regression","abstract":"Around 50 samples of pre-invasive lung cancer lesions showing subsequent clinical and pathological progression or regression","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-05-30T13:22:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000838","title":"Embryonic_variants_in_mouse_pancreas_and_liver_organoids","description":"Sequencing PCRs on WGA amplified mouse organoid tissue.","abstract":"Determining lineage tree of single cell derived mouse organoids by sequencing 35 embryonic variants identified in project 940/Sam Behjati.Assess set of 80 highly variable microsatellite loci for this purpose.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000839","title":"Targeting the DNA Repair Pathway in Ewing Sarcoma","description":"Ewing’s Sarcoma is a bone and soft tissue tumor that primarily affects adolescents and young adults. With current therapies, 70% of patients with localized disease survive but survival for metastatic and recurrent disease is poor. Whole genome sequencing of 19 Ewing’s Sarcoma tumors showed that STAG2 was mutated in 10% (2/19) of the tumors and STAG2 protein was absent in 14% (13/106) tumors by immunohistochemical staining. Previous studies have shown that glioblastoma cells lacking STAG2 are more sensitive to poly-ADP ribose polymerase (PARP) inhibitors. We found that Ewing’s Sarcoma cell lines are sensitive to PARP inhibitors irrespective of STAG2 protein expression. Ewing Sarcoma cell lines are defective in double strand DNA break repair. PARP inhibitor cytotoxicity in Ewing’s Sarcoma cells was potentiated 10-1,000 fold by DNA damaging agents (irinotecan and temozolomide). To extend these studies in vivo, we developed an orthotopic Ewing’s Sarcoma mouse model and performed pharmacokinetic and pharmacodynamic studies with three different PARP inhibitors (BMN-673, olaparib and veliparib) in clinical development for pediatric cancer. Those data were used to design preclinical phase I studies to identify tolerable drug combinations for pilot efficacy testing (preclinical phase II). Based on the results of the preclinical phase I/II data, we performed a double blind, randomized, placebo controlled preclinical phase III trial with 274 mice in 15 treatment groups. Irinotecan administered in a low-dose protracted schedule optimized for pediatric patients was an effective DNA damaging agent to combine with olaparib and BMN-673 and was better tolerated than combinations with temozolomide. Combining olaparib or BMN-673 with irinotecan and temozolomide gave complete and durable responses in over 80% of the mice.","abstract":"Ewing’s Sarcoma is a bone and soft tissue tumor that primarily affects adolescents and young adults. With current therapies, 70% of patients with localized disease survive but survival for metastatic and recurrent disease is poor. Whole genome sequencing of 19 Ewing’s Sarcoma tumors showed that STAG2 was mutated in 10% (2/19) of the tumors and STAG2 protein was absent in 14% (13/106) tumors by immunohistochemical staining. Previous studies have shown that glioblastoma cells lacking STAG2 are more sensitive to poly-ADP ribose polymerase (PARP) inhibitors. We found that Ewing’s Sarcoma cell lines are sensitive to PARP inhibitors irrespective of STAG2 protein expression. Ewing Sarcoma cell lines are defective in double strand DNA break repair. PARP inhibitor cytotoxicity in Ewing’s Sarcoma cells was potentiated 10-1,000 fold by DNA damaging agents (irinotecan and temozolomide). To extend these studies in vivo, we developed an orthotopic Ewing’s Sarcoma mouse model and performed pharmacokinetic and pharmacodynamic studies with three different PARP inhibitors (BMN-673, olaparib and veliparib) in clinical development for pediatric cancer. Those data were used to design preclinical phase I studies to identify tolerable drug combinations for pilot efficacy testing (preclinical phase II). Based on the results of the preclinical phase I/II data, we performed a double blind, randomized, placebo controlled preclinical phase III trial with 274 mice in 15 treatment groups. Irinotecan administered in a low-dose protracted schedule optimized for pediatric patients was an effective DNA damaging agent to combine with olaparib and BMN-673 and was better tolerated than combinations with temozolomide. Combining olaparib or BMN-673 with irinotecan and temozolomide gave complete and durable responses in over 80% of the mice.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-02T15:36:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000840","title":"Spatial and temporal diversity in genomic instability processes define early stage lung cancer evolution.","description":"Deciphering the complexity of non-small cell lung cancer (NSCLC) evolutionary histories may elucidate the basis for its dismal outcome. We performed multi-region sequencing on 25 regions from seven early-stage NSCLCs. Spatial dissection revealed branched tumor evolution, with driver mutations occurring before and after subclonal diversification. Intra-tumor heterogeneity in DNA copy number alterations, translocations and endogenous APOBEC mutational processes, demonstrates that NSCLC may follow multiple distinct evolutionary trajectories simultaneously. In smokers, despite maintained carcinogen exposure, temporal dissection reveals a proportional decrease in smoking-related mutations during tumor progression, accompanied by an increase in APOBEC-related mutations. We observed genome-doubling events early in tumor development of ex-smokers, suggesting prolonged latency periods before clinical detection. Multi-region sequencing demonstrates the relentless and heterogeneous nature of genomic instability processes in early-stage NSCLCs.","abstract":"Deciphering the complexity of non-small cell lung cancer (NSCLC) evolutionary histories may elucidate the basis for its dismal outcome. We performed multi-region sequencing on 25 regions from seven early-stage NSCLCs. Spatial dissection revealed branched tumor evolution, with driver mutations occurring before and after subclonal diversification. Intra-tumor heterogeneity in DNA copy number alterations, translocations and endogenous APOBEC mutational processes, demonstrates that NSCLC may follow multiple distinct evolutionary trajectories simultaneously. In smokers, despite maintained carcinogen exposure, temporal dissection reveals a proportional decrease in smoking-related mutations during tumor progression, accompanied by an increase in APOBEC-related mutations. We observed genome-doubling events early in tumor development of ex-smokers, suggesting prolonged latency periods before clinical detection. Multi-region sequencing demonstrates the relentless and heterogeneous nature of genomic instability processes in early-stage NSCLCs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-03T11:46:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000841","title":"HumanMethylation450K data from Purified Plasma Cells of Monoclonal gammopathy of unknown significance and Multiple myeloma patients and Healthy donors","description":"HumanMethylation450K data from Purified Plasma Cells of Monoclonal gammopathy of unknown significance and Multiple myeloma patients and Healthy donors","abstract":"HumanMethylation450K data from Purified Plasma Cells of Monoclonal gammopathy of unknown significance and Multiple myeloma patients and Healthy donors","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-03T13:37:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000842","title":"Whole genome sequence-based analysis of the genetics of longevity and cognitive aging in two female octogenarians","description":"A better knowledge of the genetics of aging will prove helpful in understanding the underlying biological processes. Here, we describe the whole genome sequences of two female octogenarians with maintained cognitive functions. These genomes allow for (i) identification of genomic variants that the two octogenarians have in common, (ii) assessment of the genetic disease propensities of and the presence of previously described variants promoting longevity in the octogenarians and (iii) the identification of a number of healthy-cognitive-aging candidate genetic loci awaiting confirmation in larger studies.","abstract":"A better knowledge of the genetics of aging will prove helpful in understanding the underlying biological processes. Here, we describe the whole genome sequences of two female octogenarians with maintained cognitive functions. These genomes allow for (i) identification of genomic variants that the two octogenarians have in common, (ii) assessment of the genetic disease propensities of and the presence of previously described variants promoting longevity in the octogenarians and (iii) the identification of a number of healthy-cognitive-aging candidate genetic loci awaiting confirmation in larger studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000843","title":"Genomic analysis of Smoothened inhibitor resistance in basal cell carcinoma","description":"Genomic analysis of Smoothened inhibitor resistance in basal cell carcinoma","abstract":"Genomic analysis of Smoothened inhibitor resistance in basal cell carcinoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000844","title":"def","description":"ghi","abstract":"ghi","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000845","title":"Genomic analysis of Smoothened inhibitor resistance in basal cell carcinoma","description":"Smoothened inhibitors are currently being investigated for the treatment of several cancers. Vismodegib is approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). The majority of BCC patients treated with vismodegib experience significant clinical benefit, however, a small number of patients develop resistance. Knowledge of resistance mechanisms can generate predictive biomarkers and is critical for the design of additional therapeutic strategies aimed at circumventing resistance. To investigate mechanisms of resistance to vismodegib in BCC we sequenced and profiled biopsies from patients who initially responded to treatment and subsequently progressed on drug.We find that resistance is associated with re-activation of the Hedgehog (Hh) pathway through diverse mechanisms, including concurrent copy number alterations in the downstream Hh pathway components SUFU and GLI2, as well as novel SMO mutations that reduce sensitivity to vismodegib. The latter fall into two classes: those that activate SMO and those that directly affect the vismodegib-binding pocket. Additionally, we observe evidence of clonal selection of SMO mutations and intra-tumor heterogeneity of resistance mechanisms, which implies diverse and combinatorial strategies are required to overcome resistance.","abstract":"Smoothened inhibitors are currently being investigated for the treatment of several cancers. Vismodegib is approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). The majority of BCC patients treated with vismodegib experience significant clinical benefit, however, a small number of patients develop resistance. Knowledge of resistance mechanisms can generate predictive biomarkers and is critical for the design of additional therapeutic strategies aimed at circumventing resistance. To investigate mechanisms of resistance to vismodegib in BCC we sequenced and profiled biopsies from patients who initially responded to treatment and subsequently progressed on drug.We find that resistance is associated with re-activation of the Hedgehog (Hh) pathway through diverse mechanisms, including concurrent copy number alterations in the downstream Hh pathway components SUFU and GLI2, as well as novel SMO mutations that reduce sensitivity to vismodegib. The latter fall into two classes: those that activate SMO and those that directly affect the vismodegib-binding pocket. Additionally, we observe evidence of clonal selection of SMO mutations and intra-tumor heterogeneity of resistance mechanisms, which implies diverse and combinatorial strategies are required to overcome resistance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-03T23:33:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000846","title":"BLUEPRINT HumanMethylation 450K study of Type 1 diabetes mellitus patients (QMUL) (suppressed)","description":"BLUEPRINT HumanMethylation 450K study of Type 1 diabetes mellitus patients (QMUL) (suppressed)","abstract":"BLUEPRINT HumanMethylation 450K study of Type 1 diabetes mellitus patients (QMUL) (suppressed)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000847","title":"BLUEPRINT HumanMethylation 450K study of Monocyte, Neutrophil and T-Cell samples from Healthy donor (UCL) (suppressed)","description":"BLUEPRINT HumanMethylation 450K study of Monocyte, Neutrophil and T-Cell samples from Healthy donor (UCL) (suppressed)","abstract":"BLUEPRINT HumanMethylation 450K study of Monocyte, Neutrophil and T-Cell samples from Healthy donor (UCL) (suppressed)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000848","title":"Transcriptome_profiling_of_mutant_embryos_from_the_Mouse_Genetics_Project__DMDD_","description":"Total RNA was extracted from embryonic lethal homozygous gene knockout and sibling embryos from the Mouse Genetics Project (http://www.dmdd.org.uk/). Protocol: Total RNA was extracted and DNase treated. After fragmentation RNA was enriched for the 3’ ends by pull down using an anchored polyT oligo attached to magnetic beads. An RNA oligo comprising part of the Illumina adapter 2 was ligated to the 5’ end of the captured RNA and the RNA was eluted from the beads. Reverse transcription was primed with an anchored polyT oligo with part of Illumina adapter 1 at the 5’ end followed by 12 random bases, then an 8 base indexing tag, then CG and 14 T bases. An Illumina library with full adapter sequence was produced by 20 cycles of PCR. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Paired-end sequence data from Illumina HiSeq was prepared from mouse embryos from the Mouse Genetics Project for transcriptome profiling","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000849","title":"Celiac disease case-control North Indian Immunochip dataset","description":"Illumina Immunochip genotype data for coeliac disease and control samples of North Indian samples origin. Data is in PLINK binary format. Calling algorithm for genotypes is based on GenomeStudio (GenTrain), with manual clustering of selected variants.","abstract":"Illumina Immunochip genotype data for coeliac disease and control samples of North Indian samples origin. Data is in PLINK binary format. Calling algorithm for genotypes is based on GenomeStudio (GenTrain), with manual clustering of selected variants.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-04T15:20:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000850","title":"Detection of Clinically Relevant Genetic Variantsin Autism Spectrum Disorderby Whole-Genome Sequencing","description":"Autism Spectrum Disorder (ASD) demonstrates high heritability and familial clustering, yet the genetic causes remain only partially\nunderstood as a result of extensive clinical and genomic heterogeneity. Whole-genome sequencing (WGS) shows promise as a tool\nfor identifying ASD risk genes as well as unreported mutations in known loci, but an assessment of its full utility in an ASD group\nhas not been performed. We used WGS to examine 32 families with ASD to detect de novo or rare inherited genetic variants predicted\nto be deleterious (loss-of-function and damaging missense mutations). Among ASD probands, we identified deleterious de novo muta-\ntions in six of 32 (19%) families and X-linked or autosomal inherited alterations in ten of 32 (31%) families (some had combinations of\nmutations). The proportion of families identified with such putative mutations was larger than has been previously reported; this yield\nwas in part due to the comprehensive and uniform coverage afforded by WGS. Deleterious variants were found in four unrecognized,\nnine known, and eight candidate ASD risk genes. Examples include CAPRIN1 and AFF2 (both linked to FMR1, which is involved in fragile\nX syndrome), VIP (involved in social-cognitive deficits), and other genes such as SCN2A and KCNQ2 (linked to epilepsy), NRXN1, and\nCHD7, which causes ASD-associated CHARGE syndrome. Taken together, these results suggest that WGS and thorough bioinformatic\nanalyses for de novo and rare inherited mutations will improve the detection of genetic variants likely to be associated with ASD or\nits accompanying clinical symptoms.","abstract":"Autism Spectrum Disorder (ASD) demonstrates high heritability and familial clustering, yet the genetic causes remain only partiallyunderstood as a result of extensive clinical and genomic heterogeneity. Whole-genome sequencing (WGS) shows promise as a toolfor identifying ASD risk genes as well as unreported mutations in known loci, but an assessment of its full utility in an ASD grouphas not been performed. We used WGS to examine 32 families with ASD to detect de novo or rare inherited genetic variants predictedto be deleterious (loss-of-function and damaging missense mutations). Among ASD probands, we identified deleterious de novo muta-tions in six of 32 (19%) families and X-linked or autosomal inherited alterations in ten of 32 (31%) families (some had combinations ofmutations). The proportion of families identified with such putative mutations was larger than has been previously reported; this yieldwas in part due to the comprehensive and uniform coverage afforded by WGS. Deleterious variants were found in four unrecognized,nine known, and eight candidate ASD risk genes. Examples include CAPRIN1 and AFF2 (both linked to FMR1, which is involved in fragileX syndrome), VIP (involved in social-cognitive deficits), and other genes such as SCN2A and KCNQ2 (linked to epilepsy), NRXN1, andCHD7, which causes ASD-associated CHARGE syndrome. Taken together, these results suggest that WGS and thorough bioinformaticanalyses for de novo and rare inherited mutations will improve the detection of genetic variants likely to be associated with ASD orits accompanying clinical symptoms.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-04T16:32:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000851","title":"Primary_angiosarcoma_Whole_Genome_Sequencing","description":"Whole genome sequencing of primary angiosarcoma","abstract":"We would like to sequence primary angiosarcoma","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-05T12:34:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000852","title":"Benchmark and validation of whole exome sequencing of a trio and singleton","description":"Whole exome paired-end sequencing data was obtained for a trio and a fourth unrelated individual sequenced to high depth (95x) using a paired-end library with the Illumina HiSeq platform and aligned by BWA 0.5.9. The bam files were analysed and experimentally vaidated for the novel insertion of mobile elements.","abstract":"Whole exome paired-end sequencing data was obtained for a trio and a fourth unrelated individual sequenced to high depth (95x) using a paired-end library with the Illumina HiSeq platform and aligned by BWA 0.5.9. The bam files were analysed and experimentally vaidated for the novel insertion of mobile elements.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-05T12:52:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000853","title":"Whole exome sequencing for gallbladder cancer in Xinhua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine","description":"Patients with gallbladder carcinoma (GBC), the most aggressive malignancy of the biliary tract, have a poor prognosis. Here, we report our identification of somatic mutations of GBCs in 57 tumor-normal pairs by use of a combination of exome sequencing and ultra-deep sequencing of cancer-related genes. The mutation pattern is defined by a dominative prevalence of C&gt;T mutations at TCN sites. Genes with a significant frequency of non-silent mutations include TP53 (47.1%), KRAS (7.8%), and ERBB3 (11.8%). Moreover, ErbB signaling (including EGFR, ERBB2, ERBB3, ERBB4 and their downstream genes) is the most extensively mutated pathway, affecting 36.8% (21 of 57) of the GBC samples. Multivariate analyses further reveal that patients with ErbB pathway mutations have a worse outcome (P = 0.001). These findings provide insight into the somatic mutational landscape in GBC and highlight the key role of the ErbB signaling pathway in the pathogenesis of GBCs.","abstract":"Patients with gallbladder carcinoma (GBC), the most aggressive malignancy of the biliary tract, have a poor prognosis. Here, we report our identification of somatic mutations of GBCs in 57 tumor-normal pairs by use of a combination of exome sequencing and ultra-deep sequencing of cancer-related genes. The mutation pattern is defined by a dominative prevalence of C&gt;T mutations at TCN sites. Genes with a significant frequency of non-silent mutations include TP53 (47.1%), KRAS (7.8%), and ERBB3 (11.8%). Moreover, ErbB signaling (including EGFR, ERBB2, ERBB3, ERBB4 and their downstream genes) is the most extensively mutated pathway, affecting 36.8% (21 of 57) of the GBC samples. Multivariate analyses further reveal that patients with ErbB pathway mutations have a worse outcome (P = 0.001). These findings provide insight into the somatic mutational landscape in GBC and highlight the key role of the ErbB signaling pathway in the pathogenesis of GBCs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-06T03:49:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000854","title":"Systems biology of Colorectal Cancer","description":"Colorectal cancer (CRC) is one of the most common cancers in both males and females, and it is perhaps the best understood of all epithelial tumors in terms of its molecular origin. Yet, despite large amount of work that has concentrated on understanding of colon tumorigenesis, we still do not know the full complement of molecular lesions that are individually necessary – and together sufficient – to cause colorectal cancer. Neither do we understand why some specific mutations that are relatively rare in other tumors (e.g. loss of the APC tumor suppressor) are extremely common in colorectal cancer. We propose here to use the tools of systems biology to develop a quantitative and comprehensive model of colorectal tumorigenesis. The model will include identification of cell-type specific and oncogenic pathways that contribute to colon tumorigenesis, and explain in molecular detail how a genotype of an individual CRC leads to activation of downstream genes that drive uncontrolled cell growth. This model will subsequently be used to find novel therapeutic targets, to guide genetic screening to identify individuals with elevated risk for developing CRC, and to classify patients into molecular subgroups to select the treatment combination that is optimal for each patient (personalized medicine).    The specific objectives of the SYSCOL project are: 1. Identify genetic markers for individual risk using genotyping and sequencing of constitutional DNA from sporadic and familial CRC cases and controls 2. Identify genes and regulatory elements that contribute to colorectal cancer cell growth 3. Use data from Aims 1-2 to develop a quantitative model for colorectal tumorigenesis 4. Apply the model for identification of high-risk individuals, for molecular classification of the disease, and for identification of novel molecular treatment targets","abstract":"Colorectal cancer (CRC) is one of the most common cancers in both males and females, and it is perhaps the best understood of all epithelial tumors in terms of its molecular origin. Yet, despite large amount of work that has concentrated on understanding of colon tumorigenesis, we still do not know the full complement of molecular lesions that are individually necessary – and together sufficient – to cause colorectal cancer. Neither do we understand why some specific mutations that are relatively rare in other tumors (e.g. loss of the APC tumor suppressor) are extremely common in colorectal cancer. We propose here to use the tools of systems biology to develop a quantitative and comprehensive model of colorectal tumorigenesis. The model will include identification of cell-type specific and oncogenic pathways that contribute to colon tumorigenesis, and explain in molecular detail how a genotype of an individual CRC leads to activation of downstream genes that drive uncontrolled cell growth. This model will subsequently be used to find novel therapeutic targets, to guide genetic screening to identify individuals with elevated risk for developing CRC, and to classify patients into molecular subgroups to select the treatment combination that is optimal for each patient (personalized medicine).    The specific objectives of the SYSCOL project are: 1. Identify genetic markers for individual risk using genotyping and sequencing of constitutional DNA from sporadic and familial CRC cases and controls 2. Identify genes and regulatory elements that contribute to colorectal cancer cell growth 3. Use data from Aims 1-2 to develop a quantitative model for colorectal tumorigenesis 4. Apply the model for identification of high-risk individuals, for molecular classification of the disease, and for identification of novel molecular treatment targets","study_type":"Other","pubmed_ids":[25079323],"external_links":null,"is_released":true,"released_date":"2014-06-10T12:50:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000855","title":"Genomic landscape of Ewing sarcoma (ICGC project)","description":"The Ewing sarcoma project aims to sequence 100 complete genomes of cells of patients suffering from this disease. It is an initiative of great projection, since this is the second most common bone tumor in children and teenagers. The goal of the project is to establish the catalogue of somatic mutations that may cooperate with EWS-ETS fusion in the development of the tumor. The Ewing sarcoma project aims to perform 100 whole genome sequencing of germline and tumor DNA as well as at least 50 RNA-seq from tumors. Correlations between molecular profiles and clinical features will be established. The mutated genes will be further validated in a series of 500 Ewing sarcoma cases from our Tumor Bank.","abstract":"The Ewing sarcoma project aims to sequence 100 complete genomes of cells of patients suffering from this disease. It is an initiative of great projection, since this is the second most common bone tumor in children and teenagers. The goal of the project is to establish the catalogue of somatic mutations that may cooperate with EWS-ETS fusion in the development of the tumor. The Ewing sarcoma project aims to perform 100 whole genome sequencing of germline and tumor DNA as well as at least 50 RNA-seq from tumors. Correlations between molecular profiles and clinical features will be established. The mutated genes will be further validated in a series of 500 Ewing sarcoma cases from our Tumor Bank.","study_type":"Other","pubmed_ids":[25223734],"external_links":null,"is_released":true,"released_date":"2014-06-10T16:05:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000856","title":"Neuromics / RD-Connect - leukodystrophy","description":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders. Files available in this study are BAM files from WES of two patients with a new leukodystrophy. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","abstract":"This study contains omics datasets from the Neuromics project (www.rd-neuromics.eu) on rare neuromuscular and neurodegenerative disorders. Files available in this study are BAM files from WES of two patients with a new leukodystrophy. Search under the Neuromics name to find related studies for other neuromuscular and neurodegenerative disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000857","title":"Deep_sequencing_of_melanoma_for_driver_mutations","description":"Deep sequencing of melanoma for driver mutations","abstract":"Although the clinical responses of BRAF mutant melanoma patients to BRAF inhibitors are impressive, the majority of patients relapse after a relatively short period (6-8 months) of disease control. Furthermore, about 20% of patients present with intrinsic or primary resistance and do not respond to BRAF inhibitors despite the presence of a BRAF mutation.  Responses to MEK inhibitors also appear to be limited, with short-term response in some patients and no responses in others. Thus, although targeted agents provide a paradigm shift in the clinical management of melanoma, the responses to these drugs are variable and generally limited.Recent studies have already established that resistance can be mediated by several mechanisms. Although these studies have provided a foundation to our understanding of resistance, it is still not possible to predict cause of primary (intrinsic) and secondary resistance to BRAF inhibitors and a great deal of contemporary melanoma research is focused on understanding the underlying mechanisms. Our primary aim is to determine the causes of resistance to targeted therapies in melanoma patients.  We shall then use this sample to deep sequence the tumor DNA in order to detect mutations that could be pre-existent in the patient and responsible for resistance to the combination Dabrafenib and Trametinib.  This particular patient (C00772) received the combination Dabrafenib + Trametinib for a period of 5 months and presented a partial response. The results of the Whole Exome Sequencing of the resistant sample revealed interesting mutations driving resistance, some of them already published in the literature and some new. We aim to sequence the pre-treated AND post-treated samples and evaluate whether there were clones with these mutations in the pre-treated sample.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-12T11:29:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000858","title":"Integrative_genome_profiling_in_AML","description":"AML emerges as a consequence of accumulating independent genetic aberrations that direct regulation and/or dysfunction of genes resulting in aberrant activation of signalling pathways, resistance to apoptosis and uncontrolled proliferation. Given the significant heterogeneity of AML genomes, AML patients demonstrate a highly variable response rate and poor median survival in response to current chemotherapy regimens. For the past 4 years we have conducted gene expression profiling on purified bone marrow populations equating to normal haematopoietic stem and progenitor cells from healthy subjects and patients with de novo AML in order to identify AML signatures of aberrantly expressed genes in cancer versus normal. We are now applying a series of bioinformatic methodologies combined with clinical and conventional diagnostic data to establish novel genomics strategies for improved prognostication of AML. Additionally, we use our AML signatures to unravel oncogenic signalling pathway activities in AML patients and test inhibitory drugs for these pathways inn preclinical therapeutic programmes. We consider that superimposing GEP and clinical data for our AML patient cohort with additional data on their mutational status will significantly improve the prognostic power of the study as well as unravel yet unknown mutations associated with aberrant signalling activities of oncogenic pathways.","abstract":"AML emerges as a consequence of accumulating independent genetic aberrations that direct regulation and/or dysfunction of genes resulting in aberrant activation of signalling pathways, resistance to apoptosis and uncontrolled proliferation. Given the significant heterogeneity of AML genomes, AML patients demonstrate a highly variable response rate and poor median survival in response to current chemotherapy regimens. For the past 4 years we have conducted gene expression profiling on purified bone marrow populations equating to normal haematopoietic stem and progenitor cells from healthy subjects and patients with de novo AML in order to identify AML signatures of aberrantly expressed genes in cancer versus normal. We are now applying a series of bioinformatic methodologies combined with clinical and conventional diagnostic data to establish novel genomics strategies for improved prognostication of AML. Additionally, we use our AML signatures to unravel oncogenic signalling pathway activities in AML patients and test inhibitory drugs for these pathways inn preclinical therapeutic programmes. We consider that superimposing GEP and clinical data for our AML patient cohort with additional data on their mutational status will significantly improve the prognostic power of the study as well as unravel yet unknown mutations associated with aberrant signalling activities of oncogenic pathways.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-12T11:43:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000859","title":"Anaplastic_Meningioma_WGS_X10","description":"Anaplastic meningiomas are a rare, malignant variant of meningioma. At present there is no effective treatment for this cancer. The aim of the study is to identify somatic mutations in anaplastic meningiomas. We plan to sequence a set of 500 known cancer genes in 50 anaplastic meningioma and corresponding peripheral blood DNA samples. Bioinformatics will be used to analyse the results to assess the probability of these mutations being causal and so likely of critical importance for the tumour growth. Identification of these mutations will guide selection of appropriate compounds to effectively treat the disease.","abstract":"Anaplastic meningiomas are a rare, malignant variant of meningioma. At present there is no effective treatment for this cancer. The aim of the study is to identify somatic mutations in anaplastic meningiomas. We plan to sequence a set of 500 known cancer genes in 50 anaplastic meningioma and corresponding peripheral blood DNA samples. Bioinformatics will be used to analyse the results to assess the probability of these mutations being causal and so likely of critical importance for the tumour growth. Identification of these mutations will guide selection of appropriate compounds to effectively treat the disease.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-12T13:19:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000860","title":"Use_of_deep_sequencing_to_detect_clonal_mutations_in_sun_exposed_human_epidermis___whole_genome","description":"Deep sequencing of two skin biopsies to study the landscape of somatic mutations in human adult tissues.","abstract":"Deep sequencing of two skin biopsies to study the landscape of somatic mutations in human adult tissues.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-12T13:30:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000861","title":"UK Inflammatory Bowel Disease Genetics Consortium Immunochip","description":"The International Inflammatory Bowel Disease Genetics Consortium has analyzed data from the Immunochip platform (200,000 SNPs focused on regions of the genome previously implicated, or suggestively associated with immune and inflammatory disease) on over 40,000 individuals (including cases of Crohn's disease, ulcerative colitis, and controls). This data release represents the component of that study generated by the UK IBD Genetics Consortium.","abstract":"The International Inflammatory Bowel Disease Genetics Consortium has analyzed data from the Immunochip platform (200,000 SNPs focused on regions of the genome previously implicated, or suggestively associated with immune and inflammatory disease) on over 40,000 individuals (including cases of Crohn's disease, ulcerative colitis, and controls). This data release represents the component of that study generated by the UK IBD Genetics Consortium.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000862","title":"Genome_Diversity_in_Africa_Project","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region.The African Genome Variation Project (AGVP) is an international collaboration that aims to produce a comprehensive catalogue of human genetic variation in SSA. This resource has extended our understanding of population history, patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies.The Genome Diversity in Africa Project (GDAP) will extend and expand the African Genome Variation (AGV) project. Using a sequencing-based approach, GDA project aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out low coverage (4x) whole genome sequencing of up to 2000 individuals across Africa (100 individuals from each ethnolinguistic group), and complement these data with 2.5M Illumina genotyping. We have already completed sequencing of 700 individuals across SSA, we are now adding an additional 500 samples from up to 5 ethno-linguistic groups within Africa, including populations from Burkina Faso, Cameroon, Morocco, Ghana and Seychelles.Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics.","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out low coverage (4x) whole genome sequencing of up to 2000 individuals across Africa (100 individuals from each ethnolinguistic group), and complement these data with 2.5M Illumina genotyping. We have already completed sequencing of 700 individuals across SSA, we are now adding an additional 500 samples from up to 5 ethno-linguistic groups within Africa, including populations from Burkina Faso, Cameroon, Morocco, Ghana and Seychelles.Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000863","title":"Genome_Diversity_in_Africa_Project","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region.The African Genome Variation Project (AGVP) is an international collaboration that aims to produce a comprehensive catalogue of human genetic variation in SSA. This resource has extended our understanding of population history, patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies.The Genome Diversity in Africa Project (GDAP) will extend and expand the African Genome Variation (AGV) project. Using a sequencing-based approach, GDA project aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out low coverage (4x) whole genome sequencing of up to 2000 individuals across Africa (100 individuals from each ethnolinguistic group), and complement these data with 2.5M Illumina genotyping. We have already completed sequencing of 700 individuals across SSA, we are now adding an additional 500 samples from up to 5 ethno-linguistic groups within Africa, including populations from Burkina Faso, Cameroon, Morocco, Ghana and Seychelles.Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics.","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out low coverage (4x) whole genome sequencing of up to 2000 individuals across Africa (100 individuals from each ethnolinguistic group), and complement these data with 2.5M Illumina genotyping. We have already completed sequencing of 700 individuals across SSA, we are now adding an additional 500 samples from up to 5 ethno-linguistic groups within Africa, including populations from Burkina Faso, Cameroon, Morocco, Ghana and Seychelles.Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000864","title":"The_life_history_of_colorectal_cancer_metastases_study_WGS_X10","description":"Whole genome sequencing of a series of metastasis collected from 2 patients at autopsy will be used to construct a life history of the cancer, including phylogenetic relationship between the different metastases an also whether there is evidence of convergence towards common biological processes that underpin the metastatic process but though different mutational events","abstract":"Whole genome sequencing of a series of metastasis collected from 2 patients at autopsy will be used to construct a life history of the cancer, including phylogenetic relationship between the different metastases an also whether there is evidence of convergence towards common biological processes that underpin the metastatic process but though different mutational events","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-18T09:21:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000865","title":"HipSci_Illumina 450K Methylation analysis_Healthy volunteers","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium HumanMethylation450 BeadChip on iPS cells generated from skin biopsies from healthy volunteers.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium HumanMethylation450 BeadChip on iPS cells generated from skin biopsies from healthy volunteers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-18T09:47:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000866","title":"HipSci HumanExome BeadChip analysis-Healthy volunteers","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies from healthy volunteers.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies from healthy volunteers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-18T09:58:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000867","title":"HipSci HumanHT_12v4 Expression BeadChip analysis-Healthy volunteers","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies from healthy volunteers.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies from healthy volunteers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-18T10:51:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000868","title":"Targeted_gene_screens_in_Diffuse_Large_B_cell_Lymphoma___a_pilot_with_the_The_Haematological_Malignancy_Research_Network__HMRN_","description":"14M Genomics will undertake next-generation sequencing (NGS) of clinical samples usingexisting infrastructure and personnel at the Wellcome Trust Sanger Institute (WTSI). Theability to commence operations using existing infrastructure, personnel and expertise withinthe WTSI will accelerate the ability of the company to transition to an independent facility. Itwill also enable the company to commence sequencing, in an established environment, a setof samples that will test specific technical and diagnostic issues critical to the success of thecompany (the ‘Pilot’). These will be comprised mostly of a cohort of 1,500 DLBCL samplesfrom the Haematological Malignancy Research Network (HMRN) in the Leeds/York. HMRNwas established in 2004 to collect detailed clinical information about all haematologicalmalignancies diagnosed between two adjacent UK Cancer Networks; the Yorkshire CancerNetwork and the Humber &amp; Yorkshire Coast Cancer Network. HMRN has full ethical approvalto collect clinical data for audit and research. They are thus ideally placed to collaborate with14M Genomics to sequence this cohort of approx. 1,500 tumour samples selected tospecifically address technical and diagnostic issues","abstract":"14M Genomics will undertake next-generation sequencing (NGS) of clinical samples usingexisting infrastructure and personnel at the Wellcome Trust Sanger Institute (WTSI). Theability to commence operations using existing infrastructure, personnel and expertise withinthe WTSI will accelerate the ability of the company to transition to an independent facility. Itwill also enable the company to commence sequencing, in an established environment, a setof samples that will test specific technical and diagnostic issues critical to the success of thecompany (the ‘Pilot’). These will be comprised mostly of a cohort of 1,500 DLBCL samplesfrom the Haematological Malignancy Research Network (HMRN) in the Leeds/York. HMRNwas established in 2004 to collect detailed clinical information about all haematologicalmalignancies diagnosed between two adjacent UK Cancer Networks; the Yorkshire CancerNetwork and the Humber &amp; Yorkshire Coast Cancer Network. HMRN has full ethical approvalto collect clinical data for audit and research. They are thus ideally placed to collaborate with14M Genomics to sequence this cohort of approx. 1,500 tumour samples selected tospecifically address technical and diagnostic issues","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000869","title":"Colorectal_organoids_and_tumoroids___pulldown","description":"Targeted capture of cancer gene panel bait set in single cell derived organoids from colon tissue and colorectal cancer from 1 patient.","abstract":"This study aims to describe the driver landscape in normal colorectal tissue and tumour.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-25T10:27:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000870","title":"BLUEPRINT EpiVar ChIP-seq of Monocytes & Neutrophils","description":"BLUEPRINT EpiVar ChIP-seq of Monocytes &amp; Neutrophils","abstract":"BLUEPRINT EpiVar ChIP-seq of Monocytes &amp; Neutrophils","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-25T13:09:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000871","title":"Chugai_colorectal_organoid_sequencing","description":"Genomic and transcriptomic characterization of drug-resistant colon cancer stem cell lines.","abstract":"Almost half of all colon cancer patients succumb to drug-resistant metastatic disease. There is some evidence that in part this may be due to the survival of colon cancer stem cells in a drug-resistant niche within the tumour population. Therefore, there is increasing interest in reversing this drug resistance. In the past this has been hampered by a paucity of biological models that faithfully recapitulated the colon stem cell state.1. Chugai Pharmaceuticals have established 2 colon cancer stem cell (CSC) lines that are capable of tumour reconstitution as xenografts in NOD/scid mice,2. CSCs are positive for Lgr5, which is a marker of stem cells in the intestine and in human colon cancer,3. Upon exposure to irinotecan (a drug commonly used in colon cancer), CSCs undergo a poorly understood reversible conversion to a drug-resistant Lgr5 negative state.We propose to characterise the drug-resistant state of these cancer stem cells through a combination of high-throughput small molecule inhibitor drug screens as well as whole exome sequence, copy number analysis, mRNA gene expression and methylation.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000872","title":"Chugai_colorectal_organoid_sequencing","description":"Genomic and transcriptomic characterization of drug-resistant colon cancer stem cell lines.","abstract":"Almost half of all colon cancer patients succumb to drug-resistant metastatic disease. There is some evidence that in part this may be due to the survival of colon cancer stem cells in a drug-resistant niche within the tumour population. Therefore, there is increasing interest in reversing this drug resistance. In the past this has been hampered by a paucity of biological models that faithfully recapitulated the colon stem cell state.1. Chugai Pharmaceuticals have established 2 colon cancer stem cell (CSC) lines that are capable of tumour reconstitution as xenografts in NOD/scid mice,2. CSCs are positive for Lgr5, which is a marker of stem cells in the intestine and in humancolon cancer,3. Upon exposure to irinotecan (a drug commonly used in colon cancer), CSCs undergo a poorly understood reversible conversion to a drug-resistant Lgr5 negative state.We propose to characterise the drug-resistant state of these cancer stem cells through a combination of high-throughput small molecule inhibitor drug screens as well as whole exome sequence, copy number analysis, mRNA gene expression and methylation.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-06-26T13:18:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000873","title":"TBA","description":"Analysis of mutational signatures caused by DNA repair defects in human induced pluripotent stem (iPS) cells. A reference human iPS cell line will be used for genetic manipulation to introduce homozygous knockouts of 100 genes known to be involved in or connected to DNA repair or DNA editing. Following a defined period of growth after homozygous knockout of each gene, sub clones will be generated and sequenced. The progenitor “parental” IPS cell line will be used to generate reference sequence data, in order to determine the mutational signature acquired due to the gene knockout.This is a pilot study to investigate the effects of oxygen conditions and growth period on mutations acquired","abstract":"Analysis of mutational signatures caused by DNA repair defects in human induced pluripotent stem (iPS) cells. A reference human iPS cell line will be used for genetic manipulation to introduce homozygous knockouts of 100 genes known to be involved in or connected to DNA repair or DNA editing. Following a defined period of growth after homozygous knockout of each gene, sub clones will be generated and sequenced. The progenitor “parental” IPS cell line will be used to generate reference sequence data, in order to determine the mutational signature acquired due to the gene knockout.This is a pilot study to investigate the effects of oxygen conditions and growth period on mutations acquired","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000874","title":"Guardians_of_the_genome__protecting_DNA_from_endogenous_sources_of_damage_","description":"Analysis of mutational signatures caused by DNA repair defects in human induced pluripotent stem (iPS) cells. A reference human iPS cell line will be used for genetic manipulation to introduce homozygous knockouts of 100 genes known to be involved in or connected to DNA repair or DNA editing. Following a defined period of growth after homozygous knockout of each gene, sub clones will be generated and sequenced. The progenitor “parental” IPS cell line will be used to generate reference sequence data, in order to determine the mutational signature acquired due to the gene knockout. This is a pilot study to investigate the effects of oxygen conditions and growth period on mutations acquired","abstract":"Mutational signatures are imprints of cell-intrinsic and extrinsic pathophysiological processes that have occurred through tumorigenesis. Experimental efforts to explore signature etiologies have produced a compendium of signatures of exogenous mutagens previously. Here, we unearth major sources of endogenous DNA damage and the genes that are critical to mitigating this innate stream of DNA damage under normal, physiological circumstances. We performed whole genome sequencing of 173 subclones of CRISPR-Cas9 knockouts of 43 genes in a human induced pluripotent stem cell system, in the absence of any added DNA damage. We reveal substitution and indel signatures that arise from those genes which are essential guardians of the genome. By detailed dissection and comparisons to cancer-derived signatures, we demonstrate interminable sources of constitutive DNA damage, and some mechanistic knowledge into how guardian genes preserve the genome. Based on these experimental insights, we develop and benchmark a tool for clinical classification of tumor samples.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-01T15:26:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000875","title":"Loss of functional mutation in RPL27 and RPS27 identified by whole-exome sequencing in Diamond-Blackfan Anemia","description":"We performed whole-exome sequencing analysis of 48 patients with no documented mutations/deletions involving known Diamond-Blackfan anemia genes and identified 10 mutations in previous known causative genes and 2 mutations in novel ribosomal genes.","abstract":"We performed whole-exome sequencing analysis of 48 patients with no documented mutations/deletions involving known Diamond-Blackfan anemia genes and identified 10 mutations in previous known causative genes and 2 mutations in novel ribosomal genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-02T07:15:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000876","title":"Characterization_of_iPSC_derived_macrophages___cardiovascular_pilot","description":"This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The goal of this experiment is to understand the transcriptional changes occuring in macrophages during exposure to modfied low-density lipoprotein (LDL), a causal risk factor for coronary heart disease.We will be using macrophages derived from induced pluripotent stem cells from several donors to characterize early (~8h) and late (~24h) changes in the transcriptional profile after exposure to modified LDL.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-02T10:45:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000877","title":"Whole genome DNA sequencing for two long-lived humans.","description":"Two long-lived human samples were sequenced to a mean 20x coverage genome wide.  Sequencing was done using the Illumina hi-seq platform, alignment to GRCh37/hg19 reference genome was done using the BWA alignment tool.","abstract":"Two long-lived human samples were sequenced to a mean 20x coverage genome wide.  Sequencing was done using the Illumina hi-seq platform, alignment to GRCh37/hg19 reference genome was done using the BWA alignment tool.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-02T11:45:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000878","title":"Genome-wide SNP and CNV analysis identifies common and low-frequency variants associated with severe early-onset obesity","description":"We performed SNP and copy number variation (CNV) association analyses in 1,509 children with obesity at the extreme tail (&gt;3 s.d. from the mean) of the BMI distribution and 5,380 controls. The control samples were made available from the EGA with accession numbers EGAD00000000021 and EGAD00000000023.","abstract":"We performed SNP and copy number variation (CNV) association analyses in 1,509 children with obesity at the extreme tail (&gt;3 s.d. from the mean) of the BMI distribution and 5,380 controls. The control samples were made available from the EGA with accession numbers EGAD00000000021 and EGAD00000000023.","study_type":"Other","pubmed_ids":[23563609],"external_links":null,"is_released":true,"released_date":"2014-07-03T14:07:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000879","title":"Prognostic_factors_in_prostate_cancer__deep_sequencing_pilot_project_TAPG","description":"This is a pilot project to determine whether the TAPG FFPE DNA’s are suitable for deep sequencing. If successful an investigation of SNP distribution in a larger cohort will follow.","abstract":"This is a pilot project to determine whether the TAPG FFPE DNA’s are suitable for deep sequencing. If successful an investigation of SNP distribution in a larger cohort will follow.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-03T14:38:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000880","title":"Myeloma_Targeted_Follow_up_Study","description":"390 samples, perform WGA, and send the WGA’d DNA to core for pre-capture library and tagging, pulldown with ELID 631172 (16 samples per reaction tube), and sequencing (24 samples per lane)","abstract":"390 samples, perform WGA, and send the WGA’d DNA to core for pre-capture library and tagging, pulldown with ELID 631172 (16 samples per reaction tube), and sequencing (24 samples per lane)","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-03T15:19:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000881","title":"Colorectal_organoids_and_tumour_tissue","description":"Whole genome sequencing of single cell derived organoids from normal colon tissue and colorectal cancer.","abstract":"This study aims to describe mutational processes in colorectal cancer and adjacent normal tissue.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-03T15:28:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000882","title":"Succession Of Transiently Active Tumour-Initiating Cell Clones inHuman Pancreatic Cancer","description":"To elucidate whether newly acquired genetic alterations during serial transplantation of patient derived primary pancreatic cancer cultures contribute to the observed clonal dynamics in vivo, all coding genes of two  patient derived primary cultures and derived genetically marked serial xenografts (1°/2°/3°) were sequenced.","abstract":"To elucidate whether newly acquired genetic alterations during serial transplantation of patient derived primary pancreatic cancer cultures contribute to the observed clonal dynamics in vivo, all coding genes of two  patient derived primary cultures and derived genetically marked serial xenografts (1°/2°/3°) were sequenced.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-07T11:44:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000883","title":"Study on the proliferation history of colorectal adenomas","description":"Mismatch repair (MMR) deficient colorectal adenomas are composed of transformed cells that descend from a common founder and progressively accumulate genomic alterations but their proliferation history is still largely unknown. Here we rebuilt the proliferation history of four MMR deficient colorectal adenomas from male individuals by deep sequencing the X chromosome and mapping the somatic mutations that were progressively acquired during tumor growth. We developed a novel method to call high and low frequency mutations, to cluster them according to their frequencies and rebuild the proliferation trees directly from these mutation clusters using a recursive algorithm. The trees of all four lesions were formed of a dominant subclone that coexisted with other genetically heterogeneous subpopulations of cells. Despite this similar hierarchical organization, however, the growth dynamics varied among and within tumors, likely depending on a combination of tumor-specific genetic and environmental factors. Our study provides insights into the biological properties of individual MMR deficient colorectal adenomas that may influence their growth and also the response to therapy. Extended to other solid tumors, our approach could inform on the mechanisms of cancer progression, thus providing insight into the best choice of cancer treatment methods.","abstract":"Mismatch repair (MMR) deficient colorectal adenomas are composed of transformed cells that descend from a common founder and progressively accumulate genomic alterations but their proliferation history is still largely unknown. Here we rebuilt the proliferation history of four MMR deficient colorectal adenomas from male individuals by deep sequencing the X chromosome and mapping the somatic mutations that were progressively acquired during tumor growth. We developed a novel method to call high and low frequency mutations, to cluster them according to their frequencies and rebuild the proliferation trees directly from these mutation clusters using a recursive algorithm. The trees of all four lesions were formed of a dominant subclone that coexisted with other genetically heterogeneous subpopulations of cells. Despite this similar hierarchical organization, however, the growth dynamics varied among and within tumors, likely depending on a combination of tumor-specific genetic and environmental factors. Our study provides insights into the biological properties of individual MMR deficient colorectal adenomas that may influence their growth and also the response to therapy. Extended to other solid tumors, our approach could inform on the mechanisms of cancer progression, thus providing insight into the best choice of cancer treatment methods.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-07T17:10:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000884","title":"Integrated genetic and epigenetic analysis defines novel molecular clusters in rhabdomyosarcoma","description":"Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood. To unravel the genetic/epigenetic basis of RMS, we studied 60 RMS cases using whole exome/transcriptome sequencing, copy number (CN) profiling, and DNA methylome analysis. Based on DNA methylation patterns, RMS was clustered into 4 distinct subtypes, which exhibited remarkable correlation with mutation/CN profiles, histological phenotypes, and clinical behaviors. A1 and A2 subtypes, especially A1, largely corresponded to alveolar histology with frequent PAX3/7 fusions and alterations in cell cycle regulators. In contrast, mostly showing embryonal histology, both E1 and E2 subtypes were characterized by high frequency of CN alterations and/or allelic imbalances, FGFR4/RAS/AKT pathway mutations and PTEN mutations/methylation and in E2, also by p53 inactivation. Despite generally poor prognosis in RMS, patients in E1 cluster exceptionally showed excellent prognosis. Our results highlight the close relationship between DNA methylation status and gene mutations and biological behavior in RMS.","abstract":"Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood. To unravel the genetic/epigenetic basis of RMS, we studied 60 RMS cases using whole exome/transcriptome sequencing, copy number (CN) profiling, and DNA methylome analysis. Based on DNA methylation patterns, RMS was clustered into 4 distinct subtypes, which exhibited remarkable correlation with mutation/CN profiles, histological phenotypes, and clinical behaviors. A1 and A2 subtypes, especially A1, largely corresponded to alveolar histology with frequent PAX3/7 fusions and alterations in cell cycle regulators. In contrast, mostly showing embryonal histology, both E1 and E2 subtypes were characterized by high frequency of CN alterations and/or allelic imbalances, FGFR4/RAS/AKT pathway mutations and PTEN mutations/methylation and in E2, also by p53 inactivation. Despite generally poor prognosis in RMS, patients in E1 cluster exceptionally showed excellent prognosis. Our results highlight the close relationship between DNA methylation status and gene mutations and biological behavior in RMS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-08T12:24:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000885","title":"Whole Genome Sequencing to track subclonal heterogeneity in 18  samples from 3 Chronic Lymphocytic Leukemia patients subjected to repeated cycles of therapy.","description":"This study took 18 samples from three patients with Chronic Lymphocytic Leukemia. The 3 CLL patients received multiple different treatments sequentially for a period of up to 7 years. Peripheral blood samples were taken at 5 specific time points during disease progression together with 1 matched buccal swab per patient.  All the selected patients had unmutated IgVH status reflecting poor prognosis. However, none of the patients had complex genomic aberrations associated with aggressive disease.   Peripheral blood samples and buccal smears were obtained from patients, who had given informed consent for sequential sample collection and analysis. Tumour samples were obtained before treatment, after treatment and at relapse and subjected to Ficoll separation. Lymphocyte cell purity was assessed by full blood count enumeration. Buccal smears were obtained and processed using Isohelix.","abstract":"This study took 18 samples from three patients with Chronic Lymphocytic Leukemia. The 3 CLL patients received multiple different treatments sequentially for a period of up to 7 years. Peripheral blood samples were taken at 5 specific time points during disease progression together with 1 matched buccal swab per patient.  All the selected patients had unmutated IgVH status reflecting poor prognosis. However, none of the patients had complex genomic aberrations associated with aggressive disease.   Peripheral blood samples and buccal smears were obtained from patients, who had given informed consent for sequential sample collection and analysis. Tumour samples were obtained before treatment, after treatment and at relapse and subjected to Ficoll separation. Lymphocyte cell purity was assessed by full blood count enumeration. Buccal smears were obtained and processed using Isohelix.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-08T16:09:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000886","title":"WTCCC2 Reading and Mathematics (RM) samples","description":"A WTCCC2 project genome-wide association study for reading and mathematics ability in 3665 12-year-old individuals from the UK, genotyped on the Affymetrix 6.0 array. Details of the WTCCC2 analysis can be found in Davis et al. [Nat. Commun. 2014 July;5:4204]","abstract":"A WTCCC2 project genome-wide association study for reading and mathematics ability in 3665 12-year-old individuals from the UK, genotyped on the Affymetrix 6.0 array. Details of the WTCCC2 analysis can be found in Davis et al. [Nat. Commun. 2014 July;5:4204]","study_type":"Other","pubmed_ids":[25003214],"external_links":null,"is_released":true,"released_date":"2014-07-10T14:54:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000887","title":"Subclonal diversification of primary breast cancer","description":"Cancers are ecosystems of genetically related clones, competing across space and time for limited resources. To understand the clonal structure of primary breast cancer, we applied genome and targeted sequencing to 295 samples from 49 patients’ tumors. The extent of subclonal diversification varied considerably among patients and encompassed many spatial patterns, including local growth, intraductal dissemination and clonal intermixture. Landmarks of disease progression, such as acquiring invasive or metastatic potential, arose within detectable subclones of antecedent lesions, suggesting that subclonal mutations could be relevant if actionable. No defined temporal order of mutation was evident, with the commonest genes, including PIK3CA, TP53, BRCA2, PTEN and MYC, mutated early in some, late in others, often exhibiting parallel evolution across subclones. Signatures of homologous recombination deficiency correlated with response to neoadjuvant chemotherapy. Thus, the interplay of mutation, growth and competition drives clonal structures of breast cancer that are complex, variable across patients and clinically relevant.","abstract":"Cancers are ecosystems of genetically related clones, competing across space and time for limited resources. To understand the clonal structure of primary breast cancer, we applied genome and targeted sequencing to 295 samples from 49 patients’ tumors. The extent of subclonal diversification varied considerably among patients and encompassed many spatial patterns, including local growth, intraductal dissemination and clonal intermixture. Landmarks of disease progression, such as acquiring invasive or metastatic potential, arose within detectable subclones of antecedent lesions, suggesting that subclonal mutations could be relevant if actionable. No defined temporal order of mutation was evident, with the commonest genes, including PIK3CA, TP53, BRCA2, PTEN and MYC, mutated early in some, late in others, often exhibiting parallel evolution across subclones. Signatures of homologous recombination deficiency correlated with response to neoadjuvant chemotherapy. Thus, the interplay of mutation, growth and competition drives clonal structures of breast cancer that are complex, variable across patients and clinically relevant.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000888","title":"65 prostate cancer cases WGS and transcriptome sequencing project","description":"We obtained whole-genome and transcriptome sequencing of tumor-benign pairs from 65 Asian prostate cancer (PCa) patients. Taken together with the TCGA PCa cohort, our integration analysis provides the first comprehensive mutational landscape of PCas across major ethnics worldwide and reveals potential novel role of frequent altered chromatin remodeler genes in PCas without androgen receptor (AR) alteration and complex rearrangements derived from Chromoplexy. In addition, we identified 5 putative tumor suppressor genes (TSGs) chains including one on chromosome 13q with novel findings of PCDH9 (deletions in 15/65 tumors) which was implicated in aggressive progression of prostate cancer. Finally, the integrative pathway and co-expression network analysis followed by the functional study indicated the frequent altered genes, particularly focal amplifications of PLXNA1 (11/65), in semaphoring signaling of axon guidance pathway may interact with PI3K/AKT and AR signaling and also contribute to the aggressiveness and progression of prostate cancer.","abstract":"We obtained whole-genome and transcriptome sequencing of tumor-benign pairs from 65 Asian prostate cancer (PCa) patients. Taken together with the TCGA PCa cohort, our integration analysis provides the first comprehensive mutational landscape of PCas across major ethnics worldwide and reveals potential novel role of frequent altered chromatin remodeler genes in PCas without androgen receptor (AR) alteration and complex rearrangements derived from Chromoplexy. In addition, we identified 5 putative tumor suppressor genes (TSGs) chains including one on chromosome 13q with novel findings of PCDH9 (deletions in 15/65 tumors) which was implicated in aggressive progression of prostate cancer. Finally, the integrative pathway and co-expression network analysis followed by the functional study indicated the frequent altered genes, particularly focal amplifications of PLXNA1 (11/65), in semaphoring signaling of axon guidance pathway may interact with PI3K/AKT and AR signaling and also contribute to the aggressiveness and progression of prostate cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-16T09:33:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000889","title":"TEST_STUDY for submitter testing","description":"This is a test study for the purpose of submitters wishing to test the EGA submission procedure.  All objects, such as DAC and datasets, linked to this study can also be considered to be for testing purposes.","abstract":"This is a test study for the purpose of submitters wishing to test the EGA submission procedure.  All objects, such as DAC and datasets, linked to this study can also be considered to be for testing purposes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-21T13:26:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000890","title":"Multisite_Breast_Cancer_Whole_Genome","description":"DNA extracted from multiple biopsies taken from different areas of primary breast tumours will be subjected to whole genome sequencing and analysed in order to assess intra-tumour heterogeneity with respect to mutations.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-04T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000891","title":"Multisite_Primary_Breast_Cancer","description":"DNA extracted from multiple biopsies taken from different areas of primary breast tumours will be subjected to targeted re-sequencing and analysed in order to assess intra-tumour heterogeneity with respect to mutations in a selection of cancer related genes.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-21T15:05:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000892","title":"Chordoma_Extension_Study","description":"Extension analysis to pursue candidate genes of interest in chordoma","abstract":"Investigation of candidate genes in chordoma","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-23T08:54:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000893","title":"MEF_Spontaneous_Mutation","description":"This study is to look at the effect of oxygen conditions on spontaneous mutation signatures observed in wild type and Hupki mouse embryonic fibroblasts (MEFs).","abstract":"This study is to look at the effect of oxygen conditions on spontaneous mutation signatures observed in wild type and Hupki mouse embryonic fibroblasts (MEFs).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000894","title":"Helleday_MYC","description":"This study is to look at the effect of Myc and oxygen conditions on mutational signatures, to help establish causative roles for particular signatures.","abstract":"This study is to look at the effect of Myc and oxygen conditions on mutational signatures, to help establish causative roles for particular signatures.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000895","title":"Chordoma_Extension__known_cancer_genes_","description":"Extension analysis to pursue candidate genes of interest in chordoma","abstract":"Investigation of known cancer genes in chordoma","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-23T08:57:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000896","title":"An isolated cohort of samples from the Greek island of Crete that have been genotyped on the Illumina CoreExome array.","description":"Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies.  Here we have genotyped individuals from a Greek population isolate on the Illumina CoreExome Beadchip. The HELIC (Hellenic Isolated Cohorts) MANOLIS (Minoan Isolates) collection focuses on Anogia and surrounding Mylopotamos villages.  Recruitment of this population-based sample was primarily carried out at the village medical centres. All individuals were older than 17 years and had to have at least one parent from the Mylopotamos area. www.helic.org","abstract":"Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies.  Here we have genotyped individuals from a Greek population isolate on the Illumina CoreExome Beadchip. The HELIC (Hellenic Isolated Cohorts) MANOLIS (Minoan Isolates) collection focuses on Anogia and surrounding Mylopotamos villages.  Recruitment of this population-based sample was primarily carried out at the village medical centres. All individuals were older than 17 years and had to have at least one parent from the Mylopotamos area. www.helic.org","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-23T10:12:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000897","title":"Illumina Human CoreExome genotype data from the Pomak villages in Greece (HELIC Pomak Isolate). All >=16 years old.","description":"Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies.  Here we have genotyped individuals from a Greek population isolate on the Illumina CoreExome Beadchip. The HELIC (Hellenic Isolated Cohorts) Pomak collection focuses on the Pomak villages in Greece.  Recruitment of this population-based sample was primarily carried out at the village medical centres (www.helic.org)","abstract":"Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies.  Here we have genotyped individuals from a Greek population isolate on the Illumina CoreExome Beadchip. The HELIC (Hellenic Isolated Cohorts) Pomak collection focuses on the Pomak villages in Greece.  Recruitment of this population-based sample was primarily carried out at the village medical centres (www.helic.org)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000898","title":"North Indian Coealic Disease Immunochip Study","description":"Illumina Immunochip genotype data for 247 coeliac disease cases and 736 control samples of the North Indian origin. Data is in PLINK binary format. Calling algorithm for genotypes is based on GenomeStudio (GenTrain), with manual clustering of selected variants (please see published manuscript).  We sought to better understand how disease-associated loci that have been mapped in Europeans translate to a disease risk for a population with a different ethnic background, such as North Indian. We performed a validation of European risk loci for coeliac disease (CeD) in 497 cases and 736 controls. Using a dense-genotyping platform (Immunochip), we confirmed the strong association to the HLA region. Three loci showed suggestive association. We directly replicated five previously reported European variants. The north Indian population has a higher degree of consanguinity than Europeans and we therefore explored the role of recessively acting variants, which replicated the HLA locus and suggested a role of additional four loci.","abstract":"Illumina Immunochip genotype data for 247 coeliac disease cases and 736 control samples of the North Indian origin. Data is in PLINK binary format. Calling algorithm for genotypes is based on GenomeStudio (GenTrain), with manual clustering of selected variants (please see published manuscript).  We sought to better understand how disease-associated loci that have been mapped in Europeans translate to a disease risk for a population with a different ethnic background, such as North Indian. We performed a validation of European risk loci for coeliac disease (CeD) in 497 cases and 736 controls. Using a dense-genotyping platform (Immunochip), we confirmed the strong association to the HLA region. Three loci showed suggestive association. We directly replicated five previously reported European variants. The north Indian population has a higher degree of consanguinity than Europeans and we therefore explored the role of recessively acting variants, which replicated the HLA locus and suggested a role of additional four loci.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000899","title":"SeqControl: Process Control for DNA Sequencing","description":"As next-generation sequencing (NGS) continues to increase in speed and throughput, routine clinical and industrial application draws steadily closer. These “production” uses of NGS will require enhanced quality-monitoring and quality-control to optimize output and reduce costs. We therefore developed a framework called SeqControl for predicting sequencing quality and coverage using a set of 15 metrics describing overall coverage, coverage distribution, base-wise coverage and base-wise quality. Using whole-genome sequences of 27 prostate cancers and 26 normal references we derive multivariate models that predict sequencing quality and depth. SeqControl robustly predicts how much sequencing is required to reach a given coverage depth (AUC = 0.993), accurately classifies clinically relevant formalin-fixed paraffin-embedded samples and makes predictions from as little as 1/8 of a lane of sequencing data (AUC = 0.967). These techniques can be immediately incorporated into existing NGS pipelines to monitor data quality in real-time. SeqControl represents a first step towards statistical process-control for NGS.","abstract":"As next-generation sequencing (NGS) continues to increase in speed and throughput, routine clinical and industrial application draws steadily closer. These “production” uses of NGS will require enhanced quality-monitoring and quality-control to optimize output and reduce costs. We therefore developed a framework called SeqControl for predicting sequencing quality and coverage using a set of 15 metrics describing overall coverage, coverage distribution, base-wise coverage and base-wise quality. Using whole-genome sequences of 27 prostate cancers and 26 normal references we derive multivariate models that predict sequencing quality and depth. SeqControl robustly predicts how much sequencing is required to reach a given coverage depth (AUC = 0.993), accurately classifies clinically relevant formalin-fixed paraffin-embedded samples and makes predictions from as little as 1/8 of a lane of sequencing data (AUC = 0.967). These techniques can be immediately incorporated into existing NGS pipelines to monitor data quality in real-time. SeqControl represents a first step towards statistical process-control for NGS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-23T13:44:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000900","title":"Canadian Prostate Cancer Genome Network","description":"Over 5 years, CPC-GENE will sequence the genomes of 350 intermediate risk prostate cancers to identify genetic signatures that differ in cancers that responded well to treatment compared with those that did not.  CPC-GENE will also sequence multiple regions of prostate cancer from the same gland to determine if and how the genetic make-up of prostate cancer varies within an individual man’s prostate","abstract":"Over 5 years, CPC-GENE will sequence the genomes of 350 intermediate risk prostate cancers to identify genetic signatures that differ in cancers that responded well to treatment compared with those that did not.  CPC-GENE will also sequence multiple regions of prostate cancer from the same gland to determine if and how the genetic make-up of prostate cancer varies within an individual man’s prostate","study_type":"Other","pubmed_ids":[28068672],"external_links":null,"is_released":true,"released_date":"2014-07-23T14:04:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000901","title":"The Genomic Landscape of Childhood and Adolescent Melanoma","description":"Despite remarkable advances in the genomic characterization of adult melanoma, the molecular pathogenesis of pediatric melanoma remains largely unknown. We analyzed 15 conventional melanomas (CM), 3 melanomas arising in congenital nevi (CNM), and 5 spitzoid melanomas (SM), using various platforms, including whole genome or exome sequencing, molecular inversion probe assay, and/or targeted sequencing. CM demonstrated a high burden of somatic single nucleotide variations (SNV), with each case containing a TERT promoter (TERT-p) mutation, 13/15 containing an activating BRAF V600 mutation, and &gt;80% of the identified SNV consistent with UV damage. By contrast, the 3 CNM contained an activating NRAS Q61 mutation and no TERT-p mutations. SM were characterized by chromosomal rearrangements resulting in activated kinase signaling in 40%, and an absence of TERT-p mutations except for the one SM that succumbed to hematogenous metastasis. We conclude that pediatric CM has a very similar UV-induced mutational spectrum to that found in the adult counterpart, emphasizing the need to promote sun protection practices in early life and to improve access to therapeutic agents being explored in adults in young patients. By contrast, the pathogenesis of CNM appears to be distinct. TERT-p mutations may identify the rare subset of spitzoid melanocytic lesions prone to disseminate.","abstract":"Despite remarkable advances in the genomic characterization of adult melanoma, the molecular pathogenesis of pediatric melanoma remains largely unknown. We analyzed 15 conventional melanomas (CM), 3 melanomas arising in congenital nevi (CNM), and 5 spitzoid melanomas (SM), using various platforms, including whole genome or exome sequencing, molecular inversion probe assay, and/or targeted sequencing. CM demonstrated a high burden of somatic single nucleotide variations (SNV), with each case containing a TERT promoter (TERT-p) mutation, 13/15 containing an activating BRAF V600 mutation, and &gt;80% of the identified SNV consistent with UV damage. By contrast, the 3 CNM contained an activating NRAS Q61 mutation and no TERT-p mutations. SM were characterized by chromosomal rearrangements resulting in activated kinase signaling in 40%, and an absence of TERT-p mutations except for the one SM that succumbed to hematogenous metastasis. We conclude that pediatric CM has a very similar UV-induced mutational spectrum to that found in the adult counterpart, emphasizing the need to promote sun protection practices in early life and to improve access to therapeutic agents being explored in adults in young patients. By contrast, the pathogenesis of CNM appears to be distinct. TERT-p mutations may identify the rare subset of spitzoid melanocytic lesions prone to disseminate.","study_type":"Other","pubmed_ids":[25268584],"external_links":null,"is_released":true,"released_date":"2014-07-23T15:55:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000902","title":"Metastatic_Breast_Cancer_Whole_Genome","description":"We propose to definitively characterise the somatic genetics of Metastatic breast cancer through generation of comprehensive catalogues of somatic mutations in Metastatic breast cancer cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.","abstract":"All cancers arise due to somatically acquired mutations in their genomes which alter the function of key cancer genes. Understanding the critical mutational events underlying the development of cancer is paramount for advancing prevention, early detection and effective treatment of the disease. Breast cancer is the most common cause of cancer death among women. Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-23T16:16:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000903","title":"Genome_Diversity_in_Africa_Project","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from Africa have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within Africa would facilitate genomic epidemiological studies in the region.The Genome Diversity in Africa Project (GDAP) will extend and expand the African Genome Variation (AGV) project, an international collaboration aimed to produce a comprehensive catalogue of human genetic variation in Sub-Saharan Africa (SSA). Using a sequencing-based approach, GDA project aims to capture human genetic variation in Africa, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in Africa, as well as providing a global resource to help design, implement and interpret genomic studies in African populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out whole genome sequencing of up to 2000 individuals across Africa (100 individuals from each ethnolinguistic group), and complement these data with 2.5M Illumina genotyping. We have already completed sequencing at low coverage (4x) of 700 individuals across SSA, we are now adding an additional 500 samples from up to 5 ethno-linguistic groups within Africa, including populations from Morocco, Ghana and Kenya.Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from Africa accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across Africa; 3) develop a cost-efficient, next-generation genotype array for diverse populations across Africa; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics.","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in Africa, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in Africa, as well as providing a global resource to help design, implement and interpret genomic studies in African populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out whole genome sequencing of up to 2000 individuals across Africa (100 individuals from each ethnolinguistic group), and complement these data with 2.5M Illumina genotyping. We have already completed sequencing at low coverage (4x) of 700 individuals across SSA, we are now adding an additional 500 samples from up to 5 ethno-linguistic groups within Africa, including populations from Morocco, Ghana and Kenya. Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from Africa accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across Africa; 3) develop a cost-efficient, next-generation genotype array for diverse populations across Africa; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000904","title":"Exome sequencing to identify predisposition to Wilms tumour","description":"To identify new Wilms tumor predisposition genes, we performed whole-exome paired-end sequencing of lymphocyte DNA from 12 affected individuals from six unrelated, non-syndromic Wilms tumor families in which known causes had been excluded.We prepared DNA libraries from 1.5 mg blood-derived genomic DNA using the Paired-End DNA Sample Preparation Kit (Ilumina). DNAwas fragmented using Covaris technology and the libraries were prepared without gel size selection. We performed target enrichment using the TruSeq Exome Enrichment Kit (Illumina) by targeting 62 mb of the human genome. The captured DNA libraries were PCR amplified using the supplied paired-end PCR primers.Sequencing was performed with an Illumina HiSeq2000 generating 2?101 bp reads.","abstract":"To identify new Wilms tumor predisposition genes, we performed whole-exome paired-end sequencing of lymphocyte DNA from 12 affected individuals from six unrelated, non-syndromic Wilms tumor families in which known causes had been excluded.We prepared DNA libraries from 1.5 mg blood-derived genomic DNA using the Paired-End DNA Sample Preparation Kit (Ilumina). DNAwas fragmented using Covaris technology and the libraries were prepared without gel size selection. We performed target enrichment using the TruSeq Exome Enrichment Kit (Illumina) by targeting 62 mb of the human genome. The captured DNA libraries were PCR amplified using the supplied paired-end PCR primers.Sequencing was performed with an Illumina HiSeq2000 generating 2?101 bp reads.","study_type":"Other","pubmed_ids":[25099282],"external_links":null,"is_released":true,"released_date":"2014-07-24T16:21:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000905","title":"Genomic landscape of carcinogen induced mouse skin squamous cell carcinoma","description":"While mouse models are routinely used to decipher the mechanisms regulating tumor initiation and progression, it is still unclear whether tumorigenesis in mice is mediated by the same spectrum of mutations found in human cancer. In this study, we performed the first comprehensive genomic analysis of 9,10-dimethyl-1,2-benzanthracene (DMBA) induced skin squamous cell carcinoma (SCC), the most commonly used cancer model. Using whole exome sequencing, we uncovered a unique mutational signature of DMBA induced SCCs and identified recurrently mutated genes and chromosomal amplifications that are likely to act as drivers of tumorigenesis.","abstract":"While mouse models are routinely used to decipher the mechanisms regulating tumor initiation and progression, it is still unclear whether tumorigenesis in mice is mediated by the same spectrum of mutations found in human cancer. In this study, we performed the first comprehensive genomic analysis of 9,10-dimethyl-1,2-benzanthracene (DMBA) induced skin squamous cell carcinoma (SCC), the most commonly used cancer model. Using whole exome sequencing, we uncovered a unique mutational signature of DMBA induced SCCs and identified recurrently mutated genes and chromosomal amplifications that are likely to act as drivers of tumorigenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000906","title":"Mutations in the SIX1/2 pathway and the DROSHA/DGCR8 miRNA microprocessor complex underlie high-risk blastemal type Wilms tumors","description":"Blastemal histology in chemotherapy-treated pediatric Wilms tumors (nephroblastoma) is associated with adverse prognosis. In order to find novel therapeutic leads for this subgroup of patients, we analyzed 58 such Wilms tumors by exome and transcriptome analysis and validated our findings in larger independent cohorts. Recurrent mutations identified either somatically or in the germline included a hotspot mutation (Q177R) in the homeodomain of SIX1 and SIX2 in tumors with high proliferative potential, mutations in microprocessor genes like DROSHA, DGCR8, DICER1 and DIS3L2, and alterations in IGF2, MYCN, and TP53, the latter being strongly associated with dismal outcome. DROSHA and DGCR8 mutations had a strong effect on miRNA profiles in tumors, which we confirmed in cell lines transfected with mutant DROSHA.","abstract":"Blastemal histology in chemotherapy-treated pediatric Wilms tumors (nephroblastoma) is associated with adverse prognosis. In order to find novel therapeutic leads for this subgroup of patients, we analyzed 58 such Wilms tumors by exome and transcriptome analysis and validated our findings in larger independent cohorts. Recurrent mutations identified either somatically or in the germline included a hotspot mutation (Q177R) in the homeodomain of SIX1 and SIX2 in tumors with high proliferative potential, mutations in microprocessor genes like DROSHA, DGCR8, DICER1 and DIS3L2, and alterations in IGF2, MYCN, and TP53, the latter being strongly associated with dismal outcome. DROSHA and DGCR8 mutations had a strong effect on miRNA profiles in tumors, which we confirmed in cell lines transfected with mutant DROSHA.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-28T14:04:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000907","title":"Von Hippel-Lindau syndrome multi-region exome sequencing project from two patients undertaken at Cancer Research UK's London Research Institute","description":"Multi-region whole exome sequencing of tumours from patients with Von Hippel-Lindau syndrome reveals convergence of mutayional events upon the PI3L-AKT-mTOR signalling pathway.","abstract":"Multi-region whole exome sequencing of tumours from patients with Von Hippel-Lindau syndrome reveals convergence of mutayional events upon the PI3L-AKT-mTOR signalling pathway.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-29T10:59:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000908","title":"Evolution of the African pygmy phenotype","description":"The evolutionary history of the human ‘pygmy’ phenotype (small body size), a characteristic of African and Southeast Asian rainforest hunter-gatherers, is largely unknown. Here we use a genome-wide admixture mapping analysis to identify 16 genomic regions that are significantly associated with the pygmy phenotype in the Batwa, a rainforest hunter-gatherer population from Uganda (East Central Africa). The identified genomic regions have multiple attributes that provide supporting evidence of genuine association with the pygmy phenotype, including enrichments for SNPs previously associated with stature variation in Europeans and for genes with growth hormone receptor and regulation functions. To test adaptive evolutionary hypotheses we computed the haplotype-based iHS statistic and the level of population differentiation (FST) between the Batwa and their agricultural neighbors, the Bakiga, for each SNP. Both |iHS| and FST values were significantly higher for SNPs within the Batwa pygmy phenotype-associated regions than the remainder of the genome, a signature of polygenic adaptation. In contrast, when we expanded our analysis to include Baka rainforest hunter-gatherers from Cameroon and Gabon (West Central Africa) and Nzebi and Nzime neighboring agriculturalists, we did not observe elevated |iHS| or FST values in these genomic regions. Together, these results suggest adaptive and at least partially convergent origins of the pygmy phenotype even within Africa, supporting the hypothesis that small body size confers a selective advantage for tropical rainforest hunter-gatherers but raising questions about the antiquity of this behavior.","abstract":"The evolutionary history of the human ‘pygmy’ phenotype (small body size), a characteristic of African and Southeast Asian rainforest hunter-gatherers, is largely unknown. Here we use a genome-wide admixture mapping analysis to identify 16 genomic regions that are significantly associated with the pygmy phenotype in the Batwa, a rainforest hunter-gatherer population from Uganda (East Central Africa). The identified genomic regions have multiple attributes that provide supporting evidence of genuine association with the pygmy phenotype, including enrichments for SNPs previously associated with stature variation in Europeans and for genes with growth hormone receptor and regulation functions. To test adaptive evolutionary hypotheses we computed the haplotype-based iHS statistic and the level of population differentiation (FST) between the Batwa and their agricultural neighbors, the Bakiga, for each SNP. Both |iHS| and FST values were significantly higher for SNPs within the Batwa pygmy phenotype-associated regions than the remainder of the genome, a signature of polygenic adaptation. In contrast, when we expanded our analysis to include Baka rainforest hunter-gatherers from Cameroon and Gabon (West Central Africa) and Nzebi and Nzime neighboring agriculturalists, we did not observe elevated |iHS| or FST values in these genomic regions. Together, these results suggest adaptive and at least partially convergent origins of the pygmy phenotype even within Africa, supporting the hypothesis that small body size confers a selective advantage for tropical rainforest hunter-gatherers but raising questions about the antiquity of this behavior.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-29T16:46:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000909","title":"Normal brain controls for ICGC PedBrain DNA methylation sequencing","description":"DNA methylation profiling of 8 control samples from adult (4) and fetal  brain (4) used, for example, for the following studies: Mack, Witt, et al. Epigenomic alterations define lethal CIMP-positive  ependymomas of infancy. Nature 506(7489):445-450, 2014 (see EGAS00001000443) Hovestadt, et al. Decoding the regulatory landscape of medulloblastoma  using DNA methylation sequencing. 510(7506):537-541, 2014 (see  EGAS00001000561)","abstract":"DNA methylation profiling of 8 control samples from adult (4) and fetal  brain (4) used, for example, for the following studies: Mack, Witt, et al. Epigenomic alterations define lethal CIMP-positive  ependymomas of infancy. Nature 506(7489):445-450, 2014 (see EGAS00001000443) Hovestadt, et al. Decoding the regulatory landscape of medulloblastoma  using DNA methylation sequencing. 510(7506):537-541, 2014 (see  EGAS00001000561)","study_type":"Other","pubmed_ids":[24553142,24847876],"external_links":null,"is_released":true,"released_date":"2014-07-30T09:54:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000910","title":"DNA methylation repeatability in the Lothian Birth Cohorts of 1921 and 1936.","description":"The repeatability of longitudinal measures of whole blood DNA methylation (obtained using the Illumina 450k chip) was assessed in two cohorts of ageing. The Lothian Birth Cohort of 1921 and the Lothian Birth Cohort of 1936. Data were collected at ages 70, 73, and 76 (LBC1936) and 79, 87, 90 (LBC1921) with 478 participants having two or more measures of methylation.","abstract":"The repeatability of longitudinal measures of whole blood DNA methylation (obtained using the Illumina 450k chip) was assessed in two cohorts of ageing. The Lothian Birth Cohort of 1921 and the Lothian Birth Cohort of 1936. Data were collected at ages 70, 73, and 76 (LBC1936) and 79, 87, 90 (LBC1921) with 478 participants having two or more measures of methylation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-30T10:31:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000911","title":"Pac_Bio_sequencing_of_yeast_strains","description":"Richard Durbin in collaboration with Ville Mustonen, Gianni Liti (Nice), Jared Simpson(Toronto), Jonas Warringer (Gothenburg).In the past we have sequenced a variety of S.cerevisiae and S.paradoxus yeast strains withboth capillary and Illumina sequencing (Nature 2009) and used them for functional variationgenetics (Genome Research 2011, PLoS Genetics 2011, Genetics 2013). However mostchromosomes and in particular sub-telomeric regions are still incompletely assembled. Wecurrently have a paper on the sequence assemblies in revision, for which we want betterlarge scale chromosome structure in the assemblies to address come concerns raised. Wealso would like chromosomal scale assemblies for other ongoing work. Here we propose toapply PacBio long-read sequencing to 10 natural strains of S. cerevisiae and S. paradoxuswith the aim of generating finished and high quality genome assemblies of representativesfrom the main phylogenetic lineages in these two species. These yeast lineages have beenused extensively by us and others and serve as key models for understanding populationgenomics, complex traits, speciation and the evolution of the genotype-phenotyperelationship. As well as supporting out future work the resulting assemblies would be madepublicly available as resources for others.Yeast strains to be sequenced:S. cereviaiseSc. DBVPG6044 West AfricanYPS128 North AmericaDBVPG6765 Wine EuropeanY12 SakeUWOPS03.461.4 MalaysianSK1 LabS. paradoxusYPS138 North AmericanZ1.1 Europe (Silwood Park)N44 Far Eastern RussiaUWOPS91-917.1 Hawaii","abstract":"In the past we have sequenced a variety of S.cerevisiae and S.paradoxus yeast strains withboth capillary and Illumina sequencing (Nature 2009) and used them for functional variationgenetics (Genome Research 2011, PLoS Genetics 2011, Genetics 2013). However mostchromosomes and in particular sub-telomeric regions are still incompletely assembled.Therefore we have applied PacBio long-read sequencing to 10 natural strains of S. cerevisiaeand S. paradoxus.Yeast strains to sequenced:S. cereviaiseSc. DBVPG6044 West AfricanYPS128 North AmericaDBVPG6765 Wine EuropeanY12 SakeUWOPS03.461.4 MalaysianSK1 LabS. paradoxusYPS138 North AmeicanZ1.1 Europe (Silwood Park)N44 Far Eastern RussiaUWOPS91-917.1 Hawaii","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000912","title":"Genome_Diversity_in_Africa_Project","description":"Globally, human populations show structured genetic diversity as a result of geographicaldispersion, selection and drift. Understanding this genetic variation can provide insights intothe evolutionary processes that shape both human adaptation and variation in disease.Populations from SSA have the highest levels of genetic diversity. This characteristic, inaddition to historical genetic admixture, can lead to complexities in the design of studiesassessing the genetic determinants of disease and human variation. However, such studiesof African populations are also likely to provide new opportunities to discover novel diseasesusceptibility loci and variants and refine gene–disease association signals. A systematicassessment of genetic diversity within SSA would facilitate genomic epidemiological studiesin the region.The African Genome Variation Project (AGVP) is an international collaboration that aims toproduce a comprehensive catalogue of human genetic variation in SSA. This resource hasextended our understanding of population history, patterns of genetic diversity within andamong populations in SSA, as well as providing a global resource to help design, implementand interpret genomic studies.The Genome Diversity in Africa Project (GDAP) will extend and expand the African GenomeVariation (AGV) project. Using a sequencing-based approach, GDA project aims to produce acomprehensive catalogue of human genetic variation in SSA, including single nucleotidepolymorphisms (SNPs), structural variants, and haplotypes. This resource will make asubstantial contribution to understanding patterns of genetic diversity within and amongpopulations in SSA, as well as providing a global resource to help design, implement andinterpret genomic studies in SSA populations and studies comprising globally diversepopulations, complementing existing genomic resources. Specifically, we plan to carry out lowcoverage (4x) whole genome sequencing of up to 2000 individuals across Africa (100individuals from each ethnolinguistic group), and complement these data with 2.5M Illuminagenotyping. We have already completed sequencing of 700 individuals across SSA. With thisapplication, we apply for funding to sequence and genotype an additional 400 individualsfrom 4 ethno-linguistic groups within Africa, including populations from Ethiopia, Morocco,Ghana and Seychelles.Our scientific objectives are to: 1) develop a resource that provides a comprehensivecatalogue of genetic variation in populations from SSA accessible to the global scientificcommunity; 2) characterise population genetic diversity, structure, gene flow and admixtureacross SSA; 3) develop a cost-efficient, next-generation genotype array for diversepopulations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource forenhancing fine-mapping disease susceptibility loci. These scientific objectives will besupported by cross-cutting operational activities, including network and management of theconsortium, research ethics, and research capacity building in statistical genetics andbioinformatics.","abstract":"Globally, human populations show structured genetic diversity as a result of geographicaldispersion, selection and drift. Understanding this genetic variation can provide insights intoour human origins and the evolutionary processes that shape both human adaptation andvariation in disease. Populations from SSA have the highest levels of genetic diversity. Thischaracteristic, in addition to historical genetic admixture, can lead to complexities in thedesign of studies assessing the genetic determinants of disease and human variation.However, such studies of African populations are also likely to provide new opportunities todiscover novel disease susceptibility loci and variants and refine gene–disease associationsignals. A systematic assessment of genetic diversity within SSA would facilitate genomicepidemiological studies in the region.The African Genome Variation Project (AGVP) is an international collaboration that aims toproduce a comprehensive catalogue of human genetic variation in SSA. This resource hasextended our understanding of our human origins, population history, patterns of geneticdiversity within and among populations in SSA, as well as providing a global resource to helpdesign, implement and interpret genomic studies.The Genome Diversity in Africa Project (GDAP) will extend and expand the African GenomeVariation (AGV) project. Using a sequencing-based approach, GDA project aims to produce acomprehensive catalogue of human genetic variation in SSA, including single nucleotidepolymorphisms (SNPs), structural variants, and haplotypes. This resource will make asubstantial contribution to understanding patterns of genetic diversity within and amongpopulations in SSA, as well as providing a global resource to help design, implement andinterpret genomic studies in SSA populations and studies comprising globally diversepopulations, complementing existing genomic resources. Specifically, we plan to carry out lowcoverage (4x) whole genome sequencing of up to 2000 individuals across Africa (100individuals from each ethnolinguistic group), and complement these data with 2.5M Illuminagenotyping.Our scientific objectives are to: 1) develop a resource that provides a comprehensivecatalogue of genetic variation in populations from SSA accessible to the global scientificcommunity; 2) characterise population genetic diversity, structure, gene flow and admixtureacross SSA; 3) develop a cost-efficient, next-generation genotype array for diversepopulations across SSA; and 4) facilitate whole genome-sequencing association studies ofcomplex traits and diseases by developing a reference panel for imputation and resource forenhancing fine-mapping disease susceptibility loci. These scientific objectives will besupported by cross-cutting operational activities, including network and management of theconsortium, research ethics, and research capacity building in statistical genetics andbioinformatics","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000913","title":"WTCCC3_Anorexia_Nervosa","description":"As part of the Genetic Consortium for Anorexia Nervosa (GCAN) and Wellcome Trust CaseControl Consortium 3 (WTCCC3), we have amassed the largest anorexia nervosa (AN)sample in the world (~4,000). Following the WTCCC3 GWAS, we secured funding from theKlarman Family Foundation to extend the genetic analyses to variants on the exome chip(CoreExome array). This pre-lim relates to carrying out genotyping on the CoreExome arrayon up to a maximum of 580 new samples.","abstract":"As part of the Genetic Consortium for Anorexia Nervosa (GCAN) and Wellcome Trust Case Control Consortium 3 (WTCCC3), we have amassed the largest anorexia nervosa (AN) sample in the world. We propose a well-powered evaluation of the hypothesis that uncommon coding variation plays a role in AN. We propose to evaluate the role of uncommon exon variation in AN in 3,000 female cases and 3,000 archived matched controls in a cost-effective manner by using the Illumina HumanExome chip, which captures missense and nonsense coding variation with MAF ?0.005, and a substantial fraction with MAF 0.0005-0.005. This chip contains ~230K missense and nonsense coding variants identified via exome sequencing of 12,028 European individuals. The chip contains SNPs from the Psychiatric GWAS Consortium mega-analyses for autism, major depression, schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. We will genotype AN cases and controls using the Illumina HumanExome chip and conduct rigorous QC. We will evaluate the role of uncommon coding variants in AN conducting single SNP tests along with tests that aggregate variation within exons and genes, and will incorporate appropriately selected covariates and control for potential biases (e.g., population stratification). We will aim to identify biological pathways for AN with high confidence by rigorous assessment of the extent to which genomic results are enriched for smaller p-values in genes from both classical and novel empirical pathways. Finally, we will compare our results with exome chip genotyping conducted for other psychiatric disorders (autism spectrum disorders, bipolar disorder, schizophrenia, and attention deficit hyperactivity disorder) in order to look for shared genetic risk factors. The proposed study will provide a rigorous and well-powered evaluation of the role of uncommon exon variation in AN. If variants are identified, these discoveries could provide rapid and actionable insights into the genetic causes of AN.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-31T14:25:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000914","title":"Assessing_rare_exonic_variation_in_osteoarthritis","description":"Following the arcOGEN GWAS for osteoarthritis, we are now focusing on exonic variationand are requesting funding to genotype ~2,400 of the arcOGEN samples (which do not haveGWAS data) on the CoreExome array","abstract":"Following the arcOGEN GWAS for osteoarthritis, we are now focusing on exonic variationand are requesting funding to genotype ~2,400 of the arcOGEN samples (which do not haveGWAS data) on the CoreExome array","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000915","title":"Malaria_CP3_reference_set_gneotyping","description":"We have sequenced whole genomes of 400 individuals from multiple ethnic groups in BurkinaFaso, Cameroon and Tanzania to support our multi-centre GWAS of severe malaria. Thesame set of individuals has been genotyped on Illumina 2.5M-8 chip to confirm sampleidentities and to assess genotype concordance.The primary motive of this study is to maximise GWAS power but these data will provide aunique repository of information about genome variation and GWAS assay design in a subsetof African populations.The data is available to the scientific community through an Independent Data AccessCommittee. Please see http://www.malariagen.net/node/284 for application process details.","abstract":"We have sequenced whole genomes of 400 individuals from multiple ethnic groups in BurkinaFaso, Cameroon and Tanzania to support our multi-centre GWAS of severe malaria. Thesame set of individuals has been genotyped on Illumina 2.5M-8 chip to confirm sampleidentities and to assess genotype concordance.The primary motive of this study is to maximise GWAS power but these data will provide aunique repository of information about genome variation and GWAS assay design in a subsetof African populations.The data is available to the scientific community through an Independent Data AccessCommittee. Please see http://www.malariagen.net/node/284 for application process details.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000916","title":"Developmental_Dysplasia_of_the_Hip__DDH_","description":"The National Joint Registry for England and Wales (NJR) has become established as one of the largest repositories of clinical information about patients undergoing hip and knee replacement. The primary aim of this proposal is to examine the feasibility of adding value to that clinical information by partnering it with a DNA dataset to allow its use to be extended to the study of the underlying pathogenesis of diseases of the hip and knee, and the complications of their treatment. We will do this 1) by establishing a mechanism for accessing and linking pseudo-anonymised demographic and phenotype data between the NJR database and the proposed DNA Biobank; 2) by validating the collection of postal DNA samples from consenting NJR patients; and 3) by genotyping genome-wide 900 patients with the condition developmental dysplasia of the hip (DDH) to find variants that play a role in this heritable condition. The successful demonstration that the NJR can be used to establish a DNA Biobank will provide a powerful platform to examine the genetic basis for a wide range of joint diseases, and the complications of their treatment. This proposal is to carry out the genotyping portion of this project on the current CoreExome array","abstract":"The National Joint Registry for England and Wales (NJR) has become established as one of the largest repositories of clinical information about patients undergoing hip and knee replacement. The primary aim of this proposal is to examine the feasibility of adding value to that clinical information by partnering it with a DNA dataset to allow its use to be extended to the study of the underlying pathogenesis of diseases of the hip and knee, and the complications of their treatment. We will do this 1) by establishing a mechanism for accessing and linking pseudo-anonymised demographic and phenotype data between the NJR database and the proposed DNA Biobank; 2) by validating the collection of postal DNA samples from consenting NJR patients; and 3) by genotyping genome-wide 900 patients with the condition developmental dysplasia of the hip (DDH) to find variants that play a role in this heritable condition. The successful demonstration that the NJR can be used to establish a DNA Biobank will provide a powerful platform to examine the genetic basis for a wide range of joint diseases, and the complications of their treatment. This proposal is to carry out the genotyping portion of this project on the current CoreExome array","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-31T14:27:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000917","title":"ARGO_GWAS","description":"Osteoarthritis (OA) is the most common form of arthritis affecting ~40% of people over the age of 70. OA is characterised by cartilage degeneration in the synovial joints and presents one of the leading causes of chronic disability and impaired quality of life in the developed world.The ARGO study is an ongoing collection of well-phenotyped OA patients undergoing total joint replacement and is based in Greece.","abstract":"Osteoarthritis (OA) is the most common form of arthritis affecting ~40% of people over the age of 70. OA is characterised by cartilage degeneration in the synovial joints and presents one of the leading causes of chronic disability and impaired quality of life in the developed world.The ARGO study is an ongoing collection of well-phenotyped OA patients undergoing total joint replacement and is based in Greece.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-31T14:28:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000918","title":"Genome_wide_association_study_of_vaccine_responses_in_infants_living_in_the_Developing_World__VaccGene___Phase_II_African_Cohorts","description":"Human genetic heterogeneity accounts for approximately 70% of the observed variability inresponse to common childhood vaccinations. Identifying the elements of this heterogeneitywill enable the development of vaccines which have improved clinical and cost effectivenessthrough rational adjuventation approaches, or by targeting particular at-risk or responsivesubgroups. The studies published to date have been limited in terms of the number of vaccinesubtypes analysed, diversity of the populations included, sample sizes and breadth of otherenvironmental and lifestyle variables which may explain some of the remainder of variation inthe response to each vaccine. Nevertheless, these studies have proposed that the geneswhich harbour the variants associated with vaccine responsiveness reside within regions ofthe genome associated with immune function such as the HLA locus and FOXP1and ITGAL.We are proposing one of the largest genome-wide association studies of vaccine responseever undertaken, which will provide unparalleled power to identify the genetic factorsassociated with the response to all of the most commonly used childhood vaccinesworldwide. For the first phase of the project (Prelim I0308) we genotyped ca. 1,400 childrenfrom the Entebbe Mother and Baby (EMaB) study, an ongoing birth cohort in southernUganda, using the Illumina HumanOmni2.5-8 chip. Analyses for response to vaccinationagainst diphtheria, tetanus, pertussis, Haemophilus influenzae, measles, hepatitis B and BCGare now underway. Working alongside other ongoing studies, we plan for the second phaseof the project to expand sample sizes to up to 7,000 individuals in total. This large cohort willinclude 1,500 South African infants, 500 Burkina Faso infants, 1,800 children from Ecuadorand up to 1,800 from a variety of countries (MAL-ED Consortium). The principal measuredphenotypes will be the serological responses at 6 or 12 months of age to the vaccinesadministered to all enrolled children as part of expanded programme of immunisation in allcountries. As for the primary Ugandan study the responses will be analysed as quantitativetraits using mixed model (GEMMA) analyses following imputation using a combined 1000Genome and African Genome Variation Project reference panel. The data will be analysed asone large discovery mega-analysis to maximise the power of finding the relevant associatedvariants. Interim GWAS analyses will be performed on each population to test for populationspecific signals. Other phenotypes that will be assessed in the new studies includequantitative response to BCG, rotavirus and pneumococcal vaccines (South Africa, Ecuadorand Uganda), clinical and immunological response to malaria vaccines (Burkina),immunological correlates of atopy (Ecuador and Uganda) and malaria infection (Burkina,Ecuador and Uganda) in addition to non-communicable disease traits such as blood pressurepage 1[A8] If applicable, provide text (abstract) which will accompany data for this study in the ENA/EGA.[A9] Does this project use samples?[A10] Please choose which types of sample you will be using[A12] Please state the anticipated date (month/year) samples will be available in-house (if known). If samples arealready in-house, type 'in-house' here. Please note that for sequencing, genotyping and microarrays this is essentialfor scheduling the work.[A13] Please state the anticipated project start date (month/year).[A14] Please state the project duration (months).[A15] Please read WTSI's Data Sharing Policy and Guidelines, then explain your data sharing plans for the project[A16] Are the data sharing plans of this project compliant with the Institute's Guidelines?[A17] Are there any conflicts of interest related to this proposal?(Uganda).We are requesting funds to genotype on the Illumina HumanOmni2.5-8 platform 2,000 Africaninfants recruited through ongoing maternal and child vaccine clinical trials (againstpneumococcus in Soweto, South Africa, and malaria in Banfora, Burkina Faso). The DNAfrom the Burkina cohort is at the University of Oxford and ready to be shipped, while the DNAfrom the South African cohort will be available by mid-2014. Appropriate consent for geneticanalyses has been acquired for the proposed study cohorts from both local ethics committeesand UK-based Committees.","abstract":"These data have been generated in the context of one of the largest genome-wideassociation studies of vaccine responses ever undertaken, which will provide unparalleledpower to identify the genetic factors associated with the response to all of the most commonlyused childhood vaccines worldwide. The large cohort of ca. 7,000 individuals includes 1,400children from Uganda, 1,500 South African infants, 500 Burkina Faso infants, 1,800 childrenfrom Ecuador and up to 1,800 from a variety of countries (MAL-ED Consortium) recruitedthrough existing birth cohorts (Uganda, Ecuador and MAL-ED countries) or ongoing maternaland child vaccine clinical trials (against pneumococcus in South Africa and malaria inBurkina). The principal analysed phenotypes are the serological responses at 6 or 12 monthsof age to the vaccines administered to all enrolled children as part of expanded programme ofimmunisation in all countries (including diphtheria, tetanus, pertussis, Haemophilusinfluenzae, measles and hepatitis B). Other phenotypes that are being assessed in the newstudies include quantitative response to BCG, rotavirus and pneumococcal vaccines (SouthAfrica, Ecuador and Uganda), clinical and immunological response to malaria vaccines(Burkina), immunological correlates of atopy (Ecuador and Uganda) and malaria infection(Burkina, Ecuador and Uganda) in addition to non-communicable disease traits such as bloodpressure (Uganda)","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-31T14:28:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000919","title":"CoreExome_Array_Genotyping_in_an_Amish_population","description":"Last year we reported HELIC validation of the APOC3 R19X lipid traits association, previouslyidentified in the Amish. The variant has drifted up in frequency from 0.05% to 2-3%independently in the Cretan isolate and the Amish and demonstrates the same highly-significant cardioprotective effect (reduced TG, increased HDL levels). We are embarking ona meta-analysis across the HELIC-MANOLIS and existing Amish exome chip data (~1200 ineach cohort). Here we request CoreExome genotyping of an additional set of 2800 Amishsamples with relevant trait data to boost power in the meta-analysis. This experiment will alsohelp build a strong relationship between the two cohorts ahead of the high-depth WGS isolateexperiment","abstract":"Last year we reported HELIC validation of the APOC3 R19X lipid traits association, previouslyidentified in the Amish. The variant has drifted up in frequency from 0.05% to 2-3%independently in the Cretan isolate and the Amish and demonstrates the same highly-significant cardioprotective effect (reduced TG, increased HDL levels). We are embarking ona meta-analysis across the HELIC-MANOLIS and existing Amish exome chip data (~1200 ineach cohort). Here we request CoreExome genotyping of an additional set of 2800 Amishsamples with relevant trait data to boost power in the meta-analysis. This experiment will alsohelp build a strong relationship between the two cohorts ahead of the high-depth WGS isolateexperiment","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000920","title":"Replication_and_fine_mapping_of_genome_wide_associated_loci_for_podoconiosis__omni2_5_8_gwalpc__gwalpc_","description":"Podoconiosis (endemic, non-filarial elephantiasis) is a tropical lymphoedema resulting fromlong-term barefoot exposure to red clay soil derived from volcanic rock. WHO has recentlyrecognized it as a Neglected Tropical Disease (NTD) which causes overwhelming economicand social burdens in impoverished communities. Only a subset of exposed individualsdevelops podoconiosis. Consistent with a genetic aetiology, our previous studies indicatedhigh heritability (~63%). A genome-wide association study (GWAS) with 194 cases and 203controls from southern Ethiopia found genome-wide significant association of podoconiosiswith rs17612858, located 5.7kb from HLA-DQA1 and suggestive associations with furtherSNPs across the genome.Proposed workWe have been awarded funding from the MRC to:i) extend the podoconiosis bioresource to include a further 600 samples from the GWASpopulation in southern Ethiopia, 1600 samples from 2 ethnically distinct Ethiopian populationsin Ethiopia and 800 samples from Cameroonii) confirm associations identified in the initial GWAS by typing associated SNPs in each ofthese populations;iii) perform high resolution HLA Class II typing of cases, family members and controls;iv) GWAS 1700 samples, 2000 samples will be available, 1000 cases, 1000 controlsv) fine map the region using these population-specific variants to identify putative causalvariants.We plan to carry out the experiments for ii. (covered in original pre-lim) and iv. at the Sanger","abstract":"Podoconiosis (endemic, non-filarial elephantiasis) is a tropical lymphoedema resulting fromlong-term barefoot exposure to red clay soil derived from volcanic rock. WHO has recentlyrecognized it as a Neglected Tropical Disease (NTD) which causes overwhelming economicand social burdens in impoverished communities. Only a subset of exposed individualsdevelops podoconiosis. Consistent with a genetic aetiology, our previous studies indicatedhigh heritability (~63%). A genome-wide association study (GWAS) with 194 cases and 203controls from southern Ethiopia found genome-wide significant association of podoconiosiswith rs17612858, located 5.7kb from HLA-DQA1 and suggestive associations with furtherSNPs across the genome.Proposed workWe have been awarded funding from the MRC to:i) extend the podoconiosis bioresource to include a further 600 samples from the GWASpopulation in southern Ethiopia, 1600 samples from 2 ethnically distinct Ethiopian populationsin Ethiopia and 800 samples from Cameroonii) confirm associations identified in the initial GWAS by typing associated SNPs in each ofthese populations;iii) perform high resolution HLA Class II typing of cases, family members and controls;iv) GWAS 1700 samples, 2000 samples will be available, 1000 cases, 1000 controlsv) fine map the region using these population-specific variants to identify putative causalvariants.We plan to carry out the experiments for ii. (covered in original pre-lim) and iv. at the Sanger","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000921","title":"Replication_and_fine_mapping_of_genome_wide_associated_loci_for_podoconiosis","description":"Podoconiosis is a non-infectious geochemical disease that results in swelling of the lowerlegs. Podoconiosis is an important yet neglected public health problem particularly in tropicalAfrican countries. Previous work has estimated the sibling recurrence risk ratio and heritabilityfor podoconiosis to be 5.07 and 62.9% respectively. A GWAS conducted in 194 patients and203 controls found significant association between podoconiosis and SNPs in class II of theMHC. In addition, suggestive associations between podoconiosis and non-HLA loci wereidentified, including SNPs on chromosomes 8, 13 and 17.We have obtained MRC funding to genotype ~2000 samples on the HumanOmni2.5-8 array.The total available sample set is 3200 samples so we are applying to do the remaining 1200samples.We aim to use 400 cases and 400 controls from 4 ethnically distinct cohorts, Wollaita, north-western Cameroon, western and north-western Ethiopia.As part of the 1200 we currently we have 200 cases and 200 controls on site for Wollaita, weexpect 100 Cameroon samples in the next 5 weeks and the remaining 700 within 12 weeks","abstract":"Podoconiosis is a non-infectious geochemical disease that results in swelling of the lowerlegs. Podoconiosis is an important yet neglected public health problem particularly in tropicalAfrican countries. Previous work has estimated the sibling recurrence risk ratio and heritabilityfor podoconiosis to be 5.07 and 62.9% respectively. A GWAS conducted in 194 patients and203 controls found significant association between podoconiosis and SNPs in class II of theMHC. In addition, suggestive associations between podoconiosis and non-HLA loci wereidentified, including SNPs on chromosomes 8, 13 and 17.We have obtained MRC funding to genotype ~2000 samples on the HumanOmni2.5-8 array.We aim to use 400 cases and 400 controls from 4 ethnically distinct cohorts, Wollaita, north-western Cameroon, western and north-western Ethiopia.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000922","title":"SCOOP_Human_Core_Exome_Genotyping","description":"Obesity is a major public health problem with substantial impacts on morbidity and mortality.Genome-wide association studies (GWAS) for obesity-related traits have proven to be anextremely valuable tool leading to the discovery of over 50 loci to date (PMID:17434869,17496892,18454148, 18604207, 19151714, 20421936, 21708048, 20935630,21935397, 22484627). However, the variants identified explain only a small fraction of thevariance in BMI (body mass index).The SCOOP cohort (PMID: 23563609) is a UK Caucasian subset of the Genetics of ObesityStudy (GOOS) (PMID: 19966786], comprising of individuals with severe early-onset obesity(BMI standard deviation score (SDS) &gt; 3; onset of obesity before the age of 10 years). Werecently carried out an association analysis in 1,509 SCOOP cases and 5,380 populationcontrols, and successfully identified 4 new loci associated with severe obesity (LEPR,PRKCH, PACS1 and RMST) (PMID: 23563609).It is well established that large sample sizes are required to detect common variants withmodest effects. Rare variants may also explain a proportion of the missing heritability andmay be more readily identified at the extremes of a phenotypic distribution. We thereforepropose to build on the success of the previous GWAS, by genotyping and additional 3,500samples from the SCOOP cohort on the Illumina HumanCoreExome beadchip. This chip is ahigh-density array with increased coverage of exonic regions, enabling us to cost-effectivelysearch for both common &amp; rare variants contributing to severe obesity.","abstract":"Obesity is a major public health problem with substantial impacts on morbidity and mortality.Genome-wide association studies (GWAS) for obesity-related traits have proven to be anextremely valuable tool leading to the discovery of over 50 loci to date (PMID:17434869,17496892,18454148, 18604207, 19151714, 20421936, 21708048, 20935630,21935397, 22484627). However, the variants identified explain only a small fraction of thevariance in BMI (body mass index).The SCOOP cohort (PMID: 23563609) is a UK Caucasian subset of the Genetics of ObesityStudy (GOOS) (PMID: 19966786], comprising of individuals with severe early-onset obesity(BMI standard deviation score (SDS) &gt; 3; onset of obesity before the age of 10 years). Werecently carried out an association analysis in 1,509 SCOOP cases and 5,380 populationcontrols, and successfully identified 4 new loci associated with severe obesity (LEPR,PRKCH, PACS1 and RMST) (PMID: 23563609).It is well established that large sample sizes are required to detect common variants withmodest effects. Rare variants may also explain a proportion of the missing heritability andmay be more readily identified at the extremes of a phenotypic distribution. We thereforepropose to build on the success of the previous GWAS, by genotyping and additional 3,500samples from the SCOOP cohort on the Illumina HumanCoreExome beadchip. This chip is ahigh-density array with increased coverage of exonic regions, enabling us to cost-effectivelysearch for both common &amp; rare variants contributing to severe obesity.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000923","title":"Genetic_and_Physiological_basis_of_Thinness__STILTS_","description":"To date virtually all research based at finding genes related to obesity has focused on theupper end of the body mass index (BMI) distribution. As part of this proposal we propose acomplementary gene finding strategy that focuses on the lowest end of the BMI distribution inorder to find genes that confer resistance to obesity in an obesogenic society. Thinnessappears to be a trait that is as stable and heritable as obesity; in studies of European,American and East Indian sibling pairs the heritability for thinness, defined as a weight belowthe 10th percentile, is comparable if not greater than that for increased body weight. Animalstudies have increasingly supported the existence of a particular genetic predisposition tothinness or leanness. For example, the pure-line “I” strain of inbred mice is unusually resistantto the development of dietary obesity. Other animals can be selectively bred for bothleanness and thinness. There appear to be recessive genes for extreme thinness or leannessincluding the halothene gene in pigs, the double-muscling gene in cattle and others. Similarly,Levin and colleagues have studied rats for their resistance to the development of obesity on ahigh fat diet and characterised distinctive phenotypes in diet induced and diet resistantanimals. To date no genetic studies have been conducted in thin humans. The identificationof such genes may provide explain why some individuals do not become obese despiteenvironmental provocation. Insight into the biology of thinness and obesity resistance couldlead to rational preventative strategies for obesity.A STudy Into Lean and Thin Subjects (STILTS) was established in 2005 by Professor ISFarooqi (ISF) at the University of Cambridge Metabolic Research Laboratories (IMS MRL).ISF has been awarded funds from the European Research Council (ERC) and 1,600 peoplewith thinness (defined as a body mass index &lt;18kg/m2) in the absence of chronic disease oreating disorders have been recruited through primary care with the involvement of UKPrimary Care Research Networks (PCRNs). Most of these have a strong family history ofthinness. DNA samples and detailed clinical information will be obtained. In collaboration withDr Ines Barroso, WTSI, we propose to undertake a genome wide association study using theIllumina HumanCoreExome beadchip, a high-density array with increased coverage of exonicregions. Data will be compared to &gt;5,000 UK Caucasian subjects with severe early onsetobesity (SCOOP) and &gt; 10,000 UK controls recruited as part of the Understanding Societystudy. A direct comparison of subjects from STILTS versus SCOOP will provide a verypowerful way of looking for common variants associated with both extremes of the body massindex range. We propose to replicate association signals identified in the STILTS genomewide association study by collaborating with colleagues around the world who have existingGWAS data sets of population based subjects and by using the lowest decile for BMI todefine cases","abstract":"To date virtually all research based at finding genes related to obesity has focused on theupper end of the body mass index (BMI) distribution. As part of this proposal we propose acomplementary gene finding strategy that focuses on the lowest end of the BMI distribution inorder to find genes that confer resistance to obesity in an obesogenic society. Thinnessappears to be a trait that is as stable and heritable as obesity; in studies of European,American and East Indian sibling pairs the heritability for thinness, defined as a weight belowthe 10th percentile, is comparable if not greater than that for increased body weight. Animalstudies have increasingly supported the existence of a particular genetic predisposition tothinness or leanness. For example, the pure-line “I” strain of inbred mice is unusually resistantto the development of dietary obesity. Other animals can be selectively bred for bothleanness and thinness. There appear to be recessive genes for extreme thinness or leannessincluding the halothene gene in pigs, the double-muscling gene in cattle and others. Similarly,Levin and colleagues have studied rats for their resistance to the development of obesity on ahigh fat diet and characterised distinctive phenotypes in diet induced and diet resistantanimals. To date no genetic studies have been conducted in thin humans. The identificationof such genes may provide explain why some individuals do not become obese despiteenvironmental provocation. Insight into the biology of thinness and obesity resistance couldlead to rational preventative strategies for obesity.A STudy Into Lean and Thin Subjects (STILTS) was established in 2005 by Professor ISFarooqi (ISF) at the University of Cambridge Metabolic Research Laboratories (IMS MRL).ISF has been awarded funds from the European Research Council (ERC) and 1,600 peoplewith thinness (defined as a body mass index &lt;18kg/m2) in the absence of chronic disease oreating disorders have been recruited through primary care with the involvement of UKPrimary Care Research Networks (PCRNs). Most of these have a strong family history ofthinness. DNA samples and detailed clinical information will be obtained. In collaboration withDr Ines Barroso, WTSI, we propose to undertake a genome wide association study using theIllumina HumanCoreExome beadchip, a high-density array with increased coverage of exonicregions. Data will be compared to &gt;5,000 UK Caucasian subjects with severe early onsetobesity (SCOOP) and &gt; 10,000 UK controls recruited as part of the Understanding Societystudy. A direct comparison of subjects from STILTS versus SCOOP will provide a verypowerful way of looking for common variants associated with both extremes of the body massindex range. We propose to replicate association signals identified in the STILTS genomewide association study by collaborating with colleagues around the world who have existingGWAS data sets of population based subjects and by using the lowest decile for BMI todefine cases","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000924","title":"Genotyping_of_additional_Inflammatory_Bowel_Disease_cases___2014","description":"Both internal and external funding has enabled 5000 inflammatory bowel disease cases to be\nwhole genome sequenced (CD @4X, UC @2X). The Anderson and Barrett groups are\ncurrently generating genotypes across these samples for comparison to 4000 population\ncontrols sequenced as part of UK10K. The UK10K project has shown that imputing\nsequenced genetic variation into previously GWASed samples greatly increases power to\ndetect association. Given that our study has been designed to detect association to low\nfrequency variation (0.5% and above) these gains in power are especially important. Overall,\nthe UKIBDGC has GWAS data for around 1800 CD samples (Affy 500K) and 3000 UC\nsamples (Affy6), though some of these samples have also been whole genome sequenced.\nHere, we apply to get all remaining non-GWAS and non-WGS IBD cases in the UKIBDGC\n(N=X) genotyped genotyped on the Illumina Core Exome Array","abstract":"Both internal and external funding has enabled 5000 inflammatory bowel disease cases to be\nwhole genome sequenced (CD @4X, UC @2X). The Anderson and Barrett groups are\ncurrently generating genotypes across these samples for comparison to 4000 population\ncontrols sequenced as part of UK10K. The UK10K project has shown that imputing\nsequenced genetic variation into previously GWASed samples greatly increases power to\ndetect association. Given that our study has been designed to detect association to low\nfrequency variation (0.5% and above) these gains in power are especially important. Overall,\nthe UKIBDGC has GWAS data for around 1800 CD samples (Affy 500K) and 3000 UC\nsamples (Affy6), though some of these samples have also been whole genome sequenced.\nHere, we apply to get all remaining non-GWAS and non-WGS IBD cases in the UKIBDGC\n(N=X) genotyped genotyped on the Illumina Core Exome Array","study_type":"Other","pubmed_ids":[28067910],"external_links":null,"is_released":true,"released_date":"2014-07-31T14:32:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000925","title":"Comprehensive genomic profiles of small cell lung cancer","description":"We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. We found bi-allelic inactivation of TP53 and RB1 in nearly all the tumors analyzed, sometimes by complex genomic rearrangements. Two tumors with wild-type RB1 had evidence of chromothripsis leading to overexpression of Cyclin D1, revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumor suppressors TP53 and RB1 is obligatory in SCLC. We further discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Δex2/3. In few cases, SCLC tumors exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signaling in a pre-clinical SCLC mouse model dramatically reduced the number of tumors and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.","abstract":"We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. We found bi-allelic inactivation of TP53 and RB1 in nearly all the tumors analyzed, sometimes by complex genomic rearrangements. Two tumors with wild-type RB1 had evidence of chromothripsis leading to overexpression of Cyclin D1, revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumor suppressors TP53 and RB1 is obligatory in SCLC. We further discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Δex2/3. In few cases, SCLC tumors exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signaling in a pre-clinical SCLC mouse model dramatically reduced the number of tumors and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-07-31T15:47:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000926","title":"Study of non-clear cell renal cell carcinoma","description":"Study of non-clear cell renal cell carcinoma","abstract":"Study of non-clear cell renal cell carcinoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-08-01T17:11:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000927","title":"A Comparative Analysis of Algorithms for Somatic SNV Detection in Cancer","description":"Four recently published algorithms for the detection of somatic SNV sites in matched cancer-normal sequencing datasets are VarScan, SomaticSniper, JointSNVMix and Strelka. In this analysis, we apply these four SNV calling algorithms to cancer- normal Illumina exome sequencing of a chronic myeloid leukaemia (CML) patient. The candidate SNV sites returned by each algorithm are filtered to remove likely false positives, then characterised and compared to investigate the strengths and weaknesses of each SNV calling algorithm.","abstract":"Four recently published algorithms for the detection of somatic SNV sites in matched cancer-normal sequencing datasets are VarScan, SomaticSniper, JointSNVMix and Strelka. In this analysis, we apply these four SNV calling algorithms to cancer- normal Illumina exome sequencing of a chronic myeloid leukaemia (CML) patient. The candidate SNV sites returned by each algorithm are filtered to remove likely false positives, then characterised and compared to investigate the strengths and weaknesses of each SNV calling algorithm.","study_type":"Other","pubmed_ids":[23842810],"external_links":null,"is_released":true,"released_date":"2014-08-04T06:41:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000928","title":"Understanding the genetic determinants of disease using the lens of the splicing code","description":"A fundamental challenge in genomics research is to accurately predict the consequences of genetic variation on gene regulation. We present a new approach that uses a regulatory model of splicing to determine how a variant impacts exon inclusion. This contrasts sharply with, but can be used to amplify the sensitivity of, techniques that compare variants using multiple genomes or genome annotations. By computing ‘misregulation scores’ for 658,420 single nucleotide variations, we observe that our system reliably detects disease-causing variants, even when they are synonymous or located within introns. The analysis reveals genome-wide trends in how mutations cause disease; for example, missense exonic mutations that least impact protein function are five times more likely to disrupt splicing regulation than highly deleterious mutations. Our approach provides new insights into altered regulatory mechanisms in spinal muscular atrophy, nonpolyposis colorectal cancer and autism, and elucidates new candidate disease genes. The regulatory model thus opens the door to previously impossible explorations into how genetic variation impacts human disease.","abstract":"A fundamental challenge in genomics research is to accurately predict the consequences of genetic variation on gene regulation. We present a new approach that uses a regulatory model of splicing to determine how a variant impacts exon inclusion. This contrasts sharply with, but can be used to amplify the sensitivity of, techniques that compare variants using multiple genomes or genome annotations. By computing ‘misregulation scores’ for 658,420 single nucleotide variations, we observe that our system reliably detects disease-causing variants, even when they are synonymous or located within introns. The analysis reveals genome-wide trends in how mutations cause disease; for example, missense exonic mutations that least impact protein function are five times more likely to disrupt splicing regulation than highly deleterious mutations. Our approach provides new insights into altered regulatory mechanisms in spinal muscular atrophy, nonpolyposis colorectal cancer and autism, and elucidates new candidate disease genes. The regulatory model thus opens the door to previously impossible explorations into how genetic variation impacts human disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000929","title":"APCDR GDAP: Genome Diversity in Africa Study (set of 9 samples at high depth)","description":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000930","title":"Intra-tumor heterogeneity of localized lung adenocarcinomas defined by multi-region sequencing","description":"Background: Intra-tumor heterogeneity (ITH) may have profound impacts on biopsy strategy, characterization of actionable targets, treatment planning, and drug resistance. ITH of lung cancers has not been well studied.   Methods: We performed multi-region whole exome sequencing (average sequencing depth 277x) on 48 tumor regions from 11 resected lung adenocarcinomas (8 stage I, 2 stage II and one stage III tumors) followed by deep sequencing validation (average sequencing depth 863x).   Results: All tumors showed clear evidence of spatial ITH. On average, 76% of all mutations and 20/21 known cancer gene mutations were present in all regions of individual tumors (trunk mutations). Copy number analysis did not show substantial difference in large-scale chromosome aberrations. A canonical KRAS p.G12C mutation was detected in only 1 of 4 tumor regions (branch mutations) at exome depth but detected in all four tumor regions (trunk mutations) at increased sequencing depth. In addition, many heterogeneous branch mutations defined by exome sequencing were detectable in all regions of individual tumors with increasing sequencing depth. Significant differences in mutational spectrum were observed in 6 tumors indicating that specific mutational processes were likely operative at different times during development of these tumors. With a median follow up of 21 months post surgery, 3 patients have relapsed and all 3 patients presented with significantly larger fractions of subclonal mutations in their primary tumors.   Conclusions: Although multi-region sampling is still required to fully assess ITH complexity, single biopsy analysis at appropriate depth might be sufficient to identify the majority of known cancer gene mutations in localized lung adenocarcinomas. Larger subclonal mutation fractions may be associated with increased likelihood of postsurgical relapse in patients with localized lung adenocarcinomas. Studies on larger cohort, ideally with comprehensive clinical annotation and repeat biopsy at relapse are needed to fully understand the clinical impact of ITH.","abstract":"Background: Intra-tumor heterogeneity (ITH) may have profound impacts on biopsy strategy, characterization of actionable targets, treatment planning, and drug resistance. ITH of lung cancers has not been well studied.   Methods: We performed multi-region whole exome sequencing (average sequencing depth 277x) on 48 tumor regions from 11 resected lung adenocarcinomas (8 stage I, 2 stage II and one stage III tumors) followed by deep sequencing validation (average sequencing depth 863x).   Results: All tumors showed clear evidence of spatial ITH. On average, 76% of all mutations and 20/21 known cancer gene mutations were present in all regions of individual tumors (trunk mutations). Copy number analysis did not show substantial difference in large-scale chromosome aberrations. A canonical KRAS p.G12C mutation was detected in only 1 of 4 tumor regions (branch mutations) at exome depth but detected in all four tumor regions (trunk mutations) at increased sequencing depth. In addition, many heterogeneous branch mutations defined by exome sequencing were detectable in all regions of individual tumors with increasing sequencing depth. Significant differences in mutational spectrum were observed in 6 tumors indicating that specific mutational processes were likely operative at different times during development of these tumors. With a median follow up of 21 months post surgery, 3 patients have relapsed and all 3 patients presented with significantly larger fractions of subclonal mutations in their primary tumors.   Conclusions: Although multi-region sampling is still required to fully assess ITH complexity, single biopsy analysis at appropriate depth might be sufficient to identify the majority of known cancer gene mutations in localized lung adenocarcinomas. Larger subclonal mutation fractions may be associated with increased likelihood of postsurgical relapse in patients with localized lung adenocarcinomas. Studies on larger cohort, ideally with comprehensive clinical annotation and repeat biopsy at relapse are needed to fully understand the clinical impact of ITH.","study_type":"Other","pubmed_ids":[25301631],"external_links":null,"is_released":true,"released_date":"2014-08-05T21:47:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000931","title":"HipSci_ChIPseq_healthy_volunteers__set_1","description":"The HipSci project brings together diverse constitutents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  We perfom ChIP-seq for H3K4me3, H3K27ac, H3K27me3.","abstract":"The HipSci project brings together diverse constitutents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  We perfom ChIP-seq for H3K4me3, H3K27ac, H3K27me3.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000932","title":"Genetic Landscape of Esophageal Squamous Cell Carcinoma Defined by Exome Sequencing on Chinese Patient Cohort and Cell Lines","description":"Esophageal Squamous Cell Carcinoma (ESCC) is one of the deadliest cancers worldwide. To define the genetic landscape of ESCC, whole exome sequencing was performed on 113 pairs of tumor and normal DNA samples collected from Chinese individuals with treatment-naive primary ESCC, along with 8 cell lines, including 7 from KYSE series ESCC cell lines and one immortalized esophageal squamous epithelial cell line Het-1A.","abstract":"Esophageal Squamous Cell Carcinoma (ESCC) is one of the deadliest cancers worldwide. To define the genetic landscape of ESCC, whole exome sequencing was performed on 113 pairs of tumor and normal DNA samples collected from Chinese individuals with treatment-naive primary ESCC, along with 8 cell lines, including 7 from KYSE series ESCC cell lines and one immortalized esophageal squamous epithelial cell line Het-1A.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-08-06T03:48:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000933","title":"Multi-omics analysis defines core genomic alterations in pheochromocytomas and paragangliomas","description":"Pheochromocytomas (PCC) and paragangliomas (PGL) are neural crest-derived tumors. We performed the integrated genomic analysis of a collection of PCC/PGL from the French COMETE network using SNP arrays, whole-exome sequencing, DNA methylation arrays, mRNA expression arrays and miRNA sequencing. We found that PCC/PGL are characterized by a low mutation rate, with few recurrent somatic mutations and focal copy number alterations (CNAs). In contrast, we detected recurrent broad CNAs strongly associated with known molecular groups, often leading to the biallelic inactivation of the known susceptibility genes of PCC/PGL. We also identified DNA methylation changes and miRNA expression clusters strongly associated with molecular groups. Of note, overexpression of the miRNA cluster 182/96/183 is specific of SDHB-mutated tumors and induces invasive traits, whereas silencing of the imprinted DLK1-MEG3 miRNA cluster due to a loss of heterozygosity of the 14q32.2 locus is a potential driver in a subset of sporadic tumors. This comprehensive analysis illustrates the functional interdependence between genomic and epigenomic dysregulations underlying PCC/PGL.","abstract":"Pheochromocytomas (PCC) and paragangliomas (PGL) are neural crest-derived tumors. We performed the integrated genomic analysis of a collection of PCC/PGL from the French COMETE network using SNP arrays, whole-exome sequencing, DNA methylation arrays, mRNA expression arrays and miRNA sequencing. We found that PCC/PGL are characterized by a low mutation rate, with few recurrent somatic mutations and focal copy number alterations (CNAs). In contrast, we detected recurrent broad CNAs strongly associated with known molecular groups, often leading to the biallelic inactivation of the known susceptibility genes of PCC/PGL. We also identified DNA methylation changes and miRNA expression clusters strongly associated with molecular groups. Of note, overexpression of the miRNA cluster 182/96/183 is specific of SDHB-mutated tumors and induces invasive traits, whereas silencing of the imprinted DLK1-MEG3 miRNA cluster due to a loss of heterozygosity of the 14q32.2 locus is a potential driver in a subset of sporadic tumors. This comprehensive analysis illustrates the functional interdependence between genomic and epigenomic dysregulations underlying PCC/PGL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-08-07T09:16:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000934","title":"PREDICT___Whole_Genomes","description":"PREDICT/Predicting individual response and resistance to VEGFR/mTOR pathway therapeutic intervention using biomarkers discovered through tumour functional genomics.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina massively parallel sequencing technology, we aim to sequence microRNAs plus the protein coding genome of a number of samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-08-07T09:26:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000935","title":"Single_Cell_Sequencing_of_Sperm__scSperm_","description":"The aim of this project is to genotype and sequence single spermatozoa from two men, one in his twenties and the other in his seventies. The resulting data is used to quantify the mutations that have arisen in the gametes of both individuals in order to better understand the effect of aging on mutation rates and modes.Project Outline. In order to quantify mutations, semen from two individuals are sequenced. 48 single sperm cells are isolated from each individual, and their DNA is extracted. The resulting genomes are amplified using PicoPlex, GenomiPhi MDA, Repli-G MDA, and MALBAC. QC step is applied to check the quality of WGA DNA using standard Sequenom plex (26 SNPs). A subset of 32 amplification products which pass the intiall QC, are genotyped using Affymetrix SNP6 chips. 12 of the genotyped amplification products are also sequenced. In addition, one multi-cell sample per individual is sequenced as a reference and for validation purposes.Altogether, 12 single cell sperm genomes and two multi-cell genomes are sequenced, coming to a total of 14 genomes. Of the single cell sperm genomes, 2 are sequenced to 50x coverage, and the other 10 to 25x coverage. Both multi-cell genomes are sequenced to 25x coverage.","abstract":"The aim of this project is to genotype and sequence single spermatozoa from two men, one in his twenties and the other in his seventies. The resulting data is used to quantify the mutations that have arisen in the gametes of both individuals in order to better understand the effect of aging on mutation rates and modes.Project Outline. In order to quantify mutations, semen from two individuals are sequenced. 48 single sperm cells are isolated from each individual, and their DNA is extracted. The resulting genomes are amplified using PicoPlex, GenomiPhi MDA, Repli-G MDA, and MALBAC. QC step is applied to check the quality of WGA DNA using standard Sequenom plex (26 SNPs). A subset of 32 amplification products which pass the intiall QC, are genotyped using Affymetrix SNP6 chips. 12 of the genotyped amplification products are also sequenced. In addition, one multi-cell sample per individual is sequenced as a reference and for validation purposes.Altogether, 12 single cell sperm genomes and two multi-cell genomes are sequenced, coming to a total of 14 genomes. Of the single cell sperm genomes, 2 are sequenced to 50x coverage, and the other 10 to 25x coverage. Both multi-cell genomes are sequenced to 25x coverage.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-08-08T14:45:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000936","title":"Ischemic stroke in a Swedish case-control study.","description":"Background. Genetic risk scores (GRS), summing up the total effect of several single nucleotide polymorphisms (SNPs) in genes associated with either coronary risk or cardiovascular risk factors, have been tested for association with ischemic stroke with conflicting results. Recently an association was found between a GRS, based on 29 SNPs discovered by genome-wide association studies (GWAS) and hypertension. The aim of our study was to investigate the possible association of the same GRS with ischemic stroke on top of other “traditional risk factors”, also testing its potential improvement in indices of discrimination and reclassification, in a Swedish case-control study. Methods and  results. Twenty-nine SNPs were genotyped in 3,677 stroke cases and 2,415 controls included in the Lund Stroke Register (LSR), the Malmö Diet and Cancer (MDC) study and the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). The analysis was conducted in the entire material, and separately for the three samples.   After adjustment for hypertension, diabetes mellitus and smoking habits, the GRS was associated with ischemic stroke in the entire material [OR (95% CI) 1.086 (1.029-1.147) per SD increase in the GRS p=0.003] with similar trends in all three samples; LSR [1.050 (0.967-1.140)]; p=0.25], MDC [1.168 (1.060-1.288); p=0.002] and SAHLSIS [1.124 (0.997-1.267); P=0.055]. Measures of discrimination and reclassification improved marginally using the GRS. Conclusions. A blood pressure GRS is independently associated with ischemic stroke risk in three Swedish case-control studies, however, the effect size is low and adds marginally to prediction of stroke on top of traditional risk factors including hypertension.","abstract":"Background. Genetic risk scores (GRS), summing up the total effect of several single nucleotide polymorphisms (SNPs) in genes associated with either coronary risk or cardiovascular risk factors, have been tested for association with ischemic stroke with conflicting results. Recently an association was found between a GRS, based on 29 SNPs discovered by genome-wide association studies (GWAS) and hypertension. The aim of our study was to investigate the possible association of the same GRS with ischemic stroke on top of other “traditional risk factors”, also testing its potential improvement in indices of discrimination and reclassification, in a Swedish case-control study. Methods and  results. Twenty-nine SNPs were genotyped in 3,677 stroke cases and 2,415 controls included in the Lund Stroke Register (LSR), the Malmö Diet and Cancer (MDC) study and the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). The analysis was conducted in the entire material, and separately for the three samples.   After adjustment for hypertension, diabetes mellitus and smoking habits, the GRS was associated with ischemic stroke in the entire material [OR (95% CI) 1.086 (1.029-1.147) per SD increase in the GRS p=0.003] with similar trends in all three samples; LSR [1.050 (0.967-1.140)]; p=0.25], MDC [1.168 (1.060-1.288); p=0.002] and SAHLSIS [1.124 (0.997-1.267); P=0.055]. Measures of discrimination and reclassification improved marginally using the GRS. Conclusions. A blood pressure GRS is independently associated with ischemic stroke risk in three Swedish case-control studies, however, the effect size is low and adds marginally to prediction of stroke on top of traditional risk factors including hypertension.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-08-10T06:42:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000937","title":"A study of anterior uveitis using Immunochip","description":"This study used the Illumina Immunochip microarray to investigate the genetic associations of anterior uveitis both in those with ankylosing spondylitis and those without.","abstract":"This study used the Illumina Immunochip microarray to investigate the genetic associations of anterior uveitis both in those with ankylosing spondylitis and those without.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000938","title":"Whole Exome Sequencing of healthy Spanish individuals","description":"The need for a detailed catalogue of local variability for the study of rare diseases within the context of the Medical Genome Project motivated the whole exome sequencing of 267 unrelated individuals, representative of the healthy Spanish population.","abstract":"The need for a detailed catalogue of local variability for the study of rare diseases within the context of the Medical Genome Project motivated the whole exome sequencing of 267 unrelated individuals, representative of the healthy Spanish population.","study_type":"Other","pubmed_ids":[25261458,26764160],"external_links":null,"is_released":true,"released_date":"2014-08-11T07:38:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000939","title":"65 prostate cancer cases WGS and transcriptome sequencing project","description":"We obtained whole-genome and transcriptome sequencing of tumor-benign pairs from 65 Asian prostate cancer (PCa) patients. Taken together with the TCGA PCa cohort, our integration analysis provides the first comprehensive mutational landscape of PCas across major ethnics worldwide and reveals potential novel role of frequent altered chromatin remodeler genes in PCas without androgen receptor (AR) alteration and complex rearrangements derived from Chromoplexy. In addition, we identified 5 putative tumor suppressor genes (TSGs) chains including one on chromosome 13q with novel findings of PCDH9 (deletions in 15/65 tumors) which was implicated in aggressive progression of prostate cancer. Finally, the integrative pathway and co-expression network analysis followed by the functional study indicated the frequent altered genes, particularly focal amplifications of PLXNA1 (11/65), in semaphoring signaling of axon guidance pathway may interact with PI3K/AKT and AR signaling and also contribute to the aggressiveness and progression of prostate cancer.","abstract":"We obtained whole-genome and transcriptome sequencing of tumor-benign pairs from 65 Asian prostate cancer (PCa) patients. Taken together with the TCGA PCa cohort, our integration analysis provides the first comprehensive mutational landscape of PCas across major ethnics worldwide and reveals potential novel role of frequent altered chromatin remodeler genes in PCas without androgen receptor (AR) alteration and complex rearrangements derived from Chromoplexy. In addition, we identified 5 putative tumor suppressor genes (TSGs) chains including one on chromosome 13q with novel findings of PCDH9 (deletions in 15/65 tumors) which was implicated in aggressive progression of prostate cancer. Finally, the integrative pathway and co-expression network analysis followed by the functional study indicated the frequent altered genes, particularly focal amplifications of PLXNA1 (11/65), in semaphoring signaling of axon guidance pathway may interact with PI3K/AKT and AR signaling and also contribute to the aggressiveness and progression of prostate cancer.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001000940","title":"Whole genome study of Hurthle cell thyroid carcinoma","description":"Oncocytic thyroid carcinoma, also known as Hürthle cell thyroid carcinoma, accounts for only a small percentage of all thyroid cancers. However, this malignancy often presents at an advanced stage and poses unique challenges to patients and clinicians. Surgical resection of the tumor accompanied in some cases by radioactive iodine treatment, radiation and chemotherapy are the established modes of therapy. Knowledge of the perturbed oncogenic pathways can provide better understanding of the mechanism of disease and thus opportunities for more effective clinical management. Initially, two oncocytic thyroid carcinomas and their matched normal tissues were profiled using whole genome sequencing. Subsequently, 72 oncocytic thyroid carcinomas, one cell line and 5 Hürthle cell adenomas were examined by targeted sequencing for the presence of mutations in multiple endocrine neoplasia I (MEN1) gene. We report the identification of MEN1 loss-of-function mutations in approximately 7% of patients diagnosed with oncocytic thyroid carcinoma. Whole genome sequence data also revealed large regions of copy number variation encompassing nearly the entire genomes of these tumours. Menin, a ubiquitously expressed nuclear protein, is a well-characterized tumor suppressor whose loss is the cause of multiple endocrine neoplasia type 1 syndrome. Menin is involved in several major cellular pathways such as regulation of transcription, control of cell cycle, apoptosis and DNA damage repair pathways. Mutations of this gene in a subset of Hürthle cell tumors point to a potential role for this protein and its associated pathways in thyroid tumorigenesis.","abstract":"Oncocytic thyroid carcinoma, also known as Hürthle cell thyroid carcinoma, accounts for only a small percentage of all thyroid cancers. However, this malignancy often presents at an advanced stage and poses unique challenges to patients and clinicians. Surgical resection of the tumor accompanied in some cases by radioactive iodine treatment, radiation and chemotherapy are the established modes of therapy. Knowledge of the perturbed oncogenic pathways can provide better understanding of the mechanism of disease and thus opportunities for more effective clinical management. Initially, two oncocytic thyroid carcinomas and their matched normal tissues were profiled using whole genome sequencing. Subsequently, 72 oncocytic thyroid carcinomas, one cell line and 5 Hürthle cell adenomas were examined by targeted sequencing for the presence of mutations in multiple endocrine neoplasia I (MEN1) gene. We report the identification of MEN1 loss-of-function mutations in approximately 7% of patients diagnosed with oncocytic thyroid carcinoma. Whole genome sequence data also revealed large regions of copy number variation encompassing nearly the entire genomes of these tumours. Menin, a ubiquitously expressed nuclear protein, is a well-characterized tumor suppressor whose loss is the cause of multiple endocrine neoplasia type 1 syndrome. Menin is involved in several major cellular pathways such as regulation of transcription, control of cell cycle, apoptosis and DNA damage repair pathways. Mutations of this gene in a subset of Hürthle cell tumors point to a potential role for this protein and its associated pathways in thyroid tumorigenesis.","study_type":"Other","pubmed_ids":[25625803],"external_links":null,"is_released":true,"released_date":"2014-08-12T23:06:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000941","title":"Genomic analyses of gynecologic carcinosarcomas reveal frequent mutations in chromatin remodeling genes","description":"Malignant Mixed Müllerian Tumors, also known as carcinosarcomas, are rare tumors of gynecological origin.  Here we perform whole exome analyses of 22 tumors using massively parallel sequencing to determine the mutational landscape of this tumor type.  On average, we identify 43 mutations per tumor, excluding four cases with a mutator phenotype that harbored inactivating mutations in mismatch repair genes.  In addition to mutations in TP53 and KRAS, we identify genetic alterations in chromatin remodeling genes, ARID1A and ARID1B, in histone methyltransferase MLL3, in histone deacetylase modifier SPOP, and in chromatin assembly factor BAZ1A, in nearly two thirds of cases.  Alterations in genes with potential clinical utility are observed in more than three quarters of the cases and included members of the PI 3-kinase and homologous DNA repair pathways.  These findings highlight the importance of the dysregulation of chromatin remodeling in carcinosarcoma tumorigenesis and suggest new avenues for personalized therapy.","abstract":"Malignant Mixed Müllerian Tumors, also known as carcinosarcomas, are rare tumors of gynecological origin.  Here we perform whole exome analyses of 22 tumors using massively parallel sequencing to determine the mutational landscape of this tumor type.  On average, we identify 43 mutations per tumor, excluding four cases with a mutator phenotype that harbored inactivating mutations in mismatch repair genes.  In addition to mutations in TP53 and KRAS, we identify genetic alterations in chromatin remodeling genes, ARID1A and ARID1B, in histone methyltransferase MLL3, in histone deacetylase modifier SPOP, and in chromatin assembly factor BAZ1A, in nearly two thirds of cases.  Alterations in genes with potential clinical utility are observed in more than three quarters of the cases and included members of the PI 3-kinase and homologous DNA repair pathways.  These findings highlight the importance of the dysregulation of chromatin remodeling in carcinosarcoma tumorigenesis and suggest new avenues for personalized therapy.","study_type":"Other","pubmed_ids":[25233892],"external_links":null,"is_released":true,"released_date":"2014-08-14T23:39:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000942","title":"Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer","description":"Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local recurrence, and another case of cross-metastatic site seeding combining with dynamic remoulding of subclonal mixtures in response to therapy. By ultra-deep sequencing end-stage blood, we detect both metastatic and primary tumour clones, even years after removal of the prostate. Analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations, and additional sequencing of metastases from 19 patients demonstrates that acquisition of TP53 mutations is linked with the expansion of subclones with metastatic potential which we can detect in the blood.","abstract":"Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local recurrence, and another case of cross-metastatic site seeding combining with dynamic remoulding of subclonal mixtures in response to therapy. By ultra-deep sequencing end-stage blood, we detect both metastatic and primary tumour clones, even years after removal of the prostate. Analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations, and additional sequencing of metastases from 19 patients demonstrates that acquisition of TP53 mutations is linked with the expansion of subclones with metastatic potential which we can detect in the blood.","study_type":"Other","pubmed_ids":[25827447],"external_links":null,"is_released":true,"released_date":"2014-08-15T04:50:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000943","title":"Genomic analysis of seminomas","description":"This study looks at the genomic landscape of seminomas, based on exome sequencing data and SNP array data. Eight seminoma tumors and their matched normal DNAs were exome sequenced on Illumina platforms. The same samples were also processed on Affymetrix SNP 6.0 arrays.","abstract":"This study looks at the genomic landscape of seminomas, based on exome sequencing data and SNP array data. Eight seminoma tumors and their matched normal DNAs were exome sequenced on Illumina platforms. The same samples were also processed on Affymetrix SNP 6.0 arrays.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-08-18T10:10:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000945","title":"Utilization of genomic information to augment chemotherapy decision-making for people with incurable malignancies","description":"Most systemic therapies are chosen on the basis of large randomized clinical trials; however, tumour heterogeneity means that cancers with similar histological features may have substantially different underlying biological drivers. The investigators propose that applying personal genomic information prospectively obtained in a clinically realistic timeframe to assist in chemotherapy decision-making could result in more effective and efficient cancer treatment. This study will investigate this approach in a cross section of advanced cancers to examine timeliness, deliverability, rate of actionable targets identified, and our ability to expand this approach into a larger clinical trial setting.","abstract":"Most systemic therapies are chosen on the basis of large randomized clinical trials; however, tumour heterogeneity means that cancers with similar histological features may have substantially different underlying biological drivers. The investigators propose that applying personal genomic information prospectively obtained in a clinically realistic timeframe to assist in chemotherapy decision-making could result in more effective and efficient cancer treatment. This study will investigate this approach in a cross section of advanced cancers to examine timeliness, deliverability, rate of actionable targets identified, and our ability to expand this approach into a larger clinical trial setting.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001000946","title":"Mechanisms_of_patient_response_to_Dabrafenib_in_Melanoma","description":"Samples will be from the BRF113683 (BREAK-3) study which is a Phase III Randomized, Open-label Study Comparing GSK2118436 to Dacarbazine (DTIC) in Previously Untreated Subjects With BRAF Mutation Positive Advanced (Stage III) or Metastatic (Stage IV) Melanoma (n=250 enrolled)•NGS [Agilent capture (Sanger V2 panel): 360 genes and 20 gene fusions; Illumina HiSEQ Sequencing]•CNV: [via NGS or Affy SNP 6.0 or Illumina Omni (TBD)]Bioinformatics: Analysis will be performed using core Sanger informatics pipelines similar to those previously described (Papaemmanuil E et al. (2013) Blood. 22:3616 -3627).   Briefly, copy number analysis will be performed using the ASCAT algorithm, and base substitutions, small insertions and deletions using the CAVEMAN and Pindel algorithms, respectively.  Statistical approaches including generalized linear models will be used to predict clinical variables such as maximum clinical response and duration of response using genetic data.  Sanger and EBI to conduct analysis; Raw data and correlation with clinical endpoints to be analyzed by both EBI/Sanger and GSK (unique pipeline analyses to increase call confidence)","abstract":"To Discover mechanisms of patient response/resistance associated with Dabrafenib monotherapy treatment to identify additional patient selection markers and inform potential rational combinations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-08-22T11:27:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000947","title":"ATAC_SEQ_MAIN___PHASE_1","description":"This is a study to test ATAC-seq protocols. CD4+ and CD8+ cells have been obtained from three different anatomical compartments. We aim to assay open-chromatin regions across these cells and perform comparative analyses.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This is a study to test ATAC-seq protocols. CD4+ and CD8+ cells have been obtained from three different anatomical compartments. We aim to assay open-chromatin regions across these cells and perform comparative analyses.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-08-23T08:59:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000948","title":"DKFZ-HIPO Project H021/NCT MASTER","description":"Clinical genome and transcriptome sequencing in younger adults with advanced-stage cancer across all histologies: DKFZ-HIPO Project H021 (http://www.hipo-heidelberg.org/hipo2/index.php/menu-item-2/32-021-prospective-genetic-characterization-of-tumors-from-individual-patients-of-special-interest) / NCT MASTER (http://www.nct-heidelberg.de/forschung/nct-master.html)","abstract":"Clinical genome and transcriptome sequencing in younger adults with advanced-stage cancer across all histologies: DKFZ-HIPO Project H021 (http://www.hipo-heidelberg.org/hipo2/index.php/menu-item-2/32-021-prospective-genetic-characterization-of-tumors-from-individual-patients-of-special-interest) / NCT MASTER (http://www.nct-heidelberg.de/forschung/nct-master.html)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-08-26T12:25:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000949","title":"Clinical and Molecular Investigation of Familial CEBPA-mutated Acute Myeloid Leukaemia","description":"Myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) are clonal diseases arising from the sequential acquisition of genetic aberrations in haematopoietic stem cells.  Whilst the aetiology is predominantly sporadic, rare reports describe the autosomal dominant inheritance of MDS and AML (familial MDS/AML), often presenting in younger patients (&lt;40 years of age) with a germline mutation in one of three haematopoietic transcription factors: RUNX1, CEBPA and GATA2. The clinical recognition of familial disease can be challenging due to wide variations in phenotype, latency and transmission, complicated further by the patients’ awareness and reporting of affected relatives. Distinct clinical manifestations have however been reported for each genetic subtype and whilst RUNX1 and GATA2 mutations can harbour prolonged dysplastic or cytopenic phases, germline CEBPA mutations universally present with AML de novo. Our group were the first to describe germline CEBPA mutations in 3 related individuals, all of whom developed AML between 10-30 years of age.  The initial pedigree together with those described in the intervening period, were predominantly isolated case reports with limited follow up, hence long term outcomes for this group of patients remain poorly defined. This contrasts with CEBPA mutations occurring in 10-15% of sporadic AML with normal karytoype (NK-AML), where double mutations (CEBPAdm, found in approximately 50% of all CEBPA-AML) are considered a unique molecular entity, associated with favourable clinical outcomes.  In sporadic and familial CEBPAdm AML, N’ terminal mutations enforce translation of the shorter P30-kDa isoform and are typically accompanied by C’ terminal insertions or deletions (disrupting the DNA-binding and/or Leucine zipper domains). Definition of the full molecular landscape awaits extensive whole exome sequencing, although GATA2 mutations (targeting the Zinc Finger 1, ZF1, domain) have been reported in 20-40% of sporadic CEBPAdm AML and recent targeted resequencing analysis revealed a further association with WT1 mutations.  With minimal clinical and molecular information available for familial CEBPA-AML, we are often consulted regarding the management of this unique patient population. To address this need, we have investigated a multi-centre cohort of families with germline CEBPA mutations, providing extended clinical follow up, whole exome profiling of secondary mutations and molecular analysis of relapsed disease.","abstract":"Myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) are clonal diseases arising from the sequential acquisition of genetic aberrations in haematopoietic stem cells.  Whilst the aetiology is predominantly sporadic, rare reports describe the autosomal dominant inheritance of MDS and AML (familial MDS/AML), often presenting in younger patients (&lt;40 years of age) with a germline mutation in one of three haematopoietic transcription factors: RUNX1, CEBPA and GATA2. The clinical recognition of familial disease can be challenging due to wide variations in phenotype, latency and transmission, complicated further by the patients’ awareness and reporting of affected relatives. Distinct clinical manifestations have however been reported for each genetic subtype and whilst RUNX1 and GATA2 mutations can harbour prolonged dysplastic or cytopenic phases, germline CEBPA mutations universally present with AML de novo. Our group were the first to describe germline CEBPA mutations in 3 related individuals, all of whom developed AML between 10-30 years of age.  The initial pedigree together with those described in the intervening period, were predominantly isolated case reports with limited follow up, hence long term outcomes for this group of patients remain poorly defined. This contrasts with CEBPA mutations occurring in 10-15% of sporadic AML with normal karytoype (NK-AML), where double mutations (CEBPAdm, found in approximately 50% of all CEBPA-AML) are considered a unique molecular entity, associated with favourable clinical outcomes.  In sporadic and familial CEBPAdm AML, N’ terminal mutations enforce translation of the shorter P30-kDa isoform and are typically accompanied by C’ terminal insertions or deletions (disrupting the DNA-binding and/or Leucine zipper domains). Definition of the full molecular landscape awaits extensive whole exome sequencing, although GATA2 mutations (targeting the Zinc Finger 1, ZF1, domain) have been reported in 20-40% of sporadic CEBPAdm AML and recent targeted resequencing analysis revealed a further association with WT1 mutations.  With minimal clinical and molecular information available for familial CEBPA-AML, we are often consulted regarding the management of this unique patient population. To address this need, we have investigated a multi-centre cohort of families with germline CEBPA mutations, providing extended clinical follow up, whole exome profiling of secondary mutations and molecular analysis of relapsed disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-08-28T17:52:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000950","title":"Whole exome and transcriptome sequencing of biliary tract cancer","description":"To uncover the full repertoire of genetic and transcriptomic landscape of biliary tract cancer (BTC), we molecularly characterized BTC based on genetic and transcriptomic alteration profiles.","abstract":"To uncover the full repertoire of genetic and transcriptomic landscape of biliary tract cancer (BTC), we molecularly characterized BTC based on genetic and transcriptomic alteration profiles.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-08-29T05:55:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000951","title":"BLUEPRINT ChIP-seq of Epigenetic programming during monocyte to macrophage differentiation and trained innate immunity","description":"Monocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. Transcriptomes and epigenomes in four primary cell types: monocytes, in vitro differentiated naïve, tolerized and trained macrophages were characterized. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and pathways functionally implicated in trained immunity were identified. Strikingly, β-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in DNase I hypersensitive sites at cell-type specific epigenetic loci unveiled differentiation and treatment specific repertoires. Altogether, this study provides a resource to understand the epigenetic changes that underlie innate immunity in humans.","abstract":"Monocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. Transcriptomes and epigenomes in four primary cell types: monocytes, in vitro differentiated naïve, tolerized and trained macrophages were characterized. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and pathways functionally implicated in trained immunity were identified. Strikingly, β-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in DNase I hypersensitive sites at cell-type specific epigenetic loci unveiled differentiation and treatment specific repertoires. Altogether, this study provides a resource to understand the epigenetic changes that underlie innate immunity in humans.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-08-29T11:13:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000952","title":"Dynamics of genomic clones in breast cancer patient xenografts at single cell resolution","description":"Human cancers, including breast cancers, are comprised of clones differing in mutation content that evolve dynamically in space and time following principles of Darwinian evolution, underpinning important emergent features such as drug resistance and metastasis. Human breast cancer xenoengraftment is used as a means of capturing and studying tumour biology, and breast tumour xenografts are generally assumed to be reasonable models of the originating tumours. However the consequences and reproducibility of engraftment and propagation on the genomic clonal architecture of tumours has not been systematically examined at single cell resolution. Here we show by both deep genome and single cell sequencing methods, the clonal dynamics of initial engraftment and subsequent serial propagation of primary and metastatic human breast cancers in immunodeficient mice. In all cases examined, clonal selection on engraftment was observed in both primary and metastatic breast tumours, varying in degree from extreme selective engraftment of minor (&lt;5% of starting population) clones to moderate, polyclonal engraftment. Furthermore, ongoing clonal dynamics during serial passaging is a feature of tumours experiencing modest initial selection. Through single cell sequencing, we show that major mutation clusters estimated from tumour population sequencing relate predictably to the most abundant clonal genotypes, even in clonally complex and rapidly evolving cases. Finally, we show that similar clonal expansion patterns can emerge in independent grafts of the same starting tumour population, indicating that genomic aberrations can be reproducible determinants of evolutionary trajectories. Our results show that measurement of genomically defined clonal population dynamics will be highly informative for functional studies utilizing patient-derived breast cancer xenoengraftment.","abstract":"Human cancers, including breast cancers, are comprised of clones differing in mutation content that evolve dynamically in space and time following principles of Darwinian evolution, underpinning important emergent features such as drug resistance and metastasis. Human breast cancer xenoengraftment is used as a means of capturing and studying tumour biology, and breast tumour xenografts are generally assumed to be reasonable models of the originating tumours. However the consequences and reproducibility of engraftment and propagation on the genomic clonal architecture of tumours has not been systematically examined at single cell resolution. Here we show by both deep genome and single cell sequencing methods, the clonal dynamics of initial engraftment and subsequent serial propagation of primary and metastatic human breast cancers in immunodeficient mice. In all cases examined, clonal selection on engraftment was observed in both primary and metastatic breast tumours, varying in degree from extreme selective engraftment of minor (&lt;5% of starting population) clones to moderate, polyclonal engraftment. Furthermore, ongoing clonal dynamics during serial passaging is a feature of tumours experiencing modest initial selection. Through single cell sequencing, we show that major mutation clusters estimated from tumour population sequencing relate predictably to the most abundant clonal genotypes, even in clonally complex and rapidly evolving cases. Finally, we show that similar clonal expansion patterns can emerge in independent grafts of the same starting tumour population, indicating that genomic aberrations can be reproducible determinants of evolutionary trajectories. Our results show that measurement of genomically defined clonal population dynamics will be highly informative for functional studies utilizing patient-derived breast cancer xenoengraftment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-08-29T19:29:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000953","title":"BLUEPRINT RNA-seq of Epigenetic programming during monocyte to macrophage differentiation and trained innate immunity","description":"Monocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. Transcriptomes and epigenomes in four primary cell types: monocytes, in vitro differentiated naïve, tolerized and trained macrophages were characterized. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and pathways functionally implicated in trained immunity were identified. Strikingly, β-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in DNase I hypersensitive sites at cell-type specific epigenetic loci unveiled differentiation and treatment specific repertoires. Altogether, this study provides a resource to understand the epigenetic changes that underlie innate immunity in humans.","abstract":"Monocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. Transcriptomes and epigenomes in four primary cell types: monocytes, in vitro differentiated naïve, tolerized and trained macrophages were characterized. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and pathways functionally implicated in trained immunity were identified. Strikingly, β-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in DNase I hypersensitive sites at cell-type specific epigenetic loci unveiled differentiation and treatment specific repertoires. Altogether, this study provides a resource to understand the epigenetic changes that underlie innate immunity in humans.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-09-01T08:56:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000954","title":"BLUEPRINT DNase accessibility of Epigenetic programming during monocyte to macrophage differentiation and trained innate immunity","description":"Monocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. Transcriptomes and epigenomes in four primary cell types: monocytes, in vitro differentiated naïve, tolerized and trained macrophages were characterized. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and pathways functionally implicated in trained immunity were identified. Strikingly, β-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in DNase I hypersensitive sites at cell-type specific epigenetic loci unveiled differentiation and treatment specific repertoires. Altogether, this study provides a resource to understand the epigenetic changes that underlie innate immunity in humans.","abstract":"Monocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. Transcriptomes and epigenomes in four primary cell types: monocytes, in vitro differentiated naïve, tolerized and trained macrophages were characterized. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and pathways functionally implicated in trained immunity were identified. Strikingly, β-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in DNase I hypersensitive sites at cell-type specific epigenetic loci unveiled differentiation and treatment specific repertoires. Altogether, this study provides a resource to understand the epigenetic changes that underlie innate immunity in humans.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-09-01T08:57:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000955","title":"EBV_AID_project","description":"Whole genome sequencing of EBV-transformed B cells in order to determine whether EBV induction of activation-induced cytidine deaminase (AID) produces genome-wide mutations and/or chromosomal rearrangements.","abstract":"Whole genome sequencing of EBV-transformed B cells in order to determine whether EBV induction of activation-induced cytidine deaminase (AID) produces genome-wide mutations and/or chromosomal rearrangements.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-09-03T13:57:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000956","title":"Comprehensive_Molecular_Characterization_of_Colorectal_Cancer_Metastases__MOSAIC_","description":"Systematic next-generation sequencing efforts are beginning to define the genomic landscape across a range of primary tumours, but we know very little of the mutational evolution that contributes to the disease progression.We therefore propose to obtain a comprehensive description of genomic, transcriptomic and epigenomic changes in a cohort of 100 matched primary and metastatic colorectal cancers, and additionally to explore the extent to which those mutations identified as recurrent in the metastatic setting are able to subvert normal biological processes using both genetically engineered mouse models and established cancer cell lines. This study will also enable us to define to what extent primary tumour profiling can capture the biological processes operative in matched metastases as well as the significance of intratumoural heterogeneity.","abstract":"Systematic next-generation sequencing efforts are beginning to define the genomic landscape across a range of primary tumours, but we know very little of the mutational evolution that contributes to the disease progression.We therefore propose to obtain a comprehensive description of genomic, transcriptomic and epigenomic changes in a cohort of 100 matched primary and metastatic colorectal cancers, and additionally to explore the extent to which those mutations identified as recurrent in the metastatic setting are able to subvert normal biological processes using both genetically engineered mouse models and established cancer cell lines. This study will also enable us to define to what extent primary tumour profiling can capture the biological processes operative in matched metastases as well as the significance of intratumoural heterogeneity.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000957","title":"Germline variants in the SEMA4A gene predispose to familial colorectal cancer type X","description":"Familial colorectal cancer type X (FCCTX) is characterized by clinical features of hereditary non-polyposis colorectal cancer with a yet undefined genetic background. Here, using an integrative genomics strategy, we identify the SEMA4A p.Val78Met germline mutation in an Austrian kindred with FCCTX. Compared with wild-type protein, SEMA4AV78M demonstrates significantly increased MAPK/Erk and PI3K/Akt signaling as well as cell cycle progression of SEMA4A deficient HCT-116 colorectal cancer cells. In a cohort of 53 patients with FCCTX we depict two further SEMA4A mutations, p.Gly484Ala and p.Ser326Phe, and the single nucleotide polymorphism (SNP) p.Pro682Ser. This SNP is highly associated with the FCCTX phenotype exhibiting increased risk for colorectal cancer (OR 6.79, 95% CI 2.63 to 17.52). Our study shows previously unidentified germline variants in SEMA4A predisposing to FCCTX which has implications for surveillance strategies of patients and their families.","abstract":"Familial colorectal cancer type X (FCCTX) is characterized by clinical features of hereditary non-polyposis colorectal cancer with a yet undefined genetic background. Here, using an integrative genomics strategy, we identify the SEMA4A p.Val78Met germline mutation in an Austrian kindred with FCCTX. Compared with wild-type protein, SEMA4AV78M demonstrates significantly increased MAPK/Erk and PI3K/Akt signaling as well as cell cycle progression of SEMA4A deficient HCT-116 colorectal cancer cells. In a cohort of 53 patients with FCCTX we depict two further SEMA4A mutations, p.Gly484Ala and p.Ser326Phe, and the single nucleotide polymorphism (SNP) p.Pro682Ser. This SNP is highly associated with the FCCTX phenotype exhibiting increased risk for colorectal cancer (OR 6.79, 95% CI 2.63 to 17.52). Our study shows previously unidentified germline variants in SEMA4A predisposing to FCCTX which has implications for surveillance strategies of patients and their families.","study_type":"Other","pubmed_ids":[25307848],"external_links":null,"is_released":true,"released_date":"2014-09-04T19:48:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000958","title":"TGS___Comprehensive_Molecular_Characterization_of_Colorectal_Cancer_Metastases__MOSAIC_","description":"Systematic next generation sequencing efforts are beginning to define the genomic landscape across a range of primary tumours, but we know very little of the mutational evolution that contributes to disease progression.We therefore propose to obtain a comprehensive description of genomic, transcriptomic and epigenomic changes in a cohort of matched primary and metastatic colorectal cancers, and additionally to explore the extent to which those mutations identified as recurrent in the metastatic setting are able to subvert normal biological processes using both genetically engineered mouse models and established cancer cell lines. This study will enable us to define to what extent primary tumour profiling can capture the biological processes operative in matched metastases as well as the significance of intratumoural heterogeneity.","abstract":"Systematic next generation sequencing efforts are beginning to define the genomic landscape across a range of primary tumours, but we know very little of the mutational evolution that contributes to disease progression.We therefore propose to obtain a comprehensive description of genomic, transcriptomic and epigenomic changes in a cohort of matched primary and metastatic colorectal cancers, and additionally to explore the extent to which those mutations identified as recurrent in the metastatic setting are able to subvert normal biological processes using both genetically engineered mouse models and established cancer cell lines. This study will enable us to define to what extent primary tumour profiling can capture the biological processes operative in matched metastases as well as the significance of intratumoural heterogeneity.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-09-05T10:56:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000959","title":"APCDR AGV Project: The African Genome Variation Project(dense array genotyping data)","description":"The African Genome Variation Project (AGVP) aims to provide a global resource to understand population diversity and help design, implement and interpret genomic studies in sub-Saharan Africa (SSA), and worldwide. The AGVP represents dense genotyping data on 1,481 individuals from 18 ethno-linguistic groups and low coverage whole genome sequencing data on 320 individuals from 7 ethno-linguistic groups in SSA.","abstract":"The African Genome Variation Project (AGVP) aims to provide a global resource to understand population diversity and help design, implement and interpret genomic studies in sub-Saharan Africa (SSA), and worldwide. The AGVP represents dense genotyping data on 1,481 individuals from 18 ethno-linguistic groups and low coverage whole genome sequencing data on 320 individuals from 7 ethno-linguistic groups in SSA.","study_type":"Other","pubmed_ids":[25470054],"external_links":null,"is_released":true,"released_date":"2014-09-05T11:48:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000960","title":"APCDR AGV Project: Whole genome sequencing of 3 African populations (curated data)","description":"The African Genome Variation Project (AGVP) provides a resource to help design, implement and interpret genomic studies in sub-Saharan Africa (SSA) and worldwide. The AGVP represents dense genotypes from 1,481 and whole genome sequences (WGS) from 320 individuals across SSA.\nAs part of the AGVP we sequenced 3 African populations; Baganda from Uganda (4x), Zulu from South Africa (4x), Gumuz, Wolayta, Oromo, Somali and Amhara from Ethiopia (8x).","abstract":"The African Genome Variation Project (AGVP) provides a resource to help design, implement and interpret genomic studies in sub-Saharan Africa (SSA) and worldwide. The AGVP represents dense genotypes from 1,481 and whole genome sequences (WGS) from 320 individuals across SSA.\nAs part of the AGVP we sequenced 3 African populations; Baganda from Uganda (4x), Zulu from South Africa (4x), Gumuz, Wolayta, Oromo, Somali and Amhara from Ethiopia (8x).","study_type":"Other","pubmed_ids":[25470054],"external_links":null,"is_released":true,"released_date":"2014-09-05T12:41:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000961","title":"Cross-species genomics identifies TAF12, NFYC and RAD54L as novel choroid plexus carcinoma oncogenes","description":"Choroid plexus carcinomas (CPC) are poorly understood and frequently lethal brain tumors with minimal treatment options.  Using a new mouse model of the disease and a large cohort of human CPCs, we performed a cross-species, genome-wide search for novel oncogenes within syntenic regions of chromosome gain.  TAF12, NFYC and RAD54L, co-located on human chromosome 1p32-35.3 and mouse chromosome 4qD1-D3, were identified as oncogenes that are gained in tumors in both species and required to initiate and progress the disease in mice.  TAF12 and NFYC are transcription factors that regulate the epigenome, while RAD54L plays a central role in DNA repair.  Our data identify a group of concurrently gained, novel oncogenes that cooperate in the formation of CPC and unmask potential new avenues for therapy.","abstract":"Choroid plexus carcinomas (CPC) are poorly understood and frequently lethal brain tumors with minimal treatment options.  Using a new mouse model of the disease and a large cohort of human CPCs, we performed a cross-species, genome-wide search for novel oncogenes within syntenic regions of chromosome gain.  TAF12, NFYC and RAD54L, co-located on human chromosome 1p32-35.3 and mouse chromosome 4qD1-D3, were identified as oncogenes that are gained in tumors in both species and required to initiate and progress the disease in mice.  TAF12 and NFYC are transcription factors that regulate the epigenome, while RAD54L plays a central role in DNA repair.  Our data identify a group of concurrently gained, novel oncogenes that cooperate in the formation of CPC and unmask potential new avenues for therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-09-05T19:31:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000962","title":"Plasma DNA aberrations in systemic lupus erythematosus revealed by genomic and methylomic sequencing","description":"We performed a high-resolution analysis of the biological characteristics of plasma DNA in systemic lupus erythematosus (SLE) patients using massively parallel genomic and methylomic sequencing. A number of plasma DNA abnormalities were found. First, aberrations in measured genomic representations (MGRs) were identified in the plasma DNA of SLE patients. The extent of the aberrations in MGRs correlated with anti-double–stranded DNA (anti-dsDNA) antibody level. Second, the plasma DNA of active SLE patients exhibited skewed molecular size-distribution profiles with a significantly increased proportion of short DNA fragments. The extent of plasma DNA shortening in SLE patients correlated with the SLE disease activity index (SLEDAI) and anti-dsDNA antibody level. Third, the plasma DNA of active SLE patients showed decreased methylation densities. The extent of hypomethylation correlated with SLEDAI and anti-dsDNA antibody level. To explore the impact of anti-dsDNA antibody on plasma DNA in SLE, a column-based protein G capture approach was used to fractionate the IgG-bound and non–IgG-bound DNA in plasma. Compared with healthy individuals, SLE patients had higher concentrations of IgG-bound DNA in plasma. More IgG binding occurs at genomic locations showing increased MGRs. Furthermore, the IgG-bound plasma DNA was shorter in size and more hypomethylated than the non–IgG-bound plasma DNA. These observations have enhanced our understanding of the spectrum of plasma DNA aberrations in SLE and may provide new molecular markers for SLE. Our results also suggest that caution should be exercised when interpreting plasma DNA-based noninvasive prenatal testing and cancer testing conducted for SLE patients.","abstract":"We performed a high-resolution analysis of the biological characteristics of plasma DNA in systemic lupus erythematosus (SLE) patients using massively parallel genomic and methylomic sequencing. A number of plasma DNA abnormalities were found. First, aberrations in measured genomic representations (MGRs) were identified in the plasma DNA of SLE patients. The extent of the aberrations in MGRs correlated with anti-double–stranded DNA (anti-dsDNA) antibody level. Second, the plasma DNA of active SLE patients exhibited skewed molecular size-distribution profiles with a significantly increased proportion of short DNA fragments. The extent of plasma DNA shortening in SLE patients correlated with the SLE disease activity index (SLEDAI) and anti-dsDNA antibody level. Third, the plasma DNA of active SLE patients showed decreased methylation densities. The extent of hypomethylation correlated with SLEDAI and anti-dsDNA antibody level. To explore the impact of anti-dsDNA antibody on plasma DNA in SLE, a column-based protein G capture approach was used to fractionate the IgG-bound and non–IgG-bound DNA in plasma. Compared with healthy individuals, SLE patients had higher concentrations of IgG-bound DNA in plasma. More IgG binding occurs at genomic locations showing increased MGRs. Furthermore, the IgG-bound plasma DNA was shorter in size and more hypomethylated than the non–IgG-bound plasma DNA. These observations have enhanced our understanding of the spectrum of plasma DNA aberrations in SLE and may provide new molecular markers for SLE. Our results also suggest that caution should be exercised when interpreting plasma DNA-based noninvasive prenatal testing and cancer testing conducted for SLE patients.","study_type":"Other","pubmed_ids":[25427797],"external_links":null,"is_released":true,"released_date":"2014-09-06T03:17:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000963","title":"The Druze analysis group","description":"To comprehensively characterize the genetic structure of the Druze population, we recruited and genotyped 40 parent-offspring trios from the Upper Galilee in Israel and the Golan Heights, attempting to capture different extended families (clans) across various geographical locations.","abstract":"To comprehensively characterize the genetic structure of the Druze population, we recruited and genotyped 40 parent-offspring trios from the Upper Galilee in Israel and the Golan Heights, attempting to capture different extended families (clans) across various geographical locations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-09-08T00:18:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000964","title":"Genotyping_of_Cambridge_BioResource_for_BluePrint","description":"Deep epigenetic and transcriptional regulation data across multiple hematopoietic celldevelopment stages exist within BluePrint individuals. However the complimentary genotypedata does not exist. We wish to genotype these individuals with the HumanOmni2.5-8 arrayand impute full genotypes. This will allow us to integrate this dataset with an additionaldataset where we have low coverage epigenetic, RNAseq and methylation data includinggenotype information.","abstract":"Deep epigenetic and transcriptional regulation data across multiple hematopoietic celldevelopment stages exist within BluePrint individuals. However the complimentary genotypedata does not exist. We wish to genotype these individuals with the HumanOmni2.5-8 arrayand impute full genotypes. This will allow us to integrate this dataset with an additionaldataset where we have low coverage epigenetic, RNAseq and methylation data includinggenotype information.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000965","title":"Multiple tumor samples within a primary tumor from a patient with ESCC were obtained and the DNAs were subjected to whole exome sequencing (illumina Hiseq 2000). The mutations and indels were called with bioinformatic tools.","description":"Cancer is a disease of the genome. Many genomic abnormalities have been found in a variety of cancer types, which are believed to be attributable to tumorigenesis as well as resistance to treatment and recurrence. Genomic heterogeneity in the same type of cancer or within a tumor reveals the complexity of cancer biology so that intratumor heterogeneity has become an inherent feature of cancer. In this study, we use whole-exome sequencing and array comparative genomic hybridization technology to examine the mutational profiling and copy number changes from multi-region samples within an esophageal cancer in order to understand the genomic phylogeny in the evolution of intratumor heterogeneity in esophageal cancer.","abstract":"Cancer is a disease of the genome. Many genomic abnormalities have been found in a variety of cancer types, which are believed to be attributable to tumorigenesis as well as resistance to treatment and recurrence. Genomic heterogeneity in the same type of cancer or within a tumor reveals the complexity of cancer biology so that intratumor heterogeneity has become an inherent feature of cancer. In this study, we use whole-exome sequencing and array comparative genomic hybridization technology to examine the mutational profiling and copy number changes from multi-region samples within an esophageal cancer in order to understand the genomic phylogeny in the evolution of intratumor heterogeneity in esophageal cancer.","study_type":"Other","pubmed_ids":[26619400],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000966","title":"A study of ankylosing spondylitis using the Illumina ExomeChip microarray","description":"A study of ankylosing spondylitis using the Illumina ExomeChip microarray.","abstract":"A study of ankylosing spondylitis using the Illumina ExomeChip microarray.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000967","title":"Genetic Landscape of Esophageal Squamous Cell Carcinoma Defined by Exome Sequencin on Chinese Patient Cohort and Cell Lines","description":"Esophageal Squamous Cell Carcinoma (ESCC) is one of the deadliest cancers worldwide. To define the genetic landscape of ESCC, whole exome sequencing was performed on 113 pairs of tumor and normal DNA samples collected from Chinese individuals with treatment-naive primary ESCC, along with 8 cell lines, including 7 from KYSE series ESCC cell lines and one immortalized esophageal squamous epithelial cell line Het-1A","abstract":"Esophageal Squamous Cell Carcinoma (ESCC) is one of the deadliest cancers worldwide. To define the genetic landscape of ESCC, whole exome sequencing was performed on 113 pairs of tumor and normal DNA samples collected from Chinese individuals with treatment-naive primary ESCC, along with 8 cell lines, including 7 from KYSE series ESCC cell lines and one immortalized esophageal squamous epithelial cell line Het-1A","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001000968","title":"Origins and functional consequence of somatic mitochondrial DNA mutations","description":"Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, the origins and impact of cancer-associated mutations in mitochondrial DNA (mtDNA) are unclear. Here, we analysed somatic alterations in mtDNA from 1,675 tumors across 31 histologies. We identified 1,907 somatic substitutions, which exhibited dramatic replicative strand bias, predominantly C&gt;T and A&gt;G on the mitochondrial heavy strand. This strand-asymmetric signature differs from those found in nuclear cancer genomes but matches the inferred germline process shaping primate mtDNA sequence content. Numbers of mtDNA mutations showed considerable heterogeneity across tumor types. Missense mutations were selectively neutral and often gradually drifted towards homoplasmy over time. In contrast, mutations resulting in protein truncation undergo negative selection and were almost exclusively heteroplasmic. Our findings indicate that the endogenous mutational mechanism has far greater impact than any other external mutagens in mitochondria, and is fundamentally linked to mtDNA replication.","abstract":"Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, the origins and impact of cancer-associated mutations in mitochondrial DNA (mtDNA) are unclear. Here, we analysed somatic alterations in mtDNA from 1,675 tumors across 31 histologies. We identified 1,907 somatic substitutions, which exhibited dramatic replicative strand bias, predominantly C&gt;T and A&gt;G on the mitochondrial heavy strand. This strand-asymmetric signature differs from those found in nuclear cancer genomes but matches the inferred germline process shaping primate mtDNA sequence content. Numbers of mtDNA mutations showed considerable heterogeneity across tumor types. Missense mutations were selectively neutral and often gradually drifted towards homoplasmy over time. In contrast, mutations resulting in protein truncation undergo negative selection and were almost exclusively heteroplasmic. Our findings indicate that the endogenous mutational mechanism has far greater impact than any other external mutagens in mitochondria, and is fundamentally linked to mtDNA replication.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-09-10T11:30:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000969","title":"HipSci___Whole_Exome_sequencing___Bardet_Biedl_Syndrome","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bardet-Biedl syndrome","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bardet-Biedl syndrome","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-09-10T12:19:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000970","title":"Sequencing data from a patient with  hypertrophic cardiomyopathy","description":"Study of a family with  hypertrophic cardiomyopathy","abstract":"Study of a family with  hypertrophic cardiomyopathy","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000971","title":"Exome sequencing of 1000 population control samples from the UK 1958 birth cohort","description":"Exome sequencing from 1,000 UK population samples (the ICR1000 Exome series), using samples from the 1958 Birth Cohort Collection, a population-based collection of all individuals born in the UK in one week in 1958 (http://www.cls.ioe.ac.uk).   DNA libraries were prepared from genomic DNA using the Illumina TruSeq sample preparation kit. DNA was fragmented using Covaris technology and the libraries were prepared without gel size selection. Target enrichment was performed in pools of six libraries using the Illumina TruSeq Exome Enrichment kit. The captured DNA libraries were PCR amplified using the supplied paired-end PCR primers. Sequencing was performed with an Illumina HiSeq2000 (v3 flow cell, one pool per lane) generating 2x100-bp reads.","abstract":"Exome sequencing from 1,000 UK population samples (the ICR1000 Exome series), using samples from the 1958 Birth Cohort Collection, a population-based collection of all individuals born in the UK in one week in 1958 (http://www.cls.ioe.ac.uk).   DNA libraries were prepared from genomic DNA using the Illumina TruSeq sample preparation kit. DNA was fragmented using Covaris technology and the libraries were prepared without gel size selection. Target enrichment was performed in pools of six libraries using the Illumina TruSeq Exome Enrichment kit. The captured DNA libraries were PCR amplified using the supplied paired-end PCR primers. Sequencing was performed with an Illumina HiSeq2000 (v3 flow cell, one pool per lane) generating 2x100-bp reads.","study_type":"Other","pubmed_ids":[26834991],"external_links":null,"is_released":true,"released_date":"2014-09-15T09:15:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000972","title":"ChIP-seq Protocol Freiburg","description":"ChIP-seq Protocol Freiburg","abstract":"ChIP-seq Protocol Freiburg","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000973","title":"High coverage target resequencing of coding and regulatory regions of 38 Parkinson disease genes associated either to the Mendelian or the sporadic forms of the disease","description":"Coding sequences and putative regulatory sequences (retrieved from Ensembl and including up to 2500 bp of promoter sequence upstream the transcription start site) were re-sequenced to a mean depth of 49X on 38 genes associated to Parkinson's disease (RAB25, NUCKS1, RAB7L1, GBA, SYT11, ACMSD, STK39, MCCC1, STBD1, GAK, DGKQ, BST1, SCARB2, HLA-DRB5, GPNMB, FGF20, ITGA8, HIP1R, STX1B, SETD1A, SREBF1, MED13, RAI1, MAPT, RIT2, GIGYF2, HTRA2, EIF4G1, SNCA, LRRK2, VPS35, PINK1, DJ1, ATP13A2, UCHL1, PARK2, FBXO7, and PLA2G6). Sequencing was performed on 249 Parkinson's idiopathic cases and 145 unrelated controls of Spanish origin. All sequencing data was generated with an Illumina Hiseq2000 instrument after enrichment with a custom NimbleGen array. Raw reads were mapped to human reference genome hg19/GRCh37 using BWA aligner.","abstract":"Coding sequences and putative regulatory sequences (retrieved from Ensembl and including up to 2500 bp of promoter sequence upstream the transcription start site) were re-sequenced to a mean depth of 49X on 38 genes associated to Parkinson's disease (RAB25, NUCKS1, RAB7L1, GBA, SYT11, ACMSD, STK39, MCCC1, STBD1, GAK, DGKQ, BST1, SCARB2, HLA-DRB5, GPNMB, FGF20, ITGA8, HIP1R, STX1B, SETD1A, SREBF1, MED13, RAI1, MAPT, RIT2, GIGYF2, HTRA2, EIF4G1, SNCA, LRRK2, VPS35, PINK1, DJ1, ATP13A2, UCHL1, PARK2, FBXO7, and PLA2G6). Sequencing was performed on 249 Parkinson's idiopathic cases and 145 unrelated controls of Spanish origin. All sequencing data was generated with an Illumina Hiseq2000 instrument after enrichment with a custom NimbleGen array. Raw reads were mapped to human reference genome hg19/GRCh37 using BWA aligner.","study_type":"Other","pubmed_ids":[25504046],"external_links":null,"is_released":true,"released_date":"2014-09-16T11:00:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000974","title":"Genetic landscape of malignant peripheral nerve sheath tumors","description":"Neurofibromatosis 1 is a hereditary syndrome characterized by the development of numerous benign neurofibromas, a small subset of which progress to malignant peripheral nerve sheath tumors (MPNSTs). To better understand the genetic basis for MPNSTs, we performed whole genome sequencing on four MPNSTs from patients with neurofibromatosis 1 and found that each of them had a somatic, inactivating mutation of SUZ12, a chromatin modifying gene adjacent to the NF1 gene responsible for the benign neurofibromas in these patients. We then performed targeted sequencing on an additional 46 MPNSTs and found that 12 had somatic mutations in SUZ12. Fifteen of the 17 (88%) mutations in SUZ12 were predicted to inactivate protein function, implicating it as a tumor suppressor gene possibly responsible for the progression from neurofibromas to MPNTs.","abstract":"Neurofibromatosis 1 is a hereditary syndrome characterized by the development of numerous benign neurofibromas, a small subset of which progress to malignant peripheral nerve sheath tumors (MPNSTs). To better understand the genetic basis for MPNSTs, we performed whole genome sequencing on four MPNSTs from patients with neurofibromatosis 1 and found that each of them had a somatic, inactivating mutation of SUZ12, a chromatin modifying gene adjacent to the NF1 gene responsible for the benign neurofibromas in these patients. We then performed targeted sequencing on an additional 46 MPNSTs and found that 12 had somatic mutations in SUZ12. Fifteen of the 17 (88%) mutations in SUZ12 were predicted to inactivate protein function, implicating it as a tumor suppressor gene possibly responsible for the progression from neurofibromas to MPNTs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-09-17T19:24:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000975","title":"Signatures of Aristolochic Acid Mutagenesis in Bladder Cancer","description":"This study looks at signatures of Aristolochic Acid mutagenesis in bladder cancer, based on exome and whole genome sequencing data. Thirteen bladder tumors and their matched normal DNAs were sequenced on Illumina platforms. Among them eleven were exome sequenced and two were whole genome sequenced.","abstract":"This study looks at signatures of Aristolochic Acid mutagenesis in bladder cancer, based on exome and whole genome sequencing data. Thirteen bladder tumors and their matched normal DNAs were sequenced on Illumina platforms. Among them eleven were exome sequenced and two were whole genome sequenced.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-09-18T03:53:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000976","title":"Pluripotent_Stem_Cell_Platform__PSCP_","description":"The Biomedical Cell Production Platform (BCPP) will establish, advance and standardiseemerging pluripotent stem cell technologies so as to achieve a leading position in the field ofstem cell product development for clinical trials.Limited availability of human donor tissue is a key issue in regenerative medicine. Thisproblem is particularly pronounced in tissues with restricted regenerative potential such as thenervous system. However, advances in the fields of pluripotent stem cells (PSC) and cellprogramming provide unprecedented opportunities to generate safe donor cells for all humantissues and organs in virtually unlimited numbers. These advances include: (i) the availabilityof clinical grade human embryonic stem cells; (ii) the capability to reprogramme patientsomatic cells into induced pluripotent stem cells (iPSC); (iii) protocols for differentiating orforward programming PSC into therapeutically relevant somatic cell types; (iv) technologiesfor directly converting tissue-specific cells into other somatic cell fates; (v) methods forgenetic modification without collateral damage of the donor cell genome; vi) tools foridentifying and monitoring genetic and epigenetic changes that may have significantconsequences for safety and functional efficacy of PSC and their derivatives. Harnessingthese advances will enable an array of novel cell-mediated therapies. A prerequisite for therealisation of such therapeutic ambitions is a translational structure that melds fundamentaldiscoveries into a pipeline for medical products and applications.BCPP will concentrate in-house activities on PSC and derivative tissue stem cellintermediates. However, the field in general will also benefit from tackling key knowledgegaps including: (i) establishment of standardised systems for the generation of robustgenetically stable human PSC populations suitable for therapeutic translation, (ii)development and implementation of genetic modification tools that bypass the risk ofinsertional mutagenesis and are subject to science-based risk assessment, (iii) developmentof effective, reliable and reproducible differentiation protocols yielding functional and clinicallycompliant tissue-specific donor cells, (iv) quality control systems suitable for consistentmanufacturing of stem cells and differentiated progeny suitable for use in human applications.BCPP will implement a translational research programme to reach the following goals:Tools for monitoring and assessing the significance of genetic and epigenetic variation inPSCs.Qualified methods that minimise the occurrence of functionally significant variants ofundifferentiated ES and iPS cells and their differentiated derivatives during generation andexpansion.Standardised, integration-free and clinically compliant technologies for iPS cell productionand direct cell fate conversion.Technology for large-scale production from PSCs of standardised tissue-specific stem andprogenitor cells suitable for preparation of cell-based medicines.Regulatory compliant procedures and best practice documents for producing safe pluripotentstem cell-derived somatic phenotypes suitable for clinical trials.Added ValueThe combination of WT/MRC Cambridge Stem Cell Institute (SCI), the Sheffield Centre forStem Cell Biology (CSCB), Sanger Institute (WTSI), and Babraham Institute constitutesunmatched strength in the UK for development of enabling technologies in the field of PSCbiology, reprogramming and differentiation. NIBSC-HPA (UK Stem Cell Bank; UKSCB)provides essential complementary input on qualification of cell-based protocols, qualitystandards and regulatory requirements. The BCPP will integrate this combined expertise intogoal-oriented translational programmes and will also develop strategic partnershipswith other groups to accelerate industry and clinical uptake. In particular BCPP will contributeto an integrated UK RMP value chain by actively developing linkages with other UK RMPhubs to engage their complementary expertise. Constructive contacts have already beenestablished with the Edinburgh-led proposal on Engineering and Exploiting the Niche and theNewcastle-led proposal on Immune Tolerance. BCPP will also work closely with regulatorsand envisages extensive interaction with the Cell Therapy Catapult, in particular aroundstandardisation of cell therapy products. Together this will accelerate progress to clinical trialsand foster industry engagement","abstract":"The Biomedical Cell Production Platform (BCPP) will establish, advance and standardise emerging pluripotent stem cell technologies so as to achieve a leading position in the field of stem cell product development for clinical trials.Limited availability of human donor tissue is a key issue in regenerative medicine. This problem is particularly pronounced in tissues with restricted regenerative potential such as the nervous system. However, advances in the fields of pluripotent stem cells (PSC) and cell programming provide unprecedented opportunities to generate safe donor cells for all human tissues and organs in virtually unlimited numbers. These advances include: (i) the availability of clinical grade human embryonic stem cells; (ii) the capability to reprogramme patient somatic cells into induced pluripotent stem cells (iPSC); (iii) protocols for differentiating or forward programming PSC into therapeutically relevant somatic cell types; (iv) technologies for directly converting tissue-specific cells into other somatic cell fates;(v) methods forgenetic modification without collateral damage of the donor cell genome; vi) tools for identifying and monitoring genetic and epigenetic changes that may have significant consequences for safety and functional efficacy of PSC and their derivatives.Harnessingthese advances will enable an array of novel cell-mediated therapies. A prerequisite for the realisation of such therapeutic ambitions is a translational structure that melds fundamental discoveries into a pipeline for medical products and applications.BCPP will concentrate in-house activities on PSC and derivative tissue stem cell intermediates. However, the field in general will also benefit from tackling key knowledge gaps including: (i) establishment of standardised systems for the generation of robust genetically stable human PSC populations suitable for therapeutic translation,(ii)development and implementation of genetic modification tools that bypass the risk of insertional mutagenesis and are subject to science-based risk assessment, (iii) development of effective, reliable and reproducible differentiation protocols yielding functional and clinically compliant tissue-specific donor cells, (iv) quality control systems suitable for consistent manufacturing of stem cells and differentiated progeny suitable for use in human applications.BCPP will implement a translational research programme to reach the followinggoals:Tools for monitoring and assessing the significance of genetic and epigenetic variation in PSCs.Qualified methods that minimise the occurrence of functionally significant variants of undifferentiated ES and iPS cells and their differentiated derivatives during generation and expansion.Standardised, integration-free and clinically compliant technologies for iPS cell production and direct cell fate conversion.Technology for large-scale production from PSCs of standardised tissue-specific stem and progenitor cells suitable for preparation of cell-based medicines.Regulatory compliant procedures and best practice documents for producing safe pluripotent stem cell-derived somatic phenotypes suitable for clinical trials.Added ValueThe combination of WT/MRC Cambridge Stem Cell Institute (SCI), the Sheffield Centre for Stem Cell Biology (CSCB), Sanger Institute (WTSI), and Babraham Institute constitutes unmatched strength in the UK for development of enabling technologies in the field of PSC biology, reprogramming and differentiation. NIBSC-HPA (UK Stem Cell Bank;UKSCB)provides essential complementary input on qualification of cell-based protocols, quality standards and regulatory requirements. The BCPP will integrate this combined expertise into goal-oriented translational programmes and will also develop strategic partnerships with other groups to accelerate industry and clinical uptake. In particular BCPP will contribute to an integrated UK RMP value chain by actively developing linkages with other UK RMP hubs to engage their complementary expertise. Constructive contacts have already been established with the Edinburgh-led proposal on Engineering and Exploiting the Niche and the Newcastle-led proposal on Immune Tolerance. BCPP will also work closely with regulators and envisages extensive interaction with the Cell Therapy Catapult, in particular around standardisation of cell therapy products. Together this will accelerate progress to clinical trials and foster industry engagement.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000977","title":"The study aims to detect somatic mutations in small bowel cancer","description":"Using next generation sequencing this study has detected a number of novel and previously known somatic mutations in small bowel cancer. Both the tumour tissue and surrounding normal were sequenced.","abstract":"Using next generation sequencing this study has detected a number of novel and previously known somatic mutations in small bowel cancer. Both the tumour tissue and surrounding normal were sequenced.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000978","title":"Cancer_Cell_Line_Exome_Sequencing_","description":"Genomic characterisation of a large series of cancer cell lines.","abstract":"A panel of over 1000 cancer cell lines are being characterised in order to enhance their utility to the scientific community. The characterisation will consist of exome and RNA sequencing as well as copy number (Affymetrix SNP6.0 array) and chip based expression analysis (Affymetrix U219 array). All data will be made publically available and can be accessed via the COSMIC Cell Line database (http://cancer.sanger.ac.uk/cancergenome/projects/cell_lines/).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-09-19T12:52:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000979","title":"Pulldown_DNA_methylation_study_v2","description":"Pilot study to set up sequencing protocols for targeted pulldown methylation profiling","abstract":"This study is to set up protocols for targeted pulldown bisulfite-treatment DNA sequencing with small amount of input DNA.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-09-19T16:01:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000980","title":"Confirmation of a founder effect in a Northern European population (FRL) of a new beta-globin variant: HBB:c.23_26dup (codons 8/9 (+AGAA))","description":"Beta-thalassemia is a genetic disease caused by a defect in the production of the beta-like globin chain. More than 200 known different variants can lead to the disease and are mainly found in populations that have been exposed to malaria parasites. We recently described a duplication of 4 nucleotides in the first exon of beta-globin gene in several families of patients living in Nord-Pas-de-Calais (France). Using the genotypes at 12 microsatellite markers surrounding the beta-globin gene of four unrelated variant carriers plus an additional one recently discovered, we found that they shared a common haplotype indicating a founder effect that was estimated to have taken place 225 years ago (9 generations). In order to determine whether this variant arose in this region of Northern-Europe or was introduced by migrants from regions of the world where thalassemia is endemic, we genotyped the first 4 unrelated variant carriers and 32 controls from Nord-Pas-de-Calais for 97 European ancestry informative markers (EAIMs). Using these EAIMs and comparing with population reference panels, we demonstrated that the variant carriers were very similar to the controls and were closer to North European populations than to South European or Middle-East populations.  Rare beta-thalassemia variants have already been described in patients sampled in non-endemic regions but it is the first proof of a founder effect in Northern Europe.  The new genetic panel FRL is under registration in EGA.","abstract":"Beta-thalassemia is a genetic disease caused by a defect in the production of the beta-like globin chain. More than 200 known different variants can lead to the disease and are mainly found in populations that have been exposed to malaria parasites. We recently described a duplication of 4 nucleotides in the first exon of beta-globin gene in several families of patients living in Nord-Pas-de-Calais (France). Using the genotypes at 12 microsatellite markers surrounding the beta-globin gene of four unrelated variant carriers plus an additional one recently discovered, we found that they shared a common haplotype indicating a founder effect that was estimated to have taken place 225 years ago (9 generations). In order to determine whether this variant arose in this region of Northern-Europe or was introduced by migrants from regions of the world where thalassemia is endemic, we genotyped the first 4 unrelated variant carriers and 32 controls from Nord-Pas-de-Calais for 97 European ancestry informative markers (EAIMs). Using these EAIMs and comparing with population reference panels, we demonstrated that the variant carriers were very similar to the controls and were closer to North European populations than to South European or Middle-East populations.  Rare beta-thalassemia variants have already been described in patients sampled in non-endemic regions but it is the first proof of a founder effect in Northern Europe.  The new genetic panel FRL is under registration in EGA.","study_type":"Other","pubmed_ids":[25469539],"external_links":null,"is_released":true,"released_date":"2014-09-22T14:43:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000981","title":"We evaluate the PGD/PGS including 129 couples with NGS test and 266 couples with SNP-array test for the detection of embryonic chromosomal abnormalities.","description":"A total of 395 couples were subjected to IVF-PGD treatment, including 129 couples with NGS test and 266 couples with SNP-array test for the detection of embryonic chromosomal abnormalities. The NGS test was performed using low coverage whole genome sequencing with HiSeq 2000 platform. And the SNP array test was using Affymetrix Gene Chip Mapping Nsp I 262K.","abstract":"A total of 395 couples were subjected to IVF-PGD treatment, including 129 couples with NGS test and 266 couples with SNP-array test for the detection of embryonic chromosomal abnormalities. The NGS test was performed using low coverage whole genome sequencing with HiSeq 2000 platform. And the SNP array test was using Affymetrix Gene Chip Mapping Nsp I 262K.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-09-23T08:44:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000982","title":"Frequent alterations in cytoskeleton remodeling genes in primary and metastatic Chinese lung adenocarcinomas","description":"The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including themost commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scalesequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma.","abstract":"The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including themost commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scalesequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma.","study_type":"Other","pubmed_ids":[26647728],"external_links":null,"is_released":true,"released_date":"2014-09-24T02:26:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000983","title":"SOFT_study___sequencing_premenopausal_breast_cancer","description":"Our project will examine the role of PIK3CA mutations and their sensitivity to endocrine therapies and its role, with the addition of complete ovarian suppression. We plan to test our hypotheses using tumour samples collected from patients enrolled in the SOFT/IBCSG24-02 clinical study (Suppression of Ovarian Function Trial – (NCT00066690). SOFT is a phase III trial that randomised 3066 premenopausal women to evaluate if adding ovarian suppression to adjuvant endocrine therapy will improve clinical outcomes.","abstract":"Breast cancer arising in young women, particularly those less than 40 years at diagnosis, has long been observed to be associated with a poorer prognosis independent of clinic-pathological factors. The reasons for this remain unclear. We hypothesize that certain mutations or combinations are associated with endocrine-responsive BC diagnosed in young premenopausal women and these mutations will impact on survival outcomes. We also hypothesize that improved understanding of genomic profiles of ER+ BC diagnosed in young women will lead to better treatment decisions regarding their adjuvant hormonal and chemo-therapies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-09-24T14:43:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000984","title":"Suppresstem_FP7","description":"The EU Suppresstem project is a project aimed at identifying antibodies with anti-colon cancer characteristics. They are screened for this activity on colon cancer organoids of which the DNA sequence will be determined by the Sanger Institute.","abstract":"The EU Suppresstem project is a project aimed at identifying antibodies with anti-colon cancer characteristics. They are screened for this activity on colon cancer organoids of which the DNA sequence will be determined by the Sanger Institute.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000985","title":"_RNAseq___Colorectal_organoids_and_tumoroids","description":"Transcriptome sequencing of tumour tissue, adjacent normal tissue and derived organoids/tumoroids from colorectal cancer","abstract":"This study aims to describe expression heterogeneity within colorectal tumour tissue, and tumour-derived organoids.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-09-24T15:17:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000986","title":"Yeast_KO_Seq_Strategy_1__Mutational_signatures_of_DNA_damage_and_repair_processes","description":"Mutational signatures attributable to all viable S.cerevisiae gene knockouts (approx. 4000) will be determined. 8 independent samples from each knockout will be grown with a single cell cloning bottleneck. These will then be sequenced 96 samples per lane (12 strains/8 colonies per strain).","abstract":"This work is part of the broader WTSA investigating mutational signatures of DNA damage and repair processes.Mutational signatures attributable to all viable S.cerevisiae will be determined.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000987","title":"Yeast_KO_Seq_Strategy_2__Mutational_signatures_of_DNA_damage_and_repair_processes","description":"Mutational signatures attributable to all viable S.cerevisiae gene knockouts (approx. 4000) will be determined. 8 independent samples from each knockout will be grown but with no late stage single cell cloning to be performed. The 8 samples will then be pooled at the end of the study, with WGS performed to higher coverage on the resulting pooled sample.","abstract":"This work is part of the broader WTSA investigating mutational signatures of DNA damage and repair processes.Mutational signatures attributable to all viable S.cerevisiae will be determined.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000988","title":"30X_WGS_sequencing_of_100_individuals_from_the_general_Greek_population","description":"This project entailed generation of high depth WGS (30x) of 100 individuals from the general Greek population.","abstract":"This project entailed generation of high depth WGS (30x) of 100 individuals from the general Greek population.","study_type":"Other","pubmed_ids":[23347264,23399026],"external_links":null,"is_released":true,"released_date":"2014-09-26T06:58:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000989","title":"Sequence depth determination","description":"13 deeply sequenced exomes, used to apply a subset-based approach in order to determine the minimal required sequencing depth.","abstract":"13 deeply sequenced exomes, used to apply a subset-based approach in order to determine the minimal required sequencing depth.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000990","title":"Fetal hemoglobin in sickle cell disease patients from Tanzania","description":"Levels of fetal hemoglobin have been associated with differences in severity and outcome of sickle cell disease (SCD). While some genetic associations have been reported between SNPs and HbF level, little of the variance in the trait is explained, and most studies have focused on African American, rather than African samples. We have carried out a GWAS in a collection of SCD patients from Dar es Salaam, Tanzania. This sample represents a diverse, metropolitan collection of individuals from East Africa. Omni 2.5M genotypes and HbF levels (measured after 5 years of age) are available.","abstract":"Levels of fetal hemoglobin have been associated with differences in severity and outcome of sickle cell disease (SCD). While some genetic associations have been reported between SNPs and HbF level, little of the variance in the trait is explained, and most studies have focused on African American, rather than African samples. We have carried out a GWAS in a collection of SCD patients from Dar es Salaam, Tanzania. This sample represents a diverse, metropolitan collection of individuals from East Africa. Omni 2.5M genotypes and HbF levels (measured after 5 years of age) are available.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-09-26T15:48:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000991","title":"Therapeutic Resistance to PI3K-alpha Inhibitors","description":"We have studied the tumor genomic evolution in a patient with metastatic breast cancer bearing an activating PIK3CA mutation. The patient was treated with the PI3Kα inhibitor BYL719 and achieved a lasting clinical response on BYL719, but eventually progressed to treatment and died shortly thereafter. A rapid autopsy was performed and a total of 14 metastatic lesions were collected for further analysis. In order to identify possible genetic determinants of acquired resistance to PI3Kα inhibition, we took a three-step approach. First, we examined both the primary tumor (before BYL719 treatment) and the new lung metastasis by whole genome sequencing (DNA from the spleen was used as a normal control). Then, we analyzed the primary tumor, lung metastasis, and the peri-aortic lesion that remained stable (responding) at the time of progression to BYL719 therapy by whole exome sequencing. Finally, to confirm and expand our findings, we sequenced the primary tumor and all the metastatic lesions to &gt;500-fold coverage using a custom targeted deep-sequencing assay, MSK-IMPACT. Using this 3-step approach, we have demonstrated that patient’s lesion underwent parallel genetic evolution at multiple metastatic sites with different PTEN genomic alterations leading to a convergent PTEN- null phenotype resistant to PI3Kα inhibition. In order to expand our observations, we analyzed paired samples (pre-treatment and at progression) from six additional patients enrolled in the BYL719 trial. Acquired bi-allelic loss of PTEN was found in one additional patient treated with BYL719 whereas in two patients PIK3CA mutations present in the primary tumor were no longer detected at the time of progression. To functionally characterize our findings, inducible PTEN knockdown in sensitive cells resulted in resistance to BYL719, while simultaneous PI3K-p110β blockade reverted this resistance phenotype, both in cell lines and in PTEN-null xenografts derived from our patient. We conclude that parallel genetic evolution of separate sites with different PTEN genomic alterations leads to a convergent PTEN-null phenotype resistant to PI3Kα inhibition.","abstract":"We have studied the tumor genomic evolution in a patient with metastatic breast cancer bearing an activating PIK3CA mutation. The patient was treated with the PI3Kα inhibitor BYL719 and achieved a lasting clinical response on BYL719, but eventually progressed to treatment and died shortly thereafter. A rapid autopsy was performed and a total of 14 metastatic lesions were collected for further analysis. In order to identify possible genetic determinants of acquired resistance to PI3Kα inhibition, we took a three-step approach. First, we examined both the primary tumor (before BYL719 treatment) and the new lung metastasis by whole genome sequencing (DNA from the spleen was used as a normal control). Then, we analyzed the primary tumor, lung metastasis, and the peri-aortic lesion that remained stable (responding) at the time of progression to BYL719 therapy by whole exome sequencing. Finally, to confirm and expand our findings, we sequenced the primary tumor and all the metastatic lesions to &gt;500-fold coverage using a custom targeted deep-sequencing assay, MSK-IMPACT. Using this 3-step approach, we have demonstrated that patient’s lesion underwent parallel genetic evolution at multiple metastatic sites with different PTEN genomic alterations leading to a convergent PTEN- null phenotype resistant to PI3Kα inhibition. In order to expand our observations, we analyzed paired samples (pre-treatment and at progression) from six additional patients enrolled in the BYL719 trial. Acquired bi-allelic loss of PTEN was found in one additional patient treated with BYL719 whereas in two patients PIK3CA mutations present in the primary tumor were no longer detected at the time of progression. To functionally characterize our findings, inducible PTEN knockdown in sensitive cells resulted in resistance to BYL719, while simultaneous PI3K-p110β blockade reverted this resistance phenotype, both in cell lines and in PTEN-null xenografts derived from our patient. We conclude that parallel genetic evolution of separate sites with different PTEN genomic alterations leads to a convergent PTEN-null phenotype resistant to PI3Kα inhibition.","study_type":"Other","pubmed_ids":[25409150],"external_links":null,"is_released":true,"released_date":"2014-09-26T18:48:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000992","title":"Human melanoma samples with and without resistance to BRAF inhibitor therapy","description":"Human melanoma samples were collected pre, on, and progression on BRAF inhibitor therapy. RNA was extracted and run on RNA-seq. This has provided insights into different categories of BRAF inhibitor resistance mechanisms.","abstract":"Human melanoma samples were collected pre, on, and progression on BRAF inhibitor therapy. RNA was extracted and run on RNA-seq. This has provided insights into different categories of BRAF inhibitor resistance mechanisms.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-09-26T21:26:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000993","title":"Identification of causal mutation in two patients with Sotos Syndrome Features","description":"We performed whole exome sequencing (WES) on genomic DNA derived from two patients with Sotos Syndrome Features. Sequencing (100 base pair paired-end) was performed on an Illumina Hiseq 2000 sequencer after enrichment of 62Mb of exonic and adjacent intronic sequences with TruSeq Exome Enrichment Kit (Illumina, San Diego, CA, USA).","abstract":"We performed whole exome sequencing (WES) on genomic DNA derived from two patients with Sotos Syndrome Features. Sequencing (100 base pair paired-end) was performed on an Illumina Hiseq 2000 sequencer after enrichment of 62Mb of exonic and adjacent intronic sequences with TruSeq Exome Enrichment Kit (Illumina, San Diego, CA, USA).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-09-29T19:26:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000994","title":"Yeast_DNA_polymerase_point_mutants__Mutational_signatures_of_DNA_damage_and_repair_processes","description":"Mutational signatures attributable to DNA polymerase point mutations will be determined. Mutant strains went through single-cell bottlenecks and either 2 or 18 independent propagation lines per strain were generated. 2 independent colonies per line and controls will be sequenced; 96 samples per lane.","abstract":"This work is part of the broader WTSA investigating mutational signatures of DNA damage and repair processes.Mutational signatures attributable to DNA polymerase point mutations will be determined.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000995","title":"McGill Epigenomics Mapping Centre","description":"The McGill Epigenomics Mapping Centre (EMC) and Data Coordination Centre (EDCC) were established in 2012 at the McGill University and Genome Quebec Innovation Centre (Montreal, Canada) to support large-scale human epigenome mapping for a broad spectrum of cell types and diseases. Previous epigenetic studies have provided profiles of specific chromatin marks in relation to basic biological processes, and future studies of molecular mechanisms must build upon these proofs-of-concept by integrating sequence-based variation with multiple levels of epigenetic and transcriptional regulation across the genome of human tissues and animal disease models. This project leverages the high-throughput sequencing infrastructure and expertise in genomics and transcriptomics at the McGill Innovation Centre to carry out this research. Controlled access to the data by collaborators and the greater scientific community is gained via a portal, which takes advantage of Compute Canada high-performance computing cluster resources to manage the large volume of data associated from the generation of reference epigenome maps.            McGill University is one of two Canadian mapping and data coordination centres, the other based at the Michael Smith Genome Sciences Centre in Vancouver, British Columbia. The generation of comprehensive epigenome maps at McGill University is part of a larger international effort that is coordinated by the International Human Epigenome Consortium (IHEC), whose overall long-term objective is to determine the extent to which the epigenome shapes human populations over generations and in response to the environment.            This project is funded under the Canadian Epigenetics, Environment, and Health Research Consortium (CEEHRC) by the Canadian Institutes of Health Research and by Genome Quebec, with additional support from Genome Canada. The computing and networking infrastructure, and part of the software development, are provided by Compute Canada and CANARIE.","abstract":"The McGill Epigenomics Mapping Centre (EMC) and Data Coordination Centre (EDCC) were established in 2012 at the McGill University and Genome Quebec Innovation Centre (Montreal, Canada) to support large-scale human epigenome mapping for a broad spectrum of cell types and diseases. Previous epigenetic studies have provided profiles of specific chromatin marks in relation to basic biological processes, and future studies of molecular mechanisms must build upon these proofs-of-concept by integrating sequence-based variation with multiple levels of epigenetic and transcriptional regulation across the genome of human tissues and animal disease models. This project leverages the high-throughput sequencing infrastructure and expertise in genomics and transcriptomics at the McGill Innovation Centre to carry out this research. Controlled access to the data by collaborators and the greater scientific community is gained via a portal, which takes advantage of Compute Canada high-performance computing cluster resources to manage the large volume of data associated from the generation of reference epigenome maps.            McGill University is one of two Canadian mapping and data coordination centres, the other based at the Michael Smith Genome Sciences Centre in Vancouver, British Columbia. The generation of comprehensive epigenome maps at McGill University is part of a larger international effort that is coordinated by the International Human Epigenome Consortium (IHEC), whose overall long-term objective is to determine the extent to which the epigenome shapes human populations over generations and in response to the environment.            This project is funded under the Canadian Epigenetics, Environment, and Health Research Consortium (CEEHRC) by the Canadian Institutes of Health Research and by Genome Quebec, with additional support from Genome Canada. The computing and networking infrastructure, and part of the software development, are provided by Compute Canada and CANARIE.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-10-01T17:12:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000996","title":"Illumina HumanOmniExpress genotyping data from the TEENAGE (TEENs of Attica: Genes and Environment) study.","description":"The TEENAGE study is a cross-sectional study comprising healthy Greek adolescents. The study was conducted according to the guidelines specified in the Declaration of Helsinki and all procedures involving human subjects were approved by the Institutional Review Board of Harokopio University and the Greek Ministry of Education, Lifelong Learning and Religious Affairs. The TEENAGE study target population comprised adolescent students aged 13 to 15 years attending the first three classes of public secondary schools located in the wider Athens area of Attica. The regions across Attica from which students were recruited were physically similar and all urban in nature. Sampling of regions and schools selected to participate was random. Students were enrolled from the wider urban region to ensure that they were coming from families with varying educational background and socio-economic status. Moreover, in order to exclude any vast economic disparities, all participating schools were exclusively public schools, which are free of charge. A total of twenty-four schools participated in the study out of 285 junior secondary public schools in Attica. Anthropometric, medical and dietary information was obtained. DNA samples were genotyped using Illumina HumanOmniExpress BeadChips (Illumina, San Diego, CA, USA) at the Wellcome Trust Sanger Institute, Hinxton, UK. Genotype calling algorithm used was Illuminus (Teo et al., 2007).","abstract":"The TEENAGE study is a cross-sectional study comprising healthy Greek adolescents. The study was conducted according to the guidelines specified in the Declaration of Helsinki and all procedures involving human subjects were approved by the Institutional Review Board of Harokopio University and the Greek Ministry of Education, Lifelong Learning and Religious Affairs. The TEENAGE study target population comprised adolescent students aged 13 to 15 years attending the first three classes of public secondary schools located in the wider Athens area of Attica. The regions across Attica from which students were recruited were physically similar and all urban in nature. Sampling of regions and schools selected to participate was random. Students were enrolled from the wider urban region to ensure that they were coming from families with varying educational background and socio-economic status. Moreover, in order to exclude any vast economic disparities, all participating schools were exclusively public schools, which are free of charge. A total of twenty-four schools participated in the study out of 285 junior secondary public schools in Attica. Anthropometric, medical and dietary information was obtained. DNA samples were genotyped using Illumina HumanOmniExpress BeadChips (Illumina, San Diego, CA, USA) at the Wellcome Trust Sanger Institute, Hinxton, UK. Genotype calling algorithm used was Illuminus (Teo et al., 2007).","study_type":"Other","pubmed_ids":[23347264,23399026],"external_links":null,"is_released":true,"released_date":"2014-10-03T14:45:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001000997","title":"Predicting hair colour phenotype from genotype","description":"There are multiple polymorphisms across the pigmentary genes that through complex interactions constitute hair colour of an individual. For many years both in the anthropological and forensic field hair colour prediction from DNA has been a subjects of a number of publications. Here we present a prediction tool in a form of a mathematical model incorporating genotype of selected single nucleotide polymorphisms (SNPs) to determine hair colour. 22 SNPs within genes involved in human pigmentation were genotyped in a group of 186 Polish subjects representing different shades of hair colour. Based on the results genotype-phenotype association analysis was performed and multinomial logistic regression model for hair colour prediction from a set of SNPs was created. We identified seven variants highly associated with different hair colour categories. The obtained model utilized 11 genetic variants to categorize hair colour of an individual into one of the three established categories: red, blond and dark. Validation of our model showed good prediction accuracies expressed as area under the curve (AUC) of the receiver operating characteristic, this is AUC of 0.87 for the red haired, 0.84 for the dark haired and 0.77 for blond haired; this results are comparable with the parameters of other prediction models published in the recent years. Our model utilizes small number of genetic variants, allows for a reasonably accurate identification of hair colour and incorporates additional informative polymorphisms used for the first time as markers in a hair colour prediction model.","abstract":"There are multiple polymorphisms across the pigmentary genes that through complex interactions constitute hair colour of an individual. For many years both in the anthropological and forensic field hair colour prediction from DNA has been a subjects of a number of publications. Here we present a prediction tool in a form of a mathematical model incorporating genotype of selected single nucleotide polymorphisms (SNPs) to determine hair colour. 22 SNPs within genes involved in human pigmentation were genotyped in a group of 186 Polish subjects representing different shades of hair colour. Based on the results genotype-phenotype association analysis was performed and multinomial logistic regression model for hair colour prediction from a set of SNPs was created. We identified seven variants highly associated with different hair colour categories. The obtained model utilized 11 genetic variants to categorize hair colour of an individual into one of the three established categories: red, blond and dark. Validation of our model showed good prediction accuracies expressed as area under the curve (AUC) of the receiver operating characteristic, this is AUC of 0.87 for the red haired, 0.84 for the dark haired and 0.77 for blond haired; this results are comparable with the parameters of other prediction models published in the recent years. Our model utilizes small number of genetic variants, allows for a reasonably accurate identification of hair colour and incorporates additional informative polymorphisms used for the first time as markers in a hair colour prediction model.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000998","title":"C1_chip_evaluation","description":"Study of technical variation across Fluidigm C1 chips","abstract":"Study of technical variation across Fluidigm C1 chips. Diluted RNA and ERCC spike ins run into C1 chips, libraries made and sequenced. All should be equal!","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001000999","title":"RCOR1 short description","description":"RCOR1 abstract","abstract":"RCOR1 abstract","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001000","title":"An RCOR1 loss-associated gene expression signature identifies a prognostically significant DLBCL subgroup","description":"Effective treatment of diffuse large B cell lymphoma (DLBCL) is plagued by heterogeneous responses to standard therapy, and molecular mechanisms underlying unfavorable outcomes in lymphoma patients remain elusive. Here, we profiled 148 genomes with 91 matching transcriptomes in an R-CHOP-treated DLBCL cohort to uncover molecular subgroups linked to treatment failure. Systematic integration of high-resolution genotyping arrays and RNA-seq data revealed novel deletions in RCOR1 to be associated with unfavorable progression free survival (P = 0.001). Integration of expression data from the clinical samples with data from RCOR1 knockdowns in the lymphoma cell lines KM-H2 and Raji yielded an RCOR1 loss-associated gene signature comprising of 233 genes. This signature identified a subgroup of patients with unfavorable overall survival (OS) (P = 0.023). The prognostic significance of the 233-gene signature for OS was reproduced in an independent cohort comprising of 195 R- CHOP treated patients (P = 0.039). Additionally, we discovered that within the IPI low risk group, the gene signature provides additional prognostic value that was independent of the cell-of-origin phenotype. Taken together, we present a novel and reproducible molecular subgroup of DLBCL, impacting risk-stratification of R- CHOP treated DLBCL patients and revealing a new avenue for therapeutic intervention strategies.","abstract":"Effective treatment of diffuse large B cell lymphoma (DLBCL) is plagued by heterogeneous responses to standard therapy, and molecular mechanisms underlying unfavorable outcomes in lymphoma patients remain elusive. Here, we profiled 148 genomes with 91 matching transcriptomes in an R-CHOP-treated DLBCL cohort to uncover molecular subgroups linked to treatment failure. Systematic integration of high-resolution genotyping arrays and RNA-seq data revealed novel deletions in RCOR1 to be associated with unfavorable progression free survival (P = 0.001). Integration of expression data from the clinical samples with data from RCOR1 knockdowns in the lymphoma cell lines KM-H2 and Raji yielded an RCOR1 loss-associated gene signature comprising of 233 genes. This signature identified a subgroup of patients with unfavorable overall survival (OS) (P = 0.023). The prognostic significance of the 233-gene signature for OS was reproduced in an independent cohort comprising of 195 R- CHOP treated patients (P = 0.039). Additionally, we discovered that within the IPI low risk group, the gene signature provides additional prognostic value that was independent of the cell-of-origin phenotype. Taken together, we present a novel and reproducible molecular subgroup of DLBCL, impacting risk-stratification of R- CHOP treated DLBCL patients and revealing a new avenue for therapeutic intervention strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-10-08T22:13:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001001","title":"Illumina HumanCoreExome genotyping data from the TEENAGE (TEENs of Attica: Genes and Environment) study.","description":"The TEENAGE study is a cross-sectional study comprising healthy Greek adolescents. The study was conducted according to the guidelines specified in the Declaration of Helsinki and all procedures involving human subjects were approved by the Institutional Review Board of Harokopio University and the Greek Ministry of Education, Lifelong Learning and Religious Affairs. The TEENAGE study target population comprised adolescent students aged 13 to 15 years attending the first three classes of public secondary schools located in the wider Athens area of Attica. The regions across Attica from which students were recruited were physically similar and all urban in nature. Sampling of regions and schools selected to participate was random. Students were enrolled from the wider urban region to ensure that they were coming from families with varying educational background and socio-economic status. Moreover, in order to exclude any vast economic disparities, all participating schools were exclusively public schools, which are free of charge. A total of twenty-four schools participated in the study out of 285 junior secondary public schools in Attica. Anthropometric, medical and dietary information was obtained. DNA samples were genotyped using Illumina HumanCoreExome BeadChips (Illumina, San Diego, CA, USA) at the Wellcome Trust Sanger Institute, Hinxton, UK. Genotypes were called using GenCall (Illumina Genome Studio) followed by zCall and quality control (QC) was performed in two stages (pre- and post-zCall).","abstract":"The TEENAGE study is a cross-sectional study comprising healthy Greek adolescents. The study was conducted according to the guidelines specified in the Declaration of Helsinki and all procedures involving human subjects were approved by the Institutional Review Board of Harokopio University and the Greek Ministry of Education, Lifelong Learning and Religious Affairs. The TEENAGE study target population comprised adolescent students aged 13 to 15 years attending the first three classes of public secondary schools located in the wider Athens area of Attica. The regions across Attica from which students were recruited were physically similar and all urban in nature. Sampling of regions and schools selected to participate was random. Students were enrolled from the wider urban region to ensure that they were coming from families with varying educational background and socio-economic status. Moreover, in order to exclude any vast economic disparities, all participating schools were exclusively public schools, which are free of charge. A total of twenty-four schools participated in the study out of 285 junior secondary public schools in Attica. Anthropometric, medical and dietary information was obtained. DNA samples were genotyped using Illumina HumanCoreExome BeadChips (Illumina, San Diego, CA, USA) at the Wellcome Trust Sanger Institute, Hinxton, UK. Genotypes were called using GenCall (Illumina Genome Studio) followed by zCall and quality control (QC) was performed in two stages (pre- and post-zCall).","study_type":"Other","pubmed_ids":[23347264,23399026],"external_links":null,"is_released":true,"released_date":"2014-10-09T13:05:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001002","title":"Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets","description":"Genomic analyses promise to improve tumor characterization in order to optimize personalized treatment for patients with hepatocellular carcinoma (HCC). Exome sequencing analysis of 243 liver tumors revealed mutational signatures associated with specific risk factors, mainly combined alcohol/tobacco consumption, aflatoxin B1 and HBV infection. We identified 161 putative driver genes associated with 11 recurrent pathways. Associations of mutations defined 3 groups of genes related to risk factors and centered on CTNNB1 (alcohol), TP53 (HBV) and AXIN1. Analyses according to tumor stage progression revealed TERT promoter mutation as an early event whereas FGF/CCND1 amplification, TP53 and CDKN2A alterations appeared at more advanced stages in aggressive tumors. In 24% of the tumors, we identified genetic alterations potentially targetable by FDA-approved drugs. In conclusion, we identified risk factor–specific mutational signatures and defined the extensive landscape of altered genes and pathways in HCC, which will be useful to design clinical trials for targeted therapy.","abstract":"Genomic analyses promise to improve tumor characterization in order to optimize personalized treatment for patients with hepatocellular carcinoma (HCC). Exome sequencing analysis of 243 liver tumors revealed mutational signatures associated with specific risk factors, mainly combined alcohol/tobacco consumption, aflatoxin B1 and HBV infection. We identified 161 putative driver genes associated with 11 recurrent pathways. Associations of mutations defined 3 groups of genes related to risk factors and centered on CTNNB1 (alcohol), TP53 (HBV) and AXIN1. Analyses according to tumor stage progression revealed TERT promoter mutation as an early event whereas FGF/CCND1 amplification, TP53 and CDKN2A alterations appeared at more advanced stages in aggressive tumors. In 24% of the tumors, we identified genetic alterations potentially targetable by FDA-approved drugs. In conclusion, we identified risk factor–specific mutational signatures and defined the extensive landscape of altered genes and pathways in HCC, which will be useful to design clinical trials for targeted therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-10-09T14:17:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001003","title":"An efficient and comprehensive strategy for genetic diagnostics of polycystic kidney disease","description":"We established and validated sequence capture based NGS testing approach for all genes known for cystic and polycystic kidney disease including PKD1. This setup overcomes the complication of unspecific capture of pseudogenes by applying a mapping algorithm efficiently and specifically aligning reads to the PKD1 locus.","abstract":"We established and validated sequence capture based NGS testing approach for all genes known for cystic and polycystic kidney disease including PKD1. This setup overcomes the complication of unspecific capture of pseudogenes by applying a mapping algorithm efficiently and specifically aligning reads to the PKD1 locus.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-10-09T16:09:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001004","title":"First genome-wide association study in an Australian Aboriginal population provides insights into genetic risk factors for Body Mass Index and Type 2 Diabetes","description":"A body mass index (BMI) &gt;22kg/m2 is a risk factor for type 2 diabetes (T2D) in Aboriginal Australians.  To identify loci associated with BMI and T2D we undertook a genome-wide association study using 1,355,133 quality-controlled single nucleotide polymorphisms (SNPs) genotyped (Illumina 2.5M Duo Beadchip) in 402 individuals in extended pedigrees from a Western Australian Aboriginal community.  Imputation using the thousand genomes (1000G) reference panel extended the analysis to 6,724,284 post quality-control autosomal SNPs.  No associations achieved genome-wide significance, commonly accepted as P&lt;5x10-8.  Nevertheless, genes/pathways in common with other ethnicities were identified despite the arrival of Aboriginal people in Australia &gt;45,000 years ago.  The top hit (rs10868204 Pgenotyped=1.50x10-6; rs11140653 Pimputed_1000G=2.90x10-7) for BMI lies 5’ of NTRK2, the type 2 neurotrophic tyrosine kinase receptor for brain-derived neurotrophic factor (BDNF) that regulates energy balance downstream of melanocortin-4 receptor (MC4R).  PIK3C2G (rs12816270 Pgenotyped=8.06x10-6; rs10841048 Pimputed_1000G=6.28x10-7) was associated with BMI, but not with T2D as reported elsewhere.  BMI also associated with CNTNAP2 (rs6960319 Pgenotyped=4.65x10-5; rs13225016 Pimputed_1000G=6.57x10-5), previously identified as the strongest gene-by-environment interaction for BMI in African-Americans.   The top hit (rs11240074 Pgenotyped=5.59x10-6, Pimputed_1000G=5.73x10-6) for T2D lies 5’ of BCL9 that, along with TCFL2, promotes beta-catenin’s transcriptional activity in the WNT signaling pathway.  Additional hits occurred in genes affecting pancreatic (KCNJ6, KCNA1) and/or GABA (GABRR1, KCNA1) functions.  Notable associations observed for genes previously identified at genome-wide significance in other populations included MC4R (Pgenotyped=4.49x10-4) for BMI and IGF2BP2 Pimputed_1000G=2.55x10-6) for T2D.  Our results may provide novel functional leads in understanding disease pathogenesis in this Australian Aboriginal population.","abstract":"A body mass index (BMI) &gt;22kg/m2 is a risk factor for type 2 diabetes (T2D) in Aboriginal Australians.  To identify loci associated with BMI and T2D we undertook a genome-wide association study using 1,355,133 quality-controlled single nucleotide polymorphisms (SNPs) genotyped (Illumina 2.5M Duo Beadchip) in 402 individuals in extended pedigrees from a Western Australian Aboriginal community.  Imputation using the thousand genomes (1000G) reference panel extended the analysis to 6,724,284 post quality-control autosomal SNPs.  No associations achieved genome-wide significance, commonly accepted as P&lt;5x10-8.  Nevertheless, genes/pathways in common with other ethnicities were identified despite the arrival of Aboriginal people in Australia &gt;45,000 years ago.  The top hit (rs10868204 Pgenotyped=1.50x10-6; rs11140653 Pimputed_1000G=2.90x10-7) for BMI lies 5’ of NTRK2, the type 2 neurotrophic tyrosine kinase receptor for brain-derived neurotrophic factor (BDNF) that regulates energy balance downstream of melanocortin-4 receptor (MC4R).  PIK3C2G (rs12816270 Pgenotyped=8.06x10-6; rs10841048 Pimputed_1000G=6.28x10-7) was associated with BMI, but not with T2D as reported elsewhere.  BMI also associated with CNTNAP2 (rs6960319 Pgenotyped=4.65x10-5; rs13225016 Pimputed_1000G=6.57x10-5), previously identified as the strongest gene-by-environment interaction for BMI in African-Americans.   The top hit (rs11240074 Pgenotyped=5.59x10-6, Pimputed_1000G=5.73x10-6) for T2D lies 5’ of BCL9 that, along with TCFL2, promotes beta-catenin’s transcriptional activity in the WNT signaling pathway.  Additional hits occurred in genes affecting pancreatic (KCNJ6, KCNA1) and/or GABA (GABRR1, KCNA1) functions.  Notable associations observed for genes previously identified at genome-wide significance in other populations included MC4R (Pgenotyped=4.49x10-4) for BMI and IGF2BP2 Pimputed_1000G=2.55x10-6) for T2D.  Our results may provide novel functional leads in understanding disease pathogenesis in this Australian Aboriginal population.","study_type":"Other","pubmed_ids":[25760438],"external_links":null,"is_released":true,"released_date":"2014-10-10T06:11:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001005","title":"Italian Network of Genetic Isolates - Carlantino village","description":"This project is focused on studying quantitative traits using the people of the Carlantino village a isolated population in southern Italy.","abstract":"This project is focused on studying quantitative traits using the people of the Carlantino village a isolated population in southern Italy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001006","title":"Italian Network of Genetic Isolates - Friuli Venezia Giulia Genetic Park","description":"This project is focused on studying quantitative traits using the people of the 6 isolated villages in the Friuli Venezia Giulia region of northern Italy: San Martino del Carso, Illegio, Erto-Casso, Sauris, Resia and Clauzetto.","abstract":"This project is focused on studying quantitative traits using the people of the 6 isolated villages in the Friuli Venezia Giulia region of northern Italy: San Martino del Carso, Illegio, Erto-Casso, Sauris, Resia and Clauzetto.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001007","title":"Italian Network of Genetic Isolates - Val Borbera","description":"This project is focused on studying quantitative traits using the people living in the Val Borbera valley a isolated population in northern Italy.","abstract":"This project is focused on studying quantitative traits using the people living in the Val Borbera valley a isolated population in northern Italy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001008","title":"Silk Road Study","description":"This project is focused on studying sensory quantitative trais using the people from isolated populations located in 8 different countries/regions of central Asia: Arzebaijan, Georgia, Armenia, Kazakhstan, Crimea, Uzbekistan, Kirghizistan, Tajikistan.","abstract":"This project is focused on studying sensory quantitative trais using the people from isolated populations located in 8 different countries/regions of central Asia: Arzebaijan, Georgia, Armenia, Kazakhstan, Crimea, Uzbekistan, Kirghizistan, Tajikistan.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001009","title":"Biased allelic expression in human primary fibroblast single cells.","description":"The study of gene expression in mammalian single cells using genomic technologies now provides the possibility to investigate the patterns of allelic gene expression. We have used single-cell RNA sequencing to detect the allele-specific mRNA level in 203 single human primary fibroblast cells over 133,633 unique heterozygous single nucleotide variants (hetSNVs). We have observed that at the snapshot of analyses each cell contains mostly transcripts from one allele from the majority of genes; indeed 76.4% of the hetSNVs display stochastic monoallelic expression in single cells. Remarkably, adjacent hetSNVs exhibit haplotype consistent allelic ratio; in contrast distant sites located in two different genes are independent of the haplotype structure. Moreover, the allele-specific expression in single cells correlated with the abundance of the cellular transcript. We observed that genes expressing both alleles in majority of the single cells at a given time point are rare and enriched in highly expressed genes. The relative abundance of each allele in a cell is controlled by some regulatory mechanisms since we observed related single-cell allelic profiles according to genes. Overall, these results have direct implications in cellular phenotypic variability.","abstract":"The study of gene expression in mammalian single cells using genomic technologies now provides the possibility to investigate the patterns of allelic gene expression. We have used single-cell RNA sequencing to detect the allele-specific mRNA level in 203 single human primary fibroblast cells over 133,633 unique heterozygous single nucleotide variants (hetSNVs). We have observed that at the snapshot of analyses each cell contains mostly transcripts from one allele from the majority of genes; indeed 76.4% of the hetSNVs display stochastic monoallelic expression in single cells. Remarkably, adjacent hetSNVs exhibit haplotype consistent allelic ratio; in contrast distant sites located in two different genes are independent of the haplotype structure. Moreover, the allele-specific expression in single cells correlated with the abundance of the cellular transcript. We observed that genes expressing both alleles in majority of the single cells at a given time point are rare and enriched in highly expressed genes. The relative abundance of each allele in a cell is controlled by some regulatory mechanisms since we observed related single-cell allelic profiles according to genes. Overall, these results have direct implications in cellular phenotypic variability.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-10-14T13:55:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001010","title":"Genetic_aberrations_in_gastrointestinal_stromal_tumours__GISTs__and_their_associations_with_patient_outcome","description":"The Purpose of this present study is to identify novel genetic alterations in GIST using second-generation DNA sequencing on the GIST tumour genome.We intend to sequence the GIST exome from a maximum of 358 patients who were treated in the Scandinavian Sarcoma Group (SSG) XVIII/Arbeitsgemeinschaft Internistische Onkologie (AIO) trial with either 12 or 36 months of adjuvant imatinib 400mg/day administered after surgery","abstract":"Gastrointestinal stromal tumour (GIST) is the most common sarcoma of the gastrointestinal tract. Most GISTs are driven by activating mutations in either KIT (75%) or PDGFRA (10%) genes, which are considered central in the tumour molecular pathogenesis and are therapeutic targets. Mutations in the succinate dehydrogenase (SDH) may occur in GIST that are wild-type with respect of KIT and PDGFRA, and rarely in BRAF. However, further gene mutations are likely to occur in GIST, and such mutations may have clinical relevance.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001011","title":"MDS Sequencing Project_Cancer Cell","description":"Myelodysplastic syndromes (MDS) are uncommon entities, heterogeneous clinically and cytogenetically. The aim of the present study is to determine genetic alteration in this subset of patients. Expected results: Identification of new aberrations and genetic markers in order to detect novel genes involved in MDS 5q-response to Lenalidomide's treatment.","abstract":"Myelodysplastic syndromes (MDS) are uncommon entities, heterogeneous clinically and cytogenetically. The aim of the present study is to determine genetic alteration in this subset of patients. Expected results: Identification of new aberrations and genetic markers in order to detect novel genes involved in MDS 5q-response to Lenalidomide's treatment.","study_type":"Other","pubmed_ids":[25242043],"external_links":null,"is_released":true,"released_date":"2014-10-17T15:04:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001012","title":"The NIHR BioResource Rare Diseases BRIDGE consortium sequencing projects","description":"The NIHR BioResource Rare Diseases BRIDGE consortium is a collaboration between 13 Rare Disease projects that aim to discover the genetic sequence variants underlying unresolved inherited disorders and to improve identification of already identified high penetrance variants. BRIDGE projects cover a variety of rare disease research areas including Cardiovascular, Infection and Immunity and Neuroscience. The consortium aims to sequence 8,000 samples across the different projects by 2017.","abstract":"The NIHR BioResource Rare Diseases BRIDGE consortium is a collaboration between 13 Rare Disease projects that aim to discover the genetic sequence variants underlying unresolved inherited disorders and to improve identification of already identified high penetrance variants. BRIDGE projects cover a variety of rare disease research areas including Cardiovascular, Infection and Immunity and Neuroscience. The consortium aims to sequence 8,000 samples across the different projects by 2017.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-10-20T10:18:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001013","title":"Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness","description":"In this work, using exome sequencing, we identified biallelic PNLPA6 mutations in patients with childhood blindness due to severe photoreceptor death and clinical features of Leber congenital amaurosis (LCA) and, interestingly, also of the rare Oliver McFarlane Syndrome","abstract":"In this work, using exome sequencing, we identified biallelic PNLPA6 mutations in patients with childhood blindness due to severe photoreceptor death and clinical features of Leber congenital amaurosis (LCA) and, interestingly, also of the rare Oliver McFarlane Syndrome","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-10-20T17:37:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001014","title":"Spatial heterogeneity in medulloblastoma","description":"Spatial heterogeneity of transcriptional and genetic markers between physically isolated biopsies of a single tumor poses major barriers to the identification of biomarkers and the development of targeted therapies that will be effective against the entire tumor. We analyzed the spatial heterogeneity of multiregional biopsies from 35 patients, using a combination of transcriptomic and genomic profiles. Medulloblastomas (MBs), but not high-grade gliomas (HGGs), demonstrated spatially homogeneous transcriptomes, which allowed for accurate subgrouping of tumors from a single biopsy. Conversely, somatic mutations that affect genes suitable for targeted therapeutics demonstrated high levels of spatial heterogeneity in MB, malignant glioma, and renal cell carcinoma (RCC). Actionable targets found in a single MB biopsy were seldom clonal across the entire tumor,which brings the efficacy of monotherapies against a single target into question. Clinical trials of targeted therapies for MB should first ensure the spatially ubiquitous nature of the target mutation.","abstract":"Spatial heterogeneity of transcriptional and genetic markers between physically isolated biopsies of a single tumor poses major barriers to the identification of biomarkers and the development of targeted therapies that will be effective against the entire tumor. We analyzed the spatial heterogeneity of multiregional biopsies from 35 patients, using a combination of transcriptomic and genomic profiles. Medulloblastomas (MBs), but not high-grade gliomas (HGGs), demonstrated spatially homogeneous transcriptomes, which allowed for accurate subgrouping of tumors from a single biopsy. Conversely, somatic mutations that affect genes suitable for targeted therapeutics demonstrated high levels of spatial heterogeneity in MB, malignant glioma, and renal cell carcinoma (RCC). Actionable targets found in a single MB biopsy were seldom clonal across the entire tumor,which brings the efficacy of monotherapies against a single target into question. Clinical trials of targeted therapies for MB should first ensure the spatially ubiquitous nature of the target mutation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-10-21T22:51:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001015","title":"Exomes of High-risk Prostate cancer","description":"DNA extracted from tumoral tissue of 39 patients was used for exome sequencing. As a comparison, DNA extracted from blood was used as a non-tumoral control. DNA was captured using the EZ SeqCap v3 exome kit from Roche and sequenced using an Illumina HiSeq instrument.","abstract":"DNA extracted from tumoral tissue of 39 patients was used for exome sequencing. As a comparison, DNA extracted from blood was used as a non-tumoral control. DNA was captured using the EZ SeqCap v3 exome kit from Roche and sequenced using an Illumina HiSeq instrument.","study_type":"Other","pubmed_ids":[27014907],"external_links":null,"is_released":true,"released_date":"2014-10-23T10:47:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001016","title":"A Cancer Cell-Line Titration Series for Evaluating Somatic Classification","description":"Accurate detection of somatic single nucleotide variants and small insertions and deletions from DNA sequencing experiments of tumour-normal pairs is a challenging task.  Tumour samples are often contaminated with normal cells confounding the available evidence for the somatic variants.  Furthermore, tumours are heterogeneous so sub-clonal variants are observed at reduced allele frequencies.  We present here a cell-line titration series dataset that can be used to evaluate somatic variant calling pipelines with the goal of reliably calling true somatic mutations at low allele frequencies. \nCell-line DNA was mixed with matched normal DNA at 8 different ratios to generate samples with known tumour cellularities, and exome sequenced on Illumina HiSeq to depths of >300x.  The data was processed with several different variant calling pipelines and verification experiments were performed to assay >1,500 somatic variant candidates using Ion Torrent PGM as an orthogonal technology.  By examining the variants called at varying cellularities and depths of coverage, we show that the best performing pipelines are able to maintain a high level of precision at any cellularity.  In addition, we estimate the number of true somatic variants undetected as cellularity and coverage decrease.  Our cell-line titration series dataset, along with the associated verification results, is effective for this evaluation and will serve as a valuable dataset for future somatic calling algorithm development.","abstract":"Accurate detection of somatic single nucleotide variants and small insertions and deletions from DNA sequencing experiments of tumour-normal pairs is a challenging task.  Tumour samples are often contaminated with normal cells confounding the available evidence for the somatic variants.  Furthermore, tumours are heterogeneous so sub-clonal variants are observed at reduced allele frequencies.  We present here a cell-line titration series dataset that can be used to evaluate somatic variant calling pipelines with the goal of reliably calling true somatic mutations at low allele frequencies. Cell-line DNA was mixed with matched normal DNA at 8 different ratios to generate samples with known tumour cellularities, and exome sequenced on Illumina HiSeq to depths of &gt;300x.  The data was processed with several different variant calling pipelines and verification experiments were performed to assay &gt;1,500 somatic variant candidates using Ion Torrent PGM as an orthogonal technology.  By examining the variants called at varying cellularities and depths of coverage, we show that the best performing pipelines are able to maintain a high level of precision at any cellularity.  In addition, we estimate the number of true somatic variants undetected as cellularity and coverage decrease.  Our cell-line titration series dataset, along with the associated verification results, is effective for this evaluation and will serve as a valuable dataset for future somatic calling algorithm development.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-10-23T20:54:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001017","title":"Follow_up_for_second_tier_signals_from_the_arcOGEN_GWAS","description":"The arcOGEN UK nationwide consortium has been funded by the arc to undertake a genome-wide association scan in osteoarthritis. GWA genotyping has been carried out at the Sanger on the illumina 610k array. This replication study was desinged to follow-up second-tier signals from the arcOGEN GWS in 25 SNPs (1Sequenom iPLEX) with p&lt;5x10^-6 on 6000 additional UK OA and control samples.  ","abstract":"The arcOGEN UK nationwide consortium has been funded by the arc to undertake a genome-wide association scan in osteoarthritis. GWA genotyping has been carried out at the Sanger on the illumina 610k array. This replication study was desinged to follow-up second-tier signals from the arcOGEN GWS in 25 SNPs (1Sequenom iPLEX) with p&lt;5x10^-6 on 6000 additional UK OA and control samples.  ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-10-27T16:11:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001018","title":"Whole-genome plasma sequencing reveals focal amplifications as a driving force in metastatic prostate cancer","description":"Genomic alterations in metastatic prostate cancer remain incompletely characterized. Here we analyze 493 prostate cancer cases from the TCGA database and perform whole-genome plasma sequencing on 95 plasma samples derived from 43 patients with metastatic prostate cancer. From these samples, we identify established driver aberrations in a cancer-related gene in nearly all cases (97.7%), including driver gene fusions (TMPRSS2:ERG), driver focal deletions (PTEN, RYBP, SHQ1), and driver amplifications (AR, MYC). In serial plasma analyses, we observe changes in focal amplifications in 40% of cases. The mean time interval between new amplifications was 26.4 weeks (range: 5-52 weeks), suggesting that they represent rapid adaptations to selection pressure. An increase in neuron-specific enolase is accompanied by clonal pattern changes in the tumor genome, most consistent with subclonal diversification of the tumor. Our findings suggest a high plasticity of prostate cancer genomes with newly occurring focal amplifications as a driving force in progression","abstract":"Genomic alterations in metastatic prostate cancer remain incompletely characterized. Here we analyze 493 prostate cancer cases from the TCGA database and perform whole-genome plasma sequencing on 95 plasma samples derived from 43 patients with metastatic prostate cancer. From these samples, we identify established driver aberrations in a cancer-related gene in nearly all cases (97.7%), including driver gene fusions (TMPRSS2:ERG), driver focal deletions (PTEN, RYBP, SHQ1), and driver amplifications (AR, MYC). In serial plasma analyses, we observe changes in focal amplifications in 40% of cases. The mean time interval between new amplifications was 26.4 weeks (range: 5-52 weeks), suggesting that they represent rapid adaptations to selection pressure. An increase in neuron-specific enolase is accompanied by clonal pattern changes in the tumor genome, most consistent with subclonal diversification of the tumor. Our findings suggest a high plasticity of prostate cancer genomes with newly occurring focal amplifications as a driving force in progression","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-10-29T07:57:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001019","title":"(h)MeDIP-Seq of high-risk prostate cancer","description":"Immunoprecipitation of methylated and hydroxymethylated DNA was performed on DNA isolated from tumoral and non-tumoral prostate tissue of patients with high-risk disease.  Samples were sequenced on the Illumina HiSeq as 50 bp single end.","abstract":"Immunoprecipitation of methylated and hydroxymethylated DNA was performed on DNA isolated from tumoral and non-tumoral prostate tissue of patients with high-risk disease.  Samples were sequenced on the Illumina HiSeq as 50 bp single end.","study_type":"Other","pubmed_ids":[27014907],"external_links":null,"is_released":true,"released_date":"2014-10-29T08:17:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001020","title":"Genome-wide prediction of human embryos","description":"BACKGROUND:\nPreimplantation genetic diagnosis (PGD) enables profiling of embryos for genetic disorders prior to implantation. The majority of PGD testing is restricted in the scope of variants assayed or by the availability of extended family members. While recent advances in single cell sequencing show promise, they remain limited by bias in DNA amplification and the rapid turnaround time (&lt;36 h) required for fresh embryo transfer. Here, we describe and validate a method for inferring the inherited whole genome sequence of an embryo for preimplantation genetic diagnosis (PGD).\nMETHODS:\nWe combine haplotype-resolved, parental genome sequencing with rapid embryo genotyping to predict the whole genome sequence of a day-5 human embryo in a couple at risk of transmitting alpha-thalassemia.\nRESULTS:\nInheritance was predicted at approximately 3 million paternally and/or maternally heterozygous sites with greater than 99% accuracy. Furthermore, we successfully phase and predict the transmission of an HBA1/HBA2 deletion from each parent.\nCONCLUSIONS:\nOur results suggest that preimplantation whole genome prediction may facilitate the comprehensive diagnosis of diseases with a known genetic basis in embryos.","abstract":"BACKGROUND:\nPreimplantation genetic diagnosis (PGD) enables profiling of embryos for genetic disorders prior to implantation. The majority of PGD testing is restricted in the scope of variants assayed or by the availability of extended family members. While recent advances in single cell sequencing show promise, they remain limited by bias in DNA amplification and the rapid turnaround time (&lt;36 h) required for fresh embryo transfer. Here, we describe and validate a method for inferring the inherited whole genome sequence of an embryo for preimplantation genetic diagnosis (PGD).\nMETHODS:\nWe combine haplotype-resolved, parental genome sequencing with rapid embryo genotyping to predict the whole genome sequence of a day-5 human embryo in a couple at risk of transmitting alpha-thalassemia.\nRESULTS:\nInheritance was predicted at approximately 3 million paternally and/or maternally heterozygous sites with greater than 99% accuracy. Furthermore, we successfully phase and predict the transmission of an HBA1/HBA2 deletion from each parent.\nCONCLUSIONS:\nOur results suggest that preimplantation whole genome prediction may facilitate the comprehensive diagnosis of diseases with a known genetic basis in embryos.","study_type":"Other","pubmed_ids":[26019723],"external_links":null,"is_released":true,"released_date":"2014-10-30T02:35:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001021","title":"Exome_sequencing_of_EBV_driven_lymphoma","description":"Exome sequencing of a case of lethal EBV-driven LPD","abstract":"EBV-driven B cell neoplasms occur in profoundly immunosuppressed patients. Very occasionally these tumours happen in normal people without previous evidence of immunosuppression. We want to sequence a case of lethal EBV-driven LPD as a pilot project for understanding the genomic basis of this disease.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-10-30T14:53:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001022","title":"Whole genome sequencing of ASD quartet families","description":"Autism spectrum disorder (ASD) is genetically heterogeneous with &gt;100 susceptibility genes known. We used whole-genome sequencing (WGS) of 85 quartet families (two parents and two ASD-affected siblings) to comprehensively examine mutation characteristics. Our results emphasize using WGS to maximize the detection of all classes of mutations potentially involved in autism, and to enable the interpretation of that data in confirmatory and predictive diagnosis in different individuals in a family.","abstract":"Autism spectrum disorder (ASD) is genetically heterogeneous with &gt;100 susceptibility genes known. We used whole-genome sequencing (WGS) of 85 quartet families (two parents and two ASD-affected siblings) to comprehensively examine mutation characteristics. Our results emphasize using WGS to maximize the detection of all classes of mutations potentially involved in autism, and to enable the interpretation of that data in confirmatory and predictive diagnosis in different individuals in a family.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001023","title":"Whole genome sequencing of ASD quartet families","description":"Autism spectrum disorder (ASD) is genetically heterogeneous with &gt;100 susceptibility genes known. We used whole-genome sequencing (WGS) of 85 quartet families (two parents and two ASD-affected siblings) to comprehensively examine mutation characteristics. Our results emphasize using WGS to maximize the detection of all classes of mutations potentially involved in autism, and to enable the interpretation of that data in confirmatory and predictive diagnosis in different individuals in a family.","abstract":"Autism spectrum disorder (ASD) is genetically heterogeneous with &gt;100 susceptibility genes known. We used whole-genome sequencing (WGS) of 85 quartet families (two parents and two ASD-affected siblings) to comprehensively examine mutation characteristics. Our results emphasize using WGS to maximize the detection of all classes of mutations potentially involved in autism, and to enable the interpretation of that data in confirmatory and predictive diagnosis in different individuals in a family.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-10-31T02:16:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001024","title":"Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients","description":"Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients","abstract":"Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-10-31T06:15:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001025","title":"Comprehensive miRNA Sequence Analysis Reveals Survival Differences in Diffuse Large B-cell Lymphoma Patients","description":"Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease, with 30-40% of patients failing to achieve complete responses to standard therapy. miRNAs are RNA molecules that attenuate expression of their mRNA targets. To characterize the DLBCL miRNome, we sequenced miRNAs from 92 DLBCL and 15 benign centroblast fresh frozen samples and from 140 DLBCL formalin-fixed, paraffin-embedded tissue (FFPET) samples for validation.","abstract":"Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease, with 30-40% of patients failing to achieve complete responses to standard therapy. miRNAs are RNA molecules that attenuate expression of their mRNA targets. To characterize the DLBCL miRNome, we sequenced miRNAs from 92 DLBCL and 15 benign centroblast fresh frozen samples and from 140 DLBCL formalin-fixed, paraffin-embedded tissue (FFPET) samples for validation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-10-31T18:33:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001026","title":"Prediction and quantification of splice events from RNA-seq data","description":"Analysis of splice variants from short read RNA-seq data remains a challenging problem. Here we present a novel method for the genome-guided prediction and quantification of splice events from RNA-seq data, which enables the analysis of unannotated and complex splice events. Splice junctions and exons are predicted from reads mapped to a reference genome and are assembled into a genome-wide splice graph. Splice events are identified recursively from the graph and are quantified locally based on reads extending across the start or end of each splice variant. We assess prediction accuracy based on simulated and real RNA-seq data, and illustrate how different read aligners (GSNAP, HISAT2, STAR, TopHat2) affect prediction results. We validate our approach for quantification based on simulated data, and compare local estimates of relative splice variant usage with those from other methods (MISO, Cufflinks) based on simulated and real RNA-seq data. In a proof-of-concept study of splice variants in 16 normal human tissues (Illumina Body Map 2.0) we identify 249 internal exons that belong to known genes but are not related to annotated exons. Using independent RNA samples from 14 matched normal human tissues, we validate 9/9 of these exons by RT-PCR and 216/249 by paired-end RNA-seq (2 x 250 bp). These results indicate that de novo prediction of splice variants remains beneficial even in well-studied systems. An implementation of our method is freely available as an R/Bioconductor package SGSeq.","abstract":"Analysis of splice variants from short read RNA-seq data remains a challenging problem. Here we present a novel method for the genome-guided prediction and quantification of splice events from RNA-seq data, which enables the analysis of unannotated and complex splice events. Splice junctions and exons are predicted from reads mapped to a reference genome and are assembled into a genome-wide splice graph. Splice events are identified recursively from the graph and are quantified locally based on reads extending across the start or end of each splice variant. We assess prediction accuracy based on simulated and real RNA-seq data, and illustrate how different read aligners (GSNAP, HISAT2, STAR, TopHat2) affect prediction results. We validate our approach for quantification based on simulated data, and compare local estimates of relative splice variant usage with those from other methods (MISO, Cufflinks) based on simulated and real RNA-seq data. In a proof-of-concept study of splice variants in 16 normal human tissues (Illumina Body Map 2.0) we identify 249 internal exons that belong to known genes but are not related to annotated exons. Using independent RNA samples from 14 matched normal human tissues, we validate 9/9 of these exons by RT-PCR and 216/249 by paired-end RNA-seq (2 x 250 bp). These results indicate that de novo prediction of splice variants remains beneficial even in well-studied systems. An implementation of our method is freely available as an R/Bioconductor package SGSeq.","study_type":"Other","pubmed_ids":[27218464],"external_links":null,"is_released":true,"released_date":"2014-10-31T21:35:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001027","title":"NTRK1 gene rearrangement and its clinicopathological implication in colon cancer","description":"We identified recurrent lamin A/C (LMNA)-neurotrophic tyrosine kinase, receptor, type 1 (NTRK1) and tropomyosin 3 (TPM3)-NTRK1 fusions in Korean patients with colon cancer (3 of 147, 2%) through next generation RNA sequencing (RNA-seq). NTRK1 fusion was a mutually exclusive colon cancer driver with 25.6-29.2% prevalence in Korean and Chinese patients, accompanied with significantly short 10-year overall survival time. NTRK1 fusion gene was warranted as a clinically relevant therapeutic target for colon cancer intervention.","abstract":"We identified recurrent lamin A/C (LMNA)-neurotrophic tyrosine kinase, receptor, type 1 (NTRK1) and tropomyosin 3 (TPM3)-NTRK1 fusions in Korean patients with colon cancer (3 of 147, 2%) through next generation RNA sequencing (RNA-seq). NTRK1 fusion was a mutually exclusive colon cancer driver with 25.6-29.2% prevalence in Korean and Chinese patients, accompanied with significantly short 10-year overall survival time. NTRK1 fusion gene was warranted as a clinically relevant therapeutic target for colon cancer intervention.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001028","title":"Genomic Alterations in Gingivo-buccal Cancer: ICGC-India Project_YR02","description":"As a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India. There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection.  Paired DNA samples – isolated from the tumour tissue and from the blood of fifty six patients – have been analyzed to catalog germline and somatic mutations. Association between each observed genomic alteration and exposure to environmental risk factors is being explored.Detailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from blood and tumour tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai. Exome capture and deep resequencing are being performed at the National Institute of Biomedical Genomics, Kalyani. We have analyzed the exomes of paired blood and tumour DNA samples using exome capture by Illumina TrueSeq Exome Enrichment kit followed by sequencing on Illumina HiSeq-2000. Each exome is being sequenced at a mean depth of 70x for Tumour  and 40x  for Blood. In addition, we have used Illumina Omni 2.5 SNP-chips to generate genotype data.","abstract":"As a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India. There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection.  Paired DNA samples – isolated from the tumour tissue and from the blood of fifty six patients – have been analyzed to catalog germline and somatic mutations. Association between each observed genomic alteration and exposure to environmental risk factors is being explored.Detailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from blood and tumour tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai. Exome capture and deep resequencing are being performed at the National Institute of Biomedical Genomics, Kalyani. We have analyzed the exomes of paired blood and tumour DNA samples using exome capture by Illumina TrueSeq Exome Enrichment kit followed by sequencing on Illumina HiSeq-2000. Each exome is being sequenced at a mean depth of 70x for Tumour  and 40x  for Blood. In addition, we have used Illumina Omni 2.5 SNP-chips to generate genotype data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-11-03T12:27:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001029","title":"Sequencing_of_RNA_samples_from_haematopoietic_cells","description":"As part of the Cardiogenics collaboration we have performed an e-QTL study in monocytes and macrophages in 425 health individuals of the Cambridge BioResource. To better define the transcript landscape of both cells we wish to sequence the RNA of monocytes, macrophages and other relevant haematopoietic cells/cell lines.","abstract":"As part of the Cardiogenics collaboration we have performed an e-QTL study in monocytes and macrophages in 425 health individuals of the Cambridge BioResource. To better define the transcript landscape of both cells we wish to sequence the RNA of monocytes, macrophages and other relevant haematopoietic cells/cell lines.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001030","title":"Whole_Genome_Sequencing_of_Gambian_severe_malaria_cases","description":"Genome sequencing of severe malaria cases (human) from the Gambia.","abstract":"500 Severe Malaria Cases from the Gambia will be sequenced to at least x10 coverage.  Human and, if possible, Plasmodium falciparum polymorphisms will be called.   This study forms part of the MalariaGEN Consortial Project 1, a project to investigate genetic resistance to malaria.  We will also investigate the parasite population in these cases and begin to look at genome interactions between both parasite and human.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001031","title":"Targeted resequencing of genetic lesion breakpoints and whole exome sequencing in BCR-ABL1/BCR-ABL1-like adult acute lymphoblastic leukemia","description":"In total 5 BCR-ABL1/BCR-ABL1-like ALL cases were characterized by whole exome sequencing (WES) and targeted sequencing of genetic lesion breakpoints as determined by DNA mapping arrays. Structural variants and copy number variation (CNV) analysis of the 5 BCR-ABL1/BCR-ABL1-like cases enabled the base-pair resolution detection of the breakpoints. Somatic variants were determined by directly comparing the WES data of the tumor material to WES data of the remission specimen.\n\nThorough analysis of the breakpoints revealed that they are characterized by proximal cryptic recombination signal sequence (cRSS) motifs. Additionally, these breakpoint loci are enriched for active chromatin markers analogous to antigen regions undergoing V(D)J rearrangements. Exhaustive mutations detection revealed complex insertion-deletion (indel) mutations in certain cRSS motifs as a consequence of erroneous cleavage by the RAG complex and subsequent error-prone non-homologous end joining repair. This novel mechanism of mutagenesis is revealed to recurrently target BTLA in these 5 BCR-ABL1/BCR-ABL1-like ALL cases.","abstract":"In total 5 BCR-ABL1/BCR-ABL1-like ALL cases were characterized by whole exome sequencing (WES) and targeted sequencing of genetic lesion breakpoints as determined by DNA mapping arrays. Structural variants and copy number variation (CNV) analysis of the 5 BCR-ABL1/BCR-ABL1-like cases enabled the base-pair resolution detection of the breakpoints. Somatic variants were determined by directly comparing the WES data of the tumor material to WES data of the remission specimen.\n\nThorough analysis of the breakpoints revealed that they are characterized by proximal cryptic recombination signal sequence (cRSS) motifs. Additionally, these breakpoint loci are enriched for active chromatin markers analogous to antigen regions undergoing V(D)J rearrangements. Exhaustive mutations detection revealed complex insertion-deletion (indel) mutations in certain cRSS motifs as a consequence of erroneous cleavage by the RAG complex and subsequent error-prone non-homologous end joining repair. This novel mechanism of mutagenesis is revealed to recurrently target BTLA in these 5 BCR-ABL1/BCR-ABL1-like ALL cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001032","title":"African Genome Variation Project (AGVP)","description":"Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterisation of African genetic diversity is needed. The African Genome Variation Project (AGVP) provides a resource to help design, implement and interpret genomic studies in sub-Saharan Africa (SSA) and worldwide. The AGVP represents dense genotypes from 1,481 and whole genome sequences (WGS) from 320 individuals across SSA. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across SSA.  We identify new loci under selection, including for malaria and hypertension. We show that modern imputation panels can identify association signals at highly differentiated loci across populations in SSA. Using WGS, we show further improvement in imputation accuracy supporting efforts for large-scale sequencing of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa, showing for the first time that such designs are feasible.","abstract":"Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterisation of African genetic diversity is needed. The African Genome Variation Project (AGVP) provides a resource to help design, implement and interpret genomic studies in sub-Saharan Africa (SSA) and worldwide. The AGVP represents dense genotypes from 1,481 and whole genome sequences (WGS) from 320 individuals across SSA. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across SSA.  We identify new loci under selection, including for malaria and hypertension. We show that modern imputation panels can identify association signals at highly differentiated loci across populations in SSA. Using WGS, we show further improvement in imputation accuracy supporting efforts for large-scale sequencing of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa, showing for the first time that such designs are feasible.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001033","title":"Spatial and temporal genomic evolution in glioblastoma","description":"Tumor heterogeneity is a challenging barrier to successful targeted therapy in glioblastoma. Identifying the mechanisms that drive cancer cells as they genetically evolve and adapt in response to treatment is a vital goal of modern cancer research. Analysis of sequencing data provides a method for uncovering the mechanisms sustaining tumor heterogeneity and driving evolution. Here, we analyzed genomic profiles of GBM biopsies taken from pre- and post-treatment GBMs (with matched germline controls), to understand 1) the intratumoral clonal compositions of primary GBM and 2) how GBM responds to therapeutic intervention. Our results provide a molecular portrait of GBM recurrence.","abstract":"Tumor heterogeneity is a challenging barrier to successful targeted therapy in glioblastoma. Identifying the mechanisms that drive cancer cells as they genetically evolve and adapt in response to treatment is a vital goal of modern cancer research. Analysis of sequencing data provides a method for uncovering the mechanisms sustaining tumor heterogeneity and driving evolution. Here, we analyzed genomic profiles of GBM biopsies taken from pre- and post-treatment GBMs (with matched germline controls), to understand 1) the intratumoral clonal compositions of primary GBM and 2) how GBM responds to therapeutic intervention. Our results provide a molecular portrait of GBM recurrence.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-11-09T22:14:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001034","title":"Gene-centric Association studies of Gall Bladder Disease using IBC array with 50K SNPs","description":"BACKGROUND","abstract":"BACKGROUND","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001035","title":"Identification_of_drug_resistance_genes_in_cancer_cell_lines_by_insertional_mutagenesis","description":"Our aim is to identify genes involved in resistance to anti-cancer therapies. In order to do this we have taken advantage of a lentiviral vector (LV)-based insertional mutagen to mutagenize cancer cell lines. LV-transduced cell lines were then treated with anti-cancer therapies and the emergence of resistant clones scored. DNA from pools of resistant clones was collected, subjected to custom capture by baits designed against the LV sequence, and then sequenced to identify the LV-genomic junction. We hope that the identification of recurrently targeted genes in resistant cell population will allow us to identify genes that mediate drug resistance.","abstract":"The effective treatment of cancer is currently complicated by intrinsic and acquired resistance to anti-caner therapies. Despite initial responses targeted therapies rarely result in disease eradication, and the emergence of drug-resistant clones provoke tumor relapse. The identification of genes and molecular pathways whose deregulation is associated with this resistance is required to facilitate the stratification of patients, and to more effectively personalized cancer therapy. Here we have used a lentiviral vector (LV) to mutagenize the genome of cancer cell lines thus making libraries of cell line clones that we then screened for drug resistance phenotypes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-11-12T09:56:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001036","title":"English Longitudinal Study of Ageing Genome-wide genotyping using the Illumina HumanOmni2.5-8","description":"These data are for a Genome Wide Association Study (GWAS) in the English Longitudinal Study of Ageing (ELSA, www.ifs.org.uk/elsa), building on the existing ELSA DNA Repository (EDNAR). This will establish a valuable resource for UK and international scientists, giving them access to GWAS genotyping data. Phenotype data, available on request, includes measures of personality, attitudes, behaviours as well as detailed social and economic outcomes; high quality biomarkers and other intermediate phenotypes; a range of more distal phenotypes, such as direct assessments of health (for example, hypertension, diabetes, muscle strength and cognitive function), and the opportunity to analyse existing biological samples for additional biomarkers, including metabolomic studies. Importantly, this resource would be matched with a near identical resource established in the United States for the Health and Retirement Study (HRS), giving the potential for high quality replication studies and comparative analyses.","abstract":"These data are for a Genome Wide Association Study (GWAS) in the English Longitudinal Study of Ageing (ELSA, www.ifs.org.uk/elsa), building on the existing ELSA DNA Repository (EDNAR). This will establish a valuable resource for UK and international scientists, giving them access to GWAS genotyping data. Phenotype data, available on request, includes measures of personality, attitudes, behaviours as well as detailed social and economic outcomes; high quality biomarkers and other intermediate phenotypes; a range of more distal phenotypes, such as direct assessments of health (for example, hypertension, diabetes, muscle strength and cognitive function), and the opportunity to analyse existing biological samples for additional biomarkers, including metabolomic studies. Importantly, this resource would be matched with a near identical resource established in the United States for the Health and Retirement Study (HRS), giving the potential for high quality replication studies and comparative analyses.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-11-13T12:35:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001037","title":"Yeast_KO_Seq_Strategy_1___PART2__Mutational_signatures_of_DNA_damage_and_repair_processes","description":"Mutational signatures attributable to all viable S.cerevisiae gene knockouts (approx. 4000) will be determined. 8 samples from each knockout will be grown. The 8 samples will then be pooled, with WGS performed to higher coverage on the resulting pooled sample.","abstract":"This work is part of the broader WTSA investigating mutational signatures of DNA damage and repair processes. Mutational signatures attributable to all viable S.cerevisiae will be determined.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001038","title":"Yeast_KO_Seq_Strategy_1___PART3__Mutational_signatures_of_DNA_damage_and_repair_processes","description":"Mutational signatures attributable to all viable S.cerevisiae gene knockouts (approx. 4000) will be determined. 8 samples from each knockout will be grown. The 8 samples will then be pooled, with WGS performed to higher coverage on the resulting pooled sample.","abstract":"This work is part of the broader WTSA investigating mutational signatures of DNA damage and repair processes. Mutational signatures attributable to all viable S.cerevisiae will be determined.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001039","title":"Yeast_KO_Seq_Strategy_1___PART4__Mutational_signatures_of_DNA_damage_and_repair_processes","description":"Mutational signatures attributable to all viable S.cerevisiae gene knockouts (approx. 4000) will be determined. 8 samples from each knockout will be grown. The 8 samples will then be pooled, with WGS performed to higher coverage on the resulting pooled sample.","abstract":"This work is part of the broader WTSA investigating mutational signatures of DNA damage and repair processes. Mutational signatures attributable to all viable S.cerevisiae will be determined.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001040","title":"Yeast_KO_Seq_Strategy_1___PART5__Mutational_signatures_of_DNA_damage_and_repair_processes","description":"Mutational signatures attributable to all viable S.cerevisiae gene knockouts (approx. 4000) will be determined. 8 samples from each knockout will be grown. The 8 samples will then be pooled, with WGS performed to higher coverage on the resulting pooled sample.","abstract":"This work is part of the broader WTSA investigating mutational signatures of DNA damage and repair processes. Mutational signatures attributable to all viable S.cerevisiae will be determined.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001041","title":"Spatio-temporal evolution of the primary glioblastoma genome","description":"Tumor recurrence following treatment is the major cause of mortality for glioblastoma multiforme (GBM) patients. Thus, insights on the evolutionary process at recurrence are critical for improved patient care. Here, we describe our genomic analyses of 38 GBM patients with the initial and recurrent tumor specimens for each individual. A substantial divergence in the landscape of driver alterations was associated with distant appearance of a recurrent tumor from the initial tumor, suggesting that the genomic profile of the initial tumor can mislead targeted therapies for the distally recurred tumor. In addition, in contrast to IDH1-mutated gliomas, IDH1-wild-type primary GBMs rarely developed hypermutation following temozolomide (TMZ) treatment, indicating low risk of TMZ-induced hypermutation for these patients under the standard regimen.","abstract":"Tumor recurrence following treatment is the major cause of mortality for glioblastoma multiforme (GBM) patients. Thus, insights on the evolutionary process at recurrence are critical for improved patient care. Here, we describe our genomic analyses of 38 GBM patients with the initial and recurrent tumor specimens for each individual. A substantial divergence in the landscape of driver alterations was associated with distant appearance of a recurrent tumor from the initial tumor, suggesting that the genomic profile of the initial tumor can mislead targeted therapies for the distally recurred tumor. In addition, in contrast to IDH1-mutated gliomas, IDH1-wild-type primary GBMs rarely developed hypermutation following temozolomide (TMZ) treatment, indicating low risk of TMZ-induced hypermutation for these patients under the standard regimen.","study_type":"Other","pubmed_ids":[26373279,27270107],"external_links":null,"is_released":true,"released_date":"2014-11-17T02:40:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001042","title":"Genomic Alterations in Gingivo-buccal Cancer: ICGC-India Project","description":"As a member of the International Cancer Genome Consortium (ICGC), India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India. There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection.  Paired DNA samples – isolated from the tumour tissue and from the blood of oral cancer patients – are being analysed to catalogue germline and somatic mutations. Association between each observed genomic alteration and exposure to environmental risk factors is being explored.   Detailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from blood and tumour tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai. Deep exome and whole genome sequencing are being performed at the National Institute of Biomedical Genomics, Kalyani. In addition, we are using Illumina Omni 2.5 SNP-chips to generate genotype and copy number alteration data.","abstract":"As a member of the International Cancer Genome Consortium (ICGC), India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India. There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection.  Paired DNA samples – isolated from the tumour tissue and from the blood of oral cancer patients – are being analysed to catalogue germline and somatic mutations. Association between each observed genomic alteration and exposure to environmental risk factors is being explored.   Detailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from blood and tumour tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai. Deep exome and whole genome sequencing are being performed at the National Institute of Biomedical Genomics, Kalyani. In addition, we are using Illumina Omni 2.5 SNP-chips to generate genotype and copy number alteration data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001043","title":"Yeast_KO_Seq_Strategy_1___PILOT_FOR_STRATEGY_2_COMPARISON__Mutational_signatures_of_DNA_damage_and_repair_processes","description":"Part of a pilot study to compare 2 sequencing strategies. This will inform sequencing strategy for further work on the mutational signatures project, which seeks to identify mutational signatures attributable to all viable S.cerevisiae gene knockouts (approx. 4000). In this study, 8 samples from each knockout will be grown from single propagation line with a ~10,000 cell bottleneck. These will then be sequenced 96 samples per lane (12 strains/8 colonies per strain).  Data will then be compared against the same knockout strains sequenced as per SScape Study 3318.","abstract":"This work is part of the broader WTSA investigating mutational signatures of DNA damage and repair processes.Mutational signatures attributable to all viable S.cerevisiae gene knockouts will be determined.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001044","title":"To reveal the spectrum of gene mutations in grade II/III gliomas, whole exome sequencing of 52 samples including 4 multi-regional and 10 multi-time points sampling cases and 291 SNP-array were performed.","description":"To reveal the spectrum of gene mutations in grade II/III gliomas, whole exome sequencing of 52 samples including 4 multi-regional and 10 multi-time points sampling cases and 291 SNP-array were performed. Our analysis revealed high degrees of temporal/spatial heterogeneity generated during tumor expansion and relapse.","abstract":"To reveal the spectrum of gene mutations in grade II/III gliomas, whole exome sequencing of 52 samples including 4 multi-regional and 10 multi-time points sampling cases and 291 SNP-array were performed. Our analysis revealed high degrees of temporal/spatial heterogeneity generated during tumor expansion and relapse.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-11-19T03:05:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001045","title":"To reveal the spectrum of gene mutations in grade II/III gliomas, whole exome sequencing of 52 samples including 4 multi-regional and 10 multi-time points sampling cases and 293 SNP-array were performed.","description":"To reveal the spectrum of gene mutations in grade II/III gliomas, whole exome sequencing of 52 samples including 4 multi-regional and 10 multi-time points sampling cases and 293 SNP-array were performed. Our analysis revealed high degrees of temporal/spatial heterogeneity generated during tumor expansion and relapse.","abstract":"To reveal the spectrum of gene mutations in grade II/III gliomas, whole exome sequencing of 52 samples including 4 multi-regional and 10 multi-time points sampling cases and 293 SNP-array were performed. Our analysis revealed high degrees of temporal/spatial heterogeneity generated during tumor expansion and relapse.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-08-13T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001046","title":"Finnish_population_cohort_genotyping_A","description":"The FINRISK cohorts comprise the respondents of representative, cross-sectional populationsurveys that are carried out every 5 years since 1972, to assess the risk factors of chronicdiseases (e.g. CVD, diabetes, obesity, cancer) and health behavior in the working agepopulation, in 3-5 large study areas of Finland. DNA samples were collected in the followingsurvey years: 1987, 1992, 1997, 2002, 2007, and 2012. The MONICA and EHES (EU)procedures were applied in phenotype collection (cf. MORGAM) and a wide spectrum oflaboratory tests was carried out from serum and plasma samples. Background information onsocioeconomic status, medical history, diet, exercise, measured anthropometric measures,etc. was collected by questionnaires and during a clinical visit. Plasma/serum samples arestill available for the 2002-2012 cohorts. The cohort sizes are 6000-8800 per survey. Thecohorts have been followed up by linking them to the national hospital discharge register,causes-of-death register and cancer register.This project is an extension to previous efforts to build a catalogue of Finnish genome widedata on population-based Finsrisk samples with rich phenotypic characterisations and healthregistry link-up. These samples will extend the current Sequencing Initiative Suomi (SISu)samples with a combination of genotyping using Illumina HumanCoreExome array and SISu-based imputation. This will lead to high confidence common and low frequency variantcatalogue. The project will be funded by Aarno Palotie’s remaining faculty fundscomplemented by Finnish funding from FIMM.Population based samples from the Finnish population. Finrisk study, see","abstract":"Population based samples from the Finnish population. Finrisk study, see www.nationalbiobanks.fi","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001047","title":"Finnish_population_cohort_genotyping_B","description":"The FINRISK cohorts comprise the respondents of representative, cross-sectional populationsurveys that are carried out every 5 years since 1972, to assess the risk factors of chronicdiseases (e.g. CVD, diabetes, obesity, cancer) and health behavior in the working agepopulation, in 3-5 large study areas of Finland. DNA samples were collected in the followingsurvey years: 1987, 1992, 1997, 2002, 2007, and 2012. The MONICA and EHES (EU)procedures were applied in phenotype collection (cf. MORGAM) and a wide spectrum oflaboratory tests was carried out from serum and plasma samples. Background information onsocioeconomic status, medical history, diet, exercise, measured anthropometric measures,etc. was collected by questionnaires and during a clinical visit. Plasma/serum samples arestill available for the 2002-2012 cohorts. The cohort sizes are 6000-8800 per survey. Thecohorts have been followed up by linking them to the national hospital discharge register,causes-of-death register and cancer register.This project is an extension to previous efforts to build a catalogue of Finnish genome widedata on population-based Finsrisk samples with rich phenotypic characterisations and healthregistry link-up. These samples will extend the current Sequencing Initiative Suomi (SISu)samples with a combination of genotyping using Illumina HumanCoreExome array and SISu-based imputation. This will lead to high confidence common and low frequency variantcatalogue. The project will be funded by Aarno Palotie’s remaining faculty fundscomplemented by Finnish funding from FIMM.","abstract":"The FINRISK cohorts comprise the respondents of representative, cross-sectional populationsurveys that are carried out every 5 years since 1972, to assess the risk factors of chronicdiseases (e.g. CVD, diabetes, obesity, cancer) and health behavior in the working agepopulation, in 3-5 large study areas of Finland. DNA samples were collected in the followingsurvey years: 1987, 1992, 1997, 2002, 2007, and 2012. The MONICA and EHES (EU)procedures were applied in phenotype collection (cf. MORGAM) and a wide spectrum oflaboratory tests was carried out from serum and plasma samples. Background information onsocioeconomic status, medical history, diet, exercise, measured anthropometric measures,etc. was collected by questionnaires and during a clinical visit. Plasma/serum samples arestill available for the 2002-2012 cohorts. The cohort sizes are 6000-8800 per survey. Thecohorts have been followed up by linking them to the national hospital discharge register,causes-of-death register and cancer register.This project is an extension to previous efforts to build a catalogue of Finnish genome widedata on population-based Finsrisk samples with rich phenotypic characterisations and healthregistry link-up. These samples will extend the current Sequencing Initiative Suomi (SISu)samples with a combination of genotyping using Illumina HumanCoreExome array and SISu-based imputation. This will lead to high confidence common and low frequency variantcatalogue. The project will be funded by Aarno Palotie’s remaining faculty fundscomplemented by Finnish funding from FIMM.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-11-19T12:41:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001048","title":"Preeclampsia InterPregGen Consortium: GWAS meta-analysis summary statistics for European fetal preeclampsia cases versus controls and GWAS genotype data for European fetal preeclampsia cases","description":null,"abstract":"Preeclampsia (PE) is a syndrome affecting pregnant mothers and fetus/babies characterised by hypertension and proteinuria, and is a leading cause of maternal and fetal death and of premature births worldwide. The InterPregGen Consortium was funded by a European Framework 7 (FP7) grant and grew out of the WTCCC3 GWAS comparing ~2000 UK PE mothers with ~6000 common UK controls. The EGAS00001001048 study is a GWAS meta-analysis of UK and Icelandic PE fetal (baby) cases versus controls and is one component of the InterPregGen FP7 project.","study_type":"Other","pubmed_ids":[28628106],"external_links":null,"is_released":true,"released_date":"2014-11-19T12:59:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001049","title":"Extension_of_meningitis","description":"We have recently generated GWAS data on 885 cases of bacterial meningitis (with bacterialcultures for sequencing) in collaboration with a group in Amsterdam. Sanger co-funded thosedata, and we've used publicly available controls in our analysis. Our collaborators haverecruited another 94 cases, and we'd like to GWAS them and add them to the analysis(sample size boost of 10%)","abstract":"We have recently generated GWAS data on 885 cases of bacterial meningitis (with bacterialcultures for sequencing) in collaboration with a group in Amsterdam. Sanger co-funded thosedata, and we've used publicly available controls in our analysis. Our collaborators haverecruited another 94 cases, and we'd like to GWAS them and add them to the analysis(sample size boost of 10%)","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001050","title":"CONSERTING: an accurate method for detecting somatic DNA copy number alterations in whole genome sequencing data","description":"Whole genome sequencing (WGS) enables comprehensive identification of DNA copy number alterations (CNAs) in cancer genomes. The recently described phenomenom of “chromothripsis” shows that oscilliating CNAs at multiple genomic loci may arise from a single complex re-arrangement, thereby requiring integration of structural variations (SVs) to fully understand their pathological effect. Here we describe CONSERTING, a novel algorithm for integrative WGS analysis of CNAs and SVs in cancer through iterative analysis of segmentation by read depth change and local SV detection. Analysis of 43 paired tumor/normal WGS cancer datasets from pediatric and adult cancer demonstrated much higher sensitivity and accuracy for CONSERTING than four commonly used somatic CNA detection algorithms or single nucleotide polymorphism arrays. Discovery of a novel oncogenic deletion in NOTCH1 and chromothripsis-like SVs and CNAs in tumor subclones demonstrates the power of this approach in cancer genome analysis.","abstract":"Whole genome sequencing (WGS) enables comprehensive identification of DNA copy number alterations (CNAs) in cancer genomes. The recently described phenomenom of “chromothripsis” shows that oscilliating CNAs at multiple genomic loci may arise from a single complex re-arrangement, thereby requiring integration of structural variations (SVs) to fully understand their pathological effect. Here we describe CONSERTING, a novel algorithm for integrative WGS analysis of CNAs and SVs in cancer through iterative analysis of segmentation by read depth change and local SV detection. Analysis of 43 paired tumor/normal WGS cancer datasets from pediatric and adult cancer demonstrated much higher sensitivity and accuracy for CONSERTING than four commonly used somatic CNA detection algorithms or single nucleotide polymorphism arrays. Discovery of a novel oncogenic deletion in NOTCH1 and chromothripsis-like SVs and CNAs in tumor subclones demonstrates the power of this approach in cancer genome analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001051","title":"Methylation differences in trisomy 21 using monozygotic twins","description":"We have hypothesized that methylation differences induced by trisomy 21 (T21) contribute to the phenotypic characteristics and heterogeneity in T21. In order to determine the methylation differences in T21 without the interference of the interindividual genomic variation, we have used fetal skin fibroblasts from monozygotic (MZ) twins discordant for T21. We also used skin fibroblasts from MZ twins concordant for T21, normal MZ twins without T21, and unrelated normal and T21 individuals. We applied Reduced Representation Bisulfite Sequencing (RRBS) to generate genome wide nucleotide resolution of DNA methylation based on high throughput sequencing between each pair of samples. RRBS revealed differentially methylated promoter regions (DMRs) in MZ twins discordant for T21 that have also been observed in unrelated normal and T21 individuals. The identified DMRs are enriched for genes involved in embryonic organ morphogenesis. These DMRs are maintained in iPS cells generated from this twin pair and are correlated with the gene expression changes. We have also observed an increase in DNA methylation level in the T21 methylome compared to the normal euploid methylome. This observation is concordant with the up regulation of DNA methyltransferase enzymes (DNMT3B and DNMT3L) and down regulation of DNA demethylation enzymes (TET2 and TET3) in the iPSC of the T21 versus normal twin. Additionally, two sets of T21 MZ twins discordant for heart defect highlighted DMRs in genes that are associated with heart development. In conclusion the study of DNA methylation differences in MZ twins discordant for genomic abnormalities is a promising approach to understand the molecular pathophysiology of aneuploidies.","abstract":"We have hypothesized that methylation differences induced by trisomy 21 (T21) contribute to the phenotypic characteristics and heterogeneity in T21. In order to determine the methylation differences in T21 without the interference of the interindividual genomic variation, we have used fetal skin fibroblasts from monozygotic (MZ) twins discordant for T21. We also used skin fibroblasts from MZ twins concordant for T21, normal MZ twins without T21, and unrelated normal and T21 individuals. We applied Reduced Representation Bisulfite Sequencing (RRBS) to generate genome wide nucleotide resolution of DNA methylation based on high throughput sequencing between each pair of samples. RRBS revealed differentially methylated promoter regions (DMRs) in MZ twins discordant for T21 that have also been observed in unrelated normal and T21 individuals. The identified DMRs are enriched for genes involved in embryonic organ morphogenesis. These DMRs are maintained in iPS cells generated from this twin pair and are correlated with the gene expression changes. We have also observed an increase in DNA methylation level in the T21 methylome compared to the normal euploid methylome. This observation is concordant with the up regulation of DNA methyltransferase enzymes (DNMT3B and DNMT3L) and down regulation of DNA demethylation enzymes (TET2 and TET3) in the iPSC of the T21 versus normal twin. Additionally, two sets of T21 MZ twins discordant for heart defect highlighted DMRs in genes that are associated with heart development. In conclusion the study of DNA methylation differences in MZ twins discordant for genomic abnormalities is a promising approach to understand the molecular pathophysiology of aneuploidies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-11-26T07:46:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001052","title":"Skin Adenocarcinoma Genome Sequencing","description":"Skin Adenocarcinoma Genome Sequencing","abstract":"Skin Adenocarcinoma Genome Sequencing","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-12-01T19:05:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001053","title":"Somatic_mutations_in_oesophageal_epithelium","description":"Deep targeted sequencing of oesophageal epithelium to identify subclonal mutations.","abstract":"In this study we will perform ultra-deep targeted sequencing to identify somatic mutations in oesophageal epithelium.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001054","title":"GIST_SSGXVIII_trial_targeted_gene_sequencing","description":"Targeted cancer gene sequencing of samples enrolled in the SSGXVIII trial from Finland.","abstract":"Targeted cancer gene sequencing of samples enrolled in the SSGXVIII trial from Finland.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-12-02T14:49:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001055","title":"Total RNA sequencing of two people","description":"We sequenced  total RNA  of two pairs  cancer of chinese，and each sample hase about 15M clean reads.","abstract":"We sequenced  total RNA  of two pairs  cancer of chinese，and each sample hase about 15M clean reads.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001056","title":"WGS and WES of 78 pairs Chinese gastric cancer","description":"Gastric Cancer (GC) is a highly heterogeneous disease. To identify potential clinically actionable therapeutic targets that may inform individualized treatment strategies, we performed whole-exome sequencing on 78 GCs of differing histologies and anatomic locations, as well as whole-genome sequencing on two GC cases, each with 3 primary tumours and 2 matching lymph node metastases. The data showed two distinct GC subtypes with either high-clonality (HiC) or low-clonality (LoC).","abstract":"Gastric Cancer (GC) is a highly heterogeneous disease. To identify potential clinically actionable therapeutic targets that may inform individualized treatment strategies, we performed whole-exome sequencing on 78 GCs of differing histologies and anatomic locations, as well as whole-genome sequencing on two GC cases, each with 3 primary tumours and 2 matching lymph node metastases. The data showed two distinct GC subtypes with either high-clonality (HiC) or low-clonality (LoC).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-12-04T10:13:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001057","title":"Total RNA sequencing of two people","description":"We sequenced  total RNA  of two pairs  cancer of chinese，and each sample hase about 15M clean reads.","abstract":"We sequenced  total RNA  of two pairs  cancer of chinese，and each sample hase about 15M clean reads.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001058","title":"Total RNA sequencing of two people","description":"We sequenced  total RNA  of two pairs  cancer of chinese，and each sample hase about 15M clean reads","abstract":"We sequenced  total RNA  of two pairs  cancer of chinese，and each sample hase about 15M clean reads","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001059","title":"Cell_lines_with_telomere_fusion_induced_rearrangements","description":"Whole-genome somatic rearrangement and point mutation analysis in cell lines with induced telomere fusions.","abstract":"Whole-genome somatic rearrangement and point mutation analysis in cell lines with induced telomere fusions.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-12-04T12:02:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001060","title":"CRISPR_screen_M14__NCI_H3122","description":"Genome wide CRISPR screen was performed to find resistance to targeted drugs for melanoma and lung","abstract":"Genome wide CRISPR screen was performed to find resistance to targeted drugs for melanoma and lung","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-12-04T12:15:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001061","title":"Mouse_somatic_mutations_in_normal_tissue","description":"This pilot contains 10 samples from 1 wildtype mouse plus 1 sample for each parent for whole genome sequencing.","abstract":"This is a pilot for the mouse lineage project, in which we try to determine the lineage of (wildtype) mouse cells.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001062","title":"Total RNA sequencing of two people","description":"We sequenced  total RNA  of two pairs  cancer of chinese，and each sample hase about 15M clean reads.","abstract":"We sequenced  total RNA  of two pairs  cancer of chinese，and each sample hase about 15M clean reads.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001063","title":"Total RNA sequencing of two people","description":"We sequenced  total RNA  of two pairs  cancer of chinese，and each sample hase about 15M clean reads.","abstract":"We sequenced  total RNA  of two pairs  cancer of chinese，and each sample hase about 15M clean reads.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001064","title":"Total RNA sequencing of two people","description":"We sequenced  total RNA  of two pairs  cancer of chinese，and each sample hase about 15M clean reads.","abstract":"We sequenced  total RNA  of two pairs  cancer of chinese，and each sample hase about 15M clean reads.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001065","title":"Whole WGS sequencing of Chinese gastric cancer case","description":"Whole WGS sequencing and WES of Chinese gastric cancer case","abstract":"Whole WGS sequencing and WES of Chinese gastric cancer case","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001066","title":"Genome-wide SNP genotyping and DNA methylation epigenotyping of African rainforest hunter-gatherers and neighbouring agriculturalists","description":"The epigenomic landscape of the human genome, in particular DNA methylation, is increasingly recognised as an important driver of phenotypic diversity in health and disease. However, the impact that genetic variation and changes in lifestyle and ecological habitat have on this epigenetic mark remains unknown. To address this question, we analysed genome-wide SNP and DNA methylation profiles of 362 individuals from African populations of rainforest hunter-gatherers and sedentary farmers with different past and present lifestyles and ecologies.","abstract":"The epigenomic landscape of the human genome, in particular DNA methylation, is increasingly recognised as an important driver of phenotypic diversity in health and disease. However, the impact that genetic variation and changes in lifestyle and ecological habitat have on this epigenetic mark remains unknown. To address this question, we analysed genome-wide SNP and DNA methylation profiles of 362 individuals from African populations of rainforest hunter-gatherers and sedentary farmers with different past and present lifestyles and ecologies.","study_type":"Other","pubmed_ids":[26616214],"external_links":null,"is_released":true,"released_date":"2014-12-05T08:43:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001067","title":"Integrated genomic, transcriptional and epigenomic analyses in germinal center-cell lymphomas link the mutation landscape with differential DNA methylation in Burkitt lymphoma","description":"Biologically and clinically diverse B-cell neoplasms, including Burkitt, follicular and diffuse large B-cell lymphoma, show features of germinal center (GC) B-cells. Here we present a comprehensive analysis of the epigenetic landscape of GC-B-cell lymphomas using whole genome bisulfite sequencing paired with genome and transcriptome sequencing from 29 primary tumor samples and four normal GC-B-cell samples. All lymphomas studied showed extensive genome-wide methylation losses as well as intragenic regions where DNA methylation levels were strongly correlated with expression of associated genes. Pathway analysis revealed that these intragenic regions were enriched in signaling networks differentially activated in Burkitt and follicular lymphomas and affected regulatory mechanisms deregulated by recurrent mutations in a large fraction of Burkitt lymphomas (including the ID3/TCF3 complex, the SWI/SNF remodeling complex and the inhibitory GI signaling pathway). Taken together, these results provide a global picture of Burkitt lymphoma pathomechanism and demonstrate a tight connection between epigenetic regulation and other levels of regulatory control in these tumors.","abstract":"Biologically and clinically diverse B-cell neoplasms, including Burkitt, follicular and diffuse large B-cell lymphoma, show features of germinal center (GC) B-cells. Here we present a comprehensive analysis of the epigenetic landscape of GC-B-cell lymphomas using whole genome bisulfite sequencing paired with genome and transcriptome sequencing from 29 primary tumor samples and four normal GC-B-cell samples. All lymphomas studied showed extensive genome-wide methylation losses as well as intragenic regions where DNA methylation levels were strongly correlated with expression of associated genes. Pathway analysis revealed that these intragenic regions were enriched in signaling networks differentially activated in Burkitt and follicular lymphomas and affected regulatory mechanisms deregulated by recurrent mutations in a large fraction of Burkitt lymphomas (including the ID3/TCF3 complex, the SWI/SNF remodeling complex and the inhibitory GI signaling pathway). Taken together, these results provide a global picture of Burkitt lymphoma pathomechanism and demonstrate a tight connection between epigenetic regulation and other levels of regulatory control in these tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-12-08T14:27:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001068","title":"Exome Sequencing Reveals Frequent Inactivating Mutations in BAP1, ARID1A, and PBRM1 in Intrahepatic Cholangiocarcinomas","description":"Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin remodeling genes (including BAP1, ARID1A, and PBRM1) – mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in genes encoding the metabolic enzymes IDH1 and IDH2 in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These studies highlight the importance of dysregulation of chromatin remodeling in intrahepatic cholangiocarcinomas.","abstract":"Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin remodeling genes (including BAP1, ARID1A, and PBRM1) – mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in genes encoding the metabolic enzymes IDH1 and IDH2 in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These studies highlight the importance of dysregulation of chromatin remodeling in intrahepatic cholangiocarcinomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001069","title":"Exome Sequencing Reveals Frequent Inactivating Mutations in BAP1, ARID1A, and PBRM1 in Intrahepatic Cholangiocarcinomas","description":"Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin remodeling genes (including BAP1, ARID1A, and PBRM1) – mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in genes encoding the metabolic enzymes IDH1 and IDH2 in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These studies highlight the importance of dysregulation of chromatin remodeling in intrahepatic cholangiocarcinomas.","abstract":"Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin remodeling genes (including BAP1, ARID1A, and PBRM1) – mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in genes encoding the metabolic enzymes IDH1 and IDH2 in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These studies highlight the importance of dysregulation of chromatin remodeling in intrahepatic cholangiocarcinomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001070","title":"Exome Sequencing Reveals Frequent Inactivating Mutations in BAP1, ARID1A, and PBRM1 in Intrahepatic Cholangiocarcinomas","description":"Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin remodeling genes (including BAP1, ARID1A, and PBRM1) – mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in genes encoding the metabolic enzymes IDH1 and IDH2 in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These studies highlight the importance of dysregulation of chromatin remodeling in intrahepatic cholangiocarcinomas.","abstract":"Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin remodeling genes (including BAP1, ARID1A, and PBRM1) – mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in genes encoding the metabolic enzymes IDH1 and IDH2 in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These studies highlight the importance of dysregulation of chromatin remodeling in intrahepatic cholangiocarcinomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001071","title":"Exome Sequencing Reveals Frequent Inactivating Mutations in BAP1, ARID1A, and PBRM1 in Intrahepatic Cholangiocarcinomas","description":"Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin remodeling genes (including BAP1, ARID1A, and PBRM1) – mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in genes encoding the metabolic enzymes IDH1 and IDH2 in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These studies highlight the importance of dysregulation of chromatin remodeling in intrahepatic cholangiocarcinomas.","abstract":"Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin remodeling genes (including BAP1, ARID1A, and PBRM1) – mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in genes encoding the metabolic enzymes IDH1 and IDH2 in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These studies highlight the importance of dysregulation of chromatin remodeling in intrahepatic cholangiocarcinomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001072","title":"Exome Sequencing Reveals Frequent Inactivating Mutations in BAP1, ARID1A, and PBRM1 in Intrahepatic Cholangiocarcinomas","description":"Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin remodeling genes (including BAP1, ARID1A, and PBRM1) – mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in genes encoding the metabolic enzymes IDH1 and IDH2 in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These studies highlight the importance of dysregulation of chromatin remodeling in intrahepatic cholangiocarcinomas.","abstract":"Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin remodeling genes (including BAP1, ARID1A, and PBRM1) – mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in genes encoding the metabolic enzymes IDH1 and IDH2 in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These studies highlight the importance of dysregulation of chromatin remodeling in intrahepatic cholangiocarcinomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001073","title":"Whole-exome sequencing of Pituitary Cushing's Disease","description":"Cushing’s disease, which is caused by excess production of adrenocorticotropic hormone (ACTH) from pituitary tumors, is the majority of endogenous Cushing’s syndrome. Critical genetic alterations of Cushing’s disease remain unclear. We performed whole-exome sequencing in 20 ACTH-secreting pituitary adenomas.","abstract":"Cushing’s disease, which is caused by excess production of adrenocorticotropic hormone (ACTH) from pituitary tumors, is the majority of endogenous Cushing’s syndrome. Critical genetic alterations of Cushing’s disease remain unclear. We performed whole-exome sequencing in 20 ACTH-secreting pituitary adenomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001074","title":"The aim of this study was to look for novel candidate genes for Congenital Muscular Dystrophy","description":"Congenital Muscular Dystrophies (CMD) are a heterogeneous group of rare inherited neuromuscular disorders. The estimated incidence and prevalence for CMD is 4.65/100,000 and 0.68/100,000 respectively, although these are probably an underestimate. Patients present at birth or within the first few months of life with hypotonia and muscle weakness. Other features include eye and brain abnormalities, joint contractures, respiratory and cardiac involvement and skin changes. The majority are severely progressive and there is no treatment available. There are 24 known causative genes (LAMA2, COL6A1, COL6A2, COL6A3, COL12A1, ITGA7, ITGA9, SEPN1, LMNA, CHKB, POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, DPM3, DPM2, DAG1, DOLK, ISPD, B3GNT1, B3GALNT2, GMPPB) . Except for collagen genes and LMNA, in most cases mutations are inherited in an autosomal recessive fashion. Several of these genes have been identified very recently by Whole-Exome-Sequencing (for example COL12A1, B3GALNT2 and GMPPB) demonstrating the suitability of this technique in the field of muscular dystrophies. However, there are patients in whom all known genetic forms have been excluded which are clinically and pathologically undistinguishable from genetically defined forms. A recent study of the UK population indicates that collagen VI defects are the most common subgroup (which is also our experience in the Spanish population).  However, in that same study a genetic diagnosis could not be reached in 50% of CMD cases after testing of all genes. Diagnosis is based on clinical assessment and analysis of muscle biopsy or fibroblast cultures using antibodies that recognise the primary or secondary defective proteins such as collagen VI, α-dystroglycan and laminin-α2, although these are not always conclusive and there is overlap between different forms (for example in the dystroglycanopathies). Brain and muscle magnetic resonance imaging can also help towards diagnosis. A combination of these techniques is used to guide gene sequencing which is often done one a gene by gene basis or sometimes using panels for a selection of genes. Prenatal diagnosis can be performed in some cases.","abstract":"Congenital Muscular Dystrophies (CMD) are a heterogeneous group of rare inherited neuromuscular disorders. The estimated incidence and prevalence for CMD is 4.65/100,000 and 0.68/100,000 respectively, although these are probably an underestimate. Patients present at birth or within the first few months of life with hypotonia and muscle weakness. Other features include eye and brain abnormalities, joint contractures, respiratory and cardiac involvement and skin changes. The majority are severely progressive and there is no treatment available. There are 24 known causative genes (LAMA2, COL6A1, COL6A2, COL6A3, COL12A1, ITGA7, ITGA9, SEPN1, LMNA, CHKB, POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, DPM3, DPM2, DAG1, DOLK, ISPD, B3GNT1, B3GALNT2, GMPPB) . Except for collagen genes and LMNA, in most cases mutations are inherited in an autosomal recessive fashion. Several of these genes have been identified very recently by Whole-Exome-Sequencing (for example COL12A1, B3GALNT2 and GMPPB) demonstrating the suitability of this technique in the field of muscular dystrophies. However, there are patients in whom all known genetic forms have been excluded which are clinically and pathologically undistinguishable from genetically defined forms. A recent study of the UK population indicates that collagen VI defects are the most common subgroup (which is also our experience in the Spanish population).  However, in that same study a genetic diagnosis could not be reached in 50% of CMD cases after testing of all genes. Diagnosis is based on clinical assessment and analysis of muscle biopsy or fibroblast cultures using antibodies that recognise the primary or secondary defective proteins such as collagen VI, α-dystroglycan and laminin-α2, although these are not always conclusive and there is overlap between different forms (for example in the dystroglycanopathies). Brain and muscle magnetic resonance imaging can also help towards diagnosis. A combination of these techniques is used to guide gene sequencing which is often done one a gene by gene basis or sometimes using panels for a selection of genes. Prenatal diagnosis can be performed in some cases.","study_type":"Other","pubmed_ids":[17878207,18691338,22975586,24223098],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001075","title":"The aim of this study was to identify novel candidate genes for Congenital Muscular Dystrophy","description":"Congenital Muscular Dystrophies (CMD) are a heterogeneous group of rare inherited neuromuscular disorders. The estimated incidence and prevalence for CMD is 4.65/100,000 and 0.68/100,000 respectively, although these are probably an underestimate. Patients present at birth or within the first few months of life with hypotonia and muscle weakness. Other features include eye and brain abnormalities, joint contractures, respiratory and cardiac involvement and skin changes. The majority are severely progressive and there is no treatment available. There are 24 known causative genes (LAMA2, COL6A1, COL6A2, COL6A3, COL12A1, ITGA7, ITGA9, SEPN1, LMNA, CHKB, POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, DPM3, DPM2, DAG1, DOLK, ISPD, B3GNT1, B3GALNT2, GMPPB) . Except for collagen genes and LMNA, in most cases mutations are inherited in an autosomal recessive fashion. Several of these genes have been identified very recently by Whole-Exome-Sequencing (for example COL12A1, B3GALNT2 and GMPPB) demonstrating the suitability of this technique in the field of muscular dystrophies. However, there are patients in whom all known genetic forms have been excluded which are clinically and pathologically undistinguishable from genetically defined forms. A recent study of the UK population indicates that collagen VI defects are the most common subgroup (which is also our experience in the Spanish population).  However, in that same study a genetic diagnosis could not be reached in 50% of CMD cases after testing of all genes. Diagnosis is based on clinical assessment and analysis of muscle biopsy or fibroblast cultures using antibodies that recognise the primary or secondary defective proteins such as collagen VI, α-dystroglycan and laminin-α2, although these are not always conclusive and there is overlap between different forms (for example in the dystroglycanopathies). Brain and muscle magnetic resonance imaging can also help towards diagnosis. A combination of these techniques is used to guide gene sequencing which is often done one a gene by gene basis or sometimes using panels for a selection of genes. Prenatal diagnosis can be performed in some cases.","abstract":"Congenital Muscular Dystrophies (CMD) are a heterogeneous group of rare inherited neuromuscular disorders. The estimated incidence and prevalence for CMD is 4.65/100,000 and 0.68/100,000 respectively, although these are probably an underestimate. Patients present at birth or within the first few months of life with hypotonia and muscle weakness. Other features include eye and brain abnormalities, joint contractures, respiratory and cardiac involvement and skin changes. The majority are severely progressive and there is no treatment available. There are 24 known causative genes (LAMA2, COL6A1, COL6A2, COL6A3, COL12A1, ITGA7, ITGA9, SEPN1, LMNA, CHKB, POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, DPM3, DPM2, DAG1, DOLK, ISPD, B3GNT1, B3GALNT2, GMPPB) . Except for collagen genes and LMNA, in most cases mutations are inherited in an autosomal recessive fashion. Several of these genes have been identified very recently by Whole-Exome-Sequencing (for example COL12A1, B3GALNT2 and GMPPB) demonstrating the suitability of this technique in the field of muscular dystrophies. However, there are patients in whom all known genetic forms have been excluded which are clinically and pathologically undistinguishable from genetically defined forms. A recent study of the UK population indicates that collagen VI defects are the most common subgroup (which is also our experience in the Spanish population).  However, in that same study a genetic diagnosis could not be reached in 50% of CMD cases after testing of all genes. Diagnosis is based on clinical assessment and analysis of muscle biopsy or fibroblast cultures using antibodies that recognise the primary or secondary defective proteins such as collagen VI, α-dystroglycan and laminin-α2, although these are not always conclusive and there is overlap between different forms (for example in the dystroglycanopathies). Brain and muscle magnetic resonance imaging can also help towards diagnosis. A combination of these techniques is used to guide gene sequencing which is often done one a gene by gene basis or sometimes using panels for a selection of genes. Prenatal diagnosis can be performed in some cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001076","title":"The aim of this project was to identify novel candidate genes for Congenital Muscular Dystrophy","description":"Congenital Muscular Dystrophies (CMD) are a heterogeneous group of rare inherited neuromuscular disorders. The estimated incidence and prevalence for CMD is 4.65/100,000 and 0.68/100,000 respectively, although these are probably an underestimate. Patients present at birth or within the first few months of life with hypotonia and muscle weakness. Other features include eye and brain abnormalities, joint contractures, respiratory and cardiac involvement and skin changes. The majority are severely progressive and there is no treatment available. There are 24 known causative genes (LAMA2, COL6A1, COL6A2, COL6A3, COL12A1, ITGA7, ITGA9, SEPN1, LMNA, CHKB, POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, DPM3, DPM2, DAG1, DOLK, ISPD, B3GNT1, B3GALNT2, GMPPB) . Except for collagen genes and LMNA, in most cases mutations are inherited in an autosomal recessive fashion. Several of these genes have been identified very recently by Whole-Exome-Sequencing (for example COL12A1, B3GALNT2 and GMPPB) demonstrating the suitability of this technique in the field of muscular dystrophies. However, there are patients in whom all known genetic forms have been excluded which are clinically and pathologically undistinguishable from genetically defined forms. A recent study of the UK population indicates that collagen VI defects are the most common subgroup (which is also our experience in the Spanish population).  However, in that same study a genetic diagnosis could not be reached in 50% of CMD cases after testing of all genes. Diagnosis is based on clinical assessment and analysis of muscle biopsy or fibroblast cultures using antibodies that recognise the primary or secondary defective proteins such as collagen VI, α-dystroglycan and laminin-α2, although these are not always conclusive and there is overlap between different forms (for example in the dystroglycanopathies). Brain and muscle magnetic resonance imaging can also help towards diagnosis. A combination of these techniques is used to guide gene sequencing which is often done one a gene by gene basis or sometimes using panels for a selection of genes. Prenatal diagnosis can be performed in some cases.","abstract":"Congenital Muscular Dystrophies (CMD) are a heterogeneous group of rare inherited neuromuscular disorders. The estimated incidence and prevalence for CMD is 4.65/100,000 and 0.68/100,000 respectively, although these are probably an underestimate. Patients present at birth or within the first few months of life with hypotonia and muscle weakness. Other features include eye and brain abnormalities, joint contractures, respiratory and cardiac involvement and skin changes. The majority are severely progressive and there is no treatment available. There are 24 known causative genes (LAMA2, COL6A1, COL6A2, COL6A3, COL12A1, ITGA7, ITGA9, SEPN1, LMNA, CHKB, POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, DPM3, DPM2, DAG1, DOLK, ISPD, B3GNT1, B3GALNT2, GMPPB) . Except for collagen genes and LMNA, in most cases mutations are inherited in an autosomal recessive fashion. Several of these genes have been identified very recently by Whole-Exome-Sequencing (for example COL12A1, B3GALNT2 and GMPPB) demonstrating the suitability of this technique in the field of muscular dystrophies. However, there are patients in whom all known genetic forms have been excluded which are clinically and pathologically undistinguishable from genetically defined forms. A recent study of the UK population indicates that collagen VI defects are the most common subgroup (which is also our experience in the Spanish population).  However, in that same study a genetic diagnosis could not be reached in 50% of CMD cases after testing of all genes. Diagnosis is based on clinical assessment and analysis of muscle biopsy or fibroblast cultures using antibodies that recognise the primary or secondary defective proteins such as collagen VI, α-dystroglycan and laminin-α2, although these are not always conclusive and there is overlap between different forms (for example in the dystroglycanopathies). Brain and muscle magnetic resonance imaging can also help towards diagnosis. A combination of these techniques is used to guide gene sequencing which is often done one a gene by gene basis or sometimes using panels for a selection of genes. Prenatal diagnosis can be performed in some cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001077","title":"The mission of the BIOS Consortium is to create a large-scale data infrastructure and to bring together BBMRI researchers focusing on integrative omics studies in Dutch Biobanks.","description":"The advent of the genome-wide association study (GWAS) led to the successful identification of thousands of variants that are robustly associated with complex disease phenotypes. Dutch biobanks played a substantial role in these discoveries. For most of these variants, however, the mechanisms through which they contribute to these phenotypes remain unknown. The BIOS Consortium applies a functional genomics approach that integrates genome-wide genetic data with data on the epigenome and transcriptome to elucidate these mechanisms. Over 4000 samples from BBMRI-NL biobanks with in-depth information on disease phenotypes and GWAS data are being enriched with RNA-sequencing and genome-wide DNA methylation data. The same is true for samples with whole-genome sequencing data from GoNL. This unique data infrastructure provides a powerful platform to evaluate key questions in integrative omics from establishing comprehensive eQTL and meQTL catalogues to linking molecular pathways across omics levels to phenotypic outcomes.","abstract":"The advent of the genome-wide association study (GWAS) led to the successful identification of thousands of variants that are robustly associated with complex disease phenotypes. Dutch biobanks played a substantial role in these discoveries. For most of these variants, however, the mechanisms through which they contribute to these phenotypes remain unknown. The BIOS Consortium applies a functional genomics approach that integrates genome-wide genetic data with data on the epigenome and transcriptome to elucidate these mechanisms. Over 4000 samples from BBMRI-NL biobanks with in-depth information on disease phenotypes and GWAS data are being enriched with RNA-sequencing and genome-wide DNA methylation data. The same is true for samples with whole-genome sequencing data from GoNL. This unique data infrastructure provides a powerful platform to evaluate key questions in integrative omics from establishing comprehensive eQTL and meQTL catalogues to linking molecular pathways across omics levels to phenotypic outcomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-12-09T14:26:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001078","title":"Characterization of the human adipose tissue epigenome by next-generation sequencing approaches","description":"DNA methylation variation is known to contribute to multifactorial disease susceptibility. As large sample sizes are needed to obtain sufficient power, most genome-wide methylation studies have used targeted arrays or enrichment methodologies preferentially covering CpG-dense regions. To overcome these limitations, we present a new approach, MethylC-Capture Sequencing (MCC-Seq), for customizable and cost-efficient sequencing of complete functional methylomes. We demonstrated the applicability of MCC-Seq to study human traits by identifying novel methylation variation within enhancers that are strongly correlated to plasma triglyceride (TG). To further pinpoint and fine-map the effects of the TG-associated CpGs we use RNA-Seq and ATAC-Seq from human adipocytes.","abstract":"DNA methylation variation is known to contribute to multifactorial disease susceptibility. As large sample sizes are needed to obtain sufficient power, most genome-wide methylation studies have used targeted arrays or enrichment methodologies preferentially covering CpG-dense regions. To overcome these limitations, we present a new approach, MethylC-Capture Sequencing (MCC-Seq), for customizable and cost-efficient sequencing of complete functional methylomes. We demonstrated the applicability of MCC-Seq to study human traits by identifying novel methylation variation within enhancers that are strongly correlated to plasma triglyceride (TG). To further pinpoint and fine-map the effects of the TG-associated CpGs we use RNA-Seq and ATAC-Seq from human adipocytes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001079","title":"Characterization of the human adipose epigenome by next-generation sequencing approaches","description":"DNA methylation variation is known to contribute to multifactorial disease susceptibility. As large sample sizes are needed to obtain sufficient power, most genome-wide methylation studies have used targeted arrays or enrichment methodologies preferentially covering CpG-dense regions. To overcome these limitations, we present a new approach, MethylC-Capture Sequencing (MCC-Seq), for customizable and cost-efficient sequencing of complete functional methylomes. To illustrate the approach, we generated an adipose tissue (AT) specific MCC-Seq panel covering the functional methylome in AT. We demonstrated the applicability of MCC-Seq to study human traits by identifying novel methylation variation within enhancers that are strongly correlated to plasma triglyceride (TG) and used RNA-Seq and ATAC-Seq from human adipocytes to further pinpoint and fine-map the effects of the TG-associated CpGs.","abstract":"DNA methylation variation is known to contribute to multifactorial disease susceptibility. As large sample sizes are needed to obtain sufficient power, most genome-wide methylation studies have used targeted arrays or enrichment methodologies preferentially covering CpG-dense regions. To overcome these limitations, we present a new approach, MethylC-Capture Sequencing (MCC-Seq), for customizable and cost-efficient sequencing of complete functional methylomes. To illustrate the approach, we generated an adipose tissue (AT) specific MCC-Seq panel covering the functional methylome in AT. We demonstrated the applicability of MCC-Seq to study human traits by identifying novel methylation variation within enhancers that are strongly correlated to plasma triglyceride (TG) and used RNA-Seq and ATAC-Seq from human adipocytes to further pinpoint and fine-map the effects of the TG-associated CpGs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001080","title":"Blood","description":"Blood","abstract":"Blood","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001081","title":"blood","description":"blood","abstract":"blood","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001082","title":"2014 chunnam AML analysis","description":"2014 AML analysis is conducted with samples collected from Chunnam universty. \n67 paired samples are belong to this project.\nThe study was designed to examine the molecular abnormalities from leukemic patients at initial diagnosis in comparison with corresponding germ line control (saliva samples). The results of WXS were analyzed by Mutect for ranking cancer variants and creating mutational matrix.","abstract":"2014 AML analysis is conducted with samples collected from Chunnam universty. \n67 paired samples are belong to this project.\nThe study was designed to examine the molecular abnormalities from leukemic patients at initial diagnosis in comparison with corresponding germ line control (saliva samples). The results of WXS were analyzed by Mutect for ranking cancer variants and creating mutational matrix.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-12-10T02:04:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001083","title":"LUNG","description":"LUNG","abstract":"LUNG","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001084","title":"Whole exome sequencing reveals the mutational spectrum of testicular germ cell tumours","description":"Testicular germ cell tumours (TGCTs) are the most common cancer in young men. Here we perform whole exome sequencing of 42 TGCTs to comprehensively study the mutational profile of TGCT.  The mutation rate is uniformly low in all of the tumours (mean 0.5 mutations per megabase [Mb]) as compared to the common cancers, consistent with the embryological origin of TGCT. In addition to expected copy number gain of chromosome 12p and mutation of KIT we identify recurrent mutations in the tumour suppressor gene CDC27 (11.9%). Copy number analysis reveals recurring amplification of the spermatocyte development gene FSIP2 (15.3%) and a 0.4Mb region at Xq28 (15.3%). Two treatment-refractory patients are shown to harbour XRCC2 mutations, a gene strongly implicated in defining cisplatin resistance. Our findings provide further insights into genes involved in the development and progression of TGCT.","abstract":"Testicular germ cell tumours (TGCTs) are the most common cancer in young men. Here we perform whole exome sequencing of 42 TGCTs to comprehensively study the mutational profile of TGCT.  The mutation rate is uniformly low in all of the tumours (mean 0.5 mutations per megabase [Mb]) as compared to the common cancers, consistent with the embryological origin of TGCT. In addition to expected copy number gain of chromosome 12p and mutation of KIT we identify recurrent mutations in the tumour suppressor gene CDC27 (11.9%). Copy number analysis reveals recurring amplification of the spermatocyte development gene FSIP2 (15.3%) and a 0.4Mb region at Xq28 (15.3%). Two treatment-refractory patients are shown to harbour XRCC2 mutations, a gene strongly implicated in defining cisplatin resistance. Our findings provide further insights into genes involved in the development and progression of TGCT.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-12-10T11:09:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001085","title":"Capture Hi-C identifies the chromatin interactome of colorectal cancer risk loci","description":"Multiple regulatory elements distant to their targets on the linear genome can influence the expression of a single gene through chromatin looping. Chromosome conformation capture implemented in Hi-C allows for genome-wide agnostic characterization of chromatin contacts. However, detection of functional enhancer-promoter interactions is precluded by its effective resolution that is determined by both restriction fragmentation and sensitivity of the experiment. Here we have developed a capture Hi-C (cHi-C) approach to allow an agnostic characterisation of these physical interactions on a genome-wide scale. Single nucleotide polymorphisms associated with complex diseases often reside within regulatory elements and exert effects through long-range regulation of gene expression. Applying this cHi-C approach to 14 colorectal cancer risk loci has allowed us to identify key long-range chromatin interactions in cis and trans involving these loci.","abstract":"Multiple regulatory elements distant to their targets on the linear genome can influence the expression of a single gene through chromatin looping. Chromosome conformation capture implemented in Hi-C allows for genome-wide agnostic characterization of chromatin contacts. However, detection of functional enhancer-promoter interactions is precluded by its effective resolution that is determined by both restriction fragmentation and sensitivity of the experiment. Here we have developed a capture Hi-C (cHi-C) approach to allow an agnostic characterisation of these physical interactions on a genome-wide scale. Single nucleotide polymorphisms associated with complex diseases often reside within regulatory elements and exert effects through long-range regulation of gene expression. Applying this cHi-C approach to 14 colorectal cancer risk loci has allowed us to identify key long-range chromatin interactions in cis and trans involving these loci.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-12-10T11:24:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001086","title":"Exome_sequencing_of_short_SGA_children_with_IGF_I_and_insulin_resistance","description":"Exome sequencing of short SGA children with IGF-I and insulin resistance. Collaboration with Professor David Dunger, University of Cambridge. Funded by NIHR.","abstract":"Exome sequencing of short SGA children with IGF-I and insulin resistance. Collaboration with Professor David Dunger, University of Cambridge. Funded by NIHR.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-12-10T16:38:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001087","title":"Identification of Somatic Alterations in Stage I Lung Adenocarcinomas by Next-generation Sequencing","description":"Adenocarcinoma is the most common type of lung cancer. Somatic mutations in the early  stage  of  this  disease  have  a  tight  relationship  with  tumor  initiation  and potentially activate downstream pathways that are implicated in tumor progression. In this study, we performed whole genome and exome sequencing of tumor and adjacent normal  tissue  from  10  patients  with  stage  I  lung  adenocarcinoma.  EGFR (4/10 tumors),  BCHE (3/10)  and  TP53 (2/10)  were  identified  recurrently  with  validated tumor-specific  non-synonymous  mutations;  and  the  remaining  mutations  were specific  to  individual  tumors.  Computational  methods  were  used  to  evaluate  the potential effect of non-synonymous mutations on protein function, and putative driver mutation in genes such as SDK1were predicted. Cell adhesion was the most enriched biological  process  in  gene  set  analysis  using  the  DAVID  database.  Copy  number amplification at 12q15, which includes  MDM2, was identified as a recurrent somatic alteration  in  4  of  10  tumors.  These  findings  provided  additional  information  for understanding early-stage lung adenocarcinomas.","abstract":"Adenocarcinoma is the most common type of lung cancer. Somatic mutations in the early  stage  of  this  disease  have  a  tight  relationship  with  tumor  initiation  and potentially activate downstream pathways that are implicated in tumor progression. In this study, we performed whole genome and exome sequencing of tumor and adjacent normal  tissue  from  10  patients  with  stage  I  lung  adenocarcinoma.  EGFR (4/10 tumors),  BCHE (3/10)  and  TP53 (2/10)  were  identified  recurrently  with  validated tumor-specific  non-synonymous  mutations;  and  the  remaining  mutations  were specific  to  individual  tumors.  Computational  methods  were  used  to  evaluate  the potential effect of non-synonymous mutations on protein function, and putative driver mutation in genes such as SDK1were predicted. Cell adhesion was the most enriched biological  process  in  gene  set  analysis  using  the  DAVID  database.  Copy  number amplification at 12q15, which includes  MDM2, was identified as a recurrent somatic alteration  in  4  of  10  tumors.  These  findings  provided  additional  information  for understanding early-stage lung adenocarcinomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001088","title":"Whole-exome analysis reveals special mutation partern in colorectal adenocarcinoma in China","description":"In China, the median age of onset and subsite location of colorectal cancer (CRC) differ greatly to European/American. Disparities of environmental and genetic factors are used to explain such differences. However, no research has been focused on the Chinese CRC genome to elucidate the eastern/western genetic similarities and differences. To gain a comprehensive view of the genetic alterations underlying rectal tumorigenesis in Chinese population, we performed whole-exome analysis of paired 50 colorectal adenocarcinoma tissues from CRC patients in China. Totally, we identified 3126 non-synonymous somatic single nucleotide variations, 72 genes with more than three non-synonymous alterations were discovered in the list, such as APC, KRAS, TP53, FBXW7, PI3KCA, ROBO2, ASTN1, GLI2, ZNF676, SLC12A1, PCDHB3, ASB3, etc. The mutated genes were mainly enriched in the Wnt, MAPK, PI3K, and TGF-b signaling pathways. The functions of partial mutated genes have been investigated and  some of them were revealed to act as potential tumor suppressors whose abnormality may contribute to CRC tumorigenesis.","abstract":"In China, the median age of onset and subsite location of colorectal cancer (CRC) differ greatly to European/American. Disparities of environmental and genetic factors are used to explain such differences. However, no research has been focused on the Chinese CRC genome to elucidate the eastern/western genetic similarities and differences. To gain a comprehensive view of the genetic alterations underlying rectal tumorigenesis in Chinese population, we performed whole-exome analysis of paired 50 colorectal adenocarcinoma tissues from CRC patients in China. Totally, we identified 3126 non-synonymous somatic single nucleotide variations, 72 genes with more than three non-synonymous alterations were discovered in the list, such as APC, KRAS, TP53, FBXW7, PI3KCA, ROBO2, ASTN1, GLI2, ZNF676, SLC12A1, PCDHB3, ASB3, etc. The mutated genes were mainly enriched in the Wnt, MAPK, PI3K, and TGF-b signaling pathways. The functions of partial mutated genes have been investigated and  some of them were revealed to act as potential tumor suppressors whose abnormality may contribute to CRC tumorigenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001089","title":"Russian GWAS of tuberculosis","description":"Genome-wide association study of cases of tuberculosis from St. Petersburg and Samara, in Russia, compared to healthy controls from the same two cities. Genotyped using the Affy6 platform.","abstract":"Genome-wide association study of cases of tuberculosis from St. Petersburg and Samara, in Russia, compared to healthy controls from the same two cities. Genotyped using the Affy6 platform.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001090","title":"GWAS of tuberculosis in Russia","description":"Genome-wide association study of cases of tuberculosis from St Petersburg and Samara, in Russia, compared to healthy controls from the same two cities. Genotype data from Affy6 array.","abstract":"Genome-wide association study of cases of tuberculosis from St Petersburg and Samara, in Russia, compared to healthy controls from the same two cities. Genotype data from Affy6 array.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-12-15T09:28:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001091","title":"GWAS of tuberculosis in Russia","description":"Genome-wide association study of cases of tuberculosis from St Petersburg and Samara, in Russia, compared to healthy controls from the same two cities. Genotype data from Affy6 array.","abstract":"Genome-wide association study of cases of tuberculosis from St Petersburg and Samara, in Russia, compared to healthy controls from the same two cities. Genotype data from Affy6 array.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001092","title":"test","description":"test","abstract":"test","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001093","title":"Exome Sequencing Of 75 Individuals From Multiply Affected Coeliac Families","description":"Coeliac disease is a highly heritable common autoimmune disease involving chronic small intestinal inflammation in response to dietary wheat. The human leukocyte antigen (HLA) region, and 40 newer regions identified by genome wide association studies (GWAS) and dense fine mapping, account for ~40% of the disease heritability. We hypothesized that in pedigrees with multiple individuals with coeliac disease rare [minor allele frequency (MAF)  &lt;0.5%] mutations of larger effect size (odds ratios of ~ 2 – 5) might exist. We sequenced the exomes of 75 coeliac individuals of European ancestry from 55 multiply affected families. We selected interesting variants and genes for further follow up using a combination of: an assessment of shared variants between related subjects, a model-free linkage test, and gene burden tests for multiple, potentially causal, variants. We next performed highly multiplexed amplicon resequencing of all RefSeq exons from 24 candidate genes selected on the basis of the exome sequencing data in 2,248 unrelated coeliac cases and 2,230 controls. 1,335 variants with a 99.9% genotyping call rate were observed in 4,478 samples, of which 939 were present in coding regions of 24 genes (Ti/Tv 2.99). 91.7% of coding variants were rare (MAF &lt;0.5%) and 60% were novel. Gene burden tests performed on rare functional variants identified no significant associations (P&lt;1x10-3) in the resequenced candidate genes. Our strategy of sequencing multiply affected families with deep follow up of candidate genes has not identified any new coeliac disease risk mutations.","abstract":"Coeliac disease is a highly heritable common autoimmune disease involving chronic small intestinal inflammation in response to dietary wheat. The human leukocyte antigen (HLA) region, and 40 newer regions identified by genome wide association studies (GWAS) and dense fine mapping, account for ~40% of the disease heritability. We hypothesized that in pedigrees with multiple individuals with coeliac disease rare [minor allele frequency (MAF)  &lt;0.5%] mutations of larger effect size (odds ratios of ~ 2 – 5) might exist. We sequenced the exomes of 75 coeliac individuals of European ancestry from 55 multiply affected families. We selected interesting variants and genes for further follow up using a combination of: an assessment of shared variants between related subjects, a model-free linkage test, and gene burden tests for multiple, potentially causal, variants. We next performed highly multiplexed amplicon resequencing of all RefSeq exons from 24 candidate genes selected on the basis of the exome sequencing data in 2,248 unrelated coeliac cases and 2,230 controls. 1,335 variants with a 99.9% genotyping call rate were observed in 4,478 samples, of which 939 were present in coding regions of 24 genes (Ti/Tv 2.99). 91.7% of coding variants were rare (MAF &lt;0.5%) and 60% were novel. Gene burden tests performed on rare functional variants identified no significant associations (P&lt;1x10-3) in the resequenced candidate genes. Our strategy of sequencing multiply affected families with deep follow up of candidate genes has not identified any new coeliac disease risk mutations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-12-16T10:11:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001094","title":"Exome and Targeted Resequencing in Coeliac Disease","description":"Coeliac disease is a highly heritable common autoimmune disease involving chronic small intestinal inflammation in response to dietary wheat. The human leukocyte antigen (HLA) region, and 40 newer regions identified by genome wide association studies (GWAS) and dense fine mapping, account for ~40% of the disease heritability. We hypothesized that in pedigrees with multiple individuals with coeliac disease rare [minor allele frequency (MAF)  &lt;0.5%] mutations of larger effect size (odds ratios of ~ 2 – 5) might exist. We sequenced the exomes of 75 coeliac individuals of European ancestry from 55 multiply affected families. We selected interesting variants and genes for further follow up using a combination of: an assessment of shared variants between related subjects, a model-free linkage test, and gene burden tests for multiple, potentially causal, variants. We next performed highly multiplexed amplicon resequencing of all RefSeq exons from 24 candidate genes selected on the basis of the exome sequencing data in 2,248 unrelated coeliac cases and 2,230 controls. 1,335 variants with a 99.9% genotyping call rate were observed in 4,478 samples, of which 939 were present in coding regions of 24 genes (Ti/Tv 2.99). 91.7% of coding variants were rare (MAF &lt;0.5%) and 60% were novel. Gene burden tests performed on rare functional variants identified no significant associations (P&lt;1x10-3) in the resequenced candidate genes. Our strategy of sequencing multiply affected families with deep follow up of candidate genes has not identified any new coeliac disease risk mutations.","abstract":"Coeliac disease is a highly heritable common autoimmune disease involving chronic small intestinal inflammation in response to dietary wheat. The human leukocyte antigen (HLA) region, and 40 newer regions identified by genome wide association studies (GWAS) and dense fine mapping, account for ~40% of the disease heritability. We hypothesized that in pedigrees with multiple individuals with coeliac disease rare [minor allele frequency (MAF)  &lt;0.5%] mutations of larger effect size (odds ratios of ~ 2 – 5) might exist. We sequenced the exomes of 75 coeliac individuals of European ancestry from 55 multiply affected families. We selected interesting variants and genes for further follow up using a combination of: an assessment of shared variants between related subjects, a model-free linkage test, and gene burden tests for multiple, potentially causal, variants. We next performed highly multiplexed amplicon resequencing of all RefSeq exons from 24 candidate genes selected on the basis of the exome sequencing data in 2,248 unrelated coeliac cases and 2,230 controls. 1,335 variants with a 99.9% genotyping call rate were observed in 4,478 samples, of which 939 were present in coding regions of 24 genes (Ti/Tv 2.99). 91.7% of coding variants were rare (MAF &lt;0.5%) and 60% were novel. Gene burden tests performed on rare functional variants identified no significant associations (P&lt;1x10-3) in the resequenced candidate genes. Our strategy of sequencing multiply affected families with deep follow up of candidate genes has not identified any new coeliac disease risk mutations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001095","title":"NGS_based_viability_screening_using_haploid_cell_line","description":"Identification of human deubiquitylating enzymes whose knock out result in hypersensitivity to DNA damaging agents, by comparing the sequence reads of ‘barcode region’ from mixed cell culture.","abstract":"Identification of human deubiquitylating enzymes whose knock out result in hypersensitivity to DNA damaging agents, by comparing the sequence reads of ‘barcode region’ from mixed cell culture.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-12-16T10:32:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001096","title":"Mechanisms_allowing_genetic_and_epigenetic_backgrounds_to_control_cellular_phentypes_of_pancreatic_cells","description":"Human IPSC and ESC lines were differentiated into pancreatic progenitors using the protocoldescribed in Cho C., et al, Diabetologia (2012). Samples were then analysed by ChIPseq ofvarious transcription factors and histone marks, RNAseq, and methylome 450K array. Somesamples will also be submitted for microarray analysis. Information on the lines is availableby managed access for some and open access for othersThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Human IPSC and ESC lines were differentiated into pancreatic progenitors using the protocoldescribed in Cho C., et al, Diabetologia (2012). Samples were then analysed by ChIPseq ofvarious transcription factors and histone marks, RNAseq, and methylome 450K array. Somesamples will also be submitted for microarray analysis. Information on the lines is availableby managed access for some and open access for others","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001097","title":"test","description":"test","abstract":"test","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001098","title":"Compound heterozygous mutations in the noncoding RNU4ATAC gene cause Roifman Syndrome by disrupting minor intron splicing","description":"Roifman Syndrome is a rare congenital disorder characterized by growth retardation, cognitive delay, spondyloepiphyseal dysplasia and antibody deficiency. Given its prevalence in males, it was originally postulated to be X-linked. Whole genome sequencing revealed compound heterozygous rare variants disrupting highly conserved positions of the autosomal non-coding RNU4ATAC gene, a minor spliceosome component essential for minor intron splicing. Targeted sequencing confirmed allele segregation in six cases from four unrelated families. RNU4ATAC has been recently reported to cause Microcephalic osteodysplastic primordial dwarfism, type I (MOPD1), whose phenotype is distinct from Roifman Syndrome. Strikingly, all the six Roifman Syndrome cases have one RNU4ATAC variant overlapping MOPD1-implicated structural elements, while the other variant overlaps a highly conserved element not previously implicated in disease. RNA-seq analysis confirmed defects of minor intron splicing. Available allele frequency data suggests that recessive genetic disorders caused by RNU4ATAC may be more prevalent than reported in the literature.","abstract":"Roifman Syndrome is a rare congenital disorder characterized by growth retardation, cognitive delay, spondyloepiphyseal dysplasia and antibody deficiency. Given its prevalence in males, it was originally postulated to be X-linked. Whole genome sequencing revealed compound heterozygous rare variants disrupting highly conserved positions of the autosomal non-coding RNU4ATAC gene, a minor spliceosome component essential for minor intron splicing. Targeted sequencing confirmed allele segregation in six cases from four unrelated families. RNU4ATAC has been recently reported to cause Microcephalic osteodysplastic primordial dwarfism, type I (MOPD1), whose phenotype is distinct from Roifman Syndrome. Strikingly, all the six Roifman Syndrome cases have one RNU4ATAC variant overlapping MOPD1-implicated structural elements, while the other variant overlaps a highly conserved element not previously implicated in disease. RNA-seq analysis confirmed defects of minor intron splicing. Available allele frequency data suggests that recessive genetic disorders caused by RNU4ATAC may be more prevalent than reported in the literature.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001099","title":"ABIS_1_MeDIP-seq","description":"We investigated changes in whole genome DNA-methylation in a  group of 48 healthy five-year-old children differentiated by their hair cortisol levels. By combining this novel biomarker for chronic stress with methylated DNA immunoprecipitation sequencing (MeDIP-seq), we found that high cortisol were associated with a genome-wide decrease in DNA-methylation targeted to specific zinc finger transcription factor binding sites, repetitive elements and genes important for neurodevelopment and calcium transport. Large scale hypomethylation of repetitive regions, as well as a deficient calcium transport, have been reported in many stress related diseases, as well as in many cancers and biological aging. Thus our findings may aid in our understanding of how susceptibility to these diseases develops.","abstract":"We investigated changes in whole genome DNA-methylation in a  group of 48 healthy five-year-old children differentiated by their hair cortisol levels. By combining this novel biomarker for chronic stress with methylated DNA immunoprecipitation sequencing (MeDIP-seq), we found that high cortisol were associated with a genome-wide decrease in DNA-methylation targeted to specific zinc finger transcription factor binding sites, repetitive elements and genes important for neurodevelopment and calcium transport. Large scale hypomethylation of repetitive regions, as well as a deficient calcium transport, have been reported in many stress related diseases, as well as in many cancers and biological aging. Thus our findings may aid in our understanding of how susceptibility to these diseases develops.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-12-17T19:10:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001100","title":"Colorectal_organoids_and_tumour_tissue___Whole_Genome_X10","description":"Whole genome sequencing of single cell derived organoids from normal colon tissue and colorectal cancer.","abstract":"This study aims to describe mutational processes in colorectal cancer and adjacent normal tissue.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-12-18T09:52:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001101","title":"Modeling of the human alveolar rhabdomyosarcoma Pax3-Foxo1 chromosome translocation in mouse myoblasts using CRISPR-cas9 nuclease","description":"Many recurrent chromosome translocations in cancer result in the generation of fusion genes that are directly implicated in the tumorigenic process. Precise modeling of the effects of cancer fusion genes in mice has been inaccurate as constructs of fusion genes often completely or partially lack the correct regulatory sequences. The reciprocal t(2;13)(q36.1;q14.1) in human alveolar rhabdomyosarcoma (A-RMS) creates a pathognomonic PAX3-FOXO1 fusion gene. In vivo mimicking of this translocation in mice is complicated by the fact that Pax3 and Foxo1 are in opposite orientation on their respective chromosomes, precluding formation of a functional Pax3-Foxo1 fusion via a simple translocation. To circumvent this problem we irreversibly inverted the orientation of a 4.9 Mb syntenic fragment on chromosome 3, encompassing Foxo1, by using Cre-mediated recombination of two pairs of unrelated oppositely oriented LoxP sites situated at the borders of the syntenic region. We tested if spatial proximity of the Pax3 and Foxo1 loci in myoblasts of mice homozygous for the inversion facilitated Pax3-Foxo1 fusion gene formation upon induction of targeted CRISPR-Cas9 nuclease-induced DNA double strand breaks in Pax3 and Foxo1. Fluorescent in situ hybridization indicated that fore limb myoblasts show a higher frequency of Pax3/Foxo1 co-localization than hind limb myoblasts.  Indeed, more fusion genes were generated in fore limb myoblasts via a reciprocal t(1;3), which expressed correctly spliced Pax3-Foxo1 mRNA encoding Pax3-Foxo1 fusion protein. We conclude that locus proximity facilitates chromosome translocation upon induction of DNA double strand breaks. Given that the Pax3-Foxo1 fusion gene will contain all the regulatory sequences necessary for precise regulation of its expression, we propose that CRISPR-Cas9 provides a novel means to faithfully model human diseases caused by chromosome translocation in mice.","abstract":"Many recurrent chromosome translocations in cancer result in the generation of fusion genes that are directly implicated in the tumorigenic process. Precise modeling of the effects of cancer fusion genes in mice has been inaccurate as constructs of fusion genes often completely or partially lack the correct regulatory sequences. The reciprocal t(2;13)(q36.1;q14.1) in human alveolar rhabdomyosarcoma (A-RMS) creates a pathognomonic PAX3-FOXO1 fusion gene. In vivo mimicking of this translocation in mice is complicated by the fact that Pax3 and Foxo1 are in opposite orientation on their respective chromosomes, precluding formation of a functional Pax3-Foxo1 fusion via a simple translocation. To circumvent this problem we irreversibly inverted the orientation of a 4.9 Mb syntenic fragment on chromosome 3, encompassing Foxo1, by using Cre-mediated recombination of two pairs of unrelated oppositely oriented LoxP sites situated at the borders of the syntenic region. We tested if spatial proximity of the Pax3 and Foxo1 loci in myoblasts of mice homozygous for the inversion facilitated Pax3-Foxo1 fusion gene formation upon induction of targeted CRISPR-Cas9 nuclease-induced DNA double strand breaks in Pax3 and Foxo1. Fluorescent in situ hybridization indicated that fore limb myoblasts show a higher frequency of Pax3/Foxo1 co-localization than hind limb myoblasts.  Indeed, more fusion genes were generated in fore limb myoblasts via a reciprocal t(1;3), which expressed correctly spliced Pax3-Foxo1 mRNA encoding Pax3-Foxo1 fusion protein. We conclude that locus proximity facilitates chromosome translocation upon induction of DNA double strand breaks. Given that the Pax3-Foxo1 fusion gene will contain all the regulatory sequences necessary for precise regulation of its expression, we propose that CRISPR-Cas9 provides a novel means to faithfully model human diseases caused by chromosome translocation in mice.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001102","title":"RB Loss in Resistant EGFR Mutant Lung Adenocarcinomas that Transform to Small Cell Lung Cancer","description":"Tyrosine kinase inhibitors (TKIs) are effective treatments for non-small cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) mutations.  However, they do not lead to cures, and, on average, relapse occurs typically occurs afterafter an average of one year of continuous treatment.  In a subset of patients, aA fundamental histological transformation from NSCLC to small cell lung cancer (SCLC) is observed in a subset of the resistant cancers, but the molecular changes associated with this transformation remain unknown. Analysis of a cohort of tumor samples and cell lines derived from resistant EGFR mutant patients with SCLC transformation revealed that RB is lost in 100% of these SCLC transformed cases, but rarely in those that remain NSCLC.  Global changes in gene expression, including increased neuroendocrine marker expression and absence of EGFR expression, are observed in resistant EGFR mutant cancers that transformed to SCLC.  Consistent Further, with their similarities to classical SCLC at the genetic and gene expression levelincreased neuroendocrine marker and decreased EGFR expression as well as greater sensitivity to BCL2 family inhibition are observed in resistant SCLC transformed cancers compared to resistant NSCLCs. , cell lines derived from resistant EGFR mutant SCLC biopsies are substantially more sensitive to Bcl-2 family inhibition with ABT-263 compared to those derived from resistant EGFR mutant NSCLCs.  Together, these findings suggest that despite developing initially as EGFR mutant adenocarcinomas, this subset of resistant cancers ultimately adopt many of the molecular and phenotypic characteristics of classical SCLC.","abstract":"Tyrosine kinase inhibitors (TKIs) are effective treatments for non-small cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) mutations.  However, they do not lead to cures, and, on average, relapse occurs typically occurs afterafter an average of one year of continuous treatment.  In a subset of patients, aA fundamental histological transformation from NSCLC to small cell lung cancer (SCLC) is observed in a subset of the resistant cancers, but the molecular changes associated with this transformation remain unknown. Analysis of a cohort of tumor samples and cell lines derived from resistant EGFR mutant patients with SCLC transformation revealed that RB is lost in 100% of these SCLC transformed cases, but rarely in those that remain NSCLC.  Global changes in gene expression, including increased neuroendocrine marker expression and absence of EGFR expression, are observed in resistant EGFR mutant cancers that transformed to SCLC.  Consistent Further, with their similarities to classical SCLC at the genetic and gene expression levelincreased neuroendocrine marker and decreased EGFR expression as well as greater sensitivity to BCL2 family inhibition are observed in resistant SCLC transformed cancers compared to resistant NSCLCs. , cell lines derived from resistant EGFR mutant SCLC biopsies are substantially more sensitive to Bcl-2 family inhibition with ABT-263 compared to those derived from resistant EGFR mutant NSCLCs.  Together, these findings suggest that despite developing initially as EGFR mutant adenocarcinomas, this subset of resistant cancers ultimately adopt many of the molecular and phenotypic characteristics of classical SCLC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-12-19T16:15:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001103","title":"Whole-exome sequencing of Fanconi anemia","description":"We performed whole-exome sequencing of two Fanconi anemia patients without mutation of known FA genes, and identified a novel FA gene FANCT.","abstract":"We performed whole-exome sequencing of two Fanconi anemia patients without mutation of known FA genes, and identified a novel FA gene FANCT.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2014-12-28T08:43:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001104","title":"We sequenced whole genomes of 12 tumor-blood pairs of nasopharyngeal carcinomas(NPC).","description":"NPC arises from the epithelial of the nasopharynx which has remarkable high prevalence in southern China, southeast Asia and northern Africa. Critical genetic alterations of nasopharyngeal carcinomas remain unclear. We performed whole genome sequencing of 12 tumor-blood pairs to identify the genetics alternation.","abstract":"NPC arises from the epithelial of the nasopharynx which has remarkable high prevalence in southern China, southeast Asia and northern Africa. Critical genetic alterations of nasopharyngeal carcinomas remain unclear. We performed whole genome sequencing of 12 tumor-blood pairs to identify the genetics alternation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001106","title":"Gastric cancers in young patients","description":"Gastric cancers in young patients are aggressive and predominantly of diffuse histology. Also, they are more frequent in female. To identify recurrent somatic alterations in this unique subset of gastric cancers, whole exome and transcriptome analyses were performed using frozen cancer tissue. The same analyses were also performed using adjacent normal tissue (mRNA) or blood (exome) of the same patients.","abstract":"Gastric cancers in young patients are aggressive and predominantly of diffuse histology. Also, they are more frequent in female. To identify recurrent somatic alterations in this unique subset of gastric cancers, whole exome and transcriptome analyses were performed using frozen cancer tissue. The same analyses were also performed using adjacent normal tissue (mRNA) or blood (exome) of the same patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001107","title":"todo","description":"todo","abstract":"todo","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001108","title":"Exome Sequencing Reveals Frequent Inactivating Mutations in BAP1, ARID1A, and PBRM1 in Intrahepatic Cholangiocarcinomas","description":"Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin remodeling genes (including BAP1, ARID1A, and PBRM1) – mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in genes encoding the metabolic enzymes IDH1 and IDH2 in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These studies highlight the importance of dysregulation of chromatin remodeling in intrahepatic cholangiocarcinomas.","abstract":"Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin remodeling genes (including BAP1, ARID1A, and PBRM1) – mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in genes encoding the metabolic enzymes IDH1 and IDH2 in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These studies highlight the importance of dysregulation of chromatin remodeling in intrahepatic cholangiocarcinomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-08T15:49:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001109","title":"Genetic_screening__of_human_stem_cell_differentiation_for_endodermal_cell_lineage","description":"This study will analyse the guide sequence which were used for making mutations in the Cas9-expressing cells. We used GeCKO v2 library which were released by Feng Zhang, 2014. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The goal of this project is to investigate genes regulating definitive endodermal differentiation of human iPSC using genetic screening. The development of definitive endoderm (DE) and its subsequent patterning and differentiation leads to the formation of many of the major organs including the liver, pancreas, lungs, thyroid and intestines. Efficient differentiation to DE is essential for therapeutic purpose, such as transplantation. In recent studies, specific growth factors are used to generate definitive endodermal cells from ESCs including nodal signaling pathway. Although DE differentiation methods using growth factors are useful strategies for generating DE with the ability to differentiate into hepatic or pancreatic lineages, they are not efficient enough for generation of homogenous DE populations. To improve the DE differentiation efficacy, there has been several attempt to find critical genes including transcription factors for DE differentiation. We strongly believe that a more detailed understanding of the molecular pathway of human iPS cell differentiation into DE will help the optimization of differentiation protocol. For this goal, we intend to develop an efficient phenotype-based screening strategy using genome-wide CRISPR gRNA library and deep sequencing to identify genes in DE differentiation. Furthermore, this phenotype-based screening approach can be extended into investigation for further differentiation process like a liver and pancreas progenitors from definitive endodermal cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001110","title":"Blueprint RNAseq profile of purified plasma cells from multiple myeloma patients and tonsils of healthy donors","description":"In the context of an epigenomic study of multiple myeloma, a have generated RNAseq profiles of purified plasma cells from 11 multiple myeloma patients and tonsils of 4 healthy donors","abstract":"In the context of an epigenomic study of multiple myeloma, a have generated RNAseq profiles of purified plasma cells from 11 multiple myeloma patients and tonsils of 4 healthy donors","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-09T15:32:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001111","title":"gdap_wgs","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region.The African Genome Variation Project (AGVP) is an international collaboration that aims to produce a comprehensive catalogue of human genetic variation in SSA. This resource has extended our understanding of population history, patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies.The Genome Diversity in Africa Project (GDAP) will extend and expand the African Genome Variation (AGV) project. Using a sequencing-based approach, GDA project aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out low and high depth whole genome sequencing of up to 2000 individuals across Africa (100 individuals from each ethnolinguistic group), and complement these data with 2.5M Illumina genotyping. We have already completed sequencing of 700 individuals across SSA, we are now adding an additional 540 samples from various ethno-linguistic groups within Africa, including populations from Burkina Faso, Morocco, Ghana, Nigeria, Kenya and South Africa.Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics.","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out low and high depth whole genome sequencing of up to 2000 individuals across Africa (100 individuals from each ethnolinguistic group), and complement these data with 2.5M Illumina genotyping.Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001112","title":"Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers","description":"DNA replication-associated mutations are repaired by two components: polymerase proofreading and mismatch repair. The mutational consequences of disruption to both repair components in humans are not well studied. We sequenced cancer genomes from children with inherited biallelic mismatch repair deficiency (bMMRD). High-grade bMMRD brain tumors exhibited massive numbers of substitution mutations (&gt;250/Mb) – higher than all childhood and most cancers (&gt;7000 analyzed). All ultra-hypermutated bMMRD cancers acquired early somatic driver mutations in DNA polymerases epsilon or delta. The ensuing mutation signatures and numbers are unique and diagnostic of childhood germline bMMRD (p&lt;10e-13). Sequential tumor biopsy analysis revealed that bMMRD/polymerase mutant cancers rapidly amass an excess of simultaneous mutations (~600 mutations/cell division), reaching but not exceeding ~20,000 exonic mutations in &lt;6 months. Thus implying a threshold compatible with cancer cell survival. We suggest a new mechanism of cancer progression in which mutations develop in a rapid burst after ablation of replication repair.","abstract":"DNA replication-associated mutations are repaired by two components: polymerase proofreading and mismatch repair. The mutational consequences of disruption to both repair components in humans are not well studied. We sequenced cancer genomes from children with inherited biallelic mismatch repair deficiency (bMMRD). High-grade bMMRD brain tumors exhibited massive numbers of substitution mutations (&gt;250/Mb) – higher than all childhood and most cancers (&gt;7000 analyzed). All ultra-hypermutated bMMRD cancers acquired early somatic driver mutations in DNA polymerases epsilon or delta. The ensuing mutation signatures and numbers are unique and diagnostic of childhood germline bMMRD (p&lt;10e-13). Sequential tumor biopsy analysis revealed that bMMRD/polymerase mutant cancers rapidly amass an excess of simultaneous mutations (~600 mutations/cell division), reaching but not exceeding ~20,000 exonic mutations in &lt;6 months. Thus implying a threshold compatible with cancer cell survival. We suggest a new mechanism of cancer progression in which mutations develop in a rapid burst after ablation of replication repair.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-12T14:50:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001113","title":"Whole-exome and targeted sequencing of pediatric hyperdiploid B-cell precursor acute lymphoblastic leukemia","description":"High hyperdiploidy defines the largest genetic entity of childhood acute lymphoblastic leukemia (ALL). Despite its relatively low recurrence risk, this subgroup generates a high proportion of relapses. The cause and origin of these relapses remains obscure. We therefore explored the mutational landscape in high hyperdiploid (HD) ALL with whole-exome (n=19) and subsequent targeted deep sequencing of 60 genes in 100 relapsing and 51 non-relapsing cases. We identified multiple clones at diagnosis that were primarily defined by a variety of mutations in receptor tyrosine kinase (RTK)/Ras pathway and chromatin-modifying genes. The relapse clones consisted of reappearing as well as new mutations, and overall contained more mutations. Although RTK/Ras pathway mutations were similarly frequent between diagnosis and relapse, both intergenic and intragenic heterogeneity was essentially lost at relapse. CREBBP mutations, however, increased from initially 18-30% at relapse, then commonly co-occurred with KRAS mutations (P&lt;0.001) and these relapses appeared primarily early (P=0.012). Our results confirm the exceptional susceptibility of HD ALL to RTK/Ras pathway and CREBBP mutations, but, more importantly, suggest that mutant KRAS and CREBBP might cooperate and equip cells with the necessary capacity to evolve into a relapse-generating clone.","abstract":"High hyperdiploidy defines the largest genetic entity of childhood acute lymphoblastic leukemia (ALL). Despite its relatively low recurrence risk, this subgroup generates a high proportion of relapses. The cause and origin of these relapses remains obscure. We therefore explored the mutational landscape in high hyperdiploid (HD) ALL with whole-exome (n=19) and subsequent targeted deep sequencing of 60 genes in 100 relapsing and 51 non-relapsing cases. We identified multiple clones at diagnosis that were primarily defined by a variety of mutations in receptor tyrosine kinase (RTK)/Ras pathway and chromatin-modifying genes. The relapse clones consisted of reappearing as well as new mutations, and overall contained more mutations. Although RTK/Ras pathway mutations were similarly frequent between diagnosis and relapse, both intergenic and intragenic heterogeneity was essentially lost at relapse. CREBBP mutations, however, increased from initially 18-30% at relapse, then commonly co-occurred with KRAS mutations (P&lt;0.001) and these relapses appeared primarily early (P=0.012). Our results confirm the exceptional susceptibility of HD ALL to RTK/Ras pathway and CREBBP mutations, but, more importantly, suggest that mutant KRAS and CREBBP might cooperate and equip cells with the necessary capacity to evolve into a relapse-generating clone.","study_type":"Other","pubmed_ids":[25917266],"external_links":null,"is_released":true,"released_date":"2015-01-13T08:11:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001114","title":"Whole_exome_sequencing_of_additional_thyroid_disease_cases","description":"Whole-exome sequencing of a cohort of families (probands and affected/unaffected relatives) suffering from one of two rare thyroid disorders: congenital hypothyroidism (CH) and resistance to thyroid hormone (RTH).","abstract":"Whole-exome sequencing has been applied successfully to find causal mutations for a number of rare mendelian diseases. Congenital hypothyroidism (CH) and Resistance to Thyroid hormone (RTH) are both rare diseases (affecting less than 1 in 4,000 individuals) for which genetic defects have been identified in a small fraction of cases. The molecular defect underlying most patients is thus still largely unknown. Here we will analyse the exome sequencing of these families, taking into account the pedigree structure and correct mendelian segregation of variants. We will be able to identify not just inherithed but also de novo variants (in trios). We will focus on rare and novel variants that have an impact at the protein level and predict their deleteriousness via commonly used tools. The ultimate aim of the project is the identification of severe candidate variant(s) (possibly in a new gene) that might underlie disease in a given family. These will then be validated and the mechanisms of disease elucidated via functional studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-13T14:48:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001115","title":"Genetic_profiling_of_mucosal_melanoma","description":"Primary mucosal melanomas (MMs) arise from melanocytes located in mucosal membranes lining the respiratory, gastrointestinal and urogenital tracts. MMs frequently present late and have a poor prognosis; the 5-year survival rate is only 14%. MM makes up only ~1.4% of all melanomas and it is this rarity that makes knowledge of the genetic changes that contribute to its pathogenesis limited to a small number of exome/genome studies and other targeted studies. Thus to investigate the somatic alterations and mutation spectra in MM genomes, we have extracted genomic DNA from formalin-fixed, paraffin-embedded (FFPE) human MMs, and subjected them to whole exome sequencing. Given the propensity of MM to metastasize, we will also be sequencing metastatic MM lesions; primary and metastatic lesions from the same individual represent an excellent opportunity to identify potential drivers of metastasis in MM. Finally we will sequence ‘normal’ DNA from the same individual, where possible, to exclude germline variations.","abstract":"Primary mucosal melanomas (MMs) arise from melanocytes located in mucosal membranes lining the respiratory, gastrointestinal and urogenital tracts. MMs frequently present late and have a poor prognosis; the 5-year survival rate is only 14%. MM makes up only ~1.4% of all melanomas and it is this rarity that makes knowledge of the genetic changes that contribute to its pathogenesis limited to a small number of exome/genome studies and other targeted studies. Thus to investigate the somatic alterations and mutation spectra in MM genomes, we have extracted genomic DNA from formalin-fixed, paraffin-embedded (FFPE) human MMs, and subjected them to whole exome sequencing. Given the propensity of MM to metastasize, we will also be sequencing metastatic MM lesions; primary and metastatic lesions from the same individual represent an excellent opportunity to identify potential drivers of metastasis in MM. Finally we will sequence ‘normal’ DNA from the same individual, where possible, to exclude germline variations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-14T08:45:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001116","title":"ESGI___Whole_Genome_Sequencing_of_samples_from_the_Cilentogen_isolates","description":"Deep whole genome sequencing of sampels from the Cilento isolates. The samples are sequenced using the Illumina HiSeq X Ten system.","abstract":"Deep whole genome sequencing of sampels from the Cilento isolates. The samples are sequenced using the Illumina HiSeq X Ten system.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-14T16:55:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001117","title":"ESGI___Whole_Genome_Sequencing_of_NSPHS_samples","description":"Whole genome sequencing of sampels from the NSPHS cohort. The samples are sequenced using the Illumina HiSeq X Ten system.","abstract":"Whole genome sequencing of sampels from the NSPHS cohort. The samples are sequenced using the Illumina HiSeq X Ten system.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-14T17:25:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001118","title":"Genome_Diversity_in_Africa_Project___HLA_diversity","description":"The aim of the project is a comprehensive study of Human Leukocyte Antigen (HLA) diversity in Africa, with an aim of producing resources that will aid future studies. With the information gathered we will produce a reference panel of African HLA haplotypes and surounding genome context. For the pilot phase we will study 125 samples from five populations spread across Africa. These populations should provide an adequate test of our methods in the face of high diversity. As a first step clinical typing of the samples will be performed at Addenbrooke’s Tissue Typing Laboratory.","abstract":"The aim of the project is a comprehensive study of Human Leukocyte Antigen (HLA) diversity in Africa, with an aim of producing resources that will aid future studies. With the information gathered we will produce a reference panel of African HLA haplotypes and surounding genome context.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001119","title":"ESGI___Whole_Genome_Sequencing_of_samples_from_the_Croatian_isolated_populations_","description":"Whole genome sequencing of sampels from isolated populations from Croatia. The samples are sequenced using the Illumina HiSeq X Ten system.","abstract":"Whole genome sequencing of sampels from isolated populations from Croatia. The samples are sequenced using the Illumina HiSeq X Ten system.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-14T17:34:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001120","title":"Genome_Diversity_in_Africa_Project___HLA_diversity","description":"The aim of the project is a comprehensive study of Human Leukocyte Antigen (HLA) diversity in Africa, with an aim of producing resources that will aid future studies. With the information gathered we will produce a reference panel of African HLA haplotypes and surounding genome context. For the pilot phase we will study 125 samples from five populations spread across Africa. These populations should provide an adequate test of our methods in the face of high diversity. As a first step clinical typing of the samples will be performed at Addenbrooke’s Tissue Typing Laboratory.","abstract":"The aim of the project is a comprehensive study of Human Leukocyte Antigen (HLA) diversity in Africa, with an aim of producing resources that will aid future studies. With the information gathered we will produce a reference panel of African HLA haplotypes and surounding genome context.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001121","title":"Genome_Diversity_in_Africa_Project___HLA_diversity","description":"The aim of the project is a comprehensive study of Human Leukocyte Antigen (HLA) diversity in Africa, with an aim of producing resources that will aid future studies. With the information gathered we will produce a reference panel of African HLA haplotypes and surounding genome context. For the pilot phase we will study 125 samples from five populations spread across Africa. These populations should provide an adequate test of our methods in the face of high diversity. As a first step clinical typing of the samples will be performed at Addenbrooke’s Tissue Typing Laboratory.","abstract":"The aim of the project is a comprehensive study of Human Leukocyte Antigen (HLA) diversity in Africa, with an aim of producing resources that will aid future studies. With the information gathered we will produce a reference panel of African HLA haplotypes and surounding genome context.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001122","title":"Genome_Diversity_in_Africa_Project___HLA_diversity","description":"The aim of the project is a comprehensive study of Human Leukocyte Antigen (HLA) diversity in Africa, with an aim of producing resources that will aid future studies. With the information gathered we will produce a reference panel of African HLA haplotypes and surounding genome context. For the pilot phase we will study 125 samples from five populations spread across Africa. These populations should provide an adequate test of our methods in the face of high diversity. As a first step clinical typing of the samples will be performed at Addenbrooke’s Tissue Typing Laboratory.","abstract":"The aim of the project is a comprehensive study of Human Leukocyte Antigen (HLA) diversity in Africa, with an aim of producing resources that will aid future studies. With the information gathered we will produce a reference panel of African HLA haplotypes and surounding genome context.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001123","title":"ESGI___Whole_Genome_Sequencing_of_samples_from_the_INGI_Val_Borbera_genetic_isolate__X10_","description":"Whole genome sequencing of sampels from an isolated population from the Val Borbera valley in Italy. The samples are sequenced using the Illumina HiSeq X Ten system.","abstract":"Whole genome sequencing of sampels from an isolated population from the Val Borbera valley in Italy. The samples are sequenced using the Illumina HiSeq X Ten system.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-14T17:43:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001124","title":"Congenital_anosmia_1","description":"Congenital anosmias can be complete (the lack of a sense of smell) or specific (the inability to detect specific smells). To date, only a single recessive gene underlying complete anosmia has been identified. Here we sequenced the exomes of 10 individuals from a single family, including three with complete anosmia, across three generations to identify the genetic basis of congenital anosmia in this family. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The exomes of 10 individuals from a family with congenital anosmia (three affected, seven unaffected) was sequenced on the Illumina Hiseq platform. The DNA was extracted from a saliva sample.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-14T17:48:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001125","title":"ESGI___Whole_Genome_Sequencing_of_samples_from_the_ORCADES_cohort__X10__","description":"Deep whole genome sequencing of sampels from the Orkney Complex Disease Study (ORCADES), each with data on up to 300 quantitative traits and other risk factors associated with cardiovascular, metabolic and other complex diseases. The samples are sequenced using the Illumina HiSeq X Ten system.","abstract":"Deep whole genome sequencing of sampels from the Orkney Complex Disease Study (ORCADES), each with data on up to 300 quantitative traits and other risk factors associated with cardiovascular, metabolic and other complex diseases. The samples are sequenced using the Illumina HiSeq X Ten system.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-14T17:49:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001126","title":"EBI Submission for mini services testing","description":"Study with affiliated dataset/s for downloading testing","abstract":"Study with affiliated dataset/s for downloading testing","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001127","title":"MiR expression profiles of paired primary colorectal cancerand metastases by next-generation sequencing","description":"MicroRNAs (miRs) have been recognized as promising biomarkers. It is unknown to what extent tumor-derived miRs aredifferentially expressed between primary colorectal cancers (pCRCs) and metastatic lesions, and to what extent the expressionprofiles of tumor tissue differ from the surrounding normal tissue. Next-generation sequencing (NGS) of 220 fresh-frozen samples,including paired primary and metastatic tumor tissue and non-tumorous tissue from 38 patients, revealed expression of 2245known unique mature miRs and 515 novel candidate miRs. Unsupervised clustering of miR expression profiles of pCRC tissue withpaired metastases did not separate the two entities, whereas unsupervised clustering of miR expression profiles of pCRC withnormal colorectal mucosa demonstrated complete separation of the tumor samples from their paired normal mucosa. Twohundred and twenty-two miRs differentiated both pCRC and metastases from normal tissue samples (false discovery rate (FDR)o0.05). The highest expressed tumor-specific miRs were miR-21 and miR-92a, both previously described to be involved in CRC withpotential as circulating biomarker for early detection. Only eight miRs, 0.5% of the analysed miR transcriptome, were differentiallyexpressed between pCRC and the corresponding metastases (FDR o0.1), consisting of five known miRs (miR-320b, miR-320d,miR-3117, miR-1246 and miR-663b) and three novel candidate miRs (chr 1-2552-5p, chr 8-20656-5p and chr 10-25333-3p). Theseresults indicate that previously unrecognized candidate miRs expressed in advanced CRC were identified using NGS. In addition,miR expression profiles of pCRC and metastatic lesions are highly comparable and may be of similar predictive value for prognosisor response to treatment in patients with advanced CRC","abstract":"MicroRNAs (miRs) have been recognized as promising biomarkers. It is unknown to what extent tumor-derived miRs aredifferentially expressed between primary colorectal cancers (pCRCs) and metastatic lesions, and to what extent the expressionprofiles of tumor tissue differ from the surrounding normal tissue. Next-generation sequencing (NGS) of 220 fresh-frozen samples,including paired primary and metastatic tumor tissue and non-tumorous tissue from 38 patients, revealed expression of 2245known unique mature miRs and 515 novel candidate miRs. Unsupervised clustering of miR expression profiles of pCRC tissue withpaired metastases did not separate the two entities, whereas unsupervised clustering of miR expression profiles of pCRC withnormal colorectal mucosa demonstrated complete separation of the tumor samples from their paired normal mucosa. Twohundred and twenty-two miRs differentiated both pCRC and metastases from normal tissue samples (false discovery rate (FDR)o0.05). The highest expressed tumor-specific miRs were miR-21 and miR-92a, both previously described to be involved in CRC withpotential as circulating biomarker for early detection. Only eight miRs, 0.5% of the analysed miR transcriptome, were differentiallyexpressed between pCRC and the corresponding metastases (FDR o0.1), consisting of five known miRs (miR-320b, miR-320d,miR-3117, miR-1246 and miR-663b) and three novel candidate miRs (chr 1-2552-5p, chr 8-20656-5p and chr 10-25333-3p). Theseresults indicate that previously unrecognized candidate miRs expressed in advanced CRC were identified using NGS. In addition,miR expression profiles of pCRC and metastatic lesions are highly comparable and may be of similar predictive value for prognosisor response to treatment in patients with advanced CRC","study_type":"Other","pubmed_ids":[26436952],"external_links":null,"is_released":true,"released_date":"2015-01-19T09:12:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001128","title":"RNA-sequencing of 9 cell-lines and 11 tumour-normal pairs","description":"To investigate these effects in GC, we used next-generation sequencing to determine mRNA populations in 11 gastric adenocarcinomas and matched nonmalignant gastric mucosa samples and in 8 gastric adenocarcinoma cell lines and one normal gastric cell line.","abstract":"To investigate these effects in GC, we used next-generation sequencing to determine mRNA populations in 11 gastric adenocarcinomas and matched nonmalignant gastric mucosa samples and in 8 gastric adenocarcinoma cell lines and one normal gastric cell line.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001129","title":"IBDCA_Edinburgh","description":"In this experiment we have sequenced tumour normal pairs from patients presenting with CRC who have a prior history of inflammatory bowel disease. The idea is to identify driver mutations, new genes and novel pathways associated with the development of these malignancies.","abstract":"In this experiment we have sequenced tumour normal pairs from patients presenting with CRC who have a prior history of inflammatory bowel disease. The idea is to identify driver mutations, new genes and novel pathways associated with the development of these malignancies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-20T13:54:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001130","title":"Genome-wide association study of response to warfarin in a UK prospective cohort","description":"Genome-wide association study of Warfarin dosing in 714 British, recruited in Liverpool and Birmingham. Three phenotypes were investigated: warfarin mean dose, warfarin mean stable dose, and INR over 4 during first week of treatment. Stability was defined by at least three INR measurements within target in a three week period. The samples were genotyped on the Illumina 610K chip and imputed using Impute v2.1, with a combined filtered set composed of HapMap 3 release 2 and 1000 genomes pilot 1 CEU.","abstract":"Genome-wide association study of Warfarin dosing in 714 British, recruited in Liverpool and Birmingham. Three phenotypes were investigated: warfarin mean dose, warfarin mean stable dose, and INR over 4 during first week of treatment. Stability was defined by at least three INR measurements within target in a three week period. The samples were genotyped on the Illumina 610K chip and imputed using Impute v2.1, with a combined filtered set composed of HapMap 3 release 2 and 1000 genomes pilot 1 CEU.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-21T11:19:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001131","title":"Pilot_project_to_evaluate_bowel_preparation_and_sampling_procedure_for_microbiome_studies","description":"We are proposing a pilot to study key factors about endoscopic sampling of the microbiome. These include sampling site, method and the \"bowel preparation\" typically done before endoscopy. Toachieve this we will perform two separate procedures on a small number of IBD patients: onewithout standard bowel preparation, and another follow-up, with prep, a few days later.We plan to collect data from 10 subjects to examine inter-individual variation, and haveplanned for 16 samples per subject:-1 stool sample, for comparison to other published data, mostly stool based-lavage, brushing and biopsy samples from two sites (rectum &amp; left colon) during theunprepared flexible sigmoidoscopy (i.e. the procedure without standard pre-colonoscopicbowel preparation)-lavage, brushing and biopsy samples from three sites (from the rectum, left side of the colonand from the furthest point of intubation - most often the ileum) during the follow-upcolonoscopyDNA will be extracted, and we will perform shotgun metagenomic sequencing on all thesesamples. We can then analyze concordance by site, sampling method and with/without thepreparation. These data will be used to plan our first main microbiome study.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We are proposing a pilot to study key factors about endoscopic sampling of the microbiome. These include sampling site, method and the \"bowel preparation\" typically done before endoscopy. Toachieve this we will perform two separate procedures on a small number of IBD patients: onewithout standard bowel preparation, and another follow-up, with prep, a few days later.We plan to collect data from 10 subjects to examine inter-individual variation, and haveplanned for 16 samples per subject:-1 stool sample, for comparison to other published data, mostly stool based-lavage, brushing and biopsy samples from two sites (rectum &amp; left colon) during theunprepared flexible sigmoidoscopy (i.e. the procedure without standard pre-colonoscopicbowel preparation)-lavage, brushing and biopsy samples from three sites (from the rectum, left side of the colonand from the furthest point of intubation - most often the ileum) during the follow-upcolonoscopyDNA will be extracted, and we will perform shotgun metagenomic sequencing on all thesesamples. We can then analyze concordance by site, sampling method and with/without thepreparation. These data will be used to plan our first main microbiome study.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001132","title":"DPY30_ChIP_seq","description":"H9 human embryonic stem cells (hESCs) were cultured in feeder-free chemically-defined conditions in medium containing 10ng/ml Activin A and 12ng/ml FGF2 (Vallier L. 2011, Methods in Molecular Biology,  690: 57–66). Chromatin immunoprecipitation was performed as described in  Brown S. et al. 2011. Stem Cells 29: 1176–85 by using 5ug of anti-DPY30 antibody (Sigma, cat. number HPA043761). This protocol was performed in control hESCs (expressing a scrambled shRNA) and in hESCs stably expressing an shRNA against DPY30 (Sigma, clone n. TRCN0000131112).This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Activin/Nodal signaling directs the activity of DPY30 to maintain the epigenetic status of humanpluripotent stem cells and their differentiation potential. Human Pluripotent Stem Cells derived from embryos at the blastocyst stage (humanEmbryonic Stem Cells or hESCs) or from reprogrammed somatic cells (human InducedPluripotent Stem Cells or hIPSCs) have the capacity to proliferate indefinitely in vitro whilemaintaining the capacity to differentiate into a broad number of cell types. This uniquepluripotent state is maintained by the Activin/Nodal signalling pathway which controls directlytrough its effectors Smad2/3 the expression of a broad number of factors blockingdifferentiation such as Nanog. In addition, hPSCs are characterised by a specific epigeneticprofile identified by the present of bivalent histone marks on a broad number of genes. Thefunction of these marks is likely to poise developmental genes to be rapidly expressed upondifferentiation and thus this mechanisms has an essential role in the capacity of hPSCs togenerate cell for potential clinical/commercial applications. Importantly, the relation betweenthis specific epigenetic state and the signaling pathways maintening pluripotency such asActivin is not yet understood. To address this limitation, we recently performed coimmunoprecipitationand Mass Spectrometry analyses to identify Smad2/3 partners inhPSCs. These proteomics analyses reveal that Smad2/3 could interact with a broad numberof epigenetic modifiers. Of particular interest, we uncovered that Smad2/3 could interact withDPY30 a core subunit of the SET1/MLL histone methyltransferase complexes whichregulates chromosomal H3K4 trimethylation (H3K4me3) throughout the mammalian genome.We then knocked down and overexpressed DPY30 in hESCs and observed that the resultingphenotype is similar if not identical to the one observed after inhibition of Activin/Nodalsignaling. Indeed, DPY30 appears to be necessary for maintaining the expression ofpluripotency markers and for blocking neuroectoderm markers expression. Moreover, DPY30 expression is required for efficient endoderm differentiation and subsequent specification of hepatic and pancreatic lineages. Importantly, knock-down of DPY30 also resulted in a decrease of H3K4me3 as shown by histone ChIP-QPCR on essential genes such as Nanog or Oct4. Therefore, these studies demonstrated for the firsttime a functional link between an epigenetic modifier complex and the Activin/Nodal signalingin hESCs. However, these observations were performed on limited number of genes and thusonly gave limited information regarding the complexity of the transcriptional networkdownstream DPY30-Smad2/3 complexes. For this reason, we propose to perform DPY30 ChIP-Seq analyses on control and DPY3030 knock down hESCs, to reveal the transcriptional network controlled by DPY30. Overall this study will uncover the mechanisms by which extra-cellular signaling pathways cooperate with  pluripotency factors to orchestrate the activity of epigenetic modifiers and to maintain the pluripotent status of hPSCs.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-22T10:56:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001133","title":"mFAST-SeqS","description":"Recent progress in the analysis of cell-free DNA fragments (cell-free circulating tumor DNA, ctDNA) now allows monitoring of tumor genomes by non-invasive means. However, previous studies with plasma DNA from patients with cancer demonstrated highly variable allele frequencies of ctDNA. The comprehensive analysis of tumor genomes is greatly facilitated when plasma DNA has increased amounts of ctDNA. Therefore, a fast and cost-effective pre-screening method to identify such plasma samples without previous knowledge about alterations in the respective tumor genome could assist in the selection of samples suitable for further extensive qualitative analysis. To address this, we adapted the recently described FAST-SeqS method, which was originally established as a simple and effective, non-invasive screening method for fetal aneuploidy from maternal blood. We show that our modified FAST-SeqS method (mFAST-SeqS) can be used as a pre-screening tool for an estimation of the ctDNA percentage. Using a combined evaluation of genome-wide and chromosome-arm specific z-scores from dilution series with cell line DNA and by comparisons of plasma-Seq profiles with data from mFAST-SeqS, we established a detection limit of 10% or more of mutant alleles. Plasma samples with an mFAST-SeqS z-score above 5 showed highly concordant results compared to copy number profiles obtained from our previously described plasma-Seq approach.","abstract":"Recent progress in the analysis of cell-free DNA fragments (cell-free circulating tumor DNA, ctDNA) now allows monitoring of tumor genomes by non-invasive means. However, previous studies with plasma DNA from patients with cancer demonstrated highly variable allele frequencies of ctDNA. The comprehensive analysis of tumor genomes is greatly facilitated when plasma DNA has increased amounts of ctDNA. Therefore, a fast and cost-effective pre-screening method to identify such plasma samples without previous knowledge about alterations in the respective tumor genome could assist in the selection of samples suitable for further extensive qualitative analysis. To address this, we adapted the recently described FAST-SeqS method, which was originally established as a simple and effective, non-invasive screening method for fetal aneuploidy from maternal blood. We show that our modified FAST-SeqS method (mFAST-SeqS) can be used as a pre-screening tool for an estimation of the ctDNA percentage. Using a combined evaluation of genome-wide and chromosome-arm specific z-scores from dilution series with cell line DNA and by comparisons of plasma-Seq profiles with data from mFAST-SeqS, we established a detection limit of 10% or more of mutant alleles. Plasma samples with an mFAST-SeqS z-score above 5 showed highly concordant results compared to copy number profiles obtained from our previously described plasma-Seq approach.","study_type":"Other","pubmed_ids":[25896989],"external_links":null,"is_released":true,"released_date":"2015-01-22T10:58:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001134","title":"Genome-wide association analysis on five isolated populations - Erasmus Rucphen Family (ERF) Study","description":"ERF is embedded in the Genetic Research in Isolated Population (GRIP) program. Genealogy of GRIP is available from its founding (1600-1650). For ERF, we selected 22 related (first and second degree, non-consanguineous) couples living in GRIP between 1850-1900, and having at least six children baptized in the community church. All living descendants of those couples were invited to participate in ERF1. About 4,000 relatives included in the study form a very complex pedigree, which consists of more than 23,000 members. The participants aged between 18-20 years constitute a unique single family spanning over 23 generations. Around 3,000 individuals have been extensively phenotyped for several psychiatric and somatic traits. All phenotyped individuals are genotyped on genome-wide genotyping arrays.","abstract":"ERF is embedded in the Genetic Research in Isolated Population (GRIP) program. Genealogy of GRIP is available from its founding (1600-1650). For ERF, we selected 22 related (first and second degree, non-consanguineous) couples living in GRIP between 1850-1900, and having at least six children baptized in the community church. All living descendants of those couples were invited to participate in ERF1. About 4,000 relatives included in the study form a very complex pedigree, which consists of more than 23,000 members. The participants aged between 18-20 years constitute a unique single family spanning over 23 generations. Around 3,000 individuals have been extensively phenotyped for several psychiatric and somatic traits. All phenotyped individuals are genotyped on genome-wide genotyping arrays.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-22T12:21:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001135","title":"Intratumor heterogeneity evaluation in primary HCC cells","description":"To investigate Intratumor heterogeneity in HCC and examine the effect of Intratumor heterogeneity on drug response, we collected fresh tissue from multiple tumor regions, representing the spatial extent and macroscopic heterogeneity of the primary tumors. Each region was subjected to primary culture (major part) and HE staining (minor part), the region contained more than 50% tumor cells was went on culture and examine by whole exome sequencing (WES) and CytoScan® HD Array.","abstract":"To investigate Intratumor heterogeneity in HCC and examine the effect of Intratumor heterogeneity on drug response, we collected fresh tissue from multiple tumor regions, representing the spatial extent and macroscopic heterogeneity of the primary tumors. Each region was subjected to primary culture (major part) and HE staining (minor part), the region contained more than 50% tumor cells was went on culture and examine by whole exome sequencing (WES) and CytoScan® HD Array.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-23T10:45:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001136","title":"Microsatellite_Instability_Test","description":"Analysis of colorectal primary tumours to investigate if the mononucleotide repeats which are targeted in the colorectal bait set can be used as a marker for MSI","abstract":"Sequence capture for MSI detection in colorectal cancer","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001137","title":"HipSci___RNAseq___Rare_Monogenic Diabetese","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Monogenic Diabetes. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Monogenic Diabetes. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-26T12:10:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001138","title":"aa","description":"aa","abstract":"aa","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001139","title":"Whole genome and RNA sequencing of paediatric glioblastoma in the ICGC PedBrain project","description":"Paediatric glioblastoma (pedGBM) is characterised by substantial intertumoural heterogeneity. In order to identify the genetic lesions underlying tumourigenesis, we analysed whole genomes and transcriptomes of pedGBMs and in vitro model systems by next generation sequencing. Novel fusions of the receptor tyrosine kinase MET lead us to investigate targeted therapy using MET inhibitors. This study is part of the International Cancer Genome Consortium PedBrain Tumor Project (ICGC PedBrain, http://www.pedbraintumor.org/).","abstract":"Paediatric glioblastoma (pedGBM) is characterised by substantial intertumoural heterogeneity. In order to identify the genetic lesions underlying tumourigenesis, we analysed whole genomes and transcriptomes of pedGBMs and in vitro model systems by next generation sequencing. Novel fusions of the receptor tyrosine kinase MET lead us to investigate targeted therapy using MET inhibitors. This study is part of the International Cancer Genome Consortium PedBrain Tumor Project (ICGC PedBrain, http://www.pedbraintumor.org/).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-26T15:15:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001140","title":"HipSci___Whole_Exome_sequencing___Monogenic_Diabetes","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Monogenic Diabetes.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Monogenic Diabetes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-26T22:11:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001141","title":"Megakaryocyte_production_by_forward_programming_of_human_pluripotent_stem_cells","description":"This project explores human diversity in genetic and epigenetic factors are responsible for high inter-donor variability in production efficiency of megakariocytes from human induced pluripotent cells. We have generated epigenetic signatures in iPSC-derived MKs through a range of genomic technologies including RNAseq, select ChIP for histone modification markers (H3K4me1, H3K27ac and H3K27me3) and methylation sites characterized using Illumina 450k methylation arrays","abstract":"This project explores human diversity in genetic and epigenetic factors are responsible for high inter-donor variability in production efficiency of megakariocytes from human induced pluripotent cells. We have generated epigenetic signatures in iPSC-derived MKs through a range of genomic technologies including RNAseq, select ChIP for histone modification markers (H3K4me1, H3K27ac and H3K27me3) and methylation sites characterized using Illumina 450k methylation arrays","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001142","title":"Defining_epigenetic_changes_in_human_IPS_cells_in_disease_and_in_health_to_identify_mechanisms_for_arrythmogenesis","description":"DNA methylation is a crucial epigenetic modification of the genome that is involved inregulating many cellular processes. These include embryonic development, transcription,chromatin structure, X chromosome inactivation, genomic imprinting and chromosomestability. Consistent with these important roles, a growing number of human diseases havebeen found to be associated with aberrant DNA methylation. The study of these diseases hasprovided new and fundamental insights into the roles that DNA methylation and otherepigenetic modifications have in development and normal cellular homeostasis.However, there is a paucity of data in regards to methylation in complex disorders especiallyin the field of cardiovascular disease, but given the availability of human IPs cells derivationfrom patients one can now go through the differentiation process from inital derivation offibroblasts, to ips cells to terminally differenitated cardiomycytes.To investigate the epigenetic changes in health and disease in a developmental context wehope to use normal and mutant patient fibroblasts for the generation of human Ips cells. Wehope to elucidate the epigentic changes that occur in normal and in mutant ips lines within afamily to couple our transcritional changes found in the mutants to have a better mechanisticunderstanding of arrhythmogenesis.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"DNA methylation is a crucial epigenetic modification of the genome that is involved inregulating many cellular processes. These include embryonic development, transcription,chromatin structure, X chromosome inactivation, genomic imprinting and chromosomestability. Consistent with these important roles, a growing number of human diseases havebeen found to be associated with aberrant DNA methylation. The study of these diseases hasprovided new and fundamental insights into the roles that DNA methylation and otherepigenetic modifications have in development and normal cellular homeostasis.However, there is a paucity of data in regards to methylation in complex disorders especiallyin the field of cardiovascular disease, but given the availability of human IPs cells derivationfrom patients one can now go through the differentiation process from inital derivation offibroblasts, to ips cells to terminally differenitated cardiomycytes.To investigate the epigenetic changes in health and disease in a developmental context wehope to use normal and mutant patient fibroblasts for the generation of human Ips cells. Wehope to elucidate the epigentic changes that occur in normal and in mutant ips lines within afamily to couple our transcritional changes found in the mutants to have a better mechanisticunderstanding of arrhythmogenesis.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001143","title":"Extension_of_DDD_GWAS_data","description":"Pathogenic variants in over 1,000 genes can cause diverse developmental disorders (DDs)as a result of perturbed embryonic development, and yet the high proportion of patientswithout a genetic diagnosis suggest that many more genetic causes remain undiscovered.The common variant burden for these disorder remains unknown, despite clear evidence thatsimilar neurodevelopmental disorders (e.g. autism) are substantially influenced by commonvariants. We therefore produced GWAS data on 4000 children with developmental disorders.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Pathogenic variants in over 1,000 genes can cause diverse developmental disorders (DDs)as a result of perturbed embryonic development, and yet the high proportion of patientswithout a genetic diagnosis suggest that many more genetic causes remain undiscovered.The common variant burden for these disorder remains unknown, despite clear evidence thatsimilar neurodevelopmental disorders (e.g. autism) are substantially influenced by commonvariants. We therefore produced GWAS data on 4000 children with developmental disorders.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001144","title":"bb","description":"bb","abstract":"bb","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001145","title":"FWO_project_G_0687_12_X10_WGS","description":"Profiling subclonal architecture and phylogeny in tumors by whole-genome sequence data mining and single-cell genome sequencing","abstract":"Profiling subclonal architecture and phylogeny in tumors by whole-genome sequence data mining and single-cell genome sequencing","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-01-29T08:51:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001146","title":"Efficacy of JAK/STAT pathway inhibition in murine xenograft models of early T-cell precursor (ETP) acute lymphoblastic leukemia","description":"Early T-cell precursor (ETP) acute lymphoblastic leukemia (ALL) is a recently described subtype of T-ALL characterized by a unique immunophenotype and genomic profile as well as a high rate of induction failure. Frequent mutations in cytokine receptor and JAK/STAT signaling pathways led us to hypothesize that ETP-ALL is dependent on JAK/STAT signaling. Here we demonstrate aberrant activation of the JAK/STAT pathway in ETP-ALL blasts relative to non-ETP T-ALL. Moreover, ETP-ALL showed hyperactivation of STAT5 in response to IL7, an effect that was abrogated by the JAK1/2 inhibitor ruxolitinib. In vivo, ruxolitinib displayed activity in 6/6 patient-derived murine xenograft models of ETP-ALL, with profound single-agent efficacy in 5 models. Ruxolitinib treatment decreased peripheral blast counts relative to pre-treatment levels and compared to control (P&lt;0.01) in 5/6 ETP-ALL xenografts, with marked reduction in mean splenic blast counts (P&lt;0.01) in 6/6 samples. Surprisingly, both JAK/STAT pathway activation and ruxolitinib efficacy were independent of the presence of JAK/STAT pathway mutations, raising the possibility that the therapeutic potential of ruxolitinib in ETP-ALL extends beyond those cases with JAK mutations. These findings establish the preclinical in vivo efficacy of ruxolitinib in ETP-ALL, a biologically distinct subtype for which novel therapies are needed.","abstract":"Early T-cell precursor (ETP) acute lymphoblastic leukemia (ALL) is a recently described subtype of T-ALL characterized by a unique immunophenotype and genomic profile as well as a high rate of induction failure. Frequent mutations in cytokine receptor and JAK/STAT signaling pathways led us to hypothesize that ETP-ALL is dependent on JAK/STAT signaling. Here we demonstrate aberrant activation of the JAK/STAT pathway in ETP-ALL blasts relative to non-ETP T-ALL. Moreover, ETP-ALL showed hyperactivation of STAT5 in response to IL7, an effect that was abrogated by the JAK1/2 inhibitor ruxolitinib. In vivo, ruxolitinib displayed activity in 6/6 patient-derived murine xenograft models of ETP-ALL, with profound single-agent efficacy in 5 models. Ruxolitinib treatment decreased peripheral blast counts relative to pre-treatment levels and compared to control (P&lt;0.01) in 5/6 ETP-ALL xenografts, with marked reduction in mean splenic blast counts (P&lt;0.01) in 6/6 samples. Surprisingly, both JAK/STAT pathway activation and ruxolitinib efficacy were independent of the presence of JAK/STAT pathway mutations, raising the possibility that the therapeutic potential of ruxolitinib in ETP-ALL extends beyond those cases with JAK mutations. These findings establish the preclinical in vivo efficacy of ruxolitinib in ETP-ALL, a biologically distinct subtype for which novel therapies are needed.","study_type":"Other","pubmed_ids":[25645356],"external_links":null,"is_released":true,"released_date":"2015-01-30T18:30:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001147","title":"463 newly diagnosed patients with Multiple Myeloma underwent whole exome sequencing of tumour and peripheral blood DNA.","description":"463 newly diagnosed patients from the UK Myeloma XI clinical trial (NCT01554852) underwent whole exome sequencing plus targeted capture of the IGH/K/L and MYC loci.  200 ng of DNA were processed using NEBNext DNA library prepartion kit and hybridised to the SureSelect Human All Exon V5 Plus.  Four samples were pooled and run on one lane of a HiSeq 2000 using 76-bp paired end reads.  DNA from CD138+ selected bone marrow cells (myeloma tumour) as well as peripheral white blood cells were analysed and somatic mutations detected.","abstract":"463 newly diagnosed patients from the UK Myeloma XI clinical trial (NCT01554852) underwent whole exome sequencing plus targeted capture of the IGH/K/L and MYC loci.  200 ng of DNA were processed using NEBNext DNA library prepartion kit and hybridised to the SureSelect Human All Exon V5 Plus.  Four samples were pooled and run on one lane of a HiSeq 2000 using 76-bp paired end reads.  DNA from CD138+ selected bone marrow cells (myeloma tumour) as well as peripheral white blood cells were analysed and somatic mutations detected.","study_type":"Other","pubmed_ids":[25904160],"external_links":null,"is_released":true,"released_date":"2015-02-02T11:49:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001148","title":"A personalised medicine approach for ponatinib-resistant chronic myeloid leukaemia","description":"Chronic myeloid leukaemia (CML) is characterised by the presence of a fusion driver oncogene, BCR-ABL1, which is a constitutive tyrosine kinase. Tyrosine kinase inhibitors (TKIs) are the central treatment strategy for CML patients and have significantly improved survival rates, but the T315I mutation in the kinase domain of BCR-ABL1 confers resistance to all clinically approved TKIs, except ponatinib. However, compound mutations can mediate resistance even to ponatinib and remain a clinical challenge in CML therapy. Here, we investigated a ponatinib-resistant CML patient through whole genome sequencing (WGS) to identify the cause of resistance and to find alternative therapeutic targets.","abstract":"Chronic myeloid leukaemia (CML) is characterised by the presence of a fusion driver oncogene, BCR-ABL1, which is a constitutive tyrosine kinase. Tyrosine kinase inhibitors (TKIs) are the central treatment strategy for CML patients and have significantly improved survival rates, but the T315I mutation in the kinase domain of BCR-ABL1 confers resistance to all clinically approved TKIs, except ponatinib. However, compound mutations can mediate resistance even to ponatinib and remain a clinical challenge in CML therapy. Here, we investigated a ponatinib-resistant CML patient through whole genome sequencing (WGS) to identify the cause of resistance and to find alternative therapeutic targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001149","title":"Mapping_regulatory_variation_in_sensory_neurons_using_IPS_lines_from_the_HIPSCI_project","description":"Sensory neurons are nerve cells that are activated by sensory input such as heat, light and convey information to the brain. Although a key cell type in complex organisms, human sensory neurons are challenging to study because they are impossible to obtain from living donors. We have collaborated with the Neucentis Pharmaceutical Research Unit to differentiate sensory neuron like cells from human induced pluripotent stem cells  derived as part of the Human Induced Pluripotent Stem Cells Initiative. We will sequence RNA from 100 IPS lines derived from healthy individuals and perform RNA-seq on the differentiated cells to identify noncoding variants that alter gene expression in human sensory neurons.","abstract":"Sensory neurons are nerve cells that are activated by sensory input such as heat, light and convey information to the brain. Although a key cell type in complex organisms, human sensory neurons are challenging to study because they are impossible to obtain from living donors. We have collaborated with the Neucentis Pharmaceutical Research Unit to differentiate sensory neuron like cells from human induced pluripotent stem cells  derived as part of the Human Induced Pluripotent Stem Cells Initiative. We will sequence RNA from 100 IPS lines derived from healthy individuals and perform RNA-seq on the differentiated cells to identify noncoding variants that alter gene expression in human sensory neurons.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-02-05T13:46:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001150","title":"A personalised medicine approach for ponatinib-resistant chronic myeloid leukaemia","description":"Chronic myeloid leukaemia (CML) is characterised by the presence of a fusion driver oncogene, BCR-ABL1, which is a constitutive tyrosine kinase. Tyrosine kinase inhibitors (TKIs) are the central treatment strategy for CML patients and have significantly improved survival rates, but the T315I mutation in the kinase domain of BCR-ABL1 confers resistance to all clinically approved TKIs, except ponatinib. However, compound mutations can mediate resistance even to ponatinib and remain a clinical challenge in CML therapy. Here, we investigated a ponatinib-resistant CML patient through whole genome sequencing (WGS) to identify the cause of resistance and to find alternative therapeutic targets.","abstract":"Chronic myeloid leukaemia (CML) is characterised by the presence of a fusion driver oncogene, BCR-ABL1, which is a constitutive tyrosine kinase. Tyrosine kinase inhibitors (TKIs) are the central treatment strategy for CML patients and have significantly improved survival rates, but the T315I mutation in the kinase domain of BCR-ABL1 confers resistance to all clinically approved TKIs, except ponatinib. However, compound mutations can mediate resistance even to ponatinib and remain a clinical challenge in CML therapy. Here, we investigated a ponatinib-resistant CML patient through whole genome sequencing (WGS) to identify the cause of resistance and to find alternative therapeutic targets.","study_type":"Other","pubmed_ids":[25712455],"external_links":null,"is_released":true,"released_date":"2015-02-05T15:41:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001151","title":"Identifying autosomal recessive mutations causing neurological disorders","description":"The objective of this study is to resequence of targeted intervals containing autosomal recessive variants causing neurological disorders in consanguineous pedigrees. Using homozygosity mapping, three intervals of very different sizes have previously been unambiguously mapped for three different neurological diseases: 2.4Mb, 8Mb and 14.3Mb in size, for Microlissencephaly, Severe Mental Retardation and Complicated hereditary spastic paraplegia respectively. This study is a pilot to assess how well custom targeted resequencing performs across a broad size range of intervals. The study design is to use a different custom capture probe set for each interval, pulldown from a single patient from each family, and sequence 1 lane using Illumina single-reads for each sample. Candidate variants will be followed up in the families themselves, and in patients with similar phenotypes from outbred populations","abstract":"The objective of this study is to resequence of targeted intervals containing autosomal recessive variants causing neurological disorders in consanguineous pedigrees. Using homozygosity mapping, three intervals of very different sizes have previously been unambiguously mapped for three different neurological diseases: 2.4Mb, 8Mb and 14.3Mb in size, for Microlissencephaly, Severe Mental Retardation and Complicated hereditary spastic paraplegia respectively. This study is a pilot to assess how well custom targeted resequencing performs across a broad size range of intervals. The study design is to use a different custom capture probe set for each interval, pulldown from a single patient from each family, and sequence 1 lane using Illumina single-reads for each sample. Candidate variants will be followed up in the families themselves, and in patients with similar phenotypes from outbred populations","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001152","title":"Identifying autosomal recessive mutations causing neurological disorders","description":"The objective of this study is to resequence of targeted intervals containing autosomal recessive variants causing neurological disorders in consanguineous pedigrees. Using homozygosity mapping, three intervals of very different sizes have previously been unambiguously mapped for three different neurological diseases: 2.4Mb, 8Mb and 14.3Mb in size, for Microlissencephaly, Severe Mental Retardation and Complicated hereditary spastic paraplegia respectively. This study is a pilot to assess how well custom targeted resequencing performs across a broad size range of intervals. The study design is to use a different custom capture probe set for each interval, pulldown from a single patient from each family, and sequence 1 lane using Illumina paired-reads for each sample. Candidate variants will be followed up in the families themselves, and in patients with similar phenotypes from outbred populations","abstract":"The objective of this study is to resequence of targeted intervals containing autosomal recessive variants causing neurological disorders in consanguineous pedigrees. Using homozygosity mapping, three intervals of very different sizes have previously been unambiguously mapped for three different neurological diseases: 2.4Mb, 8Mb and 14.3Mb in size, for Microlissencephaly, Severe Mental Retardation and Complicated hereditary spastic paraplegia respectively. This study is a pilot to assess how well custom targeted resequencing performs across a broad size range of intervals. The study design is to use a different custom capture probe set for each interval, pulldown from a single patient from each family, and sequence 1 lane using Illumina paired-reads for each sample. Candidate variants will be followed up in the families themselves, and in patients with similar phenotypes from outbred populations","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001153","title":"Aplastic anemia","description":"Clonal hematopoiesis was investigated in patients with aplastic anemia using next-generation sequencing and single-nucleotide polymorphism (SNP) array-based karyotyping.","abstract":"Clonal hematopoiesis was investigated in patients with aplastic anemia using next-generation sequencing and single-nucleotide polymorphism (SNP) array-based karyotyping.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-02-10T19:46:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001154","title":"Genome-wide association study of JAK2 V617F negative myeloproliferative neoplasms (MPN)","description":"Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL but the contribution of inherited factors is poorly characterized. Using a genome-wide association study of MPN cases and controls, we identify two SNPs with genome-wide significance in JAK2 V617F negative MPN: rs12339666 (JAK2;  meta-analysis P=1.27x10-10) and rs2201862 (MECOM; meta-analysis P=1.96x10-9). Two additional SNPs, rs2736100 (TERT) and rs9376092 (HBS1L/MYB) achieve genome-wide significance when including JAK2V617F positive cases. rs9376092 has a stronger effect in JAK2V617F negative cases with CALR and/or MPL mutations (Breslow-Day P=4.5x10-7) whereas in JAK2V617F positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic chi-square P=7.3x10-7). Reduced MYB expression, previously linked to development of an ET-like disease in model systems, associates with rs9376092 in normal myeloid cells. These findings demonstrate that multiple germline variants predispose to MPN and link constitutional differences in MYB expression to disease phenotype.","abstract":"Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL but the contribution of inherited factors is poorly characterized. Using a genome-wide association study of MPN cases and controls, we identify two SNPs with genome-wide significance in JAK2 V617F negative MPN: rs12339666 (JAK2;  meta-analysis P=1.27x10-10) and rs2201862 (MECOM; meta-analysis P=1.96x10-9). Two additional SNPs, rs2736100 (TERT) and rs9376092 (HBS1L/MYB) achieve genome-wide significance when including JAK2V617F positive cases. rs9376092 has a stronger effect in JAK2V617F negative cases with CALR and/or MPL mutations (Breslow-Day P=4.5x10-7) whereas in JAK2V617F positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic chi-square P=7.3x10-7). Reduced MYB expression, previously linked to development of an ET-like disease in model systems, associates with rs9376092 in normal myeloid cells. These findings demonstrate that multiple germline variants predispose to MPN and link constitutional differences in MYB expression to disease phenotype.","study_type":"Other","pubmed_ids":[0],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001155","title":"Anaplastic_Meningioma_V3__cancer_gene_panel","description":"Investigation into causal genes underlying anaplastic meningioma","abstract":"Investigation into causal genes underlying anaplastic meningioma","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-02-11T17:10:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001156","title":"Genetic association between the seleted SNP, circulating levels of the metabolite and body composition in UK twins","description":"The contribution of specific molecular-genetic factors to muscle mass variation and sarcopenia remains largely unknown. To identify endogenous molecules and specific genetic factors associated with appendicular lean mass (APLM) in the general population, cross-sectional data from the TwinsUK Adult Twin Registry was used. Non-targeted mass spec-based metabolomic profiling was performed on plasma of 3953 females (mostly dizygotic and monozygotic twins). APLM was measured using dual-energy X-ray absorptiometry (DXA) and genotyping was genome-wide (GWAS). Specific metabolites were used as intermediate phenotypes in the identification of single nucleotide polymorphisms associated with APLM using GWAS. 162 metabolites were found significantly correlated with APLM, and explained 17.4% of its variation. However, the top three of them (unidentified substance X12063, urate and mannose) explained 11.1% (p≤9.25*10-26) so each was subjected to GWAS. Each metabolite showed highly significant (p≤9.28*10-46) associations with genetic variants in the corresponding genomic regions. Mendelian randomization using these SNPs found no evidence for a direct causal effect of these metabolites on APLM. However, using a new software platform for bivariate analysis we showed that shared genetic factors contribute significantly (p≤4.31*10-43) to variance in both the metabolites and APLM - independent of the effect of the associated SNPs. There are several metabolites, having a clear pattern of genetic inheritance, which are highly significantly associated with APLM and may provide a cheap and readily accessible biomarker of muscle mass. However, the mechanism by which the genetic factor influences muscle mass remains to be discovered.","abstract":"The contribution of specific molecular-genetic factors to muscle mass variation and sarcopenia remains largely unknown. To identify endogenous molecules and specific genetic factors associated with appendicular lean mass (APLM) in the general population, cross-sectional data from the TwinsUK Adult Twin Registry was used. Non-targeted mass spec-based metabolomic profiling was performed on plasma of 3953 females (mostly dizygotic and monozygotic twins). APLM was measured using dual-energy X-ray absorptiometry (DXA) and genotyping was genome-wide (GWAS). Specific metabolites were used as intermediate phenotypes in the identification of single nucleotide polymorphisms associated with APLM using GWAS. 162 metabolites were found significantly correlated with APLM, and explained 17.4% of its variation. However, the top three of them (unidentified substance X12063, urate and mannose) explained 11.1% (p≤9.25*10-26) so each was subjected to GWAS. Each metabolite showed highly significant (p≤9.28*10-46) associations with genetic variants in the corresponding genomic regions. Mendelian randomization using these SNPs found no evidence for a direct causal effect of these metabolites on APLM. However, using a new software platform for bivariate analysis we showed that shared genetic factors contribute significantly (p≤4.31*10-43) to variance in both the metabolites and APLM - independent of the effect of the associated SNPs. There are several metabolites, having a clear pattern of genetic inheritance, which are highly significantly associated with APLM and may provide a cheap and readily accessible biomarker of muscle mass. However, the mechanism by which the genetic factor influences muscle mass remains to be discovered.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001157","title":"Edit_FFPE_Normal_Panel_V1_Colorectal_Panel","description":"FFPE normal panel generation for use with colorectal bait design 0708951","abstract":"FFPE normal panel generation for use with colorectal bait design 0708951","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001158","title":"Leeds_Melanoma_Cohort","description":"Leeds Melanoma Cohort","abstract":"Malignant melanoma is a cancer that upon the development of metastatic disease has a dismal prognosis, despite the recent evelopment of therapeutic agents that target driver mutations. The mutational landscape of melanoma has been well described for metastatic lesions (Hodis et al, 2012) but is much less well characterised for early stage primary lesions. These tend to be small lesions where technical challenges such as DNA quantity and formaldehyde-fixation are important issues. We will test our ability to sequence such samples against a panel of approx. 360 genes. If successful, we will extend this study to a much larger cohort.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-02-12T14:24:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001159","title":"The BC Cancer Agency's Personalized Onco-Genomics Project","description":"The BC Cancer Agency's Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","abstract":"The BC Cancer Agency's Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-02-19T15:19:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001162","title":"Pilot study of 10 ID patient-parent trios WES","description":"Pilot study of 10 patients with intellectual disability, family-based-whole-exome sequencing in trio.","abstract":"Pilot study of 10 patients with intellectual disability, family-based-whole-exome sequencing in trio.","study_type":"Other","pubmed_ids":[24531329,25081361],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001164","title":"Pilot Study of 10 patients with ID, WES trios.","description":"Pilot study of 10 patients with intellectual disability using family-based-whole-exome sequencing (patient-paertn trios).","abstract":"Pilot study of 10 patients with intellectual disability using family-based-whole-exome sequencing (patient-paertn trios).","study_type":"Other","pubmed_ids":[24531329,25081361],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001165","title":"Genesis of Two Most Prevalent Variants Causing Combined Pituitary Hormone Deficiency in 21 Populations","description":"Two variants (c.[301_302delAG];[301_302delAG] and c.[150delA];[150delA]) in the PROP1 gene are the most common genetic causes of recessively inherited combined pituitary hormones deficiency (CPHD). Our objective was to analyze in detail the origin of the two most prevalent variants. In the multicentric study were included 237 patients with CPHD and their 15 relatives carrying c.[301_302delAG];[301_302delAG] or c.[150delA];[150delA] or c.[301_302delAG];[ 150delA]. They originated from 21 different countries worldwide. We genotyped 21 single nucleotide variant markers flanking the 9.6Mb region around the PROP1 gene that are not in mutual linkage disequilibrium in the general populations - a finding of a common haplotype would be indicative of ancestral origin of the variant. Haplotypes were reconstructed by Phase and Haploview software, and the variant age was estimated using an allelic association method. We demonstrated ancestral origin of both variants: c.[301_302delAG] was carried on 0.2Mb-long haplotype in a majority of European patients arising approximately 101 generations ago (confidence interval 90.1-116.4). Patients from the Iberian Peninsula displayed a different haplotype which was estimated to have emerged 23.3 (20.1-29.1) generations ago. Subsequently, the data indicated that both haplotypes were transmitted to Latin American patients approximately 13.8 (12.2-17.0) and 16.4 (14.4-20.1) generations ago, respectively. The c.[150delA] variant that was carried on a haplotype spanning about 0.3Mb was estimated to appear 43.7 (38.4-52.7) generations ago. We present strong evidence that the most frequent variants in the PROP1 gene are not a consequence of variant hot-spots as previously assumed, but are founder variants.","abstract":"Two variants (c.[301_302delAG];[301_302delAG] and c.[150delA];[150delA]) in the PROP1 gene are the most common genetic causes of recessively inherited combined pituitary hormones deficiency (CPHD). Our objective was to analyze in detail the origin of the two most prevalent variants. In the multicentric study were included 237 patients with CPHD and their 15 relatives carrying c.[301_302delAG];[301_302delAG] or c.[150delA];[150delA] or c.[301_302delAG];[ 150delA]. They originated from 21 different countries worldwide. We genotyped 21 single nucleotide variant markers flanking the 9.6Mb region around the PROP1 gene that are not in mutual linkage disequilibrium in the general populations - a finding of a common haplotype would be indicative of ancestral origin of the variant. Haplotypes were reconstructed by Phase and Haploview software, and the variant age was estimated using an allelic association method. We demonstrated ancestral origin of both variants: c.[301_302delAG] was carried on 0.2Mb-long haplotype in a majority of European patients arising approximately 101 generations ago (confidence interval 90.1-116.4). Patients from the Iberian Peninsula displayed a different haplotype which was estimated to have emerged 23.3 (20.1-29.1) generations ago. Subsequently, the data indicated that both haplotypes were transmitted to Latin American patients approximately 13.8 (12.2-17.0) and 16.4 (14.4-20.1) generations ago, respectively. The c.[150delA] variant that was carried on a haplotype spanning about 0.3Mb was estimated to appear 43.7 (38.4-52.7) generations ago. We present strong evidence that the most frequent variants in the PROP1 gene are not a consequence of variant hot-spots as previously assumed, but are founder variants.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-02-19T15:17:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001167","title":"The Berlin (BLN) panel of glioblastoma cell lines: RNAseq of human gliomasphere cell lines and matched parental tumors","description":"We generated a panel of nine glioma stem-like cell lines under serum-free cell culture conditions from human glioblastoma samples. In addition to clinical annotation, MR imaging and histological characterization of the parental tumor, as well as xenograft studies of tumorigenecity, transcriptomic profiling of tumor/cell line pairs by RNA sequencing has been performed.","abstract":"We generated a panel of nine glioma stem-like cell lines under serum-free cell culture conditions from human glioblastoma samples. In addition to clinical annotation, MR imaging and histological characterization of the parental tumor, as well as xenograft studies of tumorigenecity, transcriptomic profiling of tumor/cell line pairs by RNA sequencing has been performed.","study_type":"Other","pubmed_ids":[28148826],"external_links":null,"is_released":true,"released_date":"2015-02-19T14:44:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001168","title":"GWAS study on arsenic-exposed population","description":"Genetic analysis of women from the Andes Mountains that are exposed to arsenic in drinking water.","abstract":"Genetic analysis of women from the Andes Mountains that are exposed to arsenic in drinking water.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-02-20T10:00:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001169","title":"27 libraries representing 11 different combinations of caste, gender, developmental stage. 50 base pair single-end reads generated on three lanes of an Illumina HiSeq 2500 system in rapid mode.","description":"Reproductive workers show queen-like gene expression in an intermediately eusocial insect, the buff-tailed bumble bee Bombus terrestris.  Bumble bees represent a taxon with an intermediate level of eusociality within Hymenoptera. The clear division of reproduction between a single founding queen and the largely sterile workers is characteristic for highly eusocial species, whereas the morphological similarity between the bumble bee queen and the workers is typical for more primitively eusocial hymenopterans. Also, unlike other highly eusocial hymenopterans, division of labour among worker sub-castes is plastic and not predetermined by morphology or age. We conducted a differential expression analysis based on RNA-seq data from 11 combinations of developmental stage and caste to investigate how a single genome can produce the distinct castes of queens, workers and males in the buff-tailed bumble bee Bombus terrestris. Based on expression patterns, we found males to be the most distinct of all adult castes (2,411 transcripts differentially expressed compared to non-reproductive workers). However, only relatively few transcripts were differentially expressed between males and workers during development (larvae: 71, pupae: 162). This indicates the need for more distinct expression patterns to control behaviour and physiology in adults compared to those required to create different morphologies. Among the female castes, the expression of over ten times more transcripts differed significantly between reproductive workers and their non-reproductive sisters than when comparing reproductive workers to the mother queen. This suggests a strong shift towards a more queen-like behaviour and physiology when a worker becomes fertile. This is in contrast to findings for higher eusocial species, in which reproductive workers are more similar to non-reproductive workers than the queen.","abstract":"Reproductive workers show queen-like gene expression in an intermediately eusocial insect, the buff-tailed bumble bee Bombus terrestris.  Bumble bees represent a taxon with an intermediate level of eusociality within Hymenoptera. The clear division of reproduction between a single founding queen and the largely sterile workers is characteristic for highly eusocial species, whereas the morphological similarity between the bumble bee queen and the workers is typical for more primitively eusocial hymenopterans. Also, unlike other highly eusocial hymenopterans, division of labour among worker sub-castes is plastic and not predetermined by morphology or age. We conducted a differential expression analysis based on RNA-seq data from 11 combinations of developmental stage and caste to investigate how a single genome can produce the distinct castes of queens, workers and males in the buff-tailed bumble bee Bombus terrestris. Based on expression patterns, we found males to be the most distinct of all adult castes (2,411 transcripts differentially expressed compared to non-reproductive workers). However, only relatively few transcripts were differentially expressed between males and workers during development (larvae: 71, pupae: 162). This indicates the need for more distinct expression patterns to control behaviour and physiology in adults compared to those required to create different morphologies. Among the female castes, the expression of over ten times more transcripts differed significantly between reproductive workers and their non-reproductive sisters than when comparing reproductive workers to the mother queen. This suggests a strong shift towards a more queen-like behaviour and physiology when a worker becomes fertile. This is in contrast to findings for higher eusocial species, in which reproductive workers are more similar to non-reproductive workers than the queen.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001170","title":"Recursive splicing in long vertebrate genes","description":"Recent studies have shown that expression of many genes with exceptionally long introns in the mammalian brain can be perturbed by regulatory factors linked to neurodevelopmental or neurodegenerative disorders1-3, suggesting unique regulatory mechanisms. Here we identify functional recursive splice sites (RSS) in long introns of genes expressed in the brain. These RSS are highly conserved in genes with extreme length across diverse vertebrate species and permit step-wise removal of long introns via recursive splicing. Recursive splicing requires initial definition of a “recursive exon” that is located downstream of RSS, and most often contains premature stop codons. Moreover, we show that RSS create a splicing switch driven by splice site competition in order to distinguish primary mRNA isoforms from alternative isoforms that are prevalent in long genes. The recursive exon is not detectable in the dominant mRNA isoform due to recursive splicing, but is completely included when cryptic promoters or other cryptic exons are used. Thus, by coupling inclusion of recursive exons with the use of cryptic elements, RSS act to distinguish new mRNA isoforms emerging from long genes.","abstract":"Recent studies have shown that expression of many genes with exceptionally long introns in the mammalian brain can be perturbed by regulatory factors linked to neurodevelopmental or neurodegenerative disorders1-3, suggesting unique regulatory mechanisms. Here we identify functional recursive splice sites (RSS) in long introns of genes expressed in the brain. These RSS are highly conserved in genes with extreme length across diverse vertebrate species and permit step-wise removal of long introns via recursive splicing. Recursive splicing requires initial definition of a “recursive exon” that is located downstream of RSS, and most often contains premature stop codons. Moreover, we show that RSS create a splicing switch driven by splice site competition in order to distinguish primary mRNA isoforms from alternative isoforms that are prevalent in long genes. The recursive exon is not detectable in the dominant mRNA isoform due to recursive splicing, but is completely included when cryptic promoters or other cryptic exons are used. Thus, by coupling inclusion of recursive exons with the use of cryptic elements, RSS act to distinguish new mRNA isoforms emerging from long genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-02-23T16:24:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001171","title":"Mutational_Analysis_of_Colorectal_PDX_models","description":"Targeted exome  sequencing of patient derived xenografts  from primary colorectal tumours and liver metastases.","abstract":"Targeted exome  sequencing of patient derived xenografts  from primary colorectal tumours and liver metastases.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-02-24T14:00:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001172","title":"Sequencing of heritable Bleeding and Platelet Disorders","description":"The BRIDGE-BPD study aims to discover new causal genes for Bleeding and Platelet Disorders (BPD) by high throughput sequencing using cluster analyses based on improved and standardized deep phenotyping of cases. BPD is one of the 13 Rare Disease projects under the NIHR BioResource Rare Diseases BRIDGE consortium, which is a collaboration aiming to discover the genetic sequence variants underlying unresolved inherited disorders and to improve identification of already identified high penetrance variants.","abstract":"The BRIDGE-BPD study aims to discover new causal genes for Bleeding and Platelet Disorders (BPD) by high throughput sequencing using cluster analyses based on improved and standardized deep phenotyping of cases. BPD is one of the 13 Rare Disease projects under the NIHR BioResource Rare Diseases BRIDGE consortium, which is a collaboration aiming to discover the genetic sequence variants underlying unresolved inherited disorders and to improve identification of already identified high penetrance variants.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-02-24T16:14:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001173","title":"Reference_DNA_standards_for_GCLP_pipeline","description":"The use of reference DNA standards generated from cancer cell lines sequenced in the Cancer Genome Project to establish the sensitivity, specificity, accuracy and reproducibility of the WTSI GCLP sequencing pipeline","abstract":"The use of reference DNA standards generated from cancer cell lines sequenced in the Cancer Genome Project to establish the sensitivity, specificity, accuracy and reproducibility of the WTSI GCLP sequencing pipeline","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-02-26T11:53:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001174","title":"Prediction of pigmentation phenotypes by SNP typing in a Northern German population","description":"Human pigmentation traits are of great interest to many research areas, from ancient DNA analysis to forensic science. We aimed to develop a gene-based predictive model for pigmentation phenotypes in a realistic target population for forensic case work from Northern Germany. Our aim was to determine whether better prediction accuracy can be achieved, or fewer genetic markers may suffice, than in previously studied, genetically more heterogeneous populations. We investigated the association between eye, hair and skin colour, and 12 candidate single nucleotide polymorphisms (SNPs) from six genes. Our study comprised two samples of 300 and 100 individuals from Northern Germany who were carefully characterized with regard to pigmentation phenotypes. The first sample was used to select trait-associated SNPs whereas the second sample served to estimate odds ratios (ORs) and to quantify the predictive capability of the respective SNP genotypes. SNP rs12913832 in HERC2 was found to be strongly associated with blue eye colour (OR=15.6, p&lt;1.2•10-4) and to yield reasonable predictive power (90% sensitivity, 63% specificity). SNP associations with hair and skin colour were weaker and genotypes less predictive. A comparison to two recently published sets of markers to predict eye and hair colour revealed that the consideration of additional SNPs with weak to moderate effect increases the predictive power in Northern Germans for eye colour, but not for hair colour. In addition, fine phenotyping and differentiation of hair colour (light / dark and red tint / no red tint) were found to increase the number of significant genotype-phenotype associations.","abstract":"Human pigmentation traits are of great interest to many research areas, from ancient DNA analysis to forensic science. We aimed to develop a gene-based predictive model for pigmentation phenotypes in a realistic target population for forensic case work from Northern Germany. Our aim was to determine whether better prediction accuracy can be achieved, or fewer genetic markers may suffice, than in previously studied, genetically more heterogeneous populations. We investigated the association between eye, hair and skin colour, and 12 candidate single nucleotide polymorphisms (SNPs) from six genes. Our study comprised two samples of 300 and 100 individuals from Northern Germany who were carefully characterized with regard to pigmentation phenotypes. The first sample was used to select trait-associated SNPs whereas the second sample served to estimate odds ratios (ORs) and to quantify the predictive capability of the respective SNP genotypes. SNP rs12913832 in HERC2 was found to be strongly associated with blue eye colour (OR=15.6, p&lt;1.2•10-4) and to yield reasonable predictive power (90% sensitivity, 63% specificity). SNP associations with hair and skin colour were weaker and genotypes less predictive. A comparison to two recently published sets of markers to predict eye and hair colour revealed that the consideration of additional SNPs with weak to moderate effect increases the predictive power in Northern Germans for eye colour, but not for hair colour. In addition, fine phenotyping and differentiation of hair colour (light / dark and red tint / no red tint) were found to increase the number of significant genotype-phenotype associations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-02-26T12:17:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001175","title":"SECIA_Award","description":"Chromosome capture Hi-C will map interactions between domains (restricted to Mb domains at the moment) at an unprecedented resolution. The technology will be applied to models of cellular aging. For interpreting the architectural dynamics addiyional like methylation status will be obtained. Here we compare the methylation status in corresponding material to the chromosome-capture experiments in cellular aging.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Chromosome capture Hi-C will map interactions between domains (restricted to Mb domains at the moment) at an unprecedented resolution. The technology will be applied to models of cellular aging. For interpreting the architectural dynamics addiyional like methylation status will be obtained. Here we compare the methylation status in corresponding material to the chromosome-capture experiments in cellular aging.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001176","title":"Study of renal cancers and renal cancer metastases","description":null,"abstract":"Study of primary renal cancers as well as metastases derived from renal cancers in various distant organs.","study_type":"Other","pubmed_ids":[27435027,29452772,29973214,30070687,35678045,35800063,36109798],"external_links":null,"is_released":true,"released_date":"2015-02-27T17:06:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001177","title":"Analysis of 456 geographically diverse high coverage sequences of Y chromosome, including 299 newly reported samples suggest recent bottleneck of Y chromosome diversity which coincides with a global change in culture","description":"IMPORTANT: SINCE CURRENTLY ENA IS UNABLE TO MAKE AVAILABLE PARTIAL (here Y chromosomes) GENOMES SEQUENCED BY COMPLETE GENOMICS TECHNOLOGY, PLEASE REFER TO www.ebc.ee/free_data. It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50-100 kya. Here, we present a study of 456 geographically diverse high coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration we date the Y-chromosomal Most Recent Common Ancestor (MRCA) in Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.","abstract":"IMPORTANT: SINCE CURRENTLY ENA IS UNABLE TO MAKE AVAILABLE PARTIAL (here Y chromosomes) GENOMES SEQUENCED BY COMPLETE GENOMICS TECHNOLOGY, PLEASE REFER TO www.ebc.ee/free_data. It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50-100 kya. Here, we present a study of 456 geographically diverse high coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration we date the Y-chromosomal Most Recent Common Ancestor (MRCA) in Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001178","title":"560 whole-genome sequenced breast cancers","description":"A comprehensive characterisation and analysis of 560 human breast cancers through genome-wide approaches including genomics, transcriptomics and epigenomics.","abstract":"A comprehensive characterisation and analysis of 560 human breast cancers through genome-wide approaches including genomics, transcriptomics and epigenomics.","study_type":"Other","pubmed_ids":[27135926,28112740],"external_links":null,"is_released":true,"released_date":"2015-03-02T14:24:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001179","title":"Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment.","description":"Temozolomide (TMZ) increases the overall survival of patients with glioblastoma (GBM), but its role in the clinical management of diffuse low-grade gliomas (LGG) is still being defined. DNA hypermethylation of the O 6 -methylguanine-DNA methyltransferase (MGMT) promoter is associated with an improved response to TMZ treatment, while inactivation of the DNA mismatch repair (MMR) pathway is associated with therapeutic resistance and TMZ-induced mutagenesis. We previously demonstrated that TMZ treatment of LGG induces driver mutations in the RB and AKT-mTOR pathways, which may drive malignant progression to secondary GBM. To better understand the mechanisms underlying TMZ-induced mutagenesis and malignant progression, we explored the evolution of MGMT methylation and genetic alterations affecting MMR genes in a cohort of 34 treatment-naïve LGGs and their recurrences. Recurrences with TMZ-associated hypermutation had increased MGMT methylation compared to their untreated initial tumors and higher overall MGMT methylation compared to TMZ-treated non-hypermutated recurrences. A TMZ-associated mutation in one or more MMR genes was observed in five out of six TMZ-treated hypermutated recurrences. In two cases, pre-existing heterozygous deletions encompassing MGMT, or an MMR gene, were followed by TMZ-associated mutations in one of the genes of interest. These results suggest that tumor cells with methylated MGMT may undergo positive selection during TMZ treatment in the context of MMR deficiency.","abstract":"Temozolomide (TMZ) increases the overall survival of patients with glioblastoma (GBM), but its role in the clinical management of diffuse low-grade gliomas (LGG) is still being defined. DNA hypermethylation of the O 6 -methylguanine-DNA methyltransferase (MGMT) promoter is associated with an improved response to TMZ treatment, while inactivation of the DNA mismatch repair (MMR) pathway is associated with therapeutic resistance and TMZ-induced mutagenesis. We previously demonstrated that TMZ treatment of LGG induces driver mutations in the RB and AKT-mTOR pathways, which may drive malignant progression to secondary GBM. To better understand the mechanisms underlying TMZ-induced mutagenesis and malignant progression, we explored the evolution of MGMT methylation and genetic alterations affecting MMR genes in a cohort of 34 treatment-naïve LGGs and their recurrences. Recurrences with TMZ-associated hypermutation had increased MGMT methylation compared to their untreated initial tumors and higher overall MGMT methylation compared to TMZ-treated non-hypermutated recurrences. A TMZ-associated mutation in one or more MMR genes was observed in five out of six TMZ-treated hypermutated recurrences. In two cases, pre-existing heterozygous deletions encompassing MGMT, or an MMR gene, were followed by TMZ-associated mutations in one of the genes of interest. These results suggest that tumor cells with methylated MGMT may undergo positive selection during TMZ treatment in the context of MMR deficiency.","study_type":"Other","pubmed_ids":[25724300],"external_links":null,"is_released":true,"released_date":"2015-03-03T21:54:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001180","title":"Methylation_changes_in_OA_patients_with_chronic_exposure_to_cobalt_and_chromium","description":"We have whole blood from a population of 70 patients, half exposed chronically to an excessof metals cobalt and chromium. The 2 groups are age, sex, and OA diagnosis matched. The2 groups have systemic differences in bone mass and turnover, and other systemicdifferences.We will type the cohort of 70 individuals on the Illumina 450k methylation array and willcompare between the two groups.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We have whole blood from a population of 70 patients, half exposed chronically to an excessof metals cobalt and chromium. The 2 groups are age, sex, and OA diagnosis matched. The2 groups have systemic differences in bone mass and turnover, and other systemicdifferences.We will type the cohort of 70 individuals on the Illumina 450k methylation array and willcompare between the two groups.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-05T14:07:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001181","title":"de_novo_mutations_in_cell_free_foetal_DNA__cffDNA_","description":"The aim of this project is to develop and test a method for detecting and validating de novo mutations from cell-free foetal DNA by targeted sequencing. We have designed an Agilent SureSelect bait library with probes around sites that we believe to be likely to contain de novo mutations, based on a previous round of whole genome sequencing of the same samples. The bait library also includes the exons of genes that have been shown to be involved in developmental disorders (the DDG2P genes). There are four samples, consisting of the mother, the father, and the child (obtained by chorionic villus sampling or CVS), as well as plasma DNA obtained from the mother (a combination of maternal and cell-free foetal DNA, or cffDNA). After the pull-down, the four samples will be sequenced on two HiSeq lanes.","abstract":"The aim of this project is to develop and validate a method to detect de novo mutations in a foetal genome through deep sequencing of cell-free DNA from the plasma of a pregnant women. Approximately 10-15% of this cell-free DNA is from the foetus. By  sequencing the maternal plasma very deeply and adapting our current de novo mutation calling algorithms we hope to demonstrate that de novo mutations can be reliably detected in this manner.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001182","title":"Genome_Diversity_in_Africa_Project___ancient_samples___standard_libraries","description":"Given the central importance of Africa to studies of human origins, genetic diversity and disease susceptibility, large-scale and representative characterisation of genetic diversity in Africa is needed. Analyses of ancient DNA from Africa would complement sequencing of modern African populations and provide unique opportunities to transform our understanding of the pre-history of the region. This approach would greatly refine our understanding of population structure and gene flow in Africa and globally, including genetic signatures of ancient admixture. This low coverage sequencing experiment will allow us to test and refine our pipeline for ancient DNA sequencing.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Given the central importance of Africa to studies of human origins, genetic diversity and disease susceptibility, large-scale and representative characterisation of genetic diversity in Africa is needed. Analyses of ancient DNA from Africa would complement sequencing of modern African populations and provide unique opportunities to transform our understanding of the pre-history of the region. This approach would greatly refine our understanding of population structure and gene flow in Africa and globally, including genetic signatures of ancient admixture. This low coverage sequencing experiment will allow us to test and refine our pipeline for ancient DNA sequencing.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-08T07:23:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001183","title":"Neuroblastoma relapse trio series from the AMC","description":"The majority of neuroblastoma patients have tumors that initially respond to chemotherapy, but a large proportion of patients will experience therapy-resistant relapses. The molecular basis of this aggressive phenotype is unknown. Whole genome sequencing of 23 paired diagnostic and relapsed neuroblastomas showed clonal evolution from the diagnostic tumor with a median of 29 somatic mutations unique to the relapse sample. Eighteen of the 23 relapse tumors (78%) showed RAS-MAPK pathway mutations. Seven events were detected only in the relapse tumor while the others showed clonal enrichment. In neuroblastoma cell lines we also detected a high frequency of activating mutations in the RAS-MAPK pathway (11/18, 61%) and these lesions predicted for sensitivity to MEK inhibition in vitro and in vivo. Our findings provide a rationale for genetic characterization of relapse neuroblastoma and show that RAS-MAPK pathway mutations may function as a biomarker for new therapeutic approaches to refractory disease.","abstract":"The majority of neuroblastoma patients have tumors that initially respond to chemotherapy, but a large proportion of patients will experience therapy-resistant relapses. The molecular basis of this aggressive phenotype is unknown. Whole genome sequencing of 23 paired diagnostic and relapsed neuroblastomas showed clonal evolution from the diagnostic tumor with a median of 29 somatic mutations unique to the relapse sample. Eighteen of the 23 relapse tumors (78%) showed RAS-MAPK pathway mutations. Seven events were detected only in the relapse tumor while the others showed clonal enrichment. In neuroblastoma cell lines we also detected a high frequency of activating mutations in the RAS-MAPK pathway (11/18, 61%) and these lesions predicted for sensitivity to MEK inhibition in vitro and in vivo. Our findings provide a rationale for genetic characterization of relapse neuroblastoma and show that RAS-MAPK pathway mutations may function as a biomarker for new therapeutic approaches to refractory disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-08T20:49:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001184","title":"Institut Curie Neuroblastoma Whole Genome Sequencing Diagnosis Relapse","description":"Neuroblastoma, a clinically heterogeneous pediatric cancer, is characterized by distinct genomic profiles but few recurrent mutations. As neuroblastoma is expected to have high degree of genetic heterogeneity, study of neuroblastoma's clonal evolution with deep coverage whole-genome sequencing of diagnosis and relapse samples will lead to a better understanding of the molecular events associated with relapse.  Samples were included in this study if sufficient DNA from constitutional, diagnosis and relapse tumors was available for WGS.  Whole genome sequencing was performed on trios (constitutional, diagnose and relapse DNA) from eight patients using Illumina Hi-seq2500 leading to paired-ends (PE) 90x90 for 6 of them and 100x100 for two. Expected coverage for sample NB0175 100x100bp was 30X for tumor and constitutional samples. For the seven other patients expected coverage was 80X for tumor samples with PE 100x100, 100X in the other tumor samples and 50X for all constitutional samples (see table 1). Following alignment with BWA (Li et al., Oxford J, 2009 Jul) allowing up to 4% of mismatches, bam files were cleaned up according to the Genome Analysis Toolkit (GATK) recommendations (Van der Auwera et al., Current Protocols in Bioinformatics, 2013, picard-1.45, GenomeAnalysisTK-2.2-16).   Variant calling was performed in parallel using 3 variant callers: GenomeAnalysisTK-2.2-16, Samtools-0.1.18 and MuTect-1.1.4 (McKenna et al., Genome Res, 2010; Li et al., Oxford J, 2009 Aug; Cibulskis et al., Nature, 2013). Annovar-v2012-10-23 with cosmic-v64 and dbsnp-v137 were used for the annotation and RefSeq for the structural annotation. For GATK and Samtools,  single nucleotide variants (SNVs) with a quality under 30, a depth of coverage under 6 or with less than 2 reads supporting the variant were filter out. MuTect with parameters following GATK and Samtools thresholds have been used to filter our irrelevant variants. .SNVs within and around exons of coding genes overlapping splice sites.. Then,variants reported in more than 1% of the population in the 1000 genomes (1000gAprl_2012) or Exome Sequencing Project (ESP6500) have been discarded in order to filter polymorphisms. Finally, synonymous variants were filtered out. MuTect focuses on somatic by filtering with constitutional sample. Mpileup comparison between constitutional and somatic DNAs  allowed us to focus also on tumor specific SNVs with GATK and Samtools. Finally, every SNV called by our pipeline and also supported in any constitutional samples were filtered our in order to prevent putative constitutional DNA coverage deficiency.   Then we analyzed CNVs (copy number variants) with HMMcopy-v0.1.1 (Gavin et al., Genome Res, 2012) and control-FREEC-v6.7 (Boeva et al., Bioinformatics 2011) with a respective window of 2000bp and 1000 bp, and auto-correction of normal contamination of tumor samples for Control-FREEC.  Finally we explored Structural variants (SVs) including deletions, inversions, tandem duplications and translocations using DELLY-v0.5.5 with standard parameters (Rausch et al., Oxford J, 2012). In tumors, at least 10 supporting reads were required to make a call and 5 supporting reads for the sample NB0175 with a coverage of only 40X (see table 2). To predict SVs in constitutional samples for subsequent somatic filtering, only 2 supporting reads were required in order not to miss one. To identify somatic events, all the SVs in each normal sample were first flanked by 500 bp in both directions and any SVs called in a tumor sample which was in the combined flanked regions of respective normal sample was removed (see graph 1). Deletions with more than 5 genes impacted or larger than 1Mb and inversions or tandem duplications covering more than 4 genes, were removed. We focused on exonic and splicing events for deletions, inversions, and tandem duplications. For translocation, we keep all SVs that occurred in intronic, exonic, 5'UTR, upstream or splicing regions.  Bioinformatics detection of variations with Deep sequencing approach Once PE reads merged and adaptors trimmed by SeqPrep with default parameters, merged reads were aligned via the BWA (Li H. and Durbin R. 2009 PMID 19451168) allowing up to 1 differences in the 22-base-long seeds and reporting only unique alignments. Only reads having a mapping quality 20 or more have been further analysed. Variant calling software was not used, since we aimed to predict variations at low frequencies, observed in less than 1% of reads. Such variants require a custom approach. Using DepthOfCoverage functions of the Genome Analysis Toolkit (GATK) v2.13.2 (McKenna A, et al., 2010 Genome Research PMID: 20644199), we focused on high quality coverage of bases A, C, G and T at the targeted variant position. Depth of coverage of each base following a mapping quality higher than 20 and a base quality higher than 10 have been taken into account in order to focus only on high quality data. Aiming to determine the background level of variability at the studied regions, 10 control samples were included in the analysis. The same approach and filtering criteria have been applied as introduced above over the entire amplicons.  In order to highlight variants, for each sample the frequencies of each bases at each amplicon position were then compared to those observed in the set of controls. Statistical analyses were performed with the R statistical software (http://www.R-project.org). Fisher’s exact two-sided tests with a Bonferroni correction were performed to compare percentages of bases between the data sets, i.e. for a given base between a case and the controls. Finally, significant variations were filtered-in once (i) a significant increase in the percentage of avariant base and (ii) a significant decrease in the percentage of it's reference base following our p.values criteria was observed (p.val &lt; 0.05).","abstract":"Neuroblastoma, a clinically heterogeneous pediatric cancer, is characterized by distinct genomic profiles but few recurrent mutations. As neuroblastoma is expected to have high degree of genetic heterogeneity, study of neuroblastoma's clonal evolution with deep coverage whole-genome sequencing of diagnosis and relapse samples will lead to a better understanding of the molecular events associated with relapse.  Samples were included in this study if sufficient DNA from constitutional, diagnosis and relapse tumors was available for WGS.  Whole genome sequencing was performed on trios (constitutional, diagnose and relapse DNA) from eight patients using Illumina Hi-seq2500 leading to paired-ends (PE) 90x90 for 6 of them and 100x100 for two. Expected coverage for sample NB0175 100x100bp was 30X for tumor and constitutional samples. For the seven other patients expected coverage was 80X for tumor samples with PE 100x100, 100X in the other tumor samples and 50X for all constitutional samples (see table 1). Following alignment with BWA (Li et al., Oxford J, 2009 Jul) allowing up to 4% of mismatches, bam files were cleaned up according to the Genome Analysis Toolkit (GATK) recommendations (Van der Auwera et al., Current Protocols in Bioinformatics, 2013, picard-1.45, GenomeAnalysisTK-2.2-16).   Variant calling was performed in parallel using 3 variant callers: GenomeAnalysisTK-2.2-16, Samtools-0.1.18 and MuTect-1.1.4 (McKenna et al., Genome Res, 2010; Li et al., Oxford J, 2009 Aug; Cibulskis et al., Nature, 2013). Annovar-v2012-10-23 with cosmic-v64 and dbsnp-v137 were used for the annotation and RefSeq for the structural annotation. For GATK and Samtools,  single nucleotide variants (SNVs) with a quality under 30, a depth of coverage under 6 or with less than 2 reads supporting the variant were filter out. MuTect with parameters following GATK and Samtools thresholds have been used to filter our irrelevant variants. .SNVs within and around exons of coding genes overlapping splice sites.. Then,variants reported in more than 1% of the population in the 1000 genomes (1000gAprl_2012) or Exome Sequencing Project (ESP6500) have been discarded in order to filter polymorphisms. Finally, synonymous variants were filtered out. MuTect focuses on somatic by filtering with constitutional sample. Mpileup comparison between constitutional and somatic DNAs  allowed us to focus also on tumor specific SNVs with GATK and Samtools. Finally, every SNV called by our pipeline and also supported in any constitutional samples were filtered our in order to prevent putative constitutional DNA coverage deficiency.   Then we analyzed CNVs (copy number variants) with HMMcopy-v0.1.1 (Gavin et al., Genome Res, 2012) and control-FREEC-v6.7 (Boeva et al., Bioinformatics 2011) with a respective window of 2000bp and 1000 bp, and auto-correction of normal contamination of tumor samples for Control-FREEC.  Finally we explored Structural variants (SVs) including deletions, inversions, tandem duplications and translocations using DELLY-v0.5.5 with standard parameters (Rausch et al., Oxford J, 2012). In tumors, at least 10 supporting reads were required to make a call and 5 supporting reads for the sample NB0175 with a coverage of only 40X (see table 2). To predict SVs in constitutional samples for subsequent somatic filtering, only 2 supporting reads were required in order not to miss one. To identify somatic events, all the SVs in each normal sample were first flanked by 500 bp in both directions and any SVs called in a tumor sample which was in the combined flanked regions of respective normal sample was removed (see graph 1). Deletions with more than 5 genes impacted or larger than 1Mb and inversions or tandem duplications covering more than 4 genes, were removed. We focused on exonic and splicing events for deletions, inversions, and tandem duplications. For translocation, we keep all SVs that occurred in intronic, exonic, 5'UTR, upstream or splicing regions.  Bioinformatics detection of variations with Deep sequencing approach Once PE reads merged and adaptors trimmed by SeqPrep with default parameters, merged reads were aligned via the BWA (Li H. and Durbin R. 2009 PMID 19451168) allowing up to 1 differences in the 22-base-long seeds and reporting only unique alignments. Only reads having a mapping quality 20 or more have been further analysed. Variant calling software was not used, since we aimed to predict variations at low frequencies, observed in less than 1% of reads. Such variants require a custom approach. Using DepthOfCoverage functions of the Genome Analysis Toolkit (GATK) v2.13.2 (McKenna A, et al., 2010 Genome Research PMID: 20644199), we focused on high quality coverage of bases A, C, G and T at the targeted variant position. Depth of coverage of each base following a mapping quality higher than 20 and a base quality higher than 10 have been taken into account in order to focus only on high quality data. Aiming to determine the background level of variability at the studied regions, 10 control samples were included in the analysis. The same approach and filtering criteria have been applied as introduced above over the entire amplicons.  In order to highlight variants, for each sample the frequencies of each bases at each amplicon position were then compared to those observed in the set of controls. Statistical analyses were performed with the R statistical software (http://www.R-project.org). Fisher’s exact two-sided tests with a Bonferroni correction were performed to compare percentages of bases between the data sets, i.e. for a given base between a case and the controls. Finally, significant variations were filtered-in once (i) a significant increase in the percentage of avariant base and (ii) a significant decrease in the percentage of it's reference base following our p.values criteria was observed (p.val &lt; 0.05).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-09T12:11:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001185","title":"Inherited metabolic disease","description":"Exome sequencing of a family with inherited metabolic disease, includding the index case (affected patient) as well as healthy parents.","abstract":"Exome sequencing of a family with inherited metabolic disease, includding the index case (affected patient) as well as healthy parents.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001186","title":"EXOME SEQUENCING OF INHERITED METABOLIC DISEASE","description":"Exome sequencing of a family with inherited metabolic disease, includding the index case (affected patient) as well as healthy parents.","abstract":"Exome sequencing of a family with inherited metabolic disease, includding the index case (affected patient) as well as healthy parents.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001187","title":"EXOME SEQUENCING OF INHERITED METABOLIC DISEASE","description":"Exome sequencing of a family with inherited metabolic disease, includding the index case (affected patient) as well as healthy parents.","abstract":"Exome sequencing of a family with inherited metabolic disease, includding the index case (affected patient) as well as healthy parents.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001188","title":"INHERITED METABOLIC DISEASE","description":"Exome sequencing of a family with inherited metabolic disease, includding the index case (affected patient) as well as healthy parents.","abstract":"Exome sequencing of a family with inherited metabolic disease, includding the index case (affected patient) as well as healthy parents.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001189","title":"EXOME SEQUENCING OF INHERITED METABOLIC DISEASE","description":"Exome sequencing of 6 families with inherited metabolic diseases. In families 1 to 4 the study include the index cases (affected patients) as well as their healthy parents. In family 5 only two affected siblings are included. In family 6 just one affected individual is included. Families 5 and 6 had evidence  of consanguinity.All patients are affected of inborn errors of metabolism with an autosomic recessive inheritance pattern. In particular all these patients had mitochondrial energy metabolism deficiencies.","abstract":"Exome sequencing of 6 families with inherited metabolic diseases. In families 1 to 4 the study include the index cases (affected patients) as well as their healthy parents. In family 5 only two affected siblings are included. In family 6 just one affected individual is included. Families 5 and 6 had evidence  of consanguinity.All patients are affected of inborn errors of metabolism with an autosomic recessive inheritance pattern. In particular all these patients had mitochondrial energy metabolism deficiencies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001190","title":"Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma","description":"Follicular lymphoma (FL) is an incurable B-cell malignancy characterized by the t(14;18) and mutations in one or more components of the epigenome.  Whilst frequent gene mutations in signaling pathways, including JAK-STAT, NOTCH and NF-κB, have also been defined, the spectrum of these mutations typically overlap with the closely-related diffuse large B cell lymphoma (DLBCL). A combination of discovery exome and extended targeted sequencing revealed recurrent somatic mutations in RRAGC uniquely enriched in FL patients (17%). More than half of the mutations preferentially co-occurred with ATP6V1B2 and ATP6AP1 mutations, components of the vacuolar H+-adenosine triphosphate ATPase (v-ATPase) known to be necessary for amino acid-dependent mTORC1 activation. RagC mutants increased raptor binding whilst rendering mTORC1 signaling resistant to amino acid deprivation through nucleotide-independent mechanisms. Collectively, the activating nature of the RRAGC mutations, their existence within the dominant clone and stability during disease progression supports their potential as an excellent candidate to be therapeutically exploited.","abstract":"Follicular lymphoma (FL) is an incurable B-cell malignancy characterized by the t(14;18) and mutations in one or more components of the epigenome.  Whilst frequent gene mutations in signaling pathways, including JAK-STAT, NOTCH and NF-κB, have also been defined, the spectrum of these mutations typically overlap with the closely-related diffuse large B cell lymphoma (DLBCL). A combination of discovery exome and extended targeted sequencing revealed recurrent somatic mutations in RRAGC uniquely enriched in FL patients (17%). More than half of the mutations preferentially co-occurred with ATP6V1B2 and ATP6AP1 mutations, components of the vacuolar H+-adenosine triphosphate ATPase (v-ATPase) known to be necessary for amino acid-dependent mTORC1 activation. RagC mutants increased raptor binding whilst rendering mTORC1 signaling resistant to amino acid deprivation through nucleotide-independent mechanisms. Collectively, the activating nature of the RRAGC mutations, their existence within the dominant clone and stability during disease progression supports their potential as an excellent candidate to be therapeutically exploited.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-10T13:33:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001191","title":"Genome-wide DNA-methylation assessment by MethylCap-seq and Infinium HumanMethylation450 BeadChips: an independent large-scale comparison","description":"DNA-methylation is an important epigenetic feature in health and disease. Two cost-efficient genome-scale methodologies to assess DNA-methylation are MethylCap-seq and Illumina's Infinium HumanMethylation450 BeadChips (HM450). However, objective information regarding the best-suited methodology for a specific research question is scant. Therefore, we performed a large-scale evaluation on a set of 70 brain tissue samples obtained from 65 glioblastoma and 5 non-tumoral brain tissues, using a gold standard free Bayesian modeling procedure. While conditional specificity was adequate for both approaches, conditional sensitivity was systematically higher for HM450. Also the genome-wide characteristics were compared, revealing that the HM450 probes assess less than 10% of the regions identified as methylated by MethylCap-seq. Hence the latter method may detect more potentially relevant DNA-methylation, defined by either functional location or previously reported differentially methylated candidate regions. Our results therefore indicate that – at least for the tissue under study - both methodologies are complementary, with a higher sensitivity for HM450, but a far larger genome-wide coverage for MethylCap-seq. Note that here only the relevant MethylCap-seq data is deposited, for the HM450 data we refer to GEO (GSE60274).","abstract":"DNA-methylation is an important epigenetic feature in health and disease. Two cost-efficient genome-scale methodologies to assess DNA-methylation are MethylCap-seq and Illumina's Infinium HumanMethylation450 BeadChips (HM450). However, objective information regarding the best-suited methodology for a specific research question is scant. Therefore, we performed a large-scale evaluation on a set of 70 brain tissue samples obtained from 65 glioblastoma and 5 non-tumoral brain tissues, using a gold standard free Bayesian modeling procedure. While conditional specificity was adequate for both approaches, conditional sensitivity was systematically higher for HM450. Also the genome-wide characteristics were compared, revealing that the HM450 probes assess less than 10% of the regions identified as methylated by MethylCap-seq. Hence the latter method may detect more potentially relevant DNA-methylation, defined by either functional location or previously reported differentially methylated candidate regions. Our results therefore indicate that – at least for the tissue under study - both methodologies are complementary, with a higher sensitivity for HM450, but a far larger genome-wide coverage for MethylCap-seq. Note that here only the relevant MethylCap-seq data is deposited, for the HM450 data we refer to GEO (GSE60274).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-10T13:47:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001192","title":"1417 pairs of BLCA-CN","description":"We sequenced 103 pairs of BLCA-CN","abstract":"We sequenced 103 pairs of BLCA-CN","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001193","title":"PKDL_RNA_Seq","description":"A pilot project to evaluate the potential for defining whole lesion transcriptomes from paraffin embedded tissue sections, obtained from skin biopsies. The aim is to utilise this procedure to examine pre and post chemotherapy in patients with post kala azar dermal leishmaniasis. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"A pilot project to evaluate the potential for defining whole lesion transcriptomes from paraffin embedded tissue sections, obtained from skin biopsies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001194","title":"Exome sequencing","description":"Exome sequence Pfizer &amp; TwinsUK","abstract":"Exome sequence Pfizer &amp; TwinsUK","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-12T10:18:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001195","title":"ICGC Breast Cancer Project","description":"A comprehensive characterisation and analysis of human breast cancers through genome-wide approaches including genomics, transcriptomics and epigenomics.","abstract":"A comprehensive characterisation and analysis of human breast cancers through genome-wide approaches including genomics, transcriptomics and epigenomics.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-12T10:20:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001196","title":"BLUEPRINT DNA methylation profiling of B-cell differentiation using Illumina HumanMethylation 450K BeadArray","description":"We performed DNA methylation analysis in 6 different mature B-cell subpopulations using the Illumina HumanMethylation 450K BeadArray. In particular, we analyzed naive B cells from peripheral blood (naiBC); naive B cells from tonsil (t-naiBC); germinal center B cells (gcBC); plasma cells from tonsil (t-PC); memory B cells from peripheral blood (memBC) and plasma cells from bone marrow (bm-PC). All the samples were isolated from healthy donors and we analyzed 3 to 9 biological replicates of each subtype.","abstract":"We performed DNA methylation analysis in 6 different mature B-cell subpopulations using the Illumina HumanMethylation 450K BeadArray. In particular, we analyzed naive B cells from peripheral blood (naiBC); naive B cells from tonsil (t-naiBC); germinal center B cells (gcBC); plasma cells from tonsil (t-PC); memory B cells from peripheral blood (memBC) and plasma cells from bone marrow (bm-PC). All the samples were isolated from healthy donors and we analyzed 3 to 9 biological replicates of each subtype.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-13T16:40:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001197","title":"BLUEPRINT Gene expression analysis during human B-cell differentiation using the Affymetrix Human Genome U219 Array","description":"We performed gene expression analysis using the Affymetrix Human Genome U219 Array of 9 subpopulations covering the complete B-cell maturation program: hematopoietic progenitor cells (HPC);  pre-B-I cells (preB1C);  pre-B-II cells (preB2C); naive B cells from peripheral blood (naiBC); naive B cells from tonsil (t-naiBC); germinal center B cells (gcBC); plasma cells from tonsil (t-PC); memory B cells from peripheral blood (memBC) and plasma cells from bone marrow (bm-PC). All the samples were isolated from healthy donors and, with the exception of bm-PC (only 1 replicate), we used 3 to 11 biological replicates of each subtype.","abstract":"We performed gene expression analysis using the Affymetrix Human Genome U219 Array of 9 subpopulations covering the complete B-cell maturation program: hematopoietic progenitor cells (HPC);  pre-B-I cells (preB1C);  pre-B-II cells (preB2C); naive B cells from peripheral blood (naiBC); naive B cells from tonsil (t-naiBC); germinal center B cells (gcBC); plasma cells from tonsil (t-PC); memory B cells from peripheral blood (memBC) and plasma cells from bone marrow (bm-PC). All the samples were isolated from healthy donors and, with the exception of bm-PC (only 1 replicate), we used 3 to 11 biological replicates of each subtype.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-13T16:49:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001198","title":"Exome sequencing in Moebius syndrome","description":"Möbius syndrome (MBS; MIM 157900) is a neurological disorder that is characterized by paralysis of the facial nerves and variable other congenital anomalies. The etiology of this syndrome has been an enigma since the initial description in 1880 by von Graaefe and in 1888 by Möbius, and it has been debated for decades whether MBS has a genetic or a non-genetic etiology. Here, we reveal various de novo mutations affecting two genes, PLXND1 and REV3L. The finding that de novo mutations can cause MBS will have considerable impact on further research, as well as in diagnostics. PLXND1 and REV3L represent totally unrelated pathways involved in hindbrain development: neural migration and DNA translesion synthesis, essential for the replication of endogenously damaged DNA. Interestingly, analysis of Plxnd1 and Rev3l-mutant mice revealed that both genetic defects converge at the facial branchiomotor nucleus, affecting either motoneuron migration or proliferation.","abstract":"Möbius syndrome (MBS; MIM 157900) is a neurological disorder that is characterized by paralysis of the facial nerves and variable other congenital anomalies. The etiology of this syndrome has been an enigma since the initial description in 1880 by von Graaefe and in 1888 by Möbius, and it has been debated for decades whether MBS has a genetic or a non-genetic etiology. Here, we reveal various de novo mutations affecting two genes, PLXND1 and REV3L. The finding that de novo mutations can cause MBS will have considerable impact on further research, as well as in diagnostics. PLXND1 and REV3L represent totally unrelated pathways involved in hindbrain development: neural migration and DNA translesion synthesis, essential for the replication of endogenously damaged DNA. Interestingly, analysis of Plxnd1 and Rev3l-mutant mice revealed that both genetic defects converge at the facial branchiomotor nucleus, affecting either motoneuron migration or proliferation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001199","title":"MINCR is a MYC-induced lncRNA able to modulate MYC’s transcriptional network in Burkitt lymphoma cells","description":"Despite the established role of the transcription factor MYC in cancer, little is known about the involvement of lncRNAs in mediating MYC’s function. Here we have intersected RNA-sequencing data from MYC-inducible cell lines, from a cohort of 91 mature B-cell lymphomas and from sorted germinal-center B-cells. By this approach, we identified 13 lncRNAs differentially expressed in IG-MYC-positive Burkitt lymphoma and regulated by MYC in the model cell lines. Among them we focused on a lncRNA that we named MINCR, showing a strong correlation with MYC expression in MYC-positive lymphomas and in pancreatic ductal adenocarcinomas. RNAi experiments showed that MINCR controls cellular viability by influencing the expression of MYC-regulated cell cycle genes. Finally we provide evidences that down-regulation of AURKA, AURKB and CTD1 may explain the reduction in cellular proliferation observed upon MINCR knock-down. We therefore suggest that MINCR acts as a modulator of MYC transcriptional control of cell cycle genes.","abstract":"Despite the established role of the transcription factor MYC in cancer, little is known about the involvement of lncRNAs in mediating MYC’s function. Here we have intersected RNA-sequencing data from MYC-inducible cell lines, from a cohort of 91 mature B-cell lymphomas and from sorted germinal-center B-cells. By this approach, we identified 13 lncRNAs differentially expressed in IG-MYC-positive Burkitt lymphoma and regulated by MYC in the model cell lines. Among them we focused on a lncRNA that we named MINCR, showing a strong correlation with MYC expression in MYC-positive lymphomas and in pancreatic ductal adenocarcinomas. RNAi experiments showed that MINCR controls cellular viability by influencing the expression of MYC-regulated cell cycle genes. Finally we provide evidences that down-regulation of AURKA, AURKB and CTD1 may explain the reduction in cellular proliferation observed upon MINCR knock-down. We therefore suggest that MINCR acts as a modulator of MYC transcriptional control of cell cycle genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-20T12:32:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001200","title":"Identification of Somatic Alterations in colorectal cancer patients by Next-generation Sequencing","description":"5 WGS sequencing and 35 WES of Chinese colorectal cancer cases","abstract":"5 WGS sequencing and 35 WES of Chinese colorectal cancer cases","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001201","title":"Identification of de novo mutations associated with Möbius syndrome.","description":"Möbius syndrome (MBS) is a neurological disorder that is characterized by paralysis of the facial nerves and variable other congenital anomalies. The etiology of this syndrome has been enigmatic since the initial descriptions by von Graefe in 1880 and by Möbius in 1888, and it has been debated for decades whether MBS has a genetic or a non-genetic etiology. Here, we report a number of de novo mutations affecting two genes, PLXND1 and REV3L. PLXND1 and REV3L represent totally unrelated pathways involved in hindbrain development: neural migration and DNA translesion synthesis, essential for the replication of endogenously damaged DNA, respectively. Interestingly, analysis of Plxnd1 and Rev3l-mutant mice shows that disruption of these separate pathways converge at the facial branchiomotor nucleus, affecting either motoneuron migration or proliferation. The finding that PLXND1 and REV3L mutations are responsible for a proportion of MBS patients suggests that de novo mutations in other genes might account for other MBS patients.","abstract":"Möbius syndrome (MBS) is a neurological disorder that is characterized by paralysis of the facial nerves and variable other congenital anomalies. The etiology of this syndrome has been enigmatic since the initial descriptions by von Graefe in 1880 and by Möbius in 1888, and it has been debated for decades whether MBS has a genetic or a non-genetic etiology. Here, we report a number of de novo mutations affecting two genes, PLXND1 and REV3L. PLXND1 and REV3L represent totally unrelated pathways involved in hindbrain development: neural migration and DNA translesion synthesis, essential for the replication of endogenously damaged DNA, respectively. Interestingly, analysis of Plxnd1 and Rev3l-mutant mice shows that disruption of these separate pathways converge at the facial branchiomotor nucleus, affecting either motoneuron migration or proliferation. The finding that PLXND1 and REV3L mutations are responsible for a proportion of MBS patients suggests that de novo mutations in other genes might account for other MBS patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001202","title":"CONSERTING: integrating copy number analysis with structural variation detection","description":"We developed Copy Number Segmentation by Regression Tree in Next Generation Sequencing (CONSERTING), a novel algorithm for detecting somatic copy number alteration (CNA) using whole-genome sequencing (WGS) data.  CONSERTING performs iterative analysis of segmentation by read depth change and localized structural variation detection to achieve high accuracy and sensitivity. Analysis of 43 pediatric and adult cancer genomes revealed novel oncogenic CNAs, complex re-arrangements and subclonal CNAs missed by alternative approaches. This study contains all data for \"CONSERTING: an accurate method for detecting somatic DNA copy number alterations in whole genome sequencing data\", which was previously split between EGAS00001001202 and EGAS00001001050.","abstract":"We developed Copy Number Segmentation by Regression Tree in Next Generation Sequencing (CONSERTING), a novel algorithm for detecting somatic copy number alteration (CNA) using whole-genome sequencing (WGS) data.  CONSERTING performs iterative analysis of segmentation by read depth change and localized structural variation detection to achieve high accuracy and sensitivity. Analysis of 43 pediatric and adult cancer genomes revealed novel oncogenic CNAs, complex re-arrangements and subclonal CNAs missed by alternative approaches. This study contains all data for \"CONSERTING: an accurate method for detecting somatic DNA copy number alterations in whole genome sequencing data\", which was previously split between EGAS00001001202 and EGAS00001001050.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-24T20:23:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001203","title":"Pilot_experiment_on_functional_genomics_in_osteoarthritis_RNA","description":"The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of large joint (hip and knee) osteoarthritis which culminates in the need for total joint replacement (TJR). In this pilot we will assess the feasibility of the approach in the relevant tissue. We will obtain diseased and non-diseased tissue (cartilage and endochondral bone) following TJR, coupled with a blood sample, from 12 patients. We will characterise the 12 pairs of diseased and non-diseased tissue samples in terms of transcription (RNASeq) The pilot will help assess the feasibility of isolating sufficient levels of starting material for the different approaches, and will instigate the development of analytical approaches to synthesising the resulting data.","abstract":"The aim of this work was to apply an integrated systems approach to understand the biological underpinnings of knee osteoarthritis which culminates in the need for total joint replacement (TJR). We obtained diseased and non-diseased cartilage following TJR, coupled with a blood sample, from 12 patients. We characterised the 12 pairs of diseased and non-diseased tissue samples in terms of transcription (RNASeq).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-25T12:45:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001204","title":"G&T-seq: parallel sequencing of the genomes and transcriptomes of single cells","description":"The ability to simultaneously sequence the genome and transcriptome of the same single cell offersa powerful means to dissect functional genetic heterogeneity at the cellular level. Here we describeG&amp;T-seq, a method for separating and sequencing genomic DNA and full-length mRNA from singlecells. By applying G&amp;T-seq to over 220 single cells we reveal cellular properties that cannot beinferred from DNA or RNA sequencing alone, including associations between DNA copy numbervariation and gene expression dosage. We further demonstrate the detection of coding interchromosomalfusions and single nucleotide variants in both the genomes and transcriptomes ofindividual cells. G&amp;T-seq enables the study of genotype-phenotype associations in single cells, andthe investigation of DNA cell lineage trees of healthy and diseased tissues with transcriptome inferredcell types and states.","abstract":"The ability to simultaneously sequence the genome and transcriptome of the same single cell offersa powerful means to dissect functional genetic heterogeneity at the cellular level. Here we describeG&amp;T-seq, a method for separating and sequencing genomic DNA and full-length mRNA from singlecells. By applying G&amp;T-seq to over 220 single cells we reveal cellular properties that cannot beinferred from DNA or RNA sequencing alone, including associations between DNA copy numbervariation and gene expression dosage. We further demonstrate the detection of coding interchromosomalfusions and single nucleotide variants in both the genomes and transcriptomes ofindividual cells. G&amp;T-seq enables the study of genotype-phenotype associations in single cells, andthe investigation of DNA cell lineage trees of healthy and diseased tissues with transcriptome inferredcell types and states.","study_type":"Whole Genome Sequencing","pubmed_ids":[25915121],"external_links":null,"is_released":true,"released_date":"2015-03-26T11:03:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001205","title":"Onco-exaptation of an Endogenous Retroviral LTR Drives IRF5 Expression in Hodgkin Lymphoma","description":"The transcription factor interferon regulatory factor 5 (IRF5) is upregulated in Hodgkin lymphoma (HL) and a key regulator of the aberrant transcriptome characteristic of this disease. Here we show that IRF5 upregulation in HL is driven by transcriptional activation of a normally dormant endogenous retroviral LOR1a long terminal repeat (LTR) upstream of IRF5. Specifically, through screening of RNA-seq libraries, we detected LTR-IRF5 chimeric transcripts in multiple HL cell lines but not in normal B-cell controls. In HL, the LTR was in an open and hypomethylated epigenetic state and we further show the LTR is the site of transcriptional initiation. Among HL cell lines, usage of the LTR promoter strongly correlates with overall levels of IRF5 mRNA and protein, indicating that LTR transcriptional awakening is a major contributor to IRF5 upregulation in HL. Taken together, oncogenic IRF5 overexpression in HL is the result of a specific LTR transcriptional activation. We propose that such LTR derepression is a distinct mechanism of oncogene activation (“onco-exaptation”) and that such a mechanism warrants further investigation in molecular and cancer research.","abstract":"The transcription factor interferon regulatory factor 5 (IRF5) is upregulated in Hodgkin lymphoma (HL) and a key regulator of the aberrant transcriptome characteristic of this disease. Here we show that IRF5 upregulation in HL is driven by transcriptional activation of a normally dormant endogenous retroviral LOR1a long terminal repeat (LTR) upstream of IRF5. Specifically, through screening of RNA-seq libraries, we detected LTR-IRF5 chimeric transcripts in multiple HL cell lines but not in normal B-cell controls. In HL, the LTR was in an open and hypomethylated epigenetic state and we further show the LTR is the site of transcriptional initiation. Among HL cell lines, usage of the LTR promoter strongly correlates with overall levels of IRF5 mRNA and protein, indicating that LTR transcriptional awakening is a major contributor to IRF5 upregulation in HL. Taken together, oncogenic IRF5 overexpression in HL is the result of a specific LTR transcriptional activation. We propose that such LTR derepression is a distinct mechanism of oncogene activation (“onco-exaptation”) and that such a mechanism warrants further investigation in molecular and cancer research.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-26T17:43:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001206","title":"Illumina HumanCoreExome genotyping data from the British Society for Surgery of the Hand Genetics of Dupuytren’s Disease consortium (BSSH-GODD consortium) collection","description":"Dupuytren's Disease (DD - OMIM126900) is the most common heritable disorder of connective tissue. It is a fibroproliferative disorder of the palmer fascia, causing flexion contractures of affected digits. DD affects men more commonly than women. DD is an archetypal complex disease, with multiple genetic and environmental factors affecting the final expression of the disease phenotype. The incidence increases with age, and the prevalence of DD is therefore increasing as the UK population ages. Half of all patients present before age 60. DD causes significant functional impairment, and severe contractures can lead to permanent disability. The mainstay of current treatment is surgery, but recurrence and complications are both high. For severe contractures, the only suitable treatment option is amputation. The direct costs to the NHS are high, and underestimate the true economic costs to society. We collected salivary samples from adults in the UK who have had surgery for DD. We have genotyped these samples using the Illumina HumanCoreExome Beadchips.  https://research.ndorms.ox.ac.uk/public/dupuytrens/what-is-dupuytrens-disease/","abstract":"Dupuytren's Disease (DD - OMIM126900) is the most common heritable disorder of connective tissue. It is a fibroproliferative disorder of the palmer fascia, causing flexion contractures of affected digits. DD affects men more commonly than women. DD is an archetypal complex disease, with multiple genetic and environmental factors affecting the final expression of the disease phenotype. The incidence increases with age, and the prevalence of DD is therefore increasing as the UK population ages. Half of all patients present before age 60. DD causes significant functional impairment, and severe contractures can lead to permanent disability. The mainstay of current treatment is surgery, but recurrence and complications are both high. For severe contractures, the only suitable treatment option is amputation. The direct costs to the NHS are high, and underestimate the true economic costs to society. We collected salivary samples from adults in the UK who have had surgery for DD. We have genotyped these samples using the Illumina HumanCoreExome Beadchips.  https://research.ndorms.ox.ac.uk/public/dupuytrens/what-is-dupuytrens-disease/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-27T11:00:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001207","title":"15x_WGS_HELIC_MANOLIS_","description":"15x whole genome sequencing in samples from the Cretan Greek isolate collection HELIC MANOLIS","abstract":"15x whole genome sequencing in individuals from the HELlenic Isolated Cohorts study (HELIC) Minoan isolates (MANOLIS) cohort. Individuals are from the mountainous Mylopotamos villages on the island of Crete.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-27T11:40:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001208","title":"15x_WGS_HELIC_Pomak","description":"15x whole genome sequencing in samples from the Greek isolated collection HELIC Pomak.","abstract":"15x whole genome sequencing in individuals from the HELlenic Isolated Cohorts study (HELIC) in the Pomak villages, a set of religiously isolated mountainous villages in the in the regional unit of Xanthi in the North of Greece.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001209","title":"Anaplastic oligodendroglioma exome and RNA sequencing data","description":"Anaplastic oligodendrogliomas (AOs) are rare primary brain tumors which are generally incurable, with heterogeneous prognosis and few treatment targets identified. Most oligodendrogliomas have chromosome 1p/19q co-deletion and IDH mutation. We analyzed 51 AOs by whole-exome sequencing, identifying previously reported frequent somatic mutations in CIC and FUBP1. We also identified recurrent mutations in TCF12 and in an additional series of 83 AO. Overall 7.5% of AO are mutated for TCF12, which encodes an oligodendrocyte-related transcription factor. 80% of TCF12 mutations identified were in either the bHLH domain, which is important for TCF12 function as a transcription factor, or were frame shift mutations leading to TCF12 truncated for this domain. We show that these mutations compromise TCF12 transcriptional activity and are associated with a more aggressive tumor type. Our analysis provides further insights into the unique and shared pathways driving AO.","abstract":"Anaplastic oligodendrogliomas (AOs) are rare primary brain tumors which are generally incurable, with heterogeneous prognosis and few treatment targets identified. Most oligodendrogliomas have chromosome 1p/19q co-deletion and IDH mutation. We analyzed 51 AOs by whole-exome sequencing, identifying previously reported frequent somatic mutations in CIC and FUBP1. We also identified recurrent mutations in TCF12 and in an additional series of 83 AO. Overall 7.5% of AO are mutated for TCF12, which encodes an oligodendrocyte-related transcription factor. 80% of TCF12 mutations identified were in either the bHLH domain, which is important for TCF12 function as a transcription factor, or were frame shift mutations leading to TCF12 truncated for this domain. We show that these mutations compromise TCF12 transcriptional activity and are associated with a more aggressive tumor type. Our analysis provides further insights into the unique and shared pathways driving AO.","study_type":"Metagenomics","pubmed_ids":[26068201],"external_links":null,"is_released":true,"released_date":"2015-03-27T16:10:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001210","title":"Whole Genome sequencing of adult T-cell leukemia/lymphoma","description":"Whole Genome sequencing of a single adult T-cell leukemia/lymphoma case","abstract":"Whole Genome sequencing of a single adult T-cell leukemia/lymphoma case","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-30T07:37:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001211","title":"EGA Test Study","description":"Test","abstract":"Test","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001212","title":"Pilot_experiment_on_functional_genomics_in_osteoarthritis","description":"The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of large joint (hip and knee) osteoarthritis which culminates in the need for total joint replacement (TJR). In this pilot we will assess the feasibility of the approach in the relevant tissue. We will obtain diseased and non-diseased tissue (cartilage and endochondral bone) following TJR, coupled with a blood sample, from 12 patients. We will generate genotype data on the HumanCoreExome array and will characterise the 12 pairs of diseased and non-diseased tissue samples in terms of methylation (Illumina 450k array), transcription (RNASeq) and expression (quantitative proteomics). The pilot will help assess the feasibility of isolating sufficient levels of starting material for the different approaches, and will instigate the development of analytical approaches to synthesising the resulting data. If successful, it is envisaged that we will proceed with expanding the work to 500 patients in the first year, with a target total sample size of 3,000 in the longer term. The key collaborators in this work are Mark Wilkinson (Sheffield) and Jyoti Choudhary","abstract":"The aim of this work was to apply an integrated systems approach to understand the biological underpinnings of knee osteoarthritis which culminates in the need for total joint replacement (TJR). We obtained diseased and non-diseased cartilage following TJR, coupled with a blood sample, from 12 patients. We generated genotype data on the HumanCoreExome array and characterised the 12 pairs of diseased and non-diseased tissue samples in terms of methylation (Illumina 450k array).","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-30T12:21:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001213","title":"Pilot_experiment_on_functional_genomics_in_osteoarthritis","description":"The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of large joint (hip and knee) osteoarthritis which culminates in the need for total joint replacement (TJR). In this pilot we will assess the feasibility of the approach in the relevant tissue. We will obtain diseased and non-diseased tissue (cartilage and endochondral bone) following TJR, coupled with a blood sample, from 12 patients. We will generate genotype data on the HumanCoreExome array and will characterise the 12 pairs of diseased and non-diseased tissue samples in terms of methylation (Illumina 450k array), transcription (RNASeq) and expression (quantitative proteomics). The pilot will help assess the feasibility of isolating sufficient levels of starting material for the different approaches, and will instigate the development of analytical approaches to synthesising the resulting data. If successful, it is envisaged that we will proceed with expanding the work to 500 patients in the first year, with a target total sample size of 3,000 in the longer term. The key collaborators in this work are Mark Wilkinson (Sheffield) and Jyoti Choudhary","abstract":"The aim of this work was to apply an integrated systems approach to understand the biological underpinnings of knee osteoarthritis which culminates in the need for total joint replacement (TJR). We obtained diseased and non-diseased cartilage following TJR, coupled with a blood sample, from 12 patients. We generated genotype data on the HumanCoreExome array and characterised the 12 pairs of diseased and non-diseased tissue samples in terms of methylation (Illumina 450k array).","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-03-30T12:23:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001214","title":"Whole genome and transcriptome analysis of anaplastic thyroid carcinoma","description":"Whole genome and transcriptome analysis of anaplastic thyroid carcinoma","abstract":"Whole genome and transcriptome analysis of anaplastic thyroid carcinoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-04-03T00:08:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001215","title":"We sequenced whole genomes of 12 tumor-blood pairs of nasopharyngeal carcinomas(NPC).","description":"We sequenced whole genomes of 12 tumor-blood pairs of nasopharyngeal carcinomas","abstract":"We sequenced whole genomes of 12 tumor-blood pairs of nasopharyngeal carcinomas","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001216","title":"Identification of Somatic Alterations in Stage I Lung Adenocarcinomas by Next-generation Sequencing","description":"Identification of Somatic Alterations in Stage I Lung Adenocarcinomas by NGS","abstract":"Identification of Somatic Alterations in Stage I Lung Adenocarcinomas by NGS","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001217","title":"Whole exome sequencing discovered recurrent mutations in RECQL in Polish and French Canadian populations. Follow-ip studies suggested RECQL as a new breast cancer susceptibility gene.","description":"Several moderate and high risk breast cancer susceptibility genes have been discovered, but more are likely to exist. To discover new breast cancer susceptibility genes, we used two populations (Poland and Quebec, Canada) and applied whole exome sequencing in a discovery phase (n = 195), followed by validation of these findings. We identified rare recurrent RECQL mutations in each population. In Quebec, 7 of 1,013 higher-risk breast cancer cases and 1 of 7,136 newborns carried the c.634C&gt;T (p.Arg215Ter) variant (p = 0.00004). In Poland, 30 of 13,136 unselected breast cancer cases and 2 of 4,702 controls carried the c.1667_1667+3delAGTA, p.K555delinsMYKLIHYSFR variant (p = 0.008). RECQL is implicated in resolving stalled DNA replication forks to prevent double-stranded DNA (dsDNA) breaks; this function is related to that of other known breast cancer genes, many of which are involved in repairing dsDNA breaks. We conclude that RECQL is a breast cancer susceptibility gene.","abstract":"Several moderate and high risk breast cancer susceptibility genes have been discovered, but more are likely to exist. To discover new breast cancer susceptibility genes, we used two populations (Poland and Quebec, Canada) and applied whole exome sequencing in a discovery phase (n = 195), followed by validation of these findings. We identified rare recurrent RECQL mutations in each population. In Quebec, 7 of 1,013 higher-risk breast cancer cases and 1 of 7,136 newborns carried the c.634C&gt;T (p.Arg215Ter) variant (p = 0.00004). In Poland, 30 of 13,136 unselected breast cancer cases and 2 of 4,702 controls carried the c.1667_1667+3delAGTA, p.K555delinsMYKLIHYSFR variant (p = 0.008). RECQL is implicated in resolving stalled DNA replication forks to prevent double-stranded DNA (dsDNA) breaks; this function is related to that of other known breast cancer genes, many of which are involved in repairing dsDNA breaks. We conclude that RECQL is a breast cancer susceptibility gene.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001218","title":"Validation_for_human_early_embryonic_substitutions_","description":"PCR and MiSeq validation for early embryonic substitution candidates from 400 Breast cancer patients","abstract":"We identified 1,345 somatic mutations in normal tissues. We aims to validate them using amplicon MiSeq sequencing.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-04-10T15:14:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001219","title":"Deconvolution","description":"Deconvolution","abstract":"Deconvolution","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-04-14T01:03:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001220","title":"'Aberrant androgen receptor signaling disclosed by integrated genomic analysis in primary prostate cancer'","description":"\"Prostate cancer is the second most frequent cancer among men worldwide. The androgen signaling pathway plays a central role in tumor development and progression. The androgen receptor (AR), orchestrating differentiation in the normal prostate, turns into an oncogenic driver in prostate tumors. We applied an integrative genomics approach to study the AR signaling pathway and the complex interplay between different genetic levels in primary prostate cancer. We combined genomic mutations, copy number alterations (CNA) and differential gene expression in order to provide tools to improve our understanding of pathogenic AR signaling in prostate cancer. We generated genomic information on 1048 signaling pathway genes of 32 prostate cancers and corresponding normal tissues and used this data in combination with gene expression data on the same tissues. We find genes predominantly affected by CNAs such as PTEN, SORBS3 and COPS5, whereas for others we find regulations on multiple levels. PMEPA1 for example contains SNAs in TMPRSS2-ERG fusiongene positive patients, whereas in fusiongene-negative tumors we primarily find CNAs. Thus, for a comprehensive understanding of pathogenic processes it is required to simultaneously investigate different levels of genomic information.\"","abstract":"\"Prostate cancer is the second most frequent cancer among men worldwide. The androgen signaling pathway plays a central role in tumor development and progression. The androgen receptor (AR), orchestrating differentiation in the normal prostate, turns into an oncogenic driver in prostate tumors. We applied an integrative genomics approach to study the AR signaling pathway and the complex interplay between different genetic levels in primary prostate cancer. We combined genomic mutations, copy number alterations (CNA) and differential gene expression in order to provide tools to improve our understanding of pathogenic AR signaling in prostate cancer. We generated genomic information on 1048 signaling pathway genes of 32 prostate cancers and corresponding normal tissues and used this data in combination with gene expression data on the same tissues. We find genes predominantly affected by CNAs such as PTEN, SORBS3 and COPS5, whereas for others we find regulations on multiple levels. PMEPA1 for example contains SNAs in TMPRSS2-ERG fusiongene positive patients, whereas in fusiongene-negative tumors we primarily find CNAs. Thus, for a comprehensive understanding of pathogenic processes it is required to simultaneously investigate different levels of genomic information.\"","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001221","title":"Mutational_landscape_induced_by_ionizing_radiation_in_human_cells","description":"Genome-wide analysis of mutations induced by ionizing radiation in human cells in different conditions.","abstract":"Ionizing radiation (IR) is a well known mutagen and it is used to treat a broad range of cancers. However, the exact nature and the distribution of IR-induced mutations has not yet been characterized. Here, we have derived two clonal RPE-I cell lines; arrested them in G0; and irradiated them with known doses of X-rays. After irradiation, single survivor clones have been picked and expanded. We now aim to define their mutational spectra by whole genome sequencing and bioinformatics analyses. We will also evaluate the impact of ATM (a key factor in the DNA damage response) inhibition on the mutations induced by IR.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001222","title":"MEK162_study","description":"To analyse pre biopsy samples from the  MEK162 clinical trial and correlate a targeted capture of known cancer genes with response parameters to MEK inhibition in MEK inhibitor treated RAS mutant Melanoma.","abstract":"Recent data has given insight into the potential  utility of treatment of patients with RAS driven metastatic melanoma with a MEK inhibitor .    However from recent trial data it is clear that response is variable amongst this patient population.   We propose that response may be determined by underlying genomic  diversity  and that by understanding this and correlating genetic factors with response dynamics in MEK inhibitor treated patients we may understand novel subgroups in which MEK  inhibition is optimal, and potentially understand intrinsic resistance to this approach.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001223","title":"LINE_luminal_breast_cancer_Neoadjuvant_Chemotherapy_Study","description":"A targeted gene screen of 365 known cancer genes in luminal breast cancer samples pre-chemotherapy and at resection post-chemotherapy to evalaute clonal expansion of chemotherapy cancer cells.","abstract":"Although the largest number of breast cancer deaths occur in patients presenting with luminal cancer (ER-positive and HER2-negative) and this is associated with failure to achieve a pathological complete response (pCR) after chemotherapy. The LINE study has collected tumour samples prior to neoadjuvant chemotherapy and then following surgical resection of the luminal breast cancer. We propose using a targeted panel of 365 cancer genes to assess as a pilot the feasibility of NGS in FFPE samples and to assess whether there is any evidence of a clonal expansion of chemotherapy resistant cells through analysis of the variant allelic fractions in matched the pre- and post-chemotherapy samples. We will also look at whether there are differences in the patterns of mutations in the pre-chemotherapy samples from patients on the pCR and non-pCR groups.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-04-15T12:13:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001224","title":"WTCCC__Exome_Chip_AITD","description":"Following several rounds of GWA scans and subsequent meta-analyses of results we have identified multiple risk loci for many common diseases. However, in most instances the implicated common variants identified so far explain only a modest fraction of the genetic risk. In parallel to our efforts to identify the causative variants in the known loci it is necessary to assess the full spectrum of sequence variants for disease risk and in particular low frequency and rare variants that have not been tested in a comprehensive way so far. To this end an international effort by investigators who have performed whole exome sequencing in circa 12,000 individuals have made possible to assemble a set of ~250,000 exonic variants of low frequency – defined as seen in at least two studies and a minimum of three individuals (non-sysnonymous) or two individuals for SNPs altering splice sites / stop codons. Adequately powered association studies to test low frequency variants for association to disease risk are still very expensive to be conducted by whole exome sequencing. The exome chip provides a cost efficient way to undertake such an experiment and the WTCCC will be applying this approach to eight diseases, type 1 and type 2 diabetes, coronary artery disease, hypertension, multiple sclerosis, rheumatoid arthritis, bipolar, and ankylosing spondylitis. The first objective will be to generate a large set of at least 10,000 common UK controls as analysis of lower frequency variants will require large sample sizes. Each disease group within the WTCCC has established international partnerships to proceed with assembling equally large number of cases. To maximise returns WTCCC would like to utilise controls with rich phenotypic information and appropriate permissions to have genotypic data accessed by bona fide researchers through a public repository such as the EGA.WTCCC will fund typing of 21,600 samples in total using the exome array. We request capacity to type 14,700 of these samples in house  - samples will include the 1958 British Birth Cohort (6500), Cambridge Bioresource (2200), and case series from CAD, HT, MS, RA (1500 each).  We note that controls from the Oxford Biobank (2700) will by typed in Oxford, BD cases at the Broad whereas AS cases and controls will be typed Brisbane. Analytically we want to involve the HGI group to perform co-clustering of data sets (including additional samples) and calling of low frequency variants which will be one of the challenges in this project.  The project should be seen in the context of a broader UK effort on the exome chip to involve 60-70K samples. My group will subsequently focus on the analysis of the CAD cases as well as cardiovascular triats such as lipids.","abstract":"Following several rounds of GWA scans and subsequent meta-analyses of results we have identified multiple risk loci for many common diseases. However, in most instances the implicated common variants identified so far explain only a modest fraction of the genetic risk. In parallel to our efforts to identify the causative variants in the known loci it is necessary to assess the full spectrum of sequence variants for disease risk and in particular low frequency and rare variants that have not been tested in a comprehensive way so far. To this end an international effort by investigators who have performed whole exome sequencing in circa 12,000 individuals have made possible to assemble a set of ~250,000 exonic variants of low frequency – defined as seen in at least two studies and a minimum of three individuals (non-sysnonymous) or two individuals for SNPs altering splice sites / stop codons. Adequately powered association studies to test low frequency variants for association to disease risk are still very expensive to be conducted by whole exome sequencing. The exome chip provides a cost efficient way to undertake such an experiment and the WTCCC will be applying this approach to eight diseases, type 1 and type 2 diabetes, coronary artery disease, hypertension, multiple sclerosis, rheumatoid arthritis, bipolar, and ankylosing spondylitis. The first objective will be to generate a large set of at least 10,000 common UK controls as analysis of lower frequency variants will require large sample sizes. Each disease group within the WTCCC has established international partnerships to proceed with assembling equally large number of cases. To maximise returns WTCCC would like to utilise controls with rich phenotypic information and appropriate permissions to have genotypic data accessed by bona fide researchers through a public repository such as the EGA.WTCCC will fund typing of 21,600 samples in total using the exome array. We request capacity to type 14,700 of these samples in house  - samples will include the 1958 British Birth Cohort (6500), Cambridge Bioresource (2200), and case series from CAD, HT, MS, RA (1500 each).  We note that controls from the Oxford Biobank (2700) will by typed in Oxford, BD cases at the Broad whereas AS cases and controls will be typed Brisbane. Analytically we want to involve the HGI group to perform co-clustering of data sets (including additional samples) and calling of low frequency variants which will be one of the challenges in this project.  The project should be seen in the context of a broader UK effort on the exome chip to involve 60-70K samples. My group will subsequently focus on the analysis of the CAD cases as well as cardiovascular triats such as lipids.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001225","title":"Analysis_of_lowfrequency_coding_variants_in_cardiometabolic_traits","description":"The new round of meta-analysis in CAD/MI undertaken currently by CARDIoGRAMplusC4D which I am leading, has brought the total number of confirmed genome wide significant loci to 44 but as seen for other common diseases they collectively explain a modest  fraction of the genetic component. We have start seeing evidence of multiple independent variants among several of the 26 CAD loci that are undergoing fine mappping. Similarly in the lipid consortium a further 88 new loci have been identified in the current round bringing the total to over 180. Low frequency variants on the Metabochip were selected from an early release of the 1000 genomes project and therefore assessing the contribution of such variants to disease risk is incomplete.Based on a SNP set derived from 12,000 exomes and whole genomes an iSELECT array of circa 250,000 markers is been generated. The array will include mainly exonic SNPs (~246K) of which ~145 are non-synonymous. Inclusion criteria consisted of a SNP to be seen in at least 3 individuals and across at least two data sets.  Although most of the contributed data sets correspond to healthy individuals there was inclusion of variants derived from a few disease oriented exome studies one of which is the NHLBI funded effort on myocardial infarction. In addition, the exome array will include the most up to date GWA / metabochip hits from several consortia including GLGC( lipid) and CARDIoGRAMplusC4D (coronary artery disease (CAD)). The array includes some generic marker sets e.g. HLA, mitDNA, Y chromosome etc.The exome array provides an excellent opportunity to interrogate in a comprehensive way coding variants at the genome level including low frequency ones at a rather low cost. Availability of large sample collections will be essential to assess the impact of low frequency variants to disease risk. I am proposing a study to test the exome marker set for lipids and CAD/MI in 16000 people (5500 cases and 10,000 (possibly more) controls).I will seek validation of initial findings through CARDIoGRAMplusC4D which comprises over 60,000 CAD/MI cases and 120,000 controlsThe study will combine data generated as part of the WTCCC /UK exome consortium with data on 5000 samples (to include 4000 CAD/MI cases) for which I am requesting core funding under Aim 1.1 of Project 3: Genetics of Common Diseases. The 5000 samples include (i) 2000 CAD/MI cases from the EPIC-Norfolk cohort (ii) 1000 CAD/MI cases from the BHF collection and (iii) our Greek cohort THISEAS (1000 cases and 1000 controls) which has data on multiple cardiometabolic traits.  UK controls will come from the UK exome consortium effort to build a large UK control set. This effort which includes WTCCC investigators and a few other UK groups (cancer, lung function, Alzheimer's) aims to type up to 15,000 controls - WTCCC is funding 9,500 of the controls.  The selection of UK control sets is currently under discussion but one of the criteria is availability of other phenotypes and the 1958 British Birth Cohort (6500 samples) had unanimous support. Other relevant cohorts are: UKBloodService (3K), GRAPHIC (2K), Cambridge bioresource (8K), Oxford Biobank (3K), and Twins UK (6K). Finally, WTCCC is funding 1500 cases per participating disease phenotype; the 1500 CAD allocation (represented by Nilesh Samani and myself) will bring the total number of cases to 5500.Such a data set will not only drive the initial analysis round but will allow participation in subsequent meta-analyses as well as contributions in parallel international efforts e.g haematological and anthropometric traits, blood pressure, etc","abstract":"The new round of meta-analysis in CAD/MI undertaken currently by CARDIoGRAMplusC4D which I am leading, has brought the total number of confirmed genome wide significant loci to 44 but as seen for other common diseases they collectively explain a modest  fraction of the genetic component. We have start seeing evidence of multiple independent variants among several of the 26 CAD loci that are undergoing fine mappping. Similarly in the lipid consortium a further 88 new loci have been identified in the current round bringing the total to over 180. Low frequency variants on the Metabochip were selected from an early release of the 1000 genomes project and therefore assessing the contribution of such variants to disease risk is incomplete.Based on a SNP set derived from 12,000 exomes and whole genomes an iSELECT array of circa 250,000 markers is been generated. The array will include mainly exonic SNPs (~246K) of which ~145 are non-synonymous. Inclusion criteria consisted of a SNP to be seen in at least 3 individuals and across at least two data sets.  Although most of the contributed data sets correspond to healthy individuals there was inclusion of variants derived from a few disease oriented exome studies one of which is the NHLBI funded effort on myocardial infarction. In addition, the exome array will include the most up to date GWA / metabochip hits from several consortia including GLGC( lipid) and CARDIoGRAMplusC4D (coronary artery disease (CAD)). The array includes some generic marker sets e.g. HLA, mitDNA, Y chromosome etc.The exome array provides an excellent opportunity to interrogate in a comprehensive way coding variants at the genome level including low frequency ones at a rather low cost. Availability of large sample collections will be essential to assess the impact of low frequency variants to disease risk. I am proposing a study to test the exome marker set for lipids and CAD/MI in 16000 people (5500 cases and 10,000 (possibly more) controls).I will seek validation of initial findings through CARDIoGRAMplusC4D which comprises over 60,000 CAD/MI cases and 120,000 controlsThe study will combine data generated as part of the WTCCC /UK exome consortium with data on 5000 samples (to include 4000 CAD/MI cases) for which I am requesting core funding under Aim 1.1 of Project 3: Genetics of Common Diseases. The 5000 samples include (i) 2000 CAD/MI cases from the EPIC-Norfolk cohort (ii) 1000 CAD/MI cases from the BHF collection and (iii) our Greek cohort THISEAS (1000 cases and 1000 controls) which has data on multiple cardiometabolic traits.  UK controls will come from the UK exome consortium effort to build a large UK control set. This effort which includes WTCCC investigators and a few other UK groups (cancer, lung function, Alzheimer's) aims to type up to 15,000 controls - WTCCC is funding 9,500 of the controls.  The selection of UK control sets is currently under discussion but one of the criteria is availability of other phenotypes and the 1958 British Birth Cohort (6500 samples) had unanimous support. Other relevant cohorts are: UKBloodService (3K), GRAPHIC (2K), Cambridge bioresource (8K), Oxford Biobank (3K), and Twins UK (6K). Finally, WTCCC is funding 1500 cases per participating disease phenotype; the 1500 CAD allocation (represented by Nilesh Samani and myself) will bring the total number of cases to 5500.Such a data set will not only drive the initial analysis round but will allow participation in subsequent meta-analyses as well as contributions in parallel international efforts e.g haematological and anthropometric traits, blood pressure, etc","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001226","title":"Analysis_of_lowfrequency_coding_variants_in_cardiometabolic_traits___epic","description":"The new round of meta-analysis in CAD/MI undertaken currently by CARDIoGRAMplusC4D which I am leading, has brought the total number of confirmed genome wide significant loci to 44 but as seen for other common diseases they collectively explain a modest  fraction of the genetic component. We have start seeing evidence of multiple independent variants among several of the 26 CAD loci that are undergoing fine mappping. Similarly in the lipid consortium a further 88 new loci have been identified in the current round bringing the total to over 180. Low frequency variants on the Metabochip were selected from an early release of the 1000 genomes project and therefore assessing the contribution of such variants to disease risk is incomplete.Based on a SNP set derived from 12,000 exomes and whole genomes an iSELECT array of circa 250,000 markers is been generated. The array will include mainly exonic SNPs (~246K) of which ~145 are non-synonymous. Inclusion criteria consisted of a SNP to be seen in at least 3 individuals and across at least two data sets.  Although most of the contributed data sets correspond to healthy individuals there was inclusion of variants derived from a few disease oriented exome studies one of which is the NHLBI funded effort on myocardial infarction. In addition, the exome array will include the most up to date GWA / metabochip hits from several consortia including GLGC( lipid) and CARDIoGRAMplusC4D (coronary artery disease (CAD)). The array includes some generic marker sets e.g. HLA, mitDNA, Y chromosome etc.The exome array provides an excellent opportunity to interrogate in a comprehensive way coding variants at the genome level including low frequency ones at a rather low cost. Availability of large sample collections will be essential to assess the impact of low frequency variants to disease risk. I am proposing a study to test the exome marker set for lipids and CAD/MI in 16000 people (5500 cases and 10,000 (possibly more) controls).I will seek validation of initial findings through CARDIoGRAMplusC4D which comprises over 60,000 CAD/MI cases and 120,000 controlsThe study will combine data generated as part of the WTCCC /UK exome consortium with data on 5000 samples (to include 4000 CAD/MI cases) for which I am requesting core funding under Aim 1.1 of Project 3: Genetics of Common Diseases. The 5000 samples include (i) 2000 CAD/MI cases from the EPIC-Norfolk cohort (ii) 1000 CAD/MI cases from the BHF collection and (iii) our Greek cohort THISEAS (1000 cases and 1000 controls) which has data on multiple cardiometabolic traits.  UK controls will come from the UK exome consortium effort to build a large UK control set. This effort which includes WTCCC investigators and a few other UK groups (cancer, lung function, Alzheimer's) aims to type up to 15,000 controls - WTCCC is funding 9,500 of the controls.  The selection of UK control sets is currently under discussion but one of the criteria is availability of other phenotypes and the 1958 British Birth Cohort (6500 samples) had unanimous support. Other relevant cohorts are: UKBloodService (3K), GRAPHIC (2K), Cambridge bioresource (8K), Oxford Biobank (3K), and Twins UK (6K). Finally, WTCCC is funding 1500 cases per participating disease phenotype; the 1500 CAD allocation (represented by Nilesh Samani and myself) will bring the total number of cases to 5500.Such a data set will not only drive the initial analysis round but will allow participation in subsequent meta-analyses as well as contributions in parallel international efforts e.g haematological and anthropometric traits, blood pressure, etc","abstract":"The new round of meta-analysis in CAD/MI undertaken currently by CARDIoGRAMplusC4D which I am leading, has brought the total number of confirmed genome wide significant loci to 44 but as seen for other common diseases they collectively explain a modest  fraction of the genetic component. We have start seeing evidence of multiple independent variants among several of the 26 CAD loci that are undergoing fine mappping. Similarly in the lipid consortium a further 88 new loci have been identified in the current round bringing the total to over 180. Low frequency variants on the Metabochip were selected from an early release of the 1000 genomes project and therefore assessing the contribution of such variants to disease risk is incomplete.Based on a SNP set derived from 12,000 exomes and whole genomes an iSELECT array of circa 250,000 markers is been generated. The array will include mainly exonic SNPs (~246K) of which ~145 are non-synonymous. Inclusion criteria consisted of a SNP to be seen in at least 3 individuals and across at least two data sets.  Although most of the contributed data sets correspond to healthy individuals there was inclusion of variants derived from a few disease oriented exome studies one of which is the NHLBI funded effort on myocardial infarction. In addition, the exome array will include the most up to date GWA / metabochip hits from several consortia including GLGC( lipid) and CARDIoGRAMplusC4D (coronary artery disease (CAD)). The array includes some generic marker sets e.g. HLA, mitDNA, Y chromosome etc.The exome array provides an excellent opportunity to interrogate in a comprehensive way coding variants at the genome level including low frequency ones at a rather low cost. Availability of large sample collections will be essential to assess the impact of low frequency variants to disease risk. I am proposing a study to test the exome marker set for lipids and CAD/MI in 16000 people (5500 cases and 10,000 (possibly more) controls).I will seek validation of initial findings through CARDIoGRAMplusC4D which comprises over 60,000 CAD/MI cases and 120,000 controlsThe study will combine data generated as part of the WTCCC /UK exome consortium with data on 5000 samples (to include 4000 CAD/MI cases) for which I am requesting core funding under Aim 1.1 of Project 3: Genetics of Common Diseases. The 5000 samples include (i) 2000 CAD/MI cases from the EPIC-Norfolk cohort (ii) 1000 CAD/MI cases from the BHF collection and (iii) our Greek cohort THISEAS (1000 cases and 1000 controls) which has data on multiple cardiometabolic traits.  UK controls will come from the UK exome consortium effort to build a large UK control set. This effort which includes WTCCC investigators and a few other UK groups (cancer, lung function, Alzheimer's) aims to type up to 15,000 controls - WTCCC is funding 9,500 of the controls.  The selection of UK control sets is currently under discussion but one of the criteria is availability of other phenotypes and the 1958 British Birth Cohort (6500 samples) had unanimous support. Other relevant cohorts are: UKBloodService (3K), GRAPHIC (2K), Cambridge bioresource (8K), Oxford Biobank (3K), and Twins UK (6K). Finally, WTCCC is funding 1500 cases per participating disease phenotype; the 1500 CAD allocation (represented by Nilesh Samani and myself) will bring the total number of cases to 5500.Such a data set will not only drive the initial analysis round but will allow participation in subsequent meta-analyses as well as contributions in parallel international efforts e.g haematological and anthropometric traits, blood pressure, etc","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001227","title":"Immunochip_study_of_WTCCC1_Gambian_Tuberculosis_case_control_samples","description":"Immunochip study of WTCCC1 Gambian Tuberculosis case control samples","abstract":"Immunochip study of WTCCC1 Gambian Tuberculosis case control samples","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001228","title":"Protein_QTL_analysis_in_79_French_families_from_the_Stanislas_cohort","description":"Recent GWAS studies have made extensive use of large eQTL data sets to functionally annotate index SNPs. With a large number of association signals located outside coding regions there has been an intenese search among sequence variants affecting gene expression at the transcriptional level. However, little progress has been made in mapping regulatory variants that affect protein levels at the translational or post-translational level. It is now possible to undertake a protein QTL scan for focused sets of e.g. oxidized proteins by mass spectrometry. We have established a collaboration with a longitudinal, family-based study in France, the Stanislas cohort, which comprises circa 1000 nuclear families (4,295 individuals) and has follow up data for 10 years (three visits). We propose a pilot protein QTL study integrated with transcriptomic and methylation data in a focus set of 257 subjects from 79 families for which quantitative proteomic data will be measured for a set of 100 proteins in PBMCs. For this purpose we would like to use the new Illumina biobank chip and also generate DNA methylation data with Illumina’s 450K array. Transcriptomic data will be generated in Nancy. The aim of the study is to identify protein QTLs and correlate them with eQTL and metQTL data. Available phenotypic information includes gender, age, weight, height, BMI, waist circumference, hip circumference, waist/hip ratio, systolic blood pressure, diastolic blood pressure, pulse pressure, total cholesterol, triglycerides, HDL, LDL, blood glucose, total protein and albumin, lipoprotein lipase a, apolipoprotein A1, apolipoproetein B, apoliprotein E, CRP, osrosomucoid, haptoglobin, smoking and alcohol intake .","abstract":"Recent GWAS studies have made extensive use of large eQTL data sets to functionally annotate index SNPs. With a large number of association signals located outside coding regions there has been an intenese search among sequence variants affecting gene expression at the transcriptional level. However, little progress has been made in mapping regulatory variants that affect protein levels at the translational or post-translational level. It is now possible to undertake a protein QTL scan for focused sets of e.g. oxidized proteins by mass spectrometry. We have established a collaboration with a longitudinal, family-based study in France, the Stanislas cohort, which comprises circa 1000 nuclear families (4,295 individuals) and has follow up data for 10 years (three visits). We propose a pilot protein QTL study integrated with transcriptomic and methylation data in a focus set of 257 subjects from 79 families for which quantitative proteomic data will be measured for a set of 100 proteins in PBMCs. For this purpose we would like to use the new Illumina biobank chip and also generate DNA methylation data with Illumina’s 450K array. Transcriptomic data will be generated in Nancy. The aim of the study is to identify protein QTLs and correlate them with eQTL and metQTL data. Available phenotypic information includes gender, age, weight, height, BMI, waist circumference, hip circumference, waist/hip ratio, systolic blood pressure, diastolic blood pressure, pulse pressure, total cholesterol, triglycerides, HDL, LDL, blood glucose, total protein and albumin, lipoprotein lipase a, apolipoprotein A1, apolipoproetein B, apoliprotein E, CRP, osrosomucoid, haptoglobin, smoking and alcohol intake .","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001229","title":"Left_main_coronary_artery_disease","description":"Greater than 50% narrowing of the left main coronary artery is found in less than 4% of all patientswho undergo coronary arteriography. Most patients with left main coronary artery disease (LMCAD)are symptomatic and at high risk of cardiovascular events, since occlusion of this vesselcompromises flow to at least 75% of the left ventricle. Healthy siblings of a person with LMCAD are2.5 times more likely to go on to develop some form of heart disease than were siblings of a patientwith heart disease that did not relate to the left main coronary artery. However, little is known as towhether there are specific genetic factors which underlie LMCAD and distinguish it from generalCAD. As part of the THISEAS study we recently recruited 300 patients with proven LMCAD andpropose to profile them using the HumanOmniExpressExome. We will then undertake a case controlanalysis of LMCAD patients vs CAD patients without LMCAD - in THISEAS we have available GWASdata for ~800 CAD patients without LMCAD. In parallel, we will assess the 46 known CAD risk loci forinvolvemnt in LMCAD pathogenesis by analysing the LMCAD cases against non disease controls fromTHISEAS. We are in the process of contacting members of the CARDIoGRAMplusC4D consortium toassess options for replication of potential findings from the main analysis and have initialconfirmation from a German group that has ~90 LMCAD patients.","abstract":"Greater than 50% narrowing of the left main coronary artery is found in less than 4% of all patientswho undergo coronary arteriography. Most patients with left main coronary artery disease (LMCAD)are symptomatic and at high risk of cardiovascular events, since occlusion of this vesselcompromises flow to at least 75% of the left ventricle. Healthy siblings of a person with LMCAD are2.5 times more likely to go on to develop some form of heart disease than were siblings of a patientwith heart disease that did not relate to the left main coronary artery. However, little is known as towhether there are specific genetic factors which underlie LMCAD and distinguish it from generalCAD. As part of the THISEAS study we recently recruited 300 patients with proven LMCAD andpropose to profile them using the HumanOmniExpressExome. We will then undertake a case controlanalysis of LMCAD patients vs CAD patients without LMCAD - in THISEAS we have available GWASdata for ~800 CAD patients without LMCAD. In parallel, we will assess the 46 known CAD risk loci forinvolvemnt in LMCAD pathogenesis by analysing the LMCAD cases against non disease controls fromTHISEAS. We are in the process of contacting members of the CARDIoGRAMplusC4D consortium toassess options for replication of potential findings from the main analysis and have initialconfirmation from a German group that has ~90 LMCAD patients.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001230","title":"Monocyte_expression_QTL_analysis_in_MI_patients_and_healthy_controls","description":"Based on a case-control design (PROMIS study) we recruited 100 MI patients and 100 non-disease controls for which we isolated RNA from monocytes . RNA-seq has been successfully completed in 165 individuals (30-40 million reads per sample) and we are currently performing expression analysis to look for differentially expressed transcripts including allele specific differences. The other angle of this study is to explore whether eSNPs differ between cases and controls. We have GWAS data for 77of the RNA-sequenced samples and request budget to profile the remaining 88 samples (we will use 96 samples which is the Facility's unit) with Illumina's HumanCoreExome array.","abstract":"Based on a case-control design (PROMIS study) we recruited 100 MI patients and 100 non-disease controls for which we isolated RNA from monocytes . RNA-seq has been successfully completed in 165 individuals (30-40 million reads per sample) and we are currently performing expression analysis to look for differentially expressed transcripts including allele specific differences. The other angle of this study is to explore whether eSNPs differ between cases and controls. We have GWAS data for 77of the RNA-sequenced samples and request budget to profile the remaing 88 samples (we will use 96 samples which is the Facility's unit) with Illumina's HumanCoreExome array.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001231","title":"Yemen_and_Chad_Genotyping","description":"HumanOmni2.5-8 data from Chad and Yemen.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"HumanOmni2.5-8 data from Chad and Yemen","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-04-15T14:49:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001232","title":"Understanding_Society_GWAS","description":"The UK Household Longitudinal Study (Understanding Society https://www.understandingsociety.ac.uk/) aims to create and enhance a resource for a wide range of scientists, both social and biological, by combining the collection of biomarkers and psychosocial information with high quality longitudinal social and economic data about individuals and families.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The UK Household Longitudinal Study (Understanding Society https://www.understandingsociety.ac.uk/) aims to create and enhance a resource for a wide range of scientists, both social and biological, by combining the collection of biomarkers and psychosocial information with high quality longitudinal social and economic data about individuals and families.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-04-16T12:38:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001233","title":"Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells","description":"Mitochondrial genomes are separated from the nuclear genome for most of the cell cycle by the nuclear double membrane, intervening cytoplasm and the mitochondrial double membrane. Despite these physical barriers we show that somatically acquired mitochondrial-nuclear genome fusion sequences are present in cancer cells. Most occur in conjunction with intranuclear genomic rearrangements and the features of the fusion fragments indicate that non-homologous end joining and/or replication-dependent DNA double strand break repair are the dominant mechanism involved. This study includes 12 pairs of whole-genome sequences (tumour and paired-normal), which present somatic mitochondrial DNA integrations in tumour genomes. Reference: Young Seok Ju et al., Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells, Genome Research (2015).","abstract":"Mitochondrial genomes are separated from the nuclear genome for most of the cell cycle by the nuclear double membrane, intervening cytoplasm and the mitochondrial double membrane. Despite these physical barriers we show that somatically acquired mitochondrial-nuclear genome fusion sequences are present in cancer cells. Most occur in conjunction with intranuclear genomic rearrangements and the features of the fusion fragments indicate that non-homologous end joining and/or replication-dependent DNA double strand break repair are the dominant mechanism involved. This study includes 12 pairs of whole-genome sequences (tumour and paired-normal), which present somatic mitochondrial DNA integrations in tumour genomes. Reference: Young Seok Ju et al., Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells, Genome Research (2015).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001234","title":"Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells","description":"Mitochondrial genomes are separated from the nuclear genome for most of the cell cycle by the nuclear double membrane, intervening cytoplasm and the mitochondrial double membrane. Despite these physical barriers we show that somatically acquired mitochondrial-nuclear genome fusion sequences are present in cancer cells. Most occur in conjunction with intranuclear genomic rearrangements and the features of the fusion fragments indicate that non-homologous end joining and/or replication-dependent DNA double strand break repair are the dominant mechanism involved. This study includes 12 pairs of whole-genome sequences (tumour and paired-normal), which present somatic mitochondrial DNA integrations in tumour genomes. Reference: Young Seok Ju et al., Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells, Genome Research (2015).","abstract":"Mitochondrial genomes are separated from the nuclear genome for most of the cell cycle by the nuclear double membrane, intervening cytoplasm and the mitochondrial double membrane. Despite these physical barriers we show that somatically acquired mitochondrial-nuclear genome fusion sequences are present in cancer cells. Most occur in conjunction with intranuclear genomic rearrangements and the features of the fusion fragments indicate that non-homologous end joining and/or replication-dependent DNA double strand break repair are the dominant mechanism involved. This study includes 12 pairs of whole-genome sequences (tumour and paired-normal), which present somatic mitochondrial DNA integrations in tumour genomes. Reference: Young Seok Ju et al., Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells, Genome Research (2015).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-04-20T09:24:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001235","title":"Associations between APOE status and cognitive ability across the lifecourse","description":"The association between APOE genotype and cognitive function suggests a positive role for the e2 allele and a negative role for the e4 allele. Both alleles have relatively low frequencies in the general population, hence meta-analyses have been based on many small, heterogeneous studies. Here we report the APOE-cognition associations in the largest single analysis to date. APOE status and cognitive ability were measured in 18,337 participants from the Generation Scotland study between 2006 and 2011. The age range was 18-94 years with a mean of 47 (SD 15). Four cognitive domains were assessed: verbal declarative memory (paragraph recall), processing speed (digit symbol substitution), verbal fluency (phonemic verbal fluency), and vocabulary (Mill Hill synonyms). Linear regression was used to assess the associations between APOE genetic status and cognition. Possession of the e4 allele was associated with lower scores on the measures of memory and processing speed in subjects aged &gt;60. Across all age ranges, the e4 allele was linked to better verbal fluency scores. In younger subjects (≤60 years) the e4 allele was linked to higher vocabulary scores. There were no associations between the e2 allele and cognitive ability. As seen in previous meta-analyses, the APOE e4 allele is linked to poorer cognitive performance in the domains of memory and processing speed. By contrast, positive associations were seen between the e4 allele and measures of verbal fluency and vocabulary. All associations were relatively small and, in many cases, nominally significant despite the very large sample size.","abstract":"The association between APOE genotype and cognitive function suggests a positive role for the e2 allele and a negative role for the e4 allele. Both alleles have relatively low frequencies in the general population, hence meta-analyses have been based on many small, heterogeneous studies. Here we report the APOE-cognition associations in the largest single analysis to date. APOE status and cognitive ability were measured in 18,337 participants from the Generation Scotland study between 2006 and 2011. The age range was 18-94 years with a mean of 47 (SD 15). Four cognitive domains were assessed: verbal declarative memory (paragraph recall), processing speed (digit symbol substitution), verbal fluency (phonemic verbal fluency), and vocabulary (Mill Hill synonyms). Linear regression was used to assess the associations between APOE genetic status and cognition. Possession of the e4 allele was associated with lower scores on the measures of memory and processing speed in subjects aged &gt;60. Across all age ranges, the e4 allele was linked to better verbal fluency scores. In younger subjects (≤60 years) the e4 allele was linked to higher vocabulary scores. There were no associations between the e2 allele and cognitive ability. As seen in previous meta-analyses, the APOE e4 allele is linked to poorer cognitive performance in the domains of memory and processing speed. By contrast, positive associations were seen between the e4 allele and measures of verbal fluency and vocabulary. All associations were relatively small and, in many cases, nominally significant despite the very large sample size.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-04-21T09:58:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001236","title":"Comprehensive Transcriptional Analysis of Early Stage Urothelial Carcinoma using whole transcriptome sequencing","description":"The expression profile and sequence variants of 476 early stage urothelial carcinoma were studied using whole transcriptome sequencing. RNA-Seq libraries were prepared by Ribo-Zero treatment of total-RNA followed by library preparation using ScriptSeq (both Epicentre/Illumina). RNA-Seq libraries were paired-end sequenced (2x 101 bp) on Illumina HiSeq 2000 and the resulting fastq files were processed using tools from the Genome Analysis Toolkit (GATK and from the Tuxedo suite. \nAccess to the sequence data (mapped and un-mapped bam and vcf files), containing person identifying information, needs signature on a controlled access form, and can be accessed at The European Genome-phenome Archive (EGA) following request. An expression matrice of FPKM values are available without restriction at ArrayExpress (E-MTAB-4321).","abstract":"The expression profile and sequence variants of 476 early stage urothelial carcinoma were studied using whole transcriptome sequencing. RNA-Seq libraries were prepared by Ribo-Zero treatment of total-RNA followed by library preparation using ScriptSeq (both Epicentre/Illumina). RNA-Seq libraries were paired-end sequenced (2x 101 bp) on Illumina HiSeq 2000 and the resulting fastq files were processed using tools from the Genome Analysis Toolkit (GATK and from the Tuxedo suite. \nAccess to the sequence data (mapped and un-mapped bam and vcf files), containing person identifying information, needs signature on a controlled access form, and can be accessed at The European Genome-phenome Archive (EGA) following request. An expression matrice of FPKM values are available without restriction at ArrayExpress (E-MTAB-4321).","study_type":"Other","pubmed_ids":[27321955],"external_links":null,"is_released":true,"released_date":"2015-04-21T12:52:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001237","title":"SNP genotyping of multiplex autoimmune Addison's families from the UK and Norway","description":"Multiplex AAD families from the UK and Norway, genotyped on the Affymetrix SNP 6 array","abstract":"Multiplex AAD families from the UK and Norway, genotyped on the Affymetrix SNP 6 array","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-04-23T09:34:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001238","title":"Targeted_replication_of_LVOTO_genes","description":"Non-syndromic cases of congenital heart defects (CHD) exhibit variable modes of inheritance (Mendelian and non-Mendelian). Several studies have identified strong candidates in humans by taking a candidate gene approach as well as by using whole exome next generation sequencing (NGS). So far these studies could only explain a minor fraction of the observed phenotype in humans, most of them in syndromic cases and no single study has focused on the subset of cases with left ventricular outflow tract obstruction (LVOTO). To discover novel disease-causing genes a large cohort of patients with LVOTO, approximately 100 cases, 25 families and 100 trios have been exome sequenced. This study based on NGS sequencing data yielded several known and novel compelling candidate genes, such as MYH6, NR2F2 and MYH11, but also novel ones, such as ITGB4. To evaluate the significance of our findings in a replication cohort we assembled another 1614 cases with an LVOTO phenotype from our collaborators in Toronto, Berlin and Amsterdam. Targeted resequencing in this additional cohort will help to find additional cases with mutations in the identified candidate genes to strengthen genotype-phenotype association. We will use control data from the INTERVAL project for case/control analyses The pulldowns will be performed as 24-plex ISC with 192 or greater indexes, and the sequencing will be performed with 192 samples per lane, requiring 9 lanes of sequencing.","abstract":"Whole exome sequencing discovered several novel and known candidate genes associated human left ventricular outflow tract obstruction (LVOTO). To recapitulate these findings in an independent cohort of cases with LVOTO we used targeted resequencing of the of the previously identified genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-04-23T16:02:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001239","title":"Somatic_Variation_in_Humans_Adrenal_Gland","description":"This study is interested in lineage tracing of the adrenal gland. It will aid our understanding of phylogenetic relationships and contrasting mutational signatures between multiple functional and non-functional adrenal tumours and geographically sampled adrenal tissue.","abstract":"This study is interested in lineage tracing of the adrenal gland. It will aid our understanding of phylogenetic relationships and contrasting mutational signatures between multiple functional and non-functional adrenal tumours and geographically sampled adrenal tissue.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001240","title":"Exploring the role of mtDNA variation in Multiple Sclerosis in a large cohort of discordant monozygotic twins","description":"Several lines of evidence indicate that mitochondrial DNA (mtDNA) variants might predispose to multiple sclerosis (MS). We examined this in 49 monozygotic (MZ) twin pairs clinically discordant for MS at study entry. Since the nuclear DNA of MZ twins is identical, our study provides a unique setting to functionally associate unique mtDNA variants and skewed heteroplasmy with MS development. In order to identify mtDNA variants in the twin cohort, we deeply sequenced the mitochondrial genome in blood of all 49 MZ twin pairs using next generation sequencing (Illumina, HiSeq or MiSeq) with an average coverage depth of ~25,000 sequences per base. Heteroplasmic variants were validated using targeted deep sequencing (TDS) (Illumina, MiSeq) in DNA isolated from blood and buccal swabs. In addition, whole blood was also available of 5 additional MS-affected or healthy siblings and 1 dizygotic twin pair discordant for MS, comprising in total 6 non-identical sib pairs. Moreover, all cases were screened for pathogenic mtDNA polymerase gamma (POLG) mutations. The data provides valuable insights in the possible involvement of mtDNA variants in the pathogenesis of MS, and gives information on the segregation of heteroplasmic variants within MZ twins and non-identical siblings and across different tissues.","abstract":"Several lines of evidence indicate that mitochondrial DNA (mtDNA) variants might predispose to multiple sclerosis (MS). We examined this in 49 monozygotic (MZ) twin pairs clinically discordant for MS at study entry. Since the nuclear DNA of MZ twins is identical, our study provides a unique setting to functionally associate unique mtDNA variants and skewed heteroplasmy with MS development. In order to identify mtDNA variants in the twin cohort, we deeply sequenced the mitochondrial genome in blood of all 49 MZ twin pairs using next generation sequencing (Illumina, HiSeq or MiSeq) with an average coverage depth of ~25,000 sequences per base. Heteroplasmic variants were validated using targeted deep sequencing (TDS) (Illumina, MiSeq) in DNA isolated from blood and buccal swabs. In addition, whole blood was also available of 5 additional MS-affected or healthy siblings and 1 dizygotic twin pair discordant for MS, comprising in total 6 non-identical sib pairs. Moreover, all cases were screened for pathogenic mtDNA polymerase gamma (POLG) mutations. The data provides valuable insights in the possible involvement of mtDNA variants in the pathogenesis of MS, and gives information on the segregation of heteroplasmic variants within MZ twins and non-identical siblings and across different tissues.","study_type":"Metagenomics","pubmed_ids":[27119776],"external_links":null,"is_released":true,"released_date":"2015-04-26T15:20:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001241","title":"Genomics_in_Leukemia_Diagnosis__GILD_","description":"This study is meant to gain further knowledge in haematological cancers. Patients samples (mainly DNAs or PCR products) from haematolocical cancer patients will be sequenced for common mutated genes (as available from the publications so far available), and the outputs will be correlated to their diagnosis and/or prognosis.  More than 200 patients will be investigated. Some genes will be chosen for validation studies. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Advances in genomics have led to the identification of a number of recurrently mutated genes in haematological malignancies. Many of these influence prognosis and response to therapy.The detailed analysis of haematological cancer samples can greatly facilitate patient management and this study will test a carefully designed gene capture panel that will enable the simultaneous identification of recurrently mutated genes and also derive genome-wide copy number information from haematological malignancies.The genes were chosen to represent the majority of types of haematological cancers.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001242","title":"The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer","description":"Reactivation of telomerase reverse transcriptase (TERT) expression enables cells to overcome replicative senescence and escape apoptosis, fundamental steps in the initiation of human cancer.  Multiple cancer types, including up to 83% of glioblastomas (GBM), harbor highly recurrent TERT promoter mutations of unknown function but specific to two nucleotide positions. We identify the functional consequence of these mutations in GBM to be recruitment of the multimeric GABP transcription factor specifically to the mutant promoter. Allelic recruitment of GABP is consistently observed across four cancer types, highlighting a shared mechanism underlying TERT reactivation. Tandem flanking native ETS motifs critically cooperate with these mutations to activate TERT, likely by facilitating GABP heterotetramer binding. GABP thus directly links TERT promoter mutations to aberrant expression in multiple cancers.","abstract":"Reactivation of telomerase reverse transcriptase (TERT) expression enables cells to overcome replicative senescence and escape apoptosis, fundamental steps in the initiation of human cancer.  Multiple cancer types, including up to 83% of glioblastomas (GBM), harbor highly recurrent TERT promoter mutations of unknown function but specific to two nucleotide positions. We identify the functional consequence of these mutations in GBM to be recruitment of the multimeric GABP transcription factor specifically to the mutant promoter. Allelic recruitment of GABP is consistently observed across four cancer types, highlighting a shared mechanism underlying TERT reactivation. Tandem flanking native ETS motifs critically cooperate with these mutations to activate TERT, likely by facilitating GABP heterotetramer binding. GABP thus directly links TERT promoter mutations to aberrant expression in multiple cancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-04-30T05:49:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001243","title":"Dissecting genome aberration patterns in tumors","description":"We have developed a computational approach to analyse allele-specific copy number profiles from tumor DNA obtained with SNP arrays or by high-throughput sequencing. The proposed method, CARMA (Copy Aberration Regional Mapping Analysis) recognizes eight distinct patterns of genomic aberrations in tumors. Each pattern represents a particular mode of variation in individual copy number profiles, and together these patterns constitute a compact, biologically relevant representation of the genomic architecture in a tumor.","abstract":"We have developed a computational approach to analyse allele-specific copy number profiles from tumor DNA obtained with SNP arrays or by high-throughput sequencing. The proposed method, CARMA (Copy Aberration Regional Mapping Analysis) recognizes eight distinct patterns of genomic aberrations in tumors. Each pattern represents a particular mode of variation in individual copy number profiles, and together these patterns constitute a compact, biologically relevant representation of the genomic architecture in a tumor.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001244","title":"Intra-tumor heterogeneity and clonal evolution patterns towards platinum-resistant high-grade serous ovarian cancer","description":"Although many high-grade serous ovarian carcinoma (HGSOC) patients are initially sensitive to the standard-of-care platinum-based therapy, intra-tumor heterogeneity may fuel selection towards platinum-resistant clones over subsequent lines of therapy. We performed whole-exome coupled to ultra-deep re-sequencing and copy number alteration (CNA) profiling on 31 matched diagnosis and relapse tumors from HGSOC patients treated with platinum. Genetic heterogeneity within tumor pairs varied extremely, with some recurrent tumors being identical and others completely different from the primary tumor. All primary tumors showed evidence of homologous recombination (HR)-deficiency, but none of them carried reactivating mutations in the HR pathway at relapse, also not when becoming resistant to subsequent lines of platinum. We did also not identify other mutations, CNAs or pathways that were enriched in platinum-resistant clones. However, a platinum score consisting of 13 CNAs correlated significantly with platinum-free interval (PFI) after first-line therapy in multiple cohorts of &gt;450 primary HGSOCs. A relative increase of this score in the relapsed tumor correlated with a change in PFI during subsequent therapy. Clonal evolution under platinum therapy contributes to genetic heterogeneity within tumor pairs, implicating that genetic tests linked to targeted treatment options for recurrent HGSOC need to be performed on biopsies collected at relapse. Platinum resistance of an initially platinum-sensitive HR-deficient HGSOC at relapse is not caused by reactivation of the HR pathway, suggesting that these tumors are still responsive to PARP inhibitors, instead, several chromosomal aberrations contribute to a score predictive of disease outcome under platinum therapy, both in first and subsequent lines of platinum therapy.","abstract":"Although many high-grade serous ovarian carcinoma (HGSOC) patients are initially sensitive to the standard-of-care platinum-based therapy, intra-tumor heterogeneity may fuel selection towards platinum-resistant clones over subsequent lines of therapy. We performed whole-exome coupled to ultra-deep re-sequencing and copy number alteration (CNA) profiling on 31 matched diagnosis and relapse tumors from HGSOC patients treated with platinum. Genetic heterogeneity within tumor pairs varied extremely, with some recurrent tumors being identical and others completely different from the primary tumor. All primary tumors showed evidence of homologous recombination (HR)-deficiency, but none of them carried reactivating mutations in the HR pathway at relapse, also not when becoming resistant to subsequent lines of platinum. We did also not identify other mutations, CNAs or pathways that were enriched in platinum-resistant clones. However, a platinum score consisting of 13 CNAs correlated significantly with platinum-free interval (PFI) after first-line therapy in multiple cohorts of &gt;450 primary HGSOCs. A relative increase of this score in the relapsed tumor correlated with a change in PFI during subsequent therapy. Clonal evolution under platinum therapy contributes to genetic heterogeneity within tumor pairs, implicating that genetic tests linked to targeted treatment options for recurrent HGSOC need to be performed on biopsies collected at relapse. Platinum resistance of an initially platinum-sensitive HR-deficient HGSOC at relapse is not caused by reactivation of the HR pathway, suggesting that these tumors are still responsive to PARP inhibitors, instead, several chromosomal aberrations contribute to a score predictive of disease outcome under platinum therapy, both in first and subsequent lines of platinum therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-04T15:39:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001245","title":"Genomic Epidemiology of Complex Diseases in Population-based Brazilian Cohorts","description":"The EPIGEN-Brasil Initiative is so far the largest Latin American initiative in population genomics and genetic epidemiology. Its main goal is to study the association between genetic variants found in the Brazilian population and complex diseases, taking into account one of the most important characteristics of this population: its admixture. Population genetic include genomewide genotyping of 6487 individuals and high-resolution whole genome sequencing from 30 individuals from three population-based Brazilian cohorts: Salvador, Bambuí and Pelotas.  More information about the population-based cohorts are available on: For the 1982 Pelotas birth cohort study in Victora and Barros 2006 (PMID 16373375); For the Bambui cohort study of aging in LIma-Costa MF et al. (2011) (PMID 20805109); For the Salvador-Scaala study in Barreto et al. (2006) (PMID 16796729)","abstract":"The EPIGEN-Brasil Initiative is so far the largest Latin American initiative in population genomics and genetic epidemiology. Its main goal is to study the association between genetic variants found in the Brazilian population and complex diseases, taking into account one of the most important characteristics of this population: its admixture. Population genetic include genomewide genotyping of 6487 individuals and high-resolution whole genome sequencing from 30 individuals from three population-based Brazilian cohorts: Salvador, Bambuí and Pelotas.  More information about the population-based cohorts are available on: For the 1982 Pelotas birth cohort study in Victora and Barros 2006 (PMID 16373375); For the Bambui cohort study of aging in LIma-Costa MF et al. (2011) (PMID 20805109); For the Salvador-Scaala study in Barreto et al. (2006) (PMID 16796729)","study_type":"Other","pubmed_ids":[16373375,16796729,20805109],"external_links":null,"is_released":true,"released_date":"2015-05-04T21:05:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001246","title":"Biological indicators of resilience","description":"Individuals who have been exposed to acute or cumulative physical or mental traumas (e.g., body injury, pain, combat operations, terrorist attacks, bereavement, disagreement in significant relationships, financial and legal problems, dismissal from work, severe illness, and loss of a highly valued object) are at higher risk of developing anxiety, post-traumatic stress, major depressive or other psychiatric disorders with symptoms of chronic emotional distress and negative intrusive thoughts (fear of recurrence, magnification, rumination, and helplessness) and long-term disability in follow-up. However, not everyone develops negative symptoms after exposure to traumatic events, and individuals differ in the severity of symptoms and disability outcomes.  Researchers consider that such phenomenon as individual resilience or tolerance to a range of adverse events should explain these outcomes. Most researchers see no or only little difference in the concepts of ‘resilience’ and ‘adaptation’. However, these mechanisms could be related to fundamentally different biological processes, regulating flexibility and stability. Physiological resilience and adaptation work as two attractors for different physiological regulations in terms of the Chaos Theory. It extends our understanding of how disorders may be prevented in ways beyond adaptation. Resilience mechanisms are suggested to help (i) to protect an organism from transfer of adaptive reactivity to over-adaptation, which leads to ‘destroying’ one’s structural and functional organization as the main part of the aging process, (ii) to balance biological, psychological and social arousing effects in interaction with adaptation mechanisms for development of healthy trade-offs between tolerance and sensitivity to events, as a process of phenotyping a genetic range of predispositions in specific environments.","abstract":"Individuals who have been exposed to acute or cumulative physical or mental traumas (e.g., body injury, pain, combat operations, terrorist attacks, bereavement, disagreement in significant relationships, financial and legal problems, dismissal from work, severe illness, and loss of a highly valued object) are at higher risk of developing anxiety, post-traumatic stress, major depressive or other psychiatric disorders with symptoms of chronic emotional distress and negative intrusive thoughts (fear of recurrence, magnification, rumination, and helplessness) and long-term disability in follow-up. However, not everyone develops negative symptoms after exposure to traumatic events, and individuals differ in the severity of symptoms and disability outcomes.  Researchers consider that such phenomenon as individual resilience or tolerance to a range of adverse events should explain these outcomes. Most researchers see no or only little difference in the concepts of ‘resilience’ and ‘adaptation’. However, these mechanisms could be related to fundamentally different biological processes, regulating flexibility and stability. Physiological resilience and adaptation work as two attractors for different physiological regulations in terms of the Chaos Theory. It extends our understanding of how disorders may be prevented in ways beyond adaptation. Resilience mechanisms are suggested to help (i) to protect an organism from transfer of adaptive reactivity to over-adaptation, which leads to ‘destroying’ one’s structural and functional organization as the main part of the aging process, (ii) to balance biological, psychological and social arousing effects in interaction with adaptation mechanisms for development of healthy trade-offs between tolerance and sensitivity to events, as a process of phenotyping a genetic range of predispositions in specific environments.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001247","title":"Papuan Genomes: whole genome sequencing","description":"The genomes of 25 individuals from Papua New Guinea was sequenced to high depth (30x) to address population genetic questions relating to the spread of humans outside of Africa and the peopling of Sahul (the continent of Greater Australia). The study design of this project was to sequence small numbers of genomes from several geographically distinct Papuan groups, focusing on the highland regions that are thought to have been more isolated, to enable comparisons between populations within Papua New Guinea and with Australian Aboriginal populations. Data from this project feed directly into on-going projects on the genetic history of Australia and also serve as a first look at the population genomics of the Papuan highlands.","abstract":"The genomes of 25 individuals from Papua New Guinea was sequenced to high depth (30x) to address population genetic questions relating to the spread of humans outside of Africa and the peopling of Sahul (the continent of Greater Australia). The study design of this project was to sequence small numbers of genomes from several geographically distinct Papuan groups, focusing on the highland regions that are thought to have been more isolated, to enable comparisons between populations within Papua New Guinea and with Australian Aboriginal populations. Data from this project feed directly into on-going projects on the genetic history of Australia and also serve as a first look at the population genomics of the Papuan highlands.","study_type":"Other","pubmed_ids":[27654914],"external_links":null,"is_released":true,"released_date":"2015-05-07T09:58:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001248","title":"EGA Test Study","description":"Test","abstract":"Test","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001249","title":"EGA Test Study","description":"Test","abstract":"Test","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001250","title":"Exome Sequencing in Moebius Syndrome","description":"Möbius syndrome (MBS; MIM 157900) is a neurological disorder that is characterized by paralysis of the facial nerves and variable other congenital anomalies. The etiology of this syndrome has been an enigma since the initial description in 1880 by von Graaefe and in 1888 by Möbius, and it has been debated for decades whether MBS has a genetic or a non-genetic etiology. Here, we reveal various de novo mutations affecting two genes, PLXND1 and REV3L. The finding that de novo mutations can cause Möbius syndrome will have considerable impact on further research, as well as in diagnostics. PLXND1 and REV3L represent totally unrelated pathways involved in hindbrain development: neural migration and DNA translesion synthesis, essential for the replication of endogenously damaged DNA. However, analysis of Plxnd1 and Rev3l-mutant mice revealed that both genetic defects converge at the facial branchiomotor nucleus, affecting either motoneuron migration or proliferation.","abstract":"Möbius syndrome (MBS; MIM 157900) is a neurological disorder that is characterized by paralysis of the facial nerves and variable other congenital anomalies. The etiology of this syndrome has been an enigma since the initial description in 1880 by von Graaefe and in 1888 by Möbius, and it has been debated for decades whether MBS has a genetic or a non-genetic etiology. Here, we reveal various de novo mutations affecting two genes, PLXND1 and REV3L. The finding that de novo mutations can cause Möbius syndrome will have considerable impact on further research, as well as in diagnostics. PLXND1 and REV3L represent totally unrelated pathways involved in hindbrain development: neural migration and DNA translesion synthesis, essential for the replication of endogenously damaged DNA. However, analysis of Plxnd1 and Rev3l-mutant mice revealed that both genetic defects converge at the facial branchiomotor nucleus, affecting either motoneuron migration or proliferation.","study_type":"Other","pubmed_ids":[26068067],"external_links":null,"is_released":true,"released_date":"2015-05-08T15:44:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001251","title":"Leucocyte eQTLs in autoimmune disease and health","description":"Peripheral blood was taken from healthy controls and patients with active autoimmune disease. CD4 T cells, CD8 T cells, monocytes, neutrophils, and B cells were separated using magnetic-activated cell sorting. RNA and genomic DNA was extracted from cell lysates using Qiagen Allprep kits. Genotyping of healthy controls and patients with inflammatory bowel disease was performed using the Illumina Human OmniExpress12v1.0 BeadChip at the Wellcome Trust Sanger Institute. 200 ng RNA was processed for hybridization onto Affymetrix Human Gene ST 1.1 microarrays. Gene expression and genotyping data was used to perform eQTL mapping.","abstract":"Peripheral blood was taken from healthy controls and patients with active autoimmune disease. CD4 T cells, CD8 T cells, monocytes, neutrophils, and B cells were separated using magnetic-activated cell sorting. RNA and genomic DNA was extracted from cell lysates using Qiagen Allprep kits. Genotyping of healthy controls and patients with inflammatory bowel disease was performed using the Illumina Human OmniExpress12v1.0 BeadChip at the Wellcome Trust Sanger Institute. 200 ng RNA was processed for hybridization onto Affymetrix Human Gene ST 1.1 microarrays. Gene expression and genotyping data was used to perform eQTL mapping.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-09T17:38:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001252","title":"Engineering of a promoterless anti-viral RNAi hairpin into an endogenous miRNA locus","description":"Short hairpin RNA (shRNA) expression strategies that allow safe and persistent target mRNA knockdown are key to the success of many in vitro or in vivo RNAi applications. Here, we propose a novel solution which is expression of a promoterless miRNA-adapted shRNA (shmiRNA) from an engineered genomic miRNA locus. For proof-of-concept, we genetically “vaccinated” liver cells against a human pathogen, by using TALEns or CRISPR to integrate an anti-hepatitis C virus (HCV) shmiRNA into the liver-specific miR-122/hcr gene. Reporter assays and qRT-PCR confirmed anti-HCV shmiRNA expression as well as miR-122 integrity and functionality. Specificity and safety of shmiRNA integration were validated via PCR, cDNA and miRNA profiling, and whole genome sequencing. A subgenomic HCV replicon and a full-length reporter virus, but not a Dengue virus control, were significantly impaired in the modified cells. Our original combination of DNA engineering and RNAi expression technologies should benefit numerous applications, from basic miRNA research, to human cell and gene therapy.","abstract":"Short hairpin RNA (shRNA) expression strategies that allow safe and persistent target mRNA knockdown are key to the success of many in vitro or in vivo RNAi applications. Here, we propose a novel solution which is expression of a promoterless miRNA-adapted shRNA (shmiRNA) from an engineered genomic miRNA locus. For proof-of-concept, we genetically “vaccinated” liver cells against a human pathogen, by using TALEns or CRISPR to integrate an anti-hepatitis C virus (HCV) shmiRNA into the liver-specific miR-122/hcr gene. Reporter assays and qRT-PCR confirmed anti-HCV shmiRNA expression as well as miR-122 integrity and functionality. Specificity and safety of shmiRNA integration were validated via PCR, cDNA and miRNA profiling, and whole genome sequencing. A subgenomic HCV replicon and a full-length reporter virus, but not a Dengue virus control, were significantly impaired in the modified cells. Our original combination of DNA engineering and RNAi expression technologies should benefit numerous applications, from basic miRNA research, to human cell and gene therapy.","study_type":"Other","pubmed_ids":[27614072],"external_links":null,"is_released":true,"released_date":"2015-05-11T14:22:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001253","title":"Microinjection_of_hIPSC_derived_intestinal_organoids_with_Salmonella_Typhimurium","description":"To generate an RNA-Seq dataset for organoids apically stimulated with Salmonella Typhimurium.These data are part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"To use intestinal organoids derived from hIPSCs to characterise the interactions between enteric pathogens and host epithelial cells.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-13T10:24:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001254","title":"Tracking the genomic evolution of esophageal adenocarcinoma through neoadjuvant chemotherapy","description":"Esophageal adenocarcinomas (EACs) are associated with dismal prognosis. Deciphering the evolutionary histories of this disease may shed light on therapeutically tractable targets and reveal changing mutational processes during the disease course and following neoadjuvant chemotherapy (NAC). We exome sequenced 40 tumor regions from 8 patients with operable EACs both before and after platinum-containing NAC. This revealed the evolutionary genomic landscape of EACs with the presence of heterogeneous driver mutations, parallel evolution, early genome doubling events and an association between high intratumor heterogeneity and poor response to NAC. Multi-region sequencing demonstrated a significant reduction in T&gt;G mutations within a CTT context when comparing early and late mutational processes and the presence of a platinum signature with enrichment of C&gt;A mutations within a CpC context following NAC. EACs are characterized by the presence of amplifications containing targetable oncogenes present before and after chemotherapy that may provide a rationale for future therapeutic approaches.","abstract":"Esophageal adenocarcinomas (EACs) are associated with dismal prognosis. Deciphering the evolutionary histories of this disease may shed light on therapeutically tractable targets and reveal changing mutational processes during the disease course and following neoadjuvant chemotherapy (NAC). We exome sequenced 40 tumor regions from 8 patients with operable EACs both before and after platinum-containing NAC. This revealed the evolutionary genomic landscape of EACs with the presence of heterogeneous driver mutations, parallel evolution, early genome doubling events and an association between high intratumor heterogeneity and poor response to NAC. Multi-region sequencing demonstrated a significant reduction in T&gt;G mutations within a CTT context when comparing early and late mutational processes and the presence of a platinum signature with enrichment of C&gt;A mutations within a CpC context following NAC. EACs are characterized by the presence of amplifications containing targetable oncogenes present before and after chemotherapy that may provide a rationale for future therapeutic approaches.","study_type":"Other","pubmed_ids":[26003801],"external_links":null,"is_released":true,"released_date":"2015-05-13T15:43:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001255","title":"DNA methylation and somatic mutations converge on cell cycle and define similar evolutionary histories in brain tumors","description":"The evolutionary history of tumor cell populations can be reconstructed from patterns of genetic alterations. In contrast to the stability of genetic events, epigenetic states are reversible and sensitive to the microenvironment, prompting the question whether epigenetics can be similarly used to discover tumor phylogeny. We examined the spatial and temporal dynamics of DNA methylation in a cohort of low-grade gliomas and their patient-matched recurrences. Genes upregulated through promoter hypomethylation during malignant progression to high-grade glioblastoma were enriched in cell cycle function, evolving in parallel with genetic alterations that deregulate the G1/S cell cycle checkpoint. Moreover, phyloepigenetic relationships robustly recapitulated phylogenetic patterns inferred from somatic mutations. These findings highlight widespread co-dependency of genetic and epigenetic events throughout brain tumor evolution.","abstract":"The evolutionary history of tumor cell populations can be reconstructed from patterns of genetic alterations. In contrast to the stability of genetic events, epigenetic states are reversible and sensitive to the microenvironment, prompting the question whether epigenetics can be similarly used to discover tumor phylogeny. We examined the spatial and temporal dynamics of DNA methylation in a cohort of low-grade gliomas and their patient-matched recurrences. Genes upregulated through promoter hypomethylation during malignant progression to high-grade glioblastoma were enriched in cell cycle function, evolving in parallel with genetic alterations that deregulate the G1/S cell cycle checkpoint. Moreover, phyloepigenetic relationships robustly recapitulated phylogenetic patterns inferred from somatic mutations. These findings highlight widespread co-dependency of genetic and epigenetic events throughout brain tumor evolution.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-13T19:27:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001256","title":"Genetic_screening__of_GPI_anchor_protein_synthesis__","description":"This study will analyse the guide sequence which were used for making mutations in the Cas9-expressing cells. We used GeCKO v2 library which were released by Feng Zhang, 2014. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"CRISPR/Cas9 system has been applied for generating mutations in the whole genome. For identifying genes involved in the GPI biosynthesis pathway, mutated cells by CRISPR/Cas9 system were screened against proaerolysin. Sequences of guide RNA which generate loss of gene function in GPI biosynthesis will be analysed by illumina sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-14T09:00:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001257","title":"Clinical Implications of Genomic Alterations in the Tumor and Circulation of Pancreatic Cancer Patients","description":"Pancreatic adenocarcinoma has the worst mortality of any solid cancer.  To evaluate the clinical implications of genomic alterations in this tumor type, we performed whole-exome analyses of 24 tumors, targeted genomic analyses of 77 tumors, and used non-invasive approaches to examine tumor-specific mutations in the circulation of these patients.  These analyses reveal somatic mutations in chromatin regulating genes MLL, MLL2, MLL3, and ARID1A in 20% of patients that were associated with improved survival.  We observe alterations in genes with potential clinical utility in over a third of cases.  Liquid biopsy analyses demonstrate that 43% of patients with localized disease have detectable circulating tumor DNA (ctDNA) at diagnosis.  Detection of ctDNA after resection predicts clinical relapse and poor outcome, and recurrence by ctDNA is detected 6.5 months earlier than with CT imaging.  These observations provide genetic predictors of outcome in pancreatic cancer and have implications for new avenues of therapeutic intervention.","abstract":"Pancreatic adenocarcinoma has the worst mortality of any solid cancer.  To evaluate the clinical implications of genomic alterations in this tumor type, we performed whole-exome analyses of 24 tumors, targeted genomic analyses of 77 tumors, and used non-invasive approaches to examine tumor-specific mutations in the circulation of these patients.  These analyses reveal somatic mutations in chromatin regulating genes MLL, MLL2, MLL3, and ARID1A in 20% of patients that were associated with improved survival.  We observe alterations in genes with potential clinical utility in over a third of cases.  Liquid biopsy analyses demonstrate that 43% of patients with localized disease have detectable circulating tumor DNA (ctDNA) at diagnosis.  Detection of ctDNA after resection predicts clinical relapse and poor outcome, and recurrence by ctDNA is detected 6.5 months earlier than with CT imaging.  These observations provide genetic predictors of outcome in pancreatic cancer and have implications for new avenues of therapeutic intervention.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-15T14:56:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001258","title":"Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis","description":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","abstract":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-18T17:34:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001259","title":"WES sequencing of 100 human esophageal carcinoma cases","description":"WES sequencing of 100 human esophageal carcinoma cases","abstract":"WES sequencing of 100 human esophageal carcinoma cases","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001260","title":"Understand_Paratyphoid_Disease___host_responses_to_human_challenge_with_S__Paratyphi_A","description":"This project aims to evaluate the transcriptional response to disease measured in whole blood of participants who developed enteric fever after challenge and, importantly, those who were challenged but stayed well throughout the challenge period. This data will provide unique coverage of the transcriptome and will yield invaluable insight after integration with a wealth of clinical data collected during this trial.      This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This project aims to evaluate the transcriptional response to disease measured in whole blood of participants who developed enteric fever after challenge and, importantly, those who were challenged but stayed well throughout the challenge period","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-19T11:55:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001261","title":"Colorectal_Adenoma_Gene_Screen","description":"A pilot to establish the feasability of using a custom Agilent targeted pulldown of 110 genes implicated in colorectal tumourigensis to sequence for driver mutations in a set of 30 FFPE colorectal adenomas. If successful, we propose to sequence an additional 350 adenomas as part of a MRC research study in order to define the pattern of driver mutations across the spectrum of pathological subtypes including coventional adenomas, serrated adenomas and hyperplastic polyps","abstract":"A pilot to establish the feasability of using a custom Agilent targeted pulldown of 110 genes implicated in colorectal tumourigensis to sequence for driver mutations in a set of 30 FFPE colorectal adenomas. If successful, we propose to sequence an additional 350 adenomas as part of a MRC research study in order to define the pattern of driver mutations across the spectrum of pathological subtypes including coventional adenomas, serrated adenomas and hyperplastic polyps","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-19T14:28:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001262","title":"Deciphering the mutational landscape and the genome organization of LMS","description":"Leiomyosarcoma (LMS) are an uncommon group of malignant mesenchymal tumors composed of cells showing distinct smooth muscle differentiation. These tumors occur mainly in adults in any location of the body (soft-tissue, viscera or uterine). Soft-tissue LMS represent 10-15% of all soft-tissue sarcomas. The most frequent locations are the limbs followed by the retroperitoneum and uterine.","abstract":"Leiomyosarcoma (LMS) are an uncommon group of malignant mesenchymal tumors composed of cells showing distinct smooth muscle differentiation. These tumors occur mainly in adults in any location of the body (soft-tissue, viscera or uterine). Soft-tissue LMS represent 10-15% of all soft-tissue sarcomas. The most frequent locations are the limbs followed by the retroperitoneum and uterine.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-20T10:40:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001263","title":"Exome_Sequencing_of_Human_myeloid_malignancies","description":"This study involves exome sequencing of blood/bone marrow DNA from patients with myeloid malignancies. Blood DNA samples have been taken from patients at different timepoints of disease phenotype. We hope to elucidate mechanisms of clonal evolution in these patients.","abstract":"This study involves exome sequencing of blood/bone marrow DNA from patients with myeloid malignancies. Blood DNA samples have been taken from patients at different timepoints of disease phenotype. We hope to elucidate mechanisms of clonal evolution in these patients.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-20T13:39:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001264","title":"CMML Collection of WES, WGS, RNA-Seq and ERRBS data","description":"We first performed a comprehensive analysis of the genome of 66 chronic myelomonocytic leukemia cases using whole exome (N=49) or whole genome (N=17) sequencing for paired leukemic-control DNA. Then, we realized serial analysis of whole exome sequence in 17 cases, completed with serial RNA sequencing and DNA methylation analysis in 9 cases, including patients treated or not with hypomethylating agents.","abstract":"We first performed a comprehensive analysis of the genome of 66 chronic myelomonocytic leukemia cases using whole exome (N=49) or whole genome (N=17) sequencing for paired leukemic-control DNA. Then, we realized serial analysis of whole exome sequence in 17 cases, completed with serial RNA sequencing and DNA methylation analysis in 9 cases, including patients treated or not with hypomethylating agents.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-20T14:38:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001265","title":"cis-eQTL mapping of human pancreatic islets","description":"The intersection of genome-wide association analyses with physiological and functional data indicates that variants regulating islet gene transcription influence type 2 diabetes  predisposition and glucose homeostasis. However, the specific genes through which these regulatory variants act remain poorly characterized. In this study, we generated eQTL data from human islet samples to establish the extent to which this allowed us to identify candidate effector transcripts at GWAS loci for T2D and glycemic traits.","abstract":"The intersection of genome-wide association analyses with physiological and functional data indicates that variants regulating islet gene transcription influence type 2 diabetes  predisposition and glucose homeostasis. However, the specific genes through which these regulatory variants act remain poorly characterized. In this study, we generated eQTL data from human islet samples to establish the extent to which this allowed us to identify candidate effector transcripts at GWAS loci for T2D and glycemic traits.","study_type":"Metagenomics","pubmed_ids":[26624892],"external_links":null,"is_released":true,"released_date":"2015-05-21T13:12:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001266","title":"Preeclampsia InterPregGen Consortium: Large-scale GWAS meta-analysis of maternal preclampsia cases and controls from Europe and Central Asia. Plus extension of earlier European fetal preeclampsia GWAS meta-analysis (see EGAS00001001048) by adding Central Asian fetal preeclampsia cases and controls. Datasets provided under this study are GWAS meta-analysis summary statistics and individual level GWAS genotype data. Related InterPregGen Consortium data are also provided under studies EGAS00001000416 and EGAS00001000417 (whole genome sequence data for 100 unrelated Uzbeks and 100 unrelated Kazakhs) and EGAS00001001048 (European fetal preeclampsia GWAS summary statistics and genotype data","description":"Preeclampsia (PE) is a syndrome affecting pregnant mothers and fetus/babies characterised by hypertension and proteinuria, and is a leading cause of maternal and fetal death and of premature births worldwide. The InterPregGen Consortium was funded by a European Framework 7 (FP7) grant and grew out of the WTCCC3 GWAS comparing ~2000 UK PE mothers with ~6000 common UK controls. The EGAS00001001266 study includes two components the FP7 InterPregGen project:\n(a) GWAS case-control meta-analysis of maternal PE cases from Europe (UK, Iceland, Norway, Denmark, Finland) and Central Asia (Kazakhstan, Uzbekistan); (b) GWAS case-control meta-analysis of PE fetal (baby) cases from Europe (UK, Iceland, Norway, Denmark) and Central Asia (Kazakhstan, Uzbekistan)","abstract":"Preeclampsia (PE) is a syndrome affecting pregnant mothers and fetus/babies characterised by hypertension and proteinuria, and is a leading cause of maternal and fetal death and of premature births worldwide. The InterPregGen Consortium was funded by a European Framework 7 (FP7) grant and grew out of the WTCCC3 GWAS comparing ~2000 UK PE mothers with ~6000 common UK controls. The EGAS00001001266 study includes two components the FP7 InterPregGen project:\n(a) GWAS case-control meta-analysis of maternal PE cases from Europe (UK, Iceland, Norway, Denmark, Finland) and Central Asia (Kazakhstan, Uzbekistan); (b) GWAS case-control meta-analysis of PE fetal (baby) cases from Europe (UK, Iceland, Norway, Denmark) and Central Asia (Kazakhstan, Uzbekistan)","study_type":"Other","pubmed_ids":[33239696],"external_links":null,"is_released":true,"released_date":"2015-05-22T12:44:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001267","title":"RNAseq_and_proteomics_of_infected_macrophages_derived_from_first_KO_human_iPS_cell_line","description":"RNAseq and proteomics of infected macrophages derived from first KO human iPS cell lineThese data are part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"RNAseq and proteomics of infected macrophages derived from first KO human iPS cell line","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001268","title":"Whole exome sequencing of papillary thyroid carcinoma in the Chinese population","description":"Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here we submitted the sequencing results for PTC using 91 tumor-normal pairs through exome sequencing in the Chinese Han population.","abstract":"Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here we submitted the sequencing results for PTC using 91 tumor-normal pairs through exome sequencing in the Chinese Han population.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-25T02:12:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001269","title":"Colorectal cancer sequencing project of Cancer Institute of Zhejiang University (China)","description":"We performed whole genome sequencing for 10 pairs tumor samples and exome sequencing for 72 pairs tumor samples of colorectal cancer patients.","abstract":"We performed whole genome sequencing for 10 pairs tumor samples and exome sequencing for 72 pairs tumor samples of colorectal cancer patients.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-05-26T01:58:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001270","title":"Quality and quantity of miRNA in Janus SerumBank","description":"Background: The impacts of long-term storage and varying pre-analytical factors on the quality and quantity of DNA and microRNA (miRNA) from archived serum have not been fully assessed. Pre-analytical and analytical variations and degradation may introduce bias in representation of DNA and miRNA and may result in loss or corruption of quantitative data.  Methods: We have evaluated DNA and miRNA quantity, quality and variability in samples stored up to 40 years using one of the oldest serum collections, the Janus Serumbank, a biorepository dedicated to cancer research.  Results: miRNAs are present and stable in archived serum samples frozen at ‒25°C for at least 40 years. Longtime-storage did not reduce miRNA yields, however, varying pre-analytical conditions had a significant effect and should be taken into consideration during project design. 500µl serum yielded sufficient miRNA for qPCR and small RNA sequencing and on average 650 unique miRNAs were detected in samples from presumably healthy donors. 500µl serum yielded sufficient DNA for whole-genome sequencing and subsequent SNP calling, giving a uniform representation of the genomes.  Conclusions: DNA and miRNA are stable during long-term storage, making large prospectively collected serum repositories an invaluable source for miRNA and DNA biomarker discovery. Impact: Large-scale cancer biomarker studies with long follow-up times are possible utilizing biorepositories with archived serum and state-of-the-art technology.","abstract":"Background: The impacts of long-term storage and varying pre-analytical factors on the quality and quantity of DNA and microRNA (miRNA) from archived serum have not been fully assessed. Pre-analytical and analytical variations and degradation may introduce bias in representation of DNA and miRNA and may result in loss or corruption of quantitative data.  Methods: We have evaluated DNA and miRNA quantity, quality and variability in samples stored up to 40 years using one of the oldest serum collections, the Janus Serumbank, a biorepository dedicated to cancer research.  Results: miRNAs are present and stable in archived serum samples frozen at ‒25°C for at least 40 years. Longtime-storage did not reduce miRNA yields, however, varying pre-analytical conditions had a significant effect and should be taken into consideration during project design. 500µl serum yielded sufficient miRNA for qPCR and small RNA sequencing and on average 650 unique miRNAs were detected in samples from presumably healthy donors. 500µl serum yielded sufficient DNA for whole-genome sequencing and subsequent SNP calling, giving a uniform representation of the genomes.  Conclusions: DNA and miRNA are stable during long-term storage, making large prospectively collected serum repositories an invaluable source for miRNA and DNA biomarker discovery. Impact: Large-scale cancer biomarker studies with long follow-up times are possible utilizing biorepositories with archived serum and state-of-the-art technology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001271","title":"ChIP_seq_Tregs","description":"This project includes functional genomic data derived from regulatory T cells from 80 healthy individuals. This includes genotypes from illuminaCoreExome platform, RNA-seq, ChIP-seq and ATAC-seq data.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This project includes functional genomic data derived from regulatory T cells from 80 healthy individuals. This includes genotypes from illuminaCoreExome platform, RNA-seq, ChIP-seq and ATAC-seq data.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001272","title":"HipSci HumanExome BeadChip analysis-Rare_BBS","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bardet-Biedl syndrome.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bardet-Biedl syndrome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-04T11:22:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001273","title":"HipSci HumanExome BeadChip analysis - monogenic diabetes","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with monogenic diabetes.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with monogenic diabetes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-04T11:26:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001274","title":"HipSci Illumina 450K Methylation analysis-Rare_BBS","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium HumanMethylation450 BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bardet-Biedl syndrome.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium HumanMethylation450 BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bardet-Biedl syndrome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-04T11:29:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001275","title":"HipSci Illumina 450K Methylation analysis - monogenic diabetes","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium HumanMethylation450 BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with monogenic diabetes.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium HumanMethylation450 BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with monogenic diabetes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-04T11:31:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001276","title":"HipSci HumanHT 12v4 Expression BeadChip analysis-Rare_BBS","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bardet-Biedl syndrome.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bardet-Biedl syndrome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-04T11:33:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001277","title":"HipSci HumanHT 12v4 Expression BeadChip analysis - monogenic diabetes","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with monogenic diabetes.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with monogenic diabetes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-04T11:36:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001278","title":"Pilot_project_for_Chip_seq_on_regulatory_T_cells","description":"This project includes functional genomic data derived from regulatory T cells from healthyindividuals. This includes genotypes from IlluminaCore Exome platform, RNA-seq, ChIP-seqand ATAC-seq data.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This project includes functional genomic data derived from regulatory T cells from healthyindividuals. This includes genotypes from IlluminaCore Exome platform, RNA-seq, ChIP-seqand ATAC-seq data","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001279","title":"Novel Epigenetic Markers for Toxicity after Intraoperative and Conventional Radiotherapy for Breast Cancer","description":"Ionizing radiation is a common treatment option for cancer but its use is limited by the unpredictable and highly heterogeneous onset of late side effects, especially radiation-induced fibrosis. Clinically applicable biomarkers and effective treatments for radiation fibrosis are currently unavailable. In order to identify novel markers we ran a genome-wide DNA methylation screen in primary dermal fibroblasts obtained from breast cancer patients before intraoperative radiotherapy. Cells from patients developing fibrosis within a three-year follow up were compared to those without fibrosis (12 individuals per group). Illumina Infinium HumanMethylation450 BeadChip Technology was used.","abstract":"Ionizing radiation is a common treatment option for cancer but its use is limited by the unpredictable and highly heterogeneous onset of late side effects, especially radiation-induced fibrosis. Clinically applicable biomarkers and effective treatments for radiation fibrosis are currently unavailable. In order to identify novel markers we ran a genome-wide DNA methylation screen in primary dermal fibroblasts obtained from breast cancer patients before intraoperative radiotherapy. Cells from patients developing fibrosis within a three-year follow up were compared to those without fibrosis (12 individuals per group). Illumina Infinium HumanMethylation450 BeadChip Technology was used.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-06T11:40:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001280","title":"CTTV019__Development_of_cellular_intestinal_disease_models_for_target_validation","description":"The understanding of cellular processes in disease has been advanced by the study ofhuman disease tissue.  For the study of Crohn’s pathology a number of approaches havebeen utilised (Lee et al JCI 2011; Vossenkamper et al Gastro 2014). The two approachesmost widely employed are, firstly the study of intact punch biopsies and secondly, theisolation of cells from bowel resections. The current proposal seeks to establish both of thesemethods to enable the validation of a spectrum of potential targets, improve upon currentmodels and explore new model systems.This proposal (Project 3) is part of the CTTV disease focus where:Project 1 - Disease ontologies and informatics.Project 2 - Human genetics/GWAS of IBD.Project 3 - Cellular and tissue modelsa. Establish cellular disease models - iPS, punch biopsy, bowel resectionb. Establish blood derived primary cell systemsc. Establish intestinal organoid disease modeld. Establish a long-lived patient-derived tissue modele. Use systems a,b,c for target perturbation studies (eg. CRISPR, tool compounds) of highconfidence genes or gene variants identified from project 2 to understand their role in diseasebiologyf. Conduct metagenomics on disease and non-disease tissue biopsies, attempting to identifybacterial species with a role in the development of diseaseThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The understanding of cellular processes in disease has been advanced by the study ofhuman disease tissue.  For the study of Crohn’s pathology a number of approaches havebeen utilised (Lee et al JCI 2011; Vossenkamper et al Gastro 2014). The two approachesmost widely employed are, firstly the study of intact punch biopsies and secondly, theisolation of cells from bowel resections. The current proposal seeks to establish both of thesemethods to enable the validation of a spectrum of potential targets, improve upon currentmodels and explore new model systems.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001281","title":"PLCG1 R707Q mutation is counter selected under targeted therapy in a patient with a hepatic angiosarcoma","description":"PLCG1 R707Q mutation is counter selected under targeted therapy in a patient with a hepatic angiosarcoma","abstract":"PLCG1 R707Q mutation is counter selected under targeted therapy in a patient with a hepatic angiosarcoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-08T13:38:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001282","title":"CTTV019__Development_of_cellular_intestinal_disease_models_for_target_validation","description":"The understanding of cellular processes in disease has been advanced by the study ofhuman disease tissue.  For the study of Crohn’s pathology a number of approaches havebeen utilised (Lee et al JCI 2011; Vossenkamper et al Gastro 2014). The two approachesmost widely employed are, firstly the study of intact punch biopsies and secondly, theisolation of cells from bowel resections. The current proposal seeks to establish both of thesemethods to enable the validation of a spectrum of potential targets, improve upon currentmodels and explore new model systems.This proposal (Project 3) is part of the CTTV disease focus where:Project 1 - Disease ontologies and informatics.Project 2 - Human genetics/GWAS of IBD.Project 3 - Cellular and tissue modelsa. Establish cellular disease models - iPS, punch biopsy, bowel resectionb. Establish blood derived primary cell systemsc. Establish intestinal organoid disease modeld. Establish a long-lived patient-derived tissue modele. Use systems a,b,c for target perturbation studies (eg. CRISPR, tool compounds) of highconfidence genes or gene variants identified from project 2 to understand their role in diseasebiologyf. Conduct metagenomics on disease and non-disease tissue biopsies, attempting to identifybacterial species with a role in the development of diseaseThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The understanding of cellular processes in disease has been advanced by the study ofhuman disease tissue.  For the study of Crohn’s pathology a number of approaches havebeen utilised (Lee et al JCI 2011; Vossenkamper et al Gastro 2014). The two approachesmost widely employed are, firstly the study of intact punch biopsies and secondly, theisolation of cells from bowel resections. The current proposal seeks to establish both of thesemethods to enable the validation of a spectrum of potential targets, improve upon currentmodels and explore new model systems.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001283","title":"IL_10_signalling_and_macrophage_gene_expression","description":"Study to stimulate WT and IL-10RB mutant macrophages with LPS in presence or absence of recombinant IL-10 and compare their gene expression profiles by RNASeqThese data are part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Aim to understand how IL-10 inhibits LPSinduced inflammatory gene expression in macrophages","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-09T09:47:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001284","title":"Recurrent adeno-associated virus 2-related insertional mutagenesis in human hepatocellular carcinomas","description":"Hepatocellular carcinomas (HCC) are liver tumors related to various etiologies including alcohol intake, hepatitis B (HBV) or C (HCV) virus infection. Additional risk factors remain to be identified, particularly in patients who develop HCC without cirrhosis. We identified clonal integration of adeno-associated virus type 2 (AAV2) in 11 out of 193 HCC. These AAV2 integrations occurred within known cancer driver genes, namely, CCNA2 (Cyclin A2, 4 cases), TERT (Telomerase Reverse-Transcriptase, 1 case), CCNE1 (Cyclin E1, 3 cases), TNFSF10 (Tumor Necrosis Factor member 10, 2 cases) or KMT2B (Lysine (K)-Specific Methyltransferase 2B, 1 case) leading to over-expression of the target genes. Tumors with viral integration mainly developed in non-cirrhotic liver (9 out of 11 cases) and without known risk factors (6 out of 11) suggesting a pathogenic role of AAV2 in these patients. In conclusion, AAV2 is a DNA virus associated with oncogenic insertional mutagenesis in human HCC.","abstract":"Hepatocellular carcinomas (HCC) are liver tumors related to various etiologies including alcohol intake, hepatitis B (HBV) or C (HCV) virus infection. Additional risk factors remain to be identified, particularly in patients who develop HCC without cirrhosis. We identified clonal integration of adeno-associated virus type 2 (AAV2) in 11 out of 193 HCC. These AAV2 integrations occurred within known cancer driver genes, namely, CCNA2 (Cyclin A2, 4 cases), TERT (Telomerase Reverse-Transcriptase, 1 case), CCNE1 (Cyclin E1, 3 cases), TNFSF10 (Tumor Necrosis Factor member 10, 2 cases) or KMT2B (Lysine (K)-Specific Methyltransferase 2B, 1 case) leading to over-expression of the target genes. Tumors with viral integration mainly developed in non-cirrhotic liver (9 out of 11 cases) and without known risk factors (6 out of 11) suggesting a pathogenic role of AAV2 in these patients. In conclusion, AAV2 is a DNA virus associated with oncogenic insertional mutagenesis in human HCC.","study_type":"Other","pubmed_ids":[26301494],"external_links":null,"is_released":true,"released_date":"2015-06-09T11:27:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001285","title":"Ribosome_Profiling_of_Macrophages_during_Salmonella_Infection","description":"The aim of this study is to assess translational changes in macrophages over a time course of Salmonella infection.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The aim of this study is to assess translational changes in macrophages over a time course of Salmonella infection.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-10T09:50:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001286","title":"CRISPR__mutations_generation","description":"We generated point mutations in gene promoting cancerogenesis and resistance to anticancer therapy. For this we used CRISPR technology and cancer cell line. To understand percent mutant allelles in population of edited cells, and to see enrichment after drug we need to perform miseq on the amplicon of interest.","abstract":"CRISPR technology allows us to generate point mutations of interest  in the cancer cell lines, for this we use templates with mutations and incorporate them into genome using CRISPR. This is important to validate functions of certain mutations for cancer development and drug resistance.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001287","title":"BLUEPRINT DNA methylation profiles of graft donors in allogenic hematopoietic stem cell transplantation","description":"Allogenic hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological conditions. Acute graft-versus-host disease (aGVHD) is a prevalent immune-mediated complication following HSCT. Current diagnostic biomarkers that correlate with aGVHD severity, progression, and therapy response in graft recipients are insufficient. We investigated whether epigenetic marks measured in peripheral blood of healthy graft donors stratify aGVHD severity in HLA-matched sibling recipients prior to HSCT. We measured genome-wide DNA methylation levels in peripheral blood of 91 HSCT donors using Illumina Infinium HumanMethylation450 BeadChips. We showed that epigenetic signatures underlying aGVHD severity in recipients correspond to immune pathways relevant to aGVHD etiology. We identified distinct DNA methylation marks in graft donors that are associated with aGVHD severity status in recipients. Together, our findings suggest that ‘epigenetic matching’ of HSCT donor-recipient pairs in a clinical setting may be used in conjunction with genetic matching to inform both donor selection and transplantation strategy, with the ultimate aim of improving patient outcome.","abstract":"Allogenic hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological conditions. Acute graft-versus-host disease (aGVHD) is a prevalent immune-mediated complication following HSCT. Current diagnostic biomarkers that correlate with aGVHD severity, progression, and therapy response in graft recipients are insufficient. We investigated whether epigenetic marks measured in peripheral blood of healthy graft donors stratify aGVHD severity in HLA-matched sibling recipients prior to HSCT. We measured genome-wide DNA methylation levels in peripheral blood of 91 HSCT donors using Illumina Infinium HumanMethylation450 BeadChips. We showed that epigenetic signatures underlying aGVHD severity in recipients correspond to immune pathways relevant to aGVHD etiology. We identified distinct DNA methylation marks in graft donors that are associated with aGVHD severity status in recipients. Together, our findings suggest that ‘epigenetic matching’ of HSCT donor-recipient pairs in a clinical setting may be used in conjunction with genetic matching to inform both donor selection and transplantation strategy, with the ultimate aim of improving patient outcome.","study_type":"Other","pubmed_ids":[26669438],"external_links":null,"is_released":true,"released_date":"2015-06-12T10:03:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001288","title":"Induced Pluripotent Cells Derived from Differentiated Rod Photoreceptors Undergo Efficient Retinogenesis in Three-Dimensional Cultures","description":"\"Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are used to study lineage-specific differentiation in culture. We developed a standardized quantitative protocol called STEM-RET to compare eye field specification, optic cup formation, and retinal differentiation across stem cell populations. We reprogrammed individual rod photoreceptors into iPSCs by inducible expression of Oct3/4, Klf4, Sox2, and Myc. We also developed ESC lines from rods by somatic cell nuclear transfer. Using the STEM-RET protocol, we compared the abilities of ESCs, fibroblast-derived iPSCs (f-iPSCs), rod photoreceptor-derived iPSCs (r-iPSCs), and rod photoreceptorderived ESCs to form retinae using STEM-RET. r-iPSCs were the most efficient at producing differentiated retina. Retinae derived from f-iPSCs lacked an inner nuclear layer (INL) and had a concomitant reduction in amacrine cells and other INL cell populations. The INL-specific LIM homeobox gene, Lhx9, was hypermethylated in fiPSCs and concomitantly downregulated in retinae derived from those stem cells. ChIP-seq analysis for H3K36me3, H3K4me1, H3K4me3, H3K9/14Ac, H3K27me3, H3K9me3, CTCF and 5 hydroxymethyl cytosine showed that the major difference between the r-iPSCs and the f-iPSCs were in the genes marked by the CTCF insulator protein. Importantly, CTCF binding enrichment at rod photoreceptor specific genes was at least 10-fold higher in r-iPSCs relative to f-iPSCs. Taken together, our data suggest that both inhibitory and permissive epigenetic marks important for retinal development can be retained in iPSCs and such marks can be exploited to select the most favorable stem cell population to study retinal development or produce photoreceptor precursors for cell transplantation.\"","abstract":"\"Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are used to study lineage-specific differentiation in culture. We developed a standardized quantitative protocol called STEM-RET to compare eye field specification, optic cup formation, and retinal differentiation across stem cell populations. We reprogrammed individual rod photoreceptors into iPSCs by inducible expression of Oct3/4, Klf4, Sox2, and Myc. We also developed ESC lines from rods by somatic cell nuclear transfer. Using the STEM-RET protocol, we compared the abilities of ESCs, fibroblast-derived iPSCs (f-iPSCs), rod photoreceptor-derived iPSCs (r-iPSCs), and rod photoreceptorderived ESCs to form retinae using STEM-RET. r-iPSCs were the most efficient at producing differentiated retina. Retinae derived from f-iPSCs lacked an inner nuclear layer (INL) and had a concomitant reduction in amacrine cells and other INL cell populations. The INL-specific LIM homeobox gene, Lhx9, was hypermethylated in fiPSCs and concomitantly downregulated in retinae derived from those stem cells. ChIP-seq analysis for H3K36me3, H3K4me1, H3K4me3, H3K9/14Ac, H3K27me3, H3K9me3, CTCF and 5 hydroxymethyl cytosine showed that the major difference between the r-iPSCs and the f-iPSCs were in the genes marked by the CTCF insulator protein. Importantly, CTCF binding enrichment at rod photoreceptor specific genes was at least 10-fold higher in r-iPSCs relative to f-iPSCs. Taken together, our data suggest that both inhibitory and permissive epigenetic marks important for retinal development can be retained in iPSCs and such marks can be exploited to select the most favorable stem cell population to study retinal development or produce photoreceptor precursors for cell transplantation.\"","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-12T15:04:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001289","title":"Targeted_Sequencing_of_Human_Myeloid_Malignancies","description":"This study involves targeted sequencing of samples from myeloid malignancies at different timepoints to assess clonal evolution of malignancya.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This study involves targeted sequencing of samples from myeloid malignancies at different timepoints to assess clonal evolution of malignancy","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-17T10:18:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001290","title":"Targetted sequencing of 208 CAKUT related genes.","description":"New prioritization and burden analyses of rare variants in 208 candidate genes are questioning the pathogenicity of previously CAKUT-associated genetic variants  Background: The leading cause of end-stage renal disease in children is attributed to congenital anomalies of the kidney and urinary tract (CAKUT). Familial clustering and mouse models support the presence of monogenic causes. Genetic testing is insufficient as it mainly focuses on HNF1B and PAX2 mutations that are thought to explain CAKUT in 5-15% of patients.   Methods: To identify novel, potentially pathogenic variants in additional genes, we designed a panel of genes identified from studies on familial forms of isolated or syndromic CAKUT and genes suggested by in vitro and in vivo CAKUT models. The coding exons of 208 genes were analyzed in 453 patients with CAKUT using next-generation sequencing. Rare truncating, splice-site variants and non-synonymous variants, predicted to be deleterious and conserved, were prioritized as the most promising variants to have an effect on CAKUT.   Results: Previously reported disease-causing mutations were detected, but only five were fully penetrant causal mutations that improved diagnosis. We prioritized 148 candidate variants in 151 patients, found in 82 genes, for follow up studies. Using a burden test, we found no significant excess of rare variants in any of the genes in our cohort compared to controls.   Conclusions: Thus, in a study that represents the largest set of genes analyzed in CAKUT patients to date, the contribution of previously implicated genes to CAKUT risk is significantly smaller than expected and the disease may be more complex than previously assumed.","abstract":"New prioritization and burden analyses of rare variants in 208 candidate genes are questioning the pathogenicity of previously CAKUT-associated genetic variants  Background: The leading cause of end-stage renal disease in children is attributed to congenital anomalies of the kidney and urinary tract (CAKUT). Familial clustering and mouse models support the presence of monogenic causes. Genetic testing is insufficient as it mainly focuses on HNF1B and PAX2 mutations that are thought to explain CAKUT in 5-15% of patients.   Methods: To identify novel, potentially pathogenic variants in additional genes, we designed a panel of genes identified from studies on familial forms of isolated or syndromic CAKUT and genes suggested by in vitro and in vivo CAKUT models. The coding exons of 208 genes were analyzed in 453 patients with CAKUT using next-generation sequencing. Rare truncating, splice-site variants and non-synonymous variants, predicted to be deleterious and conserved, were prioritized as the most promising variants to have an effect on CAKUT.   Results: Previously reported disease-causing mutations were detected, but only five were fully penetrant causal mutations that improved diagnosis. We prioritized 148 candidate variants in 151 patients, found in 82 genes, for follow up studies. Using a burden test, we found no significant excess of rare variants in any of the genes in our cohort compared to controls.   Conclusions: Thus, in a study that represents the largest set of genes analyzed in CAKUT patients to date, the contribution of previously implicated genes to CAKUT risk is significantly smaller than expected and the disease may be more complex than previously assumed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001291","title":"Aim of project is to examine differences in the genome between basal cell carcinoma tumor and normal skin, and to better understand the types of mutations that occur as a tumor progresses from basaloid histology to more squamatized","description":"na","abstract":"na","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001292","title":"SNP genotyping data in genes related to trace element homeostasis","description":"In this study we provide data regarding sample charactheristics and genotypes in 150 human samples of European origin for SNPs located around genes related to metal homeostasis. SNPs were genotyped with the Illumina VeraCode technology (192-plex format). The genotyped SNPs were used to identify quantitative trait loci in the same samples. Data referring to the quantification of 18 micronutrients, the expression levels of 90 genes and the protein abundances of 40 proteins related to metal homeostasis in the same samples are directly available as supplementary material in the publication of this study.","abstract":"In this study we provide data regarding sample charactheristics and genotypes in 150 human samples of European origin for SNPs located around genes related to metal homeostasis. SNPs were genotyped with the Illumina VeraCode technology (192-plex format). The genotyped SNPs were used to identify quantitative trait loci in the same samples. Data referring to the quantification of 18 micronutrients, the expression levels of 90 genes and the protein abundances of 40 proteins related to metal homeostasis in the same samples are directly available as supplementary material in the publication of this study.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-19T08:49:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001293","title":"Growth Hormone (GH) -secreting Pituitary Adenoma","description":"Data from 12 fresh-frozen somatotropinomas and their corresponding blood samples. Details are given in Valimaki et al. Whole-genome sequencing of Growth Hormone (GH) -secreting Pituitary Adenoma. Provisionally accepted, 2015.","abstract":"Data from 12 fresh-frozen somatotropinomas and their corresponding blood samples. Details are given in Valimaki et al. Whole-genome sequencing of Growth Hormone (GH) -secreting Pituitary Adenoma. Provisionally accepted, 2015.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-22T10:00:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001294","title":"Transcriptome_human_nasal_epithelium","description":"1. Odors are detected, firstly, by olfactory sensory neurons (OSNs) in the olfactory epithelium of the nose. This neurons then project directly to the olfactory bulb in the brain. Olfaction depends on cellular regeneration of the OE, olfactory bulb and hippocampus, and on their continual re-wiring. The olfactory neural pathway includes regions of the frontal, temporal and limbic brain, which in turn overlap with brain areas involved in brain disorders. OSNs are the only aspect of the human brain exposed to the external environment. This not only makes them vulnerable to environmental changes, but also accessible for biomedical studies.We have already sequenced and developed a protocol for analyzing the transcriptome of mouse main olfactory epithelium and single OSNs. We propose here to perform a similar study for samples from the human olfactory epithelium. We have developed a minimally invasive method for obtaining human OSNs, among other cells from the nasal epithelium. In this experiment, we have obtained cell samples from the olfactory epithelium, including OSN, from healthy volunteers. We would like to further characterize them by RNA sequencing. This will give us valuable insight into human olfaction. It will also provide a first step into a new avenue to study, and find biomarkers for, brain diseases though the analysis of these easily available neurons.   This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Olfactory sensory neurons (OSN) in the olfactory epithelium of the nose are responsible for detecting odours. In this experiment, we have obtained cell samples from the olfactory epithelium, including OSN, from healthy volunteers. We will identify the transcriptional pattern of these cells by RNA sequencing using the Illumina platform. The analysis will help us further understand human olfaction.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-22T13:20:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001295","title":"Study title","description":"Study abstract","abstract":"Study abstract","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001296","title":"Integrated molecular analysis of adult T-cell leukemia/lymphoma","description":"This study is an integrated molecular study of adult T-cell leukemia/lymphoma which includes whole-exome (n = 81), whole-genome (n = 48), and transcriptome sequencing data (n = 57) as well as methylation (n = 109) and SNP array data (n = 426)","abstract":"This study is an integrated molecular study of adult T-cell leukemia/lymphoma which includes whole-exome (n = 81), whole-genome (n = 48), and transcriptome sequencing data (n = 57) as well as methylation (n = 109) and SNP array data (n = 426)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-22T18:26:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001297","title":"Comprehensive analysis of the (epi)genome of pediatric atypical teratoid/rhabdoid tumours (AT/RTs)","description":"Whole exome sequencing of atypical teratoid /rhabdoid tumors (AT/RTs) revealed recurrent mutations only in SMARCB1, a gene involved in chromatin remodeling. However, preliminary data from our lab using gene expression and DNA methylation arrays shows that there are three distinct molecular subgroups of AT/RTs, suggesting that other molecular alterations underlying the development of these aggressive pediatric brain tumors must be found outside the coding genome or at the epigenomic level. Identification of these (epi)genomic alterations, which we intend to address in this project, may lead to novel treatment strategies for these tumors and reveal options for meaningful patient stratification.","abstract":"Whole exome sequencing of atypical teratoid /rhabdoid tumors (AT/RTs) revealed recurrent mutations only in SMARCB1, a gene involved in chromatin remodeling. However, preliminary data from our lab using gene expression and DNA methylation arrays shows that there are three distinct molecular subgroups of AT/RTs, suggesting that other molecular alterations underlying the development of these aggressive pediatric brain tumors must be found outside the coding genome or at the epigenomic level. Identification of these (epi)genomic alterations, which we intend to address in this project, may lead to novel treatment strategies for these tumors and reveal options for meaningful patient stratification.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-23T07:58:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001298","title":"HipSci_30x_whole_genome_sequencing_of_iPSC_reference_set","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform  high coverage whole genome sequencing using the Illumina HiSeq X Ten system.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform  high coverage whole genome sequencing using the Illumina HiSeq X Ten system.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001299","title":"Multiple_Myeloma_Diagnosis_to_Relapse_study_samples","description":"The study will investigate serial samples from the same patient taken at the time of MGUS or SMM diagnosis, and later at the time of evolution towards MM. Samples will be sequenced by whole genome along with a matched normal to obtain the highest possible amount of information toinvestigate genomic changes at disease evolution.","abstract":"A key question in cancer biology is how a cell transforms from an essentially benign premalignant condition to a malignant invasive state. Some hints as to how this happens can come from the study of multiple myeloma (MM), which is characterized by the prolifera- tion of abnormal plasma cells (PC)1 that have fewer mutations than the more complex solid tumors and as such provides a good model in which to address the question of cancer progression. Current understanding of MM development is thought to involve a multistep transformation process, occurring as a consequence of the sequential acquisition of genetic hits that deregulate the behavior of a normal PC. The first stage of this process is a benign premalignant condition, known as monoclonal gammo- pathy of undetermined significance (MGUS) that transforms to MM at a rate of 1% per annum. The next step of MM evolution is the development of smoldering myeloma (SMM) that shares the same morphological features as symptomatic MM, but lacks evidence of end-organ damage and progresses to MM at a rate of 10% per annum. In the final stage of the transformation process, the malignant PC clone gains independence from the bone marrow (BM) microenvironment, presenting either as PC leukemia (PCL) or as extra-medullary myeloma.Translocations, involving the immunoglobulin heavy-chain (IGH) locus, or hyperdiploidy are seen as primary events in myeloma that are present in 100% of cells but these alone are not sufficient to result in clinically invasive myeloma, given that they can be found in patients with MGUS and may be stable for many years. Therefore, there must be additional genetic events, which contribute toward disease progression leading to the invasive stages of the disease. An elegant way of accurately defining the genetic factors associated with disease progression is to study sequential samples from the same patient as they progress from one clinical stage to another. Here, we aim at sequencing the whole genome of a number of patient with serial samples to accurately characterise the evolution of the genomic landscape of the various disease stages, by defining the mutations, copy number changes, and translocations that more frequently are represented in the pre-malignant vs malignant stages.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-25T15:42:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001300","title":"Mutational_landscape_of_mesothelioma_PDX_models","description":"Mutation profiling of mesothelioma PDX samples using the Sanger V3 Agilent capture design.","abstract":"Mutation profiling of mesothelioma PDX samples using the Sanger V3 Agilent capture design.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001301","title":"PRDM9_loss_of_function_follow_up_from_Born_in_Bradford_Autozygosity_sequencing","description":"In the autozygosity exome sequencing of Born-in-Bradford samples of Pakistani origin thereis a mother who is homozygous for an apparent truncating stop codon in PRDM9, the generesponsible for localising recombination during meiosis. We plan to deep sequence motherand child with X10, and physically phase the mother with PacBio sequencing.We will use this data to identify recombination locations, and test whether these areconsistent with the known fine scale recombination map.","abstract":"In the autozygosity exome sequencing of Born-in-Bradford samples of Pakistani origin thereis a mother who is homozygous for an apparent truncating stop codon in PRDM9, the generesponsible for localising recombination during meiosis. We plan to deep sequence motherand child with X10, and physically phase the mother with PacBio sequencing.We will use this data to identify recombination locations, and test whether these areconsistent with the known fine scale recombination map.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-25T16:34:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001302","title":"Identification of four new susceptibility loci for testicular germ cell tumour, including variants near GAB2, GSPT1 and ZFPM1","description":"Genome wide association studies (GWAS) have identified multiple risk loci for testicular germ cell tumour (TGCT), revealing a polygenic model of disease susceptibility strongly influenced by common variation. To identify further SNPs associated with TGCT we conducted a multistage GWAS with a combined dataset of &gt;25,000 individuals (6,059 cases and 19,094 controls). We identified new risk loci for TGCT at 3q23 (rs11705932, TFDP2, P = 1.5 x 10-9), 11q14.1 (rs7107174, GAB2, P = 9.7 x 10-11), 16p13.13 (rs4561483, GSPT1, P = 1.6 x 10-8) and 16q24.2 (rs55637647, ZFPM1, P = 3.4 x 10-9). We additionally present detailed functional analysis of these loci, identifying a statistically significant relationship between rs4561483 risk genotype and increased GSPT1 expression in TGCT patient samples. These findings provide additional support for a polygenic model of TGCT risk and further insight into the biological basis of disease development.","abstract":"Genome wide association studies (GWAS) have identified multiple risk loci for testicular germ cell tumour (TGCT), revealing a polygenic model of disease susceptibility strongly influenced by common variation. To identify further SNPs associated with TGCT we conducted a multistage GWAS with a combined dataset of &gt;25,000 individuals (6,059 cases and 19,094 controls). We identified new risk loci for TGCT at 3q23 (rs11705932, TFDP2, P = 1.5 x 10-9), 11q14.1 (rs7107174, GAB2, P = 9.7 x 10-11), 16p13.13 (rs4561483, GSPT1, P = 1.6 x 10-8) and 16q24.2 (rs55637647, ZFPM1, P = 3.4 x 10-9). We additionally present detailed functional analysis of these loci, identifying a statistically significant relationship between rs4561483 risk genotype and increased GSPT1 expression in TGCT patient samples. These findings provide additional support for a polygenic model of TGCT risk and further insight into the biological basis of disease development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-30T17:38:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001303","title":"Accurate sample assignment in a multiplexed, ultra-sensitive, high-throughput sequencing assay for minimal residual disease","description":"High throughput sequencing (HTS) (next generation sequencing) of the rearranged immunoglobulin and T-cell receptor genes promises to be cheaper and more sensitive than current methods for monitoring minimal residual disease (MRD) in patients with acute lymphoblastic leukemia. However, adoption of new approaches by clinical laboratories requires careful evaluation of all potential sources of error and the development of strategies to ensure the highest accuracy. Timely and efficient clinical use of HTS platforms will depend on combining multiple samples (multiplexing) in each sequencing run. Here we examine immunoglobulin heavy chain gene HTS on the Illumina MiSeq platform for MRD (HTS-MRD). We identify errors associated with multiplexing that could potentially impact on the accuracy of MRD analysis. We optimise a strategy combining high purity, sequence-optimised oligonucleotides, dual-indexing and an error-aware demultiplexing approach to minimise errors and maximise sensitivity. We present a probability-based demultiplexing pipeline, Error-Aware Demultiplexer (EAD) - that is suitable for all MiSeq sequencing strategies and accurately assigns samples to the correct identifier without excessive loss of data. Finally using controls quantified by digital PCR, we show that HTS-MRD can accurately detect as few as 1 in 106 copies of specific leukemic MRD.","abstract":"High throughput sequencing (HTS) (next generation sequencing) of the rearranged immunoglobulin and T-cell receptor genes promises to be cheaper and more sensitive than current methods for monitoring minimal residual disease (MRD) in patients with acute lymphoblastic leukemia. However, adoption of new approaches by clinical laboratories requires careful evaluation of all potential sources of error and the development of strategies to ensure the highest accuracy. Timely and efficient clinical use of HTS platforms will depend on combining multiple samples (multiplexing) in each sequencing run. Here we examine immunoglobulin heavy chain gene HTS on the Illumina MiSeq platform for MRD (HTS-MRD). We identify errors associated with multiplexing that could potentially impact on the accuracy of MRD analysis. We optimise a strategy combining high purity, sequence-optimised oligonucleotides, dual-indexing and an error-aware demultiplexing approach to minimise errors and maximise sensitivity. We present a probability-based demultiplexing pipeline, Error-Aware Demultiplexer (EAD) - that is suitable for all MiSeq sequencing strategies and accurately assigns samples to the correct identifier without excessive loss of data. Finally using controls quantified by digital PCR, we show that HTS-MRD can accurately detect as few as 1 in 106 copies of specific leukemic MRD.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-06-30T23:06:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001304","title":"Resistance_to_MAPK_inhibitor_induces_internal_duplication_in_BRAF","description":"2 BRAFV600E cell lines that have been made resistance to 1. the BRAF inhibitor PLX4720 and 2. the combination therapy of dabrafenib and trametinib seem to have a internal duplication in the kinase domain. We would like to know if this is caused by a translocation.","abstract":"2 BRAFV600E cell lines that have been made resistance to 1. the BRAF inhibitor PLX4720 and 2. the combination therapy of dabrafenib and trametinib seem to have a internal duplication in the kinase domain. We would like to know if this is caused by a translocation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-07-01T10:52:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001305","title":"The Genomic Landscape of Response to EGFR Blockade  in Colorectal Cancer","description":"Colorectal cancer (CRC) is the third most common cancer world-wide with 1.2 million patients diagnosed yearly.  In late stage CRC, the most commonly used targeted therapies are monoclonal antibodies cetuximab and panitumumab, which inactivate EGFR.  Recent studies have identified alterations in KRAS and other genes as likely mechanisms of primary and secondary resistance to anti-EGFR antibody therapy.  Despite these efforts, additional mechanisms of resistance to EGFR blockade are thought to be present in CRC and little is known about determinants of sensitivity to this therapy.  To examine the effect of somatic genetic changes in CRC on response to anti-EGFR antibody therapy, we performed complete exome sequence and copy number analyses of 129 patient-derived tumorgrafts and targeted genomic analyses of 55 patient tumors, all of which were KRAS wild-type.  We analyzed the response of tumors to anti-EGFR antibody blockade in tumorgraft models or in clinical settings.  In addition to previously identified genes, we detected mutations in ERBB2, EGFR, FGFR1, PDGFRA, and MAP2K1 as potential mechanisms of primary resistance to this therapy.  Novel alterations in the ectodomain of EGFR were identified in patients with acquired resistance to EGFR blockade.  Amplifications and sequence changes in the tyrosine kinase receptor adaptor gene IRS2 were identified in tumors with increased sensitivity to anti-EGFR therapy.  Therapeutic resistance to EGFR blockade could be overcome in tumorgraft models through combinatorial therapies targeting actionable genes.  These analyses provide a systematic approach to evaluate response to targeted therapies in human cancer, highlight new mechanisms of responsiveness to anti-EGFR therapies, and provide new avenues for intervention in the management of CRC.","abstract":"Colorectal cancer (CRC) is the third most common cancer world-wide with 1.2 million patients diagnosed yearly.  In late stage CRC, the most commonly used targeted therapies are monoclonal antibodies cetuximab and panitumumab, which inactivate EGFR.  Recent studies have identified alterations in KRAS and other genes as likely mechanisms of primary and secondary resistance to anti-EGFR antibody therapy.  Despite these efforts, additional mechanisms of resistance to EGFR blockade are thought to be present in CRC and little is known about determinants of sensitivity to this therapy.  To examine the effect of somatic genetic changes in CRC on response to anti-EGFR antibody therapy, we performed complete exome sequence and copy number analyses of 129 patient-derived tumorgrafts and targeted genomic analyses of 55 patient tumors, all of which were KRAS wild-type.  We analyzed the response of tumors to anti-EGFR antibody blockade in tumorgraft models or in clinical settings.  In addition to previously identified genes, we detected mutations in ERBB2, EGFR, FGFR1, PDGFRA, and MAP2K1 as potential mechanisms of primary resistance to this therapy.  Novel alterations in the ectodomain of EGFR were identified in patients with acquired resistance to EGFR blockade.  Amplifications and sequence changes in the tyrosine kinase receptor adaptor gene IRS2 were identified in tumors with increased sensitivity to anti-EGFR therapy.  Therapeutic resistance to EGFR blockade could be overcome in tumorgraft models through combinatorial therapies targeting actionable genes.  These analyses provide a systematic approach to evaluate response to targeted therapies in human cancer, highlight new mechanisms of responsiveness to anti-EGFR therapies, and provide new avenues for intervention in the management of CRC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-07-01T20:39:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001306","title":"Integrated Genomic Analysis of Chronic Lymphocytic Leukaemia","description":"Chronic lymphocytic leukaemia (CLL) is a frequent and heterogeneous disease whose genetic alterations determining the clinicobiological behaviour are not fully understood. Here, we describe a comprehensive evaluation of the genomic landscape of 452 CLLs and 54 monoclonal B-lymphocytosis (MBL), a precursor disorder.  This study provides an integrated portrait of the genomic landscape of CLL, identifies new recurrent mutations acting as drivers of the disease, and suggests clinical interventions which may improve the management of patients with this neoplasia.\nThe data here included was described in the ICGC-CLL manuscript published by Puente et al (Nature 2015). Note that complementary RNA-seq data generated within the IGCG-CLL can be found in EGAS00001000374.","abstract":"Chronic lymphocytic leukaemia (CLL) is a frequent and heterogeneous disease whose genetic alterations determining the clinicobiological behaviour are not fully understood. Here, we describe a comprehensive evaluation of the genomic landscape of 452 CLLs and 54 monoclonal B-lymphocytosis (MBL), a precursor disorder.  This study provides an integrated portrait of the genomic landscape of CLL, identifies new recurrent mutations acting as drivers of the disease, and suggests clinical interventions which may improve the management of patients with this neoplasia.\nThe data here included was described in the ICGC-CLL manuscript published by Puente et al (Nature 2015). Note that complementary RNA-seq data generated within the IGCG-CLL can be found in EGAS00001000374.","study_type":"Other","pubmed_ids":[26200345],"external_links":null,"is_released":true,"released_date":"2015-07-02T13:56:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001307","title":"Population_Genetic_studies_of_Caucasus_populations","description":"Whole genome sequences at high-coverage (&gt;30x) of 12 individuals from the Caucasus forpopulation-genetic studies.","abstract":"Whole genome sequences at high-coverage (&gt;30x) of 12 individuals from the Caucasus forpopulation-genetic studies.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001308","title":"Telomerase activation by genomic rearrangements in high-risk neuroblastoma","description":"Neuroblastoma is a malignant pediatric tumor of the sympathetic nervous system1. Roughly half of these tumors regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavorable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive2-4. We have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n=39; low-risk, n=17) and discovered recurrent genomic rearrangements affecting a chromosomal region (5p15.22) proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumor type1,2,5. In an extended case series (n=217), TERT rearrangements defined a subgroup of high-risk tumors with particularly poor outcome. Despite the large diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumors, TERT expression was also elevated in MYCN-amplified tumors, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.22 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodeling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cells bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodeling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the center of transformation in a large fraction of these tumors.","abstract":"Neuroblastoma is a malignant pediatric tumor of the sympathetic nervous system1. Roughly half of these tumors regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavorable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive2-4. We have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n=39; low-risk, n=17) and discovered recurrent genomic rearrangements affecting a chromosomal region (5p15.22) proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumor type1,2,5. In an extended case series (n=217), TERT rearrangements defined a subgroup of high-risk tumors with particularly poor outcome. Despite the large diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumors, TERT expression was also elevated in MYCN-amplified tumors, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.22 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodeling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cells bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodeling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the center of transformation in a large fraction of these tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-07-06T12:18:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001309","title":"Comparative genomic analysis of colorectal cancer in different stage","description":"22 WGS and 18 WES of colorectal cancer cases","abstract":"22 WGS and 18 WES of colorectal cancer cases","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001310","title":"Barcoding reveals complex clonal dynamics of de novo transformed human mammary cells","description":"Most human breast cancers have already diversified genomically when they first become clinically evident, by which time extensive heterogeneous histopathologies, transcriptomes and growth patterns are also apparent. Accordingly, important initial events and the cellular context in which they occur have been difficult to characterize. Using DNA barcoding, we now demonstrate the high efficiency with which both purified basal and luminal cells isolated directly from normal adult human mammary tissue can be rapidly transformed by a single oncogene (KRASG12D) resulting in the production within 8 weeks in vivo of serially transplantable, polyclonal, invasive ductal carcinomas that are phenotypically heterogeneous and transcriptionally distinct from the initial cells transduced. Barcoding also revealed a consistent dramatic change in the clonal content of passaged tumours. This system thus provides a powerful new platform for examining early events in the genesis, evolution and treatment response of malignant human mammary cells generated using defined mutations.","abstract":"Most human breast cancers have already diversified genomically when they first become clinically evident, by which time extensive heterogeneous histopathologies, transcriptomes and growth patterns are also apparent. Accordingly, important initial events and the cellular context in which they occur have been difficult to characterize. Using DNA barcoding, we now demonstrate the high efficiency with which both purified basal and luminal cells isolated directly from normal adult human mammary tissue can be rapidly transformed by a single oncogene (KRASG12D) resulting in the production within 8 weeks in vivo of serially transplantable, polyclonal, invasive ductal carcinomas that are phenotypically heterogeneous and transcriptionally distinct from the initial cells transduced. Barcoding also revealed a consistent dramatic change in the clonal content of passaged tumours. This system thus provides a powerful new platform for examining early events in the genesis, evolution and treatment response of malignant human mammary cells generated using defined mutations.","study_type":"Other","pubmed_ids":[26633636],"external_links":null,"is_released":true,"released_date":"2015-07-09T20:15:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001311","title":"Genome-wide study of resistance to severe malaria in eleven worldwide populations","description":"A genome-wide study of resistance to severe malaria in 18,000 samples from eleven worldwide populations, including eight populations sub-Saharan Africa.","abstract":"A genome-wide study of resistance to severe malaria in 18,000 samples from eleven worldwide populations, including eight populations sub-Saharan Africa.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-07-13T11:13:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001312","title":"Thu_Jul_16_09:32:53_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001313","title":"Thu_Jul_16_09:33:51_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001314","title":"Genetic landscape of pediatric ETV6-RUNX1 acute lymphoblastic leukemia","description":"Abstract in preparation","abstract":"Abstract in preparation","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-18T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001315","title":"Genetic landscape of pediatric ETV6-RUNX1 acute lymphoblastic leukemia","description":"Abstract in preparation","abstract":"Abstract in preparation","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-18T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001316","title":"Genetic landscape of pediatric high hyperdiploid acute lymphoblastic leukemia","description":"Abstract in preparation","abstract":"Abstract in preparation","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-18T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001317","title":"Genomic landscape of childhood acute lymphoblastic leukemia","description":"Abstract in preparation","abstract":"Abstract in preparation","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-18T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001318","title":"HipSci___RNAseq___Rare_BBS","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bardet-Biedl syndrome \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bardet-Biedl syndrome","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-07-22T10:32:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001319","title":"HAP1_DNA_repair_deficient_lines","description":"This study is to look at mutational signatures in a haploid iPS lines carrying frame-shift mutations in DNA repair genes. This will help establish causative roles for particular signatures.","abstract":"This study is to look at mutational signatures in a haploid iPS lines carrying frame-shift mutations in DNA repair genes. This will help establish causative roles for particular signatures.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001320","title":"PRDM9_loss_of_function_follow_up_from_Born_in_Bradford_Autozygosity_sequencing","description":"In the autozygosity exome sequencing of Born-in-Bradford samples of Pakistani origin thereis a mother who is homozygous for an apparent truncating stop codon in PRDM9, the generesponsible for localising recombination during meiosis.  We plan to deep sequence motherand child with X10, and physically phase the mother with PacBio sequencing.We will use this data to identify recombination locations, and test whether these areconsistent with the known fine scale recombination map.","abstract":"In the autozygosity exome sequencing of Born-in-Bradford samples of Pakistani origin thereis a mother who is homozygous for an apparent truncating stop codon in PRDM9, the generesponsible for localising recombination during meiosis.  We plan to deep sequence motherand child with X10, and physically phase the mother with PacBio sequencing.We will use this data to identify recombination locations, and test whether these areconsistent with the known fine scale recombination map.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001321","title":"Whole-genome plasma sequencing reveals focal amplifications as driving force in metastatic prostate cancer","description":"Genomic alterations in metastatic prostate cancer remain incompletely characterized1-7. We analyzed 493 prostate cancer cases from the TCGA database and performed whole-genome plasma sequencing8-10 of 95 plasma samples derived from 43 patients with metastatic prostate cancer and 50 control samples from male individuals without malignant disease. Although the prostate cancer genome was reported to be characterized by relatively few focal chromosomal alterations11, we demonstrate that newly occurring focal amplifications are a driving force in the progression to lethal, metastatic prostate cancer. We identified established driver aberrations in a cancer-related gene in nearly all cases (97.7%), including driver gene fusions (TMPRSS2:ERG), driver focal deletions (PTEN, RYBP, SHQ1), and driver amplifications (AR, MYC). In serial plasma analyses of samples with comparable circulating tumor DNA allele frequency, we observed changes in focal amplifications in 40% of cases. The mean time interval between new alterations was 26.4 weeks (range: 5-52 weeks), suggesting that these copy number changes are rapid adaptations to selection pressure. In contrast to earlier reports that lethal metastatic disease is clonal12-14, we show that increase of neuron-specific enolase was accompanied by clonal pattern changes in the tumor genome. Our analyses have significant implications for the clinical management of prostate cancer.","abstract":"Genomic alterations in metastatic prostate cancer remain incompletely characterized1-7. We analyzed 493 prostate cancer cases from the TCGA database and performed whole-genome plasma sequencing8-10 of 95 plasma samples derived from 43 patients with metastatic prostate cancer and 50 control samples from male individuals without malignant disease. Although the prostate cancer genome was reported to be characterized by relatively few focal chromosomal alterations11, we demonstrate that newly occurring focal amplifications are a driving force in the progression to lethal, metastatic prostate cancer. We identified established driver aberrations in a cancer-related gene in nearly all cases (97.7%), including driver gene fusions (TMPRSS2:ERG), driver focal deletions (PTEN, RYBP, SHQ1), and driver amplifications (AR, MYC). In serial plasma analyses of samples with comparable circulating tumor DNA allele frequency, we observed changes in focal amplifications in 40% of cases. The mean time interval between new alterations was 26.4 weeks (range: 5-52 weeks), suggesting that these copy number changes are rapid adaptations to selection pressure. In contrast to earlier reports that lethal metastatic disease is clonal12-14, we show that increase of neuron-specific enolase was accompanied by clonal pattern changes in the tumor genome. Our analyses have significant implications for the clinical management of prostate cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001322","title":"Study_of_the_effect_of_mutant_Nucleophosmin__Npm1c__on_miRNA_expression","description":"This will be done in two ways: 1. Study GEP in blood cells of Npm1c mice and 2. Study the short term effects of transfected mutant and wild-type Npm1 on cellular mRNA and miRNA levels in haemopoietic cell line K562.. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Acute Myeloid Leukaemia (AML) is a devastating disease with a poor prognosis. The largest subgroup of AML, representing 30-35% of all cases, is characterised by mutations in NPM1, the gene for Nucleophosmin [1]. Over the last 4 years I developed and studied a humanised knock-in mouse model of NPM1c mutations and combined this with insertional mutagenesis using a novel Sleeping Beauty transposon. Key results include the findings that Npm1c mutations cause Hox overexpression and collaborate with activating mutations in Ras pathway genes to cause AML.  The aim of the proposed work is to investigate the mechanism of Hox overexpression in Npm1c+ve blood cells. It has been suggested that changes in cellular miRNA levels may underlie this effect [2] and striking new evidence that Nucleophosmin can bind and stabilise miRNAs gives this hypothesis credence [3]. I want to generate gene expression profile data (mRNA and miRNA) to support or refute this hypothesis. References:[1] Falini et al. NEJM 2005; 352:254 [2] Garzon et al. PNAS 2005; 105:3945. [3] Wang et al, Nucleic Acids Res 2010; Epub, PMID: 20615901.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001323","title":"Whole_Genome_Sequencing_of_JK_Family","description":"In collaboration with Dr David Savage, we have identified a patient with a very unusualphenotype, lacking almost all visceral fat, but showing a massive accumulation of white fattissue behind her neck and significantly elevated liver fat.Whole exome sequencing of the proband and her unaffected parents and brother has beenrun previously, however no causative variant has been found and the sequencing coveragewas generally poor. We propose to conduct whole genome sequencing of all 4 familymembers at a depth of 30X.","abstract":"In collaboration with Dr David Savage, we have identified a patient with a very unusualphenotype, lacking almost all visceral fat, but showing a massive accumulation of white fattissue behind her neck and significantly elevated liver fat.Whole exome sequencing of the proband and her unaffected parents and brother has beenrun previously, however no causative variant has been found and the sequencing coveragewas generally poor. We propose to conduct whole genome sequencing of all 4 familymembers at a depth of 30X.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-07-23T13:54:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001324","title":"JMML targeted sequencing (2013)","description":"Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic myeloproliferative neoplasm of early childhood initiated by germline or somatic RAS-activating mutations (Chang, Dvorak et al. 2014). Clinical evolution is heterogeneous, with acute myeloid leukemia (AML) transformation in 1/3 of cases and frequent relapses after hematopoietic-stem-cell transplantation (HSCT), although some patients experience spontaneous remission (Locatelli, Nollke et al. 2005; Matsuda, Shimada et al. 2007; Takagi, Piao et al. 2013; Locatelli and Niemeyer 2015). The initiating lesion incompletely predicts outcome, suggesting the involvement of additional mutations. Genetic profiling of a large JMML cohort (n=118), including whole-exome sequencing (WES) in 30 cases, uncovered additional genetic abnormalities in 56 cases (47%). Somatic events were rare (0.38/case/Mb) and restricted to sporadic (47/78; 60%) or NF1-associated (8/8; 100%) JMML. Multiple concomitant genetic hits were identified targeting the RAS pathway in 13/78 (17%), RAC2D63V, which activates the PI3K/PDK1/AKT and the mTORC2 pathways, and a novel pathway for JMML, the polycomb repressive complex 2 (PRC2), in 26/78 (33%) of the sporadic JMML cases. Interestingly, PRC2 imbalance was recently shown to synergize with RAS activation (De Raedt, Beert et al. 2014). JMML outcome was associated to the mutational profile, suggesting a dose-dependent effect for RAS-pathway activation, distinguishing very aggressive JMML rapidly progressing to AML.","abstract":"Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic myeloproliferative neoplasm of early childhood initiated by germline or somatic RAS-activating mutations (Chang, Dvorak et al. 2014). Clinical evolution is heterogeneous, with acute myeloid leukemia (AML) transformation in 1/3 of cases and frequent relapses after hematopoietic-stem-cell transplantation (HSCT), although some patients experience spontaneous remission (Locatelli, Nollke et al. 2005; Matsuda, Shimada et al. 2007; Takagi, Piao et al. 2013; Locatelli and Niemeyer 2015). The initiating lesion incompletely predicts outcome, suggesting the involvement of additional mutations. Genetic profiling of a large JMML cohort (n=118), including whole-exome sequencing (WES) in 30 cases, uncovered additional genetic abnormalities in 56 cases (47%). Somatic events were rare (0.38/case/Mb) and restricted to sporadic (47/78; 60%) or NF1-associated (8/8; 100%) JMML. Multiple concomitant genetic hits were identified targeting the RAS pathway in 13/78 (17%), RAC2D63V, which activates the PI3K/PDK1/AKT and the mTORC2 pathways, and a novel pathway for JMML, the polycomb repressive complex 2 (PRC2), in 26/78 (33%) of the sporadic JMML cases. Interestingly, PRC2 imbalance was recently shown to synergize with RAS activation (De Raedt, Beert et al. 2014). JMML outcome was associated to the mutational profile, suggesting a dose-dependent effect for RAS-pathway activation, distinguishing very aggressive JMML rapidly progressing to AML.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-07-23T15:37:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001325","title":"Fri_Jul_24_11:53:46_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001326","title":"Fri_Jul_24_11:54:36_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001327","title":"Fri_Jul_24_17:03:29_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001328","title":"Mon_Jul_27_08:57:24_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001329","title":"Carcinoma of the oral tongue (OTSCC) genomic landscape characterisation","description":"Carcinoma of the oral tongue (OTSCC) is the most common malignancy of the oral cavity, characterized by frequent recurrence and poor survival. The last three decades has witnessed a change in the OTSCC epidemiological profile, with increasing incidence in younger patients, females and never-smokers. Here, we sought to characterize the OTSCC genomic landscape and to determine factors that may delineate the genetic basis of this disease, inform prognosis and identify targets for therapeutic intervention.","abstract":"Carcinoma of the oral tongue (OTSCC) is the most common malignancy of the oral cavity, characterized by frequent recurrence and poor survival. The last three decades has witnessed a change in the OTSCC epidemiological profile, with increasing incidence in younger patients, females and never-smokers. Here, we sought to characterize the OTSCC genomic landscape and to determine factors that may delineate the genetic basis of this disease, inform prognosis and identify targets for therapeutic intervention.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-07-27T09:43:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001330","title":"Mon_Jul_27_12:07:36_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001331","title":"Mon_Jul_27_12:08:35_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001332","title":"A collection of 142 samples used to evaluate the sensitivity and specificity of small-scale variation detection in exome-capture data with a particular focus on indel detection.","description":"The dataset includes exome sequencing data and 704 Sanger sequencing validations for the 142 samples. The 704 Sanger sequencing validations are comprised of 416 variants and 288 sites known to be negative, including 293 indels and 247 negative indel sites.  DNA libraries were prepared from genomic DNA using the Illumina TruSeq sample preparation kit. DNA was fragmented using Covaris technology and the libraries were prepared without gel size selection. Target enrichment was performed in pools of six libraries using the Illumina TruSeq Exome Enrichment kit. The captured DNA libraries were PCR amplified using the supplied paired-end PCR primers. Sequencing was performed with an Illumina HiSeq2000 (v3 flow cell, one pool per lane) generating 2x101-bp reads. Technology – Illumina HiSeq 2000","abstract":"The dataset includes exome sequencing data and 704 Sanger sequencing validations for the 142 samples. The 704 Sanger sequencing validations are comprised of 416 variants and 288 sites known to be negative, including 293 indels and 247 negative indel sites.  DNA libraries were prepared from genomic DNA using the Illumina TruSeq sample preparation kit. DNA was fragmented using Covaris technology and the libraries were prepared without gel size selection. Target enrichment was performed in pools of six libraries using the Illumina TruSeq Exome Enrichment kit. The captured DNA libraries were PCR amplified using the supplied paired-end PCR primers. Sequencing was performed with an Illumina HiSeq2000 (v3 flow cell, one pool per lane) generating 2x101-bp reads. Technology – Illumina HiSeq 2000","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-07-27T14:25:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001333","title":"melanoma","description":"melanoma","abstract":"melanoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001334","title":"Mon_Jul_27_16:21:42_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001335","title":"Mon_Jul_27_16:27:18_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001336","title":"Mon_Jul_27_16:38:00_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001337","title":"Tue_Jul_28_16:15:00_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001338","title":"Tue_Jul_28_16:16:38_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001339","title":"Anaplastic oligodendroglioma exome and RNA sequencing data","description":"Anaplastic oligodendrogliomas (AOs) are rare primary brain tumors which are generally incurable, with heterogeneous prognosis and few treatment targets identified. Most oligodendrogliomas have chromosome 1p/19q co-deletion and IDH mutation. We analyzed 51 AOs by whole-exome sequencing, identifying previously reported frequent somatic mutations in CIC and FUBP1. We also identified recurrent mutations in TCF12 and in an additional series of 83 AO. Overall 7.5% of AO are mutated for TCF12, which encodes an oligodendrocyte-related transcription factor. 80% of TCF12 mutations identified were in either the bHLH domain, which is important for TCF12 function as a transcription factor, or were frame shift mutations leading to TCF12 truncated for this domain. We show that these mutations compromise TCF12 transcriptional activity and are associated with a more aggressive tumor type. Our analysis provides further insights into the unique and shared pathways driving AO.","abstract":"Anaplastic oligodendrogliomas (AOs) are rare primary brain tumors which are generally incurable, with heterogeneous prognosis and few treatment targets identified. Most oligodendrogliomas have chromosome 1p/19q co-deletion and IDH mutation. We analyzed 51 AOs by whole-exome sequencing, identifying previously reported frequent somatic mutations in CIC and FUBP1. We also identified recurrent mutations in TCF12 and in an additional series of 83 AO. Overall 7.5% of AO are mutated for TCF12, which encodes an oligodendrocyte-related transcription factor. 80% of TCF12 mutations identified were in either the bHLH domain, which is important for TCF12 function as a transcription factor, or were frame shift mutations leading to TCF12 truncated for this domain. We show that these mutations compromise TCF12 transcriptional activity and are associated with a more aggressive tumor type. Our analysis provides further insights into the unique and shared pathways driving AO.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001340","title":"Genomic analysis of HPV positive versus HPV negative esophageal adenocarcinoma","description":"High-risk human papillomavirus (hr-HPV) has been implicated in a subset of patients with esophageal adenocarcinoma (EAC). We therefore hypothesized that HPV associated EAC may have distinct genomic aberrations compared with viral negative esophageal cancer as shown in Head and Neck cancer and cervical cancer. Whole exome sequencing (WES) was performed to explore the mutational landscape and potential molecular signature of HPV positive versus HPV negative EAC, which includes four hr-HPV-positive and 8 HPV-negative treatment naive fresh-frozen EAC tissue specimens and matched normal tissues.","abstract":"High-risk human papillomavirus (hr-HPV) has been implicated in a subset of patients with esophageal adenocarcinoma (EAC). We therefore hypothesized that HPV associated EAC may have distinct genomic aberrations compared with viral negative esophageal cancer as shown in Head and Neck cancer and cervical cancer. Whole exome sequencing (WES) was performed to explore the mutational landscape and potential molecular signature of HPV positive versus HPV negative EAC, which includes four hr-HPV-positive and 8 HPV-negative treatment naive fresh-frozen EAC tissue specimens and matched normal tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-07-29T02:18:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001341","title":"GENOME-WIDE ASSOCIATION STUDIES IDENTIFY GENETIC LOCI FOR LOW VON WILLEBRAND FACTOR LEVELS","description":"Background. von Willebrand Factor (VWF) levels are highly variable and are largely determined by genetic factors. Low VWF levels are associated with bleeding symptoms and are a diagnostic criterion for von Willebrand Disease, the most common inherited bleeding disorder. To date, it is unknown which genetic loci besides morbific variation in VWF, are associated with reduced VWF levels. Therefore, we conducted a meta-analysis of genome-wide association studies to identify genetic loci associated with low VWF levels.  Methods and results. For this meta-analysis we included 31,149 participants of European ancestry from eleven community-based studies. From all participants VWF antigen (VWF:Ag) measurements and genome-wide single nucleotide polymorphisms (SNPs) scans were available. Each study conducted analyses of all directly genotyped and imputed SNPs using logistic regression on dichotomized VWF:Ag measures (lowest 5% for blood group O and non-O) with an additive genetic model adjusted for age and sex. An inverse-variance weighted meta-analysis was performed for VWF:Ag levels and summary p-values and β-coefficients were calculated.  A total of 86 SNPs exceeded the genome-wide significance threshold of 510-8 and comprised five loci on four different chromosomes: 6q24 (smallest p-value 8.810-10), 9q34 (2.110-60), 12p13 (8.310-22), 12q23 (4.310-8), 13q13 (2.610-8). All loci were within or close to genes, including STXBP5 (6q24), STAB5 (12q23), ABO (9q34), VWF (12p13), and UFM1 (13q13).  Conclusions. In addition to ABO blood group and VWF, three other genetic loci (STXBP5, STAB2, and UFM1) are associated with low VWF levels. These findings point to novel mechanisms for the occurrence of low VWF levels.","abstract":"Background. von Willebrand Factor (VWF) levels are highly variable and are largely determined by genetic factors. Low VWF levels are associated with bleeding symptoms and are a diagnostic criterion for von Willebrand Disease, the most common inherited bleeding disorder. To date, it is unknown which genetic loci besides morbific variation in VWF, are associated with reduced VWF levels. Therefore, we conducted a meta-analysis of genome-wide association studies to identify genetic loci associated with low VWF levels.  Methods and results. For this meta-analysis we included 31,149 participants of European ancestry from eleven community-based studies. From all participants VWF antigen (VWF:Ag) measurements and genome-wide single nucleotide polymorphisms (SNPs) scans were available. Each study conducted analyses of all directly genotyped and imputed SNPs using logistic regression on dichotomized VWF:Ag measures (lowest 5% for blood group O and non-O) with an additive genetic model adjusted for age and sex. An inverse-variance weighted meta-analysis was performed for VWF:Ag levels and summary p-values and β-coefficients were calculated.  A total of 86 SNPs exceeded the genome-wide significance threshold of 510-8 and comprised five loci on four different chromosomes: 6q24 (smallest p-value 8.810-10), 9q34 (2.110-60), 12p13 (8.310-22), 12q23 (4.310-8), 13q13 (2.610-8). All loci were within or close to genes, including STXBP5 (6q24), STAB5 (12q23), ABO (9q34), VWF (12p13), and UFM1 (13q13).  Conclusions. In addition to ABO blood group and VWF, three other genetic loci (STXBP5, STAB2, and UFM1) are associated with low VWF levels. These findings point to novel mechanisms for the occurrence of low VWF levels.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001342","title":"HCC_organoid_study","description":"HCC derived liver organoids are assessed for reproducing in vitro the pathofysiology. Cultures arecompared to liver donor-derived organoids (non-cancer). By sequencing sequencing of a set of 500 cancer genes, we will assess whether the cultured cells faithfully represent the genetic spectra of livertumours.","abstract":"Targeted sequencing of 500 cancer genes in HCC derived liver organoids and healthy donor-derived organoids.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001343","title":"Somatic_Genetics_of_lesions_from_a_POT1_patient","description":"In this project we will use exome sequencing to identify somatic mutations in lesions from a patient with a germline mutation in the protection of telomeres 1 gene (POT1).","abstract":"POT1 is a factor that regulates telomere length and also participates in telomere capping. We have previously found that germline mutations in POT1 that disrupt telomere binding predispose to melanoma development. In this project we will use exome sequencing to identify somatic mutations in lesions from a patient with a germline mutation in the protection of telomeres 1 gene (POT1).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-07-30T11:07:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001344","title":"Thu_Jul_30_14:29:18_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001345","title":"Thu_Jul_30_14:56:20_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001346","title":"Thu_Jul_30_15:25:49_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001347","title":"Fri_Jul_31_11:30:46_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001348","title":"Melanoma_multi_site_metastases","description":"Despite multiple large-scale sequencing studies offering substantial insight into the genomic landscape of cutaneous melanoma, the molecular events surrounding disease progression and the resulting molecular heterogeneity between metastases have not been fully elucidated. We have been applying whole genome and transcriptome sequencing across metastases collected during post mortem as well as to multi-site metastases during treatment","abstract":"Cancer immunotherapies have demonstrated profound tumour regressions in patients with metastatic cancer. However only about 25% of patients treated with an immune checkpoint inhibitor respond, resulting in high levels of morbidity and costly treatment failures.  Patients differ in their immune response and efficacious immunotherapy requires personalisation of treatment. There are currently no validated and clinically qualified biomarkers for the enrichment of likely responders to immunotherapy. We aim to identify genomic insights into this problem and evaluate their function within the host immune response. We will analyse this data in the context of recent research in this field and critically evaluate the feasibility of identifying a molecular marker of durable response to anti-CTLA4 immunotherapy. We hope this will help inform further translational research in this field.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-07-31T13:51:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001349","title":"Mesothelioma_H2731_ENU_resistance_to_TRAIL__","description":"This study involves mutagenizing H2731, a mesothelioma cell line, with ENU to identify those mutations which engender resistance to a targeted treatment.","abstract":"In the last decade we have begun to move towards the use of targeted therapeutics in the clinic, often resulting in dramatic response rates in cancer patients. However, clinical experience has demonstrated time and time again that such responses are invariably followed by the development of drug resistance. Identification of the underlying mechanisms may enable us to reverse such resistance. Traditional methods of modelling this resistance in vitro can lead to a plethora of potential resistance mechanisms that can be difficult to decipher.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001350","title":"Fri_Jul_31_16:47:25_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001351","title":"Mon_Aug_03_09:25:07_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001352","title":"Mon_Aug_03_09:26:01_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001353","title":"Independent development of lymphoid and histiocytic malignancies from a shared early precursor","description":"Recent reports have described lineage flexibility in patients with recurrent hematologic malignancies. We encountered a boy with T-lineage acute lymphoblastic leukemia, non-Langerhans cell histiocytosis and histiocytic sarcoma. All tumors showed identical T-cell receptor rearrangements, but SNP arrays and whole exome sequencing revealed unique aberrations in each tumor. From the genetic data we conclude that the tumors were derived from a precursor cell with lineage plasticity for both lymphoid and myeloid development. From this precursor cell, the tumors evolved with independent genetic progression in a non-linear manner.","abstract":"Recent reports have described lineage flexibility in patients with recurrent hematologic malignancies. We encountered a boy with T-lineage acute lymphoblastic leukemia, non-Langerhans cell histiocytosis and histiocytic sarcoma. All tumors showed identical T-cell receptor rearrangements, but SNP arrays and whole exome sequencing revealed unique aberrations in each tumor. From the genetic data we conclude that the tumors were derived from a precursor cell with lineage plasticity for both lymphoid and myeloid development. From this precursor cell, the tumors evolved with independent genetic progression in a non-linear manner.","study_type":"Other","pubmed_ids":[26202925],"external_links":null,"is_released":true,"released_date":"2015-08-03T10:42:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001354","title":"Genome-wide association data on male-pattern baldness","description":"The study comprises 1000Genomes imputed data for 581 MPB cases and 416 male controls. Cases are selected for age&lt;40 and Hamilton-Norwood grade V-VII. Control include 270 males &gt;60 years no signs of AGA (Hamilton-Norwood grade I).","abstract":"The study comprises 1000Genomes imputed data for 581 MPB cases and 416 male controls. Cases are selected for age&lt;40 and Hamilton-Norwood grade V-VII. Control include 270 males &gt;60 years no signs of AGA (Hamilton-Norwood grade I).","study_type":"Other","pubmed_ids":[18849994,22032556,22693459,23358095,23701444],"external_links":null,"is_released":true,"released_date":"2015-08-03T13:26:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001355","title":"Whole_Genome_Sequencing_of_INTERVAL","description":"Whole genome sequencing of participants from the INTERVAL study.","abstract":"INTERVAL is a randomised controlled trial in up to 50,000 blood donors being conducted within the framework of the UK’s National Blood and Transplant service (NHSBT). The main objectives are to determine whether blood can be safely collected more frequently than present practice, and whether donation intervals can be tailored to the individual’s capacity to give blood. Added value is provided by this study’s creation of a national epidemiological bio-resource that will contribute to broader public health research. Here we propose to whole genome sequence a subset of participants from the INTERVAL cohort. (http://www.intervalstudy.org.uk/)","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-08-03T16:28:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001356","title":"Mon_Aug_03_16:29:25_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001357","title":"Tue_Aug_04_11:13:41_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001358","title":"Tue_Aug_04_12:49:37_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001359","title":"Tue_Aug_04_12:54:45_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001360","title":"Tue_Aug_04_14:39:00_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001361","title":"Tue_Aug_04_15:48:55_BST_2015_EBI, submitted by PROD","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001363","title":"Tue_Aug_04_15:50:45_BST_2015_EBI, submitted by PROD","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001365","title":"Tue_Aug_04_16:31:03_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001366","title":"Tue_Aug_04_16:35:55_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001367","title":"Tue_Aug_04_16:38:20_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001368","title":"Tue_Aug_04_16:41:38_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001369","title":"Tue_Aug_04_16:41:43_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001370","title":"Mesothelioma_H2804_ENU_resistance_to_TRAIL__","description":"This study involves mutagenizing H2804, a mesothelioma cell line, with ENU to identify those mutations which engender resistance to a targeted treatment.","abstract":"In the last decade we have begun to move towards the use of targeted therapeutics in the clinic, often resulting in dramatic response rates in cancer patients. However, clinical experience has demonstrated time and time again that such responses are invariably followed by the development of drug resistance. Identification of the underlying mechanisms may enable us to reverse such resistance. Traditional methods of modelling this resistance in vitro can lead to a plethora of potential resistance mechanisms that can be difficult to decipher.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001371","title":"Thu_Aug_06_10_38_29_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001372","title":"Thu_Aug_06_11_53_23_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001373","title":"Thu_Aug_06_11_55_29_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001374","title":"Thu_Aug_06_12_01_00_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001375","title":"Thu_Aug_06_12_08_43_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001376","title":"Thu_Aug_06_12_15_12_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001377","title":"Thu_Aug_06_12_18_37_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001378","title":"Thu_Aug_06_12_19_25_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001379","title":"Thu_Aug_06_12_19_30_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001380","title":"Thu_Aug_06_12_21_22_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001381","title":"Thu_Aug_06_12_21_26_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001382","title":"OCCAMS_Oesophageal_Cancer_Organoids_1","description":"***THIS DATA CAN ONLY BE USED FOR NON-COMMERCIAL CANCER RESEARCH*** Sequencing of organoid cell lines derived from oesophageal tumour sections taken from patients diagnosed with primary oesophageal cancer who underwent tumour resection surgery.","abstract":"ONLY BE USED FOR NON-COMMERCIAL CANCER RESEARCH*** Sequencing of organoid cell lines derived from oesophageal tumour sections taken from patients diagnosed with primary oesophageal cancer who underwent tumour resection surgery.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-08-06T13:15:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001383","title":"Thu_Aug_06_13_48_01_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001384","title":"Thu_Aug_06_13_48_05_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001385","title":"A somatic reference standard for cancer genome sequencing with COLO829","description":"Identification of somatic alterations in cancer has become feasible with the massive adoption of next generation sequencing. However, due to variability in sequencing and informatics pipelines, a common somatic reference is needed. We thus performed paired whole genome sequencing of a metastatic melanoma cell line (COLO829) and a matched lymphoblastoid line (COLO829BL) across three institutions (TGen, Illumina, Genome Sciences Centre at the British Columbia Cancer Agency). We performed a meta-analysis of all data, in combination with the originally reported analysis of these cell lines by Pleasance et al (PMID: 20016485), and report a somatic reference standard based on consensus events. DNA extractions, library preparation, sequencing, and analysis were separately performed at each site. Results were compiled with sequence data previously generated for the cell lines to identify true positive variants, collectively representing a somatic reference standard. Overall, common somatic events include point mutations, small insertion/deletions, and genes affected by concurrent copy number changes. We additionally show divergence of somatic mutations in COLO829 associated with differences in cell line lineage. We present this reference to the community as a standard for enabling interpretation and identification of somatic mutations across institutions and analytical pipelines.","abstract":"Identification of somatic alterations in cancer has become feasible with the massive adoption of next generation sequencing. However, due to variability in sequencing and informatics pipelines, a common somatic reference is needed. We thus performed paired whole genome sequencing of a metastatic melanoma cell line (COLO829) and a matched lymphoblastoid line (COLO829BL) across three institutions (TGen, Illumina, Genome Sciences Centre at the British Columbia Cancer Agency). We performed a meta-analysis of all data, in combination with the originally reported analysis of these cell lines by Pleasance et al (PMID: 20016485), and report a somatic reference standard based on consensus events. DNA extractions, library preparation, sequencing, and analysis were separately performed at each site. Results were compiled with sequence data previously generated for the cell lines to identify true positive variants, collectively representing a somatic reference standard. Overall, common somatic events include point mutations, small insertion/deletions, and genes affected by concurrent copy number changes. We additionally show divergence of somatic mutations in COLO829 associated with differences in cell line lineage. We present this reference to the community as a standard for enabling interpretation and identification of somatic mutations across institutions and analytical pipelines.","study_type":"Other","pubmed_ids":[27094764],"external_links":null,"is_released":true,"released_date":"2015-08-06T21:38:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001386","title":"Novel genes for Intellectual Disability identified using whole genome sequence and pathway analysis","description":"Intellectual Disability (ID) is one of the most common global disorders. However for ~30% of patients with ID no cause is identified, despite a clinical diagnostic odyssey that includes genome wide clinical microarray (CMA). We carefully selected 8 trios, each composed of a child with ID and brain structural defect, and both normal parents for whole genome sequencing (WGS). We conducted WGS on the trio and filtered out de novo single nucleotide variants (SNVs) and then used a pathway-based refinement to select candidates. We confirmed a de novo pathogenic SNV in ARID1B, and likely pathogenic SNVs in CACNB3, SPRY4, PHF6, SQSTM1 and UPF1 in 5 of the 8 children. All genes except ARID1B and PHF6 are previously unreported for ID. We analysed our WGS data using 4 independent algorthims for copy number and structural variation including using de novo whole genome assembly. We confirmed one likely contributory 165kb de novo CNV (missed by CMA). We conducted a validation study of over 2000 exomes for our novel candidate genes and also present a strategy to analyze the non-coding sequence space. This study provides an extensive analysis of WGS in the context of ID and yielded causative variants in &gt;60% of cases.","abstract":"Intellectual Disability (ID) is one of the most common global disorders. However for ~30% of patients with ID no cause is identified, despite a clinical diagnostic odyssey that includes genome wide clinical microarray (CMA). We carefully selected 8 trios, each composed of a child with ID and brain structural defect, and both normal parents for whole genome sequencing (WGS). We conducted WGS on the trio and filtered out de novo single nucleotide variants (SNVs) and then used a pathway-based refinement to select candidates. We confirmed a de novo pathogenic SNV in ARID1B, and likely pathogenic SNVs in CACNB3, SPRY4, PHF6, SQSTM1 and UPF1 in 5 of the 8 children. All genes except ARID1B and PHF6 are previously unreported for ID. We analysed our WGS data using 4 independent algorthims for copy number and structural variation including using de novo whole genome assembly. We confirmed one likely contributory 165kb de novo CNV (missed by CMA). We conducted a validation study of over 2000 exomes for our novel candidate genes and also present a strategy to analyze the non-coding sequence space. This study provides an extensive analysis of WGS in the context of ID and yielded causative variants in &gt;60% of cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-08-06T23:01:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001387","title":"Genomes of Relapsing Neuroblastoma","description":"Neuroblastoma is a malignancy of the developing sympathetic nervous system that is often lethal when relapse occurs, but the molecular mechanisms behind this process are poorly defined. We here used whole-exome sequencing, mRNA expression, array CGH and DNA methylation analysis to holistically characterize 16 paired samples from neuroblastoma patients at diagnosis and relapse. The mutational burden significantly increased in relapsing tumors accompanied by altered mutational signatures and reduced subclonal heterogeneity. Global allele frequencies at relapse indicated clonal mutation selection during disease progression. Promoter methylation patterns were consistent over disease course and patient-specific. Recurrent alterations at relapse included mutations in the putative CHD5 neuroblastoma tumor suppressor, chromosome 9p losses, DOCK8 mutations, inactivating mutations in PTPN14 and a relapse-specific activity pattern for the PTPN14 target gene, YAP. Recurrent new mutations in HRAS, KRAS, DOCK8 and genes mediating cell-cell interaction in 13/16 relapse tumors also indicate disturbances in signaling pathways mediating mesenchymal transition. Our data shed first light on genetic alteration frequency, identity and evolution in neuroblastoma.","abstract":"Neuroblastoma is a malignancy of the developing sympathetic nervous system that is often lethal when relapse occurs, but the molecular mechanisms behind this process are poorly defined. We here used whole-exome sequencing, mRNA expression, array CGH and DNA methylation analysis to holistically characterize 16 paired samples from neuroblastoma patients at diagnosis and relapse. The mutational burden significantly increased in relapsing tumors accompanied by altered mutational signatures and reduced subclonal heterogeneity. Global allele frequencies at relapse indicated clonal mutation selection during disease progression. Promoter methylation patterns were consistent over disease course and patient-specific. Recurrent alterations at relapse included mutations in the putative CHD5 neuroblastoma tumor suppressor, chromosome 9p losses, DOCK8 mutations, inactivating mutations in PTPN14 and a relapse-specific activity pattern for the PTPN14 target gene, YAP. Recurrent new mutations in HRAS, KRAS, DOCK8 and genes mediating cell-cell interaction in 13/16 relapse tumors also indicate disturbances in signaling pathways mediating mesenchymal transition. Our data shed first light on genetic alteration frequency, identity and evolution in neuroblastoma.","study_type":"Other","pubmed_ids":[26121086],"external_links":null,"is_released":true,"released_date":"2015-08-10T10:25:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001388","title":"Mon_Aug_10_14_15_59_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001389","title":"Mon_Aug_10_14_16_03_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001390","title":"Mon_Aug_10_14_18_33_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001391","title":"Mon_Aug_10_14_18_51_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001392","title":"Mon_Aug_10_14_18_54_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001393","title":"Whole Exome Sequencing of BM/CD34+ cells and corresponding mesenchymal stromal cells from patients with myelodysplastic syndromes","description":"Whole Exome Sequencing of BM/CD34+ cells and corresponding mesenchymal stromal cells from patients with myelodysplastic syndromes.","abstract":"Whole Exome Sequencing of BM/CD34+ cells and corresponding mesenchymal stromal cells from patients with myelodysplastic syndromes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001394","title":"Genome-wide identification of distinct miRNA-mRNA target regulation pairs in Non-Hodgkin lymphomas: a report from the ICGC MMML-Seq consortium","description":"We obtained miRNA profiles by miRnome sequencing from ICGC MMML-Seq patients diagnosed with Burkitt lymphoma, diffuse large B-cell lymphoma and follicular lymphoma and provide evidence of subtype-specific miRNA expression differences. We describe differentially expressed, mutated, edited and not previously annotated miRNAs.\nAddditionally, by performing argonaute-2 photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation (PAR-CLIP) experiments, we obtained a set of biochemically-validated miRNA binding sites and  identified miRNA-mRNA interaction pairs with a negative correlation in patient RNASeq data.","abstract":"We obtained miRNA profiles by miRnome sequencing from ICGC MMML-Seq patients diagnosed with Burkitt lymphoma, diffuse large B-cell lymphoma and follicular lymphoma and provide evidence of subtype-specific miRNA expression differences. We describe differentially expressed, mutated, edited and not previously annotated miRNAs.\nAddditionally, by performing argonaute-2 photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation (PAR-CLIP) experiments, we obtained a set of biochemically-validated miRNA binding sites and  identified miRNA-mRNA interaction pairs with a negative correlation in patient RNASeq data.","study_type":"Other","pubmed_ids":[27390358],"external_links":null,"is_released":true,"released_date":"2015-08-13T07:31:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001395","title":"Mon_Aug_10_14_51_19_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001396","title":"Genome_Diversity_in_Africa_Project___GemCode_libraries_","description":"High depth whole genome sequencing  from GemCode (10x Genomics) DNA libraries containing long range linkage information for two African samples (1 Zulu, South Africa, and 1 Ashanti, Ghana).This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Given the central importance of Africa to studies of human origins, genetic diversity and disease susceptibility, large-scale and representative characterisation of genetic diversity in Africa is needed. One of the biggest challenges in reconstructing genomes from short read data is the limited phasing information. The use of DNA libraries containing long range linkage information could present a significant advantage. These high coverage data have been generated for two African samples (1 Zulu, South Africa, and 1 Ashanti, Ghana) from GemCode (10x Genomics) DNA libraries containing long range linkage information.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001397","title":"Fri_Aug_14_11_40_03_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001398","title":"Fri_Aug_14_11_40_41_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001399","title":"Fri_Aug_14_11_40_46_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001400","title":"Fri_Aug_14_16_10_38_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001401","title":"Fri_Aug_14_16_11_18_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001402","title":"Fri_Aug_14_16_11_23_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001403","title":"Tue_Aug_18_10_09_18_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001404","title":"Tue_Aug_18_10_09_55_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001405","title":"Tue_Aug_18_10_09_59_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001406","title":"Tue_Aug_18_10_13_12_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001407","title":"Tue_Aug_18_10_13_47_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001408","title":"Tue_Aug_18_10_13_52_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001409","title":"Tue_Aug_18_10_14_52_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001410","title":"Tue_Aug_18_10_20_55_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001411","title":"Tue_Aug_18_10_22_06_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001412","title":"Tue_Aug_18_10_22_11_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001413","title":"Tue_Aug_18_10_24_15_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001414","title":"Tue_Aug_18_10_26_47_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001415","title":"Tue_Aug_18_10_26_51_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001416","title":"Tue_Aug_18_10_27_37_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001417","title":"Tue_Aug_18_10_30_23_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001418","title":"Exome Sequencing to Define the Landscape of Plasma Cells in Systemic Light chain Amyloidosis","description":"Systemic light chain amyloidosis (AL) is characterized by the deposition of immunoglobulin light chains as amyloid fibrils in different organs, where they form toxic protein aggregates. The underlying disease is a plasma cell disorder, but limited whole exome data are available. We report the findings of an exome sequencing study in AL to define a plasma cell signature and compare this to monoclonal gammopathy of undefined significance (MGUS) and myeloma (MM). \nTwenty-four samples from unselected newly diagnosed untreated AL patients were analysed. CD138+ cells were isolated from bone marrow cells using MACSorting (Miltenyi Biotech, Bisley, UK). Cells were lysed in RLT+ buffer and DNA/RNA extracted using the AllPrep kit (Qiagen, Manchester, UK). Peripheral blood was isolated from patients, white blood cells purified by Ficoll-Pacque and DNA extracted using the QIAamp DNA mini kit (Qiagen). \nThere were a median of 47 acquired nonsynonymous variants (range 4-253) per patient. Thirty percent of patients yielded a mutation in a myeloma driver gene. These mutations were either clonal or sub-clonal. There was evidence of MAPK activation with NRAS mutations, NF-κB activation and DNA repair pathway alterations. Exome data were used to determine the cytogenetic groups of AL samples and identified hyperdiploidy in 33% of cases and t(11;14) in 33% of cases. All translocations were generated via class switch recombination and breakpoints on chromosome 11 fell into the expected regions. A novel translocation, unlikely to be driving disease progression was identified involving RCC1. Finally, further analysis of the APCS gene encoding for the SAP protein did not show any biased genotype in the AL population in comparison to the general population. We conclude that exome sequencing identifies a genetic make-up of AL that is similar to other plasma cell disorders such as MM and MGUS. This not only includes copy number abnormalities and translocations but also nonsynonymous mutations.","abstract":"Systemic light chain amyloidosis (AL) is characterized by the deposition of immunoglobulin light chains as amyloid fibrils in different organs, where they form toxic protein aggregates. The underlying disease is a plasma cell disorder, but limited whole exome data are available. We report the findings of an exome sequencing study in AL to define a plasma cell signature and compare this to monoclonal gammopathy of undefined significance (MGUS) and myeloma (MM). \nTwenty-four samples from unselected newly diagnosed untreated AL patients were analysed. CD138+ cells were isolated from bone marrow cells using MACSorting (Miltenyi Biotech, Bisley, UK). Cells were lysed in RLT+ buffer and DNA/RNA extracted using the AllPrep kit (Qiagen, Manchester, UK). Peripheral blood was isolated from patients, white blood cells purified by Ficoll-Pacque and DNA extracted using the QIAamp DNA mini kit (Qiagen). \nThere were a median of 47 acquired nonsynonymous variants (range 4-253) per patient. Thirty percent of patients yielded a mutation in a myeloma driver gene. These mutations were either clonal or sub-clonal. There was evidence of MAPK activation with NRAS mutations, NF-κB activation and DNA repair pathway alterations. Exome data were used to determine the cytogenetic groups of AL samples and identified hyperdiploidy in 33% of cases and t(11;14) in 33% of cases. All translocations were generated via class switch recombination and breakpoints on chromosome 11 fell into the expected regions. A novel translocation, unlikely to be driving disease progression was identified involving RCC1. Finally, further analysis of the APCS gene encoding for the SAP protein did not show any biased genotype in the AL population in comparison to the general population. We conclude that exome sequencing identifies a genetic make-up of AL that is similar to other plasma cell disorders such as MM and MGUS. This not only includes copy number abnormalities and translocations but also nonsynonymous mutations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-08-19T12:34:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001419","title":"Wed_Aug_19_13_13_05_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001420","title":"Wed_Aug_19_13_13_40_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001421","title":"Wed_Aug_19_13_13_44_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001422","title":"Precursor_lesions__clonal_architecture_and_relapse_in_Wilms_nephroblastoma","description":"Targeted resequencing at high depth (21 genes, 9 chromosomal regions): at least 4 FFPE samples per case and matched germline DNA: •100 cases with detailed outcome data, including 15 cases with tumour relapse (515 samples)•40 cases with matched pre-chemotherapy biopsies (240 samples)•50 nephrogenic rests matched to above cases (50 samples)We expect a proportion (possibly 10%) of cases to be mutationally silent on the above studies, and propose to subsequently carry out integrated whole-genome, methylome and transcriptome studies on matched frozen tissue from these cases","abstract":"Wilms' nephroblastoma affects 1 in 10,000 children and is the commonest paediatric kidney malignancy and second commonest abdominal solid malignancy of childhood. More than 85% of patients achieve long-term survival but, in approximately half of patients, treatment involves doxorubicin or more intensive chemotherapy and/or radiotherapy and is associated with significant long-term complications, especially heart failure and second malignancies. We need more precise methods for identifying those patients in whom intensive treatment can be safely reduced and/or replaced by newer targeted agents. A subset of patients who are not initially assigned to a high-risk category relapse unpredictably, and almost half of these patients then face a poor prognosis, despite intensive treatment. Screening for relapse is currently based on  specialist radiology, which often involves the child and carer(s) travelling  considerable distances to a specialist centre. An alternative blood test for circulating tumour DNA would be much easier to access.There are few validated genetic biomarkers: loss of chromosomes 1p and 16q, gain of 1q, and TP53 mutations in anaplastic tumours are all associated with an increased risk of relapse, but all found in a minority of cases who relapse. Previous genetic studies and emerging exome sequencing data identified recurrent point mutations and small indels in 21 genes and 9 recurrent chromosomal structural variants. The majority of these variants have not been studied in sufficient numbers to test their association with outcome. We have also found that known prognostic markers are not detectable uniformly throughout the tumour because of intra-tumour heterogeneity, raising questions about the number of tumour samples needed for reliable detection in clinical practice.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-08-20T14:08:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001423","title":"Thu_Aug_20_16_57_17_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001424","title":"Thu_Aug_20_16_57_57_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001425","title":"Thu_Aug_20_16_58_02_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001426","title":"Whole-exome sequencing of primary central nervous system lymphoma","description":"In the current study, to delineate a comprehensive registry of gene mutations in PCNSL, we performed combined whole exome sequencing of 35 PCNSL samples.","abstract":"In the current study, to delineate a comprehensive registry of gene mutations in PCNSL, we performed combined whole exome sequencing of 35 PCNSL samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001427","title":"Trans-ethnic genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation","description":"We carried out a trans-ethnic genome-wide association and replication study of blood pressure phenotypes amongst up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 novel loci to be associated with blood pressure (P=3.9x10-11 to P=5.0x10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that at some of the loci identified DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 novel loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7, TBX2) function. The novel and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, cardiovascular and all-cause mortality (P=0.04 to 8.6x10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.","abstract":"We carried out a trans-ethnic genome-wide association and replication study of blood pressure phenotypes amongst up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 novel loci to be associated with blood pressure (P=3.9x10-11 to P=5.0x10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that at some of the loci identified DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 novel loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7, TBX2) function. The novel and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, cardiovascular and all-cause mortality (P=0.04 to 8.6x10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-08-25T03:40:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001428","title":"second study","description":"second study","abstract":"second study","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001429","title":"Congenital_anosmia_2","description":"Congenital anosmias can be complete (the lack of a sense of smell) or specific (the inability to detect specific smells). Here we obtained genomic DNA from families with multiple individuals with anosmia, suggesting they are congenital. These include those inherited in a manner consistent with dominant and recessive alleles. We have sequenced the exomes of both affected and unaffected family members on the Illumina platform.","abstract":"Here we sequence the exomes of 14 individuals with complete or specific anosmias, plus 10 unaffected controls from the same families, on the Illumina Hiseq platform.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-08-26T13:04:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001430","title":"Investigation of transcriptomes in long-lived individuals.","description":"Human longevity is a complex phenotype influenced by both genetic and environmental components, while the genetic contribution is estimated between 15-30%. Interestingly, genetic approaches have resulted so far in only very few confirmed longevity associations. This observation emphasizes that mechanisms beyond genetics, such as environmental factors, play a fundamental role in this phenotype. To address both genetic and non-genetic factors, we conducted a large-scale RNA-seq-based expression quantitative trait loci (eQTL) study with a subsequent heritability analysis. The study was performed on peripheral blood samples obtained from 244 individuals, collected by a Danish-German consortium, of which 57 were at least 90 years old.","abstract":"Human longevity is a complex phenotype influenced by both genetic and environmental components, while the genetic contribution is estimated between 15-30%. Interestingly, genetic approaches have resulted so far in only very few confirmed longevity associations. This observation emphasizes that mechanisms beyond genetics, such as environmental factors, play a fundamental role in this phenotype. To address both genetic and non-genetic factors, we conducted a large-scale RNA-seq-based expression quantitative trait loci (eQTL) study with a subsequent heritability analysis. The study was performed on peripheral blood samples obtained from 244 individuals, collected by a Danish-German consortium, of which 57 were at least 90 years old.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001431","title":"Breast Cancer - Subtype defined by an amplification of the HER2 gene","description":"Clinically positive HER2 (cHER2+) breast cancers (BC) are defined by the amplification and overexpression of the human epidermal growth factor receptor (HER2/ERBB2) gene on chromosome region 17q12 and represent 15% of all BCs. Although anti-HER2 targeted therapies have improved BC’s natural history, the magnitude of their benefit varies widely between patients and deciphering the genomic heterogeneity of cHER2+ BC may provide a basis to better understand patients’ outcome. As part of the ICGC Breast Cancer Working Group effort, we combined whole genome sequencing and transcriptomic analyses of 64 cHER2+ primary invasive carcinomas.","abstract":"Clinically positive HER2 (cHER2+) breast cancers (BC) are defined by the amplification and overexpression of the human epidermal growth factor receptor (HER2/ERBB2) gene on chromosome region 17q12 and represent 15% of all BCs. Although anti-HER2 targeted therapies have improved BC’s natural history, the magnitude of their benefit varies widely between patients and deciphering the genomic heterogeneity of cHER2+ BC may provide a basis to better understand patients’ outcome. As part of the ICGC Breast Cancer Working Group effort, we combined whole genome sequencing and transcriptomic analyses of 64 cHER2+ primary invasive carcinomas.","study_type":"Other","pubmed_ids":[27406316],"external_links":null,"is_released":true,"released_date":"2015-08-28T09:47:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001432","title":"Exome sequencing of a Rosette-forming glioneuronal tumor arising in the spinal cord","description":"Rosette-forming glioneuronal tumour (RGNT) of the IV ventricle is a very recent entity, recognized in the latest WHO classification of Central Nervous System Tumors 1. Until 2007, RGNT was diagnosed as neuroepithelial disembryoplastic tumor 2. RGNT is composed by two distinct features: a glial component, with typical characteristics of pilocytic astrocytoma, and a component forming neurocytic rosettes, with eosinophilic regions positive for synaptophysin and/or perivascular rosettes. This rare tumor affects predominantly adult females (61%), with mean age around 32 years, typically originating in the fourth ventricle and/or aqueduct 1,3. Due to its usual indolent course it is considered a WHO grade I tumor 1. Hitherto, less than 100 cases are reported in the literature 4, most of them as case reports of MRI, histopathological and immunohistochemical findings 5-17. There are few molecular studies, with the only recurrent genetic alterations identified being PIK3CA 18-25 or FGFR1 mutations 26. Herein, we describe a 33-year-old man with RGNT arising in a peculiar location, namely the spinal cord. We further performed an extensive immunohistochemistry and molecular analysis, using array-CGH (aCGH), whole exome and cancer-related hotspot sequencing, in order to better understand its underlying biology.","abstract":"Rosette-forming glioneuronal tumour (RGNT) of the IV ventricle is a very recent entity, recognized in the latest WHO classification of Central Nervous System Tumors 1. Until 2007, RGNT was diagnosed as neuroepithelial disembryoplastic tumor 2. RGNT is composed by two distinct features: a glial component, with typical characteristics of pilocytic astrocytoma, and a component forming neurocytic rosettes, with eosinophilic regions positive for synaptophysin and/or perivascular rosettes. This rare tumor affects predominantly adult females (61%), with mean age around 32 years, typically originating in the fourth ventricle and/or aqueduct 1,3. Due to its usual indolent course it is considered a WHO grade I tumor 1. Hitherto, less than 100 cases are reported in the literature 4, most of them as case reports of MRI, histopathological and immunohistochemical findings 5-17. There are few molecular studies, with the only recurrent genetic alterations identified being PIK3CA 18-25 or FGFR1 mutations 26. Herein, we describe a 33-year-old man with RGNT arising in a peculiar location, namely the spinal cord. We further performed an extensive immunohistochemistry and molecular analysis, using array-CGH (aCGH), whole exome and cancer-related hotspot sequencing, in order to better understand its underlying biology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001433","title":"Fixative optimisation study for BRITROC project","description":"The British Translational Research Ovarian Cancer Collaborative (BriTROC), spanning more than 10 centres across UK, is a prospective observational project focused on relapsed high-grade serous ovarian cancer (HGSOC). The first study, as a part of the project, is the Fixative optimisation study, which analyses the utility for next-generation sequencing of UMFIX samples compared to NBF-fixed and fresh frozen samples. Various DNA and sequencing quality analyses were performed to compare fixation methods in bulk tumour and biopsy samples.","abstract":"The British Translational Research Ovarian Cancer Collaborative (BriTROC), spanning more than 10 centres across UK, is a prospective observational project focused on relapsed high-grade serous ovarian cancer (HGSOC). The first study, as a part of the project, is the Fixative optimisation study, which analyses the utility for next-generation sequencing of UMFIX samples compared to NBF-fixed and fresh frozen samples. Various DNA and sequencing quality analyses were performed to compare fixation methods in bulk tumour and biopsy samples.","study_type":"Other","pubmed_ids":[26681675],"external_links":null,"is_released":true,"released_date":"2015-08-28T17:01:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001434","title":"Gene-drug association screening for glioblastoma precision oncology","description":"Glioblastomas (GBMs) are genomically heterogeneous and the most lethal type of adult brain tumor. A GBM library annotated with genomic information and drug response profiles may facilitate identification of therapeutic options. Towards this goal, we established 57 GBM patient-derived tumor cells and determined whether the specific genetic aberrations correlated with sensitivities to 60 cancer drugs. We found 36 statistically significant gene-drug response associations, including previously unrecognized linkage between EGFRvIII and ibrutinib. A GBM patient-specific gene- drug sensitivity screen identified that afatinib was one of the most effective drugs against this specific tumor, and the tumor exhibited a remarkable clinical response. Together, these data demonstrate the potential of rapid drug screening combined with genomic profiling for precision oncological treatment of GBM patients.","abstract":"Glioblastomas (GBMs) are genomically heterogeneous and the most lethal type of adult brain tumor. A GBM library annotated with genomic information and drug response profiles may facilitate identification of therapeutic options. Towards this goal, we established 57 GBM patient-derived tumor cells and determined whether the specific genetic aberrations correlated with sensitivities to 60 cancer drugs. We found 36 statistically significant gene-drug response associations, including previously unrecognized linkage between EGFRvIII and ibrutinib. A GBM patient-specific gene- drug sensitivity screen identified that afatinib was one of the most effective drugs against this specific tumor, and the tumor exhibited a remarkable clinical response. Together, these data demonstrate the potential of rapid drug screening combined with genomic profiling for precision oncological treatment of GBM patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001435","title":"BLUEPRINT DNA methylation profiles of monocytes, T cells and B cells in type 1 diabetes-discordant monozygotic twins","description":"BLUEPRINT DNA methylation profiles of monocytes, T cells and B cells in type 1 diabetes-discordant monozygotic twins","abstract":"BLUEPRINT DNA methylation profiles of monocytes, T cells and B cells in type 1 diabetes-discordant monozygotic twins","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001436","title":"Multiregion Whole Exome sequencing of paediatric High Grade Gliomas and DIPG","description":"Paediatric High Grade Gliomas (pHGG) are defined by unique, specific and highly recurrent mutations in genes encoding histone H3 variants which mark robust subgroups with distinct age of onset, anatomical distribution, clinical outcome, histopathological and radiological features. We have used whole exome sequencing to identify the main recurrent somatic mutations occurring within pHGG including H3 histones and the coincident mutations and DNA copy number events in order to classify clinically relevant subgroups and the molecular events within them as new targets for therapy.\nAnalysis of sequenced cases revealed multiple tumour subclones, spatially and temporally co-existing in a stable manner as observed by multiple sampling strategies.","abstract":"Paediatric High Grade Gliomas (pHGG) are defined by unique, specific and highly recurrent mutations in genes encoding histone H3 variants which mark robust subgroups with distinct age of onset, anatomical distribution, clinical outcome, histopathological and radiological features. We have used whole exome sequencing to identify the main recurrent somatic mutations occurring within pHGG including H3 histones and the coincident mutations and DNA copy number events in order to classify clinically relevant subgroups and the molecular events within them as new targets for therapy.\nAnalysis of sequenced cases revealed multiple tumour subclones, spatially and temporally co-existing in a stable manner as observed by multiple sampling strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-09-01T13:08:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001437","title":"Chromatin immunoprecipitation linked to next-generation whole genome sequencing (ChIP-Seq) for H3K36me3 in paediatric high grade glioma cell lines KKNS4 and SF188 with and without a G34V mutation in H3F3A","description":"Glioblastomas of children and young adults have a median survival of only 12-15months and are clinically and biologically distinct from histologically similar cancers in older adults1. They are defined by highly specific mutations in the gene encoding the histone H3.3 variant H3F3A2, occurring either at or close to key residues marked by methylation for regulation of transcription – K27 and G34. We performed chromatin immunoprecipitation linked to next-generation whole genome sequencing (ChIP-Seq) for H3K36me3 in order to test the hypothesis that, rather than total H3K36me3, the G34V mutation may instead result in differential binding of the trimethyl mark throughout the genome. Compared with H3F3A wild-type SF188 paediatric GBM cells, H3K36me3 was found to be significantly differentially bound in KNS42 cells at 5130 distinct regions of the genome corresponding to 156 genes. Concurrent whole genome DNA sequencing demonstrated that this was not confounded by copy number alterations. The cerebral hemispheric-specific G34 mutation drives a distinct expression signature through differential genomic binding of the K36 trimethylation mark (H3K36me3). The transcriptional program induced recapitulates that of the developing forebrain, and involves numerous markers of stem cell maintenance, cell fate decisions and self-renewal. Critically, H3F3A G34 mutations cause profound upregulation of MYCN, a potent oncogene which is causative of glioblastomas when expressed in the correct developmental context. This driving aberration is selectively targetable in this patient population by inhibiting kinases responsible for stabilisation of the protein.","abstract":"Glioblastomas of children and young adults have a median survival of only 12-15months and are clinically and biologically distinct from histologically similar cancers in older adults1. They are defined by highly specific mutations in the gene encoding the histone H3.3 variant H3F3A2, occurring either at or close to key residues marked by methylation for regulation of transcription – K27 and G34. We performed chromatin immunoprecipitation linked to next-generation whole genome sequencing (ChIP-Seq) for H3K36me3 in order to test the hypothesis that, rather than total H3K36me3, the G34V mutation may instead result in differential binding of the trimethyl mark throughout the genome. Compared with H3F3A wild-type SF188 paediatric GBM cells, H3K36me3 was found to be significantly differentially bound in KNS42 cells at 5130 distinct regions of the genome corresponding to 156 genes. Concurrent whole genome DNA sequencing demonstrated that this was not confounded by copy number alterations. The cerebral hemispheric-specific G34 mutation drives a distinct expression signature through differential genomic binding of the K36 trimethylation mark (H3K36me3). The transcriptional program induced recapitulates that of the developing forebrain, and involves numerous markers of stem cell maintenance, cell fate decisions and self-renewal. Critically, H3F3A G34 mutations cause profound upregulation of MYCN, a potent oncogene which is causative of glioblastomas when expressed in the correct developmental context. This driving aberration is selectively targetable in this patient population by inhibiting kinases responsible for stabilisation of the protein.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-09-01T13:31:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001438","title":"Whole genome sequencing of paediatric high grade glioma cell lines","description":"INTRODUCTION: Chromosomal rearrangements resulting in novel fusion genes are strongly associated with cancer and numerous examples exist in both adult and childhood malignancies. Structural variants frequently result in chimeric proteins targetable by novel therapeutic approaches, an outcome desperately needed in paediatric high grade glioma (pHGG). These tumours are increasingly understood to be driven by specific mutations in the genes encoding the histone H3.3 variant (H3F3A) and the chaperones ATRX/DAXX, however to date there have been no reports of structural variation. We sought to address this by carrying out integrated analysis of whole genome and transcriptome sequencing of three pHGG cell lines. METHOD: We fully sequenced the genomes and transcriptomes of the pHGG cell lines KNS42 (H3F3A G34V, TP53 R342*), SF188 (TP53 G266E) and UW479 (TP53 R158L, DAXX S683Y) using the IlluminaHiSeq2000 platform at 37-40x (DNA) and generating 74-92 million reads (RNA), respectively. Structural variants were detected using an integration of computed copy number and BreakDancer and ChimeraScan pipelines, and validated in the reference cells by PCR/Sanger sequencing. Break-part and/or fusion FISH probes were generated for validated expressed fusion transcripts and screened on tissue microarrays containing 130 pHGG samples to look for recurrence in clinical specimens, and the functions of these fusions assessed. RESULTS: 305 DNA-level structural variants involving one gene at either end were nominated in the three pHGG cell lines, many involving genes that are co-amplified. Several genome breakpoints junctions found showed microhomology regions (1-4bp), which are characteristic of microhomology-mediated break-induced-replication (MMBIR). SF188 harboured a complex amplified sequence including the genes PDGFRA (4q12), MYC (8q24.1), CCND1 (11q13.3), MLL (11q23.3) and CDK4 (12q14.1) found to be present as an extra-chromosomal double minute. Overlay of genome with transcriptome data identified 26 expressed fusion transcripts associated with DNA-level breakpoints. These included TULP4:RPTOR (t6;17 - SF188), GORASP2:CDADC1 (t2;13 - KNS42) and AKAP6:NUBPL (t12;14 - UW479). CONCLUSIONS: Numerous expressed fusion transcripts have been identified in pHGG cells which confer dysregulation of a variety of known actionable targets in cancer-related signalling pathways. Although the prevalence of fusions in clinical pHGG is not suggestive of structural variation driving tumorigenesis in this disease, the generation of these fusions may be a complementary mechanism to pathway dysregulation (such as PI3K/mTOR). Integration with functional screening data may help to identify novel drug targets, such as the protein kinase CDADC1, knockdown of which selectively kills pHGG cells in vitro.","abstract":"INTRODUCTION: Chromosomal rearrangements resulting in novel fusion genes are strongly associated with cancer and numerous examples exist in both adult and childhood malignancies. Structural variants frequently result in chimeric proteins targetable by novel therapeutic approaches, an outcome desperately needed in paediatric high grade glioma (pHGG). These tumours are increasingly understood to be driven by specific mutations in the genes encoding the histone H3.3 variant (H3F3A) and the chaperones ATRX/DAXX, however to date there have been no reports of structural variation. We sought to address this by carrying out integrated analysis of whole genome and transcriptome sequencing of three pHGG cell lines. METHOD: We fully sequenced the genomes and transcriptomes of the pHGG cell lines KNS42 (H3F3A G34V, TP53 R342*), SF188 (TP53 G266E) and UW479 (TP53 R158L, DAXX S683Y) using the IlluminaHiSeq2000 platform at 37-40x (DNA) and generating 74-92 million reads (RNA), respectively. Structural variants were detected using an integration of computed copy number and BreakDancer and ChimeraScan pipelines, and validated in the reference cells by PCR/Sanger sequencing. Break-part and/or fusion FISH probes were generated for validated expressed fusion transcripts and screened on tissue microarrays containing 130 pHGG samples to look for recurrence in clinical specimens, and the functions of these fusions assessed. RESULTS: 305 DNA-level structural variants involving one gene at either end were nominated in the three pHGG cell lines, many involving genes that are co-amplified. Several genome breakpoints junctions found showed microhomology regions (1-4bp), which are characteristic of microhomology-mediated break-induced-replication (MMBIR). SF188 harboured a complex amplified sequence including the genes PDGFRA (4q12), MYC (8q24.1), CCND1 (11q13.3), MLL (11q23.3) and CDK4 (12q14.1) found to be present as an extra-chromosomal double minute. Overlay of genome with transcriptome data identified 26 expressed fusion transcripts associated with DNA-level breakpoints. These included TULP4:RPTOR (t6;17 - SF188), GORASP2:CDADC1 (t2;13 - KNS42) and AKAP6:NUBPL (t12;14 - UW479). CONCLUSIONS: Numerous expressed fusion transcripts have been identified in pHGG cells which confer dysregulation of a variety of known actionable targets in cancer-related signalling pathways. Although the prevalence of fusions in clinical pHGG is not suggestive of structural variation driving tumorigenesis in this disease, the generation of these fusions may be a complementary mechanism to pathway dysregulation (such as PI3K/mTOR). Integration with functional screening data may help to identify novel drug targets, such as the protein kinase CDADC1, knockdown of which selectively kills pHGG cells in vitro.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001439","title":"Tue_Sep_01_14_10_17_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001440","title":"Tue_Sep_01_14_10_54_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001441","title":"Tue_Sep_01_14_10_58_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001442","title":"Tue_Sep_01_14_12_21_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001443","title":"Tue_Sep_01_14_12_56_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001444","title":"Tue_Sep_01_14_13_00_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001445","title":"Tue_Sep_01_14_15_49_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001446","title":"Tue_Sep_01_14_16_30_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001447","title":"Tue_Sep_01_14_16_34_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001456","title":"BLUEPRINT EpiVar 450K DNA methylation profiles of naive CD4+ T-cells, monocytes & neutrophils","description":"BLUEPRINT EpiVar 450K DNA methylation profiles of naive CD4+ T-cells,\n&gt; monocytes &amp; neutrophils","abstract":"BLUEPRINT EpiVar 450K DNA methylation profiles of naive CD4+ T-cells,\n&gt; monocytes &amp; neutrophils","study_type":"Other","pubmed_ids":[27863251,28126036],"external_links":null,"is_released":true,"released_date":"2015-09-04T09:55:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001457","title":"Genetic and epigenetic characterization of adenoid cystic carcinoma","description":"Translocation events are frequent in cancer and may create chimeric fusions or regulatory rearrangements that drive oncogene overexpression. Although regulatory rearrangements are increasingly recognized in hematopoietic and even solid tumors, the underlying mechanisms remain obscure. Here we identify super-enhancer translocations that drive overexpression of the oncogenic transcription factor MYB as a unifying theme in adenoid cystic carcinoma (ACC). Whole genome sequencing data and chromatin state maps for 13 primary tumors and xenografts reveal distinct chromosomal rearrangements that juxtapose super-enhancer clusters to the MYB locus. Chromosome conformation capture confirms that the translocated enhancers physically interact with the MYB promoter. Remarkably, the MYB product itself binds to the translocated enhancers, thus creating a positive feedback loop that sustains its own expression. MYB also binds a large number of active enhancers that drive opposing regulatory programs in alternate cell lineages in ACC. MYB cooperates with the transcription factor TP63 in the myoepithelial component of the tumors, but promotes a Notch program in the luminal epithelial component. Bromodomain inhibitors, which disrupt enhancer function, slow tumor growth in ACC primagraft models in vivo, but are ineffective against high grade tumors that harbor activating mutations in the Notch pathway. Thus, our study identifies super-enhancer translocations as a unifying feature of ACC, and provides insight into the mechanism by which sustained MYB overexpression drives alternate cell fates in this disease.Processed ChIP-seq data is available on GEO under accession number GSE76465.","abstract":"Translocation events are frequent in cancer and may create chimeric fusions or regulatory rearrangements that drive oncogene overexpression. Although regulatory rearrangements are increasingly recognized in hematopoietic and even solid tumors, the underlying mechanisms remain obscure. Here we identify super-enhancer translocations that drive overexpression of the oncogenic transcription factor MYB as a unifying theme in adenoid cystic carcinoma (ACC). Whole genome sequencing data and chromatin state maps for 13 primary tumors and xenografts reveal distinct chromosomal rearrangements that juxtapose super-enhancer clusters to the MYB locus. Chromosome conformation capture confirms that the translocated enhancers physically interact with the MYB promoter. Remarkably, the MYB product itself binds to the translocated enhancers, thus creating a positive feedback loop that sustains its own expression. MYB also binds a large number of active enhancers that drive opposing regulatory programs in alternate cell lineages in ACC. MYB cooperates with the transcription factor TP63 in the myoepithelial component of the tumors, but promotes a Notch program in the luminal epithelial component. Bromodomain inhibitors, which disrupt enhancer function, slow tumor growth in ACC primagraft models in vivo, but are ineffective against high grade tumors that harbor activating mutations in the Notch pathway. Thus, our study identifies super-enhancer translocations as a unifying feature of ACC, and provides insight into the mechanism by which sustained MYB overexpression drives alternate cell fates in this disease.Processed ChIP-seq data is available on GEO under accession number GSE76465.","study_type":"Other","pubmed_ids":[26829750],"external_links":null,"is_released":true,"released_date":"2015-09-04T15:36:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001458","title":"GENETIC HISTORY OF ITALY","description":"Recent scientific literature has highlighted the relevance of population genetic studies both for disease association-mapping in admixed populations and for understanding the history of human migrations. Deeper insight into the history of Italian population is critical for understanding the peopling of Europe. Because of its crucial position at the centre of the Mediterranean basin, the Italian peninsula has experienced a complex history of colonization and migration, whose genetic signatures are still present in contemporary Italians. In this study, we investigated genomic variation in the Italian population using 2.5 million single nucleotide polymorphisms (SNPs) in a sample of more than 300 unrelated Italian subjects with well-defined geographical origins. We combined several analytical approaches to interpret genome-wide data on 1,272 individuals from European, Middle Eastern, and North African populations. We detected three major ancestral components contributing different proportions across the Italian peninsula, and signatures of continuous gene flow within Italy, which has produced remarkable genetic variability among contemporary Italians. In addition, we have extracted novel details about the Italian population’s ancestry: we identified genetic signatures of major historical events in Europe and the Mediterranean basin from the Neolithic (e.g., peopling of Sardinia) to recent times (e.g., ‘barbarian invasion’ of Northern and Central Italy). These results are valuable for further genetic, epidemiological and forensic studies in Italy and in Europe.","abstract":"Recent scientific literature has highlighted the relevance of population genetic studies both for disease association-mapping in admixed populations and for understanding the history of human migrations. Deeper insight into the history of Italian population is critical for understanding the peopling of Europe. Because of its crucial position at the centre of the Mediterranean basin, the Italian peninsula has experienced a complex history of colonization and migration, whose genetic signatures are still present in contemporary Italians. In this study, we investigated genomic variation in the Italian population using 2.5 million single nucleotide polymorphisms (SNPs) in a sample of more than 300 unrelated Italian subjects with well-defined geographical origins. We combined several analytical approaches to interpret genome-wide data on 1,272 individuals from European, Middle Eastern, and North African populations. We detected three major ancestral components contributing different proportions across the Italian peninsula, and signatures of continuous gene flow within Italy, which has produced remarkable genetic variability among contemporary Italians. In addition, we have extracted novel details about the Italian population’s ancestry: we identified genetic signatures of major historical events in Europe and the Mediterranean basin from the Neolithic (e.g., peopling of Sardinia) to recent times (e.g., ‘barbarian invasion’ of Northern and Central Italy). These results are valuable for further genetic, epidemiological and forensic studies in Italy and in Europe.","study_type":"Other","pubmed_ids":[26554880],"external_links":null,"is_released":true,"released_date":"2015-09-08T16:53:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001459","title":"GoT2D: Genetics of Type 2 Diabetes, a study of the  the genetic architecture of type 2 diabetes using low pass whole genome sequencing and high density SNP genotyping in 2,657 individuals.","description":"The Genetics of Type 2 Diabetes Consortium (GoT2D) is a collaboration between the University of Michigan, the Broad Institute and the Wellcome Trust Centre for Human Genetics. The overall aim is to extend upon recent efforts, such as genome-wide association studies (GWAS) and large scale meta-analyses. While they have proved successful at mapping genomic loci that influence human diseases, like type 2 diabetes, much of the heritability remains unexplained. In this study, we use next generation sequencing and genotyping technologies to query for lower frequency variants in the human genome. Thereby, allowing a deeper characterization of the spectrum of alleles associated with type 2 diabetes risk, and a better assessment of the genes that play a role in the etiology of type 2 diabetes development.  We studied 1,326 T2D cases and 1,331 normoglycemic controls from Northern and Central Europe (Sweden, Finland, UK, and Germany).  To efficiently characterize the entire genome sequence of each individual, we performed low-coverage (~5x) whole-genome sequencing, augmented by deep coverage (~100x) sequencing of the exome, and dense (2.5M) single nucleotide polymorphism (SNP) genotyping using the HumanOmni2.5 array.  The data deposited in EGA will include all the Swedish, Finnish, UK, and German samples.","abstract":"The Genetics of Type 2 Diabetes Consortium (GoT2D) is a collaboration between the University of Michigan, the Broad Institute and the Wellcome Trust Centre for Human Genetics. The overall aim is to extend upon recent efforts, such as genome-wide association studies (GWAS) and large scale meta-analyses. While they have proved successful at mapping genomic loci that influence human diseases, like type 2 diabetes, much of the heritability remains unexplained. In this study, we use next generation sequencing and genotyping technologies to query for lower frequency variants in the human genome. Thereby, allowing a deeper characterization of the spectrum of alleles associated with type 2 diabetes risk, and a better assessment of the genes that play a role in the etiology of type 2 diabetes development.  We studied 1,326 T2D cases and 1,331 normoglycemic controls from Northern and Central Europe (Sweden, Finland, UK, and Germany).  To efficiently characterize the entire genome sequence of each individual, we performed low-coverage (~5x) whole-genome sequencing, augmented by deep coverage (~100x) sequencing of the exome, and dense (2.5M) single nucleotide polymorphism (SNP) genotyping using the HumanOmni2.5 array.  The data deposited in EGA will include all the Swedish, Finnish, UK, and German samples.","study_type":"Other","pubmed_ids":[27398621],"external_links":null,"is_released":true,"released_date":"2015-09-08T20:21:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001460","title":"T2D-GENES: Exome sequencing","description":"The Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES) is a large collaboration effort between the University of Michigan, Broad Institute, the Wellcome Trust Centre for Human Genetics, University of Chicago, NIDDK, Texas Biomedical Research Institute, University of Texas Health Science Center, University of North Carolina, Blood Systems Research Institute, and University of Mississippi Medical Center. The goal of this study is to identify genetic variants for type 2 diabetes through multiethnic sequencing studies. In this study, we use next generation sequencing to assess the role of common, low frequency, and rare variants on type 2 diabetes risk. We preformed exome sequencing in 6,546 T2D cases and 6,457 control individuals of multiethnic origin, including individuals of African American, East Asian, South Asian, Hispanic, and European descent.","abstract":"The Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES) is a large collaboration effort between the University of Michigan, Broad Institute, the Wellcome Trust Centre for Human Genetics, University of Chicago, NIDDK, Texas Biomedical Research Institute, University of Texas Health Science Center, University of North Carolina, Blood Systems Research Institute, and University of Mississippi Medical Center. The goal of this study is to identify genetic variants for type 2 diabetes through multiethnic sequencing studies. In this study, we use next generation sequencing to assess the role of common, low frequency, and rare variants on type 2 diabetes risk. We preformed exome sequencing in 6,546 T2D cases and 6,457 control individuals of multiethnic origin, including individuals of African American, East Asian, South Asian, Hispanic, and European descent.","study_type":"Other","pubmed_ids":[27398621],"external_links":null,"is_released":true,"released_date":"2015-09-08T20:21:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001461","title":"Inherited damaging mutations in immune-related genes favour the development of genetically heterogeneous synchronous colorectal cancer.","description":"Synchronous colorectal cancers are physically separated tumours that develop simultaneously in the intestine. To understand how common genetic and environmental backgrounds influence the development of multiple tumours, we conduct a genome-wide comparative analysis of somatic alterations of 20 syCRCs from 10 patients. We show that syCRCs have independent genetic origins, acquire discordant somatic alterations, and follow different clonal developments.","abstract":"Synchronous colorectal cancers are physically separated tumours that develop simultaneously in the intestine. To understand how common genetic and environmental backgrounds influence the development of multiple tumours, we conduct a genome-wide comparative analysis of somatic alterations of 20 syCRCs from 10 patients. We show that syCRCs have independent genetic origins, acquire discordant somatic alterations, and follow different clonal developments.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-09-09T08:12:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001462","title":"Targeting PTPRK-RSPO3 colon tumours promotesdifferentiation and loss of stem-cell function","description":"Colorectal cancer remains a major unmet medical need, promptinglarge-scale genomics efforts in the field to identify moleculardrivers for which targeted therapies might be developed. Wepreviously reported the identification of recurrent translocationsin R-spondin proteins present in a subset of colorectal tumours.Here we show that targeting RSPO3 in PTPRK-RSPO3-fusion positivehuman tumour xenografts inhibits tumour growth andpromotes differentiation. Notably, genes expressed in the stem-cellcompartment of the intestine were among those most sensitive toanti-RSPO3 treatment. This observation, combined with functionalassays, suggests that a stem-cell compartment drives PTPRK-RSPO3colorectal tumour growth and indicates that the therapeutictargeting of stem-cell properties within tumours may be a clinicallyrelevant approach for the treatment of colorectal tumors.","abstract":"Colorectal cancer remains a major unmet medical need, promptinglarge-scale genomics efforts in the field to identify moleculardrivers for which targeted therapies might be developed. Wepreviously reported the identification of recurrent translocationsin R-spondin proteins present in a subset of colorectal tumours.Here we show that targeting RSPO3 in PTPRK-RSPO3-fusion positivehuman tumour xenografts inhibits tumour growth andpromotes differentiation. Notably, genes expressed in the stem-cellcompartment of the intestine were among those most sensitive toanti-RSPO3 treatment. This observation, combined with functionalassays, suggests that a stem-cell compartment drives PTPRK-RSPO3colorectal tumour growth and indicates that the therapeutictargeting of stem-cell properties within tumours may be a clinicallyrelevant approach for the treatment of colorectal tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-09-09T21:30:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001463","title":"Exome-sequencing of human B cell lymphoma cell lines","description":"26 cell lines derived from human Diffuse Large B Cell lymphomas (DLBCL) or Burkit Lymphomas (BL) were subjected to whole exome sequencing. Exome capture was carried out using the SeqCap EZ Exome Library 2.0 kit (Roche/Nimblegen) and 100 bp single-read sequencing was performed on a HiSeq2500 (Illumina). 82% of the coding region was covered at least 30x.","abstract":"26 cell lines derived from human Diffuse Large B Cell lymphomas (DLBCL) or Burkit Lymphomas (BL) were subjected to whole exome sequencing. Exome capture was carried out using the SeqCap EZ Exome Library 2.0 kit (Roche/Nimblegen) and 100 bp single-read sequencing was performed on a HiSeq2500 (Illumina). 82% of the coding region was covered at least 30x.","study_type":"Other","pubmed_ids":[27324824],"external_links":null,"is_released":true,"released_date":"2015-09-10T15:52:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001464","title":"Classification of glioblastoma based on patient-derived cell screening","description":"Temozolomide (TMZ) is an important component of first-line regimen for newly diagnosed IDH wild type primary glioblastomas (GBMs). The limited accuracy of MGMT promoter methylation in predicting benefit from TMZ has hampered clinical application. To allow better prospective selection of patients with a high likelihood of response to TMZ, the predictive value of in vitro susceptibility to TMZ using patient-derived GBM stem cells (GSC)-based screen was evaluated, and clinical relevance of the signature predictive of TMZ therapeutic benefit were validated. TMZ cytotoxicity testing of 35 GSCs from newly diagnosed GBMs showed differential responses to TMZ, stratifying GSCs into responders and non-responders. TMZ sensitivity in vitro was closely correlated with clinical benefits from TMZ in parental GBMs as well as the effects on clonogenic potential and xenografts growth. Subsequently, TMZ-sensitivity gene signature reflecting tumor responses to TMZ was finally identified using 35 matched pairs of primary and recurrent GBMs, which included 10 genes corresponding to up-regulation in TMZ-responder and a significant decrease during progression, and 136 genes corresponding to up-regulation in TMZ-non-responder and persistence throughout progression. This TMZ-sensitivity signature compared favorably to MGMT status as an outcome predictor in TMZ treated patients with newly-diagnosed IDH wild-type GBM from TCGA cohort. Finally, targeting phosphoinositide 3-kinase (PI3K)/Akt pathway enriched in TMZ-non-responders potentiated cytotoxicity of TMZ in TMZ-resistant GSCs. Taken together, the combined use of preclinical TMZ testing on patient-derived GSCs and clinically relevant TMZ sensitivity signature for therapeutic decision guidance of newly diagnosed GBMs.","abstract":"Temozolomide (TMZ) is an important component of first-line regimen for newly diagnosed IDH wild type primary glioblastomas (GBMs). The limited accuracy of MGMT promoter methylation in predicting benefit from TMZ has hampered clinical application. To allow better prospective selection of patients with a high likelihood of response to TMZ, the predictive value of in vitro susceptibility to TMZ using patient-derived GBM stem cells (GSC)-based screen was evaluated, and clinical relevance of the signature predictive of TMZ therapeutic benefit were validated. TMZ cytotoxicity testing of 35 GSCs from newly diagnosed GBMs showed differential responses to TMZ, stratifying GSCs into responders and non-responders. TMZ sensitivity in vitro was closely correlated with clinical benefits from TMZ in parental GBMs as well as the effects on clonogenic potential and xenografts growth. Subsequently, TMZ-sensitivity gene signature reflecting tumor responses to TMZ was finally identified using 35 matched pairs of primary and recurrent GBMs, which included 10 genes corresponding to up-regulation in TMZ-responder and a significant decrease during progression, and 136 genes corresponding to up-regulation in TMZ-non-responder and persistence throughout progression. This TMZ-sensitivity signature compared favorably to MGMT status as an outcome predictor in TMZ treated patients with newly-diagnosed IDH wild-type GBM from TCGA cohort. Finally, targeting phosphoinositide 3-kinase (PI3K)/Akt pathway enriched in TMZ-non-responders potentiated cytotoxicity of TMZ in TMZ-resistant GSCs. Taken together, the combined use of preclinical TMZ testing on patient-derived GSCs and clinically relevant TMZ sensitivity signature for therapeutic decision guidance of newly diagnosed GBMs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001465","title":"HipSci - Human Induced Pluripotent Stem Cells Initiative","description":"Human induced pluripotent stem (iPS) cells can be generated from adult tissues and differentiated into a range of specific cell types (Yamanaka and Blau, 2010).   They therefore provide unprecedented opportunities for investigating disease mechanisms and understanding the phenotypic consequences of genetic variation within the normal population.  HipSci brings  together diverse constitutents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.   Between 2013 and 2016 we aim to generate iPS cells from over 500  healthy individuals and 500 individuals with genetic disease. We will then use these cells to discover how genomic variation impacts on cellular phenotype and identify new disease mechanisms.  Strong links with NHS investigators will ensure that studies on the disease-associated cell lines will be linked to extensive clinical information.  Further key features of the project are an open access model of data sharing; engagement of the wider clinical genetics community in selecting patient samples; and provision of dedicated laboratory space for collaborative cell phenotyping and differentiation.","abstract":"Human induced pluripotent stem (iPS) cells can be generated from adult tissues and differentiated into a range of specific cell types (Yamanaka and Blau, 2010).   They therefore provide unprecedented opportunities for investigating disease mechanisms and understanding the phenotypic consequences of genetic variation within the normal population.  HipSci brings  together diverse constitutents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.   Between 2013 and 2016 we aim to generate iPS cells from over 500  healthy individuals and 500 individuals with genetic disease. We will then use these cells to discover how genomic variation impacts on cellular phenotype and identify new disease mechanisms.  Strong links with NHS investigators will ensure that studies on the disease-associated cell lines will be linked to extensive clinical information.  Further key features of the project are an open access model of data sharing; engagement of the wider clinical genetics community in selecting patient samples; and provision of dedicated laboratory space for collaborative cell phenotyping and differentiation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-09-11T12:23:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001466","title":"Sequencing of serial plasma and multiregional tumor samples in a patient with metastatic breast cancer","description":"Circulating tumor DNA analysis can be used to track tumor burden and analyze cancer genomes non-invasively but the extent to which it represents metastatic heterogeneity is unknown. Here, we follow a patient with metastatic ER and HER2 positive breast cancer receiving two lines of targeted therapy over 3 years. We characterize genomic architecture and infer clonal evolution in 8 tumor biopsies and 9 plasma samples collected over 1,193 days of clinical follow-up using exome and targeted amplicon sequencing.","abstract":"Circulating tumor DNA analysis can be used to track tumor burden and analyze cancer genomes non-invasively but the extent to which it represents metastatic heterogeneity is unknown. Here, we follow a patient with metastatic ER and HER2 positive breast cancer receiving two lines of targeted therapy over 3 years. We characterize genomic architecture and infer clonal evolution in 8 tumor biopsies and 9 plasma samples collected over 1,193 days of clinical follow-up using exome and targeted amplicon sequencing.","study_type":"Other","pubmed_ids":[26530965],"external_links":null,"is_released":true,"released_date":"2015-09-12T22:25:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001467","title":"Helleday_MYC_WGS","description":"This study is to look at the effect of Myc and oxygen conditions on mutational signatures, to help establish causative roles for particular signatures.","abstract":"This study is to look at the effect of Myc and oxygen conditions on mutational signatures, to help establish causative roles for particular signatures.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001468","title":"Tue_Sep_15_09_35_29_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001469","title":"Tue_Sep_15_09_36_17_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001470","title":"Tue_Sep_15_09_36_21_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001471","title":"Genome_wide_association_study_of_vaccine_responses_in_infants_living_in_the_Developing_World__VaccGene___African_Cohorts__South_Africa__second_set_","description":"It is estimated that up to 70% of the variability in response to some vaccines administered inchildhood is inherited but the identification of the genetic factors responsible for this variationhas not yet been prioritised. We have started one of the largest genome-wide associationstudies of vaccine responses ever undertaken, which will provide unparalleled power toidentify the genetic factors associated with the response to all of the most commonly usedchildhood vaccines worldwide.  In the first phase we analysed 2,181,930 autosomal markersgenotyped in 1,391 Ugandan children enrolled in the Entebbe Mother and Baby cohort study.Strong Class II HLA associations were observed with response to diphtheria toxin, pertussistoxin, pertussis pertactin, and pertussis filamentous haemagglutinin adhesin and we havenow replicated these findings in 750 infants from South Africa and 350 infants from BurkinaFaso. No associations of genome-wide significance were observed in HLA with response totetanus toxin, or against attenuated measles or the conjugated Haemophilus influenzaevaccines. In addition to the planned addition of 620 infants recruited in Bangladesh outlined ina separate prelim we would also like to genotype an outstanding 260 individuals from SouthAfrica who were not genotyped in the first round owing to unavailability of the samples at thetime of genotyping. These samples are now available in-house and we have phenotype datafor all of these individuals. Including these individuals would further increase sample size forthe meta-analysis and would allow for better characterization of the HLA haplotypes bothamongst the South African sample set but also across the dataset in general.Funds from a Wellcome Trust Research Training Fellowship grant held at the University ofOxford by Dr Alexander Mentzer, who has been collaborating closely on this GWAS, willcover the genotyping of these 260 samples on the Illumina MEGA2 array. All DNAs havealready undergone quality control and are ready to be processed.The results from this large-scale analysis will be used to understand why HLA is stronglyassociated with some, but not all, toxoid vaccine responses and to identify the other elementsof the immune system associated with inter-individual variability to response to multiplevaccines. These results may have important implications for future vaccine design.","abstract":"It is estimated that up to 70% of the variability in response to some vaccines administered inchildhood is inherited but the identification of the genetic factors responsible for this variationhas not yet been prioritised. We have started one of the largest genome-wide associationstudies of vaccine responses ever undertaken, which will provide unparalleled power toidentify the genetic factors associated with the response to all of the most commonly usedchildhood vaccines worldwide.  In the first phase we analysed 2,181,930 autosomal markersgenotyped in 1,391 Ugandan children enrolled in the Entebbe Mother and Baby cohort study.Strong Class II HLA associations were observed with response to diphtheria toxin, pertussistoxin, pertussis pertactin, and pertussis filamentous haemagglutinin adhesin and we havenow replicated these findings in 750 infants from South Africa and 350 infants from BurkinaFaso. No associations of genome-wide significance were observed in HLA with response totetanus toxin, or against attenuated measles or the conjugated Haemophilus influenzaevaccines. In addition to the planned addition of 620 infants recruited in Bangladesh we would also like to genotype an outstanding 260 individuals from SouthAfrica who were not genotyped in the first round owing to unavailability of the samples at thetime of genotyping. Including these individuals would further increase sample size forthe meta-analysis and would allow for better characterization of the HLA haplotypes bothamongst the South African sample set but also across the dataset in general.The results from this large-scale analysis will be used to understand why HLA is strongly associated with some, but not all, toxoid vaccine responses and to identify the other elementsof the immune system associated with inter-individual variability to response to multiplevaccines. These results may have important implications for future vaccine design.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001472","title":"Analysis of the lung gene expression profile in COPD","description":"Samples obtained from patients with COPD and from controls by bronchoscopy from the lung were subjected to RNA seq.","abstract":"Samples obtained from patients with COPD and from controls by bronchoscopy from the lung were subjected to RNA seq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-09-18T15:50:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001473","title":"Whole genome and transcriptome analysis of medullary thyroid cancer","description":"Medullary thyroid cancer is the neoplasm of the calcitonin-producing parafollicular cells of the thyroid gland. The hormone calcitonin acts to lower the blood calcium level, counteracting the effects of the parathyroid hormone; it can also serve as a biomarker for the presence or recurrence of medullary thyroid cancer. Surgery is the only curative treatment for this cancer. Targeted therapeutics vandetanib and cabozantinib are approved for the treatment of aggressive and metastatic tumors that are not amenable to surgery. The use of these multikinase inhibitors are supported by the observed overactivation of the RET oncoprotein in a large sub-population of medullary thyroid cancers; however, not all patients carry oncogenic alterations of this kinase. Hence, there is a need for molecular characterization of medullary tumors on the genomic scale with the aim of identifying targetable mutations. Here, we describe the genomic profiles of two medullary thyroid cancers and report the presence of a putative oncogenic BRAF fusion in one. Such alterations previously observed in other malignancies and known targets of available drugs, can benefit patients who currently have no therapy options.","abstract":"Medullary thyroid cancer is the neoplasm of the calcitonin-producing parafollicular cells of the thyroid gland. The hormone calcitonin acts to lower the blood calcium level, counteracting the effects of the parathyroid hormone; it can also serve as a biomarker for the presence or recurrence of medullary thyroid cancer. Surgery is the only curative treatment for this cancer. Targeted therapeutics vandetanib and cabozantinib are approved for the treatment of aggressive and metastatic tumors that are not amenable to surgery. The use of these multikinase inhibitors are supported by the observed overactivation of the RET oncoprotein in a large sub-population of medullary thyroid cancers; however, not all patients carry oncogenic alterations of this kinase. Hence, there is a need for molecular characterization of medullary tumors on the genomic scale with the aim of identifying targetable mutations. Here, we describe the genomic profiles of two medullary thyroid cancers and report the presence of a putative oncogenic BRAF fusion in one. Such alterations previously observed in other malignancies and known targets of available drugs, can benefit patients who currently have no therapy options.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-09-18T23:43:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001474","title":"WGS-Lung Cancer sample 30 pair","description":"This study includes 30 paired samples of Korean Lung Cancer paitients. 30 Lung Cancer samples are paired with each normal(Saliva derived for control) sequencing data.The results of this WGS study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.","abstract":"This study includes 30 paired samples of Korean Lung Cancer paitients. 30 Lung Cancer samples are paired with each normal(Saliva derived for control) sequencing data.The results of this WGS study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-09-20T02:18:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001475","title":"71 Whole-exome sequencing of Esophageal Squamous Cell Carcinoma on Chinese Patients","description":"Esophageal Squamous Cell Carcinoma (ESCC) is one of the deadliest cancers worldwide. We performed 71 Whole-exome sequencing of Esophageal Squamous Cell Carcinoma on Chinese Patients.","abstract":"Esophageal Squamous Cell Carcinoma (ESCC) is one of the deadliest cancers worldwide. We performed 71 Whole-exome sequencing of Esophageal Squamous Cell Carcinoma on Chinese Patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-09-20T03:36:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001476","title":"TraIT Cell Line use case","description":"Experimental data collected from a set of cell lines. To be used as a test for pipelines and infrastructure.","abstract":"Experimental data collected from a set of cell lines. To be used as a test for pipelines and infrastructure.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-09-21T13:17:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001477","title":"Understanding_the_genetics_of_uncontrolled_airway_disease__focusing_on_bronchiectasis_","description":"This project will provide exome sequencing of defined sub-populations of bronchiectasis patients.","abstract":"Bronchiectasis is a disease in which there is permanent enlargement of parts of the airwaysof the lung. Symptoms typically include a chronic cough with sputum production. Othersymptoms include shortness of breath, coughing up blood and chest pain. Those with thedisease often get frequent lung infections. Bronchiectasis may result from a number ofinfective and acquired causes, including pneumonia, tuberculosis, immune system problems,and cystic fibrosis. There is a current need to understand the genetic/genomic mechanismsunderlying the disease and there is a clear unmet medical need to identify therapeutics whichcan treat the different manifestation of bronchiectasis. This project will provide exome sequencing of defined sub-populations of bronchiectasis patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001478","title":"Genotyping and imputation of 134 brain samples from the UBKEC consortium.","description":"Brain samples were obtained from 134 individuals of European descent. All individuals were neurologically normal during life and confirmed to be neuropathologically normal by a consultant neuropathologist using histology performed on sections prepared from paraffin-embedded brain tissue blocks. The individuals sampled had a mean age at death of 59 years old (range 16–102), were mostly men (74.5%) and the most common cause of death was ischemic heart disease (44.7%).  Genomic DNA was extracted from sub-dissected samples (100–200 mg) of human post-mortem brain tissue using Qiagen’s DNeasy Blood &amp; Tissue Kit (Qiagen,UK). All samples were genotyped on the Illumina Infinium Omni1-Quad BeadChip and on the Immunochip, a custom genotyping array designed for the fine-mapping of auto-immune disorders1,49. The BeadChips were scanned using an iScan (Illumina, USA) with an AutoLoader (Illumina, USA). GenomeStudio v.1.8.X (Illumina, USA) was used for analysing the data and generating SNP calls. After standard quality controls (removal of suspected non-European descent individuals, samples with call rate &lt; 95% and checks on reported sex status, cryptic relatedness, autosomal heterozygosity rate check, monomorphic SNPs or call rate &lt; 95%, no genomic position info or redundant SNPs, pvalue for deviation from HWE &lt; 0.0001, genotyping call rate &lt; 95%, less than 2 heterozygotes present, mismatching alleles 1000G even after allowing for strand), imputation was performed using MaCH 50,51 and minimac (http://genome.sph.umich.edu/wiki/Minimac) using the European panel of the 1000 Genomes Project (March 2012: Integrated Phase I haplotype release version 3, based on the 2010-11 data freeze and 2012-03-14 haplotypes). We used the resulting 5,878,211 SNPs and 576,942 indels with good post-imputation quality (Rsq &gt; 0.50) and minor allele frequency of at least 5%.","abstract":"Brain samples were obtained from 134 individuals of European descent. All individuals were neurologically normal during life and confirmed to be neuropathologically normal by a consultant neuropathologist using histology performed on sections prepared from paraffin-embedded brain tissue blocks. The individuals sampled had a mean age at death of 59 years old (range 16–102), were mostly men (74.5%) and the most common cause of death was ischemic heart disease (44.7%).  Genomic DNA was extracted from sub-dissected samples (100–200 mg) of human post-mortem brain tissue using Qiagen’s DNeasy Blood &amp; Tissue Kit (Qiagen,UK). All samples were genotyped on the Illumina Infinium Omni1-Quad BeadChip and on the Immunochip, a custom genotyping array designed for the fine-mapping of auto-immune disorders1,49. The BeadChips were scanned using an iScan (Illumina, USA) with an AutoLoader (Illumina, USA). GenomeStudio v.1.8.X (Illumina, USA) was used for analysing the data and generating SNP calls. After standard quality controls (removal of suspected non-European descent individuals, samples with call rate &lt; 95% and checks on reported sex status, cryptic relatedness, autosomal heterozygosity rate check, monomorphic SNPs or call rate &lt; 95%, no genomic position info or redundant SNPs, pvalue for deviation from HWE &lt; 0.0001, genotyping call rate &lt; 95%, less than 2 heterozygotes present, mismatching alleles 1000G even after allowing for strand), imputation was performed using MaCH 50,51 and minimac (http://genome.sph.umich.edu/wiki/Minimac) using the European panel of the 1000 Genomes Project (March 2012: Integrated Phase I haplotype release version 3, based on the 2010-11 data freeze and 2012-03-14 haplotypes). We used the resulting 5,878,211 SNPs and 576,942 indels with good post-imputation quality (Rsq &gt; 0.50) and minor allele frequency of at least 5%.","study_type":"Other","pubmed_ids":[25174004],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001479","title":"TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors","description":"Whole genome sequencing detected structural rearrangements of TERT in 17/75 high stage neuroblastoma with 5 cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted immediate up- and down-stream regions of TERT, placing in 7 cases a super-enhancer close to the breakpoints. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high stage neuroblastoma, each associated with very poor prognosis. This submission contains all newly sequenced samples only.","abstract":"Whole genome sequencing detected structural rearrangements of TERT in 17/75 high stage neuroblastoma with 5 cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted immediate up- and down-stream regions of TERT, placing in 7 cases a super-enhancer close to the breakpoints. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high stage neuroblastoma, each associated with very poor prognosis. This submission contains all newly sequenced samples only.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-09-28T12:48:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001480","title":"Mon_Sep_28_13_55_13_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001481","title":"Mon_Sep_28_13_56_16_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001482","title":"Mon_Sep_28_13_56_20_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001483","title":"Mon_Sep_28_13_59_55_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001484","title":"Mon_Sep_28_14_00_36_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001485","title":"Mon_Sep_28_14_00_39_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001486","title":"Transcriptomics_of_human_olfactory_mucosa","description":"The olfactory gene repertoire is largely species-specific, shaped by the nature and necessityof chemosensory information for survival in each species' niche. We are intrigued by thisinterspecific variation and started to investigate the olfactory transcriptome in primates forevidence of selection at the level of receptor gene choice. Having collected this data fromtwo primates, we now wish to extend the analysis to humans.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"In this study RNA was extracted from the olfactory mucosa of three humans. The RNA was sequenced using the Illumina Hiseq2500 platform.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-09-29T08:43:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001487","title":"Whole-genome sequencing in 14  cases and whole-exome sequencing in 90 cases of Chinese ESCC","description":"Esophageal cancer is one of the most aggressive cancers and the sixth leading cause of cancer death worldwide1. Approximately 70% of the global esophageal cancers occur in China and over 90% histopathological forms of this disease are esophageal squamous cell carcinoma (ESCC)2-3. Currently, there are limited clinical approaches for early diagnosis and treatment for ESCC, resulting in a 10% 5-year survival rate for the patients. Meanwhile, the full repertoire of genomic events leading to the pathogenesis of ESCC remains unclear. Here we show a comprehensive genomic analysis in 158 ESCC cases, as part of the International Cancer Genome Consortium (ICGC) Research Projects (http://icgc.org/icgc/cgp/72/371/1001734). We conducted whole-genome sequencing in 14 ESCC cases and whole-exome sequencing in 90 cases.","abstract":"Esophageal cancer is one of the most aggressive cancers and the sixth leading cause of cancer death worldwide1. Approximately 70% of the global esophageal cancers occur in China and over 90% histopathological forms of this disease are esophageal squamous cell carcinoma (ESCC)2-3. Currently, there are limited clinical approaches for early diagnosis and treatment for ESCC, resulting in a 10% 5-year survival rate for the patients. Meanwhile, the full repertoire of genomic events leading to the pathogenesis of ESCC remains unclear. Here we show a comprehensive genomic analysis in 158 ESCC cases, as part of the International Cancer Genome Consortium (ICGC) Research Projects (http://icgc.org/icgc/cgp/72/371/1001734). We conducted whole-genome sequencing in 14 ESCC cases and whole-exome sequencing in 90 cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-09-29T08:56:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001488","title":"Wed_Sep_30_11_16_08_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001489","title":"Wed_Sep_30_11_17_13_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001490","title":"Wed_Sep_30_11_17_59_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001491","title":"Wed_Sep_30_11_18_03_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001492","title":"Wed_Sep_30_11_26_07_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001493","title":"Wed_Sep_30_11_26_52_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001494","title":"Wed_Sep_30_11_26_56_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001495","title":"Wed_Sep_30_11_29_28_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001496","title":"Wed_Sep_30_11_30_20_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001497","title":"Wed_Sep_30_11_30_24_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001498","title":"Wed_Sep_30_11_40_59_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001499","title":"Wed_Sep_30_11_41_49_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001500","title":"Wed_Sep_30_11_41_53_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001501","title":"TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism","description":"DNA lesions encountered by replicative polymerases threaten genome stability and cell cycle progression. Here we report the identification of mutations in TRAIP, encoding an E3 RING ubiquitin ligase, in patients with microcephalic primordial dwarfism/Seckel syndrome. We establish that TRAIP relocalizes to sites of DNA damage where it is required for optimal phosphorylation of H2AX and RPA2 during S-phase in response to UV irradiation, as well as fork progression through UV-induced DNA lesions. TRAIP is necessary for efficient cell cycle progression and mutations in TRAIP therefore limit cellular proliferation, providing a potential mechanism for microcephaly and dwarfism phenotypes. Human genetics thus identifies TRAIP as a novel component of the DNA damage response to replication-blocking DNA lesions.","abstract":"DNA lesions encountered by replicative polymerases threaten genome stability and cell cycle progression. Here we report the identification of mutations in TRAIP, encoding an E3 RING ubiquitin ligase, in patients with microcephalic primordial dwarfism/Seckel syndrome. We establish that TRAIP relocalizes to sites of DNA damage where it is required for optimal phosphorylation of H2AX and RPA2 during S-phase in response to UV irradiation, as well as fork progression through UV-induced DNA lesions. TRAIP is necessary for efficient cell cycle progression and mutations in TRAIP therefore limit cellular proliferation, providing a potential mechanism for microcephaly and dwarfism phenotypes. Human genetics thus identifies TRAIP as a novel component of the DNA damage response to replication-blocking DNA lesions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-09-30T12:31:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001502","title":"Wed_Sep_30_13_14_50_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001503","title":"Wed_Sep_30_13_15_34_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001504","title":"Wed_Sep_30_13_15_38_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001505","title":"Wed_Sep_30_13_18_54_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001506","title":"Wed_Sep_30_13_19_36_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001507","title":"Wed_Sep_30_13_19_40_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001508","title":"Wed_Sep_30_13_34_57_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001509","title":"Wed_Sep_30_13_35_44_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001510","title":"Wed_Sep_30_13_35_48_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001511","title":"Wed_Sep_30_13_41_14_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001512","title":"Wed_Sep_30_13_42_00_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001513","title":"Wed_Sep_30_13_42_04_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001514","title":"BLUEPRINT Small RNA-Seq study in cells from venous and coord blood samples","description":"BLUEPRINT Small RNA-Seq study in cells from venous and coord blood samples","abstract":"BLUEPRINT Small RNA-Seq study in cells from venous and coord blood samples","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001515","title":"The HLA-DQβ1 insertion is a strong achalasia risk factor  and displays a geospatial north-south gradient among Europeans","description":"Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an 8 amino acid insertion in the cytoplasmic tail of HLA-DQβ1 as strong achalasia risk factor in a sample set from Central Europe, Italy, and Spain. Here, we tested whether the HLA-DQβ1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P = 1.84×10-04, Sweden P = 7.44×10-05). Combining all five European data sets – Central Europe, Italy, Spain, Poland, and Sweden – the insertion is achalasia associated with Pcombined = 1.67×10-35. In addition, we observe that the frequency of the insertion shows a geospatial north-south gradient. The insertion is less common in northern (around 6-7% in patients and 2% in controls from Sweden and Poland) compared to southern Europeans (around 16% in patients and 8% in controls from Italy) and shows a stronger attributable risk (AR) in the southern European population. Our study provides evidence that the prevalence of achalasia may differ between populations.","abstract":"Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an 8 amino acid insertion in the cytoplasmic tail of HLA-DQβ1 as strong achalasia risk factor in a sample set from Central Europe, Italy, and Spain. Here, we tested whether the HLA-DQβ1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P = 1.84×10-04, Sweden P = 7.44×10-05). Combining all five European data sets – Central Europe, Italy, Spain, Poland, and Sweden – the insertion is achalasia associated with Pcombined = 1.67×10-35. In addition, we observe that the frequency of the insertion shows a geospatial north-south gradient. The insertion is less common in northern (around 6-7% in patients and 2% in controls from Sweden and Poland) compared to southern Europeans (around 16% in patients and 8% in controls from Italy) and shows a stronger attributable risk (AR) in the southern European population. Our study provides evidence that the prevalence of achalasia may differ between populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-09-30T15:50:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001516","title":"Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study","description":"This data comes from a genome-wide association study in 1090 cases of scarring trachoma and 1531 controls from a non-selected multi-ethnic sampling of The Gambia. The data constitutes hard base calls at 1457295 features from the HumanOmni2.5-8 (Omni2.5) BeadChip. Three genotype-calling algorithms were used : Illuminus (Bioinformatics 2007, 23:2741–6), GenCall (Patent US7035740, 2006) and GenoSNP (Bioinformatics 2008, 24:2209–14). Data from each calling algorithm was filtered to retain only SNPs with a call rate ≥ 0.98. To obtain a merged set of SNPs, all genotypes that matched across call-sets were retained, whilst those that mismatched between call-sets were set to missing. Genotypes that were present in one call set and missing in others were also retained. The merged SNP set contained 1467876 SNPs, which were filtered for call rate ≥ 0.99 and Hardy-Weinberg equilibrium P value &lt; 5 x 10-8.   The case and control groups were approximately equivalent with respect to gender and ethnicity. 70% of cases and 63% of controls were female. Self-described ethnic composition of the cases was 29% Jola, 27% Mandinka, 21% Wolof, 10% Fula and 13% other/no data. In controls the composition was 25% Jola, 24% Mandinka, 21% Wolof, 8% Fula and 22% other/no data. Median age was 49 (range 32-60) in cases and 37 (range 12-52) in controls (t = -3.6019, P = 0.0003). This data set has substantial levels of population structure, which reflects extensive networks of pairwise kinship between participants. First pass tests of association in EMMAX (Nat Genet 2010, 42:348–54) led to genome-wide deflation of the test statistics (λ = 0.982 SE = 1.74e-05) that could be directly attributed to the differing age and gender distributions between cases and controls. Modelling the phenotype to adjust for age and gender successfully controlled for this and no genome-wide deviation from the null was subsequently observed (λ = 1.001, SE = 8.7 x 10-7). Neither principal components analysis (PCA) nor tests of proportional identity by state (IBS) variance in PLINK identified significant levels of within or between group genetic variance. The phenotypes submitted in the phenotypes file include both uncorrected (case/control status) and corrected (age and gender corrected case/control status) phenotypes, as well as age and self-described ethnicity.","abstract":"This data comes from a genome-wide association study in 1090 cases of scarring trachoma and 1531 controls from a non-selected multi-ethnic sampling of The Gambia. The data constitutes hard base calls at 1457295 features from the HumanOmni2.5-8 (Omni2.5) BeadChip. Three genotype-calling algorithms were used : Illuminus (Bioinformatics 2007, 23:2741–6), GenCall (Patent US7035740, 2006) and GenoSNP (Bioinformatics 2008, 24:2209–14). Data from each calling algorithm was filtered to retain only SNPs with a call rate ≥ 0.98. To obtain a merged set of SNPs, all genotypes that matched across call-sets were retained, whilst those that mismatched between call-sets were set to missing. Genotypes that were present in one call set and missing in others were also retained. The merged SNP set contained 1467876 SNPs, which were filtered for call rate ≥ 0.99 and Hardy-Weinberg equilibrium P value &lt; 5 x 10-8.   The case and control groups were approximately equivalent with respect to gender and ethnicity. 70% of cases and 63% of controls were female. Self-described ethnic composition of the cases was 29% Jola, 27% Mandinka, 21% Wolof, 10% Fula and 13% other/no data. In controls the composition was 25% Jola, 24% Mandinka, 21% Wolof, 8% Fula and 22% other/no data. Median age was 49 (range 32-60) in cases and 37 (range 12-52) in controls (t = -3.6019, P = 0.0003). This data set has substantial levels of population structure, which reflects extensive networks of pairwise kinship between participants. First pass tests of association in EMMAX (Nat Genet 2010, 42:348–54) led to genome-wide deflation of the test statistics (λ = 0.982 SE = 1.74e-05) that could be directly attributed to the differing age and gender distributions between cases and controls. Modelling the phenotype to adjust for age and gender successfully controlled for this and no genome-wide deviation from the null was subsequently observed (λ = 1.001, SE = 8.7 x 10-7). Neither principal components analysis (PCA) nor tests of proportional identity by state (IBS) variance in PLINK identified significant levels of within or between group genetic variance. The phenotypes submitted in the phenotypes file include both uncorrected (case/control status) and corrected (age and gender corrected case/control status) phenotypes, as well as age and self-described ethnicity.","study_type":"Other","pubmed_ids":[26616738],"external_links":null,"is_released":true,"released_date":"2015-09-30T16:03:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001517","title":"Whole-exome sequencing of thyroid cancer","description":"We have sequenced 35 thyroid cancer samples, 34 of them have paired normal samples.","abstract":"We have sequenced 35 thyroid cancer samples, 34 of them have paired normal samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001518","title":"Whole-exome sequencing of 46 pairs thyroid cancer","description":"We have sequenced 46 pairs of thyroid cancer samples.","abstract":"We have sequenced 46 pairs of thyroid cancer samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001519","title":"Glioblastoma_CRISPR_Screen","description":"This is an in vitro genome-wide CRISPR/cas9 screen in human glioblastoma stem cells, screening for genes essential for survival of these cells. These cells express cas9 and have been transfected with a guide RNA library causing gene knockouts. We will analyse the sequencing data for depletion of guide RNAs.","abstract":"Human glioblastoma stem cells are thought to be extremely important in causing recurrence of this aggressive brain tumour and resistance to therapy. However, little is known of the genes needed for these cells to survive. We are performing a genome-wide CRISPR/cas9 screen for the genes essential for proliferation of these cells in vitro. Such genes will have depletion of their guide RNAs, and these candidates will be validated in downstream in vitro and in vivo experimental work, representing potential novel therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-10-01T10:24:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001520","title":"BAP1_sequence_of_uveal_melanoma_cell_lines","description":"Detection of BAP1 mutations in DNA from 3 uveal melanoma cell lines.","abstract":"Detection of BAP1 mutations in DNA from 3 uveal melanoma cell lines.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-10-01T10:40:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001521","title":"S_CORT_Stratification_in_COloRecTal_cancer_","description":"Colorectal cancer samples will be submitted for Illumina sequencing using a custom capture of 116 genes implicated in colorectal tumourigenesis. Driver mutations will be detected and ultimately correlated with phenotypic data.","abstract":"S-CORT will utilise clinically annotated pathological samples  to: 1. develop new predictive  tests, with a particular focus on mCRC/rectal cancer; 2. address 4 highly relevant clinical questions: 1. Can we predict which patients will respond to oxaliplatin treatment?2. Can we predict which patients respond to standard  or modified radiotherapy (RT) strategies? 3. Does stratification in early rectal/colon cancer predict risk of  invasion, thus informing either radical  or organ preserving treatment options?  4. Can we develop better biomarkers to predict response to novel molecularly guided approaches in stratified CRC cohorts?","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-10-01T10:48:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001522","title":"Thu_Oct_01_15_35_37_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001523","title":"Thu_Oct_01_15_36_22_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001524","title":"Thu_Oct_01_15_36_26_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001525","title":"Fri_Oct_02_09_29_09_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001526","title":"Fri_Oct_02_09_30_01_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001527","title":"Fri_Oct_02_09_30_05_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001528","title":"Mon_Oct_05_10_11_17_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001529","title":"Mon_Oct_05_10_12_03_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001530","title":"Mon_Oct_05_10_12_06_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001531","title":"Mon_Oct_05_10_15_18_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001532","title":"Mon_Oct_05_10_16_02_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001533","title":"Mon_Oct_05_10_16_06_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001534","title":"Mon_Oct_05_11_24_01_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001535","title":"Mon_Oct_05_11_24_42_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001536","title":"Mon_Oct_05_11_24_46_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001537","title":"RNA_expression_profiling_of_melanoma_patient_derived_xenograft","description":"Patient-derived xenografts (n=96) were derived from metastatic melanoma patients. RNA expression profiling will be preformed to study  1. HLA-typing and  2. the effect of the tumour microenvironment on tumour growthThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Patient-derived xenografts (n=96) were derived from metastatic melanoma patients. RNA expression profiling will be preformed to study  1. HLA-typing and  2. the effect of the tumour microenvironment on tumour growth","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-10-06T09:20:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001538","title":"Human_Evolution_3C","description":"This project aims to sequence whole genomes of individuals with Aboriginal Australian ancestry. The genetic history of Australian Aboriginals is thought to be a key component for the understanding of human migrations outside of Africa, yet very few genetic studies have been done on this population to date. Likewise, little is known about the current day genetic landscape of Australian Aboriginals. The novel feature of these individuals is that some carry self-stated Tasmanian ancestry. By sequencing whole genomes and comparing them to other genetic data from Australia and the rest of the world this study will contribute to an increased understanding of the genetics of this population.","abstract":"The genetic history of the Australian Aboriginal people is thought to be a key component for the understanding of human migrations outside of Africa, yet very few genetic studies have been done on this population to date and little is known about the current day genetic landscape of Australian Aboriginals. We aim to sequence whole genomes of Tasmanian ancestry and compare them to other genetic data from Australia and the rest of the world in order to understand their genetic make-up.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001539","title":"A comprehensive assessment of somatic mutation detection in cancer using whole genome sequencing","description":"As whole genome sequencing for cancer genome analysis becomes a clinical tool, a full understanding of the variables affecting sequencing analysis output is required. Using tumor-normal sample pairs from two different types of cancer, chronic lymphocytic leukemia and medulloblastoma, we conducted a benchmarking exercise within the context of the International Cancer Genome Consortium. We compare sequencing methods, analysis pipelines, and even validation methods. Here we show that using PCR-free methods and increasing sequencing depth to ~100x showed benefits, as long as the tumor:control coverage ratio remains balanced. We observe widely varying mutation call rates and low concordance among analysis pipelines, reflecting the artifact-prone nature of the raw data and lack of standards for dealing with the artifacts. However, armed with the benchmark mutation set we have created, we show that many issues are in fact easy to remedy and have an immediate positive impact on mutation detection accuracy.","abstract":"As whole genome sequencing for cancer genome analysis becomes a clinical tool, a full understanding of the variables affecting sequencing analysis output is required. Using tumor-normal sample pairs from two different types of cancer, chronic lymphocytic leukemia and medulloblastoma, we conducted a benchmarking exercise within the context of the International Cancer Genome Consortium. We compare sequencing methods, analysis pipelines, and even validation methods. Here we show that using PCR-free methods and increasing sequencing depth to ~100x showed benefits, as long as the tumor:control coverage ratio remains balanced. We observe widely varying mutation call rates and low concordance among analysis pipelines, reflecting the artifact-prone nature of the raw data and lack of standards for dealing with the artifacts. However, armed with the benchmark mutation set we have created, we show that many issues are in fact easy to remedy and have an immediate positive impact on mutation detection accuracy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-10-07T12:46:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001540","title":"Genomic analysis reveals novel secondary drivers and progression pathways in skin basal cell carcinoma","description":"Basal cell carcinoma of the skin (BCC) is the most common malignant neoplasm in humans. BCC is primarily driven by the aberrant activation of the Sonic Hedgehog (Hh) pathway. However, its extensive phenotypical variation remains to be explained. The genetic profiling of 293 BCCs revealed the highest mutation rate observed in cancer (65 Mutations/Mb), with strong prevalence of UV-light signature mutations. 85% of BCCs harbored mutations in Hh pathway genes: mutually exclusive PTCH1 (73%) and SMO (20%) (P=6.6x10-8), SUFU (8%), and in TP53 (61%). 85% of BCCs also harbored secondary driver mutations in other genes implicated in BCC tumorigenesis. Recurrent secondary driver mutations were observed in MYCN (30%), PPP6C (15%), STK19 (10%), LATS1 (8%), ERBB2 (4%), PIK3CA (2%), RAC1 (1%) and N/K/H-RAS (2%). Loss of function (LoF) and deleterious missense mutations were observed in PTPN14 (23%), RB1 (8%) and FBXW7 (5%). In line with the mutational profiles detected by RNAseq, we observed activation of the Hh pathway as well as upregulation of target genes of the Hippo-YAP pathway and activation of MYCN target genes. The functional analysis of the novel tumorigenic driver mutations in MYCN, PTPN14 and LATS1 demonstrates their relevance in BCC tumorigenesis and provides an expanded molecular understanding of BCC.","abstract":"Basal cell carcinoma of the skin (BCC) is the most common malignant neoplasm in humans. BCC is primarily driven by the aberrant activation of the Sonic Hedgehog (Hh) pathway. However, its extensive phenotypical variation remains to be explained. The genetic profiling of 293 BCCs revealed the highest mutation rate observed in cancer (65 Mutations/Mb), with strong prevalence of UV-light signature mutations. 85% of BCCs harbored mutations in Hh pathway genes: mutually exclusive PTCH1 (73%) and SMO (20%) (P=6.6x10-8), SUFU (8%), and in TP53 (61%). 85% of BCCs also harbored secondary driver mutations in other genes implicated in BCC tumorigenesis. Recurrent secondary driver mutations were observed in MYCN (30%), PPP6C (15%), STK19 (10%), LATS1 (8%), ERBB2 (4%), PIK3CA (2%), RAC1 (1%) and N/K/H-RAS (2%). Loss of function (LoF) and deleterious missense mutations were observed in PTPN14 (23%), RB1 (8%) and FBXW7 (5%). In line with the mutational profiles detected by RNAseq, we observed activation of the Hh pathway as well as upregulation of target genes of the Hippo-YAP pathway and activation of MYCN target genes. The functional analysis of the novel tumorigenic driver mutations in MYCN, PTPN14 and LATS1 demonstrates their relevance in BCC tumorigenesis and provides an expanded molecular understanding of BCC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-10-07T12:58:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001541","title":"CRISPR_SAM_screens","description":"CRSPR SAM libraries will be used in cancer cell lines to identify resistance mechanisms to anti-cancer drugs. Cancer cell lines will be given a whole-genome libraries, in order to create a frmaeshifts in the cell population. After cells will be exposed to anti-cancer drugs and resistant cells will be collected for DNA extractions and future sequencing. Amplicons containing gRNA sequences will be amplified , librarie will be created with different tags for Illumina sequencing.","abstract":"Overexpression of genes is a quite common event during cancer progression and is a one of ther reason for anti cancer drug resistance. Here we are going to use activation CRISPR SAM library in order to overexpress whole genome, 1 gene per cell. Like this we will generate a population of cells  with 1 amplified gene per cell. The treatment with different anti-cancer drugs will kill the majrity of cells, and only thouse that have  drug resistnt overexpression will survive.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001542","title":"Whole exome sequencing of germline DNA was performed and subsequent polymorphisms in genes known and putatively involved in the innate immune response to fungi were identified","description":"Disease can be conceptualized as the result of interactions between infecting microbe and holobiont, the combination of a host and its microbial communities. It is likely that genomic variation in the host, infecting microbe, and commensal microbiota are key determinants of infectious disease clinical outcomes. However, until recently, simultaneous, multiomic investigation of infecting microbe and holobiont components has rarely been explored. Herein, we characterized the infecting microbe, host, micro- and mycobiomes leading up to infection onset in a leukemia patient that developed invasive mucormycosis. We discovered that the patient was infected with a strain of the recently described Mucor velutinosus species which we determined was hypervirulent in a Drosophila challenge model and has a predisposition for skin dissemination. After completing the infecting M. velutinosus genome and genomes from four other Mucor species, comparative pathogenomics was performed and assisted in identifying 66 M. velutinosus-specific putatively secreted proteins, including multiple novel secreted aspartyl proteinases which may contribute to the unique clinical presentation of skin dissemination. Whole exome sequencing of the patient revealed multiple non-synonymous polymorphisms in genes critical to control of fungal proliferation, such as TLR6 and PTX3. Moreover, the patient had a non-synonymous polymorphism in the NOD2 gene and a missense mutation in FUT2, which have been linked to microbial dysbiosis and microbiome diversity maintenance during physiologic stress, respectively. In concert with host genetic polymorphism data, the micro- and mycobiome analyses revealed that the infection developed amid a dysbiotic microbiome with low α-diversity, dominated by staphylococci. Additionally, longitudinal mycobiome data showed that M. velutinosus DNA was detectable in oral samples preceding disease onset. Our genome-level study of the host-infecting microbe-commensal triad extends the concept of personalized genomic medicine to the holobiont-infecting microbe interface thereby offering novel opportunities for using synergistic genetic methods to increase understanding of infectious diseases pathogenesis and clinical outcomes.","abstract":"Disease can be conceptualized as the result of interactions between infecting microbe and holobiont, the combination of a host and its microbial communities. It is likely that genomic variation in the host, infecting microbe, and commensal microbiota are key determinants of infectious disease clinical outcomes. However, until recently, simultaneous, multiomic investigation of infecting microbe and holobiont components has rarely been explored. Herein, we characterized the infecting microbe, host, micro- and mycobiomes leading up to infection onset in a leukemia patient that developed invasive mucormycosis. We discovered that the patient was infected with a strain of the recently described Mucor velutinosus species which we determined was hypervirulent in a Drosophila challenge model and has a predisposition for skin dissemination. After completing the infecting M. velutinosus genome and genomes from four other Mucor species, comparative pathogenomics was performed and assisted in identifying 66 M. velutinosus-specific putatively secreted proteins, including multiple novel secreted aspartyl proteinases which may contribute to the unique clinical presentation of skin dissemination. Whole exome sequencing of the patient revealed multiple non-synonymous polymorphisms in genes critical to control of fungal proliferation, such as TLR6 and PTX3. Moreover, the patient had a non-synonymous polymorphism in the NOD2 gene and a missense mutation in FUT2, which have been linked to microbial dysbiosis and microbiome diversity maintenance during physiologic stress, respectively. In concert with host genetic polymorphism data, the micro- and mycobiome analyses revealed that the infection developed amid a dysbiotic microbiome with low α-diversity, dominated by staphylococci. Additionally, longitudinal mycobiome data showed that M. velutinosus DNA was detectable in oral samples preceding disease onset. Our genome-level study of the host-infecting microbe-commensal triad extends the concept of personalized genomic medicine to the holobiont-infecting microbe interface thereby offering novel opportunities for using synergistic genetic methods to increase understanding of infectious diseases pathogenesis and clinical outcomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-10-07T21:03:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001543","title":"Thu_Oct_08_14_06_38_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001544","title":"Thu_Oct_08_14_07_32_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001545","title":"Thu_Oct_08_14_07_36_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001546","title":"Thu_Oct_08_14_13_14_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001547","title":"Thu_Oct_08_14_14_05_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001548","title":"Thu_Oct_08_14_14_09_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001549","title":"Thu_Oct_08_14_22_41_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001550","title":"Thu_Oct_08_14_23_32_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001551","title":"Thu_Oct_08_14_23_36_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001552","title":"Whole genome sequencing of primary and metastatic Melanoma cases in an Australian cohort.","description":"Melanoma is the fourth most common cancer in Australia and the leading\ncause of cancer death in young adults. The Australian Melanoma Genome\nProject (AMGP) is analysing whole genomes from melanomas. We include the results of whole\ngenome sequencing (WGS) for a number of datasets that include cutaneous, acral and mucosal melanoma subtypes.","abstract":"Melanoma is the fourth most common cancer in Australia and the leading\ncause of cancer death in young adults. The Australian Melanoma Genome\nProject (AMGP) is analysing whole genomes from melanomas. We include the results of whole\ngenome sequencing (WGS) for a number of datasets that include cutaneous, acral and mucosal melanoma subtypes.","study_type":"Other","pubmed_ids":[28467829],"external_links":null,"is_released":true,"released_date":"2015-10-09T07:29:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001553","title":"Genetic landscape of relapsed DLBCL","description":"Diffuse large B-cell lymphoma is a heterogenous malignancy that can arise de novo or can result from histologic transformation from indolent lymphomas. Considerable sequencing effort has been placed on determining the mutations that are common at the time of diagnosis in DLBCL but little is known about the nature of relapsed disease. We have sequenced tumour and matched normal exomes of 38 rrDLBCL patients including 25 de novo DLBCLs and 13 transformed lymphomas to identify somatic mutations and copy number alterations associated with relapse.","abstract":"Diffuse large B-cell lymphoma is a heterogenous malignancy that can arise de novo or can result from histologic transformation from indolent lymphomas. Considerable sequencing effort has been placed on determining the mutations that are common at the time of diagnosis in DLBCL but little is known about the nature of relapsed disease. We have sequenced tumour and matched normal exomes of 38 rrDLBCL patients including 25 de novo DLBCLs and 13 transformed lymphomas to identify somatic mutations and copy number alterations associated with relapse.","study_type":"Other","pubmed_ids":[26647218],"external_links":null,"is_released":true,"released_date":"2015-10-10T00:37:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001554","title":"Mon_Oct_12_09_25_50_BST_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001555","title":"Mon_Oct_12_09_26_44_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001556","title":"Mon_Oct_12_09_26_48_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001557","title":"Evolutionary_conservation_of_Th2_differentiation_between_human_and_mouse_____","description":"Naïve CD4+ T cells can differentiate into various lineages of helper and regulatory T cells. One of those lineages is T helper 2 cells (Th2), which are important and required for humoral immunity and the response to large extracellular pathogens. Transcription factors can decode the genomic information encoded in the regulatory elements, such as promoters and enhancers, which are important for the cellular differentiation process. In this study, we are using recent epigenetic techniques, including ChIP-seq and ATAC-seq, to investigate the conservation of the differentiation process of Th2 between human and \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Naïve CD4+ T cells can differentiate into various lineages of helper and regulatory T cells. One of those lineages is T helper 2 cells (Th2), which are important and required for humoral immunity and the response to large extracellular pathogens. Transcription factors can decode the genomic information encoded in the regulatory elements, such as promoters and enhancers, which are important for the cellular differentiation process. In this study, we are using recent epigenetic techniques, including ChIP-seq and ATAC-seq, to investigate the conservation of the differentiation process of Th2 between human and mouse.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001558","title":"APCDR Uganda GWAS: Genome-wide sequence variation and susceptibility loci for cardiometabolic traits in a sub-Saharan African population (UGWAS component)","description":"Genomic studies in African populations provide unique opportunities to understand disease aetiology, human genetic diversity and population history in a regional and a global context. To leverage the relative benefits of different strategies, we undertook a combined approach of genotyping and whole-genome sequencing (WGS) in a population-based study of 6,400 individuals from a geographically defined rural community in South-West Uganda. We present data from 4,778 individuals with genotypes for ~2.2 million SNPs from the Uganda GWAS resource (UGWAS), and sequence data on up to 1,978 individuals spanning 41.5M SNPs and 4.5M indels (UG2G); 343 individuals overlap between the two datasets. \nWe highlight the value of the largest sequence panel from Africa to date as a global resource for variant discovery, imputation and understanding the mutational spectrum and its clinical relevance in African populations. Alongside phenotype data, we provide a rich new genomic resource for researchers in Africa and globally.","abstract":"Genomic studies in African populations provide unique opportunities to understand disease aetiology, human genetic diversity and population history in a regional and a global context. To leverage the relative benefits of different strategies, we undertook a combined approach of genotyping and whole-genome sequencing (WGS) in a population-based study of 6,400 individuals from a geographically defined rural community in South-West Uganda. We present data from 4,778 individuals with genotypes for ~2.2 million SNPs from the Uganda GWAS resource (UGWAS), and sequence data on up to 1,978 individuals spanning 41.5M SNPs and 4.5M indels (UG2G); 343 individuals overlap between the two datasets. \nWe highlight the value of the largest sequence panel from Africa to date as a global resource for variant discovery, imputation and understanding the mutational spectrum and its clinical relevance in African populations. Alongside phenotype data, we provide a rich new genomic resource for researchers in Africa and globally.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-10-12T15:08:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001559","title":"AML_WES","description":"This 2014_AML_WES study includes 40 paired samples derived from Korean AML paitients.\nAML Bone Marrow samples were collected and paired with each normal(Saliva or BM derived) sequencing data.\nThe results of this CN study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.","abstract":"This 2014_AML_WES study includes 40 paired samples derived from Korean AML paitients.\nAML Bone Marrow samples were collected and paired with each normal(Saliva or BM derived) sequencing data.\nThe results of this CN study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-10-14T12:14:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001560","title":"ESCC project hold by ZZUFHECRKL","description":"Whole-genome sequencing in 60 cases and whole-exome sequencing in 146 cases of Chinese ESCC","abstract":"Whole-genome sequencing in 60 cases and whole-exome sequencing in 146 cases of Chinese ESCC","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001561","title":"PSCP_mutation_analysis_in_hESCs","description":"Many studies over the past 10 years, culminating in the recent report of the International Stem Cell Initiative (ISCI, 2011) have shown that hPSC acquire genetic and epigenetic changes during their time in culture. Many of the genetic changes are non-random and recurrent, probably because they provide a selective growth advantage to the undifferentiated cells. Some are shared by embryonal carcinoma cells, the malignant counterparts of ES cells. The origins of these growth advantages are poorly understood, but may come from altered cell cycle dynamics, resistance to apoptosis or altered patterns of differentiation. Less is known about the nature and consequences of epigenetic changes, but it is likely that these similarly affect hPSC behaviour; e.g., enhanced expression of DLK1, an imprinted gene, is associated with altered hPSC growth (Enver et al 2005). Inevitably, these genetic and epigenetic changes will impact on our ability to use hPSC for regenerative medicine, either because malignant transformation of the undifferentiated cells or their differentiated derivatives to be used for transplantation compromises safety, or because they impede the function of those differentiated derivatives, or because they affect the efficiency with which the undifferentiated cells can be expanded and differentiated into desired cell types. Focusing initially upon the existing clinical grade hESC lines, later moving to iPSC, we will Consolidate and extend knowledge of the rate, type and functional impact of the genetic variations that occur during hPSC culture. We will use whole genome and exome sequencing as well as SNP arrays, together with clonal analysis and other cytogenetics techniques. Common changes will be compared with those found in the normal human population, at low frequency in the original cell population or observed during iPSC generation in the HIPSCI project currently based at the WTSI. These studies will provide a better understanding of the range of genetic changes that occur in hPSC beyond the CNVs already identified. In conjunction with cancer genome resources and expertise at WTSI, bioinformatic analyses of these hPSC data will allow us to assess potential impact on hPSC behaviour pertinent to applications in regenerative medicine, notably the likelihood that specific changes arising in undifferentiated PSC cultures may be associated with potential malignant transformation of differentiated progeny. This data is part of a pre-publication release. For information on the proper use of pre-publication data shred by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The goal of this study is to analyse a total of 80 subcloned hESC lines, which are derived from 2 MasterShef ESC lines by whole genome sequencing. After this initial study, additional pluripotent stem cell lines may be analysed.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-10-16T07:35:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001562","title":"Fri_Oct_16_14_14_07_BST_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001563","title":"Genomic characterization of Malignant Pleural Mesothelioma.","description":"Genomic characterization of Malignant Pleural Mesothelioma using RNA-seq, Exome and Illumina 2.5 M array.","abstract":"Genomic characterization of Malignant Pleural Mesothelioma using RNA-seq, Exome and Illumina 2.5 M array.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-10-16T19:16:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001564","title":"Immunoseq first paper","description":"Background: Comprehensive DNase I hypersensitive site (DHS) mapping by the ENCODE and NIH Roadmap Epigenomics projects has identified many classes of cis-regulatory elements. Studies have shown an enrichment of complex trait GWAS hits in these DHS regions. However, given that most of these loci are in non-coding DNA, their genetic makeup remains largely unexplored, as most recent studies of complex traits have been restricted to whole-exome sequencing. The discovery of rare non-coding variants located in regulatory regions that are specific to immune cells should further explain their role in complex traits. Results: We designed a custom capture panel to identify and assess the impact of rare non-coding variation in immune and chronic inflammatory diseases. Our approach combines selective DNA capture of relevant regulatory regions with next-generation sequencing. Genome-wide DHS mapping data from the ENCODE and NIH Roadmap Epigenomics projects was used to locate the regulatory regions of immune cells. We first applied the “Immunoseq” assay to 30 healthy individuals where we had existing transcriptome data from T cells. Using Immunoseq, we identified a large number of novel non-coding variants in these samples. Relying on allele specific expression measurements, we also showed that our selected capture regions are enriched for functional variants that have an impact on differential allelic gene expression. The results from a replication set with 180 samples confirmed our observations. Conclusions: We show that the Immunoseq is a powerful approach to detect novel rare variants in regulatory regions. We also demonstrate that these novel variants have a potential functional role in immune cells.","abstract":"Background: Comprehensive DNase I hypersensitive site (DHS) mapping by the ENCODE and NIH Roadmap Epigenomics projects has identified many classes of cis-regulatory elements. Studies have shown an enrichment of complex trait GWAS hits in these DHS regions. However, given that most of these loci are in non-coding DNA, their genetic makeup remains largely unexplored, as most recent studies of complex traits have been restricted to whole-exome sequencing. The discovery of rare non-coding variants located in regulatory regions that are specific to immune cells should further explain their role in complex traits. Results: We designed a custom capture panel to identify and assess the impact of rare non-coding variation in immune and chronic inflammatory diseases. Our approach combines selective DNA capture of relevant regulatory regions with next-generation sequencing. Genome-wide DHS mapping data from the ENCODE and NIH Roadmap Epigenomics projects was used to locate the regulatory regions of immune cells. We first applied the “Immunoseq” assay to 30 healthy individuals where we had existing transcriptome data from T cells. Using Immunoseq, we identified a large number of novel non-coding variants in these samples. Relying on allele specific expression measurements, we also showed that our selected capture regions are enriched for functional variants that have an impact on differential allelic gene expression. The results from a replication set with 180 samples confirmed our observations. Conclusions: We show that the Immunoseq is a powerful approach to detect novel rare variants in regulatory regions. We also demonstrate that these novel variants have a potential functional role in immune cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001565","title":"The_British_Autozygosity_Populations_BioResource","description":"This data set contains whole exome sequences of 500 individuals with self-stated parental\nrelatedness from the East London Genes &amp; Health cohort. Rare frequency functional variants\nin these healthy individuals will be studied with respect to the genetic health of the\nparticipants and loss-of-function analysis of human genes.","abstract":"This data set contains whole exome sequences of 500 individuals with self-stated parental\nrelatedness from the East London Genes &amp; Health cohort. Rare frequency functional variants\nin these healthy individuals will be studied with respect to the genetic health of the\nparticipants and loss-of-function analysis of human genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-10-19T12:10:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001566","title":"Functional sequence variants identified by Immunoseq target capture and sequencing of active regions in human immune cells","description":"Background: Comprehensive DNase I hypersensitive site (DHS) mapping by the ENCODE and NIH Roadmap Epigenomics projects has identified many classes of cis-regulatory elements. Studies have shown an enrichment of complex trait GWAS hits in these DHS regions. However, given that most of these loci are in non-coding DNA, their genetic makeup remains largely unexplored, as most recent studies of complex traits have been restricted to whole-exome sequencing. The discovery of rare non-coding variants located in regulatory regions that are specific to immune cells should further explain their role in complex traits. Results: We designed a custom capture panel to identify and assess the impact of rare non-coding variation in immune and chronic inflammatory diseases. Our approach combines selective DNA capture of relevant regulatory regions with next-generation sequencing. Genome-wide DHS mapping data from the ENCODE and NIH Roadmap Epigenomics projects was used to locate the regulatory regions of immune cells. We first applied the “Immunoseq” assay to 30 healthy individuals where we had existing transcriptome data from T cells. Using Immunoseq, we identified a large number of novel non-coding variants in these samples. Relying on allele specific expression measurements, we also showed that our selected capture regions are enriched for functional variants that have an impact on differential allelic gene expression. The results from a replication set with 180 samples confirmed our observations. Conclusions: We show that the Immunoseq is a powerful approach to detect novel rare variants in regulatory regions. We also demonstrate that these novel variants have a potential functional role in immune cells.","abstract":"Background: Comprehensive DNase I hypersensitive site (DHS) mapping by the ENCODE and NIH Roadmap Epigenomics projects has identified many classes of cis-regulatory elements. Studies have shown an enrichment of complex trait GWAS hits in these DHS regions. However, given that most of these loci are in non-coding DNA, their genetic makeup remains largely unexplored, as most recent studies of complex traits have been restricted to whole-exome sequencing. The discovery of rare non-coding variants located in regulatory regions that are specific to immune cells should further explain their role in complex traits. Results: We designed a custom capture panel to identify and assess the impact of rare non-coding variation in immune and chronic inflammatory diseases. Our approach combines selective DNA capture of relevant regulatory regions with next-generation sequencing. Genome-wide DHS mapping data from the ENCODE and NIH Roadmap Epigenomics projects was used to locate the regulatory regions of immune cells. We first applied the “Immunoseq” assay to 30 healthy individuals where we had existing transcriptome data from T cells. Using Immunoseq, we identified a large number of novel non-coding variants in these samples. Relying on allele specific expression measurements, we also showed that our selected capture regions are enriched for functional variants that have an impact on differential allelic gene expression. The results from a replication set with 180 samples confirmed our observations. Conclusions: We show that the Immunoseq is a powerful approach to detect novel rare variants in regulatory regions. We also demonstrate that these novel variants have a potential functional role in immune cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001567","title":"Imprinting of skin/inflammation-homing in CD4+ T cells is controlled by DNA methylation within the fucosyltransferase 7 gene","description":"CD4+ effector/memory cells use E- and P-selectin ligands (E- and P-ligs) for homing to the skin and acute inflamed regions, whereas α4β7 and CCR9 promote homing into the gut. Retinoic acid (RA) is a key inducer of gut-homing while concomitantly suppressing skin homing. In this study, we found that high expression of fucosyltransferase 7 (fut7), the enzyme crucial for generation of the glycosylated E- and P-ligs in T cells, correlates with DNA demethylation within a minimal promoter of the fut7 gene in skin/inflammation-seeking effector/memory T cells. RA abrogated the activation-induced demethylation of this region, which contains a cAMP responsive element (CRE) sequence. Methylation of the promoter or mutation of the CRE binding site abolished promoter activity confirming the importance of this region and of its demethylation for fut7 transcriptional activity in T cells. Furthermore, human CD4+ effector/memory T cells showed intragenic demethylation corresponding to high Fut7 expression, while non-hematopoetic cells – lacking selectin ligand expression – such as hepatocytes, exhibit extensive methylation of the fut7 gene. In conclusion, we show that the topographic commitment of T cells for skin and inflammation is imprinted by DNA demethylation within a minimal promoter of the fut7 gene that is conserved across human and mouse.","abstract":"CD4+ effector/memory cells use E- and P-selectin ligands (E- and P-ligs) for homing to the skin and acute inflamed regions, whereas α4β7 and CCR9 promote homing into the gut. Retinoic acid (RA) is a key inducer of gut-homing while concomitantly suppressing skin homing. In this study, we found that high expression of fucosyltransferase 7 (fut7), the enzyme crucial for generation of the glycosylated E- and P-ligs in T cells, correlates with DNA demethylation within a minimal promoter of the fut7 gene in skin/inflammation-seeking effector/memory T cells. RA abrogated the activation-induced demethylation of this region, which contains a cAMP responsive element (CRE) sequence. Methylation of the promoter or mutation of the CRE binding site abolished promoter activity confirming the importance of this region and of its demethylation for fut7 transcriptional activity in T cells. Furthermore, human CD4+ effector/memory T cells showed intragenic demethylation corresponding to high Fut7 expression, while non-hematopoetic cells – lacking selectin ligand expression – such as hepatocytes, exhibit extensive methylation of the fut7 gene. In conclusion, we show that the topographic commitment of T cells for skin and inflammation is imprinted by DNA demethylation within a minimal promoter of the fut7 gene that is conserved across human and mouse.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001568","title":"reChIP-seq reveals widespread bivalency of H3K4me3 and H3K27me3 in CD4+ memory T-Cells","description":"Identification of genomic loci exhibiting the physical co-localization of two distinct DNA-associated proteins remains a technical challenge. To tackle this challenge we have developed a novel reChIP-seq approach that enriches for two distinct DNA-associated proteins in an unbiased and genome-wide manner. We illustrate the utility of our approach by identifying nucleosomes bivalently modified by H3K4me3 and H3K27me3 in primary human CD4+ central memory T-cells (TCMs). We unravel widespread bivalency of many unmethylated CpG-rich regions in TCMs overlapping with transcriptional start sites of developmental regulators. Furthermore, reChIP-seq uncovers two yet unobserved classes of bivalency, where either H3K4me3 or H3K27me3 is mixed with low but detectable bivalency. We provide evidence that bivalency is established by an interplay between genome and epigenome and thus attains stability. Our described reChIP-seq approach augments conventional ChIP-seq and is broadly applicable in the study of co-localization of DNA-associated proteins to unravel the intricate possibilities of combinatorial action.","abstract":"Identification of genomic loci exhibiting the physical co-localization of two distinct DNA-associated proteins remains a technical challenge. To tackle this challenge we have developed a novel reChIP-seq approach that enriches for two distinct DNA-associated proteins in an unbiased and genome-wide manner. We illustrate the utility of our approach by identifying nucleosomes bivalently modified by H3K4me3 and H3K27me3 in primary human CD4+ central memory T-cells (TCMs). We unravel widespread bivalency of many unmethylated CpG-rich regions in TCMs overlapping with transcriptional start sites of developmental regulators. Furthermore, reChIP-seq uncovers two yet unobserved classes of bivalency, where either H3K4me3 or H3K27me3 is mixed with low but detectable bivalency. We provide evidence that bivalency is established by an interplay between genome and epigenome and thus attains stability. Our described reChIP-seq approach augments conventional ChIP-seq and is broadly applicable in the study of co-localization of DNA-associated proteins to unravel the intricate possibilities of combinatorial action.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-10-20T14:43:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001569","title":"Population whole-genome bisulfite sequencing across two tissues highlights environment as principal source of human methylome variation","description":"The study includes whole-genome bisulfite sequencing (WGBS) on 34 adipose(7 MZ pairs, 6 DZ pairs and 8 singletons) and 27 blood (7 MZ pairs, 6 DZpairs and 1 singleton) DNA samples derived from a total of 43 female twinsbelonging to the MuTHER/TwinsUK cohort. We generated 11.5 billion 100bppaired-end reads covering 2.3 Tera-basepairs (Tbp) ofsequence using the Illumina HiSeq2000 or 2500 systems. Applying standardalignment methods and filters we obtain a mean genome coverage of 6.3-fold(range: 1.0- to 12.9-fold) for adipose and 8.7-fold (range: 0.7- to29.0-fold) for blood.","abstract":"The study includes whole-genome bisulfite sequencing (WGBS) on 34 adipose(7 MZ pairs, 6 DZ pairs and 8 singletons) and 27 blood (7 MZ pairs, 6 DZpairs and 1 singleton) DNA samples derived from a total of 43 female twinsbelonging to the MuTHER/TwinsUK cohort. We generated 11.5 billion 100bppaired-end reads covering 2.3 Tera-basepairs (Tbp) ofsequence using the Illumina HiSeq2000 or 2500 systems. Applying standardalignment methods and filters we obtain a mean genome coverage of 6.3-fold(range: 1.0- to 12.9-fold) for adipose and 8.7-fold (range: 0.7- to29.0-fold) for blood.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-10-23T19:47:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001570","title":"Data from the paper Context-specific Effects of TGFβ/SMAD3 in Cancer Are Modulated by the Epigenome. Tufegdzic et al, Cell Reports 2015","description":"The transforming growth factor beta (TGFβ) signalling pathway exerts opposing effects on cancer cells, acting either as a tumor-promoter or as a tumor-suppressor. Here we show these opposing effects are a result of the synergy between SMAD3, a downstream effector of TGFβ signalling, and the distinct epigenomes of breast tumor initiating cells (BTICs). These effects of TGFβ are associated with distinct gene expression programs, but genomic SMAD3 binding patterns are highly similar in the BTIC-promoting and BTIC- suppressing contexts. Our data show cell type-specific epigenetic configurations provide a modulatory layer by determining accessibility of genes to regulation by TGFβ/SMAD3. LBH, one such context-specific target gene, is regulated according to its DNA methylation status, and is crucial for TGFβ-dependent promotion of BTICs. Overall, these results reveal that the epigenome plays a central and previously overlooked role in shaping the context-specific effects of TGFβ in cancer.","abstract":"The transforming growth factor beta (TGFβ) signalling pathway exerts opposing effects on cancer cells, acting either as a tumor-promoter or as a tumor-suppressor. Here we show these opposing effects are a result of the synergy between SMAD3, a downstream effector of TGFβ signalling, and the distinct epigenomes of breast tumor initiating cells (BTICs). These effects of TGFβ are associated with distinct gene expression programs, but genomic SMAD3 binding patterns are highly similar in the BTIC-promoting and BTIC- suppressing contexts. Our data show cell type-specific epigenetic configurations provide a modulatory layer by determining accessibility of genes to regulation by TGFβ/SMAD3. LBH, one such context-specific target gene, is regulated according to its DNA methylation status, and is crucial for TGFβ-dependent promotion of BTICs. Overall, these results reveal that the epigenome plays a central and previously overlooked role in shaping the context-specific effects of TGFβ in cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-10-24T00:04:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001571","title":"Whole-genome sequencing in 14  cases and whole-exome sequencing in 90 cases of Chinese ESCC","description":"Esophageal cancer is one of the most aggressive cancers and the sixth leading cause of cancer death worldwide1. Approximately 70% of the global esophageal cancers occur in China and over 90% histopathological forms of this disease are esophageal squamous cell carcinoma (ESCC)2-3. Currently, there are limited clinical approaches for early diagnosis and treatment for ESCC, resulting in a 10% 5-year survival rate for the patients. Meanwhile, the full repertoire of genomic events leading to the pathogenesis of ESCC remains unclear. Here we show a comprehensive genomic analysis in 158 ESCC cases, as part of the International Cancer Genome Consortium (ICGC) Research Projects (http://icgc.org/icgc/cgp/72/371/1001734). We conducted whole-genome sequencing in 14 ESCC cases and whole-exome sequencing in 90 cases.","abstract":"Esophageal cancer is one of the most aggressive cancers and the sixth leading cause of cancer death worldwide1. Approximately 70% of the global esophageal cancers occur in China and over 90% histopathological forms of this disease are esophageal squamous cell carcinoma (ESCC)2-3. Currently, there are limited clinical approaches for early diagnosis and treatment for ESCC, resulting in a 10% 5-year survival rate for the patients. Meanwhile, the full repertoire of genomic events leading to the pathogenesis of ESCC remains unclear. Here we show a comprehensive genomic analysis in 158 ESCC cases, as part of the International Cancer Genome Consortium (ICGC) Research Projects (http://icgc.org/icgc/cgp/72/371/1001734). We conducted whole-genome sequencing in 14 ESCC cases and whole-exome sequencing in 90 cases.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001572","title":"Distinct portrayal of lesions in synchronous multifocal lung adenocarcinoma revealed by genome sequencing","description":"Distinguishing multiple primary lung cancers in the synchronous multifocal intrapulmonary lesions has important significance on clinical staging and therapeutic decision. To investigate genomic aberration profiles, we applied whole genome and whole exome sequencing, and microarray-based comparative genomic hybridization on 15 intrapulmonary tumors derived from six patients with synchronous multifocal lung cancers having similar histological diagnosis. Any pair of intrapulmonary tumors in a single patient, which shared the identical genetic background and environment, showed an extinctive heterogeneity between each other. Phylogenetic relationship analysis indicated an independently branched evolution among all the tumors, suggesting they were multiple primary lung cancers. EGFR or KRAS mutations were found in 7 or 3 out of the 15 tumors, from 3 or 2 patients, respectively. Somatic mutational heterogeneity of these two genes in a single patient was also observed.  Our analysis indicates genomic aberration profiling is valuable for identification of multiple primary lung cancer, especially when high histopathological concordance was observed between lesions.  We also suggest a thoroughly molecular diagnosis against therapeutic target genes should be taken for each accessible nodule before making a plan for adjuvant therapy.","abstract":"Distinguishing multiple primary lung cancers in the synchronous multifocal intrapulmonary lesions has important significance on clinical staging and therapeutic decision. To investigate genomic aberration profiles, we applied whole genome and whole exome sequencing, and microarray-based comparative genomic hybridization on 15 intrapulmonary tumors derived from six patients with synchronous multifocal lung cancers having similar histological diagnosis. Any pair of intrapulmonary tumors in a single patient, which shared the identical genetic background and environment, showed an extinctive heterogeneity between each other. Phylogenetic relationship analysis indicated an independently branched evolution among all the tumors, suggesting they were multiple primary lung cancers. EGFR or KRAS mutations were found in 7 or 3 out of the 15 tumors, from 3 or 2 patients, respectively. Somatic mutational heterogeneity of these two genes in a single patient was also observed.  Our analysis indicates genomic aberration profiling is valuable for identification of multiple primary lung cancer, especially when high histopathological concordance was observed between lesions.  We also suggest a thoroughly molecular diagnosis against therapeutic target genes should be taken for each accessible nodule before making a plan for adjuvant therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-10-28T07:05:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001573","title":"The_genetic_evolution_of_precursor_lesions_in_pancreatic_cancer","description":"Mapping genetic evolution of pancreatic cancer precursor lesions such as IPMNs and PanINs.","abstract":"This study aims to map the genetic evolution of precursor lesions such as IPMNs (intraductal papillary mucinous neoplasms) and PanINs (pancreatic intraepithelial neoplasias) into invasive pancreatic cancer via next generation sequencing analysis of cyst fluid and resected pancreatic specimens within the Pancreatic Tissue Biobank. Three groups of specimens will be identified; specifically those containing 1)various grades of IPMN, 2)IPMN with adjacent cancer and 3)PanIN with adjacent cancer. Individual lesions within these specimens will be microdissected out with laser capture microdissection (prior to submitting to WTSI) and genomic DNA extracted (at the WTSI) from each individual tissue sample as well as cyst fluid. Next generation sequencing will be performed at the WTSI on these samples to identify differences in the genetic profiles of these lesions as they progress from the pre-malignant stage to malignancy.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-10-29T09:26:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001574","title":"Seeking the driver in tumours with apparent normal molecular profile on Comparative Genomic Hybridization and targeted gene panel sequencing: What is the added value of whole exome sequencing?","description":"Background Molecular tumour profiling technologies have become increasingly important in the era of precision medicine, but their routine use is limited by their accessibility, cost, and tumour material availability. It is therefore crucial to assess their relative added value to optimise the sequence and combination of such technologies.  Patients and methods Within the MOSCATO-01 trial, we investigated the added value of whole exome sequencing (WES) in patients that did not present any molecular abnormality on array comparative genomic hybridisation (aCGH) and targeted gene panel sequencing (TGPS) using cancer specific panels. The pathogenicity potential and actionability of mutations detected on WES was assessed.  A publication is pending association with this study.","abstract":"Background Molecular tumour profiling technologies have become increasingly important in the era of precision medicine, but their routine use is limited by their accessibility, cost, and tumour material availability. It is therefore crucial to assess their relative added value to optimise the sequence and combination of such technologies.  Patients and methods Within the MOSCATO-01 trial, we investigated the added value of whole exome sequencing (WES) in patients that did not present any molecular abnormality on array comparative genomic hybridisation (aCGH) and targeted gene panel sequencing (TGPS) using cancer specific panels. The pathogenicity potential and actionability of mutations detected on WES was assessed.  A publication is pending association with this study.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001575","title":"Prenatal lead exposure is associated with decreased cord blood DNA methylation of the glycoprotein VI gene involved in platelet activation and thrombus formation","description":"Early-life lead exposure impairs neurodevelopment and later exposure affects the cardiovascular system. Lead has been associated with reduced global 5-methylcytosine DNA methylation, suggesting that lead toxicity acts through epigenetic mechanisms. The objective of this study is to clarify how early life lead exposure alters DNA methylation of specific genes, using an epigenomic approach. We measured lead concentrations in urine (gestational week, GW, 8) and erythrocytes (GW 14), using ICP-MS, for 127 pregnant mothers recruited in the MINIMat food and supplementation cohort in rural Bangladesh. Cord blood DNA methylation was analyzed with the Infinium HumanMethylation450K BeadChip and top sites were validated by methylation-sensitive high-resolution melt curve analysis. Maternal urinary lead concentrations (divided into quartiles) showed significant (after adjustment for FDR) inverse associations with methylation at nine CpGs. Three of these sites were in the 5’ end, including the promoter, of glycoprotein IV (GP6); cg18355337 (q=0.029, β=-0.30), cg25818583 (q=0.041, β=-0.18) and cg23796967 (q=0.047, β=-0.17). The methylation in another CpG site in GP6 was close to significant (cg05374025, q=0.057, β=-0.23). The erythrocyte lead concentrations (divided into quartiles) were also inversely associated with CpG methylation in GP6, although this was not statistically significant after FDR-adjustments. Eight CpG sites in GP6 constituted a differentially methylated region in relation to urinary lead (p=0.005, q=0.48) and erythrocyte lead (p=0.007, q=0.46). In conclusion, we found that moderate prenatal lead exposure appear to epigenetically affect GP6, a key component of platelet aggregation and thrombus formation, suggesting a novel link between early lead exposure and cardiovascular disease later in life.","abstract":"Early-life lead exposure impairs neurodevelopment and later exposure affects the cardiovascular system. Lead has been associated with reduced global 5-methylcytosine DNA methylation, suggesting that lead toxicity acts through epigenetic mechanisms. The objective of this study is to clarify how early life lead exposure alters DNA methylation of specific genes, using an epigenomic approach. We measured lead concentrations in urine (gestational week, GW, 8) and erythrocytes (GW 14), using ICP-MS, for 127 pregnant mothers recruited in the MINIMat food and supplementation cohort in rural Bangladesh. Cord blood DNA methylation was analyzed with the Infinium HumanMethylation450K BeadChip and top sites were validated by methylation-sensitive high-resolution melt curve analysis. Maternal urinary lead concentrations (divided into quartiles) showed significant (after adjustment for FDR) inverse associations with methylation at nine CpGs. Three of these sites were in the 5’ end, including the promoter, of glycoprotein IV (GP6); cg18355337 (q=0.029, β=-0.30), cg25818583 (q=0.041, β=-0.18) and cg23796967 (q=0.047, β=-0.17). The methylation in another CpG site in GP6 was close to significant (cg05374025, q=0.057, β=-0.23). The erythrocyte lead concentrations (divided into quartiles) were also inversely associated with CpG methylation in GP6, although this was not statistically significant after FDR-adjustments. Eight CpG sites in GP6 constituted a differentially methylated region in relation to urinary lead (p=0.005, q=0.48) and erythrocyte lead (p=0.007, q=0.46). In conclusion, we found that moderate prenatal lead exposure appear to epigenetically affect GP6, a key component of platelet aggregation and thrombus formation, suggesting a novel link between early lead exposure and cardiovascular disease later in life.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-10-30T14:06:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001576","title":"Mon_Nov_02_09_28_39_GMT_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001577","title":"Mon_Nov_02_09_29_23_GMT_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001578","title":"Mon_Nov_02_09_29_26_GMT_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001579","title":"Mon_Nov_02_09_44_56_GMT_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001580","title":"Mon_Nov_02_09_45_39_GMT_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001581","title":"Mon_Nov_02_09_45_42_GMT_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001582","title":"Mon_Nov_02_09_58_15_GMT_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001583","title":"Mon_Nov_02_09_59_11_GMT_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001584","title":"Mon_Nov_02_09_59_14_GMT_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001585","title":"Genotype and exome data for an Australian Aboriginal population: a reference panel for health-based research","description":"Genetic analyses, including genome-wide association studies and whole exome sequencing (WES), provide powerful tools for the analysis of complex and rare genetic diseases. To date there are no reference data for Aboriginal Australians to underpin the translation of health-based genomic research. Here we provide a catalog of variants called after sequencing the exomes of 72 Aboriginal individuals to a depth of 20X coverage in 80% of the sequenced nucleotides.  We determined 320,976 single nucleotide variants (SNVs) and 47,313 insertions/deletions using the Genome Analysis Toolkit. We had previously genotyped a subset of the Aboriginal individuals (70/72) using the Illumina Omni2.5 BeadChip platform and found 99% concordance at overlapping sites, which suggests high quality genotyping. Finally, we compared our SNVs to six publicly available variant databases, such as dbSNP and the Exome Sequencing Project, and 70,115 of our SNVs did not overlap any of the single nucleotide polymorphic sites in all the databases. Our data set provides a useful reference point for genomic studies on Aboriginal Australians.","abstract":"Genetic analyses, including genome-wide association studies and whole exome sequencing (WES), provide powerful tools for the analysis of complex and rare genetic diseases. To date there are no reference data for Aboriginal Australians to underpin the translation of health-based genomic research. Here we provide a catalog of variants called after sequencing the exomes of 72 Aboriginal individuals to a depth of 20X coverage in 80% of the sequenced nucleotides.  We determined 320,976 single nucleotide variants (SNVs) and 47,313 insertions/deletions using the Genome Analysis Toolkit. We had previously genotyped a subset of the Aboriginal individuals (70/72) using the Illumina Omni2.5 BeadChip platform and found 99% concordance at overlapping sites, which suggests high quality genotyping. Finally, we compared our SNVs to six publicly available variant databases, such as dbSNP and the Exome Sequencing Project, and 70,115 of our SNVs did not overlap any of the single nucleotide polymorphic sites in all the databases. Our data set provides a useful reference point for genomic studies on Aboriginal Australians.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-03T07:07:18+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001586","title":"Multitime and Multisite sequencing analysis of Myeloma","description":"Multiple myeloma is characterised by the abnormal proliferation of aberrant plasma cells in the bone marrow. Patients with multiple myeloma can respond to clinical treatment after diagnosis, but eventually will relapse and develop resistance to treatment. Additionally, myeloma plasma cells can be found in different sites of the bone marrow. We and others have recently demonstrated that myeloma is comprised of different plasma cell subclones, which proportions fluctuate throughout the course of the disease and may vary across different myeloma sites. This study aims to analyse multiple myeloma patients at the time of clinical diagnosis and disease relapse (multitime analysis) as well as different disease sites at the same timepoint (multisite analysis) with the use of whole exome sequencing.","abstract":"Multiple myeloma is characterised by the abnormal proliferation of aberrant plasma cells in the bone marrow. Patients with multiple myeloma can respond to clinical treatment after diagnosis, but eventually will relapse and develop resistance to treatment. Additionally, myeloma plasma cells can be found in different sites of the bone marrow. We and others have recently demonstrated that myeloma is comprised of different plasma cell subclones, which proportions fluctuate throughout the course of the disease and may vary across different myeloma sites. This study aims to analyse multiple myeloma patients at the time of clinical diagnosis and disease relapse (multitime analysis) as well as different disease sites at the same timepoint (multisite analysis) with the use of whole exome sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001587","title":"Papuan_Genotyping","description":"By array based genotyping of indigenous individuals from different areas of Papua New Guinea, this project aims to provide the most comprehensive overview thus far of population structure and history in this part of the world.  Papuans represent a key component in the current understanding of human history outside of Africa. Additionally, PNG harbours enormous cultural and linguistic diversity. Genotyping of diverse individuals, combined with previously generated whole-genome sequencing data, will allow the study of general patterns of population structure, the degree of genetic differentiation between groups, the extent of external gene flow into PNG and the genetic relationships to Australian Aboriginals.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Genotypes of indigenous individuals from different parts of Papua New Guinea (PNG) to provide an overview of the population structure and demographic history in this part of the world.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-03T16:39:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001588","title":"Integrated genomic characterization of IDH1 mutant Glioma malignant progression","description":"Gliomas represent approximately 30% of all central nervous system tumors, and 80% of malignant brain tumors. To understand the molecular mechanisms underlying the malignant progression of low-grade Isocitrate Dehydrogenase 1 (IDH1) mutant gliomas, we studied paired tumor samples from 41 patients, comparing higher-grade, progressed samples to their lower-grade counterparts. Integrated genomic analyses, including whole-exome sequencing, copy number, gene expression and DNA methylation profiling, demonstrated non-linear clonal expansion of the original tumors and identified oncogenic pathways driving progression. These include activation of the MYC and RTK-RAS-PI3K pathways, up-regulation of the FOXM1- and E2F2-mediated cell cycle transition genes, as well as epigenetic silencing of developmental transcriptional factors bound by Polycomb repressive complex 2 in human embryonic stem cells. Our results not only provide mechanistic insight into the genetic and epigenetic mechanisms driving glioma progression but also identify inhibition of the bromodomain and extra-terminal (BET) family as a potential therapeutic approach.","abstract":"Gliomas represent approximately 30% of all central nervous system tumors, and 80% of malignant brain tumors. To understand the molecular mechanisms underlying the malignant progression of low-grade Isocitrate Dehydrogenase 1 (IDH1) mutant gliomas, we studied paired tumor samples from 41 patients, comparing higher-grade, progressed samples to their lower-grade counterparts. Integrated genomic analyses, including whole-exome sequencing, copy number, gene expression and DNA methylation profiling, demonstrated non-linear clonal expansion of the original tumors and identified oncogenic pathways driving progression. These include activation of the MYC and RTK-RAS-PI3K pathways, up-regulation of the FOXM1- and E2F2-mediated cell cycle transition genes, as well as epigenetic silencing of developmental transcriptional factors bound by Polycomb repressive complex 2 in human embryonic stem cells. Our results not only provide mechanistic insight into the genetic and epigenetic mechanisms driving glioma progression but also identify inhibition of the bromodomain and extra-terminal (BET) family as a potential therapeutic approach.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-03T21:53:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001589","title":"Genome_Diversity_in_Africa_Project___GemCode_libraries","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from Africa have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within Africa would facilitate genomic epidemiological studies in the region.The Genome Diversity in Africa Project (GDAP) will extend and expand the African Genome Variation (AGV) project, an international collaboration aimed to produce a comprehensive catalogue of human genetic variation in Sub-Saharan Africa (SSA). Using a sequencing-based approach, GDA project aims to capture human genetic variation in Africa, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in Africa, as well as providing a global resource to help design, implement and interpret genomic studies in African populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out whole genome sequencing at high depth (30x) of up to 1000 individuals across Africa (25 individuals from each ethnolinguistic group). We have already completed sequencing from 5 ethno-linguistic groups and we are now adding others.Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from Africa accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across Africa; 3) develop a cost-efficient, next-generation genotype array for diverse populations across Africa; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics.","abstract":"This is a project on high-coverage, whole-genome sequencing of individuals from Sudan. This set has been sequenced as part of the Genome Diversity in Africa Project (GDAP). The GDAP aims to produce a comprehensive catalogue of human genetic variation in Africa, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in Africa, as well as providing a global resource to help design, implement and interpret genomic studies in African populations and studies comprising globally diverse populations, complementing existing genomic resources.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-05T07:17:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001590","title":"TTV018_RORC_IBD_associated_genotype_effects_on_RORgT_expression_and_function_in_ex_vivo_T_cells","description":"RNA sequencing of peripheral immune cells from patients +/- an IBD risk variant. Peripheral immune cells +/- in vitro test compound treatment.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"ROR?t is a transcriptional regulator of Th17 cell differentiation and is implicated in the pathogenesis of inflammatory diseases. This project aims to determine IBD-associated SNP effects on RORgT/Th17 expression and function using a genotype-driven experimental approach in ex vivo peripheral immune cells.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-05T14:56:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001591","title":"RNAseq_of_ribosomal_footprints","description":"Cancer genes can affect ribosomal RNA processing and this can underlie their essentiality to cells, making them cell-essential in the same way as ribosomal genes themselves. We want to confirm this, in order to understand the results of our CRISPR drop-out screens.NOTE FROM BESPOKE TEAM: Run a single read 1 (forward read) of 30 bases, then an index 1 read as normal.  This would fit a 50cycle kit","abstract":"Cancer genes can affect ribosomal RNA processing and this can underlie their essentiality to cells, making them cell-essential in the same way as ribosomal genes themselves. We want to confirm this, in order to understand the results of our CRISPR drop-out screens","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-05T15:43:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001592","title":"Thu_Nov_05_15_53_00_GMT_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001593","title":"Thu_Nov_05_15_53_43_GMT_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001594","title":"Thu_Nov_05_15_53_46_GMT_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001595","title":"Epigenetic dynamics of monocyte to macrophage differentiation","description":"Monocyte to macrophage differentiation involves major biochemical and structural changes in non-dividing cells. In order to elucidate the role of gene regulatory changes during this process, we used high-throughput sequencing to analyze the complete transcriptome and epigenome of human monocytes that were isolated by elutriation and differentiated in vitro by addition of MCSF in serum-free medium. We also investigated the effect of loading the macrophages with modified LDL. We found that many mRNAs and miRNAs were significantly up- or downregulated during differentiation. While there was no correlation between gene expression and DNA methylation changes at transcription start sites, we identified a large number of intra- and intergenic regions that rapidly lost DNA methylation, became nucleosome-free and gained histone marks indicative of active enhancers. Loading of macrophages with modified LDL caused gene expression changes, but no chromatin changes. In summary, our results demonstrate that monocyte to macrophage differentiation is associated with rapid, highly targeted epigenetic changes, whereas lipid uptake mainly affects regulatory circuits of soluble factors.","abstract":"Monocyte to macrophage differentiation involves major biochemical and structural changes in non-dividing cells. In order to elucidate the role of gene regulatory changes during this process, we used high-throughput sequencing to analyze the complete transcriptome and epigenome of human monocytes that were isolated by elutriation and differentiated in vitro by addition of MCSF in serum-free medium. We also investigated the effect of loading the macrophages with modified LDL. We found that many mRNAs and miRNAs were significantly up- or downregulated during differentiation. While there was no correlation between gene expression and DNA methylation changes at transcription start sites, we identified a large number of intra- and intergenic regions that rapidly lost DNA methylation, became nucleosome-free and gained histone marks indicative of active enhancers. Loading of macrophages with modified LDL caused gene expression changes, but no chromatin changes. In summary, our results demonstrate that monocyte to macrophage differentiation is associated with rapid, highly targeted epigenetic changes, whereas lipid uptake mainly affects regulatory circuits of soluble factors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-06T09:35:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001596","title":"BLUEPRINT ATAC-seq data for cells in the haematopoietic lineages, from adult and cord blood samples","description":"BLLUEPRINT ATAC-seq data for cells in the haematopoietic lineages, from adult and cord blood samples.","abstract":"BLLUEPRINT ATAC-seq data for cells in the haematopoietic lineages, from adult and cord blood samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-09T15:20:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001597","title":"Low_depth_whole_genome_sequencing_across_multiple_isolated_populations","description":"Isolated populations have unique population genetics characteristics that can help boost power in genetic association studies for complex traits. Leveraging these advantageous characteristics requires an in-depth understanding of parameters that have shaped sequence variation in isolates. This study performs a comprehensive investigation of these parameters using low-depth whole genome sequencing (WGS) across multiple isolates.","abstract":"Isolated populations have unique population genetics characteristics that can help boost power in genetic association studies for complex traits. Leveraging these advantageous characteristics requires an in-depth understanding of parameters that have shaped sequence variation in isolates. This study performs a comprehensive investigation of these parameters using low-depth whole genome sequencing (WGS) across multiple isolates.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-10T09:50:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001598","title":"BLUEPRINT DNA methylation profiles of monocytes, T cells and B cells in type 1 diabetes-discordant monozygotic twins","description":"BLUEPRINT DNA methylation profiles of monocytes, T cells and B cells in type 1 diabetes-discordant monozygotic twins","abstract":"BLUEPRINT DNA methylation profiles of monocytes, T cells and B cells in type 1 diabetes-discordant monozygotic twins","study_type":"Other","pubmed_ids":[27898055],"external_links":null,"is_released":true,"released_date":"2015-11-10T18:36:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001599","title":"A genetic compendium  of human brains from the UK Medical Research Council brain tissue resource","description":"Common neurodegenerative diseases have a complex genetic architecture. Highly penetrant diseases alleles are found in a significant minority of cases, and common risk alleles are present in a large proportion. Given the central role of genetic factors in the pathogenesis of these disorders, it is critical that mechanistic studies in human subjects and tissue samples are interpreted in an genetically enlightened context. To address this we performed exome sequencing on 1461 human brains accessible through the Medical Research Council (UK) brain banks network.  Our findings confirm the complex genetic landscape of neurodegenerative disease. Clinical, pathological and genetic data for the 1461 brains with corresponding exome sequencing data are available within this dataset, enabling the genetic stratification and selection of post-mortem tissue samples for researchers.","abstract":"Common neurodegenerative diseases have a complex genetic architecture. Highly penetrant diseases alleles are found in a significant minority of cases, and common risk alleles are present in a large proportion. Given the central role of genetic factors in the pathogenesis of these disorders, it is critical that mechanistic studies in human subjects and tissue samples are interpreted in an genetically enlightened context. To address this we performed exome sequencing on 1461 human brains accessible through the Medical Research Council (UK) brain banks network.  Our findings confirm the complex genetic landscape of neurodegenerative disease. Clinical, pathological and genetic data for the 1461 brains with corresponding exome sequencing data are available within this dataset, enabling the genetic stratification and selection of post-mortem tissue samples for researchers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-11T14:04:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001600","title":"Container Study for ICGC Malignant Lymphoma Master Study (MMML)","description":"Master Container Study for Malignant Lymphoma data (ICGC - Germany)","abstract":"Master Container Study for Malignant Lymphoma data (ICGC - Germany)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-10-11T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001601","title":"Malignant pheochromocytomas/paragangliomas harbor mutations in transport and cell adhesion genes","description":"One out of ten patients with pheochromocytoma (PCC) and paraganglioma (PGL) develop malignant disease. Today there are no reliable pathological methods to predict malignancy at the time of diagnosis. Tumors harboring mutations in the succinate dehydrogenase subunit B (SDHB) gene often metastasize but the sequential genetic events resulting in malignant progression are not fully understood. The aim of this study was to identify somatic mutations that contribute to the malignant transformation of PCC/PGL. We performed pair-wise (tumor-normal) whole-exome sequencing to analyze the somatic mutational landscape in five malignant and four benign primary PCC/sympathetic PGL (sPGL), including two biological replicates from each specimen. In total, 225 unique somatic mutations were identified in 215 genes, with an average mutation rate of 0.54 mutations/megabase. Malignant tumors had a significantly higher number of mutations compared to benign tumors (p&lt;0.001). Three novel genes were identified as recurrently mutated; MYCN, MYO5B and VCL, and mutations in these genes were exclusively found in malignant sPGL tumors. Mutations in the MYO5B gene could be verified in two publicly available data sets. A gene ontology analysis of mutated genes showed enrichment of cellular functions related to cytoskeletal protein binding, myosin complex, and motor activity, many of which had functions in Rab and Rac/Rho GTPase pathways. Conclusively, we have identified recurrent mutations in genes related to intracellular transport and cell adhesion, and we have confirmed recurrent mutations of MYO5B in PCC/PGL cases with malignant potential. Our study suggests that deregulated Rab and Rac/Rho pathways may be important in PCC/PGL tumorigenesis.","abstract":"One out of ten patients with pheochromocytoma (PCC) and paraganglioma (PGL) develop malignant disease. Today there are no reliable pathological methods to predict malignancy at the time of diagnosis. Tumors harboring mutations in the succinate dehydrogenase subunit B (SDHB) gene often metastasize but the sequential genetic events resulting in malignant progression are not fully understood. The aim of this study was to identify somatic mutations that contribute to the malignant transformation of PCC/PGL. We performed pair-wise (tumor-normal) whole-exome sequencing to analyze the somatic mutational landscape in five malignant and four benign primary PCC/sympathetic PGL (sPGL), including two biological replicates from each specimen. In total, 225 unique somatic mutations were identified in 215 genes, with an average mutation rate of 0.54 mutations/megabase. Malignant tumors had a significantly higher number of mutations compared to benign tumors (p&lt;0.001). Three novel genes were identified as recurrently mutated; MYCN, MYO5B and VCL, and mutations in these genes were exclusively found in malignant sPGL tumors. Mutations in the MYO5B gene could be verified in two publicly available data sets. A gene ontology analysis of mutated genes showed enrichment of cellular functions related to cytoskeletal protein binding, myosin complex, and motor activity, many of which had functions in Rab and Rac/Rho GTPase pathways. Conclusively, we have identified recurrent mutations in genes related to intracellular transport and cell adhesion, and we have confirmed recurrent mutations of MYO5B in PCC/PGL cases with malignant potential. Our study suggests that deregulated Rab and Rac/Rho pathways may be important in PCC/PGL tumorigenesis.","study_type":"Other","pubmed_ids":[26650627],"external_links":null,"is_released":true,"released_date":"2015-11-18T07:58:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001602","title":"Germline Mutations in Cancer Predisposition Genes in 1,120 Children with Cancer","description":"The identification of predisposing germline mutations in children with cancer enhances understanding of tumorigenesis, directs patient care and enables genetic counseling of patients and families. Nonetheless, the prevalence and spectrum of predisposing mutations are largely unknown.Germline mutations in cancer predisposing genes were identified in 8.5% of the pediatric cancer patients studied. Family history alone failed to predict the presence of an underlying predisposition syndrome in most patients.","abstract":"The identification of predisposing germline mutations in children with cancer enhances understanding of tumorigenesis, directs patient care and enables genetic counseling of patients and families. Nonetheless, the prevalence and spectrum of predisposing mutations are largely unknown.Germline mutations in cancer predisposing genes were identified in 8.5% of the pediatric cancer patients studied. Family history alone failed to predict the presence of an underlying predisposition syndrome in most patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001603","title":"The spatial organization of intratumor heterogeneity andevolutionary trajectories of metastases in hepatocellular carcinoma","description":"Hepatocellular carcinoma (HCC) has one of the poorest survival amongst cancers. Using multi-regional sampling of nine resected HCC with different etiologies, we find that phylogenetic relationships of these sectors show diverse levels of genetic sharing spanning early to late diversification. Unlike the variegated pattern found in colorectal cancers, a large proportion of HCC display a clear Isolation-By-Distance pattern where spatially closer sectors are genetically more similar. Two resected intra-hepatic metastases showed genetic divergence occurring before and after primary tumor diversification respectively. Interestingly, metastatic tumors had much higher variability than their primary tumors, suggesting that intra-hepatic metastasis is accompanied by rapid diversification at the distant location. The presence of co-existing mutations offers the possibility of drug repositioning for HCC treatment. Taken together, these insights into intra-tumor heterogeneity allow for a comprehensive understanding of the evolutionary trajectories of HCC and suggest novel avenues for personalized therapy.","abstract":"Hepatocellular carcinoma (HCC) has one of the poorest survival amongst cancers. Using multi-regional sampling of nine resected HCC with different etiologies, we find that phylogenetic relationships of these sectors show diverse levels of genetic sharing spanning early to late diversification. Unlike the variegated pattern found in colorectal cancers, a large proportion of HCC display a clear Isolation-By-Distance pattern where spatially closer sectors are genetically more similar. Two resected intra-hepatic metastases showed genetic divergence occurring before and after primary tumor diversification respectively. Interestingly, metastatic tumors had much higher variability than their primary tumors, suggesting that intra-hepatic metastasis is accompanied by rapid diversification at the distant location. The presence of co-existing mutations offers the possibility of drug repositioning for HCC treatment. Taken together, these insights into intra-tumor heterogeneity allow for a comprehensive understanding of the evolutionary trajectories of HCC and suggest novel avenues for personalized therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-19T05:32:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001604","title":"Identifying_new_diagnostic_and_treatment_pathways_for_patients_with_unclassifiable_sarcomas","description":"Whole genome sequencing of tumour normal pairs of human undifferentiated sarcomas.","abstract":"Sarcomas are heterogenous mesenchymal cancers that are classified into about 100 pathological subtypes based on their line of differentiation.Up to a quarter of sarcomas are not readily classifiable using routine diagnostic methods and are designated as sarcoma Not Otherwise Specified/undifferentiated/unclassified sarcomas (referred to as UCS henceforth).The diagnosis of UCS is based on fallible criteria and subject to inconsistencies of nomenclature, resulting in the grouping together of biologically unrelated tumours. Consequently the clinical outcomes for this group are not directly comparable between centres and have, in general, stagnated for decades.I aim to address these inconsistencies by using a biobank resource of sarcomas from the Royal National Orthopaedic Hospital (RNOH) collected for over a decade and for which comprehensive clinical, pathological and outcome data are available. This will be complemented by archived paraffin embedded tumour material from the RNOH. The investigation will be performed using both targeted gene sequencing and whole genome sequencing to catalogue the spectrum and nature of somatic genomic rearrangements, point mutations, insertions and deletions that are present in both UCS with the aims of defining a new genetic classification. This will be the first and largest comprehensive investigation of these tumours performed at high resolution.The analysis will be performed by myself with the assistance of the Cancer Genome Project under the guidance of Prof Peter Campbell at the Wellcome Trust Sanger Institute.My key research questions that relate to difficult to classify sarcomas are:How can we exploit the current advances in sequencing technology to:a)Develop an objective, reproducible means to classify currently “unclassifiable” sarcomas? b)Stratify unclassifiable sarcoma patients for more personalised therapy based on the genetics of their tumours?c)Provide a genetic framework for the development of pre-clinical models to better understand the processes of sarcomagenesis in UCS?","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-19T11:51:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001605","title":"Targeted sequencing of 12 genes in patients with HLH","description":"Hemophagocytic lymphohistiocytosis (HLH) is a rapid-onset, potentially fatal hyperinflammatory syndrome. A prompt molecular diagnosis is crucial for appropriate clinical management. Here, we validated and prospectively evaluated a targeted high-throughput sequencing approach for HLH diagnostics. We have carried out high-throughput sequencing of 12 genes linked to HLH  in 58 HLH patients. We achieved a diagnosis in 22 out of 58 patients (38%). Genetically undiagnosed HLH patients had a later age at onset and manifested higher frequencies of known secondary HLH triggers. Rare, putatively pathogenic monoallelic variants were identified in 9 patients. Almost all cases with reduced natural killer (NK) cell function received a diagnosis, but the majority of the prospective cases remain genetically unexplained, highlighting genetic heterogeneity and environmental impact within HLH. A complete understanding of the genetic susceptibility to HLH thus requires further in-depth investigations, including genome sequencing and detailed immunological characterization.","abstract":"Hemophagocytic lymphohistiocytosis (HLH) is a rapid-onset, potentially fatal hyperinflammatory syndrome. A prompt molecular diagnosis is crucial for appropriate clinical management. Here, we validated and prospectively evaluated a targeted high-throughput sequencing approach for HLH diagnostics. We have carried out high-throughput sequencing of 12 genes linked to HLH  in 58 HLH patients. We achieved a diagnosis in 22 out of 58 patients (38%). Genetically undiagnosed HLH patients had a later age at onset and manifested higher frequencies of known secondary HLH triggers. Rare, putatively pathogenic monoallelic variants were identified in 9 patients. Almost all cases with reduced natural killer (NK) cell function received a diagnosis, but the majority of the prospective cases remain genetically unexplained, highlighting genetic heterogeneity and environmental impact within HLH. A complete understanding of the genetic susceptibility to HLH thus requires further in-depth investigations, including genome sequencing and detailed immunological characterization.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-19T13:56:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001606","title":"Homozygous loss-of-function variants in European cosmopolitan and isolate populations","description":"Homozygous loss of function (HLOF) variants provide a valuable window on gene function in humans, as well as an inventory of the human genes that are not essential for survival and reproduction. All humans carry at least a few HLOF variants, but the exact number of inactivated genes that can be tolerated is currently unknown-as are the phenotypic effects of losing function for most human genes. Here, we make use of 1432 whole exome sequences from five European populations to expand the catalogue of known human HLOF mutations; after stringent filtering of variants in our dataset, we identify a total of 173 HLOF mutations, 76 (44%) of which have not been observed previously. We find that population isolates are particularly well suited to surveys of novel HLOF genes because individuals in such populations carry extensive runs of homozygosity, which we show are enriched for novel, rare HLOF variants. Further, we make use of extensive phenotypic data to show that most HLOFs, ascertained in population-based samples, appear to have little detectable effect on the phenotype. On the contrary, we document several genes directly implicated in disease that seem to tolerate HLOF variants. Overall HLOF genes are enriched for olfactory receptor function and are expressed in testes more often than expected, consistent with reduced purifying selection and incipient pseudogenisation.","abstract":"Homozygous loss of function (HLOF) variants provide a valuable window on gene function in humans, as well as an inventory of the human genes that are not essential for survival and reproduction. All humans carry at least a few HLOF variants, but the exact number of inactivated genes that can be tolerated is currently unknown-as are the phenotypic effects of losing function for most human genes. Here, we make use of 1432 whole exome sequences from five European populations to expand the catalogue of known human HLOF mutations; after stringent filtering of variants in our dataset, we identify a total of 173 HLOF mutations, 76 (44%) of which have not been observed previously. We find that population isolates are particularly well suited to surveys of novel HLOF genes because individuals in such populations carry extensive runs of homozygosity, which we show are enriched for novel, rare HLOF variants. Further, we make use of extensive phenotypic data to show that most HLOFs, ascertained in population-based samples, appear to have little detectable effect on the phenotype. On the contrary, we document several genes directly implicated in disease that seem to tolerate HLOF variants. Overall HLOF genes are enriched for olfactory receptor function and are expressed in testes more often than expected, consistent with reduced purifying selection and incipient pseudogenisation.","study_type":"Other","pubmed_ids":[26173456],"external_links":null,"is_released":true,"released_date":"2015-11-19T15:19:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001607","title":"Targeted sequencing of brain expressed miRNA genes","description":"As regulators of gene expression, microRNAs (miRNAs) are likely to play an important role in the development of disease. In this study we present a large-scale strategy to identify miRNAs with a role in the regulation of neuronal processes by screening 289 brain expressed miRNAs. Thereby we found variant rs7861254 located near the MIR204 gene to be significantly associated with schizophrenia. This variant resulted in reduced expression of miR-204 in neuronal-like SH-SY5Y cells.","abstract":"As regulators of gene expression, microRNAs (miRNAs) are likely to play an important role in the development of disease. In this study we present a large-scale strategy to identify miRNAs with a role in the regulation of neuronal processes by screening 289 brain expressed miRNAs. Thereby we found variant rs7861254 located near the MIR204 gene to be significantly associated with schizophrenia. This variant resulted in reduced expression of miR-204 in neuronal-like SH-SY5Y cells.","study_type":"Other","pubmed_ids":[26714269],"external_links":null,"is_released":true,"released_date":"2015-11-21T16:00:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001608","title":"All available datasets of DEEP","description":"All available datasets of DEEP. There are several Reference Epigenomes available. For metadata check out www.deep.dkfz.de One reference epigenome represents a set of 6 ChIP-Seqs, WGBS, RNA-Seq, smallRNA-Seq and sometimes DNase1 and/or NOME-Seq.","abstract":"All available datasets of DEEP. There are several Reference Epigenomes available. For metadata check out www.deep.dkfz.de One reference epigenome represents a set of 6 ChIP-Seqs, WGBS, RNA-Seq, smallRNA-Seq and sometimes DNase1 and/or NOME-Seq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-24T09:01:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001609","title":"DDD_Exomes","description":"We propose to apply state of the art molecular testing, including SNP genotyping, to 12,000 UK children with abnormal development. The results will provide a unique, on-line catalogue of genetic changes linked to symptoms that will enable clinicians to diagnose developmental disorders. Furthermore, we will design more efficient and cheaper diagnostic assays for relevant genetic testing to be offered to all such patients in the UK and so transform clinical practice for children with abnormal development.","abstract":"Thousands of babies are born each year in the UK who fail to develop normally because of errors in their genetic makeup. Currently, diagnosis is restricted to a small minority of children and requires the clinician to recognise the appearance of the child and the pattern of symptoms, supplemented by the use of microscopes to identify large rearrangements of the genetic material in chromosomes. Research shows that the latest molecular testing methods identify previously undetectable changes in chromosomes allowing new diagnoses to be made. However, clinical use is hampered by the limited availability and inconsistent application of these technologies, and by lack of basic knowledge to link genetic changes directly to symptoms. The consequence is that clinical diagnoses remain impossible except for a small number of children.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001610","title":"We screened 2.5 million SNPs in 161 individuals from 13 Sahelian populations from Western, Central and Eastern parts of the belt, and including both nomadic and sedentary groups","description":"We confirmed the role of the Sahel belt as a main corridor for human migrations across the African continent. Strong admixture was observed in both Central and Eastern Sahelian populations, with North Africans and Near Eastern/Arabians respectively, but it was inexistent in Western Sahelian populations. Genome-wide local ancestry inference in admixed Sahelian populations revealed several candidate regions that were significantly enriched for non-autochthonous haplotypes, and many showed to be under positive selection.","abstract":"We confirmed the role of the Sahel belt as a main corridor for human migrations across the African continent. Strong admixture was observed in both Central and Eastern Sahelian populations, with North Africans and Near Eastern/Arabians respectively, but it was inexistent in Western Sahelian populations. Genome-wide local ancestry inference in admixed Sahelian populations revealed several candidate regions that were significantly enriched for non-autochthonous haplotypes, and many showed to be under positive selection.","study_type":"Other","pubmed_ids":[26614524],"external_links":null,"is_released":true,"released_date":"2015-11-24T17:22:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001611","title":"FetalQuant-SD: Accurate quantification of fetal DNA fraction by shallow-depth sequencing of maternal plasma DNA","description":"Noninvasive prenatal testing using massively parallel sequencing of maternal plasma DNA has been rapidly adopted in clinical use worldwide. Fetal DNA fraction in a maternal plasma sample is an important parameter for accurate interpretations of these tests. However, there is a lack of methods involving low-sequencing depth and yet would allow a robust and accurate determination of fetal DNA fraction in maternal plasma for all pregnancies. In this study, we have developed a new method to accurately quantify the fetal DNA fraction by analysing the maternal genotypes and sequencing data of maternal plasma DNA. Fetal DNA fraction was calculated based on the proportion of non-maternal alleles at single-nucleotide polymorphisms where the mother is homozygous. This new approach achieves a median deviation of 0.6% between predicted fetal DNA fraction and the actual fetal DNA fraction using as low as 0.03-fold sequencing coverage of the human genome. We believe that this method will further enhance the clinical interpretations of noninvasive prenatal testing using genome-wide random sequencing.","abstract":"Noninvasive prenatal testing using massively parallel sequencing of maternal plasma DNA has been rapidly adopted in clinical use worldwide. Fetal DNA fraction in a maternal plasma sample is an important parameter for accurate interpretations of these tests. However, there is a lack of methods involving low-sequencing depth and yet would allow a robust and accurate determination of fetal DNA fraction in maternal plasma for all pregnancies. In this study, we have developed a new method to accurately quantify the fetal DNA fraction by analysing the maternal genotypes and sequencing data of maternal plasma DNA. Fetal DNA fraction was calculated based on the proportion of non-maternal alleles at single-nucleotide polymorphisms where the mother is homozygous. This new approach achieves a median deviation of 0.6% between predicted fetal DNA fraction and the actual fetal DNA fraction using as low as 0.03-fold sequencing coverage of the human genome. We believe that this method will further enhance the clinical interpretations of noninvasive prenatal testing using genome-wide random sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-26T02:12:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001612","title":"Exome sequencing of uterine leiomyosarcomas","description":"Uterine leiomyosarcomas (ULMSs) are aggressive smooth muscle tumors associated with poor clinical outcome. Despite previous cytogenetic and molecular studies, their molecular background has remained elusive. To examine somatic variation in ULMS, we performed exome sequencing on 19 tumors. Altogether 43 genes were mutated in at least two ULMSs. Most frequently mutated genes included tumor protein P53 (TP53; 6/19; 33%), alpha thalassemia/mental retardation syndrome X-linked (ATRX; 5/19; 26%), and mediator complex subunit 12 (MED12; 4/19; 21%). Unlike ATRX mutations, both TP53 and MED12 alterations have repeatedly been associated with ULMSs. All the observed ATRX alterations were either nonsense or frameshift mutations. ATRX protein levels were reliably analyzed by immunohistochemistry in altogether 44 ULMSs, and the majority of tumors (23/44; 52%) showed clearly reduced expression. Loss of ATRX expression has been associated with alternative lengthening of telomeres (ALT), and thus the telomere length was analyzed with telomere-specific fluorescence in situ hybridization. The ALT phenotype was confirmed in all ULMSs showing diminished ATRX expression. Exome data also revealed one nonsense mutation in death-domain associated protein (DAXX), another gene previously associated with ALT, and the tumor showed ALT positivity. Aberrant expression of both TP53 and ATRX were associated with poor overall survival. In conclusion, exome sequencing revealed that TP53, ATRX, and MED12 are frequently mutated in ULMSs. ALT phenotype was commonly seen in tumors, indicating that ATR inhibitors, which were recently suggested as possible new drugs for ATRX-deficient tumors, could provide a potential novel therapeutic option for ULMS.","abstract":"Uterine leiomyosarcomas (ULMSs) are aggressive smooth muscle tumors associated with poor clinical outcome. Despite previous cytogenetic and molecular studies, their molecular background has remained elusive. To examine somatic variation in ULMS, we performed exome sequencing on 19 tumors. Altogether 43 genes were mutated in at least two ULMSs. Most frequently mutated genes included tumor protein P53 (TP53; 6/19; 33%), alpha thalassemia/mental retardation syndrome X-linked (ATRX; 5/19; 26%), and mediator complex subunit 12 (MED12; 4/19; 21%). Unlike ATRX mutations, both TP53 and MED12 alterations have repeatedly been associated with ULMSs. All the observed ATRX alterations were either nonsense or frameshift mutations. ATRX protein levels were reliably analyzed by immunohistochemistry in altogether 44 ULMSs, and the majority of tumors (23/44; 52%) showed clearly reduced expression. Loss of ATRX expression has been associated with alternative lengthening of telomeres (ALT), and thus the telomere length was analyzed with telomere-specific fluorescence in situ hybridization. The ALT phenotype was confirmed in all ULMSs showing diminished ATRX expression. Exome data also revealed one nonsense mutation in death-domain associated protein (DAXX), another gene previously associated with ALT, and the tumor showed ALT positivity. Aberrant expression of both TP53 and ATRX were associated with poor overall survival. In conclusion, exome sequencing revealed that TP53, ATRX, and MED12 are frequently mutated in ULMSs. ALT phenotype was commonly seen in tumors, indicating that ATR inhibitors, which were recently suggested as possible new drugs for ATRX-deficient tumors, could provide a potential novel therapeutic option for ULMS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-26T08:17:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001613","title":"GILD_ExomeSeq_PTNHL","description":"This study is meant to gain further knowledge in haematological cancers. Patients samples (mainly DNAs or PCR products) from haematolocical cancer patients will be sequenced, and the outputs will be correlated to their diagnosis and/or prognosis; the findings may also add more insight into the understanding of biology in this type of tumour. We will be sequencing Primary Testicular Lymphomas (PTL) to identify genetic drivers of this rare cancer","abstract":"Advances in genomics have led to the identification of a number of recurrently mutated genes in haematological malignancies. Many of these influence prognosis and response to therapy. The detailed analysis of haematological cancer samples can greatly facilitate patient management. This study will test on a specific subset of samples to inquiry specific alterations not yet identified.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-26T10:50:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001614","title":"Melanoma_C32_ENU_resistance_to_Combination_Therapy","description":"This study involves mutagenizing C32, a melanoma cell line, with ENU to identify those mutations which engender resistance to a targeted treatment.","abstract":"In the last decade we have begun to move towards the use of targeted therapeutics in the clinic, often resulting in dramatic response rates in cancer patients. However, clinical experience has demonstrated time and time again that such responses are invariably followed by the development of drug resistance. Identification of the underlying mechanisms may enable us to reverse such resistance. Traditional methods of modelling this resistance in vitro can lead to a plethora of potential resistance mechanisms that can be difficult to decipher.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-11-26T11:14:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001615","title":"MED12L Gene Alterations Define Aggressive BRCA2-Mutant Prostate Cancers","description":"Germline mutation of BRCA2 increases the lifetime risk of developing prostate cancer (PCa) by over 700%. BRCA2-mutant PCa have poorer prognosis than sporadic PCa, with rapid development of metastatic, castrate-resistant prostate cancer (mCRPC) and 5-year cancer-specific survival rates of ~50-60%1-4. Despite this, unique genomic driver events that explain the aggressiveness of localized BRCA2-mutant PCa are lacking. We used whole-genome sequencing to fully characterize 14 BRCA2-mutant PCa and demonstrate that BRCA2-mutant PCa is associated with increased genetic instability and a mutually exclusive mutational burden when compared to sporadic PCa. Importantly, BRCA2-mutated cancers are defined by unique copy number gains and hypomethylation events, including alterations in the MED12L/MED12 axis, which are found solely in mCRPC and are enriched in PCa tumours harbouring aggressive intraductal carcinoma (IDC-P) pathologic sub-types. Our findings begin to explain the clinical entity of BRCA2-mutated PCa as these tumours have a unique and aggressive genotype de novo, associated with IDC-P and mCRPC, even in the hormone-naive setting.","abstract":"Germline mutation of BRCA2 increases the lifetime risk of developing prostate cancer (PCa) by over 700%. BRCA2-mutant PCa have poorer prognosis than sporadic PCa, with rapid development of metastatic, castrate-resistant prostate cancer (mCRPC) and 5-year cancer-specific survival rates of ~50-60%1-4. Despite this, unique genomic driver events that explain the aggressiveness of localized BRCA2-mutant PCa are lacking. We used whole-genome sequencing to fully characterize 14 BRCA2-mutant PCa and demonstrate that BRCA2-mutant PCa is associated with increased genetic instability and a mutually exclusive mutational burden when compared to sporadic PCa. Importantly, BRCA2-mutated cancers are defined by unique copy number gains and hypomethylation events, including alterations in the MED12L/MED12 axis, which are found solely in mCRPC and are enriched in PCa tumours harbouring aggressive intraductal carcinoma (IDC-P) pathologic sub-types. Our findings begin to explain the clinical entity of BRCA2-mutated PCa as these tumours have a unique and aggressive genotype de novo, associated with IDC-P and mCRPC, even in the hormone-naive setting.","study_type":"Other","pubmed_ids":[28067867],"external_links":null,"is_released":true,"released_date":"2015-11-27T12:18:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001616","title":"Mon_Nov_30_10_17_18_GMT_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001617","title":"Mon_Nov_30_10_18_00_GMT_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001618","title":"Mon_Nov_30_10_18_04_GMT_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001619","title":"Mon_Nov_30_12_55_45_GMT_2015_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001620","title":"Mon_Nov_30_12_56_32_GMT_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001621","title":"Mon_Nov_30_12_56_36_GMT_2015_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001622","title":"High prevalence of TP53 mutations is associated with poor survival and epithelial-mesenchymal transition signature in gliosarcoma patients","description":"Gliosarcoma (GS) is a rare variant (2%) of glioblastoma (GBM) and poses clinical genomic challenges because of poor prognosis and limited genomic information. To understand the molecular etiology of GS, we applied whole-exome sequencing for 28 GS cases from different patient cohorts. Mutations of TP53 were more predominantly prevalent in GS cases (70% (20/28)) compared to GBM cases (32% (29/90)), and GS patients with TP53 mutations showed a significantly shorter survival (P = 0.019).","abstract":"Gliosarcoma (GS) is a rare variant (2%) of glioblastoma (GBM) and poses clinical genomic challenges because of poor prognosis and limited genomic information. To understand the molecular etiology of GS, we applied whole-exome sequencing for 28 GS cases from different patient cohorts. Mutations of TP53 were more predominantly prevalent in GS cases (70% (20/28)) compared to GBM cases (32% (29/90)), and GS patients with TP53 mutations showed a significantly shorter survival (P = 0.019).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001623","title":"Pediatric Whole Genome Sequencing Diagnostic Utility","description":"The standard of care for first-tier clinical investigation of the etiology of congenital malformations and neurodevelopmental disorders is chromosome microarray analysis (CMA) for copy number variations (CNVs), often followed by gene(s)-specific sequencing searching for smaller insertion-deletions (indels) and single nucleotide variant (SNV) mutations. We compared diagnostic rate of WGS to CMA and targeted gene testing of 100 patients referred to The Hospital for Sick Children Genetics clinic in 2014. WGS identified genetic variants meeting clinical diagnostic criteria in 34% of cases, representing a 4-fold increase in diagnostic rate over CMA (8%) (p-value = 1.42e-05) alone and &gt;2-fold increase in CMA plus targeted gene sequencing (13%) (p-value = 0.0009). WGS identified all rare clinically significant CNVs that were detected by CMA. In an additional 26 patients, WGS revealed indel and missense mutations presenting in a dominant (63%) or a recessive (37%) manner. We found four subjects with mutations in at least two genes associated with distinct genetic disorders, including two cases harboring a pathogenic CNV and SNV. When considering medically actionable secondary findings in addition to primary WGS findings, 38% of patients would benefit from genetic counselling.","abstract":"The standard of care for first-tier clinical investigation of the etiology of congenital malformations and neurodevelopmental disorders is chromosome microarray analysis (CMA) for copy number variations (CNVs), often followed by gene(s)-specific sequencing searching for smaller insertion-deletions (indels) and single nucleotide variant (SNV) mutations. We compared diagnostic rate of WGS to CMA and targeted gene testing of 100 patients referred to The Hospital for Sick Children Genetics clinic in 2014. WGS identified genetic variants meeting clinical diagnostic criteria in 34% of cases, representing a 4-fold increase in diagnostic rate over CMA (8%) (p-value = 1.42e-05) alone and &gt;2-fold increase in CMA plus targeted gene sequencing (13%) (p-value = 0.0009). WGS identified all rare clinically significant CNVs that were detected by CMA. In an additional 26 patients, WGS revealed indel and missense mutations presenting in a dominant (63%) or a recessive (37%) manner. We found four subjects with mutations in at least two genes associated with distinct genetic disorders, including two cases harboring a pathogenic CNV and SNV. When considering medically actionable secondary findings in addition to primary WGS findings, 38% of patients would benefit from genetic counselling.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-12-01T15:58:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001624","title":"Epigenetic profiling of human CD4+ memory T cells reveals their proliferative history and argues in favor of a progressive differentiation model driven by epigenetically controlled master regulators.","description":"A key element of adaptive immunity is the development of long-lived memory cells, which protect against recurring infection by providing a highly enriched pool of antigen-specific cells ready to react to the pathogen. Different classes of memory T cells occur upon primary activation of naive T cells, however, their detailed differentiation pathway is not entirely clear. As part of the IHEC consortium, we generated genome-wide epigenetic maps of a number of CD4+ T cell memory (Tmem) stages including rare subsets such as terminally differentiated (TEMRA) and bone marrow-resident Tmem. We found that CD4+ T cells show progressive global DNA demethylation with differentiation into memory stages, which reflects their proliferative history and likely indicates their decline in differentiation and proliferation potential. Furthermore, transcriptomic profiling combined with co-regulation network analyses arranged different Tmem subsets into a successive differentiation pathway. In addition, we identified a number of epigenetically controlled candidate master regulators for Tmem formation, of which we functionally validated a new methylation-sensitive promoter for the known 'naive-keeper' transcription factor Foxp1. Our study highlights the power of epigenomic datasets in the elucidation of the cellular history but also of the functional potential of T cell populations including the identification of epigenetically controlled master regulators.","abstract":"A key element of adaptive immunity is the development of long-lived memory cells, which protect against recurring infection by providing a highly enriched pool of antigen-specific cells ready to react to the pathogen. Different classes of memory T cells occur upon primary activation of naive T cells, however, their detailed differentiation pathway is not entirely clear. As part of the IHEC consortium, we generated genome-wide epigenetic maps of a number of CD4+ T cell memory (Tmem) stages including rare subsets such as terminally differentiated (TEMRA) and bone marrow-resident Tmem. We found that CD4+ T cells show progressive global DNA demethylation with differentiation into memory stages, which reflects their proliferative history and likely indicates their decline in differentiation and proliferation potential. Furthermore, transcriptomic profiling combined with co-regulation network analyses arranged different Tmem subsets into a successive differentiation pathway. In addition, we identified a number of epigenetically controlled candidate master regulators for Tmem formation, of which we functionally validated a new methylation-sensitive promoter for the known 'naive-keeper' transcription factor Foxp1. Our study highlights the power of epigenomic datasets in the elucidation of the cellular history but also of the functional potential of T cell populations including the identification of epigenetically controlled master regulators.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-12-01T16:28:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001625","title":"PSCP_bisulphite_analysis_in_hESCs","description":"Many studies over the past 10 years, culminating in the recent report of the International Stem Cell Initiative (ISCI, 2011) have shown that hPSC acquire genetic and epigenetic changes during their time in culture. Many of the genetic changes are non-random and recurrent, probably because they provide a selective growth advantage to the undifferentiated cells. Some are shared by embryonal carcinoma cells, the malignant counterparts of ES cells. The origins of these growth advantages are poorly understood, but may come from altered cell cycle dynamics, resistance to apoptosis or altered patterns of differentiation. Less is known about the nature and consequences of epigenetic changes, but it is likely that these similarly affect hPSC behaviour; e.g., enhanced expression of DLK1, an imprinted gene, is associated with altered hPSC growth (Enver et al 2005). Inevitably, these genetic and epigenetic changes will impact on our ability to use hPSC for regenerative medicine, either because malignant transformation of the undifferentiated cells or their differentiated derivatives to be used for transplantation compromises safety, or because they impede the function of those differentiated derivatives, or because they affect the efficiency with which the undifferentiated cells can be expanded and differentiated into desired cell types. Focusing initially upon the existing clinical grade hESC lines, later moving to iPSC, we will Consolidate and extend knowledge of the rate, type and functional impact of the genetic variations that occur during hPSC culture. We will use whole genome and exome sequencing as well as SNP arrays, together with clonal analysis and other cytogenetics techniques. Common changes will be compared with those found in the normal human population, at low frequency in the original cell population or observed during iPSC generation in the HIPSCI project currently based at the WTSI. These studies will provide a better understanding of the range of genetic changes that occur in hPSC beyond the CNVs already identified. In conjunction with cancer genome resources and expertise at WTSI, bioinformatic analyses of these hPSC data will allow us to assess potential impact on hPSC behaviour pertinent to applications in regenerative medicine, notably the likelihood that specific changes arising in undifferentiated PSC cultures may be associated with potential malignant transformation of differentiated progeny. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The goal of this study is to analyse a total of 80 subcloned hESC lines, which are derived from 2 MasterShef ESC lines by bisulphite sequencing. After this initial study, additional pluripotent stem cell lines may be analysed.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-12-03T10:53:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001626","title":"2015_12_07_10_37_19_149_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001627","title":"2015_12_07_10_37_31_009_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001628","title":"2015_12_07_10_37_31_475_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001629","title":"2015_12_07_10_40_36_768_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001630","title":"2015_12_07_10_40_45_607_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001631","title":"2015_12_07_10_40_46_168_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001632","title":"New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs","description":"Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated “CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)”, “CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)”, “CNS high grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)”, and “CNS high grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)”, will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.","abstract":"Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated “CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)”, “CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)”, “CNS high grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)”, and “CNS high grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)”, will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-12-08T15:15:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001633","title":"Exome sequencing and CRISPR/Cas genome editing identify mutations of ZAK as a cause of limb defects in humans and mice","description":"The CRISPR/Cas technology enables targeted genome editing and the rapid generation of transgenic animal models for the study of human genetic disorders. Here we describe an autosomal recessive human disease in two unrelated families characterized by a split foot defect, nail abnormalities of the hands and hearing loss, due to mutations disrupting the SAM domain of the protein kinase ZAK. ZAK is a member of the MAPKKK family with no known role in limb development. We show that Zak is expressed in the developing limbs and that a CRISPR/Cas-mediated knockout of the two Zak isoforms is embryonically lethal in mice. In contrast, a deletion of the SAM domain induces a complex hindlimb defect associated with downregulation of Trp63, a known split-hand/split-foot malformation disease gene. Our results identify ZAK as a key player in mammalian limb patterning and demonstrate the rapid utility of CRISPR/Cas genome editing to assign causality to human mutations in the mouse in less then 10 weeks.","abstract":"The CRISPR/Cas technology enables targeted genome editing and the rapid generation of transgenic animal models for the study of human genetic disorders. Here we describe an autosomal recessive human disease in two unrelated families characterized by a split foot defect, nail abnormalities of the hands and hearing loss, due to mutations disrupting the SAM domain of the protein kinase ZAK. ZAK is a member of the MAPKKK family with no known role in limb development. We show that Zak is expressed in the developing limbs and that a CRISPR/Cas-mediated knockout of the two Zak isoforms is embryonically lethal in mice. In contrast, a deletion of the SAM domain induces a complex hindlimb defect associated with downregulation of Trp63, a known split-hand/split-foot malformation disease gene. Our results identify ZAK as a key player in mammalian limb patterning and demonstrate the rapid utility of CRISPR/Cas genome editing to assign causality to human mutations in the mouse in less then 10 weeks.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001634","title":"2015_12_14_12_13_23_436_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001635","title":"2015_12_14_12_13_36_661_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001636","title":"2015_12_14_12_13_37_132_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001637","title":"BLUEPRINT DNA Methylation 450K data of mantle cell lymphoma","description":"We have applied an analytic strategy to decipher the DNA methylome of 86 mantle cell lymphomas (MCL) in light of the methylome of the entire B-cell lineage. In this way, we first identified two MCL subgroups that respectively carry epigenetic imprints of pre- and post-germinal center B cells. Secondly, we observed that pure tumor-specific changes are rare, as most (89-99%) DNA methylation alterations in MCL are within or in close proximity of those regions showing dynamic methylation in normal B cells. Several thousand of these differentially methylated regions in MCL show concurrent changes in enhancer-associated histone modifications, including a region located 650 Kb away from the MCL oncogene SOX11. At the clinical level, epigenetic and genetic changes co-evolve during MCL progression and the magnitude of epigenetic changes is associated with overall survival of the patients.","abstract":"We have applied an analytic strategy to decipher the DNA methylome of 86 mantle cell lymphomas (MCL) in light of the methylome of the entire B-cell lineage. In this way, we first identified two MCL subgroups that respectively carry epigenetic imprints of pre- and post-germinal center B cells. Secondly, we observed that pure tumor-specific changes are rare, as most (89-99%) DNA methylation alterations in MCL are within or in close proximity of those regions showing dynamic methylation in normal B cells. Several thousand of these differentially methylated regions in MCL show concurrent changes in enhancer-associated histone modifications, including a region located 650 Kb away from the MCL oncogene SOX11. At the clinical level, epigenetic and genetic changes co-evolve during MCL progression and the magnitude of epigenetic changes is associated with overall survival of the patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-12-16T13:27:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001638","title":"BLUEPRINT Bisulfite-seq and Whole Genome Sequencing of mantle cell lymphoma","description":"Bisulfite-seq and Whole Genome Sequencing of mantle cell lymphoma","abstract":"Bisulfite-seq and Whole Genome Sequencing of mantle cell lymphoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-12-16T13:28:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001639","title":"Amplicon_based_sequencing_of_drug_resistant_organoids","description":"A BRAF V600E colorectal organoid which is sensitive to MAP kinase inhibition was mutagenised with the chemical mutagen ENU and then drug selected using a combination of Trametinib, Dabrafenib and Cetuximab. Single cell derived organoids were then manually picked and expanded in drug. Resistance was confirmed in a 14 day assay and DNA was collected. These then underwent targeted amplicon-based sequencing to confirm candidate resistance effectors from a screen in 2 2D BRAF V600E colorectal cell lines. Pools of resistant clones were also sequenced.","abstract":"A BRAF V600E colorectal organoid was mutagenised with the chemical mutagen ENU and then drug selected. Single cell derived organoids were then manually picked and expanded in drug. Resistance was confirmed and DNA was collected. These then underwent targeted amplicon-based sequencing. Pools of resistant clones were also sequenced.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-12-16T14:55:18+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001640","title":"Characterisation_of_patients_with_TSHomas","description":"TSHomas are a rare cause of thyroid hormone excess, representing 2% of all pituitary adenomas. These tumours are associated with highly variable clinical phenotype. The pathogenesis of these tumours remains poorly understood. This study aims to study the genetic architecture of patients with TSHomas","abstract":"TSHomas are a rare cause of thyroid hormone excess, representing 2% of all pituitary adenomas. These tumours are associated with highly variable clinical phenotype. The pathogenesis of these tumours remains poorly understood. This study aims to study the genetic architecture of patients with TSHomas","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001641","title":"BLUEPRINT Epigenetic characterization of megakaryocytes and erythroblasts","description":"Megakaryocytes and erythroblasts derive from the same progenitor cell type but carry out very different functions. In order to understand how the different functional phenotypes arise we have characterised the epigenetic landscape of these cells.","abstract":"Megakaryocytes and erythroblasts derive from the same progenitor cell type but carry out very different functions. In order to understand how the different functional phenotypes arise we have characterised the epigenetic landscape of these cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-12-17T09:45:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001645","title":"EXOME-WIDE ASSOCIATION ANALYSIS OF CORONARY ARTERY DISEASE IN THE KINGDOM OF SAUDI ARABIA POPULATION","description":"Coronary Artery Disease (CAD) remains the leading cause of mortality worldwide. Mortality rates associated with CAD have shown an exceptional increase particularly in fast developing economies like the Kingdom of Saudi Arabia (KSA). Over the past twenty years, CAD has become the leading cause of death in KSA and has reached epidemic proportions. This rise is undoubtedly caused by fast urbanization that is associated with a life-style that promotes CAD. However, the question remains whether genetics play a significant role and whether genetic susceptibility is increased in KSA compared to the well-studied Western European populations. Therefore, we performed an Exome-wide association study (EWAS) in 832 patients and 1,076 controls of Saudi Arabian origin to test whether population specific, strong genetic risk factors for CAD exist, or whether the polygenic risk score for known genetic risk factors for CAD, lipids, and Type 2 Diabetes show evidence for an enriched genetic burden. Our results do not show significant associations for a single genetic locus. However, the heritability estimate for CAD for this population was high (h2 = 0.53, S.E. = 0.1, p = 4e-12) and we observed a significant association of the polygenic risk score for CAD that demonstrates that the population of KSA, at least in part, shares the genetic risk associated to CAD in Western populations.","abstract":"Coronary Artery Disease (CAD) remains the leading cause of mortality worldwide. Mortality rates associated with CAD have shown an exceptional increase particularly in fast developing economies like the Kingdom of Saudi Arabia (KSA). Over the past twenty years, CAD has become the leading cause of death in KSA and has reached epidemic proportions. This rise is undoubtedly caused by fast urbanization that is associated with a life-style that promotes CAD. However, the question remains whether genetics play a significant role and whether genetic susceptibility is increased in KSA compared to the well-studied Western European populations. Therefore, we performed an Exome-wide association study (EWAS) in 832 patients and 1,076 controls of Saudi Arabian origin to test whether population specific, strong genetic risk factors for CAD exist, or whether the polygenic risk score for known genetic risk factors for CAD, lipids, and Type 2 Diabetes show evidence for an enriched genetic burden. Our results do not show significant associations for a single genetic locus. However, the heritability estimate for CAD for this population was high (h2 = 0.53, S.E. = 0.1, p = 4e-12) and we observed a significant association of the polygenic risk score for CAD that demonstrates that the population of KSA, at least in part, shares the genetic risk associated to CAD in Western populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-12-17T16:17:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001650","title":"This is just a dummy study submission using REST","description":"Just a dummy test for familiarising myself with REST submissions","abstract":"Just a dummy test for familiarising myself with REST submissions","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001651","title":"PanCancer Analysis of Whole Genomes (OLD)","description":"The Pancancer Analysis of Whole Genomes (PCAWG) study is an international collaboration to identify common patterns of mutation in more than 2,800 cancer whole genomes from the International Cancer Genome Consortium. Building upon previous work which examined cancer coding regions (Cancer Genome Atlas Research Network, The Cancer Genome Atlas Pan-Cancer analysis project, Nat. Genet. 2013 45:1113), this project is exploring the nature and consequences of somatic and germline variations in both coding and non-coding regions, with specific emphasis on cis-regulatory sites, non-coding RNAs, and large-scale structural alterations.","abstract":"The Pancancer Analysis of Whole Genomes (PCAWG) study is an international collaboration to identify common patterns of mutation in more than 2,800 cancer whole genomes from the International Cancer Genome Consortium. Building upon previous work which examined cancer coding regions (Cancer Genome Atlas Research Network, The Cancer Genome Atlas Pan-Cancer analysis project, Nat. Genet. 2013 45:1113), this project is exploring the nature and consequences of somatic and germline variations in both coding and non-coding regions, with specific emphasis on cis-regulatory sites, non-coding RNAs, and large-scale structural alterations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001652","title":"Molecular analysis of circulating tumour cells identifies distinct profiles in chemosensitive and chemofractory patients with small cell lung cancer","description":"Most patients with small cell lung cancer (SCLC), a metastatic, aggressive disease are initially chemosensitive but relapse with acquired chemoresistance.  Some patients (~20%), defined as chemorefractory, relapse within 3 months of initial treatment. Molecular mechanisms differentiating chemosensitive from chemorefractory disease are unknown.  We examined circulating tumour cell (CTC) copy number aberrations (CNA) in pre-treatment blood samples to determine their potential as a minimally invasive biomarker to predict chemosensitive versus chemorefractory disease. Analysis of 80 CTC samples from 10 patients generated a CNA classifier correlating with subsequent response and relapse that was verified in 6 independent SCLC patient-derived CTC explants (1).  Longitudinal analysis of CTC CNA from 5 chemosensitive patients who subsequently relapsed and did not respond to chemotherapy rechallenge, failed to recapitulate baseline changes between chemosensitive and chemorefractory disease suggesting different underlying resistance mechanisms. These data highlight CTC utility to interrogate drug resistance and potentially, stratify patients according to predicted chemosensitivity in clinical trials of novel therapeutics.","abstract":"Most patients with small cell lung cancer (SCLC), a metastatic, aggressive disease are initially chemosensitive but relapse with acquired chemoresistance.  Some patients (~20%), defined as chemorefractory, relapse within 3 months of initial treatment. Molecular mechanisms differentiating chemosensitive from chemorefractory disease are unknown.  We examined circulating tumour cell (CTC) copy number aberrations (CNA) in pre-treatment blood samples to determine their potential as a minimally invasive biomarker to predict chemosensitive versus chemorefractory disease. Analysis of 80 CTC samples from 10 patients generated a CNA classifier correlating with subsequent response and relapse that was verified in 6 independent SCLC patient-derived CTC explants (1).  Longitudinal analysis of CTC CNA from 5 chemosensitive patients who subsequently relapsed and did not respond to chemotherapy rechallenge, failed to recapitulate baseline changes between chemosensitive and chemorefractory disease suggesting different underlying resistance mechanisms. These data highlight CTC utility to interrogate drug resistance and potentially, stratify patients according to predicted chemosensitivity in clinical trials of novel therapeutics.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001653","title":"Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma","description":"Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analyzed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined 4 CCA clusters-fluke-positive CCAs (clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations; conversely, fluke-negative CCAs (clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements. Whole-genome analysis highlighted FGFR2 3' untranslated region deletion as a mechanism of FGFR2 upregulation. Integration of noncoding promoter mutations with protein-DNA binding profiles demonstrates pervasive modulation of H3K27me3-associated sites in CCA. Clusters 1 and 4 exhibit distinct DNA hypermethylation patterns targeting either CpG islands or shores-mutation signature and subclonality analysis suggests that these reflect different mutational pathways. Our results exemplify how genetics, epigenetics, and environmental carcinogens can interplay across different geographies to generate distinct molecular subtypes of cancer.SIGNIFICANCE: Integrated whole-genome and epigenomic analysis of CCA on an international scale identifies new CCA driver genes, noncoding promoter mutations, and structural variants. CCA molecular landscapes differ radically by etiology, underscoring how distinct cancer subtypes in the same organ may arise through different extrinsic and intrinsic carcinogenic processes.","abstract":"Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analyzed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined 4 CCA clusters-fluke-positive CCAs (clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations; conversely, fluke-negative CCAs (clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements. Whole-genome analysis highlighted FGFR2 3' untranslated region deletion as a mechanism of FGFR2 upregulation. Integration of noncoding promoter mutations with protein-DNA binding profiles demonstrates pervasive modulation of H3K27me3-associated sites in CCA. Clusters 1 and 4 exhibit distinct DNA hypermethylation patterns targeting either CpG islands or shores-mutation signature and subclonality analysis suggests that these reflect different mutational pathways. Our results exemplify how genetics, epigenetics, and environmental carcinogens can interplay across different geographies to generate distinct molecular subtypes of cancer.SIGNIFICANCE: Integrated whole-genome and epigenomic analysis of CCA on an international scale identifies new CCA driver genes, noncoding promoter mutations, and structural variants. CCA molecular landscapes differ radically by etiology, underscoring how distinct cancer subtypes in the same organ may arise through different extrinsic and intrinsic carcinogenic processes.","study_type":"Other","pubmed_ids":[28667006],"external_links":null,"is_released":true,"released_date":"2015-12-21T07:28:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001654","title":"Spatial and Temporal Homogeneity of Driver Mutations in Diffuse Intrinsic Pointine Glioma","description":"Diffuse Intrinsic Pontine Gliomas (DIPG) are deadly pediatric brain tumors where needle biopsies help guide diagnosis and targeted therapies. To address spatial heterogeneity, we analyzed 134 specimens from various neuroanatomical structures of whole autopsy brains from nine DIPG patients. Evolutionary reconstruction indicates histone 3 (H3)K27M – including novel H3.2K27M - mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumor and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). Later oncogenic alterations arise in sub-clones and often affect the PI3K pathway. Our findings are consistent with early tumor spread outside the brainstem including the cerebrum. The spatial and temporal homogeneity of driver mutations in DIPG implies they will be captured by limited biopsies and emphasizes the need to develop therapies specifically targeting obligate oncohistone partnerships.","abstract":"Diffuse Intrinsic Pontine Gliomas (DIPG) are deadly pediatric brain tumors where needle biopsies help guide diagnosis and targeted therapies. To address spatial heterogeneity, we analyzed 134 specimens from various neuroanatomical structures of whole autopsy brains from nine DIPG patients. Evolutionary reconstruction indicates histone 3 (H3)K27M – including novel H3.2K27M - mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumor and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). Later oncogenic alterations arise in sub-clones and often affect the PI3K pathway. Our findings are consistent with early tumor spread outside the brainstem including the cerebrum. The spatial and temporal homogeneity of driver mutations in DIPG implies they will be captured by limited biopsies and emphasizes the need to develop therapies specifically targeting obligate oncohistone partnerships.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-12-21T21:14:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001655","title":"RNA_seq_analysis_of_transcriptome_variation_with_human_ESC_subclones","description":"Many studies over the past 10 years, culminating in the recent report of the International Stem Cell Initiative (ISCI, 2011) have shown that hPSC acquire genetic and epigenetic changes during their time in culture. Many of the genetic changes are non-random and recurrent, probably because they provide a selective growth advantage to the undifferentiated cells. Some are shared by embryonal carcinoma cells, the malignant counterparts of ES cells. The origins of these growth advantages are poorly understood, but may come from altered cell cycle dynamics, resistance to apoptosis or altered patterns of differentiation. Less is known about the nature and consequences of epigenetic changes, but it is likely that these similarly affect hPSC behaviour; e.g., enhanced expression of DLK1, an imprinted gene, is associated with altered hPSC growth (Enver et al 2005). Inevitably, these genetic and epigenetic changes will impact on our ability to use hPSC for regenerative medicine, either because malignant transformation of the undifferentiated cells or their differentiated derivatives to be used for transplantation compromises safety, or because they impede the function of those differentiated derivatives, or because they affect the efficiency with which the undifferentiated cells can be expanded and differentiated into desired cell types. Focusing initially upon the existing clinical grade hESC lines, later moving to iPSC, we will Consolidate and extend knowledge of the rate, type and functional impact of the genetic variations that occur during hPSC culture. We will use whole genome and exome sequencing as well as SNP arrays, together with clonal analysis and other cytogenetics techniques. Common changes will be compared with those found in the normal human population, at low frequency in the original cell population or observed during iPSC generation in the HIPSCI project currently based at the WTSI. These studies will provide a better understanding of the range of genetic changes that occur in hPSC beyond the CNVs already identified. In conjunction with cancer genome resources and expertise at WTSI, bioinformatic analyses of these hPSC data will allow us to assess potential impact on hPSC behaviour pertinent to applications in regenerative medicine, notably the likelihood that specific changes arising in undifferentiated PSC cultures may be associated with potential malignant transformation of differentiated progenyThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The goal of this study is to analyse a total of 80 subcloned hESC lines, which are derived from 2 MasterShef ESC lines by whole genome sequencing. After this initial study, additional pluripotent stem cell lines may be analysed.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-12-22T08:43:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001656","title":"A unidirectional histone code in bidirectional promoters across cell types","description":"Recent studies indicate that thousands of genes are expressed from bidirectional promoters (BDPs). Gene regulation at BDPs is poorly understood, in particular how the cell is able to regulate them differently. Here we investigate the effect of histone Modifications in BDP regulation. In this study, we model the gene activity using different gene  expression assays, such as RNA-Seq, GRO-cap, and CAGE around the BDP transcription start sites (TSSs) using different histone modifications in various cell types. We develop a new statistical approach that links histone modifications to gene expression at BDPs. It improves over previous methods, because it is able to capture spatial dependencies of histone modifications along a promoter and leads to more interpretable results. We predict a general histone code that is independent of transcript orientation, cell type, and promoter configuration. The histone code at BDPs reveals that promoters are regulated unidirectionally, such that the majority of histone marks associated with gene expression occur downstream of the gene's TSS. By contrasting associations of histone marks with steady-state levels of capped RNAs in  CAGE and nascent capped RNAs in GRO-cap, we show which histone marks have a preference for initiating polymerases and actively elongating polymerases. Using single-cell data we show that the bidirectional histone signal of activating marks is often due averaging of a heterogeneous cell population. Our results have implications for other experiments where the  relationship between histone modification and gene initiation or gene elongation is investigated on a genome-wide scale.","abstract":"Recent studies indicate that thousands of genes are expressed from bidirectional promoters (BDPs). Gene regulation at BDPs is poorly understood, in particular how the cell is able to regulate them differently. Here we investigate the effect of histone Modifications in BDP regulation. In this study, we model the gene activity using different gene  expression assays, such as RNA-Seq, GRO-cap, and CAGE around the BDP transcription start sites (TSSs) using different histone modifications in various cell types. We develop a new statistical approach that links histone modifications to gene expression at BDPs. It improves over previous methods, because it is able to capture spatial dependencies of histone modifications along a promoter and leads to more interpretable results. We predict a general histone code that is independent of transcript orientation, cell type, and promoter configuration. The histone code at BDPs reveals that promoters are regulated unidirectionally, such that the majority of histone marks associated with gene expression occur downstream of the gene's TSS. By contrasting associations of histone marks with steady-state levels of capped RNAs in  CAGE and nascent capped RNAs in GRO-cap, we show which histone marks have a preference for initiating polymerases and actively elongating polymerases. Using single-cell data we show that the bidirectional histone signal of activating marks is often due averaging of a heterogeneous cell population. Our results have implications for other experiments where the  relationship between histone modification and gene initiation or gene elongation is investigated on a genome-wide scale.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-12-22T15:17:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001657","title":"Exome sequencing of retinoblastoma tumors","description":"Retinoblastoma is the most common intraocular cancer of infancy and childhood, with an incidence of one case per 15,000 - 20,000 live births. Patients in developed countries have a good prognosis. \n                However, in most cases, enucleation of the affected eye is required. In low- and middle-income countries, retinoblastoma is frequently lethal.\n                 A loss of function of both alleles of the RB1 gene is an early event in the development of retinoblastoma. \n                 However, other genes are also likely to be involved in the development of this cancer.\n                The long-term aim of our studies is to identify the additional events leading to retinoblastoma, whether genetic or epigenetic in nature, and to identify signaling pathways and therapeutic targets for this disease. \n                We will start by performing a multi-omics analysis of retinoblastomas of different stages from France, Argentina and Spain. \n                We will study the mutations (exome sequencing), genomic changes, transcriptome and methylome of 74 tumors. We will also investigate the transcriptome and methylome of the healthy retina. \n                Immunohistochemistry studies will then be carried out for key proteins identified in these analyses.\n                Correlations between molecular alterations and clinical features will be investigated and a validation study will be performed on an additional series of 40 samples.","abstract":"Retinoblastoma is the most common intraocular cancer of infancy and childhood, with an incidence of one case per 15,000 - 20,000 live births. Patients in developed countries have a good prognosis.                 However, in most cases, enucleation of the affected eye is required. In low- and middle-income countries, retinoblastoma is frequently lethal.                 A loss of function of both alleles of the RB1 gene is an early event in the development of retinoblastoma.                  However, other genes are also likely to be involved in the development of this cancer.                The long-term aim of our studies is to identify the additional events leading to retinoblastoma, whether genetic or epigenetic in nature, and to identify signaling pathways and therapeutic targets for this disease.                 We will start by performing a multi-omics analysis of retinoblastomas of different stages from France, Argentina and Spain.                 We will study the mutations (exome sequencing), genomic changes, transcriptome and methylome of 74 tumors. We will also investigate the transcriptome and methylome of the healthy retina.                 Immunohistochemistry studies will then be carried out for key proteins identified in these analyses.                Correlations between molecular alterations and clinical features will be investigated and a validation study will be performed on an additional series of 40 samples.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001658","title":"33 patients with Monoclonal Gammopathy of Undetermined Significance (MGUS) had whole exome sequencing performed.  Cells were sorted by FACSAria using CD138, CD19 and CD56 to obtain a pure abnormal plasma cell population.  Generated somatic variants were compared to a previous study of 463 multiple myeloma patients.","description":"Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant precursor of multiple myeloma (MM) with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS genes mutations, little is known about molecular mechanism of malignant transformation. We have performed whole exome sequencing together with SNP array analysis in 33 flow-cytometry separated abnormal PC samples of MGUS patients to describe somatic gene mutations and chromosome changes at the genome-wide level. Non-synonymous mutations (NS-SNVs) and copy number alterations (CNAs) were present in 97.0% and in 63.6% of cases, respectively. Importantly, the number of somatic mutations was significantly lower in MGUS compared to MM (p&lt;10-4) and we have identified 6 myeloma significantly mutated genes which are KRAS, NRAS, DIS3, HIST1H1E, EGR1 and LTB in the MGUS dataset. We also found a positive correlation with increasing chromosome changes and somatic mutations. IGH translocations were present in 27.3% of cases comprising t(4;14), t(11;14), t(14;16) or t(14;20) and were in a similar frequency to MM, which corresponded with primary lesion hypothesis. Data from this study showed MGUS is a genetically comprehensive disease, however overall genetic instability is significantly lower compared to MM.","abstract":"Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant precursor of multiple myeloma (MM) with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS genes mutations, little is known about molecular mechanism of malignant transformation. We have performed whole exome sequencing together with SNP array analysis in 33 flow-cytometry separated abnormal PC samples of MGUS patients to describe somatic gene mutations and chromosome changes at the genome-wide level. Non-synonymous mutations (NS-SNVs) and copy number alterations (CNAs) were present in 97.0% and in 63.6% of cases, respectively. Importantly, the number of somatic mutations was significantly lower in MGUS compared to MM (p&lt;10-4) and we have identified 6 myeloma significantly mutated genes which are KRAS, NRAS, DIS3, HIST1H1E, EGR1 and LTB in the MGUS dataset. We also found a positive correlation with increasing chromosome changes and somatic mutations. IGH translocations were present in 27.3% of cases comprising t(4;14), t(11;14), t(14;16) or t(14;20) and were in a similar frequency to MM, which corresponded with primary lesion hypothesis. Data from this study showed MGUS is a genetically comprehensive disease, however overall genetic instability is significantly lower compared to MM.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2015-12-28T16:25:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001659","title":"Integrated clinical, whole genome, and transcriptome analysis of multisampled lethal metastatic prostate cancer","description":"We report the first combined analysis of whole genome sequence, detailed clinical history, and transcriptome sequence of multiple prostate cancer metastases in a single patient (A21).  Whole genome and transcriptome sequence was obtained from 9 anatomically separate metastases, and targeted DNA sequencing was performed in cancerous and noncancerous foci within the primary tumor specimen removed 5 years prior to death. Transcriptome analysis revealed increased expression of AR-regulated genes in liver metastases that harbored an AR p.L702H mutation, suggesting a dominant effect by the mutation despite being present in only 1 of an estimated 16 copies per cell. The metastases harbored several alterations to the PI3K/AKT pathway, including a clonal truncal mutation in PIK3CG and present in all metastatic sites studied.  The list of truncal genomic alterations shared by all metastases included homozygous deletion of TP53, hemizygous deletion of RB1 and CHD1, and amplification of FGFR1. If the patient were treated today given this knowledge, use of second-generation androgen-directed therapies, cessation of glucocorticoid administration, and therapeutic inhibition of the PI3K/AKT pathway or FGFR1 receptor could provide personalized benefit. Three previously unreported truncal clonal missense mutations (ABCC4 p.R891L, ALDH9A1 p.W89R, and ASNA1 p.P75R) were expressed at the RNA level and assessed as druggable. The truncal status of mutations is critical for actionability, and can only be determined through analysis of multiple sites of metastasis. Our findings suggest that a large set of deeply analyzed cases could serve as powerful guide to more effective prostate cancer basic science and personalized cancer medicine clinical trials.","abstract":"We report the first combined analysis of whole genome sequence, detailed clinical history, and transcriptome sequence of multiple prostate cancer metastases in a single patient (A21).  Whole genome and transcriptome sequence was obtained from 9 anatomically separate metastases, and targeted DNA sequencing was performed in cancerous and noncancerous foci within the primary tumor specimen removed 5 years prior to death. Transcriptome analysis revealed increased expression of AR-regulated genes in liver metastases that harbored an AR p.L702H mutation, suggesting a dominant effect by the mutation despite being present in only 1 of an estimated 16 copies per cell. The metastases harbored several alterations to the PI3K/AKT pathway, including a clonal truncal mutation in PIK3CG and present in all metastatic sites studied.  The list of truncal genomic alterations shared by all metastases included homozygous deletion of TP53, hemizygous deletion of RB1 and CHD1, and amplification of FGFR1. If the patient were treated today given this knowledge, use of second-generation androgen-directed therapies, cessation of glucocorticoid administration, and therapeutic inhibition of the PI3K/AKT pathway or FGFR1 receptor could provide personalized benefit. Three previously unreported truncal clonal missense mutations (ABCC4 p.R891L, ALDH9A1 p.W89R, and ASNA1 p.P75R) were expressed at the RNA level and assessed as druggable. The truncal status of mutations is critical for actionability, and can only be determined through analysis of multiple sites of metastasis. Our findings suggest that a large set of deeply analyzed cases could serve as powerful guide to more effective prostate cancer basic science and personalized cancer medicine clinical trials.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-01-01T09:46:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001660","title":"160 WES and 25 WGS for HBV related HCC, and 15 WES for ICC","description":"Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. We performed whole-exome sequencing on 160 hepatitis B virus (HBV)-associated HCCs and matched non-tumor tissues. We also performed whole-genome sequencing on 25 hepatitis B virus (HBV)-associated HCCs and matched non-tumor tissues.","abstract":"Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. We performed whole-exome sequencing on 160 hepatitis B virus (HBV)-associated HCCs and matched non-tumor tissues. We also performed whole-genome sequencing on 25 hepatitis B virus (HBV)-associated HCCs and matched non-tumor tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001661","title":"Transcriptome Sequencing (RNAseq) enables utilization of Formalin-Fixed, Paraffin-Embedded Biopsies with Clear Cell Renal Cell Carcinoma for Exploration of Disease Biology and Biomarker Development","description":"Formalin-fixed, paraffin-embedded (FFPE) tissues are an underused resource for molecular analyses. This proof of concept study aimed to compare RNAseq results from FFPE biopsies with the corresponding RNAlater® (Qiagen, Germany) stored samples from clear cell renal cell carcinoma (ccRCC) patients to investigate feasibility of  RNAseq in archival tissue. From each of 16 patients undergoing partial or full nephrectomy, four core biopsies, such as two specimens with ccRCC and two specimens of adjacent normal tissue, were obtained with a 16g needle. One normal and one ccRCC tissue specimen per patient was stored either in FFPE or RNAlater®. RNA sequencing libraries were generated applying the new Illumina TruSeq® Access library preparation protocol.","abstract":"Formalin-fixed, paraffin-embedded (FFPE) tissues are an underused resource for molecular analyses. This proof of concept study aimed to compare RNAseq results from FFPE biopsies with the corresponding RNAlater® (Qiagen, Germany) stored samples from clear cell renal cell carcinoma (ccRCC) patients to investigate feasibility of  RNAseq in archival tissue. From each of 16 patients undergoing partial or full nephrectomy, four core biopsies, such as two specimens with ccRCC and two specimens of adjacent normal tissue, were obtained with a 16g needle. One normal and one ccRCC tissue specimen per patient was stored either in FFPE or RNAlater®. RNA sequencing libraries were generated applying the new Illumina TruSeq® Access library preparation protocol.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001662","title":"PANGEA","description":"Prevalence of HIV continues to be high in parts of Southern Africa. In the face of vaccine failures, and limited impact of behavioral interventions, much hope is pinned on combination strategies involving antiretroviral therapy. However, there remains a major challenge in developing tools to detect reductions in incidence, or providing insights into continual transmissions, particularly in generalized HIV-1 epidemic settings. Could viral phylogenetics play a role in describing the epidemic and in assessing the impact of interventions?Phylogenetics is the study of evolutionary relationships among groups of organisms. Phylogenetic analysis has played a crucial role in increasing our understanding of many aspects of HIV biology, including identification of the zoonotic origin of the virus and its migration across the planet.  In developed countries, the opportunities presented by large-scale sequence datasets generated through universal treatment monitoring have promoted development of methodology for their analysis to better characterize the transmission of HIV within these epidemics. Different modelling approaches have been adopted in UK, European and US settings with the aim of establishing direct links between epidemiological models of infectious disease and the interpretation of viral sequence data, but even in these data-rich settings there is no consensus on the optimum approach overall.The greatest challenge to the characterization of HIV transmission is the complexity of the networks along which it spreads. These differ between populations, between risk groups and between communities and to date only concentrated epidemics have been studied. The current study is the first to develop a coherent approach to extending these analyses to generalized epidemics. This represents a potential major advance in monitoring the impact of new interventions to reduce HIV-1 spread, including the expanded use of antiretrovirals. Further, we are assessing the utility of embedding such approaches in future trials of new interventions.The PANGEA_HIV project aims to adapt modern molecular epidemiology and phylodynamics of HIV sequence data to generate new insights into HIV transmission dynamics in generalized epidemics in Africa, and to provide a potential new approach for the evaluation of transmission interventions.http://www.pangea-hiv.org/http://www.sanger.ac.uk/science/collaboration/pangeaThese data are part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Prevalence of HIV continues to be high in parts of Southern Africa. In the face of vaccine failures, and limited impact of behavioral interventions, much hope is pinned on combination strategies involving antiretroviral therapy. However, there remains a major challenge in developing tools to detect reductions in incidence, or providing insights into continual transmissions, particularly in generalized HIV-1 epidemic settings. Could viral phylogenetics play a role in describing the epidemic and in assessing the impact of interventions?Phylogenetics is the study of evolutionary relationships among groups of organisms. Phylogenetic analysis has played a crucial role in increasing our understanding of many aspects of HIV biology, including identification of the zoonotic origin of the virus and its migration across the planet.  In developed countries, the opportunities presented by large-scale sequence datasets generated through universal treatment monitoring have promoted development of methodology for their analysis to better characterize the transmission of HIV within these epidemics. Different modelling approaches have been adopted in UK, European and US settings with the aim of establishing direct links between epidemiological models of infectious disease and the interpretation of viral sequence data, but even in these data-rich settings there is no consensus on the optimum approach overall.The greatest challenge to the characterization of HIV transmission is the complexity of the networks along which it spreads. These differ between populations, between risk groups and between communities and to date only concentrated epidemics have been studied. The current study is the first to develop a coherent approach to extending these analyses to generalized epidemics. This represents a potential major advance in monitoring the impact of new interventions to reduce HIV-1 spread, including the expanded use of antiretrovirals. Further, we are assessing the utility of embedding such approaches in future trials of new interventions.The PANGEA_HIV project aims to adapt modern molecular epidemiology and phylodynamics of HIV sequence data to generate new insights into HIV transmission dynamics in generalized epidemics in Africa, and to provide a potential new approach for the evaluation of transmission interventions.http://www.pangea-hiv.org/http://www.sanger.ac.uk/science/collaboration/pangea","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001663","title":"Population Structure and Genetic Diversity in Argentinean populations","description":"Argentina was one of the last places peopled when humans entered the Americas. Its earliest archeological sites are dated from 13,000 years BP, and throughout its history the region has exhibited broad cultural diversity, involving both hunter-gatherer and agro-pastoral societies, different linguistic families, the Southern expansion of the Inca Empire, the arrival of the Spanish conquistadors and slave trade from Africa. More recently, Argentina has had the highest proportion of influx of transoceanic migration between 1850 and 1940 of any Latin American country. Furthermore, the geographical distribution of immigrants was oriented towards the Pampa region of central-eastern Argentina and the Northeast, so different patterns of mixed ancestry throughout the country are expected. In this present work we aim to describe the history and structure of the Argentinean population. Thus far, we have collected DNA samples from 2904 participants from 15 dispersed regions in Argentina, from the Andean populations in the Northwest to the river lands of the Northeast. Our preliminary data includes genome-scale Illumina Exome Array 250K genotypes, plus next-generation sequencing data from uniformly spaced genomic regions targeted with a genotype-by- sequencing strategy (which covers 1.5% of the genome), for 375 participants from 9 of the 15 populations. We will identify proportions and patterns of European, African and Indigenous American ancestry in the Argentinean cohort via local ancestry inference. The first series of analyses will focus on genomic tracts of Indigenous American ancestry for fine-scale examination of sub-continental structure by comparing to a panel of 493 samples from 52 Indigenous American populations from throughout the Americas. Furthermore, this work will serve as a test of different low-cost strategies (exome genotype array vs. genotype-by-sequencing) for accurate inference of population structure in extant populations.","abstract":"Argentina was one of the last places peopled when humans entered the Americas. Its earliest archeological sites are dated from 13,000 years BP, and throughout its history the region has exhibited broad cultural diversity, involving both hunter-gatherer and agro-pastoral societies, different linguistic families, the Southern expansion of the Inca Empire, the arrival of the Spanish conquistadors and slave trade from Africa. More recently, Argentina has had the highest proportion of influx of transoceanic migration between 1850 and 1940 of any Latin American country. Furthermore, the geographical distribution of immigrants was oriented towards the Pampa region of central-eastern Argentina and the Northeast, so different patterns of mixed ancestry throughout the country are expected. In this present work we aim to describe the history and structure of the Argentinean population. Thus far, we have collected DNA samples from 2904 participants from 15 dispersed regions in Argentina, from the Andean populations in the Northwest to the river lands of the Northeast. Our preliminary data includes genome-scale Illumina Exome Array 250K genotypes, plus next-generation sequencing data from uniformly spaced genomic regions targeted with a genotype-by- sequencing strategy (which covers 1.5% of the genome), for 375 participants from 9 of the 15 populations. We will identify proportions and patterns of European, African and Indigenous American ancestry in the Argentinean cohort via local ancestry inference. The first series of analyses will focus on genomic tracts of Indigenous American ancestry for fine-scale examination of sub-continental structure by comparing to a panel of 493 samples from 52 Indigenous American populations from throughout the Americas. Furthermore, this work will serve as a test of different low-cost strategies (exome genotype array vs. genotype-by-sequencing) for accurate inference of population structure in extant populations.","study_type":"Other","pubmed_ids":[26828719],"external_links":null,"is_released":true,"released_date":"2016-01-06T22:16:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001664","title":"Investigating_the_genetics_of_immunity_against_Salmonella_in_humans","description":"This study entails whole genome sequencing of an interleukin (IL)-12 b-1 receptor-deficient individual who presented with a chronic systemic Salmonella Enteritidis infection that did not resolve with standard IFNg and antibiotic treatment. Whole genome sequencing of the patient’s parents are also included.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This study entails whole genome sequencing of an interleukin (IL)-12 b-1 receptor-deficient individual who presented with a chronic systemic Salmonella Enteritidis infection that did not resolve with standard IFNg and antibiotic treatment. Whole genome sequencing of the patient’s parents are also included.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-01-07T10:46:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001665","title":"Rare SNPs in receptor tyrosine kinases are negative outcome predictors in multiple myeloma","description":"Multiple myeloma (MM) is a plasma cell disorder that is characterized by a great genetic heterogeneity. Recent next generation sequencing studies revealed an accumulation of tumor-associated mutations in receptor tyrosine kinases (RTKs) which may also contribute to the activation of survival pathways in MM. To investigate the clinical role of RTK-mutations in MM, we deep-sequenced the coding DNA-sequence of EGFR, EPHA2, ERBB3, IGF1R, NTRK1 and NTRK2 which were previously found to be mutated in MM, in 75 uniformly treated MM patients of the \"Deutsche Studiengruppe Multiples Myelom\". Subsequently, we correlated the detected mutations with common cytogenetic alterations and clinical parameters. We identified 11 novel non-synonymous SNVs or rare patient-specific SNPs, not listed in the SNP databases 1000 genomes and dbSNP, in 10 primary MM cases. The mutations predominantly affected the tyrosine-kinase and ligand-binding domains and no correlation with cytogenetic parameters was found. Interestingly, however, patients with RTK-mutations, specifically those with rare patient-specific SNPs, showed a significant lower overall, event-free and progression-free survival. This indicates that RTK SNVs and rare patient-specific RTK SNPs are of prognostic relevance and suggests that MM patients with RTK-mutations could potentially profit from treatment with RTK-inhibitors.","abstract":"Multiple myeloma (MM) is a plasma cell disorder that is characterized by a great genetic heterogeneity. Recent next generation sequencing studies revealed an accumulation of tumor-associated mutations in receptor tyrosine kinases (RTKs) which may also contribute to the activation of survival pathways in MM. To investigate the clinical role of RTK-mutations in MM, we deep-sequenced the coding DNA-sequence of EGFR, EPHA2, ERBB3, IGF1R, NTRK1 and NTRK2 which were previously found to be mutated in MM, in 75 uniformly treated MM patients of the \"Deutsche Studiengruppe Multiples Myelom\". Subsequently, we correlated the detected mutations with common cytogenetic alterations and clinical parameters. We identified 11 novel non-synonymous SNVs or rare patient-specific SNPs, not listed in the SNP databases 1000 genomes and dbSNP, in 10 primary MM cases. The mutations predominantly affected the tyrosine-kinase and ligand-binding domains and no correlation with cytogenetic parameters was found. Interestingly, however, patients with RTK-mutations, specifically those with rare patient-specific SNPs, showed a significant lower overall, event-free and progression-free survival. This indicates that RTK SNVs and rare patient-specific RTK SNPs are of prognostic relevance and suggests that MM patients with RTK-mutations could potentially profit from treatment with RTK-inhibitors.","study_type":"Other","pubmed_ids":[23396385,25521164],"external_links":null,"is_released":true,"released_date":"2016-01-07T12:31:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001666","title":"Large scale familial CRC exome sequencing study","description":"The burden of rare disruptive mutations to the heritable risk of colorectal cancer","abstract":"The burden of rare disruptive mutations to the heritable risk of colorectal cancer","study_type":"Other","pubmed_ids":[27329137],"external_links":null,"is_released":true,"released_date":"2016-01-08T14:44:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001667","title":"ICR MOPOPGEN UK exome control series","description":"ICR MOPOPGEN UK exome control series","abstract":"ICR MOPOPGEN UK exome control series","study_type":"Other","pubmed_ids":[27329137],"external_links":null,"is_released":true,"released_date":"2016-01-08T14:47:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001668","title":"C14orf93 (RTFC) is Identified as a Novel Regulator for Familial Nonmedullary Thyroid Cancer and Thyroid Function","description":"The genetic causes for familial nonmedullary thyroid cancer (FNMTC) remain largely unknown. Through genetic linkage analysis and exome sequencing, C14orf93 (RTFC) was identified as a novel susceptibility gene in a FNMTC family. RTFC promotes thyroid cancer cell survival under starving conditions, and thyroid cancer cell migration. The FNMTC-linked V205M RTFC mutant enhances the colony forming capacity of thyroid cancer cells. Moreover, knockout of Rtfc compromises the in vitro thyroid differentiation of mouse ESCs. Rtfc-/- mice are viable and fertile, and the size and the morphology of thyroid are not affected by Rtfc knockout. However, female Rtfc-/- mice, but not male Rtfc-/- mice, display hypothyroidism. In summary, our data suggest the roles of RTFC in thyroid carcinogenesis, in vitro differentiation of thyroid cells, and in vivo thyroid function.","abstract":"The genetic causes for familial nonmedullary thyroid cancer (FNMTC) remain largely unknown. Through genetic linkage analysis and exome sequencing, C14orf93 (RTFC) was identified as a novel susceptibility gene in a FNMTC family. RTFC promotes thyroid cancer cell survival under starving conditions, and thyroid cancer cell migration. The FNMTC-linked V205M RTFC mutant enhances the colony forming capacity of thyroid cancer cells. Moreover, knockout of Rtfc compromises the in vitro thyroid differentiation of mouse ESCs. Rtfc-/- mice are viable and fertile, and the size and the morphology of thyroid are not affected by Rtfc knockout. However, female Rtfc-/- mice, but not male Rtfc-/- mice, display hypothyroidism. In summary, our data suggest the roles of RTFC in thyroid carcinogenesis, in vitro differentiation of thyroid cells, and in vivo thyroid function.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001669","title":"Rare SNPs in receptor tyrosine kinases are negative outcome predictors in multiple myeloma","description":"Multiple myeloma (MM) is a plasma cell disorder that is characterized by a great genetic heterogeneity. Recent next generation sequencing studies revealed an accumulation of tumor-associated mutations in receptor tyrosine kinases (RTKs) which may also contribute to the activation of survival pathways in MM. To investigate the clinical role of RTK-mutations in MM, we deep-sequenced the coding DNA-sequence of EGFR, EPHA2, ERBB3, IGF1R, NTRK1 and NTRK2 which were previously found to be mutated in MM, in 75 uniformly treated MM patients of the \"Deutsche Studiengruppe Multiples Myelom\". Subsequently, we correlated the detected mutations with common cytogenetic alterations and clinical parameters. We identified 11 novel non-synonymous SNVs or rare patient-specific SNPs, not listed in the SNP databases 1000 genomes and dbSNP, in 10 primary MM cases. The mutations predominantly affected the tyrosine-kinase and ligand-binding domains and no correlation with cytogenetic parameters was found. Interestingly, however, patients with RTK-mutations, specifically those with rare patient-specific SNPs, showed a significant lower overall, event-free and progression-free survival. This indicates that RTK SNVs and rare patient-specific RTK SNPs are of prognostic relevance and suggests that MM patients with RTK-mutations could potentially profit from treatment with RTK-inhibitors.","abstract":"Multiple myeloma (MM) is a plasma cell disorder that is characterized by a great genetic heterogeneity. Recent next generation sequencing studies revealed an accumulation of tumor-associated mutations in receptor tyrosine kinases (RTKs) which may also contribute to the activation of survival pathways in MM. To investigate the clinical role of RTK-mutations in MM, we deep-sequenced the coding DNA-sequence of EGFR, EPHA2, ERBB3, IGF1R, NTRK1 and NTRK2 which were previously found to be mutated in MM, in 75 uniformly treated MM patients of the \"Deutsche Studiengruppe Multiples Myelom\". Subsequently, we correlated the detected mutations with common cytogenetic alterations and clinical parameters. We identified 11 novel non-synonymous SNVs or rare patient-specific SNPs, not listed in the SNP databases 1000 genomes and dbSNP, in 10 primary MM cases. The mutations predominantly affected the tyrosine-kinase and ligand-binding domains and no correlation with cytogenetic parameters was found. Interestingly, however, patients with RTK-mutations, specifically those with rare patient-specific SNPs, showed a significant lower overall, event-free and progression-free survival. This indicates that RTK SNVs and rare patient-specific RTK SNPs are of prognostic relevance and suggests that MM patients with RTK-mutations could potentially profit from treatment with RTK-inhibitors.","study_type":"Other","pubmed_ids":[23396385,25521164],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001670","title":"Ancient_African_Genomes__South_Africa","description":"We plan to sequence on the Illumina Hiseq platform ancient whole genomes from several libraries prepared from ancient bone samples collected from archeological sites and museum collections in Africa incuding South Africa and Lesotho. DNA extraction and library preparation will be carried out externally by our collaborators. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Analyses of ancient DNA complement sequencing of modern human populations and provide unique opportunities to transform our understanding of human pre-history. Despite extensive efforts focused on identifying populations and migration patterns out of Africa, the genetic structure and geographical distribution of ancient and pre-historical populations within Africa remain unclear—including the patterns of divergence of hunter gatherer populations across Africa. An approach combining ancient DNA and modern genomes would greatly refine our understanding of population structure and movements, including genetic signatures of ancient admixture, within these continents and globally. Additionally, using ancient DNA to track the trajectories of allele frequencies over time would also allow a direct study of adaptation to selective forces.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001671","title":"Ancient_African_Genomes__Lesotho","description":"We plan to sequence on the Illumina Hiseq platform ancient whole genomes from several libraries prepared from ancient bone samples collected from archeological sites and museum collections in Africa incuding South Africa and Lesotho. DNA extraction and library preparation will be carried out externally by our collaborators. \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Analyses of ancient DNA complement sequencing of modern human populations and provide unique opportunities to transform our understanding of human pre-history. Despite extensive efforts focused on identifying populations and migration patterns out of Africa, the genetic structure and geographical distribution of ancient and pre-historical populations within Africa remain unclear—including the patterns of divergence of hunter gatherer populations across Africa. An approach combining ancient DNA and modern genomes would greatly refine our understanding of population structure and movements, including genetic signatures of ancient admixture, within these continents and globally. Additionally, using ancient DNA to track the trajectories of allele frequencies over time would also allow a direct study of adaptation to selective forces.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001672","title":"This is a test","description":"This is an abstract of the test study","abstract":"This is an abstract of the test study","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001673","title":"The_RNAseq_analysis_of_human_iPS_derived_macrophages_infected_with_either_capsulated_or_non_capsulated_Klebsiella_pnuemoniae","description":"Klebsiella pneumoniae is a gram-negative pathogen which can cause a wide range of infections from urinary tractinfections to pneumonia and is considered a major threat to public health. While commensal carriage (e.g. skin andnasopharynx and gastrointestinal tract) is common, Klebsiella can become pathogenic in individuals withcompromised immunity.  It is a leading cause of hospital-acquired infections, commonly presenting as pneumonia,urinary tract infection and sepsis.  In addition, Klebsiella also causes community-acquired infections with seriouscomplications, such as liver abscess and meningitis.  Despite the disease burden and escalating prevalence of multi-drug resistance, not much is known about the initial interaction between the bacterial and host cells, presenting anunder-exploited opportunity for therapeutic and/or prophylactic interventions targeting the early stage of pathogenencounter.A key determinant of Klebsiella’s pathogenicity is the thick outer layer of polysaccharide known as the capsule.  It hasbeen suggested that variation in the Klebsiella capsular serotype impacts on its internalisation by epithelial cells andmacrophages, however, critical details of cellular and molecular factors remain incompletely understood. We haveinitiated in vitro studies using both capsulated and non-capsulated engineered forms of Klebsiella pnuemoniae toinfect macrophages derived from differentiated human induced pluripotent stem cells. The aim of our study is toanalyse the global host response in an attempt to establish transcriptional signatures that can be used for predictingdisease severity or outcome.  If this approach proves effective, the next step will be to use this system with a carefulselection of Klebsiella clinical isolates that encompasses all three (sub)species (KpI, KpII and KpIII) and includevariations in capsular serovars, infected site and community versus hospital acquired infections.We would like to request funds to sequence replicates of the RNA from capsulated and non-capsulated Klebsiellainfected macrophages at a fixed time point of infectionThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Klebsiella pneumoniae is a gram-negative pathogen which can cause a wide range of infections from urinary tractinfections to pneumonia and is considered a major threat to public health. While commensal carriage (e.g. skin andnasopharynx and gastrointestinal tract) is common, Klebsiella can become pathogenic in individuals withcompromised immunity.  It is a leading cause of hospital-acquired infections, commonly presenting as pneumonia,urinary tract infection and sepsis.  In addition, Klebsiella also causes community-acquired infections with seriouscomplications, such as liver abscess and meningitis.  Despite the disease burden and escalating prevalence of multi-drug resistance, not much is known about the initial interaction between the bacterial and host cells, presenting anunder-exploited opportunity for therapeutic and/or prophylactic interventions targeting the early stage of pathogenencounter.A key determinant of Klebsiella’s pathogenicity is the thick outer layer of polysaccharide known as the capsule.  It hasbeen suggested that variation in the Klebsiella capsular serotype impacts on its internalisation by epithelial cells andmacrophages, however, critical details of cellular and molecular factors remain incompletely understood. We haveinitiated in vitro studies using both capsulated and non-capsulated engineered forms of Klebsiella pnuemoniae toinfect macrophages derived from differentiated human induced pluripotent stem cells. The aim of our study is toanalyse the global host response in an attempt to establish transcriptional signatures that can be used for predictingdisease severity or outcome.  If this approach proves effective, the next step will be to use this system with a carefulselection of Klebsiella clinical isolates that encompasses all three (sub)species (KpI, KpII and KpIII) and includevariations in capsular serovars, infected site and community versus hospital acquired infections.We would like to request funds to sequence replicates of the RNA from capsulated and non-capsulated Klebsiellainfected macrophages at a fixed time point of infection","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001674","title":"Genome_wide_association_study_of_vaccine_responses_in_infants_living_in_the_Developing_World__VaccGene___PROVIDE_cohort__Bangladesh_","description":"It is estimated that up to 70% of the variability in response to some vaccines administered in childhood is inherited but the identification of the genetic factors responsible for this variation has not yet been prioritised. We have set up one of the largest genome-wide association studies of vaccine responses ever undertaken, which will provide unparalleled power to identify the genetic factors associated with the response to all of the most commonly used childhood vaccines worldwide. This dataset refers to the PROVIDE cohort from Bangladesh.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"It is estimated that up to 70% of the variability in response to some vaccines administered in childhood is inherited but the identification of the genetic factors responsible for this variation has not yet been prioritised. We have set up one of the largest genome-wide association studies of vaccine responses ever undertaken, which will provide unparalleled power to identify the genetic factors associated with the response to all of the most commonly used childhood vaccines worldwide. This dataset refers to the PROVIDE cohort from Bangladesh.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001675","title":"Amplicon_based_sequencing_of_drug_resistant_lung_cancer_cell_lines","description":"A EGFR mutant NSCLC cell line which is sensitive to AZD9291 inhibition was mutagenised with the chemical mutagen ENU and then drug selected using a AZD9291. Single cell derived colonies were then manually picked and expanded in drug. Resistance was confirmed in a 14 day assay and DNA was collected. These then underwent targeted amplicon-based sequencing to confirm candidate resistance effectors hypothesised from currently available literature.","abstract":"A EGFR mutant NSCLC cell line was mutagenised with the chemical mutagen ENU and then drug selected. Single cell derived colonies were then manually picked and expanded in drug. Resistance was confirmed and DNA was collected. These then underwent targeted amplicon-based sequencing. Pools of resistant clones were also sequenced.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-01-13T14:33:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001676","title":"Clonal_architecture_of_pre_malignant_and_malignant_tumours","description":"Single cells have been isolated from normal and pre-invasive lung cancer lesions from one patient. These have been grown into colonies that will then be whole genome sequenced. This will reveal the mutational burden in normal and premalignant tissues, and the heterogeneity between different cells.","abstract":"Single cells have been isolated from normal and pre-invasive lung cancer lesions from one patient. These have been grown into colonies that will then be whole genome sequenced. This will reveal the mutational burden in normal and premalignant tissues, and the heterogeneity between different cells.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-01-15T14:42:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001677","title":"Summary statistics from The Malaria Genetic Epidemiology Network, A novel locus of resistance to severe malaria in a region of ancient balancing selection, Nature (2015); doi:10.1038/nature15390.","description":"The high prevalence of sickle haemoglobin in Africa shows that malaria has been a major force for human evolutionary selection, but surprisingly few other polymorphisms have been proven to confer resistance to malaria in large epidemiological studies. To address this problem, we conducted a multi-centre genome-wide association study (GWAS) of life-threatening Plasmodium falciparum infection (severe malaria) in over 11,000 African children, with replication data in a further 14,000 individuals. Here we report a novel malaria resistance locus close to a cluster of genes encoding glycophorins that are receptors for erythrocyte invasion by P. falciparum. We identify a haplotype at this locus that provides 33% protection against severe malaria (odds ratio = 0.67, 95% confidence interval = 0.60–0.76, P value = 9.5 × 10−11) and is linked to polymorphisms that have previously been shown to have features of ancient balancing selection, on the basis of haplotype sharing between humans and chimpanzees4. Taken together with previous observations on the malaria-protective role of blood group O, these data reveal that two of the strongest GWAS signals for severe malaria lie in or close to genes encoding the glycosylated surface coat of the erythrocyte cell membrane, both within regions of the genome where it appears that evolution has maintained diversity for millions of years. These findings provide new insights into the host–parasite interactions that are critical in determining the outcome of malaria infection.","abstract":"The high prevalence of sickle haemoglobin in Africa shows that malaria has been a major force for human evolutionary selection, but surprisingly few other polymorphisms have been proven to confer resistance to malaria in large epidemiological studies. To address this problem, we conducted a multi-centre genome-wide association study (GWAS) of life-threatening Plasmodium falciparum infection (severe malaria) in over 11,000 African children, with replication data in a further 14,000 individuals. Here we report a novel malaria resistance locus close to a cluster of genes encoding glycophorins that are receptors for erythrocyte invasion by P. falciparum. We identify a haplotype at this locus that provides 33% protection against severe malaria (odds ratio = 0.67, 95% confidence interval = 0.60–0.76, P value = 9.5 × 10−11) and is linked to polymorphisms that have previously been shown to have features of ancient balancing selection, on the basis of haplotype sharing between humans and chimpanzees4. Taken together with previous observations on the malaria-protective role of blood group O, these data reveal that two of the strongest GWAS signals for severe malaria lie in or close to genes encoding the glycosylated surface coat of the erythrocyte cell membrane, both within regions of the genome where it appears that evolution has maintained diversity for millions of years. These findings provide new insights into the host–parasite interactions that are critical in determining the outcome of malaria infection.","study_type":"Other","pubmed_ids":[26416757],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001678","title":"Comparison of HCC cell lines and primary HCCs","description":"There are concerns about whether cancer cell lines could faithfully represent the matched primary cancer cells. Comparison of the HCC cell lines and primary HCCs demonstrated that, during long-term in vitro culture, cell lines retain the genetic landscape of the matched primary HCCs.","abstract":"There are concerns about whether cancer cell lines could faithfully represent the matched primary cancer cells. Comparison of the HCC cell lines and primary HCCs demonstrated that, during long-term in vitro culture, cell lines retain the genetic landscape of the matched primary HCCs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-01-19T04:04:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001679","title":"Genome_Diversity_in_Africa_Project__Mali","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region.The Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformaticsThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001680","title":"Transcriptomes_of_intestinal_organoids","description":"RNAseq of intestinal organoids from patients with IBD and healthy controls.The aim of the study is to address the role of IL22, a cytokine that has been associated with susceptibility to IBD, and its pathway on human epithelium from both control and IBD individuals. Human primary organoids were cultured in normal growth media and treated with varying concentrations of IL22.  At the designated time points RNA was extracted using the Qiagen AllPrep kit. Total RNA from each sample was used as input for the Illumina TruSeq Stranded messenger RNA LT Sample Prep Kit (Illumina) and sequencing libraries were created according to the manufacturer's protocol. Briefly, poly-A containing mRNA molecules were purified using poly-T oligo-attached magnetic beads. Following purification, the mRNA was fragmented and copied into first strand complementary DNA using random primers and reverse transcriptase. Second strand cDNA synthesis was performed using DNA polymerase I, RNase H and substituting dUTP for dTTP. The cDNA was ligated to adapters and enriched with PCR to create the final cDNA library. The library was pooled and 75 bp paired end  sequencing was performed using an Illumina HiSeq 2000. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The purpose of this study is to establish whether intestinal organoid cultures from IBD patients are a good model of disease by studying  various disease phenomena including, epithelial repair, wound healing, fibrotic changes, granulomas and inflammatory processes. Organoids will be used for target pertubation and validation studies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001681","title":"Nucleosome density ChIP-seq identifies distinct chromatin modification signatures of promoters associated with MNase accessibility","description":"Nucleosome position, density and posttranslational modifications are components of the mechanisms regulating gene expression. Here, we describe a modified native ChIP-seq method applicable to small input cell numbers that integrates MNase accessibility with histone modification profiles. Use of this methodology to generate H3K4me3 and H3K27me3 immunoprecipitated DNA fragment size distributions from a rare subset (CD34+) of normal human cord blood cells, enabled an analysis of DNA regions enriched in single versus two nucleosomes and their associated chromatin and methylation states. We defined 4 classes of promoter-specific profiles that effectively segregated apparent bivalently marked promoters into those heterogeneously marked and a smaller subset likely to be bivalent promoters at the single cell level. Extension of this approach to human embryonic stem cells revealed an altered relationship between the chromatin state and nucleosome content of their promoters compared to human CD34+ cord blood cells.","abstract":"Nucleosome position, density and posttranslational modifications are components of the mechanisms regulating gene expression. Here, we describe a modified native ChIP-seq method applicable to small input cell numbers that integrates MNase accessibility with histone modification profiles. Use of this methodology to generate H3K4me3 and H3K27me3 immunoprecipitated DNA fragment size distributions from a rare subset (CD34+) of normal human cord blood cells, enabled an analysis of DNA regions enriched in single versus two nucleosomes and their associated chromatin and methylation states. We defined 4 classes of promoter-specific profiles that effectively segregated apparent bivalently marked promoters into those heterogeneously marked and a smaller subset likely to be bivalent promoters at the single cell level. Extension of this approach to human embryonic stem cells revealed an altered relationship between the chromatin state and nucleosome content of their promoters compared to human CD34+ cord blood cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001682","title":"Tissue-specific mutation accumulation in human adult stem cells during life","description":"Gradual accumulation of mutations in human adult stem cells during life is associated with various age-related diseases, including cancer. The number of stem cell divisions throughout life is believed to be a major determinant for mutation accumulation and could explain the extreme variation of cancer incidence across different organs. Yet, mutation patterns and rates of healthy adult stem cells remain unknown. Here, we determined genome-wide mutation patterns in primary adult stem cells of the small intestine, colon and liver of human donors with ages ranging from 3 to 87 years. We find that the number of mutations increases linearly with age up to several thousand mutations per cell at 87 years of age, while mutation spectra remain constant throughout life. Small intestine and colon stem cells have a 2-fold higher mutation rate per year compared with liver stem cells. These differences could be exclusively attributed to the mutagenic action of spontaneous deamination of cytosine residues and may reflect the high stem cell division rate in these tissues. The genomic distribution of somatic mutations is non-random and predominantly associated with DNA replication dynamics in the small intestine and colon, and with transcription in the liver. These results indicate that a stable balance between various mutagenic and DNA repair processes is maintained throughout life and that the activity of these processes in adult stem cells varies between tissues.","abstract":"Gradual accumulation of mutations in human adult stem cells during life is associated with various age-related diseases, including cancer. The number of stem cell divisions throughout life is believed to be a major determinant for mutation accumulation and could explain the extreme variation of cancer incidence across different organs. Yet, mutation patterns and rates of healthy adult stem cells remain unknown. Here, we determined genome-wide mutation patterns in primary adult stem cells of the small intestine, colon and liver of human donors with ages ranging from 3 to 87 years. We find that the number of mutations increases linearly with age up to several thousand mutations per cell at 87 years of age, while mutation spectra remain constant throughout life. Small intestine and colon stem cells have a 2-fold higher mutation rate per year compared with liver stem cells. These differences could be exclusively attributed to the mutagenic action of spontaneous deamination of cytosine residues and may reflect the high stem cell division rate in these tissues. The genomic distribution of somatic mutations is non-random and predominantly associated with DNA replication dynamics in the small intestine and colon, and with transcription in the liver. These results indicate that a stable balance between various mutagenic and DNA repair processes is maintained throughout life and that the activity of these processes in adult stem cells varies between tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-01-20T11:31:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001683","title":"Squamous_cell_carcinoma___Sequeira","description":"Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with a 5-year survival rate of only 50%. Recent whole exome sequencing of human HNSCC has highlighted the heterogeneity of the underlying genetic lesions (Agrawal et al., 2011; Stransky et al., 2011). One of the most intriguing findings from whole exome sequencing is the high frequency of inactivating mutations in NOTCH1. The aim of our project is to unravel at what stage in tumour development the epithelium acquires the p53, Notch, Caspase 8 and FAT1 mutations, that are a hallmark of the human cancer, and the impact on different cell types, using a mouse model of carcinogen induced oral SCC. Furthermore, identifying epithelial and stromal alterations that reflect genetic mutations will provide indicators offering an exciting strategy for diagnosis and treatment of cancer.","abstract":"Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with a 5-year survival rate of only 50%. Recent whole exome sequencing of human HNSCC has highlighted the heterogeneity of the underlying genetic lesions (Agrawal et al., 2011; Stransky et al., 2011). One of the most intriguing findings from whole exome sequencing is the high frequency of inactivating mutations in NOTCH1. The aim of our project is to unravel at what stage in tumour development the epithelium acquires the p53, Notch, Caspase 8 and FAT1 mutations, that are a hallmark of the human cancer, and the impact on different cell types, using a mouse model of carcinogen induced oral SCC. Furthermore, identifying epithelial and stromal alterations that reflect genetic mutations will provide indicators offering an exciting strategy for diagnosis and treatment of cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001684","title":"IBD_GWAS_2016","description":"As part of our ongoing follow-up of IBD sequencing and previous GWAS experiments, we have identified an additional 1200 samples from the UKIBDGC. We propose to GWAS these to add them to our existing and planned analyses.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"GWAS of patients with inflammatory bowel disease recruited from around the UK","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001685","title":"Sepsis_GWAS","description":"Severe sepsis genomics   A cohort of 978 patients admitted to intensive care units (ICUs) with severe sepsis have been recruited to date to the UK Genomic Advances in Sepsis (GAinS) study for functional genomic profiling to understand the sepsis response and reasons for inter-individual patient heterogeneity (PI Professor Julian Knight, Oxford). This includes 619 patients with severe sepsis due to community acquired pneumonia and 359 with severe sepsis due to faecal peritonitis. Comprehensive clinical phenotyping and microbiology was recorded including at up to 6 months following hospital discharge. The 28-day mortality was 21%. Blood samples were taken on admission, on day 3 and on day 5 following ICU admission where possible. Peripheral blood leukocytes were isolated and stored for RNA extraction with high quality RNA obtained (average RIN 8.0); genomic DNA was extracted; buffy coats, plasma and urine samples were stored for each patient. Transcriptomic profiling by microarray has been performed for 478 patients (Illumina Human HT12v4 Expression Beadchips) and genotyping for 295 patients (Illumina HumanOmniExpress BeadChips). Using this data, analysis has revealed transcriptomic signatures of severe sepsis informative for understanding disease heterogeneity and outcome; and expression quantitative trait mapping demonstrates sepsis specific eQTL. Here, we propose genotyping the remaining samples (683 patients).                                                                                                                                                                     We would aim to separately complement this by performing RNA-seq of available RNA samples to allow comprehensive transcriptomic profiling including over time, definition of the role of noncoding RNAs in the sepsis response, integration with genotyping data for better powered eQTL mapping and analysis of allele-specific expression; and to integrate with further epigenetic profiling of available samples including DNA methylation and microRNA profiling, proteomics and metablomics.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"A cohort of 978 patients admitted to intensive care units (ICUs) with severe sepsis have been recruited to date to the UK Genomic Advances in Sepsis (GAinS) study for functional genomic profiling to understand the sepsis response and reasons for inter-individual patient heterogeneity (PI Professor Julian Knight, Oxford). This includes 619 patients with severe sepsis due to community acquired pneumonia and 359 with severe sepsis due to faecal peritonitis","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001686","title":"Paired exome analysis in urothelial carcinoma","description":"In this study we characterized genomic alterations in two to five metachronous tumors from 29 patients initially diagnosed with early stage disease. Fourteen patients (32 tumors) had non progressive disease (NPD) and 15 patients (34 tumors) had progressive disease (PD). Whole exome sequencing (WES, ~50x mean read depth), Ultra deep targeted sequencing (~6,809x mean read depth) and whole transcriptome RNA-seq was performed for all samples. In addition multiregional WES was performed on 8 adjacent regions from a single tumor.","abstract":"In this study we characterized genomic alterations in two to five metachronous tumors from 29 patients initially diagnosed with early stage disease. Fourteen patients (32 tumors) had non progressive disease (NPD) and 15 patients (34 tumors) had progressive disease (PD). Whole exome sequencing (WES, ~50x mean read depth), Ultra deep targeted sequencing (~6,809x mean read depth) and whole transcriptome RNA-seq was performed for all samples. In addition multiregional WES was performed on 8 adjacent regions from a single tumor.","study_type":"Other","pubmed_ids":[27488526],"external_links":null,"is_released":true,"released_date":"2016-01-21T13:37:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001687","title":"Clonal_expansion_of_mutated_cell_population_in_bladder_urothelium_","description":"1cm biospies of from patients undergoing bladder cystectomy will be collected.  The underlying muscle and stroma will be removed and the remaining epithelia dissected into small sequential areas which will be sent for ultra-deep exome sequencing using a panel of known cancer and viral genes.  Sequence analysis using similar methods to Martincorena I et al (Science 2015, 348:880) will provide an idea of the  somatic mutational landscape in these patient samples.  Individual patient muscle samples will also be sequenced as a reference.","abstract":"The work will give an understanding of the somtaic mutational burden of bladder urothelia in patients undergoing cystectomy.  Biospies from discrete sites across the baldder will provide an idea of the mutational landscape across the epithelia and potentially give insights into the high incidence of recurrence in bladder carcinoma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-01-22T08:38:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001688","title":"Genome_Diversity_in_Africa_Project__Benin","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region.The Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformaticsThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-01-25T10:46:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001689","title":"Flemish_Gut_Flora_Project","description":"\"Here, we studied well-phenotyped individuals from the Flemish Gut Flora Project (FGFP, N=1,106, Belgium) and the effect of environments on microbiome.\"","abstract":"\"Here, we studied well-phenotyped individuals from the Flemish Gut Flora Project (FGFP, N=1,106, Belgium) and the effect of environments on microbiome.\"","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-01-25T14:31:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001690","title":"Whole exome sequencing on primary retinoblastoma tissues and matching lymphocyte DNA.","description":"Retinoblastoma is a rare childhood cancer initiated by RB1 mutation or MYCN amplification, while additional alterations may be required for tumor development. However, the view on single nucleotide variants is very limited. To better understand oncogenesis, we determined the genomic landscape of retinoblastoma.  We performed exome sequencing of 71 retinoblastomas and matched blood DNA. Next, we determined the presence of single nucleotide variants, copy number alterations and viruses.   Aside from RB1, recurrent gene mutations were very rare. Only a limited fraction of tumors showed BCOR (7/71, 10%) or CREBBP alterations (3/71, 4%). No evidence was found for the presence of viruses. Instead, specific somatic copy number alterations were more common, particularly in patients diagnosed at later age. Recurrent alterations of chromosomal arms often involved less than one copy, also in highly pure tumor samples, suggesting within-tumor heterogeneity.  Our results show that retinoblastoma is among the least mutated cancers and signify the extreme sensitivity of the childhood retina for RB1 loss. We hypothesize that retinoblastomas arising later in retinal development benefit more from subclonal secondary alterations and therefore, these alterations are more selected for in these tumors. Targeted therapy based on these subclonal events might be insufficient for complete tumor control.","abstract":"Retinoblastoma is a rare childhood cancer initiated by RB1 mutation or MYCN amplification, while additional alterations may be required for tumor development. However, the view on single nucleotide variants is very limited. To better understand oncogenesis, we determined the genomic landscape of retinoblastoma.  We performed exome sequencing of 71 retinoblastomas and matched blood DNA. Next, we determined the presence of single nucleotide variants, copy number alterations and viruses.   Aside from RB1, recurrent gene mutations were very rare. Only a limited fraction of tumors showed BCOR (7/71, 10%) or CREBBP alterations (3/71, 4%). No evidence was found for the presence of viruses. Instead, specific somatic copy number alterations were more common, particularly in patients diagnosed at later age. Recurrent alterations of chromosomal arms often involved less than one copy, also in highly pure tumor samples, suggesting within-tumor heterogeneity.  Our results show that retinoblastoma is among the least mutated cancers and signify the extreme sensitivity of the childhood retina for RB1 loss. We hypothesize that retinoblastomas arising later in retinal development benefit more from subclonal secondary alterations and therefore, these alterations are more selected for in these tumors. Targeted therapy based on these subclonal events might be insufficient for complete tumor control.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-01-26T09:08:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001691","title":"Single_Cell_RNAseq_at_various_stages_of_HiPSCs_differentiating_toward_definitive_endoderm_and_endoderm_derived_lineages_","description":"When comparing the differentiation capacities of pluripotent stem cell lines that have differentgenetic backgrounds, batch to batch experimental variablility poses a significant challenge,especially when trying to identify smaller effects. One way to address this issue is todifferentiate several different lines in the same culture dish, thereby elimating experimentalvariation. In addition, it allows researchers to analyze many more lines with less experiments.Parallel single cell RNA-Seq exploits that individual cells are tagged and hence each cell canbe reliably assigned to the donor of origin based on the genetic variants it contains. Inaddition, analyzing the genetic signature of single cells within a differentiating population canreveal differentation stages that are not easily detected in bulk RNAseq data.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"When comparing the differentiation capacities of pluripotent stem cell lines that have differentgenetic backgrounds, batch to batch experimental variablility poses a significant challenge,especially when trying to identify smaller effects. One way to address this issue is todifferentiate several different lines in the same culture dish, thereby elimating experimentalvariation. In addition, it allows researchers to many examine more lines with lessexperiments.Parallel single cell RNA-Seq exploits that individual cells are tagged and hence each cell canbe reliably assigned to the donor of origin based on the genetic variants it contains. Inaddition, analyzing the genetic signature of single cells within a differentiating population canreveal differentation stages that are not easily detected in bulk RNAseq data.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001001692","title":"ICGC PanCancer Analysis of Whole Genomes","description":"The Pancancer Analysis of Whole Genomes (PCAWG) study is an international collaboration to identify common patterns of mutation in more than 2,800 cancer whole genomes from the International Cancer Genome Consortium. Building upon previous work which examined cancer coding regions (Cancer Genome Atlas Research Network, The Cancer Genome Atlas Pan-Cancer analysis project, Nat. Genet. 2013 45:1113), this project is exploring the nature and consequences of somatic and germline variations in both coding and non-coding regions, with specific emphasis on cis-regulatory sites, non-coding RNAs, and large-scale structural alterations.","abstract":"The Pancancer Analysis of Whole Genomes (PCAWG) study is an international collaboration to identify common patterns of mutation in more than 2,800 cancer whole genomes from the International Cancer Genome Consortium. Building upon previous work which examined cancer coding regions (Cancer Genome Atlas Research Network, The Cancer Genome Atlas Pan-Cancer analysis project, Nat. Genet. 2013 45:1113), this project is exploring the nature and consequences of somatic and germline variations in both coding and non-coding regions, with specific emphasis on cis-regulatory sites, non-coding RNAs, and large-scale structural alterations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-01-29T18:16:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001693","title":"ICGC PanCancer Analysis of Whole Genomes","description":"The Pancancer Analysis of Whole Genomes (PCAWG) study is an international collaboration to identify common patterns of mutation in more than 2,800 cancer whole genomes from the International Cancer Genome Consortium. Building upon previous work which examined cancer coding regions (Cancer Genome Atlas Research Network, The Cancer Genome Atlas Pan-Cancer analysis project, Nat. Genet. 2013 45:1113), this project is exploring the nature and consequences of somatic and germline variations in both coding and non-coding regions, with specific emphasis on cis-regulatory sites, non-coding RNAs, and large-scale structural alterations.","abstract":"The Pancancer Analysis of Whole Genomes (PCAWG) study is an international collaboration to identify common patterns of mutation in more than 2,800 cancer whole genomes from the International Cancer Genome Consortium. Building upon previous work which examined cancer coding regions (Cancer Genome Atlas Research Network, The Cancer Genome Atlas Pan-Cancer analysis project, Nat. Genet. 2013 45:1113), this project is exploring the nature and consequences of somatic and germline variations in both coding and non-coding regions, with specific emphasis on cis-regulatory sites, non-coding RNAs, and large-scale structural alterations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001694","title":"Automated system for scoring hematoxylin and eosin-stained ovarian cancer sections by identifying single cells uncovered that stromal cell ratio is a significant predictor for overall survival and progression-free survival.","description":"Concerted efforts in genomic studies have revealed profound insights in prognostic ovarian cancer subtypes. On the other hand, abundant histology slides have been generated to date, yet their uses remain very limited and largely qualitative. Our goal is to develop automated histology analysis as an alternative subtyping technology for ovarian cancer that is cost-efficient and do not rely on DNA quality. We develop an automated system for scoring hematoxylin and eosin-stained (H&amp;E) primary tumour sections of 91 late-stage ovarian cancer to identify single cells including cancer and stromal cells. We demonstrated high accuracy of our system based on expert pathologists’ scores (cancer=97.1%, stromal=89.1%) as well as compared to immunohistochemistry scoring (correlation=0.87). Quantitative stromal cell ratio is significantly associated with poor overall survival after controlling for clinical parameters including debulking status and age (multivariate analysis p=0.0021, HR=2.54, CI=1.40-4.60) and progression-free survival (multivariate analysis p=0.022, HR=1.75, CI=1.09–2.82).  We demonstrate how automated image analysis enables objective quantification of microenvironmental composition of ovarian tumours. Our analysis reveals a strong effect of the tumour microenvironment on ovarian cancer progression and highlights the potential of therapeutic interventions that target the stromal compartment or cancer-stroma signalling in the stroma-high, late-stage ovarian cancer subset.","abstract":"Concerted efforts in genomic studies have revealed profound insights in prognostic ovarian cancer subtypes. On the other hand, abundant histology slides have been generated to date, yet their uses remain very limited and largely qualitative. Our goal is to develop automated histology analysis as an alternative subtyping technology for ovarian cancer that is cost-efficient and do not rely on DNA quality. We develop an automated system for scoring hematoxylin and eosin-stained (H&amp;E) primary tumour sections of 91 late-stage ovarian cancer to identify single cells including cancer and stromal cells. We demonstrated high accuracy of our system based on expert pathologists’ scores (cancer=97.1%, stromal=89.1%) as well as compared to immunohistochemistry scoring (correlation=0.87). Quantitative stromal cell ratio is significantly associated with poor overall survival after controlling for clinical parameters including debulking status and age (multivariate analysis p=0.0021, HR=2.54, CI=1.40-4.60) and progression-free survival (multivariate analysis p=0.022, HR=1.75, CI=1.09–2.82).  We demonstrate how automated image analysis enables objective quantification of microenvironmental composition of ovarian tumours. Our analysis reveals a strong effect of the tumour microenvironment on ovarian cancer progression and highlights the potential of therapeutic interventions that target the stromal compartment or cancer-stroma signalling in the stroma-high, late-stage ovarian cancer subset.","study_type":"Other","pubmed_ids":[26573438],"external_links":null,"is_released":true,"released_date":"2016-02-01T13:35:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001695","title":"Whole-exome sequencing of breast cancer metastasis and corresponding blood samples","description":"This study included samples from metastatic breast cancer patients who underwent a biopsy in the context of SAFIR01 (NCT01414933), SAFIR02 (NCT02299999), SHIVA (NCT01771458) and MOSCATO (NCT01566019) prospective trials. These French multicentre trials used high throughput genome analysis on fresh frozen tumor biopsies as a therapeutic decision tool for metastatic cancer patients, with solid cancers (SHIVA, MOSCATO) or specifically with breast cancer (SAFIR01, SAFIR02). All patients gave their informed consent for translational research and genetic analyses of their somatic DNA. Overall, whole-exome sequencing for a total of 216 pairs of metastatic tumor and unmutated DNA derived from corresponding blood samples was performed using Illumina technology.  The results of the analysis of the mutational profile of metastatic breast cancer was reported in Lefebvre et al. (PMID:28027327).","abstract":"This study included samples from metastatic breast cancer patients who underwent a biopsy in the context of SAFIR01 (NCT01414933), SAFIR02 (NCT02299999), SHIVA (NCT01771458) and MOSCATO (NCT01566019) prospective trials. These French multicentre trials used high throughput genome analysis on fresh frozen tumor biopsies as a therapeutic decision tool for metastatic cancer patients, with solid cancers (SHIVA, MOSCATO) or specifically with breast cancer (SAFIR01, SAFIR02). All patients gave their informed consent for translational research and genetic analyses of their somatic DNA. Overall, whole-exome sequencing for a total of 216 pairs of metastatic tumor and unmutated DNA derived from corresponding blood samples was performed using Illumina technology.  The results of the analysis of the mutational profile of metastatic breast cancer was reported in Lefebvre et al. (PMID:28027327).","study_type":"Other","pubmed_ids":[28027327],"external_links":null,"is_released":true,"released_date":"2016-02-02T12:54:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001696","title":"Combination_Therapies_for_Personalised_Cancer_Medicine_in_HCC827","description":"This study involves mutagenizing HCC827 with ENU to identify those mutations which engender resistance to targeted treatment.","abstract":"In the last decade we have begun to move towards the use of targeted therapeutics in the clinic, often resulting in dramatic response rates in cancer patients. However, clinical experience has demonstrated time and time again that such responses are invariably followed by the development of drug resistance. Identification of the underlying mechanisms may enable us to reverse such resistance. Traditional methods of modelling this resistance in vitro can lead to a plethora of potential resistance mechanisms that can be difficult to decipher.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001697","title":"Melanoma_C32_ENU_Resistance_to_Single_Agent_Therapy","description":"This study involves mutagenizing C32, a melanoma cell line, with ENU to identify those mutations which engender resistance to a targeted treatment.","abstract":"In the last decade we have begun to move towards the use of targeted therapeutics in the clinic, often resulting in dramatic response rates in cancer patients. However, clinical experience has demonstrated time and time again that such responses are invariably followed by the development of drug resistance. Identification of the underlying mechanisms may enable us to reverse such resistance. Traditional methods of modelling this resistance in vitro can lead to a plethora of potential resistance mechanisms that can be difficult to decipher.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-03T12:49:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001698","title":"Warm_Autopsy_Single_Cell_X10","description":"Study of cell lineage and embryogenesis using biopsy samples from sites across the whole body (post mortem). Sample donors are recruited sensitively through the Phoenix study and consent to samples being taken after their death for both the Phoenix study and this WTSI study.","abstract":"Study of cell lineage and embryogenesis using biopsy samples from sites across the whole body (post mortem). Sample donors are recruited sensitively through the Phoenix study and consent to samples being taken after their death for both the Phoenix study and this WTSI study.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-03T12:58:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001699","title":"Genetic sequencing of MODY patients.","description":"Maturity-onset Diabetes of the young (MODY) is an early-onset, autosomal dominant form of non-insulin dependent diabetes. Genetic diagnosis of MODY can transform patient management. Earlier data on the genetic predisposition to MODY have come primarily from familial studies in populations of European origin. Using next generation sequencing, we carried out a comprehensive genomic analysis of 289 individuals from India that included 152 clinically diagnosed MODY cases to identify variants in known MODY genes. Our findings report that HNF1A and ABCC8 are among the most frequently mutated MODY genes in south India.","abstract":"Maturity-onset Diabetes of the young (MODY) is an early-onset, autosomal dominant form of non-insulin dependent diabetes. Genetic diagnosis of MODY can transform patient management. Earlier data on the genetic predisposition to MODY have come primarily from familial studies in populations of European origin. Using next generation sequencing, we carried out a comprehensive genomic analysis of 289 individuals from India that included 152 clinically diagnosed MODY cases to identify variants in known MODY genes. Our findings report that HNF1A and ABCC8 are among the most frequently mutated MODY genes in south India.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-03T22:04:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001700","title":"Post-zygotic germline mutations in sperm","description":"These data from sperm were generated to demonstrate detection of post-zygotic mutations in the male germline. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"These data from sperm were generated to demonstrate detection of post-zygotic mutations in the male germline. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-04T16:21:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001701","title":"Very short reads file for testing purposes","description":"Very short FASTQ reads file for testing purposes","abstract":"Very short FASTQ reads file for testing purposes","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-05T09:26:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001702","title":"Patient-derived conditionally reprogrammed cells (CRCs) were established and characterized to assess their biological properties and to apply these to test the efficacies of drugs.","description":"RNA seq data was used for the characterization and profiling of the created patient-derived cells and in vivo tissue.","abstract":"RNA seq data was used for the characterization and profiling of the created patient-derived cells and in vivo tissue.","study_type":"Other","pubmed_ids":[27160946],"external_links":null,"is_released":true,"released_date":"2016-02-06T09:40:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001703","title":"Targeted NGS of circulating tumor DNA","description":"Targeted NGS of circulating tumor DNA","abstract":"Targeted NGS of circulating tumor DNA","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001704","title":"LifeLines-DEEP population multi-omix cohort from the noth of the Netherlands.","description":"The LifeLines-DEEP cohort is a sub-cohort of the LifeLines cohort (167,729 participants) that employs a broad range of investigative procedures to assess the biomedical, socio-demographic, behavioral, physical and psychological factors that contribute to health and disease in the general Dutch population, (Scholtens 2015). A subset of approximately 1,500 participants also took part in LifeLines-DEEP. For these participants, additional biological materials were collected, including analysis of the gut microbiome composition. The phenotyping and processing of LifeLines-DEEP has been described in Tigchelaar (2015).","abstract":"The LifeLines-DEEP cohort is a sub-cohort of the LifeLines cohort (167,729 participants) that employs a broad range of investigative procedures to assess the biomedical, socio-demographic, behavioral, physical and psychological factors that contribute to health and disease in the general Dutch population, (Scholtens 2015). A subset of approximately 1,500 participants also took part in LifeLines-DEEP. For these participants, additional biological materials were collected, including analysis of the gut microbiome composition. The phenotyping and processing of LifeLines-DEEP has been described in Tigchelaar (2015).","study_type":"Other","pubmed_ids":[5502107,26319774],"external_links":null,"is_released":true,"released_date":"2016-02-08T09:16:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001705","title":"CTTV_macrophage_screen","description":"Macrophages are myeloid cells that perform crucial functions in innate immunity, and dysregulation of macrophage cellular function is implicated in a wide variety of disorders including asthma, atherosclerosis, chronic obstructive pulmonary disease, cancer, neurodegeneration, fibrosis, arthritis and inflammatory bowel disorders. Development of therapeutic targets that alter key human macrophage cellular functions relies on a systematic approach for identifying genes that regulate the major macrophage cellular functions: proliferation, motility, phagocytosis and secretion. However, performing robust genetic screens is impossible in primary human macrophages due to their limited proliferative capacity and the small quantity of material available from any one donor. The goal of this project is to develop a robust genetic screening platform in human macrophages. In collaboration with the Pathogens group at WTSI, we have developed an experimental pipeline for generation of human macrophages that closely resemble their primary counterparts and recapitulate key cellular functions from induced pluripotent stem cells (hIPSCs). We will use recently developed lentiviral CRISPR-guide RNA llibraries to perform genetic screens for key macrophage cellular phenotypes. As an initial exemplar assay we will perform a genetic screen for phagocytosis using fluorescein isothiocyanate (FITC)-labeled zymosan particles. The cellular assay for phagocytosis is robust and there are already some well-characterised positive controls (ELMO1, GULP1). However, we anticipate that this platform can extend to any cell phenotype on which cells can be sorted,  synergising with ongoing CTTV initiatives in IBD and airway diseases, as well as with GSK interests in COPD. Initially, we will perform a direct comparison of cellular assay performance in primary blood monocyte-derived macrophages and IPS-derived macrophages. Primary macrophages will be derived from volunteers from the Cambridge BioResource that have also donated to the Human Induced Pluripotent Stem Cells Initiative (HIPSCI). We will compare the transcriptomes of the IPS and blood derived macrophages in the cellular assay, for example before and after exposure to zymosan particles, using RNA-seq across a minimum of three biological replicates to identify any possible differences in response between the IPS-derived and the primary macrophages.  Following the pilot comparison, we will engineer an IPS line to endogenously express Cas9. We will comprehensively characterise the impact of endogenous Cas9 expression on the cells using RNA-seq and ATAC-seq. If significant impacts of Cas9 expression are indicated, we will modify the endogenous Cas9 to express with an inducible promoter. The engineered line will then be differentiated into embryoid bodies and subsequently into macrophages, a process taking 2-3 weeks. Following differentiation, macrophage precursors can be harvested weekly for up to 9 months, providing a continuous source of cellular material with cell numbers of the order of 10M per week easily achievable. Following differentiation, the cell population will be transduced with a genome-wide lentiviral library. Preliminary data suggests that transduction efficiencies of a lentiviral library in IPS-derived macrophages are between 10 and 20%, which is sufficient for complete genome coverage. Following transduction, a cellular assay will be performed to screen cells for a specific phenotype. For example, cells treated with FITC-labeled zymosan, fluoresce upon engulfment of the particle. Fluorescing cells will be flow sorted and guide RNAs (gRNAs) from the fluorescent and non fluorescent populations will be deep sequenced. We will compare gRNA frequency between the two populations to identify gRNAs that are at significantly higher frequency in the non-fluorescent population, indicating that the mutants inactivate genes that are necessary for phagocytosis. We will perform 5-10 replicate screens for each phenotype, and specific targets will be independently validated in both IPS and primary cells by mutating specific genes detected in the screen in a clonal population and their assay performance with the wild type line. Following development of the screening pipeline, we will extend screens to other macrophage cell phenotypes of interest, with input from GSK DPUs. Possible extensions could include macrophage proliferation, bacterial phagocytosis, autophagy or bacterial killing. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Macrophages are myeloid cells that perform crucial functions in innate immunity, and dysregulation of macrophage cellular function is implicated in a wide variety of disorders including asthma, atherosclerosis, chronic obstructive pulmonary disease, cancer, neurodegeneration, fibrosis, arthritis and inflammatory bowel disorders. Development of therapeutic targets that alter key human macrophage cellular functions relies on a systematic approach for identifying genes that regulate the major macrophage cellular functions: proliferation, motility, phagocytosis and secretion. However, performing robust genetic screens is impossible in primary human macrophages due to their limited proliferative capacity and the small quantity of material available from any one donor. The goal of this project is to develop a robust genetic screening platform in human macrophages. In collaboration with the Pathogens group at WTSI, we have developed an experimental pipeline for generation of human macrophages that closely resemble their primary counterparts and recapitulate key cellular functions from induced pluripotent stem cells (hIPSCs). We will use recently developed lentiviral CRISPR-guide RNA llibraries to perform genetic screens for key macrophage cellular phenotypes. As an initial exemplar assay we will perform a genetic screen for phagocytosis using fluorescein isothiocyanate (FITC)-labeled zymosan particles. The cellular assay for phagocytosis is robust and there are already some well-characterised positive controls (ELMO1, GULP1). However, we anticipate that this platform can extend to any cell phenotype on which cells can be sorted,  synergising with ongoing CTTV initiatives in IBD and airway diseases, as well as with GSK interests in COPD. Initially, we will perform a direct comparison of cellular assay performance in primary blood monocyte-derived macrophages and IPS-derived macrophages. Primary macrophages will be derived from volunteers from the Cambridge BioResource that have also donated to the Human Induced Pluripotent Stem Cells Initiative (HIPSCI). We will compare the transcriptomes of the IPS and blood derived macrophages in the cellular assay, for example before and after exposure to zymosan particles, using RNA-seq across a minimum of three biological replicates to identify any possible differences in response between the IPS-derived and the primary macrophages.  Following the pilot comparison, we will engineer an IPS line to endogenously express Cas9. We will comprehensively characterise the impact of endogenous Cas9 expression on the cells using RNA-seq and ATAC-seq. If significant impacts of Cas9 expression are indicated, we will modify the endogenous Cas9 to express with an inducible promoter. The engineered line will then be differentiated into embryoid bodies and subsequently into macrophages, a process taking 2-3 weeks. Following differentiation, macrophage precursors can be harvested weekly for up to 9 months, providing a continuous source of cellular material with cell numbers of the order of 10M per week easily achievable. Following differentiation, the cell population will be transduced with a genome-wide lentiviral library. Preliminary data suggests that transduction efficiencies of a lentiviral library in IPS-derived macrophages are between 10 and 20%, which is sufficient for complete genome coverage. Following transduction, a cellular assay will be performed to screen cells for a specific phenotype. For example, cells treated with FITC-labeled zymosan, fluoresce upon engulfment of the particle. Fluorescing cells will be flow sorted and guide RNAs (gRNAs) from the fluorescent and non fluorescent populations will be deep sequenced. We will compare gRNA frequency between the two populations to identify gRNAs that are at significantly higher frequency in the non-fluorescent population, indicating that the mutants inactivate genes that are necessary for phagocytosis. We will perform 5-10 replicate screens for each phenotype, and specific targets will be independently validated in both IPS and primary cells by mutating specific genes detected in the screen in a clonal population and their assay performance with the wild type line. Following development of the screening pipeline, we will extend screens to other macrophage cell phenotypes of interest, with input from GSK DPUs. Possible extensions could include macrophage proliferation, bacterial phagocytosis, autophagy or bacterial killing.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001706","title":"Identification of gene mutations and fusion genes in patients with Sézary Syndrome","description":"Sezary syndrome (SS) is a leukemic form of cutaneous T-cell lymphoma (CTCL) with an aggressive clinical course. The goal of our study is to understand the genetic basis of the disease by looking for driver gene mutations and fusion genes in 15 erythrodermic patients with circulating Sezary cels, fourteen of them fulfilling the diagnostic criteria of SS. Peripheral blood samples were collected for each patient and CD4+ T-lymphocytes and Granulocytes were isolated. DNA and RNA was extracted for matched normal and tumor materials. Whole exome sequencing was performed on matched normal and tumor tissues of 12 patients and RNA sequencing was performed on 10 patients. For 7 of these patients, we have both exome as well as RNA sequencing data. In this study, we present a complex genomic landscape of Sezary syndrome with several point mutations, copy number variations and fusion events which could contribute to the pathogenesis of SS.","abstract":"Sezary syndrome (SS) is a leukemic form of cutaneous T-cell lymphoma (CTCL) with an aggressive clinical course. The goal of our study is to understand the genetic basis of the disease by looking for driver gene mutations and fusion genes in 15 erythrodermic patients with circulating Sezary cels, fourteen of them fulfilling the diagnostic criteria of SS. Peripheral blood samples were collected for each patient and CD4+ T-lymphocytes and Granulocytes were isolated. DNA and RNA was extracted for matched normal and tumor materials. Whole exome sequencing was performed on matched normal and tumor tissues of 12 patients and RNA sequencing was performed on 10 patients. For 7 of these patients, we have both exome as well as RNA sequencing data. In this study, we present a complex genomic landscape of Sezary syndrome with several point mutations, copy number variations and fusion events which could contribute to the pathogenesis of SS.","study_type":"Other","pubmed_ids":[27039262],"external_links":null,"is_released":true,"released_date":"2016-02-08T15:00:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001707","title":"PanCancer Analysis of Whole Genomes (Dummy)","description":"The Pancancer Analysis of Whole Genomes (PCAWG) study is an international collaboration to identify common patterns of mutation in more than 2,800 cancer whole genomes from the International Cancer Genome Consortium. Building upon previous work which examined cancer coding regions (Cancer Genome Atlas Research Network, The Cancer Genome Atlas Pan-Cancer analysis project, Nat. Genet. 2013 45:1113), this project is exploring the nature and consequences of somatic and germline variations in both coding and non-coding regions, with specific emphasis on cis-regulatory sites, non-coding RNAs, and large-scale structural alterations.","abstract":"The Pancancer Analysis of Whole Genomes (PCAWG) study is an international collaboration to identify common patterns of mutation in more than 2,800 cancer whole genomes from the International Cancer Genome Consortium. Building upon previous work which examined cancer coding regions (Cancer Genome Atlas Research Network, The Cancer Genome Atlas Pan-Cancer analysis project, Nat. Genet. 2013 45:1113), this project is exploring the nature and consequences of somatic and germline variations in both coding and non-coding regions, with specific emphasis on cis-regulatory sites, non-coding RNAs, and large-scale structural alterations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001708","title":"RNA_seq_of_Toxoplasma_gondii_response_in_human_macrophages","description":"Toxoplasmosis is a zoonotic disease caused by a ubiquitous protozoan parasite called Toxoplasma gondii, which caninfect all mammal and bird species throughout the world. seroprevalence varies widely between countries. Studieshave estimated that between 7-34% of people in the UK have been infected with T. gondii. The vast majority of thesepeople will not have noticed any symptoms, however about 10% of people develop a mild to moderate self limitingflu-like illness. Following the acute active stage of the infection the parasite persists in the body in the form of cysts,particularly in heart and skeletal muscle and nervous system tissues, for many years, and usually for life. Inimmunocompetent persons these cysts do not pose a health risk. We will use RNA-seq to quantify the transcriptionalresponse of macrophages to T gondii infection.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Toxoplasmosis is a zoonotic disease caused by a ubiquitous protozoan parasite called Toxoplasma gondii, which caninfect all mammal and bird species throughout the world. seroprevalence varies widely between countries. Studieshave estimated that between 7-34% of people in the UK have been infected with T. gondii. The vast majority of thesepeople will not have noticed any symptoms, however about 10% of people develop a mild to moderate self limitingflu-like illness. Following the acute active stage of the infection the parasite persists in the body in the form of cysts,particularly in heart and skeletal muscle and nervous system tissues, for many years, and usually for life. Inimmunocompetent persons these cysts do not pose a health risk. We will use RNA-seq to quantify the transcriptionalresponse of macrophages to T gondii infection.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-10T10:42:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001709","title":"Histological Transformation and Progression in Follicular Lymphoma: a Clonal Evolution Study","description":"Background: Follicular lymphoma (FL) is an indolent, yet incurable B-cell malignancy. A subset of patients experience increased mortality rate driven by two distinct clinical end points: histological transformation and early progression after immuno-chemotherapy. The nature of tumor clonal dynamics leading to these clinical endpoints is poorly understood and previously determined genetic alterations do not explain the majority of transformed cases or accurately predict early progressive disease. We contend that detailed knowledge of the expansion patterns of specific cell populations plus their associated mutations would provide insight into therapeutic strategies and disease biology over the timecourse of FL clinical histories.\n\nMethods and Findings: Using a combination of whole genome sequencing, targeted deep sequencing and digital droplet PCR on matched diagnostic and relapse specimens, we deciphered the constituent clonal populations in n=15 transformation patients and n=6 progressors, and measured their change in abundance over time. We observed widely divergent patterns of clonal dynamics in transformed cases relative to progressed cases. Transformation specimens were generally composed of clones that were rare or absent in diagnostic specimens, consistent with dramatic clonal expansions that came to dominate the transformation specimen. This pattern was independent of time to transformation and treatment modality. By contrast, progression specimens were composed of clones that were already present in the diagnostic specimens and exhibited only moderate clonal dynamics, even in the presence of immuno-chemotherapy. Analysis of somatic mutations impacting 94 genes was undertaken in a validation cohort consisting of 395 samples from 277 patients in order to decipher disrupted biology in the two clinical endpoints. We found 12 genes were more commonly mutated in transformed samples than in preceding FL, including TP53, B2M, CCND3, GNA13, S1PR2 and P2RY8. Moreover, 10 genes were more commonly mutated in diagnostic specimens of early progressors including TP53, BTG1, MKI67 and XBP1.\n\nConclusions: Our results illuminate contrasting modes of evolution shaping the clinical histories of transformation and progression. They have implication for interpretation of evolutionary dynamics in the context of treatment-induced selective pressures, and indicate that transformation and progression will require different clinical management strategies.","abstract":"Background: Follicular lymphoma (FL) is an indolent, yet incurable B-cell malignancy. A subset of patients experience increased mortality rate driven by two distinct clinical end points: histological transformation and early progression after immuno-chemotherapy. The nature of tumor clonal dynamics leading to these clinical endpoints is poorly understood and previously determined genetic alterations do not explain the majority of transformed cases or accurately predict early progressive disease. We contend that detailed knowledge of the expansion patterns of specific cell populations plus their associated mutations would provide insight into therapeutic strategies and disease biology over the timecourse of FL clinical histories.\n\nMethods and Findings: Using a combination of whole genome sequencing, targeted deep sequencing and digital droplet PCR on matched diagnostic and relapse specimens, we deciphered the constituent clonal populations in n=15 transformation patients and n=6 progressors, and measured their change in abundance over time. We observed widely divergent patterns of clonal dynamics in transformed cases relative to progressed cases. Transformation specimens were generally composed of clones that were rare or absent in diagnostic specimens, consistent with dramatic clonal expansions that came to dominate the transformation specimen. This pattern was independent of time to transformation and treatment modality. By contrast, progression specimens were composed of clones that were already present in the diagnostic specimens and exhibited only moderate clonal dynamics, even in the presence of immuno-chemotherapy. Analysis of somatic mutations impacting 94 genes was undertaken in a validation cohort consisting of 395 samples from 277 patients in order to decipher disrupted biology in the two clinical endpoints. We found 12 genes were more commonly mutated in transformed samples than in preceding FL, including TP53, B2M, CCND3, GNA13, S1PR2 and P2RY8. Moreover, 10 genes were more commonly mutated in diagnostic specimens of early progressors including TP53, BTG1, MKI67 and XBP1.\n\nConclusions: Our results illuminate contrasting modes of evolution shaping the clinical histories of transformation and progression. They have implication for interpretation of evolutionary dynamics in the context of treatment-induced selective pressures, and indicate that transformation and progression will require different clinical management strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-10T17:03:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001710","title":"The Haplotype Reference Consortium","description":"The Haplotype Reference Consortium (HRC) will create a large reference panel of human haplotypes by combining together sequencing data from multiple cohorts. By combining together multiple cohorts, the reference panels produced by the project will be as large as possible in terms of both number of haplotypes, and numbers of variants. This will increase the accuracy of the genotype imputation, especially at low-frequency variants, and the number of imputable variants, thus increasing the power of GWAS.","abstract":"The Haplotype Reference Consortium (HRC) will create a large reference panel of human haplotypes by combining together sequencing data from multiple cohorts. By combining together multiple cohorts, the reference panels produced by the project will be as large as possible in terms of both number of haplotypes, and numbers of variants. This will increase the accuracy of the genotype imputation, especially at low-frequency variants, and the number of imputable variants, thus increasing the power of GWAS.","study_type":"Other","pubmed_ids":[27548312],"external_links":null,"is_released":true,"released_date":"2016-02-10T20:42:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001711","title":"Korean Young Age Diffuse Gastric Cancers","description":"The incidence of diffuse gastric cancers (DGC) remains steadily high, but relatively small numbers of DGCs have been evaluated with whole exome sequencing (WES). Clinicopathological features of DGC vary according to age, but the molecular basis for these variations is unclear. To identify genomic alteration in this unique subset of gastric cancers, whole exome and SNP6 analyses were performed using frozen cancer tissue. The same analyses were also performed using blood of the same patients.","abstract":"The incidence of diffuse gastric cancers (DGC) remains steadily high, but relatively small numbers of DGCs have been evaluated with whole exome sequencing (WES). Clinicopathological features of DGC vary according to age, but the molecular basis for these variations is unclear. To identify genomic alteration in this unique subset of gastric cancers, whole exome and SNP6 analyses were performed using frozen cancer tissue. The same analyses were also performed using blood of the same patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-11T08:07:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001712","title":"Tumor-Associated Macrophages as a Key switch in the Acquisition of Mesenchymal Traits of Glioblastoma","description":"Mesenchymal (MES) differentiation in glioblastoma (GBM) plays critical roles in enhancing clinical aggressiveness. Recent studies suggested significant enrichment of tumor-associated macrophages (TAMs) in MES GBMs carrying dismal prognosis, yet the integral roles of TAMs in mediating acquisition of MES features remains unknown. Transcriptome analysis of 55 longitudinal GBM pairs revealed meaningful associations between MES subtype upon relapse accompanying increased TAM recruitment and worse prognosis. A shift towards MES state and enhanced tumor aggressiveness of non-MES GBM stem-like cells by MES GBM-associated TAMs (MES-TAMs) were confirmed pre- clinically. Furthermore, comparison of transcriptome profiling of TAMs, isolated directly from patient tumors, identified MES-origin TAM signature. Prognostic significance and a strong association with a MES phenotype of this signature in newly diagnosed cases in TCGA and matched pairs of GBM highlight the pivotal contribution of TAM-derived signals to triggering the MES transition in GBM progression.","abstract":"Mesenchymal (MES) differentiation in glioblastoma (GBM) plays critical roles in enhancing clinical aggressiveness. Recent studies suggested significant enrichment of tumor-associated macrophages (TAMs) in MES GBMs carrying dismal prognosis, yet the integral roles of TAMs in mediating acquisition of MES features remains unknown. Transcriptome analysis of 55 longitudinal GBM pairs revealed meaningful associations between MES subtype upon relapse accompanying increased TAM recruitment and worse prognosis. A shift towards MES state and enhanced tumor aggressiveness of non-MES GBM stem-like cells by MES GBM-associated TAMs (MES-TAMs) were confirmed pre- clinically. Furthermore, comparison of transcriptome profiling of TAMs, isolated directly from patient tumors, identified MES-origin TAM signature. Prognostic significance and a strong association with a MES phenotype of this signature in newly diagnosed cases in TCGA and matched pairs of GBM highlight the pivotal contribution of TAM-derived signals to triggering the MES transition in GBM progression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001713","title":"PAGE: Prenatal Assessment of Genomes and Exomes","description":"The Prenatal Assessment of Genomes and Exomes (PAGE) study is a multicentre prospective trial, performing exome sequence analysis on samples from 1000 families with structural anomalies in prenatal ultrasound screening but normal aneuploidy results.  The data will enable discovery of novel genetic disorders and increase the diagnostic yield.  Where appropriate, results will be reported back to the families at the end of the pregnancy, after thorough clinical review.  Ultimately, the translation of the acquired know-how into cost-effective prenatal diagnostic sequencing will improve genetics-derived prognoses and allow more informed parental counselling as well as management of pregnancy and childbirth.","abstract":"The Prenatal Assessment of Genomes and Exomes (PAGE) study is a multicentre prospective trial, performing exome sequence analysis on samples from 1000 families with structural anomalies in prenatal ultrasound screening but normal aneuploidy results.  The data will enable discovery of novel genetic disorders and increase the diagnostic yield.  Where appropriate, results will be reported back to the families at the end of the pregnancy, after thorough clinical review.  Ultimately, the translation of the acquired know-how into cost-effective prenatal diagnostic sequencing will improve genetics-derived prognoses and allow more informed parental counselling as well as management of pregnancy and childbirth.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-11T11:58:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001714","title":"WES analysis of a mixed cohort of pituitary tumors","description":"BACKGROUND:  Sporadic pituitary adenomas are the second most common primary brain tumor, but their genetics remains incompletely understood. We performed deep DNA sequencing of 42 pituitary macroadenomas, including hormonally active and atypical adenomas.   METHODS:  Pituitary adenomas representative of a spectrum of histopathologic subtypes, primary and recurrent tumors, and MIB-1 proliferative indices were profiled. Whole-exome sequencing was performed on tumors and paired blood followed by analysis of somatic copy number alteration and mutation.   RESULTS:  On the whole, the tumors harbored a low rate of mutations, similar to other benign brain tumors. However, almost one-third (29%) exhibited somatic copy-number alterations across large fractions of the genome (up to 99%). Despite such widespread genomic disruption, these tumors had few focal events, which is atypical among highly-disrupted cancers. The other 71% of tumors formed a distinct molecular class, with somatic copy-number alterations involving less than 6% of the genome. Among the highly-disrupted group, 92% were functional or atypical null-cell adenomas, whereas 87% of the less-disrupted group were clinically non-functional adenomas. The only significantly recurrent events were arm-level losses of chromosomes 1, 2, 11, and 18. No significantly recurrent mutations or insertion/deletion events were identified, suggesting no genes are altered by exomic mutations in &gt;15% of pituitary tumors.  CONCLUSIONS:  Genomic characterization of a large series of sporadic pituitary adenomas reveals two classes of tumor, based on genomic disruption from arm-level copy-number alterations, which associate with hormonal and histologic subtypes.","abstract":"BACKGROUND:  Sporadic pituitary adenomas are the second most common primary brain tumor, but their genetics remains incompletely understood. We performed deep DNA sequencing of 42 pituitary macroadenomas, including hormonally active and atypical adenomas.   METHODS:  Pituitary adenomas representative of a spectrum of histopathologic subtypes, primary and recurrent tumors, and MIB-1 proliferative indices were profiled. Whole-exome sequencing was performed on tumors and paired blood followed by analysis of somatic copy number alteration and mutation.   RESULTS:  On the whole, the tumors harbored a low rate of mutations, similar to other benign brain tumors. However, almost one-third (29%) exhibited somatic copy-number alterations across large fractions of the genome (up to 99%). Despite such widespread genomic disruption, these tumors had few focal events, which is atypical among highly-disrupted cancers. The other 71% of tumors formed a distinct molecular class, with somatic copy-number alterations involving less than 6% of the genome. Among the highly-disrupted group, 92% were functional or atypical null-cell adenomas, whereas 87% of the less-disrupted group were clinically non-functional adenomas. The only significantly recurrent events were arm-level losses of chromosomes 1, 2, 11, and 18. No significantly recurrent mutations or insertion/deletion events were identified, suggesting no genes are altered by exomic mutations in &gt;15% of pituitary tumors.  CONCLUSIONS:  Genomic characterization of a large series of sporadic pituitary adenomas reveals two classes of tumor, based on genomic disruption from arm-level copy-number alterations, which associate with hormonal and histologic subtypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-11T19:16:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001715","title":"Copy number profiling of primary samples and cell lines of retinoblastoma","description":"While RB1 loss initiates retinoblastoma development, additional somatic copy number alterations (SCNAs) can drive tumor progression. Although SCNAs have been identified with good concordance between studies at a cytoband resolution, accurate identification of single genes for all recurrent SCNAs is still challenging. This study presents a comprehensive meta-analysis of genome-wide SCNAs integrated with gene expression profiling data, narrowing down the list of plausible retinoblastoma driver genes. We performed SCNA profiling of 45 primary retinoblastoma samples and 8 retinoblastoma cell lines by high-resolution microarrays. We combined our data with genomic, clinical and histopathological data of ten published genome-wide SCNA studies, which strongly enhanced the power of our analyses (N=310). Comprehensive recurrence analysis of SCNAs in all studies integrated with gene expression data allowed us to reduce candidate gene lists for 1q, 2p, 6p, 7q and 13q to a limited gene set. Besides the well-established driver genes RB1 (13q-loss) and MYCN (2p-gain) we identified CRB1 and NEK7 (1q-gain), SOX4 (6p-gain) and NUP205 (7q-gain) as novel retinoblastoma driver candidates. Depending on the sample subset and algorithms used, alternative candidates were identified including MIR181 (1q-gain) and DEK (6p gain). Remarkably, our study showed that copy number gains rarely exceeded change of one copy, even in pure tumor samples with 100% homozygosity at the RB1 locus (N=34), which is indicative for intra-tumor heterogeneity. In addition, profound between-tumor variability was observed that was associated with age at diagnosis and differentiation grades. Since focal alterations at commonly altered chromosome regions were rare except for 2p24.3 (MYCN), further functional validation of the oncogenic potential of the described candidate genes is now required. For further investigations, our study provides a refined and revised set of candidate retinoblastoma driver genes.","abstract":"While RB1 loss initiates retinoblastoma development, additional somatic copy number alterations (SCNAs) can drive tumor progression. Although SCNAs have been identified with good concordance between studies at a cytoband resolution, accurate identification of single genes for all recurrent SCNAs is still challenging. This study presents a comprehensive meta-analysis of genome-wide SCNAs integrated with gene expression profiling data, narrowing down the list of plausible retinoblastoma driver genes. We performed SCNA profiling of 45 primary retinoblastoma samples and 8 retinoblastoma cell lines by high-resolution microarrays. We combined our data with genomic, clinical and histopathological data of ten published genome-wide SCNA studies, which strongly enhanced the power of our analyses (N=310). Comprehensive recurrence analysis of SCNAs in all studies integrated with gene expression data allowed us to reduce candidate gene lists for 1q, 2p, 6p, 7q and 13q to a limited gene set. Besides the well-established driver genes RB1 (13q-loss) and MYCN (2p-gain) we identified CRB1 and NEK7 (1q-gain), SOX4 (6p-gain) and NUP205 (7q-gain) as novel retinoblastoma driver candidates. Depending on the sample subset and algorithms used, alternative candidates were identified including MIR181 (1q-gain) and DEK (6p gain). Remarkably, our study showed that copy number gains rarely exceeded change of one copy, even in pure tumor samples with 100% homozygosity at the RB1 locus (N=34), which is indicative for intra-tumor heterogeneity. In addition, profound between-tumor variability was observed that was associated with age at diagnosis and differentiation grades. Since focal alterations at commonly altered chromosome regions were rare except for 2p24.3 (MYCN), further functional validation of the oncogenic potential of the described candidate genes is now required. For further investigations, our study provides a refined and revised set of candidate retinoblastoma driver genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-12T09:06:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001716","title":"Genome_Diversity_in_Africa_Project__Ethiopia","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region.The Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformaticsThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001717","title":"Genome_Diversity_in_Africa_Project__Egypt","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region.The Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformaticsThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001718","title":"Genome_Diversity_in_Africa_Project__Khoe_San","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region.The Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformaticsThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001719","title":"Genome_Diversity_in_Africa_Project__Chad","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region.The Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformaticsThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001720","title":"Multi-region ultra-deep sequencing reveals early inter-mixing and variable levels of intratumoral heterogeneity in colorectal cancer","description":"Background: Intratumor heterogeneity (ITH) contributes to cancer progression and chemoresistance. We sought to comprehensively describe ITH of somatic mutations, copy number and transcriptomic alterations involving clinically and biologically relevant genes pathways in colorectal cancer (CRC). \nMethods: We performed multi-region, high-depth (384x on average) sequencing of 799 cancer-associated genes in 24 spatially separated primary tumor and non-malignant tissues from 4 treatment-naïve CRC patients. We then used ultra-deep sequencing (17,075x on average) to accurately verify presence or absence of identified somatic mutations in each sector. We also digitally measured gene expression and copy number alterations using NanoString assays. We identified subclonal point mutations and determined the mutational timing and phylogenetic relationships among spatially separated sectors of each tumor.\nResults: Truncal mutations, those shared by all sectors in the tumor, affected well described driver genes such as APC, TP53, and KRAS. With sequencing at 17,075x, we found that mutations first detected at a sequencing depth of 384x were in fact more widely shared among sectors than originally assessed. Interestingly, ultra-deep sequencing also revealed some mutations that were present in all spatially dispersed sectors, but at subclonal levels. \nConclusions: Ultra-high depth validation sequencing, copy number analysis, and gene expression profiling provided a comprehensive and accurate genomic landscape of spatial heterogeneity in CRC. Ultra-deep sequencing allowed more sensitive detection of somatic mutations and a more accurate assessment of ITH. By detecting subclonal mutations with ultra-deep sequencing, we traced the genomic histories of each tumor and relative timing of mutational events. We found evidence of early mixing, in which subclonal ancestral mutations inter-mixed across sectors before the acquisition of subsequent non-truncal mutations. Our findings also indicate that different CRC patients display markedly variable ITH, suggesting that each patient’s tumor possess a unique genomic history and spatial organization.","abstract":"Background: Intratumor heterogeneity (ITH) contributes to cancer progression and chemoresistance. We sought to comprehensively describe ITH of somatic mutations, copy number and transcriptomic alterations involving clinically and biologically relevant genes pathways in colorectal cancer (CRC). \nMethods: We performed multi-region, high-depth (384x on average) sequencing of 799 cancer-associated genes in 24 spatially separated primary tumor and non-malignant tissues from 4 treatment-naïve CRC patients. We then used ultra-deep sequencing (17,075x on average) to accurately verify presence or absence of identified somatic mutations in each sector. We also digitally measured gene expression and copy number alterations using NanoString assays. We identified subclonal point mutations and determined the mutational timing and phylogenetic relationships among spatially separated sectors of each tumor.\nResults: Truncal mutations, those shared by all sectors in the tumor, affected well described driver genes such as APC, TP53, and KRAS. With sequencing at 17,075x, we found that mutations first detected at a sequencing depth of 384x were in fact more widely shared among sectors than originally assessed. Interestingly, ultra-deep sequencing also revealed some mutations that were present in all spatially dispersed sectors, but at subclonal levels. \nConclusions: Ultra-high depth validation sequencing, copy number analysis, and gene expression profiling provided a comprehensive and accurate genomic landscape of spatial heterogeneity in CRC. Ultra-deep sequencing allowed more sensitive detection of somatic mutations and a more accurate assessment of ITH. By detecting subclonal mutations with ultra-deep sequencing, we traced the genomic histories of each tumor and relative timing of mutational events. We found evidence of early mixing, in which subclonal ancestral mutations inter-mixed across sectors before the acquisition of subsequent non-truncal mutations. Our findings also indicate that different CRC patients display markedly variable ITH, suggesting that each patient’s tumor possess a unique genomic history and spatial organization.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001721","title":"Statin_induced_expression_differences_in_iPSC_derived_hepatocyte_like_cells__RNAseq_","description":"Statins are used World-wide to lower blood cholesterol levels by inhibition of Hydroxymethylglutaryl CoA Reductase in the liver. Statins have pleiotropic effects and this pilot project, using human iPSC derived hepatocyte-like cells, will study differences in gene expression before and after exposing the cells to simvastatin at various doses.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Statins are used World-wide to lower blood cholesterol levels by inhibition of Hydroxymethylglutaryl CoA Reductase in the liver. Statins have pleiotropic effects and this pilot project, using human iPSC derived hepatocyte-like cells, will study differences in gene expression before and after exposing the cells to simvastatin at various doses.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001722","title":"PanCancer Analysis of Whole Genomes - edit","description":null,"abstract":"The Pancancer Analysis of Whole Genomes (PCAWG) study is an international collaboration to identify common patterns of mutation in more than 2,800 cancer whole genomes from the International Cancer Genome Consortium. Building upon previous work which examined cancer coding regions (Cancer Genome Atlas Research Network, The Cancer Genome Atlas Pan-Cancer analysis project, Nat. Genet. 2013 45:1113), this project is exploring the nature and consequences of somatic and germline variations in both coding and non-coding regions, with specific emphasis on cis-regulatory sites, non-coding RNAs, and large-scale structural alterations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001723","title":"Genomic characterization of esophageal squamous cell carcinoma reveals critical genes underlying tumorigenesis and poor prognosis","description":"The genetic mechanisms underlying the poor prognosis of esophageal squamous cell carcinoma (ESCC) are not well understood. In this study, we comprehensively characterized somatic mutations, copy number alterations (SCNAs)/structural variants (SVs) found in ESCC from sequencing 10 whole-genome and 57 whole-exome matched tumor-normal pairs. We identified multiple somatic mutations seen previously in known cancer pathways and identified candidate genes for ESCC including VANGL1 and MIR4707. A survival analysis based on the expression profiles of 321 ESCC individuals indicated that the somatically altered genes we found were significantly associated with ESCC poorer survival. Subsequently, we performed functional studies to validate the roles of the altered genes in tumor proliferation and metastasis.","abstract":"The genetic mechanisms underlying the poor prognosis of esophageal squamous cell carcinoma (ESCC) are not well understood. In this study, we comprehensively characterized somatic mutations, copy number alterations (SCNAs)/structural variants (SVs) found in ESCC from sequencing 10 whole-genome and 57 whole-exome matched tumor-normal pairs. We identified multiple somatic mutations seen previously in known cancer pathways and identified candidate genes for ESCC including VANGL1 and MIR4707. A survival analysis based on the expression profiles of 321 ESCC individuals indicated that the somatically altered genes we found were significantly associated with ESCC poorer survival. Subsequently, we performed functional studies to validate the roles of the altered genes in tumor proliferation and metastasis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-16T22:55:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001724","title":"2016_02_18_16_34_33_624_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001725","title":"2016_02_18_16_36_13_029_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001726","title":"HipSci whole exome sequencing for embryonic stem cell control lines","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we use commercially available embryonic stem cell lines as control samples against which to compare HipSci's iPS cell lines. We performed whole exome sequencing using Agilent whole exome pulldown method.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we use commercially available embryonic stem cell lines as control samples against which to compare HipSci's iPS cell lines. We performed whole exome sequencing using Agilent whole exome pulldown method.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-19T15:48:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001727","title":"HipSci RNA sequencing for embryonic stem cell control lines","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we perform RNA sequencing on commercially available embryonic stem cell lines as control samples against which to compare HipSci's iPS cell lines.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we perform RNA sequencing on commercially available embryonic stem cell lines as control samples against which to compare HipSci's iPS cell lines.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-19T15:52:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001728","title":"HipSci Methylation analysis for embryonic stem cell control lines","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we use commercially available embryonic stem cell lines as control samples against which to compare HipSci's iPS cell lines. We performed Methylation analysis using the Infinium HumanMethylation450 BeadChip.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we use commercially available embryonic stem cell lines as control samples against which to compare HipSci's iPS cell lines. We performed Methylation analysis using the Infinium HumanMethylation450 BeadChip.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-19T15:54:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001729","title":"HipSci expression microarray for embryonic stem cell control lines","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we use commercially available embryonic stem cell lines as control samples against which to compare HipSci's iPS cell lines. We performed expression analysis using the Illumina HumanHT -12 Expression BeadChip.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we use commercially available embryonic stem cell lines as control samples against which to compare HipSci's iPS cell lines. We performed expression analysis using the Illumina HumanHT -12 Expression BeadChip.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-19T15:56:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001730","title":"HipSci genotyping microarray for embryonic stem cell control lines","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we use commercially available embryonic stem cell lines as control samples against which to compare HipSci's iPS cell lines. We performed genotyping analysis using the Infinium HumanExome BeadChip.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we use commercially available embryonic stem cell lines as control samples against which to compare HipSci's iPS cell lines. We performed genotyping analysis using the Infinium HumanExome BeadChip.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-19T15:59:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001731","title":"RNA sequencing of 15 normal-tumor paired esophageal tumors and 3 esophageal cancer cell lines by Illumina sequencer.","description":"Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer mortality worldwide. We performed transcriptome sequencing of 15 ESCC tumor and normal paired samples, as well as 3 ESCC cell lines. We identified 4442 differentially expressed genes, including 1,930 up-regulated genes and 2,512 down-regulated genes in ESCCs. We found the deregulated genes commonly associated with several cancer-related pathways, of these, most significantly up-regulated enriched pathways were cell cycle and DNA replication. Meanwhile, genes expression involved metabolism cytochrome P450 pathway were frequently down-regulated in tumor tissue.Next, we found 163 cancer-specific RNA fusions in ESCC clinical and cell line samples, and SET was a recurrent 3’ partner gene involved in tumor-specific fusions. As a conclusion, we make a comprehensive profile of ESCC gene expression, and provide an integrated analysis with information of DNA genetic alterations.","abstract":"Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer mortality worldwide. We performed transcriptome sequencing of 15 ESCC tumor and normal paired samples, as well as 3 ESCC cell lines. We identified 4442 differentially expressed genes, including 1,930 up-regulated genes and 2,512 down-regulated genes in ESCCs. We found the deregulated genes commonly associated with several cancer-related pathways, of these, most significantly up-regulated enriched pathways were cell cycle and DNA replication. Meanwhile, genes expression involved metabolism cytochrome P450 pathway were frequently down-regulated in tumor tissue.Next, we found 163 cancer-specific RNA fusions in ESCC clinical and cell line samples, and SET was a recurrent 3’ partner gene involved in tumor-specific fusions. As a conclusion, we make a comprehensive profile of ESCC gene expression, and provide an integrated analysis with information of DNA genetic alterations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001732","title":"Novel mutational mechanisms and drivers in Pancreatic Neuroendocrine Tumours","description":"Pancreatic neuroendocrine tumours (PanNETs) are increasing in prevalence due to earlier detection, consequently creating challenges in clinical care, as current classification permits unsatisfactory therapeutic stratification. We performed whole genome sequencing of 102 primary PanNETs and defined the genomic events underlying their pathogenesis. We describe the mutational signatures they harbour, including a novel G:C&gt;T:A Base-Excision-Repair-deficiency signature due to MUTYH inactivation. We uncover a larger than expected proportion of germline mutations in clinically sporadic PanNETs. These include previously unreported mutations in DNA repair genes MUTYH, CHEK2, BRCA2, and PALB2, which together with MEN1 and VHL occur in 16% of patients. Somatic mutations (point mutations and structural rearrangements) commonly occurred in genes involved in 4 main pathways: chromatin remodelling, DNA damage repair, activation of mTOR signalling (including novel EWSR1 gene fusions) and telomere maintenance. Aberrations in these mechanisms are associated with subtypes of PanNET with potential clinical application for prognostic and therapeutic stratification.","abstract":"Pancreatic neuroendocrine tumours (PanNETs) are increasing in prevalence due to earlier detection, consequently creating challenges in clinical care, as current classification permits unsatisfactory therapeutic stratification. We performed whole genome sequencing of 102 primary PanNETs and defined the genomic events underlying their pathogenesis. We describe the mutational signatures they harbour, including a novel G:C&gt;T:A Base-Excision-Repair-deficiency signature due to MUTYH inactivation. We uncover a larger than expected proportion of germline mutations in clinically sporadic PanNETs. These include previously unreported mutations in DNA repair genes MUTYH, CHEK2, BRCA2, and PALB2, which together with MEN1 and VHL occur in 16% of patients. Somatic mutations (point mutations and structural rearrangements) commonly occurred in genes involved in 4 main pathways: chromatin remodelling, DNA damage repair, activation of mTOR signalling (including novel EWSR1 gene fusions) and telomere maintenance. Aberrations in these mechanisms are associated with subtypes of PanNET with potential clinical application for prognostic and therapeutic stratification.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-22T06:52:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001733","title":"120 individuals from the TEENAGE study (Ntalla et al., 2013) have been genotyped on the Illumina HumanCoreExome-12v1-1_A array. This is a population-based study of adolescents from the Attica region in Greece","description":"120 individuals from the TEENAGE study (Ntalla et al., 2013) have been genotyped on the Illumina HumanCoreExome-12v1-1_A array. This is a population-based study of adolescents from the Attica region in Greece","abstract":"120 individuals from the TEENAGE study (Ntalla et al., 2013) have been genotyped on the Illumina HumanCoreExome-12v1-1_A array. This is a population-based study of adolescents from the Attica region in Greece","study_type":"Other","pubmed_ids":[23347264,23399026],"external_links":null,"is_released":true,"released_date":"2016-02-22T11:55:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001734","title":"Exome_sequencing_of_Non_syndromic_Congenital_Heart_Defects","description":"tbc","abstract":"tbc","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-22T14:01:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001735","title":"IBD_Whole_Genome_Sequencing_Phase_1","description":"IBD Whole Genome Sequencing Phase 1","abstract":"IBD Whole Genome Sequencing Phase 1","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-22T15:58:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001736","title":"Elucidating the genomic architecture of Asian EGFR-mutant lung adenocarcinoma through multi-region exome sequencing","description":"EGFR-mutant lung adenocarcinomas (LUAD) display diverse clinical trajectories and are characterized by rapid but short-lived responses to EGFR tyrosine kinase inhibitors (TKIs). Through sequencing of 79 spatially distinct regions from 16 early stage tumors, we show that despite low mutation burdens, EGFR-mutant Asian LUADs unexpectedly exhibit a complex genomic landscape with frequent and early whole genome doubling, aneuploidy and high clonal diversity. Multiple truncal alterations, including TP53 mutations and loss of CDKN2A and RB1, converge on cell cycle dysregulation, with late sector-specific high amplitude amplifications and deletions that potentially beget drug resistant clones. We highlight the association between genomic architecture and clinical phenotypes, such as co-occurring truncal drivers and primary TKI resistance. Through comparative analysis with published smoking-related LUAD, we postulate that the high intra-tumor heterogeneity observed in Asian EGFR-mutant LUAD may be contributed by an early dominant driver, genomic instability and low background mutation rates.","abstract":"EGFR-mutant lung adenocarcinomas (LUAD) display diverse clinical trajectories and are characterized by rapid but short-lived responses to EGFR tyrosine kinase inhibitors (TKIs). Through sequencing of 79 spatially distinct regions from 16 early stage tumors, we show that despite low mutation burdens, EGFR-mutant Asian LUADs unexpectedly exhibit a complex genomic landscape with frequent and early whole genome doubling, aneuploidy and high clonal diversity. Multiple truncal alterations, including TP53 mutations and loss of CDKN2A and RB1, converge on cell cycle dysregulation, with late sector-specific high amplitude amplifications and deletions that potentially beget drug resistant clones. We highlight the association between genomic architecture and clinical phenotypes, such as co-occurring truncal drivers and primary TKI resistance. Through comparative analysis with published smoking-related LUAD, we postulate that the high intra-tumor heterogeneity observed in Asian EGFR-mutant LUAD may be contributed by an early dominant driver, genomic instability and low background mutation rates.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-24T08:15:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001737","title":"Exome-sequencing of two UFM individuals and their Fragile X family members.","description":"Fragile X syndrome (FXS) is a monogenic neurodevelopmental disease often caused by a CGG triplet expansion in the 5’UTR of the FMR1 gene, which results in DNA methylation of the FMR1 promoter and its transcriptional silencing. Exceptional healthy individuals named \"unmethylated full mutation (UFM)\" have been identified in the families of FX patients. They carry an expanded CGG repeat, but show normal FMR1 epigenetic configuration and expression. In this study we performed exome-sequencing of two UFM individuals and their family members to identify possible genetic mutations responsible for the escape of silencing in the unmethylated full mutation (UFM) phenotype.","abstract":"Fragile X syndrome (FXS) is a monogenic neurodevelopmental disease often caused by a CGG triplet expansion in the 5’UTR of the FMR1 gene, which results in DNA methylation of the FMR1 promoter and its transcriptional silencing. Exceptional healthy individuals named \"unmethylated full mutation (UFM)\" have been identified in the families of FX patients. They carry an expanded CGG repeat, but show normal FMR1 epigenetic configuration and expression. In this study we performed exome-sequencing of two UFM individuals and their family members to identify possible genetic mutations responsible for the escape of silencing in the unmethylated full mutation (UFM) phenotype.","study_type":"Other","pubmed_ids":[27840045],"external_links":null,"is_released":true,"released_date":"2016-02-25T12:28:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001738","title":"Multi-layered population structure in Island Southeast Asians","description":"The history of human settlement in Southeast Asia has been complex and involved several distinct dispersal events. Here we report the analyses of 1825 individuals from Southeast Asia including new genome-wide genotype data for 146 individuals from three Mainland Southeast Asian (Burmese, Malay and Vietnamese) and four Island Southeast Asian (Dusun, Filipino, Kankanaey and Murut) populations. While confirming the presence of previously recognized major ancestry components in the Southeast Asian population structure, we highlight the Kankanaey Igorots from the highlands of the Philippine Mountain Province as likely the closest living representatives of the source population that may have given rise to the Austronesianexpansion. This conclusion rests on independent evidence from various analyses of autosomal data and uniparental markers. Given the extensive presence of trade goods, cultural and linguistic evidence of Indian influence in Southeast Asia starting from 2.5kya we also detect traces of a South Asian signature in different populations in the region dating to the last couple of thousand years.","abstract":"The history of human settlement in Southeast Asia has been complex and involved several distinct dispersal events. Here we report the analyses of 1825 individuals from Southeast Asia including new genome-wide genotype data for 146 individuals from three Mainland Southeast Asian (Burmese, Malay and Vietnamese) and four Island Southeast Asian (Dusun, Filipino, Kankanaey and Murut) populations. While confirming the presence of previously recognized major ancestry components in the Southeast Asian population structure, we highlight the Kankanaey Igorots from the highlands of the Philippine Mountain Province as likely the closest living representatives of the source population that may have given rise to the Austronesianexpansion. This conclusion rests on independent evidence from various analyses of autosomal data and uniparental markers. Given the extensive presence of trade goods, cultural and linguistic evidence of Indian influence in Southeast Asia starting from 2.5kya we also detect traces of a South Asian signature in different populations in the region dating to the last couple of thousand years.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-26T15:53:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001740","title":"Nrf2 transcript alterations","description":"WGS and RNA-seq data for Nrf2 study","abstract":"WGS and RNA-seq data for Nrf2 study","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-02-26T20:36:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001741","title":"Searching for variants associated with endometriosis","description":"We explored regulatory mechanism of a SNP on chromosome 9p21 associated with endometriosis by leveraging “allele-specific” functional genomic approaches. By re-sequencing 1.29 Mb of 9p21 region and scrutinizing DNase-seq data from the ENCODE project, we prioritized rs17761446 as a candidate functional variant that was in perfect linkage disequilibrium with the original GWAS SNP (rs10965235) and located on DNase I hypersensitive site. Chromosome conformation capture followed by high-throughput sequencing revealed that the protective G allele of rs17761446 exerted stronger chromatin interaction with ANRIL promoter. We demonstrated that the protective allele exhibited preferential binding affinities to TCF7L2 and EP300 by bioinformatics and chromatin immunoprecipitation (ChIP) analyses. ChIP assays for histone H3 lysine 27 acetylation and RNA polymerase II reinforced the enhancer activity of the SNP site. The allele specific expression analysis for eutopic endometrial tissues and endometrial carcinoma cell lines showed that rs17761446 was a cis-regulatory variant where G allele was associated with increased ANRIL expression.","abstract":"We explored regulatory mechanism of a SNP on chromosome 9p21 associated with endometriosis by leveraging “allele-specific” functional genomic approaches. By re-sequencing 1.29 Mb of 9p21 region and scrutinizing DNase-seq data from the ENCODE project, we prioritized rs17761446 as a candidate functional variant that was in perfect linkage disequilibrium with the original GWAS SNP (rs10965235) and located on DNase I hypersensitive site. Chromosome conformation capture followed by high-throughput sequencing revealed that the protective G allele of rs17761446 exerted stronger chromatin interaction with ANRIL promoter. We demonstrated that the protective allele exhibited preferential binding affinities to TCF7L2 and EP300 by bioinformatics and chromatin immunoprecipitation (ChIP) analyses. ChIP assays for histone H3 lysine 27 acetylation and RNA polymerase II reinforced the enhancer activity of the SNP site. The allele specific expression analysis for eutopic endometrial tissues and endometrial carcinoma cell lines showed that rs17761446 was a cis-regulatory variant where G allele was associated with increased ANRIL expression.","study_type":"Other","pubmed_ids":[27055116],"external_links":null,"is_released":true,"released_date":"2016-03-02T11:34:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001742","title":"We performed whole exome sequencing (WES) using Hiseq on 22 paired CMLs. We also performed whole exome sequencing (WES) using CG on 88 paired CMLs. All the data belongs to CML in China - ICGC project.","description":"We performed whole exome sequencing (WES) using Hiseq on 22 paired CMLs. We also performed whole exome sequencing (WES) using CG on 88 paired CMLs.All the data belongs to CML in China - ICGC project.","abstract":"We performed whole exome sequencing (WES) using Hiseq on 22 paired CMLs. We also performed whole exome sequencing (WES) using CG on 88 paired CMLs.All the data belongs to CML in China - ICGC project.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-03-02T13:24:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001743","title":"ENU_CCK_81_cetuximab_pilot_project","description":"Cetuximab is a targeted monoclonal antibody against the epidermal growth factor receptor (EGFR) which is used therapeutically for the treatment of KRAS wild-type colorectal cancer (CRC). The Cetuximab sensitive KRAS wild-type CRC cell line NCI-H508 has been treated with a fixed concentration of ENU for 24 hours and then selected with Cetuximab until drug resistant clones were ready to be picked and grown up as sub-clones of the parental cell line. These will have genes causally implicated in cancer sequenced to identify common point mutations in multiple independently derived drug resistant clones as a forward genetic screen for mechanisms of resistance to Cetuximab in CRC.","abstract":"Pilot experiment with different concentrations of ENU used to engender resistance to Cetuximab in the KRAS wild-type colorectal cancer cell line CCK-81.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-03-02T14:44:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001744","title":"ENU_NCI_H508_cetuximab_fixed_concentration_project","description":"Cetuximab is a targeted monoclonal antibody against the epidermal growth factor receptor (EGFR) which is used therapeutically for the treatment of KRAS wild-type colorectal cancer (CRC). The Cetuximab sensitive KRAS wild-type CRC cell line NCI-H508 has been treated with a fixed concentration of ENU for 24 hours and then selected with Cetuximab until drug resistant clones were ready to be picked and grown up as sub-clones of the parental cell line. These will have genes causally implicated in cancer sequenced to identify common point mutations in multiple independently derived drug resistant clones as a forward genetic screen for mechanisms of resistance to Cetuximab in CRC","abstract":"Experiment with different concentrations of ENU used to engender resistance to Cetuximab in the KRAS wild-type colorectal cancer cell line NCI-H508.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-03-02T14:46:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001745","title":"ENU_NCI_H508_Cetuximab_SecondRound","description":"Cetuximab is a targeted monoclonal antibody against the epidermal growth factor receptor (EGFR) which is used therapeutically for the treatment of KRAS wild-type colorectal cancer (CRC). The Cetuximab sensitive KRAS wild-type CRC cell line NCI-H508 has been treated with a fixed concentration of ENU for 24 hours and then selected with Cetuximab until drug resistant clones were ready to be picked and grown up as sub-clones of the parental cell line. These will have genes causally implicated in cancer sequenced to identify common point mutations in multiple independently derived drug resistant clones as a forward genetic screen for mechanisms of resistance to Cetuximab in CRC","abstract":"Experiment to identify mechanisms of resistance to Cetuximab in colorectal cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-03-02T14:47:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001746","title":"Drug-perturbation-based stratification of blood cancer","description":"As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non–BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care.","abstract":"As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non–BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care.","study_type":"Other","pubmed_ids":[29227286],"external_links":null,"is_released":true,"released_date":"2016-03-03T10:11:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001747","title":"EGAS00001001747","description":null,"abstract":null,"study_type":"Other","pubmed_ids":[26681675],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001748","title":"Effect_of_live_attenuated_and_Inactivated_influenza_vaccines_on_experimental_human_pneumoccocal_carriage__transcriptional_response_pilot_","description":"In this pilot experiment we are profiling the transciptional reponse (in rhinoprobe nasal samples and blood samples) in 20 individuals who have been challenged with pneumococcus. Using the Experimental Human Pneumococcal Carraige (EHPC) model establish at the Liverpool School of Tropical Medicine by Prof Stephen Gordon and colleagues, carefully screened healthy adult volunteers are inoculated with doses of pneumococci – with a 50% acquisition rate at a density typical of natural carriage and a duration of  1 - 3 weeks. Nasal and blood samples are taken before (-5 days) and after (+2 days) this innoculation. We will perform RNA-sequencing of these samples to ascertain the transcriptional responses to the pneuomocci challenge and correlate variation in the response with carriage.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"In this pilot experiment we are profiling the transciptional reponse (in rhinoprobe nasal samples and blood samples) in 20 individuals who have been challenged with pneumococcus. Using the Experimental Human Pneumococcal Carraige (EHPC) model establish at the Liverpool School of Tropical Medicine by Prof Stephen Gordon and colleagues, carefully screened healthy adult volunteers are inoculated with doses of pneumococci – with a 50% acquisition rate at a density typical of natural carriage and a duration of  1 - 3 weeks. Nasal and blood samples are taken before (-5 days) and after (+2 days) this innoculation. We will perform RNA-sequencing of these samples to ascertain the transcriptional responses to the pneuomocci challenge and correlate variation in the response with carriage.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001749","title":"whole genome and whole exome sequencing of hepatocellular carinoma","description":"whole genome and whole exome sequencing of hepatocellular carinoma","abstract":"whole genome and whole exome sequencing of hepatocellular carinoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001750","title":"'Population-level analysis of gut microbiome variation'","description":"\"Here, we studied 1,106 well-phenotyped individuals from the Flemish Gut Flora Project (FGFP, Belgium; discovery)\"","abstract":"\"Here, we studied 1,106 well-phenotyped individuals from the Flemish Gut Flora Project (FGFP, Belgium; discovery)\"","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001001751","title":"An integrative model of pathway convergence in genetically heterogeneous blast crisis chronic myeloid leukemia (CML)","description":"Targeted therapies against the BCR-ABL1 kinase have revolutionized treatment of chronic phase (CP) chronic myeloid leukemia (CML). In contrast, management of blast crisis (BC) CML remains challenging because BC cells acquire complex molecular alterations that confer stemness features to progenitor populations and resistance to BCR-ABL1 tyrosine kinase inhibitors. Comprehensive models of BC transformation have proved elusive because of the rarity and genetic heterogeneity of BC, but are important for developing biomarkers predicting BC progression and effective therapies. To better understand BC, we performed an integrated multiomics analysis of 74 CP and BC samples using whole-genome and exome sequencing, transcriptome and methylome profiling, and chromatin immunoprecipitation followed by high-throughput sequencing. Employing pathway-based analysis, we found the BC genome was significantly enriched for mutations affecting components of the polycomb repressive complex (PRC) pathway. While transcriptomically, BC progenitors were enriched and depleted for PRC1- and PRC2-related gene sets respectively. By integrating our data sets, we determined that BC progenitors undergo PRC-driven epigenetic reprogramming toward a convergent transcriptomic state. Specifically, PRC2 directs BC DNA hypermethylation, which in turn silences key genes involved in myeloid differentiation and tumor suppressor function via so-called epigenetic switching, whereas PRC1 represses an overlapping and distinct set of genes, including novel BC tumor suppressors. On the basis of these observations, we developed an integrated model of BC that facilitated the identification of combinatorial therapies capable of reversing BC reprogramming (decitabine+PRC1 inhibitors), novel PRC-silenced tumor suppressor genes (NR4A2), and gene expression signatures predictive of disease progression and drug resistance in CP.","abstract":"Targeted therapies against the BCR-ABL1 kinase have revolutionized treatment of chronic phase (CP) chronic myeloid leukemia (CML). In contrast, management of blast crisis (BC) CML remains challenging because BC cells acquire complex molecular alterations that confer stemness features to progenitor populations and resistance to BCR-ABL1 tyrosine kinase inhibitors. Comprehensive models of BC transformation have proved elusive because of the rarity and genetic heterogeneity of BC, but are important for developing biomarkers predicting BC progression and effective therapies. To better understand BC, we performed an integrated multiomics analysis of 74 CP and BC samples using whole-genome and exome sequencing, transcriptome and methylome profiling, and chromatin immunoprecipitation followed by high-throughput sequencing. Employing pathway-based analysis, we found the BC genome was significantly enriched for mutations affecting components of the polycomb repressive complex (PRC) pathway. While transcriptomically, BC progenitors were enriched and depleted for PRC1- and PRC2-related gene sets respectively. By integrating our data sets, we determined that BC progenitors undergo PRC-driven epigenetic reprogramming toward a convergent transcriptomic state. Specifically, PRC2 directs BC DNA hypermethylation, which in turn silences key genes involved in myeloid differentiation and tumor suppressor function via so-called epigenetic switching, whereas PRC1 represses an overlapping and distinct set of genes, including novel BC tumor suppressors. On the basis of these observations, we developed an integrated model of BC that facilitated the identification of combinatorial therapies capable of reversing BC reprogramming (decitabine+PRC1 inhibitors), novel PRC-silenced tumor suppressor genes (NR4A2), and gene expression signatures predictive of disease progression and drug resistance in CP.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-03-10T07:02:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001752","title":"Dissection of the molecular complexity of colorectal cancer in pre-clinical models identifies predictive signatures of sensitivity to EGFR inhibitors","description":"Colorectal carcinoma (CRC) is a heterogeneous tumour entity, with only a fraction of the tumours responding to currently available therapies. A detailed understanding of the biology and genetics of CRC is a prerequisite for precision medicine. To address this challenge in clinical oncology, the OncoTrack consortium recruited 106 CRC patients (stages I-IV) and developed an integrated pre-clinical platform analysing drug sensitivity in the established matched patient-derived in vivo and in vitro models, 46 three-dimensional cell cultures and 59 xenografts, recapitulating many of the molecular features of the donor tumours. We generated extensive omics information on patient tumours and their derived models used to generate a compendium of drug sensitivity data. We could distinguish tumour molecular sub-groups responding differently to therapy and identified a novel independent predictor of sensitivity to the EGFR inhibitor cetuximab. The findings reported here will advance our understanding of CRC and its response to therapy.","abstract":"Colorectal carcinoma (CRC) is a heterogeneous tumour entity, with only a fraction of the tumours responding to currently available therapies. A detailed understanding of the biology and genetics of CRC is a prerequisite for precision medicine. To address this challenge in clinical oncology, the OncoTrack consortium recruited 106 CRC patients (stages I-IV) and developed an integrated pre-clinical platform analysing drug sensitivity in the established matched patient-derived in vivo and in vitro models, 46 three-dimensional cell cultures and 59 xenografts, recapitulating many of the molecular features of the donor tumours. We generated extensive omics information on patient tumours and their derived models used to generate a compendium of drug sensitivity data. We could distinguish tumour molecular sub-groups responding differently to therapy and identified a novel independent predictor of sensitivity to the EGFR inhibitor cetuximab. The findings reported here will advance our understanding of CRC and its response to therapy.","study_type":"Other","pubmed_ids":[28186126],"external_links":null,"is_released":true,"released_date":"2016-03-11T09:02:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001753","title":"METABRIC: Data from Pereira et al (2016), The somatic mutation profiles of 2433 breast cancers refine their genomic and transcriptomic landscapes. Nat Comms 7.","description":"The genomic landscape of breast cancer is complex, and inter- and intra-tumour heterogeneity are important challenges in treating the disease.  In this study, we sequence 173 genes in 2433 primary breast tumours that have copy number aberration (CNA), gene expression, and long-term clinical follow-up data.  We identify 40 mutation-driver (Mut-driver) genes, and determine associations between mutations, driver CNA profiles, clinical-pathological parameters, and survival.  We assess the clonal states of Mut-driver mutations, and estimate levels of intratumour heterogeneity using mutant allele fractions.   Associations between PIK3CA mutations and reduced survival are identified in three subgroups of ER-positive cancer (defined by amplification of 17q23, 11q13-14 or 8q24).  High levels of intratumour heterogeneity are in general associated with worse outcome, but highly aggressive tumours with 11q13-14 amplification have low levels of intratumour heterogeneity.  These results emphasise the importance of genome-based stratification of breast cancer, and have important implications for designing therapeutic strategies.","abstract":"The genomic landscape of breast cancer is complex, and inter- and intra-tumour heterogeneity are important challenges in treating the disease.  In this study, we sequence 173 genes in 2433 primary breast tumours that have copy number aberration (CNA), gene expression, and long-term clinical follow-up data.  We identify 40 mutation-driver (Mut-driver) genes, and determine associations between mutations, driver CNA profiles, clinical-pathological parameters, and survival.  We assess the clonal states of Mut-driver mutations, and estimate levels of intratumour heterogeneity using mutant allele fractions.   Associations between PIK3CA mutations and reduced survival are identified in three subgroups of ER-positive cancer (defined by amplification of 17q23, 11q13-14 or 8q24).  High levels of intratumour heterogeneity are in general associated with worse outcome, but highly aggressive tumours with 11q13-14 amplification have low levels of intratumour heterogeneity.  These results emphasise the importance of genome-based stratification of breast cancer, and have important implications for designing therapeutic strategies.","study_type":"Other","pubmed_ids":[27161491],"external_links":null,"is_released":true,"released_date":"2016-03-13T15:39:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001754","title":"Inferring expressed genes by whole-genome sequencing of plasma DNA","description":"The analysis of cell-free DNA (cfDNA) in plasma represents a rapidly advancing field in medicine. cfDNA consists predominantly of nucleosome-protected DNA shed into the bloodstream by cells undergoing apoptosis. We performed whole-genome sequencing (WGS) of plasma DNA and identified two discrete regions at transcription start sites (TSS) where the nucleosome occupancy results in different read-depth coverage patterns in expressed and silent genes. By employing machine learning for gene classification we found that the plasma DNA read depth patterns from healthy donors reflected the expression signature of hematopoietic cells. In cancer patients with metastatic disease, we were able to classify expressed cancer driver genes in regions with somatic copy number gains with high accuracy. We could even determine the expressed isoform of genes with several TSSs as confirmed by RNA-Seq of the matching primary tumor. Our analyses provide functional information about the cells releasing their DNA into the circulation.","abstract":"The analysis of cell-free DNA (cfDNA) in plasma represents a rapidly advancing field in medicine. cfDNA consists predominantly of nucleosome-protected DNA shed into the bloodstream by cells undergoing apoptosis. We performed whole-genome sequencing (WGS) of plasma DNA and identified two discrete regions at transcription start sites (TSS) where the nucleosome occupancy results in different read-depth coverage patterns in expressed and silent genes. By employing machine learning for gene classification we found that the plasma DNA read depth patterns from healthy donors reflected the expression signature of hematopoietic cells. In cancer patients with metastatic disease, we were able to classify expressed cancer driver genes in regions with somatic copy number gains with high accuracy. We could even determine the expressed isoform of genes with several TSSs as confirmed by RNA-Seq of the matching primary tumor. Our analyses provide functional information about the cells releasing their DNA into the circulation.","study_type":"Other","pubmed_ids":[27571261],"external_links":null,"is_released":true,"released_date":"2016-03-14T07:38:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001755","title":"Transcriptomes_of_human_lymphocytes","description":"In this study we will compare the single cell transcriptomes of immune cells from asthmatics responding to steroids, those refractory to steroids, and a control population.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"About one in 12 people are thought to be affected by allergic asthma, which can be a life-threatening condition. Steroids are effective in most patients, but unfortunately a small minority is refractory to steroids. By dissecting immune cell populations in asthma patient groups at single cell resolution, we will gain insight into novel therapeutic targets and pathways for steroid-refractory asthma","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-03-15T15:36:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001756","title":"WTCCC2 Bacteraemia Susceptibility (BS) samples","description":"A WTCCC2 project genome-wide association study for bacteraemia susceptibility in 4924 individuals from Kenya, genotyped on the Affymetrix 6.0 array.","abstract":"A WTCCC2 project genome-wide association study for bacteraemia susceptibility in 4924 individuals from Kenya, genotyped on the Affymetrix 6.0 array.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-03-21T16:55:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001757","title":"Evolutionary Genome Analysis of Transformation into Small Cell Carcinomas from Lung Adenocarcinomas","description":"Anecdotal case have been reported lung adenocarcinoma could occasionally transform into small cell carcinoma. Most of the reported cases were EGFR-mutant lung adenocarcinomas that transform into small cell carcinoma during EGFR tyrosine kinase inhibitor treatment. However, some cases also indicate lung adenocarcinomas without EGFR mutation could also transform into small cell carcinomas. Here we investigate this transformation process by whole genome sequencing of transformed small cell carcinomas as well as serially acquired samples of lung adenocarcinoma into small cell carcinomas.","abstract":"Anecdotal case have been reported lung adenocarcinoma could occasionally transform into small cell carcinoma. Most of the reported cases were EGFR-mutant lung adenocarcinomas that transform into small cell carcinoma during EGFR tyrosine kinase inhibitor treatment. However, some cases also indicate lung adenocarcinomas without EGFR mutation could also transform into small cell carcinomas. Here we investigate this transformation process by whole genome sequencing of transformed small cell carcinomas as well as serially acquired samples of lung adenocarcinoma into small cell carcinomas.","study_type":"Other","pubmed_ids":[28498782],"external_links":null,"is_released":true,"released_date":"2016-03-22T01:16:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001001758","title":"Whole genome sequencing data of 20 bladder cancer samples (tumor & normal)","description":"We collected 20 patients with urothelial bladder carcinoma including 15 invasive bladder cancer and 5 superficial bladder cancer. Tumor samples with matched peripheral blood were obtained from individuals, and each subject was properly informed before recruitment for the study, according to the regulations of the institutional ethics review boards. Genomic DNA from tumor and matched peripheral blood samples was isolated using QIAamp DNA Mini kits (Qiagen), and DNA libraries were constructed according to the protocol provided by the manufacturer (Illumina). Whole genome sequencing data were generated using the Illumina HiSeq 2000 platform in 2 × 90-bp paired-end reads. The mean sequencing depth of all samples was 36.83×.","abstract":"We collected 20 patients with urothelial bladder carcinoma including 15 invasive bladder cancer and 5 superficial bladder cancer. Tumor samples with matched peripheral blood were obtained from individuals, and each subject was properly informed before recruitment for the study, according to the regulations of the institutional ethics review boards. Genomic DNA from tumor and matched peripheral blood samples was isolated using QIAamp DNA Mini kits (Qiagen), and DNA libraries were constructed according to the protocol provided by the manufacturer (Illumina). Whole genome sequencing data were generated using the Illumina HiSeq 2000 platform in 2 × 90-bp paired-end reads. The mean sequencing depth of all samples was 36.83×.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001759","title":"Whole genome sequencing data of 20 clear cell renal cell carcinoma samples (tumor & normal)","description":"We collected 20 patients with clear cell renal cell carcinoma which includes Papillary renal cell carcinoma, Renal clear cell adenocarcinoma (sugar tumor), NOS, Chromophobe cell carcinoma, Transitional cell carcinoma, Granular renal cell carcinoma with clear cell components, Papillary adenocarcinoma, Level 2 clear cell carcinoma, Right renal clear cell carcinoma, Left renal cell carcinoma, Clear cell carcinoma. Tumor samples with morphologically adjacent normal kidney tissues were obtained from individuals, and each subject was properly informed before recruitment for the study, according to the regulations of the institutional ethics review boards. Genomic DNA from tumor and morphologically adjacent normal kidney tissues samples was isolated using QIAamp DNA Mini kits (Qiagen), and DNA libraries were constructed according to the protocol provided by the manufacturer (Illumina). Whole genome sequencing data were generated using the Illumina HiSeq 2000 platform in 2 × 90-bp paired-end reads. The mean sequencing depth of all samples was about 25×.","abstract":"We collected 20 patients with clear cell renal cell carcinoma which includes Papillary renal cell carcinoma, Renal clear cell adenocarcinoma (sugar tumor), NOS, Chromophobe cell carcinoma, Transitional cell carcinoma, Granular renal cell carcinoma with clear cell components, Papillary adenocarcinoma, Level 2 clear cell carcinoma, Right renal clear cell carcinoma, Left renal cell carcinoma, Clear cell carcinoma. Tumor samples with morphologically adjacent normal kidney tissues were obtained from individuals, and each subject was properly informed before recruitment for the study, according to the regulations of the institutional ethics review boards. Genomic DNA from tumor and morphologically adjacent normal kidney tissues samples was isolated using QIAamp DNA Mini kits (Qiagen), and DNA libraries were constructed according to the protocol provided by the manufacturer (Illumina). Whole genome sequencing data were generated using the Illumina HiSeq 2000 platform in 2 × 90-bp paired-end reads. The mean sequencing depth of all samples was about 25×.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001760","title":"Subjects with founder mutation causing leukoencephalopathy","description":"Genetic leukoencephalopathies (gLEs) are a group of heterogeneous disorders with white matter abnormalities in the central nervous system (CNS). Patients affected with gLEs have brain white matter defects that can be seen in MRI and exhibit variable neurologic phenotypes including motor impairment, hypotonia, pyramidal dysfunction, dystonia and/or dyskinesias, ataxia, seizures, cortical blindness, optic atrophy, and impaired cognitive development. The exact causes in half of gLEs are unknown. We studied three unrelated families affected with an undiagnosed gLE and discovered a homozygous germline mutation c.2536T&gt;G in VPS11 by whole exome sequencing, a gene involved in membrane trafficking and fusion of the lysosomes and endosomes, as a novel cause of a new gLE syndrome.","abstract":"Genetic leukoencephalopathies (gLEs) are a group of heterogeneous disorders with white matter abnormalities in the central nervous system (CNS). Patients affected with gLEs have brain white matter defects that can be seen in MRI and exhibit variable neurologic phenotypes including motor impairment, hypotonia, pyramidal dysfunction, dystonia and/or dyskinesias, ataxia, seizures, cortical blindness, optic atrophy, and impaired cognitive development. The exact causes in half of gLEs are unknown. We studied three unrelated families affected with an undiagnosed gLE and discovered a homozygous germline mutation c.2536T&gt;G in VPS11 by whole exome sequencing, a gene involved in membrane trafficking and fusion of the lysosomes and endosomes, as a novel cause of a new gLE syndrome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001761","title":"Genetics_of_congenital_anosmia_3","description":"Individuals with congenital anosmia are born lacking a sense of smell. Here we obtained genomic DNA from families with multiple individuals with anosmia, suggesting they are congenital. These include those inherited in a manner consistent with dominant and recessive alleles. We have sequenced the exomes of both affected and unaffected family members on the Illumina platform.","abstract":"Here we sequence the exomes of 3 individuals with congenital anosmia, plus 5 unaffected controls from the same families, on the Illumina Hiseq platform.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001763","title":"Longitudinal RNA-seq (whole blood) in a twin cohort","description":"The dataset consists of 232 RNA-seq samples (whole blood) obtained from healthy female from the TwinsUK adult registry cohort. The samples were obtained at two time points separated on average by 22 months.","abstract":"The dataset consists of 232 RNA-seq samples (whole blood) obtained from healthy female from the TwinsUK adult registry cohort. The samples were obtained at two time points separated on average by 22 months.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-03-30T15:04:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001764","title":"The_mutational_landscape_of_recurrent_Glioblastome_multiforme","description":"Targeted gene screen of approx 120 patients with primary GBM and recurrent samples.","abstract":"Targeted gene screen of approx 120 patients with primary GBM and recurrent samples.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-03-30T16:21:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001765","title":"Targeted_analysis_of_chondrosarcoma_cancer_genes","description":"Targeted analysis of chondrosarcoma cancer genes","abstract":"Targeted analysis of chondrosarcoma cancer genes","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-03-30T16:23:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001766","title":"A Genomic History of Aboriginal Australia","description":"The population history of Aboriginal Australians remains largely uncharacterised. We generated high-coverage genomes for 83 Aboriginal Australians (speakers of Pama-Nyungan languages) and 25 Papuans from the New Guinea Highlands. We find that Papuan and Aboriginal Australian ancestors diversified 25-40 thousand years ago (kya), suggesting early population structure in the ancient continent of Sahul (Australia, New Guinea and Tasmania). However, all studied Aboriginal Australians descend from a single founding population that differentiated ~10-32 kya. We infer a population expansion in northeast Australia during the Holocene (past c.10 kya) associated with limited gene flow from this region to the rest of Australia consistent with the spread of the Pama-Nyungan languages. We estimate that Aboriginal Australians and Papuans diverged from Eurasians 51-72 kya, following a single out of Africa dispersal, and subsequently admixed with different archaic populations. Finally, we report evidence of selection in Aboriginal Australians potentially associated with living in the desert.","abstract":"The population history of Aboriginal Australians remains largely uncharacterised. We generated high-coverage genomes for 83 Aboriginal Australians (speakers of Pama-Nyungan languages) and 25 Papuans from the New Guinea Highlands. We find that Papuan and Aboriginal Australian ancestors diversified 25-40 thousand years ago (kya), suggesting early population structure in the ancient continent of Sahul (Australia, New Guinea and Tasmania). However, all studied Aboriginal Australians descend from a single founding population that differentiated ~10-32 kya. We infer a population expansion in northeast Australia during the Holocene (past c.10 kya) associated with limited gene flow from this region to the rest of Australia consistent with the spread of the Pama-Nyungan languages. We estimate that Aboriginal Australians and Papuans diverged from Eurasians 51-72 kya, following a single out of Africa dispersal, and subsequently admixed with different archaic populations. Finally, we report evidence of selection in Aboriginal Australians potentially associated with living in the desert.","study_type":"Other","pubmed_ids":[27654914],"external_links":null,"is_released":true,"released_date":"2016-03-30T18:33:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001767","title":"Ashkenazi Jewish Leukoencephalopathy","description":"Genetic leukoencephalopathies (gLEs) are a group of heterogeneous disorders with white matter abnormalities in the central nervous system (CNS). Patients affected with gLEs have brain white matter defects that can be seen in MRI and exhibit variable neurologic phenotypes including motor impairment, hypotonia, pyramidal dysfunction, dystonia and/or dyskinesias, ataxia, seizures, cortical blindness, optic atrophy, and impaired cognitive development. The exact causes in half of gLEs are unknown. We studied three unrelated families affected with an undiagnosed gLE and discovered a homozygous germline mutation c.2536T&gt;G in VPS11 by whole exome sequencing, a gene involved in membrane trafficking and fusion of the lysosomes and endosomes, as a novel cause of a new gLE syndrome.","abstract":"Genetic leukoencephalopathies (gLEs) are a group of heterogeneous disorders with white matter abnormalities in the central nervous system (CNS). Patients affected with gLEs have brain white matter defects that can be seen in MRI and exhibit variable neurologic phenotypes including motor impairment, hypotonia, pyramidal dysfunction, dystonia and/or dyskinesias, ataxia, seizures, cortical blindness, optic atrophy, and impaired cognitive development. The exact causes in half of gLEs are unknown. We studied three unrelated families affected with an undiagnosed gLE and discovered a homozygous germline mutation c.2536T&gt;G in VPS11 by whole exome sequencing, a gene involved in membrane trafficking and fusion of the lysosomes and endosomes, as a novel cause of a new gLE syndrome.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-03-30T20:33:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001768","title":"Ashkenazi Jewish Leukoencephalopathy2","description":"Genetic leukoencephalopathies (gLEs) are a group of heterogeneous disorders with white matter abnormalities in the central nervous system (CNS). Patients affected with gLEs have brain white matter defects that can be seen in MRI and exhibit variable neurologic phenotypes including motor impairment, hypotonia, pyramidal dysfunction, dystonia and/or dyskinesias, ataxia, seizures, cortical blindness, optic atrophy, and impaired cognitive development. The exact causes in half of gLEs are unknown. We studied three unrelated families affected with an undiagnosed gLE and discovered a homozygous germline mutation c.2536T&gt;G in VPS11 by whole exome sequencing, a gene involved in membrane trafficking and fusion of the lysosomes and endosomes, as a novel cause of a new gLE syndrome.","abstract":"Genetic leukoencephalopathies (gLEs) are a group of heterogeneous disorders with white matter abnormalities in the central nervous system (CNS). Patients affected with gLEs have brain white matter defects that can be seen in MRI and exhibit variable neurologic phenotypes including motor impairment, hypotonia, pyramidal dysfunction, dystonia and/or dyskinesias, ataxia, seizures, cortical blindness, optic atrophy, and impaired cognitive development. The exact causes in half of gLEs are unknown. We studied three unrelated families affected with an undiagnosed gLE and discovered a homozygous germline mutation c.2536T&gt;G in VPS11 by whole exome sequencing, a gene involved in membrane trafficking and fusion of the lysosomes and endosomes, as a novel cause of a new gLE syndrome.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001774","title":"Korea Epigenome Project(KEP), Korea National Research Institute of Health(KNIH)","description":"The KEP was launched in 2012 to produce 50 epigenomic sets on Korean chronic diseases related target cells with the participation on Internationsl Human Epigenome Consortium(IHEC) of which focus is constructing 1000 reference epigenome map on 250 human cell type. The objective of the KEP was to provide a comprehensive epigenomic map of Korean chronic disease-related target tissues.\nSingle cells were isolated from the pancreas, fat and kidney. Islet, ductal, acinar, and beta cells from the pancreas were purified into a single homogenous cell type using flow-assisted cell sorting technique. Adipocytes and pre-adipocytes were purified from fat, using Percoll gradient centrifugation technique. Mesangial, distal tubule, proximal tubule, podocytes, and collecting duct cells from the kidney were collected using mechanical sieving and immunostaining methods. Each cell type was derived from normal tissue or those with diabetes, obesity, or chronic kidney disease.\nSixty reference epigenome datasets of pancreatic, fat, kidney cells were produced. Cell types such as the islets, and beta from the pancreas, adipocytes, pre-adipocytes from fat tissue, podocyte, mesangial, tubules from kidney were used for primary target to produce a Korean metabolic reference epigenome. And the bisulfite converted-whole genome sequencing, Infinium 450k DNA methylation bead array, mRNA, miRNA-Sequencing were performed to produce a comprehensive epigenomic map.\nThe aim of roadmap reports is preparation of Long-term and Mid-term Technology Roadmaps for Korean Human Epigenome Project towards a competitive execution of International Epigenome Project and successful expansion of the research outcomes. Roadmap reports reviewed on recent technological development of DNA methylation and histone modification analysis, emerging new trends in epigenome medicine, plans for hardware and software analysis systems aimed to epigenome analysis, medical expert  opinion on target cells and isolation scheme, bioinformatics expert  opinion on analytical tools, new ideas for a putative epigenome studies, trends in single cell epigenome analysis. In conclusion, roadmap report suggested several projects for the future KNIH epigenome research in collaboration with epigenome research group. These are including refocusing the goals of KNIH-driven research in identification of disease mechanism, development of new studies on GWAS-EWA, higher priority on the epigenomic studies of human primary cells, establishment of collaborative relationship with tissue banking centers, establishment of mapping centers and data analysis portals, establishment of Korean Epigenome Research Consortium, establishment of steering committee governing both research and funding, launching of additional funding for epigenomic researches.","abstract":"The KEP was launched in 2012 to produce 50 epigenomic sets on Korean chronic diseases related target cells with the participation on Internationsl Human Epigenome Consortium(IHEC) of which focus is constructing 1000 reference epigenome map on 250 human cell type. The objective of the KEP was to provide a comprehensive epigenomic map of Korean chronic disease-related target tissues.\nSingle cells were isolated from the pancreas, fat and kidney. Islet, ductal, acinar, and beta cells from the pancreas were purified into a single homogenous cell type using flow-assisted cell sorting technique. Adipocytes and pre-adipocytes were purified from fat, using Percoll gradient centrifugation technique. Mesangial, distal tubule, proximal tubule, podocytes, and collecting duct cells from the kidney were collected using mechanical sieving and immunostaining methods. Each cell type was derived from normal tissue or those with diabetes, obesity, or chronic kidney disease.\nSixty reference epigenome datasets of pancreatic, fat, kidney cells were produced. Cell types such as the islets, and beta from the pancreas, adipocytes, pre-adipocytes from fat tissue, podocyte, mesangial, tubules from kidney were used for primary target to produce a Korean metabolic reference epigenome. And the bisulfite converted-whole genome sequencing, Infinium 450k DNA methylation bead array, mRNA, miRNA-Sequencing were performed to produce a comprehensive epigenomic map.\nThe aim of roadmap reports is preparation of Long-term and Mid-term Technology Roadmaps for Korean Human Epigenome Project towards a competitive execution of International Epigenome Project and successful expansion of the research outcomes. Roadmap reports reviewed on recent technological development of DNA methylation and histone modification analysis, emerging new trends in epigenome medicine, plans for hardware and software analysis systems aimed to epigenome analysis, medical expert  opinion on target cells and isolation scheme, bioinformatics expert  opinion on analytical tools, new ideas for a putative epigenome studies, trends in single cell epigenome analysis. In conclusion, roadmap report suggested several projects for the future KNIH epigenome research in collaboration with epigenome research group. These are including refocusing the goals of KNIH-driven research in identification of disease mechanism, development of new studies on GWAS-EWA, higher priority on the epigenomic studies of human primary cells, establishment of collaborative relationship with tissue banking centers, establishment of mapping centers and data analysis portals, establishment of Korean Epigenome Research Consortium, establishment of steering committee governing both research and funding, launching of additional funding for epigenomic researches.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-04-04T01:54:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001775","title":"Ancient_DNA_from_Bronze_Age_Lebanon","description":"We propose to investigate ancient DNA from a Bronze Age site in the Near East. We have prepared 15 libraries and we plan to (1) scan for endogenous ancient DNA presence using 2 runs on MiSeq or 2 lanes of HiSeq rapid, (2) select top promising libraries and proceed to sequencing additional 20 lanes on HiSeq. We aim to obtain a final ~1x coverage of endogenous DNA from 5-8 samples for comparisons with published ancient and modern genomes.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Ancient DNA (aDNA) studies can describe the human past with exceptional details revealing how historical events have shaped the human genome through migration, mixture and selection. We have sequenced ancient genomes from Bronze Age Sidon- a Mediterranean city in the Near East in present-day Lebanon. The Bronze Age in the Near East was a period marked by important technological innovations which triggered major population expansions and mixing. We analyze aDNA from this period and refine our understanding of the events leading to the observed genetic diversity in the Near East and surrounding regions including East Africa and Europe.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001776","title":"10x_PRMD9_Son","description":"Whole-genome 10x Genomics sequencing one individual whose mother has a PRMD9 LoF genotype. The sample was sequenced previously by 10x using the same technology. We will evaluate the performance of the technology in house. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Whole-genome 10x Genomics sequencing one individual whose mother has a PRMD9 LoF genotype. The sample was sequenced previously by 10x using the same technology. We will evaluate the performance of the technology in house.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001777","title":"ENU_LS_411N_TripleTherapy","description":"BRAF V600E colorectal cancers do not respond to the only currently FDA approved targeted therapy for CRC. There is currently a trial underway in the UK recruiting V600E CRC patients for treatment with a triple therapy combination of Cetuximab, Trametinib and Dabrafenib. We have mutagenized a pool of V600E CRC cell lines and treated with this triple therapy to select out drug resistant clones. We will now sequence these drug resistant clones with the aim of identifying common point mutations engendering resistance to this new therapy.","abstract":"Experiment to identify mechanisms of resistance to a triple targeted therapy for BRAF V600E colorectal cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-04-12T13:11:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001778","title":"ENU_HT_29_BRAF_Triple_Therapy_Clones","description":"KRAS mutant CRC is currently in clinical trial with a combination of a MEK and Akt inhibitor. These patients will likely develop resistance to this combination. We aim to identify the mechanisms of resistance via ENU mutagenesis, with a view to identifying additional therapeutics which have the ability to overcome this resistance.","abstract":"ENU used to engender resistance to a combination of a MEK inhibitor and an Akt Inhibitor, expanded and characterised as separate clones.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-04-12T13:13:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001779","title":"AML clonal phylogeny","description":"Study of AMl clonal phylogeny. Fastq files from targeted resequencing and from exome sequencing from AML patients at diagnosis, complete remission or relapse time.","abstract":"Study of AMl clonal phylogeny. Fastq files from targeted resequencing and from exome sequencing from AML patients at diagnosis, complete remission or relapse time.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-04-13T13:51:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001780","title":"V2_panel_bait_design_test","description":"This study comprises of three different datasets. 1) 57 samples from the 1243 canapps cell line study,2) 91 FFPE normal samples and 3) 87 samples from the SCORT WS2 dataset. The aim is to sequence these 235 samples in order to test the new V2 Colorectal bait design.","abstract":"S-CORT will utilise clinically annotated pathological samples  to: 1. develop new predictive  tests, with a particular focus on mCRC/rectal cancer; 2. address 4 highly relevant clinical questions: 1. Can we predict which patients will respond to oxaliplatin treatment?2. Can we predict which patients respond to standard  or modified radiotherapy (RT) strategies? 3. Does stratification in early rectal/colon cancer predict risk of  invasion, thus informing either radical  or organ preserving treatment options?  4. Can we develop better biomarkers to predict response to novel molecularly guided approaches in stratified CRC cohorts?","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-04-14T10:28:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001781","title":"Genomics_of_methotrexate_resistance_in_HeLa","description":"Study of HeLa subclones exposed to methotrexate to generate resistance.","abstract":"Study of HeLa subclones exposed to methotrexate to generate resistance. The sequenced samples show a range of different mechanisms of resistance, including double minutes &amp; homogeneously staining regions for the DHFR gene; gain of 5q, and unknown mechanisms.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001001782","title":"Mitochondrial-Nuclear Mutational Cross-Talk Drives Recurrence of Localized Prostate Cancer","description":"Prostate cancer remains the most prevalent non-skin cancer in men, but has a remarkably quiet mutational profile. Exome sequencing studies have revealed few recurrent somatic single nucleotide variants (SNVs). Whole-genome sequencing studies have not yet identified highly recurrent driver non-coding SNVs (ncSNVs) or genomic rearrangements (Grs). As a result, the underlying events that drive this frequent disease remain unknown. While mitochondrial mutations have been linked to several tumour types, including prostate cancer, their global frequency and impact has remained unknown. To determine if mitochondrial mutations might drive some prostate cancers, we analyzed the mitochondrial genomes of 216 tumours from patients with the most commonly diagnosed form of prostate cancer. We developed a pipeline that conservatively identified only mitochondrial SNVs (mitoSNVs) that differed in the heteroplasmy fraction as compared to their paired-normal by at least 20%. We identified several features of the mitochondrial genome that were correlated with nuclear genomic mutations, as well as features that were significantly associated with biochemical recurrence.","abstract":"Prostate cancer remains the most prevalent non-skin cancer in men, but has a remarkably quiet mutational profile. Exome sequencing studies have revealed few recurrent somatic single nucleotide variants (SNVs). Whole-genome sequencing studies have not yet identified highly recurrent driver non-coding SNVs (ncSNVs) or genomic rearrangements (Grs). As a result, the underlying events that drive this frequent disease remain unknown. While mitochondrial mutations have been linked to several tumour types, including prostate cancer, their global frequency and impact has remained unknown. To determine if mitochondrial mutations might drive some prostate cancers, we analyzed the mitochondrial genomes of 216 tumours from patients with the most commonly diagnosed form of prostate cancer. We developed a pipeline that conservatively identified only mitochondrial SNVs (mitoSNVs) that differed in the heteroplasmy fraction as compared to their paired-normal by at least 20%. We identified several features of the mitochondrial genome that were correlated with nuclear genomic mutations, as well as features that were significantly associated with biochemical recurrence.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-04-14T18:44:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001783","title":"Genome sequencing of HCC from a Chinese cohort","description":"project aims to understand somatic variants, differential expressed genes and signaling pathways in HBV- and NASH related HCC tumors.","abstract":"project aims to understand somatic variants, differential expressed genes and signaling pathways in HBV- and NASH related HCC tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-04-15T03:16:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001784","title":"Analysis of tumor periphery and center-specific mutations in renal cell carcinoma","description":"Renal cell carcinoma (RCC) is a genomically heterogeneous tumor. In the present project, the question whether intratumoral heterogeneity follows a zonal pattern indicating spatial niches was addressed. Whole exome sequencing of 16 paired samples from tumor periphery and center revealed a number of region-specific functional SNVs and Indels. Therefore, RCCs are not composed of evenly admixed tumor cells but show topological differences in their clonal composition.","abstract":"Renal cell carcinoma (RCC) is a genomically heterogeneous tumor. In the present project, the question whether intratumoral heterogeneity follows a zonal pattern indicating spatial niches was addressed. Whole exome sequencing of 16 paired samples from tumor periphery and center revealed a number of region-specific functional SNVs and Indels. Therefore, RCCs are not composed of evenly admixed tumor cells but show topological differences in their clonal composition.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-04-19T11:18:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001785","title":"Whole exome sequencing of cancer and matched germline DNA from a UK cohort of Penile cancers.","description":"Other than an association with HPV infection, little is known about the genetic alterations determining the development of penile cancer (PeCa). While PeCa is rare in the developed world, it presents a significant burden in developing countries. Here we report the findings of whole exome sequencing (WES) to determine the somatic mutational landscape of PeCa. WES was performed on PeCa and matched germline DNA from 27 patients undergoing surgical resection. . Exome capture was performed using 50ng of tumour or matched germline DNA. Library preparation was performed using the Illumina TrueSeq or Nextrea exome capture kit according to the manufactures guidelines (Ilumina, San Diego, CA, USA). Samples underwent paired end sequencing on a Hi-Seq2000 platform with 100bp read length.","abstract":"Other than an association with HPV infection, little is known about the genetic alterations determining the development of penile cancer (PeCa). While PeCa is rare in the developed world, it presents a significant burden in developing countries. Here we report the findings of whole exome sequencing (WES) to determine the somatic mutational landscape of PeCa. WES was performed on PeCa and matched germline DNA from 27 patients undergoing surgical resection. . Exome capture was performed using 50ng of tumour or matched germline DNA. Library preparation was performed using the Illumina TrueSeq or Nextrea exome capture kit according to the manufactures guidelines (Ilumina, San Diego, CA, USA). Samples underwent paired end sequencing on a Hi-Seq2000 platform with 100bp read length.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001786","title":"Biallelic missense mutations in NSMCE3, encoding a subunit of the SMC5/6 complex, cause a chromosome breakage syndrome with severe lung disease","description":"We describe a new chromosome breakage syndrome associated with severe lung disease in early childhood. Four children from two unrelated kindreds died during infancy of severe pulmonary disease following viral pneumonia with evidence of combined T- and B-cell immunodeficiency. Whole exome sequencing revealed biallelic missense mutations in the NSMCE3 gene encoding a subunit of the SMC5/6 complex, essential for DNA damage response and chromosome segregation. The NSMCE3 mutations disrupt interactions within the SMC5/6 complex, leading to destabilization of the complex. Patient cells showed chromosome rearrangements, micronuclei, sensitivity to replication stress and DNA damage, and defective homologous recombination.","abstract":"We describe a new chromosome breakage syndrome associated with severe lung disease in early childhood. Four children from two unrelated kindreds died during infancy of severe pulmonary disease following viral pneumonia with evidence of combined T- and B-cell immunodeficiency. Whole exome sequencing revealed biallelic missense mutations in the NSMCE3 gene encoding a subunit of the SMC5/6 complex, essential for DNA damage response and chromosome segregation. The NSMCE3 mutations disrupt interactions within the SMC5/6 complex, leading to destabilization of the complex. Patient cells showed chromosome rearrangements, micronuclei, sensitivity to replication stress and DNA damage, and defective homologous recombination.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001787","title":"Integrative genomic and functional analysis reveals roles of CASP8 and FAT1 in oral squamous cell carcinoma","description":"Oral squamous cell carcinoma (OSCC) is genetically highly heterogeneous, contributing to the challenges of treatment. To create an in vitro model that mimics this heterogeneity, we generated a panel of HPV-negative OSCC cell lines. By whole exome sequencing of the lines and matched patient blood samples, we demonstrate that the mutational spectrum of the lines is representative of primary OSCC in The Cancer Genome Atlas. We show that loss of function mutations in FAT1 (an atypical cadherin) and CASP8 (Caspase 8) frequently occur in the same tumour. OSCC cells with inactivating FAT1 mutations exhibited reduced intercellular adhesion. Knockdown of FAT1 and CASP8 individually or in combination in OSCC cells led to increased cell migration and clonal growth, resistance to Staurosporine-induced apoptosis and, in some cases, increased terminal differentiation. The OSCC lines represent a valuable resource for elucidating the impact of different mutations on tumour behaviour.","abstract":"Oral squamous cell carcinoma (OSCC) is genetically highly heterogeneous, contributing to the challenges of treatment. To create an in vitro model that mimics this heterogeneity, we generated a panel of HPV-negative OSCC cell lines. By whole exome sequencing of the lines and matched patient blood samples, we demonstrate that the mutational spectrum of the lines is representative of primary OSCC in The Cancer Genome Atlas. We show that loss of function mutations in FAT1 (an atypical cadherin) and CASP8 (Caspase 8) frequently occur in the same tumour. OSCC cells with inactivating FAT1 mutations exhibited reduced intercellular adhesion. Knockdown of FAT1 and CASP8 individually or in combination in OSCC cells led to increased cell migration and clonal growth, resistance to Staurosporine-induced apoptosis and, in some cases, increased terminal differentiation. The OSCC lines represent a valuable resource for elucidating the impact of different mutations on tumour behaviour.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001788","title":"Genomic Profiling of Thyroid Cancer Reveals a Role for Thyroglobulin in Metastasis","description":"Papillary thyroid carcinoma (PTC) has a wide geographic variation in incidence, being highest in Saudi Arabia where it is only second to breast cancer as the most common cancer among females.  Genomic profiling of PTC from Saudi Arabia has not been attempted previously.  We performed whole-exome sequencing of 101 PTC samples and the corresponding genomic DNA to identify genes with recurrent somatic mutations, followed by sequencing of these genes using a next-generation gene panel approach in further 785 samples.  In addition to BRAF, N-RAS and H-RAS, which have previously been shown to be recurrently mutated in PTC, our analysis highlights additional genes, including thyroglobulin (TG), which harbored somatic mutations in 3% of the entire cohort.  Surprisingly, although TG mutations were not exclusive to mutations in the RAS-MAP kinase pathway, their presence was associated with a significantly worse clinical outcome, which suggests a pathogenic role beyond driving initial oncogenesis.  Analysis of metastatic PTC tissue revealed significant enrichment for TG mutations (p&lt;0.001), including events of apparent clonal expansion.  Our results suggest a previously unknown role of TG somatic mutations in the pathogenesis of PTC and its malignant evolution.","abstract":"Papillary thyroid carcinoma (PTC) has a wide geographic variation in incidence, being highest in Saudi Arabia where it is only second to breast cancer as the most common cancer among females.  Genomic profiling of PTC from Saudi Arabia has not been attempted previously.  We performed whole-exome sequencing of 101 PTC samples and the corresponding genomic DNA to identify genes with recurrent somatic mutations, followed by sequencing of these genes using a next-generation gene panel approach in further 785 samples.  In addition to BRAF, N-RAS and H-RAS, which have previously been shown to be recurrently mutated in PTC, our analysis highlights additional genes, including thyroglobulin (TG), which harbored somatic mutations in 3% of the entire cohort.  Surprisingly, although TG mutations were not exclusive to mutations in the RAS-MAP kinase pathway, their presence was associated with a significantly worse clinical outcome, which suggests a pathogenic role beyond driving initial oncogenesis.  Analysis of metastatic PTC tissue revealed significant enrichment for TG mutations (p&lt;0.001), including events of apparent clonal expansion.  Our results suggest a previously unknown role of TG somatic mutations in the pathogenesis of PTC and its malignant evolution.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-04-24T11:13:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001789","title":"Rare disruptive mutations in ciliary function genes contribute to testicular cancer susceptibility","description":"Testicular germ cell tumor (TGCT) is the most common cancer in young men1,2. Here we aimed to identify novel risk factors for TGCT using whole-exome sequencing, which was performed on 328 affected individuals from 153 families, 634 sporadic cases and 1,644 controls. We searched for genes that were recurrently affected by rare variants (minor allele frequency &lt;0.01) with potentially damaging effects and evidence of segregation in families. 8.7% of families carried rare disruptive mutations in the cilia-microtubule genes (CMG) as compared to 0.5% of controls3 (P=2.1x10-8). The most significantly mutated CMG was DNAAF1 with biallelic inactivation and loss of DNAAF1 expression shown in tumors from carriers. DNAAF1 as a cause of TGCT was supported by a DNAAF1Hu255h(+/-) zebrafish model with 94% penetrance for TGCT compared to 14% in wildtype fish. These data implicate cilia-microtubule inactivation as a cause of TGCT development and are the first evidence for CMGs as cancer susceptibility genes.","abstract":"Testicular germ cell tumor (TGCT) is the most common cancer in young men1,2. Here we aimed to identify novel risk factors for TGCT using whole-exome sequencing, which was performed on 328 affected individuals from 153 families, 634 sporadic cases and 1,644 controls. We searched for genes that were recurrently affected by rare variants (minor allele frequency &lt;0.01) with potentially damaging effects and evidence of segregation in families. 8.7% of families carried rare disruptive mutations in the cilia-microtubule genes (CMG) as compared to 0.5% of controls3 (P=2.1x10-8). The most significantly mutated CMG was DNAAF1 with biallelic inactivation and loss of DNAAF1 expression shown in tumors from carriers. DNAAF1 as a cause of TGCT was supported by a DNAAF1Hu255h(+/-) zebrafish model with 94% penetrance for TGCT compared to 14% in wildtype fish. These data implicate cilia-microtubule inactivation as a cause of TGCT development and are the first evidence for CMGs as cancer susceptibility genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-04-25T18:06:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001790","title":"Zhong Shan Hospital liver tumor single cell sequencing:111 single cell and 7 tissues.","description":"Zhong Shan Hospital liver tumor single cell sequencing:111 single cell and 7 tissues.","abstract":"Zhong Shan Hospital liver tumor single cell sequencing:111 single cell and 7 tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001791","title":"ZhongShan Hospital liver tumor single cell sequencing.","description":"ZhongShan Hospital liver tumor single cell sequencing.","abstract":"ZhongShan Hospital liver tumor single cell sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-04-27T04:46:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001792","title":"PGP_UK_samples_for_demographic_analysis","description":"PGP is an initiative started in the USA to create a cohort of human subjects fully consented for completely open data research use. Recently a UK arm of the project was launched: PGP-UK &lt;http://www.personalgenomes.org/uk&gt; and over 1,000 people have fully enrolled and consented, with many more completing preliminary registration. In this study we obtained ~30x coverage whole genome sequence data for a number of PGP-UK participants.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"PGP is an initiative to create a cohort of human subjects fully consented for completely open data research use.  In November 2013 a UK arm, PGP-UK, launched &lt;http://www.personalgenomes.org/uk&gt;.  This study contains whole genome sequences of PGP-UK samples, made freely available under broad consent for scientific research (see PGP-UK web site for details).","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001793","title":"Whole_Genome_Sequencing_of_Kenyan__severe_malaria_cases","description":"This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/.  Further specific information regarding the release of MalariaGEN datasets can be found at https://www.malariagen.net/node/54","abstract":"500 Severe Malaria Cases from Kenya will be sequenced to at least x30 coverage.  Human and, if possible, Plasmodium falciparum polymorphisms will be called.   This study forms part of the MalariaGEN Consortial Project 1, a project to investigate genetic determinants of resistance to malaria.  We will also investigate the parasite population in these cases and begin to look at genome interactions between both parasite and human.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001794","title":"Single_cell_methylation_profiling","description":"Single-cell methylome and transcriptome mapping in pre-implantation embryos. Libraries produced using scM&amp;T-seq (Angermueller et al, Nature Methods 2016) \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Map single-cell methylation profiles in pre-implantation human embryos. Explore relationships between gene expression and DNA methylation by use of parrallel single-cell sequencing.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001795","title":"RNA-sequencing data from 195 B-cell precursor acute lymphoblastic leukemias and mate pair whole genome sequencing data from 15 B-cell precursor acute lymphoblastic leukemias","description":"Fusion genes are potent driver mutations in cancer. In this study, we delineate the fusion gene landscape in a consecutive series of 195 pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL). Using RNA-sequencing, we find in-frame fusion genes in 127 (65%) cases, including 27 novel fusions. We describe a new subtype characterized by recurrent IGH-DUX4 or ERG-DUX4 fusions, representing 4% of cases, leading to overexpression of DUX4 and frequently co-occurring with intragenic ERG deletions. Furthermore, we identify a subtype characterized by an ETV6-RUNX1-like gene expression profile and coexisting ETV6 and IKZF1 alterations. Taken together, this study provides a detailed overview of fusion genes in pediatric BCP ALL and adds new pathogenetic insights, which may improve risk stratification and provide novel therapeutic options in this disease.","abstract":"Fusion genes are potent driver mutations in cancer. In this study, we delineate the fusion gene landscape in a consecutive series of 195 pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL). Using RNA-sequencing, we find in-frame fusion genes in 127 (65%) cases, including 27 novel fusions. We describe a new subtype characterized by recurrent IGH-DUX4 or ERG-DUX4 fusions, representing 4% of cases, leading to overexpression of DUX4 and frequently co-occurring with intragenic ERG deletions. Furthermore, we identify a subtype characterized by an ETV6-RUNX1-like gene expression profile and coexisting ETV6 and IKZF1 alterations. Taken together, this study provides a detailed overview of fusion genes in pediatric BCP ALL and adds new pathogenetic insights, which may improve risk stratification and provide novel therapeutic options in this disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-04-27T20:05:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001796","title":"VELOUR","description":"Colorectal cancer samples from clinical trial of chemotherapy +/- Aflibercept","abstract":"A colorectal cancer-specific targeted gene screen of FFPE samples from approx. 600 colorectal cancer samples from clinical trial of chemotherapy +/- Aflibercept. Goal is to identify molecular features that correlate with treatment response and resistance.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001797","title":"Targeted_gene_screen_of_drug_resistant_organoids","description":"Sequencing of drug resistant organoids","abstract":"Sequencing of drug resistant organoids","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-04-29T09:18:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001798","title":"Cancer_Cell_Line_Genotyping","description":"Cell lines being used as model systems to elucidate mechanisms of drug response require genotyping to confirm their identity.","abstract":"Cell lines being used as model systems to elucidate mechanisms of drug response require genotyping to confirm their identity.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001799","title":"Spiradenocarcinoma","description":"•\tSpiradenocarcinoma is a rare cutaneous sweat gland adnexal cancer with potential for aggressive behaviour. They are classified histologically into low- and high-grade tumours, with morphologically low-grade tumours thought to behave more favourably. However, limited information is available, with only 18 published cases.\n•\tWe have collected morphologically low-grade spiroadenocarcinomas (one with a lung metastasis) and high-grade spiroadenocarcinomas, as well as some spiradenomas (benign lesions),  cylindromas (another type of malignant cutaneous sweat gland adnexal tumour) and hybrid spiradenoma-cylindromas.\n•\tH&amp;E-stained sections were reviewed, follow-up was obtained, and immunohistochemistry for Ki-67, p53 and, MYB has been performed. The tumours were solitary, measuring 0.8-7?cm (median: 2.7?cm), with a predilection for the head and neck of elderly patients (median age: 72 years; range 53-92) without gender bias. Histologically, the tumours were multinodular and located in deep dermis and subcutis. A pre-existing spiradenoma was present in all cases. The malignant component was characterized by expansile growth with loss of the dual cell population, up to moderate cytological atypia and increased mitotic activity (median: 10/10 HPF; range 1-28). Additional findings included squamoid differentiation (n=9), necrosis (n=7), and ulceration (n=5). P53 expression was variable and no significant differences were noted in the benign compared with the malignant parts of the tumours. In contrast, in the malignant components the Ki-67 proliferative index was slightly increased, and MYB expression was lost. Follow-up (median: 67 months; range: 13-132) available for 16 patients (84%) revealed a local recurrence rate of 19% but no metastases or disease-related mortality.\n•\tHere we wish to exome sequence these cases to define the first genomic landscape for this malignancy.","abstract":"•\tSpiradenocarcinoma is a rare cutaneous sweat gland adnexal cancer with potential for aggressive behaviour. They are classified histologically into low- and high-grade tumours, with morphologically low-grade tumours thought to behave more favourably. However, limited information is available, with only 18 published cases.\n•\tWe have collected morphologically low-grade spiroadenocarcinomas (one with a lung metastasis) and high-grade spiroadenocarcinomas, as well as some spiradenomas (benign lesions),  cylindromas (another type of malignant cutaneous sweat gland adnexal tumour) and hybrid spiradenoma-cylindromas.\n•\tH&amp;E-stained sections were reviewed, follow-up was obtained, and immunohistochemistry for Ki-67, p53 and, MYB has been performed. The tumours were solitary, measuring 0.8-7?cm (median: 2.7?cm), with a predilection for the head and neck of elderly patients (median age: 72 years; range 53-92) without gender bias. Histologically, the tumours were multinodular and located in deep dermis and subcutis. A pre-existing spiradenoma was present in all cases. The malignant component was characterized by expansile growth with loss of the dual cell population, up to moderate cytological atypia and increased mitotic activity (median: 10/10 HPF; range 1-28). Additional findings included squamoid differentiation (n=9), necrosis (n=7), and ulceration (n=5). P53 expression was variable and no significant differences were noted in the benign compared with the malignant parts of the tumours. In contrast, in the malignant components the Ki-67 proliferative index was slightly increased, and MYB expression was lost. Follow-up (median: 67 months; range: 13-132) available for 16 patients (84%) revealed a local recurrence rate of 19% but no metastases or disease-related mortality.\n•\tHere we wish to exome sequence these cases to define the first genomic landscape for this malignancy.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-04-29T11:21:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001800","title":"Spatio-temporal evolution of the primary glioblastoma genome (newly added after 2015)","description":"Since our genomic analysis of 38 GBM patients, we recruited more cases to further study spatial and temporal evolution of glioblastoma with international collaboration of multiple institutes. The cases in this study includes the whole exome and transcriptome of GBM patients newly recruited in Samsung Medical Center.","abstract":"Since our genomic analysis of 38 GBM patients, we recruited more cases to further study spatial and temporal evolution of glioblastoma with international collaboration of multiple institutes. The cases in this study includes the whole exome and transcriptome of GBM patients newly recruited in Samsung Medical Center.","study_type":"Other","pubmed_ids":[27270107],"external_links":null,"is_released":true,"released_date":"2016-05-01T04:18:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001801","title":"Comparing nodal versus bony metastatic spread using tumour phylogenies","description":"The role of lymph node metastases in distant prostate cancer dissemination and lethality is ill defined. Patients with metastases restricted to lymph nodes have a better prognosis than those with distant metastatic spread, suggesting the possibility of distinct aetiologies. To explore this, we traced patterns of cancer dissemination using tumour phylogenies inferred from genome-wide copy-number profiling of 48 samples across 3 patients with lymph node metastatic disease and 3 patients with osseous metastatic disease. Our results show that metastatic cells in regional lymph nodes originate from evolutionary advanced extra-prostatic tumour cells rather than less advanced central tumour cell populations. In contrast, osseous metastases do not exhibit such a constrained developmental lineage, arising from either intra or extra-prostatic tumour cell populations, at early and late stages in the evolution of the primary. Collectively, this comparison suggests that lymph node metastases may not be an intermediate developmental step for distant osseous metastases, but rather represent a distinct metastatic lineage.","abstract":"The role of lymph node metastases in distant prostate cancer dissemination and lethality is ill defined. Patients with metastases restricted to lymph nodes have a better prognosis than those with distant metastatic spread, suggesting the possibility of distinct aetiologies. To explore this, we traced patterns of cancer dissemination using tumour phylogenies inferred from genome-wide copy-number profiling of 48 samples across 3 patients with lymph node metastatic disease and 3 patients with osseous metastatic disease. Our results show that metastatic cells in regional lymph nodes originate from evolutionary advanced extra-prostatic tumour cells rather than less advanced central tumour cell populations. In contrast, osseous metastases do not exhibit such a constrained developmental lineage, arising from either intra or extra-prostatic tumour cell populations, at early and late stages in the evolution of the primary. Collectively, this comparison suggests that lymph node metastases may not be an intermediate developmental step for distant osseous metastases, but rather represent a distinct metastatic lineage.","study_type":"Other","pubmed_ids":[27653089],"external_links":null,"is_released":true,"released_date":"2016-05-04T04:11:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001802","title":"Native_American_Ancient_DNA_sequencing","description":"The morphology of the first humans in the Americas (Paleoamericans) differs from that of Native Americans, and has raised the question of whether or not there are also differences in origin or genetics. A few populations who survived until relatively recently have been suggested to retain Paleoamerican morphology. One of these populations is from La Jolla. Here, we have generated genome sequence data from four La Jolla individuals in order to investigate these questions\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The morphology of the first humans in the Americas (Paleoamericans) differs from that of Native Americans, and has raised the question of whether or not there are also differences in origin or genetics. A few populations who survived until relatively recently have been suggested to retain Paleoamerican morphology. One of these populations is from La Jolla. Here, we have generated genome sequence data from four La Jolla individuals in order to investigate these questions.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-05T11:28:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001803","title":"Characterization of a human iPSC-derived endocrine pancreas model","description":"Directed differentiation of stem cells offers a scalable solution to the need for human cell models recapitulating islet biology and T2D pathogenesis. We profiled mRNA expression at six stages of an induced pluripotent stem cell (iPSC) model of endocrine pancreas development from two donors, and characterized the distinct transcriptomic profiles associated with each stage. Established regulators of endodermal lineage commitment, such as SOX17 (log2 fold change [FC] compared to iPSCs=14.2, p-value=4.9x10-5) and the pancreatic agenesis gene GATA6 (log2 FC=12.1, p-value=8.6x10-5), showed transcriptional variation consistent with their known developmental roles. However, these analyses highlighted many other genes with stage-specific expression patterns, some of which may be novel drivers or markers of islet development. For example, the leptin receptor gene, LEPR, was most highly expressed in published data from in vivo-matured cells compared to our endocrine pancreas-like cells (log2 FC=5.5, p-value=2.0x10-12), suggesting a role for the leptin pathway in the maturation process. Endocrine pancreas-like cells showed significant stage-selective expression of adult islet genes, including INS, ABCC8, and GLP1R, and enrichment of relevant GO-terms (e.g. \"insulin secretion\"; odds ratio=4.2, p-value=1.9x10-3): however, principal component analysis indicated that in vitro-differentiated cells were more immature than adult islets. Integration of the stage-specific expression information with genetic data from T2D genome-wide association studies revealed that 46 of 82 T2D-associated loci harbor genes present in at least one developmental stage, facilitating refinement of potential effector transcripts. Together, these data show that expression profiling in an iPSC islet development model can further understanding of islet biology and T2D pathogenesis.","abstract":"Directed differentiation of stem cells offers a scalable solution to the need for human cell models recapitulating islet biology and T2D pathogenesis. We profiled mRNA expression at six stages of an induced pluripotent stem cell (iPSC) model of endocrine pancreas development from two donors, and characterized the distinct transcriptomic profiles associated with each stage. Established regulators of endodermal lineage commitment, such as SOX17 (log2 fold change [FC] compared to iPSCs=14.2, p-value=4.9x10-5) and the pancreatic agenesis gene GATA6 (log2 FC=12.1, p-value=8.6x10-5), showed transcriptional variation consistent with their known developmental roles. However, these analyses highlighted many other genes with stage-specific expression patterns, some of which may be novel drivers or markers of islet development. For example, the leptin receptor gene, LEPR, was most highly expressed in published data from in vivo-matured cells compared to our endocrine pancreas-like cells (log2 FC=5.5, p-value=2.0x10-12), suggesting a role for the leptin pathway in the maturation process. Endocrine pancreas-like cells showed significant stage-selective expression of adult islet genes, including INS, ABCC8, and GLP1R, and enrichment of relevant GO-terms (e.g. \"insulin secretion\"; odds ratio=4.2, p-value=1.9x10-3): however, principal component analysis indicated that in vitro-differentiated cells were more immature than adult islets. Integration of the stage-specific expression information with genetic data from T2D genome-wide association studies revealed that 46 of 82 T2D-associated loci harbor genes present in at least one developmental stage, facilitating refinement of potential effector transcripts. Together, these data show that expression profiling in an iPSC islet development model can further understanding of islet biology and T2D pathogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-05T12:11:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001804","title":"Interactions between the tumor and the systemic response of breast cancer patients","description":"Breast cancer (BC) research has largely focused on the molecular properties of the tumor proper. However, to understand how cancer progresses and ultimately modulates patient outcome, we also require an understanding of the molecular changes in the patient systemic response (SR). Toward this end, we generated and analyzed RNA profiles from tumor and matched blood samples in 173 BC patients. We designed a system (MIxT) to explore and link tightly co-expressed gene sets (modules) across matched tissues. The gene composition of modules, and their expression, largely vary across tissues. Distinct patterns of expression in the SR are predominantly detected in highly immunogenic BC subtypes. We also find that the expression pattern of a module in one tissue is correlated to the expression pattern of a module in the other tissue in a fashion that depends on subtype. For example, systemic immunosuppression is detected in basalL patients in a fashion that is proportional to the level of expression of several tumor modules highlighting immune evasion mechanisms active in these particular cancers.","abstract":"Breast cancer (BC) research has largely focused on the molecular properties of the tumor proper. However, to understand how cancer progresses and ultimately modulates patient outcome, we also require an understanding of the molecular changes in the patient systemic response (SR). Toward this end, we generated and analyzed RNA profiles from tumor and matched blood samples in 173 BC patients. We designed a system (MIxT) to explore and link tightly co-expressed gene sets (modules) across matched tissues. The gene composition of modules, and their expression, largely vary across tissues. Distinct patterns of expression in the SR are predominantly detected in highly immunogenic BC subtypes. We also find that the expression pattern of a module in one tissue is correlated to the expression pattern of a module in the other tissue in a fashion that depends on subtype. For example, systemic immunosuppression is detected in basalL patients in a fashion that is proportional to the level of expression of several tumor modules highlighting immune evasion mechanisms active in these particular cancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-06T21:30:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001805","title":"A novel TP53-KPNA3 translocation defines a de novo treatment-resistant clone in osteosarcoma","description":"Osteosarcoma is the most common primary bone cancer.  It can be cured by aggressive surgery and chemotherapy, but outcomes for metastatic or chemoresistant disease remain dismal.  Cancer sequencing studies have shown that the p53 pathway is dysregulated in nearly every case, often by translocation; however, no studies of osteosarcoma evolution or intratumor heterogeneity have been done to date.  We studied a patient with chemoresistant, metastatic disease over the course of three years.  We performed exome sequencing on germline DNA and DNA collected from tumor at three separate timepoints.  We compared variant calls and variant allele frequencies between different samples.  We identified subclonal driver mutations in several different genes in the primary tumor sample and found that one particular subclone dominated subsequent tumor samples at relapse.  This clone was marked by a novel TP53-KPNA3 translocation and loss of the opposite-strand wild-type TP53 allele.  Future research must focus on functional significance of such clones and strategies to eliminate them.","abstract":"Osteosarcoma is the most common primary bone cancer.  It can be cured by aggressive surgery and chemotherapy, but outcomes for metastatic or chemoresistant disease remain dismal.  Cancer sequencing studies have shown that the p53 pathway is dysregulated in nearly every case, often by translocation; however, no studies of osteosarcoma evolution or intratumor heterogeneity have been done to date.  We studied a patient with chemoresistant, metastatic disease over the course of three years.  We performed exome sequencing on germline DNA and DNA collected from tumor at three separate timepoints.  We compared variant calls and variant allele frequencies between different samples.  We identified subclonal driver mutations in several different genes in the primary tumor sample and found that one particular subclone dominated subsequent tumor samples at relapse.  This clone was marked by a novel TP53-KPNA3 translocation and loss of the opposite-strand wild-type TP53 allele.  Future research must focus on functional significance of such clones and strategies to eliminate them.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-09T18:25:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001806","title":"V2_Colorectal_panel_test","description":"Targeted gene screen of cell line tumour samples for testing the new V2 Colorectal gene panel.","abstract":"Targeted gene screen of cell line tumour samples for testing the new V2 Colorectal gene panel.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-10T11:00:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001807","title":"V4_Colorectal_panel_test","description":"Targeted gene screen of cell line tumours for testing the new V4 Colorectal gene panel.","abstract":"Targeted gene screen of cell line tumours for testing the new V4 Colorectal gene panel.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-10T11:00:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001808","title":"V4_panel_bait_design_test","description":"Targeted gene screen of FFPEs, cell lines and primary tumours for testing the new V4 Cancer gene panel.","abstract":"Targeted gene screen of FFPEs, cell lines and primary tumours for testing the new V4 Cancer gene panel.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-10T11:00:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001809","title":"Testing study created in Webin","description":"Testing study created in Webin","abstract":"Testing study created in Webin","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001810","title":"Clonal selection and double hit events involving tumor suppressor genes underlie relapse from total therapy","description":"In order to gain insights into the mechanisms of disease progression in multiple myeloma (MM) patients treated with multi-agent and high-dose chemotherapy we have performed a longitudinal study of 33 patients entered into Total Therapy protocols using gene expression profiling, high resolution copy number analyses and whole exome sequencing. The results of this study show the importance of acquired mutations in MM driver genes, bi-allelic events affecting tumor suppressor genes and increased proliferation rates in driving relapse, which is enhanced by intra-clonal heterogeneity and Darwinian type clonal evolution. Branching was the most frequent evolution pattern, characterized by clonal loss and appearance of new clones. We found a higher number of lost and acquired copy number aberrations and an excess of bi-allelic inactivation of tumor suppressor genes in GEP70 high risk (HiR) cases, consistent with genomic instability being a key feature of HiR MM. In conclusion, our study further stresses the impact of known prognostic markers and driver genes on the fitness level of MM cells to survive multi-agent chemotherapy. The frequent bi-allelic loss of tumor suppressor genes in HiR cases and the potentially resulting failure of treatment with DNA damaging agents highlight the need for new therapies for HiR MM.","abstract":"In order to gain insights into the mechanisms of disease progression in multiple myeloma (MM) patients treated with multi-agent and high-dose chemotherapy we have performed a longitudinal study of 33 patients entered into Total Therapy protocols using gene expression profiling, high resolution copy number analyses and whole exome sequencing. The results of this study show the importance of acquired mutations in MM driver genes, bi-allelic events affecting tumor suppressor genes and increased proliferation rates in driving relapse, which is enhanced by intra-clonal heterogeneity and Darwinian type clonal evolution. Branching was the most frequent evolution pattern, characterized by clonal loss and appearance of new clones. We found a higher number of lost and acquired copy number aberrations and an excess of bi-allelic inactivation of tumor suppressor genes in GEP70 high risk (HiR) cases, consistent with genomic instability being a key feature of HiR MM. In conclusion, our study further stresses the impact of known prognostic markers and driver genes on the fitness level of MM cells to survive multi-agent chemotherapy. The frequent bi-allelic loss of tumor suppressor genes in HiR cases and the potentially resulting failure of treatment with DNA damaging agents highlight the need for new therapies for HiR MM.","study_type":"Other","pubmed_ids":[27516441],"external_links":null,"is_released":true,"released_date":"2016-05-10T20:25:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001811","title":"Genome_Diversity_in_Africa_Project__Gambia","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region.\nThe Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).\nOur scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001812","title":"Genome_Diversity_in_Africa_Project__Maasai","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region.\nThe Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).\nOur scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001821","title":"Epigenome and transcriptome profiling of chronic lymphocytic leukemia patients","description":"Chronic lymphocytic leukemia (CLL) is characterized by substantial clinical heterogeneity, despite relatively few genetic alterations. To provide a basis for studying epigenome deregulation in CLL, we established genome-wide chromatin accessibility maps for 88 CLL samples from 55 patients using the ATAC-seq assay, and we also performed ChIPmentation and RNA-seq profiling for ten representative samples. Based on the resulting dataset, we devised and applied a bioinformatic method that links chromatin profiles to clinical annotations. Our analysis identified sample-specific variation on top of a shared core of CLL regulatory regions. IGHV mutation status – which distinguishes the two major subtypes of CLL – was accurately predicted by the chromatin profiles, and gene regulatory networks inferred for IGHV-mutated vs. IGHV-unmutated samples identified characteristic differences between these two disease subtypes. In summary, we discovered widespread heterogeneity in the chromatin landscape of CLL, established a community resource for studying epigenome deregulation in leukemia, and demonstrated the feasibility of chromatin accessibility mapping in cancer cohorts and clinical research.","abstract":"Chronic lymphocytic leukemia (CLL) is characterized by substantial clinical heterogeneity, despite relatively few genetic alterations. To provide a basis for studying epigenome deregulation in CLL, we established genome-wide chromatin accessibility maps for 88 CLL samples from 55 patients using the ATAC-seq assay, and we also performed ChIPmentation and RNA-seq profiling for ten representative samples. Based on the resulting dataset, we devised and applied a bioinformatic method that links chromatin profiles to clinical annotations. Our analysis identified sample-specific variation on top of a shared core of CLL regulatory regions. IGHV mutation status – which distinguishes the two major subtypes of CLL – was accurately predicted by the chromatin profiles, and gene regulatory networks inferred for IGHV-mutated vs. IGHV-unmutated samples identified characteristic differences between these two disease subtypes. In summary, we discovered widespread heterogeneity in the chromatin landscape of CLL, established a community resource for studying epigenome deregulation in leukemia, and demonstrated the feasibility of chromatin accessibility mapping in cancer cohorts and clinical research.","study_type":"Other","pubmed_ids":[27346425],"external_links":null,"is_released":true,"released_date":"2016-05-11T20:08:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001822","title":"QSEA – modelling of genome-wide DNA methylation from sequencing enrichment experiments","description":"We describe a new method, QSEA, for analyzing methylation enrichment data. We generated a benchmark experiment consisting of MeDIP-seq enrichment data, targeted BS-seq validation data, and RNA-seq data on five pairs of tumor and adjacent normal samples of non-small cell lung cancer patients.\n\nDetails of the method and its performance on the data have been described in Lienhard et al. (2016).","abstract":"We describe a new method, QSEA, for analyzing methylation enrichment data. We generated a benchmark experiment consisting of MeDIP-seq enrichment data, targeted BS-seq validation data, and RNA-seq data on five pairs of tumor and adjacent normal samples of non-small cell lung cancer patients.\n\nDetails of the method and its performance on the data have been described in Lienhard et al. (2016).","study_type":"Other","pubmed_ids":[27913729],"external_links":null,"is_released":true,"released_date":"2016-05-12T08:47:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001825","title":"Institut Curie - CNG Neuroblastoma Whole Genome Sequencing Diagnosis Relapse","description":"Neuroblastoma, a clinically heterogeneous pediatric cancer, is characterized by distinct genomic profiles but few recurrent mutations. As neuroblastoma is expected to have high degree of genetic heterogeneity, study of neuroblastoma's clonal evolution with deep coverage whole-genome sequencing of diagnosis and relapse samples will lead to a better understanding of the molecular events associated with relapse.  Samples were included in this study if sufficient DNA from constitutional, diagnosis and relapse tumors was available for WGS.  Whole genome sequencing was performed on trios (constitutional, diagnose and relapse DNA).","abstract":"Neuroblastoma, a clinically heterogeneous pediatric cancer, is characterized by distinct genomic profiles but few recurrent mutations. As neuroblastoma is expected to have high degree of genetic heterogeneity, study of neuroblastoma's clonal evolution with deep coverage whole-genome sequencing of diagnosis and relapse samples will lead to a better understanding of the molecular events associated with relapse.  Samples were included in this study if sufficient DNA from constitutional, diagnosis and relapse tumors was available for WGS.  Whole genome sequencing was performed on trios (constitutional, diagnose and relapse DNA).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001828","title":"Genome_Diversity_in_Africa_Project___GemCode_libraries_","description":"High depth whole genome sequencing  from GemCode (10x Genomics) DNA libraries containing long range linkage information for one Baganda trio and one Baganda child (parent already sequenced at high depth).\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Given the central importance of Africa to studies of human origins, genetic diversity and disease susceptibility, large-scale and representative characterisation of genetic diversity in Africa is needed. One of the biggest challenges in reconstructing genomes from short read data is the limited phasing information. The use of DNA libraries containing long range linkage information could present a significant advantage. These high coverage data for 1 Baganda (Uganda) trio with extensive pedigree data and already sequenced relatives and 1 Baganda child, whose parents have been already sequenced at high depth, have been generated from GemCode (10x Genomics) DNA libraries containing long range linkage information.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-13T13:00:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001829","title":"Esophagus cancer project hold by Esophageal laboratory of first affiliated hospital of zhengzhou university.","description":"Whole-genome sequencing in 60 cases and whole-exome sequencing in 146 cases of Chinese ESCC","abstract":"Whole-genome sequencing in 60 cases and whole-exome sequencing in 146 cases of Chinese ESCC","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001833","title":"METABRIC: Data from Pereira et al (2016), The somatic mutation profiles of 2433 breast cancers refine their genomic and transcriptomic landscapes. Nat Comms 7.","description":"NOTE THAT THESE SAMPLES ARE THE ONES REFERENCED IN PEREIRA ET AL (2016) AND LINKED IN EGAS00001001753.\n \nThe genomic landscape of breast cancer is complex, and inter- and intra-tumour heterogeneity are important challenges in treating the disease.  In this study, we sequence 173 genes in 2433 primary breast tumours that have copy number aberration (CNA), gene expression, and long-term clinical follow-up data.  We identify 40 mutation-driver (Mut-driver) genes, and determine associations between mutations, driver CNA profiles, clinical-pathological parameters, and survival.  We assess the clonal states of Mut-driver mutations, and estimate levels of intratumour heterogeneity using mutant allele fractions.   Associations between PIK3CA mutations and reduced survival are identified in three subgroups of ER-positive cancer (defined by amplification of 17q23, 11q13-14 or 8q24).  High levels of intratumour heterogeneity are in general associated with worse outcome, but highly aggressive tumours with 11q13-14 amplification have low levels of intratumour heterogeneity.  These results emphasise the importance of genome-based stratification of breast cancer, and have important implications for designing therapeutic strategies.","abstract":"NOTE THAT THESE SAMPLES ARE THE ONES REFERENCED IN PEREIRA ET AL (2016) AND LINKED IN EGAS00001001753.\n \nThe genomic landscape of breast cancer is complex, and inter- and intra-tumour heterogeneity are important challenges in treating the disease.  In this study, we sequence 173 genes in 2433 primary breast tumours that have copy number aberration (CNA), gene expression, and long-term clinical follow-up data.  We identify 40 mutation-driver (Mut-driver) genes, and determine associations between mutations, driver CNA profiles, clinical-pathological parameters, and survival.  We assess the clonal states of Mut-driver mutations, and estimate levels of intratumour heterogeneity using mutant allele fractions.   Associations between PIK3CA mutations and reduced survival are identified in three subgroups of ER-positive cancer (defined by amplification of 17q23, 11q13-14 or 8q24).  High levels of intratumour heterogeneity are in general associated with worse outcome, but highly aggressive tumours with 11q13-14 amplification have low levels of intratumour heterogeneity.  These results emphasise the importance of genome-based stratification of breast cancer, and have important implications for designing therapeutic strategies.","study_type":"Other","pubmed_ids":[27161491],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001835","title":"Whole exome sequencing of Finnish hereditary breast cancer families","description":"A remarkable proportion of factors causing genetic predisposition to breast cancer (BC) are unknown in non-BRCA1/2 families. Exome sequencing was performed for 13 high-risk Finnish hereditary breast and/or ovarian cancer (HBOC) families to detect variants contributing to BC susceptibility","abstract":"A remarkable proportion of factors causing genetic predisposition to breast cancer (BC) are unknown in non-BRCA1/2 families. Exome sequencing was performed for 13 high-risk Finnish hereditary breast and/or ovarian cancer (HBOC) families to detect variants contributing to BC susceptibility","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-16T19:02:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001836","title":"Identification of 19 novel loci reveals gene regulatory mechanisms determining susceptibility to testicular germ cell tumour","description":"Testicular germ cell tumour (TGCT) is the most common cancer in young men1,2, and is characterised by strong inherited genetic risk factors3. Here we have undertaken large-scale genome wide association study (GWAS) for TGCT, encompassing ~7,500 cases and ~23,000 controls, through the Oncoarray consortium. We identified 19 novel loci, approximately doubling the number of known TGCT risk loci to 44 (P&lt;5x10-8)4-14 and conduct deep, high-throughput functional annotation of all risk loci. We establish a network of physical interactions for all risk SNPs to candidate casual genes in 3D space, using high-throughput chromosome conformation capture techniques (HiC) in TGCT cells. Firstly, functional evidence reveals widespread disruption of developmental transcriptional regulators, consistent with failed primordial germ cell differentiation as an initiating step in TGCT oncogenesis15. We secondly observe multiple risk loci associated with defective microtubule assembly, compatible with the high level of aneuploidy observed in TGCTs, suggesting gross chromosomal instability. Finally KIT-MAPK signalling features as a recurrently dysregulated pathway. In summary our findings substantially increase the number of known TGCT risk alleles, and provides a functional basis for disease susceptibility.","abstract":"Testicular germ cell tumour (TGCT) is the most common cancer in young men1,2, and is characterised by strong inherited genetic risk factors3. Here we have undertaken large-scale genome wide association study (GWAS) for TGCT, encompassing ~7,500 cases and ~23,000 controls, through the Oncoarray consortium. We identified 19 novel loci, approximately doubling the number of known TGCT risk loci to 44 (P&lt;5x10-8)4-14 and conduct deep, high-throughput functional annotation of all risk loci. We establish a network of physical interactions for all risk SNPs to candidate casual genes in 3D space, using high-throughput chromosome conformation capture techniques (HiC) in TGCT cells. Firstly, functional evidence reveals widespread disruption of developmental transcriptional regulators, consistent with failed primordial germ cell differentiation as an initiating step in TGCT oncogenesis15. We secondly observe multiple risk loci associated with defective microtubule assembly, compatible with the high level of aneuploidy observed in TGCTs, suggesting gross chromosomal instability. Finally KIT-MAPK signalling features as a recurrently dysregulated pathway. In summary our findings substantially increase the number of known TGCT risk alleles, and provides a functional basis for disease susceptibility.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-17T13:51:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001837","title":"Dense_fine_mapping_study_identifies_new_susceptibility_loci_for_primary_biliary_cirrhosis","description":"2,981 primary biliary cirrhosis (PBC) cases were collected by the UK PBC Consortium and genotyped on the Illumina Immunochip where 2,861 passed quality control. These cases were then compared to a UK population control to identify novel PBC risk loci and fine-map association signals. (Liu &amp; Almarri et al., Nat Genet, 2012)","abstract":"We genotyped 2,861 cases of primary biliary cirrhosis (PBC) from the UK PBC Consortium and 8,514 UK population controls across 196,524 variants within 186 known autoimmune risk loci. We identified 3 loci newly associated with PBC (at P &lt; 5 × 10-8), increasing the number of known susceptibility loci to 25. The most associated variant at 19p12 is a low-frequency nonsynonymous SNP in TYK2, further implicating JAK-STAT and cytokine signaling in disease pathogenesis. An additional five loci contained nonsynonymous variants in high linkage disequilibrium (LD; r2 &gt; 0.8) with the most associated variant at the locus. We found multiple independent common, low-frequency and rare variant association signals at five loci. Of the 26 independent non–human leukocyte antigen (HLA) signals tagged on the Immunochip, 15 have SNPs in B-lymphoblastoid open chromatin regions in high LD (r2 &gt; 0.8) with the most associated variant. This study shows how data from dense fine-mapping arrays coupled with functional genomic data can be used to identify candidate causal variants for functional follow-up.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-18T09:22:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001838","title":"Genome-wide quantification of rare somatic mutations in normal human tissues using massively parallel sequencing","description":"We present Bottleneck Sequencing System (BotSeqS), a nextgeneration sequencing method that simultaneously quantifies rare somatic point mutations across the mitochondrial and nuclear genomes. BotSeqS combines molecular barcoding with a simple dilution step immediately prior to library amplification. We use BotSeqS to show age and tissue-dependent accumulations of rare mutations and demonstrate that somatic mutational burden in normal tissues can vary by several orders of magnitude, depending on biologic and environmental factors. We further show major differences between the mutational patterns of the mitochondrial and nuclear genomes in normal tissues. Lastly, the mutation spectra of normal tissues were different from each other, but similar to those of the cancers that arose in them. This technology can provide insights into the number and nature of genetic alterations in normal tissues and can be used to address a variety of fundamental questions about the genomes of diseased tissues.","abstract":"We present Bottleneck Sequencing System (BotSeqS), a nextgeneration sequencing method that simultaneously quantifies rare somatic point mutations across the mitochondrial and nuclear genomes. BotSeqS combines molecular barcoding with a simple dilution step immediately prior to library amplification. We use BotSeqS to show age and tissue-dependent accumulations of rare mutations and demonstrate that somatic mutational burden in normal tissues can vary by several orders of magnitude, depending on biologic and environmental factors. We further show major differences between the mutational patterns of the mitochondrial and nuclear genomes in normal tissues. Lastly, the mutation spectra of normal tissues were different from each other, but similar to those of the cancers that arose in them. This technology can provide insights into the number and nature of genetic alterations in normal tissues and can be used to address a variety of fundamental questions about the genomes of diseased tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-18T15:36:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001839","title":"Circulating Tumor DNA Analysis Detects Minimal Residual Disease and Predicts Recurrence in Patients with Stage II Colon Cancer","description":"Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify those at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively-parallel-sequencing–based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected post-operatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of the 164 patients with negative ctDNA (HR, 18; 95% confidence interval [CI], 7.9 to 36; P&lt;0.001). In patients treated with chemotherapy, the presence of ctDNA following completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8  to 68; P=0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence.","abstract":"Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify those at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively-parallel-sequencing–based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected post-operatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of the 164 patients with negative ctDNA (HR, 18; 95% confidence interval [CI], 7.9 to 36; P&lt;0.001). In patients treated with chemotherapy, the presence of ctDNA following completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8  to 68; P=0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence.","study_type":"Other","pubmed_ids":[27384348],"external_links":null,"is_released":true,"released_date":"2016-05-18T19:05:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001840","title":"RNA-seq analysis of megakaryocytes and granulocytes in Quebec platelet disorder","description":"Quebec Platelet disorder (QPD) is a unique bleeding disorder that markedly increases urokinase plasminogen activator (uPA) in megakaryocytes and platelets but not in plasma or urine. The cause is tandem duplication of a 77 kb region of chromosome 10 containing PLAU and C10orf55. Blood cells and cultured megakaryocytes from donors (7 QPD, 10 control subjects) were prepared for total and allele-specific, quantitative reverse transcription polymerase chain reaction, immunoassays, Western blots and RNA-seq. Transcriptomes for cultured megakaryocytes and peripheral blood granulocytes from 4 control and 3 QPD individuals were analyzed using mRNA-seq.","abstract":"Quebec Platelet disorder (QPD) is a unique bleeding disorder that markedly increases urokinase plasminogen activator (uPA) in megakaryocytes and platelets but not in plasma or urine. The cause is tandem duplication of a 77 kb region of chromosome 10 containing PLAU and C10orf55. Blood cells and cultured megakaryocytes from donors (7 QPD, 10 control subjects) were prepared for total and allele-specific, quantitative reverse transcription polymerase chain reaction, immunoassays, Western blots and RNA-seq. Transcriptomes for cultured megakaryocytes and peripheral blood granulocytes from 4 control and 3 QPD individuals were analyzed using mRNA-seq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-18T21:55:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001841","title":"The dataset of Southeast Borneo individuals (Banjar and Ngaju ethnic groups) was used as comparative data to determine the Asian parental population of the Malagasy. Our study found strong support for an origin of the Asian ancestry of Malagasy among the Banjar.","description":"Malagasy genetic diversity results from an exceptional proto-globalisation process that took place over a thousand years ago across the Indian Ocean. Previous efforts to locate the Asian origin of Malagasy have highlighted Borneo broadly as a potential source, but so far no firm source populations have been identified. Here, we have generated genome-wide data from two Southeast Borneo populations, the Banjar and the Ngaju, together with published data compiled from populations across the Indian Ocean region. We find strong support for an origin of the Asian ancestry of Malagasy among the Banjar. This group emerged from the long-standing presence of a Malay Empire trading post in Southeast Borneo, which favoured admixture between the Malay and an autochthonous Borneo group, the Ma’anyan. Reconciling genetic, historical and linguistic data, we show that the Banjar, in Malay-led voyages, were the most probable Asian source among the analysed groups in the founding of the Malagasy gene pool.","abstract":"Malagasy genetic diversity results from an exceptional proto-globalisation process that took place over a thousand years ago across the Indian Ocean. Previous efforts to locate the Asian origin of Malagasy have highlighted Borneo broadly as a potential source, but so far no firm source populations have been identified. Here, we have generated genome-wide data from two Southeast Borneo populations, the Banjar and the Ngaju, together with published data compiled from populations across the Indian Ocean region. We find strong support for an origin of the Asian ancestry of Malagasy among the Banjar. This group emerged from the long-standing presence of a Malay Empire trading post in Southeast Borneo, which favoured admixture between the Malay and an autochthonous Borneo group, the Ma’anyan. Reconciling genetic, historical and linguistic data, we show that the Banjar, in Malay-led voyages, were the most probable Asian source among the analysed groups in the founding of the Malagasy gene pool.","study_type":"Other","pubmed_ids":[27381999],"external_links":null,"is_released":true,"released_date":"2016-05-19T15:45:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001842","title":"ALFRED TESTING","description":"This is a study","abstract":"This is a study","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001843","title":"The genome assembly project of Durio zibethinus","description":"Durian (Durio zibethinus) is a South East Asian tropical plant species, well-known for its hefty spine-covered fruit and notorious odor, sometimes described as sulfury or onion-like. Here, we present a draft genome assembly of D. zibethinus—the third plant genus in the Malvales order and the first in its Helicteroideae subfamily. Comparative phylogenomics suggests a recent paleopolyploidy event in the durian lineage, distinct from whole-genome duplications described for cotton, another Malvales member. Transcriptomic comparisons between different durian plant organs, and across fruits from different evolutionary lineages, revealed upregulation of sulfur, ethylene, and lipid-related pathways in durian fruits, consistent with the latter’s striking phenotypic traits. Similar comparisons between distinct durian fruit cultivars (Musang King, Monthong, Puyat) also yielded molecular rationales for within-cultivar differences in smell and taste. We identified, within the durian lineage, specific gene family expansions in sulfur processing and in particular the MGL gene, which catalyzes production of volatile sulfur compounds (VSCs). Both MGL and the ethylene-related gene ACS are upregulated in durian fruits, suggesting that VSC production and ripening may be coupled by the Yang cycle, a biosynthetic pathway linking ethylene biosynthesis to methionine regeneration. The durian draft genome provides a valuable resource for tropical fruit biology and agronomy.","abstract":"Durian (Durio zibethinus) is a South East Asian tropical plant species, well-known for its hefty spine-covered fruit and notorious odor, sometimes described as sulfury or onion-like. Here, we present a draft genome assembly of D. zibethinus—the third plant genus in the Malvales order and the first in its Helicteroideae subfamily. Comparative phylogenomics suggests a recent paleopolyploidy event in the durian lineage, distinct from whole-genome duplications described for cotton, another Malvales member. Transcriptomic comparisons between different durian plant organs, and across fruits from different evolutionary lineages, revealed upregulation of sulfur, ethylene, and lipid-related pathways in durian fruits, consistent with the latter’s striking phenotypic traits. Similar comparisons between distinct durian fruit cultivars (Musang King, Monthong, Puyat) also yielded molecular rationales for within-cultivar differences in smell and taste. We identified, within the durian lineage, specific gene family expansions in sulfur processing and in particular the MGL gene, which catalyzes production of volatile sulfur compounds (VSCs). Both MGL and the ethylene-related gene ACS are upregulated in durian fruits, suggesting that VSC production and ripening may be coupled by the Yang cycle, a biosynthetic pathway linking ethylene biosynthesis to methionine regeneration. The durian draft genome provides a valuable resource for tropical fruit biology and agronomy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001844","title":"Targeting FGFR1 for treatment of soft-tissue sarcoma (H021)","description":"Purpose: Altered FGFR1 signaling has emerged as therapeutic target in various epithelial malignancies. In contrast, the role of FGFR1 in soft-tissue sarcoma (STS) has not been established. Prompted by the detection and subsequent therapeutic inhibition of amplified FGFR1 in a patient with metastatic leiomyosarcoma, we investigated the oncogenic properties and potential as drug target of FGFR1 in STS.Experimental Design: The frequency of FGFR1 amplification and overexpression, as assessed by fluorescence in situ hybridization, microarray-based comparative genomic hybridization and mRNA expression profiling, SNP array profiling, and RNA sequencing, was determined in three independent patient cohorts. The sensitivity of STS cell lines with or without FGFR1 alterations to genetic and pharmacologic FGFR1 inhibition and the signaling pathways engaged by FGFR1 were investigated using short-term viability assays, long-term colony formation assays, and biochemical analysis.Results: Increased FGFR1 copy number was detected in 74 of 190 (38.9%; Cohort 1), 13 of 79 (16.5%; Cohort 2), and 80 of 254 (31.5%; Cohort 3) patients. FGFR1 overexpression occurred in 16 of 79 (20.2%, Cohort 2) and 39 of 254 (15.4%; Cohort 3) patients. Targeting of FGFR1 by short hairpin RNA-mediated knockdown and different small-molecule inhibitors (PD173074, AZD4547, BGJ398) revealed that the requirement for FGFR1 signaling in STS cells is primarily dictated by FGFR1 expression levels, and identified the MAPK-ERK1/2 axis as critical FGFR1 effector pathway.Conclusion: These data identify FGFR1 as driver gene in multiple STS subtypes and support FGFR1 inhibition, guided by patient selection according to FGFR1 expression and monitoring of MAPK-ERK1/2 signaling, as therapeutic option in this challenging group of diseases.H021","abstract":"Purpose: Altered FGFR1 signaling has emerged as therapeutic target in various epithelial malignancies. In contrast, the role of FGFR1 in soft-tissue sarcoma (STS) has not been established. Prompted by the detection and subsequent therapeutic inhibition of amplified FGFR1 in a patient with metastatic leiomyosarcoma, we investigated the oncogenic properties and potential as drug target of FGFR1 in STS.Experimental Design: The frequency of FGFR1 amplification and overexpression, as assessed by fluorescence in situ hybridization, microarray-based comparative genomic hybridization and mRNA expression profiling, SNP array profiling, and RNA sequencing, was determined in three independent patient cohorts. The sensitivity of STS cell lines with or without FGFR1 alterations to genetic and pharmacologic FGFR1 inhibition and the signaling pathways engaged by FGFR1 were investigated using short-term viability assays, long-term colony formation assays, and biochemical analysis.Results: Increased FGFR1 copy number was detected in 74 of 190 (38.9%; Cohort 1), 13 of 79 (16.5%; Cohort 2), and 80 of 254 (31.5%; Cohort 3) patients. FGFR1 overexpression occurred in 16 of 79 (20.2%, Cohort 2) and 39 of 254 (15.4%; Cohort 3) patients. Targeting of FGFR1 by short hairpin RNA-mediated knockdown and different small-molecule inhibitors (PD173074, AZD4547, BGJ398) revealed that the requirement for FGFR1 signaling in STS cells is primarily dictated by FGFR1 expression levels, and identified the MAPK-ERK1/2 axis as critical FGFR1 effector pathway.Conclusion: These data identify FGFR1 as driver gene in multiple STS subtypes and support FGFR1 inhibition, guided by patient selection according to FGFR1 expression and monitoring of MAPK-ERK1/2 signaling, as therapeutic option in this challenging group of diseases.H021","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-23T08:10:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001845","title":"Mutant KIT as imatinib-sensitive target in metastatic sinonasal carcinoma (H021)","description":"Sinonasal carcinomas (SNCs) comprise various rare tumor types that are characterized by marked histologic diversity and largely unknown molecular profiles, yet share an overall poor prognosis owing to an aggressive clinical course and frequent late-stage diagnosis. The lack of effective systemic therapies for locally advanced or metastatic SNC poses a major challenge to therapeutic decision making for individual patients. Here, we used whole-exome and transcriptome sequencing to identify a KIT exon 11 mutation (c.1733_1735del, p.578_579del) as actionable target in a patient with metastatic SNC whose tumor, despite all diagnostic efforts, could not be assigned to any known SNC category and was refractory to multimodal therapy. Molecularly guided treatment with imatinib resulted in a dramatic and durable response with remission of nearly all tumor manifestations, indicating a dominant driver function of mutant KIT in this tumor. This observation highlights the potential of unbiased genomic profiling for uncovering the vulnerabilities of individual malignancies, particularly in rare and unclassifiable tumors, and underscores that KIT exon 11 mutations represent tractable therapeutic targets across different histologies.H021","abstract":"Sinonasal carcinomas (SNCs) comprise various rare tumor types that are characterized by marked histologic diversity and largely unknown molecular profiles, yet share an overall poor prognosis owing to an aggressive clinical course and frequent late-stage diagnosis. The lack of effective systemic therapies for locally advanced or metastatic SNC poses a major challenge to therapeutic decision making for individual patients. Here, we used whole-exome and transcriptome sequencing to identify a KIT exon 11 mutation (c.1733_1735del, p.578_579del) as actionable target in a patient with metastatic SNC whose tumor, despite all diagnostic efforts, could not be assigned to any known SNC category and was refractory to multimodal therapy. Molecularly guided treatment with imatinib resulted in a dramatic and durable response with remission of nearly all tumor manifestations, indicating a dominant driver function of mutant KIT in this tumor. This observation highlights the potential of unbiased genomic profiling for uncovering the vulnerabilities of individual malignancies, particularly in rare and unclassifiable tumors, and underscores that KIT exon 11 mutations represent tractable therapeutic targets across different histologies.H021","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-23T09:30:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001846","title":"Integration of genomics and histology reveals diagnosis and effective therapy of refractory cancer of unknown primary with PDL1 amplification (H021)","description":"Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multi-agent chemotherapy. Molecular profiling within a clinical whole-exome and transcriptome sequencing program revealed a heterozygous, highly amplified KRAS G12S mutation, compound-heterozygous TP53 mutation/deletion, high mutational load, and focal amplification of chromosomes 9p (including PDL1 [CD274] and JAK2) and 10p (including GATA3). Integrated analysis of molecular data and conventional histopathology suggested a diagnosis of triple-negative breast cancer (TNBC) and provided a rationale for immune checkpoint inhibitor therapy with pembrolizumab, which resulted in rapid clinical improvement and a lasting partial remission. Analysis of 157 TNBC samples from The Cancer Genome Atlas revealed focal, high-level PDL1 amplification coinciding with excessive PDL1 mRNA expression in 24% of cases. Collectively, these results illustrate the diagnostic utility of multidimensional tumor profiling in cases with non-descript histology and immune phenotype, demonstrate the predictive power of genomic PDL1 amplification for immune checkpoint inhibition, and suggest a targeted therapeutic strategy in chromosome 9p24.1/PDL1-amplified cancers.H021","abstract":"Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multi-agent chemotherapy. Molecular profiling within a clinical whole-exome and transcriptome sequencing program revealed a heterozygous, highly amplified KRAS G12S mutation, compound-heterozygous TP53 mutation/deletion, high mutational load, and focal amplification of chromosomes 9p (including PDL1 [CD274] and JAK2) and 10p (including GATA3). Integrated analysis of molecular data and conventional histopathology suggested a diagnosis of triple-negative breast cancer (TNBC) and provided a rationale for immune checkpoint inhibitor therapy with pembrolizumab, which resulted in rapid clinical improvement and a lasting partial remission. Analysis of 157 TNBC samples from The Cancer Genome Atlas revealed focal, high-level PDL1 amplification coinciding with excessive PDL1 mRNA expression in 24% of cases. Collectively, these results illustrate the diagnostic utility of multidimensional tumor profiling in cases with non-descript histology and immune phenotype, demonstrate the predictive power of genomic PDL1 amplification for immune checkpoint inhibition, and suggest a targeted therapeutic strategy in chromosome 9p24.1/PDL1-amplified cancers.H021","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-23T09:36:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001847","title":"Genomic and transcriptional landscape of P2RY8-CRLF2-positive childhood acute lymphoblastic leukemia","description":"The mutational and transcriptional landscape of P2RY8-CRLF2-positive ALL was defined in 41 major clone fusion-positive cases including 19 matched diagnosis and relapse pairs by an integrated analysis of whole-exome and RNA sequencing. We detected a variety of frequently subclonal and highly unstable JAK/STAT but also RTK/Ras pathway activating mutations in 76% of cases at diagnosis and virtually all relapses. Unlike P2RAY8-CRLF2 that was lost in 32% of relapses, all other genomic deletions affecting lymphoid development and cell cycle remained stable. Only IKZF1 alterations predominated in relapsing cases and increased from initially 36 to 58% in matched cases. IKZF1¹s transcriptional signature revealed compromised stem cell features with signs of impaired lymphoid differentiation, enhanced focal adhesion, activated hypoxia pathway, deregulated cell cycle and increased drug resistance.","abstract":"The mutational and transcriptional landscape of P2RY8-CRLF2-positive ALL was defined in 41 major clone fusion-positive cases including 19 matched diagnosis and relapse pairs by an integrated analysis of whole-exome and RNA sequencing. We detected a variety of frequently subclonal and highly unstable JAK/STAT but also RTK/Ras pathway activating mutations in 76% of cases at diagnosis and virtually all relapses. Unlike P2RAY8-CRLF2 that was lost in 32% of relapses, all other genomic deletions affecting lymphoid development and cell cycle remained stable. Only IKZF1 alterations predominated in relapsing cases and increased from initially 36 to 58% in matched cases. IKZF1¹s transcriptional signature revealed compromised stem cell features with signs of impaired lymphoid differentiation, enhanced focal adhesion, activated hypoxia pathway, deregulated cell cycle and increased drug resistance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-23T15:44:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001848","title":"Evolution of a FLT3-TKD mutated subclone at meningeal relapse in acute promyelocytic leukemia (H021)","description":"Here we report the case of an acute promyelocytic leukemia (APL) patient who, though negative for FLT3 mutations at diagnosis, developed isolated FLT3-TKD positive meningeal relapse, which, in retrospect, could be traced back to a minute bone marrow subclone present at first diagnosis. Initially, the 48-year old female diagnosed with high-risk APL had achieved complete molecular remission after standard treatment with all-trans retinoic acid (ATRA) and chemotherapy according to the AIDA protocol. 13 months after start of ATRA maintenance the patient suffered clinically overt meningeal relapse along with minute molecular traces of PML/RARA in the bone marrow. Following treatment with arsenic trioxide (ATO) and ATRA in combination with intrathecal cytarabine and methotrexate, the patient achieved a complete molecular remission in both cerebrospinal fluid (CSF) and bone marrow, which currently lasts for two years after completion of therapy. Whole exome sequencing and subsequent ultradeep targeted re-sequencing revealed a heterozygous FLT3-TKD mutation in CSF leukemic cells (p.D835Y, c.2503G&gt;T, 1000/1961 reads (51%)), which was undetectable in the concurrent bone marrow sample. Interestingly, the FLT3-TKD mutated meningeal clone originated from a small bone marrow subclone present in a variant allele frequency of 0.4% (6/1553 reads) at initial diagnosis. This case highlights the concept of clonal evolution with a subclone harboring an additional mutation being selected as the “fittest” and leading to meningeal relapse. It also further supports earlier suggestions that FLT3 mutations may play a role for migration and clonal expansion in the CSF sanctuary site.H021","abstract":"Here we report the case of an acute promyelocytic leukemia (APL) patient who, though negative for FLT3 mutations at diagnosis, developed isolated FLT3-TKD positive meningeal relapse, which, in retrospect, could be traced back to a minute bone marrow subclone present at first diagnosis. Initially, the 48-year old female diagnosed with high-risk APL had achieved complete molecular remission after standard treatment with all-trans retinoic acid (ATRA) and chemotherapy according to the AIDA protocol. 13 months after start of ATRA maintenance the patient suffered clinically overt meningeal relapse along with minute molecular traces of PML/RARA in the bone marrow. Following treatment with arsenic trioxide (ATO) and ATRA in combination with intrathecal cytarabine and methotrexate, the patient achieved a complete molecular remission in both cerebrospinal fluid (CSF) and bone marrow, which currently lasts for two years after completion of therapy. Whole exome sequencing and subsequent ultradeep targeted re-sequencing revealed a heterozygous FLT3-TKD mutation in CSF leukemic cells (p.D835Y, c.2503G&gt;T, 1000/1961 reads (51%)), which was undetectable in the concurrent bone marrow sample. Interestingly, the FLT3-TKD mutated meningeal clone originated from a small bone marrow subclone present in a variant allele frequency of 0.4% (6/1553 reads) at initial diagnosis. This case highlights the concept of clonal evolution with a subclone harboring an additional mutation being selected as the “fittest” and leading to meningeal relapse. It also further supports earlier suggestions that FLT3 mutations may play a role for migration and clonal expansion in the CSF sanctuary site.H021","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-23T20:08:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001849","title":"Whole-genome sequencing of two probands with hereditary spastic paraplegia reveals novel splice-donor region mutation and known pathogenic mutation in SPG11","description":"Hereditary spastic paraplegias (SPG) are a group of heterogeneous neurodegenerative disorders, which are often presented with overlapping phenotypes such as progressive paraparesis and spasticity. To assist the diagnosis of SPG subtypes, next-generation sequencing is often used to provide supporting evidence. In this study, we report the case of two probands from the same family with SPG symptoms, including bilateral lower limbs weakness, unsteady gait, cognitive decline, dysarthria and slurring of speech since age of 14. Subsequent whole-genome sequencing revealed that the patients are compound heterozygous for mutations in SPG11 gene, including the paternally inherited c.6856C&gt;T (p.Arg2286*) mutation and the novel maternally inherited c.2316+5G&gt;A splice donor region mutation. Mutations in SPG11 are the common cause of autosomal recessive Spastic Paraplegia type 11. According to the ClinVar database, there are already 101 reported pathogenic mutations in SPG11 that are associated with SPG. To our knowledge, this is the first report of SPG11 mutations in our local population. Novel splice mutation identified in this study would enrich the catalog of SPG11 mutations, potentially leading to better genetic diagnosis of SPG.","abstract":"Hereditary spastic paraplegias (SPG) are a group of heterogeneous neurodegenerative disorders, which are often presented with overlapping phenotypes such as progressive paraparesis and spasticity. To assist the diagnosis of SPG subtypes, next-generation sequencing is often used to provide supporting evidence. In this study, we report the case of two probands from the same family with SPG symptoms, including bilateral lower limbs weakness, unsteady gait, cognitive decline, dysarthria and slurring of speech since age of 14. Subsequent whole-genome sequencing revealed that the patients are compound heterozygous for mutations in SPG11 gene, including the paternally inherited c.6856C&gt;T (p.Arg2286*) mutation and the novel maternally inherited c.2316+5G&gt;A splice donor region mutation. Mutations in SPG11 are the common cause of autosomal recessive Spastic Paraplegia type 11. According to the ClinVar database, there are already 101 reported pathogenic mutations in SPG11 that are associated with SPG. To our knowledge, this is the first report of SPG11 mutations in our local population. Novel splice mutation identified in this study would enrich the catalog of SPG11 mutations, potentially leading to better genetic diagnosis of SPG.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-25T05:33:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001850","title":"African population genetic analysis dataset","description":"This release provides a computationally phased dataset of 4216 individuals from 48 African and 12 Eurasian populations typed at 328,000 autosomal SNPs. This dataset was used in Busby et al (eLife, 2016): Admixture into and within sub-Saharan Africa. We combined data from the MalariaGEN project with publicly available data from the One Thousand Genomes project and several other sources to understand the recent admixture history of Africa. Details of the populations used, and there origin, are available in the README","abstract":"This release provides a computationally phased dataset of 4216 individuals from 48 African and 12 Eurasian populations typed at 328,000 autosomal SNPs. This dataset was used in Busby et al (eLife, 2016): Admixture into and within sub-Saharan Africa. We combined data from the MalariaGEN project with publicly available data from the One Thousand Genomes project and several other sources to understand the recent admixture history of Africa. Details of the populations used, and there origin, are available in the README","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001851","title":"Korean Diffuse gastric cancer","description":"Gastric cancers in young patients are aggressive and predominantly of diffuse histology. Also, they are more frequent in female. To identify recurrent somatic alterations in this unique subset of gastric cancers, whole exome and transcriptome analyses were performed using frozen cancer tissue. The same analyses were also performed using adjacent normal tissue (mRNA) or blood (exome) of the same patients.","abstract":"Gastric cancers in young patients are aggressive and predominantly of diffuse histology. Also, they are more frequent in female. To identify recurrent somatic alterations in this unique subset of gastric cancers, whole exome and transcriptome analyses were performed using frozen cancer tissue. The same analyses were also performed using adjacent normal tissue (mRNA) or blood (exome) of the same patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001852","title":"Population_sequencing_phasing","description":"Whole-genome sequencing of human individuals from Polynesian and Native American populations, as well as 10x Genomics Chromium data from Polynesian, Native American and Aboriginal Australian populations, allowing for experimental phasing of haplotypes.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"This study has two components. The first is whole-genome sequencing on the Illumina HiSeqX of 24 Polynesian genomes from two different locations (the western Samoan Islands and the Austral Islands) and 44 from two Native American populations. The second component is sequencing of two individuals from each of these Polynesian and Native American populations plus two Aboriginal Australian individuals (10 in total) using the 10x Genomics Chromium platform, to allow for experimental phasing of haplotypes. These data will enable studies of population history and demographics of Oceanian and Native Americans.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-26T14:03:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001853","title":"Australia_and_New_Guinea_haplotype_phasing_","description":"Whole-genome sequencing and phasing of admixed Aboriginal Australian genomes and Papua New Guinean genomes using 10x Genomics Chromium technology.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Four individuals from admixed Aboriginal Australian populations and four from populations in Papua New Guinea are sequenced using 10x Genomics Chromium technology, to allow for experimental phasing of haplotypes.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-26T15:14:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001854","title":"Clonal expansion and epigenetic reprogramming following deletion or amplification of mutant IDH1","description":"IDH1 mutation is the earliest genetic alteration in low-grade gliomas (LGGs), but its role in tumor recurrence is unclear. Mutant IDH1 drives overproduction of the oncometabolite D-2-hydroxyglutarate (2HG) and a CpG island (CGI) hypermethylation phenotype (G-CIMP). To investigate the role of mutant IDH1 at recurrence, we performed a longitudinal analysis of 50 IDH1 mutant LGGs. We discovered six cases with copy number alterations (CNAs) at the IDH1 locus at recurrence. Deletion or amplification of IDH1 was followed by clonal expansion and recurrence at a higher grade. Successful cultures derived from IDH1 mutant, but not IDH1 wild-type, gliomas systematically deleted IDH1 in vitro and in vivo, further suggestive of selection against the heterozygous mutant state as tumors progress. Tumors and cultures with IDH1 CNA had decreased 2HG, maintenance of G-CIMP, and DNA methylation reprogramming outside CGI. Thus, while IDH1 mutation initiates gliomagenesis, in some patients, mutant IDH1 and 2HG are not required for later clonal expansions.","abstract":"IDH1 mutation is the earliest genetic alteration in low-grade gliomas (LGGs), but its role in tumor recurrence is unclear. Mutant IDH1 drives overproduction of the oncometabolite D-2-hydroxyglutarate (2HG) and a CpG island (CGI) hypermethylation phenotype (G-CIMP). To investigate the role of mutant IDH1 at recurrence, we performed a longitudinal analysis of 50 IDH1 mutant LGGs. We discovered six cases with copy number alterations (CNAs) at the IDH1 locus at recurrence. Deletion or amplification of IDH1 was followed by clonal expansion and recurrence at a higher grade. Successful cultures derived from IDH1 mutant, but not IDH1 wild-type, gliomas systematically deleted IDH1 in vitro and in vivo, further suggestive of selection against the heterozygous mutant state as tumors progress. Tumors and cultures with IDH1 CNA had decreased 2HG, maintenance of G-CIMP, and DNA methylation reprogramming outside CGI. Thus, while IDH1 mutation initiates gliomagenesis, in some patients, mutant IDH1 and 2HG are not required for later clonal expansions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-26T22:09:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001855","title":"Low_input_LC__WGS_","description":"R&amp;D project to develop low input library construction methods.","abstract":"R&amp;D project to develop low input library construction methods.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-27T08:54:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001856","title":"Low_input_LC__ISC_","description":"R&amp;D project to develop low input library construction methods.","abstract":"R&amp;D project to develop low input library construction methods.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-27T08:58:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001857","title":"Genetic subclone heterogeneity of tumor-initiating cells in human colorectal cancer","description":"A subset of tumor-initiating cells (TIC) drives colorectal cancer (CRC) progression in serial mouse xenografts. The TIC compartment itself is heterogeneous and comprises hierarchically organized long-term TIC, tumor transient amplifying cells, and delayed contributing TIC. To address the genomic heterogeneity of the CRC TIC compartment, genome-wide high-coverage whole genome sequencing was performed on patient tumors (n=3), corresponding serially passaged TIC-enriched spheres, and serial xenografts.HIPO P002","abstract":"A subset of tumor-initiating cells (TIC) drives colorectal cancer (CRC) progression in serial mouse xenografts. The TIC compartment itself is heterogeneous and comprises hierarchically organized long-term TIC, tumor transient amplifying cells, and delayed contributing TIC. To address the genomic heterogeneity of the CRC TIC compartment, genome-wide high-coverage whole genome sequencing was performed on patient tumors (n=3), corresponding serially passaged TIC-enriched spheres, and serial xenografts.HIPO P002","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-29T17:53:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001858","title":"Whole transcriptome and exome sequencing of childhood ALL","description":"Gene fusion is a major class of genomic abnormalities in childhood acute lymphoblastic leukemia (ALL) and sentinel chromosomal rearrangements involving EP300 and CREBBP may cause global epigenetic deregulation during leukemogenesis with potentials for therapeutic targeting. This dataset includes whole transcriptome sequencing of 231 children with acute lymphoblastic leukemia from a Singapore-Malaysia frontline clinical treatment protocol.","abstract":"Gene fusion is a major class of genomic abnormalities in childhood acute lymphoblastic leukemia (ALL) and sentinel chromosomal rearrangements involving EP300 and CREBBP may cause global epigenetic deregulation during leukemogenesis with potentials for therapeutic targeting. This dataset includes whole transcriptome sequencing of 231 children with acute lymphoblastic leukemia from a Singapore-Malaysia frontline clinical treatment protocol.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-05-31T15:25:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001859","title":"Transcriptome profiling for Korean Diffuse Gastric cancers","description":"Gastric cancers in young patients are aggressive and predominantly of diffuse histology. Also, they are more frequent in female. To identify transcriptome profile in this unique subset of gastric cancers, RNA-seq analyses were performed using frozen cancer tissue. Adjacent normal tissue of the same patients were used in differently expressed gene selection and fusion gene prediction.","abstract":"Gastric cancers in young patients are aggressive and predominantly of diffuse histology. Also, they are more frequent in female. To identify transcriptome profile in this unique subset of gastric cancers, RNA-seq analyses were performed using frozen cancer tissue. Adjacent normal tissue of the same patients were used in differently expressed gene selection and fusion gene prediction.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-06-01T02:08:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001860","title":"Periprostatic tissue obtained from patients with from high-risk prostate cancer has a distinct transcriptional profile","description":"Purpose: Increasing evidence indicates that altered adipose tissue homeostasis may be an important contributor to the development and/or progression of prostate cancer. As prostate tumours progress locally they frequently invade the periprostatic adipose compartment, gaining access to locally produced adipokines that have been associated with tumour cell growth, invasion and metastases. In this study we investigate the adipose transcriptional profiles of high-risk and low-risk disease to determine both prognostic potential and possible biological drivers of aggressive disease.Experimental Design: RNA was extracted from periprostatic and subcutaneous adipose tissue taken from patients categorised as having prostate cancer with either a high- or low-risk of progression by the D’Amico classification system and profiled by gene-expression microarray.Results: A clear separation was observed between the transcriptional profiles of high-risk and low-risk prostate cancer in periprostatic adipose tissue and a 10-gene signature consisting of CXORF39, PTGR1, CTNNA1, CDK8, TMEM64, LAMP3, LMO3, RGS16, SVEP1, and MEF2A, was able to separate high- and low-risk disease. Furthermore, similarities observed between periprostatic and subcutaneous adipose tissues may indicate a systemic contribution of adipose tissue to prostate cancer.Conclusions: Periprostatic adipose tissue is contributing to the tumour microenvironment of prostate cancer and affecting the progression of the disease.","abstract":"Purpose: Increasing evidence indicates that altered adipose tissue homeostasis may be an important contributor to the development and/or progression of prostate cancer. As prostate tumours progress locally they frequently invade the periprostatic adipose compartment, gaining access to locally produced adipokines that have been associated with tumour cell growth, invasion and metastases. In this study we investigate the adipose transcriptional profiles of high-risk and low-risk disease to determine both prognostic potential and possible biological drivers of aggressive disease.Experimental Design: RNA was extracted from periprostatic and subcutaneous adipose tissue taken from patients categorised as having prostate cancer with either a high- or low-risk of progression by the D’Amico classification system and profiled by gene-expression microarray.Results: A clear separation was observed between the transcriptional profiles of high-risk and low-risk prostate cancer in periprostatic adipose tissue and a 10-gene signature consisting of CXORF39, PTGR1, CTNNA1, CDK8, TMEM64, LAMP3, LMO3, RGS16, SVEP1, and MEF2A, was able to separate high- and low-risk disease. Furthermore, similarities observed between periprostatic and subcutaneous adipose tissues may indicate a systemic contribution of adipose tissue to prostate cancer.Conclusions: Periprostatic adipose tissue is contributing to the tumour microenvironment of prostate cancer and affecting the progression of the disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001861","title":"Molecular evolution of metastatic clear cell renal cell carcinoma progressing under tyrosine kinase inhibitor therapy (HIPO-045)","description":"Background:Acquired resistance to targeted drugs is largely due to intra-tumor molecular heterogeneity and clonal selection. Objective:The objective of this study was to determine molecular alterations and mediating resistant mechanisms and to suggest additional treatment options.Design, Setting, and Participants:Four patients were enrolled into the MORE (Molecular Renal Cancer Evolution) trial. We investigated the mutational spectra of metastatic clear cell renal cell carcinoma (ccRCC) at baseline and compared them to those upon clonal evolution at progression on systemic therapy with tyrosine kinase inhibitors.Outcome Measurements:DNA was isolated from tumor tissues after surgery, metastasis biopsies after progression on sunitinib or axitinib, and subjected to whole-exome sequencing (WES). In addition, the exomes of circulating tumor DNA (ctDNA) from two patients were sequenced at baseline and at progression.Results and Limitations:Our data provide evidence for clonal evolution and various acquired resistance mechanisms of ccRCC with subclonal mutations in FLT4, MTOR, ITGA3/5, SETD2, and VHL on metastatic progression. The limited number of shared mutations in tissue and plasma biopsies indicates that both sources provide complementary information, possibly due to mutations present in metastatic lesions which were not amenable to tissue sampling but are represented in the ctDNA. Conclusion:Acquired resistance to targeted therapies in metastatic ccRCC is due to intra-tumor heterogeneity and clonal evolution. Larger patient cohorts have to be studied to estimate the benefit of WES from biopsies and ctDNA for therapy decision in metastatic ccRCC.Patient Summary:We analyzed the molecular profiles of ccRCC patients in primary tissues and metastatic tissues upon progression on tyrosine kinase inhibitor therapy. Clinically relevant mutations upon progression were detected in the metastatic sites of all of four patients, suggesting that it might be possible to derive therapies based on sequencing the metastases.?HIPO-045","abstract":"Background:Acquired resistance to targeted drugs is largely due to intra-tumor molecular heterogeneity and clonal selection. Objective:The objective of this study was to determine molecular alterations and mediating resistant mechanisms and to suggest additional treatment options.Design, Setting, and Participants:Four patients were enrolled into the MORE (Molecular Renal Cancer Evolution) trial. We investigated the mutational spectra of metastatic clear cell renal cell carcinoma (ccRCC) at baseline and compared them to those upon clonal evolution at progression on systemic therapy with tyrosine kinase inhibitors.Outcome Measurements:DNA was isolated from tumor tissues after surgery, metastasis biopsies after progression on sunitinib or axitinib, and subjected to whole-exome sequencing (WES). In addition, the exomes of circulating tumor DNA (ctDNA) from two patients were sequenced at baseline and at progression.Results and Limitations:Our data provide evidence for clonal evolution and various acquired resistance mechanisms of ccRCC with subclonal mutations in FLT4, MTOR, ITGA3/5, SETD2, and VHL on metastatic progression. The limited number of shared mutations in tissue and plasma biopsies indicates that both sources provide complementary information, possibly due to mutations present in metastatic lesions which were not amenable to tissue sampling but are represented in the ctDNA. Conclusion:Acquired resistance to targeted therapies in metastatic ccRCC is due to intra-tumor heterogeneity and clonal evolution. Larger patient cohorts have to be studied to estimate the benefit of WES from biopsies and ctDNA for therapy decision in metastatic ccRCC.Patient Summary:We analyzed the molecular profiles of ccRCC patients in primary tissues and metastatic tissues upon progression on tyrosine kinase inhibitor therapy. Clinically relevant mutations upon progression were detected in the metastatic sites of all of four patients, suggesting that it might be possible to derive therapies based on sequencing the metastases.?HIPO-045","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-06-01T10:11:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001862","title":"Recurrent somatic JAK-STAT mutations within a novel RUNX1-mutated pedigree","description":"The acquisition of somatic mutations is an emerging field of investigation in familial leukemia.  Currently, genetic profiles in familial MDS/AML are considered analogous to sporadic disease, although the patterns of clonal evolution within families are poorly defined.  We performed whole exome profiling of tumour samples from a novel RUNX1 mutated family, to determine the stepwise evolution of MDS/AML across 4 young siblings.  Three siblings developed monocytic AML/RAEB2 at 5 years of age, with hepatosplenomegaly and somatic mutations upregulating JAK-STAT signalling, the latter are typically detected in &lt;5% of sporadic MDS/AML.  Two siblings acquired the canonical JAK2 V617F mutation, while another acquired a unique missense mutation of SH2B3, a negative regulator of JAK2.  Notably, 2/3 siblings demonstrated dosage amplification of these mutations due to acquired uniparental disomy of chromosomes 9p and 12q (encompassing JAK2 and SH2B3, respectively).  All 4 siblings were heterozygous for the 46/1 JAK2 haplotype associated with predisposition to sporadic V617F myeloproliferative disorders, which likely influenced the acquisition of JAK2 mutations.  Our findings provide further evidence that relatives with shared germline mutations may acquire somatic mutations in a non-random manner leading to convergent patterns of disease evolution.","abstract":"The acquisition of somatic mutations is an emerging field of investigation in familial leukemia.  Currently, genetic profiles in familial MDS/AML are considered analogous to sporadic disease, although the patterns of clonal evolution within families are poorly defined.  We performed whole exome profiling of tumour samples from a novel RUNX1 mutated family, to determine the stepwise evolution of MDS/AML across 4 young siblings.  Three siblings developed monocytic AML/RAEB2 at 5 years of age, with hepatosplenomegaly and somatic mutations upregulating JAK-STAT signalling, the latter are typically detected in &lt;5% of sporadic MDS/AML.  Two siblings acquired the canonical JAK2 V617F mutation, while another acquired a unique missense mutation of SH2B3, a negative regulator of JAK2.  Notably, 2/3 siblings demonstrated dosage amplification of these mutations due to acquired uniparental disomy of chromosomes 9p and 12q (encompassing JAK2 and SH2B3, respectively).  All 4 siblings were heterozygous for the 46/1 JAK2 haplotype associated with predisposition to sporadic V617F myeloproliferative disorders, which likely influenced the acquisition of JAK2 mutations.  Our findings provide further evidence that relatives with shared germline mutations may acquire somatic mutations in a non-random manner leading to convergent patterns of disease evolution.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-06-01T18:04:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001863","title":"Whole exome sequencing of porphyria patients","description":"Whole exome sequencing of severely affected porphyria patients using SOLiD 5500xl platform to identify genetic modifiers that influence clinical penetrance of porphyria.","abstract":"Whole exome sequencing of severely affected porphyria patients using SOLiD 5500xl platform to identify genetic modifiers that influence clinical penetrance of porphyria.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001864","title":"RNA-sequencing data from primary pediatric acute lymphoblastic leukemia (ALL) patients.","description":"Strand-specific RNA-sequencing data was generated from RNA isolated from primary pediatric acute lymphoblastic leukemia (ALL) cells at diagnosis.","abstract":"Strand-specific RNA-sequencing data was generated from RNA isolated from primary pediatric acute lymphoblastic leukemia (ALL) cells at diagnosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001865","title":"Diagnostic Potential of Tumor DNA from Ovarian Cyst Fluid","description":"We determined whether the mutations found in ovarian cancers could be identified in the patients' ovarian cyst fluids.  Tumor-specific mutations were detectable in the cyst fluids of 19 of 23 (83%) borderline tumors, 10 of 13 (77%) type I cancers, and 18 of 18 (100%) type II cancers.  In contrast, no mutations were found in the cyst fluids of 18 patients with benign tumors or non-neoplastic cysts.  Though large, prospective studies are needed to demonstrate the safety and clinical utility of this approach, our results suggest that the genetic evaluation of cyst fluids might be able to inform the management of the large number of women with these lesions.","abstract":"We determined whether the mutations found in ovarian cancers could be identified in the patients' ovarian cyst fluids.  Tumor-specific mutations were detectable in the cyst fluids of 19 of 23 (83%) borderline tumors, 10 of 13 (77%) type I cancers, and 18 of 18 (100%) type II cancers.  In contrast, no mutations were found in the cyst fluids of 18 patients with benign tumors or non-neoplastic cysts.  Though large, prospective studies are needed to demonstrate the safety and clinical utility of this approach, our results suggest that the genetic evaluation of cyst fluids might be able to inform the management of the large number of women with these lesions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001866","title":"Subtype specific progression from DCIS to invasive breast cancer","description":"Breast cancer consists of at least five main molecular “intrinsic” subtypes, which are reflected in both pre-invasive and invasive disease. Although previous studies have suggested that many of the molecular features of invasive breast cancer are established early, it is unclear what mechanisms drive progression, and whether the mechanisms of progression are dependent or independent of subtype. We have generated mRNA, miRNA and DNA copy number profiles from a total of 59 in situ lesions and 85 invasive tumors, in order to comprehensively identify those genes, signaling pathways, processes, and cell types that are involved in breast cancer progression. Our work provides evidence that there are molecular features associated with disease progression that are unique to the intrinsic subtypes. We additionally establish subtype-specific signatures that are able to identify a small proportion of pre-invasive tumors with expression profiles that resemble invasive carcinoma, indicating a higher likelihood of future disease progression.","abstract":"Breast cancer consists of at least five main molecular “intrinsic” subtypes, which are reflected in both pre-invasive and invasive disease. Although previous studies have suggested that many of the molecular features of invasive breast cancer are established early, it is unclear what mechanisms drive progression, and whether the mechanisms of progression are dependent or independent of subtype. We have generated mRNA, miRNA and DNA copy number profiles from a total of 59 in situ lesions and 85 invasive tumors, in order to comprehensively identify those genes, signaling pathways, processes, and cell types that are involved in breast cancer progression. Our work provides evidence that there are molecular features associated with disease progression that are unique to the intrinsic subtypes. We additionally establish subtype-specific signatures that are able to identify a small proportion of pre-invasive tumors with expression profiles that resemble invasive carcinoma, indicating a higher likelihood of future disease progression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-06-07T19:41:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001867","title":"DDD_WGS","description":"We propose to apply state of the art molecular testing, including SNP genotyping, to 12,000 UK children with abnormal development. The results will provide a unique, on-line catalogue of genetic changes linked to symptoms that will enable clinicians to diagnose developmental disorders. Furthermore, we will design more efficient and cheaper diagnostic assays for relevant genetic testing to be offered to all such patients in the UK and so transform clinical practice for children with abnormal development.","abstract":"Thousands of babies are born each year in the UK who fail to develop normally because of errors in their genetic makeup. Currently, diagnosis is restricted to a small minority of children and requires the clinician to recognise the appearance of the child and the pattern of symptoms, supplemented by the use of microscopes to identify large rearrangements of the genetic material in chromosomes. Research shows that the latest molecular testing methods identify previously undetectable changes in chromosomes allowing new diagnoses to be made. However, clinical use is hampered by the limited availability and inconsistent application of these technologies, and by lack of basic knowledge to link genetic changes directly to symptoms. The consequence is that clinical diagnoses remain impossible except for a small number of children.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001868","title":"Recent genetic history of Denmark","description":"The \"Where Are You From?\" project explores the extent to which recent and more distant historical events left their mark on the genetic structure of the current Danish population. The project's ultimate goal is to gain insights into the historical complexity of Denmark from the genetic perspective. To this goal, a data set consisting of approximately 800 high school students from across Denmark was used to run an extensive genetic analysis.","abstract":"The \"Where Are You From?\" project explores the extent to which recent and more distant historical events left their mark on the genetic structure of the current Danish population. The project's ultimate goal is to gain insights into the historical complexity of Denmark from the genetic perspective. To this goal, a data set consisting of approximately 800 high school students from across Denmark was used to run an extensive genetic analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-06-08T14:50:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001869","title":"Single_cell_RNA_seq_and_bisulfite_seq_at_various_stares_of_HiPSCs_differentiating_toward_definitive_endoderm_derived_lineages","description":"When comparing the differentiation capacities of pluripotent stem cell lines that have different\ngenetic backgrounds, batch to batch experimental variablility poses a significant challenge,\nespecially when trying to identify smaller effects. One way to address this issue is to\ndifferentiate several different lines in the same culture dish, thereby elimating experimental\nvariation. In addition, it allows researchers to analyze many more lines with less experiments.\nParallel single cell RNA-Seq and bisulfite sequencing exploits that individual cells are tagged and hence each cell canbe reliably assigned to the donor of origin based on the genetic variants it contains. In addition, analyzing the genetic signature of single cells within a differentiating population can reveal differentation stages that are not easily detected in bulk RNAseq data. Studying the transcriptome (RNA-seq) and DNA methylation (bisulfite-seq) from the same cell allows detailed comparison of expression and epigenetic effects.","abstract":"When comparing the differentiation capacities of pluripotent stem cell lines that have different genetic backgrounds, batch to batch experimental variablility poses a significant challenge, especially when trying to identify smaller effects. One way to address this issue is to differentiate several different lines in the same culture dish, thereby elimating experimental variation. In addition, it allows researchers to analyze many more lines with less experiments. Parallel single cell RNA-Seq and bisulfite sequencing exploits that individual cells are tagged and hence each cell canbe reliably assigned to the donor of origin based on the genetic variants it contains. In addition, analyzing the genetic signature of single cells within a differentiating population can reveal differentation stages that are not easily detected in bulk RNAseq data. Studying the transcriptome (RNA-seq) and DNA methylation (bisulfite-seq) from the same cell allows detailed comparison of expression and epigenetic effects.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001870","title":"CD4+ T cell subsets stratified by complement receptor type 2 (CR2) expression","description":"FACS-sorted CR2+ and CR2- naive and memory CD4+ T cells from healthy donors, plus  CR2+ naive CD4+ T cells activated using CD3/CD28 beads, were analyzed ex-vivo. Exome-enriched RNA sequencing was carried out for all subsets.","abstract":"FACS-sorted CR2+ and CR2- naive and memory CD4+ T cells from healthy donors, plus  CR2+ naive CD4+ T cells activated using CD3/CD28 beads, were analyzed ex-vivo. Exome-enriched RNA sequencing was carried out for all subsets.","study_type":"Other","pubmed_ids":[28814669],"external_links":null,"is_released":true,"released_date":"2016-06-10T15:03:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001871","title":"Multi-omics analysis of primary glioblastoma cell-lines shows recapitulation of pivotal molecular features of parental tumors","description":"Glioblastoma (GBM) is the deadliest primary brain cancer in adults. Emerging innovative therapies hold promise for personalized cancer treatment. Improving therapeutic options depends on research relying on relevant preclinical models. In this line we have established in the setting of the GlioTeX project (GBM and experimental therapeutics), a GBM-patient derived cell line library (GBM-PDCL). Multi-OMIC approach was used to determine the molecular landscape of PDCL and the extent to which they represent GBM tumors.","abstract":"Glioblastoma (GBM) is the deadliest primary brain cancer in adults. Emerging innovative therapies hold promise for personalized cancer treatment. Improving therapeutic options depends on research relying on relevant preclinical models. In this line we have established in the setting of the GlioTeX project (GBM and experimental therapeutics), a GBM-patient derived cell line library (GBM-PDCL). Multi-OMIC approach was used to determine the molecular landscape of PDCL and the extent to which they represent GBM tumors.","study_type":"Other","pubmed_ids":[27571888],"external_links":null,"is_released":true,"released_date":"2016-06-13T00:38:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001872","title":"RNA sequencing data from visceral and abdominal subcutaneous adipose tissue from morbidly obese women with normal glucose tolerance or type 2 diabetes","description":"The study group consisted of 17 obese women with normal glucose tolerance and 15 obese women with T2DM. Adipose tissue specimens were taken from the epigastric region of the abdominal wall (SAT) and from the major omentum (VAT). RNA was isolated and RNA sequencing was used to analyse the transcriptome. Dharuri H et al, Diabetologia. 2014;57(11):2384-92.","abstract":"The study group consisted of 17 obese women with normal glucose tolerance and 15 obese women with T2DM. Adipose tissue specimens were taken from the epigastric region of the abdominal wall (SAT) and from the major omentum (VAT). RNA was isolated and RNA sequencing was used to analyse the transcriptome. Dharuri H et al, Diabetologia. 2014;57(11):2384-92.","study_type":"Other","pubmed_ids":[25099943],"external_links":null,"is_released":true,"released_date":"2016-06-13T10:34:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001873","title":"Transcriptome_analysis_of_anaplastic_meningiomas","description":"Transcriptome of anaplastic meingiomas","abstract":"Detection of gene fusions and deferentially expressed genes in anaplastic meingiomas.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-06-14T11:04:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001874","title":"Mutant_clone_mapping_in_normal_oesophagus","description":"We will use targeted exome sequencing to examine normal appearing epithelium and whole exome and whole genome sequencing of microdissected clones identified by immunostaining\n\nSome of the samples will be of low DNA concentration and therefore may require extra rounds of amplification during library prep.","abstract":"We aim to assess the burden of mutant clones in normal human oesophagus, both of known driver oncogenic mutations and of mutants that drive clonal expansion but are not associated with cancer.  This will give insight into the earliest stages of cancer evolution.  As a comparator we will also examine abdominal skin from the same patient.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-06-14T11:29:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001875","title":"Variation in the Glucose Transporter gene SLC2A2 is associated with glycaemic response to metformin","description":"Metformin is the first-line antidiabetic drug with over 100 million users worldwide, yet its mechanism of action remains unclear1. Here the Metformin Genetics (MetGen) Consortium reports a three-stage genome wide association study (GWAS), consisting of 13,123 participants of different ancestries. The C-allele of rs8192675 in the intron of SLC2A2, which encodes the facilitated glucose transporter GLUT2, was associated with a 0.17% (p=6.6x10-14) greater metformin induced HbA1c reduction in 10,577 participants of European ancestry. rs8192675 is the top cis-eQTL for SLC2A2 in 1,226 human liver samples, suggesting a key role for hepatic GLUT2 in regulation of metformin action. In obese individuals C-allele homozygotes at rs8192675 had a 0.33% (3.6mmol/mol) greater absolute HbA1c reduction than T-allele homozygotes.This is about half the effect seen with the addition of a DPP-4 inhibitor, and equates to a dose difference of 550mg of metformin, suggesting rs8192675 as a potential biomarker for stratified medicine.","abstract":"Metformin is the first-line antidiabetic drug with over 100 million users worldwide, yet its mechanism of action remains unclear1. Here the Metformin Genetics (MetGen) Consortium reports a three-stage genome wide association study (GWAS), consisting of 13,123 participants of different ancestries. The C-allele of rs8192675 in the intron of SLC2A2, which encodes the facilitated glucose transporter GLUT2, was associated with a 0.17% (p=6.6x10-14) greater metformin induced HbA1c reduction in 10,577 participants of European ancestry. rs8192675 is the top cis-eQTL for SLC2A2 in 1,226 human liver samples, suggesting a key role for hepatic GLUT2 in regulation of metformin action. In obese individuals C-allele homozygotes at rs8192675 had a 0.33% (3.6mmol/mol) greater absolute HbA1c reduction than T-allele homozygotes.This is about half the effect seen with the addition of a DPP-4 inhibitor, and equates to a dose difference of 550mg of metformin, suggesting rs8192675 as a potential biomarker for stratified medicine.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-06-16T16:18:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001876","title":"Exome and RNA sequencing of relapsed TCF3-PBX1 t(1;19) acute lymphoblastic leukemia","description":"TCF3-PBX1 (E2A-PBX1) is a recurrent gene fusion in B-cell precursor lymphoblastic leukemia (BCP-ALL), which is caused by the translocation t(1;19)(q23;p13). TCF3-PBX1 BCP-ALL patients typically benefit from chemotherapy; however, many relapse and subsequently develop resistant disease with few effective treatment options. Mechanisms driving disease progression and therapy resistance have not been studied in TCF3-PBX1 BCP-ALL. Here, we aimed to identify novel treatment options for TCF3-PBX1 BCP-ALL by profiling leukemia cells from a relapsed patient, and determine molecular mechanisms underlying disease pathogenesis and progression. By drug sensitivity testing of leukemic blasts from the index patient, control samples and TCF3-PBX1 positive and negative BCP-ALL cell lines, we identified the phosphatidylinositide 3-kinase delta (p110δ) inhibitor idelalisib as an effective treatment for TCF3-PBX1 BCP-ALL. This was further supported by evidence showing TCF3-PBX1 directly regulates expression of PIK3CD, the gene encoding p110δ. Other somatic mutations to TP53 and MTOR, as well as aberrant expression of CXCR4, may influence additional drug sensitivities specific to the index patient and accompanied progression of the disease. Our results suggest that idelalisib is a promising treatment option for patients with TCF3-PBX1 BCP-ALL while other drugs could be useful depending on the genetic context of individual patients.","abstract":"TCF3-PBX1 (E2A-PBX1) is a recurrent gene fusion in B-cell precursor lymphoblastic leukemia (BCP-ALL), which is caused by the translocation t(1;19)(q23;p13). TCF3-PBX1 BCP-ALL patients typically benefit from chemotherapy; however, many relapse and subsequently develop resistant disease with few effective treatment options. Mechanisms driving disease progression and therapy resistance have not been studied in TCF3-PBX1 BCP-ALL. Here, we aimed to identify novel treatment options for TCF3-PBX1 BCP-ALL by profiling leukemia cells from a relapsed patient, and determine molecular mechanisms underlying disease pathogenesis and progression. By drug sensitivity testing of leukemic blasts from the index patient, control samples and TCF3-PBX1 positive and negative BCP-ALL cell lines, we identified the phosphatidylinositide 3-kinase delta (p110δ) inhibitor idelalisib as an effective treatment for TCF3-PBX1 BCP-ALL. This was further supported by evidence showing TCF3-PBX1 directly regulates expression of PIK3CD, the gene encoding p110δ. Other somatic mutations to TP53 and MTOR, as well as aberrant expression of CXCR4, may influence additional drug sensitivities specific to the index patient and accompanied progression of the disease. Our results suggest that idelalisib is a promising treatment option for patients with TCF3-PBX1 BCP-ALL while other drugs could be useful depending on the genetic context of individual patients.","study_type":"Other","pubmed_ids":[27461063],"external_links":null,"is_released":true,"released_date":"2016-06-19T17:25:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001877","title":"OCCAMS_Oesophageal_Cancer_Organoids_RNAseq","description":"***THIS DATA CAN ONLY BE USED FOR NON-COMMERCIAL CANCER RESEARCH*** \nSequencing of organoid cell lines derived from oesophageal tumour sections taken from patients diagnosed with primary oesophageal cancer who underwent tumour resection surgery","abstract":"***THIS DATA CAN ONLY BE USED FOR NON-COMMERCIAL CANCER RESEARCH*** \nSequencing of organoid cell lines derived from oesophageal tumour sections taken from patients diagnosed with primary oesophageal cancer who underwent tumour resection surgery","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001878","title":"Non-Mendalian inheritance of extrachromosal DNA elements can drive disease evolution in glioblastoma","description":"Genomic heterogeneity of glioblastoma (GBM) is suspected to contribute to the poor response to therapy of this disease. We compared molecular characteristics between primary GBM, neurospheres and orthotopic xenograft models derived from the same parental tumor. Driver alterations were in majority propagated from tumor to model systems. Extrachromosomal amplifications of MET, a proto-oncogene coding for a receptor tyrosine kinase, were detected in three primary GBM, largely discarded in neurospheres cultures, but resurfaced in xenografts. The clonal dynamics inferred by somatic single nucleotide variants (sSNVs) in MET-amplified samples diverged from the pattern delineated by the MET amplification event suggesting that the MET event and sSNVs were inherited in different manners. Our analysis shows that extrachromosomal elements are able to drive tumor progression.","abstract":"Genomic heterogeneity of glioblastoma (GBM) is suspected to contribute to the poor response to therapy of this disease. We compared molecular characteristics between primary GBM, neurospheres and orthotopic xenograft models derived from the same parental tumor. Driver alterations were in majority propagated from tumor to model systems. Extrachromosomal amplifications of MET, a proto-oncogene coding for a receptor tyrosine kinase, were detected in three primary GBM, largely discarded in neurospheres cultures, but resurfaced in xenografts. The clonal dynamics inferred by somatic single nucleotide variants (sSNVs) in MET-amplified samples diverged from the pattern delineated by the MET amplification event suggesting that the MET event and sSNVs were inherited in different manners. Our analysis shows that extrachromosomal elements are able to drive tumor progression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-06-21T15:27:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001879","title":"EATL-II STUDY","description":"Enteropathy-associated T-cell lymphoma (EATL), a rare and aggressive intestinal malignancy of intraepithelial T lymphocytes, comprises two disease variants (EATL-I and EATL-II) differing in clinical characteristics and pathological features. Here we report findings derived from whole exome sequencing of 15 EATL-II tumor-normal tissue pairs. The tumor suppressor gene SETD2 encoding a non-redundant H3K36-specific trimethyltransferase is altered in 14/15 cases (93%), mainly by loss-of-function mutations and/or loss of the corresponding locus (3p21.31). These alterations consistently correlate with defective H3K36 trimethylation. The JAK/STAT pathway comprises recurrent STAT5B (60%), JAK3 (46%) and SH2B3 (20%) mutations, including a STAT5B V712E activating variant. Additionally, frequent mutations in TP53, BRAF and KRAS are observed. Conversely, in EATL-I, no SETD2, STAT5B or JAK3 mutations are found, and H3K36 trimethylation is preserved. This study describes SETD2 inactivation as EATL-II molecular hallmark, supports EATL-I and -II being two distinct entities, and defines potential new targets for therapeutic intervention.","abstract":"Enteropathy-associated T-cell lymphoma (EATL), a rare and aggressive intestinal malignancy of intraepithelial T lymphocytes, comprises two disease variants (EATL-I and EATL-II) differing in clinical characteristics and pathological features. Here we report findings derived from whole exome sequencing of 15 EATL-II tumor-normal tissue pairs. The tumor suppressor gene SETD2 encoding a non-redundant H3K36-specific trimethyltransferase is altered in 14/15 cases (93%), mainly by loss-of-function mutations and/or loss of the corresponding locus (3p21.31). These alterations consistently correlate with defective H3K36 trimethylation. The JAK/STAT pathway comprises recurrent STAT5B (60%), JAK3 (46%) and SH2B3 (20%) mutations, including a STAT5B V712E activating variant. Additionally, frequent mutations in TP53, BRAF and KRAS are observed. Conversely, in EATL-I, no SETD2, STAT5B or JAK3 mutations are found, and H3K36 trimethylation is preserved. This study describes SETD2 inactivation as EATL-II molecular hallmark, supports EATL-I and -II being two distinct entities, and defines potential new targets for therapeutic intervention.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-06-22T16:58:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001880","title":"Spatiotemporal genomic architecture informs precision oncology in glioblsatoma","description":"We characterized genomic and expression profiles across 127 multi-sector or longitudinal specimens from 52 glioma patients. We showed that, while samples from nearby geographical location shared similar genomic alterations (clonal or subclonal) and expression signatures, multifocal tumors were seeded from individual clones.","abstract":"We characterized genomic and expression profiles across 127 multi-sector or longitudinal specimens from 52 glioma patients. We showed that, while samples from nearby geographical location shared similar genomic alterations (clonal or subclonal) and expression signatures, multifocal tumors were seeded from individual clones.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-06-23T09:58:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001881","title":"Investigating genetic susceptibility to rheumatic heart disease in Oceania","description":"This case-control study investigated susceptibility to rheumatic heart disease in over 3,000 individuals recruited across eight Oceanian countries. Cases were patients with rheumatic heart disease and controls were members of the general population.  In addition to the Illumina HumanCore-24 BeadChip genotyping, a subset of 128 samples were analysed using the higher density Illumina HumanOmniExpressExome BeadChip of which 64 were also analysed using low coverage sequencing with the Illumina HiSeq 4000 platform.","abstract":"This case-control study investigated susceptibility to rheumatic heart disease in over 3,000 individuals recruited across eight Oceanian countries. Cases were patients with rheumatic heart disease and controls were members of the general population.  In addition to the Illumina HumanCore-24 BeadChip genotyping, a subset of 128 samples were analysed using the higher density Illumina HumanOmniExpressExome BeadChip of which 64 were also analysed using low coverage sequencing with the Illumina HiSeq 4000 platform.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-06-23T10:56:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001882","title":"Second generation noninvasive fetal genome analysis reveals de novo mutations, single-base parental inheritance, and preferred DNA ends","description":"Second generation noninvasive fetal genome analysis reveals de novo mutations, single-base parental inheritance, and preferred DNA ends","abstract":"Second generation noninvasive fetal genome analysis reveals de novo mutations, single-base parental inheritance, and preferred DNA ends","study_type":"Other","pubmed_ids":[27799561],"external_links":null,"is_released":true,"released_date":"2016-06-24T06:28:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001883","title":"Resolving_the_Genetic_Architecture_of_Aseptic_Loosening_After_Total_Hip_Replacement","description":"This is a genome-wide association scan of aseptic loosening after total hip replacement in a Norwegian population.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"12% of total hip arthroplasty prostheses (THA) fail within 10 years, and require revision surgery. Aseptic loosening,the risk of which varies between individuals, accounts for 62% of these failures. Here we aim to identify key genetic risk factors and pathways contributing to aseptic loosening.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-06-27T08:55:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001884","title":"Oral Metagenomics of Human Samples","description":"Oral microbiome of human being is essential to maintain health. Hence a study of 111 subjects who attended the NGBT 2015 conference was performed. The oral microbiome is comprised over several hundreds of prevalent taxa at species level.","abstract":"Oral microbiome of human being is essential to maintain health. Hence a study of 111 subjects who attended the NGBT 2015 conference was performed. The oral microbiome is comprised over several hundreds of prevalent taxa at species level.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001885","title":"Human oral metagenomics of 111 subjetcs","description":"Oral microbiome of human being is essential to maintain health. Hence a study of 111 subjects who attended the NGBT 2015 conference was performed. The oral microbiome is comprised over several hundreds of prevalent taxa at species level.","abstract":"Oral microbiome of human being is essential to maintain health. Hence a study of 111 subjects who attended the NGBT 2015 conference was performed. The oral microbiome is comprised over several hundreds of prevalent taxa at species level.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001886","title":"We performed an integrative analysis to determine genomic aberrations common to  sporadic schwannomas.","description":"Schwannomas are common peripheral nerve sheath tumors that can cause significant debilitating morbidities. We performed an integrative analysis to determine genomic aberrations common to  sporadic schwannomas. Exome sequence analysis with validation by targeted DNA-sequencing of 125 samples uncovered, in addition to expected NF2 disruption additional recurrent mutations. RNA sequencing identified a recurrent in-frame SH3PXD2A-HTRA1 fusion in 12/125 (10%) cases, and genomic analysis demonstrated the mechanism as resulting from a balanced 19Mb chromosomal inversion on chromosome 10q.","abstract":"Schwannomas are common peripheral nerve sheath tumors that can cause significant debilitating morbidities. We performed an integrative analysis to determine genomic aberrations common to  sporadic schwannomas. Exome sequence analysis with validation by targeted DNA-sequencing of 125 samples uncovered, in addition to expected NF2 disruption additional recurrent mutations. RNA sequencing identified a recurrent in-frame SH3PXD2A-HTRA1 fusion in 12/125 (10%) cases, and genomic analysis demonstrated the mechanism as resulting from a balanced 19Mb chromosomal inversion on chromosome 10q.","study_type":"Other","pubmed_ids":[27723760],"external_links":null,"is_released":true,"released_date":"2016-06-28T20:33:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001887","title":"Mutational_Signatures_in_Neural_Differentiation","description":"To characterise mutational signatures in neural lineages during differentiation from iPS cells to neural cells","abstract":"To characterise mutational signatures in neural lineages during differentiation from iPS cells to neural cells","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001888","title":"ELGH_genotyping","description":"East London Genes and Health (ELGH) is a cohort of healthy British South Asians being recruited by David van Heel, Richard Trembath and colleagues, with consent for recall. We are sequencing ELGH samples as the main cohort for the Autozygosity project, to find rare homozygous functional variants in healthy humans. This application is to genotype a random sample of 480 ELGH recruits on the Illumina Multi-ethnic Global 8 array.  \nCurrently we are only sequencing the ~20% of recruits who report that their parents are related. Amongst the first 535 samples, mean autozygosity is 4.5%, and 43% of samples have &gt;5% autozygosity, similar to that expected from first cousin marriage (6.25%). Recently we analysed genotype data from the Born in Bradford (BiB) cohort, which formed the core of our previous autozygosity sequencing (Narasimhan et al., Science, 2016), and discovered that in the BiB people who had not reported parental relatedness, another 22% (443/2049) actually had over 5% autozygosity. We therefore want to characterise more fully the distribution of autozygosity amongst the ELGH participants. So far, ~12,000 have been collected, but we estimate that 480 will give us a good assessment of the distribution of autozygosity amongst people in the cohort that we can correlate with information provided at recruitment on self- reported parental relatedness, ethnicity, age etc. This will both allow us to optimise our sequencing strategy, and also act as preliminary data to support applications for funds to genotype or low-coverage sequence (RD's preferred option) everyone in the cohort. We will also include some people we are sequencing anyway, which will allow us to evaluate imputation performance on exome regions. We have chosen the Multi-ethnic Global 8 to give as full information as reasonably possible.   \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"East London Genes and Health (ELGH) is a cohort of healthy British South Asians being recruited by David van Heel, Richard Trembath and colleagues, with consent for recall. We are sequencing ELGH samples as the main cohort for the Autozygosity project, to find rare homozygous functional variants in healthy humans. This application is to genotype a random sample of 480 ELGH recruits on the Illumina Multi-ethnic Global 8 array.   \nCurrently we are only sequencing the ~20% of recruits who report that their parents are related. Amongst the first 535 samples, mean autozygosity is 4.5%, and 43% of samples have &gt;5% autozygosity, similar to that expected from first cousin marriage (6.25%). Recently we analysed genotype data from the Born in Bradford (BiB) cohort, which formed the core of our previous autozygosity sequencing (Narasimhan et al., Science, 2016), and discovered that in the BiB people who had not reported parental relatedness, another 22% (443/2049) actually had over 5% autozygosity. We therefore want to characterise more fully the distribution of autozygosity amongst the ELGH participants. So far, ~12,000 have been collected, but we estimate that 480 will give us a good assessment of the distribution of autozygosity amongst people in the cohort that we can correlate with information provided at recruitment on self- reported parental relatedness, ethnicity, age etc. This will both allow us to optimise our sequencing strategy, and also act as preliminary data to support applications for funds to genotype or low-coverage sequence (RD's preferred option) everyone in the cohort. We will also include some people we are sequencing anyway, which will allow us to evaluate imputation performance on exome regions. We have chosen the Multi-ethnic Global 8 to give as full information as reasonably possible.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001889","title":"Whole exome sequencing data of germline and two independent primary leukemias of five patients","description":"The contribution of genetic predisposing factors to the development of pediatric acute lymphoblastic leukemia (ALL), the most frequently diagnosed cancer in childhood, has not been fully elucidated. Children presenting with multiple de novo leukemias are more likely to suffer from genetic predisposition. Here, we selected five of these patients and analyzed the mutational spectrum of normal and malignant tissues. In two patients, we identified germline mutations in TYK2, a member of the JAK tyrosine kinase family. These mutations were located in two adjacent codons of the pseudokinase domain (p.Pro760Leu and p.Gly761Val). In silico modeling revealed that both mutations affect the conformation of this auto-regulatory domain. Consistent with this notion, both germline mutations promote TYK2 autophosphorylation and activate downstream STAT family members, which could be blocked with the JAK kinase inhibitor I. These data indicate that germline activating TYK2 mutations predispose to the development of ALL.","abstract":"The contribution of genetic predisposing factors to the development of pediatric acute lymphoblastic leukemia (ALL), the most frequently diagnosed cancer in childhood, has not been fully elucidated. Children presenting with multiple de novo leukemias are more likely to suffer from genetic predisposition. Here, we selected five of these patients and analyzed the mutational spectrum of normal and malignant tissues. In two patients, we identified germline mutations in TYK2, a member of the JAK tyrosine kinase family. These mutations were located in two adjacent codons of the pseudokinase domain (p.Pro760Leu and p.Gly761Val). In silico modeling revealed that both mutations affect the conformation of this auto-regulatory domain. Consistent with this notion, both germline mutations promote TYK2 autophosphorylation and activate downstream STAT family members, which could be blocked with the JAK kinase inhibitor I. These data indicate that germline activating TYK2 mutations predispose to the development of ALL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-06-30T15:50:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001890","title":"Lineage-specific genome architecture links disease variants to target genes","description":"Long-range interactions between DNA regulatory elements and their target genes play major roles in gene regulation. The vast majority of interactions are uncharted, constituting a major missing link in understanding genome control. Here we use promoter capture Hi-C to identify interacting regions of 31,253 promoters in 17 human primary haematopoietic cell types. We show that long-range promoter interactions are highly cell-type specific, preferentially linking active promoters and enhancers. Patterns of promoter interactions reflect cell lineage relationships of the hematopoietic tree, consistent with dynamic remodeling of nuclear architecture during differentiation. Interacting regions are enriched for expression quantitative trait loci with effects on their interacting target genes.  We exploit this rich resource of interactome maps to connect non-coding disease variants to their target promoters, identifying thousands of new disease-candidate genes, and implicating a number of gene pathways in disease susceptibility. Our results demonstrate the power of promoter interactomes from primary cells to reveal insights into genomic regulatory mechanisms underlying common diseases.","abstract":"Long-range interactions between DNA regulatory elements and their target genes play major roles in gene regulation. The vast majority of interactions are uncharted, constituting a major missing link in understanding genome control. Here we use promoter capture Hi-C to identify interacting regions of 31,253 promoters in 17 human primary haematopoietic cell types. We show that long-range promoter interactions are highly cell-type specific, preferentially linking active promoters and enhancers. Patterns of promoter interactions reflect cell lineage relationships of the hematopoietic tree, consistent with dynamic remodeling of nuclear architecture during differentiation. Interacting regions are enriched for expression quantitative trait loci with effects on their interacting target genes.  We exploit this rich resource of interactome maps to connect non-coding disease variants to their target promoters, identifying thousands of new disease-candidate genes, and implicating a number of gene pathways in disease susceptibility. Our results demonstrate the power of promoter interactomes from primary cells to reveal insights into genomic regulatory mechanisms underlying common diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001891","title":"ORCADES_15x","description":"15x whole genome sequencing in samples from the isolated population of Orkney","abstract":"15x whole genome sequencing in samples from the isolated population of Orkney","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-07-04T17:17:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001892","title":"Inactivation of TGFβ receptors in stem cells drives cutaneous squamous cell carcinoma - 30 whole exomes","description":"Melanoma patients treated with oncogenic BRAF inhibitors can develop cutaneous squamous cell carcinoma (cSCC) within weeks of treatment, driven by paradoxical RAS/RAF/MAPK pathway activation. Here, we identify frequent TGFBR1 and TGFBR2 mutations in human vemurafenib-induced skin lesions and in sporadic cSCC. Functional analysis reveals these mutations ablate canonical TGFβ Smad signaling which is localised to bulge stem cells in both normal human and murine skin. MAPK pathway hyperactivation (through BrafV600E or KrasG12D knockin) and TGFβ signaling ablation (through Tgfbr1 deletion) in LGR5+ve stem cells enables rapid cSCC development in the mouse. Mutation of Tp53 (which is commonly mutated in sporadic cSCC) coupled with Tgfbr1 deletion in LGR5+ve cells also results in cSCC development. These findings indicate that LGR5+ve stem cells can act as cells of origin for cSCC and that RAS/RAF/MAPK pathway hyperactivation or Tp53 mutation, coupled with loss of TGFβ signaling, are driving events of skin tumorigenesis.","abstract":"Melanoma patients treated with oncogenic BRAF inhibitors can develop cutaneous squamous cell carcinoma (cSCC) within weeks of treatment, driven by paradoxical RAS/RAF/MAPK pathway activation. Here, we identify frequent TGFBR1 and TGFBR2 mutations in human vemurafenib-induced skin lesions and in sporadic cSCC. Functional analysis reveals these mutations ablate canonical TGFβ Smad signaling which is localised to bulge stem cells in both normal human and murine skin. MAPK pathway hyperactivation (through BrafV600E or KrasG12D knockin) and TGFβ signaling ablation (through Tgfbr1 deletion) in LGR5+ve stem cells enables rapid cSCC development in the mouse. Mutation of Tp53 (which is commonly mutated in sporadic cSCC) coupled with Tgfbr1 deletion in LGR5+ve cells also results in cSCC development. These findings indicate that LGR5+ve stem cells can act as cells of origin for cSCC and that RAS/RAF/MAPK pathway hyperactivation or Tp53 mutation, coupled with loss of TGFβ signaling, are driving events of skin tumorigenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-07-04T23:12:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001893","title":"The molecular landscape of colorectal cancer reveals genetic mutations.","description":"We performed whole-exome sequencing of tumor samples and adjacent normal mucosae from 46 patients to characterize the genetic alterations in China.","abstract":"We performed whole-exome sequencing of tumor samples and adjacent normal mucosae from 46 patients to characterize the genetic alterations in China.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-07-06T07:41:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001894","title":"Human_immunity_against_herpesviridae","description":"Lymphocytes from CMV seropositive donors were sorted and single cells were processed using smartseq2 protocol. \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This study aims to better understandthe immune response against herpesviridae, specifically CMV. We aim to acquire a better understanding on the immunity against these latent viruses in healthy individuals.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001895","title":"Genetic control of the transcriptomic response of monocytes to bacterial and viral stimuli assessed by RNA-seq in Africans and Europeans","description":"Humans differ in the outcome that follows exposure to life-threatening pathogens, yet the extent of population differences in immune responses, and their genetic and evolutionary determinants, remain undefined. Here, we characterized, using RNA-sequencing, the transcriptional response of primary monocytes from Africans and Europeans to bacterial and viral stimuli - ligands activating Toll-like receptors pathways (TLR1/2, TLR4 and TLR7/8) and influenza virus - and mapped expression quantitative trait loci (eQTL). We identify multiple cis- and trans-eQTL that contribute to the marked differences in immune responses detected within and between populations, including a TLR1 master regulator that decreases expression of pro-inflammatory genes in Europeans only. We show that regulatory variants have been privileged targets of natural selection, uncovering evolutionarily advantageous mechanisms, such as attenuated inflammation. Finally, we demonstrate that admixture with Neandertals introduced regulatory variants into European genomes, affecting preferentially responses to viral challenges, and identify archaic haplotypes that contributed to population genetic adaptation.","abstract":"Humans differ in the outcome that follows exposure to life-threatening pathogens, yet the extent of population differences in immune responses, and their genetic and evolutionary determinants, remain undefined. Here, we characterized, using RNA-sequencing, the transcriptional response of primary monocytes from Africans and Europeans to bacterial and viral stimuli - ligands activating Toll-like receptors pathways (TLR1/2, TLR4 and TLR7/8) and influenza virus - and mapped expression quantitative trait loci (eQTL). We identify multiple cis- and trans-eQTL that contribute to the marked differences in immune responses detected within and between populations, including a TLR1 master regulator that decreases expression of pro-inflammatory genes in Europeans only. We show that regulatory variants have been privileged targets of natural selection, uncovering evolutionarily advantageous mechanisms, such as attenuated inflammation. Finally, we demonstrate that admixture with Neandertals introduced regulatory variants into European genomes, affecting preferentially responses to viral challenges, and identify archaic haplotypes that contributed to population genetic adaptation.","study_type":"Other","pubmed_ids":[27768888],"external_links":null,"is_released":true,"released_date":"2016-07-06T14:13:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001896","title":"Molecular dissection of germline chromothripsis in a developmental context","description":"Complex germline genomic rearrangements can affect many genes and regulatory elements, but the precise mechanisms that caused the phenotype of patients with such rearrangements are often unknown. To dissect the impact of germline chromothripsis in a relevant developmental context, we performed trio-based RNA expression analysis on blood cells,induced pluripotent stem (iPS) cells and iPS-cell derived neuronal cells from a patient with de novo germline chromothripsis and both healthy parents. In addition, we performed Hi-C on iPS cell-derived neural progenitors of the patient and the father to study the effects of the chromothripsis rearrangements on the architecture of the derivative\nchromosomes. We demonstrate that a combination of patient-derived iPS cell differentiation and trio-based molecular profiling is a powerful approach to improve the interpretation of pathogenic complex genomic rearrangements.","abstract":"Complex germline genomic rearrangements can affect many genes and regulatory elements, but the precise mechanisms that caused the phenotype of patients with such rearrangements are often unknown. To dissect the impact of germline chromothripsis in a relevant developmental context, we performed trio-based RNA expression analysis on blood cells,induced pluripotent stem (iPS) cells and iPS-cell derived neuronal cells from a patient with de novo germline chromothripsis and both healthy parents. In addition, we performed Hi-C on iPS cell-derived neural progenitors of the patient and the father to study the effects of the chromothripsis rearrangements on the architecture of the derivative\nchromosomes. We demonstrate that a combination of patient-derived iPS cell differentiation and trio-based molecular profiling is a powerful approach to improve the interpretation of pathogenic complex genomic rearrangements.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-07-07T12:14:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001897","title":"Integrated Molecular Profilting in Advanced Cancers Trial","description":"The present protocol seeks to provide molecular profiling data to the treating physician for patients with advanced breast, non-small cell lung, colorectal, genitourinary, pancreatobiliary gastrointestinal, upper aerodigestive tract, gynecological, melanoma, unknown primary, and rare carcinomas, as well as patients who are phase I trial candidates, in order to help identify which standard regimens or clinical trials of molecularly targeted therapies may be most appropriate for the individual patient.","abstract":"The present protocol seeks to provide molecular profiling data to the treating physician for patients with advanced breast, non-small cell lung, colorectal, genitourinary, pancreatobiliary gastrointestinal, upper aerodigestive tract, gynecological, melanoma, unknown primary, and rare carcinomas, as well as patients who are phase I trial candidates, in order to help identify which standard regimens or clinical trials of molecularly targeted therapies may be most appropriate for the individual patient.","study_type":"Other","pubmed_ids":[27626067],"external_links":null,"is_released":true,"released_date":"2016-07-07T19:46:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001898","title":"The Prediction and Prevention of Preeclampsia","description":"The Prediction and Prevention of Preeclampsia (PREDO) is a prospective birth cohort study of Finnish women who were pregnant between 2005 and 2010 and their children. The PREDO study cohort was set up to identify novel risk factors and biomarkers in pregnant women associated with the development of preeclampsia and intrauterine growth restriction (IUGR). Two groups of pregnant women were enrolled during the first trimester of their pregnancy: first, pregnant women with a known clinical risk factor status for preeclampsia and IUGR (N=1079; 969 of these women had at least one and 110 had none of the known risk factors for preeclampsia and IUGR), and second, pregnant women who volunteered to participate regardless of their risk factor status for preeclampsia and IUGR (N=3698). Both samples were monitored during pregnancy with four clinical visits and bi-weekly self-reports. The post-delivery follow-up has taken place at approximately 2 weeks, 6 months, and 3.5 years after the delivery. The most recent follow-up started in 2016 and is ongoing. In the high-risk sample, cord blood samples were collected and genome-wide genotyping has been conducted with Illumina OmniExpressExome 1.2 and genome-wide methylation status has been analysed with Illumina 450k HM array.","abstract":"The Prediction and Prevention of Preeclampsia (PREDO) is a prospective birth cohort study of Finnish women who were pregnant between 2005 and 2010 and their children. The PREDO study cohort was set up to identify novel risk factors and biomarkers in pregnant women associated with the development of preeclampsia and intrauterine growth restriction (IUGR). Two groups of pregnant women were enrolled during the first trimester of their pregnancy: first, pregnant women with a known clinical risk factor status for preeclampsia and IUGR (N=1079; 969 of these women had at least one and 110 had none of the known risk factors for preeclampsia and IUGR), and second, pregnant women who volunteered to participate regardless of their risk factor status for preeclampsia and IUGR (N=3698). Both samples were monitored during pregnancy with four clinical visits and bi-weekly self-reports. The post-delivery follow-up has taken place at approximately 2 weeks, 6 months, and 3.5 years after the delivery. The most recent follow-up started in 2016 and is ongoing. In the high-risk sample, cord blood samples were collected and genome-wide genotyping has been conducted with Illumina OmniExpressExome 1.2 and genome-wide methylation status has been analysed with Illumina 450k HM array.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-07-08T16:42:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001899","title":"Knee_OA_Functional_Genomics","description":"The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of knee  osteoarthritis that culminates in the need for total joint replacement (TJR). This study is a feasibility pilot that integrates functional genomics data from diseased and non-diseased tissues of OA patients who have undergone TJR. For each tissue, we characterised epigenetic marks (methylation), gene transcription (RNASeq) and expression (quantitative proteomics). We also generated genotype data on the HumanCoreExome array for each individual.","abstract":"The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of knee  osteoarthritis that culminates in the need for total joint replacement (TJR). This study is a feasibility pilot that integrates functional genomics data from diseased and non-diseased tissues of OA patients who have undergone TJR. For each tissue, we characterised epigenetic marks (methylation), gene transcription (RNASeq) and expression (quantitative proteomics). We also generated genotype data on the HumanCoreExome array for each individual.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-07-11T09:14:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001900","title":"Comparison of EGF and PDGF driven glioblastomas.","description":"Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor. Epidermal growth-factor (EGF) and platelet-derived growth-factor (PDGF) receptors are frequently amplified and/or possess gain-of-function mutations in these tumors. Despite years of research into tyrosine-kinase inhibitors, clinical trials have shown disappointing efficacy. One of the underlying reasons is intra-tumor heterogeneity. To assess the effect of intra-tumor heterogeneity on gene expression, we derived a general approach to map single-cell expression profiles to sequentially-acquired mutations identified from exome sequencing. Using 288 single cells, we constructed high-resolution phylogenies of EGF-driven and PDGF-driven GBMs, modeling transcriptional kinetics during tumor evolution. A deletion in a PDGF-receptor domain involved in dimerization correlated to an up-regulation of the PI3K/AKT pathway in a proneural GBM, and ectopic expression of this mutant PDGFRA in vitro enhanced proliferation and invasiveness. Descending the phylogenetic tree of the PDGFR-driven tumor corresponded to a progressive induction of an oligodendrocyte progenitor-like cell type that expresses growth and angiogenic factors. In contrast, phylogenetic analysis of an EGFR-amplified tumor showed a gradual up-regulation of pro-invasive genes.","abstract":"Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor. Epidermal growth-factor (EGF) and platelet-derived growth-factor (PDGF) receptors are frequently amplified and/or possess gain-of-function mutations in these tumors. Despite years of research into tyrosine-kinase inhibitors, clinical trials have shown disappointing efficacy. One of the underlying reasons is intra-tumor heterogeneity. To assess the effect of intra-tumor heterogeneity on gene expression, we derived a general approach to map single-cell expression profiles to sequentially-acquired mutations identified from exome sequencing. Using 288 single cells, we constructed high-resolution phylogenies of EGF-driven and PDGF-driven GBMs, modeling transcriptional kinetics during tumor evolution. A deletion in a PDGF-receptor domain involved in dimerization correlated to an up-regulation of the PI3K/AKT pathway in a proneural GBM, and ectopic expression of this mutant PDGFRA in vitro enhanced proliferation and invasiveness. Descending the phylogenetic tree of the PDGFR-driven tumor corresponded to a progressive induction of an oligodendrocyte progenitor-like cell type that expresses growth and angiogenic factors. In contrast, phylogenetic analysis of an EGFR-amplified tumor showed a gradual up-regulation of pro-invasive genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-07-11T18:25:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001901","title":"Whole Genome Sequencing of Gingivo-buccal Cancer: ICGC-India Project_YR03","description":"As a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India.   There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection.  Whole genome sequencing of paired DNA samples – isolated from the tumor tissue and from the blood of twenty five patients – have been performed to catalog germline and somatic mutations. Association between each observed genomic alteration and exposure to environmental risk factors is being explored.\tDetailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from blood and tumor tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai.  Whole genome sequencing is being performed at the National Institute of Biomedical Genomics, Kalyani. We have completed whole genome sequencing of paired blood and tumor DNA samples using Illumina HiSeq-2000 and 2500.","abstract":"As a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India.   There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection.  Whole genome sequencing of paired DNA samples – isolated from the tumor tissue and from the blood of twenty five patients – have been performed to catalog germline and somatic mutations. Association between each observed genomic alteration and exposure to environmental risk factors is being explored.\tDetailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from blood and tumor tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai.  Whole genome sequencing is being performed at the National Institute of Biomedical Genomics, Kalyani. We have completed whole genome sequencing of paired blood and tumor DNA samples using Illumina HiSeq-2000 and 2500.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-07-13T07:22:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001902","title":"Epigenomic_profiling_of_chromatin_related_developmental_disorders","description":"This study will look to identify characteristic DNA methylation signatures for specific chromatin-related developmental disorders in accessible tissues. It will  investigate whether similarity of DNA methylation signatures correlates with clinical phenotypes, e.g. severity, affected tissues, etc.  and explore whether we can use DNA methylation signatures to refine diagnostic interpretation of variants of uncertain significance, for example, an intronic de novo mutation, close to, but not within the 2bp canonical splice site of a gene with a characteristic methylation signature in an accessible tissue.                                                                                                                              This project is to apply the Illumina EPIC methylation array (successor to the 450K array, now discontinued) to 128 DNA samples, including ~5 patients for each of ~20 chromatin-related disorders, plus patients with variants of uncertain significance in those genes, plus age-matched negative controls: DDD patients with pathogenic de novo mutations in genes encoding brain-specific proteins, e.g.ion channels, synaptic proteins, that would not be expected to have a perturbed epigenome in whole blood.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"This study will look to identify characteristic DNA methylation signatures for specific chromatin-related developmental disorders in accessible tissues. It will  investigate whether similarity of DNA methylation signatures correlates with clinical phenotypes, e.g. severity, affected tissues, etc.  and explore whether we can use DNA methylation signatures to refine diagnostic interpretation of variants of uncertain significance, for example, an intronic de novo mutation, close to, but not within the 2bp canonical splice site of a gene with a characteristic methylation signature in an accessible tissue.\nThis project is to apply the Illumina EPIC methylation array (successor to the 450K array, now discontinued) to 128 DNA samples, including ~5 patients for each of ~20 chromatin-related disorders, plus patients with variants of uncertain significance in those genes, plus age-matched negative controls: DDD patients with pathogenic de novo mutations in genes encoding brain-specific proteins, e.g.ion channels, synaptic proteins, that would not be expected to have a perturbed epigenome in whole blood.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001903","title":"Identifying_germline_mutator_phenotypes_within_the_DDD_cohort_____","description":"This project is to perform WGS on 10 DDD trios with putative germline mutator phenotypes, including the top candidates for both genome-wide and clustered hypermutability phenotypes.","abstract":"Two different classes of somatic mutator phenotypes have been identified: genome-wide and clustered\nhypermutability. Germline mutator phenotypes have not been characterised in humans\nIn the DDD study we have exome sequenced 4,293 parent-offspring trios and identified high confidence de novo\nmutations, SNVs and indels. The distribution of numbers of de novo mutations per trio (exonic and intronic) follows\nan approximately Poisson distribution, with a mean of ~2.\nThis project is to perform WGS on 10 DDD trios with putative germline mutator phenotypes, including the top\ncandidates for both genome-wide and clustered hypermutability phenotypes.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001904","title":"Added in error","description":"Added in error","abstract":"Added in error","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001905","title":"2016_WGS_AML","description":"2016_WGS_AML","abstract":"2016_WGS_AML","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001906","title":"SNU_WGS_AML","description":"This study includes 10 paired samples of Korean AML paitients.10 AML tumor samples are paired with each normal(Saliva or BM derived) sequencing data.The results of this WGS study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.","abstract":"This study includes 10 paired samples of Korean AML paitients.10 AML tumor samples are paired with each normal(Saliva or BM derived) sequencing data.The results of this WGS study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-07-18T10:24:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001907","title":"Whole exome sequencing of MSS CRC tumours and cell lines as part of an investigation of effects of CIN","description":"Chromosomal instability (CIN) contributes to cancer evolution, intratumour heterogeneity and drug resistance. CIN is driven by an increase in the frequency of chromosome segregation errors and a tolerance phenotype that permits the propagation of aneuploid genomes. Through exome sequencing analysis of aneuploid and diploid colorectal cancers (CRC), we find frequent loss of heterozygosity and truncating mutations in BCL9L enriched in aneuploid tumours. Functional characterization revealed that BCL9L loss of function promoted tolerance of chromosome missgregation events, development of aneuploidy and increased tumourigenesis in xenograft models. We find that BCL9L dysfunction contributes to aneuploidy-tolerance in both TP53 wild type and mutant cells by reducing basal caspase-2 levels, preventing cleavage of BID and MDM2. Efforts to exploit aneuploidy tolerance mechanisms and the BCL9L/Caspase-2/BID axis may limit cancer diversity and evolution.","abstract":"Chromosomal instability (CIN) contributes to cancer evolution, intratumour heterogeneity and drug resistance. CIN is driven by an increase in the frequency of chromosome segregation errors and a tolerance phenotype that permits the propagation of aneuploid genomes. Through exome sequencing analysis of aneuploid and diploid colorectal cancers (CRC), we find frequent loss of heterozygosity and truncating mutations in BCL9L enriched in aneuploid tumours. Functional characterization revealed that BCL9L loss of function promoted tolerance of chromosome missgregation events, development of aneuploidy and increased tumourigenesis in xenograft models. We find that BCL9L dysfunction contributes to aneuploidy-tolerance in both TP53 wild type and mutant cells by reducing basal caspase-2 levels, preventing cleavage of BID and MDM2. Efforts to exploit aneuploidy tolerance mechanisms and the BCL9L/Caspase-2/BID axis may limit cancer diversity and evolution.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001908","title":"Breast Cancer - Very young women","description":"This project will focus on sequencing of breast cancer from young age cancer patients characterized by age at diagnosis under 35. Based on the incidence rate by Korean National Cancer Incidence Database, breast cancer is the most common solid tumors among young adults aged 15-34 excepting thyroid cancer (Cancer statistics in Korea (2012)). This project just started from the mid of 2015. National cancer center in Korea are collecting more than 100 tumor specimens from breast cancer patients aged 20-34. Genetic features of young patients will be investigated with somatic mutation pattern, structural variations, and canonical pathways.","abstract":"This project will focus on sequencing of breast cancer from young age cancer patients characterized by age at diagnosis under 35. Based on the incidence rate by Korean National Cancer Incidence Database, breast cancer is the most common solid tumors among young adults aged 15-34 excepting thyroid cancer (Cancer statistics in Korea (2012)). This project just started from the mid of 2015. National cancer center in Korea are collecting more than 100 tumor specimens from breast cancer patients aged 20-34. Genetic features of young patients will be investigated with somatic mutation pattern, structural variations, and canonical pathways.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-07-19T02:29:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001909","title":"Premalignant SOX2 overexpression in the fallopian tubes of ovarian cancer patients: Discovery and validation studies","description":"To identify early driver mutations in ovarian cancer cells, we used dense whole genome sequencing of micrometastases and microscopic residual disease collected at three time points from a single patient during treatment for high-grade serous ovarian cancer (HGSOC). Laser capture microdissection of tumour islets was performed on samples prior to chemotherapy, after three cycles of chemotherapy and at recurrence. Long frament read whole genome sequencing was performed and mutations were identified. To our knowledge, this is the first longitudinal study that attempts to investigate spatial and temporal micro-heterogeneity in cancer.","abstract":"To identify early driver mutations in ovarian cancer cells, we used dense whole genome sequencing of micrometastases and microscopic residual disease collected at three time points from a single patient during treatment for high-grade serous ovarian cancer (HGSOC). Laser capture microdissection of tumour islets was performed on samples prior to chemotherapy, after three cycles of chemotherapy and at recurrence. Long frament read whole genome sequencing was performed and mutations were identified. To our knowledge, this is the first longitudinal study that attempts to investigate spatial and temporal micro-heterogeneity in cancer.","study_type":"Other","pubmed_ids":[27492892],"external_links":null,"is_released":true,"released_date":"2016-07-20T22:03:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001910","title":"Novel regional age-associated DNA methylation changes within human common disease-associated loci","description":"Background: Advancing age progressively impacts on risk and severity of chronic disease. It also modifies the epigenome, with changes in DNA methylation, due to both random drift and variation within specific functional loci. Results: In a discovery set of 2,238 peripheral-blood genome-wide DNA methylomes (MeDIP-seq) aged 19-82 years, we identified 71 age-associated Differentially Methylated Regions (a-DMRs, p &lt; 1.85 x 10-8) within the Linkage Disequilibrium (LD) blocks of the NIH Catalogue of published GWAS SNPs. This included 52 novel regions, 29 within loci not covered by 450k or 27k Illumina array, and with marked enrichment for Poised Promoters and Enhancers across multiple cell types. In a replication set of 2,084 DNA methylomes, 95.7% of the a-DMRs showed the same direction of ageing effect, with 80.3% and 53.3% replicated to p &lt; 0.05 and p &lt; 1.85 x 10-8, respectively. Conclusion: By analysing the functionally enriched disease and trait-associated regions of the human genome, we identified novel epigenetic ageing changes, which could be useful biomarkers or provide mechanistic insights into age-related common diseases.","abstract":"Background: Advancing age progressively impacts on risk and severity of chronic disease. It also modifies the epigenome, with changes in DNA methylation, due to both random drift and variation within specific functional loci. Results: In a discovery set of 2,238 peripheral-blood genome-wide DNA methylomes (MeDIP-seq) aged 19-82 years, we identified 71 age-associated Differentially Methylated Regions (a-DMRs, p &lt; 1.85 x 10-8) within the Linkage Disequilibrium (LD) blocks of the NIH Catalogue of published GWAS SNPs. This included 52 novel regions, 29 within loci not covered by 450k or 27k Illumina array, and with marked enrichment for Poised Promoters and Enhancers across multiple cell types. In a replication set of 2,084 DNA methylomes, 95.7% of the a-DMRs showed the same direction of ageing effect, with 80.3% and 53.3% replicated to p &lt; 0.05 and p &lt; 1.85 x 10-8, respectively. Conclusion: By analysing the functionally enriched disease and trait-associated regions of the human genome, we identified novel epigenetic ageing changes, which could be useful biomarkers or provide mechanistic insights into age-related common diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-07-21T11:27:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001911","title":"Lineage-specific genome architecture links disease variants to target genes","description":"Long-range interactions between DNA regulatory elements and their target genes play major roles in gene regulation. The vast majority of interactions are uncharted, constituting a major missing link in understanding genome control. Here we use promoter capture Hi-C to identify interacting regions of 31,253 promoters in 17 human primary haematopoietic cell types. We show that long-range promoter interactions are highly cell-type specific, preferentially linking active promoters and enhancers. Patterns of promoter interactions reflect cell lineage relationships of the hematopoietic tree, consistent with dynamic remodeling of nuclear architecture during differentiation. Interacting regions are enriched for expression quantitative trait loci with effects on their interacting target genes.  We exploit this rich resource of interactome maps to connect non-coding disease variants to their target promoters, identifying thousands of new disease-candidate genes, and implicating a number of gene pathways in disease susceptibility. Our results demonstrate the power of promoter interactomes from primary cells to reveal insights into genomic regulatory mechanisms underlying common diseases.","abstract":"Long-range interactions between DNA regulatory elements and their target genes play major roles in gene regulation. The vast majority of interactions are uncharted, constituting a major missing link in understanding genome control. Here we use promoter capture Hi-C to identify interacting regions of 31,253 promoters in 17 human primary haematopoietic cell types. We show that long-range promoter interactions are highly cell-type specific, preferentially linking active promoters and enhancers. Patterns of promoter interactions reflect cell lineage relationships of the hematopoietic tree, consistent with dynamic remodeling of nuclear architecture during differentiation. Interacting regions are enriched for expression quantitative trait loci with effects on their interacting target genes.  We exploit this rich resource of interactome maps to connect non-coding disease variants to their target promoters, identifying thousands of new disease-candidate genes, and implicating a number of gene pathways in disease susceptibility. Our results demonstrate the power of promoter interactomes from primary cells to reveal insights into genomic regulatory mechanisms underlying common diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-07-22T11:54:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001912","title":"NeuroGenetics: mitochondrial, ataxias, spastic paraplegias and other rare neurogenetic conditions","description":"Inherited neurological diseases are clinically and genetically heterogeneous, and a molecular diagnosis is not possible in many patients. Having excluded common sporadic, inherited and metabolic causes, we used an unbiased whole exome sequencing approach in &gt;300 affected individuals, from randomly selected families. We defined the likely molecular diagnosis in approximately 60% of families. This revealed known and novel mutations in validated disease genes previously described in isolated families, which broadened the clinical phenotype of known disease genes. We have also reported several novel human disease genes.  The diagnostic yield was the same in both young and older-onset patients, including sporadic cases. We have demonstrated the impact of exome sequencing in a group of patients notoriously difficult to diagnose genetically. This has important implications for genetic counselling and diagnostic service provision.","abstract":"Inherited neurological diseases are clinically and genetically heterogeneous, and a molecular diagnosis is not possible in many patients. Having excluded common sporadic, inherited and metabolic causes, we used an unbiased whole exome sequencing approach in &gt;300 affected individuals, from randomly selected families. We defined the likely molecular diagnosis in approximately 60% of families. This revealed known and novel mutations in validated disease genes previously described in isolated families, which broadened the clinical phenotype of known disease genes. We have also reported several novel human disease genes.  The diagnostic yield was the same in both young and older-onset patients, including sporadic cases. We have demonstrated the impact of exome sequencing in a group of patients notoriously difficult to diagnose genetically. This has important implications for genetic counselling and diagnostic service provision.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001913","title":"Breast Cancer PDTX Encyclopaedia","description":"Molecular data from the collection of PDTX breast cancer models described in Bruna et al, 2016. Cell. It includes whole exome sequencing, shallow whole genome sequencing, expression arrays and reduced bisulfite representation sequencing (RRBS).","abstract":"Molecular data from the collection of PDTX breast cancer models described in Bruna et al, 2016. Cell. It includes whole exome sequencing, shallow whole genome sequencing, expression arrays and reduced bisulfite representation sequencing (RRBS).","study_type":"Other","pubmed_ids":[27641504],"external_links":null,"is_released":true,"released_date":"2016-07-24T13:15:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001914","title":"Maastricht IBS cohort MIBS","description":"Gut microbiome data of the Maastricht-IBS study","abstract":"Gut microbiome data of the Maastricht-IBS study","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-07-27T09:39:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001915","title":"Deciphering the aggressive nature of morphoeic basal cell carcinoma","description":"Morphoeic basal cell carcinoma (mBCC) has a high risk of local recurrence compared to the more indolent nodular subtype reflected by a different set of driver mutations including FLNB and HECTD4. Surrounding mBCC stroma is abnormal, containing mutations such as EPHA3. Hedgehog pathway over-expression is seen in both the tumour and stroma of morphoeic tissue with the latter potentially being partly responsible for its aggressive nature and risk of recurrence.","abstract":"Morphoeic basal cell carcinoma (mBCC) has a high risk of local recurrence compared to the more indolent nodular subtype reflected by a different set of driver mutations including FLNB and HECTD4. Surrounding mBCC stroma is abnormal, containing mutations such as EPHA3. Hedgehog pathway over-expression is seen in both the tumour and stroma of morphoeic tissue with the latter potentially being partly responsible for its aggressive nature and risk of recurrence.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001916","title":"Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas","description":"RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations in this enzyme have not been previously linked to any pathology in humans, a testament to its indispensable role in cell biology. Based on a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II1, are sufficient to hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors reveal dysregulation of key meningeal identity genes, including WNT6 and ZIC1/ZIC42,3. In addition to POLR2A, NF2, SMARCB1, TRAF7, KLF4, AKT1, PIK3CA and SMO4-8, we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features.","abstract":"RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations in this enzyme have not been previously linked to any pathology in humans, a testament to its indispensable role in cell biology. Based on a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II1, are sufficient to hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors reveal dysregulation of key meningeal identity genes, including WNT6 and ZIC1/ZIC42,3. In addition to POLR2A, NF2, SMARCB1, TRAF7, KLF4, AKT1, PIK3CA and SMO4-8, we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-07-29T15:51:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001917","title":"APCDR The African Genome Resource - A continent specific haplotype reference panel, transcriptomic resource and pan-continental data centre","description":"The African Genome Resource encompasses approximately 3000 whole genome sequences, 600 transcriptomes and an infrastructure for computation and capacity development in the form of a new informatics centre in Uganda. The three elements of the AGR are as follows: The African Diversity Reference Panel (ADRP). Whole genome DNAseq data at 4x-8x depth from approximately 3,000 Africans of 14 distinct ethnicities, which is the largest and most diverse set of haplotypes for the continent. More than 90 million SNPs of which many (more than 20 million) are novel and unique to the continent, highlighting the importance for the development of reference panels, SNP arrays and RNA sequencing resources specific to the continent. The African Transcriptomics Resource. RNAseq data from 6 different populations and the first large-scale resource to examine eQTLs within Africa, as well as diversity of splicing isoforms, and help identify novel transcripts, and exons across the genome. Such a resource will be invaluable for the interpretation of findings from large-scale GWAS being conducted in Africa, supporting initiatives such as the H3A consortium.  The Uganda Medical Informatics Centre (UMIC). A computational facility in Entebbe enabling local storage and handling of data from across the continent and supporting long term capacity building. Together, these three tangible resources will enable substantial advances in medical genetics in Africa. The large number of private variants across the continent and within the Khoesan population highlights the future need to further sequence indigenous populations across the continent.","abstract":"The African Genome Resource encompasses approximately 3000 whole genome sequences, 600 transcriptomes and an infrastructure for computation and capacity development in the form of a new informatics centre in Uganda. The three elements of the AGR are as follows: The African Diversity Reference Panel (ADRP). Whole genome DNAseq data at 4x-8x depth from approximately 3,000 Africans of 14 distinct ethnicities, which is the largest and most diverse set of haplotypes for the continent. More than 90 million SNPs of which many (more than 20 million) are novel and unique to the continent, highlighting the importance for the development of reference panels, SNP arrays and RNA sequencing resources specific to the continent. The African Transcriptomics Resource. RNAseq data from 6 different populations and the first large-scale resource to examine eQTLs within Africa, as well as diversity of splicing isoforms, and help identify novel transcripts, and exons across the genome. Such a resource will be invaluable for the interpretation of findings from large-scale GWAS being conducted in Africa, supporting initiatives such as the H3A consortium.  The Uganda Medical Informatics Centre (UMIC). A computational facility in Entebbe enabling local storage and handling of data from across the continent and supporting long term capacity building. Together, these three tangible resources will enable substantial advances in medical genetics in Africa. The large number of private variants across the continent and within the Khoesan population highlights the future need to further sequence indigenous populations across the continent.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001918","title":"RNA sequencing in blood samples of cluster headache patients","description":"Cluster headache is a relatively rare headache disorder, typically characterized by multiple daily, short-lasting attacks of excruciating, unilateral (peri-)orbital or temporal pain associated with autonomic symptoms and restlessness. To better understand the pathophysiology of cluster headache, we used RNA sequencing to identify differentially expressed genes and pathways in whole blood of patients with episodic (n = 19) or chronic (n = 20) cluster headache in comparison with headache-free controls (n = 20). Blood samples were subjected to globin reduction before sequencing.","abstract":"Cluster headache is a relatively rare headache disorder, typically characterized by multiple daily, short-lasting attacks of excruciating, unilateral (peri-)orbital or temporal pain associated with autonomic symptoms and restlessness. To better understand the pathophysiology of cluster headache, we used RNA sequencing to identify differentially expressed genes and pathways in whole blood of patients with episodic (n = 19) or chronic (n = 20) cluster headache in comparison with headache-free controls (n = 20). Blood samples were subjected to globin reduction before sequencing.","study_type":"Other","pubmed_ids":[28074859],"external_links":null,"is_released":true,"released_date":"2016-08-02T12:39:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001919","title":"RNA sequencing of whole blood from cluster headache patients and controls","description":"Cluster headache is a relatively rare headache disorder, typically characterized by multiple daily, short-lasting attacks of excruciating, unilateral (peri-)orbital or temporal pain associated with autonomic symptoms and restlessness. To better understand the pathophysiology of cluster headache, we used RNA sequencing to identify differentially expressed genes and pathways in whole blood of patients with episodic (n = 19) or chronic (n = 20) cluster headache in comparison with headache-free controls (n = 20). RNA was subjected to globin reduction before sequencing","abstract":"Cluster headache is a relatively rare headache disorder, typically characterized by multiple daily, short-lasting attacks of excruciating, unilateral (peri-)orbital or temporal pain associated with autonomic symptoms and restlessness. To better understand the pathophysiology of cluster headache, we used RNA sequencing to identify differentially expressed genes and pathways in whole blood of patients with episodic (n = 19) or chronic (n = 20) cluster headache in comparison with headache-free controls (n = 20). RNA was subjected to globin reduction before sequencing","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001920","title":"Array-based mRNA expression profiling of human hair follicle samples","description":"The dataset contains array-based genome-wide expression data for 120 human hair follicle samples from the occipital scalp area of healthy male donors","abstract":"The dataset contains array-based genome-wide expression data for 120 human hair follicle samples from the occipital scalp area of healthy male donors","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001921","title":"Array-based miRNA expression profiling of human hair follicle samples","description":"The dataset contains array-based genome-wide miRNA expression data for 25 human hair follicle samples from the frontal and occipital scalp area of healthy male donors","abstract":"The dataset contains array-based genome-wide miRNA expression data for 25 human hair follicle samples from the frontal and occipital scalp area of healthy male donors","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001922","title":"DNA methylation and the adverse metabolic outcomes of adiposity","description":"Overweight and obesity affect ~1.5 billion people worldwide, and are major risk factors for type-2 diabetes (T2D), cardiovascular disease and related metabolic and inflammatory disturbances.1,2 Although the mechanisms linking adiposity to its clinical sequelae are poorly understood, recent studies suggest that adiposity may influence DNA methylation,3-6 a key regulator of gene expression and molecular phenotype.7 Here we use epigenome-wide association to show that body mass index (BMI, a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci at P&lt;1x10-7, range P=9.2x10-8 to 6.0x10-46; N=10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find the methylation loci are enriched for functional genomic features in multiple tissues (P&lt;0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P&lt;9.0x10-6, range P=5.5x10-6 to 6.1x10-35, N=1,785 samples). The methylation loci identified highlight genes involved in lipid and lipoprotein metabolism, substrate transport, and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future type-2 diabetes (relative risk per 1SD increase in Methylation Risk Score: 2.3 [2.07-2.56]; P=1.1x10-54). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type-2 diabetes and other adverse clinical consequences of obesity.","abstract":"Overweight and obesity affect ~1.5 billion people worldwide, and are major risk factors for type-2 diabetes (T2D), cardiovascular disease and related metabolic and inflammatory disturbances.1,2 Although the mechanisms linking adiposity to its clinical sequelae are poorly understood, recent studies suggest that adiposity may influence DNA methylation,3-6 a key regulator of gene expression and molecular phenotype.7 Here we use epigenome-wide association to show that body mass index (BMI, a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci at P&lt;1x10-7, range P=9.2x10-8 to 6.0x10-46; N=10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find the methylation loci are enriched for functional genomic features in multiple tissues (P&lt;0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P&lt;9.0x10-6, range P=5.5x10-6 to 6.1x10-35, N=1,785 samples). The methylation loci identified highlight genes involved in lipid and lipoprotein metabolism, substrate transport, and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future type-2 diabetes (relative risk per 1SD increase in Methylation Risk Score: 2.3 [2.07-2.56]; P=1.1x10-54). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type-2 diabetes and other adverse clinical consequences of obesity.","study_type":"Other","pubmed_ids":[28002404],"external_links":null,"is_released":true,"released_date":"2016-08-02T15:46:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001923","title":"Deregulation of DUX4 and ERG in acute lymphoblastic leukemia","description":"Chromosomal rearrangements deregulating hematopoietic transcription factors are common leukemia-initiating lesions in acute lymphoblastic leukemia (ALL). Here, we show that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG are hallmarks of a subtype of B-progenitor ALL with a distinct gene expression profile that comprises up to 7% of B-ALL. DUX4 rearrangement and overexpression is present in all cases, and is accompanied by profound transcriptional deregulation of ERG, frequent ERG deletion and expression of a truncated ERG isoform, ERGalt. ERGalt utilizes a non-canonical first exon that is bound by DUX4 and induces its expression....","abstract":"Chromosomal rearrangements deregulating hematopoietic transcription factors are common leukemia-initiating lesions in acute lymphoblastic leukemia (ALL). Here, we show that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG are hallmarks of a subtype of B-progenitor ALL with a distinct gene expression profile that comprises up to 7% of B-ALL. DUX4 rearrangement and overexpression is present in all cases, and is accompanied by profound transcriptional deregulation of ERG, frequent ERG deletion and expression of a truncated ERG isoform, ERGalt. ERGalt utilizes a non-canonical first exon that is bound by DUX4 and induces its expression....","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-08-02T22:21:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001924","title":"MIBS MGS","description":"Metagenomic sequencing of the human gut in Maastricht IBS studies, cases and controls.","abstract":"Metagenomic sequencing of the human gut in Maastricht IBS studies, cases and controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-08-04T19:28:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001925","title":"BCR_MV_PBMCs","description":"A cohort of children in the Netherlands was recently infected by measles virus, due to lack of vaccination and in this instance pre and post measles infection peripheral blood samples were obtained. In collaboration with Dr Rik de Swart we will explore the impact of measles infection on B cell immune repertoires.  We will use methods for antigen-specific sorting of B cell populations already established for human and macaque B cell based on the B cell subset markers after exposure to measles virus and characterise antigen-specific and total B cells populations using methods for high-throughput sequencing of B-cell receptors already established in our group.","abstract":"A cohort of children in the Netherlands was recently infected by measles virus, due to lack of vaccination and in this instance pre and post measles infection peripheral blood samples were obtained. In collaboration with Dr Rik de Swart we will explore the impact of measles infection on B cell immune repertoires.  We will use methods for antigen-specific sorting of B cell populations already established for human and macaque B cell based on the B cell subset markers after exposure to measles virus and characterise antigen-specific and total B cells populations using methods for high-throughput sequencing of B-cell receptors already established in our group.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001926","title":"Mesenchymal inflammation drives genotoxic stress in hematopoietic stem cells and predicts disease evolution in human pre-leukemia","description":"Mesenchymal niche cells may drive tissue failure and malignant transformation in the hematopoietic system but the molecular mechanisms and their relevance to human disease remain poorly defined. We demonstrated that perturbation of mesenchymal cells in a mouse model of the preleukemic disorder Shwachman-Diamond syndrome induces mitochondrial dysfunction, oxidative stress and activation of DNA damage responses in hematopoietic stem and progenitor cells. In this study we demonstrate, through massive parallel RNA sequencing of highly purified mesenchymal cells in a range of human preleukemic syndromes, TP53-S100A8/9-TLR4 inflammatory signaling as a common driving mechanism of genotoxic stress, which could be attenuated by TLR4 blockade. S100A8/9 expression in mesenchymal cells predicted outcome in myelodysplastic syndromes, the principal human preleukemic condition, independent of known prognostic variables. Collectively, findings reveal a concept of mesenchymal niche-induced genotoxic stress in heterotypic stem and progenitor cells through inflammatory signaling as an actionable determinant of disease outcome in human preleukemia. The data further provide novel conceptual and mechanistic insights into the intimate link between inflammation and cancer.","abstract":"Mesenchymal niche cells may drive tissue failure and malignant transformation in the hematopoietic system but the molecular mechanisms and their relevance to human disease remain poorly defined. We demonstrated that perturbation of mesenchymal cells in a mouse model of the preleukemic disorder Shwachman-Diamond syndrome induces mitochondrial dysfunction, oxidative stress and activation of DNA damage responses in hematopoietic stem and progenitor cells. In this study we demonstrate, through massive parallel RNA sequencing of highly purified mesenchymal cells in a range of human preleukemic syndromes, TP53-S100A8/9-TLR4 inflammatory signaling as a common driving mechanism of genotoxic stress, which could be attenuated by TLR4 blockade. S100A8/9 expression in mesenchymal cells predicted outcome in myelodysplastic syndromes, the principal human preleukemic condition, independent of known prognostic variables. Collectively, findings reveal a concept of mesenchymal niche-induced genotoxic stress in heterotypic stem and progenitor cells through inflammatory signaling as an actionable determinant of disease outcome in human preleukemia. The data further provide novel conceptual and mechanistic insights into the intimate link between inflammation and cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-08-05T15:41:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001927","title":"Targeted sequencing for Korean Diffuse Gastric Cancer","description":"Gastric cancers in young patients are aggressive and predominantly of diffuse histology. Also, they are more frequent in female. Targeted sequencing was performed in the Early and Late onset diffuse gastric cancer cohorts for 10 significantly recurrent mutations that were identified in the Early onset diffuse gastric cancer WES cohort","abstract":"Gastric cancers in young patients are aggressive and predominantly of diffuse histology. Also, they are more frequent in female. Targeted sequencing was performed in the Early and Late onset diffuse gastric cancer cohorts for 10 significantly recurrent mutations that were identified in the Early onset diffuse gastric cancer WES cohort","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001928","title":"An integrative analysis of Pancreatic adenocarcinoma (PDAC)","description":"Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies and a major health problem. Patient-derived xenografts (PDX) are appearing as a prime approach for preclinical studies despite being insufficiently characterized as a model of the human disease and its diversity. We generated subcutaneous PDX from PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). The extensive multiomics characterization of the xenografts demonstrated that PDX is a suitable model for preclinical studies, representing the diversity of the primary cancers.","abstract":"Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies and a major health problem. Patient-derived xenografts (PDX) are appearing as a prime approach for preclinical studies despite being insufficiently characterized as a model of the human disease and its diversity. We generated subcutaneous PDX from PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). The extensive multiomics characterization of the xenografts demonstrated that PDX is a suitable model for preclinical studies, representing the diversity of the primary cancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001929","title":"Exome sequencing of 96 French-Canadians","description":"Exome sequencing was performed to validate the VCF and population frequencies inferred from RNA-seq data. Whole-exome sequencing was performed for 96 French-Canadian individuals from Montreal, Québec City and Saguenay. Exome paired-end library construction was performed using the TruSeq Exome Enrichment and TruSeq DNA LT Sample Prep v2 kits (Illumina) prior to 100-bp paired-end sequencing on the HiSeq 2000 platform using six samples per sequencing lane. On average, we achieved a coverage of ~40X across the nuclear exome.","abstract":"Exome sequencing was performed to validate the VCF and population frequencies inferred from RNA-seq data. Whole-exome sequencing was performed for 96 French-Canadian individuals from Montreal, Québec City and Saguenay. Exome paired-end library construction was performed using the TruSeq Exome Enrichment and TruSeq DNA LT Sample Prep v2 kits (Illumina) prior to 100-bp paired-end sequencing on the HiSeq 2000 platform using six samples per sequencing lane. On average, we achieved a coverage of ~40X across the nuclear exome.","study_type":"Other","pubmed_ids":[24763589],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001930","title":"Hi-C dataset for testicular germ cell tumour GWAS risk loci, as described in the Oncoarray Litchfield et al. 2016 paper.","description":"Genome-wide association studies (GWAS) have transformed our understanding of testicular germ cell tumour (TGCT) susceptibility but much of the heritability remains unexplained. Here we report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 7,319 TGCT cases and 23,082 controls. We identify 19 new TGCT risk loci, approximately doubling the number of known TGCT risk loci to 44. By performing in-situ Hi-C in TGCT cells, we establish a network of physical interactions between all 44 TGCT risk SNPs and candidate causal genes. Our findings reveal widespread disruption of developmental transcriptional regulators as a basis of disease susceptibility, consistent with failed primordial germ cell differentiation as an initiating step in TGCT oncogenesis1. Defective microtubule assembly and dysregulation of KIT-MAPK signalling also feature as recurrently disrupted pathways. Our findings support a polygenic model of disease risk and provide insight into the biological basis of TGCT.","abstract":"Genome-wide association studies (GWAS) have transformed our understanding of testicular germ cell tumour (TGCT) susceptibility but much of the heritability remains unexplained. Here we report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 7,319 TGCT cases and 23,082 controls. We identify 19 new TGCT risk loci, approximately doubling the number of known TGCT risk loci to 44. By performing in-situ Hi-C in TGCT cells, we establish a network of physical interactions between all 44 TGCT risk SNPs and candidate causal genes. Our findings reveal widespread disruption of developmental transcriptional regulators as a basis of disease susceptibility, consistent with failed primordial germ cell differentiation as an initiating step in TGCT oncogenesis1. Defective microtubule assembly and dysregulation of KIT-MAPK signalling also feature as recurrently disrupted pathways. Our findings support a polygenic model of disease risk and provide insight into the biological basis of TGCT.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-08-09T11:23:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001931","title":"Methods for systematic next generation oncology biomarker development","description":"OncoTrack, “Methods for systematic next generation oncology biomarker development”, is an international consortium of over 80 scientists, that has launched one of Europe’s largest collaborative academic-industry research projects to develop and assess novel approaches for identification of new markers for colon cancer. This unique five year project brings together top scientists from European academic institutions offering a wide range of expertise, and partners them with pharmaceutical companies.","abstract":"OncoTrack, “Methods for systematic next generation oncology biomarker development”, is an international consortium of over 80 scientists, that has launched one of Europe’s largest collaborative academic-industry research projects to develop and assess novel approaches for identification of new markers for colon cancer. This unique five year project brings together top scientists from European academic institutions offering a wide range of expertise, and partners them with pharmaceutical companies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001932","title":"Genome_wide_CRISPR_Cas9_screening_of_Human_Organoids","description":"In this study we will exploit the bacterial clustered regularly interspaced short palindromic repeats (CRISPR) system to perform a genome-wide single-guide RNA (sgRNA) library to screen for genes required for proliferation and survival in human organoids. ","abstract":"We will use  large-scale drug and CRISPR screens to systematically identify vulnerabilities in organoids revealing the set of genes essential for the growth of  patient-derived normal and cancer organoids.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-08-09T17:08:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001933","title":"Mutant_clone_mapping_in_normal_oesohagus_and_skin","description":"We will use targeted exome sequencing to examine normal appearing oesophageal epithelium and skin to determine the mutational burden.  DNA will be extracted from epithelia of a defined size and we will overlay positional information from the epithelial pieces to give clone maps over a wide area.  This will be done in both oesophageal epithelium and skin","abstract":"We will use targeted exome sequencing to examine normal appearing oesophageal epithelium and skin to determine the mutational burden.  DNA will be extracted from epithelia of a defined size and we will overlay positional information from the epithelial pieces to give clone maps over a wide area.  This will be done in both oesophageal epithelium and skin","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-08-09T13:57:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001934","title":"Genomic characterization of NUT midline carcinoma","description":"In this study, we sequenced two NUT midline carcinoma genomes. Analysis of rearrangement breakpoint provided information on the generating event of BRD-NUT rearrangements. Mutational signature analysis also revealed biological process during tumorigenesis of NUT midline carcinomas.","abstract":"In this study, we sequenced two NUT midline carcinoma genomes. Analysis of rearrangement breakpoint provided information on the generating event of BRD-NUT rearrangements. Mutational signature analysis also revealed biological process during tumorigenesis of NUT midline carcinomas.","study_type":"Other","pubmed_ids":[28203693],"external_links":null,"is_released":true,"released_date":"2016-08-09T14:40:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001935","title":"Ethiopian_Genome_Project_Genotyping","description":"The Ethiopian area stands among the most ancient ones ever occupied by human populations and their ancestors. It is the location of the earliest known fossils of anatomically modern humans and the most likely source of the populations that migrated out of Africa to populate the rest of the world. Furthermore, the present populations show great cultural, linguistic and historic diversity which makes them important for understanding African genetic variation. Following the typing of 300 diverse Ethiopian samples on the Illumina Omni 1M (see Human Variability in Ethiopia project, previously approved by the Genotyping Committee) we have chosen six populations that represent Ethiopian genetic diversity for\nfurther\ngenotyping\nand\nsequencing,\nand\nobtained\nfresh\nsamples.\nThis\napplication\ncovers\ngenotyping;\nsequencing\nwill\nbe\nthe\nsubject\nof\nseparate\napplications.\nHere,\nwe\npropose\nto\ngenotype\nthe\n300\nsamples\nusing\nthe\nIllumina\nOmni\n2.5M\nchip.\nGenotyping\nis\nnecessary\nto\ninterpret\nthe\nlow-­‐coverage\nsequence\ndata\nthat\nwill\nbe\ngenerated\nas\npart\nof\nHuman\nvariation\nAims\n1\nand\n2.\nWe\nhave\nchosen\nthe\nOmni\n2.5M\nafter\ndiscussions\nwith\nManj\nso\nthat\nthe\nEthiopian\nsamples\ncan\nin\naddition\nbe\nintegrated\ninto\nthe\nAfrican\nGenome\nVariation\nproject,\nwhich\nis\nbased\non\nthis\nchip\nbut\nlacks\nsamples\nfrom\nEthiopia\nor\nnearby.","abstract":"The\nEthiopian\narea\nstands\namong\nthe\nmost\nancient\nones\never\noccupied\nby\nhuman\npopulations\nand\ntheir\nancestors.\nIt\nis\nthe\nlocation\nof\nthe\nearliest\nknown\nfossils\nof\nanatomically\nmodern\nhumans\nand\nthe\nmost\nlikely\nsource\nof\nthe\npopulations\nthat\nmigrated\nout\nof\nAfrica\nto\npopulate\nthe\nrest\nof\nthe\nworld.\nFurthermore,\nthe\npresent\npopulations\nshow\ngreat\ncultural,\nlinguistic\nand\nhistoric\ndiversity\nwhich\nmakes\nthem\nimportant\nfor\nunderstanding\nAfrican\ngenetic\nvariation.\nFollowing\nthe\ntyping\nof\n300\ndiverse\nEthiopian\nsamples\non\nthe\nIllumina\nOmni\n1M\n(see\nHuman\nVariability\nin\nEthiopia\nproject,\npreviously\napproved\nby\nthe\nGenotyping\nCommittee)\nwe\nhave\nchosen\nsix\npopulations\nthat\nrepresent\nEthiopian\ngenetic\ndiversity\nfor\nfurther\ngenotyping\nand\nsequencing,\nand\nobtained\nfresh\nsamples.\nThis\napplication\ncovers\ngenotyping;\nsequencing\nwill\nbe\nthe\nsubject\nof\nseparate\napplications.\nHere,\nwe\npropose\nto\ngenotype\nthe\n300\nsamples\nusing\nthe\nIllumina\nOmni\n2.5M\nchip.\nGenotyping\nis\nnecessary\nto\ninterpret\nthe\nlow-­‐coverage\nsequence\ndata\nthat\nwill\nbe\ngenerated\nas\npart\nof\nHuman\nvariation\nAims\n1\nand\n2.\nWe\nhave\nchosen\nthe\nOmni\n2.5M\nafter\ndiscussions\nwith\nManj\nso\nthat\nthe\nEthiopian\nsamples\ncan\nin\naddition\nbe\nintegrated\ninto\nthe\nAfrican\nGenome\nVariation\nproject,\nwhich\nis\nbased\non\nthis\nchip\nbut\nlacks\nsamples\nfrom\nEthiopia\nor\nnearby.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001936","title":"Transcriptional_analysis_of_single_cell_neonatal_foreskin_keratinocytes","description":"Neonatal foreskin keratinocytes are cultured and then collected without trypsinisation using scraping and separated into single cell suspension using the gentlemacs and ice cold PBS.  Cells are flow sorted straight into lysis buffer provided by the single cell facility.","abstract":"Earlier work has shown that there are two types of colonies in an NFSK culture; balanced and expanding.  Balanced colonies have equal proportions of proliferative and differentiating cells.  Expanding colonies have a high number of proliferative cells.  We aim to identify single cell transcriptional differences between cells from these two types of colonies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001937","title":"IHEC DEEP Release August 2016","description":"Additional sequencing data for the German IHEC contribution (DEEP, http://deep.dkfz.de/, http://www.deutsches-epigenom-programm.de/).\nThis is the additional data released in August 2016.\n\nContains datatypes:\n- Whole Genome Bisulfite sequencing\n- ChipSeq (H3K27ac, H3K27me3, H3K36me3, H3K4me1, H3K4me3, H3K9me3, Input)\n- tRNA – not unmapped\n- mRNA\n- snRNA\n- Dnase Hypersensitive sites\n- RRBS\n- NOMe","abstract":"Additional sequencing data for the German IHEC contribution (DEEP, http://deep.dkfz.de/, http://www.deutsches-epigenom-programm.de/).\nThis is the additional data released in August 2016.\n\nContains datatypes:\n- Whole Genome Bisulfite sequencing\n- ChipSeq (H3K27ac, H3K27me3, H3K36me3, H3K4me1, H3K4me3, H3K9me3, Input)\n- tRNA – not unmapped\n- mRNA\n- snRNA\n- Dnase Hypersensitive sites\n- RRBS\n- NOMe","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-08-12T11:54:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001938","title":"There are 5-pairs WGS and 15-pairs WXS of LICA-CN project data to analysis the liver cancer.","description":"There are 5-pairs WGS and 15-pairs WXS of LICA-CN project data which from the the fourth military medical university to analysis the liver cancer","abstract":"There are 5-pairs WGS and 15-pairs WXS of LICA-CN project data which from the the fourth military medical university to analysis the liver cancer","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001939","title":"There are 97 pairs WES+ 7 normal WES of LAML-CN project to anylysis leukemia.","description":"There are 97 pairs WES+ 7 normal WES of LAML-CN project data from Chinese Academy of Sciences to anylysis leukemia.","abstract":"There are 97 pairs WES+ 7 normal WES of LAML-CN project data from Chinese Academy of Sciences to anylysis leukemia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001940","title":"Impact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation","description":"Presurgical studies allow study of the relationship between mutations and response of estrogen receptor positive (ER+) breast cancer to aromatase inhibitors (AIs) but have been limited to small biopsies. Here in Phase I of this study, we perform exome sequencing on baseline, surgical core-cuts and blood from 60 patients (40 AI treated, 20 Controls). In poor responders (based on Ki67 change) we find significantly more somatic mutations than good responders. Subclones exclusive to baseline or surgical cores   occur in approximately 30% of tumours. In Phase II we combine targeted sequencing on another 28 treated patients with Phase I. We find six genes frequently mutated: PIK3CA, TP53, CDH1, MLL3, ABCA13 and FLG with 71% concordance between paired cores. TP53 mutations are associated with poor response. We conclude that multiple biopsies are essential for confident mutational profiling of ER+ breast cancer and TP53 mutations are associated with resistance to oestrogen deprivation therapy.","abstract":"Presurgical studies allow study of the relationship between mutations and response of estrogen receptor positive (ER+) breast cancer to aromatase inhibitors (AIs) but have been limited to small biopsies. Here in Phase I of this study, we perform exome sequencing on baseline, surgical core-cuts and blood from 60 patients (40 AI treated, 20 Controls). In poor responders (based on Ki67 change) we find significantly more somatic mutations than good responders. Subclones exclusive to baseline or surgical cores   occur in approximately 30% of tumours. In Phase II we combine targeted sequencing on another 28 treated patients with Phase I. We find six genes frequently mutated: PIK3CA, TP53, CDH1, MLL3, ABCA13 and FLG with 71% concordance between paired cores. TP53 mutations are associated with poor response. We conclude that multiple biopsies are essential for confident mutational profiling of ER+ breast cancer and TP53 mutations are associated with resistance to oestrogen deprivation therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-08-15T12:43:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001941","title":"Evolution_of_the_cancer_epigenome_in_myeloproliferative_neoplasms_","description":"Evolution of the cancer epigenome in myeloproliferative neoplasms.","abstract":"Cancer clones emerge and evolve through somatic mutation acquisition and Darwinian selection, but the dynamics of clonal evolution remain poorly understood and predicting disease progression remains a real challenge. Genes that regulate the epigenome are clearly important targets of mutations in cancer, but the mechanisms by which they drive tumour evolution remain unknown.\nThe myeloproliferative neoplasms (MPN) are haematopoietic disorders that represent an excellent model to study genomic and epigenomic evolution in human cancers: (i) They are genetically well-defined with disease driving mutations in JAK2, CALR (which I described in 2013) or MPL, present alongside mutations in epigenetic regulators, such as, DNMT3A. (ii) Disease can be either stable, or progress to leukaemia or myelofibrosis, providing the opportunity to study the basis for these evolutionary differences, and (iii) Primary cells can be serially sampled at the clonal level enabling inter- and intra-clonal studies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-08-18T11:38:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001942","title":"Epigenomic and Genomic Correlates of Aggression in Curable Prostate Cancer, Extended","description":"TBD","abstract":"TBD","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001943","title":"Histone Acetylome-wide Association Study of Autism Spectrum Disorder","description":"H3K27ac ChIP-seq were performed on postmortem samples from autism spectrum disorder and matched control brains. Tissues were chosen from three brain regions: prefrontal cortex, temporal cortex and cerebellum.","abstract":"H3K27ac ChIP-seq were performed on postmortem samples from autism spectrum disorder and matched control brains. Tissues were chosen from three brain regions: prefrontal cortex, temporal cortex and cerebellum.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-08-24T10:09:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001944","title":"Vasculogenic Mimicry in Small Cell Lung Cancer","description":"Small Cell Lung Cancer (SCLC) is characterised by prevalent circulating tumour cells (CTCs), early metastasis and poor prognosis. We show that SCLC patients (37/38) have rare CTC subpopulations co-expressing Vascular Endothelial-Cadherin (VE-Cadherin) and cytokeratins consistent with vasculogenic mimicry (VM), a process whereby tumour cells form ‘endothelial like’ vessels. Single cell genomic analysis reveals characteristic SCLC genomic changes in both VE-Cadherin positive and negative CTCs. Higher levels of VM are associated with worse overall survival in 41 limited stage patients’ biopsies (p&lt;0.025). VM vessels are also observed in 9/10 CTC patient-derived explants (CDX), where molecular analysis of fractionated VE-Cadherin positive cells uncovered copy number alterations and mutated TP53, confirming human tumour origin. VE-Cadherin is required for VM in NCI-H446 SCLC xenografts, where VM decreases tumour latency and, despite increased cisplatin intra-tumour delivery, decreases cisplatin efficacy. The functional significance of VM in SCLC suggests VM regulation may provide new targets for therapeutic intervention.","abstract":"Small Cell Lung Cancer (SCLC) is characterised by prevalent circulating tumour cells (CTCs), early metastasis and poor prognosis. We show that SCLC patients (37/38) have rare CTC subpopulations co-expressing Vascular Endothelial-Cadherin (VE-Cadherin) and cytokeratins consistent with vasculogenic mimicry (VM), a process whereby tumour cells form ‘endothelial like’ vessels. Single cell genomic analysis reveals characteristic SCLC genomic changes in both VE-Cadherin positive and negative CTCs. Higher levels of VM are associated with worse overall survival in 41 limited stage patients’ biopsies (p&lt;0.025). VM vessels are also observed in 9/10 CTC patient-derived explants (CDX), where molecular analysis of fractionated VE-Cadherin positive cells uncovered copy number alterations and mutated TP53, confirming human tumour origin. VE-Cadherin is required for VM in NCI-H446 SCLC xenografts, where VM decreases tumour latency and, despite increased cisplatin intra-tumour delivery, decreases cisplatin efficacy. The functional significance of VM in SCLC suggests VM regulation may provide new targets for therapeutic intervention.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001945","title":"Single cell Transcriptomic Analysis of Cellular Heterogeneity in Human Colorectal Tumors","description":"1,591 single cells from 11 colorectal cancer patients were profiled using Fluidigm based single cell RNA-seq protocol to characterized cellular heterogeneity of colorectal cancer. 630 single cells from 7 cell lines were profiled similarly to benchmark de novo cell type identification algorithms.","abstract":"1,591 single cells from 11 colorectal cancer patients were profiled using Fluidigm based single cell RNA-seq protocol to characterized cellular heterogeneity of colorectal cancer. 630 single cells from 7 cell lines were profiled similarly to benchmark de novo cell type identification algorithms.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-08-25T07:27:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001946","title":"CRC Promoter capture Hi-C","description":"Genome organisation determines chromosome interactions between regulatory elements, such as promoters and enhancers, influencing gene expression. Despite the fact that it is possible to assess whether a gene is actively transcribed, it has been challenging to point out the genomic regions that are involved in the regulation of a particular gene. We are interested in better understanding the interactions between promoters and their regulatory elements in colorectal cancer in order to unveil novel non-coding regions which might have a role in tumour development. To do so, we utilise the HiC method complemented with promoter capture in combination with NGS to map promoter interactions in two CRC cell lines, representing two distinct CRC subtypes.","abstract":"Genome organisation determines chromosome interactions between regulatory elements, such as promoters and enhancers, influencing gene expression. Despite the fact that it is possible to assess whether a gene is actively transcribed, it has been challenging to point out the genomic regions that are involved in the regulation of a particular gene. We are interested in better understanding the interactions between promoters and their regulatory elements in colorectal cancer in order to unveil novel non-coding regions which might have a role in tumour development. To do so, we utilise the HiC method complemented with promoter capture in combination with NGS to map promoter interactions in two CRC cell lines, representing two distinct CRC subtypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-08-26T10:48:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001947","title":"Distinguishing_indolent_from_aggressive_ductal_carcinoma_in_situ__DCIS___Pilot","description":"With the widespread adoption of breast screening, ductal carcinoma in situ (DCIS) has come to represent 20-25% of breast neoplasia diagnosed through screening, some 8,000 women annually in the UK, 2,400 in the Netherlands, and over 60,000 women per year in the US. Conventional management  includes surgery, supplemented by radiotherapy and/or endocrine therapy, but over-treats the majority of DCIS as ~1% recur annually and breast cancer mortality is ~3% at 20 years. Uncertainty as to which DCIS lesions will progress to invasive cancer or, after excision, which will return with recurrent DCIS or invasive breast cancer drives this overtreatment. Characterisation of the DCIS with lethal potential from the majority of non-lethal DCIS would impact on a significant proportion of the tens of thousands of women in the UK and globally who currently undergo radical treatment (surgery, radiotherapy, endocrine therapy), without a survival benefit, but bear the lifelong consequences of therapy.\n\nThe pressing need is therefore to distinguish the relatively small proportion of women with DCIS who will\nsubsequently die of (invasive) breast cancer from the majority with DCIS who are currently overtreated. Thus, to distinguish aggressive from indolent DCIS we will develop, cross-validate, and prospectively test molecular markers utilising clinical material available from retrospective and prospective clinical studies in the UK, Europe and US.","abstract":"With the widespread adoption of breast screening, ductal carcinoma in situ (DCIS) has come to represent 20-25% of breast neoplasia diagnosed through screening, some 8,000 women annually in the UK, 2,400 in the Netherlands, and over 60,000 women per year in the US. Conventional management  includes surgery, supplemented by radiotherapy and/or endocrine therapy, but over-treats the majority of DCIS as ~1% recur annually and breast cancer mortality is ~3% at 20 years. Uncertainty as to which DCIS lesions will progress to invasive cancer or, after excision, which will return with recurrent DCIS or invasive breast cancer drives this overtreatment. Characterisation of the DCIS with lethal potential from the majority of non-lethal DCIS would impact on a significant proportion of the tens of thousands of women in the UK and globally who currently undergo radical treatment (surgery, radiotherapy, endocrine therapy), without a survival benefit, but bear the lifelong consequences of therapy.\n\nThe pressing need is therefore to distinguish the relatively small proportion of women with DCIS who will\nsubsequently die of (invasive) breast cancer from the majority with DCIS who are currently overtreated. Thus, to distinguish aggressive from indolent DCIS we will develop, cross-validate, and prospectively test molecular markers utilising clinical material available from retrospective and prospective clinical studies in the UK, Europe and US.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001948","title":"Exome sequencing of samples taken at multipl time points to monitor therapy response in AML","description":"As part of our individualized systems medicine program, personalized treatment options are identified and administered to chemorefractory AML patients based on exome sequencing and ex-vivo drug sensitivity and resistance testing data. In this study, we developed this approach further to take into account clonal heterogeneity and analyzed responses of 13 AML patients to chemotherapy and six patients to targeted treatments by using exome and ultra-deep amplicon resequencing. The data submitted includes fastq files from exome sequencing of multiple time-point samples collected from the 13 patients. In this study we identified rare subclonal variants present at diagnosis or later relapse samples and developed a correlation-based method to compare subclonal responses in serial samples across multiple time-points. Significant subclone-specific responses were observed subsequent to chemotherapy and specifically to targeted therapy in five patients.","abstract":"As part of our individualized systems medicine program, personalized treatment options are identified and administered to chemorefractory AML patients based on exome sequencing and ex-vivo drug sensitivity and resistance testing data. In this study, we developed this approach further to take into account clonal heterogeneity and analyzed responses of 13 AML patients to chemotherapy and six patients to targeted treatments by using exome and ultra-deep amplicon resequencing. The data submitted includes fastq files from exome sequencing of multiple time-point samples collected from the 13 patients. In this study we identified rare subclonal variants present at diagnosis or later relapse samples and developed a correlation-based method to compare subclonal responses in serial samples across multiple time-points. Significant subclone-specific responses were observed subsequent to chemotherapy and specifically to targeted therapy in five patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-01T12:37:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001949","title":"Targeted sequencing analysis for MDS with HSCT","description":"Targeted capture sequencing for cases with MDS who were subjected to unrelated bone marrow transplantation via Japan marrow donor program","abstract":"Targeted capture sequencing for cases with MDS who were subjected to unrelated bone marrow transplantation via Japan marrow donor program","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-01T14:36:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001950","title":"Mutational landscape of renal cell carcinoma with venous tumor thrombus","description":"Renal cell carcinoma with venous tumor thrombus opens the unique opportunity to investigate the clonal evolution of a tumor in two fundamentally different compartments i.e., within the confinement of an organ and inside a large blood vessel. We performed multiregion whole exome sequencing of a total of 37 samples from five consecutive patients (normal tissue, n=5; primary tumors, n=16; tumor thrombi, n=16) to &gt;35-fold target coverage. Four patients had a clear cell RCC, one patient had a poorly differentiated type II papillary RCC (RCC-VTT-04). The latter patient had a friable thrombus, the others were of solid consistency.","abstract":"Renal cell carcinoma with venous tumor thrombus opens the unique opportunity to investigate the clonal evolution of a tumor in two fundamentally different compartments i.e., within the confinement of an organ and inside a large blood vessel. We performed multiregion whole exome sequencing of a total of 37 samples from five consecutive patients (normal tissue, n=5; primary tumors, n=16; tumor thrombi, n=16) to &gt;35-fold target coverage. Four patients had a clear cell RCC, one patient had a poorly differentiated type II papillary RCC (RCC-VTT-04). The latter patient had a friable thrombus, the others were of solid consistency.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-01T16:00:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001951","title":"Molecular analysis of circulating tumour cells identifies distinct profiles in chemosensitive and chemorefractory patients with small cell lung cancer","description":"In a search for profiles that distinguish chemosensitive versus chemorefractory SCLC disease, we examined copy number aberrations (CNA) in circulating tumour cells (CTCs) from pre-treatment SCLC blood samples. A CNA classifier was generated from 88 CTCs isolated from 13 patients (training set) then verified in 18 additional patients (112 CTC samples) (testing set) and in six SCLC patient-derived CTC explants explant tumours. These data highlight the potential utility of CTCs for molecular profiling and stratification of SCLC patients in future clinical trials.","abstract":"In a search for profiles that distinguish chemosensitive versus chemorefractory SCLC disease, we examined copy number aberrations (CNA) in circulating tumour cells (CTCs) from pre-treatment SCLC blood samples. A CNA classifier was generated from 88 CTCs isolated from 13 patients (training set) then verified in 18 additional patients (112 CTC samples) (testing set) and in six SCLC patient-derived CTC explants explant tumours. These data highlight the potential utility of CTCs for molecular profiling and stratification of SCLC patients in future clinical trials.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-05T14:47:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001952","title":"Genomic Analyses Identify Recurrent MEF2D Fusions in Acute Lymphoblastic Leukemia","description":"Chromosomal rearrangements are initiating events in acute lymphoblastic leukemia (ALL). Here, using RNA-sequencing (RNAseq) of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1164 B-ALL cases identified 30 cases with MEF2D rearrangements which include an additional fusion partner, FOXJ2, thus MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age, and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitors treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukemia, for which new therapeutic approaches should be considered.","abstract":"Chromosomal rearrangements are initiating events in acute lymphoblastic leukemia (ALL). Here, using RNA-sequencing (RNAseq) of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1164 B-ALL cases identified 30 cases with MEF2D rearrangements which include an additional fusion partner, FOXJ2, thus MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age, and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitors treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukemia, for which new therapeutic approaches should be considered.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-06T02:10:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001953","title":"Comprehensive molecular profiling identifies novel genetic drivers and subtypes underlying medulloblastoma","description":"Current therapies for medulloblastoma (MB), a highly malignant childhood brain tumor, impose debilitating effects on the developing child, warranting the development of molecularly targeted treatments with reduced toxicities. Prior studies have failed to disclose the full spectrum of driver genes and molecular processes operative in MB or adequately explain heterogeneity among molecular subgroups. Herein, we detail the somatic landscape across 491 sequenced MBs and molecular heterogeneity amongst 1,256 epigenetically analyzed cases, identifying subgroup-specific mutational signatures, driver genes, and pathway alterations including previously unappreciated actionable therapeutic targets. Integrative approaches for assigning driver genes to subgroups explained &gt;65-70% of Group 3 and Group 4, doubling previous knowledge. Novel subtypes underlying Group 3 and Group 4 were differentially enriched for specific driver events, including hotspot in-frame indels targeting KBTBD4 and ‘enhancer hijacking’ driving activation of PRDM6. Thus, application of integrative genomics to an unprecedented cohort of clinical samples derived from a single childhood cancer entity has disclosed a series of new cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for treating MB.","abstract":"Current therapies for medulloblastoma (MB), a highly malignant childhood brain tumor, impose debilitating effects on the developing child, warranting the development of molecularly targeted treatments with reduced toxicities. Prior studies have failed to disclose the full spectrum of driver genes and molecular processes operative in MB or adequately explain heterogeneity among molecular subgroups. Herein, we detail the somatic landscape across 491 sequenced MBs and molecular heterogeneity amongst 1,256 epigenetically analyzed cases, identifying subgroup-specific mutational signatures, driver genes, and pathway alterations including previously unappreciated actionable therapeutic targets. Integrative approaches for assigning driver genes to subgroups explained &gt;65-70% of Group 3 and Group 4, doubling previous knowledge. Novel subtypes underlying Group 3 and Group 4 were differentially enriched for specific driver events, including hotspot in-frame indels targeting KBTBD4 and ‘enhancer hijacking’ driving activation of PRDM6. Thus, application of integrative genomics to an unprecedented cohort of clinical samples derived from a single childhood cancer entity has disclosed a series of new cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for treating MB.","study_type":"Other","pubmed_ids":[28726821],"external_links":null,"is_released":true,"released_date":"2016-09-06T11:53:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001954","title":"Genomics of enteropathy associated T cell lymphoma (EATL)","description":"Enteropathy-associated T cell lymphoma (EATL) is a lethal and the most common neoplastic complication of celiac disease. In this study, we applied whole exome sequencing in 69 EATL tumors to define the genetic landscape of EATLs. The most frequently mutated gene in EATL was SETD2 (32% of cases), with loss of function mutations comprising a large proportion (41%) of those mutations. The JAK-STAT pathway was the most frequently mutated signaling pathway, with mutations in STAT5B being the most common, followed by JAK1, JAK3, STAT3, and the negative regulator of the pathway, SOCS1. We also identified mutations in NRAS and KRAS, as well as TP53 and TERT. Interestingly, the two types of EATL had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. Gene expression analysis of the two types of EATL identify robust differences in transcriptional profiles. We further modeled the effects of SETD2 loss in vivo by developing a T cell specific knockout mouse model. These mice manifested an expansion of γδ T cells that identify novel roles for SETD2 in T cell development and lymphomagenesis. Together, our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease, and may inform future classification schemes.","abstract":"Enteropathy-associated T cell lymphoma (EATL) is a lethal and the most common neoplastic complication of celiac disease. In this study, we applied whole exome sequencing in 69 EATL tumors to define the genetic landscape of EATLs. The most frequently mutated gene in EATL was SETD2 (32% of cases), with loss of function mutations comprising a large proportion (41%) of those mutations. The JAK-STAT pathway was the most frequently mutated signaling pathway, with mutations in STAT5B being the most common, followed by JAK1, JAK3, STAT3, and the negative regulator of the pathway, SOCS1. We also identified mutations in NRAS and KRAS, as well as TP53 and TERT. Interestingly, the two types of EATL had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. Gene expression analysis of the two types of EATL identify robust differences in transcriptional profiles. We further modeled the effects of SETD2 loss in vivo by developing a T cell specific knockout mouse model. These mice manifested an expansion of γδ T cells that identify novel roles for SETD2 in T cell development and lymphomagenesis. Together, our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease, and may inform future classification schemes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-06T21:39:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001955","title":"WES of non-HCC liver injury","description":"To understand the genomic landscape of pre-cancerous liver disease, we have generated whole exome sequencing dataset of liver tissue from patients without overt liver injury (12 samples) and cirrhotic patients without HCC (6 HCV-positive).","abstract":"To understand the genomic landscape of pre-cancerous liver disease, we have generated whole exome sequencing dataset of liver tissue from patients without overt liver injury (12 samples) and cirrhotic patients without HCC (6 HCV-positive).","study_type":"Other","pubmed_ids":[27631787],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001956","title":"Pacbio_GCT","description":"PacBio sequencing of giant cell tumour","abstract":"PacBio sequencing of giant cell tumour","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001957","title":"Relaxed selection during a recent human expansion","description":"To better understand and quantify the effect of a recent expansion process on the amount and  pattern of mutation load, we screened the ascending genealogies of 3916 individuals from the CARTaGENE cohort (Awadalla et al. 2013) that were linked to the BALSAC genealogical database (http://balsac.uqac.ca/). Using stringent criteria on the quality of genealogical information, we selected (front) individuals whose ancestors were as close as possible to the front of the colonization of Quebec, and (core) individuals whose ancestors were as far as possible from the front. We then sequenced these 102 individuals at very high coverage (mean 89.5X, range 67X-128X) for 106.5 Mb of exomic and UTR regions and contrasted their genomic diversity to detect if sites with various degrees of conservation and deleteriousness had been differentially impacted by selection.","abstract":"To better understand and quantify the effect of a recent expansion process on the amount and  pattern of mutation load, we screened the ascending genealogies of 3916 individuals from the CARTaGENE cohort (Awadalla et al. 2013) that were linked to the BALSAC genealogical database (http://balsac.uqac.ca/). Using stringent criteria on the quality of genealogical information, we selected (front) individuals whose ancestors were as close as possible to the front of the colonization of Quebec, and (core) individuals whose ancestors were as far as possible from the front. We then sequenced these 102 individuals at very high coverage (mean 89.5X, range 67X-128X) for 106.5 Mb of exomic and UTR regions and contrasted their genomic diversity to detect if sites with various degrees of conservation and deleteriousness had been differentially impacted by selection.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-09T16:09:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001958","title":"House_dust_mite","description":"Single cells from human blister were sorted and processed using smartseq2 protocol.","abstract":"This study aims to obtain a deeper understanding of the human skin response to allergens by characterizing the transcriptomic landscape of single cells","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001959","title":"The Simons Genome Diversity Project: 300 genomes from 142 diverse populations","description":"Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that in other non- Africans.","abstract":"Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that in other non- Africans.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-12T18:07:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001960","title":"Novel CNV contribution to schizophrenia from a genome wide study of 41,321 subjects","description":"Genomic copy number variants (CNVs) have been strongly implicated in the etiology schizophrenia (SCZ). However, apart from a small number of risk variants, elucidation of the CNV contribution to risk has been difficult due to the very low frequencies of risk alleles, all occurring in less than 1% of patients. We sought to address this obstacle through a collaborative effort unprecedented in psychiatry in which we applied a centralized analysis pipeline to a large SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden is observed in SCZ patients (OR=1.11, P=5.7e-15), and persists after excluding loci implicated in previous studies (OR=1.07, P=1.7e-6). CNV Burden is also enriched for genes associated with synaptic function (OR = 1.68, P = 2.8e-11) and neurobehavioral phenotypes in mouse (OR = 1.18, P= 7.3e-05). While only previously implicated loci surpass strict genome-wide testing correction, we identify “novel” CNVs (BH-FDR &lt; 0.05) that confer both protective and risk effects on SCZ and are predominantly mediated by non-allelic homologous recombination (NAHR). Our combined data find genome-wide significant support for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2.","abstract":"Genomic copy number variants (CNVs) have been strongly implicated in the etiology schizophrenia (SCZ). However, apart from a small number of risk variants, elucidation of the CNV contribution to risk has been difficult due to the very low frequencies of risk alleles, all occurring in less than 1% of patients. We sought to address this obstacle through a collaborative effort unprecedented in psychiatry in which we applied a centralized analysis pipeline to a large SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden is observed in SCZ patients (OR=1.11, P=5.7e-15), and persists after excluding loci implicated in previous studies (OR=1.07, P=1.7e-6). CNV Burden is also enriched for genes associated with synaptic function (OR = 1.68, P = 2.8e-11) and neurobehavioral phenotypes in mouse (OR = 1.18, P= 7.3e-05). While only previously implicated loci surpass strict genome-wide testing correction, we identify “novel” CNVs (BH-FDR &lt; 0.05) that confer both protective and risk effects on SCZ and are predominantly mediated by non-allelic homologous recombination (NAHR). Our combined data find genome-wide significant support for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2.","study_type":"Other","pubmed_ids":[9820031,15712379,17921354,18369103,18511947,18668038,18776909,18945720,19855392,20531469,20691406,20838587,21346763,21408211,21969575,21984752,22083728,22196331,22424231,22596160,22876571,23238724,24217254,25044748,25056061,25927380,26050040],"external_links":null,"is_released":true,"released_date":"2016-09-13T03:59:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001961","title":"Chromosome contacts in activated T cells identify autoimmune disease-candidate genes","description":"Autoimmune disease-associated DNA variants are preferentially found in regions with putative regulatory function in immune cells, particularly CD4+ T cells. Linking such regulatory elements to gene promoters in disease-relevant cells and contexts is essential to identify disease candidate genes. Here we show that the activation of CD4+ T cells invokes changes in the activity of regulatory elements and transcription of RNAs that correspond to changes in the expression of their interacting genes identified by promoter capture Hi-C (PCHi-C).","abstract":"Autoimmune disease-associated DNA variants are preferentially found in regions with putative regulatory function in immune cells, particularly CD4+ T cells. Linking such regulatory elements to gene promoters in disease-relevant cells and contexts is essential to identify disease candidate genes. Here we show that the activation of CD4+ T cells invokes changes in the activity of regulatory elements and transcription of RNAs that correspond to changes in the expression of their interacting genes identified by promoter capture Hi-C (PCHi-C).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-13T08:58:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001962","title":"-sc-1207, submitted by SC","description":"Automatically imported from SNP, please check &amp; update all information","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001963","title":"CLL_targeted_exome_sequencing","description":"Aim to characterise cancer gene landscape in CLL, particularly in cases with mutated POT1 gene. Treatment-naïve CLL cases will be interrogated by targeted exome sequencing using a cancer gene panel.","abstract":"Chronic lymphocyte leukaemia (CLL) is a  heterogeneous disease both genetically and clinically. Recently recurrent somatic mutations in the POT1 gene were identified in CLL and correlated with inferior prognosis. This study aims to evaluate the cancer gene landscape of POT1-mutated cases in order to identify collaborative genetic lesions  which may contribute to the poorer clinical outcome of POT1-mutated cases.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-13T11:54:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001964","title":"The_contribution_of_POT1_variants_to_sporadic_melanoma_development","description":"A case-control series of melanoma cases from Leeds, UK have been sequenced in the Fluidigm platform to identify genetic variants associated with sporadic melanoma development. Samples in which potentially contributing variants have been detected are being sequenced in an orthogonal platform for variant confirmation.","abstract":"A case-control series of melanoma cases from Leeds, UK have been sequenced in the Fluidigm platform to identify genetic variants associated with sporadic melanoma development. Samples in which potentially contributing variants have been detected are being sequenced in an orthogonal platform for variant confirmation.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-14T15:29:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001965","title":"Synthetic_lethality_of_TSG_in_hiPSC","description":"We are performing CRISPR drop-out screenings using Yusa's KO library in human induced pluripotent stem cell lines knock out for a list of tumor suppressor genes. We collect cell pellets at multiple time points along the screening.","abstract":"Tumor suppressor genes account for the majority of cancer drivers, while most approved molecular targeted therapies are directed against a small subset of the known oncogenes. Thus, there is a large uncovered space of targets that are not being exploited therapeutically and this currently remains as one of the critical challenges in genomic medicine. Importantly, drugs will rarely be able to directly re-activate a damaged gene, what makes targeting TSGs a specifically complex matter. To overcome this, targeted therapies will need to exploit the consequences of TSG loss-of function mutations and compensate them in an indirect manner. In order to achieve this, we will need a better understanding of the TSGs pathways and downstream effects of their loss. \n\nFor this purpose we have collected a panel of 30 isogenic human induced pluripotent stem (hiPS) cell lines with loss-of-function mutations in a single TSG each. First, we will perform a whole proteome analysis to identify the direct effects of TSG loss and deeply characterize its molecular consequences. Enrichment analysis using pathway and protein complexes databases will reveal which are the most significantly altered networks. Both downregulated and upregulated proteins can provide relevant insights, but the latter will already highlight potential therapeutical targets.  \nThen, we propose to perform a whole genome CRISPR screening to identify synthetic lethal pairs of the TSGs mutated in our panel of lines. The CRISPR screening will be performed in the parental cells as well as each of the targeted hiPS cell lines. The list of drop-out hits (i.e. guide RNAs lost in TSGs mutated cells but not in the parental line) will uncover candidate synthetic lethal pairs of the TSGs studied. At this point, integration with baseline proteomic data will help identify the most robust candidates and provide a way to filter the results based on specific hypotheses. This will enhance the probability of successful validation. Finally, the most interesting hits will be validated in independent clones and cancer cell lines. If there are drugs available we will try to reproduce the synthetic lethality events observed.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001966","title":"Sarcoma_cell_lines_WGS","description":"This is a project to understand the evolution of PARP inhibitor responsiveness in the derivative clell lines, LM7.","abstract":"This is a project to understand the evolution of PARP inhibitor responsiveness in the derivative clell lines, LM7.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001967","title":"FFPE_whole_genome_pilot","description":"To assess feasibility of whole genome sequencing","abstract":"To assess feasibility of whole genome sequencing and mutational signature algorithms in FFPE tissues. This would expand the possibility of genomic sequencing to archival clinical specimens collected as part of large clinical trials.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-15T15:26:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001968","title":"Metastatic_Breast_Cancer_Validation","description":"Validation of point mutations and small insertions and deletions in primary and associated metastatic breast cancer samples with matched normal tissues.","abstract":"Validation of point mutations and small insertions and deletions in primary and associated metastatic breast cancer samples with matched normal tissues.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-15T15:37:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001969","title":"Whole genome sequencing of colon organoid cultures with artificially induced oncogenic mutations","description":"Using the CRISPR-Cas9 genome editing system, various oncogenic mutations were introduced in the genome of normal adult stem cells derived from the colon. The resulting clonal cultures were subjected to whole genome sequencing. In addition, the cultures were transplanted in a mouse and the resulting primary and metastatic tumors were also subjected to whole genome sequencing. The initial bulk culture, which was used to generate the mutations, was also whole genome sequenced and served as a reference sample to filter germline variants.","abstract":"Using the CRISPR-Cas9 genome editing system, various oncogenic mutations were introduced in the genome of normal adult stem cells derived from the colon. The resulting clonal cultures were subjected to whole genome sequencing. In addition, the cultures were transplanted in a mouse and the resulting primary and metastatic tumors were also subjected to whole genome sequencing. The initial bulk culture, which was used to generate the mutations, was also whole genome sequenced and served as a reference sample to filter germline variants.","study_type":"Other","pubmed_ids":[27612425],"external_links":null,"is_released":true,"released_date":"2016-09-16T13:28:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001970","title":"Meningiomas induced by low-dose radiation are driven by structural variants and reveal an alternative cause for a mutational signature attributed to DNA-repair deficiency","description":"Radiation-induced meningiomas (Mrad) have predominantly been observed after high- dose irradiation of a usually primary malignant brain tumor and after low- dose irradiation for Tinea capitis. Here, we analyzed 20 Mrad following low- dose irradiation employing whole genome sequencing and methylation array analysis. Our results implicate oncogenic mechanisms beyond NF2 inactivation in low- dose Mrad, and demonstrate that low-dose irradiation is an alternative source of an HRR deficiency-like mutational signature.","abstract":"Radiation-induced meningiomas (Mrad) have predominantly been observed after high- dose irradiation of a usually primary malignant brain tumor and after low- dose irradiation for Tinea capitis. Here, we analyzed 20 Mrad following low- dose irradiation employing whole genome sequencing and methylation array analysis. Our results implicate oncogenic mechanisms beyond NF2 inactivation in low- dose Mrad, and demonstrate that low-dose irradiation is an alternative source of an HRR deficiency-like mutational signature.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001971","title":"In_Situ_Transcription_whole_genome_sequencing","description":"Whole genome sequencing of multifocal breast cancer regions. Intention to use this data to inform in-situ transcription analysis.","abstract":"Whole genome sequencing of multifocal breast cancer regions. Intention to use this data to inform in-situ transcription analysis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T08:44:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001972","title":"Breast_Heterogeneity_Validation","description":"Validation of subs and indels called in breast whole genome studies","abstract":"This project is designed to explore the geographical heterogeneity that exists within primary breast tumours. This information will be used to understand tumour evolution and to inform the design of clinical genomic studies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T11:12:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001973","title":"Exome sequence data for germline, primary tumor, and relapse tumor of a transformed non-Hodgkins lymphoma patient with unexpected long-time remission","description":"The patient was diagnosed with a transformed high-grade non-Hodgkin lymphoma stage III, and treated with conventional R-CHOP (Rituximab (R), Cyclophosphamide (C), Doxorubicin (H), Vincristine (O) and Prednisone (P)). Unfortunately, she suffered from severe toxicity but recovered during the following six months remission until a biopsy verified relapse. The patient refused second line combination chemotherapy, but accepted a 3 months palliation with R and Chlorambucil. Unexpectedly, she obtained continuous complete remission and is at present &gt;9 years after primary diagnosis.Molecular studies and data evaluation by principal component analysis, mutation screening,  and copy number variations of the primary and relapsed tumor, identified patterns of branched lymphoma evolution, most likely diverging from an unknown in situ follicular lymphoma.","abstract":"The patient was diagnosed with a transformed high-grade non-Hodgkin lymphoma stage III, and treated with conventional R-CHOP (Rituximab (R), Cyclophosphamide (C), Doxorubicin (H), Vincristine (O) and Prednisone (P)). Unfortunately, she suffered from severe toxicity but recovered during the following six months remission until a biopsy verified relapse. The patient refused second line combination chemotherapy, but accepted a 3 months palliation with R and Chlorambucil. Unexpectedly, she obtained continuous complete remission and is at present &gt;9 years after primary diagnosis.Molecular studies and data evaluation by principal component analysis, mutation screening,  and copy number variations of the primary and relapsed tumor, identified patterns of branched lymphoma evolution, most likely diverging from an unknown in situ follicular lymphoma.","study_type":"Other","pubmed_ids":[28097046],"external_links":null,"is_released":true,"released_date":"2016-09-20T13:41:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001974","title":"HipSci___Whole_Exome_sequencing___Alport","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Alport syndrome","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Alport syndrome","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:00:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001975","title":"HipSci___Whole_Exome_sequencing___Battens","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Battens disease","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Battens disease","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:03:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001976","title":"HipSci___Whole_Exome_sequencing___BPD","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with blood and platelet disorders","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with blood and platelet disorders","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:03:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001977","title":"HipSci___Whole_Exome_sequencing___Congenital_hyperinsulinia","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with congenital hyperinsulinia","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with congenital hyperinsulinia","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:04:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001978","title":"HipSci___Whole_Exome_sequencing___Ataxia","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with hereditary cerebral ataxia","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with hereditary cerebral ataxia","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:04:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001979","title":"HipSci___Whole_Exome_sequencing___HSP","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with hereditary spastic paraplegia","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with hereditary spastic paraplegia","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:05:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001980","title":"HipSci___Whole_Exome_sequencing___Cardiomyopathy","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with hypertrophic cardiomyopathy","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with hypertrophic cardiomyopathy","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:06:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001981","title":"HipSci___Whole_Exome_sequencing___Kabuki","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Kabuki syndrome","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Kabuki syndrome","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:08:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001982","title":"HipSci___Whole_Exome_sequencing___Macular_dystrophy","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Macular dystrophy","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Macular dystrophy","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:08:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001983","title":"HipSci___Whole_Exome_sequencing___PID","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with blood and platelet disorders","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with blood and platelet disorders","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:09:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001984","title":"HipSci___Whole_Exome_sequencing___Retinitis_Pigmentosa","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Retinitis Pigmentosa","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Retinitis Pigmentosa","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:10:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001985","title":"HipSci___Whole_Exome_sequencing___Usher syndrome and congenital eye defects","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Usher syndrome and congenital eye defects.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Usher syndrome and congenital eye defects.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:11:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001986","title":"HipSci_RNASEQ_Alport","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Alport syndrome patients.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Alport syndrome patients","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:16:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001987","title":"HipSci_RNASEQ_Battens","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Battens  patients.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Battens patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:16:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001988","title":"HipSci_RNASEQ_Congenital_hyperinsulinia","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Congenital hyperinsulinia  patients.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Congenital hyperinsulinia patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:17:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001989","title":"HipSci_RNASEQ_Kabuki","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from kabuki patients","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Kabuki patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:17:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001990","title":"HipSci_RNASEQ_PID","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Platelet and bleeding disorders patients","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from platelet and bleeding disorder patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:18:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001991","title":"HipSci_RNASEQ_Spastic_paraplegia","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Spastic paraplegia patients","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Spastic paraplegia patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:18:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001992","title":"HipSci_RNASEQ_Ataxia","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from hereditary cerebral ataxia  patients.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from hereditary cerebral ataxia patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:18:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001993","title":"HipSci_RNASEQ_BPD","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Blood platelet disorders  patients.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from blood platelet disorders patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:19:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001994","title":"HipSci_RNASEQ_Hypertrophic_Cardiomyopathy","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Hypertrophic Cardiomyopathy       patients.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Hypertrophic Cardiomyopathy patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:19:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001995","title":"HipSci_RNASEQ_Macular_Dystrophy","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Macular Dystrophy patients","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Macular Dystrophy patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:19:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001996","title":"HipSci_RNASEQ_Retinitis_Pigmentosa","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Retinitis Pigmentosa patients","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Retinitis Pigmentosa patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:20:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001997","title":"HipSci_RNASEQ_Usher syndrome and congenital eye defects","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Usher syndrome and congenital eye defects.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Usher syndrome and congenital eye defects.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-20T14:20:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001001998","title":"VaccGene: Identifying the genetic determinants of vaccine response","description":"It is estimated that up to 70% of the variability in response to some vaccines administered in childhood is inherited but the identification of the genetic factors responsible for this variation has not yet been prioritised. We have set-up one of the largest genome-wide association studies of vaccine responses ever undertaken, which will provide unparalleled power to identify the genetic factors associated with the response to all of the most commonly used childhood vaccines worldwide. The study includes various cohorts from Burkina Faso, Uganda, South Africa and Bangladesh genotyped of different array platforms.The results from this large-scale analysis are used to understand why HLA is strongly associated with some, but not all, toxoid vaccine responses and to identify the other elements of the immune system associated with inter-individual variability to response to multiple vaccines. These results may have important implications for future vaccine design.","abstract":"It is estimated that up to 70% of the variability in response to some vaccines administered in childhood is inherited but the identification of the genetic factors responsible for this variation has not yet been prioritised. We have set-up one of the largest genome-wide association studies of vaccine responses ever undertaken, which will provide unparalleled power to identify the genetic factors associated with the response to all of the most commonly used childhood vaccines worldwide. The study includes various cohorts from Burkina Faso, Uganda, South Africa and Bangladesh genotyped of different array platforms.The results from this large-scale analysis are used to understand why HLA is strongly associated with some, but not all, toxoid vaccine responses and to identify the other elements of the immune system associated with inter-individual variability to response to multiple vaccines. These results may have important implications for future vaccine design.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001001999","title":"HipSci___Whole_Exome_sequencing___Childhood_neurology","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Childhood neurology","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Childhood neurology","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002000","title":"HipSci___Whole_Exome_sequencing___Pulmonary_arterial_hypertension","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Pulmonary arterial hypertension","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform whole exome sequencing using Agilent whole exome pulldown method on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Pulmonary arterial hypertension","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002001","title":"HipSci_RNASEQ_Pulmonary_arterial_hypertension","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Pulmonary arterial hypertension patients\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Pulmonary arterial hypertension patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002002","title":"HipSci_RNASEQ_Childhood_neurology","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Childhood neurology patients\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from Childhood neurology patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002003","title":"Phenotype_features_in_neural_differentiation","description":"To characterise phenotypic features in neural differentiation from iPS cells","abstract":"To characterise phenotypic features in neural differentiation from iPS cells","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002004","title":"15x_WGS_GREENLAND","description":"15x whole genome sequencing in samples from the Inuit isolated sample collection in Greenland","abstract":"15x whole genome sequencing in samples from the Inuit isolated sample collection in Greenland","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002005","title":"HipSci HumanExome BeadChip analysis - Hereditary Cerebellar Ataxias","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Hereditary Cerebellar Ataxias.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Hereditary Cerebellar Ataxias.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T13:03:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002006","title":"HipSci HumanExome BeadChip analysis - Hereditary Spastic Paraplegia","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Hereditary Spastic Paraplegia.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Hereditary Spastic Paraplegia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T13:05:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002007","title":"HipSci HumanExome BeadChip analysis - Kabuki syndrome","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Kabuki syndrome.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Kabuki syndrome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T13:06:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002008","title":"HipSci HumanExome BeadChip analysis - Usher syndrome and congenital eye defects","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Usher syndrome and congenital eye defects.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Usher syndrome and congenital eye defects.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T13:06:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002009","title":"HipSci HumanExome BeadChip analysis - Alport Syndrome","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Alport Syndrome.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Alport Syndrome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T13:09:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002010","title":"HipSci HumanExome BeadChip analysis - Congenital Hyperinsulinia","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Congenital Hyperinsulinia.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Congenital Hyperinsulinia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T13:10:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002011","title":"HipSci HumanExome BeadChip analysis - Hypertrophic Cardiomyopathy","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Hypertrophic Cardiomyopathy.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Hypertrophic Cardiomyopathy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T13:10:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002012","title":"HipSci HumanExome BeadChip analysis - Primary immune deficiency","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Primary immune deficiency.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Primary immune deficiency.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T13:12:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002013","title":"HipSci HumanExome BeadChip analysis - Bleeding and Platelet disorders","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bleeding and Platelet disorders.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bleeding and Platelet disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T13:12:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002014","title":"HipSci HumanExome BeadChip analysis - Macular Dystrophy","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Macular Dystrophy.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Macular Dystrophy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T13:13:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002015","title":"HipSci HumanExome BeadChip analysis - Retinitis Pigmentosa","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Retinitis Pigmentosa.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Retinitis Pigmentosa.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T13:20:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002016","title":"HipSci HumanExome BeadChip analysis  - Battens disease","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Battens disease.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Battens disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T13:21:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002017","title":"HipSci HumanExome BeadChip analysis - Childhood neurology","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Childhood neurology.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Childhood neurology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002018","title":"HipSci HumanExome BeadChip analysis - Pulmonary arterial hypertension","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Pulmonary arterial hypertension.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Pulmonary arterial hypertension.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002019","title":"HipSci HumanExome BeadChip analysis - Alport syndrome (Manchester)","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Alport syndrome (Manchester Uni).","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Genotyping analysis using the Infinium HumanExome BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Alport syndrome (Manchester Uni).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002020","title":"HipSci HumanHT 12 Expression BeadChip analysis - Hereditary Cerebellar Ataxias","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Hereditary Cerebellar Ataxias.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Hereditary Cerebellar Ataxias.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T14:19:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002021","title":"HipSci HumanHT 12 Expression BeadChip analysis - Hereditary Spastic Paraplegia","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Hereditary Spastic Paraplegia.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Hereditary Spastic Paraplegia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T14:21:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002022","title":"HipSci HumanHT 12 Expression BeadChip analysis - Kabuki syndrome","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Kabuki syndrome.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Kabuki syndrome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T14:21:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002023","title":"HipSci HumanHT 12 Expression BeadChip analysis - Usher syndrome and congenital eye defects","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Usher syndrome and congenital eye defects.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Usher syndrome and congenital eye defects.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T14:22:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002024","title":"HipSci HumanHT 12 Expression BeadChip analysis - Alport syndrome","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Alport syndrome.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Alport syndrome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T14:24:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002025","title":"HipSci HumanHT 12 Expression BeadChip analysis - Congenital Hyperinsulinia","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Congenital Hyperinsulinia.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Congenital Hyperinsulinia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T14:26:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002026","title":"HipSci HumanHT 12 Expression BeadChip analysis - Hypertrophic Cardiomyopathy","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Hypertrophic Cardiomyopathy.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Hypertrophic Cardiomyopathy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T14:26:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002027","title":"HipSci HumanHT 12 Expression BeadChip analysis - Primary immune deficiency","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Primary immune deficiency.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Primary immune deficiency.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T14:27:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002028","title":"HipSci HumanHT 12 Expression BeadChip analysis - Bleeding and Platelet disorders","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bleeding and Platelet disorders.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bleeding and Platelet disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T14:28:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002029","title":"HipSci HumanHT 12 Expression BeadChip analysis - Macular Dystrophy","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Macular Dystrophy.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Macular Dystrophy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T14:28:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002030","title":"HipSci HumanHT 12 Expression BeadChip analysis - Retinitis Pigmentosa","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Retinitis Pigmentosa.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Retinitis Pigmentosa.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T14:29:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002031","title":"HipSci HumanHT 12 Expression BeadChip analysis - Battens disease","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Battens disease.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Battens disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-23T14:30:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002032","title":"HipSci HumanHT 12 Expression BeadChip analysis - Childhood neurology","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Childhood neurology.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Childhood neurology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002033","title":"HipSci HumanHT 12 Expression BeadChip analysis - Pulmonary arterial hypertension","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Pulmonary arterial hypertension.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Expression analysis using the Illumina HumanHT -12 Expression BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Pulmonary arterial hypertension.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002034","title":"HipSci Illumina Methylation analysis - Hereditary Cerebellar Ataxias","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Hereditary Cerebellar Ataxias.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Hereditary Cerebellar Ataxias.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002035","title":"HipSci Illumina Methylation analysis - Hereditary Spastic Paraplegia","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Hereditary Spastic Paraplegia.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Hereditary Spastic Paraplegia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002036","title":"HipSci Illumina Methylation analysis - Kabuki syndrome","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Kabuki syndrome.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Kabuki syndrome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002037","title":"HipSci Illumina Methylation analysis - Usher syndrome and congenital eye defects","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Usher syndrome and congenital eye defects.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Usher syndrome and congenital eye defects.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002038","title":"HipSci Illumina Methylation analysis - Alport syndrome","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Alport syndrome.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Alport syndrome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002039","title":"HipSci Illumina Methylation analysis - Congenital Hyperinsulinia","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Congenital Hyperinsulinia.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Congenital Hyperinsulinia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002040","title":"HipSci Illumina Methylation analysis - Hypertrophic Cardiomyopathy","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with  Hypertrophic Cardiomyopathy.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with  Hypertrophic Cardiomyopathy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002041","title":"HipSci Illumina Methylation analysis - Primary immune deficiency","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Primary immune deficiency.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Primary immune deficiency.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002042","title":"HipSci Illumina Methylation analysis - Bleeding and Platelet disorders","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bleeding and Platelet disorders.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bleeding and Platelet disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002043","title":"HipSci Illumina Methylation analysis - Macular Dystrophy","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Macular Dystrophy.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Macular Dystrophy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002044","title":"HipSci Illumina Methylation analysis - Retinitis Pigmentosa","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Retinitis Pigmentosa.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Retinitis Pigmentosa.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002045","title":"HipSci Illumina Methylation analysis - Battens disease","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Battens disease.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Battens disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002046","title":"HipSci Illumina Methylation analysis - Childhood neurology","description":"biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Childhood neurology.","abstract":"biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Childhood neurology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002047","title":"HipSci Illumina Methylation analysis - Pulmonary arterial hypertension","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Pulmonary arterial hypertension.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we performed Methylation analysis using the Infinium Methylation BeadChip on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Pulmonary arterial hypertension.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002048","title":"Familial Genome Study of IPEX-like Disease","description":"We sequenced four peripheral blood samples of a patient, sister, and both parents.","abstract":"We sequenced four peripheral blood samples of a patient, sister, and both parents.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002049","title":"Prognostic relevance of microenvironmental factors CD163 and CD8 combined with EZH2 and chromosome 18 gain in a validation cohort of follicular lymphoma patients of the Lunenburg Lymphoma Biomarker Consortium","description":"Background: In follicular lymphoma (FL), studies addressing the prognostic value of microenvironment-related immunohistochemical (IHC) markers and tumor cell-related genetic markers have yielded conflicting results, precluding implementation in practice. Therefore, the Lunenburg Lymphoma Biomarker Consortium (LLBC) performed a validation study for published markers. Methods: To maximize sensitivity, an end-of-spectrum design was applied for 122 uniformly immunochemotherapy-treated FL patients retrieved from international trials and registries; early failure (EF): progression or lymphoma-related death &lt;2 years versus long remission: response duration of &gt;5 years. IHC staining for T-cells and macrophages was performed on tissue microarrays from initial biopsy and scored with a validated computer-assisted protocol. Shallow whole-genome and deep targeted sequencing was performed on the same samples.  Results: 96/122 cases with complete molecular and immunohistochemical data were included in the analysis. EZH2 wild-type (p=0.006), gain of chromosome 18 (p=0.002), low percentages of CD8+ cells (p=0.011) and CD163+ areas (p=0.038) were associated with EF. No significant differences in other markers were observed, thereby refuting previous claims on their prognostic significance.  Conclusion: Using an optimized study design, this LLBC study validates wild-type EZH2 status, gain of chromosome 18, low percentages of CD8+ cells and CD163+ area as predictors of EF to immunochemotherapy in FL.","abstract":"Background: In follicular lymphoma (FL), studies addressing the prognostic value of microenvironment-related immunohistochemical (IHC) markers and tumor cell-related genetic markers have yielded conflicting results, precluding implementation in practice. Therefore, the Lunenburg Lymphoma Biomarker Consortium (LLBC) performed a validation study for published markers. Methods: To maximize sensitivity, an end-of-spectrum design was applied for 122 uniformly immunochemotherapy-treated FL patients retrieved from international trials and registries; early failure (EF): progression or lymphoma-related death &lt;2 years versus long remission: response duration of &gt;5 years. IHC staining for T-cells and macrophages was performed on tissue microarrays from initial biopsy and scored with a validated computer-assisted protocol. Shallow whole-genome and deep targeted sequencing was performed on the same samples.  Results: 96/122 cases with complete molecular and immunohistochemical data were included in the analysis. EZH2 wild-type (p=0.006), gain of chromosome 18 (p=0.002), low percentages of CD8+ cells (p=0.011) and CD163+ areas (p=0.038) were associated with EF. No significant differences in other markers were observed, thereby refuting previous claims on their prognostic significance.  Conclusion: Using an optimized study design, this LLBC study validates wild-type EZH2 status, gain of chromosome 18, low percentages of CD8+ cells and CD163+ area as predictors of EF to immunochemotherapy in FL.","study_type":"Other","pubmed_ids":[28411252],"external_links":null,"is_released":true,"released_date":"2016-09-27T14:44:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002050","title":"WES used for direct identification of clinically relevant neoepitopes presented on native human melanoma tissue by mass spectrometry","description":"We performed whole exome sequencing of tumor- as well as PBMC-derived DNA of five melanoma patients for identification of naturally presented patient-specific neoepitopes.","abstract":"We performed whole exome sequencing of tumor- as well as PBMC-derived DNA of five melanoma patients for identification of naturally presented patient-specific neoepitopes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-27T15:42:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002051","title":"H034. Mutational Landscape of Colorectal Cancer Liver Metastases","description":"Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality worldwide and remains the fourth common cause of death from cancer. Although significant progress has been made in the treatment of metastatic CRC, the 5-year survival remains &lt;12.5%, highlighting the urgent need for the development of new treatment approaches.Studies have shown that a high density of tumor-infiltrating lymphocytes (TILs) is correlated with better clinical outcome in patients with various cancers. These studies have also suggested that a high density of TILs is correlated with mutational load. One hypothesis in this context is that somatic mutations found in cancer cells may give rise to novel epitopes, so called neoepitopes, that attract and keep lymphocytes at the tumor site. It was also reported that cancers with a high mutational load respond best to checkpoint therapy, presumably due to neoepitopes  that can be targeted by T cells once they are released from inhibitory signals. One aim of this study was to analyze the correlation of the number of mutations and neoepitopes with lymphocyte infiltration at the invasive margin of CRC liver metastases, as this has not been systematically analyzed before. For this, we collected CRC liver metastases from a cohort of patients and selected 10 patients with high densities of infiltrating lymphocytes (TIL-high) and 10 patients with low densities (TIL-low). The two subgroups of samples were analyzed in a comparative manner for somatic mutations and neoepitopes.","abstract":"Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality worldwide and remains the fourth common cause of death from cancer. Although significant progress has been made in the treatment of metastatic CRC, the 5-year survival remains &lt;12.5%, highlighting the urgent need for the development of new treatment approaches.Studies have shown that a high density of tumor-infiltrating lymphocytes (TILs) is correlated with better clinical outcome in patients with various cancers. These studies have also suggested that a high density of TILs is correlated with mutational load. One hypothesis in this context is that somatic mutations found in cancer cells may give rise to novel epitopes, so called neoepitopes, that attract and keep lymphocytes at the tumor site. It was also reported that cancers with a high mutational load respond best to checkpoint therapy, presumably due to neoepitopes  that can be targeted by T cells once they are released from inhibitory signals. One aim of this study was to analyze the correlation of the number of mutations and neoepitopes with lymphocyte infiltration at the invasive margin of CRC liver metastases, as this has not been systematically analyzed before. For this, we collected CRC liver metastases from a cohort of patients and selected 10 patients with high densities of infiltrating lymphocytes (TIL-high) and 10 patients with low densities (TIL-low). The two subgroups of samples were analyzed in a comparative manner for somatic mutations and neoepitopes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002052","title":"Genome-Wide Association Study of aspirin-induced PUD in a UK cohort","description":"Aspirin is a widely prescribed non-steroidal anti-inflammatory drug used as an effective analgesic and at low doses as anti-platelet drug for the prevention of cardiovascular diseases.  However, aspirin is associated with a significant incidence of upper gastrointestinal (GI) complications, notably peptic ulceration.  This study aims to identify genetic risk factors associated with the pathogenesis of aspirin-induced upper GI ulceration.A cohort of 248 patients with aspirin-induced, endoscopiclly confirmed GI ulceration and 491 controls (ulcer, without aspirin or aspirin without ulcer) were genotyped for 1.524,956 SNPs using the Illumina Omni 2.5 SNP array.  A replication cohort (206 NSAID-induced ulcer cases [of which 87 were aspirin] and 309 controls) was subsequently genotyped for identified SNP association signals using Sequenom iPLEX Massarry.  Logistic regression analysis of identified two SNP signal with suggestive association with aspirin-induced GI ulceration.  A SNP within the EYA1 locus (rs12678747) was found to be associated with aspirin GI ulceration in both the discovery cohort (p=3.79x10-7, OR=2.06 ([1.55-2.73]) and, to a lesser extent, in the replication cohort (p=.0005, OR=1.71[1.17-2.50].  Combined analysis of both cohorts yielded a genome wide significant association (p=1.46x10-8). The rs12678747 genotype was found to be associated with significantly higher EYA1 transcript in ulcer biopsy tissue (p&lt;0.05).Data suggest that EYA1 may represent a risk locus for aspirin-induced GI ulceration.  Though it is thought that EYA1 may play a key role in mediating cell death/ survival","abstract":"Aspirin is a widely prescribed non-steroidal anti-inflammatory drug used as an effective analgesic and at low doses as anti-platelet drug for the prevention of cardiovascular diseases.  However, aspirin is associated with a significant incidence of upper gastrointestinal (GI) complications, notably peptic ulceration.  This study aims to identify genetic risk factors associated with the pathogenesis of aspirin-induced upper GI ulceration.A cohort of 248 patients with aspirin-induced, endoscopiclly confirmed GI ulceration and 491 controls (ulcer, without aspirin or aspirin without ulcer) were genotyped for 1.524,956 SNPs using the Illumina Omni 2.5 SNP array.  A replication cohort (206 NSAID-induced ulcer cases [of which 87 were aspirin] and 309 controls) was subsequently genotyped for identified SNP association signals using Sequenom iPLEX Massarry.  Logistic regression analysis of identified two SNP signal with suggestive association with aspirin-induced GI ulceration.  A SNP within the EYA1 locus (rs12678747) was found to be associated with aspirin GI ulceration in both the discovery cohort (p=3.79x10-7, OR=2.06 ([1.55-2.73]) and, to a lesser extent, in the replication cohort (p=.0005, OR=1.71[1.17-2.50].  Combined analysis of both cohorts yielded a genome wide significant association (p=1.46x10-8). The rs12678747 genotype was found to be associated with significantly higher EYA1 transcript in ulcer biopsy tissue (p&lt;0.05).Data suggest that EYA1 may represent a risk locus for aspirin-induced GI ulceration.  Though it is thought that EYA1 may play a key role in mediating cell death/ survival","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-29T18:22:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002053","title":"Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis","description":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","abstract":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002054","title":"The BC Cancer Agency's Personalized Onco-Genomics Project","description":"The BC Cancer Agency's Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","abstract":"The BC Cancer Agency's Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002055","title":"2016_09_30_11_22_30_851_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002057","title":"Characterization_of_genomic_landscape_of_Peripheral_T_cell_Lymphomas__not_otherwise_specified__PTCL_NOS_","description":"Peripheral T-cell lymphomas not otherwise specified (PTCL-NOS) represent a heterogeneous group of nodal and extra-nodal mature T-cell lymphomas, with a low prevalence in Western countries. PTCL-NOSs account for about 25% of all PTCLs and are currently diagnosed based on exclusion criteria, as this lymphomas lack unifying morphological, phenotypic and genomic features. Cytogenetic and FISH analysis of PTCL-NOS samples have not revealed recurrent pathogenetic abnormalities, while gene expression profiling has shown only partial ability to segregate cases representing homogeneous clinic-pathological entities. This underscores the need to look at PTCL-NOS with innovative and high-throughput approaches to identify recurrent genetic lesions that could further our understanding of the biology of this heterogeneous group of diseases, provide better diagnostic tools and perhaps new targets for innovative treatments.\nOur aim is to study ~15 patients affected by PTCL-NOS. Out study will be funded by a private, non-profit Italian cancer research fund (Associazione Italiana per la Ricerca sul Cancro, www.airc.it) based on a grant owned by Anna Dodero and Cristiana Carniti, hematologists at INT.\nSamples will be analysed by whole genome sequencing using Illumina X10 machines, on a 150bp-PE protocol. Data will be analysed using the pipeline available in Team 78, under the supervision of Peter Campbell, the WTSI faculty who will oversee the project, and by Francesco Maura, visiting scientist at the WTSI.","abstract":"Peripheral T-cell lymphomas not otherwise specified (PTCL-NOS) represent a heterogeneous group of nodal and extra-nodal mature T-cell lymphomas, with a low prevalence in Western countries. PTCL-NOSs account for about 25% of all PTCLs and are currently diagnosed based on exclusion criteria, as this lymphomas lack unifying morphological, phenotypic and genomic features. In this project We will sequence by whole genome sequencing ~15 cases of PTCL-NOS form formal-fixed paraffin-embedded samples available at INT along with matched normal DNA from the same patient. All data will be analysed by Sanger Team 78 standard pipeline in order to describe for the first time the global genomic landscape of this lymphoma. Including few patients with multiple samples collected at different time points we will be able to evidence for the first time the PTCL-NOS genomic evolution and the treatment resistance mechanisms.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-09-30T13:58:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002058","title":"PTCV600E: desmoplasia and complex microvolumes","description":"Although 60% of papillary thyroid carcinomas are BRAFV600E mutant (PTCV600E), the higher aggressiveness of these cancers is still debated. We analyzed 364 PTCs from The Cancer Genome Atlas (TCGA), including 211 PTCV600E; stained 22 independent PTC for BRAFV600E and Ki67; sequenced the exomes and stained BRAFV600E in 5 primary tumor blocks and 4 nodal metastases from one PTCV600E patient; and reconstructed the 3D volumes of one tumor and one metastatic blocks at histological resolution. In TCGA BRAFV600E was associated with higher expression of proliferation markers and lower expression of thyroid differentiation markers, independently of tumor purity. Moreover, PTCV600E, in line with their overall lower purity, also had higher expression of fibroblast- and T-cell-associated genes, and presented more fibrosis. Tumor cells that appeared disconnected on 2D histological slices revealed to be part of a unique tumor component in the 3D reconstructed microvolumes, and formed a surprisingly complex connected space, infiltrating a proliferative stroma. Finally, in our PTC set, both stromal fibroblasts and tumor cells presented higher proliferation rates in PTCV600E. Our results support increased aggressiveness associated with BRAFV600E in PTC, and shed light on the important role of the stroma in tumor expansion. The concept of invasive front breaks down in the uncovered 3D morphology, as all tumor cells were within short distance or in contact with the stroma. The greater and more active fibrotic component could explain why BRAF inhibitors have proven less efficient in thyroid cancers and predict better efficiency of combined targeted treatments, as previously proposed for melanomaV600E.","abstract":"Although 60% of papillary thyroid carcinomas are BRAFV600E mutant (PTCV600E), the higher aggressiveness of these cancers is still debated. We analyzed 364 PTCs from The Cancer Genome Atlas (TCGA), including 211 PTCV600E; stained 22 independent PTC for BRAFV600E and Ki67; sequenced the exomes and stained BRAFV600E in 5 primary tumor blocks and 4 nodal metastases from one PTCV600E patient; and reconstructed the 3D volumes of one tumor and one metastatic blocks at histological resolution. In TCGA BRAFV600E was associated with higher expression of proliferation markers and lower expression of thyroid differentiation markers, independently of tumor purity. Moreover, PTCV600E, in line with their overall lower purity, also had higher expression of fibroblast- and T-cell-associated genes, and presented more fibrosis. Tumor cells that appeared disconnected on 2D histological slices revealed to be part of a unique tumor component in the 3D reconstructed microvolumes, and formed a surprisingly complex connected space, infiltrating a proliferative stroma. Finally, in our PTC set, both stromal fibroblasts and tumor cells presented higher proliferation rates in PTCV600E. Our results support increased aggressiveness associated with BRAFV600E in PTC, and shed light on the important role of the stroma in tumor expansion. The concept of invasive front breaks down in the uncovered 3D morphology, as all tumor cells were within short distance or in contact with the stroma. The greater and more active fibrotic component could explain why BRAF inhibitors have proven less efficient in thyroid cancers and predict better efficiency of combined targeted treatments, as previously proposed for melanomaV600E.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002059","title":"Exome_sequencing_of_a_cohort_of_Rett_syndromelike_patients","description":"The aim of the project is the definition of the molecular defect in a cohort of Rett-like patients negative for  mutations in known disease genes.  To this aim, a number of unrelated trios (patients plus parents) will be analysed by exome sequencing.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The aim of the project is the definition of the molecular defect in a cohort of Rett-like patients negative for  mutations in known disease genes.  To this aim, a number of unrelated trios (patients plus parents) will be analysed by exome sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-03T14:03:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002060","title":"A_compendium_of_mutational_signatures_due_to_environmental_exposures","description":"Analysis of mutational signatures caused by exposure to known mutagens in human induced pluripotent stem (iPS) cells. A reference human iPS cell-line will be exposed to 100 chemicals known or proposed to be mutagenic. Following exposure to mutagen, cells will undergo a period of recovery before sub clones are generated and sequenced. The progenitor “parental” IPS cell-line will be used to generate reference sequence data, in order to determine the mutational signatures acquired as a result of exposure to different mutagens.","abstract":"Analysis of mutational signatures caused by exposure to known mutagens in human induced pluripotent stem (iPS) cells. A reference human iPS cell-line will be exposed to 100 chemicals known or proposed to be mutagenic. Following exposure to mutagen, cells will undergo a period of recovery before sub clones are generated and sequenced. The progenitor “parental” IPS cell-line will be used to generate reference sequence data, in order to determine the mutational signatures acquired as a result of exposure to different mutagens.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-03T14:14:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002061","title":"TBA","description":"Analysis of mutational signatures arising in vivo in humans. iPS cells from control patients and\n100 patients carrying known mutations in DNA repair/editing genes will be generated, and\nsequenced.Blood from the patients will also be used to generate reference 'germline' sequence data.","abstract":"Insignia aims to gain a better understanding of the underlying sources of mutagenesis, through studying the mutation landscape in patients with known defects in DNA repair. In this study we have performed ChIP-seq for H3K4me3, H3K27ac and H3K27me3 on induced pluripotent stem (iPS) cells derived from the blood of DNA repair deficient patients and control donors.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002062","title":"TBA","description":"Analysis of mutational signatures arising in vivo in humans. iPS cells from control patients and\n100 patients carrying known mutations in DNA repair/editing genes will be generated, and\nsequenced.Blood from the patients will also be used to generate reference 'germline' sequence data.","abstract":"Insignia aims to gain a better understanding of the underlying sources of mutagenesis, through studying the mutation landscape in patients with known defects in DNA repair. In this study we have performed RNA-seq on induced pluripotent stem (iPS) cells derived from the blood of DNA repair deficient patients and control donors. RNA was purified from the iPS cells using the Qiagen AllPrep® DNA/RNA/miRNA Universal Kit on the QIAcube®.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002063","title":"Mutational_signatures_of_DNA_damage_and_repair_processes","description":"Analysis of mutational signatures arising in vivo in humans. iPS cells from control patients and 100 patients carrying known mutations in DNA repair/editing genes will be generated, and sequenced. Blood from the patients will also be used to generate reference 'germline' sequence data.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"DNA in all cells is prone to mutagenesis, with somatic mutations making key contributions to\nvarious human diseases such as cancer, and to aging itself. Mutations may be the\nconsequence of exogenous or endogenous mutagenic influences (including radiations and\nDNA-damaging chemicals), and also result from the intrinsic infidelity of DNA replication or\nenzymatic DNA modifications. Somatic mutations are generally mitigated by the cellular DNA\nrepair machinery, and defective functioning of components of this machinery can markedly\nincrease mutation rates. Different mutational processes leave different, characteristic\nsignatures of somatic mutations on the exposed cellular genome. Notably, recent analyses of\ncancer genomes have revealed several novel mutational signatures, the biological bases of\nwhich are predominantly unknown. To generally elucidate somatic mutational processes\noperative in cells, in particular their influences on human disease, we propose to\nsystematically survey the mutational signatures generated by exposures to known DNA\ndamaging agents and defective DNA repair/editing processes. These studies will provide a\nseries of mutational signatures with known underlying causes for subsequent matching to\nsignatures found in normal or diseased human cells, and will explore how various cellular\ncomponents influence mutagenesis. \n\nA “mutational signature” is the pattern of mutations occurring as a consequence of unfaithful\nDNA replication, or as a result of an exposure to an endogenous or environmental mutagen.\nMutational signatures include one or more classes of DNA change; base substitutions,\ninsertions and deletions, rearrangements and copy number changes. They can be given extra\ndiscriminatory power by further characterisation of each mutation class; for example, for base\nsubstitutions, by incorporating the subclass, the sequence context, the transcriptional strand,\nevidence of substitution clustering (kataegis) and other features relating to the genomic or\nepigenomic landscape.\n\nMutational signatures extracted in this proposal will all be characterised by next generation\nsequencing of whole genomes of cell clones that have been exposed to a mutational process\ncaused by DNA damaging agents or abnormalities in DNA repair/editing.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002064","title":"Identification_of_genes_involved_in_congenital_disorders_of_glycosylation_and_3_methylglutaconic_aciduria","description":"Identification of genes involved in congenital disorders of glycosylation and 3-methylglutaconic aciduria.\nThere are more than 100 genes known for congenital disorders of glycosylation and new disorders are discovered each year.  WE included patients with a so far unsolved glycosylation disease.\nThe diagnostic group 3-methyglutaconic aciduria is a heterogenous group of disorders mostly caused by abnormal phospholipid synthesis or in association with mitochondrial dysfunction.  We included patients with a so far unsolved disease and 3-methylglutaconic aciduria.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Identification of genes involved in congenital disorders of glycosylation and 3-methylglutaconic aciduria.\nThere are more than 100 genes known for congenital disorders of glycosylation and new disorders are discovered each year.  WE included patients with a so far unsolved glycosylation disease.\nThe diagnostic group 3-methyglutaconic aciduria is a heterogenous group of disorders mostly caused by abnormal phospholipid synthesis or in association with mitochondrial dysfunction.  We included patients with a so far unsolved disease and 3-methylglutaconic aciduria.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-03T15:48:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002065","title":"Similarity and diversity of the tumor microenvironment in multiple metastases: critical implications for overall and progression-free survival of high-grade serous ovarian cancer.","description":"The tumor microenvironment is pivotal in influencing cancer progression and metastasis. Different cells co-exist with high spatial diversity within a patient, yet their combinatorial effects are poorly understood. We investigate the similarity of the tumor microenvironment of 192 local metastatic lesions in 61 ovarian cancer patients. An ecologically inspired measure of microenvironmental diversity derived from multiple metastasis sites is correlated with clinicopathological characteristics and prognostic outcome. We demonstrate a high accuracy of our automated analysis across multiple sites. A low level of similarity in microenvironmental composition is observed between ovary tumor and corresponding local metastases (stromal ratio r = 0.30, lymphocyte ratio r = 0.37). We identify a new measure of microenvironmental diversity derived from Shannon entropy that is highly predictive of poor overall (p = 0.002, HR = 3.18, 95% CI = 1.51-6.68) and progression-free survival (p = 0.0036, HR = 2.83, 95% CI = 1.41-5.7), independent of and stronger than clinical variables, subtype stratifications based on single cell types alone and number of sites. Although stromal influence in ovary tumors is known to have significant clinical implications, our findings reveal an even stronger impact orchestrated by diverse cell types. Quantitative histology-based measures can further enable objective selection of patients who are in urgent need of new therapeutic strategies such as combinatorial treatments targeting heterogeneous tumor microenvironment.","abstract":"The tumor microenvironment is pivotal in influencing cancer progression and metastasis. Different cells co-exist with high spatial diversity within a patient, yet their combinatorial effects are poorly understood. We investigate the similarity of the tumor microenvironment of 192 local metastatic lesions in 61 ovarian cancer patients. An ecologically inspired measure of microenvironmental diversity derived from multiple metastasis sites is correlated with clinicopathological characteristics and prognostic outcome. We demonstrate a high accuracy of our automated analysis across multiple sites. A low level of similarity in microenvironmental composition is observed between ovary tumor and corresponding local metastases (stromal ratio r = 0.30, lymphocyte ratio r = 0.37). We identify a new measure of microenvironmental diversity derived from Shannon entropy that is highly predictive of poor overall (p = 0.002, HR = 3.18, 95% CI = 1.51-6.68) and progression-free survival (p = 0.0036, HR = 2.83, 95% CI = 1.41-5.7), independent of and stronger than clinical variables, subtype stratifications based on single cell types alone and number of sites. Although stromal influence in ovary tumors is known to have significant clinical implications, our findings reveal an even stronger impact orchestrated by diverse cell types. Quantitative histology-based measures can further enable objective selection of patients who are in urgent need of new therapeutic strategies such as combinatorial treatments targeting heterogeneous tumor microenvironment.","study_type":"Other","pubmed_ids":[27661102],"external_links":null,"is_released":true,"released_date":"2016-10-03T16:08:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002066","title":"Pan-cancer analysis of somatic copy number alterations implicates IRS4 and IGF2 in enhancer hijacking","description":"Extensive prior research has focused on somatic copy-number alterations (SCNAs) affecting cancer genes, yet the extent to which recurrent SCNAs exert their influence through rearranging cis-regulatory elements remains unclear. Here, we present a framework for inferring cancer-related gene overexpression resulting from cis-regulatory element reorganization (e.g., enhancer hijacking), by integrating SCNAs, gene expression data, and information on chromatin interaction domains. Analysis of 7,416 cancer genomes uncovered several pan-cancer candidate genes, including IRS4, SMARCA1 and TERT. We demonstrate that IRS4 overexpression in lung cancer associates with recurrent deletions in cis, and present evidence supporting a tumor-promoting role. We additionally pursued cancer type-specific analyses, uncovering IGF2 as a target for enhancer hijacking in colorectal cancer. IGF2-containing tandem duplications result in the de novo formation of a 3D contact domain comprising IGF2 and a lineage-specific super-enhancer, which mediates high-level gene activation. Our framework enables systematic inference of cis-regulatory element rearrangements mediating dysregulation in cancer.","abstract":"Extensive prior research has focused on somatic copy-number alterations (SCNAs) affecting cancer genes, yet the extent to which recurrent SCNAs exert their influence through rearranging cis-regulatory elements remains unclear. Here, we present a framework for inferring cancer-related gene overexpression resulting from cis-regulatory element reorganization (e.g., enhancer hijacking), by integrating SCNAs, gene expression data, and information on chromatin interaction domains. Analysis of 7,416 cancer genomes uncovered several pan-cancer candidate genes, including IRS4, SMARCA1 and TERT. We demonstrate that IRS4 overexpression in lung cancer associates with recurrent deletions in cis, and present evidence supporting a tumor-promoting role. We additionally pursued cancer type-specific analyses, uncovering IGF2 as a target for enhancer hijacking in colorectal cancer. IGF2-containing tandem duplications result in the de novo formation of a 3D contact domain comprising IGF2 and a lineage-specific super-enhancer, which mediates high-level gene activation. Our framework enables systematic inference of cis-regulatory element rearrangements mediating dysregulation in cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002067","title":"Whole_exome_sequencing_for_clarification_of_rare_causes_of_axonal_Charcot_Marie_Tooth_disease_","description":"The project is focused on the axonal forms of Charcot-Marie-Tooth (CMT) disease.  We have selected 13 families (7 from Spain and 6 from Czech Republic) that have been indepth clinically assessed and previously tested for mutations in known CMT genes without causal variants characterised.  In these patients we expect to discover several CMT2 genes.  Thus, we requested for exome sequencing of 45 DNAs:27 exomes in families from Spain and 18 exomes in the families from Czech Republic.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The project is focused on the axonal forms of Charcot-Marie-Tooth (CMT) disease.  We have selected 13 families (7 from Spain and 6 from Czech Republic) that have been indepth clinically assessed and previously tested for mutations in known CMT genes without causal variants characterised.  In these patients we expect to discover several CMT2 genes.  Thus, we requested for exome sequencing of 45 DNAs:27 exomes in families from Spain and 18 exomes in the families from Czech Republic.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-04T14:28:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002068","title":"Molecular_diagnosis_of_albinism","description":"Albinism is genetically heterogeneous rare genetic condition affecting 1:17000 in the Western world (but more frequent in Africa) whose main feature is a profound visual impairment, characterised by foveal hypoplasia, abnormal chiasmatic connections, nystagmus and photofobia.  All these features result in severly altered visual acuity (&lt;0,1), absent depth perception and poor night vision.  People with albinism are primarily visually handicapped.  In addition, for some types of albinism, the visual phenotype can be presented with partial or total hypopigmentation, hence resulting in a secondary phenotype which can lead to skin cancer if skin is not adequately protected.  Recently a new syndrome has been described, FHONDA, with the same visual abnormalities of albinism but without pigment alteration.  The traditional classification differentiates Oculoculatenous albinism (OCA), where hypopigmentation involves hair, skin and eyes versus Ocular Albinism (OA), where hypopigmentation only affects the eyes.  These are non-sydrimic types of albinism.  Some syndromic forms (Hermansky-Pudlak=HPS, Chediak-Higashi=CHS) affect cells beyond pigment cells, present in the lungs, immune system, platelets and intestines, resulting in more severe phenotypes that can be fatal.  Mutations in at least 19 genes are assocaited with the corresponding types of albinism.  Most hospitals will only diagnose the most frequent cases using traditional Sanger, MLPA approaches.  Some will use CGH arrays.  We aim to diagnose all cases of albinism through the Albinochip proposal, which combines a Sequenom first step of known mutations combined with subsequent NGS approaches.  In some cases we fail to find a second mutation, these are good candidates for further full exome analyses.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Albinism is genetically heterogeneous rare genetic condition affecting 1:17000 in the Western world (but more frequent in Africa) whose main feature is a profound visual impairment, characterised by foveal hypoplasia, abnormal chiasmatic connections, nystagmus and photofobia.  All these features result in severly altered visual acuity (&lt;0,1), absent depth perception and poor night vision.  People with albinism are primarily visually handicapped.  In addition, for some types of albinism, the visual phenotype can be presented with partial or total hypopigmentation, hence resulting in a secondary phenotype which can lead to skin cancer if skin is not adequately protected.  Recently a new syndrome has been described, FHONDA, with the same visual abnormalities of albinism but without pigment alteration.  The traditional classification differentiates Oculoculatenous albinism (OCA), where hypopigmentation involves hair, skin and eyes versus Ocular Albinism (OA), where hypopigmentation only affects the eyes.  These are non-sydrimic types of albinism.  Some syndromic forms (Hermansky-Pudlak=HPS, Chediak-Higashi=CHS) affect cells beyond pigment cells, present in the lungs, immune system, platelets and intestines, resulting in more severe phenotypes that can be fatal.  Mutations in at least 19 genes are assocaited with the corresponding types of albinism.  Most hospitals will only diagnose the most frequent cases using traditional Sanger, MLPA approaches.  Some will use CGH arrays.  We aim to diagnose all cases of albinism through the Albinochip proposal, which combines a Sequenom first step of known mutations combined with subsequent NGS approaches.  In some cases we fail to find a second mutation, these are good candidates for further full exome analyses.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-04T15:02:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002069","title":"MYOSEQ project","description":"The MYOSEQ project focuses on the application of next generation sequencing, in particular whole exome sequencing (WES), in a large cohort of patients with unexplained limb‐girdle weakness (LGW). Focusing on undiagnosed patients with a clearly defined clinical phenotype enables increased diagnostic rates for known genes (in particular Pompe disease, GNE related pathologies and other known LGMD subtypes) in this cohort, while the use of WES provides scope both for new gene discovery and for additional research into disease modifiers and genotype‐phenotype correlation with substantial cost effectiveness. The LGW patient cohort was collated by Newcastle University in collaboration with clinical centers across Europe. The sequencing was performed at the Broad Institute and jointly analyzed with Newcastle University.","abstract":"The MYOSEQ project focuses on the application of next generation sequencing, in particular whole exome sequencing (WES), in a large cohort of patients with unexplained limb‐girdle weakness (LGW). Focusing on undiagnosed patients with a clearly defined clinical phenotype enables increased diagnostic rates for known genes (in particular Pompe disease, GNE related pathologies and other known LGMD subtypes) in this cohort, while the use of WES provides scope both for new gene discovery and for additional research into disease modifiers and genotype‐phenotype correlation with substantial cost effectiveness. The LGW patient cohort was collated by Newcastle University in collaboration with clinical centers across Europe. The sequencing was performed at the Broad Institute and jointly analyzed with Newcastle University.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-05T15:05:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002070","title":"BLUEPRINT Hematopoietic Stem/Progenitor Cell Methylomes","description":"An optimized whole genome bisulfite sequencing protocol (µWGBS, Farlik et al. 2015 Cell Reports) was used to establish DNA methylation profiles of FACS-purified stem and progenitor cells types of the human blood lineage. Most cell types were sorted from the peripheral blood of three donors with eight pools of ten cells, two pools of 50 cells, and one pool of 1000 cells. HSCs and MPPs were also sorted from fetal liver (HSCs only), cord blood, and bone marrow. Single-cell methylomes using the scWGBS protocol (Farlik et al. 2015 Cell Reports) were established for six cell types (HSC, MPP, CMP, GMP, CLP, MLP0). Gene expression profiling using the Smart-seq2 protocol (Picelli et al. 2013 Nature Methods) was done for nine stem/progenitor cell types (HSC, MPP, CMP, GMP, CLP, MLP0, MLP1, MLP2, MLP3).","abstract":"An optimized whole genome bisulfite sequencing protocol (µWGBS, Farlik et al. 2015 Cell Reports) was used to establish DNA methylation profiles of FACS-purified stem and progenitor cells types of the human blood lineage. Most cell types were sorted from the peripheral blood of three donors with eight pools of ten cells, two pools of 50 cells, and one pool of 1000 cells. HSCs and MPPs were also sorted from fetal liver (HSCs only), cord blood, and bone marrow. Single-cell methylomes using the scWGBS protocol (Farlik et al. 2015 Cell Reports) were established for six cell types (HSC, MPP, CMP, GMP, CLP, MLP0). Gene expression profiling using the Smart-seq2 protocol (Picelli et al. 2013 Nature Methods) was done for nine stem/progenitor cell types (HSC, MPP, CMP, GMP, CLP, MLP0, MLP1, MLP2, MLP3).","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-06T21:09:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002071","title":"DNA methylation intratumor heterogeneity in localized lung adenocarcinomas","description":"Cancers are composed of cells with distinct molecular and phenotypic features within a given tumor, a phenomenon termed intratumor heterogeneity (ITH). Previously, we have demonstrated genomic ITH in localized lung adenocarcinomas; however, the nature of methylation ITH in lung cancers has not been well investigated. In this study, we generated methylation profiles of 48 spatially separated tumor regions from 11 localized lung adenocarcinomas and their matched normal lung tissues using Illumina Infinium Human Methylation 450K BeadChip array. We observed methylation ITH within the same tumors, but to a much less extent compared to inter-individual heterogeneity. On average, 25% of all differentially methylated probes compared to matched normal lung tissues were shared by all regions from the same tumors. This is in contrast to somatic mutations, of which approximately 77% were shared events amongst all regions of individual tumors, suggesting that while the majority of somatic mutations were early clonal events, the tumor-specific DNA methylation might be associated with later branched evolution of these 11 tumors. Furthermore, our data showed that a higher extent of DNA methylation ITH was associated with larger tumor size, advanced age and increased risk of postsurgical recurrence.","abstract":"Cancers are composed of cells with distinct molecular and phenotypic features within a given tumor, a phenomenon termed intratumor heterogeneity (ITH). Previously, we have demonstrated genomic ITH in localized lung adenocarcinomas; however, the nature of methylation ITH in lung cancers has not been well investigated. In this study, we generated methylation profiles of 48 spatially separated tumor regions from 11 localized lung adenocarcinomas and their matched normal lung tissues using Illumina Infinium Human Methylation 450K BeadChip array. We observed methylation ITH within the same tumors, but to a much less extent compared to inter-individual heterogeneity. On average, 25% of all differentially methylated probes compared to matched normal lung tissues were shared by all regions from the same tumors. This is in contrast to somatic mutations, of which approximately 77% were shared events amongst all regions of individual tumors, suggesting that while the majority of somatic mutations were early clonal events, the tumor-specific DNA methylation might be associated with later branched evolution of these 11 tumors. Furthermore, our data showed that a higher extent of DNA methylation ITH was associated with larger tumor size, advanced age and increased risk of postsurgical recurrence.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002072","title":"Single-cell RNA sequencing on 5063 single T cells isolated from peripheral blood, tumour and adjacent normal tissues from six hepatocellular carcinoma patients.","description":"Single-cell RNA sequencing on 5063 single T cells isolated from peripheral blood, tumour and adjacent normal tissues from six hepatocellular carcinoma patients. The transcriptional properties of these individual cells, coupled with the assembled T cell receptor (TCR) sequences, were used to delineate the molecular subtypes, lineage, and functional properties of each T cell group.\nFor five HCC patient, the exome-seq data of matched normal/tumor and bulk RNA-seq data of tumor are also available.","abstract":"Single-cell RNA sequencing on 5063 single T cells isolated from peripheral blood, tumour and adjacent normal tissues from six hepatocellular carcinoma patients. The transcriptional properties of these individual cells, coupled with the assembled T cell receptor (TCR) sequences, were used to delineate the molecular subtypes, lineage, and functional properties of each T cell group.\nFor five HCC patient, the exome-seq data of matched normal/tumor and bulk RNA-seq data of tumor are also available.","study_type":"Other","pubmed_ids":[28622514],"external_links":null,"is_released":true,"released_date":"2016-10-07T16:26:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002073","title":"Combining transcription factor binding affinities with open chromatin data for accurate gene expression prediction","description":"The binding and contribution of transcription factors (TF) to cell specific gene expression is often deduced from open-chromatin measurements to avoid cost and labour intensive TF ChIP-seq assays.It is important to develop reliable and fast computational methods for accurate TF binding prediction in open-chromatin regions (OCRs). Here, we report a novel segmentation-based method, TEPIC, to predict TF binding by combining sets of OCRs with position weight matrices.TEPIC can be applied to various open-chromatin data, e.g. DNaseI-seq and NOMe-seq, using either peaks or footprints as input.In addition to open-chromatin data, also Histone-Marks (HMs) can be used in TEPIC to identify candidate TF binding sites.TEPIC computes TF affinities and uses open-chromatin/HM signal intensity as quantitative measures of TF binding strength.Using machine learning techniques, we show that incorporating low affinity binding sites improves our ability to explain gene expression variability compared to the standard presence/absence classification of binding sites.Further, we show that both footprints and peaks capture essential TF binding events and lead to a good prediction performance.In our application, gene-based scores computed by TEPIC with one open-chromatin assay nearly reach the quality of several TF ChIP-seq datasets.Finally, we show that these scores correctly predict known transcriptional regulators as illustrated by the application to novel DNaseI-seq and NOMe-seq data for primary human hepatocytes and CD4+ T-cells, respectively.","abstract":"The binding and contribution of transcription factors (TF) to cell specific gene expression is often deduced from open-chromatin measurements to avoid cost and labour intensive TF ChIP-seq assays.It is important to develop reliable and fast computational methods for accurate TF binding prediction in open-chromatin regions (OCRs). Here, we report a novel segmentation-based method, TEPIC, to predict TF binding by combining sets of OCRs with position weight matrices.TEPIC can be applied to various open-chromatin data, e.g. DNaseI-seq and NOMe-seq, using either peaks or footprints as input.In addition to open-chromatin data, also Histone-Marks (HMs) can be used in TEPIC to identify candidate TF binding sites.TEPIC computes TF affinities and uses open-chromatin/HM signal intensity as quantitative measures of TF binding strength.Using machine learning techniques, we show that incorporating low affinity binding sites improves our ability to explain gene expression variability compared to the standard presence/absence classification of binding sites.Further, we show that both footprints and peaks capture essential TF binding events and lead to a good prediction performance.In our application, gene-based scores computed by TEPIC with one open-chromatin assay nearly reach the quality of several TF ChIP-seq datasets.Finally, we show that these scores correctly predict known transcriptional regulators as illustrated by the application to novel DNaseI-seq and NOMe-seq data for primary human hepatocytes and CD4+ T-cells, respectively.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-10T12:56:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002074","title":"Gene_Characterization_in_Carbohydrate_metabolic_alterations__neonatel_diabetes___congenital_hyperinsulinemic__in_early_childhood","description":"Whole Exome Sequencing of trios (proband + parents) or probands only with Neonatal Diabetes Mellitus (NDM) or Congenital Hyperinsulinism of Infancy (CHI) of unknown genetic origin.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Whole Exome Sequencing of trios (proband + parents) or probands only with Neonatal Diabetes Mellitus (NDM) or Congenital Hyperinsulinism of Infancy (CHI) of unknown genetic origin.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-10T14:56:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002075","title":"A mutation in VPS15 (PIK3R4) causes a ciliopathy and affects IFT20 release from the cis-Golgi","description":"VPS15 is known as a VPS34-associated protein that functions in intracellular trafficking and autophagy. Here the authors identify a role for VPS15 in cilopathy and ciliary phenotypes, and show that it interacts with GM130 and functions in IFT20-dependent cis-Golgi to cilium trafficking.","abstract":"VPS15 is known as a VPS34-associated protein that functions in intracellular trafficking and autophagy. Here the authors identify a role for VPS15 in cilopathy and ciliary phenotypes, and show that it interacts with GM130 and functions in IFT20-dependent cis-Golgi to cilium trafficking.","study_type":"Other","pubmed_ids":[27882921],"external_links":null,"is_released":true,"released_date":"2016-10-10T16:33:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002076","title":"Normal Breast Tissue Biopsy Study - Gene Expression in Normal Human Breast Tissue of Post-Menopausal Women","description":"Normal Breast Tissue Biopsy Study - Gene Expression in Normal Human Breast Tissue of Post-Menopausal Women Sanda Krum-Hansen (1), Christopher G. Fenton (2,3), Jan Ole Frantzen (4), Inger Riise Bergheim (5), Anne-Lise Børresen- Dale (5,6), Eiliv Lund (1) and Ruth H. Paulssen (2,3),       1Department of Community Medicine, UiT-The Arctic University of Norway, N-9037 Tromsø, Norway2Department of Clinical Medicine &amp; 3Genomics Support Center Tromsø (GSCT), UiT- The  Arctic University of Norway, N-9037 Tromsø, Norway4University Hospital of North Norway, Narvik Hospital, N-8516 Narvik, Norway  5Department of Cancer Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital HF, N-0310 Oslo, Norway    6Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway;     Aim:Gene expression analysis in tissue are established and valuable tools in breast cancer research. However, knowledge about variation in gene expression in normal breast tissue has not been widely explored. Surrogates for normal breast tissue vary between studies making comparisons between them difficult. There is a need to describe gene expression in normal breast tissue and its normal variation, establishing robust base line for further studies.Matherial and Methods:Using microarray technology, we analyzed a large (n=311), representative sample of breast biopsies from healthy postmenopausal women in the Norwegian Woman and Cancer study (NOWAC). We investigated gene expression variability following frequent exposures such as smoking, HRT and alcohol consumption in non-experimental conditions.Results:We observed that the overall gene expression level in normal breast tissue is low and not strongly influenced by exposure to HRT, alcohol or smoking. However, pathway analyses revealed enrichment of different gene sets between exposed and non-exposed groups indicating that these exposures are reflected in normal breast tissue. On the single gene level, Cytochrome P450 (CYP1B1) showed significant up-regulation with a fold-change of 1.36 and p&lt;0.05 in smokers.","abstract":"Normal Breast Tissue Biopsy Study - Gene Expression in Normal Human Breast Tissue of Post-Menopausal Women Sanda Krum-Hansen (1), Christopher G. Fenton (2,3), Jan Ole Frantzen (4), Inger Riise Bergheim (5), Anne-Lise Børresen- Dale (5,6), Eiliv Lund (1) and Ruth H. Paulssen (2,3),       1Department of Community Medicine, UiT-The Arctic University of Norway, N-9037 Tromsø, Norway2Department of Clinical Medicine &amp; 3Genomics Support Center Tromsø (GSCT), UiT- The  Arctic University of Norway, N-9037 Tromsø, Norway4University Hospital of North Norway, Narvik Hospital, N-8516 Narvik, Norway  5Department of Cancer Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital HF, N-0310 Oslo, Norway    6Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway;     Aim:Gene expression analysis in tissue are established and valuable tools in breast cancer research. However, knowledge about variation in gene expression in normal breast tissue has not been widely explored. Surrogates for normal breast tissue vary between studies making comparisons between them difficult. There is a need to describe gene expression in normal breast tissue and its normal variation, establishing robust base line for further studies.Matherial and Methods:Using microarray technology, we analyzed a large (n=311), representative sample of breast biopsies from healthy postmenopausal women in the Norwegian Woman and Cancer study (NOWAC). We investigated gene expression variability following frequent exposures such as smoking, HRT and alcohol consumption in non-experimental conditions.Results:We observed that the overall gene expression level in normal breast tissue is low and not strongly influenced by exposure to HRT, alcohol or smoking. However, pathway analyses revealed enrichment of different gene sets between exposed and non-exposed groups indicating that these exposures are reflected in normal breast tissue. On the single gene level, Cytochrome P450 (CYP1B1) showed significant up-regulation with a fold-change of 1.36 and p&lt;0.05 in smokers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002077","title":"Structural_variation_following_telomere_crisis","description":"This is a whole genome sequencing analysis to identify patterns of structural variation following telomere crisis","abstract":"To approximate telomere crisis in vitro, Titia de Lange's lab generated a derivative of the hTERT ex- pressing RPE-1 retinal pigment epithelial cell line in which theRband p53 pathways were disabled with shRNAs to Rb and p21. To induce the telomere fusions typical of telomere crisis, they used a dox-inducible dominant negative allele of TRF2 (TRF2-DN), which deprotects telomeres and induces telomere fusions. This was then used to generate populations of cells that had experienced telomere crisis, which were then expanded as single-cell derived clones for genomic analysis. Here, we sequence at low coverage a large number of cells to identify those with evidence of copy number changes indicative of telomere crisis. Those with telomere crisis will then be sequenced at higher depth to identify patterns of structural variation and point mutations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002078","title":"Reconstructing the dispersals and adaptive history of Bantu-speaking populations in Africa and North America","description":"Bantu languages are spoken by ~310 million Africans, yet the genetic history of Bantu-speaking populations remains largely unexplored. We generated genomic data for 1,318 individuals from 35 populations in western central Africa, where Bantu languages originated. We found that early Bantu speakers first moved southward, through the equatorial rainforest, before spreading toward eastern and southern Africa. We also found that genetic adaptation of Bantu speakers was facilitated by admixture with autochthonous populations, particularly for the HLA and LCT loci. Finally, we identified a major contribution of western central African Bantu speakers to the ancestry of African Americans, whose genomes present no strong signals of natural selection. Together, these results highlight the contribution of Bantu-speaking peoples to the complex genetic history of Africans and African Americans.","abstract":"Bantu languages are spoken by ~310 million Africans, yet the genetic history of Bantu-speaking populations remains largely unexplored. We generated genomic data for 1,318 individuals from 35 populations in western central Africa, where Bantu languages originated. We found that early Bantu speakers first moved southward, through the equatorial rainforest, before spreading toward eastern and southern Africa. We also found that genetic adaptation of Bantu speakers was facilitated by admixture with autochthonous populations, particularly for the HLA and LCT loci. Finally, we identified a major contribution of western central African Bantu speakers to the ancestry of African Americans, whose genomes present no strong signals of natural selection. Together, these results highlight the contribution of Bantu-speaking peoples to the complex genetic history of Africans and African Americans.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-12T08:29:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002079","title":"Ancient DNA analysis of archaeological remains","description":"Illumina next generation sequencing data from two Egyptian mummies, Nakht-Ankh and Khnum-Nakht","abstract":"Illumina next generation sequencing data from two Egyptian mummies, Nakht-Ankh and Khnum-Nakht","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002080","title":"normR: Regime enrichment calling for ChIP-seq data","description":"ChIP-seq probes genome-wide localization of DNA-associated proteins. To mitigate technical biases ChIP-seq read densities are normalized to read densities obtained by a control. Our statistical framework “normR” achieves a sensitive normalization by accounting for the effect of putative protein-bound regions on the overall read statistics. Here, we demonstrate normR’s suitability in three studies: (i) calling enrichment for high (H3K4me3) and low (H3K36me3) signal-to-ratio data; (ii) identifying two previously undescribed H3K27me3 and H3K9me3 heterochromatic regimes of broad and peak enrichment; and (iii) calling differential H3K4me3 or H3K27me3-enrichment between HepG2 hepatocarcinoma cells and primary human Hepatocytes. normR is readily available on http://bioconductor.org/packages/normr","abstract":"ChIP-seq probes genome-wide localization of DNA-associated proteins. To mitigate technical biases ChIP-seq read densities are normalized to read densities obtained by a control. Our statistical framework “normR” achieves a sensitive normalization by accounting for the effect of putative protein-bound regions on the overall read statistics. Here, we demonstrate normR’s suitability in three studies: (i) calling enrichment for high (H3K4me3) and low (H3K36me3) signal-to-ratio data; (ii) identifying two previously undescribed H3K27me3 and H3K9me3 heterochromatic regimes of broad and peak enrichment; and (iii) calling differential H3K4me3 or H3K27me3-enrichment between HepG2 hepatocarcinoma cells and primary human Hepatocytes. normR is readily available on http://bioconductor.org/packages/normr","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002081","title":"Sequencing_melanoma_germlines","description":"In this project we performed targeted sequencing of around 50 candidate melanoma genes in the germline of melanoma patients and matched controls. Our aim was to identify variants that contribute to melanoma susceptibility.","abstract":"In this project we performed targeted sequencing of around 50 candidate melanoma genes in the germline of melanoma patients and matched controls. Our aim was to identify variants that contribute to melanoma susceptibility","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-13T14:58:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002082","title":"T19_Chad_xten","description":"Sequencing of 8 individuals from Chad to study the demographic history of the region","abstract":"The Chad remains little studied on the genetic level although its location and history makes it essential to understand the genetic diversity of the African continent. Here we propose to sequence 8 individuals from Chad to complement genotype data we have recently generated at Sanger.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-14T12:32:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002083","title":"T19_Yemen","description":"Sequencing of 50 individuals from Yemen to study the demographic history of the region","abstract":"The Arabian Peninsula is a key area for understanding the early expansion(s) of humans\nfrom Africa into the rest of the world and subsequent exchanges, yet its genomics has been\nrelatively little studied. We propose to sequence 50 individuals from Yemen to complement\nour other studies in this region","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-14T12:45:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002084","title":"Lebanon_LowCov_seq","description":"we propose to investigate the genomics of a Lebanese sample. we plan (1) genotyping (2.5M) of 120 Lebanese individuals, choosing this platform to allow comparison with the 1000 Genomes and African Genome Variation project populations, (2) 8x sequencing of 100 individuals to provide unbiased population-level sequence information including allele frequencies, and (3) 30x sequencing of four individuals to allow inferences such as from PSMC/MSMC to be obtained. The current form is for the low-coverage sequencing.  \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The Middle East is a key area for understanding the evolutionary history of humans, and one of the most complex. It is one of the possible centres of the expansion of modern humans outside Africa and an established source of subsequent expansions such as that during the Neolithic into Europe and possibly North Africa. It is also likely to have experienced many less-understood migrations in several directions relevant to the history of Africa, Asia and Europe. Yet the genomics of populations in this area have been little-studied. In the current project, we propose to investigate the genomics of a Lebanese sample. We chose Lebanon because its history in the last few thousand years is relatively well-understood. In addition, our previous studies on the Lebanese population suggest Lebanon could have been a refuge for the earliest indigenous populations in the region. In this project we plan to (1) genotype 120 Lebanese individuals analyzing 2.5M variants (2) 8x sequence 100 individuals and (3) 30x sequence 4 individuals.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-14T12:47:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002085","title":"Lebanon_HighCov_seq","description":"We propose to investigate the genomics of a Lebanese sample. we plan (1) genotyping (2.5M) of 120 Lebanese individuals, choosing this platform to allow comparison with the 1000 Genomes and African Genome Variation project populations, (2) 8x sequencing of 100 individuals to provide unbiased population-level sequence information including allele frequencies, and (3) 30x sequencing of four individuals to allow inferences such as from PSMC/MSMC to be obtained. The current form is for the high-coverage sequencing.     \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The Middle East is a key area for understanding the evolutionary history of humans, and one of the most complex. It is one of the possible centres of the expansion of modern humans outside Africa and an established source of subsequent expansions such as that during the Neolithic into Europe and possibly North Africa. It is also likely to have experienced many less-understood migrations in several directions relevant to the history of Africa, Asia and Europe. Yet the genomics of populations in this area have been little-studied. In the current project, we propose to investigate the genomics of a Lebanese sample. We chose Lebanon because its history in the last few thousand years is relatively well-understood. In addition, our previous studies on the Lebanese population suggest Lebanon could have been a refuge for the earliest indigenous populations in the region. In this project we plan to (1) genotype 120 Lebanese individuals analyzing 2.5M variants (2) 8x sequence 100 individuals and (3) 30x sequence 4 individuals.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-14T12:49:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002086","title":"Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis","description":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","abstract":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002087","title":"The BC Cancer Agency's Personalized Onco-Genomics Project","description":"The BC Cancer Agency's Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","abstract":"The BC Cancer Agency's Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002088","title":"2016_10_14_15_23_11_261_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002090","title":"2016_10_14_15_23_22_039_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002091","title":"A new subgroup of hepatocellular adenomas with sonic hedgehog pathway activation","description":"Hepatocellular adenomas (HCA) are benign liver tumors divided in molecular subtypes characterized by mutations inactivating HNF1A, activating β-catenin or the IL-6/JAK/STAT inflammatory pathway. Molecular analyses of 533 HCA developed in 411 patients identified a new tumor subgroup with Sonic Hedgehog pathway activation due to focal deletions creating INHBE promoter/GLI1 fusions.","abstract":"Hepatocellular adenomas (HCA) are benign liver tumors divided in molecular subtypes characterized by mutations inactivating HNF1A, activating β-catenin or the IL-6/JAK/STAT inflammatory pathway. Molecular analyses of 533 HCA developed in 411 patients identified a new tumor subgroup with Sonic Hedgehog pathway activation due to focal deletions creating INHBE promoter/GLI1 fusions.","study_type":"Other","pubmed_ids":[27939373],"external_links":null,"is_released":true,"released_date":"2016-10-14T23:20:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002092","title":"The ICGC-TCGA DREAM Somatic Mutation Calling - Tumour Heterogeneity Challenge","description":"Tumors are composed of many different cell types, ranging from the normal tissue micro-environment, infiltrating immune cells and tumour cells. This group of tumour cells is itself intrinsically highly heterogeneous, driven by the rapid mutation rate of cancer cells to become a mixture of different sub-populations. These different types of cells, called subclones, have different sets of mutations in their DNA. Because some subclones evolve from others, many subclones share mutations. While it is increasingly easy to determine what mutations are present in the tumor, it remains very difficult to determine which subclones have which mutations. The task of assigning mutations to subclones is called subclonal reconstruction.The ICGC-TCGA DREAM Somatic Mutation Calling - Tumour Heterogeneity Challenge (SMC-Het) is an international effort to improve standard methods for subclonal reconstruction: to quantify and genotype each individual cell population present within a tumor. The goal of this challenge is to identify the best subclonal reconstruction algorithms and to identify the conditions that affect their performance.","abstract":"Tumors are composed of many different cell types, ranging from the normal tissue micro-environment, infiltrating immune cells and tumour cells. This group of tumour cells is itself intrinsically highly heterogeneous, driven by the rapid mutation rate of cancer cells to become a mixture of different sub-populations. These different types of cells, called subclones, have different sets of mutations in their DNA. Because some subclones evolve from others, many subclones share mutations. While it is increasingly easy to determine what mutations are present in the tumor, it remains very difficult to determine which subclones have which mutations. The task of assigning mutations to subclones is called subclonal reconstruction.The ICGC-TCGA DREAM Somatic Mutation Calling - Tumour Heterogeneity Challenge (SMC-Het) is an international effort to improve standard methods for subclonal reconstruction: to quantify and genotype each individual cell population present within a tumor. The goal of this challenge is to identify the best subclonal reconstruction algorithms and to identify the conditions that affect their performance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-17T17:56:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002093","title":"Transcriptional and functional profiling defines human small intestinal macrophage subsets","description":"Macrophages (Mf) are instrumental in maintaining immune homeostasis in the intestine, yet studies on origin and heterogeneity of human intestinal Mf are scarce. Here, we identified four distinct Mf subpopulations in human small intestine (SI). Assessment of their turnover in duodenal transplants revealed that all Mf subsets were completely replaced over time; Mf1 and Mf2, phenotypically similar to peripheral blood monocytes (PBMo), were largely replaced within 3 weeks, whereas two subsets with features of mature Mf, Mf3 and Mf4, exhibited significantly slower replacement. Mf3 and Mf4 localized differently in SI; Mf3 formed a dense network in mucosal lamina propria, whereas Mf4 was enriched in submucosa. Transcriptomic analysis showed that all Mf subpopulations subsets were markedly distinct from PBMo and dendritic cells (DC). Compared to PBMo, Mf subpopulations showed reduced responsiveness to proinflammatory stimuli, but were proficient at endocytosis of particulate and soluble material. These data provide a comprehensive analysis of human SI Mf population and suggest a precursor-progeny relationship with PBMo.","abstract":"Macrophages (Mf) are instrumental in maintaining immune homeostasis in the intestine, yet studies on origin and heterogeneity of human intestinal Mf are scarce. Here, we identified four distinct Mf subpopulations in human small intestine (SI). Assessment of their turnover in duodenal transplants revealed that all Mf subsets were completely replaced over time; Mf1 and Mf2, phenotypically similar to peripheral blood monocytes (PBMo), were largely replaced within 3 weeks, whereas two subsets with features of mature Mf, Mf3 and Mf4, exhibited significantly slower replacement. Mf3 and Mf4 localized differently in SI; Mf3 formed a dense network in mucosal lamina propria, whereas Mf4 was enriched in submucosa. Transcriptomic analysis showed that all Mf subpopulations subsets were markedly distinct from PBMo and dendritic cells (DC). Compared to PBMo, Mf subpopulations showed reduced responsiveness to proinflammatory stimuli, but were proficient at endocytosis of particulate and soluble material. These data provide a comprehensive analysis of human SI Mf population and suggest a precursor-progeny relationship with PBMo.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-19T09:20:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002094","title":"Genomic and Epigenomic Features of Primary and Recurrent Hepatocellular Carcinomas","description":"Intratumor heterogeneity and divergent clonal lineages within and among primary and recurrent hepatocellular carcinomas (HCCs) produce challenges to patient management. We investigated genetic and epigenetic variations within liver tumors, among hepatic lesions, and between primary and relapsing tumors. We performed whole-genome, whole-exome, or targeted capture sequencing analyses HCC specimens collected from multiple tumor regions and matched initial and recurrent tumors to obtain a systematic evaluation of intra- and intertumor genetic heterogeneity in HCC samples and to identify genetic changes associated with tumor progression and recurrence.","abstract":"Intratumor heterogeneity and divergent clonal lineages within and among primary and recurrent hepatocellular carcinomas (HCCs) produce challenges to patient management. We investigated genetic and epigenetic variations within liver tumors, among hepatic lesions, and between primary and relapsing tumors. We performed whole-genome, whole-exome, or targeted capture sequencing analyses HCC specimens collected from multiple tumor regions and matched initial and recurrent tumors to obtain a systematic evaluation of intra- and intertumor genetic heterogeneity in HCC samples and to identify genetic changes associated with tumor progression and recurrence.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-19T14:09:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002095","title":"Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis","description":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","abstract":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002096","title":"The BC Cancer Agency's Personalized Onco-Genomics Project","description":"The BC Cancer Agency's Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","abstract":"The BC Cancer Agency's Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002097","title":"2016_10_20_09_49_08_888_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002099","title":"2016_10_20_09_52_26_881_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002100","title":"The Asian Diversity Project: genotyping of 37 Asian populations and ethnic groups","description":"The Asian Diversity Project (ADP) assembled 37 cosmopolitan and ethnic minority populations in Asia that have been densely genotyped across over half a million markers to study patterns of genetic diversity and positive natural selection.","abstract":"The Asian Diversity Project (ADP) assembled 37 cosmopolitan and ethnic minority populations in Asia that have been densely genotyped across over half a million markers to study patterns of genetic diversity and positive natural selection.","study_type":"Other","pubmed_ids":[28098149],"external_links":null,"is_released":true,"released_date":"2016-10-22T16:51:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002101","title":"Genome_wide_association_study_of_vaccine_responses_in_infants_living_in_the_Developing_World__VaccGene___Crypto_cohort__Bangladesh_","description":"It is estimated that up to 70% of the variability in response to some vaccines administered in childhood is inherited but the identification of the genetic factors responsible for this variation has not yet been prioritised. We have set up one of the largest genome-wide association studies of vaccine responses ever undertaken, which will provide unparalleled power to identify the genetic factors associated with the response to all of the most commonly used childhood vaccines worldwide. This dataset refers to the Crypto cohort from Bangladesh.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"It is estimated that up to 70% of the variability in response to some vaccines administered in childhood is inherited but the identification of the genetic factors responsible for this variation has not yet been prioritised. We have set up one of the largest genome-wide association studies of vaccine responses ever undertaken, which will provide unparalleled power to identify the genetic factors associated with the response to all of the most commonly used childhood vaccines worldwide. This dataset refers to the Crypto cohort from Bangladesh.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002102","title":"Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing","description":"Background \nSingle-cell micro-metastases of solid tumors often occur in the bone marrow. These disseminated tumor cells (DTCs) may resist therapy and lay dormant or progress to cause overt bone and visceral metastases. The molecular nature of DTCs remains elusive, as well as when and from where in the tumor they originate. Here, we apply single-cell sequencing to identify and trace the origin of DTCs in breast cancer. \n\nResults \nWe sequence the genomes of 63 single cells isolated from six non-metastatic breast cancer patients. By comparing the cells DNA copy number aberration (CNA) landscapes with those of the primary tumors and lymph node metastasis, we establish that 53% of the single cells morphologically classified as tumor cells are DTCs disseminating from the observed tumor. The remaining cells represent either non-aberrant ‘normal’ cells or aberrant cells of unknown origin that have CNA landscapes discordant from the tumor. Further analyses suggest that the prevalence of aberrant cells of unknown origin is age-dependent, and that at least a subset is hematopoietic in origin. Evolutionary reconstruction analysis of bulk tumor and DTC genomes enables ordering of CNA events in molecular pseudo-time and traced the origin of the DTCs to either the main tumor clone, primary tumor subclones, or subclones in an axillary lymph node metastasis. \n\nConclusions \nSingle-cell sequencing of bone marrow epithelial-like cells, in parallel with intra-tumor genetic heterogeneity profiling from bulk DNA, is a powerful approach to identify and study DTCs, yielding insight into metastatic processes. A heterogeneous population of CNA-positive cells is present in the bone marrow of non-metastatic breast cancer patients, only part of which are derived from the observed tumor lineages.","abstract":"Background \nSingle-cell micro-metastases of solid tumors often occur in the bone marrow. These disseminated tumor cells (DTCs) may resist therapy and lay dormant or progress to cause overt bone and visceral metastases. The molecular nature of DTCs remains elusive, as well as when and from where in the tumor they originate. Here, we apply single-cell sequencing to identify and trace the origin of DTCs in breast cancer. \n\nResults \nWe sequence the genomes of 63 single cells isolated from six non-metastatic breast cancer patients. By comparing the cells DNA copy number aberration (CNA) landscapes with those of the primary tumors and lymph node metastasis, we establish that 53% of the single cells morphologically classified as tumor cells are DTCs disseminating from the observed tumor. The remaining cells represent either non-aberrant ‘normal’ cells or aberrant cells of unknown origin that have CNA landscapes discordant from the tumor. Further analyses suggest that the prevalence of aberrant cells of unknown origin is age-dependent, and that at least a subset is hematopoietic in origin. Evolutionary reconstruction analysis of bulk tumor and DTC genomes enables ordering of CNA events in molecular pseudo-time and traced the origin of the DTCs to either the main tumor clone, primary tumor subclones, or subclones in an axillary lymph node metastasis. \n\nConclusions \nSingle-cell sequencing of bone marrow epithelial-like cells, in parallel with intra-tumor genetic heterogeneity profiling from bulk DNA, is a powerful approach to identify and study DTCs, yielding insight into metastatic processes. A heterogeneous population of CNA-positive cells is present in the bone marrow of non-metastatic breast cancer patients, only part of which are derived from the observed tumor lineages.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-24T18:13:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002103","title":"Whole exome sequencing of Dutch Parkinson's disease patients.","description":"As part of the International Parkinson's Disease Genomics Consortium, exomes of Parkinson's disease (PD) patients and healthy controls were sequenced to study the genetic etiology of PD. The Dutch cohort consists of 175 patients with a young age of onset below 50 years. Researchers can apply for access to fastq, vcf and binary plink files for this cohort.","abstract":"As part of the International Parkinson's Disease Genomics Consortium, exomes of Parkinson's disease (PD) patients and healthy controls were sequenced to study the genetic etiology of PD. The Dutch cohort consists of 175 patients with a young age of onset below 50 years. Researchers can apply for access to fastq, vcf and binary plink files for this cohort.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001002104","title":"Psoriatic_arthritis","description":"This is a pilot single cell mRNA sequencing experiment to study immune cells in psoriatic arthritis.","abstract":"This is a pilot single cell mRNA sequencing experiment to study immune cells in psoriatic arthritis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-25T15:54:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002105","title":"RNAseq data of polyA+ RNA from Leukocytes from 624 individuals of the SardiNIA cohort.","description":"We sequenced the polyA+ of the RNA of the leukocytes from 624 sardinian individuals with RNAseq (Illumina 2000, an average of round 60M reads per sample, 51 + 51 nt). Combining the genotype information of the same individuals (already available from the ProgeNIA project) with the transcriptome data we identified 21,183 independent expression quantitative trait loci (eQTLs) and 6,768 independent splicing quantitative trait loci (sQTLs), including 619 novel QTLs that exhibit population-specific trait associations. Using family relationships, we identified 809 segregating expression outliers and provide a new approach to study large effect regulatory variants and their relevance to traits. Our results provide insight into the effects of regulatory variants and their relationship to population history and individual genetic risk.","abstract":"We sequenced the polyA+ of the RNA of the leukocytes from 624 sardinian individuals with RNAseq (Illumina 2000, an average of round 60M reads per sample, 51 + 51 nt). Combining the genotype information of the same individuals (already available from the ProgeNIA project) with the transcriptome data we identified 21,183 independent expression quantitative trait loci (eQTLs) and 6,768 independent splicing quantitative trait loci (sQTLs), including 619 novel QTLs that exhibit population-specific trait associations. Using family relationships, we identified 809 segregating expression outliers and provide a new approach to study large effect regulatory variants and their relevance to traits. Our results provide insight into the effects of regulatory variants and their relationship to population history and individual genetic risk.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-26T11:16:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002106","title":"Detecting PKD1 variants in Polycystic Kidney Disease patients by single-molecule long-read sequencing","description":"A genetic diagnosis of autosomal dominant polycystic kidney disease (ADPKD) is challenging. However, long-read single-molecule sequencing has been shown to be a reliable alternative strategy that could overcome PKD1 complexities. Using long-read sequencing to characterize a cohort of 19 patients with ADPKD, we developed an approach that provided high sensitivity in identifying PKD1 pathogenic variants, with a diagnostic yield of 94.7%. Reliable screening of ADPKD patients in a single test without interference of PKD1 homologous sequences is now possible.","abstract":"A genetic diagnosis of autosomal dominant polycystic kidney disease (ADPKD) is challenging. However, long-read single-molecule sequencing has been shown to be a reliable alternative strategy that could overcome PKD1 complexities. Using long-read sequencing to characterize a cohort of 19 patients with ADPKD, we developed an approach that provided high sensitivity in identifying PKD1 pathogenic variants, with a diagnostic yield of 94.7%. Reliable screening of ADPKD patients in a single test without interference of PKD1 homologous sequences is now possible.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-28T11:40:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002107","title":"Melanoma_brain_metastases","description":"This is a whole exome study of brain metastases in melanoma. We are studying the genomic evolution of primary cutaneous melanoma to brain met in patients with brain-only metastatic disease. We are also looking at the genomic heterogeneity in patients with temporally, anatomically and regionally separated brian metastases.","abstract":"Adjusting for incidence, melanoma has the highest propensity to metastasise to the brain(1). Prognosis for these patients remains extremely poor with median survival of around 4 months(2) and &gt;50% of melanoma-related deaths are attributable to brain metastases(3). In addition to the dismal survival implications, recurrence in the brain may result in seizures, altered mental status, paralysis and a reduced quality of life(4).  Although new targeted therapies have proven efficacy in metastatic CNS disease(5,6,7), the benefit is significantly less compared to those with extracranial metastatic melanoma. With significant advances in the management of extracranial disease, the burden from brain metastases is expected to continue to rise. \n\nBrain metastases usually develop alongside extracranial sites, however a minority present with brain as the isolated first site of visceral disease. Interestingly this particular cohort display distinct clinicopathological features, which challenge the current paradigm of melanoma progression. In particular they harbour primaries that are thinner, have no mitoses and a greater percentage present with AJCC stage I disease relative to those with other visceral sites of disease(8). They can also often be treated with locoregional therapies including surgery or stereotactic radiosurgery and their survival is significantly better(9). \n\nTo identify molecular features predisposing to brain metastases and primary CNS disease we are undertaking genome sequencing of brain tumours from melanoma patients alongside matched primary tumour and germline DNA. We will use this powerful genomic information to study variations in single nucleotide variations as well as DNA copy number aberrations. We will look particularly at the expression of immune-related genes and for predisposing genes within the patients’ germline DNA. We will further study variations in gene and protein expression and correlate this genomic and transcriptomic information with clinicopathological phenotypes with reference to existing risk stratification tools. Finally, we will explore the functional significance of the molecular signatures using gene-editing techniques in established in-vitro and in-vivo models.  \n\nAccess to quality tumoural tissue from melanoma brain metastases is exceedingly rare and studies devoted to this particular complication are hugely lacking. We now have the funding, technology, expertise and experience to undertake detailed molecular analyses that could not have otherwise taken place. We strongly believe that this collaboration will provide an unprecedented detailed molecular insight into a common and devastating complication. These rarer subgroups may further illuminate a novel mechanism of melanoma progression that could ultimately be exploited for early diagnosis. \n\n1.\tBarnholtz-Sloan. J Clin Oncol. 2004;22(14):2865-72.\n2.\tFonkem. Expert Rev. Neurother. 2012;12:1207–15.\n3.\tDavies. Cancer. 2011 Apr 15;117(8):1687-96. \n4.\tRamakirshna. Am Soc Clin Oncol Educ Book. 2013:399-403. \n5.\tDummer. Eur J Cancer. 2014 Feb;50(3):611-21. \n6.\tLong. Lancet Oncol. 2012 Nov;13(11):1087-95. \n7.\tMargolin. Lancet Oncol. 2012 May;13(5):459-65.\n8.\tMa. Neuro-Oncology. 2012;14(7):849-858. \n9.\tRaizer. Neuro-Oncology. 2008;10(2):199-207.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-10-28T14:45:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002108","title":"De novo assembly of 150 Danish genomes reveals rich structural complexity","description":"Most known genetic variation in human genomes has been called from comparison of short reads to the reference genome, an approach biased against finding complex variation. We sequenced 150 individuals from 50 parent-offspring trios with multiple insert-size libraries to very high coverage. We show that each genome could be independently de novo assembled into a small number of high-quality scaffolds (median N50 &gt; 21 Mb), each of quality comparable to long read assemblies while being very cost-effective. We show that our variant call set from comparing de novo assemblies is far more complete in terms of complex variation than previous studies. Importantly, even the complex 4-5 Mb extended MHC region was assembled and resolved into haplotypes, revealing &gt;700kb novel sequence in this important region of the genome, and major parts of the Y chromosome including some palindromes were assembled with high accuracy. Finally, we show that our variant call-set allows for the genotyping of many more complex variants when used as a reference-panel for imputation into SNP-chip data or into previously resequenced genomes.","abstract":"Most known genetic variation in human genomes has been called from comparison of short reads to the reference genome, an approach biased against finding complex variation. We sequenced 150 individuals from 50 parent-offspring trios with multiple insert-size libraries to very high coverage. We show that each genome could be independently de novo assembled into a small number of high-quality scaffolds (median N50 &gt; 21 Mb), each of quality comparable to long read assemblies while being very cost-effective. We show that our variant call set from comparing de novo assemblies is far more complete in terms of complex variation than previous studies. Importantly, even the complex 4-5 Mb extended MHC region was assembled and resolved into haplotypes, revealing &gt;700kb novel sequence in this important region of the genome, and major parts of the Y chromosome including some palindromes were assembled with high accuracy. Finally, we show that our variant call-set allows for the genotyping of many more complex variants when used as a reference-panel for imputation into SNP-chip data or into previously resequenced genomes.","study_type":"Other","pubmed_ids":[28746312],"external_links":null,"is_released":true,"released_date":"2016-10-31T13:04:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002109","title":"CRISPR_lethality_screens_in_hypoxic_cells","description":"We will perform a genome-wide (CRISPR)-CRISPR-associated (Cas9) screen in normoxia and hypoxia in the absence and presence of one of novel hypoxia/HIF inhibitors to identify genes involved in mediating anti-tumour activities in normoxia and hypoxia with and without hypoxia/HIF inhibition.","abstract":"Hypoxia (low oxygen concentration) is a key feature of most solid tumours. Increased activation of hypoxia inducible factor (HIF) transcription factors is a key feature of most human cancers and is associated with treatment resistance and poor patient prognosis using front line treatments. HIF controls a variety of cellular responses that enables tumour cells to survive, metabolically adapt and metastasize. Harnessing hypoxia responses and preventing HIF activation in tumour cells blocks tumour progression and metastasis and improves the efficacy of several treatments used clinically.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002110","title":"North American Brain Expression Consortium (NABEC) Exome Sequencing","description":"A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation, particularly within the context of human tissues. We describe a set of integrated experiments designed to investigate the effects of common genetic variability on mRNA expression distinct human brain regions. We show that brain tissues may be readily distinguished based on expression profile. We find an abundance of genetic cis regulation mRNA expression. We observe that the largest magnitude effects occur across distinct brain regions. We believe these data, which we have made publicly available, will be useful in understanding the biological effects of genetic variation.","abstract":"A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation, particularly within the context of human tissues. We describe a set of integrated experiments designed to investigate the effects of common genetic variability on mRNA expression distinct human brain regions. We show that brain tissues may be readily distinguished based on expression profile. We find an abundance of genetic cis regulation mRNA expression. We observe that the largest magnitude effects occur across distinct brain regions. We believe these data, which we have made publicly available, will be useful in understanding the biological effects of genetic variation.","study_type":"Other","pubmed_ids":[20485568,21216877,22433082,23177596],"external_links":null,"is_released":true,"released_date":"2016-10-31T15:53:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002111","title":"Spatial genomic heterogeneity in multiple myeloma revealed by multi- region sequencing","description":"The bone-marrow (BM) containing skeletal system is the reservoir of Multiple Myeloma (MM), the malignant counterpart of antibody-secreting plasma cells. To gain insight into its spatial clonal architecture, we performed multi-region whole-exome sequencing of radiology-guided fine-needle aspirates from 51 MM patients. We found spatial genomic heterogeneity in a substantial proportion of cases including bi-allelic inactivation of tumor suppressors and mutations affecting cancer genes. The amount of heterogeneous mutations associated with the size of focal tumor lesions in whole body imaging consistent with focal outgrowth of highly advanced clones. In conclusion, our results support the regional initiation of transformation processes leading to high-risk disease as well as the pre-existence of key driver events in restricted areas. As such, our study does not only provide new insights in the underlying biology of MM progression but also has considerable implications for standard diagnostic approaches in the clinic.","abstract":"The bone-marrow (BM) containing skeletal system is the reservoir of Multiple Myeloma (MM), the malignant counterpart of antibody-secreting plasma cells. To gain insight into its spatial clonal architecture, we performed multi-region whole-exome sequencing of radiology-guided fine-needle aspirates from 51 MM patients. We found spatial genomic heterogeneity in a substantial proportion of cases including bi-allelic inactivation of tumor suppressors and mutations affecting cancer genes. The amount of heterogeneous mutations associated with the size of focal tumor lesions in whole body imaging consistent with focal outgrowth of highly advanced clones. In conclusion, our results support the regional initiation of transformation processes leading to high-risk disease as well as the pre-existence of key driver events in restricted areas. As such, our study does not only provide new insights in the underlying biology of MM progression but also has considerable implications for standard diagnostic approaches in the clinic.","study_type":"Other","pubmed_ids":[28814763],"external_links":null,"is_released":true,"released_date":"2016-11-01T16:15:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002112","title":"The Molecular Evolution of Localized Prostate Cancer","description":"Prostate cancer is a common, slow-growing tumour with a long natural life history characterized by a small number of driver mutations. To understand the evolutionary paths that lead to aggressive disease, we reconstructed the phylogenetic origins of 200 localized prostate tumours. Of these, 80% show evidence of multiple subclones, and their subclonal architecture is associated with clinico-pathological features like Gleason grade and molecular ones like ETS fusion status. Early tumour development is characterized by single nucleotide mutations, while later branching shows changes in trinucleotide mutational signatures and accumulation of copy number aberrations. Specific genes are selectively mutated either prior to or following branched evolution, including MTOR and NKX3-1 and RB1. Patients with monoclonal tumours showed superior outcomes relative to those with polyclonal tumours, and the presence of subclones confounds the accuracy of molecular prognostic assays. These data demonstrate that clinically-useful subclonal information can be derived from diagnostic biopsies, and provide a profile of prostate cancer evolution prior to its initial treatment and diagnosis.","abstract":"Prostate cancer is a common, slow-growing tumour with a long natural life history characterized by a small number of driver mutations. To understand the evolutionary paths that lead to aggressive disease, we reconstructed the phylogenetic origins of 200 localized prostate tumours. Of these, 80% show evidence of multiple subclones, and their subclonal architecture is associated with clinico-pathological features like Gleason grade and molecular ones like ETS fusion status. Early tumour development is characterized by single nucleotide mutations, while later branching shows changes in trinucleotide mutational signatures and accumulation of copy number aberrations. Specific genes are selectively mutated either prior to or following branched evolution, including MTOR and NKX3-1 and RB1. Patients with monoclonal tumours showed superior outcomes relative to those with polyclonal tumours, and the presence of subclones confounds the accuracy of molecular prognostic assays. These data demonstrate that clinically-useful subclonal information can be derived from diagnostic biopsies, and provide a profile of prostate cancer evolution prior to its initial treatment and diagnosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002113","title":"Exome sequencing of United Kingdom Brain Expression Consortium samples","description":"The United Kingdom Brain Expression Consortium studies regulation of gene expression through common and rare variation. One of the main set of samples is compound by bulk brain tissue from 10 brain regions obtained from 134 controls.","abstract":"The United Kingdom Brain Expression Consortium studies regulation of gene expression through common and rare variation. One of the main set of samples is compound by bulk brain tissue from 10 brain regions obtained from 134 controls.","study_type":"Other","pubmed_ids":[25174004],"external_links":null,"is_released":true,"released_date":"2016-11-02T09:18:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002114","title":"Patients with metastatic urothelial carcinoma","description":"Samples from three patients with urothelial carcinoma and paired lymph node metastases and distant metastases. Patient 1: Muscle invasive tumor and lymph node metastasis. Patient 2: Muscle invasive tumor, lymph node metastasis, and distant metastasis in the small intestine. Patient 3: T1b tumor, lymph node metastasis, and distant metastasis in the lung","abstract":"Samples from three patients with urothelial carcinoma and paired lymph node metastases and distant metastases. Patient 1: Muscle invasive tumor and lymph node metastasis. Patient 2: Muscle invasive tumor, lymph node metastasis, and distant metastasis in the small intestine. Patient 3: T1b tumor, lymph node metastasis, and distant metastasis in the lung","study_type":"Other","pubmed_ids":[27582092],"external_links":null,"is_released":true,"released_date":"2016-11-02T10:20:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002115","title":"MYC Drives Progression of Small Cell Lung Cancer to a Variant Neuroendocrine Subtype with Vulnerability to Aurora Kinase Inhibition","description":"Loss of the tumor suppressors RB1 and TP53 and MYC amplification are frequent oncogenic events in small cell lung cancer (SCLC). We show that Myc expression cooperates with Rb1 and Trp53 loss in the mouse lung to promote aggressive, highly metastatic tumors, that are initially sensitive to chemotherapy followed by relapse, similar to human SCLC. Importantly, MYC drives a neuroendocrine-low “variant” subset of SCLC with high NEUROD1 expression corresponding to transcriptional profiles of human SCLC. Targeted drug screening reveals that SCLC with high MYC expression is vulnerable to Aurora kinase inhibition, which combined with chemotherapy strongly suppresses tumor progression and increases survival. These data identify molecular features for patient stratification and uncover a novel targeted treatment approach for MYC-driven SCLC.","abstract":"Loss of the tumor suppressors RB1 and TP53 and MYC amplification are frequent oncogenic events in small cell lung cancer (SCLC). We show that Myc expression cooperates with Rb1 and Trp53 loss in the mouse lung to promote aggressive, highly metastatic tumors, that are initially sensitive to chemotherapy followed by relapse, similar to human SCLC. Importantly, MYC drives a neuroendocrine-low “variant” subset of SCLC with high NEUROD1 expression corresponding to transcriptional profiles of human SCLC. Targeted drug screening reveals that SCLC with high MYC expression is vulnerable to Aurora kinase inhibition, which combined with chemotherapy strongly suppresses tumor progression and increases survival. These data identify molecular features for patient stratification and uncover a novel targeted treatment approach for MYC-driven SCLC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-02T13:39:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002116","title":"TESTING","description":"TEST","abstract":"TEST","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002117","title":"Identification_of_synthetic_lethal_genes_by_CRISPR_Cas9_library","description":"Sequencing is performed on PCR products from the amplification of gRNA segments introduced into cell lines (some are commercial, some are derived by collaborators, as described in HMDMC 13/076). Cellular DNA or RNA are not sequenced. This data is defined as \"Other Biological/Biochemical Assay Data\" under the WTSI datasharing guidelines and consequently will be released at the time of publication and/or through faculty websites. \n\nSEQUENCING DETAILS: in October 2016 3 DNA samples will be submitted for PCR amplification and purification through CGP pipeline using Thompson's custom primer set and PCR settings and sequencing with Hiseq using a custom protocol (with 3 forward reads to read sgRNA1, sgRNA2 and the index, optimized with Illumina Bespoke Sanger team); read length 50bp. The following set of samples will be submitted in later 2016 and ealry 2017 as cell pellet to be processed through CGP Cas9 pipeline (Thompson's oligos and protocols) and sequences on Hiseq (same custom sequencing protocol described above)\n\nWe are utilizing a custom CRISPR/Cas9 library to identify synthetic lethal gene pairs. Cells will be transduced with LV expressing Cas9, then infected with LV expressign the library of 42'000 sgRNA pairs. Cell pellet will be collected from the cell population at different timepoints. The samples will be processed by CGP pipeline customized for the specific protocol and then sequenced to identify the 19bp of the sgRNA and quantify their representation.","abstract":"Cancer is one of the leading causes of death worldwide and the current therapies still results in a dismal prognosis. \nIn order to indetify new cancer vulnerabilities we designed and develop a new CRISPR Cas9 library that target in the same cells putative synthetic lethal gene pairs. This experimental approach will be applied to melanoma and other type of cancer cell lines in order to identify those gene pairs whose concurrent loss induce cell lethality\nThis approach can allow the identification of new cancer therapeutic target for a data drive generation of the next generation of cancer therapies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-08T15:58:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002118","title":"Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis","description":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","abstract":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002119","title":"The BC Cancer Agency's Personalized Onco-Genomics Project","description":"The BC Cancer Agency's Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","abstract":"The BC Cancer Agency's Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002120","title":"2016_11_08_16_25_21_435_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002122","title":"2016_11_08_16_25_33_083_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002123","title":"Meta-analysis of Genome-Wide-Association Sudies for plasma Factor XI","description":"Coagulation factor XI (FXI) has become increasingly interesting for its role in pathogenesis of thrombosis. We performed a genome-wide association study (GWAS) for plasma FXI levels, using novel data imputed to the 1000 Genomes reference panel. Individual GWAS analyses, including a total of 16,169 European individuals from the ARIC, GHS, MARTHA and PROCARDIS studies, were meta-analyzed, and results are presented here.","abstract":"Coagulation factor XI (FXI) has become increasingly interesting for its role in pathogenesis of thrombosis. We performed a genome-wide association study (GWAS) for plasma FXI levels, using novel data imputed to the 1000 Genomes reference panel. Individual GWAS analyses, including a total of 16,169 European individuals from the ARIC, GHS, MARTHA and PROCARDIS studies, were meta-analyzed, and results are presented here.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-09T10:20:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002124","title":"FFPE_normals_v2_gbm_wtsi_panel","description":"Targeted pulldown of approx 60 ffpe normal samples to use as normal controls","abstract":"Targeted pulldown of approx 60 ffpe normal samples to use as normal controls","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-09T10:51:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002125","title":"Identification_of_drug_resistance_genes_in_melanoma_by_CRISPR_Cas9_library_screening","description":"*Sequencing is performed on PCR products from the amplification of gRNA segments introduced into cell lines (some are commercial, some are derived by collaborators, as described in HMDMC 13/076). Cellular DNA or RNA are not sequenced. This data is defined as \"Other Biological/Biochemical Assay Data\" under the WTSI datasharing guidelines and consequently will be released at the time of publication and/or through faculty websites. \nPLEASE SEQUENCE WITH THE CUSTOM 19BP APPROACH AND OLIGOS FROM CGP PIPELINE (from Fiona Behan)\n\nWe are utilizing a genome-wide CRISPR/Cas9 library to identify genes involved in the resistance to a drug combination of interest. Cells will be transduced with LV expressing Cas9, then infected with LV expressign the library of 100'000 sgRNAs. These cells will then undergo selection with the drug combination of interest for 2-3 weeks. DNA will be collected from the cell population before and after the drug selection. DNA will be processed by CGP pipeline (2 nested PCR) and then sequenced to identify the 19bp of the sgRNA and quantify their representation.","abstract":"Melanoma causes more than one death every hour in the US and, despite promising advances, improved therapies are still required to increase patient survival. We have performed high-thoughput drug screening to identify new drug combination for the treatment of melanoma.\nWe are now applying a genome-wide CRISPR/Cas9 screening to identify those genes whose loss confer resistance to a new promising combined therapy. There results will inform on the molecular mechanism of the new therapy and prospectively might allow a better stratification of the patients.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002126","title":"CRISPR_AML_Differentiation_Targets","description":"Whole genome CRISPR knock-out screen to identify genes involved in AML differentiation.","abstract":"Mutations that block differentiation constitute the first step in the evolution towards AML, and are hence an appealing therapeutic target. Differentiating therapies have dramatically improved the prognosis of AML driven by a PML-RARA fusion gene (acute promyelocytic leukaemia, or APML). Potential targets for differentiating therapies in other molecular subclasses of AML remain unknown. In order to identify potential targets of gene targets for novel differentiating agents, we performed a genome-wide CRISPR screen in AML cell lines and identified gene knock-outs that induce differentiation by flow-sorting pooled transduced cells at multiple timepoints. We compared sgRNA enrichment in differentating  and undifferentiating cells at each time point.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002127","title":"Low_input_and_single_cell_duplex_sequencing","description":"To test the incorporation of duplex adaptor in sequencing low input and single cell samples","abstract":"To test the incorporation of duplex adaptor in sequencing low input and single cell samples","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002128","title":"Preclinical_evolution_of_haematological_malignancies_","description":"This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Leukaemia occurs due to genetic changes that typically accumulate over many years. Recent work has shown that some individuals harbour leukaemia-associated gene mutations in some of their blood cells, and are at higher risk of developing blood cancers. The presence of leukaemia-associated mutations in the blood of healthy people is called ‘clonal haemopoiesis of indeterminate significance’, or CHIP. This study will investigate the natural history of CHIP over time and risk factors for progression to malignancy.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-09T12:25:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002129","title":"Molecular_Analysis_of_Breast_Carcinoma","description":"Early clonal dynamics of BRCA-1 breast cancer","abstract":"BRCA-1 is a tumour suppressor gene frequently mutated in familial breast and ovarian cancers, which play an important role in homologous recombination of DNA. Breast tissue samples were obtained from patient undergoing prophylactic mastectomy for BRCA-1 gene as well as aged-matched patient undergoing breast reduction surgery. Multiple breast organoids were obtained from breast epithelial and were clonally expanded in vitro in order to obtain enough DNA for sequencing. By doing so, we are hoping to be able to detect rare clonal fraction that is critical at the very early stage of tumourigenesis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002130","title":"Method_development_for_xten_sequencing_low_input_DNA_and_single_cells","description":"To look at the artefect on single cell and low input sequencing and their effect on mutational calling","abstract":"To look at the artefect on single cell and low input sequencing and their effect on mutational calling","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002131","title":"Genomel_Melanoma_Families","description":"Around 10% of patients who present in melanoma clinics have a first degree relative with a previous diagnosis of melanoma. While around 3% have three or more relatives who have been diagnosed with the disease. In this project we will whole genome sequence patients from familial melanoma pedigrees to identify mutations in genes that drive melanomagenesis. The identification of these genes will facilitate the management of familial melanoma patients and their families.","abstract":"Around 10% of patients who present in melanoma clinics have a first degree relative with a previous diagnosis of melanoma. While around 3% have three or more relatives who have been diagnosed with the disease. In this project we will whole genome sequence patients from familial melanoma pedigrees to identify mutations in genes that drive melanomagenesis. The identification of these genes will facilitate the management of familial melanoma patients and their families.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002132","title":"The_Causes_of_Clonal_Blood_Cell_Disorders_Study___SCOR","description":"We will take a bone marrow aspirate and peripheral blood samples from a healthy patient aged around 60, and use flow cytometry to isolate 100 HSCs, 50 MEPs, and 50 GMPs. We will grow these up into colonies, then whole genome sequence each colony. Somatic mutations will act as a unique barcode for each clone. We will then design a panel for targeted resequencing of the mutations that we find. It will then be possible to look for these mutations in the peripheral blood over several years, to see the dynamics of how HSCs contribute to the peripheral blood in health.","abstract":"We will take a bone marrow aspirate and peripheral blood samples from a healthy patient aged around 60, and use flow cytometry to isolate 100 HSCs, 50 MEPs, and 50 GMPs. We will grow these up into colonies, then whole genome sequence each colony. Somatic mutations will act as a unique barcode for each clone. We will then design a panel for targeted resequencing of the mutations that we find. It will then be possible to look for these mutations in the peripheral blood over several years, to see the dynamics of how HSCs contribute to the peripheral blood in health.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-09T16:12:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002133","title":"Genetic_vulnerabilities_in_AML","description":"Acute myeloid leukaemia (AML) continues to have a very high mortality and its treatment has not changed for more than 20 years. Here, we propose to apply genomic-wide screens to directly identify therapeutic vulnerabilities of AML using AML cells lines with pre-defined somatic mutations. Our studies will be based on genome-wide CRISPR/CAs9 gRNA screens and will be used to identify drivers of drug resistance to standard chemotherapies.","abstract":"Acute myeloid leukaemia (AML) continues to have a very high mortality and its treatment has not changed for more than 20 years. Here, we propose to apply genomic-wide screens to directly identify therapeutic vulnerabilities of AML using AML cells lines with pre-defined somatic mutations. Our studies will be based on genome-wide CRISPR/CAs9 gRNA screens and will be used to identify drivers of drug resistance to standard chemotherapies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002134","title":"Genome_wide_CRISPR_Cas9_screening_of_Human_Cancer_Cell_Lines","description":"The study will perform genome-wide loss-of-function CRISPR-Cas9 screens across 500 genetically annotated human cancer cell lines to identify sythetic-lethal interaction between cancer genomes and targeted gene deletions.\n\n*Sequencing is performed on PCR products from the amplification of gRNA segments introduced into commercial cell lines. Cellular DNA or RNA are not sequenced. This data is defined as \"Other Biological/Biochemical Assay Data\" under the WTSI datasharing guidelines and consequently will be released at the time of publication and/or through faculty websites.","abstract":"The goal of this project is to perform genome-wide loss-of-function CRISPR-Cas9 screens across 500 genetically annotated human cancer cell lines to identify synthetic-lethal interactions between cancer genomes and targeted gene deletions.  These results will be used to identify novel drug targets whose inhibition is lethal to cancer cells with specific molecular alterations.  This project will facilliate development of CRISPR-Cas9 genome editing technologies as a target validation platform within the CTTV for use across multiple cellular models from different disease.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002135","title":"TP53_CRISPR_Vulnerabilities_in_AML","description":"Acute myeloid leukaemia (AML) continues to have a very high mortality and its treatment has not changed for more than 20 years. Here, we propose to apply genomic-wide screens to directly identify therapeutic vulnerabilities of AML using AML cells lines with pre-defined somatic mutations. Our studies will be based on genome-wide CRISPR/CAs9 gRNA screens and will be used to identify drivers of drug resistance to standard chemotherapies.","abstract":"Acute myeloid leukaemia (AML) continues to have a very high mortality and its treatment has not changed for more than 20 years. Here, we propose to apply genomic-wide screens to directly identify therapeutic vulnerabilities of AML using AML cells lines with pre-defined somatic mutations. Our studies will be based on genome-wide CRISPR/CAs9 gRNA screens and will be used to identify drivers of drug resistance to standard chemotherapies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002136","title":"Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis","description":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","abstract":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002137","title":"The BC Cancer Agency's Personalized Onco-Genomics Project","description":"The BC Cancer Agency's Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","abstract":"The BC Cancer Agency's Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002138","title":"2016_11_10_15_51_10_765_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002140","title":"2016_11_10_15_51_23_593_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002141","title":"Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis","description":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","abstract":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002142","title":"The BC Cancer Agency's Personalized Onco-Genomics Project","description":"The BC Cancer Agency's Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","abstract":"The BC Cancer Agency's Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002143","title":"2016_11_10_15_53_14_530_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002145","title":"2016_11_10_15_53_26_774_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002146","title":"Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis","description":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","abstract":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002147","title":"Genome-wide association study of prognosis in Crohn's disease","description":"Genome-wide association study of prognosis in Crohn's disease","abstract":"Genome-wide association study of prognosis in Crohn's disease","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-11T12:23:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002148","title":"Pros_WES","description":"SNUH_prospective_AML","abstract":"SNUH_prospective_AML","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002149","title":"RNA-sequencing of six Pilocytic astrocytoma tumors","description":"Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. A recurrent feature of PA is deregulation of the mitogen activated protein kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E). These features may serve as diagnostic and prognostic markers, and also facilitate development of targeted therapy. The aim of this study was to characterize the genetic alterations underlying the development of PA tumor in six cases, and evaluate methods for fusion oncogene detection. Using a combined analysis of RNA sequencing and copy number variation data we identified a new BRAF fusion involving the 5’ gene fusion partner GTF2I (7q11.23), not previously described in PA. The novel GTF2I-BRAF 19-10 fusion was found in one case, while the other five cases harbored the frequent KIAA1549-BRAF 16-9 fusion gene. Comparing fusion detection methods, Fluorescence in situ hybridization with BRAF break apart probe was the most sensitive method for detection of the two different BRAF rearrangements (GTF2I-BRAF and KIAA1549-BRAF). Our finding of a novel BRAF fusion in PA further emphasis the important role of B-Raf in tumorigenesis of these tumor types. Also, the growing list of BRAF/RAF gene fusions suggests these to be informative tumor markers in molecular diagnostics, which could guide future treatment strategies.","abstract":"Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. A recurrent feature of PA is deregulation of the mitogen activated protein kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E). These features may serve as diagnostic and prognostic markers, and also facilitate development of targeted therapy. The aim of this study was to characterize the genetic alterations underlying the development of PA tumor in six cases, and evaluate methods for fusion oncogene detection. Using a combined analysis of RNA sequencing and copy number variation data we identified a new BRAF fusion involving the 5’ gene fusion partner GTF2I (7q11.23), not previously described in PA. The novel GTF2I-BRAF 19-10 fusion was found in one case, while the other five cases harbored the frequent KIAA1549-BRAF 16-9 fusion gene. Comparing fusion detection methods, Fluorescence in situ hybridization with BRAF break apart probe was the most sensitive method for detection of the two different BRAF rearrangements (GTF2I-BRAF and KIAA1549-BRAF). Our finding of a novel BRAF fusion in PA further emphasis the important role of B-Raf in tumorigenesis of these tumor types. Also, the growing list of BRAF/RAF gene fusions suggests these to be informative tumor markers in molecular diagnostics, which could guide future treatment strategies.","study_type":"Other","pubmed_ids":[28448514],"external_links":null,"is_released":true,"released_date":"2016-11-14T15:50:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002150","title":"Inter and intra - tumor heterogeneity in Colorectal Cancer","description":"We used high depth massive parallel sequencing analyses to study 27 CRC (colorectal cancer) patients, with a total of 97 tumors (both primary and matched metastases) in addition to healthy control samples. We found inter-tumor concordance for coding mutations; in contrast, gene copy numbers were found to be highly discordant between primary tumors and metastases as validated by fluorescent in-situ hybridization. in a further step, we dissected a single tumor into 68 spatially defined samples and sequenced them separately. Here we identify evenly distributed coding mutations in APC and TP53 in all tumor areas, yet highly variable gene copy numbers in numerous genes.","abstract":"We used high depth massive parallel sequencing analyses to study 27 CRC (colorectal cancer) patients, with a total of 97 tumors (both primary and matched metastases) in addition to healthy control samples. We found inter-tumor concordance for coding mutations; in contrast, gene copy numbers were found to be highly discordant between primary tumors and metastases as validated by fluorescent in-situ hybridization. in a further step, we dissected a single tumor into 68 spatially defined samples and sequenced them separately. Here we identify evenly distributed coding mutations in APC and TP53 in all tumor areas, yet highly variable gene copy numbers in numerous genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-15T10:42:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002151","title":"Test_Policy_Accessioning","description":"testing policy accessioning service","abstract":"it had better work","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002152","title":"Deprecated 16.11.16Can be re-used for further submissions.","description":"Deprecated 16.11.16 Can be re-used for further submissions.","abstract":"Deprecated 16.11.16 Can be re-used for further submissions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002153","title":"The subclonal architecture of metastatic breast cancer: Results from a prospective community-based rapid autopsy program 'CASCADE'","description":"Background: Understanding the cancer genome is seen as a key step in improving outcomes for cancer patients. Genomic assays are emerging as a possible avenue to personalised medicine in breast cancer. The majority of work in this area has targeted primary tumours however, and very few studies have performed comprehensive profiling of advanced disease. Evolution of the cancer genome during the natural history of breast cancer is largely unknown, as is the profile of disease at death. We sought to study in detail these aspects of advanced breast cancers that have resulted in lethal disease. Methods and Findings: Three patients with ER-positive, HER2-negative breast cancer and one patient with triple negative breast cancer underwent rapid autopsy as part of an institutional prospective community-based rapid autopsy program. Cases represented a range of management problems in breast cancer, including late relapse after early stage disease; de novo metastatic disease; discordant disease response and disease refractory to treatment. Between 5 and 12 metastatic sites were collected at autopsy together with available primary tumours and longitudinal metastatic biopsies taken during life. Samples underwent paired tumour-normal whole exome sequencing and single nucleotide polymorphism arrays. Subclonal architectures were inferred by jointly analysing all samples from each patient. Mutations were validated using high depth amplicon sequencing.Between cases, there were significant differences in mutational burden, driver mutations, mutational processes and copy number variation. Within each case, we found dramatic heterogeneity in subclonal structure from primary to metastatic disease and between metastatic sites, such that no single lesion captured the breadth of disease. Metastatic cross seeding was found in each case and treatment drove subclonal diversification. Subclones displayed parallel evolution of treatment resistance in some cases, and apparent augmentation of key oncogenic drivers as an alternative resistance mechanism. We also observed the key role of mutational processes in subclonal evolution.Limitations of this study include the potential for bias introduced by joint analysis of formalin fixed archival specimens with fresh specimens, and the difficulties in resolving subclones with whole exome sequencing. Other alterations that could define subclones such as structural variants or epigenetic modifications were not assessed. Conclusions: This study highlights the variety of mechanisms that shape the genome of metastatic breast cancer, and the value of studying advanced disease in detail. Treatment drives significant genomic heterogeneity in breast cancers which has implications for disease monitoring and treatment selection in the personalised medicine paradigm.","abstract":"Background: Understanding the cancer genome is seen as a key step in improving outcomes for cancer patients. Genomic assays are emerging as a possible avenue to personalised medicine in breast cancer. The majority of work in this area has targeted primary tumours however, and very few studies have performed comprehensive profiling of advanced disease. Evolution of the cancer genome during the natural history of breast cancer is largely unknown, as is the profile of disease at death. We sought to study in detail these aspects of advanced breast cancers that have resulted in lethal disease. Methods and Findings: Three patients with ER-positive, HER2-negative breast cancer and one patient with triple negative breast cancer underwent rapid autopsy as part of an institutional prospective community-based rapid autopsy program. Cases represented a range of management problems in breast cancer, including late relapse after early stage disease; de novo metastatic disease; discordant disease response and disease refractory to treatment. Between 5 and 12 metastatic sites were collected at autopsy together with available primary tumours and longitudinal metastatic biopsies taken during life. Samples underwent paired tumour-normal whole exome sequencing and single nucleotide polymorphism arrays. Subclonal architectures were inferred by jointly analysing all samples from each patient. Mutations were validated using high depth amplicon sequencing.Between cases, there were significant differences in mutational burden, driver mutations, mutational processes and copy number variation. Within each case, we found dramatic heterogeneity in subclonal structure from primary to metastatic disease and between metastatic sites, such that no single lesion captured the breadth of disease. Metastatic cross seeding was found in each case and treatment drove subclonal diversification. Subclones displayed parallel evolution of treatment resistance in some cases, and apparent augmentation of key oncogenic drivers as an alternative resistance mechanism. We also observed the key role of mutational processes in subclonal evolution.Limitations of this study include the potential for bias introduced by joint analysis of formalin fixed archival specimens with fresh specimens, and the difficulties in resolving subclones with whole exome sequencing. Other alterations that could define subclones such as structural variants or epigenetic modifications were not assessed. Conclusions: This study highlights the variety of mechanisms that shape the genome of metastatic breast cancer, and the value of studying advanced disease in detail. Treatment drives significant genomic heterogeneity in breast cancers which has implications for disease monitoring and treatment selection in the personalised medicine paradigm.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-17T06:15:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002154","title":"SNU_PROSPECTIVE","description":"This study includes 5 paired samples of Korean AML paitients. 5 AML tumor samples are paired with each normal(Saliva or BM derived) sequencing data.The results of this WES study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.","abstract":"This study includes 5 paired samples of Korean AML paitients. 5 AML tumor samples are paired with each normal(Saliva or BM derived) sequencing data.The results of this WES study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-17T06:32:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002155","title":"MYO-SEQ: targeted exome sequencing of patients with limb-girdle weakness and/or high ck levels","description":"The MYO-SEQ project: application of exome sequencing technologies to 1,000 patients affected by limb-girdle weakness of unknown origin Genomic mutations are a large causative component of rare neuromuscular disorders, with exonic variations capable of altering the function of encoded proteins. Here, we apply targeted whole exome sequencing (WES) to patients with unexplained limb-girdle weakness. This approach should increase the diagnostic rates of limb-girdle muscular dystrophies, contribute to the healthcare of affected patients, and expand existing genotype-phenotype correlations. One thousand patients were recruited by clinicians throughout Europe. Inclusion criteria stipulated that patients must be &gt;10 years of age at onset, presenting with limb-girdle weakness and elevated serum creatine kinase activity. Phenotypic data was collected using PhenoTips, and WES was completed at the Broad Institute using an Illumina exome capture and a 38 Mb baited target with &gt;250 ng DNA. The variant call set was uploaded onto xBrowse and an analysis of 169 candidate genes for limb-girdle weakness was performed. The analysis of &gt;500 patient samples from 21 countries is now complete; the remaining analyses are ongoing. We have annotated causal variants in 42% of these patients, with mutations identified in 52 of the 169 candidate genes. Causal variants were most frequently identified in CAPN3 (LGMD2A), RYR1 (central core disease) and DYSF (LGMD2B). Of particular interest was the identification of a TTN founder mutation (LGMD2J) in a Serbian sub-population. Variants associated with treatable conditions, such as Pompe disease and congenital myasthenic syndromes, were detected in 15 patients. Implementing WES enabled the identification of causal variants in previously undiagnosed patients with muscle weakness, in some cases leading to the treatment of debilitating diseases. We have also expanded the understanding of genotype-phenotype correlations. Our data continues to highlight the value of WES in diagnosing rare neuromuscular diseases, and presents scope to further investigate the remaining unsolved cases.","abstract":"The MYO-SEQ project: application of exome sequencing technologies to 1,000 patients affected by limb-girdle weakness of unknown origin Genomic mutations are a large causative component of rare neuromuscular disorders, with exonic variations capable of altering the function of encoded proteins. Here, we apply targeted whole exome sequencing (WES) to patients with unexplained limb-girdle weakness. This approach should increase the diagnostic rates of limb-girdle muscular dystrophies, contribute to the healthcare of affected patients, and expand existing genotype-phenotype correlations. One thousand patients were recruited by clinicians throughout Europe. Inclusion criteria stipulated that patients must be &gt;10 years of age at onset, presenting with limb-girdle weakness and elevated serum creatine kinase activity. Phenotypic data was collected using PhenoTips, and WES was completed at the Broad Institute using an Illumina exome capture and a 38 Mb baited target with &gt;250 ng DNA. The variant call set was uploaded onto xBrowse and an analysis of 169 candidate genes for limb-girdle weakness was performed. The analysis of &gt;500 patient samples from 21 countries is now complete; the remaining analyses are ongoing. We have annotated causal variants in 42% of these patients, with mutations identified in 52 of the 169 candidate genes. Causal variants were most frequently identified in CAPN3 (LGMD2A), RYR1 (central core disease) and DYSF (LGMD2B). Of particular interest was the identification of a TTN founder mutation (LGMD2J) in a Serbian sub-population. Variants associated with treatable conditions, such as Pompe disease and congenital myasthenic syndromes, were detected in 15 patients. Implementing WES enabled the identification of causal variants in previously undiagnosed patients with muscle weakness, in some cases leading to the treatment of debilitating diseases. We have also expanded the understanding of genotype-phenotype correlations. Our data continues to highlight the value of WES in diagnosing rare neuromuscular diseases, and presents scope to further investigate the remaining unsolved cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002156","title":"Whole exome sequencing of Parkinson's disease patients from the United Kingdom","description":"As part of the International Parkinson's Disease Genomics Consortium, exomes of Parkinson's disease (PD) patients and healthy controls were sequenced to study the genetic etiology of PD. This UK cohort consists of 70 PD patients. Researchers can apply for access to fastq, vcf and binary plink files for this cohort.","abstract":"As part of the International Parkinson's Disease Genomics Consortium, exomes of Parkinson's disease (PD) patients and healthy controls were sequenced to study the genetic etiology of PD. This UK cohort consists of 70 PD patients. Researchers can apply for access to fastq, vcf and binary plink files for this cohort.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-18T13:24:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002157","title":"Resequencing_candidate_genes_for_male_spermatogenic_impairment","description":"This study aims to identify novel candidate variants from human Y-chromosomal genes DAZ, BPY2 and CDY1 by resequencing the coding regions of these genes from male patients with spermatogenic impairment.\nThe coding regions of the genes have been amplified by standard PCR, amplicon lengths range from 244 to 486 bp. A total of 61 amplicons were amplified for each of the 96 patients, totalling to approx. 25 kb per sample. Amplicons were quantified by gel electrophoresis and pooled in approx. equimolar concentrations per patient. For each of the 96 submitted samples, approx. 1 microgram of amplified DNA pool is provided in a total volume of 120 microlitres.\nThe samples need to be indexed and libraries prepared for a PE250bp Illumina MiSeq run.   \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Infertility is a major medical concern, with male causes (primarily spermatogenic impairment) identified in approximately half of these cases. The most common, and clinically routinely tested, genetic factors in spermatogenetic failure are visible sex-chromosomal karyotype anomalies and sub-microscopic Y-deletions of the azoospermia factor regions (AZFa, AZFb, AZFc), with AZFc being the most common. However, the specific functions of genes in AZFc region and their role in spermatogenic impairment remain unclear. This study has resequenced the coding regions of DAZ, CDY1 and BPY2 genes in male patients with impaired spermatogenesis.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-21T11:48:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002158","title":"A living biobank of breast cancer organoids captures disease heterogeneity","description":"Breast Cancer (BC) comprises multiple distinct subtypes that differ genetically, pathologically, and clinically. Xeno-transplantation and direct culturing of tumor tissue are increasingly used in drug development and personalized medicine strategies. Here, we describe a robust protocol for long-term culturing of human mammary epithelial organoids. Using this protocol, 101 BC organoid lines were generated, broadly recapitulating the diversity of the disease. BC organoid morphologies typically matched the histopathology, hormone receptor-, and HER2 status of the original tumor. DNA copy number variations as well as sequence changes were consistent within tumor-organoid pairs and largely retained even after extended passaging. BC organoids furthermore populated all major gene expression-based classification groups and allowed drug screens in vitro and upon xenotransplantation. This study describes a representative collection of well-characterized BC organoids available for cancer research and drug development, as well as a strategy to assess in vitro drug response in a personalized fashion.","abstract":"Breast Cancer (BC) comprises multiple distinct subtypes that differ genetically, pathologically, and clinically. Xeno-transplantation and direct culturing of tumor tissue are increasingly used in drug development and personalized medicine strategies. Here, we describe a robust protocol for long-term culturing of human mammary epithelial organoids. Using this protocol, 101 BC organoid lines were generated, broadly recapitulating the diversity of the disease. BC organoid morphologies typically matched the histopathology, hormone receptor-, and HER2 status of the original tumor. DNA copy number variations as well as sequence changes were consistent within tumor-organoid pairs and largely retained even after extended passaging. BC organoids furthermore populated all major gene expression-based classification groups and allowed drug screens in vitro and upon xenotransplantation. This study describes a representative collection of well-characterized BC organoids available for cancer research and drug development, as well as a strategy to assess in vitro drug response in a personalized fashion.","study_type":"Other","pubmed_ids":[26811335,29224780],"external_links":null,"is_released":true,"released_date":"2016-11-21T15:05:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002159","title":"Assessment of de novo copy number variations in Italian patients with schizophrenia.","description":"We investigated de novo CNVs in the whole genomic DNA of schizophrenia patients and their parents and, specifically, in putative enhancer motifs.Study participants were part of a wider multicenter study, involving an Italian cohort of schizophrenia patients recruited by members of INRP - Italian Network for Research on Psychoses.Whole genomic DNA obtained from 46 family trios of schizophrenia probands was analyzed using the Enhancer Chip, a customized array CGH developed using the Agilent SurePrint G3 8X60K format, which is able to investigate the whole genome with a 300Kb resolution, specific disease loci at a tenfold higher resolution, and that was highly enriched in probes in more than 1.250 enhancer elements selected from the Vista Enhancer Browser (PLoS One. 2012;7(12):e52264).","abstract":"We investigated de novo CNVs in the whole genomic DNA of schizophrenia patients and their parents and, specifically, in putative enhancer motifs.Study participants were part of a wider multicenter study, involving an Italian cohort of schizophrenia patients recruited by members of INRP - Italian Network for Research on Psychoses.Whole genomic DNA obtained from 46 family trios of schizophrenia probands was analyzed using the Enhancer Chip, a customized array CGH developed using the Agilent SurePrint G3 8X60K format, which is able to investigate the whole genome with a 300Kb resolution, specific disease loci at a tenfold higher resolution, and that was highly enriched in probes in more than 1.250 enhancer elements selected from the Vista Enhancer Browser (PLoS One. 2012;7(12):e52264).","study_type":"Other","pubmed_ids":[29069978],"external_links":null,"is_released":true,"released_date":"2016-11-21T18:18:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002160","title":"Molecular_analysis_of_cell_confluence_in_keratinocytes","description":"Human keratinocytes display two distinct proliferation modes in vitro. The mechanism behind each of the modes is yet to be understood but through these simple cell dynamics an entire epithelial sheet can be generated from a single cell. In this stydy, we aim to identify differentially expressed genes which are associated with the switch between the two observed proliferation modes.","abstract":"We have shown that two types of colonies form in vitro. Cells in ‘balanced’ colonies divide giving rise to equal numbers of dividing and differentiating cells, leading to tissue homeostasis. Cells within ‘expanding’ colonies divide in an exponential manner, with the majority of cell divisions resulting in the generation of two proliferative cells.  Interestingly a week post-seeding cells in the middle third of expanding colonies ‘switch’ their behaviour towards a ‘balanced’ mode of division. We set up Neonatal Foreskin Keratinocyte (NFSK) cultures and allowed them to grow for up to 8 days post seeding. RNA was collected at different timepoints. Early on, the 'expanding' type of colonies should prefominate up until they switch towards the 'balanced' mode. Through the preliminary qPCR analysis, we have confirmed that the switch between the 'expanding' and 'balanced' modes should happen around day 7 post seeding. Here, we submit 3 pairs of samples collected at day 5 and 7, which should allow us to identify differentially expressed genes between the two proliferation types.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002161","title":"Methylation of Ewing sarcoma tumors (ICGC)","description":"Ewing sarcoma (ES) is a primary bone tumor initiated by an EWSR1-ETS gene fusion. To characterize the methylation of Ewing sarcoma, reduced representation bisulfite sequencing was performed.","abstract":"Ewing sarcoma (ES) is a primary bone tumor initiated by an EWSR1-ETS gene fusion. To characterize the methylation of Ewing sarcoma, reduced representation bisulfite sequencing was performed.","study_type":"Other","pubmed_ids":[28134926],"external_links":null,"is_released":true,"released_date":"2016-11-22T13:15:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002162","title":"Genome-wide AFB1-induced mutational signatures in cells, mice and human tumors – implications for molecular epidemiology","description":"We determined whole-genome mutation patterns induced by AFB1 in two human cell-lines and in two mouse models of HCC. One of these carried a hepatitis B transgene, designed to model the effect of hepatitis B infection, which synergizes with aflatoxin in human HCC risk. The cell-line mutational patterns were remarkably stable across replicates. Mutational patterns in the mouse tumors were more variable across replicates, apparently reflecting activation of additional mutagenic processes during tumorigenesis. However, the overall pattern was consistently dominated by G &gt; T mutations with a preference for TGC &gt; TTC mutations, and it exhibited substantial mutation enrichment on the non-transcribed strand. We integrated these experimental results with newly generated genomic HCC data from a geographical region of known aflatoxin exposure and with additional, publicly available human HCC data. Like the experimental systems, the human HCCs showed high rates of G &gt; T mutations and strong transcriptional strand bias, providing evidence that the HCCs were direct consequences of AFB1 exposure. The experimental data supported previous in-silico analysis that proposed a connection on epidemiological grounds between aflatoxin exposure and COSMIC mutational signature 24. However, the HCCs differed slightly from the experimental systems in that the most frequent mutations were GGC &gt; GTC. This difference might have been due to exposure to other aflatoxins, to other mutagens, or the short-term, high-dose exposure in the experimental systems compared to chronic, lower-dose exposure in HCCs. This illustrates subtleties that can arise in linking experimental mutation patterns to those in tumors.","abstract":"We determined whole-genome mutation patterns induced by AFB1 in two human cell-lines and in two mouse models of HCC. One of these carried a hepatitis B transgene, designed to model the effect of hepatitis B infection, which synergizes with aflatoxin in human HCC risk. The cell-line mutational patterns were remarkably stable across replicates. Mutational patterns in the mouse tumors were more variable across replicates, apparently reflecting activation of additional mutagenic processes during tumorigenesis. However, the overall pattern was consistently dominated by G &gt; T mutations with a preference for TGC &gt; TTC mutations, and it exhibited substantial mutation enrichment on the non-transcribed strand. We integrated these experimental results with newly generated genomic HCC data from a geographical region of known aflatoxin exposure and with additional, publicly available human HCC data. Like the experimental systems, the human HCCs showed high rates of G &gt; T mutations and strong transcriptional strand bias, providing evidence that the HCCs were direct consequences of AFB1 exposure. The experimental data supported previous in-silico analysis that proposed a connection on epidemiological grounds between aflatoxin exposure and COSMIC mutational signature 24. However, the HCCs differed slightly from the experimental systems in that the most frequent mutations were GGC &gt; GTC. This difference might have been due to exposure to other aflatoxins, to other mutagens, or the short-term, high-dose exposure in the experimental systems compared to chronic, lower-dose exposure in HCCs. This illustrates subtleties that can arise in linking experimental mutation patterns to those in tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002163","title":"KDM5B_methlyation","description":"In the DDD project we have discovered a gene, KDM5B, that is significantly enriched for both de novo loss-of-function (LoF), de novo missense and biallelic LoF mutations in the DDD 8K, and de novo LoF mutations have previously been reported in autism and intellectual disability patients. There are also patients in DDD with inherited LoFs in KDM5B, and we observe significant over-transmission. We suspect that there are modifiers of KDM5B LoFs in the patients with de novo mutations, such that it fits a “two-hit” model, or perhaps making KDM5B mutations effectively recessive.                                                                                                                                                 We wish to run two Illumina 850K/EPiC methylation chips on DDD patients with mutations in KDM5B and age-matched controls. We want to investigate whether there are changes in DNA methylation in patients with KDM5B mutations, and whether the patterns look similar between the patients carrying heterozygous (de novo or inherited) versus biallelic mutations. This is similar to an existing project on DDD probands with de novo mutations in chromatin modifying genes.                                                                                                                                                  We intend to do a bisulphite conversion on DNA extracted from whole blood (£295.20) and then run two EPiC chips of 32 samples per kit (cost £12,840.96). We would include 7 patients with de novo mutations in KDM5B (4 LoFs + 3 missense), 4 with biallelic LoFs, 15 with inherited LoFs, 13 with inherited predicted damaging missense (CADD&gt;30), 8 with heterozygous LoFs of unknown inheritance (total 47 probands), and 15 controls who are DDD probands with diagnostic de novo mutations in ion channel genes that are not expressed in blood\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"EPIC methylation arrays run on patients with various types of variants in KDM5B, and matched controls.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002164","title":"The Genetic Landscape of BCL2 Break Negative Follicular Lymphoma","description":"Background: 15% of high and 50% of low stage FL lack the t(14;18). Nevertheless, most of these cases express BCL2 by so far unknown mechanisms. Principals/Methodology: To find molecular mechanisms, triggering FL-pathogenesis in t(14;18)-negative FL, the exonic SNV-profiles of 33 FL with and 16 FL without t(14;18) were assessed by whole exome-sequencing and external SNV-data integration. The SNV-profile of the whole exome-sequenced FL was correlated with copy number, LOH and gene-expression data. Finally, the N-glycosylation status was assessed (LympTrack assay) in a separate validation cohort. Results: SNVs in FL with and without t(14;18) affected different genes, but accumulated in similar pathways, e.g. apoptosis, epigenetic processes and cell cycle/proliferation. Mutations in genes associated with immune-response were more prominently and those associated with NFkB and N-glycosylation selectively enriched in t(14;18)-negative FL. ~50% of mutated genes showed BCL2-asociation at high confidence in FL with and without t(14;18). Moreover, among the genes mutated in t(14;18)-negative FL 555 (~1/3) were affected by copy number alterations and/or copy-neutral LOH, 125 were differently expressed between FL with and without t(14;18) (p&lt;0.01) and 62 were differentially expressed and affected by copy number alterations and/or copy-neutral LOH. N-glycosylation was strongly reduced in t(14;18)-negative FL as compared to results reported for historical FL cohorts. Conclusion: These results suggest a stronger crosstalk with the microenvironment that may compensate for the lack of N-glycosylation and a diverse portfolio of SNVs that may contribute to the upregulation of BCL2 and FL pathogenesis in t(14;18)-negative FL.","abstract":"Background: 15% of high and 50% of low stage FL lack the t(14;18). Nevertheless, most of these cases express BCL2 by so far unknown mechanisms. Principals/Methodology: To find molecular mechanisms, triggering FL-pathogenesis in t(14;18)-negative FL, the exonic SNV-profiles of 33 FL with and 16 FL without t(14;18) were assessed by whole exome-sequencing and external SNV-data integration. The SNV-profile of the whole exome-sequenced FL was correlated with copy number, LOH and gene-expression data. Finally, the N-glycosylation status was assessed (LympTrack assay) in a separate validation cohort. Results: SNVs in FL with and without t(14;18) affected different genes, but accumulated in similar pathways, e.g. apoptosis, epigenetic processes and cell cycle/proliferation. Mutations in genes associated with immune-response were more prominently and those associated with NFkB and N-glycosylation selectively enriched in t(14;18)-negative FL. ~50% of mutated genes showed BCL2-asociation at high confidence in FL with and without t(14;18). Moreover, among the genes mutated in t(14;18)-negative FL 555 (~1/3) were affected by copy number alterations and/or copy-neutral LOH, 125 were differently expressed between FL with and without t(14;18) (p&lt;0.01) and 62 were differentially expressed and affected by copy number alterations and/or copy-neutral LOH. N-glycosylation was strongly reduced in t(14;18)-negative FL as compared to results reported for historical FL cohorts. Conclusion: These results suggest a stronger crosstalk with the microenvironment that may compensate for the lack of N-glycosylation and a diverse portfolio of SNVs that may contribute to the upregulation of BCL2 and FL pathogenesis in t(14;18)-negative FL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-25T10:34:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002165","title":"Somatic_mutation_in_skin_epidermis__SMS_","description":"We aim to assess the range and depth of mutations in genes linked with cancer in skin epidermis surrounding lesions which are undergoing surgical removal.  Patient history will be collected to provide a detailed outline of tumour type (including histology), skin type, and sunlight exposure.  We will perform ultra-deep targeted sequencing using genes implicated in cancer to try and understand the background of mutations surrounding these lesions","abstract":"We aim to assess the range and depth of mutations in genes linked with cancer in skin epidermis surrounding lesions which are undergoing surgical removal.  Patient history will be collected to provide a detailed outline of tumour type (including histology), skin type, and sunlight exposure.  We will perform ultra-deep targeted sequencing using genes implicated in cancer to try and understand the background of mutations surrounding these lesions","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-25T11:59:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002166","title":"Identification_of_functional_mutations_affecting_drug_resistance_by_CRISPR_Cas9","description":"By CRISPR/Cas9 we induced the KO of 4 different loci of interest in the target cell line. These 4 loci were amplified by PCR adding the  adapter PE1.0 and iPCR adapter and indexes, at the 5' and 3' of the amplicons, repsectively. The low complexity of the library requires the addition of  PhiX spike in at 30%. We need to get 500'000 150bp PE reads from the samples C025_A_C-, C025_B_C-, C025_C_C-, C084_A_C-, C084_B_C-, C084_C_C-, C025_A_nut, C025_B_nut, C025_C_nut, C084_A_nut, C084_B_nut, C084_C_nut; while we need to get 150'000 reads from the samples Molm_13_DN_1, Molm_13_CD15-_1, Molm_13_CD133-_1, Molm_13_DN_2, Molm_13_CD15-_2, Molm_13_CD133-_2, melanocytes. In order to obtain the differential coverage we require to pool different quantity of the samples. PCRs with the adapter and indexes will be provided for bead purification, Bioanalyser quality and quantity check, and pooling for sequencing","abstract":"Cancer is one of the leading causes of death worldwide and the current therapies still results in a dismal prognosis. \nWe have previously performed high throughput drug screening and combined the drug sensitivity with the genomics data available from our cell lines. We have identified candidate mutations that are associated with drug sensitivity/resistance. By CRISPR/Cas9 technology we are editing wild type and mutant cell lines for the genes of interest and we are applying drug selection to validate which mutation have a functional effect on the drug sensitivity.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002167","title":"Osteosarcoma_X10","description":"This is a continuation of the osteosarcoma work we have undertaken.","abstract":"This is a continuation of the osteosarcoma work we have undertaken.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-25T14:26:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002168","title":"Longitudinal analysis of treatment induced genomic alterations in gliomas","description":"Here, we report the longitudinal whole exome sequencing analysis  of a patient with a primary GBM and two recurrences, demonstrating the heterogeneity caused by the therapy induced molecular changes and their implications for clinical decision-making. This analysis revealed the impact of temporal evolution for tumors under the pressure of treatment. We presented that while targeted treatments eliminated some sensitive clones, there were clones that were enriched leading to resistance. This study demonstrates the importance of longitudinal genomic profiling to adjust to the dynamic nature of therapy induced molecular changes to improve the outcomes of precision therapies.","abstract":"Here, we report the longitudinal whole exome sequencing analysis  of a patient with a primary GBM and two recurrences, demonstrating the heterogeneity caused by the therapy induced molecular changes and their implications for clinical decision-making. This analysis revealed the impact of temporal evolution for tumors under the pressure of treatment. We presented that while targeted treatments eliminated some sensitive clones, there were clones that were enriched leading to resistance. This study demonstrates the importance of longitudinal genomic profiling to adjust to the dynamic nature of therapy induced molecular changes to improve the outcomes of precision therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-26T02:45:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002169","title":"MeDALL epigenetics study","description":"MeDALL- (Mechanisms of the Development of ALLergy) is a collaborative project supported by the European Union under the Health Cooperation Work Programme of the 7th Framework programme (grant agreement number 261357).MeDALL epigenetics study includes illumina 450k methylation measurements from 4 cohorts: Infancia y Medio Ambiente (INMA), Etudes des Déterminants pré et postnatals précoces du développement et de la santé de l’ENfant (EDEN), Children’s Allergy Environment Stockholm Epidemiology study(BAMSE), and Prevention and Incidence of Asthma and Mite Allergy (PIAMA)","abstract":"MeDALL- (Mechanisms of the Development of ALLergy) is a collaborative project supported by the European Union under the Health Cooperation Work Programme of the 7th Framework programme (grant agreement number 261357).MeDALL epigenetics study includes illumina 450k methylation measurements from 4 cohorts: Infancia y Medio Ambiente (INMA), Etudes des Déterminants pré et postnatals précoces du développement et de la santé de l’ENfant (EDEN), Children’s Allergy Environment Stockholm Epidemiology study(BAMSE), and Prevention and Incidence of Asthma and Mite Allergy (PIAMA)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-28T13:36:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002170","title":"Scalable whole-genome single-cell library preparation without pre-amplification","description":"Single-cell genomics is critical for understanding cellular heterogeneity in cancer, but existing library preparation methods are expensive, require sample preamplification and introduce coverage bias. Here we describe direct library preparation (DLP), a robust, scalable, and high-fidelity method that uses nanoliter-volume transposition reactions for single-cell whole-genome library preparation without preamplification. We examined 782 cells from cell lines and triple-negative breast xenograft tumors. Low-depth sequencing, compared with existing methods, revealed greater coverage uniformity and more reliable detection of copy-number alterations. Using phylogenetic analysis, we found minor xenograft subpopulations that were undetectable by bulk sequencing, as well as dynamic clonal expansion and diversification between passages. Merging single-cell genomes in silico, we generated \"bulk-equivalent\" genomes with high depth and uniform coverage. Thus, low-depth sequencing of DLP libraries may provide an attractive replacement for conventional bulk sequencing methods, permitting analysis of copy number at the cell level and of other genomic variants at the population level.","abstract":"Single-cell genomics is critical for understanding cellular heterogeneity in cancer, but existing library preparation methods are expensive, require sample preamplification and introduce coverage bias. Here we describe direct library preparation (DLP), a robust, scalable, and high-fidelity method that uses nanoliter-volume transposition reactions for single-cell whole-genome library preparation without preamplification. We examined 782 cells from cell lines and triple-negative breast xenograft tumors. Low-depth sequencing, compared with existing methods, revealed greater coverage uniformity and more reliable detection of copy-number alterations. Using phylogenetic analysis, we found minor xenograft subpopulations that were undetectable by bulk sequencing, as well as dynamic clonal expansion and diversification between passages. Merging single-cell genomes in silico, we generated \"bulk-equivalent\" genomes with high depth and uniform coverage. Thus, low-depth sequencing of DLP libraries may provide an attractive replacement for conventional bulk sequencing methods, permitting analysis of copy number at the cell level and of other genomic variants at the population level.","study_type":"Other","pubmed_ids":[28068316],"external_links":null,"is_released":true,"released_date":"2016-11-28T21:31:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002171","title":"Orphan_Tumour_Study___familial_neuroblastoma","description":"The aim of this study is to study the genomes of ultra rare childhood tumours","abstract":"The aim of this study is to study the genomes of ultra rare childhood tumours","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-11-29T11:16:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002172","title":"Whole-genome analysis of non-coding regulatory mutations in T-cell acute lymphoblastic leukemia","description":"Through integrated whole-genome and transcriptome sequencing, we performed a comprehensive and unbiased screen of non-coding driver mutations in T-cell acute lymphoblastic leukemia (T-ALL). TAL1, LMO1, and LMO2 emerged as loci with the most significant enrichment of recurrent non-coding mutations. Our genome-wide study identified novel non-coding driver mutations in T-ALL, expanding the understanding of how genomic alterations in regulatory DNA contribute to cancer pathogenesis in general.","abstract":"Through integrated whole-genome and transcriptome sequencing, we performed a comprehensive and unbiased screen of non-coding driver mutations in T-cell acute lymphoblastic leukemia (T-ALL). TAL1, LMO1, and LMO2 emerged as loci with the most significant enrichment of recurrent non-coding mutations. Our genome-wide study identified novel non-coding driver mutations in T-ALL, expanding the understanding of how genomic alterations in regulatory DNA contribute to cancer pathogenesis in general.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002173","title":"Prebiotic inulin-type fructans induce specific changes in the human gut microbiota","description":"ObjectiveContrary to the long-standing prerequisite of inducing selective (i.e. bifidogenic) effects, recent findings suggest that prebiotic interventions lead to ecosystem-wide microbiota shifts. Yet, a comprehensive characterization of this process is still lacking. Here, we apply 16S rDNA microbiota profiling and matching (GC-MS) metabolomics to assess the consequences of inulin fermentation both on the composition of the colon bacterial ecosystem and fecal metabolites profiles.DesignFecal samples collected during a double blind, randomized, cross-over intervention study (NCT02548247) set up to assess the effect of inulin consumption on stool frequency in healthy adults with mild constipation were analyzed. Fecal microbiota composition and metabolite profiles were linked to the study’s clinical outcome as well as to quality-of-life measurements recorded.ResultsWhile fecal metabolite profiles were not significantly altered by inulin consumption, our analyses did detect a modest effect on global microbiota composition. At the same time, specific inulin-induced changes in relative abundances of Anaerostipes, Bilophila, and Bifidobacterium were identified. The observed decrease in Bilophila abundances following inulin consumption was associated with both softer stools and a favorable change in constipation-specific quality of life measures.ConclusionsEcosystem-wide analysis of the effect of a dietary intervention with prebiotic inulin-type fructans on the colon microbiota revealed that this effect is specifically associated to three genera, one of which (Bilophila) representing a promising novel target for mechanistic research.","abstract":"ObjectiveContrary to the long-standing prerequisite of inducing selective (i.e. bifidogenic) effects, recent findings suggest that prebiotic interventions lead to ecosystem-wide microbiota shifts. Yet, a comprehensive characterization of this process is still lacking. Here, we apply 16S rDNA microbiota profiling and matching (GC-MS) metabolomics to assess the consequences of inulin fermentation both on the composition of the colon bacterial ecosystem and fecal metabolites profiles.DesignFecal samples collected during a double blind, randomized, cross-over intervention study (NCT02548247) set up to assess the effect of inulin consumption on stool frequency in healthy adults with mild constipation were analyzed. Fecal microbiota composition and metabolite profiles were linked to the study’s clinical outcome as well as to quality-of-life measurements recorded.ResultsWhile fecal metabolite profiles were not significantly altered by inulin consumption, our analyses did detect a modest effect on global microbiota composition. At the same time, specific inulin-induced changes in relative abundances of Anaerostipes, Bilophila, and Bifidobacterium were identified. The observed decrease in Bilophila abundances following inulin consumption was associated with both softer stools and a favorable change in constipation-specific quality of life measures.ConclusionsEcosystem-wide analysis of the effect of a dietary intervention with prebiotic inulin-type fructans on the colon microbiota revealed that this effect is specifically associated to three genera, one of which (Bilophila) representing a promising novel target for mechanistic research.","study_type":"Other","pubmed_ids":[27492975],"external_links":null,"is_released":true,"released_date":"2016-12-01T10:48:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002174","title":"The molecular landscape of colorectal cancer （17 cases）","description":"We performed whole-exome sequencing of tumor samples and adjacent normal mucosae from 17 cases to characterize the genetic alterations in china.","abstract":"We performed whole-exome sequencing of tumor samples and adjacent normal mucosae from 17 cases to characterize the genetic alterations in china.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-12-02T07:46:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002175","title":"Genomic and transcriptomic profiling of signalling networks in follicular lymphoma","description":"This dataset is composed of sequencing data from 16 patients diagnosed with follicular lymphoma, who developed transformed disease and for whom representative frozen tumor biopsy samples were available. For 14 patients there is paired material from both disease stages. DNA and RNA libraries were constructed and captured with a kinome bait library (Agilent Technologies), before sequencing on an Illumina platform.","abstract":"This dataset is composed of sequencing data from 16 patients diagnosed with follicular lymphoma, who developed transformed disease and for whom representative frozen tumor biopsy samples were available. For 14 patients there is paired material from both disease stages. DNA and RNA libraries were constructed and captured with a kinome bait library (Agilent Technologies), before sequencing on an Illumina platform.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-12-04T23:45:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002176","title":"The aim of this project is to identify, on 15 French Caucasian and 10 African-Caribbean men, through an integrative approach of DNA sequencing and transciptomic analyses, relevant genomic events that characterize or allow targeting the various phenotypes of aggressiveness of early stages of prostate cancer.","description":"Every year about 70,000 new cases of prostate cancer are diagnosed in France and 8,700 men died from this disease. But the incidence and the rate of mortality per 100,000 men in the French West Indies are respectively 1.5x and 2x upper than the rates observed in the metropolitan France. The aim of this project is to identify, on 15 French Caucasian and 10 African-Caribbean men, through an integrative approach of DNA sequencing and transciptomic analyses, relevant genomic events that characterize or allow targeting the various phenotypes of aggressiveness of early stages of prostate cancer.","abstract":"Every year about 70,000 new cases of prostate cancer are diagnosed in France and 8,700 men died from this disease. But the incidence and the rate of mortality per 100,000 men in the French West Indies are respectively 1.5x and 2x upper than the rates observed in the metropolitan France. The aim of this project is to identify, on 15 French Caucasian and 10 African-Caribbean men, through an integrative approach of DNA sequencing and transciptomic analyses, relevant genomic events that characterize or allow targeting the various phenotypes of aggressiveness of early stages of prostate cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-12-05T10:19:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002177","title":"Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis","description":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","abstract":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002178","title":"The BC Cancer Agency's Personalized Onco-Genomics Project","description":"The BC Cancer Agency's Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","abstract":"The BC Cancer Agency's Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002179","title":"2016_12_06_14_56_23_853_EBI, submitted by EBI","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002181","title":"2016_12_06_14_56_40_390_EBI, submitted by TEST","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002182","title":"Genetic Basis of Hepatosplenic T Cell Lymphoma (HSTL)","description":"Hepatosplenic T cell lymphoma (HSTL) is a rare and lethal lymphoma; the genetic drivers of this disease are unknown.  Through whole exome sequencing of 68 HSTLs, we define recurrently mutated driver genes and copy number alterations in the disease. Chromatin modifying genes including SETD2, INO80 and ARID1B were commonly mutated in HSTL, affecting 62% of cases. HSTLs manifest frequent mutations in STAT5B (31%), STAT3 (9%), and PIK3CD (9%) for which there currently exist potential targeted therapies. In addition, we noted less frequent events in EZH2, KRAS and TP53. SETD2 was the most frequently silenced gene in HSTL. We experimentally demonstrated that SETD2 acts as a tumor suppressor gene. In addition, we found that mutations in STAT5B and PIK3CD activate critical signaling pathways important to cell survival in HSTL. Our work thus defines the genetic landscape of HSTL and implicates novel gene mutations linked to HSTL pathogenesis and potential treatment targets.","abstract":"Hepatosplenic T cell lymphoma (HSTL) is a rare and lethal lymphoma; the genetic drivers of this disease are unknown.  Through whole exome sequencing of 68 HSTLs, we define recurrently mutated driver genes and copy number alterations in the disease. Chromatin modifying genes including SETD2, INO80 and ARID1B were commonly mutated in HSTL, affecting 62% of cases. HSTLs manifest frequent mutations in STAT5B (31%), STAT3 (9%), and PIK3CD (9%) for which there currently exist potential targeted therapies. In addition, we noted less frequent events in EZH2, KRAS and TP53. SETD2 was the most frequently silenced gene in HSTL. We experimentally demonstrated that SETD2 acts as a tumor suppressor gene. In addition, we found that mutations in STAT5B and PIK3CD activate critical signaling pathways important to cell survival in HSTL. Our work thus defines the genetic landscape of HSTL and implicates novel gene mutations linked to HSTL pathogenesis and potential treatment targets.","study_type":"Other","pubmed_ids":[28122867],"external_links":null,"is_released":true,"released_date":"2016-12-06T22:13:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002183","title":"Pediatric Non-Down Syndrome Acute Megakaryoblastic Leukemia is Characterized by Distinct Genomic Subsets with Varying Outcomes","description":"Acute Megakaryoblastic Leukemia (AMKL) is a subtype of acute myeloid leukemia (AML) in which cells morphologically resemble abnormal megakaryoblasts.  While extremely rare in adults, AMKL accounts for 4-15% of newly diagnosed childhood AML1-3.  A significant proportion of pediatric AMKL cases occur in children with Down syndrome (DS).  These patients have excellent outcomes and are characterized at the genomic level by a founding GATA1 mutation4-6.  In contrast, AMKL in patients without DS (non-DS-AMKL) is frequently associated with poor outcomes.  Previous efforts have identified chimeric oncogenes in a significant number of cases, including RBM15-MKL1, CBFA2T3-GLIS2, KMT2A gene rearrangements and NUP98-KDM5A7-9.  The etiology of 30-40% of cases, however, remains unknown.  To better understand the genomic landscape of non-DS-AMKL, we performed RNA and exome sequencing on specimens from 99 patients (75 pediatric and 24 adult).  We demonstrate that pediatric non-DS-AMKL is a heterogeneous malignancy that can be divided into seven subgroups with varying outcomes.  These subgroups are characterized by chimeric oncogenes with cooperating mutations in epigenetic and kinase signaling genes.  Overall, these data shed light on the etiology of AMKL and provide useful information for treatment tailoring. ","abstract":"Acute Megakaryoblastic Leukemia (AMKL) is a subtype of acute myeloid leukemia (AML) in which cells morphologically resemble abnormal megakaryoblasts.  While extremely rare in adults, AMKL accounts for 4-15% of newly diagnosed childhood AML1-3.  A significant proportion of pediatric AMKL cases occur in children with Down syndrome (DS).  These patients have excellent outcomes and are characterized at the genomic level by a founding GATA1 mutation4-6.  In contrast, AMKL in patients without DS (non-DS-AMKL) is frequently associated with poor outcomes.  Previous efforts have identified chimeric oncogenes in a significant number of cases, including RBM15-MKL1, CBFA2T3-GLIS2, KMT2A gene rearrangements and NUP98-KDM5A7-9.  The etiology of 30-40% of cases, however, remains unknown.  To better understand the genomic landscape of non-DS-AMKL, we performed RNA and exome sequencing on specimens from 99 patients (75 pediatric and 24 adult).  We demonstrate that pediatric non-DS-AMKL is a heterogeneous malignancy that can be divided into seven subgroups with varying outcomes.  These subgroups are characterized by chimeric oncogenes with cooperating mutations in epigenetic and kinase signaling genes.  Overall, these data shed light on the etiology of AMKL and provide useful information for treatment tailoring. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-12-08T14:52:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002184","title":"miR-200-regulated CXCL12β promotes fibroblast heterogeneity and immunosuppression in ovarian cancers","description":"High-grade serous epithelial ovarian cancer (HGSOC) has been recently subdivided into molecular subgroups, including the mesenchymal HGSOC associated with partial tumor-debulking surgery and poor patient survival. Consistent with stromal-related genes signatures defining mesenchymal HGSOC, we show here that stroma plays a key function in this HGSOC molecular subtype. We first highlight stromal heterogeneity in HGSOC by identifying 4 subsets of Carcinoma-Associated Fibroblast (CAF-S1-4). Mesenchymal HGSOC significantly accumulate the activated CAF-S1 subset, which exhibits immunosuppressive functions by promoting attraction, survival and activation of regulatory T-lymphocytes. The CXCL12β chemokine reliably characterizes mesenchymal HGSOC and specifically accumulates in the CAF-S1 subset through a regulation mediated by the miR-141/200a. CXCL12β promotes attraction of T-lymphocytes and is thus a key actor in CAF-S1-mediated immunosuppressive functions. In conclusion, we highlight here for the first time stromal heterogeneity and immunosuppression in mesenchymal HGSOC that could participate in the poor patient prognosis.","abstract":"High-grade serous epithelial ovarian cancer (HGSOC) has been recently subdivided into molecular subgroups, including the mesenchymal HGSOC associated with partial tumor-debulking surgery and poor patient survival. Consistent with stromal-related genes signatures defining mesenchymal HGSOC, we show here that stroma plays a key function in this HGSOC molecular subtype. We first highlight stromal heterogeneity in HGSOC by identifying 4 subsets of Carcinoma-Associated Fibroblast (CAF-S1-4). Mesenchymal HGSOC significantly accumulate the activated CAF-S1 subset, which exhibits immunosuppressive functions by promoting attraction, survival and activation of regulatory T-lymphocytes. The CXCL12β chemokine reliably characterizes mesenchymal HGSOC and specifically accumulates in the CAF-S1 subset through a regulation mediated by the miR-141/200a. CXCL12β promotes attraction of T-lymphocytes and is thus a key actor in CAF-S1-mediated immunosuppressive functions. In conclusion, we highlight here for the first time stromal heterogeneity and immunosuppression in mesenchymal HGSOC that could participate in the poor patient prognosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-12-08T16:15:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002185","title":"Single-cell profiling maps the spectrum of crosstalk between glioma cells and tumor associated macrophages","description":"Tumor associated macrophages (TAMs) are a heterogeneous glioma infiltrate, implicated in cancer progression. We performed single-cell RNA-sequencing,  to survey TAM response-patterns in glioma.","abstract":"Tumor associated macrophages (TAMs) are a heterogeneous glioma infiltrate, implicated in cancer progression. We performed single-cell RNA-sequencing,  to survey TAM response-patterns in glioma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-12-08T21:10:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002186","title":"Sequencing of pancreatic cancer primary tumors and metastases","description":"The extent of heterogeneity of driver gene mutations present in naturally occurring metastases is largely unknown, i.e. treatment-naïve metastatic disease.  To address this issue, 60x whole genome sequencing of 26 metastases from 4 patients was carried out.  We found that the identical driver gene mutations were present in every metastatic lesion of each patient studied. Passenger gene mutations not known or predicted to have functional consequences accounted for all intratumoral heterogeneity. Even with respect to these passenger gene mutations, the genetic similarity among the founding cells of metastases was markedly higher than that expected for any two cells randomly taken from a normal tissue.  The uniformity of driver gene mutations among metastases in the same patient has critical, encouraging implications for the success of future targeted therapies in advanced stage disease.","abstract":"The extent of heterogeneity of driver gene mutations present in naturally occurring metastases is largely unknown, i.e. treatment-naïve metastatic disease.  To address this issue, 60x whole genome sequencing of 26 metastases from 4 patients was carried out.  We found that the identical driver gene mutations were present in every metastatic lesion of each patient studied. Passenger gene mutations not known or predicted to have functional consequences accounted for all intratumoral heterogeneity. Even with respect to these passenger gene mutations, the genetic similarity among the founding cells of metastases was markedly higher than that expected for any two cells randomly taken from a normal tissue.  The uniformity of driver gene mutations among metastases in the same patient has critical, encouraging implications for the success of future targeted therapies in advanced stage disease.","study_type":"Other","pubmed_ids":[28092682],"external_links":null,"is_released":true,"released_date":"2016-12-09T14:34:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002187","title":"Single-cell allele specific gene expression reveals novel imprinted genes","description":"Genomic imprinting results in parental-specific gene expression. Imprinted genes are involved in the etiology of rare syndromes and have been associated with common diseases such as diabetes and cancer. Standard RNA bulk cell sequencing applied to whole tissue samples has been used to detect imprinted genes in human and mouse models. However, lowly expressed genes cannot be detected by using RNA bulk approaches. Here, we report an original and robust method that combines single-cell RNAseq and whole genome sequencing into an optimized statistical framework to analyze genomic imprinting in specific cell-types and in different individuals. Using samples from the probands of 2 family trios and 3 unrelated individuals, 1084 individual primary fibroblasts were RNA sequenced, and more than 700000 informative heterozygous single nucleotide variations (SNVs) were genotyped. The allele specific coverage per gene of each SNV in each single cell was used to fit a beta-binomial distribution to model the likelihood of a gene being expressed from one and the same allele. Genes presenting a significant aggregate allelic ratio (between 0.9-1) were retained to identify of the allelic parent of origin. Our approach allowed us to validate the imprinting status of all of the known imprinted genes expressed in fibroblasts and the discovery of 9 putative imprinted genes, thus demonstrating the advantages of single-cell over bulk RNAseq to identify imprinted genes. The proposed single-cell methodology is a powerful tool for establishing a cell type-specific map of genomic imprinting.","abstract":"Genomic imprinting results in parental-specific gene expression. Imprinted genes are involved in the etiology of rare syndromes and have been associated with common diseases such as diabetes and cancer. Standard RNA bulk cell sequencing applied to whole tissue samples has been used to detect imprinted genes in human and mouse models. However, lowly expressed genes cannot be detected by using RNA bulk approaches. Here, we report an original and robust method that combines single-cell RNAseq and whole genome sequencing into an optimized statistical framework to analyze genomic imprinting in specific cell-types and in different individuals. Using samples from the probands of 2 family trios and 3 unrelated individuals, 1084 individual primary fibroblasts were RNA sequenced, and more than 700000 informative heterozygous single nucleotide variations (SNVs) were genotyped. The allele specific coverage per gene of each SNV in each single cell was used to fit a beta-binomial distribution to model the likelihood of a gene being expressed from one and the same allele. Genes presenting a significant aggregate allelic ratio (between 0.9-1) were retained to identify of the allelic parent of origin. Our approach allowed us to validate the imprinting status of all of the known imprinted genes expressed in fibroblasts and the discovery of 9 putative imprinted genes, thus demonstrating the advantages of single-cell over bulk RNAseq to identify imprinted genes. The proposed single-cell methodology is a powerful tool for establishing a cell type-specific map of genomic imprinting.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002188","title":"The_British_Autozygosity_Populations_BioResource","description":"This data set contains whole exome sequences of individuals with self-stated parental relatedness from the East London Genes &amp; Health cohort. Rare frequency functional variants in these healthy individuals will be studied with respect to the genetic health of the participants and loss-of-function analysis of human genes.     \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This data set contains whole exome sequences of individuals with self-stated parental relatedness from the East London Genes &amp; Health cohort. Rare frequency functional variants in these healthy individuals will be studied with respect to the genetic health of the participants and loss-of-function analysis of human genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002189","title":"Gene fusion and transcriptomic landscapes of sarcomas","description":"Sarcoma represents a highly heterogeneous group of tumors. We report here the first unbiased and systematic search for gene fusions and analysis of transcriptomic profiles in 100 monomorphic sarcomas cases using RNA-sequencing profiling. Fusion genes were detected in two thirds of samples. Similarly to fusion genes such as PAX3/7-FOXO1, EWSR1/FUS-ETS, SS18-SSX, BRD3/4-NUTM1 or EWSR1/FUS/TAF15-NR4A3 characterizing well-defined entities, we show that all sarcomas displaying CIC fusions- whatever their fusion partner (being DUX4, NUTM1 or FOXO4) - form a transcriptionally homogeneous group of tumors. Likewise, tumors with either a BCOR fusion (with CCNB3, MAML3 or ZC3H7B partners) or with a BCOR internal duplication form a single biological entity. We also found that EML4-ALK fusions also characterize a homogeneous infantile fibrosarcoma subgroup. In contrast, fusions like VGLL2-NCOA2/CITED2, TMP3/TRP-NTRK1 or ETV6-NTRK3 are observed in more heterogeneous tumors. Finally, we also describe a new group of bone sarcomas characterized by EWSR1- or FUS-TFCP2 fusions.","abstract":"Sarcoma represents a highly heterogeneous group of tumors. We report here the first unbiased and systematic search for gene fusions and analysis of transcriptomic profiles in 100 monomorphic sarcomas cases using RNA-sequencing profiling. Fusion genes were detected in two thirds of samples. Similarly to fusion genes such as PAX3/7-FOXO1, EWSR1/FUS-ETS, SS18-SSX, BRD3/4-NUTM1 or EWSR1/FUS/TAF15-NR4A3 characterizing well-defined entities, we show that all sarcomas displaying CIC fusions- whatever their fusion partner (being DUX4, NUTM1 or FOXO4) - form a transcriptionally homogeneous group of tumors. Likewise, tumors with either a BCOR fusion (with CCNB3, MAML3 or ZC3H7B partners) or with a BCOR internal duplication form a single biological entity. We also found that EML4-ALK fusions also characterize a homogeneous infantile fibrosarcoma subgroup. In contrast, fusions like VGLL2-NCOA2/CITED2, TMP3/TRP-NTRK1 or ETV6-NTRK3 are observed in more heterogeneous tumors. Finally, we also describe a new group of bone sarcomas characterized by EWSR1- or FUS-TFCP2 fusions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-12-14T12:28:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002190","title":"Widespread DNA hypomethylation and differential gene expression in Turner syndrome","description":"Adults with 45,X monosomy (Turner syndrome) reflect a surviving minority since more than 99% of fetuses with 45,X monosomy die in utero. In adulthood 45,X monosomy is associated with increased morbidity and mortality, although strikingly heterogeneous with some individuals left untouched while others suffer from cardiovascular disease, autoimmune disease and infertility. The present study investigates the leukocyte DNAmethylation profile by using the 450K-Illumina Infinium assay and the leukocyte RNA-expression profile in 45,X monosomy compared with karyotypically normal female and male controls. We present results illustrating that genome wide X-chromosome RNA-expression profile, autosomal DNA-methylation profile, and the X-chromosome methylation profile clearly distinguish Turner syndrome from controls. Our results reveal genome wide hypomethylation with most differentially methylated positions showing a medium level of methylation. Contrary to previous studies, applying a single loci specific analysis at well-defined DNA loci, our results indicate that the hypomethylation extend to repetitive elements. We describe novel candidate genes that could be involved in comorbidity in TS and explain congenital urinary malformations (PRKX), premature ovarian failure (KDM6A), and aortic aneurysm formation (ZFYVE9 and TIMP1)","abstract":"Adults with 45,X monosomy (Turner syndrome) reflect a surviving minority since more than 99% of fetuses with 45,X monosomy die in utero. In adulthood 45,X monosomy is associated with increased morbidity and mortality, although strikingly heterogeneous with some individuals left untouched while others suffer from cardiovascular disease, autoimmune disease and infertility. The present study investigates the leukocyte DNAmethylation profile by using the 450K-Illumina Infinium assay and the leukocyte RNA-expression profile in 45,X monosomy compared with karyotypically normal female and male controls. We present results illustrating that genome wide X-chromosome RNA-expression profile, autosomal DNA-methylation profile, and the X-chromosome methylation profile clearly distinguish Turner syndrome from controls. Our results reveal genome wide hypomethylation with most differentially methylated positions showing a medium level of methylation. Contrary to previous studies, applying a single loci specific analysis at well-defined DNA loci, our results indicate that the hypomethylation extend to repetitive elements. We describe novel candidate genes that could be involved in comorbidity in TS and explain congenital urinary malformations (PRKX), premature ovarian failure (KDM6A), and aortic aneurysm formation (ZFYVE9 and TIMP1)","study_type":"Other","pubmed_ids":[27687697],"external_links":null,"is_released":true,"released_date":"2016-12-14T22:38:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002191","title":"Bosma","description":"WES analysis of BAMS patient","abstract":"WES analysis of BAMS patient","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002192","title":"An Unusual Genomic Variant of Pancreatic Ductal Adenocarcinoma with an Indolent Clinical Course","description":"We describe a patient with biopsy-proven locally advanced pancreatic\nductal adenocarcinoma (PDA) who underwent a modified course of\ngemcitabine and stereotactic body radiation therapy. Whole exome\nsequencing of this patient's tumor revealed a simple genome landscape\nwith no evidence of mutations, copy number changes, or structural\nalterations in genes most commonly associated with PDA, i.e. KRAS,\nCDKN2A, TP53 or SMAD4. An analysis of germline DNA revealed no pathogenic\nvariants of significance. Whole exome and whole genome sequencing\nidentified a somatic mutation of RNF213 and an inversion/deletion of\nCTNNA2 as the genetic basis of this PDA.  Although PDA is classically\ncharacterized by a predictable set of mutations, these data suggest that\nalternate genetic paths to PDA may exist, which can be associated with a\nmore indolent clinical course.","abstract":"We describe a patient with biopsy-proven locally advanced pancreatic\nductal adenocarcinoma (PDA) who underwent a modified course of\ngemcitabine and stereotactic body radiation therapy. Whole exome\nsequencing of this patient's tumor revealed a simple genome landscape\nwith no evidence of mutations, copy number changes, or structural\nalterations in genes most commonly associated with PDA, i.e. KRAS,\nCDKN2A, TP53 or SMAD4. An analysis of germline DNA revealed no pathogenic\nvariants of significance. Whole exome and whole genome sequencing\nidentified a somatic mutation of RNF213 and an inversion/deletion of\nCTNNA2 as the genetic basis of this PDA.  Although PDA is classically\ncharacterized by a predictable set of mutations, these data suggest that\nalternate genetic paths to PDA may exist, which can be associated with a\nmore indolent clinical course.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-12-16T22:16:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002193","title":"Whole exome sequencing data for patients with Bosma arhinia microphthalmia syndrome (BAMS).","description":"The datasets includes 21 samples from 7 families with Bosma arhinia microphthalmia (BAMS). For details of the study please refer to the manuscript \"De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development\", Nature Genetics 2017. Each sample was exome sequenced and the family ID in sample description refers to the Individual ID in Supplementary figure 2 of the manuscript.","abstract":"The datasets includes 21 samples from 7 families with Bosma arhinia microphthalmia (BAMS). For details of the study please refer to the manuscript \"De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development\", Nature Genetics 2017. Each sample was exome sequenced and the family ID in sample description refers to the Individual ID in Supplementary figure 2 of the manuscript.","study_type":"Other","pubmed_ids":[28067911],"external_links":null,"is_released":true,"released_date":"2016-12-19T14:34:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002194","title":"NOTUSED:Global Anaplastic Thyroid Cancer Initiative","description":"Thyroid cancer is the most common endocrine malignancy. Most thyroid cancers are of the well-differentiated (non-aggressive) phenotype, and are almost always cured with standard treatments. In contrast, anaplastic thyroid cancer (ATC) is rare, accounting for only 1% of thyroid cancers, however it is perhaps the most lethal human malignancy with an average survival of 3 to 6 months. ATC presents with dramatic and rapid onset of airway and esophageal blockage with frequent spread to the lungs. Interestingly, 21–79% of ATCs have coexisting areas or a previous history of well-differentiated cancers. Although this suggests a progression from well-differentiated cancers to ATC, to date there is little molecular conformation that such a progression exists versus de novo generation of ATC. As ATC is extremely rare and most cases are inoperable, there are a paucity of tissue samples for study at any one center. The Global Anaplastic Thyroid Cancer Initiative (GATCI) aims to unite international institutions in order to pool samples (ATC with or without a paired well-differentiated component) for a comprehensive analysis of the genomic landscape of this disease.","abstract":"Thyroid cancer is the most common endocrine malignancy. Most thyroid cancers are of the well-differentiated (non-aggressive) phenotype, and are almost always cured with standard treatments. In contrast, anaplastic thyroid cancer (ATC) is rare, accounting for only 1% of thyroid cancers, however it is perhaps the most lethal human malignancy with an average survival of 3 to 6 months. ATC presents with dramatic and rapid onset of airway and esophageal blockage with frequent spread to the lungs. Interestingly, 21–79% of ATCs have coexisting areas or a previous history of well-differentiated cancers. Although this suggests a progression from well-differentiated cancers to ATC, to date there is little molecular conformation that such a progression exists versus de novo generation of ATC. As ATC is extremely rare and most cases are inoperable, there are a paucity of tissue samples for study at any one center. The Global Anaplastic Thyroid Cancer Initiative (GATCI) aims to unite international institutions in order to pool samples (ATC with or without a paired well-differentiated component) for a comprehensive analysis of the genomic landscape of this disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002195","title":"Transcriptional mechanisms of resistance to anti-PD-1 therapy","description":"Purpose:  To explore factors associated with response and resistance to anti-PD-1 therapy, we analyzed multiple disease sites at autopsy in a patient with widely metastatic melanoma who had a heterogeneous response.Materials and Methods:  Twenty-six melanoma specimens (four pre-mortem, 22 post-mortem) were subjected to whole-exome sequencing.  Candidate immunologic markers and gene expression were assessed in ten cutaneous metastases showing response or progression during therapy.Results:  The melanoma was driven by biallelic inactivation of NF1.  All lesions had highly concordant mutational profiles and copy number alterations, indicating linear clonal evolution.  Expression of candidate immunologic markers was similar in responding and progressing lesions. However, progressing cutaneous metastases were associated with over-expression of genes associated with extracellular matrix and neutrophil function.Conclusions:  Although mutational and immunologic differences have been proposed as the primary determinants of heterogeneous response/resistance to targeted therapies and immunotherapies, respectively,  differential lesional gene expression profiles may also dictate anti-PD-1 outcomes.","abstract":"Purpose:  To explore factors associated with response and resistance to anti-PD-1 therapy, we analyzed multiple disease sites at autopsy in a patient with widely metastatic melanoma who had a heterogeneous response.Materials and Methods:  Twenty-six melanoma specimens (four pre-mortem, 22 post-mortem) were subjected to whole-exome sequencing.  Candidate immunologic markers and gene expression were assessed in ten cutaneous metastases showing response or progression during therapy.Results:  The melanoma was driven by biallelic inactivation of NF1.  All lesions had highly concordant mutational profiles and copy number alterations, indicating linear clonal evolution.  Expression of candidate immunologic markers was similar in responding and progressing lesions. However, progressing cutaneous metastases were associated with over-expression of genes associated with extracellular matrix and neutrophil function.Conclusions:  Although mutational and immunologic differences have been proposed as the primary determinants of heterogeneous response/resistance to targeted therapies and immunotherapies, respectively,  differential lesional gene expression profiles may also dictate anti-PD-1 outcomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-12-20T17:50:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002196","title":"There are 33 Blood cancer cases in this study and belong to LAML-CN project.","description":"There are 33 Blood cancer cases in this study and belong to LAML-CN project.","abstract":"There are 33 Blood cancer cases in this study and belong to LAML-CN project.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002197","title":"Oncogenic gene fusions in primary colon cancers","description":"This study represents RNA-sequencing data from 278 primary colon cancers obtained from fresh-frozen tumor sections. The project goal was to identify novel oncogenic gene fusions in these data. In addition, we studied the detected gene fusions at the molecular level and defined their effects on downstream pathways.","abstract":"This study represents RNA-sequencing data from 278 primary colon cancers obtained from fresh-frozen tumor sections. The project goal was to identify novel oncogenic gene fusions in these data. In addition, we studied the detected gene fusions at the molecular level and defined their effects on downstream pathways.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-12-21T11:11:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002198","title":"The genomic landscape of Burkitt Lymphoma","description":"As part of the ICGC, the ICGC MMML-Seq project performed whole genome sequencing and RNA sequencing of Burkitt Lymphomas . Burkitt lymphomas are the most common B-cell lymphomas in childhood. Analyses were performed in concordance with the guidelines of the ICGC. The results define the genomic landscape of structural variants, somatic single nucleotide variants and mutational signatures in these lymphomas.","abstract":"As part of the ICGC, the ICGC MMML-Seq project performed whole genome sequencing and RNA sequencing of Burkitt Lymphomas . Burkitt lymphomas are the most common B-cell lymphomas in childhood. Analyses were performed in concordance with the guidelines of the ICGC. The results define the genomic landscape of structural variants, somatic single nucleotide variants and mutational signatures in these lymphomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-12-22T08:28:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002199","title":"The genomic landscape of follicular and diffuse large B-cell lymphoma","description":"As part of the ICGC, the ICGC MMML-Seq project performed whole genome sequencing and RNA sequencing of follicular and diffuse large B-cell lymphoma. Follicular and diffuse large B-cell lymphomas are the most common B-cell lymphomas in adulthood. Analyses were performed in concordance with the guidelines of the ICGC. The results define the genomic landscape of structural variants, somatic single nucleotide variants and mutational signatures in these lymphomas","abstract":"As part of the ICGC, the ICGC MMML-Seq project performed whole genome sequencing and RNA sequencing of follicular and diffuse large B-cell lymphoma. Follicular and diffuse large B-cell lymphomas are the most common B-cell lymphomas in adulthood. Analyses were performed in concordance with the guidelines of the ICGC. The results define the genomic landscape of structural variants, somatic single nucleotide variants and mutational signatures in these lymphomas","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-12-22T08:32:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002200","title":"Comprehensive analyses of somatic TP53 mutation in tumors with variable mutant allele frequency","description":"Somatic mutation of the tumor suppressor gene TP53 is reported in at least 50% of human malignancies. Most high-grade serous ovarian cancers (HGSC) have a mutant TP53 allele. Accurate detection of these mutants in heterogeneous tumor tissue is paramount as therapies emerge to target mutant p53. We used a Fluidigm Access Array™ System with Massively Parallel Sequencing (MPS) to analyze DNA extracted from 76 serous ovarian tumors. This dataset has been made available to researchers through the European Genome-phenome Archive (EGA). Herein, we present detailed analyses of this dataset using HaplotypeCaller and MuTect2 through the Broad Institute’s Genome Analysis Toolkit (GATK). We also present comparisons of the ability to detect TP53 mutation by MPS and Sanger sequencing in these tumors. We anticipate that this TP53 mutation dataset will be useful to researchers developing and testing new software to accurately determine high and low frequency variant alleles in heterogeneous aneuploid tumor tissue. Further, the analysis pipeline we present provides a valuable framework for determining somatic variants more broadly in tumor tissue.","abstract":"Somatic mutation of the tumor suppressor gene TP53 is reported in at least 50% of human malignancies. Most high-grade serous ovarian cancers (HGSC) have a mutant TP53 allele. Accurate detection of these mutants in heterogeneous tumor tissue is paramount as therapies emerge to target mutant p53. We used a Fluidigm Access Array™ System with Massively Parallel Sequencing (MPS) to analyze DNA extracted from 76 serous ovarian tumors. This dataset has been made available to researchers through the European Genome-phenome Archive (EGA). Herein, we present detailed analyses of this dataset using HaplotypeCaller and MuTect2 through the Broad Institute’s Genome Analysis Toolkit (GATK). We also present comparisons of the ability to detect TP53 mutation by MPS and Sanger sequencing in these tumors. We anticipate that this TP53 mutation dataset will be useful to researchers developing and testing new software to accurately determine high and low frequency variant alleles in heterogeneous aneuploid tumor tissue. Further, the analysis pipeline we present provides a valuable framework for determining somatic variants more broadly in tumor tissue.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2016-12-27T12:38:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002201","title":"THAP11 mutations in a patient with a cblX-like phenotype implicates THAP11 in the regulation of cobalamin metabolism and early vertebrate development","description":"Mutations in HCFC1 are associated with cblX (MIM309541), an X-linked recessive disorder, characterized by defects in cobalamin metabolism and other developmental defects. HCFC1 is a transcriptional co-regulator, which interacts with transcription factors to regulate the expression of a myriad of genes. Notably, HCFC1 regulates cobalamin metabolism via the regulation of MMACHC expression through its interaction with THAP11, a THAP domain-containing transcription factor. In addition, the HCFC1/THAP11 complex potentially regulates genes involved in diverse cellular functions including cell cycle, proliferation, and transcription. Thus, it is likely that mutations in THAP11 may also result in biochemical and other phenotypes similar to those observed in patients with cblX. We report a patient who presented with phenotypic features that overlap cblX, but did not have any mutations in either MMACHC or HCFC1. We sequenced THAP11 by Sanger sequencing and discovered a potentially pathogenic, homozygous variant in THAP11, c.240C&gt;G (p.Phe80Leu). Functional analysis in the developing zebrafish embryo, demonstrate that both THAP11 and HCFC1 regulate the proliferation and differentiation of neural precursors, suggesting important roles in normal brain development. Further, the loss of THAP11 in zebrafish embryos, results in craniofacial abnormalities including the complete loss of Meckel’s cartilage, the ceratohyal, and all of the ceratobranchial cartilages. These data are consistent with our previous work which demonstrated a role for HCFC1 in vertebrate craniofacial development. Furthermore, our high throughput RNA-sequencing analysis reveals several overlapping gene targets of HCFC1 and THAP11 that likely contribute to the phenotypes associated with cblX and related disorders. Thus, both HCFC1 and THAP11 play important roles in the regulation of cobalamin metabolism as well as other pathways involved in early vertebrate development.","abstract":"Mutations in HCFC1 are associated with cblX (MIM309541), an X-linked recessive disorder, characterized by defects in cobalamin metabolism and other developmental defects. HCFC1 is a transcriptional co-regulator, which interacts with transcription factors to regulate the expression of a myriad of genes. Notably, HCFC1 regulates cobalamin metabolism via the regulation of MMACHC expression through its interaction with THAP11, a THAP domain-containing transcription factor. In addition, the HCFC1/THAP11 complex potentially regulates genes involved in diverse cellular functions including cell cycle, proliferation, and transcription. Thus, it is likely that mutations in THAP11 may also result in biochemical and other phenotypes similar to those observed in patients with cblX. We report a patient who presented with phenotypic features that overlap cblX, but did not have any mutations in either MMACHC or HCFC1. We sequenced THAP11 by Sanger sequencing and discovered a potentially pathogenic, homozygous variant in THAP11, c.240C&gt;G (p.Phe80Leu). Functional analysis in the developing zebrafish embryo, demonstrate that both THAP11 and HCFC1 regulate the proliferation and differentiation of neural precursors, suggesting important roles in normal brain development. Further, the loss of THAP11 in zebrafish embryos, results in craniofacial abnormalities including the complete loss of Meckel’s cartilage, the ceratohyal, and all of the ceratobranchial cartilages. These data are consistent with our previous work which demonstrated a role for HCFC1 in vertebrate craniofacial development. Furthermore, our high throughput RNA-sequencing analysis reveals several overlapping gene targets of HCFC1 and THAP11 that likely contribute to the phenotypes associated with cblX and related disorders. Thus, both HCFC1 and THAP11 play important roles in the regulation of cobalamin metabolism as well as other pathways involved in early vertebrate development.","study_type":"Other","pubmed_ids":[28449119],"external_links":null,"is_released":true,"released_date":"2016-12-31T02:14:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002202","title":"Genomic Landscape of Pediatric Myelodysplastic Syndromes","description":"Pediatric myelodysplastic syndromes (MDS) are a rare disease and unlike their adult counterpart, very little is known about their genomic landscape.  We characterized a cohort of patients from a single institution by whole exome sequencing, as well as a subset of patients by whole genome sequencing, RNA-sequencing and targeted deep sequencing.  We found a spectrum of mutations, both somatic and germline, that are distinct from those observed in adult MDS.  In turn, we observed mutations commonly observed in other pediatric myeloid tumors.","abstract":"Pediatric myelodysplastic syndromes (MDS) are a rare disease and unlike their adult counterpart, very little is known about their genomic landscape.  We characterized a cohort of patients from a single institution by whole exome sequencing, as well as a subset of patients by whole genome sequencing, RNA-sequencing and targeted deep sequencing.  We found a spectrum of mutations, both somatic and germline, that are distinct from those observed in adult MDS.  In turn, we observed mutations commonly observed in other pediatric myeloid tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-03T14:53:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002203","title":"Phenotypic and Transcriptional Profiling Reveals Functionally Distinct Monocyte-related Dendritic Cells in the Steady-State Human Intestine","description":"The tissue dendritic cell (DC) compartment is heterogeneous, and the ontogeny and functional specialization of human tissue conventional DC (cDC) subsets and their relationship with monocytes is unresolved. Here we identify monocyte-related CSF1R+Flt3- DCs that constitute about half of the SIRPα+ DCs in the steady-state human small intestine. CSF1R+Flt3- DCs express calprotectin and very low levels of CD14, are transcriptionally related to monocytes-derived cells, and accumulate during inflammation. CSF1R+Flt3- DCs are functionally distinct from their Flt3+ cDC counterparts: under steady-state conditions they excel at antigen uptake, show lower migratory potential, and are inefficient activators of naïve T cells. These results have important implications for the understanding of the ontogenetic and functional heterogeneity within human tissue DCs.","abstract":"The tissue dendritic cell (DC) compartment is heterogeneous, and the ontogeny and functional specialization of human tissue conventional DC (cDC) subsets and their relationship with monocytes is unresolved. Here we identify monocyte-related CSF1R+Flt3- DCs that constitute about half of the SIRPα+ DCs in the steady-state human small intestine. CSF1R+Flt3- DCs express calprotectin and very low levels of CD14, are transcriptionally related to monocytes-derived cells, and accumulate during inflammation. CSF1R+Flt3- DCs are functionally distinct from their Flt3+ cDC counterparts: under steady-state conditions they excel at antigen uptake, show lower migratory potential, and are inefficient activators of naïve T cells. These results have important implications for the understanding of the ontogenetic and functional heterogeneity within human tissue DCs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002204","title":"The_identification_of_genetic_vulnerabilities_in_head_and_neck_cancers_for_the_development_of_novel_therapies","description":"CRISPR/Cas9 lethality screens in a set of Asian head and neck cancer cell lines to identify novel targets.","abstract":"The global cancer burden is expected to double by the year 2030 and this will disproportionately affect the Asian continent. Head and neck squamous cell carcinoma (HNSCC) is endemic in Asia. It is the sixth most common cancer worldwide and the second most common in Malaysia, with approximately 600,000 new cases per year globally. Longterm survival remains less than 50%, underscoring the need for better therapeutic strategies. In this proposal we aim to bring new technological advancements in the identification of critical genes in HNSCC and the identification of compounds for the development of new therapies in HNSCC. We propose to identify essential genes in HNSCC that can be targeted for tumor control. Further, we propose to use zebrafish, an established drug discovery platform to identify promising pathway-specific compounds that could be further studied using CRISPR/Cas9 lethality screens and biological models to better identify novel therapeutic strategies to combat this major health problem in Asia.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-05T14:04:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002205","title":"Genomic data from analysis of the human placenta, part of the Pregnancy Outcome Prediction study (POPs)","description":"The Pregnancy Outcome Prediction (POP) study is a prospective cohort study of nulliparous women attending the Rosie Hospital (Cambridge, UK) for their dating ultrasound scan. The study included 4512 women with a viable singleton pregnancy; study participants provided written informed consent and were recruited between January 2008 and July 2012. The POP study aimed both at evaluating performance of known biomarkers and serial ultrasonography in assessing maternal and fetal well-being, as well as identifying novel biomarkers. The study is sufficiently large to be powered for relatively uncommon adverse pregnancy outcomes. Women attended four study visits scheduled every 8 weeks, starting with the first trimester. Participants had blood taken during the dating/recruitment visit (at approximately 12 weeks gestation (wkGA)), as well as at three subsequent visits (at ∼20wkGA, ∼28wkGA and ∼36wkGA). For more detail, please visit: https://www.obgyn.cam.ac.uk/research/pops-2/.","abstract":"The Pregnancy Outcome Prediction (POP) study is a prospective cohort study of nulliparous women attending the Rosie Hospital (Cambridge, UK) for their dating ultrasound scan. The study included 4512 women with a viable singleton pregnancy; study participants provided written informed consent and were recruited between January 2008 and July 2012. The POP study aimed both at evaluating performance of known biomarkers and serial ultrasonography in assessing maternal and fetal well-being, as well as identifying novel biomarkers. The study is sufficiently large to be powered for relatively uncommon adverse pregnancy outcomes. Women attended four study visits scheduled every 8 weeks, starting with the first trimester. Participants had blood taken during the dating/recruitment visit (at approximately 12 weeks gestation (wkGA)), as well as at three subsequent visits (at ∼20wkGA, ∼28wkGA and ∼36wkGA). For more detail, please visit: https://www.obgyn.cam.ac.uk/research/pops-2/.","study_type":"Other","pubmed_ids":[26360240,29376485,29997303,31367035,32367053],"external_links":null,"is_released":true,"released_date":"2017-01-05T16:34:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002206","title":"Spectrum and significance of MYC and BCL2 mutations in DLBCL","description":"We analyzed the spectrum and clinical significance of MYC and BCL2 mutations in 347 DLBCL cases from population-based cohort of BC, Canada. Mutational status of MYC and BCL2 coding exons were sequenced using TSCA assay.","abstract":"We analyzed the spectrum and clinical significance of MYC and BCL2 mutations in 347 DLBCL cases from population-based cohort of BC, Canada. Mutational status of MYC and BCL2 coding exons were sequenced using TSCA assay.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-06T23:37:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002207","title":"Circumventing intratumoral heterogeneity to identify potential therapeutic targets in hepatocellular carcinoma. Details please contact lifuqiang@genomics and zhaoxin@genomics.cn.","description":"Background and aims: Intratumoral heterogeneity (ITH) challenges identifying mutations with target therapy potential whereas circulating cell-free DNAs (cfDNAs) could reflect nearly the entire mutation spectrum in given tumors. We investigated how to minimize the limit of ITH for profiling hepatocellular carcinoma (HCC).Methods: Thirty-two multi-regional HCC samples from five patients were subjected to whole exome sequencing (WES) and targeted deep sequencing (TDS). ITH extent was measured by the average percentage of non-ubiquitous mutations (present in parts of tumor regions). Matched cfDNAs were also analyzed by WES and TDS. Profiling efficiencies of single tumor specimen and cfDNA were compared and the one better depicted mutational landscape was selected to screen therapeutic targets.Results: We found variable extents of ITH in HCCs and observed branched and parallel evolution patterns. ITH level decreased at higher sequencing depth of TDS than that measured by WES (28.1% vs 34.9%, P &lt; 0.01) but it remained unchanged upon additional samples analyzed. TDS of single tumor specimen detected an average of 70% the total mutations in HCC. Although more mutations were detected in cfDNA under TDS than WES, an average of 47.2% total HCC mutations uncovered by cfDNA suggested tissue outperform cfDNA and the latter may serve as alternative in profiling HCC genome. Consequently, TDS of single tumor tissue in 66 patients and cfDNAs in four unresectable HCCs identified 38.6% (26/66 and 1/4) patients bearing therapeutic targets.Conclusions: TDS of single tumor specimen could largely circumvent ITH to uncover mutations indicative of target therapy in HCC.","abstract":"Background and aims: Intratumoral heterogeneity (ITH) challenges identifying mutations with target therapy potential whereas circulating cell-free DNAs (cfDNAs) could reflect nearly the entire mutation spectrum in given tumors. We investigated how to minimize the limit of ITH for profiling hepatocellular carcinoma (HCC).Methods: Thirty-two multi-regional HCC samples from five patients were subjected to whole exome sequencing (WES) and targeted deep sequencing (TDS). ITH extent was measured by the average percentage of non-ubiquitous mutations (present in parts of tumor regions). Matched cfDNAs were also analyzed by WES and TDS. Profiling efficiencies of single tumor specimen and cfDNA were compared and the one better depicted mutational landscape was selected to screen therapeutic targets.Results: We found variable extents of ITH in HCCs and observed branched and parallel evolution patterns. ITH level decreased at higher sequencing depth of TDS than that measured by WES (28.1% vs 34.9%, P &lt; 0.01) but it remained unchanged upon additional samples analyzed. TDS of single tumor specimen detected an average of 70% the total mutations in HCC. Although more mutations were detected in cfDNA under TDS than WES, an average of 47.2% total HCC mutations uncovered by cfDNA suggested tissue outperform cfDNA and the latter may serve as alternative in profiling HCC genome. Consequently, TDS of single tumor tissue in 66 patients and cfDNAs in four unresectable HCCs identified 38.6% (26/66 and 1/4) patients bearing therapeutic targets.Conclusions: TDS of single tumor specimen could largely circumvent ITH to uncover mutations indicative of target therapy in HCC.","study_type":"Other","pubmed_ids":[28323123],"external_links":null,"is_released":true,"released_date":"2017-01-09T05:11:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002208","title":"Alternative_Enzymes_screen_2017","description":"Test of enzymes for Illumina library prep PCR","abstract":"Test of enzymes for Illumina library prep PCR","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002209","title":"Whole exome sequencing of a family with high penetrance of monoclonal gammopathies","description":"We describe a family with high penetrance of plasma-cell dyscrasias, suggestive of inheritance of an autosomal dominant risk allele. We performed whole exome sequencing (WES) in 3 affected members of the family, and one healthy one. We report on a combined approach aimed at the identification of causative variants and risk loci, exploiting the wealth of data provided by this approach and an additional dataset of multiple myeloma patients and healthy controls. We identified gene mutations and SNPs of potential significance, and pinpointed to known risk locus for myeloma as the potential area of transmissible risk in the family. Our study provides the first WES approach to such cases, and a framework of analysis that could be applied to further the understanding of inherited risk of developing plasma-cell dyscrasias.","abstract":"We describe a family with high penetrance of plasma-cell dyscrasias, suggestive of inheritance of an autosomal dominant risk allele. We performed whole exome sequencing (WES) in 3 affected members of the family, and one healthy one. We report on a combined approach aimed at the identification of causative variants and risk loci, exploiting the wealth of data provided by this approach and an additional dataset of multiple myeloma patients and healthy controls. We identified gene mutations and SNPs of potential significance, and pinpointed to known risk locus for myeloma as the potential area of transmissible risk in the family. Our study provides the first WES approach to such cases, and a framework of analysis that could be applied to further the understanding of inherited risk of developing plasma-cell dyscrasias.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002210","title":"Targeted_sequencing_of_blood_DNA_from_Human_twins_","description":"The goals of this study is to investigate the prevalence and heritability of age-related clonal haemopoeisis (ARCH) in healthy elderly individuals.We will use a bespoke bait set to pull down DNA regions of interest in whole blood samples combined with HiSeq at a deep level . By correlating findings from each individual to their respective twin we hope to elucidate whether heritable traits influence the development of ARCH.     \na.\tThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The goals of this study is to investigate the prevalence and heritability of age-related clonal haemopoeisis (ARCH) in healthy elderly individuals.We will use a bespoke bait set to pull down DNA regions of interest in whole blood samples combined with HiSeq at a deep level . By correlating findings from each individual to their respective twin we hope to elucidate whether heritable traits influence the development of ARCH.     \na.\tThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-09T15:51:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002211","title":"CancerLocator: Non-Invasive Cancer Diagnosis and Tissue-of-Origin Prediction Using Methylation Profiles of Cell-Free DNA","description":"Background: The detection and characterization of cell-free DNA in plasma is one of the most promising new areas in cancer diagnosis. Liquid biopsy, unlike traditional tissue biopsy, has the potential to diagnose a variety of different malignancies. Results: Here we propose a probabilistic method, CancerLocator, which exploits the diagnostic potential of cell-free DNA by determining not only the presence but also the location of tumors. CancerLocator simultaneously infers the proportions and the tissue-of-origin of tumor-derived cell-free DNA in a blood sample using genome-wide DNA methylation data. We comprehensively evaluate CancerLocator with simulations and real data, and compare its performance with that of two established multi-class classification methods. We show that the predicted tumor burdens are highly consistent with the true values. In addition, when the proportion of tumor-derived DNAs in the cell-free DNAs is low, the two popular machine learning methods completely fail for cancer diagnosis, while CancerLocator successfully overcomes the challenge. CancerLocator also achieves promising results on patient plasma samples, despite the fact that the DNA methylation data from these samples has very low sequencing coverage. Conclusions: CfDNA methylation may be developed as an important approach for non-invasive early cancer diagnosis.","abstract":"Background: The detection and characterization of cell-free DNA in plasma is one of the most promising new areas in cancer diagnosis. Liquid biopsy, unlike traditional tissue biopsy, has the potential to diagnose a variety of different malignancies. Results: Here we propose a probabilistic method, CancerLocator, which exploits the diagnostic potential of cell-free DNA by determining not only the presence but also the location of tumors. CancerLocator simultaneously infers the proportions and the tissue-of-origin of tumor-derived cell-free DNA in a blood sample using genome-wide DNA methylation data. We comprehensively evaluate CancerLocator with simulations and real data, and compare its performance with that of two established multi-class classification methods. We show that the predicted tumor burdens are highly consistent with the true values. In addition, when the proportion of tumor-derived DNAs in the cell-free DNAs is low, the two popular machine learning methods completely fail for cancer diagnosis, while CancerLocator successfully overcomes the challenge. CancerLocator also achieves promising results on patient plasma samples, despite the fact that the DNA methylation data from these samples has very low sequencing coverage. Conclusions: CfDNA methylation may be developed as an important approach for non-invasive early cancer diagnosis.","study_type":"Other","pubmed_ids":[28335812],"external_links":null,"is_released":true,"released_date":"2017-01-09T23:11:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002212","title":"Whole-genome low pass sequencing of 3,514 Sardinian individuals","description":"The dataset includes the VCF files with the list of variants, and their frequency, found in 3,514 Sardinian individuals recruited from the SardiNIA longitudinal study (N=2090) and from a case-control study of autoimmune diseases in Sardinia (N=1424).","abstract":"The dataset includes the VCF files with the list of variants, and their frequency, found in 3,514 Sardinian individuals recruited from the SardiNIA longitudinal study (N=2090) and from a case-control study of autoimmune diseases in Sardinia (N=1424).","study_type":"Other","pubmed_ids":[26366554],"external_links":null,"is_released":true,"released_date":"2017-01-10T13:02:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002213","title":"Same-day genomic and epigenomic diagnosis of brain tumors using realtime nanopore sequencing","description":"Molecular classification of cancer has entered clinical routine to inform diagnosis, prognosis and treatment decisions. At the same time, new tumor entities have been identified that cannot be defined histologically. For central nervous systems tumors, the current World Health Organization classification explicitly demands molecular testing, e.g. for 1p/19q- codeletion or IDH mutations, to make an integrated histomolecular diagnosis. However, a plethora of sophisticated technologies is currently needed to assess different genomic and epigenomic alterations and turnaround times are in the range of weeks, which makes standardized and widespread implementation difficult and hinders timely decision making. Here, we explored the potential of a pocket-size nanopore sequencing device for multimodal and rapid molecular diagnostics of cancer. Low-pass whole genome sequencing was used to simultaneously generate copy number (CN) and methylation profiles from native tumor DNA in the same sequencing run. Single nucleotide variants in IDH1, IDH2, TP53, H3F3A and the TERT promoter region were identified using deep amplicon sequencing. Nanopore sequencing yielded ~0.1X genome coverage within six hours and resulting CN and epigenetic profiles correlated well with matched microarray data. Diagnostically relevant alterations, such as 1p/19q codeletion, and focal amplifications could be recapitulated. Using ad hoc random forests, we could perform supervised pan-cancer classification to distinguish gliomas, medulloblastomas and brain metastases of different primary sites. Single nucleotide variants in IDH1, IDH2 and H3F3A were identified using deep amplicon sequencing within minutes of sequencing. Detection of TP53 and TERT promoter mutations shows that sequencing of entire genes and GC-rich regions is feasible. Nanopore sequencing allows same-day detection of structural variants, point mutations and methylation profiling using a single device with negligible capital cost. It outperforms hybridization-based and current sequencing technologies with respect to time-to diagnosis and required laboratory equipment and expertise, aiming to make precision medicine possible for every cancer patient, even in resource restricted settings.","abstract":"Molecular classification of cancer has entered clinical routine to inform diagnosis, prognosis and treatment decisions. At the same time, new tumor entities have been identified that cannot be defined histologically. For central nervous systems tumors, the current World Health Organization classification explicitly demands molecular testing, e.g. for 1p/19q- codeletion or IDH mutations, to make an integrated histomolecular diagnosis. However, a plethora of sophisticated technologies is currently needed to assess different genomic and epigenomic alterations and turnaround times are in the range of weeks, which makes standardized and widespread implementation difficult and hinders timely decision making. Here, we explored the potential of a pocket-size nanopore sequencing device for multimodal and rapid molecular diagnostics of cancer. Low-pass whole genome sequencing was used to simultaneously generate copy number (CN) and methylation profiles from native tumor DNA in the same sequencing run. Single nucleotide variants in IDH1, IDH2, TP53, H3F3A and the TERT promoter region were identified using deep amplicon sequencing. Nanopore sequencing yielded ~0.1X genome coverage within six hours and resulting CN and epigenetic profiles correlated well with matched microarray data. Diagnostically relevant alterations, such as 1p/19q codeletion, and focal amplifications could be recapitulated. Using ad hoc random forests, we could perform supervised pan-cancer classification to distinguish gliomas, medulloblastomas and brain metastases of different primary sites. Single nucleotide variants in IDH1, IDH2 and H3F3A were identified using deep amplicon sequencing within minutes of sequencing. Detection of TP53 and TERT promoter mutations shows that sequencing of entire genes and GC-rich regions is feasible. Nanopore sequencing allows same-day detection of structural variants, point mutations and methylation profiling using a single device with negligible capital cost. It outperforms hybridization-based and current sequencing technologies with respect to time-to diagnosis and required laboratory equipment and expertise, aiming to make precision medicine possible for every cancer patient, even in resource restricted settings.","study_type":"Other","pubmed_ids":[28638988],"external_links":null,"is_released":true,"released_date":"2017-01-10T15:24:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002214","title":"Effect_of_WGA_lysis_buffers_on_substitution_profiles","description":"Whole genome amplification of DNA from ESS1 using a variety of lysis conditions.","abstract":"ESS1 has a specific mutational profile (signature 10) that can be used to distinguish somatic mutations from MDA artefacts.  Signature 10 is defined by C&gt;T mutations at TCG and C&gt;A mutations at TCT. The effect of different lysis and amplification methods on erorr profiles during MDA.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002215","title":"Warm_autopsy_Liver_LMC__G_T_RNA_pilot","description":"To study the transcriptome of different area of a liver nobules","abstract":"To study the transcriptome of different area of a liver nobules","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002216","title":"Warm_autopsy__mutational_signatures_and_clonal_units","description":"Aims and objectives\n\n1.\tTo produce a ‘first generation map’ of mutational burdens and mutational processes that operate in normal human tissues. \n2.\tTo examine clonal units and their distribution across normal human tissues with the emphasis on these particular areas:\na)\tTissues with an architecturally defined unit: Are architectural structures populated by a progeny derived from a single stem cell? Are clonal units confined to a given architectural structure? Examples of tissues where such approach will be used include prostate gland (acini and ducts), small bowel (crypts), thyroid gland (follicles) and others. \nb)\tTissues without an architecturally defined unit: What is the average size of clonal populations? This group includes stratified/pseudostratified epithelia with a basal layer within which there are stem cells that give rise to a progeny of cells showing upwards migration and lateral expansion (e.g. urothelium, cervical squamous epithelium, respiratory epithelium). This approach can also be used in tissues with a sheet-like cell arrangement, for example brain and adrenal gland.\n\nMethods\n\nTo answer these questions, we will use a range of normal human tissue samples which have already been collected from a single deceased individual. The samples are currently stored in a -80C freezer. Ethanol fixed frozen sections will be prepared from these biopsies. Putative clonal units will be identified and dissected out using laser capture microscopy. DNA extraction will be performed using the in-house (CGP) protease based method.\n\nIn terms of sequencing methods, the project will be split into 2 phases (2 different approaches):\n\n-\tPhase 1: This part of the project will utilise a combination of low input library preparation (developed by Peter Ellis) and standard whole genome sequencing (HiSeqX). The phase has already started (December 2016). \nThis approach will be particularly useful in investigation of mitotically active tissues.\n-\tPhase 2: This part of the project will utilise a combination of low input library method (Peter Ellis) and Bottle-neck sequencing (BotSeqS). BotSeqS is a type of duplex sequencing method that offers a more accurate variant calling and allows genome interrogation at a single cell level. This method is currently being developed and is expected to be implemented in 3-6 months (March-April 2017). This approach will be particularly useful for post-mitotic tissues and tissues without pre-defined architectural units.","abstract":"Aims and objectives\n\n1.\tTo produce a ‘first generation map’ of mutational burdens and mutational processes that operate in normal human tissues. \n2.\tTo examine clonal units and their distribution across normal human tissues with the emphasis on these particular areas:\na)\tTissues with an architecturally defined unit: Are architectural structures populated by a progeny derived from a single stem cell? Are clonal units confined to a given architectural structure? Examples of tissues where such approach will be used include prostate gland (acini and ducts), small bowel (crypts), thyroid gland (follicles) and others. \nb)\tTissues without an architecturally defined unit: What is the average size of clonal populations? This group includes stratified/pseudostratified epithelia with a basal layer within which there are stem cells that give rise to a progeny of cells showing upwards migration and lateral expansion (e.g. urothelium, cervical squamous epithelium, respiratory epithelium). This approach can also be used in tissues with a sheet-like cell arrangement, for example brain and adrenal gland.\n\nMethods\n\nTo answer these questions, we will use a range of normal human tissue samples which have already been collected from a single deceased individual. The samples are currently stored in a -80C freezer. Ethanol fixed frozen sections will be prepared from these biopsies. Putative clonal units will be identified and dissected out using laser capture microscopy. DNA extraction will be performed using the in-house (CGP) protease based method.\n\nIn terms of sequencing methods, the project will be split into 2 phases (2 different approaches):\n\n-\tPhase 1: This part of the project will utilise a combination of low input library preparation (developed by Peter Ellis) and standard whole genome sequencing (HiSeqX). The phase has already started (December 2016). \nThis approach will be particularly useful in investigation of mitotically active tissues.\n-\tPhase 2: This part of the project will utilise a combination of low input library method (Peter Ellis) and Bottle-neck sequencing (BotSeqS). BotSeqS is a type of duplex sequencing method that offers a more accurate variant calling and allows genome interrogation at a single cell level. This method is currently being developed and is expected to be implemented in 3-6 months (March-April 2017). This approach will be particularly useful for post-mitotic tissues and tissues without pre-defined architectural units.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-11T13:19:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002217","title":"Clinical Cancer Genomic Profiling by Three-Platform Sequencing of Whole Genome, Whole Exome and Transcriptome","description":"To evaluate the potential of an integrated clinical test to detect diverse classes of somatic and germline mutations relevant to pediatric oncology, we performed three-platform whole-genome (WGS), whole exome (WES) and transcriptome (RNA-Seq) sequencing of tumors and normal tissue from 78 pediatric cancer patients in a CLIA-certified, CAP-accredited laboratory. Our analysis pipeline achieves high accuracy by cross-validating variants between sequencing types, thereby removing the need for confirmatory testing, and facilitates comprehensive reporting in a clinically-relevant timeframe. Three-platform sequencing has a positive predictive value of 97-99%, 99% and 91% for somatic SNVs, indels and structural variations, respectively, based on independent experimental verification of 15,225 variants. We report 240 pathogenic variants across all cases, including 84 of 86 known from previous diagnostic testing (98% sensitivity). Combined WES and RNA-Seq, the current standard for precision oncology, achieved only 78% sensitivity. These results emphasize the critical need for incorporating WGS in pediatric oncology testing.","abstract":"To evaluate the potential of an integrated clinical test to detect diverse classes of somatic and germline mutations relevant to pediatric oncology, we performed three-platform whole-genome (WGS), whole exome (WES) and transcriptome (RNA-Seq) sequencing of tumors and normal tissue from 78 pediatric cancer patients in a CLIA-certified, CAP-accredited laboratory. Our analysis pipeline achieves high accuracy by cross-validating variants between sequencing types, thereby removing the need for confirmatory testing, and facilitates comprehensive reporting in a clinically-relevant timeframe. Three-platform sequencing has a positive predictive value of 97-99%, 99% and 91% for somatic SNVs, indels and structural variations, respectively, based on independent experimental verification of 15,225 variants. We report 240 pathogenic variants across all cases, including 84 of 86 known from previous diagnostic testing (98% sensitivity). Combined WES and RNA-Seq, the current standard for precision oncology, achieved only 78% sensitivity. These results emphasize the critical need for incorporating WGS in pediatric oncology testing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-11T21:32:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002218","title":"The Landscape of Genetic Alterations in Hepatocellular Carcinoma, 88 matched HCC tumour/normal pairs WGS belongs to ICGC LICA-CN project","description":"Hepatocellular carcinoma (HCC) is the most common malignancy of the liver. Genomic analysis is conducted to identify genetic alterations in driver genes which are all druggable targets for cancer therapy.\nWhole genome shotgun sequencing (WGS) and the landscaple of somatic mutations in 88 paired samples from HCC patients including tumors and matched adjacent normal tissues using Illumina HiSeq 2000 platform were performed.","abstract":"Hepatocellular carcinoma (HCC) is the most common malignancy of the liver. Genomic analysis is conducted to identify genetic alterations in driver genes which are all druggable targets for cancer therapy.\nWhole genome shotgun sequencing (WGS) and the landscaple of somatic mutations in 88 paired samples from HCC patients including tumors and matched adjacent normal tissues using Illumina HiSeq 2000 platform were performed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-12T08:58:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002219","title":"Combination_Therapies_for_Personalised_Cancer_Medicine_in_EGFR_mutant_lung_cancer__WES","description":"This study involves mutagenizing a range of different cell lines with ENU to identify those mutations which engender resistance to targeted treatment.","abstract":"In the last decade we have begun to move towards the use of targeted therapeutics in the clinic, often resulting in dramatic response rates in cancer patients. However, clinical experience has demonstrated time and time again that such responses are invariably followed by the development of drug resistance. Identification of the underlying mechanisms may enable us to reverse such resistance. Traditional methods of modelling this resistance in vitro can lead to a plethora of potential resistance mechanisms that can be difficult to decipher.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002220","title":"HipSci_RNASEQ_PID","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from patients with primary immune deficiency","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies.  In this sub-study we perform RNAseq on iPS lines from primary immune deficiency patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002221","title":"Organoid_Derivation_Project__TGS","description":"Sequencing of tissue samples and their derived organoids from oesophageal, pancreatic and colorectal cancer patients.","abstract":"Generation of normal and cancer organoids for sequencing as part of the WTSI-CRUK international collaboration with NCI (in HCMI) to generate the next generation of cancer cell lines.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-12T11:32:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002222","title":"Organoid_Derivation_Project__WGS","description":"Generation of normal and cancer organoids for sequencing as part of the WTSI-CRUK international collaboration with NCI (in HCMI) to generate the next generation of cancer cell lines","abstract":"Generation of normal and cancer organoids for sequencing as part of the WTSI-CRUK international collaboration with NCI (in HCMI) to generate the next generation of cancer cell lines","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-12T11:36:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002223","title":"Organoid_Derivation_Pilot__RNAseq","description":"Generation of normal and cancer organoids for sequencing as part of the WTSI-CRUK international collaboration with NCI (in HCMI) to generate the next generation of cancer cell lines.","abstract":"Generation of normal and cancer organoids for sequencing as part of the WTSI-CRUK international collaboration with NCI (in HCMI) to generate the next generation of cancer cell lines.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-12T11:42:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002224","title":"DONSON encodes a novel replication fork protection factor mutated in microcephalic dwarfism.","description":"To ensure efficient genome duplication, cells have evolved a multitude of factors that promote unperturbed DNA replication, and protect, repair and restart damaged forks. Here we identify DONSON as a novel fork protection factor, and report biallelic DONSON mutations in 29 individuals with microcephalic dwarfism. We demonstrate that DONSON is a component of the replisome that stabilises forks during normal genome replication. Loss of DONSON leads to severe replication-associated DNA damage arising from nucleolytic cleavage of stalled replication forks. Furthermore, ATR-dependent signalling in response to replication stress is impaired in DONSON-deficient cells, resulting in decreased checkpoint activity, and potentiating chromosomal instability. Hypomorphic mutations substantially reduce DONSON protein levels and impair fork stability in patient cells, consistent with defective DNA replication underlying the disease phenotype. In summary, we identify mutations in DONSON as a common cause of microcephalic dwarfism, and establish DONSON as a critical replication fork protein required for mammalian DNA replication and genome stability.","abstract":"To ensure efficient genome duplication, cells have evolved a multitude of factors that promote unperturbed DNA replication, and protect, repair and restart damaged forks. Here we identify DONSON as a novel fork protection factor, and report biallelic DONSON mutations in 29 individuals with microcephalic dwarfism. We demonstrate that DONSON is a component of the replisome that stabilises forks during normal genome replication. Loss of DONSON leads to severe replication-associated DNA damage arising from nucleolytic cleavage of stalled replication forks. Furthermore, ATR-dependent signalling in response to replication stress is impaired in DONSON-deficient cells, resulting in decreased checkpoint activity, and potentiating chromosomal instability. Hypomorphic mutations substantially reduce DONSON protein levels and impair fork stability in patient cells, consistent with defective DNA replication underlying the disease phenotype. In summary, we identify mutations in DONSON as a common cause of microcephalic dwarfism, and establish DONSON as a critical replication fork protein required for mammalian DNA replication and genome stability.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-12T17:00:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002225","title":"Tracing the origins of relapse in AML to stem cells","description":"In acute myeloid leukemia (AML), most patients relapse despite achieving remission. While relapse-specific mutations are sometimes detected at low frequency within bulk diagnosis samples, the cell type giving rise to relapse is unknown. Through combined genetic and functional analysis of purified subpopulations and xenografts from paired diagnosis/relapse samples, we identified two major patterns of relapse arising from therapy-resistant cells already present at diagnosis. In some cases relapse originated from rare leukemia stem cells with a primitive immunophenotype, while in other instances relapse developed from larger subclones of immunophenotypically-committed cells that retained strong stemness transcriptional signatures. The identification of distinct patterns of relapse should lead to improved methods for disease management and monitoring in AML. Moreover, the shared functional and transcriptional stemness properties that underlie both cellular origins of relapse underscore the importance of developing new therapeutic approaches that target stemness to prevent relapse.","abstract":"In acute myeloid leukemia (AML), most patients relapse despite achieving remission. While relapse-specific mutations are sometimes detected at low frequency within bulk diagnosis samples, the cell type giving rise to relapse is unknown. Through combined genetic and functional analysis of purified subpopulations and xenografts from paired diagnosis/relapse samples, we identified two major patterns of relapse arising from therapy-resistant cells already present at diagnosis. In some cases relapse originated from rare leukemia stem cells with a primitive immunophenotype, while in other instances relapse developed from larger subclones of immunophenotypically-committed cells that retained strong stemness transcriptional signatures. The identification of distinct patterns of relapse should lead to improved methods for disease management and monitoring in AML. Moreover, the shared functional and transcriptional stemness properties that underlie both cellular origins of relapse underscore the importance of developing new therapeutic approaches that target stemness to prevent relapse.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-12T20:26:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002226","title":"Aging and genome-wide patterns of DNA methylation in an African rainforest hunter-gathering population","description":"Aging is associated with widespread changes in genome-wide patterns of DNA methylation. Thousands of CpG sites whose tissue-specific methylation levels are strongly correlated with chronological age have been previously identified. However, the majority of these studies have focused primarily on cosmopolitan populations living in the developed world; it is not known if age-related patterns of DNA methylation at these loci are similar across a broad range of human genetic and ecological diversity. We investigated genome-wide methylation patterns using saliva derived DNA from a traditionally hunting and gathering African populations: the Baka of the western Central African rainforest, together with the ≠Khomani San of the South African Kalahari Desert. We identify hundreds of CpG sites whose methylation levels are significantly associated with age, thousands that are significant in a meta-analysis, and replicate trends previously reported in populations of non-African descent. We confirm that an age associated site in the gene ELOVL2 shows a remarkably congruent relationship with aging in humans, despite extensive genetic and environmental variation across populations. We also demonstrate that genotype state at methylation quantitative trait loci (meQTLs) can affect methylation trends at some known age-associated CpG sites. Our study explores the relationship between CpG methylation and chronological age in populations of African hunter-gatherers, who rely on different diets across diverse ecologies. While many age-related CpG sites replicate across populations, we show that considering common genetic variation at meQTLs further improves our ability to detect previously identified age associations.","abstract":"Aging is associated with widespread changes in genome-wide patterns of DNA methylation. Thousands of CpG sites whose tissue-specific methylation levels are strongly correlated with chronological age have been previously identified. However, the majority of these studies have focused primarily on cosmopolitan populations living in the developed world; it is not known if age-related patterns of DNA methylation at these loci are similar across a broad range of human genetic and ecological diversity. We investigated genome-wide methylation patterns using saliva derived DNA from a traditionally hunting and gathering African populations: the Baka of the western Central African rainforest, together with the ≠Khomani San of the South African Kalahari Desert. We identify hundreds of CpG sites whose methylation levels are significantly associated with age, thousands that are significant in a meta-analysis, and replicate trends previously reported in populations of non-African descent. We confirm that an age associated site in the gene ELOVL2 shows a remarkably congruent relationship with aging in humans, despite extensive genetic and environmental variation across populations. We also demonstrate that genotype state at methylation quantitative trait loci (meQTLs) can affect methylation trends at some known age-associated CpG sites. Our study explores the relationship between CpG methylation and chronological age in populations of African hunter-gatherers, who rely on different diets across diverse ecologies. While many age-related CpG sites replicate across populations, we show that considering common genetic variation at meQTLs further improves our ability to detect previously identified age associations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-13T07:23:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002227","title":"One breast patient panel of heterogenetic genomes reveals genetic alterations driving ductal carcinoma in situ progression into invasive lesions","description":"Recent progress in addressing a fine cancer genomic landscape of human breast cancers has led to a promising translational platform based on which precision strategies could be feasibly proposed on the clinical side after connecting to certain annotated genetic alterations on cancer genomes. However, to a specific field, time-series clinical and genetic data of one patient need to be fed into study therefore the potential causal connection could be evidenced on molecular level. In this study, we performed whole exome analysis on a panel of samples from one rare patient who had both independent dcis and idc lesions on her left breast. This panel indeed provides us a precious opportunity of precisely shooting few genetic variances evolutionarily drove invasion of cancer cells, and consequently lead to a bad prognosis. In this case, at first we identified that VEGF pathway were genetically disturbed in dcis sample. Interestingly, in idc sample, four more genes in such pathway were observed being mutated, in which mutated ACTN2 were found in seven samples in TCGA breast patients. We report here that those patients with somatically mutated ACTN2 are statistically with shorted Overall survival time (p &lt; 0.05), evidencing that (1) driver gene was identified and (2) one patient panel provides a sharpen tool of genetically providing explanations for cancer development.","abstract":"Recent progress in addressing a fine cancer genomic landscape of human breast cancers has led to a promising translational platform based on which precision strategies could be feasibly proposed on the clinical side after connecting to certain annotated genetic alterations on cancer genomes. However, to a specific field, time-series clinical and genetic data of one patient need to be fed into study therefore the potential causal connection could be evidenced on molecular level. In this study, we performed whole exome analysis on a panel of samples from one rare patient who had both independent dcis and idc lesions on her left breast. This panel indeed provides us a precious opportunity of precisely shooting few genetic variances evolutionarily drove invasion of cancer cells, and consequently lead to a bad prognosis. In this case, at first we identified that VEGF pathway were genetically disturbed in dcis sample. Interestingly, in idc sample, four more genes in such pathway were observed being mutated, in which mutated ACTN2 were found in seven samples in TCGA breast patients. We report here that those patients with somatically mutated ACTN2 are statistically with shorted Overall survival time (p &lt; 0.05), evidencing that (1) driver gene was identified and (2) one patient panel provides a sharpen tool of genetically providing explanations for cancer development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002228","title":"Identification of fungal species in brain tissue from Alzheimer's disease","description":"Identification of fungal species present in the central nervous system  tissue from Alzheimer's disease patients by next-generation sequencing.","abstract":"Identification of fungal species present in the central nervous system  tissue from Alzheimer's disease patients by next-generation sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-16T09:59:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002229","title":"SCAN_B_Population_Breast_Cancer_Study","description":"Characterization of tumor genome signatures that correlate with homologous recombination DNA repair deficiency (HRD) and BRCA1 and BRCA2 gene alterations. Description of the frequency of HRD in a population-based consecutive series of breast cancer, initially focusing on triple (ER, PgR, HER2) negative tumors.","abstract":"Characterization of tumor genome signatures that correlate with homologous recombination DNA repair deficiency (HRD) and BRCA1 and BRCA2 gene alterations. Description of the frequency of HRD in a population-based consecutive series of breast cancer, initially focusing on triple (ER, PgR, HER2) negative tumors.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002230","title":"Whole genome bisulfite sequencing of hepatitis B virus-associated hepatocellular carcinoma tumor and non-cancerous samples","description":"To understand comprehensive epigenetic alterations in hepatitis B virus-associated HCC, we have conducted a whole genome bisulfite sequencing of 5 tumor samples and 3 non-cancerous samples (3 pairs and 2 tumors).","abstract":"To understand comprehensive epigenetic alterations in hepatitis B virus-associated HCC, we have conducted a whole genome bisulfite sequencing of 5 tumor samples and 3 non-cancerous samples (3 pairs and 2 tumors).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-17T07:52:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002231","title":"Sequencing of ovarian cancer patient derived cell lines (temporar study for Julia Neugebauer)","description":"Whole genome sequencing of ovarian cancer patient derived cell lines to determine patient-specific genetic abberations and to link drug responses to genotypes.","abstract":"Whole genome sequencing of ovarian cancer patient derived cell lines to determine patient-specific genetic abberations and to link drug responses to genotypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002232","title":"RNAseq___The_transcriptional_consequences_of_aneuploid_and_polyploid_hepatocytes_in_human","description":"To study the transcriptional consequences of aneuploid and polyploid hepatocytes in human","abstract":"To study the transcriptional consequences of aneuploid and polyploid hepatocytes in normal and diseased human liver","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002233","title":"WGS___The_transcriptional_consequences_of_aneuploid_and_polyploid_hepatocytes_in_human","description":"To study the transcriptional consequences of aneuploid and polyploid hepatocytes in human","abstract":"To study the transcriptional consequences of aneuploid and polyploid hepatocytes in normal and diseased human liver","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002234","title":"Global Anaplastic Thyroid Cancer Initiative","description":"Thyroid cancer is the most common endocrine malignancy. Most thyroid cancers are of the well-differentiated (non-aggressive) phenotype, and are almost always cured with standard treatments. In contrast, anaplastic thyroid cancer (ATC) is rare, accounting for only 1% of thyroid cancers, however it is perhaps the most lethal human malignancy with an average survival of 3 to 6 months. ATC presents with dramatic and rapid onset of airway and esophageal blockage with frequent spread to the lungs. Interestingly, 21–79% of ATCs have coexisting areas or a previous history of well-differentiated cancers. Although this suggests a progression from well-differentiated cancers to ATC, to date there is little molecular conformation that such a progression exists versus de novo generation of ATC. As ATC is extremely rare and most cases are inoperable, there are a paucity of tissue samples for study at any one center. The Global Anaplastic Thyroid Cancer Initiative (GATCI) aims to unite international institutions in order to pool samples (ATC with or without a paired well-differentiated component) for a comprehensive analysis of the genomic landscape of this disease.","abstract":"Thyroid cancer is the most common endocrine malignancy. Most thyroid cancers are of the well-differentiated (non-aggressive) phenotype, and are almost always cured with standard treatments. In contrast, anaplastic thyroid cancer (ATC) is rare, accounting for only 1% of thyroid cancers, however it is perhaps the most lethal human malignancy with an average survival of 3 to 6 months. ATC presents with dramatic and rapid onset of airway and esophageal blockage with frequent spread to the lungs. Interestingly, 21–79% of ATCs have coexisting areas or a previous history of well-differentiated cancers. Although this suggests a progression from well-differentiated cancers to ATC, to date there is little molecular conformation that such a progression exists versus de novo generation of ATC. As ATC is extremely rare and most cases are inoperable, there are a paucity of tissue samples for study at any one center. The Global Anaplastic Thyroid Cancer Initiative (GATCI) aims to unite international institutions in order to pool samples (ATC with or without a paired well-differentiated component) for a comprehensive analysis of the genomic landscape of this disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-17T20:21:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002235","title":"Assessment of OICR Analysis Pipelines using the DREAM-Somatic Mutation Challenge","description":"The OICR analysis pipelines were assessed using the DREAM Somatic Mutation Challenge.  Non-synthetic data, provided by the Dream Challenge, were aligned using BWA, BWA-MEM and Novoalign.  Somatic variants were then called using our Mutect/Strelka pipeline.  Synthetic data was back-extracted from supplied aligned bam files, then realigned using the same aligners, followed by running through the same somatic calling pipeline.  Results were uploaded the DREAM-SMC site and scored against other submissions.","abstract":"The OICR analysis pipelines were assessed using the DREAM Somatic Mutation Challenge.  Non-synthetic data, provided by the Dream Challenge, were aligned using BWA, BWA-MEM and Novoalign.  Somatic variants were then called using our Mutect/Strelka pipeline.  Synthetic data was back-extracted from supplied aligned bam files, then realigned using the same aligners, followed by running through the same somatic calling pipeline.  Results were uploaded the DREAM-SMC site and scored against other submissions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002236","title":"Genetics_of_gene_expression_in_human_macrophage_response_to_Salmonella","description":"This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Understanding how cells sense and respond to their environment, and how these responses are modulated by genetic variation, are fundamental biological problems, particularly for understanding how pathogenic organisms invade and manipulate the cells of the human immune system. Macrophages recognize and respond to many important human pathogens including HIV-1, Mycobacteria tuberculosis and Salmonella. This study will focus on the cellular response of human macrophages to Salmonella infection and how this response is modulated by the genetic bacground of the individual as well as additional pro-inflammatory stimulus (interferon-gamma priming).\n\nWe will acquire 100 human induced pluripotent stem cell lines from the HipSci project, differentiate the cells in vitro into macrophages and expose them to four environmental conditions: (i) no stimulation, (ii) interferon-gamma (18h),  (iii) Salmonella typhimurium SL1344 (5h),  (iv) interferon-gamma (18h) + Salmonella (5h).Subsequently, we will isolate RNA from the samples for sequencing.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-18T14:51:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002237","title":"Sequencing of liver cancer cell lines","description":"Liver cancer is a dreadful disease with limited therapeutic options. How to translate genomic findings into biomarkers and precision treatment is challenging. A large cell line-based platform was established, termed as Liver Cancer Model Repository. Heterogeneities in patients were faithfully recapitulated by 81 liver cancer cell lines at genomic and transcriptomic levels. This platform provides a rich resource and models to study cancer drivers and drug responses in liver cancer.","abstract":"Liver cancer is a dreadful disease with limited therapeutic options. How to translate genomic findings into biomarkers and precision treatment is challenging. A large cell line-based platform was established, termed as Liver Cancer Model Repository. Heterogeneities in patients were faithfully recapitulated by 81 liver cancer cell lines at genomic and transcriptomic levels. This platform provides a rich resource and models to study cancer drivers and drug responses in liver cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-19T07:27:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002238","title":"IBD_Whole_Genome_Sequencing","description":"We will sequence at 15X coverage the genomes of 1536 IBD patients. These samples are currently onsite at Sanger and made available for sequencing via our collaboration with the UK IBD Genetics consortium. \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Whole genome sequences at 15X depth of patients with Inflammatory Bowel Disease","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-19T12:14:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002239","title":"Drug screening and whole genome sequencing of primary cells and cell lines from ovarian cancer patients to associate genomic aberrations with in vitro drug sensitivities","description":"Identifying drugs for cancers with poor prognosis like ovarian cancer (OC) is hindered by inappropriate cell models and the limitations of current viability assays. We developed an automated confocal microscopy-based live cell assay (DeathPro) that robustly de-convolves cell death and proliferation over time by employing a specific image processing strategy. Using DeathPro, we screened nine OC patient-derived cell lines and one normal cell line (HOSEpiC) with 22 drugs or combinations. Whole genome was performed to analyze if the cell lines harbor OC-typical genomic aberrations and to relate genomic features to drug sensitivities. Commonly observed alterations in OC patients like TP53 mutations and MYC or PI3KCA amplifications were absent in the normal cell line but frequently detected in the OC cell lines. Moreover, genome-derived homologous recombination deficiency (HRD) scores of the OC cell lines correlated with their responses to carboplatin, olaparib and DNA demethylation drugs. Overall, we propose an imaging-based platform to guide drug development and genome-drug sensitivity analysis.","abstract":"Identifying drugs for cancers with poor prognosis like ovarian cancer (OC) is hindered by inappropriate cell models and the limitations of current viability assays. We developed an automated confocal microscopy-based live cell assay (DeathPro) that robustly de-convolves cell death and proliferation over time by employing a specific image processing strategy. Using DeathPro, we screened nine OC patient-derived cell lines and one normal cell line (HOSEpiC) with 22 drugs or combinations. Whole genome was performed to analyze if the cell lines harbor OC-typical genomic aberrations and to relate genomic features to drug sensitivities. Commonly observed alterations in OC patients like TP53 mutations and MYC or PI3KCA amplifications were absent in the normal cell line but frequently detected in the OC cell lines. Moreover, genome-derived homologous recombination deficiency (HRD) scores of the OC cell lines correlated with their responses to carboplatin, olaparib and DNA demethylation drugs. Overall, we propose an imaging-based platform to guide drug development and genome-drug sensitivity analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-20T09:14:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002240","title":"Osteosarcoma_WGBS","description":"This is a continuation of the osteosarcoma work we have undertaken, with WGBS.","abstract":"This is a continuation of the osteosarcoma work we have undertaken, with WGBS.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002244","title":"Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis","description":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","abstract":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002245","title":"Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis","description":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","abstract":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002246","title":"Indonesian sea-nomads genomic history","description":"This study observes the origin of the last living sea nomad group in Indonesia using genome-wide SNP data, and tracks their dispersal in the archipelago. This study involves new samples on not only the sea nomad group, but also surrounding populations where the sea nomad settled. We revealed the scenario of their origin and unique admixture patterns during their dispersal and re-settlement.","abstract":"This study observes the origin of the last living sea nomad group in Indonesia using genome-wide SNP data, and tracks their dispersal in the archipelago. This study involves new samples on not only the sea nomad group, but also surrounding populations where the sea nomad settled. We revealed the scenario of their origin and unique admixture patterns during their dispersal and re-settlement.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-26T13:23:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002247","title":"TRACERx 100: whole exome data of the first 100 TRACERx tumours","description":"BACKGROUNDTRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC). METHODSMultiregion high-depth whole-exome sequencing (M-seq) was performed on 100 early stage NSCLC tumors resected prior to systemic therapy. A total of 327 tumor regions were sequenced and analyzed to define evolutionary histories, obtain a census of clonal and subclonal events, and assess the relationship between ITH and recurrence-free survival (RFS).  RESULTSWidespread ITH was observed for both somatic copy number alterations (median 48% [0.03-88%]) and mutations (median 30% [0.5-93%]). Driver mutations in EGFR, MET, BRAF and TP53 were almost always clonal. However, heterogeneous driver alterations occurring later in evolution were found in over 75% of tumors and were common in PIK3CA, NF1 and genes involved in chromatin modification and DNA response and repair. Genome doubling and ongoing dynamic chromosomal instability (CIN), illustrated by mirrored subclonal allelic imbalance, were identified as causes of ITH resulting in parallel evolution of driver copy number events, including amplifications of CDK4, FOXA1, and BCL11A. Elevated copy number heterogeneity was associated with shorter RFS (HR=4.9, P=0.00044), which remained significant in a multivariate analysis.CONCLUSIONSITH mediated through CIN, rather than point mutational heterogeneity, was associated with increased risk of relapse, supporting its value as a prognostic predictor, and the need to target this high-risk phenotype.","abstract":"BACKGROUNDTRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC). METHODSMultiregion high-depth whole-exome sequencing (M-seq) was performed on 100 early stage NSCLC tumors resected prior to systemic therapy. A total of 327 tumor regions were sequenced and analyzed to define evolutionary histories, obtain a census of clonal and subclonal events, and assess the relationship between ITH and recurrence-free survival (RFS).  RESULTSWidespread ITH was observed for both somatic copy number alterations (median 48% [0.03-88%]) and mutations (median 30% [0.5-93%]). Driver mutations in EGFR, MET, BRAF and TP53 were almost always clonal. However, heterogeneous driver alterations occurring later in evolution were found in over 75% of tumors and were common in PIK3CA, NF1 and genes involved in chromatin modification and DNA response and repair. Genome doubling and ongoing dynamic chromosomal instability (CIN), illustrated by mirrored subclonal allelic imbalance, were identified as causes of ITH resulting in parallel evolution of driver copy number events, including amplifications of CDK4, FOXA1, and BCL11A. Elevated copy number heterogeneity was associated with shorter RFS (HR=4.9, P=0.00044), which remained significant in a multivariate analysis.CONCLUSIONSITH mediated through CIN, rather than point mutational heterogeneity, was associated with increased risk of relapse, supporting its value as a prognostic predictor, and the need to target this high-risk phenotype.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-30T13:07:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002248","title":"Genome-wide DNA methylation profiles by MeDIP-seq of cord blood cells and cord blood mononuclear cells obtained from twins conceived through in vitro fertilization and naturally conceived controls","description":"The study included 47 newborn twins conceived though in vitro fertilisation (IVF) and 60 non-IVF-conceived twins from the Peri/postnatal Epigenetic Twins Study (PETS). Cord blood was collected at birth and used to process mononuclear cells. Whole blood cells (WBCs) from cord blood of 98 twins (40 IVF and 58 non-IVF) and cord blood mononuclear cells (CBMCs) of 82 twins (35 IVF and 47 non-IVF) were subjected to DNA methylation profiling. Methylated DNA immunoprecipitation followed by deep sequencing (MeDIP-seq) was applied to generate genome-wide DNA methylation profiles in a total of 180 samples. Single-end reads were mapped onto hg19 using BWA. Methylation levels were quantified using MEDIPS and used to identify IVF-associated differentially methylated regions.","abstract":"The study included 47 newborn twins conceived though in vitro fertilisation (IVF) and 60 non-IVF-conceived twins from the Peri/postnatal Epigenetic Twins Study (PETS). Cord blood was collected at birth and used to process mononuclear cells. Whole blood cells (WBCs) from cord blood of 98 twins (40 IVF and 58 non-IVF) and cord blood mononuclear cells (CBMCs) of 82 twins (35 IVF and 47 non-IVF) were subjected to DNA methylation profiling. Methylated DNA immunoprecipitation followed by deep sequencing (MeDIP-seq) was applied to generate genome-wide DNA methylation profiles in a total of 180 samples. Single-end reads were mapped onto hg19 using BWA. Methylation levels were quantified using MEDIPS and used to identify IVF-associated differentially methylated regions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-30T13:43:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002249","title":"Illumina Omni5 SNP chip genotyping of MacTel cases and unaffected controls for a genome-wide association study","description":"Macular telangiectasia type 2 (MacTel) is a rare neurovascular degenerative retinal disease. To identify genetic susceptibility loci for MacTel, we performed a genome-wide association study (GWAS). We genotyped 704 samples, of which 678 have consented to be available here. These samples mainly include MacTel cases but also some unaffected controls (often spouses). The samples were collected through the MacTel Project (funded by the Lowy Medical Research Institute), which includes a registry and extensive clinical analysis to confirm the presence of MacTel in affected individuals. Additional controls were obtained from dbGap [phs000429.v1.p1]. After QC steps, the GWAS utilised 476 cases and 1733 controls of European ancestry.","abstract":"Macular telangiectasia type 2 (MacTel) is a rare neurovascular degenerative retinal disease. To identify genetic susceptibility loci for MacTel, we performed a genome-wide association study (GWAS). We genotyped 704 samples, of which 678 have consented to be available here. These samples mainly include MacTel cases but also some unaffected controls (often spouses). The samples were collected through the MacTel Project (funded by the Lowy Medical Research Institute), which includes a registry and extensive clinical analysis to confirm the presence of MacTel in affected individuals. Additional controls were obtained from dbGap [phs000429.v1.p1]. After QC steps, the GWAS utilised 476 cases and 1733 controls of European ancestry.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-30T14:32:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002250","title":"FPLD1_GWAS_Replication","description":"FPLD1 or familial partial lipodystrophy type 1 is a rare disorder of fat distribution associated with severe insulin resistance and with an extreme phenotype that mimics that of the more commonly found metabolic syndrome. Our earlier WES studies suggest that at least in some cases the disorder is not likely to be a single gene defect but could be somewhat more complex.                                                                                                                                            We have previously genotyped 45 individuals from the UK on the Illumina core-exome array, using the data for two purposes.  Firstly to calculate a \"metabolic syndrome\" genetic risk score (identified by collaborators based on GWAS data for fasting insulin, lipid levels, blood pressure, BMI, WHR and other more sophisticated measures of fat distribution), to test whether these patients happened to lie at the top end of this risk score.  Secondly, we compared the samples with existing female UKHLS controls to attempt to identify new loci associated with this disease.                                                                                                                                               We would like to repeat this experiment using a further ~150 Spanish individuals (also genotyped on the Illumina core-exome array) and meta-analyse the results with the previous data from the UK. \n This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"FPLD1 or familial partial lipodystrophy type 1 is a rare disorder of fat distribution associated with severe insulin resistance and with an extreme phenotype that mimics that of the more commonly found metabolic syndrome. Our earlier WES studies suggest that at least in some cases the disorder is not likely to be a single gene defect but could be somewhat more complex. DNA samples from ~150 Spanish FPLD1 cases and controls will be used to run a GWAS to look for variants associated with FPLD1 and to calculate genetic risk scores. We will also meta-analyse with previous data from the UK.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002251","title":"This study explored and validated the clinical application of targeted NGS of circulating tumor DNA in identifying tumor-specific mutations and uncovering clinical actionable targets in a variety of solid tumors in large patient cohorts.","description":"Cancer is a disease of genetic alterations. Comprehensive genetic diagnosis is needed to match each patient to appropriate cancer therapy. However, acquisition of representative tumor samples is invasive and often infeasible. Circulating tumor DNA (ctDNA) is a promising non-invasive biomarker for cancer mutational profiling. Here we implemented targeted next generation sequencing (NGS) with a customized pan-cancer gene panel on 605 clinical ctDNA samples in multiple cancer types. Overall, tumor-specific mutations were identified in 87% of ctDNA samples, with mutation spectra highly concordant with their matched tumor tissues. 71% of patients have at least one clinical actionable mutation with 76% of which have suggested drugs approved or in clinical trials. In particular, our study reveals a unique mutation spectrum in Chinese lung cancer patients, which could be used to guide treatment decision and monitor the appearance of drug-resistant mutations. Taken together, our study demonstrated the clinical utility of target NGS-based ctDNA mutational profiling to guide cancer treatment decision.","abstract":"Cancer is a disease of genetic alterations. Comprehensive genetic diagnosis is needed to match each patient to appropriate cancer therapy. However, acquisition of representative tumor samples is invasive and often infeasible. Circulating tumor DNA (ctDNA) is a promising non-invasive biomarker for cancer mutational profiling. Here we implemented targeted next generation sequencing (NGS) with a customized pan-cancer gene panel on 605 clinical ctDNA samples in multiple cancer types. Overall, tumor-specific mutations were identified in 87% of ctDNA samples, with mutation spectra highly concordant with their matched tumor tissues. 71% of patients have at least one clinical actionable mutation with 76% of which have suggested drugs approved or in clinical trials. In particular, our study reveals a unique mutation spectrum in Chinese lung cancer patients, which could be used to guide treatment decision and monitor the appearance of drug-resistant mutations. Taken together, our study demonstrated the clinical utility of target NGS-based ctDNA mutational profiling to guide cancer treatment decision.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-30T19:27:18+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002252","title":"Mechanisms_of_rearrangement_signatures","description":"The aims of the study is to:\n\n1. To map double strand breaks introduced genome-wide and to monitor their repair, leading to mechanistic insights into the repair process and the genetic control of discrete steps. \n2. To understand how cell coordinates the activities of multiple DNA repair pathways that respond to DNA DSBs and how the relative importance of these different systems is modulated during cell cycle transition/ and in different cells (i.e. BRCA mutants vs. BRCA normal; cancer vs. normal). \n3. To understand the cellular and molecular requirements that govern the genesis of genomic rearrangements.","abstract":"Recent studies from the group have revealed that a single gene defect does not simply produce a single mutational signature. For example, we now know that BRCA1 nullness consistently presents not one, but at least six distinctive mutational signatures including two base substitution signatures, one indel pattern, three rearrangement signatures and distinct copy number profiles (Morganella et al., 2016; Nik-Zainal et al., 2016). This plethora of mutational signatures are likely representative of the multitude of compensatory recombination repair and translesion repair pathways that are called into action in the face of defective BRCA1, which is involved in homologous recombination (HR) pathway. Furthermore, these six signatures exhibit distinctive behaviours across replication time domains. \nThe aim of the project is to dissect the mechanisms that contribute towards double strand break repair (DSBR), and to understand how these rearrangement signatures arise.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002253","title":"Genetic_vulnerability_of_knockout_cancer_lines","description":"Genome-wide CRISPR/Cas9 library screen was performed in isogenic cell lines. Three biological replicates were used. Cells were harvested at initiation of screen and at specific time points following cell culture. Using this approach we aim to identify genes specifically important in cell survival in engineered cell lines. Please perform 72, instead of 36, PCR reactions as the screen performed at 200x coverage.","abstract":"Genome-wide CRISPR/Cas9 library screen was performed in isogenic cell lines. Three biological replicates were used. Cells were harvested at initiation of screen and at specific time points following cell culture. Using this approach we aim to identify genes specifically important in cell survival in engineered cell lines. Please perform 72, instead of 36, PCR reactions as the screen performed at 200x coverage.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-31T14:19:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002254","title":"KOTau1_mouse","description":"This study contains parallel cDNA and gDNA libraries from 96 single cell neurons derived from KOTau1 mouse. Libraries are prepared with modified G&amp;T method from frozen tissue. All the cDNA libraries are pooled and has Nextera-index Set A. The gDNA libraries are also pooled and had Nextera-index SetB. To sum up there are two libraries to be pooled and sequenced on one lane of Hiseq 4000.","abstract":"This study is part of  eu-jpnd-tv project (project ID: G2089), which aim to study the role of neuronal genomic instability in the pathogenesis of Alzheimer's disease. This particular study will use KOTau1 mouse, as a preliminary study to make sure that our novel method able to extract gDNA and cDNA from frozen single neurons and produce quality sequence data. Moreover, this study will inform us about role of Tau in genome instability in neurodegenerative disorders. \nProject outlines with regards to CGP informatics support\nFor this project requires sequence aligment and QC. Following by single cell CNV analysis for gDNA and single cell RNA analysis","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002255","title":"Functional_genomics_approaches_to_understand_osteoarthritis","description":"The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of large joint (hip and knee) osteoarthritis which culminates in the need for total joint replacement (TJR). We will obtain diseased and non-diseased cartilage as well as other disease-relevant tissue following TJR, coupled with a blood sample. We will generate genotype data and will characterise the pairs of diseased and non-diseased tissue samples in terms of methylation, transcription (RNASeq) and expression (quantitative proteomics).  We will apply integrative approaches to combine information across the –omics levels to characterise genes, pathways, and networks that underlie osteoarthritis progression.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of large joint (hip and knee) osteoarthritis which culminates in the need for total joint replacement (TJR). We will obtain diseased and non-diseased cartilage as well as other disease-relevant tissue following TJR, coupled with a blood sample. We will generate genotype data and will characterise the pairs of diseased and non-diseased tissue samples in terms of methylation, transcription (RNASeq) and expression (quantitative proteomics).  We will apply integrative approaches to combine information across the –omics levels to characterise genes, pathways, and networks that underlie osteoarthritis progression.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-01-31T15:52:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002256","title":"A Functional Network of Gastric-Cancer-Associated Splicing Events Controlled by Dysregulated Splicing Factors","description":"Except for a few genes known to have oncogenic spliceforms in gastric cancer, the full scope of aberrant splicing in gastric oncogenesis remains unclear. In this study, we elucidated the alternative splicing events associated with gastric carcinogenesis and identified upstream regulators governing these events. We performed RNA-seq on 19 matched tumor/normal pairs and a panel of gastric cancer cell lines, and identified 361 tumor associated (TA) alternative splicing events (ASEs), which included known oncogenic ASEs in genes such as INSR, FGFR2, CD44 and KRAS. We further identified 8 splicing factors dysregulated in gastric tumors, the expression of which are correlated to the splice ratio of the TA ASEs. We thereby constructed a dysregulated splicing network in gastric cancer, consisting of alternative splicing changes correlated to their potential regulators. This network featured three potential regulatory modules centered around the splicing factors ESRP2, MBNL1 and PTPB1. Knockdown of each splicing factor led to the expected changes in splicing of approximately half of the ASEs assayed. Thus, dysregulation of the splicing factors indeed was the cause of many of the TA ASEs. Pathway enrichment analysis showed that genes affected by tumor associated splicing were pre-dominantly involved in cytoskeletal organization. Concordant with this, knockdown of the splicing factors regulating the TA ASEs led to the expected changes in trans-well migration activity. Thus, we have established for the first time a comprehensive splicing network that likely drives gastric tumor progression, based on which novel therapeutic targets can be identified for further evaluation.","abstract":"Except for a few genes known to have oncogenic spliceforms in gastric cancer, the full scope of aberrant splicing in gastric oncogenesis remains unclear. In this study, we elucidated the alternative splicing events associated with gastric carcinogenesis and identified upstream regulators governing these events. We performed RNA-seq on 19 matched tumor/normal pairs and a panel of gastric cancer cell lines, and identified 361 tumor associated (TA) alternative splicing events (ASEs), which included known oncogenic ASEs in genes such as INSR, FGFR2, CD44 and KRAS. We further identified 8 splicing factors dysregulated in gastric tumors, the expression of which are correlated to the splice ratio of the TA ASEs. We thereby constructed a dysregulated splicing network in gastric cancer, consisting of alternative splicing changes correlated to their potential regulators. This network featured three potential regulatory modules centered around the splicing factors ESRP2, MBNL1 and PTPB1. Knockdown of each splicing factor led to the expected changes in splicing of approximately half of the ASEs assayed. Thus, dysregulation of the splicing factors indeed was the cause of many of the TA ASEs. Pathway enrichment analysis showed that genes affected by tumor associated splicing were pre-dominantly involved in cytoskeletal organization. Concordant with this, knockdown of the splicing factors regulating the TA ASEs led to the expected changes in trans-well migration activity. Thus, we have established for the first time a comprehensive splicing network that likely drives gastric tumor progression, based on which novel therapeutic targets can be identified for further evaluation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-01T02:17:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002257","title":"The_Causes_of_Clonal_Blood_Cell_Disorders_Study___SCOR_Custom","description":"We took a bone marrow aspirate and peripheral blood samples from a healthy patient aged around 60, and use flow cytometry to isolate 100 HSCs, 50 MEPs, and 50 GMPs. We grew these up into colonies, then whole genome sequenced each colony. Somatic mutations act as a unique barcode for each clone. We have designed a panel for targeted resequencing of the mutations that we find. We are now looking for these mutations in the peripheral blood, to see the dynamics of how HSCs contribute to the peripheral blood in health.","abstract":"We took a bone marrow aspirate and peripheral blood samples from a healthy patient aged around 60, and use flow cytometry to isolate 100 HSCs, 50 MEPs, and 50 GMPs. We grew these up into colonies, then whole genome sequenced each colony. Somatic mutations act as a unique barcode for each clone. We have designed a panel for targeted resequencing of the mutations that we find. We are now looking for these mutations in the peripheral blood, to see the dynamics of how HSCs contribute to the peripheral blood in health.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-01T09:28:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002258","title":"Exome Sequencing Analysis of Familial Non-Medullary thyroid Cancer (FNMTC)","description":"The goal of this project was to identify novel genes associated with thyroid cancer risk. Thyroid cancer risk increases with diagnosis in first-degree relatives with variable penetrance. While some polymorphisms are reported to increase low-penetrance thyroid cancer risk, the genetic etiology of low- and high-penetrance thyroid cancer is not well understood.","abstract":"The goal of this project was to identify novel genes associated with thyroid cancer risk. Thyroid cancer risk increases with diagnosis in first-degree relatives with variable penetrance. While some polymorphisms are reported to increase low-penetrance thyroid cancer risk, the genetic etiology of low- and high-penetrance thyroid cancer is not well understood.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002259","title":"The_impact_of_the_human_leukaemia_virus_HTLV_1_on_host_gene_expression","description":"PBMCs were purified from blood samples of 8 HTLV-1 infected individuals, and cryo-preserved in fetal calf serum  containing 10% DMSO. DNA from each samples was extracted using Qiagen Blood &amp; Tissue kit according to the manufacturer's protocol. \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"The study is designed to test the hypothesis that the human leukaemia virus HTLV-1 alters the structure and expression selectively in the chromosome in which the provirus is integrated.  The project involves whole-genome sequencing of DNA extracted from PBMCs of 8 HTLV-1 infected individuals.  The resulting data will be used to distinguish the chromosome carrying the provirus from the homologous, unaltered chromosome.  The sequencing data will then be analysed in concert with gene expression and chromatin structure studies at the single clone level.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-02T10:36:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002260","title":"Statin_induced_expression_differences_in_iPSC_derived_hepatocyte_like_cells_and_primary_hepatocytes_RNAseq","description":"Statins are used World-wide to lower blood cholesterol levels by inhibition of Hydroxymethylglutaryl CoA Reductase in the liver, with pleiotropic effects. In this experiment we investigate the differences in gene expression before and after exposing both human iPSC derived hepatocyte-like cells and primary hepatocytes to Simvastatin at varying doses (0, 0.2, 2 and 5uM Simvastatin).\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Statins are used World-wide to lower blood cholesterol levels by inhibition of Hydroxymethylglutaryl CoA Reductase in the liver, with pleiotropic effects. In this experiment we investigate the differences in gene expression before and after exposing both human iPSC derived hepatocyte-like cells and primary hepatocytes to Simvastatin at varying doses (0, 0.2, 2 and 5uM Simvastatin).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002261","title":"CELM","description":"This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Haematological cancers occurs due to genetic changes that typically accumulate over many years. Recent work has shown that some individuals harbour leukaemia-associated gene mutations in some of their blood cells, and are at higher risk of developing blood cancers. The presence of leukaemia-associated mutations in the blood of healthy people is called ‘clonal haemopoiesis of indeterminate significance’, or CHIP. This study will investigate the natural history of CHIP over time and risk factors for progression to malignancy.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-02T12:50:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002262","title":"TSG_knock_out_in_hiPSCs","description":"We will perform RNAseq to evaluate the effects of the loss of a list of TSGs on the transcriptome.","abstract":"Tumor suppressor genes account for the majority of cancer drivers but they are rarely exploited therapeutically. Therefore we aim to better understand the effects of their loss to identify potential novel therapies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-02T13:31:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002263","title":"Australian whole-genome sequences for the Pan Prostate Study","description":"The Pan Prostate project is an international consortium dedicated to bringing together all prostate cancer whole-genome sequencing projects. All samples will be processed using a unified pipeline giving rise to the largest prostate cancer whole-genome collection. This study is specific for all samples coming from Australia.","abstract":"The Pan Prostate project is an international consortium dedicated to bringing together all prostate cancer whole-genome sequencing projects. All samples will be processed using a unified pipeline giving rise to the largest prostate cancer whole-genome collection. This study is specific for all samples coming from Australia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002264","title":"Study title","description":"Study abstract","abstract":"Study abstract","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002265","title":"Regions of common inter-individual DNA methylation differences in human monocytes.","description":"Based on whole genome bisulfite sequencing of five human monocytes from unrelated individuals, we have identified regions of common inter-individual DNA methylation differences, where methylation is inversely correlated with active histone marks, but not with the expression of the associated genes. Genome-wide association studies in 1128 individuals show that allelic DNA methylation is caused by genetic variation in cis. At some loci, DNA methylation appears to be affected also by genetic variation in trans.","abstract":"Based on whole genome bisulfite sequencing of five human monocytes from unrelated individuals, we have identified regions of common inter-individual DNA methylation differences, where methylation is inversely correlated with active histone marks, but not with the expression of the associated genes. Genome-wide association studies in 1128 individuals show that allelic DNA methylation is caused by genetic variation in cis. At some loci, DNA methylation appears to be affected also by genetic variation in trans.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-03T14:09:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002266","title":"NeuroChip genotyping data of neurological normal controls","description":"For the pilot NeuroChip data, we genotyped a cohort of 273 neurologically normal controls as per the manufacturer's instructions (Illumina). These samples have been collected by the North American Brain Expression Consortium (NABEC). In total, 183 males and 90 females were included. All subjects reported European ancestry and had no neurological disease based on pathological evaluation. All samples were obtained from North American brain banks.","abstract":"For the pilot NeuroChip data, we genotyped a cohort of 273 neurologically normal controls as per the manufacturer's instructions (Illumina). These samples have been collected by the North American Brain Expression Consortium (NABEC). In total, 183 males and 90 females were included. All subjects reported European ancestry and had no neurological disease based on pathological evaluation. All samples were obtained from North American brain banks.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002267","title":"Accurate genomic variant characterisation and phasing information calling from whole genome sequencing of picogram quantities of DNA","description":"Minimal residual disease (MRD) following cancer therapy predisposes to recurrence. Genome analysis of MRD could therefore give insights into evolutionary mechanisms that might govern this phenomenon [27492892]. However, to-date, this has largely been restricted to studies utilizing targeted sequencing [26311728, 27384348] of known somatic mutations due to the challenges of sampling residual cells and whole genome sequencing of sub-nanogram quantities of DNA. Whole genome sequencing of sub-nanogram quantities, although possible, is inherently confounded by genomic amplification bias. A previous report suggested that accurate whole genome sequencing is possible from as little as 10 to 20 cells with the added advantage of obtaining reconstructed long fragment reads and, therefore, phase information [22785314]. However, the ability of this technique to estimate accurate variant allele fractions (VAFs) to enable the identification of somatic chromosomal numeric aberrations (SCNAs) in tumours remains to be determined. In addition, the platform that was used to generate such data is no longer available for general use. Here we implemented a modified protocol to generate synthetic long fragment read whole genome sequencing data using Illumina sequencing technology. Our method differs from the pre-existing TruSeq/Moleculo sequencing approach [24561555] in that it is based on compartmentalization of picogram quantities of starting DNA material (Figure 1A). Barcoding of individual wells enables obtaining a digital count of the number of wells that contained any particular allele. We hypothesized that this digital analysis of picogram quantities of DNA (DigiPico), would yield an accurate estimate of VAFs and, therefore, accurate calling of SCNAs.","abstract":"Minimal residual disease (MRD) following cancer therapy predisposes to recurrence. Genome analysis of MRD could therefore give insights into evolutionary mechanisms that might govern this phenomenon [27492892]. However, to-date, this has largely been restricted to studies utilizing targeted sequencing [26311728, 27384348] of known somatic mutations due to the challenges of sampling residual cells and whole genome sequencing of sub-nanogram quantities of DNA. Whole genome sequencing of sub-nanogram quantities, although possible, is inherently confounded by genomic amplification bias. A previous report suggested that accurate whole genome sequencing is possible from as little as 10 to 20 cells with the added advantage of obtaining reconstructed long fragment reads and, therefore, phase information [22785314]. However, the ability of this technique to estimate accurate variant allele fractions (VAFs) to enable the identification of somatic chromosomal numeric aberrations (SCNAs) in tumours remains to be determined. In addition, the platform that was used to generate such data is no longer available for general use. Here we implemented a modified protocol to generate synthetic long fragment read whole genome sequencing data using Illumina sequencing technology. Our method differs from the pre-existing TruSeq/Moleculo sequencing approach [24561555] in that it is based on compartmentalization of picogram quantities of starting DNA material (Figure 1A). Barcoding of individual wells enables obtaining a digital count of the number of wells that contained any particular allele. We hypothesized that this digital analysis of picogram quantities of DNA (DigiPico), would yield an accurate estimate of VAFs and, therefore, accurate calling of SCNAs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002268","title":"Mapping_gene_environment_interactions_in_macrophages","description":"Immune cells sense and respond to external stimuli such as pathogens and initiate an inflammatory response. Genetic variants altering the behaviour and responses of immune cells may inform the results of disease association studies and provide an insight into the regulation of immune response. \nStudies mapping quantitative trait loci (QTL) are usually performed in quiescent or naïve cells and therefore any variants with a condition-specific manner (e.g. those with an effect only detectable in a specific time-point after cell stimulation) are likely to remain undiscovered. So far, only a handful of studies have attempted to study QTL in multiple states and even on those studies the number of states has remained relatively low (&lt;5). Only very recently Horst and colleagues published the largest study to date investigating the effect of host variable (e.g. age, sex, contraceptive use etc.) on protein levels in macrophages stimulated with 19 different conditions (Horst et al, 2016). This project aims to develop a high-throughput experimental platform to detect QTL in a large number of states using iPSC derived macrophages.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Immune cells sense and respond to external stimuli such as pathogens and initiate an inflammatory response. Genetic variants altering the behaviour and responses of immune cells may inform the results of disease association studies and provide an insight into the regulation of immune response. \nStudies mapping quantitative trait loci (QTL) are usually performed in quiescent or naïve cells and therefore any variants with a condition-specific manner (e.g. those with an effect only detectable in a specific time-point after cell stimulation) are likely to remain undiscovered. So far, only a handful of studies have attempted to study QTL in multiple states and even on those studies the number of states has remained relatively low (&lt;5). Only very recently Horst and colleagues published the largest study to date investigating the effect of host variable (e.g. age, sex, contraceptive use etc.) on protein levels in macrophages stimulated with 19 different conditions (Horst et al, 2016). This project aims to develop a high-throughput experimental platform to detect QTL in a large number of states using iPSC derived macrophages.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-06T11:00:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002269","title":"Human_salmonella_vaccination","description":"1. HUman immunce cells were sorted after human vaccination with salmonella strains. Single cell transcriptomic analysis using smartseq2 protocol.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This study aims to better understand the human immune response to salmonella. In order to acheiev this we use human challenge models and single cell transcriptomic analysis.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002270","title":"Genomic profiling of Acute Lymphoblastic Leukemia in Ataxia Telangiectasia patients reveals tight link between ATM mutations and chromothripsis","description":"Recent developments in sequencing technologies led to the discovery of a novel form of genomic instability, termed chromothripsis. This catastrophic genomic event, involved in tumorigenesis, is characterized by tens to hundreds of simultaneously acquired locally clustered rearrangements on one chromosome. We hypothesized that leukemias developing in individuals with Ataxia Telangiectasia, who are born with two mutated copies of the ATM gene, an essential guardian of genome stability, would show a higher prevalence of chromothripsis due to the associated defect in DNA double-strand break repair. Using whole-genome sequencing, fluorescence in situ hybridization and RNA sequencing, we characterized the genomic landscape of Acute Lymphoblastic Leukemia (ALL) arising in patients with Ataxia Telangiectasia. We detected a high frequency of chromothriptic events in these tumors, specifically on acrocentric chromosomes, as compared to tumors from individuals with other types of DNA repair syndromes (27 cases total, 10 with Ataxia Telangiectasia). Our data suggest that the genomic landscape of Ataxia Telangiectasia ALL is clearly distinct from that of sporadic ALL. Mechanistically, short telomeres and compromised DNA damage response in cells of Ataxia Telangiectasia patients may be linked with frequent chromothripsis. Furthermore, we show that ATM loss is associated with increased chromothripsis prevalence in additional tumor entities.","abstract":"Recent developments in sequencing technologies led to the discovery of a novel form of genomic instability, termed chromothripsis. This catastrophic genomic event, involved in tumorigenesis, is characterized by tens to hundreds of simultaneously acquired locally clustered rearrangements on one chromosome. We hypothesized that leukemias developing in individuals with Ataxia Telangiectasia, who are born with two mutated copies of the ATM gene, an essential guardian of genome stability, would show a higher prevalence of chromothripsis due to the associated defect in DNA double-strand break repair. Using whole-genome sequencing, fluorescence in situ hybridization and RNA sequencing, we characterized the genomic landscape of Acute Lymphoblastic Leukemia (ALL) arising in patients with Ataxia Telangiectasia. We detected a high frequency of chromothriptic events in these tumors, specifically on acrocentric chromosomes, as compared to tumors from individuals with other types of DNA repair syndromes (27 cases total, 10 with Ataxia Telangiectasia). Our data suggest that the genomic landscape of Ataxia Telangiectasia ALL is clearly distinct from that of sporadic ALL. Mechanistically, short telomeres and compromised DNA damage response in cells of Ataxia Telangiectasia patients may be linked with frequent chromothripsis. Furthermore, we show that ATM loss is associated with increased chromothripsis prevalence in additional tumor entities.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-07T08:33:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002271","title":"Integrative analysis of whole genome sequencing, RNA sequencing and methylome array of 20 carcinosarcomas.","description":"Carcinosarcomas of the female genital tract, or GCS, are uncommon but clinically highly aggressive neoplasms with biphasic histology of carcinomatous (C) and sarcomatous (S) elements.  These tumors represent a unique model to study the genetic and phenotypic diversity of cancer cells and the link between cellular plasticity and resistance to therapy. The aim of ICGC GCS program is to genomically characterize C and S components of 20 tumors, from endometrium or ovary, through an integrative analysis of whole genome sequencing, RNA sequencing and methylome array.","abstract":"Carcinosarcomas of the female genital tract, or GCS, are uncommon but clinically highly aggressive neoplasms with biphasic histology of carcinomatous (C) and sarcomatous (S) elements.  These tumors represent a unique model to study the genetic and phenotypic diversity of cancer cells and the link between cellular plasticity and resistance to therapy. The aim of ICGC GCS program is to genomically characterize C and S components of 20 tumors, from endometrium or ovary, through an integrative analysis of whole genome sequencing, RNA sequencing and methylome array.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-07T11:36:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002272","title":"A no-stop mutation in MAGEB4 is a possible cause of rare X-linked azoospermia and oligozoospermia in a consanguineous Turkish family","description":"Purpose: The purpose of this study was to identify mutations that cause non-syndromic male infertility using whole exome sequencing of family cases.Methods: We recruited a consanguineous Turkish family comprising nine siblings with male triplets; two of the triplets were infertile as well as one younger infertile brother. Whole exome sequencing (WES) performed on two azoospermic brothers, identified a mutation in the MAGEB4 gene which was confirmed via Sanger sequencing and then screened for on control groups and unrelated infertile subjects. The effect of the mutation on mRNA and protein levels were tested after in vitro cell transfection. Structural features of MAGEB4 were predicted throughout the conserved MAGE domain.Results: The novel single base substitution (c.1041A&gt;T) in the X-linked MAGEB4 gene was identified as a no-stop mutation. The mutation is predicted to add 24 amino acids to the C-terminus of MAGEB4. Our functional studies were unable to detect any effect either on mRNA stability, intracellular localization of the protein or the ability to homo / heterodimerize with other MAGE proteins. We thus hypothesize that these additional amino acids may affect the proper protein interactions with MAGEB4 partners. Conclusion: The whole exome analysis of a consanguineous Turkish family revealed MAGEB4 as a possible new X-linked cause of inherited male infertility. This study provides the first clue to the physiological function of a MAGE protein.","abstract":"Purpose: The purpose of this study was to identify mutations that cause non-syndromic male infertility using whole exome sequencing of family cases.Methods: We recruited a consanguineous Turkish family comprising nine siblings with male triplets; two of the triplets were infertile as well as one younger infertile brother. Whole exome sequencing (WES) performed on two azoospermic brothers, identified a mutation in the MAGEB4 gene which was confirmed via Sanger sequencing and then screened for on control groups and unrelated infertile subjects. The effect of the mutation on mRNA and protein levels were tested after in vitro cell transfection. Structural features of MAGEB4 were predicted throughout the conserved MAGE domain.Results: The novel single base substitution (c.1041A&gt;T) in the X-linked MAGEB4 gene was identified as a no-stop mutation. The mutation is predicted to add 24 amino acids to the C-terminus of MAGEB4. Our functional studies were unable to detect any effect either on mRNA stability, intracellular localization of the protein or the ability to homo / heterodimerize with other MAGE proteins. We thus hypothesize that these additional amino acids may affect the proper protein interactions with MAGEB4 partners. Conclusion: The whole exome analysis of a consanguineous Turkish family revealed MAGEB4 as a possible new X-linked cause of inherited male infertility. This study provides the first clue to the physiological function of a MAGE protein.","study_type":"Other","pubmed_ids":[28401488],"external_links":null,"is_released":true,"released_date":"2017-02-08T10:13:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002273","title":"Genetic_Heterogeneity_of_the_familial_gastric_neuroendocrine_tumors","description":"Gastric neuroendocrine tumors (gNETs) occur with an estimated frequency of 2 per 100,000 in the general population.  Type I gastric neuroendocrine tumors (NETs) represent the 75% of gNTEs and arise from gastric enterochromaffin-like (ECL) cells.  They have late age of onset and usually benigh course.  Classically, hypergastrinemia in patients who have autoimmune atrophic gastritis, causes hyperplasia of gastric ECL cells that progresses into type I gastric NETs and parietal cell (PC) destruction.  The genetic bases in families with this disease are unknown.\nWe performed an exome sequencing study of an atypical aggressive familial gNETs case (with early age onset, nodal infiltrations and gastric adenocarcinomas) that followed a recessive model.  We identified a deleterious mutation in homozygosis in the ATP4A gene, which encodes the proton pump responsible for acid secretion by gastric parietal cells.  This mutation lead to achlorhydria first, and hypergastrinemia and gNET developing as consequence (Calvete et al. 2014).  Recently, two more families with gNETs, classical clinical traits and recessive model have been studies by WES but we didn't find any mutation in the ATP4a gene.  However, putative mutations affecting genes that contribute to the development and the integrity of PC have been found suggesting that genetic alterations associated to this disorder target to a unique cell type (parietal cells).\nIn order to cinfirm this hypothesis, it is necessary the search for new genes implicated in the gNETs, more familial cases are needed to be studied.  We have identified four more new familial gNETs cases.  Here, we propose their study by WES.  The first family is formed by thress siblings with gNETs.  The other families include two siblings with gNETs.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Gastric neuroendocrine tumors (gNETs) occur with an estimated frequency of 2 per 100,000 in the general population.  Type I gastric neuroendocrine tumors (NETs) represent the 75% of gNTEs and arise from gastric enterochromaffin-like (ECL) cells.  They have late age of onset and usually benigh course.  Classically, hypergastrinemia in patients who have autoimmune atrophic gastritis, causes hyperplasia of gastric ECL cells that progresses into type I gastric NETs and parietal cell (PC) destruction.  The genetic bases in families with this disease are unknown.\nWe performed an exome sequencing study of an atypical aggressive familial gNETs case (with early age onset, nodal infiltrations and gastric adenocarcinomas) that followed a recessive model.  We identified a deleterious mutation in homozygosis in the ATP4A gene, which encodes the proton pump responsible for acid secretion by gastric parietal cells.  This mutation lead to achlorhydria first, and hypergastrinemia and gNET developing as consequence (Calvete et al. 2014).  Recently, two more families with gNETs, classical clinical traits and recessive model have been studies by WES but we didn't find any mutation in the ATP4a gene.  However, putative mutations affecting genes that contribute to the development and the integrity of PC have been found suggesting that genetic alterations associated to this disorder target to a unique cell type (parietal cells).\nIn order to cinfirm this hypothesis, it is necessary the search for new genes implicated in the gNETs, more familial cases are needed to be studied.  We have identified four more new familial gNETs cases.  Here, we propose their study by WES.  The first family is formed by thress siblings with gNETs.  The other families include two siblings with gNETs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-08T10:24:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002274","title":"WGS_of_AML_during_PARPi_therapy","description":"We will require WGS on Illumina X10 machines of three samples, along with storage and computational power to perform the relevant analysis.","abstract":"The genetic bases of acute myeloid leukemia (AML) are increasingly well understood, with recurrent gene mutations and chromosomal translocations/copy number alterations driving the leukemic phenotype. However, the landscape of mutational processes behind those genomic events have never been thoroughly investigated. Here we propose to analyse a rare case of pure erythroid leukaemia (PEL) with a highly complex karyotype relapsing with a subclone carrying a whole-genome duplication event. This leukaemia was diagnosed as a secondary cancer in a patient carrying a germline BRCA2 inactivating mutation, affected by an ovarian cancer on PARP-inhibitor treatment. Tetraploid leukemias are exceptionally rare, and have never been characterised before by means of next-generation sequencing, nor their relationship with known defects of DNA repair pathways have ever been investigated.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-08T12:50:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002275","title":"Whole-genome Sequencing Suggests Mechanisms for 22q11.2 deletion-associated Parkinson’s disease","description":"Objectives: To investigate disease risk mechanisms of early-onset Parkinson’s disease (PD) associated with the recurrent 22q11.2 deletion, a genetic risk factor for early-onset PD.\nMethods: In a proof-of-principle study, we used whole-genome sequencing (WGS) to investigate sequence variants in nine adults with 22q11.2DS, three with neuropathologically confirmed early-onset PD and six without PD. Adopting an approach used recently to study schizophrenia in 22q11.2DS, here we tested candidate gene-sets relevant to PD.\nResults: No mutations common to the cases with PD were found in the intact 22q11.2 region. While all were negative for rare mutations in a gene-set comprising PD disease-causing and risk genes, another candidate gene-set of 1000 genes functionally relevant to PD presented a nominally significant (P=0.03) enrichment of rare putatively damaging missense variants in the PD cases. Polygenic score results, based on common variants associated with PD risk, were non-significantly greater in those with PD.\nConclusions: The results of this first-ever pilot study of WGS in PD suggest that the cumulative burden of genome-wide sequence variants may contribute to expression of early-onset PD in the presence of threshold-lowering dosage effects of a 22q11.2 deletion. We found no evidence that expression of PD in 22q11.2DS is mediated by a recessive locus on the intact 22q11.2 chromosome or mutations in known PD genes. These findings offer initial evidence of the potential effects of multiple within-individual rare variants on the expression of PD and the utility of next generation sequencing for studying the etiology of PD.","abstract":"Objectives: To investigate disease risk mechanisms of early-onset Parkinson’s disease (PD) associated with the recurrent 22q11.2 deletion, a genetic risk factor for early-onset PD.\nMethods: In a proof-of-principle study, we used whole-genome sequencing (WGS) to investigate sequence variants in nine adults with 22q11.2DS, three with neuropathologically confirmed early-onset PD and six without PD. Adopting an approach used recently to study schizophrenia in 22q11.2DS, here we tested candidate gene-sets relevant to PD.\nResults: No mutations common to the cases with PD were found in the intact 22q11.2 region. While all were negative for rare mutations in a gene-set comprising PD disease-causing and risk genes, another candidate gene-set of 1000 genes functionally relevant to PD presented a nominally significant (P=0.03) enrichment of rare putatively damaging missense variants in the PD cases. Polygenic score results, based on common variants associated with PD risk, were non-significantly greater in those with PD.\nConclusions: The results of this first-ever pilot study of WGS in PD suggest that the cumulative burden of genome-wide sequence variants may contribute to expression of early-onset PD in the presence of threshold-lowering dosage effects of a 22q11.2 deletion. We found no evidence that expression of PD in 22q11.2DS is mediated by a recessive locus on the intact 22q11.2 chromosome or mutations in known PD genes. These findings offer initial evidence of the potential effects of multiple within-individual rare variants on the expression of PD and the utility of next generation sequencing for studying the etiology of PD.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-08T16:29:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002276","title":"GWAS data (Illumina 2.5 M SNPs) in Cuban cohorts of dengue disease","description":"We will have 274 individuals typed for the Illumina Human Omni 2.5 chip. The individuals are from two locations in Cuba (Havana and Guantanamo) and from four phenotype classes (asymptomatic, control dengue fever and dengue hemorrhagic fever).","abstract":"We will have 274 individuals typed for the Illumina Human Omni 2.5 chip. The individuals are from two locations in Cuba (Havana and Guantanamo) and from four phenotype classes (asymptomatic, control dengue fever and dengue hemorrhagic fever).","study_type":"Other","pubmed_ids":[28241052],"external_links":null,"is_released":true,"released_date":"2017-02-08T16:51:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002277","title":"Mutational_signatures_in_carcinogen_induced_mouse_lung_tumours","description":"Human cancers arise through the combined effect of environmental exposures and endogenous mutagenesis resulting from factors such as replication stress and metabolism. Mouse and human tumour genome analyses have identified the mutational signatures of several known carcinogens, but many human cancers, including lung, carry specific signatures of exposure to agents that are as yet unknown. Here, we will address the question of how exposure to a wide variety of exogenous agents can shape genomic architecture. Specifically, we will characterize the mutational signatures of dozens of suspected/known human carcinogens used to induce hundreds of mouse tumours and then look for these signatures in human tumours. Other aspects of tumour biology will also be explored, such as the profile of the epigenome following carcinogen exposure, driver genes, and the effect that carcinogens have on the copy number landscape and profile of structural variants found in tumours.","abstract":"Human cancers arise through the combined effect of environmental exposures and endogenous mutagenesis resulting from factors such as replication stress and metabolism. Mouse and human tumour genome analyses have identified the mutational signatures of several known carcinogens, but many human cancers, including lung, carry specific signatures of exposure to agents that are as yet unknown. Here, we will address the question of how exposure to a wide variety of exogenous agents can shape genomic architecture. Specifically, we will characterize the mutational signatures of dozens of suspected/known human carcinogens used to induce hundreds of mouse tumours and then look for these signatures in human tumours. Other aspects of tumour biology will also be explored, such as the profile of the epigenome following carcinogen exposure, driver genes, and the effect that carcinogens have on the copy number landscape and profile of structural variants found in tumours.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002278","title":"Single_Cell_RNAseq_at_various_stages_of_HiPSCs_differentiating_toward_definitive_endoderm_and_endoderm_derived_lineages","description":"When comparing the differentiation capacities of pluripotent stem cell lines that have different\ngenetic backgrounds, batch to batch experimental variablility poses a significant challenge,\nespecially when trying to identify smaller effects. One way to address this issue is to\ndifferentiate several different lines in the same culture dish, thereby elimating experimental\nvariation. In addition, it allows researchers to analyze many more lines with less experiments.\nParallel single cell RNA-Seq exploits that individual cells are tagged and hence each cell can\nbe reliably assigned to the donor of origin based on the genetic variants it contains. In\naddition, analyzing the genetic signature of single cells within a differentiating population can\nreveal differentation stages that are not easily detected in bulk RNAseq data.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"When comparing the differentiation capacities of pluripotent stem cell lines that have different\ngenetic backgrounds, batch to batch experimental variablility poses a significant challenge,\nespecially when trying to identify smaller effects. One way to address this issue is to\ndifferentiate several different lines in the same culture dish, thereby elimating experimental\nvariation. In addition, it allows researchers to many examine more lines with less\nexperiments.\nParallel single cell RNA-Seq exploits that individual cells are tagged and hence each cell can\nbe reliably assigned to the donor of origin based on the genetic variants it contains. In\naddition, analyzing the genetic signature of single cells within a differentiating population can\nreveal differentation stages that are not easily detected in bulk RNAseq data.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-09T13:00:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002279","title":"adf","description":".","abstract":".","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002280","title":"Awesome study","description":"Wonderful ideas","abstract":"Wonderful ideas","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002281","title":"Study title","description":"abstract","abstract":"abstract","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002282","title":"title","description":"abstract","abstract":"abstract","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002283","title":"study title","description":"study abstract","abstract":"study abstract","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002284","title":"Study title","description":"Study abstract","abstract":"Study abstract","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002285","title":"Stitle","description":"Sabstract","abstract":"Sabstract","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002286","title":"fdsaf","description":"ds","abstract":"ds","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002287","title":"dsfas","description":"fas","abstract":"fas","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002288","title":"ee","description":"e","abstract":"e","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002289","title":"Study title","description":"Study abstract","abstract":"Study abstract","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002290","title":"fds","description":"fewqr","abstract":"fewqr","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002291","title":"Title","description":"ABS","abstract":"ABS","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002292","title":"Study 11","description":"Study 11","abstract":"Study 11","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002293","title":"A new Study","description":"An abstract","abstract":"An abstract","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002294","title":"Whole genome, whole exome, and targeted sequencing of high-grade meningioma tumor samples.","description":"High-grade meningiomas frequently recur and are associated with high rates of morbidity and mortality. To determine the factors that promote the development and evolution of these tumors, we analyzed the genomes of 274 high-grade meningiomas and compared this information with data from 456 low-grade meningiomas. High-grade meningiomas had a higher mutation burden than low-grade meningiomas but did not harbor any statistically significant mutated genes aside from NF2. High-grade meningiomas also possessed significantly elevated rates of chromosomal gains and losses, especially among tumors with monosomy 22. Meningiomas previously treated with adjuvant radiation had significantly more copy number alterations than radiation-induced or radiation-naïve meningiomas. Across serial recurrences, genomic disruption preceded the emergence of nearly all mutations, remained largely uniform across time, and when present in low-grade meningiomas, correlated with subsequent progression to a higher grade. In contrast to the largely stable copy number alterations, mutations were strikingly heterogeneous across tumor recurrences, likely due to extensive geographic heterogeneity in the primary tumor. While high-grade meningiomas harbored significantly fewer overtly targetable alterations than low-grade meningiomas, they contained numerous mutations that are predicted to be neoantigens, suggesting that immunologic targeting may be of therapeutic value.","abstract":"High-grade meningiomas frequently recur and are associated with high rates of morbidity and mortality. To determine the factors that promote the development and evolution of these tumors, we analyzed the genomes of 274 high-grade meningiomas and compared this information with data from 456 low-grade meningiomas. High-grade meningiomas had a higher mutation burden than low-grade meningiomas but did not harbor any statistically significant mutated genes aside from NF2. High-grade meningiomas also possessed significantly elevated rates of chromosomal gains and losses, especially among tumors with monosomy 22. Meningiomas previously treated with adjuvant radiation had significantly more copy number alterations than radiation-induced or radiation-naïve meningiomas. Across serial recurrences, genomic disruption preceded the emergence of nearly all mutations, remained largely uniform across time, and when present in low-grade meningiomas, correlated with subsequent progression to a higher grade. In contrast to the largely stable copy number alterations, mutations were strikingly heterogeneous across tumor recurrences, likely due to extensive geographic heterogeneity in the primary tumor. While high-grade meningiomas harbored significantly fewer overtly targetable alterations than low-grade meningiomas, they contained numerous mutations that are predicted to be neoantigens, suggesting that immunologic targeting may be of therapeutic value.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-11T19:47:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002295","title":"Study 100","description":"abstract","abstract":"abstract","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002296","title":"'PHn testing egasub tool for paca-ca submission'","description":"\"dafdafasdfdsafdafdfgdagd\"","abstract":"\"dafdafasdfdsafdafdfgdagd\"","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002297","title":"'HN testing 2'","description":"\"some abstract\"","abstract":"\"some abstract\"","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002298","title":"BGISEQ-500 Cancer Dataset - WGS tumour/normal pairs","description":"This study contains whole genome sequencing data for 3 matched tumour / normal pairs from Mesothelioma patients. The sequencing is 50bp paired-end generated using the BGISEQ-500 and is provided as 6 aligned and duplicate-marked BAM files.","abstract":"This study contains whole genome sequencing data for 3 matched tumour / normal pairs from Mesothelioma patients. The sequencing is 50bp paired-end generated using the BGISEQ-500 and is provided as 6 aligned and duplicate-marked BAM files.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-14T02:16:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002299","title":"Mesothelioma Genomics Study - WGS tumour/normal pairs","description":"Malignant mesothelioma (MM) is an incurable and aggressive tumour that occurs principally in the pleura as a consequence of inhaling asbestos fibres. There are &gt;15,000 cases per annum worldwide, the incidence is increasing and Australia has one of the world's highest incidence rates. Surgery, chemotherapy and radiotherapy (or their combinations) all feature in the clinical management but do not impact significantly on overall survival. This study uses whole genome sequencing (WGS) with the aim of identifying mesothelioma-related genomic alterations and potentially identifying novel treatment strategies.","abstract":"Malignant mesothelioma (MM) is an incurable and aggressive tumour that occurs principally in the pleura as a consequence of inhaling asbestos fibres. There are &gt;15,000 cases per annum worldwide, the incidence is increasing and Australia has one of the world's highest incidence rates. Surgery, chemotherapy and radiotherapy (or their combinations) all feature in the clinical management but do not impact significantly on overall survival. This study uses whole genome sequencing (WGS) with the aim of identifying mesothelioma-related genomic alterations and potentially identifying novel treatment strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-14T02:19:18+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002300","title":"LICA-CN project - 116 liver cancer cases","description":"LICA-CN project - 116 liver cancer cases","abstract":"LICA-CN project - 116 liver cancer cases","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-14T02:46:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002301","title":"Most HCCs in Taiwan show the mutational signature of aristolochic acid","description":"Plants in the genus Aristolochia contain the mutagen aristolochic acid (AA) and have been widely used in traditional medicines and for weight loss. AA binds covalently to genomic DNA and induces a highly distinctive mutational signature. While AA involvement in urinary-tract cancers in Taiwan is known, the possible role of AA in hepatocellular carcinomas (HCCs) in Taiwan has not been examined. Here, we whole-exome sequenced 98 unselected HCCs from Taiwan and analyzed the mutational signatures for evidence of AA mutagenesis. Remarkably, more than 78% of HCCs showed strong evidence of AA mutagenesis, often associated with high mutation burdens. Non-synonymous mutations in genes known to be HCC driver genes were detected. Importantly, we elucidated the potential of immunotherapy in this cohort of liver cancer patients.","abstract":"Plants in the genus Aristolochia contain the mutagen aristolochic acid (AA) and have been widely used in traditional medicines and for weight loss. AA binds covalently to genomic DNA and induces a highly distinctive mutational signature. While AA involvement in urinary-tract cancers in Taiwan is known, the possible role of AA in hepatocellular carcinomas (HCCs) in Taiwan has not been examined. Here, we whole-exome sequenced 98 unselected HCCs from Taiwan and analyzed the mutational signatures for evidence of AA mutagenesis. Remarkably, more than 78% of HCCs showed strong evidence of AA mutagenesis, often associated with high mutation burdens. Non-synonymous mutations in genes known to be HCC driver genes were detected. Importantly, we elucidated the potential of immunotherapy in this cohort of liver cancer patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-14T08:47:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002302","title":"A_single_cell_RNA_seq_approach_to_define_the_key_pro_fibrogenic_cells_in_liver_fibrosis","description":"Single cell RNA sequencing is transforming the way we think about disease pathogenesis, and allows the interrogation of individual pathogenic cell subpopulations with unprecedented resolution. Resident hepatic mesenchymal cells, which are the major source of scar deposition during liver fibrogenesis, have long been regarded as a functionally homogeneous population following liver injury. However, using a single cell RNAseq approach (SmartSeq2 protocol) in mouse models of hepatic fibrosis, we have found that the hepatic mesenchyme is comprised of multiple different cellular subpopulations, with highly variable pro-fibrotic phenotypes.\nIn this project we will use a droplet-based, high throughput single cell sequencing platform (10X Genomics) to interrogate the transcriptomes of thousands of mesenchymal cells from mouse models of liver fibrosis and also from normal and cirrhotic human livers. Critically, this high throughput approach will allow the identification of the key profibrogenic subpopulations driving human liver fibrosis with a very high degree of resolution, and will allow the identification of new, rational anti-fibrotic targets to treat patients with chronic liver disease. This project brings together Prof Ponting’s expertise in cutting-edge single cell bioinformatics approaches, and Prof Henderson’s expertise in the cellular and molecular mechanisms regulating liver fibrosis.","abstract":"Single cell RNA sequencing is transforming the way we think about disease pathogenesis, and allows the interrogation of individual pathogenic cell subpopulations with unprecedented resolution. Resident hepatic mesenchymal cells, which are the major source of scar deposition during liver fibrogenesis, have long been regarded as a functionally homogeneous population following liver injury. However, using a single cell RNAseq approach (SmartSeq2 protocol) in mouse models of hepatic fibrosis, we have found that the hepatic mesenchyme is comprised of multiple different cellular subpopulations, with highly variable pro-fibrotic phenotypes. \nIn this project we will use a droplet-based, high throughput single cell sequencing platform (10X Genomics) to interrogate the transcriptomes of thousands of mesenchymal cells from mouse models of liver fibrosis and also from normal and cirrhotic human livers. Critically, this high throughput approach will allow the identification of the key profibrogenic subpopulations driving human liver fibrosis with a very high degree of resolution, and will allow the identification of new, rational anti-fibrotic targets to treat patients with chronic liver disease.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002303","title":"PACA-CA Alignment Egasub testing","description":"asjdfkjdsakfljdsaklfjakdjf","abstract":"asjdfkjdsakfljdsaklfjakdjf","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002304","title":"Exome Analysis of the Evolutionary Path of Hepatic Adenoma-Carcinoma Transition, Vascular Invasion and Brain Dissemination","description":"Hepatocellular adenoma (HCA) is a rare benign liver tumor, predominantly seen in young women. Its major complications are malignant transformation, spontaneous hemorrhage, and rupture. We describe a case of a young female with no underlying liver disease who presented with a HCA, moderately differentiated hepatocellular carcinoma (HCC) and vascular invasion, which was followed by brain metastasis.To investigate the underlying genetic events occurring during hepatocellular adenoma-carcinoma transition and extra-hepatic dissemination, we performed whole exome sequencing for iperipheral blood leucocytes, HCA, HCC, tumor thrombus and brain metastasis. Our data show a step-wise addition of somatic mutations and copy number variations with disease progression, suggesting a linear tumor evolution, Our data highlight the feasibility of performing whole-exome capture, sequencing and analysis using FFPE samples, and we describe the first genomic longitudinal study of hepaticadenoma-carcinoma transition, vascular invasion and brain metastasis with detailed clinicopathologic annotation.","abstract":"Hepatocellular adenoma (HCA) is a rare benign liver tumor, predominantly seen in young women. Its major complications are malignant transformation, spontaneous hemorrhage, and rupture. We describe a case of a young female with no underlying liver disease who presented with a HCA, moderately differentiated hepatocellular carcinoma (HCC) and vascular invasion, which was followed by brain metastasis.To investigate the underlying genetic events occurring during hepatocellular adenoma-carcinoma transition and extra-hepatic dissemination, we performed whole exome sequencing for iperipheral blood leucocytes, HCA, HCC, tumor thrombus and brain metastasis. Our data show a step-wise addition of somatic mutations and copy number variations with disease progression, suggesting a linear tumor evolution, Our data highlight the feasibility of performing whole-exome capture, sequencing and analysis using FFPE samples, and we describe the first genomic longitudinal study of hepaticadenoma-carcinoma transition, vascular invasion and brain metastasis with detailed clinicopathologic annotation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002305","title":"The Ovarian Cancer Association Consortium OncoArray genome-wide association study","description":"A custom Illumina genotyping array, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers, and cancer-related traits. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis as described in PMID:27697780.The array was used to genotype  ovarian cancer cases and controls from multiple studies participating in the Ovarian Cancer Association Consortium, of which 54,747 passes QC.An initial principal components analysis was carried out using a method described in PMID:27697780 to assign subject to intercontinental ancestry groups: “European”, “African”, “Asian” and \"Other\".  Within ancestry principal components analysis was carried using a set of ~33k unlinked markers. Subsequent analyses were adjusted for the ancestry specific PCs: 9 Eur, 10 Asian, 1 African and 6 Mixed.  These PCs are included in the imputed dataset phenotypes file","abstract":"A custom Illumina genotyping array, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers, and cancer-related traits. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis as described in PMID:27697780.The array was used to genotype  ovarian cancer cases and controls from multiple studies participating in the Ovarian Cancer Association Consortium, of which 54,747 passes QC.An initial principal components analysis was carried out using a method described in PMID:27697780 to assign subject to intercontinental ancestry groups: “European”, “African”, “Asian” and \"Other\".  Within ancestry principal components analysis was carried using a set of ~33k unlinked markers. Subsequent analyses were adjusted for the ancestry specific PCs: 9 Eur, 10 Asian, 1 African and 6 Mixed.  These PCs are included in the imputed dataset phenotypes file","study_type":"Other","pubmed_ids":[27697780],"external_links":null,"is_released":true,"released_date":"2017-02-14T22:29:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002306","title":"Whole-Genome Sequencing of a Healthy Aging Cohort.","description":"Studies of long-lived individuals have revealed few genetic mechanisms for protection against age-associated disease. Therefore, we pursued genome sequencing of a related phenotype-healthy aging-to understand the genetics of disease-free aging without medical intervention. In contrast with studies of exceptional longevity, usually focused on centenarians, healthy aging is not associated with known longevity variants, but is associated with reduced genetic susceptibility to Alzheimer and coronary artery disease. Additionally, healthy aging is not associated with a decreased rate of rare pathogenic variants, potentially indicating the presence of disease-resistance factors. In keeping with this possibility, we identify suggestive common and rare variant genetic associations implying that protection against cognitive decline is a genetic component of healthy aging. These findings, based on a relatively small cohort, require independent replication. Overall, our results suggest healthy aging is an overlapping but distinct phenotype from exceptional longevity that may be enriched with disease-protective genetic factors.","abstract":"Studies of long-lived individuals have revealed few genetic mechanisms for protection against age-associated disease. Therefore, we pursued genome sequencing of a related phenotype-healthy aging-to understand the genetics of disease-free aging without medical intervention. In contrast with studies of exceptional longevity, usually focused on centenarians, healthy aging is not associated with known longevity variants, but is associated with reduced genetic susceptibility to Alzheimer and coronary artery disease. Additionally, healthy aging is not associated with a decreased rate of rare pathogenic variants, potentially indicating the presence of disease-resistance factors. In keeping with this possibility, we identify suggestive common and rare variant genetic associations implying that protection against cognitive decline is a genetic component of healthy aging. These findings, based on a relatively small cohort, require independent replication. Overall, our results suggest healthy aging is an overlapping but distinct phenotype from exceptional longevity that may be enriched with disease-protective genetic factors.","study_type":"Other","pubmed_ids":[27114037],"external_links":null,"is_released":true,"released_date":"2017-02-14T22:59:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002307","title":"Second study","description":"Abstract","abstract":"Abstract","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002308","title":"Predictor_BRCA_Xenograft","description":"Xenografts derived from patient tissues, and treated with drug therapies will be sequenced and computational worfklows used to identify mutations and derive mutational signature profiles. A BRCAness score for each sample will be dervied using bespoke algorithms. Samples displaying an enrichment in BRCA-like signatures will be correlated with their response to therapy in order to test whether there is an association between response and the BRCAness score.","abstract":"Xenografts derived from patient tissues, and treated with drug therapies will be sequenced and computational worfklows used to identify mutations and derive mutational signature profiles. A BRCAness score for each sample will be dervied using bespoke algorithms. Samples displaying an enrichment in BRCA-like signatures will be correlated with their response to therapy in order to test whether there is an association between response and the BRCAness score.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002309","title":"Next_gen_seq_of_eye_cancers","description":"Retinoblastoma (RB), the commonest eye cancer in children was the first cancer for which a genetic cause was identified: the Rb1 gene is a tumour suppressor gene that is mutated in RB. \nThe Rb1 gene defect alone does not predict the clinical outcome. We propose to study other possible mechanisms:\n1. Stepwise further mutations occur in RB, increasing its carcinogenesis. We will sequence the whole genome in RB tissue, and relate the different genes expressed to the treatments used.\n2. Extracellular matric proteins contribute to a tumour permissive environment for RB to continue to grow. This includes Samll Leucine Rich Proteoglycans (SLRP), a family of 15 secreted extracellular matrix proteins involved in eye development.\n3. Cancer stem cells (CSC), a subpopulation of treatment resistant cells, drive RB tumours, and whether these stem cells can be manipulated for new therapies.\n\nThe aim of this study is to assist finding targeted diagnostic techniques and treatments for RB.","abstract":"Retinoblastoma (RB), the commonest eye cancer in children was the first cancer for which a genetic cause was identified: the Rb1 gene is a tumour suppressor gene that is mutated in RB. \nThe Rb1 gene defect alone does not predict the clinical outcome. We propose to study other possible mechanisms:\n1. Stepwise further mutations occur in RB, increasing its carcinogenesis. We will sequence the whole genome in RB tissue, and relate the different genes expressed to the treatments used.\n2. Extracellular matric proteins contribute to a tumour permissive environment for RB to continue to grow. This includes Samll Leucine Rich Proteoglycans (SLRP), a family of 15 secreted extracellular matrix proteins involved in eye development.\n3. Cancer stem cells (CSC), a subpopulation of treatment resistant cells, drive RB tumours, and whether these stem cells can be manipulated for new therapies.\n\nThe aim of this study is to assist finding targeted diagnostic techniques and treatments for RB.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-15T15:52:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002310","title":"'My test study'","description":"'ajkdfjaksdjfkasjdf'","abstract":"'ajkdfjaksdjfkasjdf'","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002311","title":"ICGC Pancreatic Cancer study","description":"Pancreatic Cancer whole genome sequencing of 112 samples","abstract":"Pancreatic Cancer whole genome sequencing of 112 samples","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002312","title":"Whole-exome sequencing of PTC, benign nodule and normal tissues in 28 patients","description":"In order to comprehensively investigate the genetic relationship between PTC tumors and benign nodules, we totally collected 127 fresh-frozen biopsies samples from 28 patients with concurrent thyroid benign nodule and PTC (n=20) or simple benign nodule (n=8). We carried out whole-exome sequencing  on all the 127 biopsies samples and RNA-sequencing in total of 40 samples.","abstract":"In order to comprehensively investigate the genetic relationship between PTC tumors and benign nodules, we totally collected 127 fresh-frozen biopsies samples from 28 patients with concurrent thyroid benign nodule and PTC (n=20) or simple benign nodule (n=8). We carried out whole-exome sequencing  on all the 127 biopsies samples and RNA-sequencing in total of 40 samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-16T13:49:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002313","title":"There are 340 cases belongs to ICGC GACA-CN project.","description":"There are 340 cases belongs to ICGC GACA-CN project.","abstract":"There are 340 cases belongs to ICGC GACA-CN project.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002314","title":"Sequencing of paediatric High Grade Gliomas and DIPG","description":"Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are a phenotypically diverse collection of tumours which molecular profiling studies have refined into age- and location-based subgroups driven by unique genetic and epigenetic alterations. Despite this, the rarity of these tumours means individual studies are underpowered to investigate subgroup-specific changes and to identify low frequency events recurrently targeting specific pathways. We have collated genomic data from 143 unpublished cases up to 30 years of age along with those from 18 previously published datasets in an integrated analysis comprising 1067 unique patients across all anatomical compartments of the CNS, with histone mutation status available for 893 cases (n=67 H3.3G34R/V, n=316 H3.3K27M, n=68 H3.1/H3.2K27M). Distinct clinicopathological and molecular subgroups are defined by these histone mutations, with several novel co-segregating mutations identified through these aggregated analyses, including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups can be further refined by the presence of key oncogenic events (PDGFRA or EGFR amplification/mutations) or methylation profiles which molecularly more closely resemble pleomorphic xanthoastrocytoma or other low grade gliomas. The burden of genomic aberrations decreases with age, highlighting the infant population as biologically and clinically distinct. Across the whole cohort, we identify novel previously unrecognised pathway dysregulation in small subsets of tumours (e.g. splicing, WNT, immune response) which make up the umbrella classification of paediatric diffusely infiltrating gliomas. The integrated dataset helps to further define the molecular diversity of the disease, opening up novel avenues for biological study and providing a basis for functionally defined future treatment stratification.","abstract":"Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are a phenotypically diverse collection of tumours which molecular profiling studies have refined into age- and location-based subgroups driven by unique genetic and epigenetic alterations. Despite this, the rarity of these tumours means individual studies are underpowered to investigate subgroup-specific changes and to identify low frequency events recurrently targeting specific pathways. We have collated genomic data from 143 unpublished cases up to 30 years of age along with those from 18 previously published datasets in an integrated analysis comprising 1067 unique patients across all anatomical compartments of the CNS, with histone mutation status available for 893 cases (n=67 H3.3G34R/V, n=316 H3.3K27M, n=68 H3.1/H3.2K27M). Distinct clinicopathological and molecular subgroups are defined by these histone mutations, with several novel co-segregating mutations identified through these aggregated analyses, including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups can be further refined by the presence of key oncogenic events (PDGFRA or EGFR amplification/mutations) or methylation profiles which molecularly more closely resemble pleomorphic xanthoastrocytoma or other low grade gliomas. The burden of genomic aberrations decreases with age, highlighting the infant population as biologically and clinically distinct. Across the whole cohort, we identify novel previously unrecognised pathway dysregulation in small subsets of tumours (e.g. splicing, WNT, immune response) which make up the umbrella classification of paediatric diffusely infiltrating gliomas. The integrated dataset helps to further define the molecular diversity of the disease, opening up novel avenues for biological study and providing a basis for functionally defined future treatment stratification.","study_type":"Other","pubmed_ids":[5637314],"external_links":null,"is_released":true,"released_date":"2017-02-21T13:00:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002315","title":"ImmunoAgeing_TGS","description":"An investigation of the role of immunosenescence in the development of clonal haematopoiesis.","abstract":"The objective is to establish whether immunosenescence is associated with the development of clonal haematopoiesis in a healthy ageing population. This will be addressed in collaboration with the European consortium running the ImmunoAgeing project (www.immunoageing.eu).   \nGenomic DNA derived from the peripheral blood of 300 individuals will be analysed. RNA bait pulldown (Agilent) will be used to perform targeted sequencing of 41 genes known to be recurrently mutated in myeloid malignancies. In addition, a subset of 15 individuals will be analysed using whole exome sequencing. \nThe presence, size and nature of clonal haematopoiesis will be correlated with quantitative measures of immunosenescence.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002316","title":"ImmunoAgeing_WES","description":"An investigation of the role of immunosenescence in the development of clonal haematopoiesis.","abstract":"The objective is to establish whether immunosenescence is associated with the development of clonal haematopoiesis in a healthy ageing population. This will be addressed in collaboration with the European consortium running the ImmunoAgeing project (www.immunoageing.eu).   \nGenomic DNA derived from the peripheral blood of 300 individuals will be analysed. RNA bait pulldown (Agilent) will be used to perform targeted sequencing of 41 genes known to be recurrently mutated in myeloid malignancies. In addition, a subset of 15 individuals will be analysed using whole exome sequencing. \nThe presence, size and nature of clonal haematopoiesis will be correlated with quantitative measures of immunosenescence.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002317","title":"18 Whole Exome Sequencing for Radiation Induced-Meningiomas","description":"Purpose: Majority of pediatric cancers require the irradiation of the central nervous system (CNS), and as more patients survive into adulthood from improved oncological therapy the sequelae of brain radiation are increasing in prevalence. Radiation-induced meningiomas (RIMs), one such secondary effect, demonstrate a clinically more aggressive behaviour than sporadic meningiomas (SMs). We aimed to describe the genomic mutational landscape of RIMs.Methods:  We analyzed a principal cohort of 18 RIMs, with 31 RIMs overall, from patients who received childhood radiation therapy and 30 SMs, as a comparator population. We performed a multiplatform integrative genomic analysis; including methylation, whole exome and RNA sequencing. Results: RIMs exhibited a five-fold increase in copy number alterations, commonly the loss of chromosome 1p (17/18 RIMs) and 22q (17/18 RIMs), which was significantly more than observed in sporadic meningiomas. Furthermore, RNA sequencing data revealed an NF2 gene fusion event in 35.3% of RIMs. In all 6 cases, there was a complete NF2 exon spliced into a complete exon of a reciprocal gene, suggesting that the breakpoints of genomic rearrangement are intronic. All tumours with the NF2 fusion also possessed monosomy of chromosome 22q, rendering the cells with homozygous disruption of NF2. Clinically, RIMs with the NF2 fusion exhibited ill-defined borders and a tendency to develop in anatomic frontal location. Also, targeted sequencing panel confirmed that RIMs had fewer nonsynonymous NF2 mutations (6.5% vs. 30% in SM) and absence of mutations in TRAF7, SMO, KLF4, PIK3CA and AKT1, genes traditionally involved in SMs.Conclusion: Our study demonstrates that RIMs have distinct genomic drivers of oncogenesis as compared to SMs, specifically NF2 inactivation through fusion event. Radiation therapy possibly triggers genomic structural rearrangements through error-prone repair of double-stranded DNA breaks.","abstract":"Purpose: Majority of pediatric cancers require the irradiation of the central nervous system (CNS), and as more patients survive into adulthood from improved oncological therapy the sequelae of brain radiation are increasing in prevalence. Radiation-induced meningiomas (RIMs), one such secondary effect, demonstrate a clinically more aggressive behaviour than sporadic meningiomas (SMs). We aimed to describe the genomic mutational landscape of RIMs.Methods:  We analyzed a principal cohort of 18 RIMs, with 31 RIMs overall, from patients who received childhood radiation therapy and 30 SMs, as a comparator population. We performed a multiplatform integrative genomic analysis; including methylation, whole exome and RNA sequencing. Results: RIMs exhibited a five-fold increase in copy number alterations, commonly the loss of chromosome 1p (17/18 RIMs) and 22q (17/18 RIMs), which was significantly more than observed in sporadic meningiomas. Furthermore, RNA sequencing data revealed an NF2 gene fusion event in 35.3% of RIMs. In all 6 cases, there was a complete NF2 exon spliced into a complete exon of a reciprocal gene, suggesting that the breakpoints of genomic rearrangement are intronic. All tumours with the NF2 fusion also possessed monosomy of chromosome 22q, rendering the cells with homozygous disruption of NF2. Clinically, RIMs with the NF2 fusion exhibited ill-defined borders and a tendency to develop in anatomic frontal location. Also, targeted sequencing panel confirmed that RIMs had fewer nonsynonymous NF2 mutations (6.5% vs. 30% in SM) and absence of mutations in TRAF7, SMO, KLF4, PIK3CA and AKT1, genes traditionally involved in SMs.Conclusion: Our study demonstrates that RIMs have distinct genomic drivers of oncogenesis as compared to SMs, specifically NF2 inactivation through fusion event. Radiation therapy possibly triggers genomic structural rearrangements through error-prone repair of double-stranded DNA breaks.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-21T14:28:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002318","title":"RNA seq on 19 samples of Radiation-Induced Meningiomas","description":"Purpose: Majority of pediatric cancers require the irradiation of the central nervous system (CNS), and as more patients survive into adulthood from improved oncological therapy the sequelae of brain radiation are increasing in prevalence. Radiation-induced meningiomas (RIMs), one such secondary effect, demonstrate a clinically more aggressive behaviour than sporadic meningiomas (SMs). We aimed to describe the genomic mutational landscape of RIMs.Methods:  We analyzed a principal cohort of 18 RIMs, with 31 RIMs overall, from patients who received childhood radiation therapy and 30 SMs, as a comparator population. We performed a multiplatform integrative genomic analysis; including methylation, whole exome and RNA sequencing. Results: RIMs exhibited a five-fold increase in copy number alterations, commonly the loss of chromosome 1p (17/18 RIMs) and 22q (17/18 RIMs), which was significantly more than observed in sporadic meningiomas. Furthermore, RNA sequencing data revealed an NF2 gene fusion event in 35.3% of RIMs. In all 6 cases, there was a complete NF2 exon spliced into a complete exon of a reciprocal gene, suggesting that the breakpoints of genomic rearrangement are intronic. All tumours with the NF2 fusion also possessed monosomy of chromosome 22q, rendering the cells with homozygous disruption of NF2. Clinically, RIMs with the NF2 fusion exhibited ill-defined borders and a tendency to develop in anatomic frontal location. Also, targeted sequencing panel confirmed that RIMs had fewer nonsynonymous NF2 mutations (6.5% vs. 30% in SM) and absence of mutations in TRAF7, SMO, KLF4, PIK3CA and AKT1, genes traditionally involved in SMs.Conclusion: Our study demonstrates that RIMs have distinct genomic drivers of oncogenesis as compared to SMs, specifically NF2 inactivation through fusion event. Radiation therapy possibly triggers genomic structural rearrangements through error-prone repair of double-stranded DNA breaks.","abstract":"Purpose: Majority of pediatric cancers require the irradiation of the central nervous system (CNS), and as more patients survive into adulthood from improved oncological therapy the sequelae of brain radiation are increasing in prevalence. Radiation-induced meningiomas (RIMs), one such secondary effect, demonstrate a clinically more aggressive behaviour than sporadic meningiomas (SMs). We aimed to describe the genomic mutational landscape of RIMs.Methods:  We analyzed a principal cohort of 18 RIMs, with 31 RIMs overall, from patients who received childhood radiation therapy and 30 SMs, as a comparator population. We performed a multiplatform integrative genomic analysis; including methylation, whole exome and RNA sequencing. Results: RIMs exhibited a five-fold increase in copy number alterations, commonly the loss of chromosome 1p (17/18 RIMs) and 22q (17/18 RIMs), which was significantly more than observed in sporadic meningiomas. Furthermore, RNA sequencing data revealed an NF2 gene fusion event in 35.3% of RIMs. In all 6 cases, there was a complete NF2 exon spliced into a complete exon of a reciprocal gene, suggesting that the breakpoints of genomic rearrangement are intronic. All tumours with the NF2 fusion also possessed monosomy of chromosome 22q, rendering the cells with homozygous disruption of NF2. Clinically, RIMs with the NF2 fusion exhibited ill-defined borders and a tendency to develop in anatomic frontal location. Also, targeted sequencing panel confirmed that RIMs had fewer nonsynonymous NF2 mutations (6.5% vs. 30% in SM) and absence of mutations in TRAF7, SMO, KLF4, PIK3CA and AKT1, genes traditionally involved in SMs.Conclusion: Our study demonstrates that RIMs have distinct genomic drivers of oncogenesis as compared to SMs, specifically NF2 inactivation through fusion event. Radiation therapy possibly triggers genomic structural rearrangements through error-prone repair of double-stranded DNA breaks.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-21T16:11:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002319","title":"Whole exome sequencing in RVOT patients","description":"In a patient with right ventricular outflow tract (RVOT) tachycardia we identified a heterozygous point mutation in the selectivity filter of the stretch-activated K2P potassium channel TREK-1 (KCNK2 or K2P2.1). This mutation introduces abnormal sodium permeability to TREK-1 In addition, mutant channels exhibit a hypersensitivity to stretch-activation, suggesting that the selectivity filter is directly involved in stretch-induced activation and desensitization. Increased sodium permeability and stretch-sensitivity of mutant TREK-1 channels may trigger arrhythmias in areas of the heart with high physical strain such as the RVOT. We present a pharmacological strategy to rescue the selectivity defect of the TREK-1 pore. Our findings provide important insights for future studies of K2P channel stretch-activation and the role of TREK-1 in mechano-electrical feedback in the heart.","abstract":"In a patient with right ventricular outflow tract (RVOT) tachycardia we identified a heterozygous point mutation in the selectivity filter of the stretch-activated K2P potassium channel TREK-1 (KCNK2 or K2P2.1). This mutation introduces abnormal sodium permeability to TREK-1 In addition, mutant channels exhibit a hypersensitivity to stretch-activation, suggesting that the selectivity filter is directly involved in stretch-induced activation and desensitization. Increased sodium permeability and stretch-sensitivity of mutant TREK-1 channels may trigger arrhythmias in areas of the heart with high physical strain such as the RVOT. We present a pharmacological strategy to rescue the selectivity defect of the TREK-1 pore. Our findings provide important insights for future studies of K2P channel stretch-activation and the role of TREK-1 in mechano-electrical feedback in the heart.","study_type":"Other","pubmed_ids":[28219978],"external_links":null,"is_released":true,"released_date":"2017-02-22T16:13:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002320","title":"Massively parallel nanowell-based single-cell gene expression profiling","description":"Technological advances have enabled transcriptome characterization of cell types at the single-cell level providing new biological insights. New methods that enable simple yet high-throughput single-cell expression profiling are highly desirable. Here we report a novel nanowell-based single-cell RNA sequencing system, ICELL8, which enables processing of thousands of cells per sample. The system employs a 5184-nanowell-containing microchip to capture ~1300 single cells and process them. Each nanowell contains preprinted oligonucleotides encoding poly-d(T), a unique well barcode, and a unique molecular identifier. The ICELL8 system uses imaging software to identify nanowells containing viable single cells and only wells with single cells are processed into sequencing libraries. Here, we report the performance and utility of ICELL8 using samples of increasing complexity from cultured cells to mouse solid tissue samples. Our assessment of the system to discriminate between mixed human and mouse cells showed that ICELL8 has a low cell multiplet rate (&lt; 3%) and low cross-cell contamination. We characterized single-cell transcriptomes of more than a thousand cultured human and mouse cells as well as 468 mouse pancreatic islets cells. We were able to identify distinct cell types in pancreatic islets, including alpha, beta, delta and gamma cells. Overall, ICELL8 provides efficient and cost-effective single-cell expression profiling of thousands of cells, allowing researchers to decipher single-cell transcriptomes within complex biological samples.","abstract":"Technological advances have enabled transcriptome characterization of cell types at the single-cell level providing new biological insights. New methods that enable simple yet high-throughput single-cell expression profiling are highly desirable. Here we report a novel nanowell-based single-cell RNA sequencing system, ICELL8, which enables processing of thousands of cells per sample. The system employs a 5184-nanowell-containing microchip to capture ~1300 single cells and process them. Each nanowell contains preprinted oligonucleotides encoding poly-d(T), a unique well barcode, and a unique molecular identifier. The ICELL8 system uses imaging software to identify nanowells containing viable single cells and only wells with single cells are processed into sequencing libraries. Here, we report the performance and utility of ICELL8 using samples of increasing complexity from cultured cells to mouse solid tissue samples. Our assessment of the system to discriminate between mixed human and mouse cells showed that ICELL8 has a low cell multiplet rate (&lt; 3%) and low cross-cell contamination. We characterized single-cell transcriptomes of more than a thousand cultured human and mouse cells as well as 468 mouse pancreatic islets cells. We were able to identify distinct cell types in pancreatic islets, including alpha, beta, delta and gamma cells. Overall, ICELL8 provides efficient and cost-effective single-cell expression profiling of thousands of cells, allowing researchers to decipher single-cell transcriptomes within complex biological samples.","study_type":"Other","pubmed_ids":[28687070],"external_links":null,"is_released":true,"released_date":"2017-02-22T17:25:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002321","title":"Functional_genomics_approaches_to_understand_osteoarthritis","description":"The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of large joint (hip and knee) osteoarthritis which culminates in the need for total joint replacement (TJR). We will obtain diseased and non-diseased cartilage as well as other disease-relevant tissue following TJR, coupled with a blood sample. We will generate genotype data and will characterise the pairs of diseased and non-diseased tissue samples in terms of methylation, transcription (RNASeq) and expression (quantitative proteomics).  We will apply integrative approaches to combine information across the –omics levels to characterise genes, pathways, and networks that underlie osteoarthritis progression.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of large joint (hip and knee) osteoarthritis which culminates in the need for total joint replacement (TJR). We will obtain diseased and non-diseased cartilage as well as other disease-relevant tissue following TJR, coupled with a blood sample. We will generate genotype data and will characterise the pairs of diseased and non-diseased tissue samples in terms of methylation, transcription (RNASeq) and expression (quantitative proteomics).  We will apply integrative approaches to combine information across the –omics levels to characterise genes, pathways, and networks that underlie osteoarthritis progression.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002322","title":"Functional_genomics_approaches_to_understand_osteoarthritis","description":"The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of large joint (hip and knee) osteoarthritis which culminates in the need for total joint replacement (TJR). We will obtain diseased and non-diseased cartilage as well as other disease-relevant tissue following TJR, coupled with a blood sample. We will generate genotype data and will characterise the pairs of diseased and non-diseased tissue samples in terms of methylation, transcription (RNASeq) and expression (quantitative proteomics).  We will apply integrative approaches to combine information across the –omics levels to characterise genes, pathways, and networks that underlie osteoarthritis progression.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of large joint (hip and knee) osteoarthritis which culminates in the need for total joint replacement (TJR). We will obtain diseased and non-diseased cartilage as well as other disease-relevant tissue following TJR, coupled with a blood sample. We will generate genotype data and will characterise the pairs of diseased and non-diseased tissue samples in terms of methylation, transcription (RNASeq) and expression (quantitative proteomics).  We will apply integrative approaches to combine information across the –omics levels to characterise genes, pathways, and networks that underlie osteoarthritis progression.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-23T11:56:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002323","title":"The Immune Microenvironment, Genome–Wide Copy Number Aberrations and Survival in Mesothelioma","description":"IntroductionResults of recent clinical studies of immune checkpoint inhibitors in malignant pleural mesothelioma (MPM) have dampened initial enthusiasm. However, the immune environment and targets of these treatments such as program cell death protein 1 (PD-1) and its ligand PD-L1 have not been well characterised in MPM. Using a large cohort of patients, we investigated PD-L1 expression, immune infiltrates and genome-wide copy number status and correlated them to clinicopathological features.Patients and methodsTissue microarrays were constructed and stained with PD-L1(clone E1L3N, CST), CD4, CD8 and FOXP3 antibodies. PD-L1 positivity was defined as ≥5% membranous staining regardless of intensity and PD-L1+hi as ≥50%. Genomic DNA from a representative subset of 113 patients was used for genome-wide copy number analysis. The percent genome alteration (PGA) was computed as a proxy for genomic instability, and statistical analyses were used to relate copy number aberrations (CNA) to other variables.ResultsAmongst 329 patients evaluated, PD-L1+ was detected in 130/311 (41.7%), but PD-L1+hi was only seen in 30/311 (9.6%). PD-L1+ correlated with non–epithelioid histology and increased infiltration with CD4+, CD8+ and FOXP3+ lymphocytes. PD-L1+hi expression correlated with worse prognosis (HR = 2.37; 95%CI= 1.57-3.56; P &lt; 0.001) on univariate analysis, but not in multivariate analysis. Higher PGA was associated with epithelioid histology and poorer survival (HR = 1.59; 95%CI= 1.01-2.5; P = 0.04), but not PD-L1 expression.ConclusionPD-L1 expression was associated with non-epithelioid MPM, poor clinical outcome and increased immunological infiltrates. Increased genomic instability did not correlate with PD-L1 expression, but was associated with poorer survival.","abstract":"IntroductionResults of recent clinical studies of immune checkpoint inhibitors in malignant pleural mesothelioma (MPM) have dampened initial enthusiasm. However, the immune environment and targets of these treatments such as program cell death protein 1 (PD-1) and its ligand PD-L1 have not been well characterised in MPM. Using a large cohort of patients, we investigated PD-L1 expression, immune infiltrates and genome-wide copy number status and correlated them to clinicopathological features.Patients and methodsTissue microarrays were constructed and stained with PD-L1(clone E1L3N, CST), CD4, CD8 and FOXP3 antibodies. PD-L1 positivity was defined as ≥5% membranous staining regardless of intensity and PD-L1+hi as ≥50%. Genomic DNA from a representative subset of 113 patients was used for genome-wide copy number analysis. The percent genome alteration (PGA) was computed as a proxy for genomic instability, and statistical analyses were used to relate copy number aberrations (CNA) to other variables.ResultsAmongst 329 patients evaluated, PD-L1+ was detected in 130/311 (41.7%), but PD-L1+hi was only seen in 30/311 (9.6%). PD-L1+ correlated with non–epithelioid histology and increased infiltration with CD4+, CD8+ and FOXP3+ lymphocytes. PD-L1+hi expression correlated with worse prognosis (HR = 2.37; 95%CI= 1.57-3.56; P &lt; 0.001) on univariate analysis, but not in multivariate analysis. Higher PGA was associated with epithelioid histology and poorer survival (HR = 1.59; 95%CI= 1.01-2.5; P = 0.04), but not PD-L1 expression.ConclusionPD-L1 expression was associated with non-epithelioid MPM, poor clinical outcome and increased immunological infiltrates. Increased genomic instability did not correlate with PD-L1 expression, but was associated with poorer survival.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-23T18:25:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002324","title":"Genome-to-genome analysis highlights the impact of the human innate and adaptive immune systems on the hepatitis C virus","description":"Outcomes of hepatitis C virus (HCV) infection and treatment depend on viral and host genetic factors. We use human genome-wide genotyping arrays and new whole-genome HCV viral sequencing technologies to perform a systematic genome-to-genome study of 542 individuals chronically infected with HCV, predominately genotype 3. We show that both HLA alleles and interferon lambda innate immune system genes drive viral genome polymorphism, and that IFNL4 genotypes determine HCV viral load through a mechanism that is dependent on a specific polymorphism in the HCV polyprotein. We highlight the interplay between innate immune responses and the viral genome in HCV control.","abstract":"Outcomes of hepatitis C virus (HCV) infection and treatment depend on viral and host genetic factors. We use human genome-wide genotyping arrays and new whole-genome HCV viral sequencing technologies to perform a systematic genome-to-genome study of 542 individuals chronically infected with HCV, predominately genotype 3. We show that both HLA alleles and interferon lambda innate immune system genes drive viral genome polymorphism, and that IFNL4 genotypes determine HCV viral load through a mechanism that is dependent on a specific polymorphism in the HCV polyprotein. We highlight the interplay between innate immune responses and the viral genome in HCV control.","study_type":"Other","pubmed_ids":[28394351],"external_links":null,"is_released":true,"released_date":"2017-02-24T12:22:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002325","title":"Kidney_Single_Cell_Study","description":"We intend to use single cell transcriptome analysis to explore the heterogenity of different cell types within the kidney.","abstract":"We intend to use single cell transcriptome analysis to explore the heterogenity of different cell types within the kidney.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-24T12:58:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002326","title":"Whole exome sequencing of an invasive diffuse intrinsic pontine glioma sampled from different sites","description":"The lateral ventricle subventricular zone (SVZ) is a frequent site of high-grade glioma (HGG) spread and tumor invasion of the SVZ is a predictor of a worse clinical prognosis. A range of HGG types invade the stem cell niche of the SVZ, including both adult glioblastoma and pediatric high-grade gliomas such as diffuse intrinsic pontine glioma (DIPG). The cellular and molecular mechanisms mediating this frequent invasion of the SVZ are poorly understood. Here we demonstrate that neural precursor cell (NPC):glioma cell communication underpins the propensity of glioma to colonize the SVZ. SVZ NPCs secrete chemoattractant signals toward which glioma cells home. Biochemical and proteomic analyses of factors secreted by SVZ NPCs revealed a discrete list of candidate proteins. Necessity and sufficiency testing implicated the neurite outgrowth-promoting factor pleiotrophin, along with three required binding partners (secreted protein acidic and rich in cysteine (SPARC), SPARC-like protein 1, and heat shock protein 90B), as key mediators of this chemoattractant effect. Pleiotrophin protein expression is strongly enriched in the SVZ, and knockdown of pleiotrophin expression starkly reduced glioma invasion of the SVZ in the adult murine brain.  Pleiotrophin, in complex with the three binding partners, activated the Rho/ROCK pathway in DIPG cells, and inhibition of ROCK resulted in decreased DIPG invasion toward SVZ neural precursor cell-secreted factors. These findings demonstrate a pathogenic role for neural precursor cell – glioma interactions and potential therapeutic targets to limit glioma invasion.","abstract":"The lateral ventricle subventricular zone (SVZ) is a frequent site of high-grade glioma (HGG) spread and tumor invasion of the SVZ is a predictor of a worse clinical prognosis. A range of HGG types invade the stem cell niche of the SVZ, including both adult glioblastoma and pediatric high-grade gliomas such as diffuse intrinsic pontine glioma (DIPG). The cellular and molecular mechanisms mediating this frequent invasion of the SVZ are poorly understood. Here we demonstrate that neural precursor cell (NPC):glioma cell communication underpins the propensity of glioma to colonize the SVZ. SVZ NPCs secrete chemoattractant signals toward which glioma cells home. Biochemical and proteomic analyses of factors secreted by SVZ NPCs revealed a discrete list of candidate proteins. Necessity and sufficiency testing implicated the neurite outgrowth-promoting factor pleiotrophin, along with three required binding partners (secreted protein acidic and rich in cysteine (SPARC), SPARC-like protein 1, and heat shock protein 90B), as key mediators of this chemoattractant effect. Pleiotrophin protein expression is strongly enriched in the SVZ, and knockdown of pleiotrophin expression starkly reduced glioma invasion of the SVZ in the adult murine brain.  Pleiotrophin, in complex with the three binding partners, activated the Rho/ROCK pathway in DIPG cells, and inhibition of ROCK resulted in decreased DIPG invasion toward SVZ neural precursor cell-secreted factors. These findings demonstrate a pathogenic role for neural precursor cell – glioma interactions and potential therapeutic targets to limit glioma invasion.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-27T10:12:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002327","title":"Test Study for EGA distribution tests using 1000 Genomes Phase 3 data","description":"Test Study for EGA distribution tests using 1000 Genomes Phase 3 data","abstract":"Test Study for EGA distribution tests using 1000 Genomes Phase 3 data","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002328","title":"Genomic profiling of paediatric high grade gliomas from the HERBY clinical trial","description":"The HERBY trial was a phase-II open-label, randomised, multicentre trial evaluating bevacizumab in patients with newly-diagnosed non-brainstem high grade glioma (HGG) between the ages of 3-18yrs. 121 patients were randomised with 1yr event-free survival as the primary end-point. Confirmation of HGG diagnosis by  reference pathology was mandatory before randomisation, followed by review with five independent expert neuropathologists. We collected specimens from 89 patients consenting to translational research, and performed Sanger sequencing for H3F3A, Illumina 450K BeadArray methylation profiling, and whole exome sequencing and RNA sequencing where possible. 7/89 patients (8%) harboured H3F3A G34R/V mutations, whilst 24/89 (27%) harboured H3F3A K27M, the latter reflecting a high proportion of the novel entity recognised in the 2016 WHO classification of diffuse midline glioma with H3K27M mutation. Both histone mutations conferred a significantly shorter progression-free (p=0.0104) and overall survival (p=0.00159). 450K methylation subtyping additionally identified a number of subgroups in histone wild-type cases. These included infrequent (4/86, 4.6%) cases with IDH1 mutation in older children, further categorised into astrocytic ATRX-mutant (n=3) or 1p19q co-deleted with TERT promoter mutation (n=1). 9/74, (12%) of cases were classified as biologically resembling pleomorphic xanthoastrocytoma (PXA) by methylation profiling, with 5/9 harbouring BRAF V600E mutations and epithelioid histology, and 3/9 NF1 mutation and giant cell features. Three cases had methylation profiles more closely resembling low grade gliomas, though were morphologically high grade, and harboured MAPK dysregulation in two cases, with the third part of an additional infant (&lt;3yrs) cohort. Finally, four cases had a mutational burden several orders of magnitude higher than the rest, with (2197-5332) somatic coding variants/sample reflecting a hypermutator phenotype. These data provide an important insight into the wide biological diversity of ‘HGG’ found in the paediatric age group and allow for a profound refinement of clinical trial interpretation.","abstract":"The HERBY trial was a phase-II open-label, randomised, multicentre trial evaluating bevacizumab in patients with newly-diagnosed non-brainstem high grade glioma (HGG) between the ages of 3-18yrs. 121 patients were randomised with 1yr event-free survival as the primary end-point. Confirmation of HGG diagnosis by  reference pathology was mandatory before randomisation, followed by review with five independent expert neuropathologists. We collected specimens from 89 patients consenting to translational research, and performed Sanger sequencing for H3F3A, Illumina 450K BeadArray methylation profiling, and whole exome sequencing and RNA sequencing where possible. 7/89 patients (8%) harboured H3F3A G34R/V mutations, whilst 24/89 (27%) harboured H3F3A K27M, the latter reflecting a high proportion of the novel entity recognised in the 2016 WHO classification of diffuse midline glioma with H3K27M mutation. Both histone mutations conferred a significantly shorter progression-free (p=0.0104) and overall survival (p=0.00159). 450K methylation subtyping additionally identified a number of subgroups in histone wild-type cases. These included infrequent (4/86, 4.6%) cases with IDH1 mutation in older children, further categorised into astrocytic ATRX-mutant (n=3) or 1p19q co-deleted with TERT promoter mutation (n=1). 9/74, (12%) of cases were classified as biologically resembling pleomorphic xanthoastrocytoma (PXA) by methylation profiling, with 5/9 harbouring BRAF V600E mutations and epithelioid histology, and 3/9 NF1 mutation and giant cell features. Three cases had methylation profiles more closely resembling low grade gliomas, though were morphologically high grade, and harboured MAPK dysregulation in two cases, with the third part of an additional infant (&lt;3yrs) cohort. Finally, four cases had a mutational burden several orders of magnitude higher than the rest, with (2197-5332) somatic coding variants/sample reflecting a hypermutator phenotype. These data provide an important insight into the wide biological diversity of ‘HGG’ found in the paediatric age group and allow for a profound refinement of clinical trial interpretation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-27T12:39:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002329","title":"Investigation_of_mutational_signatures_associated_with_DNMT3A_deficiency_","description":"Mutational signatures have been shown to be attributable to specific genetic contexts, such as mutations in DNA repair genes. DNMT3A is a DNA methyltransferase that helps maintain the DNA methylation pattern in a site-specific manner and may participate in DNA repair or the stress response. We have identified an adult individual who is a germline mosaic for a DNMT3A mutation. We have obtained clonal lymphoblastoid cells (LCLs) from the subject representing both WT and mutant lines grown in the same individual for &gt;50 years. These clones represent a unique opportunity to examine the mutational impact of the DNMT3A mutation in a well-controlled setting. Our goal is to perform WGS on whole blood, representing the pool, as well as several WT and several mutant clones, in order to investigate the contribution of DNMT3A to mutation rates and signatures.","abstract":"Mutational signatures have been shown to be attributable to specific genetic contexts, such as mutations in DNA repair genes. DNMT3A is a DNA methyltransferase that helps maintain the DNA methylation pattern in a site-specific manner and may participate in DNA repair or the stress response. We have identified an adult individual who is a germline mosaic for a DNMT3A mutation. We have obtained clonal lymphoblastoid cells (LCLs) from the subject representing both WT and mutant lines grown in the same individual for &gt;50 years. These clones represent a unique opportunity to examine the mutational impact of the DNMT3A mutation in a well-controlled setting. Our goal is to perform WGS on whole blood, representing the pool, as well as several WT and several mutant clones, in order to investigate the contribution of DNMT3A to mutation rates and signatures.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-02-27T15:17:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002330","title":"Germline mutations on the histone H4 core cause a developmental syndrome by affecting DNA damage response and cell cycle control","description":"Covalent modifications of histone N-tails have an established role in chromatin-based processes such as DNA replication, transcription and repair1. Loss of these modifications, whether due to mutations in genes belonging to histone tail-modifying complexes or directly affecting the histone tail, cause developmental disorders2-5 or play a role in tumorigenesis6. Despite this knowledge, however, very little is known about the function of modifications affecting the histone core. Here we report monoallelic missense mutations affecting Lysine 91 in the histone H4 core (H4K91) in three individuals with a syndrome of growth delay, microcephaly and intellectual disability. Expression of the H4 mutants in zebrafish embryos recapitulate the developmental anomalies seen in the patients. We show that the H4 mutations cause genomic instability, resulting in increased apoptosis and cell cycle progression anomalies during early development. Mechanistically, our findings indicate an important role for the ubiquitination of H4K91 in genomic stability during embryonic development.","abstract":"Covalent modifications of histone N-tails have an established role in chromatin-based processes such as DNA replication, transcription and repair1. Loss of these modifications, whether due to mutations in genes belonging to histone tail-modifying complexes or directly affecting the histone tail, cause developmental disorders2-5 or play a role in tumorigenesis6. Despite this knowledge, however, very little is known about the function of modifications affecting the histone core. Here we report monoallelic missense mutations affecting Lysine 91 in the histone H4 core (H4K91) in three individuals with a syndrome of growth delay, microcephaly and intellectual disability. Expression of the H4 mutants in zebrafish embryos recapitulate the developmental anomalies seen in the patients. We show that the H4 mutations cause genomic instability, resulting in increased apoptosis and cell cycle progression anomalies during early development. Mechanistically, our findings indicate an important role for the ubiquitination of H4K91 in genomic stability during embryonic development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002331","title":"160 WES and 25 WGS for HBV related HCC, and 15 WES for ICC belongs LICA-CN.","description":"160 WES and 25 WGS for HBV related HCC, and 15 WES for ICC belongs LICA-CN.","abstract":"160 WES and 25 WGS for HBV related HCC, and 15 WES for ICC belongs LICA-CN.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-01T02:10:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002332","title":"HuiPSDM_and_Mtb_","description":"Mycobacterium tuberculosis is a successive pathogen in part due to its ability to establish primary infection in host macrophages, thereby subverting the normal immune response.  M.tb had been very difficult to genetically manipulate until pioneering developments in the area of phage mediated homologous recombineering technology were  established by our lab and culminated in a library of mutant bacteria.  In an effort to more thoroughly study the interaction between host and microbe, we propose to establish a new in vitro infection model using macrophages derived from induced pluripotent stem cells (iPS cells).  iPS derived macrophages hold much promise as a new model system in that they are more like a host primary cell, the cell number is limitless and complete gene deletions in these human cells can be achieved. The use of iPS derived macrophage parental lines and subsequent gene knock-outs in conjunction with a library of M.tb mutants will provide us with keen insight into this pathogen-host interaction to be able to develop a better vaccine and new drug target candidates.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Our study goals and objectives are outlined generally in 3 Aims:\n1) Characterize the molecular host/pathogen interactions leading to impaired survival of specific M.tb mutants \n2) The use of iPS cell lines impaired in critical defense mechanisms will help identify pathways involved in intracellular killing of M.tb\n3) Development of a high throughput method to identify new M.tb mutants defective in immune evasion and survival","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002333","title":"Mapping and phasing of structural variation in patient genomes using nanopore sequencing","description":"We whole genome sequence 2 patients with congenital abnormalities and known complex de novo chromosomal rearrangements using the Nanopore MinION. We show how we can detect most previoulsy detected de novo rearrangements as well as uncover a few new ones. Furthermore, we perform genome-wide analyses showing the accuracy of SV detection and of phasing, using long reads. The files uploaded here are the whole genome Nanopore data for each of the two patients used, as well as the corresponding whole genome illumina data, used in our comparisons.","abstract":"We whole genome sequence 2 patients with congenital abnormalities and known complex de novo chromosomal rearrangements using the Nanopore MinION. We show how we can detect most previoulsy detected de novo rearrangements as well as uncover a few new ones. Furthermore, we perform genome-wide analyses showing the accuracy of SV detection and of phasing, using long reads. The files uploaded here are the whole genome Nanopore data for each of the two patients used, as well as the corresponding whole genome illumina data, used in our comparisons.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-01T15:38:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002334","title":"A GWAS in uveal melanoma identifies risk polymorphisms in the CLPTM1L locus.","description":"Uveal melanoma, a rare malignant tumor of the eye, is predominantly observed in populations of European ancestry. A genome-wide association study of 259 uveal melanoma patients compared to 401 controls all of European ancestry revealed a candidate locus at chromosome 5p15.33 (region rs421284: OR = 1.7, CI 1.43-2.05). This locus was replicated in an independent set of 276 cases and 184 controls. In addition, risk variants from this region were positively associated with higher expression of CLPTM1L. In conclusion, the CLPTM1L region contains risk alleles for uveal melanoma susceptibility, suggesting that CLPTM1L could play a role in uveal melanoma oncogenesis.","abstract":"Uveal melanoma, a rare malignant tumor of the eye, is predominantly observed in populations of European ancestry. A genome-wide association study of 259 uveal melanoma patients compared to 401 controls all of European ancestry revealed a candidate locus at chromosome 5p15.33 (region rs421284: OR = 1.7, CI 1.43-2.05). This locus was replicated in an independent set of 276 cases and 184 controls. In addition, risk variants from this region were positively associated with higher expression of CLPTM1L. In conclusion, the CLPTM1L region contains risk alleles for uveal melanoma susceptibility, suggesting that CLPTM1L could play a role in uveal melanoma oncogenesis.","study_type":"Other","pubmed_ids":[28781888],"external_links":null,"is_released":true,"released_date":"2017-03-01T16:31:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002335","title":"Drugging the catalytically inactive state of RET kinase in RET-rearranged tumors.","description":"Oncogenic fusion events have been identified in a broad range of tumors. Among them, RET rearrangements represent distinct and potentially druggable targets that are recurrently found in lung adenocarcinomas. We provide further evidence that current anti-RET drugs may not be potent enough to induce durable responses in such tumors. We report that potent inhibitors, such as AD80 or ponatinib, that stably bind in the DFG-out conformation of RET may overcome these limitations and selectively kill RET-rearranged tumors. Using chemical genomics in conjunction with phosphoproteomic analyses in RET-rearranged cells, we identify the CCDC6-RETI788N mutation and drug-induced mitogen-activated protein kinase pathway reactivation as possible mechanisms by which tumors may escape the activity of RET inhibitors. Our data provide mechanistic insight into the druggability of RET kinase fusions that may be of help for the development of effective therapies targeting such tumors.","abstract":"Oncogenic fusion events have been identified in a broad range of tumors. Among them, RET rearrangements represent distinct and potentially druggable targets that are recurrently found in lung adenocarcinomas. We provide further evidence that current anti-RET drugs may not be potent enough to induce durable responses in such tumors. We report that potent inhibitors, such as AD80 or ponatinib, that stably bind in the DFG-out conformation of RET may overcome these limitations and selectively kill RET-rearranged tumors. Using chemical genomics in conjunction with phosphoproteomic analyses in RET-rearranged cells, we identify the CCDC6-RETI788N mutation and drug-induced mitogen-activated protein kinase pathway reactivation as possible mechanisms by which tumors may escape the activity of RET inhibitors. Our data provide mechanistic insight into the druggability of RET kinase fusions that may be of help for the development of effective therapies targeting such tumors.","study_type":"Other","pubmed_ids":[28615362],"external_links":null,"is_released":true,"released_date":"2017-03-02T11:18:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002336","title":"UK renal cancer samples genotyped on Illumina OmniExpress BeadChip","description":"Renal cell carcinoma (RCC) cases comprised adult patients with histologically proven RCC were collected through two sources within the UK. First, 856 cases from SORCE, a MRC collection of surgically treated RCC cases ascertained through UK clinical oncology centres. Second, 189 RCC cases collected through the ICR and Royal Marsden NHS Hospitals Trust. Cases included 590 clear cell carcinomas (CCCs), 42 papillary carcinomas (PCs), 33 chromophobe carcinomas (CCs) and 19 mixed or other histological subtypes. DNA was extracted from EDTA-venous blood samples using the conventional methods and quantified using PicoGreen (Invitrogen). Cases were genotyped using the Human OmniExpress-12 BeadChip according to the manufacturer's recommendations (Illumina Inc, San Diego, CA, USA). After strict QC, 944 cases were retained. Data provided in plink format.\n\nControls used were data from the Wellcome Trust Case Control Consortium 2 (WTCCC2) 1958 birth cohort and the UK Blood Service Control Group (available as EGAS00000000028).","abstract":"Renal cell carcinoma (RCC) cases comprised adult patients with histologically proven RCC were collected through two sources within the UK. First, 856 cases from SORCE, a MRC collection of surgically treated RCC cases ascertained through UK clinical oncology centres. Second, 189 RCC cases collected through the ICR and Royal Marsden NHS Hospitals Trust. Cases included 590 clear cell carcinomas (CCCs), 42 papillary carcinomas (PCs), 33 chromophobe carcinomas (CCs) and 19 mixed or other histological subtypes. DNA was extracted from EDTA-venous blood samples using the conventional methods and quantified using PicoGreen (Invitrogen). Cases were genotyped using the Human OmniExpress-12 BeadChip according to the manufacturer's recommendations (Illumina Inc, San Diego, CA, USA). After strict QC, 944 cases were retained. Data provided in plink format.\n\nControls used were data from the Wellcome Trust Case Control Consortium 2 (WTCCC2) 1958 birth cohort and the UK Blood Service Control Group (available as EGAS00000000028).","study_type":"Other","pubmed_ids":[23184150],"external_links":null,"is_released":true,"released_date":"2017-03-02T19:52:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002337","title":"Poly(A) RNA sequencing of hepatocellular carcinoma tumors and their matched noncancerous liver tissues","description":"Background &amp; Aims: The differentiation of distinct multifocal hepatocellular carcinoma (HCC): multicentric disease vs. intrahepatic metastases, in which the management and prognosis varies substantively, remains problematic. We aim to stratify multifocal HCC and identify novel diagnostic and prognostic biomarkers by performing whole genome and transcriptome sequencing, as part of a multi-omics strategy Methods: A complete collection of tumour and somatic specimens (intrahepatic HCC lesions, matched non-cancerous liver tissue and blood) were obtained from representative patientswith multifocal HCC exhibiting two distinct postsurgical courses. Whole-genome and transcriptome sequencing with genotyping were performed for each tissue specimen to con-trast genomic alterations, including hepatitis B virus integrations, somatic mutations, copy number variations, and structural variations. We then constructed a phylogenetic tree to visualise individual tumour evolution and performed functional enrichment analyses on select differentially expressed genes to elucidate biological processes involved in multifocal HCC development. Multi-omics data were integrated with detailed clinicopathological information to identify HCC biomarkers, which were further validated using a large cohort of HCC patients (n = 174).Results: The multi-omics profiling and tumour biomarkers could successfully distinguish the two multifocal HCC types, while accurately predicting clonality and aggressiveness. The dual specificity protein kinase TTK, which is a key mitotic checkpoint regulator with links to p53 signaling, was further shown to be a promising overall prognostic marker for HCC in the large patient cohort.Conclusions: Comprehensive multi-omics characterisation of multifocal tumour evolution may improve clinical decision-making, facilitate personalised medicine, and expedite identification of novel biomarkers and therapeutic targets in HCC.","abstract":"Background &amp; Aims: The differentiation of distinct multifocal hepatocellular carcinoma (HCC): multicentric disease vs. intrahepatic metastases, in which the management and prognosis varies substantively, remains problematic. We aim to stratify multifocal HCC and identify novel diagnostic and prognostic biomarkers by performing whole genome and transcriptome sequencing, as part of a multi-omics strategy Methods: A complete collection of tumour and somatic specimens (intrahepatic HCC lesions, matched non-cancerous liver tissue and blood) were obtained from representative patientswith multifocal HCC exhibiting two distinct postsurgical courses. Whole-genome and transcriptome sequencing with genotyping were performed for each tissue specimen to con-trast genomic alterations, including hepatitis B virus integrations, somatic mutations, copy number variations, and structural variations. We then constructed a phylogenetic tree to visualise individual tumour evolution and performed functional enrichment analyses on select differentially expressed genes to elucidate biological processes involved in multifocal HCC development. Multi-omics data were integrated with detailed clinicopathological information to identify HCC biomarkers, which were further validated using a large cohort of HCC patients (n = 174).Results: The multi-omics profiling and tumour biomarkers could successfully distinguish the two multifocal HCC types, while accurately predicting clonality and aggressiveness. The dual specificity protein kinase TTK, which is a key mitotic checkpoint regulator with links to p53 signaling, was further shown to be a promising overall prognostic marker for HCC in the large patient cohort.Conclusions: Comprehensive multi-omics characterisation of multifocal tumour evolution may improve clinical decision-making, facilitate personalised medicine, and expedite identification of novel biomarkers and therapeutic targets in HCC.","study_type":"Other","pubmed_ids":[24859455],"external_links":null,"is_released":true,"released_date":"2017-03-03T13:56:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002338","title":"whole genome sequence data of multifocal hepatocellular carcinoma","description":"Background &amp; Aims: The differentiation of distinct multifocal hepatocellular carcinoma (HCC): multicentric disease vs. intrahepatic metastases, in which the management and prognosis varies substantively, remains problematic. We aim to stratify multifocal HCC and identify novel diagnostic and prognostic biomarkers by performing whole genome and transcriptome sequencing, as part of a multi-omics strategy Methods: A complete collection of tumour and somatic specimens (intrahepatic HCC lesions, matched non-cancerous liver tissue and blood) were obtained from representative patientswith multifocal HCC exhibiting two distinct postsurgical courses. Whole-genome and transcriptome sequencing with genotyping were performed for each tissue specimen to con-trast genomic alterations, including hepatitis B virus integrations, somatic mutations, copy number variations, and structural variations. We then constructed a phylogenetic tree to visualise individual tumour evolution and performed functional enrichment analyses on select differentially expressed genes to elucidate biological processes involved in multifocal HCC development. Multi-omics data were integrated with detailed clinicopathological information to identify HCC biomarkers, which were further validated using a large cohort of HCC patients (n = 174).Results: The multi-omics pro?ling and tumour biomarkers could successfully distinguish the two multifocal HCC types, while accurately predicting clonality and aggressiveness. The dual speci?city protein kinase TTK, which is a key mitotic checkpoint regulator with links to p53 signaling, was further shown to be a promising overall prognostic marker for HCC in the large patient cohort.Conclusions: Comprehensive multi-omics characterisation of multifocal tumour evolution may improve clinical decision-making, facilitate personalised medicine, and expedite identi?cation of novel biomarkers and therapeutic targets in HCC.","abstract":"Background &amp; Aims: The differentiation of distinct multifocal hepatocellular carcinoma (HCC): multicentric disease vs. intrahepatic metastases, in which the management and prognosis varies substantively, remains problematic. We aim to stratify multifocal HCC and identify novel diagnostic and prognostic biomarkers by performing whole genome and transcriptome sequencing, as part of a multi-omics strategy Methods: A complete collection of tumour and somatic specimens (intrahepatic HCC lesions, matched non-cancerous liver tissue and blood) were obtained from representative patientswith multifocal HCC exhibiting two distinct postsurgical courses. Whole-genome and transcriptome sequencing with genotyping were performed for each tissue specimen to con-trast genomic alterations, including hepatitis B virus integrations, somatic mutations, copy number variations, and structural variations. We then constructed a phylogenetic tree to visualise individual tumour evolution and performed functional enrichment analyses on select differentially expressed genes to elucidate biological processes involved in multifocal HCC development. Multi-omics data were integrated with detailed clinicopathological information to identify HCC biomarkers, which were further validated using a large cohort of HCC patients (n = 174).Results: The multi-omics pro?ling and tumour biomarkers could successfully distinguish the two multifocal HCC types, while accurately predicting clonality and aggressiveness. The dual speci?city protein kinase TTK, which is a key mitotic checkpoint regulator with links to p53 signaling, was further shown to be a promising overall prognostic marker for HCC in the large patient cohort.Conclusions: Comprehensive multi-omics characterisation of multifocal tumour evolution may improve clinical decision-making, facilitate personalised medicine, and expedite identi?cation of novel biomarkers and therapeutic targets in HCC.","study_type":"Other","pubmed_ids":[24859455],"external_links":null,"is_released":true,"released_date":"2017-03-03T14:47:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002339","title":"Whole exome sequencing in cardiovascular patients","description":"Whole exome sequencing in cardiovascular patients that include arrhythmia and cardiomyopathy patients of different entities.\n\nPUBMED 28219978:\nIn a patient with right ventricular outflow tract (RVOT) tachycardia we identified a heterozygous point mutation in the selectivity filter of the stretch-activated K2P potassium channel TREK-1 (KCNK2 or K2P2.1). This mutation introduces abnormal sodium permeability to TREK-1 In addition, mutant channels exhibit a hypersensitivity to stretch-activation, suggesting that the selectivity filter is directly involved in stretch-induced activation and desensitization. Increased sodium permeability and stretch-sensitivity of mutant TREK-1 channels may trigger arrhythmias in areas of the heart with high physical strain such as the RVOT. We present a pharmacological strategy to rescue the selectivity defect of the TREK-1 pore. Our findings provide important insights for future studies of K2P channel stretch-activation and the role of TREK-1 in mechano-electrical feedback in the heart.","abstract":"Whole exome sequencing in cardiovascular patients that include arrhythmia and cardiomyopathy patients of different entities.\n\nPUBMED 28219978:\nIn a patient with right ventricular outflow tract (RVOT) tachycardia we identified a heterozygous point mutation in the selectivity filter of the stretch-activated K2P potassium channel TREK-1 (KCNK2 or K2P2.1). This mutation introduces abnormal sodium permeability to TREK-1 In addition, mutant channels exhibit a hypersensitivity to stretch-activation, suggesting that the selectivity filter is directly involved in stretch-induced activation and desensitization. Increased sodium permeability and stretch-sensitivity of mutant TREK-1 channels may trigger arrhythmias in areas of the heart with high physical strain such as the RVOT. We present a pharmacological strategy to rescue the selectivity defect of the TREK-1 pore. Our findings provide important insights for future studies of K2P channel stretch-activation and the role of TREK-1 in mechano-electrical feedback in the heart.","study_type":"Other","pubmed_ids":[28219978],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002340","title":"Somatic_mutation_and_clonal_evolution_in_premalignant_lung_disease","description":"In this study we aim to characterise the landscape of mutation and clonal selection in normal lung and premalignant lung disease. The study combines targeted sequencing and whole-genome sequencing of microbiopsies of lung and bronchial epithelium. The range of patients studied will include healthy individuals, both smokers and non-smokers, and patients with premalignant lung disease.","abstract":"In this study we aim to characterise the landscape of mutation and clonal selection in normal lung and premalignant lung disease. The study combines targeted sequencing and whole-genome sequencing of microbiopsies of lung and bronchial epithelium. The range of patients studied will include healthy individuals, both smokers and non-smokers, and patients with premalignant lung disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-06T11:18:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002341","title":"160 WES and 25 WGS for HBV related HCC, and 15 WES for ICC belongs LICA-CN..","description":"ega-STUDY-NCPSB-04-01-2016-12:20:53:010-481","abstract":"ega-STUDY-NCPSB-04-01-2016-12:20:53:010-481","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002342","title":"obsolete--Empty Study Accidentally Created","description":"Need to be filled later","abstract":"Need to be filled later","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002343","title":"Copy number profiling of putative cancer stem from pleural effusion aspirates from breast cancer patients","description":"A common symptom during late stage breast cancer disease is pleural effusion, which is related to poor prognosis. In pleural effusions malignant cells can be detected, which indicates a metastatic spread from the primary tumor site. Beside the usefulness for investigation of the metastatic process, it has been a source to isolate cells with putative cancer stem cell (CSC) properties. For this study, pleural effusion aspirate from 25 metastatic breast cancer patients were processed to establish in vitro culture. Patient-derived aspirates were cultured under sphere forming conditions and isolated primary cultures were sorted for cancer stem cell populations ALDH1+ and CD44+CD24-/low and sphere forming efficiency of CSC and non-CSC subpopulation was determined. Unsorted cells had a higher potential to form spheres compared to CSC subpopulations. Subsequently, DNA was isolated from pleural effusions before and after cell sorting, to compare their copy number profiles generated by low-coverage whole genome sequencing to DNA from FFPE primary tumors or bone metastasis. Unbalanced profiles could be detected in four pleural samples before sorting, in two ALDH1+ sorted samples, in one CD44+CD24-/low and in all control samples.  Additionally, spheroid culture from one pleural sample could be passaged on and was characterized. Therefore, pleural effusions are an appropriate media for enrichment of putative CSC. However, low-coverage sequencing is difficult due to low quantities of abnormal cells compared to normal cells.","abstract":"A common symptom during late stage breast cancer disease is pleural effusion, which is related to poor prognosis. In pleural effusions malignant cells can be detected, which indicates a metastatic spread from the primary tumor site. Beside the usefulness for investigation of the metastatic process, it has been a source to isolate cells with putative cancer stem cell (CSC) properties. For this study, pleural effusion aspirate from 25 metastatic breast cancer patients were processed to establish in vitro culture. Patient-derived aspirates were cultured under sphere forming conditions and isolated primary cultures were sorted for cancer stem cell populations ALDH1+ and CD44+CD24-/low and sphere forming efficiency of CSC and non-CSC subpopulation was determined. Unsorted cells had a higher potential to form spheres compared to CSC subpopulations. Subsequently, DNA was isolated from pleural effusions before and after cell sorting, to compare their copy number profiles generated by low-coverage whole genome sequencing to DNA from FFPE primary tumors or bone metastasis. Unbalanced profiles could be detected in four pleural samples before sorting, in two ALDH1+ sorted samples, in one CD44+CD24-/low and in all control samples.  Additionally, spheroid culture from one pleural sample could be passaged on and was characterized. Therefore, pleural effusions are an appropriate media for enrichment of putative CSC. However, low-coverage sequencing is difficult due to low quantities of abnormal cells compared to normal cells.","study_type":"Other","pubmed_ids":[28423035],"external_links":null,"is_released":true,"released_date":"2017-03-07T16:21:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002344","title":"Whole-Genome Sequencing Suggests Schizophrenia Risk Mechanisms in Humans with 22q11.2 Deletion Syndrome","description":"Chromosome 22q11.2 microdeletions impart a high but incomplete risk for schizophrenia. Possible mechanisms include genome-wide effects of DGCR8 haploinsufficiency. In a proof-of-principle study to assess the power of this model, we used high-quality, whole-genome sequencing of nine individuals with 22q11.2 deletions and extreme phenotypes (schizophrenia, or no psychotic disorder at age &gt;50 years). The schizophrenia group had a greater burden of rare, damaging variants impacting protein-coding neurofunctional genes, including genes involved in neuron projection (nominal P = 0.02, joint burden of three variant types). Variants in the intact 22q11.2 region were not major contributors. Restricting to genes affected by a DGCR8 mechanism tended to amplify between-group differences. Damaging variants in highly conserved long intergenic noncoding RNA genes also were enriched in the schizophrenia group (nominal P = 0.04). The findings support the 22q11.2 deletion model as a threshold-lowering first hit for schizophrenia risk. If applied to a larger and thus better-powered cohort, this appears to be a promising approach to identify genome-wide rare variants in coding and noncoding sequence that perturb gene networks relevant to idiopathic schizophrenia. Similarly designed studies exploiting genetic models may prove useful to help delineate the genetic architecture of other complex phenotypes.","abstract":"Chromosome 22q11.2 microdeletions impart a high but incomplete risk for schizophrenia. Possible mechanisms include genome-wide effects of DGCR8 haploinsufficiency. In a proof-of-principle study to assess the power of this model, we used high-quality, whole-genome sequencing of nine individuals with 22q11.2 deletions and extreme phenotypes (schizophrenia, or no psychotic disorder at age &gt;50 years). The schizophrenia group had a greater burden of rare, damaging variants impacting protein-coding neurofunctional genes, including genes involved in neuron projection (nominal P = 0.02, joint burden of three variant types). Variants in the intact 22q11.2 region were not major contributors. Restricting to genes affected by a DGCR8 mechanism tended to amplify between-group differences. Damaging variants in highly conserved long intergenic noncoding RNA genes also were enriched in the schizophrenia group (nominal P = 0.04). The findings support the 22q11.2 deletion model as a threshold-lowering first hit for schizophrenia risk. If applied to a larger and thus better-powered cohort, this appears to be a promising approach to identify genome-wide rare variants in coding and noncoding sequence that perturb gene networks relevant to idiopathic schizophrenia. Similarly designed studies exploiting genetic models may prove useful to help delineate the genetic architecture of other complex phenotypes.","study_type":"Other","pubmed_ids":[26384369],"external_links":null,"is_released":true,"released_date":"2017-03-07T22:32:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002345","title":"South_American_genome_sequences","description":"Whole genome sequences of Native Americans from four different countries in South America for studies of their genetic history.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Whole genome sequences of Native Americans from four different countries in South America for studies of their genetic history.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002346","title":"Transcriptome sequencing of myelodysplasia","description":"Transcriptome sequencing was performed on 214 patients with myelodysplasia in this study. RNA was obtained from bone marrow CD34+ cells (n=100) and/or bone marrow mononuclear cells (n=165). Transcriptome sequencing was performed for both cell fractions in 51 patients. We also studied bone marrow CD34+ cells and bone marrow mononuclear cells obtained from three healthy adults each.","abstract":"Transcriptome sequencing was performed on 214 patients with myelodysplasia in this study. RNA was obtained from bone marrow CD34+ cells (n=100) and/or bone marrow mononuclear cells (n=165). Transcriptome sequencing was performed for both cell fractions in 51 patients. We also studied bone marrow CD34+ cells and bone marrow mononuclear cells obtained from three healthy adults each.","study_type":"Other","pubmed_ids":[29097382],"external_links":null,"is_released":true,"released_date":"2017-03-09T02:24:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002347","title":"Edinburgh_Naevi_Cohort","description":"In this project we have sequenced the exome of skin moles (melanocytic naevi) and also normal skin from young and old people. We are interested in looking at the clonality of these lesions and the burden of UV mutations","abstract":"In this project we have sequenced the exome of skin moles (melanocytic naevi) and also normal skin from young and old people. We are interested in looking at the clonality of these lesions and the burden of UV mutations","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-09T10:08:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002348","title":"Mutational_hotspot_analysis_for_detection_of_ongoing_mutagensis","description":"Signatures 2 and 13 reflect the second most prevalent mutational process operative in human cancer. Based on the similarity of the mutation types at the specific sequence context that constitute these signatures, they are speculated to stem from the aberrant activity of the APOBEC family of deaminases. We recently employed human cancer cell lines branded with signatures 2 and 13 to study activity of the mutational process generating them and found that only a subset continues to accumulate mutations over a period of time in culture. \n\nThe over-arching aim of this project will be to expand the currently scarce repertoire of known human cancer cell lines with the on-going mutagenic activity attributed to two signatures described. Our previous experiments suggest that private mutations found across individual cells from a heterogeneous cell line population may identify samples with mutational processes that are still operative. Here, we will attempt to replace whole-exome sequencing to detect private mutations forming Signature 2 and 13 patterns, with a deep sequencing of Signature 2 and 13 hotspots recently identified in BASIS project. These will be amplified from cell lines that are hypermutators for signatures 2 and 13","abstract":"Signatures 2 and 13 reflect the second most prevalent mutational process operative in human cancer. Based on the similarity of the mutation types at the specific sequence context that constitute these signatures, they are speculated to stem from the aberrant activity of the APOBEC family of deaminases. We recently employed human cancer cell lines branded with signatures 2 and 13 to study activity of the mutational process generating them and found that only a subset continues to accumulate mutations over a period of time in culture. \n\nThe over-arching aim of this project will be to expand the currently scarce repertoire of known human cancer cell lines with the on-going mutagenic activity attributed to two signatures described. Our previous experiments suggest that private mutations found across individual cells from a heterogeneous cell line population may identify samples with mutational processes that are still operative. Here, we will attempt to replace whole-exome sequencing to detect private mutations forming Signature 2 and 13 patterns, with a deep sequencing of Signature 2 and 13 hotspots recently identified in BASIS project. These will be amplified from cell lines that are hypermutators for signatures 2 and 13","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002349","title":"Single_cell_sequencing_of_oesophageal_cancer","description":"Following tumor tissue disaggregation, single cells were sorted in 96 well-plates and subjected to G&amp;T-seq, a method for sequencing the genome and transcriptome of single cells in parallel. The genomes will be low coverage sequenced to enable DNA copy number profiling and reconstructing the phylogeny of the cells, disclosing the intratumour subclonal genetic architecture and the temporal acquisition of somatic DNA copy number alterations. By sequencing the RNA of the same single cells, we will be able to discover cell type(s) and subpopulations of transcriptional cancer cell states. This information can then be layered on top of the DNA-derived cell lineage tree, revealing whether particular cancer cell states are confined to particular genetically distinct subclones, or whether cancer cell states are scattered across the cell lineage tree.","abstract":"Following tumor tissue disaggregation, single cells were sorted in 96 well-plates and subjected to G&amp;T-seq, a method for sequencing the genome and transcriptome of single cells in parallel. The genomes will be low coverage sequenced to enable DNA copy number profiling and reconstructing the phylogeny of the cells, disclosing the intratumour subclonal genetic architecture and the temporal acquisition of somatic DNA copy number alterations. By sequencing the RNA of the same single cells, we will be able to discover cell type(s) and subpopulations of transcriptional cancer cell states. This information can then be layered on top of the DNA-derived cell lineage tree, revealing whether particular cancer cell states are confined to particular genetically distinct subclones, or whether cancer cell states are scattered across the cell lineage tree.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002350","title":"Clonal_haemopoiesis_in_survivors_of_childhood_leukaemia","description":"We have evaluated blood DNA samples from childhood leukaemia survivors for evidence of clonal haematopoiesis, a possible risk factor for therapy-related AML, using barcoded multiplex PCR for leukaemia-associated mutations.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Therapy-related acute myeloid leukaemia (tAML) is a significant cause of non-relapse mortality amongst survivors of childhood cancers. Several recent studies have demonstrated that age-related clonal haematopoiesis due to leukaemia-associated mutations is a common phenomenon and a strong risk factor for developing AML. tAML is characterised by a high frequency of TP53 mutations, previously attributed to DNA damage caused by cytotoxic cancer treatments. However, recent work has demonstrated that chemotherapy may instead select for rare TP53-mutated haematopoietic progenitors that predate cytotoxic exposure. These findings raise the possibility that a significant proportion of tAMLs that do not harbour a TP53 mutation (approx. 66%) may be traced to founder clones harbouring other initiating mutations that conferred a selective growth advantage during cancer treatment. This study uses a highly sensitive barcoded multiplex PCR assay followed by deep sequencing to investigate the frequency of clonal haematopoiesis due to ~20 common AML/MDS-associated mutations in survivors of childhood leukaemia. Understanding the clonal evolution of tAML could permit screening for patients with predisposing mutations and a tailored treatment and follow-up approach for those at highest risk of clonal evolution to tAML/tMDS.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002351","title":"Combination_Therapies_for_Personalised_Cancer_Medicine_in_EGFR_mutant_lung_cancer","description":"This study involves mutagenizing a range of different cell lines with ENU to identify those mutations which engender resistance to targeted treatment.","abstract":"In the last decade we have begun to move towards the use of targeted therapeutics in the clinic, often resulting in dramatic response rates in cancer patients. However, clinical experience has demonstrated time and time again that such responses are invariably followed by the development of drug resistance. Identification of the underlying mechanisms may enable us to reverse such resistance. Traditional methods of modelling this resistance in vitro can lead to a plethora of potential resistance mechanisms that can be difficult to decipher.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002352","title":"In this study, we performed exon sequencing (WXS) of 80 paired Brain cancer tumors and adjacent normal tissues to identify novel potential biomarkers. We extracted mutational signatures which induce somatic mutations . Our study covers a comprehensive genetic framework that can be used in clinical trials and treatment modalities in Brain cancer.","description":"In this study, we performed exon sequencing (WXS) of 80 paired Brain cancer tumors and adjacent normal tissues to identify novel potential biomarkers. We extracted mutational signatures which induce somatic mutations . Our study covers a comprehensive genetic framework that can be used in clinical trials and treatment modalities in Brain cancer.","abstract":"In this study, we performed exon sequencing (WXS) of 80 paired Brain cancer tumors and adjacent normal tissues to identify novel potential biomarkers. We extracted mutational signatures which induce somatic mutations . Our study covers a comprehensive genetic framework that can be used in clinical trials and treatment modalities in Brain cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-10T07:33:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002353","title":"ctDNA_amplicon_sequencing_pilot","description":"Test of amplicon sequencing from ctDNA.","abstract":"Test of amplicon sequencing from ctDNA.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002354","title":"Low_depth_mapping_of_mutant_clones_in_human_oesophagus","description":"Human oesophageal tissue will be collected from post-mortem samples.  The epithelia will be separated from the underlying sub-mucosa and paraformaldehyde fixed.  Mapped 4mm2 biopsies will be excised from the epithelia and DNA extracted.  DNA will then be sent for low coverage whole exome sequencing.","abstract":"We are interested in the mutational burnden in normal human oesophageal epithelia.  We are in the process of analysing high depth targetted sequencing to examine small clones and clone sizes.  However we are also interested in seeing if other mutations not in our bait panel can drive clonal expansion.  Low depth sequencing shold allow us to pull out large clones and analyse their mutation pattern.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002355","title":"Genotyping_analysis_of_patients_with_POT1_mutation","description":"Using the CoreExome chip, the aim of this study is to genotype patient DNA samples","abstract":"Using the CoreExome chip, the aim of this study is to genotype patient DNA samples","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002356","title":"Recurrence_testing___Familial_melanoma","description":"The two most commonly mutated genes in familial melanoma are CDKN2A and CDK4 which account for around 40% of the familial cases of the disease. We have sequenced the exomes of 41 individuals from 23 pedigrees that do not carry mutations in either of these genes in an attempt to discover new melanoma susceptibility loci. In this experiment we follow-up this analysis by sequencing 96 individuals for a selected set of genes.","abstract":"The two most commonly mutated genes in familial melanoma are CDKN2A and CDK4 which account for around 40% of the familial cases of the disease. We have sequenced the exomes of 41 individuals from 23 pedigrees that do not carry mutations in either of these genes in an attempt to discover new melanoma susceptibility loci. In this experiment we follow-up this analysis by sequencing 96 individuals for a selected set of genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002357","title":"Mutational_consequences_of_in_vitro_radiation_exposure_in_a_laboratory_setting","description":"This project is to study the mutational consequences of in vitro radiation exposure in a laboratory setting. Initially looking, using genotyping arrays, to find cell lines that have relatively numerous copy number changes to take forward for whole exome sequencing.","abstract":"This project is to study the mutational consequences of in vitro radiation exposure in a laboratory setting. Initially looking, using genotyping arrays, to find cell lines that have relatively numerous copy number changes to take forward for whole exome sequencing.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002358","title":"Cancer_Cell_Line_Amplicon_Resolution","description":"The central aim of the study is to resolve the genomic positions and linear structures of high copy number amplicons in cancer cell lines. This provides the basis for studying the epigenetic landscape and regulation of these amplicons","abstract":"The majority of human cancer genes identified to date are somatically rearranged in the small minority of human cancers comprising leukemias, lymphomas and soft tissue tumors. However, conventional strategies for characterizing rearrangements are laborious, low-throughput and have low sensitivity/resolution. We aim to use massively parallel paired end sequencing to explore the diversity of aberrant processes sculpting genomes, and to identify novel rearranged cancer genes and gene fusions that may be future therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002359","title":"Radiation_cancer_validation_study","description":"Validation of Whole genome sequencing will be performed on genomic DNA derived from radiotherapy induced sarcoma samples and matched normal DNA from the same patients. Next Generation sequencing will be performed on the resulting targeted capture libraries and mapped to build 37 of the human reference genome to confirm the identification of mutations found in the original sequncing.","abstract":"Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina massively parallel sequencing technology, we aim to sequence microRNAs plus the protein coding genome of a number of matched human Cancer/Normal samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002360","title":"In_Situ_Transcription_RNAseq","description":"Whole transcriptome sequencing of multifocal breast cancer regions.","abstract":"Whole transcriptome sequencing of multifocal breast cancer regions.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002361","title":"Wholegenome_Chromothripsis_Cell_Lines","description":"Whole-genome rearrangement screens on cells lines with chromothripsis to search for sub-telomeric rearrangements indicative of telomeric crisis and fusion.","abstract":"The mechanism of chromothripsis has so far been unclear, but some existing evidence suggests dicentric chromosomal structure may predispose to chromothripsis. Telomere shortening, crisis and the ensuing telomeric fusions generate dicentric chromosomes. In this study, we perform low-coverage rearrangement screens on cell lines with chromothripsis to search for sub-telomeric rearrangements indicative of past telomeric fusions.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002362","title":"ENU_mutagenesis_in_Melanoma","description":"The study will use a chemical mutagen to induce mutations in  population of BRAF mutant melanoma cells, these will undergo drug selection pressure and surviving clones will be analysed using two strategies\n 1) pooled and compared to ENU only treated cells \n 2) expanded and picked as individual clones and assessed for phenotype.","abstract":"To discover novel resistance causing mutations in BRAF mutant melanoma utilising the chemical mutagen ENU.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002363","title":"TERT_5__UTR_Screening_in_RCCs__QC_","description":"Validation screen aimed at confirming the findings of alterations in the TERT 5'UTR and translocations involving chromosomes 3p and 5q in renal cell carcionoma - sample QC and Fluidigm.","abstract":"Validation screen aimed at confirming the findings of alterations in the TERT 5'UTR and translocations involving chromosomes 3p and 5q in renal cell carcionoma - sample QC and Fluidigm.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002364","title":"Ongoing_mutagenesis_RNAseq","description":"One of the key questions to be explored is whether the biological processes generating specific mutational signatures continue to operate in the human cancer cell lines or simply reflect past mutagenic activity which is no longer operative. To address this question, we have extracted mutational signatures from 1,000 cancer cell lines of diverse cancer types. Several cell lines with mutational signatures of interest were selected, subcloned over a defined period of time and their genomes sequenced. The increased load of the mutations representative of a specific mutational signature within the genome of a subclone when compared to its parental clone was informative of the on-going mutational processes. To further study the recent observation that some of the clones belonging to a same cell line acquired differencet numbers of mutations over a set period of time, their RNA will be subjected to RNA-sequencing to study their differences.","abstract":"One of the key questions to be explored is whether the biological processes generating specific mutational signatures continue to operate in the human cancer cell lines or simply reflect past mutagenic activity which is no longer operative. To address this question, we have extracted mutational signatures from 1,000 cancer cell lines of diverse cancer types. Several cell lines with mutational signatures of interest were selected, subcloned over a defined period of time and their genomes sequenced. The increased load of the mutations representative of a specific mutational signature within the genome of a subclone when compared to its parental clone was informative of the on-going mutational processes. To further study the recent observation that some of the clones belonging to a same cell line acquired differencet numbers of mutations over a set period of time, their RNA will be subjected to RNA-sequencing to study their differences.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-10T15:04:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002365","title":"A GWAS in uveal melanoma identifies risk polymorphisms in the CLPTM1L locus.","description":"Uveal melanoma, a rare malignant tumor of the eye, is predominantly observed in populations of European ancestry. A genome-wide association study of 259 uveal melanoma patients compared to 401 controls all of European ancestry revealed a candidate locus at chromosome 5p15.33 (region rs421284: OR = 1.7, CI 1.43-2.05). This locus was replicated in an independent set of 276 cases and 184 controls. In addition, risk variants from this region were positively associated with higher expression of CLPTM1L. In conclusion, the CLPTM1L region contains risk alleles for uveal melanoma susceptibility, suggesting that CLPTM1L could play a role in uveal melanoma oncogenesis.","abstract":"Uveal melanoma, a rare malignant tumor of the eye, is predominantly observed in populations of European ancestry. A genome-wide association study of 259 uveal melanoma patients compared to 401 controls all of European ancestry revealed a candidate locus at chromosome 5p15.33 (region rs421284: OR = 1.7, CI 1.43-2.05). This locus was replicated in an independent set of 276 cases and 184 controls. In addition, risk variants from this region were positively associated with higher expression of CLPTM1L. In conclusion, the CLPTM1L region contains risk alleles for uveal melanoma susceptibility, suggesting that CLPTM1L could play a role in uveal melanoma oncogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002366","title":"CEHM","description":"Study of the genetic and epigenetic clonal evolution of blood cancers.","abstract":"Clonality is a universal feature of cancer, and genetic/epigenetic clonal diversity poses a serious challenge to therapy. All cancer treatments have the potential to select for resistant disease, and improved understanding cancer evolution will be essential for designing treatment protocols that avoid relapse. This study will investigate the preclinical and malignant clonal evolution of several types of haematological malignancy.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-10T16:50:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002367","title":"Prostate Cancer RNA Seq","description":null,"abstract":"Raw RNA Sequence data from the CPCGene Project.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002368","title":"HYPERMUTATION AND MALIGNANT PROGRESSION IN LOW-GRADE GLIOMA PATIENTS","description":"While patients with primary glioblastoma (GBM) have benefited from increased overall survival due to treatment with the alkylating chemotherapy temozolomide (TMZ), the benefit ofTMZ for patients with diffuse low-grade gliomas (LGG) remains unknown. To further explore the relationships among TMZ treatment, hypermutation and malignant progression, we studied tumor evolution in an expanded cohort of untreated and TMZ-treated patients by exome-sequencing of paired IDH1/2-mutant LGGs and their post-TMZ recurrences.  Together, these findings further our understanding of the molecular features and clinical behavior of hypermutated clones.","abstract":"While patients with primary glioblastoma (GBM) have benefited from increased overall survival due to treatment with the alkylating chemotherapy temozolomide (TMZ), the benefit ofTMZ for patients with diffuse low-grade gliomas (LGG) remains unknown. To further explore the relationships among TMZ treatment, hypermutation and malignant progression, we studied tumor evolution in an expanded cohort of untreated and TMZ-treated patients by exome-sequencing of paired IDH1/2-mutant LGGs and their post-TMZ recurrences.  Together, these findings further our understanding of the molecular features and clinical behavior of hypermutated clones.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-10T22:17:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002369","title":"Global_gene_expression_profiles_in_whole_blood_of_humans_during_infection_with_Salmonella_Typhi","description":"A human volunteer challenge model for typhoid fever has recently been established at the Oxford Biomedical Research Centre, University of Oxford. More than forty individuals have been infected with 1x10(4) CFU S. Typhi and the transcriptional response in peripheral blood of ten volunteers before infection and on development of fever or on day 14 id no fever was diagnosed has been determined using Illumina™ Human HT-12_V4 Beadchips (Illumina, San Diego, CA, USA). A strong transcriptional signature was associated with typhoid diagnosis.We propose to determine the peripheral blood trancriptional response at additional time points. Further we will detemrine th peripheral blood trancriptional response to vaccination with an established live oral typhoid vaccine Ty21a, a novel live oral vaccine and a placebo control.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"A human volunteer challenge model for typhoid fever has recently been established at the Oxford Biomedical Research Centre, University of Oxford. More than forty individuals have been infected with 1x10(4) CFU S. Typhi and the transcriptional response in peripheral blood of ten volunteers before infection and on development of fever or on day 14 id no fever was diagnosed has been determined using Illumina™ Human HT-12_V4 Beadchips (Illumina, San Diego, CA, USA). A strong transcriptional signature was associated with typhoid diagnosis.We propose to determine the peripheral blood trancriptional response at additional time points. Further we will determine th peripheral blood trancriptional response to vaccination with an established live oral typhoid vaccine Ty21a, a novel live oral vaccine and a placebo control.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002370","title":"Global_gene_expression_profiles_in_whole_blood_of_humans_during_infection_with_Salmonella_Typhi","description":"A human volunteer challenge model for typhoid fever has recently been established at the Oxford Biomedical Research Centre, University of Oxford. More than forty individuals have been infected with 1x10(4) CFU S. Typhi and the transcriptional response in peripheral blood of ten volunteers before infection and on development of fever or on day 14 id no fever was diagnosed has been determined using Illumina™ Human HT-12_V4 Beadchips (Illumina, San Diego, CA, USA). A strong transcriptional signature was associated with typhoid diagnosis.We propose to determine the peripheral blood trancriptional response at additional time points. Further we will detemrine th peripheral blood trancriptional response to vaccination with an established live oral typhoid vaccine Ty21a, a novel live oral vaccine and a placebo control.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"A human volunteer challenge model for typhoid fever has recently been established at the Oxford Biomedical Research Centre, University of Oxford. More than forty individuals have been infected with 1x10(4) CFU S. Typhi and the transcriptional response in peripheral blood of ten volunteers before infection and on development of fever or on day 14 id no fever was diagnosed has been determined using Illumina™ Human HT-12_V4 Beadchips (Illumina, San Diego, CA, USA). A strong transcriptional signature was associated with typhoid diagnosis.We propose to determine the peripheral blood trancriptional response at additional time points. Further we will determine th peripheral blood trancriptional response to vaccination with an established live oral typhoid vaccine Ty21a, a novel live oral vaccine and a placebo control.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002371","title":"Somatic_mutation_in_Primary_Sj_gren_s_Syndrome","description":"The overall objective is to test the hypothesis that PSS is caused by somatic mutation of immune regulatory or checkpoint genes in lymphoid cells.","abstract":"Autoimmune diseases affect 5% of the population and cause a wide range of painful disabilities that affect quality of life and may lead to life-threatening complications and early death.  In all these conditions, the immune system becomes hyperactive and damages tissues of the body including the joints, skin, mucous membranes, glands and vital organs.  In health, immune responses are closely regulated so that auto-immunity dose not occur.  Although research has identified many new ways to suppress auto-immunity, the reason why the immune system escapes from control in the first place, is completely unknown.\n\nThrough this research we are testing a new hypothesis that could explain why immune responses no longer respond to regulation in autoimmune disease.  Throughout life, tissues of the body accumulate genetic mutations due to random errors in copying the DNA when cells divide.  These mutations are known as 'somatic' mutations to indicate that they occur within an individual's lifetime and are not inherited from one generation to the next.  Somatic mutations are the cause of cancer and may play an important role in many chronic and age-related diseases.  Our research aims to test whether somatic mutations also cause autoimmunity.  The idea is that genes that control immune responses may become defective so that immune cells escape from normal regulatory signals.  There is evidence to support this idea from rare patients with inherited mutations that develop autoimmunity at a young age.  We also know that patients with autoimmunity, especially those with primary Sjogren's syndrome are at risk of developing lymphoma, a cancer of the immune system that involves exactly the same cells that cause autoimmunity.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002372","title":"Evolution_of_the_cancer_epigenome_in_myeloproliferative_neoplasms_2","description":"Whole genome sequencing and bisulphite sequencing of haematopoietic colonies","abstract":"Cancer clones emerge and evolve through somatic mutation acquisition and Darwinian selection, but the dynamics of clonal evolution remain poorly understood and predicting disease progression remains a real challenge. Genes that regulate the epigenome are clearly important targets of mutations in cancer, but the mechanisms by which they drive tumour evolution remain unknown.\nThe myeloproliferative neoplasms (MPN) are haematopoietic disorders that represent an excellent model to study genomic and epigenomic evolution in human cancers: (i) They are genetically well-defined with disease driving mutations in JAK2, CALR (which I described in 2013) or MPL, present alongside mutations in epigenetic regulators, such as, DNMT3A. (ii) Disease can be either stable, or progress to leukaemia or myelofibrosis, providing the opportunity to study the basis for these evolutionary differences, and (iii) Primary cells can be serially sampled at the clonal level enabling inter- and intra-clonal studies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-13T14:58:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002373","title":"Impact of RB1 genotype on the mutational landscape and evolution of retinoblastoma","description":"Retinoblastoma is the most common eye tumour in children, and despite being highly curable, the primary treatment courses (enucleation or chemotherapy) severely impact patient well being and must be carefully chosen. Although retinoblastoma was one of the first tumours to provide clear insight into the genetic basis of cancer, its genomic underpinnings have not yet been fully resolved. The loss of tumour-suppressor gene RB is a main driving event in both hereditary and sporadic retinoblastoma, but this event alone cannot initiate a malignant tumour. A rare subset of retinoblastomas carry wildtype RB, and instead harbour amplification of the MYCN oncogene. However, not all RB1++ tumours carry a MYCN amplification, suggesting other mutations may contribute to pathogenicity. Here, we compare the mutational landscape and evolution of RB1++, RB1+-, and RB1-- retinoblastomas to explore how the presence or absence of a key driver event shapes somatic evolution of the genome. We find CNAs are largely consistent between RB1 genotype groups, but show clear evidence of heterogeneity among RB1-- patients, and uncover novel potential drivers within common chromosomal aberrations including NBAS, CENPF,DFFB, and CHDL1. In contrast, we observe differences in the frequency of coding poiunt mutations among RB1 genoytpe groups for genes including MUC4, EN1, YWAB, and PHF20l1 and further show mutational signatures differ between these groups. We also observe extensive structural rearrangements in both RB1+- and RB1++ samples, as well as evidence of chromothripsis in all samples, often enveloping RB or MYCN, highlighting the general importance of structural variants in retinoblastoma. Finally, we show subclonality is common among retinoblastoma samples, and find copy number aberrations, including RB1 loss and MYCN amplification, occur later in tumour evolution than point mutations. These findings suggest tumours with different RB1 genotypes can experience different mutational processes early in their evolution that manifest mainly through point mutations, but ultimately converge on similar evolutionary trajectories and structural aberrations. Evidence of subclonal structure within retinoblastoma cautions the use of targeted chemotherapy for treatment.","abstract":"Retinoblastoma is the most common eye tumour in children, and despite being highly curable, the primary treatment courses (enucleation or chemotherapy) severely impact patient well being and must be carefully chosen. Although retinoblastoma was one of the first tumours to provide clear insight into the genetic basis of cancer, its genomic underpinnings have not yet been fully resolved. The loss of tumour-suppressor gene RB is a main driving event in both hereditary and sporadic retinoblastoma, but this event alone cannot initiate a malignant tumour. A rare subset of retinoblastomas carry wildtype RB, and instead harbour amplification of the MYCN oncogene. However, not all RB1++ tumours carry a MYCN amplification, suggesting other mutations may contribute to pathogenicity. Here, we compare the mutational landscape and evolution of RB1++, RB1+-, and RB1-- retinoblastomas to explore how the presence or absence of a key driver event shapes somatic evolution of the genome. We find CNAs are largely consistent between RB1 genotype groups, but show clear evidence of heterogeneity among RB1-- patients, and uncover novel potential drivers within common chromosomal aberrations including NBAS, CENPF,DFFB, and CHDL1. In contrast, we observe differences in the frequency of coding poiunt mutations among RB1 genoytpe groups for genes including MUC4, EN1, YWAB, and PHF20l1 and further show mutational signatures differ between these groups. We also observe extensive structural rearrangements in both RB1+- and RB1++ samples, as well as evidence of chromothripsis in all samples, often enveloping RB or MYCN, highlighting the general importance of structural variants in retinoblastoma. Finally, we show subclonality is common among retinoblastoma samples, and find copy number aberrations, including RB1 loss and MYCN amplification, occur later in tumour evolution than point mutations. These findings suggest tumours with different RB1 genotypes can experience different mutational processes early in their evolution that manifest mainly through point mutations, but ultimately converge on similar evolutionary trajectories and structural aberrations. Evidence of subclonal structure within retinoblastoma cautions the use of targeted chemotherapy for treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002374","title":"The molecular landscape of colorectal cancer （5 cases）","description":"We performed whole-exome sequencing of tumor samples and adjacent normal mucosae from 5 patients to characterize the genetic alterations in china.","abstract":"We performed whole-exome sequencing of tumor samples and adjacent normal mucosae from 5 patients to characterize the genetic alterations in china.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-14T06:55:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002375","title":"i5_tag_assay","description":"QA assay of barcodes","abstract":"QA assay of barcodes","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002376","title":"Molecular Subtype-specific Biomarkers Improves Colorectal Cancer Prognostication","description":"Colorectal cancer (CRC) is characterized by major inter-tumor diversity that complicates the prediction of disease and treatment outcomes. Recent efforts help resolve this by sub-classification of CRC according to natural molecular subtypes, however, this strategy is not yet able to provide clinicians with improved tools for decision-making. We here present an extended framework for CRC stratification that specifically aims to improve patient prognostication. Using transcriptional profiles from 1,100 CRCs, including a novel set of &gt;300 samples, we identify novel cancer cell and tumor archetypes and suggest the tumor microenvironment as a major prognostic determinant that can be influenced by the microbiome. Notably, our subtyping strategy allowed identification of novel archetype-specific prognostic biomarkers that provided information beyond and independent of UICC-TNM staging, MSI-status and consensus molecular subtyping. The results illustrate that our extended subtyping framework, combining subtyping and subtype-specific biomarkers, could contribute to improved patient prognostication and may form a strong basis for future studies.","abstract":"Colorectal cancer (CRC) is characterized by major inter-tumor diversity that complicates the prediction of disease and treatment outcomes. Recent efforts help resolve this by sub-classification of CRC according to natural molecular subtypes, however, this strategy is not yet able to provide clinicians with improved tools for decision-making. We here present an extended framework for CRC stratification that specifically aims to improve patient prognostication. Using transcriptional profiles from 1,100 CRCs, including a novel set of &gt;300 samples, we identify novel cancer cell and tumor archetypes and suggest the tumor microenvironment as a major prognostic determinant that can be influenced by the microbiome. Notably, our subtyping strategy allowed identification of novel archetype-specific prognostic biomarkers that provided information beyond and independent of UICC-TNM staging, MSI-status and consensus molecular subtyping. The results illustrate that our extended subtyping framework, combining subtyping and subtype-specific biomarkers, could contribute to improved patient prognostication and may form a strong basis for future studies.","study_type":"Other","pubmed_ids":[28494874],"external_links":null,"is_released":true,"released_date":"2017-03-15T07:54:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002377","title":"Tumor-derived exosomes modulate PD-L1 expression in monocytes","description":"In chronic lymphocytic leukemia (CLL), monocytes and macrophages are skewed toward protumorigenic phenotypes, including the release of tumor-supportive cytokines and the expression of immunosuppressive molecules such as programmed cell death 1 ligand 1 (PD-L1). To understand the mechanism driving protumorigenic skewing in CLL, we evaluated the role of tumor cell–derived exosomes in the cross-talk with monocytes. We carried out RNA sequencing and proteome analyses of CLL-derived exosomes and identified noncoding Y RNA hY4 as a highly abundant RNA species that is enriched in exosomes from plasma of CLL patients compared with healthy donor samples. Transfer of CLL-derived exosomes or hY4 alone to monocytes resulted in key CLL-associated phenotypes, including the release of cytokines, such as C-C motif chemokine ligand 2 (CCL2), CCL4, and interleukin-6, and the expression of PD-L1. These responses were abolished in Toll-like receptor 7 (TLR7)–deficient monocytes, suggesting exosomal hY4 as a driver of TLR7 signaling. Pharmacologic inhibition of endosomal TLR signaling resulted in a substantially reduced activation of monocytes in vitro and attenuated CLL development in vivo. Our results indicate that exosome-mediated transfer of noncoding RNAs to monocytes contributes to cancer-related inflammation and concurrent immune escape via PD-L1 expression.","abstract":"In chronic lymphocytic leukemia (CLL), monocytes and macrophages are skewed toward protumorigenic phenotypes, including the release of tumor-supportive cytokines and the expression of immunosuppressive molecules such as programmed cell death 1 ligand 1 (PD-L1). To understand the mechanism driving protumorigenic skewing in CLL, we evaluated the role of tumor cell–derived exosomes in the cross-talk with monocytes. We carried out RNA sequencing and proteome analyses of CLL-derived exosomes and identified noncoding Y RNA hY4 as a highly abundant RNA species that is enriched in exosomes from plasma of CLL patients compared with healthy donor samples. Transfer of CLL-derived exosomes or hY4 alone to monocytes resulted in key CLL-associated phenotypes, including the release of cytokines, such as C-C motif chemokine ligand 2 (CCL2), CCL4, and interleukin-6, and the expression of PD-L1. These responses were abolished in Toll-like receptor 7 (TLR7)–deficient monocytes, suggesting exosomal hY4 as a driver of TLR7 signaling. Pharmacologic inhibition of endosomal TLR signaling resulted in a substantially reduced activation of monocytes in vitro and attenuated CLL development in vivo. Our results indicate that exosome-mediated transfer of noncoding RNAs to monocytes contributes to cancer-related inflammation and concurrent immune escape via PD-L1 expression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-15T12:45:18+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002378","title":"ega-box-216 study","description":"ega-box-216 study","abstract":"ega-box-216 study","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002379","title":"Somatic_mutations_in_twin_breast_cancers","description":"The aim of this study is to investigate the somatic mutations in twins with BRCA1/2 negative breast cancer with no strong family history.","abstract":"The aim of this study is to investigate the somatic mutations in twins with BRCA1/2 negative breast cancer with no strong family history.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-15T14:14:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002380","title":"Botswana 15 autosomal unlinked microsatellites","description":"Population structure was investigated in 990 Botswana individuals according to ethno-linguistics, Bantu and Khoisan, and geography (the nine administrative districts) using the AmpFLSTR Identifiler autosomal microsatellite markers. Genetic diversity and forensic parameters were calculated for the overall population, and according to ethno-linguistics and geography. The overall combined power of exclusion (CPE) was 0.9999965412 and the combined match probability 6,28 x 10-19. CPE was highest for the Khoisan Tuu ethnolinguistic group and the Northeast District at 0.9999582029 and 0.9999922652 respectively. CMP ranged from 6.28 x 10-19 (Khoisan Tuu) to 1,02 x 10-18 (Northwest district). Using pairwise genetic distances (FST), analysis of molecular variance (AMOVA), factorial correspondence analysis (FCA), and the unsupervised Bayesian clustering method found in  STRUCTURE and landscape genetics software TESS, ethno-linguistics were found to have a greater influence on population structure than geography. FCA showed clustering between Bantu and Khoisan, and within the Bantu. This Bantu sub-structuring was not seen with STRUCTURE and TESS, which detected clustering only between Bantu and Khoisan. The patterns of population structure revealed highlight the need for regional reference databases that include ethno-linguistic and geographic location information. These markers have important potential for bio-anthropological studies as well as for forensic applications.","abstract":"Population structure was investigated in 990 Botswana individuals according to ethno-linguistics, Bantu and Khoisan, and geography (the nine administrative districts) using the AmpFLSTR Identifiler autosomal microsatellite markers. Genetic diversity and forensic parameters were calculated for the overall population, and according to ethno-linguistics and geography. The overall combined power of exclusion (CPE) was 0.9999965412 and the combined match probability 6,28 x 10-19. CPE was highest for the Khoisan Tuu ethnolinguistic group and the Northeast District at 0.9999582029 and 0.9999922652 respectively. CMP ranged from 6.28 x 10-19 (Khoisan Tuu) to 1,02 x 10-18 (Northwest district). Using pairwise genetic distances (FST), analysis of molecular variance (AMOVA), factorial correspondence analysis (FCA), and the unsupervised Bayesian clustering method found in  STRUCTURE and landscape genetics software TESS, ethno-linguistics were found to have a greater influence on population structure than geography. FCA showed clustering between Bantu and Khoisan, and within the Bantu. This Bantu sub-structuring was not seen with STRUCTURE and TESS, which detected clustering only between Bantu and Khoisan. The patterns of population structure revealed highlight the need for regional reference databases that include ethno-linguistic and geographic location information. These markers have important potential for bio-anthropological studies as well as for forensic applications.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-16T05:17:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002381","title":"Human_PSCs_derived_BAT_RNAseq_analysis","description":"Obesity and associated metabolic complications are major health problems. Here we propose a strategy focused on targeting the mechanisms controlling energy dissipation to create negative energy balance. The brown adipose tissue (BAT) is specialised in energy dissipation in response to environmental stimuli such as cold and increased lipid rich hypercaloric intake, a process referred as adaptive thermogenesis. This energy dissipating role of BAT is mediated by uncoupling protein 1 (UCP1). The relevance of BAT activation to energy balance is well established in murine models. The realisation that functional BAT is also found in adult humans is much more recent. An inverse relationship between adiposity, diabetes and BAT activity has been observed. These results support the concept that increasing a) BAT mass, b) activity o c) recruitment of beige cells could be a safe and efficient strategy to prevent or treat obesity and its associated complications. Current cellular and developmental models of adipogenesis have limited therapeutic potential and constrains the discovery of cell fate mechanisms involved in human BAT development. To surmount these issues, human pluripotent stem cells (PSCs) in vitro differentiation represents a promising complementary model of brown adipogenesis.\nWithin the pump-priming project “ES/IPS cells differentiation to brown/beige adipocytes as an anti-obesity strategy”, we developed a model of human PSC-derived brown adipose tissue progenitors (mesodermal, early, late progenitors) and of mature brown adipocyte.     \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"To determine, by RNAseq, the transcriptome of specific precursors corresponding to different time points of BAT development and differentiation, mature brown adipocytes as well as activated mature brown adipocyte to gain new insight into human BAT development/ differentiation and activation. We will use the undifferentiated state as an internal control of the experiment. Trascriptome analysis will be performed at the Sanger Institute.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002382","title":"Field_effect_of_healthy_and_diseased_livers","description":"Recent work in the Campbell group has revealed somatic mutations present in normal, non-cancerous human skin. A subset of the mutations conferred selective advantages to the host cells, leading to clonal expansions and raising the risk for future cancer development. Capturing such somatic mutations in normal tissue is important to advance our understanding about carcinogenesis and could provide prospective medical insights. \nIn this project, our goal is to detect somatic mutations in normal (pre-cancerous) liver tissue. Using Laser Microdissection technology, we will dissect individual liver lobules from patient samples and submit these to sequencing. For each patient sample, we aim to sequence multiple lobules to characterise the mutagenic burden. Samples will be taken from patients with different liver disease aetiologies, including alcoholism and obesity, with a view on distinguishing the prevalent mutation types occurring in each disease context.\nWe will perform targeted sequencing, initially using the WTSI cancer panel. Later we aim to use a novel bait set that captures both cancer genes as well as genes relevant to the non-cancerous samples (ie. genes implicated in hereditary disorders, immune sequences).","abstract":"In this study we will submit samples microdissected from liver sections using laser microscopy. We aim to capture somatic mutations occuring in liver hepatocytes in patients not afflicted with liver disease and in patients afflicted with different liver disease aetiologies, including alcoholism, obesity and hepatocellular carcinoma. For each patient, we aim to submit multiple (20 to 100) microdissections, each of which encompasses ca. 500 cells. In addition, for each patient we will submit one sample for bulk sequencing.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-16T13:45:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002383","title":"Long_range_haploid_sequencing_in_90_samples_of_human_DNA_","description":"This project is part of a wider project of obtaining haploid sequences of DNA from Pygmy individuals from South East Asia and Pacific put together by Andrea Migliano (UCL, London), Eske Wilerslev (Cambridge) Jaume Bertranpetit (UPF), and Richard Durbin (Sanger Institute)\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Long range haploid sequencing in 90 samples of human DNA","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002384","title":"Heartbeat test study for test dataset","description":"Heartbeat test study for test dataset","abstract":"Heartbeat test study for test dataset","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002385","title":"Whole-genome sequencing of sub-Saharan African populations","description":"This project comprises whole-genome sequencing of family trios and individuals from several ethnic groups living in sub-Saharan African populations.  These data were collected as part of the MalariaGEN Consortial Project 3 (https://www.malariagen.net/projects/consortial-project-3).","abstract":"This project comprises whole-genome sequencing of family trios and individuals from several ethnic groups living in sub-Saharan African populations.  These data were collected as part of the MalariaGEN Consortial Project 3 (https://www.malariagen.net/projects/consortial-project-3).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002386","title":"Isolation_and_characterisation_of_human_cone_photoreceptors_towards_a_cell_replacement_therapy_for_retinal_dystrophies","description":"1. The study is to compare the single cell transcriptome of AAV-labelled cone cells from 3D human iPSC-derived optic cups vs AAV-labelled cone cells from human foetal retina. Cells from these samples have been FAC sorted into a 384 well plate (189 cells per sample; controls form the remaining 6 wells). Tasks to be performed at the WTSI include cDNA synthesis, quality control and single cell RNA sequencing.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"nherited retinal dystrophies resulting in the death of the light-sensitive rod and cone photoreceptor cells are a major cause of incurable blindness. Cone loss has the greatest impact on vision as although less abundant than rods, cones are indispensable for colour vision and high visual acuity. Human pluripotent stem cell differentiation cultures provide a powerful platform to model retinal diseases and a potential renewable source of cone photoreceptors for cell replacement therapy. However, little is currently known about the developmental expression profile of human cone photoreceptors. This project aimed to isolate cone photoreceptors from the human foetal retina with those from human induced pluripotent stem cell (hiPSC)-derived retinal cultures to compare their transcriptome, in addition to identifying novel cell surface markers of cones to develop a cell isolation strategy.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002387","title":"Pancreatic_Differentiation_Single_Cell_RNA_sequencing","description":"The current protocol of pancreatic differentiation used in the Vallier lab to generate pancreatic beta-like cells from human pluripotent stem cells (hPSCs) has been adapted from a seven stage protocol developed previously in the lab and generates beta-like cells which produce insulin accordingly in response to low or high levels glucose. These stages are definitive endoderm, foregut, early pancreatic progenitors, pancreatic progenitors, endocrine progenitors, early endocrine cells, and beta-like cells. After the pancreatic progenitor stage, the cell populations become too heterogenous to study gene expression in the cell type of interest using bulk RNA analysis. In addition, the different cell types that contribute to the heterogenity of the population are not well characterised. To address these issues, we would like to carry out single cell analysis at each major stage of the pancreatic differentiation protocol to; \n1.) investigate gene expression in our cell type of interest - especially at later stages of the protocol; 2.) characterise the other cell types present in the populations. \n\nWe plan on performing these analyses for at least 2 wild-type cell lines, a HNF1B knockout line, and beta-like cells that have been treated with compounds known to affect glucose secretion. These data will provide valuable insight into the signaling pathways that control pancreatic differentiation and will allow us to study cell types that could not previously isolated in large enough quantities to carry out gene expression analysis.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The current protocol of pancreatic differentiation used in the Vallier lab to generate pancreatic beta-like cells from human pluripotent stem cells (hPSCs) has been adapted from a seven stage protocol developed previously in the lab (Cho C et al., 2012) and generates beta-like cells which produce insulin accordingly in response to low or high levels glucose. These stages are definitive endoderm, foregut, early pancreatic progenitors, pancreatic progenitors, endocrine progenitors, early endocrine cells, and beta-like cells. After the pancreatic progenitor stage, the cell populations become too heterogenous to study gene expression in the cell type of interest using bulk RNA analysis. In addition, the different cell types that contribute to the heterogenity of the population are not well characterised. To address these issues, we would like to carry out single cell analysis at each major stage of the pancreatic differentiation protocol to; 1.) investigate gene expression in our cell type of interest - especially at later stages of the protocol; 2.) characterise the other cell types present in the populations. \nWe plan on performing these analyses for at least 2 wild-type cell lines, a HNF1B knockout line, and beta-like cells that have been treated with compounds known to affect glucose secretion. These data will provide valuable insight into the signaling pathways that control pancreatic differentiation and will allow us to study cell types that could not previously isolated in large enough quantities to carry out gene expression analysis.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002388","title":"2017_AML_WGS","description":"This 2017_AML_WGS study includes 10 paired samples derived from Korean AML paitients.\n10 AML Bone Marrow samples were collected and paired with each normal(Saliva or BM derived) sequencing data.\nThe results of this WGS study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.","abstract":"This 2017_AML_WGS study includes 10 paired samples derived from Korean AML paitients.\n10 AML Bone Marrow samples were collected and paired with each normal(Saliva or BM derived) sequencing data.\nThe results of this WGS study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-21T00:35:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002389","title":"Single_Cell_Gene_Expression_in_Regulatory_T_cells_in_human","description":"In this study, we intend to look further into the complexity of Regulatory T cell population, which has recently started to be unveiled. The single-cell transcriptomics approach we are undertaking will help us finding relevant differences between subpopulations of Tregs within and across several lymphoid and non-lymphoid tissues. We thus expect to get a good picture of how Tregs are structurally organized, how they adapt and how they are stabilized in different contexts. \n     \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"During the last decades, Tregs have arisen as key orchestrators of immune tolerance. Representing 1-10% of CD4+ T cells, these CD4+Foxp3+ cells are known to be present and to act on different lymphoid and non-lymphoid tissues, sustaining tolerance through yet incompletely described mechanisms. \nWe aim at identifying  and characterizing the different subpopulations of Tregs, shedding a light on subpopulation-specific roles, mechanisms of action and features.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002390","title":"Genomic consequences of aberrant DNA repair mechanisms stratify ovarian cancer histotypes","description":"Aberrant DNA repair processes are a hallmark of human tumours. How these deficiencies variously impact the genomes of ovarian cancer between and within histotypes remains unknown. We studied the whole genome pointmutation and structural variation patterns of 133 tumours (59 high grade serous (HGSC), 35 clear cell (CCOC), 29 endometrioid (ENOC), and 10 adult granulosa cell tumours (GCT)) as a substrate for class discovery in ovarian cancer. Ab-initio clustering of integrated point mutation and structural variation signatures revealed seven novel subgroups, comprising between and within histotype stratification. Prevalence of fold-back inversions (FBI) co-localised with high level amplification events divided HGSC into two prognostically significant subgroups. This finding was recapitulated in two additional independent cohorts (total n=576 cases), and transcended gene based mutation status and gene expression as prognostically relevant features of HGSC. CCOC were divided into one group harbouring a signature reflective of active genome editing via APOBEC enzymes (26%) and a complementary group with an age-relatedmutational signature. ENOC were divided intomicrosatellite instable (MSI) cases (28%) with a distinctmismatch repairmutation signature and an outlying mutation rate, with the remainder of cases distributed amongst the remaining six groups. We suggest the FBI, MSI, and APOBEC groups represent biologic strata that could direct treatment strategies. Taken together, our work establishes the efficacy of the somatic genome as a biomarker to stratify ovarian cancers, simultaneously identifying patients that may benefit from emerging therapeutics and distinct subgroups within classic ovarian cancer histotypes.","abstract":"Aberrant DNA repair processes are a hallmark of human tumours. How these deficiencies variously impact the genomes of ovarian cancer between and within histotypes remains unknown. We studied the whole genome pointmutation and structural variation patterns of 133 tumours (59 high grade serous (HGSC), 35 clear cell (CCOC), 29 endometrioid (ENOC), and 10 adult granulosa cell tumours (GCT)) as a substrate for class discovery in ovarian cancer. Ab-initio clustering of integrated point mutation and structural variation signatures revealed seven novel subgroups, comprising between and within histotype stratification. Prevalence of fold-back inversions (FBI) co-localised with high level amplification events divided HGSC into two prognostically significant subgroups. This finding was recapitulated in two additional independent cohorts (total n=576 cases), and transcended gene based mutation status and gene expression as prognostically relevant features of HGSC. CCOC were divided into one group harbouring a signature reflective of active genome editing via APOBEC enzymes (26%) and a complementary group with an age-relatedmutational signature. ENOC were divided intomicrosatellite instable (MSI) cases (28%) with a distinctmismatch repairmutation signature and an outlying mutation rate, with the remainder of cases distributed amongst the remaining six groups. We suggest the FBI, MSI, and APOBEC groups represent biologic strata that could direct treatment strategies. Taken together, our work establishes the efficacy of the somatic genome as a biomarker to stratify ovarian cancers, simultaneously identifying patients that may benefit from emerging therapeutics and distinct subgroups within classic ovarian cancer histotypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-21T18:19:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002391","title":"obsolete--Failed attempt to submit HNSCC (NYGC Illumina), Do not proceed","description":"TODO: STUDY ABSTRACT AS IT COULD APPEAR IN A\n                PUBLICATION","abstract":"TODO: STUDY ABSTRACT AS IT COULD APPEAR IN A\n                PUBLICATION","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002392","title":"obsolete--Empty Study - Accidentally created","description":"To be filled later","abstract":"To be filled later","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002393","title":"Genomic landscape of oral cancers (Complete Genomics WGS)","description":"Human papillomavirus (HPV) is a necessary but insufficient cause of a subset of oral squamous cell carcinomas (OSCC) that is increasing markedly in frequency. To identify contributory, secondary genetic alterations in these cancers, we used comprehensive genomics methods to compare 149 HPV-positive and 335 HPV-negative OSCC tumor/normal pairs. Different behavioral risk factors underlying the two OSCC types were reflected in distinctive genomic mutational signatures. In HPV-positive OSCC, the signatures of APOBEC cytosine deaminase editing, associated with anti-viral immunity, were strongly linked to overall mutational burden. By contrast, in HPV-negative OSCC, T&gt;C substitutions in the sequence context 5’-ATN-3’ correlated with tobacco exposure. Universal expression of HPV E6*1 and E7 oncogenes was a sine qua non of HPV-positive OSCC. Significant enrichment of somatic mutations was confirmed or newly identified in PIK3CA, KMT2D, FGFR3, FBXW7, DDX3X, PTEN, TRAF3, RB1, CYLD, RIPK4, ZNF750, EP300, CASZ1, TAF5, RBL1, IFNGR1 and NFKBIA. Of these, many affect host pathways already targeted by HPV oncoproteins, including the p53 and pRB pathways, or disrupt host defenses against viral infections, including interferon and nuclear factor-B signaling. Frequent copy number changes were associated with concordant changes in gene expression. Chr. 11q (including CCND1) and 14q (including DICER1 and AKT1) were recurrently lost in HPV-positive OSCC, in contrast to their gains in HPV-negative OSCC. High-ranking variant allele fractions implicated ZNF750, PIK3CA and EP300 mutations as candidate driver events in HPV-positive cancers. We conclude that virus-host interactions cooperatively shape the unique genetic features of these cancers, distinguishing them from their HPV-negative counterparts.","abstract":"Human papillomavirus (HPV) is a necessary but insufficient cause of a subset of oral squamous cell carcinomas (OSCC) that is increasing markedly in frequency. To identify contributory, secondary genetic alterations in these cancers, we used comprehensive genomics methods to compare 149 HPV-positive and 335 HPV-negative OSCC tumor/normal pairs. Different behavioral risk factors underlying the two OSCC types were reflected in distinctive genomic mutational signatures. In HPV-positive OSCC, the signatures of APOBEC cytosine deaminase editing, associated with anti-viral immunity, were strongly linked to overall mutational burden. By contrast, in HPV-negative OSCC, T&gt;C substitutions in the sequence context 5’-ATN-3’ correlated with tobacco exposure. Universal expression of HPV E6*1 and E7 oncogenes was a sine qua non of HPV-positive OSCC. Significant enrichment of somatic mutations was confirmed or newly identified in PIK3CA, KMT2D, FGFR3, FBXW7, DDX3X, PTEN, TRAF3, RB1, CYLD, RIPK4, ZNF750, EP300, CASZ1, TAF5, RBL1, IFNGR1 and NFKBIA. Of these, many affect host pathways already targeted by HPV oncoproteins, including the p53 and pRB pathways, or disrupt host defenses against viral infections, including interferon and nuclear factor-B signaling. Frequent copy number changes were associated with concordant changes in gene expression. Chr. 11q (including CCND1) and 14q (including DICER1 and AKT1) were recurrently lost in HPV-positive OSCC, in contrast to their gains in HPV-negative OSCC. High-ranking variant allele fractions implicated ZNF750, PIK3CA and EP300 mutations as candidate driver events in HPV-positive cancers. We conclude that virus-host interactions cooperatively shape the unique genetic features of these cancers, distinguishing them from their HPV-negative counterparts.","study_type":"Other","pubmed_ids":[30563911],"external_links":null,"is_released":true,"released_date":"2017-03-22T00:39:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002394","title":"CRISPR_targeted_sequence_analysis___Amplicon_MiSeq","description":"For an in-depth analysis into CRISPR-induced mutation, CRISPR-targeted regions will be amplified and sequenced using MiSeq.","abstract":"For an in-depth analysis into CRISPR-induced mutation, CRISPR-targeted regions will be amplified and sequenced using MiSeq.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002395","title":"Human_cell_line_authentication__WES","description":"Human cell lines will be periodically sequenced. Comparsion of gene sequences over time will allow the detection of changes in cell line populations.","abstract":"Human cell lines will be periodically sequenced. Comparsion of gene sequences over time will allow the detection of changes in cell line populations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002396","title":"Microcystic_adnexal_carcinoma_tumour_WES___Redman","description":"Microcystic adnexal carcinoma (MAC) is a rare, malignant tumour often defined as a low-grade sweat gland carcinoma. These tumours usually occur on the head and neck, particularly the face. Microcystic adnexal carcinomas have little metastatic potential but may show aggressive local invasion. Here we sequence a tumour germline pair.","abstract":"Microcystic adnexal carcinoma (MAC) is a rare, malignant tumour often defined as a low-grade sweat gland carcinoma. These tumours usually occur on the head and neck, particularly the face. Microcystic adnexal carcinomas have little metastatic potential but may show aggressive local invasion. Here we sequence a tumour germline pair.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002397","title":"TO DELETE","description":"TO DELETE","abstract":"TO DELETE","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002398","title":"WGS of T-cell and NK-cell lymphoma for ICGC (NKTL-SG)","description":"Lymphomas are malignancies originating from the lymphatic system and there is a worldwide significant increase in incidences of this cancer. Lymphomas can be further classified into 2 categories namely Hodgkin’s (HL), and Non-Hodgkin’s lymphoma (NHL). The latter can be divided further into B, T and NK cell NHL. Peripheral T-cell lymphoma (PTCL) and Natural Killer/ T-cell lymphoma (NKTL) arise from mature T lymphocytes and NK cells. The more common subtypes include NKTL, PTCL not-otherwise-specified (PTCL-NOS), systemic anaplastic large cell lymphoma (ALCL), follicular PTCL (F-PTCL), angioimmunoblastic T-cell lymphoma (AITL) and enteropathy-associated T-cell lymphoma (EATL). \n\nWhole genome analyses on T-cell and NK-cell lymphoma samples from various countries to gain a better understanding of the pathogenesis and biology of these tumors. The comprehensive profiling and comparison among patients from various countries with different etiopathogenesis will hopefully facilitate the elucidation of key pathways and underlying molecular mechanisms driving these cancers, opening up novel therapeutic strategies in the future.","abstract":"Lymphomas are malignancies originating from the lymphatic system and there is a worldwide significant increase in incidences of this cancer. Lymphomas can be further classified into 2 categories namely Hodgkin’s (HL), and Non-Hodgkin’s lymphoma (NHL). The latter can be divided further into B, T and NK cell NHL. Peripheral T-cell lymphoma (PTCL) and Natural Killer/ T-cell lymphoma (NKTL) arise from mature T lymphocytes and NK cells. The more common subtypes include NKTL, PTCL not-otherwise-specified (PTCL-NOS), systemic anaplastic large cell lymphoma (ALCL), follicular PTCL (F-PTCL), angioimmunoblastic T-cell lymphoma (AITL) and enteropathy-associated T-cell lymphoma (EATL). \n\nWhole genome analyses on T-cell and NK-cell lymphoma samples from various countries to gain a better understanding of the pathogenesis and biology of these tumors. The comprehensive profiling and comparison among patients from various countries with different etiopathogenesis will hopefully facilitate the elucidation of key pathways and underlying molecular mechanisms driving these cancers, opening up novel therapeutic strategies in the future.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-27T04:12:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002399","title":"UK Biobank whole cohort directly genotyped and imputed data (~500,000 participants)","description":"Genotype data is available for all 500,000 participants in the UK Biobank cohort. Genotyping has been performed using the Affymetrix UK BiLEVE Axiom array on an initial 50,000 participants and the remaining 450,000 participants have been genotyped using the Affymetrix UK Biobank Axiom® array. The two arrays are extremely similar (with over 95% common content).Quality control and imputation (to over 90 million SNPs, indels and large structural variants) has been  performed by a collaborative group headed by the Wellcome Trust Centre for Human Genetics.The following data are available:* A clean set of QC’ed genotype calls* Confidence values that a genotype call is correct* Intensity data to generate cluster plots* Extensive QC information regarding SNPs and samples including SNP metrics, batch effects, population structure and relatedness* Imputed dataFor further information, please refer to the UK Biobank website","abstract":"Genotype data is available for all 500,000 participants in the UK Biobank cohort. Genotyping has been performed using the Affymetrix UK BiLEVE Axiom array on an initial 50,000 participants and the remaining 450,000 participants have been genotyped using the Affymetrix UK Biobank Axiom® array. The two arrays are extremely similar (with over 95% common content).Quality control and imputation (to over 90 million SNPs, indels and large structural variants) has been  performed by a collaborative group headed by the Wellcome Trust Centre for Human Genetics.The following data are available:* A clean set of QC’ed genotype calls* Confidence values that a genotype call is correct* Intensity data to generate cluster plots* Extensive QC information regarding SNPs and samples including SNP metrics, batch effects, population structure and relatedness* Imputed dataFor further information, please refer to the UK Biobank website","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001002400","title":"Biological insights from the whole genome sequences of human embryonic stem cell lines","description":"Human embryonic stem cells (hESCs) are a powerful tool for the study of human development and can form the basis of cellular disease models or therapies. However, the genetic make-up and stability of hESCs has not been systematically studied at a genome-wide level with single nucleotide resolution. We therefore sequenced the whole genome and whole exomes of widely available hESC. This online resource will enable investigators to access raw sequencing data in order to interrogate cell lines for different disease- and trait-associated genetic variants.","abstract":"Human embryonic stem cells (hESCs) are a powerful tool for the study of human development and can form the basis of cellular disease models or therapies. However, the genetic make-up and stability of hESCs has not been systematically studied at a genome-wide level with single nucleotide resolution. We therefore sequenced the whole genome and whole exomes of widely available hESC. This online resource will enable investigators to access raw sequencing data in order to interrogate cell lines for different disease- and trait-associated genetic variants.","study_type":"Other","pubmed_ids":[28445466],"external_links":null,"is_released":true,"released_date":"2017-03-27T17:01:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002401","title":"Cell of origin-specific genetic alterations and chromosomal instability have therapeutic and immunologic impact in diffuse large B-cell lymphoma","description":"Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype worldwide, is a diverse disease with distinct molecular and clinical features in which ~40% of patients experience treatment failure. To understand the molecular distinctions and their therapeutic relevance specific to Cell-of-Origin (COO) in DLBCL, for the first time we performed an integrative genomic and transcriptomic analysis of biopsies from a large population registry-based cohort of uniformly treated patients with de novo DLBCL. We identified that NFATC1 amplification was significantly enriched in ABC-DLBCL with prognostic significance. Distinct impact of copy number alterations on PI3K-AKT signaling pathway gene expression was observed in GCB-DLBCL relative to ABC-DLBCL. Furthermore, deletions of INPP4B and PTEN (implicating disrupted PI3K-AKT signaling), as well as activated phosphorylation of AKT were indicators of poor prognosis in GCB-DLBCL, suggesting a potential therapeutic target in this subtype. Finally, genome-wide analysis revealed chromosomal instability stratifies clinically and genetically distinct subgroups in DLBCL, which were associated with distinct tumor immune microenvironments across COO subtypes.","abstract":"Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype worldwide, is a diverse disease with distinct molecular and clinical features in which ~40% of patients experience treatment failure. To understand the molecular distinctions and their therapeutic relevance specific to Cell-of-Origin (COO) in DLBCL, for the first time we performed an integrative genomic and transcriptomic analysis of biopsies from a large population registry-based cohort of uniformly treated patients with de novo DLBCL. We identified that NFATC1 amplification was significantly enriched in ABC-DLBCL with prognostic significance. Distinct impact of copy number alterations on PI3K-AKT signaling pathway gene expression was observed in GCB-DLBCL relative to ABC-DLBCL. Furthermore, deletions of INPP4B and PTEN (implicating disrupted PI3K-AKT signaling), as well as activated phosphorylation of AKT were indicators of poor prognosis in GCB-DLBCL, suggesting a potential therapeutic target in this subtype. Finally, genome-wide analysis revealed chromosomal instability stratifies clinically and genetically distinct subgroups in DLBCL, which were associated with distinct tumor immune microenvironments across COO subtypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002402","title":"Comprehensive investigation of genome architecture of papillary thyroid cancer with whole-exon sequencing in the Chinese population.","description":"In this study, we performed whole-exon sequencing (WES) of 50 paired PTC tumors and adjacent normal tissues to identify novel potential biomarkers. We extracted mutational signatures which induce somatic mutations. Moreover, we observed copy number changes frequently occurring in some cancer related genes. Our study covers a comprehensive genetic framework that can be used in clinical trials and treatment modalities in PTC.","abstract":"In this study, we performed whole-exon sequencing (WES) of 50 paired PTC tumors and adjacent normal tissues to identify novel potential biomarkers. We extracted mutational signatures which induce somatic mutations. Moreover, we observed copy number changes frequently occurring in some cancer related genes. Our study covers a comprehensive genetic framework that can be used in clinical trials and treatment modalities in PTC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-28T08:02:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002403","title":"HNSCC HPV Integration Analysis (HPV-CGI)","description":"TODO: STUDY ABSTRACT AS IT COULD APPEAR IN A\n                PUBLICATION","abstract":"TODO: STUDY ABSTRACT AS IT COULD APPEAR IN A\n                PUBLICATION","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002404","title":"Comprehensive investigation of genome architecture of gastric adenocarcinoma with whole-genome sequencing in the Chinese population.","description":"In this study, we performed whole-genome sequencing (WGS) of 214 paired GC tumors and adjacent normal tissues to identify novel potential biomarkers. We extracted mutational signatures which induce somatic mutations and classified GC tumors into four groups with significantly different prognosis. Moreover, we observed copy number changes and structural variations frequently occurring in some cancer related genes. Our study covers a comprehensive genetic framework that can be used in clinical trials and treatment modalities in GC.","abstract":"In this study, we performed whole-genome sequencing (WGS) of 214 paired GC tumors and adjacent normal tissues to identify novel potential biomarkers. We extracted mutational signatures which induce somatic mutations and classified GC tumors into four groups with significantly different prognosis. Moreover, we observed copy number changes and structural variations frequently occurring in some cancer related genes. Our study covers a comprehensive genetic framework that can be used in clinical trials and treatment modalities in GC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-29T02:58:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002405","title":"Targeted resequencing of ribosomal proteins in multiple myeloma patient samples.","description":"We studied 38 multiple myeloma samples to discover mutations in ribosomal proteins. To this end, we ran a specifically designed targeted resequencing study to resequence the coding regions of all ribosomal proteins.","abstract":"We studied 38 multiple myeloma samples to discover mutations in ribosomal proteins. To this end, we ran a specifically designed targeted resequencing study to resequence the coding regions of all ribosomal proteins.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-29T13:12:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002406","title":"Bisulfite-converted duplexes for the strand-specific detection and quantification of rare mutations","description":"The identification of mutations that are present at low frequencies in clinical samples is an essential component of precision medicine. The development of molecular barcoding for next generation sequencing has greatly enhanced the sensitivity of detecting such mutations by massively parallel sequencing. However, further improvements in specificity would be useful for a variety of applications. We herein describe a technology (BiSeqS) that can increase the specificity of sequencing by at least two orders of magnitude over and above that achieved with molecular barcoding and can be applied to any massively parallel sequencing instrument. BiSeqS employs bisulfite treatment to distinguish the two strands of molecularly barcoded DNA; its specificity arises from the requirement for the same mutation to be identified in both strands. Because no library preparation is required, the technology permits very efficient use of the template DNA as well as sequence reads, which are nearly all confined to the amplicons of interest. Such efficiency is critical for clinical samples, such as plasma, in which only tiny amounts of DNA are often available. We show here that BiSeqS can be applied to evaluate transversions, as well as small insertions or deletions, and can reliably detect one mutation among &gt;10,000 wild type molecules.","abstract":"The identification of mutations that are present at low frequencies in clinical samples is an essential component of precision medicine. The development of molecular barcoding for next generation sequencing has greatly enhanced the sensitivity of detecting such mutations by massively parallel sequencing. However, further improvements in specificity would be useful for a variety of applications. We herein describe a technology (BiSeqS) that can increase the specificity of sequencing by at least two orders of magnitude over and above that achieved with molecular barcoding and can be applied to any massively parallel sequencing instrument. BiSeqS employs bisulfite treatment to distinguish the two strands of molecularly barcoded DNA; its specificity arises from the requirement for the same mutation to be identified in both strands. Because no library preparation is required, the technology permits very efficient use of the template DNA as well as sequence reads, which are nearly all confined to the amplicons of interest. Such efficiency is critical for clinical samples, such as plasma, in which only tiny amounts of DNA are often available. We show here that BiSeqS can be applied to evaluate transversions, as well as small insertions or deletions, and can reliably detect one mutation among &gt;10,000 wild type molecules.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-29T16:53:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002407","title":"Integration of genome profiling and drug screening has revealed gene-drug association in pan-cancer analysis (Do not release)","description":"Gene-drug association (Do not release)","abstract":"Gene-drug association (Do not release)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002408","title":"Whole Genome Sequencing of Liver Cancers","description":"Genomic alterations driving tumorigenesis result from the interaction of environmental exposures and endogeneous cellular processes. With a diversity of risk factors including viral infection, carcinogenic exposures and metabolic diseases, liver cancer is an ideal model to study these interactions. Whole genome sequencing of liver tumors identified 10 mutational signatures showing distinct relationships with environmental exposures, replication and transcription. Transcription-coupled damage was specifically associated with the liver-specific signature 16 and alcohol intake. Flood of indels were identified in very highly expressed hepato-specific genes, likely resulting from replication-transcription collisions. Reconstruction of sub-clonal architecture revealed mutational signature evolution during tumor development exemplified by the vanishing of aflatoxin-B1 signature in African migrants. These findings shed new light on the natural history of liver cancers","abstract":"Genomic alterations driving tumorigenesis result from the interaction of environmental exposures and endogeneous cellular processes. With a diversity of risk factors including viral infection, carcinogenic exposures and metabolic diseases, liver cancer is an ideal model to study these interactions. Whole genome sequencing of liver tumors identified 10 mutational signatures showing distinct relationships with environmental exposures, replication and transcription. Transcription-coupled damage was specifically associated with the liver-specific signature 16 and alcohol intake. Flood of indels were identified in very highly expressed hepato-specific genes, likely resulting from replication-transcription collisions. Reconstruction of sub-clonal architecture revealed mutational signature evolution during tumor development exemplified by the vanishing of aflatoxin-B1 signature in African migrants. These findings shed new light on the natural history of liver cancers","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-30T16:19:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002409","title":"Human_primary_melanoma_project","description":"Mutational burden and profiles to be studied in approx. 500 human primary melanomas with matched normal samples, part of the Leeds melanoma cohort. New custom design targeted capture panel covering melanoma-specific copy number alterations, promoter mutations, gene fusions, coding genes, HLA regions and IFNg/JAK/STAT pathway genes.","abstract":"Mutational burden and profiles to be studied in approx. 500 human primary melanomas with matched normal samples, part of the Leeds melanoma cohort. New custom design targeted capture panel covering melanoma-specific copy number alterations, promoter mutations, gene fusions, coding genes, HLA regions and IFNg/JAK/STAT pathway genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-03-31T13:06:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002410","title":"Suppressors and activators of JAK-STAT signaling at diagnosis and relapse of acute lymphoblastic leukemia in Down Syndrome","description":"Children with Down Syndrome (DS) are prone to development of high risk B-cell precursor ALL (DS-ALL) that differs genetically from most sporadic pediatric ALLs. Increased expression of CRLF2, the receptor to thymic stromal lymphopoietin (TSLP) characterizes about half of DS-ALLs and also a subgroup of sporadic “Philadelphia-like ALLs”. To understand the pathogenesis of relapsed DS-ALL we performed integrative genomic analysis of 25 matched diagnosis remission and relapse DS-ALLs.  We found that the CRLF2 rearrangements are early events during DS-ALL evolution and generally stable between diagnoses and relapse. Secondary activating signaling events in JAK-STAT/RAS pathway were ubiquitous but highly redundant between diagnosis and relapse, suggesting that signaling is essential but that no specific mutations are “relapse driving”. We further found that activated JAK2 may be naturally suppressed in 25% of CRLF2 positive DS-ALL by loss-of-function aberrations in USP9X, a deubuitinase previously shown to stabilize the activated phosphorylated JAK2. Interrogation of large ALL genomic databases extended our findings up to 25% of CRLF2 positive, “Ph like” ALLs. Pharmacological or genetic inhibition of USP9X as well as treatment with low-dose Ruxolitinib enhanced the survival of pre-B ALL cells overexpressing mutated JAK2. Thus, somehow counterintuitive, we found that suppression of JAK-STAT “hyper-signaling” may be beneficial to leukemic B cell precursors. This and the reduction of JAK mutated clones at relapse suggest that the therapeutic effect of JAK specific inhibitors may be limited. Rather, combined signaling inhibitors or direct targeting of the TSLP receptor may be a useful therapeutic strategy for DS-ALL.","abstract":"Children with Down Syndrome (DS) are prone to development of high risk B-cell precursor ALL (DS-ALL) that differs genetically from most sporadic pediatric ALLs. Increased expression of CRLF2, the receptor to thymic stromal lymphopoietin (TSLP) characterizes about half of DS-ALLs and also a subgroup of sporadic “Philadelphia-like ALLs”. To understand the pathogenesis of relapsed DS-ALL we performed integrative genomic analysis of 25 matched diagnosis remission and relapse DS-ALLs.  We found that the CRLF2 rearrangements are early events during DS-ALL evolution and generally stable between diagnoses and relapse. Secondary activating signaling events in JAK-STAT/RAS pathway were ubiquitous but highly redundant between diagnosis and relapse, suggesting that signaling is essential but that no specific mutations are “relapse driving”. We further found that activated JAK2 may be naturally suppressed in 25% of CRLF2 positive DS-ALL by loss-of-function aberrations in USP9X, a deubuitinase previously shown to stabilize the activated phosphorylated JAK2. Interrogation of large ALL genomic databases extended our findings up to 25% of CRLF2 positive, “Ph like” ALLs. Pharmacological or genetic inhibition of USP9X as well as treatment with low-dose Ruxolitinib enhanced the survival of pre-B ALL cells overexpressing mutated JAK2. Thus, somehow counterintuitive, we found that suppression of JAK-STAT “hyper-signaling” may be beneficial to leukemic B cell precursors. This and the reduction of JAK mutated clones at relapse suggest that the therapeutic effect of JAK specific inhibitors may be limited. Rather, combined signaling inhibitors or direct targeting of the TSLP receptor may be a useful therapeutic strategy for DS-ALL.","study_type":"Other","pubmed_ids":[28461505],"external_links":null,"is_released":true,"released_date":"2017-04-01T09:36:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002411","title":"Orphan_Tumour_Study___Wilms_tumour","description":"Whole genome sequencing study aiming to uncover the developmental histories of Bilateral Wilms Tumour","abstract":"Whole genome sequencing study aiming to uncover the developmental histories of Bilateral Wilms Tumour","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002412","title":"Characterising_cellular_pathways_underlying_CD3_CD28_activation_of_human_CD4__cells","description":"We devised an approach to disentangle the TCR and CD28 pathways upon stimulation in naive and memory primary human CD4+ T cells (Tcons) in response to defined stimulatory signals. Sorted Tcons were activated using a titration of anti-CD3 and anti-CD28 in combination as well as individually. As a control we cultured cells in the same conditions but without the stimuli. In total, we defined seven conditions from four individuals for sequencing.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Two signals are necessary for a successful T cell activation; interaction of the T cell receptor (TCR) with the major histocompatibility complex II (MHC) antigens on the antigen presenting cells (APC) and interaction of the CD28 receptor on the lymphocyte with B7 proteins presented by the APC.  The role of CD28 receptor in T cell activation remains poorly understood, with an ongoing debate on whether it amplifies TCR based signal, drives unique changes in the cell or whether it is neede at all for certain T cell subsets activation. Self-recognition by TCR can lead to autoimmunity, highlighting the importance to better study these pathways using genomics tools.\nWe aimed to decouple the T cell activation signals in order to better understand their role in immune response. I believe that by joining immunophenotyping with gene expression studies we can elucidate the pathways engaged by CD28 co-stimulation for a successful T cell activation in naive and memory cells. That will also allow us to explore the effect of increasing TCR signal in the differentiation of naive cells. Looking at gene expression variability between individuals, as well as their threshold response to a stimulus, we can gain an insight into the role of genetic variants in activation processes of CD4+ cells.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002413","title":"Field_effect_of_healthy_and_diseased_livers_WGS","description":"Recent work in the Campbell group has revealed somatic mutations present in normal, non-cancerous human skin. A subset of the mutations conferred selective advantages to the host cells, leading to clonal expansions and raising the risk for future cancer development. Capturing such somatic mutations in normal tissue is important to advance our understanding about carcinogenesis and could provide prospective medical insights. \n\nIn this project, our goal is to detect somatic mutations in normal (pre-cancerous) liver tissue. Using Laser Microdissection technology, we will dissect individual liver lobules from patient samples and submit these to sequencing. For each patient sample, we aim to sequence multiple lobules to characterise the mutagenic burden. Samples will be taken from patients with different liver disease aetiologies, including alcoholism and obesity, with a view on distinguishing the prevalent mutation types occurring in each disease context.\n\nWe will perform both whole genome and targeted sequencing, initially using the WTSI cancer panel. Later we aim to use a novel bait set that captures both cancer genes as well as genes relevant to the non-cancerous samples (ie. genes implicated in hereditary disorders, immune sequences).","abstract":"Recent work in the Campbell group has revealed somatic mutations present in normal, non-cancerous human skin. A subset of the mutations conferred selective advantages to the host cells, leading to clonal expansions and raising the risk for future cancer development. Capturing such somatic mutations in normal tissue is important to advance our understanding about carcinogenesis and could provide prospective medical insights. \n\nIn this project, our goal is to detect somatic mutations in normal (pre-cancerous) liver tissue. Using Laser Microdissection technology, we will dissect individual liver lobules from patient samples and submit these to sequencing. For each patient sample, we aim to sequence multiple lobules to characterise the mutagenic burden. Samples will be taken from patients with different liver disease aetiologies, including alcoholism and obesity, with a view on distinguishing the prevalent mutation types occurring in each disease context.\n\nWe will perform both whole genome and targeted sequencing, initially using the WTSI cancer panel. Later we aim to use a novel bait set that captures both cancer genes as well as genes relevant to the non-cancerous samples (ie. genes implicated in hereditary disorders, immune sequences).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-04T12:45:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002414","title":"ChIP Seq data of multiple myeloma and plasma cell leukaemia cell lines","description":"ChIP-seq data (H3K4Me1, H3K4Me3, H3K27Ac histone modifications) on multiple myeloma cell line KMS11 and plasma cell leukaemia cell lines L363 and JJN3","abstract":"ChIP-seq data (H3K4Me1, H3K4Me3, H3K27Ac histone modifications) on multiple myeloma cell line KMS11 and plasma cell leukaemia cell lines L363 and JJN3","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-04T17:21:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002415","title":"TRACERx 100: metastatic samples","description":"Whole exome sequencing of 10 metastatic biopsies from four TRACERx100 patients (see EGA dataset EGAS00001002247), collected either after relapse or death. The data from these samples are initially published with Abbosh, C. et al. Phylogenetic ctDNA analysis depicts early stage lung cancer evolution. Nature http://dx.doi.org/10.1038/nature22364 (2017).\n\nAbstract: \nEarlier detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a patient-specific approach to ctDNA profiling in the first 100 lung TRACERx (TRAcking Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release in early-stage non-small cell lung cancer and perform tumor volume limit of detection analyses. Through blinded profiling of post-operative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients destined to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastases, providing a new approach for ctDNA driven therapeutic studies.","abstract":"Whole exome sequencing of 10 metastatic biopsies from four TRACERx100 patients (see EGA dataset EGAS00001002247), collected either after relapse or death. The data from these samples are initially published with Abbosh, C. et al. Phylogenetic ctDNA analysis depicts early stage lung cancer evolution. Nature http://dx.doi.org/10.1038/nature22364 (2017).\n\nAbstract: \nEarlier detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a patient-specific approach to ctDNA profiling in the first 100 lung TRACERx (TRAcking Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release in early-stage non-small cell lung cancer and perform tumor volume limit of detection analyses. Through blinded profiling of post-operative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients destined to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastases, providing a new approach for ctDNA driven therapeutic studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-05T09:53:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002416","title":"WGS___Mutant_clone_mapping_in_normal_oesohagus_and_skin","description":"We will use whole genome sequencing to examine normal appearing oesophageal epithelium and skin to determine the mutational burden.  DNA will be extracted from epithelia of a defined size and we will overlay positional information from the epithelial pieces to give clone maps over a wide area.  This will be done in both oesophageal epithelium and skin","abstract":"We aim to assess the burden of mutant clones in normal human oesophagus, both of known driver oncogenic mutations and of mutants that drive clonal expansion but are not associated with cancer.  This will give insight into the earliest stages of cancer evolution.  As a comparator we will also examine abdominal skin from the same patient.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-05T14:48:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002417","title":"The_British_Autozygosity_Populations_BioResource","description":"This data set contains whole exome sequences of individuals with self-stated parental relatedness from the East London Genes &amp; Health cohort. Rare frequency functional variants in these healthy individuals will be studied with respect to the genetic health of the participants and loss-of-function analysis of human genes.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"This data set contains whole exome sequences of individuals with self-stated parental relatedness from the East London Genes &amp; Health cohort. Rare frequency functional variants in these healthy individuals will be studied with respect to the genetic health of the participants and loss-of-function analysis of human genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002418","title":"Exome sequencing of pseudomyxoma peritonei","description":"Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma mainly restricted to the peritoneal cavity and most commonly originating from the appendix. In this study, we sequenced whole coding genome of nine PMP tumors and paired normal tissues in order to identify commonly mutated genes and signaling pathways affected in PMP.","abstract":"Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma mainly restricted to the peritoneal cavity and most commonly originating from the appendix. In this study, we sequenced whole coding genome of nine PMP tumors and paired normal tissues in order to identify commonly mutated genes and signaling pathways affected in PMP.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-07T17:55:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002419","title":"Clinical and genetic analysis of a rare syndrome associated with neoteny","description":"We describe a novel syndrome in six patients with extreme developmental delay and the defining characteristic of neoteny. In an effort to discover any genetic causes of this syndrome whole genome sequence (WGS) analysis of the patients and their families was performed on Complete Genomics’ nanoarray platform.","abstract":"We describe a novel syndrome in six patients with extreme developmental delay and the defining characteristic of neoteny. In an effort to discover any genetic causes of this syndrome whole genome sequence (WGS) analysis of the patients and their families was performed on Complete Genomics’ nanoarray platform.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-07T21:13:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002420","title":"Whole genome sequencing identified biomarker of response to PD1 blockade in Natural-killer/T-cell lymphoma","description":"WGS data of 13 and TCS data of 8 NKTCL patients. Significant association of PD-L1 rearrangements with objective response to anti-PD1 (pembrolizumab).","abstract":"WGS data of 13 and TCS data of 8 NKTCL patients. Significant association of PD-L1 rearrangements with objective response to anti-PD1 (pembrolizumab).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-10T14:33:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002421","title":"CD36 defines CML cells less sensitive to imatinib","description":"Tyrosine kinase inhibitors (TKIs) are highly effective for treatment of chronic myeloid leukemia (CML), but very few patients are cured. Major drawbacks with TKIs are their low efficacy in eradicating the leukemic stem cells responsible for disease maintenance and relapse upon TKI cessation. Here, we performed RNA-sequencing of flow-sorted primitive (CD34+CD38low) and progenitor (CD34+CD38+) chronic phase CML cells and identified transcriptional upregulation of 32 cell surface molecules relative to corresponding normal bone marrow cells. Focusing on novel markers with increased expression on primitive CML cells, we confirmed upregulation of the scavenger receptor CD36 and the leptin receptor (LEPR) by flow cytometry. We also delineate a subpopulation of primitive CML cells expressing CD36 that is less sensitive to imatinib treatment. Using CD36 targeting antibodies, we show that the CD36 positive cells can be targeted and killed by antibody dependent cellular cytotoxicity (ADCC). In summary, CD36 defines a subpopulation of primitive CML cells with decreased imatinib sensitivity that can be effectively targeted by ADCC using an anti-CD36 antibody.","abstract":"Tyrosine kinase inhibitors (TKIs) are highly effective for treatment of chronic myeloid leukemia (CML), but very few patients are cured. Major drawbacks with TKIs are their low efficacy in eradicating the leukemic stem cells responsible for disease maintenance and relapse upon TKI cessation. Here, we performed RNA-sequencing of flow-sorted primitive (CD34+CD38low) and progenitor (CD34+CD38+) chronic phase CML cells and identified transcriptional upregulation of 32 cell surface molecules relative to corresponding normal bone marrow cells. Focusing on novel markers with increased expression on primitive CML cells, we confirmed upregulation of the scavenger receptor CD36 and the leptin receptor (LEPR) by flow cytometry. We also delineate a subpopulation of primitive CML cells expressing CD36 that is less sensitive to imatinib treatment. Using CD36 targeting antibodies, we show that the CD36 positive cells can be targeted and killed by antibody dependent cellular cytotoxicity (ADCC). In summary, CD36 defines a subpopulation of primitive CML cells with decreased imatinib sensitivity that can be effectively targeted by ADCC using an anti-CD36 antibody.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-10T15:37:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002422","title":"The genomic landscape of germinal center derived B-cell lymphomas other than follicular, diffuse-large B-cell and Burkitt lymphom","description":"As part of the ICGC, the ICGC MMML-Seq project performed whole genome sequencing and RNA sequencing of germinal center derived B-cell lymphoma. Analyses were performed in concordance with the guidelines of the ICGC.","abstract":"As part of the ICGC, the ICGC MMML-Seq project performed whole genome sequencing and RNA sequencing of germinal center derived B-cell lymphoma. Analyses were performed in concordance with the guidelines of the ICGC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-11T08:39:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002423","title":"Cisplatin increases sensitivity to FGFR inhibition in patient-derived xenograft models of lung squamous cell carcinoma","description":"Lung squamous cell carcinoma (SqCC) is a molecularly complex and genomically unstable disease. No targeted therapy is currently approved for lung SqCC, although potential oncogenic drivers of SqCC have been identified, including amplification of the fibroblast growth factor receptor 1 (FGFR1). Reports from a recently completed clinical trial indicate low response rates in patients treated with FGFR tyrosine kinase inhibitors, suggesting inadequacy of FGFR1 amplification as a biomarker of response, or the need for combination treatment. We aimed to develop accurate models of lung SqCC and determine improved targeted therapies for these tumors. We show that detection of FGFR1 mRNA by RNA in situ hybridisation is a better predictor of response to FGFR inhibition than FGFR1 gene amplification using clinically relevant patient-derived xenograft (PDX) models of lung SqCC. FGFR1-overexpressing tumors were observed in all histological subtypes of non-small cell lung cancers (NSCLC) as assessed on a tissue microarray, indicating a broader range of tumors that may respond to FGFR inhibitors. In FGFR1-overexpressing PDX tumors, we observed increased differentiation and reduced proliferation following FGFR inhibition. Combination therapy with cisplatin was able to increase tumor cell death, and dramatically prolonged animal survival compared to single agent treatment. Our data suggest that FGFR tyrosine kinase inhibitors can benefit NSCLC patients with FGFR1-overexpressing tumors and provides a rationale for clinical trials combining cisplatin with FGFR inhibitors.","abstract":"Lung squamous cell carcinoma (SqCC) is a molecularly complex and genomically unstable disease. No targeted therapy is currently approved for lung SqCC, although potential oncogenic drivers of SqCC have been identified, including amplification of the fibroblast growth factor receptor 1 (FGFR1). Reports from a recently completed clinical trial indicate low response rates in patients treated with FGFR tyrosine kinase inhibitors, suggesting inadequacy of FGFR1 amplification as a biomarker of response, or the need for combination treatment. We aimed to develop accurate models of lung SqCC and determine improved targeted therapies for these tumors. We show that detection of FGFR1 mRNA by RNA in situ hybridisation is a better predictor of response to FGFR inhibition than FGFR1 gene amplification using clinically relevant patient-derived xenograft (PDX) models of lung SqCC. FGFR1-overexpressing tumors were observed in all histological subtypes of non-small cell lung cancers (NSCLC) as assessed on a tissue microarray, indicating a broader range of tumors that may respond to FGFR inhibitors. In FGFR1-overexpressing PDX tumors, we observed increased differentiation and reduced proliferation following FGFR inhibition. Combination therapy with cisplatin was able to increase tumor cell death, and dramatically prolonged animal survival compared to single agent treatment. Our data suggest that FGFR tyrosine kinase inhibitors can benefit NSCLC patients with FGFR1-overexpressing tumors and provides a rationale for clinical trials combining cisplatin with FGFR inhibitors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-11T22:06:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002424","title":"Cell fate mapping of human glioblastoma reveals an invariant stem cell hierarchy pre- and post-treatment","description":"Human glioblastomas (GBMs) are thought to harbour a subpopulation of glioblastoma stem cells (GSCs) that initiate tumour formation and regrowth following treatment. However, the origin of their proliferative heterogeneity during tumour growth pre- and post-treatment remains poorly understood. Here we  study the clonal evolution of DNA barcoded GBMs following their serial propagation in xenograft mouse models to define the fate behaviour of individual GBM cells. Through quantitative analysis of clone sizes scored across multiple passages, we show that the growth of GBM clones in vivo are consistent with a remarkably neutral process resulting from a conserved proliferative hierarchy. In this model, slow-cycling stem-like cells give rise to a more rapidly cycling progenitor population with extensive self-maintenance capacity, that in turn generates short-lived cells that lack proliferative ability. We also identify rare \"outlier\" clones that deviate from these dynamics, and further show that chemotherapy reproducibly facilitates the selective expansion of pre-existing drug-resistant GBM lineages. Finally, we show that coexisting, functionally distinct GSCs may be targeted separately with epigenetic compounds. These findings show that, independent of an evolving mutational signature, the clonal dynamics of human GBM can be surprisingly robust, with intratumoural heterogeneity derived primarily from the defined stochastic fate behaviour of tumour cells within a conserved proliferative hierarchy.","abstract":"Human glioblastomas (GBMs) are thought to harbour a subpopulation of glioblastoma stem cells (GSCs) that initiate tumour formation and regrowth following treatment. However, the origin of their proliferative heterogeneity during tumour growth pre- and post-treatment remains poorly understood. Here we  study the clonal evolution of DNA barcoded GBMs following their serial propagation in xenograft mouse models to define the fate behaviour of individual GBM cells. Through quantitative analysis of clone sizes scored across multiple passages, we show that the growth of GBM clones in vivo are consistent with a remarkably neutral process resulting from a conserved proliferative hierarchy. In this model, slow-cycling stem-like cells give rise to a more rapidly cycling progenitor population with extensive self-maintenance capacity, that in turn generates short-lived cells that lack proliferative ability. We also identify rare \"outlier\" clones that deviate from these dynamics, and further show that chemotherapy reproducibly facilitates the selective expansion of pre-existing drug-resistant GBM lineages. Finally, we show that coexisting, functionally distinct GSCs may be targeted separately with epigenetic compounds. These findings show that, independent of an evolving mutational signature, the clonal dynamics of human GBM can be surprisingly robust, with intratumoural heterogeneity derived primarily from the defined stochastic fate behaviour of tumour cells within a conserved proliferative hierarchy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-11T22:24:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002425","title":"Whole Mitochondrial Sequencing of Gingivo-buccal Cancer: ICGC-India Project","description":"As a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India.   There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection. Detailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from blood and tumor tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai.  Whole genome and other sequencing experiments are being performed at the National Institute of Biomedical Genomics, Kalyani. Whole mitochondria sequencing of 89 patients was performed in this study. The mean depth of sequencing was at least 2500X, but variable across platforms, 2689X and 9894X for amplicon sequencing in Ion Torrent PGM (Tumor-blood pairs=16) and Illumina HiSeq 2500 (Tumor-blood pairs =48), respectively; and, 14,190X for whole genome sequencing in Illumina HiSeq 2500 (Tumor-blood pairs =25). Associations of mutation data with important clinical aspects have been found.","abstract":"As a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India.   There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection. Detailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from blood and tumor tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai.  Whole genome and other sequencing experiments are being performed at the National Institute of Biomedical Genomics, Kalyani. Whole mitochondria sequencing of 89 patients was performed in this study. The mean depth of sequencing was at least 2500X, but variable across platforms, 2689X and 9894X for amplicon sequencing in Ion Torrent PGM (Tumor-blood pairs=16) and Illumina HiSeq 2500 (Tumor-blood pairs =48), respectively; and, 14,190X for whole genome sequencing in Illumina HiSeq 2500 (Tumor-blood pairs =25). Associations of mutation data with important clinical aspects have been found.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-12T07:10:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002426","title":"Alternative_splicing_in_AML","description":"Acute myeloid leukaemia (AML) continues to have a very high mortality and its treatment has not changed for more than 20 years. Here, we propose to apply genomic-wide screens to directly identify therapeutic vulnerabilities of AML using AML cells lines with pre-defined somatic mutations. Our studies will be based on genome-wide CRISPR/CAs9 gRNA screens and will be used to identify drivers of drug resistance to standard chemotherapies.","abstract":"Acute myeloid leukaemia (AML) continues to have a very high mortality and its treatment has not changed for more than 20 years. Here, we propose to apply genomic-wide screens to directly identify therapeutic vulnerabilities of AML using AML cells lines with pre-defined somatic mutations. Our studies will be based on genome-wide CRISPR/CAs9 gRNA screens and will be used to identify drivers of drug resistance to standard chemotherapies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002427","title":"Renal_lesions__CAIX_","description":"Detection of early HIF-1 mutations with CA9 IHC in morphologically normal renal tubules","abstract":"Detection of early HIF-1 mutations with CA9 IHC in morphologically normal renal tubules","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002428","title":"A dataset compiled as a resource a for orthogonal assessment of exon CNV calling in NGS data","description":"The dataset includes high-quality sequencing data from a targeted NGS assay (the TruSight Cancer Panel) together with Multiplex Ligation-dependent Probe Amplification (MLPA) results for 96 independent samples. 66 samples contain at least one validated exon CNV and 30 samples have validated negative results for exon CNVs in 26 genes. The dataset includes 46 exon CNVs in BRCA1, BRCA2, TP53, MLH1, MSH2, MSH6, PMS2, EPCAM and PTEN, giving excellent representation of the cancer predisposition genes most frequently tested in clinical practice. Moreover, the validated exon CNVs include 25 single exon CNVs the most difficult exon CNV to detect. The full dataset includes FASTQ files, target BED file, and MLPA results.","abstract":"The dataset includes high-quality sequencing data from a targeted NGS assay (the TruSight Cancer Panel) together with Multiplex Ligation-dependent Probe Amplification (MLPA) results for 96 independent samples. 66 samples contain at least one validated exon CNV and 30 samples have validated negative results for exon CNVs in 26 genes. The dataset includes 46 exon CNVs in BRCA1, BRCA2, TP53, MLH1, MSH2, MSH6, PMS2, EPCAM and PTEN, giving excellent representation of the cancer predisposition genes most frequently tested in clinical practice. Moreover, the validated exon CNVs include 25 single exon CNVs the most difficult exon CNV to detect. The full dataset includes FASTQ files, target BED file, and MLPA results.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-18T08:52:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002429","title":"Tumor evolution of glioma intrinsic gene expression subtype associates with immunological changes in the microenvironment","description":"We leveraged IDH wild type glioblastomas, derivative neurospheres, and single cell gene expression profiles to define three tumor-intrinsic transcriptional subtypes designated as proneural, mesenchymal, and classical. Transcriptomic subtype multiplicity correlated with increased intratumoral heterogeneity and presence of tumor microenvironment. In silico cell sorting identified macrophages/microglia, CD4+ T lymphocytes, and neutrophils in the glioma microenvironment. NF1 deficiency resulted in increased tumor-associated macrophages/microglia infiltration. Longitudinal transcriptome analysis showed that expression subtype is retained in 55% of cases. Gene signature-based tumor microenvironment inference revealed a decrease in invading monocytes and a subtype-dependent increase in macrophages/microglia cells upon disease recurrence. Hypermutation at diagnosis or at recurrence associated with CD8+ T cell enrichment. Frequency of M2 macrophages detection associated with short-term relapse after radiation therapy.","abstract":"We leveraged IDH wild type glioblastomas, derivative neurospheres, and single cell gene expression profiles to define three tumor-intrinsic transcriptional subtypes designated as proneural, mesenchymal, and classical. Transcriptomic subtype multiplicity correlated with increased intratumoral heterogeneity and presence of tumor microenvironment. In silico cell sorting identified macrophages/microglia, CD4+ T lymphocytes, and neutrophils in the glioma microenvironment. NF1 deficiency resulted in increased tumor-associated macrophages/microglia infiltration. Longitudinal transcriptome analysis showed that expression subtype is retained in 55% of cases. Gene signature-based tumor microenvironment inference revealed a decrease in invading monocytes and a subtype-dependent increase in macrophages/microglia cells upon disease recurrence. Hypermutation at diagnosis or at recurrence associated with CD8+ T cell enrichment. Frequency of M2 macrophages detection associated with short-term relapse after radiation therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002430","title":"Deep single-cell RNA sequencing data for 12346 T cells from tumour, adjacent normal tissue and peripheral blood of treatment-naive NSCLC patients","description":"Cancer immunotherapies have shown sustained clinical responses in treating non-small cell lung cancer (NSCLC), but efficacy varies between patients and is believed to depend in part on the amount and properties of tumor infiltrating lymphocytes (TILs). To comprehensively depict and dissect the baseline landscape of the composition, lineage and functional states of TILs in lung cancer, here we generated deep single-cell RNA sequencing data for 12,346 T cells from the primary tumour, adjacent normal tissues and peripheral blood of 14 treatment-naive NSCLC patients. Combined expression and TCR-based lineage tracking revealed a significant proportion of effector T cells with common origins and similar functional states across peripheral blood and tumours pointing towards a highly migratory nature of these T cells. We also observed tumour-infiltrating CD8+ T cells undergoing extensive clonal expansion and exhaustion, with two clusters of cells exhibiting states preceding exhaustion. Survival analysis on independent datasets suggested that high ratio of pre-exhausted to exhausted T cells is associated with better prognosis of lung adenocarcinoma (LUAD). In addition, we observed further heterogeneity within the tumour regulatory T cells (Tregs), characterized by the bimodal distribution of TNFRSF9, an activation marker for antigen-specific Tregs. The gene signature of this group of activated tumour Tregs, which included IL1R2, correlated with poor prognosis in LUAD. The T cell clusters revealed by our single cell analyses provide a new approach for patient stratification, and the accompanying compendium of data will help the research community to gain further insight into the functional states and dynamics of T cell responses in lung cancer.","abstract":"Cancer immunotherapies have shown sustained clinical responses in treating non-small cell lung cancer (NSCLC), but efficacy varies between patients and is believed to depend in part on the amount and properties of tumor infiltrating lymphocytes (TILs). To comprehensively depict and dissect the baseline landscape of the composition, lineage and functional states of TILs in lung cancer, here we generated deep single-cell RNA sequencing data for 12,346 T cells from the primary tumour, adjacent normal tissues and peripheral blood of 14 treatment-naive NSCLC patients. Combined expression and TCR-based lineage tracking revealed a significant proportion of effector T cells with common origins and similar functional states across peripheral blood and tumours pointing towards a highly migratory nature of these T cells. We also observed tumour-infiltrating CD8+ T cells undergoing extensive clonal expansion and exhaustion, with two clusters of cells exhibiting states preceding exhaustion. Survival analysis on independent datasets suggested that high ratio of pre-exhausted to exhausted T cells is associated with better prognosis of lung adenocarcinoma (LUAD). In addition, we observed further heterogeneity within the tumour regulatory T cells (Tregs), characterized by the bimodal distribution of TNFRSF9, an activation marker for antigen-specific Tregs. The gene signature of this group of activated tumour Tregs, which included IL1R2, correlated with poor prognosis in LUAD. The T cell clusters revealed by our single cell analyses provide a new approach for patient stratification, and the accompanying compendium of data will help the research community to gain further insight into the functional states and dynamics of T cell responses in lung cancer.","study_type":"Other","pubmed_ids":[29942094],"external_links":null,"is_released":true,"released_date":"2017-04-19T02:04:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002431","title":"Neurodegenerative_TGS","description":"An investigation of clonal haematopoiesis in patients with neurodegenerative disease.","abstract":"The objective is to establish whether clonal haematopoiesis is associated with the development of Alzheimer's Disease, Parkinson's Disease and/or Multiple Sclerosis. Genomic DNA from peripheral blood will be analysed. RNA bait pulldown will be used to perform targeted sequencing of 41 genes known to be recurrently mutated in myeloid malignancies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-20T14:23:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002432","title":"The evolutionary trajectory of a highly recurrent paediatric high grade neuroepithelial tumour with MN1:BEND2 fusion","description":"Astroblastomas are rare brain tumours which predominate in children and young adults, and have a controversial claim as a distinct entity, with no established WHO grade. Reports suggest a better outcome than high grade gliomas, though they frequently recur. Recently, they have been described to overlap with a newly-discovered group of tumours described as ’high grade neuroepithelial tumour with MN1 alteration’ (CNS HGNET-MN1), defined by global methylation patterns and strongly associated with gene fusions targeting MN1. We have studied a unique case of astroblastoma arising in a 6 year old girl, with multiple recurrences over a period of 10 years, with the pathognomonic MN1:BEND2 fusion. Exome sequencing allowed for a phylogenetic reconstruction of tumour evolution, which when integrated with clinical, pathological and radiological data provide for a thorough understanding of disease progression, with initial treatment driving tumour dissemination along four distinct trajectories. Infiltration of distant sites was associated with a later genome doubling, whilst there was evidence of convergent evolution of different lesions acquiring distinct alterations targeting NF-κB. These data represent an usual opportunity to understand the evolutionary history of a highly recurrent childhood brain tumour, and provide novel therapeutic targets for astroblastoma / CNS HGNET-MN1.","abstract":"Astroblastomas are rare brain tumours which predominate in children and young adults, and have a controversial claim as a distinct entity, with no established WHO grade. Reports suggest a better outcome than high grade gliomas, though they frequently recur. Recently, they have been described to overlap with a newly-discovered group of tumours described as ’high grade neuroepithelial tumour with MN1 alteration’ (CNS HGNET-MN1), defined by global methylation patterns and strongly associated with gene fusions targeting MN1. We have studied a unique case of astroblastoma arising in a 6 year old girl, with multiple recurrences over a period of 10 years, with the pathognomonic MN1:BEND2 fusion. Exome sequencing allowed for a phylogenetic reconstruction of tumour evolution, which when integrated with clinical, pathological and radiological data provide for a thorough understanding of disease progression, with initial treatment driving tumour dissemination along four distinct trajectories. Infiltration of distant sites was associated with a later genome doubling, whilst there was evidence of convergent evolution of different lesions acquiring distinct alterations targeting NF-κB. These data represent an usual opportunity to understand the evolutionary history of a highly recurrent childhood brain tumour, and provide novel therapeutic targets for astroblastoma / CNS HGNET-MN1.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-21T14:14:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002433","title":"Genomic landscape of Chordoid Glioma","description":"Chordoid glioma (ChG) is a characteristic, slow growing and well-circumscribed diencephalic tumor, whose mutational landscape is unknown. We analyzed primary chordoid glioma samples by whole exome sequencing, RNAseq","abstract":"Chordoid glioma (ChG) is a characteristic, slow growing and well-circumscribed diencephalic tumor, whose mutational landscape is unknown. We analyzed primary chordoid glioma samples by whole exome sequencing, RNAseq","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-24T12:00:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002434","title":"Subclonal evolution of four ER+ breast cancers ascertained by WGS and scRNA-Seq","description":"We analyzed the subclonal evolution of four ER+ breast cancers over 2-15 years using whole-genome sequencing (WGS) and single-cell RNA-Seq (scRNA-Seq). For each patient we analyzed 2-6 cancer samples, generally metastatic pleural effusions, by WGS, along with germline DNA. Two of the samples per patient were selected for single-cell RNA-Seq.","abstract":"We analyzed the subclonal evolution of four ER+ breast cancers over 2-15 years using whole-genome sequencing (WGS) and single-cell RNA-Seq (scRNA-Seq). For each patient we analyzed 2-6 cancer samples, generally metastatic pleural effusions, by WGS, along with germline DNA. Two of the samples per patient were selected for single-cell RNA-Seq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002435","title":"SYK expression in monomorphic epitheliotropic intestinal T-cell lymphoma","description":"Monomorphic epitheliotropic intestinal T cell lymphoma (MEITL), formerly known as type II enteropathy associated T cell lymphoma (type II EATL), is a rare, aggressive primary intestinal T cell lymphoma with a poor prognosis and an incompletely understood pathogenesis. We collected 40 cases of MEITL and 27 cases of EATL, formerly known as type I EATL, and comparatively investigated the T cell receptor (TCR) itself and associated signaling molecules using immunohistochemistry, amplicon deep sequencing and bisulfite pyrosequencing. The TCR showed a frequent γδ T cell derivation in MEITL (55%) and overall a predominant positive TCR phenotype in MEITL (88%) compared to the mainly silent TCR phenotype in EATL (65%). The immunohistochemical expression of the spleen tyrosine kinase (SYK) turned out to be a distinctive feature of MEITL (95%) compared to EATL (0%). Aberrant SYK overexpression in MEITL is likely caused by hypomethylation of the SYK promoter, while no common mutations in the SYK gene or in its promoter could be detected. Using amplicon deep sequencing, mutations in DNMT3A, IDH2 and TET2 were infrequent events in MEITL and EATL. Immunohistochemical expression of linker for activation of T cells (LAT) subdivided MEITL into a LAT expressing subset (33%) and a LAT silent subset (67%) with a potentially earlier disease onset in LAT-positive MEITL.","abstract":"Monomorphic epitheliotropic intestinal T cell lymphoma (MEITL), formerly known as type II enteropathy associated T cell lymphoma (type II EATL), is a rare, aggressive primary intestinal T cell lymphoma with a poor prognosis and an incompletely understood pathogenesis. We collected 40 cases of MEITL and 27 cases of EATL, formerly known as type I EATL, and comparatively investigated the T cell receptor (TCR) itself and associated signaling molecules using immunohistochemistry, amplicon deep sequencing and bisulfite pyrosequencing. The TCR showed a frequent γδ T cell derivation in MEITL (55%) and overall a predominant positive TCR phenotype in MEITL (88%) compared to the mainly silent TCR phenotype in EATL (65%). The immunohistochemical expression of the spleen tyrosine kinase (SYK) turned out to be a distinctive feature of MEITL (95%) compared to EATL (0%). Aberrant SYK overexpression in MEITL is likely caused by hypomethylation of the SYK promoter, while no common mutations in the SYK gene or in its promoter could be detected. Using amplicon deep sequencing, mutations in DNMT3A, IDH2 and TET2 were infrequent events in MEITL and EATL. Immunohistochemical expression of linker for activation of T cells (LAT) subdivided MEITL into a LAT expressing subset (33%) and a LAT silent subset (67%) with a potentially earlier disease onset in LAT-positive MEITL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002436","title":"Subclonal evolution of four ER+ breast cancers determined by WGS and scRNA-Seq","description":"We analyzed the subclonal evolution of four ER+ breast cancers over 2-15 years using whole-genome sequencing (WGS) and single-cell RNA-Seq (scRNA-Seq). For each patient we analyzed 2-6 cancer samples, generally metastatic pleural effusions or ascites, by WGS, along with germline DNA. Two of the samples per patient were selected for single-cell RNA-Seq.","abstract":"We analyzed the subclonal evolution of four ER+ breast cancers over 2-15 years using whole-genome sequencing (WGS) and single-cell RNA-Seq (scRNA-Seq). For each patient we analyzed 2-6 cancer samples, generally metastatic pleural effusions or ascites, by WGS, along with germline DNA. Two of the samples per patient were selected for single-cell RNA-Seq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-25T16:04:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002437","title":"Integrative genomic and transcriptomic analysis of adult leiomyosarcoma (HIPO-028, HIPO-018, HIPO-021)","description":"Leiomyosarcoma (LMS) is an aggressive mesenchmyal malignancy with few therapeutic options. The mechanisms underlying LMS development, including clinically actionable genetic vulnerabilities, are largely unknown. We performed genomic and transcriptomic profiling of a large cohort of LMS tumors and identified substantial mutational heterogeneity, near-universal inactivation of TP53 and RB1, widespread DNA copy number alterations, chromothripsis, and frequent whole-genome duplication. Furthermore, we discovered recurrent alterations in telomere maintenance genes such as ATRX, RBL2, and RPA1, resulting in alternative lengthening of telomeres in 78% of cases. Finally, most tumors displayed hallmarks of “BRCAness”, including alterations in various homologous recombination DNA repair genes, multiple structural rearrangements, and enrichment of specific mutational signatures, and cultured LMS cells were sensitive towards olaparib and cisplatin treatment. This first comprehensive study of genetic alterations in LMS has uncovered key biological features that may inform future experimental research and enable the design of novel therapeutic strategies for this disease.","abstract":"Leiomyosarcoma (LMS) is an aggressive mesenchmyal malignancy with few therapeutic options. The mechanisms underlying LMS development, including clinically actionable genetic vulnerabilities, are largely unknown. We performed genomic and transcriptomic profiling of a large cohort of LMS tumors and identified substantial mutational heterogeneity, near-universal inactivation of TP53 and RB1, widespread DNA copy number alterations, chromothripsis, and frequent whole-genome duplication. Furthermore, we discovered recurrent alterations in telomere maintenance genes such as ATRX, RBL2, and RPA1, resulting in alternative lengthening of telomeres in 78% of cases. Finally, most tumors displayed hallmarks of “BRCAness”, including alterations in various homologous recombination DNA repair genes, multiple structural rearrangements, and enrichment of specific mutational signatures, and cultured LMS cells were sensitive towards olaparib and cisplatin treatment. This first comprehensive study of genetic alterations in LMS has uncovered key biological features that may inform future experimental research and enable the design of novel therapeutic strategies for this disease.","study_type":"Other","pubmed_ids":[5762758],"external_links":null,"is_released":true,"released_date":"2017-04-25T17:13:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002438","title":"Chracterising_cellur_pathways_underlying_CD3_CD28_activation_of_human_CD4__cells","description":"We devised an approach to disentangle the TCR and CD28 pathways upon stimulation in naive and memory primary human CD4+ T cells (Tcons) in response to defined stimulatory signals. Sorted Tcons were activated using a titration of anti-CD3 and anti-CD28 in combination as well as individually. As a control we cultured cells in the same conditions but without the stimuli. In total, we defined seven conditions from four individuals for sequencing.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Two signals are necessary for a successful T cell activation; interaction of the T cell receptor (TCR) with the major histocompatibility complex II (MHC) antigens on the antigen presenting cells (APC) and interaction of the CD28 receptor on the lymphocyte with B7 proteins presented by the APC.  The role of CD28 receptor in T cell activation remains poorly understood, with an ongoing debate on whether it amplifies TCR based signal, drives unique changes in the cell or whether it is neede at all for certain T cell subsets activation. Self-recognition by TCR can lead to autoimmunity, highlighting the importance to better study these pathways using genomics tools.\nWe aimed to decouple the T cell activation signals in order to better understand their role in immune response. I believe that by joining immunophenotyping with gene expression studies we can elucidate the pathways engaged by CD28 co-stimulation for a successful T cell activation in naive and memory cells. That will also allow us to explore the effect of increasing TCR signal in the differentiation of naive cells. Looking at gene expression variability between individuals, as well as their threshold response to a stimulus, we can gain an insight into the role of genetic variants in activation processes of CD4+ cells.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-26T10:56:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002439","title":"Whole exome sequencing in patients with ALS and concomitant FTD lacking the C9orf72 repeat expansion","description":"Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are part of a clinical, pathological and genetic continuum. The purpose of the present study was to assess the mutation burden that is present in ALS and/or FTD known disease-causing genes in 54 patients (16 with available postmortem neuropathological diagnosis) with concurrent ALS and FTD (ALS/FTD) not-carrying the C9orf72 hexanucleotide repeat expansion, the most important genetic cause in both diseases.","abstract":"Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are part of a clinical, pathological and genetic continuum. The purpose of the present study was to assess the mutation burden that is present in ALS and/or FTD known disease-causing genes in 54 patients (16 with available postmortem neuropathological diagnosis) with concurrent ALS and FTD (ALS/FTD) not-carrying the C9orf72 hexanucleotide repeat expansion, the most important genetic cause in both diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-26T11:33:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002440","title":"Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanconi anemia","description":"The WD40-containing E3 ubiquitin ligase RFWD3 has been recently linked to the repair of DNA damage by Homologous Recombination (HR). Here we show that an RFWD3 mutation within the WD40 domain is connected to the genetic disease Fanconi anemia (FA). An individual revealed congenital abnormalities characteristic for FA. Cells from the patient, carrying the compound heterozygous mutations c.205_206dupCC and c.1916T&gt;A in RFWD3, show increased sensitivity to DNA interstrand cross-linking agents in terms of increased chromosomal breakage, reduced survival and cell cycle arrest in G2 phase. The cellular phenotype is mirrored in genetically engineered human and avian cells by inactivation of RFWD3 or by introduction of the patient-derived missense mutation, and is rescued by expression of wildtype RFWD3 protein. HR is disrupted in RFWD3 mutant cells, caused by impaired relocation of mutant RFWD3 to chromatin and defective physical interaction with RPA. Rfwd3 knockout mice exhibit increased embryonic lethality, are sub-fertile, show ovarian and testicular atrophy and have a reduced life span in which they resemble other FA mouse models. Although mutation was detected in a single child with FA yet, we propose RFWD3 as a novel FA gene, FANCW, supported by cellular paradigm systems and an animal model.","abstract":"The WD40-containing E3 ubiquitin ligase RFWD3 has been recently linked to the repair of DNA damage by Homologous Recombination (HR). Here we show that an RFWD3 mutation within the WD40 domain is connected to the genetic disease Fanconi anemia (FA). An individual revealed congenital abnormalities characteristic for FA. Cells from the patient, carrying the compound heterozygous mutations c.205_206dupCC and c.1916T&gt;A in RFWD3, show increased sensitivity to DNA interstrand cross-linking agents in terms of increased chromosomal breakage, reduced survival and cell cycle arrest in G2 phase. The cellular phenotype is mirrored in genetically engineered human and avian cells by inactivation of RFWD3 or by introduction of the patient-derived missense mutation, and is rescued by expression of wildtype RFWD3 protein. HR is disrupted in RFWD3 mutant cells, caused by impaired relocation of mutant RFWD3 to chromatin and defective physical interaction with RPA. Rfwd3 knockout mice exhibit increased embryonic lethality, are sub-fertile, show ovarian and testicular atrophy and have a reduced life span in which they resemble other FA mouse models. Although mutation was detected in a single child with FA yet, we propose RFWD3 as a novel FA gene, FANCW, supported by cellular paradigm systems and an animal model.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-26T13:05:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002441","title":"Successful immune checkpoint blockade in a patient with advanced stage microsatellite unstable biliary tract cancer (H021)","description":"Cancers acquire multiple somatic mutations that can lead to the generation of immunogenic mutation-induced neoantigens. These neoantigens can be recognized by the host’s immune system. However, continuous stimulation of immune cells against tumor antigens can lead to immune cell exhaustion, which allows uncontrolled outgrowth of tumor cells. Recently, immune checkpoint inhibitors have emerged as a novel approach to overcome immune cell exhaustion and re-activate anti-tumor immune responses. In particular, antibodies blocking the exhaustion-mediating programmed death receptor (PD-1)/PD-L1 pathway have shown clinical efficacy. The effects were particularly pronounced in tumors with DNA mismatch repair deficiency and a high mutational load, which typically occur in the colon and  endometrium. Here, we report on a 24-year old woman diagnosed with extrahepatic cholangiocarcinoma who showed strong and durable response to the immune checkpoint inhibitor pembrolizumab, although treatment was initiated at an advanced stage of disease. The patient’s tumor displayed DNA mismatch repair deficiency and microsatellite instability (MSI), but lacked other features commonly discussed as predictors of response towards checkpoint blockade, such as PD-L1 expression or dense infiltration with cytotoxic T cells. Notably, high levels of HLA class I and II antigen expression were detected in the tumor, suggesting a potential causal relation between functionality of the tumor’s antigen presentation machinery and the success of immune checkpoint blockade. We suggest determining MSI status in combination with HLA class I and II antigen expression in tumors potentially eligible for immune checkpoint blockade even in the absence of conventional markers predictive for anti-PD-1/PD-L1 therapy and in entities not commonly linked to MSI phenotype. Further studies are required to determine the value of these markers for predicting the success of immune checkpoint blockade.  (H021)","abstract":"Cancers acquire multiple somatic mutations that can lead to the generation of immunogenic mutation-induced neoantigens. These neoantigens can be recognized by the host’s immune system. However, continuous stimulation of immune cells against tumor antigens can lead to immune cell exhaustion, which allows uncontrolled outgrowth of tumor cells. Recently, immune checkpoint inhibitors have emerged as a novel approach to overcome immune cell exhaustion and re-activate anti-tumor immune responses. In particular, antibodies blocking the exhaustion-mediating programmed death receptor (PD-1)/PD-L1 pathway have shown clinical efficacy. The effects were particularly pronounced in tumors with DNA mismatch repair deficiency and a high mutational load, which typically occur in the colon and  endometrium. Here, we report on a 24-year old woman diagnosed with extrahepatic cholangiocarcinoma who showed strong and durable response to the immune checkpoint inhibitor pembrolizumab, although treatment was initiated at an advanced stage of disease. The patient’s tumor displayed DNA mismatch repair deficiency and microsatellite instability (MSI), but lacked other features commonly discussed as predictors of response towards checkpoint blockade, such as PD-L1 expression or dense infiltration with cytotoxic T cells. Notably, high levels of HLA class I and II antigen expression were detected in the tumor, suggesting a potential causal relation between functionality of the tumor’s antigen presentation machinery and the success of immune checkpoint blockade. We suggest determining MSI status in combination with HLA class I and II antigen expression in tumors potentially eligible for immune checkpoint blockade even in the absence of conventional markers predictive for anti-PD-1/PD-L1 therapy and in entities not commonly linked to MSI phenotype. Further studies are required to determine the value of these markers for predicting the success of immune checkpoint blockade.  (H021)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-04-26T14:27:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002442","title":"Whole genome sequencing and whole exome sequencing of DIPG tumors and matched normal tissue","description":"Diffuse Intrinsic Pontine Glioma (DIPG) is a fatal brain cancer that arises in the brainstem of children with no effective treatment. To understand what drives DIPGs we integrated whole-genome-sequencing with methylation, expression and copy-number profiling.","abstract":"Diffuse Intrinsic Pontine Glioma (DIPG) is a fatal brain cancer that arises in the brainstem of children with no effective treatment. To understand what drives DIPGs we integrated whole-genome-sequencing with methylation, expression and copy-number profiling.","study_type":"Other","pubmed_ids":[24705254],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002443","title":"Transcriptional regulatory networks of tumor-associated macrophages that drive malignancy in mesenchymal glioblastoma","description":"Background: Glioblastoma (GBM) is a complex disease with extensive molecular and transcriptional heterogeneity. GBM can be subcategorized into four distinct subtypes; tumors that shift towards the mesenchymal phenotype upon recurrence are generally associated with treatment resistance, unfavorable prognosis, and the infiltration of pro-tumorigenic macrophages.\nResults: We explore the transcriptional regulatory networks of mesenchymal-associated tumor-associated macrophages (MA-TAMs), which drive the malignant phenotypic state of GBM, and identify macrophage receptor with collagenous structure (MARCO) as the most highly differentially expressed gene. MARCOhigh TAMs induce a phenotypic shift towards mesenchymal cellular state of glioma stem cells, promoting both invasive and proliferative activities, as well as therapeutic resistance to irradiation. MARCOhigh TAMs also significantly accelerate tumor engraftment and growth in vivo. Moreover, both MA-TAM master regulators and their target genes are significantly correlated with poor clinical outcomes, and are often associated with genomic aberrations in neurofibromin 1 (NF1) and phosphoinositide 3-kinases/mammalian target of rapamycin/Akt pathway (PI3K-mTOR-AKT)-related genes. We further demonstrate origination of MA-TAMs from peripheral blood, as well as their potential association\nwith tumor-induced polarization states and immunosuppressive environments.\nConclusions: Collectively, our study characterizes the global transcriptional profile of TAMs driving mesenchymal GBM pathogenesis, providing potential therapeutic targets for improving the effectiveness of GBM immunotherapy.","abstract":"Background: Glioblastoma (GBM) is a complex disease with extensive molecular and transcriptional heterogeneity. GBM can be subcategorized into four distinct subtypes; tumors that shift towards the mesenchymal phenotype upon recurrence are generally associated with treatment resistance, unfavorable prognosis, and the infiltration of pro-tumorigenic macrophages.\nResults: We explore the transcriptional regulatory networks of mesenchymal-associated tumor-associated macrophages (MA-TAMs), which drive the malignant phenotypic state of GBM, and identify macrophage receptor with collagenous structure (MARCO) as the most highly differentially expressed gene. MARCOhigh TAMs induce a phenotypic shift towards mesenchymal cellular state of glioma stem cells, promoting both invasive and proliferative activities, as well as therapeutic resistance to irradiation. MARCOhigh TAMs also significantly accelerate tumor engraftment and growth in vivo. Moreover, both MA-TAM master regulators and their target genes are significantly correlated with poor clinical outcomes, and are often associated with genomic aberrations in neurofibromin 1 (NF1) and phosphoinositide 3-kinases/mammalian target of rapamycin/Akt pathway (PI3K-mTOR-AKT)-related genes. We further demonstrate origination of MA-TAMs from peripheral blood, as well as their potential association\nwith tumor-induced polarization states and immunosuppressive environments.\nConclusions: Collectively, our study characterizes the global transcriptional profile of TAMs driving mesenchymal GBM pathogenesis, providing potential therapeutic targets for improving the effectiveness of GBM immunotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-02T04:21:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002444","title":"A combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancer","description":"The earlier diagnosis of cancer is one of the keys to reducing future cancer deaths.  Here we describe our efforts to develop a non-invasive, blood test for the detection of pancreatic ductal adenocarcinoma.  We combined blood tests for KRAS gene mutations with carefully thresholded protein biomarkers to determine whether the combination of these markers was superior to any single marker.  The cohort tested included 221 patients with resectable pancreatic ductal adenocarcinoma and 185 control patients without known cancers.  KRAS mutations were detected in the plasma of 66 patients (30%) and every mutation found in the plasma was identical to that subsequently found in the patients' primary tumor (100% concordance).  The use of KRAS in conjunction with two thresholded protein biomarkers (CA19-9 and prolactin) increased the sensitivity to 67%.  Only one of the 185 plasma samples from the control cohort were positive for any of the three markers (99.5% specificity).  This combinatorial approach may prove useful for the earlier detection of many cancer types.","abstract":"The earlier diagnosis of cancer is one of the keys to reducing future cancer deaths.  Here we describe our efforts to develop a non-invasive, blood test for the detection of pancreatic ductal adenocarcinoma.  We combined blood tests for KRAS gene mutations with carefully thresholded protein biomarkers to determine whether the combination of these markers was superior to any single marker.  The cohort tested included 221 patients with resectable pancreatic ductal adenocarcinoma and 185 control patients without known cancers.  KRAS mutations were detected in the plasma of 66 patients (30%) and every mutation found in the plasma was identical to that subsequently found in the patients' primary tumor (100% concordance).  The use of KRAS in conjunction with two thresholded protein biomarkers (CA19-9 and prolactin) increased the sensitivity to 67%.  Only one of the 185 plasma samples from the control cohort were positive for any of the three markers (99.5% specificity).  This combinatorial approach may prove useful for the earlier detection of many cancer types.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-02T07:08:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002445","title":"Control samples, breast cancer clinical samples and matched patient-derived tumour xenografts (PDTXs) to develop and test a computational approach to discriminate human and mouse sequences in PDTXs","description":"Patient-Derived Tumour Xenografts (PDTXs) have emerged as the pre-clinical models that best represent clinical tumour diversity and intra-tumour heterogeneity. The molecular characterization of PDTXs using High-Throughput Sequencing (HTS) is essential; however, the presence of mouse stroma is challenging for HTS data analysis. Indeed, the high homology between the two genomes results in a proportion of mouse reads being mapped as human. \nIn this study we generated Whole Exome Sequencing (WES) and RNA sequencing (RNA-seq) data from samples with known mixtures of mouse and human DNA or RNA.","abstract":"Patient-Derived Tumour Xenografts (PDTXs) have emerged as the pre-clinical models that best represent clinical tumour diversity and intra-tumour heterogeneity. The molecular characterization of PDTXs using High-Throughput Sequencing (HTS) is essential; however, the presence of mouse stroma is challenging for HTS data analysis. Indeed, the high homology between the two genomes results in a proportion of mouse reads being mapped as human. \nIn this study we generated Whole Exome Sequencing (WES) and RNA sequencing (RNA-seq) data from samples with known mixtures of mouse and human DNA or RNA.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-03T16:58:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002446","title":"Periprostatic tissue obtained from patients with from high-risk prostate cancer has a distinct transcriptional profile","description":"Increasing evidence indicates that altered adipose tissue homeostasis may be an important contributor to the development and/or progression of prostate cancer. As prostate tumours progress locally they frequently invade the periprostatic adipose compartment, gaining access to locally produced adipokines that have been associated with tumour cell growth, invasion and metastases. In this study we investigate the adipose transcriptional profiles of high-risk and low-risk disease to determine both prognostic potential and possible biological drivers of aggressive disease. RNA was extracted from periprostatic adipose tissue taken from patients categorised as having prostate cancer with either a high- or low-risk of progression by the D'Amico classification system and profiled by RNAseq. A clear separation was observed between the transcriptional profiles of high-risk and low-risk prostate cancer in periprostatic adipose tissue and a 17-gene signature consisting of IGHA1, SAA2, MYH11, DES, RERGL, SOCS3, PLA2G2A, SLC2A1, COL6A6, GPR34, CLDN1, PCDH10, SELE, ACAN, OLFM4, KLF5, KIF25, was able to separate high- and low-risk disease. Our results demonstrate that periprostatic adipose tissue is contributing to the tumour microenvironment of prostate cancer and affecting the progression of the disease.","abstract":"Increasing evidence indicates that altered adipose tissue homeostasis may be an important contributor to the development and/or progression of prostate cancer. As prostate tumours progress locally they frequently invade the periprostatic adipose compartment, gaining access to locally produced adipokines that have been associated with tumour cell growth, invasion and metastases. In this study we investigate the adipose transcriptional profiles of high-risk and low-risk disease to determine both prognostic potential and possible biological drivers of aggressive disease. RNA was extracted from periprostatic adipose tissue taken from patients categorised as having prostate cancer with either a high- or low-risk of progression by the D'Amico classification system and profiled by RNAseq. A clear separation was observed between the transcriptional profiles of high-risk and low-risk prostate cancer in periprostatic adipose tissue and a 17-gene signature consisting of IGHA1, SAA2, MYH11, DES, RERGL, SOCS3, PLA2G2A, SLC2A1, COL6A6, GPR34, CLDN1, PCDH10, SELE, ACAN, OLFM4, KLF5, KIF25, was able to separate high- and low-risk disease. Our results demonstrate that periprostatic adipose tissue is contributing to the tumour microenvironment of prostate cancer and affecting the progression of the disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002447","title":"Lymphoid_tissue_sequencing_study","description":"We intend to use single cell transcriptome analysis to explore the heterogenity of different cell types within the lymphoid organs","abstract":"We intend to use single cell transcriptome analysis to explore the heterogenity of different cell types within the lymphoid system.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002448","title":"Contribution of Genetic Variation and Developmental Stage to Methylome Dynamics in Myeloid Differentiation","description":"DNA methylation is important to establish a cell’s developmental identity. It also modulates cellular responses to endogenous developmental stimuli or environmental changes. We designed an in vitro myeloid differentiation model to analyze the genetic and developmental contribution to methylome dynamics using whole-genome bisulfide sequencing and transcriptome sequencing. Using a recursive partitioning approach, we identified 34,502 differentially methylated regions (DMRs) associated with genetic background and/or developmental stimuli. Specifically, 23,792 DMRs (69%) were significantly associated with inter-individual variations, of which 82% were associated with genetic polymorphisms in cis. Notably, inter-individual variations further modified 57 of 212 (26%) developmental DMRs with transcriptomic responses. Our study presents a novel analytical approach to determine the bona fide genetic contribution embedded in outlier patterns of CpG-SNPs in individual methylomes. This approach can be used to study genetic and epigenetic mechanisms underlying differential responses to developmental stimuli, environmental changes, and inter-individual differences in drug responses.","abstract":"DNA methylation is important to establish a cell’s developmental identity. It also modulates cellular responses to endogenous developmental stimuli or environmental changes. We designed an in vitro myeloid differentiation model to analyze the genetic and developmental contribution to methylome dynamics using whole-genome bisulfide sequencing and transcriptome sequencing. Using a recursive partitioning approach, we identified 34,502 differentially methylated regions (DMRs) associated with genetic background and/or developmental stimuli. Specifically, 23,792 DMRs (69%) were significantly associated with inter-individual variations, of which 82% were associated with genetic polymorphisms in cis. Notably, inter-individual variations further modified 57 of 212 (26%) developmental DMRs with transcriptomic responses. Our study presents a novel analytical approach to determine the bona fide genetic contribution embedded in outlier patterns of CpG-SNPs in individual methylomes. This approach can be used to study genetic and epigenetic mechanisms underlying differential responses to developmental stimuli, environmental changes, and inter-individual differences in drug responses.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002449","title":"Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics","description":"The human placenta is a dynamic and cellular heterogeneous organ, which is critical in fetomaternal homeostasis and the development of preeclampsia. Previous work has shown that placenta-derived cell-free RNA increases during pregnancy. We applied large-scale microfluidic single-cell transcriptomic technology to comprehensively characterize cellular heterogeneity of the human placentas and identified multiple placental cell-type–specific gene signatures. Analysis of the cellular signature expression in maternal plasma enabled noninvasive delineation of the cellular dynamics of the placenta during pregnancy and the elucidation of extravillous trophoblastic dysfunction in early preeclampsia.","abstract":"The human placenta is a dynamic and cellular heterogeneous organ, which is critical in fetomaternal homeostasis and the development of preeclampsia. Previous work has shown that placenta-derived cell-free RNA increases during pregnancy. We applied large-scale microfluidic single-cell transcriptomic technology to comprehensively characterize cellular heterogeneity of the human placentas and identified multiple placental cell-type–specific gene signatures. Analysis of the cellular signature expression in maternal plasma enabled noninvasive delineation of the cellular dynamics of the placenta during pregnancy and the elucidation of extravillous trophoblastic dysfunction in early preeclampsia.","study_type":"Other","pubmed_ids":[28830992],"external_links":null,"is_released":true,"released_date":"2017-05-05T09:48:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002450","title":"Mutations in SPINK2 induce azoospermia","description":"Azoospermia, characterized by the absence of spermatozoa in the ejaculate is a common cause of male infertility with a poorly characterized etiology. Exome sequencing analysis of two azoospermic brothers allowed the identification of a homozygous splice mutation in SPINK2, encoding a serine protease inhibitor believed to target acrosin, the main sperm acrosomal protease. In accord with these findings we observed that homozygous Spink2 KO male mice had azoospermia. Moreover, despite normal fertility, heterozygous male mice had a high rate of morphologically abnormal spermatozoa and a reduced sperm motility. Further analysis demonstrated that in the absence of Spink2, protease-induced stress initiates Golgi fragmentation and prevents acrosome biogenesis leading to spermatid differentiation arrest.  We also observed a deleterious effect of acrosin overexpression in HEK cells, effect that was alleviated by SPINK2 coexpression confirming its role as acrosin inhibitor. These results demonstrate that SPINK2 is necessary to neutralize proteases during their cellular transit towards the acrosome and that its deficiency induces a pathological continuum ranging from oligoasthenoteratozoospermia in heterozygotes to azoospermia in homozygotes.","abstract":"Azoospermia, characterized by the absence of spermatozoa in the ejaculate is a common cause of male infertility with a poorly characterized etiology. Exome sequencing analysis of two azoospermic brothers allowed the identification of a homozygous splice mutation in SPINK2, encoding a serine protease inhibitor believed to target acrosin, the main sperm acrosomal protease. In accord with these findings we observed that homozygous Spink2 KO male mice had azoospermia. Moreover, despite normal fertility, heterozygous male mice had a high rate of morphologically abnormal spermatozoa and a reduced sperm motility. Further analysis demonstrated that in the absence of Spink2, protease-induced stress initiates Golgi fragmentation and prevents acrosome biogenesis leading to spermatid differentiation arrest.  We also observed a deleterious effect of acrosin overexpression in HEK cells, effect that was alleviated by SPINK2 coexpression confirming its role as acrosin inhibitor. These results demonstrate that SPINK2 is necessary to neutralize proteases during their cellular transit towards the acrosome and that its deficiency induces a pathological continuum ranging from oligoasthenoteratozoospermia in heterozygotes to azoospermia in homozygotes.","study_type":"Other","pubmed_ids":[28554943],"external_links":null,"is_released":true,"released_date":"2017-05-05T13:08:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002451","title":"Somatic_mutation_and_clonal_evolution_in_the_human_pancreas","description":"In this study we aim to characterise the landscape of mutation and clonal selection in the human pancreas. The study combines targeted sequencing and whole-genome sequencing of microbiopsies from the pancreas. The range of patients studied will include healthy individuals, both smokers and non-smokers, and patients with pancreatic ductal adenocarcinoma.","abstract":"In this study we aim to characterise the landscape of mutation and clonal selection in the human pancreas. The study combines targeted sequencing and whole-genome sequencing of microbiopsies from the pancreas. The range of patients studied will include healthy individuals, both smokers and non-smokers, and patients with pancreatic ductal adenocarcinoma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002452","title":"Whole_genome_sequencing_of_100_DDD_trios_with_suspected_noncoding_causal_mutations","description":"We would like to whole-genome sequence 100 trios (300 individuals) from the DDD project in which we suspect the proband has a pathogenic noncoding mutation, to 30X coverage. These have been carefully selected to maximise the chances of finding pathogenic noncoding mutations. Specifically, we have selected probands who have no likely causal mutation within the coding region but who have a heterozygous loss-of-function mutation inherited from one parent in a known recessive developmental disorder gene, and whose phenotype is a good match for the typical phenotype caused by recessive variants in that gene. We suspect that these probands may have a heterozygous noncoding mutation on the other allele which reduces expression of the gene so that, together, these two mutations are effectively equivalent to a homozygous loss-of-function mutation. About a quarter of the probands have affected siblings and, if those siblings have been exome sequenced, we have checked that they are identical-by-descent in the region of the gene.  We propose to search in the promoter region, intronic and annotated regulatory regions around these genes of interest for rare variants inherited from the other parent (i.e. not the one who transmitted the loss-of-function variant), or de novo variants. If we find such variants, and demonstrate an enrichment of this compound heterozygous LoF noncoding mechanism above that expected by chance, we intend to follow up specific candidates by RNAseq and potentially CRISPR/Cas9 experiments.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"These are ~30X whole-genome sequence data from 100 trios from the DDD project. The offspring have heterogeneous developmental disorders (most have intellectual disability, and others have autism, seizures, heart defects etc.) and the parents are healthy. We suspect that these children have a noncoding mutation underlying their disorder, compound heterozygous with a loss-of-function mutation in a nearby gene.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-08T17:42:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002453","title":"Comprehensive Molecular Analysis of Colon Cancer for the Identification and Validation of New Biomarkers","description":"This study aims to identify diagnostic and prognostic biomarkers in colon cancer and to study understand the complex genomic, genetic and epigenetic relationships with a multiomic approach. The study includes tumor and paired normal mucosa of 100 colon cancer patients diagnosed at stage II, untreated and with microsatellite stable tumours. Also 50 normal mucosa samples from healthy donors are included as reference. The samples have been analysed for gene expression with Affymetrix U219 array (available at GEO GSE44076), SNP/CNV with the Affymetrix 6.0 Human SNP array, for DNA methylation with the Illumina 450K array. Small RNAs were sequenced with the Solid technology and 42 of the tumours and paired normal mucosa DNA were whole exome sequenced with Illumina Genome Analyzer.","abstract":"This study aims to identify diagnostic and prognostic biomarkers in colon cancer and to study understand the complex genomic, genetic and epigenetic relationships with a multiomic approach. The study includes tumor and paired normal mucosa of 100 colon cancer patients diagnosed at stage II, untreated and with microsatellite stable tumours. Also 50 normal mucosa samples from healthy donors are included as reference. The samples have been analysed for gene expression with Affymetrix U219 array (available at GEO GSE44076), SNP/CNV with the Affymetrix 6.0 Human SNP array, for DNA methylation with the Illumina 450K array. Small RNAs were sequenced with the Solid technology and 42 of the tumours and paired normal mucosa DNA were whole exome sequenced with Illumina Genome Analyzer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-09T11:05:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002454","title":"Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy","description":"Background: Genetic variation is an important determinant of RNA transcription and splicing, which in turn contributes to variation in human traits including cardiovascular diseases.Results: Here we report the first in-depth survey of heart transcriptome variation using RNA-sequencing in 149 (97)* patients with dilated cardiomyopathy and 113 (108)* non-diseased controls. We reveal extensive differences of gene expression and splicing between dilated cardiomyopathy patients and controls, affecting known as well as novel dilated cardiomyopathy genes. Moreover, we show a widespread effect of genetic variation on the regulation of transcription, isoform usage and allele specific expression. Systematic annotation of genome wide association SNPs identifies 60 functional candidate genes for heart phenotypes, representing 20% of all published heart genome wide association loci. Focusing on the dilated cardiomyopathy phenotype we found that eQTL variants are also enriched for dilated cardiomyopathy genome wide association signals in two independent cohorts.Conclusions: RNA transcription, splicing and allele specific expression are each important determinants of the DCM phenotype and are controlled by genetic factors. Our results represent a powerful resource for the field of cardiovascular genetics. (*) numbers in parentheses represent samples that the publication is based on.","abstract":"Background: Genetic variation is an important determinant of RNA transcription and splicing, which in turn contributes to variation in human traits including cardiovascular diseases.Results: Here we report the first in-depth survey of heart transcriptome variation using RNA-sequencing in 149 (97)* patients with dilated cardiomyopathy and 113 (108)* non-diseased controls. We reveal extensive differences of gene expression and splicing between dilated cardiomyopathy patients and controls, affecting known as well as novel dilated cardiomyopathy genes. Moreover, we show a widespread effect of genetic variation on the regulation of transcription, isoform usage and allele specific expression. Systematic annotation of genome wide association SNPs identifies 60 functional candidate genes for heart phenotypes, representing 20% of all published heart genome wide association loci. Focusing on the dilated cardiomyopathy phenotype we found that eQTL variants are also enriched for dilated cardiomyopathy genome wide association signals in two independent cohorts.Conclusions: RNA transcription, splicing and allele specific expression are each important determinants of the DCM phenotype and are controlled by genetic factors. Our results represent a powerful resource for the field of cardiovascular genetics. (*) numbers in parentheses represent samples that the publication is based on.","study_type":"Other","pubmed_ids":[28903782],"external_links":null,"is_released":true,"released_date":"2017-05-09T12:46:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002455","title":"Additional GBM longitudinal RNA-seq data for Dependency of glioblastoma on mesenchymal tumor cells - programmed macrophages for mesenchymal switching","description":"Additional RNA-seq data for GBM longitudinal patients","abstract":"Additional RNA-seq data for GBM longitudinal patients","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002456","title":"Overexpression_of_NPM1c_in_K562_cells","description":"Comparative gene expression analysis of K562 leukemia cell lines transfected with cDNAs expressing NPM1-TY1, NPM1cA-TY1 and TY1.","abstract":"Mutant NPM1 (NPM1c) is prevalent in approximately 50% of all karyotypically normal accute myeloid leukemia (NK-AML). We have studied the effects on gene expression in mouse models which carry the NPM1c mutation which are characterised by a specific gene expression signature of hox gene overexpression. In order to examine the effects on the proteome we have introduced NPM1 and NPM1c cDNA constructs into human leukemia cell line K562. These constructs have been tagged with the TY1 epitope in order to provide a distinguishable method in which to isolate exogenous expressed protein from endogenous NPM1 protein. Using these tagged constructs we have developed datasets which report the global effects of mutant NPM1c on the proteome as well as the effects on NPM1 protein intercators. These effects have been compared to alterations in gene expression identified by comparative RNAseq.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002457","title":"The demographic history and mutational load of African hunter-gatherers and farmers","description":"The distribution of deleterious genetic variation across human populations is a key issue in evolutionary biology and medical genetics. However, the impact of different modes of subsistence on recent changes in population size, patterns of gene flow, and deleterious mutational load remains unclear. Here, we report high-coverage exomes from various populations of rainforest hunter-gatherers and farmers from central Africa. We find that the recent demographic histories of hunter-gatherers and farmers differed considerably, with population collapses for hunter-gatherers and expansions for farmers, accompanied by increased gene flow. We show that purifying selection against newly arising deleterious alleles is of similar efficiency across African populations, in contrast with Europeans where we detect weaker purifying selection. Furthermore, the per-individual mutation load of rainforest hunter-gatherers is similar to that of farmers, under both additive and recessive models. Our results indicate that differences in the cultural practices and demographic regimes of African populations have not resulted in large differences in mutational burden, and highlight the beneficial role of gene flow in reshaping the distribution of deleterious genetic variation across human populations.","abstract":"The distribution of deleterious genetic variation across human populations is a key issue in evolutionary biology and medical genetics. However, the impact of different modes of subsistence on recent changes in population size, patterns of gene flow, and deleterious mutational load remains unclear. Here, we report high-coverage exomes from various populations of rainforest hunter-gatherers and farmers from central Africa. We find that the recent demographic histories of hunter-gatherers and farmers differed considerably, with population collapses for hunter-gatherers and expansions for farmers, accompanied by increased gene flow. We show that purifying selection against newly arising deleterious alleles is of similar efficiency across African populations, in contrast with Europeans where we detect weaker purifying selection. Furthermore, the per-individual mutation load of rainforest hunter-gatherers is similar to that of farmers, under both additive and recessive models. Our results indicate that differences in the cultural practices and demographic regimes of African populations have not resulted in large differences in mutational burden, and highlight the beneficial role of gene flow in reshaping the distribution of deleterious genetic variation across human populations.","study_type":"Other","pubmed_ids":[29531345],"external_links":null,"is_released":true,"released_date":"2017-05-10T13:53:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002458","title":"exome sequencing of GBM xenografts.","description":"Human glioblastomas (GBMs) are thought to harbour a subpopulation of glioblastoma stem cells (GSCs) that initiate tumour formation and regrowth following treatment [1-3]. However, the origin of their proliferative heterogeneity during tumour growth pre- and post-treatment remains poorly understood. Here we study the clonal evolution of DNA barcoded [4-6] GBMs following their serial propagation in xenograft mouse models to define the fate behaviour of individual GBM cells. Through quantitative analysis of clone sizes scored across multiple passages, we show that the growth of GBM clones in vivo is consistent with a remarkably neutral process resulting from a conserved proliferative hierarchy. In this model, slow-cycling stem-like cells give rise to a more rapidly cycling progenitor population with extensive self-maintenance capacity, that in turn generates short-lived cells that lack proliferative ability. We also identify rare “outlier” clones that deviate from these dynamics, and further show that chemotherapy reproducibly facilitates the selective expansion of pre-existing drug-resistant GBM lineages. Finally, we show that coexisting, functionally distinct GSCs may be targeted separately with epigenetic compounds. These findings suggest that, independent of an evolving mutational signature [7, 8], the clonal dynamics of human GBM can be surprisingly robust, with intratumoural heterogeneity derived primarily from the defined stochastic fate behaviour of tumour cells within a conserved proliferative hierarchy.","abstract":"Human glioblastomas (GBMs) are thought to harbour a subpopulation of glioblastoma stem cells (GSCs) that initiate tumour formation and regrowth following treatment [1-3]. However, the origin of their proliferative heterogeneity during tumour growth pre- and post-treatment remains poorly understood. Here we study the clonal evolution of DNA barcoded [4-6] GBMs following their serial propagation in xenograft mouse models to define the fate behaviour of individual GBM cells. Through quantitative analysis of clone sizes scored across multiple passages, we show that the growth of GBM clones in vivo is consistent with a remarkably neutral process resulting from a conserved proliferative hierarchy. In this model, slow-cycling stem-like cells give rise to a more rapidly cycling progenitor population with extensive self-maintenance capacity, that in turn generates short-lived cells that lack proliferative ability. We also identify rare “outlier” clones that deviate from these dynamics, and further show that chemotherapy reproducibly facilitates the selective expansion of pre-existing drug-resistant GBM lineages. Finally, we show that coexisting, functionally distinct GSCs may be targeted separately with epigenetic compounds. These findings suggest that, independent of an evolving mutational signature [7, 8], the clonal dynamics of human GBM can be surprisingly robust, with intratumoural heterogeneity derived primarily from the defined stochastic fate behaviour of tumour cells within a conserved proliferative hierarchy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002459","title":"Generation and comparison of CRISPR/Cas9 and Cre-mediated genetically engineered mouse models of sarcomaNote: This data is only available on ENA under the study ID 'PRJEB22279'. The link to the study is https://www.ebi.ac.uk/ena/data/search?query=PRJEB22279.","description":"Genetically engineered mouse models (GEMMs) that employ site-specific recombinase (SSR) technology are important tools for pre-clinical studies, but this approach is costly and time-consuming. Here, we show that the CRISPR/Cas9 system can be used to efficiently complement existing GEMMs of sarcoma and generate primary sarcomas in wild-type mice. Mice with the genotype KrasLSL-G12D/+; Rosa26LSL-Cas9-EGFP/+  received intramuscular delivery of an adenovirus expressing Cre recombinase and a single guide RNA (sgRNA) targeting Trp53. Cre-mediated expression of oncogenic Kras and Cas9, in combination with CRISPR/Cas9-mediated knockout of Trp53, was sufficient to generate primary soft tissue sarcomas. These tumors arose with kinetics and mutational load similar to those generated using the Cre-loxP system to activate oncogenic Kras and delete Trp53 alleles. Additionally, we injected an adenovirus containing Cas9 and sgRNAs targeting Nf1 and Trp53 into the sciatic nerve of wild-type mice. These mice formed malignant peripheral nerve sheath tumors (MPNSTs) in the same timeframe as MPNSTs generated using the Cre-loxP system to delete Nf1 and Ink4a/Arf alleles in GEMMs. These data demonstrate that CRISPR/Cas9 can be used to generate soft tissue sarcomas in wild-type mice.  Moreover, these results suggest that this technology can complement existing GEMMs for rapid assessment of tumor-modifying genes. These tools should decrease the time and expense associated with employing autochthonous mouse models of sarcoma for preclinical research.\n\nNote: This data is only available on ENA under the study ID \"PRJEB22279\". The link to the study is https://www.ebi.ac.uk/ena/data/search?query=PRJEB22279.","abstract":"Genetically engineered mouse models (GEMMs) that employ site-specific recombinase (SSR) technology are important tools for pre-clinical studies, but this approach is costly and time-consuming. Here, we show that the CRISPR/Cas9 system can be used to efficiently complement existing GEMMs of sarcoma and generate primary sarcomas in wild-type mice. Mice with the genotype KrasLSL-G12D/+; Rosa26LSL-Cas9-EGFP/+  received intramuscular delivery of an adenovirus expressing Cre recombinase and a single guide RNA (sgRNA) targeting Trp53. Cre-mediated expression of oncogenic Kras and Cas9, in combination with CRISPR/Cas9-mediated knockout of Trp53, was sufficient to generate primary soft tissue sarcomas. These tumors arose with kinetics and mutational load similar to those generated using the Cre-loxP system to activate oncogenic Kras and delete Trp53 alleles. Additionally, we injected an adenovirus containing Cas9 and sgRNAs targeting Nf1 and Trp53 into the sciatic nerve of wild-type mice. These mice formed malignant peripheral nerve sheath tumors (MPNSTs) in the same timeframe as MPNSTs generated using the Cre-loxP system to delete Nf1 and Ink4a/Arf alleles in GEMMs. These data demonstrate that CRISPR/Cas9 can be used to generate soft tissue sarcomas in wild-type mice.  Moreover, these results suggest that this technology can complement existing GEMMs for rapid assessment of tumor-modifying genes. These tools should decrease the time and expense associated with employing autochthonous mouse models of sarcoma for preclinical research.\n\nNote: This data is only available on ENA under the study ID \"PRJEB22279\". The link to the study is https://www.ebi.ac.uk/ena/data/search?query=PRJEB22279.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001002460","title":"SNP array data for the Milieu Intérieur cohort","description":"The Milieu Intérieur Consortium aims at identifying the environmental and genetic factors driving variation in innate and adaptive immune systems among healthy individuals. In the last four years, we combined standardized flow cytometric analysis of blood leukocytes, transcriptional profiles of whole blood after immune stimulation and genome-wide DNA genotyping in 1,000 healthy, unrelated donors of western European ancestry, to show that age, sex, as well as persistent infections and smoking, are the most important drivers of inter-individual differences in blood cell composition and transcriptional response to pathogens. The EGAS00001002460 study includes genotype data for 5,699,237 genotyped and imputed SNPs in the 816 healthy donors of the Milieu Intérieur cohort. Note that 184 of the 1,000 initial donors did not agree to share their data online.","abstract":"The Milieu Intérieur Consortium aims at identifying the environmental and genetic factors driving variation in innate and adaptive immune systems among healthy individuals. In the last four years, we combined standardized flow cytometric analysis of blood leukocytes, transcriptional profiles of whole blood after immune stimulation and genome-wide DNA genotyping in 1,000 healthy, unrelated donors of western European ancestry, to show that age, sex, as well as persistent infections and smoking, are the most important drivers of inter-individual differences in blood cell composition and transcriptional response to pathogens. The EGAS00001002460 study includes genotype data for 5,699,237 genotyped and imputed SNPs in the 816 healthy donors of the Milieu Intérieur cohort. Note that 184 of the 1,000 initial donors did not agree to share their data online.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-12T08:13:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002461","title":"Whole_Genome_Sequencing_of_INTERVAL","description":"15x Whole Genome Sequencing of 15,000 individuals from the INTERVAL study cohort, phase II.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"15x Whole Genome Sequencing of 15,000 individuals from the INTERVAL study cohort, phase II.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-12T12:49:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002462","title":"PCR-free HiSeqX whole genome sequence data on 120 samples with triplet repeat expansions (premutation and full expansions)","description":"Whole genome sequence (WGS) data was generated on 120 Coriell samples with the following validated repeat expansions: Fragile X Syndrome, Huntington disease, Friedreich’s ataxia, Amyotrophic Lateral Sclerosis, Myotonic Dystrophy, Spinocerebellar Ataxia 1/3 and Dentatorubral-Pallidoluysian Atrophy. These samples were sequenced using 2x150bp reads on an Illumina HiSeqX sequencer and the repeat expansions were called using ExpansionHunter to demonstrate the ability to call large repeats from high throughput, PCR-free WGS data.","abstract":"Whole genome sequence (WGS) data was generated on 120 Coriell samples with the following validated repeat expansions: Fragile X Syndrome, Huntington disease, Friedreich’s ataxia, Amyotrophic Lateral Sclerosis, Myotonic Dystrophy, Spinocerebellar Ataxia 1/3 and Dentatorubral-Pallidoluysian Atrophy. These samples were sequenced using 2x150bp reads on an Illumina HiSeqX sequencer and the repeat expansions were called using ExpansionHunter to demonstrate the ability to call large repeats from high throughput, PCR-free WGS data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-12T20:46:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002463","title":"ChIP-seq of GOF p53 mutants","description":"Gain-of-function TP53 mutations were detected in 41.3% of cases, in which co-occurring del(17p) underscored a dominant effect in &gt;25%. Missense mutations of TP53 clustered within the core DNA-binding domain, where R249S was most common. To explore the transcriptional effect of mutant p53(R249S), we performed chromatin immunoprecipitation-sequencing in the HCC cell line HKCI-11, which has a p53(R249S) mutation, and the human hepatocyte line MIHA, which is p53(WT). The results revealed distinct binding profiles between wildtype p53 and p53 mutant.","abstract":"Gain-of-function TP53 mutations were detected in 41.3% of cases, in which co-occurring del(17p) underscored a dominant effect in &gt;25%. Missense mutations of TP53 clustered within the core DNA-binding domain, where R249S was most common. To explore the transcriptional effect of mutant p53(R249S), we performed chromatin immunoprecipitation-sequencing in the HCC cell line HKCI-11, which has a p53(R249S) mutation, and the human hepatocyte line MIHA, which is p53(WT). The results revealed distinct binding profiles between wildtype p53 and p53 mutant.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-13T05:04:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002464","title":"ATAC_seq_Profiling_of_Immune_Cells_from_the_gut_and_blood","description":"We recently published a manuscript in Gut comparing gene expression signatures in CD4+ and CD8+ T Cells from the blood and from 2 tissues in the gut (the intestinal epithelial and lamina propria). We now wish to extend our functional profiling of immune cells relevant to immune-mediated diseases of the intestine (such as IBD) by performing ATAC-seq assays of open-chromatin across a series of tissues from the blood and gut. Across individuals we have sampled tissue from two different gut locations and from the blood. At both gut locations we have sorted three different lymphocyte populations from both intestinal epithelia and the lamina propria. From the blood, we have sorted six different lymphocyte populations, including the three that were ascertained from the intestinal samples. The ATAC assay has been performed across each of these separated cell populations and yielded libraries for sequencing. To test the robustness of the assay we have also performed a series of 'validation' experiments involving four independent individuals. Each individual had blood drawn at two independent time points, both of which were then separated into two aliquots for assessment of te\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"We are looking to extend our functional profiling of immune cells relevant to immune-mediated diseases of the intestine (such as IBD) by performing ATAC-seq assays of open-chromatin across a series of tissues from the blood and gut.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002465","title":"AGR_Project___African_Genome_Resource__total_RNA_sequencing_for_1000_Genomes_African_populations","description":"GWAS by developing large scale sequencing resources among African populations for imputation and fine mapping, the AGR will in parallel develop and curate resources to interpret identified associations in African populations, given that a substantial number of genetic associations arise from population specific variation (Gurdasani et al, Nature (under review)). Using 1000 genomes cell lines, we will generate high coverage RNAseq data (Illumina HiSeq) from 6 different populations across Africa; the first large-scale resource to examine eQTLs within Africa. Specifically we intend to sequence transcriptomes from 600 unrelated individuals from six populations from West (Gambian, The Gambia; Mende, Sierra Leone; Esan and Yoruba, Nigeria) and East Africa (Luhya and Masai, Kenya). This resource will help understand the transcriptional landscape in African populations, population differences in the diversity of splicing isoforms, as well as identify novel transcripts and exons across the genome. Such a tool will be invaluable for the interpretation of findings from large-scale GWAS being conducted in Africa, supporting initiatives such as the H3A consortium.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"As part of the African Genome Resource (AGR) project we aim to create an African transcriptome panel. Using 1000 genomes cell lines, we generated high coverage RNAseq data (Illumina HiSeq) from 6 different populations across Africa; the first large-scale resource to examine eQTLs within Africa. Specifically we sequenced transcriptomes from 600 unrelated individuals from six populations from West (Gambian, The Gambia; Mende, Sierra Leone; Esan and Yoruba, Nigeria) and East Africa (Luhya and Masai, Kenya). Such a resource will help understand the transcriptional landscape in African populations, population differences in the diversity of splicing isoforms, as well as identify novel transcripts and exons across the genome.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002466","title":"GDAP_Zulu_WG_TGS","description":"We will sequence the whole genome of a Zulu cell line using a combination of BioNano (2 enzymes), PacBio (50x), 10XGenomics Chromium and Illumina HiseqX (30x) platforms.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Using a range of next-generation sequencing and library making technologies, we aim to build a HLA data resource for Africa. This resource includes HLA genomic regional sequences for individuals from representative populations across Africa as well as high coverage (50x) representative African whole genomes mapped de-novo.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002467","title":"Genome_Diversity_in_Africa_Project__Mende","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region. The Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group). Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002468","title":"Genome_Diversity_in_Africa_Project__Esan","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region. The Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group). Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002469","title":"Genome_Diversity_in_Africa_Project__Luhya","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region. The Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group). Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002470","title":"Genome_Diversity_in_Africa_Project__Yoruba","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region. The Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group). Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002471","title":"Mutational_signatures_and_clonal_dynamics_in_normal_human_tissues","description":"Somatic mutations (burdens and signatures) and clonal dynamics in normal human tissues","abstract":"The aim of this project is to investigate somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues using a cell type specific approach. We are utilising laser capture microscopy to idnetifiy and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-16T14:39:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002472","title":"CINECA synthetic data.Please note: This study contains synthetic data (with cohort “participants” / ”subjects” marked with FAKE) has no identifiable data and cannot be used to make any inference about cohort data or results.","description":"Please note: This study contains synthetic data (with cohort “participants” / ”subjects” marked with FAKE) has no identifiable data and cannot be used to make any inference about cohort data or results. The purpose of this dataset is to aid development of technical implementations for cohort data discovery, harmonization, access, and federated analysis. In support of FAIRness in data sharing, this dataset  is made freely available under the Creative Commons Licence (CC-BY). Please ensure this preamble is included with this dataset and that the  CINECA project (funding: EC H2020 grant 825775) is acknowledged. For any questions please contact isuru@ebi.ac.uk or cthomas@ebi.ac.uk","abstract":"Please note: This study contains synthetic data (with cohort “participants” / ”subjects” marked with FAKE) has no identifiable data and cannot be used to make any inference about cohort data or results. The purpose of this dataset is to aid development of technical implementations for cohort data discovery, harmonization, access, and federated analysis. In support of FAIRness in data sharing, this dataset  is made freely available under the Creative Commons Licence (CC-BY). Please ensure this preamble is included with this dataset and that the  CINECA project (funding: EC H2020 grant 825775) is acknowledged. For any questions please contact isuru@ebi.ac.uk or cthomas@ebi.ac.uk","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-16T16:15:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002473","title":"Fungal infection in neural tissue from Amyotrophic Lateral Sclerosis","description":"The study shows that fungus infection, isolated from neural tissue, can be a risk factor to develop Amyothophic lateral sclerosis (ALS).","abstract":"The study shows that fungus infection, isolated from neural tissue, can be a risk factor to develop Amyothophic lateral sclerosis (ALS).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-17T08:45:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002474","title":"Genomic_profiling_of_B_other_Adult_ALL_WGS","description":"Adult ALL is an aggressive leukaemia, affecting adults of all ages. It is associated with a rapid onset and poor outcomes.  Our understanding of adult ALL genome has been limited to molecular markers first described in paediatric ALL and validated in adult ALL and to date there have been no studies investigating the genomics of Adult ALL. We will perform whole genome sequencing on at least 100 Adult ALL cases. Priority will be given on ALL cases without a known primary lesion by cytogenetic analysis which are categorised as “B-other”.  We will also sequence representative cases of each known subtype. This will deliver a comprehensive annotation of the genomic landscape of Adult ALL to include acquired somatic mutations (substitutions, indels, structural variants/fusion genes) and copy number profiles. The focus on B-other Adult ALL is likely to result in new and previously undescribed genomic lesions.","abstract":"Adult ALL is an aggressive leukaemia, affecting adults of all ages. It is associated with a rapid onset and poor outcomes.  Our understanding of adult ALL genome has been limited to molecular markers first described in paediatric ALL and validated in adult ALL and to date there have been no studies investigating the genomics of Adult ALL. We will perform whole genome sequencing on at least 100 Adult ALL cases. Priority will be given on ALL cases without a known primary lesion by cytogenetic analysis which are categorised as “B-other”.  We will also sequence representative cases of each known subtype. This will deliver a comprehensive annotation of the genomic landscape of Adult ALL to include acquired somatic mutations (substitutions, indels, structural variants/fusion genes) and copy number profiles. The focus on B-other Adult ALL is likely to result in new and previously undescribed genomic lesions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-17T09:07:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002475","title":"Identification of fusion transcripts by RNA-sequencing and Whole genome sequencing of a METABRIC patient sample","description":"Fusion transcripts and their exact breakpoints were identified in RNA-seq data (30X) of an ER-,HER2+ breast cancer. DNA-level breakpoints associated with the fusion events were determined by analyzing whole genome sequencing (WGS) data (30X) from the same donor. The RNA-seq and WGS data for this case were generated on the Illumina platform using standard protocols. The patient (MB-0152) derives from the METABRIC cohort for which array based copy number and gene expression data were previously described (EGAS00000000083).","abstract":"Fusion transcripts and their exact breakpoints were identified in RNA-seq data (30X) of an ER-,HER2+ breast cancer. DNA-level breakpoints associated with the fusion events were determined by analyzing whole genome sequencing (WGS) data (30X) from the same donor. The RNA-seq and WGS data for this case were generated on the Illumina platform using standard protocols. The patient (MB-0152) derives from the METABRIC cohort for which array based copy number and gene expression data were previously described (EGAS00000000083).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-18T05:54:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002476","title":"Predictor_Pandora_Ovarian_Xenograft","description":"This study will look at mutational profiles of xenografts (derived from ovarian cancer patients) treated with chemotherapy, and that have developed resistance to treatment.","abstract":"This study will look at mutational profiles of xenografts (derived from ovarian cancer patients) treated with chemotherapy, and that have developed resistance to treatment.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002477","title":"GENOMIC INSTABILITY IN MISMATCH REPAIR DEFICIENT COLORECTAL CANCER","description":"Here we performed whole exome sequencing on a series of 47 mismatch repair (MMR) deficient colorectal cancers (CRC) in order to identified key events in tumoral initiation and progression","abstract":"Here we performed whole exome sequencing on a series of 47 mismatch repair (MMR) deficient colorectal cancers (CRC) in order to identified key events in tumoral initiation and progression","study_type":"Other","pubmed_ids":[30116770],"external_links":null,"is_released":true,"released_date":"2017-05-18T15:32:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002478","title":"Cell motility and migration as determinants of stem cell efficacy","description":"Limited stem cell migration capacities and undirected homing hamper their therapeutic efficacy. We report here the novel technology to isolate stem cell subpopulations with high migration potential. Hereby, we identified podoplanin-dependent stem cell mobility as important mechanism for their in vivo homing capacities and therapeutic efficacy as validated in preclinical models of Alzheimer´s disease and mouse glioma. In vivo applications of highly migrating stem cells resulted in remarkable improvement of targeted homing and engraftment rates. Moreover, animals receiving highly migrating stem cells showed higher recovery rates compared to unselected stem cells. This novel technology provides useful tool to improve therapeutic efficacy of stem cells and give insights into stem cell subpopulations heterogeneity with the potential of general applicability for cellular therapies.","abstract":"Limited stem cell migration capacities and undirected homing hamper their therapeutic efficacy. We report here the novel technology to isolate stem cell subpopulations with high migration potential. Hereby, we identified podoplanin-dependent stem cell mobility as important mechanism for their in vivo homing capacities and therapeutic efficacy as validated in preclinical models of Alzheimer´s disease and mouse glioma. In vivo applications of highly migrating stem cells resulted in remarkable improvement of targeted homing and engraftment rates. Moreover, animals receiving highly migrating stem cells showed higher recovery rates compared to unselected stem cells. This novel technology provides useful tool to improve therapeutic efficacy of stem cells and give insights into stem cell subpopulations heterogeneity with the potential of general applicability for cellular therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-18T16:01:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002479","title":"Genome-wide DNA methylation profiles of NSCLC xenograft and primary lung tissues for the identification of epigenetic predictive biomarkers.","description":"Non-small cell lung cancers (NSCLC) are the most common cause of cancer-related deaths worldwide and primarily treated with platinum-based drugs like cisplatin and carboplatin, radiation and surgery. The major challenge in the management of NSCLC are intrinsic or acquired resistance mechanisms with only few published molecular markers which can predict the outcome of the patients. On the other side, changes in DNA methylation are observed in nearly all cancer types making them suitable as biomarker. Here genome-wide methylation profiles from MeDIP-Seq  and gene expression profiling data  of 22  primary NSCLC, adjacent normal tissue and PDX samples are provided. For each PDX tumor growth rates were measured in absence or presence of chemotherapy.","abstract":"Non-small cell lung cancers (NSCLC) are the most common cause of cancer-related deaths worldwide and primarily treated with platinum-based drugs like cisplatin and carboplatin, radiation and surgery. The major challenge in the management of NSCLC are intrinsic or acquired resistance mechanisms with only few published molecular markers which can predict the outcome of the patients. On the other side, changes in DNA methylation are observed in nearly all cancer types making them suitable as biomarker. Here genome-wide methylation profiles from MeDIP-Seq  and gene expression profiling data  of 22  primary NSCLC, adjacent normal tissue and PDX samples are provided. For each PDX tumor growth rates were measured in absence or presence of chemotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-22T11:40:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002480","title":"The link between centrosome cohesion defects and genome instability unveiled by CROCC deficiency in lethal human cancers","description":"The century-old hypothesis on the role of centrosome in cancer remains unresolved. We show that reduced dosage of CROCC, a centrosomal-linker component required for centrosome cohesion and separation, due to mutation or allelic loss at 1p36.13 results in impaired centrosome phenotypes and monopolar mitotic forms characterizing a lethal subset of human colorectal cancers with rhabdoid phenotype. Interfering with CROCC in near-diploid colon cancer cells disrupts bipolar mitotic spindle architecture, and causes unequal DNA segregation errors to daughter cells resulting in a highly aggressive rhabdoid-like phenotype in vitro. Conversely, CROCC restoration in a metastatic cellular model harboring 1p36.13 deletion results in correction of centrosome segregation errors and cell death, revealing a mechanism of tolerance to gross mitotic errors and tetraploidization, two hallmarks of chromosomal instability. Our data shed light on a previously unknown link between centrosome cohesion apparatus and lethal cancer phenotypes providing new insight into pathways underlying genome instability.","abstract":"The century-old hypothesis on the role of centrosome in cancer remains unresolved. We show that reduced dosage of CROCC, a centrosomal-linker component required for centrosome cohesion and separation, due to mutation or allelic loss at 1p36.13 results in impaired centrosome phenotypes and monopolar mitotic forms characterizing a lethal subset of human colorectal cancers with rhabdoid phenotype. Interfering with CROCC in near-diploid colon cancer cells disrupts bipolar mitotic spindle architecture, and causes unequal DNA segregation errors to daughter cells resulting in a highly aggressive rhabdoid-like phenotype in vitro. Conversely, CROCC restoration in a metastatic cellular model harboring 1p36.13 deletion results in correction of centrosome segregation errors and cell death, revealing a mechanism of tolerance to gross mitotic errors and tetraploidization, two hallmarks of chromosomal instability. Our data shed light on a previously unknown link between centrosome cohesion apparatus and lethal cancer phenotypes providing new insight into pathways underlying genome instability.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002481","title":"CNV detection in targeted NGS panel data","description":"The aim of this study was to compare copy-number-variation (CNV) detection methods for targeted NGS panel data in a clinical diagnostic setting. We present targeted NGS panel data from 170 samples that were processed using the TruSight(TM) Cancer (TSC) panel (Illumina, San Diego, CA, USA), which targets 94 genes and 284 SNPs associated with a predisposition towards cancer. The samples are enriched for CNVs in the genes of interest. All CNVs have previously been assessed with MLPA and can therefore be considered as confirmed.","abstract":"The aim of this study was to compare copy-number-variation (CNV) detection methods for targeted NGS panel data in a clinical diagnostic setting. We present targeted NGS panel data from 170 samples that were processed using the TruSight(TM) Cancer (TSC) panel (Illumina, San Diego, CA, USA), which targets 94 genes and 284 SNPs associated with a predisposition towards cancer. The samples are enriched for CNVs in the genes of interest. All CNVs have previously been assessed with MLPA and can therefore be considered as confirmed.","study_type":"Other","pubmed_ids":[28449315],"external_links":null,"is_released":true,"released_date":"2017-05-23T09:40:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002482","title":"H3Africa - Genomic and Environmental Risk Factors for Cardiometabolic Disease in Africans","description":"The long-term vision of the AWI-Gen Collaborative Centre (CC) is to build sustainable capacity in Africa for research that leads to an understanding of the interplay between genetic, epigenetic and environmental risk factors for obesity and related cardiometabolic diseases (CMD) in sub-Saharan Africa. The CC will be consolidated under the auspices of the University of the Witwatersrand (Wits) and the International Network for the Demographic Evaluation of Populations and Their Health in Developing Countries (INDEPTH). It will capitalize on the unique strengths of existing longitudinal cohorts, including the urban Soweto and rural Agincourt studies in South Africa (Wits based), and the well established INDEPTH demographic health and surveillance centers in Kenya, Ghana, Burkina Faso and South Africa. The centers offer established infrastructure, trained fieldworkers, long-standing community engagement, and detailed longitudinal phenotypic data, focusing on obesity and cardiometabolic health. Key strengths are harmonized phenotyping across sites, building on strong existing cohorts, and representation of the geographic and social variability of African populations. We aim to: 1. Build sustainable infrastructure (biobanks and laboratories) and capabilities (well characterized population cohorts, genotyping and bioinformatics) for genomic research on the African continent; 2. Understand the genomic architecture of sub-Saharan populations from west, east and south Africa to guide genomic studies (genome sequencing and high throughput SNP and CNV arrays using unrelated individuals and family trios to improve the accuracy of haplotype analyses) and; 3. Investigate the independent and synergistic genomic contributions to body fat distribution (BMI, hip/waist circumference, subcutaneous and visceral fat) in these populations considering the relevant environmental and social contexts (rural/urban communities, quickly transitioning obesity prevalence, differential HIV, TB, and malaria infection histories). We will investigate the effect of obesity and fat distribution on the risk for CMD in the longitudinal cohorts.","abstract":"The long-term vision of the AWI-Gen Collaborative Centre (CC) is to build sustainable capacity in Africa for research that leads to an understanding of the interplay between genetic, epigenetic and environmental risk factors for obesity and related cardiometabolic diseases (CMD) in sub-Saharan Africa. The CC will be consolidated under the auspices of the University of the Witwatersrand (Wits) and the International Network for the Demographic Evaluation of Populations and Their Health in Developing Countries (INDEPTH). It will capitalize on the unique strengths of existing longitudinal cohorts, including the urban Soweto and rural Agincourt studies in South Africa (Wits based), and the well established INDEPTH demographic health and surveillance centers in Kenya, Ghana, Burkina Faso and South Africa. The centers offer established infrastructure, trained fieldworkers, long-standing community engagement, and detailed longitudinal phenotypic data, focusing on obesity and cardiometabolic health. Key strengths are harmonized phenotyping across sites, building on strong existing cohorts, and representation of the geographic and social variability of African populations. We aim to: 1. Build sustainable infrastructure (biobanks and laboratories) and capabilities (well characterized population cohorts, genotyping and bioinformatics) for genomic research on the African continent; 2. Understand the genomic architecture of sub-Saharan populations from west, east and south Africa to guide genomic studies (genome sequencing and high throughput SNP and CNV arrays using unrelated individuals and family trios to improve the accuracy of haplotype analyses) and; 3. Investigate the independent and synergistic genomic contributions to body fat distribution (BMI, hip/waist circumference, subcutaneous and visceral fat) in these populations considering the relevant environmental and social contexts (rural/urban communities, quickly transitioning obesity prevalence, differential HIV, TB, and malaria infection histories). We will investigate the effect of obesity and fat distribution on the risk for CMD in the longitudinal cohorts.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-24T12:00:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002483","title":"Hip OA Functional Genomics","description":"The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of hip  osteoarthritis that culminates in the need for total joint replacement (TJR). This study is a feasibility pilot that integrates functional genomics data from diseased and non-diseased tissues of OA patients who have undergone TJR. For each tissue, we characterised epigenetic marks (methylation), gene transcription (RNASeq) and expression (quantitative proteomics). We also generated genotype data on the HumanCoreExome array for each individual.","abstract":"The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of hip  osteoarthritis that culminates in the need for total joint replacement (TJR). This study is a feasibility pilot that integrates functional genomics data from diseased and non-diseased tissues of OA patients who have undergone TJR. For each tissue, we characterised epigenetic marks (methylation), gene transcription (RNASeq) and expression (quantitative proteomics). We also generated genotype data on the HumanCoreExome array for each individual.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-24T16:26:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002484","title":"RRBS sequencing of 7 tumour regions and a normal sample from a single TRACERx patient.","description":"Background: Epigenetic heterogeneity within a tumour can play an important role in tumour evolution and the emergence of resistance to treatment. It is increasingly recognised that the study of DNA methylation (DNAm) patterns along the genome - so-called `epialleles' - offers greater insight into epigenetic dynamics than conventional analyses which examine DNAm marks individually. Results: We have developed a Bayesian model to infer which epialleles are present in multiple regions of the same tumour. We apply our method to reduced representation bisulfite sequencing (RRBS) data from multiple regions of one lung cancer tumour and a matched normal sample. The model borrows information from all tumour regions to leverage greater statistical power. The total number of epialleles, the epiallele DNAm patterns, and a noise hyperparameter are all automatically inferred from the data. Uncertainty as to which epiallele an observed sequencing read originated from is explicitly incorporated by marginalising over the appropriate posterior densities. The degree to which tumour samples are contaminated with normal tissue can be estimated and corrected for. By tracing the distribution of epialleles throughout the tumour we can infer the phylogenetic history of the tumour, identify epialleles that differ between normal and cancer tissue, and define a measure of global epigenetic disorder. Conclusions: Detection and comparison of epialleles within multiple tumour regions enables phylogenetic analyses, identification of differentially expressed epialleles, and provides a measure of epigenetic heterogeneity.","abstract":"Background: Epigenetic heterogeneity within a tumour can play an important role in tumour evolution and the emergence of resistance to treatment. It is increasingly recognised that the study of DNA methylation (DNAm) patterns along the genome - so-called `epialleles' - offers greater insight into epigenetic dynamics than conventional analyses which examine DNAm marks individually. Results: We have developed a Bayesian model to infer which epialleles are present in multiple regions of the same tumour. We apply our method to reduced representation bisulfite sequencing (RRBS) data from multiple regions of one lung cancer tumour and a matched normal sample. The model borrows information from all tumour regions to leverage greater statistical power. The total number of epialleles, the epiallele DNAm patterns, and a noise hyperparameter are all automatically inferred from the data. Uncertainty as to which epiallele an observed sequencing read originated from is explicitly incorporated by marginalising over the appropriate posterior densities. The degree to which tumour samples are contaminated with normal tissue can be estimated and corrected for. By tracing the distribution of epialleles throughout the tumour we can infer the phylogenetic history of the tumour, identify epialleles that differ between normal and cancer tissue, and define a measure of global epigenetic disorder. Conclusions: Detection and comparison of epialleles within multiple tumour regions enables phylogenetic analyses, identification of differentially expressed epialleles, and provides a measure of epigenetic heterogeneity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-25T14:24:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002485","title":"Coding and small non-coding transcriptional landscape of tuberous sclerosis complex cortical tubers: implications for pathophysiology and treatment","description":"Tuberous Sclerosis Complex (TSC) is a rare genetic disorder that results from a mutation in the TSC1 or TSC2 genes leading to constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1). TSC is associated with autism, intellectual disability and severe epilepsy. Cortical tubers are believed to represent the neuropathological substrates of these disabling manifestations in TSC. In the presented study we used high-throughput RNA sequencing in combination with systems-based computational approaches to investigate the complexity of the TSC molecular network. Overall we detected 438 differentially expressed genes and 991 differentially expressed small non-coding RNAs in cortical tubers compared to autopsy control brain tissue. We observed increased expression of genes associated with inflammatory, innate and adaptive immune responses. In contrast, we observed a down-regulation of genes associated with neurogenesis and glutamate receptor signaling. MicroRNAs represented the largest class of over-expressed small non-coding RNA species in tubers. In particular, our analysis revealed that the miR-34 family  (including miR-34a, miR-34b and miR-34c) was significantly over-expressed. Functional studies demonstrated the ability of miR-34b to modulate neurite outgrowth in mouse primary hippocampal neuronal cultures. This study provides new insights into the TSC transcriptomic network along with the identification of potential new treatment targets.","abstract":"Tuberous Sclerosis Complex (TSC) is a rare genetic disorder that results from a mutation in the TSC1 or TSC2 genes leading to constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1). TSC is associated with autism, intellectual disability and severe epilepsy. Cortical tubers are believed to represent the neuropathological substrates of these disabling manifestations in TSC. In the presented study we used high-throughput RNA sequencing in combination with systems-based computational approaches to investigate the complexity of the TSC molecular network. Overall we detected 438 differentially expressed genes and 991 differentially expressed small non-coding RNAs in cortical tubers compared to autopsy control brain tissue. We observed increased expression of genes associated with inflammatory, innate and adaptive immune responses. In contrast, we observed a down-regulation of genes associated with neurogenesis and glutamate receptor signaling. MicroRNAs represented the largest class of over-expressed small non-coding RNA species in tubers. In particular, our analysis revealed that the miR-34 family  (including miR-34a, miR-34b and miR-34c) was significantly over-expressed. Functional studies demonstrated the ability of miR-34b to modulate neurite outgrowth in mouse primary hippocampal neuronal cultures. This study provides new insights into the TSC transcriptomic network along with the identification of potential new treatment targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-26T09:37:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002486","title":"Kidney_tumour_DNA","description":"This is a bulk DNA and RNA sequencing study of human renal tumours","abstract":"This is supplementary bulk to single cell RNA sequencing that we are performing","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-26T13:16:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002487","title":"Kidney_tumour_RNA","description":"This is a bulk DNA and RNA sequencing study of human renal tumours","abstract":"This is supplementary bulk to single cell RNA sequencing that we are performing","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-26T13:22:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002488","title":"G_T_seq_on_single_human_neuronal_nuclei","description":"Single neuronal nuclei are isolated from deceased donors. G&amp;T-seq will be performed to obtain genome and transcriptome information from the same cell.","abstract":"DNA sequencing of single human neurons willl enable the comprehension of the developmental relations between these cells and reveal any active mutational processes. Moreover, the expression profiles will be used to associate these characteristics with functional cell states.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002489","title":"Paediatric IBD Mosaicism","description":"This is a DNA sequencing study investigating genetic mechanisms underpinning childhood inflammatory bowel disease.","abstract":"This is a DNA sequencing study investigating genetic mechanisms underpinning childhood inflammatory bowel disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-26T14:24:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002490","title":"Mutational signatures of aflatoxin","description":"Aflatoxin B1 (AFB1) is a mutagen and IARC (International Agency for Research on Cancer) Group 1 carcinogen that causes hepatocellular carcinoma (HCC). Here we present the first whole genome data on the mutational signatures of AFB1 exposure from a total of &gt; 40,000 mutations in four experimental systems: two different human cell lines, and in liver tumors in wild-type mice and in mice that carried a hepatitis B surface antigen transgene – this to model the multiplicative effects of aflatoxin exposure and hepatitis B in causing HCC. AFB1 mutational signatures from all four experimental systems were remarkably similar. We integrated the experimental mutational signatures with data from newly-sequenced HCCs from Qidong County, China, a region of well-studied aflatoxin exposure. This indicated that COSMIC mutational signature 24, previously hypothesized to stem from aflatoxin exposure, indeed likely represents AFB1 exposure, possibly combined with other exposures. Among published somatic mutation data, we found evidence of AFB1 exposure in 0.7% of HCCs treated in North America, 1% of HCCs from Japan, but 16% of HCCs from Hong Kong. Thus, aflatoxin exposure apparently remains a substantial public health issue in some areas. This aspect of our study exemplifies the promise of future widespread resequencing of tumor genomes in providing new insights into the contribution of mutagenic exposures to cancer incidence.","abstract":"Aflatoxin B1 (AFB1) is a mutagen and IARC (International Agency for Research on Cancer) Group 1 carcinogen that causes hepatocellular carcinoma (HCC). Here we present the first whole genome data on the mutational signatures of AFB1 exposure from a total of &gt; 40,000 mutations in four experimental systems: two different human cell lines, and in liver tumors in wild-type mice and in mice that carried a hepatitis B surface antigen transgene – this to model the multiplicative effects of aflatoxin exposure and hepatitis B in causing HCC. AFB1 mutational signatures from all four experimental systems were remarkably similar. We integrated the experimental mutational signatures with data from newly-sequenced HCCs from Qidong County, China, a region of well-studied aflatoxin exposure. This indicated that COSMIC mutational signature 24, previously hypothesized to stem from aflatoxin exposure, indeed likely represents AFB1 exposure, possibly combined with other exposures. Among published somatic mutation data, we found evidence of AFB1 exposure in 0.7% of HCCs treated in North America, 1% of HCCs from Japan, but 16% of HCCs from Hong Kong. Thus, aflatoxin exposure apparently remains a substantial public health issue in some areas. This aspect of our study exemplifies the promise of future widespread resequencing of tumor genomes in providing new insights into the contribution of mutagenic exposures to cancer incidence.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-29T09:51:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002491","title":"Mechanisms of primary drug resistance in FGFR1 amplified lung cancer","description":"The 8p12-p11 locus is frequently amplified in squamous cell lung cancer (SQLC); the receptor tyrosine kinase fibroblast growth factor receptor 1 (FGFR1) being one of the most prominent targets of this amplification. Thus, small molecules inhibiting FGFRs have been employed to treat FGFR1-amplified SQLC. However, only about 11% of such FGFR1-amplified tumors respond to single agent FGFR inhibition and several tumors exhibited insufficient tumor shrinkage, compatible with the existence of drug-resistant tumor cells.","abstract":"The 8p12-p11 locus is frequently amplified in squamous cell lung cancer (SQLC); the receptor tyrosine kinase fibroblast growth factor receptor 1 (FGFR1) being one of the most prominent targets of this amplification. Thus, small molecules inhibiting FGFRs have been employed to treat FGFR1-amplified SQLC. However, only about 11% of such FGFR1-amplified tumors respond to single agent FGFR inhibition and several tumors exhibited insufficient tumor shrinkage, compatible with the existence of drug-resistant tumor cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002492","title":"Genomic Profiling Reveals Spatial Intra-tumour Heterogeneity in Follicular Lymphoma","description":"Follicular lymphoma (FL) is an incurable indolent non-Hodgkin’s lymphoma (NHL) that behaves heterogeneously and is synonymous with the reciprocal translocation t(14;18)(q32;q21), leading to aberrant constitutive over-expression of BCL2 [ref]. High risk groups with poor overall survival include patients that transform to a high grade lymphoma, most commonly diffuse large B cell lymphoma (DLBCL) or progress early (within 2 years) of receiving treatment. Recently several studies have shed light on the diverse genomic landscape of FL, with frequently mutated genes including those involved in chromatin remodelling, (CREBBP, KMT2D, EZH2, EP300), immune modulation (TNFRSF14), JAK-STAT (STAT6, SOCS1), NF-ĸB (CARD11, MYD88, TNFAIP3) and mTORC1 signalling (RRAGC) [ref]. To date, the majority of these studies have either focussed on inter-patient genetic heterogeneity or established the extent of clonal heterogeneity as a patient’s tumour evolves over time. Furthermore, these temporal studies have alluded to the existence of a tumour-repopulating population (referred to as the common progenitor cell (CPC)) that evades treatment and acts as a reservoir, seeding each subsequent relapse and transformation event. Although these previous studies have illuminated the longitudinal clonal dynamics that occur in FL, our understanding of the degree of spatial or intra-tumour heterogeneity (ITH) that exists within an individual patient thus far remains limited. Earlier studies have predominantly focused on differences in cytological grade and immunophenotype between spatially separated lymph nodes and bone marrow, the most common site of extra-nodal involvement in FL, with genomic profiling restricted to examining somatic hypermutation patterns in IgVH genes [ref]. In contrast next generation sequencing has been increasingly utilised in solid organ malignancies to derive comprehensive genomic profiles from spatially separated sites. The seminal study by Gerlinger et al revealed profound differences in the genetic make-up between individual primary and metastatic sites of renal cell carcinoma [ref]. Significant heterogeneity has since been demonstrated both between and within lesions in the same patient in lung, pancreas and breast cancer with presumed driver mutations distributed within the “branches” of the evolutionary phylogenetic tree, suggesting that a single biopsy is incapable of capturing the full genomic heterogeneity of an individual’s malignancy [ref]. This geographical heterogeneity not only adds to the diverse pool of tumour subclones that may contribute to drug resistance mechanisms but importantly, presents a major obstacle for precision-based approaches focussed on targeting specific lesions within a single biopsy. In FL, the exponential increase in clinical trials using novel agents such as EZH2, PI3K and BTK inhibitors reflects this shift in cancer care and along with the development of molecular prognostic scores such as the m7-FLIPI highlights the clinical need to accurately define genomic alterations with clinical relevance. As the majority of FL patients manifest disseminated tumour involvement, we sought to uncover the extent and clinical importance of spatial heterogeneity in FL by comprehensively genetically profiling 22 synchronously removed spatially separated biopsies from 9 patients. Using a combination of whole exome and targeted deep sequencing, our results inferred the complex subclonal architecture within these tumours and the mutational differences between anatomical sites, demonstrating cases with significant intrinsic genetic diversity.","abstract":"Follicular lymphoma (FL) is an incurable indolent non-Hodgkin’s lymphoma (NHL) that behaves heterogeneously and is synonymous with the reciprocal translocation t(14;18)(q32;q21), leading to aberrant constitutive over-expression of BCL2 [ref]. High risk groups with poor overall survival include patients that transform to a high grade lymphoma, most commonly diffuse large B cell lymphoma (DLBCL) or progress early (within 2 years) of receiving treatment. Recently several studies have shed light on the diverse genomic landscape of FL, with frequently mutated genes including those involved in chromatin remodelling, (CREBBP, KMT2D, EZH2, EP300), immune modulation (TNFRSF14), JAK-STAT (STAT6, SOCS1), NF-ĸB (CARD11, MYD88, TNFAIP3) and mTORC1 signalling (RRAGC) [ref]. To date, the majority of these studies have either focussed on inter-patient genetic heterogeneity or established the extent of clonal heterogeneity as a patient’s tumour evolves over time. Furthermore, these temporal studies have alluded to the existence of a tumour-repopulating population (referred to as the common progenitor cell (CPC)) that evades treatment and acts as a reservoir, seeding each subsequent relapse and transformation event. Although these previous studies have illuminated the longitudinal clonal dynamics that occur in FL, our understanding of the degree of spatial or intra-tumour heterogeneity (ITH) that exists within an individual patient thus far remains limited. Earlier studies have predominantly focused on differences in cytological grade and immunophenotype between spatially separated lymph nodes and bone marrow, the most common site of extra-nodal involvement in FL, with genomic profiling restricted to examining somatic hypermutation patterns in IgVH genes [ref]. In contrast next generation sequencing has been increasingly utilised in solid organ malignancies to derive comprehensive genomic profiles from spatially separated sites. The seminal study by Gerlinger et al revealed profound differences in the genetic make-up between individual primary and metastatic sites of renal cell carcinoma [ref]. Significant heterogeneity has since been demonstrated both between and within lesions in the same patient in lung, pancreas and breast cancer with presumed driver mutations distributed within the “branches” of the evolutionary phylogenetic tree, suggesting that a single biopsy is incapable of capturing the full genomic heterogeneity of an individual’s malignancy [ref]. This geographical heterogeneity not only adds to the diverse pool of tumour subclones that may contribute to drug resistance mechanisms but importantly, presents a major obstacle for precision-based approaches focussed on targeting specific lesions within a single biopsy. In FL, the exponential increase in clinical trials using novel agents such as EZH2, PI3K and BTK inhibitors reflects this shift in cancer care and along with the development of molecular prognostic scores such as the m7-FLIPI highlights the clinical need to accurately define genomic alterations with clinical relevance. As the majority of FL patients manifest disseminated tumour involvement, we sought to uncover the extent and clinical importance of spatial heterogeneity in FL by comprehensively genetically profiling 22 synchronously removed spatially separated biopsies from 9 patients. Using a combination of whole exome and targeted deep sequencing, our results inferred the complex subclonal architecture within these tumours and the mutational differences between anatomical sites, demonstrating cases with significant intrinsic genetic diversity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-05-31T14:32:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002493","title":"Whole_Exome_PC9_and_A375","description":"Drug resistant population of PC9(human non-small cell lung cancer) or A375 (human melanoma) cell lines were used for this study. By exome sequencing, we will analyse mutations of cells in drug tolerent state and after drug holiday.","abstract":"Heterogeneity within cancer cell population in the response to drug treatment is generally observed. The relative contribution of mutational and nonmutation mechanisms to drug resistance and the role of tumor cell subpopulations remain unclear. By this exome sequencing study, we will analyse the mutation rate of cells in drug tolerent state and after drug holiday.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-01T09:28:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002494","title":"Profiling_molecular_heterogeneity_in_human_primary_microglia","description":"In the brain the cells that control inflammation are called a type of white blood cell called microglia. Microglia are located throughout the brain and spinal cord and account for 10–15% of all cells found within the brain. As the resident white blood cells, they are the main active immune defence in the central nervous system (CNS). Microglia are part of an important class of cells known as macrophages that have two main states: M1 and M2. M1 cells are pro- inflammatory, leading to more inflammation, while M2 are anti-inflammatory, and drive wound healing. In this study, we will collect primary microglia from surgical biospies of 100  individuals. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Microglia are the resident immune cells of the CNS, are located throughout the brain and spinal cord and account for 10–15% of all cells found within the brain. However, human microglia are a very challenging cell to study because they are hard to access. In this study we will collect a perform single cell sequencing on primary human microglia from 100 individuals.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-01T15:32:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002495","title":"Sampling of multi-centric lower grade glioma influences management and provides insight into gliomagenesis","description":"Rare multicentric lower-grade gliomas (LGG) represent a unique opportunity to study the heterogeneity between distinct tumor foci in a single patient, and to infer their origins and parallel patterns of evolution.  In this study, we integrate clinical features, histology and immunohistochemistry for 4 patients with multicentric LGG, arising both synchronously and metachronously. For 3 patients we analyze the phylogeny of the lesions using exome sequencing, including one case with a total of 8 samples from the two lesions. We show that each tumor in multicentric LGG cases may arise independently or may diverge very early in their development, presenting as genetically and histologically distinct tumors suggesting that comprehensive sampling of these lesions can significantly alter diagnosis and management.","abstract":"Rare multicentric lower-grade gliomas (LGG) represent a unique opportunity to study the heterogeneity between distinct tumor foci in a single patient, and to infer their origins and parallel patterns of evolution.  In this study, we integrate clinical features, histology and immunohistochemistry for 4 patients with multicentric LGG, arising both synchronously and metachronously. For 3 patients we analyze the phylogeny of the lesions using exome sequencing, including one case with a total of 8 samples from the two lesions. We show that each tumor in multicentric LGG cases may arise independently or may diverge very early in their development, presenting as genetically and histologically distinct tumors suggesting that comprehensive sampling of these lesions can significantly alter diagnosis and management.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-04T23:29:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002496","title":"H3K27ac ChIP-seq in TMPRSS2:ERG positive and negative prostate cancer tissue samples","description":"The TMPRSS2:ERG (T2E) structural rearrangements typifies  ~50% of prostate tumors and results in overexpression of the ERG transcription factor. Using chromatin data collected in T2E and non-T2E primary prostate tumors, we show a distinct cis-regulatory landscape between T2E and non-T2E, inclusive of Cluster Of Regulatory Elements (COREs). This is mediated by ERG co-option of HOXB13 and FOXA1 implementing a T2E-specific transcriptional profile. We also report a T2E-specific CORE on the structurally rearranged ERG locus arising from spreading of the TMPRSS2 locus pre-existing CORE, assisting in its overexpression. Finally, we show that the T2E-specific cis-regulatory landscape reveals a vulnerability against the NOTCH pathway. Taken together, our work shows that overexpressed ERG co-opts master transcription factors to deploy a unique cis-regulatory landscape inducing a druggable dependency on NOTCH signaling in T2E prostate tumors.","abstract":"The TMPRSS2:ERG (T2E) structural rearrangements typifies  ~50% of prostate tumors and results in overexpression of the ERG transcription factor. Using chromatin data collected in T2E and non-T2E primary prostate tumors, we show a distinct cis-regulatory landscape between T2E and non-T2E, inclusive of Cluster Of Regulatory Elements (COREs). This is mediated by ERG co-option of HOXB13 and FOXA1 implementing a T2E-specific transcriptional profile. We also report a T2E-specific CORE on the structurally rearranged ERG locus arising from spreading of the TMPRSS2 locus pre-existing CORE, assisting in its overexpression. Finally, we show that the T2E-specific cis-regulatory landscape reveals a vulnerability against the NOTCH pathway. Taken together, our work shows that overexpressed ERG co-opts master transcription factors to deploy a unique cis-regulatory landscape inducing a druggable dependency on NOTCH signaling in T2E prostate tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-05T22:44:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002497","title":"Combined use of whole-exome sequencing and subsequent targeted single-cell sequencing offers a tool for revealing subject-specific driver mutations and clonal evolution in cancer patients.","description":"Whole-exome sequencing of bulk bone marrow cells from 33 ET patients were conducted to identify possible driver mutations. Then targeted region sequencing of single HSCs from two representative patients was performed, one with JAK2 V617F and the other one with a CALR mutation.","abstract":"Whole-exome sequencing of bulk bone marrow cells from 33 ET patients were conducted to identify possible driver mutations. Then targeted region sequencing of single HSCs from two representative patients was performed, one with JAK2 V617F and the other one with a CALR mutation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002498","title":"Functional_genomics_of_the_Vaccines_Against_Salmonella_Typhi__VAST__Clinical_Trial","description":"As part of a Phase IIb, observer-blind, randomised controlled trial to assess the immunogenicity and protective efficacy of Vi conjugated (Vi-TCV) and unconjugated (Vi-PS) polysaccharide vaccines in preventing typhoid infection (in conjunction with typhoid challenge), RNA samples were collected for functional genomics (FG) post-vaccination and post challenge. Samples from individuals at pre-vaccination, and 1 and 7 days following vaccination with the Vi polysaccharide vaccine against typhoid or the Vi typhoid conjugate vaccine (TT conjugated) will be sequenced for detailed transcriptomics analysis. Following vaccination, participants were challenged with a dose of S. Typhi Quailes strain. To understand the immune response following challenge and how this is altered by vaccination, several time points following challenge will be sequenced.\n\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"As part of a Phase IIb, observer-blind, randomised controlled trial to assess the immunogenicity and protective efficacy of Vi conjugated (Vi-TCV) and unconjugated (Vi-PS) polysaccharide vaccines in preventing typhoid infection (in conjunction with typhoid challenge), we collected RNA samples for functional genomics (FG) post-vaccination and post challenge. In order to understand the functional genomic response to vaccination and relate this to outcome (Vi antibody titres, SBA etc.), we collected samples prior to vaccination, and day 1, and day 7 after vaccination. Transcriptional profiling of the response at these time points will give a large and unique dataset to define the host response to these two vaccines. Furthermore, we collected samples following challenge including time of bacteremia/onset of symptoms. Interrogating the transcriptional response at these time points will give detailed insight into alteration of the host response to infection.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002499","title":"Genetic Risk for Subsequent Neoplasms among Long-term Survivors of Childhood Cancer in the St. Jude Lifetime Cohort","description":"While childhood cancer survivors are known to be at increased risk of subsequent neoplasms (SNs), the contribution of germline mutations in cancer predisposition genes to the risk of SN is largely unknown. Whole-genome sequencing (30X) was performed on 3,006 5+ year survivors of childhood cancer (median age, 35.8 [range: 7.1-69.8] years) from the St. Jude Lifetime Cohort. Survivors underwent a comprehensive clinical assessment. Germline mutations in 156 cancer predisposition genes (SJCPG156), including a subset of 60 (SJCPG60) autosomal dominant genes with moderate to high penetrance, were classified for their pathogenicity. Piecewise exponential regression, stratified by radiation exposure, was used to evaluate the relative rate (RR) and 95% confidence interval (95% CI) of SN occurrence by mutation status. Pathogenic or likely pathogenic mutations in SJCPG156 and SJCPG60 were identified in 11.7% and 5.8% of survivors, respectively. The most frequently mutated SJCPG60 genes included RB1 (n=43), NF1 (n=22), BRCA2 (n=14), BRCA1 (n=12) and TP53 (n=10). Mutations in SJCPG60 were associated with the rate of subsequent sarcoma (RR, 10.3; 95% CI, 4.2 to 25.6) and breast cancer (RR, 13.3; 95% CI, 5.8 to 30.5) among irradiated survivors, and the rate of developing any SN (RR, 4.8; 95% CI, 2.4 to 9.4) and breast cancer (RR, 7.8; 95% CI, 2.5 to 24.0) among non-irradiated survivors. The rate of developing ≥2 histologically distinct SNs was increased 17.8-fold (95% CI, 3.5 to 89.8) among SJCPG60 mutation carriers treated without radiotherapy. Similar but attenuated associations were observed for mutations in SJCPG156.  Survivors who develop a SN without prior radiotherapy or who are diagnosed with a subsequent sarcoma or breast cancer within a site of prior radiotherapy should be referred to genetic counseling.","abstract":"While childhood cancer survivors are known to be at increased risk of subsequent neoplasms (SNs), the contribution of germline mutations in cancer predisposition genes to the risk of SN is largely unknown. Whole-genome sequencing (30X) was performed on 3,006 5+ year survivors of childhood cancer (median age, 35.8 [range: 7.1-69.8] years) from the St. Jude Lifetime Cohort. Survivors underwent a comprehensive clinical assessment. Germline mutations in 156 cancer predisposition genes (SJCPG156), including a subset of 60 (SJCPG60) autosomal dominant genes with moderate to high penetrance, were classified for their pathogenicity. Piecewise exponential regression, stratified by radiation exposure, was used to evaluate the relative rate (RR) and 95% confidence interval (95% CI) of SN occurrence by mutation status. Pathogenic or likely pathogenic mutations in SJCPG156 and SJCPG60 were identified in 11.7% and 5.8% of survivors, respectively. The most frequently mutated SJCPG60 genes included RB1 (n=43), NF1 (n=22), BRCA2 (n=14), BRCA1 (n=12) and TP53 (n=10). Mutations in SJCPG60 were associated with the rate of subsequent sarcoma (RR, 10.3; 95% CI, 4.2 to 25.6) and breast cancer (RR, 13.3; 95% CI, 5.8 to 30.5) among irradiated survivors, and the rate of developing any SN (RR, 4.8; 95% CI, 2.4 to 9.4) and breast cancer (RR, 7.8; 95% CI, 2.5 to 24.0) among non-irradiated survivors. The rate of developing ≥2 histologically distinct SNs was increased 17.8-fold (95% CI, 3.5 to 89.8) among SJCPG60 mutation carriers treated without radiotherapy. Similar but attenuated associations were observed for mutations in SJCPG156.  Survivors who develop a SN without prior radiotherapy or who are diagnosed with a subsequent sarcoma or breast cancer within a site of prior radiotherapy should be referred to genetic counseling.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-06T19:17:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002500","title":"CRISPR_Cas9_Cancer_Cell_Line_Screen_RNAseq","description":"Whole genome CRISPR drop out screen in cancer cell lines - RNASeq","abstract":"Cancer cell lines from the GDSC1000 panel have been transduced with Cas9 to produce a stably expressing Cas9 version of the cancer cell lines.  This study will compare expression profiles of the parental and Cas9 versions of each cell line using RNASeq.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002501","title":"Genome-wide expression profiles to compare array-based, RNAseq and NanoString technologies in patients with resected pancreatic ductal carcinoma.","description":"Using formalin-fixed paraffin embedded (FFPE) tissues collected prospectively in patients with resected pancreatic ductal carcinoma (PDC) we generated genome-wide expression profiles to compare array-based, RNAseq and NanoString technologies. Samples included in the study were collected 17 patients. After careful selection by the pathologist of 17 malignant cells-enriched, 7 stroma-enriched, and 6 normal (normal pancreas in 4 cases and normal duodenum in 2 cases) regions, sections were macrodissected, and total RNA extracted. Two additional FFPE-frozen matched-paired PDAC from our local Biobank were included. Our study represents the most extensive work comparing three technologies to generate gene expression profiles from FFPE samples, and provides technical guidance for future biomarker studies in samples collected prospectively in the context of clinical trials.","abstract":"Using formalin-fixed paraffin embedded (FFPE) tissues collected prospectively in patients with resected pancreatic ductal carcinoma (PDC) we generated genome-wide expression profiles to compare array-based, RNAseq and NanoString technologies. Samples included in the study were collected 17 patients. After careful selection by the pathologist of 17 malignant cells-enriched, 7 stroma-enriched, and 6 normal (normal pancreas in 4 cases and normal duodenum in 2 cases) regions, sections were macrodissected, and total RNA extracted. Two additional FFPE-frozen matched-paired PDAC from our local Biobank were included. Our study represents the most extensive work comparing three technologies to generate gene expression profiles from FFPE samples, and provides technical guidance for future biomarker studies in samples collected prospectively in the context of clinical trials.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-09T09:08:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002502","title":"PGE2_and_advanced_liver_disease_patient","description":"Transcriptome of innate immune cells isolated from patient with advanced liver disease\n\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared","abstract":"Transcriptome of innate immune cells isolated from patient with advanced liver disease\n\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002503","title":"Genome_wide_association_scan_of_aseptic_loosening_after_total_hip_arthroplasty","description":"This is a genome-wide association scan of aseptic loosening after total hip replacement in a UK European population.","abstract":"12% of total hip arthroplasty prostheses (THA) fail within 10 years, and require revision surgery. Aseptic loosening, the risk of which varies between individuals, accounts for 62% of these failures. This is a genome-wide association scan of aseptic loosening after total hip replacement in a UK European population Here we aim to identify key genetic risk factors and pathways contributing to aseptic loosening.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002504","title":"Transcriptome sequencing of intravenous leiomyomatosis and  uterine myoma","description":"Up to now, there are two hypothesis about the pathogenesis of the  relationship of intravenous leiomyomatosis and  uterine myoma. One theory suggests that the IVL comes from the smooth muscle cell in the vessel wall.The other theory indicates that the IVL derives from the uterine myometrium. However, limited to the technology, few studies have been deeply explore the underlying relation. In this study, we employ the RNA sequencing to explore the molecule relationship between IVL and uterus myoma. In order to identify the molecule relationship between IVl and  uterine myoma we conducted transcriptome sequencing and bioinformaitc analysis","abstract":"Up to now, there are two hypothesis about the pathogenesis of the  relationship of intravenous leiomyomatosis and  uterine myoma. One theory suggests that the IVL comes from the smooth muscle cell in the vessel wall.The other theory indicates that the IVL derives from the uterine myometrium. However, limited to the technology, few studies have been deeply explore the underlying relation. In this study, we employ the RNA sequencing to explore the molecule relationship between IVL and uterus myoma. In order to identify the molecule relationship between IVl and  uterine myoma we conducted transcriptome sequencing and bioinformaitc analysis","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-09T18:42:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002505","title":"H3K27ac and RNA-seq data of neuroblastoma PDXs and/or primary tumors","description":"This study includes H3K27ac ChIP-seq and RNA-seq data of 6 neuroblastoma PDXs. It also contains RNA-seq data of 3 pairs of neuroblastoma tumors obtained at diagnosis and relapse. The MAP-GR-B25-NB-1 PDX was derived from the relapse of pair 1.","abstract":"This study includes H3K27ac ChIP-seq and RNA-seq data of 6 neuroblastoma PDXs. It also contains RNA-seq data of 3 pairs of neuroblastoma tumors obtained at diagnosis and relapse. The MAP-GR-B25-NB-1 PDX was derived from the relapse of pair 1.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-12T14:44:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002506","title":"Targeted next-generation sequencing detects novel gene-phenotype associations and expands the mutational spectrum in cardiomyopathie","description":"Cardiomyopathies are a heterogeneous group of primary diseases of the myocardium,including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), andarrhythmogenic right ventricular cardiomyopathy (ARVC), with higher morbidity andmortality. These diseases are genetically diverse and associated with rare mutations ina large number of genes, many of which overlap among the phenotypes. To betterinvestigate the genetic overlap between these three phenotypes and to identify newgenotype-phenotype correlations, we designed a custom gene panel consisting of 115genes known to be associated with cardiomyopathic phenotypes and channelopathies.A cohort of 38 unrelated patients, 16 affected by DCM, 14 by HCM and 8 by ARVC,was recruited for the study on the basis of more severe phenotypes and family historyof cardiomyopathy and/or sudden death.","abstract":"Cardiomyopathies are a heterogeneous group of primary diseases of the myocardium,including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), andarrhythmogenic right ventricular cardiomyopathy (ARVC), with higher morbidity andmortality. These diseases are genetically diverse and associated with rare mutations ina large number of genes, many of which overlap among the phenotypes. To betterinvestigate the genetic overlap between these three phenotypes and to identify newgenotype-phenotype correlations, we designed a custom gene panel consisting of 115genes known to be associated with cardiomyopathic phenotypes and channelopathies.A cohort of 38 unrelated patients, 16 affected by DCM, 14 by HCM and 8 by ARVC,was recruited for the study on the basis of more severe phenotypes and family historyof cardiomyopathy and/or sudden death.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-12T17:33:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002507","title":"ATRX mutant neuroblastoma is sensitive to EZH2 inhibition via modulation of neuronal differentiation.","description":"Mutations and structural alterations of the SWI/SNF-like chromatin remodeler ATRX have been reported at high frequency in a number of adult and pediatric tumors1. However, the consequences of ATRX (Alpha Thalassemia/Mental Retardation, X-linked) mutations in cancer and their underlying epigenetic sensitivities remain ill defined. Particularly intriguing are the large N-terminal deletions of ATRX in neuroblastoma that generate in-frame fusion (IFF) proteins1–3 devoid of key chromatin interaction domains. Here we demonstrate that neuroblastoma cells harbouring ATRX IFFs have distinct gene expression programs compared to neuroblastoma cells that are wild type for ATRX. This is due in part to H3K27me3-mediated silencing of REST (RE1 Silencing Transcription Factor) target genes involved in neuronal differentiation. In turn, we find that ATRX IFF cells display exquisite sensitivity to EZH2 inhibition in both adherent and tumorsphere conditions, due in part to derepression of neurogenesis genes, including REST targets. Examination of the epigenomic landscape of a pediatric neuroblastoma tumor harboring an ATRX IFF revealed that H3K27me3 occupies a subset of REST target genes that are transcriptionally silenced, and are sensitive to EZH2 inhibition in our cell-based assays. Thus, our study greatly advances our understanding of indolent neuroblastoma and identifies EZH2 inhibition as a potential therapy for patients with ATRX mutant disease. Further, these studies may be applicable to other ATRX mutant pediatric malignancies, particularly those carrying similar structural alterations of ATRX.","abstract":"Mutations and structural alterations of the SWI/SNF-like chromatin remodeler ATRX have been reported at high frequency in a number of adult and pediatric tumors1. However, the consequences of ATRX (Alpha Thalassemia/Mental Retardation, X-linked) mutations in cancer and their underlying epigenetic sensitivities remain ill defined. Particularly intriguing are the large N-terminal deletions of ATRX in neuroblastoma that generate in-frame fusion (IFF) proteins1–3 devoid of key chromatin interaction domains. Here we demonstrate that neuroblastoma cells harbouring ATRX IFFs have distinct gene expression programs compared to neuroblastoma cells that are wild type for ATRX. This is due in part to H3K27me3-mediated silencing of REST (RE1 Silencing Transcription Factor) target genes involved in neuronal differentiation. In turn, we find that ATRX IFF cells display exquisite sensitivity to EZH2 inhibition in both adherent and tumorsphere conditions, due in part to derepression of neurogenesis genes, including REST targets. Examination of the epigenomic landscape of a pediatric neuroblastoma tumor harboring an ATRX IFF revealed that H3K27me3 occupies a subset of REST target genes that are transcriptionally silenced, and are sensitive to EZH2 inhibition in our cell-based assays. Thus, our study greatly advances our understanding of indolent neuroblastoma and identifies EZH2 inhibition as a potential therapy for patients with ATRX mutant disease. Further, these studies may be applicable to other ATRX mutant pediatric malignancies, particularly those carrying similar structural alterations of ATRX.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-12T20:28:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002508","title":"Fibroblast heterogeneity and immunosuppressive environment in Human breast cancer","description":"Carcinoma-associated fibroblasts (CAF) are key players in the tumor microenvironment. Here, by combining 6 well-known stromal markers, we identify four CAF subsets (CAF-S1 to CAF-S4) in human breast cancer (BC) that exhibit distinct activation patterns and accumulate differently in BC subtypes.","abstract":"Carcinoma-associated fibroblasts (CAF) are key players in the tumor microenvironment. Here, by combining 6 well-known stromal markers, we identify four CAF subsets (CAF-S1 to CAF-S4) in human breast cancer (BC) that exhibit distinct activation patterns and accumulate differently in BC subtypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-13T11:32:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002509","title":"Combination Therapies for Personalised Cancer Medicine in drug resistant EGFR mutant lung cancer","description":"This study involves mutagenizing a range of different cell lines with ENU to identify those mutations which engender resistance to targeted treatment.\nIn the last decade we have begun to move towards the use of targeted therapeutics in the clinic, often resulting in dramatic response rates in cancer patients. However, clinical experience has demonstrated time and time again that such responses are invariably followed by the development of drug resistance. Identification of the underlying mechanisms may enable us to reverse such resistance. Traditional methods of modelling this resistance in vitro can lead to a plethora of potential resistance mechanisms that can be difficult to decipher.","abstract":"This study involves mutagenizing a range of different cell lines with ENU to identify those mutations which engender resistance to targeted treatment.\nIn the last decade we have begun to move towards the use of targeted therapeutics in the clinic, often resulting in dramatic response rates in cancer patients. However, clinical experience has demonstrated time and time again that such responses are invariably followed by the development of drug resistance. Identification of the underlying mechanisms may enable us to reverse such resistance. Traditional methods of modelling this resistance in vitro can lead to a plethora of potential resistance mechanisms that can be difficult to decipher.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-14T09:51:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002510","title":"High_depth_sequencing_of_human_skin_SCCs","description":"We wish to sequence human skin tumour at high depth using our custom bait set to assess the degree of polycolanality in these tumours.","abstract":"We wish to sequence human skin tumour at high depth using our custom bait set to assess the degree of polycolanality in these tumours.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002511","title":"Genomic and epigenomic characterization of juvenile myelomonocytic leukemia (JMML)","description":"Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood. While some cases show spontaneous remission, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment option for the majority of patients, however, the 5-year event-free survival reaches only about 50%. Hyperactive RAS signaling is assumed to be the main driving event in JMML. It is caused by genetic alterations in CBL, KRAS, NF1, NRAS, or PTPN11 in about 90% of patients. So far, there is no clear understanding of how RAS pathway mutations relate to the heterogeneous disease biology and variable clinical outcome seen in JMML patients. As a consequence, established clinical and genetic markers fail to fully represent the observed disease heterogeneity. We hypothesized that DNA methylation profiling, either alone or in combination with genetic alterations, might provide a molecular basis for disease classification. Genome wide DNA methylation analysis using the HumanMethylation450 Bead Chip array was performed in a discovery cohort of 20 patients (19 JMML, 1 Noonan syndrome). The clinical relevance of our findings was assessed in an unselected sample set consisting of 147 consecutive patients with JMML (n=129) or Noonan syndrome (n=18) associated myeloproliferative disorder (n=18) registered in the EWOG-MDS 1998 &amp; 2006 trials. Data integration was performed in a subset of patients with available exome sequencing (n=50) and expression profiling (n=15) data. This integrated approach identified three JMML subgroups characterized by distinct clinical and biological features. This analysis further suggested a molecular mechanism by which additional genetic events, presumably further activating the RAS-RAF-MEK-ERK pathway, mediate DNA hypermethylation via up-regulation of DNMTs in more aggressive JMML cases.","abstract":"Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood. While some cases show spontaneous remission, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment option for the majority of patients, however, the 5-year event-free survival reaches only about 50%. Hyperactive RAS signaling is assumed to be the main driving event in JMML. It is caused by genetic alterations in CBL, KRAS, NF1, NRAS, or PTPN11 in about 90% of patients. So far, there is no clear understanding of how RAS pathway mutations relate to the heterogeneous disease biology and variable clinical outcome seen in JMML patients. As a consequence, established clinical and genetic markers fail to fully represent the observed disease heterogeneity. We hypothesized that DNA methylation profiling, either alone or in combination with genetic alterations, might provide a molecular basis for disease classification. Genome wide DNA methylation analysis using the HumanMethylation450 Bead Chip array was performed in a discovery cohort of 20 patients (19 JMML, 1 Noonan syndrome). The clinical relevance of our findings was assessed in an unselected sample set consisting of 147 consecutive patients with JMML (n=129) or Noonan syndrome (n=18) associated myeloproliferative disorder (n=18) registered in the EWOG-MDS 1998 &amp; 2006 trials. Data integration was performed in a subset of patients with available exome sequencing (n=50) and expression profiling (n=15) data. This integrated approach identified three JMML subgroups characterized by distinct clinical and biological features. This analysis further suggested a molecular mechanism by which additional genetic events, presumably further activating the RAS-RAF-MEK-ERK pathway, mediate DNA hypermethylation via up-regulation of DNMTs in more aggressive JMML cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-14T11:52:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002512","title":"Mutation_burden_in_sun_exposed_eyelid__MSSE_","description":"Eyelid skin from blepharoplasty surgery will be collected from patients of different ethnic origin (Chinese, Malay, Indian and Caucasion) exposed to tropical sunshine. 2mm2 biopsies will be collected and DNA sequenced using a specific bait capture set and at high depth. The aim is to try and see if different mutations expand in different ethnic populations.","abstract":"Eyelid skin from blepharoplasty surgery will be collected from patients of different ethnic origin (Chinese, Malay, Indian and Caucasion) exposed to tropical sunshine. 2mm2 biopsies will be collected and DNA sequenced using a specific bait capture set and at high depth. The aim is to try and see if different mutations expand in different ethnic populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-15T11:17:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002513","title":"Pants_RNA_sequencing","description":"Sequence a total of 800 blood serum RNA samples collected from 200 “rapid responders” and 200 “non-responders” before (wk 0) and after (wk14) their first dose of anti-TNF therapy. We will perform a series of differential gene expression analyses to identify genes where expression differs between the rapid responders and non-responders. All these individuals have been included in our recent 15X whole-genome sequencing study so we will also search for genetic variants that influence expression responses to anti-TNF therapy. We will combine our genetic and genomic data with clinical and questionnaire data to build predictive models of anti-TNF response. We also sequence 150 samples from ~50 individuals with serum available at day 0, day 2 and wk 14. We will use these data to investigate the early transcriptional responses to anti-TNF therapy and see if these correlate with those seen at wk14. We know that immunogenicity likely plays a role in primary non-response and loss of response, and we will use these datat see if we can detect early transcriptional signatures associated with these negative treatment outcomes.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"RNA-seq data from 800 serum samples ascertained by the Personalised anti-TNF therapy in Crohn’s disease study (PANTS, https://www.pantsdb.co.uk/#/home). 400 serum samples were ascertained at wk 0, prior to the first ever dose of anti-TNF therapy. A further serum sample was collected from the same 400 individuals fourteen weeks after the initial dose. 200 of the individuals are defined as rapid-responders to Anti-TNF and 200 are defined as rapid nonresponders. The 400 individuals in this study are drawn from a larger cohort of ~1700 individuals currently in PANTS. These data have been generated to investigate the biological mechanisms that underlie anti-TNF primary nonresponse and to aid the development of personalised anti-TNF treatment strategies, through the identification of clinically meaningful serological and genetic/genomic predictive markers","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002514","title":"TGF-β signaling suppresses tumor surveillance by inducing the differentiation of tumor associated NK cells into type 1 innate lymphoid cells","description":"Avoiding destruction by immune cells is a hallmark of cancer, yet how tumors ultimately evade natural killer (NK) cell control remains incompletely defined. In this study we describe the conversion of NK cells (CD49a-CD49b+Eomes+) into intermediate type 1 innate lymphoid (intILC1) cell (CD49a+CD49b+Eomes+) and ILC1 (CD49a+CD49b-Eomes-) cell populations in the tumor microenvironment dependent on TGF-β signaling. Strikingly, intILC1s/ILC1s were unable to control local tumor growth and metastasis, whereas NK cells favored tumor immune surveillance. Experiments using TNF-blocking antibodies suggested that innate immune escape was partially mediated by TNF-producing ILC1s. Together our data highlight the unexpected plasticity of group 1 ILCs in tumors and reveal a novel mechanism by which tumors escape innate immune surveillance.","abstract":"Avoiding destruction by immune cells is a hallmark of cancer, yet how tumors ultimately evade natural killer (NK) cell control remains incompletely defined. In this study we describe the conversion of NK cells (CD49a-CD49b+Eomes+) into intermediate type 1 innate lymphoid (intILC1) cell (CD49a+CD49b+Eomes+) and ILC1 (CD49a+CD49b-Eomes-) cell populations in the tumor microenvironment dependent on TGF-β signaling. Strikingly, intILC1s/ILC1s were unable to control local tumor growth and metastasis, whereas NK cells favored tumor immune surveillance. Experiments using TNF-blocking antibodies suggested that innate immune escape was partially mediated by TNF-producing ILC1s. Together our data highlight the unexpected plasticity of group 1 ILCs in tumors and reveal a novel mechanism by which tumors escape innate immune surveillance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001002515","title":"Pharmacogenomic landscape of patient-derived cells informs precision oncology therapy","description":"Outcomes of anticancer therapy vary dramatically among patients, which may be caused by the specific molecular alterations in each patient’s tumor. Precision oncology aims to apply optimal therapies for each tumor based on its molecular characteristics. We have established a resource reporting the genomic and transcriptomic profiles of 462 patient tumor-derived cells (PDCs) across 14 cancer types, together with responses to 60 targeted agents. Compared with long-term cultured cancer cell lines, PDCs better recapitulate the molecular profiles of the original tumors. Among other unreported associations, we identify molecular factors inducing resistance to EGFR inhibitors in glioblastoma, and we suggest repurposing ibrutinib (currently used in hematological malignancies) for EGFR-specific therapy in gliomas. Lastly, using a retrospective clinical study, we find that PDC-derived sensitivities can be used to predict patient responses.","abstract":"Outcomes of anticancer therapy vary dramatically among patients, which may be caused by the specific molecular alterations in each patient’s tumor. Precision oncology aims to apply optimal therapies for each tumor based on its molecular characteristics. We have established a resource reporting the genomic and transcriptomic profiles of 462 patient tumor-derived cells (PDCs) across 14 cancer types, together with responses to 60 targeted agents. Compared with long-term cultured cancer cell lines, PDCs better recapitulate the molecular profiles of the original tumors. Among other unreported associations, we identify molecular factors inducing resistance to EGFR inhibitors in glioblastoma, and we suggest repurposing ibrutinib (currently used in hematological malignancies) for EGFR-specific therapy in gliomas. Lastly, using a retrospective clinical study, we find that PDC-derived sensitivities can be used to predict patient responses.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-16T09:16:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002516","title":"PDL1_CRISPR_Screen","description":"Regulators of PDL1 expression will be studied by a pooled CRISPR screening approach in human melanoma cell line C092, which express high levels of PDL1 in WT condition. Kosuke Yusa's library human v1.1 will be used to look at genes responsible for downregulation of PDL1, which will be of potential therapeutic interest. Cells will be sorted by FACS 2 weeks after infection, and guides in the PDL1 low/dim population will be compared to unsorted fraction.","abstract":"egulators of PDL1 expression will be studied by a pooled CRISPR screening approach in human melanoma cell line C092, which express high levels of PDL1 in WT condition. Kosuke Yusa's library human v1.1 will be used to look at genes responsible for downregulation of PDL1, which will be of potential therapeutic interest.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002517","title":"Distinct genomic profile and specific targeted drug responses in adult cerebellar glioblastoma","description":"Only a few studies have reported the molecular characteristics of adult cerebellar glioblastoma (C-GBM), a subtype comprising 1% of glioblastoma cases located within the infratentorial brain region due to the rarity. By identifying genomic profiles from 19 adult C-GBM samples, we revealed the genetic intertumoral heterogeneity in C-GBM as well as distinct genomic characteristics from those of supratentorial glioblastomas (S-GBMs), emphasizing the need of individualized therapies for C-GBM patients.","abstract":"Only a few studies have reported the molecular characteristics of adult cerebellar glioblastoma (C-GBM), a subtype comprising 1% of glioblastoma cases located within the infratentorial brain region due to the rarity. By identifying genomic profiles from 19 adult C-GBM samples, we revealed the genetic intertumoral heterogeneity in C-GBM as well as distinct genomic characteristics from those of supratentorial glioblastomas (S-GBMs), emphasizing the need of individualized therapies for C-GBM patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-19T04:15:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002518","title":"Linking the epigenetic landscape in chronic lymphocytic leukemia to deregulated chromatin networks","description":"Aberrant chromatin features and epigenetic signaling emerge as an important part of the tumor disease state in chronic lymphocytic leukemia (CLL). However, an integrative analysis of the malignant chromatin landscape is currently missing. Here, we mapped DNA-methylation, nucleosome position, 7 histone modifications, ATAC-seq and the transcriptome in primary CD19+ sorted B-cells from the peripheral blood of CLL patients in comparison to non-malignant lymphocytes of healthy donor reference samples. On the &gt; 50 kb scale we identified global differences with respect to DNA methylation, nucleosome positioning and histone modifications in CLL. Furthermore, a chromatin state annotation was developed to identify deregulated chromatin features of promoters and enhancers in CLL. By integrating these findings with an ATAC-seq based transcription factor binding analysis we identified a set of promoters and enhancers specific to CLL that were enriched in certain transcription factors binding motifs and genes of the BCR signaling pathway. Thus, our study provides an in-depth map of the CLL chromatin landscape and links chromatin state changes at promoters and enhancers to deregulated pathways.","abstract":"Aberrant chromatin features and epigenetic signaling emerge as an important part of the tumor disease state in chronic lymphocytic leukemia (CLL). However, an integrative analysis of the malignant chromatin landscape is currently missing. Here, we mapped DNA-methylation, nucleosome position, 7 histone modifications, ATAC-seq and the transcriptome in primary CD19+ sorted B-cells from the peripheral blood of CLL patients in comparison to non-malignant lymphocytes of healthy donor reference samples. On the &gt; 50 kb scale we identified global differences with respect to DNA methylation, nucleosome positioning and histone modifications in CLL. Furthermore, a chromatin state annotation was developed to identify deregulated chromatin features of promoters and enhancers in CLL. By integrating these findings with an ATAC-seq based transcription factor binding analysis we identified a set of promoters and enhancers specific to CLL that were enriched in certain transcription factors binding motifs and genes of the BCR signaling pathway. Thus, our study provides an in-depth map of the CLL chromatin landscape and links chromatin state changes at promoters and enhancers to deregulated pathways.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-20T08:38:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002519","title":"OA_Functional_Genomics_Pilot","description":"OA affects &gt;40% of individuals over 70y and is a leading cause of pain and loss of physical function in the UK, affecting 8.5 million patients. The molecular changes leading to the pathogenesis of OA are still poorly understood.  We will obtain diseased and non-diseased tissue (cartilage) following total knee replacement surgery, coupled with a blood sample.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"OA affects &gt;40% of individuals over 70y and is a leading cause of pain and loss of physical function in the UK, affecting 8.5 million patients. The molecular changes leading to the pathogenesis of OA are still poorly understood.  We will obtain diseased and non-diseased tissue (cartilage) following total knee replacement surgery, coupled with a blood sample.\nThis pilot follows on from successful work with UK-based orthopaedic surgeon collaborators and focuses on a new collection from Greece. We will use the same protocols as in the UK and assess the quality of the DNA and RNA that is extracted to see if this is a feasible collaboration for a wider project.\nWe will generate genotype data and will characterise the pairs of diseased and non-diseased tissue samples in terms of transcription (RNASeq). We will apply integrative approaches to combine information across the –omics levels to characterise genes, pathways, and networks that underlie osteoarthritis progression","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002520","title":"Local In Time Statistics for processual research","description":"Background: Functional genomics in a processual analysis cover the time-dependent changes in transcriptomics and epigenetics before diagnosis of a disease, reflecting the changes in both life style and disease processes. The aim of this paper is to explore the dynamic, time-dependent mechanisms of the metastatic processes, using blood transcriptomics and including time in a continuous manner. For achieving this goal we develop new statistical methods based on statistics that are local in time.  Methods: The new statistical method, Local In Time Statistics (LITS), is based on calculating statistics in moving windows and randomization. The method has been tested for the analysis of a dataset that collectively provides information on the blood transcriptome up to eight years before breast cancer diagnosis. The dataset from the NOWAC Post-genome Cohort consists of 467 case-control pairs matched on birth year and time of blood sampling. The data for a pair is the difference in log2 gene expression between the case and control. The stratified analyses are based on important biological differences like metastatic versus non-metastatic cancer, and the mode of cancer detection, i.e. screening detected versus clinically detected cancers. The dataset was used for examining whether the gene expression profile varies between cases and controls, with time, or between cases with and without metastases. Results: The null hypotheses of no differences between cases and controls, no time-dependent changes, and no differences between different strata were all rejected. For screening detected cancers the probability of correct prediction of metastasis status was best in year 1 before diagnosis compared to year 3 and 4 before diagnosis for clinically detected cancers. The predictor was not very sensitive to the number of genes included.Conclusions: Using a new statistical method, LITS, we have demonstrated time-dependent changes of the blood transcriptome up to eight years before breast cancer diagnosis.","abstract":"Background: Functional genomics in a processual analysis cover the time-dependent changes in transcriptomics and epigenetics before diagnosis of a disease, reflecting the changes in both life style and disease processes. The aim of this paper is to explore the dynamic, time-dependent mechanisms of the metastatic processes, using blood transcriptomics and including time in a continuous manner. For achieving this goal we develop new statistical methods based on statistics that are local in time.  Methods: The new statistical method, Local In Time Statistics (LITS), is based on calculating statistics in moving windows and randomization. The method has been tested for the analysis of a dataset that collectively provides information on the blood transcriptome up to eight years before breast cancer diagnosis. The dataset from the NOWAC Post-genome Cohort consists of 467 case-control pairs matched on birth year and time of blood sampling. The data for a pair is the difference in log2 gene expression between the case and control. The stratified analyses are based on important biological differences like metastatic versus non-metastatic cancer, and the mode of cancer detection, i.e. screening detected versus clinically detected cancers. The dataset was used for examining whether the gene expression profile varies between cases and controls, with time, or between cases with and without metastases. Results: The null hypotheses of no differences between cases and controls, no time-dependent changes, and no differences between different strata were all rejected. For screening detected cancers the probability of correct prediction of metastasis status was best in year 1 before diagnosis compared to year 3 and 4 before diagnosis for clinically detected cancers. The predictor was not very sensitive to the number of genes included.Conclusions: Using a new statistical method, LITS, we have demonstrated time-dependent changes of the blood transcriptome up to eight years before breast cancer diagnosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-21T09:17:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002521","title":"Cylindromas_sun_protected_and_exposed","description":"The project aims to look at mutational signatures in a rare inherited skin tumour syndrome called CYLD cutaneous syndrome. These patients develop multiple skin tumours that are seen at sun exposed and sun protected sites. We plan to carry out WGS on carefully curated tumours from such patients. We then plan to analyse this data for mutational signatures, comparing this between sun exposed and sun protected sites.","abstract":"The project aims to look at mutational signatures in a rare inherited skin tumour syndrome called CYLD cutaneous syndrome. These patients develop multiple skin tumours that are seen at sun exposed and sun protected sites. We plan to carry out WGS on carefully curated tumours from such patients. We then plan to analyse this data for mutational signatures, comparing this between sun exposed and sun protected sites.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-21T09:43:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002522","title":"Exome_sequencing_of_Non_syndromic_Congenital_Heart_Defects","description":"Exome sequencing of ~1,800 patients with non-syndromic Congenical Heart Defects (CHD) to identify genes enriched for damaging rare variants that increase risk of CHD","abstract":"Exome sequencing of ~1,800 patients with non-syndromic Congenical Heart Defects (CHD) to identify genes enriched for damaging rare variants that increase risk of CHD","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-21T10:51:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002523","title":"Genome_Diversity_in_Africa_Project__Uganda","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region.\nThe Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).\nOur scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics","abstract":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region.\nThe Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).\nOur scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-21T10:51:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002524","title":"Drug___Genome_wide_CRISPR_Cas9_Drop_out_of_Human_Cancer_Cell_Lines","description":"This study will combine drug treatment with genome-wide loss-of-function CRISPR-Cas9 drop out screens in a search for novel drug combination strategies.\n\n*Sequencing is performed on PCR products from the amplification of gRNA segments introduced into commercial cell lines. Cellular DNA or RNA are not sequenced. This data is defined as \"Other Biological/Biochemical Assay Data\" under the WTSI datasharing guidelines and consequently will be released at the time of publication and/or through faculty websites.","abstract":"he goal of this study is to identify potential novel drug combinations by simulataneous treating a cancer cell line with a sub lethal dose of the drug of interest with a whole-genome CRISPR drop-out screen.  This approach aims to find genes whose depletion sensitises cells to the drug.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002525","title":"G_T_seq_on_single_human_neuronal_nuclei___Transcriptomes","description":"Single neuronal nuclei are isolated from deceased donors. G&amp;T-seq will be performed to obtain genome and transcriptome information from the same cell.","abstract":"DNA sequencing of single human neurons willl enable the comprehension of the developmental relations between these cells and reveal any active mutational processes. Moreover, the expression profiles will be used to associate these characteristics with functional cell states.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002526","title":"The aim of this study was to identify underlying hub genes and dysregulated pathways associated with the development of HCC using bioinformatics analysis.","description":"In the present study, we identified differentially expressed protein-coding genes from RNA transcriptional profiling performed on 11 paired cancer tissues and adjacent non-cancerous tissues. Then, we conducted GO, KEGG, PPI network and centralities analyses to study and identify changes in pathways and hub genes. The aim of this study was to improve understanding of HCC carcinogenesis by providing information concerning the genetic changes that occur during disease progression and to uncover the expression of biomarkers with potential use for clinical diagnosis, treatment, and monitoring of disease progression.","abstract":"In the present study, we identified differentially expressed protein-coding genes from RNA transcriptional profiling performed on 11 paired cancer tissues and adjacent non-cancerous tissues. Then, we conducted GO, KEGG, PPI network and centralities analyses to study and identify changes in pathways and hub genes. The aim of this study was to improve understanding of HCC carcinogenesis by providing information concerning the genetic changes that occur during disease progression and to uncover the expression of biomarkers with potential use for clinical diagnosis, treatment, and monitoring of disease progression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-21T15:12:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002527","title":"Establishing multiple omics baselines for three Southeast Asian populations in the Singapore Integrative Omics Study","description":"In this study, we established population reference measurements across multiple omic technologies and investigated the inter-population variations in each omic and phenotypic measurements in three major populations in Singapore. The measurements include genome-wide SNPs, gene probesets expression, lipid species and circulating miRNAs.","abstract":"In this study, we established population reference measurements across multiple omic technologies and investigated the inter-population variations in each omic and phenotypic measurements in three major populations in Singapore. The measurements include genome-wide SNPs, gene probesets expression, lipid species and circulating miRNAs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-21T16:31:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002528","title":"Orthotopic Patient-Derived Xenografts of Pediatric Solid Tumors","description":"Pediatric solid tumors arise from endodermal, ectodermal, or mesodermal lineages. Although the overall survival of children with solid tumors is 75%-80%, that of children with recurrent disease is below 30%. To capture the complexity and diversity of pediatric solid tumors and establish new models of recurrent disease, we developed a protocol to produce orthotopic patient-derived xenografts (O-PDXs) at diagnosis, recurrence, and autopsy. Tumor specimens were received from 168 patients, and 64 O-PDXs were established for 12 types of pediatric solid tumors. The origins of the O-PDX tumors were reflected in their gene-expression profiles and epigenomes.  Genomic profiling of the tumors, including detailed clonal analysis, was performed to determine whether the clonal population in the xenograft recapitulated the patient’s tumor. We identified several drug vulnerabilities and showed that the combination of a WEE1 inhibitor (AZD1775), irinotecan, and vincristine can lead to complete response in multiple rhabdomyosarcoma O-PDX tumors in vivo.","abstract":"Pediatric solid tumors arise from endodermal, ectodermal, or mesodermal lineages. Although the overall survival of children with solid tumors is 75%-80%, that of children with recurrent disease is below 30%. To capture the complexity and diversity of pediatric solid tumors and establish new models of recurrent disease, we developed a protocol to produce orthotopic patient-derived xenografts (O-PDXs) at diagnosis, recurrence, and autopsy. Tumor specimens were received from 168 patients, and 64 O-PDXs were established for 12 types of pediatric solid tumors. The origins of the O-PDX tumors were reflected in their gene-expression profiles and epigenomes.  Genomic profiling of the tumors, including detailed clonal analysis, was performed to determine whether the clonal population in the xenograft recapitulated the patient’s tumor. We identified several drug vulnerabilities and showed that the combination of a WEE1 inhibitor (AZD1775), irinotecan, and vincristine can lead to complete response in multiple rhabdomyosarcoma O-PDX tumors in vivo.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-21T16:53:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002529","title":"Transcriptomics_of_Leishmania_infected_iPS_derived_macrophages","description":"We would like to develop the iPS cells as a model system to understand host-parasite interactions of Leishmania. As\na small initial step, we would like to exploit some existing material to use RNA-seq to determine how Leishmania\ninfected iPSC-derived macrophages differ in transcription from uninfected cells and iPSC-derived macrophages\nactivated by other pathogens. In addition, we will determine how transcription in Leishmania that have infected iPSCderived macrophages differ from Leishmania in other macrophage populations: these steps are more-or-less\nvalidating this as a model host cell.\n\n This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"RNA-seq transcriptomics of iPSC-derived macrophages infected with Leishmania major, seeking to investigate the\nhost cell response to Leishmania infection in this system.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002530","title":"Adult_skin","description":"We are doing single-cell RNAseq from adult skin to study new cell populations and their functions.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"This project aims to deconstruct the human skin to its individual cellular constituents using single cell technologies. In this pursuit, we will define the cell census and functional niches within the human skin","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002531","title":"Germline polymorphisms direct the somatic architecture of prostate cancer","description":"NOT USED (moved to EGAS00001000900 )Germline polymorphisms are well-known to modulate cancer risk. Surprisingly, though, the influence of the germline on the molecular features that emerge in a tumour (germline-somatic interactions) is relatively understudied. Germline polymorphisms in BRCA2 are known to change the somatic aberration profile of tumours, but there has been no systematic study on interactions between the germline genome and somatic mutations. To fill this gap in knowledge, we quantified the influence of germline genetics on the somatic evolution of prostate cancer. We first demonstrate that two thirds of known risk SNPs influence somatic mutational profiles. We then discover 92 novel SNPs that exhibit germline-somatic mutational interactions, and validate a subset of these in an independent cohort. Using machine-learning approaches, we show that somatic aberrations in a prostate tumour can be predicted prior to diagnosis based on a man’s germline genetics – information present at birth. Taken together, these studies suggest germline factors play a large role in driving tumour evolution.","abstract":"NOT USED (moved to EGAS00001000900 )Germline polymorphisms are well-known to modulate cancer risk. Surprisingly, though, the influence of the germline on the molecular features that emerge in a tumour (germline-somatic interactions) is relatively understudied. Germline polymorphisms in BRCA2 are known to change the somatic aberration profile of tumours, but there has been no systematic study on interactions between the germline genome and somatic mutations. To fill this gap in knowledge, we quantified the influence of germline genetics on the somatic evolution of prostate cancer. We first demonstrate that two thirds of known risk SNPs influence somatic mutational profiles. We then discover 92 novel SNPs that exhibit germline-somatic mutational interactions, and validate a subset of these in an independent cohort. Using machine-learning approaches, we show that somatic aberrations in a prostate tumour can be predicted prior to diagnosis based on a man’s germline genetics – information present at birth. Taken together, these studies suggest germline factors play a large role in driving tumour evolution.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002532","title":"Cell_cycle_dependent_mechanisms_controlling_differentiation_of_haematopoietic_stem_cells","description":"Single cell RNA-seq on the 10x Chromium technology to characterize cell fate decisions in human IPSC lines\n\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Our group has recently shown that the cell-cycle directs cell fate decisions in human pluripotent stem cells (hPSCs) by controlling signalling pathways orchestrating cell fate choice trough Cyclin D-CDK4/6 complexes. Interestingly, genetic studies in the mouse have shown that absence of Cyclin Ds, CDKs or other regulators of the cell-cycle induces haematopoietic defects in vivo, suggesting that similar mechanisms could be important for blood cells production. Therefore we propose with this project to define the role of cell-cycle regulators in haematopoiesis by using hPSCs as an in vitro model to study early specification and differentiation of haematopoietic progenitors (HPCs).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002533","title":"Genome-wide genetic and epigenetic dataset of pancreatic acinar cell carcinomas","description":"Pancreatic acinar cell carcinoma (ACC) is an aggressive exocrine tumor with largely unknown biology. To identify potential targets for personalized treatment, integrative genome- and epigenome-wide analyses were performed. The results show frequently aberrant DNA methylation, abundant chromosomal amplifications and deletions, and mutational signatures suggesting defective DNA repair. In contrast to pancreatic ductal adenocarcinoma, no recurrent point mutations are known. The tumor suppressors ID3, ARID1A, APC, and CDKN2A are frequently impaired also on the protein level and thus potentially affect ACC tumorigenesis. Consequently, this work identifies potential novel therapeutic targets in ACC for drugs recently approved for precision cancer therapy.","abstract":"Pancreatic acinar cell carcinoma (ACC) is an aggressive exocrine tumor with largely unknown biology. To identify potential targets for personalized treatment, integrative genome- and epigenome-wide analyses were performed. The results show frequently aberrant DNA methylation, abundant chromosomal amplifications and deletions, and mutational signatures suggesting defective DNA repair. In contrast to pancreatic ductal adenocarcinoma, no recurrent point mutations are known. The tumor suppressors ID3, ARID1A, APC, and CDKN2A are frequently impaired also on the protein level and thus potentially affect ACC tumorigenesis. Consequently, this work identifies potential novel therapeutic targets in ACC for drugs recently approved for precision cancer therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-23T13:17:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002534","title":"Orphan_Tumour_Study___RNAseq","description":"The aim of this study is to study the genomes of ultra rare childhood tumours","abstract":"The aim of this study is to study the genomes of ultra rare childhood tumours","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-23T15:04:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002535","title":"Genome-wide Ancestry and Demographic History of African-Descendant Maroon Communities from French Guiana and Surname.","description":"The transatlantic slave trade (TAST) was the largest forced migration in world history. However, the origins of the enslaved Africans and their admixture dynamics remain unclear. To investigate the demographic history of African-descendant Marron populations, we generated genome-wide SNP data (4.3 million markers) from 107 individuals from three African-descendant populations in South America, as well as 124 individuals from six west African populations to complement underrepresented African data sets.  Our study sheds additional light on the demographic consequences of the TAST and illustrates how genetic data can complement historical sources.","abstract":"The transatlantic slave trade (TAST) was the largest forced migration in world history. However, the origins of the enslaved Africans and their admixture dynamics remain unclear. To investigate the demographic history of African-descendant Marron populations, we generated genome-wide SNP data (4.3 million markers) from 107 individuals from three African-descendant populations in South America, as well as 124 individuals from six west African populations to complement underrepresented African data sets.  Our study sheds additional light on the demographic consequences of the TAST and illustrates how genetic data can complement historical sources.","study_type":"Other","pubmed_ids":[29100086],"external_links":null,"is_released":true,"released_date":"2017-06-26T10:52:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002536","title":"A biobank of patient-derived pediatric brain tumor models","description":"Brain tumors are the leading cause of cancer-related death in children. Genomic studies have provided insights into molecular\nsubgroups and oncogenic drivers of pediatric brain tumors that may lead to novel therapeutic strategies. To evaluate new\ntreatments, better preclinical models adequately reflecting the biological heterogeneity are needed. Through the Children’s Oncology Group ACNS02B3 study, we have generated and comprehensively characterized 30 patient-derived orthotopic\nxenograft models and 7 cell lines representing 14 molecular subgroups of pediatric brain tumors. Patient-derived orthotopic\nxenograft models were found to be representative of the human tumors they were derived from in terms of histology, immunohistochemistry, gene expression, DNA methylation, copy number, and mutational profiles. In vivo drug sensitivity of targeted therapeutics was associated with distinct molecular tumor subgroups and specific genetic alterations. These models and their molecular characterization provide an unprecedented resource for the cancer community to study key oncogenic drivers and to evaluate novel treatment strategies.","abstract":"Brain tumors are the leading cause of cancer-related death in children. Genomic studies have provided insights into molecular\nsubgroups and oncogenic drivers of pediatric brain tumors that may lead to novel therapeutic strategies. To evaluate new\ntreatments, better preclinical models adequately reflecting the biological heterogeneity are needed. Through the Children’s Oncology Group ACNS02B3 study, we have generated and comprehensively characterized 30 patient-derived orthotopic\nxenograft models and 7 cell lines representing 14 molecular subgroups of pediatric brain tumors. Patient-derived orthotopic\nxenograft models were found to be representative of the human tumors they were derived from in terms of histology, immunohistochemistry, gene expression, DNA methylation, copy number, and mutational profiles. In vivo drug sensitivity of targeted therapeutics was associated with distinct molecular tumor subgroups and specific genetic alterations. These models and their molecular characterization provide an unprecedented resource for the cancer community to study key oncogenic drivers and to evaluate novel treatment strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-27T13:10:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002537","title":"Integrative genomic analysis identifies multiple subtypes and therapeutic targets in acute erythroid leukemia","description":"Acute erythroid leukemia (AEL) is a high risk leukemia of poorly understood genetic basis, and controversy regarding diagnosis in the spectrum of myelodysplasia and myeloid leukemia. We compared genomic and clinical features of 159 childhood and adult AEL cases to non-AEL myeloid disorders, and identified patterns of mutation that describe 5 age-related subgroups with distinct transcriptional profiles: adult, TP53-mutated; NPM1-mutated; KMT2A-mutated/rearranged; adult, DDX41-mutated; and pediatric, NUP98-rearranged.  Mutational spectra were age-dependent and significantly associated with outcome, with NPM1 mutations and high HOXB9 expression being associated with favorable prognosis, and TP53, FLT3 and RB1 alterations associated with poor survival. Targetable signaling mutations were present in 45% of cases, and include recurrent mutations of ALK and NTRK1, the latter of which drive erythroid leukemogenesis sensitive to TRK inhibition. This genomic landscape of AEL provides the framework for accurate diagnosis and risk stratification of this disease, and the rationale for testing targeted therapies in this form of leukemia that has hitherto and dismal outcome.","abstract":"Acute erythroid leukemia (AEL) is a high risk leukemia of poorly understood genetic basis, and controversy regarding diagnosis in the spectrum of myelodysplasia and myeloid leukemia. We compared genomic and clinical features of 159 childhood and adult AEL cases to non-AEL myeloid disorders, and identified patterns of mutation that describe 5 age-related subgroups with distinct transcriptional profiles: adult, TP53-mutated; NPM1-mutated; KMT2A-mutated/rearranged; adult, DDX41-mutated; and pediatric, NUP98-rearranged.  Mutational spectra were age-dependent and significantly associated with outcome, with NPM1 mutations and high HOXB9 expression being associated with favorable prognosis, and TP53, FLT3 and RB1 alterations associated with poor survival. Targetable signaling mutations were present in 45% of cases, and include recurrent mutations of ALK and NTRK1, the latter of which drive erythroid leukemogenesis sensitive to TRK inhibition. This genomic landscape of AEL provides the framework for accurate diagnosis and risk stratification of this disease, and the rationale for testing targeted therapies in this form of leukemia that has hitherto and dismal outcome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-27T15:22:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002538","title":"The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space","description":"Glioblastoma is characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the role of the epigenome in glioblastoma disease progression. Here, we present genome-scale maps of DNA methylation in matched primary and recurring glioblastoma tumors, using data from a highly annotated clinical cohort that was selected through a national patient registry. We demonstrate the feasibility of DNA methylation mapping in a large set of routinely collected FFPE samples, and we validate bisulfite sequencing as a multipurpose assay that allowed us to infer a range of different genetic, epigenetic, and transcriptional characteristics of the profiled tumor samples. On the basis of these data, we identified subtle differences between primary and recurring tumors, links between DNA methylation and the tumor microenvironment, and an association of epigenetic tumor heterogeneity with patient survival. In summary, this study establishes an open resource for dissecting DNA methylation heterogeneity in a genetically diverse and heterogeneous cancer, and it demonstrates the feasibility of integrating epigenomics, radiology, and digital pathology for a national cohort, thereby leveraging existing samples and data collected as part of routine clinical practice.","abstract":"Glioblastoma is characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the role of the epigenome in glioblastoma disease progression. Here, we present genome-scale maps of DNA methylation in matched primary and recurring glioblastoma tumors, using data from a highly annotated clinical cohort that was selected through a national patient registry. We demonstrate the feasibility of DNA methylation mapping in a large set of routinely collected FFPE samples, and we validate bisulfite sequencing as a multipurpose assay that allowed us to infer a range of different genetic, epigenetic, and transcriptional characteristics of the profiled tumor samples. On the basis of these data, we identified subtle differences between primary and recurring tumors, links between DNA methylation and the tumor microenvironment, and an association of epigenetic tumor heterogeneity with patient survival. In summary, this study establishes an open resource for dissecting DNA methylation heterogeneity in a genetically diverse and heterogeneous cancer, and it demonstrates the feasibility of integrating epigenomics, radiology, and digital pathology for a national cohort, thereby leveraging existing samples and data collected as part of routine clinical practice.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-27T15:36:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002539","title":"Multi-region sequencing of metastatic colorectal cancer","description":"In order to reconstruct the evolutionary history of metastatic colorectal cancer, we performed whole-exome sequencing of 10 metastatic colorectal cancer patients for whom the primary tumor and matched distant metastases to the brain (n=10), liver (n=1), lung (n=1), as well as lymph node metastases (n=4) were available. For 6 of the 10 patients, multiple regions (n=2-5) of the primary tumor and distant metastases were sequenced.","abstract":"In order to reconstruct the evolutionary history of metastatic colorectal cancer, we performed whole-exome sequencing of 10 metastatic colorectal cancer patients for whom the primary tumor and matched distant metastases to the brain (n=10), liver (n=1), lung (n=1), as well as lymph node metastases (n=4) were available. For 6 of the 10 patients, multiple regions (n=2-5) of the primary tumor and distant metastases were sequenced.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002540","title":"In-depth characterization of the mutational signature of cisplatin in a human cell line and in tumors","description":"Cisplatin based chemotherapeutic regimens are the standard of care for many tumor types. As cisplatin reacts with DNA, it likely leaves a characteristic pattern of somatic mutations, called a mutational signature. Mutational signatures can provide insight into tumorigenesis and serve as biomarkers for mutagenic processes and exposures. Therefore we set out to generate the mutational signature of cisplatin in MCF10A, a normal human mammary epithelial cell line. We extensively characterized the mutations induced by cisplatin treatment and identified strongly preferred tri- and pentanucleotide contexts. Analysis of transcription strand bias was consistent with cisplatin adducts on both guanines and adenines. Numbers of small insertions and deletions were low, but the proportion of dinucleotide substitutions (DNSs) was high: &gt; 7% of single nucleotide substitutions were part of DNSs, likely related to the inter- and intra-strand crosslinks formed by cisplatin. Several bases were markedly enriched at sites flanking DNSs, and there was no observable transcriptional strand bias for DNSs. We identified evidence of cisplatin exposure in 6 out of 342 hepatocellular carcinoma genomes based on the single nucleotide and DNSs patterns. We also identified the single and dinucleotide signatures of cisplatin in 3 esophageal adenocarcinomas with known cisplatin exposure. We conclude that incorporating information such as dinucleotide spectra into mutational signature analysis is crucial for correct assignment of mutational signatures to tumors. Furthermore, we emphasize the need for standardization of protocols for studying mutagenic processes, in particular the in vitro models used.","abstract":"Cisplatin based chemotherapeutic regimens are the standard of care for many tumor types. As cisplatin reacts with DNA, it likely leaves a characteristic pattern of somatic mutations, called a mutational signature. Mutational signatures can provide insight into tumorigenesis and serve as biomarkers for mutagenic processes and exposures. Therefore we set out to generate the mutational signature of cisplatin in MCF10A, a normal human mammary epithelial cell line. We extensively characterized the mutations induced by cisplatin treatment and identified strongly preferred tri- and pentanucleotide contexts. Analysis of transcription strand bias was consistent with cisplatin adducts on both guanines and adenines. Numbers of small insertions and deletions were low, but the proportion of dinucleotide substitutions (DNSs) was high: &gt; 7% of single nucleotide substitutions were part of DNSs, likely related to the inter- and intra-strand crosslinks formed by cisplatin. Several bases were markedly enriched at sites flanking DNSs, and there was no observable transcriptional strand bias for DNSs. We identified evidence of cisplatin exposure in 6 out of 342 hepatocellular carcinoma genomes based on the single nucleotide and DNSs patterns. We also identified the single and dinucleotide signatures of cisplatin in 3 esophageal adenocarcinomas with known cisplatin exposure. We conclude that incorporating information such as dinucleotide spectra into mutational signature analysis is crucial for correct assignment of mutational signatures to tumors. Furthermore, we emphasize the need for standardization of protocols for studying mutagenic processes, in particular the in vitro models used.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002541","title":"Flexible_multiplex_PCR_for_genotyping_by_sequencing","description":"This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"To provide a cost-efficient and flexible pipeline for multiplex PCR-based genotyping projects internal to the institute","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002542","title":"Ancient_DNA_from_Pakistan","description":"Ancient DNA has revolutionized our understanding of population movements and replacements, particularly in Europe. Till now very few ancient DNA samples have been analysed from South Asia, home to the Indus Valley civilizations that trace their root to the Neolithic period. Climactic conditions are generally not suitable for DNA preservation in this region. Nevertheless, some studies have been successfully carried out on mitochondrial DNA and DNA extracted from remains in the Himalayas. Here, we will analyse three ancient samples from North-western Pakistan. The study will aid in understanding whether there was extensive population movement, replacement or admixture in this region and shed light on inhabitants that lived there during the Neolithic period (3000-4000 years ago) before Alexander's invasion in 323 B.C.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Ancient DNA has revolutionized our understanding of population movements and replacements, particularly in Europe. Till now very few ancient DNA samples have been analysed from South Asia, home to the Indus Valley civilizations that trace their root to the Neolithic period. Climactic conditions are generally not suitable for DNA preservation in this region. Nevertheless, some studies have been successfully carried out on mitochondrial DNA and DNA extracted from remains in the Himalayas. Here, we will analyse three ancient samples from North-western Pakistan. The study will aid in understanding whether there was extensive population movement, replacement or admixture in this region and shed light on inhabitants that lived there during the Neolithic period (3000-4000 years ago) before Alexander's invasion in 323 B.C.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002543","title":"PanCuRx Translational Research Initiative","description":"The goal of the PanCuRx TRI is to seek solutions to the high fatality rate of pancreatic adenocarcinoma (PDAC), the most common type of pancreatic cancer, by generating new knowledge about the genetics and biology of the disease, mechanisms of how tumours grow and tailored treatment options.\n\n PDAC is the fourth leading cause of cancer death in Canada and is expected to become the second-leading cause of cancer death within the next decade. The current five-year survival rate of eight per cent is the lowest of all epithelial cancers. There are major clinical challenges to treating the disease, including the fact that PDAC spreads to other parts of the body early so surgical removal of the tumour benefits few patients, that PDAC has proven relatively resistant to systemic therapies such as chemotherapy and that there has been limited benefit from the use of newer molecular targeted agents. \n\nThe PanCuRx team has created the world’s first resource of tumour-purified PDAC whole genomes; more than 500 PDAC samples, with combined clinical annotation, have been successfully sequenced and analyzed at the Ontario Institute for Cancer research in Toronto. The resulting clinical genomic resource created from this data has led to multiple new findings that have established a framework to better understand PDAC biology and lays the foundation for new genomic approaches to better understanding the disease. The team also launched a clinical trial called COMPASS (Comprehensive Molecular Characterization of Advanced Ductal Pancreas Adenocarcinoma for Better Treatment Selection: A Prospective Study), which is recruiting patients with advanced PDAC (both locally advanced and metastatic) at The Princess Margaret Cancer Centre (PM) in Toronto. The study uses the molecular results from individual patient tumours to guide selection of better second line treatment on a case-by-case basis. The primary objective of the initial study was to assess the feasibility of collecting tumour materials from patients with advanced PDAC and delivering results within 56 days of biopsy. Having achieved this objective, the trial has expanded to other cancer centres across Canada.\n \nPancreatic cancer is one of the most deadly forms of cancer and outcomes have not improved in four decades. The PanCuRx initiative is providing a better understanding of the disease and actively applying new knowledge to cancer patients through clinical trials. This knowledge will help to improve quality of life and prolong survival for pancreatic cancer patients worldwide.","abstract":"The goal of the PanCuRx TRI is to seek solutions to the high fatality rate of pancreatic adenocarcinoma (PDAC), the most common type of pancreatic cancer, by generating new knowledge about the genetics and biology of the disease, mechanisms of how tumours grow and tailored treatment options.\n\n PDAC is the fourth leading cause of cancer death in Canada and is expected to become the second-leading cause of cancer death within the next decade. The current five-year survival rate of eight per cent is the lowest of all epithelial cancers. There are major clinical challenges to treating the disease, including the fact that PDAC spreads to other parts of the body early so surgical removal of the tumour benefits few patients, that PDAC has proven relatively resistant to systemic therapies such as chemotherapy and that there has been limited benefit from the use of newer molecular targeted agents. \n\nThe PanCuRx team has created the world’s first resource of tumour-purified PDAC whole genomes; more than 500 PDAC samples, with combined clinical annotation, have been successfully sequenced and analyzed at the Ontario Institute for Cancer research in Toronto. The resulting clinical genomic resource created from this data has led to multiple new findings that have established a framework to better understand PDAC biology and lays the foundation for new genomic approaches to better understanding the disease. The team also launched a clinical trial called COMPASS (Comprehensive Molecular Characterization of Advanced Ductal Pancreas Adenocarcinoma for Better Treatment Selection: A Prospective Study), which is recruiting patients with advanced PDAC (both locally advanced and metastatic) at The Princess Margaret Cancer Centre (PM) in Toronto. The study uses the molecular results from individual patient tumours to guide selection of better second line treatment on a case-by-case basis. The primary objective of the initial study was to assess the feasibility of collecting tumour materials from patients with advanced PDAC and delivering results within 56 days of biopsy. Having achieved this objective, the trial has expanded to other cancer centres across Canada.\n \nPancreatic cancer is one of the most deadly forms of cancer and outcomes have not improved in four decades. The PanCuRx initiative is providing a better understanding of the disease and actively applying new knowledge to cancer patients through clinical trials. This knowledge will help to improve quality of life and prolong survival for pancreatic cancer patients worldwide.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-06-28T20:13:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002544","title":"A_study_utilising_tissue_from_deceased_organ_donors_to_investigate_regenerative_cellular_therapies_and_related_physiological_and_developmental_processes_","description":"Single cell RNA-seq characterisation of  the hepatobiliary system cell lineages/populations \n\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"The heaptobilliary system is involved in a broad number of metabolic function including digestion, detoxification and protein secretion. The goal of this project is to define precisely the cellular and functional diversity of the organs composing the hepatobiliary system including the biliary three and the liver. In addition, we aim to study the consequence of liver disease such as NAFLD/NASH on this cellular composition. Ultimately, this study will identify new cell types for therapeutic development.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002545","title":"Xten_analysis_placental_biopsies","description":"Xten analysis placental biopsies","abstract":"Xten analysis placental biopsies","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002546","title":"Functional_classification_of_variants_associated_with_blood_traits_by_MPRA","description":"We will use massively parallel reporter assays to probe regulatory function of common and rare genetic variants. We will identify carriers of candidate variants and proxies in high linkage disequilibrium from individuals collected as part of Blueprint Human Variation project. DNA fragments will be enriched by PCR and then cloned into a sequencing based reporter assay such as that implemented in Vockley et al. 2015, which will be subsequently transfected into relevant blood cell model systems (HL60, U937, K562, etc). We will extract RNA, background control DNA and carry out standard total RNA-seq, extract barcode or allele specific enhancer sequences to quantify the different transcripts. We will construct a scoring system with aim to classify different genetic haplotypes and regulatory contexts driven by different regulatory factors.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"From Astle et al 2016 we have identified 278 low and rare frequency variants predicted to influence blood cell traits through a regulatory change, as assessed through overlap with annotations such as open chromatin or transcription factor binding. We will use massively parallel reporter assays to probe regulatory function and experimentally fine map SNPs as in Vockley et al 2015. Using DNA from individuals collected as Blueprint Human Variation project we will create pools of PCR amplicons encapsulating predicted causal lead SNP, other proxy SNPs and potentially contributing regulatory features. This pool of DNA fragments containing common and rare haplotypes will then be cloned into MPRA vector, Arnold et al 2014. The resultant vector will be subsequently transfected into relevant blood cell model systems (HL60, U937, K562, etc). We will isolate RNA &amp; DNA and carry out standard total RNA-seq, control DNA and extract barcode or allele specific enhancer sequences to quantify the different alleles. We will construct a scoring system with aim to classify different genetic haplotypes and regulatory contexts driven by different regulatory factors.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002547","title":"Clonal evolution study of Intrahepatic cholangiocarcinoma in Zhongshan Hospital","description":"Clonal evolution study of Intrahepatic cholangiocarcinoma","abstract":"Clonal evolution study of Intrahepatic cholangiocarcinoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002548","title":"WGS__15x__of_139_Maasai_individuals_from_the_HapMap_collection","description":"We have recently sequenced the whole RNA of 600 African 1000G and HapMap samples to be used in our African Transcriptome Project. The aim of the project was to generate high coverage RNAseq data (Illumina HiSeq) from 6 different populations across Africa; the first large-scale resource to examine eQTLs within Africa. The necessary complement to such resource is whole genome sequence data from the same samples. To date such data are publicly available for all but one population, the HapMap Maasai. We propose here to generate whole genome sequences for the Maasai population.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"We have sequenced to medium depth (15x) 139 HapMap Maasai samples for which no WGS data were available previously.\nWe have carried this sequencing as part of our African Transcriptome Project. The aim of the project was to generate high coverage RNAseq data (Illumina HiSeq) from 6 different populations across Africa; the first large-scale resource to examine eQTLs within Africa. The necessary complement to such resource is whole genome sequence data from the same samples.Maasai population.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002549","title":"Genomic landscape of human diversity across Madagascar","description":"Although situated ~400 km from the east coast of Africa, Madagascar exhibits cultural, linguistic, and genetic traits from both Southeast Asia and Eastern Africa. The settlement history remains contentious; we therefore used a grid-based approach to sample at high-resolution the genomic diversity (including maternal lineages, paternal lineages, and genome-wide data) across 257 villages and 2704 Malagasy individuals. We find a common Bantu and Austronesian descent for all Malagasy individuals with a limited paternal contribution from Europe and the Middle East. Admixture and demographic growth happened recently, suggesting a rapid settlement of Madagascar during the last millennium. However, the distribution of African and Asian ancestry across the island reveals that the admixture was sex biased and happened heterogeneously across Madagascar, suggesting independent colonization of Madagascar from Africa and Asia rather than settlement by an already-admixed population. In addition, there are geographic influences on the present genomic diversity, independent of the admixture, showing that a few centuries is sufficient to produce detectable genetic structure in human populations.","abstract":"Although situated ~400 km from the east coast of Africa, Madagascar exhibits cultural, linguistic, and genetic traits from both Southeast Asia and Eastern Africa. The settlement history remains contentious; we therefore used a grid-based approach to sample at high-resolution the genomic diversity (including maternal lineages, paternal lineages, and genome-wide data) across 257 villages and 2704 Malagasy individuals. We find a common Bantu and Austronesian descent for all Malagasy individuals with a limited paternal contribution from Europe and the Middle East. Admixture and demographic growth happened recently, suggesting a rapid settlement of Madagascar during the last millennium. However, the distribution of African and Asian ancestry across the island reveals that the admixture was sex biased and happened heterogeneously across Madagascar, suggesting independent colonization of Madagascar from Africa and Asia rather than settlement by an already-admixed population. In addition, there are geographic influences on the present genomic diversity, independent of the admixture, showing that a few centuries is sufficient to produce detectable genetic structure in human populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-04T13:53:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002550","title":"High frequency of RUNX1 mutation in myelodysplastic syndrome patients with whole-arm translocation of der(1;7)(q10;p10).","description":"The der(1;7)(q10;p10) is a recurrent chromosomal abnormality in MDS, resulting in trisomy 1q and monosomy 7q. There is some controversy over the prognosis of the der(1;7)(q10;p10). The genetic basis of MDS patients with der(1;7)(q10;p10) remains poorly defined. In this study, we have documented the disease features and the mutational landscape of a series of patients with der(1;7)(q10;p10). We observed that MDS patients with der(1;7)(q10;p10) present male predominance and have a better outcome than the -7/del(7q) group. Our findings revealed that the mutatome of patients with der(1;7)(q10;p10) is different from that of MDS with -7/del(7q). We demonstrate for the first time, to our knowledge, that der(1;7)(q10;p10) is associated with a high frequency of mutations in RUNX1 (40.9%). We found that most the mutations were located in the Runt domain. These results indicated that RUNX1 mutations might participate in the pathogenesis of MDS patients with der(1;7)(q10;p10).","abstract":"The der(1;7)(q10;p10) is a recurrent chromosomal abnormality in MDS, resulting in trisomy 1q and monosomy 7q. There is some controversy over the prognosis of the der(1;7)(q10;p10). The genetic basis of MDS patients with der(1;7)(q10;p10) remains poorly defined. In this study, we have documented the disease features and the mutational landscape of a series of patients with der(1;7)(q10;p10). We observed that MDS patients with der(1;7)(q10;p10) present male predominance and have a better outcome than the -7/del(7q) group. Our findings revealed that the mutatome of patients with der(1;7)(q10;p10) is different from that of MDS with -7/del(7q). We demonstrate for the first time, to our knowledge, that der(1;7)(q10;p10) is associated with a high frequency of mutations in RUNX1 (40.9%). We found that most the mutations were located in the Runt domain. These results indicated that RUNX1 mutations might participate in the pathogenesis of MDS patients with der(1;7)(q10;p10).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002551","title":"Y_chromosome_mis_segregation_in_the_DLD_1_cell_line","description":"Study of the well-established DLD-1 colorectal cancer cell line, engineered with an inactivatable Y centromere that leads to mis-segregation. The goal is to gain insights into the mechanism of chromothripsis due to chromosome mis-segration.","abstract":"Study of the well-established DLD-1 colorectal cancer cell line, engineered with an inactivatable Y centromere that leads to mis-segregation. The goal is to gain insights into the mechanism of chromothripsis due to chromosome mis-segration.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-06T08:34:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002552","title":"Single_cell_RNA_sequencing_of_menstrual_fluid","description":"Menstrual fluid (MF) is an accessible source of large numbers of live cells of high biomedical interest. During menstruation, the female body sheds 35–80ml of MF containing blood and cells (in single cells or in clumps) from the uterine lining, the cervix, the ovaries and the vaginal lining. This rich source of live cells has been previously proposed as a scalable source of live uterine NK cells and mesenchymal stem cells for research and therapy. Despite its potential, knowledge of the cellular composition and relative representation of the multiple reproductive tissues in menstrual fluid is limited. In this study we assay the cell type composition of menstrual fluid using single-cell RNA sequencing.","abstract":"Menstrual fluid (MF) is an accessible source of large numbers of live cells of high biomedical interest. During menstruation, the female body sheds 35–80ml of MF containing blood and cells (in single cells or in clumps) from the uterine lining, the cervix, the ovaries and the vaginal lining. This rich source of live cells has been previously proposed as a scalable source of live uterine NK cells and mesenchymal stem cells for research and therapy. Despite its potential, knowledge of the cellular composition and relative representation of the multiple reproductive tissues in menstrual fluid is limited. In this study we assay the cell type composition of menstrual fluid using single-cell RNA sequencing.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002553","title":"Pilot_Fetal_Cell_Atlas_RNAseq","description":"As part of the Human Cell Atlas we will study fetal tissue.","abstract":"The HFCA aims to generate a comprehensive profile of these cell types and stated present during the embryo formation. The detailed study of human development will be critical for understanding congenital and childhood disorders, as well as ageing.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-07T09:36:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002554","title":"Genentech - Cell line exome sequencing","description":"Genentech cell line exome study.  A wide variety of cell lines were sequenced.","abstract":"Genentech cell line exome study.  A wide variety of cell lines were sequenced.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-07T17:03:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002555","title":"Plasma pQTLs in INTERVAL cohort","description":"Human pQTLs using UK INTERVAL (Cambridge CEU) plasma samples. pQTL mapping of 3,283 protein analytes assayed using SomaLogic SOMAscan, across 10.6M imputed genetic variants, in 3,301 samples.","abstract":"Human pQTLs using UK INTERVAL (Cambridge CEU) plasma samples. pQTL mapping of 3,283 protein analytes assayed using SomaLogic SOMAscan, across 10.6M imputed genetic variants, in 3,301 samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-10T16:15:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002556","title":"TGF-β attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells.","description":"We examined tumours from a large cohort of patients with metastatic urothelial bladder cancer (mUC) treated with an anti–PD-L1 agent (atezolizumab) and identified major determinants of clinical response and immune escape. Whole transcriptome profiles were generated for 368 patients using TruSeq RNA Access technology (Illumina). Somatic mutations were determined via whole exome sequencing for a subset of these patients.  - Response was associated with CD8+ T effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden (TMB). On the other hand, lack of response was associated with a transforming growth factor β (TGF-β) signature, particularly in patients with CD8+ T cells preferentially residing in collagen-rich matrix surrounding tumours. Integration of these three independent biological features provided the best basis for understanding outcome in this setting. -","abstract":"We examined tumours from a large cohort of patients with metastatic urothelial bladder cancer (mUC) treated with an anti–PD-L1 agent (atezolizumab) and identified major determinants of clinical response and immune escape. Whole transcriptome profiles were generated for 368 patients using TruSeq RNA Access technology (Illumina). Somatic mutations were determined via whole exome sequencing for a subset of these patients.  - Response was associated with CD8+ T effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden (TMB). On the other hand, lack of response was associated with a transforming growth factor β (TGF-β) signature, particularly in patients with CD8+ T cells preferentially residing in collagen-rich matrix surrounding tumours. Integration of these three independent biological features provided the best basis for understanding outcome in this setting. -","study_type":"Other","pubmed_ids":[29443960],"external_links":null,"is_released":true,"released_date":"2017-07-10T19:00:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002557","title":"Copy-number signatures and mutational processes in ovarian carcinoma","description":"This study contains the data underlying our approach for copy-number signature identification in high-grade serous ovarian cancer. The samples studied are part of the BriTROC-1 consortium, a national study into relapsed high-grade serous ovarian cancer. The dataset consists of shallow-whole genome sequencing of 300 samples from 143 patients with match tagged-amplicon sequencing of TP53. The study also contains deeper whole-genome sequencing of 48 cases.","abstract":"This study contains the data underlying our approach for copy-number signature identification in high-grade serous ovarian cancer. The samples studied are part of the BriTROC-1 consortium, a national study into relapsed high-grade serous ovarian cancer. The dataset consists of shallow-whole genome sequencing of 300 samples from 143 patients with match tagged-amplicon sequencing of TP53. The study also contains deeper whole-genome sequencing of 48 cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-10T23:17:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002558","title":"Genomic diversity of the African-descent Makranis of Pakistan","description":"From the eighth century onward, the Indian Ocean was the scene of extensive trade of sub-Saharan African slaves, via sea routes controlled by Muslim Arab and Swahili traders. Several populations in present-day Pakistan and India are thought to be the descendants of such slaves, yet their genetic ancestries and history of admixture and natural selection remain largely undefined. Here we studied the genome-wide diversity of the African-descent Makranis, residing on the Arabian Sea coast of Pakistan, together with that of four neighboring Pakistani populations, to investigate the genetic legacy, population dynamics and tempo of the Indian Ocean slave trade. We show that the Makranis result from an admixture event between local Baluch tribes and Bantu-speaking populations from eastern/southeastern Africa, which we dated to ~300 years ago during the Omani Empire domination. Levels of inbreeding, measured through cumulative runs of homozygosity, were found to be similar across Pakistani populations, suggesting that the admixed Makranis rapidly adopted the traditional practice of endogamous marriages. Finally, we searched for signatures of post-admixture selection at several traits evolving under positive selection, including skin color, lactase persistence and resistance to malaria. We demonstrate that the African-specific Duffy-null blood group — believed to confer resistance against Plasmodium vivax infection — was recently introduced to Pakistan through the slave trade and evolved under positive selection in this vivax malaria-endemic region. Collectively, our study reconstructs the genetic and adaptive history of a neglected episode of the African Diaspora, and illustrates the impact of recent admixture on the diffusion of adaptive traits across human populations.","abstract":"From the eighth century onward, the Indian Ocean was the scene of extensive trade of sub-Saharan African slaves, via sea routes controlled by Muslim Arab and Swahili traders. Several populations in present-day Pakistan and India are thought to be the descendants of such slaves, yet their genetic ancestries and history of admixture and natural selection remain largely undefined. Here we studied the genome-wide diversity of the African-descent Makranis, residing on the Arabian Sea coast of Pakistan, together with that of four neighboring Pakistani populations, to investigate the genetic legacy, population dynamics and tempo of the Indian Ocean slave trade. We show that the Makranis result from an admixture event between local Baluch tribes and Bantu-speaking populations from eastern/southeastern Africa, which we dated to ~300 years ago during the Omani Empire domination. Levels of inbreeding, measured through cumulative runs of homozygosity, were found to be similar across Pakistani populations, suggesting that the admixed Makranis rapidly adopted the traditional practice of endogamous marriages. Finally, we searched for signatures of post-admixture selection at several traits evolving under positive selection, including skin color, lactase persistence and resistance to malaria. We demonstrate that the African-specific Duffy-null blood group — believed to confer resistance against Plasmodium vivax infection — was recently introduced to Pakistan through the slave trade and evolved under positive selection in this vivax malaria-endemic region. Collectively, our study reconstructs the genetic and adaptive history of a neglected episode of the African Diaspora, and illustrates the impact of recent admixture on the diffusion of adaptive traits across human populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-11T09:37:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002559","title":"Exome-wide somatic mutation characterization of small bowel adenocarcinoma","description":"Small intestinal adenocarcinoma (SIA) is a rare and aggressive form of cancer with limited treatment options. To further characterize the somatic mutation landscape of this tumor type, exome sequencing was conducted on a population-based set of SIA samples from all three parts of the small intestine. Archival tissue from 106 tumors with comprehensive clinical patient information entered exome sequencing from a patient series consisting of SIA cases diagnosed in Finland between the years 2003-2011. Paired-end exome sequencing was performed using Illumina HiSeq 4000, and OncodriveFML was used to identify significantly mutated genes from the exome data. Also mutational signature and pathway enrichment analyses were performed.","abstract":"Small intestinal adenocarcinoma (SIA) is a rare and aggressive form of cancer with limited treatment options. To further characterize the somatic mutation landscape of this tumor type, exome sequencing was conducted on a population-based set of SIA samples from all three parts of the small intestine. Archival tissue from 106 tumors with comprehensive clinical patient information entered exome sequencing from a patient series consisting of SIA cases diagnosed in Finland between the years 2003-2011. Paired-end exome sequencing was performed using Illumina HiSeq 4000, and OncodriveFML was used to identify significantly mutated genes from the exome data. Also mutational signature and pathway enrichment analyses were performed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-11T11:06:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002560","title":"Single-cell RNA sequencing reveals cell-type specific eQTLs in peripheral blood mononuclear cells","description":"This proof-of-concept study shows that single-cell RNA sequencing in ~25,000 peripheral blood mononuclear cells (PBMCs) of 45 donors allows for the identification of cell type-specific cis expression quantitative trait loci effects (cis-eQTLs). Moreover, the significant top-eQTL effects show consistent allelic direction (94%) with previously published whole blood deepSAGE data.  These cell type-specific eQTLs may give us additional insight into the downstream consequences of genetic risk factors for immune-mediated diseases.","abstract":"This proof-of-concept study shows that single-cell RNA sequencing in ~25,000 peripheral blood mononuclear cells (PBMCs) of 45 donors allows for the identification of cell type-specific cis expression quantitative trait loci effects (cis-eQTLs). Moreover, the significant top-eQTL effects show consistent allelic direction (94%) with previously published whole blood deepSAGE data.  These cell type-specific eQTLs may give us additional insight into the downstream consequences of genetic risk factors for immune-mediated diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-11T13:47:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002561","title":"Ancient_DNA_from_Lebanon","description":"Sequencing of ancient individuals from Lebanon dating back to the 12th century AD\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Sequences of eight individuals from Lebanon dating back to the 12th century AD and discovered in an archaeological context suggestive of a foreign origin.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002562","title":"Exome sequencing data from two myelosarcomas","description":"Isolated myeloid sarcoma (MS, i.e. acute myeloid leukemia without detectable bone marrow infiltration) is rare and most patients subsequently develop overt AML. We prospectively performed whole exome sequencing of uterine MS, concomitant morphologically normal bone marrow (BM) and subsequently developing AML from two women. Both patients harbored preleukemic clones in the morphologically normal BM, including DNMT3A mutations. In addition, recurrent mutations were identified in the NFE2 gene, a gene not previously associated with AML or isolated MS. Retrospective studies of further MS samples, twelve with and four without preceding or concomitant bone marrow AML, revealed NFE2 mutations in two additional cases, both with isolated MS and prior myeloid malignancies. We conclude that DNMT3A mutated preleukemia may predispose for the frequent bone marrow relapses following isolated MS and that recurrent NFE2 mutations may have a role in the development of isolated MS.","abstract":"Isolated myeloid sarcoma (MS, i.e. acute myeloid leukemia without detectable bone marrow infiltration) is rare and most patients subsequently develop overt AML. We prospectively performed whole exome sequencing of uterine MS, concomitant morphologically normal bone marrow (BM) and subsequently developing AML from two women. Both patients harbored preleukemic clones in the morphologically normal BM, including DNMT3A mutations. In addition, recurrent mutations were identified in the NFE2 gene, a gene not previously associated with AML or isolated MS. Retrospective studies of further MS samples, twelve with and four without preceding or concomitant bone marrow AML, revealed NFE2 mutations in two additional cases, both with isolated MS and prior myeloid malignancies. We conclude that DNMT3A mutated preleukemia may predispose for the frequent bone marrow relapses following isolated MS and that recurrent NFE2 mutations may have a role in the development of isolated MS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-11T18:21:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002563","title":"Placental_biopsy_spiking_test","description":"Pilot study\nThese data are part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"To be added","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002564","title":"Mitochondrial DNA mutations contribute to autism and also to the characteristics of mitochondrial disorders present in patients with autism spectrum disorders","description":"Intellectual disability (ID) is common among autism spectrum disorder (ASD) patients. Also, evidence from many fields of medicine has documented multiple non-CNS physiological abnormalities associated with ASD, suggesting that, in some individuals, ASD arises from systemic, rather than organ-specific abnormalities. Oxidative phosphorylation and mitochondrial dysfunction are frequently reported in ASD and ID and can be due to mitochondrial DNA mutations. Therefore, the objective of the study was to analyze the mitochondrial DNA of ID subjects with ASD (N=98) and without ASD (N=95) to identify putative pathogenic variants that could be associated with ID or ASD.","abstract":"Intellectual disability (ID) is common among autism spectrum disorder (ASD) patients. Also, evidence from many fields of medicine has documented multiple non-CNS physiological abnormalities associated with ASD, suggesting that, in some individuals, ASD arises from systemic, rather than organ-specific abnormalities. Oxidative phosphorylation and mitochondrial dysfunction are frequently reported in ASD and ID and can be due to mitochondrial DNA mutations. Therefore, the objective of the study was to analyze the mitochondrial DNA of ID subjects with ASD (N=98) and without ASD (N=95) to identify putative pathogenic variants that could be associated with ID or ASD.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002565","title":"Genetic history of the Comorian populations.","description":"At the dawn of the second millennium, the expansion of the Indian Ocean trading network aligned with the emergence of an outward-oriented community along the East African coast to create a cosmopolitan cultural and trading zone known as the Swahili Corridor. Based on analyses of genome-wide genotyping data in 140 individuals from coastal Kenya and the Comoros islands, along with 3,477 individuals from the Indian Ocean rim, we reconstruct historical population dynamics showing that the Swahili Corridor is largely an East Bantu genetic continuum. Within this continuity significant gene flows from the Middle East can be seen in the Swahili and Comorians at dates   corresponding to the Islamization of East Africa. However the main external gene flow into insular populations of the Swahili Corridor, such as Comorian and Malagasy groups, came from Island Southeast Asia as early as the 10th century. Remarkably, our results reflect archaeological and linguistic data in suggesting that the Comoros archipelago is the oldest place of contact between Austronesian and African populations in the Swahili Corridor.","abstract":"At the dawn of the second millennium, the expansion of the Indian Ocean trading network aligned with the emergence of an outward-oriented community along the East African coast to create a cosmopolitan cultural and trading zone known as the Swahili Corridor. Based on analyses of genome-wide genotyping data in 140 individuals from coastal Kenya and the Comoros islands, along with 3,477 individuals from the Indian Ocean rim, we reconstruct historical population dynamics showing that the Swahili Corridor is largely an East Bantu genetic continuum. Within this continuity significant gene flows from the Middle East can be seen in the Swahili and Comorians at dates   corresponding to the Islamization of East Africa. However the main external gene flow into insular populations of the Swahili Corridor, such as Comorian and Malagasy groups, came from Island Southeast Asia as early as the 10th century. Remarkably, our results reflect archaeological and linguistic data in suggesting that the Comoros archipelago is the oldest place of contact between Austronesian and African populations in the Swahili Corridor.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-12T16:46:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002566","title":"Combined clinical and gene expression score identifies high-risk individuals among follicular lymphoma patients on immunotherapy","description":"Follicular lymphoma (FL) is usually an indolent malignant B-cell lymphoma, but at least 30% of the patients experience transformation to Diffuse Large B-cell Lymphoma (DLBCL) with inferior survival. Early identification of patients with poor prognosis is essential for tailoring treatment. Here, we describe a network-based integrative analysis of 168 FL-biopsies from 127 patients with long clinical follow-up and transformation status. A distinct shift in expression towards a DLBCL expression phenotype is observed in BTK associated genes in cases with transformation. This shift is present years prior to transformation. An integrated score combining the BTK score and a clinical index is proposed, termed the BTK-FLIPI score. It identifies patients (16%) with very poor prognosis, with median time to progression 21.7 months (95% CI: 14.3-42.6) versus 70.9 months (95% CI: 41.5-95.0) for the remainder. The results suggest BTK as a potential target for treatment of high-risk FL-patients.","abstract":"Follicular lymphoma (FL) is usually an indolent malignant B-cell lymphoma, but at least 30% of the patients experience transformation to Diffuse Large B-cell Lymphoma (DLBCL) with inferior survival. Early identification of patients with poor prognosis is essential for tailoring treatment. Here, we describe a network-based integrative analysis of 168 FL-biopsies from 127 patients with long clinical follow-up and transformation status. A distinct shift in expression towards a DLBCL expression phenotype is observed in BTK associated genes in cases with transformation. This shift is present years prior to transformation. An integrated score combining the BTK score and a clinical index is proposed, termed the BTK-FLIPI score. It identifies patients (16%) with very poor prognosis, with median time to progression 21.7 months (95% CI: 14.3-42.6) versus 70.9 months (95% CI: 41.5-95.0) for the remainder. The results suggest BTK as a potential target for treatment of high-risk FL-patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-13T09:50:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002567","title":"Pilot study for Illumina TST170 NGS panel on cutaneous T cell lymphoma samples","description":"A number of genomic studies using next generation sequencing (NGS) techniques have attempted to understand the underlying genetic basis of cutaneous T-cell lymphoma and found alterations in genes that are involved in T-cell activation, NF-kB and JAK-signal transducer and activator of transcription (STAT) pathways. 8 diagnostic skin biopsy samples (2xplaque, 6xtumour) on FFPE blocks were selected from 8 MF patients (stage IB:n=1, IIB:n=6, IVA2:n=1). An H&amp;E was performed in order to assess percentage of tumor cells, viable cells, necrosis and immune infiltration, to determine the number of slides required for NGS. Freshly cut unstained slides were manually macrodissected prior to DNA and RNA extraction. Targeted deep sequencing was performed using panel of 170 genes associated with common solid tumours (Illumina TruSight Tumour 170 NGS panel). VCF files generated via the Illumina’s Basespace platform.","abstract":"A number of genomic studies using next generation sequencing (NGS) techniques have attempted to understand the underlying genetic basis of cutaneous T-cell lymphoma and found alterations in genes that are involved in T-cell activation, NF-kB and JAK-signal transducer and activator of transcription (STAT) pathways. 8 diagnostic skin biopsy samples (2xplaque, 6xtumour) on FFPE blocks were selected from 8 MF patients (stage IB:n=1, IIB:n=6, IVA2:n=1). An H&amp;E was performed in order to assess percentage of tumor cells, viable cells, necrosis and immune infiltration, to determine the number of slides required for NGS. Freshly cut unstained slides were manually macrodissected prior to DNA and RNA extraction. Targeted deep sequencing was performed using panel of 170 genes associated with common solid tumours (Illumina TruSight Tumour 170 NGS panel). VCF files generated via the Illumina’s Basespace platform.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-13T14:32:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002568","title":"KLB mutations in congenital hypogonadotropic hypogonadism","description":"To test if patients with congenital hypogonadotropic hypogonadism harbor mutations in FGF21 and KLB (encoding the co-receptor of FGF21)","abstract":"To test if patients with congenital hypogonadotropic hypogonadism harbor mutations in FGF21 and KLB (encoding the co-receptor of FGF21)","study_type":"Other","pubmed_ids":[28754744],"external_links":null,"is_released":true,"released_date":"2017-07-13T14:48:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002569","title":"Genetic history of the Swahili population","description":"At the dawn of the second millennium, the expansion of the Indian Ocean trading network aligned with the emergence of an outward-oriented community along the East African coast to create a cosmopolitan cultural and trading zone known as the Swahili Corridor. Based on analyses of genome-wide genotyping data in 140 individuals from coastal Kenya and the Comoros islands, along with 3,477 individuals from the Indian Ocean rim, we reconstruct historical population dynamics showing that the Swahili Corridor is largely an East Bantu genetic continuum. Within this continuity significant gene flows from the Middle East can be seen in the Swahili and Comorians at dates   corresponding to the Islamization of East Africa. However the main external gene flow into insular populations of the Swahili Corridor, such as Comorian and Malagasy groups, came from Island Southeast Asia as early as the 10th century. Remarkably, our results reflect archaeological and linguistic data in suggesting that the Comoros archipelago is the oldest place of contact between Austronesian and African populations in the Swahili Corridor.","abstract":"At the dawn of the second millennium, the expansion of the Indian Ocean trading network aligned with the emergence of an outward-oriented community along the East African coast to create a cosmopolitan cultural and trading zone known as the Swahili Corridor. Based on analyses of genome-wide genotyping data in 140 individuals from coastal Kenya and the Comoros islands, along with 3,477 individuals from the Indian Ocean rim, we reconstruct historical population dynamics showing that the Swahili Corridor is largely an East Bantu genetic continuum. Within this continuity significant gene flows from the Middle East can be seen in the Swahili and Comorians at dates   corresponding to the Islamization of East Africa. However the main external gene flow into insular populations of the Swahili Corridor, such as Comorian and Malagasy groups, came from Island Southeast Asia as early as the 10th century. Remarkably, our results reflect archaeological and linguistic data in suggesting that the Comoros archipelago is the oldest place of contact between Austronesian and African populations in the Swahili Corridor.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-13T15:34:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002570","title":"Progression to AML is predictable and distinct from age related clonal hematopoiesis","description":"To examine the occurrence of somatic mutations prior to the development of acute myeloid leukemia, we undertook deep ECS (estimated limit of detection 1 mutation in 2500 cells) of 261 AML associated genes in 96 pre-AML cases and 420 age and gender-matched healthy controls of an average of 3853 unique DNA molecules covering each of the 1.19M bases spanning the target gene panel. The findings suggest that the development of clonal hematopoiesis and accumulation of somatic mutations is distinct and accelerated in pre-AML cases compared to healthy individuals","abstract":"To examine the occurrence of somatic mutations prior to the development of acute myeloid leukemia, we undertook deep ECS (estimated limit of detection 1 mutation in 2500 cells) of 261 AML associated genes in 96 pre-AML cases and 420 age and gender-matched healthy controls of an average of 3853 unique DNA molecules covering each of the 1.19M bases spanning the target gene panel. The findings suggest that the development of clonal hematopoiesis and accumulation of somatic mutations is distinct and accelerated in pre-AML cases compared to healthy individuals","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-13T16:52:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002571","title":"Identification  of cis-regulatory  mutations  generating de  novo  edges  in personalized cancer gene regulatory networks","description":"The identification of functional non-coding mutations is a key challenge in the field of genomics. Here we introduce μ-cisTarget to filter, annotate and prioritize cis-regulatory mutations based on their putative effect on the underlying ‘personal’ gene regulatory network. We validated μ-cisTarget by re-analyzing the TAL1 and LMO1 enhancer mutations in T-ALL, and the TERT promoter mutation in melanoma. Next, we re-sequenced the full genome of ten cancer cell lines and used matched transcriptome data and motif discovery to identify master regulators with de novo binding sites that result in the up-regulation of nearby oncogenic drivers.","abstract":"The identification of functional non-coding mutations is a key challenge in the field of genomics. Here we introduce μ-cisTarget to filter, annotate and prioritize cis-regulatory mutations based on their putative effect on the underlying ‘personal’ gene regulatory network. We validated μ-cisTarget by re-analyzing the TAL1 and LMO1 enhancer mutations in T-ALL, and the TERT promoter mutation in melanoma. Next, we re-sequenced the full genome of ten cancer cell lines and used matched transcriptome data and motif discovery to identify master regulators with de novo binding sites that result in the up-regulation of nearby oncogenic drivers.","study_type":"Other","pubmed_ids":[28854983],"external_links":null,"is_released":true,"released_date":"2017-07-17T16:57:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002572","title":"eQTL_Influenza_H1N1","description":"Samples ascertained as part of the HIRD study (see https://www.nature.com/ni/journal/v17/n2/pdf/ni.3328.pdf). These data include genotype and RNA-seq data generated across a subset of these samples, both before and longitudinally after vaccination with the swine flu vaccine, Pandemrix.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Samples ascertained as part of the HIRD study (see https://www.nature.com/ni/journal/v17/n2/pdf/ni.3328.pdf). These data include genotype and RNA-seq data generated across a subset of these samples, both before and longitudinally after vaccination with the swine flu vaccine, Pandemrix.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002573","title":"eQTL_Influenza_H1N1","description":"Samples ascertained as part of the HIRD study (see https://www.nature.com/ni/journal/v17/n2/pdf/ni.3328.pdf). These data include genotype and RNA-seq data generated across a subset of these samples, both before and longitudinally after vaccination with the swine flu vaccine, Pandemrix.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Samples ascertained as part of the HIRD study (see https://www.nature.com/ni/journal/v17/n2/pdf/ni.3328.pdf). These data include genotype and RNA-seq data generated across a subset of these samples, both before and longitudinally after vaccination with the swine flu vaccine, Pandemrix.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002574","title":"G_T_seq_on_single_human_neuronal_nuclei___DNA","description":"Single neuronal nuclei are isolated from deceased donors. G&amp;T-seq will be performed to obtain genome and transcriptome information from the same cell.","abstract":"DNA sequencing of single human neurons willl enable the comprehension of the developmental relations between these cells and reveal any active mutational processes. Moreover, the expression profiles will be used to associate these characteristics with functional cell states.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002575","title":"G_T_seq_on_single_human_neuronal_nuclei___RNA","description":"Single neuronal nuclei are isolated from deceased donors. G&amp;T-seq will be performed to obtain genome and transcriptome information from the same cell.","abstract":"DNA sequencing of single human neurons willl enable the comprehension of the developmental relations between these cells and reveal any active mutational processes. Moreover, the expression profiles will be used to associate these characteristics with functional cell states.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002576","title":"Comparative genomics research for Chinese colorectal cancer","description":"In order to clarify the mechanisms of genesis and development of colorectal carcinoma, in this study, we performed comparative genomics research in Chinese colorectal cancer at various clinical stage via whole exon sequencing or whole genome sequencing. Comparative bioinformatical analysis was perform to find the difference on somatic single-nucleotide variants, short insert/deletion variants, genomic structural variants, and copy number variants between cancer tissue and normal tissue, or among cancer tissues at various clinical stages.","abstract":"In order to clarify the mechanisms of genesis and development of colorectal carcinoma, in this study, we performed comparative genomics research in Chinese colorectal cancer at various clinical stage via whole exon sequencing or whole genome sequencing. Comparative bioinformatical analysis was perform to find the difference on somatic single-nucleotide variants, short insert/deletion variants, genomic structural variants, and copy number variants between cancer tissue and normal tissue, or among cancer tissues at various clinical stages.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-19T06:10:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002577","title":"Direct Detection of Early-stage Cancers Using Circulating Tumor DNA","description":"Early detection and intervention are likely to be the most effective means for reducing morbidity and mortality of human cancer. However, development of methods for noninvasive detection of early-stage tumors has remained a challenge. We have developed an approach called targeted error correction sequencing (TEC-Seq) that allows ultrasensitive direct evaluation of sequence changes in circulating cell-free DNA using massively parallel sequencing. We have used this approach to examine 58 cancer-related genes encompassing 81 kb. Analysis of plasma from 44 healthy individuals identified genomic changes related to clonal hematopoiesis in 16% of asymptomatic individuals but no alterations in driver genes related to solid cancers. Evaluation of 200 patients with colorectal, breast, lung, or ovarian cancer detected somatic mutations in the plasma of 71, 59, 59, and 68%, respectively, of patients with stage I or II disease. Analyses of mutations in the circulation revealed high concordance with alterations in the tumors of these patients. In patients with resectable colorectal cancers, higher amounts of preoperative circulating tumor DNA were associated with disease recurrence and decreased overall survival. These analyses provide a broadly applicable approach for noninvasive detection of early-stage tumors that may be useful for screening and management of patients with cancer.","abstract":"Early detection and intervention are likely to be the most effective means for reducing morbidity and mortality of human cancer. However, development of methods for noninvasive detection of early-stage tumors has remained a challenge. We have developed an approach called targeted error correction sequencing (TEC-Seq) that allows ultrasensitive direct evaluation of sequence changes in circulating cell-free DNA using massively parallel sequencing. We have used this approach to examine 58 cancer-related genes encompassing 81 kb. Analysis of plasma from 44 healthy individuals identified genomic changes related to clonal hematopoiesis in 16% of asymptomatic individuals but no alterations in driver genes related to solid cancers. Evaluation of 200 patients with colorectal, breast, lung, or ovarian cancer detected somatic mutations in the plasma of 71, 59, 59, and 68%, respectively, of patients with stage I or II disease. Analyses of mutations in the circulation revealed high concordance with alterations in the tumors of these patients. In patients with resectable colorectal cancers, higher amounts of preoperative circulating tumor DNA were associated with disease recurrence and decreased overall survival. These analyses provide a broadly applicable approach for noninvasive detection of early-stage tumors that may be useful for screening and management of patients with cancer.","study_type":"Other","pubmed_ids":[28814544],"external_links":null,"is_released":true,"released_date":"2017-07-19T13:23:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002578","title":"Whole genome shotgun sequencing and somatic mutations data in Hepatocellular carcinoma","description":"Hepatocellular carcinoma (HCC) is the most common malignancy of the liver. Genomic analysis is conducted to identify genetic alterations in driver genes which are all druggable targets for cancer therapy.","abstract":"Hepatocellular carcinoma (HCC) is the most common malignancy of the liver. Genomic analysis is conducted to identify genetic alterations in driver genes which are all druggable targets for cancer therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-20T05:49:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002579","title":"Combination Therapies for Personalised Cancer Medicine in 11-18","description":"This study involves mutagenizing 11-18 with ENU to identify those mutations which engender resistance to targeted treatment.\nIn the last decade we have begun to move towards the use of targeted therapeutics in the clinic, often resulting in dramatic response rates in cancer patients. However, clinical experience has demonstrated time and time again that such responses are invariably followed by the development of drug resistance. Identification of the underlying mechanisms may enable us to reverse such resistance. Traditional methods of modelling this resistance in vitro can lead to a plethora of potential resistance mechanisms that can be difficult to decipher.","abstract":"This study involves mutagenizing 11-18 with ENU to identify those mutations which engender resistance to targeted treatment.\nIn the last decade we have begun to move towards the use of targeted therapeutics in the clinic, often resulting in dramatic response rates in cancer patients. However, clinical experience has demonstrated time and time again that such responses are invariably followed by the development of drug resistance. Identification of the underlying mechanisms may enable us to reverse such resistance. Traditional methods of modelling this resistance in vitro can lead to a plethora of potential resistance mechanisms that can be difficult to decipher.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-20T13:02:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002580","title":"Whole exome and genome sequencing for 50 pancreatic cancer patient and matched metastases.","description":"Pancreatic cancer is a highly lethal disease which carries a dismal prognosis. Therapeutic options are limited, and the only potentially curative option remains surgery. Previous large-scale sequencing studies have focused on the genetics of the primary tumor. We performed whole genome and whole exome sequencing on 341 primary and metastatic samples from 50 patients. Stages of diagnosis range from resectable (Stage I/II) to widely disseminated metastatic disease (Stage IV). In our cohort, we detected 12,255 high quality non-silent variants with 1,244 occurring in two or more patients. Further in-depth analysis revealed 27 frequently mutated genes. Approximately half, including KRAS, TP53, CDKN2A, and SMAD4, have been previously reported to be deleterious. Other involved pathways include cell growth/proliferation (CDS1, ITGB1BP1), cell degradation/apoptosis (TRIM13, THADA, MLEC), and local tumor infiltration via cell-cell adhesion (LAMP1).","abstract":"Pancreatic cancer is a highly lethal disease which carries a dismal prognosis. Therapeutic options are limited, and the only potentially curative option remains surgery. Previous large-scale sequencing studies have focused on the genetics of the primary tumor. We performed whole genome and whole exome sequencing on 341 primary and metastatic samples from 50 patients. Stages of diagnosis range from resectable (Stage I/II) to widely disseminated metastatic disease (Stage IV). In our cohort, we detected 12,255 high quality non-silent variants with 1,244 occurring in two or more patients. Further in-depth analysis revealed 27 frequently mutated genes. Approximately half, including KRAS, TP53, CDKN2A, and SMAD4, have been previously reported to be deleterious. Other involved pathways include cell growth/proliferation (CDS1, ITGB1BP1), cell degradation/apoptosis (TRIM13, THADA, MLEC), and local tumor infiltration via cell-cell adhesion (LAMP1).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002581","title":"Molecular profiling of MBD4-deficient acute myeloid leukaemia","description":"We describe two cases of MBD4-deficient acute myeloid leukaemia (AML). Clinical samples were used for molecular analysis, including genomic profiling (genome and exomes), methylation analysis (RRBS) and transcriptional profiling (RNA-sequencing). An analysis and methodological description has been published: “MBD4 guards against methylation damage and germline deficiency predisposes to clonal hematopoiesis and early-onset AML” [PMID: 30049810]","abstract":"We describe two cases of MBD4-deficient acute myeloid leukaemia (AML). Clinical samples were used for molecular analysis, including genomic profiling (genome and exomes), methylation analysis (RRBS) and transcriptional profiling (RNA-sequencing). An analysis and methodological description has been published: “MBD4 guards against methylation damage and germline deficiency predisposes to clonal hematopoiesis and early-onset AML” [PMID: 30049810]","study_type":"Other","pubmed_ids":[30049810],"external_links":null,"is_released":true,"released_date":"2017-07-21T01:55:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002582","title":"Inhibiton of the GABPB1L-containing GABP tetramer is sufficient to reverse replicative immortality in TERT promoter mutant glioblastoma cells.","description":"Over 50 types of cancer acquire TERT promoter mutations. These single point mutations reactivate telomerase, allowing for indefinite maintenance of telomere length and enabling cellular immortalization. The transcription factor binding site created by the point mutations specifically recruit the ETS factor GABP, a multimeric transcription factor composed of the GABPα and GABPβ subunits. GABP can form two functionally independent transcription factor species – a dimer or a tetramer – depending on which of the structurally distinct GABPβ isoforms is incorporated into the complex. In this study, we show that genetic disruption of GABPβ1L, a tetramer forming isoform of GABPβ that is dispensable in normal development, results in TERT silencing in a TERT promoter mutation dependent manner. Failure to activate TERT expression by GABPβ1L culminates in telomere dysfunction, DNA damage, and mitotic cell death exclusively in TERT promoter mutant cells. Furthermore, exogenous expression of TERT is sufficient to prevent telomere degradation and loss of cell viability in GABPβ1L-reduced lines bearing the mutant TERT promoter. Orthotopic injection of tetramer-deficient mutant TERT promoter GBM cells rendered lower tumor burden and prolonged the overall survival of the tumor-bearing mice. These results highlight the potentially widespread role of GABPB1L in enabling replicative immortality of TERT promoter cancers.","abstract":"Over 50 types of cancer acquire TERT promoter mutations. These single point mutations reactivate telomerase, allowing for indefinite maintenance of telomere length and enabling cellular immortalization. The transcription factor binding site created by the point mutations specifically recruit the ETS factor GABP, a multimeric transcription factor composed of the GABPα and GABPβ subunits. GABP can form two functionally independent transcription factor species – a dimer or a tetramer – depending on which of the structurally distinct GABPβ isoforms is incorporated into the complex. In this study, we show that genetic disruption of GABPβ1L, a tetramer forming isoform of GABPβ that is dispensable in normal development, results in TERT silencing in a TERT promoter mutation dependent manner. Failure to activate TERT expression by GABPβ1L culminates in telomere dysfunction, DNA damage, and mitotic cell death exclusively in TERT promoter mutant cells. Furthermore, exogenous expression of TERT is sufficient to prevent telomere degradation and loss of cell viability in GABPβ1L-reduced lines bearing the mutant TERT promoter. Orthotopic injection of tetramer-deficient mutant TERT promoter GBM cells rendered lower tumor burden and prolonged the overall survival of the tumor-bearing mice. These results highlight the potentially widespread role of GABPB1L in enabling replicative immortality of TERT promoter cancers.","study_type":"Other","pubmed_ids":[30205050],"external_links":null,"is_released":true,"released_date":"2017-07-21T17:15:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002583","title":"APCDR Durban Diabetes Study (DDS)","description":"Population-based cross-sectional survey using multistage cluster sampling of adults aged ≥18 years in Durban (eThekwini municipality), KwaZulu-Natal","abstract":"Population-based cross-sectional survey using multistage cluster sampling of adults aged ≥18 years in Durban (eThekwini municipality), KwaZulu-Natal","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002584","title":"APCDR Diabetes Case Control Study","description":"Collection of type 2 diabetes cases of Zulu descent for studies of the genetic basis of diabetes in African populations.","abstract":"Collection of type 2 diabetes cases of Zulu descent for studies of the genetic basis of diabetes in African populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002585","title":"A transgenerational MMACHC epimutation illustrates a new mechanism for inborn errors of metabolism","description":"Up to now, the epimutations reported in man have been somatic, without germlinetransmission. We report the transgenerational transmission of a constitutional epimutation inthe cblC class of inborn error of vitamin B12 metabolism that we named epi-cblC. Subjectscarry, in trans, a heterozygous MMACHC mutation and a promoter epimutation, detectable inblood, fibroblasts and sperm; the epimutation was transmitted through three generations. 5-Azacytidine restored the MMACHC expression in fibroblasts. MMACHC is flanked byCCDC163P and PRDX1, which are in the opposite orientation. Genome-wide sequencingidentified PRDX1 mutations that forced antisense transcription of MMACHC, resulting in aH3K36me3 mark in the promoter. The silencing of PRDX1 transcription produced a partialhypomethylation of the epiallele and restored the expression of MMCHC. The example of epicblC shows the need to look for compound epigenetic/genetic heterozygosity in patients with typical disease manifestation and genetic heterozygosity in disease-causing genes located in other gene trios.","abstract":"Up to now, the epimutations reported in man have been somatic, without germlinetransmission. We report the transgenerational transmission of a constitutional epimutation inthe cblC class of inborn error of vitamin B12 metabolism that we named epi-cblC. Subjectscarry, in trans, a heterozygous MMACHC mutation and a promoter epimutation, detectable inblood, fibroblasts and sperm; the epimutation was transmitted through three generations. 5-Azacytidine restored the MMACHC expression in fibroblasts. MMACHC is flanked byCCDC163P and PRDX1, which are in the opposite orientation. Genome-wide sequencingidentified PRDX1 mutations that forced antisense transcription of MMACHC, resulting in aH3K36me3 mark in the promoter. The silencing of PRDX1 transcription produced a partialhypomethylation of the epiallele and restored the expression of MMCHC. The example of epicblC shows the need to look for compound epigenetic/genetic heterozygosity in patients with typical disease manifestation and genetic heterozygosity in disease-causing genes located in other gene trios.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002586","title":"Transcriptome analysis in very preterm infants with chronic lung disease after birth","description":"Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity and is characterized by impaired alveolar and vascular development. The aim of the study was to identify early BPD-relevant pathways by applying whole genome transcriptional profiling combined with protein measurements from umbilical arterial blood samples of preterm infants with and without BPD. Only newborn infants &lt;32 weeks gestational age (GA) were prospectively included in this study. Blood was obtained from an indwelling umbilical artery catheter at birth and after 72 hours after birth and subjected to gene expression analysis using the Codelink Human I 10k Bioarray and the the Codelink Human Whole Genome Bioarray. The study reveals a monocyte-centered immune response at birth characterizing preterm infants later developing BPD. The findings provide potential markers for early risk stratification in the preterm infant with respect to the development of chronic pulmonary disease and may subsequently enable the development of new treatment strategies in this high risk patient cohort.","abstract":"Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity and is characterized by impaired alveolar and vascular development. The aim of the study was to identify early BPD-relevant pathways by applying whole genome transcriptional profiling combined with protein measurements from umbilical arterial blood samples of preterm infants with and without BPD. Only newborn infants &lt;32 weeks gestational age (GA) were prospectively included in this study. Blood was obtained from an indwelling umbilical artery catheter at birth and after 72 hours after birth and subjected to gene expression analysis using the Codelink Human I 10k Bioarray and the the Codelink Human Whole Genome Bioarray. The study reveals a monocyte-centered immune response at birth characterizing preterm infants later developing BPD. The findings provide potential markers for early risk stratification in the preterm infant with respect to the development of chronic pulmonary disease and may subsequently enable the development of new treatment strategies in this high risk patient cohort.","study_type":"Other","pubmed_ids":[28923828],"external_links":null,"is_released":true,"released_date":"2017-07-24T10:03:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002587","title":"ITCC PEDIATRIC PRECLINICAL POC PLATFORM (ITCC-P4)","description":"Cancer remains the leading cause of disease-related death in children. For the ~25% of children who experience relapses of their malignant solid tumors, usually after very intensive first-line therapy, curative treatment options are scarce. Preclinical drug testing to identify promising treatment options that match the molecular make-up of the tumor is hampered by the fact that i) molecular genetic data on pediatric solid tumors from relapsed patients and thus our understanding of tumor evolution and therapy resistance are very limited to date and ii) for many of the high-risk entities, no appropriate and molecularly well characterized patient-derived models and/or genetic mouse models are currently available. Thus, quality-assured upfront preclinical testing of novel molecularly targeted compounds in a (saturated) repertoire of well-characterized models will establish the basis to increase therapeutic successes of these drugs in children with solid malignancies. Since these tumors are overall genetically much less complex than their adult counterparts, it is anticipated that it will be easier to identify powerful predictive biomarkers to allow for accurate matching of targets and drugs.To address this high but as yet unmet clinical need, the main objectives for this preclinical platform project are the following:• To establish a representative collection of patient-derived in vitro and in vivo models (target: n=400) as well as genetic mouse models (target: maximum of 15 spread out across multiple tumor types) of the most common pediatric solid high-risk entities including a significant proportion of models from relapses.• To molecularly characterize and to quality-assess the models as well as the matching primary tumor samples and germline controls with state-of-the-art molecular diagnostic tools.• To enable regulatory filings in the EU through the development of comprehensive preclinical data packages necessary to move drugs into clinical trials for children with solid tumors.• To prioritize pediatric drug development using existing collections of molecular data for systematic target reports, followed by in vivo drug testing in faithful disease models including pharmacokinetics and pharmacodynamicswhere necessary (e.g., brain penetration). In vivo drug testing will also include at least three standard-of care-drugs for all models as a baseline for comparisons.• To identify suitable biomarkers for future clinical stratification of patients across entities.• Ultimately, the establishment of the ITCC-P4 platform over the long term will overcome a long-standing gap by enabling thorough molecular characterization of high-risk pediatric malignancies coupled with standardized preclinical testing procedures, and will thus greatly expedite the development of more precise and efficacious drugs for this patient group. Developing this platform as a public-private partnership will create a model for collaboration that can hopefully be extended to other types of cancer entities and patient groups.","abstract":"Cancer remains the leading cause of disease-related death in children. For the ~25% of children who experience relapses of their malignant solid tumors, usually after very intensive first-line therapy, curative treatment options are scarce. Preclinical drug testing to identify promising treatment options that match the molecular make-up of the tumor is hampered by the fact that i) molecular genetic data on pediatric solid tumors from relapsed patients and thus our understanding of tumor evolution and therapy resistance are very limited to date and ii) for many of the high-risk entities, no appropriate and molecularly well characterized patient-derived models and/or genetic mouse models are currently available. Thus, quality-assured upfront preclinical testing of novel molecularly targeted compounds in a (saturated) repertoire of well-characterized models will establish the basis to increase therapeutic successes of these drugs in children with solid malignancies. Since these tumors are overall genetically much less complex than their adult counterparts, it is anticipated that it will be easier to identify powerful predictive biomarkers to allow for accurate matching of targets and drugs.To address this high but as yet unmet clinical need, the main objectives for this preclinical platform project are the following:• To establish a representative collection of patient-derived in vitro and in vivo models (target: n=400) as well as genetic mouse models (target: maximum of 15 spread out across multiple tumor types) of the most common pediatric solid high-risk entities including a significant proportion of models from relapses.• To molecularly characterize and to quality-assess the models as well as the matching primary tumor samples and germline controls with state-of-the-art molecular diagnostic tools.• To enable regulatory filings in the EU through the development of comprehensive preclinical data packages necessary to move drugs into clinical trials for children with solid tumors.• To prioritize pediatric drug development using existing collections of molecular data for systematic target reports, followed by in vivo drug testing in faithful disease models including pharmacokinetics and pharmacodynamicswhere necessary (e.g., brain penetration). In vivo drug testing will also include at least three standard-of care-drugs for all models as a baseline for comparisons.• To identify suitable biomarkers for future clinical stratification of patients across entities.• Ultimately, the establishment of the ITCC-P4 platform over the long term will overcome a long-standing gap by enabling thorough molecular characterization of high-risk pediatric malignancies coupled with standardized preclinical testing procedures, and will thus greatly expedite the development of more precise and efficacious drugs for this patient group. Developing this platform as a public-private partnership will create a model for collaboration that can hopefully be extended to other types of cancer entities and patient groups.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002588","title":"Systematic kinase inhibitor profiling identifies CDK9 as a synthetic lethal target in NUT midline carcinoma","description":"Kinase inhibitors represent the backbone of targeted cancer therapy, yet only a limited number of oncogenic drivers are directly druggable. By interrogating the activity of 1,505 kinase inhibitors we found that BRD4-NUT-rearranged NUT midline carcinoma (NMC) cells are specifically killed by CDK9 inhibition (CDK9i) and exhibit a unique dependency on CDK9 and Cyclin-T1 expression. We show that CDK9i leads to robust induction of apoptosis and of markers of DNA damage response in NMC cells. While both CDK9i and bromodomain inhibition over time result in reduced Myc protein expression, only bromodomain inhibition induces cell differentiation and a p21-induced cell cycle arrest in these cells. Finally, RNA-Seq and ChIP-based analyses reveal a BRD4-NUT specific CDK9i-induced perturbation of transcriptional elongation. Thus, our data provide a mechanistic basis for the genotype-dependent vulnerability of NUT midline carcinoma cells to CDK9i that may be of relevance for the development of targeted therapies for NMC patients.","abstract":"Kinase inhibitors represent the backbone of targeted cancer therapy, yet only a limited number of oncogenic drivers are directly druggable. By interrogating the activity of 1,505 kinase inhibitors we found that BRD4-NUT-rearranged NUT midline carcinoma (NMC) cells are specifically killed by CDK9 inhibition (CDK9i) and exhibit a unique dependency on CDK9 and Cyclin-T1 expression. We show that CDK9i leads to robust induction of apoptosis and of markers of DNA damage response in NMC cells. While both CDK9i and bromodomain inhibition over time result in reduced Myc protein expression, only bromodomain inhibition induces cell differentiation and a p21-induced cell cycle arrest in these cells. Finally, RNA-Seq and ChIP-based analyses reveal a BRD4-NUT specific CDK9i-induced perturbation of transcriptional elongation. Thus, our data provide a mechanistic basis for the genotype-dependent vulnerability of NUT midline carcinoma cells to CDK9i that may be of relevance for the development of targeted therapies for NMC patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-25T11:43:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002589","title":"High Grade Serous Ovarian Carcinomas Originate in the Fallopian Tube","description":"High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian cancer and has a poor outcome.  It has been proposed that fallopian tube cancers may be precursors of HGSOC but evolutionary evidence for this hypothesis has been limited.  To provide insights into the origins of HGSOC, we We performed whole-exome sequence and copy number analyses of laser-capture microdissected fallopian tube lesions (p53 signatures, serous tubal intraepithelial carcinomas (STICs), and fallopian tube carcinomas), ovarian cancers, and metastases from nine patients with HGSOC.  The majority of tumor-specific sequence and structural alterations in ovarian cancers were present in STICs, including those affecting TP53, BRCA1, BRCA2 or PTEN genes. An eEvolutionary analyseis revealed that p53 signatures and STICs were are the precursors of ovarian carcinoma which in turn gave rise to metastatic lesionsand identify a.  In one patient we identified a second STIC as a metastasis in the fallopian tube opposite from the affected ovary.  These analyses revealed a window of seven years between the development of a STIC and the initiation of ovarian carcinomas, with development of metastases following rapidly thereafter.  Our results provide insights into the etiology of ovarian cancer and have implications for the prevention, early detection and therapeutic intervention of this disease.","abstract":"High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian cancer and has a poor outcome.  It has been proposed that fallopian tube cancers may be precursors of HGSOC but evolutionary evidence for this hypothesis has been limited.  To provide insights into the origins of HGSOC, we We performed whole-exome sequence and copy number analyses of laser-capture microdissected fallopian tube lesions (p53 signatures, serous tubal intraepithelial carcinomas (STICs), and fallopian tube carcinomas), ovarian cancers, and metastases from nine patients with HGSOC.  The majority of tumor-specific sequence and structural alterations in ovarian cancers were present in STICs, including those affecting TP53, BRCA1, BRCA2 or PTEN genes. An eEvolutionary analyseis revealed that p53 signatures and STICs were are the precursors of ovarian carcinoma which in turn gave rise to metastatic lesionsand identify a.  In one patient we identified a second STIC as a metastasis in the fallopian tube opposite from the affected ovary.  These analyses revealed a window of seven years between the development of a STIC and the initiation of ovarian carcinomas, with development of metastases following rapidly thereafter.  Our results provide insights into the etiology of ovarian cancer and have implications for the prevention, early detection and therapeutic intervention of this disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-25T16:43:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002590","title":"High Grade Serous Ovarian Carcinomas Originate in the Fallopian Tube","description":"High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian cancer and has a poor outcome.  It has been proposed that fallopian tube cancers may be precursors of HGSOC but evolutionary evidence for this hypothesis has been limited.  To provide insights into the origins of HGSOC, we We performed whole-exome sequence and copy number analyses of laser-capture microdissected fallopian tube lesions (p53 signatures, serous tubal intraepithelial carcinomas (STICs), and fallopian tube carcinomas), ovarian cancers, and metastases from nine patients with HGSOC.  The majority of tumor-specific sequence and structural alterations in ovarian cancers were present in STICs, including those affecting TP53, BRCA1, BRCA2 or PTEN genes. An eEvolutionary analyseis revealed that p53 signatures and STICs were are the precursors of ovarian carcinoma which in turn gave rise to metastatic lesionsand identify a.  In one patient we identified a second STIC as a metastasis in the fallopian tube opposite from the affected ovary.  These analyses revealed a window of seven years between the development of a STIC and the initiation of ovarian carcinomas, with development of metastases following rapidly thereafter.  Our results provide insights into the etiology of ovarian cancer and have implications for the prevention, early detection and therapeutic intervention of this disease.","abstract":"High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian cancer and has a poor outcome.  It has been proposed that fallopian tube cancers may be precursors of HGSOC but evolutionary evidence for this hypothesis has been limited.  To provide insights into the origins of HGSOC, we We performed whole-exome sequence and copy number analyses of laser-capture microdissected fallopian tube lesions (p53 signatures, serous tubal intraepithelial carcinomas (STICs), and fallopian tube carcinomas), ovarian cancers, and metastases from nine patients with HGSOC.  The majority of tumor-specific sequence and structural alterations in ovarian cancers were present in STICs, including those affecting TP53, BRCA1, BRCA2 or PTEN genes. An eEvolutionary analyseis revealed that p53 signatures and STICs were are the precursors of ovarian carcinoma which in turn gave rise to metastatic lesionsand identify a.  In one patient we identified a second STIC as a metastasis in the fallopian tube opposite from the affected ovary.  These analyses revealed a window of seven years between the development of a STIC and the initiation of ovarian carcinomas, with development of metastases following rapidly thereafter.  Our results provide insights into the etiology of ovarian cancer and have implications for the prevention, early detection and therapeutic intervention of this disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002591","title":"Genes associated with pancreas development and function maintain open chromatin in iPSCs generated from human pancreatic beta cells","description":"Current in-vitro islet differentiation protocols suffer from heterogeneity and low efficiency. Induced-pluripotent stem cells (iPSCs) derived from pancreatic beta-cells (BiPSCs) preferentially differentiate towards endocrine pancreas-like cells versus those from fibroblasts (FiPSCs). We interrogated genome-wide open chromatin in BiPSCs and FiPSCs via ATAC-seq, and identified ~8.3k significant, differential open chromatin sites (DOCS) between the two iPSC subtypes (FDR&lt;0.05). DOCS where chromatin was more accessible in BiPSCs (Bi-DOCS) were significantly enriched for known regulators of endodermal development, including bivalent and weak enhancers, and FOXA2 binding sites (FDR&lt;0.05). Bi-DOCS were associated with genes related to pancreas development and beta-cell function, including transcription factors mutated in monogenic diabetes (PDX1, NKX2-2, HNF1A; FDR&lt;0.05). Moreover, Bi-DOCS correlated with enhanced gene expression in BiPSC-derived definitive endoderm and pancreatic progenitor cells. Bi-DOCS therefore highlight genes and pathways governing islet-lineage commitment, which can be exploited for differentiation protocol optimisation, diabetes disease modelling, and therapeutic purposes.","abstract":"Current in-vitro islet differentiation protocols suffer from heterogeneity and low efficiency. Induced-pluripotent stem cells (iPSCs) derived from pancreatic beta-cells (BiPSCs) preferentially differentiate towards endocrine pancreas-like cells versus those from fibroblasts (FiPSCs). We interrogated genome-wide open chromatin in BiPSCs and FiPSCs via ATAC-seq, and identified ~8.3k significant, differential open chromatin sites (DOCS) between the two iPSC subtypes (FDR&lt;0.05). DOCS where chromatin was more accessible in BiPSCs (Bi-DOCS) were significantly enriched for known regulators of endodermal development, including bivalent and weak enhancers, and FOXA2 binding sites (FDR&lt;0.05). Bi-DOCS were associated with genes related to pancreas development and beta-cell function, including transcription factors mutated in monogenic diabetes (PDX1, NKX2-2, HNF1A; FDR&lt;0.05). Moreover, Bi-DOCS correlated with enhanced gene expression in BiPSC-derived definitive endoderm and pancreatic progenitor cells. Bi-DOCS therefore highlight genes and pathways governing islet-lineage commitment, which can be exploited for differentiation protocol optimisation, diabetes disease modelling, and therapeutic purposes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-25T23:17:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002592","title":"Integration of human pancreatic islet genomic data refines regulatory mechanisms at Type 2 Diabetes susceptibility loci","description":"Human genetic studies have emphasised the dominant contribution of pancreatic islet dysfunction to development of Type 2 Diabetes (T2D). However, limited annotation of the islet epigenome has constrained efforts to define the molecular mechanisms mediating the, largely regulatory, signals revealed by Genome-Wide Association Studies (GWAS). We characterised patterns of chromatin accessibility (ATAC-seq, n=17) and DNA methylation (whole-genome bisulphite sequencing, n=10) in human islets, generating high-resolution chromatin state maps through integration with established ChIP-seq marks. We found enrichment of GWAS signals for T2D and fasting glucose was concentrated in subsets of islet enhancers characterised by open chromatin and hypomethylation, with the former annotation predominant. At several loci (including CDC123, ADCY5, KLHDC5) the combination of fine-mapping genetic data and chromatin state enrichment maps, supplemented by allelic imbalance in chromatin accessibility pinpointed likely causal variants. The combination of increasingly-precise genetic and islet epigenomic information accelerates definition of causal mechanisms implicated in T2D pathogenesis.","abstract":"Human genetic studies have emphasised the dominant contribution of pancreatic islet dysfunction to development of Type 2 Diabetes (T2D). However, limited annotation of the islet epigenome has constrained efforts to define the molecular mechanisms mediating the, largely regulatory, signals revealed by Genome-Wide Association Studies (GWAS). We characterised patterns of chromatin accessibility (ATAC-seq, n=17) and DNA methylation (whole-genome bisulphite sequencing, n=10) in human islets, generating high-resolution chromatin state maps through integration with established ChIP-seq marks. We found enrichment of GWAS signals for T2D and fasting glucose was concentrated in subsets of islet enhancers characterised by open chromatin and hypomethylation, with the former annotation predominant. At several loci (including CDC123, ADCY5, KLHDC5) the combination of fine-mapping genetic data and chromatin state enrichment maps, supplemented by allelic imbalance in chromatin accessibility pinpointed likely causal variants. The combination of increasingly-precise genetic and islet epigenomic information accelerates definition of causal mechanisms implicated in T2D pathogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-25T23:19:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002593","title":"Illumina HiSeqX whole genome sequence data on 58 samples including 54 with known HTT triplet repeat expansions (2 premutation and 52 full expansions)","description":"Whole genome sequence (WGS) data was generated on 58 samples with validated repeat lengths for the CAG repeat associated with Huntington disease, These samples were sequenced using 2x150bp reads on an Illumina HiSeqX sequencer and the repeat expansions were called using ExpansionHunter to demonstrate the ability to call large repeats from high throughput, WGS data.","abstract":"Whole genome sequence (WGS) data was generated on 58 samples with validated repeat lengths for the CAG repeat associated with Huntington disease, These samples were sequenced using 2x150bp reads on an Illumina HiSeqX sequencer and the repeat expansions were called using ExpansionHunter to demonstrate the ability to call large repeats from high throughput, WGS data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-25T23:26:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002594","title":"The exomic landscape of t(14,18) negative diffuse follicular lymphoma with 1p36 deletion","description":"t(14,18) negative diffuse follicular lymphoma with 1p36 deletion is a well characterized variant of follicular lymphoma with typical clinical, morphological, immunophenotypical and genetic features. The genetic landscape of this variant is however largely unknown. We performed exome sequencing of six well characterised cases and detected  1642 single nucleotide variations and 641 insertions-deletions not reported in common databases (dbSNP and 1000G). We report several recurrent mutations, among which CREBBP, STAT6, KMT2D, HEATR6, LAMA5 and VPS13B are the most prevalent. Pathway annotation using GSEA showed an enrichment in mutated genes belonging to the MAPK pathway.","abstract":"t(14,18) negative diffuse follicular lymphoma with 1p36 deletion is a well characterized variant of follicular lymphoma with typical clinical, morphological, immunophenotypical and genetic features. The genetic landscape of this variant is however largely unknown. We performed exome sequencing of six well characterised cases and detected  1642 single nucleotide variations and 641 insertions-deletions not reported in common databases (dbSNP and 1000G). We report several recurrent mutations, among which CREBBP, STAT6, KMT2D, HEATR6, LAMA5 and VPS13B are the most prevalent. Pathway annotation using GSEA showed an enrichment in mutated genes belonging to the MAPK pathway.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-07-26T12:19:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002595","title":"Genome-wide Association Study of Sporadic CRC SG","description":"We performed a GWAS on 1,000 stringently defined cases and 1,000 age-, gender- and ethnicity-matched healthy controls using the SNP6 platform to identify risk loci for sporadic CRC in Singapore Chinese.","abstract":"We performed a GWAS on 1,000 stringently defined cases and 1,000 age-, gender- and ethnicity-matched healthy controls using the SNP6 platform to identify risk loci for sporadic CRC in Singapore Chinese.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002596","title":"SC_Mutation_call","description":"We are trying to develop a way of calling mutations from single cell RNA-sequencing data and are trying to do a control experiment where we single cell rna sequence a cell line for which the mutations are well characterised.","abstract":"We are trying to develop a way of calling mutations from single cell RNA-sequencing data and are trying to do a control experiment where we single cell rna sequence a cell line for which the mutations are well characterised.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002597","title":"Whole Genomes Define Concordance in Matched Primary, Xenograft, and Organoid Models of Pancreas Cancer","description":"Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of any common solid epithelial tumour. Multiple failed clinical trials necessitate newer approaches to understand the molecular etiology of this disease. Patient-derived xenografts (PDX) and patient-derived organoids (PDO) may serve as pre-clinical disease models; however, characterization remains largely unaddressed at the whole genome level. We conducted a comprehensive assessment of the genetic landscape of tumours and matched PDX and PDO from patients with PDAC. Our data show that PDX and PDO recapitulate PDAC tumourigenesis with respect to simple somatic mutations and copy number changes, and capture major structural variation events.","abstract":"Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of any common solid epithelial tumour. Multiple failed clinical trials necessitate newer approaches to understand the molecular etiology of this disease. Patient-derived xenografts (PDX) and patient-derived organoids (PDO) may serve as pre-clinical disease models; however, characterization remains largely unaddressed at the whole genome level. We conducted a comprehensive assessment of the genetic landscape of tumours and matched PDX and PDO from patients with PDAC. Our data show that PDX and PDO recapitulate PDAC tumourigenesis with respect to simple somatic mutations and copy number changes, and capture major structural variation events.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-01T19:34:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002598","title":"Illumina HiSeqX and HiSeq 2000 whole genome sequence data on 3,001 ALS samples including 212 with known C9orf72 repeat expansions","description":"Whole genome sequence (WGS) data was generated on 3,001 samples previously quantified for the presence of the C9orf72 repeat expansion (212 expanded and 2,789 wild type), These samples were sequenced using a combination of 2x100bp reads on an Illumina HiSeq2000 and 2x150bp reads on an Illumina HiSeqX sequencer. The repeat expansions were called using ExpansionHunter to demonstrate the ability to call large repeats from high throughput, WGS data. Provided here are all read pairs where at least one of the reads aligns within 1kb of the C9orf72 repeat expansion in addition to reads aligned in pre-determined off target locations where the aligners are known to mis-align reads.","abstract":"Whole genome sequence (WGS) data was generated on 3,001 samples previously quantified for the presence of the C9orf72 repeat expansion (212 expanded and 2,789 wild type), These samples were sequenced using a combination of 2x100bp reads on an Illumina HiSeq2000 and 2x150bp reads on an Illumina HiSeqX sequencer. The repeat expansions were called using ExpansionHunter to demonstrate the ability to call large repeats from high throughput, WGS data. Provided here are all read pairs where at least one of the reads aligns within 1kb of the C9orf72 repeat expansion in addition to reads aligned in pre-determined off target locations where the aligners are known to mis-align reads.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-01T21:59:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002599","title":"Chracterising_cellur_pathways_underlying_CD3_CD28_activation_of_human_CD4__cells","description":"We devised an approach to disentangle the TCR and CD28 pathways upon stimulation in naive and memory primary human CD4+ T cells (Tcons) in response to defined stimulatory signals. Isolated memory and naïve T cells were activated using anti-CD3, anti-CD28 or both in combination. As a control we cultured cells in the same conditions but without the stimuli. We carried Chipmentation using the H3K27ac antibody on 200,000 cross-linked cells. \n\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Two signals are necessary for a successful T cell activation; interaction of the T cell receptor (TCR) with the major histocompatibility complex II (MHC) antigens on the antigen presenting cells (APC) and interaction of the CD28 receptor on the lymphocyte with B7 proteins presented by the APC.  The role of CD28 receptor in T cell activation remains poorly understood, with an ongoing debate on whether it amplifies TCR based signal, drives unique changes in the cell or whether it is neede at all for certain T cell subsets activation. Self-recognition by TCR can lead to autoimmunity, highlighting the importance to better study these pathways using genomics tools.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-02T12:02:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002600","title":"Human_brain_Alzheimer_study_DNA","description":"This study includes single cell whole genome and transcriptom sequencing of single neuron cells (using G&amp;T method). Samples are from: normal human brains, patients with taupathies and Alzheimer disease.","abstract":"This study aimed to understand the role of somatic brain mosaicism in the pathogenesis of Tauopathies and Alzheimer disease. Additionally, it will explore the functional impact of acquired genetic variation in neurons of normal and diseased brain","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002601","title":"Human_brain_Alzheimer_study_RNA","description":"This study includes single cell whole genome and transcriptom sequencing of single neuron cells (using G&amp;T method). Samples are from: normal human brains, patients with taupathies and Alzheimer disease.","abstract":"This study aimed to understand the role of somatic brain mosaicism in the pathogenesis of Tauopathies and Alzheimer disease. Additionally, it will explore the functional impact of acquired genetic variation in neurons of normal and diseased brain","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002602","title":"H3Africa - An integrated approach to the identification of genetic determinants of susceptibility to trypanosomiasis","description":"The objective of the TrypanoGEN project is to discover genetic variants associated with different responses to sleeping sickness infection. The project was designed in two phases:Phase 1) Variant discovery; 222 samples were sequenced to approximately 10X coverage on an Illumina 2500 with 2x150bp reads, at the University of Liverpool Center for Genomic Research. In addition, 77 samples from Cameroon and Zambia were sequenced to approximately 30X Coverage at Baylor College of Medicine. The sequenced reads were mapped onto the 1000 genomes project human_g1k_v37_decoy reference genome using BWA. The SNP calling on all the samples was done using the genome analysis tool kit GATK v3.4. Samples were selected from seven populations where Trypanosomiasis is endemic: Nilo-Saharan speakers from North-West Uganda and Niger-Congo speakers from South-East Uganda, DRC, Ivory Coast, Guinea, Cameroon and Zambia. The samples included 182 controls,  97 cases, 17 latent infections and 3 suspect cases.  Phase 2) Variants discovered in Phase 1 will be used in the development of the H3Africa SNP chip. This chip will then be used in a GWAS study to identify variants associated with trypanosomiasis.","abstract":"The objective of the TrypanoGEN project is to discover genetic variants associated with different responses to sleeping sickness infection. The project was designed in two phases:Phase 1) Variant discovery; 222 samples were sequenced to approximately 10X coverage on an Illumina 2500 with 2x150bp reads, at the University of Liverpool Center for Genomic Research. In addition, 77 samples from Cameroon and Zambia were sequenced to approximately 30X Coverage at Baylor College of Medicine. The sequenced reads were mapped onto the 1000 genomes project human_g1k_v37_decoy reference genome using BWA. The SNP calling on all the samples was done using the genome analysis tool kit GATK v3.4. Samples were selected from seven populations where Trypanosomiasis is endemic: Nilo-Saharan speakers from North-West Uganda and Niger-Congo speakers from South-East Uganda, DRC, Ivory Coast, Guinea, Cameroon and Zambia. The samples included 182 controls,  97 cases, 17 latent infections and 3 suspect cases.  Phase 2) Variants discovered in Phase 1 will be used in the development of the H3Africa SNP chip. This chip will then be used in a GWAS study to identify variants associated with trypanosomiasis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-02T14:39:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002603","title":"Sequencing of liver dysplastic nodules and early hepatocellular carcinomas","description":"Pathologically premalignant lesions of HCCs have been designated as dysplastic nodules by the International Working Party.Genetic signatures of premalignant dysplastic nodules(DNs) with concurrent hepatocellular carcinoma(HCC) may provide an insight in the molecular evolution of hepatocellular carcinogenesis.here we analyzed four dysplastic nodules and four early hepatocellular carcinoma samples from the same patient with the \"nodule in nodule\" pattern.","abstract":"Pathologically premalignant lesions of HCCs have been designated as dysplastic nodules by the International Working Party.Genetic signatures of premalignant dysplastic nodules(DNs) with concurrent hepatocellular carcinoma(HCC) may provide an insight in the molecular evolution of hepatocellular carcinogenesis.here we analyzed four dysplastic nodules and four early hepatocellular carcinoma samples from the same patient with the \"nodule in nodule\" pattern.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002604","title":"Evolution and clinical impact of genetic epistasis within EGFR-mutant lung cancers","description":"The current understanding of tumorigenesis is largely centered on a monogenic driver oncogene model. This paradigm is incompatible with the prevailing clinical experience in most solid malignancies: monotherapy with a drug directed against an individual oncogenic driver typically results in incomplete clinical responses and eventual tumor progression1-7. By profiling the somatic genetic alterations present in over 2,000 cases of lung cancer, the leading cause of cancer mortality worldwide, we show that combinations of functional genetic alterations, i.e. genetic collectives dominate the landscape of advanced-stage disease. We highlight this polygenic landscape and evolution of advanced-stage non-small cell lung cancer (NSCLC) through the spatial-temporal genomic profiling of 7 distinct tumor biopsy specimens and 6 plasma specimens obtained from an EGFR-mutant NSCLC patient at (1) initial diagnosis of early-stage disease, (2) metastatic progression, (3) sequential treatment and resistance to 2 EGFR inhibitors, (4) death. The comprehensive genomic analysis of this case, coupled with circulating free (cf) tumor DNA profiling of additional advanced-stage EGFR-mutant NSCLC clinical cohorts with associated treatment responses uncovered features of evolutionary selection for multiple concurrent gene alterations: including the presence of EGFR inhibitor-sensitive (EGFRL858R;EGFRexon19del) or inhibitor-resistant (EGFRT790M;EGFRC797S) forms of oncogenic EGFR along with cell cycle gene alterations (e.g. in CDK4/6, CCNE1, RB1) and activating alterations in WNT/β-catenin and PI3K pathway genes, which our data suggest can cooperatively impart non-redundant functions to limit EGFR targeted therapy response and/or promote tumor progression. Moreover, evidence of an unanticipated parallel evolution of both EGFR T790M and two distinct forms of oncogenic PIK3CA was observed. Our study provides a large-scale clinical and genetic dataset of advanced-stage EGFR-mutant NSCLC, a rationale for specific polytherapy strategies such as EGFR and CDK4/6 inhibitor co-treatment to potentially enhance clinical outcomes, and prompts a re-evaluation of the prevailing paradigm of monogenic-based molecular stratification for targeted therapy. Instead, our findings highlight an alternative model of genetic collectives that operate through epistasis to drive lung cancer progression and therapy resistance.","abstract":"The current understanding of tumorigenesis is largely centered on a monogenic driver oncogene model. This paradigm is incompatible with the prevailing clinical experience in most solid malignancies: monotherapy with a drug directed against an individual oncogenic driver typically results in incomplete clinical responses and eventual tumor progression1-7. By profiling the somatic genetic alterations present in over 2,000 cases of lung cancer, the leading cause of cancer mortality worldwide, we show that combinations of functional genetic alterations, i.e. genetic collectives dominate the landscape of advanced-stage disease. We highlight this polygenic landscape and evolution of advanced-stage non-small cell lung cancer (NSCLC) through the spatial-temporal genomic profiling of 7 distinct tumor biopsy specimens and 6 plasma specimens obtained from an EGFR-mutant NSCLC patient at (1) initial diagnosis of early-stage disease, (2) metastatic progression, (3) sequential treatment and resistance to 2 EGFR inhibitors, (4) death. The comprehensive genomic analysis of this case, coupled with circulating free (cf) tumor DNA profiling of additional advanced-stage EGFR-mutant NSCLC clinical cohorts with associated treatment responses uncovered features of evolutionary selection for multiple concurrent gene alterations: including the presence of EGFR inhibitor-sensitive (EGFRL858R;EGFRexon19del) or inhibitor-resistant (EGFRT790M;EGFRC797S) forms of oncogenic EGFR along with cell cycle gene alterations (e.g. in CDK4/6, CCNE1, RB1) and activating alterations in WNT/β-catenin and PI3K pathway genes, which our data suggest can cooperatively impart non-redundant functions to limit EGFR targeted therapy response and/or promote tumor progression. Moreover, evidence of an unanticipated parallel evolution of both EGFR T790M and two distinct forms of oncogenic PIK3CA was observed. Our study provides a large-scale clinical and genetic dataset of advanced-stage EGFR-mutant NSCLC, a rationale for specific polytherapy strategies such as EGFR and CDK4/6 inhibitor co-treatment to potentially enhance clinical outcomes, and prompts a re-evaluation of the prevailing paradigm of monogenic-based molecular stratification for targeted therapy. Instead, our findings highlight an alternative model of genetic collectives that operate through epistasis to drive lung cancer progression and therapy resistance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-03T10:03:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002605","title":"The chromatin accessibility signature of human immune aging stems from CD8+ T cells","description":"Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel the regulatory programsbehind these changes, we applied systems immunology approaches and profiled chromatin accessibility and the transcriptomein PBMCs, purified monocytes, and B and T cells. Analysis of samples from 77 young and elderly donors revealed a novel androbust aging signature in PBMCs, with simultaneous systematic chromatin closing at promoters and enhancers associated withT cell signaling and a potentially stochastic chromatin opening mostly found at quiescent and repressed sites. Combined analysesof chromatin accessibility and the transcriptome uncovered immune molecules activated/inactivated with aging andidentified the silencing of the IL7R gene and the IL-7 signaling pathway genes as potential biomarkers. This signature is borneby memory CD8+ T cells, which exhibited an aging-related loss in binding of NF-κB and STAT factors. Thus, our study providesa unique and comprehensive approach to identifying candidate biomarkers and provides mechanistic insights into aging-associatedimmunodeficiency.","abstract":"Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel the regulatory programsbehind these changes, we applied systems immunology approaches and profiled chromatin accessibility and the transcriptomein PBMCs, purified monocytes, and B and T cells. Analysis of samples from 77 young and elderly donors revealed a novel androbust aging signature in PBMCs, with simultaneous systematic chromatin closing at promoters and enhancers associated withT cell signaling and a potentially stochastic chromatin opening mostly found at quiescent and repressed sites. Combined analysesof chromatin accessibility and the transcriptome uncovered immune molecules activated/inactivated with aging andidentified the silencing of the IL7R gene and the IL-7 signaling pathway genes as potential biomarkers. This signature is borneby memory CD8+ T cells, which exhibited an aging-related loss in binding of NF-κB and STAT factors. Thus, our study providesa unique and comprehensive approach to identifying candidate biomarkers and provides mechanistic insights into aging-associatedimmunodeficiency.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-03T13:51:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002606","title":"Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma","description":"Diffuse large B cell lymphoma (DLBCL) is the most common hematologic malignancy and is characterized by a striking degree of heterogeneity. We enrolled a total of 1001 DLBCL patients and comprehensively defined the landscape of genetic mutations, copy number alterations and expression through whole-exome and transcriptome sequencing. We identified 150 genetic drivers of DLBCL including many novel, clinically relevant genes (e.g. SPEN, SETD1B and KLHL14). Genetic drivers were highly enriched among essential genes identified by CRISPR screening in DLBCL cell lines including those of immediate potential therapeutic relevance such as MTOR, SYK, SF3B1 and XPO1. RHOA emerged as a critical driver gene from our genetic analysis and CRISPR screen; we further delineated its functional role in vitro and in vivo models to define its role as an essential oncogene in DLBCL. Our work thus identifies the functional landscape of genetic drivers and their clinical and therapeutic relevance in DLBCL patients.","abstract":"Diffuse large B cell lymphoma (DLBCL) is the most common hematologic malignancy and is characterized by a striking degree of heterogeneity. We enrolled a total of 1001 DLBCL patients and comprehensively defined the landscape of genetic mutations, copy number alterations and expression through whole-exome and transcriptome sequencing. We identified 150 genetic drivers of DLBCL including many novel, clinically relevant genes (e.g. SPEN, SETD1B and KLHL14). Genetic drivers were highly enriched among essential genes identified by CRISPR screening in DLBCL cell lines including those of immediate potential therapeutic relevance such as MTOR, SYK, SF3B1 and XPO1. RHOA emerged as a critical driver gene from our genetic analysis and CRISPR screen; we further delineated its functional role in vitro and in vivo models to define its role as an essential oncogene in DLBCL. Our work thus identifies the functional landscape of genetic drivers and their clinical and therapeutic relevance in DLBCL patients.","study_type":"Other","pubmed_ids":[28985567],"external_links":null,"is_released":true,"released_date":"2017-08-03T19:40:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002607","title":"Comparative genomics research for Chinese colorectal cancer","description":"In order to clarify the mechanisms of genesis and development of colorectal carcinoma, in this study, we performed comparative genomics research in Chinese colorectal cancer at various clinical stage via whole exon sequencing or whole genome sequencing. Comparative bioinformatical analysis was perform to find the difference on somatic single-nucleotide variants, short insert/deletion variants, genomic structural variants, and copy number variants between cancer tissue and normal tissue, or among cancer tissues at various clinical stages.","abstract":"In order to clarify the mechanisms of genesis and development of colorectal carcinoma, in this study, we performed comparative genomics research in Chinese colorectal cancer at various clinical stage via whole exon sequencing or whole genome sequencing. Comparative bioinformatical analysis was perform to find the difference on somatic single-nucleotide variants, short insert/deletion variants, genomic structural variants, and copy number variants between cancer tissue and normal tissue, or among cancer tissues at various clinical stages.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-07T06:51:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002608","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__clear_cell_renal_cell_carcinoma","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute (Illumina HiSeqX, 40X and 20X depth respectively). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \n\nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-07T15:50:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002609","title":"Reduced Representation Bisulfite Sequencing (RRBS) in various tissues to discover DNA methylation markers for the diagnosis of breast and ovarian cancer.","description":"Despite a myriad of attempts in the last three decades to diagnose ovarian cancer (OC) earlier, this clinical aim still remains a significant challenge. In addition, monitoring treatment and early detection of fatal breast cancer (BC) remains a major unmet need. Aberrant methylation patterns of linked CpGs analyzed in DNA fragments shed by cancers into the bloodstream (i.e. cell-free DNA) can provide highly specific signals indicating cancer presence.In order to discover the most relevant CpG regions, we used RRBS and analysed several tissue samples: 11 prospectively collected invasive epithelial ovarian cancer samples (high grade serous n=8, low grade serous n=1, endometrioid n=1, mucinous n=1, mean age = 54.7 years), 8 prospectively collected invasive ductal breast cancer samples (2/8 triple negative; mean age = 56.6 years), one benign tumor (papillary serous cystadenoma, age = 86 years), 18 non-neoplastic tissue samples (breast n=7 and adnexal n=11, mean age = 60.2 years), two non-neoplastic endometrial tissues (mean age = 68 years) and twenty three white blood cell samples (mean age = 57.8 years) were assessed by RRBS. Genome wide methylation analysis was performed by Reduced Representation Bisulfite Sequencing (RRBS) at GATC Biotech. DNA was digested with MspI followed by size selection of the library, providing enhanced coverage for the CpG-rich regions. The digested DNA was adapter ligated, bisulfite modified and PCR amplified. The libraries were sequenced on Illumina’s HiSeq 2500. Analysis of the first samples sequenced with 100bp paired-end mode showed that the library insert size was small. Therefore, the remaining samples were sequenced with 50 bp paired-end mode. Using Genedata Expressionist® for Genomic Profiling v9.1, we established a bioinformatics pipeline for the detection of cancer specific differentially methylated regions (DMRs). The most promising DMRs were taken forward for the development and validation of serum based clinical assays.","abstract":"Despite a myriad of attempts in the last three decades to diagnose ovarian cancer (OC) earlier, this clinical aim still remains a significant challenge. In addition, monitoring treatment and early detection of fatal breast cancer (BC) remains a major unmet need. Aberrant methylation patterns of linked CpGs analyzed in DNA fragments shed by cancers into the bloodstream (i.e. cell-free DNA) can provide highly specific signals indicating cancer presence.In order to discover the most relevant CpG regions, we used RRBS and analysed several tissue samples: 11 prospectively collected invasive epithelial ovarian cancer samples (high grade serous n=8, low grade serous n=1, endometrioid n=1, mucinous n=1, mean age = 54.7 years), 8 prospectively collected invasive ductal breast cancer samples (2/8 triple negative; mean age = 56.6 years), one benign tumor (papillary serous cystadenoma, age = 86 years), 18 non-neoplastic tissue samples (breast n=7 and adnexal n=11, mean age = 60.2 years), two non-neoplastic endometrial tissues (mean age = 68 years) and twenty three white blood cell samples (mean age = 57.8 years) were assessed by RRBS. Genome wide methylation analysis was performed by Reduced Representation Bisulfite Sequencing (RRBS) at GATC Biotech. DNA was digested with MspI followed by size selection of the library, providing enhanced coverage for the CpG-rich regions. The digested DNA was adapter ligated, bisulfite modified and PCR amplified. The libraries were sequenced on Illumina’s HiSeq 2500. Analysis of the first samples sequenced with 100bp paired-end mode showed that the library insert size was small. Therefore, the remaining samples were sequenced with 50 bp paired-end mode. Using Genedata Expressionist® for Genomic Profiling v9.1, we established a bioinformatics pipeline for the detection of cancer specific differentially methylated regions (DMRs). The most promising DMRs were taken forward for the development and validation of serum based clinical assays.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-08T14:17:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002610","title":"Somatic_Variation_Angiosarcoma","description":"Through whole genome sequencing, this study will explore the mutational profiles and signatures within an angiosarcoma tumour from a patient with xeroderma pimentosum. Very little information is known about this tumour type and it has not previously been studied within the context of xerogerma pigmentosum.","abstract":"Through whole genome sequencing, this study will explore the mutational profiles and signatures within an angiosarcoma tumour from a patient with xeroderma pimentosum. Very little information is known about this tumour type and it has not previously been studied within the context of xerogerma pigmentosum.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-09T09:44:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002611","title":"Identification_and_functional_characterization_of_secondary_iTreg_clones_in_tumor_patients","description":"Regulatory T-cells (Treg) are a major obstacle of efficient cancer immune-surveillance, as they prevent tumor eradication by tumor-antigen (TA)-specific conventional T cells (Tconv), supporting cancer development.  Indeed, Treg numbers are increased in tumors and peripheral blood of cancer patients correlating with poor prognosis. Thus, understanding the mechanisms of Treg repertoire formation in cancer patients is of major importance for the design of efficient cancer immunotherapies. In tumor-bearing mice, Treg accumulation results predominantly from the proliferation of pre-existing natural Treg (nTreg) but also from the conversion of tumor-killing Tconv into tumor-promoting induced Treg (iTreg) under suppressive conditions within the tumor-microenvironment. Nevertheless, Treg origin in tumor patients remains largely unknown. This study investigates the existence of TA-specific iTreg in tumor patients and their relevant contribution to the TCR repertoire of the Treg pool in the periphery.  A few highly-expanded clonotypes were detected among both Treg and Tconv from cancer patients in contrast to the highly polyclonal populations in healthy individuals. However, no major overlap was observed between Treg and Tconv in the blood of tumor patients and healthy individuals, arguing against the existence of tumor-specific iTreg in the circulation. Interestingly, within tumors of the same patients we detected highly expanded clones not only among Treg but also within an intermediate Activated (Act Tconv) population. Both Tconv and Act Tconv subsets shared dominant highly expanded clonotypes with Treg, shaping of the tumor-infiltrating Treg repertoire but with no effect in Treg from peripheral blood. Taken together, our data support the hypothesis that within the tumor dominant tumor-killing TA-specific Tconv may convert to tumor-promoting iTreg with a major impact on the tumor-infiltrating Treg population. To prove this hypothesis, we need to identify whether two different cells, one of a Treg suppressive profile and one of a non-suppressive tumor-killing Tconv phenotype, share the same TCR and, thus, have a common clonal origin due to peripheral iTreg generation. To this direction, we have already isolated tumor-infiltrating Treg and Tconv from freshly resected tumors and blood of breast cancer patients using single-cell FACS sorting and plan to apply the G&amp;T method that combines total mRNA sequencing  and methylation analysis on the same single-cell, as already established by the group of Prof. Thierry Voet (Macaulay et al 2015).\n\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"To prove our hypothesis, we need to identify whether two different cells, one of a Treg suppressive profile and one of a non-suppressive tumor-killing Tconv phenotype, share the same TCR and, thus, have a common clonal origin due to peripheral iTreg generation. To this direction, we have already isolated tumor-infiltrating Treg and Tconv from freshly resected tumors and blood of breast cancer patients using single-cell FACS sorting and plan to apply the G&amp;T method that combines total mRNA sequencing  and methylation analysis on the same single-cell, as already established by the group of Prof. Thierry Voet (Macaulay et al 2015).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002612","title":"The genomic landscape of cutaneous squamous cell carcinoma from immunosuppressed and immunocompetent patients reveals common drivers and a novel mutational signature associated with chronic azathioprine exposure","description":"Cutaneous squamous cell carcinoma (cSCC) has a high tumour mutational burden (50 mutations per megabase DNA pair). Combining whole exome analyses from 40 primary cSCC tumours, comprising 20 well differentiated and 20 moderately/poorly differentiated tumours, with accompanying clinical data from a longitudinal study of immunosuppressed and immunocompetent patients, coupled with integration of independent gene expression studies has allowed the identification of commonly mutated genes and altered pathways and processes. Mutational signature analysis revealed the presence of a novel signature (signature 32), which was found exclusively in the tumours from immunosuppressed patients who had been exposed to azathioprine. Characterisation of a panel of 15 keratinocyte cancer cell lines derived from tumours from immunocompetent and immunosuppressed patients reveals that they accurately reflect the mutational signatures and genomic alterations of primary tumours and provide a resource for the validation of tumour drivers and therapeutic targets.","abstract":"Cutaneous squamous cell carcinoma (cSCC) has a high tumour mutational burden (50 mutations per megabase DNA pair). Combining whole exome analyses from 40 primary cSCC tumours, comprising 20 well differentiated and 20 moderately/poorly differentiated tumours, with accompanying clinical data from a longitudinal study of immunosuppressed and immunocompetent patients, coupled with integration of independent gene expression studies has allowed the identification of commonly mutated genes and altered pathways and processes. Mutational signature analysis revealed the presence of a novel signature (signature 32), which was found exclusively in the tumours from immunosuppressed patients who had been exposed to azathioprine. Characterisation of a panel of 15 keratinocyte cancer cell lines derived from tumours from immunocompetent and immunosuppressed patients reveals that they accurately reflect the mutational signatures and genomic alterations of primary tumours and provide a resource for the validation of tumour drivers and therapeutic targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-09T15:51:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002613","title":"FCA","description":"We are doing single-cell RNAseq from adult skin to study new cell populations and their functions.\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"This project aims to deconstruct the human skin to its individual cellular constituents using single cell technologies. In this pursuit, we will define the cell census and functional niches within the human skin","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002614","title":"Capture Hi-C on MM","description":"In situ promoter capture Hi-C on multiple myeloma cell line KMS11 in experimental triplicates. Hi-C libraries were prepared as previously described (Rao et al., 2014, http://dx.doi.org/10.1016/j.cell.2014.11.021). Promoter capture was based on 32,313 biotinylated 120-mer RNA baits (Agilent). Hi-C libraries were sequenced using Illumina HiSeq 2000 technology. The files are in FASTQ format.","abstract":"In situ promoter capture Hi-C on multiple myeloma cell line KMS11 in experimental triplicates. Hi-C libraries were prepared as previously described (Rao et al., 2014, http://dx.doi.org/10.1016/j.cell.2014.11.021). Promoter capture was based on 32,313 biotinylated 120-mer RNA baits (Agilent). Hi-C libraries were sequenced using Illumina HiSeq 2000 technology. The files are in FASTQ format.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-11T17:29:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002615","title":"A transgenerational MMACHC epimutation illustrates a new mechanism for inborn errors of metabolism","description":"Up to now, the epimutations reported in man have been somatic, without germlinetransmission. We report the transgenerational transmission of a constitutional epimutation inthe cblC class of inborn error of vitamin B12 metabolism that we named epi-cblC. Subjectscarry, in trans, a heterozygous MMACHC mutation and a promoter epimutation, detectable inblood, fibroblasts and sperm; the epimutation was transmitted through three generations. 5-Azacytidine restored the MMACHC expression in fibroblasts. MMACHC is flanked byCCDC163P and PRDX1, which are in the opposite orientation. Genome-wide sequencingidentified PRDX1 mutations that forced antisense transcription of MMACHC, resulting in aH3K36me3 mark in the promoter. The silencing of PRDX1 transcription produced a partialhypomethylation of the epiallele and restored the expression of MMCHC. The example of epicblC shows the need to look for compound epigenetic/genetic heterozygosity in patients with typical disease manifestation and genetic heterozygosity in disease-causing genes located in other gene trios.","abstract":"Up to now, the epimutations reported in man have been somatic, without germlinetransmission. We report the transgenerational transmission of a constitutional epimutation inthe cblC class of inborn error of vitamin B12 metabolism that we named epi-cblC. Subjectscarry, in trans, a heterozygous MMACHC mutation and a promoter epimutation, detectable inblood, fibroblasts and sperm; the epimutation was transmitted through three generations. 5-Azacytidine restored the MMACHC expression in fibroblasts. MMACHC is flanked byCCDC163P and PRDX1, which are in the opposite orientation. Genome-wide sequencingidentified PRDX1 mutations that forced antisense transcription of MMACHC, resulting in aH3K36me3 mark in the promoter. The silencing of PRDX1 transcription produced a partialhypomethylation of the epiallele and restored the expression of MMCHC. The example of epicblC shows the need to look for compound epigenetic/genetic heterozygosity in patients with typical disease manifestation and genetic heterozygosity in disease-causing genes located in other gene trios.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002616","title":"Breast cancer women lack normal lifelong immune response after full-term pregnancies","description":"Immunological tolerance during pregnancy is necessary for women’s bodies to accept the semi-allogenic fetus. Interestingly, “immune evasion”, which consists of some similar immunological changes, was recently proposed as a hallmark of cancer. Looking at these results, it seems paradoxical that increasing number of full-term pregnancies (FTP) reduces the risk of breast cancer in women. Our aim was to use a systems epidemiology approach to investigate this paradox by modelling breast cancer incidence as a function of parity in the Norwegian Women and Cancer (NOWAC) cohort, then testing the mathematical model using gene expression from blood in a subcohort of these women: the NOWAC postgenome cohort. Lastly, we undertook a gene set enrichment analysis for immunological gene sets. A linear trend nicely fitted the dataset showing an 8% decrease in risk for each FTP, independent of stratification on other risk factors and lasting for decades after a woman’s last FTP. However, when we looked at gene expression we found that hundreds of genes showed linear trends in cancer-free controls, but this was not the case in /any/ of the samples from breast cancer cases. In the gene set enrichment analysis, samples consisted of human blood or cord blood and mouse bone marrow or spleen. We found more adaptive gene sets than expected in humans and more innate gene sets than expected in mice. None of the gene sets provided information about the long-term effects of immunological tolerance during pregnancy, but the lack of relevant reductionist experiments hampers our interpretation. We suggest that, after resolution at birth, the immunological tolerance induced by pregnancy augments immune response to cancer development.","abstract":"Immunological tolerance during pregnancy is necessary for women’s bodies to accept the semi-allogenic fetus. Interestingly, “immune evasion”, which consists of some similar immunological changes, was recently proposed as a hallmark of cancer. Looking at these results, it seems paradoxical that increasing number of full-term pregnancies (FTP) reduces the risk of breast cancer in women. Our aim was to use a systems epidemiology approach to investigate this paradox by modelling breast cancer incidence as a function of parity in the Norwegian Women and Cancer (NOWAC) cohort, then testing the mathematical model using gene expression from blood in a subcohort of these women: the NOWAC postgenome cohort. Lastly, we undertook a gene set enrichment analysis for immunological gene sets. A linear trend nicely fitted the dataset showing an 8% decrease in risk for each FTP, independent of stratification on other risk factors and lasting for decades after a woman’s last FTP. However, when we looked at gene expression we found that hundreds of genes showed linear trends in cancer-free controls, but this was not the case in /any/ of the samples from breast cancer cases. In the gene set enrichment analysis, samples consisted of human blood or cord blood and mouse bone marrow or spleen. We found more adaptive gene sets than expected in humans and more innate gene sets than expected in mice. None of the gene sets provided information about the long-term effects of immunological tolerance during pregnancy, but the lack of relevant reductionist experiments hampers our interpretation. We suggest that, after resolution at birth, the immunological tolerance induced by pregnancy augments immune response to cancer development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-14T10:04:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002617","title":"AngioPredict CNV and Exome data","description":"AngioPredict CNV and Exome data","abstract":"AngioPredict CNV and Exome data","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-14T10:14:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002618","title":"Clonal expansion and epigenetic reprogramming following deletion or amplification of mutant IDH","description":"Initially IDH1 mutant gliomas are shown to have IDH1 is deletions or amplifications at recurrence yielding a higher-grade tumor with a reprogrammed epigenome. We also report systematic selection for cells with IDH1 CNA in vitro and in vivo.","abstract":"Initially IDH1 mutant gliomas are shown to have IDH1 is deletions or amplifications at recurrence yielding a higher-grade tumor with a reprogrammed epigenome. We also report systematic selection for cells with IDH1 CNA in vitro and in vivo.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-14T21:20:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002619","title":"Cryptic Relatedness in the Singapore Living Biobank Project","description":"The Singapore Living Biobank is a collection of healthy population-based Chinese and Malay individuals, for the purpose of phenotype recall study of high-impact variant carriers. These individuals are sampled from two studies: Multi-Ethnic Cohort (MEC), and the Singapore Health 2012 (SH2012). The MEC is a population-based cohort initiated in 2007 to investigate the genetic and lifestyle factors that affect the risk of developing chronic diseases such as diabetes and cardiovascular outcomes in the three ethnic groups (Chinese, Malays, and Indians). The SH2012 study is a population-based cross-sectional survey conducted in Singapore between 2012 and 2013, with over-sampling of Malays and Indians. Participants in MEC and SH2012 completed a similar set of questionnaire components, health examination, and biochemisty panels. Description of the MEC and SH2012 studies can be found at http://blog.nus.edu.sg/sphs/. We generated whole-exome sequencing data and Illumina OmniExpress array genotyping data for 1,299 Chinese and 1,229 Malays from the Singapore Living Biobank. This study includes a subset of 762 individuals that were found to be closely related (≤3rd degree), including 263 Chinese and 499 Malays.","abstract":"The Singapore Living Biobank is a collection of healthy population-based Chinese and Malay individuals, for the purpose of phenotype recall study of high-impact variant carriers. These individuals are sampled from two studies: Multi-Ethnic Cohort (MEC), and the Singapore Health 2012 (SH2012). The MEC is a population-based cohort initiated in 2007 to investigate the genetic and lifestyle factors that affect the risk of developing chronic diseases such as diabetes and cardiovascular outcomes in the three ethnic groups (Chinese, Malays, and Indians). The SH2012 study is a population-based cross-sectional survey conducted in Singapore between 2012 and 2013, with over-sampling of Malays and Indians. Participants in MEC and SH2012 completed a similar set of questionnaire components, health examination, and biochemisty panels. Description of the MEC and SH2012 studies can be found at http://blog.nus.edu.sg/sphs/. We generated whole-exome sequencing data and Illumina OmniExpress array genotyping data for 1,299 Chinese and 1,229 Malays from the Singapore Living Biobank. This study includes a subset of 762 individuals that were found to be closely related (≤3rd degree), including 263 Chinese and 499 Malays.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-15T06:14:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002620","title":"YFV_specific_CD8_T_cells","description":"We are interesting in understanding the effect of Yellow Fever Vaccination on antigen-specific CD8 T cell responses in peripheral blood of human volunteers. This study is the initial pilot to check whether prior freezing of the cells is compatible with single-cell RNAseq processing and subsequent analysis with TRaCeR to determine TCR sequencing from the transcriptome.","abstract":"We previously showed that the YF-17D vaccine induces a stem cell-like memory (SCM) CD8 T cell subset (Fuertes Marraco et al. Sci. Trans. Med. 2015). We could detect YFV-specific CD8 T cells in N=38/41 vaccinees with a vaccination history ranging from a few months to 35 years. In contrast to the effector CD8 T cells that decline with increasing years since vaccination, the YFV-specific CD8 SCM are stable and last for decades.\nIn this new study, we aim to analyze the longitudinal dynamics of YFV-specific CD8 T cells following vaccination. We recruited healthy volunteers and obtained samples at baseline and several time-points after vaccination with YF-17D. In order to maximally comprehend the complexity of the CD8 T cell response, we plan to analyze YFV-specific CD8 T cell subsets using the T cell-dedicated single cell RNA sequencing technology from TraCeR (Stubbington et al Nature Methods 2016). This technology allows to reconstruct and assemble TCRs in combination with transcriptome information at the single cell level.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002621","title":"Multi-omics Profiling of Asian Breast Cancers","description":"Whole exome and transcriptome sequencing data of primary tumors from 178 Korean breast cancer patients.","abstract":"Whole exome and transcriptome sequencing data of primary tumors from 178 Korean breast cancer patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-16T08:05:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002622","title":"Sensitive Monogenic Noninvasive Prenatal Diagnosis by Targeted Haplotyping","description":"During pregnancy, cell-free DNA (cfDNA) in maternal blood encompasses a small percentage of cell-free fetal DNA (cffDNA), an easilyaccessible source for determination of fetal disease status in risk families through non-invasive procedures. In case of monogenic heritabledisease, background maternal cfDNA prohibits direct observation of the maternally inherited allele. Non-invasive prenatal diagnostics(NIPD) of monogenic diseases therefore relies on parental haplotyping and statistical assessment of inherited alleles from cffDNA,techniques currently unavailable for routine clinical practice. Here, we present monogenic NIPD (MG-NIPD), which requires a bloodsample from both parents, for targeted locus amplification (TLA)-based phasing of heterozygous variants selectively at a gene of interest.Capture probes-based targeted sequencing of cfDNA from the pregnant mother and a tailored statistical analysis enables predicting fetalgene inheritance. MG-NIPD was validated for 18 pregnancies, focusing on CFTR, CYP21A2, and HBB. In all cases we could predict theinherited alleles with &gt;98% confidence, even at relatively early stages (8 weeks) of pregnancy. This prediction and the accuracy ofparental haplotyping was confirmed by sequencing of fetal material obtained by parallel invasive procedures. MG-NIPD is a robustmethod that requires standard instrumentation and can be implemented in any clinic to provide families carrying a severe monogenicdisease with a prenatal diagnostic test based on a simple blood draw.","abstract":"During pregnancy, cell-free DNA (cfDNA) in maternal blood encompasses a small percentage of cell-free fetal DNA (cffDNA), an easilyaccessible source for determination of fetal disease status in risk families through non-invasive procedures. In case of monogenic heritabledisease, background maternal cfDNA prohibits direct observation of the maternally inherited allele. Non-invasive prenatal diagnostics(NIPD) of monogenic diseases therefore relies on parental haplotyping and statistical assessment of inherited alleles from cffDNA,techniques currently unavailable for routine clinical practice. Here, we present monogenic NIPD (MG-NIPD), which requires a bloodsample from both parents, for targeted locus amplification (TLA)-based phasing of heterozygous variants selectively at a gene of interest.Capture probes-based targeted sequencing of cfDNA from the pregnant mother and a tailored statistical analysis enables predicting fetalgene inheritance. MG-NIPD was validated for 18 pregnancies, focusing on CFTR, CYP21A2, and HBB. In all cases we could predict theinherited alleles with &gt;98% confidence, even at relatively early stages (8 weeks) of pregnancy. This prediction and the accuracy ofparental haplotyping was confirmed by sequencing of fetal material obtained by parallel invasive procedures. MG-NIPD is a robustmethod that requires standard instrumentation and can be implemented in any clinic to provide families carrying a severe monogenicdisease with a prenatal diagnostic test based on a simple blood draw.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-16T13:02:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002623","title":"Single_cell_RNA_seq_of_human_primary_gut_epithelial_cells","description":"Single cell RNA-seq characterisation of  the human fetal gut epithelial  populations\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"The use of foetal tissue from elective termination of pregnancies offers a number of unique research opportunities. This includes:\n•\tGrowing cells from the developing foetus to better understand how these cells give rise to the organ they are forming. In addition, this work also generates a possible source of cells for implantation to replace those lost in adults with disease involving these same systems. For example, the isolation of cells from a part of the brain called the striatum has been used in a clinical transplant study in adults with mild-moderate Huntington’s Disease, where the striatum is known to be heavily affected by the disease process ;\n•\tGrowing and enriching for stem cells from the developing foetus, this can then be expanded in vitro. These cells can be used also as a source for grafting into patients with diseases of the relevant systems. For example, growing stem cells from the foetal brain and then engineering them to turn into the dopaminergic nerve cells that are lost in Parkinson’s disease (PD);\n•\tHistological studies to better capture and define the normal development of a specific organ or region of brain. This is often done to corroborate and better understand what has been described in other mammalian systems, given the longer developmental times for human organ systems. An example would be in better understanding the expression of relevant factors in the developing human midbrain, so that we can better understand how dopamine neurons normally develop and by so doing better manipulate the stem cells to this fate.\nThus, this project is designed for this work to be done using different elements of the foetal material and includes many different regions including the brain, skin, liver and thymus for example.\n\nThe work with human foetal tissue therefore involves:\n•\tIn vitro culturing of the tissue and the generation of cell lines in some instances;\n•\tIn vivo grafting of some of the tissue and its derivatives into animal models of disease;\n•\tIn vivo grafting of the tissue in some instances into patients with neurological disease in early phase I clinical trials looking at cell replacement;\n•\tFixing bits of the developing foetus for histological studies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002624","title":"The_genetics_of_thinness_compared_to_obesity","description":"The variation in weight within a shared environment is largely attributable to genetic factors. Whilst many genes/loci confer susceptibility to obesity, little is known about the genetic architecture of thinness. In this study we performed a genome-wide association study of 1,622 persistently thin healthy individuals (STILTS), 1,985 severe childhood onset obesity cases (SCOOP) and 10,433 population based individuals (UKHLS) used as a common set of controls. All participants were genotyped on the Illumina Core Exome array, including 551,839 markers and imputed to the combined UK10K and 1000G (phase3) reference panel. We contrast the genetic architecture of thinness with that of severe early onset obesity and explore whether the genetic loci influencing thinness are the same as those influencing obesity pr whether there  are important genetic differences between them.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing","abstract":"The variation in weight within a shared environment is largely attributable to genetic factors. Whilst many genes/loci confer susceptibility to obesity, little is known about the genetic architecture of thinness. In this study we performed a genome-wide association study of 1,622 persistently thin healthy individuals (STILTS), 1,985 severe childhood onset obesity cases (SCOOP) and 10,433 population based individuals (UKHLS) used as a common set of controls. All participants were genotyped on the Illumina Core Exome array, including 551,839 markers and imputed to the combined UK10K and 1000G (phase3) reference panel. The UKHLS data is available for download from the EGA with accession code EGAS00001001232.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-18T14:45:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002625","title":"Clonal evolution study of Intrahepatic cholangiocarcinoma in Zhongshan Hospital","description":"Clonal evolution study of Intrahepatic cholangiocarcinoma","abstract":"Clonal evolution study of Intrahepatic cholangiocarcinoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-20T13:13:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002626","title":"Somatic_mutation_and_clonal_evolution_in_the_human_pancreas___WGS","description":"In this study we aim to characterise the landscape of mutation and clonal selection in the human pancreas. The study combines targeted sequencing and whole-genome sequencing of microbiopsies from the pancreas. The range of patients studied will include healthy individuals, both smokers and non-smokers, and patients with pancreatic ductal adenocarcinoma.","abstract":"In this study we aim to characterise the landscape of mutation and clonal selection in the human pancreas. The study combines targeted sequencing and whole-genome sequencing of microbiopsies from the pancreas. The range of patients studied will include healthy individuals, both smokers and non-smokers, and patients with pancreatic ductal adenocarcinoma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-22T12:26:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002627","title":"Ultra-Fast Patient-Derived Xenografts Identify Functional and Spatial Tumour Heterogeneities that Drive Therapeutic Resistance","description":"Treatment of patients with advanced cancers increasingly relies on agents targeting specific molecular or cellular aberrations. These expensive therapies often fail because of pre-existing drug resistance. Intra-tumoural molecular and micro-environmental heterogeneity resistance can create resistance in one or more subclones of a tumour, leading to spatio-functional heterogeneity. We created a rapid approach for quantifying tumour functional phenotypes based on tumour-implantation into the chorioallantoic membrane of chick embryos. We apply this technique to 43 separate biopsies from 6 patients with renal cell carcinoma (RCC) with 36 replicates per biopsy, achieving a 93.6% engraftment rate (1449/1548). Challenging these models with sunitinib, an anti-angiogenic therapy frequently used in RCC allowed us to quantify spatio-functional heterogeneity in individual patients. Prediction of de novo drug resistance in advanced cancer patients would facilitate precision medicine by tailoring systemic therapies and improve clinical trial design outcome measures. We describe a patient-derived xenograft platform where fresh patient tumour samples are implanted into the chorioallantoic membrane (CAM) of chick embryos at high engraftment efficiencies, permitting large scale “tumour avatar” studies to guide the selection of drugs and to predict clinical drug resistance outcomes in renal cell carcinoma (RCC) patients. Applying this “tumour avatar” model in a co-clinical trial on RCC patients, we observe intra-tumoural functional heterogeneity with sunitinib treatment, revealing the presence of drug-resistant clones prior to the initiation of therapy. Multi-regional exome Matched DNA sequencing of the primary tumour and metastases revealed DNA mutational signatures associated with sunitinib resistance at baseline and after treatment. These These studies demonstrate a rapid and affordable method of findings confirm the existence of genetic and surveying functional tumour heterogeneities heterogeneity.","abstract":"Treatment of patients with advanced cancers increasingly relies on agents targeting specific molecular or cellular aberrations. These expensive therapies often fail because of pre-existing drug resistance. Intra-tumoural molecular and micro-environmental heterogeneity resistance can create resistance in one or more subclones of a tumour, leading to spatio-functional heterogeneity. We created a rapid approach for quantifying tumour functional phenotypes based on tumour-implantation into the chorioallantoic membrane of chick embryos. We apply this technique to 43 separate biopsies from 6 patients with renal cell carcinoma (RCC) with 36 replicates per biopsy, achieving a 93.6% engraftment rate (1449/1548). Challenging these models with sunitinib, an anti-angiogenic therapy frequently used in RCC allowed us to quantify spatio-functional heterogeneity in individual patients. Prediction of de novo drug resistance in advanced cancer patients would facilitate precision medicine by tailoring systemic therapies and improve clinical trial design outcome measures. We describe a patient-derived xenograft platform where fresh patient tumour samples are implanted into the chorioallantoic membrane (CAM) of chick embryos at high engraftment efficiencies, permitting large scale “tumour avatar” studies to guide the selection of drugs and to predict clinical drug resistance outcomes in renal cell carcinoma (RCC) patients. Applying this “tumour avatar” model in a co-clinical trial on RCC patients, we observe intra-tumoural functional heterogeneity with sunitinib treatment, revealing the presence of drug-resistant clones prior to the initiation of therapy. Multi-regional exome Matched DNA sequencing of the primary tumour and metastases revealed DNA mutational signatures associated with sunitinib resistance at baseline and after treatment. These These studies demonstrate a rapid and affordable method of findings confirm the existence of genetic and surveying functional tumour heterogeneities heterogeneity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-22T13:33:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002628","title":"2017_prospective_v2 Whole Exome Sequencing","description":"2017 AML prospective study contains 10 paired WES samples which were collected from SNUH.The study was designed to examine the molecular abnormalities from leukemic patients at initial diagnosis in comparison with corresponding germ line control (saliva samples). The results of WXS were analyzed by Mutect for ranking cancer variants and creating mutational matrix.","abstract":"2017 AML prospective study contains 10 paired WES samples which were collected from SNUH.The study was designed to examine the molecular abnormalities from leukemic patients at initial diagnosis in comparison with corresponding germ line control (saliva samples). The results of WXS were analyzed by Mutect for ranking cancer variants and creating mutational matrix.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-28T08:39:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002629","title":"Whole genome sequencing in Dutch melanoma families","description":"In this study we have whole-genome sequenced the germlines of 28 individuals from 6 Dutch melanoma families; 26 affected family members, 1 obligate carrier and 1 unaffected and unrelated spouse. The underlying genetic defect of these 6 melanoma families is yet unclear, by sequencing the whole genomes of these individuals we aim to identify the genetic defects that predisposes these families to melanoma.","abstract":"In this study we have whole-genome sequenced the germlines of 28 individuals from 6 Dutch melanoma families; 26 affected family members, 1 obligate carrier and 1 unaffected and unrelated spouse. The underlying genetic defect of these 6 melanoma families is yet unclear, by sequencing the whole genomes of these individuals we aim to identify the genetic defects that predisposes these families to melanoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002630","title":"Mutational spectrum of highly differentiated, fusion-negative rhabdomyosarcoma (set 1).","description":"Pediatric PAX-FOXO1 fusion-negative rhabdomyosarcoma represents a diverse spectrum of tumors. In this study, the mutational spectrum of 22 fusion-negative rhabdomyosarcomas with high, rhabdomyoma-like levels of differentiation was evaluated using OncoPanel v.2 (OPv2), an Agilent SureSelect custom designed bait set consisting of the coding regions of 504 cancer-relevant genes. Corresponding normal tissue was not available. Discarded normal human skeletal muscle, obtained from 7 donors without tumor history, were also included in the sequencing run.","abstract":"Pediatric PAX-FOXO1 fusion-negative rhabdomyosarcoma represents a diverse spectrum of tumors. In this study, the mutational spectrum of 22 fusion-negative rhabdomyosarcomas with high, rhabdomyoma-like levels of differentiation was evaluated using OncoPanel v.2 (OPv2), an Agilent SureSelect custom designed bait set consisting of the coding regions of 504 cancer-relevant genes. Corresponding normal tissue was not available. Discarded normal human skeletal muscle, obtained from 7 donors without tumor history, were also included in the sequencing run.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-28T19:27:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002631","title":"Performance comparison of three DNA extraction kits on human whole-exome data from formalin-fixed paraffin-embedded normal and tumor samples","description":"We generated 42 human whole-exome sequencing data sets from fresh-frozen (FF) and FFPE samples. These samples include normal and tumor tissues from two different organs (liver and colon), that we extracted with three different FFPE extraction kits (QIAamp DNA FFPE Tissue kit and GeneRead DNA FFPE kit from Qiagen, Maxwell\\textsuperscript{TM} RSC DNA FFPE Kit from Promega). Variant calling analysis shows a very high rate of concordance between matched FF / FFPE pairs and equivalent performance for the three kits we analyzed. We find a significant variation in the difference of total number of variants called between FF and FFPE samples for the three different FFPE DNA extraction kits. Coverage analysis shows that FFPE samples have less good indicators than FF samples, yet the coverage quality remains above accepted thresholds. We detect limited but significant variations in coverage indicator values between the three FFPE extraction kits. Globally, the GeneRead and QIAamp kits have better variant calling and coverage indicators than the Maxwell kit on the samples used in this study, although this kit performs better on some indicators and has advantages in terms of practical usage. Taken together, our results confirm the potential of FFPE samples analysis for clinical genomic studies, but also indicate that the choice of a FFPE DNA extraction kit should be done with careful testing and analysis beforehand in order to maximize the accuracy of the results.","abstract":"We generated 42 human whole-exome sequencing data sets from fresh-frozen (FF) and FFPE samples. These samples include normal and tumor tissues from two different organs (liver and colon), that we extracted with three different FFPE extraction kits (QIAamp DNA FFPE Tissue kit and GeneRead DNA FFPE kit from Qiagen, Maxwell\\textsuperscript{TM} RSC DNA FFPE Kit from Promega). Variant calling analysis shows a very high rate of concordance between matched FF / FFPE pairs and equivalent performance for the three kits we analyzed. We find a significant variation in the difference of total number of variants called between FF and FFPE samples for the three different FFPE DNA extraction kits. Coverage analysis shows that FFPE samples have less good indicators than FF samples, yet the coverage quality remains above accepted thresholds. We detect limited but significant variations in coverage indicator values between the three FFPE extraction kits. Globally, the GeneRead and QIAamp kits have better variant calling and coverage indicators than the Maxwell kit on the samples used in this study, although this kit performs better on some indicators and has advantages in terms of practical usage. Taken together, our results confirm the potential of FFPE samples analysis for clinical genomic studies, but also indicate that the choice of a FFPE DNA extraction kit should be done with careful testing and analysis beforehand in order to maximize the accuracy of the results.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-29T14:51:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002632","title":"Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome","description":"Patients with short QT syndrome (SQTS) may present with syncope, ventricular fibrillation or sudden cardiac death. Six SQTS susceptibility genes, encoding cation channels, explain less than 25% of SQTS cases. Here we identify a missense mutation in the anion exchanger (AE3)-encoding SLC4A3 gene in two unrelated families with SQTS. The mutation causes reduced surface expression of AE3 and reduced membrane bicarbonate transport. Slc4a3 knockdown in zebrafish causes increased cardiac pHi, short QTc, and reduced systolic duration, which is rescued by wildtype but not mutated SLC4A3. Mechanistic analyses suggest that an increase in pHi and decrease in [Cl-]i  shortened the action potential duration. However, other mechanisms may also play a role. Altered anion transport represents a mechanism for development of arrhythmia and may provide new therapeutic possibilities.","abstract":"Patients with short QT syndrome (SQTS) may present with syncope, ventricular fibrillation or sudden cardiac death. Six SQTS susceptibility genes, encoding cation channels, explain less than 25% of SQTS cases. Here we identify a missense mutation in the anion exchanger (AE3)-encoding SLC4A3 gene in two unrelated families with SQTS. The mutation causes reduced surface expression of AE3 and reduced membrane bicarbonate transport. Slc4a3 knockdown in zebrafish causes increased cardiac pHi, short QTc, and reduced systolic duration, which is rescued by wildtype but not mutated SLC4A3. Mechanistic analyses suggest that an increase in pHi and decrease in [Cl-]i  shortened the action potential duration. However, other mechanisms may also play a role. Altered anion transport represents a mechanism for development of arrhythmia and may provide new therapeutic possibilities.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-30T09:22:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002633","title":"_Isotype_resolved_sequencing_of_B_cell_receptor__in_sorted_memory_populations","description":"Optimisation of ex vivo Memory B cell Expansion/Differentiation for Interrogation of Rare Peripheral Memory B Cell Subset Responses\n\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Human memory B cells play a vital role in the long-term protection of the host from pathogenic rechallenge. In recent years the importance of a number of different memory B cell subsets which can be formed in response to vaccination or infection has started to become clear. To study memory B cell responses, cells can be cultured ex vivo allowing for an increase in cell number and activation of these quiescent cells, providing sufficient quantities of each memory subset to enable a full investigation of functionality. However, despite numerous papers being published demonstrating bulk memory B cell culture, we could find no literature on optimised conditions for the study of memory B cell subsets such as IgM+ memory B cells. Following a literature review we carried out a large screen of memory B cell expansion conditions to identify the combination which induced the highest levels of memory B cell expansion. We subsequently used a novel Design of Experiments approach to finely tune the optimal memory B cell expansion and differentiation conditions for human memory B cell subsets. Finally, we characterised the resultant cell populations by IgH sequencing and flow cytometre. The application of specific optimised conditions induce multiple rounds of memory B cell proliferation equally across Ig isotypes, differentiation of memory B cells to antibody secreting cells, and importantly do not alter the Ig genotype of the stimulated cells. Overall, our data identify a memory B cell culture system which offers a robust platform for investigating the functionality of rare memory B cell subsets to infection and/or vaccination.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-30T10:28:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002634","title":"Isotype_resolved_sequencing_of_B_cell_receptor__in_health_and_disease","description":"Sequencing of B-cell receptor repertoires in healthy individuals and patients with chronic lymphocytic leukemia.\n\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"The ability of humoral immune response to link  antibody  binding  diversity  and isotype  effector  functions is central to the evolution of B-cell responses and  involves rounds of somatic  hypermutation  (SHM) and  class-switch  recombination  (CSR) in B-cell receptor genes. The exact  mechanisms  of  interplay  between  SHM  and  CSR  leading  to  the  development  of  antibodies  of  different  isotypes  remain  incompletely  understood.  Here,  we  use isotype-resolved sequencing of B-cell receptor genes to  study  the  relationship  between  variable  gene  diversity  and class-switching in healthy  individuals  and  in  people  with  chronic  lymphocytic  leukaemia  (CLL).  Diversity in  healthy  repertoires  results  from  step-wise  SHM  in  variable  genes  coupled  to  class-switching  to  multiple  isotypes. Leukemic repertoires are clonally expanded but  with  reduced  variable  gene  diversity  and  minimal  class-switching, biased  towards  primary  switches. Class-switch fate of  individual  B-cell  clones  is  associated  with  their  level  of  mutation  and  variable gene  identity  leading  to  isotype-specific  signatures  of  variable  gene  usage  conserved  across  individuals.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-30T12:35:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002635","title":"Isotype_resolved_sequencing_of_B_cell_receptor_in_measles_virus_infection","description":"Isotype-resolved sequencing of B cell receptor in measles virus infection\n\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Abstract*:\nSequencing B and T cell receptor genes allows for detailed characterisation of the genetic diversity underlying adaptive immune responses in health and disease. In the context of infectious diseases this can act as a potent tool for identification of pathogen-specific immune signatures and genetic determinants of immune memory, protection and response to re-exposure. Childhood measles is characterised with strong immune activation coupled to a profound loss of circulating B cells, causing transient lymphopenia. Measles immune suppression can cause increased incidence of secondary infections up to 3 years after successful resolution of disease. Here, we apply isotype-resolved B cell receptor (BCR) sequencing to characterise the long-term changes in B cell repertoire diversity and isotype composition following natural infection with measles virus in immunologically naive individuals. We identify significant genetic restructuring of BCR repertoires in the immune memory compartment and emergence of measles-specific signatures shared between individuals. This work demonstrates the utility of immune repertoire sequencing for chatacterisation of complex immune dynamics during natural infection and provides important important insights into the specific genetic patterns of reconstitution of immune memory, following immune cell depletion.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-30T12:42:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002636","title":"Cross-tissue transcriptomic analysis of human secondary lymphoid organ residing ILC3 reveals a default quiescent state in the absence of inflammation","description":"A cross tissue transcriptional comparison of human ILC3 isolated from non-inflamed lymph nodes (LN) and spleens, inflamed tonsils and the peripheral blood (PB). Using uniform gating and high-purity cell-sorting, ILC3 were sorted as Lineage(CD3,CD19,CD34,CD14,CD94)-CD45intCD127+CRTH2-CD117+. From LN, spleen, tonsils and PB, NKp44- ILC3 were isolated and, in addition, NKp44+ ILC3 were sorted from spleen and tonsils. RNA quality was measured on a RNA 6000 Pico Kit (Agilent Technologies) using a 2100 Bioanalyzer (Agilent Technologies). 100 pg high-quality RNA was isolated and cDNA was generated using the SMART-Seq (v3) Ultra Low Input RNA Kit (Clontech) with 15 cycles of amplification. Amplified and Covaris-fragmented cDNA was quality-checked on a High Sensitivity DNA chip (Agilent Technologies) and further processed according the TruSeq Nano DNA Library Preparation Kit (Illumina). Data was processed as follows: SMARTer adapters were trimmed with cutadapt and the resulting sequences were aligned to the human RefSeq transcriptome using 14 TopHat2 (Kim et al., 2013). Normalization and quantification was performed using Cufflinks (Trapnell et al., 2012). FPKM counts were determined per gene with HTSeq-count.","abstract":"A cross tissue transcriptional comparison of human ILC3 isolated from non-inflamed lymph nodes (LN) and spleens, inflamed tonsils and the peripheral blood (PB). Using uniform gating and high-purity cell-sorting, ILC3 were sorted as Lineage(CD3,CD19,CD34,CD14,CD94)-CD45intCD127+CRTH2-CD117+. From LN, spleen, tonsils and PB, NKp44- ILC3 were isolated and, in addition, NKp44+ ILC3 were sorted from spleen and tonsils. RNA quality was measured on a RNA 6000 Pico Kit (Agilent Technologies) using a 2100 Bioanalyzer (Agilent Technologies). 100 pg high-quality RNA was isolated and cDNA was generated using the SMART-Seq (v3) Ultra Low Input RNA Kit (Clontech) with 15 cycles of amplification. Amplified and Covaris-fragmented cDNA was quality-checked on a High Sensitivity DNA chip (Agilent Technologies) and further processed according the TruSeq Nano DNA Library Preparation Kit (Illumina). Data was processed as follows: SMARTer adapters were trimmed with cutadapt and the resulting sequences were aligned to the human RefSeq transcriptome using 14 TopHat2 (Kim et al., 2013). Normalization and quantification was performed using Cufflinks (Trapnell et al., 2012). FPKM counts were determined per gene with HTSeq-count.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-30T13:03:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002637","title":"HDAC inhibitors in synovial sarcoma cells","description":"Histone deacetylase (HDAC) inhibition has been shown in previous studies to disrupt the synovial sarcoma oncoprotein complex, resulting in apoptosis. To understand the molecular effects of HDAC inhibition, RNA-Seq transcriptome analysis was undertaken in six human synovial sarcoma cell lines. HDAC inhibition induced pathways of cell cycle arrest, neuronal differentiation and response to oxygen-containing species, effects also observed in other cancers treated with this class of drugs. More specific to synovial sarcoma, polycomb-group targets were reactivated including tumor suppressor CDKN2A, and pro-apoptotic transcriptional patterns were induced. Functional analyses revealed that ROS-mediated FOXO activation and pro-apoptotic factors BIK, BIM and BMF were important to apoptosis induction following HDAC-inhibition in synovial sarcoma","abstract":"Histone deacetylase (HDAC) inhibition has been shown in previous studies to disrupt the synovial sarcoma oncoprotein complex, resulting in apoptosis. To understand the molecular effects of HDAC inhibition, RNA-Seq transcriptome analysis was undertaken in six human synovial sarcoma cell lines. HDAC inhibition induced pathways of cell cycle arrest, neuronal differentiation and response to oxygen-containing species, effects also observed in other cancers treated with this class of drugs. More specific to synovial sarcoma, polycomb-group targets were reactivated including tumor suppressor CDKN2A, and pro-apoptotic transcriptional patterns were induced. Functional analyses revealed that ROS-mediated FOXO activation and pro-apoptotic factors BIK, BIM and BMF were important to apoptosis induction following HDAC-inhibition in synovial sarcoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-08-30T18:50:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002638","title":"WGS___ENU_HT_29_BRAF_Triple_Therapy_Clones_","description":"KRAS mutant CRC is currently in clinical trial with a combination of a MEK and Akt inhibitor. These patients will likely develop resistance to this combination. We aim to identify the mechanisms of resistance via ENU mutagenesis, with a view to identifying additional therapeutics which have the ability to overcome this resistance.","abstract":"ENU used to engender resistance to a combination of a MEK inhibitor and an Akt Inhibitor, expanded and characterised as separate clones.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002639","title":"The Southern African Human Genome Programme","description":"The Southern African Human Genome Programme (SAHGP) is a national and regional initiative that aims to unlock the unique genetic character of southern African populations. Its vision is to improve quality of life through understanding human genetic diversity. It is timely to advance the SAHGP initiative since global genomic initiatives are increasingly pointing to populations in Africa, more specifically the San and Khoe from southern Africa, as harbouring the most ancient genetic signatures among the living populations of the world. Studies on African populations have already generated a wealth of information upon which the SAHGP can build. This information will be used to promote and support genomic research programmes both nationally and regionally to address critical questions that would benefit the people of our region. The SAHGP aims to make a significant contribution to the understanding of DNA variation among southern Africans and how this impacts on the health of the people of this region.\n\nAims of the SAHGP:\nTo develop capacity for genomic research in southern Africa;\nTo establish sustainable resources for genomic research in the region; and \nTo translate knowledge and information into improvements in human health in the region. \n\nThe objective is to derive the maximum benefit from the SAHGP, and that the data should be widely shared with the scientific community for the benefit of the people of the sub-continent and beyond.","abstract":"The Southern African Human Genome Programme (SAHGP) is a national and regional initiative that aims to unlock the unique genetic character of southern African populations. Its vision is to improve quality of life through understanding human genetic diversity. It is timely to advance the SAHGP initiative since global genomic initiatives are increasingly pointing to populations in Africa, more specifically the San and Khoe from southern Africa, as harbouring the most ancient genetic signatures among the living populations of the world. Studies on African populations have already generated a wealth of information upon which the SAHGP can build. This information will be used to promote and support genomic research programmes both nationally and regionally to address critical questions that would benefit the people of our region. The SAHGP aims to make a significant contribution to the understanding of DNA variation among southern Africans and how this impacts on the health of the people of this region.\n\nAims of the SAHGP:\nTo develop capacity for genomic research in southern Africa;\nTo establish sustainable resources for genomic research in the region; and \nTo translate knowledge and information into improvements in human health in the region. \n\nThe objective is to derive the maximum benefit from the SAHGP, and that the data should be widely shared with the scientific community for the benefit of the people of the sub-continent and beyond.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-04T07:52:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002640","title":"Single_cell_sequencing_of_iHOs_after_IL_22_stimulation","description":"We propose to use single cell sequencing of intestinal epithelial cells (IECs) from human induced pluripotent stem cell derived organoids (iHOs) to generate transcriptional profiles for naïve cells comprising hIPSC-derived intestinal organoids (enterocytes, goblet cells, Paneth cells and enteroendocrine cells), and to generate transcriptional profiles for the same cell subsets after IL-22 stimulation. \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We propose to use single cell sequencing of intestinal epithelial cells (IECs) from human induced pluripotent stem cell derived organoids (iHOs) to generate transcriptional profiles for naïve cells comprising hIPSC-derived intestinal organoids (enterocytes, goblet cells, Paneth cells and enteroendocrine cells), and to generate transcriptional profiles for the same cell subsets after IL-22 stimulation.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002641","title":"Genetic determinants of glycated hemoglobin levels in the Greenlandic Inuit population","description":"We recently showed that a common genetic variant leads to a remarkably increased risk of type 2 diabetes (T2D) in the small and historically isolated Greenlandic population. Motivated by this, we aimed at investigating the genetic determinants for glycated hemoglobin (HbA1C).\nWe found no novel associations but saw that for 10 out of 15 known HbA1C loci that the effects in Greenlandic Inuit were similar to previously reported.\nOne locus, ANK1, showed a significant ancestral population specific effect. \nOur results shed light on the genetics effects across ethnicites.","abstract":"We recently showed that a common genetic variant leads to a remarkably increased risk of type 2 diabetes (T2D) in the small and historically isolated Greenlandic population. Motivated by this, we aimed at investigating the genetic determinants for glycated hemoglobin (HbA1C).\nWe found no novel associations but saw that for 10 out of 15 known HbA1C loci that the effects in Greenlandic Inuit were similar to previously reported.\nOne locus, ANK1, showed a significant ancestral population specific effect. \nOur results shed light on the genetics effects across ethnicites.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-06T11:50:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002642","title":"Using_genetics_to_identify_cell_types_and_mechanisms_underlying_susceptibility_to_primary_sclerosing_cholangitis","description":"Primary sclerosing cholangitis (PSC) is a T-cell mediated, chronic inflammatory condition of the biliary tree that is strongly associated with inflammatory bowel disease. Genome-wide association studies have identified 22 non-HLA genetic risk variants associated PSC. Identifying the genes impacted by these variants has proven difficult as the majority lie in non-coding regions of the genome. Knowledge of the genes and biological pathways these non-coding variants are perturbing is vital to understanding the disease biology. One means of assessing the impact of non-coding variants within disease associated loci upon genes is via colocalisation with eQTL. Many eQTL are cell-type specific, requiring the analysis of disease relevant cell types to detect colocalisation. We have collected PSC-relevant T-cell-subtypes from the peripheral blood of PSC patients via fluorescence activated cell sorting in preparation for RNA sequencing and mapping of eQTL. Samples were collected at the Norfolk and Norwich University Hopital, for which local ethical approval has been granted. Lysed cell samples will be transferred to WTSI and DNA/RNA will be extracted from lysed cell samples by T143 before genotyping (DNA) and custom library preparation and sequencing (RNA).\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This study will help us identify the mechanisms and genes impacted by non-coding variants associated with PSC, serving to increase biological understanding of the disease and potentially identify therapeutic targets.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-07T13:55:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002643","title":"Using_genetics_to_identify_cell_types_and_mechanisms_underlying_susceptibility_to_primary_sclerosing_cholangitis","description":"Primary sclerosing cholangitis (PSC) is a T-cell mediated, chronic inflammatory condition of the biliary tree that is strongly associated with inflammatory bowel disease. Genome-wide association studies have identified 22 non-HLA genetic risk variants associated PSC. Identifying the genes impacted by these variants has proven difficult as the majority lie in non-coding regions of the genome. Knowledge of the genes and biological pathways these non-coding variants are perturbing is vital to understanding the disease biology. One means of assessing the impact of non-coding variants within disease associated loci upon genes is via colocalisation with eQTL. Many eQTL are cell-type specific, requiring the analysis of disease relevant cell types to detect colocalisation. We have collected PSC-relevant T-cell-subtypes from the peripheral blood of PSC patients via fluorescence activated cell sorting in preparation for RNA sequencing and mapping of eQTL. Samples were collected at the Norfolk and Norwich University Hopital, for which local ethical approval has been granted. Lysed cell samples will be transferred to WTSI and DNA/RNA will be extracted from lysed cell samples by T143 before genotyping (DNA) and custom library preparation and sequencing (RNA).\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This study will help us identify the mechanisms and genes impacted by non-coding variants associated with PSC, serving to increase biological understanding of the disease and potentially identify therapeutic targets.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-07T13:58:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002644","title":"RSV_infections_in_asthma_and_healthy_patients","description":"1. Different immune clel subpopulatiosn were sorted from blood and BALC sampels from heal;thy and asthma volunteers infected with RSV. Timepoints include pre infection and after 3 and 6 days.\n\n&lt;2. Please choose one of the following two standard statements to be included with your data submissions (one or the other, depending on the study). If you use the second statement, replace [doi or ref] by a reference or doi for your publication:\n\na.\tThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We aim to identify the RSV response in human lungs and blood and how that differs between healthy individuals and asthmatic individuals.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002645","title":"Genome-wide search for higher order epistasis as modifiers of treatment effects on bone mineral density in childhood cancer survivors","description":"Survivors of pediatric acute lymphoblastic leukemia (ALL) exposed to curative treatments that adversely affect BMD (age- and sex-adjusted BMD Z-scores, measured via QCT). Specifically, after SNP QC and annotation, we considered 75523 autosomal SNPs mapped to putative promoter or enhancer regions to restrict our search to 3-way SNP interactions that potentially reflect gene regulation events that influence BMD. We replicated 3-SNP interactions as modifiers of treatment effects in a cohort of adult survivors of non-ALL pediatric cancers (N=1428).","abstract":"Survivors of pediatric acute lymphoblastic leukemia (ALL) exposed to curative treatments that adversely affect BMD (age- and sex-adjusted BMD Z-scores, measured via QCT). Specifically, after SNP QC and annotation, we considered 75523 autosomal SNPs mapped to putative promoter or enhancer regions to restrict our search to 3-way SNP interactions that potentially reflect gene regulation events that influence BMD. We replicated 3-SNP interactions as modifiers of treatment effects in a cohort of adult survivors of non-ALL pediatric cancers (N=1428).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-08T02:04:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002646","title":"Identification of a Fumarate-Hydratase Deficient-like RCC Subtype with Convergent Pathway Alterations","description":"The development of molecularly targeted therapies builds upon the identification of tumor clades with shared molecular abnormalities. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a familial syndrome resulting from germline mutation of the two-hit tumor suppressor gene, Fumarate Hydratase (FH). HLRCC renal tumors present often in young adults, exhibit unique histological features and are particularly aggressive. HLRCC is uncommon and poorly understood, and whether there are sporadic renal tumors with similar characteristics, is unclear. Notably, FH can also be inactivated somatically in RCC, and should be included among FH-deficient (FHD) kidney tumors. We identified a tumor clade without FH mutations but with similar morphological and molecular characteristics as well as aggressive clinical behavior, which we name FHDL (FHD-like). We show that FHD/FHDL tumors represent a unique subtype of CIMP (CpG Island Methylator Phenotype) with the highest levels of overall genome methylation and CDKN2A silencing. FHD/FHDL tumors are characterized by convergent activation of the Hippo pathway as determined by frequent and mutually exclusive mutations in NF2 and PTPN14. AKR1B10, an NRF2 target, was upregulated in FHD/FHDL tumors as well as GATA3, which suggests a shared origin in the renal medulla and is consistent with topological studies. There is loss of 5-hydroxymethylcytosine in both FHD and FHDL tumors. These data define a group of particularly aggressive renal cancers with shared molecular features and potential targets for therapeutic intervention.","abstract":"The development of molecularly targeted therapies builds upon the identification of tumor clades with shared molecular abnormalities. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a familial syndrome resulting from germline mutation of the two-hit tumor suppressor gene, Fumarate Hydratase (FH). HLRCC renal tumors present often in young adults, exhibit unique histological features and are particularly aggressive. HLRCC is uncommon and poorly understood, and whether there are sporadic renal tumors with similar characteristics, is unclear. Notably, FH can also be inactivated somatically in RCC, and should be included among FH-deficient (FHD) kidney tumors. We identified a tumor clade without FH mutations but with similar morphological and molecular characteristics as well as aggressive clinical behavior, which we name FHDL (FHD-like). We show that FHD/FHDL tumors represent a unique subtype of CIMP (CpG Island Methylator Phenotype) with the highest levels of overall genome methylation and CDKN2A silencing. FHD/FHDL tumors are characterized by convergent activation of the Hippo pathway as determined by frequent and mutually exclusive mutations in NF2 and PTPN14. AKR1B10, an NRF2 target, was upregulated in FHD/FHDL tumors as well as GATA3, which suggests a shared origin in the renal medulla and is consistent with topological studies. There is loss of 5-hydroxymethylcytosine in both FHD and FHDL tumors. These data define a group of particularly aggressive renal cancers with shared molecular features and potential targets for therapeutic intervention.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-08T20:15:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002647","title":"The interface of malignant and immunologic clonal dynamics in high-grade serous ovarian cancer","description":"High-grade serous ovarian cancer exhibits intratumoral heterogeneity (ITH) at diagnosis which is thought to underlie resistant disease. Despite extensive ITH, metastatic spread of tumor clones is non-random, implying the existence of microenvironmental factors that shape localized tumor progression. We interrogated the molecular interface between tumor-infiltrating lymphocytes (TIL) and cancer cells in 143 samples from 21 patients with whole-genome sequencing, immunohistochemistry, histologic image analysis, gene expression, and T- and B-cell receptor sequencing. We show that mutational processes operating within cancer cells are linked to immune properties, with tumors bearing low abundance of foldback inversion rearrangements and high immune activity delineating most favorable treatment outcomes (n=433).Epithelial CD8+ TIL were associated with coupled evolutionary dynamics between immune and malignant populations, evidenced by suppressed clonal diversity, spatial tracking between T cells and tumor clones, and antigen-driven selection within B cells. Together, our findings reveal three categories of immunologic response, and that regional variation in immune contexture, potentially exploitable through immunotherapy, shapes the pattern of malignant spread within the peritoneal cavity.","abstract":"High-grade serous ovarian cancer exhibits intratumoral heterogeneity (ITH) at diagnosis which is thought to underlie resistant disease. Despite extensive ITH, metastatic spread of tumor clones is non-random, implying the existence of microenvironmental factors that shape localized tumor progression. We interrogated the molecular interface between tumor-infiltrating lymphocytes (TIL) and cancer cells in 143 samples from 21 patients with whole-genome sequencing, immunohistochemistry, histologic image analysis, gene expression, and T- and B-cell receptor sequencing. We show that mutational processes operating within cancer cells are linked to immune properties, with tumors bearing low abundance of foldback inversion rearrangements and high immune activity delineating most favorable treatment outcomes (n=433).Epithelial CD8+ TIL were associated with coupled evolutionary dynamics between immune and malignant populations, evidenced by suppressed clonal diversity, spatial tracking between T cells and tumor clones, and antigen-driven selection within B cells. Together, our findings reveal three categories of immunologic response, and that regional variation in immune contexture, potentially exploitable through immunotherapy, shapes the pattern of malignant spread within the peritoneal cavity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002648","title":"Population-level analysis of Blastocystis subtype prevalence and variation in the human gut microbiota","description":"Here, we studied well-phenotyped individuals from the Flemish Gut Flora Project (FGFP, N=616, Belgium) to characterize the profile of their gut microbiome and test associations between these profiles, presence of Blastocystis and Blastocystis subtypes.","abstract":"Here, we studied well-phenotyped individuals from the Flemish Gut Flora Project (FGFP, N=616, Belgium) to characterize the profile of their gut microbiome and test associations between these profiles, presence of Blastocystis and Blastocystis subtypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002649","title":"Transcriptional_analysis_of_cells_from_lungs","description":"To capture the full heterogeneity of the cellular types and states during HSPCs differentiation, haematopoietic progenitors will be obtained through column-enrichment of cells expressing CD34, a pan-progenitor marker for HSPCs. The samples from tumour and non-tumour lung tissue from different patients will be processed using the 10x Genomics platform. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This program of work will determine transcriptional and epigenetic changes in HSCs that are associated with the tumour niche and extramedullary haematopoiesis. Single-cell RNA-Seq of thousands of blood cells combined with the state-of-the art computational analysis will provide unparalleled insight into the mechanisms and pathways of haematopoietic cells differentiation and how these are influenced by environmental cues.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-11T10:22:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002650","title":"Ultra-fast multiplex small DNA sequencing on the MinION nanopore sequencing platform","description":"Here, we developed an ultra-rapid multiplexed library preparation and sequencing method for the MinION and applied this method to accurately test euploid and aneuploid genomic DNA samples in under three hours, including library preparation and sequencing. This novel method shows great promise as a clinical diagnostic test for applications requiring rapid short-read DNA sequencing.","abstract":"Here, we developed an ultra-rapid multiplexed library preparation and sequencing method for the MinION and applied this method to accurately test euploid and aneuploid genomic DNA samples in under three hours, including library preparation and sequencing. This novel method shows great promise as a clinical diagnostic test for applications requiring rapid short-read DNA sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-12T17:22:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002651","title":"Radiogenomics of neuroblastomas: relationships between imaging phenotypes, tumor genomic profile and survival  PONE D 17 17629","description":"Radiogenomics of neuroblastomas: relationships between imaging phenotypes, tumor genomic profile and survivalHervé J. Brisse1,2¶*, Thomas Blanc3,4¶, Gudrun Schleiermacher2,5,6&amp;, Véronique Mosseri2,7&amp;, Pascale Philippe-Chomette8,9, Isabelle Janoueix-Lerosey2,10, Gaelle Pierron2,6, Eve Lapouble5, Michel Peuchmaur9,11, Paul Fréneaux2,12, Louise Galmiche4,13, Nathalie Algret7, Matthieu Peycelon3,4, Jean Michon2,5, Olivier Delattre2,6,10 and Sabine Sarnacki3,4¶1 Imaging Department, Institut Curie, Paris, France2 Paris Sciences et Lettres Research University, Paris, France3 Department of Pediatric Surgery, Necker-Enfants-Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France4 Paris-Descartes Sorbonne-Paris-Cité University, Paris, France5 Department of Pediatric Oncology, Institut Curie, Paris, France6 Unité de Génétique Somatique, Institut Curie, Paris, France7 Department of Biostatistics, Institut Curie, Paris, France8 Department of Pediatric Surgery and Urology, Robert Debré University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France9 Paris-Diderot Sorbonne-Paris-Cité University, Paris, France10 Institut Curie, INSERM, U830, Equipe Labellisée Ligue Contre le Cancer, Paris, France11 Department of Pathology, Robert Debré University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France12 Department of Biopathology, Institut Curie, Paris, France13 Department of Pathology, Necker-Enfants-Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France","abstract":"Radiogenomics of neuroblastomas: relationships between imaging phenotypes, tumor genomic profile and survivalHervé J. Brisse1,2¶*, Thomas Blanc3,4¶, Gudrun Schleiermacher2,5,6&amp;, Véronique Mosseri2,7&amp;, Pascale Philippe-Chomette8,9, Isabelle Janoueix-Lerosey2,10, Gaelle Pierron2,6, Eve Lapouble5, Michel Peuchmaur9,11, Paul Fréneaux2,12, Louise Galmiche4,13, Nathalie Algret7, Matthieu Peycelon3,4, Jean Michon2,5, Olivier Delattre2,6,10 and Sabine Sarnacki3,4¶1 Imaging Department, Institut Curie, Paris, France2 Paris Sciences et Lettres Research University, Paris, France3 Department of Pediatric Surgery, Necker-Enfants-Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France4 Paris-Descartes Sorbonne-Paris-Cité University, Paris, France5 Department of Pediatric Oncology, Institut Curie, Paris, France6 Unité de Génétique Somatique, Institut Curie, Paris, France7 Department of Biostatistics, Institut Curie, Paris, France8 Department of Pediatric Surgery and Urology, Robert Debré University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France9 Paris-Diderot Sorbonne-Paris-Cité University, Paris, France10 Institut Curie, INSERM, U830, Equipe Labellisée Ligue Contre le Cancer, Paris, France11 Department of Pathology, Robert Debré University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France12 Department of Biopathology, Institut Curie, Paris, France13 Department of Pathology, Necker-Enfants-Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002652","title":"Childhood_arthritis_DNA","description":"The aim of this study is to describe the transcriptome of single arthritic cells.","abstract":"Here, we will study arthritic cells from children with rheumatoid disease to identify the cell types involved in mediating these disease.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-13T12:45:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002653","title":"Childhood_arthritis_RNA","description":"The aim of this study is to describe the transcriptome of single arthritic cells.","abstract":"Here, we will study arthritic cells from children with rheumatoid disease to identify the cell types involved in mediating these disease.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002654","title":"A system-wide approach to monitor responses to synergistic BRAF and EGFR inhibition in colorectal cancer cells","description":"Molecular heterogeneity of tumors, epigenetic changes and a diverse range of molecular mechanisms are main contributors to drug resistance, which represents one of the great challenges in cancer treatment. A deeper understanding of the molecular biology of cancer has resulted in better targeted therapies, where one or multiple drugs are adopted in novel therapies to tackle resistance. This beneficial effect of using combination treatments has to some extent also been observed in colorectal cancer (CRC) patients harboring the BRAF(V600E) mutation, whereby dual inhibition of BRAF(V600E) and EGFR increases antitumor activity. Notwithstanding this success, it is not clear whether this combination treatment is the only or most effective treatment to block resistance. Here, we investigate molecular responses upon single and multi-target treatments, over time, using BRAF(V600E) mutant CRC cells as a well-define model system. Through integration of transcriptomic, proteomic and phosphoproteomics data we obtain a comprehensive overview, revealing both well-known and novel responses. We primarily observe widespread upregulation of tyrosine kinases (RTKs) and and metabolic pathways. This points to by which the treated cells switch energy sources as a defensive response entering a quiescent like state, while activating signalling to re-activate the MAPK pathway.","abstract":"Molecular heterogeneity of tumors, epigenetic changes and a diverse range of molecular mechanisms are main contributors to drug resistance, which represents one of the great challenges in cancer treatment. A deeper understanding of the molecular biology of cancer has resulted in better targeted therapies, where one or multiple drugs are adopted in novel therapies to tackle resistance. This beneficial effect of using combination treatments has to some extent also been observed in colorectal cancer (CRC) patients harboring the BRAF(V600E) mutation, whereby dual inhibition of BRAF(V600E) and EGFR increases antitumor activity. Notwithstanding this success, it is not clear whether this combination treatment is the only or most effective treatment to block resistance. Here, we investigate molecular responses upon single and multi-target treatments, over time, using BRAF(V600E) mutant CRC cells as a well-define model system. Through integration of transcriptomic, proteomic and phosphoproteomics data we obtain a comprehensive overview, revealing both well-known and novel responses. We primarily observe widespread upregulation of tyrosine kinases (RTKs) and and metabolic pathways. This points to by which the treated cells switch energy sources as a defensive response entering a quiescent like state, while activating signalling to re-activate the MAPK pathway.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-13T13:46:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002655","title":"DEEP IHEC release 2017","description":"Raw data files for DEEP's IHEC/EpiRR submission of 2017.\n\nmetadata available at: http://deep.dkfz.de/#/experiments","abstract":"Raw data files for DEEP's IHEC/EpiRR submission of 2017.\n\nmetadata available at: http://deep.dkfz.de/#/experiments","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-13T16:12:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002656","title":"H3Africa - Collaborative African Genomics Network","description":"Genomic studies have become one of the potential tools that could aid in the understanding of disease. HIV disease progression and active TB infection have been studied using these genomic methods to interrogate host factors associated with these diseases and their progression. Prior work has focused on adult populations and limited African cohorts.  The Collaborative African Genomics Network aims to fill this gap by conducting HIV and TB disease mapping studies in African children to understand how genetic variation impacts disease progression through the use of genomic technologies.","abstract":"Genomic studies have become one of the potential tools that could aid in the understanding of disease. HIV disease progression and active TB infection have been studied using these genomic methods to interrogate host factors associated with these diseases and their progression. Prior work has focused on adult populations and limited African cohorts.  The Collaborative African Genomics Network aims to fill this gap by conducting HIV and TB disease mapping studies in African children to understand how genetic variation impacts disease progression through the use of genomic technologies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-14T11:34:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002657","title":"Detection of clinically relevant genetic and transcriptomic landscape in DLBCL uniformly treated by R-CHOP","description":"Recent studies using next-generation sequencing strategies have described the landscape of genetic alterations in diffuse large B-cell lymphoma (DLBCL). However, little is known about the clinical relevance of recurrent mutations and copy number alterations and their transcriptional footprints. This study examines the frequency, interaction and clinical impact of recurrent genetic aberrations in DLBCL using high-resolution technologies in a large population-based cohort.","abstract":"Recent studies using next-generation sequencing strategies have described the landscape of genetic alterations in diffuse large B-cell lymphoma (DLBCL). However, little is known about the clinical relevance of recurrent mutations and copy number alterations and their transcriptional footprints. This study examines the frequency, interaction and clinical impact of recurrent genetic aberrations in DLBCL using high-resolution technologies in a large population-based cohort.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-15T00:10:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002658","title":"Somatic_mutation_and_clonal_evolution_in_the_human_bladder_WGS","description":"In this study, we aim to characterise the landscape of mutation and clonal selection in the human bladder. The data in this study will be generated by whole-genome sequencing of laser-dissected microbiopsies from the bladder. The samples utilised in this study will include urothelium from transplant donors with no history of bladder cancer and cystectomy specimens from patients with bladder cancer.","abstract":"In this study, we aim to characterise the landscape of mutation and clonal selection in the human bladder. The data in this study will be generated by whole-genome sequencing of laser-dissected microbiopsies from the bladder. The samples utilised in this study will include urothelium from transplant donors with no history of bladder cancer and cystectomy specimens from patients with bladder cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-15T11:03:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002659","title":"Somatic_mutation_and_clonal_evolution_in_the_human_bladder_TGS","description":"In this study, we aim to characterise the landscape of mutation and clonal selection in the human bladder. The study includes targeted sequencing of laser-dissected microbiopsies from the bladder. The samples utilised in this study will include urothelium from transplant donors with no history of bladder cancer and cystectomy specimens from patients with bladder cancer.","abstract":"In this study, we aim to characterise the landscape of mutation and clonal selection in the human bladder. The study includes targeted sequencing of laser-dissected microbiopsies from the bladder. The samples utilised in this study will include urothelium from transplant donors with no history of bladder cancer and cystectomy specimens from patients with bladder cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-15T11:06:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002660","title":"RNA sequencing data of 66 matched primary and recurrent high grade serous ovarian cancer","description":"Gene expression profiles of matched primary and recurrent fresh frozen tumor tissues from 66 HGSOC patients were obtained by RNA sequencing. RNA libraries were created using the Illumina TruSeq RNA sample preparation kit V2 according to the manufacturer’s instructions and sequenced on a HiSeq2000 (Illumina, California, USA) using a V3 flowcell generating 1 x 50 bp reads. Raw sequencing reads were mapped to the transcriptome and the human reference genome (NCBI37/hg19) using TopHat 2.0 and Bowtie 2.0.","abstract":"Gene expression profiles of matched primary and recurrent fresh frozen tumor tissues from 66 HGSOC patients were obtained by RNA sequencing. RNA libraries were created using the Illumina TruSeq RNA sample preparation kit V2 according to the manufacturer’s instructions and sequenced on a HiSeq2000 (Illumina, California, USA) using a V3 flowcell generating 1 x 50 bp reads. Raw sequencing reads were mapped to the transcriptome and the human reference genome (NCBI37/hg19) using TopHat 2.0 and Bowtie 2.0.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-15T14:13:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002661","title":"Mutationa_signatures_and_clonal_dynamics_in_normal_human_tissues___TGS","description":"Somatic mutations (burdens and signatures) and clonal dynamics in normal human tissues","abstract":"The aim of this project is to investigate somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues using a cell type specific approach. We are utilising laser capture microscopy to identifiy and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002662","title":"Multisample genomic analysis of solid childhood cancers using high resolution SNP-arrays, Whole Exome Sequencing and Targeted Deep Sequencing.","description":"We mapped the prevalence of genetically distinct clones over 248 regions in 54 childhood cancers. This revealed that primary tumors can simultaneously follow up to four evolutionary patterns in different anatomic areas. The most common pattern consists of a fluctuating presence over anatomic space of subclones with very few mutations. The second most common is a surprisingly stable coexistence, over vast areas, of clones with different changes in chromosome numbers. This is contrasted by a third, less frequent, pattern where a novel clone harboring driver mutations or structural chromosome rearrangements completely replaces its progenitor. The fourth and rarest pattern is the local emergence of a myriad of clones with TP53 inactivation. Strikingly, death from disease was limited to tumors exhibiting the two latter, most dynamic patterns.","abstract":"We mapped the prevalence of genetically distinct clones over 248 regions in 54 childhood cancers. This revealed that primary tumors can simultaneously follow up to four evolutionary patterns in different anatomic areas. The most common pattern consists of a fluctuating presence over anatomic space of subclones with very few mutations. The second most common is a surprisingly stable coexistence, over vast areas, of clones with different changes in chromosome numbers. This is contrasted by a third, less frequent, pattern where a novel clone harboring driver mutations or structural chromosome rearrangements completely replaces its progenitor. The fourth and rarest pattern is the local emergence of a myriad of clones with TP53 inactivation. Strikingly, death from disease was limited to tumors exhibiting the two latter, most dynamic patterns.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-18T12:22:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002663","title":"MicroRNA expression in malignant and benign breast tissue – the Norwegian Women and Cancer study","description":"The Norwegian Women and Cancer study (NOWAC) is a prospective study which started in 1991 and includes 172 000 Norwegian women aged 30-70 years. The study is based on questionnaires with information on variables of importance to breast cancer risk. Later, about 49 500 samples of peripheral blood have been collected (the NOWAC postgenome cohort). Participants in the NOWAC postgenome cohort with a diagnosis of breast cancer have been identified, and breast cancer cases in Northern Norway diagnosed in 2004-2008 were included in this pilot study. Formalin-fixed paraffin-embedded (FFPE) tumor tissue was retrieved from the pathology labs, tissue cores were collected and RNA extracted. As normal controls, FFPE tissue from benign breast specimens (breast reductions) was included in the study. Microarray analyses of microRNA expression were perfomed by Exiqon using the 7th generation miRCURY LNA microRNA microarray system.","abstract":"The Norwegian Women and Cancer study (NOWAC) is a prospective study which started in 1991 and includes 172 000 Norwegian women aged 30-70 years. The study is based on questionnaires with information on variables of importance to breast cancer risk. Later, about 49 500 samples of peripheral blood have been collected (the NOWAC postgenome cohort). Participants in the NOWAC postgenome cohort with a diagnosis of breast cancer have been identified, and breast cancer cases in Northern Norway diagnosed in 2004-2008 were included in this pilot study. Formalin-fixed paraffin-embedded (FFPE) tumor tissue was retrieved from the pathology labs, tissue cores were collected and RNA extracted. As normal controls, FFPE tissue from benign breast specimens (breast reductions) was included in the study. Microarray analyses of microRNA expression were perfomed by Exiqon using the 7th generation miRCURY LNA microRNA microarray system.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002664","title":"Exome_trios_in_patients_with_gastroschisis","description":"Gastroschisis (MIM 230750) is a herniation of the intestines through a defect of the abdominal wall lateral to the umbilicus (usually on the right side), and it is not covered by a membrane [Ledbetter, 2012].  Gastroschisis is a congenital anomaly with increasing incidence, easy prenatal diagnosis and extremely variable postnatal outcomes.  On the basis of clinical manifestations, epidemiologic charateristics, and the presence and type of additional malformations, gastroschisis could be considered a heterogeneous condition with no gene/s discovered yet.\nThis congenital anomaly affects approximately 1-3 infancts per 10,000 live births [Calzolari et al.1995;Parker et al.,2010]  Current knowledge about causative mutations/variants.  To date, no single gene has been linked to gastroschisis.  Some publications have tried to link this malformation to variants in genes (such as AEBP1 (adipocyte enhancer binding protein) gene [Feldkamp et al,. 2012] or the VEGF-NOS3 pathway [Lammer et al., 2008].\nPreviously, a Scribble mutant mouse model (circletail) was reported to exhibit gastroschisis, however recent studies demonstrated that the Scribble knockout fetus exhibits exomphalos phenotype of gastroschisis [Carnagham et al., 2013]. \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Gastroschisis (MIM 230750) is a herniation of the intestines through a defect of the abdominal wall lateral to the umbilicus (usually on the right side), and it is not covered by a membrane [Ledbetter, 2012].  Gastroschisis is a congenital anomaly with increasing incidence, easy prenatal diagnosis and extremely variable postnatal outcomes.  On the basis of clinical manifestations, epidemiologic charateristics, and the presence and type of additional malformations, gastroschisis could be considered a heterogeneous condition with no gene/s discovered yet.\nThis congenital anomaly affects approximately 1-3 infancts per 10,000 live births [Calzolari et al.1995;Parker et al.,2010]  Current knowledge about causative mutations/variants.  To date, no single gene has been linked to gastroschisis.  Some publications have tried to link this malformation to variants in genes (such as AEBP1 (adipocyte enhancer binding protein) gene [Feldkamp et al,. 2012] or the VEGF-NOS3 pathway [Lammer et al., 2008].\nPreviously, a Scribble mutant mouse model (circletail) was reported to exhibit gastroschisis, however recent studies demonstrated that the Scribble knockout fetus exhibits exomphalos phenotype of gastroschisis [Carnagham et al., 2013].","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-19T13:06:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002665","title":"Family-based GWAS for CRSwNP","description":"AbstractOur goal was to identify genetic markers and genes associated with susceptibility to chronic rhinosinusitis with nasal polyps using a family-based genome-wide association study.MethodsPatients with CRSwNP and controls were recruited. SNP association values were generated using DFAM (implemented in PLINK) and Efficient Mixed Model Association eXpedited (EMMAX).","abstract":"AbstractOur goal was to identify genetic markers and genes associated with susceptibility to chronic rhinosinusitis with nasal polyps using a family-based genome-wide association study.MethodsPatients with CRSwNP and controls were recruited. SNP association values were generated using DFAM (implemented in PLINK) and Efficient Mixed Model Association eXpedited (EMMAX).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-19T18:06:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002666","title":"organoids","description":"In humans, the endometrium, the uterine mucosal lining,undergoes dynamic changes throughout the menstrual cycle and pregnancy. Despite the importance of the endometrium as the site of implantation and nutritional support for theconceptus, there are no long-term culture systems that recapitulate endometrial function in vitro. We adapted conditions used to establish human adult stem-cell-derived organoid cultures to generate three-dimensional cultures of normal and decidualized human endometrium (Turco et al., Nature Cell Biology, 2017). These organoids expand long-term, are genetically stable and differentiate following treatment with reproductive hormones. Single cells from both endometrium and decidua can generate a fully functional organoid. The aim of this study is to use the established organoids as a discovery model by performing single cell RNA sequencing to identify the cell types present, with a particular focus on identifying the potential stem cell population.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"The aim of this study is to use the established endometrial organoids as a discovery model by performing single cell RNA sequencing to identify the cell types present, with a particular focus on identifying the potential stem cell population. Stem cells of the endometrium have not yet been identified in humans. This study will generate results that will be of importance in understanding mechanisms of regeneration of the endometrium as well as what goes awry in endometrial diseases invovling abnormal proliferation, such as endometriosis and endometrial cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002667","title":"Immunodeficiency_","description":"We are doing single-cell RNAseq from B cells from monozygotic twins discordant for common variable immunodeficiency\n\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"We are doing single-cell RNAseq from B cells from monozygotic twins discordant for common variable immunodeficiency\n\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-20T11:49:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002668","title":"WGS of 32 paired SRCC samples","description":"Signet-ring cell carcinoma (SRCC) has specific epidemiology and oncogenesis in gastric cancer, however with no systematical investigation for prognostic genomic features. We systematically investigated the clinical characteristics of 1,868 Chinese gastric cancer patients, and found that signet-ring cell content was significantly related to multiple clinical characteristics and treatment outcomes. Next, we performed whole genome sequencing for 32 SRCC patients with &gt; 80% signet-ring cells in tumor, and identified frequent5 CLDN18-ARHGAP26/6 fusion (25%). With additional 797 patients for validation, we notice that prevalence of CLDN18-ARHGAP26/6 fusion is positively associated with signet-ring cell content (P = 4.1 x 10 -9 ), younger age at diagnosis (P = 4.2 x 10 -10 ), female/male ratio (P = 1.7 x 10 -9 ), and advanced TNM stage (P = 1.7 x 10 -5 ). Importantly, patients with CLDN18-ARHGAP26/6 fusion had a worse survival outcomes (P = 0.03), and got no benefit0 from platinum/fluoropyrimidines based chemotherapy (P = 0.92) compared to fusion-free patients (P = 0.001), which is consistent with the fact of oxaliplatin/fluoropyrimidine resistance acquired in CLDN18-ARHGAP26 introduced gastric cancer cell lines. Overall, this study provides new insights into the clinical and genomic features of SRCC, and highlights the importance of frequent CLDN18-ARHGAP26/6 fusions in chemotherapy response for SRCC.","abstract":"Signet-ring cell carcinoma (SRCC) has specific epidemiology and oncogenesis in gastric cancer, however with no systematical investigation for prognostic genomic features. We systematically investigated the clinical characteristics of 1,868 Chinese gastric cancer patients, and found that signet-ring cell content was significantly related to multiple clinical characteristics and treatment outcomes. Next, we performed whole genome sequencing for 32 SRCC patients with &gt; 80% signet-ring cells in tumor, and identified frequent5 CLDN18-ARHGAP26/6 fusion (25%). With additional 797 patients for validation, we notice that prevalence of CLDN18-ARHGAP26/6 fusion is positively associated with signet-ring cell content (P = 4.1 x 10 -9 ), younger age at diagnosis (P = 4.2 x 10 -10 ), female/male ratio (P = 1.7 x 10 -9 ), and advanced TNM stage (P = 1.7 x 10 -5 ). Importantly, patients with CLDN18-ARHGAP26/6 fusion had a worse survival outcomes (P = 0.03), and got no benefit0 from platinum/fluoropyrimidines based chemotherapy (P = 0.92) compared to fusion-free patients (P = 0.001), which is consistent with the fact of oxaliplatin/fluoropyrimidine resistance acquired in CLDN18-ARHGAP26 introduced gastric cancer cell lines. Overall, this study provides new insights into the clinical and genomic features of SRCC, and highlights the importance of frequent CLDN18-ARHGAP26/6 fusions in chemotherapy response for SRCC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-22T11:47:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002669","title":"Glioma associated stromal cells have predictive prognosis ability and harbor distinct mutations","description":"Stromal cells in the tumor microenvironment promote tumor growth, angiogenesis, inflammation and metastases. We report the isolation and unsupervised characterization of glioma-associated stromal cells (GASCs) localized prominently around abnormal tumor vasculature in adult glioma. Tumor tissue-derived stromal cells were isolated from 21 gliomas, grades II-IV. Cells were cultured as glioma stem cells or in 10% serum. We performed exome sequencing on the tumor tissue, cultures, and matched normal blood/muscle tissue from the same patients. To assess cell lineage, we performed unsupervised clustering of global DNA methylation and RNA sequencing from cultures and tumor tissue. We identified archetypal markers from GASC cultures and mapped them to expression data from anatomic structures isolated by laser microdissection from glioblastoma sections to infer localization within the tumor. Finer localization was confirmed using immunohistochemistry for FN1 EDA, a highly expressed marker of these cells.","abstract":"Stromal cells in the tumor microenvironment promote tumor growth, angiogenesis, inflammation and metastases. We report the isolation and unsupervised characterization of glioma-associated stromal cells (GASCs) localized prominently around abnormal tumor vasculature in adult glioma. Tumor tissue-derived stromal cells were isolated from 21 gliomas, grades II-IV. Cells were cultured as glioma stem cells or in 10% serum. We performed exome sequencing on the tumor tissue, cultures, and matched normal blood/muscle tissue from the same patients. To assess cell lineage, we performed unsupervised clustering of global DNA methylation and RNA sequencing from cultures and tumor tissue. We identified archetypal markers from GASC cultures and mapped them to expression data from anatomic structures isolated by laser microdissection from glioblastoma sections to infer localization within the tumor. Finer localization was confirmed using immunohistochemistry for FN1 EDA, a highly expressed marker of these cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002670","title":"We performed whole-exome sequencing of 20 samples (10 actinic keratosis and 10 cutaneous squamous cell carcinoma) to investigate a potential relationship between DNA methylation-based subtypes and genetic mutation patterns (Rodriguez-Paredes et al., Nat Commun 2017)","description":"Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer type and arises from keratinocytes. Most cSCC progress from a UV-induced precancerous lesion termed actinic keratosis (AK). Despite various efforts to characterize these lesions molecularly, the etiology of AK and its progression to cSCC remain only partially understood. Here we have used Infinium MethylationEPIC BeadChips to interrogate the DNA methylation status of about 850.000 CpGs in epidermal preparations from healthy skin, AK and cSCC. Importantly, we found that the premalignant AK samples displayed classical features of cancer methylomes and were highly similar to cSCC methylomes. Further analysis identified typical features of stem cell methylomes, such as a reduced DNA methylation age, non-CpG methylation and stem cell-related keratin and enhancer methylation patterns. Interestingly, this signature was detected only in one half of the AK and cSCC samples, while the other half showed keratin and enhancer methylation patterns that were more closely related to the control epidermis. These findings suggest the existence of two distinct subclasses of AK and cSCC that originate from distinct keratinocyte differentiation stages.","abstract":"Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer type and arises from keratinocytes. Most cSCC progress from a UV-induced precancerous lesion termed actinic keratosis (AK). Despite various efforts to characterize these lesions molecularly, the etiology of AK and its progression to cSCC remain only partially understood. Here we have used Infinium MethylationEPIC BeadChips to interrogate the DNA methylation status of about 850.000 CpGs in epidermal preparations from healthy skin, AK and cSCC. Importantly, we found that the premalignant AK samples displayed classical features of cancer methylomes and were highly similar to cSCC methylomes. Further analysis identified typical features of stem cell methylomes, such as a reduced DNA methylation age, non-CpG methylation and stem cell-related keratin and enhancer methylation patterns. Interestingly, this signature was detected only in one half of the AK and cSCC samples, while the other half showed keratin and enhancer methylation patterns that were more closely related to the control epidermis. These findings suggest the existence of two distinct subclasses of AK and cSCC that originate from distinct keratinocyte differentiation stages.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-26T13:32:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002671","title":"MicroRNA expression in malignant and benign breast tissue – the Norwegian Women and Cancer study","description":"The Norwegian Women and Cancer study (NOWAC) is a prospective study which started in 1991 and includes 172 000 Norwegian women aged 30-70 years. The study is based on questionnaires with information on variables of importance to breast cancer risk. Later, about 49 500 samples of peripheral blood have been collected (the NOWAC postgenome cohort). Participants in the NOWAC postgenome cohort with a diagnosis of breast cancer have been identified, and breast cancer cases in Northern Norway diagnosed in 2004-2008 were included in this pilot study. Formalin-fixed paraffin-embedded (FFPE) tumor tissue was retrieved from the pathology labs, tissue cores were collected and RNA extracted. As normal controls, FFPE tissue from benign breast specimens (breast reductions) was included in the study. Microarray analyses of microRNA expression were perfomed by Exiqon using the 7th generation miRCURY LNA microRNA microarray system.od- to be deleted","abstract":"The Norwegian Women and Cancer study (NOWAC) is a prospective study which started in 1991 and includes 172 000 Norwegian women aged 30-70 years. The study is based on questionnaires with information on variables of importance to breast cancer risk. Later, about 49 500 samples of peripheral blood have been collected (the NOWAC postgenome cohort). Participants in the NOWAC postgenome cohort with a diagnosis of breast cancer have been identified, and breast cancer cases in Northern Norway diagnosed in 2004-2008 were included in this pilot study. Formalin-fixed paraffin-embedded (FFPE) tumor tissue was retrieved from the pathology labs, tissue cores were collected and RNA extracted. As normal controls, FFPE tissue from benign breast specimens (breast reductions) was included in the study. Microarray analyses of microRNA expression were perfomed by Exiqon using the 7th generation miRCURY LNA microRNA microarray system.od- to be deleted","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-26T15:13:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002672","title":"test","description":"test","abstract":"test","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002673","title":"MicroRNA expression in malignant and benign breast tissue – the Norwegian Women and Cancer study","description":"The Norwegian Women and Cancer study (NOWAC) is a prospective study which started in 1991 and includes 172 000 Norwegian women aged 30-70 years. The study is based on questionnaires with information on variables of importance to breast cancer risk. Later, about 49 500 samples of peripheral blood have been collected (the NOWAC postgenome cohort). Participants in the NOWAC postgenome cohort with a diagnosis of breast cancer have been identified, and breast cancer cases in Northern Norway diagnosed in 2004-2008 were included in this pilot study. Formalin-fixed paraffin-embedded (FFPE) tumor tissue was retrieved from the pathology labs, tissue cores were collected and RNA extracted. As normal controls, FFPE tissue from benign breast specimens (breast reductions) was included in the study. Microarray analyses of microRNA expression were perfomed by Exiqon using the 7th generation miRCURY LNA microRNA microarray system.","abstract":"The Norwegian Women and Cancer study (NOWAC) is a prospective study which started in 1991 and includes 172 000 Norwegian women aged 30-70 years. The study is based on questionnaires with information on variables of importance to breast cancer risk. Later, about 49 500 samples of peripheral blood have been collected (the NOWAC postgenome cohort). Participants in the NOWAC postgenome cohort with a diagnosis of breast cancer have been identified, and breast cancer cases in Northern Norway diagnosed in 2004-2008 were included in this pilot study. Formalin-fixed paraffin-embedded (FFPE) tumor tissue was retrieved from the pathology labs, tissue cores were collected and RNA extracted. As normal controls, FFPE tissue from benign breast specimens (breast reductions) was included in the study. Microarray analyses of microRNA expression were perfomed by Exiqon using the 7th generation miRCURY LNA microRNA microarray system.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002674","title":"Y_phylogeny_haplogroupDE","description":"High-coverage whole genome sequences using Hiseq X for 4 individuals to investigate their Y chrosmosmes' relationship to the known phylogeny. \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Detailed study of haplogroup DE human Y chromosomes using high-coverage whole genome sequences to understand the human migrations","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-28T13:45:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002675","title":"FCA_Blood","description":"We are doing single-cell RNAseq from adult skin to study new cell populations and their functions.\n\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"This project aims to deconstruct the human skin to its individual cellular constituents using single cell technologies. In this pursuit, we will define the cell census and functional niches within the human skin","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002676","title":"Liver biopsy derived induced pluripotent stem cells provide an unlimited supply for the generation of patient-specific hepatocyte-like cells","description":"Background: Hepatocyte-like cells (HLCs) differentiated from induced pluripotent stem cells (iPSCs) have emerged as a promising cell culture model to study metabolism, biotransformation, viral infections and genetic liver diseases. However the derivation of iPSCs is restricted by ethical and procedural constraints. Furthermore, incomplete HLC differentiation remains a major challenge. iPSC may carry-on a tissue of origin dependent expression memory influencing iPSC differentiation into different cell types. If liver derived iPSCs (Li-iPSCs) maintain a liver specific gene expression profile is not known. It is also not known, if Li-iPSCs would allow the generation of more fully differentiated HLCs.Methods: Primary liver cells (PLCs) were expanded from liver needle biopsies and reprogrammed into Li-iPSCs using a non-integrative Sendai virus-based system. Li-iPSCs were differentiated into HLCs using established differentiation protocols. The HLC phenotype was characterized at the protein, functional and transcriptional level. RNA sequencing data were generated from the originating liver biopsies, the Li-iPSCs, fibroblast derived iPSCs, and differentiated HLCs, and used to characterize and compare their transcriptome profiles.Results: PLCs were obtained from small pieces of liver biopsies and could be reprogrammed into Li-iPSCs. Li-iPSCs indeed retain a liver specific transcriptional footprint. Li-iPSCs can be propagated to provide an unlimited supply of cells for differentiation into Li-HLCs. Similar to HLCs derived from fibroblasts, Li-HLCs could not be fully differentiated into hepatocytes. Relative to the originating liver, Li-HLCs showed lower expression of liver specific transcription factors and increased expression of genes involved in the differentiation of other tissues.Conclusions: PLCs and Li-iPSCs obtained from small pieces of human needle liver biopsies constitute a novel unlimited source for the production of HLCs. Despite the preservation of a liver specific gene expression footprint in Li-iPSCs, the generation of fully differentiated hepatocytes cannot be achieved with the current differentiation protocols.","abstract":"Background: Hepatocyte-like cells (HLCs) differentiated from induced pluripotent stem cells (iPSCs) have emerged as a promising cell culture model to study metabolism, biotransformation, viral infections and genetic liver diseases. However the derivation of iPSCs is restricted by ethical and procedural constraints. Furthermore, incomplete HLC differentiation remains a major challenge. iPSC may carry-on a tissue of origin dependent expression memory influencing iPSC differentiation into different cell types. If liver derived iPSCs (Li-iPSCs) maintain a liver specific gene expression profile is not known. It is also not known, if Li-iPSCs would allow the generation of more fully differentiated HLCs.Methods: Primary liver cells (PLCs) were expanded from liver needle biopsies and reprogrammed into Li-iPSCs using a non-integrative Sendai virus-based system. Li-iPSCs were differentiated into HLCs using established differentiation protocols. The HLC phenotype was characterized at the protein, functional and transcriptional level. RNA sequencing data were generated from the originating liver biopsies, the Li-iPSCs, fibroblast derived iPSCs, and differentiated HLCs, and used to characterize and compare their transcriptome profiles.Results: PLCs were obtained from small pieces of liver biopsies and could be reprogrammed into Li-iPSCs. Li-iPSCs indeed retain a liver specific transcriptional footprint. Li-iPSCs can be propagated to provide an unlimited supply of cells for differentiation into Li-HLCs. Similar to HLCs derived from fibroblasts, Li-HLCs could not be fully differentiated into hepatocytes. Relative to the originating liver, Li-HLCs showed lower expression of liver specific transcription factors and increased expression of genes involved in the differentiation of other tissues.Conclusions: PLCs and Li-iPSCs obtained from small pieces of human needle liver biopsies constitute a novel unlimited source for the production of HLCs. Despite the preservation of a liver specific gene expression footprint in Li-iPSCs, the generation of fully differentiated hepatocytes cannot be achieved with the current differentiation protocols.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-28T20:12:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002677","title":"Transcriptomics_of_immune_cells","description":"In this study we will compare the single cell transcriptomes of immune cells from the peripheral blood of healthy individuals.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Various white blood cell types have so far undescribed heterogeneity in the population, which could explain the functional aspects of the immune system. We have chosen different cell types for RNA sequencing study in order to describe that heterogeneity on the level of global gene expression. The cells are sorted from peripheral blood mononuclear cells via FACS by using multiple color tags in order to gain pure populations of cell types and gain additional layer of data for describing heterogeneity of the surface markers.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002678","title":"Genome-wide analysis of genetic risk factors for rheumatic heart disease in Aboriginal Australians provides support for pathogenic molecular mimicry","description":"Background. Rheumatic heart disease (RHD) following Group A Streptococcus (GAS) infections is heritable and prevalent in Indigenous populations. Molecular mimicry between human and GAS proteins triggers pro-inflammatory cardiac valve-reactive T-cells. Methods. Genome-wide genetic analysis was undertaken in 1263 Aboriginal Australians (398 RHD cases; 865 controls). Single nucleotide polymorphisms (SNPs) were genotyped using Illumina HumanCoreExome BeadChips.  Direct typing and imputation was used to fine-map the human leukocyte antigen (HLA) region. Epitope binding affinities were mapped for human cross-reactive GAS proteins, including M5 and M6.   Results. The strongest genetic association was intronic to HLA-DQA1 (rs9272622; P=1.86x10-7). Conditional analyses showed rs9272622 and/or DQA1*AA16 account for the HLA signal. HLA-DQA1*0101_DQB1*0503 (OR 1.44, 95%CI 1.09-1.90, P=9.56x10-3) and HLA-DQA1*0103_DQB1*0601 (OR 1.27, 95%CI 1.07-1.52, P=7.15x10-3) were risk haplotypes; HLA_DQA1*0301-DQB1*0402 (OR 0.30, 95%CI 0.14-0.65, P=2.36x10-3) was protective.  Human myosin cross-reactive N-terminal and B repeat epitopes of GAS M5/M6 bind with higher affinity to DQA1/DQB1 alpha/beta dimers for the two risk haplotypes than the protective haplotype.  Conclusions. Variation at HLA_DQA1-DQB1 is the major genetic risk factor for RHD in Aboriginal Australians studied here. Cross-reactive epitopes bind with higher affinity to alpha/beta dimers formed by risk haplotypes, supporting molecular mimicry as the key mechanism of RHD pathogenesis.","abstract":"Background. Rheumatic heart disease (RHD) following Group A Streptococcus (GAS) infections is heritable and prevalent in Indigenous populations. Molecular mimicry between human and GAS proteins triggers pro-inflammatory cardiac valve-reactive T-cells. Methods. Genome-wide genetic analysis was undertaken in 1263 Aboriginal Australians (398 RHD cases; 865 controls). Single nucleotide polymorphisms (SNPs) were genotyped using Illumina HumanCoreExome BeadChips.  Direct typing and imputation was used to fine-map the human leukocyte antigen (HLA) region. Epitope binding affinities were mapped for human cross-reactive GAS proteins, including M5 and M6.   Results. The strongest genetic association was intronic to HLA-DQA1 (rs9272622; P=1.86x10-7). Conditional analyses showed rs9272622 and/or DQA1*AA16 account for the HLA signal. HLA-DQA1*0101_DQB1*0503 (OR 1.44, 95%CI 1.09-1.90, P=9.56x10-3) and HLA-DQA1*0103_DQB1*0601 (OR 1.27, 95%CI 1.07-1.52, P=7.15x10-3) were risk haplotypes; HLA_DQA1*0301-DQB1*0402 (OR 0.30, 95%CI 0.14-0.65, P=2.36x10-3) was protective.  Human myosin cross-reactive N-terminal and B repeat epitopes of GAS M5/M6 bind with higher affinity to DQA1/DQB1 alpha/beta dimers for the two risk haplotypes than the protective haplotype.  Conclusions. Variation at HLA_DQA1-DQB1 is the major genetic risk factor for RHD in Aboriginal Australians studied here. Cross-reactive epitopes bind with higher affinity to alpha/beta dimers formed by risk haplotypes, supporting molecular mimicry as the key mechanism of RHD pathogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-29T09:14:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002679","title":"Employing_single_cell_sequencing_for_detection_of_mutational_signatures_reflecting_on_going_mutagenesis_","description":"12 single cells will be sequenced from a previously single-cell derived clone of a JSC-1 cell line. Additional 12 single cells are likely to be sequenced from a previously single-cell derived clone of a SW756 line. Both belong to CGP’s panel of approximately 1000 human cancer cell lines.","abstract":"Mutational catalogues employed to extract mutational signatures represent archaeological traces of mutational processes that were once operative.  These processes may continue to operate, operate in transient bursts or no longer be operative.  Our previous experiments explored those options by employing dozens of cell lines with mutational signatures of interest that were subcloned over a defined period of time and sequenced. The increased load of the mutations representative of a specific mutational signature within the genome of a subclone when compared to its parental clone was informative of the on-going mutational processes. These experiments suggested that already single-cell derived parental clones may discriminate between those lines that do and do not contain an ongoing mutagenesis. Cell lines with an ongoing mutagenesis represent a biological resource for future studies on the molecular origins of mutational signatures found in human cancer. \n\nMutations captured by previously employed sequencing of a single-cell derived clone from a cancer cell lines reflect mainly those mutations present in a single cell ancestral to that clone.  Therefore, sequencing of a single-cell derived clone, may be replaced with a straightforward sequencing of individual cells. In order to infer in which of the human cancer cell lines processes generating signatures 2 and 13 remain operative, we will employ exome-sequencing of single cells from cancer cell lines with a high mutational burden attributed to those signatures. This pilot project serves to assess the feasibility of a potential larger-scale experiment outlined above. The pilot will therefore only encompass sequencing of single cells from cell lines known to have or not to have a mutational process on-going in order to evaluate the ability of detecting clear mutational signatures in exomes of individual cells.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-29T10:28:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002680","title":"WGS___Exploration_of__mutational_processes_in_human_cancer_cell_lines","description":"Approximately 25 cell lines representative of 11 mutation signatures have been selected and will be grown from a single cell, referred to as parental clone, for a period of 3 months to allow accumulation of mutations. Following that period, we will obtain 2 subclones from each of the parental clone for analysis by exome-sequencing . In total we will therefore be sequencing 2 parental clones and 4 subclones per cell line for approximately 25 cell lines.  Once the data has been analysed and the potential ongoing mutation processes determined, we will perform whole-genome sequencing of the parental clones and subclones of the candidate cell lines.","abstract":"One of the key questions to be explored is whether the biological processes generating specific mutational signatures continue to operate in the human cancer cell lines or simply reflect past mutagenic activity which is no longer operative. To address this question, we have extracted mutational signatures from 1,000 cancer cell lines of diverse cancer types. Several cell lines with mutational signatures of interest will be selected, subcloned over a defined period of time and their exomes sequenced. The increased load of the mutations representative of a specific mutational signature within the genome of a subclone when compared to its parental clone will be informative of the on-going mutational processes. To further confirm our observation from the exome-sequencing pilot project, whole genomes from parental clones and subclones of the cell lines with potentially on-going mutational processes will be sequenced.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-09-29T10:30:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002681","title":"Genome-wide mutational consequences of nucleotide excision repair-deficiency through XPC deletion in a human adult stem cell culture","description":"Nucleotide excision repair (NER) is one of the main DNA repair pathways that protect cells against genomic damage. Deficiency in this pathway can contribute to the development of cancer and accelerate aging. NER-deficiency is an important determinant for cancer treatment outcome, as NER-deficient tumors are selectively sensitive to cisplatin treatment. While NER-deficiency has been linked to mutational Signature 5, not all NER-deficient tumors are characterized by a high Signature 5 contribution, illustrating the importance to further characterize the mutational consequences of NER-deficiency. Here, we analyzed the mutational profile of a human adult stem cell (organoid) culture that is deficient in NER through XPC deletion by CRISPR-Cas9 gene-editing, and subsequent whole-genome sequencing analysis of a clonally derived organoid. We found that XPC deletion results in an increase in base substitution load and specifically induces Signature 8 mutations, a mutational signature with previously unknown etiology. Presence of Signature 8 may, therefore, serve as a novel biomarker for NER-deficient tumors and could improve personalized treatment strategies.","abstract":"Nucleotide excision repair (NER) is one of the main DNA repair pathways that protect cells against genomic damage. Deficiency in this pathway can contribute to the development of cancer and accelerate aging. NER-deficiency is an important determinant for cancer treatment outcome, as NER-deficient tumors are selectively sensitive to cisplatin treatment. While NER-deficiency has been linked to mutational Signature 5, not all NER-deficient tumors are characterized by a high Signature 5 contribution, illustrating the importance to further characterize the mutational consequences of NER-deficiency. Here, we analyzed the mutational profile of a human adult stem cell (organoid) culture that is deficient in NER through XPC deletion by CRISPR-Cas9 gene-editing, and subsequent whole-genome sequencing analysis of a clonally derived organoid. We found that XPC deletion results in an increase in base substitution load and specifically induces Signature 8 mutations, a mutational signature with previously unknown etiology. Presence of Signature 8 may, therefore, serve as a novel biomarker for NER-deficient tumors and could improve personalized treatment strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-10-02T11:15:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002682","title":"The identification of genetic vulnerabilities in head and neck cancers for the development of novel treatments.","description":"The global cancer burden is expected to double by the year 2030 and this will disproportionately affect the Asian continent. Head and neck squamous cell carcinoma (HNSCC) is endemic in Asia. It is the sixth most common cancer worldwide and the second most common in Malaysia, with approximately 600,000 new cases per year globally. Longterm survival remains less than 50%, underscoring the need for better therapeutic strategies. In this proposal we aim to bring new technological advancements in the identification of critical genes in HNSCC and the identification of compounds for the development of new therapies in HNSCC. We propose to genomically characterise 16 unique Asian H&amp;N cancer cell lines,  to classify sub groups where identification of essential genes that can be targeted for tumor control can be applied in a more rational way. Further, we propose to use zebrafish, an established drug discovery platform to identify promising pathway-specific compounds that could be further studied using CRISPR/Cas9 lethality screens and biological models to better identify novel therapeutic strategies to combat this major health problem in Asia.","abstract":"The global cancer burden is expected to double by the year 2030 and this will disproportionately affect the Asian continent. Head and neck squamous cell carcinoma (HNSCC) is endemic in Asia. It is the sixth most common cancer worldwide and the second most common in Malaysia, with approximately 600,000 new cases per year globally. Longterm survival remains less than 50%, underscoring the need for better therapeutic strategies. In this proposal we aim to bring new technological advancements in the identification of critical genes in HNSCC and the identification of compounds for the development of new therapies in HNSCC. We propose to genomically characterise 16 unique Asian H&amp;N cancer cell lines,  to classify sub groups where identification of essential genes that can be targeted for tumor control can be applied in a more rational way. Further, we propose to use zebrafish, an established drug discovery platform to identify promising pathway-specific compounds that could be further studied using CRISPR/Cas9 lethality screens and biological models to better identify novel therapeutic strategies to combat this major health problem in Asia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-10-03T14:38:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002683","title":"Comprehensive molecular portraits of male breast cancer.","description":"Purpose: Male breast cancer is extremely rare and accounts for less than 1% of all breast malignancies. Therefore, clinical management of breast cancer in males is currently guided by research on the disease in females, despite possible differences in pathogenesis, biology and genetics.Experimental Design: A discovery cohort of 45 male breast cancers (FFPE-derived) and a validation cohort of 90 MBC (52 FFPE and 38 FF-derived) were subjected to massively parallel sequencing targeting all exons of 1943 cancer-related genes. The landscape of somatic mutations, germline mutations and copy number alterations was compared to that of subtype-matched female breast cancers (smFBC) and correlated to prognosis.Results: Within the combined discovery and validation cohort, 90% of MBCs showed ductal histology, 96% were estrogen receptor positive, 66% were progesterone receptor positive, and 2% HER2-positive, resulting in 50%, 46% and 4% luminal A-like, luminal B-like and basal-like cases, respectively. The MBC cohort included 5 patients with Klinefelter syndrome (KS; 4%). The discovery set included none and 5 (11%) patients with pathogenic germline mutations in BRCA1 and BRCA2, respectively.The genomic landscape of MBC to some extent recapitulated the smFBC landscape, with recurrent PIK3CA (31%) and GATA3 (9%) mutations, and with 40% of the most frequently amplified genes overlapping between both sexes. TP53 (2%) somatic mutations were significantly less frequent in MBC compared to smFBC whereas KMT2C (38%), HER2 (20%), NCOR1 (16%), TBL1XR1 (13%), BRCA1 (9%) and BRCA2 (9%) somatic mutations were more frequent. Overall, genes regulating chromatin function and DNA damage response seemed more often affected in MBC. High mutational load, but not copy number variation load, independently correlated with poor survival (p=0.021). MDM2 amplifications were frequent (11%), correlated with protein overexpression (p=0.001) and poor survival (p=0.007), and might thus represent an alternative mechanism for p53 inactivation in MBC. In addition, PAK1 (p=0.023), ASH1L (p=0.001) and E2F7 (p=0.009) independently predicted poor survival in MBC when amplified.The majority of BRCA2 germline mutation carriers presented with poorly differentiated tumors, with a high 8q amplification load. In contrast to BRCA2 germline mutation carriers presenting at a similar age as non-mutation carriers, subjects with KS tended to be younger at presentation, with generally well-differentiated, PR positive, and copy number and mutation naive tumors.Conclusion: Despite similarities in the genomic landscape between MBC and FBC, it is becoming increasingly clear that MBC is a molecularly unique disease requiring its own clinical trials (e.g. MDM2 inhibitors) and treatment guidelines. The molecular analysis of MBCs that we report here significantly extends our knowledge base to produce a comprehensive catalogue of likely genomic drivers, therapeutic targets, and putative prognostic and predictive markers for this rare disease.","abstract":"Purpose: Male breast cancer is extremely rare and accounts for less than 1% of all breast malignancies. Therefore, clinical management of breast cancer in males is currently guided by research on the disease in females, despite possible differences in pathogenesis, biology and genetics.Experimental Design: A discovery cohort of 45 male breast cancers (FFPE-derived) and a validation cohort of 90 MBC (52 FFPE and 38 FF-derived) were subjected to massively parallel sequencing targeting all exons of 1943 cancer-related genes. The landscape of somatic mutations, germline mutations and copy number alterations was compared to that of subtype-matched female breast cancers (smFBC) and correlated to prognosis.Results: Within the combined discovery and validation cohort, 90% of MBCs showed ductal histology, 96% were estrogen receptor positive, 66% were progesterone receptor positive, and 2% HER2-positive, resulting in 50%, 46% and 4% luminal A-like, luminal B-like and basal-like cases, respectively. The MBC cohort included 5 patients with Klinefelter syndrome (KS; 4%). The discovery set included none and 5 (11%) patients with pathogenic germline mutations in BRCA1 and BRCA2, respectively.The genomic landscape of MBC to some extent recapitulated the smFBC landscape, with recurrent PIK3CA (31%) and GATA3 (9%) mutations, and with 40% of the most frequently amplified genes overlapping between both sexes. TP53 (2%) somatic mutations were significantly less frequent in MBC compared to smFBC whereas KMT2C (38%), HER2 (20%), NCOR1 (16%), TBL1XR1 (13%), BRCA1 (9%) and BRCA2 (9%) somatic mutations were more frequent. Overall, genes regulating chromatin function and DNA damage response seemed more often affected in MBC. High mutational load, but not copy number variation load, independently correlated with poor survival (p=0.021). MDM2 amplifications were frequent (11%), correlated with protein overexpression (p=0.001) and poor survival (p=0.007), and might thus represent an alternative mechanism for p53 inactivation in MBC. In addition, PAK1 (p=0.023), ASH1L (p=0.001) and E2F7 (p=0.009) independently predicted poor survival in MBC when amplified.The majority of BRCA2 germline mutation carriers presented with poorly differentiated tumors, with a high 8q amplification load. In contrast to BRCA2 germline mutation carriers presenting at a similar age as non-mutation carriers, subjects with KS tended to be younger at presentation, with generally well-differentiated, PR positive, and copy number and mutation naive tumors.Conclusion: Despite similarities in the genomic landscape between MBC and FBC, it is becoming increasingly clear that MBC is a molecularly unique disease requiring its own clinical trials (e.g. MDM2 inhibitors) and treatment guidelines. The molecular analysis of MBCs that we report here significantly extends our knowledge base to produce a comprehensive catalogue of likely genomic drivers, therapeutic targets, and putative prognostic and predictive markers for this rare disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002684","title":"Characterization of genetic intratumor heterogeneity in colorectal cancer and matching patient-derived spheroid cultures.","description":"Patient-derived in vitro cultures of colorectal cancer (CRC) may help guide treatment strategies prior to patient treatment. However, most previous studies have been performed on a single biopsy per tumor. The purpose of this study was to analyze multiple spatially distinct biopsies from CRCs and see how well intratumor heterogeneity (ITH) was recapitulated in matching patient-derived spheroids. Three to five biopsies were collected from six CRC tumors. Each biopsy was split in two; one half was used for spheroid culturing, the other half was used for direct DNA and RNA purification. For two of the patients, lymph node metastases were analyzed. Somatic mutations were called from whole exome sequencing data. Each tumor contained multiple mutations shared across all biopsies and spheroids, including major CRC drivers such as APC, KRAS, and TP53. At the same time, all tumors exhibited ITH on both mutation and copy number level. The concordance between biopsies and spheroids ranged between 40-70% for coding mutations. For three of the patients the biopsy and spheroid from matching areas clustered together, meaning that the spheroid resembled the area of origin more than the other areas. However, all biopsies and spheroids contained private mutations. Thereby, multiple cultures from spatially distinct sites of the tumor increase the insight into the genetic profile of the entire tumor. RNA sequencing based molecular subtyping was stable and seemed independent of genetic ITH. In conclusion, all examined CRC tumors contained genetic ITH on mutation and copy number level. Spheroid cultures partly reflected this ITH, meaning that multiple cultures from distinct sites of the tumor improved the representation of the different genetic subclones in the primary tumor. This should be taken in to account when establishing patient-derived models for drug screening.","abstract":"Patient-derived in vitro cultures of colorectal cancer (CRC) may help guide treatment strategies prior to patient treatment. However, most previous studies have been performed on a single biopsy per tumor. The purpose of this study was to analyze multiple spatially distinct biopsies from CRCs and see how well intratumor heterogeneity (ITH) was recapitulated in matching patient-derived spheroids. Three to five biopsies were collected from six CRC tumors. Each biopsy was split in two; one half was used for spheroid culturing, the other half was used for direct DNA and RNA purification. For two of the patients, lymph node metastases were analyzed. Somatic mutations were called from whole exome sequencing data. Each tumor contained multiple mutations shared across all biopsies and spheroids, including major CRC drivers such as APC, KRAS, and TP53. At the same time, all tumors exhibited ITH on both mutation and copy number level. The concordance between biopsies and spheroids ranged between 40-70% for coding mutations. For three of the patients the biopsy and spheroid from matching areas clustered together, meaning that the spheroid resembled the area of origin more than the other areas. However, all biopsies and spheroids contained private mutations. Thereby, multiple cultures from spatially distinct sites of the tumor increase the insight into the genetic profile of the entire tumor. RNA sequencing based molecular subtyping was stable and seemed independent of genetic ITH. In conclusion, all examined CRC tumors contained genetic ITH on mutation and copy number level. Spheroid cultures partly reflected this ITH, meaning that multiple cultures from distinct sites of the tumor improved the representation of the different genetic subclones in the primary tumor. This should be taken in to account when establishing patient-derived models for drug screening.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-10-04T08:40:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002685","title":"WGS of breast cancer diagnosed during pregnancy and matched control","description":"The aim of this study was to compare the mutational landscape of breast cancer diagnosed during pregnancy (BCP) and breast cancer from age/stage non-pregnant patients (controls). We present whole genome sequencing data (Illumina HiSeq X ten platform) of tumor and matched normal tissues from 35 BCP patients and 20 controls. This work provides important novel biological insights and a unique resource to study the biology of breast cancer in young women and how pregnancy could modulate tumor biology.","abstract":"The aim of this study was to compare the mutational landscape of breast cancer diagnosed during pregnancy (BCP) and breast cancer from age/stage non-pregnant patients (controls). We present whole genome sequencing data (Illumina HiSeq X ten platform) of tumor and matched normal tissues from 35 BCP patients and 20 controls. This work provides important novel biological insights and a unique resource to study the biology of breast cancer in young women and how pregnancy could modulate tumor biology.","study_type":"Other","pubmed_ids":[30109263],"external_links":null,"is_released":true,"released_date":"2017-10-05T09:46:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002686","title":"DNA Methylation data for UCL Bladder cancer project","description":"Bladder cancer (BC) is one of the most common cancers in the western world and ranks as the most expensive to manage, due to the need for cystoscopic examination. BC show frequent changes in DNA methylation and several studies have shown the potential utility of urinary biomarkers by detecting epigenetic alterations in voided urine. The aim of this study is to assess the epigenetic diversity in bladder cancer to improve the detection and surveillance of bladder cancer","abstract":"Bladder cancer (BC) is one of the most common cancers in the western world and ranks as the most expensive to manage, due to the need for cystoscopic examination. BC show frequent changes in DNA methylation and several studies have shown the potential utility of urinary biomarkers by detecting epigenetic alterations in voided urine. The aim of this study is to assess the epigenetic diversity in bladder cancer to improve the detection and surveillance of bladder cancer","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002687","title":"Differential Presence of Exons in Cell-Free DNA Reveals Different Patterns in Colorectal Cancer Between Metastatic and Non-Metastatic Patients","description":"Tumor genotyping during disease follow-up is gaining an increasing interest for monitoring and clinical management in colorectal cancer (CRC). Growing evidences suggest that single biopsies are inefficient for molecular profiling, due to clonal evolution and intratumoral heterogeneity of primary tumors and/or metastasis. Circulating free DNA (cfDNA) has emerged as an alternative source of genetic material that seems to be representative of the continuously changing tumor molecular features. Thus, the so-called 'liquid biopsy' also offers the additional advantages of accessibility and non-invasiveness for the patient. Novel strategies based on next-generation sequencing (NGS) of cfDNA are being currently developed, with most studies focusing on targeted deep sequencing panels of potential clinically actionable genes. Here we describe an alternative approach, consisting of exome-sequencing in cfDNA at a relatively shallower depth to provide a more general overview of the circulating genome. In this study, two groups of colorectal cancer patients, with either disseminated (M) or localized disease (N), were compared using whole-exome sequencing and a RNA-seq bioinformatics analysis pipeline. Thus, a set of 379 exons present at different levels in cfDNA from both groups were identified, giving rise to a completely new concept in this field, termed as 'Differential Presence of Exons'. Differentially present exons (DPEs) were subsequently used for M and N patients clustering and classification, allowing for the design of a predictive algorithm with encouraging preliminary results in a small subset of patients that could not be initially classified attending to the selection criteria (U group, unassignable).","abstract":"Tumor genotyping during disease follow-up is gaining an increasing interest for monitoring and clinical management in colorectal cancer (CRC). Growing evidences suggest that single biopsies are inefficient for molecular profiling, due to clonal evolution and intratumoral heterogeneity of primary tumors and/or metastasis. Circulating free DNA (cfDNA) has emerged as an alternative source of genetic material that seems to be representative of the continuously changing tumor molecular features. Thus, the so-called 'liquid biopsy' also offers the additional advantages of accessibility and non-invasiveness for the patient. Novel strategies based on next-generation sequencing (NGS) of cfDNA are being currently developed, with most studies focusing on targeted deep sequencing panels of potential clinically actionable genes. Here we describe an alternative approach, consisting of exome-sequencing in cfDNA at a relatively shallower depth to provide a more general overview of the circulating genome. In this study, two groups of colorectal cancer patients, with either disseminated (M) or localized disease (N), were compared using whole-exome sequencing and a RNA-seq bioinformatics analysis pipeline. Thus, a set of 379 exons present at different levels in cfDNA from both groups were identified, giving rise to a completely new concept in this field, termed as 'Differential Presence of Exons'. Differentially present exons (DPEs) were subsequently used for M and N patients clustering and classification, allowing for the design of a predictive algorithm with encouraging preliminary results in a small subset of patients that could not be initially classified attending to the selection criteria (U group, unassignable).","study_type":"Other","pubmed_ids":[29573240],"external_links":null,"is_released":true,"released_date":"2017-10-06T09:06:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002688","title":"PairedOrganoids_PDX_WG","description":"DNA Sequencing of matched blood, PDX and organoids derived form metastatic colorectal cancer patients will be sequenced to identify genetic alterations conferring resistance to targeted drugs.","abstract":"Matched blood, PDX and organoids derived form therapy-refractory metastatic colorectal cancer patients.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002689","title":"IsogenicOrganoid_WG","description":"DNA Sequencing of isogenic organoids generated by CRISPR/Cas9 system.","abstract":"Isogenic organoids will be used to dissect the molecular and biological functions of CRC-related genetic alterations and to identify genotype-specific vulnerabilities which could be exploited therapeutically using genetic and pharmacological screening.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002690","title":"__IsogenicOrganoid_RNA_Seq","description":"RNA Sequencing of isogenic organoids generated by CRISPR/Cas9 system.","abstract":"Isogenic organoids will be used to dissect the molecular and biological functions of CRC-related genetic alterations and to identify genotype-specific vulnerabilities which could be exploited therapeutically using genetic and pharmacological screening.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002691","title":"Development_of_Metrics_and_Quality_Standards_for_Scale_up_of_Human_Pluripotent_Stem_Cells_","description":"RNA sequencing of iPSC and hES cells looking to set up culture standards to culture iPSC large scale using automation.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Expansion and banking of \"off the shelf\" allogeneic human pluripotent stem cell (hPSC)-derived lineages poses a realistic option for tissue repair, affordable to public/private health care systems. However, the regenerative medicine community currently lacks affordable and scalable systems. This bottleneck for translational programs requires novel solutions as a matter of urgency, with the availability of clinical grade human embryonic stem cell, and in the near future human induced pluripotent stem cell, lines. The overarching goal of this proposal is the development and qualification of a novel system for the automated scale up of hPSCs invented by Tokyo Electron (EU base in Stevenage), for subsequent differentiation into therapeutically valuable lineages. The novel, entirely enclosed, automated culture system suitable for next generation stem cell therapy manufacturing will use real time non-invasive image evaluation and biochemical/genetic monitoring to allow evaluation of cell health and phenotype during cell expansion. Thus, only healthy cells can be selected for continued culture or entry into therapeutic differentiation protocols. In this proposal we will develop the metrics to ensure optimal conditions for stable expanded hPSC culture, including growth rates/phenotype and karyotypic/epigenetic normality. Deep phenotyping will include cell morphology via refinement of computer algorithms, genetic (e.g.CGH array), transcriptomic and epigenetic profiling and both discovery and targeted secretome metabolite/proteome analysis. Pluripotency will be assured via development of high throughput novel differentiation marker analysis with a view to replacing teratoma formation with which it will be compared. We will generate new biomarkers based on culture medium analysis (secretome, biosensor data) to refine culture conditions and generate new media/substrate combinations. We will deliver online/Cloud-based metrics analysis tools available to UK/ other stem cell communities adaptable for other scale up applications.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002692","title":"Wilms_Tumour_organoid_sequencing_WGS","description":"This study investigates the genomic and transcriptomic characteristics of Wilm's tumour organoids","abstract":"This study investigates the genomic and transcriptomic characteristics of Wilm's tumour organoids","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-10-06T15:51:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002693","title":"Wilms_Tumour_organoid_sequencing_RNAseq","description":"This study investigates the genomic and transcriptomic characteristics of Wilm's tumour organoids","abstract":"This study investigates the genomic and transcriptomic characteristics of Wilm's tumour organoids","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002694","title":"MMR (DNA mismatch repair) pathway in human samples","description":"This data are related to the manuscript by Germano et al. Ms2016-04-06029","abstract":"This data are related to the manuscript by Germano et al. Ms2016-04-06029","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-10-06T17:12:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002695","title":"Papillary thyroid cancer in Saudi Arabian population","description":"Although papillary thyroid cancer constitutes a significant health burden in Saudi Arabia, it is a poorly understood tumor and this tumor type is largely under- researched. Thyroid cancer is the most common endocrine malignancy and differentiated thyroid cancer (DTC), which includes papillary (PTC) and follicular (FTC) subtypes, accounts for 90% of all thyroid malignancies  In Saudi Arabia, thyroid cancer ranked second only to breast cancer among females, eleventh among males and this increased incidence is prevalent in other Gulf Council Countries (GCC) also. Most patients with DTC do well with traditional therapy which includes total thyroidectomy, radioiodine ablation (RAI) and thyroid hormone suppression. However, some will go on to develop progressive disease that is not amenable to further surgery and/or not responsive to RAI. Currently, there are no clinical or molecular diagnostic tools to predict recurrence and aggressiveness of a subset of PTC. We aim to analyze the genomic DNA sequences of 500 thyroid cancers and the corresponding DNA from blood. With the goal of a better understanding the pathobiology of thyroid carcinogenesis we will use state of the art \"deep sequencing\" technology to decipher the molecular and genetic signature of Saudi PTC. The development of next-generation (NextGen) sequencing technologies has spurred high hopes for the identification of novel biomarkers for disease diagnosis, prognosis, and prediction, including thyroid cancer.  Our objectives will be achieved through the following aims: the studies of specific aim 1 will be the generation of comprehensive catalogues of genomic abnormalities (somatic mutations) in thyroid cancer of the papillary thyroid carcinoma histology subtype which is of clinical and social importance in Saudi Arabia. Specific aim 2 will catalogue for each papillary thyroid carcinoma to include the full range of somatic mutations including single-nucleotide variants, insertions, deletions, copy number changes, translocations and other chromosomal rearrangements. Specific aim 3 will generate complementary catalogues of transcriptomic and epigenomic datasets from selected tumor cases that demonstrate abnormalities from aim 1 and 2.  The outcome of this study will provide a better understanding of PTC and should have important clinical implications, as it could result in the development of new and better strategies for targeted therapeutic intervention for the treatment of Saudi Arabian PTC tumors.","abstract":"Although papillary thyroid cancer constitutes a significant health burden in Saudi Arabia, it is a poorly understood tumor and this tumor type is largely under- researched. Thyroid cancer is the most common endocrine malignancy and differentiated thyroid cancer (DTC), which includes papillary (PTC) and follicular (FTC) subtypes, accounts for 90% of all thyroid malignancies  In Saudi Arabia, thyroid cancer ranked second only to breast cancer among females, eleventh among males and this increased incidence is prevalent in other Gulf Council Countries (GCC) also. Most patients with DTC do well with traditional therapy which includes total thyroidectomy, radioiodine ablation (RAI) and thyroid hormone suppression. However, some will go on to develop progressive disease that is not amenable to further surgery and/or not responsive to RAI. Currently, there are no clinical or molecular diagnostic tools to predict recurrence and aggressiveness of a subset of PTC. We aim to analyze the genomic DNA sequences of 500 thyroid cancers and the corresponding DNA from blood. With the goal of a better understanding the pathobiology of thyroid carcinogenesis we will use state of the art \"deep sequencing\" technology to decipher the molecular and genetic signature of Saudi PTC. The development of next-generation (NextGen) sequencing technologies has spurred high hopes for the identification of novel biomarkers for disease diagnosis, prognosis, and prediction, including thyroid cancer.  Our objectives will be achieved through the following aims: the studies of specific aim 1 will be the generation of comprehensive catalogues of genomic abnormalities (somatic mutations) in thyroid cancer of the papillary thyroid carcinoma histology subtype which is of clinical and social importance in Saudi Arabia. Specific aim 2 will catalogue for each papillary thyroid carcinoma to include the full range of somatic mutations including single-nucleotide variants, insertions, deletions, copy number changes, translocations and other chromosomal rearrangements. Specific aim 3 will generate complementary catalogues of transcriptomic and epigenomic datasets from selected tumor cases that demonstrate abnormalities from aim 1 and 2.  The outcome of this study will provide a better understanding of PTC and should have important clinical implications, as it could result in the development of new and better strategies for targeted therapeutic intervention for the treatment of Saudi Arabian PTC tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002696","title":"Therapeutic Targeting of Ependymoma as Informed by Oncogenic Enhancer Profiling","description":"Genomic sequencing has driven precision-based oncology therapy; however, genetic drivers remain unknown or non-targetable for many malignancies, demanding alternative approaches to identify therapeutic leads. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Here, we mapped active chromatin landscapes in 42 primary ependymomas in two non-overlapping primary ependymoma cohorts. Enhancer regions revealed novel oncogenes, molecular targets, and pathways, which when subjected to small molecule inhibitor or shRNA treatment, increased survival and slowed proliferation in mouse and neurosphere patient-derived models of ependymomas. This study represents one of the largest enhancer mapping study of any cancer type to date, and provides a framework for target and drug discovery for other cancers recalcitrant to therapeutic development because of their lack of known genetic drivers.","abstract":"Genomic sequencing has driven precision-based oncology therapy; however, genetic drivers remain unknown or non-targetable for many malignancies, demanding alternative approaches to identify therapeutic leads. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Here, we mapped active chromatin landscapes in 42 primary ependymomas in two non-overlapping primary ependymoma cohorts. Enhancer regions revealed novel oncogenes, molecular targets, and pathways, which when subjected to small molecule inhibitor or shRNA treatment, increased survival and slowed proliferation in mouse and neurosphere patient-derived models of ependymomas. This study represents one of the largest enhancer mapping study of any cancer type to date, and provides a framework for target and drug discovery for other cancers recalcitrant to therapeutic development because of their lack of known genetic drivers.","study_type":"Other","pubmed_ids":[29258295],"external_links":null,"is_released":true,"released_date":"2017-10-10T12:54:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002697","title":"Alternative splicing isoforms in patient-derived hepatocellular carcinoma cells","description":"The aim of this study was to obtain a landscape of alternative splicing (AS) in human hepatocellular carcinoma (HCC). We applied hybrid sequencing by integrating Pacbio long-read and Illumina short-read RNA sequencing data from 8 patient-derived HCC cell lines, and used an immortalized hepatocyte cell line as reference. This study revealed features of annotated and novel splice variants in HCC cells, including transcript length, AS type and protein changes. We also identified novel isoforms and tumor specific isoforms, which may represent potential biomarkers and targets for therapeutic development.","abstract":"The aim of this study was to obtain a landscape of alternative splicing (AS) in human hepatocellular carcinoma (HCC). We applied hybrid sequencing by integrating Pacbio long-read and Illumina short-read RNA sequencing data from 8 patient-derived HCC cell lines, and used an immortalized hepatocyte cell line as reference. This study revealed features of annotated and novel splice variants in HCC cells, including transcript length, AS type and protein changes. We also identified novel isoforms and tumor specific isoforms, which may represent potential biomarkers and targets for therapeutic development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-10-11T15:44:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002698","title":"Gut microbiome modulates response to anti PD1 immunotherapy in metastatic melanoma patients","description":"There is a growing appreciation of the role of the microbiome in cancer, and evidence in pre-clinical models that the gut microbiome may modulate responses to immune checkpoint blockade though this has not been well-characterized in patients. We analyzed the oral (n=86)and gut (n=43) 16S microbiome in melanoma patients on PD-1 blockade. Significant differences were noted in the diversity and composition of the gut microbiome between responders and non-responders in patients with a fecal microbiome sample, with significantly higher alpha diversity and relative abundance of Ruminococcaceae bacteria) in R. Metagenomic studies (n=25) revealed functional differences in gut bacteria in R including enrichment of anabolic pathways. Immune profiling demonstrated enhanced systemic and anti-tumor immunity in patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplant from responding patients. Together, these data have important implications for treatment with immune checkpoint blockade in cancer.\n\nThe fastq files associated with this dataset are stored at ENA under the following accession numbers: PRJEB22894 (Fecal 16S), PRJEB22874 (Oral 16S), PRJEB22895 (Murine 16S), PRJEB22893 (Fecal WGS).","abstract":"There is a growing appreciation of the role of the microbiome in cancer, and evidence in pre-clinical models that the gut microbiome may modulate responses to immune checkpoint blockade though this has not been well-characterized in patients. We analyzed the oral (n=86)and gut (n=43) 16S microbiome in melanoma patients on PD-1 blockade. Significant differences were noted in the diversity and composition of the gut microbiome between responders and non-responders in patients with a fecal microbiome sample, with significantly higher alpha diversity and relative abundance of Ruminococcaceae bacteria) in R. Metagenomic studies (n=25) revealed functional differences in gut bacteria in R including enrichment of anabolic pathways. Immune profiling demonstrated enhanced systemic and anti-tumor immunity in patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplant from responding patients. Together, these data have important implications for treatment with immune checkpoint blockade in cancer.\n\nThe fastq files associated with this dataset are stored at ENA under the following accession numbers: PRJEB22894 (Fecal 16S), PRJEB22874 (Oral 16S), PRJEB22895 (Murine 16S), PRJEB22893 (Fecal WGS).","study_type":"Other","pubmed_ids":[29097493],"external_links":null,"is_released":true,"released_date":"2017-10-11T16:04:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002699","title":"TCR β-chain repertoire characterization of regulatory and conventional T cells in peripheral blood from breast cancer patients and healthy individuals.","description":"Identification of tumor-specific effects on peripheral TCRβ repertoire formation in humans, investigation of the clonal origin of regulatory T cells in breast cancer patients and impact analysis of the tumor-specific conversion of conventional T cells into induced regulatory T cells on the peripheral Treg repertoire in humans.","abstract":"Identification of tumor-specific effects on peripheral TCRβ repertoire formation in humans, investigation of the clonal origin of regulatory T cells in breast cancer patients and impact analysis of the tumor-specific conversion of conventional T cells into induced regulatory T cells on the peripheral Treg repertoire in humans.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-10-12T12:04:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002700","title":"Genome-wide DNA Methylation is Predictive of Outcome in Juvenile Myelomonocytic Leukemia","description":"Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative disorder of childhood caused by mutations in the Ras pathway. Outcomes in this disease vary dramatically from spontaneous resolution with little or no treatment to rapid relapse after hematopoietic stem cell transplantation. Given the high morbidity and late effects of transplant, it is critical to identify patients at diagnosis who can be observed rather than transplanted. We hypothesized that assessing DNA methylation status would help predict disease outcome. Genome-wide DNA methylation profiling using the Illumina 450k platform in a discovery cohort of 39 patients was performed. Unsupervised hierarchical clustering based on the most highly variable CpG sites identified three clusters of patients. Importantly, these clusters differed significantly in terms of 4-year event-free survival, with the lowest methylation cluster having the highest rates of survival. These findings were validated in an independent cohort of 40 patients. Of particular interest is that all but one of fourteen patients experiencing spontaneous resolution of their disease clustered together and closer to 22 healthy controls than the other JMML cases. This study demonstrates that DNA methylation patterns in JMML are predictive of outcome in this heterogeneously behaving disease and can identify patients who are most likely to experience spontaneous resolution.","abstract":"Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative disorder of childhood caused by mutations in the Ras pathway. Outcomes in this disease vary dramatically from spontaneous resolution with little or no treatment to rapid relapse after hematopoietic stem cell transplantation. Given the high morbidity and late effects of transplant, it is critical to identify patients at diagnosis who can be observed rather than transplanted. We hypothesized that assessing DNA methylation status would help predict disease outcome. Genome-wide DNA methylation profiling using the Illumina 450k platform in a discovery cohort of 39 patients was performed. Unsupervised hierarchical clustering based on the most highly variable CpG sites identified three clusters of patients. Importantly, these clusters differed significantly in terms of 4-year event-free survival, with the lowest methylation cluster having the highest rates of survival. These findings were validated in an independent cohort of 40 patients. Of particular interest is that all but one of fourteen patients experiencing spontaneous resolution of their disease clustered together and closer to 22 healthy controls than the other JMML cases. This study demonstrates that DNA methylation patterns in JMML are predictive of outcome in this heterogeneously behaving disease and can identify patients who are most likely to experience spontaneous resolution.","study_type":"Other","pubmed_ids":[29259179],"external_links":null,"is_released":true,"released_date":"2017-10-13T22:42:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002701","title":"Single_cell_sequencing_of_pediatric_arthritis","description":"We performed single cell analysis of cells from blood and synovial fluid of children suffering from unindentified arthritis","abstract":"We performed single cell analysis of cells from blood and synovial fluid of children suffering from unindentified arthritis. With this we aim to obtain better understanding of the disease status of these patients and how they can be treated","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002702","title":"Multi-omics data of 1000 Inflammatory Bowel Disease patients","description":"Portal available at https://1000ibd.org\n\nInflammatory bowel disease (IBD) is a chronic complex disease of the gastrointestinal (GI) tract. Patients with IBD can experience a wide range of symptoms, but the pathophysiological mechanisms that cause these individual differences in clinical presentation remain largely unknown. In consequence, IBD is currently classified into subtypes using clinical characteristics. If we are to develop a more targeted treatment approach, molecular subtypes of IBD need to be discovered that can be used as new drug targets. To achieve this, we need multiple layers of molecular data are generated from the same IBD patients.We initiated the 1000IBD project to prospectively follow more than 1000 IBD patients from the Northern provinces of the Netherlands. For these patients, we have collected a uniquely large number of phenotypes and generated multi-omics profiles. To date, 1,215 participants have been enrolled in the project and enrolment is on-going, with 609 patients being present in the first data release. Phenotype data collected for these participants includes information on dietary and environmental factors, drug responses, and adverse drug events. Genome information has been generated using genotyping (ImmunoChip, Global Screening Array and HumanExomeChip) and sequencing (whole exome sequencing and targeted resequencing of IBD susceptibility loci), transcriptome information generated using RNA-sequencing of intestinal biopsies and microbiome information generated using both sequencing of the 16S rRNA gene and whole genome shotgun metagenomic sequencing.All molecular data generated within the 1000IBD project will be shared in multiple data on the European Genome-Phenome Archive (www.ega-archive.org). The first data release, will contain basic phenotypes for 609 participants, genotypes of 314 participants, gut microbiome data generated by tag sequencing the 16S gene of feces from 315 participants and intestinal biopsies from 107 participants, and gut microbiome metagenomic sequencing of feces of 355 participants . Future releases will comprise many more additional phenotypes and -omics data layers. 1000IBD data can be used by other researchers as a replication cohort, a dataset to test new software tools, or a dataset for applying new statistical models.","abstract":"Portal available at https://1000ibd.org\n\nInflammatory bowel disease (IBD) is a chronic complex disease of the gastrointestinal (GI) tract. Patients with IBD can experience a wide range of symptoms, but the pathophysiological mechanisms that cause these individual differences in clinical presentation remain largely unknown. In consequence, IBD is currently classified into subtypes using clinical characteristics. If we are to develop a more targeted treatment approach, molecular subtypes of IBD need to be discovered that can be used as new drug targets. To achieve this, we need multiple layers of molecular data are generated from the same IBD patients.We initiated the 1000IBD project to prospectively follow more than 1000 IBD patients from the Northern provinces of the Netherlands. For these patients, we have collected a uniquely large number of phenotypes and generated multi-omics profiles. To date, 1,215 participants have been enrolled in the project and enrolment is on-going, with 609 patients being present in the first data release. Phenotype data collected for these participants includes information on dietary and environmental factors, drug responses, and adverse drug events. Genome information has been generated using genotyping (ImmunoChip, Global Screening Array and HumanExomeChip) and sequencing (whole exome sequencing and targeted resequencing of IBD susceptibility loci), transcriptome information generated using RNA-sequencing of intestinal biopsies and microbiome information generated using both sequencing of the 16S rRNA gene and whole genome shotgun metagenomic sequencing.All molecular data generated within the 1000IBD project will be shared in multiple data on the European Genome-Phenome Archive (www.ega-archive.org). The first data release, will contain basic phenotypes for 609 participants, genotypes of 314 participants, gut microbiome data generated by tag sequencing the 16S gene of feces from 315 participants and intestinal biopsies from 107 participants, and gut microbiome metagenomic sequencing of feces of 355 participants . Future releases will comprise many more additional phenotypes and -omics data layers. 1000IBD data can be used by other researchers as a replication cohort, a dataset to test new software tools, or a dataset for applying new statistical models.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-10-23T10:49:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002703","title":"The integrated genomic and immune landscapes of lethal metastatic breast cancer.","description":"We report on the extensive molecular profiling of multiple individual metastases from 10 warm autopsies of patients with lethal multi-therapy resistant breast cancers.","abstract":"We report on the extensive molecular profiling of multiple individual metastases from 10 warm autopsies of patients with lethal multi-therapy resistant breast cancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-10-23T11:00:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002704","title":"Dynamics of neoantigen landscape during immunotherapy","description":"Immune checkpoint inhibitors have shown significant therapeutic responses against tumors containing increased mutation-associated neoantigen load. We have examined the evolving landscape of tumor neoantigens during the emergence of acquired resistance in non-small cell lung cancer patients after initial response to immune checkpoint blockade with anti-PD1 or anti-PD-1/anti-CTLA4 antibodies. Analyses of matched pretreatment and resistant tumors identified genomic changes resulting in loss of 7 to 18 putative mutation-associated neoantigens in resistant clones. Peptides generated from the eliminated neoantigens elicited clonal T cell expansion in autologous T cell cultures, suggesting that they generated functional immune responses. Neoantigen loss occurred through elimination of tumor subclones or through deletion of chromosomal regions containing truncal alterations and were associated with changes in T cell receptor clonality. These analyses provide insights into the dynamics of mutational landscapes during immune checkpoint blockade and have implications for development of immune therapies that target tumor neoantigens.","abstract":"Immune checkpoint inhibitors have shown significant therapeutic responses against tumors containing increased mutation-associated neoantigen load. We have examined the evolving landscape of tumor neoantigens during the emergence of acquired resistance in non-small cell lung cancer patients after initial response to immune checkpoint blockade with anti-PD1 or anti-PD-1/anti-CTLA4 antibodies. Analyses of matched pretreatment and resistant tumors identified genomic changes resulting in loss of 7 to 18 putative mutation-associated neoantigens in resistant clones. Peptides generated from the eliminated neoantigens elicited clonal T cell expansion in autologous T cell cultures, suggesting that they generated functional immune responses. Neoantigen loss occurred through elimination of tumor subclones or through deletion of chromosomal regions containing truncal alterations and were associated with changes in T cell receptor clonality. These analyses provide insights into the dynamics of mutational landscapes during immune checkpoint blockade and have implications for development of immune therapies that target tumor neoantigens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-10-23T15:47:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002705","title":"Whole exome sequencing of cell-free DNA reveals temporo-spatial heterogeneity and identifies treatment-resistant clones in neuroblastoma","description":"Background: Neuroblastoma (NB) displays important clinical and genetic heterogeneity, with emergence of new mutations at tumor progression. Patients and Methods: To study clonal evolution during treatment and follow-up, an innovative method based on circulating cell-free DNA (cfDNA) analysis by whole exome sequencing (WES) paired with target sequencing was realized in sequential liquid biopsy samples of 19 NB patients. Results: WES of the primary tumor and cfDNA at diagnosis showed overlap of Single Nucleotide Variants (SNVs) and Copy Number Alterations (CNAs), with 41% and 93% of all detected alterations common to the primary NB and cfDNA. CfDNA WES at a second time point indicated a mean of 22 new SNVs for patients with progressive disease. Relapse-specific alterations included genes of the MAPK pathway and targeted the protein kinase A signaling pathway. Deep coverage target sequencing of intermediate timepoints during treatment and follow-up identified distinct subclones. For 17 seemingly relapse-specific SNVs detected by sequencing detected these alterations in minor subclones, with relapse-emerging SNVs targeting genes of neuritogenesis and cell cycle. Furthermore a persisting, resistant clone with concomitant disappearance of other clones was identified by a mutation in the ubiquitin protein ligase HERC2. Conclusion: Modelisation of mutated allele fractions in cfDNA indicated distinct patterns of clonal evolution, with either a minor, treatment-resistant clone expanding to a major clone at relapse, or minor clones collaborating towards tumor progression. Identification of treatment-resistant clones will enable development of more efficient treatment strategies.cfDNA WES at relapse but not tumor or cfDNA WES at diagnosis, deep coverage target.","abstract":"Background: Neuroblastoma (NB) displays important clinical and genetic heterogeneity, with emergence of new mutations at tumor progression. Patients and Methods: To study clonal evolution during treatment and follow-up, an innovative method based on circulating cell-free DNA (cfDNA) analysis by whole exome sequencing (WES) paired with target sequencing was realized in sequential liquid biopsy samples of 19 NB patients. Results: WES of the primary tumor and cfDNA at diagnosis showed overlap of Single Nucleotide Variants (SNVs) and Copy Number Alterations (CNAs), with 41% and 93% of all detected alterations common to the primary NB and cfDNA. CfDNA WES at a second time point indicated a mean of 22 new SNVs for patients with progressive disease. Relapse-specific alterations included genes of the MAPK pathway and targeted the protein kinase A signaling pathway. Deep coverage target sequencing of intermediate timepoints during treatment and follow-up identified distinct subclones. For 17 seemingly relapse-specific SNVs detected by sequencing detected these alterations in minor subclones, with relapse-emerging SNVs targeting genes of neuritogenesis and cell cycle. Furthermore a persisting, resistant clone with concomitant disappearance of other clones was identified by a mutation in the ubiquitin protein ligase HERC2. Conclusion: Modelisation of mutated allele fractions in cfDNA indicated distinct patterns of clonal evolution, with either a minor, treatment-resistant clone expanding to a major clone at relapse, or minor clones collaborating towards tumor progression. Identification of treatment-resistant clones will enable development of more efficient treatment strategies.cfDNA WES at relapse but not tumor or cfDNA WES at diagnosis, deep coverage target.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-10-25T12:46:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002706","title":"Pilot_Fetal_Cell_Atlas___DNA","description":"As part of the Human Cell Atlas we will study foetal and maternal tissue.","abstract":"The foetal cell atlas aims to generate a comprehensive atlas of cells during human development.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002707","title":"Sequencing-based counting and size profiling of plasma Epstein-Barr virus DNA enhance population screening of nasopharyngeal carcinoma.","description":"Circulating tumor-derived DNA testing for cancer screening has recently been demonstrated in a prospective study on identification of nasopharyngeal carcinoma (NPC) among 20,174 asymptomatic individuals. Plasma EBV DNA, a marker for NPC, was detected using real-time PCR. While plasma EBV DNA was persistently detectable in 97.1% of the NPCs identified, ∼5% of the general population had transiently detectable plasma EBV DNA. We hypothesized that EBV DNA in plasma of subjects with or without NPC may have different molecular characteristics. We performed target-capture sequencing of plasma EBV DNA and identified differences in the abundance and size profiles of EBV DNA molecules within plasma of NPC and non-NPC subjects. NPC patients had significantly higher amounts of plasma EBV DNA, which showed longer fragment lengths. Cutoff values were established from an exploratory dataset and tested in a validation sample set. Adopting an algorithm that required a sample to concurrently pass cutoffs for EBV DNA counting and size measurements, NPCs were detected at a positive predictive value (PPV) of 19.6%. This represented superior performance compared with the PPV of 11.0% in the prospective screening study, which required participants with an initially detectable plasma EBV DNA result to be retested within 4 weeks. The observed differences in the molecular nature of EBV DNA molecules in plasma of subjects with or without NPC were successfully translated into a sequencing-based test that had a high PPV for NPC screening and achievable through single time-point testing.","abstract":"Circulating tumor-derived DNA testing for cancer screening has recently been demonstrated in a prospective study on identification of nasopharyngeal carcinoma (NPC) among 20,174 asymptomatic individuals. Plasma EBV DNA, a marker for NPC, was detected using real-time PCR. While plasma EBV DNA was persistently detectable in 97.1% of the NPCs identified, ∼5% of the general population had transiently detectable plasma EBV DNA. We hypothesized that EBV DNA in plasma of subjects with or without NPC may have different molecular characteristics. We performed target-capture sequencing of plasma EBV DNA and identified differences in the abundance and size profiles of EBV DNA molecules within plasma of NPC and non-NPC subjects. NPC patients had significantly higher amounts of plasma EBV DNA, which showed longer fragment lengths. Cutoff values were established from an exploratory dataset and tested in a validation sample set. Adopting an algorithm that required a sample to concurrently pass cutoffs for EBV DNA counting and size measurements, NPCs were detected at a positive predictive value (PPV) of 19.6%. This represented superior performance compared with the PPV of 11.0% in the prospective screening study, which required participants with an initially detectable plasma EBV DNA result to be retested within 4 weeks. The observed differences in the molecular nature of EBV DNA molecules in plasma of subjects with or without NPC were successfully translated into a sequencing-based test that had a high PPV for NPC screening and achievable through single time-point testing.","study_type":"Other","pubmed_ids":[29760067],"external_links":null,"is_released":true,"released_date":"2017-10-27T08:35:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002708","title":"Targeted_sequencing_of_cylindroma_patients","description":"Patients with cylindroma show multiple large tumours on the scalp and forehead.  These large tumours will allow us to look at clonality within a tumour.   We wish to asses the mutational load and diversity within and across tumours as well as compare with perilesional skin.","abstract":"Patients with cylindroma show multiple large tumours on the scalp and forehead.  These large tumours will allow us to look at clonality within a tumour.   We wish to asses the mutational load and diversity within and across tumours as well as compare with perilesional skin.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-10-27T12:43:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002709","title":"Comprehensive genomic profiling of matched glioblastoma tumours, cell-lines, and xenografts reveals genomic stability and adaptation to disparate growth environments","description":"The mandate of this project was to use drug screening to deliver new drugs for glioblastoma (GBM) to clinical trials, and perform genomic assessment of GBM to discover new therapeutic targets and predictors of response. The sequencing data in this set was derived from GBM patient tumor samples, matched brain tumor initiating cells lines (BTICs), and tumor tissue derived from orthotopic implants.","abstract":"The mandate of this project was to use drug screening to deliver new drugs for glioblastoma (GBM) to clinical trials, and perform genomic assessment of GBM to discover new therapeutic targets and predictors of response. The sequencing data in this set was derived from GBM patient tumor samples, matched brain tumor initiating cells lines (BTICs), and tumor tissue derived from orthotopic implants.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-10-28T00:16:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002710","title":"Warm_PM_oesophagus_re_probe","description":"We wish to re-probe libraries from human oesophagus with a new bait set based on genes of interest identified from sequencing mouse oesophagus.","abstract":"We have indentified several genes of interest in mouse oesophagus which may play a role in clonal evolution .  We wish to re-probe a previously bait captured library from human oesophagus with a new bait set based on the genes of interest found in mice.  This will give us insights into the similarities/ differences in mutation burden and clonal dynamics between humans and mouse.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002711","title":"CD56bright natural killer cells stimulated by interleukin-2 in vivo possess an immunoregulatory phenotype and preferentially kill effector T cells over T regulatory cells","description":"We investigated the phenotype and function of CD56bright NK cells ex vivo and in vitro following IL-2 treatment. We show that in vivo IL-2 stimulation promotes CD56bright NK cell division and switches off inflammatory gene expression. In vitro they kill activated Teffs more efficiently than Tregs following IL-2 stimulation, a difference that is mediated in part by increased HLA-E expression on Tregs. Hence, IL-2 therapy may not only improve Treg suppression but also enhance the innate regulatory pathway mediated by CD56bright NK cells.","abstract":"We investigated the phenotype and function of CD56bright NK cells ex vivo and in vitro following IL-2 treatment. We show that in vivo IL-2 stimulation promotes CD56bright NK cell division and switches off inflammatory gene expression. In vitro they kill activated Teffs more efficiently than Tregs following IL-2 stimulation, a difference that is mediated in part by increased HLA-E expression on Tregs. Hence, IL-2 therapy may not only improve Treg suppression but also enhance the innate regulatory pathway mediated by CD56bright NK cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002712","title":"Adult_blood","description":"We are doing single-cell RNAseq from adult blood to study new cell populations and their functions.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"This project aims to deconstruct the human blood to its individual cellular constituents using single cell technologies. In this pursuit, we will define the cell census and functional niches within the human blood","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002713","title":"Previous studies identified epigenetic changes in iPSC-DAn derived PD patient harboring LRRK2 mutations and in sporadic PD cases without no causative mutation identified wide methylation changes by using the Infinium Human Methylation 450K BeadChip Kit (Illumina). Here, we extend these previous results by analyzing the complete pattern of DNA methylation by performing a genome wide bisulphyte sequencing analysis (GWBS) in a control sample, one LRRK2 mutation carrier and one sporadic PD patient.","description":"Previous studies identified epigenetic changes in induced pluripotent stem cells derived dopaminergic neurons (iPSC-Dan) from Parkinson’s disease (PD) patient harboring LRRK2 mutations and in sporadic PD cases without no causative mutation identified wide methylation changes by using the Infinium Human Methylation 450K BeadChip Kit (Illumina). Here, we extend these previous results by analyzing the complete pattern of DNA methylation by performing a genome wide bisulphyte sequencing analysis (GWBS) in a control sample, one LRRK2 mutation carrier and one sporadic PD patient.By using this technique we found a high methylation correlation of the CpG included in our previous Infinium Human Methylation 450K analysis (Fernandez-Santiago., et al., 2015) with data from this study. More specifically, we compared the DMCs found previously in sPD and L2PD by using the 450K array and in a higher number of samples, with our WGBS data. A high overlap were observed between the initial study and the actual data, finding for all combined PD 2089 DMCs in the array and 1911 in WGBS, for sPD 2512 in the array and 2281 in WGBS, and for L2PD 1161 in the previous array and 1116 in WGBS. In addition, we found an overall wide genome hypermethylation in both PD patients compared to the control.","abstract":"Previous studies identified epigenetic changes in induced pluripotent stem cells derived dopaminergic neurons (iPSC-Dan) from Parkinson’s disease (PD) patient harboring LRRK2 mutations and in sporadic PD cases without no causative mutation identified wide methylation changes by using the Infinium Human Methylation 450K BeadChip Kit (Illumina). Here, we extend these previous results by analyzing the complete pattern of DNA methylation by performing a genome wide bisulphyte sequencing analysis (GWBS) in a control sample, one LRRK2 mutation carrier and one sporadic PD patient.By using this technique we found a high methylation correlation of the CpG included in our previous Infinium Human Methylation 450K analysis (Fernandez-Santiago., et al., 2015) with data from this study. More specifically, we compared the DMCs found previously in sPD and L2PD by using the 450K array and in a higher number of samples, with our WGBS data. A high overlap were observed between the initial study and the actual data, finding for all combined PD 2089 DMCs in the array and 1911 in WGBS, for sPD 2512 in the array and 2281 in WGBS, and for L2PD 1161 in the previous array and 1116 in WGBS. In addition, we found an overall wide genome hypermethylation in both PD patients compared to the control.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002714","title":"Keratinocyte_CRISPR_screens","description":"Immortalised HaCaT keratinocytes were transduced with Cas9 and the CRISPR-KO v1.1 genome-wide gRNA library. The gRNA library was prepared from genomic DNA isolated 14 days post library transduction. gRNA representation will be compared to the original CRISPR-KO v1.1 library to reveal genes essential for HaCaT survival and growth.","abstract":"Genome-wide CRISPR/Cas9 screens will be used to identify genes involved in keratinocyte growth, differentiation and inflammation. For essential gene screens, gRNA representation will be compared between cultures at 14 days post-transduction and the original library. For additional screens, gRNA library expressing keratinocytes will FACS-sorted based on the expression of various differentiation or inflammatory markers following relevant differentiation protocols of inflammatory stimuli. gRNA representation between marker positive and negative populations will reveal genes required for the relevant biological process/response.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-02T12:04:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002715","title":"FCA_ImmunoP","description":"Aim of this study is to build a single-cell resolution map of human fetal immune system development. Human fetal cells are processed in HDBR in Newcastle, and converted to single-cell 10x library and sequenced in Sanger.","abstract":"The aim of this study is to build a single-cell resolution map of human fetal immune cell development.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002716","title":"Whole-exome sequencing identifies germline mutations in TP53 and ATRX in a child with genomically aberrant AT/RT and her mother with anaplastic astrocytoma","description":"Brain tumors typically arise sporadically and do not affect several family members simultaneously. In the present study, we describe clinical and genetic data from two patients, a mother and her daughter, with familial brain tumors. Exome sequencing revealed a germline missense mutation in the TP53 and ATRX genes in both cases, and a somatic copy-neutral loss of heterozygosity (LOH) in TP53 in both atypical teratoid/rhabdoid tumor (AT/RT) and astrocytoma tumors. ATRX mutation was associated with the loss of ATRX protein expression. In the astrocytoma case, R132C missense mutation was found in the known hotspot site in isocitrate dehydrogenase 1 (IDH1) and loss of heterozygosity (LOH) was detected in TP53. The mother carried few other somatic alterations, suggesting that the IDH1 mutation and LOH in TP53 were sufficient to drive tumor development. The genome in the AT/RT tumor was atypically aneuploid: most chromosomes had experienced copy-neutral LOH or whole chromosome gains. Only chromosome 18 had normal diploid status. INI1/hSNF5/SMARCB1 was homozygously deleted in the AT/RT tumor. This report provides further information about tumor development in a predisposed genetic background, and describes two special Li-Fraumeni cases with a familial brain tumor.","abstract":"Brain tumors typically arise sporadically and do not affect several family members simultaneously. In the present study, we describe clinical and genetic data from two patients, a mother and her daughter, with familial brain tumors. Exome sequencing revealed a germline missense mutation in the TP53 and ATRX genes in both cases, and a somatic copy-neutral loss of heterozygosity (LOH) in TP53 in both atypical teratoid/rhabdoid tumor (AT/RT) and astrocytoma tumors. ATRX mutation was associated with the loss of ATRX protein expression. In the astrocytoma case, R132C missense mutation was found in the known hotspot site in isocitrate dehydrogenase 1 (IDH1) and loss of heterozygosity (LOH) was detected in TP53. The mother carried few other somatic alterations, suggesting that the IDH1 mutation and LOH in TP53 were sufficient to drive tumor development. The genome in the AT/RT tumor was atypically aneuploid: most chromosomes had experienced copy-neutral LOH or whole chromosome gains. Only chromosome 18 had normal diploid status. INI1/hSNF5/SMARCB1 was homozygously deleted in the AT/RT tumor. This report provides further information about tumor development in a predisposed genetic background, and describes two special Li-Fraumeni cases with a familial brain tumor.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002717","title":"Defining the metastasome in colorectal cancer: Implications for hypotheses on metastasis evolution and personalized therapy (HIPO-032)","description":"Personalized cancer therapy aims at individual genetic changes characterizing primary cancers. Still, however, metastasis is the major clinically unmet problem, also due to an incomplete understanding of its molecular evolution.This study is the first to define the metastasis-specific whole genome landscape of human colorectal primary vs. matched metastatic lesions.Protein coding, ncRNA genes and 3’UTRs harbored about a third each of single nucleotide variations (SNVs)/indels, 19% of them being metastasis-specific. We found novel mutational hills among ncRNAs and 3’UTRs, copy number changes able to explain changes in microRNA expression in metastases, and novel metastasis-specific mutations in the 3’UTRs on important cancer signalling genes. Some metastatic lesions showed targetable mutations not detected in the primaries. Analysis of mutual exclusivity patterns supported a model that has progressive alterations in important colorectal cancer genes and revealed new partners. Metastatic lesions were enriched in SNVs, specific structural variations, and alterations in genes affecting cell adhesion and extracellular matrix interaction.Furthermore, a hepatic stellate activation cascade was enriched in metastases, suggesting genetic programs for site-specific colonization. Allele frequency distribution and mutational signature analysis suggests a common ancestor clone to both the primary tumor and the metastasis, with additional mutagenesis ongoing in both sites independently. Taken together, our results significantly add to hypothesis generation on metastasis evolution, and suggest novel metastasis-specific genomic changes which would be missed by current personalized therapy concepts.  (HIPO-032)","abstract":"Personalized cancer therapy aims at individual genetic changes characterizing primary cancers. Still, however, metastasis is the major clinically unmet problem, also due to an incomplete understanding of its molecular evolution.This study is the first to define the metastasis-specific whole genome landscape of human colorectal primary vs. matched metastatic lesions.Protein coding, ncRNA genes and 3’UTRs harbored about a third each of single nucleotide variations (SNVs)/indels, 19% of them being metastasis-specific. We found novel mutational hills among ncRNAs and 3’UTRs, copy number changes able to explain changes in microRNA expression in metastases, and novel metastasis-specific mutations in the 3’UTRs on important cancer signalling genes. Some metastatic lesions showed targetable mutations not detected in the primaries. Analysis of mutual exclusivity patterns supported a model that has progressive alterations in important colorectal cancer genes and revealed new partners. Metastatic lesions were enriched in SNVs, specific structural variations, and alterations in genes affecting cell adhesion and extracellular matrix interaction.Furthermore, a hepatic stellate activation cascade was enriched in metastases, suggesting genetic programs for site-specific colonization. Allele frequency distribution and mutational signature analysis suggests a common ancestor clone to both the primary tumor and the metastasis, with additional mutagenesis ongoing in both sites independently. Taken together, our results significantly add to hypothesis generation on metastasis evolution, and suggest novel metastasis-specific genomic changes which would be missed by current personalized therapy concepts.  (HIPO-032)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-03T15:22:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002718","title":"We performed whole-exome sequencing and whole epigenome sequencing (RRBS) of samples collected from different time points during radiotherapy from thirty-four ESCC patients. We compared the genetic and epigenetic features of the different time biopsy samples to reveal the changes in ESCC received radiotherapy.","description":"We performed whole-exome sequencing and whole epigenome sequencing (RRBS) of samples collected from different time points during radiotherapy from thirty-four ESCC patients. We compared the genetic and epigenetic features of the different time biopsy samples to reveal the changes in ESCC received radiotherapy.","abstract":"We performed whole-exome sequencing and whole epigenome sequencing (RRBS) of samples collected from different time points during radiotherapy from thirty-four ESCC patients. We compared the genetic and epigenetic features of the different time biopsy samples to reveal the changes in ESCC received radiotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-14T01:00:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002719","title":"We performed whole-exome sequencing and whole epigenome sequencing (RRBS) of samples collected from different time points during radiotherapy from thirty-four ESCC patients. We compared the genetic and epigenetic features of the different time biopsy samples to reveal the changes in ESCC received radiotherapy.","description":"We performed whole-exome sequencing and whole epigenome sequencing (RRBS) of samples collected from different time points during radiotherapy from thirty-four ESCC patients. We compared the genetic and epigenetic features of the different time biopsy samples to reveal the changes in ESCC received radiotherapy.","abstract":"We performed whole-exome sequencing and whole epigenome sequencing (RRBS) of samples collected from different time points during radiotherapy from thirty-four ESCC patients. We compared the genetic and epigenetic features of the different time biopsy samples to reveal the changes in ESCC received radiotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-06T06:14:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002720","title":"Defective Homologous Recombination DNA Repair as Therapeutic Target in Advanced-Stage Chordoma (HIPO_021)","description":"HIPO project: HIPO_021\nImportance: Chordomas are rare tumors of the axial skeleton and skull base with few therapeutic options and no clinically validated molecular drug targets. The value of comprehensive genomic analyses for guiding medical therapy of patients with advanced-stage chordoma is unknown.Objective: To identify therapeutically tractable genetic lesions in a cohort of chordoma patients within a genomics-guided precision oncology program and to document the outcome of individualized, molecularly targeted chordoma therapy.Design, Setting, and Participants: We performed whole-exome sequencing of tumor and matched germline control samples from seven patients with locally advanced or metastatic chordoma who were enrolled in a cross-institutional molecular stratification registry trial for younger adults with advanced-stage cancer across all histologies and patients with rare tumors. All patients were heavily pretreated and had progressive disease prior to molecular analysis.Interventions: Individualized medical therapy was administered according to the patients’ molecular profiles.Main Outcomes and Measures: Candidate therapeutic targets identified by whole-exome sequencing and response to genotype-directed therapy.Results: All patients harbored alterations of two or more genes known to be involved in DNA repair via homologous recombination (HR), including heterozygous deletions of ERCC6, FANC family members, RAD51L (n = 6), BRCA2 (n = 5), ATR, CHEK2, RAD18, RAD51B, and XRCC3 (n = 4); inactivating PTEN mutations coupled with loss of heterozygosity (n = 2); and pathogenic germline variants in BRCA2 (n = 1), NBN (n = 1), and CHEK2 (n = 1) that were accompanied by somatic deletion of the corresponding wild-type alleles. Consistently, a mutational signature associated with defective HR was enriched in all samples and co-occurred with extensive genomic instability, as evidenced by HR deficiency scores and high numbers of large-scale state transitions. These results prompted off-label treatment with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib in a patient whose tumor was refractory to irradiation and systemic treatment with imatinib, which led to a prolonged response and substantial clinical improvement.Conclusions and Relevance: Advanced-stage chordomas are frequently characterized by genomic imprints of defective HR DNA repair. HR deficiency represents a new therapeutic opportunity in this intractable disease through repositioning of PARP inhibitors that warrants further exploration in clinical trials.","abstract":"HIPO project: HIPO_021\nImportance: Chordomas are rare tumors of the axial skeleton and skull base with few therapeutic options and no clinically validated molecular drug targets. The value of comprehensive genomic analyses for guiding medical therapy of patients with advanced-stage chordoma is unknown.Objective: To identify therapeutically tractable genetic lesions in a cohort of chordoma patients within a genomics-guided precision oncology program and to document the outcome of individualized, molecularly targeted chordoma therapy.Design, Setting, and Participants: We performed whole-exome sequencing of tumor and matched germline control samples from seven patients with locally advanced or metastatic chordoma who were enrolled in a cross-institutional molecular stratification registry trial for younger adults with advanced-stage cancer across all histologies and patients with rare tumors. All patients were heavily pretreated and had progressive disease prior to molecular analysis.Interventions: Individualized medical therapy was administered according to the patients’ molecular profiles.Main Outcomes and Measures: Candidate therapeutic targets identified by whole-exome sequencing and response to genotype-directed therapy.Results: All patients harbored alterations of two or more genes known to be involved in DNA repair via homologous recombination (HR), including heterozygous deletions of ERCC6, FANC family members, RAD51L (n = 6), BRCA2 (n = 5), ATR, CHEK2, RAD18, RAD51B, and XRCC3 (n = 4); inactivating PTEN mutations coupled with loss of heterozygosity (n = 2); and pathogenic germline variants in BRCA2 (n = 1), NBN (n = 1), and CHEK2 (n = 1) that were accompanied by somatic deletion of the corresponding wild-type alleles. Consistently, a mutational signature associated with defective HR was enriched in all samples and co-occurred with extensive genomic instability, as evidenced by HR deficiency scores and high numbers of large-scale state transitions. These results prompted off-label treatment with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib in a patient whose tumor was refractory to irradiation and systemic treatment with imatinib, which led to a prolonged response and substantial clinical improvement.Conclusions and Relevance: Advanced-stage chordomas are frequently characterized by genomic imprints of defective HR DNA repair. HR deficiency represents a new therapeutic opportunity in this intractable disease through repositioning of PARP inhibitors that warrants further exploration in clinical trials.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-06T11:29:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002721","title":"Characterization of a human iPSC-derived islet differentiation model","description":"To explore the contribution of islet development to T2D pathogenesis, we characterised the transcriptomes of 3 human iPSC lines (from independent donors) differentiated along the islet development lineage. Whole transcriptome RNA-seq was performed at 7 developmental stages: definitive endoderm, primitive gut tube, posterior foregut (PF), pancreatic endoderm, endocrine progenitors, endocrine-like cells, and beta-like cells (BLC). Differentially-expressed (ΔExp) genes were assigned to the stage in which they were most upregulated (versus baseline iPSC profile), and used to assess the enrichment of T2D GWAS genes, as well as to predict the upstream transcription factors at each developmental stage.We found 9409 ΔExp genes across all stages, including known markers of islet development (NEUROG3, INS). Genes ΔExp in the most-differentiated (BLC) stage were significantly enriched for genes within the 99% credible sets of T2D GWAS loci. Despite this enrichment in BLC only, over 70% of genes mapping within the credible sets were ΔExp before this stage, highlighting the relevance of key T2D GWAS genes in islet development: e.g. expression of TCF7L2 peaked during the PF stage (log2FC=1.2; q=8.5×10-10). REST and LMNA are also highlighted by the analyses as having a potential function in islet development, considering their pattern of expression and those of the genes they regulate. Transcriptomic signatures derived from this iPSC differentiation model highlight T2D-associated GWAS loci, monogenic diabetes genes and potential master regulators of gene networks with plausible function in islet development. All these provide clues for developmental mechanisms contributing to T2D diabetes pathology.","abstract":"To explore the contribution of islet development to T2D pathogenesis, we characterised the transcriptomes of 3 human iPSC lines (from independent donors) differentiated along the islet development lineage. Whole transcriptome RNA-seq was performed at 7 developmental stages: definitive endoderm, primitive gut tube, posterior foregut (PF), pancreatic endoderm, endocrine progenitors, endocrine-like cells, and beta-like cells (BLC). Differentially-expressed (ΔExp) genes were assigned to the stage in which they were most upregulated (versus baseline iPSC profile), and used to assess the enrichment of T2D GWAS genes, as well as to predict the upstream transcription factors at each developmental stage.We found 9409 ΔExp genes across all stages, including known markers of islet development (NEUROG3, INS). Genes ΔExp in the most-differentiated (BLC) stage were significantly enriched for genes within the 99% credible sets of T2D GWAS loci. Despite this enrichment in BLC only, over 70% of genes mapping within the credible sets were ΔExp before this stage, highlighting the relevance of key T2D GWAS genes in islet development: e.g. expression of TCF7L2 peaked during the PF stage (log2FC=1.2; q=8.5×10-10). REST and LMNA are also highlighted by the analyses as having a potential function in islet development, considering their pattern of expression and those of the genes they regulate. Transcriptomic signatures derived from this iPSC differentiation model highlight T2D-associated GWAS loci, monogenic diabetes genes and potential master regulators of gene networks with plausible function in islet development. All these provide clues for developmental mechanisms contributing to T2D diabetes pathology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-06T11:44:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002722","title":"To understand comprehensive combinations of molecular alterations and seek for potential therapeutic targets/pathways in virus-associated HCC, we have conducted a whole exome sequencing of 503 HCC cases.","description":"Diverse epidemiological factors are associated with hepatocellular carcinoma (HCC) prevalence in different populations. However, the global landscape of the genetic changes in HCC genomes underpinning different epidemiological and ancestral backgrounds still remains uncharted. Here a collection of data from 503 liver cancer genomes from different populations uncovered 30 candidate driver genes and 11 core pathway modules. Furthermore, a collaboration of two large-scale cancer genome projects comparatively analyzed the trans-ancestry substitution signatures in 608 liver cancer cases and identified unique mutational signatures that predominantly contribute to Asian cases. This work elucidates previously unexplored ancestry-associated mutational processes in HCC development. A combination of hotspot TERT promoter mutation, TERT focal amplification and viral genome integration occurs in more than 68% of cases, implicating TERT as a central and ancestry-independent node of hepatocarcinogenesis. Newly identified alterations in genes encoding metabolic enzymes, chromatin remodelers and a high proportion of mTOR pathway activations offer potential therapeutic and diagnostic opportunities.","abstract":"Diverse epidemiological factors are associated with hepatocellular carcinoma (HCC) prevalence in different populations. However, the global landscape of the genetic changes in HCC genomes underpinning different epidemiological and ancestral backgrounds still remains uncharted. Here a collection of data from 503 liver cancer genomes from different populations uncovered 30 candidate driver genes and 11 core pathway modules. Furthermore, a collaboration of two large-scale cancer genome projects comparatively analyzed the trans-ancestry substitution signatures in 608 liver cancer cases and identified unique mutational signatures that predominantly contribute to Asian cases. This work elucidates previously unexplored ancestry-associated mutational processes in HCC development. A combination of hotspot TERT promoter mutation, TERT focal amplification and viral genome integration occurs in more than 68% of cases, implicating TERT as a central and ancestry-independent node of hepatocarcinogenesis. Newly identified alterations in genes encoding metabolic enzymes, chromatin remodelers and a high proportion of mTOR pathway activations offer potential therapeutic and diagnostic opportunities.","study_type":"Other","pubmed_ids":[25362482],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001002723","title":"Genetic_Overlap_between_Metabolic_and_Psychiatric_disease","description":"The Genetic Overlap between Metabolic and Psychiatric Diseases (GOMAP) study comprises samples from four patient groups: 964 schizophrenia samples, 921 type 2 diabetes patients, 582 patients with comorbid schizophrenia and type 2 diabetes and 280 samples with another psychiatric diagnosis.","abstract":"Schizophrenia patients are at an increased risk of developing type 2 diabetes compared ot the general population. There are several possible explanaitons for this epidemiological link, such as the side effects of antipsychotic medication, shared lifestyle factors and common genetic predisposition. The GOMAP study aims to elucidate to what extent shared genetics contributes to the observed comorbidity between these two disorders using a range of methods including case-case genomide association studies and risk score analyses. The availability of in-depth phenotypic information along with the presence of the comorbid patient group enable detailed analyses of the genetic overlap between schizophrenia and type 2 diabetes.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-09T09:25:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002724","title":"Angiopredict: predicting response for bevacizumab treatment","description":"In ANGIOPREDICT, academic cancer biologists and industry-based biotechnology researchers worked with clinicians to identify biomarkers to predict whether individual metastatic colorectal cancer patients will respond positively to bevacizumab containing therapy. In this retrospective study, copy number profiles were determined  using whole genome shallow sequencing, and progression free survival and treatment data was collected.","abstract":"In ANGIOPREDICT, academic cancer biologists and industry-based biotechnology researchers worked with clinicians to identify biomarkers to predict whether individual metastatic colorectal cancer patients will respond positively to bevacizumab containing therapy. In this retrospective study, copy number profiles were determined  using whole genome shallow sequencing, and progression free survival and treatment data was collected.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-09T09:43:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002725","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__Oesophageal_squamous_cell_carcinoma","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute (Illumina HiSeqX, 40X and 20X depth respectively). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \n\nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute (Illumina HiSeqX, 40X and 20X depth respectively). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \n\nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-09T16:36:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002726","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__pancreas","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute (Illumina HiSeqX, 40X and 20X depth respectively). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \n\nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute (Illumina HiSeqX, 40X and 20X depth respectively). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \n\nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-09T16:41:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002727","title":"Exome and RNA sequencing of Greenlanders","description":"This study contains whole exome sequence of 27 Greenlanders and deep RNA sequencing of 17 Greenlanders","abstract":"This study contains whole exome sequence of 27 Greenlanders and deep RNA sequencing of 17 Greenlanders","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-13T10:03:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002728","title":"CancerDetector: Ultrasensitive and Non-Invasive Cancer Detection at the Resolution of Individual Reads using Cell-free DNA Methylation Sequencing Data","description":"The detection of tumor-derived cell-free DNA in plasma is one of the most promising directions in cancer diagnosis. The major challenge in such approach is how to identify the tiny amount of tumor DNAs out of total cell-free DNAs in blood. Here we propose an ultrasensitive cancer detection method, termed “CancerDetector”, using the DNA methylation profiles of cell-free DNAs. The key of our method is to probabilistically model the joint methylation patterns of multiple adjacent CpG sites on an individual sequencing read, in order to exploit the pervasive nature of DNA methylation for signal amplification. Therefore, CancerDetector can sensitively identify a trace amount of tumor cfDNAs in plasma, at the level of individual reads. We evaluated CancerDetector on the simulated data, and showed a high concordance of the predicted and true tumor burden. Testing CancerDetector on real plasma data demonstrated its high sensitivity and specificity in detecting tumor DNAs. In addition, the predicted tumor burden showed great consistency with tumor size and survival outcome. Note that all of those testing were performed on sequencing data at low to medium coverage (1X to 10X). Therefore, CancerDetector holds the great potential to detect cancer early and cost-effectively.","abstract":"The detection of tumor-derived cell-free DNA in plasma is one of the most promising directions in cancer diagnosis. The major challenge in such approach is how to identify the tiny amount of tumor DNAs out of total cell-free DNAs in blood. Here we propose an ultrasensitive cancer detection method, termed “CancerDetector”, using the DNA methylation profiles of cell-free DNAs. The key of our method is to probabilistically model the joint methylation patterns of multiple adjacent CpG sites on an individual sequencing read, in order to exploit the pervasive nature of DNA methylation for signal amplification. Therefore, CancerDetector can sensitively identify a trace amount of tumor cfDNAs in plasma, at the level of individual reads. We evaluated CancerDetector on the simulated data, and showed a high concordance of the predicted and true tumor burden. Testing CancerDetector on real plasma data demonstrated its high sensitivity and specificity in detecting tumor DNAs. In addition, the predicted tumor burden showed great consistency with tumor size and survival outcome. Note that all of those testing were performed on sequencing data at low to medium coverage (1X to 10X). Therefore, CancerDetector holds the great potential to detect cancer early and cost-effectively.","study_type":"Other","pubmed_ids":[29897492],"external_links":null,"is_released":true,"released_date":"2017-11-15T17:52:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002729","title":"We describe a method to culture organoids from adult human kidney tissue and describe applications for the culture system.","description":"Adult Stem Cell (ASC)-derived organoids are 3D epithelial structures that recapitulate essential aspects of their organ of origin. We have developed conditions for the long-term growth of primary kidney epithelial organoids. Cultures can be established from mouse and human kidney tissue, as well as from urine and can be expanded for at least 20 passages (&gt; 6 months). Chromosome numbers remain normal. Human organoids represent proximal as well as distal nephron segments, as evidenced by gene expression, immunofluorescence and tubular functional analyses. BK virus infection of organoids recapitulates in vivo phenomena. Organoids can be established from Wilms nephroblastoma. Kidney organoids from Cystic Fibrosis (CF) patient’s urine allowed ex vivo assessment of treatment efficacy. Finally, organoids cultured on microfluidic organ-on-a-chip plates adopt a tubular conformation and display active transport function. Adult kidney-derived organoids allow studies of hereditary, infectious and malignant kidney disease in a personalized fashion.","abstract":"Adult Stem Cell (ASC)-derived organoids are 3D epithelial structures that recapitulate essential aspects of their organ of origin. We have developed conditions for the long-term growth of primary kidney epithelial organoids. Cultures can be established from mouse and human kidney tissue, as well as from urine and can be expanded for at least 20 passages (&gt; 6 months). Chromosome numbers remain normal. Human organoids represent proximal as well as distal nephron segments, as evidenced by gene expression, immunofluorescence and tubular functional analyses. BK virus infection of organoids recapitulates in vivo phenomena. Organoids can be established from Wilms nephroblastoma. Kidney organoids from Cystic Fibrosis (CF) patient’s urine allowed ex vivo assessment of treatment efficacy. Finally, organoids cultured on microfluidic organ-on-a-chip plates adopt a tubular conformation and display active transport function. Adult kidney-derived organoids allow studies of hereditary, infectious and malignant kidney disease in a personalized fashion.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-16T09:05:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002730","title":"Brain transcriptome of hereditary cerebral haemorrhage with amyloidosis–Dutch type (HCHWA-D)","description":"HCHWA-D is an early onset hereditary form of Cerebral Amyloid Angiopathy (CAA) caused by a point mutation resulting in an amino acid change (NP_000475.1:p.Glu693Gln) in the Amyloid Precursor Protein (APP). Post-mortem brain tissue (9 patients and 9 age-related controls; frontal and occipital cortex) was used for next generation sequencing of RNA (RNA-Seq with ribosomal RNA depletion).","abstract":"HCHWA-D is an early onset hereditary form of Cerebral Amyloid Angiopathy (CAA) caused by a point mutation resulting in an amino acid change (NP_000475.1:p.Glu693Gln) in the Amyloid Precursor Protein (APP). Post-mortem brain tissue (9 patients and 9 age-related controls; frontal and occipital cortex) was used for next generation sequencing of RNA (RNA-Seq with ribosomal RNA depletion).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-16T14:27:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002731","title":"Himalayan_population_genetic_study","description":"We genotyped 770 individuals belonging to 49 populations from Nepal, Bhutan, North India or Tibet at over 500,000 SNPs genomewide to investigate the demographic history of the region and the genetic adaptations to the harsh environment. \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We genotyped 770 individuals belonging to 49 populations from Nepal, Bhutan, North India or Tibet at over 500,000 SNPs genomewide to investigate the demographic history of the region and the genetic adaptations to the harsh environment.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-16T14:54:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002732","title":"Study of multifocal HCC in an inactive HBV carrier","description":"We studied the inactive HBV carrier with four tumors (T1-T4) and two tumor thrombus (HVTT and PVTT) in his liver to investigate the origin model of multifocal HCC. We performed the whole genome sequencing (WGS) and virus captured sequencing (VCS) in all tissues including four adjacent controls (N1-N4). We further applied virus capture sequencing on 264 singles cells selected from the six cancer tissues (T1-T4, HVTT and PVTT). HBV variants and integrations, and mutations on cancer genomes in multiple tumors were analyzed.","abstract":"We studied the inactive HBV carrier with four tumors (T1-T4) and two tumor thrombus (HVTT and PVTT) in his liver to investigate the origin model of multifocal HCC. We performed the whole genome sequencing (WGS) and virus captured sequencing (VCS) in all tissues including four adjacent controls (N1-N4). We further applied virus capture sequencing on 264 singles cells selected from the six cancer tissues (T1-T4, HVTT and PVTT). HBV variants and integrations, and mutations on cancer genomes in multiple tumors were analyzed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002733","title":"Targeted next-generation sequencing of 13 chordoid gliomas of the third ventricle","description":null,"abstract":"Chordoid glioma is a rare brain tumor thought to arise from specialized ependymal cells of the lamina terminalis along the anterior wall of the third ventricle.  We performed targeted next-generation sequencing of approximately 500 cancer-associated genes on a cohort of 13 chordoid gliomas and identified a recurrent D463H missense mutation in the PRKCA gene in all tumors, which localizes in the kinase domain of the encoded protein kinase C alpha (PKCa).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-22T07:49:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002734","title":"CellGen_Single_cell_transcriptomic_analysis_of_effector_cytokine_secreting_immune_cells_in_human_tumors","description":"The aim of this project is to unravel for the first time the contribution of Innate Lymphoid Cells to the polarization of the TME, using a single cell transcriptomic approach. We will isolate individual ILCs and tumor-specific CD4 T cells (using pMHC class II multimers) from the tumor tissues, healthy tissues and peripheral blood of cancer patients (e.g. bladder and prostate cancer) at different disease stages, and dissect their transcriptional landscape.\nIn a successive step we will decode the most relevant altered pathways using well-defined in vitro system and genetic-based in vivo assays.     \n This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This work will provide the first characterization of active transcriptional regulatory networks in human ILC and CD4 Th cells in cancer, at the single cell level. In detail, we will i) explore the gene expression relationships between innate and adaptive cell types, as well as among ILCs and Th subsets, ii) identify “unique” and “shared” transcripts between ILC and their Th cell counterparts, iii) screen for “tumor specific” signatures, by comparing results obtained in patients with our and published work performed in healthy donors/reference samples and iv) define transcriptional alterations in epigenetic modulators. Overall, my hypothesis is that by dissecting and manipulating transcriptomic modules of innate and adaptive cytokine secreting cells in the tumor microenvironment we will switch them from immunosuppressive Type2- to proinflammatory Type1-polarized cells. Thus, we will transform the overall polarization of the tumor niche, energize anti-tumor immunity and promote tumor eradication.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002735","title":"Single_cell_sequencing_of_pediatric_arthritis_VDJ___chromium","description":"We performed single cell analysis of cells from blood and synovial fluid of children suffering from unindentified arthritis","abstract":"We performed single cell analysis of cells from blood and synovial fluid of children suffering from unindentified arthritis. With this we aim to obtain better understanding of the disease status of these patients and how they can be treated","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002736","title":"Molecular characterization of endothelial cells under conditions associated with hematopoietic niche formation in humans","description":"Using a combinatory approach of cell purification and transcriptomics, we identify a subset of endoglin-expressing endothelial cells enriched in human bone marrow during fetal ontogeny and regeneration after chemotherapeutic injury. Comprehensive transcriptional characterization by massive parallel RNA sequencing of these cells revealed a remarkable phenotypic and molecular similarity to murine H endothelium as well as activation of pathways and angiocrine factors implicated in hematopoiesis, osteogenesis and angiogenesis.","abstract":"Using a combinatory approach of cell purification and transcriptomics, we identify a subset of endoglin-expressing endothelial cells enriched in human bone marrow during fetal ontogeny and regeneration after chemotherapeutic injury. Comprehensive transcriptional characterization by massive parallel RNA sequencing of these cells revealed a remarkable phenotypic and molecular similarity to murine H endothelium as well as activation of pathways and angiocrine factors implicated in hematopoiesis, osteogenesis and angiogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-22T14:19:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002737","title":"Evolutionary analysis of primary tumors and metastatic lesions from 20 breast cancer patients (99 samples in total) using exome sequencing data.","description":"Metastatic breast cancers are still incurable. Characterizing their evolutionary landscape including the role of metastatic axillary lymph nodes to seed distant organ metastasis can provide rational basis for effective treatments. Here, we describe the genomic analyses of the primary tumors and metastatic lesions from 20 breast cancer patients (99 samples). Our evolutionary analyses revealed diverse spreading and seeding patterns governing tumor progression. Although linear evolution to successive metastatic sites was common, parallel evolution from the primary tumor to multiple distant sites was also evident. Metastatic spreading was frequently coupled with polyclonal seeding, where multiple metastatic subclones originated from primary tumor and/or other distant metastases.  Synchronous axillary lymph node metastasis, a well-established prognosticator of breast cancer, was not involved in seeding distant metastasis, suggesting haematogenous route for cancer dissemination. Clonal evolution coincided frequently with emerging driver alterations and evolving mutational processes, notably a significant increase in apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) associated mutagenesis. Our data provide the first genomic evidence regarding the role of axillary lymph node metastasis in seeding distant organ metastasis and elucidates the evolving mutational landscape during cancer progression.","abstract":"Metastatic breast cancers are still incurable. Characterizing their evolutionary landscape including the role of metastatic axillary lymph nodes to seed distant organ metastasis can provide rational basis for effective treatments. Here, we describe the genomic analyses of the primary tumors and metastatic lesions from 20 breast cancer patients (99 samples). Our evolutionary analyses revealed diverse spreading and seeding patterns governing tumor progression. Although linear evolution to successive metastatic sites was common, parallel evolution from the primary tumor to multiple distant sites was also evident. Metastatic spreading was frequently coupled with polyclonal seeding, where multiple metastatic subclones originated from primary tumor and/or other distant metastases.  Synchronous axillary lymph node metastasis, a well-established prognosticator of breast cancer, was not involved in seeding distant metastasis, suggesting haematogenous route for cancer dissemination. Clonal evolution coincided frequently with emerging driver alterations and evolving mutational processes, notably a significant increase in apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) associated mutagenesis. Our data provide the first genomic evidence regarding the role of axillary lymph node metastasis in seeding distant organ metastasis and elucidates the evolving mutational landscape during cancer progression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-23T12:21:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002738","title":"X chromosomal genetic variants are associated with childhood obesity","description":"Current genetic association studies are usually focused on autosomal variants only, and the sex chromosomes are often neglected. In recent years, a number of statistical techniques and strategies have been widely described making much easier overcoming X-chromosome technical hurdles and including this region within genetic studies. Tenomodulin (TNMD) is a Xq22 chromosome anti angiogenic locus which has been recently linked to different obesity-related phenotypes. These results have not been replicated to date. Given these facts, we have conducted a genetic association analysis in Spanish children population including seven TNMD SNPs as potential candidate markers for obesity and metabolic dysfunctions. Additionally genotypes for another locus located in the X chromosome, the SLC6A14, have been included in the dataset.\n\nA total of 915 DNA samples from 258 normal weight, 177 overweight and 480 obese Spanish children (438 males, 477\nfemales) were genotyped for seven TNMD SNPs and one SLC6A14 SNP. Associations with anthropometric measurements and glucose metabolism were\ninvestigated.","abstract":"Current genetic association studies are usually focused on autosomal variants only, and the sex chromosomes are often neglected. In recent years, a number of statistical techniques and strategies have been widely described making much easier overcoming X-chromosome technical hurdles and including this region within genetic studies. Tenomodulin (TNMD) is a Xq22 chromosome anti angiogenic locus which has been recently linked to different obesity-related phenotypes. These results have not been replicated to date. Given these facts, we have conducted a genetic association analysis in Spanish children population including seven TNMD SNPs as potential candidate markers for obesity and metabolic dysfunctions. Additionally genotypes for another locus located in the X chromosome, the SLC6A14, have been included in the dataset.\n\nA total of 915 DNA samples from 258 normal weight, 177 overweight and 480 obese Spanish children (438 males, 477\nfemales) were genotyped for seven TNMD SNPs and one SLC6A14 SNP. Associations with anthropometric measurements and glucose metabolism were\ninvestigated.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-26T18:45:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002739","title":"CRISPR_screen_for_cancer_cell_sensitivity_resistance_to_NK_cell_killing","description":"Looking for resistance or sensitivity to NK cell mediated killing in cell lines through CRISPR KO enrichment or dropout.","abstract":"Looking for resistance or sensitivity to NK cell mediated killing in cell lines through CRISPR KO enrichment or dropout.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002740","title":"Targeted Gene Panel for 171 PTCLs","description":"Mature T-cell lymphomas, including peripheral T-cell lymphoma (PTCL) and extranodal NK/T-cell lymphoma (NKTL), represent a heterogeneous group of non-Hodgkin lymphomas with dismal outcomes and limited treatment options. To determine the extent of involvement of the JAK/STAT pathway in this malignancy, we performed targeted capture sequencing of 188 genes in this pathway in 171 PTCL and NKTL cases. A total of 272 nonsynonymous somatic mutations in 101 genes were identified in 73% of the samples, including 258 single-nucleotide variants and 14 insertions or deletions. Recurrent mutations were most frequently located in STAT3 and TP53 (15%), followed by JAK3 and JAK1 (6%) and SOCS1 (4%). A high prevalence of STAT3 mutation (21%) was observed specifically in NKTL. Novel STAT3 mutations (p.D427H, E616G, p.E616K, and p.E696K) were shown to increase STAT3 phosphorylation and transcriptional activity of STAT3 in the absence of cytokine, in which p.E616K induced programmed cell death-ligand 1 (PD-L1) expression by robust binding of activated STAT3 to the PD-L1 gene promoter. Consistent with these findings, PD-L1 was overexpressed in NKTL cell lines harboring hotspot STAT3 mutations, and similar findings were observed by the overexpression of p.E616K and p.E616G in the STAT3 wild-type NKTL cell line. Conversely, STAT3 silencing and inhibition decreased PD-L1 expression in STAT3 mutant NKTL cell lines. In NKTL tumors, STAT3 activation correlated significantly with PD-L1 expression. We demonstrated that STAT3 activation confers high PD-L1 expression, which may promote tumor immune evasion. The combination of PD-1/PD-L1 antibodies and STAT3 inhibitors might be a promising therapeutic approach for NKTL, and possibly PTCL.","abstract":"Mature T-cell lymphomas, including peripheral T-cell lymphoma (PTCL) and extranodal NK/T-cell lymphoma (NKTL), represent a heterogeneous group of non-Hodgkin lymphomas with dismal outcomes and limited treatment options. To determine the extent of involvement of the JAK/STAT pathway in this malignancy, we performed targeted capture sequencing of 188 genes in this pathway in 171 PTCL and NKTL cases. A total of 272 nonsynonymous somatic mutations in 101 genes were identified in 73% of the samples, including 258 single-nucleotide variants and 14 insertions or deletions. Recurrent mutations were most frequently located in STAT3 and TP53 (15%), followed by JAK3 and JAK1 (6%) and SOCS1 (4%). A high prevalence of STAT3 mutation (21%) was observed specifically in NKTL. Novel STAT3 mutations (p.D427H, E616G, p.E616K, and p.E696K) were shown to increase STAT3 phosphorylation and transcriptional activity of STAT3 in the absence of cytokine, in which p.E616K induced programmed cell death-ligand 1 (PD-L1) expression by robust binding of activated STAT3 to the PD-L1 gene promoter. Consistent with these findings, PD-L1 was overexpressed in NKTL cell lines harboring hotspot STAT3 mutations, and similar findings were observed by the overexpression of p.E616K and p.E616G in the STAT3 wild-type NKTL cell line. Conversely, STAT3 silencing and inhibition decreased PD-L1 expression in STAT3 mutant NKTL cell lines. In NKTL tumors, STAT3 activation correlated significantly with PD-L1 expression. We demonstrated that STAT3 activation confers high PD-L1 expression, which may promote tumor immune evasion. The combination of PD-1/PD-L1 antibodies and STAT3 inhibitors might be a promising therapeutic approach for NKTL, and possibly PTCL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-27T10:01:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002741","title":"<blank>","description":"&lt;abstract&gt;","abstract":"&lt;abstract&gt;","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002742","title":"The_British_Autozygosity_Populations_BioResource","description":"This data set contains whole exome sequences of individuals with self-stated parental relatedness from the East London Genes &amp; Health cohort. Rare frequency functional variants in these healthy individuals will be studied with respect to the genetic health of the participants and loss-of-function analysis of human genes.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This data set contains whole exome sequences of individuals with self-stated parental relatedness from the East London Genes &amp; Health cohort. Rare frequency functional variants in these healthy individuals will be studied with respect to the genetic health of the participants and loss-of-function analysis of human genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-28T10:56:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002743","title":"Aggressive genomic features in clinicallyindolent primary HHV8-negative effusion-based lymphoma","description":"Human herpesvirus 8-negative effusion-based lymphoma (HHV8-negative EBL) is a distinct lymphoma entity related to fluid overload states caused by underlying medical conditions. Due to a phenotypical resemblance with secondary effusion of diffuse large B-cell lymphoma (DLBCL), HHV8-negative EBL is easily misdiagnosed. However, in contrast to DLBCL, HHV8-negative EBL follows a mild clinical course, underpinning the importance to differentiate between the two entities. Only limited molecular data of HHV8-negative EBL has been reported and characteristic genomic patterns are lacking. We performed extensive genomic profiling on 8 HHV8-negative EBL cases. A mean number of 33.6 copy number gains and losses per case were found, with recurrent focal deletions of chromosome 3p14.2 and 6q21 in 6/8 cases, encompassing tumor supressor genes FHIT and PRDM1, respectively. We observed a high rate of mutations across genes frequently involved in DLBCL, including patterns of somatic hypermutation. The most abundant hotspot mutation was found in MYD88L265P (3/8 cases). In addition, 5/8 cases had one or more translocations, involving MYC, BCL2, BCL6, TP63, EXOC2 and KMT2D, with Ig and non-Ig partners. We conclude that HHV8-negative EBL is characterized by genomic features that are commonly found  in more aggressive B-cell lymphomas, but despite this follow an indolent clinical course.","abstract":"Human herpesvirus 8-negative effusion-based lymphoma (HHV8-negative EBL) is a distinct lymphoma entity related to fluid overload states caused by underlying medical conditions. Due to a phenotypical resemblance with secondary effusion of diffuse large B-cell lymphoma (DLBCL), HHV8-negative EBL is easily misdiagnosed. However, in contrast to DLBCL, HHV8-negative EBL follows a mild clinical course, underpinning the importance to differentiate between the two entities. Only limited molecular data of HHV8-negative EBL has been reported and characteristic genomic patterns are lacking. We performed extensive genomic profiling on 8 HHV8-negative EBL cases. A mean number of 33.6 copy number gains and losses per case were found, with recurrent focal deletions of chromosome 3p14.2 and 6q21 in 6/8 cases, encompassing tumor supressor genes FHIT and PRDM1, respectively. We observed a high rate of mutations across genes frequently involved in DLBCL, including patterns of somatic hypermutation. The most abundant hotspot mutation was found in MYD88L265P (3/8 cases). In addition, 5/8 cases had one or more translocations, involving MYC, BCL2, BCL6, TP63, EXOC2 and KMT2D, with Ig and non-Ig partners. We conclude that HHV8-negative EBL is characterized by genomic features that are commonly found  in more aggressive B-cell lymphomas, but despite this follow an indolent clinical course.","study_type":"Other","pubmed_ids":[30510084],"external_links":null,"is_released":true,"released_date":"2017-11-29T10:55:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002744","title":"The molecular basis of T-PLL is an actionable perturbation of TCL1/ATM- and epigenetically instructed damage responses","description":"T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell malignancy. To address its incomplete molecular concept, we integrated large-scale profiling data of alterations in gene expression, allelic copy number (CN), and nucleotide sequences in 111 well-characterized patients. Besides prominent signatures of T-cell activation and prevalent clonal variants, we also identified novel hot-spots for CN variability, fusion molecules, alternative transcripts, and progression-associated dynamics. The overall lesional spectrum of T-PLL is mainly annotated to axes of DNA damage responses, T-cell receptor/cytokine signaling, and histone modulation. We formulate a multi-dimensional model of T-PLL pathogenesis centered around a unique combination of TCL1 overexpression with damaging ATM aberrations as initiating core lesions. The effects imposed by TCL1 cooperate with compromised ATM towards a leukemogenic phenotype of impaired DNA damage processing. Dysfunctional ATM appears inefficient in alleviating elevated redox burdens and telomere attrition and in evoking a p53-dependent apoptotic response to genotoxic insults. As non-genotoxic strategies, synergistic combinations of p53 reactivators and deacetylase inhibitors reinstate such cell death execution.","abstract":"T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell malignancy. To address its incomplete molecular concept, we integrated large-scale profiling data of alterations in gene expression, allelic copy number (CN), and nucleotide sequences in 111 well-characterized patients. Besides prominent signatures of T-cell activation and prevalent clonal variants, we also identified novel hot-spots for CN variability, fusion molecules, alternative transcripts, and progression-associated dynamics. The overall lesional spectrum of T-PLL is mainly annotated to axes of DNA damage responses, T-cell receptor/cytokine signaling, and histone modulation. We formulate a multi-dimensional model of T-PLL pathogenesis centered around a unique combination of TCL1 overexpression with damaging ATM aberrations as initiating core lesions. The effects imposed by TCL1 cooperate with compromised ATM towards a leukemogenic phenotype of impaired DNA damage processing. Dysfunctional ATM appears inefficient in alleviating elevated redox burdens and telomere attrition and in evoking a p53-dependent apoptotic response to genotoxic insults. As non-genotoxic strategies, synergistic combinations of p53 reactivators and deacetylase inhibitors reinstate such cell death execution.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-29T12:14:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002745","title":"Next-Generation Sequencing of AV Nodal Reentry Tachycardia patients","description":"Atrioventricular nodal reentry tachycardia (AVNRT) is the most common form of regular paroxysmal supraventricular tachycardia. This arrhythmia affects women twice as frequently as men, and is often diagnosed in patients below 40 years of age. Familial clustering, early onset of symptoms, and lack of structural anomaly indicate involvement of genetic factors in AVNRT pathophysiology. We hypothesized that AVNRT patients have a high prevalence of variants in genes that are highly expressed in the atrioventricular conduction axis of the heart and potentially involved in arrhythmic diseases. Next-generation sequencing of 67 genes was applied to the DNA profile of 298 AVNRT patients and 10 AVNRT family members using HaloPlex Target Enrichment System.In total, we identified 229 variants in 60 genes; 215 missenses, four frame shifts, four codon deletions, three missense and splice sites, two stop-gain variants, and one start-lost variant. Sixty-five of these were not present in the Exome Aggregation Consortium (ExAC) database. Furthermore, we report two AVNRT families with co-segregating variants. Seventy-five of 284 AVNRT patients (26.4%) and three family members to different AVNRT probands had one or more variants in genes affecting the sodium handling. Fifty-four out of 284 AVNRT patients (19.0%) had variants in genes affecting the calcium handling of the heart. We furthermore find a large proportion of variants in the HCN1-4 genes. We did not detect a significant enrichment of rare variants in the tested genes.This could be an indication that AVNRT might be an electrical arrhythmic disease with abnormal sodium and calcium handling.","abstract":"Atrioventricular nodal reentry tachycardia (AVNRT) is the most common form of regular paroxysmal supraventricular tachycardia. This arrhythmia affects women twice as frequently as men, and is often diagnosed in patients below 40 years of age. Familial clustering, early onset of symptoms, and lack of structural anomaly indicate involvement of genetic factors in AVNRT pathophysiology. We hypothesized that AVNRT patients have a high prevalence of variants in genes that are highly expressed in the atrioventricular conduction axis of the heart and potentially involved in arrhythmic diseases. Next-generation sequencing of 67 genes was applied to the DNA profile of 298 AVNRT patients and 10 AVNRT family members using HaloPlex Target Enrichment System.In total, we identified 229 variants in 60 genes; 215 missenses, four frame shifts, four codon deletions, three missense and splice sites, two stop-gain variants, and one start-lost variant. Sixty-five of these were not present in the Exome Aggregation Consortium (ExAC) database. Furthermore, we report two AVNRT families with co-segregating variants. Seventy-five of 284 AVNRT patients (26.4%) and three family members to different AVNRT probands had one or more variants in genes affecting the sodium handling. Fifty-four out of 284 AVNRT patients (19.0%) had variants in genes affecting the calcium handling of the heart. We furthermore find a large proportion of variants in the HCN1-4 genes. We did not detect a significant enrichment of rare variants in the tested genes.This could be an indication that AVNRT might be an electrical arrhythmic disease with abnormal sodium and calcium handling.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-11-30T11:58:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002746","title":"BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology)","description":"The BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology) study is an ongoing longitudinal, population-based prospective birth cohort including 4,089 children born between 1994 and 1996 in Stockholm, Sweden. The cohort was initially designed to study risk factors for asthma, allergic diseases and lung function in childhood, and to study factors of importance for prognosis at already established disease.Questionnaires on respiratory symptoms and medication were answered at age of 1, 2, 4, 8 and 16 years. Response rates ranged from 96-82% at each occasion with very minor selection bias over the years. Exposure to air pollutants and other environmental factors has been mapped since birth.At the 8 and 16 year follow-up, spirometry and FeNO measurements were performed and at the latter, impulse oscillometry was measured. Blood samples (including plasma) from around 2,500 children were taken at 4, 8 and 16 years and have been analyzed for different IgE-ab and biomarkers. Genome-wide genetic, global methylation and transcriptomic data exist on a subset of the children.","abstract":"The BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology) study is an ongoing longitudinal, population-based prospective birth cohort including 4,089 children born between 1994 and 1996 in Stockholm, Sweden. The cohort was initially designed to study risk factors for asthma, allergic diseases and lung function in childhood, and to study factors of importance for prognosis at already established disease.Questionnaires on respiratory symptoms and medication were answered at age of 1, 2, 4, 8 and 16 years. Response rates ranged from 96-82% at each occasion with very minor selection bias over the years. Exposure to air pollutants and other environmental factors has been mapped since birth.At the 8 and 16 year follow-up, spirometry and FeNO measurements were performed and at the latter, impulse oscillometry was measured. Blood samples (including plasma) from around 2,500 children were taken at 4, 8 and 16 years and have been analyzed for different IgE-ab and biomarkers. Genome-wide genetic, global methylation and transcriptomic data exist on a subset of the children.","study_type":"Other","pubmed_ids":[29496485],"external_links":null,"is_released":true,"released_date":"2017-11-30T17:47:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002747","title":"Somatic_mutation_and_clonal_evolution_in_premalignant_lung_disease___WGS","description":"Cancer is a genetic disease caused by an accumulations of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from the lung tissue of individuals with a variety of lung diseases (COPD, UIP, IPF, Emphysema, pulmonary hypertension). This will allow us to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. Smoking is a large risk factor for developing many of these lung diseases so we are particularly keen to determining whether there is evidence of a smoking signature in these patients.","abstract":"Cancer is a genetic disease caused by an accumulations of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from the lung tissue of individuals with a variety of lung diseases (COPD, UIP, IPF, Emphysema, pulmonary hypertension). This will allow us to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. Smoking is a large risk factor for developing many of these lung diseases so we are particularly keen to determining whether there is evidence of a smoking signature in these patients.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-01T13:24:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002748","title":"My study test - edited","description":null,"abstract":"This is my abstract","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002749","title":"Chromatin_accessability_in_cytokine_induced_immune_cell_states","description":"We isolated T cells and monocotyes from healthy platelet donors and cultured them in resting and stimulated conditions with addition of a range of cytokines. We performed K27Ac ChM sequencing to assess the chromatin activity in different cytokines treated  cells. These cellular profiles were used to map risk variants to the cytokine-induced cell states relevant for autoimmune diseases.","abstract":"Genome wide association studies of autoimmune disease have identified many risk loci implicated in T cell and macrophage activation, differentiation and function. However, most identified risk variants are outside protein coding genes and additionally their activity may only be expressed in specific cell subsets and under limited conditions. Given that the inflammation and and autoimmune tissue distruction is driven by the local production of cytokines, we investigated cytokine induced changes in T cell and macrophage responses by using a combination of immunological and genomics approaches. We assessed the chromatin, transcriptional and proteomic signatures specific for each of the cytokine polarising conditions. These cellular profiles were used to map risk variants to the cytokine-induced cell states relevant for autoimmune diseases.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-04T10:51:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002750","title":"Mitochondrial DNA mutations contribute to autism and also to the characteristics of mitochondrial disorders present in patients with autism spectrum disorders","description":"Intellectual disability (ID) is common among autism spectrum disorder (ASD) patients. Also, evidence from many fields of medicine has documented multiple non-CNS physiological abnormalities associated with ASD, suggesting that, in some individuals, ASD arises from systemic, rather than organ-specific abnormalities. Oxidative phosphorylation and mitochondrial dysfunction are frequently reported in ASD and ID and can be due to mitochondrial DNA mutations. Therefore, the objective of the study was to analyze the mitochondrial DNA of ID subjects with ASD (N=98) and without ASD (N=95) to identify putative pathogenic variants that could be associated with ID or ASD.\nThe genome of reference used in this is study is NC_012920.1 (rCRS) (Homo sapiens mitochondrion).","abstract":"Intellectual disability (ID) is common among autism spectrum disorder (ASD) patients. Also, evidence from many fields of medicine has documented multiple non-CNS physiological abnormalities associated with ASD, suggesting that, in some individuals, ASD arises from systemic, rather than organ-specific abnormalities. Oxidative phosphorylation and mitochondrial dysfunction are frequently reported in ASD and ID and can be due to mitochondrial DNA mutations. Therefore, the objective of the study was to analyze the mitochondrial DNA of ID subjects with ASD (N=98) and without ASD (N=95) to identify putative pathogenic variants that could be associated with ID or ASD.\nThe genome of reference used in this is study is NC_012920.1 (rCRS) (Homo sapiens mitochondrion).","study_type":"Other","pubmed_ids":[29340697],"external_links":null,"is_released":true,"released_date":"2017-12-04T11:49:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002751","title":"Antisense long non-coding RNAs are deregulated in skin tissue of patients with systemic sclerosis","description":"Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and multiple organs of which the pathogenesis is poorly understood. Here we studied differentially expressed coding and non-coding genes in relation to SSc pathogenesis with a specific focus on antisense non-coding RNAs. Skin biopsy-derived RNAs from fourteen early SSc patients and six healthy individuals were sequenced with ion-torrent and analysed using DEseq2. Overall, 4901 genes with a fold change &gt;1.5 and a false discovery rate &lt; 5% were detected in patients versus controls. Upregulated genes clustered in immunological, cell adhesion and keratin-related processes. Interestingly, 676 deregulated non-coding genes were detected, 257 of which were classified as antisense genes. Sense genes expressed opposite of these antisense genes were also deregulated in 42% of the observed sense-antisense gene pairs. The majority of the antisense genes had a similar effect sizes in an independent North American dataset with three genes (CTBP1-AS2, OTUD6B-AS1 and AGAP2-AS1) exceeding the study-wide Bonferroni-corrected ρ-value (PBonf&lt;0.0023, Pcombined = 1.1x10-9, 1.4x10-8, 1.7x10-6, respectively). In this study, we highlight that together with coding genes, (antisense) long non-coding RNAs are deregulated in skin tissue of SSc patients suggesting a novel class of genes involved in pathogenesis of SSc.","abstract":"Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and multiple organs of which the pathogenesis is poorly understood. Here we studied differentially expressed coding and non-coding genes in relation to SSc pathogenesis with a specific focus on antisense non-coding RNAs. Skin biopsy-derived RNAs from fourteen early SSc patients and six healthy individuals were sequenced with ion-torrent and analysed using DEseq2. Overall, 4901 genes with a fold change &gt;1.5 and a false discovery rate &lt; 5% were detected in patients versus controls. Upregulated genes clustered in immunological, cell adhesion and keratin-related processes. Interestingly, 676 deregulated non-coding genes were detected, 257 of which were classified as antisense genes. Sense genes expressed opposite of these antisense genes were also deregulated in 42% of the observed sense-antisense gene pairs. The majority of the antisense genes had a similar effect sizes in an independent North American dataset with three genes (CTBP1-AS2, OTUD6B-AS1 and AGAP2-AS1) exceeding the study-wide Bonferroni-corrected ρ-value (PBonf&lt;0.0023, Pcombined = 1.1x10-9, 1.4x10-8, 1.7x10-6, respectively). In this study, we highlight that together with coding genes, (antisense) long non-coding RNAs are deregulated in skin tissue of SSc patients suggesting a novel class of genes involved in pathogenesis of SSc.","study_type":"Other","pubmed_ids":[29179949],"external_links":null,"is_released":true,"released_date":"2017-12-04T11:50:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002752","title":"Study of the study that I am studying","description":"Trying to figure out if the study, studies, study, jashgdasjhgda, LALALA. SHGDAJHSGDAJHGBcmxscbamsdjkhdiuashfcam.CBM. ,N`C><SCH.sh\\KSJGDBM xcz`zdjhf;oAHD;kadhfkaakdgfhgfhjaDGFjhdgfzjhGFDJdhfb `MNBC`M<~SNV;agsd..ASDH.kasgf,jaHGSDJshagrejfjAHSFV,gfdjlHGDFJHgdfjhsGFJshdgf","abstract":"Trying to figure out if the study, studies, study, jashgdasjhgda, LALALA. SHGDAJHSGDAJHGBcmxscbamsdjkhdiuashfcam.CBM. ,N`C&gt;&lt;SCH.sh\\KSJGDBM xcz`zdjhf;oAHD;kadhfkaakdgfhgfhjaDGFjhdgfzjhGFDJdhfb `MNBC`M&lt;~SNV;agsd..ASDH.kasgf,jaHGSDJshagrejfjAHSFV,gfdjlHGDFJHgdfjhsGFJshdgf","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002753","title":"Defective T-cell expansion in RASGRP1 deficiency","description":"Inherited CTPS1- CD27- and CD70-deficiencies in humans have revealed key factors of T-lymphocyte expansion, that is a prerequisite for an efficient immunity to Epstein-Barr virus (EBV) infection. RASGRP1 is a T-lymphocyte specific nucleotide exchange factor known to activate the MAP kinases pathway. A deleterious homozygous mutation in RASGRP1 leading to the loss RASGRP1 expression was identified in two siblings who both developed a persistent EBV infection leading to Hodgkin lymphoma. RASGRP1-deficient T cells exhibited defective MAPK activation and impaired proliferation that was restored by expression of wild-type RASGRP1. Similar defects were observed in T cells from healthy individuals when RASGRP1 was downregulated. RASGRP1-deficient T cells also exhibited decreased CD27-dependent proliferation toward CD70-expressing EBV-transformed B cells, a crucial pathway required for expansion of antigen-specific T cells in anti-EBV immunity. Furthermore, RASGRP1-deficient T cells failed to upregulate CTPS1, an important enzyme required for DNA synthesis. These results show that RASGRP1 deficiency leads to susceptibility to EBV infection, and demonstrate the key role of RASGRP1 at the crossroad of pathways required for the expansion of activated T lymphocytes.","abstract":"Inherited CTPS1- CD27- and CD70-deficiencies in humans have revealed key factors of T-lymphocyte expansion, that is a prerequisite for an efficient immunity to Epstein-Barr virus (EBV) infection. RASGRP1 is a T-lymphocyte specific nucleotide exchange factor known to activate the MAP kinases pathway. A deleterious homozygous mutation in RASGRP1 leading to the loss RASGRP1 expression was identified in two siblings who both developed a persistent EBV infection leading to Hodgkin lymphoma. RASGRP1-deficient T cells exhibited defective MAPK activation and impaired proliferation that was restored by expression of wild-type RASGRP1. Similar defects were observed in T cells from healthy individuals when RASGRP1 was downregulated. RASGRP1-deficient T cells also exhibited decreased CD27-dependent proliferation toward CD70-expressing EBV-transformed B cells, a crucial pathway required for expansion of antigen-specific T cells in anti-EBV immunity. Furthermore, RASGRP1-deficient T cells failed to upregulate CTPS1, an important enzyme required for DNA synthesis. These results show that RASGRP1 deficiency leads to susceptibility to EBV infection, and demonstrate the key role of RASGRP1 at the crossroad of pathways required for the expansion of activated T lymphocytes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-04T15:45:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002754","title":"IBD_Whole_Genome_Sequencing","description":"Whole genome sequences at 15X depth of patients with Inflammatory Bowel Disease.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Whole genome sequences at 15X depth of patients with Inflammatory Bowel Disease","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-07T13:14:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002755","title":"The European Bank for Induced Pluripotent stem cells (EBiSC) is designed to address the increasing demand by iPSC researchers for quality-controlled, disease-relevant research grade iPSC lines, data and cell services.In this study Whole Genome Sequencing was performed on a selection of lines from the project.","description":"Induced pluripotent stem (iPS) cells have the potential to significantly advance drug development and health research, yet collections of stem cells are scattered across the world, their quality cannot always be guaranteed, and accessing them is often difficult. The goal of EBiSC is to establish a European iPS cell bank that will be the ‘go-to’ resource for the characterisation, storage and distribution of high quality iPS cells. Ultimately, EBiSC will become an independent organisation, distributing high quality iPS cells on a not-for-profit basis to scientists worldwide.","abstract":"Induced pluripotent stem (iPS) cells have the potential to significantly advance drug development and health research, yet collections of stem cells are scattered across the world, their quality cannot always be guaranteed, and accessing them is often difficult. The goal of EBiSC is to establish a European iPS cell bank that will be the ‘go-to’ resource for the characterisation, storage and distribution of high quality iPS cells. Ultimately, EBiSC will become an independent organisation, distributing high quality iPS cells on a not-for-profit basis to scientists worldwide.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-14T12:13:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002756","title":"GWAS in a dengue Thai cohort","description":"Around 700,000 SNPs were genotyped in 290 controls, 252 dengue fever patients and 159 dengue shock syndrome patients from Thailand.","abstract":"Around 700,000 SNPs were genotyped in 290 controls, 252 dengue fever patients and 159 dengue shock syndrome patients from Thailand.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-14T13:46:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002757","title":"Aberrant ERBB4-SRC Signaling as a Hallmark of Group 4 Medulloblastoma Revealed by Integrative Phosphoproteomic Profiling","description":"The four main medulloblastoma subgroups are characterized by distinct biology, clinicopathological features and clinical outcomes. While the WNT and SHH subgroups are characterized by clearly defined aberrant signaling of developmental pathways, the underlying biology of Group 3 and 4 remains poorly understood. Here, we delineate distinct post-translational regulation orchestrating active oncogenic signaling networks in Groups 3 and 4. Specifically, aberrant ERBB4-SRC signaling constitutes a novel hallmark feature of Group 4, with great promise as a novel oncogenic mechanism and potential vulnerability for therapeutic intervention in the most common subgroup. Altogether, this novel integrative proteogenomic landscape demonstrates the added value of proteomics and phosphoproteomics analysis to discover and exploit unexpected oncogenic mechanisms in medulloblastoma and beyond.","abstract":"The four main medulloblastoma subgroups are characterized by distinct biology, clinicopathological features and clinical outcomes. While the WNT and SHH subgroups are characterized by clearly defined aberrant signaling of developmental pathways, the underlying biology of Group 3 and 4 remains poorly understood. Here, we delineate distinct post-translational regulation orchestrating active oncogenic signaling networks in Groups 3 and 4. Specifically, aberrant ERBB4-SRC signaling constitutes a novel hallmark feature of Group 4, with great promise as a novel oncogenic mechanism and potential vulnerability for therapeutic intervention in the most common subgroup. Altogether, this novel integrative proteogenomic landscape demonstrates the added value of proteomics and phosphoproteomics analysis to discover and exploit unexpected oncogenic mechanisms in medulloblastoma and beyond.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-14T14:45:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002758","title":"Colorectal adenomas and carcinomas NKI-AvL TGO series Gut2009","description":"Colorectal cancer (CRC) develops from normal epithelium, through a benign precursor lesion called adenoma, by accumulation of genetic alterations affecting oncogenes and tumour suppressor genes. These CRC-related genomic alterations often result in specific RNA-expression patterns. RNA isolated from fresh frozen specimen of 32 adenomas and 29 CRCs was obtained from the previously published study (Carvalho et al. 2009) and RNA-sequencing was performed with the aim to examine RNA expression changes in colorectal adenoma-to-carcinoma progression.","abstract":"Colorectal cancer (CRC) develops from normal epithelium, through a benign precursor lesion called adenoma, by accumulation of genetic alterations affecting oncogenes and tumour suppressor genes. These CRC-related genomic alterations often result in specific RNA-expression patterns. RNA isolated from fresh frozen specimen of 32 adenomas and 29 CRCs was obtained from the previously published study (Carvalho et al. 2009) and RNA-sequencing was performed with the aim to examine RNA expression changes in colorectal adenoma-to-carcinoma progression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-14T15:46:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002759","title":"NRG1 Fusions in KRAS Wild-type Pancreatic Cancer (H021)","description":"We used whole-genome and transcriptome sequencing to identify clinically actionable gene fusions in young adults with KRAS wild-type (KRASwt) pancreatic ductal adenocarcinoma (PDAC). These alterations included recurrent NRG1 rearrangements predicted to drive PDAC development through aberrant ERBB receptor-mediated signaling, and pharmacologic ERBB inhibition resulted in clinical improvement and remission of liver metastases in two patients with NRG1-rearranged tumors that had proved resistant to standard treatment. Our findings demonstrate that systematic screening of KRASwt tumors for oncogenic fusion genes will substantially improve the therapeutic prospects for a sizeable fraction of PDAC patients.","abstract":"We used whole-genome and transcriptome sequencing to identify clinically actionable gene fusions in young adults with KRAS wild-type (KRASwt) pancreatic ductal adenocarcinoma (PDAC). These alterations included recurrent NRG1 rearrangements predicted to drive PDAC development through aberrant ERBB receptor-mediated signaling, and pharmacologic ERBB inhibition resulted in clinical improvement and remission of liver metastases in two patients with NRG1-rearranged tumors that had proved resistant to standard treatment. Our findings demonstrate that systematic screening of KRASwt tumors for oncogenic fusion genes will substantially improve the therapeutic prospects for a sizeable fraction of PDAC patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-15T09:22:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002760","title":"Germline alterations of acute myeloid leukemia","description":"Germline variants may increase the risk of cancer. A systematic analysis was conducted of a consecutive series of primary and secondary adult acute myeloid leukemia (AML) patients. Exome sequencing was performed on leukemic blasts (somatic) and a skin biopsy (germline) followed by analysis on 35 acute myeloid leukemia or cancer predisposition candidate genes. Exome data were available from 68/80 (85%) patients, and full clinical history was available from all patients. The analysis revealed 34 rare single-nucleotide variants or short indels in 16 genes to be functionally adverse in silico.","abstract":"Germline variants may increase the risk of cancer. A systematic analysis was conducted of a consecutive series of primary and secondary adult acute myeloid leukemia (AML) patients. Exome sequencing was performed on leukemic blasts (somatic) and a skin biopsy (germline) followed by analysis on 35 acute myeloid leukemia or cancer predisposition candidate genes. Exome data were available from 68/80 (85%) patients, and full clinical history was available from all patients. The analysis revealed 34 rare single-nucleotide variants or short indels in 16 genes to be functionally adverse in silico.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-15T12:41:18+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002761","title":"Comprehensive genetic analysis of uveal melanoma heterogeneity during metastatic progression","description":"Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Despite improvement of diagnosis and treatment of the primary tumor, there is no effective treatment of metastatic disease and approximately half of patients will die within one year or less following metastases detection. Tumor heterogeneity has been proposed as a key factor of drug resistance. However, it has been scarcely studied in UM. The present project aims searching for specific drivers of the metastatic progression, describing the genomic and transcriptomic landscape of metastatic UM, exploring tumor heterogeneity and investigating its role in drug resistance. Thus whole exome sequencing and transcriptomics have been performed on constitutional, primary tumor and metastatic samples from 28 UM patients.","abstract":"Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Despite improvement of diagnosis and treatment of the primary tumor, there is no effective treatment of metastatic disease and approximately half of patients will die within one year or less following metastases detection. Tumor heterogeneity has been proposed as a key factor of drug resistance. However, it has been scarcely studied in UM. The present project aims searching for specific drivers of the metastatic progression, describing the genomic and transcriptomic landscape of metastatic UM, exploring tumor heterogeneity and investigating its role in drug resistance. Thus whole exome sequencing and transcriptomics have been performed on constitutional, primary tumor and metastatic samples from 28 UM patients.","study_type":"Other","pubmed_ids":[29760383],"external_links":null,"is_released":true,"released_date":"2017-12-15T14:04:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002762","title":"HSC_population_dynamics_KSP_samples","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Spontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-15T15:34:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002763","title":"Exome array analysis of adverse reactions to fluoropyrimidine-based therapy for gastrointestinal cancer","description":"Fluoropyrimidines, including 5-fluororacil (5FU) and its pro-drug Capecitabine, are the common treatment for colorectal, breast, neck and head cancers – either as monotherapy or in combination therapy. Adverse reactions (ADRs) to the treatment are common and often result in treatment discontinuation or dose reduction. Factors contributing to ADRs, including genetic variation, are poorly characterized. We performed exome array analysis to identify genetic variants that contribute to adverse reactions.Our final dataset consisted of 504 European ancestry individuals undergoing fluoropyrimidine-based therapy for gastrointestinal cancer. A subset of 254 of these were treated with Capecitabine. All individuals were genotyped on the Illumina HumanExome Array.","abstract":"Fluoropyrimidines, including 5-fluororacil (5FU) and its pro-drug Capecitabine, are the common treatment for colorectal, breast, neck and head cancers – either as monotherapy or in combination therapy. Adverse reactions (ADRs) to the treatment are common and often result in treatment discontinuation or dose reduction. Factors contributing to ADRs, including genetic variation, are poorly characterized. We performed exome array analysis to identify genetic variants that contribute to adverse reactions.Our final dataset consisted of 504 European ancestry individuals undergoing fluoropyrimidine-based therapy for gastrointestinal cancer. A subset of 254 of these were treated with Capecitabine. All individuals were genotyped on the Illumina HumanExome Array.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-15T15:03:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002764","title":"Detection and localization of surgically resectable cancers with a multi-analyte blood test","description":"Earlier detection is key to reducing cancer deaths. Here we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1,005 patients with clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast.  CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69% to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals.  The specificity of CancerSEEK was &gt; 99%: only 7 of 812 healthy controls scored positive.  In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.","abstract":"Earlier detection is key to reducing cancer deaths. Here we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1,005 patients with clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast.  CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69% to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals.  The specificity of CancerSEEK was &gt; 99%: only 7 of 812 healthy controls scored positive.  In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.","study_type":"Other","pubmed_ids":[29348365],"external_links":null,"is_released":true,"released_date":"2017-12-16T16:36:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002765","title":"Germline HAVCR2 mutations altering TIM-3 characterize subcutaneous panniculitis-like T-cell lymphomas with hemophagocytic lymphohistiocytic syndrome","description":"Sub-cutaneous panniculitis-like T-cell lymphomas (SPTCL), a non-Hodgkin lymphoma, can be associated with hemophagocytic lymphohistiocytosis (HLH), a life-threatening immune activation which adversely impacts survival1,2. T-cell-immunoglobulin mucin-3 (TIM-3) is a modulator of immune responses expressed on subgroups of T- and innate immune cells. We identify in ~60% of SPTCL cases germline, loss-of-function, missense variants in highly conserved residues of TIM-3, c.245A&gt;G(p.Y82C) and c.291A&gt;G(p.I97M), each with specific geographic distribution. Y82C-TIM-3 occurs on a potential founder chromosome in patients with East Asian and Polynesian ancestry, while I97M-TIM-3 occurs in Caucasians. Both variants induce protein misfolding and abrogate TIM-3’s plasma-membrane expression leading to persistent immune activation, increased production of inflammatory cytokines, including TNF-α and IL-1β, promoting HLH and SPTCL. Our findings highlight HLH/SPTCL as a new genetic entity and showcase TIM-3 mutations as the first causative genetic defect in SPTCL. While TIM-3-mutant HLH/SPTCL benefit from immunomodulation, therapeutic repression of the TIM-3 checkpoint may have adverse consequences.","abstract":"Sub-cutaneous panniculitis-like T-cell lymphomas (SPTCL), a non-Hodgkin lymphoma, can be associated with hemophagocytic lymphohistiocytosis (HLH), a life-threatening immune activation which adversely impacts survival1,2. T-cell-immunoglobulin mucin-3 (TIM-3) is a modulator of immune responses expressed on subgroups of T- and innate immune cells. We identify in ~60% of SPTCL cases germline, loss-of-function, missense variants in highly conserved residues of TIM-3, c.245A&gt;G(p.Y82C) and c.291A&gt;G(p.I97M), each with specific geographic distribution. Y82C-TIM-3 occurs on a potential founder chromosome in patients with East Asian and Polynesian ancestry, while I97M-TIM-3 occurs in Caucasians. Both variants induce protein misfolding and abrogate TIM-3’s plasma-membrane expression leading to persistent immune activation, increased production of inflammatory cytokines, including TNF-α and IL-1β, promoting HLH and SPTCL. Our findings highlight HLH/SPTCL as a new genetic entity and showcase TIM-3 mutations as the first causative genetic defect in SPTCL. While TIM-3-mutant HLH/SPTCL benefit from immunomodulation, therapeutic repression of the TIM-3 checkpoint may have adverse consequences.","study_type":"Other","pubmed_ids":[30374066],"external_links":null,"is_released":true,"released_date":"2017-12-18T04:55:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002766","title":"Co-infection of fungi and bacteria in brain tissue of Alzheimer’s patients.","description":"Metagenomics analysis reveals co-infection of fungi and bacteria isolated from different regions of brain tissue from elderly persons and patients with Alzheimer's disease.","abstract":"Metagenomics analysis reveals co-infection of fungi and bacteria isolated from different regions of brain tissue from elderly persons and patients with Alzheimer's disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-18T11:02:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002767","title":"The genomic and radiomic complexity of multifocal prostate cancer","description":"Multiparametric magnetic resonance imaging (mpMRI) and molecular prognostic tests are emerging to guide screening and prostate cancer (PCa) diagnosis, however their efficacy and cross validation requires further assessment in the context of intraprostatic heterogeneity and patient prognosis. To evaluate the molecular features that make prostate tumors visible to mpMRI, we established an mpMRI-blind multicore collection and performed low pass whole genome, exome, transcriptome and methylation profiling of 14 lesions and 23 representative cores from 6 PCa patients. Our results show that diagnosis based on mpMRI does not capture the genomic complexity of tumors, and reveal that commercial prognostic signature results based on single-biopsy assessments are insufficient to define risk of progression. Altogether, our study supports the use of a multi-biopsy assessment in both mpMRI visible and non-visible areas in order to provide a truly personalised diagnosis","abstract":"Multiparametric magnetic resonance imaging (mpMRI) and molecular prognostic tests are emerging to guide screening and prostate cancer (PCa) diagnosis, however their efficacy and cross validation requires further assessment in the context of intraprostatic heterogeneity and patient prognosis. To evaluate the molecular features that make prostate tumors visible to mpMRI, we established an mpMRI-blind multicore collection and performed low pass whole genome, exome, transcriptome and methylation profiling of 14 lesions and 23 representative cores from 6 PCa patients. Our results show that diagnosis based on mpMRI does not capture the genomic complexity of tumors, and reveal that commercial prognostic signature results based on single-biopsy assessments are insufficient to define risk of progression. Altogether, our study supports the use of a multi-biopsy assessment in both mpMRI visible and non-visible areas in order to provide a truly personalised diagnosis","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-18T11:43:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002768","title":"Genome_Diversity_in_Africa_Project","description":"Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene–disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region.\nThe African Genome Variation Project (AGVP) is an international collaboration that aims to produce a comprehensive catalogue of human genetic variation in SSA. This resource has extended our understanding of population history, patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies.\nThe Genome Diversity in Africa Project (GDAP) will extend and expand the African Genome Variation (AGV) project. Using a sequencing-based approach, GDA project aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out low coverage (4x) whole genome sequencing of up to 2000 individuals across Africa (100 individuals from each ethnolinguistic group), and complement these data with 2.5M Illumina genotyping. We have already completed sequencing of 700 individuals across SSA, we are now adding an additional 500 samples from up to 5 ethno-linguistic groups within Africa, including populations from Burkina Faso, Cameroon, Morocco, Ghana and Seychelles.\nOur scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics.","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out low coverage (4x) whole genome sequencing of up to 2000 individuals across Africa (100 individuals from each ethnolinguistic group), and complement these data with 2.5M Illumina genotyping. We have already completed sequencing of 700 individuals across SSA, we are now adding an additional 500 samples from up to 5 ethno-linguistic groups within Africa, including populations from Burkina Faso, Cameroon, Morocco, Ghana and Seychelles.\nOur scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002769","title":"Insular Celtic population structure and genomic footprints of migration","description":"Previous studies of the genetic landscape of Ireland have suggested homogeneity, with population substructure undetectable using single-marker methods. Here we have harnessed the haplotype-based method fineSTRUCTURE in an Irish genome-wide SNP dataset, identifying 23 discrete genetic clusters which segregate with geographical provenance. Cluster diversity is pronounced in the west of Ireland but reduced in the east where older structure has been eroded by historical migrations. Accordingly, when populations from the neighbouring island of Britain are included, a west-east cline of Celtic-British ancestry is revealed along with a particularly striking correlation between haplotypes and geography across both islands. A strong relationship is revealed between subsets of Northern Irish and Scottish populations, where discordant genetic and geographic affinities reflect major migrations in recent centuries. Additionally, Irish genetic proximity of all Scottish samples likely reflects older strata of communication across the narrowest inter-island crossing.  Using GLOBETROTTER we detected Irish admixture signals from Britain and Europe and estimated dates for events consistent with the historical migrations of the Norse-Vikings, the Anglo-Normans and the British Plantations. The influence of the former is greater than previously estimated from Y chromosome haplotypes. In all, we paint a new picture of the genetic landscape of Ireland, revealing structure which should be considered in the design of studies examining rare genetic variation and its association with traits.","abstract":"Previous studies of the genetic landscape of Ireland have suggested homogeneity, with population substructure undetectable using single-marker methods. Here we have harnessed the haplotype-based method fineSTRUCTURE in an Irish genome-wide SNP dataset, identifying 23 discrete genetic clusters which segregate with geographical provenance. Cluster diversity is pronounced in the west of Ireland but reduced in the east where older structure has been eroded by historical migrations. Accordingly, when populations from the neighbouring island of Britain are included, a west-east cline of Celtic-British ancestry is revealed along with a particularly striking correlation between haplotypes and geography across both islands. A strong relationship is revealed between subsets of Northern Irish and Scottish populations, where discordant genetic and geographic affinities reflect major migrations in recent centuries. Additionally, Irish genetic proximity of all Scottish samples likely reflects older strata of communication across the narrowest inter-island crossing.  Using GLOBETROTTER we detected Irish admixture signals from Britain and Europe and estimated dates for events consistent with the historical migrations of the Norse-Vikings, the Anglo-Normans and the British Plantations. The influence of the former is greater than previously estimated from Y chromosome haplotypes. In all, we paint a new picture of the genetic landscape of Ireland, revealing structure which should be considered in the design of studies examining rare genetic variation and its association with traits.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-18T12:23:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002770","title":"DSRCT RNA genomic sequencing","description":"Purpose: To further understand the molecular pathogenesis of desmoplastic small round cell tumor (DSRCT), a rare but often fatal malignancy occurring primarily in young males, we used next-generation RNA sequencing to investigate the gene expression profiles intrinsic to this disease.Experimental Design: RNA from DSRCT tumor samples were obtained from the Cooperative Human Tissue Network biorepository. RNA sequencing was completed using the Illumina HiSeq 2000 system. Presence of the EWSR1-WT1 fusion was verified using both RNA-sequencing and PCR. Validation studies, including WT1 ChIP-seq, RNA sequencing, and EWS-WT1 knockdown experiments, were performed on an established DSRCT cell line, JN-DSRCT-1. Protein expression of clinically relevant genes determined by RNA sequencing was confirmed using immunohistochemistry. A panel of immune signature genes was also evaluated to identify possible immune therapeutic targets.  Results: We analyzed the RNA from 14 tumor samples, of which two were confirmed negative for the diagnostic EWSR1-WT1 translocation. Principal component analysis of the sequencing data indicated that fusion-negative and fusion-positive tumors are transcriptionally distinct entities.  Overlapping the significant ChIP-seq peaks with genes found to be highly expressed in the RNA sequencing data revealed that IGF2 and FGFR4 were both highly expressed, and targets of the EWS-WT1 fusion gene. This finding has potential clinical relevance for targeted therapeutic intervention. In addition, we identified the immune checkpoints CD200 and CD276 as potentially targetable genes whose expression is independent of the EWS-WT1 fusion gene in vitro.Conclusions: Despite the transcriptional complexity of this disease, we were able to identify IGF2, FGFR4, CD200, and CD276 as potential therapeutic targets for patients suffering from DSRCT.","abstract":"Purpose: To further understand the molecular pathogenesis of desmoplastic small round cell tumor (DSRCT), a rare but often fatal malignancy occurring primarily in young males, we used next-generation RNA sequencing to investigate the gene expression profiles intrinsic to this disease.Experimental Design: RNA from DSRCT tumor samples were obtained from the Cooperative Human Tissue Network biorepository. RNA sequencing was completed using the Illumina HiSeq 2000 system. Presence of the EWSR1-WT1 fusion was verified using both RNA-sequencing and PCR. Validation studies, including WT1 ChIP-seq, RNA sequencing, and EWS-WT1 knockdown experiments, were performed on an established DSRCT cell line, JN-DSRCT-1. Protein expression of clinically relevant genes determined by RNA sequencing was confirmed using immunohistochemistry. A panel of immune signature genes was also evaluated to identify possible immune therapeutic targets.  Results: We analyzed the RNA from 14 tumor samples, of which two were confirmed negative for the diagnostic EWSR1-WT1 translocation. Principal component analysis of the sequencing data indicated that fusion-negative and fusion-positive tumors are transcriptionally distinct entities.  Overlapping the significant ChIP-seq peaks with genes found to be highly expressed in the RNA sequencing data revealed that IGF2 and FGFR4 were both highly expressed, and targets of the EWS-WT1 fusion gene. This finding has potential clinical relevance for targeted therapeutic intervention. In addition, we identified the immune checkpoints CD200 and CD276 as potentially targetable genes whose expression is independent of the EWS-WT1 fusion gene in vitro.Conclusions: Despite the transcriptional complexity of this disease, we were able to identify IGF2, FGFR4, CD200, and CD276 as potential therapeutic targets for patients suffering from DSRCT.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-18T22:05:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002771","title":"Mutational spectrum of highly differentiated, fusion-negative rhabdomyosarcoma (set 2).","description":"Pediatric PAX-FOXO1 fusion-negative rhabdomyosarcoma represents a diverse spectrum of tumors. In this study, the mutational spectrum of 22 fusion-negative rhabdomyosarcomas with high, rhabdomyoma-like levels of differentiation was evaluated using OncoPanel v.2 (OPv2), an Agilent SureSelect custom designed bait set consisting of the coding regions of 504 cancer-relevant genes. Corresponding normal tissue was not available. Discarded normal human skeletal muscle, obtained from 7 donors without tumor history, were also included in the sequencing run.","abstract":"Pediatric PAX-FOXO1 fusion-negative rhabdomyosarcoma represents a diverse spectrum of tumors. In this study, the mutational spectrum of 22 fusion-negative rhabdomyosarcomas with high, rhabdomyoma-like levels of differentiation was evaluated using OncoPanel v.2 (OPv2), an Agilent SureSelect custom designed bait set consisting of the coding regions of 504 cancer-relevant genes. Corresponding normal tissue was not available. Discarded normal human skeletal muscle, obtained from 7 donors without tumor history, were also included in the sequencing run.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-19T10:35:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002772","title":"An integrated molecular study of 20 hepatoblastoma pairs using whole genome sequencing and RNA sequencing","description":"Hepatoblastoma is an uncommon malignant liver cancer occurring in infants and children. The mutant background of hepatoblastoma has not been fully demonstrated. The aim of this study is to genomically depict the mutational landscape of hepatoblastoma through an integrative analysis of whole genome sequencing and RNA sequencing of 20 hepatoblastomas from Chinese individuals.","abstract":"Hepatoblastoma is an uncommon malignant liver cancer occurring in infants and children. The mutant background of hepatoblastoma has not been fully demonstrated. The aim of this study is to genomically depict the mutational landscape of hepatoblastoma through an integrative analysis of whole genome sequencing and RNA sequencing of 20 hepatoblastomas from Chinese individuals.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-20T02:14:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002773","title":"Mutational profiling of LUAD in young never-smokers","description":"NSCLC has been recognized as a highly heterogeneous disease with phenotypic and genotypic diversity in each subgroup. In this study, we conducted whole genome sequencing (WGS) to characterize the genomic alterations of 36 never-smoker Chinese patients with lung adenocarcinomas (LUADs). Our study provides a detailed mutational portrait of LUADs occurring in young never-smokers and gives insights into the molecular pathogenesis of this NSCLC subgroup","abstract":"NSCLC has been recognized as a highly heterogeneous disease with phenotypic and genotypic diversity in each subgroup. In this study, we conducted whole genome sequencing (WGS) to characterize the genomic alterations of 36 never-smoker Chinese patients with lung adenocarcinomas (LUADs). Our study provides a detailed mutational portrait of LUADs occurring in young never-smokers and gives insights into the molecular pathogenesis of this NSCLC subgroup","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-20T10:40:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002774","title":"High-throughput drug screen of medulloblastoma PDOX lines","description":"to come","abstract":"to come","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002775","title":"RNA-seq as a global measure of the similarity between human pluripotent stem cell and fetal liver derived B cell hierarchies","description":"Evidence suggests childhood acute lymphoblastic leukemia (cALL) arises in early human development. Existing models of pre-leukemic initiation by ETV6-RUNX1 have not faithfully recapitulated human disease, highlighting the need for a developmentally relevant human model system. We generated a human pluripotent stem cell (hPSC) model genome engineered to express ETV6-RUNX1 from the endogenous ETV6 promoter. In vitro B cell differentiation of hPSCs recapitulated human fetal B lymphopoiesis at the global transcriptional level. Furthermore, hPSC-derived IL7R+ early lymphoid progenitors show a switch from myeloid to lymphoid lineage priming during culture, recapitulating a transition that we also observed in first trimester fetal liver. ETV6-RUNX1 impairs B lineage commitment from hPSC IL7R+ lymphoid progenitors and ETV6-RUNX1+ proB cells aberrantly co-express B and myeloid genes and retain myeloid potential. We propose that the distinct lineage dynamics of fetal IL7R+ early lymphoid progenitors provide a developmental susceptibility to pre-leukemic initiation by ETV6-RUNX1.","abstract":"Evidence suggests childhood acute lymphoblastic leukemia (cALL) arises in early human development. Existing models of pre-leukemic initiation by ETV6-RUNX1 have not faithfully recapitulated human disease, highlighting the need for a developmentally relevant human model system. We generated a human pluripotent stem cell (hPSC) model genome engineered to express ETV6-RUNX1 from the endogenous ETV6 promoter. In vitro B cell differentiation of hPSCs recapitulated human fetal B lymphopoiesis at the global transcriptional level. Furthermore, hPSC-derived IL7R+ early lymphoid progenitors show a switch from myeloid to lymphoid lineage priming during culture, recapitulating a transition that we also observed in first trimester fetal liver. ETV6-RUNX1 impairs B lineage commitment from hPSC IL7R+ lymphoid progenitors and ETV6-RUNX1+ proB cells aberrantly co-express B and myeloid genes and retain myeloid potential. We propose that the distinct lineage dynamics of fetal IL7R+ early lymphoid progenitors provide a developmental susceptibility to pre-leukemic initiation by ETV6-RUNX1.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002776","title":"Hoorn Diabetes Care System (DCS) Cohort","description":"The Hoorn DCS dataset contains phenotype and genotype (GWAS) data from ~3400 subjects with type 2 diabetes. Longitudinal phenotype data were collected annually. Both individual and metadata are available. Individual level data can only be accessed via the AMP-T2D knowledge portal. http://www.type2diabetesgenetics.org/\nRecently we also generated small RNA-sequencing data on 470 subjects.","abstract":"The Hoorn DCS dataset contains phenotype and genotype (GWAS) data from ~3400 subjects with type 2 diabetes. Longitudinal phenotype data were collected annually. Both individual and metadata are available. Individual level data can only be accessed via the AMP-T2D knowledge portal. http://www.type2diabetesgenetics.org/\nRecently we also generated small RNA-sequencing data on 470 subjects.","study_type":"Other","pubmed_ids":[28588112],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002777","title":"Phylogenetic analysis of treatment-naive metastases using whole exome and genome sequencing data","description":"Metastases are responsible for the majority of cancer related deaths and are often difficult to treat successfully. Even for metastases that occur subsequent to treatment, we do not know whether such relapsing metastases were originally heterogeneous or if the observed heterogeneity is a consequence of therapy. Given that treatment can influence evolutionary dynamics by selecting resistant clones, imposing bottlenecks on cancer cell populations, and even inducing novel somatic mutations, characterizing the prior standing variation among metastases remains an important goal to predict initial therapeutic response. To quantify the heterogeneity at clinical presentation of advanced disease, we surveyed the literature for patients in which at least two treatment-naïve metastases underwent genome/exome-wide sequencing. Across all cancer types surveyed, only 18 subjects were found to fulfill this requirement. Including previously unpublished data from two subjects, we analyzed data of 74 untreated metastases and inferred cancer phylogenies. Putative driver gene mutations were acquired at a 2-fold higher rate on the trunk of all metastases than on branches. Mutations in driver genes along the trunk were strongly enriched for predicted functional consequences. Using a stochastic mathematical model, we find that driver gene heterogeneity among metastases mostly occurs in slowly growing cancers for highly advantageous driver gene mutations. Seeding efficiency only weakly affects the heterogeneity among metastases. These results explain why functional driver gene heterogeneity is uncommon in advanced disease prior to treatment, thus providing optimism for future therapies that depend on mutations across metastases.","abstract":"Metastases are responsible for the majority of cancer related deaths and are often difficult to treat successfully. Even for metastases that occur subsequent to treatment, we do not know whether such relapsing metastases were originally heterogeneous or if the observed heterogeneity is a consequence of therapy. Given that treatment can influence evolutionary dynamics by selecting resistant clones, imposing bottlenecks on cancer cell populations, and even inducing novel somatic mutations, characterizing the prior standing variation among metastases remains an important goal to predict initial therapeutic response. To quantify the heterogeneity at clinical presentation of advanced disease, we surveyed the literature for patients in which at least two treatment-naïve metastases underwent genome/exome-wide sequencing. Across all cancer types surveyed, only 18 subjects were found to fulfill this requirement. Including previously unpublished data from two subjects, we analyzed data of 74 untreated metastases and inferred cancer phylogenies. Putative driver gene mutations were acquired at a 2-fold higher rate on the trunk of all metastases than on branches. Mutations in driver genes along the trunk were strongly enriched for predicted functional consequences. Using a stochastic mathematical model, we find that driver gene heterogeneity among metastases mostly occurs in slowly growing cancers for highly advantageous driver gene mutations. Seeding efficiency only weakly affects the heterogeneity among metastases. These results explain why functional driver gene heterogeneity is uncommon in advanced disease prior to treatment, thus providing optimism for future therapies that depend on mutations across metastases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-21T17:00:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002778","title":"Evolutionary analysis of pancreatic cancer and coexistent precursor lesions using whole exome sequencing data","description":"Most adult carcinomas develop from noninvasive precursor lesions, a progression that is supported by genetic analysis. Further, the evolution of these lesions contextualizes the dynamics of advanced stage disease. We analyzed the somatic variants of co-existing pancreatic cancers and precursor lesions sampled from distinct regions of the same pancreas. After inferring evolutionary relationships, we found that the ancestral cell had initiated and clonally expanded to form one or more lesions, and that subsequent driver gene mutations eventually led to a pancreatic cancer. We also found that this multi-step progression generally spans many years. Our data suggest that independent, high-grade pancreatic lesions observed in a histologic cross section often represent a single neoplasm that can spread and colonize the ductal system, accumulating spatial and genetic divergence over time.","abstract":"Most adult carcinomas develop from noninvasive precursor lesions, a progression that is supported by genetic analysis. Further, the evolution of these lesions contextualizes the dynamics of advanced stage disease. We analyzed the somatic variants of co-existing pancreatic cancers and precursor lesions sampled from distinct regions of the same pancreas. After inferring evolutionary relationships, we found that the ancestral cell had initiated and clonally expanded to form one or more lesions, and that subsequent driver gene mutations eventually led to a pancreatic cancer. We also found that this multi-step progression generally spans many years. Our data suggest that independent, high-grade pancreatic lesions observed in a histologic cross section often represent a single neoplasm that can spread and colonize the ductal system, accumulating spatial and genetic divergence over time.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-21T17:11:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002779","title":"Chromekrexis: a distinct and detrimental pattern of complex genomic rearrangements","description":"Cancer presents with a diversity of chromosomal rearrangement phenotypes that are the combined result of gradual evolutionary selection and single-step massive rearrangement events called, chromoanagenesis (Holland and Cleveland Nat Med. 2012 Nov;18(11):1630-8. The term Chromotripsis is used for single-step shattering events that give rise to intermittent single gains and losses as well as high level amplifications (Nature Reviews Cancer 12, 663-670 (October 2012). In 2 % (8/420) of metastatic colorectal cancers (mCRCs)(ref to haan &amp; Mekenkamp) we observed clusters of multiple (N=3-30) high-level amplifications with sharp boundaries, intermitted by a constant non-amplified copy number level, in an otherwise common copy number background. We observed this phenomenon in various malignancies, with up to 100 (Daoud?) high level clustered amplifications, that are particularly common in higher grade tumors (Pieter&amp;Daphne&amp;other pathologists help wording, GBMs, dedifferentiated liposarcomas, pediatric MYCN, tumors with lower overall survival)) and introduced the term chromekrexis (“chrom” for chromosome and “ekrexis” Greek for eruption). We observe that amplifications within a Chromekrexis region are not necessarily all of the same amplitude, and physically attached to each other in a complex web of rearrangements indicative of double minute formation (Nick’s section). We provide evidence for Chromekrexis as a late onset event, of aggressive tumor behavior that significantly correlates with a worse overall survival. Given the distinct pattern of complex genomic rearrangements, and the absence of the characteristic intermittent single copy number gains and losses of chromothripsis, chromekrexis should be recognized as an independent chromoanagenesis mechnism that can confer detrimental growth advantages across tumor types.","abstract":"Cancer presents with a diversity of chromosomal rearrangement phenotypes that are the combined result of gradual evolutionary selection and single-step massive rearrangement events called, chromoanagenesis (Holland and Cleveland Nat Med. 2012 Nov;18(11):1630-8. The term Chromotripsis is used for single-step shattering events that give rise to intermittent single gains and losses as well as high level amplifications (Nature Reviews Cancer 12, 663-670 (October 2012). In 2 % (8/420) of metastatic colorectal cancers (mCRCs)(ref to haan &amp; Mekenkamp) we observed clusters of multiple (N=3-30) high-level amplifications with sharp boundaries, intermitted by a constant non-amplified copy number level, in an otherwise common copy number background. We observed this phenomenon in various malignancies, with up to 100 (Daoud?) high level clustered amplifications, that are particularly common in higher grade tumors (Pieter&amp;Daphne&amp;other pathologists help wording, GBMs, dedifferentiated liposarcomas, pediatric MYCN, tumors with lower overall survival)) and introduced the term chromekrexis (“chrom” for chromosome and “ekrexis” Greek for eruption). We observe that amplifications within a Chromekrexis region are not necessarily all of the same amplitude, and physically attached to each other in a complex web of rearrangements indicative of double minute formation (Nick’s section). We provide evidence for Chromekrexis as a late onset event, of aggressive tumor behavior that significantly correlates with a worse overall survival. Given the distinct pattern of complex genomic rearrangements, and the absence of the characteristic intermittent single copy number gains and losses of chromothripsis, chromekrexis should be recognized as an independent chromoanagenesis mechnism that can confer detrimental growth advantages across tumor types.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002780","title":"Investigating the genetic cause of diabetes and hyperinsulinism","description":"This study includes samples sequenced for the investigation of neonatal diabetes, MODY, hyperinsulinism, and related diseases.","abstract":"This study includes samples sequenced for the investigation of neonatal diabetes, MODY, hyperinsulinism, and related diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002781","title":"Whole genome bisulphite sequencing (WGBS) of induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (DAn) generated by cell reprogramming of somatic skin cells from PD patients","description":"In this study we expanded the knowledge of alterations in DNA methylation associated to PD described previously (Illumina array; Fernandez-Santiago et al., 2015. EMBO Mol Med), by performing WGBS in three scenerios (1 control, 1 genetic PD and 1 sporadic PD), in order to have a complete epigenetic picture of all the genome.","abstract":"In this study we expanded the knowledge of alterations in DNA methylation associated to PD described previously (Illumina array; Fernandez-Santiago et al., 2015. EMBO Mol Med), by performing WGBS in three scenerios (1 control, 1 genetic PD and 1 sporadic PD), in order to have a complete epigenetic picture of all the genome.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002782","title":"Kibbutzim Family study","description":"The Kibbutzim Family Study (KFS) was established in 1992 to investigate the environmental and genetic determinants of cardiometabolic risk factors and their change over time. The participants belong to large families living in close-knit communities, called “Kibbutzim”, in Northern Israel. The Kibbutz has been a communal settlement, which has created a relatively homogeneous environment for its members. Kibbutz members are mostly of Ashkenazi Jewish ancestry, with the remaining members belonging to other Jewish subgroups. Participants were recruited in two phases from six Kibbutzim. In the first recruitment phase of the study (1992–1993) 500 individuals from 80 extended families (range 2 to 43) were examined. During the second phase (1999–2000), all participants from the first phase were invited for repeat examinations (80% response rate) and additional new participants were recruited, giving a total of 922 individuals from 150 extended families (range 2 to 55). Families were invited to participate if they consisted of at least four individuals who (i) lived in the Kibbutz, (ii) spanned at least two generations, and (iii) were at least 15 years old. Families were retained if at least two family members consented to participate in the study. Overall, 1033 participants were recruited; 111 were examined only in the first phase, 533 only in the second phase, and 389 were included in both. 901 individuals were successfully genotyped using Illumina HumanCoreExome BeadChip.","abstract":"The Kibbutzim Family Study (KFS) was established in 1992 to investigate the environmental and genetic determinants of cardiometabolic risk factors and their change over time. The participants belong to large families living in close-knit communities, called “Kibbutzim”, in Northern Israel. The Kibbutz has been a communal settlement, which has created a relatively homogeneous environment for its members. Kibbutz members are mostly of Ashkenazi Jewish ancestry, with the remaining members belonging to other Jewish subgroups. Participants were recruited in two phases from six Kibbutzim. In the first recruitment phase of the study (1992–1993) 500 individuals from 80 extended families (range 2 to 43) were examined. During the second phase (1999–2000), all participants from the first phase were invited for repeat examinations (80% response rate) and additional new participants were recruited, giving a total of 922 individuals from 150 extended families (range 2 to 55). Families were invited to participate if they consisted of at least four individuals who (i) lived in the Kibbutz, (ii) spanned at least two generations, and (iii) were at least 15 years old. Families were retained if at least two family members consented to participate in the study. Overall, 1033 participants were recruited; 111 were examined only in the first phase, 533 only in the second phase, and 389 were included in both. 901 individuals were successfully genotyped using Illumina HumanCoreExome BeadChip.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-12-28T09:23:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002783","title":"Whole-exome sequencing reveals the origin and evolution of Hepato-Cholangiocarcinoma","description":"Hepatocellular-cholangiocarcinoma (H-ChC) is a rare subtype of liver cancer with clinicopathological features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). To date, molecular mechanisms underlying the co-existence of HCC and iCCA components in a single tumor remain elusive. Here we show that H-ChC samples contain substantial private mutations from WES analyses, ranging from 33.1% to 86.4%, indicative of substantive intratumor heterogeneity (ITH). However, on the other hand, numerous ubiquitous mutations shared by HCC and iCCA suggest the monoclonal origin of H-ChC. Mutated genes identify herein e.g. VCAN, ACVR2A and FCGBP are speculated to contribute to distinct differentiation of HCC and iCCA within H-ChC. Moreover, immunohistochemistry demonstrate that EpCAM is highly expressed in 80% of H-ChC implying the stemness of such liver cancer. In summary, our data highlight the monoclonal origin and stemness of H-ChC, as well as substantial intratumoral heterogeneity.","abstract":"Hepatocellular-cholangiocarcinoma (H-ChC) is a rare subtype of liver cancer with clinicopathological features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). To date, molecular mechanisms underlying the co-existence of HCC and iCCA components in a single tumor remain elusive. Here we show that H-ChC samples contain substantial private mutations from WES analyses, ranging from 33.1% to 86.4%, indicative of substantive intratumor heterogeneity (ITH). However, on the other hand, numerous ubiquitous mutations shared by HCC and iCCA suggest the monoclonal origin of H-ChC. Mutated genes identify herein e.g. VCAN, ACVR2A and FCGBP are speculated to contribute to distinct differentiation of HCC and iCCA within H-ChC. Moreover, immunohistochemistry demonstrate that EpCAM is highly expressed in 80% of H-ChC implying the stemness of such liver cancer. In summary, our data highlight the monoclonal origin and stemness of H-ChC, as well as substantial intratumoral heterogeneity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-01T13:32:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002784","title":"Patient-derived organoids model treatment response of metastatic gastrointestinal cancers (targeted and whole-genome sequencing)","description":"Patient-derived organoids (PDOs) have recently emerged as robust pre-clinical models, however, their potential to predict patient clinical outcomes remain unclear. We report a living biobank of PDOs from metastatic, heavily-pretreated colorectal and gastroesophageal cancer patients recruited in phase I/II clinical trials.  Phenotypic and genotypic profiling of PDOs showed a high-degree of similarity to the original patient tumor.  Molecular profiling of tumor organoids was matched to drug screening results, suggesting PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. We compared ex vivo organoid responses to anticancer agents, and PDO-based orthotopic mouse tumor xenograft models to the response of the patient in clinical trials.  Our data suggest that PDOs can recapitulate patient responses in the clinic, and have the potential to be implemented in personalized medicine programs.","abstract":"Patient-derived organoids (PDOs) have recently emerged as robust pre-clinical models, however, their potential to predict patient clinical outcomes remain unclear. We report a living biobank of PDOs from metastatic, heavily-pretreated colorectal and gastroesophageal cancer patients recruited in phase I/II clinical trials.  Phenotypic and genotypic profiling of PDOs showed a high-degree of similarity to the original patient tumor.  Molecular profiling of tumor organoids was matched to drug screening results, suggesting PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. We compared ex vivo organoid responses to anticancer agents, and PDO-based orthotopic mouse tumor xenograft models to the response of the patient in clinical trials.  Our data suggest that PDOs can recapitulate patient responses in the clinic, and have the potential to be implemented in personalized medicine programs.","study_type":"Other","pubmed_ids":[29472484],"external_links":null,"is_released":true,"released_date":"2018-01-02T10:11:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002785","title":"RNA_sequencing_of_CHD1L_knock_out_iPSC","description":"We have generated CRISPR homozygous and heterozygotes frame shift knockouts of CHD1L from KOS iPSC lines.Three independent homozygotes clones, two heterozygotes and one wild type have been expanded and differentiated into macrophages for further experiments. Total RNA sequencing as well as Western blots have been carried out in iPSC clones to confirm the lack of gene product in knockout clones in comparison with wild type clones.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"We have generated CRISPR homozygous and heterozygotes frame shift knockouts of CHD1L from KOS iPSC lines.Three independent homozygotes clones, two heterozygotes and one wild type have been expanded and differentiated into macrophages for further experiments. Total RNA sequencing as well as Western blots have been carried out in iPSC clones to confirm the lack of gene product in knockout clones in comparison with wild type clones.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002786","title":"An Empirical Approach Leveraging Tumorgrafts to Dissect the Tumor Microenvironment in Renal Cell Carcinoma Identifies Missing Link to Prognostic Inflammatory Factors","description":"We undertook an empirical approach to dissect the tumor microenvironment by developing a bulk tumor dissection algorithm, DisHet, and leveraging RNA-Seq data of tumorgrafts (patient-derived tumors implanted in mice), in which only the tumor cell component expands. We found that approximately 65% of previously defined immune signature genes are not abundantly expressed in the Renal Cell Carcinoma (RCC) microenvironment, and we identified more than two times as many novel immune/stromal transcripts. By using refined immune/stroma-specific genes and genomics, electronic medical record data and imaging data  of 1084 RCC patients, we discovered a highly-inflamed pan-RCC subtype enriched for Treg cells, NK cells, Th1 cells, neutrophils, macrophages, B cells, and CD8+ T cells. This inflamed subtype (IS) is enriched for aggressive RCCs, including BAP1-deficient clear-cell and type 2 papillary tumors. Interestingly, IS is correlated with systemic manifestations of inflammation in patients such as thrombocytosis and anemia, whose pathogenesis were poorly defined and have been predictors of poor prognosis in RCC. Indeed, we discovered that IS is a strong predictor of poor survival. Lastly, our analyses show that tumor cells may drive stromal immune response. Overall, these data provide a missing link between the tumor cells, the tumor microenvironment, and systemic factors.","abstract":"We undertook an empirical approach to dissect the tumor microenvironment by developing a bulk tumor dissection algorithm, DisHet, and leveraging RNA-Seq data of tumorgrafts (patient-derived tumors implanted in mice), in which only the tumor cell component expands. We found that approximately 65% of previously defined immune signature genes are not abundantly expressed in the Renal Cell Carcinoma (RCC) microenvironment, and we identified more than two times as many novel immune/stromal transcripts. By using refined immune/stroma-specific genes and genomics, electronic medical record data and imaging data  of 1084 RCC patients, we discovered a highly-inflamed pan-RCC subtype enriched for Treg cells, NK cells, Th1 cells, neutrophils, macrophages, B cells, and CD8+ T cells. This inflamed subtype (IS) is enriched for aggressive RCCs, including BAP1-deficient clear-cell and type 2 papillary tumors. Interestingly, IS is correlated with systemic manifestations of inflammation in patients such as thrombocytosis and anemia, whose pathogenesis were poorly defined and have been predictors of poor prognosis in RCC. Indeed, we discovered that IS is a strong predictor of poor survival. Lastly, our analyses show that tumor cells may drive stromal immune response. Overall, these data provide a missing link between the tumor cells, the tumor microenvironment, and systemic factors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-04T16:40:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002787","title":"Whole_Genome_Sequencing_of_INTERVAL","description":"15x Whole Genome Sequencing of 15,000 individuals from the INTERVAL study cohort, phase III.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"15x Whole Genome Sequencing of 15,000 individuals from the INTERVAL study cohort, phase III.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-05T13:40:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002788","title":"Genomic analysis Nasopharyngeal cancer through whole exome sequencing and whole genomic sequencing.","description":"Nasopharyngeal carcinoma (NPC) is a squamous-cell carcinoma and has remarkable ethnic and geographic distribution, with a high prevalence in southern China, southeast Asia, northern Africa and Alaska. Although there are previous studies implicated NF-κB pathway play an important role in NPC. Newer research also found several important cellular processes and pathways in NPC, including chromatin modification, ERBB-PI3K signaling and autophagy machinery. Put these studies together, although, NPC is still poorly understood at the genetic level. Here we determined the mutational landscape of 553 cases with NPC using whole-genomic and whole-exome sequencing. These approaches revealed a distinct mutational signature and significantly mutated genes.","abstract":"Nasopharyngeal carcinoma (NPC) is a squamous-cell carcinoma and has remarkable ethnic and geographic distribution, with a high prevalence in southern China, southeast Asia, northern Africa and Alaska. Although there are previous studies implicated NF-κB pathway play an important role in NPC. Newer research also found several important cellular processes and pathways in NPC, including chromatin modification, ERBB-PI3K signaling and autophagy machinery. Put these studies together, although, NPC is still poorly understood at the genetic level. Here we determined the mutational landscape of 553 cases with NPC using whole-genomic and whole-exome sequencing. These approaches revealed a distinct mutational signature and significantly mutated genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-08T03:35:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002789","title":"CD49f single-cell methylomes","description":"Single-cell DNA methylation has emerged as a powerful tool to study molecular heterogeneity within cellular populations. We report the development of a bisulfite based whole genome protocol suitable for use on single index sorted primary mammalian cells. Application of this protocol to human hematopoietic stem cells provided quantitative DNA methylation measurements of up to 5.7 million CpGs in a single cell. Analysis of cis CpG methylation states in single cells revealed a loss of concordance beyond 2kb, which supported the development of a new analytical framework (PDclust) for single-cell DNA methylation datasets that considers heterogeneity of methylation states at single CpG resolution. PDclust identified epigenetically distinct subpopulations within highly purified and functionally defined human stem cell populations. In silico merging of the methylation states from the single cells allowed us to ascribe function to these epigenetically distinct subpopulations on the basis of their epigenetic states.","abstract":"Single-cell DNA methylation has emerged as a powerful tool to study molecular heterogeneity within cellular populations. We report the development of a bisulfite based whole genome protocol suitable for use on single index sorted primary mammalian cells. Application of this protocol to human hematopoietic stem cells provided quantitative DNA methylation measurements of up to 5.7 million CpGs in a single cell. Analysis of cis CpG methylation states in single cells revealed a loss of concordance beyond 2kb, which supported the development of a new analytical framework (PDclust) for single-cell DNA methylation datasets that considers heterogeneity of methylation states at single CpG resolution. PDclust identified epigenetically distinct subpopulations within highly purified and functionally defined human stem cell populations. In silico merging of the methylation states from the single cells allowed us to ascribe function to these epigenetically distinct subpopulations on the basis of their epigenetic states.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-09T21:26:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002790","title":"Preferential infiltration of distinct Vγ9δ2 T cells into Glioblastoma multiforme","description":"Glioblastoma multiforme (GBM),  the most fatal CNS cancer, is highly infiltrative as a result of phenotypic alteration of cancer cells mainly driven by a mutual interaction among cancer cells, tumor-associated macrophages (TAMs) and other stromal cells. This work aims at characterizing GBM-infiltrating γδ T cells that may regulate the GBM tumor microenvironment and cancer cell gene expression. V(D)J repertoires of tumor-infiltrating and blood circulating γδ T cells from 4 patients were analyzed by NGS-based TCR sequencing. RNA gene expression profiling and immunostaining of cancer tissues were performed as well.","abstract":"Glioblastoma multiforme (GBM),  the most fatal CNS cancer, is highly infiltrative as a result of phenotypic alteration of cancer cells mainly driven by a mutual interaction among cancer cells, tumor-associated macrophages (TAMs) and other stromal cells. This work aims at characterizing GBM-infiltrating γδ T cells that may regulate the GBM tumor microenvironment and cancer cell gene expression. V(D)J repertoires of tumor-infiltrating and blood circulating γδ T cells from 4 patients were analyzed by NGS-based TCR sequencing. RNA gene expression profiling and immunostaining of cancer tissues were performed as well.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-10T01:41:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002791","title":"Deep single-cell RNA sequencing data for 11138 T cells from tumour, adjacent normal tissue and peripheral blood of treatment-naive CRC patients. The DATA ACCESS AGREEMENT is provided at https://github.com/zhangyybio/single-T-cell-data-access. Applicants can request access to the data by directly downloading it or by sending an email to cancerpku@pku.edu.cn. The process that is used to approve an application includes verifying the institution, participants and research purposes of the application. In general this process will take about two weeks. In principal, any scientific research program complying with the laws and bioethic regulation policies of China will be approved.","description":"T cells are central players in cancer immunotherapy1, yet some of their fundamental properties such as development and migration within tumours remain elusive. The enormous T cell receptor (TCR) repertoire, required for recognising foreign and self-antigens2,3, could serve as lineage tags to track these T cells in tumours4. Here, we obtained transcriptomes of 11,138 single T cells from 12 colorectal cancer (CRC) patients and developed STARTRAC (Single T-cell Analysis by Rna-seq and Tcr TRACking) indices to quantitatively analyse dynamic relationships among 20 identified T cell subsets with distinct functions and clonalities. While both CD8+ effector and “exhausted” T cells exhibited high clonal expansion, they were independently connected with tumour-resident CD8+ effector memory cells, implicating a TCR-based fate decision. Of the CD4+ T cells, the majority of tumour-infiltrating Tregs showed clonal exclusivity, whereas certain Treg clones were developmentally linked to multiple TH clones. Notably, we identified two IFNG+ TH1-like clusters in tumours, the GZMK+ TEM and CXCL13+ TH1-like clusters, which were associated with distinct IFN-γ-regulating transcription factors, EOMES/RUNX3 and BHLHE40, respectively. Only CXCL13+BHLHE40+ TH1-like cells were preferentially enriched in tumours of microsatellite-instable (MSI) patients, which might explain their favourable response rates to immune-checkpoint blockade. Furthermore, we found IGFLR1 to be highly expressed in both CXCL13+BHLHE40+ TH1-like and CD8+ exhausted T cells and possessed co-stimulatory functions. Our integrated STARTRAC analyses provides a powerful avenue to comprehensively dissect the T cell properties in CRC, which could shed new insights into the dynamic relationships of T cells in other cancers","abstract":"T cells are central players in cancer immunotherapy1, yet some of their fundamental properties such as development and migration within tumours remain elusive. The enormous T cell receptor (TCR) repertoire, required for recognising foreign and self-antigens2,3, could serve as lineage tags to track these T cells in tumours4. Here, we obtained transcriptomes of 11,138 single T cells from 12 colorectal cancer (CRC) patients and developed STARTRAC (Single T-cell Analysis by Rna-seq and Tcr TRACking) indices to quantitatively analyse dynamic relationships among 20 identified T cell subsets with distinct functions and clonalities. While both CD8+ effector and “exhausted” T cells exhibited high clonal expansion, they were independently connected with tumour-resident CD8+ effector memory cells, implicating a TCR-based fate decision. Of the CD4+ T cells, the majority of tumour-infiltrating Tregs showed clonal exclusivity, whereas certain Treg clones were developmentally linked to multiple TH clones. Notably, we identified two IFNG+ TH1-like clusters in tumours, the GZMK+ TEM and CXCL13+ TH1-like clusters, which were associated with distinct IFN-γ-regulating transcription factors, EOMES/RUNX3 and BHLHE40, respectively. Only CXCL13+BHLHE40+ TH1-like cells were preferentially enriched in tumours of microsatellite-instable (MSI) patients, which might explain their favourable response rates to immune-checkpoint blockade. Furthermore, we found IGFLR1 to be highly expressed in both CXCL13+BHLHE40+ TH1-like and CD8+ exhausted T cells and possessed co-stimulatory functions. Our integrated STARTRAC analyses provides a powerful avenue to comprehensively dissect the T cell properties in CRC, which could shed new insights into the dynamic relationships of T cells in other cancers","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-10T03:13:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002792","title":"Breast cancer DNA repair","description":"Tumors of germline BRCA1/2 mutated carriers show homologous recombination (HR) deficiency (HRD), resulting in impaired DNA double strand break (DSB) repair and high sensitivity to Poly-(ADP-Ribose)-Polymerase (PARP) inhibitors. Although this therapy is expected to be effective beyond germline BRCA1/2 mutated carriers, a robust validated test to detect HRD tumors is lacking. In the present study we therefore evaluated a functional HR assay exploiting the formation of RAD51 foci in proliferating cells after ex vivo irradiation of fresh breast cancers (BrC) tissue: the RECAP test.Methods Fresh samples of 170 primary BrC were analyzed using the RECAP test. The molecular explanation for the HRD phenotype was investigated by exploring BRCA deficiencies, mutational signatures, tumor infiltrating lymphocytes (TILs) and microsatellite instability (MSI).Results RECAP was completed successfully in 148 out of 170 samples (87%). 24 tumors showed HRD (16%), while 6 tumors were HR intermediate (HRi) (4%). HRD was explained by BRCA deficiencies (mutations, promoter hypermethylation, deletions) in 16 cases. Several non-BRCA deficient HRD tumors showed BRCAness mutational signatures, suggesting that they are also bona fide HRD cases. HRD tumors showed an increased incidence of high TIL counts (p=0.023) compared to HR proficient (HRP) tumors and MSI was more frequently observed in the HRD group (2/20, 10%) than expected in BrC (1%) (p=0.017).Conclusion The RECAP test is a robust assay detecting both BRCA1/2 deficient and BRCA1/2 proficient HRD tumors, suggesting that this test identifies approximately 50% more patients that may benefit from PARPi treatment than BRCA gene testing only.","abstract":"Tumors of germline BRCA1/2 mutated carriers show homologous recombination (HR) deficiency (HRD), resulting in impaired DNA double strand break (DSB) repair and high sensitivity to Poly-(ADP-Ribose)-Polymerase (PARP) inhibitors. Although this therapy is expected to be effective beyond germline BRCA1/2 mutated carriers, a robust validated test to detect HRD tumors is lacking. In the present study we therefore evaluated a functional HR assay exploiting the formation of RAD51 foci in proliferating cells after ex vivo irradiation of fresh breast cancers (BrC) tissue: the RECAP test.Methods Fresh samples of 170 primary BrC were analyzed using the RECAP test. The molecular explanation for the HRD phenotype was investigated by exploring BRCA deficiencies, mutational signatures, tumor infiltrating lymphocytes (TILs) and microsatellite instability (MSI).Results RECAP was completed successfully in 148 out of 170 samples (87%). 24 tumors showed HRD (16%), while 6 tumors were HR intermediate (HRi) (4%). HRD was explained by BRCA deficiencies (mutations, promoter hypermethylation, deletions) in 16 cases. Several non-BRCA deficient HRD tumors showed BRCAness mutational signatures, suggesting that they are also bona fide HRD cases. HRD tumors showed an increased incidence of high TIL counts (p=0.023) compared to HR proficient (HRP) tumors and MSI was more frequently observed in the HRD group (2/20, 10%) than expected in BrC (1%) (p=0.017).Conclusion The RECAP test is a robust assay detecting both BRCA1/2 deficient and BRCA1/2 proficient HRD tumors, suggesting that this test identifies approximately 50% more patients that may benefit from PARPi treatment than BRCA gene testing only.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-10T10:51:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002793","title":"TRACERx Renal 100","description":"Evolutionary dynamics of clear cell renal cell carcinoma (ccRCC) have not been studied prospectively or across all disease stages. Through the multi-centre prospective cohort study, Renal TRACERx Renal, we analysed 1209 primary tumour regions from 101 patients with ccRCC. We detect up to 30 driver events in a single tumour, and show that subclonal diversification is associated with known clinical parameters. Defining driver event co-occurrence, mutual exclusivity and timing at clone level, we reveal deterministic patterns of clonal evolution and disease progression. We find that ccRCC can be grouped into seven distinct evolutionary subtypes, ranging from tumours characterised by early fixation of multiple mutational and copy number driver events that can disseminate widely and rapidly; to highly branched tumours with &gt;10 subclonal drivers and extensive parallel evolution presenting with oligometastatic disease. We identify either heterogeneity or chromosome instability, or both, as determinants of patient outcome.  Our insights reconcile the variable clinical behaviour of ccRCC and the benefit of surgical intervention in early and late-stage disease; and offer potential biomarker opportunities to maximise the benefit of both surgery and active surveillance.","abstract":"Evolutionary dynamics of clear cell renal cell carcinoma (ccRCC) have not been studied prospectively or across all disease stages. Through the multi-centre prospective cohort study, Renal TRACERx Renal, we analysed 1209 primary tumour regions from 101 patients with ccRCC. We detect up to 30 driver events in a single tumour, and show that subclonal diversification is associated with known clinical parameters. Defining driver event co-occurrence, mutual exclusivity and timing at clone level, we reveal deterministic patterns of clonal evolution and disease progression. We find that ccRCC can be grouped into seven distinct evolutionary subtypes, ranging from tumours characterised by early fixation of multiple mutational and copy number driver events that can disseminate widely and rapidly; to highly branched tumours with &gt;10 subclonal drivers and extensive parallel evolution presenting with oligometastatic disease. We identify either heterogeneity or chromosome instability, or both, as determinants of patient outcome.  Our insights reconcile the variable clinical behaviour of ccRCC and the benefit of surgical intervention in early and late-stage disease; and offer potential biomarker opportunities to maximise the benefit of both surgery and active surveillance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-10T15:38:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002794","title":"The Estonian Biocentre Human Genome Diversity Panel (EGDP)","description":"Previous human genetic studies, based on sampling small numbers of populations, have supported a recent out-of-Africa dispersal model with minor additional input from archaic humans. Here, we present a novel dataset of 377 (two additional genomes are accessible through EGA  through managed access program)  high-coverage human genomes from 125 populations worldwide. The combination of high spatial and genomic coverage enabled us to refine current knowledge of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size. The examined Papuan genomes (hereafter taken as representative of the broader Sahul region) show an excess of haplotype sharing with Africans. This is compatible with traces of an early and otherwise extinct non-African lineage in the Papuan genome, evidence of which was so far only available in the Western Asian fossil record. Our tests of positive and balancing selection highlight a number of new metabolism- and immunity-related loci as candidates for local adaptation.","abstract":"Previous human genetic studies, based on sampling small numbers of populations, have supported a recent out-of-Africa dispersal model with minor additional input from archaic humans. Here, we present a novel dataset of 377 (two additional genomes are accessible through EGA  through managed access program)  high-coverage human genomes from 125 populations worldwide. The combination of high spatial and genomic coverage enabled us to refine current knowledge of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size. The examined Papuan genomes (hereafter taken as representative of the broader Sahul region) show an excess of haplotype sharing with Africans. This is compatible with traces of an early and otherwise extinct non-African lineage in the Papuan genome, evidence of which was so far only available in the Western Asian fossil record. Our tests of positive and balancing selection highlight a number of new metabolism- and immunity-related loci as candidates for local adaptation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002795","title":"Molecular profiling of acinar cell carcinoma of the salivary glands","description":"Samples of acinar cell carcinoma (AciCC) of the salivary glands and paired normal salivary gland tissue were analyzed by whole transcriptome RNA-seq (n=10), whole genome sequencing (n=6), whole genome bisulfite sequencing (n=3) and ChIP-seq (H3K27ac, H3K4me3, H3K27me3, NR4A3, CTCF).","abstract":"Samples of acinar cell carcinoma (AciCC) of the salivary glands and paired normal salivary gland tissue were analyzed by whole transcriptome RNA-seq (n=10), whole genome sequencing (n=6), whole genome bisulfite sequencing (n=3) and ChIP-seq (H3K27ac, H3K4me3, H3K27me3, NR4A3, CTCF).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-11T12:40:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002796","title":"Somatic IL4R Hotspot Mutations in Primary Mediastinal Large B-cell lymphoma lead to constitutive JAK-STAT activation","description":"Primary mediastinal large B cell lymphoma (PMBCL) is a distinct subtype of diffuse large B cell lymphoma thought to arise from thymic medullary B cells. Gene mutations underlying the molecular pathogenesis of the disease are incompletely characterized. Here, we describe novel somatic IL4R mutations in 15 out of 62 primary cases of PMBCL (24.2%) and in all PMBCL-derived cell lines tested. The majority of mutations (11/21; 52%) were hotspot single nucleotide variants in exon 8 leading to an I242N amino acid change in the transmembrane domain. Functional analyses establish this mutation as gain-of-function leading to constitutive activation of the JAK-STAT pathway and upregulation of downstream cytokine expression profiles and B cell specific antigens. Moreover, expression of I242N mutant IL4R in a mouse xenotransplantation model conferred growth advantage in vivo. The pattern of concurrent mutations within the JAK-STAT signaling pathway suggests additive/synergistic effects of these gene mutations contributing to lymphomagenesis. Our data establish IL4R mutations as novel driver alterations and provide a strong preclinical rationale for therapeutic targeting of JAK-STAT signaling in PMBCL.","abstract":"Primary mediastinal large B cell lymphoma (PMBCL) is a distinct subtype of diffuse large B cell lymphoma thought to arise from thymic medullary B cells. Gene mutations underlying the molecular pathogenesis of the disease are incompletely characterized. Here, we describe novel somatic IL4R mutations in 15 out of 62 primary cases of PMBCL (24.2%) and in all PMBCL-derived cell lines tested. The majority of mutations (11/21; 52%) were hotspot single nucleotide variants in exon 8 leading to an I242N amino acid change in the transmembrane domain. Functional analyses establish this mutation as gain-of-function leading to constitutive activation of the JAK-STAT pathway and upregulation of downstream cytokine expression profiles and B cell specific antigens. Moreover, expression of I242N mutant IL4R in a mouse xenotransplantation model conferred growth advantage in vivo. The pattern of concurrent mutations within the JAK-STAT signaling pathway suggests additive/synergistic effects of these gene mutations contributing to lymphomagenesis. Our data establish IL4R mutations as novel driver alterations and provide a strong preclinical rationale for therapeutic targeting of JAK-STAT signaling in PMBCL.","study_type":"Other","pubmed_ids":[29467182],"external_links":null,"is_released":true,"released_date":"2018-01-11T19:13:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002797","title":"DNA hypermethylation and differential gene expression associated with Klinefelter syndrome","description":"The molecular basis for the phenotypic traits and morbidity in Klinefelter syndrome (KS) are not clarified. As DNA methylation affect gene expression and thereby play a role in disease susceptibility, we performed genome-wide DNA methylation profiling of leucocytes from peripheral blood samples from 67 KS patients, 67 male controls and 33 female controls, in addition to genome-wide RNA-sequencing profiling in a subset of 9 KS patients, 9 control males and 13 female controls. Characterization of the methylome as well as the transcriptome of both coding and non-coding genes identified a unique epigenetic and genetic landscape of both autosomal chromosomes as well as the X chromosome in KS. A subset of genes show significant correlation between methylation values and expression values. Gene set enrichment analysis of differentially methylated positions yielded terms associated with well-known comorbidities seen in KS. In addition, differentially expressed genes revealed enrichment for genes involved in the immune system, wnt-signaling pathway and neuron development. Based on our data we point towards many new candidate genes (AKAP17A, AMOT, APOB, DACT1, DDX58, DOCK7, EIF2S3, FIGNL1, G3BP1, HENMT1, HERC5, IFI44, IFI44L, IFIT1, IFIT3, ISG15, KANK1, LGALS1, NSD1, PEX10, PLSCR1, RSAD2, SHROOM2, SLC25A6, SPEG, SPON2, TXLNG), which may be implicated in the phenotype and further point towards non-coding genes (RP13-216E22.4, RP13-36G14.4, G087825, G088512), which may be involved in X chromosome inactivation in KS and in the regulation of escape genes.","abstract":"The molecular basis for the phenotypic traits and morbidity in Klinefelter syndrome (KS) are not clarified. As DNA methylation affect gene expression and thereby play a role in disease susceptibility, we performed genome-wide DNA methylation profiling of leucocytes from peripheral blood samples from 67 KS patients, 67 male controls and 33 female controls, in addition to genome-wide RNA-sequencing profiling in a subset of 9 KS patients, 9 control males and 13 female controls. Characterization of the methylome as well as the transcriptome of both coding and non-coding genes identified a unique epigenetic and genetic landscape of both autosomal chromosomes as well as the X chromosome in KS. A subset of genes show significant correlation between methylation values and expression values. Gene set enrichment analysis of differentially methylated positions yielded terms associated with well-known comorbidities seen in KS. In addition, differentially expressed genes revealed enrichment for genes involved in the immune system, wnt-signaling pathway and neuron development. Based on our data we point towards many new candidate genes (AKAP17A, AMOT, APOB, DACT1, DDX58, DOCK7, EIF2S3, FIGNL1, G3BP1, HENMT1, HERC5, IFI44, IFI44L, IFIT1, IFIT3, ISG15, KANK1, LGALS1, NSD1, PEX10, PLSCR1, RSAD2, SHROOM2, SLC25A6, SPEG, SPON2, TXLNG), which may be implicated in the phenotype and further point towards non-coding genes (RP13-216E22.4, RP13-36G14.4, G087825, G088512), which may be involved in X chromosome inactivation in KS and in the regulation of escape genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-12T15:24:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002798","title":"Hominin-specific NOTCH2 paralogs expand human cortical neurogenesis through regulation of Delta/Notch interactions.","description":"The human cerebral cortex has undergone rapid expansion and increased complexity during recent evolution. Hominid-specific gene duplications represent a major driving force of evolution, but their impact on human brain evolution remains unclear. Using tailored RNA sequencing (RNAseq), we profiled the spatial and temporal expression of Hominid-specific duplicated (HS) genes in the human fetal cortex, leading to the identification of a repertoire of 36 HS genes displaying robust and dynamic patterns during cortical neurogenesis. Among these we focused on NOTCH2NL, previously uncharacterized HS paralogs of NOTCH2. NOTCH2NL promote the clonal expansion of human cortical progenitors by increasing self-renewal, ultimately leading to higher neuronal output. NOTCH2NL function by activating the Notch pathway, through inhibition of Delta/Notch interactions. Our study uncovers a large repertoire of recently evolved genes linking genomic evolution to human brain development, and reveals how hominin-specific NOTCH paralogs may have contributed to the expansion of the human cortex.\n\nThe dataset contains raw sequences (FASTQ files) from the Illumina 2x150bp paired-end RNA sequencing profiles of 11 fetal human brain samples at 7, 9, 12, 15 and 21 gestational weeks.","abstract":"The human cerebral cortex has undergone rapid expansion and increased complexity during recent evolution. Hominid-specific gene duplications represent a major driving force of evolution, but their impact on human brain evolution remains unclear. Using tailored RNA sequencing (RNAseq), we profiled the spatial and temporal expression of Hominid-specific duplicated (HS) genes in the human fetal cortex, leading to the identification of a repertoire of 36 HS genes displaying robust and dynamic patterns during cortical neurogenesis. Among these we focused on NOTCH2NL, previously uncharacterized HS paralogs of NOTCH2. NOTCH2NL promote the clonal expansion of human cortical progenitors by increasing self-renewal, ultimately leading to higher neuronal output. NOTCH2NL function by activating the Notch pathway, through inhibition of Delta/Notch interactions. Our study uncovers a large repertoire of recently evolved genes linking genomic evolution to human brain development, and reveals how hominin-specific NOTCH paralogs may have contributed to the expansion of the human cortex.\n\nThe dataset contains raw sequences (FASTQ files) from the Illumina 2x150bp paired-end RNA sequencing profiles of 11 fetal human brain samples at 7, 9, 12, 15 and 21 gestational weeks.","study_type":"Other","pubmed_ids":[29856955],"external_links":null,"is_released":true,"released_date":"2018-01-15T13:41:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002799","title":"Epigenetic profiling of colorectal cancer initiating cells (CC-ICs) to identify bivalently marked genes (H3K4me3 and H3K27me3 ChIP-seq), and investigation of changes in transcriptome following EZH2 inhibition using RNA-seq.","description":"Epigenetic regulation of transcription plays a crucial role in lineage commitment of embryonic stem cells. Promoters of key lineage-specific differentiation genes are found in a repressed “bivalent state”, having both activating H3K4me3 and repressive H3K27me3 histone marks, making them “poised” for transcription upon loss of H3K27me3 in response to environmental cues. Whether the tumour-initiating, self-renewing, cancer-initiating cells (C-ICs) have similar epigenetic regulatory mechanism that prevent lineage commitment is unknown. In order to investigate bivalently marked and repressed promoters, we used a patient-derived CC-IC enriched model to identify the changes in transcriptome following inhibition of EZH2, the H3K27 methyltransferase. We also performed ChIP-seq for H3K27me3 and H3K4me3 at baseline in order to identify repressed and bivalently marked promoters.","abstract":"Epigenetic regulation of transcription plays a crucial role in lineage commitment of embryonic stem cells. Promoters of key lineage-specific differentiation genes are found in a repressed “bivalent state”, having both activating H3K4me3 and repressive H3K27me3 histone marks, making them “poised” for transcription upon loss of H3K27me3 in response to environmental cues. Whether the tumour-initiating, self-renewing, cancer-initiating cells (C-ICs) have similar epigenetic regulatory mechanism that prevent lineage commitment is unknown. In order to investigate bivalently marked and repressed promoters, we used a patient-derived CC-IC enriched model to identify the changes in transcriptome following inhibition of EZH2, the H3K27 methyltransferase. We also performed ChIP-seq for H3K27me3 and H3K4me3 at baseline in order to identify repressed and bivalently marked promoters.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002800","title":"ICGC27 Testing","description":"EGASub testing for Release 27","abstract":"EGASub testing for Release 27","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002801","title":"Analysis of Complex Genomic Rearrangements of Lung Adenocarcinomas","description":"Lung adenocarcinomas (LADC) are heterogeneous disease with distinct etiology. A majority of tumors are related with tobacco smoking, and some tumors arise from never-smoking or young patients, whose clinical history do not support the environmental carcinogen-induced oncogenes. Here we analyzed complex rearrangements in lung adenocarcinomas including tumors with distinct etiologies.","abstract":"Lung adenocarcinomas (LADC) are heterogeneous disease with distinct etiology. A majority of tumors are related with tobacco smoking, and some tumors arise from never-smoking or young patients, whose clinical history do not support the environmental carcinogen-induced oncogenes. Here we analyzed complex rearrangements in lung adenocarcinomas including tumors with distinct etiologies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-16T05:41:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002802","title":"RNA-seq profiling of NKX6.1 reporter iPSC lines for isolation and analysis of functionally relevant neuronal and pancreas populations","description":"We generated human induced pluripotent stem cell (iPSC) lines with a GFP reporter inserted in the endogenous NKX6.1 locus. Characterisation of the reporter lines demonstrated faithful GFP labelling of NKX6.1 expression during pancreas and motor neuron differentiation. We performed three independent in vitro differentiations towards the pancreatic endocrine lineage. We FACS-purified GFP positive and negative cells from stage 7 cultures, and generated Smart-Seq2 RNA-sequencing libraries for the pre-sorted cells, as well as the two GFP-sorted cell populations. Gene expression profiling by RNA-sequencing reveals that the NKX6.1-positive population closely resembles mature human beta cells and the functional evaluation of purified populations shows that the glucose-responsive beta-like cells are enriched within the NKX6.1-positive population. These reporter lines provide a valuable resource to the scientific community for the derivation of functional relevant pancreas and neuronal cell subtypes.","abstract":"We generated human induced pluripotent stem cell (iPSC) lines with a GFP reporter inserted in the endogenous NKX6.1 locus. Characterisation of the reporter lines demonstrated faithful GFP labelling of NKX6.1 expression during pancreas and motor neuron differentiation. We performed three independent in vitro differentiations towards the pancreatic endocrine lineage. We FACS-purified GFP positive and negative cells from stage 7 cultures, and generated Smart-Seq2 RNA-sequencing libraries for the pre-sorted cells, as well as the two GFP-sorted cell populations. Gene expression profiling by RNA-sequencing reveals that the NKX6.1-positive population closely resembles mature human beta cells and the functional evaluation of purified populations shows that the glucose-responsive beta-like cells are enriched within the NKX6.1-positive population. These reporter lines provide a valuable resource to the scientific community for the derivation of functional relevant pancreas and neuronal cell subtypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-16T10:56:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002803","title":"Sensitive and Frequent Identification of High Avidity Neo-epitope Specific CD8 + T-cells in Immunotherapy-naïve Ovarian Cancer","description":"Immunotherapy directed against private tumor neo-antigens derived from non-synonymous somatic mutations is a promising strategy of personalized cancer immunotherapy. However, feasibility in low mutational load tumor types remains unknown. Comprehensive and deep analysis of circulating and tumor-infiltrating lymphocytes (TILs) for neo-epitope specific CD8 + T cells allowed prompt identification of oligoclonal and polyfunctional such cells from most immunotherapy-naïve patients with advanced epithelial ovarian cancer studied. Neo-epitope recognition was discordant between circulating T cells and TILs, and was more likely to be found among TILs, which displayed higher functionalavidity and unique TCRs with higher predicted affinity than their blood counterparts. Our results imply that identification of neo-epitope specific CD8 + T cells is achievable even in tumors with relatively low number of somatic mutations, and neo-epitope validation in TILs extends opportunities for mutanome-based personalized immunotherapies to such tumors.","abstract":"Immunotherapy directed against private tumor neo-antigens derived from non-synonymous somatic mutations is a promising strategy of personalized cancer immunotherapy. However, feasibility in low mutational load tumor types remains unknown. Comprehensive and deep analysis of circulating and tumor-infiltrating lymphocytes (TILs) for neo-epitope specific CD8 + T cells allowed prompt identification of oligoclonal and polyfunctional such cells from most immunotherapy-naïve patients with advanced epithelial ovarian cancer studied. Neo-epitope recognition was discordant between circulating T cells and TILs, and was more likely to be found among TILs, which displayed higher functionalavidity and unique TCRs with higher predicted affinity than their blood counterparts. Our results imply that identification of neo-epitope specific CD8 + T cells is achievable even in tumors with relatively low number of somatic mutations, and neo-epitope validation in TILs extends opportunities for mutanome-based personalized immunotherapies to such tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-18T09:19:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002804","title":"2018_ETO_WGS","description":"This study includes 12 paired samples of Korean AML-ETO paitients.12 AML-ETO tumor samples are paired with each normal(Saliva or BM derived) sequencing data.The results of this WGS study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.","abstract":"This study includes 12 paired samples of Korean AML-ETO paitients.12 AML-ETO tumor samples are paired with each normal(Saliva or BM derived) sequencing data.The results of this WGS study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-19T04:55:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002805","title":"Predictor_RIO_TNBC","description":"In this study, samples fom a window study of the PARP inhibitor rucaparib in patients with primary triple negative or BRCA1/2 related breast cancer (RIO trial) will be investigated. Samples will undergo whole genome sequence and analysis, including use of HR Predict.","abstract":"In this study, samples fom a window study of the PARP inhibitor rucaparib in patients with primary triple negative or BRCA1/2 related breast cancer (RIO trial) will be investigated. Samples will undergo whole genome sequence and analysis, including use of HR Predict.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-19T12:59:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002806","title":"Predictor_ChemoNEAR_TNBC","description":"In this study a collection of core biopsies from breast cancer patients receiving neoadjuvant chemotherapy as part of the ChemoNEAR trial will be investigated. The study is intended to detect early acquired resistance in women with diagnosed breast carcinoma. Samples will undergo whole genome sequencing and analysis, including use of HR Predict.","abstract":"In this study a collection of core biopsies from breast cancer patients receiving neoadjuvant chemotherapy as part of the ChemoNEAR trial will be investigated. The study is intended to detect early acquired resistance in women with diagnosed breast carcinoma. Samples will undergo whole genome sequencing and analysis, including use of HR Predict.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-19T13:01:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002807","title":"Genomic profiling of matched well differentiated and de-differentiated liposarcoma.","description":"Well-differentiated (WD) and de-differentiated (DD) liposarcoma, subtypes of adipocytic sarcomas, are pathologically and clinically dissimilar, but are poorly distinguishable at the molecular level. These tumors harbor neochromosomes formed from amplifications and rearrangements of chr12q. Nineteen selected patients with matched WD and DD tumors underwent extensive exomic and transcriptomic profiling to distinguish genomic features between the two subtypes. Shared point mutations suggest a common tumor origin and de-differentiated tumors have higher burdens of deletions.","abstract":"Well-differentiated (WD) and de-differentiated (DD) liposarcoma, subtypes of adipocytic sarcomas, are pathologically and clinically dissimilar, but are poorly distinguishable at the molecular level. These tumors harbor neochromosomes formed from amplifications and rearrangements of chr12q. Nineteen selected patients with matched WD and DD tumors underwent extensive exomic and transcriptomic profiling to distinguish genomic features between the two subtypes. Shared point mutations suggest a common tumor origin and de-differentiated tumors have higher burdens of deletions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-19T19:45:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002808","title":"HipSci ChiPseq Normal_and_disease","description":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we perform ChIPseq on iPS lines from a subset of healthy and disease samples.","abstract":"The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we perform ChIPseq on iPS lines from a subset of healthy and disease samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002809","title":"Inherited genetic predisposition to childhood acute lymphoblastic leukemia investigated using a genome wide association study.","description":"This series consists of summary data generated from a genome-wide association study (GWAS) investigating inherited genetic risk to childhood acute lymphoblastic leukemia (ALL). The GWAS comprised 784 cases recruited to  the Medical Research Council UK ALL-2003 and ALL-97/99 trials and 7,385 controls. The data describe SNPtest association statistics from the case-control analysis.","abstract":"This series consists of summary data generated from a genome-wide association study (GWAS) investigating inherited genetic risk to childhood acute lymphoblastic leukemia (ALL). The GWAS comprised 784 cases recruited to  the Medical Research Council UK ALL-2003 and ALL-97/99 trials and 7,385 controls. The data describe SNPtest association statistics from the case-control analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-23T10:55:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002810","title":"Role_of_Cell_Division_during_Mesendoderm_formation___ChIP_seq_analysis","description":"We have demonstrated that pluripotent stem cells divide two times during endoderm differentiation. The first division occur at about 20h after the induction of differentiation.  In order to determine whether this cell division is couple to the epigenetic changes that take place during this differentiation process, we carried out ChIP-seq experiments for two histone marks widely known for their role in specification of active and inactive gene promoter enhancers (H3K27Ac and H3K4me1). These experiments are accompanied by RNA seq analysis.\nTo this end, we conducted the following: H9 cells were synchronized in G2/M and then differentiated into endoderm for 24h, in presence or absence of different agents capable of blocking cells in specific phases of the cell cycle (Hydroxyurea: S-phase; Nocodazole: G2/M phase). Cells were collected at different time points. 12h after differentiation: Majority of the cells should be in S phase. In presence of Hidroxyurea (HU), cells should not live S phase and therefore, by the end of the experiment (24h-HU) those cells should still be in S phase; Nocodazole (Noc) was added after 12h of differentiation with the goal of blocking cells in the first G2/M phase during differentiation. Majority of these cells should be in G2/M by the end of the experiment (24h-Noc). Synchronized cells that differentiated normally in absence of these two drugs (E24h), will pass the first cell division, and be manly in G1/S phases of the cell cycle.","abstract":"We have demonstrated that pluripotent stem cells divide two times during endoderm differentiation. The first division occur at about 20h after the induction of differentiation.  In order to determine whether this cell division is couple to the epigenetic changes that take place during this differentiation process, we carried out ChIP-seq experiments for two histone marks widely known for their role in specification of active and inactive gene promoter enhancers (H3K27Ac and H3K4me1). These experiments are accompanied by RNA seq analysis.\nTo this end, we conducted the following: H9 cells were synchronized in G2/M and then differentiated into endoderm for 24h, in presence or absence of different agents capable of blocking cells in specific phases of the cell cycle (Hydroxyurea: S-phase; Nocodazole: G2/M phase). Cells were collected at different time points. 12h after differentiation: Majority of the cells should be in S phase. In presence of Hidroxyurea (HU), cells should not live S phase and therefore, by the end of the experiment (24h-HU) those cells should still be in S phase; Nocodazole (Noc) was added after 12h of differentiation with the goal of blocking cells in the first G2/M phase during differentiation. Majority of these cells should be in G2/M by the end of the experiment (24h-Noc). Synchronized cells that differentiated normally in absence of these two drugs (E24h), will pass the first cell division, and be manly in G1/S phases of the cell cycle.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002811","title":"Whole-Exome Sequencing of Salivary Gland Mucoepidermoid Carcinoma","description":"Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. To explore the genetic origins of MEC, we performed systematic genomic analyses of these tumors.Experimental DesignWhole-exome sequencing and gene copy number analyses were performed for 18 primary cancers with matched normal tissue. Fluorescence in situ hybridization (FISH) was used to determine the presence or absence of the MECT1-MAML2 translocation in 17 tumors.ResultsTP53 was the most commonly mutated gene in MEC (28%), and mutations were found only in intermediate- and high-grade tumors. Tumors with TP53 mutations had more mutations overall than tumors without TP53 mutations (p=0.006). POU6F2 was the second most frequently mutated gene, found in three low-grade MECs with the same in-frame deletion. Somatic alterations in IRAK1, MAP3K9, ITGAL, ERBB4, OTOGL, KMT2C, and OBSCN were identified in at least two of the 18 tumors sequenced. FISH analysis confirmed the presence of the MECT1-MAML2 translocation in 15 of 17 tumors (88%).ConclusionsThrough these integrated genomic analyses, MECT1-MAML2 translocation and somatic TP53 and POU6F2 mutations appear to be the main drivers of mucoepidermoid carcinoma.","abstract":"Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. To explore the genetic origins of MEC, we performed systematic genomic analyses of these tumors.Experimental DesignWhole-exome sequencing and gene copy number analyses were performed for 18 primary cancers with matched normal tissue. Fluorescence in situ hybridization (FISH) was used to determine the presence or absence of the MECT1-MAML2 translocation in 17 tumors.ResultsTP53 was the most commonly mutated gene in MEC (28%), and mutations were found only in intermediate- and high-grade tumors. Tumors with TP53 mutations had more mutations overall than tumors without TP53 mutations (p=0.006). POU6F2 was the second most frequently mutated gene, found in three low-grade MECs with the same in-frame deletion. Somatic alterations in IRAK1, MAP3K9, ITGAL, ERBB4, OTOGL, KMT2C, and OBSCN were identified in at least two of the 18 tumors sequenced. FISH analysis confirmed the presence of the MECT1-MAML2 translocation in 15 of 17 tumors (88%).ConclusionsThrough these integrated genomic analyses, MECT1-MAML2 translocation and somatic TP53 and POU6F2 mutations appear to be the main drivers of mucoepidermoid carcinoma.","study_type":"Other","pubmed_ids":[5182193],"external_links":null,"is_released":true,"released_date":"2018-01-23T15:41:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002812","title":"Whole-Genome Sequencing of Salivary Gland Adenoid Cystic Carcinoma","description":"Adenoid cystic carcinomas (ACCs) of the salivary glands are challenging to understand, treat, and cure. To better understand the genetic alterations underlying the pathogenesis of these tumors, we performed comprehensive genome analyses of 25 fresh-frozen tumors, including whole genome sequencing, expression and pathway analyses. In addition to the well-described MYB-NFIB fusion which was found in 11 tumors (44%), we observed five different rearrangements involving the NFIB transcription factor gene in seven tumors (28%). Taken together, NFIB translocations occurred in 15 of 25 samples (60%, 95%CI=41–77%). In addition, mRNA expression analysis of 17 tumors revealed overexpression of NFIB in ACC tumors compared with normal tissues (p=0.002). There was no difference in NFIB mRNA expression in tumors with NFIB fusions compared to those without. We also report somatic mutations of genes involved in the axonal guidance and Rho family signaling pathways. Finally, we confirm previously described alterations in genes related to chromatin regulation and Notch signaling. Our findings suggest a separate role for NFIB in ACC oncogenesis and highlight important signaling pathways for future functional characterization and potential therapeutic targeting.","abstract":"Adenoid cystic carcinomas (ACCs) of the salivary glands are challenging to understand, treat, and cure. To better understand the genetic alterations underlying the pathogenesis of these tumors, we performed comprehensive genome analyses of 25 fresh-frozen tumors, including whole genome sequencing, expression and pathway analyses. In addition to the well-described MYB-NFIB fusion which was found in 11 tumors (44%), we observed five different rearrangements involving the NFIB transcription factor gene in seven tumors (28%). Taken together, NFIB translocations occurred in 15 of 25 samples (60%, 95%CI=41–77%). In addition, mRNA expression analysis of 17 tumors revealed overexpression of NFIB in ACC tumors compared with normal tissues (p=0.002). There was no difference in NFIB mRNA expression in tumors with NFIB fusions compared to those without. We also report somatic mutations of genes involved in the axonal guidance and Rho family signaling pathways. Finally, we confirm previously described alterations in genes related to chromatin regulation and Notch signaling. Our findings suggest a separate role for NFIB in ACC oncogenesis and highlight important signaling pathways for future functional characterization and potential therapeutic targeting.","study_type":"Other","pubmed_ids":[4818686],"external_links":null,"is_released":true,"released_date":"2018-01-23T15:43:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002813","title":"Gene_regulation_of_human_CD4__Treg_cells_","description":"Gene regulation of human CD4+ Treg cells \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Recently, we identified that immune disease associated variants are enriched in active promoters (marked by H3K4me3 modification) specific to CD4+ T lymphocytes, especially in regulatory T cells (Tregs). This enrichment suggests that a proportion of associated variants is likely to confer disease risk by modulating gene-expression in CD4-positive subsets of T cells. Here, we aim to further study the effects of disease associated variants - specifically we want to assess if different alleles can lead to imbalanced histone modification levels, differences in chromatin open regions and altered gene expression. We will perform RNA-seq, ATAC-seq and ChIP-seq on Tcells isolated from over 100 healthy blood donors.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002814","title":"Natural variation of circulating RNAs in human serum","description":"Non-coding RNA (ncRNA) molecules have fundamental roles in cells and many are also stable in body fluids as extracellular RNAs. In these studies, we used RNA sequencing (RNA-seq) to investigate the profile of small non-coding RNA (sncRNA) in human serum. We analyzed more than 10 billion Illumina reads from more than 500 serum samples, included in the Norwegian population-based Janus Serum Bank (JSB). Our results suggest that many circulating RNAs in serum can be potential biomarkers and they are associated with different traits including age, sex, smoking, body size etc.","abstract":"Non-coding RNA (ncRNA) molecules have fundamental roles in cells and many are also stable in body fluids as extracellular RNAs. In these studies, we used RNA sequencing (RNA-seq) to investigate the profile of small non-coding RNA (sncRNA) in human serum. We analyzed more than 10 billion Illumina reads from more than 500 serum samples, included in the Norwegian population-based Janus Serum Bank (JSB). Our results suggest that many circulating RNAs in serum can be potential biomarkers and they are associated with different traits including age, sex, smoking, body size etc.","study_type":"Other","pubmed_ids":[29219730],"external_links":null,"is_released":true,"released_date":"2018-01-24T08:42:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002815","title":"Cancer sequencing study - edited","description":null,"abstract":"Genomic libraries (500 bps) will be generated from total \ngenomic DNA derived from CLL cancer samples and subjected to total of eight lanes of 37 bp, paired end sequencing on the llumina GA. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002816","title":"Prostate Cancer and Normal Adjacent Prostate RNA-seq samples, NGS-ProToCol","description":"The dataset \"Prostate Cancer and Normal Adjacent Prostate RNA-seq samples, NGS-ProToCol\" includes 41 Normal Adjacent Prostate and 51 ribo-depleted Prostate Cancer RNA-seq samples.\n----\nDetection of fusion transcripts and their genomic breakpoints from RNA sequencing data\nYouri Hoogstrate, Malgorzata A. Komor, René Böttcher, Job van Riet, Harmen J. G. van de Werken, Stef van Lieshout, Ralf Hoffmann, Evert van den Broek, Anne S. Bolijn, Natasja Dits, Daoud Sie, David van der Meer, Floor Pepers, Chris H. Bangma, Geert J. L. H. van Leenders, Marcel Smid, Pim French, John W.M. Martens, Wilbert van Workum, Peter J. van der Spek, Bart Janssen, Eric Caldenhoven, Christian Rausch, Mark de Jong, Andrew P. Stubbs, Gerrit A. Meijer, Remond J.A. Fijneman, Guido Jenster","abstract":"The dataset \"Prostate Cancer and Normal Adjacent Prostate RNA-seq samples, NGS-ProToCol\" includes 41 Normal Adjacent Prostate and 51 ribo-depleted Prostate Cancer RNA-seq samples.\n----\nDetection of fusion transcripts and their genomic breakpoints from RNA sequencing data\nYouri Hoogstrate, Malgorzata A. Komor, René Böttcher, Job van Riet, Harmen J. G. van de Werken, Stef van Lieshout, Ralf Hoffmann, Evert van den Broek, Anne S. Bolijn, Natasja Dits, Daoud Sie, David van der Meer, Floor Pepers, Chris H. Bangma, Geert J. L. H. van Leenders, Marcel Smid, Pim French, John W.M. Martens, Wilbert van Workum, Peter J. van der Spek, Bart Janssen, Eric Caldenhoven, Christian Rausch, Mark de Jong, Andrew P. Stubbs, Gerrit A. Meijer, Remond J.A. Fijneman, Guido Jenster","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-25T13:58:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002817","title":"PAGE___Prenatal_Assessment_of_Genomes_and_Exomes__WGS_","description":"The Prenatal Assessment of Genomes and Exomes (PAGE) study is a multicentre prospective trial, performing exome sequence analysis on samples from 1000 families with structural anomalies in prenatal ultrasound screening but normal aneuploidy results, at least 22 families will also be analysed by whole genome sequencing.  The data will enable discovery of novel genetic disorders and increase the diagnostic yield.  Where appropriate, results will be reported back to the families at the end of the pregnancy, after thorough clinical review.  Ultimately, the translation of the acquired know-how into cost-effective prenatal diagnostic sequencing will improve genetics-derived prognoses and allow more informed parental counselling as well as management of pregnancy and childbirth.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The Prenatal Assessment of Genomes and Exomes (PAGE) study is a multicentre prospective trial, performing exome sequence analysis on samples from 1000 families with structural anomalies in prenatal ultrasound screening but normal aneuploidy results, at least 22 families will also be analysed by whole genome sequencing.  The data will enable discovery of novel genetic disorders and increase the diagnostic yield.  Where appropriate, results will be reported back to the families at the end of the pregnancy, after thorough clinical review.  Ultimately, the translation of the acquired know-how into cost-effective prenatal diagnostic sequencing will improve genetics-derived prognoses and allow more informed parental counselling as well as management of pregnancy and childbirth.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002818","title":"Whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes","description":"We carried out whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes. This study aimed to reveal the selective accumulation of rare variants in the coding and the UTR sequences within the genes of suicide victims. We also analysed the potential effect of STR and CNV variations, as well as the infection of the brain with neurovirulent viruses in this behavioural disorder. As a result, we have identified several candidate genes, among others three calcium channel genes that may potentially contribute to completed suicide. We also explored the potential implication of the TGF-β signalling pathway in the pathogenesis of suicidal behaviour. To our best knowledge, this is the first study that uses whole-exome sequencing for the investigation of suicide.","abstract":"We carried out whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes. This study aimed to reveal the selective accumulation of rare variants in the coding and the UTR sequences within the genes of suicide victims. We also analysed the potential effect of STR and CNV variations, as well as the infection of the brain with neurovirulent viruses in this behavioural disorder. As a result, we have identified several candidate genes, among others three calcium channel genes that may potentially contribute to completed suicide. We also explored the potential implication of the TGF-β signalling pathway in the pathogenesis of suicidal behaviour. To our best knowledge, this is the first study that uses whole-exome sequencing for the investigation of suicide.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-26T07:01:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002819","title":"2014_AML_WES_51 samples","description":"2014 AML WES study contains 51 paired WES samples which were collected from SNUH. The study was designed to examine the molecular abnormalities from leukemic patients at initial diagnosis in comparison with corresponding germ line control (saliva samples). The results of WXS were analyzed by Mutect for ranking cancer variants and creating mutational matrix.","abstract":"2014 AML WES study contains 51 paired WES samples which were collected from SNUH. The study was designed to examine the molecular abnormalities from leukemic patients at initial diagnosis in comparison with corresponding germ line control (saliva samples). The results of WXS were analyzed by Mutect for ranking cancer variants and creating mutational matrix.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-26T07:23:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002820","title":"Molecular subtypes of malignant peritoneal mesothelioma","description":"Malignant Peritoneal Mesothelioma (PeM) is a rare but frequently fatal cancer that originates from the peritoneal lining of the abdomen. Standard treatment of PeM is limited to cytoreductive surgery and/or chemotherapy, and no targeted therapies for PeM yet exist. This study performs comprehensive integrative analysis of genome, transcriptome, and proteome of treatment-naive PeM tumors with the aim of identifying mesothelioma-related molecular alterations and potentially identifying novel treatment strategies.","abstract":"Malignant Peritoneal Mesothelioma (PeM) is a rare but frequently fatal cancer that originates from the peritoneal lining of the abdomen. Standard treatment of PeM is limited to cytoreductive surgery and/or chemotherapy, and no targeted therapies for PeM yet exist. This study performs comprehensive integrative analysis of genome, transcriptome, and proteome of treatment-naive PeM tumors with the aim of identifying mesothelioma-related molecular alterations and potentially identifying novel treatment strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-27T08:05:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002821","title":"Single_cell_characterization_of_human_intestinal_organoids","description":"The aim of this study is to characterize  human intestinal organoids produced from human iPSCs. Different time points will be collected to deconvolute the transcriptional regulation of this process in vitro\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The aim of this study is to perform single cell RNA-seq on the 10X Chromium platform of human intestinal organoids produced from human iPSCs. Different time points will be collected to understand the transcriptional regulation of this process in vitro and the key transcriptional regulators involved in","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002822","title":"Psoriatic_arthritis_WGS","description":"Whole genome sequencing of  immune cells from patients diagnosed with psoriatic arthritis","abstract":"Whole genome sequencing of  immune cells from patients diagnosed with psoriatic arthritis","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-29T15:57:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002823","title":"Physiological and genetic adaptations to diving in Sea Nomads","description":"Understanding the physiology and genetics of human hypoxia tolerance has important medical implications, but this phenomenon has thus far only been investigated in high-altitude human populations. Another system, yet to be explored, is humans who engage in breath-hold diving. The indigenous Bajau people (“Sea Nomads”) of Southeast Asia live a subsistence lifestyle based on breath-hold diving and are renowned for their extraordinary breath holding abilities. However, it is unknown whether this has a genetic basis. Using a comparative genomic study, we show that natural selection on genetic variants in the PDE10A gene have increased spleen size in the Bajau, providing them with a larger reservoir of oxygenated red blood cells. We also find evidence of strong natural selection specific to the Bajau on BDKRB2, a gene affecting the human diving reflex. Thus, the Bajau, and possibly other natural diving populations, provide a new opportunity to study human adaptation to hypoxia tolerance.","abstract":"Understanding the physiology and genetics of human hypoxia tolerance has important medical implications, but this phenomenon has thus far only been investigated in high-altitude human populations. Another system, yet to be explored, is humans who engage in breath-hold diving. The indigenous Bajau people (“Sea Nomads”) of Southeast Asia live a subsistence lifestyle based on breath-hold diving and are renowned for their extraordinary breath holding abilities. However, it is unknown whether this has a genetic basis. Using a comparative genomic study, we show that natural selection on genetic variants in the PDE10A gene have increased spleen size in the Bajau, providing them with a larger reservoir of oxygenated red blood cells. We also find evidence of strong natural selection specific to the Bajau on BDKRB2, a gene affecting the human diving reflex. Thus, the Bajau, and possibly other natural diving populations, provide a new opportunity to study human adaptation to hypoxia tolerance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-29T18:09:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002824","title":"Test case to develop SOP","description":"Test case to develop SOP","abstract":"Test case to develop SOP","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002825","title":"Whole genome and whole exome sequencing of epilaptic patients","description":"In this project, we aim to identify genetic changes that predispose to epilepsy and those that predict the response to various anti-epileptic drugs. We sequenced whole genomes and whole exomes of epileptic individuals with different range of response to anti-epileptic drugs, and their relatives.","abstract":"In this project, we aim to identify genetic changes that predispose to epilepsy and those that predict the response to various anti-epileptic drugs. We sequenced whole genomes and whole exomes of epileptic individuals with different range of response to anti-epileptic drugs, and their relatives.","study_type":"Other","pubmed_ids":[29649218],"external_links":null,"is_released":true,"released_date":"2018-01-29T21:16:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002826","title":"A novel subset of human CD33+ haematopoietic stem cells characterized at single-cell resolution","description":"Elucidation of the identity and diversity of mechanisms that sustain long-term human blood cell production remains an important challenge. Previous studies indicate that, in adult mice, this property is ultimately vested in cells uniquely identified by their ability to clonally regenerate detectable levels of mature blood cells in serially transplanted recipients. We now present a combined multi-parameter analysis of the molecular features of very primitive human cord blood cells that display different cell output activities in vitro and in vivo. These analyses identified a new, prospectively separable, but still functionally heterogeneous, subset of long-term human blood-forming cells. Single-cell measurements of their transcriptional, DNA methylation and 40-protein content and of closely related phenotypes revealed numerous subtle, but consistent differences both within and between each subset analyzed. These results suggest that multiple regulatory mechanisms underlie the functional heterogeneity exhibited by clonally tracked human blood cell precursors with long-term output abilities.","abstract":"Elucidation of the identity and diversity of mechanisms that sustain long-term human blood cell production remains an important challenge. Previous studies indicate that, in adult mice, this property is ultimately vested in cells uniquely identified by their ability to clonally regenerate detectable levels of mature blood cells in serially transplanted recipients. We now present a combined multi-parameter analysis of the molecular features of very primitive human cord blood cells that display different cell output activities in vitro and in vivo. These analyses identified a new, prospectively separable, but still functionally heterogeneous, subset of long-term human blood-forming cells. Single-cell measurements of their transcriptional, DNA methylation and 40-protein content and of closely related phenotypes revealed numerous subtle, but consistent differences both within and between each subset analyzed. These results suggest that multiple regulatory mechanisms underlie the functional heterogeneity exhibited by clonally tracked human blood cell precursors with long-term output abilities.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-31T00:47:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002827","title":"Ibrutinib induces a global chromatin reorganisation in chronic lymphocytic leukaemia","description":"Chronic lymphocytic leukaemia (CLL) is the most common haematological malignancy in developed countries. Ibrutinib (PCI-32765), a specific and irreversible inhibitor of Bruton's Tyrosine Kinase (BTK) represents a major step forward in the treatment of CLL. We have undertaken a detailed analysis of the changes happening to the chromatin structure in CLL cells from patients continuously receiving oral doses of ibrutinib. ChIP-seq has been performed for H3K4me3, H3K27ac, H3K27me3 and EZH2 . We observed that Ibrutinib-dependent lymphocytosis correlates with a global and transient recruitment of EZH2 to active cis-regulatory elements and increased H3K27me3.","abstract":"Chronic lymphocytic leukaemia (CLL) is the most common haematological malignancy in developed countries. Ibrutinib (PCI-32765), a specific and irreversible inhibitor of Bruton's Tyrosine Kinase (BTK) represents a major step forward in the treatment of CLL. We have undertaken a detailed analysis of the changes happening to the chromatin structure in CLL cells from patients continuously receiving oral doses of ibrutinib. ChIP-seq has been performed for H3K4me3, H3K27ac, H3K27me3 and EZH2 . We observed that Ibrutinib-dependent lymphocytosis correlates with a global and transient recruitment of EZH2 to active cis-regulatory elements and increased H3K27me3.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-01-31T11:24:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002828","title":"Neoadjuvant Chemotherapy with and without Bevacizumab in Breast Cancer","description":"Material was collected from women with breast cancer included in a randomized phase II trial evaluating the efficacy and safety of bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) in combination with neoadjuvant treatment regimens. The inclusion criteria were met by patients with large (&gt; 2.5 cm) Her2 negative tumors, with no signs of metastatic disease who had not received any previous treatment. Written informed consent forms were obtained from all patients. The study was approved by the institutional protocol review board, the regional ethics committee, the Norwegian Medicines Agency and was carried out in accordance with the Declaration of Helsinki, International Conference on Harmony/Good Clinical practice. The study was registered in the http://www.ClinicalTrials.gov/ database with the identifier NCT00773695.Women in both treatment arms of the study received four cycles of FEC100 (5FU 600mg/m2, epirubicine 100 mg/m2 and cyclophosphamide 600mg/m2) given every three weeks, followed by 12 weekly infusions with paclitaxel (80 mg/m2) or four cycles with docetaxel (100 mg/m2), one every three weeks. Patients randomly assigned to the bevacizumab treatment arm received a 15 mg/kg dose on day one of each chemotherapy course, or a 10 mg/kg dose every other week when receiving paclitaxel. In a separate cohort of the study, a small subset of patients above 55 years of age and with hormone receptor positive tumors were treated with aromatase inhibitors (n = 12). The randomization to bevacizumab in this cohort were independent from the cohort receiving chemotherapy. In this study, only the patients who received chemotherapy with or without bevacizumab were included in the analyses.Tumor tissue was obtained by ultrasound guided 14- or 16-gauge needle biopsy prior to treatment and after 12 weeks of treatment. The third biopsy was taken at the time of surgery (week 25). Surgery was performed four weeks after administration of the last dose of bevacizumab. Biopsies from all three time points were frozen in liquid nitrogen and stored at -70°C. If possible, peripheral blood was also obtained at all three time points.Patients were classified as having pathological complete response (pCR) or non-pCR. Pathological complete response was obtained if there were no tumor cells detected in the surgery specimen, nor lymph nodes. Shrinkage of the tumor was measured and a continuous response ratio was calculated as the tumor size at surgery divided by tumor size at diagnosis. The tumor size before treatment start and at 12 weeks were measured by MRI, ultrasound or mammography. MRI was measurements were used for tumor classification and for the evaluations performed in the majority of patients. In 22 patients, MRI was not available, and the largest measured diameter of either ultrasound or mammography was used. Patients were categorized as having good, intermediate or no response (GR, IR, NR) based on percentage shrinkage (0-10%, 10-90% or more than 90% of the tumor left, respectively).Patients treated only with chemotherapy were classified as belonging to the Chemotherapy-arm, while patients treated with combination of chemotherapy and bevacizumab were classified within the Combination-arm.","abstract":"Material was collected from women with breast cancer included in a randomized phase II trial evaluating the efficacy and safety of bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) in combination with neoadjuvant treatment regimens. The inclusion criteria were met by patients with large (&gt; 2.5 cm) Her2 negative tumors, with no signs of metastatic disease who had not received any previous treatment. Written informed consent forms were obtained from all patients. The study was approved by the institutional protocol review board, the regional ethics committee, the Norwegian Medicines Agency and was carried out in accordance with the Declaration of Helsinki, International Conference on Harmony/Good Clinical practice. The study was registered in the http://www.ClinicalTrials.gov/ database with the identifier NCT00773695.Women in both treatment arms of the study received four cycles of FEC100 (5FU 600mg/m2, epirubicine 100 mg/m2 and cyclophosphamide 600mg/m2) given every three weeks, followed by 12 weekly infusions with paclitaxel (80 mg/m2) or four cycles with docetaxel (100 mg/m2), one every three weeks. Patients randomly assigned to the bevacizumab treatment arm received a 15 mg/kg dose on day one of each chemotherapy course, or a 10 mg/kg dose every other week when receiving paclitaxel. In a separate cohort of the study, a small subset of patients above 55 years of age and with hormone receptor positive tumors were treated with aromatase inhibitors (n = 12). The randomization to bevacizumab in this cohort were independent from the cohort receiving chemotherapy. In this study, only the patients who received chemotherapy with or without bevacizumab were included in the analyses.Tumor tissue was obtained by ultrasound guided 14- or 16-gauge needle biopsy prior to treatment and after 12 weeks of treatment. The third biopsy was taken at the time of surgery (week 25). Surgery was performed four weeks after administration of the last dose of bevacizumab. Biopsies from all three time points were frozen in liquid nitrogen and stored at -70°C. If possible, peripheral blood was also obtained at all three time points.Patients were classified as having pathological complete response (pCR) or non-pCR. Pathological complete response was obtained if there were no tumor cells detected in the surgery specimen, nor lymph nodes. Shrinkage of the tumor was measured and a continuous response ratio was calculated as the tumor size at surgery divided by tumor size at diagnosis. The tumor size before treatment start and at 12 weeks were measured by MRI, ultrasound or mammography. MRI was measurements were used for tumor classification and for the evaluations performed in the majority of patients. In 22 patients, MRI was not available, and the largest measured diameter of either ultrasound or mammography was used. Patients were categorized as having good, intermediate or no response (GR, IR, NR) based on percentage shrinkage (0-10%, 10-90% or more than 90% of the tumor left, respectively).Patients treated only with chemotherapy were classified as belonging to the Chemotherapy-arm, while patients treated with combination of chemotherapy and bevacizumab were classified within the Combination-arm.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002829","title":"Microsatellite_Instability_Breast_Cancer","description":"This project will investigate signatures and mutation patterns that have been identified in cancers with microsatellite instability due to defects in mismatch repair.","abstract":"This project will investigate signatures and mutation patterns that have been identified in cancers with microsatellite instability due to defects in mismatch repair.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002830","title":"Single cell sequencing reveals the origin and the order of mutation acquisition in T-cell acute lymphoblastic leukemia.","description":"Next-generation sequencing has provided a detailed overview of the various genomic lesions implicated in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL). Typically, 10 to 20 genomic lesions are found in T-ALL cells at diagnosis. However, it is currently unclear in which order these mutations are acquired and in which progenitor cells this is initiated. To address these questions, we used targeted single-cell sequencing of total bone marrow cells and CD34+CD38- multipotent progenitor cells for 4 T-ALL cases. Hierarchical clustering detected a dominant leukemia clone at diagnosis, accompanied by a few subclones harboring only a fraction of the mutations. We developed a graph-based algorithm to determine the order of mutation acquisition. Two of the four patients had an early event in a known oncogene (MED12, STAT5B) amongst various pre-leukemic events. Intermediate events included loss of 9p21 (CDKN2A/B) and acquisition of fusion genes, while NOTCH1 mutations were typically late events. Analysis of CD34+CD38- cells and myeloid progenitors revealed that in half of the cases somatic mutations were detectable in multipotent progenitor cells. We demonstrate that targeted single cell sequencing can elucidate the order of mutation acquisition in T-ALL and that T-ALL development can start in a multipotent progenitor cell.","abstract":"Next-generation sequencing has provided a detailed overview of the various genomic lesions implicated in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL). Typically, 10 to 20 genomic lesions are found in T-ALL cells at diagnosis. However, it is currently unclear in which order these mutations are acquired and in which progenitor cells this is initiated. To address these questions, we used targeted single-cell sequencing of total bone marrow cells and CD34+CD38- multipotent progenitor cells for 4 T-ALL cases. Hierarchical clustering detected a dominant leukemia clone at diagnosis, accompanied by a few subclones harboring only a fraction of the mutations. We developed a graph-based algorithm to determine the order of mutation acquisition. Two of the four patients had an early event in a known oncogene (MED12, STAT5B) amongst various pre-leukemic events. Intermediate events included loss of 9p21 (CDKN2A/B) and acquisition of fusion genes, while NOTCH1 mutations were typically late events. Analysis of CD34+CD38- cells and myeloid progenitors revealed that in half of the cases somatic mutations were detectable in multipotent progenitor cells. We demonstrate that targeted single cell sequencing can elucidate the order of mutation acquisition in T-ALL and that T-ALL development can start in a multipotent progenitor cell.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-05T09:44:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002831","title":"Size-tagged preferred ends in maternal plasma DNAshed light on the production mechanism and showutility in noninvasive prenatal testing","description":"Cell-free DNA molecules in the plasma of pregnant women exhibit nonrandom fragmentation with preferred end sites. We studied if such preferred end sites might bear any re- lationship with fragment lengths of plasma DNA. Short and long plasma DNA molecules were associated with different preferred DNA end sites. Analysis of size-tagged preferred ends could be used for measuring fetal DNA fraction and for facilitating fetal trisomy 21 detection. Fetal preferred end sites were generally located in the nucleosome cores, while the maternal ones were located in the linker regions. This con- ceptual framework provides an explanation of the relative shortness of fetal DNA in maternal plasma and brings us closer to understanding the biological mechanisms that influence plasma DNA fragmentation.","abstract":"Cell-free DNA molecules in the plasma of pregnant women exhibit nonrandom fragmentation with preferred end sites. We studied if such preferred end sites might bear any re- lationship with fragment lengths of plasma DNA. Short and long plasma DNA molecules were associated with different preferred DNA end sites. Analysis of size-tagged preferred ends could be used for measuring fetal DNA fraction and for facilitating fetal trisomy 21 detection. Fetal preferred end sites were generally located in the nucleosome cores, while the maternal ones were located in the linker regions. This con- ceptual framework provides an explanation of the relative shortness of fetal DNA in maternal plasma and brings us closer to understanding the biological mechanisms that influence plasma DNA fragmentation.","study_type":"Other","pubmed_ids":[29760053],"external_links":null,"is_released":true,"released_date":"2018-02-06T03:45:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002832","title":"Transcriptome profiling of human plucked frontal and occipital hair follicles","description":"Androgenetic alopecia (AGA) is characterized by a progressive and androgen-dependent loss of hair from the frontal and vertex regions of the scalp. Although large-scale genetic analyses have identified &gt;300 genetic risk factors, the underlying causal genes and pathways, and their involvement in core pathophysiological mechanisms, remain unclear. In the present study, systematic profiling of differential mRNA and microRNA expression was performed in human hair follicle samples from frontal and occipital scalp regions. Taken together, the present data improve understanding of the genomic regions, genes, and pathways that are implicated in AGA pathobiology.","abstract":"Androgenetic alopecia (AGA) is characterized by a progressive and androgen-dependent loss of hair from the frontal and vertex regions of the scalp. Although large-scale genetic analyses have identified &gt;300 genetic risk factors, the underlying causal genes and pathways, and their involvement in core pathophysiological mechanisms, remain unclear. In the present study, systematic profiling of differential mRNA and microRNA expression was performed in human hair follicle samples from frontal and occipital scalp regions. Taken together, the present data improve understanding of the genomic regions, genes, and pathways that are implicated in AGA pathobiology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-06T12:16:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002833","title":"Genomic profiling of ovarian adult type granulosa cell tumors","description":"To investigate the genomic landscape of primary and recurrent ovarian adult type granulosa cell tumors, we first identified an exploratory cohort comprised of cryopreserved surgical biopsies from 24 patients (primary, n = 8; recurrent, n = 16) with 20 having matched normal tissue or peripheral blood samples. We performed whole exome sequencing (WES) on these tumor samples at 200X target coverage (mean 226; range 165-296) and also performed WES on the available normal samples. In addition, we performed cancer gene panel sequencing using the T200.1 hybrid capture platform on FFPE tissue from 55 additional patients (primary, n = 27; recurrent, n = 28), of which we sequenced matched normal tissue for a total of 44.","abstract":"To investigate the genomic landscape of primary and recurrent ovarian adult type granulosa cell tumors, we first identified an exploratory cohort comprised of cryopreserved surgical biopsies from 24 patients (primary, n = 8; recurrent, n = 16) with 20 having matched normal tissue or peripheral blood samples. We performed whole exome sequencing (WES) on these tumor samples at 200X target coverage (mean 226; range 165-296) and also performed WES on the available normal samples. In addition, we performed cancer gene panel sequencing using the T200.1 hybrid capture platform on FFPE tissue from 55 additional patients (primary, n = 27; recurrent, n = 28), of which we sequenced matched normal tissue for a total of 44.","study_type":"Other","pubmed_ids":[29950560],"external_links":null,"is_released":true,"released_date":"2018-02-06T20:43:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002834","title":"Role_of_Cell_Division_during_Mesendoderm_formation___RNA_seq_analysis","description":"We have demonstrated that pluripotent stem cells divide two times during endoderm differentiation. The first division occur at about 20h after the induction of differentiation.  In order to determine whether this cell division is couple to the epigenetic changes that take place during this differentiation process, we carried out ChIP-seq experiments for two histone marks widely known for their role in specification of active and inactive gene promoter enhancers (H3K27Ac and H3K4me1). These experiments are accompanied by RNA seq analysis.\nTo this end, we conducted the following: H9 cells were synchronized in G2/M and then differentiated into endoderm for 24h, in presence or absence of different agents capable of blocking cells in specific phases of the cell cycle (Hydroxyurea: S-phase; Nocodazole: G2/M phase). Cells were collected at different time points. 12h after differentiation: Majority of the cells should be in S phase. In presence of Hidroxyurea (HU), cells should not live S phase and therefore, by the end of the experiment (24h-HU) those cells should still be in S phase; Nocodazole (Noc) was added after 12h of differentiation with the goal of blocking cells in the first G2/M phase during differentiation. Majority of these cells should be in G2/M by the end of the experiment (24h-Noc). Synchronized cells that differentiated normally in absence of these two drugs (E24h), will pass the first cell division, and be manly in G1/S phases of the cell cycle.","abstract":"We have demonstrated that pluripotent stem cells divide two times during endoderm differentiation. The first division occur at about 20h after the induction of differentiation.  In order to determine whether this cell division is couple to the epigenetic changes that take place during this differentiation process, we carried out ChIP-seq experiments for two histone marks widely known for their role in specification of active and inactive gene promoter enhancers (H3K27Ac and H3K4me1). These experiments are accompanied by RNA seq analysis.\nTo this end, we conducted the following: H9 cells were synchronized in G2/M and then differentiated into endoderm for 24h, in presence or absence of different agents capable of blocking cells in specific phases of the cell cycle (Hydroxyurea: S-phase; Nocodazole: G2/M phase). Cells were collected at different time points. 12h after differentiation: Majority of the cells should be in S phase. In presence of Hidroxyurea (HU), cells should not live S phase and therefore, by the end of the experiment (24h-HU) those cells should still be in S phase; Nocodazole (Noc) was added after 12h of differentiation with the goal of blocking cells in the first G2/M phase during differentiation. Majority of these cells should be in G2/M by the end of the experiment (24h-Noc). Synchronized cells that differentiated normally in absence of these two drugs (E24h), will pass the first cell division, and be manly in G1/S phases of the cell cycle.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002835","title":"RDviz dummy study","description":"RDviz dummy study - DO NOT RELEASE","abstract":"RDviz dummy study - DO NOT RELEASE","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002836","title":"DNA methylation using EPIC array in UK population study","description":"See www.understandingsociety.ac.uk","abstract":"See www.understandingsociety.ac.uk","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-07T14:17:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002837","title":"Heterozygosity mapping to localize dominant trait variants","description":"Inherited dominant pathogenic variants reside on a (possibly short) chromosome segment (haplotype) that has not experienced recombination. Marker variants in this segment tend to exhibit increased heterozygosity compared with variants elsewhere in the genome. The vcf files in this dataset contain whole-exome marker variants and pathogenic dominant variants with known chromosomal locations. Statistical approaches have been developed that exploit increased marker heterozygosity to approximately localize dominant trait variants. This dataset may be used to test these statistical approaches and to document the phenomenon of increased marker heterozygosity near inherited dominant pathogenic variants.","abstract":"Inherited dominant pathogenic variants reside on a (possibly short) chromosome segment (haplotype) that has not experienced recombination. Marker variants in this segment tend to exhibit increased heterozygosity compared with variants elsewhere in the genome. The vcf files in this dataset contain whole-exome marker variants and pathogenic dominant variants with known chromosomal locations. Statistical approaches have been developed that exploit increased marker heterozygosity to approximately localize dominant trait variants. This dataset may be used to test these statistical approaches and to document the phenomenon of increased marker heterozygosity near inherited dominant pathogenic variants.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002838","title":"Somatic alterations in pediatric cases with germline IKZF1 variants","description":"IKZF1, which encodes the lymphoid transcription factor IKAROS, is frequently targeted by somatic deletions and mutations in high-risk B-progenitor acute lymphoblastic leukemia (ALL) and is associated with poor prognosis. Somatic IKZF1 alterations result in the acquisition of stem cell-like features, overexpression of adhesion molecules causing aberrant cell-cell and cell-stroma interaction, and decreased sensitivity to tyrosine kinase inhibitors. In this study, we sought to comprehensively characterize germline IKZF1 genetic variation and to determine the extent to which they contribute to predisposition to ALL. We identified coding IKZF1 variation in familial childhood ALL and 1% of presumed sporadic B-ALL, with 28 unique germline IKZF1 variants in 45 children. The majority of variants adversely affected IKZF1 function and drug responsiveness of leukemic cells. Here, we report whole exome and RNA sequencing, and single nucleotide polymorphism array analysis, for all available patient samples to identify potential collaborating genetic events that were somatically acquired in our cohort of patients harboring germline IKZF1 variants.","abstract":"IKZF1, which encodes the lymphoid transcription factor IKAROS, is frequently targeted by somatic deletions and mutations in high-risk B-progenitor acute lymphoblastic leukemia (ALL) and is associated with poor prognosis. Somatic IKZF1 alterations result in the acquisition of stem cell-like features, overexpression of adhesion molecules causing aberrant cell-cell and cell-stroma interaction, and decreased sensitivity to tyrosine kinase inhibitors. In this study, we sought to comprehensively characterize germline IKZF1 genetic variation and to determine the extent to which they contribute to predisposition to ALL. We identified coding IKZF1 variation in familial childhood ALL and 1% of presumed sporadic B-ALL, with 28 unique germline IKZF1 variants in 45 children. The majority of variants adversely affected IKZF1 function and drug responsiveness of leukemic cells. Here, we report whole exome and RNA sequencing, and single nucleotide polymorphism array analysis, for all available patient samples to identify potential collaborating genetic events that were somatically acquired in our cohort of patients harboring germline IKZF1 variants.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002839","title":"The interface of malignant and immunologic clonal dynamics in high-grade serous ovarian cancer","description":"High-grade serous ovarian cancer exhibits extensive intratumoral heterogeneity coupled with widespread intraperitoneal disease. Despite this, metastatic spread of tumor clones is non-random, implying the existence of local microenvironmental factors that shape tumor progression. We interrogated the molecular interface between tumorinfiltrating lymphocytes (TIL) and cancer cells in 143 samples from 21 patients using whole-genome sequencing, immunohistochemistry, histologic image analysis, gene expression profiling, and T- and B-cell receptor sequencing. We identify 3 immunologic response categories, which frequently co-exist within individual patients. Furthermore, epithelial CD8+ TIL were inversely associated with malignant cell diversity, evidenced by subclonal neoepitope elimination and spatial tracking between tumor and T-cell clones. Intersecting mutational signatures and immune analysis showed that foldback inversion genomic aberrations lead to worse outcomes even in the presence of cytotoxic TIL (n=433). Thus, regional variation in immune contexture mirrors the pattern of intraperitoneal malignant spread, provoking new perspectives for treatment of this challenging disease.","abstract":"High-grade serous ovarian cancer exhibits extensive intratumoral heterogeneity coupled with widespread intraperitoneal disease. Despite this, metastatic spread of tumor clones is non-random, implying the existence of local microenvironmental factors that shape tumor progression. We interrogated the molecular interface between tumorinfiltrating lymphocytes (TIL) and cancer cells in 143 samples from 21 patients using whole-genome sequencing, immunohistochemistry, histologic image analysis, gene expression profiling, and T- and B-cell receptor sequencing. We identify 3 immunologic response categories, which frequently co-exist within individual patients. Furthermore, epithelial CD8+ TIL were inversely associated with malignant cell diversity, evidenced by subclonal neoepitope elimination and spatial tracking between tumor and T-cell clones. Intersecting mutational signatures and immune analysis showed that foldback inversion genomic aberrations lead to worse outcomes even in the presence of cytotoxic TIL (n=433). Thus, regional variation in immune contexture mirrors the pattern of intraperitoneal malignant spread, provoking new perspectives for treatment of this challenging disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-07T19:17:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002840","title":"A novel breast cancer cell line derived from a metastatic bone lesion of a breast cancer patient","description":"Purpose: We sought to generate and characterize a novel cell line from a breast cancer bone metastasis in order to better study the progression of the disease.Methods: The cell line, P7731, was derived from a metastatic bone lesion of a breast cancer patient and assessed for marker expression. P7731 was analyzed for DNA copy number variation, somatic mutations and gene expression and compared to the primary tumor. Results: P7731 cells are negative for estrogen receptor alpha (ERα), progesterone receptor (PR) and HER2 (triple-negative), strongly express vimentin (100% of cells positive) and also express cytokeratins 8/18 and 19 but at lower frequencies. Flow cytometry indicates P7731 cells are predominantly CD44+/CD49f+/EpCAM-, consistent with a primitive, mesenchymal-like phenotype. The cell line is tumorigenic in immunocompromised mice. Exome sequencing identified a total of 45 and 76 somatic mutations in the primary tumor and cell line respectively, of which 32 were identified in both samples and included mutations in known driver genes PIK3CA, TP53 and ARID1A. P7731 retains the DNA copy number alterations present in the matching primary tumor. Homozygous deletions detected in the cell line and in the primary tumor were found in regions containing three known (CDKN2A, CDKN2B and CDKN1B) and 23 putative tumor suppressor genes. Cell line specific gene amplification coupled with mRNA expression analysis revealed genes and pathways with potential pro-metastatic functions.Conclusion: This novel human breast cancer-bone metastasis cell line will be a useful model to study aspects of breast cancer biology, particularly metastasis-related changes from breast to bone.","abstract":"Purpose: We sought to generate and characterize a novel cell line from a breast cancer bone metastasis in order to better study the progression of the disease.Methods: The cell line, P7731, was derived from a metastatic bone lesion of a breast cancer patient and assessed for marker expression. P7731 was analyzed for DNA copy number variation, somatic mutations and gene expression and compared to the primary tumor. Results: P7731 cells are negative for estrogen receptor alpha (ERα), progesterone receptor (PR) and HER2 (triple-negative), strongly express vimentin (100% of cells positive) and also express cytokeratins 8/18 and 19 but at lower frequencies. Flow cytometry indicates P7731 cells are predominantly CD44+/CD49f+/EpCAM-, consistent with a primitive, mesenchymal-like phenotype. The cell line is tumorigenic in immunocompromised mice. Exome sequencing identified a total of 45 and 76 somatic mutations in the primary tumor and cell line respectively, of which 32 were identified in both samples and included mutations in known driver genes PIK3CA, TP53 and ARID1A. P7731 retains the DNA copy number alterations present in the matching primary tumor. Homozygous deletions detected in the cell line and in the primary tumor were found in regions containing three known (CDKN2A, CDKN2B and CDKN1B) and 23 putative tumor suppressor genes. Cell line specific gene amplification coupled with mRNA expression analysis revealed genes and pathways with potential pro-metastatic functions.Conclusion: This novel human breast cancer-bone metastasis cell line will be a useful model to study aspects of breast cancer biology, particularly metastasis-related changes from breast to bone.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-08T03:04:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002841","title":"BIR_Tandem_duplication","description":"This is a whole genome sequencing study on cell lines looking for structural variation.","abstract":"This is a whole genome sequencing study on cell lines looking for structural variation.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002842","title":"Somatic_mutation_and_clonal_evolution_in_the_human_bladder_WES","description":"In this study, we aim to characterise the landscape of mutation and clonal selection in the human bladder. The data in this study will be generated by whole-exome sequencing of laser-dissected microbiopsies from the bladder. The samples utilised in this study will include urothelium from transplant donors with no history of bladder cancer and cystectomy specimens from patients with bladder cancer.","abstract":"In this study, we aim to characterise the landscape of mutation and clonal selection in the human bladder. The data in this study will be generated by whole-exome sequencing of laser-dissected microbiopsies from the bladder. The samples utilised in this study will include urothelium from transplant donors with no history of bladder cancer and cystectomy specimens from patients with bladder cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-08T12:22:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002843","title":"Korean Lung Cancer - 36 pair WES data","description":"This study includes 36 paired samples of Korean Lung Cancer paitients.36 Lung Cnacer samples are paired with each normal(Saliva derived for control) sequencing data.The results of this WES study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.","abstract":"This study includes 36 paired samples of Korean Lung Cancer paitients.36 Lung Cnacer samples are paired with each normal(Saliva derived for control) sequencing data.The results of this WES study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-09T09:33:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002844","title":"2014_Lung_sq_WES","description":"Purpose Lung squamous cell carcinoma (SqCC) is the second most prevalent type of lung cancer. Currently, no targeted-therapeutics are approved for treatment of this cancer, largely due to lack of systematic understanding of the molecular parthenogenesis of the disease. To identify therapeutic targets and comparatively analyze them in lung SqCC, we probed somatic alterations of Korean lung SqCC.  Patients and Methods We performed massively parallel whole-exome sequencing of 104 Korean lung SqCC patients’ samples with matched normal samples. In addition, copy number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated.","abstract":"Purpose Lung squamous cell carcinoma (SqCC) is the second most prevalent type of lung cancer. Currently, no targeted-therapeutics are approved for treatment of this cancer, largely due to lack of systematic understanding of the molecular parthenogenesis of the disease. To identify therapeutic targets and comparatively analyze them in lung SqCC, we probed somatic alterations of Korean lung SqCC.  Patients and Methods We performed massively parallel whole-exome sequencing of 104 Korean lung SqCC patients’ samples with matched normal samples. In addition, copy number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-09T09:37:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002845","title":"Single cell sequencing of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis","description":"The quantity of tumor infiltrating lymphocytes (TILs) in breast cancer (BC) is a robust prognostic factor for improved patient survival particularly in triple negative and HER2-overexpressing BC subtypes. Whilst T cells are the predominant TIL population, the relationship between quantitative and qualitative differences in T cell subpopulations and patient prognosis remains unknown. We performed single-cell RNA sequencing (scRNA-seq) of 6311 T cells isolated from human BCs, and show for the first time that significant heterogeneity exists in the infiltrating T cell population. We demonstrated that high TIL BCs contained significant numbers of CD8+ T cells with features of tissue-resident memory T (TRM) cell differentiation and that these CD8+ TRM cells expressed high levels of immune checkpoint molecules and effector proteins. A CD8+ TRM gene signature developed from the scRNA-seq data was significantly associated with improved patient survival in early-stage triple negative breast cancer (TNBC) and provided better prognostication compared with CD8 expression alone. Our data suggests that CD8+ TRM contribute to BC immunosurveillance and are the key targets of modulation through immune checkpoint inhibition. Further understanding of the development, maintenance and regulation of TRM cells will be crucial for successful immunotherapeutic development in BC.","abstract":"The quantity of tumor infiltrating lymphocytes (TILs) in breast cancer (BC) is a robust prognostic factor for improved patient survival particularly in triple negative and HER2-overexpressing BC subtypes. Whilst T cells are the predominant TIL population, the relationship between quantitative and qualitative differences in T cell subpopulations and patient prognosis remains unknown. We performed single-cell RNA sequencing (scRNA-seq) of 6311 T cells isolated from human BCs, and show for the first time that significant heterogeneity exists in the infiltrating T cell population. We demonstrated that high TIL BCs contained significant numbers of CD8+ T cells with features of tissue-resident memory T (TRM) cell differentiation and that these CD8+ TRM cells expressed high levels of immune checkpoint molecules and effector proteins. A CD8+ TRM gene signature developed from the scRNA-seq data was significantly associated with improved patient survival in early-stage triple negative breast cancer (TNBC) and provided better prognostication compared with CD8 expression alone. Our data suggests that CD8+ TRM contribute to BC immunosurveillance and are the key targets of modulation through immune checkpoint inhibition. Further understanding of the development, maintenance and regulation of TRM cells will be crucial for successful immunotherapeutic development in BC.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-12T12:36:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002846","title":"Whole exome sequencing of longitudinal samples from a melanoma patient receiving MEK plus CDK4/6 inhibitor therapy.","description":"Combined MEK and CDK4/6 inhibition (MEKi+CDK4i) has shown promising clinical outcomes in NRAS mutant melanoma patients. Here, we interrogated longitudinal biopsies from a patient who initially responded to MEKi+CDK4i therapy but subsequently developed resistance. Whole exome sequencing and functional validation identified an acquired PIK3CAE545K mutation as conferring drug resistance. We demonstrate that PIK3CAE545K pre-existed in a rare subpopulation that was missed by both clinical and research testing, but was revealed upon multi-region sampling due to PIK3CAE545K being non-uniformly distributed. This resistant population rapidly expanded after the initiation of MEKi+CDK4i therapy and persisted in all successive samples even after immune checkpoint therapy and distant metastasis.  Functional studies identified activated S6K1 as both a key marker and specific therapeutic vulnerability downstream of PIK3CAE545K-induced resistance. These results demonstrate that comprehensive analysis of pre-treatment samples can reveal rare pre-existing resistant subpopulations and also posit S6K1 as a common downstream therapeutic nexus for the MAPK, CDK4/6, and PI3K pathways.","abstract":"Combined MEK and CDK4/6 inhibition (MEKi+CDK4i) has shown promising clinical outcomes in NRAS mutant melanoma patients. Here, we interrogated longitudinal biopsies from a patient who initially responded to MEKi+CDK4i therapy but subsequently developed resistance. Whole exome sequencing and functional validation identified an acquired PIK3CAE545K mutation as conferring drug resistance. We demonstrate that PIK3CAE545K pre-existed in a rare subpopulation that was missed by both clinical and research testing, but was revealed upon multi-region sampling due to PIK3CAE545K being non-uniformly distributed. This resistant population rapidly expanded after the initiation of MEKi+CDK4i therapy and persisted in all successive samples even after immune checkpoint therapy and distant metastasis.  Functional studies identified activated S6K1 as both a key marker and specific therapeutic vulnerability downstream of PIK3CAE545K-induced resistance. These results demonstrate that comprehensive analysis of pre-treatment samples can reveal rare pre-existing resistant subpopulations and also posit S6K1 as a common downstream therapeutic nexus for the MAPK, CDK4/6, and PI3K pathways.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-12T17:51:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002847","title":"ALPI deficiency and inflammatory bowel disease","description":"Inflammatory bowel diseases (IBDs) are complex and severe disorders ascribed to alterations in the dialogue between the microbiota and the host immune system (Bouma &amp; Strober, 2003; Maloy &amp; Powrie, 2011). By using whole‐exome sequencing (WES), we report the identification of compound heterozygous ALPI mutations in two unrelated patients displaying severe intestinal inflammation and autoimmunity. ALPI encodes the Intestinal alkaline phosphatase, a brush border metalloenzyme that catalyses phosphate hydrolysis of the lipid moiety of LPS and thereby drastically reduces LPS pro‐inflammatory activity (Schromm et al, 1998; Goldberg et al, 2008).","abstract":"Inflammatory bowel diseases (IBDs) are complex and severe disorders ascribed to alterations in the dialogue between the microbiota and the host immune system (Bouma &amp; Strober, 2003; Maloy &amp; Powrie, 2011). By using whole‐exome sequencing (WES), we report the identification of compound heterozygous ALPI mutations in two unrelated patients displaying severe intestinal inflammation and autoimmunity. ALPI encodes the Intestinal alkaline phosphatase, a brush border metalloenzyme that catalyses phosphate hydrolysis of the lipid moiety of LPS and thereby drastically reduces LPS pro‐inflammatory activity (Schromm et al, 1998; Goldberg et al, 2008).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-13T17:33:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002848","title":"A mouse model xenograft was developed from a patient with Head and Neck Squamous Cell Cancer and then treated by drugs targeting the PIK3CA pathway.","description":"Mutations and amplifications in the PIK3CA gene are some of the most frequently seen alterations in head and neck squamous cell cancer (HNSCC). This project study the effect of a leading clinical drug that specifically targets the gene product of PIK3CA. Although this drug works well in HNSCC, it is anticipated that some patients will become resistant to it over time and will stop responding, as this has been observed when other 'targeted' drugs are used in other cancers. The goal here is to determine what molecular mechanisms are involved with mediating resistance over time to the PIK3CA drug. The drug is called \"BYL719\". A mouse xenograft model was created in this effect. Basically, a tumour from a patient with HNSCC was engrafted in multiple mice, and once it grew, the mice were treated with BYL719 or a vehicle (corn oil). Over time, the corn oil mice's tumours grow very quickly. The BYL719-treated mice's tumours are static for about the first 50 days of treatment (suggesting the drug is quite effective), but then begin to resume growth (suggesting they have become resistant to the drug). With the tumours collected from the mice at the end point of the study, we are using a multi-platform approach to figure out what the differences are in the BYL719-resistant tumours, compared to the corn oil tumours, primary tumour (never engrafted into mice) and the patient blood.","abstract":"Mutations and amplifications in the PIK3CA gene are some of the most frequently seen alterations in head and neck squamous cell cancer (HNSCC). This project study the effect of a leading clinical drug that specifically targets the gene product of PIK3CA. Although this drug works well in HNSCC, it is anticipated that some patients will become resistant to it over time and will stop responding, as this has been observed when other 'targeted' drugs are used in other cancers. The goal here is to determine what molecular mechanisms are involved with mediating resistance over time to the PIK3CA drug. The drug is called \"BYL719\". A mouse xenograft model was created in this effect. Basically, a tumour from a patient with HNSCC was engrafted in multiple mice, and once it grew, the mice were treated with BYL719 or a vehicle (corn oil). Over time, the corn oil mice's tumours grow very quickly. The BYL719-treated mice's tumours are static for about the first 50 days of treatment (suggesting the drug is quite effective), but then begin to resume growth (suggesting they have become resistant to the drug). With the tumours collected from the mice at the end point of the study, we are using a multi-platform approach to figure out what the differences are in the BYL719-resistant tumours, compared to the corn oil tumours, primary tumour (never engrafted into mice) and the patient blood.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002849","title":"HSC_population_dynamics_KSP_samples___RNAseq","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Spontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002850","title":"A genomic approach towards an understanding of clonal evolution and disease progression in multiple myeloma","description":"Multiple Myeloma (MM) is a largely incurable haematological malignancy defined by the clonal proliferation of malignant plasma cells within the bone marrow. Clonal heterogeneity has recently been established as a feature in MM, however, the subclonal evolution associated with disease progression has not been described. We used whole exome sequencing to analyse 10 paired patient samples, providing new insights into the progression from Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smouldering MM (SMM), to symptomatic MM. We confirm that clonal heterogeneity is a common feature at diagnosis and that the driving events involved in disease progression are more complex than previously reported. While we observe some previously identified known “drivers” of MM, we find that the driving events involved in progression are complex and not limited to the known SNVs or CNVs. The RAS/MAPK pathway was found to be the most frequently deregulated pathway, with recurrent mutations in KRAS and NRAS observed in patients at both MGUS/SMM and MM stages. We reveal that MM evolution is mainly characterised by the phenomenon of clonal stability, where the subclonal plasma cell populations identified at MM progression are already present in the asymptomatic MGUS/SMM stages. These subclonal populations could be amenable to therapeutic intervention to arrest transformation to MM.","abstract":"Multiple Myeloma (MM) is a largely incurable haematological malignancy defined by the clonal proliferation of malignant plasma cells within the bone marrow. Clonal heterogeneity has recently been established as a feature in MM, however, the subclonal evolution associated with disease progression has not been described. We used whole exome sequencing to analyse 10 paired patient samples, providing new insights into the progression from Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smouldering MM (SMM), to symptomatic MM. We confirm that clonal heterogeneity is a common feature at diagnosis and that the driving events involved in disease progression are more complex than previously reported. While we observe some previously identified known “drivers” of MM, we find that the driving events involved in progression are complex and not limited to the known SNVs or CNVs. The RAS/MAPK pathway was found to be the most frequently deregulated pathway, with recurrent mutations in KRAS and NRAS observed in patients at both MGUS/SMM and MM stages. We reveal that MM evolution is mainly characterised by the phenomenon of clonal stability, where the subclonal plasma cell populations identified at MM progression are already present in the asymptomatic MGUS/SMM stages. These subclonal populations could be amenable to therapeutic intervention to arrest transformation to MM.","study_type":"Other","pubmed_ids":[28466550],"external_links":null,"is_released":true,"released_date":"2018-02-16T04:52:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002851","title":"Transcriptome sequencing of Gingivo-buccal Cancer : ICGC-India Project_YR03","description":"Transcriptome Sequencing of Gingivo-buccal Cancer: ICGC-India ProjectAs a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India.   There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection.  Transcriptome sequencing of paired RNA samples – isolated from the tumor and adjacent normal tissues of 12 patients – have been performed. Detailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from adjacent normal and tumor tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai.  Sequencing is being performed at the National Institute of Biomedical Genomics, Kalyani.","abstract":"Transcriptome Sequencing of Gingivo-buccal Cancer: ICGC-India ProjectAs a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India.   There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection.  Transcriptome sequencing of paired RNA samples – isolated from the tumor and adjacent normal tissues of 12 patients – have been performed. Detailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from adjacent normal and tumor tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai.  Sequencing is being performed at the National Institute of Biomedical Genomics, Kalyani.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-16T06:17:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002852","title":"Whole Exome sequencing of Gingivo-buccal Cancer : ICGC-India Project_Batch04","description":"Whole Exome Sequencing of Gingivo-buccal Cancer: ICGC-India ProjectAs a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India.   There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection.  Exome of paired DNA samples – isolated from the tumor tissue and from the blood of 47 patients – have been performed to catalog germline and somatic mutations. Association between each observed genomic alteration and exposure to environmental risk factors is being explored.\tDetailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from blood and tumor tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai.  Whole exome sequencing is being performed at the National Institute of Biomedical Genomics, Kalyani.","abstract":"Whole Exome Sequencing of Gingivo-buccal Cancer: ICGC-India ProjectAs a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India.   There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection.  Exome of paired DNA samples – isolated from the tumor tissue and from the blood of 47 patients – have been performed to catalog germline and somatic mutations. Association between each observed genomic alteration and exposure to environmental risk factors is being explored.\tDetailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from blood and tumor tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai.  Whole exome sequencing is being performed at the National Institute of Biomedical Genomics, Kalyani.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-16T07:05:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002853","title":"Genomic and functional fidelity of small cell lung cancer patient-derived xenografts","description":"Small cell lung cancer (SCLC) patient-derived xenografts (PDXs) can be generated from biopsies or circulating tumor cells (CTCs), though scarcity of tissue and low efficiency of tumor growth have previously limited these approaches. Applying an established clinical-translational pipeline for tissue collection and an automated microfluidic platform for CTC-enrichment, we generated 17 biopsy-derived PDXs and 17 CTC-derived PDXs in a two-year timeframe, at efficiencies of 89% and 38%, respectively. Whole exome sequencing showed that somatic alterations are stably maintained between patient tumors and PDXs. Early-passage PDXs maintain the genomic and transcriptional profiles of the founder PDX. In vivo treatment with etoposide and cisplatin (EP) in 30 PDX models demonstrated greater sensitivity in PDXs from EP naïve patients, and resistance to EP corresponded to increased expression of a MYC gene signature. Finally, serial CTC-derived PDXs generated from an individual patient at multiple time points accurately recapitulated the evolving drug sensitivities of that patient’s disease. Collectively, this work highlights the translational potential of this strategy.","abstract":"Small cell lung cancer (SCLC) patient-derived xenografts (PDXs) can be generated from biopsies or circulating tumor cells (CTCs), though scarcity of tissue and low efficiency of tumor growth have previously limited these approaches. Applying an established clinical-translational pipeline for tissue collection and an automated microfluidic platform for CTC-enrichment, we generated 17 biopsy-derived PDXs and 17 CTC-derived PDXs in a two-year timeframe, at efficiencies of 89% and 38%, respectively. Whole exome sequencing showed that somatic alterations are stably maintained between patient tumors and PDXs. Early-passage PDXs maintain the genomic and transcriptional profiles of the founder PDX. In vivo treatment with etoposide and cisplatin (EP) in 30 PDX models demonstrated greater sensitivity in PDXs from EP naïve patients, and resistance to EP corresponded to increased expression of a MYC gene signature. Finally, serial CTC-derived PDXs generated from an individual patient at multiple time points accurately recapitulated the evolving drug sensitivities of that patient’s disease. Collectively, this work highlights the translational potential of this strategy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-16T08:46:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002854","title":"Colorectal adenomas, carcinomas and adjacent normal NKI-AvL TGO series NGS-ProToCol","description":"Cancer is caused by changes in the genome of cells, resulting in aberrant transcripts and proteins. In order to understand why normal cells become cancer cells and how we can identify and destroy them, the CTMM-NGS-ProToCol project aimed to understand prostate and colorectal cancer through DNA and RNA molecular profiling, to further improve diagnosis, prognosis and treatment.The state-of-the-art within the field of genome sequencing makes it possible to identify all the modifications in our genome that encode for RNA and of the transcripts themselves. The latest development in RNA sequencing is that if one does not select for polyA RNA, but first removes rRNA from the total RNA and then performs ‘random’ RNA sequencing, 30-60% of the reads are intronic. Since about 40% of the genome consists of genes (and only 1.6% is exonic), deep RNA sequencing will cover not only the exons, but also a large portion of the introns and therefore much of the genome. The power of the combined sequencing of genome and transcriptome is the full view of copy number aberrations (CNA), exon mutations and the consequence and relevance of the mutations at the RNA level in the form of differential gene expression, alternative splicing, alternative promoter usage, novel transcripts, fusion transcripts, read-through transcripts and mutations. For the colorectal (tumor) tissue dataset, we applied molecular profiling to 30 colorectal adenomas, 30 colorectal carcinomas and 18 normal adjacent colon tissues.","abstract":"Cancer is caused by changes in the genome of cells, resulting in aberrant transcripts and proteins. In order to understand why normal cells become cancer cells and how we can identify and destroy them, the CTMM-NGS-ProToCol project aimed to understand prostate and colorectal cancer through DNA and RNA molecular profiling, to further improve diagnosis, prognosis and treatment.The state-of-the-art within the field of genome sequencing makes it possible to identify all the modifications in our genome that encode for RNA and of the transcripts themselves. The latest development in RNA sequencing is that if one does not select for polyA RNA, but first removes rRNA from the total RNA and then performs ‘random’ RNA sequencing, 30-60% of the reads are intronic. Since about 40% of the genome consists of genes (and only 1.6% is exonic), deep RNA sequencing will cover not only the exons, but also a large portion of the introns and therefore much of the genome. The power of the combined sequencing of genome and transcriptome is the full view of copy number aberrations (CNA), exon mutations and the consequence and relevance of the mutations at the RNA level in the form of differential gene expression, alternative splicing, alternative promoter usage, novel transcripts, fusion transcripts, read-through transcripts and mutations. For the colorectal (tumor) tissue dataset, we applied molecular profiling to 30 colorectal adenomas, 30 colorectal carcinomas and 18 normal adjacent colon tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-16T12:28:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002855","title":"Human_Evolution_3D","description":"Whole genome sequencing and phasing of 7 individuals with Aboriginal Australian ancestry using the 10x Genomics Chromium platform. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Whole genome sequencing and phasing of 7 individuals with Aboriginal Australian ancestry using the 10x Genomics Chromium platform.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002856","title":"Integrated analysis of relapsed B-cell precursor Acute Lymphoblastic Leukemia identifies subtype-specific cytokine and metabolic signatures","description":"Recent efforts reclassified B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) into more refined subtypes. Nevertheless, outcomes of relapsed BCP-ALL remain unsatisfactory, particularly in adult patients where the molecular basis of relapse is still poorly understood. To elucidate the evolution of relapse in BCP-ALL, we established a comprehensive multi-omics dataset including DNA-sequencing, RNA-sequencing, DNA methylation array and proteome MASS-spec data from matched diagnosis and relapse samples of BCP-ALL patients (n = 50) including the subtypes DUX4, Ph-like and two aneuploid subtypes. Relapse-specific alterations were enriched for chromatin modifiers, nucleotide and steroid metabolism including the novel candidates FPGS, AGBL and ZNF483. The proteome expression analysis unraveled deregulation of metabolic pathways at relapse including the key proteins G6PD, TKT, GPI and PGD. Moreover, we identified a novel relapse-specific gene signature specific for DUX4 BCP-ALL patients highlighting chemotaxis and cytokine environment as a possible driver event at relapse. This study presents novel insights at distinct molecular levels of relapsed BCP-ALL based on a comprehensive multi-omics integrated data set including a valuable proteomics data set. The relapse specific aberrations reveal metabolic signatures on genomic and proteomic levels in BCP-ALL relapse. Furthermore, the chemokine expression signature in DUX4 relapse underscores the distinct status of DUX4-fusion BCP-ALL.","abstract":"Recent efforts reclassified B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) into more refined subtypes. Nevertheless, outcomes of relapsed BCP-ALL remain unsatisfactory, particularly in adult patients where the molecular basis of relapse is still poorly understood. To elucidate the evolution of relapse in BCP-ALL, we established a comprehensive multi-omics dataset including DNA-sequencing, RNA-sequencing, DNA methylation array and proteome MASS-spec data from matched diagnosis and relapse samples of BCP-ALL patients (n = 50) including the subtypes DUX4, Ph-like and two aneuploid subtypes. Relapse-specific alterations were enriched for chromatin modifiers, nucleotide and steroid metabolism including the novel candidates FPGS, AGBL and ZNF483. The proteome expression analysis unraveled deregulation of metabolic pathways at relapse including the key proteins G6PD, TKT, GPI and PGD. Moreover, we identified a novel relapse-specific gene signature specific for DUX4 BCP-ALL patients highlighting chemotaxis and cytokine environment as a possible driver event at relapse. This study presents novel insights at distinct molecular levels of relapsed BCP-ALL based on a comprehensive multi-omics integrated data set including a valuable proteomics data set. The relapse specific aberrations reveal metabolic signatures on genomic and proteomic levels in BCP-ALL relapse. Furthermore, the chemokine expression signature in DUX4 relapse underscores the distinct status of DUX4-fusion BCP-ALL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-16T14:41:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002857","title":"Somatic_mutation_and_clonal_evolution_normal_breast_tissue_WGS","description":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;70 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumour development.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;70 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumour development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-16T16:20:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002858","title":"Somatic_mutation_and_clonal_evolution_normal_breast_tissue_TGS","description":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;70 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumour development.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;70 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumour development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-16T16:23:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002859","title":"Targeted panel data for newly diagnosed myeloma patients.","description":"Genomic abnormalities in MM are common and can affect a patients outcome.  Here we have performed targeted sequencing on xx patient tumor samples and matched control DNA. The targeted panel consists of ~160 genes and copy number regions, as well as key regions of chromosomal translocation including IGH, IGK, IGL and MYC.  Using mutation, copy number, and translocation information we have been able to identify abnormalities that affect prognosis including bi-allelic inactivation of TP53 and rearrangements involving MYC.","abstract":"Genomic abnormalities in MM are common and can affect a patients outcome.  Here we have performed targeted sequencing on xx patient tumor samples and matched control DNA. The targeted panel consists of ~160 genes and copy number regions, as well as key regions of chromosomal translocation including IGH, IGK, IGL and MYC.  Using mutation, copy number, and translocation information we have been able to identify abnormalities that affect prognosis including bi-allelic inactivation of TP53 and rearrangements involving MYC.","study_type":"Other","pubmed_ids":[28550191],"external_links":null,"is_released":true,"released_date":"2018-02-16T16:24:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002860","title":"Whole-genome and transcriptome sequencing of tumor-stage mycosis fungoides","description":"Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL), a group of malignancies derived from skin-homing malignant T cells. We subjected tumor biopsies from MF patients to whole-genome sequencing and RNA-sequencing to investigate genomic alterations and deregulated gene expression in the disease.","abstract":"Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL), a group of malignancies derived from skin-homing malignant T cells. We subjected tumor biopsies from MF patients to whole-genome sequencing and RNA-sequencing to investigate genomic alterations and deregulated gene expression in the disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-19T09:17:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002861","title":"Investigating_the_impact_of_MBD4_on_the_mutability_of_the_germline","description":"We will be testing the hypothesis that MBD4 PTV germline carriers also show an increased number of C toT germline mutations in their offspring. \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We will be testing the hypothesis that MBD4 PTV germline carriers also show an increased number of C toT germline mutations in their offspring.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-20T11:47:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002862","title":"Small_molecule_inhibitors_in_melanoma___Kenski___Kong___RNAseq","description":"Small-molecule inhibitors targeting the most commonly activated pathway in melanoma, MAPK pathway (either alone or in combination) are already given to melanoma patients for few years, and initially reduce tumour burden dramatically, eventually melanomas become resistant and tumours progress while on treatment. Resistance to this treatment occurs by acquisition of additional mutations or other alterations that affect the mitogen-activated protein kinase (MAPK) pathway by either direct or indirect signalling. Many resistance mechanisms somehow lead to reactivation of extracellular signal-regulated kinase (ERK), thereby restoring signalling of the oncogenic BRAF/MEK/ERK pathway. In addition, PI3K pathway activation contributes to resistance to BRAF inhibition. Less frequent but equally important to the phenomenon of targeted drug resistance is the observation that B15–20% of BRAF mutant melanoma patients fail to respond to BRAF inhibition already early on treatment, owing to intrinsic resistance. These patients have little therapeutic options, unless immunotherapy can be given. To better understand the resistance mechanisms in MAPK inhibitor-treated melanoma patients and melanoma biology, our lab generated a big panel of MAPK inhibitor resistant melanoma cell lines by continuous drug exposure. The understanding of the genetic landscape and gene expression as well as cross resistance to other treatment regimens, and other aspects of melanoma biology such as phenotype switch, will allow us to better exploit new therapeutic strategies for melanoma patients.","abstract":"Small-molecule inhibitors targeting the most commonly activated pathway in melanoma, MAPK pathway (either alone or in combination) are already given to melanoma patients for few years, and initially reduce tumour burden dramatically, eventually melanomas become resistant and tumours progress while on treatment. Resistance to this treatment occurs by acquisition of additional mutations or other alterations that affect the mitogen-activated protein kinase (MAPK) pathway by either direct or indirect signalling. Many resistance mechanisms somehow lead to reactivation of extracellular signal-regulated kinase (ERK), thereby restoring signalling of the oncogenic BRAF/MEK/ERK pathway. In addition, PI3K pathway activation contributes to resistance to BRAF inhibition. Less frequent but equally important to the phenomenon of targeted drug resistance is the observation that B15–20% of BRAF mutant melanoma patients fail to respond to BRAF inhibition already early on treatment, owing to intrinsic resistance. These patients have little therapeutic options, unless immunotherapy can be given. To better understand the resistance mechanisms in MAPK inhibitor-treated melanoma patients and melanoma biology, our lab generated a big panel of MAPK inhibitor resistant melanoma cell lines by continuous drug exposure. The understanding of the genetic landscape and gene expression as well as cross resistance to other treatment regimens, and other aspects of melanoma biology such as phenotype switch, will allow us to better exploit new therapeutic strategies for melanoma patients.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002863","title":"Small_molecule_inhibitors_in_melanoma___Kenski___Kong___WES","description":"Small-molecule inhibitors targeting the most commonly activated pathway in melanoma, MAPK pathway (either alone or in combination) are already given to melanoma patients for few years, and initially reduce tumour burden dramatically, eventually melanomas become resistant and tumours progress while on treatment. Resistance to this treatment occurs by acquisition of additional mutations or other alterations that affect the mitogen-activated protein kinase (MAPK) pathway by either direct or indirect signalling. Many resistance mechanisms somehow lead to reactivation of extracellular signal-regulated kinase (ERK), thereby restoring signalling of the oncogenic BRAF/MEK/ERK pathway. In addition, PI3K pathway activation contributes to resistance to BRAF inhibition. Less frequent but equally important to the phenomenon of targeted drug resistance is the observation that B15–20% of BRAF mutant melanoma patients fail to respond to BRAF inhibition already early on treatment, owing to intrinsic resistance. These patients have little therapeutic options, unless immunotherapy can be given. To better understand the resistance mechanisms in MAPK inhibitor-treated melanoma patients and melanoma biology, our lab generated a big panel of MAPK inhibitor resistant melanoma cell lines by continuous drug exposure. The understanding of the genetic landscape and gene expression as well as cross resistance to other treatment regimens, and other aspects of melanoma biology such as phenotype switch, will allow us to better exploit new therapeutic strategies for melanoma patients.","abstract":"Small-molecule inhibitors targeting the most commonly activated pathway in melanoma, MAPK pathway (either alone or in combination) are already given to melanoma patients for few years, and initially reduce tumour burden dramatically, eventually melanomas become resistant and tumours progress while on treatment. Resistance to this treatment occurs by acquisition of additional mutations or other alterations that affect the mitogen-activated protein kinase (MAPK) pathway by either direct or indirect signalling. Many resistance mechanisms somehow lead to reactivation of extracellular signal-regulated kinase (ERK), thereby restoring signalling of the oncogenic BRAF/MEK/ERK pathway. In addition, PI3K pathway activation contributes to resistance to BRAF inhibition. Less frequent but equally important to the phenomenon of targeted drug resistance is the observation that B15–20% of BRAF mutant melanoma patients fail to respond to BRAF inhibition already early on treatment, owing to intrinsic resistance. These patients have little therapeutic options, unless immunotherapy can be given. To better understand the resistance mechanisms in MAPK inhibitor-treated melanoma patients and melanoma biology, our lab generated a big panel of MAPK inhibitor resistant melanoma cell lines by continuous drug exposure. The understanding of the genetic landscape and gene expression as well as cross resistance to other treatment regimens, and other aspects of melanoma biology such as phenotype switch, will allow us to better exploit new therapeutic strategies for melanoma patients.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-20T13:12:18+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002864","title":"Genome analysis of oesophageal cancer and Barrett's oesophagus","description":"The median survival of oesophageal cancer this year is only 13 to 19 months after diagnosis and more than 90% will die from their disease. Therefore better treatment options are needed. The likelihood of cure for early screen-detected cancers is much higher. Barrett's oesophagus is a pre-cancerous lesion associated with a 30-40 fold increased risk of developing cancer. In an attempt to detect cancer early many patients with Barrett's are enrolled into surveillance programs involving regular endoscopies. A major problem with this approach is that the prevalence of BO in the population is estimated to be around 2%, but most patients with BO will never develop cancer. We are undertaking genomic and/or transcriptomic analysis of oesophageal tumours, Barrett's oesophagus and matched normal samples. The aim is to identify oesophageal-related genomic and transcriptomic alterations, which may reveal mutational process occurring, suggest biomarkers of tumour progression and treatment and identify novel treatment strategies.","abstract":"The median survival of oesophageal cancer this year is only 13 to 19 months after diagnosis and more than 90% will die from their disease. Therefore better treatment options are needed. The likelihood of cure for early screen-detected cancers is much higher. Barrett's oesophagus is a pre-cancerous lesion associated with a 30-40 fold increased risk of developing cancer. In an attempt to detect cancer early many patients with Barrett's are enrolled into surveillance programs involving regular endoscopies. A major problem with this approach is that the prevalence of BO in the population is estimated to be around 2%, but most patients with BO will never develop cancer. We are undertaking genomic and/or transcriptomic analysis of oesophageal tumours, Barrett's oesophagus and matched normal samples. The aim is to identify oesophageal-related genomic and transcriptomic alterations, which may reveal mutational process occurring, suggest biomarkers of tumour progression and treatment and identify novel treatment strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-20T23:43:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002865","title":"Human Pancreatic Beta Cell lncRNAs Control Cell-Specific Regulatory Networks","description":"Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks.","abstract":"Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks.","study_type":"Other","pubmed_ids":[28041957],"external_links":null,"is_released":true,"released_date":"2018-02-21T10:34:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002866","title":"Exploring_the_heterogeneity_of_sarcoma_using_single_cell_sequencing_","description":"Multi region samples are collected from patients, with consent, immediately after resection of the tumour. Samples are digested and sorted using FACS as single cells  into lysis buffer. Cells are then stored until further processing for G&amp;T-seq. After sequencing, we will explore intra-tumour heterogeneity using computational approaches to integrate RNA and DNA data onto the tumour phylogeny\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The scope of the study is to investigate intra-tumor heterogeneity of sarcomas at the single-cell level. This will be achieved by sampling from different areas of a tumor and looking at the single level to the transcriptome and genome using G&amp;T-seq.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-21T12:15:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002867","title":"Somatic_mutation_and_clonal_evolution_in_the_pancreas_exome","description":"In this study, we aim to characterise the landscape of mutation and clonal selection in the pancreas. The data in this study will be generated by whole-exome sequencing of laser-dissected microbiopsies from the pancreas. The samples utilised in this study will include acini, ducts and islets from transplant donors.","abstract":"In this study, we aim to characterise the landscape of mutation and clonal selection in the pancreas. The data in this study will be generated by whole-exome sequencing of laser-dissected microbiopsies from the pancreas. The samples utilised in this study will include acini, ducts and islets from transplant donors.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002868","title":"UMI-Count Modeling and Differential Expression Analysis for Single Cell RNA Sequencing","description":"Read counting and unique molecular identifier (UMI) counting are the two principal gene expression quantification schemes used in single cell RNA sequencing (scRNA-seq) analysis. Using multiple scRNA-seq data sets, we reveal distinct distribution differences between the two schemes and conclude that the negative binomial model is a good approximation for UMI-counts, even in heterogeneous populations. We further propose a novel differential expression analysis algorithm based on negative binomial allowing independent dispersions in each group. Results show that it properly controls false positive rate (FDR) and achieves better power for UMI-counts than other recently developed packages for scRNA-seq analysis.","abstract":"Read counting and unique molecular identifier (UMI) counting are the two principal gene expression quantification schemes used in single cell RNA sequencing (scRNA-seq) analysis. Using multiple scRNA-seq data sets, we reveal distinct distribution differences between the two schemes and conclude that the negative binomial model is a good approximation for UMI-counts, even in heterogeneous populations. We further propose a novel differential expression analysis algorithm based on negative binomial allowing independent dispersions in each group. Results show that it properly controls false positive rate (FDR) and achieves better power for UMI-counts than other recently developed packages for scRNA-seq analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002869","title":"Exome and RNA sequencing data from 32 ocular and extraocular sebaceous carcinomas","description":"Sebaceous carcinomas (SeC) are cutaneous malignancies that, in rare cases, metastasize and prove fatal. Here we report whole exome sequencing on 32 SeC, revealing distinct mutational classes that explain both cancer ontogeny and clinical course. A UV-damage signature predominated 10/32 samples, while 9 were instead defined by microsatellite instability (MSI) mutations. UV-damage SeC exhibited poorly differentiated, infiltrative histopathologycompared to MSI signature SeC (p = 0.003), features previously associated with dissemination. Strikingly, UV-damage SeC transcriptomes and anatomic distributionclosely resembling those of cutaneous squamous cell carcinomas (SCC), implicating sun-exposed keratinocytes as a cell of origin. Like SCC, this UV-damage subclass harbors a high somatic mutation burden with &gt;50 mutations/Mb, predicting immunotherapeutic response. In contrast, ocular SeC acquire far fewer mutations without a dominant signature, but show frequent truncating mutations in the ZNF750 epidermal differentiation regulator. Our data exemplify how different mutational processes convergently drive histopathologically related but clinically distinct cancers.","abstract":"Sebaceous carcinomas (SeC) are cutaneous malignancies that, in rare cases, metastasize and prove fatal. Here we report whole exome sequencing on 32 SeC, revealing distinct mutational classes that explain both cancer ontogeny and clinical course. A UV-damage signature predominated 10/32 samples, while 9 were instead defined by microsatellite instability (MSI) mutations. UV-damage SeC exhibited poorly differentiated, infiltrative histopathologycompared to MSI signature SeC (p = 0.003), features previously associated with dissemination. Strikingly, UV-damage SeC transcriptomes and anatomic distributionclosely resembling those of cutaneous squamous cell carcinomas (SCC), implicating sun-exposed keratinocytes as a cell of origin. Like SCC, this UV-damage subclass harbors a high somatic mutation burden with &gt;50 mutations/Mb, predicting immunotherapeutic response. In contrast, ocular SeC acquire far fewer mutations without a dominant signature, but show frequent truncating mutations in the ZNF750 epidermal differentiation regulator. Our data exemplify how different mutational processes convergently drive histopathologically related but clinically distinct cancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-21T18:26:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002870","title":"Regulation of repetitive element expression in Acute Myeloid Leukemia.","description":"More than 50% of the human genome is made up of repetitive DNA sequences. These sequences were long considered non-functional. However, evidence is beginning to merge that many of these repetitive sequences contain regulatory elements. Furthermore, deregulation of repetitive elements can cause genomic instability and has been observed in solid cancers. We investigated repeat expression in Acute Myeloid Leukemia (AML) in collaboration with the laboratory of Michael Luebbert at the University Hospital Freiburg by total-RNA sequencing of a small number of primary patient samples. Our analysis has given insights into aberrant repeat transcription in AML and helps elucidate the role of these aberrant transcripts in non-solid tumor cells.","abstract":"More than 50% of the human genome is made up of repetitive DNA sequences. These sequences were long considered non-functional. However, evidence is beginning to merge that many of these repetitive sequences contain regulatory elements. Furthermore, deregulation of repetitive elements can cause genomic instability and has been observed in solid cancers. We investigated repeat expression in Acute Myeloid Leukemia (AML) in collaboration with the laboratory of Michael Luebbert at the University Hospital Freiburg by total-RNA sequencing of a small number of primary patient samples. Our analysis has given insights into aberrant repeat transcription in AML and helps elucidate the role of these aberrant transcripts in non-solid tumor cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002871","title":"Targeted exome sequencing of pleomorphic invasive lobular carcinoma (PILC).","description":"Pleomorphic invasive lobular carcinoma (PILC) is an aggressive variant of invasive lobular breast cancer that is associated with poor clinical outcomes.  Limited molecular data are available to explain the mechanistic basis for PILC behavior.  To address this issue, we performed targeted sequencing using the Beijing Genomics Institute (BGI) TumorCare™ gene panel that includes 1053 genes that were selected based upon their association with cancer.  This sequencing analysis identified genes that distinguish PILC from classic ILC (CILC) and invasive ductal carcinoma (IDC) by the incidence of their genomic changes.","abstract":"Pleomorphic invasive lobular carcinoma (PILC) is an aggressive variant of invasive lobular breast cancer that is associated with poor clinical outcomes.  Limited molecular data are available to explain the mechanistic basis for PILC behavior.  To address this issue, we performed targeted sequencing using the Beijing Genomics Institute (BGI) TumorCare™ gene panel that includes 1053 genes that were selected based upon their association with cancer.  This sequencing analysis identified genes that distinguish PILC from classic ILC (CILC) and invasive ductal carcinoma (IDC) by the incidence of their genomic changes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-22T18:48:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002872","title":"Whole genome analysis of mutation hotspots in gastric cancer","description":"Tissue-specific driver mutations in non-coding genomic regions remain undefined for most cancer types. In this study, we unbiasedly analysed 212 gastric cancer whole genomes to identify recurrently mutated non-coding regions in gastric cancer. Applying comprehensive statistical approa- ches to accurately model background mutational processes, we observe significant enrich- ment of non-coding indels (insertions/deletions) in three gastric lineage-specific genes. We further identify 34 mutation hotspots, of which 11 overlap CTCF binding sites (CBSs).","abstract":"Tissue-specific driver mutations in non-coding genomic regions remain undefined for most cancer types. In this study, we unbiasedly analysed 212 gastric cancer whole genomes to identify recurrently mutated non-coding regions in gastric cancer. Applying comprehensive statistical approa- ches to accurately model background mutational processes, we observe significant enrich- ment of non-coding indels (insertions/deletions) in three gastric lineage-specific genes. We further identify 34 mutation hotspots, of which 11 overlap CTCF binding sites (CBSs).","study_type":"Other","pubmed_ids":[29670109],"external_links":null,"is_released":true,"released_date":"2018-02-23T03:11:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002873","title":"Clonal_haematopoiesis_in_patients_with_AAA","description":"Recent advances in genomics have demonstrated that clonal haemopoiesis driven by leukaemia associated somatic mutations is a relatively common phenomenon that increases in frequency with advancing age. Whilst individuals with clonal haemopoiesis have an increased risk of developing haematological malignancies, they also have an increased mortality from other causes. Additionally, certain mutations are almost exclusively seen in individuals aged 70 years or older, whilst others are seen in individuals with non-haematological cancers including breast and ovarian. Recently, clonal haemopoiesis was found to be associated with a significantly increased risk of atherosclerotic cardiovascular disease. This association is thought to be causative with clonally-derived macrophages showing elevated expression of several chemokine and cytokine genes that contribute to atherosclerosis. \nAnother vascular pathology, abdominal aortic aneurysm (AAA), increases with age and shares risk factors with atherosclerosis (including smoking, male sex, high cholesterol). However, the impact of these risk factors and the overlap between AAA and atherosclerosis is poorly understood. To investigate a possible link between clonal haemopoiesis and AAA, we will study DNA samples from 300 patients with AAA and up to 200 controls for evidence of clonal haemopoiesis. This will be done using target DNA enrichment with biotinylated RNA baits followed by high throughput sequencing.","abstract":"Recent advances in genomics have demonstrated that clonal haemopoiesis driven by leukaemia associated somatic mutations is a relatively common phenomenon that increases in frequency with advancing age. Whilst individuals with clonal haemopoiesis have an increased risk of developing haematological malignancies, they also have an increased mortality from other causes. Additionally, certain mutations are almost exclusively seen in individuals aged 70 years or older, whilst others are seen in individuals with non-haematological cancers including breast and ovarian. Recently, clonal haemopoiesis was found to be associated with a significantly increased risk of atherosclerotic cardiovascular disease. This association is thought to be causative with clonally-derived macrophages showing elevated expression of several chemokine and cytokine genes that contribute to atherosclerosis. \nAnother vascular pathology, abdominal aortic aneurysm (AAA), increases with age and shares risk factors with atherosclerosis (including smoking, male sex, high cholesterol). However, the impact of these risk factors and the overlap between AAA and atherosclerosis is poorly understood. To investigate a possible link between clonal haemopoiesis and AAA, we will study DNA samples from 300 patients with AAA and up to 200 controls for evidence of clonal haemopoiesis. This will be done using target DNA enrichment with biotinylated RNA baits followed by high throughput sequencing.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-23T14:03:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002874","title":"Foundation Medicine Genomic Data Used to Identify Prognostic Markers and Fusion Genes in Multiple Myeloma","description":"The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma.  Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1, CDKN2C and TP53 where they have prognostic significance.\n\nIn addition, chromosomal rearrangements that result in oncogenic kinase activation are present in many solid and hematological malignancies, but none have been reported in multiple myeloma (MM). Here we detected fusion genes in 1.5% of patients.  These fusion genes were in-frame and the majority of them contained kinase domains from either receptor tyrosine kinases (ALK, ROS1, NTRK3, and FGFR1) or cytoplasmic kinases (BRAF, MAP3K14, and MAPK14) which would result in the activation of MEK/ERK, NF-κB or inflammatory signaling pathways. Fusion genes were present in smoldering MM, newly diagnosed MM and relapse patient samples indicating they are not solely late events. Most fusion genes were subclonal in nature, but one EML4-ALK fusion was clonal indicating it is a driver of disease pathogenesis. Samples with fusions of receptor tyrosine kinases were not found in conjunction with clonal Ras/Raf mutations indicating a parallel mechanism of MEK/ERK pathway activation. Fusion genes involving MAP3K14 (NIK), which regulates the NF-κB pathway, were detected as were t(14;17) rearrangements involving NIK in 2% of MM samples. Activation of kinases in myeloma through rearrangements presents an opportunity to use treatments existing in other cancers.","abstract":"The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma.  Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1, CDKN2C and TP53 where they have prognostic significance.\n\nIn addition, chromosomal rearrangements that result in oncogenic kinase activation are present in many solid and hematological malignancies, but none have been reported in multiple myeloma (MM). Here we detected fusion genes in 1.5% of patients.  These fusion genes were in-frame and the majority of them contained kinase domains from either receptor tyrosine kinases (ALK, ROS1, NTRK3, and FGFR1) or cytoplasmic kinases (BRAF, MAP3K14, and MAPK14) which would result in the activation of MEK/ERK, NF-κB or inflammatory signaling pathways. Fusion genes were present in smoldering MM, newly diagnosed MM and relapse patient samples indicating they are not solely late events. Most fusion genes were subclonal in nature, but one EML4-ALK fusion was clonal indicating it is a driver of disease pathogenesis. Samples with fusions of receptor tyrosine kinases were not found in conjunction with clonal Ras/Raf mutations indicating a parallel mechanism of MEK/ERK pathway activation. Fusion genes involving MAP3K14 (NIK), which regulates the NF-κB pathway, were detected as were t(14;17) rearrangements involving NIK in 2% of MM samples. Activation of kinases in myeloma through rearrangements presents an opportunity to use treatments existing in other cancers.","study_type":"Other","pubmed_ids":[28234347,29654269],"external_links":null,"is_released":true,"released_date":"2018-02-23T15:15:18+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002875","title":"This project aims to study human memory capacity, including short-term memory and long-term memory, systematically via genome-wide association studies","description":"Development of high-throughput genotyping platforms provides an opportunity to identify new genetic elements related to complex cognitive functions. Taking advantage of multi-level genomic analysis, here we studied the genetic basis of human short-term (STM, n=1,620) and long-term (LTM, n=1,526) memory functions. Heritability estimation based on single nucleotide polymorphism showed moderate heritability of short-term memory but very low heritability of long-term memory. In a two-step genome-wide association study, the markers rs13151012 and rs1558360 passed genome-wide significance (p &lt; 5×10-8) in digit-span STM task and for the first principal component shared by two STM tasks; however, none of them survived the replication. In turn, we selected the ten most significant single nucleotide polymorphisms (SNPs) for replication tests. Among them, a SNP near ZFAT was significantly associated with STM performance in another independent population of 2,789; a polymorphism within BCAT2 was significantly associated with LTM in another independent population of 1,865. Furthermore, we performed a pathway analysis based on the current genomic data and found six pathways significantly associated with STM capacity and one pathway associated with LTM capacity.","abstract":"Development of high-throughput genotyping platforms provides an opportunity to identify new genetic elements related to complex cognitive functions. Taking advantage of multi-level genomic analysis, here we studied the genetic basis of human short-term (STM, n=1,620) and long-term (LTM, n=1,526) memory functions. Heritability estimation based on single nucleotide polymorphism showed moderate heritability of short-term memory but very low heritability of long-term memory. In a two-step genome-wide association study, the markers rs13151012 and rs1558360 passed genome-wide significance (p &lt; 5×10-8) in digit-span STM task and for the first principal component shared by two STM tasks; however, none of them survived the replication. In turn, we selected the ten most significant single nucleotide polymorphisms (SNPs) for replication tests. Among them, a SNP near ZFAT was significantly associated with STM performance in another independent population of 2,789; a polymorphism within BCAT2 was significantly associated with LTM in another independent population of 1,865. Furthermore, we performed a pathway analysis based on the current genomic data and found six pathways significantly associated with STM capacity and one pathway associated with LTM capacity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-24T06:31:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002876","title":"Pan Prostate Cancer Group data","description":"The Pan Prostate Cancer Group intends to provide breakthrough advances from the analysis of a very large series of Whole Genome DNA data, contributed by many of the leading scientists and clinicians working in prostate cancer genomics generating Whole Genome DNA Sequence (WGS) data from prostate cancer patients. The accumulated data, collected and compared in a common format including common storage, re-analysis through a single pipeline, and investigation to achieve a variety of scientific goals, are presented in this series.\n \nThis project will provide a global framework for the future analysis of even larger series of genomes as costs of DNA sequencing, storage, and sequence analysis decrease.\n \nIn addition to these WGS data from different clinical categories, ethnicities, levels of aggressiveness, and disease managed by different treatments with information linked to long-term clinical follow up, we intend to add additional layers of data, including transcriptome and methylation data.\n \nThe current data series focuses primarily on the analysis of WGS data.\n \nFor further information, please refer to https://panprostate.org/, and The Pan Prostate Cancer Group Data Sharing Policy, EGAP00001003712.","abstract":"The Pan Prostate Cancer Group intends to provide breakthrough advances from the analysis of a very large series of Whole Genome DNA data, contributed by many of the leading scientists and clinicians working in prostate cancer genomics generating Whole Genome DNA Sequence (WGS) data from prostate cancer patients. The accumulated data, collected and compared in a common format including common storage, re-analysis through a single pipeline, and investigation to achieve a variety of scientific goals, are presented in this series.\n \nThis project will provide a global framework for the future analysis of even larger series of genomes as costs of DNA sequencing, storage, and sequence analysis decrease.\n \nIn addition to these WGS data from different clinical categories, ethnicities, levels of aggressiveness, and disease managed by different treatments with information linked to long-term clinical follow up, we intend to add additional layers of data, including transcriptome and methylation data.\n \nThe current data series focuses primarily on the analysis of WGS data.\n \nFor further information, please refer to https://panprostate.org/, and The Pan Prostate Cancer Group Data Sharing Policy, EGAP00001003712.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-27T10:21:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002877","title":"Transcriptional and DNA binding profiling of CEBPE in REH acute lymphoblastic leukaemia cells using shRNA RNA-Seq and ChIP-Seq","description":"ChIP-Seq - CEBPE - REH. The ETV6/RUNX1 translocated acute lymphoblastic leukaemia cell line REH was used to perform ChIP-Seq using a CEBPE antibody. Cells were fixed in 1% formaldehyde for 10mins, prior to preparation of chromatin using Active Motif Express ChIP-IT. 2ug of antibody (anti CEBPE Atlas Antibodies HPA002928)was added to 25ug of chromatin O/N at 4C with rotation. Duplicate reactions were pooled and purified. 10ng of ChIPd and input DNA used for Illumina NGS preparation (NEBNext ChIP-Seq Library kit; New England Biolabs), CEBPE and Input DNA ChIP samples were sequenced on a MiSeq using 150bp Kit v3 paired end and a HiSeq 2500 using 2x101 version 4 paired end (Illumina) respectively. Reactions performed in duplicate. shCEBPE RNA-Seq - REH. REH cells were lentivirally transduced with a pTRIPZ shRNA vector for transcriptional profiling of CEBPE. Two controls (empty and non-targeting) and two CEBPE shRNAs (V3THS_150517(A13), V3THS_404312(G3) Dharmacon, GE) were transduced into REH cells. Cells were treated with 1ug/ml doxycyclin for 144hrs and total RNA purified. Libraries were prepared using NEBNext Ultra II Directional RNA Library Prep Kit and sequenced on an Illuimna HiSeq 2500 using 2x101 version 4 paired end chemistry. 3 biological replicates of each samples were prepared.","abstract":"ChIP-Seq - CEBPE - REH. The ETV6/RUNX1 translocated acute lymphoblastic leukaemia cell line REH was used to perform ChIP-Seq using a CEBPE antibody. Cells were fixed in 1% formaldehyde for 10mins, prior to preparation of chromatin using Active Motif Express ChIP-IT. 2ug of antibody (anti CEBPE Atlas Antibodies HPA002928)was added to 25ug of chromatin O/N at 4C with rotation. Duplicate reactions were pooled and purified. 10ng of ChIPd and input DNA used for Illumina NGS preparation (NEBNext ChIP-Seq Library kit; New England Biolabs), CEBPE and Input DNA ChIP samples were sequenced on a MiSeq using 150bp Kit v3 paired end and a HiSeq 2500 using 2x101 version 4 paired end (Illumina) respectively. Reactions performed in duplicate. shCEBPE RNA-Seq - REH. REH cells were lentivirally transduced with a pTRIPZ shRNA vector for transcriptional profiling of CEBPE. Two controls (empty and non-targeting) and two CEBPE shRNAs (V3THS_150517(A13), V3THS_404312(G3) Dharmacon, GE) were transduced into REH cells. Cells were treated with 1ug/ml doxycyclin for 144hrs and total RNA purified. Libraries were prepared using NEBNext Ultra II Directional RNA Library Prep Kit and sequenced on an Illuimna HiSeq 2500 using 2x101 version 4 paired end chemistry. 3 biological replicates of each samples were prepared.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-27T11:47:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002878","title":"The_Genome_Diversity_in_Africa_project__building_a_HLA_data_resource_for_Africa","description":"Very little is known about the genetic diversity of the Human Leukocyte Antigen (HLA) region in African populations, and the availability of sequences from African individuals from this region are limited in existing HLA databases. Using single molecule real-time (SMRT) sequencing (PacBio)  and Illumina Myseq sequencing we aim to generate HLA genomic regional sequences for up to 3,700 individuals from representative populations across Africa.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Very little is known about the genetic diversity of the Human Leukocyte Antigen (HLA) region in African populations, and the availability of sequences from African individuals from this region are limited in existing HLA databases. Using single molecule real-time (SMRT) sequencing (PacBio)  and Illumina Myseq sequencing we aim to generate HLA genomic regional sequences for up to 3,700 individuals from representative populations across Africa.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002879","title":"RNA-seq of Liver Cancer","description":"The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer). The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors using whole genome (WGS) and whole exome sequencing (WGS), integrated with DNA methylation and RNA sequencing (RNA-seq) data. The present series corresponds to 161 RNA-seq samples from tumors with matched WES or WGS. Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem. It is the 3rd cause of cancer-related mortality. Advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. Thus, the development of next-generation sequencing technologies has made it possible to generate more comprehensive catalogues of somatic alteration events (single nucleotide substitutions, structural variations, and epigenetic changes) in liver cancer genome than ever before.","abstract":"The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer). The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors using whole genome (WGS) and whole exome sequencing (WGS), integrated with DNA methylation and RNA sequencing (RNA-seq) data. The present series corresponds to 161 RNA-seq samples from tumors with matched WES or WGS. Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem. It is the 3rd cause of cancer-related mortality. Advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. Thus, the development of next-generation sequencing technologies has made it possible to generate more comprehensive catalogues of somatic alteration events (single nucleotide substitutions, structural variations, and epigenetic changes) in liver cancer genome than ever before.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-02-28T12:21:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002880","title":"TArgeted therapy in Renal cell cancer: GEnetic and Tumour related biomarkers for response and toxicity","description":"The overall aim of EuroTARGET is to identify and characterize host and tumour related predictive biomarkers for response to targeted therapy in patients with (metastasized) renal cell cancer. Our overall concept is to focus on germline genome and tumour transcriptome, methylome and kinome-related biomarkers using an hypothesis-free and integrative approach and to evaluate promising findings via replication and functional assays. The main innovation of the EuroTARGET approach lies in the application and integration of cutting-edge high-throughput methodology and focused functional follow-up studies on relatively large numbers of RCC patient series treated with sorafenib or sunitinib or other targeted drug therapies.","abstract":"The overall aim of EuroTARGET is to identify and characterize host and tumour related predictive biomarkers for response to targeted therapy in patients with (metastasized) renal cell cancer. Our overall concept is to focus on germline genome and tumour transcriptome, methylome and kinome-related biomarkers using an hypothesis-free and integrative approach and to evaluate promising findings via replication and functional assays. The main innovation of the EuroTARGET approach lies in the application and integration of cutting-edge high-throughput methodology and focused functional follow-up studies on relatively large numbers of RCC patient series treated with sorafenib or sunitinib or other targeted drug therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002881","title":"Determining_mutation_burden_and_signatures_in_normal_tissues_of_patients_with_replication_repair_deficiency_syndromes","description":"Whole genome sequencing of normal tissues collected from various anatomical sites from patients with Constitutional Mismatch Repair Deficiency syndrome, Lynch syndrome and Polymerase Proofreading associated Polyposis.","abstract":"ndividuals with germline DNA repair deficiency syndromes experience continuous acquisition of somatic mutations which predisposes them to the development of specfic types of cancer. While DNA repair-deficient cancers have been well studied, the route from normal tissues towards cancer in these individuals remains uncharted.  This study is designed to determine the exposure of normal tissue genomes, collected from various anatomical sites, to the various mutational processes active in individuals suffering from replication repair deficient syndromes and improve our understanding how normal tissue develops into cancer in such a context.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002882","title":"scRNA-seq data of human nuclei collected from the temporal cortex of 17 individuals.","description":"Transcriptome analysis of single cells has tremendously increased our understanding of cellular heterogeneity in complex tissues. However, whole-cell transcriptomics cannot be applied to frozen tissue due to poor cell recovery after freezing. Human tissue is usually limited to tissue banks containing frozen material, and since single nuclei can be readily isolated from frozen tissues, human cell nuclei can substitute whole-cell analysis to extract single cell transcriptomes from human cells. Despite the importance of human tissue analysis, single-nucleus RNA-sequencing protocols are less developed than those for whole cells. SMARTSeq, either in form of custom-made SMARTSeq2 or as part of the Fluidigm C1 platform, provides a high resolution view of the transcriptome, has proven effective for whole-cell analysis and has recently been adapted to nuclei. Here, we show that the standard SMARTSeq2 protocol applied to single nuclei biases the amplification of single-nucleus transcriptomes due to unspecific capturing of transcripts, which can comprise the majority of reads in single-nucleus RNA-sequencing libraries. We demonstrate that modification of the SMARTSeq2 protocol with respect to template switching and cDNA amplification conditions generates sequencing libraries of higher complexity, allows for detection of more genes and reduces biases of the amplified transcriptome. In addition, modification of SMARTSeq2 chemistry allows for gene detection at shallower sequencing depth, thus increasing efficiency and decreasing cost.","abstract":"Transcriptome analysis of single cells has tremendously increased our understanding of cellular heterogeneity in complex tissues. However, whole-cell transcriptomics cannot be applied to frozen tissue due to poor cell recovery after freezing. Human tissue is usually limited to tissue banks containing frozen material, and since single nuclei can be readily isolated from frozen tissues, human cell nuclei can substitute whole-cell analysis to extract single cell transcriptomes from human cells. Despite the importance of human tissue analysis, single-nucleus RNA-sequencing protocols are less developed than those for whole cells. SMARTSeq, either in form of custom-made SMARTSeq2 or as part of the Fluidigm C1 platform, provides a high resolution view of the transcriptome, has proven effective for whole-cell analysis and has recently been adapted to nuclei. Here, we show that the standard SMARTSeq2 protocol applied to single nuclei biases the amplification of single-nucleus transcriptomes due to unspecific capturing of transcripts, which can comprise the majority of reads in single-nucleus RNA-sequencing libraries. We demonstrate that modification of the SMARTSeq2 protocol with respect to template switching and cDNA amplification conditions generates sequencing libraries of higher complexity, allows for detection of more genes and reduces biases of the amplified transcriptome. In addition, modification of SMARTSeq2 chemistry allows for gene detection at shallower sequencing depth, thus increasing efficiency and decreasing cost.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-01T09:56:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002883","title":"Luminist","description":"The study consists of ~ 1000 fresh frozen lung tumours. They will be sequenced using the Agilent baitset Quotation Number: GB-MH-1017-055. This is a collaboration set up by Dr. Ultan McDermott (former CASM) and Astra Zeneca.","abstract":"The study consists of ~ 1000 fresh frozen lung tumours. They will be sequenced using the Agilent baitset Quotation Number: GB-MH-1017-055. This is a collaboration set up by Dr. Ultan McDermott (former CASM) and Astra Zeneca.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002884","title":"Genomic analysis of Japanese gastric cancer (345 gastric cancers of NCC)","description":"As a contribution to the International Cancer Genome Consortium, whole exome sequencing of 345 Japanese gastric cancer (345 gastric cancers of NCC) with various histological subtypes have been conducted. This study aims to identify unique and common driver genes and molecular subtypes  in Japanese gastric cancer.","abstract":"As a contribution to the International Cancer Genome Consortium, whole exome sequencing of 345 Japanese gastric cancer (345 gastric cancers of NCC) with various histological subtypes have been conducted. This study aims to identify unique and common driver genes and molecular subtypes  in Japanese gastric cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-02T03:29:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002885","title":"Profiling_heterogeneity_in_Human_derived_IPSC_neurons","description":"The impact of genetic variants on molecular pathways that give rise to neurodegenerative diseases such as Alzheimer’s and Parkinson’s is best elucidated in the appropriate cell types and molecular contexts. Existing studies have focused on bulk profiling of mixed cell types, but have ignored assaying genetic effects across development and cell differentiation. At the core of this proposal is the idea to use single-cell assays to study genetic effects during differentiation of dopaminergic and cortical neurons to identify the sequence of molecular events from variants to healthy and diseased cell states in a cell-specific manner.\n\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"- Characterise intra-individual variation of cell types and single-cell states across cortical and dopaminergic differentiation. \n- Identify regulatory variants and gene targets that affect transcriptome level, cell-to-cell heterogeneity and the dynamics of cell differentiation.\n- Optionally: characterize the impact of engineered disease variants and mutant lines.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-02T09:38:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002886","title":"A whole genome analysis of single fetal human stem cells from the liver and the intestine","description":"Mutations of embryonic and fetal origin have the potential to affect a large proportion of adult cells and may alter cancer predisposition or lead to genetic disease syndromes. We have recently shown that human adult-stem cells progressively acquire approximately 40 novel tissue-specific mutations per year throughout postnatal life. Prenatal mutation rates are as yet unknown. Here we determined genome-wide mutation patterns of single stem cells in human development by sequencing of clonally expanded intestinal and liver organoid cultures of 2nd trimester human foetuses. Our results show that mutation rates in fetal stem cells are significantly higher than in adult stem cells.","abstract":"Mutations of embryonic and fetal origin have the potential to affect a large proportion of adult cells and may alter cancer predisposition or lead to genetic disease syndromes. We have recently shown that human adult-stem cells progressively acquire approximately 40 novel tissue-specific mutations per year throughout postnatal life. Prenatal mutation rates are as yet unknown. Here we determined genome-wide mutation patterns of single stem cells in human development by sequencing of clonally expanded intestinal and liver organoid cultures of 2nd trimester human foetuses. Our results show that mutation rates in fetal stem cells are significantly higher than in adult stem cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-02T09:46:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002887","title":"Circulating microRNAs disclose biology of normal cognitive function in healthy elderly people – a discovery twin study","description":"Circulating plasma miRNAs were assayed on a 754 miRNA OpenArray platform using 90 monozygotic elderly twins (73-95 years of age) and associated with mini mental state examination (MMSE) and a five component cognitive score (CCS) in an explorative study. Both ordinary individual and twin-pair analyses were performed with level of cognitive scores. A total of 278 miRNAs were expressed in plasma from at least ten participants. In this study we propose a shared biological path underlies dementia and normative cognitive aging.","abstract":"Circulating plasma miRNAs were assayed on a 754 miRNA OpenArray platform using 90 monozygotic elderly twins (73-95 years of age) and associated with mini mental state examination (MMSE) and a five component cognitive score (CCS) in an explorative study. Both ordinary individual and twin-pair analyses were performed with level of cognitive scores. A total of 278 miRNAs were expressed in plasma from at least ten participants. In this study we propose a shared biological path underlies dementia and normative cognitive aging.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002888","title":"Whole Genome Sequencing of HCC","description":"The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer). The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors using whole genome (WGS) and whole exome sequencing (WGS), integrated with DNA methylation and RNA sequencing (RNA-seq) data. The present series corresponds to 24 whole genome sequencing (12 Tumoral/Non-tumoral pairs). Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem. It is the 3rd cause of cancer-related mortality. Advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. Thus, the development of next-generation sequencing technologies has made it possible to generate more comprehensive catalogues of somatic alteration events (single nucleotide substitutions, structural variations, and epigenetic changes) in liver cancer genome than ever before.","abstract":"The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer). The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors using whole genome (WGS) and whole exome sequencing (WGS), integrated with DNA methylation and RNA sequencing (RNA-seq) data. The present series corresponds to 24 whole genome sequencing (12 Tumoral/Non-tumoral pairs). Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem. It is the 3rd cause of cancer-related mortality. Advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. Thus, the development of next-generation sequencing technologies has made it possible to generate more comprehensive catalogues of somatic alteration events (single nucleotide substitutions, structural variations, and epigenetic changes) in liver cancer genome than ever before.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-02T10:42:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002889","title":"Integrated genetic and epigenetic analysis of myxofibrosarcoma","description":"Myxofibrosarcoma (MFS) is a common histological subtype of adult soft tissue sarcoma characterized by an infiltrative growth pattern and a high propensity for local recurrence. We underwent whole exome sequencing, RNA sequencing, and methylation analysis of MFS.","abstract":"Myxofibrosarcoma (MFS) is a common histological subtype of adult soft tissue sarcoma characterized by an infiltrative growth pattern and a high propensity for local recurrence. We underwent whole exome sequencing, RNA sequencing, and methylation analysis of MFS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-02T11:29:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002890","title":"NeuroGenetics: mitochondrial, ataxias, spastic paraplegias and other rare neurogenetic conditions","description":"Inherited neurological diseases are clinically and genetically heterogeneous, and a molecular diagnosis is not possible in many patients. Having excluded common sporadic, inherited and metabolic causes, we used an unbiased whole exome sequencing approach in &gt;300 affected individuals, from randomly selected families. We defined the likely molecular diagnosis in approximately 60% of families. This revealed known and novel mutations in validated disease genes previously described in isolated families, which broadened the clinical phenotype of known disease genes. We have also reported several novel human disease genes.  The diagnostic yield was the same in both young and older-onset patients, including sporadic cases. We have demonstrated the impact of exome sequencing in a group of patients notoriously difficult to diagnose genetically. This has important implications for genetic counselling and diagnostic service provision.","abstract":"Inherited neurological diseases are clinically and genetically heterogeneous, and a molecular diagnosis is not possible in many patients. Having excluded common sporadic, inherited and metabolic causes, we used an unbiased whole exome sequencing approach in &gt;300 affected individuals, from randomly selected families. We defined the likely molecular diagnosis in approximately 60% of families. This revealed known and novel mutations in validated disease genes previously described in isolated families, which broadened the clinical phenotype of known disease genes. We have also reported several novel human disease genes.  The diagnostic yield was the same in both young and older-onset patients, including sporadic cases. We have demonstrated the impact of exome sequencing in a group of patients notoriously difficult to diagnose genetically. This has important implications for genetic counselling and diagnostic service provision.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002891","title":"Exome sequencing of 142 gastric cancer and matched normal from Japanese cohorts (UT)","description":"As a contribution to the International Cancer Genome Consortium, exome sequencing of 142 Japanese gastric cancer with various histological subtypes have been conducted. This study aims to identify unique and common driver genes and molecular subtypes  in Japanese gastric cancer. Please refer ICGC website for detail: http://icgc.org/icgc/cgp/69/420/1012357","abstract":"As a contribution to the International Cancer Genome Consortium, exome sequencing of 142 Japanese gastric cancer with various histological subtypes have been conducted. This study aims to identify unique and common driver genes and molecular subtypes  in Japanese gastric cancer. Please refer ICGC website for detail: http://icgc.org/icgc/cgp/69/420/1012357","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-02T15:37:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002892","title":"Exome sequencing of 102 gastric cancer and matched normal from Japanese cohorts (YCU)","description":"As a contribution to the International Cancer Genome Consortium, exome sequencing of 102 Japanese gastric cancer with various histological subtypes have been conducted. This study aims to identify unique and common driver genes and molecular subtypes  in Japanese gastric cancer. Please refer ICGC website for detail: http://icgc.org/icgc/cgp/69/420/1012357","abstract":"As a contribution to the International Cancer Genome Consortium, exome sequencing of 102 Japanese gastric cancer with various histological subtypes have been conducted. This study aims to identify unique and common driver genes and molecular subtypes  in Japanese gastric cancer. Please refer ICGC website for detail: http://icgc.org/icgc/cgp/69/420/1012357","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-02T15:40:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002893","title":"Exome sequencing demonstrates a dual origin of relapses in retinoic-acid resistant acute promyelocytic leukemia.","description":"Retinoic acid (RA) and arsenic target the PML/RARA driver of Acute Promyelocytic Leukemia (APL), their combination now curing over 95% patients. Here we report exome sequencing of 64 matched diagnosis/remission/relapses patients treated with historical RA/chemotherapy protocols. A first subgroup presents a high incidence of oncogenic mutations disrupting key epigenetic or transcriptional regulators (primarily WT1) or activating MAPK signaling at diagnosis. Relapses retain these cooperating oncogenes and exhibit additional oncogenic alterations and/or mutations impeding therapy response (RARA, NT5C2). The second group primarily exhibits FLT3 activation at diagnosis, which is lost upon relapse together with most other passenger mutations, implying that relapses derive from pre-leukemic PML/RARA-expressing cells that survived RA/chemotherapy. Accordingly, clonogenic activity of PML/RARA-immortalized progenitors ex vivo is only transiently affected by RA, but selectively abrogated by arsenic. Our studies stress the role of cooperating oncogenes in direct relapses and suggest that targeting pre-leukemic cells by arsenic contributes to its clinical efficacy.","abstract":"Retinoic acid (RA) and arsenic target the PML/RARA driver of Acute Promyelocytic Leukemia (APL), their combination now curing over 95% patients. Here we report exome sequencing of 64 matched diagnosis/remission/relapses patients treated with historical RA/chemotherapy protocols. A first subgroup presents a high incidence of oncogenic mutations disrupting key epigenetic or transcriptional regulators (primarily WT1) or activating MAPK signaling at diagnosis. Relapses retain these cooperating oncogenes and exhibit additional oncogenic alterations and/or mutations impeding therapy response (RARA, NT5C2). The second group primarily exhibits FLT3 activation at diagnosis, which is lost upon relapse together with most other passenger mutations, implying that relapses derive from pre-leukemic PML/RARA-expressing cells that survived RA/chemotherapy. Accordingly, clonogenic activity of PML/RARA-immortalized progenitors ex vivo is only transiently affected by RA, but selectively abrogated by arsenic. Our studies stress the role of cooperating oncogenes in direct relapses and suggest that targeting pre-leukemic cells by arsenic contributes to its clinical efficacy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-05T14:41:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002894","title":"The light chain IgLV3-21 defines a new poor prognostic subgroup in Chronic Lymphocytic Leukemia: results from a multicenter study","description":"Purpose: Unmutated (UM) immunoglobulin heavy chain region (IgHV) status or IgHV3-21 gene usage is associated with poor prognosis in chronic lymphocytic leukemia (CLL). Interestingly, IgHV3-21 is often co-expressed with light chain IgLV3-21 which is potentially able to trigger cell-autonomous BCR-mediated signaling. However this light chain has never been characterized independently of the heavy chain IgHV3-21.Experimental Design: we performed total RNA sequencing to characterize IgLV3-21 patients (n=32) and investigated IgLV3-21 prognostic impact in terms of treatment-free (TFS) and overall (OS) survival in 3 other independent cohorts for a total of 813 patients where IgLV3-21 presence was tested by real-time PCR and confirmed by Sanger sequencing.Results: Using total RNA sequencing to characterize 32 patients with high-risk CLL, we found a high frequency (28%) of IgLV3-21 rearrangements. Gene set enrichment analysis revealed that these patients present higher expression of genes responsible for ribosome biogenesis and translation initiation (P&lt;0.0001) and MYC target genes (P=0.0003). Patients with IgLV3-21 rearrangements displayed a significantly shorter TFS and OS (P&lt;0.05), in particular in IgHV mutated patients. In each of the 3 independent validation cohorts (n=813), we showed that IgLV3-21 rearrangements -similar to UM IgHV status- conferred poor prognosis compared to mutated IgHV (P&lt;0.0001). Importantly, we confirmed in multivariate analysis that this was independent of IgHV mutational status or subset #2 stereotyped receptor (P&lt;0.0001). Conclusions: We therefore demonstrate for the first time that a light chain can impact on CLL prognosis and that IgLV3-21 light chain usage defines a new poor prognostic subgroup in CLL.","abstract":"Purpose: Unmutated (UM) immunoglobulin heavy chain region (IgHV) status or IgHV3-21 gene usage is associated with poor prognosis in chronic lymphocytic leukemia (CLL). Interestingly, IgHV3-21 is often co-expressed with light chain IgLV3-21 which is potentially able to trigger cell-autonomous BCR-mediated signaling. However this light chain has never been characterized independently of the heavy chain IgHV3-21.Experimental Design: we performed total RNA sequencing to characterize IgLV3-21 patients (n=32) and investigated IgLV3-21 prognostic impact in terms of treatment-free (TFS) and overall (OS) survival in 3 other independent cohorts for a total of 813 patients where IgLV3-21 presence was tested by real-time PCR and confirmed by Sanger sequencing.Results: Using total RNA sequencing to characterize 32 patients with high-risk CLL, we found a high frequency (28%) of IgLV3-21 rearrangements. Gene set enrichment analysis revealed that these patients present higher expression of genes responsible for ribosome biogenesis and translation initiation (P&lt;0.0001) and MYC target genes (P=0.0003). Patients with IgLV3-21 rearrangements displayed a significantly shorter TFS and OS (P&lt;0.05), in particular in IgHV mutated patients. In each of the 3 independent validation cohorts (n=813), we showed that IgLV3-21 rearrangements -similar to UM IgHV status- conferred poor prognosis compared to mutated IgHV (P&lt;0.0001). Importantly, we confirmed in multivariate analysis that this was independent of IgHV mutational status or subset #2 stereotyped receptor (P&lt;0.0001). Conclusions: We therefore demonstrate for the first time that a light chain can impact on CLL prognosis and that IgLV3-21 light chain usage defines a new poor prognostic subgroup in CLL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-06T11:35:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002895","title":"Using human induced pluripotent stem cells (iPSC) and iPSC-derived neurons to explore cellular phenotypes associated with schizophrenia.","description":"Schizophrenia and major mental illness are common devastating conditions. Whilst partially effective treatments are available, none are disease-modifying. Notwithstanding important insights provided by animal models there is a need for novel models of mental illness to develop more effective therapies. A study of sporadic schizophrenia-derived human induced pluripotent stem cells (hiPS) has demonstrated a neuronal phenotype representing a powerful proof of concept of in vitro disease modeling, even for diseases with complex causation such as schizophrenia. These techniques have been used here to examine the behaviour of neural stem cells and neurons derived from fibroblasts from subjects carrying NDE1 copy number variations (CNVs) associated with increased risk of major mental illness. Using hiPS from individuals with and without disease-associated CNVs we have investigated how disease risk is conferred at a cellular and molecular level through detailed comparative studies of neural progenitor proliferation, neuronal morphology, physiology, cytoskeletal organization, synaptic function, glutamate (NMDA) receptor expression and also RNA sequencing and proteomic studies of these patient-derived cells.","abstract":"Schizophrenia and major mental illness are common devastating conditions. Whilst partially effective treatments are available, none are disease-modifying. Notwithstanding important insights provided by animal models there is a need for novel models of mental illness to develop more effective therapies. A study of sporadic schizophrenia-derived human induced pluripotent stem cells (hiPS) has demonstrated a neuronal phenotype representing a powerful proof of concept of in vitro disease modeling, even for diseases with complex causation such as schizophrenia. These techniques have been used here to examine the behaviour of neural stem cells and neurons derived from fibroblasts from subjects carrying NDE1 copy number variations (CNVs) associated with increased risk of major mental illness. Using hiPS from individuals with and without disease-associated CNVs we have investigated how disease risk is conferred at a cellular and molecular level through detailed comparative studies of neural progenitor proliferation, neuronal morphology, physiology, cytoskeletal organization, synaptic function, glutamate (NMDA) receptor expression and also RNA sequencing and proteomic studies of these patient-derived cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-06T14:21:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002896","title":"Somatic_mutation_profiling_of_intestinal_crypts_from_IBD","description":"In this project we want to investigate the role that somatic mutations in intestinal stem cells play in IBD. We will use laser capture microdissection to ascertain epithelial cells from an individual crypts/vilus. We will extract DNA from these and use a new low-input material library prep methods to make accurate libraries for sequencing. In this pilot phase of the project we will perform 15X whole-genome sequencing of a small number of crypts biopsied from four patients. Biopsies have been taken from inflammed and noninflammed patches to compare mutation rates and mutational signatures. We will also test if crypts from inflammed patches of a single patient are clonal (either within a given inflammed patch or across inflammed patches). We will quantify the rate of cancer driver mutations in inflammed and non-inflammed crypts.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"In this project we want to investigate the role that somatic mutations in intestinal stem cells play in IBD. We will use laser capture microdissection to ascertain epithelial cells from an individual crypts/vilus. We will extract DNA from these and use a new low-input material library prep methods to make accurate libraries for sequencing. In this pilot phase of the project we will perform 15X whole-genome sequencing of a small number of crypts biopsied from four patients. Biopsies have been taken from inflammed and noninflammed patches to compare mutation rates and mutational signatures. We will also test if crypts from inflammed patches of a single patient are clonal (either within a given inflammed patch or across inflammed patches). We will quantify the rate of cancer driver mutations in inflammed and non-inflammed crypts.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-07T12:49:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002897","title":"2015_AML_ETO","description":"This study includes 10 paired samples of 2015 Korean AML-ETO paitients.10 AML-ETO tumor samples are paired with each normal(Saliva or BM derived) sequencing data.The results of this WGS study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.","abstract":"This study includes 10 paired samples of 2015 Korean AML-ETO paitients.10 AML-ETO tumor samples are paired with each normal(Saliva or BM derived) sequencing data.The results of this WGS study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-08T01:48:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002898","title":"2015_AML_ETO_WGS_additional","description":"This study includes 2 paired samples of 2015 Korean AML-ETO paitients. 2 AML-ETO tumor samples are paired with each normal(Saliva or BM derived) sequencing data.The results of this WGS study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.","abstract":"This study includes 2 paired samples of 2015 Korean AML-ETO paitients. 2 AML-ETO tumor samples are paired with each normal(Saliva or BM derived) sequencing data.The results of this WGS study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-08T02:58:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002899","title":"Whole genome characterisation of lung cancer organoids and tissue","description":"Organoids are self-organizing 3D structures grown from stem cells that recapitulate essential aspects of organ structure and function. Here we describe a method to establish long-term expanding human airway organoids from broncho-alveolar biopsies or lavage material. The pseudostratified airway organoid epithelium consists of basal cells, functional multi-ciliated cells, mucus-producing goblet cells, and CC10-secreting club cells. Airway organoids derived from cystic fibrosis (CF) patients allow assessment of CFTR function in an organoid swelling assay. Organoid culture conditions also allow gene editing as well as the derivation of various types of lung cancer organoids. Respiratory syncytial virus (RSV) infection recapitulated central disease features and dramatically increases organoid cell motility, found to be driven by the non-structural viral NS2 protein. We conclude that human airway organoids represent versatile models for the in vitro study of hereditary, malignant, and infectious pulmonary disease.","abstract":"Organoids are self-organizing 3D structures grown from stem cells that recapitulate essential aspects of organ structure and function. Here we describe a method to establish long-term expanding human airway organoids from broncho-alveolar biopsies or lavage material. The pseudostratified airway organoid epithelium consists of basal cells, functional multi-ciliated cells, mucus-producing goblet cells, and CC10-secreting club cells. Airway organoids derived from cystic fibrosis (CF) patients allow assessment of CFTR function in an organoid swelling assay. Organoid culture conditions also allow gene editing as well as the derivation of various types of lung cancer organoids. Respiratory syncytial virus (RSV) infection recapitulated central disease features and dramatically increases organoid cell motility, found to be driven by the non-structural viral NS2 protein. We conclude that human airway organoids represent versatile models for the in vitro study of hereditary, malignant, and infectious pulmonary disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-08T08:41:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002900","title":"TCF11 study","description":"TCF11 ChIP-seq data on variant cell lines and the integrative study","abstract":"TCF11 ChIP-seq data on variant cell lines and the integrative study","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002901","title":"Hypothalamic transcriptome in Prader-Willi syndrome","description":"Transcriptional analysis of brain tissue from people with molecularly defined causes of obesity may highlight novel disease mechanisms and therapeutic targets. Prader-Willi syndrome (PWS) is a genetic obesity syndrome characterised by severe hyperphagia. We performed RNA sequencing of the hypothalamus from 4 individuals with PWS and 4 age-matched controls.","abstract":"Transcriptional analysis of brain tissue from people with molecularly defined causes of obesity may highlight novel disease mechanisms and therapeutic targets. Prader-Willi syndrome (PWS) is a genetic obesity syndrome characterised by severe hyperphagia. We performed RNA sequencing of the hypothalamus from 4 individuals with PWS and 4 age-matched controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-08T14:55:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002902","title":"Utilizing Whole exome sequencing to identify novel genetic variants in pediatric onset IBD","description":"Our research aims to evaluate genetic variants associated with specific clinical features in pediatric patients with Inflammatory Bowel Disease. Functional studies are carried out to confirm their pathological function. This study focuses on paediatric patients with inherited variants in Intestinal Alkaline phosphatase (ALPI).  The development of chronic intestinal inflammation is associated with several biological pathways making the treatment of early onset IBD patients very difficult. By improving our understanding of the genetic basis of individual patient phenotypes and correlating them with specific genes and pathways we hope to be better able to identify the best treatment options tailored to an individual's specific disease.","abstract":"Our research aims to evaluate genetic variants associated with specific clinical features in pediatric patients with Inflammatory Bowel Disease. Functional studies are carried out to confirm their pathological function. This study focuses on paediatric patients with inherited variants in Intestinal Alkaline phosphatase (ALPI).  The development of chronic intestinal inflammation is associated with several biological pathways making the treatment of early onset IBD patients very difficult. By improving our understanding of the genetic basis of individual patient phenotypes and correlating them with specific genes and pathways we hope to be better able to identify the best treatment options tailored to an individual's specific disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002903","title":"PATL2 is a key actor of oocyte maturation whose invalidation causes infertility in women and mice","description":"The genetic causes of oocyte meiotic deficiency (OMD), a form of primary infertility characterised by the production of immature oocytes, remain largely unexplored. Using whole exome sequencing, we found that 26% of a cohort of 23 subjects with OMD harboured the same homozygous nonsense pathogenic mutation in PATL2, a gene encoding a putative RNA-binding protein. Using Patl2 knockout mice, we confirmed that PATL2 deficiency disturbs oocyte maturation, since oocytes and zygotes exhibit morphological and developmental defects respectively. PATL2's amphibian orthologue is involved in the regulation of oocyte mRNA as a partner of CPEB. However, Patl2's expression profile throughout oocyte development in mice, alongside colocalisation experiments with Cpeb1, Msy2 and Ddx6 (three oocyte RNA-regulators) suggest an original role for Patl2 in Mammals. Accordingly, transcriptomic analysis of oocytes from WT and Patl2-/- animals demonstrated that in the absence of Patl2, expression levels of a select number of highly relevant genes involved in oocyte maturation and early embryonic development are deregulated. In conclusion, PATL2 is a novel actor of mammalian oocyte maturation whose invalidation causes OMD in humans.","abstract":"The genetic causes of oocyte meiotic deficiency (OMD), a form of primary infertility characterised by the production of immature oocytes, remain largely unexplored. Using whole exome sequencing, we found that 26% of a cohort of 23 subjects with OMD harboured the same homozygous nonsense pathogenic mutation in PATL2, a gene encoding a putative RNA-binding protein. Using Patl2 knockout mice, we confirmed that PATL2 deficiency disturbs oocyte maturation, since oocytes and zygotes exhibit morphological and developmental defects respectively. PATL2's amphibian orthologue is involved in the regulation of oocyte mRNA as a partner of CPEB. However, Patl2's expression profile throughout oocyte development in mice, alongside colocalisation experiments with Cpeb1, Msy2 and Ddx6 (three oocyte RNA-regulators) suggest an original role for Patl2 in Mammals. Accordingly, transcriptomic analysis of oocytes from WT and Patl2-/- animals demonstrated that in the absence of Patl2, expression levels of a select number of highly relevant genes involved in oocyte maturation and early embryonic development are deregulated. In conclusion, PATL2 is a novel actor of mammalian oocyte maturation whose invalidation causes OMD in humans.","study_type":"Other","pubmed_ids":[29661911],"external_links":null,"is_released":true,"released_date":"2018-03-09T14:46:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002904","title":"DNA Methylation and its Relation to Anti-citrullinated Protein Antibody Positivity and Rheumatoid Arthritis from a General Population-based Sample","description":"Objective: To compare DNA methylation in subjects positive vs. negative for anti-citrullinated protein antibodies (ACPA), a key serological marker of rheumatoid arthritis (RA) risk.Methods: Using banked serum from a random subset (N=3,600) of a large general population cohort (N=20,000), we identified subjects who were ACPA positive, and compared these to age and sex matched ACPA negative controls. We used a custom-designed methylome panel to conduct targeted bisulphite sequencing based investigation of 5M CpGs located in regulatory or hypomethylated regions of circulating blood cells. Using binomial regression model, we investigated the differentially methylated regions (DMRs) between ACPA positive versus negative subjects, and in an independent set of T-cells assayed in patients with RA.Results: We measured methylation in blood samples from 137 subjects, 63, 66 and 8 of which were ACPA positive, ACPA negative, and self-report RA, respectively. We identified 1,252 DMRs by considering dose-dependent effects where half (614) of them are underlined genetic effects. These DMRs are enriched in exon, intergenic CpG islands (CGI) and CGI shore regions as well as enhancer-like regions of several blood cell sub-types. Furthermore, the genes associated with these DMRs were enriched in pathways related to immune response such as osteoclast differentiation and MAPK signaling pathway. In addition, 42 (30%) of 142 RA-specific DMRs were well replicated in T-cells cohort.Conclusions: Our results highlight the advantages of sequencing-based high-resolution methylome mapping to reveal biological relevant DNA methylation changes in ACPA positive and negative subjects as well as RA patients.","abstract":"Objective: To compare DNA methylation in subjects positive vs. negative for anti-citrullinated protein antibodies (ACPA), a key serological marker of rheumatoid arthritis (RA) risk.Methods: Using banked serum from a random subset (N=3,600) of a large general population cohort (N=20,000), we identified subjects who were ACPA positive, and compared these to age and sex matched ACPA negative controls. We used a custom-designed methylome panel to conduct targeted bisulphite sequencing based investigation of 5M CpGs located in regulatory or hypomethylated regions of circulating blood cells. Using binomial regression model, we investigated the differentially methylated regions (DMRs) between ACPA positive versus negative subjects, and in an independent set of T-cells assayed in patients with RA.Results: We measured methylation in blood samples from 137 subjects, 63, 66 and 8 of which were ACPA positive, ACPA negative, and self-report RA, respectively. We identified 1,252 DMRs by considering dose-dependent effects where half (614) of them are underlined genetic effects. These DMRs are enriched in exon, intergenic CpG islands (CGI) and CGI shore regions as well as enhancer-like regions of several blood cell sub-types. Furthermore, the genes associated with these DMRs were enriched in pathways related to immune response such as osteoclast differentiation and MAPK signaling pathway. In addition, 42 (30%) of 142 RA-specific DMRs were well replicated in T-cells cohort.Conclusions: Our results highlight the advantages of sequencing-based high-resolution methylome mapping to reveal biological relevant DNA methylation changes in ACPA positive and negative subjects as well as RA patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002905","title":"Genomic Analysis of Wilms Tumor in Denys-Drash Syndrome-patients","description":"In this study we use whole exome sequencing and high resolution whole genome genotyping arrays to interrogate the genetic events that drive tumorigenesis of wilms tumor in patients with constitutional WT1-mutations (Denys-Drash Syndrome)","abstract":"In this study we use whole exome sequencing and high resolution whole genome genotyping arrays to interrogate the genetic events that drive tumorigenesis of wilms tumor in patients with constitutional WT1-mutations (Denys-Drash Syndrome)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002906","title":"Exome genotype data and phenotype data for the Oxford BioBank dataset.","description":"Phenotype rich Healthy Caucasian BioBank Cohort between the ages 30-50 with ethics to recall on genotype or phenotype.","abstract":"Phenotype rich Healthy Caucasian BioBank Cohort between the ages 30-50 with ethics to recall on genotype or phenotype.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002907","title":"HG_Retroduplications_in_Neurodevelopmental_Disorders","description":"Mobile genetic Elements (MEs) are pieces of DNA which, through an RNA intermediate, can generate new copies of themselves elsewhere in the host genome. Additionally, MEs can facilitate the duplication of non-ME transcripts, typically genes, through the mechanism of retroduplication. In humans, several disorders have been directly attributed to ME-derived mutagenesis but not to retroduplication events. We propose to whole genome sequence the 7 individuals with putative de novo gene retroduplications in order to identify the site of insertion.                                                  This sequencing will serve two primary purposes:                                                                                                                       1.) Identify the first documented case of a de novo retrogene insertion event causing a disease in humans              \n2.) provide additional whole genome sequencing of undiagnosed probands recruited into the DDD\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Mobile genetic Elements (MEs) are pieces of DNA which, through an RNA intermediate, can generate new copies of themselves elsewhere in the host genome. Additionally, MEs can facilitate the duplication of non-ME transcripts, typically genes, through the mechanism of retroduplication. In humans, several disorders have been directly attributed to ME-derived mutagenesis but not to retroduplication events. We propose to whole genome sequence the 7 individuals with putative de novo gene retroduplications in order to identify the site of insertion.                                                  This sequencing will serve two primary purposes:                                                                                                                       1.) Identify the first documented case of a de novo retrogene insertion event causing a disease in humans             \n2.) provide additional whole genome sequencing of undiagnosed probands recruited into the DDD","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-13T12:38:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002908","title":"Dynamics of multiple resistance mechanisms in plasma DNA and their clinical implications for NSCLC patients receiving EGFR-targeted therapies","description":"Background:The development of resistance mechanisms to targeted therapies is complicated by underlying tumour heterogeneity. When multiple resistance mechanisms co-exist, identifying the dominant driver(s) is critical for selection of treatment. Patients and methods:We studied the relative dynamics of multiple oncogenic drivers and resistance mechanisms in 50 patients with EGFR-mutant non-small cell lung cancer (NSCLC), during treatment with gefitinib and hydroxychloroquine (NCT00809237). We performed digital PCR and targeted deep sequencing of cell-free DNA from longitudinal plasma samples from all patients, and shallow whole genome sequencing of serial samples from three patients who underwent histological transformation to small-cell lung cancer (SCLC). ResultsEGFR activating mutations were assessed in tumour samples and accurately identified in plasma samples of 95% of patients (41/43). We identified additional mutations including EGFR T790M (31/50, 62%), TP53 (23/50, 46%), PIK3CA (7/50, 14%), and PTEN (4/50, 8%), and tracked their relative levels in plasma. Patients with both TP53 and EGFR mutations detected in plasma pre-treatment tended to have worse overall survival than those where only EGFR was detected. The resistance-conferring EGFR T790M mutation was identified in 62% of the patients who progressed. Changes in relative levels of T790M and activating mutations in EGFR corresponded to clinical responses in two patients who were given sequential treatments. Patients who progressed without T790M detected in plasma had worse PFS during TKI continuation, and developed alternative resistance mechanisms, that could be identified in plasma DNA, including SCLC-associated copy number changes and TP53 mutations, that tracked with progression and response to subsequent therapies. Conclusion:Longitudinal analysis of multiple oncogenic drivers in ctDNA may help identifying dominant mechanisms of resistance to EGFR-targeted therapies, and highlight the importance of monitoring genetic events that are not direct drug targets but provide non-invasive molecular information that may guide clinical management.","abstract":"Background:The development of resistance mechanisms to targeted therapies is complicated by underlying tumour heterogeneity. When multiple resistance mechanisms co-exist, identifying the dominant driver(s) is critical for selection of treatment. Patients and methods:We studied the relative dynamics of multiple oncogenic drivers and resistance mechanisms in 50 patients with EGFR-mutant non-small cell lung cancer (NSCLC), during treatment with gefitinib and hydroxychloroquine (NCT00809237). We performed digital PCR and targeted deep sequencing of cell-free DNA from longitudinal plasma samples from all patients, and shallow whole genome sequencing of serial samples from three patients who underwent histological transformation to small-cell lung cancer (SCLC). ResultsEGFR activating mutations were assessed in tumour samples and accurately identified in plasma samples of 95% of patients (41/43). We identified additional mutations including EGFR T790M (31/50, 62%), TP53 (23/50, 46%), PIK3CA (7/50, 14%), and PTEN (4/50, 8%), and tracked their relative levels in plasma. Patients with both TP53 and EGFR mutations detected in plasma pre-treatment tended to have worse overall survival than those where only EGFR was detected. The resistance-conferring EGFR T790M mutation was identified in 62% of the patients who progressed. Changes in relative levels of T790M and activating mutations in EGFR corresponded to clinical responses in two patients who were given sequential treatments. Patients who progressed without T790M detected in plasma had worse PFS during TKI continuation, and developed alternative resistance mechanisms, that could be identified in plasma DNA, including SCLC-associated copy number changes and TP53 mutations, that tracked with progression and response to subsequent therapies. Conclusion:Longitudinal analysis of multiple oncogenic drivers in ctDNA may help identifying dominant mechanisms of resistance to EGFR-targeted therapies, and highlight the importance of monitoring genetic events that are not direct drug targets but provide non-invasive molecular information that may guide clinical management.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-13T15:09:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002909","title":"Dsd","description":"dDDsdsD","abstract":"dDDsdsD","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002910","title":"Molecular analysis of giant cell lesions","description":"Giant cell lesions of the jaws are aggressive proliferative conditions that affect young and adult patients. The genetic profile of the tumour has not been established yet. In this project we performed whole exome sequencing of 18 samples and RNAseq (n=6) of giant cell lesions of the jaws. All the tumours are sporadic and only non-syndromic patients were included.","abstract":"Giant cell lesions of the jaws are aggressive proliferative conditions that affect young and adult patients. The genetic profile of the tumour has not been established yet. In this project we performed whole exome sequencing of 18 samples and RNAseq (n=6) of giant cell lesions of the jaws. All the tumours are sporadic and only non-syndromic patients were included.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-13T20:59:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002911","title":"Exploiting immune cell receptor information to quantify index switching in single cell transcriptome sequencing experiment","description":"By offering high sequencing speed and ultra-high-throughput at a low price, Illumina next-generation sequencing platforms has been widely adopted in recent years. However, an experiment with multiplexed library could be at risk of molecular recombination, known as “index switching”, which causes certain amount of reads to be assigned to an incorrect library. It is reported that a new advance, exclusion amplification (ExAmp) in conjunction with the patterned flow cell technology introduced on HiSeq 3000/HiSeq 4000/HiSeq X sequencing systems, potentially suffers from a higher rate of index switching than conventional bridge amplification.  We took advantage of the diverse but highly cell-unique expression of immune cell receptors to quantify index switching on single cell RNA-seq data that were sequenced on HiSeq 3500 and HiSeq 4000. By utilizing the unique T-cell receptor (TCR) expression, we could quantify the spread-of-signal from many different wells (n=51 from total three batches) due to index switching. We used TraCer to reconstruct full-length TCR from all samples, and then used Kallisto to quantify TCR gene expression. We found index switching in all three batches of experiments investigated. The median percentage of incorrectly detected markers was estimated to be 4.2% (interquartile range (IQR): 2.0%-8.7%). We did not detect any consistent pattern of certain indices to be more prone for switching than others, suggesting that index switching is a stochastic process. We confirm that index switching is a problem that affects all samples run in multiplexed libraries on Illumina HiSeq 3500 and HiSeq 4000 platforms.","abstract":"By offering high sequencing speed and ultra-high-throughput at a low price, Illumina next-generation sequencing platforms has been widely adopted in recent years. However, an experiment with multiplexed library could be at risk of molecular recombination, known as “index switching”, which causes certain amount of reads to be assigned to an incorrect library. It is reported that a new advance, exclusion amplification (ExAmp) in conjunction with the patterned flow cell technology introduced on HiSeq 3000/HiSeq 4000/HiSeq X sequencing systems, potentially suffers from a higher rate of index switching than conventional bridge amplification.  We took advantage of the diverse but highly cell-unique expression of immune cell receptors to quantify index switching on single cell RNA-seq data that were sequenced on HiSeq 3500 and HiSeq 4000. By utilizing the unique T-cell receptor (TCR) expression, we could quantify the spread-of-signal from many different wells (n=51 from total three batches) due to index switching. We used TraCer to reconstruct full-length TCR from all samples, and then used Kallisto to quantify TCR gene expression. We found index switching in all three batches of experiments investigated. The median percentage of incorrectly detected markers was estimated to be 4.2% (interquartile range (IQR): 2.0%-8.7%). We did not detect any consistent pattern of certain indices to be more prone for switching than others, suggesting that index switching is a stochastic process. We confirm that index switching is a problem that affects all samples run in multiplexed libraries on Illumina HiSeq 3500 and HiSeq 4000 platforms.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-14T10:20:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002912","title":"Single_cell_assessment_of_in_vivo_YFV_specific_CD8_T_cell_responses","description":"The aim of this study is to analyse the longtitudal dymanics of YFV-specific CD8 T cells following vaccination","abstract":"Vaccination against Yellow fever Virua(YFV) with the live-attenuated vaccine results in robust antibody as well as T cell responses that provide long life protection. This study will aalow us to recostract and assemble TCRs in combination with transcritpome information at the single level.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002913","title":"Liquid biopsies to track resistance in metastatic HER2 positive gastric cancer treated with anti-HER2 therapy","description":"Due to the limited response rate and rapidly emerged resistance, tracking the resistance to trastuzumab were critical for HER2+ advanced gastric cancer. Based on the promising consistence of targeted sequencing between tissue and plasma in 78 paired samples, we performed monitoring with time-course plasma samples of 24 HER2+ patients treated with trastuzumab. Higher HER2 copy number in progression than baseline and high frequent PIK3CA mutations were observed in most patients with innate resistance but not acquired resistance. ERBB2/4 was the most mutated gene accounting for trastuzumab resistance, and patients with PIK3CA/R1/C3 or ERBB2/4 mutations at baseline plasma have a significantly worse PFS. Besides, NF1 was found to contribute to trastuzumab resistance and further confirmed by in vitro and in vivo studies, while combined HER2 and MEK/ERK blockade may overcome the resistance. Our longitudinal ctDNA sequencing provides novel insights into gene alterations underlying resistance to trastuzumab in HER2+ gastric cancer.","abstract":"Due to the limited response rate and rapidly emerged resistance, tracking the resistance to trastuzumab were critical for HER2+ advanced gastric cancer. Based on the promising consistence of targeted sequencing between tissue and plasma in 78 paired samples, we performed monitoring with time-course plasma samples of 24 HER2+ patients treated with trastuzumab. Higher HER2 copy number in progression than baseline and high frequent PIK3CA mutations were observed in most patients with innate resistance but not acquired resistance. ERBB2/4 was the most mutated gene accounting for trastuzumab resistance, and patients with PIK3CA/R1/C3 or ERBB2/4 mutations at baseline plasma have a significantly worse PFS. Besides, NF1 was found to contribute to trastuzumab resistance and further confirmed by in vitro and in vivo studies, while combined HER2 and MEK/ERK blockade may overcome the resistance. Our longitudinal ctDNA sequencing provides novel insights into gene alterations underlying resistance to trastuzumab in HER2+ gastric cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002914","title":"Analysis of the reference epigenomes and regulatory landscape of CLL as a whole and its major clinico-biological subtypes (with mutated and unmutated IGHV) in the light of the normal B-cell differentiation.","description":"We have extensively characterized the reference epigenomes of seven primary chronic lymphocytic leukemia samples (CLLs) with mutated (n=5) and unmutated IGHV (n=2) as well as several mature B-cell subpopulations (naive B cells from blood and tonsil, germinal center B cells, memory B cells and plasma cells from tonsil) using genome-wide maps of six histone marks (H3K4me3, H3K4me1, H3K27ac, H3K36me3, H3K9me3 and H3K27me3), DNA accessibility (ATAC-seq), DNA methylation (whole-genome bisulfite sequencing) and gene expression (RNA-seq). Furthermore, we have mapped the regulatory chromatin landscape of 100 additional CLL cases using chIP-seq of H3K27ac and ATAC-seq and linked these data to additional layers of information (whole-genome and/or whole-exome sequencing (WGS/WES), RNA-seq and DNA methylation microarrays) studied in the context of the International Cancer Genome Consortium (ICGC).","abstract":"We have extensively characterized the reference epigenomes of seven primary chronic lymphocytic leukemia samples (CLLs) with mutated (n=5) and unmutated IGHV (n=2) as well as several mature B-cell subpopulations (naive B cells from blood and tonsil, germinal center B cells, memory B cells and plasma cells from tonsil) using genome-wide maps of six histone marks (H3K4me3, H3K4me1, H3K27ac, H3K36me3, H3K9me3 and H3K27me3), DNA accessibility (ATAC-seq), DNA methylation (whole-genome bisulfite sequencing) and gene expression (RNA-seq). Furthermore, we have mapped the regulatory chromatin landscape of 100 additional CLL cases using chIP-seq of H3K27ac and ATAC-seq and linked these data to additional layers of information (whole-genome and/or whole-exome sequencing (WGS/WES), RNA-seq and DNA methylation microarrays) studied in the context of the International Cancer Genome Consortium (ICGC).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002915","title":"Japan PBC-GWAS Haplotype Study","description":"Primary biliary cholangitis (PBC) susceptibility loci have largely been discovered through single SNP association testing. In this study, we report genic haplotype patterns associated with PBC risk genome-wide in two Japanese cohorts. Among the 74 genic PBC risk haplotype candidates we detected with a novel methodological approach in a discovery cohort of 1,937 Japanese, nearly two-thirds were replicated (49 haplotypes, Bonferroni-corrected P&lt;6.8x10-4) in an independent Japanese cohort (N=949). Along with corroborating known PBC-associated loci (TNFSF15, HLA-DRA), risk haplotypes may potentially model cis-interactions that regulate gene expression. For example, one replicated haplotype association (9q32-9q33.1, OR=1.7, P=3.0x10-21) consists of intergenic SNPs outside of the human leukocyte antigen (HLA) region that overlap regulatory histone mark peaks in liver and blood cells, and are significantly associated with TNFSF8 expression in whole blood. We also replicated a novel haplotype association involving non-HLA SNPs mapped to UMAD1 (7p21.3; OR=15.2, P=3.9x10-9) that overlap enhancer peaks in liver and memory Th cells. Our analysis demonstrates the utility of haplotype association analyses in discovering and characterizing PBC susceptibility loci.","abstract":"Primary biliary cholangitis (PBC) susceptibility loci have largely been discovered through single SNP association testing. In this study, we report genic haplotype patterns associated with PBC risk genome-wide in two Japanese cohorts. Among the 74 genic PBC risk haplotype candidates we detected with a novel methodological approach in a discovery cohort of 1,937 Japanese, nearly two-thirds were replicated (49 haplotypes, Bonferroni-corrected P&lt;6.8x10-4) in an independent Japanese cohort (N=949). Along with corroborating known PBC-associated loci (TNFSF15, HLA-DRA), risk haplotypes may potentially model cis-interactions that regulate gene expression. For example, one replicated haplotype association (9q32-9q33.1, OR=1.7, P=3.0x10-21) consists of intergenic SNPs outside of the human leukocyte antigen (HLA) region that overlap regulatory histone mark peaks in liver and blood cells, and are significantly associated with TNFSF8 expression in whole blood. We also replicated a novel haplotype association involving non-HLA SNPs mapped to UMAD1 (7p21.3; OR=15.2, P=3.9x10-9) that overlap enhancer peaks in liver and memory Th cells. Our analysis demonstrates the utility of haplotype association analyses in discovering and characterizing PBC susceptibility loci.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-14T17:05:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002916","title":"Copy_number_variation_in_mouse_oesophagus__Notch1","description":"We wish to determine how the mutational burden in mouse oesophagus changes in transgenic mice induced to carry mutations known to cover significant areas of human oesophagus.  Oesophaguses from mice carrying either mutations in P53, Notch1 or with altered immune systems  will be collected and DNA extracted from 2mm2 biopsies.   Low depth WGS will allow us to look at changes in copy number and structureal rearragements.  In some cases the mice will be further treated with DEN a carcinogen present in cigarette smoke.","abstract":"We wish to determine how the mutational burden in mouse oesophagus changes in transgenic mice induced to carry mutations known to cover significant areas of human oesophagus.  In some cases the mice will be further treated with DEN a carcinogen present in cigarette smoke.  Ultilising a combination of targetted high-depth sequencing and low depth WGS we will attempt to understand how the mutational landscape of the oesophagus changes with different background mutations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002917","title":"Human islet 3D chromatin maps provide insights into type 2 diabetes","description":"The transcriptional output of each cell type is controlled by thousands of enhancers, many of which contain genetic risk variants for common diseases such as type 2 diabetes (T2D). To gain insight into how enhancer variation influences diabetes risk, we created promoter capture Hi-C maps in human pancreatic islets. This linked diabetes-associated islet enhancers with their target genes, often located hundreds of kilobases away. We identified hubs that show spatial and functional connections between enhancersand target genes related to islet function and diabetes. We demonstrate that genetic variants distributed across hub enhancers have a major impact on T2D heritability, and use this knowledge to identify individuals in whom islet regulatory variation has a prominent role in T2D risk. Our results demonstrate the importance of 3D chromatin architecture for molecular interpretation of T2D genetic association signals, and define genomic spaces that harbor a distinct component of the T2D polygenic burden.","abstract":"The transcriptional output of each cell type is controlled by thousands of enhancers, many of which contain genetic risk variants for common diseases such as type 2 diabetes (T2D). To gain insight into how enhancer variation influences diabetes risk, we created promoter capture Hi-C maps in human pancreatic islets. This linked diabetes-associated islet enhancers with their target genes, often located hundreds of kilobases away. We identified hubs that show spatial and functional connections between enhancersand target genes related to islet function and diabetes. We demonstrate that genetic variants distributed across hub enhancers have a major impact on T2D heritability, and use this knowledge to identify individuals in whom islet regulatory variation has a prominent role in T2D risk. Our results demonstrate the importance of 3D chromatin architecture for molecular interpretation of T2D genetic association signals, and define genomic spaces that harbor a distinct component of the T2D polygenic burden.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-19T15:40:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002918","title":"Giselle Test - Prostate","description":"Testing Prostate Submission","abstract":"Testing Prostate Submission","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002919","title":"Genomic Heterogeneity and the Small Renal Mass","description":"Tumor heterogeneity is believed to represent a barrier to pre-operative genomic characterization in kidney cancer. Previous studies of heterogeneity in clear cell renal cell carcinoma (ccRCC) evaluated only large and metastatic tumors. In small renal tumors in which multiple biopsies are not feasible, the extent of heterogeneity remains unknown. In this study, we evaluated how the extent of genomic heterogeneity in small and large ccRCC. A total of 23 small (&lt;4cm ) and 24 large (&gt;7cm ) ccRCC had 3 regions sampled for evaluation of copy number, clear-cell A/clear-cell B (ccA/ccB) classification, and cell cycle progression (CCP) score. Small tumors have less genomic complexity and significantly fewer subclonal events. Pre-treatment genomic characterization based on a single biopsy in small ccRCC can provide insight into biologic potential to make clinical decisions.","abstract":"Tumor heterogeneity is believed to represent a barrier to pre-operative genomic characterization in kidney cancer. Previous studies of heterogeneity in clear cell renal cell carcinoma (ccRCC) evaluated only large and metastatic tumors. In small renal tumors in which multiple biopsies are not feasible, the extent of heterogeneity remains unknown. In this study, we evaluated how the extent of genomic heterogeneity in small and large ccRCC. A total of 23 small (&lt;4cm ) and 24 large (&gt;7cm ) ccRCC had 3 regions sampled for evaluation of copy number, clear-cell A/clear-cell B (ccA/ccB) classification, and cell cycle progression (CCP) score. Small tumors have less genomic complexity and significantly fewer subclonal events. Pre-treatment genomic characterization based on a single biopsy in small ccRCC can provide insight into biologic potential to make clinical decisions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-20T14:11:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002920","title":"SS18-SSX-mediated hijacking of BAF complexes drives synovial sarcoma","description":"Synovial sarcoma (SS) is defined by a recurrent t(x;18) chromosomal translocation, which produces the hallmark SS18-SSX oncogenic fusion. Incorporation of SS18-SSX into BAF complexes renders BAF complexes aberrant in two distinct manners: the addition of 78aa of SSX onto SS18, and concomitant loss of BAF47 assembly. However, the importance and functional contributions of each of these perturbations on BAF complex targeting and gene expression regulation remain unclear. Here we use an integrative set of genomic approaches in human cancer cell lines and primary tumor samples to define the mechanistic consequences of the SS18-SSX fusion oncoprotein. We find that SS18-SSX hijacks BAF complexes to broad polycomb domains to activate bivalent genes, driving a unique gene expression program distinct from other loss-of-function BAF complex malignancies. Importantly, restoration of BAF47 rescues enhancer activation but is dispensable for proliferative arrest in cell lines. These results demonstrate that gain-of-function SS18-SSX-mediated BAF complex targeting and gene activation is the driving event in SS, and present a mechanism by which distinct functions of BAF complexes can be co-opted to drive oncogenesis.","abstract":"Synovial sarcoma (SS) is defined by a recurrent t(x;18) chromosomal translocation, which produces the hallmark SS18-SSX oncogenic fusion. Incorporation of SS18-SSX into BAF complexes renders BAF complexes aberrant in two distinct manners: the addition of 78aa of SSX onto SS18, and concomitant loss of BAF47 assembly. However, the importance and functional contributions of each of these perturbations on BAF complex targeting and gene expression regulation remain unclear. Here we use an integrative set of genomic approaches in human cancer cell lines and primary tumor samples to define the mechanistic consequences of the SS18-SSX fusion oncoprotein. We find that SS18-SSX hijacks BAF complexes to broad polycomb domains to activate bivalent genes, driving a unique gene expression program distinct from other loss-of-function BAF complex malignancies. Importantly, restoration of BAF47 rescues enhancer activation but is dispensable for proliferative arrest in cell lines. These results demonstrate that gain-of-function SS18-SSX-mediated BAF complex targeting and gene activation is the driving event in SS, and present a mechanism by which distinct functions of BAF complexes can be co-opted to drive oncogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-20T16:18:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002921","title":"Genome Asia 100K Project","description":"The underrepresentation of non-European individuals in human genetic studies so far\nhas limited the diversity of individuals in genomic datasets and led to reduced medical\nrelevance for a large proportion of the world’s population. Population-specific\nreference genome datasets as well as genome-wide association studies in diverse\npopulations are needed to address this issue. Here we describe the pilot phase of the\nGenomeAsia 100K Project. This includes a whole-genome sequencing reference\ndataset from 1,739 individuals of 219 population groups and 64 countries across Asia.\nWe catalogue genetic variation, population structure, disease associations and\nfounder effects. We also explore the use of this dataset in imputation, to facilitate\ngenetic studies in populations across Asia and worldwide.","abstract":"The underrepresentation of non-European individuals in human genetic studies so far\nhas limited the diversity of individuals in genomic datasets and led to reduced medical\nrelevance for a large proportion of the world’s population. Population-specific\nreference genome datasets as well as genome-wide association studies in diverse\npopulations are needed to address this issue. Here we describe the pilot phase of the\nGenomeAsia 100K Project. This includes a whole-genome sequencing reference\ndataset from 1,739 individuals of 219 population groups and 64 countries across Asia.\nWe catalogue genetic variation, population structure, disease associations and\nfounder effects. We also explore the use of this dataset in imputation, to facilitate\ngenetic studies in populations across Asia and worldwide.","study_type":"Other","pubmed_ids":[31802016],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001002922","title":"Leeds Melanoma Cohort (LMC) gene expression study","description":"Array-based profiling (whole genome DASL HT12.4, Illumina Inc) in over 700 FFPE tumour blocks from the population-based Leeds Melanoma cohort recruited in the North of England, with a long follow up.\nData used in tumour immune micro-environment investigation (Nsengimana et al 2018, J Clin Invest  doi: 10.1172/JCI95351).","abstract":"Array-based profiling (whole genome DASL HT12.4, Illumina Inc) in over 700 FFPE tumour blocks from the population-based Leeds Melanoma cohort recruited in the North of England, with a long follow up.\nData used in tumour immune micro-environment investigation (Nsengimana et al 2018, J Clin Invest  doi: 10.1172/JCI95351).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-21T08:24:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002923","title":"Molecular evolution and clinical trajectories of prostate cancer identifies novel markers for risk stratification","description":"Prostate cancer is a highly heterogeneous disease that is thought to develop over many years. Identifying the earliest somatic changes can give important insights into the tumour evolution and aid in stratifying high- from low-risk diseases. Here we pursued integrative whole-genome, transcriptome and methylome-based analysis of early-onset prostate cancer patients. Characterisation of genomic alterations across 270 PCa tumours revealed age-related genomic alterations and mutation signatures including BRCAness and APOBEC. We used methylation- and expression-data to identify four molecular subgroups, which included a highly aggressive tumour subgroup that frequently involved recurrent duplications and increased expression of ESRP1. Analysis of 12,000 tissue-microarray tumour samples demonstrated that ESRP1 is a candidate biomarker associated with faster proliferation rate and shorter time to relapse. We combine the patterns of molecular co-occurrence, risk-stratification and subgroup information to deconvolute tumor heterogeneity, which reveal complex but recurrent clinical trajectories of prostate cancer.","abstract":"Prostate cancer is a highly heterogeneous disease that is thought to develop over many years. Identifying the earliest somatic changes can give important insights into the tumour evolution and aid in stratifying high- from low-risk diseases. Here we pursued integrative whole-genome, transcriptome and methylome-based analysis of early-onset prostate cancer patients. Characterisation of genomic alterations across 270 PCa tumours revealed age-related genomic alterations and mutation signatures including BRCAness and APOBEC. We used methylation- and expression-data to identify four molecular subgroups, which included a highly aggressive tumour subgroup that frequently involved recurrent duplications and increased expression of ESRP1. Analysis of 12,000 tissue-microarray tumour samples demonstrated that ESRP1 is a candidate biomarker associated with faster proliferation rate and shorter time to relapse. We combine the patterns of molecular co-occurrence, risk-stratification and subgroup information to deconvolute tumor heterogeneity, which reveal complex but recurrent clinical trajectories of prostate cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-22T08:19:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002924","title":"Using_RNAseq_to_investigate_the_links_between_genotype_and_the_underlying_genetic_mechanisms_of_disease_pathology_using_two_diverse_Salmonella_serotypes","description":"Salmonella enterica subsp. enterica can be divided into multiple serovars based on phenotypic (flagella, O-antigen, capsule) and biochemical properties, as well as now through genetic typing methods (MLST, WGS). Thousands of Salmonella have been sequenced via Illumina and other techniques. With a focus on the Salmonella Typhimurium and Salmonella Enteritidis strains that have been sequenced previously in our study, I2867, we now aim to utilize this data and investigate the links between genotype and the genetic mechanisms of host adaptation and disease pathology.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Salmonella enterica subsp. enterica can be divided into multiple serovars based on phenotypic (flagella, O-antigen, capsule) and biochemical properties, as well as now through genetic typing methods (MLST, WGS). Thousands of Salmonella have been sequenced via Illumina and other techniques. With a focus on the Salmonella Typhimurium and Salmonella Enteritidis strains that have been sequenced previously in our study, I2867, we now aim to utilize this data and investigate the links between genotype and the genetic mechanisms of host adaptation and disease pathology.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002925","title":"Data description of the study of Malaspinas et al. 2016 Nature","description":"Genomic and linguistic data allow for the characterization of the evolutionary history of human populations. To study the population history of Aboriginal Australians we collaborated with local Aboriginal Australian groups and collected saliva samples for genetic studies, as well as linguistic information. Specifically, we generated 83 Aboriginal Australian genomes from nine locations in Australia and recorded or inferred the language of each individual. We analysed this data in a previous publication. To allow other researchers to retrieve our data, we uploaded the genetic data at the managed access European Genome Phenome Archive (EGA) repository and the linguistic data at the unrestricted access chirila database. In the current manuscript, we first describe the collection of samples and associated permissions. We then detail the generation of a number of genomic datasets that were used for population genetics inference. We finally clarify the procedure that was outlined by the Griffith University Human Research Ethics Committee for researchers outside the original research team to apply for access to the genomic data and describe how to download the language data used for linguistic inference in our previous study.","abstract":"Genomic and linguistic data allow for the characterization of the evolutionary history of human populations. To study the population history of Aboriginal Australians we collaborated with local Aboriginal Australian groups and collected saliva samples for genetic studies, as well as linguistic information. Specifically, we generated 83 Aboriginal Australian genomes from nine locations in Australia and recorded or inferred the language of each individual. We analysed this data in a previous publication. To allow other researchers to retrieve our data, we uploaded the genetic data at the managed access European Genome Phenome Archive (EGA) repository and the linguistic data at the unrestricted access chirila database. In the current manuscript, we first describe the collection of samples and associated permissions. We then detail the generation of a number of genomic datasets that were used for population genetics inference. We finally clarify the procedure that was outlined by the Griffith University Human Research Ethics Committee for researchers outside the original research team to apply for access to the genomic data and describe how to download the language data used for linguistic inference in our previous study.","study_type":"Other","pubmed_ids":[27654914],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002926","title":"502 present-day genotypes included in the '137 ancient human genomes from across the Eurasian steppe' publication","description":"For thousands of years, the Eurasian steppe has been a centre for human migrations and cultural changes. To understand its population history following the Bronze Age migrations, 137 ancient humans were sequenced. These ancient DNA sequences were notably compared to the genetic data of present-day populations from Eurasia. Besides already published data, 502 individuals currently living in Inner Asia and Jordania were sampled and newly genotyped on diverse DNA-arrays. These new data, merged as a single dataset of 242,406 autosomal SNPs, are included in the present ENA study.","abstract":"For thousands of years, the Eurasian steppe has been a centre for human migrations and cultural changes. To understand its population history following the Bronze Age migrations, 137 ancient humans were sequenced. These ancient DNA sequences were notably compared to the genetic data of present-day populations from Eurasia. Besides already published data, 502 individuals currently living in Inner Asia and Jordania were sampled and newly genotyped on diverse DNA-arrays. These new data, merged as a single dataset of 242,406 autosomal SNPs, are included in the present ENA study.","study_type":"Other","pubmed_ids":[29743675],"external_links":null,"is_released":true,"released_date":"2018-03-23T14:33:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002927","title":"RNA-seq analysis of human skin","description":"RNA sequencing analysis comparing epidermal subpopulations in normal and inflamed skin.","abstract":"RNA sequencing analysis comparing epidermal subpopulations in normal and inflamed skin.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-23T21:50:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002928","title":"Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma","description":"We examined pre-treatment tumors from participants of the IMmotion150 trial. Biomarker analyses indicate that high angiogenesis gene expression was associated with improved PFS within the sunitinib arm, and high T-effector/IFNγ response (Teff) gene expression with longer PFS in atezolizumab + bevacizumab vs sunitinib patients. In high Teff tumors, concomitant high myeloid inflammation was associated with worse PFS in the atezolizumab monotherapy arm; adding bevacizumab to atezolizumab in this subgroup improved PFS vs atezolizumab. Molecular profiles suggest that prediction of outcomes with VEGF inhibitors and immunotherapy may be possible in mRCC, and bevacizumab may overcome myeloid inflammation-associated atezolizumab resistance.","abstract":"We examined pre-treatment tumors from participants of the IMmotion150 trial. Biomarker analyses indicate that high angiogenesis gene expression was associated with improved PFS within the sunitinib arm, and high T-effector/IFNγ response (Teff) gene expression with longer PFS in atezolizumab + bevacizumab vs sunitinib patients. In high Teff tumors, concomitant high myeloid inflammation was associated with worse PFS in the atezolizumab monotherapy arm; adding bevacizumab to atezolizumab in this subgroup improved PFS vs atezolizumab. Molecular profiles suggest that prediction of outcomes with VEGF inhibitors and immunotherapy may be possible in mRCC, and bevacizumab may overcome myeloid inflammation-associated atezolizumab resistance.","study_type":"Other","pubmed_ids":[29867230],"external_links":null,"is_released":true,"released_date":"2018-03-23T23:57:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001002929","title":"Human_Developmental_Cell_Atlas_HDCA___WGS","description":"Single cell + bulk genomics study for immune and hematopoietic organs during human fetal development","abstract":"Whole genome sequencing of tissues for single-cell genotyping as part of the Human Developmental Cell Atlas (HDCA)","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-26T10:53:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002930","title":"Human_Developmental_Cell_Atlas_HDCA___RNA","description":"Single cell + bulk genomics study for immune and hematopoietic organs during human fetal development","abstract":"Tissue bulk RNAseq genome sequencing for the Human Developmental Cell Atlas (HDCA)","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002931","title":"Benchmarking_CRISPR_Whole_genome_Drop_out_Screen___B_S","description":"This study is a benchmarking exercise to explore potential source of variation between different CRISPR drop out libraries.","abstract":"Whole genome CRISPR drop-out screens have developed as a key tool in molecular biology. Various methods of screening exist in different institutes e.g. sgRNA design. This project aims to explore potential sources of variations and their effect on data generated. In order to achieve this, we have worked with our colleagues in the Broad Institute Boston where we have exchanged cell lines &amp; CRISPR reagents to perform screens at both sites and compare data generated.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-26T13:37:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002932","title":"RNAseq of 76 samples from Uveal Melanoma tumors","description":"Hotspot mutations in the spliceosome gene SF3B1 are reported in 20% of uveal melanomas. SF3B1 is involved in 3'-splice site (3'ss) recognition during RNA splicing; however, the molecular mechanisms of its mutation have remained unclear. Here we show, using RNA-Seq analyses of uveal melanoma, that the SF3B1 R625/K666 mutation results in deregulated splicing at a subset of junctions, mostly by the use of alternative 3'ss","abstract":"Hotspot mutations in the spliceosome gene SF3B1 are reported in 20% of uveal melanomas. SF3B1 is involved in 3'-splice site (3'ss) recognition during RNA splicing; however, the molecular mechanisms of its mutation have remained unclear. Here we show, using RNA-Seq analyses of uveal melanoma, that the SF3B1 R625/K666 mutation results in deregulated splicing at a subset of junctions, mostly by the use of alternative 3'ss","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-26T16:00:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002933","title":"Single-cell transcriptome sequencing of regulatory and conventional T cells in breast cancer patients and healthy individuals.","description":"Identification of tumor-specific effects on gene expression profile of regulatory T cells and conventional T cells in humans, investigation of the clonal origin of regulatory T cells and impact analysis of tumor-specific conversion of conventional T cells into induced regulatory T cells on the peripheral regulatory T cell repertoire in humans.","abstract":"Identification of tumor-specific effects on gene expression profile of regulatory T cells and conventional T cells in humans, investigation of the clonal origin of regulatory T cells and impact analysis of tumor-specific conversion of conventional T cells into induced regulatory T cells on the peripheral regulatory T cell repertoire in humans.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-27T09:59:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002934","title":"HG_Transcriptome_sequencing_in_the_INTERVAL_cohort_pilot_","description":"We performed bulk RNA-sequencing on peripheral blood collected from 4,732\nblood donors recruited as part of the INTERVAL study. Using these data, we\nmapped gene expression and splicing quantitative trait loci (QTLs). Then,\nwe integrated these data with protein, metabolite and lipid QTLs in the\nsame individuals. The study aimed to identify the shared genetic etiology\nacross transcriptional phenotypes, molecular traits and health outcomes in\nhumans.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We performed bulk RNA-sequencing on peripheral blood collected from 4,732\nblood donors recruited as part of the INTERVAL study. Using these data, we\nmapped gene expression and splicing quantitative trait loci (QTLs). Then,\nwe integrated these data with protein, metabolite and lipid QTLs in the\nsame individuals. The study aimed to identify the shared genetic etiology\nacross transcriptional phenotypes, molecular traits and health outcomes in\nhumans.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002935","title":"Infant_Spindle_Tumour_Study","description":"We aim to describe the transcriptomic landscape of infant spindle cell tumours.","abstract":"We aim to describe the transcriptomic landscape of infant spindle cell tumours.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-27T15:18:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002936","title":"Genome-wide discovery of somatic coding and regulatory variants in Diffuse Large B-cell Lymphoma","description":"Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer originating from mature B-cells.  Prognosis is strongly associated with molecular subgroup, although the driver mutations that distinguish the two main subgroups remain poorly defined. Through an integrative analysis of whole genomes, exomes, and transcriptomes, we have uncovered genes and non-coding loci that are commonly mutated in DLBCL. Our analysis has identified novel cis-regulatory sites, and implicates recurrent mutations in the 3'UTR of NFKBIZ as a novel mechanism of oncogene deregulation and NFκB pathway activation in the activated B-cell (ABC) subgroup. Small amplifications associated with over-expression of FCGR2B (the Fcγ receptor  protein  IIB),  primarily  in  the  germinal  centre  B-cell  (GCB)  subgroup,  correlate with poor patient outcomes suggestive of a novel oncogene.  These results expand the list of subgroup driver mutations that may facilitate implementation of improved diagnostic assays and could offer new avenues for the development of targeted therapeutics.","abstract":"Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer originating from mature B-cells.  Prognosis is strongly associated with molecular subgroup, although the driver mutations that distinguish the two main subgroups remain poorly defined. Through an integrative analysis of whole genomes, exomes, and transcriptomes, we have uncovered genes and non-coding loci that are commonly mutated in DLBCL. Our analysis has identified novel cis-regulatory sites, and implicates recurrent mutations in the 3'UTR of NFKBIZ as a novel mechanism of oncogene deregulation and NFκB pathway activation in the activated B-cell (ABC) subgroup. Small amplifications associated with over-expression of FCGR2B (the Fcγ receptor  protein  IIB),  primarily  in  the  germinal  centre  B-cell  (GCB)  subgroup,  correlate with poor patient outcomes suggestive of a novel oncogene.  These results expand the list of subgroup driver mutations that may facilitate implementation of improved diagnostic assays and could offer new avenues for the development of targeted therapeutics.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-27T19:09:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002937","title":"GoDARTS T2D-GENES Exome Sequencing Study is a subset of the ~52,000 Type 2 diabetes exome sequencing project.","description":"The GoDARTS T2D-GENES Exome sequencing study is a subset of a larger Type 2 Diabetes Exome Sequencing project. This effort is a collaboration of six consortia with various funding mechanisms that have joined together to investigate genetic variants for type 2 diabetes (T2D) using the largest T2D case/control sample set compiled to date and includes samples from: T2D-GENES, GoT2D, ESP, SIGMA T2D, LuCAMP, and ProDIGY. \n\nThis data generated from the Genetics of Diabetes and Audit Research Tayside Study (GoDARTS) cohort was part of the T2D-GENES (Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples) consortium, which is a NIDDK-funded international research consortium that seeks to identify genetic variants for T2D through multiethnic sequencing studies. Sequencing for the GoDARTS study was performed at the Broad Institute using Illumina Rapid Capture on Illumina HiSeq machines.","abstract":"The GoDARTS T2D-GENES Exome sequencing study is a subset of a larger Type 2 Diabetes Exome Sequencing project. This effort is a collaboration of six consortia with various funding mechanisms that have joined together to investigate genetic variants for type 2 diabetes (T2D) using the largest T2D case/control sample set compiled to date and includes samples from: T2D-GENES, GoT2D, ESP, SIGMA T2D, LuCAMP, and ProDIGY. \n\nThis data generated from the Genetics of Diabetes and Audit Research Tayside Study (GoDARTS) cohort was part of the T2D-GENES (Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples) consortium, which is a NIDDK-funded international research consortium that seeks to identify genetic variants for T2D through multiethnic sequencing studies. Sequencing for the GoDARTS study was performed at the Broad Institute using Illumina Rapid Capture on Illumina HiSeq machines.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-27T21:58:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002938","title":"Gastric_Mutational_Signatures__GMS_","description":"This study aims to characterise the mutation burdens and signatures of adult stem cells derived from different regions of the stomach in order to gain insight into the causes and preclinical evolution of the diverse cancer subtypes. Clonal populations of cells from different anatomical locations of the stomach will be derived through organoid culture and/or laser microdissection and interrogated by whole genome sequencing and/or targeted pulldown. A total of circa 300 samples from 20 – 30 donors (cancer and non-cancer patients undergoing total/partial gastrectomy) will be analysed for mutational burden and signatures and genomic findings correlated with topology, age, risk factors and different stages of pre-neoplastic or neoplastic progression.","abstract":"Gastric cancer is common worldwide, but has especially high incidence and mortality locally in Hong Kong and China. Cancer, an age-related disease, is caused by mutations that progressively accumulate during the life-time of an individual in the long-living adult stem cells residing in each organ that are responsible for fuelling cell renewal and repair.  The opposing biological forces of processes that generate mutations (which include exogenous and endogenous mutagens inflicting DNA damage, DNA editing and errors of DNA replication) and processes of DNA repair (that protect normal cells against them) act in concert to shape the final outcomes of mutation burden in cells and cancer risk. These mutational and repair processes leave a footprint in DNA, known as a “mutational signature”, which enables assessment of their past activity. With recent advances in next-generation sequencing technologies and the ability to isolate clonal units, it is now possible to effectively and completely decipher all the somatic mutations acquired during the life-time of an individual adult stem cell. These provide crucial information on mutational loads and signatures that in turn reflect the causes and origins of the cancer, with implications for cancer risk prediction, early detection and intervention. Using whole-genome and deep targeted sequencing, we aim to study the mutational load and signatures of adult stem cells, from healthy and from cancer patients of different ages, and residing in different regions of the stomach. We plan to study their relationship with age, topology, risk factors, pre-neoplastic changes of gastritis, intestinal metaplasia and dysplasia, as well as comparing them to the mutational burdens and signatures found in cancer cells from the same individuals. This study will lead to the identification of differential mutational burdens and mutational signatures specific for each topological region of the stomach and their link to previously known or new carcinogenic agents or processes; as well as their consequential contribution to stepwise pre-neoplastic to neoplastic progression in different subtypes of gastric cancer. The results will generate insight into the differences in mutational burden and signatures that reflect the potential of various carcinogenic agents to affect different regions of the stomach, may provide an explanation for the site-specific predilection for different subtypes of gastric cancer, and inform strategies for comprehensive cancer prevention, early detection and intervention that will encompass all the diverse gastric cancer subtypes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-28T10:30:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002939","title":"Gastric_Mutational_Signatures__GMS_","description":"This study aims to characterise the mutation burdens and signatures of adult stem cells derived from different regions of the stomach in order to gain insight into the causes and preclinical evolution of the diverse cancer subtypes. Clonal populations of cells from different anatomical locations of the stomach will be derived through organoid culture and/or laser microdissection and interrogated by whole genome sequencing and/or targeted pulldown. A total of circa 300 samples from 20 – 30 donors (cancer and non-cancer patients undergoing total/partial gastrectomy) will be analysed for mutational burden and signatures and genomic findings correlated with topology, age, risk factors and different stages of pre-neoplastic or neoplastic progression.","abstract":"Gastric cancer is common worldwide, but has especially high incidence and mortality locally in Hong Kong and China. Cancer, an age-related disease, is caused by mutations that progressively accumulate during the life-time of an individual in the long-living adult stem cells residing in each organ that are responsible for fuelling cell renewal and repair.  The opposing biological forces of processes that generate mutations (which include exogenous and endogenous mutagens inflicting DNA damage, DNA editing and errors of DNA replication) and processes of DNA repair (that protect normal cells against them) act in concert to shape the final outcomes of mutation burden in cells and cancer risk. These mutational and repair processes leave a footprint in DNA, known as a “mutational signature”, which enables assessment of their past activity. With recent advances in next-generation sequencing technologies and the ability to isolate clonal units, it is now possible to effectively and completely decipher all the somatic mutations acquired during the life-time of an individual adult stem cell. These provide crucial information on mutational loads and signatures that in turn reflect the causes and origins of the cancer, with implications for cancer risk prediction, early detection and intervention. Using whole-genome and deep targeted sequencing, we aim to study the mutational load and signatures of adult stem cells, from healthy and from cancer patients of different ages, and residing in different regions of the stomach. We plan to study their relationship with age, topology, risk factors, pre-neoplastic changes of gastritis, intestinal metaplasia and dysplasia, as well as comparing them to the mutational burdens and signatures found in cancer cells from the same individuals. This study will lead to the identification of differential mutational burdens and mutational signatures specific for each topological region of the stomach and their link to previously known or new carcinogenic agents or processes; as well as their consequential contribution to stepwise pre-neoplastic to neoplastic progression in different subtypes of gastric cancer. The results will generate insight into the differences in mutational burden and signatures that reflect the potential of various carcinogenic agents to affect different regions of the stomach, may provide an explanation for the site-specific predilection for different subtypes of gastric cancer, and inform strategies for comprehensive cancer prevention, early detection and intervention that will encompass all the diverse gastric cancer subtypes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-28T10:35:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002940","title":"Germline DNMT3A mutation in mother-son pair with AML","description":"A mother/son pair with adult onset diploid AML were evaluated and found to have a dominant negative germline mutation in DNMT3A that is associated with global hypomethylation","abstract":"A mother/son pair with adult onset diploid AML were evaluated and found to have a dominant negative germline mutation in DNMT3A that is associated with global hypomethylation","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-03-30T05:32:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002941","title":"The genomic landscape of lung adenocarcinoma in East Asians","description":"We performed exome sequencing of 210 and transcriptome sequencing of 181 LUADs of Chinese patients. For more details, please see publication \"Genomic landscape of lung adenocarcinoma in East Asians\" by Chen J. et. al. in Nature Genetics 2020. https://www.nature.com/articles/s41588-019-0569-6.","abstract":"We performed exome sequencing of 210 and transcriptome sequencing of 181 LUADs of Chinese patients. For more details, please see publication \"Genomic landscape of lung adenocarcinoma in East Asians\" by Chen J. et. al. in Nature Genetics 2020. https://www.nature.com/articles/s41588-019-0569-6.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-03T06:09:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002942","title":"Hypoxic volume and hypoxia-associated gene expression in oropharyngeal squamous cell carcinoma","description":"Hypoxia imaging is a promising tool for targeted therapy in head and neck cancers but the links between imaging features and underlying molecular characteristics of the tumour have not been investigated. The aim of this study was to compare hypoxia biomarkers and gene expression in oropharyngeal squamous cell carcinoma (OPSCC) diagnostic biopsies with hypoxia imaged with 64Cu-ATSM PET/CT. 64Cu-ATSM imaging, molecular and clinical data were obtained for 15 patients. Primary tumour SUVmax, tumour to muscle ratio (TMR) and hypoxic volume were tested for association with reported hypoxia gene signatures in diagnostic biopsies. A putative gene signature for hypoxia in OPSCCs (hypoxic volume-associated gene signature (HVS)) was derived. [Suh et al. Brit J Cancer (2017) doi: 10.1038/bjc.2017.66]","abstract":"Hypoxia imaging is a promising tool for targeted therapy in head and neck cancers but the links between imaging features and underlying molecular characteristics of the tumour have not been investigated. The aim of this study was to compare hypoxia biomarkers and gene expression in oropharyngeal squamous cell carcinoma (OPSCC) diagnostic biopsies with hypoxia imaged with 64Cu-ATSM PET/CT. 64Cu-ATSM imaging, molecular and clinical data were obtained for 15 patients. Primary tumour SUVmax, tumour to muscle ratio (TMR) and hypoxic volume were tested for association with reported hypoxia gene signatures in diagnostic biopsies. A putative gene signature for hypoxia in OPSCCs (hypoxic volume-associated gene signature (HVS)) was derived. [Suh et al. Brit J Cancer (2017) doi: 10.1038/bjc.2017.66]","study_type":"Other","pubmed_ids":[28324887],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002943","title":"FAM50_knockout_phenotype","description":"Melanoma is the most lethal form of skin cancer, with a one year survival of stage IV disease of only fifty percent. S substantial proportion of patients fail to response to currently available treatments. Through a CRISPR dropout screen we have identified a number of synthetic lethal interactions within melanoma. One of these interactions is between two novel genes who's function is unknown. Through knockout of the pair of the genes we are interested in finding the mechanism by which the loss of both genes is lethal to the cell. Through performing RNAseq we hope to gain some insight into the role of these novel genes.","abstract":"Melanoma is the most lethal form of skin cancer, with a one year survival of stage IV disease of only fifty percent. S substantial proportion of patients fail to response to currently available treatments. Through a CRISPR dropout screen we have identified a number of synthetic lethal interactions within melanoma. One of these interactions is between two novel genes who's function is unknown. Through knockout of the pair of the genes we are interested in finding the mechanism by which the loss of both genes is lethal to the cell. Through performing RNAseq we hope to gain some insight into the role of these novel genes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002944","title":"Understanding_Society_GWAS","description":"I am a member of the Health and Biomarker Advisory Committee of the ESRC-funded UK\nHousehold Longitudinal Study (Understanding Society\nhttp://www.understandingsociety.org.uk/). Understanding Society aims to create and enhance\na resource for a wide range of scientists, both social and biological, by combining the\ncollection of biomarkers and psychosocial information with high quality longitudinal social and\neconomic data about individuals and families. Understanding Society has a total target\nsample of 40,000 households/100,000 individuals. DNA samples are currently available for\n13,000 individuals, all with longitudinal data available. The ESRC envisaged from the\nbeginning that USoc would include the collection of health indicators and biomarkers to allow\nfor the study of health in relation to social and biological factors. This funding application\ninvolves genotyping all currently-available study samples on the Illumina backbone array\n(core+exomechip) and then undertaking analysis of cardiometabolic-related traits.","abstract":"I am a member of the Health and Biomarker Advisory Committee of the ESRC-funded UK\nHousehold Longitudinal Study (Understanding Society\nhttp://www.understandingsociety.org.uk/). Understanding Society aims to create and enhance\na resource for a wide range of scientists, both social and biological, by combining the\ncollection of biomarkers and psychosocial information with high quality longitudinal social and\neconomic data about individuals and families. Understanding Society has a total target\nsample of 40,000 households/100,000 individuals. DNA samples are currently available for\n13,000 individuals, all with longitudinal data available. The ESRC envisaged from the\nbeginning that USoc would include the collection of health indicators and biomarkers to allow\nfor the study of health in relation to social and biological factors. This funding application\ninvolves genotyping all currently-available study samples on the Illumina backbone array\n(core+exomechip) and then undertaking analysis of cardiometabolic-related traits.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002945","title":"RNA Sequencing of Colorectal Liver Metastases","description":"A subset of patients with metastatic colorectal cancer achieves prolonged survival after hepatic resection of limited liver metastases. Here, we examined the molecular features of colorectal liver metastases as they relate to clinical outcomes.","abstract":"A subset of patients with metastatic colorectal cancer achieves prolonged survival after hepatic resection of limited liver metastases. Here, we examined the molecular features of colorectal liver metastases as they relate to clinical outcomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-04T21:36:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002946","title":"CellGen_MZG_Voet__Human_post_implantation_embryo_transcriptome","description":"Single-cell SmartSeq2 cDNA Nextera XT libraries from from human post-implantation embryonic cells.","abstract":"Implanting human embryos undergo profound morphological and transcriptional remodelling. However, our understanding of this process is extremely limited because embryos cannot be sampled from the mother. Using our recently developed method to culture human embryos until day 13 we plan to generate a molecular atlas of early human post-implantation development. We will perform a single-cell genomic and transcriptomic characterization with single-cell G&amp;T-seq to study (i) genome instability and the acquisition of somatic genetic variation during early human embryogenesis, (ii) DNA- and RNA-based cell lineage paths, and (iii) fundamental molecular aspects of human embryo development.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002947","title":"The spatio-temporal evolution of lymph node spread in early breast cancer","description":"Purpose: The most significant prognostic factor in early breast cancer is lymph node involvement. This stage between localised and systemic disease is key to understanding breast cancer progression, however our knowledge of the evolution of lymph node malignant invasion remains limited, as most currently available data derive from primary tumours. Experimental design: In 11 treatment-naïve node positive early breast cancer patients without clinical evidence of distant metastasis, we investigated lymph node evolution using spatial multi-region sequencing (n=78 samples) of primary and lymph node deposits and genomic profiling of matched longitudinal circulating tumour DNA (ctDNA). Results: Linear evolution from primary to lymph node was rare (1/11) whereas the majority of cases displayed either early divergence between primary and nodes (4/11), or no detectable divergence (6/11) where both primary and nodal cells belonged to a single recent expansion of a metastatic clone. Divergence of metastatic subclones was driven in part by APOBEC. Longitudinal ctDNA samples from 2 subjects taken peri-operatively reflected the two major evolutionary patterns and demonstrate that private mutations can be detected even from early metastatic nodal deposits. Moreover, node removal resulted in disappearance of private lymph node mutations in ctDNA.Conclusions: This study sheds new light on a crucial evolutionary step in the natural history of breast cancer, demonstrating early establishment of axillary lymph node metastasis in a substantial proportion of patients.","abstract":"Purpose: The most significant prognostic factor in early breast cancer is lymph node involvement. This stage between localised and systemic disease is key to understanding breast cancer progression, however our knowledge of the evolution of lymph node malignant invasion remains limited, as most currently available data derive from primary tumours. Experimental design: In 11 treatment-naïve node positive early breast cancer patients without clinical evidence of distant metastasis, we investigated lymph node evolution using spatial multi-region sequencing (n=78 samples) of primary and lymph node deposits and genomic profiling of matched longitudinal circulating tumour DNA (ctDNA). Results: Linear evolution from primary to lymph node was rare (1/11) whereas the majority of cases displayed either early divergence between primary and nodes (4/11), or no detectable divergence (6/11) where both primary and nodal cells belonged to a single recent expansion of a metastatic clone. Divergence of metastatic subclones was driven in part by APOBEC. Longitudinal ctDNA samples from 2 subjects taken peri-operatively reflected the two major evolutionary patterns and demonstrate that private mutations can be detected even from early metastatic nodal deposits. Moreover, node removal resulted in disappearance of private lymph node mutations in ctDNA.Conclusions: This study sheds new light on a crucial evolutionary step in the natural history of breast cancer, demonstrating early establishment of axillary lymph node metastasis in a substantial proportion of patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-05T10:00:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002948","title":"Lymphoctye_colony_WGS","description":"We study lymphocyte somatic evolution through the sequencing of normal healthy lymphocytes. We perform whole-genome sequencing of single-cell derived T and B cell colonies to identify somatic mutations, and perform targeted deep-sequencing of these mutations. The lineages of T and B cells, and the frequencies of these mutations reveals the neutral and non-neutral evolutionary processes underlying lymphocyte growth and function.","abstract":"As we age, our cells accumulate mutations, termed \"somatic mutations\". Somatic mutations, which exist in mosaic form throughout the body, are a direct record of the evolution of our cells. Some of these mutations are subject to neutral evolution. The study of neutral mutations can reveal the cell lineages resulting from normal development and tissue maintenance, and help us understand key demographic parameter of somatic evolution, such as population size and migration. Other mutations are under selection, resulting in the expansion or contraction of lineages. These mutations can lead to disease, such as cancer; however, the extent of selection on somatic mutations in not understood. We aim to understand the somatic evolution of the primary cells of the adaptive immune system, lymphocytes. As we age, lymphocytes accumulate somatic mutations, which reveal the evolutionary history of lymphocytes, as well as providing information about the particular mutations and lineage structures that contribute to age-related immune disorder. In order to understand somatic evolution in lymphocytes, we sequence lymphocytes from normal, healthy individuals across a range of ages. We perform whole-genome sequencing of single-cell derived T and B cell colonies to identify somatic mutations, and perform targeted deep-sequencing of these mutations. The lineages of T and B cells, and the frequencies of these mutations reveals the neutral and non-neutral evolutionary processes underlying lymphocyte growth.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-05T11:42:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002949","title":"Lymphocyte_colony_TGS","description":"We study lymphocyte somatic evolution through the sequencing of normal healthy lymphocytes. We perform whole-genome sequencing of single-cell derived T and B cell colonies to identify somatic mutations, and perform targeted deep-sequencing of these mutations. The lineages of T and B cells, and the frequencies of these mutations reveals the neutral and non-neutral evolutionary processes underlying lymphocyte growth and function.","abstract":"As we age, our cells accumulate mutations, termed \"somatic mutations\". Somatic mutations, which exist in mosaic form throughout the body, are a direct record of the evolution of our cells. Some of these mutations are subject to neutral evolution. The study of neutral mutations can reveal the cell lineages resulting from normal development and tissue maintenance, and help us understand key demographic parameter of somatic evolution, such as population size and migration. Other mutations are under selection, resulting in the expansion or contraction of lineages. These mutations can lead to disease, such as cancer; however, the extent of selection on somatic mutations in not understood. We aim to understand the somatic evolution of the primary cells of the adaptive immune system, lymphocytes. As we age, lymphocytes accumulate somatic mutations, which reveal the evolutionary history of lymphocytes, as well as providing information about the particular mutations and lineage structures that contribute to age-related immune disorder. In order to understand somatic evolution in lymphocytes, we sequence lymphocytes from normal, healthy individuals across a range of ages. We perform whole-genome sequencing of single-cell derived T and B cell colonies to identify somatic mutations, and perform targeted deep-sequencing of these mutations. The lineages of T and B cells, and the frequencies of these mutations reveals the neutral and non-neutral evolutionary processes underlying lymphocyte growth.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002950","title":"..","description":"..","abstract":"..","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002951","title":"503 genotypes from Inner Asia used in 'Close inbreeding and low genetic diversity in Inner Asian human populations despite geographical exogamy' publication","description":"Inner Asia is particularly interesting to understand human history and evolution, as two groups presenting contrasting cultural traits (notably their language, their social organisation and matrimonial system) cohabit. We sampled 503 individuals from these two groups, belonging to 17 populations from 11 distinct ethnic groups (AltaiKizhi, Kazakh, Khakas, Kyrgyz, Mongolian, Shore, Tajik, Telengit, Tubalar, Turkmen and Uzbek). The samples were then genotyped with 5 different DNA-arrays and, after quality-control, the 253,532 autosomal SNPs present in all the arrays were merged together in the present dataset.","abstract":"Inner Asia is particularly interesting to understand human history and evolution, as two groups presenting contrasting cultural traits (notably their language, their social organisation and matrimonial system) cohabit. We sampled 503 individuals from these two groups, belonging to 17 populations from 11 distinct ethnic groups (AltaiKizhi, Kazakh, Khakas, Kyrgyz, Mongolian, Shore, Tajik, Telengit, Tubalar, Turkmen and Uzbek). The samples were then genotyped with 5 different DNA-arrays and, after quality-control, the 253,532 autosomal SNPs present in all the arrays were merged together in the present dataset.","study_type":"Other","pubmed_ids":[28158897],"external_links":null,"is_released":true,"released_date":"2018-04-05T15:23:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002952","title":"Colorectal advanced adenomas NKI-AvL TGO COCOS series","description":"Colorectal cancer (CRC) develops from normal epithelium, through a benign precursor lesion called adenoma, by accumulation of genetic alterations affecting oncogenes and tumour suppressor genes. About 5% of colorectal adenomas are estimated to progress to CRC. However, it is important to identify which adenomas actually carry a high-risk of progression, because these serve as intermediate endpoints for e.g. screening programs. In clinical practice, adenomas with a size of ≥10 mm, villous component and/or high-grade dysplasia, called advanced adenomas, are considered high-risk, although solid evidence for this classification is lacking. Specific DNA copy number changes are associated with adenoma-to-carcinoma progression.For this tissue dataset, we applied low-pass whole genome sequencing to 96 advanced adenomas. Advanced adenomas were classified as lesions with low-risk or high-risk of progression, according to the presence of specific DNA copy number changes (Carvalho et al, CancerPrevRes, 2018).","abstract":"Colorectal cancer (CRC) develops from normal epithelium, through a benign precursor lesion called adenoma, by accumulation of genetic alterations affecting oncogenes and tumour suppressor genes. About 5% of colorectal adenomas are estimated to progress to CRC. However, it is important to identify which adenomas actually carry a high-risk of progression, because these serve as intermediate endpoints for e.g. screening programs. In clinical practice, adenomas with a size of ≥10 mm, villous component and/or high-grade dysplasia, called advanced adenomas, are considered high-risk, although solid evidence for this classification is lacking. Specific DNA copy number changes are associated with adenoma-to-carcinoma progression.For this tissue dataset, we applied low-pass whole genome sequencing to 96 advanced adenomas. Advanced adenomas were classified as lesions with low-risk or high-risk of progression, according to the presence of specific DNA copy number changes (Carvalho et al, CancerPrevRes, 2018).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-06T08:37:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002953","title":"Colorectal adenomas, NKI-AvL TGO series Stool-Proteomics","description":"Colorectal cancer (CRC) develops from normal epithelium, through a benign precursor lesion called adenoma, by accumulation of genetic alterations affecting oncogenes and tumour suppressor genes. About 5% of colorectal adenomas are estimated to progress to CRC. However, it is important to identify which adenomas actually are at high-risk of progression, because these should serve as intermediate endpoints for e.g. CRC screening programs. In clinical practice, adenomas with a size of ≥10 mm, villous component and/or high-grade dysplasia, called advanced adenomas, are considered high-risk, although this classification lacks solid evidence. Specific DNA copy number changes are associated with adenoma-to-carcinoma progression.For this tissue dataset, we applied low-pass whole genome sequencing to 98 non-advanced and advanced adenomas. These adenomas were classified as lesions with low-risk or high-risk of progression, according to the presence of specific DNA copy number changes (Carvalho et al, CancerPrevRes, 2018).","abstract":"Colorectal cancer (CRC) develops from normal epithelium, through a benign precursor lesion called adenoma, by accumulation of genetic alterations affecting oncogenes and tumour suppressor genes. About 5% of colorectal adenomas are estimated to progress to CRC. However, it is important to identify which adenomas actually are at high-risk of progression, because these should serve as intermediate endpoints for e.g. CRC screening programs. In clinical practice, adenomas with a size of ≥10 mm, villous component and/or high-grade dysplasia, called advanced adenomas, are considered high-risk, although this classification lacks solid evidence. Specific DNA copy number changes are associated with adenoma-to-carcinoma progression.For this tissue dataset, we applied low-pass whole genome sequencing to 98 non-advanced and advanced adenomas. These adenomas were classified as lesions with low-risk or high-risk of progression, according to the presence of specific DNA copy number changes (Carvalho et al, CancerPrevRes, 2018).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-06T11:44:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002954","title":"Whole-genome sequencing reveals genomic signatures associated with the inflammatory microenvironments in Chinese NSCLC patients","description":"Chinese lung cancer patients have distinct epidemiologic and genomic features, highlighting the presence of specific etiologic mechanisms other than smoking. We integrate genomic  (whole-genome sequencing, WGS) and transcriptome (polyA-enriched RNASeq) sequencing from 92 NSCLC cases and comprehensively identified the distinct genomic features of Chinese NSCLC patients. We reveal that inflammatory infiltration may contribute to the accumulation of EGFR mutations, especially in never-smokers.","abstract":"Chinese lung cancer patients have distinct epidemiologic and genomic features, highlighting the presence of specific etiologic mechanisms other than smoking. We integrate genomic  (whole-genome sequencing, WGS) and transcriptome (polyA-enriched RNASeq) sequencing from 92 NSCLC cases and comprehensively identified the distinct genomic features of Chinese NSCLC patients. We reveal that inflammatory infiltration may contribute to the accumulation of EGFR mutations, especially in never-smokers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-09T11:42:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002955","title":"To determine the mutational impact of the in vitro culture, clonal human adult and pluripotent stem cell lines were subjected to a second clonal step after 3 months of culture. These subclones were whole genome sequenced to identify all the mutations that accumulated during the 3 month culture period.","description":"Genetic changes acquired during culture pose a potential risk for the successful application of stem cells. To assess the risk of in vitro expansion on mutation accumulation we have performed whole genome sequencing of clonally expanded human induced pluripotent stem cells (iPS cells) and adult stem cells (ASCs) to identify all mutations that accumulated over a fixed culture period. We find that ASCs acquire more single nucleotide variants (SNVs) and indels per population doubling than the iPS cells. When compared with ASCs, iPS cells are more vulnerable to mutations in genes and promoters. Mutational analysis revealed a clear in vitro induced mutational signature that is irrespective of stem cell type. This in vitro signature is characterized by C to G transversions that are probably caused by oxidative stress. Additionally, we observed stem cell specific mutational signatures and differences in transcriptional strand bias, indicating differential activity of DNA repair mechanisms between stem cell types in culture. In conclusion, in vitro culture induces mutation accumulation in iPS cells and ASCs. Culture under low-oxygen tension may help to reduce the number of culture-induced mutations.","abstract":"Genetic changes acquired during culture pose a potential risk for the successful application of stem cells. To assess the risk of in vitro expansion on mutation accumulation we have performed whole genome sequencing of clonally expanded human induced pluripotent stem cells (iPS cells) and adult stem cells (ASCs) to identify all mutations that accumulated over a fixed culture period. We find that ASCs acquire more single nucleotide variants (SNVs) and indels per population doubling than the iPS cells. When compared with ASCs, iPS cells are more vulnerable to mutations in genes and promoters. Mutational analysis revealed a clear in vitro induced mutational signature that is irrespective of stem cell type. This in vitro signature is characterized by C to G transversions that are probably caused by oxidative stress. Additionally, we observed stem cell specific mutational signatures and differences in transcriptional strand bias, indicating differential activity of DNA repair mechanisms between stem cell types in culture. In conclusion, in vitro culture induces mutation accumulation in iPS cells and ASCs. Culture under low-oxygen tension may help to reduce the number of culture-induced mutations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-10T13:20:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002956","title":"Genomic and transcriptomic characterization of matched primary-relapse diffuse large B-cell lymphoma","description":"Approximately, a third of diffuse large B-cell lymphoma (DLBCL) patients relapse with dismal outcome. Here, we performed a comprehensive genomic and transcriptomic analysis of seven matched primary and relapse DLBCL sample pairs to gain insight into the evolutionary history of relapse in DLBCL. Two patterns governed relapse evolution. A group of patients exhibited late branching relapse and had a dismal outcome, whereas other patients exhibited early branching relapse and had a longer survival. Evolution of the active mutational processes was distinct in each group, with the early branching group having a significant increase in Signature 17 activity after branching. Characterization of mutations and gene expression between primary and relapse samples revealed continuous patient-specific pathway addiction in relapse. These results increase our understanding of DLBCL relapsed disease and have implications on targeted therapies under development.","abstract":"Approximately, a third of diffuse large B-cell lymphoma (DLBCL) patients relapse with dismal outcome. Here, we performed a comprehensive genomic and transcriptomic analysis of seven matched primary and relapse DLBCL sample pairs to gain insight into the evolutionary history of relapse in DLBCL. Two patterns governed relapse evolution. A group of patients exhibited late branching relapse and had a dismal outcome, whereas other patients exhibited early branching relapse and had a longer survival. Evolution of the active mutational processes was distinct in each group, with the early branching group having a significant increase in Signature 17 activity after branching. Characterization of mutations and gene expression between primary and relapse samples revealed continuous patient-specific pathway addiction in relapse. These results increase our understanding of DLBCL relapsed disease and have implications on targeted therapies under development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002957","title":"Multiple esclerosis and mixed microbial infections","description":"This Project deals with the sequencing of ITS1 region, which is highly variable both in length and in nucleotide sequence for different yeast using yeast-specific primers ITS1 and ITS2. A total of 19 samples involving different brain regions from patients with different conditions were analysed. Of these, 10 are controls-healthy patients and 9 multiple sclerosis (MS) patients.","abstract":"This Project deals with the sequencing of ITS1 region, which is highly variable both in length and in nucleotide sequence for different yeast using yeast-specific primers ITS1 and ITS2. A total of 19 samples involving different brain regions from patients with different conditions were analysed. Of these, 10 are controls-healthy patients and 9 multiple sclerosis (MS) patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-11T14:43:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002958","title":"Childhood_arthritis_single_cell_sequencing__Smart_seq2","description":"Here, we will study arthritic cells from children with rheumatoid disease to identify the cell types involved in mediating disease.","abstract":"Here, we will study arthritic cells from children with rheumatoid disease to identify the cell types involved in mediating these disease.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002959","title":"Monitoring ctDNA in low burden cancer to parts per million by integration of variant reads across thousands of mutated loci","description":"These data are from individualised sequencing panels that were applied to plasma samples from patients with melanoma. Multiple mutations were targeted and sequenced at high depth. Using this data, we developed an algorithm called INtegration of VAriant Reads. To validate this method, we generated spike-in dilution series which we applied INVAR to. These samples are available here.","abstract":"These data are from individualised sequencing panels that were applied to plasma samples from patients with melanoma. Multiple mutations were targeted and sequenced at high depth. Using this data, we developed an algorithm called INtegration of VAriant Reads. To validate this method, we generated spike-in dilution series which we applied INVAR to. These samples are available here.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002960","title":"PDL1_validation","description":"Validation of hits from a CRISPR-KO PD-L1 screen will be studied across a range of cell lines using a customised small library of 1000 sgRNAs. Cells will be sorted by FACS 2 weeks after infection, and guides in the PDL1 low/dim population will be compared to unsorted fraction.","abstract":"Validation of hits from a CRISPR-KO PD-L1 screen will be studied across a range of cell lines using a customised small library of 1000 sgRNAs.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002961","title":"WES_Belarus_Immunodeficiency","description":"Whole exome sequencing was used for study a family with two children with combined immunodeficiency and dysregulation","abstract":"Whole exome sequencing was used for study a family with two children with combined immunodeficiency and dysregulation","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002962","title":"WES_of_adult_intellectual_disabilities_with_co_morbid_psychiatric_disorders","description":"ost adults with intellectual disabilities (ID) do not undergo genetic diagnostic investigation as part of their clinical care and have 'missed the boat' with regard to the WES and WGS genetic testing that is now being provided for children with ID. There is a dramatically increased risk of psychistric disorders in adults with ID, e.g. the risk of psychoses is 10X higher than in the general population. It remains an open question as to how much of adult ID is genetic in origin and how similar the genetic forms of adult ID are to those being diagnosed in children, in part due to survivor bias. There is also the opportunity to identify adults with treatable forms of ID, of which over 80 have been described, thus improving their clinical management. Furthermore, analysis of medical records of adults with genetic forms of ID can help to characterise the 'natural history' of individual disorders, resulting in more accurate prognoses for diagnosed children and identifying opportunities for improved management and possibly therapeutic intervention (e.g. optimal anti-epileptic therapy).                                                                           Here we propose to exome sequence (to ~50X coverage) 200 adults with ID and co-morbid psychiatric disorders. This cohort has previously been assayed with chromosomal microarrays (Wolfe et al 2017 EJHG, 25, 66–72) identifying a diagnostic yield of ~11% which is comparable to the CNV diagnostic yield in various child ID cohorts (10-15%). The authors observed no substantive biases in diagnostic yield between different psychiatric diagnostic classes. The WES data will be analysed using the diagnostic workflows developed in the DDD study to ensure comparability between child and adult ID datasets. This study is intended as a pilot study to demonstrate the value of WES in adults with ID.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"ost adults with intellectual disabilities (ID) do not undergo genetic diagnostic investigation as part of their clinical care and have 'missed the boat' with regard to the WES and WGS genetic testing that is now being provided for children with ID. There is a dramatically increased risk of psychistric disorders in adults with ID, e.g. the risk of psychoses is 10X higher than in the general population. It remains an open question as to how much of adult ID is genetic in origin and how similar the genetic forms of adult ID are to those being diagnosed in children, in part due to survivor bias. There is also the opportunity to identify adults with treatable forms of ID, of which over 80 have been described, thus improving their clinical management. Furthermore, analysis of medical records of adults with genetic forms of ID can help to characterise the 'natural history' of individual disorders, resulting in more accurate prognoses for diagnosed children and identifying opportunities for improved management and possibly therapeutic intervention (e.g. optimal anti-epileptic therapy).                                                                           Here we propose to exome sequence (to ~50X coverage) 200 adults with ID and co-morbid psychiatric disorders. This cohort has previously been assayed with chromosomal microarrays (Wolfe et al 2017 EJHG, 25, 66–72) identifying a diagnostic yield of ~11% which is comparable to the CNV diagnostic yield in various child ID cohorts (10-15%). The authors observed no substantive biases in diagnostic yield between different psychiatric diagnostic classes. The WES data will be analysed using the diagnostic workflows developed in the DDD study to ensure comparability between child and adult ID datasets. This study is intended as a pilot study to demonstrate the value of WES in adults with ID.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-17T16:30:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002963","title":"Inference_of_B_cell_clonality_and_function_from_single_cell_RNA_seq_data","description":"cDNA libraries for RNA-seq will be prepared for sequencing. cDNA will be created following the Smart-Seq2 protocol, and a part of the cDNA from each cell will be used for preparation of RNA-seq libraries using the Nextera XT kit. The other part of the cDNA will be used as template for verification of the computationally recovered immunoglobulin sequences from the RNA-seq dataset by using a targeted PCR approach to generate a multiplexed sequencing library","abstract":"To develop a computational method for extracting B cell receptor sequences from single cell RNA-seq data and establish clonal relationships between cells in order to link antigen specificity with the transcriptional profile of B cells. The study aims to demonstrate the use of this method by performing RNA-seq of clonally related autoreactive plasma cells in Coeliac Disease.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-18T11:58:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002964","title":"Pre_clinical_evolution_of_haematological_malignancies","description":"Deep targeted sequencing of 291 peripheral blood samples taken 1-20 years prior diagnosis of a haematological malignancy alongside age- and sex-matched controls. Key objective is to distinguish indolent age-related clonal haematopoiesis from pre-cancer and to derive predictive models for early risk-stratification.","abstract":"Leukaemia and related blood cancers occur due to genetic changes that typically accumulate over many years. This study will employ targeted next-generation sequencing to retrace the preclinical evolution of several types of haematological malignancy.  Investigating the progression of the earliest pre-malignant ancestral clones promises to offer valuable insights into early leukaemia evolution and therapeutic vulnerabilities of leukaemia stem cells.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-18T13:10:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002965","title":"SNP array data for 140 individuals from 5 populations in Pakistan","description":"We have genotyped 140 individuals from 5 populations in Pakistan, using the OmniExpressExome-8 array, which includes approximately one million autosomal SNP markers.","abstract":"We have genotyped 140 individuals from 5 populations in Pakistan, using the OmniExpressExome-8 array, which includes approximately one million autosomal SNP markers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-18T17:59:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002966","title":"Contribution of allelic imbalance to colorectal cancer","description":"Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) landscape in 1699 colorectal cancers, 256 of which have been whole genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge, and unbiased CRISPR-Cas9 knockout and activation screens identified altogether 79 genes within AI peaks regulating cell growth. Genetic and functional data implicates loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point mutations. Importantly, the data reveal several associations between AI target genes, suggesting a role for a network of lineage-determining transcription factors in colorectal tumorigenesis. Overall, the results unravel the contribution of AI in colorectal cancer and provide a plausible explanation why so few genes are commonly affected by point mutations in cancers.","abstract":"Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) landscape in 1699 colorectal cancers, 256 of which have been whole genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge, and unbiased CRISPR-Cas9 knockout and activation screens identified altogether 79 genes within AI peaks regulating cell growth. Genetic and functional data implicates loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point mutations. Importantly, the data reveal several associations between AI target genes, suggesting a role for a network of lineage-determining transcription factors in colorectal tumorigenesis. Overall, the results unravel the contribution of AI in colorectal cancer and provide a plausible explanation why so few genes are commonly affected by point mutations in cancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-19T09:23:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002967","title":"Identification of Therapeutic Targets in Rhabdomyosarcoma Through Integrated Genomic, Epigenomic, and Proteomic Analyses","description":"Personalized cancer therapy based on the somatic mutations identified in patient tumors is becoming an increasingly emphasized approach to improve outcomes of patients with cancer. There are also examples of therapeutic vulnerabilities in cancer that result from changes in gene expression that are a direct or indirect result of tumor specific epigenetic perturbations. These genomic and epigenomic changes are ultimately manifest in the tumor proteome and phosphoproteome.  In this study, we integrated genomic, epigenomic and proteomic data for rhabdomyosarcoma (RMS) to identify therapeutic vulnerabilities. RMS was selected for this analysis because RAS pathway mutations in rhabdomyosarcoma (RMS) are the most common potentially actionable lesions across pediatric solid tumors. The epigenomic data was useful for identifying deregulated developmental pathways in RMS including the WNT, HH, BMP, adenyl cyclase, p38/MAPK and PI3K pathways. Perturbations in those 6 myogenic signal transduction pathways were also evident in the proteome and phosphoteome data. In addition, the proteomic/phosphoproteomic data revealed that the cell cycle checkpoint, unfolded protein response and RB/E2F pathways were deregulated in RMS relative to normal muscle. Recent success targeting CDK4/6 and MEK in adult cancers with RAS mutations led us to test the value of these targets in RMS tumors. We also targeted the unfolded protein response pathway and cell cycle checkpoint pathway using molecular targeted therapeutics in orthotopic patient derived xenografts. Taken together, these data demonstrate the value of integrating epigenomic and proteomic data to identify tumor vulnerabilities that extend beyond somatic mutations identified in the genome.","abstract":"Personalized cancer therapy based on the somatic mutations identified in patient tumors is becoming an increasingly emphasized approach to improve outcomes of patients with cancer. There are also examples of therapeutic vulnerabilities in cancer that result from changes in gene expression that are a direct or indirect result of tumor specific epigenetic perturbations. These genomic and epigenomic changes are ultimately manifest in the tumor proteome and phosphoproteome.  In this study, we integrated genomic, epigenomic and proteomic data for rhabdomyosarcoma (RMS) to identify therapeutic vulnerabilities. RMS was selected for this analysis because RAS pathway mutations in rhabdomyosarcoma (RMS) are the most common potentially actionable lesions across pediatric solid tumors. The epigenomic data was useful for identifying deregulated developmental pathways in RMS including the WNT, HH, BMP, adenyl cyclase, p38/MAPK and PI3K pathways. Perturbations in those 6 myogenic signal transduction pathways were also evident in the proteome and phosphoteome data. In addition, the proteomic/phosphoproteomic data revealed that the cell cycle checkpoint, unfolded protein response and RB/E2F pathways were deregulated in RMS relative to normal muscle. Recent success targeting CDK4/6 and MEK in adult cancers with RAS mutations led us to test the value of these targets in RMS tumors. We also targeted the unfolded protein response pathway and cell cycle checkpoint pathway using molecular targeted therapeutics in orthotopic patient derived xenografts. Taken together, these data demonstrate the value of integrating epigenomic and proteomic data to identify tumor vulnerabilities that extend beyond somatic mutations identified in the genome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-20T00:58:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002968","title":"Genomic landscape of IG-MYC positive Burkitt lymphoma with precursor B-cell immunophenotype.","description":"As part of the ICGC, the ICGC MMML-Seq project performed whole genome sequencing of a rare Burkitt lymphoma subtype with precursor B-cell immunophenotype. Analysis were performed in concordance with the guidelines of the ICGC.","abstract":"As part of the ICGC, the ICGC MMML-Seq project performed whole genome sequencing of a rare Burkitt lymphoma subtype with precursor B-cell immunophenotype. Analysis were performed in concordance with the guidelines of the ICGC.","study_type":"Other","pubmed_ids":[30282799],"external_links":null,"is_released":true,"released_date":"2018-04-20T09:33:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002969","title":"HELIUS cohort","description":"The gut microbiota composition is unique to every individual but is shaped by common factors including diet, lifestyle, medication use, early-life determinants, living environment or genetics. Most of these factors may be influenced by ethnicity. This study explored variations in fecal microbiota composition in 6048 individuals with different ethnic backgrounds living in the same geographical area (Amsterdam, the Netherlands).\n\nThe HELIUS data are owned by the Amsterdam University Medical Centers, location AMC in Amsterdam, The Netherlands. To allow sharing of microbiome data collected in HELIUS with (inter)national researchers, 16s rRNA sequence analysis has been stored at the European genome-phenome archive (EGA; accession code EGAD00001004106). This requires that access needs to be granted, also because the HELIUS data are stored with relevant phenotypical variables. Access is granted to all researchers affiliated with an internationally recognized research institution who request to use the HELIUS data within the EGA context, after having signed the data transfer agreement. Any researcher can request the data by submitting a proposal to the HELIUS Executive Board as outlined at http://www.heliusstudy.nl/en/researchers/collaboration, by email: heliuscoordinator at amsterdamumc dot nl. The HELIUS Executive Board will check proposals if they do not conflict with ethical approvals and informed consent forms of the HELIUS study.","abstract":"The gut microbiota composition is unique to every individual but is shaped by common factors including diet, lifestyle, medication use, early-life determinants, living environment or genetics. Most of these factors may be influenced by ethnicity. This study explored variations in fecal microbiota composition in 6048 individuals with different ethnic backgrounds living in the same geographical area (Amsterdam, the Netherlands).\n\nThe HELIUS data are owned by the Amsterdam University Medical Centers, location AMC in Amsterdam, The Netherlands. To allow sharing of microbiome data collected in HELIUS with (inter)national researchers, 16s rRNA sequence analysis has been stored at the European genome-phenome archive (EGA; accession code EGAD00001004106). This requires that access needs to be granted, also because the HELIUS data are stored with relevant phenotypical variables. Access is granted to all researchers affiliated with an internationally recognized research institution who request to use the HELIUS data within the EGA context, after having signed the data transfer agreement. Any researcher can request the data by submitting a proposal to the HELIUS Executive Board as outlined at http://www.heliusstudy.nl/en/researchers/collaboration, by email: heliuscoordinator at amsterdamumc dot nl. The HELIUS Executive Board will check proposals if they do not conflict with ethical approvals and informed consent forms of the HELIUS study.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-20T19:02:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002970","title":"RNA-seq profiling of primary Malignant Rhabdoid Tumours","description":"An observational experiment to expression profile 23 SMARCB1 negative primary tumours from patients diagnosed with Malignant Rhabdoid Tumours. Total RNA was paired-end sequenced on an illumina platform aiming for ~90M reads. Sequences were aligned, reads counted and normalised and the resulting expression profiles used to characterise a SMARCB1 negative (MRT) expression signature. Profiles were also used as a means to identify expression differences related to bodily location.","abstract":"An observational experiment to expression profile 23 SMARCB1 negative primary tumours from patients diagnosed with Malignant Rhabdoid Tumours. Total RNA was paired-end sequenced on an illumina platform aiming for ~90M reads. Sequences were aligned, reads counted and normalised and the resulting expression profiles used to characterise a SMARCB1 negative (MRT) expression signature. Profiles were also used as a means to identify expression differences related to bodily location.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002971","title":"Transcriptional_analysis_of_haematopoietic_cells","description":"To capture the full heterogeneity of the cellular types and states during human HSPCs differentiation, haematopoietic progenitors will be processed using the 10x Genomics platform. \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This program of work will determine the transcriptional changes during the development of haematopoietic cells. Single-cell RNA-Seq of thousands of blood cells combined with the state-of-the art computational analysis will provide unparalleled insight into the mechanisms and pathways of haematopoietic cells differentiation and development.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002972","title":"Single cell exome sequencing of lung adenocarcinoma","description":"Single cell exome sequencing was performed on 200 single cells isolated from a lung adenocarcinoma, female, non-smoker patient. The cells were derived from two distant tumour sectors and a far normal sector. The single cells were amplified on the Fluidigm C1 machine using the GE Healthcare illustra GenomiPhi V2 DNA Amplification Kit prior to sequencing library preparation. In addition, bulk exome sequencing was also conducted for each tumour sectors. For this study, somatic variations were detected from the single cells and phylogenetic clustering was conducted to elucidate the evolutionary trajectory of lung cancer.","abstract":"Single cell exome sequencing was performed on 200 single cells isolated from a lung adenocarcinoma, female, non-smoker patient. The cells were derived from two distant tumour sectors and a far normal sector. The single cells were amplified on the Fluidigm C1 machine using the GE Healthcare illustra GenomiPhi V2 DNA Amplification Kit prior to sequencing library preparation. In addition, bulk exome sequencing was also conducted for each tumour sectors. For this study, somatic variations were detected from the single cells and phylogenetic clustering was conducted to elucidate the evolutionary trajectory of lung cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-24T09:39:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002973","title":"Assess_IPSC_pool_stability_in_culture","description":"The impact of genetic variants on molecular pathways that give rise to neurodegenerative diseases such as Alzheimer’s and Parkinson’s is best elucidated in the appropriate cell types and molecular contexts. Existing studies have focused on bulk profiling of mixed cell types, but have ignored assaying genetic effects across development and cell differentiation. At the core of this proposal is the idea to carry out differentiation process for &gt;100 selected lines toward IPSC-derived dopaminergic neurons in order to identify genetic variants that could identify subjects with the highest risk for the development of sporadic PD. Cell lines will be pooled before differentiation, and pool stability will be assessed at different time points of the differentiation.","abstract":"The impact of genetic variants on molecular pathways that give rise to neurodegenerative diseases such as Alzheimer’s and Parkinson’s is best elucidated in the appropriate cell types and molecular contexts. Existing studies have focused on bulk profiling of mixed cell types, but have ignored assaying genetic effects across development and cell differentiation. At the core of this proposal is the idea to carry out differentiation process for &gt;100 selected lines toward IPSC-derived dopaminergic neurons in order to identify genetic variants that could identify subjects with the highest risk for the development of sporadic PD. Cell lines will be pooled before differentiation, and pool stability will be assessed at different time points of the differentiation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002974","title":"iNeurons","description":"We are sequencing the BOB-iNeuron and THP-1 cell lines in order to gain accurate sequence data of the entire genome (including non-coding regions) including haplotype information to allow the better design of CRISPR reagents and homology constructs for introducing SNPs and other defined genomic changes .  \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We are sequencing the BOB-iNeuron and THP-1 cell lines in order to gain accurate sequence data of the entire genome (including non-coding regions) including haplotype information to allow the better design of CRISPR reagents and homology constructs for introducing SNPs and other defined genomic changes. This data will be critical  to ascertain the genetic background that we are using to introduce genome edits that will allow the study of SNPs contributing to AD and PD pathogenesis.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002975","title":"A genome scan for genes underlying adult body size differences between Central African hunter-gatherers and farmers.","description":"The evolutionary and biological bases of the Central African pygmy phenotype, a characteristic of rainforest huntergatherers defined by reduced body size compared with neighboring farmers, remain largely unknown. Here, we perform a joint investigation in Central African hunter-gatherers and farmers of adult standing height, sitting height, leg length, and body mass index (BMI), considering 358 hunter-gatherers and 169 farmers with genotypes for 153,798 SNPs. In addition to reduced standing heights, hunter-gatherers have shorter sitting heights and leg lengths and higher sitting/standing height ratios than farmers and lower BMI for males. Standing height, sitting height, and leg length are strongly correlated with inferred levels of farmer genetic ancestry, whereas BMI is only weakly correlated, perhaps reflecting greater contributions of non-genetic factors to body weight than to height. Single- and multi-marker association tests identify one region and eight genes associated with hunter-gatherer/farmer status, and 24 genes associated with the height-related traits. Many of these genes have putative functions consistent with roles in determining their associated traits and the pygmy phenotype, and they include three associated with standing height in non-Africans (PRKG1, DSCAM, MAGI2). We find evidence that European height-associated SNPs or variants in linkage disequilibrium with them contribute to standing- and sitting-height determination in Central Africans, but not to the differential status of hunter-gatherers and farmers. These findings provide new insights into the biological basis of the pygmy phenotype, and they highlight the potential of cross-population studies for exploring the genetic basis of phenotypes that vary naturally across populations.\nPemberton et al. Human Genetics 2018\nhttps://doi.org/10.1007/s00439-018-1902-3","abstract":"The evolutionary and biological bases of the Central African pygmy phenotype, a characteristic of rainforest huntergatherers defined by reduced body size compared with neighboring farmers, remain largely unknown. Here, we perform a joint investigation in Central African hunter-gatherers and farmers of adult standing height, sitting height, leg length, and body mass index (BMI), considering 358 hunter-gatherers and 169 farmers with genotypes for 153,798 SNPs. In addition to reduced standing heights, hunter-gatherers have shorter sitting heights and leg lengths and higher sitting/standing height ratios than farmers and lower BMI for males. Standing height, sitting height, and leg length are strongly correlated with inferred levels of farmer genetic ancestry, whereas BMI is only weakly correlated, perhaps reflecting greater contributions of non-genetic factors to body weight than to height. Single- and multi-marker association tests identify one region and eight genes associated with hunter-gatherer/farmer status, and 24 genes associated with the height-related traits. Many of these genes have putative functions consistent with roles in determining their associated traits and the pygmy phenotype, and they include three associated with standing height in non-Africans (PRKG1, DSCAM, MAGI2). We find evidence that European height-associated SNPs or variants in linkage disequilibrium with them contribute to standing- and sitting-height determination in Central Africans, but not to the differential status of hunter-gatherers and farmers. These findings provide new insights into the biological basis of the pygmy phenotype, and they highlight the potential of cross-population studies for exploring the genetic basis of phenotypes that vary naturally across populations.\nPemberton et al. Human Genetics 2018\nhttps://doi.org/10.1007/s00439-018-1902-3","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-25T14:14:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002976","title":"H3Africa Chip Design - Aim of designing a cost-effective GWAS chip with content appropriate for use in genomics studies of individuals from the African continent.","description":"Since it is recognized that currently available chips may not be ideally suited to studying African populations, the H3Africa Genome Analysis working group undertook the task of designing a cost-effective GWAS chip with content appropriate for use in genomics research studies of individuals from the African continent. To address gaps in sequence data for some of the African populations being studied in H3Africa projects, a high coverage whole genome sequence dataset was generated at the Baylor College of Medicine with samples provided by H3Africa PIs and collaborators, funded by the National Institutes of Health. This dataset includes 350 high coverage and 160 medium coverage whole genome sequences from 348 populations. The data is accompanied by minimal metadata, including country, ethnic group and sex.","abstract":"Since it is recognized that currently available chips may not be ideally suited to studying African populations, the H3Africa Genome Analysis working group undertook the task of designing a cost-effective GWAS chip with content appropriate for use in genomics research studies of individuals from the African continent. To address gaps in sequence data for some of the African populations being studied in H3Africa projects, a high coverage whole genome sequence dataset was generated at the Baylor College of Medicine with samples provided by H3Africa PIs and collaborators, funded by the National Institutes of Health. This dataset includes 350 high coverage and 160 medium coverage whole genome sequences from 348 populations. The data is accompanied by minimal metadata, including country, ethnic group and sex.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-26T11:25:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002977","title":"Targeted sequencing about core genes involved in telomere biology in colorectal cancer patients","description":"We sequenced the coding exons of core genes involved in telomere maintenance using peripheral blood DNA of 192 CRC patients. The primary sequencing data were generated by using Ion Torrent Personal Genome Machine® (PGM™) platform (Life Technologies, Carlsbad, CA, USA).","abstract":"We sequenced the coding exons of core genes involved in telomere maintenance using peripheral blood DNA of 192 CRC patients. The primary sequencing data were generated by using Ion Torrent Personal Genome Machine® (PGM™) platform (Life Technologies, Carlsbad, CA, USA).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-27T04:04:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002978","title":"A_systems_biology_approach_to_understand_immunity_and_pathogenesis_of_malaria_in_children_exposed_to_endemic_Plasmodium_falciparum_transmission","description":"From long-term studies of children in Kenya, we know that some children have numerous malaria episodes through to older age, while other children become immune more rapidly. Our hypothesis is that these children with frequent malaria episodes are caught in a vicious circle, whereby malaria episodes lead to impaired immunity to malaria, which in turn leads to further episodes of malaria. We will therefore investigate immune responses in children with different life histories of malaria episodes. We will also include a group of children living in similar environmental conditions but who are completely unexposed to malaria.  Aims: Using RNAseq we will characterise the transcriptome of a group of children with frequent and febrile malaria or infrequent/asymptomatic. These data will be combined with cytokine profiling data (NIMR) and used to build predictive models (Exeter). The predictions will be validated against a similar second group. A single snap shot of immune responses may represent only the endpoint of many immune processes and may not reflect those that are causally related to differences in malaria outcome. Therefore, we will collect and store samples from a larger group of children who will then be followed up for over 3-4 years. This extended follow up will allow us to identify the same groups as described above, and then examine samples taken before the development of those outcomes. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"From long-term studies of children in Kenya, we know that some children have numerous malaria episodes through to older age, while other children become immune more rapidly. Our hypothesis is that these children with frequent malaria episodes are caught in a vicious circle, whereby malaria episodes lead to impaired immunity to malaria, which in turn leads to further episodes of malaria. We will therefore investigate immune responses in children with different life histories of malaria episodes. We will also include a group of children living in similar environmental conditions but who are completely unexposed to malaria.  Aims: Using RNAseq we will characterise the transcriptome of a group of children with frequent and febrile malaria or infrequent/asymptomatic. These data will be combined with cytokine profiling data (NIMR) and used to build predictive models (Exeter). The predictions will be validated against a similar second group. A single snap shot of immune responses may represent only the endpoint of many immune processes and may not reflect those that are causally related to differences in malaria outcome. Therefore, we will collect and store samples from a larger group of children who will then be followed up for over 3-4 years. This extended follow up will allow us to identify the same groups as described above, and then examine samples taken before the development of those outcomes. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-27T14:36:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002979","title":"Targeted sequencing of head and neck squamous cell carcinomas","description":"Overall survival remains very poor for patients diagnosed with head and neck squamous cell carcinoma (HNSCC). Identification of additional biomarkers and novel therapeutic strategies are important for improving patient outcome. Patient-derived xenografts (PDXs), generated by implanting fresh tumor tissue directly from patients into immune-deficient mice, recapitulate many of the features of their corresponding clinical cancers, including histopathological and molecular profiles. Using a large collection of PDX models of HNSCC we demonstrate that rapid engraftment into immune-compromised mice is highly prognostic, and show that genomic deregulation of the G1/S checkpoint pathway correlates with engraftment. Furthermore, CCND1 and CDKN2A genomic alterations are predictive of response to the CDK4/6 inhibitor abemaciclib. Overall, our study supports the pursuit of CDK4/6 inhibitors as a therapeutic strategy for a substantial proportion of HNSCC patients, and demonstrates the potential of using PDX models to identify novel targeted therapies for those patients who have the poorest outcomes.","abstract":"Overall survival remains very poor for patients diagnosed with head and neck squamous cell carcinoma (HNSCC). Identification of additional biomarkers and novel therapeutic strategies are important for improving patient outcome. Patient-derived xenografts (PDXs), generated by implanting fresh tumor tissue directly from patients into immune-deficient mice, recapitulate many of the features of their corresponding clinical cancers, including histopathological and molecular profiles. Using a large collection of PDX models of HNSCC we demonstrate that rapid engraftment into immune-compromised mice is highly prognostic, and show that genomic deregulation of the G1/S checkpoint pathway correlates with engraftment. Furthermore, CCND1 and CDKN2A genomic alterations are predictive of response to the CDK4/6 inhibitor abemaciclib. Overall, our study supports the pursuit of CDK4/6 inhibitors as a therapeutic strategy for a substantial proportion of HNSCC patients, and demonstrates the potential of using PDX models to identify novel targeted therapies for those patients who have the poorest outcomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-27T14:51:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002980","title":"RNAseq of Follicular Lymphoma","description":"RNAseq analysis of 28 Follicular Lymphoma (FL) criopreserved samples was performed using ribosomal-depleted total RNA to analyze long non-coding RNA and coding transcript expression profiles comparing two different histological groups of FL tumors (FL1-3A versus FL3B/DLBCL). These comparisons were performed either in a subset of tumor purified cell samples (N=12) as in unpurified tumor samples including normal cells for the lymph node microenvironment (N=16).","abstract":"RNAseq analysis of 28 Follicular Lymphoma (FL) criopreserved samples was performed using ribosomal-depleted total RNA to analyze long non-coding RNA and coding transcript expression profiles comparing two different histological groups of FL tumors (FL1-3A versus FL3B/DLBCL). These comparisons were performed either in a subset of tumor purified cell samples (N=12) as in unpurified tumor samples including normal cells for the lymph node microenvironment (N=16).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-28T09:19:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002981","title":"RNA-seq analysis of human primary keratinocytes and skin","description":"Bulk and single cell RNA-seq analysis of human keratinocyte and human skin","abstract":"Bulk and single cell RNA-seq analysis of human keratinocyte and human skin","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-04-28T17:48:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002982","title":"cis-Var: a computational approach for discovery of regulatory non-coding variants in cancer genomes","description":"cis-Var was developed to identify somatic non-coding variants in cancer that cause aberrant cis-regulation of gene transcription. Integrating whole genome and transcriptome sequencing data, cis-Var computes outlier allelic specific expression (ASE) status as the signature of transcriptionally dysregulated genes; causal non-coding variants are then identified via analysis of transcription factor binding motifs and 3D genome architecture. A pilot study of 22 T-lineage acute lymphoblastic leukemias (T-ALL) detected not only all known activating non-coding variants, but also a novel recurrent variant predicted to activate the TAL1 oncogene by forming a new enhancer, a finding validated in vivo by ChIP-seq of a patient-derived xenograft (PDX). Furthermore, we discovered two novel T-ALL genes, LMO3 and PRLR, which were cis-activated by a novel intergenic SV and a focal deletion, respectively. These results demonstrate that cis-Var is a powerful method for improving our understanding of the effects of non-coding somatic variants on oncogenic regulation.","abstract":"cis-Var was developed to identify somatic non-coding variants in cancer that cause aberrant cis-regulation of gene transcription. Integrating whole genome and transcriptome sequencing data, cis-Var computes outlier allelic specific expression (ASE) status as the signature of transcriptionally dysregulated genes; causal non-coding variants are then identified via analysis of transcription factor binding motifs and 3D genome architecture. A pilot study of 22 T-lineage acute lymphoblastic leukemias (T-ALL) detected not only all known activating non-coding variants, but also a novel recurrent variant predicted to activate the TAL1 oncogene by forming a new enhancer, a finding validated in vivo by ChIP-seq of a patient-derived xenograft (PDX). Furthermore, we discovered two novel T-ALL genes, LMO3 and PRLR, which were cis-activated by a novel intergenic SV and a focal deletion, respectively. These results demonstrate that cis-Var is a powerful method for improving our understanding of the effects of non-coding somatic variants on oncogenic regulation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002983","title":"Identification of the mutational consequences of precancerous liver disease (including alcohol abuse) on the genomes of human adult stem cells.","description":"Stem cells are believed to be the cells-of-origin cancer. Nevertheless, their genome remains remarkably stable during life. To increase insight into how these cells can drive tumorigenesis, we set out to determine the genomic integrity of human adult stem cells from patients with liver disease associated with increased cancer risk. To this end, we characterized genome-wide mutation profiles of single ASCs from livers of patients with alcoholic liver disease, non-alcoholic liver disease and primary sclerosing cholangitis. The patients included in our study received a liver transplant due to their liver disease. Strikingly, we found that ASCs in these livers maintain a stable genome and have comparable mutation rates as healthy human liver ASCs. We did observe more nonsense and nonsynonymous mutations in COSMIC cancer genes that are hit by dominant mutations in tumors in comparison to healthy ASCs (n.s.), including two ASCs in alcoholic liver disease patients with a nonsense mutation in PTPRK. Next, we sequenced 5 biopsies of an alcoholic tumour to identify the mutational patterns in the tumour-initiating ASC. We found that the mutational patterns are, again, similar to healthy liver, but the mutational load is slightly higher. This suggests that the increased cancer risk in the liver disease patients is not caused by an increased mutational load, but rather that the precancerous liver environment promotes outgrowth of cells that would normally be selected against.","abstract":"Stem cells are believed to be the cells-of-origin cancer. Nevertheless, their genome remains remarkably stable during life. To increase insight into how these cells can drive tumorigenesis, we set out to determine the genomic integrity of human adult stem cells from patients with liver disease associated with increased cancer risk. To this end, we characterized genome-wide mutation profiles of single ASCs from livers of patients with alcoholic liver disease, non-alcoholic liver disease and primary sclerosing cholangitis. The patients included in our study received a liver transplant due to their liver disease. Strikingly, we found that ASCs in these livers maintain a stable genome and have comparable mutation rates as healthy human liver ASCs. We did observe more nonsense and nonsynonymous mutations in COSMIC cancer genes that are hit by dominant mutations in tumors in comparison to healthy ASCs (n.s.), including two ASCs in alcoholic liver disease patients with a nonsense mutation in PTPRK. Next, we sequenced 5 biopsies of an alcoholic tumour to identify the mutational patterns in the tumour-initiating ASC. We found that the mutational patterns are, again, similar to healthy liver, but the mutational load is slightly higher. This suggests that the increased cancer risk in the liver disease patients is not caused by an increased mutational load, but rather that the precancerous liver environment promotes outgrowth of cells that would normally be selected against.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-02T10:10:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002984","title":"Sequencing_of_patient_samples_who_received_immune_checkpoint_inhibition___RNAseq___NKI","description":"DNA and RNA isolated from FFPE blocks of patients who received immune checkpoint inhibition (ICI) are sequenced with the aim to identify therapeutically tractable vulnerabilities in tumors to prevent ICI resistance.","abstract":"The clinical outcome of late-stage melanoma patients has greatly improved thanks to the recent availability of targeted therapy and T cell checkpoint modulation, primarily CTLA-4 and PD-1/PD-L1 blockade. Also, for advanced non-small cell lung cancer, anti-PD-(L)1 antibody prolongs patient survival and has therefore been approved as first- and second-line treatments. Despite these advances, however, for immune checkpoint inhibition (ICI) of both these cancer types, most patients fail to (durably) benefit mainly because of primary, adaptive, and acquired therapy resistance. Crucially, our understanding of the underlying mechanisms of ICI resistance is only fragmentary, as is our ability to predict which patients are likely to fail on to therapy. We will analyse the RNA/DNA sequence data to increase our understanding of (acquired-) resistance and with the aim to identify therapeutically tractable vulnerabilities in tumors to prevent ICI resistance.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002985","title":"Osteosarcoma mate-pair and RNA-sequencing","description":"DNA mate pair and RNA sequencing data of conventional osteosarcomas. Mate pair libraries, with average insert sizes of 2-4 kb, were prepared for sequencing using the Nextera Mate Pair Library Preparation Kit. Paired-end 76 base pair reads were generated using an Illumina NextSeq 500 sequencing instrument. Total RNA was enriched for polyadenylated RNA using magnetic oligo(dT) beads. Enriched RNA was prepared for sequencing using the TruSeq RNA Sample Preparation Kit v2 and paired-end 151 base pair reads were generated from the cDNA libraries using an Illumina NextSeq 500 instrument.","abstract":"DNA mate pair and RNA sequencing data of conventional osteosarcomas. Mate pair libraries, with average insert sizes of 2-4 kb, were prepared for sequencing using the Nextera Mate Pair Library Preparation Kit. Paired-end 76 base pair reads were generated using an Illumina NextSeq 500 sequencing instrument. Total RNA was enriched for polyadenylated RNA using magnetic oligo(dT) beads. Enriched RNA was prepared for sequencing using the TruSeq RNA Sample Preparation Kit v2 and paired-end 151 base pair reads were generated from the cDNA libraries using an Illumina NextSeq 500 instrument.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002986","title":"Exploring rare and low-frequency variants in the Saguenay–Lac-Saint-Jean population identified genes associated with asthma and allergy related traits","description":null,"abstract":"The Saguenay–Lac-Saint-Jean (SLSJ) region is located in northeastern Quebec and is known for its unique demographic history and founder effect. Since founder populations are enriched in population-specific variants, we first assessed differences in variant distribution and characteristics between this population and the Finnish founder population along with three other European populations (Sweden, United Kingdom and France). We then explored the advantages of using the SLSJ population in the study of rare coding and noncoding regulatory variants in complex traits such as asthma and allergies. We used targeted sequencing of coding and non-coding regulatory regions of immune cells on 149 trios from the SLSJ asthma familial cohort and on samples from the four European populations. Although the founder populations do not appear to have more rare or deleterious variants, we observed that a larger proportion of population-specific variants reached higher frequencies and that low-frequency variants appear to be more deleterious. Thus, a substantial number of variants specific to these populations can be tested in the context of complex traits. Genotypes were then inferred and imputed for the rest of the SLSJ cohort (1 214 samples) and used in single variant association and gene-based tests on asthma and allergy related-traits: eosinophil percentage, immunoglobulin (Ig)E levels and lung function. Using a founder population like the SLSJ allowed us to identify four new genes associated with asthma and allergy-related traits. This may help better understand the genes and pathways implicated in the development of the pathophysiology.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002987","title":"The whole blood of female volunteers and sperm from the male volunteer were used to extract genomic DNA to do whole genome sequencing. Distinguished SNPs between parental genomes were retained to analyze parental allele-specific DNA methylation and chromatin accessibility in scCOOL-seq data.","description":"DNA methylation, chromatin states, and their interrelationships represent critical epigenetic information, but those are largely unknown in human early embryos. Here, we apply scCOOL-seq (Chromatin Overall Omic-scale Landscape Sequencing) to generate a genome-wide map of DNA methylation and chromatin accessibility at single-cell resolution during human preimplantation development. Unlike in mice, the chromatin of paternal genome is already more open than that of maternal genome at the mid-zygote stage in humans, and this state is maintained until the 4-cell stage. After fertilization, genes with high variations in DNA methylation and those with high variations in chromatin accessibility tend to be two different sets. Furthermore, 1,797 (35%) out of 5,155 widely open chromatin regions in promoters closed when transcription activity was inhibited, indicating a feedback mechanism between transcription and open chromatin maintenance. Our work paves the way for dissecting the complex, yet highly coordinated, epigenetic reprogramming during human preimplantation development.","abstract":"DNA methylation, chromatin states, and their interrelationships represent critical epigenetic information, but those are largely unknown in human early embryos. Here, we apply scCOOL-seq (Chromatin Overall Omic-scale Landscape Sequencing) to generate a genome-wide map of DNA methylation and chromatin accessibility at single-cell resolution during human preimplantation development. Unlike in mice, the chromatin of paternal genome is already more open than that of maternal genome at the mid-zygote stage in humans, and this state is maintained until the 4-cell stage. After fertilization, genes with high variations in DNA methylation and those with high variations in chromatin accessibility tend to be two different sets. Furthermore, 1,797 (35%) out of 5,155 widely open chromatin regions in promoters closed when transcription activity was inhibited, indicating a feedback mechanism between transcription and open chromatin maintenance. Our work paves the way for dissecting the complex, yet highly coordinated, epigenetic reprogramming during human preimplantation development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-03T07:44:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002988","title":"Role_of_HPV_and_Interferon_in_APOBEC_mutational_signature","description":"The aim of this project is to test whether HPV oncogenes and /or interferon induce the APOBEC mutational signature in vitro, and to test the role of APOBEC3A in this process.","abstract":"The aim of this project is to test whether HPV oncogenes and /or interferon induce the APOBEC mutational signature in vitro, and to test the role of APOBEC3A in this process.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-03T13:49:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002989","title":"Human_PSC_derived_BAT_RNAseq_Analysis","description":"Obesity and associated metabolic complications are major health problems. Here we propose a strategy focused on targeting the mechanisms controlling energy dissipation to create negative energy balance. The brown adipose tissue (BAT) is specialised in energy dissipation in response to environmental stimuli such as cold and increased lipid rich hypercaloric intake, a process referred as adaptive thermogenesis. This energy dissipating role of BAT is mediated by uncoupling protein 1 (UCP1). The relevance of BAT activation to energy balance is well established in murine models. The realisation that functional BAT is also found in adult humans is much more recent. An inverse relationship between adiposity, diabetes and BAT activity has been observed. These results support the concept that increasing a) BAT mass, b) activity o c) recruitment of beige cells could be a safe and efficient strategy to prevent or treat obesity and its associated complications. Current cellular and developmental models of adipogenesis have limited therapeutic potential and constrains the discovery of cell fate mechanisms involved in human BAT development. To surmount these issues, human pluripotent stem cells (PSCs) in vitro differentiation represents a promising complementary model of brown adipogenesis.\nWithin the pump-priming project “ES/IPS cells differentiation to brown/beige adipocytes as an anti-obesity strategy”, we developed a model of human PSC-derived brown adipose tissue progenitors (mesodermal, early, late progenitors) and of mature brown adipocyte.     \n\n This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Obesity and associated metabolic complications are major health problems. Here we propose a strategy focused on targeting the mechanisms controlling energy dissipation to create negative energy balance. The brown adipose tissue (BAT) is specialised in energy dissipation in response to environmental stimuli such as cold and increased lipid rich hypercaloric intake, a process referred as adaptive thermogenesis. This energy dissipating role of BAT is mediated by uncoupling protein 1 (UCP1). The relevance of BAT activation to energy balance is well established in murine models. The realisation that functional BAT is also found in adult humans is much more recent. An inverse relationship between adiposity, diabetes and BAT activity has been observed. These results support the concept that increasing a) BAT mass, b) activity o c) recruitment of beige cells could be a safe and efficient strategy to prevent or treat obesity and its associated complications. Current cellular and developmental models of adipogenesis have limited therapeutic potential and constrains the discovery of cell fate mechanisms involved in human BAT development. To surmount these issues, human pluripotent stem cells (PSCs) in vitro differentiation represents a promising complementary model of brown adipogenesis.\nWithin the pump-priming project “ES/IPS cells differentiation to brown/beige adipocytes as an anti-obesity strategy”, we developed a model of human PSC-derived brown adipose tissue progenitors (mesodermal, early, late progenitors) and of mature brown adipocyte.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002990","title":"Aneurysmal Subarachnoid hemorrhage patients with or without vasospasm","description":"The shared data include normalized miRNA data in aneurysmal Subarachnoid hemorrhage patients with or without vasospasm","abstract":"The shared data include normalized miRNA data in aneurysmal Subarachnoid hemorrhage patients with or without vasospasm","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002991","title":"Interethnic comparability in blood pressure GWAS","description":"We carried out a genome-wide association and replication study for blood pressure in a two-stage approach (max N = 289,038) with a discovery stage sample of 130,777 East Asian individuals, identifying 19 new genetic loci. We found a significant genetic heterogeneity between East Asian and European-descent populations at several blood pressure loci, conforming to “a common ancestry-specific variant association model”. At 6 unique loci, distinct non-rare (or common) ancestry-specific variants co-localized within the same linkage disequilibrium block despite the significantly discordant direction of effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect sizes is 0.898 and 0.851 for systolic and diastolic blood pressure, respectively. Some of the ancestry-specific association signals were also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in the occurrence of ethnic differences in complex traits such as blood pressure.","abstract":"We carried out a genome-wide association and replication study for blood pressure in a two-stage approach (max N = 289,038) with a discovery stage sample of 130,777 East Asian individuals, identifying 19 new genetic loci. We found a significant genetic heterogeneity between East Asian and European-descent populations at several blood pressure loci, conforming to “a common ancestry-specific variant association model”. At 6 unique loci, distinct non-rare (or common) ancestry-specific variants co-localized within the same linkage disequilibrium block despite the significantly discordant direction of effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect sizes is 0.898 and 0.851 for systolic and diastolic blood pressure, respectively. Some of the ancestry-specific association signals were also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in the occurrence of ethnic differences in complex traits such as blood pressure.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-07T08:40:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002992","title":"Risk-adapted therapy for young children with medulloblastoma (SJYC07): results and molecular analysis from a multicenter phase II Trial","description":"**Background**\nYoung children with medulloblastoma have inferior survival to older children. While the principal difference is due to radiation-sparing therapy, radiation is not an absolute requisite for survival of all. We aimed to estimate the event-free survival of young medulloblastoma patients with a robust sample size using different treatment strategies designed to defer, reduce, or delay radiation exposure. These strategies were deemed reasonable at the start of the trial by physicians and ethics review board. Additionally, we aimed to define the molecular characteristics associated with progression-free survival.\n\n**Interpretation**\nThe risk-adapted approach failed to identify an acceptable benefit despite being well-tolerated. However, through the prespecified application of integrative genomics to this clinical trial cohort, we identified a good-responder SHH-subtype (iSHH-II) that exhibits excellent progression-free survival in the absence of radiation, intra-ventricular chemotherapy, or high-dose chemotherapy; a poorresponder SHH-subtype (iSHH-I); and very poor progression-free survival for G3/G4 medulloblastoma. These findings support the development of a molecularly-driven risk-adapted approach that will shape risk stratification and therapy on future medulloblastoma trials for young children.","abstract":"**Background**\nYoung children with medulloblastoma have inferior survival to older children. While the principal difference is due to radiation-sparing therapy, radiation is not an absolute requisite for survival of all. We aimed to estimate the event-free survival of young medulloblastoma patients with a robust sample size using different treatment strategies designed to defer, reduce, or delay radiation exposure. These strategies were deemed reasonable at the start of the trial by physicians and ethics review board. Additionally, we aimed to define the molecular characteristics associated with progression-free survival.\n\n**Interpretation**\nThe risk-adapted approach failed to identify an acceptable benefit despite being well-tolerated. However, through the prespecified application of integrative genomics to this clinical trial cohort, we identified a good-responder SHH-subtype (iSHH-II) that exhibits excellent progression-free survival in the absence of radiation, intra-ventricular chemotherapy, or high-dose chemotherapy; a poorresponder SHH-subtype (iSHH-I); and very poor progression-free survival for G3/G4 medulloblastoma. These findings support the development of a molecularly-driven risk-adapted approach that will shape risk stratification and therapy on future medulloblastoma trials for young children.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002993","title":"A benchmarking resource for NGS testing of cancer predisposition genes","description":"A benchmarking resource of 639 individuals, to assess the analytical sensitivity of cancer predisposition gene (CPG) testing.The dataset includes sequencing data generated using the TruSight Cancer Panel (TSCP) a targeted NGS assay for analysis of CPGs and orthogonally generated data supporting at least one pathogenic variant in a CPG for a total of 645 pathogenic CPG variants.The set of pathogenic CPG variants includes strong representation of some of the most challenging types of pathogenic variants, with 339 indels, including 16 complex indels and 24 insertions or deletions with length greater than 5bp, and 74 exon CNVs, including 23 single exon CNVs. There are 502 pathogenic variants in BRCA1 or BRCA2, making this an important first-line validation dataset for laboratories performing NGS testing of BRCA1 and BRCA2.","abstract":"A benchmarking resource of 639 individuals, to assess the analytical sensitivity of cancer predisposition gene (CPG) testing.The dataset includes sequencing data generated using the TruSight Cancer Panel (TSCP) a targeted NGS assay for analysis of CPGs and orthogonally generated data supporting at least one pathogenic variant in a CPG for a total of 645 pathogenic CPG variants.The set of pathogenic CPG variants includes strong representation of some of the most challenging types of pathogenic variants, with 339 indels, including 16 complex indels and 24 insertions or deletions with length greater than 5bp, and 74 exon CNVs, including 23 single exon CNVs. There are 502 pathogenic variants in BRCA1 or BRCA2, making this an important first-line validation dataset for laboratories performing NGS testing of BRCA1 and BRCA2.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-08T09:54:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002994","title":"FAM50_knockout_effect_on_chromatin","description":"Melanoma is the most lethal form of skin cancer, with a one year survival of stage IV disease of only fifty percent. S substantial proportion of patients fail to response to currently available treatments. Through a CRISPR dropout screen we have identified a number of synthetic lethal interactions within melanoma. One of these interactions is between two novel genes who's function is unknown. Through knockout of the pair of the genes we are interested in finding the mechanism by which the loss of both genes is lethal to the cell. Through performing ATACseq we hope to gain some insight into the role of these novel genes.","abstract":"Melanoma is the most lethal form of skin cancer, with a one year survival of stage IV disease of only fifty percent. S substantial proportion of patients fail to response to currently available treatments. Through a CRISPR dropout screen we have identified a number of synthetic lethal interactions within melanoma. One of these interactions is between two novel genes who's function is unknown. Through knockout of the pair of the genes we are interested in finding the mechanism by which the loss of both genes is lethal to the cell. Through performing ATACseq we hope to gain some insight into the role of these novel genes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002995","title":"Saif Test","description":"This is a test for Saif","abstract":"This is a test for Saif","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002996","title":"Host whole genome variations are associated with neurocognitive outcome in survivors of pediatric medulloblastoma","description":"Host whole genome analysis is a promising source of predictive information for long-term morbidity in cancer survivors. However, studies on genetic predictors of long-term outcome, particularly neurocognitive function following chemoradiation in pediatric oncology are limited. In the present study, we evaluated variations in host whole genome single nucleotide polymorphisms (SNPs) and their association with cognitive outcome. Whole-genome SNP analysis of host peripheral blood was conducted on 22 medulloblastoma long-term survivors, of whom 18 completed neuropsychological testing. First, unsupervised consensus clustering of the most variable SNPs within 409 genes involved in DNA repair was performed. Discrete variant groups were identified, although they were not associated with cognitive outcome, suggesting that variations in genes corresponding to a single functional group may be insufficient to predict long-term outcome alone. In support of this interpretation, unsupervised hierarchical clustering analysis using disease-associated gene variants by cognitive impairment status yielded two distinct variant clusters comprised of 36 variants, 34 of which were in noncoding regions. These findings illustrate for the first time that cognitively impaired survivors have a distinct variant profile compared to other medulloblastoma survivors. Future research in larger cohorts is needed to validate host genome predictors of cognitive impairment that may impact clinical management.","abstract":"Host whole genome analysis is a promising source of predictive information for long-term morbidity in cancer survivors. However, studies on genetic predictors of long-term outcome, particularly neurocognitive function following chemoradiation in pediatric oncology are limited. In the present study, we evaluated variations in host whole genome single nucleotide polymorphisms (SNPs) and their association with cognitive outcome. Whole-genome SNP analysis of host peripheral blood was conducted on 22 medulloblastoma long-term survivors, of whom 18 completed neuropsychological testing. First, unsupervised consensus clustering of the most variable SNPs within 409 genes involved in DNA repair was performed. Discrete variant groups were identified, although they were not associated with cognitive outcome, suggesting that variations in genes corresponding to a single functional group may be insufficient to predict long-term outcome alone. In support of this interpretation, unsupervised hierarchical clustering analysis using disease-associated gene variants by cognitive impairment status yielded two distinct variant clusters comprised of 36 variants, 34 of which were in noncoding regions. These findings illustrate for the first time that cognitively impaired survivors have a distinct variant profile compared to other medulloblastoma survivors. Future research in larger cohorts is needed to validate host genome predictors of cognitive impairment that may impact clinical management.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-10T15:24:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002997","title":"Histone acetylome-wide association study identifies epigenetic changes and a protective host response mechanism in tuberculosis","description":"Epigenetic mechanisms are thought to play an important role in the pathogenesis of infectious diseases. Here, we describe the first histone acetylome-wide association study (HAWAS) of an infectious disease, based on genome-wide H3K27 acetylation profiling of peripheral granulocytes and monocytes from subjects with active Mycobacterium tuberculosis (Mtb) infection and healthy controls (135 ChIP-seq datasets). In the Chinese discovery cohort, we detected &gt;2,000 differentially acetylated loci in either cell type. We observed concordant chromatin changes in a multi-ethnic validation cohort (Chinese, Malay, Indian), thus demonstrating that HAWAS can be independently corroborated. We also performed histone acetylation QTL analysis on the dataset and identified 5 candidate causal variants associated with susceptibility to Mycobacterium leprae. Our study demonstrates the reproducibility of HAWAS and provides a resource for investigating Mtb host response mechanisms and developing host-directed therapies.","abstract":"Epigenetic mechanisms are thought to play an important role in the pathogenesis of infectious diseases. Here, we describe the first histone acetylome-wide association study (HAWAS) of an infectious disease, based on genome-wide H3K27 acetylation profiling of peripheral granulocytes and monocytes from subjects with active Mycobacterium tuberculosis (Mtb) infection and healthy controls (135 ChIP-seq datasets). In the Chinese discovery cohort, we detected &gt;2,000 differentially acetylated loci in either cell type. We observed concordant chromatin changes in a multi-ethnic validation cohort (Chinese, Malay, Indian), thus demonstrating that HAWAS can be independently corroborated. We also performed histone acetylation QTL analysis on the dataset and identified 5 candidate causal variants associated with susceptibility to Mycobacterium leprae. Our study demonstrates the reproducibility of HAWAS and provides a resource for investigating Mtb host response mechanisms and developing host-directed therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001002998","title":"Integrated Genomic, Epigenetic, and Expression Analyses of Ovarian Cancer Cell Lines","description":"Epithelial ovarian carcinoma of all subtypes has one of the worst outcomes of any human cancer. To improve our understanding of underlying biology and therapeutic possibilities in this disease, we performed whole genome sequencing, methylation, and expression analyses of a comprehensive set of 47 ovarian cancer cell lines representing different histologic tumor subtypes. Given the challenges of genomic analyses in tumors without matched normal samples, we developed novel approaches for detection of somatic alterations and used these to identify sequence, copy number, and rearrangement changes and integrated these with genome-wide epigenetic and expression alterations. Ovarian cancer cell lines had molecular changes in genes involved in cell cycle, PI3K, RAS, BRCA, chromatin regulating, and p53 pathways, and displayed global mutation and methylation changes similar to primary ovarian carcinoma. We identified alterations not previously implicated in ovarian cancer including amplification or overexpression of ASXL1 and H3F3B, deletion or underexpression of CDC73 and members of the TGF beta receptor pathway, including TGFBR2, SMAD3 and SMAD4, in-frame rearrangements of YAP1-MAML2 and IKZF2-ERBB4, and fusions involving MET, NF1, FBXW7 and CCND1. Integrating cell line alterations with dose-response data using three targeted therapies revealed novel molecular dependencies, including increased sensitivity of tumors with PIK3CA and PPP2R1A alterations to PI3K inhibitor GNE-493, those with MYC amplifications to PARP inhibitor BMN673, and SMAD4 alterations to MEK inhibitor MEK162. Genome-wide analyses revealed intrachromosomal rearrangements as an improved measure of sensitivity to PARP inhibition compared to the homologous recombination defect (HRD) score. This study provides a comprehensive resource of molecular information for ovarian cancer cell line models and a pharmacogenomic platform for developing rational cancer therapeutic strategies.","abstract":"Epithelial ovarian carcinoma of all subtypes has one of the worst outcomes of any human cancer. To improve our understanding of underlying biology and therapeutic possibilities in this disease, we performed whole genome sequencing, methylation, and expression analyses of a comprehensive set of 47 ovarian cancer cell lines representing different histologic tumor subtypes. Given the challenges of genomic analyses in tumors without matched normal samples, we developed novel approaches for detection of somatic alterations and used these to identify sequence, copy number, and rearrangement changes and integrated these with genome-wide epigenetic and expression alterations. Ovarian cancer cell lines had molecular changes in genes involved in cell cycle, PI3K, RAS, BRCA, chromatin regulating, and p53 pathways, and displayed global mutation and methylation changes similar to primary ovarian carcinoma. We identified alterations not previously implicated in ovarian cancer including amplification or overexpression of ASXL1 and H3F3B, deletion or underexpression of CDC73 and members of the TGF beta receptor pathway, including TGFBR2, SMAD3 and SMAD4, in-frame rearrangements of YAP1-MAML2 and IKZF2-ERBB4, and fusions involving MET, NF1, FBXW7 and CCND1. Integrating cell line alterations with dose-response data using three targeted therapies revealed novel molecular dependencies, including increased sensitivity of tumors with PIK3CA and PPP2R1A alterations to PI3K inhibitor GNE-493, those with MYC amplifications to PARP inhibitor BMN673, and SMAD4 alterations to MEK inhibitor MEK162. Genome-wide analyses revealed intrachromosomal rearrangements as an improved measure of sensitivity to PARP inhibition compared to the homologous recombination defect (HRD) score. This study provides a comprehensive resource of molecular information for ovarian cancer cell line models and a pharmacogenomic platform for developing rational cancer therapeutic strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-14T15:14:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001002999","title":"Pheno-Seq, linking 3D phenotypes of clonal tumor spheroids to gene expression","description":"3D-culture systems have advanced cancer modeling by reflecting physiological characteristics of in-vivo tissues, but our understanding of functional intratumor heterogeneity including visual phenotypes and underlying gene expression is still limited. Transcriptional heterogeneity can be dissected by single-cell RNA-sequencing, but these technologies suffer from low RNA-input and fail to directly correlate gene expression with contextual cellular phenotypes. Here we present pheno-seq for integrated high-throughput imaging and transcriptomic profiling of clonal tumor spheroids derived from 3D models of breast and colorectal cancer. Specifically, we identify characteristic expression signatures that are associated with heterogeneous invasive and proliferative behavior including a rare cell subtype. Furthermore, we identify functionally relevant transcriptional regulators missed by single-cell RNA-seq, link visual phenotypes defined by heterogenous expression to inhibitor response and infer single-cell regulatory states by deconvolution. We anticipate that directly linking molecular features with patho-phenotypes of cancer cells will improve the understanding of intratumor heterogeneity and consequently prove to be useful for translational research.","abstract":"3D-culture systems have advanced cancer modeling by reflecting physiological characteristics of in-vivo tissues, but our understanding of functional intratumor heterogeneity including visual phenotypes and underlying gene expression is still limited. Transcriptional heterogeneity can be dissected by single-cell RNA-sequencing, but these technologies suffer from low RNA-input and fail to directly correlate gene expression with contextual cellular phenotypes. Here we present pheno-seq for integrated high-throughput imaging and transcriptomic profiling of clonal tumor spheroids derived from 3D models of breast and colorectal cancer. Specifically, we identify characteristic expression signatures that are associated with heterogeneous invasive and proliferative behavior including a rare cell subtype. Furthermore, we identify functionally relevant transcriptional regulators missed by single-cell RNA-seq, link visual phenotypes defined by heterogenous expression to inhibitor response and infer single-cell regulatory states by deconvolution. We anticipate that directly linking molecular features with patho-phenotypes of cancer cells will improve the understanding of intratumor heterogeneity and consequently prove to be useful for translational research.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-14T19:18:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003000","title":"Biallelic tumor suppressor loss and DNA repair defects in de novo small cell prostate cancer","description":"Small cell prostatic carcinoma (SCPC) is an aggressive pathology that is managed similar to small cell lung cancer. SCPC can evolve from prostatic adenocarcinoma in response to androgen deprivation therapy but in rare cases is present at initial cancer diagnosis. The molecular etiology of de novo SCPC is incompletely understood due to the scarcity of tumor tissue and the brief life expectancy of patients. Through a retrospective search of our regional oncology pharmacy database, we identified 18 patients diagnosed with de novo SCPC between 2004 and 2017. Ten patients had pure SCPC pathology and the remainder had some admixed adenocarcinoma foci, but all were treated with first line platinum-based chemotherapy. Median overall survival was 28 months. We performed targeted DNA sequencing, whole exome sequencing and mRNA profiling on formalin-fixed paraffin embedded archival tumor tissue. We observed frequent biallelic deletion and/or mutation of tumor suppressors TP53, RB1 and PTEN, similar to treatment-related SCPC. Indeed, at the RNA level pure de novo SCPC closely resembled treatment-related SCPC. However, five patients had biallelic loss of DNA repair genes including BRCA1, BRCA2, ATM and MSH2/6: potentially underlying the high genomic instability of this rare disease variant. Two patients with pure de novo SCPC harbored ETS gene rearrangements to androgen-driven promoters, consistent with evolution of de novo SCPC from an androgen-driven ancestor. Overall, our results reveal a highly aggressive molecular landscape underlies this unusual pathologic variant, and propose opportunities for targeted therapy strategies in a disease with few treatment options.","abstract":"Small cell prostatic carcinoma (SCPC) is an aggressive pathology that is managed similar to small cell lung cancer. SCPC can evolve from prostatic adenocarcinoma in response to androgen deprivation therapy but in rare cases is present at initial cancer diagnosis. The molecular etiology of de novo SCPC is incompletely understood due to the scarcity of tumor tissue and the brief life expectancy of patients. Through a retrospective search of our regional oncology pharmacy database, we identified 18 patients diagnosed with de novo SCPC between 2004 and 2017. Ten patients had pure SCPC pathology and the remainder had some admixed adenocarcinoma foci, but all were treated with first line platinum-based chemotherapy. Median overall survival was 28 months. We performed targeted DNA sequencing, whole exome sequencing and mRNA profiling on formalin-fixed paraffin embedded archival tumor tissue. We observed frequent biallelic deletion and/or mutation of tumor suppressors TP53, RB1 and PTEN, similar to treatment-related SCPC. Indeed, at the RNA level pure de novo SCPC closely resembled treatment-related SCPC. However, five patients had biallelic loss of DNA repair genes including BRCA1, BRCA2, ATM and MSH2/6: potentially underlying the high genomic instability of this rare disease variant. Two patients with pure de novo SCPC harbored ETS gene rearrangements to androgen-driven promoters, consistent with evolution of de novo SCPC from an androgen-driven ancestor. Overall, our results reveal a highly aggressive molecular landscape underlies this unusual pathologic variant, and propose opportunities for targeted therapy strategies in a disease with few treatment options.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003001","title":"Spatial Transcriptomics on prostate cancer heterogeneity","description":"Intratumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal prostate cancer using the spatial transcriptomics (ST) technology. Utilizing a novel approach for deconvolution, we analyze the transcriptomes of nearly 6750 tissue regions and extract distinct expression profiles for the different tissue components, such as stroma, normal and PIN glands, immune cells and cancer. We distinguish healthy and diseased areas and thereby provide insight into gene expression changes during the progression of prostate cancer. Compared to pathologist annotations, we delineate the extent of cancer foci more accurately, interestingly without link to histological changes. We identify gene expression gradients in stroma adjacent to tumor regions that allow for re-stratification of the tumor microenvironment. The establishment of these profiles is the first step towards an unbiased view of prostate cancer and can serve as a dictionary for future studies.","abstract":"Intratumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal prostate cancer using the spatial transcriptomics (ST) technology. Utilizing a novel approach for deconvolution, we analyze the transcriptomes of nearly 6750 tissue regions and extract distinct expression profiles for the different tissue components, such as stroma, normal and PIN glands, immune cells and cancer. We distinguish healthy and diseased areas and thereby provide insight into gene expression changes during the progression of prostate cancer. Compared to pathologist annotations, we delineate the extent of cancer foci more accurately, interestingly without link to histological changes. We identify gene expression gradients in stroma adjacent to tumor regions that allow for re-stratification of the tumor microenvironment. The establishment of these profiles is the first step towards an unbiased view of prostate cancer and can serve as a dictionary for future studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-15T10:32:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003002","title":"Next Generation Children project - WGS study of patients in NICU and PICU and their families","description":"With growing evidence that rare single gene disorders present in the neonatal period, there is a need for rapid, systematic, and comprehensive genomic diagnoses in ICUs to assist acute and long-term clinical decisions. This study aimed to identify genetic conditions in neonatal (NICU) and paediatric (PICU) intensive care populations. Whole genome sequencing data.","abstract":"With growing evidence that rare single gene disorders present in the neonatal period, there is a need for rapid, systematic, and comprehensive genomic diagnoses in ICUs to assist acute and long-term clinical decisions. This study aimed to identify genetic conditions in neonatal (NICU) and paediatric (PICU) intensive care populations. Whole genome sequencing data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-15T14:43:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003003","title":"Epigenetic profiling of colorectal cancer initiating cells (CC-ICs) to identify bivalently marked genes (H3K4me3 and H3K27me3 ChIP-seq), and investigation of changes in transcriptome following EZH2 inhibition using RNA-seq.","description":"Epigenetic regulation of transcription plays a crucial role in lineage commitment of embryonic stem cells. Promoters of key lineage-specific differentiation genes are found in a repressed bivalent state, having both activating H3K4me3 and repressive H3K27me3 histone marks, making them poised for transcription upon loss of H3K27me3 in response to environmental cues. Whether the tumour-initiating, self-renewing, cancer-initiating cells (C-ICs) have similar epigenetic regulatory mechanism that prevent lineage commitment is unknown. In order to investigate bivalently marked and repressed promoters, we used a patient-derived CC-IC enriched model to identify the changes in transcriptome following inhibition of EZH2, the H3K27 methyltransferase. We also performed ChIP-seq for H3K27me3 and H3K4me3 at baseline in order to identify repressed and bivalently marked promoters.","abstract":"Epigenetic regulation of transcription plays a crucial role in lineage commitment of embryonic stem cells. Promoters of key lineage-specific differentiation genes are found in a repressed bivalent state, having both activating H3K4me3 and repressive H3K27me3 histone marks, making them poised for transcription upon loss of H3K27me3 in response to environmental cues. Whether the tumour-initiating, self-renewing, cancer-initiating cells (C-ICs) have similar epigenetic regulatory mechanism that prevent lineage commitment is unknown. In order to investigate bivalently marked and repressed promoters, we used a patient-derived CC-IC enriched model to identify the changes in transcriptome following inhibition of EZH2, the H3K27 methyltransferase. We also performed ChIP-seq for H3K27me3 and H3K4me3 at baseline in order to identify repressed and bivalently marked promoters.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-15T17:53:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003004","title":"Genentech study of gallbladder cancer","description":"Genomic characterization of gallbladder cancer using Exome-Seq, RNA-Seq and low pass whole genome sequencing.","abstract":"Genomic characterization of gallbladder cancer using Exome-Seq, RNA-Seq and low pass whole genome sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-16T18:08:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003005","title":"Lymphocyte_scRNA_seq","description":"As we age, our cells accumulate mutations, termed \"somatic mutations\". Somatic mutations, which exist in mosaic form throughout the body, are a direct record of the evolution of our cells. Some of these mutations are subject to neutral evolution. The study of neutral mutations can reveal the cell lineages resulting from normal development and tissue maintenance, and help us understand key demographic parameter of somatic evolution, such as population size and migration. Other mutations are under selection, resulting in the expansion or contraction of lineages. These mutations can lead to disease, such as cancer; however, the extent of selection on somatic mutations in not understood. We aim to understand the somatic evolution of the primary cells of the adaptive immune system, lymphocytes. As we age, lymphocytes accumulate somatic mutations, which reveal the evolutionary history of lymphocytes, as well as providing information about the particular mutations and lineage structures that contribute to age-related immune disorder. In order to understand somatic evolution in lymphocytes, we sequence lymphocytes from normal, healthy individuals across a range of ages. We perform whole-genome sequencing of single-cell derived T and B cell colonies to identify somatic mutations, and perform targeted deep-sequencing of these mutations. The lineages of T and B cells, and the frequencies of these mutations reveals the neutral and non-neutral evolutionary processes underlying lymphocyte growth.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"As we age, our cells accumulate mutations, termed \"somatic mutations\". Somatic mutations, which exist in mosaic form throughout the body, are a direct record of the evolution of our cells. Some of these mutations are subject to neutral evolution. The study of neutral mutations can reveal the cell lineages resulting from normal development and tissue maintenance, and help us understand key demographic parameter of somatic evolution, such as population size and migration. Other mutations are under selection, resulting in the expansion or contraction of lineages. These mutations can lead to disease, such as cancer; however, the extent of selection on somatic mutations in not understood. We aim to understand the somatic evolution of the primary cells of the adaptive immune system, lymphocytes. As we age, lymphocytes accumulate somatic mutations, which reveal the evolutionary history of lymphocytes, as well as providing information about the particular mutations and lineage structures that contribute to age-related immune disorder. In order to understand somatic evolution in lymphocytes, we sequence lymphocytes from normal, healthy individuals across a range of ages. We perform whole-genome sequencing of single-cell derived T and B cell colonies to identify somatic mutations, and perform targeted deep-sequencing of these mutations. The lineages of T and B cells, and the frequencies of these mutations reveals the neutral and non-neutral evolutionary processes underlying lymphocyte growth.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003006","title":"Genomic profiling of paediatric glioma cell lines","description":"Although paediatric gliomas resemble their adult counterparts in many ways, there appear to be distinct clinical and biological differences. One important factor hampering the development of new targeted therapies is the relative lack of cell lines derived from childhood glioma patients, as it is unclear whether the well-established adult lines commonly used are representative of the underlying molecular genetics of childhood tumours. We have carried out a detailed molecular profiling of paediatric glioma cell lines KNS42, SF188, UW479, RES259 and RES186.","abstract":"Although paediatric gliomas resemble their adult counterparts in many ways, there appear to be distinct clinical and biological differences. One important factor hampering the development of new targeted therapies is the relative lack of cell lines derived from childhood glioma patients, as it is unclear whether the well-established adult lines commonly used are representative of the underlying molecular genetics of childhood tumours. We have carried out a detailed molecular profiling of paediatric glioma cell lines KNS42, SF188, UW479, RES259 and RES186.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-17T13:25:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003007","title":"Biallelic tumor suppressor loss and DNA repair defects in de novo small cell prostate cancer","description":"Small cell prostatic carcinoma (SCPC) is an aggressive pathology that is managed similar to small cell lung cancer. SCPC can evolve from prostatic adenocarcinoma in response to androgen deprivation therapy but in rare cases is present at initial cancer diagnosis. The molecular etiology of de novo SCPC is incompletely understood due to the scarcity of tumor tissue and the brief life expectancy of patients. Through a retrospective search of our regional oncology pharmacy database, we identified 18 patients diagnosed with de novo SCPC between 2004 and 2017. Ten patients had pure SCPC pathology and the remainder had some admixed adenocarcinoma foci, but all were treated with first line platinum-based chemotherapy. Median overall survival was 28 months. We performed targeted DNA sequencing, whole exome sequencing and mRNA profiling on formalin-fixed paraffin embedded archival tumor tissue. We observed frequent biallelic deletion and/or mutation of tumor suppressors TP53, RB1 and PTEN, similar to treatment related SCPC. Indeed, at the RNA level pure de novo SCPC closely resembled treatment-related SCPC. However, five patients had biallelic loss of DNA repair genes including BRCA1, BRCA2, ATM and MSH2/6: potentially underlying the high genomic instability of this rare disease variant. Two patients with pure de novo SCPC harbored ETS gene rearrangements to androgen-driven promoters, consistent with evolution of de novo SCPC from an androgen-driven ancestor. Overall, our results reveal a highly aggressive molecular landscape underlies this unusual pathologic variant, and propose opportunities for targeted therapy strategies in a disease with few treatment options.","abstract":"Small cell prostatic carcinoma (SCPC) is an aggressive pathology that is managed similar to small cell lung cancer. SCPC can evolve from prostatic adenocarcinoma in response to androgen deprivation therapy but in rare cases is present at initial cancer diagnosis. The molecular etiology of de novo SCPC is incompletely understood due to the scarcity of tumor tissue and the brief life expectancy of patients. Through a retrospective search of our regional oncology pharmacy database, we identified 18 patients diagnosed with de novo SCPC between 2004 and 2017. Ten patients had pure SCPC pathology and the remainder had some admixed adenocarcinoma foci, but all were treated with first line platinum-based chemotherapy. Median overall survival was 28 months. We performed targeted DNA sequencing, whole exome sequencing and mRNA profiling on formalin-fixed paraffin embedded archival tumor tissue. We observed frequent biallelic deletion and/or mutation of tumor suppressors TP53, RB1 and PTEN, similar to treatment related SCPC. Indeed, at the RNA level pure de novo SCPC closely resembled treatment-related SCPC. However, five patients had biallelic loss of DNA repair genes including BRCA1, BRCA2, ATM and MSH2/6: potentially underlying the high genomic instability of this rare disease variant. Two patients with pure de novo SCPC harbored ETS gene rearrangements to androgen-driven promoters, consistent with evolution of de novo SCPC from an androgen-driven ancestor. Overall, our results reveal a highly aggressive molecular landscape underlies this unusual pathologic variant, and propose opportunities for targeted therapy strategies in a disease with few treatment options.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-17T19:53:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003008","title":"Age-related remodeling of apparently normal esophageal epithelia by common cancer drivers","description":"Driver mutated clones multi-focally emerged from early adulthood and over years, increase their number and size, ultimately remodeling the entire esophageal epithelia in extreme elderly.  Our results suggest that clonal expansion in esophageal epithelia is an inevitable consequence of normal aging, differentially impacting the development of cancer depending on mutation type and exposure to drinking and smoking.","abstract":"Driver mutated clones multi-focally emerged from early adulthood and over years, increase their number and size, ultimately remodeling the entire esophageal epithelia in extreme elderly.  Our results suggest that clonal expansion in esophageal epithelia is an inevitable consequence of normal aging, differentially impacting the development of cancer depending on mutation type and exposure to drinking and smoking.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-18T05:58:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003009","title":"SNP array of paired cancer/normal epithelial samples from 31 ESCC patients","description":"Driver mutated clones multi-focally emerged from early adulthood and over years, increase their number and size, ultimately remodeling the entire esophageal epithelia in extreme elderly.  Our results suggest that clonal expansion in esophageal epithelia is an inevitable consequence of normal aging, differentially impacting the development of cancer depending on mutation type and exposure to drinking and smoking.","abstract":"Driver mutated clones multi-focally emerged from early adulthood and over years, increase their number and size, ultimately remodeling the entire esophageal epithelia in extreme elderly.  Our results suggest that clonal expansion in esophageal epithelia is an inevitable consequence of normal aging, differentially impacting the development of cancer depending on mutation type and exposure to drinking and smoking.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003010","title":"CTCF/cohesin-binding sites are frequently mutated in cancer","description":"Cohesin is present in almost all active enhancer regions, where it is associated with transcription factors. Cohesin frequently colocalizes with CTCF (CCCTC-binding factor), affecting genomic stability, expression and epigenetic homeostasis. Cohesin subunits are mutated in cancer, but CTCF/cohesin-binding sites (CBSs) in DNA have not been examined for mutations. Here we report frequent mutations at CBSs in cancers displaying a mutational signature where mutations in A•T base pairs predominate. Integration of whole-genome sequencing data from 213 colorectal cancer (CRC) samples and chromatin immunoprecipitation sequencing (ChIP-exo) data identified frequent point mutations at CBSs. In contrast, CRCs showing an ultramutator phenotype caused by defects in the exonuclease domain of DNA polymerase ɛ (POLE) displayed significantly fewer mutations at and adjacent to CBSs. Analysis of public data showed that multiple cancer types accumulate CBS mutations. CBSs are a major mutational hotspot in the noncoding cancer genome.","abstract":"Cohesin is present in almost all active enhancer regions, where it is associated with transcription factors. Cohesin frequently colocalizes with CTCF (CCCTC-binding factor), affecting genomic stability, expression and epigenetic homeostasis. Cohesin subunits are mutated in cancer, but CTCF/cohesin-binding sites (CBSs) in DNA have not been examined for mutations. Here we report frequent mutations at CBSs in cancers displaying a mutational signature where mutations in A•T base pairs predominate. Integration of whole-genome sequencing data from 213 colorectal cancer (CRC) samples and chromatin immunoprecipitation sequencing (ChIP-exo) data identified frequent point mutations at CBSs. In contrast, CRCs showing an ultramutator phenotype caused by defects in the exonuclease domain of DNA polymerase ɛ (POLE) displayed significantly fewer mutations at and adjacent to CBSs. Analysis of public data showed that multiple cancer types accumulate CBS mutations. CBSs are a major mutational hotspot in the noncoding cancer genome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-18T08:30:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003011","title":"Indonesian Genome Diversity Project","description":"Indonesia, the world’s fourth largest country by population, comprises an archipelago of about 900 permanently inhabited islands in tropical Asia, and hosts an astonishing array of human diversity that remains largely underrepresented in modern biological surveys. The region is unique for its key role in both the early and recent evolution of Homo outside of Africa. It has one of the first traces of anatomically modern humans in Eurasia, and was the focus of extensive interaction between archaic hominins and humans – both in the likely co-existence of H. floresiensis with modern humans, and in the introgression of Denisovans into the ancestors of its present inhabitants. More recently, Indonesia was a center of the spread of Neolithic culture by Austronesian speakers. Advancing maritime technologies allowed farming populations to treat this region as a springboard to reach oceanic islands as remote as Madagascar, Hawaii, Easter Island and New Zealand. Here we present complete human genomes from healthy individuals from multiple key islands in Indonesia and Papua. The genomes were sequenced to high depth (30x). The purpose of this dataset is to address different questions of human evolution in Island Southeast Asia and beyond, including early settlement of the area by anatomically modern humans, population structure, genetic admixture and adaptation, and contacts with archaic hominins. We employed a sampling strategy to capture a broad range of diversity across the region incorporating an average of 12 samples from each of 14 islands spanning Indonesia and Papua, from Sumatra in the west to New Britain in the east. Genomes from this dataset form part of an ongoing project to describe and understand human evolutionary history in Island Southeast Asia and Eurasia in general.","abstract":"Indonesia, the world’s fourth largest country by population, comprises an archipelago of about 900 permanently inhabited islands in tropical Asia, and hosts an astonishing array of human diversity that remains largely underrepresented in modern biological surveys. The region is unique for its key role in both the early and recent evolution of Homo outside of Africa. It has one of the first traces of anatomically modern humans in Eurasia, and was the focus of extensive interaction between archaic hominins and humans – both in the likely co-existence of H. floresiensis with modern humans, and in the introgression of Denisovans into the ancestors of its present inhabitants. More recently, Indonesia was a center of the spread of Neolithic culture by Austronesian speakers. Advancing maritime technologies allowed farming populations to treat this region as a springboard to reach oceanic islands as remote as Madagascar, Hawaii, Easter Island and New Zealand. Here we present complete human genomes from healthy individuals from multiple key islands in Indonesia and Papua. The genomes were sequenced to high depth (30x). The purpose of this dataset is to address different questions of human evolution in Island Southeast Asia and beyond, including early settlement of the area by anatomically modern humans, population structure, genetic admixture and adaptation, and contacts with archaic hominins. We employed a sampling strategy to capture a broad range of diversity across the region incorporating an average of 12 samples from each of 14 islands spanning Indonesia and Papua, from Sumatra in the west to New Britain in the east. Genomes from this dataset form part of an ongoing project to describe and understand human evolutionary history in Island Southeast Asia and Eurasia in general.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003012","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___GI___WGS","description":"The aim of this project is to investiagte somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the studyof normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to idnetifiy and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","abstract":"The aim of this project is to investiagte somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the studyof normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to idnetifiy and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-18T15:56:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003013","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___GI___TGS","description":"Somatic mutations (driver mutations) and clonal dynamics in normal human tissues from the gastrointestinal tract.","abstract":"The aim of this project is to investiagte somatic mutations and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the study of normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to idnetifiy and isolate specific cell populations which are then subjected to targeted genome seqeuncing to describe driver mutation frequency and clonal expansions in normal tissues.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003014","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___BD___WGS","description":"The aim of this project is to investiagte somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the biliary tree. The project will involve the studyof normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to idnetifiy and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","abstract":"The aim of this project is to investiagte somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the biliary tree. The project will involve the studyof normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to idnetifiy and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-18T14:05:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003015","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___BD___TGS","description":"Somatic mutations (driver mutations) and clonal dynamics in normal human tissues from the biliary tree.","abstract":"The aim of this project is to investiagte somatic mutations and clonal dynamics in normal (non-cancerous) human tissues from the biliary tree. The project will involve the study of normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to identify and isolate specific cell populations which are then subjected to targeted genome seqeuncing to describe driver mutation frequency and look for the presence of clonal expansions.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-18T14:07:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003016","title":"H3Africa - Identification and characterization of novel hereditary neurological disease genes in Mali.","description":"Despite the vast diversity of its populations, genetic studies in Africa have been limited. African populations, Malians in particular, have a high rate of intra-ethnic and consanguineous marriage, resulting in increased prevalence of autosomal recessive diseases. Family-based genetic studies can be limited in developed countries due to small sibships. The average fertility rate in Mali is over 6 births per woman, offering a unique opportunity to find new disease genes or mutations that can then be studied in other populations. Hereditary neurological diseases are very debilitating diseases, and developing countries, particularly in Africa, pay a high price in terms of disability-adjusted life years. Although most are currently untreatable, increasing awareness about hereditary neurological disorders can reduce this burden. This study will help to identify and characterize novel hereditary neurological disease genes in Mali. These genes are likely to be important in the normal function of the nervous system and to have important pathophysiological implications for African and other populations. This study will also train physicians and students in the characterization of neurodegenerative diseases as well as in genetic technology and molecular biology, and build a suitable research environment that will retain them.","abstract":"Despite the vast diversity of its populations, genetic studies in Africa have been limited. African populations, Malians in particular, have a high rate of intra-ethnic and consanguineous marriage, resulting in increased prevalence of autosomal recessive diseases. Family-based genetic studies can be limited in developed countries due to small sibships. The average fertility rate in Mali is over 6 births per woman, offering a unique opportunity to find new disease genes or mutations that can then be studied in other populations. Hereditary neurological diseases are very debilitating diseases, and developing countries, particularly in Africa, pay a high price in terms of disability-adjusted life years. Although most are currently untreatable, increasing awareness about hereditary neurological disorders can reduce this burden. This study will help to identify and characterize novel hereditary neurological disease genes in Mali. These genes are likely to be important in the normal function of the nervous system and to have important pathophysiological implications for African and other populations. This study will also train physicians and students in the characterization of neurodegenerative diseases as well as in genetic technology and molecular biology, and build a suitable research environment that will retain them.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-21T11:49:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003017","title":"Celiac disease-specific intestinal T cells analyzed with HLA-class II tetramers, RNA-seq and mass cytometry have a narrow, autoimmune-associated phenotype","description":"Celiac disease (CD) is an HLA-DQ2/8-associated autoimmune enteropathy driven by activation of gluten-specific CD4+ T lymphocytes upon gluten consumption. Much less is known about the phenotype and function of these cells or their correlation, if any, to disease-relevant cells in other autoimmune disorders. Here we use mass cytometry and RNA seq to show that gluten-specific blood and gut T cells occupy a small and phenotypically distinct T-cell subset.","abstract":"Celiac disease (CD) is an HLA-DQ2/8-associated autoimmune enteropathy driven by activation of gluten-specific CD4+ T lymphocytes upon gluten consumption. Much less is known about the phenotype and function of these cells or their correlation, if any, to disease-relevant cells in other autoimmune disorders. Here we use mass cytometry and RNA seq to show that gluten-specific blood and gut T cells occupy a small and phenotypically distinct T-cell subset.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-22T09:46:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003018","title":"GCAT | Genomes for life:  cohort study of the genomes of Catalonia","description":"The GCAT Study have recruited 20 000 participants aged 40–65 years. Participants who agreed to take part in the study completed a self-administered computer-driven questionnaire, and underwent blood pressure, cardiac frequency and anthropometry measurements. For each participant, blood plasma, blood serum and white blood cells are collected at baseline. \n\nA total of 5459  genomic profiles have been characterised by comprehensive genotyping. Genome-wide genotypes have been generated using Illumina Infinium SNP-bead array technology. We chose the Multi-Ethnic Global (MEGAEX, V.2) consortium array, a multipurpose, multiethnic  genotyping array with two million selected markers (including previously described germline mutations, insertions-deletions (InDels) and SNPs).We have strictly followed the standard manufacturer recommended automated protocol for the Infinium HTS Assay scanned with a HiScan confocal scanner (Illumina, San Diego, California, USA). Genome Studio V.2011.1 has been used for raw data analysis. Genotyping was performed at the Genomics and Bioinformatics Unit of the PMPPC Institute for Health Science Research Germans Trias i Pujol, in Badalona, Spain.\n\nFuture plans The first follow-up study started in December 2017 and will end by March 2018. Residences of all subjects will be geocoded during the following year. Several genomic analyses are ongoing, and metabolomic and genomic integrations will be performed to identify underlying genetic variants, as well as environmental factors that influence metabolites.\n\nhttp://dx.doi.org/10.1136/bmjopen-2017-018324","abstract":"The GCAT Study have recruited 20 000 participants aged 40–65 years. Participants who agreed to take part in the study completed a self-administered computer-driven questionnaire, and underwent blood pressure, cardiac frequency and anthropometry measurements. For each participant, blood plasma, blood serum and white blood cells are collected at baseline. \n\nA total of 5459  genomic profiles have been characterised by comprehensive genotyping. Genome-wide genotypes have been generated using Illumina Infinium SNP-bead array technology. We chose the Multi-Ethnic Global (MEGAEX, V.2) consortium array, a multipurpose, multiethnic  genotyping array with two million selected markers (including previously described germline mutations, insertions-deletions (InDels) and SNPs).We have strictly followed the standard manufacturer recommended automated protocol for the Infinium HTS Assay scanned with a HiScan confocal scanner (Illumina, San Diego, California, USA). Genome Studio V.2011.1 has been used for raw data analysis. Genotyping was performed at the Genomics and Bioinformatics Unit of the PMPPC Institute for Health Science Research Germans Trias i Pujol, in Badalona, Spain.\n\nFuture plans The first follow-up study started in December 2017 and will end by March 2018. Residences of all subjects will be geocoded during the following year. Several genomic analyses are ongoing, and metabolomic and genomic integrations will be performed to identify underlying genetic variants, as well as environmental factors that influence metabolites.\n\nhttp://dx.doi.org/10.1136/bmjopen-2017-018324","study_type":"Other","pubmed_ids":[29593016],"external_links":null,"is_released":true,"released_date":"2018-05-22T11:36:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003019","title":"German early-onset prostate cancer cohort of the Pan-Prostate Cancer Genome (PPCG) project DEPRECATED","description":"Prostate cancer is the most frequent malignant tumor in males and the second most frequent cause of cancer-related death. Currently, in Germany, more than 60,000 prostate cancers are diagnosed every year. Although most of these patients are treated in a curative attempt, more than 10,000 German men die from prostate cancer annually. Owing to the demographic changes of our society, a further doubling of prostate cancer incidences during the next 20 years is expected. Prostate cancer is generally considered a tumor of elderly men. However, a fraction of prostate cancers are diagnosed at the age of 55 years or less. For several reasons, these “early onset prostate cancers” may represent a key entity for the understanding of prostate cancer biology.First, it is likely that early onset prostate cancers represent a distinct molecular subgroup of prostate cancer (PCa), potentially characterized by relatively small numbers of genetic changes, some of which may be particularly strong driver mutations for PCa development. Second, a fraction of prostate cancers in young individuals could represent classical prostate cancers that are detected at a very early stage and might therefore have accumulated molecular changes/mutations occurring that are most instrumental for prostate cancer early detection. Third, PCa with hereditary backgrounds are likely to accumulate in the age group below 55 years. A comparison with other sample sets (e.g. from other ICGC consortia), a systematic genomic analysis of young men with PCa could therefore lead to the detection of mechanisms for hereditary PCa. Fourth, a better understanding of these tumors is particularly relevant as finding optimal treatment regimens is most critical in young cancer patients.We are analyzing the entire genomic DNA sequences of at least 200 PCas (and matched non-tumorous DNA) of young men (≤ 55y), to at least 30 fold coverage, and integrate single-nucleotide variants and genomic structural variations with differential methylation, mRNA and miRNA expression data.Tissues were collected at the University Medical Center Hamburg-Eppendorf. Sequencing was performed at DKFZ and NCT (Heidelberg), EMBL (Heidelberg), and MPIMG (Berlin). Data management and bioinformatic data analyses is being conducted at DKFZ.","abstract":"Prostate cancer is the most frequent malignant tumor in males and the second most frequent cause of cancer-related death. Currently, in Germany, more than 60,000 prostate cancers are diagnosed every year. Although most of these patients are treated in a curative attempt, more than 10,000 German men die from prostate cancer annually. Owing to the demographic changes of our society, a further doubling of prostate cancer incidences during the next 20 years is expected. Prostate cancer is generally considered a tumor of elderly men. However, a fraction of prostate cancers are diagnosed at the age of 55 years or less. For several reasons, these “early onset prostate cancers” may represent a key entity for the understanding of prostate cancer biology.First, it is likely that early onset prostate cancers represent a distinct molecular subgroup of prostate cancer (PCa), potentially characterized by relatively small numbers of genetic changes, some of which may be particularly strong driver mutations for PCa development. Second, a fraction of prostate cancers in young individuals could represent classical prostate cancers that are detected at a very early stage and might therefore have accumulated molecular changes/mutations occurring that are most instrumental for prostate cancer early detection. Third, PCa with hereditary backgrounds are likely to accumulate in the age group below 55 years. A comparison with other sample sets (e.g. from other ICGC consortia), a systematic genomic analysis of young men with PCa could therefore lead to the detection of mechanisms for hereditary PCa. Fourth, a better understanding of these tumors is particularly relevant as finding optimal treatment regimens is most critical in young cancer patients.We are analyzing the entire genomic DNA sequences of at least 200 PCas (and matched non-tumorous DNA) of young men (≤ 55y), to at least 30 fold coverage, and integrate single-nucleotide variants and genomic structural variations with differential methylation, mRNA and miRNA expression data.Tissues were collected at the University Medical Center Hamburg-Eppendorf. Sequencing was performed at DKFZ and NCT (Heidelberg), EMBL (Heidelberg), and MPIMG (Berlin). Data management and bioinformatic data analyses is being conducted at DKFZ.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003020","title":"EarlyEmbryo","description":"Aim of this study is to build a single-cell resolution map of early embryo development.Cells are processed in University of Cambridge, and converted to single-cell 10x library and sequenced in Sanger.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The aim of this study is to build a single-cell resolution map of human fetal cell development.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003021","title":"Somatic_mutation_and_clonal_evolution_in_the_human_testes","description":"In this study we aim to characterise the landscape of Pathogenic variants and clonal dynamics in normal and cancerous testes and their role in cancer predisposition. The study combines targeted sequencing and whole-genome sequencing of microbiopsies from testes. The range of patients studied will include healthy individuals, and patients with testicular cancer.","abstract":"In this study we aim to determine the clonal dynamics of spermatogenesis in adult testes and identify factors such as age that affect clonal dynamics.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-23T09:05:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003022","title":"Somatic_mutation_and_clonal_evolution_in_the_human_testes___TGS","description":"In this study we aim to characterise the landscape of Pathogenic variants and clonal dynamics in normal and cancerous testes and their role in cancer predisposition. The study combines targeted sequencing and whole-genome sequencing of microbiopsies from testes. The range of patients studied will include healthy individuals, and patients with testicular cancer.","abstract":"In this study we aim to determine the clonal dynamics of spermatogenesis in adult testes and identify factors such as age that affect clonal dynamics.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003023","title":"Somatic_mutation_and_clonal_evolution_in_the_human_testes___WES","description":"In this study we aim to characterise the landscape of Pathogenic variants and clonal dynamics in normal and cancerous testes and their role in cancer predisposition. The study combines targeted sequencing and whole-genome sequencing of microbiopsies from testes. The range of patients studied will include healthy individuals, and patients with testicular cancer.","abstract":"In this study we aim to determine the clonal dynamics of spermatogenesis in adult testes and identify factors such as age that affect clonal dynamics.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-23T09:17:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003024","title":"TET2_Clonal_Haematopoiesis","description":"Investigation of mutant TET-driven clonal haematopoiesis.","abstract":"A single-cell RNA sequencing study of CD34+ haematopoietic stem cells isolated from the bone marrow of a patient with a substantial mutant TET2 clone.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003025","title":"WGS/RNA-seq pair of an inflammatory hepatocellular adenoma (IHCA)","description":"A 49 years old female patient consulted for diarrhea, rectal bleeding and lower limbs edema and was diagnosed with systemic AA amyloidosis.\nAn inflammatory hepatocellular adenoma was further identified and resected, resulting in the improvement of amyloidosis-related symptoms. Molecular analyses of the tumor tissue revealed a somatic chromosome rearrangement responsible for interleukin-6 mRNA stabilization leading to an inflammatory acute response with serum amyloid A protein production by both neoplastic and normal hepatocytes.","abstract":"A 49 years old female patient consulted for diarrhea, rectal bleeding and lower limbs edema and was diagnosed with systemic AA amyloidosis.\nAn inflammatory hepatocellular adenoma was further identified and resected, resulting in the improvement of amyloidosis-related symptoms. Molecular analyses of the tumor tissue revealed a somatic chromosome rearrangement responsible for interleukin-6 mRNA stabilization leading to an inflammatory acute response with serum amyloid A protein production by both neoplastic and normal hepatocytes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-24T16:43:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003026","title":"Mutational Signature and Transcriptomic Classification Analyses as the Decisive Diagnostic Tools for a Cancer of Unknown Primary with Neuroendocrine Differentiation","description":"PURPOSE: Cancer of unknown primary (CUP) is a group of metastatic tumors in which the standard diagnostic work-up fails to identify the site of origin of the tumor. The potential impact of precision oncology on this group of patients is large since their tumors might have actionable driver mutations that can provide treatment options otherwise not available for patients with these fatal cancers. This study investigated if comprehensive genomics analyses could inform on the origin of the tumor. \nPATIENT AND METHODS: Here we describe a patient whose tumor was misdiagnosed at least three times. Next-generation sequencing, a PDX mouse model and bioinformatics was used to identify an actionable mutation, predict resistance development to the targeted therapy, and to correctly diagnose the origin of the tumor. The Cancer Genome Atlas was used to benchmark the bioinformatics workflow. \nRESULTS: Despite the lack of a known primary tumor site and the absence of diagnostic immunohistochemical markers, the origin of the patient's tumor was established using the novel bioinformatics workflow. This included a mutational signature analysis of the sequenced metastases and comparison of their transcriptomic profiles to a pan-cancer panel of tumors from The Cancer Genome Atlas. We further discuss the strengths and limitations of the latter approaches in the context of three potentially incorrectly diagnosed TCGA lung tumors. \nCONCLUSION: Comprehensive genomics analyses could inform on the origin of tumors in patients suffering from CUP.","abstract":"PURPOSE: Cancer of unknown primary (CUP) is a group of metastatic tumors in which the standard diagnostic work-up fails to identify the site of origin of the tumor. The potential impact of precision oncology on this group of patients is large since their tumors might have actionable driver mutations that can provide treatment options otherwise not available for patients with these fatal cancers. This study investigated if comprehensive genomics analyses could inform on the origin of the tumor. \nPATIENT AND METHODS: Here we describe a patient whose tumor was misdiagnosed at least three times. Next-generation sequencing, a PDX mouse model and bioinformatics was used to identify an actionable mutation, predict resistance development to the targeted therapy, and to correctly diagnose the origin of the tumor. The Cancer Genome Atlas was used to benchmark the bioinformatics workflow. \nRESULTS: Despite the lack of a known primary tumor site and the absence of diagnostic immunohistochemical markers, the origin of the patient's tumor was established using the novel bioinformatics workflow. This included a mutational signature analysis of the sequenced metastases and comparison of their transcriptomic profiles to a pan-cancer panel of tumors from The Cancer Genome Atlas. We further discuss the strengths and limitations of the latter approaches in the context of three potentially incorrectly diagnosed TCGA lung tumors. \nCONCLUSION: Comprehensive genomics analyses could inform on the origin of tumors in patients suffering from CUP.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-25T10:23:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003027","title":"Allele Balance Bias Identifies Systematic Genotyping Errors and False Disease Associations","description":"In recent years, Next Generation Sequencing (NGS) has become a cornerstone of clinical genetics and diagnostics. Many clinical applications require high precision, especially if rare events such as somatic mutations in cancer or genetic variants causing rare diseases need to be identified. Although random sequencing errors can be modeled statistically and deep sequencing minimizes their impact, systematic errors remain a problem even at high depth of coverage. Understanding their source is crucial to increase precision of clinical NGS applications. In this work, we studied the relation between recurrent biases in allele balance (AB), systematic errors and false positive variant calls across a large cohort of human samples analyzed by whole exome sequencing (WES). We have modeled the allele balance distribution for biallelic genotypes in 987 WES samples in order to identify positions recurrently deviating significantly from the expectation, a phenomenon we termed allele balance bias (ABB). Furthermore, we have developed a genotype callability score based on ABB for all positions of the human exome, which detects false positive variant calls that passed state-of-the-art filters. Finally, we demonstrate the use of ABB for detection of false associations proposed by rare variant association studies (RVAS).","abstract":"In recent years, Next Generation Sequencing (NGS) has become a cornerstone of clinical genetics and diagnostics. Many clinical applications require high precision, especially if rare events such as somatic mutations in cancer or genetic variants causing rare diseases need to be identified. Although random sequencing errors can be modeled statistically and deep sequencing minimizes their impact, systematic errors remain a problem even at high depth of coverage. Understanding their source is crucial to increase precision of clinical NGS applications. In this work, we studied the relation between recurrent biases in allele balance (AB), systematic errors and false positive variant calls across a large cohort of human samples analyzed by whole exome sequencing (WES). We have modeled the allele balance distribution for biallelic genotypes in 987 WES samples in order to identify positions recurrently deviating significantly from the expectation, a phenomenon we termed allele balance bias (ABB). Furthermore, we have developed a genotype callability score based on ABB for all positions of the human exome, which detects false positive variant calls that passed state-of-the-art filters. Finally, we demonstrate the use of ABB for detection of false associations proposed by rare variant association studies (RVAS).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-25T14:06:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003028","title":"The evolutionary history of human colitis-associated colorectal cancer","description":"Inflammatory bowel disease confers an increased lifetime risk of developing colorectal cancer (CRC), and colitis-associated CRC (CA-CRC) is molecularly distinct from sporadic CRC (S-CRC). Here we have dissected the evolutionary history of CA-CRC using multi-region sequencing.\n\nExome sequencing was performed on fresh-frozen multiple regions of carcinoma, adjacent non-cancerous mucosa and blood from 12 CA-CRC patients (n=55 exomes), and key variants were validated with orthogonal methods. Genome-wide copy number profiling was performed using SNP arrays and low-pass whole genome sequencing on archival non-dysplastic mucosa (n=9), low-grade dysplasia (LGD, n=30), high-grade dysplasia (HGD, n=13), mixed LGD/HGD (n=7) and CA-CRC (n=19). Phylogenetic trees were reconstructed, and evolutionary analysis used to reveal the temporal sequence of events leading to CA-CRC.\n\n10/12 tumors were microsatellite stable with a median mutation burden of 3.0 single nucleotide alterations (SNAs) per Mb, around 20% higher than S-CRC (2.5 SNAs/Mb), and consistent with elevated aging-associated mutational processes. Non-dysplastic mucosa had considerable mutation burden (median 47 SNAs), including mutations shared with the neighboring CA-CRC, indicating a pre-cancer mutational field. CA-CRCs were often near-triploid (42%) or near-tetraploid (21%) and phylogenetic analysis revealed that copy number alterations (CNAs) began to accrue in non-dysplastic bowel, but the LGD/HGD transition often involved a punctuated catastrophic CNA increase.","abstract":"Inflammatory bowel disease confers an increased lifetime risk of developing colorectal cancer (CRC), and colitis-associated CRC (CA-CRC) is molecularly distinct from sporadic CRC (S-CRC). Here we have dissected the evolutionary history of CA-CRC using multi-region sequencing.\n\nExome sequencing was performed on fresh-frozen multiple regions of carcinoma, adjacent non-cancerous mucosa and blood from 12 CA-CRC patients (n=55 exomes), and key variants were validated with orthogonal methods. Genome-wide copy number profiling was performed using SNP arrays and low-pass whole genome sequencing on archival non-dysplastic mucosa (n=9), low-grade dysplasia (LGD, n=30), high-grade dysplasia (HGD, n=13), mixed LGD/HGD (n=7) and CA-CRC (n=19). Phylogenetic trees were reconstructed, and evolutionary analysis used to reveal the temporal sequence of events leading to CA-CRC.\n\n10/12 tumors were microsatellite stable with a median mutation burden of 3.0 single nucleotide alterations (SNAs) per Mb, around 20% higher than S-CRC (2.5 SNAs/Mb), and consistent with elevated aging-associated mutational processes. Non-dysplastic mucosa had considerable mutation burden (median 47 SNAs), including mutations shared with the neighboring CA-CRC, indicating a pre-cancer mutational field. CA-CRCs were often near-triploid (42%) or near-tetraploid (21%) and phylogenetic analysis revealed that copy number alterations (CNAs) began to accrue in non-dysplastic bowel, but the LGD/HGD transition often involved a punctuated catastrophic CNA increase.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-25T14:47:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003029","title":"Identification of recurrent mutations in Cushing’s disease","description":"The overall goal of the Identification of recurrent mutations in Cushing’s disease project is to study the impact of whole-exome sequencing (WES) on the clinical care of cancer patients and oncology provider practices. The aims of Project are to implement and establish the feasibility of WES in patients with USP8 wild-type corticotroph adenomas; to develop a framework for understanding of the molecular mechanism of the pathogenesis of corticotroph adenoma.","abstract":"The overall goal of the Identification of recurrent mutations in Cushing’s disease project is to study the impact of whole-exome sequencing (WES) on the clinical care of cancer patients and oncology provider practices. The aims of Project are to implement and establish the feasibility of WES in patients with USP8 wild-type corticotroph adenomas; to develop a framework for understanding of the molecular mechanism of the pathogenesis of corticotroph adenoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-28T04:25:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003030","title":"SPATC1L variants in hereditary and age-related hearing loss patients.","description":"Next-generation sequencing techniques revealed three variants in SPATC1L in one Italian family affected by hereditary hearing loss and in two Italian patients affected by age-related hearing loss.","abstract":"Next-generation sequencing techniques revealed three variants in SPATC1L in one Italian family affected by hereditary hearing loss and in two Italian patients affected by age-related hearing loss.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003031","title":"Patient-derived neuroblastoma model system OHC-NB1","description":"Accurate disease modeling presents a bottleneck against effective translation of novel neuroblastoma therapies into the clinic. Recently, considerable intra-tumor genetic heterogeneity has been observed in neuroblastoma, which calls for preclinical models that reflect this feature. Flexibility in a testing platform is also desirable to support assessment of different endpoints and tumor cell characteristics. We present the novel neuroblastoma model OHC-NB1, propagated from a bone marrow metastasis from a patient with INRG stage M, MYCN-amplified neuroblastoma at first diagnosis. To model different aspects of the disease, several preclinical models were developed from the bone marrow aspirate: a tissue plastic-adherent cell line, a 3-dimensional (3D) spheroid culture, and cell line-derived xenografts that were subcutaneously passaged in mice. Typical aspects of MYCN-amplified neuroblastoma, such as MYCN amplification in double minutes, 1p deletion, 17q gain, and a diploid karyotype, are present in OHC-NB1 and persist in all culture types. Whole exome sequencing revealed intra-tumor heterogeneity in the bone marrow metastasis reflected in the culture models. The set of OHC-NB1 cultures with a genetically heterogeneous MYCN-amplified neuroblastoma background provide a flexible preclinical testing system that recapitulates important features of metastatic neuroblastoma.","abstract":"Accurate disease modeling presents a bottleneck against effective translation of novel neuroblastoma therapies into the clinic. Recently, considerable intra-tumor genetic heterogeneity has been observed in neuroblastoma, which calls for preclinical models that reflect this feature. Flexibility in a testing platform is also desirable to support assessment of different endpoints and tumor cell characteristics. We present the novel neuroblastoma model OHC-NB1, propagated from a bone marrow metastasis from a patient with INRG stage M, MYCN-amplified neuroblastoma at first diagnosis. To model different aspects of the disease, several preclinical models were developed from the bone marrow aspirate: a tissue plastic-adherent cell line, a 3-dimensional (3D) spheroid culture, and cell line-derived xenografts that were subcutaneously passaged in mice. Typical aspects of MYCN-amplified neuroblastoma, such as MYCN amplification in double minutes, 1p deletion, 17q gain, and a diploid karyotype, are present in OHC-NB1 and persist in all culture types. Whole exome sequencing revealed intra-tumor heterogeneity in the bone marrow metastasis reflected in the culture models. The set of OHC-NB1 cultures with a genetically heterogeneous MYCN-amplified neuroblastoma background provide a flexible preclinical testing system that recapitulates important features of metastatic neuroblastoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-30T15:04:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003032","title":"Capture Hi-C on Hodgkin lymphoma cell line L-428","description":"In situ promoter capture Hi-C on Hodgkin lymphoma cell line L-428 in experimental triplicates. Hi-C libraries were prepared as previously described (Orlando et al., 2018, https://currentprotocols.onlinelibrary.wiley.com/doi/pdf/10.1002/cphg.63). Promoter capture was based on 32,313 biotinylated 120-mer RNA baits (Agilent). Hi-C libraries were sequenced using Illumina HiSeq 2000 technology. The files are in FASTQ format.","abstract":"In situ promoter capture Hi-C on Hodgkin lymphoma cell line L-428 in experimental triplicates. Hi-C libraries were prepared as previously described (Orlando et al., 2018, https://currentprotocols.onlinelibrary.wiley.com/doi/pdf/10.1002/cphg.63). Promoter capture was based on 32,313 biotinylated 120-mer RNA baits (Agilent). Hi-C libraries were sequenced using Illumina HiSeq 2000 technology. The files are in FASTQ format.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-31T11:21:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003033","title":"ChIP-seq data of Hodgkin lymphoma cell line L-428","description":"ChIP-seq data (H3K4Me3, H3K27Ac histone modifications) of Hodgkin lymphoma cell line L-428. Samples were processed as previously described (Sud et al., 2018). The files are in bam format, aligned to build 37.","abstract":"ChIP-seq data (H3K4Me3, H3K27Ac histone modifications) of Hodgkin lymphoma cell line L-428. Samples were processed as previously described (Sud et al., 2018). The files are in bam format, aligned to build 37.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-05-31T11:28:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003034","title":"Somatic mutations in colorectal cancer (whole-genome data)","description":"Cohesin is present in almost all active enhancer regions, where it is associated with transcription factors. Cohesin frequently colocalizes with CTCF (CCCTC-binding factor), affecting genomic stability, expression and epigenetic homeostasis. Cohesin subunits are mutated in cancer, but CTCF/cohesin-binding sites (CBSs) in DNA have not been examined for mutations. Here we report frequent mutations at CBSs in cancers displaying a mutational signature where mutations in A•T base pairs predominate. Integration of whole-genome sequencing data from 213 colorectal cancer (CRC) samples and chromatin immunoprecipitation sequencing (ChIP-exo) data identified frequent point mutations at CBSs. In contrast, CRCs showing an ultramutator phenotype caused by defects in the exonuclease domain of DNA polymerase ? (POLE) displayed significantly fewer mutations at and adjacent to CBSs. Analysis of public data showed that multiple cancer types accumulate CBS mutations. CBSs are a major mutational hotspot in the noncoding cancer genome.","abstract":"Cohesin is present in almost all active enhancer regions, where it is associated with transcription factors. Cohesin frequently colocalizes with CTCF (CCCTC-binding factor), affecting genomic stability, expression and epigenetic homeostasis. Cohesin subunits are mutated in cancer, but CTCF/cohesin-binding sites (CBSs) in DNA have not been examined for mutations. Here we report frequent mutations at CBSs in cancers displaying a mutational signature where mutations in A•T base pairs predominate. Integration of whole-genome sequencing data from 213 colorectal cancer (CRC) samples and chromatin immunoprecipitation sequencing (ChIP-exo) data identified frequent point mutations at CBSs. In contrast, CRCs showing an ultramutator phenotype caused by defects in the exonuclease domain of DNA polymerase ɛ (POLE) displayed significantly fewer mutations at and adjacent to CBSs. Analysis of public data showed that multiple cancer types accumulate CBS mutations. CBSs are a major mutational hotspot in the noncoding cancer genome.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003035","title":"AUBTRG - Whole Exome Sequencing of Diffuse Glioma Samples","description":null,"abstract":"Through whole exome sequencing of tumor-normal pairs, Acibadem University - Brain Tumor Research Group (AUBTRG) aims to determine germline and somatic alterations in diffuse gliomas and analyze these variants to reach clinically relevant conclusions.","study_type":"Cancer Genomics","pubmed_ids":[30952131],"external_links":null,"is_released":true,"released_date":"2018-06-02T10:45:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003036","title":"Urine DNA based cancer detection","description":"Urine DNA based cancer detection","abstract":"Urine DNA based cancer detection","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003037","title":"Canadian prostate cancer samples (CPC-GENE) for PanProstate study","description":"CPC-GENE has sequenced the genomes of 350 intermediate risk prostate cancers to identify genetic signatures that differ in cancers that responded well to treatment compared with those that did not.  CPC-GENE also has sequenced multiple regions of prostate cancer from the same gland to determine if and how the genetic make-up of prostate cancer varies within an individual man’s prostate","abstract":"CPC-GENE has sequenced the genomes of 350 intermediate risk prostate cancers to identify genetic signatures that differ in cancers that responded well to treatment compared with those that did not.  CPC-GENE also has sequenced multiple regions of prostate cancer from the same gland to determine if and how the genetic make-up of prostate cancer varies within an individual man’s prostate","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-04T16:35:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003038","title":"Recurrent loss of heterozygosity correlates with clinical outcome in pancreatic neuroendocrine cancer","description":"Pancreatic neuroendocrine tumors (pNETs) are uncommon cancers arising from pancreatic islet cells. Here we report analysis of gene mutation, copy number and RNA expression of 57 sporadic well-differentiated pNETs.","abstract":"Pancreatic neuroendocrine tumors (pNETs) are uncommon cancers arising from pancreatic islet cells. Here we report analysis of gene mutation, copy number and RNA expression of 57 sporadic well-differentiated pNETs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-05T05:54:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003039","title":"Saliva microbiota in Finnish children","description":"The human intestinal microbiota may play a role in the development of overweight and obesity. However, associations between saliva microbiota and body mass index (BMI) have been sparsely studied, although the oral cavity is the major gateway for microbes into the body. The aim of this study was to identify associations between the saliva microbiota and BMI categories in Finnish children aged 9-14 years.","abstract":"The human intestinal microbiota may play a role in the development of overweight and obesity. However, associations between saliva microbiota and body mass index (BMI) have been sparsely studied, although the oral cavity is the major gateway for microbes into the body. The aim of this study was to identify associations between the saliva microbiota and BMI categories in Finnish children aged 9-14 years.","study_type":"Other","pubmed_ids":[31024514],"external_links":null,"is_released":true,"released_date":"2018-06-06T07:36:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003040","title":"Exome-wide analysis identifies three low-frequency missense variants associated with pancreatic cancer risk in Chinese populations","description":"Germline coding variants have not been systematically investigated for pancreatic ductal adenocarcinoma (PDAC). Here, we report an exome-wide investigation using the Illumina Human Exome Beadchip with 943 PDAC cases and 3,908 controls in the Chinese population, followed by two independent replicate samples including 2,142 cases and 4,697 controls. We identify three low-frequency missense variants associated with the PDAC risk: rs34309238 in PKN1 (OR = 1.77, 95% CI: 1.48-2.12, P = 5.35 X 10-10), rs2242241 in DOK2 (OR = 1.85, 95% CI: 1.50-2.27, P = 4.34 X 10-9) and rs183117027 in APOB (OR = 2.34, 95% CI: 1.72-3.16, P = 4.21 X 10-8).","abstract":"Germline coding variants have not been systematically investigated for pancreatic ductal adenocarcinoma (PDAC). Here, we report an exome-wide investigation using the Illumina Human Exome Beadchip with 943 PDAC cases and 3,908 controls in the Chinese population, followed by two independent replicate samples including 2,142 cases and 4,697 controls. We identify three low-frequency missense variants associated with the PDAC risk: rs34309238 in PKN1 (OR = 1.77, 95% CI: 1.48-2.12, P = 5.35 X 10-10), rs2242241 in DOK2 (OR = 1.85, 95% CI: 1.50-2.27, P = 4.34 X 10-9) and rs183117027 in APOB (OR = 2.34, 95% CI: 1.72-3.16, P = 4.21 X 10-8).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-06T09:11:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003041","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___GI___Chemotherapy___WGS","description":"Somatic mutations (burdens and signatures) and clonal dynamics in normal human tissues from the gastrointestinal tract of individuals exposed to chemotherapy and other known genotoxins.","abstract":"The aim of this project is to investigate somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the study of normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to identify and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003042","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___GI___Chemotherapy___TGS","description":"Somatic mutations (driver mutations) and clonal dynamics in normal human tissues from the gastrointestinal tract of individuals exposed to chemotherapy and other known genotoxins.","abstract":"The aim of this project is to investigate somatic mutations and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the study of normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to identify and isolate specific cell populations which are then subjected to targeted genome sequencing to describe driver mutation frequency and clonal expansions in normal tissues.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003043","title":"Evolutionary dynamics of residual disease in human glioblastoma","description":"Glioblastoma is the most common and aggressive adult brain malignancy against which conventional surgery and chemoradiation provide limited benefit. Even when a good treatment response is obtained, recurrence inevitably occurs either locally (c.80%) or distally (c.20%), driven by cancer clones that are often genomically distinct from those in the primary tumour. Glioblastoma cells display a characteristic infiltrative phenotype, invading the surrounding tissue and often spreading across the whole brain. We hypothesised that cancer cells responsible for relapse reside in two compartments of residual disease that are left behind after treatment: the infiltrated normal brain parenchyma, and the sub-ventricular zone (SVZ). In this model, residual disease subclones diverge early during glioblastoma evolution, may remain dormant in the normal parenchyma and are responsible for recurrence. To test our hypothesis, we performed whole-exome sequencing of 69 multi- region samples collected using fluorescence-guided resection from 11 patients, including the infiltrating tumour margin (M) and the SVZ for each patient, as well as matched blood. We used a phylogenomic approach to dissect the spatio-temporal evolution of each tumour and unveil the relation between residual disease and the main tumour mass. We also analysed two patients with paired primary-recurrence samples with matched residual disease. Our results suggest that the infiltrative phenotype is an early evolutionary trait of glioblastoma, giving rise to the tumour mass detected at surgery. After treatment, the same infiltrative clone may seed the growth of a recurrent tumour, thus representing the ‘missing link’ between the primary tumour and recurrent disease. These results are consistent with recognised clinical phenotypic behaviour and suggest that more specific therapeutic targeting of cells in the infiltrated brain parenchyma may improve patient’s outcome.","abstract":"Glioblastoma is the most common and aggressive adult brain malignancy against which conventional surgery and chemoradiation provide limited benefit. Even when a good treatment response is obtained, recurrence inevitably occurs either locally (c.80%) or distally (c.20%), driven by cancer clones that are often genomically distinct from those in the primary tumour. Glioblastoma cells display a characteristic infiltrative phenotype, invading the surrounding tissue and often spreading across the whole brain. We hypothesised that cancer cells responsible for relapse reside in two compartments of residual disease that are left behind after treatment: the infiltrated normal brain parenchyma, and the sub-ventricular zone (SVZ). In this model, residual disease subclones diverge early during glioblastoma evolution, may remain dormant in the normal parenchyma and are responsible for recurrence. To test our hypothesis, we performed whole-exome sequencing of 69 multi- region samples collected using fluorescence-guided resection from 11 patients, including the infiltrating tumour margin (M) and the SVZ for each patient, as well as matched blood. We used a phylogenomic approach to dissect the spatio-temporal evolution of each tumour and unveil the relation between residual disease and the main tumour mass. We also analysed two patients with paired primary-recurrence samples with matched residual disease. Our results suggest that the infiltrative phenotype is an early evolutionary trait of glioblastoma, giving rise to the tumour mass detected at surgery. After treatment, the same infiltrative clone may seed the growth of a recurrent tumour, thus representing the ‘missing link’ between the primary tumour and recurrent disease. These results are consistent with recognised clinical phenotypic behaviour and suggest that more specific therapeutic targeting of cells in the infiltrated brain parenchyma may improve patient’s outcome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-06T09:29:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003044","title":"16S rRNA gene amplification and maternal factors","description":"Human breast milk contains a diverse community of bacteria but factors that produce variation in the breast milk microbiome are largely unknown. We evaluated if 1) maternal factors including breastfeeding practices modified the diversity and abundance of bacterial communities in breast milk and 2) if subclinical mastitis (SCM), an asymptomatic inflammatory condition occurring during lactation, induced a distinctive microbiota signature.","abstract":"Human breast milk contains a diverse community of bacteria but factors that produce variation in the breast milk microbiome are largely unknown. We evaluated if 1) maternal factors including breastfeeding practices modified the diversity and abundance of bacterial communities in breast milk and 2) if subclinical mastitis (SCM), an asymptomatic inflammatory condition occurring during lactation, induced a distinctive microbiota signature.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-06T11:14:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003045","title":"Lone atrial fibrillation case-control study","description":null,"abstract":"Targeted sequencing, W/ TruSight Cardio Sequencing Kit. 395 'lone' AF cases and 375 controls.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003046","title":"Targeted re-sequencing and whole exome sequencing for the study of hereditary and age-related hearing loss.","description":"Next-generation sequencing techniques (i.e, targeted re-sequencing and whole exome sequencing) have been employed for the study of an Italian family affected by hereditary hearing loss and two Italian patients affected by age-related hearing loss. Data analysis led to the identification of three variants in SPATC1L, associated with the clinical phenotype.","abstract":"Next-generation sequencing techniques (i.e, targeted re-sequencing and whole exome sequencing) have been employed for the study of an Italian family affected by hereditary hearing loss and two Italian patients affected by age-related hearing loss. Data analysis led to the identification of three variants in SPATC1L, associated with the clinical phenotype.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003047","title":"SPATC1L variants associated with age-related and hereditary hearing loss","description":"Next-Generation Sequencing techniques (i.e, targeted re-sequencing and whole exome sequencing) have been employed for the study of two Italian patients affected by age-related hearing loss and of an Italian family affected by hereditary hearing loss. Data analysis led to the identification of three variants in SPATC1L, associated with the clinical phenotype.","abstract":"Next-Generation Sequencing techniques (i.e, targeted re-sequencing and whole exome sequencing) have been employed for the study of two Italian patients affected by age-related hearing loss and of an Italian family affected by hereditary hearing loss. Data analysis led to the identification of three variants in SPATC1L, associated with the clinical phenotype.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-06T13:58:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003048","title":"Whole exome DNA sequence profiling of spatial biopsies of high grade serous epithelial ovarian cancer","description":"The study aims at dissecting the heterogeneity across multiple biopsies of high grade serous epithelial ovarian cancer (HGS-EOC) through a comprehensive characterization of variants and structural changes at the whole exome level. To this aim, the study uses samples from multiple bioptic sites taken from eight HGS-EOC patients.","abstract":"The study aims at dissecting the heterogeneity across multiple biopsies of high grade serous epithelial ovarian cancer (HGS-EOC) through a comprehensive characterization of variants and structural changes at the whole exome level. To this aim, the study uses samples from multiple bioptic sites taken from eight HGS-EOC patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-07T09:46:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003049","title":"Microdissection_sequencing_of_normal_human_prostate","description":"Histology sections from pathologically benign human prostates were prepared and microdissections retrieved from Laser-Capture Microdissection are submitted to low-input whole-genome sequencing.","abstract":"Recent work by Moad and colleagues based on tracking a sporadic mitochondrial DNA mutation demonstrated that the two different layers in the epithelial ducts share the same progenitor cells, located the stem cell niche in the juxta-urethral part of the ducts and proposed a model of directed, long-ranging progenitor cell flow for duct maintenance. We would like to build on these findings and complement it with an approach using laser-capture microdissection followed by whole-genome sequencing. We propose to create phylogenetic maps of 10 – 20 ductal-glandular subunits from a single histologically benign prostate. Image acquisition and reconstruction will allow us to create anatomical trees that display the complex branching pattern of the ductal- glandular system similar to Moad et. al8. We envision sampling a sufficient number of acini that by pairwise comparison of anatomically more closely and more distantly related acini will inform a lineage tree on every main branching level. This phylogenetic tree will be merged or compared to the anatomical tree to give insights into the stem cell dynamics within ductal-glandular subunits on a whole-genome level. In addition to acinus sequencing, a small number of microdissections and corresponding whole-genome sequences will be acquired throughout the ductal system to monitor clonality, mutation acquisition and burden along the proposed flow of progenitor cells. Subsequently, a bait set based on the detected mutations can be designed to allow more thorough genotyping of these mutations throughout the ductal system. This will enable us to infer the relative contribution of individual stem and progenitor cells to duct maintenance as well as to monitor the frequency of mutation acquisition. We are aiming to characterize ductal-glandular subunits from different prostate zones to capture differences in stem cell dynamics and mutational processes that could help to explain the variable incidence of prostate diseases in different zones.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-07T17:00:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003050","title":"RNA-seq in acute sleep loss in humans","description":"Curtailed sleep promotes weight gain and loss of lean mass in humans, though the underlying molecular mechanisms are poorly understood. Here, we investigated the genomic and physiological impact of acute sleep loss in peripheral tissues, by obtaining adipose tissue and skeletal muscle after one night of sleep loss and after one full night of sleep. We find that acute sleep loss alters genome-wide DNA methylation in adipose tissue, and unbiased transcriptomic-, protein- and metabolite-level analyses also reveal highly tissue-specific changes that are partially reflected by altered metabolite levels in blood. We observe transcriptomic signatures of inflammation in both tissues following acute sleep loss, but changes involving the circadian clock are evident only in skeletal muscle, and we uncover molecular signatures suggestive of muscle breakdown that contrast with an anabolic adipose tissue signature. Our findings provide insight into how disruption of sleep and circadian rhythms may promote weight gain and sarcopenia.","abstract":"Curtailed sleep promotes weight gain and loss of lean mass in humans, though the underlying molecular mechanisms are poorly understood. Here, we investigated the genomic and physiological impact of acute sleep loss in peripheral tissues, by obtaining adipose tissue and skeletal muscle after one night of sleep loss and after one full night of sleep. We find that acute sleep loss alters genome-wide DNA methylation in adipose tissue, and unbiased transcriptomic-, protein- and metabolite-level analyses also reveal highly tissue-specific changes that are partially reflected by altered metabolite levels in blood. We observe transcriptomic signatures of inflammation in both tissues following acute sleep loss, but changes involving the circadian clock are evident only in skeletal muscle, and we uncover molecular signatures suggestive of muscle breakdown that contrast with an anabolic adipose tissue signature. Our findings provide insight into how disruption of sleep and circadian rhythms may promote weight gain and sarcopenia.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003051","title":"WGS___Genomic_profiling_of_relapse_in_Adult_ALL","description":"Whole genome sequencing on Illumina X10 machines of up to 30 Adult ALL triplet (diagnosis/remission/relapse) sample sets","abstract":"Adult ALL is an aggressive leukaemia, affecting adults of all ages. It is associated with a rapid onset and poor outcomes.  Our understanding of adult ALL genome has been limited to molecular markers first described in paediatric ALL and validated in adult ALL. We will explore the clonal origins of relapsed ALL in adults by WGS in triplet (diagnosis/remission/relapse) sample sets. This will deliver a comprehensive annotation of the genomic landscape of relapsed Adult ALL to include acquired somatic mutations (substitutions, indels, structural variants/fusion genes) and copy number profiles.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003052","title":"_RNA___Genomic_profiling_of_relapse_in_Adult_ALL","description":"Rna-seq on up to 30 Adult ALL triplet (diagnosis/remission/relapse) sample sets","abstract":"Adult ALL is an aggressive leukaemia, affecting adults of all ages. It is associated with a rapid onset and poor outcomes.  Our understanding of adult ALL genome has been limited to molecular markers first described in paediatric ALL and validated in adult. We will explore the transcriptome of relapsed ALL in adults by RNA-seq in triplet (diagnosis/remission/relapse) sample sets. This will deliver a comprehensive annotation of the transcriptomic landscape of relapsed Adult ALL to include differential expression and quantification of fusion genes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003053","title":"WES analysis in identifying additive genetic factors that may contribute to the occurrence of moyamoya in neurofibromatosis type 1","description":"Moyamoya is a progressive cerebral vasculopathy, for which genetic susceptibility factors were mainly identified in Asian populations. When associated with other medical conditions, such as neurofibromatosis type 1 (NF1), this vasculopathy is frequently reported as Moyamoya syndrome (MMS). Intriguingly, most cases of MMS-complicated NF1 have been described in Caucasians, inverting the population ratio for moyamoya vasculopathy observed in Asians, despite NF1 prevalence being constant worldwide.\nThis study aims to investigate whether, among Caucasians, additive genetic factors may contribute to the occurrence of MMS in NF1. WES analysis has been carried out on an Italian family with co-occurrence of NF1 and MMS, as well as other cerebral vasculopathies.","abstract":"Moyamoya is a progressive cerebral vasculopathy, for which genetic susceptibility factors were mainly identified in Asian populations. When associated with other medical conditions, such as neurofibromatosis type 1 (NF1), this vasculopathy is frequently reported as Moyamoya syndrome (MMS). Intriguingly, most cases of MMS-complicated NF1 have been described in Caucasians, inverting the population ratio for moyamoya vasculopathy observed in Asians, despite NF1 prevalence being constant worldwide.\nThis study aims to investigate whether, among Caucasians, additive genetic factors may contribute to the occurrence of MMS in NF1. WES analysis has been carried out on an Italian family with co-occurrence of NF1 and MMS, as well as other cerebral vasculopathies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-09T19:52:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003054","title":"Indonesian Genome Diversity Project","description":"Indonesia, the world’s fourth largest country by population, comprises an archipelago of about 900 permanently inhabited islands in tropical Asia, and hosts an astonishing array of human diversity that remains largely underrepresented in modern biological surveys. The region is unique for its key role in both the early and recent evolution of Homo outside of Africa. It has one of the first traces of anatomically modern humans in Eurasia, and was the focus of extensive interaction between archaic hominins and humans – both in the likely co-existence of H. floresiensis with modern humans, and in the introgression of Denisovans into the ancestors of its present inhabitants. More recently, Indonesia was a center of the spread of Neolithic culture by Austronesian speakers. Advancing maritime technologies allowed farming populations to treat this region as a springboard to reach oceanic islands as remote as Madagascar, Hawaii, Easter Island and New Zealand. Here we present complete human genomes from healthy individuals from multiple key islands in Indonesia and Papua. The genomes were sequenced to high depth (30x). The purpose of this dataset is to address different questions of human evolution in Island Southeast Asia and beyond, including early settlement of the area by anatomically modern humans, population structure, genetic admixture and adaptation, and contacts with archaic hominins. We employed a sampling strategy to capture a broad range of diversity across the region incorporating an average of 12 samples from each of 14 islands spanning Indonesia and Papua, from Sumatra in the west to New Britain in the east. Genomes from this dataset form part of an ongoing project to describe and understand human evolutionary history in Island Southeast Asia and Eurasia in general.","abstract":"Indonesia, the world’s fourth largest country by population, comprises an archipelago of about 900 permanently inhabited islands in tropical Asia, and hosts an astonishing array of human diversity that remains largely underrepresented in modern biological surveys. The region is unique for its key role in both the early and recent evolution of Homo outside of Africa. It has one of the first traces of anatomically modern humans in Eurasia, and was the focus of extensive interaction between archaic hominins and humans – both in the likely co-existence of H. floresiensis with modern humans, and in the introgression of Denisovans into the ancestors of its present inhabitants. More recently, Indonesia was a center of the spread of Neolithic culture by Austronesian speakers. Advancing maritime technologies allowed farming populations to treat this region as a springboard to reach oceanic islands as remote as Madagascar, Hawaii, Easter Island and New Zealand. Here we present complete human genomes from healthy individuals from multiple key islands in Indonesia and Papua. The genomes were sequenced to high depth (30x). The purpose of this dataset is to address different questions of human evolution in Island Southeast Asia and beyond, including early settlement of the area by anatomically modern humans, population structure, genetic admixture and adaptation, and contacts with archaic hominins. We employed a sampling strategy to capture a broad range of diversity across the region incorporating an average of 12 samples from each of 14 islands spanning Indonesia and Papua, from Sumatra in the west to New Britain in the east. Genomes from this dataset form part of an ongoing project to describe and understand human evolutionary history in Island Southeast Asia and Eurasia in general.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-10T09:12:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003055","title":"A whole exome sequencing approach to defining the genetic risk factors for Achilles tendinopathy","description":"Musculoskeletal soft tissue injuries are complex phenotypes. Case-control association studies using the candidate gene approach have predominantly been used to identify risk loci for these injuries. However, the ability to identify all risk conferring variants using this approach alone is unlikely. Therefore, this study aimed to define the genetic profile of these injuries using whole exome sequencing and a customized analysis pipeline. The exomes of ten exemplar asymptomatic controls and ten exemplar cases with Achilles tendinopathy were individually sequenced using a platform that included the coverage of the untranslated regions and miRBase miRNA genes. These results provide a proof of concept for the use of a customized pipeline for the exploration of a larger genomic dataset. This approach, using previous research to guide a targeted analysis of the data has generated new genetic signatures in the biology of musculoskeletal soft tissue injuries","abstract":"Musculoskeletal soft tissue injuries are complex phenotypes. Case-control association studies using the candidate gene approach have predominantly been used to identify risk loci for these injuries. However, the ability to identify all risk conferring variants using this approach alone is unlikely. Therefore, this study aimed to define the genetic profile of these injuries using whole exome sequencing and a customized analysis pipeline. The exomes of ten exemplar asymptomatic controls and ten exemplar cases with Achilles tendinopathy were individually sequenced using a platform that included the coverage of the untranslated regions and miRBase miRNA genes. These results provide a proof of concept for the use of a customized pipeline for the exploration of a larger genomic dataset. This approach, using previous research to guide a targeted analysis of the data has generated new genetic signatures in the biology of musculoskeletal soft tissue injuries","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003056","title":"HCA_Muscle_sNuclei","description":"Single cells and single nuclei are isolated from human skeletal muscles and purified with percoll gradient centrifugation.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The goal of this study is to understand the molecuar regulation of human skeletaml muscle development and maintainance.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003057","title":"SNP array genome charaterization of GCATcore, a subset of the GCAT cohort.","description":"The GCAT Study is a long-term genomic, environmental and lifestyle cohort project that aims to evaluate and track multiple pathologies as well as biologically related traits. Therefore, the GCAT Study offers a unique opportunity to integrate diverse data to allow the identification of novel relations among different biomarkers and conditions. Results may lead to the development of new genetic, genomic, epigenomic and proteomic diagnoses and screening tests, as well as new public health recommendations.\nGCAT is the only currently available population-based prospective cohort study in Spain with more than 5500 genotyped participants and 800 whole genome sequences.","abstract":"The GCAT Study is a long-term genomic, environmental and lifestyle cohort project that aims to evaluate and track multiple pathologies as well as biologically related traits. Therefore, the GCAT Study offers a unique opportunity to integrate diverse data to allow the identification of novel relations among different biomarkers and conditions. Results may lead to the development of new genetic, genomic, epigenomic and proteomic diagnoses and screening tests, as well as new public health recommendations.\nGCAT is the only currently available population-based prospective cohort study in Spain with more than 5500 genotyped participants and 800 whole genome sequences.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003058","title":"CCND1-negative MCL","description":"A subset of CCND1-negative mantle cell lymphoma MCL (CCND1- MCL) has been recognized, and around half of them harbor CCND2 translocations. To identify other potential mechanisms driving MCL pathogenesis we investigated CCND1?  MCL by by whole genome/exome sequencing. We identified a cryptic insertion of IGK and IGL enhancer regions near the CCND3 gene in three cases. Specific FISH probes detected 10 additional cryptic IGK juxtapositions to CCND3 (6 cases) and CCND2 (4 cases). In conclusion, virtually all CCND1-/SOX11+ MCL carry CCND2/CCND3 rearrangement with IG genes, including cryptic IGK/L enhancer regions not detected with currently used FISH probes.","abstract":"A subset of CCND1-negative mantle cell lymphoma MCL (CCND1- MCL) has been recognized, and around half of them harbor CCND2 translocations. To identify other potential mechanisms driving MCL pathogenesis we investigated CCND1−  MCL by by whole genome/exome sequencing. We identified a cryptic insertion of IGK and IGL enhancer regions near the CCND3 gene in three cases. Specific FISH probes detected 10 additional cryptic IGK juxtapositions to CCND3 (6 cases) and CCND2 (4 cases). In conclusion, virtually all CCND1-/SOX11+ MCL carry CCND2/CCND3 rearrangement with IG genes, including cryptic IGK/L enhancer regions not detected with currently used FISH probes.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003059","title":"Brugada Syndrome-associated Genetic Loci are associated with J-point Elevation and an Increased Risk of Cardiac Arrest","description":"Introduction: A previous genome-wide association study found three genetic loci, rs9388451, rs10428132, and rs11708996, toincrease the risk of Brugada Syndrome (BrS). Since the effect of these loci in the general population is unknown, we aimed toinvestigate the effect on electrocardiogram (ECG) parameters and outcomes in the general population.Material and Methods: A cohort of 6,161 individuals (median age 45 [interquartile range (IQR) 40-50] years, 49% males), withavailable digital ECGs, was genotyped and subsequently followed for a median period of 13 [IQR 12.6-13.4] years. Data on outcomeswere collected from Danish administrative healthcare registries. Furthermore, ~400.000 persons from UK Biobank wereinvestigated for associations between the three loci and cardiac arrest/ventricular fibrillation (VF).Results: Homozygote carriers of the C allele in rs6800541 intronic to SCN10A had a significantly larger J-point elevation (JPE)compared with wildtype carriers (11 V vs 6 V, P&lt;0.001). There was an additive effect of carrying multiple BrS-associated riskalleles with an increased JPE in lead V1. None of the BrS‐associated genetic loci predisposed to syncope, atrial fibrillation, or totalmortality in the general population of Denmark. The rs9388451 genetic locus adjacent to the HEY2 gene was associated withcardiac arrest/VF in an analysis using the UK Biobank study (odds ratio=1.13 (95% confidence interval: 1.08-1.18), P=0.006).Conclusions: BrS-associated risk alleles increase the JPE in lead V1 in an additive manner, but was not associated with increasedmortality or syncope in the general population of Denmark. However, the HEY2 risk allele increased the risk of cardiac arrest/ VFin the larger population study of UK Biobank indicating an important role of this common genetic locus.","abstract":"Introduction: A previous genome-wide association study found three genetic loci, rs9388451, rs10428132, and rs11708996, toincrease the risk of Brugada Syndrome (BrS). Since the effect of these loci in the general population is unknown, we aimed toinvestigate the effect on electrocardiogram (ECG) parameters and outcomes in the general population.Material and Methods: A cohort of 6,161 individuals (median age 45 [interquartile range (IQR) 40-50] years, 49% males), withavailable digital ECGs, was genotyped and subsequently followed for a median period of 13 [IQR 12.6-13.4] years. Data on outcomeswere collected from Danish administrative healthcare registries. Furthermore, ~400.000 persons from UK Biobank wereinvestigated for associations between the three loci and cardiac arrest/ventricular fibrillation (VF).Results: Homozygote carriers of the C allele in rs6800541 intronic to SCN10A had a significantly larger J-point elevation (JPE)compared with wildtype carriers (11 V vs 6 V, P&lt;0.001). There was an additive effect of carrying multiple BrS-associated riskalleles with an increased JPE in lead V1. None of the BrS‐associated genetic loci predisposed to syncope, atrial fibrillation, or totalmortality in the general population of Denmark. The rs9388451 genetic locus adjacent to the HEY2 gene was associated withcardiac arrest/VF in an analysis using the UK Biobank study (odds ratio=1.13 (95% confidence interval: 1.08-1.18), P=0.006).Conclusions: BrS-associated risk alleles increase the JPE in lead V1 in an additive manner, but was not associated with increasedmortality or syncope in the general population of Denmark. However, the HEY2 risk allele increased the risk of cardiac arrest/ VFin the larger population study of UK Biobank indicating an important role of this common genetic locus.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003060","title":"CCND1-negative MCL","description":"A subset of CCND1-negative mantle cell lymphoma MCL (CCND1- MCL) has been recognized, and around half of them harbor CCND2 translocations. To identify other potential mechanisms driving MCL pathogenesis we investigated CCND1−  MCL by by whole genome/exome sequencing. We identified a cryptic insertion of IGK and IGL enhancer regions near the CCND3 gene in three cases. Specific FISH probes detected 10 additional cryptic IGK juxtapositions to CCND3 (6 cases) and CCND2 (4 cases). In conclusion, virtually all CCND1-/SOX11+ MCL carry CCND2/CCND3 rearrangement with IG genes, including cryptic IGK/L enhancer regions not detected with currently used FISH probes.","abstract":"A subset of CCND1-negative mantle cell lymphoma MCL (CCND1- MCL) has been recognized, and around half of them harbor CCND2 translocations. To identify other potential mechanisms driving MCL pathogenesis we investigated CCND1−  MCL by by whole genome/exome sequencing. We identified a cryptic insertion of IGK and IGL enhancer regions near the CCND3 gene in three cases. Specific FISH probes detected 10 additional cryptic IGK juxtapositions to CCND3 (6 cases) and CCND2 (4 cases). In conclusion, virtually all CCND1-/SOX11+ MCL carry CCND2/CCND3 rearrangement with IG genes, including cryptic IGK/L enhancer regions not detected with currently used FISH probes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-14T11:04:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003061","title":"MiR-223 in stool as a biomarker for early detection of colorectal cancer","description":"Colorectal cancer (CRC) arises from the epithelium that forms the inner lining of the bowel wall and progresses in a multistep process, via a premalignant stage called adenoma, towards cancer. Underlying this evolution are disruptions of critical biological processes, the status of which is reflected by changes at the DNA, RNA and protein level. Screening, i.e. early detection and removal of lesions, is the best approach to decrease the high number of CRC deaths. Most countries applying programmatic CRC screening have selected a hemoglobin-based stool test, the Fecal immunochemical Test (FIT). Furthermore, combining molecular markers with FIT in stool based secondary prevention tests can improve the diagnostic yield. However, the optimal set of molecular markers to implement in population based programmatic screening remains to be determined. The present study sets out to identify miRNAs that can be used to discriminate stool samples from CRC patients, patients with adenomas and control individuals. In this study, differences in miRNA expression levels were first determined in 30 CRC and 30 adenoma tissues by Next Generation Sequencing (NGS). Subsequent validation was performed on 55 independent CRC and 73 adenomas tissue samples by RT-qPCR. The performance of the identified miRNAs as potential biomarkers in stool samples was assessed by RT-qPCR in 430 stool samples (from 213 CRC, 53 advanced adenoma, and 55 non-advanced adenoma patients and 109 controls).","abstract":"Colorectal cancer (CRC) arises from the epithelium that forms the inner lining of the bowel wall and progresses in a multistep process, via a premalignant stage called adenoma, towards cancer. Underlying this evolution are disruptions of critical biological processes, the status of which is reflected by changes at the DNA, RNA and protein level. Screening, i.e. early detection and removal of lesions, is the best approach to decrease the high number of CRC deaths. Most countries applying programmatic CRC screening have selected a hemoglobin-based stool test, the Fecal immunochemical Test (FIT). Furthermore, combining molecular markers with FIT in stool based secondary prevention tests can improve the diagnostic yield. However, the optimal set of molecular markers to implement in population based programmatic screening remains to be determined. The present study sets out to identify miRNAs that can be used to discriminate stool samples from CRC patients, patients with adenomas and control individuals. In this study, differences in miRNA expression levels were first determined in 30 CRC and 30 adenoma tissues by Next Generation Sequencing (NGS). Subsequent validation was performed on 55 independent CRC and 73 adenomas tissue samples by RT-qPCR. The performance of the identified miRNAs as potential biomarkers in stool samples was assessed by RT-qPCR in 430 stool samples (from 213 CRC, 53 advanced adenoma, and 55 non-advanced adenoma patients and 109 controls).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003062","title":"Ewings Sarcoma RNA-Seq","description":"Sarcomas are cancers of the bone and soft tissue often defined by their gene fusions.\nHowever, the timing, context, and processes by which these pathogenic fusions arise are unknown. We explored this in Ewing sarcoma, a cancer driven by EWSR1-ETS fusions, with very few cooperating mutations. Combining whole-genome sequencing with enhanced informatics, we found that the EWSR1-ETS fusion arose from striking rearrangement clusters in 42% of cases (52/124). Notably, these were organized in loops that universally contained the fusion at their center, while also weaving up to 18 genes together with it. We found the same pattern of rearrangements in three additional types of sarcoma. From these data, we define a new signature for sarcoma fusions that precedes other somatic changes, in the earliest replicating DNA of the genome. This dramatic, sudden process impinges on many genes – generating\nmultiple coding changes that profoundly affect the transcriptome, with the disease-defining gene fusion at its core. These rearrangement loops emerge in an early ES clone from which both the primary tumor and the lethal relapse emerged, and then evolved in parallel until clinically detected.","abstract":"Sarcomas are cancers of the bone and soft tissue often defined by their gene fusions.\nHowever, the timing, context, and processes by which these pathogenic fusions arise are unknown. We explored this in Ewing sarcoma, a cancer driven by EWSR1-ETS fusions, with very few cooperating mutations. Combining whole-genome sequencing with enhanced informatics, we found that the EWSR1-ETS fusion arose from striking rearrangement clusters in 42% of cases (52/124). Notably, these were organized in loops that universally contained the fusion at their center, while also weaving up to 18 genes together with it. We found the same pattern of rearrangements in three additional types of sarcoma. From these data, we define a new signature for sarcoma fusions that precedes other somatic changes, in the earliest replicating DNA of the genome. This dramatic, sudden process impinges on many genes – generating\nmultiple coding changes that profoundly affect the transcriptome, with the disease-defining gene fusion at its core. These rearrangement loops emerge in an early ES clone from which both the primary tumor and the lethal relapse emerged, and then evolved in parallel until clinically detected.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-14T17:43:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003063","title":"Whole Exome Sequencing of 60 tumor/normal matched liver Cancers (HCC)","description":"The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer). The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors using whole genome (WGS) and whole exome sequencing (WGS), integrated with DNA methylation and RNA sequencing (RNA-seq) data. The present series corresponds to 60 whole exome tumor/normal pairs with matched RNA-seq. Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem. It is the 3rd cause of cancer-related mortality. Advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. Thus, the development of next-generation sequencing technologies has made it possible to generate more comprehensive catalogues of somatic alteration events (single nucleotide substitutions, structural variations, and epigenetic changes) in liver cancer genome than ever before.","abstract":"The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer). The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors using whole genome (WGS) and whole exome sequencing (WGS), integrated with DNA methylation and RNA sequencing (RNA-seq) data. The present series corresponds to 60 whole exome tumor/normal pairs with matched RNA-seq. Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem. It is the 3rd cause of cancer-related mortality. Advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. Thus, the development of next-generation sequencing technologies has made it possible to generate more comprehensive catalogues of somatic alteration events (single nucleotide substitutions, structural variations, and epigenetic changes) in liver cancer genome than ever before.","study_type":"Other","pubmed_ids":[31206197],"external_links":null,"is_released":true,"released_date":"2018-06-15T10:29:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003064","title":"Histone chaperone CHAF1A promotes proliferation and tumorigenicity in gastric cancer and impacts prognosis via context-depedent regulation of gene expression","description":"The histone chaperone CHAF1A is associated with some tumors, but its mechanisms in tumor biology remain elusive. Gastric cancer (GC) has significant heterogeneity among patients, and novel prognostic markers and therapeutic targets may improve its outcomes. The role of CHAF1A in GC is unknown. In this study, we demonstrated that CHAF1A was overexpressed in GC tissues accompanied by low expression of wild-type P53 and high expression of the proliferation marker MKI67. In vitro, CHAF1A knockdown inhibited cell proliferation, induced cell cycle arrest and promoted apoptosis, while CHAF1A overexpression had contrary effects. In vivo, CHAF1A knockdown inhibited tumorigenicity of GC cells. A microarray assay with CHAF1A inhibition and a PathScan signaling antibody array with CHAF1A overexpression showed that CHAF1A inhibited the P53 pathway, activated stress response and induced glycolytic metabolism. In 665 patients, the expression level of CHAF1A protein was an independent predictor for overall survival and disease-free survival in non-cardia GC and also had survival associations in patients with small or perineural invasion-negative tumors. Tumor mRNA analyses based on next-generation sequencing in patients indicated that CHAF1A promoted the Warburg effect by depressing oxidative phosphorylation and increasing glycolysis. Furthermore, the heterogeneous clinical significance of CHAF1A among patient subgroups was associated with its differential regulation of gene expression involved with glycolysis and cell proliferation and survival, indicating that the role of CHAF1A is depended on patient characteristics. These results reveal critical roles and clinical values for CHAF1A in GC. CHAF1A may have context-dependent effects in GC, which increases understandings for GC heterogeneity.","abstract":"The histone chaperone CHAF1A is associated with some tumors, but its mechanisms in tumor biology remain elusive. Gastric cancer (GC) has significant heterogeneity among patients, and novel prognostic markers and therapeutic targets may improve its outcomes. The role of CHAF1A in GC is unknown. In this study, we demonstrated that CHAF1A was overexpressed in GC tissues accompanied by low expression of wild-type P53 and high expression of the proliferation marker MKI67. In vitro, CHAF1A knockdown inhibited cell proliferation, induced cell cycle arrest and promoted apoptosis, while CHAF1A overexpression had contrary effects. In vivo, CHAF1A knockdown inhibited tumorigenicity of GC cells. A microarray assay with CHAF1A inhibition and a PathScan signaling antibody array with CHAF1A overexpression showed that CHAF1A inhibited the P53 pathway, activated stress response and induced glycolytic metabolism. In 665 patients, the expression level of CHAF1A protein was an independent predictor for overall survival and disease-free survival in non-cardia GC and also had survival associations in patients with small or perineural invasion-negative tumors. Tumor mRNA analyses based on next-generation sequencing in patients indicated that CHAF1A promoted the Warburg effect by depressing oxidative phosphorylation and increasing glycolysis. Furthermore, the heterogeneous clinical significance of CHAF1A among patient subgroups was associated with its differential regulation of gene expression involved with glycolysis and cell proliferation and survival, indicating that the role of CHAF1A is depended on patient characteristics. These results reveal critical roles and clinical values for CHAF1A in GC. CHAF1A may have context-dependent effects in GC, which increases understandings for GC heterogeneity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-15T15:26:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003065","title":"Control human putamen and Substantia Nigra","description":"The study is affiliated to the UKBEC sample of healthy human putamen and substantia nigra phenotype. The gender is from both male and female samples of the the phenotype.","abstract":"The study is affiliated to the UKBEC sample of healthy human putamen and substantia nigra phenotype. The gender is from both male and female samples of the the phenotype.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-18T10:14:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003066","title":"The evolutionary landscape of colorectal tumorigenesis","description":"The genetic events that cause colorectal adenomas to progress to carcinomas remain largely undetermined. Using multi-region genome/exome sequencing of 24 benign and malignant colorectal tumours, we probe the evolutionary fitness landscape occupied by these neoplasms. Unlike carcinomas, advanced adenomas frequently harbour sub-clonal driver mutations, hence lack selective sweeps, and have relatively high genetic heterogeneity. Carcinomas are distinguished from adenomas not by nucleotide-level mutations (drivers or burden), but by widespread aneusomies that are usually clonal and often accrue in a “punctuated” fashion. Adenomas evolve across an undulating fitness landscape, whereas carcinomas occupy a sharper fitness peak, probably owing to stabilising selection.","abstract":"The genetic events that cause colorectal adenomas to progress to carcinomas remain largely undetermined. Using multi-region genome/exome sequencing of 24 benign and malignant colorectal tumours, we probe the evolutionary fitness landscape occupied by these neoplasms. Unlike carcinomas, advanced adenomas frequently harbour sub-clonal driver mutations, hence lack selective sweeps, and have relatively high genetic heterogeneity. Carcinomas are distinguished from adenomas not by nucleotide-level mutations (drivers or burden), but by widespread aneusomies that are usually clonal and often accrue in a “punctuated” fashion. Adenomas evolve across an undulating fitness landscape, whereas carcinomas occupy a sharper fitness peak, probably owing to stabilising selection.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-19T10:14:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003067","title":"hi there","description":"sadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfds","abstract":"sadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfdssadfghggfds","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003068","title":"Somatic mutations reveal lineage relationships and age-related mutagenesis in human hematopoiesis","description":"Mutation accumulation during human life can contribute to hematopoietic dysfunction; however, the underlying dynamics are unknown. Somatic mutations in  blood progenitors can provide insight into the rate and processes underlying this accumulation, as well as the developmental lineage tree and stem cell division numbers. Here, we catalogue somatic mutations in the genomes of human bone marrow-derived and cord blood-derived hematopoietic stem and multipotent progenitor cells (HSPCs) and find that base substitutions accumulate with approximately 17 base substitutions per year in both populations, while insertions and deletions occur sporadically and at low numbers. The majority of mutations in adult HSPCs were acquired after birth and could be explained by the constant activity of various endogenous processes, which also explains the mutation load in acute myeloid leukemia (AML). We construct a developmental lineage tree revealing a polyclonal architecture of the hematopoietic progenitor compartment and providing evidence that developmental clones exhibit multipotency, though lineage biases can be detected. Our approach highlights novel features of human native hematopoiesis and its implications for leukemogenesis.","abstract":"Mutation accumulation during human life can contribute to hematopoietic dysfunction; however, the underlying dynamics are unknown. Somatic mutations in  blood progenitors can provide insight into the rate and processes underlying this accumulation, as well as the developmental lineage tree and stem cell division numbers. Here, we catalogue somatic mutations in the genomes of human bone marrow-derived and cord blood-derived hematopoietic stem and multipotent progenitor cells (HSPCs) and find that base substitutions accumulate with approximately 17 base substitutions per year in both populations, while insertions and deletions occur sporadically and at low numbers. The majority of mutations in adult HSPCs were acquired after birth and could be explained by the constant activity of various endogenous processes, which also explains the mutation load in acute myeloid leukemia (AML). We construct a developmental lineage tree revealing a polyclonal architecture of the hematopoietic progenitor compartment and providing evidence that developmental clones exhibit multipotency, though lineage biases can be detected. Our approach highlights novel features of human native hematopoiesis and its implications for leukemogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-19T12:44:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003069","title":"Immunochip genetic association study of Finnish patients with chronic or recurrent tonsillitis.","description":"Pharyngeal tonsillitis is one of the most common upper respiratory tract infections and Group A streptococcus is the most important bacterial pathogen causing it. While most patients experience tonsillitis only rarely, a subset of patients suffer from recurrent or chronic tonsillitis or pharyngitis. The predisposing factors for recurring or chronic form of this disease are not yet fully understood but genetic predisposition has been suggested. A genetic association study using Illumina’s Immunochip SNP array was performed to search for new genetic biomarkers in pharyngeal tonsillitis. Over 100,000 SNPs relevant to immune-mediated diseases were analyzed in a cohort of 95 patients subjected to tonsillectomy due to recurrent/chronic tonsillitis and 504 controls. Genetic association between the cases and controls showed strongest association with two peaks in the HLA locus (OR 3.7-4.7, p=4.9-5.7x10-6). Further analysis with imputed classical HLA alleles suggested the known psoriasis risk allele HLA-C*06:02 as a risk factor for tonsillitis (p=4.8 x 10-4, OR 2.3). In addition, the imputed HLA haplotype HLA-C*06:02/HLA-B*5701, a reported risk haplotype in psoriasis, had the strongest risk for tonsillitis, too (p=8.0 x 10-3, OR 5.5). These findings further support the previously reported link between streptococcal throat infections and psoriasis.","abstract":"Pharyngeal tonsillitis is one of the most common upper respiratory tract infections and Group A streptococcus is the most important bacterial pathogen causing it. While most patients experience tonsillitis only rarely, a subset of patients suffer from recurrent or chronic tonsillitis or pharyngitis. The predisposing factors for recurring or chronic form of this disease are not yet fully understood but genetic predisposition has been suggested. A genetic association study using Illumina’s Immunochip SNP array was performed to search for new genetic biomarkers in pharyngeal tonsillitis. Over 100,000 SNPs relevant to immune-mediated diseases were analyzed in a cohort of 95 patients subjected to tonsillectomy due to recurrent/chronic tonsillitis and 504 controls. Genetic association between the cases and controls showed strongest association with two peaks in the HLA locus (OR 3.7-4.7, p=4.9-5.7x10-6). Further analysis with imputed classical HLA alleles suggested the known psoriasis risk allele HLA-C*06:02 as a risk factor for tonsillitis (p=4.8 x 10-4, OR 2.3). In addition, the imputed HLA haplotype HLA-C*06:02/HLA-B*5701, a reported risk haplotype in psoriasis, had the strongest risk for tonsillitis, too (p=8.0 x 10-3, OR 5.5). These findings further support the previously reported link between streptococcal throat infections and psoriasis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003070","title":"RNA-seq of Glioblastoma stem cells","description":"Chromatin accessibility discriminates stem from mature cell populations, enabling the identification of primitive stem-like cells in primary tumors, such as Glioblastoma (GBM) where self-renewing cells driving cancer progression and recurrence are prime targets for therapeutic intervention. We show, using single-cell chromatin accessibility, that primary GBMs harbor a heterogeneous self-renewing population whose diversity is captured in patient-derived glioblastoma stem cells (GSCs). In depth characterization of chromatin accessibility in GSCs identifies three GSC states: Reactive, Constructive, and Invasive, each governed by uniquely essential transcription factors and present within GBMs in varying proportions. Orthotopic xenografts reveal that GSC states associate with survival, and identify an invasive GSC signature predictive of low patient survival. Our chromatin-driven characterization of GSC states improves prognostic precision and identifies dependencies to guide combination therapies.","abstract":"Chromatin accessibility discriminates stem from mature cell populations, enabling the identification of primitive stem-like cells in primary tumors, such as Glioblastoma (GBM) where self-renewing cells driving cancer progression and recurrence are prime targets for therapeutic intervention. We show, using single-cell chromatin accessibility, that primary GBMs harbor a heterogeneous self-renewing population whose diversity is captured in patient-derived glioblastoma stem cells (GSCs). In depth characterization of chromatin accessibility in GSCs identifies three GSC states: Reactive, Constructive, and Invasive, each governed by uniquely essential transcription factors and present within GBMs in varying proportions. Orthotopic xenografts reveal that GSC states associate with survival, and identify an invasive GSC signature predictive of low patient survival. Our chromatin-driven characterization of GSC states improves prognostic precision and identifies dependencies to guide combination therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-21T16:24:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003071","title":"Integrative genomic analysis reveals cancer-associated mutations at diagnosis of CML in patients with high risk disease","description":"Genomic events associated with poor outcome in chronic myeloid leukemia (CML) are poorly understood. We performed whole exome sequencing, copy number variation and/or RNA-Seq for 65 patients to discover mutations at diagnosis and blast crisis (BC). Forty-six chronic phase patients with the extremes of outcome were studied at diagnosis. Cancer gene variants were detected in 15/27 patients (56%) with subsequent BC or poor outcome and in 3/19 optimal responders (16%), P=.007. Frequently mutated genes at diagnosis were ASXL1, IKZF1 and RUNX1. The methyltransferase SETD1B was a novel recurrently mutated gene. A novel class of variant associated with the Philadelphia translocation was detected at diagnosis in 11/46 patients (24%) comprising fusions and/or rearrangement of genes on the translocated chromosomes, with evidence of fragmentation, inversion and imperfect sequence reassembly. These were more frequent at diagnosis in patients with poor outcome: 9/27 (33%) versus 2/19 optimal responders (11%), P=.07. Thirty-nine patients were tested at BC and all had cancer gene variants, including ABL1 kinase domain mutations in 58%. However, ABL1 mutations co-occurred with other mutated cancer genes in 89% of cases, and these predated ABL1 mutations in 62% of evaluable patients. Gene fusions not associated with the Philadelphia translocation occurred in 42% of patients at BC and commonly involved fusion partners that were known cancer genes (78%). Genomic analysis revealed numerous relevant variants at diagnosis in patients with poor outcome and all patients at BC. Future refined biomarker testing of specific variants will likely provide prognostic information to facilitate a risk-adapted therapeutic approach.","abstract":"Genomic events associated with poor outcome in chronic myeloid leukemia (CML) are poorly understood. We performed whole exome sequencing, copy number variation and/or RNA-Seq for 65 patients to discover mutations at diagnosis and blast crisis (BC). Forty-six chronic phase patients with the extremes of outcome were studied at diagnosis. Cancer gene variants were detected in 15/27 patients (56%) with subsequent BC or poor outcome and in 3/19 optimal responders (16%), P=.007. Frequently mutated genes at diagnosis were ASXL1, IKZF1 and RUNX1. The methyltransferase SETD1B was a novel recurrently mutated gene. A novel class of variant associated with the Philadelphia translocation was detected at diagnosis in 11/46 patients (24%) comprising fusions and/or rearrangement of genes on the translocated chromosomes, with evidence of fragmentation, inversion and imperfect sequence reassembly. These were more frequent at diagnosis in patients with poor outcome: 9/27 (33%) versus 2/19 optimal responders (11%), P=.07. Thirty-nine patients were tested at BC and all had cancer gene variants, including ABL1 kinase domain mutations in 58%. However, ABL1 mutations co-occurred with other mutated cancer genes in 89% of cases, and these predated ABL1 mutations in 62% of evaluable patients. Gene fusions not associated with the Philadelphia translocation occurred in 42% of patients at BC and commonly involved fusion partners that were known cancer genes (78%). Genomic analysis revealed numerous relevant variants at diagnosis in patients with poor outcome and all patients at BC. Future refined biomarker testing of specific variants will likely provide prognostic information to facilitate a risk-adapted therapeutic approach.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-22T06:14:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003072","title":"SLC9A3R1 variant associated with age-related hearing loss","description":"Age-related hearing loss (ARHL) is the most common sensory impairment in the elderly affecting millions of people worldwide. To shed light on the genetics of ARHL, a large cohort of 464 Italian patients has been deeply analyzed at clinical and molecular level. \nA missense variant in SLC9A3R1 has been identified in two unrelated ARHL patients. A knock-in zebrafish model confirmed the pathogenic effect of the variant.","abstract":"Age-related hearing loss (ARHL) is the most common sensory impairment in the elderly affecting millions of people worldwide. To shed light on the genetics of ARHL, a large cohort of 464 Italian patients has been deeply analyzed at clinical and molecular level. \nA missense variant in SLC9A3R1 has been identified in two unrelated ARHL patients. A knock-in zebrafish model confirmed the pathogenic effect of the variant.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-22T09:34:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003073","title":"Ovarian cancer organoid biobank","description":"Ovarian cancer (OC) is a heterogeneous disease usually diagnosed at a late stage. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of OC are limited and hard to establish. We present a novel protocol that enables efficient derivation and long-term expansion of OC organoids. Utilizing this protocol, we have established 56 organoid lines from 32 patients, representing the spectrum of ovarian neoplasms, including non-malignant borderline tumors, as well as mucinous, clear-cell, endometrioid, low- and high-grade serous carcinomas. OC organoids recapitulate histological and genomic features of the pertinent lesion from which they were derived, illustrating intra- and inter-patient heterogeneity, and can be genetically modified.  We show that OC organoids can be used for drug screening assays and capture different tumor subtype responses to the gold standard platinum-based chemotherapy, including acquisition of chemoresistance in recurrent disease. Finally, OC organoids can be xenografted, enabling in vivo drug sensitivity assays. Taken together, this demonstrates their potential application for research and personalized medicine.","abstract":"Ovarian cancer (OC) is a heterogeneous disease usually diagnosed at a late stage. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of OC are limited and hard to establish. We present a novel protocol that enables efficient derivation and long-term expansion of OC organoids. Utilizing this protocol, we have established 56 organoid lines from 32 patients, representing the spectrum of ovarian neoplasms, including non-malignant borderline tumors, as well as mucinous, clear-cell, endometrioid, low- and high-grade serous carcinomas. OC organoids recapitulate histological and genomic features of the pertinent lesion from which they were derived, illustrating intra- and inter-patient heterogeneity, and can be genetically modified.  We show that OC organoids can be used for drug screening assays and capture different tumor subtype responses to the gold standard platinum-based chemotherapy, including acquisition of chemoresistance in recurrent disease. Finally, OC organoids can be xenografted, enabling in vivo drug sensitivity assays. Taken together, this demonstrates their potential application for research and personalized medicine.","study_type":"Other","pubmed_ids":[31011202],"external_links":null,"is_released":true,"released_date":"2018-06-22T12:47:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003074","title":"ICU_transcriptomics__Assessing_the_role_of_the_host_immune_response_in_patients_with_ventilator_associated_pneumonia","description":"The aim of the proposed project is to provide transcriptomic sequencing data analysis of cells isolated from bronchioalveolar lavage and blood samples from critically ill patients with pneumonia on an intensive care unit  in order to investigate the host contribution to disease. The lung microbiome of these patients will be analysed in parallel by deep sequencing and 16S sequencing. These data will provide important information to the development of strategies aimed at improving patient outcomes, reducing the development of antimicrobial resistance and facilitating infection control measures in hospital.\nSpecifically, the proposed work will be a proof of principle study of 100 patients. We will use transcriptomic data to define the host contribution to the symptoms of these critically ill patients diagnosed with pneumonia. The data will be correlated with cytokine/chemokine concentrations, routine microbiology analysis and pathogen genomic data from the same samples to determine the ecology of the lungs of these patients. We will look for associations between clinical features, host response and pathogen genomics in order to identify new diagnostic markers. This study should provide important information to improve the speed and accuracy of diagnosis - resulting in more targeted and successful treatment of critically ill patients in the ICU.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The aim of the proposed project is to provide transcriptomic sequencing data analysis of cells isolated from bronchioalveolar lavage and blood samples from critically ill patients with pneumonia on an intensive care unit  in order to investigate the host contribution to disease. The lung microbiome of these patients will be analysed in parallel by deep sequencing and 16S sequencing. These data will provide important information to the development of strategies aimed at improving patient outcomes, reducing the development of antimicrobial resistance and facilitating infection control measures in hospital.\nSpecifically, the proposed work will be a proof of principle study of 100 patients. We will use transcriptomic data to define the host contribution to the symptoms of these critically ill patients diagnosed with pneumonia. The data will be correlated with cytokine/chemokine concentrations, routine microbiology analysis and pathogen genomic data from the same samples to determine the ecology of the lungs of these patients. We will look for associations between clinical features, host response and pathogen genomics in order to identify new diagnostic markers. This study should provide important information to improve the speed and accuracy of diagnosis - resulting in more targeted and successful treatment of critically ill patients in the ICU.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-25T13:37:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003075","title":"Parallel Detections of Somatic Gene Mutations in Surgically Resected Tumor tissues and Matched Plasma Specimens in Early-Stages of Primary Breast Cancer","description":"We developed two panel successively, contain 68 and 136 genes respectively. Combination with ultrasound or mammography, it could be used for breast cancer early detection and avoided unnecessary surgery or other invasive detection.","abstract":"We developed two panel successively, contain 68 and 136 genes respectively. Combination with ultrasound or mammography, it could be used for breast cancer early detection and avoided unnecessary surgery or other invasive detection.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-26T03:45:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003076","title":"DNA methylomes of monozygotic twins clinically discordant for multiple sclerosis","description":"Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Although genetic susceptibility is important, a modest concordance rate for MS in monozygotic (MZ) twins suggests that interaction with other risk factors is required to develop clinical symptoms. In this study, we examined whether DNA methylation differences contribute to the discordant clinical manifestation of MS in MZ twins, and studied the impact of MS treatments on the DNA methylome. Genome-wide DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) of 45 MZ twins clinically discordant for MS were generated using the Illumina HumanMethylationEPIC array. Repetitive element methylation and selected differentially methylated positions (DMPs) were validated using targeted deep bisulfite sequencing (TDBS). In addition, we performed whole genome bisulfite sequencing (WGBS) to profile CD4+ memory T-cells of a subset of four MS discordant MZ twins. Our results show that interferon treatment causes robust DNA methylation changes and several epigenetic biomarkers for interferon treatment response were identified. However, overall the PBMC-based methylomes of the MS discordant MZ twins were highly similar, since large systematic methylation differences (&gt;5%) were absent in the data. This suggests that previously reported large methylation changes are probably caused by genetic rather than epigenetic differences. In addition, our data does not support the hypothesis that the observed maternal parent-of-origin effect in MS is due to genomic imprinting errors, and no evidence was found that copy number variations explain the discordant phenotype in these MZ twins. Although not genome-wide significant, a couple of DMPs associated with the MS phenotype were identified and successfully technically replicated using TDBS, including a differentially methylated region (DMR) in the promoter of the transmembrane protein encoding gene TMEM232. Another MS-associated DMP, located in an enhancer in the gene body of the transcription factor ZBTB16, was also associated with medium-term glucocorticoid treatment history. WGBS analysis confirmed this DMP as an epigenetic biomarker for glucocorticoid treatment. In conclusion, this epigenome-wide association study (EWAS) in genetically identical twins identified a DMR in the TMEM232 promoter as a candidate loci associated with the clinical manifestation of MS. In addition, epigenetic biomarkers for MS treatments were identified, revealing that not only short-term, but also medium-term treatment effects are detectable in immune cells, which should be taken into account in future EWAS designs.","abstract":"Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Although genetic susceptibility is important, a modest concordance rate for MS in monozygotic (MZ) twins suggests that interaction with other risk factors is required to develop clinical symptoms. In this study, we examined whether DNA methylation differences contribute to the discordant clinical manifestation of MS in MZ twins, and studied the impact of MS treatments on the DNA methylome. Genome-wide DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) of 45 MZ twins clinically discordant for MS were generated using the Illumina HumanMethylationEPIC array. Repetitive element methylation and selected differentially methylated positions (DMPs) were validated using targeted deep bisulfite sequencing (TDBS). In addition, we performed whole genome bisulfite sequencing (WGBS) to profile CD4+ memory T-cells of a subset of four MS discordant MZ twins. Our results show that interferon treatment causes robust DNA methylation changes and several epigenetic biomarkers for interferon treatment response were identified. However, overall the PBMC-based methylomes of the MS discordant MZ twins were highly similar, since large systematic methylation differences (&gt;5%) were absent in the data. This suggests that previously reported large methylation changes are probably caused by genetic rather than epigenetic differences. In addition, our data does not support the hypothesis that the observed maternal parent-of-origin effect in MS is due to genomic imprinting errors, and no evidence was found that copy number variations explain the discordant phenotype in these MZ twins. Although not genome-wide significant, a couple of DMPs associated with the MS phenotype were identified and successfully technically replicated using TDBS, including a differentially methylated region (DMR) in the promoter of the transmembrane protein encoding gene TMEM232. Another MS-associated DMP, located in an enhancer in the gene body of the transcription factor ZBTB16, was also associated with medium-term glucocorticoid treatment history. WGBS analysis confirmed this DMP as an epigenetic biomarker for glucocorticoid treatment. In conclusion, this epigenome-wide association study (EWAS) in genetically identical twins identified a DMR in the TMEM232 promoter as a candidate loci associated with the clinical manifestation of MS. In addition, epigenetic biomarkers for MS treatments were identified, revealing that not only short-term, but also medium-term treatment effects are detectable in immune cells, which should be taken into account in future EWAS designs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003077","title":"Rare and low-frequency variants in the Saguenay–Lac-Saint-Jean population","description":"The Saguenay–Lac-Saint-Jean (SLSJ) region is located in northeastern Quebec and is known for its unique demographic history and founder effect. Since founder populations are enriched with population-specific variants, we characterized the variants distribution in SLSJ and compared it with four European populations (Finnish, Sweden, United Kingdom and France), of which the Finnish population is another founder population.  Targeted sequencing of the coding and non-coding immune regulatory regions of the SLSJ asthma familial cohort and the four European populations were performed.  Rare and low-frequency coding and noncoding regulatory variants identified in the SLSJ population were then investigated for variant- and gene-level associations with asthma and allergy related-traits (eosinophil percentage, immunoglobulin (Ig)E levels and lung function).","abstract":"The Saguenay–Lac-Saint-Jean (SLSJ) region is located in northeastern Quebec and is known for its unique demographic history and founder effect. Since founder populations are enriched with population-specific variants, we characterized the variants distribution in SLSJ and compared it with four European populations (Finnish, Sweden, United Kingdom and France), of which the Finnish population is another founder population.  Targeted sequencing of the coding and non-coding immune regulatory regions of the SLSJ asthma familial cohort and the four European populations were performed.  Rare and low-frequency coding and noncoding regulatory variants identified in the SLSJ population were then investigated for variant- and gene-level associations with asthma and allergy related-traits (eosinophil percentage, immunoglobulin (Ig)E levels and lung function).","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003078","title":"Whole exome sequencing of high hyperdiploid and ETV6/RUNX1-positive pediatric acute lymphoblastic leukemia","description":"We performed whole exome sequencing of high hyperdiploid ALL cases and ETV6/RUNX1-positive ALL cases by using Nextera Rapid Capture Expanded Exome Kit to investigate the mutation profile of high hyperdiploid acute lymphoblastic leukemia cases","abstract":"We performed whole exome sequencing of high hyperdiploid ALL cases and ETV6/RUNX1-positive ALL cases by using Nextera Rapid Capture Expanded Exome Kit to investigate the mutation profile of high hyperdiploid acute lymphoblastic leukemia cases","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003079","title":"RNA sequencing of high hyperdiploid and ETV6/RUNX1-positive pediatric acute lymphoblastic leukemia","description":"We performed RNA-sequencing of high hyperdiploid and ETV6/RUNX1-positive ALL cases by using the Human Ribo-Zero rRNA Removal Kit to investigate the gene expression in high hyperdiploid ALL.","abstract":"We performed RNA-sequencing of high hyperdiploid and ETV6/RUNX1-positive ALL cases by using the Human Ribo-Zero rRNA Removal Kit to investigate the gene expression in high hyperdiploid ALL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-27T08:35:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003080","title":"Hi-C sequencing of high hyperdiploid and ETV6/RUNX1-positive pediatric acute lymphoblastic leukemia","description":"We performed RNA-seq sequencing of high hyperdiploid and ETV6/RUNX1-positive ALL-cases to investigate the chromatin architecture.","abstract":"We performed RNA-seq sequencing of high hyperdiploid and ETV6/RUNX1-positive ALL-cases to investigate the chromatin architecture.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003081","title":"Whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes.","description":"We carried out whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes. This study aimed to reveal the selective accumulation of rare variants in the coding and the UTR sequences within the genes of suicide victims. We also analysed the potential effect of STR and CNV variations, as well as the infection of the brain with neurovirulent viruses in this behavioural disorder. As a result, we have identified several candidate genes, among others three calcium channel genes that may potentially contribute to completed suicide. We also explored the potential implication of the TGF-β signalling pathway in the pathogenesis of suicidal behaviour. To our best knowledge, this is the first study that uses whole-exome sequencing for the investigation of suicide.","abstract":"We carried out whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes. This study aimed to reveal the selective accumulation of rare variants in the coding and the UTR sequences within the genes of suicide victims. We also analysed the potential effect of STR and CNV variations, as well as the infection of the brain with neurovirulent viruses in this behavioural disorder. As a result, we have identified several candidate genes, among others three calcium channel genes that may potentially contribute to completed suicide. We also explored the potential implication of the TGF-β signalling pathway in the pathogenesis of suicidal behaviour. To our best knowledge, this is the first study that uses whole-exome sequencing for the investigation of suicide.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-27T11:51:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003082","title":"PSC_in_IBD_extension","description":"Primary sclerosing cholangitis (PSC) is a T-cell mediated, chronic inflammatory condition of the biliary tree that is strongly associated with inflammatory bowel disease. Here we intend to sequence 460 RNA samples, with RNA from six different T cell populations drawn from 80 individuals. These studies will help us identify the mechanisms and genes impacted by non-coding variants associated with PSC serving to increase biological understanding of the disease and potentially identify therapeutic targets.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Primary sclerosing cholangitis (PSC) is a T-cell mediated, chronic inflammatory condition of the biliary tree that is strongly associated with inflammatory bowel disease. Here we intend to sequence 460 RNA samples, with RNA from six different T cell populations drawn from 80 individuals. These studies will help us identify the mechanisms and genes impacted by non-coding variants associated with PSC serving to increase biological understanding of the disease and potentially identify therapeutic targets.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003083","title":"HG_WGS_consanguineous_DDD_trios","description":"We would like to do 30X whole-genome sequencing on 553 individuals from 184 DDD families with South Asian ancestry and high consanguinity. In a previous analysis, we estimated that ~47% of highly autozygous Pakistani probands were likely to be explained by recessive coding variants, and ~18% by de novo coding mutations. These estimates assume that each patient’s phenotype is fully attributable to a single pathogenic variant (or pair of compound heterozygous variants). This is probably an over-simplification, particularly in the case of highly autozygous patients who have multiple rare homozygous variants, several of which may contribute to their phenotypes. DDD probands who are offspring of first cousins are only ~half as likely to have a diagnostic de novo coding mutation (the most common type of diagnostic variant in DDD), after controlling for the presence of at least one damaging biallelic coding variant. This suggests that autozygosity may be contributing to rare developmental disorders beyond a simple monogenic coding mechanism.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We would like to do 30X whole-genome sequencing on 553 individuals from 184 DDD families with South Asian ancestry and high consanguinity. In a previous analysis, we estimated that ~47% of highly autozygous Pakistani probands were likely to be explained by recessive coding variants, and ~18% by de novo coding mutations. These estimates assume that each patient’s phenotype is fully attributable to a single pathogenic variant (or pair of compound heterozygous variants). This is probably an over-simplification, particularly in the case of highly autozygous patients who have multiple rare homozygous variants, several of which may contribute to their phenotypes. DDD probands who are offspring of first cousins are only ~half as likely to have a diagnostic de novo coding mutation (the most common type of diagnostic variant in DDD), after controlling for the presence of at least one damaging biallelic coding variant. This suggests that autozygosity may be contributing to rare developmental disorders beyond a simple monogenic coding mechanism.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003084","title":"Functional_Genomics_OA_2018_DNA","description":"OA affects &gt;40% of individuals over 70y and is a leading cause of pain and loss of physical function in the UK, affecting 8.5 million patients. The molecular changes leading to the pathogenesis of OA are still poorly understood We will obtain diseased and non-diseased tissue (cartilage) following total knee replacement surgery, coupled with a blood sample. This study follows on from previous successful work with UK-based orthopaedic surgeon collaborators. We will generate genotype data and will characterise the pairs of diseased and non-diseased tissue samples in terms of transcription (RNASeq). We will apply integrative approaches to combine information across the –omics levels to characterise genes, pathways, and networks that underlie osteoarthritis progression.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"OA affects &gt;40% of individuals over 70y and is a leading cause of pain and loss of physical function in the UK, affecting 8.5 million patients. The molecular changes leading to the pathogenesis of OA are still poorly understood The samples were obtained from diseased and non-diseased tissue (cartilage) following total knee replacement surgery, coupled with a blood sample. This study follows on from previous successful work with UK-based orthopaedic surgeon collaborators.  We have generated genotype data and characterised the pairs of diseased and non-diseased tissue samples in terms of transcription (RNASeq). We applied integrative approaches to combine information across the –omics levels to characterise genes, pathways, and networks that underlie osteoarthritis progression.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003085","title":"Exome sequencing in bipolar disorder families","description":"Bipolar disorder (BD) is a major psychiatric disorder affecting around 1% of the global population. BD is characterized by recurrent manic and depressive episodes, and has an estimated heritability of around 70% Research has identified the first BD susceptibility genes. However, the underlying pathways and regulatory networks remain largely unknown. Since research has shown that the cumulative impact of common alleles with small effect appears to explain only around 25-38% of the phenotypic variance for BD, rare variants of high penetrance may also contribute to BD risk. \nThe present study investigated the role of rare, nonsynonymous, and potentially functional variants via whole exome sequencing in 15 BD cases from two large, multiply affected families from Cuba. The high prevalence of BD in these pedigrees renders them promising in terms of the identification of genetic risk variants with large effect sizes. In addition, SNP array data were used to calculate polygenic risk scores for affected and unaffected family members.\nAfter correction for multiple testing, polygenic risk scores for common, BD-associated genetic variants were not significantly higher in BD cases than in healthy relatives. \nExome sequencing identified a total of 17 rare and potentially damaging variants in 17 genes. The identified variants were shared by all investigated BD cases in the respective pedigree. The most promising variant was located in the gene SERPING1 (p.L349F), which has been reported as a genome-wide significant risk gene for schizophrenia. A further promising variant was located in CAPN2, which has been implicated in synaptic plasticity. \nThe present data suggest novel candidate genes for BD susceptibility, and may facilitate the discovery of disease-relevant pathways and regulatory networks.","abstract":"Bipolar disorder (BD) is a major psychiatric disorder affecting around 1% of the global population. BD is characterized by recurrent manic and depressive episodes, and has an estimated heritability of around 70% Research has identified the first BD susceptibility genes. However, the underlying pathways and regulatory networks remain largely unknown. Since research has shown that the cumulative impact of common alleles with small effect appears to explain only around 25-38% of the phenotypic variance for BD, rare variants of high penetrance may also contribute to BD risk. \nThe present study investigated the role of rare, nonsynonymous, and potentially functional variants via whole exome sequencing in 15 BD cases from two large, multiply affected families from Cuba. The high prevalence of BD in these pedigrees renders them promising in terms of the identification of genetic risk variants with large effect sizes. In addition, SNP array data were used to calculate polygenic risk scores for affected and unaffected family members.\nAfter correction for multiple testing, polygenic risk scores for common, BD-associated genetic variants were not significantly higher in BD cases than in healthy relatives. \nExome sequencing identified a total of 17 rare and potentially damaging variants in 17 genes. The identified variants were shared by all investigated BD cases in the respective pedigree. The most promising variant was located in the gene SERPING1 (p.L349F), which has been reported as a genome-wide significant risk gene for schizophrenia. A further promising variant was located in CAPN2, which has been implicated in synaptic plasticity. \nThe present data suggest novel candidate genes for BD susceptibility, and may facilitate the discovery of disease-relevant pathways and regulatory networks.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-28T11:12:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003086","title":"Whole genome sequencing of 46 chronic lymphocytic leukemia cases.","description":"Chronic lymphocytic leukaemia (CLL) consists of two biologically and clinically distinct subtypes defined by the abundance of somatic hypermutation (SHM) affecting the Ig variable heavy-chain locus (IgHV). The molecular mechanisms underlying these subtypes are incompletely understood. Here, we present a comprehensive whole-genome sequencing analysis of somatically acquired genetic events from 46 CLL patients, including a systematic comparison of coding and non-coding single-nucleotide variants, copy number variants and structural variants, regions of kataegis and mutation signatures between IgHVmut and IgHVunmut subtypes. We demonstrate that one-quarter of non-coding mutations in regions of kataegis outside the Ig loci are located in genes relevant to CLL. We show that non-coding mutations in ATM may negatively impact on ATM expression and find non-coding and regulatory region mutations in TCL1A, and in IgHVunmut CLL in IKZF3, SAMHD1,PAX5 and BIRC3. Finally, we show that IgHVunmut CLL is dominated by coding mutations in driver genes and an aging signature, whereas IgHVmut CLL has a high incidence of promoter and enhancer mutations caused by aberrant activation-induced cytidine deaminase activity. Taken together, our data support the hypothesis that differences in clinical outcome and biological characteristics between the two subgroups might reflect differences in mutation distribution, incidence and distinct underlying mutagenic mechanisms.","abstract":"Chronic lymphocytic leukaemia (CLL) consists of two biologically and clinically distinct subtypes defined by the abundance of somatic hypermutation (SHM) affecting the Ig variable heavy-chain locus (IgHV). The molecular mechanisms underlying these subtypes are incompletely understood. Here, we present a comprehensive whole-genome sequencing analysis of somatically acquired genetic events from 46 CLL patients, including a systematic comparison of coding and non-coding single-nucleotide variants, copy number variants and structural variants, regions of kataegis and mutation signatures between IgHVmut and IgHVunmut subtypes. We demonstrate that one-quarter of non-coding mutations in regions of kataegis outside the Ig loci are located in genes relevant to CLL. We show that non-coding mutations in ATM may negatively impact on ATM expression and find non-coding and regulatory region mutations in TCL1A, and in IgHVunmut CLL in IKZF3, SAMHD1,PAX5 and BIRC3. Finally, we show that IgHVunmut CLL is dominated by coding mutations in driver genes and an aging signature, whereas IgHVmut CLL has a high incidence of promoter and enhancer mutations caused by aberrant activation-induced cytidine deaminase activity. Taken together, our data support the hypothesis that differences in clinical outcome and biological characteristics between the two subgroups might reflect differences in mutation distribution, incidence and distinct underlying mutagenic mechanisms.","study_type":"Other","pubmed_ids":[28584254],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003087","title":"Pan Prostate Cancer Group","description":"Pan Prostate Cancer Group","abstract":"Pan Prostate Cancer Group","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003088","title":"Genomic analysis of high-risk prostate cancer.","description":"Whole genome sequencing analysis of high risk localised primary prostate cancer samples including metastatic samples was performed across 153 tumour samples with matching germline sequencing (whole blood). Samples were all fresh frozen frozen section confirmed tumour specimens and associated clinical and pathological metadata is available for these specimens.","abstract":"Whole genome sequencing analysis of high risk localised primary prostate cancer samples including metastatic samples was performed across 153 tumour samples with matching germline sequencing (whole blood). Samples were all fresh frozen frozen section confirmed tumour specimens and associated clinical and pathological metadata is available for these specimens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003089","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___GI___TPS___WGS","description":"The aim of this project is to investigate somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the study of normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to identify and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","abstract":"The aim of this project is to investigate somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the study of normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to identify and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-29T11:36:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003090","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___GI___TPS___TGS","description":"Somatic mutations (burdens and signatures) and clonal dynamics in normal human tissues from the gastrointestinal tract of individuals with tumour predisposition syndromes and DNA damage repair defects.","abstract":"The aim of this project is to investigate somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the study of normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to identify and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-06-29T11:42:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003091","title":"HSC_population_dynamics_CBD_samples","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-03T10:46:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003092","title":"Aneurysmal Subarachnoid Hemorrhage patients with or without vasospasm","description":"Cerebellar vasospasm is a severe complication of aneurysmal subarachnoid hemorrhage (aSAH) occurring for 30% of aSAH patients. To date, no biomarker of vasospasm occurrence exists and thus all aSAH patients undergo a preventive and dangerous treatment. In this study, we explored the miRNome of aSAH patients to detect potential expression differences between the patients developing a vasospasm (VSP+) or not (VSP-). The shared data include raw and normalized count miRNA data in aneurysmal subarachnoid hemorrhage patients with or without vasospasm.","abstract":"Cerebellar vasospasm is a severe complication of aneurysmal subarachnoid hemorrhage (aSAH) occurring for 30% of aSAH patients. To date, no biomarker of vasospasm occurrence exists and thus all aSAH patients undergo a preventive and dangerous treatment. In this study, we explored the miRNome of aSAH patients to detect potential expression differences between the patients developing a vasospasm (VSP+) or not (VSP-). The shared data include raw and normalized count miRNA data in aneurysmal subarachnoid hemorrhage patients with or without vasospasm.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-03T14:20:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003093","title":"Genomic and transcriptomic profiling of combined hepatocellular and intrahepatic cholangiocarcinoma reveals distinct molecular subtypes","description":"We performed genomic and transcriptomic sequencing of 133 combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC) cases, including separate, combined, and mixed subtypes.","abstract":"We performed genomic and transcriptomic sequencing of 133 combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC) cases, including separate, combined, and mixed subtypes.","study_type":"Other","pubmed_ids":[31130341],"external_links":null,"is_released":true,"released_date":"2018-07-03T15:03:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003094","title":"Bisulphite_MPN_colonies","description":"Swift kit whole genome bisulphite of MPN colonies","abstract":"Swift kit whole genome bisulphite of MPN colonies","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-04T09:17:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003095","title":"Somatic mutations in endometriosis and normal uterine endometrium","description":"To characterize the genomic features of endometriosis, we performed whole-exome sequencing for ovarian endometriotic epithelium samples obtained from subjects without concurrent gynecological cancers. Additionally, we analyzed histologically normal uterine endometrial epithelium samples obtained from subjects with benign gynecologic diseases. All the epithelium samples were isolated by laser microdissection from frozen sections.","abstract":"To characterize the genomic features of endometriosis, we performed whole-exome sequencing for ovarian endometriotic epithelium samples obtained from subjects without concurrent gynecological cancers. Additionally, we analyzed histologically normal uterine endometrial epithelium samples obtained from subjects with benign gynecologic diseases. All the epithelium samples were isolated by laser microdissection from frozen sections.","study_type":"Other","pubmed_ids":[30110635],"external_links":null,"is_released":true,"released_date":"2018-07-04T11:43:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003096","title":"Whole transcriptome RNA sequencing as comprehensive diagnostic tool for acute myeloid leukemia.","description":"BackgroundAcute myeloid leukemia (AML) is characterized by uncontrolled proliferation of malignant hematopoietic cells in the bone marrow that are arrested in differentiation. In AML pathogenesis, hematopoietic progenitor cells acquire multiple genetic aberrations often occurring in the same set of genes that ultimately lead to malignant transformation. In the WHO classification 2016, six AML classes with different prognosis are identified by chromosomal translocations measured by standard cytogenetics. All balanced translocations produce fusion genes, except for t(3;3)/inv(3;3), which lead to overexpression of MECOM/EVI1 associated with poor prognosis. For accurate risk assessment of cytogenetically normal AML, four genes need to be screened to distinguish AML with mutated NPM1 in the absence of FLT3 mutations and AML with bi-allelic CEBPA mutations, which have a favorable prognosis, and AML with RUNX1 mutations which have a poor prognosis. Recently, a full genomic classification system has been proposed by Papaemmanuil et al. (NEJM 2016). In this system, the same six classes with chromosomal translocations are identified by standard cytogenetics as well as five additional classes characterized by genetic mutations in 14 different genes. AimThe aim of the study was to investigate whether whole transcriptome RNA-sequencing (RNAseq) can be used as single technology for classification of AML. MethodA panel of 100 AML were analyzed and a bio-informatics pipeline called HAMLET (Human AML Expedited Transcriptomics) was developed in which 4 modules are integrated to detect (1) fusion genes, (2) small variants in 13 recurrently mutated genes, (3) internal tandem duplications in FLT3 (FLT3-ITD) and partial tandem duplications in KMT2A (KMT2A-PTD) and (4) overexpression of MECOM/EVI1. All mutations that were called by HAMLET were validated by diagnostic data as available for all 100 AML or targeted PCR followed by Sanger or next generation sequencing on all positive AML and at least an equal number of negative cases. Results &amp; discussionThe data showed that HAMLET accurately identified all genetic aberrations with high sensitivity and specificity. In addition, in 7 AML, fusion transcripts were detected that are not measured by standard cytogenetics including three cases that lack any class-defining lesion according to Papaemmanuil et al. Moreover, overexpression of MECOM/EVI1 was detected in two AML with inv(3) as well as in five cases without inv(3)/t(3;3), and a gene signature was measured to distinguish AML with CEBPA mutations with favorable prognosis. In conclusion, HAMLET provides a comprehensive and flexible pipeline for RNAseq analysis to retrieve all relevant information for current classification of AML as well as additional information that may improve classification in the future.","abstract":"BackgroundAcute myeloid leukemia (AML) is characterized by uncontrolled proliferation of malignant hematopoietic cells in the bone marrow that are arrested in differentiation. In AML pathogenesis, hematopoietic progenitor cells acquire multiple genetic aberrations often occurring in the same set of genes that ultimately lead to malignant transformation. In the WHO classification 2016, six AML classes with different prognosis are identified by chromosomal translocations measured by standard cytogenetics. All balanced translocations produce fusion genes, except for t(3;3)/inv(3;3), which lead to overexpression of MECOM/EVI1 associated with poor prognosis. For accurate risk assessment of cytogenetically normal AML, four genes need to be screened to distinguish AML with mutated NPM1 in the absence of FLT3 mutations and AML with bi-allelic CEBPA mutations, which have a favorable prognosis, and AML with RUNX1 mutations which have a poor prognosis. Recently, a full genomic classification system has been proposed by Papaemmanuil et al. (NEJM 2016). In this system, the same six classes with chromosomal translocations are identified by standard cytogenetics as well as five additional classes characterized by genetic mutations in 14 different genes. AimThe aim of the study was to investigate whether whole transcriptome RNA-sequencing (RNAseq) can be used as single technology for classification of AML. MethodA panel of 100 AML were analyzed and a bio-informatics pipeline called HAMLET (Human AML Expedited Transcriptomics) was developed in which 4 modules are integrated to detect (1) fusion genes, (2) small variants in 13 recurrently mutated genes, (3) internal tandem duplications in FLT3 (FLT3-ITD) and partial tandem duplications in KMT2A (KMT2A-PTD) and (4) overexpression of MECOM/EVI1. All mutations that were called by HAMLET were validated by diagnostic data as available for all 100 AML or targeted PCR followed by Sanger or next generation sequencing on all positive AML and at least an equal number of negative cases. Results &amp; discussionThe data showed that HAMLET accurately identified all genetic aberrations with high sensitivity and specificity. In addition, in 7 AML, fusion transcripts were detected that are not measured by standard cytogenetics including three cases that lack any class-defining lesion according to Papaemmanuil et al. Moreover, overexpression of MECOM/EVI1 was detected in two AML with inv(3) as well as in five cases without inv(3)/t(3;3), and a gene signature was measured to distinguish AML with CEBPA mutations with favorable prognosis. In conclusion, HAMLET provides a comprehensive and flexible pipeline for RNAseq analysis to retrieve all relevant information for current classification of AML as well as additional information that may improve classification in the future.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-05T08:38:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003097","title":"Identification_of_targets_that_can_induce_a_tolerogenic_function_in_dendritic_cells_for_the_treatment_of_immune_mediated_disease","description":"Dendritic cells (DCs) are key regulators of immune responses. DCs capture and process antigenic proteins, and present peptides from these proteins to T cells expressing antigen-specific T cell receptors. DCs also modulate the nature of the response generated through the expression of a range of cell-associated and secreted molecules. On this basis, DCs play a major role in driving the generation of polarised effector T cells subsets, such as Th1, Th2 and Th17 cells. Conversely, ‘tolerogenic’ DCs are thought to be involved in maintaining immunological tolerance via the induction of T cell unresponsiveness or apoptosis and the generation of regulatory T cells. The considerable therapeutic potential of these cells has led to a number of ongoing clinical trials transferring in vitro derived tolerogenic DCs into patients with autoimmune diseases. Hence, there is much interest in the therapeutic potential of modulating the function of DCs, including reducing the ability of these cells to activate T cells and pushing them towards a tolerogenic phenotype, in the fields of allergy, autoimmune diseases and transplant tolerance. We propose to screen for targets regulating DC phenotypes, including the tolerogenic phenotype.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"All RNA-seq will be deposited in the ENA 6 months after generation. Software used will be available on our lab website. Data will be published in a timely matter","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003098","title":"Feasibility Study to Identify the Optimal Adjuvant Combination Scheme of Ipilimumab and Nivolumab (OpACIN) in resectable stage III melanoma patients (RNA Sequencing)","description":"OpACIN is a feasibility study including 20 patients with palpable stage III melanoma that were 1:1 randomized to receive ipilimumab 3mg/kg and nivolumab 1mg/kg, either 4 courses after surgery (adjuvant arm), or 2 courses prior to surgery and 2 courses post-surgery (neoadjuvant arm). WES and RNAseq was performed on baseline biopsy material and correlated with outcome of the patients (relapse free survival). TCRseq from baseline tumor samples was used to analyse the top 100 tumor resident clones and analyse their change in PBMC comparing baseline versus week 6 of immunotherapy.","abstract":"OpACIN is a feasibility study including 20 patients with palpable stage III melanoma that were 1:1 randomized to receive ipilimumab 3mg/kg and nivolumab 1mg/kg, either 4 courses after surgery (adjuvant arm), or 2 courses prior to surgery and 2 courses post-surgery (neoadjuvant arm). WES and RNAseq was performed on baseline biopsy material and correlated with outcome of the patients (relapse free survival). TCRseq from baseline tumor samples was used to analyse the top 100 tumor resident clones and analyse their change in PBMC comparing baseline versus week 6 of immunotherapy.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003099","title":"Feasibility Study to Identify the Optimal Adjuvant Combination Scheme of Ipilimumab and Nivolumab (OpACIN) in resectable stage III melanoma patients","description":"OpACIN is a feasibility study including 20 patients with palpable stage III melanoma that were 1:1 randomized to receive ipilimumab 3mg/kg and nivolumab 1mg/kg, either 4 courses after surgery (adjuvant arm), or 2 courses prior to surgery and 2 courses post-surgery (neoadjuvant arm). WES and RNA-seq was performed on baseline biopsy material and correlated with outcome of the patients (relapse free survival). TCRseq from baseline tumor samples was used to analyse the top 100 tumor resident clones and analyse their change in PBMC comparing baseline versus week 6 of immunotherapy.","abstract":"OpACIN is a feasibility study including 20 patients with palpable stage III melanoma that were 1:1 randomized to receive ipilimumab 3mg/kg and nivolumab 1mg/kg, either 4 courses after surgery (adjuvant arm), or 2 courses prior to surgery and 2 courses post-surgery (neoadjuvant arm). WES and RNA-seq was performed on baseline biopsy material and correlated with outcome of the patients (relapse free survival). TCRseq from baseline tumor samples was used to analyse the top 100 tumor resident clones and analyse their change in PBMC comparing baseline versus week 6 of immunotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-05T16:03:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003100","title":"Somatic point mutation data from microsatellite unstable colorectal cancers","description":"Microsatellite instability (MSI) leads to accumulation of an excessive number of mutations in the genome, mostly small insertions and deletions. MSI CRCs, however, also contain more point mutations than microsatellite stable (MSS) tumors, yet they have not been as comprehensively studied. To identify candidate driver genes affected by point mutations in MSI CRC, we ranked genes based on mutation significance while correcting for replication timing and gene expression utilizing an algorithm, MutSigCV. Somatic point mutation data from the exome kit-targeted area from 24 exome sequenced sporadic MSI CRCs and respective normals, and 12 whole genome sequenced sporadic MSI CRCs and respective normals was utilized. The top 73 genes were validated in 93 additional MSI CRCs. The MutSigCV ranking identified several well-established MSI CRC driver genes, provided additional evidence for previously proposed CRC candidate genes as well as shortlisted genes that have to our knowledge not been linked to MSI CRC before. Two of these, SMARCB1 and STK38L, were also functionally scrutinized, providing evidence of a tumorigenic role – for SMARCB1 mutations in particular.","abstract":"Microsatellite instability (MSI) leads to accumulation of an excessive number of mutations in the genome, mostly small insertions and deletions. MSI CRCs, however, also contain more point mutations than microsatellite stable (MSS) tumors, yet they have not been as comprehensively studied. To identify candidate driver genes affected by point mutations in MSI CRC, we ranked genes based on mutation significance while correcting for replication timing and gene expression utilizing an algorithm, MutSigCV. Somatic point mutation data from the exome kit-targeted area from 24 exome sequenced sporadic MSI CRCs and respective normals, and 12 whole genome sequenced sporadic MSI CRCs and respective normals was utilized. The top 73 genes were validated in 93 additional MSI CRCs. The MutSigCV ranking identified several well-established MSI CRC driver genes, provided additional evidence for previously proposed CRC candidate genes as well as shortlisted genes that have to our knowledge not been linked to MSI CRC before. Two of these, SMARCB1 and STK38L, were also functionally scrutinized, providing evidence of a tumorigenic role – for SMARCB1 mutations in particular.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003101","title":"Somatic point mutation data from microsatellite unstable colorectal cancers","description":"Microsatellite instability (MSI) leads to accumulation of an excessive number of mutations in the genome, mostly small insertions and deletions. MSI CRCs, however, also contain more point mutations than microsatellite stable (MSS) tumors, yet they have not been as comprehensively studied. To identify candidate driver genes affected by point mutations in MSI CRC, we ranked genes based on mutation significance while correcting for replication timing and gene expression utilizing an algorithm, MutSigCV. Somatic point mutation data from the exome kit-targeted area from 24 exome sequenced sporadic MSI CRCs and respective normals, and 12 whole genome sequenced sporadic MSI CRCs and respective normals were utilized. The top 73 genes were validated in 93 additional MSI CRCs.","abstract":"Microsatellite instability (MSI) leads to accumulation of an excessive number of mutations in the genome, mostly small insertions and deletions. MSI CRCs, however, also contain more point mutations than microsatellite stable (MSS) tumors, yet they have not been as comprehensively studied. To identify candidate driver genes affected by point mutations in MSI CRC, we ranked genes based on mutation significance while correcting for replication timing and gene expression utilizing an algorithm, MutSigCV. Somatic point mutation data from the exome kit-targeted area from 24 exome sequenced sporadic MSI CRCs and respective normals, and 12 whole genome sequenced sporadic MSI CRCs and respective normals were utilized. The top 73 genes were validated in 93 additional MSI CRCs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-06T10:53:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003102","title":"Neoadjuvant immune checkpoint blockade in high risk resectable melanoma","description":"Preclinical studies suggest that treatment with neoadjuvant immune checkpoint blockade is associated with enhanced survival and antigen-specific T cell responses over adjuvant treatment; however, optimal regimens have not been defined. Herein, we report results from a randomized phase II study of neoadjuvant nivolumab versus combined ipilimumab with nivolumab in 23 patients with high-risk resectable melanoma (NCT02519322). RECIST overall response rates (ORR), pathologic complete response rates (pCR), treatment-related adverse events (trAEs), and immune correlates of response were assessed. Treatment with combined ipilimumab and nivolumab yielded high response rates (RECIST ORR 73%, pCR 45%) but substantial toxicity (73% grade 3 trAEs), whereas treatment with nivolumab monotherapy yielded modest responses (ORR 25%, pCR 25%) and low toxicity (8% grade 3 trAEs). Immune correlates of response were identified, demonstrating higher lymphoid infiltrates in responders to both therapies and a more clonal and diverse T cell infiltrate in responders to nivolumab monotherapy. These results are the first to describe the feasibility of neoadjuvant immune checkpoint blockade in melanoma and emphasize the need for additional studies to optimize treatment regimens and to validate putative biomarkers.","abstract":"Preclinical studies suggest that treatment with neoadjuvant immune checkpoint blockade is associated with enhanced survival and antigen-specific T cell responses over adjuvant treatment; however, optimal regimens have not been defined. Herein, we report results from a randomized phase II study of neoadjuvant nivolumab versus combined ipilimumab with nivolumab in 23 patients with high-risk resectable melanoma (NCT02519322). RECIST overall response rates (ORR), pathologic complete response rates (pCR), treatment-related adverse events (trAEs), and immune correlates of response were assessed. Treatment with combined ipilimumab and nivolumab yielded high response rates (RECIST ORR 73%, pCR 45%) but substantial toxicity (73% grade 3 trAEs), whereas treatment with nivolumab monotherapy yielded modest responses (ORR 25%, pCR 25%) and low toxicity (8% grade 3 trAEs). Immune correlates of response were identified, demonstrating higher lymphoid infiltrates in responders to both therapies and a more clonal and diverse T cell infiltrate in responders to nivolumab monotherapy. These results are the first to describe the feasibility of neoadjuvant immune checkpoint blockade in melanoma and emphasize the need for additional studies to optimize treatment regimens and to validate putative biomarkers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003103","title":"Study of the rare and low frequency variants in the Saguenay-Lac-Saint-Jean population","description":"The Saguenay–Lac-Saint-Jean (SLSJ) region is located in northeastern Quebec and is known for its unique demographic history and founder effect. Since founder populations are enriched with population-specific variants, we characterized the variants distribution in SLSJ and compared it with four European populations (Finnish, Sweden, United Kingdom and France), of which the Finnish population is another founder population.  Targeted sequencing of the coding and non-coding immune regulatory regions of the SLSJ asthma familial cohort and the four European populations were performed.  Rare and low-frequency coding and noncoding regulatory variants identified in the SLSJ population were then investigated for variant- and gene-level associations with asthma and allergy related-traits (eosinophil percentage, immunoglobulin (Ig)E levels and lung function). Our data showed that (1) rare or deleterious variants were not enriched in the two founder populations as compared to the three non-founder European populations; (2) a larger proportion of founder population-specific variants occurred with higher frequencies; and (3) low-frequency variants appeared to be more deleterious. Furthermore, a rare variant, rs1386931, located in the 3’UTR of CXCR6 and intron of FYCO1 was found to be associated with eosinophil percentage. Gene-based analyses identified NRP2, MRPL44 and SERPINE2 to be associated with various asthma and allergy related traits. Our study demonstrated the usefulness of using a founder population to identify new genes associated with asthma and allergy-related traits; thus better understand the genes and pathways implicated in pathophysiology.","abstract":"The Saguenay–Lac-Saint-Jean (SLSJ) region is located in northeastern Quebec and is known for its unique demographic history and founder effect. Since founder populations are enriched with population-specific variants, we characterized the variants distribution in SLSJ and compared it with four European populations (Finnish, Sweden, United Kingdom and France), of which the Finnish population is another founder population.  Targeted sequencing of the coding and non-coding immune regulatory regions of the SLSJ asthma familial cohort and the four European populations were performed.  Rare and low-frequency coding and noncoding regulatory variants identified in the SLSJ population were then investigated for variant- and gene-level associations with asthma and allergy related-traits (eosinophil percentage, immunoglobulin (Ig)E levels and lung function). Our data showed that (1) rare or deleterious variants were not enriched in the two founder populations as compared to the three non-founder European populations; (2) a larger proportion of founder population-specific variants occurred with higher frequencies; and (3) low-frequency variants appeared to be more deleterious. Furthermore, a rare variant, rs1386931, located in the 3’UTR of CXCR6 and intron of FYCO1 was found to be associated with eosinophil percentage. Gene-based analyses identified NRP2, MRPL44 and SERPINE2 to be associated with various asthma and allergy related traits. Our study demonstrated the usefulness of using a founder population to identify new genes associated with asthma and allergy-related traits; thus better understand the genes and pathways implicated in pathophysiology.","study_type":"Other","pubmed_ids":[30206357],"external_links":null,"is_released":true,"released_date":"2018-07-06T13:51:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003104","title":"Primary plasma cell leukemia (pPCL) samples were sequenced using the Nimblegen MedExome hybridization capture to detect translocations, copy number changes, and mutations in 20 pPCL samples and patient matched controls.","description":"Primary plasma cell leukemia (pPCL) is a rare malignancy related to multiple myeloma. Here we have assembled 20 patient samples and performed whole exome sequencing to determine the differences between multiple myeloma and pPCL.  CD138+ cells were purified from bone marrow aspirates from patients with pPCL.  Control cells were obtained from CD34+ stem cell harvests or CD3+ T cells. DNA was extracted and processed using the HyperPlus library prep kit (KAPA Biosystems) and sequenced using 75 bp paired end reads on an Illumina NextSeq500.","abstract":"Primary plasma cell leukemia (pPCL) is a rare malignancy related to multiple myeloma. Here we have assembled 20 patient samples and performed whole exome sequencing to determine the differences between multiple myeloma and pPCL.  CD138+ cells were purified from bone marrow aspirates from patients with pPCL.  Control cells were obtained from CD34+ stem cell harvests or CD3+ T cells. DNA was extracted and processed using the HyperPlus library prep kit (KAPA Biosystems) and sequenced using 75 bp paired end reads on an Illumina NextSeq500.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-06T16:32:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003105","title":"Microbial signatures and innate immune gene expression in lamina propria phagocytes of inflammatory bowel diseases patients","description":"The microbial populations associated with the lamina propria phagocyte population in CD and UC patients was examined. Specifically, the differences between phagocyte-associated microbiota (PAM) and mucosa-associated microbiota were determined.","abstract":"The microbial populations associated with the lamina propria phagocyte population in CD and UC patients was examined. Specifically, the differences between phagocyte-associated microbiota (PAM) and mucosa-associated microbiota were determined.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-07T17:47:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003106","title":"The use of cryo-EM reveals a novel fold in the tau protein in Pick’s disease","description":"Cryo-EM was used to image tau filaments extracted from the brain of a patient with behavioral-variant frontotemporal dementia. Neuropathological studies revealed abundant Pick bodies composed of 3R tau. Whole exome sequencing was performed on the patient’s DNA to confirm no mutations were present in any known candidate genes.","abstract":"Cryo-EM was used to image tau filaments extracted from the brain of a patient with behavioral-variant frontotemporal dementia. Neuropathological studies revealed abundant Pick bodies composed of 3R tau. Whole exome sequencing was performed on the patient’s DNA to confirm no mutations were present in any known candidate genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003107","title":"Genome-wide association study of carotid endarterectomy patients: AEGS1","description":"In the last decade an astonishing amount of genome–wide analysis studies (GWAS) and candidate gene studies have associated common variants to cardiovascular diseases, such as coronary artery disease and ischemic stroke. The results of these GWAS need to be validated in independent cohorts and tested for association with subphenotypes. This was the motivation to undertake GWAS experiments in the Athero-Express.","abstract":"In the last decade an astonishing amount of genome–wide analysis studies (GWAS) and candidate gene studies have associated common variants to cardiovascular diseases, such as coronary artery disease and ischemic stroke. The results of these GWAS need to be validated in independent cohorts and tested for association with subphenotypes. This was the motivation to undertake GWAS experiments in the Athero-Express.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003108","title":"Whole genome amplification and whole genome sequencing of human single cells","description":"Human single fibroblasts and T-lymphocytes were amplified using multiple annealing and looping-based amplification and multiple displacement amplification. Amplified products were next subjected to whole genome sequencing with the goal of performing a genetic variant analysis.","abstract":"Human single fibroblasts and T-lymphocytes were amplified using multiple annealing and looping-based amplification and multiple displacement amplification. Amplified products were next subjected to whole genome sequencing with the goal of performing a genetic variant analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-10T12:38:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003109","title":"Monogenic IBD","description":"Monogenic disorders associated with IBD-like intestinal inflammation are a group of severe and rare conditions which are raise difficult diagnostic and therapeutic issues. Using whole-exome sequencing, we uncovered compound missense mutations in intestinal phosphatase alkaline, ALPI, in two unrelated patients.","abstract":"Monogenic disorders associated with IBD-like intestinal inflammation are a group of severe and rare conditions which are raise difficult diagnostic and therapeutic issues. Using whole-exome sequencing, we uncovered compound missense mutations in intestinal phosphatase alkaline, ALPI, in two unrelated patients.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003110","title":"Circulating cell-free DNA analysis in Small Cell Lung Cancer","description":"Small cell lung cancer (SCLC) accounts for ~250,000 deaths worldwide each year. Acquisition of adequate tumour biopsies is challenging and liquid biopsies present the best option for patient stratification and response monitoring. We present genome-wide and targeted plasma DNA sequencing data that identifies tumour related changes in 91% of limited (LS-SCLC) and 100% of extensive stage (ES-SCLC) patients. Parallel analysis of circulating tumour cells (CTCs, by CellSearch) based on ≥ 1 CTC/7.5ml blood increased tumour detection frequencies to 98% patients (95% for LS-SCLC) where CTC count and plasma DNA readouts correlated with disease stage and overall survival (OS). Targeted plasma DNA sequencing identified potential therapeutic targets in &gt;50% of patients. This approach will support trials of targeted therapies where improved patients outcomes are urgently required.","abstract":"Small cell lung cancer (SCLC) accounts for ~250,000 deaths worldwide each year. Acquisition of adequate tumour biopsies is challenging and liquid biopsies present the best option for patient stratification and response monitoring. We present genome-wide and targeted plasma DNA sequencing data that identifies tumour related changes in 91% of limited (LS-SCLC) and 100% of extensive stage (ES-SCLC) patients. Parallel analysis of circulating tumour cells (CTCs, by CellSearch) based on ≥ 1 CTC/7.5ml blood increased tumour detection frequencies to 98% patients (95% for LS-SCLC) where CTC count and plasma DNA readouts correlated with disease stage and overall survival (OS). Targeted plasma DNA sequencing identified potential therapeutic targets in &gt;50% of patients. This approach will support trials of targeted therapies where improved patients outcomes are urgently required.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-10T15:45:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003111","title":"A genetic study of a patient with familial MPN and dup chr 14q32","description":"A patient from a North American family with an autosomal dominant predisposition to myeloid neoplasms and a 1.8Mb duplication of chromosome 14q32 not involving GSKIP and ATG2B.","abstract":"A patient from a North American family with an autosomal dominant predisposition to myeloid neoplasms and a 1.8Mb duplication of chromosome 14q32 not involving GSKIP and ATG2B.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003112","title":"Whole_genome_sequencing_of_in_vitro_colonies","description":"In this study we will perform whole genome sequencing on in vitro colonies. Colonies of various sizes (100-300 cells) will be collected for somatic mutation analysis.","abstract":"In this study we will perform whole genome sequencing on in vitro colonies. Colonies of various sizes (100-300 cells) will be collected for somatic mutation analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-11T11:40:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003113","title":"Frequent mutation of the FOXA1 untranslated region in prostate cancer","description":"We sequenced the coding and untranslated regions of 72 prostate cancer driver genes in 712 plasma cell free DNA samples from 428 men with metastatic prostate cancer, in an effort to understand the role of untranslated region mutations in late stage prostate cancer.","abstract":"We sequenced the coding and untranslated regions of 72 prostate cancer driver genes in 712 plasma cell free DNA samples from 428 men with metastatic prostate cancer, in an effort to understand the role of untranslated region mutations in late stage prostate cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-12T15:19:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003114","title":"Reconstruction of human terminal erythroid differentiation cell at single cell level","description":"Terminal erythroid differentiation cells(GYPA+ cells) were isolated from neonate cord blood(CB) and adult bowe marrow(BM). single cell transcriptome sequencing library was constructed by 10X genomics system and sequenced by Illumina X ten platform. Sequencing data was analyzed to profile dynamic expression genes and centre regulators during terminal erythroid differentiation stage within CB and BM.","abstract":"Terminal erythroid differentiation cells(GYPA+ cells) were isolated from neonate cord blood(CB) and adult bowe marrow(BM). single cell transcriptome sequencing library was constructed by 10X genomics system and sequenced by Illumina X ten platform. Sequencing data was analyzed to profile dynamic expression genes and centre regulators during terminal erythroid differentiation stage within CB and BM.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-13T07:57:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003115","title":"Organoid Models of Human Liver Cancers Derived from Tumor Needle Biopsies","description":null,"abstract":"Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the second cause of cancer-related mortality worldwide. HCC mainly arises in livers with pre-existing underlying diseases including viral hepatitis, alcoholic liver disease and nonalcoholic steatohepatitis. The multikinase inhibitor Sorafenib is the only drug available for the treatment of advanced HCC. However, due to the different backgrounds and the resulting heterogeneity of tumors, its efficacy greatly varies between patients and is further limited due to adverse effects and the development of drug resistance. Current in vitro models to study HCC based on pre-existing cancer cell lines fail in recapitulating key features such as tumor architecture, cellular heterogeneity and cell-cell interactions. In this study we report the generation of long-term three-dimensional organoid cultures from tumor biopsies of HCC patients with different etiologies and tumor stages. We demonstrate that HCC organoids retain the morphology and histological grading of the primary tumor as well as the expression pattern of HCC tumor markers. Moreover, whole exome sequencing analyses demonstrated that HCC organoids preserve the genetic heterogeneity present in their original tumors. Finally, in proof-of-principle studies we show that liver cancer organoids can be used to test sensitivity to Sorafenib. In conclusion, organoid models can be derived from needle biopsies of liver cancers, preserve the original tumor characteristics and provide a novel tool for developing tailored therapies urgently needed for a frequent malignancy with limited treatment options.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-15T10:36:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003116","title":"DNA-seq from plasma of 14 liver transplantation patients","description":"We performed DNA sequencing on the plasma of 14 liver transplantation patients to study the liver DNA in the plasma.","abstract":"We performed DNA sequencing on the plasma of 14 liver transplantation patients to study the liver DNA in the plasma.","study_type":"Other","pubmed_ids":[30373822],"external_links":null,"is_released":true,"released_date":"2018-07-16T09:06:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003117","title":"BS-seq in plasma of CRC patients","description":"We performed whole genome bisulfite sequencing of plasma DNA in 11 colorectal cancer patients to study the colonic DNA in plasma.","abstract":"We performed whole genome bisulfite sequencing of plasma DNA in 11 colorectal cancer patients to study the colonic DNA in plasma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-16T09:09:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003118","title":"Histone acetylome-wide association study on tuberculosis infection","description":"Epigenetic mechanisms are thought to play an important role in the pathogenesis of infectious diseases. Here, we describe the first histone acetylome-wide association study (HAWAS) of an infectious disease, based on genome-wide H3K27 acetylation profiling of peripheral granulocytes and monocytes from subjects with active Mycobacterium tuberculosis (Mtb) infection and healthy controls (135 ChIP-seq datasets).","abstract":"Epigenetic mechanisms are thought to play an important role in the pathogenesis of infectious diseases. Here, we describe the first histone acetylome-wide association study (HAWAS) of an infectious disease, based on genome-wide H3K27 acetylation profiling of peripheral granulocytes and monocytes from subjects with active Mycobacterium tuberculosis (Mtb) infection and healthy controls (135 ChIP-seq datasets).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-17T12:46:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003119","title":"Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers","description":"Infiltration of human cancers by T cells is generally interpreted as a sign of immune recognition, and there is a growing effort to reactivate dysfunctional T cells at such tumor sites. However, these efforts only have value if the intratumoral T cell receptor (TCR) repertoire of such cells is intrinsically tumor-reactive, and this has not been established in an unbiased manner for most human cancers. To address this issue, we analyzed the intrinsic tumor-reactivity of the intratumoral TCR repertoire of CD8+ T cells in ovarian and colorectal cancer – two tumor types for which T cell infiltrates form a positive prognostic marker. Data obtained demonstrate that a capacity to recognize autologous tumor is limited to approximately 10% of intratumoral CD8+ T cells. Furthermore, in two out of four patient samples tested, no tumor-reactive TCRs were identified, despite infiltration of their tumors by T cells. These data indicate that the intrinsic capacity of intratumoral T cells to recognize adjacent tumor tissue can be rare and variable, and suggest that clinical efforts to reactivate intratumoral T cells will benefit from approaches that simultaneously increase the quality of the intratumoral TCR repertoire.","abstract":"Infiltration of human cancers by T cells is generally interpreted as a sign of immune recognition, and there is a growing effort to reactivate dysfunctional T cells at such tumor sites. However, these efforts only have value if the intratumoral T cell receptor (TCR) repertoire of such cells is intrinsically tumor-reactive, and this has not been established in an unbiased manner for most human cancers. To address this issue, we analyzed the intrinsic tumor-reactivity of the intratumoral TCR repertoire of CD8+ T cells in ovarian and colorectal cancer – two tumor types for which T cell infiltrates form a positive prognostic marker. Data obtained demonstrate that a capacity to recognize autologous tumor is limited to approximately 10% of intratumoral CD8+ T cells. Furthermore, in two out of four patient samples tested, no tumor-reactive TCRs were identified, despite infiltration of their tumors by T cells. These data indicate that the intrinsic capacity of intratumoral T cells to recognize adjacent tumor tissue can be rare and variable, and suggest that clinical efforts to reactivate intratumoral T cells will benefit from approaches that simultaneously increase the quality of the intratumoral TCR repertoire.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-17T15:21:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003120","title":"Whole-genome sequencing of six populations from China","description":"Whole-genome sequencing of 81 samples from six populations in China not present in the HGDP-CEPH panel, using Illumina-HTP NovaSeq 6000. These data are part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/.","abstract":"Whole-genome sequencing of 81 samples from six populations in China not present in the HGDP-CEPH panel, using Illumina-HTP NovaSeq 6000. These data are part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003121","title":"Resolving the Full Spectrum of Human Genome Variation using Linked-Reads","description":"Large-scale population based analyses coupled with advances in technology have demonstrated that the human genome is more diverse than originally thought. Standard short-read approaches, used primarily due to accuracy, throughput and costs, fail to give a complete picture of a genome. They struggle to identify large, balanced structural events, cannot access repetitive regions of the genome and fail to resolve the human genome into its two haplotypes. Here we describe an approach that retains long range information while harnessing the power of short reads. Starting from only 1ng of DNA, we produce barcoded short read libraries. The use of novel informatic approaches allows for the barcoded short reads to be associated with the long molecules of origin producing a novel datatype known as 'Linked-Reads'. This approach allows for simultaneous detection of small and large variants from a single Linked-Read library. We have previously demonstrated the utility of whole genome Linked-Reads (lrWGS) for performing diploid, de novo assembly of individual genomes. In this manuscript, we show the utility of reference based analysis using a single Linked-Read library for full spectrum genome analysis. We demonstrate the ability of Linked-Reads to reconstruct megabase scale haplotypes and to recover parts of the genome that are typically inaccessible to short reads, including phenotypically important genes such as STRC, SMN1 and SMN2. We demonstrate the ability of both lrWGS and Linked-Read Whole Exome Sequencing (lrWES) to identify complex structural variations, including balanced events, single exon deletions, and single exon duplications. The data presented here show that Linked-Reads provide a scalable approach for comprehensive genome analysis that is not possible using short reads alone.","abstract":"Large-scale population based analyses coupled with advances in technology have demonstrated that the human genome is more diverse than originally thought. Standard short-read approaches, used primarily due to accuracy, throughput and costs, fail to give a complete picture of a genome. They struggle to identify large, balanced structural events, cannot access repetitive regions of the genome and fail to resolve the human genome into its two haplotypes. Here we describe an approach that retains long range information while harnessing the power of short reads. Starting from only 1ng of DNA, we produce barcoded short read libraries. The use of novel informatic approaches allows for the barcoded short reads to be associated with the long molecules of origin producing a novel datatype known as 'Linked-Reads'. This approach allows for simultaneous detection of small and large variants from a single Linked-Read library. We have previously demonstrated the utility of whole genome Linked-Reads (lrWGS) for performing diploid, de novo assembly of individual genomes. In this manuscript, we show the utility of reference based analysis using a single Linked-Read library for full spectrum genome analysis. We demonstrate the ability of Linked-Reads to reconstruct megabase scale haplotypes and to recover parts of the genome that are typically inaccessible to short reads, including phenotypically important genes such as STRC, SMN1 and SMN2. We demonstrate the ability of both lrWGS and Linked-Read Whole Exome Sequencing (lrWES) to identify complex structural variations, including balanced events, single exon deletions, and single exon duplications. The data presented here show that Linked-Reads provide a scalable approach for comprehensive genome analysis that is not possible using short reads alone.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-18T23:46:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003122","title":"Oesophageal_Adenocarcinoma_Organoid_Hi_C","description":"Hi-C Sequencing of 6 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical rescetion of the tumour. All model derivations took place with the CGaP facility in Sanger.  This Hi-C data will be combined with other sequencing data in order to generate accurate reference cancer genomes.","abstract":"There is complex interplay between underlying genetic sequence and epigenetic factors, however this interplay is still illusive. Massively reconstructed cancer genomes can be used in order to better understand this relationship. Six oesophageal adenocarcinoma organoids will be sequenced using long read sequencing technologies and will be profiled for a range of epigenetic marks. Combination of genetic and epigenetic data will allow the thorough characterisation of reference cancer genomes and will provide novel insights into mechanisms of gene regulation.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-19T14:32:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003123","title":"Heritable pulmonary arterial hypertension in a large Iberian family","description":"Data from a study of a large Iberian family (n=65 subjects, 5 generations) affected by pulmonary arterial hypertension (PAH) and segregating with the BMPR2 missense mutation p.Arg491Gln (rs137852749, c.1472G&gt;A). PAH is a rare disease characterized by an abnormal rise in mean pulmonary arterial pressure (&gt; or equal to 25 mmHg at rest), which, in turn, leads to a progressive increase in pulmonary vascular resistance and ultimately to death, due to right ventricular failure. Heritable PAH has an overall prevalence below 1 case per million adults and is defined by either the presence of a known genetic defect linked to the disease or a positive family history. Heritable PAH is inherited as an autosomal dominant disease. However, not all BMPR2 mutation carriers develop the disease, highlighting the presence of reduced penetrance. In this family, there are 22 mutation carriers from which 8 were diagnosed with heritable PAH and the other 14 were healthy at the time of examination.","abstract":"Data from a study of a large Iberian family (n=65 subjects, 5 generations) affected by pulmonary arterial hypertension (PAH) and segregating with the BMPR2 missense mutation p.Arg491Gln (rs137852749, c.1472G&gt;A). PAH is a rare disease characterized by an abnormal rise in mean pulmonary arterial pressure (&gt; or equal to 25 mmHg at rest), which, in turn, leads to a progressive increase in pulmonary vascular resistance and ultimately to death, due to right ventricular failure. Heritable PAH has an overall prevalence below 1 case per million adults and is defined by either the presence of a known genetic defect linked to the disease or a positive family history. Heritable PAH is inherited as an autosomal dominant disease. However, not all BMPR2 mutation carriers develop the disease, highlighting the presence of reduced penetrance. In this family, there are 22 mutation carriers from which 8 were diagnosed with heritable PAH and the other 14 were healthy at the time of examination.","study_type":"Other","pubmed_ids":[30894412],"external_links":null,"is_released":true,"released_date":"2018-07-19T15:14:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003124","title":"Oesophageal_Adenocarcinoma_Organoid_Bisulfite_Sequencing","description":"Bisulfite Sequencing of 6 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical resection of the tumour. All model derivations took place with the CGaP facility in Sanger.  This bisulfite sequencing data will be combined with other genetic and epigenetic sequencing data in order to gain a better understanding of the interplay between genetic and epigenetic modifications.","abstract":"There is complex interplay between underlying genetic sequence and epigenetic factors, however this interplay is still illusive. Massively reconstructed cancer genomes can be used in order to better understand this relationship. Six oesophageal adenocarcinoma organoids will be sequenced using long read sequencing technologies and will be profiled for a range of epigenetic marks. Combination of genetic and epigenetic data will allow the thorough characterisation of reference cancer genomes and will provide novel insights into mechanisms of gene regulation.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003125","title":"Lymphocyte_10X_RNAseq","description":"Performing single cell RNAseq using the 10X genomics 5 prime library and VDJ enrichment kits, on lymphocytes sorted from a healthy individual.","abstract":"Performing single cell RNAseq using the 10X genomics 5 prime library and VDJ enrichment kits, on lymphocytes sorted from a healthy individual.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003126","title":"Understanding human fetal pancreas development using subpopulation sorting and RNA sequencing","description":"To decipher the populations of cells present in the human fetal pancreas and their lineage relationships, we developed strategies to isolate pancreatic progenitors, endocrine progenitors and endocrine cells. Transcriptome analysis of the individual populationsrevealed a large degree of conservation among vertebrates in the drivers of gene expression changes occurring at different steps of differentiation, althoughnotably, sometimes, different members of the same gene family are expressed. The transcriptome analysis establishes a resource to identify novel genes and pathways involved in human pancreas development. Single cell profiling further captured intermediate stages ofdifferentiation and enabled us to decipher the sequence of transcriptional events occurring during human endocrine differentiation. Furthermore, we evaluate how well individual pancreatic cells derived in vitro from human pluripotent stem cells mirror the natural processoccurring in human fetuses. This comparison uncovers a few differences at the progenitor steps, a convergence at the steps of endocrine induction and the current inability to fully resolve endocrine cell subtypes in vitro.","abstract":"To decipher the populations of cells present in the human fetal pancreas and their lineage relationships, we developed strategies to isolate pancreatic progenitors, endocrine progenitors and endocrine cells. Transcriptome analysis of the individual populationsrevealed a large degree of conservation among vertebrates in the drivers of gene expression changes occurring at different steps of differentiation, althoughnotably, sometimes, different members of the same gene family are expressed. The transcriptome analysis establishes a resource to identify novel genes and pathways involved in human pancreas development. Single cell profiling further captured intermediate stages ofdifferentiation and enabled us to decipher the sequence of transcriptional events occurring during human endocrine differentiation. Furthermore, we evaluate how well individual pancreatic cells derived in vitro from human pluripotent stem cells mirror the natural processoccurring in human fetuses. This comparison uncovers a few differences at the progenitor steps, a convergence at the steps of endocrine induction and the current inability to fully resolve endocrine cell subtypes in vitro.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003127","title":"Understanding human fetal pancreas development using subpopulation sorting and RNA sequencing","description":"To decipher the populations of cells present in the human fetal pancreas and their lineage relationships, we developed strategies to isolate pancreatic progenitors, endocrine progenitors and endocrine cells. Transcriptome analysis of the individual populationsrevealed a large degree of conservation among vertebrates in the drivers of gene expression changes occurring at different steps of differentiation, althoughnotably, sometimes, different members of the same gene family are expressed. The transcriptome analysis establishes a resource to identify novel genes and pathways involved in human pancreas development. Single cell profiling further captured intermediate stages ofdifferentiation and enabled us to decipher the sequence of transcriptional events occurring during human endocrine differentiation. Furthermore, we evaluate how well individual pancreatic cells derived in vitro from human pluripotent stem cells mirror the natural processoccurring in human fetuses. This comparison uncovers a few differences at the progenitor steps, a convergence at the steps of endocrine induction and the current inability to fully resolve endocrine cell subtypes in vitro.","abstract":"To decipher the populations of cells present in the human fetal pancreas and their lineage relationships, we developed strategies to isolate pancreatic progenitors, endocrine progenitors and endocrine cells. Transcriptome analysis of the individual populationsrevealed a large degree of conservation among vertebrates in the drivers of gene expression changes occurring at different steps of differentiation, althoughnotably, sometimes, different members of the same gene family are expressed. The transcriptome analysis establishes a resource to identify novel genes and pathways involved in human pancreas development. Single cell profiling further captured intermediate stages ofdifferentiation and enabled us to decipher the sequence of transcriptional events occurring during human endocrine differentiation. Furthermore, we evaluate how well individual pancreatic cells derived in vitro from human pluripotent stem cells mirror the natural processoccurring in human fetuses. This comparison uncovers a few differences at the progenitor steps, a convergence at the steps of endocrine induction and the current inability to fully resolve endocrine cell subtypes in vitro.","study_type":"Other","pubmed_ids":[30042179],"external_links":null,"is_released":true,"released_date":"2018-07-20T18:08:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003128","title":"Circular RNA characterization in functionally distinct brain regions","description":"Circular RNAs (circRNAs) represent a class of endogenous, non-coding RNAs that are formed when exons back splice to each other and that are both highly conserved and pervasively expressed in the mammalian brain. The goal of this study was thus to systematically identify and characterize circRNA expression and as well as to evaluate the predicted impact on regulatory networks in five functionally distinct cortical regions of healthy aged human brain - cerebellum (BC), inferior parietal lobe (IPL), middle temporal gyrus (MTG), occipital cortex (OC) and superior frontal gyrus (SGF).","abstract":"Circular RNAs (circRNAs) represent a class of endogenous, non-coding RNAs that are formed when exons back splice to each other and that are both highly conserved and pervasively expressed in the mammalian brain. The goal of this study was thus to systematically identify and characterize circRNA expression and as well as to evaluate the predicted impact on regulatory networks in five functionally distinct cortical regions of healthy aged human brain - cerebellum (BC), inferior parietal lobe (IPL), middle temporal gyrus (MTG), occipital cortex (OC) and superior frontal gyrus (SGF).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-23T00:48:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003129","title":"Single_cell_of_CSF_samples_from_depression","description":"lmmune cells from CSF will be sorted into samples are to be used plates with lysis buffer. Single cells libraries will be generated and sequenced\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"lmmune cells from CSF will be sorted into\nsamples are to be used plates with lysis buffer. Single cells libraries\nwill be generated and sequenced","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003130","title":"Exome sequencing of advanced hepatocellular carcinoma","description":"The aim of our project is to decipher the genomic of advanced hepatocellular carcinoma using whole exome sequencing. To this purpose, we aim to compare genetic landscape of advanced hepatocellular carcinoma with early tumor in order to understand the mechanisms of tumor progression. This work will also help to identify new therapeutic targets potentially useful to treat patients at advanced stage. This study contain whole exome sequencing aligned reads for 41 tumor with matched normal samples","abstract":"The aim of our project is to decipher the genomic of advanced hepatocellular carcinoma using whole exome sequencing. To this purpose, we aim to compare genetic landscape of advanced hepatocellular carcinoma with early tumor in order to understand the mechanisms of tumor progression. This work will also help to identify new therapeutic targets potentially useful to treat patients at advanced stage. This study contain whole exome sequencing aligned reads for 41 tumor with matched normal samples","study_type":"Other","pubmed_ids":[31206197],"external_links":null,"is_released":true,"released_date":"2018-07-25T16:54:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003131","title":"WES+WGS OSCCs Boot et al. 2018","description":"WES of 18 OSCCs with paired normal (blood)WGS of TC1 and 62074759 (exomes previously published in Vettore et al. genome medicine 2015)","abstract":"WES of 18 OSCCs with paired normal (blood)WGS of TC1 and 62074759 (exomes previously published in Vettore et al. genome medicine 2015)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-27T03:55:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003132","title":"Epigenomic_profiling_in_DD_2","description":"Using 428 cases and 45 controls we will investigate whether we can identify characteristic DNA methylation signatures for specific chromatin related developmental disorders in accessible tissues. In our pilto study analysis of those data has revealed that 13 of these disorders have characteristic blood methylation signatures likely to be strong enough to allow good discrimination between pathogenic and benign variants. Here we will: - validate the methylation signature in these 13 disorders, determine the diagnostic utility of methylation biomarkers in 11 disorders , explore, in 6 disorders, the use of saliva DNA for detecting a disorder-specific methylation profile where the blood methylation signature is strong,  determine in, 4 disorders, whether apparent protein truncating variants inherited from an unaffected parent demonstrate the same methylation signature, and in 2 disorders, investigation of whether the blood methylation signature is of likely pathophysiological relevance or is a non-causal. \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Using 428 cases and 45 controls we will investigate whether we can identify characteristic DNA methylation signatures for specific chromatin related developmental disorders in accessible tissues. In our pilto study analysis of those data has revealed that 13 of these disorders have characteristic blood methylation signatures likely to be strong enough to allow good discrimination between pathogenic and benign variants. Here we will: - validate the methylation signature in these 13 disorders, determine the diagnostic utility of methylation biomarkers in 11 disorders , explore, in 6 disorders, the use of saliva DNA for detecting a disorder-specific methylation profile where the blood methylation signature is strong,  determine in, 4 disorders, whether apparent protein truncating variants inherited from an unaffected parent demonstrate the same methylation signature, and in 2 disorders, investigation of whether the blood methylation signature is of likely pathophysiological relevance or is a non-causal.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003133","title":"Response to Olaparib in a PALB2 Germline Mutated Prostate Cancer and Genetic Events Associated with Resistance (H021)","description":"We present a case report of a 43-year-old patient with locally advanced and castration-refractory prostate adenocarcinoma. Molecular analysis of the primary tumor and a metastasis revealed a PALB2 frameshift deletion in the germline and other indications of deficiencies in DNA repair via homologous recombination. This prompted a molecularly informed tumor board recommendation of poly(ADP-ribose) polymerase (PARP) inhibitor treatment with or without platinum-based chemotherapy, which resulted in substantial improvement of clinical symptoms.","abstract":"We present a case report of a 43-year-old patient with locally advanced and castration-refractory prostate adenocarcinoma. Molecular analysis of the primary tumor and a metastasis revealed a PALB2 frameshift deletion in the germline and other indications of deficiencies in DNA repair via homologous recombination. This prompted a molecularly informed tumor board recommendation of poly(ADP-ribose) polymerase (PARP) inhibitor treatment with or without platinum-based chemotherapy, which resulted in substantial improvement of clinical symptoms.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003134","title":"A comparison of copy-number signatures in archival and relapsed high-grade serous ovarian cancer","description":"This study contains the data underlying our approach for comparison of copy-number signature exposures in archival and relapsed high-grade serous ovarian cancer samples. The samples studied are part of the BriTROC-1 consortium, a national study into relapsed high-grade serous ovarian cancer. The dataset consists of shallow-whole genome sequencing with matched tagged-amplicon sequencing of TP53.","abstract":"This study contains the data underlying our approach for comparison of copy-number signature exposures in archival and relapsed high-grade serous ovarian cancer samples. The samples studied are part of the BriTROC-1 consortium, a national study into relapsed high-grade serous ovarian cancer. The dataset consists of shallow-whole genome sequencing with matched tagged-amplicon sequencing of TP53.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003135","title":"Dissecting Chemoresistance in cALL using PDX models","description":"This study contains bulk and single cell RNA sequencing of several PDX mice containing cells from one cALL patient. These cells have been subjected to different treatment regimens.","abstract":"This study contains bulk and single cell RNA sequencing of several PDX mice containing cells from one cALL patient. These cells have been subjected to different treatment regimens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003136","title":"Open_Targets_020_Epigenomes_of_Cell_Lines","description":"There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard &amp; complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target &amp; compound studies to primary human cells and tissues from both healthy volunteers &amp; patients.\nThe CTTV020 epigenomes of cell line project aims to generate epigenetic and transcriptomic profiles of cell lines and compare these with existing and newly generated reference data sets from human tissue and cell types. The aim is to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients. \nMultiple cell types commonly used within research have been grouped according to biology. Examples include erythroid, lung epithelial, hepatocyte cell types and immortalised models of monocyte / macrophage biology.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard &amp; complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target &amp; compound studies to primary human cells and tissues from both healthy volunteers &amp; patients.\nThe CTTV020 epigenomes of cell line project aims to generate epigenetic and transcriptomic profiles of cell lines and compare these with existing and newly generated reference data sets from human tissue and cell types. The aim is to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients. \nMultiple cell types commonly used within research have been grouped according to biology. Examples include erythroid, lung epithelial, hepatocyte cell types and immortalised models of monocyte / macrophage biology.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-31T08:44:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003137","title":"Open_Targets_020_Epigenomes_of_Cell_Lines","description":"There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard &amp; complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target &amp; compound studies to primary human cells and tissues from both healthy volunteers &amp; patients.\nThe CTTV020 epigenomes of cell line project aims to generate epigenetic and transcriptomic profiles of cell lines and compare these with existing and newly generated reference data sets from human tissue and cell types. The aim is to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients. \nMultiple cell types commonly used within research have been grouped according to biology. Examples include erythroid, lung epithelial, hepatocyte cell types and immortalised models of monocyte / macrophage biology.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard &amp; complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target &amp; compound studies to primary human cells and tissues from both healthy volunteers &amp; patients.\nThe CTTV020 epigenomes of cell line project aims to generate epigenetic and transcriptomic profiles of cell lines and compare these with existing and newly generated reference data sets from human tissue and cell types. The aim is to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients. \nMultiple cell types commonly used within research have been grouped according to biology. Examples include erythroid, lung epithelial, hepatocyte cell types and immortalised models of monocyte / macrophage biology.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-31T08:51:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003138","title":"Open_Targets_020_Epigenomes_of_Cell_Lines","description":"There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard &amp; complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target &amp; compound studies to primary human cells and tissues from both healthy volunteers &amp; patients.\nThe CTTV020 epigenomes of cell line project aims to generate epigenetic and transcriptomic profiles of cell lines and compare these with existing and newly generated reference data sets from human tissue and cell types. The aim is to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients. \nMultiple cell types commonly used within research have been grouped according to biology. Examples include erythroid, lung epithelial, hepatocyte cell types and immortalised models of monocyte / macrophage biology.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard &amp; complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target &amp; compound studies to primary human cells and tissues from both healthy volunteers &amp; patients.\nThe CTTV020 epigenomes of cell line project aims to generate epigenetic and transcriptomic profiles of cell lines and compare these with existing and newly generated reference data sets from human tissue and cell types. The aim is to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients. \nMultiple cell types commonly used within research have been grouped according to biology. Examples include erythroid, lung epithelial, hepatocyte cell types and immortalised models of monocyte / macrophage biology.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-31T09:01:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003139","title":"Open_Targets_020_Epigenomes_of_Cell_Lines","description":"There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard &amp; complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target &amp; compound studies to primary human cells and tissues from both healthy volunteers &amp; patients.\nThe CTTV020 epigenomes of cell line project aims to generate epigenetic and transcriptomic profiles of cell lines and compare these with existing and newly generated reference data sets from human tissue and cell types. The aim is to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients. \nMultiple cell types commonly used within research have been grouped according to biology. Examples include erythroid, lung epithelial, hepatocyte cell types and immortalised models of monocyte / macrophage biology.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard &amp; complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target &amp; compound studies to primary human cells and tissues from both healthy volunteers &amp; patients.\nThe CTTV020 epigenomes of cell line project aims to generate epigenetic and transcriptomic profiles of cell lines and compare these with existing and newly generated reference data sets from human tissue and cell types. The aim is to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients. \nMultiple cell types commonly used within research have been grouped according to biology. Examples include erythroid, lung epithelial, hepatocyte cell types and immortalised models of monocyte / macrophage biology.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-31T09:06:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003140","title":"Automated image-based profiling of complex drug induced phenotypes in patient-derived organoids","description":"We established a platform for high-throughput confocal fluorescence microscopy and automated image analysis to perform large-scale drug response profiling with patient derived organoids (PDOs). Using PDO lines newly established from colorectal cancer patients with a standardized workflow, we performed chemical perturbations with more than 500 experimental and clinically used compounds. Subsequently, we captured approx. six million images by confocal microscopy. To analyze drug-induced PDO re-organization on a single organoid level we developed SCOPE, a software framework for automated PDO high-throughput image analysis. We observed a rich variety of divergent and reoccurring compound induced phenotypes in organoids. Perturbation of cellular processes, including signaling by MEK, GSK3β, cyclin dependent kinases (CDKs) and others, led to recurring and distinct architectural changes. Highlighting the clinical relevance, PDO viability was heterogeneous after perturbation with anticancer drugs and matched clinical response of corresponding colorectal cancer patients. Our work opens new avenues for image-based profiling for accelerated drug discovery and clinical decision-making.","abstract":"We established a platform for high-throughput confocal fluorescence microscopy and automated image analysis to perform large-scale drug response profiling with patient derived organoids (PDOs). Using PDO lines newly established from colorectal cancer patients with a standardized workflow, we performed chemical perturbations with more than 500 experimental and clinically used compounds. Subsequently, we captured approx. six million images by confocal microscopy. To analyze drug-induced PDO re-organization on a single organoid level we developed SCOPE, a software framework for automated PDO high-throughput image analysis. We observed a rich variety of divergent and reoccurring compound induced phenotypes in organoids. Perturbation of cellular processes, including signaling by MEK, GSK3β, cyclin dependent kinases (CDKs) and others, led to recurring and distinct architectural changes. Highlighting the clinical relevance, PDO viability was heterogeneous after perturbation with anticancer drugs and matched clinical response of corresponding colorectal cancer patients. Our work opens new avenues for image-based profiling for accelerated drug discovery and clinical decision-making.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-07-31T15:54:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003141","title":"Whole transcriptome RNAseq of Ewing Sarcoma Cell Lines and blood plasma specimens, exosomal and cellular fractions","description":"This study aims to establish novel biomarkers suitable for non-invasive blood-based EwS detection, which could be beneficial for evaluating treatment efficacy and predicting relapse. As a potential source of such biomarkers, we considered exosomes, nanosized micro vesicles secreted by tumor cells. Exosomes were purified from the cultured A4573, TC32 and TC71 EwS cell lines and from blood plasma of EwS patients. Our study shows that global de-repression of constitutive heterochromatin observed at different stages of development, aging and cancer may have more far-reaching implications than previously anticipated. We demonstrate that multiple retroelement and pericentromeric transcripts with no apparent coding and replicative potential are transmitted in EwS exosomes into various immune cells and fibroblasts, where they exploit cellular machinery of the recipient cells for their amplification, packaging and further dissemination in the recipient cell exosomes.","abstract":"This study aims to establish novel biomarkers suitable for non-invasive blood-based EwS detection, which could be beneficial for evaluating treatment efficacy and predicting relapse. As a potential source of such biomarkers, we considered exosomes, nanosized micro vesicles secreted by tumor cells. Exosomes were purified from the cultured A4573, TC32 and TC71 EwS cell lines and from blood plasma of EwS patients. Our study shows that global de-repression of constitutive heterochromatin observed at different stages of development, aging and cancer may have more far-reaching implications than previously anticipated. We demonstrate that multiple retroelement and pericentromeric transcripts with no apparent coding and replicative potential are transmitted in EwS exosomes into various immune cells and fibroblasts, where they exploit cellular machinery of the recipient cells for their amplification, packaging and further dissemination in the recipient cell exosomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003142","title":"Whole exome sequencing of small cell neuroendocrine cancer of the cervix","description":"In order to improve treatment selection for high grade neuroendocrine carcinomas of the cervix (NECC), we performed a comparative genomic analysis between this rare tumor type and other cervical cancer types, as well as extra-cervical neuroendocrine small cell carcinomas of the lung and bladder. We performed whole exome sequencing on fresh-frozen tissue from 15 NECCs and matched normal tissue. We then identified mutations and copy number variants using standard analysis pipelines. Published mutation tables from cervical cancers and extra-cervical small cell carcinomas were used for comparative analysis. Descriptive statistical methods were used and a two-sided threshold of P &lt; .05 was used for significance. In the NECC cohort, we detected a median of 1.7 somatic mutations per megabase (range 1.0-20.9). PIK3CA p.E545K mutations were the most frequency observed oncogenic mutation (4/15 tumors, 27%). Activating MAPK pathway mutations in KRAS (p.G12D) and GNAS (p.R201C) co-occurred in two tumors (13%). In total we identified PI3-kinase or MAPK pathway activating mutations in 67% of NECC. When compared to NECC, lung and bladder small cell carcinomas exhibited a statistically significant higher rate of coding mutations (P &lt; .001 for lung; P = .001 for bladder). Mutation of TP53 was uncommon in NECC (13%) and was more frequent in both lung (103 of 110 tumors [94%], P &lt; .001) and bladder (18 of 19 tumors [95%], P &lt; .001) small cell carcinoma. These comparative genomics data suggest that NECC may be genetically more similar to common cervical cancer subtypes than to extra-cervical small cell neuroendocrine carcinomas of the lung and bladder. These results may have implications for the selection of cytotoxic and targeted therapy regimens for this rare disease.","abstract":"In order to improve treatment selection for high grade neuroendocrine carcinomas of the cervix (NECC), we performed a comparative genomic analysis between this rare tumor type and other cervical cancer types, as well as extra-cervical neuroendocrine small cell carcinomas of the lung and bladder. We performed whole exome sequencing on fresh-frozen tissue from 15 NECCs and matched normal tissue. We then identified mutations and copy number variants using standard analysis pipelines. Published mutation tables from cervical cancers and extra-cervical small cell carcinomas were used for comparative analysis. Descriptive statistical methods were used and a two-sided threshold of P &lt; .05 was used for significance. In the NECC cohort, we detected a median of 1.7 somatic mutations per megabase (range 1.0-20.9). PIK3CA p.E545K mutations were the most frequency observed oncogenic mutation (4/15 tumors, 27%). Activating MAPK pathway mutations in KRAS (p.G12D) and GNAS (p.R201C) co-occurred in two tumors (13%). In total we identified PI3-kinase or MAPK pathway activating mutations in 67% of NECC. When compared to NECC, lung and bladder small cell carcinomas exhibited a statistically significant higher rate of coding mutations (P &lt; .001 for lung; P = .001 for bladder). Mutation of TP53 was uncommon in NECC (13%) and was more frequent in both lung (103 of 110 tumors [94%], P &lt; .001) and bladder (18 of 19 tumors [95%], P &lt; .001) small cell carcinoma. These comparative genomics data suggest that NECC may be genetically more similar to common cervical cancer subtypes than to extra-cervical small cell neuroendocrine carcinomas of the lung and bladder. These results may have implications for the selection of cytotoxic and targeted therapy regimens for this rare disease.","study_type":"Other","pubmed_ids":[32544169],"external_links":null,"is_released":true,"released_date":"2018-07-31T22:40:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003143","title":"OICR_TEST","description":"OICR_TEST","abstract":"OICR_TEST","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003144","title":"Single cell sequencing of endoscopic biopsies from Barrett's oesophagus and proximal tissue from the normal GI tract","description":"Barrett’s oesophagus is a precursor of oesophageal adenocarcinoma. In this common condition, squamous epithelium in the oesophagus is replaced by columnar epithelium in response to acid reflux. Barrett’s oesophagus is highly heterogeneous and its relationships to normal tissues are unclear. We investigated the cellular complexity of Barrett’s oesophagus and the upper gastrointestinal tract using RNA-sequencing of single cells from multiple biopsies from six patients with Barrett’s oesophagus and two patients without oesophageal pathology.","abstract":"Barrett’s oesophagus is a precursor of oesophageal adenocarcinoma. In this common condition, squamous epithelium in the oesophagus is replaced by columnar epithelium in response to acid reflux. Barrett’s oesophagus is highly heterogeneous and its relationships to normal tissues are unclear. We investigated the cellular complexity of Barrett’s oesophagus and the upper gastrointestinal tract using RNA-sequencing of single cells from multiple biopsies from six patients with Barrett’s oesophagus and two patients without oesophageal pathology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-01T22:45:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003145","title":"A comprehensive human gastric cancer organoid biobank captures tumor subtype heterogeneity and enables therapeutic screening​","description":"Gastric cancer displays marked molecular heterogeneity with aggressive behavior and treatment resistance. Therefore, good in vitro models that encompass unique subtypes are urgently needed for precision medicine development. Here, we have established a primary gastric cancer organoid (GCO) biobank that comprises normal, dysplastic, cancer and lymph node metastases (n=63) from 34 patients, including detailed whole-exome and transcriptome analysis. The cohort encompasses most known molecular subtypes (including EBV, MSI, intestinal/CIN, and diffuse/GS, with CLDN18-ARHGAP6 or CTNND1-ARHGAP26 fusions or RHOA mutations), capturing regional heterogeneity and subclonal architecture, while their morphology, transcriptome, and genomic profiles remain closely similar to in vivo tumors, even after long-term culture. Large-scale drug screening revealed sensitivity to unexpected drugs that were recently approved or in clinical trials, including Napabucasin, Abemaciclib,  and the ATR inhibitor VE-822. Overall, this new GCO biobank, with linked genomic data, provides a useful resource for studying both cancer cell biology and precision cancer therapy.","abstract":"Gastric cancer displays marked molecular heterogeneity with aggressive behavior and treatment resistance. Therefore, good in vitro models that encompass unique subtypes are urgently needed for precision medicine development. Here, we have established a primary gastric cancer organoid (GCO) biobank that comprises normal, dysplastic, cancer and lymph node metastases (n=63) from 34 patients, including detailed whole-exome and transcriptome analysis. The cohort encompasses most known molecular subtypes (including EBV, MSI, intestinal/CIN, and diffuse/GS, with CLDN18-ARHGAP6 or CTNND1-ARHGAP26 fusions or RHOA mutations), capturing regional heterogeneity and subclonal architecture, while their morphology, transcriptome, and genomic profiles remain closely similar to in vivo tumors, even after long-term culture. Large-scale drug screening revealed sensitivity to unexpected drugs that were recently approved or in clinical trials, including Napabucasin, Abemaciclib,  and the ATR inhibitor VE-822. Overall, this new GCO biobank, with linked genomic data, provides a useful resource for studying both cancer cell biology and precision cancer therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-02T04:46:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003146","title":"RNA sequencing analysis of lymphoblastoid cell lines with wildtype or defective Epstein-Barr virus","description":"Lymphoblastoid cell lines established using either wildtype or BALF5-deficient Epstein-Barr virus were analyzed by RNA sequencing.","abstract":"Lymphoblastoid cell lines established using either wildtype or BALF5-deficient Epstein-Barr virus were analyzed by RNA sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003147","title":"DNA methylomes of monozygotic twins clinically discordant for multiple sclerosis","description":"Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Although genetic susceptibility is important, a modest concordance rate for MS in monozygotic (MZ) twins suggests that interaction with other risk factors is required to develop clinical symptoms. In this study, we examined whether DNA methylation differences contribute to the discordant clinical manifestation of MS in MZ twins, and studied the impact of MS treatments on the DNA methylome. Genome-wide DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) of 45 MZ twins clinically discordant for MS were generated using the Illumina HumanMethylationEPIC array. Repetitive element methylation and selected differentially methylated positions (DMPs) were validated using targeted deep bisulfite sequencing (TDBS). In addition, we performed whole genome bisulfite sequencing (WGBS) to profile CD4+ memory T-cells of a subset of four MS discordant MZ twins. Our results show that interferon treatment causes robust DNA methylation changes and several epigenetic biomarkers for interferon treatment response were identified. However, overall the PBMC-based methylomes of the MS discordant MZ twins were highly similar, since large systematic methylation differences (&gt;5%) were absent in the data. This suggests that previously reported large methylation changes are probably caused by genetic rather than epigenetic differences. In addition, our data does not support the hypothesis that the observed maternal parent-of-origin effect in MS is due to genomic imprinting errors, and no evidence was found that copy number variations explain the discordant phenotype in these MZ twins. Although not genome-wide significant, a couple of DMPs associated with the MS phenotype were identified and successfully technically replicated using TDBS, including a differentially methylated region (DMR) in the promoter of the transmembrane protein encoding gene TMEM232. Another MS-associated DMP, located in an enhancer in the gene body of the transcription factor ZBTB16, was also associated with medium-term glucocorticoid treatment history. WGBS analysis confirmed this DMP as a promising epigenetic biomarker for glucocorticoid treatment. In conclusion, this epigenome-wide association study (EWAS) in genetically identical twins identified a DMR in the TMEM232 promoter as a candidate loci associated with the clinical manifestation of MS. In addition, epigenetic biomarkers for MS treatments were identified, revealing that not only short-term, but also medium-term treatment effects are detectable in immune cells, which should be taken into account in future EWAS designs.","abstract":"Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Although genetic susceptibility is important, a modest concordance rate for MS in monozygotic (MZ) twins suggests that interaction with other risk factors is required to develop clinical symptoms. In this study, we examined whether DNA methylation differences contribute to the discordant clinical manifestation of MS in MZ twins, and studied the impact of MS treatments on the DNA methylome. Genome-wide DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) of 45 MZ twins clinically discordant for MS were generated using the Illumina HumanMethylationEPIC array. Repetitive element methylation and selected differentially methylated positions (DMPs) were validated using targeted deep bisulfite sequencing (TDBS). In addition, we performed whole genome bisulfite sequencing (WGBS) to profile CD4+ memory T-cells of a subset of four MS discordant MZ twins. Our results show that interferon treatment causes robust DNA methylation changes and several epigenetic biomarkers for interferon treatment response were identified. However, overall the PBMC-based methylomes of the MS discordant MZ twins were highly similar, since large systematic methylation differences (&gt;5%) were absent in the data. This suggests that previously reported large methylation changes are probably caused by genetic rather than epigenetic differences. In addition, our data does not support the hypothesis that the observed maternal parent-of-origin effect in MS is due to genomic imprinting errors, and no evidence was found that copy number variations explain the discordant phenotype in these MZ twins. Although not genome-wide significant, a couple of DMPs associated with the MS phenotype were identified and successfully technically replicated using TDBS, including a differentially methylated region (DMR) in the promoter of the transmembrane protein encoding gene TMEM232. Another MS-associated DMP, located in an enhancer in the gene body of the transcription factor ZBTB16, was also associated with medium-term glucocorticoid treatment history. WGBS analysis confirmed this DMP as a promising epigenetic biomarker for glucocorticoid treatment. In conclusion, this epigenome-wide association study (EWAS) in genetically identical twins identified a DMR in the TMEM232 promoter as a candidate loci associated with the clinical manifestation of MS. In addition, epigenetic biomarkers for MS treatments were identified, revealing that not only short-term, but also medium-term treatment effects are detectable in immune cells, which should be taken into account in future EWAS designs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-02T23:11:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003148","title":"Copy-choice recombination during mitochondrial L-strand synthesis causes DNA deletions","description":"Mitochondrial DNA (mtDNA) deletions are associated with mitochondrial disease, and also accumulate during normal human ageing. The mechanisms underlying mtDNA deletions remain unknown although several models have been proposed. Here we use deep sequencing to characterize abundant mtDNA deletions in patients with mutations in POLG, the gene encoding mitochondrial DNA polymerase, and show that these have distinct directionality and repeat characteristics. Furthermore, we recreate the deletion formation process in vitro using only purified mitochondrial proteins and defined DNA templates. Based on our in vivo and in vitro findings, we conclude that mtDNA deletion formation involves copy-choice recombination during replication of the mtDNA light strand.","abstract":"Mitochondrial DNA (mtDNA) deletions are associated with mitochondrial disease, and also accumulate during normal human ageing. The mechanisms underlying mtDNA deletions remain unknown although several models have been proposed. Here we use deep sequencing to characterize abundant mtDNA deletions in patients with mutations in POLG, the gene encoding mitochondrial DNA polymerase, and show that these have distinct directionality and repeat characteristics. Furthermore, we recreate the deletion formation process in vitro using only purified mitochondrial proteins and defined DNA templates. Based on our in vivo and in vitro findings, we conclude that mtDNA deletion formation involves copy-choice recombination during replication of the mtDNA light strand.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-03T13:50:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003149","title":"Single_cell_analysis_of_Neutrophils","description":"Neutrophils are the most abundant white blood cells and fulfil a critical function in the human immune system.  Their effector functions comprise the phagocytosis of bacteria, the release of antimicrobial agents by degranulation, the production of reactive oxygen species (ROS) and the formation of neutrophil extracellular traps (NETs). Despite of their function of trapping and killing bacteria, NETs seem to play a role in the development of autoimmune diseases. The insufficient clearance of NETs as it occurs for example in patients with systemic lupus erythematosus (SLE) could contribute the hallmarks of this disease: the production auf autoantibodies and a type I interferon signature. \nAlthough neutrophils are produced with a high rate of 5x1010 cells/ day and play an important role in the immune defense, they are poorly studied. Their terminal differentiation status and their short life span (6-8h in circulation) make genetic manipulation very difficult. Despite experimental evidence showing that not all neutrophils react to stimulations the same way, no neutrophil subpopulations are described yet. In order to address this important question we will perform single cell RNA sequencing (scRNAseq) of Neutrophils at the Sanger Institute.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Neutrophils are the most abundant white blood cells and fulfil a critical function in the human immune system.  Their effector functions comprise the phagocytosis of bacteria, the release of antimicrobial agents by degranulation, the production of reactive oxygen species (ROS) and the formation of neutrophil extracellular traps (NETs). Despite of their function of trapping and killing bacteria, NETs seem to play a role in the development of autoimmune diseases. The insufficient clearance of NETs as it occurs for example in patients with systemic lupus erythematosus (SLE) could contribute the hallmarks of this disease: the production auf autoantibodies and a type I interferon signature. \nAlthough neutrophils are produced with a high rate of 5x1010 cells/ day and play an important role in the immune defense, they are poorly studied. Their terminal differentiation status and their short life span (6-8h in circulation) make genetic manipulation very difficult. Despite experimental evidence showing that not all neutrophils react to stimulations the same way, no neutrophil subpopulations are described yet. In order to address this important question we will perform single cell RNA sequencing (scRNAseq) of Neutrophils at the Sanger Institute.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003150","title":"ImmunoAgeing_Longitudinal_TGS_Controls","description":"An investigation of the role of immunosenescence in the development of clonal haematopoiesis.","abstract":"The objective is to establish whether immunosenescence is associated with the development of clonal haematopoiesis in a healthy ageing population. This will be addressed in collaboration with the European consortium running the ImmunoAgeing project (www.immunoageing.eu).   \nGenomic DNA derived from the peripheral blood of 394 individuals at 3-5 time-points over a 20-year period will be analysed. RNA bait pulldown (Agilent) will be used to perform targeted sequencing of genes known to be recurrently mutated in myeloid malignancies\nThe presence, size and nature of clonal haematopoiesis will be correlated with quantitative measures of immunosenescence.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003151","title":"MutWP4__CRUK_Grand_Challenge_Mutographs_of_Cancer__Gastric_Organoids","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, Kings College London will characterise the mutational signatures induced by putative human carcinogens in order to identify the origins of mutational signatures found in human cancers. To achieve this human organoid cell cultures will be exposed to a representative catalogue of known or suspected human carcinogens and mutagens and, using whole genome sequencing, the patterns of mutations induced by them will be determined. Somatic mutational signatures will be subsequently extracted by non-negative matrix factorisation methods and correlated with exposure data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, Kings College London will characterise the mutational signatures induced by putative human carcinogens in order to identify the origins of mutational signatures found in human cancers. To achieve this human organoid cell cultures will be exposed to a representative catalogue of known or suspected human carcinogens and mutagens and, using whole genome sequencing, the patterns of mutations induced by them will be determined. Somatic mutational signatures will be subsequently extracted by non-negative matrix factorisation methods and correlated with exposure data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-08T14:44:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003152","title":"A machine learning approach for somatic mutation discovery","description":"Variability in the accuracy for somatic mutation detection may affect discovery of alterations and therapeutic management of cancer patients.  To address this issue, we developed a somatic mutation discovery approach based on machine learning that outperformed other methods in identifying tumor alterations that were experimentally validated","abstract":"Variability in the accuracy for somatic mutation detection may affect discovery of alterations and therapeutic management of cancer patients.  To address this issue, we developed a somatic mutation discovery approach based on machine learning that outperformed other methods in identifying tumor alterations that were experimentally validated","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003153","title":"Comprehensive genetic analysis of chronic active Epstein-Barr virus infection","description":"Comprehensive genetic analyses including whole-exome sequencing, targeted sequencing, and whole-genome sequencing were performed to reveal the molecular pathogenesis of chronic active Epstein-Barr virus infection.","abstract":"Comprehensive genetic analyses including whole-exome sequencing, targeted sequencing, and whole-genome sequencing were performed to reveal the molecular pathogenesis of chronic active Epstein-Barr virus infection.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003154","title":"Sequencing_of_patient_samples_who_received_immune_checkpoint_inhibition___WES___NKI","description":"DNA and RNA isolated from FFPE blocks of patients who received immune checkpoint inhibition (ICI) are sequenced with the aim to identify therapeutically tractable vulnerabilities in tumors to prevent ICI resistance.","abstract":"The clinical outcome of late-stage melanoma patients has greatly improved thanks to the recent availability of targeted therapy and T cell checkpoint modulation, primarily CTLA-4 and PD-1/PD-L1 blockade. Also, for advanced non-small cell lung cancer, anti-PD-(L)1 antibody prolongs patient survival and has therefore been approved as first- and second-line treatments. Despite these advances, however, for immune checkpoint inhibition (ICI) of both these cancer types, most patients fail to (durably) benefit mainly because of primary, adaptive, and acquired therapy resistance. Crucially, our understanding of the underlying mechanisms of ICI resistance is only fragmentary, as is our ability to predict which patients are likely to fail on to therapy. We will analyse the RNA/DNA sequence data to increase our understanding of (acquired-) resistance and with the aim to identify therapeutically tractable vulnerabilities in tumors to prevent ICI resistance.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-09T15:34:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003155","title":"High Altitude Pulmonary Hypertension","description":"The Central Asian Kyrgyz highland population provides a unique opportunity to address genetic diversity and understand the genetic mechanisms underlying hypoxia-induced high altitude pulmonary hypertension (HAPH). While a significant fraction of the population is unaffected, there are susceptible individuals who display HAPH in the absence of any lung, cardiac or hematologic disease. We report herein the analysis of the whole genome sequencing of healthy individuals compared with HAPH patients and other controls.","abstract":"The Central Asian Kyrgyz highland population provides a unique opportunity to address genetic diversity and understand the genetic mechanisms underlying hypoxia-induced high altitude pulmonary hypertension (HAPH). While a significant fraction of the population is unaffected, there are susceptible individuals who display HAPH in the absence of any lung, cardiac or hematologic disease. We report herein the analysis of the whole genome sequencing of healthy individuals compared with HAPH patients and other controls.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003156","title":"Whole-genome sequencing of Epstein-Barr virus in hematological malignancy","description":"Capture-based whole-genome sequencing of Epstein-Barr virus (EBV) was performed in hematological malignancies such as EBV-positive diffuse large B-cell lymphoma, extranodal NK/T-cell lymphoma, and chronic active EBV infection.","abstract":"Capture-based whole-genome sequencing of Epstein-Barr virus (EBV) was performed in hematological malignancies such as EBV-positive diffuse large B-cell lymphoma, extranodal NK/T-cell lymphoma, and chronic active EBV infection.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003157","title":"Partially methylated domains across multiple cell types","description":"Partially methylated domains are extended regions in the genome exhibiting a reduced average DNA methylation level. They cover gene poor and transcriptionally inactive regions and tend to be heterochromatic. We present a comprehensive comparative analysis of partially methylated domains in human and mouse cells, to identify structural and functional features associated with them.","abstract":"Partially methylated domains are extended regions in the genome exhibiting a reduced average DNA methylation level. They cover gene poor and transcriptionally inactive regions and tend to be heterochromatic. We present a comprehensive comparative analysis of partially methylated domains in human and mouse cells, to identify structural and functional features associated with them.","study_type":"Other","pubmed_ids":[30266094],"external_links":null,"is_released":true,"released_date":"2018-08-10T10:04:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003158","title":"DNA Methylation-based diagnostic biomarkers for ESCC in Han Chinese population","description":"DNA methylation-based biomarkers were suggested to be promising for early cancer diagnosis. However, DNA methylation-based biomarkers for esophageal squamous cell carcinoma (ESCC), especially in Chinese Han populations have not been identified and evaluated quantitatively. To identify the candidate DNA-methylation based biomarkers for ESCC diagnosis, we performed the targeted bisulfite sequencing analysis in this study.  Based on these 94 pairs of ESCC tumors and adjacent normal tissues, we found out that ADHFE1, EOMES, SALL1 and TFPI2 could be an effective methylation-based assay for ESCC diagnosis.","abstract":"DNA methylation-based biomarkers were suggested to be promising for early cancer diagnosis. However, DNA methylation-based biomarkers for esophageal squamous cell carcinoma (ESCC), especially in Chinese Han populations have not been identified and evaluated quantitatively. To identify the candidate DNA-methylation based biomarkers for ESCC diagnosis, we performed the targeted bisulfite sequencing analysis in this study.  Based on these 94 pairs of ESCC tumors and adjacent normal tissues, we found out that ADHFE1, EOMES, SALL1 and TFPI2 could be an effective methylation-based assay for ESCC diagnosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-10T15:47:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003159","title":"Comprehensive genetic analysis of Epstein-Barr virus-associated hematological malignancy","description":"Comprehensive genetic analyses including whole-exome sequencing, targeted sequencing, and whole-genome sequencing of the human genome and the Epstein-Barr virus (EBV) genome were performed to reveal the molecular pathogenesis of EBV-associated hematological malignancy.","abstract":"Comprehensive genetic analyses including whole-exome sequencing, targeted sequencing, and whole-genome sequencing of the human genome and the Epstein-Barr virus (EBV) genome were performed to reveal the molecular pathogenesis of EBV-associated hematological malignancy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-14T09:47:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003160","title":"Tumor-associated preferred end coordinates and somatic variants as signatures of circulating tumor DNA","description":"Cell-free DNA fragmentation is a nonrandom process. We showed that cell-free DNA fragments with ends at certain genomic coordinates had higher likelihoods of being derived from hepatocellular carcinoma. Other coordinates were associated with cell-free DNA molecules originating from the liver. Quantitative assessment of cell-free DNA molecules bearing these respective groups of end signatures correlated with the amounts of tumor-derived or liver-derived DNA in plasma. There were millions of tumor-associated plasma DNA end coordinates across the genome. Due to their high prevalence, they were more readily detectable than somatic mutations as a cancer signature in plasma. Hence, detection of tumor-associated plasma DNA ends may offer a cost-effective means of capturing evidence for the presence of cancer through liquid biopsy assessment.","abstract":"Cell-free DNA fragmentation is a nonrandom process. We showed that cell-free DNA fragments with ends at certain genomic coordinates had higher likelihoods of being derived from hepatocellular carcinoma. Other coordinates were associated with cell-free DNA molecules originating from the liver. Quantitative assessment of cell-free DNA molecules bearing these respective groups of end signatures correlated with the amounts of tumor-derived or liver-derived DNA in plasma. There were millions of tumor-associated plasma DNA end coordinates across the genome. Due to their high prevalence, they were more readily detectable than somatic mutations as a cancer signature in plasma. Hence, detection of tumor-associated plasma DNA ends may offer a cost-effective means of capturing evidence for the presence of cancer through liquid biopsy assessment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-15T05:12:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003161","title":"DNAseq_human_cultures_OE_Albert","description":"Analysis of clonal expansion by sequencing in human primary cultures.","abstract":"Grid sequencing of primary human cultures for analysing clonal expansion in OE keratinocytes in culture.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003162","title":"Single_cell_resolution_of_human_CNV_body_map","description":"12 tissues from the warm autopsy are selected for this project. Using 10X Chromium technology we will generate ~1000 single cell/nulei genomic libraries per tissue.  Each tissue will be whole genome sequenced (~2 lanes per 1000 cells) on hiseq X10. per single cell we will generate CNV profile and we investigate the level of genomic heterogenity with in tissue and across different tissues.","abstract":"This project aims to produce a high resolution of human CNV body map using 10X Chromium on frozen blocks of ~12 different tissues from the warm autopsy.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-15T10:45:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003163","title":"ChIP-seq data of H3K4me3, H3K27ac and H3K27me3 on multiple human embryonic tissues.","description":"The regulatory landscape of the human genome during organogenesis is undescribed for most tissues. We used ChIP-seq to survey histone modifications in 13 human embryonic tissues.  We describe patterns of both common and tissue-specific marking of promoter activation and repression and use enhancer usage to infer regulatory pathways.","abstract":"The regulatory landscape of the human genome during organogenesis is undescribed for most tissues. We used ChIP-seq to survey histone modifications in 13 human embryonic tissues.  We describe patterns of both common and tissue-specific marking of promoter activation and repression and use enhancer usage to infer regulatory pathways.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-16T12:32:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003164","title":"Whole genome sequencing of multiple myeloma identifies novel structural and non-coding mutations.","description":"The coding region of the myeloma genome is well understood with key mutations having been identified.  However, the non-coding regions of the myeloma genome are yet to be analyzed. Here we have performed whole genome sequencing  of myeloma patient samples to identify structural abnormalities including chromothripsis and chromoplexy, as well as gene dysregulation through super-enhancer juxtaposition with key oncogenes.  We have also identified non-coding region hotspots of mutation, especially in promoter regions, that affect gene expression.","abstract":"The coding region of the myeloma genome is well understood with key mutations having been identified.  However, the non-coding regions of the myeloma genome are yet to be analyzed. Here we have performed whole genome sequencing  of myeloma patient samples to identify structural abnormalities including chromothripsis and chromoplexy, as well as gene dysregulation through super-enhancer juxtaposition with key oncogenes.  We have also identified non-coding region hotspots of mutation, especially in promoter regions, that affect gene expression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-16T16:08:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003165","title":"iNeuron_ChIPseq","description":"Characterisation of the chromatin status of induced neurons (iNeurons) generated by overexpression of the Ngn2 transcription factor transgenically in BOB iPS cells at the excitatory cortical neuron and iPSC stages. The aim is to understand the differentiation trajectory and characterise the chromatin status so that we can understand the impact of chromatin on gene expression during this transition.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Characterisation of the chromatin status of induced neurons (iNeurons) generated by overexpression of the Ngn2 transcription factor transgenically in BOB iPS cells at the excitatory cortical neuron and iPSC stages. The aim is to understand the differentiation trajectory and characterise the chromatin status so that we can understand the impact of chromatin on gene expression during this transition.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-16T17:00:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003166","title":"Cancer_class_switch___scNMT_seq","description":"Single cell chromatin accessibility and methylation sequencing of two distinct leukemias in a case of cancer class switch","abstract":"We study the unique case of a cancer class switch in a child presenting with two subsequent cases of leukemias of a presumed shared lineage. We collect a combination of whole genome, single-cell RNA-seq and scNMT-seq data to identify the common ancestor and analyse underlying mechanisms of oncogenesis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003167","title":"Repeated_clinical_malaria_episodes_are_associated_with_modification_of_the_immune_system_in_children_","description":"Repeated clinical malaria episodes are associated with modification of the immune system in children.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/.","abstract":"Background: There are over 200 million reported cases of malaria each year, and most children living in endemic areas will experience multiple episodes of clinical disease before puberty. We set out to understand how frequent clinical malaria, which elicits a strong inflammatory response, affects the immune system and whether these modifications are observable in the absence of detectable parasitemia. \nMethods: We used a multi-dimensional approach comprising whole blood transcriptomic, cellular and plasma cytokine analyses on a cohort of children living with endemic malaria, but uninfected at sampling, who had been under active surveillance for malaria for eight years. Children were categorised into two groups depending on the cumulative number of episodes experienced: high (&gt;=8) or low (&lt;5). \nResults: We observe that multiple episodes of malaria are associated with modification of the immune system. Children who had experienced a large number of episodes demonstrated upregulation of interferon-inducible genes, a clear increase in circulating levels of the immunoregulatory cytokine IL-10 and enhanced activation of neutrophils, B cells and CD8+ T cells. \nConclusion: Transcriptomic analysis together with cytokine and immune cell profiling of peripheral blood can robustly detect immune differences between children with different numbers of prior malaria episodes. Multiple episodes of malaria are associated with modification of the immune system in children. Such immune modifications may have implications for the initiation of subsequent immune responses and the induction of vaccine-mediated protection.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-20T16:03:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003168","title":"Primary breast tumor heterogeneity through therapy","description":"We performed whole-exome sequencing on multiple regions (n=2-3) from four primary untreated breast tumors (n=1 HER2+, n=2 ER+/HER2-, n=1 triple-negative), as well as matched normal. We also performed whole-exome sequencing on one region from the pre-treatment diagnostic core biopsy and multiple regions (n=2-6) from the post-treatment surgical specimen for five HER2+ primary breast tumors, as well as matched normal; all were treated with combination chemotherapy and trastuzumab. Analysis of these specimens allows characterization of breast tumor heterogeneity and clonal evolution.","abstract":"We performed whole-exome sequencing on multiple regions (n=2-3) from four primary untreated breast tumors (n=1 HER2+, n=2 ER+/HER2-, n=1 triple-negative), as well as matched normal. We also performed whole-exome sequencing on one region from the pre-treatment diagnostic core biopsy and multiple regions (n=2-6) from the post-treatment surgical specimen for five HER2+ primary breast tumors, as well as matched normal; all were treated with combination chemotherapy and trastuzumab. Analysis of these specimens allows characterization of breast tumor heterogeneity and clonal evolution.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-20T18:34:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003169","title":"DDD_Main","description":"These samples are part of the DDD Main dataset\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"These samples are part of the DDD Main dataset","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003170","title":"Childhood cerebellar tumors mirror conserved fetal transcriptional programs","description":"We used single-cell transcriptomics to study &gt;60,000 cells from the developing murine cerebellum, and show that different molecular subgroups of childhood cerebellar tumors mirror the transcription of cells from distinct, temporally restricted cerebellar lineages.","abstract":"We used single-cell transcriptomics to study &gt;60,000 cells from the developing murine cerebellum, and show that different molecular subgroups of childhood cerebellar tumors mirror the transcription of cells from distinct, temporally restricted cerebellar lineages.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-21T20:09:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003171","title":"High Altitude Pulmonary Hypertension","description":"The Central Asian Kyrgyz highland population provides a unique opportunity to address genetic diversity and understand the genetic mechanisms underlying hypoxia-induced high altitude pulmonary hypertension (HAPH). While a significant fraction of the population is unaffected, there are susceptible individuals who display HAPH in the absence of any lung, cardiac or hematologic disease. We report herein the analysis of the whole genome sequencing of healthy individuals compared with HAPH patients and other controls.","abstract":"The Central Asian Kyrgyz highland population provides a unique opportunity to address genetic diversity and understand the genetic mechanisms underlying hypoxia-induced high altitude pulmonary hypertension (HAPH). While a significant fraction of the population is unaffected, there are susceptible individuals who display HAPH in the absence of any lung, cardiac or hematologic disease. We report herein the analysis of the whole genome sequencing of healthy individuals compared with HAPH patients and other controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-22T06:14:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003172","title":"“Castration-persistence” is a distinct state of tolerance to androgen receptor targeting therapies in prostate cancer","description":"Androgen receptor (AR) signalling is important in prostate cancer progression, and therapies that specifically target this pathway are the mainstay of treatment for advanced disease. Treatment however is non-curative, and resistance develops inevitably with time. Although the mechanisms that drive progressive ‘castration resistant’ disease are reasonably well characterized, how tumours survive acute pathway inhibition is unclear. We performed a neo-adjuvant study of a novel combination of AR targeting therapies, and noted that the objective response to treatment was highly variable. To determine what was driving tumour persistence in poorly responding patients, we comprehensively characterised pre- and post-treatment samples were using both whole genome and RNA-sequencing. We find that ‘castration-persistence’ is a distinct state from ‘castration-resistance’, and is mediated by global transcriptional reprogramming leading to transitional EMT state, which is shared with benign luminal epithelial cells. This appears to be AP-1 and KLF driven, and represents and integration of multiple signalling pathways, particularly IGF2, offering a number of tractable strategies to improve clinical response to AR targeting therapies.","abstract":"Androgen receptor (AR) signalling is important in prostate cancer progression, and therapies that specifically target this pathway are the mainstay of treatment for advanced disease. Treatment however is non-curative, and resistance develops inevitably with time. Although the mechanisms that drive progressive ‘castration resistant’ disease are reasonably well characterized, how tumours survive acute pathway inhibition is unclear. We performed a neo-adjuvant study of a novel combination of AR targeting therapies, and noted that the objective response to treatment was highly variable. To determine what was driving tumour persistence in poorly responding patients, we comprehensively characterised pre- and post-treatment samples were using both whole genome and RNA-sequencing. We find that ‘castration-persistence’ is a distinct state from ‘castration-resistance’, and is mediated by global transcriptional reprogramming leading to transitional EMT state, which is shared with benign luminal epithelial cells. This appears to be AP-1 and KLF driven, and represents and integration of multiple signalling pathways, particularly IGF2, offering a number of tractable strategies to improve clinical response to AR targeting therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-22T08:51:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003173","title":"Primary breast cancers and paired brain metastases sequencing study","description":"Improving management of brain metastases (BM) from primary breast cancer (PBC) is a challenge in which targeted therapies play a promising role. However this approach is impaired by miss-knowledge of molecular patterns of the metastatic and drug-resistance processes.We performed a differential analysis of copy-number-alterations (CNAs) and mutations profiles by using pan-genomic array-CGH and targeted next-generation-sequencing of  494 cancer-associated genes, in a series of 14 pairs of matched PBC/BM and assessed if the observed genomic alterations may be used as a druggable agent in a clinical trial.","abstract":"Improving management of brain metastases (BM) from primary breast cancer (PBC) is a challenge in which targeted therapies play a promising role. However this approach is impaired by miss-knowledge of molecular patterns of the metastatic and drug-resistance processes.We performed a differential analysis of copy-number-alterations (CNAs) and mutations profiles by using pan-genomic array-CGH and targeted next-generation-sequencing of  494 cancer-associated genes, in a series of 14 pairs of matched PBC/BM and assessed if the observed genomic alterations may be used as a druggable agent in a clinical trial.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-22T10:07:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003174","title":"Dnase1l3 knockout causes aberrations in plasma DNA fragmentation","description":"Dnase1l3 knockout causes aberrations in plasma DNA fragmentation","abstract":"Dnase1l3 knockout causes aberrations in plasma DNA fragmentation","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-22T16:12:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003175","title":"Targeted_sequencing_of_in_vitro_colonies___bulks","description":"In this study we will perform targeted sequencing on the bulk samples of in vitro colonies","abstract":"In this study we will perform targeted sequencing on the bulk samples of in vitro colonies","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-23T11:10:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003176","title":"Study the differences at the trascriptome level between iNKT and T cells","description":"Chimeric antigen receptor anti-CD19 (CAR19)-T cell immunotherapy-induced clinical remissions in CD19+ B cell lymphomas are often short-lived. We tested whether CAR19-engineering of the CD1d-restricted invariant NKT (iNKT) cells would result in enhanced anti-lymphoma activity. CAR19-iNKT cells co-operatively activated by CD1d- and CAR19-CD19-dependent interactions are more effective than CAR19-T cells against CD1d-expressing lymphomas in vitro and in vivo. The swifter in vivo anti-lymphoma activity of CAR19-iNKT cells and their enhanced ability to eradicate brain lymphomas underpinned an improved tumor-free and overall survival. CD1d transcriptional de-repression by all-trans retinoic acid results in further enhanced cytotoxicity of CAR19-iNKT cells against CD19+ chronic lymphocytic leukemia cells. Thus, iNKT cells are a highly efficient platform for CAR-based immunotherapy of lymphomas and possibly other CD1d-expressing cancers.","abstract":"Chimeric antigen receptor anti-CD19 (CAR19)-T cell immunotherapy-induced clinical remissions in CD19+ B cell lymphomas are often short-lived. We tested whether CAR19-engineering of the CD1d-restricted invariant NKT (iNKT) cells would result in enhanced anti-lymphoma activity. CAR19-iNKT cells co-operatively activated by CD1d- and CAR19-CD19-dependent interactions are more effective than CAR19-T cells against CD1d-expressing lymphomas in vitro and in vivo. The swifter in vivo anti-lymphoma activity of CAR19-iNKT cells and their enhanced ability to eradicate brain lymphomas underpinned an improved tumor-free and overall survival. CD1d transcriptional de-repression by all-trans retinoic acid results in further enhanced cytotoxicity of CAR19-iNKT cells against CD19+ chronic lymphocytic leukemia cells. Thus, iNKT cells are a highly efficient platform for CAR-based immunotherapy of lymphomas and possibly other CD1d-expressing cancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-24T18:19:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003177","title":"A Single Complex Agpat2 Allele In A Patient With Partial  Lipodystrophy","description":"Genetic lipodystrophies are a group of rare syndromes associated with major metabolic complications - including severe insulin resistance, type 2 diabetes mellitus, and hypertriglyceridemia - which are classified according to the distribution of adipose tissue. Lipodystrophies can be present at birth or develop during life and can range from local to partial and general. With at least 18 different genes implicated so far, definite diagnosis can be challenging due to clinical and genetic heterogeneity. In an adult female patient with clinical and metabolic features of partial lipodystrophy we identified via whole genome sequencing a single complex AGPAT2 allele [V67M;V167A], functionally equivalent to heterozygosity. AGPAT2 encodes for an acyltransferase implicated in the biosynthesis of triacylglycerol and glycerophospholipids. So far homozygous and compound heterozygous mutations in AGPAT2 have only been associated with generalized lipodystrophy. A SNP risk score analysis indicated that the index patient is not predisposed to lipodystrophy based on her genetic background. The partial phenotype in our patient is therefore more likely associated to the genetic variants in AGPAT2. To test whether the resulting double-mutant AGPAT2 protein is functional we analysed its in vitro enzymatic activity via mass spectrometry.  The resulting AGPAT2 double mutant is enzymatically inactive. Our data support the view that the current classification of lipodystrophies as strictly local, partial or generalized may have to be re-evaluated and viewed more as a continuum, both in terms of clinical presentation and underlying genetic causes. Better molecular understanding of lipodystrophies may lead to new therapies to treat adipose tissue dysfunction in common and rare diseases.","abstract":"Genetic lipodystrophies are a group of rare syndromes associated with major metabolic complications - including severe insulin resistance, type 2 diabetes mellitus, and hypertriglyceridemia - which are classified according to the distribution of adipose tissue. Lipodystrophies can be present at birth or develop during life and can range from local to partial and general. With at least 18 different genes implicated so far, definite diagnosis can be challenging due to clinical and genetic heterogeneity. In an adult female patient with clinical and metabolic features of partial lipodystrophy we identified via whole genome sequencing a single complex AGPAT2 allele [V67M;V167A], functionally equivalent to heterozygosity. AGPAT2 encodes for an acyltransferase implicated in the biosynthesis of triacylglycerol and glycerophospholipids. So far homozygous and compound heterozygous mutations in AGPAT2 have only been associated with generalized lipodystrophy. A SNP risk score analysis indicated that the index patient is not predisposed to lipodystrophy based on her genetic background. The partial phenotype in our patient is therefore more likely associated to the genetic variants in AGPAT2. To test whether the resulting double-mutant AGPAT2 protein is functional we analysed its in vitro enzymatic activity via mass spectrometry.  The resulting AGPAT2 double mutant is enzymatically inactive. Our data support the view that the current classification of lipodystrophies as strictly local, partial or generalized may have to be re-evaluated and viewed more as a continuum, both in terms of clinical presentation and underlying genetic causes. Better molecular understanding of lipodystrophies may lead to new therapies to treat adipose tissue dysfunction in common and rare diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-27T12:24:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003178","title":"Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma","description":"We conducted a randomized phase II study of neoadjuvant nivolumab versus combined ipilimumab with nivolumab in 23 patients with high-risk resectable melanoma (NCT02519322) and assessed clinical responses and immune correlates. Treatment with combined ipilimumab and nivolumab yielded high response rates (RECIST overall response rate 73%, pathologic complete response rate 45%) but substantial toxicity (73% grade 3 treatment related adverse events), whereas treatment with nivolumab monotherapy yielded modest responses (RECIST overall response rate 25%, pathologic complete response rate 25%) and low toxicity (8% grade 3 treatment related adverse events). Immune correlates of response were identified, demonstrating higher lymphoid infiltrates in responders to both therapies and a more clonal and diverse T cell infiltrate in responders to nivolumab monotherapy. Mutational load was also higher in responders to therapy.","abstract":"We conducted a randomized phase II study of neoadjuvant nivolumab versus combined ipilimumab with nivolumab in 23 patients with high-risk resectable melanoma (NCT02519322) and assessed clinical responses and immune correlates. Treatment with combined ipilimumab and nivolumab yielded high response rates (RECIST overall response rate 73%, pathologic complete response rate 45%) but substantial toxicity (73% grade 3 treatment related adverse events), whereas treatment with nivolumab monotherapy yielded modest responses (RECIST overall response rate 25%, pathologic complete response rate 25%) and low toxicity (8% grade 3 treatment related adverse events). Immune correlates of response were identified, demonstrating higher lymphoid infiltrates in responders to both therapies and a more clonal and diverse T cell infiltrate in responders to nivolumab monotherapy. Mutational load was also higher in responders to therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-27T19:53:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003179","title":"Molecular origins of mpMRI visibility","description":"Multiparametric magnetic resonance imaging (mpMRI) has transformed the landscape of prostate cancer (PCa) management. Prostate Imaging Reporting and Data System (PI-RADSv2) scores reflect function and correlate phenotypic features with tumor aggressiveness, is an independent predictor of biochemical recurrence, and may distinguish low-risk tumors requiring no treatment from high-risk tumors requiring aggressive management. We hypothesize that differences in functional mpMRI of prostate tumors reflect the genetic and epigenetic heterogeneity of PCa. We profiled the genomes and transcriptomes of 40 Gleason score 3+4 tumors, of which 20 tumors were mpMRI invisible (not PI-RADSv2 3-5) and 20 tumors were visible (PI-RADSv2 5). Genomes of visible tumors were more unstable than those of invisible tumors. We identified 62 enriched transcripts, including numerous snoRNAs, Relaxin 1 and SCHLAP1, in visible tumors. These data suggest a confluence of aggressive pathological and microenvironmental phenomenon in PI-RADSv2 5 tumors reminiscent of nimbosus, while linking the molecular profiles of tumor aggressiveness with their functional features on mpMRI.","abstract":"Multiparametric magnetic resonance imaging (mpMRI) has transformed the landscape of prostate cancer (PCa) management. Prostate Imaging Reporting and Data System (PI-RADSv2) scores reflect function and correlate phenotypic features with tumor aggressiveness, is an independent predictor of biochemical recurrence, and may distinguish low-risk tumors requiring no treatment from high-risk tumors requiring aggressive management. We hypothesize that differences in functional mpMRI of prostate tumors reflect the genetic and epigenetic heterogeneity of PCa. We profiled the genomes and transcriptomes of 40 Gleason score 3+4 tumors, of which 20 tumors were mpMRI invisible (not PI-RADSv2 3-5) and 20 tumors were visible (PI-RADSv2 5). Genomes of visible tumors were more unstable than those of invisible tumors. We identified 62 enriched transcripts, including numerous snoRNAs, Relaxin 1 and SCHLAP1, in visible tumors. These data suggest a confluence of aggressive pathological and microenvironmental phenomenon in PI-RADSv2 5 tumors reminiscent of nimbosus, while linking the molecular profiles of tumor aggressiveness with their functional features on mpMRI.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-28T13:46:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003180","title":"Profiling of Peritoneal Metastases from Gastric Adenocarcinoma Identified Molecular Subtypes","description":"Peritoneal carcinomatosis (PC) occurs frequently in gastric adenocarcinoma (GAC) patients and confers poor prognosis. Multiplex profiling of primary GACs has been insightful but the underpinnings of PC’s development/progression remain largely unknown. Here we characterized exome/transcriptome/immune landscapes of PC cells from 43 patients.","abstract":"Peritoneal carcinomatosis (PC) occurs frequently in gastric adenocarcinoma (GAC) patients and confers poor prognosis. Multiplex profiling of primary GACs has been insightful but the underpinnings of PC’s development/progression remain largely unknown. Here we characterized exome/transcriptome/immune landscapes of PC cells from 43 patients.","study_type":"Other","pubmed_ids":[31171626],"external_links":null,"is_released":true,"released_date":"2018-08-29T07:28:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003181","title":"Population_dynamics_in_abnormal_haematopoiesis","description":"Background: Our recent study has made direct insight into the clonal dynamics of blood cell production in an unperturbed setting in a human. Using whole genome sequencing to track acquired somatic mutations, we were able to construct a phylogenetic tree of different stem and progenitor cells and used this tree to determine the dynamics of mature blood cell production in longitudinal samples. These data set the baseline for understanding population dynamics in abnormal haematopoiesis, and how malignant clones outcompete their normal counterparts to drive haematological malignancies.\nAim: This  study will measure population dynamics in abnormal human haematopoiesis in patients with clonal blood stem cell disorders.  \nMethods: From patient bone marrow or peripheral blood, we have isolated colonies grown from single blood stem cells/progenitors. Colony DNA will be analysed by whole-genome sequencing to build (or populate) a phylogenetic tree to determine clonal relationships and track stem cell contribution to mature blood cell production.  These data will also reveal disease-associated genomic features (mutational burden and mutational signatures) in haematopoietic cells.","abstract":"Background: Our recent study has made direct insight into the clonal dynamics of blood cell production in an unperturbed setting in a human. Using whole genome sequencing to track acquired somatic mutations, we were able to construct a phylogenetic tree of different stem and progenitor cells and used this tree to determine the dynamics of mature blood cell production in longitudinal samples. These data set the baseline for understanding population dynamics in abnormal haematopoiesis, and how malignant clones outcompete their normal counterparts to drive haematological malignancies.\nAim: This  study will measure population dynamics in abnormal human haematopoiesis in patients with clonal blood stem cell disorders.  \nMethods: From patient bone marrow or peripheral blood, we have isolated colonies grown from single blood stem cells/progenitors. Colony DNA will be analysed by whole-genome sequencing to build (or populate) a phylogenetic tree to determine clonal relationships and track stem cell contribution to mature blood cell production.  These data will also reveal disease-associated genomic features (mutational burden and mutational signatures) in haematopoietic cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-29T09:18:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003182","title":"Primary_sclerosing_cholangitis_project","description":"Primary sclerosing cholangitis (PSC) is a vasculitis affecting the hepatic arterial blood supply and may have an inflammatory or infectious aetiology. This is a proof-of concept study to use RNA seq to determine whether PSC is caused by infection or an inflammatory vasculitis.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Primary sclerosing cholangitis (PSC) is a vasculitis affecting the hepatic arterial blood supply and may have an inflammatory or infectious aetiology. This is a proof-of concept study to use RNA seq to determine whether PSC is caused by infection or an inflammatory vasculitis.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003183","title":"ImmunoAgeing_Longitudinal","description":"The objective is to establish whether immunosenescence is associated with the development of clonal haematopoiesis in a healthy ageing population. This will be addressed in collaboration with the European consortium running the ImmunoAgeing project (www.immunoageing.eu).   \nGenomic DNA derived from the peripheral blood of 394 individuals at 3-5 time-points over a 20-year period will be analysed. RNA bait pulldown (Agilent) will be used to perform targeted sequencing of genes known to be recurrently mutated in myeloid malignancies\nThe presence, size and nature of clonal haematopoiesis will be correlated with quantitative measures of immunosenescence.","abstract":"The objective is to establish whether immunosenescence is associated with the development of clonal haematopoiesis in a healthy ageing population. This will be addressed in collaboration with the European consortium running the ImmunoAgeing project (www.immunoageing.eu).   \nGenomic DNA derived from the peripheral blood of 394 individuals at 3-5 time-points over a 20-year period will be analysed. RNA bait pulldown (Agilent) will be used to perform targeted sequencing of genes known to be recurrently mutated in myeloid malignancies\nThe presence, size and nature of clonal haematopoiesis will be correlated with quantitative measures of immunosenescence.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-30T15:59:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003184","title":"Analysis of IDHwt-glioblastoma samples from paired primary and recurrent tumor samples","description":"IDHwt-glioblastomas rapidly recur after initial treatment. To study genetic evolution in glioblastoma, we analyzed whole genomes of 21 pairs of primary and recurrent tumor samples using next generation sequencing. In addition we sequenced RNA from 16 tumor pairs and a panel of 50 glioma-associated genes in tumor pairs from 43 patients (including 14 of the 21 patients included in the WGS discovery set). Glioblastoma subtypes were determined using 450k/EPIC methylation arrays.\n\nThis study was supported within the e:med program of the German Ministry of Education and Research (BMBF) by the collaborative research project ‘SYS-GLIO - Systems-based prediction of the biological and clinical behavior of gliomas’ (https://www.sys-med.de/de/demonstratoren/sys-glio/)\nThis study is part of the Heidelberg Center for Personalized Oncology - HIPO-043","abstract":"IDHwt-glioblastomas rapidly recur after initial treatment. To study genetic evolution in glioblastoma, we analyzed whole genomes of 21 pairs of primary and recurrent tumor samples using next generation sequencing. In addition we sequenced RNA from 16 tumor pairs and a panel of 50 glioma-associated genes in tumor pairs from 43 patients (including 14 of the 21 patients included in the WGS discovery set). Glioblastoma subtypes were determined using 450k/EPIC methylation arrays.\n\nThis study was supported within the e:med program of the German Ministry of Education and Research (BMBF) by the collaborative research project ‘SYS-GLIO - Systems-based prediction of the biological and clinical behavior of gliomas’ (https://www.sys-med.de/de/demonstratoren/sys-glio/)\nThis study is part of the Heidelberg Center for Personalized Oncology - HIPO-043","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-30T16:07:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003185","title":"BCR_repertoire_sequencing","description":"Isotype-specific B-cell receptor repertoire sequencing in six immune-mediated diseases at diagnosis and during therapy reveals an unexpectedly complex B-cell architecture, which may provide a platform for a better understanding of pathological mechanisms and treatment responses.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"B cells, and the antibodies they produce, have long been associated with autoimmune and inflammatory disease. We have developed improved technical approaches that permits increased analysis of the B cells in the context of disease. We have performed the first systematic comprehensive analysis to determine the global differences in B cell repertoire between autoimmune diseases and relationship to disease pathology in pre- and post-therapy patients. Isotype-specific B-cell receptor repertoire sequencing in six immune-mediated diseases at diagnosis and during therapy reveals an unexpectedly complex B-cell architecture, which may provide a platform for a better understanding of pathological mechanisms and treatment responses.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-31T08:59:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003186","title":"The molecular landscape of glioma in patients with Neurofibromatosis 1.","description":"Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome in which glioma is one of the most prominent tumor type. Gliomagenesis in NF1 results in heterogeneous spectrum of tumors, from low grade to high grade glioma, occurring during the entire patient lifespan. In this study, we present the molecular landscape of low- and high-grade glioma in children and adults affected by NF1 (NF1-glioma). 59 tumor samples from 56 NF1-glioma patients with 43 matched normal were profiled with Whole Exome Sequencing, DNA Methylation array (31 tumors) and RNA sequencing (29 tumors).","abstract":"Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome in which glioma is one of the most prominent tumor type. Gliomagenesis in NF1 results in heterogeneous spectrum of tumors, from low grade to high grade glioma, occurring during the entire patient lifespan. In this study, we present the molecular landscape of low- and high-grade glioma in children and adults affected by NF1 (NF1-glioma). 59 tumor samples from 56 NF1-glioma patients with 43 matched normal were profiled with Whole Exome Sequencing, DNA Methylation array (31 tumors) and RNA sequencing (29 tumors).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-08-31T12:48:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003187","title":"RNAseq___keratinocyte_cell_lines","description":"We are attempting to compare transcriptomic changes in keratinocyte cell lines between undifferentiated/differentiated cell states, as well as following stimulation with inflammatory cytokines. This will help prioritise hits generated from whole-genome CRISPR/Cas9 screens","abstract":"We are attempting to compare transcriptomic changes in keratinocyte cell lines between undifferentiated/differentiated cell states, as well as following stimulation with inflammatory cytokines. This will help prioritise hits generated from whole-genome CRISPR/Cas9 screens","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003188","title":"Genomic sequencing data of secondary glioblastoma","description":"Low-grade gliomas almost invariably progress into secondary glioblastoma (sGBM) with limited therapeutic option and poorly understood mechanism. By studying mutational landscape of 188 sGBMs, we find significant enrichment of TP53 mutations, somatic hypermutation, MET-exon-14-skipping (METex14), PTPRZ1-MET (ZM) fusions, and MET amplification. Strikingly, METex14 that frequently co-occurs with ZM fusion presents in ~14% of sGBM cases with significant worse prognosis. Subsequent studies show that METex14 predicts glioma progression by stabilizing MET activity. Furthermore, we described a new MET kinase inhibitor, PLB-1001, which demonstrates remarkable potency in selectively inhibiting MET-altered tumor cells in different preclinical models. Importantly, this compound also shows superior blood-brain barrier permeability, and is subsequently applied in a Phase I clinical trial that enrolls MET-altered chemo-resistant glioma patients. Encouragingly, PLB-1001 achieves partial response in at least two advanced sGBM patients with rarely significant side effects, underscoring the clinical potential for precisely treating gliomas using this novel therapy.","abstract":"Low-grade gliomas almost invariably progress into secondary glioblastoma (sGBM) with limited therapeutic option and poorly understood mechanism. By studying mutational landscape of 188 sGBMs, we find significant enrichment of TP53 mutations, somatic hypermutation, MET-exon-14-skipping (METex14), PTPRZ1-MET (ZM) fusions, and MET amplification. Strikingly, METex14 that frequently co-occurs with ZM fusion presents in ~14% of sGBM cases with significant worse prognosis. Subsequent studies show that METex14 predicts glioma progression by stabilizing MET activity. Furthermore, we described a new MET kinase inhibitor, PLB-1001, which demonstrates remarkable potency in selectively inhibiting MET-altered tumor cells in different preclinical models. Importantly, this compound also shows superior blood-brain barrier permeability, and is subsequently applied in a Phase I clinical trial that enrolls MET-altered chemo-resistant glioma patients. Encouragingly, PLB-1001 achieves partial response in at least two advanced sGBM patients with rarely significant side effects, underscoring the clinical potential for precisely treating gliomas using this novel therapy.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003189","title":"TFH_human","description":"The project aims to identify the heterogeneity of human T follicular regulatory cells from different anatomic locations, as well as distinctive features of their transcriptome, using follicular helper T cells and conventional regulatory T cells as reference populations.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The project aims to identify the heterogeneity of human T follicular regulatory cells from different anatomic locations, as well as distinctive features of their transcriptome, using follicular helper T cells and conventional regulatory T cells as reference populations.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003190","title":"Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing","description":"Accurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding of tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, and open source computational methods. Using DLP+, we have generated a resource of 51,926 single-cell genomes and matched cell images from diverse cell types including cell lines, xenografts, and diagnostic samples with limited material. From this resource we have defined variation in mitotic mis-segregation rates across tissue types and genotypes. Analysis of matched genomic and image measurements revealed correlations between cellular morphology and genome ploidy states. Aggregation of cells sharing copy number profiles allowed for calculation of single-nucleotide resolution clonal genotypes and inference of clonal phylogenies and avoided the limitations of bulk deconvolution. Finally, joint analysis over the above features defined clone-specific chromosomal aneuploidy in polyclonal populations.","abstract":"Accurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding of tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, and open source computational methods. Using DLP+, we have generated a resource of 51,926 single-cell genomes and matched cell images from diverse cell types including cell lines, xenografts, and diagnostic samples with limited material. From this resource we have defined variation in mitotic mis-segregation rates across tissue types and genotypes. Analysis of matched genomic and image measurements revealed correlations between cellular morphology and genome ploidy states. Aggregation of cells sharing copy number profiles allowed for calculation of single-nucleotide resolution clonal genotypes and inference of clonal phylogenies and avoided the limitations of bulk deconvolution. Finally, joint analysis over the above features defined clone-specific chromosomal aneuploidy in polyclonal populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-05T00:30:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003191","title":"Oesophageal_Adenocarcinoma_Organoid_10x","description":"10x Sequencing of 6 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical rescetion of the tumour. All model derivations took place with the CGaP facility in Sanger.  This 10x data will be combined with other sequencing data in order to generate accurate reference cancer genomes.","abstract":"There is complex interplay between underlying genetic sequence and epigenetic factors, however this interplay is still illusive. Massively reconstructed cancer genomes can be used in order to better understand this relationship. Six oesophageal adenocarcinoma organoids will be sequenced using long read sequencing technologies and will be profiled for a range of epigenetic marks. Combination of genetic and epigenetic data will allow the thorough characterisation of reference cancer genomes and will provide novel insights into mechanisms of gene regulation.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-05T14:39:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003192","title":"10X_Single_Cell_transcriptome_analysis_of_the_human_heart","description":"The aim of this project is to profile human heart on a single-cell level. Cardiac human tissue will be sampled from both adult and fetal donors and will be processed for 10X single cell and single nuclei RNA sequencing and spatial transcriptomics.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The aim of this project is to profile human heart on a single-cell level. Cardiac human tissue will be sampled from both adult and fetal donors and will be processed for 10X single cell and single nuclei RNA sequencing and spatial transcriptomics.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003193","title":"Improving CLL Vγ9Vδ2-T cell fitness for cellular therapy by ex vivo activation and ibrutinib","description":"We studied whether Vγ9Vδ2-T cells can exploited as autologous effector lymphocytes in chronic lymphocytic leukemia (CLL). Healthy controls (HC) Vγ9Vδ2-T cells were activated by and had potent cytolytic activity against CLL cells, however CLL-derived Vγ9Vδ2-T cells proved dysfunctional with respect to effector cytokine production and cytotxicity. Dysfunction of Vγ9Vδ2-T cells was reversible upon activation with autologous monocyte-derived dendritic cells (mODCs). RNA sequencing confirmed that Vγ9Vδ2-T cells from CLL patients have a transcriptional profile that is distinct from HC Vγ9Vδ2-T cells prior to ex vivo expansion, although the profile after ex vivo expansion is similar between CLL and HC Vγ9Vδ2-T cells. Gene expression profiling implicated alterations in both synapse formation and exhaustion as conceivable contributors to compromised Vγ9Vδ2-T cell function in CLL patients. Taken together, CLL-mediated dysfunction of autologous Vγ9Vδ2-T cells is fully reversible, resulting in potent cytotoxicity towards CLL cells.","abstract":"We studied whether Vγ9Vδ2-T cells can exploited as autologous effector lymphocytes in chronic lymphocytic leukemia (CLL). Healthy controls (HC) Vγ9Vδ2-T cells were activated by and had potent cytolytic activity against CLL cells, however CLL-derived Vγ9Vδ2-T cells proved dysfunctional with respect to effector cytokine production and cytotxicity. Dysfunction of Vγ9Vδ2-T cells was reversible upon activation with autologous monocyte-derived dendritic cells (mODCs). RNA sequencing confirmed that Vγ9Vδ2-T cells from CLL patients have a transcriptional profile that is distinct from HC Vγ9Vδ2-T cells prior to ex vivo expansion, although the profile after ex vivo expansion is similar between CLL and HC Vγ9Vδ2-T cells. Gene expression profiling implicated alterations in both synapse formation and exhaustion as conceivable contributors to compromised Vγ9Vδ2-T cell function in CLL patients. Taken together, CLL-mediated dysfunction of autologous Vγ9Vδ2-T cells is fully reversible, resulting in potent cytotoxicity towards CLL cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-07T08:54:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003194","title":"Methylation_profiles_in_cancer_induced_mouse_liver_tumours","description":"Human cancers arise through the combined effect of environmental exposures and endogenous mutagenesis resulting from factors such as replication stress and metabolism. Here, we will address the question of how exposure to a wide variety of exogenous agents can shape epigenomic architecture. Specifically, we will characterize the methylation profiles of dozens of suspected/known human carcinogens used to induce hundreds of mouse liver tumours and then explore the changes of the methylation profiles following carcinogen exposure. Other aspects of tumour biology will also be explored, such as mutational signatures, driver genes, and the effect that carcinogens have on the copy number landscape and profile of structural variants found in tumours.","abstract":"Human cancers arise through the combined effect of environmental exposures and endogenous mutagenesis resulting from factors such as replication stress and metabolism. Here, we will address the question of how exposure to a wide variety of exogenous agents can shape epigenomic architecture. Specifically, we will characterize the methylation profiles of dozens of suspected/known human carcinogens used to induce hundreds of mouse liver tumours and then explore the changes of the methylation profiles following carcinogen exposure. Other aspects of tumour biology will also be explored, such as mutational signatures, driver genes, and the effect that carcinogens have on the copy number landscape and profile of structural variants found in tumours.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003195","title":"Low frequency and rare coding variation contributes to multiple sclerosis risk","description":"Multiple sclerosis is a common, complex neurological disease, where almost 20% of risk heritability can be attributed to common genetic variants, including &gt;230 identified by genome-wide association studies. Multiple strands of evidence suggest that the majority of the remaining heritability is also due to the additive effects of individual variants, rather than epistatic interactions between these variants, or mutations exclusive to individual families. Here, we show in 68,379 cases and controls that as much as 5% of this heritability is explained by low-frequency variation in gene coding sequence. We identify four novel genes driving MS risk independently of common variant signals, which highlight a key role for regulatory T cell homeostasis and regulation, IFNγ biology and NFκB signaling in MS pathogenesis.","abstract":"Multiple sclerosis is a common, complex neurological disease, where almost 20% of risk heritability can be attributed to common genetic variants, including &gt;230 identified by genome-wide association studies. Multiple strands of evidence suggest that the majority of the remaining heritability is also due to the additive effects of individual variants, rather than epistatic interactions between these variants, or mutations exclusive to individual families. Here, we show in 68,379 cases and controls that as much as 5% of this heritability is explained by low-frequency variation in gene coding sequence. We identify four novel genes driving MS risk independently of common variant signals, which highlight a key role for regulatory T cell homeostasis and regulation, IFNγ biology and NFκB signaling in MS pathogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-08T18:41:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003196","title":"Exome-sequencing of paired docetaxel sensitive and resistant triple-negative breast cancer","description":"Taxane-based regimens constitute the most common therapeutic option in patients with triple-negative breast cancer (TNBC). Resistance to treatment often arises although the molecular mechanisms responsible for this process are unknown. To unravel chemoresistance mechanisms, exome sequencing was performed on matched docetaxel sensitive and resistant TNBC patient-derived xenografts (PDX).","abstract":"Taxane-based regimens constitute the most common therapeutic option in patients with triple-negative breast cancer (TNBC). Resistance to treatment often arises although the molecular mechanisms responsible for this process are unknown. To unravel chemoresistance mechanisms, exome sequencing was performed on matched docetaxel sensitive and resistant TNBC patient-derived xenografts (PDX).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003197","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__pancreas_LCM_","description":"Samples prepared by LCM - 5 cases for pilot study. Bulk DNA not available.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute (Illumina HiSeqX, 40X and 20X depth respectively). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \n\nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-10T12:38:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003198","title":"NEVER USED (was intended to be Mucosal Melanoma, before it became a dataset under the existing Melanoma parent study in ega-box-11)","description":"NEVER USED","abstract":"NEVER USED","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003199","title":"Genome-wide association study of cervical cancer in East Asian populations","description":"The development of cervical cancer is initiated by human papillomavirus (HPV) infection, and involves both viral and host genetic factors.  Genome-wide association studies (GWAS) of cervical cancer have identified associations in the HLA locus and two loci outside HLA, but the principal genes that control infection and pathogenesis have not been identified.  In the present study, we performed GWAS of cervical cancer in East Asian populations, involving 2609 cases and 4712 controls in the discovery stage, 1461 cases and 3295 controls in the follow-up stage.","abstract":"The development of cervical cancer is initiated by human papillomavirus (HPV) infection, and involves both viral and host genetic factors.  Genome-wide association studies (GWAS) of cervical cancer have identified associations in the HLA locus and two loci outside HLA, but the principal genes that control infection and pathogenesis have not been identified.  In the present study, we performed GWAS of cervical cancer in East Asian populations, involving 2609 cases and 4712 controls in the discovery stage, 1461 cases and 3295 controls in the follow-up stage.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-11T08:18:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003200","title":"Exploiting evolutionary steering in cancer therapy","description":"Drug resistance, mediated by intra-tumour heterogeneity and clonal evolution, is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at the cost of increased sensitivity to another due to so-called evolutionary trade-offs. This weakness can be exploited in the clinic using an approach called ‘evolutionary herding’ that aims at controlling the tumour cell population to delay or prevent resistance. However, model systems able to recapitulate cancer evolution experimentally are lacking and current in vitro techniques based on small populations, re-plating and escalating dose, are unsuitable to develop evolutionary herding strategies. We present a novel methodology for evolutionary herding in vitro and ex vivo using patient-derived organoids. Our approach is based on a combination of single-cell barcoding, very large populations of 108-109 cells grown without re-plating, realistic high drug doses, time-course monitoring of cancer clones, and mathematical modelling of tumour evolutionary dynamics. We demonstrate evolutionary herding in non-small cell lung cancer in vitro and in patient-derived colorectal cancer organoids (PDO). We show that herding causes controlled evolutionary bottlenecks that lead to collateral sensitivity. Through genomic analysis, we were also able to determine the mechanisms that drive such sensitivity. Our approach allows modelling evolutionary trade-offs experimentally to test patient-specific evolutionary herding strategies that can be translated into the clinic to control treatment resistance.","abstract":"Drug resistance, mediated by intra-tumour heterogeneity and clonal evolution, is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at the cost of increased sensitivity to another due to so-called evolutionary trade-offs. This weakness can be exploited in the clinic using an approach called ‘evolutionary herding’ that aims at controlling the tumour cell population to delay or prevent resistance. However, model systems able to recapitulate cancer evolution experimentally are lacking and current in vitro techniques based on small populations, re-plating and escalating dose, are unsuitable to develop evolutionary herding strategies. We present a novel methodology for evolutionary herding in vitro and ex vivo using patient-derived organoids. Our approach is based on a combination of single-cell barcoding, very large populations of 108-109 cells grown without re-plating, realistic high drug doses, time-course monitoring of cancer clones, and mathematical modelling of tumour evolutionary dynamics. We demonstrate evolutionary herding in non-small cell lung cancer in vitro and in patient-derived colorectal cancer organoids (PDO). We show that herding causes controlled evolutionary bottlenecks that lead to collateral sensitivity. Through genomic analysis, we were also able to determine the mechanisms that drive such sensitivity. Our approach allows modelling evolutionary trade-offs experimentally to test patient-specific evolutionary herding strategies that can be translated into the clinic to control treatment resistance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-11T14:19:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003201","title":"Whole genome and RNAseq analysis of pediatric osteosarcoma","description":"Integrative analysis whole genome sequencing and RNA-seq in pediatric osteosarcoma primary tumors and patient derived tumor xenografts.","abstract":"Integrative analysis whole genome sequencing and RNA-seq in pediatric osteosarcoma primary tumors and patient derived tumor xenografts.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-11T16:18:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003202","title":"The_Genome_Diversity_in_Africa_project__building_a_HLA_data_resource_for_Africa","description":"Very little is known about the genetic diversity of the Human Leukocyte Antigen (HLA) region in African populations, and the availability of sequences from African individuals from this region are limited in existing HLA databases. Using single molecule real-time (SMRT) sequencing (PacBio)  and Illumina Myseq sequencing we aim to generate HLA genomic regional sequences for up to 3,700 individuals from representative populations across Africa.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Very little is known about the genetic diversity of the Human Leukocyte Antigen (HLA) region in African populations, and the availability of sequences from African individuals from this region are limited in existing HLA databases. Using single molecule real-time (SMRT) sequencing (PacBio)  and Illumina Myseq sequencing we aim to generate HLA genomic regional sequences for up to 3,700 individuals from representative populations across Africa","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003203","title":"Hyperhaploid Multiple Myeloma","description":"Hyperhaploid multiple myeloma is a rare numerical aberration group defined by a range of 24-34 chromosomes which is associated with a poor prognosis.  Hyperhaploid samples were sequenced by either exome or targeted panel sequencing. Samples had a median of 13 monosomies (range 12-14), which in general were those not associated with trisomies in hyperdiploid samples.  The chromosomes traditionally trisomic in hyperdiploid myeloma were disomic in hyperhaploid myeloma with retention of heterodisomy.  We examined the hyperhaploid samples for frequently mutated genes and found that 9/9 (100%) hyperhaploid samples had a mutation in TP53, exceeding the overall rate of mutation in newly diagnosed patients (5.5%), indicating an oncogenic dependency in this group. All samples with TP53 mutation also had monosomy of chromosome 17, indicating bi-allelic inactivation of TP53.  As such, this high risk group is part of Double-Hit myeloma.\n\nDNA was obtained from either CD138+ cells from the bone marrow of multiple myeloma patients (tumor) or from stem cell harvests from the same patient (control). 100 ng of DNA was fragmented, end-repaired, and adapters ligated using the HyperPlus kit (KAPA Biosystems).  After PCR amplification the libraries were hybridized with probes against either the entire exome (MedExome, Nimblegen) or a targeted panel of 140 genes using SeqCap reagents (Nimblegen). Hybridized libraries underwent further amplification before being sequenced on a NextSeq500 (Illumina) using 75 bp paired end reads.","abstract":"Hyperhaploid multiple myeloma is a rare numerical aberration group defined by a range of 24-34 chromosomes which is associated with a poor prognosis.  Hyperhaploid samples were sequenced by either exome or targeted panel sequencing. Samples had a median of 13 monosomies (range 12-14), which in general were those not associated with trisomies in hyperdiploid samples.  The chromosomes traditionally trisomic in hyperdiploid myeloma were disomic in hyperhaploid myeloma with retention of heterodisomy.  We examined the hyperhaploid samples for frequently mutated genes and found that 9/9 (100%) hyperhaploid samples had a mutation in TP53, exceeding the overall rate of mutation in newly diagnosed patients (5.5%), indicating an oncogenic dependency in this group. All samples with TP53 mutation also had monosomy of chromosome 17, indicating bi-allelic inactivation of TP53.  As such, this high risk group is part of Double-Hit myeloma.\n\nDNA was obtained from either CD138+ cells from the bone marrow of multiple myeloma patients (tumor) or from stem cell harvests from the same patient (control). 100 ng of DNA was fragmented, end-repaired, and adapters ligated using the HyperPlus kit (KAPA Biosystems).  After PCR amplification the libraries were hybridized with probes against either the entire exome (MedExome, Nimblegen) or a targeted panel of 140 genes using SeqCap reagents (Nimblegen). Hybridized libraries underwent further amplification before being sequenced on a NextSeq500 (Illumina) using 75 bp paired end reads.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-11T16:57:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003204","title":"DEPRECATED Integration of Genomic and Transcriptional Features in Pancreatic Cancer Reveals Increased Cell Cycle Progression in Metastases","description":"We integrated clinical, genomic and transcriptomic data from 216 primaries and 95 metastases from 285 patients to characterize progression of pancreatic ductal adenocarcinoma (PDAC). Driver gene alterations, and mutational and expression-based signatures were mostly preserved; discordances implied Halstedian tumour spread. Cell cycle progression increased with sequential inactivation of tumour suppressors, yet remained higher in metastases, perhaps driven by cell cycle regulatory gene missenses. Half of the cases were hypoxic by expression markers, overlapping with molecular subtypes. Paired tumour heterogeneity showed truncations, inversions and translocations are conserved and therefore likely driver events. Multiple PDAC arising synchronously and metachronously in the same pancreas were actually intra-parenchymal metastases, not independent primary tumours. Established clinical co-variates dominated survival analyses, though cell cycle progression, hypoxia and paired tumour heterogeneity may inform clinical practice.","abstract":"We integrated clinical, genomic and transcriptomic data from 216 primaries and 95 metastases from 285 patients to characterize progression of pancreatic ductal adenocarcinoma (PDAC). Driver gene alterations, and mutational and expression-based signatures were mostly preserved; discordances implied Halstedian tumour spread. Cell cycle progression increased with sequential inactivation of tumour suppressors, yet remained higher in metastases, perhaps driven by cell cycle regulatory gene missenses. Half of the cases were hypoxic by expression markers, overlapping with molecular subtypes. Paired tumour heterogeneity showed truncations, inversions and translocations are conserved and therefore likely driver events. Multiple PDAC arising synchronously and metachronously in the same pancreas were actually intra-parenchymal metastases, not independent primary tumours. Established clinical co-variates dominated survival analyses, though cell cycle progression, hypoxia and paired tumour heterogeneity may inform clinical practice.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003205","title":"Transcriptional_analysis_of_myeloid_cells_from_lung","description":"To capture the full heterogeneity of the myeloid population of cells within the lung, myeloid cells at different stages will be obtained by FACS-sorting using antibody panel designed for myeloid cells. The samples from tumour and non-tumour lung tissue from different patients will be processed using the 10x Genomics platform. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"To capture the full heterogeneity of the myeloid population of cells within the lung, myeloid cells at different stages will be obtained by FACS-sorting using antibody panel designed for myeloid cells. The samples from tumour and non-tumour lung tissue from different patients will be processed using the 10x Genomics platform.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003206","title":"Inference of transcription factor binding from cell-free DNA enables tumor subtype prediction and early detection","description":"Deregulation of transcription factors (TFs) is an important driver of tumorigenesis, but non-invasive assays for assessing transcription factor activity are lacking. We Here we developed and validated a minimally invasive method for assessing TF activity based on cell-free DNA sequencing and nucleosome footprint analysis. We analyzed whole genome sequencing data for &gt;1,000 cell-free DNA samples from cancer patients and healthy controls using a newly developed bioinformatics pipeline developed by us that infers accessibility of TF binding sites from cell-free DNA fragmentation patterns. We observe patient-specific as well as tumor-specific patterns, including accurate prediction of tumor subtypes in prostate cancer, with important clinical implications for the management of patients. Furthermore, we show that cell-free DNA TF profiling is capable of detection of early-stage colorectal carcinomas. Our approach for mapping tumor-specific transcription factor binding in vivo based on blood samples makes a key part of the noncoding genome amenable to clinical analysis.","abstract":"Deregulation of transcription factors (TFs) is an important driver of tumorigenesis, but non-invasive assays for assessing transcription factor activity are lacking. We Here we developed and validated a minimally invasive method for assessing TF activity based on cell-free DNA sequencing and nucleosome footprint analysis. We analyzed whole genome sequencing data for &gt;1,000 cell-free DNA samples from cancer patients and healthy controls using a newly developed bioinformatics pipeline developed by us that infers accessibility of TF binding sites from cell-free DNA fragmentation patterns. We observe patient-specific as well as tumor-specific patterns, including accurate prediction of tumor subtypes in prostate cancer, with important clinical implications for the management of patients. Furthermore, we show that cell-free DNA TF profiling is capable of detection of early-stage colorectal carcinomas. Our approach for mapping tumor-specific transcription factor binding in vivo based on blood samples makes a key part of the noncoding genome amenable to clinical analysis.","study_type":"Other","pubmed_ids":[31604930],"external_links":null,"is_released":true,"released_date":"2018-09-12T10:53:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003207","title":"Whole exome sequencing of 76 individuals with familial atrial fibrillation","description":"We investigated genetic background of familial and early onset atrial fibrillation (AF) with the aim of identify genes involved in atrial fibrillation pathology and are highly predisposing risk factors. We performed whole exome sequencing on 24 families where three or more family members suffered from AF.","abstract":"We investigated genetic background of familial and early onset atrial fibrillation (AF) with the aim of identify genes involved in atrial fibrillation pathology and are highly predisposing risk factors. We performed whole exome sequencing on 24 families where three or more family members suffered from AF.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-12T14:00:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003208","title":"early onset lone atrial fibrillation case-control study","description":"Target sequencing W/ TruSight Cardio Sequencing Kit. 395 early onset lone AF cases and 375 controls. Sequencing was performed on Illumina NextSeq and HiSeq 2500 systems.395 early.","abstract":"Target sequencing W/ TruSight Cardio Sequencing Kit. 395 early onset lone AF cases and 375 controls. Sequencing was performed on Illumina NextSeq and HiSeq 2500 systems.395 early.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-12T15:36:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003209","title":"PAX5 biallelic genomic alterations define a novel subgroup of B cell precursor acute lymphoblastic leukemia","description":"Chromosomal rearrangements and specific aneuploidy patterns are initiating events and define subgroups in B cell precursor acute lymphoblastic leukemia (BCP-ALL). Here we analyzed 250 BCP-ALL cases and identified a novel subgroup (‘PAX5-plus’, n=19) by distinct DNA methylation and gene expression profiles. All patients in this subgroup harbored mutations in the B-lineage transcription factor PAX5, with p.P80R as hotspot. Mutations either affected two independent codons, consistent with compound heterozygosity, or suffered LOH predominantly through chromosome 9p aberrations. These biallelic events resulted in disruption of PAX5 transcriptional programs regulating B cell differentiation and tumor suppressor functions. Homozygous CDKN2A/B deletions and RAS activating hotspot mutations were highly enriched as cooperating events in the genomic profile of PAX5-plus ALL. Together this defined a specific pattern of triple alterations, exclusive to the novel subgroup. PAX5-plus ALL was observed in pediatric and adult patients. Although restricted by the limited sample size, a tendency for more favorable clinical outcome was observed with 10 of 12 adult PAX5-plus patients achieving long-term survival. PAX5-plus represents the first BCP-ALL subgroup defined by sequence alterations in contrast to gross chromosomal events and exemplifies how deregulated differentiation (PAX5), impaired cell cycle control (CDKN2A/B) together with sustained proliferative signaling (RAS) cooperatively drives leukemogenesis.","abstract":"Chromosomal rearrangements and specific aneuploidy patterns are initiating events and define subgroups in B cell precursor acute lymphoblastic leukemia (BCP-ALL). Here we analyzed 250 BCP-ALL cases and identified a novel subgroup (‘PAX5-plus’, n=19) by distinct DNA methylation and gene expression profiles. All patients in this subgroup harbored mutations in the B-lineage transcription factor PAX5, with p.P80R as hotspot. Mutations either affected two independent codons, consistent with compound heterozygosity, or suffered LOH predominantly through chromosome 9p aberrations. These biallelic events resulted in disruption of PAX5 transcriptional programs regulating B cell differentiation and tumor suppressor functions. Homozygous CDKN2A/B deletions and RAS activating hotspot mutations were highly enriched as cooperating events in the genomic profile of PAX5-plus ALL. Together this defined a specific pattern of triple alterations, exclusive to the novel subgroup. PAX5-plus ALL was observed in pediatric and adult patients. Although restricted by the limited sample size, a tendency for more favorable clinical outcome was observed with 10 of 12 adult PAX5-plus patients achieving long-term survival. PAX5-plus represents the first BCP-ALL subgroup defined by sequence alterations in contrast to gross chromosomal events and exemplifies how deregulated differentiation (PAX5), impaired cell cycle control (CDKN2A/B) together with sustained proliferative signaling (RAS) cooperatively drives leukemogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-13T08:11:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003210","title":"Somatic_mutation_and_clonal_evolution_in_the_human_bladder___WES","description":"In this study, we aim to characterise the landscape of mutation and clonal selection in the human bladder. The study includes whole exome sequencing of laser-dissected microbiopsies from the bladder. The samples utilised in this study will include urothelium from transplant donors with no history of bladder cancer and cystectomy specimens from patients with bladder cancer.","abstract":"In this study, we aim to characterise the landscape of mutation and clonal selection in the human bladder. The study includes whole exome sequencing of laser-dissected microbiopsies from the bladder. The samples utilised in this study will include urothelium from transplant donors with no history of bladder cancer and cystectomy specimens from patients with bladder cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003211","title":"Epigenetics/genetics of the patient-derived xenografts of pediatric T-cell leukemia","description":"Patient-derived xenografts (PDX) emerged as important tools to study leukemia biology and potential therapeutic regimens. Here, we compared cellular, molecular and developmental features of PDX-derived blasts with primary pediatric precursor T-cell acute leukemia (T-ALL) cells. The cells were collected at the times of initial diagnosis and relapse from 12 pediatric T-ALL patients. We analyzed the samples at the genomic level (whole genome sequencing (WGS), whole exome sequencing (WES), multiplex ligation probe amplification (MLPA), targeted sequencing) and the epigenetic level (DNA methylation, Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq)).","abstract":"Patient-derived xenografts (PDX) emerged as important tools to study leukemia biology and potential therapeutic regimens. Here, we compared cellular, molecular and developmental features of PDX-derived blasts with primary pediatric precursor T-cell acute leukemia (T-ALL) cells. The cells were collected at the times of initial diagnosis and relapse from 12 pediatric T-ALL patients. We analyzed the samples at the genomic level (whole genome sequencing (WGS), whole exome sequencing (WES), multiplex ligation probe amplification (MLPA), targeted sequencing) and the epigenetic level (DNA methylation, Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq)).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003212","title":"Structure and evolution of double minutes in diagnosis and relapse brain tumors","description":"Double minute chromosomes are extrachromosomal circular DNA fragments frequently found in brain tumors. To understand their evolution, we characterized the double minutes in paired diagnosis and relapse tumors from a pediatric high-grade glioma and four adult glioblastoma patients. We determined the full structures of the major double minutes using a novel approach combining multiple types of supporting genomic evidence. Among the double minutes identified in the pediatric tumor, only one carrying EGFR was maintained at high abundance in both samples, whereas two others were resent in only trace amounts at diagnosis but abundant at relapse, and the rest were found either in the relapse sample only or in the diagnosis sample only. For the EGFR-carrying double minutes, we found a secondary somatic deletion in all copies at relapse, after erlotinib treatment, but this was rare at diagnosis, suggesting potential resistance to the EGFR inhibitor. This mutation caused an in-frame RNA transcript to skip exon 16, a novel transcript absent in EST database and in about 700 brain tumors that we reviewed. We observed similar patterns involving longitudinal copy number shift of double minutes in another four pairs (diagnosis / relapse) of adult glioblastoma. Overall, in three of five paired tumor samples, we found that although the same oncogenes were amplified at diagnosis and relapse, they were amplified on different double minutes. Our results suggest that double minutes readily evolve, increasing tumor heterogeneity rapidly. Understanding patterns of double minute evolution can shed light on future therapeutic solutions to brain tumors carrying such variants.","abstract":"Double minute chromosomes are extrachromosomal circular DNA fragments frequently found in brain tumors. To understand their evolution, we characterized the double minutes in paired diagnosis and relapse tumors from a pediatric high-grade glioma and four adult glioblastoma patients. We determined the full structures of the major double minutes using a novel approach combining multiple types of supporting genomic evidence. Among the double minutes identified in the pediatric tumor, only one carrying EGFR was maintained at high abundance in both samples, whereas two others were resent in only trace amounts at diagnosis but abundant at relapse, and the rest were found either in the relapse sample only or in the diagnosis sample only. For the EGFR-carrying double minutes, we found a secondary somatic deletion in all copies at relapse, after erlotinib treatment, but this was rare at diagnosis, suggesting potential resistance to the EGFR inhibitor. This mutation caused an in-frame RNA transcript to skip exon 16, a novel transcript absent in EST database and in about 700 brain tumors that we reviewed. We observed similar patterns involving longitudinal copy number shift of double minutes in another four pairs (diagnosis / relapse) of adult glioblastoma. Overall, in three of five paired tumor samples, we found that although the same oncogenes were amplified at diagnosis and relapse, they were amplified on different double minutes. Our results suggest that double minutes readily evolve, increasing tumor heterogeneity rapidly. Understanding patterns of double minute evolution can shed light on future therapeutic solutions to brain tumors carrying such variants.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-14T16:05:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003213","title":"ERBB2/HER2 transmembrane and juxtamembrane domain mutations in cancer","description":"In this study, we identified several recurrent activating HER2 somatic mutations in transmembrane and juxtamembrane domain in multiple cancers and demonstrate that patients carryingthese mutations are candidates for anti-HER2 therapy. We have also identified a germline mutation in HER2 transmembrane domain.","abstract":"In this study, we identified several recurrent activating HER2 somatic mutations in transmembrane and juxtamembrane domain in multiple cancers and demonstrate that patients carryingthese mutations are candidates for anti-HER2 therapy. We have also identified a germline mutation in HER2 transmembrane domain.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-14T22:32:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003214","title":"FBSeq: RNA sequencing of human fetal brain.","description":"RNA sequencing of 120 human fetal brains (aged 12-19 post-conception weeks) was performed as part of a Medical Research Council (U.K.) funded project (MR/L010674/2) to investigate genetic effects on gene expression in the developing human brain and their role in neuropsychiatric disorders. Human fetal brain tissue from elective terminations of pregnancy was provided by the Human Developmental Biology Resource (HDBR) (http://www.hdbr.org), with ethical approval (#08/H0712/34), and with consent for use of fetal material for medical research provided by female donors. Total RNA was extracted from half of the available brain tissue from each fetus using Tri-Reagent and treated with TURBO DNase. RNA-Seq libraries were prepared using 1µg of purified total RNA and the Illumina TruSeq Stranded Total RNA Library Prep kit, following ribosomal RNA depletion. Libraries were sequenced on the Illumina HiSeq 2500 or HiSeq 4000 systems, generating at least 50 million read pairs per sample.","abstract":"RNA sequencing of 120 human fetal brains (aged 12-19 post-conception weeks) was performed as part of a Medical Research Council (U.K.) funded project (MR/L010674/2) to investigate genetic effects on gene expression in the developing human brain and their role in neuropsychiatric disorders. Human fetal brain tissue from elective terminations of pregnancy was provided by the Human Developmental Biology Resource (HDBR) (http://www.hdbr.org), with ethical approval (#08/H0712/34), and with consent for use of fetal material for medical research provided by female donors. Total RNA was extracted from half of the available brain tissue from each fetus using Tri-Reagent and treated with TURBO DNase. RNA-Seq libraries were prepared using 1µg of purified total RNA and the Illumina TruSeq Stranded Total RNA Library Prep kit, following ribosomal RNA depletion. Libraries were sequenced on the Illumina HiSeq 2500 or HiSeq 4000 systems, generating at least 50 million read pairs per sample.","study_type":"Other","pubmed_ids":[30419947],"external_links":null,"is_released":true,"released_date":"2018-09-15T13:00:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003215","title":"Single_cell_analysis_of_cytokine_induced_T_cell_states","description":"We isolated T cells from healthy platelet donors and cultured them in resting and stimulated conditions with addition of a range of cytokines. We performed scRNA sequencing to assess the variability of polarization in different cytokines treated  cells. \n\nCytokines affect T cell responses by polarising them to different phenotypes. Given that the inflammation and and autoimmune tissue distruction is driven by the local production of cytokines, we investigated cytokine induced changes in T cells by using a combination of immunological and genomics approaches. To characterize, the efficacy of cytokine induced porization, here we stimulated naive and memory CD4+ T cells in the presence of cytokine polarizing coctails and profiled single cell transcriptome five days following polarization.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We isolated T cells from healthy platelet donors and cultured them in resting and stimulated conditions with addition of a range of cytokines. We performed scRNA sequencing to assess the variability of polarization in different cytokines treated  cells. \n\nCytokines affect T cell responses by polarising them to different phenotypes. Given that the inflammation and and autoimmune tissue distruction is driven by the local production of cytokines, we investigated cytokine induced changes in T cells by using a combination of immunological and genomics approaches. To characterize, the efficacy of cytokine induced porization, here we stimulated naive and memory CD4+ T cells in the presence of cytokine polarizing coctails and profiled single cell transcriptome five days following polarization.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-18T13:46:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003216","title":"Multiple Sclerosis Replication Chip data (MS Chip)","description":"Genetic data typed with the MS Chip, designed by the International Multiple Sclerosis Genetics Consortium (IMSGC).","abstract":"Genetic data typed with the MS Chip, designed by the International Multiple Sclerosis Genetics Consortium (IMSGC).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-18T14:21:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003217","title":"Fecal Microbiota Transplantation for refractory immune checkpoint inhibitor-associated colitis","description":"We report the first case series of ICI associated colitis successfully treated with fecal microbiota transplantation (FMT), with reconstitution of the gut microbiome and a relative increase in the proportion of regulatory T cells (Tregs) within the colonic mucosa. These preliminary data provide evidence that modulation of the gut microbiome may abrogate ICI-associated colitis.","abstract":"We report the first case series of ICI associated colitis successfully treated with fecal microbiota transplantation (FMT), with reconstitution of the gut microbiome and a relative increase in the proportion of regulatory T cells (Tregs) within the colonic mucosa. These preliminary data provide evidence that modulation of the gut microbiome may abrogate ICI-associated colitis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-18T14:29:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003218","title":"Female South African Breast Cancer 166 Patients September 2018 Germ Line Illumina Trusight Cancer Panel","description":"Although selected variants in the BRCA1 and BRCA2 genes are commonly tested for in South African patients, a range of other high, medium and low penetrance genes play a role, and little is known about variants in in South African and African populations for these genes. We report on the occurrence of predicted and known deleterious variants in 94 cancer-related genes and 284 cancer variant-related positions in 166 black South African female breast cancer patients. A novel possibly pathogenic BRCA variants are described, together with pathogenic or possibly pathogenic variants in ATM, CHEK2, PALB2, APC, FANCG, PMS and XPC. The need for expanded studies in populations which are under-represented for genomic information is highlighted","abstract":"Although selected variants in the BRCA1 and BRCA2 genes are commonly tested for in South African patients, a range of other high, medium and low penetrance genes play a role, and little is known about variants in in South African and African populations for these genes. We report on the occurrence of predicted and known deleterious variants in 94 cancer-related genes and 284 cancer variant-related positions in 166 black South African female breast cancer patients. A novel possibly pathogenic BRCA variants are described, together with pathogenic or possibly pathogenic variants in ATM, CHEK2, PALB2, APC, FANCG, PMS and XPC. The need for expanded studies in populations which are under-represented for genomic information is highlighted","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003219","title":"Multiple Sclerosis ImmunoChip data","description":"The purpose of this study is to leverage the custom content of the ImmunoChip consortium; incorporating candidate loci from 12 autoimmune diseases, to both fine-map previously identified multiple sclerosis loci and identify new multiple sclerosis candidates.  As a fine-mapping array, both common and rare variation are included within a subset of ~180 candidate loci across the genome.","abstract":"The purpose of this study is to leverage the custom content of the ImmunoChip consortium; incorporating candidate loci from 12 autoimmune diseases, to both fine-map previously identified multiple sclerosis loci and identify new multiple sclerosis candidates.  As a fine-mapping array, both common and rare variation are included within a subset of ~180 candidate loci across the genome.","study_type":"Other","pubmed_ids":[24076602],"external_links":null,"is_released":true,"released_date":"2018-09-18T16:15:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003220","title":"Alternative splicing in Shh-MB","description":"We analyzed alternative splicing with Shh medulloblastoma. This dataset contains bam files of whole genome sequencing from 4 cases. Genomic DNA was isolated from both tumor and matched control specimens. We performed whole genome sequence on Illumina Hiseq.","abstract":"We analyzed alternative splicing with Shh medulloblastoma. This dataset contains bam files of whole genome sequencing from 4 cases. Genomic DNA was isolated from both tumor and matched control specimens. We performed whole genome sequence on Illumina Hiseq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-18T19:47:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003221","title":"Temporal stability of circulating microRNAs in human serum","description":"Circulating microRNA biomarkers for disease have been subject to extensive research.  However, insufficient consideration of variability in the healthy population has led to few markers achieving the performance necessary in independent follow-up studies to be taken forward to clinical practice. To investigate the natural variation of circulating microRNA over time, we performed small RNA sequencing in a longitudinal study of 66 women with no history of cancer, and determined the distribution and dynamics (via intraclass correlation coefficients, ICCs) of the miRNA profile over 3 time points sampled across 2-5 years. We also investigate abundances in circulation, as well as the impact of normalization, age, BMI, and other sample collection factors on microRNA measurements from small RNA sequencing.","abstract":"Circulating microRNA biomarkers for disease have been subject to extensive research.  However, insufficient consideration of variability in the healthy population has led to few markers achieving the performance necessary in independent follow-up studies to be taken forward to clinical practice. To investigate the natural variation of circulating microRNA over time, we performed small RNA sequencing in a longitudinal study of 66 women with no history of cancer, and determined the distribution and dynamics (via intraclass correlation coefficients, ICCs) of the miRNA profile over 3 time points sampled across 2-5 years. We also investigate abundances in circulation, as well as the impact of normalization, age, BMI, and other sample collection factors on microRNA measurements from small RNA sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-19T16:57:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003222","title":"Mutational landscape and temporal evolution during treatment of relapsed acute lymphoblastic leukemia","description":"To study the mechanisms of relapse in acute lymphoblastic leukemia, a leading cause of cancer-related death in children, we performed whole-genome sequencing of 103 diagnosis-relapse-germline trios and ultra-deep sequencing of 208 serial bone-marrow samples. Relapse-specific somatic alterations were significantly enriched in 12 genes (NR3C1/2, TP53, NT5C2, FPGS, CREBBP, MSH2/6, PMS2, WHSC1, and PRPS1/2) predominantly involved in drug response. The prevalence was 25%, 72% and 50% in very-early relapses (&lt;9 months from diagnosis), early (9-36 months) and late relapse (&gt;36 months), respectively. Two novel, relapse-specific mutational signatures likely gave rise to drug-resistant mutations, including NT5C2, PRPS1, and TP53 variants. Selective sweep and multi-lineage recurrence accounted for 53% and 26% of the relapses, respectively. Clonal composition evolved in response to chemotherapy including sequential acquisition of multiple resistance mutations. Resistant clones were detectable ~40 days prior to clinical relapse, suggesting ultra-deep sequencing as a means for early detection and therapeutic intervention.","abstract":"To study the mechanisms of relapse in acute lymphoblastic leukemia, a leading cause of cancer-related death in children, we performed whole-genome sequencing of 103 diagnosis-relapse-germline trios and ultra-deep sequencing of 208 serial bone-marrow samples. Relapse-specific somatic alterations were significantly enriched in 12 genes (NR3C1/2, TP53, NT5C2, FPGS, CREBBP, MSH2/6, PMS2, WHSC1, and PRPS1/2) predominantly involved in drug response. The prevalence was 25%, 72% and 50% in very-early relapses (&lt;9 months from diagnosis), early (9-36 months) and late relapse (&gt;36 months), respectively. Two novel, relapse-specific mutational signatures likely gave rise to drug-resistant mutations, including NT5C2, PRPS1, and TP53 variants. Selective sweep and multi-lineage recurrence accounted for 53% and 26% of the relapses, respectively. Clonal composition evolved in response to chemotherapy including sequential acquisition of multiple resistance mutations. Resistant clones were detectable ~40 days prior to clinical relapse, suggesting ultra-deep sequencing as a means for early detection and therapeutic intervention.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003223","title":"Multiple Myeloma Total Therapy trial patient sequencing","description":"The study of multiple myeloma (MM) genomics has identified many abnormalities that are associated with poor progression free survival (PFS) and overall survival (OS).  Copy number abnormalities have been extensively studied in many datasets with long follow-up, however, the prognostic impact of mutations have not been extensively studied and available datasets have generally had a relatively short follow-up. These analyses have identified a range of mutations that are associated with prognosis, making it important to extend these observations in larger studies with robust diagnostic technologies. Samples from newly diagnosed MM patients enrolled in Total Therapy trials (n=225) were sequenced on a targeted panel consisting of 140 genes and additional regions of interest for copy number, as well as tiling of the Ig and MYC loci for detection of translocations.  Samples were sequenced to a median depth of 452x using 2x75 bp paired end reads.  Reads were aligned to hg19 and mutations called using Strelka and filtered with fpfilter. Translocations were called by Manta, and copy number determined by read depth ratio and loss of heterozygosity comparison with a patient matched non-tumor sample.\n\nDNA was obtained from either CD138+ cells from the bone marrow of multiple myeloma patients (tumor) or from stem cell harvests or peripheral blood cells from the same patient (control). 100 ng of DNA was fragmented, end-repaired, and adapters ligated using the HyperPlus kit (KAPA Biosystems).  After PCR amplification the libraries were hybridized with probes against either a targeted panel consisting of 140 genes and chromosomal regions (Nimblegen) using SeqCap reagents (Nimblegen). Hybridized libraries underwent further amplification before being sequenced on a NextSeq500 (Illumina) using 75 bp paired end reads\n\nThere are 450 (225 tumor and 225 germline) samples in this study. 263 are available as part of this dataset. The remaining 187 are available with dataset accession id EGAD00001004117.","abstract":"The study of multiple myeloma (MM) genomics has identified many abnormalities that are associated with poor progression free survival (PFS) and overall survival (OS).  Copy number abnormalities have been extensively studied in many datasets with long follow-up, however, the prognostic impact of mutations have not been extensively studied and available datasets have generally had a relatively short follow-up. These analyses have identified a range of mutations that are associated with prognosis, making it important to extend these observations in larger studies with robust diagnostic technologies. Samples from newly diagnosed MM patients enrolled in Total Therapy trials (n=225) were sequenced on a targeted panel consisting of 140 genes and additional regions of interest for copy number, as well as tiling of the Ig and MYC loci for detection of translocations.  Samples were sequenced to a median depth of 452x using 2x75 bp paired end reads.  Reads were aligned to hg19 and mutations called using Strelka and filtered with fpfilter. Translocations were called by Manta, and copy number determined by read depth ratio and loss of heterozygosity comparison with a patient matched non-tumor sample.\n\nDNA was obtained from either CD138+ cells from the bone marrow of multiple myeloma patients (tumor) or from stem cell harvests or peripheral blood cells from the same patient (control). 100 ng of DNA was fragmented, end-repaired, and adapters ligated using the HyperPlus kit (KAPA Biosystems).  After PCR amplification the libraries were hybridized with probes against either a targeted panel consisting of 140 genes and chromosomal regions (Nimblegen) using SeqCap reagents (Nimblegen). Hybridized libraries underwent further amplification before being sequenced on a NextSeq500 (Illumina) using 75 bp paired end reads\n\nThere are 450 (225 tumor and 225 germline) samples in this study. 263 are available as part of this dataset. The remaining 187 are available with dataset accession id EGAD00001004117.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-19T22:13:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003224","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___GI___TPS___WES","description":"Somatic mutations (burdens and signatures) and clonal dynamics in normal human tissues from the gastrointestinal tract of individuals with tumour predisposition syndromes and DNA damage repair defects.","abstract":"The aim of this project is to investigate somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the study of normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to identify and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-20T13:04:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003225","title":"Genomic profiling of esthesioneuroblastoma","description":"We performed whole exome and whole genome sequencing on a cohort of esthesioneurblastoma to understand the genetic underpinnings of this neoplasm.","abstract":"We performed whole exome and whole genome sequencing on a cohort of esthesioneurblastoma to understand the genetic underpinnings of this neoplasm.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-20T21:28:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003226","title":"WGS of breast cancer diagnosed during pregnancy and matched control","description":"The aim of this study was to compare the mutational landscape of breast cancer diagnosed during pregnancy (BCP) and breast cancer from age/stage non-pregnant patients (controls). We present whole genome sequencing data (Illumina HiSeq X ten platform) of tumor and matched normal tissues from 35 BCP patients and 20 controls. This work provides important novel biological insights and a unique resource to study the biology of breast cancer in young women and how pregnancy could modulate tumor biology.","abstract":"The aim of this study was to compare the mutational landscape of breast cancer diagnosed during pregnancy (BCP) and breast cancer from age/stage non-pregnant patients (controls). We present whole genome sequencing data (Illumina HiSeq X ten platform) of tumor and matched normal tissues from 35 BCP patients and 20 controls. This work provides important novel biological insights and a unique resource to study the biology of breast cancer in young women and how pregnancy could modulate tumor biology.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003227","title":"Whole Exome Sequencing in Multiple Myeloma","description":"By whole exome sequencing (WES) our group observed the accumulation of mutations in receptor tyrosine kinases (RTKs), adhesion molecules and their effectors and developed a signaling network that was affected by at least one mutation in almost 100% of MM patients and by more than one mutation in around 50% of MM patients which we decided to call inter- and intra-individual pathway redundancy. Interestingly, the extension of our WES dataset to 67 primary MM samples with correspond normal tissue which were collected at the Medizinische Klinik and Poliklinik II in Würzburg within the frame of the CRU216 has tentatively led to the designation of three molecular subgroups based on their mutation profile: \"adhesion only\", \"adhesion &amp; downstream\" and \"RTK &amp; adhesion &amp; downstream","abstract":"By whole exome sequencing (WES) our group observed the accumulation of mutations in receptor tyrosine kinases (RTKs), adhesion molecules and their effectors and developed a signaling network that was affected by at least one mutation in almost 100% of MM patients and by more than one mutation in around 50% of MM patients which we decided to call inter- and intra-individual pathway redundancy. Interestingly, the extension of our WES dataset to 67 primary MM samples with correspond normal tissue which were collected at the Medizinische Klinik and Poliklinik II in Würzburg within the frame of the CRU216 has tentatively led to the designation of three molecular subgroups based on their mutation profile: \"adhesion only\", \"adhesion &amp; downstream\" and \"RTK &amp; adhesion &amp; downstream","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-24T12:09:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003228","title":"Genomic landscape of oral cancers (Illumina WGS)","description":"Human papillomavirus (HPV) is a necessary but insufficient cause of a subset of oral squamous cell carcinomas (OSCC) that is increasing markedly in frequency. To identify contributory, secondary genetic alterations in these cancers, we used comprehensive genomics methods to compare 149 HPV-positive and 335 HPV-negative OSCC tumor/normal pairs. Different behavioral risk factors underlying the two OSCC types were reflected in distinctive genomic mutational signatures. In HPV-positive OSCC, the signatures of APOBEC cytosine deaminase editing, associated with anti-viral immunity, were strongly linked to overall mutational burden. By contrast, in HPV-negative OSCC, T&gt;C substitutions in the sequence context 5’-ATN-3’ correlated with tobacco exposure. Universal expression of HPV E6*1 and E7 oncogenes was a sine qua non of HPV-positive OSCC. Significant enrichment of somatic mutations was confirmed or newly identified in PIK3CA, KMT2D, FGFR3, FBXW7, DDX3X, PTEN, TRAF3, RB1, CYLD, RIPK4, ZNF750, EP300, CASZ1, TAF5, RBL1, IFNGR1 and NFKBIA. Of these, many affect host pathways already targeted by HPV oncoproteins, including the p53 and pRB pathways, or disrupt host defenses against viral infections, including interferon and nuclear factor-B signaling. Frequent copy number changes were associated with concordant changes in gene expression. Chr. 11q (including CCND1) and 14q (including DICER1 and AKT1) were recurrently lost in HPV-positive OSCC, in contrast to their gains in HPV-negative OSCC. High-ranking variant allele fractions implicated ZNF750, PIK3CA and EP300 mutations as candidate driver events in HPV-positive cancers. We conclude that virus-host interactions cooperatively shape the unique genetic features of these cancers, distinguishing them from their HPV-negative counterparts.","abstract":"Human papillomavirus (HPV) is a necessary but insufficient cause of a subset of oral squamous cell carcinomas (OSCC) that is increasing markedly in frequency. To identify contributory, secondary genetic alterations in these cancers, we used comprehensive genomics methods to compare 149 HPV-positive and 335 HPV-negative OSCC tumor/normal pairs. Different behavioral risk factors underlying the two OSCC types were reflected in distinctive genomic mutational signatures. In HPV-positive OSCC, the signatures of APOBEC cytosine deaminase editing, associated with anti-viral immunity, were strongly linked to overall mutational burden. By contrast, in HPV-negative OSCC, T&gt;C substitutions in the sequence context 5’-ATN-3’ correlated with tobacco exposure. Universal expression of HPV E6*1 and E7 oncogenes was a sine qua non of HPV-positive OSCC. Significant enrichment of somatic mutations was confirmed or newly identified in PIK3CA, KMT2D, FGFR3, FBXW7, DDX3X, PTEN, TRAF3, RB1, CYLD, RIPK4, ZNF750, EP300, CASZ1, TAF5, RBL1, IFNGR1 and NFKBIA. Of these, many affect host pathways already targeted by HPV oncoproteins, including the p53 and pRB pathways, or disrupt host defenses against viral infections, including interferon and nuclear factor-B signaling. Frequent copy number changes were associated with concordant changes in gene expression. Chr. 11q (including CCND1) and 14q (including DICER1 and AKT1) were recurrently lost in HPV-positive OSCC, in contrast to their gains in HPV-negative OSCC. High-ranking variant allele fractions implicated ZNF750, PIK3CA and EP300 mutations as candidate driver events in HPV-positive cancers. We conclude that virus-host interactions cooperatively shape the unique genetic features of these cancers, distinguishing them from their HPV-negative counterparts.","study_type":"Other","pubmed_ids":[30563911],"external_links":null,"is_released":true,"released_date":"2018-09-24T21:40:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003229","title":"Both in vivo colon tissues and patient-derived organoids were performed WGS and WES to estimate the copy number variants and point mutations","description":"Patient-derived organoid is a recently developed powerful system to study the molecular mechanisms of cancers, especially for the colorectal cancer, one of most prevalent cancer worldwide. However, the similarities and differences of gene expression patterns of the organoids in culture and corresponding cancer cells in vivo were still largely unexplored. Here, we established patient-derived organoid lines from CRC patients that closely recapitulate in vivo molecular diversity of human colorectal cancer. We performed single-cell RNA-Seq for pairwise samples from seven patients for both organoids in culture and their corresponding tissues in vivo. We found that normal-derived organoid exhibited tumor-like feature at transcriptome but remained normal at genome. Tumor-derived organoid not only recapitulate the in vivo tumor transcriptome and genome features, but also keep the p-TME state and maintain the crosstalk between cancer epithelial cell and mesenchymal cell at early passage. We also found that PPAR antagonist can inhibit the proliferation of colon cancer.","abstract":"Patient-derived organoid is a recently developed powerful system to study the molecular mechanisms of cancers, especially for the colorectal cancer, one of most prevalent cancer worldwide. However, the similarities and differences of gene expression patterns of the organoids in culture and corresponding cancer cells in vivo were still largely unexplored. Here, we established patient-derived organoid lines from CRC patients that closely recapitulate in vivo molecular diversity of human colorectal cancer. We performed single-cell RNA-Seq for pairwise samples from seven patients for both organoids in culture and their corresponding tissues in vivo. We found that normal-derived organoid exhibited tumor-like feature at transcriptome but remained normal at genome. Tumor-derived organoid not only recapitulate the in vivo tumor transcriptome and genome features, but also keep the p-TME state and maintain the crosstalk between cancer epithelial cell and mesenchymal cell at early passage. We also found that PPAR antagonist can inhibit the proliferation of colon cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003230","title":"Integrative epigenomic characterisation of glioblastoma (HIPO project 016)","description":"Cancer Master Regulators (MRs) are proteins that define the cell state of cancer cells via transcriptional regulation. As the epigenome of a cell is highly correlated with the transcriptome, it therefore follows that transcription factor (TF) proteins acting as cancer MRs are also likely to regulate the epigenome, which itself will  affect the activity of TF MRs. Human adult glioblastoma (GB) consists of four methylation subtypes. However, the epigenetic landscape of each subtype remains largely uncharacterised, as well as the interplay between MR activity and the epigenome. Here we present an integrated epigenomic characterisation and MR identification of GB subtypes using a cohort of 60 deeply characterised adult GBs, identifying SOX10 as a master regulator of the RTK_I subtype, and whose loss causes a transition to the MES subtype. We describe differences between subtypes in their methylation and chromatin landscapes at base-pair resolution, including a novel CpG Island  Methylator Phenotype (CIMP)-like  pattern of hypermethylation targeting normal brain bivalent promoters in the RTK_II subtype. We identified 10 consensus MRs using orthogonal analyses of superenhancers and gene  co- expression networks, and we show  that the removal of SOX10 in an RTK_I model results in MR activation, phenotypic, and epigenetic changes characteristic of the MES subtype. Our analysis is the first comprehensive comparative analysis of GB subtype epigenomes, and illustrates the interplay between epigenetics, gene  expression and MR activity.(HIPO project 016)","abstract":"Cancer Master Regulators (MRs) are proteins that define the cell state of cancer cells via transcriptional regulation. As the epigenome of a cell is highly correlated with the transcriptome, it therefore follows that transcription factor (TF) proteins acting as cancer MRs are also likely to regulate the epigenome, which itself will  affect the activity of TF MRs. Human adult glioblastoma (GB) consists of four methylation subtypes. However, the epigenetic landscape of each subtype remains largely uncharacterised, as well as the interplay between MR activity and the epigenome. Here we present an integrated epigenomic characterisation and MR identification of GB subtypes using a cohort of 60 deeply characterised adult GBs, identifying SOX10 as a master regulator of the RTK_I subtype, and whose loss causes a transition to the MES subtype. We describe differences between subtypes in their methylation and chromatin landscapes at base-pair resolution, including a novel CpG Island  Methylator Phenotype (CIMP)-like  pattern of hypermethylation targeting normal brain bivalent promoters in the RTK_II subtype. We identified 10 consensus MRs using orthogonal analyses of superenhancers and gene  co- expression networks, and we show  that the removal of SOX10 in an RTK_I model results in MR activation, phenotypic, and epigenetic changes characteristic of the MES subtype. Our analysis is the first comprehensive comparative analysis of GB subtype epigenomes, and illustrates the interplay between epigenetics, gene  expression and MR activity.(HIPO project 016)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003231","title":"Gain of function DNMT3A mutations cause microcephalic dwarfism and hypermethylation of Polycomb-regulated regions","description":"DNA methylation and Polycomb are key factors in the establishment of vertebrate cellular identity and fate. Here we report de novo missense mutations in DNMT3A, encoding the DNA methyltransferase DNMT3A, that cause microcephalic dwarfism, a hypocellular disorder of extreme global growth failure. Substitutions in the PWWP domain abrogate binding to the histone modifications H3K36me2/3, and alter DNA methylation in patient cells. Polycomb-associated DNA methylation canyons/valleys, hypomethylated domains encompassing developmental genes, become methylated with concomitant depletion of H3K27me3 and H3K4me3 bivalent marks. Such de novo DNA methylation occurs during differentiation of Dnmt3aW326R pluripotent cells in vitro, and is also evident in Dnmt3aW326R/+ dwarf mice. We therefore propose that the interaction of the DNMT3A PWWP domain with H3K36me2/3 normally limits DNA methylation of polycomb-marked regions.  Our findings implicate the interplay between DNA methylation and polycomb at key developmental regulators as a determinant of organism size in mammals.","abstract":"DNA methylation and Polycomb are key factors in the establishment of vertebrate cellular identity and fate. Here we report de novo missense mutations in DNMT3A, encoding the DNA methyltransferase DNMT3A, that cause microcephalic dwarfism, a hypocellular disorder of extreme global growth failure. Substitutions in the PWWP domain abrogate binding to the histone modifications H3K36me2/3, and alter DNA methylation in patient cells. Polycomb-associated DNA methylation canyons/valleys, hypomethylated domains encompassing developmental genes, become methylated with concomitant depletion of H3K27me3 and H3K4me3 bivalent marks. Such de novo DNA methylation occurs during differentiation of Dnmt3aW326R pluripotent cells in vitro, and is also evident in Dnmt3aW326R/+ dwarf mice. We therefore propose that the interaction of the DNMT3A PWWP domain with H3K36me2/3 normally limits DNA methylation of polycomb-marked regions.  Our findings implicate the interplay between DNA methylation and polycomb at key developmental regulators as a determinant of organism size in mammals.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-25T13:49:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003232","title":"Gain of function DNMT3A mutations cause microcephalic dwarfism and hypermethylation of Polycomb-regulated regions","description":"DNA methylation and Polycomb are key factors in the establishment of vertebrate cellular identity and fate. Here we report de novo missense mutations in DNMT3A, encoding the DNA methyltransferase DNMT3A, that cause microcephalic dwarfism, a hypocellular disorder of extreme global growth failure. Substitutions in the PWWP domain abrogate binding to the histone modifications H3K36me2/3, and alter DNA methylation in patient cells. Polycomb-associated DNA methylation canyons/valleys, hypomethylated domains encompassing developmental genes, become methylated with concomitant depletion of H3K27me3 and H3K4me3 bivalent marks. Such de novo DNA methylation occurs during differentiation of Dnmt3aW326R pluripotent cells in vitro, and is also evident in Dnmt3aW326R/+ dwarf mice. We therefore propose that the interaction of the DNMT3A PWWP domain with H3K36me2/3 normally limits DNA methylation of polycomb-marked regions.  Our findings implicate the interplay between DNA methylation and polycomb at key developmental regulators as a determinant of organism size in mammals.","abstract":"DNA methylation and Polycomb are key factors in the establishment of vertebrate cellular identity and fate. Here we report de novo missense mutations in DNMT3A, encoding the DNA methyltransferase DNMT3A, that cause microcephalic dwarfism, a hypocellular disorder of extreme global growth failure. Substitutions in the PWWP domain abrogate binding to the histone modifications H3K36me2/3, and alter DNA methylation in patient cells. Polycomb-associated DNA methylation canyons/valleys, hypomethylated domains encompassing developmental genes, become methylated with concomitant depletion of H3K27me3 and H3K4me3 bivalent marks. Such de novo DNA methylation occurs during differentiation of Dnmt3aW326R pluripotent cells in vitro, and is also evident in Dnmt3aW326R/+ dwarf mice. We therefore propose that the interaction of the DNMT3A PWWP domain with H3K36me2/3 normally limits DNA methylation of polycomb-marked regions.  Our findings implicate the interplay between DNA methylation and polycomb at key developmental regulators as a determinant of organism size in mammals.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-25T14:29:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003233","title":"Molecular Classification of Lymph Node Metastases Subtypes Predict for Survival in Head and Neck Cancer","description":null,"abstract":"Using clustering of RNA and miRNA profiles, we described three novel subtypes of lymph node metastases in Human Papillomavirus-negative Head and Neck cancers.   One lymph node metastasis-specific subtype had a 10-fold higher risk of locoregional recurrence in head and neck cancers and predicted for worse disease control and/or survival in breast cancers and melanomas. Identification of this aggressive subtype will enable better risk stratification of patients and the selection of patients for treatment escalation.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-26T08:30:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003234","title":"An exome sequencing approach to defining the genetic risk factors for Achilles tendinopathy","description":"Musculoskeletal soft tissue injuries are complex phenotypes. Case control association studies using the candidate gene approach have predominantly been used to identify risk loci for these injuries. However, the ability to identify all risk conferring variants using this approach alone is unlikely. Therefore, this study aimed to define the genetic profile of these injuries using whole exome sequencing and a customized analysis pipeline. The exomes of ten exemplar asymptomatic controls and ten exemplar cases with Achilles tendinopathy were individually sequenced using a platform that included the coverage of the untranslated regions and miRBase miRNA genes. These results provide a proof of concept for the use of a customized pipeline for the exploration of a larger genomic dataset. This approach, using previous research to guide a targeted analysis of the data has generated new genetic signatures in the biology of musculoskeletal soft tissue injuries.","abstract":"Musculoskeletal soft tissue injuries are complex phenotypes. Case control association studies using the candidate gene approach have predominantly been used to identify risk loci for these injuries. However, the ability to identify all risk conferring variants using this approach alone is unlikely. Therefore, this study aimed to define the genetic profile of these injuries using whole exome sequencing and a customized analysis pipeline. The exomes of ten exemplar asymptomatic controls and ten exemplar cases with Achilles tendinopathy were individually sequenced using a platform that included the coverage of the untranslated regions and miRBase miRNA genes. These results provide a proof of concept for the use of a customized pipeline for the exploration of a larger genomic dataset. This approach, using previous research to guide a targeted analysis of the data has generated new genetic signatures in the biology of musculoskeletal soft tissue injuries.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-26T07:05:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003235","title":"Oncogenic fate conversion by PRDM16s causes acute myeloid leukemia","description":"Oncogenic mutations confer aberrant replicative capacity to cells with little or no replicative capacity, generating cancer stem cells that perpetuate the tumor through extensive self-replication and differentiation blockade. However, whether oncogenes disrupt the cellular identity ofcancer stem cell by altering the developmental potential is unknown. Fate conversion has been demonstrated by ectopic expression of master transcriptional regulators, such as PU.1 and C/EBP alpha that confers myeloid cell fate to other cell types, and PRDM16 that confers brown adipose fate to white adipocytes or myoblasts. Here we show that a transcriptional regulator overexpressed in human myeloid malignancies, PRDM16s, causes oncogenic fate conversion, by transforming cells fated to form platelets and erythrocytes into myeloid leukemia-initiating cells (LICs). Prdm16s expression in hematopoietic progenitor cells caused a myelodysplastic syndrome (MDS)-like disease that progressed to acute myelogenous leukemia (AML). The myeloid diseases caused by Prdm16s exhibited expansion of megakaryocyte-erythroid progenitors (MEPs) but not granulocyte-macrophage progenitors. MEPs from Prdm16s-induced leukemia possessed LIC potential, and expression of Prdm16s in normal MEPs was sufficient to convert them to myeloid LICs and blocked megakaryocytic/erythroid potential. Prdm16s induced the expression of myeloid master regulators, including PU.1 and C/EBP alpha, by interacting with their super enhancers. Ablation of myeloid master regulators attenuated the myeloid potential and reinstalled the megakaryocytic/erythroid potential of leukemic-MEPs in mouse models and in human AML with PRDM16 rearrangement. Our study demonstrates that oncogenic Prdm16 expression converts the fate of MEPs to a malignant myeloid fate by activating myeloid master transcription factors.","abstract":"Oncogenic mutations confer aberrant replicative capacity to cells with little or no replicative capacity, generating cancer stem cells that perpetuate the tumor through extensive self-replication and differentiation blockade. However, whether oncogenes disrupt the cellular identity ofcancer stem cell by altering the developmental potential is unknown. Fate conversion has been demonstrated by ectopic expression of master transcriptional regulators, such as PU.1 and C/EBP alpha that confers myeloid cell fate to other cell types, and PRDM16 that confers brown adipose fate to white adipocytes or myoblasts. Here we show that a transcriptional regulator overexpressed in human myeloid malignancies, PRDM16s, causes oncogenic fate conversion, by transforming cells fated to form platelets and erythrocytes into myeloid leukemia-initiating cells (LICs). Prdm16s expression in hematopoietic progenitor cells caused a myelodysplastic syndrome (MDS)-like disease that progressed to acute myelogenous leukemia (AML). The myeloid diseases caused by Prdm16s exhibited expansion of megakaryocyte-erythroid progenitors (MEPs) but not granulocyte-macrophage progenitors. MEPs from Prdm16s-induced leukemia possessed LIC potential, and expression of Prdm16s in normal MEPs was sufficient to convert them to myeloid LICs and blocked megakaryocytic/erythroid potential. Prdm16s induced the expression of myeloid master regulators, including PU.1 and C/EBP alpha, by interacting with their super enhancers. Ablation of myeloid master regulators attenuated the myeloid potential and reinstalled the megakaryocytic/erythroid potential of leukemic-MEPs in mouse models and in human AML with PRDM16 rearrangement. Our study demonstrates that oncogenic Prdm16 expression converts the fate of MEPs to a malignant myeloid fate by activating myeloid master transcription factors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-26T07:56:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003236","title":"Discovery of new fusion transcripts in a cohort of pediatric solid cancers at relapse","description":"This study aims to dissect further the complexity of fusion landscape in recurrent pediatric cancers. A retrospective study on RNA-sequencing data of 48 pediatric patients at relapse with different malignancies was conducted in order to detect and validate several fusions and predict their probable oncogenic potential and targetability. We obtained a high validation rate of 90% of selected candidates which will serve both clinical and research needs to detect and prioritize experimental validation studies leading to the development of new therapeutic options.","abstract":"This study aims to dissect further the complexity of fusion landscape in recurrent pediatric cancers. A retrospective study on RNA-sequencing data of 48 pediatric patients at relapse with different malignancies was conducted in order to detect and validate several fusions and predict their probable oncogenic potential and targetability. We obtained a high validation rate of 90% of selected candidates which will serve both clinical and research needs to detect and prioritize experimental validation studies leading to the development of new therapeutic options.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-26T12:18:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003237","title":"Genomic landscape of oral cancers (Illumina RNA-Seq)","description":"Human papillomavirus (HPV) is a necessary but insufficient cause of a subset of oral squamous cell carcinomas (OSCC) that is increasing markedly in frequency. To identify contributory, secondary genetic alterations in these cancers, we used comprehensive genomics methods to compare 149 HPV-positive and 335 HPV-negative OSCC tumor/normal pairs. Different behavioral risk factors underlying the two OSCC types were reflected in distinctive genomic mutational signatures. In HPV-positive OSCC, the signatures of APOBEC cytosine deaminase editing, associated with anti-viral immunity, were strongly linked to overall mutational burden. By contrast, in HPV-negative OSCC, T&gt;C substitutions in the sequence context 5’-ATN-3’ correlated with tobacco exposure. Universal expression of HPV E6*1 and E7 oncogenes was a sine qua non of HPV-positive OSCC. Significant enrichment of somatic mutations was confirmed or newly identified in PIK3CA, KMT2D, FGFR3, FBXW7, DDX3X, PTEN, TRAF3, RB1, CYLD, RIPK4, ZNF750, EP300, CASZ1, TAF5, RBL1, IFNGR1 and NFKBIA. Of these, many affect host pathways already targeted by HPV oncoproteins, including the p53 and pRB pathways, or disrupt host defenses against viral infections, including interferon and nuclear factor-B signaling. Frequent copy number changes were associated with concordant changes in gene expression. Chr. 11q (including CCND1) and 14q (including DICER1 and AKT1) were recurrently lost in HPV-positive OSCC, in contrast to their gains in HPV-negative OSCC. High-ranking variant allele fractions implicated ZNF750, PIK3CA and EP300 mutations as candidate driver events in HPV-positive cancers. We conclude that virus-host interactions cooperatively shape the unique genetic features of these cancers, distinguishing them from their HPV-negative counterparts.","abstract":"Human papillomavirus (HPV) is a necessary but insufficient cause of a subset of oral squamous cell carcinomas (OSCC) that is increasing markedly in frequency. To identify contributory, secondary genetic alterations in these cancers, we used comprehensive genomics methods to compare 149 HPV-positive and 335 HPV-negative OSCC tumor/normal pairs. Different behavioral risk factors underlying the two OSCC types were reflected in distinctive genomic mutational signatures. In HPV-positive OSCC, the signatures of APOBEC cytosine deaminase editing, associated with anti-viral immunity, were strongly linked to overall mutational burden. By contrast, in HPV-negative OSCC, T&gt;C substitutions in the sequence context 5’-ATN-3’ correlated with tobacco exposure. Universal expression of HPV E6*1 and E7 oncogenes was a sine qua non of HPV-positive OSCC. Significant enrichment of somatic mutations was confirmed or newly identified in PIK3CA, KMT2D, FGFR3, FBXW7, DDX3X, PTEN, TRAF3, RB1, CYLD, RIPK4, ZNF750, EP300, CASZ1, TAF5, RBL1, IFNGR1 and NFKBIA. Of these, many affect host pathways already targeted by HPV oncoproteins, including the p53 and pRB pathways, or disrupt host defenses against viral infections, including interferon and nuclear factor-B signaling. Frequent copy number changes were associated with concordant changes in gene expression. Chr. 11q (including CCND1) and 14q (including DICER1 and AKT1) were recurrently lost in HPV-positive OSCC, in contrast to their gains in HPV-negative OSCC. High-ranking variant allele fractions implicated ZNF750, PIK3CA and EP300 mutations as candidate driver events in HPV-positive cancers. We conclude that virus-host interactions cooperatively shape the unique genetic features of these cancers, distinguishing them from their HPV-negative counterparts.","study_type":"Other","pubmed_ids":[30563911],"external_links":null,"is_released":true,"released_date":"2018-09-26T17:55:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003238","title":"Fibroblast heterogeneity drives metastatic spread in breast cancer through distinct mechanisms","description":"The major cause of death among breast cancer patients is metastatic dissemination, suggesting that understanding the mechanisms driving this process remains an unmet medical need. Here, by concomitantly using 5 markers, we identify 4 Carcinoma-Associated Fibroblasts (CAF) subsets in primary tumors and corresponding metastatic lymph nodes (LN). Two CAF subsets, called CAF-S1 and CAF-S4, correlate with the proportion of cancer cells in invaded LN and exert distinct functions in tumor cell spread. CAF-S1 promote cancer cell migration and initiates an epithelial to mesenchymal transition through a CXCL12 / TGFb positive loop. For their part, the highly contractile CAF-S4 foster cancer cell motility and invasion in 3-dimensional matrix via Notch pathway activation. Finally, CAF-S1 and CAF-S4 accumulation in LN is a new prognostic factor at diagnostic, independent of breast cancer subtypes and LN status, strengthening the validity of our findings in human breast cancer pathophysiology.","abstract":"The major cause of death among breast cancer patients is metastatic dissemination, suggesting that understanding the mechanisms driving this process remains an unmet medical need. Here, by concomitantly using 5 markers, we identify 4 Carcinoma-Associated Fibroblasts (CAF) subsets in primary tumors and corresponding metastatic lymph nodes (LN). Two CAF subsets, called CAF-S1 and CAF-S4, correlate with the proportion of cancer cells in invaded LN and exert distinct functions in tumor cell spread. CAF-S1 promote cancer cell migration and initiates an epithelial to mesenchymal transition through a CXCL12 / TGFb positive loop. For their part, the highly contractile CAF-S4 foster cancer cell motility and invasion in 3-dimensional matrix via Notch pathway activation. Finally, CAF-S1 and CAF-S4 accumulation in LN is a new prognostic factor at diagnostic, independent of breast cancer subtypes and LN status, strengthening the validity of our findings in human breast cancer pathophysiology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-09-28T16:16:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003239","title":"The malaria-protective human glycophorin structural variant DUP4 shows somatic mosaicism and association with hemoglobin levels","description":"Glycophorin A and glycophorin B are red blood cell surface proteins that are both receptors for the parasite Plasmodium falciparum, which is the principal cause of malaria in sub-Saharan Africa. DUP4 is a complex structural genomic variant that carries extra copies of a glycophorin A - glycophorin B fusion gene, and has a dramatic effect on malaria risk by reducing the risk of severe malaria by up to 40% Using fiber-FISH and Illumina sequencing, we validate the structural arrangement of the glycophorin locus in the DUP4 variant, and reveal somatic variation in copy number of the glycophorin A- glycophorin B fusion gene. By developing a simple, specific, PCR-based assay for DUP4 we show the DUP4 variant reaches a frequency of 13% in a malaria-endemic village in south-eastern Tanzania. We genotype a substantial proportion of that village and demonstrate an association of DUP4 genotype with hemoglobin levels, a phenotype related to malaria, using a family-based association test. Taken together, we show that DUP4 is a complex structural variant that may be susceptible to somatic variation, and show that it is associated with a malarial-related phenotype in a non-hospitalizedlongitudinally-followed population.","abstract":"Glycophorin A and glycophorin B are red blood cell surface proteins that are both receptors for the parasite Plasmodium falciparum, which is the principal cause of malaria in sub-Saharan Africa. DUP4 is a complex structural genomic variant that carries extra copies of a glycophorin A - glycophorin B fusion gene, and has a dramatic effect on malaria risk by reducing the risk of severe malaria by up to 40% Using fiber-FISH and Illumina sequencing, we validate the structural arrangement of the glycophorin locus in the DUP4 variant, and reveal somatic variation in copy number of the glycophorin A- glycophorin B fusion gene. By developing a simple, specific, PCR-based assay for DUP4 we show the DUP4 variant reaches a frequency of 13% in a malaria-endemic village in south-eastern Tanzania. We genotype a substantial proportion of that village and demonstrate an association of DUP4 genotype with hemoglobin levels, a phenotype related to malaria, using a family-based association test. Taken together, we show that DUP4 is a complex structural variant that may be susceptible to somatic variation, and show that it is associated with a malarial-related phenotype in a non-hospitalizedlongitudinally-followed population.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-01T15:21:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003240","title":"C1R cell line  transcriptome analysis","description":null,"abstract":"Chimeric antigen receptor anti-CD19 (CAR19)-T cell immunotherapy-induced clinical remissions in CD19+ B cell lymphomas are often short-lived. We tested whether CAR19-engineering of the CD1d-restricted invariant NKT (iNKT) cells would result in enhanced anti-lymphoma activity. CAR19-iNKT cells co-operatively activated by CD1d- and CAR19-CD19-dependent interactions are more effective than CAR19-T cells against CD1d-expressing lymphomas in vitro and in vivo. The swifter in vivo anti-lymphoma activity of CAR19-iNKT cells and their enhanced ability to eradicate brain lymphomas underpinned an improved tumor-free and overall survival. CD1d transcriptional de-repression by all-trans retinoic acid results in further enhanced cytotoxicity of CAR19-iNKT cells against CD19+ chronic lymphocytic leukemia cells. Thus, iNKT cells are a highly efficient platform for CAR-based immunotherapy of lymphomas and possibly other CD1d-expressing cancers.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003241","title":"CAR-iNKT, CAR T primary cells   transcriptome analysis","description":null,"abstract":"Chimeric antigen receptor anti-CD19 (CAR19)-T cell immunotherapy-induced clinical remissions in CD19+ B cell lymphomas are often short-lived. We tested whether CAR19-engineering of the CD1d-restricted invariant NKT (iNKT) cells would result in enhanced anti-lymphoma activity. CAR19-iNKT cells co-operatively activated by CD1d- and CAR19-CD19-dependent interactions are more effective than CAR19-T cells against CD1d-expressing lymphomas in vitro and in vivo. The swifter in vivo anti-lymphoma activity of CAR19-iNKT cells and their enhanced ability to eradicate brain lymphomas underpinned an improved tumor-free and overall survival. CD1d transcriptional de-repression by all-trans retinoic acid results in further enhanced cytotoxicity of CAR19-iNKT cells against CD19+ chronic lymphocytic leukemia cells. Thus, iNKT cells are a highly efficient platform for CAR-based immunotherapy of lymphomas and possibly other CD1d-expressing cancers","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003242","title":"Genomic DNA of tumor tissues, adjacent normal tissues, and peripheral blood were extracted using QIAamp DNA mini Kit (QIAGEN, cat. #51306)","description":"Although genomic instability, epigenetic abnormality, and gene expression dysregulation are hallmarks of colorectal cancer, these features have not been simultaneously analyzed at single cell resolution. Using optimized single cell multiomics sequencing together with multiregional sampling of the primary tumor, lymphatic and distant metastases, we provide insights beyond intratumoral heterogeneity. Genome wide DNA methylation levels were relatively consistent within a single genetic sublineage. The genome-wide DNA demethylation patterns of cancer cells were consistent in all 10 sequenced patients. The cancer cells’ DNA demethylation degrees clearly correlated with the densities of the heterochromatin-associated histone modification H3K9me3 of normal tissue, and those of repetitive element Long Interspersed Nuclear Element 1. Our work demonstrates the feasibility of reconstructing genetic lineages, and tracing their epigenomic and transcriptomic dynamics with single cell multiomics sequencing.","abstract":"Although genomic instability, epigenetic abnormality, and gene expression dysregulation are hallmarks of colorectal cancer, these features have not been simultaneously analyzed at single cell resolution. Using optimized single cell multiomics sequencing together with multiregional sampling of the primary tumor, lymphatic and distant metastases, we provide insights beyond intratumoral heterogeneity. Genome wide DNA methylation levels were relatively consistent within a single genetic sublineage. The genome-wide DNA demethylation patterns of cancer cells were consistent in all 10 sequenced patients. The cancer cells’ DNA demethylation degrees clearly correlated with the densities of the heterochromatin-associated histone modification H3K9me3 of normal tissue, and those of repetitive element Long Interspersed Nuclear Element 1. Our work demonstrates the feasibility of reconstructing genetic lineages, and tracing their epigenomic and transcriptomic dynamics with single cell multiomics sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-02T03:48:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003243","title":"Ultraviolet radiation-induced DNA damage is prognostic for outcome in melanoma","description":"The melanoma genomic landscape is dominated by ultraviolet radiation (UVR)-induced mutations. Their significance in disease progression is unknown, so we classify 419 melanomas by mutation signatures and identify 10 recurrently mutated UVR signature genes that predict improved patient survival. We validate these findings in primary melanomas and in mice. Finally, we show that this signature is imprinted by short wavelength UVR, and that only 4 UVR exposures are sufficient to accelerate melanomagenesis.","abstract":"The melanoma genomic landscape is dominated by ultraviolet radiation (UVR)-induced mutations. Their significance in disease progression is unknown, so we classify 419 melanomas by mutation signatures and identify 10 recurrently mutated UVR signature genes that predict improved patient survival. We validate these findings in primary melanomas and in mice. Finally, we show that this signature is imprinted by short wavelength UVR, and that only 4 UVR exposures are sufficient to accelerate melanomagenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003244","title":"A mechanistic classification of clinical phenotypes in neuroblastoma","description":"Clinical courses of the pediatric tumor neuroblastoma range from fatal progression to spontaneous regression. To gain insights into the pathogenesis of these divergent subtypes, we performed massively parallel sequencing of 416 pretreatment neuroblastomas and assessed telomere maintenance mechanisms in 208/416 cases. We observed that telomere maintenance and mutations in RAS or p53 pathway genes strongly affected disease courses. Fatal outcome occurred only in the presence of telomere maintenance, whereas patients whose tumors lacked such mechanisms had excellent outcome. In patients with telomere maintenance-positive tumors, survival was dramatically inferior when additional RAS/p53 pathway mutations were present. By contrast, spontaneous regression occurred both in the presence and absence of RAS/p53 pathway mutations in patients with telomere maintenance-negative tumors. Together, our data provide a precise mechanistic classification of clinical neuroblastoma phenotypes based on telomere maintenance mechanisms and genetic alterations of the tumor.","abstract":"Clinical courses of the pediatric tumor neuroblastoma range from fatal progression to spontaneous regression. To gain insights into the pathogenesis of these divergent subtypes, we performed massively parallel sequencing of 416 pretreatment neuroblastomas and assessed telomere maintenance mechanisms in 208/416 cases. We observed that telomere maintenance and mutations in RAS or p53 pathway genes strongly affected disease courses. Fatal outcome occurred only in the presence of telomere maintenance, whereas patients whose tumors lacked such mechanisms had excellent outcome. In patients with telomere maintenance-positive tumors, survival was dramatically inferior when additional RAS/p53 pathway mutations were present. By contrast, spontaneous regression occurred both in the presence and absence of RAS/p53 pathway mutations in patients with telomere maintenance-negative tumors. Together, our data provide a precise mechanistic classification of clinical neuroblastoma phenotypes based on telomere maintenance mechanisms and genetic alterations of the tumor.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-02T14:02:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003245","title":"Single-cell TCR sequencing of gluten-specific T cells","description":null,"abstract":"To examine the T-cell receptors specific  to DQ2.5-glia-α1a and DQ2.5-glia-ω1 epitopes in Celiac disease, we isolated single CD4+ T cells from blood , gut biopsies  or T-cell lines generated from gut biopsies  using HLA-DQ2.5 tetramers and determined the sequences of rearranged TCRa and TCRb gene pairs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-02T17:41:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003246","title":"Enhanced detection of circulating tumor DNA by fragment size analysis","description":null,"abstract":"Existing methods to improve detection of ctDNA have focused on sensitivity of mutation detection and not the biological properties of plasma cell-free DNA (cfDNA). We hypothesized that differences in fragment lengths of circulating DNA could be exploited to enhance sensitivity for detecting the presence of ctDNA and for non-invasive genomic analysis of cancer. We surveyed ctDNA fragment sizes in 344 plasma samples from 200 cancer patients using low-pass whole-genome sequencing (0.4×). To establish the size distribution of mutant ctDNA, tumor-guided personalized deep sequencing was performed in in 19 patients. We detected enrichment of ctDNA in fragment sizes between 90–150 bp, and developed methods for in vitro and in silico size selection of these fragments. Selecting fragments between 90–150 bp improved detection of tumor DNA by more than 2-fold median enrichment in &gt;95% of cases, and by more than 4-fold enrichment in &gt;10% of cases. Analysis of size-selected cfDNA identified clinically actionable mutations and copy number alterations that were otherwise not detected. Identification of patients with advanced cancer was improved by predictive models integrating fragment length and copy number analysis of cfDNA with AUC&gt;0.99 compared to AUC&lt;0.80 without fragmentation features. Increased detection of cfDNA from patients with glioma, renal and pancreatic cancer patients was achieved with AUC&gt;0.91, compared to AUC&lt;0.5 without fragmentation features. Fragment-size analysis and selective sequencing of specific fragment sizes can boost ctDNA detection, and could be an alternative to deeper mutation sequencing for clinical applications, earlier diagnosis and to study tumor biology.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003247","title":"Characterizing the immune and genome landscapes for osteosarcoma","description":"Osteosarcoma have heavily rearranged genomes and moderate tumor mutation burden, which suggests that the patients may express neoantigens that could be targeted by immune cells.  To characterize the immunogenomic landscape of this disease, we performed genome, transcriptome, immune and proteomic profiling of 48 patients comprised largely of relapsed and metastatic cases from both pediatric and adult patients.","abstract":"Osteosarcoma have heavily rearranged genomes and moderate tumor mutation burden, which suggests that the patients may express neoantigens that could be targeted by immune cells.  To characterize the immunogenomic landscape of this disease, we performed genome, transcriptome, immune and proteomic profiling of 48 patients comprised largely of relapsed and metastatic cases from both pediatric and adult patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-02T18:43:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003248","title":"Epigenetics/genetics of the patient-derived xenografts of pediatric T-cell leukemia","description":"We compared 12 pediatric T cell acute lymphoblastic leukemias collected at initial diagnosis and relapse with their corresponding PDX models. The analysis was performed on genomic level (whole genome sequencing (WGS), whole exome sequencing (WES), multiplex ligation probe amplification (MLPA), targeted sequencing) and the epigenetic level (DNA methylation, Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq)). In sum, this study underlines the remarkable genomic stability, and for the first time documents the preservation of the epigenomic landscape in T-ALL-derived PDX models.","abstract":"We compared 12 pediatric T cell acute lymphoblastic leukemias collected at initial diagnosis and relapse with their corresponding PDX models. The analysis was performed on genomic level (whole genome sequencing (WGS), whole exome sequencing (WES), multiplex ligation probe amplification (MLPA), targeted sequencing) and the epigenetic level (DNA methylation, Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq)). In sum, this study underlines the remarkable genomic stability, and for the first time documents the preservation of the epigenomic landscape in T-ALL-derived PDX models.","study_type":"Other","pubmed_ids":[30389682],"external_links":null,"is_released":true,"released_date":"2018-10-04T11:10:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003249","title":"Somatic_mutation_profiling_of_intestinal_crypts_from_IBD_Full_STDY","description":"Following on from our pilot study we will investigate  further the role that somatic mutations in intestinal stem cells play in IBD. We will use laser capture microdissection to ascertain epithelial cells from an individual crypts/vilus. We will extract DNA from these and use a new low-input material library prep methods to make accurate libraries for sequencing. We will perform 15X whole-genome sequencing of crypts biopsied from  patients. Biopsies have been taken from inflammed and noninflammed patches to compare mutation rates and mutational signatures. We will also test if crypts from inflammed patches of a single patient are clonal (either within a given inflammed patch or across inflammed patches). We will quantify the rate of cancer driver mutations in inflammed and non-inflammed crypts. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Following on from our pilot study we will investigate  further the role that somatic mutations in intestinal stem cells play in IBD. We will use laser capture microdissection to ascertain epithelial cells from an individual crypts/vilus. We will extract DNA from these and use a new low-input material library prep methods to make accurate libraries for sequencing. We will perform 15X whole-genome sequencing of crypts biopsied from  patients. Biopsies have been taken from inflammed and noninflammed patches to compare mutation rates and mutational signatures. We will also test if crypts from inflammed patches of a single patient are clonal (either within a given inflammed patch or across inflammed patches). We will quantify the rate of cancer driver mutations in inflammed and non-inflammed crypts.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-04T13:20:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003250","title":"1  Intratumoral  genetic  heterogeneity  and  clonal  evolution  following  neoadjuvant  chemoradiotherapy (nCRT)  in  locally  advanced  rectal  tumors.","description":"Purpose:  Neoadjuvant  chemoradiotherapy  (nCRT)  is  the  standard  treatment  forpatients  with  locally  advanced  rectal  cancer.  However,  little  is  known  about  the  effect  of  nCRT  in  the  mutational  landscape  and  intratumoral  genetic  heterogeneity  (ITGH)  of  rectal  tumors.  Moreover,  response  to  nCRT  vary  substantially  among  patients  and  the  genetic  determinants  of  treatment  response  are  not  fully  understood.  Here,  we  sought  to  determine  the  impact  of  nCRT  in  the  mutational  landscape  and  ITGH  of  rectal  tumors  and  to  identify  putative  drivers  of  therapeutic  resistance.  Patients  and  Methods:  We  analyzed  whole-exome  sequencing  (WES)  and  clinical  data  from  79  primary  non-treated  rectal  cancers  obtained  from  The  Cancer  Genome  Atlas  (TCGA).  We  also  compared  the  mutational  landscape  of  a  matched  set  of  peripheral  blood  cells,  irradiated  tumor-adjacent  colonic  mucosa  and  pre  and  post-treatment  tumor  samples  to  determine  the  iatrogenic  effects  of  nCRT  and  its  impact  in  tissue  genetic  heterogeneity.  Finally,  we  performed  WES  of  7  matched  pre  and  post-treatment  tumor  samples  to  examine  how  nCRT  affects  the  clonal  architecture  of  rectal  tumors.  Results:  We  show  that  rectal  tumors  exhibit  remarkable  ITGH,  which  increases  with  disease  progression.  We  also  show  that  nCRT,  per  se,  does  not  introduce  novel  somatic  mutations,  nor  alters  the  clonal  architecture  of  the  irradiated  colonic  mucosa.  Instead,  we  show  that  it  acts  as  a  potent  selective  pressure,  favoring  the  expansion  of  tumor  cell  subpopulations  more  prone  to  resist  therapy  and  increasing  ITGH  in  the  residual  tumor.  Conclusion:  Our  results  reveal  the  highly  heterogeneous  and  dynamic  clonal  architecture  of  rectal  tumors  undergoing  nCRT.  Our  results  also  uncover  putative  genetic  determinants  of  response  to  nCRT  and  a  possible  role  for  ITGH  in  predicting  treatment  outcome.","abstract":"Purpose:  Neoadjuvant  chemoradiotherapy  (nCRT)  is  the  standard  treatment  forpatients  with  locally  advanced  rectal  cancer.  However,  little  is  known  about  the  effect  of  nCRT  in  the  mutational  landscape  and  intratumoral  genetic  heterogeneity  (ITGH)  of  rectal  tumors.  Moreover,  response  to  nCRT  vary  substantially  among  patients  and  the  genetic  determinants  of  treatment  response  are  not  fully  understood.  Here,  we  sought  to  determine  the  impact  of  nCRT  in  the  mutational  landscape  and  ITGH  of  rectal  tumors  and  to  identify  putative  drivers  of  therapeutic  resistance.  Patients  and  Methods:  We  analyzed  whole-exome  sequencing  (WES)  and  clinical  data  from  79  primary  non-treated  rectal  cancers  obtained  from  The  Cancer  Genome  Atlas  (TCGA).  We  also  compared  the  mutational  landscape  of  a  matched  set  of  peripheral  blood  cells,  irradiated  tumor-adjacent  colonic  mucosa  and  pre  and  post-treatment  tumor  samples  to  determine  the  iatrogenic  effects  of  nCRT  and  its  impact  in  tissue  genetic  heterogeneity.  Finally,  we  performed  WES  of  7  matched  pre  and  post-treatment  tumor  samples  to  examine  how  nCRT  affects  the  clonal  architecture  of  rectal  tumors.  Results:  We  show  that  rectal  tumors  exhibit  remarkable  ITGH,  which  increases  with  disease  progression.  We  also  show  that  nCRT,  per  se,  does  not  introduce  novel  somatic  mutations,  nor  alters  the  clonal  architecture  of  the  irradiated  colonic  mucosa.  Instead,  we  show  that  it  acts  as  a  potent  selective  pressure,  favoring  the  expansion  of  tumor  cell  subpopulations  more  prone  to  resist  therapy  and  increasing  ITGH  in  the  residual  tumor.  Conclusion:  Our  results  reveal  the  highly  heterogeneous  and  dynamic  clonal  architecture  of  rectal  tumors  undergoing  nCRT.  Our  results  also  uncover  putative  genetic  determinants  of  response  to  nCRT  and  a  possible  role  for  ITGH  in  predicting  treatment  outcome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-04T20:58:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003251","title":"Infiltrative and drug-resistant slow-cycling cells support metabolic heterogeneity in glioblastoma","description":"Metabolic reprogramming has been described in rapidly growing tumors, which are thought to mostly contain fast-cycling cells (FCCs) that have impaired mitochondrial function and rely on aerobic glycolysis. Here, we characterize the metabolic landscape of glioblastoma (GBM) and explore metabolic specificities as targetable vulnerabilities. Our studies highlight the metabolic heterogeneity in GBM, in which FCCs harness aerobic glycolysis, and slow-cycling cells (SCCs) preferentially utilize mitochondrial oxidative phosphorylation for their functions. SCCs display enhanced invasion and chemoresistance, suggesting their important role in tumor recurrence. SCCs also demonstrate increased lipid contents that are specifically metabolized under glucose-deprived conditions. Increased fatty acid transport in SCCs is targetable by pharmacological inhibition or genomic deletion of FABP7, both of which sensitize SCCs to metabolic stress. Furthermore, FABP7 inhibition, whether alone or in combination with glycolysis inhibition, leads to overall increased survival. Our studies reveal the existence of GBM cell subpopulations with distinct metabolic requirements and suggest that FABP7 is central to lipid metabolism in SCCs and that targeting FABP7-related metabolic pathways is a viable therapeutic strategy.","abstract":"Metabolic reprogramming has been described in rapidly growing tumors, which are thought to mostly contain fast-cycling cells (FCCs) that have impaired mitochondrial function and rely on aerobic glycolysis. Here, we characterize the metabolic landscape of glioblastoma (GBM) and explore metabolic specificities as targetable vulnerabilities. Our studies highlight the metabolic heterogeneity in GBM, in which FCCs harness aerobic glycolysis, and slow-cycling cells (SCCs) preferentially utilize mitochondrial oxidative phosphorylation for their functions. SCCs display enhanced invasion and chemoresistance, suggesting their important role in tumor recurrence. SCCs also demonstrate increased lipid contents that are specifically metabolized under glucose-deprived conditions. Increased fatty acid transport in SCCs is targetable by pharmacological inhibition or genomic deletion of FABP7, both of which sensitize SCCs to metabolic stress. Furthermore, FABP7 inhibition, whether alone or in combination with glycolysis inhibition, leads to overall increased survival. Our studies reveal the existence of GBM cell subpopulations with distinct metabolic requirements and suggest that FABP7 is central to lipid metabolism in SCCs and that targeting FABP7-related metabolic pathways is a viable therapeutic strategy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-05T16:18:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003252","title":"A Study to Evaluate Denosumab in Young Patients With Primary Breast Cancer (D-Beyond)","description":"This is a prospective, single arm phase IIa trial in which patients with early breast cancer will receive pre-operatively two doses of denosumab 120mg subcutaneously one week apart (maximum 12 days) followed by surgery. Tumor, normal breast tissue and blood samples will be collected at baseline and at surgery. Post-operative treatment will be at the discretion of the investigator.Primary objective: to determine if a short course of RANKL inhibition with denosumab can induce a decrease in tumor proliferation rates as determined by Ki67 immunohistochemistry (IHC) in newly diagnosed, early stage breast cancer in pre-menopausal women.","abstract":"This is a prospective, single arm phase IIa trial in which patients with early breast cancer will receive pre-operatively two doses of denosumab 120mg subcutaneously one week apart (maximum 12 days) followed by surgery. Tumor, normal breast tissue and blood samples will be collected at baseline and at surgery. Post-operative treatment will be at the discretion of the investigator.Primary objective: to determine if a short course of RANKL inhibition with denosumab can induce a decrease in tumor proliferation rates as determined by Ki67 immunohistochemistry (IHC) in newly diagnosed, early stage breast cancer in pre-menopausal women.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-08T15:16:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003253","title":"Neuronal_uptake_of_tau_protein_CRISPR_screen___preliminary_sequencing","description":"The objective of this research is to use CRISPR loss-of-function screens in human stem cell-derived neurons to identify: genes regulating efficiency of tau uptake (monomeric and aggregated) by human neurons, and genes regulating handling of extracellular tau by human neurons, with a focus on exit from endosomes.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"It is not clear how Alzheimer’s disease (AD) spreads through the nervous system: current models propose that tau/MAPT is released in regulated manner from neurons in vivo and in vitro (Pooler et al., 2013; Yamada et al., 2014). Extracellular tau/MAPT is taken up by different cell types in vivo and in vitro (Clavaguera et al., 2009; Guo and Lee, 2011), and two transgenic mouse models have demonstrated transfer of human tau between neurons (de Calignon et al., 2012; Liu et al., 2012). Recent studies of human iPSC-derived neurons suggest that extracellular tau exists as N-terminal truncated forms (Bright et al., 2015), although both N-terminally truncated and full length tau have been reported in human CSF (Yamada et al., 2011; Meredith et al., 2013). We have found that human neurons efficiently take up monomeric and aggregated tau by different routes, and that tau can exit the endosome to become post-translationally modified in the cytoplasm (unpublished data). The combination of human stem cell systems with whole genome CRISPR screens enables an unbiased approach to identify genes and pathways that regulate these fundamental aspects of dementia pathogenesis, informing human genetic studies and highlighting druggable targets and pathways.\nThe objective of this research is to use CRISPR loss-of-function screens in human stem cell-derived neurons to identify: genes regulating efficiency of tau uptake (monomeric and aggregated) by human neurons, and genes regulating handling of extracellular tau by human neurons, with a focus on exit from endosomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003254","title":"46 CLL Whole Genome Sequencing Study","description":"Chronic lymphocytic leukaemia (CLL) consists of two biologically and clinically distinct subtypes defined by the abundance of somatic hypermutation (SHM) affecting the Ig variable heavy-chain locus (IgHV). The molecular mechanisms underlying these subtypes are incompletely understood. Here, we present a comprehensive whole-genome sequencing analysis of somatically acquired genetic events from 46 CLL patients, including a systematic comparison of coding and non-coding single nucleotide variants, copy number variants and structural variants, regions of kataegis and mutation signatures between IgHVmut and IgHVunmut subtypes.","abstract":"Chronic lymphocytic leukaemia (CLL) consists of two biologically and clinically distinct subtypes defined by the abundance of somatic hypermutation (SHM) affecting the Ig variable heavy-chain locus (IgHV). The molecular mechanisms underlying these subtypes are incompletely understood. Here, we present a comprehensive whole-genome sequencing analysis of somatically acquired genetic events from 46 CLL patients, including a systematic comparison of coding and non-coding single nucleotide variants, copy number variants and structural variants, regions of kataegis and mutation signatures between IgHVmut and IgHVunmut subtypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-09T08:19:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003255","title":"Detection of cell-free DNA fragmentation and copy number alterations in cerebrospinal fluid from glioma patients","description":"Glioma is difficult to detect or characterise using current liquid biopsy approaches.  Detection of cell-free tumor DNA (cftDNA) in cerebrospinal fluid (CSF) has been proposed as an alternative to detection in plasma. We used shallow whole-genome sequencing (sWGS, at a coverage of &lt; 0.4x) of cell-free DNA from the CSF of 13 patients with primary glioma to determine somatic copy number alterations and DNA fragmentation patterns. This allowed us to determine the presence of cftDNA in CSF without any prior knowledge of point mutations present in the tumor. We also showed that the fragmentation pattern of cell-free DNA in CSF is different from that in plasma. This low-cost screening method provides information on the tumor genome and can be used to target those patients with high levels of cftDNA for further larger-scale sequencing, such as by whole-exome and whole-genome sequencing.","abstract":"Glioma is difficult to detect or characterise using current liquid biopsy approaches.  Detection of cell-free tumor DNA (cftDNA) in cerebrospinal fluid (CSF) has been proposed as an alternative to detection in plasma. We used shallow whole-genome sequencing (sWGS, at a coverage of &lt; 0.4x) of cell-free DNA from the CSF of 13 patients with primary glioma to determine somatic copy number alterations and DNA fragmentation patterns. This allowed us to determine the presence of cftDNA in CSF without any prior knowledge of point mutations present in the tumor. We also showed that the fragmentation pattern of cell-free DNA in CSF is different from that in plasma. This low-cost screening method provides information on the tumor genome and can be used to target those patients with high levels of cftDNA for further larger-scale sequencing, such as by whole-exome and whole-genome sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-09T09:05:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003256","title":"Molecular Characterization of ETMRs","description":"ETMRs are poorly characterized embryonal brain tumors with a dismal outcome. We collected tumors from 184 ETMR patients and 23 matched recurrences to investigate the genomic landscape of this distinct entity. Tumors without C19MC amplification, the proposed driver, harbor other miRNA related aberrations like DICER1 mutations and amplifications of the MIR17-92 miRNA cluster. All tumors behave molecularly similar and no subgrouping was observed. Whole-genome sequencing revealed an overall low recurrence of SNVs, but highly prevalent R-loop associated genomic instability. Finally, we show that targeting R-loops with TOP1 and PARP inhibitors might be an effective treatment strategy for this deadly disease.","abstract":"ETMRs are poorly characterized embryonal brain tumors with a dismal outcome. We collected tumors from 184 ETMR patients and 23 matched recurrences to investigate the genomic landscape of this distinct entity. Tumors without C19MC amplification, the proposed driver, harbor other miRNA related aberrations like DICER1 mutations and amplifications of the MIR17-92 miRNA cluster. All tumors behave molecularly similar and no subgrouping was observed. Whole-genome sequencing revealed an overall low recurrence of SNVs, but highly prevalent R-loop associated genomic instability. Finally, we show that targeting R-loops with TOP1 and PARP inhibitors might be an effective treatment strategy for this deadly disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-09T14:28:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003257","title":"MYCN Amplification and ATRX Mutations are Incompatible in Neuroblastoma","description":"Age and stage of disease at diagnosis is associated with outcome in neuroblastoma. A previous study identified ATRX point mutations and in-frame deletions in older patients with stage 4 disease. To validate the frequency of ATRX mutations and assess the relation of mutations and known prognostic variables, we collaborated with the Children’s Oncology Group and sequenced the entire ATRX genomic locus in 475 neuroblastoma tumor samples to validate the frequency of ATRX mutations and assess the relation of mutations and known prognostic variables.  Older age at diagnosis, stage 4 disease, and unfavorable histology were significantly associated with mutations in the ATRX gene; MYCN amplification was mutually exclusive from ATRX mutations. To directly test if ATRX mutations and MYCN amplification are incompatible in neuroblastoma, we mutated the ATRX gene in MYCN amplified neuroblastoma cell lines and ectopically expressed MYCN in ATRX mutant neuroblastoma cell lines. Both approaches showed that ATRX and MYCN amplification are incompatible in neuroblastoma in culture and in vivo. To gain a better understanding of the underlying molecular and cellular mechanisms of this incompatibility, we performed a series of experiments including telomere analysis, epigenetic profiling, electron microscopic analysis and metabolic profiling. We discovered that induction of MYCN expression in ATRX mutant neuroblastomas cells leads to metabolic reprogramming, mitochondrial dysfunction, increased reactive oxygen species and replicative stress. We propose that this leads to synthetic lethality in ATRX mutant neuroblastomas because of the underlying replicative stress in those cells as a result of dysfunction of this essential histone chaperone.","abstract":"Age and stage of disease at diagnosis is associated with outcome in neuroblastoma. A previous study identified ATRX point mutations and in-frame deletions in older patients with stage 4 disease. To validate the frequency of ATRX mutations and assess the relation of mutations and known prognostic variables, we collaborated with the Children’s Oncology Group and sequenced the entire ATRX genomic locus in 475 neuroblastoma tumor samples to validate the frequency of ATRX mutations and assess the relation of mutations and known prognostic variables.  Older age at diagnosis, stage 4 disease, and unfavorable histology were significantly associated with mutations in the ATRX gene; MYCN amplification was mutually exclusive from ATRX mutations. To directly test if ATRX mutations and MYCN amplification are incompatible in neuroblastoma, we mutated the ATRX gene in MYCN amplified neuroblastoma cell lines and ectopically expressed MYCN in ATRX mutant neuroblastoma cell lines. Both approaches showed that ATRX and MYCN amplification are incompatible in neuroblastoma in culture and in vivo. To gain a better understanding of the underlying molecular and cellular mechanisms of this incompatibility, we performed a series of experiments including telomere analysis, epigenetic profiling, electron microscopic analysis and metabolic profiling. We discovered that induction of MYCN expression in ATRX mutant neuroblastomas cells leads to metabolic reprogramming, mitochondrial dysfunction, increased reactive oxygen species and replicative stress. We propose that this leads to synthetic lethality in ATRX mutant neuroblastomas because of the underlying replicative stress in those cells as a result of dysfunction of this essential histone chaperone.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-09T15:47:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003258","title":"Enhanced detection of circulating tumor DNA by fragment size analysis","description":"Existing methods to improve detection of circulating tumor DNA (ctDNA) have focused on sensitivity for detecting genomic alterations but have rarely considered the biological properties of plasma cell-free DNA (cfDNA). We hypothesized that differences in fragment lengths of circulating DNA could be exploited to enhance sensitivity for detecting the presence of ctDNA and for non-invasive genomic analysis of cancer. We surveyed ctDNA fragment sizes in 344 plasma samples from 200 cancer patients using low-pass whole-genome sequencing (0.4×). To establish the size distribution of mutant ctDNA, tumor-guided personalized deep sequencing was performed in 19 patients. We detected enrichment of ctDNA in fragment sizes between 90–150 bp, and developed methods for in vitro and in silico size selection of these fragments. Selecting fragments between 90–150 bp improved detection of tumor DNA, with more than 2-fold median enrichment in &amp;gt;95% of cases, and more than 4-fold enrichment in &amp;gt; 10% of cases. Analysis of size-selected cfDNA identified clinically actionable mutations and copy number alterations that were otherwise not detected. Identification of plasma samples from patients with advanced cancer was improved by predictive models integrating fragment length and copy number analysis of cfDNA, with AUC&amp;gt; 0.99 compared to AUC &amp;lt; 0.80 without fragmentation features. Increased identification of cfDNA from patients with glioma, renal, and pancreatic cancer was achieved with AUC &amp;gt; 0.91, compared to AUC &amp;lt; 0.5 without fragmentation features. Fragment size analysis and selective sequencing of specific fragment sizes can boost ctDNA detection. This could reduce the required depth of cfDNA sequencing for clinical applications, earlier diagnosis and study of tumor biology.","abstract":"Existing methods to improve detection of circulating tumor DNA (ctDNA) have focused on sensitivity for detecting genomic alterations but have rarely considered the biological properties of plasma cell-free DNA (cfDNA). We hypothesized that differences in fragment lengths of circulating DNA could be exploited to enhance sensitivity for detecting the presence of ctDNA and for non-invasive genomic analysis of cancer. We surveyed ctDNA fragment sizes in 344 plasma samples from 200 cancer patients using low-pass whole-genome sequencing (0.4×). To establish the size distribution of mutant ctDNA, tumor-guided personalized deep sequencing was performed in 19 patients. We detected enrichment of ctDNA in fragment sizes between 90–150 bp, and developed methods for in vitro and in silico size selection of these fragments. Selecting fragments between 90–150 bp improved detection of tumor DNA, with more than 2-fold median enrichment in &amp;gt;95% of cases, and more than 4-fold enrichment in &amp;gt; 10% of cases. Analysis of size-selected cfDNA identified clinically actionable mutations and copy number alterations that were otherwise not detected. Identification of plasma samples from patients with advanced cancer was improved by predictive models integrating fragment length and copy number analysis of cfDNA, with AUC&amp;gt; 0.99 compared to AUC &amp;lt; 0.80 without fragmentation features. Increased identification of cfDNA from patients with glioma, renal, and pancreatic cancer was achieved with AUC &amp;gt; 0.91, compared to AUC &amp;lt; 0.5 without fragmentation features. Fragment size analysis and selective sequencing of specific fragment sizes can boost ctDNA detection. This could reduce the required depth of cfDNA sequencing for clinical applications, earlier diagnosis and study of tumor biology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-09T16:53:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003259","title":"10X_Single_Cell_whole_genome_sequencing_of_the_human_heart_tissue","description":"The aim of this project is to profile human heart on a single-cell level. Cardiac human tissue will be sampled from both adult and fetal donors and will be processed for single cell and single nuclei RNA sequencing and spatialtranscriptomics. This whole genome sequencing will be used to de-multiplex the samples. This will provide us with a cellular composition of the heart and allow us to track its changes during development.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The aim of this project is to profile human heart on a single-cell level. Cardiac human tissue will be sampled from both adult and fetal donors and will be processed for single cell and single nuclei RNA sequencing and spatialtranscriptomics. This whole genome sequencing will be used to de-multiplex the samples. This will provide us with a cellular composition of the heart and allow us to track its changes during development.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003260","title":"Functional_Genomics_OA_2018_RNA","description":"OA affects &gt;40% of individuals over 70y and is a leading cause of pain and loss of physical function in the UK, affecting 8.5 million patients. The molecular changes leading to the pathogenesis of OA are still poorly understood We will obtain diseased and non-diseased tissue (cartilage) following total knee replacement surgery, coupled with a blood sample. This study follows on from previous successful work with UK-based orthopaedic surgeon collaborators. We will generate genotype data and will characterise the pairs of diseased and non-diseased tissue samples in terms of transcription (RNASeq). We will apply integrative approaches to combine information across the –omics levels to characterise genes, pathways, and networks that underlie osteoarthritis progression.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"OA affects &gt;40% of individuals over 70y and is a leading cause of pain and loss of physical function in the UK, affecting 8.5 million patients. The molecular changes leading to the pathogenesis of OA are still poorly understood The samples were obtained from diseased and non-diseased tissue (cartilage) following total knee replacement surgery, coupled with a blood sample. This study follows on from previous successful work with UK-based orthopaedic surgeon collaborators.  We have generated genotype data and characterised the pairs of diseased and non-diseased tissue samples in terms of transcription (RNASeq). We applied integrative approaches to combine information across the –omics levels to characterise genes, pathways, and networks that underlie osteoarthritis progression.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003261","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___GI___Chemotherapy___WES","description":"Somatic mutations (driver mutations) and clonal dynamics in normal human tissues from the gastrointestinal tract of individuals exposed to chemotherapy and other known genotoxins.","abstract":"The aim of this project is to investigate somatic mutations and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the study of normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to identify and isolate specific cell populations which are then subjected to whole exome sequencing to describe driver mutation frequency and clonal expansions in normal tissues.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003262","title":"Combination of Flow Cytometry and Functional Imaging for Monitoring of Residual Disease in Myeloma","description":"The iliac crest is the sampling site for minimal residual disease (MRD) monitoring in Multiple Myeloma (MM). However, the disease distribution is often heterogeneous, and imaging can be used to complement MRD detection at a single site. We have investigated patients in complete remission (CR) during first-line or salvage therapy, for whom MRD flow-cytometry and the two imaging modalities positron-emission-tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) were performed at the onset of CR. Residual focal lesions (FLs), detectable in 24% of first-line patients, were associated with short progression-free survival (PFS), with DW-MRI detecting disease in more patients. In some patients, FLs were only PET-positive, indicating that the two approaches are complementary. Combining MRD and imaging improved prediction of outcome, with double-negative and double-positive features defining groups with excellent and dismal PFS, respectively. FLs were a rare event (12%) in first-line MRD-negative CR patients. In contrast, patients achieving an MRD-negative CR during salvage therapy frequently had FLs (50%). Multi-region sequencing and imaging in an MRD-negative patient showed persistence of spatially separated clones. In conclusion, we show that DW-MRI is a promising tool for monitoring residual disease that complements PET and should be combined with MRD.","abstract":"The iliac crest is the sampling site for minimal residual disease (MRD) monitoring in Multiple Myeloma (MM). However, the disease distribution is often heterogeneous, and imaging can be used to complement MRD detection at a single site. We have investigated patients in complete remission (CR) during first-line or salvage therapy, for whom MRD flow-cytometry and the two imaging modalities positron-emission-tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) were performed at the onset of CR. Residual focal lesions (FLs), detectable in 24% of first-line patients, were associated with short progression-free survival (PFS), with DW-MRI detecting disease in more patients. In some patients, FLs were only PET-positive, indicating that the two approaches are complementary. Combining MRD and imaging improved prediction of outcome, with double-negative and double-positive features defining groups with excellent and dismal PFS, respectively. FLs were a rare event (12%) in first-line MRD-negative CR patients. In contrast, patients achieving an MRD-negative CR during salvage therapy frequently had FLs (50%). Multi-region sequencing and imaging in an MRD-negative patient showed persistence of spatially separated clones. In conclusion, we show that DW-MRI is a promising tool for monitoring residual disease that complements PET and should be combined with MRD.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003263","title":"Analysis of translatome, truncating mutations, lncRNA,  circRNA and microproteins of 80 human DCM cases and controls","description":"The regulation of gene expression in healthy and diseased human tissues is incompletely understood and has primarily been studied on the transcriptional level. Here, we quantify the impact of translation on gene expression and annotate novel translational events in 80 human hearts. These include 65 tissues from patients with dilated cardiomyopathy (DCM) - the most common cause of heart transplantation – and 15 unaffected controls. We show that translational regulation modulates disease-associated molecular processes. Further, we evaluate ribosome dynamics at protein truncating variants revealing incomplete termination of translation at titin-truncating variants (TTNtv) that commonly cause DCM. Finally, we identify dozens of unknown microproteins translated from lncRNAs and circRNAs and link these to mitochondrial processes. Several microproteins are expressed from lncRNAs with previously demonstrated function, suggesting a dual coding and noncoding role. This resource will stimulate novel functional investigations into cardiac biology in health and disease and may serve as a blueprint for characterizing the translational landscape of other human tissues.","abstract":"The regulation of gene expression in healthy and diseased human tissues is incompletely understood and has primarily been studied on the transcriptional level. Here, we quantify the impact of translation on gene expression and annotate novel translational events in 80 human hearts. These include 65 tissues from patients with dilated cardiomyopathy (DCM) - the most common cause of heart transplantation – and 15 unaffected controls. We show that translational regulation modulates disease-associated molecular processes. Further, we evaluate ribosome dynamics at protein truncating variants revealing incomplete termination of translation at titin-truncating variants (TTNtv) that commonly cause DCM. Finally, we identify dozens of unknown microproteins translated from lncRNAs and circRNAs and link these to mitochondrial processes. Several microproteins are expressed from lncRNAs with previously demonstrated function, suggesting a dual coding and noncoding role. This resource will stimulate novel functional investigations into cardiac biology in health and disease and may serve as a blueprint for characterizing the translational landscape of other human tissues.","study_type":"Other","pubmed_ids":[31155234],"external_links":null,"is_released":true,"released_date":"2018-10-15T14:49:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003264","title":"X10_sequencing_of_Oesophageal_Adenocarcinoma_Organoids","description":"X10 Sequencing of 5 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical resection of the tumour. All model derivations took place with the CGaP facility in Sanger.  This PacBio data will be combined with other sequencing data in order to generate accurate reference cancer genomes.","abstract":"There is complex interplay between underlying genetic sequence and epigenetic factors, however this interplay is still illusive. Massively reconstructed cancer genomes can be used in order to better understand this relationship. Six oesophageal adenocarcinoma organoids will be sequenced using long read sequencing technologies and will be profiled for a range of epigenetic marks. Combination of genetic and epigenetic data will allow the thorough characterisation of reference cancer genomes and will provide novel insights into mechanisms of gene regulation.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-16T14:34:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003265","title":"Identification of the molecular relationship between intravenous leiomyomatosis and uterine myoma using RNA sequencing","description":"The purpose of this study was to explore the potential relationship between intravenous leiomyomatosis (IVL) and uterine myoma (UM) at the molecular level.RNA-sequencing was performed on IVL tumours, UM tumours, and adjacent normal uterine muscle. We compared the gene expression levels between IVL and normal uterine muscle, and between UM and normal uterine muscle, to identify differentially expressed genes (DEGs). We then used Gene Ontology enrichment analysis to determine the functions of the DEGs and perform specimen cluster analysis.We obtained 98 DEGs between IVL and adjacent normal uterine muscle, and 61 DEGs between UM and adjacent normal uterine muscle. Functional enrichment of both IVL and UM DEGs showed their associations with hormone stimulus, extracellular matrix, and cell adhesion. Unsupervised clustering analysis showed that IVL and UM could not be separated completely. Among these dysregulated genes, we found that HOXA13 showed a distinct dysregulated status between IVL and UM. HOXA13 may therefore serve as a biomarker to distinguish IVL and UM. Our results show that IVL and UM may have similar dysregulated gene networks. They may be closely related, and HOXA13 may serve as a biomarker to distinguish between IVL and UM.","abstract":"The purpose of this study was to explore the potential relationship between intravenous leiomyomatosis (IVL) and uterine myoma (UM) at the molecular level.RNA-sequencing was performed on IVL tumours, UM tumours, and adjacent normal uterine muscle. We compared the gene expression levels between IVL and normal uterine muscle, and between UM and normal uterine muscle, to identify differentially expressed genes (DEGs). We then used Gene Ontology enrichment analysis to determine the functions of the DEGs and perform specimen cluster analysis.We obtained 98 DEGs between IVL and adjacent normal uterine muscle, and 61 DEGs between UM and adjacent normal uterine muscle. Functional enrichment of both IVL and UM DEGs showed their associations with hormone stimulus, extracellular matrix, and cell adhesion. Unsupervised clustering analysis showed that IVL and UM could not be separated completely. Among these dysregulated genes, we found that HOXA13 showed a distinct dysregulated status between IVL and UM. HOXA13 may therefore serve as a biomarker to distinguish IVL and UM. Our results show that IVL and UM may have similar dysregulated gene networks. They may be closely related, and HOXA13 may serve as a biomarker to distinguish between IVL and UM.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003266","title":"Mullighan - PAX5-driven Subtypes","description":"Using integrated genomic analysis of 1.988 childhood and adult cases, we describe a revised taxonomy of B-cell acute lymphoblastic leukemia, which incorporates 23 subtypes defined by chromosomal rearrangements, sequence mutations, or heterogeneous genomic alterations. Two subtypes have frequent alterations of the B lymphoid transcription factor gene PAX5. One, PAX5alt, has diverse PAX5 alterations, and a second subtype is defined by a single mutation, PAX5 P80R. We show that P80R impairs B lymphoid development and promotes the development of B-ALL in vivo. These results demonstrate the utility of transcriptome sequencing to classify B-ALL and reinforce the central role of PAX5 as a checkpoint in B lymphoid maturation and leukemogenesis.","abstract":"Using integrated genomic analysis of 1.988 childhood and adult cases, we describe a revised taxonomy of B-cell acute lymphoblastic leukemia, which incorporates 23 subtypes defined by chromosomal rearrangements, sequence mutations, or heterogeneous genomic alterations. Two subtypes have frequent alterations of the B lymphoid transcription factor gene PAX5. One, PAX5alt, has diverse PAX5 alterations, and a second subtype is defined by a single mutation, PAX5 P80R. We show that P80R impairs B lymphoid development and promotes the development of B-ALL in vivo. These results demonstrate the utility of transcriptome sequencing to classify B-ALL and reinforce the central role of PAX5 as a checkpoint in B lymphoid maturation and leukemogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-16T19:54:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003267","title":"Exome Sequencing from PDX published in Castroviejo et al EMM 2018","description":null,"abstract":"Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are effective in cancers with defective homologous recombination DNA repair (HRR), including BRCA1/2-related cancers. A test to identify additional HRR-deficient tumors will help to extend their use in new indications. We evaluated the activity of the PARPi olaparib in patient-derived tumor xenografts (PDXs) from breast cancer (BC) patients and investigated mechanisms of sensitivity through exome sequencing, BRCA1 promoter methylation analysis and immunostaining of HRR proteins, including RAD51 nuclear foci. In an independent BC PDX panel, the predictive capacity of the RAD51 score and the homologous recombination deficiency (HRD) score were compared. To examine the clinical feasibility of the RAD51 assay we scored archival breast tumor samples, including PALB2-related hereditary cancers. The RAD51 score was highly discriminative of PARPi-sensitivity versus PARPi-resistance in BC PDXs and outperformed the genomic test. In clinical samples, all PALB2-related tumors were classified as HRR-deficient by the RAD51 score.\nThe functional biomarker RAD51 enables the identification of PARPi-sensitive BC and broadens the population who may benefit from this therapy beyond BRCA1/2-related cancers.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003268","title":"Severe acne GWAS and meta-analysis","description":null,"abstract":"Acne vulgaris is a highly heritable common, chronic inflammatory disease of the skin. We performed a genome-wide association study of 3,823 cases and 16,144 controls followed by meta-analysis with summary statistics from a previous study, with a total sample size of 26,722. We identified 20 independent association signals at 15 risk loci, 12 of which have not been previously implicated in the disease.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003269","title":"Mitochondrial DNA (mtDNA) analyses in patients with schizophrenia and healthy control individuals","description":null,"abstract":"1) To identify putative pathogenic mtDNA variants in patients with schizophrenia.\n2) To identify variants present in patients with schizophrenia that are absent in the healthy control group.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003270","title":"Mitochondrial DNA analyses in schizophrenia and healthy control individuals","description":null,"abstract":"1)\tTo identify putative pathogenic variants in the mitochondrial DNA of patients with schizophrenia.\n2)\tTo compare mitochondrial DNA sequences between patients with schizophrenia and healthy controls.\n3)\tTo associate mitochondrial DNA variants with blood lactate concentration.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003271","title":"Aged_bone_marrow_CHIP_screen_and_colony_clonal_dynamics","description":"We aim to screen these samples for somatic mutations associated with clonal haematopoiesis of indeterminate potential (CHIP) in order to identify samples to take forward for further work.","abstract":"Background to my wider project\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through this CHIP screen\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003272","title":"Mitochondrial DNA analyses in schizophrenia and healthy control individuals","description":null,"abstract":"1)\tTo identify putative pathogenic variants in the mitochondrial DNA of patients with schizophrenia.\n2)\tTo compare mitochondrial DNA sequences between patients with schizophrenia and healthy controls.\n3)\tTo associate mitochondrial DNA variants with blood lactate concentration.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003273","title":"Unravelling_sepsis_heterogeneity_through_trascriptomics__BioAID_","description":"There is marked heterogeneity in the septic response, which has hindered efforts to understand pathophysiology and develop targeted therapies. Molecular approaches may provide insights into variation in the host response, enabling biomarker development. Recent evidence suggests that transcriptomic sepsis response signatures (SRSs) can define patient subgroups associated with early outcome in sepsis. In this context, using transcriptomic approaches, the co-applicants were the first to identify differential gene signatures, or immune endotypes, correlating with outcome in sepsis, (Davenport E. et al, The Lancet Respiratory medicine, 2016); potentially providing a path to personalised treatment in sepsis. Specifically, this work defined two groups based on transcriptomic profiles: SRS group 1 being more associated with endotoxin tolerance demonstrating an immunosuppressed signature and is associated with higher mortality, whereas, SRS2 is more immune-heightened. However, despite the importance of these findings, previous studies have been underpowered, and limited in depth of data, to resolve these endophenotypes further. In this context, the Bioresource for Adult Infectious Disease (BioAID) offers substantial opportunities in terms of power, depth and breadth of data linked to biological samples of patients presenting acutely with the sepsis syndrome across the UK.  BioAID currently holds samples for DNA, RNA, serum and microbial isolates for more than 4,000 individuals (with a planned recruit of 10,000 individuals) and therefore provides a powerful resource for examining the underlying biology and correlates of sepsis syndrome with a view to informing early risk stratification of patients, need for critical care, and treatments.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"There is marked heterogeneity in the septic response, which has hindered efforts to understand pathophysiology and develop targeted therapies. Molecular approaches may provide insights into variation in the host response, enabling biomarker development. Recent evidence suggests that transcriptomic sepsis response signatures (SRSs) can define patient subgroups associated with early outcome in sepsis. In this context, using transcriptomic approaches, the co-applicants were the first to identify differential gene signatures, or immune endotypes, correlating with outcome in sepsis, (Davenport E. et al, The Lancet Respiratory medicine, 2016); potentially providing a path to personalised treatment in sepsis. Specifically, this work defined two groups based on transcriptomic profiles: SRS group 1 being more associated with endotoxin tolerance demonstrating an immunosuppressed signature and is associated with higher mortality, whereas, SRS2 is more immune-heightened. However, despite the importance of these findings, previous studies have been underpowered, and limited in depth of data, to resolve these endophenotypes further. In this context, the Bioresource for Adult Infectious Disease (BioAID) offers substantial opportunities in terms of power, depth and breadth of data linked to biological samples of patients presenting acutely with the sepsis syndrome across the UK.  BioAID currently holds samples for DNA, RNA, serum and microbial isolates for more than 4,000 individuals (with a planned recruit of 10,000 individuals) and therefore provides a powerful resource for examining the underlying biology and correlates of sepsis syndrome with a view to informing early risk stratification of patients, need for critical care, and treatments.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003274","title":"Genetic characterization of B-cell prolymphocytic leukemia: a hierarchical prognostic model involving MYC and TP53 abnormalities - RNA-seq","description":"B-cell prolymphocytic leukemia (B-PLL) is a rare disease, whose molecular pathology is largely unknown. We report here the cytogenetic and molecular findings in a large series of 34 B-PLL. Karyotype (K) was complex (≥3 abnormalities) in 73%, and highly complex (HCK≥5) in 45%. The most frequent chromosomal aberrations were: translocation targeting the MYC gene [t(MYC)] (62%), 17p deletion including TP53 gene (38%), trisomy 18/18q (30%), 13q14 deletion (29%), trisomy 3 (24%), trisomy 12 (24%) and 8p deletion (23%). Whole-Exome Sequencing performed in 16 patients revealed recurrent mutations in TP53 (6/16, 38%), MYD88 (n=4), BCOR (n=4), MYC (n=3), SF3B1 (n=3), FAT1 (n=3), SETD2 (n=2), CHD2 (n=2), CXCR4 (n=2) and BCLAF1 (n=2). The main group of patients (21/34, 62%) had a t(MYC) associated with a higher percentage of prolymphocytes (p=0.03), CD38 expression (p&lt;0.001), lower K complexity (p=0.0004), mutations in MYC and in genes involved in RNA metabolism and chromatin remodeling. Principal component analysis of gene expression data showed that patients with t(MYC) clustered together. A second group with MYC gain (5/34, 15%), was associated with HCK≥5 (p=0,01) and trisomy 3 (p=0,008). Altogether, 26/34 patients (76%) had a MYC activation, translocation or gain, that were mutually exclusive. We identified 3 distinct cytogenetic prognostic groups (p=0.0006): lower risk: absence of MYC activation (median not reached); intermediate risk: MYC activation without del17p (125 months); high risk: MYC activation + del17p (11 months). Our results show that cytogenetic analysis is a useful diagnostic tool in B-PLL that improves prognostic stratification.","abstract":"B-cell prolymphocytic leukemia (B-PLL) is a rare disease, whose molecular pathology is largely unknown. We report here the cytogenetic and molecular findings in a large series of 34 B-PLL. Karyotype (K) was complex (≥3 abnormalities) in 73%, and highly complex (HCK≥5) in 45%. The most frequent chromosomal aberrations were: translocation targeting the MYC gene [t(MYC)] (62%), 17p deletion including TP53 gene (38%), trisomy 18/18q (30%), 13q14 deletion (29%), trisomy 3 (24%), trisomy 12 (24%) and 8p deletion (23%). Whole-Exome Sequencing performed in 16 patients revealed recurrent mutations in TP53 (6/16, 38%), MYD88 (n=4), BCOR (n=4), MYC (n=3), SF3B1 (n=3), FAT1 (n=3), SETD2 (n=2), CHD2 (n=2), CXCR4 (n=2) and BCLAF1 (n=2). The main group of patients (21/34, 62%) had a t(MYC) associated with a higher percentage of prolymphocytes (p=0.03), CD38 expression (p&lt;0.001), lower K complexity (p=0.0004), mutations in MYC and in genes involved in RNA metabolism and chromatin remodeling. Principal component analysis of gene expression data showed that patients with t(MYC) clustered together. A second group with MYC gain (5/34, 15%), was associated with HCK≥5 (p=0,01) and trisomy 3 (p=0,008). Altogether, 26/34 patients (76%) had a MYC activation, translocation or gain, that were mutually exclusive. We identified 3 distinct cytogenetic prognostic groups (p=0.0006): lower risk: absence of MYC activation (median not reached); intermediate risk: MYC activation without del17p (125 months); high risk: MYC activation + del17p (11 months). Our results show that cytogenetic analysis is a useful diagnostic tool in B-PLL that improves prognostic stratification.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-18T14:48:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003275","title":"Genetic characterization of B-cell prolymphocytic leukemia: a hierarchical prognostic model involving MYC and TP53 abnormalities - WXS","description":"B-PLL is a rare disease, whose molecular pathology is largely unknown. We report here the cytogenetic and molecular findings in a large series of 34 B-PLL. Karyotype (K) was complex (≥3 abnormalities) in 73%, and highly complex (HCK≥5) in 45%. The most frequent chromosomal aberrations were: translocation targeting the MYC gene [t(MYC)] (62%), 17p deletion including TP53 gene (38%), trisomy 18/18q (30%), 13q14 deletion (29%), trisomy 3 (24%), trisomy 12 (24%) and 8p deletion (23%). Whole-Exome Sequencing performed in 16 patients revealed recurrent mutations in TP53 (6/16, 38%), MYD88 (n=4), BCOR (n=4), MYC (n=3), SF3B1 (n=3), FAT1 (n=3), SETD2 (n=2), CHD2 (n=2), CXCR4 (n=2) and BCLAF1 (n=2). The main group of patients (21/34, 62%) had a t(MYC) associated with a higher percentage of prolymphocytes (p=0.03), CD38 expression (p&lt;0.001), lower K complexity (p=0.0004), mutations in MYC and in genes involved in RNA metabolism and chromatin remodeling. Principal component analysis of gene expression data showed that patients with t(MYC) clustered together. A second group with MYC gain (5/34, 15%), was associated with HCK≥5 (p=0,01) and trisomy 3 (p=0,008). Altogether, 26/34 patients (76%) had a MYC activation, translocation or gain, that were mutually exclusive. We identified 3 distinct cytogenetic prognostic groups (p=0.0006): lower risk: absence of MYC activation (median not reached); intermediate risk: MYC activation without del17p (125 months); high risk: MYC activation + del17p (11 months). Our results show that cytogenetic analysis is a useful diagnostic tool in B-PLL that improves prognostic stratification.","abstract":"B-PLL is a rare disease, whose molecular pathology is largely unknown. We report here the cytogenetic and molecular findings in a large series of 34 B-PLL. Karyotype (K) was complex (≥3 abnormalities) in 73%, and highly complex (HCK≥5) in 45%. The most frequent chromosomal aberrations were: translocation targeting the MYC gene [t(MYC)] (62%), 17p deletion including TP53 gene (38%), trisomy 18/18q (30%), 13q14 deletion (29%), trisomy 3 (24%), trisomy 12 (24%) and 8p deletion (23%). Whole-Exome Sequencing performed in 16 patients revealed recurrent mutations in TP53 (6/16, 38%), MYD88 (n=4), BCOR (n=4), MYC (n=3), SF3B1 (n=3), FAT1 (n=3), SETD2 (n=2), CHD2 (n=2), CXCR4 (n=2) and BCLAF1 (n=2). The main group of patients (21/34, 62%) had a t(MYC) associated with a higher percentage of prolymphocytes (p=0.03), CD38 expression (p&lt;0.001), lower K complexity (p=0.0004), mutations in MYC and in genes involved in RNA metabolism and chromatin remodeling. Principal component analysis of gene expression data showed that patients with t(MYC) clustered together. A second group with MYC gain (5/34, 15%), was associated with HCK≥5 (p=0,01) and trisomy 3 (p=0,008). Altogether, 26/34 patients (76%) had a MYC activation, translocation or gain, that were mutually exclusive. We identified 3 distinct cytogenetic prognostic groups (p=0.0006): lower risk: absence of MYC activation (median not reached); intermediate risk: MYC activation without del17p (125 months); high risk: MYC activation + del17p (11 months). Our results show that cytogenetic analysis is a useful diagnostic tool in B-PLL that improves prognostic stratification.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-18T14:48:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003276","title":"Butyrate producers as potential next-generation probiotics: safety assessment of the administration of Butyricicoccus pullicaecorum to healthy volunteers","description":"Advances in gut microbiota research have triggered interest in developing colon butyrate producers as niche-specific next-generation probiotics, targeted at increasing colon butyrate production and countering disease-associated microbiota alterations. Crucial steps in the development of next-generation probiotics are the design of formulations with a reasonable shelf life as well as the safety demonstration of an intervention in healthy volunteers. One such potential next-generation butyrate-producing probiotic is Butyricicoccus pullicaecorum 25-3T, with demonstrated safety in in vitro as well as in animal models. Here, we examined the strain's safety, tolerability, and impact on microbiota composition and metabolic activity in healthy volunteers in a randomized, double blind, placebo-controlled, crossover study in 30 healthy volunteers. Study design consisted of two four-week intervention periods (108 CFU B. pullicaecorum [treatment] or maltodextrin [placebo] per day) with a three-week washout in between. We assessed adverse events, blood parameters (primary endpoints), and fecal microbiota composition and metabolite profiles (secondary endpoints).The number of reported adverse events during the B. pullicaecorum treatment was similar to placebo intervention, as were observed changes in blood chemistry parameters, bowel habits, and fecal calprotectin concentrations. Administration of the strain did not induce any disruptive effect in microbiota composition or metabolic activity. In this first human intervention trial with a butyrate-producing Clostridium cluster IV isolate, we demonstrated B. pullicaecorum 25-3T administration to be both safe and well tolerated by healthy participants. This safety study paves the way for the further development of the strain as a next-generation probiotic.","abstract":"Advances in gut microbiota research have triggered interest in developing colon butyrate producers as niche-specific next-generation probiotics, targeted at increasing colon butyrate production and countering disease-associated microbiota alterations. Crucial steps in the development of next-generation probiotics are the design of formulations with a reasonable shelf life as well as the safety demonstration of an intervention in healthy volunteers. One such potential next-generation butyrate-producing probiotic is Butyricicoccus pullicaecorum 25-3T, with demonstrated safety in in vitro as well as in animal models. Here, we examined the strain's safety, tolerability, and impact on microbiota composition and metabolic activity in healthy volunteers in a randomized, double blind, placebo-controlled, crossover study in 30 healthy volunteers. Study design consisted of two four-week intervention periods (108 CFU B. pullicaecorum [treatment] or maltodextrin [placebo] per day) with a three-week washout in between. We assessed adverse events, blood parameters (primary endpoints), and fecal microbiota composition and metabolite profiles (secondary endpoints).The number of reported adverse events during the B. pullicaecorum treatment was similar to placebo intervention, as were observed changes in blood chemistry parameters, bowel habits, and fecal calprotectin concentrations. Administration of the strain did not induce any disruptive effect in microbiota composition or metabolic activity. In this first human intervention trial with a butyrate-producing Clostridium cluster IV isolate, we demonstrated B. pullicaecorum 25-3T administration to be both safe and well tolerated by healthy participants. This safety study paves the way for the further development of the strain as a next-generation probiotic.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-18T15:45:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003277","title":"Atac sequencing study","description":null,"abstract":"Multiple myeloma (MM) is a cancerous pathology resulting from the clonal expansion of plasma cells, and characterized by abnormal production and secretion of antibody proteins. This disease shows a great heterogeneity, caused by both genetic and epigenetic abnormalities, and despite the numerous therapeutic advances remains an incurable pathology. Here we show that the RNA Polymerase II binding protein, Che-1/AATF is required for MM cells  growth  by  sustaining  genome  wide  transcription and  the recruitment  of  Pol  II  to  the  DNA.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003278","title":"A GWAS meta-analysis on severe acne on a European population of 26,722 individuals","description":"Acne vulgaris is a highly heritable common, chronic inflammatory disease of the skin. We performed a genome-wide association study of 3,823 cases and 16,144 controls followed by meta-analysis with summary statistics from a previous study, with a total sample size of 26,722. We identified 20 independent association signals at 15 risk loci, 12 of which have not been previously implicated in the disease.","abstract":"Acne vulgaris is a highly heritable common, chronic inflammatory disease of the skin. We performed a genome-wide association study of 3,823 cases and 16,144 controls followed by meta-analysis with summary statistics from a previous study, with a total sample size of 26,722. We identified 20 independent association signals at 15 risk loci, 12 of which have not been previously implicated in the disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-22T21:45:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003279","title":"Unravelling_sepsis_heterogeneity_through_trascriptomics__BioAID_UCL_","description":"There is marked heterogeneity in the septic response, which has hindered efforts to understand pathophysiology and develop targeted therapies. Molecular approaches may provide insights into variation in the host response, enabling biomarker development. Recent evidence suggests that transcriptomic sepsis response signatures (SRSs) can define patient subgroups associated with early outcome in sepsis. In this context, using transcriptomic approaches, the co-applicants were the first to identify differential gene signatures, or immune endotypes, correlating with outcome in sepsis, (Davenport E. et al, The Lancet Respiratory medicine, 2016); potentially providing a path to personalised treatment in sepsis. Specifically, this work defined two groups based on transcriptomic profiles: SRS group 1 being more associated with endotoxin tolerance demonstrating an immunosuppressed signature and is associated with higher mortality, whereas, SRS2 is more immune-heightened. However, despite the importance of these findings, previous studies have been underpowered, and limited in depth of data, to resolve these endophenotypes further. In this context, the Bioresource for Adult Infectious Disease (BioAID) offers substantial opportunities in terms of power, depth and breadth of data linked to biological samples of patients presenting acutely with the sepsis syndrome across the UK.  BioAID currently holds samples for DNA, RNA, serum and microbial isolates for more than 4,000 individuals (with a planned recruit of 10,000 individuals) and therefore provides a powerful resource for examining the underlying biology and correlates of sepsis syndrome with a view to informing early risk stratification of patients, need for critical care, and treatments.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"There is marked heterogeneity in the septic response, which has hindered efforts to understand pathophysiology and develop targeted therapies. Molecular approaches may provide insights into variation in the host response, enabling biomarker development. Recent evidence suggests that transcriptomic sepsis response signatures (SRSs) can define patient subgroups associated with early outcome in sepsis. In this context, using transcriptomic approaches, the co-applicants were the first to identify differential gene signatures, or immune endotypes, correlating with outcome in sepsis, (Davenport E. et al, The Lancet Respiratory medicine, 2016); potentially providing a path to personalised treatment in sepsis. Specifically, this work defined two groups based on transcriptomic profiles: SRS group 1 being more associated with endotoxin tolerance demonstrating an immunosuppressed signature and is associated with higher mortality, whereas, SRS2 is more immune-heightened. However, despite the importance of these findings, previous studies have been underpowered, and limited in depth of data, to resolve these endophenotypes further. In this context, the Bioresource for Adult Infectious Disease (BioAID) offers substantial opportunities in terms of power, depth and breadth of data linked to biological samples of patients presenting acutely with the sepsis syndrome across the UK.  BioAID currently holds samples for DNA, RNA, serum and microbial isolates for more than 4,000 individuals (with a planned recruit of 10,000 individuals) and therefore provides a powerful resource for examining the underlying biology and correlates of sepsis syndrome with a view to informing early risk stratification of patients, need for critical care, and treatments.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003280","title":"INSPIRE - Investigator-initiated Phase 2 Study of Pembrolizumab Immunological Response in Metastatic Solid Tumors","description":"Whole exome and RNA sequencing source data for:\r\n\r\nClouthier, D.L., Lien, S.C., Yang, S.Y.C. et al. An interim report on the investigator-initiated phase 2 study of pembrolizumab immunological response evaluation (INSPIRE). j. immunotherapy cancer 7, 72 (2019). https://doi.org/10.1186/s40425-019-0541-0\r\n\r\nBratman S*, Yang SYC*, Iafolla MAJ, Liu Z, Hansen AR, Bedard P, Lheureux S, Spreafico A, Razak AA, Shchegrova S, Louie M, Billings P, Zimmerman B, Sethi H, Aleshi A, Torti D, Marsh K, Eagles J, Cirlan I, Hanna Y, Clouthier D, Lien SC, Ohashi PS, Xu W, Siu LL, Pugh TJ. Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Nature Cancer. 2020:1:873-881. https://doi.org/10.1038/s43018- 020-0096-5.\r\n\r\nYang SYC, Lien SC, Wang BX, Clouthier DL, Hanna Y, Cirlan I, Zhu K, Bruce JP, El Ghamrasni S, Iafallo MAJ, Oliva M, Hansen AR, Spreafico A, Bedard PL, Lheureux S, Razak A, Speers V, Berman HK, Aleshin A, Haibe-Kains B, Brooks DG, McGaha TL, Butler MO, Bratman SV, Ohashi PS, Siu LL, and Pugh TJ. Pan-cancer analysis of longitudinal metastatic tumors reveals genomic alterations and immune landscape dynamics associated with pembrolizumab sensitivity. Nature Comm 2021:12, 5137. https://doi.org/10.1038/s41467-021-25432-7","abstract":"Whole exome and RNA sequencing source data for:\n\nClouthier, D.L., Lien, S.C., Yang, S.Y.C. et al. An interim report on the investigator-initiated phase 2 study of pembrolizumab immunological response evaluation (INSPIRE). j. immunotherapy cancer 7, 72 (2019). https://doi.org/10.1186/s40425-019-0541-0\n\nBratman S*, Yang SYC*, Iafolla MAJ, Liu Z, Hansen AR, Bedard P, Lheureux S, Spreafico A, Razak AA, Shchegrova S, Louie M, Billings P, Zimmerman B, Sethi H, Aleshi A, Torti D, Marsh K, Eagles J, Cirlan I, Hanna Y, Clouthier D, Lien SC, Ohashi PS, Xu W, Siu LL, Pugh TJ. Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Nature Cancer. 2020:1:873-881. https://doi.org/10.1038/s43018- 020-0096-5.\n\nYang SYC, Lien SC, Wang BX, Clouthier DL, Hanna Y, Cirlan I, Zhu K, Bruce JP, El Ghamrasni S, Iafallo MAJ, Oliva M, Hansen AR, Spreafico A, Bedard PL, Lheureux S, Razak A, Speers V, Berman HK, Aleshin A, Haibe-Kains B, Brooks DG, McGaha TL, Butler MO, Bratman SV, Ohashi PS, Siu LL, and Pugh TJ. Pan-cancer analysis of longitudinal metastatic tumors reveals genomic alterations and immune landscape dynamics associated with pembrolizumab sensitivity. Nature Comm 2021:12, 5137. https://doi.org/10.1038/s41467-021-25432-7","study_type":"Cancer Genomics","pubmed_ids":[35121950],"external_links":null,"is_released":true,"released_date":"2018-10-25T15:52:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003281","title":"Mutations of whole genome sequencing in single cells in normal esophageal epithelium","description":"In order to obtain insight into the mutations in normal esophageal epithelium, we performed whole genome sequencing of 13 single cell-derived colonies isolated from 7 cases.","abstract":"In order to obtain insight into the mutations in normal esophageal epithelium, we performed whole genome sequencing of 13 single cell-derived colonies isolated from 7 cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-29T05:38:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003282","title":"Paired whole exome sequence of subcutaneous panniculitis-like T-cell lymphoma.","description":"Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of peripheral T-cell lymphoma affecting younger cases and associated with hemophagocytic lymphohistiocytosis.  To clarify molecular pathogenesis of SPTCL, we analyzed paired tumor and germline DNAs from 13 patients by whole exome sequencing.","abstract":"Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of peripheral T-cell lymphoma affecting younger cases and associated with hemophagocytic lymphohistiocytosis.  To clarify molecular pathogenesis of SPTCL, we analyzed paired tumor and germline DNAs from 13 patients by whole exome sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-29T06:38:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003283","title":"Genome_wide_association_study_of_vaccine_response_in_infants_from_subSaharan_Africa","description":"In sub-Saharan Africa, many vaccines have been shown to have reduced efficacy relative to\nEurope and North America. Both environmental and genetic factors are known to be\nresponsible for this variation, including adaptive evolutionary changes in the human and\npathogen genome. Previous findings suggest that there may several genes residing outside\nof the HLA locus that may influence genetic susceptibility to infection, response to treatment s\nand vaccine efficacy. We therefore propose a GWAS to identify variants associated with a\ndifferential response to some of the most commonly used vaccines. This study will be unique\nin analysing multiple vaccines simultaneously, which could provide not only the opportunity to\ndetect new genetic determinants of vaccine response and replicate biological candidate\ngenes, but also provide insights into whether the molecular mechanisms responsible for\nvaccine efficacy differ among different disease vaccines and subtypes. The identification of\nnovel genes and pathways associated with variable vaccine response should help us to\ndevelop more immunogenic and effective vaccines both against those diseases for which\nvaccines already exist, and also against other major infections.\nWe aim to genotype 1,500 children from the Entebbe Mother and Baby (EMaB) study, an ongoing\nbirth cohort in southern Uganda, using the Illumina HumanOmni 2.5M chip array.\nMeasures of serological response at one year to seven vaccinations received in infancy\n(diphtheria, tetanus, pertussis, Haemophilus influenzae, hepatitis B, measles and polio) will\nbe analysed as quantitative traits using mixed model analyses and a combined 1000G and\nAfrican Genome Variation Project reference panel. DNA has been extracted and is ready to\nbe shipped to WTSI.\nAdditional phenotypes within the cohort include, response to BCG immunisation, data on\nmalaria episodes and immunological markers of infection (antibodies for malarial infection)\nand information on clinical presentation and markers of atopy and eczema. Several cytokine\nmeasures are also available in the EMaB cohort, which would complement our GWAS of\ncardiometabolic and infectious traits in the General Population Cohort Study (on-going\nanalyses, including antibody titres for hepatitis B). We also have access to equivalent cohorts\nin South Africa (Madhi) with vaccination response phenotypes on up to 2,000 children, as well\nas response to pneumonococcal and meningococcal vaccination with appropriate consents\nfor genomic research. These cohorts will form our replication studies for the vaccination\nresponse phenotypes in the EMaB Study.","abstract":"In sub-Saharan Africa, many vaccines have been shown to have reduced efficacy relative to\nEurope and North America. Both environmental and genetic factors are known to be\nresponsible for this variation, including adaptive evolutionary changes in the human and\npathogen genome. Previous findings suggest that there may several genes residing outside\nof the HLA locus that may influence genetic susceptibility to infection, response to treatment s\nand vaccine efficacy. We therefore propose a GWAS to identify variants associated with a\ndifferential response to some of the most commonly used vaccines. This study will be unique\nin analysing multiple vaccines simultaneously, which could provide not only the opportunity to\ndetect new genetic determinants of vaccine response and replicate biological candidate\ngenes, but also provide insights into whether the molecular mechanisms responsible for\nvaccine efficacy differ among different disease vaccines and subtypes. The identification of\nnovel genes and pathways associated with variable vaccine response should help us to\ndevelop more immunogenic and effective vaccines both against those diseases for which\nvaccines already exist, and also against other major infections.\nWe aim to genotype 1,500 children from the Entebbe Mother and Baby (EMaB) study, an ongoing\nbirth cohort in southern Uganda, using the Illumina HumanOmni 2.5M chip array.\nMeasures of serological response at one year to seven vaccinations received in infancy\n(diphtheria, tetanus, pertussis, Haemophilus influenzae, hepatitis B, measles and polio) will\nbe analysed as quantitative traits using mixed model analyses and a combined 1000G and\nAfrican Genome Variation Project reference panel. DNA has been extracted and is ready to\nbe shipped to WTSI.\nAdditional phenotypes within the cohort include, response to BCG immunisation, data on\nmalaria episodes and immunological markers of infection (antibodies for malarial infection)\nand information on clinical presentation and markers of atopy and eczema. Several cytokine\nmeasures are also available in the EMaB cohort, which would complement our GWAS of\ncardiometabolic and infectious traits in the General Population Cohort Study (on-going\nanalyses, including antibody titres for hepatitis B). We also have access to equivalent cohorts\nin South Africa (Madhi) with vaccination response phenotypes on up to 2,000 children, as well\nas response to pneumonococcal and meningococcal vaccination with appropriate consents\nfor genomic research. These cohorts will form our replication studies for the vaccination\nresponse phenotypes in the EMaB Study.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003284","title":"Molecular profiling of longitudinally observed small colorectal polyps: a cohort study","description":"Knowledge of the natural history of colorectal adenomas is limited because these lesions are removed upon detection. The few studies in which small adenomas have been left in situ for a limited period of time have shown that most lesions remain stable or even completely vanish. Lesions that have grown in size more often turn out to be advanced adenomas when resected. Specific DNA copy number changes (cancer associated events or CAEs) are associated with progression of adenomas to cancer. The aim of the study was to evaluate whether growth of small colorectal polyps left in situ is associated with specific molecular features.","abstract":"Knowledge of the natural history of colorectal adenomas is limited because these lesions are removed upon detection. The few studies in which small adenomas have been left in situ for a limited period of time have shown that most lesions remain stable or even completely vanish. Lesions that have grown in size more often turn out to be advanced adenomas when resected. Specific DNA copy number changes (cancer associated events or CAEs) are associated with progression of adenomas to cancer. The aim of the study was to evaluate whether growth of small colorectal polyps left in situ is associated with specific molecular features.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-30T09:29:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003285","title":"Transcriptome sequencing of Gingivo-buccal Cancer : ICGC-India Project_Batch05","description":"Transcriptome Sequencing of Gingivo-buccal Cancer: ICGC-India ProjectAs a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India.   There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection.  Transcriptome sequencing of paired RNA samples – isolated from the tumor and adjacent normal tissues of 28 patients – have been performed. Detailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from adjacent normal and tumor tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai.  Sequencing is being performed at the National Institute of Biomedical Genomics, Kalyani.","abstract":"Transcriptome Sequencing of Gingivo-buccal Cancer: ICGC-India ProjectAs a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India.   There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection.  Transcriptome sequencing of paired RNA samples – isolated from the tumor and adjacent normal tissues of 28 patients – have been performed. Detailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from adjacent normal and tumor tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai.  Sequencing is being performed at the National Institute of Biomedical Genomics, Kalyani.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-30T10:47:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003286","title":"Androgen deprivation therapy promotes an inflammatory and obesity-like microenvironment in periprostatic fat","description":"Prostate cancer is a leading cause of cancer-related death and morbidity worldwide. Androgen deprivation therapy (ADT) is the cornerstone of management for advanced disease. The use of androgen deprivation therapies is associated with multiple side effects, including metabolic syndrome and truncal obesity. At the same time, obesity has been associated with both prostate cancer development and disease progression, linked to its effects on chronic inflammation at a tissue level. The connection between androgen deprivation therapy, obesity, inflammation, and prostate cancer progression is well-established in clinical settings; however, an understanding of the changes in adipose tissue at the molecular level induced by castrating therapies is missing. Here we investigated the transcriptional changes in periprostatic fat tissue induced by profound androgen deprivation therapy in a group of patients with high-risk tumours compared to a matching untreated cohort. We find that androgen deprivation therapy is associated with a pro-inflammatory and obesity-like adipose tissue microenvironment. This study suggests that the beneficial effect of androgen deprivation therapy may be partially counteracted by metabolic and inflammatory side effects in the adipose tissue surrounding the prostate.","abstract":"Prostate cancer is a leading cause of cancer-related death and morbidity worldwide. Androgen deprivation therapy (ADT) is the cornerstone of management for advanced disease. The use of androgen deprivation therapies is associated with multiple side effects, including metabolic syndrome and truncal obesity. At the same time, obesity has been associated with both prostate cancer development and disease progression, linked to its effects on chronic inflammation at a tissue level. The connection between androgen deprivation therapy, obesity, inflammation, and prostate cancer progression is well-established in clinical settings; however, an understanding of the changes in adipose tissue at the molecular level induced by castrating therapies is missing. Here we investigated the transcriptional changes in periprostatic fat tissue induced by profound androgen deprivation therapy in a group of patients with high-risk tumours compared to a matching untreated cohort. We find that androgen deprivation therapy is associated with a pro-inflammatory and obesity-like adipose tissue microenvironment. This study suggests that the beneficial effect of androgen deprivation therapy may be partially counteracted by metabolic and inflammatory side effects in the adipose tissue surrounding the prostate.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-10-31T13:06:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003287","title":"Time series analysis of neoadjuvant chemotherapy and bevacizumab treated breast carcinomas reveals a systemic shift in genomic aberrations","description":null,"abstract":"A phase II randomized clinical trial of 123 patients with Her2 negative breast cancer was conducted, with patients treated with neoadjuvant chemotherapy (fluorouracil (5FU)/epirubicin/cyclophosphamide (FEC) and taxane), with or without bevacizumab. \nA time course study to investigate the genomic landscape at the three time points; tumor DNA alterations, tumor percentage, genomic instability, and tumor clonality were assessed.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003288","title":"Mutated H3 Histones Drive Human Pre-Leukemic Hematopoietic Stem Cell Expansion And Promote Leukemic Aggressiveness","description":"Leukemogenesis is a stepwise progression from mutated, pre-neoplastic hematopoietic stem cells (HSCs) to full-blown leukemia. Our ability to prevent or treat acute myeloid leukemia (AML) is limited by our incomplete understanding of the epigenetic disruption that is central to this process, including improper histone methylation. Comprehensive analysis of 16 histone H3 genes in 434 primary AML samples identified Q69H, A26P, R2Q, R8H and K27M/I mutations (1.6%), and a higher incidence in secondary AML (s-AML) (9%). We establish that these mutations are important early events in leukemogenesis. They occur in pre-leukemic HSCs, increase the frequency of functional human HSCs, and alter differentiation. The mutations are present in the major leukemic clones in primary samples, and the mutant histones amplify leukemic aggressiveness with increased proliferation, expansion of leukemic progenitor and blast cells, and superior competitiveness in vivo. These effects are dependent on the specific mutation. Genome-wide analysis of K27 mutants revealed increased expression of genes involved in erythrocyte and myeloid differentiation with a corresponding decrease in histone H3 K27 tri-methylation and increase in K27 acetylation. The functional impact of histone mutations is independent of RUNX1 mutations, although they can co-occur. These data establish the involvement of H3 mutations as initial drivers of pre-cancerous stem cell expansion and leukemogenesis.","abstract":"Leukemogenesis is a stepwise progression from mutated, pre-neoplastic hematopoietic stem cells (HSCs) to full-blown leukemia. Our ability to prevent or treat acute myeloid leukemia (AML) is limited by our incomplete understanding of the epigenetic disruption that is central to this process, including improper histone methylation. Comprehensive analysis of 16 histone H3 genes in 434 primary AML samples identified Q69H, A26P, R2Q, R8H and K27M/I mutations (1.6%), and a higher incidence in secondary AML (s-AML) (9%). We establish that these mutations are important early events in leukemogenesis. They occur in pre-leukemic HSCs, increase the frequency of functional human HSCs, and alter differentiation. The mutations are present in the major leukemic clones in primary samples, and the mutant histones amplify leukemic aggressiveness with increased proliferation, expansion of leukemic progenitor and blast cells, and superior competitiveness in vivo. These effects are dependent on the specific mutation. Genome-wide analysis of K27 mutants revealed increased expression of genes involved in erythrocyte and myeloid differentiation with a corresponding decrease in histone H3 K27 tri-methylation and increase in K27 acetylation. The functional impact of histone mutations is independent of RUNX1 mutations, although they can co-occur. These data establish the involvement of H3 mutations as initial drivers of pre-cancerous stem cell expansion and leukemogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-01T14:29:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003289","title":"Synthetic_RNA_modulators_of_gene_function__a_pilot_study","description":"While the scale of GWAS, and number of discovered loci associated with traits has substantially increased over the past decade, functional validation, and understanding of underlying biology driving these associations has lagged behind; limiting translation of these discoveries into therapeutic applications. In this context, synthetic RNA modulators of gene function provide an efficient, and high-throughput mechanism for validation of discoveries in cellular models, providing a platform for interrogation and translation of findings from GWAS, into therapeutic applications within an integrated platform. An improvement in our understanding of the regulation of gene functions by different types of RNA modulators, and the technological development in the field of synthetic RNA molecules, has enabled high-throughput functional assays of cellular phenotypes in multiple cellular models, as well as opportunities to translate these discoveries directly into therapeutics. Complementary to this, recent development of deep learning approaches to effectively predict miRNA-target associations (Rayner et al., 2017) and promoter regions have provided a rich database of computationally predicted modulators of gene function for functional validation. We propose a high-throughput screen of 380 synthetic RNA molecules across 15 genes identified as associated with cardiometabolic and other traits through multiple lines of evidence (GWAS, eQTL, functional studies, and/or mouse phenotyping). We will use a range of synthetic RNA molecules to target a set of genes of interest in cellular models (HepG2 cell lines), to examine changes in target gene expression (efficacy), immunogenicity and cell-viability. Promoters will be identified through existing databases, and deep learning and bioinformatics approaches; we will also use predicted miRNA-target associations identified through deep learning frameworks trained on experimental evidence (Rayner et al., 2017), as part of an established collaboration. Alongside integrated genetic and EHR data, such datasets provide the opportunity to align multidimensional data to understand loci associated with disease, and identify potential therapeutic targets.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"While the scale of GWAS, and number of discovered loci associated with traits has substantially increased over the past decade, functional validation, and understanding of underlying biology driving these associations has lagged behind; limiting translation of these discoveries into therapeutic applications. In this context, synthetic RNA modulators of gene function provide an efficient, and high-throughput mechanism for validation of discoveries in cellular models, providing a platform for interrogation and translation of findings from GWAS, into therapeutic applications within an integrated platform. An improvement in our understanding of the regulation of gene functions by different types of RNA modulators, and the technological development in the field of synthetic RNA molecules, has enabled high-throughput functional assays of cellular phenotypes in multiple cellular models, as well as opportunities to translate these discoveries directly into therapeutics. Complementary to this, recent development of deep learning approaches to effectively predict miRNA-target associations (Rayner et al., 2017) and promoter regions have provided a rich database of computationally predicted modulators of gene function for functional validation. We propose a high-throughput screen of 380 synthetic RNA molecules across 15 genes identified as associated with cardiometabolic and other traits through multiple lines of evidence (GWAS, eQTL, functional studies, and/or mouse phenotyping). We will use a range of synthetic RNA molecules to target a set of genes of interest in cellular models (HepG2 cell lines), to examine changes in target gene expression (efficacy), immunogenicity and cell-viability. Promoters will be identified through existing databases, and deep learning and bioinformatics approaches; we will also use predicted miRNA-target associations identified through deep learning frameworks trained on experimental evidence (Rayner et al., 2017), as part of an established collaboration. Alongside integrated genetic and EHR data, such datasets provide the opportunity to align multidimensional data to understand loci associated with disease, and identify potential therapeutic targets.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003290","title":"Genomic characterization of metastatic breast cancers","description":"While large efforts have been done to characterize early breast cancer, little is known about the genomic landscape of metastatic breast cancer. In the present study, we performed whole exome sequencing of 629 metastatic breast cancers, in order to identify new candidate targets and better stratify patients eligible for innovative therapies.","abstract":"While large efforts have been done to characterize early breast cancer, little is known about the genomic landscape of metastatic breast cancer. In the present study, we performed whole exome sequencing of 629 metastatic breast cancers, in order to identify new candidate targets and better stratify patients eligible for innovative therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-05T13:29:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003291","title":"RNA sequencing of undifferentiated sarcomas","description":"Undifferentiated sarcomas (USARCs) of adults are diverse, rare, and aggressive soft tissue cancers. Recent sequencing efforts have confirmed that USARCs exhibit one of the highest burdens of structural aberrations across human cancer. Here, we sought to unravel the molecular basis of the structural complexity in USARCs by integrating DNA sequencing, ploidy analysis, gene expression, and methylation profiling. We identified whole genome duplication as a prevalent and pernicious force in USARC tumorigenesis. Using mathematical deconvolution strategies to unravel the complex copy-number profiles and mutational timing models we infer distinct evolutionary pathways of these rare cancers. In addition, 15% of tumors exhibited raised mutational burdens that correlated with gene expression signatures of immune infiltration, and good prognosis.","abstract":"Undifferentiated sarcomas (USARCs) of adults are diverse, rare, and aggressive soft tissue cancers. Recent sequencing efforts have confirmed that USARCs exhibit one of the highest burdens of structural aberrations across human cancer. Here, we sought to unravel the molecular basis of the structural complexity in USARCs by integrating DNA sequencing, ploidy analysis, gene expression, and methylation profiling. We identified whole genome duplication as a prevalent and pernicious force in USARC tumorigenesis. Using mathematical deconvolution strategies to unravel the complex copy-number profiles and mutational timing models we infer distinct evolutionary pathways of these rare cancers. In addition, 15% of tumors exhibited raised mutational burdens that correlated with gene expression signatures of immune infiltration, and good prognosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-05T16:43:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003292","title":"Whole Tumor spatial heterogeneity in metastatic melanoma","description":"Heterogeneous  inter-tumoral  responses,  sustained  periods  of  apparent  clinical  benefit  despite  lack  of objective response  to  various  therapies,  and  even  spontaneous  remission  are  well  known  within  a subpopulation of advanced melanoma patients. The molecular and cellular dynamics facilitating long-term survival  remain  poorly  defined,  particularly  in  the  current  era  ofexposure  to  multiple  potentially  active therapies. We studied an exceptional case of long-term survival in a patient with non-responding metastatic melanoma   in   order   to   characterize   the   clonal   and   microenvironmental   factors.We   performed immunogenomic analysis of 3 metachronous tumors, and of 67 intratumor sub-regions of one metastatic lesion,  usingwhole  exome  sequencing,  RNA-sequencing,  immunohistochemistry,  and  T  cell  receptor sequencing. Longitudinal analysesidentified mutations in severalknownresistance genes affecting distinctmetastases. Intra-tumoral immune signatures revealed spatially-distinct pockets of immune activation and suppression throughout the metastasis. A specific T cell VBeta CDR3 rearrangement was identified as both dominant and recurrent not only across multiple spatial points within a single tumor mass, but also across metachronous tumors spanning the patient’s disease course. Immunophenotyping of this T cell population with  single-cell  sequencingsuggestedrepeatedT-cell  priming  events  leading  to  the persistence  of  both activated and exhausted T cells bearing this same TCR-Beta at any given time.Our findings highlight genomic and  immune heterogeneityin  metastatic  disease,  extending  to  the  intra-tumoral  leveland  provide  a rationale for integrative spatiotemporal analysis of metastatic lesions in the context of immune checkpoint blockade.","abstract":"Heterogeneous  inter-tumoral  responses,  sustained  periods  of  apparent  clinical  benefit  despite  lack  of objective response  to  various  therapies,  and  even  spontaneous  remission  are  well  known  within  a subpopulation of advanced melanoma patients. The molecular and cellular dynamics facilitating long-term survival  remain  poorly  defined,  particularly  in  the  current  era  ofexposure  to  multiple  potentially  active therapies. We studied an exceptional case of long-term survival in a patient with non-responding metastatic melanoma   in   order   to   characterize   the   clonal   and   microenvironmental   factors.We   performed immunogenomic analysis of 3 metachronous tumors, and of 67 intratumor sub-regions of one metastatic lesion,  usingwhole  exome  sequencing,  RNA-sequencing,  immunohistochemistry,  and  T  cell  receptor sequencing. Longitudinal analysesidentified mutations in severalknownresistance genes affecting distinctmetastases. Intra-tumoral immune signatures revealed spatially-distinct pockets of immune activation and suppression throughout the metastasis. A specific T cell VBeta CDR3 rearrangement was identified as both dominant and recurrent not only across multiple spatial points within a single tumor mass, but also across metachronous tumors spanning the patient’s disease course. Immunophenotyping of this T cell population with  single-cell  sequencingsuggestedrepeatedT-cell  priming  events  leading  to  the persistence  of  both activated and exhausted T cells bearing this same TCR-Beta at any given time.Our findings highlight genomic and  immune heterogeneityin  metastatic  disease,  extending  to  the  intra-tumoral  leveland  provide  a rationale for integrative spatiotemporal analysis of metastatic lesions in the context of immune checkpoint blockade.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-05T18:41:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003293","title":"Pseudotime_ordering_of_cell_cycle_state","description":"We will be using G&amp;T method to sequence single cell genome and transcriptome derived from FS13B iPSCs cell line. The cell cycle state of each of the single cells is known. Hence, we will be analysing the genome and transcriptome of single cells from each of the cell cycle state to generate a copy number profile and transcriptome profile per given cell cycle stage: G1, S, G2, S.","abstract":"Currently, large scale single cell genome sequencing studies ignore cell cycle state, especially when preforming copy number analysis. In this study we aim to explore the level of heterogeneity caused by cell cycle state for copy number and transcriptome analysis. We will be using G&amp;T-seq method on single cells from FS13B iPSCs with known cell cycle state. We will generate a first draft of copy number and transcriptome profile of different cell stages: G1, S, G2 and M. The results will reveal the level of cell-to-cell heterogenity in DNA replication and enable the discovery of DNA replication programs of rare cells and will help to understand the replicaton-related DNA mutation.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-06T08:54:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003294","title":"CHOICE NSCLC Study","description":null,"abstract":"We sequenced 245 treatment naive Chinese NSCLC patients using Exome-seq and RNA-seq. The mutation profile was compared with TCGA results. The relationship between the immune cell composition in TME and tumor genomic alteration was investigated using the immune cell signatures.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003295","title":"SEARCH FOR BACTERIA IN NEURAL TISSUE FROM AMYOTROPHIC LATERAL SCLEROSIS","description":"The study aims to find bacteria in neural tissue from patients with amyotrophic lateral sclerosis","abstract":"The study aims to find bacteria in neural tissue from patients with amyotrophic lateral sclerosis","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-07T11:17:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003296","title":"1054 Flemish Gut Flora Project (FGFP) samples (16S sequencing, dual index)","description":"Study exploring the taxonomic component of the human gut microbiota in relation to quality of life and depression. This dataset includes 16S rRNA gene sequencing data from 1054 individuals from the Flanders region in Belgium. Microbiota covariates used in the study are provided.","abstract":"Study exploring the taxonomic component of the human gut microbiota in relation to quality of life and depression. This dataset includes 16S rRNA gene sequencing data from 1054 individuals from the Flanders region in Belgium. Microbiota covariates used in the study are provided.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-07T15:54:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003297","title":"Placental_genomics","description":"The aim of this study is to define the mutational landscape of placentas.","abstract":"The aim of this study is to define the mutational landscape of placentas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-08T12:06:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003298","title":"FGFP and TR-MDD shotgun sequencing samples (N=157)","description":"Study exploring the neuroactive potential of the human gut microbiota in relation to quality of life and depression. This dataset includes shotgun sequenced samples from the FGFP (Flemish Gut Flora Project: N=150) and TR-MDD (Treatment-Resistant Major Depression Disorder: N=7). Samples were provided by volunteers from the Flanders region in Belgium, and the dataset is balanced for age, gender, and stool consistency.","abstract":"Study exploring the neuroactive potential of the human gut microbiota in relation to quality of life and depression. This dataset includes shotgun sequenced samples from the FGFP (Flemish Gut Flora Project: N=150) and TR-MDD (Treatment-Resistant Major Depression Disorder: N=7). Samples were provided by volunteers from the Flanders region in Belgium, and the dataset is balanced for age, gender, and stool consistency.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-08T13:47:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003299","title":"PTPN22 SNPs and outcome on lung transplantation","description":null,"abstract":"Obstructive chronic lung allograft dysfunction (BOS) is the major limiting factor for lung transplantation (LTx) outcome. PTPN22 is described as the hallmark autoimmunity gene, and one specific single nucleotide polymorphism (SNP), rs2476601, is associated with multiple autoimmune diseases, impaired T cell regulation and autoantibody formation. Taking into consideration the contribution of autoimmunity to LTx outcome, we hypothesized that polymorphisms in the PTPN22 gene could be associated with BOS incidence. We selected six SNPs within PTPN22 and analyzed both patient and donor genotypes on BOS development post-LTx.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003300","title":"Acquiring and sequencing of all 24 single human chromosomes","description":"Haplotype phased whole genome sequencing of individuals is a technical challenge when family members are unavailable for determining chromosome of origin and variant linkage. Completely phasing genome sequences with single chromosomes has been shown to be feasible however amplifying all the single chromosomes for subsequent whole genome sequencing has been proposed but not performed to date. We acquired single chromosome of one of each of the autosomes and sex chromosomes to assess the feasibility of this sequencing library template preparation process.","abstract":"Haplotype phased whole genome sequencing of individuals is a technical challenge when family members are unavailable for determining chromosome of origin and variant linkage. Completely phasing genome sequences with single chromosomes has been shown to be feasible however amplifying all the single chromosomes for subsequent whole genome sequencing has been proposed but not performed to date. We acquired single chromosome of one of each of the autosomes and sex chromosomes to assess the feasibility of this sequencing library template preparation process.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-09T14:41:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003301","title":"do not use (deleted)","description":"deleted","abstract":"deleted","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003302","title":"Tetralogy of fallot whole-exome sequencing","description":"829 adult and child probands of Northern European ancestry presenting with TOF were recruited from nine centres: seven in the UK, Leuven (Belgium), and Sydney (Australia). Patients sequenced exhibited no clinical features of recognised syndromes, extra-cardiac abnormalities or learning difficulties. All samples were screened for the 22q11.2 deletion associated with TOF prior to sequencing to ensure that this was not present. Samples were sequenced on HiSeq2000 and reads aligned using BWA.","abstract":"829 adult and child probands of Northern European ancestry presenting with TOF were recruited from nine centres: seven in the UK, Leuven (Belgium), and Sydney (Australia). Patients sequenced exhibited no clinical features of recognised syndromes, extra-cardiac abnormalities or learning difficulties. All samples were screened for the 22q11.2 deletion associated with TOF prior to sequencing to ensure that this was not present. Samples were sequenced on HiSeq2000 and reads aligned using BWA.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001003303","title":"Genetic alterations in metastatic uveal melanoma","description":null,"abstract":"Targeted sequencing of primary uveal melanoma and their matched metastases.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-11T21:10:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003304","title":"Neoadjuvant chemotherapy alters the genomic landscape and immune  microenvironment of breast cancers","description":"To characterize the effects of neoadjuvant chemotherapy (NAC) on the genome, transcriptome and tumor infiltrating leukocytes (TILs), we have conducted whole exome and whole transcriptome sequencing of a comprehensive, longitudinal breast cancer cohort consisting of 146 cases and 281 paired tumor samples. In total, 52 (38%) patients achieved pathologic complete response (pCR) while 85 patients (62%) had\nresidual disease with standard chemotherapy regimen. Tumor biopsies were collected for each patient at three time points – pre-treatment, three weeks after the first cycle of anthracycline and cyclophosphamide (AC) and at the time of surgery after 3 more cycles of AC followed by 4 cycles of taxane or taxane plus Herceptin in case of HER2+ subtype.","abstract":"To characterize the effects of neoadjuvant chemotherapy (NAC) on the genome, transcriptome and tumor infiltrating leukocytes (TILs), we have conducted whole exome and whole transcriptome sequencing of a comprehensive, longitudinal breast cancer cohort consisting of 146 cases and 281 paired tumor samples. In total, 52 (38%) patients achieved pathologic complete response (pCR) while 85 patients (62%) had\nresidual disease with standard chemotherapy regimen. Tumor biopsies were collected for each patient at three time points – pre-treatment, three weeks after the first cycle of anthracycline and cyclophosphamide (AC) and at the time of surgery after 3 more cycles of AC followed by 4 cycles of taxane or taxane plus Herceptin in case of HER2+ subtype.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003305","title":"Whole genome sequencing of tumour and matched normal from patients with family history of breast cancer","description":"Analysis of whole genome sequencing of tumour and matched normal from familial breast cancer patients who had previously undergone clinical germline testing for variation in the BRCA1 and BRCA2 genes. The patients were either carriers of BRCA1 or BRCA2 germline pathogenic variants or non-carriers high-risk individuals (non-BRCA1/2). Somatic mutational signatures were used to study tumour aetiology of these individuals.","abstract":"Analysis of whole genome sequencing of tumour and matched normal from familial breast cancer patients who had previously undergone clinical germline testing for variation in the BRCA1 and BRCA2 genes. The patients were either carriers of BRCA1 or BRCA2 germline pathogenic variants or non-carriers high-risk individuals (non-BRCA1/2). Somatic mutational signatures were used to study tumour aetiology of these individuals.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-13T03:13:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003306","title":"Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer","description":"The goal of the sequencing study was to determine the neoantigen profile of melanoma patients. We performed whole exome sequening of the tumor and respective patien matched PBMC samples (2x50nt) and RNA-sqeuencing of the tumor samples. The was analyzed for somatic point mutaions, using the RNA-Seq data to determine mutation expression. This study contains the exome seq data.","abstract":"The goal of the sequencing study was to determine the neoantigen profile of melanoma patients. We performed whole exome sequening of the tumor and respective patien matched PBMC samples (2x50nt) and RNA-sqeuencing of the tumor samples. The was analyzed for somatic point mutaions, using the RNA-Seq data to determine mutation expression. This study contains the exome seq data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-13T10:16:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003307","title":"Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer RNA-Seq","description":"The goal of the sequencing study was to determine the neoantigen profile of melanoma patients. We performed whole exome sequening of the tumor and respective patien matched PBMC samples (2x50nt) and RNA-sqeuencing of the tumor samples. The was analyzed for somatic point mutaions, using the RNA-Seq data to determine mutation expression. This study contains the patient matched RNA-Sequencing data.","abstract":"The goal of the sequencing study was to determine the neoantigen profile of melanoma patients. We performed whole exome sequening of the tumor and respective patien matched PBMC samples (2x50nt) and RNA-sqeuencing of the tumor samples. The was analyzed for somatic point mutaions, using the RNA-Seq data to determine mutation expression. This study contains the patient matched RNA-Sequencing data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-13T10:16:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003308","title":"mtDNA variability of the Polish population","description":null,"abstract":"The aim of the present study was to define the mtDNA variability of Polish population. For the first time, the study of Polish population was conducted on such a large number of individuals (5800) representing administrative units of both levels of local administration in Poland (voivodeships and counties). Furthermore, the clusters were used as an additional form of population subdivision, corresponding to geographic regions of Poland.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003309","title":"The analysis of mtDNA variability of the modern Polish population","description":"The aim of the present study was to define the mtDNA variability of Polish population. For the first time, the study of Polish population was conducted on such a large number of individuals (n=5800) representing administrative units of both levels of local administration in Poland (voivodeships and counties). Furthermore, the clusters were used as an additional form of population subdivision, corresponding to geographic regions of Poland.","abstract":"The aim of the present study was to define the mtDNA variability of Polish population. For the first time, the study of Polish population was conducted on such a large number of individuals (n=5800) representing administrative units of both levels of local administration in Poland (voivodeships and counties). Furthermore, the clusters were used as an additional form of population subdivision, corresponding to geographic regions of Poland.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-13T13:27:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003310","title":"Adeno-associated virus in the liver: natural history and consequences in tumor development","description":"Adeno-associated virus (AAV) is a defective mono-stranded DNA virus, endemic in human population (40-80%). AAV infection has long been considered as non-pathogenic1, however few years ago we reported for the first time recurrent clonal AAV2 insertion in the pathogenesis of human hepatocellular carcinoma (HCC) developed on normal liver. These clonal viral insertions target cancer driver genes, including CCNA2, CCNE1, TERT, TNFSF10 and MLL4, leading to their overexpression. The viral inserted sequences involved in almost all the cases the 3’ inverse tandem repeat (ITR) of AAV2, which is important for virus integration in host DNA and exhibits a promoter/enhancer activity. Here, we used RNA sequencing (RNA-seq) to investigate their functional impact on the tissue, such as fusion transcript generation events.","abstract":"Adeno-associated virus (AAV) is a defective mono-stranded DNA virus, endemic in human population (40-80%). AAV infection has long been considered as non-pathogenic1, however few years ago we reported for the first time recurrent clonal AAV2 insertion in the pathogenesis of human hepatocellular carcinoma (HCC) developed on normal liver. These clonal viral insertions target cancer driver genes, including CCNA2, CCNE1, TERT, TNFSF10 and MLL4, leading to their overexpression. The viral inserted sequences involved in almost all the cases the 3’ inverse tandem repeat (ITR) of AAV2, which is important for virus integration in host DNA and exhibits a promoter/enhancer activity. Here, we used RNA sequencing (RNA-seq) to investigate their functional impact on the tissue, such as fusion transcript generation events.","study_type":"Other","pubmed_ids":[31375600],"external_links":null,"is_released":true,"released_date":"2018-11-13T16:37:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003311","title":"MutWP5__CRUK_Mutographs_of_Cancer__Breast__Reduction_Mammoplasty__WG_","description":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-14T15:49:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003312","title":"MutWP5__CRUK_Mutographs_of_Cancer__Breast__Reduction_Mammoplasty__Targeted_","description":"Sequencing of LCM-derived microbiopsies from 10 women who underwent reduction mammoplasty. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Targeted data will be used as a driver and clonality screen, highly clonal or driver-containing samples will subsequently be sent for whole-genome sequencing. Results from this portion of the study will be compared to women who are BRCA1/2 germline carriers and those with cancer.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003313","title":"MutWP5__CRUK_Mutographs_of_Cancer__Breast__Reduction_Mammoplasty__Exome_","description":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-14T15:56:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003314","title":"MutWP5__CRUK_Mutographs_of_Cancer__Breast__BRCA_Carriers__WG_","description":"Sequencing of LCM-derived microbiopsies from 20 women who underwent risk-reducing reduction mastecomies due to germline BRCA1/2. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Whole-genome sequencing will be conducted on samples identified as promising from the initial targeted data. Results from this portion of the study will be compared to women who had cosmetic breast reduction surgeries and those who are cancer patients.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003315","title":"MutWP5__CRUK_Mutographs_of_Cancer__Breast__BRCA_Carriers__Targeted_","description":"Sequencing of LCM-derived microbiopsies from 20 women who underwent risk-reducing reduction mastectomies due to germline BRCA1/2. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Targeted data will be used as a driver and clonality screen, highly clonal or driver-containing samples will subsequently be sent for whole-genome sequencing. Results from this portion of the study will be compared to women who had cosmetic breast reduction surgeries and those with cancer.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-14T16:03:18+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003316","title":"MutWP5__CRUK_Mutographs_of_Cancer__Breast__BRCA_Carriers__Exome_","description":"Sequencing of LCM-derived microbiopsies from 20 women who underwent risk-reducing reduction mastectomies due to germline BRCA1/2. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Exome data will be used as a driver and clonality screen, highly clonal or driver-containing samples will subsequently be sent for whole-genome sequencing. Results from this portion of the study will be compared to women who had cosmetic breast reduction surgeries and those with cancer.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-14T16:06:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003317","title":"MutWP5__CRUK_Mutographs_of_Cancer__Breast__Cancer_Mastectomy__WG_","description":"Sequencing of LCM-derived microbiopsies from 40 women who underwent mastectomies due to breast cancer. LCM and sequencing will be conducted on both normal, unaffected breast, and, where possible, tumour tissue. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue, and compare findings between the normal and associated cancer tissues. Whole-genome sequencing will be conducted on samples identified as promising from the initial targeted data. Results from this portion of the study will be compared to women who had cosmetic breast reduction surgeries and those who are BRCA carriers.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-14T16:09:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003318","title":"MutWP5__CRUK_Mutographs_of_Cancer__Breast__Cancer_Mastectomy__Targeted_","description":"Sequencing of LCM-derived microbiopsies from 30 women who mastectomies due to Breast Cancer. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Targeted data will be used as a driver and clonality screen, highly clonal or driver-containing samples will subsequently be sent for whole-genome sequencing. Results from this portion of the study will be compared to women who had cosmetic breast reduction surgeries and those with germline BRCA 1/2 mutations.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-14T16:13:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003319","title":"MutWP5__CRUK_Mutographs_of_Cancer__Breast__Cancer_Mastectomy__Exome_","description":"Sequencing of LCM-derived microbiopsies from 30 women who underwent mastectomies due to a breast cancer diagnosis. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Exome data will be used as a driver and clonality screen, highly clonal or driver-containing samples will subsequently be sent for whole-genome sequencing. Results from this portion of the study will be compared to women who had cosmetic breast reduction surgeries and those with germline BRCA 1/2 mutations.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-14T16:16:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003320","title":"MutWP5__CRUK_Mutographs_of_Cancer__Lung__PD37920__WG_","description":"Sequencing of LCM-derived microbiopsies from explanted lung from COPD patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Whole-genome sequencing will be conducted on samples identified as promising from the initial targeted data. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from lung tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will deeply sample from individuals with smoking-related lung diseases (COPD, pulmonary fibrosis, lung cancer) and those without smoking history. This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-14T16:27:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003321","title":"MutWP5__CRUK_Mutographs_of_Cancer__Lung__PD37920__Targeted_","description":"Sequencing of LCM-derived microbiopsies from explanted lung from COPD patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Targeted sequencing will be conducted on samples to identify drivers of interest and clonality of the samples, well-performing samples will be sent for subsequent whole-genome sequencing. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from lung tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will deeply sample from individuals with smoking-related lung diseases (COPD, pulmonary fibrosis, lung cancer) and those without smoking history. This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-14T16:30:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003322","title":"MutWP5__CRUK_Mutographs_of_Cancer__Lung__PD38233__WG_","description":"Sequencing of LCM-derived microbiopsies from explanted lung from COPD patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Whole-genome sequencing will be conducted on samples identified as promising from the initial targeted data. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from lung tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will deeply sample from individuals with smoking-related lung diseases (COPD, pulmonary fibrosis, lung cancer) and those without smoking history. This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-14T16:33:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003323","title":"MutWP5__CRUK_Mutographs_of_Cancer__Lung__PD38233__Targeted_","description":"Sequencing of LCM-derived microbiopsies from explanted lung from COPD patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Targeted sequencing will be conducted on samples to identify drivers of interest and clonality of the samples, well-performing samples will be sent for subsequent whole-genome sequencing. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from lung tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will deeply sample from individuals with smoking-related lung diseases (COPD, pulmonary fibrosis, lung cancer) and those without smoking history. This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003324","title":"MutWP5__CRUK_Mutographs_of_Cancer__Lung__PD38234__WG_","description":"Sequencing of LCM-derived microbiopsies from explanted lung from pulmonary fibrosis patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Whole-genome sequencing will be conducted on samples identified as promising from the initial targeted data. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from lung tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will deeply sample from individuals with smoking-related lung diseases (COPD, pulmonary fibrosis, lung cancer) and those without smoking history. This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-14T16:39:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003325","title":"MutWP5__CRUK_Mutographs_of_Cancer__Lung__PD38234__Targeted_","description":"Sequencing of LCM-derived microbiopsies from explanted lung from pulmonary fibrosis patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Targeted sequencing will be conducted on samples to identify drivers of interest and clonality of the samples, well-performing samples will be sent for subsequent whole-genome sequencing. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from lung tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will deeply sample from individuals with smoking-related lung diseases (COPD, pulmonary fibrosis, lung cancer) and those without smoking history. This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-14T16:41:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003326","title":"MutWP5__CRUK_Mutographs_of_Cancer__Lung__PD39464__WG_","description":"Sequencing of LCM-derived microbiopsies from explanted lung from COPD patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Whole-genome sequencing will be conducted on samples identified as promising from the initial targeted data. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from lung tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will deeply sample from individuals with smoking-related lung diseases (COPD, pulmonary fibrosis, lung cancer) and those without smoking history. This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003327","title":"MutWP5__CRUK_Mutographs_of_Cancer__Lung__PD39464__Targeted_","description":"Sequencing of LCM-derived microbiopsies from explanted lung from COPD patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Targeted sequencing will be conducted on samples to identify drivers of interest and clonality of the samples, well-performing samples will be sent for subsequent whole-genome sequencing. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from lung tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will deeply sample from individuals with smoking-related lung diseases (COPD, pulmonary fibrosis, lung cancer) and those without smoking history. This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003328","title":"Extreme down-regulation of chromosome Y and male disease","description":null,"abstract":"Mosaic loss of chromosome Y (LOY) in blood has been associated to all-cause mortality in men. However, it is unknown whether LOY in affected tissues precedes disease. We identified a subgroup of cancer patients with EDY (extreme down-regulation of chromosome Y) and no LOY characterized by decreased survival and increased copy number duplicationscontaining EGFR abd MDM2. Our analyses support EDY as a novel risk factor of male disease, which can be triggered by different factors including LOY.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003329","title":"H014: HES5 mediates NOTCH signaling by interaction with AKT to drive liver carcinogenesis","description":"Notch signaling plays a pivotal role in liver development and aberrant Notch signaling may lead to hepatocellular (HCC) or cholangiocellular carcinoma (CCA) development. Using whole exome sequencing of 54 human HCC samples, we discovered 19 somatic missense mutations in 15 different Notch pathway genes affecting 24.6% (14 of 57) of patients. Prediction of functional impact of these Notch pathway mutations revealed HES5-R31G to have high relevance. We found HES5 to be strongly activated by Notch signaling. In vitro, HES5 reduced cell migration and clonogenicity and in vivo, HES5 inhibited MYC-dependent liver tumor formation. But together with AKT, HES5 increased liver tumor formation in a mouse model. HES5 directly binds to AKT and AKT expression leads to increase HES5 protein levels. Furthermore, HES5 exhibits a negative feed-back loop by inhibiting NOTCH1 and HES1 gene expression. In contrast, HES5-R31G appears to be non-functional possibly by loss of nuclear translocation","abstract":"Notch signaling plays a pivotal role in liver development and aberrant Notch signaling may lead to hepatocellular (HCC) or cholangiocellular carcinoma (CCA) development. Using whole exome sequencing of 54 human HCC samples, we discovered 19 somatic missense mutations in 15 different Notch pathway genes affecting 24.6% (14 of 57) of patients. Prediction of functional impact of these Notch pathway mutations revealed HES5-R31G to have high relevance. We found HES5 to be strongly activated by Notch signaling. In vitro, HES5 reduced cell migration and clonogenicity and in vivo, HES5 inhibited MYC-dependent liver tumor formation. But together with AKT, HES5 increased liver tumor formation in a mouse model. HES5 directly binds to AKT and AKT expression leads to increase HES5 protein levels. Furthermore, HES5 exhibits a negative feed-back loop by inhibiting NOTCH1 and HES1 gene expression. In contrast, HES5-R31G appears to be non-functional possibly by loss of nuclear translocation","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-15T12:19:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003330","title":"HG_Diversity_and_selection_in_the_ancient_Near_East","description":"Sequencing of ancient individuals from Beirut dating back to the Roman Period\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We aim to study the genetic diversity of ancient Near Easterners by sequencing the genomes of 30 individuals who lived during the Roman Period in Lebanon.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003331","title":"SNP array datas of 'Matched' cancer/PNE","description":"SNP array data of 31 Matched cancer/PNE samples","abstract":"SNP array data of 31 Matched cancer/PNE samples","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-15T16:46:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003332","title":"RNAseq data from human colon organoid infected by KP","description":"The aim of this study is to identify the specific bacteria that are responsible for pathological bacterial translocation and subsequent Th17 priming in the liver in primary sclerosing cholangitis (PSC). To clarify the mechanism of how microbiota interacts with the intestinal epithelial barrier, monolayered human intestinal organoids were cultured with the specific bacteria. Gene expression analysis using RNA sequencing in epithelial cells cultured with Klebsiella pneumoniae derived from a PSC patient (KP-P1) or commercially obtained Klebsiella pneumoniae strain (KP JCM1662) was performed in this study.","abstract":"The aim of this study is to identify the specific bacteria that are responsible for pathological bacterial translocation and subsequent Th17 priming in the liver in primary sclerosing cholangitis (PSC). To clarify the mechanism of how microbiota interacts with the intestinal epithelial barrier, monolayered human intestinal organoids were cultured with the specific bacteria. Gene expression analysis using RNA sequencing in epithelial cells cultured with Klebsiella pneumoniae derived from a PSC patient (KP-P1) or commercially obtained Klebsiella pneumoniae strain (KP JCM1662) was performed in this study.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-16T08:20:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003333","title":"RNA-seq of Ewing sarcoma tumors (ICGC)","description":"Ewing sarcoma (ES) is a primary bone tumor initiated by an EWSR1-ETS gene fusion. To characterize the transcriptome of Ewing sarcoma, RNA-seq was performed.","abstract":"Ewing sarcoma (ES) is a primary bone tumor initiated by an EWSR1-ETS gene fusion. To characterize the transcriptome of Ewing sarcoma, RNA-seq was performed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-19T09:58:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003334","title":"Naive B-cell receptor heavy chain repertoire of celiac patients and healthy controls.","description":"We sequenced the naïve B-cell IGH repertoire of 100 individuals. Approximately half of the individuals enrolled in the study have celiac disease (n=52) and the others are controls (n=48).","abstract":"We sequenced the naïve B-cell IGH repertoire of 100 individuals. Approximately half of the individuals enrolled in the study have celiac disease (n=52) and the others are controls (n=48).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003335","title":"Genome-wide characterization of Arabian Peninsula populations","description":"The screening of 741,000 variants in 420 individuals from Arabian Peninsula (100 from Saudi Arabia, 100 from Yemen, 100 from Oman and 120 from UAE) and 80 individuals from Iran.","abstract":"The screening of 741,000 variants in 420 individuals from Arabian Peninsula (100 from Saudi Arabia, 100 from Yemen, 100 from Oman and 120 from UAE) and 80 individuals from Iran.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-21T12:06:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003336","title":"Whole Exome Sequencing of neuroblastoma cell lines with ALK mutations","description":"We have studied two neuroblastoma cell lines established from a stage 4 patient at diagnosis either from the primary tumor (CLB-MA PT) or from the bone marrow (CLB-MA BM). Our work documented the dynamics of two ALK activating mutations, L1196M and F1174L, in the CLB-MA PT cell line during cell culture. This study includes WES data for the CLB-MA BM cell line as well as for the CLB-MA PT cell line at passage 3, 6 and 10 (first cell batch).","abstract":"We have studied two neuroblastoma cell lines established from a stage 4 patient at diagnosis either from the primary tumor (CLB-MA PT) or from the bone marrow (CLB-MA BM). Our work documented the dynamics of two ALK activating mutations, L1196M and F1174L, in the CLB-MA PT cell line during cell culture. This study includes WES data for the CLB-MA BM cell line as well as for the CLB-MA PT cell line at passage 3, 6 and 10 (first cell batch).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003337","title":"Naive B-cell receptor heavy chain repertoire of celiac patients and healthy controls","description":null,"abstract":"We sequenced the naïve B-cell IGH repertoire of 100 individuals. Approximately half of the individuals enrolled in the study have celiac disease (n=52) and the others are controls (n=48).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-21T14:48:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003338","title":"MutWP6__CRUK_Grand_Challenge_Mutographs_of_Cancer__aristolochic_acid_","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nWithin Mutographs, work lead by the Sanger Institute will investigate whether detection of somatic mutations and mutational signatures in circulating white blood cells can be developed into a practical, generic system for surveying and monitoring multiple different endogenous and exogenous exposures, providing an ‘observatory’ on somatic mutational processes in humans.\n\nWhole genome sequences are generated at the Wellcome Sanger Institute (Illumina HiSeqX). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nWithin Mutographs, work lead by the Sanger Institute will investigate whether detection of somatic mutations and mutational signatures in circulating white blood cells can be developed into a practical, generic system for surveying and monitoring multiple different endogenous and exogenous exposures, providing an ‘observatory’ on somatic mutational processes in humans.\n\nWhole genome sequences are generated at the Wellcome Sanger Institute (Illumina HiSeqX). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003339","title":"Comprehensive genetic analysis of uveal melanoma heterogeneity during metastatic progression","description":null,"abstract":"Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Despite improvement of diagnosis and treatment of the primary tumor, there is no effective treatment of metastatic disease and approximately half of patients will die within one year or less following metastases detection. Tumor heterogeneity has been proposed as a key factor of drug resistance. However, it has been scarcely studied in UM. The present project aims searching for specific drivers of the metastatic progression, describing the genomic and transcriptomic landscape of metastatic UM, exploring tumor heterogeneity and investigating its role in drug resistance. Thus whole exome sequencing and transcriptomics have been performed on constitutional, primary tumor and metastatic samples from 28 UM patients.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003340","title":"Early detection of metastatic relapse and monitoring of therapeutic efficacy by ultra-deep sequencing of plasma cell-free DNA in patients with urothelial bladder carcinoma","description":null,"abstract":"The use of circulating tumor DNA (ctDNA) as a biomarker for disease staging at diagnosis, tumor burden, early detection of metastatic relapse, disease surveillance and therapeutic treatment response is an emerging field in multiple cancer types. We document that ctDNA is a powerful biomarker for prognosis and early detection of metastatic disease. Furthermore, we show that ctDNA dynamics during treatment is a predictor of chemotherapy response and patient outcome.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003341","title":"MGA-NUTM1 fusion in high grade spindle cell sarcoma","description":"NUT carcinoma (NC) with mesenchymal differentiation have rarely been described in the literature. In this report, we describe the characterization of two cases of high grade spindle cell sarcoma harboring a novel MGA-NUTM1 fusion. Whole genome sequencing identified the presence of complex rearrangements resulting in a MGA-NUTM1 fusion gene in the absence of other significant somatic mutations. The fusion protein was predicted to retain nearly the entire protein sequence of both MGA (exons 1-22) and NUTM1 (exons 3-8). In contrast to typical cases of NC, these cases were successfully treated with aggressive local control measures (surgery and radiation) and both patients remain alive without disease. These cases describe a new subtype of NUTM1-rearranged tumors warranting expansion of diagnostic testing to evaluate for the presence of MGA-NUTM1 or alternative NUTM1 gene fusions in the diagnostic workup of high grade spindle cell sarcomas or small round blue cell tumors of ambiguous lineage.","abstract":"NUT carcinoma (NC) with mesenchymal differentiation have rarely been described in the literature. In this report, we describe the characterization of two cases of high grade spindle cell sarcoma harboring a novel MGA-NUTM1 fusion. Whole genome sequencing identified the presence of complex rearrangements resulting in a MGA-NUTM1 fusion gene in the absence of other significant somatic mutations. The fusion protein was predicted to retain nearly the entire protein sequence of both MGA (exons 1-22) and NUTM1 (exons 3-8). In contrast to typical cases of NC, these cases were successfully treated with aggressive local control measures (surgery and radiation) and both patients remain alive without disease. These cases describe a new subtype of NUTM1-rearranged tumors warranting expansion of diagnostic testing to evaluate for the presence of MGA-NUTM1 or alternative NUTM1 gene fusions in the diagnostic workup of high grade spindle cell sarcomas or small round blue cell tumors of ambiguous lineage.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-22T14:56:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003342","title":"WGS and WES of pediatric osteosarcoma","description":"Despite being the most common childhood bone tumor, the genomic characterization of osteosarcoma remains incomplete. Very few metastatic cases have been sequenced to date, a required step to better understand the progression and evolution of this tumor. Here, we present an integrative analysis of whole genome and whole exome sequencing (WGS and WES) of a cohort of primary and metastatic pediatric osteosarcoma, in order to identify recurrent genomic alterations between and within patients.","abstract":"Despite being the most common childhood bone tumor, the genomic characterization of osteosarcoma remains incomplete. Very few metastatic cases have been sequenced to date, a required step to better understand the progression and evolution of this tumor. Here, we present an integrative analysis of whole genome and whole exome sequencing (WGS and WES) of a cohort of primary and metastatic pediatric osteosarcoma, in order to identify recurrent genomic alterations between and within patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-22T16:52:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003343","title":"Exome sequencing of a novel cervical cancer cell line","description":"Human cancer cell lines are largely used in the searching for new antineoplastic agents. However, due to the artifacts of a long-term in culture, cell lines do not always represent the realistic tumor cell behavior. This has motivated the development of models that better mimetics the tumor tissue, among them, the establishment of primary cell cultures. In this work, we establish and characterized a low-passage cervix cancer cell line from a Brazilian patient with squamous cell carcinoma. The phenotype confirms the epithelial and tumor origin, through cytokeratins, EpCAM, and p16 staining. Whole exome sequencing showed relevant somatic mutations in several genes including BRCA2, TGFBR1, and IRX2 genes. CNV analysis by nanostring and WGS revealed amplification in genes related mainly with kinases proteins, involved in proliferation, migration and cell differentiation, such as EGFR, PIK3CA, and MAPK7. Overexpression of EGFR was confirmed by phospho RTK-array and western blot analysis. Furthermore, the cell was sensitivity to cisplatin, with IC50 13 times lower than SiHa cell line. In conclusion, this cervical cancer cell line presents molecular alterations that are an important tool for leading pre-clinical studies of new drugs that target one or more of the altered pathways.","abstract":"Human cancer cell lines are largely used in the searching for new antineoplastic agents. However, due to the artifacts of a long-term in culture, cell lines do not always represent the realistic tumor cell behavior. This has motivated the development of models that better mimetics the tumor tissue, among them, the establishment of primary cell cultures. In this work, we establish and characterized a low-passage cervix cancer cell line from a Brazilian patient with squamous cell carcinoma. The phenotype confirms the epithelial and tumor origin, through cytokeratins, EpCAM, and p16 staining. Whole exome sequencing showed relevant somatic mutations in several genes including BRCA2, TGFBR1, and IRX2 genes. CNV analysis by nanostring and WGS revealed amplification in genes related mainly with kinases proteins, involved in proliferation, migration and cell differentiation, such as EGFR, PIK3CA, and MAPK7. Overexpression of EGFR was confirmed by phospho RTK-array and western blot analysis. Furthermore, the cell was sensitivity to cisplatin, with IC50 13 times lower than SiHa cell line. In conclusion, this cervical cancer cell line presents molecular alterations that are an important tool for leading pre-clinical studies of new drugs that target one or more of the altered pathways.","study_type":"Other","pubmed_ids":[30760827],"external_links":null,"is_released":true,"released_date":"2018-11-23T13:06:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003344","title":"CAF-S3 subset in human breast and ovarian cancers","description":"Carcinoma-associated fibroblasts (CAF) are key players in the tumor microenvironment. By combining 6 well-known stromal markers, we identify four CAF subsets (CAF-S1 to CAF-S4) in human breast and ovarian cancers.","abstract":"Carcinoma-associated fibroblasts (CAF) are key players in the tumor microenvironment. By combining 6 well-known stromal markers, we identify four CAF subsets (CAF-S1 to CAF-S4) in human breast and ovarian cancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-26T09:22:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003345","title":"Small intestinal plasma cells transcriptome profiles","description":"Objective: Plasma cells (PCs) are terminally differentiated B-lymphocytes that produce antibodies. The lamina propria of the small intestine is particularly rich in PCs. In coeliac disease (CeD) there is infiltration and increased density of PCs in the small intestinal lesion. Many of these PCs produce disease-specific autoantibodies targeting the enzyme transglutaminase 2 (TG2). The plasmacytosis and high numbers of disease-antigen reactive PCs in CeD motivated us to study the transcriptional programme of PCs from coeliac gut lesions. \n\nDesign: We performed RNASeq analysis of IgA+ PCs of untreated CeD patients being specific or non-specific for TG2 and from healthy controls.","abstract":"Objective: Plasma cells (PCs) are terminally differentiated B-lymphocytes that produce antibodies. The lamina propria of the small intestine is particularly rich in PCs. In coeliac disease (CeD) there is infiltration and increased density of PCs in the small intestinal lesion. Many of these PCs produce disease-specific autoantibodies targeting the enzyme transglutaminase 2 (TG2). The plasmacytosis and high numbers of disease-antigen reactive PCs in CeD motivated us to study the transcriptional programme of PCs from coeliac gut lesions. \n\nDesign: We performed RNASeq analysis of IgA+ PCs of untreated CeD patients being specific or non-specific for TG2 and from healthy controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-26T09:36:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003346","title":"HG Transcriptome sequencing in the INTERVAL cohort","description":"We performed bulk RNA-sequencing on peripheral blood collected from 4,732\nblood donors recruited as part of the INTERVAL study. Using these data, we\nmapped gene expression and splicing quantitative trait loci (QTLs). Then,\nwe integrated these data with protein, metabolite and lipid QTLs in the\nsame individuals. The study aimed to identify the shared genetic etiology\nacross transcriptional phenotypes, molecular traits and health outcomes in\nhumans.","abstract":"We performed bulk RNA-sequencing on peripheral blood collected from 4,732\nblood donors recruited as part of the INTERVAL study. Using these data, we\nmapped gene expression and splicing quantitative trait loci (QTLs). Then,\nwe integrated these data with protein, metabolite and lipid QTLs in the\nsame individuals. The study aimed to identify the shared genetic etiology\nacross transcriptional phenotypes, molecular traits and health outcomes in\nhumans.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-26T14:25:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003347","title":"Genome_wide_CRISPR_Cas9_screening_of_Human_Organoid_Lines","description":"The study will perform genome-wide loss-of-function CRISPR-Cas9 screens across genetically annotated human organoid lines to idenify sythetic-lethal interaction between cancer genomes and targeted gene deletions.\n\n*Sequencing is performed on PCR products from the amplification of gRNA segments introduced into commercial cell lines. Cellular DNA or RNA are not sequenced. This data is defined as \"Other Biological/Biochemical Assay Data\" under the WTSI datasharing guidelines and consequently will be released at the time of publication and/or through faculty websites.","abstract":"The goal of this project is to perform genome-wide loss-of-function CRISPR-Cas9 screens across genetically annotated human organoid lines to identify synthetic-lethal interactions between cancer genomes and targeted gene deletions.  These results will be used to identify novel drug targets whose inhibition is lethal to cancer cells with specific molecular alterations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003348","title":"R_D__Genome_wide_CRISPR_Cas9_screening_of_Human_Organoid_Lines","description":"The study will perform genome-wide loss-of-function CRISPR-Cas9 screens across genetically annotated human organoid lines to idenify sythetic-lethal interaction between cancer genomes and targeted gene deletions.\n\n*Sequencing is performed on PCR products from the amplification of gRNA segments introduced into commercial cell lines. Cellular DNA or RNA are not sequenced. This data is defined as \"Other Biological/Biochemical Assay Data\" under the WTSI datasharing guidelines and consequently will be released at the time of publication and/or through faculty websites.","abstract":"The goal of this project is to perform genome-wide loss-of-function CRISPR-Cas9 screens across genetically annotated human organoid lines to identify synthetic-lethal interactions between cancer genomes and targeted gene deletions.  These results will be used to identify novel drug targets whose inhibition is lethal to cancer cells with specific molecular alterations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003349","title":"WTCCC2 Pre-eclampsia Study","description":"A WTCCC2 project genome-wide association study for pre-eclampsia (PA) in 4375 individuals from Colombia, genotyped on the Affymetrix 6.0 array.","abstract":"A WTCCC2 project genome-wide association study for pre-eclampsia (PA) in 4375 individuals from Colombia, genotyped on the Affymetrix 6.0 array.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-28T17:28:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003350","title":"ALPI deficiency causes refractory Inflammation Bowel Disease","description":"Herein, we report the first identification of biallelic-inherited mutations in ALPI as a Mendelian cause of inflammatory bowel disease in two unrelated patients. ALPI encodes for intestinal phosphatase alkaline, a brush border metalloenzyme that hydrolyses phosphate from the lipid A moiety of lipopolysaccharides and thereby drastically reduces Toll-like receptor 4 agonist activity. Prediction tools and structural modelling indicate that all mutations affect critical residues or inter-subunit interactions, and heterologous expression in HEK293T cells demonstrated that all ALPI mutations were loss of function. ALPI mutations impaired either stability or catalytic activity of ALPI and rendered it unable to detoxify lipopolysaccharide-dependent signalling. Furthermore, ALPI expression was reduced in patients' biopsies, and ALPI activity was undetectable in ALPI-deficient patient's stool. Our findings highlight the crucial role of ALPI in regulating host-microbiota interactions and restraining host inflammatory responses. These results indicate that ALPI mutations should be included in screening for monogenic causes of inflammatory bowel diseases and lay the groundwork for ALPI-based treatments in intestinal inflammatory disorders.","abstract":"Herein, we report the first identification of biallelic-inherited mutations in ALPI as a Mendelian cause of inflammatory bowel disease in two unrelated patients. ALPI encodes for intestinal phosphatase alkaline, a brush border metalloenzyme that hydrolyses phosphate from the lipid A moiety of lipopolysaccharides and thereby drastically reduces Toll-like receptor 4 agonist activity. Prediction tools and structural modelling indicate that all mutations affect critical residues or inter-subunit interactions, and heterologous expression in HEK293T cells demonstrated that all ALPI mutations were loss of function. ALPI mutations impaired either stability or catalytic activity of ALPI and rendered it unable to detoxify lipopolysaccharide-dependent signalling. Furthermore, ALPI expression was reduced in patients' biopsies, and ALPI activity was undetectable in ALPI-deficient patient's stool. Our findings highlight the crucial role of ALPI in regulating host-microbiota interactions and restraining host inflammatory responses. These results indicate that ALPI mutations should be included in screening for monogenic causes of inflammatory bowel diseases and lay the groundwork for ALPI-based treatments in intestinal inflammatory disorders.","study_type":"Other","pubmed_ids":[29567797],"external_links":null,"is_released":true,"released_date":"2018-11-28T19:56:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003351","title":"Circulating tumour DNA abundance and potential utility in de novo metastatic prostate cancer","description":"Several systemic therapeutic options exist for metastatic castration sensitive prostate cancer (mCSPC). Circulating tumour DNA can profile metastatic castration resistant prostate cancer and influence treatment decisions, but remains untested in mCSPC. We set out to determine ctDNA abundance at de novo mCSPC diagnosis and whether ctDNA provides complementary clinically relevant information to a prostate biopsy. We collected and sequenced 77 plasma cell-free DNA samples from 53 newly diagnosed patients with mCSPC. Targeted sequencing was also performed on DNA from 48 diagnostic prostate tissue samples.","abstract":"Several systemic therapeutic options exist for metastatic castration sensitive prostate cancer (mCSPC). Circulating tumour DNA can profile metastatic castration resistant prostate cancer and influence treatment decisions, but remains untested in mCSPC. We set out to determine ctDNA abundance at de novo mCSPC diagnosis and whether ctDNA provides complementary clinically relevant information to a prostate biopsy. We collected and sequenced 77 plasma cell-free DNA samples from 53 newly diagnosed patients with mCSPC. Targeted sequencing was also performed on DNA from 48 diagnostic prostate tissue samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-29T11:13:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003352","title":"Evaluation of commercial Guardant360 ctDNA test in metastatic prostate cancer","description":"Circulating tumor DNA (ctDNA) sequencing provides a minimally-invasive method for tumor molecular stratification. We compared the commercial Guardant360 ctDNA test to an academic sequencing approach for profiling of metastatic prostate cancer. Plasma cell-free DNA (cfDNA) from 24 patients was sequenced with a validated, prostate cancer specific targeted research panel, and sent for simultaneous Guardant360 analysis.","abstract":"Circulating tumor DNA (ctDNA) sequencing provides a minimally-invasive method for tumor molecular stratification. We compared the commercial Guardant360 ctDNA test to an academic sequencing approach for profiling of metastatic prostate cancer. Plasma cell-free DNA (cfDNA) from 24 patients was sequenced with a validated, prostate cancer specific targeted research panel, and sent for simultaneous Guardant360 analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-29T12:48:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003353","title":"Non-coding RNAs in breast cancer","description":"Using RNA CaptureSeq we annotated non-coding RNAs transcribed from genome intervals surrounding breast cancer risk signals in a range of mammary-derived tissue and cell lines.","abstract":"Using RNA CaptureSeq we annotated non-coding RNAs transcribed from genome intervals surrounding breast cancer risk signals in a range of mammary-derived tissue and cell lines.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-29T23:30:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003354","title":"Neoadjuvant chemotherapy alters the genomic landscape and immune  microenvironment of breast cancers","description":"To characterize the effects of neoadjuvant chemotherapy (NAC) on the genome, transcriptome and tumor infiltrating leukocytes (TILs), we have conducted whole exome and whole transcriptome sequencing of a comprehensive, longitudinal breast cancer cohort consisting of 146 cases and 281 paired tumor samples. In total, 52 (38%) patients achieved pathologic complete response (pCR) while 85 patients (62%) had\nresidual disease with standard chemotherapy regimen. Tumor biopsies were collected for each patient at three time points – pre-treatment, three weeks after the first cycle of anthracycline and cyclophosphamide (AC) and at the time of surgery after 3 more cycles of AC followed by 4 cycles of taxane or taxane plus Herceptin in case of HER2+ subtype.","abstract":"To characterize the effects of neoadjuvant chemotherapy (NAC) on the genome, transcriptome and tumor infiltrating leukocytes (TILs), we have conducted whole exome and whole transcriptome sequencing of a comprehensive, longitudinal breast cancer cohort consisting of 146 cases and 281 paired tumor samples. In total, 52 (38%) patients achieved pathologic complete response (pCR) while 85 patients (62%) had\nresidual disease with standard chemotherapy regimen. Tumor biopsies were collected for each patient at three time points – pre-treatment, three weeks after the first cycle of anthracycline and cyclophosphamide (AC) and at the time of surgery after 3 more cycles of AC followed by 4 cycles of taxane or taxane plus Herceptin in case of HER2+ subtype.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-30T00:20:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003355","title":"Gene expression in CSF and blood of patients with pneumococcal meningitis","description":null,"abstract":"Improving outcomes from pneumococcal meningitis (PM), particularly in populations with high HIV prevalence, requires better understanding of host inflammatory responses to infection. We compared the transcriptome in pre-antibiotic cerebrospinal fluid (CSF) and blood from Malawian adults with PM using RNA sequencing to identify associations with outcome.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-11-30T09:21:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003356","title":"Pilot_analysis_of_clone_specific_expression_in_blood_and_CSF","description":"In this pilot experiment we will analyse Peripheral Blood Mononuclear Cells (PBMCs) and Cerebro Spinal Fluid (CSF) cells  from 5 cases and 5 controls using the 5’ 10X sequencing library preparation and sequencing protocol. Participants will necessarily have to be recruited on different days owing to logistical and availability constraints. Due to the scarcity of live cells in the CSF we have ruled out freezing and resuscitating samples at a posterior time. Therefore, PBMCs and CSF will be processed on a donor to donor basis, and PBMCs will be stained with a hashing antibody against an ubiquitous antigen coupled to a barcoded oligo. CSF and hashed PBMCs from the same donor will be pooled (proposed ratio, 1:1) and loaded in the same 10X Chromium run to analyse a total of 4,000 cells per donor (ideally 2,000 PBMCs and 2,000 cells from the CSF). This pilot experiment will give us first pass level data regarding the extent to which cell type specific differences in expression in MS are clonally determined. Given that clonal expansion of T and B cells is a characteristic feature of the disease, this experiment is a logical next step and will allow us to establish the best way to expand the analysis to larger numbers of subjects and cells.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"In this pilot experiment we will analyse Peripheral Blood Mononuclear Cells (PBMCs) and Cerebro Spinal Fluid (CSF) cells  from 5 cases and 5 controls using the 5’ 10X sequencing library preparation and sequencing protocol. Participants will necessarily have to be recruited on different days owing to logistical and availability constraints. Due to the scarcity of live cells in the CSF we have ruled out freezing and resuscitating samples at a posterior time. Therefore, PBMCs and CSF will be processed on a donor to donor basis, and PBMCs will be stained with a hashing antibody against an ubiquitous antigen coupled to a barcoded oligo. CSF and hashed PBMCs from the same donor will be pooled (proposed ratio, 1:1) and loaded in the same 10X Chromium run to analyse a total of 4,000 cells per donor (ideally 2,000 PBMCs and 2,000 cells from the CSF). This pilot experiment will give us first pass level data regarding the extent to which cell type specific differences in expression in MS are clonally determined. Given that clonal expansion of T and B cells is a characteristic feature of the disease, this experiment is a logical next step and will allow us to establish the best way to expand the analysis to larger numbers of subjects and cells.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003357","title":"Genomic Profiling of Thyroid Cancer Reveals a Role for Thyroglobulin in Metastasis -Part II","description":"Papillary thyroid carcinoma (PTC) has a wide geographic variation in incidence, being highest in Saudi Arabia where it is only second to breast cancer as the most common cancer among females.  Genomic profiling of PTC from Saudi Arabia has not been attempted previously.  We performed whole-exome sequencing of 101 PTC samples and the corresponding genomic DNA to identify genes with recurrent somatic mutations, followed by sequencing of these genes using a next-generation gene panel approach in further 785 samples.  In addition to BRAF, N-RAS and H-RAS, which have previously been shown to be recurrently mutated in PTC, our analysis highlights additional genes, including thyroglobulin (TG), which harbored somatic mutations in 3% of the entire cohort.  Surprisingly, although TG mutations were not exclusive to mutations in the RAS-MAP kinase pathway, their presence was associated with a significantly worse clinical outcome, which suggests a pathogenic role beyond driving initial oncogenesis.  Analysis of metastatic PTC tissue revealed significant enrichment for TG mutations (p&lt;0.001), including events of apparent clonal expansion.  Our results suggest a previously unknown role of TG somatic mutations in the pathogenesis of PTC and its malignant evolution.","abstract":"Papillary thyroid carcinoma (PTC) has a wide geographic variation in incidence, being highest in Saudi Arabia where it is only second to breast cancer as the most common cancer among females.  Genomic profiling of PTC from Saudi Arabia has not been attempted previously.  We performed whole-exome sequencing of 101 PTC samples and the corresponding genomic DNA to identify genes with recurrent somatic mutations, followed by sequencing of these genes using a next-generation gene panel approach in further 785 samples.  In addition to BRAF, N-RAS and H-RAS, which have previously been shown to be recurrently mutated in PTC, our analysis highlights additional genes, including thyroglobulin (TG), which harbored somatic mutations in 3% of the entire cohort.  Surprisingly, although TG mutations were not exclusive to mutations in the RAS-MAP kinase pathway, their presence was associated with a significantly worse clinical outcome, which suggests a pathogenic role beyond driving initial oncogenesis.  Analysis of metastatic PTC tissue revealed significant enrichment for TG mutations (p&lt;0.001), including events of apparent clonal expansion.  Our results suggest a previously unknown role of TG somatic mutations in the pathogenesis of PTC and its malignant evolution.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-02T07:01:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003358","title":"Small intestinal neuroendocrine tumors","description":"The goal of this study was to gain insights into the transcriptomes, mutations and copy number variants present in small intestinal neuroendocrine tumors. The present dataset contains RNA-sequencing performed on seven such tumors.","abstract":"The goal of this study was to gain insights into the transcriptomes, mutations and copy number variants present in small intestinal neuroendocrine tumors. The present dataset contains RNA-sequencing performed on seven such tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-02T20:18:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003359","title":"Ancient nuclear genomes enable repatriation of Indigenous human remains","description":"For many decades Indigenous people, including Native Americans and Aboriginal Australians, have fought for their return of their ancient people.  By sequencing ten ancient nuclear genomes of Aboriginal Australians and 27 mitogenomes from ancient pre-European Aboriginal Australians (up to 1,540 yr BP) of known provenance we demonstrate the feasibility of successfully identifying the geographic origins of unprovenanced ancestral remains using genomic methods.","abstract":"For many decades Indigenous people, including Native Americans and Aboriginal Australians, have fought for their return of their ancient people.  By sequencing ten ancient nuclear genomes of Aboriginal Australians and 27 mitogenomes from ancient pre-European Aboriginal Australians (up to 1,540 yr BP) of known provenance we demonstrate the feasibility of successfully identifying the geographic origins of unprovenanced ancestral remains using genomic methods.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-02T23:01:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003360","title":"organoid data of colorectal cancers","description":null,"abstract":"todo","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-03T16:32:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003361","title":"Forty-Five patient-derived xenografts capture the clinical and biological heterogeneity of Wilms tumor","description":"The lack of model systems has limited the preclinical testing of novel therapies for Wilms tumor (WT) patients who have poor outcomes. Herein, we established 45 heterotopic WT patient-derived xenografts (WTPDX) in CB17 scid-/- mice that capture the biological heterogeneity of Wilms tumor (WT). These WTPDX include 6 from patients with diffuse anaplasia, 9 from patients who later experienced disease relapse, and 13 from patients with bilateral disease. Early passage WTPDX showed enrichment of blastemal gene expression. Favorable histology WTPDX were chemosensitive, whereas unfavorable histology WTPDX were resistant to conventional chemotherapy with vincristine, actinomycin-D, and doxorubicin given singly or in combination. This WTPDX library is a unique scientific resource that retains the spectrum of biological heterogeneity present in WT and provides an essential tool to test novel targeted therapies in the era of precision medicine.","abstract":"The lack of model systems has limited the preclinical testing of novel therapies for Wilms tumor (WT) patients who have poor outcomes. Herein, we established 45 heterotopic WT patient-derived xenografts (WTPDX) in CB17 scid-/- mice that capture the biological heterogeneity of Wilms tumor (WT). These WTPDX include 6 from patients with diffuse anaplasia, 9 from patients who later experienced disease relapse, and 13 from patients with bilateral disease. Early passage WTPDX showed enrichment of blastemal gene expression. Favorable histology WTPDX were chemosensitive, whereas unfavorable histology WTPDX were resistant to conventional chemotherapy with vincristine, actinomycin-D, and doxorubicin given singly or in combination. This WTPDX library is a unique scientific resource that retains the spectrum of biological heterogeneity present in WT and provides an essential tool to test novel targeted therapies in the era of precision medicine.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-03T17:10:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003362","title":"Uveal melanoma patient with germline MBD4 nonsense mutation","description":"There is currently no effective treatment for metastasised uveal melanoma (UM). Recently, it was reported that a UM patient was responsive to checkpoint inhibitor (CI) treatment, due to a high tumour mutation burden correlated with a germline loss-of-function MBD4 mutation. Here, we report on another UM patient who carried an MBD4 germline nonsense variant (p.Leu563Ter) and her tumour showed a 5-fold higher than average mutation burden. We confirmed the association between germline loss-of-function variant in MBD4 and CI response. The patient experienced stable disease (10 months) and survived two years with metastatic disease, which is twice as long as median survival. Additionally, the frequency of MBD4 loss-of-function variants in reported UM cohorts was &gt;20 times higher than in an aggregated population genome database (P &lt; 5x10-5), implying a potential role as UM predisposition gene. These findings provide a strong basis for the inclusion of MBD4 in screening of potential UM-prone families as well as stratification of immunotherapy.","abstract":"There is currently no effective treatment for metastasised uveal melanoma (UM). Recently, it was reported that a UM patient was responsive to checkpoint inhibitor (CI) treatment, due to a high tumour mutation burden correlated with a germline loss-of-function MBD4 mutation. Here, we report on another UM patient who carried an MBD4 germline nonsense variant (p.Leu563Ter) and her tumour showed a 5-fold higher than average mutation burden. We confirmed the association between germline loss-of-function variant in MBD4 and CI response. The patient experienced stable disease (10 months) and survived two years with metastatic disease, which is twice as long as median survival. Additionally, the frequency of MBD4 loss-of-function variants in reported UM cohorts was &gt;20 times higher than in an aggregated population genome database (P &lt; 5x10-5), implying a potential role as UM predisposition gene. These findings provide a strong basis for the inclusion of MBD4 in screening of potential UM-prone families as well as stratification of immunotherapy.","study_type":"Other","pubmed_ids":[30714079],"external_links":null,"is_released":true,"released_date":"2018-12-04T05:39:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003363","title":"Single-cell RNA-seq of immune cells sorted from human melanoma tumors","description":"Tumor immune cell compositions play a major role in response to immunotherapy but the heterogeneity and dynamics of immune infiltrates in human cancer lesions remain poorly characterized. Here we identify conserved intratumoral CD4 and CD8 T cell behaviors in  scRNA-seq data from 25 melanoma patients. We discover a large population of CD8 T cells showing continuous progression from an early effector \"transitional\" into a dysfunctional T cell state. CD8 T cells that express a complete cytotoxic gene set are rare, and TCR sharing data suggest their independence from the transitional and dysfunctional cell states. Notably, we demonstrate that dysfunctional T cells are the major intratumoral proliferating immune cell compartment and that the intensity of the dysfunctional signature is associated with tumor-reactivity. Our data demonstrate that CD8 T cells previously defined as exhausted, are in fact a highly proliferating, clonal and dynamically differentiating cell population within the human tumor microenvironment.","abstract":"Tumor immune cell compositions play a major role in response to immunotherapy but the heterogeneity and dynamics of immune infiltrates in human cancer lesions remain poorly characterized. Here we identify conserved intratumoral CD4 and CD8 T cell behaviors in  scRNA-seq data from 25 melanoma patients. We discover a large population of CD8 T cells showing continuous progression from an early effector \"transitional\" into a dysfunctional T cell state. CD8 T cells that express a complete cytotoxic gene set are rare, and TCR sharing data suggest their independence from the transitional and dysfunctional cell states. Notably, we demonstrate that dysfunctional T cells are the major intratumoral proliferating immune cell compartment and that the intensity of the dysfunctional signature is associated with tumor-reactivity. Our data demonstrate that CD8 T cells previously defined as exhausted, are in fact a highly proliferating, clonal and dynamically differentiating cell population within the human tumor microenvironment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-04T08:16:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003364","title":"Test study - testing upload","description":"This is a test study","abstract":"This is a test study","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003365","title":"Finding structural variation from the patient-derived xenografts of pediatric T-cell leukemia at the single-cell level","description":"In this study, we aimed to identify somatic structural variation of T-cell acute lymphoblastic leukemias (T-ALLs_ from patient-derived xenografts (PDX) at the single-cell level. For this purpose, we performed strand-specific single-cell sequencing of PDX-derived T-ALL relapse samples from two juvenile patients  (P1, P33). To validate structural variation detected via scTRIP, we profiled whole exome sequencing (WES) data from P33 (samples taken during initial disease, remission, relapse), and mate-pair sequencing data from P1 (relapse).","abstract":"In this study, we aimed to identify somatic structural variation of T-cell acute lymphoblastic leukemias (T-ALLs_ from patient-derived xenografts (PDX) at the single-cell level. For this purpose, we performed strand-specific single-cell sequencing of PDX-derived T-ALL relapse samples from two juvenile patients  (P1, P33). To validate structural variation detected via scTRIP, we profiled whole exome sequencing (WES) data from P33 (samples taken during initial disease, remission, relapse), and mate-pair sequencing data from P1 (relapse).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-05T23:48:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003366","title":"Microsatellite unstable colorectal cancers","description":"Immune escape has been recognised as one of the hallmarks of cancer. Overcoming this immunomodulatory process by tumour cells has become a major therapeutic target. Here we utilize organoid technology to study immune-cancer interactions and assess immunomodulation by colorectal cancer (CRC). Transcriptional profiling and flow cytometry revealed that organoids maintain differential expression of immunomodulatory molecules present in primary tumours. Finally, we established a method to model antigen-specific epithelial cell killing and cancer immunomodulation in vitro using CRC organoids co-cultured with cytotoxic T cells. Our method may serve as a first step to rebuilding the tumor microenvironment in vitro.","abstract":"Immune escape has been recognised as one of the hallmarks of cancer. Overcoming this immunomodulatory process by tumour cells has become a major therapeutic target. Here we utilize organoid technology to study immune-cancer interactions and assess immunomodulation by colorectal cancer (CRC). Transcriptional profiling and flow cytometry revealed that organoids maintain differential expression of immunomodulatory molecules present in primary tumours. Finally, we established a method to model antigen-specific epithelial cell killing and cancer immunomodulation in vitro using CRC organoids co-cultured with cytotoxic T cells. Our method may serve as a first step to rebuilding the tumor microenvironment in vitro.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-06T12:10:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003367","title":"Genomic and transcriptomic determinants of therapy resistance and immune landscape evolution during anti-EGFR treatment in colorectal cancer","description":"Despite biomarker stratification, the anti-EGFR antibody cetuximab is only effective against a subgroup of colorectal cancers (CRC). This genomic and transcriptomic analysis of the cetuximab resistance landscape in 35 RAS wild-type CRCs identified associations of NF-1 and non-canonical RAS/RAF-aberrations with primary resistance and validated transcriptomic CRC-subtypes as non-genetic predictors of benefit. 64% of biopsies with acquired resistance harbored no genetic resistance drivers. Most of these had switched from a cetuximab-sensitive transcriptomic subtype pre-treatment to a fibroblast- and growth factor-rich subtype at progression. Fibroblast-supernatant conferred cetuximab resistance in vitro, confirming a major role for non-genetic resistance through stromal remodeling. Cetuximab treatment increased cytotoxic immune infiltrates and PDL1 and LAG3 immune-checkpoint expression, potentially providing opportunities to treat cetuximab-resistant CRCs with immunotherapy.","abstract":"Despite biomarker stratification, the anti-EGFR antibody cetuximab is only effective against a subgroup of colorectal cancers (CRC). This genomic and transcriptomic analysis of the cetuximab resistance landscape in 35 RAS wild-type CRCs identified associations of NF-1 and non-canonical RAS/RAF-aberrations with primary resistance and validated transcriptomic CRC-subtypes as non-genetic predictors of benefit. 64% of biopsies with acquired resistance harbored no genetic resistance drivers. Most of these had switched from a cetuximab-sensitive transcriptomic subtype pre-treatment to a fibroblast- and growth factor-rich subtype at progression. Fibroblast-supernatant conferred cetuximab resistance in vitro, confirming a major role for non-genetic resistance through stromal remodeling. Cetuximab treatment increased cytotoxic immune infiltrates and PDL1 and LAG3 immune-checkpoint expression, potentially providing opportunities to treat cetuximab-resistant CRCs with immunotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-06T14:19:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003368","title":"Single-cell atlas of the developing brain to investigate the cellular origins of pediatric brain tumors","description":null,"abstract":"Gene expression is finely regulated during development, and deregulation can lead to disease. In pediatric brain tumors (PBT), disruption of neurodevelopmental gene regulation programs are suspected to drive oncogenesis. However, the transcriptional landscape and genetic regulation processes of the healthy developing brain are not fully characterized, limiting our investigation of these tumors. We used single-cell RNA-sequencing to generate a transcriptomic atlas of the developing forebrain and pons in human and mouse, two regions where PBT commonly arise. We projected bulk RNA-seq profiles for a cohort of 200 PBT onto these cell types, followed by focused analysis of three PBT subtypes by single-cell profiling: WNT medulloblastoma, embryonal tumors with multilayered rosettes (ETMR), and atypical teratoid/rhabdoid tumors (ATRT). In diffuse intrinsic pontine glioma (DIPG), we investigated the effect of removal of the driver H3K27M mutation on differentiation potential using primary tumor-derived cell lines. Altogether, for WNT medulloblastoma, ETMR, and DIPG, we pinpoint stalled differentiation during developmental programs as a common etiological mechanism of these tumors, providing a valuable resource to aid modeling and therapeutics.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-06T14:52:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003369","title":"Pancreatic cancer organoids recapitulate disease and allow personalized drug screening","description":"We report derivation of 30 Patient-Derived Organoid lines (PDOs) from tumors arising in the pancreas and distal bile duct. PDOs recapitulate tumor histology and contain genetic alterations typical for pancreatic cancer. In vitro testing of a panel of 76 therapeutic agents revealed sensitivities currently not exploited in the clinic. The PRMT5 inhibitor EZP015556, shown to target MTAP negative tumors, was validated as such, but also appeared to constitute an effective therapy for a subset of MTAP+ tumors. Taken together, the work presented here provides a platform to identify novel therapeutics to target pancreatic tumor cells using PDOs.","abstract":"We report derivation of 30 Patient-Derived Organoid lines (PDOs) from tumors arising in the pancreas and distal bile duct. PDOs recapitulate tumor histology and contain genetic alterations typical for pancreatic cancer. In vitro testing of a panel of 76 therapeutic agents revealed sensitivities currently not exploited in the clinic. The PRMT5 inhibitor EZP015556, shown to target MTAP negative tumors, was validated as such, but also appeared to constitute an effective therapy for a subset of MTAP+ tumors. Taken together, the work presented here provides a platform to identify novel therapeutics to target pancreatic tumor cells using PDOs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-07T12:48:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003370","title":"Mutational Patterns in Metastatic Cutaneous Squamous Cell Carcinoma","description":"Cutaneous squamous cell carcinoma (cSCC) from the head and neck typically metastasizes to the lymph nodes of the neck and parotid glands. When a primary is not identified, they are difficult to distinguish from metastases of mucosal origin and primary salivary gland SCC. Ultraviolet radiation causes a mutation pattern that predominantly features cytosine to thymine transitions at dipyrimidine sites and has been associated with cSCC. In this study, we used whole genome sequencing data from 15 cSCC metastases and show that a UV signature mutation is pervasive across the cohort and distinct from mucosal SCC. The mutational burden was exceptionally high and concentrated in some regions of the genome, especially insulator elements (mean 162 mutations / Mb). We therefore evaluated the likely impact of UV-induced mutations on the dipyrimidine rich binding site of the main human insulator protein, CCCTC-binding factor (CTCF), and the possible implications on CTCF function and the spatial organization of the genome. Our findings suggest that mutation signature analysis may be useful in determining the origin of metastases in the neck and the parotid gland. Furthermore, UV-induced DNA damage to insulator binding sites may play a role in the carcinogenesis and progression of cSCC.","abstract":"Cutaneous squamous cell carcinoma (cSCC) from the head and neck typically metastasizes to the lymph nodes of the neck and parotid glands. When a primary is not identified, they are difficult to distinguish from metastases of mucosal origin and primary salivary gland SCC. Ultraviolet radiation causes a mutation pattern that predominantly features cytosine to thymine transitions at dipyrimidine sites and has been associated with cSCC. In this study, we used whole genome sequencing data from 15 cSCC metastases and show that a UV signature mutation is pervasive across the cohort and distinct from mucosal SCC. The mutational burden was exceptionally high and concentrated in some regions of the genome, especially insulator elements (mean 162 mutations / Mb). We therefore evaluated the likely impact of UV-induced mutations on the dipyrimidine rich binding site of the main human insulator protein, CCCTC-binding factor (CTCF), and the possible implications on CTCF function and the spatial organization of the genome. Our findings suggest that mutation signature analysis may be useful in determining the origin of metastases in the neck and the parotid gland. Furthermore, UV-induced DNA damage to insulator binding sites may play a role in the carcinogenesis and progression of cSCC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-10T01:56:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003371","title":"Genomic characterization of esophageal squamous cell carcinoma reveals critical genes underlying tumorigenesis and poor prognosis","description":"The genetic mechanisms underlying the poor prognosis of esophageal squamous cell carcinoma (ESCC) are not well understood. In this study, we comprehensively characterized somatic mutations, copy number alterations (SCNAs)/structural variants (SVs) found in ESCC from sequencing 10 whole-genome and 57 whole-exome matched tumor-normal pairs. We identified multiple somatic mutations seen previously in known cancer pathways and identified candidate genes for ESCC including VANGL1 and MIR4707. A survival analysis based on the expression profiles of 321 ESCC individuals indicated that the somatically altered genes we found were significantly associated with ESCC poorer survival. Subsequently, we performed functional studies to validate the roles of the altered genes in tumor proliferation and metastasis.","abstract":"The genetic mechanisms underlying the poor prognosis of esophageal squamous cell carcinoma (ESCC) are not well understood. In this study, we comprehensively characterized somatic mutations, copy number alterations (SCNAs)/structural variants (SVs) found in ESCC from sequencing 10 whole-genome and 57 whole-exome matched tumor-normal pairs. We identified multiple somatic mutations seen previously in known cancer pathways and identified candidate genes for ESCC including VANGL1 and MIR4707. A survival analysis based on the expression profiles of 321 ESCC individuals indicated that the somatically altered genes we found were significantly associated with ESCC poorer survival. Subsequently, we performed functional studies to validate the roles of the altered genes in tumor proliferation and metastasis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003372","title":"Summary statistics from genome-wide association study in glioma of 12,488 cases and 18,169 controls.","description":"Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,488 cases and 18,169 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 × 10-9, odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 × 10-10, OR = 1.24), 16p13.3 (rs2562152; P = 1.93 × 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 × 10-11, OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 × 10-10, OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 × 10-9, OR = 1.19), 1q44 (rs12076373; P = 2.63 × 10-10, OR = 1.23), 2q33.3 (rs7572263; P = 2.18 × 10-10, OR = 1.20), 3p14.1 (rs11706832; P = 7.66 × 10-9, OR = 1.15), 10q24.33 (rs11598018; P = 3.39 × 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 × 10-10, OR = 1.16), 14q12 (rs10131032; P = 5.07 × 10-11, OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 × 10-9, OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.","abstract":"Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,488 cases and 18,169 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 × 10-9, odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 × 10-10, OR = 1.24), 16p13.3 (rs2562152; P = 1.93 × 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 × 10-11, OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 × 10-10, OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 × 10-9, OR = 1.19), 1q44 (rs12076373; P = 2.63 × 10-10, OR = 1.23), 2q33.3 (rs7572263; P = 2.18 × 10-10, OR = 1.20), 3p14.1 (rs11706832; P = 7.66 × 10-9, OR = 1.15), 10q24.33 (rs11598018; P = 3.39 × 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 × 10-10, OR = 1.16), 14q12 (rs10131032; P = 5.07 × 10-11, OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 × 10-9, OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.","study_type":"Other","pubmed_ids":[28346443],"external_links":null,"is_released":true,"released_date":"2018-12-10T17:07:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003373","title":"German early-onset prostate cancer cohort of the Pan-Prostate Cancer Genome (PPCG) project","description":"Prostate cancer is the most frequent malignant tumor in males and the second most frequent cause of cancer-related death. Currently, in Germany, more than 60,000 prostate cancers are diagnosed every year. Although most of these patients are treated in a curative attempt, more than 10,000 German men die from prostate cancer annually. Owing to the demographic changes of our society, a further doubling of prostate cancer incidences during the next 20 years is expected. Prostate cancer is generally considered a tumor of elderly men. However, a fraction of prostate cancers are diagnosed at the age of 55 years or less. For several reasons, these “early onset prostate cancers” may represent a key entity for the understanding of prostate cancer biology. First, it is likely that early onset prostate cancers represent a distinct molecular subgroup of prostate cancer (PCa), potentially characterized by relatively small numbers of genetic changes, some of which may be particularly strong driver mutations for PCa development. Second, a fraction of prostate cancers in young individuals could represent classical prostate cancers that are detected at a very early stage and might therefore have accumulated molecular changes/mutations occurring that are most instrumental for prostate cancer early detection. Third, PCa with hereditary backgrounds are likely to accumulate in the age group below 55 years. A comparison with other sample sets (e.g. from other ICGC consortia), a systematic genomic analysis of young men with PCa could therefore lead to the detection of mechanisms for hereditary PCa. Fourth, a better understanding of these tumors is particularly relevant as finding optimal treatment regimens is most critical in young cancer patients. We are analyzing the entire genomic DNA sequences of at least 200 PCas (and matched non-tumorous DNA) of young men (≤ 55y), to at least 30 fold coverage, and integrate single-nucleotide variants and genomic structural variations with differential methylation, mRNA and miRNA expression data.Tissues were collected at the University Medical Center Hamburg-Eppendorf. Sequencing was performed at DKFZ and NCT (Heidelberg), EMBL (Heidelberg), and MPIMG (Berlin). Data management and bioinformatic data analyses is being conducted at DKFZ.","abstract":"Prostate cancer is the most frequent malignant tumor in males and the second most frequent cause of cancer-related death. Currently, in Germany, more than 60,000 prostate cancers are diagnosed every year. Although most of these patients are treated in a curative attempt, more than 10,000 German men die from prostate cancer annually. Owing to the demographic changes of our society, a further doubling of prostate cancer incidences during the next 20 years is expected. Prostate cancer is generally considered a tumor of elderly men. However, a fraction of prostate cancers are diagnosed at the age of 55 years or less. For several reasons, these “early onset prostate cancers” may represent a key entity for the understanding of prostate cancer biology. First, it is likely that early onset prostate cancers represent a distinct molecular subgroup of prostate cancer (PCa), potentially characterized by relatively small numbers of genetic changes, some of which may be particularly strong driver mutations for PCa development. Second, a fraction of prostate cancers in young individuals could represent classical prostate cancers that are detected at a very early stage and might therefore have accumulated molecular changes/mutations occurring that are most instrumental for prostate cancer early detection. Third, PCa with hereditary backgrounds are likely to accumulate in the age group below 55 years. A comparison with other sample sets (e.g. from other ICGC consortia), a systematic genomic analysis of young men with PCa could therefore lead to the detection of mechanisms for hereditary PCa. Fourth, a better understanding of these tumors is particularly relevant as finding optimal treatment regimens is most critical in young cancer patients. We are analyzing the entire genomic DNA sequences of at least 200 PCas (and matched non-tumorous DNA) of young men (≤ 55y), to at least 30 fold coverage, and integrate single-nucleotide variants and genomic structural variations with differential methylation, mRNA and miRNA expression data.Tissues were collected at the University Medical Center Hamburg-Eppendorf. Sequencing was performed at DKFZ and NCT (Heidelberg), EMBL (Heidelberg), and MPIMG (Berlin). Data management and bioinformatic data analyses is being conducted at DKFZ.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003374","title":"MGRB TODO","description":null,"abstract":"TODO MGRB abstract","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003375","title":"Functional_studies_of_candidate_malaria_protective_polymorphisms","description":"The spread of resistance to drugs and insecticides by Plasmodium falciparum parasites and their mosquito vectors are hampering current efforts to control and eliminate malaria. New approaches are therefore needed. In the past, malaria genetics studies exemplified by those describing the relationship between Duffy blood group negativity and natural resistance to P. vivax malaria, have played an important role in elucidating key aspects of the host-parasite biology, thereby informing potential therapeutic targets including vaccines. In a large multi-country genome-wide association study we recently identified a number of novel malaria-protective polymorphisms, most of which were found in or near to genes that are important for the normal function of red blood cells (RBCs). The mechanisms underlying the protective effects of these polymorphisms have yet to be understood. Through this study we aim to perform a range of functional experimental assays with a view to gaining a better understanding of the manner in which such polymorphisms affect the dynamics of the host-parasite interaction and prevent severe malaria episodes. Specifically, we will investigate the effects of human genetic variation on (i) RBC structure and function, (ii) P. falciparum invasion in vitro using donor RBCs in culture, (iii) in vitro correlates of severe malaria, and (iv) transcriptomic and proteomic profiles of RBCs across genotype groups. Our hope is that findings from this study might inform the development of new approaches to the control and treatment of malaria.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The main objective of this study is to investigate the mechanisms through which several human genetic polymorphisms confer protection against severe Plasmodium falciparum malaria. Through laboratory experimental studies of malaria including flow cytometry-based parasite invasion assays, transcriptomic and proteomic profiling of red blood cells (RBCs), we would like to understand the biological impact of the malaria-protective polymorphisms on the structure and function of RBCs, thereby elucidating the mechanisms through which these factors confer protection against malaria.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003376","title":"Oxaliplatin mutational signature","description":"we exposed MCF10A and HepG2 cells for 2 months to oxaliplatin. After exposure, cells were expanded and single-cell sorting (FACS) was performed to generate single cell clones. These clones were then expanded and DNA was isolated for whole-genome sequencing","abstract":"we exposed MCF10A and HepG2 cells for 2 months to oxaliplatin. After exposure, cells were expanded and single-cell sorting (FACS) was performed to generate single cell clones. These clones were then expanded and DNA was isolated for whole-genome sequencing","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003377","title":"Carboplatin mutational signature","description":"we exposed MCF10A and HepG2 cells for 2 months to carboplatin. After exposure, cells were expanded and single-cell sorting (FACS) was performed to generate single cell clones. These clones were then expanded and DNA was isolated for whole-genome sequencing","abstract":"we exposed MCF10A and HepG2 cells for 2 months to carboplatin. After exposure, cells were expanded and single-cell sorting (FACS) was performed to generate single cell clones. These clones were then expanded and DNA was isolated for whole-genome sequencing","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003378","title":"Doxorubicin mutational signature","description":"we exposed MCF10A and HepG2 cells for 2 months to doxorubicin. After exposure, cells were expanded and single-cell sorting (FACS) was performed to generate single cell clones. These clones were then expanded and DNA was isolated for whole-genome sequencing","abstract":"we exposed MCF10A and HepG2 cells for 2 months to doxorubicin. After exposure, cells were expanded and single-cell sorting (FACS) was performed to generate single cell clones. These clones were then expanded and DNA was isolated for whole-genome sequencing","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003379","title":"Somatic variations detected from whole genome sequencing data of bladder cancer","description":null,"abstract":"Bladder cancer is one of the most common and highly vascularized cancers. To better understand its genomic structure and underlying etiology, we conducted whole-genome and targeted sequencing in urothelial bladder carcinomas (UBCs, the most common type of bladder cancer). A greatly extended mutational landscape including both coding and noncoding regions was indentified.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003380","title":"PTPN22 SNPs and outcome after lung transplantation","description":"Obstructive chronic lung allograft dysfunction (BOS) is the major limiting factor for lung transplantation (LTx) outcome. PTPN22 is described as the hallmark autoimmunity gene, and one specific single nucleotide polymorphism (SNP), rs2476601, is associated with multiple autoimmune diseases, impaired T cell regulation and autoantibody formation. Taking into consideration the contribution of autoimmunity to LTx outcome, we hypothesized that polymorphisms in the PTPN22 gene could be associated with BOS incidence. We selected six SNPs within PTPN22 and analyzed both patient and donor genotypes on BOS development post-LTx. A total of 144 patients and matched donors were included, and individual SNPs and haplotype configurations were analyzed.","abstract":"Obstructive chronic lung allograft dysfunction (BOS) is the major limiting factor for lung transplantation (LTx) outcome. PTPN22 is described as the hallmark autoimmunity gene, and one specific single nucleotide polymorphism (SNP), rs2476601, is associated with multiple autoimmune diseases, impaired T cell regulation and autoantibody formation. Taking into consideration the contribution of autoimmunity to LTx outcome, we hypothesized that polymorphisms in the PTPN22 gene could be associated with BOS incidence. We selected six SNPs within PTPN22 and analyzed both patient and donor genotypes on BOS development post-LTx. A total of 144 patients and matched donors were included, and individual SNPs and haplotype configurations were analyzed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-12T11:29:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003381","title":"Collected tissue samples were digested using collagenase type II (Invitrogen, cat. #17101-015) and collagenase type IV (Invitrogen, cat. #17104-019) into single cell suspension. For all primary tumors and lymph nodes, non-immune cells, T cells and non-T-immune cells were separated using CD45 (APC anti-human CD45 Antibody, BioLegend, cat. #368512) and CD3 (FITC anti-human CD3 Antibody, BioLegend, cat. #300306) antibody by fluorescence-activated cell sorting (FACS). For normal tissues, CD45- non-immune cells were collected.","description":"We performed multi-omics sequencing of samples from 9 CRC patients and 2 normal people. Matched normal tissues (NT), primary tumors (PT), and lymph node metastases (LN) from CRC patients, and peripheral blood (NB) from normal people were collected. We identified the cell types of 1,520 immune cells which passed quality control based on the transcriptome data. These cells were clustered into 6 major groups (B cells, T cells, NK cells, macrophages, mast cells and undefined other immunes cells) according to known markers.","abstract":"We performed multi-omics sequencing of samples from 9 CRC patients and 2 normal people. Matched normal tissues (NT), primary tumors (PT), and lymph node metastases (LN) from CRC patients, and peripheral blood (NB) from normal people were collected. We identified the cell types of 1,520 immune cells which passed quality control based on the transcriptome data. These cells were clustered into 6 major groups (B cells, T cells, NK cells, macrophages, mast cells and undefined other immunes cells) according to known markers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003382","title":"Detection of mutational patterns in cell free DNA (cfDNA) of colorectal cancer by custom amplicon sequencing","description":"Monitoring the mutational patterns of solid tumors during cancer therapy is a major challenge in oncology. Analysis of mutations in cell free (cf) DNA offers a non-invasive approach to detect mutations that may be prognostic for disease survival or predictive for primary or secondary drug resistance. A main challenge for the application of cfDNA as a diagnostic tool is the diverse mutational landscape of cancer. Here, we developed a flexible end-to-end experimental and bioinformatics workflow to analyze mutations in cfDNA using custom amplicon sequencing. Our approach relies on open software tools to select primers suitable for multiplex PCR using minimal cfDNA as input. In addition, we developed a robust linear model to identify specific genetic alterations from sequencing data of cfDNA. We used our method to design a custom amplicon panel suitable for detection of hotspot mutations relevant for colorectal cancer and analyzed mutations in serial cfDNA samples from 34 patients with advanced colorectal cancer. Our data demonstrates that recurrent and patient-specific mutational patterns can be reliably detected for the majority of patients. Furthermore, we show that the allele frequency of mutations in cfDNA correlates well with disease progression. Finally, we demonstrate that monitoring of cfDNA can outperform the predictive power of currently used tumor markers and reveal mechanisms of resistance to anti-EGFR antibody treatment.","abstract":"Monitoring the mutational patterns of solid tumors during cancer therapy is a major challenge in oncology. Analysis of mutations in cell free (cf) DNA offers a non-invasive approach to detect mutations that may be prognostic for disease survival or predictive for primary or secondary drug resistance. A main challenge for the application of cfDNA as a diagnostic tool is the diverse mutational landscape of cancer. Here, we developed a flexible end-to-end experimental and bioinformatics workflow to analyze mutations in cfDNA using custom amplicon sequencing. Our approach relies on open software tools to select primers suitable for multiplex PCR using minimal cfDNA as input. In addition, we developed a robust linear model to identify specific genetic alterations from sequencing data of cfDNA. We used our method to design a custom amplicon panel suitable for detection of hotspot mutations relevant for colorectal cancer and analyzed mutations in serial cfDNA samples from 34 patients with advanced colorectal cancer. Our data demonstrates that recurrent and patient-specific mutational patterns can be reliably detected for the majority of patients. Furthermore, we show that the allele frequency of mutations in cfDNA correlates well with disease progression. Finally, we demonstrate that monitoring of cfDNA can outperform the predictive power of currently used tumor markers and reveal mechanisms of resistance to anti-EGFR antibody treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-12T15:03:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003383","title":"ProjectMinE :llumina HiSeqX and HiSeq 2000 whole genome sequence data on 3,001 ALS samples including 212 with known C9orf72 repeat expansions","description":"Whole genome sequence (WGS) data was generated on 3,001 samples previously quantified for the presence of the C9orf72 repeat expansion (212 expanded and 2,789 wild type), These samples were sequenced using a combination of 2x100bp reads on an Illumina HiSeq2000 and 2x150bp reads on an Illumina HiSeqX sequencer. The repeat expansions were called using ExpansionHunter to demonstrate the ability to call large repeats from high throughput, WGS data. Provided here are all read pairs where at least one of the reads aligns within 1kb of the C9orf72 repeat expansion in addition to reads aligned in pre-determined off target locations where the aligners are known to mis-align reads.","abstract":"Whole genome sequence (WGS) data was generated on 3,001 samples previously quantified for the presence of the C9orf72 repeat expansion (212 expanded and 2,789 wild type), These samples were sequenced using a combination of 2x100bp reads on an Illumina HiSeq2000 and 2x150bp reads on an Illumina HiSeqX sequencer. The repeat expansions were called using ExpansionHunter to demonstrate the ability to call large repeats from high throughput, WGS data. Provided here are all read pairs where at least one of the reads aligns within 1kb of the C9orf72 repeat expansion in addition to reads aligned in pre-determined off target locations where the aligners are known to mis-align reads.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-12T15:08:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003384","title":"Lymphocyte_LCM_WGS","description":"Using whole genome sequencing of lymphocytes excised from human tissue using laser capture microscopy (LCM), we identify the mutations arising in these microenvironments. This work will contribute towards developing a catalogue of mutations present in tissue resident lymphocytes across a range of tissues, and will characterize the mutational signatures that result from each microenvironment.","abstract":"As we age, our cells accumulate mutations, termed \"somatic mutations\". Somatic mutations, which exist in mosaic form throughout the body, are a direct record of the evolution of our cells. Some of these mutations are subject to neutral evolution. The study of neutral mutations can reveal the cell lineages resulting from normal development and tissue maintenance, and help us understand key demographic parameter of somatic evolution, such as population size and migration. Other mutations are under selection, resulting in the expansion or contraction of lineages. These mutations can lead to disease, such as cancer; however, the extent of selection on somatic mutations in not understood. We aim to understand the somatic evolution of the primary cells of the adaptive immune system, lymphocytes. As we age, lymphocytes accumulate somatic mutations, which reveal the evolutionary history of lymphocytes, as well as providing information about the particular mutations and lineage structures that contribute to age-related immune disorder. In order to understand somatic evolution in lymphocytes, we sequence lymphocytes from normal, healthy individuals across a range of ages. We perform whole-genome sequencing of LCM excised T and B cell colonies to identify somatic mutations, and perform targeted deep-sequencing of these mutations. The lineages of T and B cells, and the frequencies of these mutations reveals the neutral and non-neutral evolutionary processes underlying lymphocyte growth.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-12T16:27:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003385","title":"Whole genome sequencing of Ewings Sarcoma","description":"Sarcomas are cancers of the bone and soft tissue often defined by their gene fusions. However, the timing, context, and processes by which these pathogenic fusions arise are unknown. We explored this in Ewing sarcoma, a cancer driven by EWSR1-ETS fusions, with very few cooperating mutations. Combining whole-genome sequencing with enhanced informatics, we found that the EWSR1-ETS fusion arose from striking rearrangement clusters in 42% of cases (52/124). Notably, these were organized in loops that universally contained the fusion at their center, while also weaving up to 18 genes together with it. We found the same pattern of rearrangements in three additional types of sarcoma. From these data, we define a new signature for sarcoma fusions that precedes other somatic changes, in the earliest replicating DNA of the genome. This dramatic, sudden process impinges on many genes – generating\nmultiple coding changes that profoundly affect the transcriptome, with the disease-defining gene fusion at its core. These rearrangement loops emerge in an early ES clone from which both the primary tumor and the lethal relapse emerged, and then evolved in parallel until clinically detected.","abstract":"Sarcomas are cancers of the bone and soft tissue often defined by their gene fusions. However, the timing, context, and processes by which these pathogenic fusions arise are unknown. We explored this in Ewing sarcoma, a cancer driven by EWSR1-ETS fusions, with very few cooperating mutations. Combining whole-genome sequencing with enhanced informatics, we found that the EWSR1-ETS fusion arose from striking rearrangement clusters in 42% of cases (52/124). Notably, these were organized in loops that universally contained the fusion at their center, while also weaving up to 18 genes together with it. We found the same pattern of rearrangements in three additional types of sarcoma. From these data, we define a new signature for sarcoma fusions that precedes other somatic changes, in the earliest replicating DNA of the genome. This dramatic, sudden process impinges on many genes – generating\nmultiple coding changes that profoundly affect the transcriptome, with the disease-defining gene fusion at its core. These rearrangement loops emerge in an early ES clone from which both the primary tumor and the lethal relapse emerged, and then evolved in parallel until clinically detected.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-12T16:32:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003386","title":"Nuclear_single_seq_pilot","description":"The aim of this study is to analyse the genomes of tumours","abstract":"The aim of this study is to analyse the genomes of tumours","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-12T16:52:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003387","title":"Single cell RNA sequencing and Whole Genome Sequencing on different cells from the same sample for a triple negative patient derived xenograft and ovarian cancer cell lines.","description":"Measuring gene expression of genomically defined tumour clones at single cell resolution would associate functional consequences to somatic alterations, as a prelude to elucidating pathways driving cell population growth, resistance and relapse. In the absence of scalable methods to simultaneously assay DNA and RNA from the same single cell, independent sampling of cell populations for parallel measurement of single cell DNA and single cell RNA must be computationally mapped for genome-transcriptome association. Here we present clonealign, a robust statistical framework to assign gene expression states to cancer clones using single-cell RNA-seq and DNA-seq independently sampled from an heterogeneous cancer cell population. We apply clonealign to triple-negative breast cancer patient derived xenografts and high-grade serous ovarian cancer cell lines and discover clone-specific dysregulated biological pathways not visible using either DNA-Seq or RNA-Seq alone.","abstract":"Measuring gene expression of genomically defined tumour clones at single cell resolution would associate functional consequences to somatic alterations, as a prelude to elucidating pathways driving cell population growth, resistance and relapse. In the absence of scalable methods to simultaneously assay DNA and RNA from the same single cell, independent sampling of cell populations for parallel measurement of single cell DNA and single cell RNA must be computationally mapped for genome-transcriptome association. Here we present clonealign, a robust statistical framework to assign gene expression states to cancer clones using single-cell RNA-seq and DNA-seq independently sampled from an heterogeneous cancer cell population. We apply clonealign to triple-negative breast cancer patient derived xenografts and high-grade serous ovarian cancer cell lines and discover clone-specific dysregulated biological pathways not visible using either DNA-Seq or RNA-Seq alone.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-12T21:09:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003388","title":"Whole-genome sequencing identifies ADGRG6 enhancer mutations and FRS2 duplications as angiogenesis-related drivers in bladder cancer","description":"Bladder cancer is one of the most common and highly vascularized cancers. To better understand its genomic structure and underlying etiology, we conducted whole-genome sequencing in 65 urothelial bladder carcinomas (the most common type of bladder cancer) and identified recurrent genetic alterations in a set of angiogenesis genes, facilitating the understanding of molecular mechanisms underlying pathological angiogenesis in this type of cancer.","abstract":"Bladder cancer is one of the most common and highly vascularized cancers. To better understand its genomic structure and underlying etiology, we conducted whole-genome sequencing in 65 urothelial bladder carcinomas (the most common type of bladder cancer) and identified recurrent genetic alterations in a set of angiogenesis genes, facilitating the understanding of molecular mechanisms underlying pathological angiogenesis in this type of cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-13T00:54:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003389","title":"The Medical Genome Reference Bank: a whole genome data resource of 4,000 healthy elderly individuals.","description":null,"abstract":"Allele frequency data from human reference populations is of increasing value for filtering and assignment of pathogenicity to genetic variants. Aged and healthy populations are more likely to be selectively depleted of pathogenic alleles, and therefore particularly suitable as a reference populations for the major diseases of clinical and public health importance. However, reference studies of the healthy elderly have remained under represented in human genetics. We have developed the Medical Genome Reference Bank (MGRB), a large scale comprehensive whole genome dataset of confirmed healthy elderly individuals, to provide a publicly accessible resource for health related research, and for clinical genetics. It also represents a useful resource for studying the genetics of healthy aging. The MGRB comprises 4,000 healthy, older individuals with no reported history of cancer, cardiovascular disease or dementia, recruited from two Australian community based cohorts. DNA derived from blood samples will be subject to whole genome sequencing. The MGRB will measure genome wide genetic variation in 4,000 individuals, mostly of European decent, aged 60 to 95 years (mean age 75 years). The MGRB has committed to a policy of data sharing, employing a hierarchical data management system to maintain participant privacy and confidentiality, whilst maximizing research and clinical usage of the database. The MGRB will represent a dataset of international significance, broadly accessible to the clinical and genetic research community.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003390","title":"Microglial_phenotypes_in_stem_cell_derived_cortical_organoids","description":"Transcriptome analysis of different genotypes of stem cell-derived microglia in co-culture with cortical organoids. \nStem cell-derived microglial-like cells of different background (iPSC and ES) can be used to understand the interactions of neurons and the immune system in the context of neurodegeneration in vitro. Here, we use co-culture systems of stem cell-derived cortical organoids and microglia to uncover the transcriptional response to mutations causing familal Alzheimer's disease.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Transcriptome analysis of different genotypes of stem cell-derived microglia in co-culture with cortical organoids. \nStem cell-derived microglial-like cells of different background (iPSC and ES) can be used to understand the interactions of neurons and the immune system in the context of neurodegeneration in vitro. Here, we use co-culture systems of stem cell-derived cortical organoids and microglia to uncover the transcriptional response to mutations causing familal Alzheimer's disease.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003391","title":"MutWP6__CRUK_Grand_Challenge_Mutographs_of_Cancer__normal_","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nWithin Mutographs, work lead by the Sanger Institute will investigate whether detection of somatic mutations and mutational signatures in circulating white blood cells can be developed into a practical, generic system for surveying and monitoring multiple different endogenous and exogenous exposures, providing an ‘observatory’ on somatic mutational processes in humans.\n\nWhole genome sequences are generated at the Wellcome Sanger Institute (Illumina HiSeqX). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nWithin Mutographs, work lead by the Sanger Institute will investigate whether detection of somatic mutations and mutational signatures in circulating white blood cells can be developed into a practical, generic system for surveying and monitoring multiple different endogenous and exogenous exposures, providing an ‘observatory’ on somatic mutational processes in humans.\n\nWhole genome sequences are generated at the Wellcome Sanger Institute (Illumina HiSeqX). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003392","title":"Next Generation-Targeted Amplicon Sequencing (NG-TAS): An optimised protocol and computational pipeline for cost-effective profiling of circulating tumour DNA","description":"Circulating tumour DNA (ctDNA) detection and monitoring has enormous potential clinical utility in oncology. We describe here a fast, flexible and cost-effective method to profile multiple genes simultaneously in low input cell-free DNA (cfDNA): Next Generation-Targeted Amplicon Sequencing (NG-TAS). We designed a panel of 377 amplicons spanning 20 cancer genes and tested the NG-TAS pipeline using cell-free DNA from two hapmap lymphoblastoid cell lines. NG-TAS consistently detected mutations in cfDNA when mutation allele fraction was &gt;1%. We applied NG-TAS to a clinical cohort of metastatic breast cancer patients, demonstrating its potential in monitoring the disease. The computational pipeline is available at: https://github.com/cclab-brca/NGTAS_pipeline.","abstract":"Circulating tumour DNA (ctDNA) detection and monitoring has enormous potential clinical utility in oncology. We describe here a fast, flexible and cost-effective method to profile multiple genes simultaneously in low input cell-free DNA (cfDNA): Next Generation-Targeted Amplicon Sequencing (NG-TAS). We designed a panel of 377 amplicons spanning 20 cancer genes and tested the NG-TAS pipeline using cell-free DNA from two hapmap lymphoblastoid cell lines. NG-TAS consistently detected mutations in cfDNA when mutation allele fraction was &gt;1%. We applied NG-TAS to a clinical cohort of metastatic breast cancer patients, demonstrating its potential in monitoring the disease. The computational pipeline is available at: https://github.com/cclab-brca/NGTAS_pipeline.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003393","title":"5-Formylcytosine Landscapes of Human Preimplantation Embryos at Single-cell Resolution","description":"Epigenetic regulation is a crucial element for early embryo development, which promotes the key regulator expression to complete the reprogramming process. The dynamic of DNA methylation have been extensively studied in mouse and human early embryos during preimplantation development. In humans, the embryos go through two waves of active demethylation after fertilization. Active demethylation plays a key role in many biological process, such as early embryo development, primordial germ cell development and neuron differenciation. It is mediated by ten-eleven translocation protein family (TET) to produce a serial of oxidized derivatives of 5-methylcytosine (5mC), including 5-hydroxylmethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). The latter two can be further mediated by TDG passway to produce regular cytosine. The genome-wide 5-formylcytosine, the demethylation status, in human early embryos is largely unknown.","abstract":"Epigenetic regulation is a crucial element for early embryo development, which promotes the key regulator expression to complete the reprogramming process. The dynamic of DNA methylation have been extensively studied in mouse and human early embryos during preimplantation development. In humans, the embryos go through two waves of active demethylation after fertilization. Active demethylation plays a key role in many biological process, such as early embryo development, primordial germ cell development and neuron differenciation. It is mediated by ten-eleven translocation protein family (TET) to produce a serial of oxidized derivatives of 5-methylcytosine (5mC), including 5-hydroxylmethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). The latter two can be further mediated by TDG passway to produce regular cytosine. The genome-wide 5-formylcytosine, the demethylation status, in human early embryos is largely unknown.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003394","title":"Naive B-cell receptor heavy chain repertoire of celiac patients and healthy controls","description":null,"abstract":"We sequenced the naïve B-cell IGH repertoire of 100 individuals. Approximately half of the individuals enrolled in the study have celiac disease (n=52) and the others are controls (n=48).","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003395","title":"Naive B-cell receptor heavy chain repertoire of celiac patients and healthy controls","description":null,"abstract":"We sequenced the naïve B-cell IGH repertoire of 100 individuals. Approximately half of the individuals enrolled in the study have celiac disease (n=52) and the others are controls (n=48).","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003396","title":"Hepatocellular carcinoma xenografts established from needle biopsies preserve the characteristics of the originating tumors","description":null,"abstract":"Background &amp; Aims: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide with limited treatment options for patients with advanced stage disease. A major obstacle in preclinical drug development is the lack of an in vivo model that accurately reflects the broad spectrum of human HCC. Patient derived xenograft (PDX) mouse models could overcome the limitations of cancer cell lines. PDX models have been established from surgically resected HCCs. We aimed to establish and characterize PDX models from human HCC biopsies in order to expand the spectrum of HCC xenografts to advanced HCCs not amenable to surgery.\nMethods: Fifty-four human HCC needle biopsies were transplanted subcutaneously into immunodeficient NOD-SCID gamma-c (NSG) mice. Tumor growth rates, histopathological characteristics, RNA sequencing and whole exome sequencing were used to characterize the newly established mouse models and to compare them to the originating HCCs.\nResults: Eleven HCCs engrafted in NSG mice. They were derived from patients with various underlying liver diseases and tumor stages. All successfully transplanted HCCs were Edmondson grade III or IV. HCC PDX tumors retained the histopathological, transcriptomic and genomic characteristics of the original HCC biopsies over several generations of re-transplantation, including Edmondson grade, expression of tumor markers, tumor gene signature, tumor-associated mutations and copy number alterations.\nConclusion: PDX mouse models can be established from undifferentiated HCCs with an overall success rate of about 20%. The transplanted tumors represent the entire spectrum of the molecular landscape of HCCs and preserve the characteristics of the originating tumors. HCC PDX models are a promising tool for preclinical personalized drug development.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-17T13:14:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003397","title":"HSC_population_dynamics___CB001_samples","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-17T14:51:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003398","title":"do not use (deleted)","description":"deleted","abstract":"deleted","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003399","title":"Familial Myeloid Leukemia","description":"Exomes from 48 individuals affected by some form of familial myeloid leukemia (MDS, AML, BMF TCP) with variants in 60 candidate genes","abstract":"Exomes from 48 individuals affected by some form of familial myeloid leukemia (MDS, AML, BMF TCP) with variants in 60 candidate genes","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-17T23:03:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003400","title":"Whole-exome sequencing of NTHL1 deficient tumors","description":null,"abstract":"Biallelic germline mutations affecting NTHL1 predispose carriers to adenomatous polyposis and colorectal cancer, but the complete phenotype is unknown. We describe 29 individuals carrying biallelic germline NTHL1 mutations from 17 families, of which 26 developed one (n=10) or multiple (n=16) malignancies in 14 different tissues. An unexpected high breast cancer incidence was observed in female carriers (60%). Mutational signature analysis of 14 tumors from seven organs revealed that NTHL1 deficiency underlies the main mutational process in all but one of the tumors (93%). These results reveal NTHL1 as a multi-tumor predisposition gene with a high lifetime risk for extracolonic cancers and a typical mutational signature observed across tumor types, which can assist in the recognition of this syndrome.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-18T10:39:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003401","title":"Clonal_architecture_of_pre_malignant_and_malignant_tumours","description":"Single cells have been isolated from normal lung and pre-invasive lung cancer lesions from patients. These have been grown into colonies that will then be analysed for gene expression using RNA sequencing. Combined with previous whole-genome sequencing data, this will reveal the heterogeneity within cells and causative cell-intrinsic processes.","abstract":"Single cells have been isolated from normal lung and pre-invasive lung cancer lesions from patients. These have been grown into colonies that will then be analysed for gene expression using RNA sequencing. Combined with previous whole-genome sequencing data, this will reveal the heterogeneity within cells and causative cell-intrinsic processes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003402","title":"Pilot_study_of_the_interaction_between_phagocytosis_and_the_transcriptome_in_human_iPSC_derived_macropahges","description":"Pilot project analysing single-cell trascriptomes of human iPSC-dervied macrophages from phagocytosis assays.\nStem cell derived (iPSC) macrophages can be used in an in-vitro setting to model the functional role of the cell in health and disease. Here we are performing a pilot study to compare transcriptional responses of macrophages undergoing phagocytosis at the single-cell level.. . \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Pilot project analysing single-cell trascriptomes of human iPSC-dervied macrophages from phagocytosis assays.\nStem cell derived (iPSC) macrophages can be used in an in-vitro setting to model the functional role of the cell in health and disease. Here we are performing a pilot study to compare transcriptional responses of macrophages undergoing phagocytosis at the single-cell level.. . \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003403","title":"Studying_the_interaction_of_stem_cell_derived_microglia_and_neurons","description":"Transcriptome analysis of stem cell dervied microglia in a variety of in-vitro model systems \n\nStem cell derived (iPSC and ES cell) microglia-like cells can be used in an in-vitro setting to model the functional role of the cell in health and disease. Here we study the transcriptome differences of a variety of microglia model systems, including when cultured in the presence of neurons. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Transcriptome analysis of stem cell dervied microglia in a variety of in-vitro model systems \n\nStem cell derived (iPSC and ES cell) microglia-like cells can be used in an in-vitro setting to model the functional role of the cell in health and disease. Here we study the transcriptome differences of a variety of microglia model systems, including when cultured in the presence of neurons. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003404","title":"DECIPHER pooled shRNA library screen identifies PP2A  and FGFR signaling as potential therapeutic targets for DIPGs.","description":"Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive pediatric brain tumors that are characterized by a recurrent mutation (K27M) within the histone H3 encoding genes H3F3A or HIST1H3A/B/C. These mutations have been shown to induce a global reduction in the repressive histone modification H3K27me3, which together with widespread changes in DNA methylation patterns results in an extensive transcriptional reprogramming hampering the identification of single therapeutic targets based on a molecular rationale. We applied a large-scale gene knockdown approach using a pooled shRNA library in combination with next-generation sequencing in order to identify DIPG-specific vulnerabilities. The therapeutic potential of specific inhibitors of candidate targets was validated in a secondary drug screen. We identified fibroblast growth factor receptor (FGFR) signaling and the serine/threonine protein phosphatase 2A (PP2A) as top depleted hits in patient-derived DIPG cell cultures and validated their lethal potential by FGF ligand depletion and genetic knockdown of the PP2A structural subunit PPP2R1A. Further, pharmacological inhibition of FGFR and PP2A signaling through ponatinib and LB-100 treatment, respectively, exhibited strong tumor-specific anti-proliferative and apoptotic activity in cultured DIPG cells. Our findings suggest FGFR and PP2A signaling as potential new therapeutic targets for the treatment of DIPGs.","abstract":"Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive pediatric brain tumors that are characterized by a recurrent mutation (K27M) within the histone H3 encoding genes H3F3A or HIST1H3A/B/C. These mutations have been shown to induce a global reduction in the repressive histone modification H3K27me3, which together with widespread changes in DNA methylation patterns results in an extensive transcriptional reprogramming hampering the identification of single therapeutic targets based on a molecular rationale. We applied a large-scale gene knockdown approach using a pooled shRNA library in combination with next-generation sequencing in order to identify DIPG-specific vulnerabilities. The therapeutic potential of specific inhibitors of candidate targets was validated in a secondary drug screen. We identified fibroblast growth factor receptor (FGFR) signaling and the serine/threonine protein phosphatase 2A (PP2A) as top depleted hits in patient-derived DIPG cell cultures and validated their lethal potential by FGF ligand depletion and genetic knockdown of the PP2A structural subunit PPP2R1A. Further, pharmacological inhibition of FGFR and PP2A signaling through ponatinib and LB-100 treatment, respectively, exhibited strong tumor-specific anti-proliferative and apoptotic activity in cultured DIPG cells. Our findings suggest FGFR and PP2A signaling as potential new therapeutic targets for the treatment of DIPGs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003405","title":"KIT-dependent and -independent genomic heterogeneity of resistance in gastrointestinal stromal tumors - TORC1/2 inhibition as salvage strategy","description":"The mutational status of GIST analyzed with a broad sequencing approach (WES, RNAseq)","abstract":"The mutational status of GIST analyzed with a broad sequencing approach (WES, RNAseq)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-19T14:30:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003406","title":"Sequencing Study in COPD cases and controls","description":"Since smokers with COPD have a higher risk of developing lung cancer than those without, we hypothesized that they carry more mutations in affected tissue. We called somatic mutations in airway brush samples from medium-coverage whole genome sequencing data from healthy never and ex-smokers (n=8), as well as from ex-smokers with variable degrees of COPD (n=4). Owing to the limited concordance of resulting calls between the applied tools we built a consensus, a strategy that was validated with high accuracy for cancer data.","abstract":"Since smokers with COPD have a higher risk of developing lung cancer than those without, we hypothesized that they carry more mutations in affected tissue. We called somatic mutations in airway brush samples from medium-coverage whole genome sequencing data from healthy never and ex-smokers (n=8), as well as from ex-smokers with variable degrees of COPD (n=4). Owing to the limited concordance of resulting calls between the applied tools we built a consensus, a strategy that was validated with high accuracy for cancer data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-19T15:21:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003407","title":"Utility of ctDNA to support patient selection for early phase clinical trials: The TARGET Study","description":"Next generation sequencing (NGS) of circulating tumour DNA (ctDNA) supports blood-based genomic profiling but is not routinely implemented in the clinic. TARGET is a molecular profiling programme with the primary aim to match patients to early phase clinical trials based on analysis of both somatic mutations and copy number alterations (CNA) across a 641 cancer-associated gene panel in a single ctDNA assay. For the first 100 TARGET patients, ctDNA data showed good concordance with matched tumour and results were turned round within a clinically acceptable timeframe for Molecular Tumour Board (MTB) review. When applying a 2.5% Variant Allele Frequency (VAF) threshold actionable mutations were identified in 41/100 patients, with 11 of these patients going onto a matched therapy. These data support the application of ctDNA in an early phase trial setting where broad genomic profiling of contemporaneous tumour material enhances patient stratification to novel therapies and provides a practical template for bringing blood-based analyses to the clinic.","abstract":"Next generation sequencing (NGS) of circulating tumour DNA (ctDNA) supports blood-based genomic profiling but is not routinely implemented in the clinic. TARGET is a molecular profiling programme with the primary aim to match patients to early phase clinical trials based on analysis of both somatic mutations and copy number alterations (CNA) across a 641 cancer-associated gene panel in a single ctDNA assay. For the first 100 TARGET patients, ctDNA data showed good concordance with matched tumour and results were turned round within a clinically acceptable timeframe for Molecular Tumour Board (MTB) review. When applying a 2.5% Variant Allele Frequency (VAF) threshold actionable mutations were identified in 41/100 patients, with 11 of these patients going onto a matched therapy. These data support the application of ctDNA in an early phase trial setting where broad genomic profiling of contemporaneous tumour material enhances patient stratification to novel therapies and provides a practical template for bringing blood-based analyses to the clinic.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-21T13:51:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003408","title":"Methylation analysis of plasma DNA informs etiologies of Epstein-Barr virus-associated diseases","description":"Through whole-genome methylation analysis of plasma samples from patients with nasopharyngeal carcinoma (NPC), EBV-associated lymphoma and infectious mononucleosis, we demonstrate that EBV DNA methylation profiles exhibit a disease-associated pattern. Such observation implies significant potentials in the development of methylation analysis of plasma EBV DNA for NPC diagnostics.","abstract":"Through whole-genome methylation analysis of plasma samples from patients with nasopharyngeal carcinoma (NPC), EBV-associated lymphoma and infectious mononucleosis, we demonstrate that EBV DNA methylation profiles exhibit a disease-associated pattern. Such observation implies significant potentials in the development of methylation analysis of plasma EBV DNA for NPC diagnostics.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-26T13:05:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003409","title":"Plasma DNA motif analysis","description":"Plasma DNA motif analysis","abstract":"Plasma DNA motif analysis","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-26T13:07:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003410","title":"DNA methylation and gene expression profiling in multiple myeloma patients using eRRBS and genome-wide microarray analysis.","description":"Multiple Myeloma (MM) is a myelosuppressive hematological malignancy with extreme genomic heterogeneity and poor survival outcome. Here, we have mapped genome-wide DNA-methylation using an optimized enhanced Reduced Representation Bisulfite Sequencing (eRRBS). We have used  8 samples of t(4;14), 10 of t(11;14), 9 of t(14;16), 7 of t(14;20), 12 of HRD-D1 and 7 of HRD-D2 NDMM patients, compared to the 4 independent pool of age matched healthy donors. Briefly, DNA was digested with MspI followed by size selection of the library, providing enhanced coverage for the CpG-rich regions. The digested DNA was adapter ligated, bisulfite modified and PCR amplified. The libraries were sequenced on Illumina’s NextSeq 500. Analysis of the first samples sequenced in single-end mode. A minimum of 2 CpG sites per 100 bp region were considered significant for determining the differential methylation regions (DMRs). The promising DMRs were taken forward for the development and downstream analyses.","abstract":"Multiple Myeloma (MM) is a myelosuppressive hematological malignancy with extreme genomic heterogeneity and poor survival outcome. Here, we have mapped genome-wide DNA-methylation using an optimized enhanced Reduced Representation Bisulfite Sequencing (eRRBS). We have used  8 samples of t(4;14), 10 of t(11;14), 9 of t(14;16), 7 of t(14;20), 12 of HRD-D1 and 7 of HRD-D2 NDMM patients, compared to the 4 independent pool of age matched healthy donors. Briefly, DNA was digested with MspI followed by size selection of the library, providing enhanced coverage for the CpG-rich regions. The digested DNA was adapter ligated, bisulfite modified and PCR amplified. The libraries were sequenced on Illumina’s NextSeq 500. Analysis of the first samples sequenced in single-end mode. A minimum of 2 CpG sites per 100 bp region were considered significant for determining the differential methylation regions (DMRs). The promising DMRs were taken forward for the development and downstream analyses.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003411","title":"RNA sequencing of multiple myeloma identifies genes dysregulated by structural variants.","description":"Multiple myeloma is a disease of structural changes brought about by copy number abnormalities and translocations.  Many of these changes result in super-enhancers being placed next to key oncogenes.  Here, we have investigated which genes are commonly dysregulated by these changes.","abstract":"Multiple myeloma is a disease of structural changes brought about by copy number abnormalities and translocations.  Many of these changes result in super-enhancers being placed next to key oncogenes.  Here, we have investigated which genes are commonly dysregulated by these changes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-27T18:35:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003412","title":"Altered oligodendrocyte heterogeneity in Multiple sclerosis revealed by single nuclei RNA sequencing","description":"This study is currently hosted by the European Nucleotide Archive. To access the data contained within the Study please follow the link below:\n        https://www.ebi.ac.uk/ena/browser/view/PRJEB39323\nOligodendrocyte (OL) pathology is increasingly implicated in neurodegenerative diseases, as they are involved in metabolic support of axons and functional cross-talk with other brain cells. Rodent OLs are heterogeneous, with developmental and biological differences, but the extent of heterogeneity in the normal human brain and its contribution to any changes to disease remains unknown. Here we performed single nuclei RNA-sequencing (snRNA-seq) from white matter (WM) areas of post mortem human brain both in control (Ctr) and multiple sclerosis (MS) patients. We identified several sub-clusters of oligodendroglia in the Ctr human WM, some similar to those in mouse, and defined new markers for these cell states. Strikingly, some of these sub-clusters were under-represented in MS tissue, while others were more prevalent than in controls. We found a lack of OL precursor cells (OPCs) and an OL subcluster in an intermediate stage of differentiation in MS lesions and in normal appearing white matter (NAWM), suggesting either depletion by the disease or by a regenerative response. The differences in mature OL sub-clusters indicate different functional states of OLs in MS tissue and, as this is similar in NAWM to lesions, that MS is a more diffuse brain disease than the focal demyelinating lesions suggest. We were also able to identify new putative markers of different MS lesion subtypes. Our findings of an altered heterogeneity of oligodendroglia in MS may have an important contribution to our understanding of disease progression and may alter therapeutic approaches to MS.","abstract":"This study is currently hosted by the European Nucleotide Archive. To access the data contained within the Study please follow the link below:\n        https://www.ebi.ac.uk/ena/browser/view/PRJEB39323\nOligodendrocyte (OL) pathology is increasingly implicated in neurodegenerative diseases, as they are involved in metabolic support of axons and functional cross-talk with other brain cells. Rodent OLs are heterogeneous, with developmental and biological differences, but the extent of heterogeneity in the normal human brain and its contribution to any changes to disease remains unknown. Here we performed single nuclei RNA-sequencing (snRNA-seq) from white matter (WM) areas of post mortem human brain both in control (Ctr) and multiple sclerosis (MS) patients. We identified several sub-clusters of oligodendroglia in the Ctr human WM, some similar to those in mouse, and defined new markers for these cell states. Strikingly, some of these sub-clusters were under-represented in MS tissue, while others were more prevalent than in controls. We found a lack of OL precursor cells (OPCs) and an OL subcluster in an intermediate stage of differentiation in MS lesions and in normal appearing white matter (NAWM), suggesting either depletion by the disease or by a regenerative response. The differences in mature OL sub-clusters indicate different functional states of OLs in MS tissue and, as this is similar in NAWM to lesions, that MS is a more diffuse brain disease than the focal demyelinating lesions suggest. We were also able to identify new putative markers of different MS lesion subtypes. Our findings of an altered heterogeneity of oligodendroglia in MS may have an important contribution to our understanding of disease progression and may alter therapeutic approaches to MS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2018-12-31T17:49:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003413","title":"Immunogenomic characterization of multi-focal liver cancer","description":"Immunogenomic characterization of multi-focal liver cancer in Zhongshan hospital","abstract":"Immunogenomic characterization of multi-focal liver cancer in Zhongshan hospital","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003414","title":"Mutation tracking in single cell RNA-Seq reveals consequences of subclonal evolution in acute myeloid leukemia","description":"Total bone marrow from AML patients was FACS index sorted with staining for Lineage markers (Lin), CD33, CD34, CD38, CD45RA, CD90, CD99, Tim3 and GPR56, and enrichment for Lin- and Lin-CD34+ cells. Single cells were subjected to a modified smart-seq2 protocol with targeting of mutant sites of interest (\"MutaSeq”).","abstract":"Total bone marrow from AML patients was FACS index sorted with staining for Lineage markers (Lin), CD33, CD34, CD38, CD45RA, CD90, CD99, Tim3 and GPR56, and enrichment for Lin- and Lin-CD34+ cells. Single cells were subjected to a modified smart-seq2 protocol with targeting of mutant sites of interest (\"MutaSeq”).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-02T11:20:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003415","title":"Dissecting features of epigenetic variants underlying cardiometabolic risk using full-resolution epigenome profiling in regulatory elements","description":"Sparse profiling of CpG methylation in blood by microarrays have identified epigenetic links to common diseases. We apply methylC-capture sequencing (MCC-Seq) in a clinical population of ~200 adipose tissue and matched blood samples (Ntotal ~400), providing high-resolution methylation profiling (&amp;amp;gt;1.3M CpGs) at regulatory elements. We link methylation to cardiometabolic risk through associations to circulating plasma lipid levels and identify lipid-associated CpGs with unique localization patterns in regulatory elements. We show distinct features of tissue-specific versus tissue-independent lipid-linked regulatory regions by contrasting with parallel assessments in ~800 independent adipose tissue and blood samples from the general population. We follow-up on adipose-specific regulatory regions under (1) genetic and (2) epigenetic (environmental) regulation via integrational studies. Overall, the comprehensive sequencing of regulatory element methylomes reveals a rich landscape of functional variants linked genetically as well as epigenetically to plasma lipid traits.","abstract":"Sparse profiling of CpG methylation in blood by microarrays have identified epigenetic links to common diseases. We apply methylC-capture sequencing (MCC-Seq) in a clinical population of ~200 adipose tissue and matched blood samples (Ntotal ~400), providing high-resolution methylation profiling (&amp;amp;gt;1.3M CpGs) at regulatory elements. We link methylation to cardiometabolic risk through associations to circulating plasma lipid levels and identify lipid-associated CpGs with unique localization patterns in regulatory elements. We show distinct features of tissue-specific versus tissue-independent lipid-linked regulatory regions by contrasting with parallel assessments in ~800 independent adipose tissue and blood samples from the general population. We follow-up on adipose-specific regulatory regions under (1) genetic and (2) epigenetic (environmental) regulation via integrational studies. Overall, the comprehensive sequencing of regulatory element methylomes reveals a rich landscape of functional variants linked genetically as well as epigenetically to plasma lipid traits.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-02T22:26:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003416","title":"The genomic imprint of cancer therapies helps timing the formation of metastases","description":null,"abstract":"This study was based on the hypothesis that genomic alterations induced by cancer therapies could be used to determine the temporal order of the treatment and the formation of metastases. We analysed the whole genome sequence of a primary tumour sample and three metastatic sites derived from autopsy samples from a young never-smoker lung adenocarcinoma patient with an activating EGFR mutation.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003417","title":"iNeuron_scRNAseq","description":"Characterisation of differentiation of induced cortical excitatory neurons generated by overexpression of the Ngn2 transcription factor transgenically in BOB iPSCs. The aim is to understand the differentiation trajectory undergone in this process, and characterise the transcriptome in these cells for further disease modelling. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Characterisation of differentiation of induced cortical excitatory neurons generated by overexpression of the Ngn2 transcription factor transgenically in BOB iPSCs. The aim is to understand the differentiation trajectory undergone in this process, and characterise the transcriptome in these cells for further disease modelling. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003418","title":"Landscape of somatic mutations and DNA copy number alterations and transcriptomic profiling identifies metabolic reprogramming as a hallmark of ibrutinib resistance","description":"Whole-exome sequencing (WES) was conducted on the clinical specimens of 14 cases that had sufficient isolated tumor DNA, including 7 ibrutinib-sensitive cases and 7 ibrutinib-resistant cases. \n\nWhole transcriptome sequencing (RNA-seq) was performed on clinical specimens isolated from 14 ibrutinib-sensitive and 7 ibrutinib-resistant cases. Unsupervised hierarchical clustering of MCL tumors using RNA-seq gene expression data showed a response-specific gene expression signature.","abstract":"Whole-exome sequencing (WES) was conducted on the clinical specimens of 14 cases that had sufficient isolated tumor DNA, including 7 ibrutinib-sensitive cases and 7 ibrutinib-resistant cases. \n\nWhole transcriptome sequencing (RNA-seq) was performed on clinical specimens isolated from 14 ibrutinib-sensitive and 7 ibrutinib-resistant cases. Unsupervised hierarchical clustering of MCL tumors using RNA-seq gene expression data showed a response-specific gene expression signature.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-08T08:21:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003419","title":"16S-based fecal microbiota composition of the Milieu Intérieur Cohort","description":"The Milieu Intérieur project is a population-based study coordinated by the Institut Pasteur, Paris. The objective is to dissect the interplay between genetics and environment and their impact on the immune system. One of the primary goals of the project is to ascertain the role of the microbiota in regulating immune programs.","abstract":"The Milieu Intérieur project is a population-based study coordinated by the Institut Pasteur, Paris. The objective is to dissect the interplay between genetics and environment and their impact on the immune system. One of the primary goals of the project is to ascertain the role of the microbiota in regulating immune programs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-08T11:32:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003420","title":"scRNAseq_eQTLS_to_understand_genetic_predisposition_to_IBD","description":"Pilot study to test dissociation protocols for IBD relevant human gut tissues.","abstract":"In this project we will determine the utility of various inhibitors (actinomycin d, flavipirodol, Rocki and QVD) for preservation of human gut cell transcriptomes in their most natural state. Gut biopsies are obtained by endoscopy. Transcriptomes will be compared to flash frozen biopsies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003421","title":"STREP GENE: Genetics and Severe Streptococcal Infections","description":"This study investigated host genetic susceptibility to invasive group A streptococcal disease in the UK. Cases were either survivors recruited retrospectively through a patient group or identified from the a tissue bank at Imperial College London. Those recruited through the patient group had survived an episode of invasive GAS disease at a UK hospital since 1980 with microbiological confirmation obtained either through Public Health England or from the treating hospital.  Those identified from the tissue bank had been diagnosed with invasive GAS disease at the Hammersmith Hospital, London, UK, since 2006. All cases aged less than 65 years without long-term medical conditions genome-wide genotyped using either the Illumina HumanCore or the Global Screening Array platform.","abstract":"This study investigated host genetic susceptibility to invasive group A streptococcal disease in the UK. Cases were either survivors recruited retrospectively through a patient group or identified from the a tissue bank at Imperial College London. Those recruited through the patient group had survived an episode of invasive GAS disease at a UK hospital since 1980 with microbiological confirmation obtained either through Public Health England or from the treating hospital.  Those identified from the tissue bank had been diagnosed with invasive GAS disease at the Hammersmith Hospital, London, UK, since 2006. All cases aged less than 65 years without long-term medical conditions genome-wide genotyped using either the Illumina HumanCore or the Global Screening Array platform.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-09T13:23:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003422","title":"Synthetic_RNA_modulators_of_gene_function__a_pilot_study","description":"While the scale of GWAS, and number of discovered loci associated with traits has substantially increased over the past decade, functional validation, and understanding of underlying biology driving these associations has lagged behind; limiting translation of these discoveries into therapeutic applications. In this context, synthetic RNA modulators of gene function provide an efficient, and high-throughput mechanism for validation of discoveries in cellular models, providing a platform for interrogation and translation of findings from GWAS, into therapeutic applications within an integrated platform. An improvement in our understanding of the regulation of gene functions by different types of RNA modulators, and the technological development in the field of synthetic RNA molecules, has enabled high-throughput functional assays of cellular phenotypes in multiple cellular models, as well as opportunities to translate these discoveries directly into therapeutics. Complementary to this, recent development of deep learning approaches to effectively predict miRNA-target associations (Rayner et al., 2017) and promoter regions have provided a rich database of computationally predicted modulators of gene function for functional validation. We propose a high-throughput screen of 380 synthetic RNA molecules across 15 genes identified as associated with cardiometabolic and other traits through multiple lines of evidence (GWAS, eQTL, functional studies, and/or mouse phenotyping). We will use a range of synthetic RNA molecules to target a set of genes of interest in cellular models (HepG2 cell lines), to examine changes in target gene expression (efficacy), immunogenicity and cell-viability. Promoters will be identified through existing databases, and deep learning and bioinformatics approaches; we will also use predicted miRNA-target associations identified through deep learning frameworks trained on experimental evidence (Rayner et al., 2017), as part of an established collaboration. Alongside integrated genetic and EHR data, such datasets provide the opportunity to align multidimensional data to understand loci associated with disease, and identify potential therapeutic targets.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We carried out a high-throughput screen of 380 synthetic RNA molecules across 15 genes identified as associated with cardiometabolic and other traits through multiple lines of evidence (GWAS, eQTL, functional studies, and/or mouse phenotyping). We used a range of synthetic RNA molecules to target a set of genes of interest in cellular models (HepG2 cell lines), to examine changes in target gene expression (efficacy), immunogenicity and cell-viability. Promoters were identified through existing databases, and deep learning and bioinformatics approaches; we also used predicted miRNA-target associations identified through deep learning frameworks trained on experimental evidence (Rayner et al., 2017), as part of an established collaboration. Alongside integrated genetic and EHR data, such datasets provide the opportunity to align multidimensional data to understand loci associated with disease, and identify potential therapeutic targets.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003423","title":"Study the genetic susceptibility of esophagus squamous cell carcinomas (ESCC) in high-risk area Henan Chinese","description":"This study utilized a genetically-enriched cohort of patients with familial ESCC from the high-risk Henan region, located near the Tai-Hang Mountain region in Northern China, to identify high penetrance ESCC predisposition genes using a comprehensive unbiased whole-exome sequencing (WES) strategy. Subsequent validate the prevalence of rare damage variants by targeted gene sequencing in a large sample size.","abstract":"This study utilized a genetically-enriched cohort of patients with familial ESCC from the high-risk Henan region, located near the Tai-Hang Mountain region in Northern China, to identify high penetrance ESCC predisposition genes using a comprehensive unbiased whole-exome sequencing (WES) strategy. Subsequent validate the prevalence of rare damage variants by targeted gene sequencing in a large sample size.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-11T15:01:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003424","title":"Genome Wide Association Study:GR@ACE Stage I","description":"The Genome Research program at Fundacio ACE (GR@ACE, Barcelona, Spain), represents a new effort to study Alzheimer's Disease susceptibility. The GR@ACE study comprises 7,409 unrelated individuals. 4,120 AD cases were diagnosed at Fundació ACE Memory Clinic (Barcelona, Spain). 3,289 Controls were obtained from three collections (Fundació ACE, Barcelona; DNA National Biobank, Salamanca and HU Valme, Seville). Genotyping was carried out using the 815K Axiom Spain Biobank array (Affymetrix.) in the Spanish national center for genotyping (CEGEN, Santiago de Compostela, Spain). After genotyping, an extensive quality control was conducted, including re-sampling, gender match, stratification, relatedness, heterozygosity, differential missingness and HWD analyses.","abstract":"The Genome Research program at Fundacio ACE (GR@ACE, Barcelona, Spain), represents a new effort to study Alzheimer's Disease susceptibility. The GR@ACE study comprises 7,409 unrelated individuals. 4,120 AD cases were diagnosed at Fundació ACE Memory Clinic (Barcelona, Spain). 3,289 Controls were obtained from three collections (Fundació ACE, Barcelona; DNA National Biobank, Salamanca and HU Valme, Seville). Genotyping was carried out using the 815K Axiom Spain Biobank array (Affymetrix.) in the Spanish national center for genotyping (CEGEN, Santiago de Compostela, Spain). After genotyping, an extensive quality control was conducted, including re-sampling, gender match, stratification, relatedness, heterozygosity, differential missingness and HWD analyses.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-14T09:56:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003425","title":"the Yemeni-Somali 5 million SNP array dataset","description":"The three new samples (two from Yemen and one from Somalia) that carry a maternal lineage affiliated with the Malagasy motif were assayed for genome-wide SNP genotypes using the Illumina Human Omni5 Bead Chip (Illumina), which surveys 4,284,426 single nucleotide markers regularly spaced across the genome.","abstract":"The three new samples (two from Yemen and one from Somalia) that carry a maternal lineage affiliated with the Malagasy motif were assayed for genome-wide SNP genotypes using the Illumina Human Omni5 Bead Chip (Illumina), which surveys 4,284,426 single nucleotide markers regularly spaced across the genome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-14T13:58:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003426","title":"Panel-based next-generation sequencing study of human liver samples.","description":"Panel-based next-generation sequencing study of 150 human surgical liver samples from Caucasian donors with detailed medical documentation. The overall purpose of the study was to identify expression quantitative trait loci (eQTL) in human liver for genes involved in absorption, distribution, metabolism and excretion of drugs, other xenobiotics, and endogenous substances.","abstract":"Panel-based next-generation sequencing study of 150 human surgical liver samples from Caucasian donors with detailed medical documentation. The overall purpose of the study was to identify expression quantitative trait loci (eQTL) in human liver for genes involved in absorption, distribution, metabolism and excretion of drugs, other xenobiotics, and endogenous substances.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-14T15:45:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003427","title":"Combined MEK and BCL-2/XL inhibition is effective in high-grade serous ovarian cancer patient-derived xenograft models and BIM levels are predictive of responsiveness","description":"Most patients with late stage high-grade serous ovarian cancer (HGSOC) initially respond to chemotherapy but inevitably relapse and develop resistance, highlighting the need for novel therapies to improve patient outcomes. The MEK/ERK pathway is activated in a large subset of HGSOC, thus making it an attractive therapeutic target. Here, we systematically evaluated the extent of MEK/ERK pathway activation and efficacy of pathway inhibition in a large panel of well-annotated HGSOC patient-derived xenograft (PDX) models. The vast majority of models were nonresponsive to the MEK inhibitor cobimetinib (GDC-0973) despite effective pathway inhibition.  Proteomic analyses of adaptive responses to GDC-0973 revealed that GDC-0973 upregulated the pro-apoptotic protein BIM, thus priming the cells for apoptosis regulated by BCL2-family proteins. Indeed, combination of both MEK inhibitor and dual BCL-2/XL inhibitor (ABT-263) significantly reduced cell number, increased cell death and displayed synergy in vitro in most models. In vivo, the GDC-0973 and ABT-263 combination was well tolerated and resulted in greater tumor growth inhibition than single agents. Detailed proteomic and correlation analyses identified two subsets of responsive models – those with high BIM at baseline that was increased with MEK inhibition and those with low basal Bim and high pERK levels.  Models with low BIM and low pERK were non-responsive. Our findings demonstrate that combined MEK and BCL-2/XL inhibition has therapeutic activity in HGSOC models and provide a mechanistic rationale for clinical evaluation  of this drug combination as well as the assessment of the extent to which BIM and/or pERK levels predict drug combination effectiveness in chemoresistant HGSOC.","abstract":"Most patients with late stage high-grade serous ovarian cancer (HGSOC) initially respond to chemotherapy but inevitably relapse and develop resistance, highlighting the need for novel therapies to improve patient outcomes. The MEK/ERK pathway is activated in a large subset of HGSOC, thus making it an attractive therapeutic target. Here, we systematically evaluated the extent of MEK/ERK pathway activation and efficacy of pathway inhibition in a large panel of well-annotated HGSOC patient-derived xenograft (PDX) models. The vast majority of models were nonresponsive to the MEK inhibitor cobimetinib (GDC-0973) despite effective pathway inhibition.  Proteomic analyses of adaptive responses to GDC-0973 revealed that GDC-0973 upregulated the pro-apoptotic protein BIM, thus priming the cells for apoptosis regulated by BCL2-family proteins. Indeed, combination of both MEK inhibitor and dual BCL-2/XL inhibitor (ABT-263) significantly reduced cell number, increased cell death and displayed synergy in vitro in most models. In vivo, the GDC-0973 and ABT-263 combination was well tolerated and resulted in greater tumor growth inhibition than single agents. Detailed proteomic and correlation analyses identified two subsets of responsive models – those with high BIM at baseline that was increased with MEK inhibition and those with low basal Bim and high pERK levels.  Models with low BIM and low pERK were non-responsive. Our findings demonstrate that combined MEK and BCL-2/XL inhibition has therapeutic activity in HGSOC models and provide a mechanistic rationale for clinical evaluation  of this drug combination as well as the assessment of the extent to which BIM and/or pERK levels predict drug combination effectiveness in chemoresistant HGSOC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-15T11:28:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003428","title":"Genomic_profiling_of_B_other_Adult_ALL_RNA","description":"Adult ALL is an aggressive leukaemia, affecting adults of all ages. It is associated with a rapid onset and poor outcomes.  Our understanding of adult ALL genome has been limited to molecular markers first described in paediatric ALL and validated in adult ALL and to date there have been no studies investigating the genomics of Adult ALL. We will perform whole genome sequencing on at least 100 Adult ALL cases. Priority will be given on ALL cases without a known primary lesion by cytogenetic analysis which are categorised as “B-other”.  We will also sequence representative cases of each known subtype. This will deliver a comprehensive annotation of the genomic landscape of Adult ALL to include acquired somatic mutations (substitutions, indels, structural variants/fusion genes) and copy number profiles. The focus on B-other Adult ALL is likely to result in new and previously undescribed genomic lesions.","abstract":"Adult ALL is an aggressive leukaemia, affecting adults of all ages. It is associated with a rapid onset and poor outcomes.  Our understanding of adult ALL genome has been limited to molecular markers first described in paediatric ALL and validated in adult ALL and to date there have been no studies investigating the genomics of Adult ALL. We will perform whole genome sequencing on at least 100 Adult ALL cases. Priority will be given on ALL cases without a known primary lesion by cytogenetic analysis which are categorised as “B-other”.  We will also sequence representative cases of each known subtype. This will deliver a comprehensive annotation of the genomic landscape of Adult ALL to include acquired somatic mutations (substitutions, indels, structural variants/fusion genes) and copy number profiles. The focus on B-other Adult ALL is likely to result in new and previously undescribed genomic lesions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-16T09:36:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003429","title":"Activating mutations in the MAP-kinase pathway define non-ossifying fibroma of bone.","description":null,"abstract":"Using exome sequencing we have identified hotspot KRAS, FGFR1 and NF1 mutations in patientswith non-ossifying fibroma, at allele frequencies ranging from 0.04 to 0.61. These data support the definition of NOF as a genetically driven neoplasm caused in most cases by activated MAP-kinase signalling and form a part of a larger study PubMed ID 30549028.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003430","title":"Clinical genome sequencing uncovers potentially targetable truncations and fusions of MAP3K8 in spitzoid and other melanomas","description":"Spitzoid melanoma is a specific morphologic variant of melanoma that most commonly affects children and adolescents and ranges on the spectrum of malignancy from low-grade to overtly malignant. These tumors are generally driven by fusions of ALK, RET, NTRK1/3, MET, ROS1 and BRAF. However, in approximately 50% of cases, no genetic driver has been established. Clinical whole genome and transcriptome sequencing (RNA-Seq) of a spitzoid tumor from an adolescent revealed a novel gene fusion of MAP3K8, encoding a serine−threonine kinase that activates MEK. The patient who had exhausted all other therapeutic options was treated with a MEK inhibitor and underwent a transient clinical response. We subsequently analyzed spitzoid tumors from 49 patients by RNA-Seq and found in-frame fusions or C-terminal truncations in 33% of cases. The fusion transcripts and truncated genes all contained MAP3K8 exons 1-8 but lacked the autoinhibitory final exon. Data mining of RNA-Seq from the Cancer Genome Atlas (TCGA) uncovered analogous MAP3K8 rearrangements in 1.5% of adult melanomas. Thus, MAP3K8 rearrangements - uncovered by comprehensive clinical sequencing of a single case - are the most common genetic event in spitzoid melanoma, are present in adult melanomas, and could be amenable to MEK inhibition.","abstract":"Spitzoid melanoma is a specific morphologic variant of melanoma that most commonly affects children and adolescents and ranges on the spectrum of malignancy from low-grade to overtly malignant. These tumors are generally driven by fusions of ALK, RET, NTRK1/3, MET, ROS1 and BRAF. However, in approximately 50% of cases, no genetic driver has been established. Clinical whole genome and transcriptome sequencing (RNA-Seq) of a spitzoid tumor from an adolescent revealed a novel gene fusion of MAP3K8, encoding a serine−threonine kinase that activates MEK. The patient who had exhausted all other therapeutic options was treated with a MEK inhibitor and underwent a transient clinical response. We subsequently analyzed spitzoid tumors from 49 patients by RNA-Seq and found in-frame fusions or C-terminal truncations in 33% of cases. The fusion transcripts and truncated genes all contained MAP3K8 exons 1-8 but lacked the autoinhibitory final exon. Data mining of RNA-Seq from the Cancer Genome Atlas (TCGA) uncovered analogous MAP3K8 rearrangements in 1.5% of adult melanomas. Thus, MAP3K8 rearrangements - uncovered by comprehensive clinical sequencing of a single case - are the most common genetic event in spitzoid melanoma, are present in adult melanomas, and could be amenable to MEK inhibition.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-16T16:28:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003431","title":"An Integrated Framework for Genome Analysis Reveals Numerous Previously Unrecognizable Structural Variants in Leukemia Patients’ Samples","description":null,"abstract":"We have applied a combination of whole genome sequencing and optical genome mapping to a number of adult and pediatric leukemia samples, revealing a large number of structural variants not recognizable by current standard genomic analyses.  We developed computational methods to determine which of those variants likely arose as somatic mutations.  A number of variants only affected intergenic regions but caused cis-acting alterations in expression of neighboring genes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003432","title":"Whole genome sequencing with linked reads of pediatric glioblastoma samples","description":"Pediatric glioblastoma (pGBM) is a lethal cancer with no effective therapies. To understand mechanisms of tumor evolution in this cancer, we performed whole genome sequencing with linked reads on longitudinally resected pGBM samples. Our analyses showed that all diagnostic and recurrent samples were collections of genetically diverse subclones. Clonal composition rapidly evolved at recurrence, with less than 8% of non-synonymous single nucleotide variants being shared in diagnostic-recurrent pairs. In order to track the origins of the mutational events we observed in pGBM, we generated whole genome datasets for two patients and their parents. These trios showed that genetic variants could be (i) somatic, (ii) inherited from a healthy parent, or (iii) arose de novo in the germlines of pGBM patients. Analysis of variant allele frequencies supported a model of tumor growth involving slow-cycling cancer stem cells that give rise to fast-proliferating progenitor-like cells and to non-dividing cells. Interestingly, radiation and anti-mitotic chemotherapeutics did not increase overall tumor burden upon recurrence. These findings support an important role for slow-cycling stem cell populations in contributing to recurrences, since slow-cycling cell populations are expected to be less prone to genotoxic stress induced by these treatments and to accumulate few mutations. Our results highlight the need for new targeted treatments that account for the complex functional hierarchies and genomic heterogeneity of pGBM.","abstract":"Pediatric glioblastoma (pGBM) is a lethal cancer with no effective therapies. To understand mechanisms of tumor evolution in this cancer, we performed whole genome sequencing with linked reads on longitudinally resected pGBM samples. Our analyses showed that all diagnostic and recurrent samples were collections of genetically diverse subclones. Clonal composition rapidly evolved at recurrence, with less than 8% of non-synonymous single nucleotide variants being shared in diagnostic-recurrent pairs. In order to track the origins of the mutational events we observed in pGBM, we generated whole genome datasets for two patients and their parents. These trios showed that genetic variants could be (i) somatic, (ii) inherited from a healthy parent, or (iii) arose de novo in the germlines of pGBM patients. Analysis of variant allele frequencies supported a model of tumor growth involving slow-cycling cancer stem cells that give rise to fast-proliferating progenitor-like cells and to non-dividing cells. Interestingly, radiation and anti-mitotic chemotherapeutics did not increase overall tumor burden upon recurrence. These findings support an important role for slow-cycling stem cell populations in contributing to recurrences, since slow-cycling cell populations are expected to be less prone to genotoxic stress induced by these treatments and to accumulate few mutations. Our results highlight the need for new targeted treatments that account for the complex functional hierarchies and genomic heterogeneity of pGBM.","study_type":"Other","pubmed_ids":[30877103],"external_links":null,"is_released":true,"released_date":"2019-01-17T17:48:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003433","title":"Somatic_mutation_and_clonal_evolution_in_the_human_bladder_Novaseq","description":"In this study, we aim to characterise the landscape of mutation and clonal selection in the human bladder. The data in this study will be generated by whole-genome sequencing of laser-dissected microbiopsies from the bladder. The samples utilised in this study will include urothelium from transplant donors with no history of bladder cancer and cystectomy specimens from patients with bladder cancer.","abstract":"In this study, we aim to characterise the landscape of mutation and clonal selection in the human bladder. The data in this study will be generated by whole-genome sequencing of laser-dissected microbiopsies from the bladder. The samples utilised in this study will include urothelium from transplant donors with no history of bladder cancer and cystectomy specimens from patients with bladder cancer.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-18T13:14:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003434","title":"Extreme intratumor heterogeneity and driver evolution in mismatch repair deficient gastro-esophageal cancer","description":null,"abstract":"Mismatch repair deficient (dMMR) gastro-esophageal adenocarcinomas (GEAs) are a distinct subtype characterized by high immunotherapy sensitivity and better outcomes than MMR proficient counterparts. dMMR confers a hypermutator-phenotype that theoretically enables high evolvability but this has not been investigated by multi-region exome sequencing (MSeq). MSeq of four dMMR GEAs revealed extreme intratumor heterogeneity (ITH) (average: 1639 heterogeneous mutations/tumor), exceeding ITH in other solid tumor types &gt;20-fold. Long phylogenetic trunks (average: 685 mutations/tumor) likely explain the exquisite sensitivity to checkpoint-inhibiting immunotherapies. Driver mutations in TP53, ACVR2A, ARID1A/B, dMMR- and WNT-pathway genes recurrently located to the phylogenetic trunk. The hypermutator-phenotype remained active during cancer progression. Subclonal and parallel driver evolution predominated in PIK3CA, epigenetic regulator and immune evasion genes. Chromosomal instability evolved late in carcinogenesis or during cancer progression. Extreme ITH and subclonal driver evolution support high evolvability of dMMR GEAs. Truncal ARID1A mutations may offer novel therapeutic opportunities.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-21T10:06:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003435","title":"Trio exome sequencing identified null mutations in ITPA as the cause of Martsolf syndrome with a lethal dilated cardiomyopathy presenting in infancy","description":"Typical Martsolf syndrome is characterized by congenital cataracts, postnatal microcephaly, developmental delay, hypotonia, short stature and biallelic hypomorphic mutations in either RAB3GAP1 or RAB3GAP2. Genetic analysis of 85 unrelated “mutation negative” probands with Martsolf or Martsolf-like syndromes identified two individuals with different homozygous null mutations in ITPA, the gene encoding inosine triphosphate pyrophosphatase (ITPase).  Both probands were from multiplex families with a consistent, lethal and highly distinctive disorder; a Martsolf-like syndrome with infantile-onset dilated cardiomyopathy. Severe ITPase-deficiency has been previously reported with infantile epileptic encephalopathy (MIM 616647).  ITPase acts to prevent incorporation of inosine bases (rI/dI) into RNA and DNA. In Itpa-null cells dI was undetectable in genomic DNA.  dI could be identified at a low level in mtDNA without detectable mitochondrial genome instability, mtDNA depletion or biochemical dysfunction of the mitochondria. rI accumulation was detectable in proband-derived lymphoblastoid RNA. In Itpa-null mouse embryos rI was detectable in the brain and kidney with the highest level seen in the embryonic heart (rI at 1 in 385 bases). Transcriptome and proteome analysis in mutant cells revealed no major differences with controls. The rate of transcription and the total amount of cellular RNA also appeared normal. rI accumulation in RNA – and by implication rI production - correlates with the severity of organ dysfunction in ITPase deficiency but the basis of the cellulopathy remains cryptic.  While we cannot exclude cumulative minor effects, there are no major anomalies in the production, processing, stability and/or translation of mRNA.","abstract":"Typical Martsolf syndrome is characterized by congenital cataracts, postnatal microcephaly, developmental delay, hypotonia, short stature and biallelic hypomorphic mutations in either RAB3GAP1 or RAB3GAP2. Genetic analysis of 85 unrelated “mutation negative” probands with Martsolf or Martsolf-like syndromes identified two individuals with different homozygous null mutations in ITPA, the gene encoding inosine triphosphate pyrophosphatase (ITPase).  Both probands were from multiplex families with a consistent, lethal and highly distinctive disorder; a Martsolf-like syndrome with infantile-onset dilated cardiomyopathy. Severe ITPase-deficiency has been previously reported with infantile epileptic encephalopathy (MIM 616647).  ITPase acts to prevent incorporation of inosine bases (rI/dI) into RNA and DNA. In Itpa-null cells dI was undetectable in genomic DNA.  dI could be identified at a low level in mtDNA without detectable mitochondrial genome instability, mtDNA depletion or biochemical dysfunction of the mitochondria. rI accumulation was detectable in proband-derived lymphoblastoid RNA. In Itpa-null mouse embryos rI was detectable in the brain and kidney with the highest level seen in the embryonic heart (rI at 1 in 385 bases). Transcriptome and proteome analysis in mutant cells revealed no major differences with controls. The rate of transcription and the total amount of cellular RNA also appeared normal. rI accumulation in RNA – and by implication rI production - correlates with the severity of organ dysfunction in ITPase deficiency but the basis of the cellulopathy remains cryptic.  While we cannot exclude cumulative minor effects, there are no major anomalies in the production, processing, stability and/or translation of mRNA.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003436","title":"SHANK2 mutations associated with Autism Spectrum Disorder cause hyperconnectivity of human neurons","description":"Heterozygous loss-of-function mutations in the synaptic scaffolding gene SHANK2 are strongly associated with autism spectrum disorder (ASD). To investigate their effect on synaptic connectivity, we generated cortical neurons from induced pluripotent stem cells (iPSC) derived from neurotypic and ASD-affected donors. We developed Sparse coculture for Connectivity (SparCon) assays where SHANK2 and control neurons were differentially labeled and sparsely seeded together on a lawn of unlabeled control neurons. We observed striking increases in dendrite length, dendrite complexity, total synapse number, and frequency of spontaneous excitatory postsynaptic currents. These findings were phenocopied in gene-edited homozygous SHANK2 knockout cells and rescued by gene correction of an ASD SHANK2 muation, supporting a role for SHANK2 as a regulator of connectivity in developing human neurons. Dendrite length increases were exacerbated by IGF1, TG003, or BDNF, and suppressed by DHPG treatment. The transcriptome in these isogenic SHANK2 neurons was deeply perturbed in synapse, plasticity, and neuronal morphogenesis gene sets and ASD gene modules, and activity-dependent dendrite extension was impaired. Our unexpected findings provide evidence for hyperconnectivity and profoundly altered transcriptome in SHANK2 neurons derived from ASD subjects.","abstract":"Heterozygous loss-of-function mutations in the synaptic scaffolding gene SHANK2 are strongly associated with autism spectrum disorder (ASD). To investigate their effect on synaptic connectivity, we generated cortical neurons from induced pluripotent stem cells (iPSC) derived from neurotypic and ASD-affected donors. We developed Sparse coculture for Connectivity (SparCon) assays where SHANK2 and control neurons were differentially labeled and sparsely seeded together on a lawn of unlabeled control neurons. We observed striking increases in dendrite length, dendrite complexity, total synapse number, and frequency of spontaneous excitatory postsynaptic currents. These findings were phenocopied in gene-edited homozygous SHANK2 knockout cells and rescued by gene correction of an ASD SHANK2 muation, supporting a role for SHANK2 as a regulator of connectivity in developing human neurons. Dendrite length increases were exacerbated by IGF1, TG003, or BDNF, and suppressed by DHPG treatment. The transcriptome in these isogenic SHANK2 neurons was deeply perturbed in synapse, plasticity, and neuronal morphogenesis gene sets and ASD gene modules, and activity-dependent dendrite extension was impaired. Our unexpected findings provide evidence for hyperconnectivity and profoundly altered transcriptome in SHANK2 neurons derived from ASD subjects.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-21T16:24:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003437","title":"Paediatric Tumour Profiling","description":"Paediatric Tumour Profiling","abstract":"Paediatric Tumour Profiling","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-21T23:17:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003438","title":"Intratumoural Heterogeneity Underlies Distinct Therapy Responses and Treatment Resistance in Glioblastoma","description":"Glioblastomas are the most common and lethal neoplasms of the central nervous system. Neighbouring glioma cells maintain extreme degrees of genetic and phenotypic variation that forms intratumoural heterogeneity. This genetic diversity allows the most adaptive tumour clones to show treatment resistance and conserve the tumour bulk. We aimed to model this phenomenon and  test  the  effectiveness  of  several  targeted  therapeutic  interventions  to  overcome  therapy resistance. Heterogenic tumour masses were first deconstructed into single tumour cells, which were  expanded  independently  as  single-cell  clones.  SNP  arrays,  whole-genome  and  RNA sequencing, and CpG methylation analysis validated the unique molecular profile of each tumour clone, which displayed distinct pathologic features, including cell morphology, growth rate, and resistance to temozolomide and ionizing radiation. We also identified variable sensitivities to AURK, CDK, and EGFR inhibitors, consistent with the heterogenic molecular alterations that each clone  harboured.  These  targeted  therapies  effectively  eliminated  the  temozolomide-  and/or irradiation-resistant clones and also parental polyclonal cells. Our findings indicate that polyclonal tumours create a dynamic environment that consists of diverse tumour elements and treatment responses. Designing targeted therapies based on a range of molecular profiles can be a more effective strategy to eradicate treatment resistance, recurrence, and metastasis.","abstract":"Glioblastomas are the most common and lethal neoplasms of the central nervous system. Neighbouring glioma cells maintain extreme degrees of genetic and phenotypic variation that forms intratumoural heterogeneity. This genetic diversity allows the most adaptive tumour clones to show treatment resistance and conserve the tumour bulk. We aimed to model this phenomenon and  test  the  effectiveness  of  several  targeted  therapeutic  interventions  to  overcome  therapy resistance. Heterogenic tumour masses were first deconstructed into single tumour cells, which were  expanded  independently  as  single-cell  clones.  SNP  arrays,  whole-genome  and  RNA sequencing, and CpG methylation analysis validated the unique molecular profile of each tumour clone, which displayed distinct pathologic features, including cell morphology, growth rate, and resistance to temozolomide and ionizing radiation. We also identified variable sensitivities to AURK, CDK, and EGFR inhibitors, consistent with the heterogenic molecular alterations that each clone  harboured.  These  targeted  therapies  effectively  eliminated  the  temozolomide-  and/or irradiation-resistant clones and also parental polyclonal cells. Our findings indicate that polyclonal tumours create a dynamic environment that consists of diverse tumour elements and treatment responses. Designing targeted therapies based on a range of molecular profiles can be a more effective strategy to eradicate treatment resistance, recurrence, and metastasis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-22T06:16:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003439","title":"Multi-region exome sequencing of lung adenocarcinoma precursors -1","description":"To characterize the genomic landscape of invasive lung adenocarcinoma and its precursors; to depict the genomic evolution from preneoplasia of lung to invasive lung adenocarcinoma; to decipher mechanism to drive the tumor progression.","abstract":"To characterize the genomic landscape of invasive lung adenocarcinoma and its precursors; to depict the genomic evolution from preneoplasia of lung to invasive lung adenocarcinoma; to decipher mechanism to drive the tumor progression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-22T18:37:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003440","title":"Lymphocyte_bulk_targeted","description":"We study lymphocyte somatic evolution through the sequencing of normal healthy lymphocytes. We perform targeted sequencing of bulk pools of T and B cell subsets, using custom bait sets designed to cover known somatic mutations per individual (previously identified by WGS of single-cell derived colonies). The lineages of T and B cells, and the frequencies of these mutations reveals the neutral and non-neutral evolutionary processes underlying lymphocyte growth and function.","abstract":"As we age, our cells accumulate mutations, termed \"somatic mutations\". Somatic mutations, which exist in mosaic form throughout the body, are a direct record of the evolution of our cells. Some of these mutations are subject to neutral evolution. The study of neutral mutations can reveal the cell lineages resulting from normal development and tissue maintenance, and help us understand key demographic parameter of somatic evolution, such as population size and migration. Other mutations are under selection, resulting in the expansion or contraction of lineages. These mutations can lead to disease, such as cancer; however, the extent of selection on somatic mutations in not understood. We aim to understand the somatic evolution of the primary cells of the adaptive immune system, lymphocytes. As we age, lymphocytes accumulate somatic mutations, which reveal the evolutionary history of lymphocytes, as well as providing information about the particular mutations and lineage structures that contribute to age-related immune disorder. In order to understand somatic evolution in lymphocytes, we sequence lymphocytes from normal, healthy individuals across a range of ages. We perform whole-genome sequencing of single-cell derived T and B cell colonies to identify somatic mutations, and perform targeted deep-sequencing of these mutations. The lineages of T and B cells, and the frequencies of these mutations reveals the neutral and non-neutral evolutionary processes underlying lymphocyte growth.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003441","title":"Lymphocyte_LCM_NovaSeq","description":"Using whole genome sequencing of lymphocytes excised from human tissue using laser capture microscopy (LCM), we identify the mutations arising in these microenvironments. Sequencing of these samples will be done on the NovaSeq platform, using the whole exome kit. This work will contribute towards developing a catalog of mutations present in tissue resident lymphocytes across a range of tissues, and will characterize the mutational signatures that result from each microenvironment.","abstract":"As we age, our cells accumulate mutations, termed \"somatic mutations\". Somatic mutations, which exist in mosaic form throughout the body, are a direct record of the evolution of our cells. Some of these mutations are subject to neutral evolution. The study of neutral mutations can reveal the cell lineages resulting from normal development and tissue maintenance, and help us understand key demographic parameter of somatic evolution, such as population size and migration. Other mutations are under selection, resulting in the expansion or contraction of lineages. These mutations can lead to disease, such as cancer; however, the extent of selection on somatic mutations in not understood. We aim to understand the somatic evolution of the primary cells of the adaptive immune system, lymphocytes. As we age, lymphocytes accumulate somatic mutations, which reveal the evolutionary history of lymphocytes, as well as providing information about the particular mutations and lineage structures that contribute to age-related immune disorder. In order to understand somatic evolution in lymphocytes, we sequence lymphocytes from normal, healthy individuals across a range of ages. We perform whole-genome sequencing of LCM excised T and B cell colonies to identify somatic mutations, and perform targeted deep-sequencing of these mutations. The lineages of T and B cells, and the frequencies of these mutations reveals the neutral and non-neutral evolutionary processes underlying lymphocyte growth.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003442","title":"Functional and genomic heterogeneity of long-term self-renewing compartment as the origin of treatment resistance in pancreatic tumors","description":"Adaptive drug-resistance mechanisms allow human tumors to evade treatment through selection and expansion of treatment-resistant clones. Here, studying clonal evolution of tumor cells derived from human pancreatic tumors, we demonstrate that in vitro cultures and in vivo tumors are maintained by a common set of tumorigenic cells that can be used to establish clonal replica tumors (CRTs), large cohorts of animals bearing human tumors with identical clonal composition. Using CRTs to conduct quantitative assessments of adaptive responses to therapeutics, we uncovered a multitude of functionally heterogeneous subpopulations of cells with differential degrees of drug sensitivity. High-throughput isolation and deep characterization of unique clonal lineages showed genetic and transcriptomic diversity underlying functionally diverse subpopulations. Molecular annotation of gemcitabine-naïve clonal lineages with distinct responses to treatment in the context of CRTs generated signatures that can predict the response to chemotherapy, representing a potential biomarker to stratify patients with pancreatic cancer.\n\nRNA-Seq data on these clones are available on EBI ENA, under accession number: PRJEB27735.","abstract":"Adaptive drug-resistance mechanisms allow human tumors to evade treatment through selection and expansion of treatment-resistant clones. Here, studying clonal evolution of tumor cells derived from human pancreatic tumors, we demonstrate that in vitro cultures and in vivo tumors are maintained by a common set of tumorigenic cells that can be used to establish clonal replica tumors (CRTs), large cohorts of animals bearing human tumors with identical clonal composition. Using CRTs to conduct quantitative assessments of adaptive responses to therapeutics, we uncovered a multitude of functionally heterogeneous subpopulations of cells with differential degrees of drug sensitivity. High-throughput isolation and deep characterization of unique clonal lineages showed genetic and transcriptomic diversity underlying functionally diverse subpopulations. Molecular annotation of gemcitabine-naïve clonal lineages with distinct responses to treatment in the context of CRTs generated signatures that can predict the response to chemotherapy, representing a potential biomarker to stratify patients with pancreatic cancer.\n\nRNA-Seq data on these clones are available on EBI ENA, under accession number: PRJEB27735.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-23T22:46:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003443","title":"Reconstituting the transcriptome and DNA methylome landscapes of human implantation at single-cell resolution","description":"Implantation is a milestone event during mammalian embryogenesis. Due to the extreme difficulty of obtaining in vivo human early post-implantation embryos, the gene regulatory network and epigenetics controlling human embryo implantation remains elusive. Here, combining an in vitro culture system for human post-implantation development and single-cell omics sequencing technologies, over 10,000 single cells at five representative stages of pre/post-implantation development were systematically analyzed. Unsupervised dimensionality reduction and clustering algorithm of the transcriptome data show stepwise implantation routes for the epiblast, primitive endoderm, and trophectoderm lineages, suggesting preparation for the establishment of a mother-to-offspring connection after implantation. Female embryos showed asynchronous progress of dosage loss of X chromosomes during implantation. Furthermore, using the single cell trio-Seq (scTrio-Seq) strategy, re-methylation of the genomes of all the three lineages was unambiguously revealed. Surprisingly, the genome re-methylation of PE lineage were much slower than both EPI and TE lineages during the implantation process, indicating distinct methylome features between EPI and PE although both of which were derived from ICM. Collectively, our work paves the way for understanding the complex molecular mechanisms that regulate human embryo implantation, informing new insights and future efforts in early embryonic development and reproductive medicine.","abstract":"Implantation is a milestone event during mammalian embryogenesis. Due to the extreme difficulty of obtaining in vivo human early post-implantation embryos, the gene regulatory network and epigenetics controlling human embryo implantation remains elusive. Here, combining an in vitro culture system for human post-implantation development and single-cell omics sequencing technologies, over 10,000 single cells at five representative stages of pre/post-implantation development were systematically analyzed. Unsupervised dimensionality reduction and clustering algorithm of the transcriptome data show stepwise implantation routes for the epiblast, primitive endoderm, and trophectoderm lineages, suggesting preparation for the establishment of a mother-to-offspring connection after implantation. Female embryos showed asynchronous progress of dosage loss of X chromosomes during implantation. Furthermore, using the single cell trio-Seq (scTrio-Seq) strategy, re-methylation of the genomes of all the three lineages was unambiguously revealed. Surprisingly, the genome re-methylation of PE lineage were much slower than both EPI and TE lineages during the implantation process, indicating distinct methylome features between EPI and PE although both of which were derived from ICM. Collectively, our work paves the way for understanding the complex molecular mechanisms that regulate human embryo implantation, informing new insights and future efforts in early embryonic development and reproductive medicine.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-24T12:44:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003444","title":"Analysis of error profiles in deep next-generation sequencing data","description":"BackgroundSequencing errors are key confounding factors for detecting low-frequency genetic variants that are important for cancer molecular diagnosis, treatment, and surveillance using deep next-generation sequencing (NGS). However, there is a lack of comprehensive understanding of errors introduced at various steps of a conventional NGS workflow, such as sample handling, library preparation, PCR enrichment, and sequencing. In this study, we use current NGS technology to systematically investigate these questions.ResultsBy evaluating read-specific error distributions, we discover that the substitution error rate can be computationally suppressed to 10-5 to 10-4, which is 10- to 100-fold lower than generally considered achievable (10-3) in the current literature. We then quantify substitution errors attributable to sample handling, library preparation, enrichment PCR, and sequencing by using multiple deep sequencing datasets. We find that error rates differ by nucleotide substitution types, ranging from 10-5 for A&gt;C/T&gt;G, C&gt;A/G&gt;T, and C&gt;G/G&gt;C changes to 10-4 for A&gt;G/T&gt;C changes. Furthermore, C&gt;T/G&gt;A errors exhibit strong sequence context dependency, sample-specific effects dominate elevated C&gt;A/G&gt;T errors, and target enrichment PCR led to aprox 6-fold increase of overall error rate. We also find that more than 70% of hotspot variants can be detected at 0.1% - 0.01% frequency with the current NGS technology by applying in-silico error suppression.ConclusionsWe present the first comprehensive analysis of sequencing error sources in conventional NGS workflows. The error profiles revealed by our study highlight new directions for further improving NGS analysis accuracy both experimentally and computationally, ultimately enhancing the precision of deep sequencing.","abstract":"BackgroundSequencing errors are key confounding factors for detecting low-frequency genetic variants that are important for cancer molecular diagnosis, treatment, and surveillance using deep next-generation sequencing (NGS). However, there is a lack of comprehensive understanding of errors introduced at various steps of a conventional NGS workflow, such as sample handling, library preparation, PCR enrichment, and sequencing. In this study, we use current NGS technology to systematically investigate these questions.ResultsBy evaluating read-specific error distributions, we discover that the substitution error rate can be computationally suppressed to 10-5 to 10-4, which is 10- to 100-fold lower than generally considered achievable (10-3) in the current literature. We then quantify substitution errors attributable to sample handling, library preparation, enrichment PCR, and sequencing by using multiple deep sequencing datasets. We find that error rates differ by nucleotide substitution types, ranging from 10-5 for A&gt;C/T&gt;G, C&gt;A/G&gt;T, and C&gt;G/G&gt;C changes to 10-4 for A&gt;G/T&gt;C changes. Furthermore, C&gt;T/G&gt;A errors exhibit strong sequence context dependency, sample-specific effects dominate elevated C&gt;A/G&gt;T errors, and target enrichment PCR led to aprox 6-fold increase of overall error rate. We also find that more than 70% of hotspot variants can be detected at 0.1% - 0.01% frequency with the current NGS technology by applying in-silico error suppression.ConclusionsWe present the first comprehensive analysis of sequencing error sources in conventional NGS workflows. The error profiles revealed by our study highlight new directions for further improving NGS analysis accuracy both experimentally and computationally, ultimately enhancing the precision of deep sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-24T19:39:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003445","title":"Orphan_Tumour_Study_NB","description":"The aim of this study is to investigate the transcriptional landscape of human cancer.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The aim of this study is to investigate the transcriptional landscape of human cancer.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-25T11:06:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003446","title":"Liver_Tumours_WGS","description":"The aim of this study is to define the mutational landscape of human liver tumours.","abstract":"The aim of this study is to define the mutational landscape of human liver tumours.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-25T15:03:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003447","title":"Clonal architectures predict clinical outcome in clear cell renal cell carcinoma","description":"We analyze the clonal architectures of ccRCC patients from three different populations, including TCGA, Japanese and Chinese patients. We characterize the mutational signatures across different populations and evolution stages. The TCGA and Japanese data sets were downloaded from published studies and we also generated the whole genome sequencing data for more than 40 Chinese patients.","abstract":"We analyze the clonal architectures of ccRCC patients from three different populations, including TCGA, Japanese and Chinese patients. We characterize the mutational signatures across different populations and evolution stages. The TCGA and Japanese data sets were downloaded from published studies and we also generated the whole genome sequencing data for more than 40 Chinese patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-26T00:58:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003448","title":"Genomic landscape of lymphoepithelioma-like hepatocellular carcinoma","description":"Lymphoepithelioma-like carcinomas (LELC) are rare tumors that are characterized by a dense infiltration of tumor-associated lymphocytes, and often carry a good prognosis in patients. Lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is an uncommon variant of HCC with little known about its pathogenesis and patterns of genomic alterations. In this study, we conducted whole-exome sequencing (WES) on a series of 12 cases LEL-HCC and compared findings to 15 cases of conventional HCC (Conven-HCC) that were sequenced in parallel. Overall, there were no significant difference in the somatic mutational burdens between LEL-HCC and Conven-HCC, except for a higher number of somatic insertion–deletion (indel) alterations suggested in LEL-HCC. The frequency of some specific genes (CTNNB1, AXIN1, NOTCH1, NOTCH2) was significantly lower in LEL-HCC than in Conven-HCC, suggesting a correlation between activation of the Wnt/β-catenin and Notch signaling pathway and lower recruitment of T-Cell Infiltration. At the CNV level, we found a higher incidence of chr.11q13.3 amplification in LEL-HCC cases (25% LEL-HCC vs 6.7% Conven-HCC). Using TCGA datasets, we further established that well-known driver genes expressed from chr.11q13.3 including CCND1 and FGF19 showed strong association with common immune response genes (such as CD8A and IFN-γ) within the tumor microenvironment. Our results illustrate for the first time the somatic landscape of LEL-HCC, and highlight molecular alterations that are likely drivers in this tumor type.","abstract":"Lymphoepithelioma-like carcinomas (LELC) are rare tumors that are characterized by a dense infiltration of tumor-associated lymphocytes, and often carry a good prognosis in patients. Lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is an uncommon variant of HCC with little known about its pathogenesis and patterns of genomic alterations. In this study, we conducted whole-exome sequencing (WES) on a series of 12 cases LEL-HCC and compared findings to 15 cases of conventional HCC (Conven-HCC) that were sequenced in parallel. Overall, there were no significant difference in the somatic mutational burdens between LEL-HCC and Conven-HCC, except for a higher number of somatic insertion–deletion (indel) alterations suggested in LEL-HCC. The frequency of some specific genes (CTNNB1, AXIN1, NOTCH1, NOTCH2) was significantly lower in LEL-HCC than in Conven-HCC, suggesting a correlation between activation of the Wnt/β-catenin and Notch signaling pathway and lower recruitment of T-Cell Infiltration. At the CNV level, we found a higher incidence of chr.11q13.3 amplification in LEL-HCC cases (25% LEL-HCC vs 6.7% Conven-HCC). Using TCGA datasets, we further established that well-known driver genes expressed from chr.11q13.3 including CCND1 and FGF19 showed strong association with common immune response genes (such as CD8A and IFN-γ) within the tumor microenvironment. Our results illustrate for the first time the somatic landscape of LEL-HCC, and highlight molecular alterations that are likely drivers in this tumor type.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003449","title":"Single-cell RNA sequencing on single CD45+ immune cells isolated from peripheral blood, lymphnode, ascites, tumour and adjacent normal tissues from six hepatocellular carcinoma patients.","description":"Single-cell RNA sequencing on  single CD45+ immune cells isolated from peripheral blood, lymphnode, ascites, tumour and adjacent normal tissues from six hepatocellular carcinoma patients. The transcriptional properties of these individual cells, were used to delineate the molecular subtypes, lineage, and functional properties of each cell group","abstract":"Single-cell RNA sequencing on  single CD45+ immune cells isolated from peripheral blood, lymphnode, ascites, tumour and adjacent normal tissues from six hepatocellular carcinoma patients. The transcriptional properties of these individual cells, were used to delineate the molecular subtypes, lineage, and functional properties of each cell group","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-27T06:05:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003450","title":"MCO colorectal cancer genomics at UNSW","description":"This dataset contains DNA sequencing data from 95 colorectal cancer and matched-normal samples. The dataset contains targeted deep sequencing of selected regulatory elements in 95 cancer and matched-normal samples, and data for one sample that was additionally whole-genome sequenced (cancer and matched-normal).","abstract":"This dataset contains DNA sequencing data from 95 colorectal cancer and matched-normal samples. The dataset contains targeted deep sequencing of selected regulatory elements in 95 cancer and matched-normal samples, and data for one sample that was additionally whole-genome sequenced (cancer and matched-normal).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-28T07:32:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003451","title":"RNA-seq of M-CSF differentiated human peripheral monocyte-derived macrophages (MDMs) - Validation macIDR","description":"Macrophages represent multifunctional leukocytes defined by their stimulus-specific transcriptional reprogramming. As in vivo macrophages are often difficult to obtain, in vitro macrophage models are often used. We aggregated public expression data to define consensus expression profiles for eight commonly-used in vitro macrophage models and built the classifier macIDR, capable of distinguishing macrophage subsets with high accuracy (&gt;0.95). Classification of in vivo macrophages suggested that alveolar macrophages resembled interleukin-10 activated macrophages in general whereas chronic obstructive pulmonary disease patients displayed decreased similarity to interferon-γ stimulated macrophages. Adipose tissue-derived macrophages were classified as unstimulated macrophages, but would resemble LPS-stimulated macrophages more in diabetic-obese patients. Rheumatoid arthritic synovial macrophages were similar to macrophages stimulated with interleukin-10 or interferon-γ. Altogether, our results suggest that macIDR is capable of identifying in vitro macrophages. By projecting in vivo macrophages onto the in vitro macrophages, we were capable of elucidating macrophage-specific changes as a result of tissue and disease.","abstract":"Macrophages represent multifunctional leukocytes defined by their stimulus-specific transcriptional reprogramming. As in vivo macrophages are often difficult to obtain, in vitro macrophage models are often used. We aggregated public expression data to define consensus expression profiles for eight commonly-used in vitro macrophage models and built the classifier macIDR, capable of distinguishing macrophage subsets with high accuracy (&gt;0.95). Classification of in vivo macrophages suggested that alveolar macrophages resembled interleukin-10 activated macrophages in general whereas chronic obstructive pulmonary disease patients displayed decreased similarity to interferon-γ stimulated macrophages. Adipose tissue-derived macrophages were classified as unstimulated macrophages, but would resemble LPS-stimulated macrophages more in diabetic-obese patients. Rheumatoid arthritic synovial macrophages were similar to macrophages stimulated with interleukin-10 or interferon-γ. Altogether, our results suggest that macIDR is capable of identifying in vitro macrophages. By projecting in vivo macrophages onto the in vitro macrophages, we were capable of elucidating macrophage-specific changes as a result of tissue and disease.","study_type":"Other","pubmed_ids":[31921150],"external_links":null,"is_released":true,"released_date":"2019-01-28T13:57:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003452","title":"Probabilistic cell type assignment of single-cell transcriptomic data reveals spatiotemporal microenvironment dynamics in human cancers","description":"Single-cell RNA sequencing (scRNA-seq) has transformed biomedical research, enabling decomposition of complex tissues into disaggregated, functionally distinct cell types. For many applications, investigators wish to identify cell types with known marker genes. Typically, such cell type assignments are performed through unsupervised clustering followed by manual annotation based on these marker genes, or via \"mapping\" procedures to existing data. However, the manual interpretation required in the former case scales poorly to large datasets, which are also often prone to batch effects, while existing data for purified cell types must be available for the latter. Furthermore, unsupervised clustering can be error-prone, leading to under- and over- clustering of the cell types of interest. To overcome these issues we present CellAssign, a probabilistic model that leverages prior knowledge of cell type marker genes to annotate scRNA-seq data into pre-defined and de novo cell types. CellAssign automates the process of assigning cells in a highly scalable manner across large datasets while simultaneously controlling for batch and patient effects. We demonstrate the analytical advantages of CellAssign through extensive simulations and exemplify real-world utility to profile the spatial dynamics of high-grade serous ovarian cancer and the temporal dynamics of follicular lymphoma. Our analysis reveals subclonal malignant phenotypes and points towards an evolutionary interplay between immune and cancer cell populations with cancer cells escaping immune recognition.","abstract":"Single-cell RNA sequencing (scRNA-seq) has transformed biomedical research, enabling decomposition of complex tissues into disaggregated, functionally distinct cell types. For many applications, investigators wish to identify cell types with known marker genes. Typically, such cell type assignments are performed through unsupervised clustering followed by manual annotation based on these marker genes, or via \"mapping\" procedures to existing data. However, the manual interpretation required in the former case scales poorly to large datasets, which are also often prone to batch effects, while existing data for purified cell types must be available for the latter. Furthermore, unsupervised clustering can be error-prone, leading to under- and over- clustering of the cell types of interest. To overcome these issues we present CellAssign, a probabilistic model that leverages prior knowledge of cell type marker genes to annotate scRNA-seq data into pre-defined and de novo cell types. CellAssign automates the process of assigning cells in a highly scalable manner across large datasets while simultaneously controlling for batch and patient effects. We demonstrate the analytical advantages of CellAssign through extensive simulations and exemplify real-world utility to profile the spatial dynamics of high-grade serous ovarian cancer and the temporal dynamics of follicular lymphoma. Our analysis reveals subclonal malignant phenotypes and points towards an evolutionary interplay between immune and cancer cell populations with cancer cells escaping immune recognition.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-28T19:46:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003453","title":"Molecular profiling of blastic plasmacytoid dendritic cell neoplasm (BPDCN) as compared to acute myeloid leukemia (AML)","description":"Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, male-predominant myeloid malignancy that is characterized by the malignant proliferation of precursor plasmacytoid dendritic cells (pDCs) with morphologic and molecular similarities to acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in its presentation within the bone marrow and peripheral blood. To identify disease-specific molecular features of BPDCN, we profiled bone marrow, peripheral blood and serum samples from primary patient samples using an in-house hematologic malignancy panel (“T300” panel), transcriptome microarray, and serum multiplex immunoassays and compared results to a cohort of AML patients.","abstract":"Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, male-predominant myeloid malignancy that is characterized by the malignant proliferation of precursor plasmacytoid dendritic cells (pDCs) with morphologic and molecular similarities to acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in its presentation within the bone marrow and peripheral blood. To identify disease-specific molecular features of BPDCN, we profiled bone marrow, peripheral blood and serum samples from primary patient samples using an in-house hematologic malignancy panel (“T300” panel), transcriptome microarray, and serum multiplex immunoassays and compared results to a cohort of AML patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-29T16:08:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003454","title":"Molecular Phenotype of Constitutional TET2 Haploinsufficiency in Humans","description":"In this study, we observed the effects of constitutional heterozygous TET2 loss on blood DNA methylation, chromatin activity and gene expression in carriers of truncating TET2 germline mutations. To provide additional context to findings in TET2 mutation carriers, we analysed DNA methylation in four DNMT3A germline mutation carriers and their age-matched controls.","abstract":"In this study, we observed the effects of constitutional heterozygous TET2 loss on blood DNA methylation, chromatin activity and gene expression in carriers of truncating TET2 germline mutations. To provide additional context to findings in TET2 mutation carriers, we analysed DNA methylation in four DNMT3A germline mutation carriers and their age-matched controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-31T09:14:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003455","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__Colorectal_LCM","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-31T09:53:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003456","title":"Somatic_mutation_and_clonal_evolution_in_the_human_bladder_WES_NOVASEQ","description":"n this study, we aim to characterise the landscape of mutation and clonal selection in the human bladder. The study includes targeted sequencing of laser-dissected microbiopsies from the bladder. The samples utilised in this study will include urothelium from transplant donors with no history of bladder cancer and cystectomy specimens from patients with bladder cancer.","abstract":"n this study, we aim to characterise the landscape of mutation and clonal selection in the human bladder. The study includes targeted sequencing of laser-dissected microbiopsies from the bladder. The samples utilised in this study will include urothelium from transplant donors with no history of bladder cancer and cystectomy specimens from patients with bladder cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-01-31T14:43:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003457","title":"GermCellTumour","description":"DNA and RNA sequencing across a number of different germ cell tumours, included mixed components within the same tumour.","abstract":"This study aims to characterise the genetic and transcriptomic profile of germ cell tumours, in particular to develop a phylogenetic tree within mixed germ cell tumours to provide insight into their development and cell of origin, both of which are currently poorly understood.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-01T10:23:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003458","title":"TRACERx 100: RNAseq data from the first 100 TRACERx tumours","description":"TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC). This study looks at the multi-region RNAseq data from the TRACERx100 cohort with high enough quality RNA available. There is RNAseq data from 164 regions (64 patients).","abstract":"TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC). This study looks at the multi-region RNAseq data from the TRACERx100 cohort with high enough quality RNA available. There is RNAseq data from 164 regions (64 patients).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-01T11:51:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003459","title":"Profiling of SF188 ATRX isogenic glioma cells","description":"Paediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG) harbour frequent alterations in the SWI/SNF chromatin remodelling gene ATRX (α-thalassemia mental retardation X-linked), although the precise role of ATRX in tumorigenesis remains unclear. We sought to explore this using genomic analysis of patient samples, CRISPR-Cas9 engineered isogenic ATRX knockout (KO) pGBM cell lines and primary patient-derived cultures. ATRX loss of function resulted in a range of transcriptional changes linked to distinct epigenetic mechanisms. These included differential dysregulation of gene expression on the sex chromosomes, as well as loci associated with maternal imprinting. ATRX loss conferred reduced H3K9 trimethylation, and in turn an abrogated DNA repair capacity which resulted in stalled replication forks. Drug screening of isogenic and patient-derived cultures in vitro identified multiple chemotypes of PARP inhibitor to be differentially sensitive in ATRX-deficient cells, and to produce a pronounced radiosensitization related to a reduction of the ATM modulator APPL2. Using an in vivo orthotopic model of pGBM, treatment of ATRX-KO tumour-bearing mice with combined olaparib and radiation resulted in a significant prolongation of survival not observed in ATRX wild-type tumours. These data suggest a rational approach to target ATRX-deficient pGBM based upon the altered epigenetic control of the DNA damage response, and may represent a novel therapeutic strategy for these highly aggressive tumours.","abstract":"Paediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG) harbour frequent alterations in the SWI/SNF chromatin remodelling gene ATRX (α-thalassemia mental retardation X-linked), although the precise role of ATRX in tumorigenesis remains unclear. We sought to explore this using genomic analysis of patient samples, CRISPR-Cas9 engineered isogenic ATRX knockout (KO) pGBM cell lines and primary patient-derived cultures. ATRX loss of function resulted in a range of transcriptional changes linked to distinct epigenetic mechanisms. These included differential dysregulation of gene expression on the sex chromosomes, as well as loci associated with maternal imprinting. ATRX loss conferred reduced H3K9 trimethylation, and in turn an abrogated DNA repair capacity which resulted in stalled replication forks. Drug screening of isogenic and patient-derived cultures in vitro identified multiple chemotypes of PARP inhibitor to be differentially sensitive in ATRX-deficient cells, and to produce a pronounced radiosensitization related to a reduction of the ATM modulator APPL2. Using an in vivo orthotopic model of pGBM, treatment of ATRX-KO tumour-bearing mice with combined olaparib and radiation resulted in a significant prolongation of survival not observed in ATRX wild-type tumours. These data suggest a rational approach to target ATRX-deficient pGBM based upon the altered epigenetic control of the DNA damage response, and may represent a novel therapeutic strategy for these highly aggressive tumours.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003460","title":"GWAS and Meta-analysis on Frontal Fibrosing Alopecia in two European Populations","description":"Summary statistics of a GWAS meta-analysis for frontal fibrosing alopecia (FFA). A total of 7,039,930  genotyped and imputed variants were used for 1,044 European severe FFA cases and 4,145 matched population controls.","abstract":"Summary statistics of a GWAS meta-analysis for frontal fibrosing alopecia (FFA). A total of 7,039,930  genotyped and imputed variants were used for 1,044 European severe FFA cases and 4,145 matched population controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-05T10:09:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003461","title":"IBD_Whole_Exome_Sequencing","description":"to be updated","abstract":"to be updated","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003462","title":"Whole genome sequencing of 25 South African individuals with myasthenia gravis","description":"This study investigated the genetic basis of an ophthalmoplegic subphenotype of MG (OP-MG) which occurs in a proportion of myasthenics with juvenile symptom onset and African genetic ancestry. This OP-MG subphenotype is characterised by treatment resistant weakness of the extraocular muscles (EOMs) and the pathogenetic mechanism(s) underlying its development is unknown. The aim of this study was to use a hypothesis-generating genome-wide case-control analysis to identify candidate OP-MG susceptibility genes and pathways. Whole genome sequencing (WGS) was performed on 25 AChR-antibody positive myasthenic individuals of African genetic ancestry sampled from the phenotypic extremes: 15 with OP-MG (cases) and 10 individuals with control MG (EOM treatment-responsive).","abstract":"This study investigated the genetic basis of an ophthalmoplegic subphenotype of MG (OP-MG) which occurs in a proportion of myasthenics with juvenile symptom onset and African genetic ancestry. This OP-MG subphenotype is characterised by treatment resistant weakness of the extraocular muscles (EOMs) and the pathogenetic mechanism(s) underlying its development is unknown. The aim of this study was to use a hypothesis-generating genome-wide case-control analysis to identify candidate OP-MG susceptibility genes and pathways. Whole genome sequencing (WGS) was performed on 25 AChR-antibody positive myasthenic individuals of African genetic ancestry sampled from the phenotypic extremes: 15 with OP-MG (cases) and 10 individuals with control MG (EOM treatment-responsive).","study_type":"Other","pubmed_ids":[30881381],"external_links":null,"is_released":true,"released_date":"2019-02-07T09:42:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003463","title":"Exome sequencing of stroke cases with good or bad recovery three months after stroke","description":"With the aim to identify rare genetic variation involved in stroke recovery, this is a pilot study on extreme phenotypes of good and bad recovery. \nExome sequencing was performed on 41 and 49 samples in the bad and good recovery subset, respectively.  \nRare Variant association Analysis was performed on the exome sequencing results.","abstract":"With the aim to identify rare genetic variation involved in stroke recovery, this is a pilot study on extreme phenotypes of good and bad recovery. \nExome sequencing was performed on 41 and 49 samples in the bad and good recovery subset, respectively.  \nRare Variant association Analysis was performed on the exome sequencing results.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-08T09:27:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003464","title":"Examination_of_BCR_repertoire_of_tissue_resident_B_cells_in_non_lymphoid_organs","description":"In the human part of this study, perfused human kidneys and matched spleens (N=5) donated for transplantation but unsuitable for implantation were homogenized into single cell suspensions. These suspensions were then sorted for CD19+ cells, from which RNA was extracted for B cell receptor (BCR) sequencing. We aim to compare the B cell repertoire between matched kidney and spleen from each individual donor. In the mouse part of this study, we sorted separately intra- and extravascular B cells from mouse kidneys at a steady state and 6 weeks after resolution of induced urinary infection. Extracted RNA from these cell is then used for BCR sequencing and comparison of their immune repertoire.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"This project aims to understand the function of tissue-resident B cells in non-lymphoid mouse and human organs by examining their BCR repertoire and its changes after a local infection (RNA sequencing of sorted B cells will be performed at WTSI). In particular, it will clarify whether tissue-resident B cells in non-lymphoid are clonally expanded and whether their homing is antigen-specific.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003465","title":"Identification_of_immune_mechanisms_associated_with_the_high_rate_of_relapse_in_patient_with_visceral_leishmaniasis_and_HIV_co_infection","description":"RNA-seq transcriptomics of whole blood samples from longitudinal follow-up of a cohort of visceral leishmaniasis (VL) patients with and without HIV coinfection, from active disease through apparent cure and potential relapse. Analysis will identify potential correlates of relapse to identify immune mechanisms underlying the high rate of relapse in HIV/VL coinfection. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Identification of immune mechanisms associated with the high rate of\nrelapse in patient with visceral leishmaniasis and HIV co-infections","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-11T12:21:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003466","title":"G_T_Somatic_mutation_in_Primary_Sj_gren_s_Syndrome","description":"The overall objective is to test the hypothesis that PSS is caused by somatic mutation of immune regulatory or checkpoint genes in lymphoid cells.","abstract":"Autoimmune diseases affect 5% of the population and cause a wide range of painful disabilities that affect quality of life and may lead to life-threatening complications and early death.  In all these conditions, the immune system becomes hyperactive and damages tissues of the body including the joints, skin, mucous membranes, glands and vital organs.  In health, immune responses are closely regulated so that auto-immunity dose not occur.  Although research has identified many new ways to suppress auto-immunity, the reason why the immune system escapes from control in the first place, is completely unknown.\n\nThrough this research we are testing a new hypothesis that could explain why immune responses no longer respond to regulation in autoimmune disease.  Throughout life, tissues of the body accumulate genetic mutations due to random errors in copying the DNA when cells divide.  These mutations are known as 'somatic' mutations to indicate that they occur within an individual's lifetime and are not inherited from one generation to the next.  Somatic mutations are the cause of cancer and may play an important role in many chronic and age-related diseases.  Our research aims to test whether somatic mutations also cause autoimmunity.  The idea is that genes that control immune responses may become defective so that immune cells escape from normal regulatory signals.  There is evidence to support this idea from rare patients with inherited mutations that develop autoimmunity at a young age.  We also know that patients with autoimmunity, especially those with primary Sjogren's syndrome are at risk of developing lymphoma, a cancer of the immune system that involves exactly the same cells that cause autoimmunity.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003467","title":"Placental multi-omics data-mining in Intra-Uterine Growth Restriction","description":"Methylomics and transcriptomics array-based analysis of 36 placentas: 28 with IUGR (Intra-Uterine Growth Restriction) vs. 8 control pregnancies. Methylomics data were obtained using Illumina HumanMethylation-450k microarrays. Transcriptomics data were obtained using Illumina HumanHT-12 v4 Expression BeadChips.","abstract":"Methylomics and transcriptomics array-based analysis of 36 placentas: 28 with IUGR (Intra-Uterine Growth Restriction) vs. 8 control pregnancies. Methylomics data were obtained using Illumina HumanMethylation-450k microarrays. Transcriptomics data were obtained using Illumina HumanHT-12 v4 Expression BeadChips.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-11T15:25:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003468","title":"Adenoma to Carcinoma transition in Colorectal Cancer","description":"Although colorectal carcinoma development is well accepted as a step-wise and sequential process, it is commonly investigated using non-sequential adenoma and carcinoma samples. Here we compared molecular pathologies of the earliest carcinoma stages with those in their adenomatous precursors to unravel common and divergent genetic traits between matched neoplasms with a shared evolutionary history but different contemporary biology.","abstract":"Although colorectal carcinoma development is well accepted as a step-wise and sequential process, it is commonly investigated using non-sequential adenoma and carcinoma samples. Here we compared molecular pathologies of the earliest carcinoma stages with those in their adenomatous precursors to unravel common and divergent genetic traits between matched neoplasms with a shared evolutionary history but different contemporary biology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-12T11:12:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003469","title":"We evaluate the potential for routine WGS using ONT by sequencing the well-characterised reference sample NA12878 and the genome of an individual with ataxia-pancytopenia syndrome accompanied by severe immune dysregulation.","description":"Whole-genome sequencing (WGS) is becoming widely used in clinical medicine in diagnostic contexts and to inform treatment choice. While current sequencing technologies have been extremely successful, their reliance on short read lengths necessarily involves some limitations: accurately assaying certain genomic regions and classes of variation can be problematic. Recent advances in throughput and cost have made WGS using the Oxford Nanopore Technologies (ONT) MinION long-read single-molecule sequencer a potential solution to these challenges. Here we evaluate the potential for routine WGS using ONT by sequencing the well-characterised reference sample NA12878 and the genome of an individual with ataxia-pancytopenia syndrome accompanied by severe immune dysregulation, to 82× and 30× respectively. For NA12878, we evaluated single-nucleotide variant (SNV) calls based on data from multiple base-calling algorithms. We demonstrate that phasing metrics from a novel, reference panel-free, long-read-based method can improve variant-calling performance from otherwise modest levels, resulting in a false discovery rate of 7.1% and false negative rate of 8.5%; remaining errors are concentrated near homopolymers and in regions of reduced sequencing coverage. In the clinical sample, we are able to identify and directly phase two non-synonymous de novo variants in SAMD9L, (OMIM #159550) inferring that they both lie on a common paternal haplotype by overlap with parental genotypes at nearby common variants. This work demonstrates that methodological innovation can substantially reduce variant-calling error rates in ONT data, and that with on-going improvements in throughput, base-calling and dedicated long-read-based SNV-calling methodology, ONT offers promise as an option for clinical WGS.","abstract":"Whole-genome sequencing (WGS) is becoming widely used in clinical medicine in diagnostic contexts and to inform treatment choice. While current sequencing technologies have been extremely successful, their reliance on short read lengths necessarily involves some limitations: accurately assaying certain genomic regions and classes of variation can be problematic. Recent advances in throughput and cost have made WGS using the Oxford Nanopore Technologies (ONT) MinION long-read single-molecule sequencer a potential solution to these challenges. Here we evaluate the potential for routine WGS using ONT by sequencing the well-characterised reference sample NA12878 and the genome of an individual with ataxia-pancytopenia syndrome accompanied by severe immune dysregulation, to 82× and 30× respectively. For NA12878, we evaluated single-nucleotide variant (SNV) calls based on data from multiple base-calling algorithms. We demonstrate that phasing metrics from a novel, reference panel-free, long-read-based method can improve variant-calling performance from otherwise modest levels, resulting in a false discovery rate of 7.1% and false negative rate of 8.5%; remaining errors are concentrated near homopolymers and in regions of reduced sequencing coverage. In the clinical sample, we are able to identify and directly phase two non-synonymous de novo variants in SAMD9L, (OMIM #159550) inferring that they both lie on a common paternal haplotype by overlap with parental genotypes at nearby common variants. This work demonstrates that methodological innovation can substantially reduce variant-calling error rates in ONT data, and that with on-going improvements in throughput, base-calling and dedicated long-read-based SNV-calling methodology, ONT offers promise as an option for clinical WGS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-12T11:29:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003470","title":"Successful treatment of primary cutaneous diffuse large B cell lymphoma leg type with single agent venetoclax","description":"Primary cutaneous Diffuse Large B-cell Lymphoma leg type, (PCDLBCL-LT), accounts for 20% of all primary cutaneous B-lymphomas, predominantly involving the lower leg. Most PCDLBCL-LT exhibit activated B-cell (ABC) phenotype by histology and expression profiling, with high BCL-2, IRF4 and BCL6 expression, and constitutive NF-KB signalling in 69% of cases with poor prognosis. Here we present paired whole-exome sequencing of a R/R PCDLBCL-LT patient’s tumour to a median depth of 200X coverage (Illumina Hiseq4000), against a matched germline sample. Reads were mapped to genome build hg19 UCSC with BWA v0.7.16a. Duplicate reads were removed and QC performed with Picard v2.6.0. Variants were called with genome analysis toolkit v4 (GATK4) mutect2 caller to GATK best practice, and validated with a second variant caller Varscan v2. Provided are raw FASTQ files for re-analysis, processed BAM files, and unfiltered variant calling files generated for this study.","abstract":"Primary cutaneous Diffuse Large B-cell Lymphoma leg type, (PCDLBCL-LT), accounts for 20% of all primary cutaneous B-lymphomas, predominantly involving the lower leg. Most PCDLBCL-LT exhibit activated B-cell (ABC) phenotype by histology and expression profiling, with high BCL-2, IRF4 and BCL6 expression, and constitutive NF-KB signalling in 69% of cases with poor prognosis. Here we present paired whole-exome sequencing of a R/R PCDLBCL-LT patient’s tumour to a median depth of 200X coverage (Illumina Hiseq4000), against a matched germline sample. Reads were mapped to genome build hg19 UCSC with BWA v0.7.16a. Duplicate reads were removed and QC performed with Picard v2.6.0. Variants were called with genome analysis toolkit v4 (GATK4) mutect2 caller to GATK best practice, and validated with a second variant caller Varscan v2. Provided are raw FASTQ files for re-analysis, processed BAM files, and unfiltered variant calling files generated for this study.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003471","title":"Dedifferentiated_Melanoma","description":"De- and transdifferentiation of melanoma is a rare histopathological phenomenon that has not be characterised genetically. In this project we plan to sequence the genomes of de and transdifferentiated cases so as to define their genetic make-up.","abstract":"De- and transdifferentiation of melanoma is a rare histopathological phenomenon that has not be characterised genetically. In this project we plan to sequence the genomes of de and transdifferentiated cases so as to define their genetic make-up.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-13T10:50:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003472","title":"PID_Omenn","description":"Primary immunodeficiencies (PID) comprise a group of heterogenous disorders charaterised by heavily impaired immune system that often leads to life threatening infections. We are piloting scRNA-seq to characterise the immune system at higher resolution and assess the feasibilty of scRAN-seq as a diagnostic tool for improving treatment of these patients.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Primary immunodeficiencies (PID) comprise a group of heterogenous disorders charaterised by heavily impaired immune system that often leads to life threatening infections. We are piloting scRNA-seq to characterise the immune system at higher resolution and assess the feasibilty of scRAN-seq as a diagnostic tool for improving treatment of these patients.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003473","title":"Multivariate prediction of circulating tumor DNA fraction prior to sequencing in metastatic castration-resistant prostate cancer","description":null,"abstract":"Liquid biopsies based on plasma circulating tumor DNA (ctDNA) are seeing increasing adoption in precision oncology, but sensitivity is limited by the quantity of ctDNA in the bloodstream. We assembled a cohort of 472 plasma cell-free DNA (cfDNA) collections from men with progressing metastatic castration-resistant prostate cancer (mCRPC), each with a quantified ctDNA fraction and time-matched annotation of patient clinical characteristics. Clinical correlates of ctDNA fraction were identified and used to construct K-nearest neighbor- and gradient boosted trees-based predictive models. Model accuracy was evaluated using leave-one-out cross-validation. ctDNA was detected in 63% of samples at fractions between 2 - 89%. ctDNA fraction was strongly correlated with total cfDNA concentration, serum lactate dehydrogenase, alkaline phosphatase, and pattern of metastasis, but only weakly correlated with prostate specific antigen and hemoglobin. Lymphocyte count and body weight were non-informative. A model combining all informative variables predicted ctDNA fraction with an average error of 9.9%. Lines of prior systemic therapy had no independent effect on ctDNA fraction in patients with progressing disease, but ctDNA was reduced in patient plasma within one week after initiation of systemic therapy. We present an interactive website (http://ctdna.org) for predicting patient ctDNA fraction.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003474","title":"Exome sequencing of synchronous colorectal cancers","description":"Approximately 4% of colorectal cancer (CRC) patients have at least two simultaneous cancers in the colon. Due to the shared environment, these synchronous CRCs (SCRCs) provide a unique setting to study colorectal carcinogenesis. Understanding whether these tumors are genetically similar or distinct is essential when designing therapeutic approaches.\nWe performed exome sequencing of 47 primary cancers and corresponding normal samples from 23 patients. Additionally, we carried out a comprehensive mutational signature analysis to assess whether tumors had undergone similar mutational processes and the first immune cell score analysis (IS) of SCRC to analyze the interplay between immune cell invasion and mutation profile in both lesions of an individual.\nThe tumor pairs shared only few mutations, favoring different mutations in known CRC genes and signaling pathways, and displayed variation in their signature content. Two tumor pairs had discordant mismatch repair statuses. In majority of the pairs, IS varied between primaries. Differences were not explained by any clinicopathological variable or mutation burden.","abstract":"Approximately 4% of colorectal cancer (CRC) patients have at least two simultaneous cancers in the colon. Due to the shared environment, these synchronous CRCs (SCRCs) provide a unique setting to study colorectal carcinogenesis. Understanding whether these tumors are genetically similar or distinct is essential when designing therapeutic approaches.\nWe performed exome sequencing of 47 primary cancers and corresponding normal samples from 23 patients. Additionally, we carried out a comprehensive mutational signature analysis to assess whether tumors had undergone similar mutational processes and the first immune cell score analysis (IS) of SCRC to analyze the interplay between immune cell invasion and mutation profile in both lesions of an individual.\nThe tumor pairs shared only few mutations, favoring different mutations in known CRC genes and signaling pathways, and displayed variation in their signature content. Two tumor pairs had discordant mismatch repair statuses. In majority of the pairs, IS varied between primaries. Differences were not explained by any clinicopathological variable or mutation burden.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-14T08:09:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003475","title":"10X_Genomics_Comparison_","description":"10X Genomics Comparison","abstract":"10X Genomics Comparison","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003476","title":"DO NOT USE (DELETED)","description":"NO","abstract":"NO","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003477","title":"Lymph nodes and liver metastases of colorectal cancer","description":"This study described the route of lymph node and liver metastases in colorectal cancer patients.","abstract":"This study described the route of lymph node and liver metastases in colorectal cancer patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003478","title":"Phylogeography_transmission_dynamics_and_pathogenesis_of_bluetongue","description":"Phylogeography transmission dynamics and pathogenesis of bluetongue\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Phylogeography transmission dynamics and pathogenesis of bluetongue","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003479","title":"Single_cell_analysis_T_cell_activation","description":"We isolated naïve and memory T cells from healthy donors and cultured them in resting and stimulated conditions. We performed scRNA sequencing to assess T cell actiavtaion and perform sceQTL analysis.\n\nMajor challenges for translating GWAS variants to function include identification of the disease relevant cell types in which the associated variants function. We have shown that immune-disease variants are functional in CD4+ T cell activation, and understanding how GWAS variants affect the activation efficiency is critical for development of new therapies. To perform sceQTL analysis of naïve and memory T cell activation, here we stimulated T cells and profiled single cell transcriptome at different time points following stimulation. We mapped sceQTLs affecting cell activation. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We isolated naïve and memory T cells from healthy donors and cultured them in resting and stimulated conditions. We performed scRNA sequencing to assess T cell actiavtaion and perform sceQTL analysis.\n\nMajor challenges for translating GWAS variants to function include identification of the disease relevant cell types in which the associated variants function. We have shown that immune-disease variants are functional in CD4+ T cell activation, and understanding how GWAS variants affect the activation efficiency is critical for development of new therapies. To perform sceQTL analysis of naïve and memory T cell activation, here we stimulated T cells and profiled single cell transcriptome at different time points following stimulation. We mapped sceQTLs affecting cell activation. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-15T12:45:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003480","title":"Mutational patterns and regulatory networks in epigenetic subgroups of meningioma","description":null,"abstract":"DNA methylation patterns delineate clinically relevant subgroups of meningioma. We previously established the six meningioma methylation classes (MC) benign-1, 2, 3, intermediate-A, B and malignant.\n\nHere, we set out to identify subgroup-specific mutational patterns and pathway regulation. Whole-genome-sequencing was performed on 62 samples across all MCs and WHO grades from 62 patients with matched blood control, including 40 sporadic and 22 radiation-induced (Mrad) meningiomas. RNA sequencing was added for 18 cases and chromatin-immunoprecipitation for the enhancer mark H3K27ac followed by sequencing (ChIP-seq) for 16 samples.\n\nBesides the known mutations in meningioma, structural alterations were found to contribute to the spectrum of mechanisms inactivating NF2 in sporadic meningioma similar to previous reports for Mrad. Aberrations of DMD were found to be enriched in MCs with NF2 mutations and DMD was among the most differentially upregulated genes in NF2 mutant compared to NF2 wild-type cases. The mutational signature AC3 was detected in both sporadic meningioma and Mrad, but distributed across the genome in sporadic cases and enriched near genomic breakpoints in Mrad. In general, the malignant MC presented a significantly higher exposure to AC3 and higher genomic instability beyond the mutational load than the other MCs. Pathway analysis of the ChIP-seq clusters revealed that the FOXM1 is most differentially activated in high-grade cases, along with super enhancer recruitment near HOX genes and respective upregulation of expression.\n\nThis data further elucidate the biological mechanisms differentiating meningiomas of different WHO grade and epigenetic subgroups and suggest leveraging the genomic instability as novel therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003481","title":"Mutational patterns and regulatory networks in epigenetic subgroups of meningioma (H033)","description":"DNA methylation patterns delineate clinically relevant subgroups of meningioma. We previously established the six meningioma methylation classes (MC) benign-1, 2, 3, intermediate-A, B and malignant.\n\nHere, we set out to identify subgroup-specific mutational patterns and pathway regulation. Whole-genome-sequencing was performed on 62 samples across all MCs and WHO grades from 62 patients with matched blood control, including 40 sporadic and 22 radiation-induced (Mrad) meningiomas. RNA sequencing was added for 18 cases and chromatin-immunoprecipitation for the enhancer mark H3K27ac followed by sequencing (ChIP-seq) for 16 samples.\n\nBesides the known mutations in meningioma, structural alterations were found to contribute to the spectrum of mechanisms inactivating NF2 in sporadic meningioma similar to previous reports for Mrad. Aberrations of DMD were found to be enriched in MCs with NF2 mutations and DMD was among the most differentially upregulated genes in NF2 mutant compared to NF2 wild-type cases. The mutational signature AC3 was detected in both sporadic meningioma and Mrad, but distributed across the genome in sporadic cases and enriched near genomic breakpoints in Mrad. In general, the malignant MC presented a significantly higher exposure to AC3 and higher genomic instability beyond the mutational load than the other MCs. Pathway analysis of the ChIP-seq clusters revealed that the FOXM1 is most differentially activated in high-grade cases, along with super enhancer recruitment near HOX genes and respective upregulation of expression.\n\nThis data further elucidate the biological mechanisms differentiating meningiomas of different WHO grade and epigenetic subgroups and suggest leveraging the genomic instability as novel therapeutic targets.","abstract":"DNA methylation patterns delineate clinically relevant subgroups of meningioma. We previously established the six meningioma methylation classes (MC) benign-1, 2, 3, intermediate-A, B and malignant.\n\nHere, we set out to identify subgroup-specific mutational patterns and pathway regulation. Whole-genome-sequencing was performed on 62 samples across all MCs and WHO grades from 62 patients with matched blood control, including 40 sporadic and 22 radiation-induced (Mrad) meningiomas. RNA sequencing was added for 18 cases and chromatin-immunoprecipitation for the enhancer mark H3K27ac followed by sequencing (ChIP-seq) for 16 samples.\n\nBesides the known mutations in meningioma, structural alterations were found to contribute to the spectrum of mechanisms inactivating NF2 in sporadic meningioma similar to previous reports for Mrad. Aberrations of DMD were found to be enriched in MCs with NF2 mutations and DMD was among the most differentially upregulated genes in NF2 mutant compared to NF2 wild-type cases. The mutational signature AC3 was detected in both sporadic meningioma and Mrad, but distributed across the genome in sporadic cases and enriched near genomic breakpoints in Mrad. In general, the malignant MC presented a significantly higher exposure to AC3 and higher genomic instability beyond the mutational load than the other MCs. Pathway analysis of the ChIP-seq clusters revealed that the FOXM1 is most differentially activated in high-grade cases, along with super enhancer recruitment near HOX genes and respective upregulation of expression.\n\nThis data further elucidate the biological mechanisms differentiating meningiomas of different WHO grade and epigenetic subgroups and suggest leveraging the genomic instability as novel therapeutic targets.","study_type":"Other","pubmed_ids":[31069492],"external_links":null,"is_released":true,"released_date":"2019-02-15T15:49:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003482","title":"Dissecting features of epigenetic variants underlying cardiometabolic risk using full-resolution epigenome profiling in regulatory elements","description":null,"abstract":"Sparse profiling of CpG methylation in blood by microarrays have identified epigenetic links to common diseases. We apply methylC-capture sequencing (MCC-Seq) in a clinical population of ~200 adipose tissue and matched blood samples (Ntotal~400), providing high-resolution methylation profiling (&amp;gt;1.3M CpGs) at regulatory elements. We link methylation to cardiometabolic risk through associations to circulating plasma lipid levels and identify lipid-associated CpGs with unique localization patterns in regulatory elements. We show distinct features of tissue-specific versus tissue-independent lipid-linked regulatory regions by contrasting with parallel assessments in ~800 independent adipose tissue and blood samples from the general population. We follow-up on adipose-specific regulatory regions under (1) genetic and (2) epigenetic (environmental) regulation via integrational studies. Overall, the comprehensive sequencing of regulatory element methylomes reveals a rich landscape of functional variants linked genetically as well as epigenetically to plasma lipid traits.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003483","title":"Human_Immune_cell_atlas","description":"Human Immune Cell Atlas\n\nThis project aims to identify corresponding immune cells in blood and tissue and their altered function in inflammation.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Human Immune Cell Atlas\n\nThis project aims to identify corresponding immune cells in blood and tissue and their altered function in inflammation.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003484","title":"TRACERx 100: RRBS data from a subset of the first 100 TRACERx tumours","description":"TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC). This study looks at multi-region RRBS data from the TRACERx100 cohort selected for quantity of material available and high tumour purity. RRBS data was collected for 122 tumour regions across 36 patients each with matched normal. A subset of this cohort was used in a sister study looking at tumour neo-antigen promoter methylation status in NSCLC (71 tumour regions across 28 patients for a total of 99 samples).","abstract":"TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC). This study looks at multi-region RRBS data from the TRACERx100 cohort selected for quantity of material available and high tumour purity. RRBS data was collected for 122 tumour regions across 36 patients each with matched normal. A subset of this cohort was used in a sister study looking at tumour neo-antigen promoter methylation status in NSCLC (71 tumour regions across 28 patients for a total of 99 samples).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-18T12:08:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003485","title":"Chromatin 3D interactions mediate genetic effects on gene expression","description":"Studying the genetic basis of gene expression and chromatin organization is key to characterize the effect of genetic variability on the function and structure of the human genome. Here, we unravel how genetic variation perturbs gene regulation using a dataset combining activity of regulatory elements, gene expression and genetic variants across 317 individuals and two cell types.","abstract":"Studying the genetic basis of gene expression and chromatin organization is key to characterize the effect of genetic variability on the function and structure of the human genome. Here, we unravel how genetic variation perturbs gene regulation using a dataset combining activity of regulatory elements, gene expression and genetic variants across 317 individuals and two cell types.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001003486","title":"Mutational landscape of the transcriptome offers putative targets for immunotherapy of myeloproliferative neoplasms","description":"In this study, we aimed to comprehensively characterize in 113 myeloproliferative neoplasms (MPN) patients the mutational landscape of the granulocyte transcriptome using RNA sequencing data. We implemented workflows for fusion and variant calling, and differential splicing analysis for patients with hotspot SF3B1 mutations. Finally, we characterized the neoantigen landscape on individualized level taking each patient's HLA genotype (derived from the same RNA-seq dataset) into account.","abstract":"In this study, we aimed to comprehensively characterize in 113 myeloproliferative neoplasms (MPN) patients the mutational landscape of the granulocyte transcriptome using RNA sequencing data. We implemented workflows for fusion and variant calling, and differential splicing analysis for patients with hotspot SF3B1 mutations. Finally, we characterized the neoantigen landscape on individualized level taking each patient's HLA genotype (derived from the same RNA-seq dataset) into account.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-18T19:34:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003487","title":"Combined gene expression and digital pathology identifies molecular mediators of T cell exclusion and immune suppression in ovarian cancer","description":"Close proximity between cytotoxic T lymphocytes and tumour cells is required for effective immunotherapy. However, what determines the spatial distribution of T cells in the tumour microenvironment is not well understood. Coupling digital pathology and transcriptome analysis on a large ovarian tumour cohort, we develop a machine learning approach to molecularly classify and characterize tumour-immune phenotypes. Our study identifies two important hallmarks characterizing T cell excluded tumours: 1) loss of antigen presentation on tumour cells and 2) upregulation of TGFb and activated stroma. Furthermore, we identify TGFb as a key mediator of T cell exclusion. TGFb reduces MHC-I expression in ovarian cancer cells in vitro; TGFb also activates fibroblasts and induced extracellular matrix (ECM) production as a potential physical barrier to hinder T cell infiltration. Our findings indicate that targeting TGFb may represent a promising strategy to overcome T cell exclusion and improve clinical benefits of cancer immunotherapy.","abstract":"Close proximity between cytotoxic T lymphocytes and tumour cells is required for effective immunotherapy. However, what determines the spatial distribution of T cells in the tumour microenvironment is not well understood. Coupling digital pathology and transcriptome analysis on a large ovarian tumour cohort, we develop a machine learning approach to molecularly classify and characterize tumour-immune phenotypes. Our study identifies two important hallmarks characterizing T cell excluded tumours: 1) loss of antigen presentation on tumour cells and 2) upregulation of TGFb and activated stroma. Furthermore, we identify TGFb as a key mediator of T cell exclusion. TGFb reduces MHC-I expression in ovarian cancer cells in vitro; TGFb also activates fibroblasts and induced extracellular matrix (ECM) production as a potential physical barrier to hinder T cell infiltration. Our findings indicate that targeting TGFb may represent a promising strategy to overcome T cell exclusion and improve clinical benefits of cancer immunotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-20T00:20:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003488","title":"Growth Hormone (GH) -secreting Pituitary Adenoma","description":"We profiled the somatic landscape of 21 growth hormone (GH) -secreting pituitary adenomas using somatic copy-number alteration (SCNA), whole-genome sequencing (WGS), bisulfate sequencing, and transcriptome approaches. See details in Valimaki et al. Genetic and epigenetic characterization of growth hormone (GH) - secreting pituitary tumors. Manuscript in preparation, 2019.","abstract":"We profiled the somatic landscape of 21 growth hormone (GH) -secreting pituitary adenomas using somatic copy-number alteration (SCNA), whole-genome sequencing (WGS), bisulfate sequencing, and transcriptome approaches. See details in Valimaki et al. Genetic and epigenetic characterization of growth hormone (GH) - secreting pituitary tumors. Manuscript in preparation, 2019.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-20T08:00:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003489","title":"Molecular phenotyping of MCA/ID patients to improve diagnosis","description":"De novo structural variants are frequently identified in individuals with neurodevelopmental disorders, but the genes driving their phenotypes are often unknown. In this study we performed Whole Genome Sequencing, RNA-sequencing and ATAC-sequencing on samples of 51 patients with intellectual disability and/or multiple congenital anomalies and their biological parents (when available). The goals of the study were to gain more insights in the molecular consequences of (complex) genomic rearrangements and to improve the genetic diagnosis of patients carrying such rearrangements. Data is divided in four separate datasets based on type of source material and data access restrictions due to consent.","abstract":"De novo structural variants are frequently identified in individuals with neurodevelopmental disorders, but the genes driving their phenotypes are often unknown. In this study we performed Whole Genome Sequencing, RNA-sequencing and ATAC-sequencing on samples of 51 patients with intellectual disability and/or multiple congenital anomalies and their biological parents (when available). The goals of the study were to gain more insights in the molecular consequences of (complex) genomic rearrangements and to improve the genetic diagnosis of patients carrying such rearrangements. Data is divided in four separate datasets based on type of source material and data access restrictions due to consent.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-20T09:05:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003490","title":"Predicting brain tumor recurrence: development and validation of a DNA-methylation based nomogram in meningioma","description":"Our work is the first to demonstrate the transformative utility of integrating clinical and molecular factors for use beyond simple classification into the realm of individualized prognostication for any brain tumor. Using our developed and validated tools that are publicly available, clinicians will be able combine clinical and molecular factors to determine an individualized probability of recurrence for patients with meningiomas. This represents a major advance in the field of personalized medicine for neuro-oncology, and the use of this tool can help clinicians overcome one of the most challenging limitations we face when treating patients with meningiomas.","abstract":"Our work is the first to demonstrate the transformative utility of integrating clinical and molecular factors for use beyond simple classification into the realm of individualized prognostication for any brain tumor. Using our developed and validated tools that are publicly available, clinicians will be able combine clinical and molecular factors to determine an individualized probability of recurrence for patients with meningiomas. This represents a major advance in the field of personalized medicine for neuro-oncology, and the use of this tool can help clinicians overcome one of the most challenging limitations we face when treating patients with meningiomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-20T13:22:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003491","title":"Single_cell_analysis_of_T_cell_suppression","description":"We isolated naïve T cells, Tregs and monocytes from healthy donors and cultured them in different ratios. We performed scRNA sequencing to assess regulation of T cell activation and perform sceQTL analysis.\n\nT cell activation is tightly regulated by delivery of stimulatory signals through antigen presenting cells and suppressive capacity exerted by Tregs. We have isolated monocytes, naive T cells and Tregs from blood of healthy donors and co-culture them in the presence of anti-CD3 to provide the stimulus. Across 100 healthy individuals, we performed sceQTL analysis, which allowed us to correlate genotypes with the single-cell gene expression of activated cell types and deconvolute the genetic background of T cell activation and Treg suppression.     \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We isolated naïve T cells, Tregs and monocytes from healthy donors and cultured them in different ratios. We performed scRNA sequencing to assess regulation of T cell activation and perform sceQTL analysis.\n\nT cell activation is tightly regulated by delivery of stimulatory signals through antigen presenting cells and suppressive capacity exerted by Tregs. We have isolated monocytes, naive T cells and Tregs from blood of healthy donors and co-culture them in the presence of anti-CD3 to provide the stimulus. Across 100 healthy individuals, we performed sceQTL analysis, which allowed us to correlate genotypes with the single-cell gene expression of activated cell types and deconvolute the genetic background of T cell activation and Treg suppression.     \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003492","title":"HSC_population_dynamics__scRNA_seq___KX003","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003493","title":"High-resolution structural genomics reveals new therapeutic vulnerabilities in glioblastoma","description":"We investigated the role of 3D genome architecture in instructing functional properties of glioblastoma stem cells (GSCs) by generating the highest-resolution 3D genome maps to-date for this cancer. Integration of DNA contact maps with chromatin and transcriptional profiles identified specific mechanisms of gene regulation, including individual physical interactions between regulatory regions and their target genes. Residing in structurally conserved regions in GSCs was CD276, a gene known to play a role in immuno-modulation. We show that, unexpectedly, CD276 is part of a stemness network in GSCs and can be targeted with an antibody-drug conjugate to curb self-renewal, a key stemness property. Our results demonstrate that integrated structural genomics datasets can be employed to rationally identify therapeutic vulnerabilities in self-renewing cells.","abstract":"We investigated the role of 3D genome architecture in instructing functional properties of glioblastoma stem cells (GSCs) by generating the highest-resolution 3D genome maps to-date for this cancer. Integration of DNA contact maps with chromatin and transcriptional profiles identified specific mechanisms of gene regulation, including individual physical interactions between regulatory regions and their target genes. Residing in structurally conserved regions in GSCs was CD276, a gene known to play a role in immuno-modulation. We show that, unexpectedly, CD276 is part of a stemness network in GSCs and can be targeted with an antibody-drug conjugate to curb self-renewal, a key stemness property. Our results demonstrate that integrated structural genomics datasets can be employed to rationally identify therapeutic vulnerabilities in self-renewing cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-20T18:14:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003494","title":"RNAseq data of colon epithelia and cell lines.","description":null,"abstract":"RNAseq data from colon epithelia and cell lines.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003495","title":"Whole-exome sequencing data of intestinal epithelia and colitis-associated cancer.","description":null,"abstract":"Whole-exome sequencing data of intestinal epithelia and colitis-associated cancer","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003496","title":"Somatic mutations increase hepatic clonal fitness and regeneration in chronic liver disease","description":null,"abstract":"Normal tissues accumulate genetic changes, but it is unknown if mutations promote clonal expansion of normal cells in response to chronic injury. Exome sequencing of diseased liver samples from 83 patients revealed a complex mutational landscape in cirrhosis. Additional ultra-deep sequencing identified recurrent mutations in PKD1, PPARGC1B, KMT2D, and ARID1A. The number and size of mutant clones increased as a function of fibrosis stage and tissue damage. Also, chromosome 1 and 8 gains were observed, suggesting aneuploidy. To interrogate the functional impact of mutated genes, a pooled in vivo CRISPR screening approach was established. In agreement with sequencing results, examination of 147 genes again revealed that loss of Pkd1, Kmt2d, and Arid1a promoted clonal expansion. Conditional heterozygous deletion of these genes was also hepatoprotective in injury assays. Pre-malignant somatic alterations are often viewed through the lens of cancer, but we show that mutations can promote regeneration, likely independent of carcinogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-21T22:03:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003497","title":"Genomic stratification and liquid biopsy in a rare adrenocortical carcinoma (ACC) case, with dual lung metastases","description":"Adrenocortical carcinoma is a rare malignancy with a poor prognosis and few treatment options. Molecular characterization of this cancer remains limited. We present a case of an adrenocortical carcinoma (ACC) in a 37-yr-old female, with dual lung metastases identified 1 yr following commencement of adjuvant mitotane therapy. As standard therapeutic regimens are often unsuccessful in ACC, we undertook a comprehensive genomic study into this case to identify treatment options and monitor disease progress. We performed targeted and whole-genome sequencing of germline, primary tumor, and both metastatic tumors from this patient and monitored recurrence over 2 yr using liquid biopsy for ctDNA and steroid hormone measurements. Sequencing revealed the primary and metastatic tumors were hyperhaploid, with extensive loss of heterozygosity but few structural rearrangements. Loss-of-function mutations were identified in MSH2, TP53, RB1, and PTEN, resulting in tumors with mismatch repair signatures and microsatellite instability. At the cellular level, tumors were populated by mitochondria-rich oncocytes. Longitudinal ctDNA mutation and hormone profiles were unable to detect micrometastatic disease, consistent with clinical indicators of disease remission. The molecular signatures in our ACC case suggested immunotherapy in the event of disease progression; however, the patient remains free of cancer. The extensive molecular analysis presented here could be applied to other rare and/or poorly stratified cancers, to identify novel or repurpose existing therapeutic options, thereby broadly improving diagnoses, treatments, and prognoses.","abstract":"Adrenocortical carcinoma is a rare malignancy with a poor prognosis and few treatment options. Molecular characterization of this cancer remains limited. We present a case of an adrenocortical carcinoma (ACC) in a 37-yr-old female, with dual lung metastases identified 1 yr following commencement of adjuvant mitotane therapy. As standard therapeutic regimens are often unsuccessful in ACC, we undertook a comprehensive genomic study into this case to identify treatment options and monitor disease progress. We performed targeted and whole-genome sequencing of germline, primary tumor, and both metastatic tumors from this patient and monitored recurrence over 2 yr using liquid biopsy for ctDNA and steroid hormone measurements. Sequencing revealed the primary and metastatic tumors were hyperhaploid, with extensive loss of heterozygosity but few structural rearrangements. Loss-of-function mutations were identified in MSH2, TP53, RB1, and PTEN, resulting in tumors with mismatch repair signatures and microsatellite instability. At the cellular level, tumors were populated by mitochondria-rich oncocytes. Longitudinal ctDNA mutation and hormone profiles were unable to detect micrometastatic disease, consistent with clinical indicators of disease remission. The molecular signatures in our ACC case suggested immunotherapy in the event of disease progression; however, the patient remains free of cancer. The extensive molecular analysis presented here could be applied to other rare and/or poorly stratified cancers, to identify novel or repurpose existing therapeutic options, thereby broadly improving diagnoses, treatments, and prognoses.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-22T07:29:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003498","title":"DIME study: Safety, dose-response and efficacy of treatment with Anaerobutyricum soehgenii on glucose metabolism in human subjects with metabolic syndrome","description":"The intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We herefore performed a phase I/II dose-finding and safety study on the effect of oral intake of the anaerobic butyrogenic Anaerobutyricum soehgenii  on glucose metabolism in subjects with metabolic syndrome. We found that treatment with A. soehgenii was safe and observed an overall significant and dose-dependent increase in insulin sensitivity after 4 weeks in all treated subjects. This was accompanied by an altered microbiota composition and a change in bile acid metabolism. Finally, we show that metabolic response upon administration of A. soehgenii  (defined as improved insulin sensitivity 4 weeks after A. soehgenii  intake) is dependent on microbiota composition at baseline. These data in humans are promising and additional studies are needed to study long-term effects as well as modes of delivery.","abstract":"The intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We herefore performed a phase I/II dose-finding and safety study on the effect of oral intake of the anaerobic butyrogenic Anaerobutyricum soehgenii  on glucose metabolism in subjects with metabolic syndrome. We found that treatment with A. soehgenii was safe and observed an overall significant and dose-dependent increase in insulin sensitivity after 4 weeks in all treated subjects. This was accompanied by an altered microbiota composition and a change in bile acid metabolism. Finally, we show that metabolic response upon administration of A. soehgenii  (defined as improved insulin sensitivity 4 weeks after A. soehgenii  intake) is dependent on microbiota composition at baseline. These data in humans are promising and additional studies are needed to study long-term effects as well as modes of delivery.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-22T08:59:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003499","title":"EXCEED Study","description":"EXCEED is a longitudinal population-based cohort which facilitates investigation of genetic, environmental and lifestyle-related determinants of a broad range of diseases and of multiple morbidity through data collected at baseline and via electronic healthcare record linkage. Recruitment has taken place in Leicester, Leicestershire and Rutland since 2013 and is ongoing, with approximately 10,000 participants aged 30-69 to date. The population of Leicester is diverse and additional recruitment from the local South Asian community is ongoing.","abstract":"EXCEED is a longitudinal population-based cohort which facilitates investigation of genetic, environmental and lifestyle-related determinants of a broad range of diseases and of multiple morbidity through data collected at baseline and via electronic healthcare record linkage. Recruitment has taken place in Leicester, Leicestershire and Rutland since 2013 and is ongoing, with approximately 10,000 participants aged 30-69 to date. The population of Leicester is diverse and additional recruitment from the local South Asian community is ongoing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-24T19:32:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003500","title":"Whole-genome sequencing of Tibetans from China","description":"Whole-genome sequencing of 27 Tibetan individuals from China using the Illumina-B HiSeq X platform. These data are part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/.","abstract":"Whole-genome sequencing of 27 Tibetan individuals from China using the Illumina-B HiSeq X platform. These data are part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-25T12:16:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003501","title":"Chromatin_accessability_in_cytokine_induced_immune_cell_states","description":"We isolated T cells and monocotyes from healthy platelet donors and cultured them in resting and stimulated conditions with addition of a range of cytokines. We performed ATAC sequencing to assess the chromatin accessability in different cytokines treated  cells. These cellular profiles were used to map risk variants to the cytokine-induced cell states relevant for autoimmune diseases.","abstract":"Genome wide association studies of autoimmune disease have identified many risk loci implicated in T cell and macrophage activation, differentiation and function. However, most identified risk variants are outside protein coding genes and additionally their activity may only be expressed in specific cell subsets and under limited conditions. Given that the inflammation and and autoimmune tissue distruction is driven by the local production of cytokines, we investigated cytokine induced changes in T cell and macrophage responses by using a combination of immunological and genomics approaches. We assessed the chromatin, transcriptional and proteomic signatures specific for each of the cytokine polarising conditions. These cellular profiles were used to map risk variants to the cytokine-induced cell states relevant for autoimmune diseases.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-26T13:52:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003502","title":"MutWP5__CRUK_Mutographs_of_Cancer__Lung__PD43291_Novaseq__WG_","description":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from lung tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will deeply sample from individuals with smoking-related lung diseases (COPD, pulmonary fibrosis, lung cancer) and those without smoking history. This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from lung tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will deeply sample from individuals with smoking-related lung diseases (COPD, pulmonary fibrosis, lung cancer) and those without smoking history. This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-26T16:10:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003503","title":"MutWP5__CRUK_Mutographs_of_Cancer__Lung__PD43291_Novaseq__Exome_","description":"Sequencing of LCM-derived microbiopsies from explanted lung from COPD patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutaiton burden in different portions of the lung. Whole-genome sequencing will be conducted on samples identified as promising from the initial targeted data. Results from this poriton of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from lung tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will deeply sample from individuals with smoking-related lung diseases (COPD, pulmonary fibrosis, lung cancer) and those without smoking history. This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-26T16:12:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003504","title":"Epiclomal: probabilistic clustering of sparse single-cell DNA methylation data","description":"We present Epiclomal, a probabilistic clustering method arising from a hierarchical mixture model to simultaneously cluster sparse single-cell DNA methylation data and infer their corresponding hidden methylation profiles. Using synthetic and published single-cell CpG datasets we show that Epiclomal outperforms non-probabilistic methods and is able to handle the inherent missing data feature which dominates single-cell CpG genome sequences. Using a recently published single-cell 5mCpG sequencing method (PBAL), we show that Epiclomal discovers sub-clonal patterns of methylation in aneuploid tumour genomes, thus defining epiclones. We show that epiclones may transcend copy number determined clonal lineages, thus opening this important form of clonal analysis in cancer.","abstract":"We present Epiclomal, a probabilistic clustering method arising from a hierarchical mixture model to simultaneously cluster sparse single-cell DNA methylation data and infer their corresponding hidden methylation profiles. Using synthetic and published single-cell CpG datasets we show that Epiclomal outperforms non-probabilistic methods and is able to handle the inherent missing data feature which dominates single-cell CpG genome sequences. Using a recently published single-cell 5mCpG sequencing method (PBAL), we show that Epiclomal discovers sub-clonal patterns of methylation in aneuploid tumour genomes, thus defining epiclones. We show that epiclones may transcend copy number determined clonal lineages, thus opening this important form of clonal analysis in cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-27T00:18:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003505","title":"RNA expression analysis of high vs low calcium treated primary human keratinocytes grown in monolayer.","description":"RNA expression analysis of high vs low calcium treated primary human keratinocytes grown in monolayer.","abstract":"RNA expression analysis of high vs low calcium treated primary human keratinocytes grown in monolayer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003506","title":"Analysis of Multiparametric MR imaging and tumor tissue sampling to identify response and acquired resistance to HIF-2 inhibition in patients with advanced clear cell renal cell carcinoma enrolled in a phase 1, multiple-dose, dose-escalation trial of PT2385, a HIF-2alpha inhibitor","description":null,"abstract":"Background: We investigated whether multiparametric magnetic resonance imaging (mpMRI) could identify activity of PT2385, a novel inhibitor of hypoxia inducible factor-2 (HIF-2), in patients with advanced clear cell renal cell carcinoma (ccRCC). Through tumor biopsies, we sought to identify mechanisms of response and resistance to HIF-2 inhibition.\nMethods: We enrolled patients treated on a multicenter phase I trial of PT2385 at our institution to a companion study investigating three mpMRI techniques, arterial spin labeling (ASL), dynamic contrast enhancement (DCE), and diffusion-weighted imaging (DWI), as potential markers of HIF-2 inhibition. Eligible subjects undergoing mpMRI had eGFR ≥30 mL/min/1.73m2. Subjects who were not eligible to undergo MRI could still undergo blood collection and optional tumor biopsies. The primary objective was to study mpMRI as a potential pharmacodynamic biomarker of response and resistance to PT2385. Secondary objectives were to identify potential blood and tumor biomarkers of response and resistance to PT2385.\nFindings: Between August 31, 2015 and November 30, 2015, we consented 11 patients. 10 were treated on the phase I trial, 7 underwent mpMRI, and 6 underwent tumor biopsies. Decrease in ASL perfusion was observed at 2 weeks on treatment with PT2385 in 14/16 lesions (87.5%) across 7 patients. Proximity ligations assay analysis showed dissociation of HIF-2 and HIF-1 following PT2385 treatment in 3/3 patients who underwent serial biopsies. In a patient with prolonged disease control and focal tumor growth, we discovered a HIF-2alpha gatekeeper mutation (G323E) resulting in preserved HIF-2 complexes and sustained HIF-2 target gene expression despite ongoing PT2385 treatment. \nInterpretation: ASL mpMRI warrants further exploration as an imaging biomarker for HIF-2 inhibition in patients with ccRCC. By combining tumorgraft models and clinical samples, we validated HIF-2 as a target and provide insight into mechanisms of resistance in human subjects.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-27T21:43:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003507","title":"Fixation effects on variant-calling in a clinical resequencing panel","description":"Formalin fixation is the standard method for preservation of tissue for diagnostic purposes, including pathological review and molecular assays. However, this method is known to cause artifacts that can affect the accuracy of molecular genetic tests. We assessed the applicability of alternative fixatives to determine whether these perform significantly better on next-generation sequencing assays, and whether adequate morphology is retained for primary diagnosis, in a prospective study using a clinical-grade laboratory-developed targeted resequencing assay. We examined and quantified several parameters relating to sequencing quality and variant-calling from tumor and normal colon epithelial tissues. We identify one alterative fixative, Sakura Universal Molecular Fixative that suppresses many formalin-related artifacts while retaining adequate morphology for pathological review.","abstract":"Formalin fixation is the standard method for preservation of tissue for diagnostic purposes, including pathological review and molecular assays. However, this method is known to cause artifacts that can affect the accuracy of molecular genetic tests. We assessed the applicability of alternative fixatives to determine whether these perform significantly better on next-generation sequencing assays, and whether adequate morphology is retained for primary diagnosis, in a prospective study using a clinical-grade laboratory-developed targeted resequencing assay. We examined and quantified several parameters relating to sequencing quality and variant-calling from tumor and normal colon epithelial tissues. We identify one alterative fixative, Sakura Universal Molecular Fixative that suppresses many formalin-related artifacts while retaining adequate morphology for pathological review.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-02-28T01:07:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003508","title":"300-Obese: clinical cohort of obese individuals, Nijmegen, the Netherlands","description":"300-Obese cohort was recruited at the Radboud University Medical Center (RUMC), Nijmegen, the Netherlands. The cohort comprises 377 participants included by the following criteria: age&gt;55 years, BMI&gt;27 kg/m2. The cohort data includes gut microbiome, NMR serum metabolomics, deep cardiovascular phenotyping and broad range of phenotypic information.","abstract":"300-Obese cohort was recruited at the Radboud University Medical Center (RUMC), Nijmegen, the Netherlands. The cohort comprises 377 participants included by the following criteria: age&gt;55 years, BMI&gt;27 kg/m2. The cohort data includes gut microbiome, NMR serum metabolomics, deep cardiovascular phenotyping and broad range of phenotypic information.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-01T12:19:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003509","title":"Clonal evolution in non-small cell lung cancer selects for copy number gains of MCL-1 that can be exploited therapeutically (HIPO-021)","description":"The critical role of mutated KRAS has been well-established in lung cancer. However, the inhibition of essential survival pathways in KRAS-mutated tumors remains ineffective. Here we explored non-oncogene addictions in non-small cell lung cancer by studying the clonal evolution of genes securing the continued survival of cancer cells. We identified subclonal copy-number gains of MCL-1 with high frequency in non-small cell lung cancer implying that the continued protection against cell death represents a critical prerequisite during tumor evolution. Using gene-targeted mouse models, we found that the sustained survival of cancer cells was dependent on MCL-1 even in the presence of alternative pro-survival BCL-2 members. KrasG12D-driven pulmonary adenocarcinoma development in mice required MCL-1 for optimal survival. Whereas the dependency on MCL-1 during tumor initiation was overcome by the additional loss of p53, pharmacologic targeting of MCL-1 in fully-established cancers was able to delay progression even when p53 was deleted. An altered immune cell repertoire in Mcl-1-deficient tumors indicated a STAT3-dependent resistance mechanisms and provided evidence that MCL-1-controlled cell death had immunogenic potential. In summary, we showed that MCL-1 amplifications in human non-small cell lung cancer represent a frequent genomic event during tumor evolution that protected cancer cells during tumor progression and thereby exemplifies a rational therapeutic target.","abstract":"The critical role of mutated KRAS has been well-established in lung cancer. However, the inhibition of essential survival pathways in KRAS-mutated tumors remains ineffective. Here we explored non-oncogene addictions in non-small cell lung cancer by studying the clonal evolution of genes securing the continued survival of cancer cells. We identified subclonal copy-number gains of MCL-1 with high frequency in non-small cell lung cancer implying that the continued protection against cell death represents a critical prerequisite during tumor evolution. Using gene-targeted mouse models, we found that the sustained survival of cancer cells was dependent on MCL-1 even in the presence of alternative pro-survival BCL-2 members. KrasG12D-driven pulmonary adenocarcinoma development in mice required MCL-1 for optimal survival. Whereas the dependency on MCL-1 during tumor initiation was overcome by the additional loss of p53, pharmacologic targeting of MCL-1 in fully-established cancers was able to delay progression even when p53 was deleted. An altered immune cell repertoire in Mcl-1-deficient tumors indicated a STAT3-dependent resistance mechanisms and provided evidence that MCL-1-controlled cell death had immunogenic potential. In summary, we showed that MCL-1 amplifications in human non-small cell lung cancer represent a frequent genomic event during tumor evolution that protected cancer cells during tumor progression and thereby exemplifies a rational therapeutic target.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003510","title":"Juvenile Idiopathic Arthritis exome sequencing in a consanguineous family","description":"Identify the causative gene defect in three affected patients with JIA.","abstract":"Identify the causative gene defect in three affected patients with JIA.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-03T22:06:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003511","title":"The Medical Genome Reference Bank: a whole genome data resource of 4,000 healthy elderly individuals.","description":"Allele frequency data from human reference populations is of increasing value for filtering and assignment of pathogenicity to genetic variants. Aged and healthy populations are more likely to be selectively depleted of pathogenic alleles, and therefore particularly suitable as a reference populations for the major diseases of clinical and public health importance. However, reference studies of the healthy elderly have remained under represented in human genetics. We have developed the Medical Genome Reference Bank (MGRB), a large scale comprehensive whole genome dataset of confirmed healthy elderly individuals, to provide a publicly accessible resource for health related research, and for clinical genetics. It also represents a useful resource for studying the genetics of healthy aging. The MGRB comprises 4,000 healthy, older individuals with no reported history of cancer, cardiovascular disease or dementia, recruited from two Australian community based cohorts. DNA derived from blood samples will be subject to whole genome sequencing. The MGRB will measure genome wide genetic variation in 4,000 individuals, mostly of European decent, aged 60 to 95 years (mean age 75 years). The MGRB has committed to a policy of data sharing, employing a hierarchical data management system to maintain participant privacy and confidentiality, whilst maximizing research and clinical usage of the database. The MGRB will represent a dataset of international significance, broadly accessible to the clinical and genetic research community.","abstract":"Allele frequency data from human reference populations is of increasing value for filtering and assignment of pathogenicity to genetic variants. Aged and healthy populations are more likely to be selectively depleted of pathogenic alleles, and therefore particularly suitable as a reference populations for the major diseases of clinical and public health importance. However, reference studies of the healthy elderly have remained under represented in human genetics. We have developed the Medical Genome Reference Bank (MGRB), a large scale comprehensive whole genome dataset of confirmed healthy elderly individuals, to provide a publicly accessible resource for health related research, and for clinical genetics. It also represents a useful resource for studying the genetics of healthy aging. The MGRB comprises 4,000 healthy, older individuals with no reported history of cancer, cardiovascular disease or dementia, recruited from two Australian community based cohorts. DNA derived from blood samples will be subject to whole genome sequencing. The MGRB will measure genome wide genetic variation in 4,000 individuals, mostly of European decent, aged 60 to 95 years (mean age 75 years). The MGRB has committed to a policy of data sharing, employing a hierarchical data management system to maintain participant privacy and confidentiality, whilst maximizing research and clinical usage of the database. The MGRB will represent a dataset of international significance, broadly accessible to the clinical and genetic research community.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-04T04:03:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003512","title":"whole-genome sequencing of gastric cancer","description":"Gastric cancer is one of the most common cancers. Genome-wide analysis of genomic signatures might reveal novel mechanisms for gastric cancer tumorigenesis. Here, we analyzed structural variations and mutational signatures via whole-genome sequencing of 168 gastric cancer samples. Our data demonstrates diverse models of complex structural variations operative in GC, which lead to high-level amplification of oncogenes.","abstract":"Gastric cancer is one of the most common cancers. Genome-wide analysis of genomic signatures might reveal novel mechanisms for gastric cancer tumorigenesis. Here, we analyzed structural variations and mutational signatures via whole-genome sequencing of 168 gastric cancer samples. Our data demonstrates diverse models of complex structural variations operative in GC, which lead to high-level amplification of oncogenes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-04T10:26:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003513","title":"Comparison of 3 protocols for deriving pancreatic progenitors from hPSC with RNA-seq and ATAC-seq","description":"Several distinct differentiation protocols for deriving pancreatic progenitors (PP) from human pluripotent stem cells have been described but it remains to be shown how similar the PP are across protocols, and how well they resemble their in vivo counterparts. Here we evaluated three differentiation protocols; performed RNA and ATAC-seq on isolated PP derived with these, and compared them to fetal human pancreas populations. This enabled us to define a shared transcriptional and epigenomic signature of the PP, including several genes not previously implicated in pancreas development. Furthermore, we identified a significant and previously unappreciated cross-protocol variation of the PP through multi-omics analysis and demonstrate how such information can be applied to refine differentiation protocols for derivation of insulin-producing beta-like cells. Together, our study highlights the importance of a detailed characterization of defined cell populations derived from distinct differentiation protocols, and provides a valuable resource for exploring human pancreatic development.","abstract":"Several distinct differentiation protocols for deriving pancreatic progenitors (PP) from human pluripotent stem cells have been described but it remains to be shown how similar the PP are across protocols, and how well they resemble their in vivo counterparts. Here we evaluated three differentiation protocols; performed RNA and ATAC-seq on isolated PP derived with these, and compared them to fetal human pancreas populations. This enabled us to define a shared transcriptional and epigenomic signature of the PP, including several genes not previously implicated in pancreas development. Furthermore, we identified a significant and previously unappreciated cross-protocol variation of the PP through multi-omics analysis and demonstrate how such information can be applied to refine differentiation protocols for derivation of insulin-producing beta-like cells. Together, our study highlights the importance of a detailed characterization of defined cell populations derived from distinct differentiation protocols, and provides a valuable resource for exploring human pancreatic development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-04T10:37:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003514","title":"The biology of cell-free DNA fragmentation and the roles ofDNASE1, DNASE1L3 and DFFB","description":"The biology of cell-free DNA fragmentation and the roles of\nDNASE1, DNASE1L3 and DFFB","abstract":"The biology of cell-free DNA fragmentation and the roles of\nDNASE1, DNASE1L3 and DFFB","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-05T08:48:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003515","title":"Gene regulation of human stimulated and cultured CD4+ Treg cells","description":"This dataset maps gene expression regulation in human primary regulatory CD4+ T cells (Tregs) stimulated using PMA and ionomycin or cultured without stimulus for 18 hours. It includes whole genome sequence data for ChM-seq (18 H3K4me3, 20 H3K27ac and 3 inputs), ATAC-seq (42 samples) and whole transcriptome (39 samples). All individuals were genotyped using coreExome Illumina SNP chip array (included in EGAS00001003516).","abstract":"This dataset maps gene expression regulation in human primary regulatory CD4+ T cells (Tregs) stimulated using PMA and ionomycin or cultured without stimulus for 18 hours. It includes whole genome sequence data for ChM-seq (18 H3K4me3, 20 H3K27ac and 3 inputs), ATAC-seq (42 samples) and whole transcriptome (39 samples). All individuals were genotyped using coreExome Illumina SNP chip array (included in EGAS00001003516).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-05T09:27:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003516","title":"Gene_regulation_of_human_CD4__Treg_cells_","description":"This dataset maps gene expression regulation in human primary regulatory CD4+ T cells (Tregs). It includes whole genome sequence data for ChM-seq (118 H3K4me3, 118 H3K27ac and 6 inputs), ATAC-seq (114 samples) and whole transcriptome (141 samples). All individuals were genotyped (130 samples) using coreExome Illumina SNP chip array. The final quality filtered set included 123 individuals with RNA-seq data, 73 with ATAC-seq, 91 with H3K27ac ChM-seq and 88 with H3K4me3 ChM-seq data. A total of 62 individuals had QCed data for all the assays.","abstract":"This dataset maps gene expression regulation in human primary regulatory CD4+ T cells (Tregs). It includes whole genome sequence data for ChM-seq (118 H3K4me3, 118 H3K27ac and 6 inputs), ATAC-seq (114 samples) and whole transcriptome (141 samples). All individuals were genotyped (130 samples) using coreExome Illumina SNP chip array. The final quality filtered set included 123 individuals with RNA-seq data, 73 with ATAC-seq, 91 with H3K27ac ChM-seq and 88 with H3K4me3 ChM-seq data. A total of 62 individuals had QCed data for all the assays.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-05T09:27:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003517","title":"Understanding_the_multicellular_dynamics_of_clear_cell_renal_cell_carcinoma___DNA_sequencing","description":"This study will reconstruct the single cellular phylogeny of tumour and immune cells in relation to both genomic, functional, and spatial location. 20 tumours in total will be studied, including non-progressing small renal masses, progressing small renal masses, relatively indolent larger tumours, and high risk tumour with metastatic sampling. We aim to:\n\nGenerate a focused, comprehensive phylogenetic characterisation of tumour cells\nUnderstand the dependencies of the cancer genome, transcriptome, tissue architecture and the single cellular micro-environment\nQuantify the single cellular composition and functional intra- and inter- tumoural heterogeneity\nDetermine the phylogeny of tumour associated lymphocytes and their relationship to neo-epitopes and the immune microenvironment\nInvestigate the mechanisms by which the tumour-normal interface constrains tumoural growth","abstract":"This study will reconstruct the single cellular phylogeny of tumour and immune cells in relation to both genomic, functional, and spatial location. 20 tumours in total will be studied, including non-progressing small renal masses, progressing small renal masses, relatively indolent larger tumours, and high risk tumour with metastatic sampling. We aim to:\n\nGenerate a focused, comprehensive phylogenetic characterisation of tumour cells\nUnderstand the dependencies of the cancer genome, transcriptome, tissue architecture and the single cellular micro-environment\nQuantify the single cellular composition and functional intra- and inter- tumoural heterogeneity\nDetermine the phylogeny of tumour associated lymphocytes and their relationship to neo-epitopes and the immune microenvironment\nInvestigate the mechanisms by which the tumour-normal interface constrains tumoural growth","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-07T09:16:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003518","title":"Understanding_the_multicellular_dynamics_of_clear_cell_renal_cell_carcinoma___bulk_RNA_sequencing","description":"This study will reconstruct the single cellular phylogeny of tumour and immune cells in relation to both genomic, functional, and spatial location. 20 tumours in total will be studied, including non-progressing small renal masses, progressing small renal masses, relatively indolent larger tumours, and high risk tumour with metastatic sampling. We aim to:\n\nGenerate a focused, comprehensive phylogenetic characterisation of tumour cells\nUnderstand the dependencies of the cancer genome, transcriptome, tissue architecture and the single cellular micro-environment\nQuantify the single cellular composition and functional intra- and inter- tumoural heterogeneity\nDetermine the phylogeny of tumour associated lymphocytes and their relationship to neo-epitopes and the immune microenvironment\nInvestigate the mechanisms by which the tumour-normal interface constrains tumoural growth","abstract":"This study will reconstruct the single cellular phylogeny of tumour and immune cells in relation to both genomic, functional, and spatial location. 20 tumours in total will be studied, including non-progressing small renal masses, progressing small renal masses, relatively indolent larger tumours, and high risk tumour with metastatic sampling. We aim to:\n\nGenerate a focused, comprehensive phylogenetic characterisation of tumour cells\nUnderstand the dependencies of the cancer genome, transcriptome, tissue architecture and the single cellular micro-environment\nQuantify the single cellular composition and functional intra- and inter- tumoural heterogeneity\nDetermine the phylogeny of tumour associated lymphocytes and their relationship to neo-epitopes and the immune microenvironment\nInvestigate the mechanisms by which the tumour-normal interface constrains tumoural growth","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003519","title":"Understanding_the_multicellular_dynamics_of_clear_cell_renal_cell_carcinoma___single_cell_RNA_sequencing","description":"This study will reconstruct the single cellular phylogeny of tumour and immune cells in relation to both genomic, functional, and spatial location. 20 tumours in total will be studied, including non-progressing small renal masses, progressing small renal masses, relatively indolent larger tumours, and high risk tumour with metastatic sampling. We aim to:\n\nGenerate a focused, comprehensive phylogenetic characterisation of tumour cells\nUnderstand the dependencies of the cancer genome, transcriptome, tissue architecture and the single cellular micro-environment\nQuantify the single cellular composition and functional intra- and inter- tumoural heterogeneity\nDetermine the phylogeny of tumour associated lymphocytes and their relationship to neo-epitopes and the immune microenvironment\nInvestigate the mechanisms by which the tumour-normal interface constrains tumoural growth","abstract":"This study will reconstruct the single cellular phylogeny of tumour and immune cells in relation to both genomic, functional, and spatial location. 20 tumours in total will be studied, including non-progressing small renal masses, progressing small renal masses, relatively indolent larger tumours, and high risk tumour with metastatic sampling. We aim to:\n\nGenerate a focused, comprehensive phylogenetic characterisation of tumour cells\nUnderstand the dependencies of the cancer genome, transcriptome, tissue architecture and the single cellular micro-environment\nQuantify the single cellular composition and functional intra- and inter- tumoural heterogeneity\nDetermine the phylogeny of tumour associated lymphocytes and their relationship to neo-epitopes and the immune microenvironment\nInvestigate the mechanisms by which the tumour-normal interface constrains tumoural growth","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-07T09:35:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003520","title":"MutWP4__CRUK_Grand_Challenge_Mutographs_of_Cancer__Pancreatic_Organoids","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, Kings College London will characterise the mutational signatures induced by putative human carcinogens in order to identify the origins of mutational signatures found in human cancers. To achieve this human organoid cell cultures will be exposed to a representative catalogue of known or suspected human carcinogens and mutagens and, using whole genome sequencing, the patterns of mutations induced by them will be determined. Somatic mutational signatures will be subsequently extracted by non-negative matrix factorisation methods and correlated with exposure data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, Kings College London will characterise the mutational signatures induced by putative human carcinogens in order to identify the origins of mutational signatures found in human cancers. To achieve this human organoid cell cultures will be exposed to a representative catalogue of known or suspected human carcinogens and mutagens and, using whole genome sequencing, the patterns of mutations induced by them will be determined. Somatic mutational signatures will be subsequently extracted by non-negative matrix factorisation methods and correlated with exposure data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-08T14:19:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003521","title":"Expanding the neurodevelopmental phenotypes of individuals with de novo KMT2A variants","description":"De novo loss-of-function (LoF) variants in the KMT2A gene are associated with Wiedemann-Steiner Syndrome (WSS). Recently, de novo KMT2A variants have been identified in sequencing studies of cohorts of individuals with neurodevelopmental disorders (NDDs). However, most of these studies lack the detailed clinical information required to determine whether those individuals have isolated NDDs or WSS (i.e. syndromic NDDs). We performed thorough clinical and neurodevelopmental phenotyping on six individuals with de novo KMT2A variants. From these data, we found that all six patients met clinical criteria for WSS and we further define the neurodevelopmental phenotypes associated with KMT2A variants and WSS. In particular, we identified a subtype of Autism Spectrum Disorder (ASD) in five individuals, characterized by marked rigid, repetitive and inflexible behaviours, emotional dysregulation, externalizing behaviours, but relative social motivation. To further explore the clinical spectrum associated with KMT2A variants, we also conducted a meta-analysis of individuals with KMT2A variants reported in the published literature. We found that de novo LoF or missense variants in KMT2A were significantly more prevalent than predicted by a previously established statistical model of de novo mutation rate for KMT2A. Our genotype-phenotype findings better define the clinical spectrum associated with KMT2A variants and suggest that individuals with de novo LoF and missense variants likely have a clinically unrecognized diagnosis of WSS, rather than isolated NDD or ASD alone. This highlights the importance of a clinical genetic and neurodevelopmental assessment for individuals with such variants in KMT2A.","abstract":"De novo loss-of-function (LoF) variants in the KMT2A gene are associated with Wiedemann-Steiner Syndrome (WSS). Recently, de novo KMT2A variants have been identified in sequencing studies of cohorts of individuals with neurodevelopmental disorders (NDDs). However, most of these studies lack the detailed clinical information required to determine whether those individuals have isolated NDDs or WSS (i.e. syndromic NDDs). We performed thorough clinical and neurodevelopmental phenotyping on six individuals with de novo KMT2A variants. From these data, we found that all six patients met clinical criteria for WSS and we further define the neurodevelopmental phenotypes associated with KMT2A variants and WSS. In particular, we identified a subtype of Autism Spectrum Disorder (ASD) in five individuals, characterized by marked rigid, repetitive and inflexible behaviours, emotional dysregulation, externalizing behaviours, but relative social motivation. To further explore the clinical spectrum associated with KMT2A variants, we also conducted a meta-analysis of individuals with KMT2A variants reported in the published literature. We found that de novo LoF or missense variants in KMT2A were significantly more prevalent than predicted by a previously established statistical model of de novo mutation rate for KMT2A. Our genotype-phenotype findings better define the clinical spectrum associated with KMT2A variants and suggest that individuals with de novo LoF and missense variants likely have a clinically unrecognized diagnosis of WSS, rather than isolated NDD or ASD alone. This highlights the importance of a clinical genetic and neurodevelopmental assessment for individuals with such variants in KMT2A.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-09T03:52:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003522","title":"Gene_regulation_of_human_CD4__Treg_cells_","description":"Recently, we identified that immune disease associated variants are enriched in active promoters (marked by H3K4me3 modification) specific to CD4+ T lymphocytes, especially in regulatory T cells (Tregs). This enrichment suggests that a proportion of associated variants is likely to confer disease risk by modulating gene-expression in CD4-positive subsets of T cells. Here, we aim to further study the effects of disease associated variants - specifically we want to assess if different alleles can lead to imbalanced histone modification levels, differences in chromatin open regions and altered gene expression. We will perform RNA-seq, ATAC-seq and ChIP-seq on Tcells isolated from 100 healthy blood donors. All individuals will be also genotyped using a genome-wide array. We want to focus on the regulatory T cells in the first instance but also extend the analyses to other relevant CD4-positive subtypes where relevant.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Recently, we identified that immune disease associated variants are enriched in active promoters (marked by H3K4me3 modification) specific to CD4+ T lymphocytes, especially in regulatory T cells (Tregs). This enrichment suggests that a proportion of associated variants is likely to confer disease risk by modulating gene-expression in CD4-positive subsets of T cells. Here, we aim to further study the effects of disease associated variants - specifically we want to assess if different alleles can lead to imbalanced histone modification levels, differences in chromatin open regions and altered gene expression. We will perform RNA-seq, ATAC-seq and ChIP-seq on Tcells isolated from 100 healthy blood donors. All individuals will be also genotyped using a genome-wide array. We want to focus on the regulatory T cells in the first instance but also extend the analyses to other relevant CD4-positive subtypes where relevant.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003523","title":"MutWP5__CRUK_Mutographs_of_Cancer__BRCA_Carriers___WG__Novaseq_","description":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-11T15:53:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003524","title":"MutWP5__CRUK_Mutographs_of_Cancer__Breast__Reduction_Mammoplasty___WG__Novaseq_","description":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-11T15:56:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003525","title":"MutWP5__CRUK_Mutographs_of_Cancer__Cancer_Mastectomy__WG__Novaseq_","description":"Sequencing of LCM-derived microbiopsies from 40 women who underwent mastecomies due to breast cancer. LCM and sequencing will be conducted on both normal, unaffected breast, and, where possible, tumour tissue. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue, and compare findings between the normal and associated cancer tissues. Whole-genome sequencing will be conducted on samples identified as promising from the initial targeted data. Results from this poriton of the study will be compared to women who had cosmetic breast reduction surgeries and those who are BRCA carriers.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-11T15:59:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003526","title":"MutWP5__CRUK_Mutographs_of_Cancer__BRCA_Carriers___Exome__Novaseq_","description":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-11T16:02:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003527","title":"MutWP5__CRUK_Mutographs_of_Cancer__Breast__Reduction_Mammoplasty___Exome__Novaseq_","description":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-11T16:06:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003528","title":"MutWP5__CRUK_Mutographs_of_Cancer__Cancer_Mastectomy__Exome__Novaseq_","description":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-11T16:08:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003529","title":"Recapitulation of genetic predisposition to medulloblastoma in human neuroepithelial stem cells","description":"Human neural stem cell cultures provide progenitor cells that are potential cells of origin for brain cancers. However, the extent to which genetic predisposition to tumor formation can be faithfully captured in stem cell lines is uncertain. Here we evaluated neuroepithelial stem (NES) cells, representative of cerebellar progenitors. We transduced NES cells with MYCN, observing medulloblastoma upon orthotopic implantation in mice. Significantly, transcriptomes and patterns of DNA methylation from xenograft tumors were globally more representative of human medulloblastoma compared to a MYCN-driven genetically engineered mouse model. Orthotopic transplantation of NES cells generated from Gorlin syndrome, patients predisposed to medulloblastoma due to germline mutated PTCH1, also generated medulloblastoma. We engineered candidate cooperating mutations in Gorlin NES cells, with mutation of DDX3X or loss of GSE1 both accelerating tumorigenesis. These findings demonstrate that human NES cells provide a potent experimental resource for dissecting genetic causation in medulloblastoma.","abstract":"Human neural stem cell cultures provide progenitor cells that are potential cells of origin for brain cancers. However, the extent to which genetic predisposition to tumor formation can be faithfully captured in stem cell lines is uncertain. Here we evaluated neuroepithelial stem (NES) cells, representative of cerebellar progenitors. We transduced NES cells with MYCN, observing medulloblastoma upon orthotopic implantation in mice. Significantly, transcriptomes and patterns of DNA methylation from xenograft tumors were globally more representative of human medulloblastoma compared to a MYCN-driven genetically engineered mouse model. Orthotopic transplantation of NES cells generated from Gorlin syndrome, patients predisposed to medulloblastoma due to germline mutated PTCH1, also generated medulloblastoma. We engineered candidate cooperating mutations in Gorlin NES cells, with mutation of DDX3X or loss of GSE1 both accelerating tumorigenesis. These findings demonstrate that human NES cells provide a potent experimental resource for dissecting genetic causation in medulloblastoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003530","title":"Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors","description":"Cell-free tumour-derived DNA (ctDNA) allows non-invasive monitoring of various cancers but its utility in renal cell cancer (RCC) has not been well established. A combination of untargeted and targeted sequencing methods, applied to two independent cohorts of patients (n=90) with various renal tumour subtypes, were used to determine ctDNA content in plasma and urine. Our data revealed lower plasma ctDNA levels in RCC relative to other cancers, with untargeted detection of ~33% for both cohorts. A highly sensitive personalised approach, applied to plasma and urine from select patients (n=22), improved detection to ~50%, including in patients with early stage and even benign lesions. A machine-learning based model, applied to untargeted data, predicted this detection, potentially offering a means of triaging patient samples for personalised analysis. We observed that plasma, and for the first time, urine ctDNA may better represent tumour heterogeneity than a single tissue biopsy. Longitudinal sampling of &gt;200 plasma samples revealed that ctDNA can track disease course. These data highlight low ctDNA levels in RCC but indicate potential clinical utility provided improvement in isolation and detection approaches.","abstract":"Cell-free tumour-derived DNA (ctDNA) allows non-invasive monitoring of various cancers but its utility in renal cell cancer (RCC) has not been well established. A combination of untargeted and targeted sequencing methods, applied to two independent cohorts of patients (n=90) with various renal tumour subtypes, were used to determine ctDNA content in plasma and urine. Our data revealed lower plasma ctDNA levels in RCC relative to other cancers, with untargeted detection of ~33% for both cohorts. A highly sensitive personalised approach, applied to plasma and urine from select patients (n=22), improved detection to ~50%, including in patients with early stage and even benign lesions. A machine-learning based model, applied to untargeted data, predicted this detection, potentially offering a means of triaging patient samples for personalised analysis. We observed that plasma, and for the first time, urine ctDNA may better represent tumour heterogeneity than a single tissue biopsy. Longitudinal sampling of &gt;200 plasma samples revealed that ctDNA can track disease course. These data highlight low ctDNA levels in RCC but indicate potential clinical utility provided improvement in isolation and detection approaches.","study_type":"Other","pubmed_ids":[32111235],"external_links":null,"is_released":true,"released_date":"2019-03-12T15:10:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003531","title":"Melanoma_post_mortem_analysis","description":"This is a targeted pulldown validation in support of the existing whole-genome sequencing study of melanoma metastases (Canapps ID:1888). We are studying the genomic evolution of cutaneous melanoma metastases. In this pulldown analysis we are specifically sequencing the subclonal variants that we believe account for the variability between the metastases.","abstract":"Despite multiple large-scale sequencing studies offering substantial insight into the genomic landscape of cutaneous melanoma1, the molecular events surrounding disease progression and the resulting molecular heterogeneity between metastases have not been fully elucidated. Previous analyses across multiple metastases have revealed the coexistence of distinct tumour-immune microenvironments within the same individual. In order to gain an insight into the molecular structure of melanoma metastases, we have been applying whole genome and transcriptome sequencing across metastases collected during research post mortems. Herein we show the findings for the first such patient. Whole genome sequencing revealed that the metastases were dominated by a large cluster of fully clonal, mainly C&gt;T transitions, that were shared across all the tumours. However, removing the clonal variants revealed the true extend of underlying subclonal diversification, with evidence of waves of phylogenetic spread across multiple organs","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-13T13:12:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003532","title":"Sequencing of Infant high grade gliomas","description":"Infant high grade gliomas appear distinct from their counterparts in older children, indicating that grading may not accurately reflect the biology of these tumours. We have collected 228 cases under 4 years of age, and carried out histological review, methylation profiling (217), custom panel (15) and genome (20)/exome (12) sequencing. After excluding cases representing other established entities or subgroups, we identified 120 cases to be part of an intrinsic spectrum of disease in the infant population. These included those with targetable MAP-kinase alterations, and a large proportion of remaining cases to harbour gene fusions targeting ALK, NTRK1/2/3, ROS1 and MET as their driving alterations, with evidence of efficacy of targeted agents in the clinic. Infant gliomas require a change in diagnostic practise and management.","abstract":"Infant high grade gliomas appear distinct from their counterparts in older children, indicating that grading may not accurately reflect the biology of these tumours. We have collected 228 cases under 4 years of age, and carried out histological review, methylation profiling (217), custom panel (15) and genome (20)/exome (12) sequencing. After excluding cases representing other established entities or subgroups, we identified 120 cases to be part of an intrinsic spectrum of disease in the infant population. These included those with targetable MAP-kinase alterations, and a large proportion of remaining cases to harbour gene fusions targeting ALK, NTRK1/2/3, ROS1 and MET as their driving alterations, with evidence of efficacy of targeted agents in the clinic. Infant gliomas require a change in diagnostic practise and management.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-13T16:08:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003533","title":"WGS_Somatic_mutation_in_Primary_Sjogren_s_Syndrome","description":"The overall objective is to test the hypothesis that PSS is caused by somatic mutation of immune regulatory or checkpoint genes in lymphoid cells","abstract":"Autoimmune diseases affect 5% of the population and cause a wide range of painful disabilities that affect quality of life and may lead to life-threatening complications and early death.  In all these conditions, the immune system becomes hyperactive and damages tissues of the body including the joints, skin, mucous membranes, glands and vital organs.  In health, immune responses are closely regulated so that auto-immunity dose not occur.  Although research has identified many new ways to suppress auto-immunity, the reason why the immune system escapes from control in the first place, is completely unknown.\n\nThrough this research we are testing a new hypothesis that could explain why immune responses no longer respond to regulation in autoimmune disease.  Throughout life, tissues of the body accumulate genetic mutations due to random errors in copying the DNA when cells divide.  These mutations are known as 'somatic' mutations to indicate that they occur within an individual's lifetime and are not inherited from one generation to the next.  Somatic mutations are the cause of cancer and may play an important role in many chronic and age-related diseases.  Our research aims to test whether somatic mutations also cause autoimmunity.  The idea is that genes that control immune responses may become defective so that immune cells escape from normal regulatory signals.  There is evidence to support this idea from rare patients with inherited mutations that develop autoimmunity at a young age.  We also know that patients with autoimmunity, especially those with primary Sjogren's syndrome are at risk of developing lymphoma, a cancer of the immune system that involves exactly the same cells that cause autoimmunity.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003534","title":"The landscape of LAM disease","description":"Tumor biopsies from LAM disease were retrospectively analyzed by multiple techniques to characterize the  alterations  in patients ,to elucidate the landscape of genetic/genomic alterations.","abstract":"Tumor biopsies from LAM disease were retrospectively analyzed by multiple techniques to characterize the  alterations  in patients ,to elucidate the landscape of genetic/genomic alterations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-14T01:27:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003535","title":"Immune induction strategies to enhance the sensitivity to PD-1 blockade in metastatic triple negative breast cancer: the TONIC-trial","description":"The response rate in metastatic triple negative breast cancer (TNBC) to PD-1 blockade is low, highlighting an urgent clinical need for strategies that render the TNBC tumor microenvironment (TME) more sensitive to PD-1 blockade. Immunomodulatory mechanisms have been proposed for both chemotherapy and irradiation, but it has not been established whether these therapies may improve efficacy of PD-1 blockade by favorably changing the TME. In the first stage of this adaptive, non-comparative phase II trial (TONIC-trial; NCT02499367), 67 patients with metastatic TNBC were randomized to nivolumab without induction or to one of four induction treatments, consisting of irradiation of one metastatic lesion (3x8 Gy) or a two- week low-dose regimen of cyclophosphamide, cisplatin or doxorubicin, all followed by nivolumab. In the overall cohort of 66 evaluable patients, the objective response rate (ORR; iRECIST16) was 20% (95% CI: 11%-31%), with two complete responses and 11 partial responses. The majority of clinical responses were observed on nivolumab in the cisplatin (ORR 23%; 3/13) and doxorubicin (ORR 35%; 6/17) cohorts. After doxorubicin and cisplatin induction, we detected an upregulation of immune-related genes, involved in PD-1/PD-L1, and T-cell cytotoxicity pathways. This was further supported by enrichment among upregulated genes related to inflammation, JAK-STAT and TNFα-signaling after doxorubicin. In addition, we observed a trend towards increased T-cell infiltration, measured using T-cell receptor (TCR) sequencing, after doxorubicin. Together, the clinical and translational data of this study testing different immune induction strategies prior to nivolumab suggest that short-term doxorubicin and cisplatin may induce a more favorable TME and increase the likelihood of response to PD-1 blockade in TNBC. These data warrant further confirmation in TNBC and exploration of induction treatments prior to PD-1 blockade in other cancer types.","abstract":"The response rate in metastatic triple negative breast cancer (TNBC) to PD-1 blockade is low, highlighting an urgent clinical need for strategies that render the TNBC tumor microenvironment (TME) more sensitive to PD-1 blockade. Immunomodulatory mechanisms have been proposed for both chemotherapy and irradiation, but it has not been established whether these therapies may improve efficacy of PD-1 blockade by favorably changing the TME. In the first stage of this adaptive, non-comparative phase II trial (TONIC-trial; NCT02499367), 67 patients with metastatic TNBC were randomized to nivolumab without induction or to one of four induction treatments, consisting of irradiation of one metastatic lesion (3x8 Gy) or a two- week low-dose regimen of cyclophosphamide, cisplatin or doxorubicin, all followed by nivolumab. In the overall cohort of 66 evaluable patients, the objective response rate (ORR; iRECIST16) was 20% (95% CI: 11%-31%), with two complete responses and 11 partial responses. The majority of clinical responses were observed on nivolumab in the cisplatin (ORR 23%; 3/13) and doxorubicin (ORR 35%; 6/17) cohorts. After doxorubicin and cisplatin induction, we detected an upregulation of immune-related genes, involved in PD-1/PD-L1, and T-cell cytotoxicity pathways. This was further supported by enrichment among upregulated genes related to inflammation, JAK-STAT and TNFα-signaling after doxorubicin. In addition, we observed a trend towards increased T-cell infiltration, measured using T-cell receptor (TCR) sequencing, after doxorubicin. Together, the clinical and translational data of this study testing different immune induction strategies prior to nivolumab suggest that short-term doxorubicin and cisplatin may induce a more favorable TME and increase the likelihood of response to PD-1 blockade in TNBC. These data warrant further confirmation in TNBC and exploration of induction treatments prior to PD-1 blockade in other cancer types.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-14T12:42:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003536","title":"Tumor-derived cell lines as pharmacogenomic models to predict therapeutic vulnerabilities in hepatocellular carcinoma","description":"Hepatocellular carcinoma (HCC) is a heterogeneous aggressive malignancy with low efficacy of current therapies at advanced stages. We integrated molecular and pharmacological profiling of a large panel of liver cancer cell lines (LCCL) to assess their clinical relevance as HCC preclinical models and identify new effective therapies and biomarkers of response. We performed multi-omic analysis including whole-exome, RNA and miRNA sequencing and quantification of 126 proteins in a series 34 LCCL coupled with a screening of 29 anti-cancer agents. Molecular profiles of LCCL and primary HCC were compared and we searched for molecular features associated with drug response. Our panel of LCCL faithfully recapitulated the most aggressive molecular \"proliferation class\" of HCC. Genomic alterations of the RAS-MAPK pathway correlated with trametinib sensitivity that was more potent than FGFR4 inhibitors in tumor cells depending on the FGF19/FGFR4 pathway. Moreover, we showed that FGF19 amplification was only functional in tumor cells that retained a hepatocyte differentiation program with expression of FGFR4, KLB and NR1H4 highlighting the complex interplay between the genomic and transcriptomic context in drug response. We also identified drugs/combination that could target efficiently the transcriptomic \"progenitor subclass of HCC\", as well as specific genetic contexts such as inactivating mutations in TSC1/TSC2 and TP53 associated with higher sensitivity to the mTOR inhibitor rapamycin and the AURKA inhibitor alisertib, respectively. LCCL represent relevant preclinical models for drug-biomarker discovery in HCC and enabled to identify molecular contexts linked with particular therapeutic vulnerabilities that may be useful to stratify patients in future clinical trials","abstract":"Hepatocellular carcinoma (HCC) is a heterogeneous aggressive malignancy with low efficacy of current therapies at advanced stages. We integrated molecular and pharmacological profiling of a large panel of liver cancer cell lines (LCCL) to assess their clinical relevance as HCC preclinical models and identify new effective therapies and biomarkers of response. We performed multi-omic analysis including whole-exome, RNA and miRNA sequencing and quantification of 126 proteins in a series 34 LCCL coupled with a screening of 29 anti-cancer agents. Molecular profiles of LCCL and primary HCC were compared and we searched for molecular features associated with drug response. Our panel of LCCL faithfully recapitulated the most aggressive molecular \"proliferation class\" of HCC. Genomic alterations of the RAS-MAPK pathway correlated with trametinib sensitivity that was more potent than FGFR4 inhibitors in tumor cells depending on the FGF19/FGFR4 pathway. Moreover, we showed that FGF19 amplification was only functional in tumor cells that retained a hepatocyte differentiation program with expression of FGFR4, KLB and NR1H4 highlighting the complex interplay between the genomic and transcriptomic context in drug response. We also identified drugs/combination that could target efficiently the transcriptomic \"progenitor subclass of HCC\", as well as specific genetic contexts such as inactivating mutations in TSC1/TSC2 and TP53 associated with higher sensitivity to the mTOR inhibitor rapamycin and the AURKA inhibitor alisertib, respectively. LCCL represent relevant preclinical models for drug-biomarker discovery in HCC and enabled to identify molecular contexts linked with particular therapeutic vulnerabilities that may be useful to stratify patients in future clinical trials","study_type":"Other","pubmed_ids":[31063779],"external_links":null,"is_released":true,"released_date":"2019-03-15T09:33:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003537","title":"Bioresource_and_clonal_disorders_samples_for_botseq","description":"Validation of botseq on granulocytes from donors of different ages.","abstract":"Botseq will be performed on DNA derived from granulocytes from donors of different ages.  In addition bulk whole genome sequencing will be performed to act as a matched normal genome.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003538","title":"Whole_Genome_Sequencing_of_Human_Organoid_Lines","description":"The study will use WGS to aid in benchmarking different culture conditions  in a set of genetically annotated human organoid lines. The data will be used to assess whether there is any clonal differences introduced when culturing these lines in different conditions.","abstract":"The study will use WGS to aid in benchmarking different culture conditions  in a set of genetically annotated human organoid lines. The data will be used to assess whether there is any clonal differences introduced when culturing these lines in different conditions.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-15T12:38:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003539","title":"Clonal evolution in myeloma: the impact of maintenance lenalidomide and depth of response on the genetics and sub-clonal structure of relapsed disease in uniformly treated newly diagnosed patients","description":"The emergence of treatment resistant sub-clones is a key feature of relapse in multiple myeloma. Therapeutic attempts to extend remission and prevent relapse include the maximisation of response and use of maintenance therapy. We used whole exome sequencing to study the genetics of paired presentation and relapse samples from 56 newly diagnosed patients, following induction therapy, randomised to receive either lenalidomide maintenance or observation as part of the Myeloma XI trial. Patients included were considered high risk, relapsing within 30 months of maintenance randomisation. Patients achieving a complete response had predominantly branching evolutionary patterns leading to relapse, characterised by a greater mutational burden, an altered mutational profile, bi-allelic inactivation of tumour suppressor genes, and acquired structural aberrations. Conversely, in patients achieving a partial response the evolutionary features were predominantly stable with a similar mutational and structural profile. There were no significant differences between patients relapsing after maintenance lenalidomide vs observation. This study shows that the depth of response is a key determinant of the evolutionary patterns seen at relapse.","abstract":"The emergence of treatment resistant sub-clones is a key feature of relapse in multiple myeloma. Therapeutic attempts to extend remission and prevent relapse include the maximisation of response and use of maintenance therapy. We used whole exome sequencing to study the genetics of paired presentation and relapse samples from 56 newly diagnosed patients, following induction therapy, randomised to receive either lenalidomide maintenance or observation as part of the Myeloma XI trial. Patients included were considered high risk, relapsing within 30 months of maintenance randomisation. Patients achieving a complete response had predominantly branching evolutionary patterns leading to relapse, characterised by a greater mutational burden, an altered mutational profile, bi-allelic inactivation of tumour suppressor genes, and acquired structural aberrations. Conversely, in patients achieving a partial response the evolutionary features were predominantly stable with a similar mutational and structural profile. There were no significant differences between patients relapsing after maintenance lenalidomide vs observation. This study shows that the depth of response is a key determinant of the evolutionary patterns seen at relapse.","study_type":"Other","pubmed_ids":[30733268],"external_links":null,"is_released":true,"released_date":"2019-03-15T15:03:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003540","title":"Genomic and transcriptomic landscape of aggressive thyroid cancer","description":"Molecular characteristics of anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) have not been fully elucidated. In this study, we applied various types of massively-parallel sequencing technology to 113 advanced TCs, including 27 ATCs and 86 advanced DTCs, to reveal their genomic and transcriptomic characteristics.","abstract":"Molecular characteristics of anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) have not been fully elucidated. In this study, we applied various types of massively-parallel sequencing technology to 113 advanced TCs, including 27 ATCs and 86 advanced DTCs, to reveal their genomic and transcriptomic characteristics.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-16T04:59:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003541","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___UGI___WGS","description":"The aim of this project is to investiagte somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the studyof normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to idnetifiy and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","abstract":"The aim of this project is to investiagte somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the studyof normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to idnetifiy and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-18T11:42:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003542","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__clear_cell_renal_cell_carcinoma___2","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-18T14:58:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003543","title":"DIME","description":null,"abstract":"Safety, dose-response and efficacy of treatment with Eubacterium hallii L2-7 on glucose metabolism\nin human subjects with metabolic syndrome","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003544","title":"RNA sequencing of NK cells in human lung","description":"Human lung tissue-resident NK cells (trNK cells) are likely to play important roles in viral infections, inflammation and cancer. However, knowledge about lung trNK cells is lacking but is fundamental for exploiting these cells in therapeutic approaches. Here we analysed the transcriptome of CD69+CD49a+CD103+CD16-CD56bright, CD69+CD49a+CD103-CD16-CD56bright, CD69+CD49a-CD103-CD16-CD56bright, CD69-CD49a-CD103-CD16-CD56bright, and CD56dimCD16+NKG2A+CD57- NK cells isolated from human lung.","abstract":"Human lung tissue-resident NK cells (trNK cells) are likely to play important roles in viral infections, inflammation and cancer. However, knowledge about lung trNK cells is lacking but is fundamental for exploiting these cells in therapeutic approaches. Here we analysed the transcriptome of CD69+CD49a+CD103+CD16-CD56bright, CD69+CD49a+CD103-CD16-CD56bright, CD69+CD49a-CD103-CD16-CD56bright, CD69-CD49a-CD103-CD16-CD56bright, and CD56dimCD16+NKG2A+CD57- NK cells isolated from human lung.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-18T17:21:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003545","title":"Genomics analysis of mucinous tumours of the ovary and related neoplasms","description":"To perform genetic and gene expression analyses on mucinous ovarian tumours to determine a progression model, cell of origin and novel therapeutic targets.","abstract":"To perform genetic and gene expression analyses on mucinous ovarian tumours to determine a progression model, cell of origin and novel therapeutic targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-19T06:49:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003546","title":"Evolution of GBM through therapy","description":"Primary glioblastoma (GBM) tumours recur following treatment. This is likely due to intratumour heterogeneity (ITH), which reduces the effectiveness of cancer therapies by enabling therapy-driven tumour evolution: Darwinian selection of genotypically and/or phenotypically distinct cells (subclones) that resist treatment to seed regrowth of an even less treatable recurrence. To investigate this we sequenced a pilot cohort of nine paired primary and locally recurrent GBM tumours, alongside matched blood samples, in order to begin characterising therapy resistant cells and thereby infer the mechanisms by which they evaded treatment. These data were included in the first data release from the Glioma Longitudinal AnalySiS (GLASS) consortium.","abstract":"Primary glioblastoma (GBM) tumours recur following treatment. This is likely due to intratumour heterogeneity (ITH), which reduces the effectiveness of cancer therapies by enabling therapy-driven tumour evolution: Darwinian selection of genotypically and/or phenotypically distinct cells (subclones) that resist treatment to seed regrowth of an even less treatable recurrence. To investigate this we sequenced a pilot cohort of nine paired primary and locally recurrent GBM tumours, alongside matched blood samples, in order to begin characterising therapy resistant cells and thereby infer the mechanisms by which they evaded treatment. These data were included in the first data release from the Glioma Longitudinal AnalySiS (GLASS) consortium.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-20T13:54:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003547","title":"Germline variants collaborate with somatic mutations and initiate and/or drive disease in primary myelodysplastic syndrome (MDS) and therapy-related myeloid neoplasms (t-MN)","description":"Therapy-related myeloid neoplasms (T-MN) are poorly characterized secondary hematological malignancies following chemotherapy/radiotherapy exposure. We compared the clinical and mutational characteristics of T-MN (n=129) and primary myelodysplastic syndrome (P-MDS, n=108) patients. Although the somatic mutation frequency was similar between T-MN and P-MDS patients (93% in both groups), the pattern was distinct. TP53 mutations were more frequent in T-MN (29.5% versus 7%), while spliceosomal complex mutations were more common in P-MDS (56.5% versus 25.6%).In contrast to P-MDS, the ring sideroblasts (RS) phenotype was not associated with better survival in T-MN, most probably due to genetic association with TP53 mutations. SF3B1 was mutated in 96% of P-MDS with ≥15% RS, but in only 32% T-MN. TP53 mutations were detected in 92% T-MN with ≥15% RS and SF3B1 wild-type cases. Interestingly, T-MN and P-MDS patients with “Very low” or “Low” Revised International Prognostic Scoring System (IPSS-R) showed similar biological and clinical characteristics. In a Cox-regression analysis, TP53 mutation was a poor prognostic factor in T-MN, independent of IPSS-R cytogenetic, disease-modifying therapy and NRAS mutation.Our data have direct implications for T-MN management and provide evidence that, in addition to conventional disease parameters, mutational analysis should be incorporated in T-MN risk stratification.","abstract":"Therapy-related myeloid neoplasms (T-MN) are poorly characterized secondary hematological malignancies following chemotherapy/radiotherapy exposure. We compared the clinical and mutational characteristics of T-MN (n=129) and primary myelodysplastic syndrome (P-MDS, n=108) patients. Although the somatic mutation frequency was similar between T-MN and P-MDS patients (93% in both groups), the pattern was distinct. TP53 mutations were more frequent in T-MN (29.5% versus 7%), while spliceosomal complex mutations were more common in P-MDS (56.5% versus 25.6%).In contrast to P-MDS, the ring sideroblasts (RS) phenotype was not associated with better survival in T-MN, most probably due to genetic association with TP53 mutations. SF3B1 was mutated in 96% of P-MDS with ≥15% RS, but in only 32% T-MN. TP53 mutations were detected in 92% T-MN with ≥15% RS and SF3B1 wild-type cases. Interestingly, T-MN and P-MDS patients with “Very low” or “Low” Revised International Prognostic Scoring System (IPSS-R) showed similar biological and clinical characteristics. In a Cox-regression analysis, TP53 mutation was a poor prognostic factor in T-MN, independent of IPSS-R cytogenetic, disease-modifying therapy and NRAS mutation.Our data have direct implications for T-MN management and provide evidence that, in addition to conventional disease parameters, mutational analysis should be incorporated in T-MN risk stratification.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-20T22:40:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003548","title":"Rare coding variants in lupus risk genes","description":"Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. It is thought that many common variant gene loci of weak effect act additively to predispose to common autoimmune diseases, while the contribution of rare variants remains unclear. Here we describe that rare coding variants in lupus-risk genes are present in most SLE patients and healthy controls. We demonstrate the functional consequences of rare and low frequency missense variants in the interacting proteins BLK and BANK1, which are present alone, or in combination, in a substantial proportion of lupus patients. The rare variants found in patients, but not those found exclusively in controls, impair suppression of IRF5 and type-I IFN in human B cell lines and increase pathogenic lymphocytes in lupus-prone mice. Thus, rare gene variants are common in SLE and likely contribute to genetic risk.","abstract":"Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. It is thought that many common variant gene loci of weak effect act additively to predispose to common autoimmune diseases, while the contribution of rare variants remains unclear. Here we describe that rare coding variants in lupus-risk genes are present in most SLE patients and healthy controls. We demonstrate the functional consequences of rare and low frequency missense variants in the interacting proteins BLK and BANK1, which are present alone, or in combination, in a substantial proportion of lupus patients. The rare variants found in patients, but not those found exclusively in controls, impair suppression of IRF5 and type-I IFN in human B cell lines and increase pathogenic lymphocytes in lupus-prone mice. Thus, rare gene variants are common in SLE and likely contribute to genetic risk.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-21T04:51:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003549","title":"Placental_mosaicism","description":"The aim of this study is to survey somatic mutations in human placentas.","abstract":"The aim of this study is to survey somatic mutations in human placentas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-21T10:19:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003550","title":"HSC_population_dynamics___KX003_samples","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-21T16:39:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003551","title":"DLBCL WES data","description":null,"abstract":"Programmed death – ligand 1 (PD-L1) expression on malignant cells is a dominant immune escape mechanism across a variety of human cancers. A unique genetic mechanism underlying PD-L1 up-regulation has been uncovered in classical Hodgkin lymphoma (cHL), in which copy gains of the chromosomal region (9p24.1) containing the PD-1 ligands (PD-L1 and PD-L2) are recurrently observed. While chromosome 9p24.1 copy number alterations are ubiquitous in cHL, they also occur in diffuse large B cell lymphoma (DLBCL), albeit with a lower incidence. Here, FISH was utilized to identify DLBCLs harboring PD-L1 gene alterations, thereby enabling a characterization of the immunogenomiclandscape of these lymphomas. Among 105 DLBCL cases analyzed, PD-L1 alterations were identified in 27%. PD-L1 alterations were highly enriched among non-germinal center DLBCLs, and were correlated with robust PD-L1 protein expression. These lymphomas were heavily infiltrated by clonally-restricted T cells, and frequently down-regulated human leukocyte antigen expression. RNA-sequencing of PD-L1 altered DLBCLs revealed up-regulation of genes involved in negative T cell regulation and NF-κB pathway activation, while whole exome sequencing identified frequent mutations in genes involved in antigen presentation and T cell co-stimulation. Patients with PD-L1 gene-altered DLBCL had inferior progression-free survival following front-line chemo-immunotherapy. Importantly, in the relapsed/refractory setting, the presence of PD-L1 alterations was associated with response to anti-PD-1 therapy. Collectively, our results indicate that PD-L1 alterations identify a unique biological subset of DLBCL in which an endogenous anti-lymphoma immune response has been activated, and which is associated with responsiveness to PD-1 blockade therapy.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003552","title":"DLBCL RNAseq data","description":null,"abstract":"Programmed death – ligand 1 (PD-L1) expression on malignant cells is a dominant immune escape mechanism across a variety of human cancers. A unique genetic mechanism underlying PD-L1 up-regulation has been uncovered in classical Hodgkin lymphoma (cHL), in which copy gains of the chromosomal region (9p24.1) containing the PD-1 ligands (PD-L1 and PD-L2) are recurrently observed. While chromosome 9p24.1 copy number alterations are ubiquitous in cHL, they also occur in diffuse large B cell lymphoma (DLBCL), albeit with a lower incidence. Here, FISH was utilized to identify DLBCLs harboring PD-L1 gene alterations, thereby enabling a characterization of the immunogenomiclandscape of these lymphomas. Among 105 DLBCL cases analyzed, PD-L1 alterations were identified in 27%. PD-L1 alterations were highly enriched among non-germinal center DLBCLs, and were correlated with robust PD-L1 protein expression. These lymphomas were heavily infiltrated by clonally-restricted T cells, and frequently down-regulated human leukocyte antigen expression. RNA-sequencing of PD-L1 altered DLBCLs revealed up-regulation of genes involved in negative T cell regulation and NF-κB pathway activation, while whole exome sequencing identified frequent mutations in genes involved in antigen presentation and T cell co-stimulation. Patients with PD-L1 gene-altered DLBCL had inferior progression-free survival following front-line chemo-immunotherapy. Importantly, in the relapsed/refractory setting, the presence of PD-L1 alterations was associated with response to anti-PD-1 therapy. Collectively, our results indicate that PD-L1 alterations identify a unique biological subset of DLBCL in which an endogenous anti-lymphoma immune response has been activated, and which is associated with responsiveness to PD-1 blockade therapy.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003553","title":"To_profile_the_landscape_of_sebaceous_tumours_WES","description":"Sebaceous tumours are a rare cutaneous cancer with potential for aggressive behaviour. However, limited information is available on these cancers with few published cases. Here we wish to exome sequence these cancers to define the first genomic landscape for this malignancy. We will extract DNA from formalin-fixed, paraffin-embedded (FFPE) cores. Cores may be obtained from lesional and non-lesional tissues of primaries as well as matching metastases. The extracted DNA will be used for exome sequencing.","abstract":"Sebaceous tumours are a rare cutaneous cancer with potential for aggressive behaviour. However, limited information is available on these cancers with few published cases. Here we wish to exome sequence these cancers to define the first genomic landscape for this malignancy. We will extract DNA from formalin-fixed, paraffin-embedded (FFPE) cores. Cores may be obtained from lesional and non-lesional tissues of primaries as well as matching metastases. The extracted DNA will be used for exome sequencing.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-22T12:57:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003554","title":"Arriba: accurate and efficient detection of gene fusions from RNA-Seq (H021)","description":"The identification of gene fusions from RNA sequencing data is a routine task in cancer research and precision oncology. However, despite the availability of many computational tools, fusion detection remains challenging. Existing methods suffer from poor prediction accuracy and are computationally demanding. We developed Arriba, a novel fusion detection algorithm with high sensitivity and short runtime. When applied to a large collection of published pancreatic cancer samples (n=803), Arriba identified a variety of driver fusions, many of which affected druggable proteins, including ALK, BRAF, FGFR2, NRG1, NTRK1, NTRK3, RET, and ROS1. The fusions were significantly associated with KRAS wild-type tumors and involved proteins stimulating the MAPK signaling pathway, suggesting that they substitute for activating mutations in KRAS. In addition, we confirmed the transforming potential of two novel fusions, RRBP1-RAF1 and RASGRP1-ATP1A1, in cellular assays. These results demonstrate Arriba’s utility in both basic cancer research and clinical translation.","abstract":"The identification of gene fusions from RNA sequencing data is a routine task in cancer research and precision oncology. However, despite the availability of many computational tools, fusion detection remains challenging. Existing methods suffer from poor prediction accuracy and are computationally demanding. We developed Arriba, a novel fusion detection algorithm with high sensitivity and short runtime. When applied to a large collection of published pancreatic cancer samples (n=803), Arriba identified a variety of driver fusions, many of which affected druggable proteins, including ALK, BRAF, FGFR2, NRG1, NTRK1, NTRK3, RET, and ROS1. The fusions were significantly associated with KRAS wild-type tumors and involved proteins stimulating the MAPK signaling pathway, suggesting that they substitute for activating mutations in KRAS. In addition, we confirmed the transforming potential of two novel fusions, RRBP1-RAF1 and RASGRP1-ATP1A1, in cellular assays. These results demonstrate Arriba’s utility in both basic cancer research and clinical translation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-22T15:43:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003555","title":"Revealing active mutational processes in tumours using DigiPico/MutLX at unprecedented accuracy","description":"Active mutational processes in a tumor result in genetic micro-heterogeneity that can determine the tumor’s evolutionary trajectory. Identification of these processes by studying micro-heterogeneity can unveil novel aspects of tumor evolution with potential therapeutic implications. Such studies, however, are inherently problematic because of the discovery of excessive false positive mutations. Here we report the optimization and validation of a robust whole genome sequencing and analysis pipeline (DigiPico/MutLX) that virtually eliminates false positive results. Using our method, we identified, for the first time, a sub-clonal local hyper-mutation (kataegis) event in a recurrent ovarian carcinoma, which was unidentifiable from the bulk WGS data of the same tumor. Overall, we propose DigiPico/MutLX method as a powerful framework for the reliable study of genetic micro-heterogeneity in tumor and normal tissues.","abstract":"Active mutational processes in a tumor result in genetic micro-heterogeneity that can determine the tumor’s evolutionary trajectory. Identification of these processes by studying micro-heterogeneity can unveil novel aspects of tumor evolution with potential therapeutic implications. Such studies, however, are inherently problematic because of the discovery of excessive false positive mutations. Here we report the optimization and validation of a robust whole genome sequencing and analysis pipeline (DigiPico/MutLX) that virtually eliminates false positive results. Using our method, we identified, for the first time, a sub-clonal local hyper-mutation (kataegis) event in a recurrent ovarian carcinoma, which was unidentifiable from the bulk WGS data of the same tumor. Overall, we propose DigiPico/MutLX method as a powerful framework for the reliable study of genetic micro-heterogeneity in tumor and normal tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-24T08:33:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003556","title":"Pharmacogenomic analysis of patient-derived tumor cells in gynecologic cancers","description":"Gynecologic malignancy is one of the leading causes of mortality in female adults worldwide. Comprehensive genomic analysis has revealed a list of molecular aberrations that are essential to tumorigenesis, progression, and metastasis of gynecologic tumors. However, targeting such alterations has frequently led to treatment failures due to underlying genomic complexity and activation of various tumor cell survival pathway molecules. A compilation of molecular characterization of tumors with pharmacological drug response is the next step towards clinical application of patient-tailored treatment regimens. Toward this goal, we have established a library of 139 gynecologic tumors including cervical, endometrial, and epithelial ovarian cancers (EOCs) and uterine sarcomas that were genomically and/or pharmacologically annotated and explored dynamic pharmacogenomic associations against 37 molecularly targeted drugs. We discovered lineage-specific drug sensitivities based on subcategorization of gynecologic tumors and identified TP53 mutation as a molecular determinant that elicit therapeutic response to poly (ADP-Ribose) polymerase (PARP) inhibitor. We further identified transcriptome expression of inhibitor of DNA biding 2 (ID2) as a potential predictive biomarker for treatment response to olaparib. Together, our results demonstrate potential utility of rapid drug screening combined with genomic profiling for precision treatment of gynecologic cancers.","abstract":"Gynecologic malignancy is one of the leading causes of mortality in female adults worldwide. Comprehensive genomic analysis has revealed a list of molecular aberrations that are essential to tumorigenesis, progression, and metastasis of gynecologic tumors. However, targeting such alterations has frequently led to treatment failures due to underlying genomic complexity and activation of various tumor cell survival pathway molecules. A compilation of molecular characterization of tumors with pharmacological drug response is the next step towards clinical application of patient-tailored treatment regimens. Toward this goal, we have established a library of 139 gynecologic tumors including cervical, endometrial, and epithelial ovarian cancers (EOCs) and uterine sarcomas that were genomically and/or pharmacologically annotated and explored dynamic pharmacogenomic associations against 37 molecularly targeted drugs. We discovered lineage-specific drug sensitivities based on subcategorization of gynecologic tumors and identified TP53 mutation as a molecular determinant that elicit therapeutic response to poly (ADP-Ribose) polymerase (PARP) inhibitor. We further identified transcriptome expression of inhibitor of DNA biding 2 (ID2) as a potential predictive biomarker for treatment response to olaparib. Together, our results demonstrate potential utility of rapid drug screening combined with genomic profiling for precision treatment of gynecologic cancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-25T03:25:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003557","title":"HG_Mosaic_Mobile_Elements_in_DDD","description":"Mobile genetic Elements (MEs) are pieces of DNA which, through an RNA intermediate, can generate new copies of themselves elsewhere in the host genome. As part of the Deciphering Developmental Disorders study, we have discovered and genotyped ~10K trios (child, mom, and dad) for three types of mobile genetic elements, Alu, L1, and SVA. During the course of our analysis we identified 17 variants found in a single proband (i.e. singletons) and with low allelic depth (i.e. a low proportion of sequencing reads supporting the new ME copy) in only one parent. As part of the review process for our manuscript on MEs, we were asked to determine if some of these vairants may actually be mosaic in the parent, or not present in every cell of the particular individuals body. To determine the mosaic status of each of our 17 variants, we plan to use long-amplicon PCR coupled with Pacific Biosciences sequencing to attempt to phase our MEs with nearby heterozygous SNVs. If the haplotype carrying the nearby heterozygous SNV only supports the insertion event in less than 50 percent of reads, then our variants are likely mosaic. With this information, we can both better understand the transmission of mosaic MEs from parent to offspring, as well as potentially identify variants that had no impact in the parent but could lead to a disorder in the proband.","abstract":"Mobile genetic Elements (MEs) are pieces of DNA which, through an RNA intermediate, can generate new copies of themselves elsewhere in the host genome. As part of the Deciphering Developmental Disorders study, we have discovered and genotyped ~10K trios (child, mom, and dad) for three types of mobile genetic elements, Alu, L1, and SVA. During the course of our analysis we identified 17 variants found in a single proband (i.e. singletons) and with low allelic depth (i.e. a low proportion of sequencing reads supporting the new ME copy) in only one parent. As part of the review process for our manuscript on MEs, we were asked to determine if some of these vairants may actually be mosaic in the parent, or not present in every cell of the particular individuals body. To determine the mosaic status of each of our 17 variants, we plan to use long-amplicon PCR coupled with Pacific Biosciences sequencing to attempt to phase our MEs with nearby heterozygous SNVs. If the haplotype carrying the nearby heterozygous SNV only supports the insertion event in less than 50 percent of reads, then our variants are likely mosaic. With this information, we can both better understand the transmission of mosaic MEs from parent to offspring, as well as potentially identify variants that had no impact in the parent but could lead to a disorder in the proband.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003558","title":"Colorectal cancer organoids expressing BRAF (fusion) genes","description":"Fusion genes may be oncogenic drivers and potential targets for personalized therapies in a variety of cancer types. The BRAF gene is frequently involved in oncogenic fusions, with fusion frequencies of 0.2-3% throughout different cancers. BRAF can be fused to a wide variety of genes, however, BRAF fusions rarely occur in the exact same gene configuration, making assessment of the fusion relevance and decision for drug treatment challenging. Here, we devised a colorectal cancer organoid-based platform to functionally characterize diverse BRAF fusions, containing various partner genes (AGAP3, DLG1 and TRIM24). We compared these BRAF fusions with respect to cellular behaviour, downstream signaling activation and response to targeted therapies. We found that 5’ partner choice of BRAF affects cellular localization and intracellular signaling capacities of the fusion genes. The DLG1-BRAF fusion gene showed distinct localization to the plasma membrane and exhibited increased levels of MAPK pathway activation under unperturbed conditions. Furthermore, the different BRAF fusions showed varying sensitivities to the targeted inhibition of ERK and BRAF, with the DLG1-BRAF fusion being the most sensitive. Additionally, RNA-sequencing identified distinct subsets of genes affected by the DLG1-BRAF fusion gene. Importantly, all fusion genes conveyed resistance to the clinically relevant EGFR/HER2/HER4-inhibitor afatinib, suggesting that BRAF fusions should be screened alongside other MAPK pathway alterations to identify mCRC patients amenable to cetuximab treatment. In summary, we developed a platform to efficiently assess molecular and cellular effects of fusion genes, and revealed that differential drug responses and distinct gene expression profiles can be induced by different BRAF fusions .","abstract":"Fusion genes may be oncogenic drivers and potential targets for personalized therapies in a variety of cancer types. The BRAF gene is frequently involved in oncogenic fusions, with fusion frequencies of 0.2-3% throughout different cancers. BRAF can be fused to a wide variety of genes, however, BRAF fusions rarely occur in the exact same gene configuration, making assessment of the fusion relevance and decision for drug treatment challenging. Here, we devised a colorectal cancer organoid-based platform to functionally characterize diverse BRAF fusions, containing various partner genes (AGAP3, DLG1 and TRIM24). We compared these BRAF fusions with respect to cellular behaviour, downstream signaling activation and response to targeted therapies. We found that 5’ partner choice of BRAF affects cellular localization and intracellular signaling capacities of the fusion genes. The DLG1-BRAF fusion gene showed distinct localization to the plasma membrane and exhibited increased levels of MAPK pathway activation under unperturbed conditions. Furthermore, the different BRAF fusions showed varying sensitivities to the targeted inhibition of ERK and BRAF, with the DLG1-BRAF fusion being the most sensitive. Additionally, RNA-sequencing identified distinct subsets of genes affected by the DLG1-BRAF fusion gene. Importantly, all fusion genes conveyed resistance to the clinically relevant EGFR/HER2/HER4-inhibitor afatinib, suggesting that BRAF fusions should be screened alongside other MAPK pathway alterations to identify mCRC patients amenable to cetuximab treatment. In summary, we developed a platform to efficiently assess molecular and cellular effects of fusion genes, and revealed that differential drug responses and distinct gene expression profiles can be induced by different BRAF fusions .","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-26T10:32:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003559","title":"Characterization of retrotransposon insertions in colorectal cancers","description":null,"abstract":"Genomic instability pathways in colorectal cancer (CRC) have been extensively studied, but the role of retrotransposition in colorectal carcinogenesis remains poorly understood. Although retrotransposons are usually repressed, they become active in several human cancers, in particular those of the gastrointestinal tract. Here we characterize retrotransposon insertions in 202 colorectal tumor whole genomes and investigate their associations with molecular and clinical characteristics. We find highly variable retrotransposon activity among tumors and identify recurrent insertions in 15 known cancer genes. In approximately 1% of the cases we identify insertions in APC, likely to be tumor-initiating events. Insertions are positively associated with the CpG island methylator phenotype and the genomic fraction of allelic imbalance. Clinically, high number of insertions is independently associated with poor disease-specific survival.\n\nThis RNA-seq study was funded by SYSCOL (an EU FP7 Collaborative Project, 258236).","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003560","title":"Genetic modification of primary human B cells to model high-grade lymphoma","description":null,"abstract":"Sequencing studies of non-Hodgkin lymphoma genomes have identified hundreds of recurrently altered genes. However, it remains largely unknown whether and how these mutations may contribute to lymphomagenesis, either individually or in combination. Existing strategies to address this problem predominantly utilise cell lines, which are limited by their initial characteristics and subsequent adaptions to prolonged in vitro culture. Here, we describe a novel co-culture system that enables the ex vivo expansion and viral transduction of primary human germinal centre B cells. The incorporation of CRISPR/Cas9 technology enables high-throughput functional interrogation of gene mutations found recurrently in DLBCL. Using a backbone of BCL2 with either BCL6 or MYC we have identified co-operating oncogenes that promote growth and survival, or even full transformation into synthetically engineered models of DLBCL. The resulting tumours can be expanded and sequentially transplanted in vivo, providing a scalable platform to test putative cancer genes and for the creation of mutation-directed, bespoke lymphoma models.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-27T10:09:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003561","title":"Three-dimensional Chromatin Landscapes of Human Early Embryos at Single-cell Resolution.","description":"Rapid progresses in the chromosome conformation capture technique accelerate our understanding of three-dimentional architecture of chromatin in cell nucleus. To achieve the distant fine regulation, the genome organized into a series of compartments, topologically associating domains (TADs) and loops at different genomic scales, in which the spatial distance decreases between distinct regulatory regions. The dynamics of highly-ordered genome after fertilization have been extensively explored in model animal system, which revealed that the establishment of genomic compartmentalization gradually occurred after zygote gene activation meanwhile partially independent of transcription. However, it remains unclear how the chromatin architecture is built during human preimplantation embryos development. By single-cell Hi-C, we investigate the feature of chromatin conformation in this crucial process and compare the conservation extent between human and mouse.","abstract":"Rapid progresses in the chromosome conformation capture technique accelerate our understanding of three-dimentional architecture of chromatin in cell nucleus. To achieve the distant fine regulation, the genome organized into a series of compartments, topologically associating domains (TADs) and loops at different genomic scales, in which the spatial distance decreases between distinct regulatory regions. The dynamics of highly-ordered genome after fertilization have been extensively explored in model animal system, which revealed that the establishment of genomic compartmentalization gradually occurred after zygote gene activation meanwhile partially independent of transcription. However, it remains unclear how the chromatin architecture is built during human preimplantation embryos development. By single-cell Hi-C, we investigate the feature of chromatin conformation in this crucial process and compare the conservation extent between human and mouse.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003562","title":"Single-cell Genomic and Transcriptomic Landscapes of Primary and Metastatic Tumors in Colorectal Cancer","description":"Here we performed a single-cell RNA-Seq survey of 7,438 cells from 9 metastatic CRC patients, from whom matching adjacent normal tissues, primary tumors, and metastatic tumors were simultaneously sampled. Moreover, we also performed whole genome sequencing (WGS) on 81 sampled regions of these 9 patients and multi-region whole exome sequencing (WES) on 35 sample regions from 3 of these patients (patient #7-#9). We analyzed the dynamics of cell-type compositions, genomic copy number variants (CNVs), gene expression signatures, crosstalk between cancer cells and microenvironment cells and somatic mutations during CRC tumorigenesis and metastasis.","abstract":"Here we performed a single-cell RNA-Seq survey of 7,438 cells from 9 metastatic CRC patients, from whom matching adjacent normal tissues, primary tumors, and metastatic tumors were simultaneously sampled. Moreover, we also performed whole genome sequencing (WGS) on 81 sampled regions of these 9 patients and multi-region whole exome sequencing (WES) on 35 sample regions from 3 of these patients (patient #7-#9). We analyzed the dynamics of cell-type compositions, genomic copy number variants (CNVs), gene expression signatures, crosstalk between cancer cells and microenvironment cells and somatic mutations during CRC tumorigenesis and metastasis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003563","title":"Genetic Alterations in Benign Breast Biopsies of Subsequent Breast Cancer Patients","description":"Fibrocystic changes are associated with an increased risk of breast cancer (approximately 1.5-2 times that of the general population). Although the relative risk seems low, because of the high frequency of such changes, the absolute risk is significant. Genetic alterations have been found in fibrocystic changes with or without epithelial changes, suggesting that critical oncogenic events are occurring at an early stage. We investigated a unique collective of 17 breast cancer patients who, prior to the diagnosis of invasive breast cancer, underwent open surgical biopsy showing fibrocystic changes of the breast. Massive parallel sequencing targeting genes frequently mutated in breast cancer was performed on the fibrocystic breast tissue as well as the ensuing cancer tissue.","abstract":"Fibrocystic changes are associated with an increased risk of breast cancer (approximately 1.5-2 times that of the general population). Although the relative risk seems low, because of the high frequency of such changes, the absolute risk is significant. Genetic alterations have been found in fibrocystic changes with or without epithelial changes, suggesting that critical oncogenic events are occurring at an early stage. We investigated a unique collective of 17 breast cancer patients who, prior to the diagnosis of invasive breast cancer, underwent open surgical biopsy showing fibrocystic changes of the breast. Massive parallel sequencing targeting genes frequently mutated in breast cancer was performed on the fibrocystic breast tissue as well as the ensuing cancer tissue.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-29T10:12:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003564","title":"Probabilistic modeling of personalized drug combinations from integrated chemical screen and molecular data in sarcoma","description":"Background: Cancer patients with advanced disease exhaust available clinical regimens and lack actionable genomic medicine results, leaving a large patient population without effective treatments options when their disease inevitably progresses. To address the unmet clinical need for evidence-based therapy assignment when standard clinical approaches have failed, we have developed a probabilistic computational modeling approach which integrates sequencing data with functional assay data to develop patient-specific combination cancer treatments. Methods: Tissue taken from a murine model of alveolar rhabdomyosarcoma was used to perform single agent drug screening and DNA/RNA sequencing experiments; results integrated via our computational modeling approach identified a synergistic personalized two-drug combination. Cells derived from the tumor were allografted into mouse models and used to validate the personalized two-drug combination. Computational modeling of single agent drug screening and RNA sequencing of multiple heterogenous sites from a single patient’s epithelioid sarcoma identified a personalized two-drug combination effective across all tumor regions. The heterogeneity-consensus combination was validated in a xenograft model derived from the patient’s primary tumor. Cell cultures derived from human and canine undifferentiated pleomorphic sarcoma were assayed by drug screen; computational modeling identified a resistance-abrogating two-drug combination common to both cell cultures. This combination was validated in vitro via a cell regrowth assay.\nResults\nOur computational modeling approach addresses three major challenges in personalized cancer therapy: synergistic drug combination predictions (validated in vitro and in vivo in a genetically engineered murine cancer model), identification of unifying therapeutic targets to overcome intra-tumor heterogeneity (validated in vivo in a human cancer xenograft), and mitigation of cancer cell resistance and rewiring mechanisms (validated in vitro in a human and canine cancer model). \nConclusions\nThese proof-of-concept studies support the use of an integrative functional approach to personalized combination therapy prediction for the population of high-risk cancer patients lacking viable clinical options and without actionable DNA sequencing-based therapy.","abstract":"Background: Cancer patients with advanced disease exhaust available clinical regimens and lack actionable genomic medicine results, leaving a large patient population without effective treatments options when their disease inevitably progresses. To address the unmet clinical need for evidence-based therapy assignment when standard clinical approaches have failed, we have developed a probabilistic computational modeling approach which integrates sequencing data with functional assay data to develop patient-specific combination cancer treatments. Methods: Tissue taken from a murine model of alveolar rhabdomyosarcoma was used to perform single agent drug screening and DNA/RNA sequencing experiments; results integrated via our computational modeling approach identified a synergistic personalized two-drug combination. Cells derived from the tumor were allografted into mouse models and used to validate the personalized two-drug combination. Computational modeling of single agent drug screening and RNA sequencing of multiple heterogenous sites from a single patient’s epithelioid sarcoma identified a personalized two-drug combination effective across all tumor regions. The heterogeneity-consensus combination was validated in a xenograft model derived from the patient’s primary tumor. Cell cultures derived from human and canine undifferentiated pleomorphic sarcoma were assayed by drug screen; computational modeling identified a resistance-abrogating two-drug combination common to both cell cultures. This combination was validated in vitro via a cell regrowth assay.\nResults\nOur computational modeling approach addresses three major challenges in personalized cancer therapy: synergistic drug combination predictions (validated in vitro and in vivo in a genetically engineered murine cancer model), identification of unifying therapeutic targets to overcome intra-tumor heterogeneity (validated in vivo in a human cancer xenograft), and mitigation of cancer cell resistance and rewiring mechanisms (validated in vitro in a human and canine cancer model). \nConclusions\nThese proof-of-concept studies support the use of an integrative functional approach to personalized combination therapy prediction for the population of high-risk cancer patients lacking viable clinical options and without actionable DNA sequencing-based therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-03-30T21:47:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003565","title":"South Asia Rheumatic Heart Disease Genetics Network","description":"Rheumatic heart disease (RHD) is a major cause of cardiovascular death and disability amongst young adults. Building on a sample collection established for and genotyped in several earlier successful candidate gene studies, this case-control study investigated host genetic susceptibility to RHD using a genome-wide approach. The current dataset comprises over 850 individuals recruited in Uttar Pradesh, India, including cases of RHD based on echocardiographic diagnosis and controls recruited on the basis of normal echocardiograms. For this analysis all available samples were genotyped using the Illumina HumanCore-24 BeadChip platform. Efforts are now underway to establish new sample collections in other areas of India as well as Pakistan and later other neighbouring countries.","abstract":"Rheumatic heart disease (RHD) is a major cause of cardiovascular death and disability amongst young adults. Building on a sample collection established for and genotyped in several earlier successful candidate gene studies, this case-control study investigated host genetic susceptibility to RHD using a genome-wide approach. The current dataset comprises over 850 individuals recruited in Uttar Pradesh, India, including cases of RHD based on echocardiographic diagnosis and controls recruited on the basis of normal echocardiograms. For this analysis all available samples were genotyped using the Illumina HumanCore-24 BeadChip platform. Efforts are now underway to establish new sample collections in other areas of India as well as Pakistan and later other neighbouring countries.","study_type":"Other","pubmed_ids":[23749169,24797343,25273327,27118427],"external_links":null,"is_released":true,"released_date":"2019-04-01T11:45:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003566","title":"Functional differences between EBV- and CMV-specific CD8+ T cells demonstrate heterogeneity of T cell dysfunction in CLL","description":null,"abstract":"Chronic lymphocytic leukemia (CLL) is characterized by dysfunctional T cells. We studied T cell dysfunction by comparing isolated virus-specific CD8 T cells directed against CMV or EBV in both healthy controls and CLL patients. EBV-specific T cells of CLL patients show decreased functionality (especially on the cytotoxic level), whereas CMV-specific T cells are fully functional. Comparison of these two subsets can therefore shed light on the determinants of T cell dysfunction within the CLL micro-environment.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003567","title":"RNA_sequencing_of_CHD1L_knock_out_jurkat_clones","description":"In a recent meta-analysis of GWAS conducted in Africa, we and collaborators identified a novel population specific signal associated with HIV viral load (VL) among untreated HIV infected individuals. This variant is absent in Europeans, and has a frequency varying between 3.6% and 12.6% among Africans. The variant is located within a long intergenic noncoding RNA (LINC00624), which lies between the protein coding genes CHD1L and BLC9 and appears to be in high linkage disequilibrium (LD) with a splice site 1bp insertion at the start of exon 6 of the CHD1L gene. In a first round of experiments we generated CRISPR homozygous and heterozygotes frame shift knockouts (KO) of CHD1L from KOS iPSC lines. Viral infection experiments on these clones, after differentiation into macrophages, support a role for CHD1L in viral replication with higher viral activity observed in homozygotes KO. For the next set of experiments, we have generated CRISPR homozygous and heterozygotes CHD1L KO from an immortalized line of T lymphocytes (Jurkat, Clone E6-1). Total RNA sequencing as well as Western blots will be carried out in Jurkat clones to confirm the lack of gene product in knockout clones in comparison with wild type clones.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We have generated CRISPR homozygous and heterozygotes frame shift knockouts of CHD1L from an immortalized line of T lymphocytes (Jurkat, Clone E6-1). Total RNA sequencing as well as Western blots have been carried out in two independent homozygotes clones, one heterozygote and one wild type to confirm the lack of gene product in knockout clones in comparison with wild type clones. In parallel, we used the total RNA sequencing data also to investigate differences in gene expression profiles, including isoforms, among clones.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003568","title":"Multi-region sequencing of metastatic colorectal cancer","description":null,"abstract":"In order to reconstruct the evolutionary history of metastatic colorectal cancer, we performed whole-exome sequencing of 12 metastatic colorectal cancer patients for whom the primary tumor and matched distant metastases to the brain (n=10), liver (n=3), lung (n=1), as well as lymph node metastases (n=4) were available. For 8 of the 12 patients, multiple regions (n=3-8) of the primary tumor and distant metastases were sequenced.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003569","title":"mtDNA","description":"mtDNA","abstract":"mtDNA","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003570","title":"Whole-genome sequencing of normal Singaporean volunteers","description":null,"abstract":"Despite growing adoption of consumer wearables, the potential for sleep metrics from these devices to contribute to sleep-related biomedical research remains largely uncharacterized. Here we analyze sleep tracking data, along with questionnaire responses and multi-modal phenotypic data, generated from 482 normal volunteers. First, we provide a detailed comparison of wearable-derived and self-reported sleep metrics, particularly total sleep time (TST) and sleep efficiency (SE). We then identified demographic, socioeconomic and lifestyle factors associated with wearable-derived sleep duration. We also analyzed our multi-modal phenotypic data and showed that wearable-derived TST and SE are associated with various cardiovascular disease risk markers, whereas self-reported measures were not. Using whole- genome sequencing data, we estimated leukocyte telomere length and showed that volunteers with insufficient sleep also exhibit premature telomere attrition. Our study highlights the potential for sleep metrics generated by consumer wearables to provide novel insights into data generated from population cohort studies.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-03T12:07:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003571","title":"Understanding_Self__Organising_Capacity_of_Stem_Cells_during_Implantation_and_Early_Post_implantation_Development_in_vitro_and_in_vivo__Implications_for_Human_Development_","description":"The aim of this project is to differentiate human embryonic stem cells to an extra-embryonic fate, specifically the hypoblast. This is of uttermost importance given the current lack of human hypoblast stem cells. \n\nWe hypothesized that the pluripotent characteristics of the starting human embryonic stem cell population may dictate the competency for extra-embryonic cell fate specification. Based on this hypothesis and using human embryonic stem cells maintained in different naïve-like culture regimes, we have now developed conditions that allow the differentiation of human embryonic stem cells to a stable GATA6+ SOX2- population. This suggests that these cells may be putative human hypoblast stem cells. To validate this finding here we propose to perform RNA sequencing experiments of the differentiated human embryonic stem cells. By comparing their RNA expression profile to the single cell sequencing data of the human embryo that we are currently generating, we will be able to determine the identity of our GATA6+ SOX2- cells, and establish whether they represent the in vivo human hypoblast.","abstract":"The aim of this project is to differentiate human embryonic stem cells to an extra-embryonic fate, specifically the hypoblast. This is of uttermost importance given the current lack of human hypoblast stem cells. \n\nWe hypothesized that the pluripotent characteristics of the starting human embryonic stem cell population may dictate the competency for extra-embryonic cell fate specification. Based on this hypothesis and using human embryonic stem cells maintained in different naïve-like culture regimes, we have now developed conditions that allow the differentiation of human embryonic stem cells to a stable GATA6+ SOX2- population. This suggests that these cells may be putative human hypoblast stem cells. To validate this finding here we propose to perform RNA sequencing experiments of the differentiated human embryonic stem cells. By comparing their RNA expression profile to the single cell sequencing data of the human embryo that we are currently generating, we will be able to determine the identity of our GATA6+ SOX2- cells, and establish whether they represent the in vivo human hypoblast.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-03T11:14:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003572","title":"Pervasive H3K27 acetylation and ERV expression in H3.3K27M gliomas present a therapeutic vulnerability","description":"High-grade gliomas (HGG) defined by histone 3 K27M driver mutations exhibit global loss of H3K27 trimethylation and reciprocal gain of H3K27 acetylation, respectively shaping repressive and active chromatin landscapes. We generated tumor-derived isogenic models bearing this mutation and show that it leads to pervasive H3K27ac deposition across the genome. In turn, active enhancers and promoters are not created de novo and instead reflect the epigenomic landscape of the cell of origin. H3K27ac is enriched at repeat elements, resulting in their increased expression, which in turn can be further amplified by DNA demethylation and histone deacetylase inhibitors providing an exquisite therapeutic vulnerability. These agents may therefore modulate anti-tumor immune responses as a therapeutic modality for this untreatable disease.","abstract":"High-grade gliomas (HGG) defined by histone 3 K27M driver mutations exhibit global loss of H3K27 trimethylation and reciprocal gain of H3K27 acetylation, respectively shaping repressive and active chromatin landscapes. We generated tumor-derived isogenic models bearing this mutation and show that it leads to pervasive H3K27ac deposition across the genome. In turn, active enhancers and promoters are not created de novo and instead reflect the epigenomic landscape of the cell of origin. H3K27ac is enriched at repeat elements, resulting in their increased expression, which in turn can be further amplified by DNA demethylation and histone deacetylase inhibitors providing an exquisite therapeutic vulnerability. These agents may therefore modulate anti-tumor immune responses as a therapeutic modality for this untreatable disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-03T20:58:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003573","title":"Multi-Region WES of Metastatic Colorectal Cancer","description":null,"abstract":"In order to reconstruct the evolutionary history of metastatic colorectal cancer, we performed whole-exome sequencing of 12 metastatic colorectal cancer patients for whom the primary tumor and matched distant metastases to the brain (n=10) and liver (n=2) were available. For 8 of the 12 patients, multiple regions (n=3-7) of the primary tumor and distant metastases were sequenced.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-03T22:07:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003574","title":"Whole genome sequencing with linked reads for pediatric glioblastoma samples","description":null,"abstract":"Whole genome sequencing (WGS) with linked reads of pediatric glioblastoma (pGBM) samples from 8 patients. Diagnostic-recurrent pairs are available for 4 patients. Diagnostic sample and 3 recurrences are available for one patient. WGS with linked reads was also performed on the germlines (peripheral blood) of both parents of two pGBM patients.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003575","title":"RNA-sequencing of adult T-cell leukemia/lymphoma samples","description":"Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive hematological malignancy derived from mature CD4+ T-lymphocytes.  In this study, we performed RNA-sequencing (RNA-seq) analysis for ATL samples including 9 primary tumors and 1 ATL cell line to clarify gene expression profiles in this disease.","abstract":"Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive hematological malignancy derived from mature CD4+ T-lymphocytes.  In this study, we performed RNA-sequencing (RNA-seq) analysis for ATL samples including 9 primary tumors and 1 ATL cell line to clarify gene expression profiles in this disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-04T10:48:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003576","title":"Cancer-Associated Mutations in Endometriosis without Cancer","description":"Endometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% of reproductive-age women and can cause pelvic pain and infertility. Endometriotic lesions are considered to be benign inflammatory lesions but have cancerlike features such as local invasion and resistance to apoptosis","abstract":"Endometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% of reproductive-age women and can cause pelvic pain and infertility. Endometriotic lesions are considered to be benign inflammatory lesions but have cancerlike features such as local invasion and resistance to apoptosis","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-04T21:13:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003577","title":"RNASeq_of_mouse_DDD_models_Y3","description":"We are continuing our QQ work to identify the molecular underpinnings of human developmental disorders identified in the DDD project. To do this, we are carrying out RNA sequencing in mouse models of disease, particularly those affecting chromatin modifying proteins.                                                                                                 We are performing RNAseq on adult brain sub-regions known to be important in learning and memory. We are also performing RNAseq on brain tissue from foetal timepoints, to examine the impact of these mutations on prenatal eurodevelopment. This will allow us to distinguish early effects in neurodevelopment and late effects on normal brain function, identifying critical timepoints in these disorders and the transcriptional changes underlying these disorders.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We are continuing our QQ work to identify the molecular underpinnings of human developmental disorders identified in the DDD project. To do this, we are carrying out RNA sequencing in mouse models of disease, particularly those affecting chromatin modifying proteins.                                                                                                 We are performing RNAseq on adult brain sub-regions known to be important in learning and memory. We are also performing RNAseq on brain tissue from foetal timepoints, to examine the impact of these mutations on prenatal eurodevelopment. This will allow us to distinguish early effects in neurodevelopment and late effects on normal brain function, identifying critical timepoints in these disorders and the transcriptional changes underlying these disorders.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003578","title":"HG_evaluation_of_DNA_modifications_correlated_with_the_NSD1_associated_methylation_using_Oxford_Nanopore_sequencing","description":"A large subset of the DDD cohort has pathogenic de novo mutations in genes that encode machinery that modify and re-model chromatin. Many of these Chromatin Modifying Genes (CMG) genes are broadly expressed, including in accessible tissue(s) that have been sampled from the affected offspring (blood and saliva). Previously, it has been shown by us and others that many of these CMG gene disorders also possess a distinct methylation signature shared by pathogenic variants, and that these signatures can potentially be discriminating enough to inform diagnosis of new cases, especially of Variants of Uncertain Significance (VUS). Handsaker’s PhD project has validated a previously published NSD1 methylation signature and has confirmed that this signature is robust and reliable across different methylation arrays and sites. Thus far, this signature has been validated using the Illumina EPIC (850K) methylation array run at Sanger, and Illumina 450K array data generated by Rosanna Weksberg’s group, in Toronto. Juliet has shown that the NSD1 methylation signature can be detected ab initio with as few as 5 probands and 6 negative controls.                                                                                                                                                  In the proposed project, DNA derived from whole blood from 5 probands with a confirmed pathogenic de novo NSD1 variant and 6 negative controls will be Oxford Nanopore sequenced with the purpose of calling both the pathogenic DNA variant and identifying the established methylation signature in a single readout. Negative controls will be chosen from a set of DDD probands with pathogenic mutations in a gene not expressed in blood and control methylation status validated on the EPIC array. We will also include an additional proband suspected on the basis of clinical phenotype to have Sotos syndrome (caused by mutations in NSD1) with a de novo synonymous variant predicted to disrupt splicing. We are aiming to generate ~30X genome coverage per sample.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"A large subset of the DDD cohort has pathogenic de novo mutations in genes that encode machinery that modify and re-model chromatin. Many of these Chromatin Modifying Genes (CMG) genes are broadly expressed, including in accessible tissue(s) that have been sampled from the affected offspring (blood and saliva). Previously, it has been shown by us and others that many of these CMG gene disorders also possess a distinct methylation signature shared by pathogenic variants, and that these signatures can potentially be discriminating enough to inform diagnosis of new cases, especially of Variants of Uncertain Significance (VUS). Handsaker’s PhD project has validated a previously published NSD1 methylation signature and has confirmed that this signature is robust and reliable across different methylation arrays and sites. Thus far, this signature has been validated using the Illumina EPIC (850K) methylation array run at Sanger, and Illumina 450K array data generated by Rosanna Weksberg’s group, in Toronto. Juliet has shown that the NSD1 methylation signature can be detected ab initio with as few as 5 probands and 6 negative controls.                                                                                                                                                  In the proposed project, DNA derived from whole blood from 5 probands with a confirmed pathogenic de novo NSD1 variant and 6 negative controls will be Oxford Nanopore sequenced with the purpose of calling both the pathogenic DNA variant and identifying the established methylation signature in a single readout. Negative controls will be chosen from a set of DDD probands with pathogenic mutations in a gene not expressed in blood and control methylation status validated on the EPIC array. We will also include an additional proband suspected on the basis of clinical phenotype to have Sotos syndrome (caused by mutations in NSD1) with a de novo synonymous variant predicted to disrupt splicing. We are aiming to generate ~30X genome coverage per sample.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003579","title":"Analysis of four key cell types (epithelial, fbroblast, myeloid and T cells)","description":"Alterations of the normal prostate epithelial cell genome trigger the emergence of carcinoma, however cancer-only analyses of genomic aberrations have resulted in little clinical translation. A deep understanding of the tumor microenvironment is likely to inform  on key drivers of disease progression and novel therapeutic opportunities. We investigated the role of key cell types along disease progression, profiling the RNA abundance of 52 samples from 13 patients enriched for one of four key cell types, spanning a wide CAPRA-S risk score range.  Using a novel differential transcription Bayes method, TABI, we avoided a priori patient stratification, and mapped transcriptional alteration events to specific risk scores. The developmental and cell-type  resolution yielded a landscape of concurrent transcriptional alterations from the tumour microenvironment, including key hallmarks. These transcriptional signatures permitted the identification of a “high survival” patient cluster in an independent prostate cancer dataset. Most importantly, together with our integrated transcriptional analysis, differential tissue composition analysis provided evidence for a key role for monocytes and macrophages in prostate cancer progression and disease recurrence.","abstract":"Alterations of the normal prostate epithelial cell genome trigger the emergence of carcinoma, however cancer-only analyses of genomic aberrations have resulted in little clinical translation. A deep understanding of the tumor microenvironment is likely to inform  on key drivers of disease progression and novel therapeutic opportunities. We investigated the role of key cell types along disease progression, profiling the RNA abundance of 52 samples from 13 patients enriched for one of four key cell types, spanning a wide CAPRA-S risk score range.  Using a novel differential transcription Bayes method, TABI, we avoided a priori patient stratification, and mapped transcriptional alteration events to specific risk scores. The developmental and cell-type  resolution yielded a landscape of concurrent transcriptional alterations from the tumour microenvironment, including key hallmarks. These transcriptional signatures permitted the identification of a “high survival” patient cluster in an independent prostate cancer dataset. Most importantly, together with our integrated transcriptional analysis, differential tissue composition analysis provided evidence for a key role for monocytes and macrophages in prostate cancer progression and disease recurrence.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-05T15:42:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003580","title":"Single Cell Dissection of Nasopharyngeal Carcinoma","description":null,"abstract":"Nasopharyngeal carcinoma (NPC), a heterogeneous epithelial tumor with heavy lymphocyte infiltration, is the most common head and neck cancer in southeast Asia. Efforts to identify prognostic markers and potential therapeutic targets have been hampered by the poor understanding of its cellular heterogeneity. Here, we applied single-cell RNA sequencing to comprehensively evaluate the multicellular ecosystem of 15 primary NPC tumors; ; the normal nasopharyngeal epithelial tissue from one patient with chronic nasopharyngitis was also collected as a control. We also acquired bulk WES and RNA-seq data for 12 tumors. represents an important step toward understanding the cellular ecosystem in the tumor microenvironment of NPC and identifies novel prognostic signatures and potential targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003581","title":"Single Cell Dissection of Nasopharyngeal Carcinoma","description":null,"abstract":"Nasopharyngeal carcinoma (NPC), a heterogeneous epithelial tumor with heavy lymphocyte infiltration, is the most common head and neck cancer in southeast Asia. Efforts to identify prognostic markers and potential therapeutic targets have been hampered by the poor understanding of its cellular heterogeneity. Here, we applied single-cell RNA sequencing to comprehensively evaluate the multicellular ecosystem of 15 primary NPC tumors; ; the normal nasopharyngeal epithelial tissue from one patient with chronic nasopharyngitis was also collected as a control. We also acquired bulk WES and RNA-seq data for 12 tumors. represents an important step toward understanding the cellular ecosystem in the tumor microenvironment of NPC and identifies novel prognostic signatures and potential targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003582","title":"Phylogenetic evolution of metastatic melanoma.","description":"To explore molecular factors associated with evolution and resistance in melanoma evolution, we multi-lesion sequenced primary and metastatic sites collected from autopsy in seven patients.","abstract":"To explore molecular factors associated with evolution and resistance in melanoma evolution, we multi-lesion sequenced primary and metastatic sites collected from autopsy in seven patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-08T23:04:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003583","title":"Genetic dysregulation of gene expression and splicing during a ten-year period of human aging in the PIVUS study","description":"We performed RNA sequencing in whole-blood from the same individuals from the PIVUS study at ages 70 and 80 to quantify how gene expression, alternative splicing, and their genetic regulation are altered during this 10-year period of advanced aging.","abstract":"We performed RNA sequencing in whole-blood from the same individuals from the PIVUS study at ages 70 and 80 to quantify how gene expression, alternative splicing, and their genetic regulation are altered during this 10-year period of advanced aging.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-09T01:05:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003584","title":"Gene identification and functional analyses of unsolved patients with neuromuscular disorders","description":null,"abstract":"Introduction: Spinal muscular atrophy (SMA) without deletions/mutations in SMN1 (non-5q-SMA) is genetically very heterogeneous. Due to strongly overlapping phenotypes of neuromuscular disorders, the differential diagnosis of non-5q-SMAs is challenging. \nMaterials/Methods: For the last 23 years, we have performed SMN1 deletion analysis to 3,535 individuals with suspected SMA. In 1,715 (48.5%) of these individuals, no SMN1 deletion/mutation was detected. Review of the clinical data with respect to a possible motor neuron disorder led to 114 patients who were available and consented to participate. These 114 patients were analysed by two different gene panels. Of these, 24 unresolved patients and 49 new patients were analysed by WES or/and WGS. \nResults: Gene panel provided a diagnosis in 39% (44/114) of the probands. The neuromuscular disease panel with 479 genes outperformed the lower motor neuron disease panel with 62 genes with a 44% to 13% diagnostic yield, respectively. WES/WGS revealed the disease-causing mutation in 38% (28/73) of these patients. Within the NeurOmics project, we published five novel disease-causing genes (BICD2, CHP1, PIEZO2, VAMP1, ADPRHL2) and introduced three novel genes (PRUNE1, MCM3AP, AGTPBP1) with recently published overlapping phenotypes. \nDiscussion: NGS is a powerful method for diagnostic and gene identification purposes in non-5q-SMA, and illustrate the wide spectrum of neuromuscular disorders that initially present as motor neuron disease. Gene panels with larger gene representation perform best in clinical conditions with heterogenic genetic background. For phenotypes that are not fulfilling the core clinical criteria for motor neuron disorders, a more comprehensive WES or WGS methods should be used.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003585","title":"Gut microbiota analysis after 3months probiotic-like bacteria or placebo treatment in subjects with metabolic syndrome","description":"Background: Probiotic-like bacteria treatment has been described to be associated with gut microbiota modifications. Goal: To decipher if the effects of the tested probiotic-like bacteria are due to the bacteria itself or due to the effects of the bacteria on the gut microbiota. Methodology: In this study, gut microbiota has been analyzed from feces samples of subjects with metabolic syndrome and treated with one of the 2 tested probiotic-like bacteria or with the placebo during 3months.","abstract":"Background: Probiotic-like bacteria treatment has been described to be associated with gut microbiota modifications. Goal: To decipher if the effects of the tested probiotic-like bacteria are due to the bacteria itself or due to the effects of the bacteria on the gut microbiota. Methodology: In this study, gut microbiota has been analyzed from feces samples of subjects with metabolic syndrome and treated with one of the 2 tested probiotic-like bacteria or with the placebo during 3months.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-09T13:43:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003586","title":"Disease and phenotype relevant genetic variants identified from histone acetylomes in human hearts","description":"Identifying genetic markers for heterogeneous complex diseases such as heart failure has been challenging, and may require prohibitively large cohort sizes in genome-wide association studies (GWAS) in order to demonstrate statistical significance1. On the other hand, chromatin quantitative trait loci (QTL), elucidated by direct epigenetic profiling of specific human tissues, may contribute towards prioritising variants for disease-association. Here, we captured non-coding genetic variants by performing enhancer H3K27ac ChIP-seq in 70 human control and end-stage failing hearts, mapping out a comprehensive catalogue of 47,321 putative human heart enhancers. 3,897 differential acetylation peaks (FDR &lt; 0.05) pointed to recognizable pathways altered in heart failure (HF). To identify cardiac histone acetylation QTLs (haQTLs), we regressed out confounding factors including HF disease status, and employed the G-SCI test2 to call out 1,680 haQTLs (FDR &lt; 0.1). A subset of these showed significant association to gene expression, either in cis (180), or through long range interactions (81), identified by Hi-C and Hi-ChIP performed on a subset of hearts. Furthermore, a concordant relationship was found between the gain or disruption of specific transcription factor (TF) binding motifs, inferred from alternative alleles at the haQTLs, associated with altered H3K27ac peak heights. Finally, colocalisation of our haQTLs with heart-related GWAS datasets allowed us to identify 62 unique loci. Disease-association for these new loci may indeed be mediated through modification of H3K27-acetylation enrichment and their corresponding gene expression differences.","abstract":"Identifying genetic markers for heterogeneous complex diseases such as heart failure has been challenging, and may require prohibitively large cohort sizes in genome-wide association studies (GWAS) in order to demonstrate statistical significance1. On the other hand, chromatin quantitative trait loci (QTL), elucidated by direct epigenetic profiling of specific human tissues, may contribute towards prioritising variants for disease-association. Here, we captured non-coding genetic variants by performing enhancer H3K27ac ChIP-seq in 70 human control and end-stage failing hearts, mapping out a comprehensive catalogue of 47,321 putative human heart enhancers. 3,897 differential acetylation peaks (FDR &lt; 0.05) pointed to recognizable pathways altered in heart failure (HF). To identify cardiac histone acetylation QTLs (haQTLs), we regressed out confounding factors including HF disease status, and employed the G-SCI test2 to call out 1,680 haQTLs (FDR &lt; 0.1). A subset of these showed significant association to gene expression, either in cis (180), or through long range interactions (81), identified by Hi-C and Hi-ChIP performed on a subset of hearts. Furthermore, a concordant relationship was found between the gain or disruption of specific transcription factor (TF) binding motifs, inferred from alternative alleles at the haQTLs, associated with altered H3K27ac peak heights. Finally, colocalisation of our haQTLs with heart-related GWAS datasets allowed us to identify 62 unique loci. Disease-association for these new loci may indeed be mediated through modification of H3K27-acetylation enrichment and their corresponding gene expression differences.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-09T14:33:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003587","title":"Somatic_Mutations_in_Degenerative_Disease__WGS_","description":"The study will explore genetic changes (somatic mutations) that occur throughout life in human joints and in degenerative joint diseases. The data in this study will be generated by whole-genome sequencing of laser-dissected microbiopsies and bulk blood samples from the synovium of patients with a range of degenerative joint diseases.","abstract":"The study will explore genetic changes (somatic mutations) that occur throughout life in human joints and in degenerative joint diseases. The data in this study will be generated by whole-genome sequencing of laser-dissected microbiopsies and bulk blood samples from the synovium of patients with a range of degenerative joint diseases.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003588","title":"Somatic_Mutations_in_Degenerative_Disease__exome_","description":"The study will explore genetic changes (somatic mutations) that occur throughout life in human joints and in degenerative joint diseases. The data in this study will be generated by whole-exome sequencing of laser-dissected microbiopsies from the synovium of patients with a range of degenerative joint diseases.","abstract":"The study will explore genetic changes (somatic mutations) that occur throughout life in human joints and in degenerative joint diseases. The data in this study will be generated by whole-exome sequencing of laser-dissected microbiopsies from the synovium of patients with a range of degenerative joint diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003589","title":"Identification and characterization of disease-causing genes in non-5q-SMA by next-generation sequencing technology","description":"Introduction: Spinal muscular atrophy (SMA) without deletions/mutations in SMN1 (non-5q-SMA) is genetically very heterogeneous. Due to strongly overlapping phenotypes of neuromuscular disorders, the differential diagnosis of non-5q-SMAs is challenging. Materials/Methods: For the last 23 years, we have performed SMN1 deletion analysis to 3,535 individuals with suspected SMA. In 1,715 (48.5%) of these individuals, no SMN1 deletion/mutation was detected. Review of the clinical data with respect to a possible motor neuron disorder led to 114 patients who were available and consented to participate. These 114 patients were analysed by two different gene panels. Of these, 24 unresolved patients and 49 new patients were analysed by WES or/and WGS. Results: Gene panel provided a diagnosis in 39% (44/114) of the probands. The neuromuscular disease panel with 479 genes outperformed the lower motor neuron disease panel with 62 genes with a 44% to 13% diagnostic yield, respectively. WES/WGS revealed the disease-causing mutation in 38% (28/73) of these patients. Within the NeurOmics project, we published five novel disease-causing genes (BICD2, CHP1, PIEZO2, VAMP1, ADPRHL2) and introduced three novel genes (PRUNE1, MCM3AP, AGTPBP1) with recently published overlapping phenotypes. Discussion: NGS is a powerful method for diagnostic and gene identification purposes in non-5q-SMA, and illustrate the wide spectrum of neuromuscular disorders that initially present as motor neuron disease. Gene panels with larger gene representation perform best in clinical conditions with heterogenic genetic background. For phenotypes that are not fulfilling the core clinical criteria for motor neuron disorders, a more comprehensive WES or WGS methods should be used.","abstract":"Introduction: Spinal muscular atrophy (SMA) without deletions/mutations in SMN1 (non-5q-SMA) is genetically very heterogeneous. Due to strongly overlapping phenotypes of neuromuscular disorders, the differential diagnosis of non-5q-SMAs is challenging. Materials/Methods: For the last 23 years, we have performed SMN1 deletion analysis to 3,535 individuals with suspected SMA. In 1,715 (48.5%) of these individuals, no SMN1 deletion/mutation was detected. Review of the clinical data with respect to a possible motor neuron disorder led to 114 patients who were available and consented to participate. These 114 patients were analysed by two different gene panels. Of these, 24 unresolved patients and 49 new patients were analysed by WES or/and WGS. Results: Gene panel provided a diagnosis in 39% (44/114) of the probands. The neuromuscular disease panel with 479 genes outperformed the lower motor neuron disease panel with 62 genes with a 44% to 13% diagnostic yield, respectively. WES/WGS revealed the disease-causing mutation in 38% (28/73) of these patients. Within the NeurOmics project, we published five novel disease-causing genes (BICD2, CHP1, PIEZO2, VAMP1, ADPRHL2) and introduced three novel genes (PRUNE1, MCM3AP, AGTPBP1) with recently published overlapping phenotypes. Discussion: NGS is a powerful method for diagnostic and gene identification purposes in non-5q-SMA, and illustrate the wide spectrum of neuromuscular disorders that initially present as motor neuron disease. Gene panels with larger gene representation perform best in clinical conditions with heterogenic genetic background. For phenotypes that are not fulfilling the core clinical criteria for motor neuron disorders, a more comprehensive WES or WGS methods should be used.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003590","title":"Investigation of human variation in healthy individuals on gene and protein levels","description":"The study examines human variation in healthy individuals, with samples taken from peripheral blood mononuclear cells. The study is a part of a larger effort to understand variants better both on level of genes and proteins. Thus for each DNA sample, corresponding protein samples are available.","abstract":"The study examines human variation in healthy individuals, with samples taken from peripheral blood mononuclear cells. The study is a part of a larger effort to understand variants better both on level of genes and proteins. Thus for each DNA sample, corresponding protein samples are available.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-10T11:46:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003591","title":"Circadian Clock Properties in Type 2 Diabetic Patients","description":"The circadian system plays an essential role in regulating timing of body metabolism in humans. Indeed, circadian misalignments are strongly associated with high rates of metabolic disorders. Molecular makeup of the circadian oscillator can be deciphered in cells cultured in vitro, and these cellular rhythms are highly informative of the physiological circadian rhythm in vivo.We aimed at assessing molecular clock properties in dermal fibroblasts established from the skin biopsies of seventeen Type 2 diabetic obese and non-obese patients and eleven healthy controls. Following in vitro synchronization, primary fibroblast cultures were subjected to continuous assessment of circadian bioluminescence profiles based on lentiviral luciferase reporters. We observed a strong inverse correlation between HbA1c values and circadian period length within cells from the Type 2 diabetic group. RNA sequencing analysis conducted in this group samples revealed that ICAM1 encoding for the endothelial adhesion protein was differentially expressed between Type 2 diabetic compensated and non-compensated fibroblasts, and correlated with the period length. Furthermore, ICAM1 expression is driven by rhythmic CLOCK binding. We provide for the first time a potential molecular link between severity of Type 2 diabetes and circadian clock machinery, which paves a way for further mechanistic understanding of circadian oscillator changes upon Type 2 diabetes in humans.","abstract":"The circadian system plays an essential role in regulating timing of body metabolism in humans. Indeed, circadian misalignments are strongly associated with high rates of metabolic disorders. Molecular makeup of the circadian oscillator can be deciphered in cells cultured in vitro, and these cellular rhythms are highly informative of the physiological circadian rhythm in vivo.We aimed at assessing molecular clock properties in dermal fibroblasts established from the skin biopsies of seventeen Type 2 diabetic obese and non-obese patients and eleven healthy controls. Following in vitro synchronization, primary fibroblast cultures were subjected to continuous assessment of circadian bioluminescence profiles based on lentiviral luciferase reporters. We observed a strong inverse correlation between HbA1c values and circadian period length within cells from the Type 2 diabetic group. RNA sequencing analysis conducted in this group samples revealed that ICAM1 encoding for the endothelial adhesion protein was differentially expressed between Type 2 diabetic compensated and non-compensated fibroblasts, and correlated with the period length. Furthermore, ICAM1 expression is driven by rhythmic CLOCK binding. We provide for the first time a potential molecular link between severity of Type 2 diabetes and circadian clock machinery, which paves a way for further mechanistic understanding of circadian oscillator changes upon Type 2 diabetes in humans.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003592","title":"5- FU treated organoids","description":"5-Fluorouracil (5-FU) is a chemotherapeutic drug component that is commonly used for the treatment of solid cancers. The anticancer properties of 5-FU have been attributed to interference with nucleotide synthesis and through direct incorporation into the DNA as being a pyrimidine analog. As both mechanisms of action may have a mutational impact on surviving tumor cells, we performed three independent analyses to characterize the genomic consequences of 5-FU treatment: i) in vitro treatment of intestinal organoids with 5-FU followed by whole genome sequencing, ii) genome-wide mutation analyses in tumor samples from 5-FU treated patients with breast or colorectal cancer, and iii) analysis of paired biopsies from patients treated with 5-FU between biopsies. Our results demonstrate that both in vitro and in vivo 5-FU causes a mutational pattern that is dominated by T&gt;G substitutions in a CTT context and with strong resemblance to COSMIC signature 17. Interestingly, this signature is also found in non 5-FU treated patients, most prominently in esophageal tumors, indicating that distinct endogenous and exogenous triggers can converge into highly similar mutational signatures. Furthermore, our results suggest that 5-FU may have adverse mutagenic effects on healthy cells and contributes to genetic variability in surviving cancer cells thereby contributing to tumor evolution.","abstract":"5-Fluorouracil (5-FU) is a chemotherapeutic drug component that is commonly used for the treatment of solid cancers. The anticancer properties of 5-FU have been attributed to interference with nucleotide synthesis and through direct incorporation into the DNA as being a pyrimidine analog. As both mechanisms of action may have a mutational impact on surviving tumor cells, we performed three independent analyses to characterize the genomic consequences of 5-FU treatment: i) in vitro treatment of intestinal organoids with 5-FU followed by whole genome sequencing, ii) genome-wide mutation analyses in tumor samples from 5-FU treated patients with breast or colorectal cancer, and iii) analysis of paired biopsies from patients treated with 5-FU between biopsies. Our results demonstrate that both in vitro and in vivo 5-FU causes a mutational pattern that is dominated by T&gt;G substitutions in a CTT context and with strong resemblance to COSMIC signature 17. Interestingly, this signature is also found in non 5-FU treated patients, most prominently in esophageal tumors, indicating that distinct endogenous and exogenous triggers can converge into highly similar mutational signatures. Furthermore, our results suggest that 5-FU may have adverse mutagenic effects on healthy cells and contributes to genetic variability in surviving cancer cells thereby contributing to tumor evolution.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-12T10:09:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003593","title":"Plasma miRNA before and after weight loss","description":null,"abstract":"Diet induced weight loss represents an intervention for obesity to prevent associated diseases. However there is considerable inter-individual variation in the response to weight loss. Single nucleotide polymorphisms (SNPs) and plasma miRNA might be contributing factors. We therefore hypothesized that changes in the miRNA pattern during weight loss depend on the SNP genotype.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003594","title":"Lymphocyte_Gut_WGS_H38","description":"We study lymphocyte somatic evolution through the sequencing of normal healthy lymphocytes. We perform whole-genome sequencing of single-cell derived T and B cell colonies to identify somatic mutations, and perform targeted deep-sequencing of these mutations. The lineages of T and B cells, and the frequencies of these mutations reveals the neutral and non-neutral evolutionary processes underlying lymphocyte growth and function.","abstract":"As we age, our cells accumulate mutations, termed \"somatic mutations\". Somatic mutations, which exist in mosaic form throughout the body, are a direct record of the evolution of our cells. Some of these mutations are subject to neutral evolution. The study of neutral mutations can reveal the cell lineages resulting from normal development and tissue maintenance, and help us understand key demographic parameter of somatic evolution, such as population size and migration. Other mutations are under selection, resulting in the expansion or contraction of lineages. These mutations can lead to disease, such as cancer; however, the extent of selection on somatic mutations in not understood. We aim to understand the somatic evolution of the primary cells of the adaptive immune system, lymphocytes. As we age, lymphocytes accumulate somatic mutations, which reveal the evolutionary history of lymphocytes, as well as providing information about the particular mutations and lineage structures that contribute to age-related immune disorder. In order to understand somatic evolution in lymphocytes, we sequence lymphocytes from normal, healthy individuals across a range of ages. We perform whole-genome sequencing of single-cell derived T and B cell colonies to identify somatic mutations, and perform targeted deep-sequencing of these mutations. The lineages of T and B cells, and the frequencies of these mutations reveals the neutral and non-neutral evolutionary processes underlying lymphocyte growth.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-12T13:39:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003595","title":"Lymphocyte_colony_WGS_H38","description":"We study lymphocyte somatic evolution through the sequencing of normal healthy lymphocytes. We perform whole-genome sequencing of single-cell derived T and B cell colonies to identify somatic mutations, and perform targeted deep-sequencing of these mutations. The lineages of T and B cells, and the frequencies of these mutations reveals the neutral and non-neutral evolutionary processes underlying lymphocyte growth and function.","abstract":"As we age, our cells accumulate mutations, termed \"somatic mutations\". Somatic mutations, which exist in mosaic form throughout the body, are a direct record of the evolution of our cells. Some of these mutations are subject to neutral evolution. The study of neutral mutations can reveal the cell lineages resulting from normal development and tissue maintenance, and help us understand key demographic parameter of somatic evolution, such as population size and migration. Other mutations are under selection, resulting in the expansion or contraction of lineages. These mutations can lead to disease, such as cancer; however, the extent of selection on somatic mutations in not understood. We aim to understand the somatic evolution of the primary cells of the adaptive immune system, lymphocytes. As we age, lymphocytes accumulate somatic mutations, which reveal the evolutionary history of lymphocytes, as well as providing information about the particular mutations and lineage structures that contribute to age-related immune disorder. In order to understand somatic evolution in lymphocytes, we sequence lymphocytes from normal, healthy individuals across a range of ages. We perform whole-genome sequencing of single-cell derived T and B cell colonies to identify somatic mutations, and perform targeted deep-sequencing of these mutations. The lineages of T and B cells, and the frequencies of these mutations reveals the neutral and non-neutral evolutionary processes underlying lymphocyte growth.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003596","title":"Lymphocyte_PanBody_WGS_H38","description":"We study lymphocyte somatic evolution through the sequencing of normal healthy lymphocytes. We perform whole-genome sequencing of single-cell derived T and B cell colonies to identify somatic mutations, and perform targeted deep-sequencing of these mutations. The lineages of T and B cells, and the frequencies of these mutations reveals the neutral and non-neutral evolutionary processes underlying lymphocyte growth and function.","abstract":"As we age, our cells accumulate mutations, termed \"somatic mutations\". Somatic mutations, which exist in mosaic form throughout the body, are a direct record of the evolution of our cells. Some of these mutations are subject to neutral evolution. The study of neutral mutations can reveal the cell lineages resulting from normal development and tissue maintenance, and help us understand key demographic parameter of somatic evolution, such as population size and migration. Other mutations are under selection, resulting in the expansion or contraction of lineages. These mutations can lead to disease, such as cancer; however, the extent of selection on somatic mutations in not understood. We aim to understand the somatic evolution of the primary cells of the adaptive immune system, lymphocytes. As we age, lymphocytes accumulate somatic mutations, which reveal the evolutionary history of lymphocytes, as well as providing information about the particular mutations and lineage structures that contribute to age-related immune disorder. In order to understand somatic evolution in lymphocytes, we sequence lymphocytes from normal, healthy individuals across a range of ages. We perform whole-genome sequencing of single-cell derived T and B cell colonies to identify somatic mutations, and perform targeted deep-sequencing of these mutations. The lineages of T and B cells, and the frequencies of these mutations reveals the neutral and non-neutral evolutionary processes underlying lymphocyte growth.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-12T13:45:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003597","title":"Genetic landscape of Waldenstrom macroglobulinemia","description":null,"abstract":"Exome analyses for the identification of somatic mutation in Waldenstrom macroglobulinemia by comparison of tumor and  CD3+(germ line control) population in 16 patients.\ntranscription profiling of a series of Waldenstrom macroglobulinemia samples","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003598","title":"Single cell transcriptomic and genomic profiling of carcinogenesis in patients with familial adenomatous polyposis","description":"Familial Adenomatous Polyposis (FAP) is characterized by hundreds to thousands of adenocarcinomas at different evolutional stages in the colon and rectum. Much effort has been made to illuminate the key genomic alterations that facilitate the transition from adenoma to carcinoma. However, the strong heterogeneity of the tumors may hamper these efforts. Here, by sequencing matched adjacent normal tissues, adenomas at different stages and carcinomas from the same patient, we precisely traced the process of colorectal carcinogenesis. Our study offers an accurate genomic landscape during the initiation and progression of carcinogenesis, especially for the transition between adenomas and carcinomas.","abstract":"Familial Adenomatous Polyposis (FAP) is characterized by hundreds to thousands of adenocarcinomas at different evolutional stages in the colon and rectum. Much effort has been made to illuminate the key genomic alterations that facilitate the transition from adenoma to carcinoma. However, the strong heterogeneity of the tumors may hamper these efforts. Here, by sequencing matched adjacent normal tissues, adenomas at different stages and carcinomas from the same patient, we precisely traced the process of colorectal carcinogenesis. Our study offers an accurate genomic landscape during the initiation and progression of carcinogenesis, especially for the transition between adenomas and carcinomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-15T02:41:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003599","title":"Whole exome sequencing of trio with primary immunodeficiency (IL2RB)","description":"A novel homozygous mutation in human IL2RB results in decreased IL-2RB protein expression and dysregulated IL-2/15 signaling. This hypomorphic mutation leads to decreased regulatory T cell frequency and abnormal NK cell compartment, with clinical manifestations of autoimmunity and susceptibility to CMV.","abstract":"A novel homozygous mutation in human IL2RB results in decreased IL-2RB protein expression and dysregulated IL-2/15 signaling. This hypomorphic mutation leads to decreased regulatory T cell frequency and abnormal NK cell compartment, with clinical manifestations of autoimmunity and susceptibility to CMV.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-15T15:52:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003600","title":"Quantitative microbiome profiling disentangles inflammation- and bile duct obstruction-associated microbiota alterations across IBD/PSC diagnoses","description":"Disease-association microbiome dataset comprising 106 primary sclerosing cholangitis and/or inflammatory bowel disease (PSC/IBD) patients. Assessing quantitative taxon abundances, we study microbiome alterations beyond symptomatic stool moisture variation. We observe a high prevalence of a low cell count Bacteroides2 enterotype across patient groups when compared to healthy controls, with microbial loads correlating inversely with intestinal and systemic inflammation markers. Quantitative analyses allow us to differentiate between taxa associated to either intestinal inflammation severity (Fusobacterium) or cholangitis/biliary obstruction (Enterococcus) among previously suggested PSC marker genera. We identify and validate a near-exclusion pattern between the inflammation-associated Fusobacterium and Veillonella genera, with Fusobacterium detection being restricted to Crohn’s disease (CD) and PSC-CD patients. Overall, through absolute quantification and confounder control, we single out clear-cut microbiome markers associated to pathophysiological manifestations and disease diagnosis.","abstract":"Disease-association microbiome dataset comprising 106 primary sclerosing cholangitis and/or inflammatory bowel disease (PSC/IBD) patients. Assessing quantitative taxon abundances, we study microbiome alterations beyond symptomatic stool moisture variation. We observe a high prevalence of a low cell count Bacteroides2 enterotype across patient groups when compared to healthy controls, with microbial loads correlating inversely with intestinal and systemic inflammation markers. Quantitative analyses allow us to differentiate between taxa associated to either intestinal inflammation severity (Fusobacterium) or cholangitis/biliary obstruction (Enterococcus) among previously suggested PSC marker genera. We identify and validate a near-exclusion pattern between the inflammation-associated Fusobacterium and Veillonella genera, with Fusobacterium detection being restricted to Crohn’s disease (CD) and PSC-CD patients. Overall, through absolute quantification and confounder control, we single out clear-cut microbiome markers associated to pathophysiological manifestations and disease diagnosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-16T16:14:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003601","title":"Dedifferentiated_Melanoma_RNAseq","description":"De- and transdifferentiation of melanoma is a rare histopathological phenomenon that has not be characterised genetically. In this project we plan to sequence the genomes of de and transdifferentiated cases so as to define their genetic make-up.","abstract":"De- and transdifferentiation of melanoma is a rare histopathological phenomenon that has not be characterised genetically. In this project we plan to sequence the genomes of de and transdifferentiated cases so as to define their genetic make-up.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-17T11:09:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003602","title":"GDAP___Genome_Diversity_in_Africa_Project","description":"The Genomic Diversity in Africa Project (GDAP) started with the plan to develop a genomic resource from African populations, characterise genomic diversity and population history, and facilitate clinical studies in Africa. Currently, 25 individuals from 24 ethnolinguistic groups have been whole-genome sequenced at high depth totalling 585 individuals. An additional 41 individuals have been sequenced with 10X Genomics libraries. At this stage, the initial curation of this dataset has been finished and we are performing the analysis in coordination with our collaborators. The current state of the GDAP represents a very diverse panel of African populations that maximizes geographical and ethnic variation and represents a great starting point to achieve the aforementioned goals. However, southern sub-Saharan countries, Bantu speakers and hunter gatherer groups are currently underrepresented, despite being crucial to understand the evolutionary history of the continent. After extensive effort to collate studies documentation, we finally have the opportunity to sequence 600 new individuals from these groups, including countries as Gabon, Rwanda and Zambia, and address these deficiencies. We aim to proceed with the same strategy: to sequence at high depth 25 individuals with standard PCR free libraries, with 2 additional individuals with 10X Genomics Chromium libraries per ethnolinguistic group. The former allows a good representation of variants down to low frequency in any given population, and the latter allows accurate phasing and the analysis of structural variation. By including these new populations, we want to investigate three crucial questions in African history in addition to the initial objectives: the Bantu expansion, the evolutionary history of hunter gatherers and the transatlantic slave trade. Additionally, the expanded dataset will help us better discover the genetic variation present in Africa and characterize the African pangenome.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-18T09:05:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003603","title":"Genetic and expression landscape of Waldenstrom macroglobulinemia","description":"Exome analyses for the identification of somatic mutation in Waldenstrom macroglobulinemia by comparison of tumor and  CD3+(germ line control) population in 16 patients.\ntranscription profiling of a series of Waldenstrom macroglobulinemia samples","abstract":"Exome analyses for the identification of somatic mutation in Waldenstrom macroglobulinemia by comparison of tumor and  CD3+(germ line control) population in 16 patients.\ntranscription profiling of a series of Waldenstrom macroglobulinemia samples","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-18T11:46:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003604","title":"Molecular characterization of adult astroblastoma","description":"xxx","abstract":"xxx","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003605","title":"A Phase II Trial of High Dose Interleukin-2 and Multi-site Stereotactic Ablative Radiotherapy for Patients with Metastatic Renal Cell Carcinoma","description":"Immune-based therapies have improved outcomes for metastatic renal cell carcinoma (mRCC) but there is still a significant margin for improvement. Here, we report the results of a phase II trial combining high dose Interleukin-2 (HD-IL-2) with stereotactic ablative body radiotherapy (SAbR) for patients with metastatic renal cell carcinoma.","abstract":"Immune-based therapies have improved outcomes for metastatic renal cell carcinoma (mRCC) but there is still a significant margin for improvement. Here, we report the results of a phase II trial combining high dose Interleukin-2 (HD-IL-2) with stereotactic ablative body radiotherapy (SAbR) for patients with metastatic renal cell carcinoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-18T23:23:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003606","title":"Cloning expansion of human sperm through nuclear transfer","description":"The ICAHCI embryos were constructed by injecting haploid human embryonic stem cell in to the in vitro matured oocytes followed by activation and culturing in vitro. ICSI embryos were as control generated by injecting single sperm. The embryos was digest with Acctuase and the single cell was collected.","abstract":"The ICAHCI embryos were constructed by injecting haploid human embryonic stem cell in to the in vitro matured oocytes followed by activation and culturing in vitro. ICSI embryos were as control generated by injecting single sperm. The embryos was digest with Acctuase and the single cell was collected.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003607","title":"GWAS Steroid Sensitive Nephrotic Syndrome","description":null,"abstract":"GWAS on a cohort of European ancestry comprising 422 SSNS cases and 5,642 matched controls.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-22T12:35:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003608","title":"GWAS Steroid Sensitive Nephrotic Syndrome","description":null,"abstract":"Background: Steroid-sensitive nephrotic syndrome (SSNS) is the most common form of nephrotic syndrome in childhood. SSNS is considered an autoimmune disease with an established classical human leukocyte antigen (HLA) association; however, the precise etiology of the disease is unclear. In other autoimmune diseases, the identification of loci outside the classical HLA region by genome-wide association studies (GWAS) have provided critical insights into their pathogenesis. Previously conducted GWAS of SSNS have failed to identify non-HLA loci achieving genome-wide significance.\n\nMethods: Here we provide insight into the genetic architecture of SSNS by performing a GWAS on a large cohort of European ancestry comprising 422 cases and 5,642 controls.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003609","title":"Early-onset autoimmunity study","description":null,"abstract":"A young girl from a consanguineous pedigree, presenting with early-onset autoimmunity was sequenced by Whole Exome Sequencing on a Illumina HiSeq2000 sequencer. After demultiplexing and alignment, 97.8 % of reads were uniquely mapped to build 37 of the human reference genome.\nPrior mapping of homozygous intervals by Affymetrix SNPArray based homozygozity mapping results in homozygous stretches that are subject of investigation, to filter for rare variants responsible for autoimmune presentation.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003610","title":"LCM_exomes_Somatic_mutation_in_Primary_Sjogren_s_Syndrome","description":"Whole exome sequencing of LCM derived cell populations from salivary gland biopsies of patients with Primary Sjogren's Syndrome, as well as normal controls","abstract":"Whole exome sequencing of LCM derived cell populations from salivary gland biopsies of patients with Primary Sjogren's Syndrome, as well as normal controls","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003611","title":"Genome-wide cell-free DNA fragmentation in patients with cancer","description":"Cell-free DNA (cfDNA) in the blood provides a noninvasive diagnostic avenue for patients with cancer. However, characteristics of the origins and molecular features of cfDNA are poorly understood.  We developed an approach to evaluate fragmentation patterns of cfDNA across the genome and found that cfDNA profiles of healthy individuals reflected nucleosomal patterns of white blood cells, while patients with cancer had altered fragmentation profiles.  We applied this method to analyze fragmentation profiles of 236 patients with breast, colorectal, lung, ovarian, pancreatic, gastric, or bile duct cancers and 245 healthy individuals.  A machine learning model incorporating genome-wide fragmentation features had sensitivities of detection ranging from 57% to &amp;gt;99% among the seven cancer types at 98% specificity, with an overall AUC of 0.94.  Fragmentation profiles could be used to identify the tissue of origin of the cancers to a limited number of sites in 75% of cases.  Combining our approach with mutation based cfDNA analyses detected 91% of cancer patients.  The results of these analyses highlight important properties of cfDNA and provide a proof of principle approach for screening, early detection, and monitoring of human cancer.","abstract":"Cell-free DNA (cfDNA) in the blood provides a noninvasive diagnostic avenue for patients with cancer. However, characteristics of the origins and molecular features of cfDNA are poorly understood.  We developed an approach to evaluate fragmentation patterns of cfDNA across the genome and found that cfDNA profiles of healthy individuals reflected nucleosomal patterns of white blood cells, while patients with cancer had altered fragmentation profiles.  We applied this method to analyze fragmentation profiles of 236 patients with breast, colorectal, lung, ovarian, pancreatic, gastric, or bile duct cancers and 245 healthy individuals.  A machine learning model incorporating genome-wide fragmentation features had sensitivities of detection ranging from 57% to &amp;gt;99% among the seven cancer types at 98% specificity, with an overall AUC of 0.94.  Fragmentation profiles could be used to identify the tissue of origin of the cancers to a limited number of sites in 75% of cases.  Combining our approach with mutation based cfDNA analyses detected 91% of cancer patients.  The results of these analyses highlight important properties of cfDNA and provide a proof of principle approach for screening, early detection, and monitoring of human cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-24T19:44:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003612","title":"The_British_Autozygosity_Populations_BioResource","description":"This data set contains whole exome sequences of individuals with self-stated parental relatedness from the East London Genes &amp; Health cohort. Rare frequency functional variants in these healthy individuals will be studied with respect to the genetic health of the participants and loss-of-function analysis of human genes.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This data set contains whole exome sequences of individuals with self-stated parental relatedness from the East London Genes &amp; Health cohort. Rare frequency functional variants in these healthy individuals will be studied with respect to the genetic health of the participants and loss-of-function analysis of human genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003613","title":"Genome_wide_MHC_I_CRISPR_Cas9_screening_of_Human_Organoid_Lines","description":"The study will perform genome-wide loss-of-function CRISPR-Cas9 screens to identify tumour cell regulators of immune effector signaling.\n\n*Sequencing is performed on PCR products from the amplification of gRNA segments introduced into commercial cell lines. Cellular DNA or RNA are not sequenced. This data is defined as \"Other Biological/Biochemical Assay Data\" under the WTSI datasharing guidelines and consequently will be released at the time of publication and/or through faculty websites.","abstract":"The goal of this project is to perform genome-wide loss-of-function CRISPR-Cas9 screens to identify tumour cell regulators of immune effector signaling. These results will be used to identify new factors mediating tumour-immune response.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003614","title":"Paired_guide_library_to_identify_synthetically_lethal_genes","description":"Our aim is to identify novel synthetically lethal genes within cancer cells that could potentially be therapeutically targeted in the future. To achieve this, we have designed a paired CRISPR library containing dual guides against genes that are predicted to be synthetically lethal. This library includes sgRNA targeting over 700 gene pairs of interest as well as suitable controls, encompassing in total 25,500 guides. We intent to use this library to screen a panel of cancer cell lines covering multiple tumour types. This should allow us to identify potential synthetically lethal gene pairs both within specific tumour types and those that are more broadly applicable.","abstract":"Our aim is to identify novel synthetically lethal genes within cancer cells that could potentially be therapeutically targeted in the future. To achieve this, we have designed a paired CRISPR library containing dual guides against genes that are predicted to be synthetically lethal. This library includes sgRNA targeting over 700 gene pairs of interest as well as suitable controls, encompassing in total 25,500 guides. We intent to use this library to screen a panel of cancer cell lines covering multiple tumour types. This should allow us to identify potential synthetically lethal gene pairs both within specific tumour types and those that are more broadly applicable.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003615","title":"Targeted DNA sequencing of B-cell lymphoma using LymphoSeq","description":"Tumor-derived genomic DNA from a 589 B-cell lymphomas was sequenced by hybrid capture for 380 genes.  The reads were aligned to the UCSC hg19 assembly bwa and undergone indel alignment, base-level quality recalibration, and PCR duplicate removal using GATK 3.7 and Picard 2.5.0 with Broad’s GATK resource bundle for the hg 19 assembly.","abstract":"Tumor-derived genomic DNA from a 589 B-cell lymphomas was sequenced by hybrid capture for 380 genes.  The reads were aligned to the UCSC hg19 assembly bwa and undergone indel alignment, base-level quality recalibration, and PCR duplicate removal using GATK 3.7 and Picard 2.5.0 with Broad’s GATK resource bundle for the hg 19 assembly.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003616","title":"Kidney_tumour_DNA_exome","description":"This is an exome DNA sequencing study of human renal tumours","abstract":"This is supplementary bulk to single cell RNA sequencing that we are performing","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-26T09:31:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003617","title":"Discovery and capture of novel dynamic DNA methylation in human sperm with preferential links to altered folate metabolism","description":"The sperm DNA methylation landscape is unique and critical for offspring health. If gamete-derived DNA methylation escapes reprogramming in early embryos, epigenetic defects in sperm may be transmitted to the next generation. Current techniques to assess sperm DNA methylation show bias towards CpG dense regions and do not target areas of dynamic methylation, those predicted to be environmentally sensitive and tunable regulatory elements. Thus, this study aim to assess variation in human sperm DNA methylation and design a targeted capture panel to interrogate the human sperm methylome.","abstract":"The sperm DNA methylation landscape is unique and critical for offspring health. If gamete-derived DNA methylation escapes reprogramming in early embryos, epigenetic defects in sperm may be transmitted to the next generation. Current techniques to assess sperm DNA methylation show bias towards CpG dense regions and do not target areas of dynamic methylation, those predicted to be environmentally sensitive and tunable regulatory elements. Thus, this study aim to assess variation in human sperm DNA methylation and design a targeted capture panel to interrogate the human sperm methylome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-26T13:52:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003618","title":"Early-onset autoimmune hemolytic anemia study","description":null,"abstract":"DNA isolated from blood samples from a young boy from a consanguineous pedigree presenting with early-onset autoimmune hemolytic anemia and his mother were sequenced by Whole Exome Sequencing on a Illumina HiSeq2000 sequencer.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003619","title":"FAM50_Chip","description":"This is a Chip-seq experiment using a cancer cell line. Using an antibody we have pulled down DNA that binds to FAM50. FAM50 is a novel protein likely to be a transcription factor.","abstract":"This is a Chip-seq experiment using a cancer cell line. Using an antibody we have pulled down DNA that binds to FAM50. FAM50 is a novel protein likely to be a transcription factor.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003620","title":"Recapitulation of genetic predisposition to medulloblastoma in human neuroepithelial stem cells","description":"Human neural stem cell cultures provide progenitor cells that are potential cells of origin for brain cancers. However, the extent to which genetic predisposition to tumor formation can be faithfully captured in stem cell lines is uncertain. Here we evaluated neuroepithelial stem (NES) cells, representative of cerebellar progenitors. We transduced NES cells with MYCN, observing medulloblastoma upon orthotopic implantation in mice. Significantly, transcriptomes and patterns of DNA methylation from xenograft tumors were globally more representative of human medulloblastoma compared to a MYCN-driven genetically engineered mouse model. Orthotopic transplantation of NES cells generated from Gorlin syndrome, patients predisposed to medulloblastoma due to germline mutated PTCH1, also generated medulloblastoma. We engineered candidate cooperating mutations in Gorlin NES cells, with mutation of DDX3X or loss of GSE1 both accelerating tumorigenesis. These findings demonstrate that human NES cells provide a potent experimental resource for dissecting genetic causation in medulloblastoma.","abstract":"Human neural stem cell cultures provide progenitor cells that are potential cells of origin for brain cancers. However, the extent to which genetic predisposition to tumor formation can be faithfully captured in stem cell lines is uncertain. Here we evaluated neuroepithelial stem (NES) cells, representative of cerebellar progenitors. We transduced NES cells with MYCN, observing medulloblastoma upon orthotopic implantation in mice. Significantly, transcriptomes and patterns of DNA methylation from xenograft tumors were globally more representative of human medulloblastoma compared to a MYCN-driven genetically engineered mouse model. Orthotopic transplantation of NES cells generated from Gorlin syndrome, patients predisposed to medulloblastoma due to germline mutated PTCH1, also generated medulloblastoma. We engineered candidate cooperating mutations in Gorlin NES cells, with mutation of DDX3X or loss of GSE1 both accelerating tumorigenesis. These findings demonstrate that human NES cells provide a potent experimental resource for dissecting genetic causation in medulloblastoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-26T19:42:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003621","title":"Recapitulation of genetic predisposition to medulloblastoma in human neuroepithelial stem cells","description":"Human neural stem cell cultures provide progenitor cells that are potential cells of origin for brain cancers. However, the extent to which genetic predisposition to tumor formation can be faithfully captured in stem cell lines is uncertain. Here we evaluated neuroepithelial stem (NES) cells, representative of cerebellar progenitors. We transduced NES cells with MYCN, observing medulloblastoma upon orthotopic implantation in mice. Significantly, transcriptomes and patterns of DNA methylation from xenograft tumors were globally more representative of human medulloblastoma compared to a MYCN-driven genetically engineered mouse model. Orthotopic transplantation of NES cells generated from Gorlin syndrome, patients predisposed to medulloblastoma due to germline mutated PTCH1, also generated medulloblastoma. We engineered candidate cooperating mutations in Gorlin NES cells, with mutation of DDX3X or loss of GSE1 both accelerating tumorigenesis. These findings demonstrate that human NES cells provide a potent experimental resource for dissecting genetic causation in medulloblastoma.","abstract":"Human neural stem cell cultures provide progenitor cells that are potential cells of origin for brain cancers. However, the extent to which genetic predisposition to tumor formation can be faithfully captured in stem cell lines is uncertain. Here we evaluated neuroepithelial stem (NES) cells, representative of cerebellar progenitors. We transduced NES cells with MYCN, observing medulloblastoma upon orthotopic implantation in mice. Significantly, transcriptomes and patterns of DNA methylation from xenograft tumors were globally more representative of human medulloblastoma compared to a MYCN-driven genetically engineered mouse model. Orthotopic transplantation of NES cells generated from Gorlin syndrome, patients predisposed to medulloblastoma due to germline mutated PTCH1, also generated medulloblastoma. We engineered candidate cooperating mutations in Gorlin NES cells, with mutation of DDX3X or loss of GSE1 both accelerating tumorigenesis. These findings demonstrate that human NES cells provide a potent experimental resource for dissecting genetic causation in medulloblastoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003622","title":"Circadian Clock Properties of T2D Patients","description":null,"abstract":"The circadian system plays an essential role in regulating timing of body metabolism in humans. Indeed, circadian misalignments are strongly associated with high rates of metabolic disorders. Molecular makeup of the circadian oscillator can be deciphered in cells cultured in vitro, and these cellular rhythms are highly informative of the physiological circadian rhythm in vivo.\n\nWe aimed at assessing molecular clock properties in dermal fibroblasts established from the skin biopsies of seventeen Type 2 diabetic obese and non-obese patients and eleven healthy controls. Following in vitro synchronization, primary fibroblast cultures were subjected to continuous assessment of circadian bioluminescence profiles based on lentiviral luciferase reporters. \n\nWe observed a strong inverse correlation between HbA1c values and circadian period length within cells from the Type 2 diabetic group. RNA sequencing analysis conducted in this group samples revealed that ICAM1 encoding for the endothelial adhesion protein was differentially expressed between Type 2 diabetic compensated and non-compensated fibroblasts, and correlated with the period length. Furthermore, ICAM1 expression is driven by rhythmic CLOCK binding. \n\nWe provide for the first time a potential molecular link between severity of Type 2 diabetes and circadian clock machinery, which paves a way for further mechanistic understanding of circadian oscillator changes upon Type 2 diabetes in humans.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-29T09:21:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003623","title":"Novel PARN mutations in Hoyeraal-HReidarsson syndrome patients.","description":"The deposited data correspond to the sequences of PARN gene obtained by whole exome sequencing in two patients carrying mutations in this gene as described in Benyelles et al. EMBO Mol Med 2019.. \nPARN is a poly(A)-specific ribonuclease that regulates the turnover of mRNAs and the maturation and stabilization of the hTR RNA component of telomerase. Data represent Sequences with PARN mutations that have been identified in two patients with Høyeraal-Hreidarsson (HH) syndrome, a rare telomere biology disorder.","abstract":"The deposited data correspond to the sequences of PARN gene obtained by whole exome sequencing in two patients carrying mutations in this gene as described in Benyelles et al. EMBO Mol Med 2019.. \nPARN is a poly(A)-specific ribonuclease that regulates the turnover of mRNAs and the maturation and stabilization of the hTR RNA component of telomerase. Data represent Sequences with PARN mutations that have been identified in two patients with Høyeraal-Hreidarsson (HH) syndrome, a rare telomere biology disorder.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-29T11:29:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003624","title":"WGS of Roma (Romani/Rroma) and European/Romanian individuals from Romania","description":null,"abstract":"The Roma people are the largest transnational ethnic minority in Europe and can be considered the last human migration of South Asian origin into the continent. They departed Northwest India approximately 1,000 years ago, reaching the Balkan Peninsula around the 12th century and Romania in the 14th century. Here, we generated whole-genome sequencing data of Roma (Romani/Rroma) and non-Roma (European/Romanian) individuals from Romania. We performed a genome-wide scan of selection comparing the Roma, their local host population (Romanians), and a Northwestern Indian population to identify the selective pressures faced by the Roma when they settled in Europe.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-29T12:24:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003625","title":"HSC_population_dynamics__scRNA_seq___KX004","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003626","title":"Mutations conferring differential treatment response in breast cancer","description":"Poor prognosis primary breast cancer patients usually receive cytotoxic chemotherapy as a component of treatment, but despite this aggressive therapy recurrences remain common. Improved understanding of chemoresistance pathways would allow better stratification of chemotherapy using predictive markers, and may allow therapeutic inhibition of resistance mechanisms in order to chemosensitise tumours. We aimed to identify molecular pathways that define chemoresponse using the novel approach of examining the selection exerted by neoadjuvant chemotherapy on sub-clonal somatic mutational profiles of cancer cells.","abstract":"Poor prognosis primary breast cancer patients usually receive cytotoxic chemotherapy as a component of treatment, but despite this aggressive therapy recurrences remain common. Improved understanding of chemoresistance pathways would allow better stratification of chemotherapy using predictive markers, and may allow therapeutic inhibition of resistance mechanisms in order to chemosensitise tumours. We aimed to identify molecular pathways that define chemoresponse using the novel approach of examining the selection exerted by neoadjuvant chemotherapy on sub-clonal somatic mutational profiles of cancer cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-29T15:50:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003627","title":"Synthetic modeling reveals HOXB genes are critical for the initiation and maintenance of human leukemia","description":null,"abstract":"We report here an efficient, reproducible model of T-cell leukemia in which lentiviral transduction of normal human cord blood yields aggressive leukemia that appears indistinguishable from natural disease. We utilize this synthetic model to uncover a role for oncogene-induced HOXB activation which is operative in leukemia cells-of-origin and persists in established tumors where it defines a novel subset of patients distinct from other known genetic subtypes and with poor clinical outcome. We show further that anterior HOXB genes are specifically activated in human T-ALL by an epigenetic mechanism and confer growth advantage in both pre-leukemia cells and established clones.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-30T02:51:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003628","title":"Oral mucosa organoids as a potential model for personalized therapies","description":"Organoids were established from both tumor and matched wildtype tissue from patients diagnosed with head and neck squamous cell carcinoma (HNSCC). In order to confirm tumor status and identify oncogenic driver mutations, DNA derived of these organoids was sequenced. After validation of tumor identity, organoids were exposed to a range of (targeted) chemotherapeutics and radiotherapy. Differential responses to therapeutics were subsequently correlated to underlying genetic alterations to see if DNA mutation status could be predictive for responses to therapy.","abstract":"Organoids were established from both tumor and matched wildtype tissue from patients diagnosed with head and neck squamous cell carcinoma (HNSCC). In order to confirm tumor status and identify oncogenic driver mutations, DNA derived of these organoids was sequenced. After validation of tumor identity, organoids were exposed to a range of (targeted) chemotherapeutics and radiotherapy. Differential responses to therapeutics were subsequently correlated to underlying genetic alterations to see if DNA mutation status could be predictive for responses to therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-30T11:38:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003629","title":"UAMS Smoldering Myeloma Myeloma Sequencing","description":"Identifying high risk smoldering myeloma patients and progression mechanism is a prerequisite to implement effective inception strategies and curve myeloma related morbidity and mortality. We hypothesize that genomics may help identify determinants of progression that may help predict outcome and offer effective chemo preventive targets.\nEighty-two patients underwent a custom targeted panel sequencing with an additional capture for the translocation loci. These results were compared to 223 newly diagnosed patients (EGAS00001003223 and EGAD00001004117) and 17 MGUS and 10 early myeloma patients. DNA was obtained from either CD138+ cells from the bone marrow of multiple myeloma patients (tumor) or from stem cell harvests or peripheral blood cells from the same patient (control). 100 ng of DNA was fragmented, end-repaired, and adapters ligated using the HyperPlus kit (KAPA Biosystems). After PCR amplification the libraries were hybridized with probes against either a targeted panel consisting of 140 genes and chromosomal regions (Nimblegen) using SeqCap reagents (Nimblegen). Hybridized libraries underwent further amplification before being sequenced on a NextSeq500 (Illumina) using 75 bp paired end reads.\nOverall, these data highlight the importance of dysregulation of the MAPK pathway in the progression to MM.","abstract":"Identifying high risk smoldering myeloma patients and progression mechanism is a prerequisite to implement effective inception strategies and curve myeloma related morbidity and mortality. We hypothesize that genomics may help identify determinants of progression that may help predict outcome and offer effective chemo preventive targets.\nEighty-two patients underwent a custom targeted panel sequencing with an additional capture for the translocation loci. These results were compared to 223 newly diagnosed patients (EGAS00001003223 and EGAD00001004117) and 17 MGUS and 10 early myeloma patients. DNA was obtained from either CD138+ cells from the bone marrow of multiple myeloma patients (tumor) or from stem cell harvests or peripheral blood cells from the same patient (control). 100 ng of DNA was fragmented, end-repaired, and adapters ligated using the HyperPlus kit (KAPA Biosystems). After PCR amplification the libraries were hybridized with probes against either a targeted panel consisting of 140 genes and chromosomal regions (Nimblegen) using SeqCap reagents (Nimblegen). Hybridized libraries underwent further amplification before being sequenced on a NextSeq500 (Illumina) using 75 bp paired end reads.\nOverall, these data highlight the importance of dysregulation of the MAPK pathway in the progression to MM.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-30T15:44:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003630","title":"CRC GWAS on the Spanish population","description":null,"abstract":"Genome-wide association study performed on the EPICOLON2 cohort, comprising colorectal cancer cases and matched controls of Spanish origin.","study_type":"Cancer Genomics","pubmed_ids":[22310351,23161572,23350875,24218287,30710075],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003631","title":"Breast Cancer - immune clusters - RNA-seq","description":"In this study we use expression data from breast cancer tumors to define immune clusters in breast cancer.\nImmune clusters have gradual levels of immune infiltration. In the intermediate immune infiltration cluster, we found a worse prognosis which is independent of known clinicopathological features. We also found the immune clusters associated with treatment response. Further using gene expression data and deconvolution algorithms to dissect the immune contexture of the clusters.","abstract":"In this study we use expression data from breast cancer tumors to define immune clusters in breast cancer.\nImmune clusters have gradual levels of immune infiltration. In the intermediate immune infiltration cluster, we found a worse prognosis which is independent of known clinicopathological features. We also found the immune clusters associated with treatment response. Further using gene expression data and deconvolution algorithms to dissect the immune contexture of the clusters.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-04-30T18:10:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003632","title":"Breast Cancer - immune clusters - RNA-seq","description":null,"abstract":"In this study we use expression data from breast cancer tumors to define immune clusters in breast cancer.\nImmune clusters have gradual levels of immune infiltration. In the intermediate immune infiltration cluster, we found a worse prognosis which is independent of known clinicopathological features.\nWe also found the immune clusters associated with treatment response.\nFurther using gene expression data and deconvolution algorithms to dissect the immune contexture of the clusters.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003633","title":"CRC GWAS on the Spanish population","description":"Genome-wide association study performed on the EPICOLON2 cohort, comprising colorectal cancer cases and matched controls of Spanish origin.","abstract":"Genome-wide association study performed on the EPICOLON2 cohort, comprising colorectal cancer cases and matched controls of Spanish origin.","study_type":"Other","pubmed_ids":[20710075,22310351,23161572,23350875,24218287],"external_links":null,"is_released":true,"released_date":"2019-05-02T14:20:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003634","title":"Non-invasive prenatal diagnosis by genome-wide haplotyping of maternal cell-free plasma DNA","description":"Whereas non-invasive prenatal testing for aneuploidies (NIPT-A) is widely implemented, non-invasive prenatal testing for monogenic diseases (NIPT-M) is lagging.  By capturing and targeted sequencing of 250000 polymorphic SNP loci from maternal plasma circulating cell-free DNA (cfDNA) and DNA from relatives, the fetal haplotype and chromosomal copy numbers are deduced. In all families tested, the cfDNA derived haplotypes are on average 97% concordant with the neonatal and embryo haplotype. This generic non-invasive prenatal diagnostic approach allows cost efficient scrutinizing the fetal genome for the presence of any inherited monogenic disease or trait.","abstract":"Whereas non-invasive prenatal testing for aneuploidies (NIPT-A) is widely implemented, non-invasive prenatal testing for monogenic diseases (NIPT-M) is lagging.  By capturing and targeted sequencing of 250000 polymorphic SNP loci from maternal plasma circulating cell-free DNA (cfDNA) and DNA from relatives, the fetal haplotype and chromosomal copy numbers are deduced. In all families tested, the cfDNA derived haplotypes are on average 97% concordant with the neonatal and embryo haplotype. This generic non-invasive prenatal diagnostic approach allows cost efficient scrutinizing the fetal genome for the presence of any inherited monogenic disease or trait.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-02T14:53:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003635","title":"Genome‐wide postnatal changes in immunity following fetal inflammatory response","description":"The fetal inflammatory response (FIR) increases the risk of perinatal brain injury, particularly in extremely low gestational age newborns (ELGANs, &lt; 28 weeks of gestation). One of the mechanisms contributing to such a risk is a postnatal intermittent or sustained systemic inflammation (ISSI) following FIR. The link between prenatal and postnatal systemic inflammation is supported by the presence of well‐established inflammatory biomarkers in the umbilical cord and peripheral blood. However, the extent of molecular changes contributing to this association is unknown. Using RNA sequencing and mass spectrometry proteomics, we profiled the transcriptome and proteome of archived neonatal dried blood spot (DBS) specimens from 21 ELGANs. Comparing FIR‐affected and unaffected ELGANs, we identified 782 gene and 27 protein expression changes of 50% magnitude or more, and an experiment‐wide significance level below 5% false discovery rate. These expression changes confirm the robust postnatal activation of the innate immune system in FIR‐affected ELGANs and reveal for the first time an impairment of their adaptive immunity. In turn, the altered pathways provide clues about the molecular mechanisms triggering ISSI after FIR, and the onset of perinatal brain injury.","abstract":"The fetal inflammatory response (FIR) increases the risk of perinatal brain injury, particularly in extremely low gestational age newborns (ELGANs, &lt; 28 weeks of gestation). One of the mechanisms contributing to such a risk is a postnatal intermittent or sustained systemic inflammation (ISSI) following FIR. The link between prenatal and postnatal systemic inflammation is supported by the presence of well‐established inflammatory biomarkers in the umbilical cord and peripheral blood. However, the extent of molecular changes contributing to this association is unknown. Using RNA sequencing and mass spectrometry proteomics, we profiled the transcriptome and proteome of archived neonatal dried blood spot (DBS) specimens from 21 ELGANs. Comparing FIR‐affected and unaffected ELGANs, we identified 782 gene and 27 protein expression changes of 50% magnitude or more, and an experiment‐wide significance level below 5% false discovery rate. These expression changes confirm the robust postnatal activation of the innate immune system in FIR‐affected ELGANs and reveal for the first time an impairment of their adaptive immunity. In turn, the altered pathways provide clues about the molecular mechanisms triggering ISSI after FIR, and the onset of perinatal brain injury.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-02T15:27:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003636","title":"HSC_population_dynamics___TQ104_sample","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003637","title":"MutWP6__CRUK_Grand_Challenge_Mutographs_of_Cancer__alkylating_agents","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nWithin Mutographs, work lead by the Sanger Institute will investigate whether detection of somatic mutations and mutational signatures in circulating white blood cells can be developed into a practical, generic system for surveying and monitoring multiple different endogenous and exogenous exposures, providing an ‘observatory’ on somatic mutational processes in humans.\n\nWhole genome sequences are generated at the Wellcome Sanger Institute (Illumina HiSeqX). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nWithin Mutographs, work lead by the Sanger Institute will investigate whether detection of somatic mutations and mutational signatures in circulating white blood cells can be developed into a practical, generic system for surveying and monitoring multiple different endogenous and exogenous exposures, providing an ‘observatory’ on somatic mutational processes in humans.\n\nWhole genome sequences are generated at the Wellcome Sanger Institute (Illumina HiSeqX). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-03T17:17:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003638","title":"Effect of 28-day administration of Urolithin A to sedentary elderly on muscle gene expression","description":"Urolithin A (UA) is a natural dietary, microflora derived, metabolite shown to stimulate mitophagy and improve muscle health in old animals and pre-clinical models of aging. UA was administered for 28-day in a first-in-human clinical trial to sedentary elderly subjects. Muscle biopsies were collected before the first dosing, and at the end of the 28-day period, under fasted conditions. Gene expression was measured by microarray. Gene-set enrichment analysis of the gene expression data showed that UA increased the transcription of mitochondrial related genesets. These observed effects on mitochondrial biomarkers show that UA induces a molecular signature of improved mitochondrial and cellular health following regular oral consumption in humans.","abstract":"Urolithin A (UA) is a natural dietary, microflora derived, metabolite shown to stimulate mitophagy and improve muscle health in old animals and pre-clinical models of aging. UA was administered for 28-day in a first-in-human clinical trial to sedentary elderly subjects. Muscle biopsies were collected before the first dosing, and at the end of the 28-day period, under fasted conditions. Gene expression was measured by microarray. Gene-set enrichment analysis of the gene expression data showed that UA increased the transcription of mitochondrial related genesets. These observed effects on mitochondrial biomarkers show that UA induces a molecular signature of improved mitochondrial and cellular health following regular oral consumption in humans.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-03T15:21:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003639","title":"Genome-wide search to find the genetic elements underlying visual contour perception","description":"Contour integration is a key function of the visual system to deal with occlusion and discontinuity in natural scenes. The current study is the first one to investigate the genetic basis of this visual function in humans. A total of 2619 normal participants were tested on their ability to detect continuous contours embedded in a cluttered background with a standard psychophysical protocol. Multi-level genomic analysis was performed, involving heritability estimation based on single nucleotide polymorphism (SNP) and association testing at SNP and gene levels.","abstract":"Contour integration is a key function of the visual system to deal with occlusion and discontinuity in natural scenes. The current study is the first one to investigate the genetic basis of this visual function in humans. A total of 2619 normal participants were tested on their ability to detect continuous contours embedded in a cluttered background with a standard psychophysical protocol. Multi-level genomic analysis was performed, involving heritability estimation based on single nucleotide polymorphism (SNP) and association testing at SNP and gene levels.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-04T12:25:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003640","title":"RNA-seq of breast cancer samples with breast MRI available from the MARGINS project.","description":"Breast cancer is characterized by high heterogeneity in its phenotype on magnetic resonance imaging (MRI). Better understanding of the molecular biology associated with the different phenotypes on dynamic contrast-enhanced MRI (DCE-MRI) may ultimately aid in the diagnosis and prognosis of breast cancer. In this study we aimed to discover the molecular biology in breast cancers as measured by gene expression profiling that underlies the phenotypes seen on MRI. Therefore,we retrospectively collected tumor RNA for sequencing from breast cancer patients imaged in the MARGINS study between 2000 and 2008.","abstract":"Breast cancer is characterized by high heterogeneity in its phenotype on magnetic resonance imaging (MRI). Better understanding of the molecular biology associated with the different phenotypes on dynamic contrast-enhanced MRI (DCE-MRI) may ultimately aid in the diagnosis and prognosis of breast cancer. In this study we aimed to discover the molecular biology in breast cancers as measured by gene expression profiling that underlies the phenotypes seen on MRI. Therefore,we retrospectively collected tumor RNA for sequencing from breast cancer patients imaged in the MARGINS study between 2000 and 2008.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003641","title":"RNA-seq as a tool for evaluating human embryo competence","description":"The majority of embryos that are created through IVF do not implant. One possibility for this inefficiency is an incomplete understanding of the molecular factors affecting embryo competence. Currently, the process of selecting an embryo for uterine transfer utilizes an ad-hoc combination of morphological criteria, the kinetics of development, and genetic testing for aneuploidy. However, no single criterion can ensure selection of a viable embryo. In contrast, RNA-sequencing of embryos could yield highly dimensional data, which may provide additional insight and illuminate the discrepancies among current selection criteria. Indeed, recent advances enabling the production of RNA-sequencing (RNA-seq) libraries from single cells have facilitated the application of this technique to the study of some transcriptional events in early human development. However, these studies have not assessed the quality of their constituent embryos relative to commonly used embryological criteria. Here, we perform proof-of-principle advancement to clinical selection procedures by generating high quality RNA-seq libraries from a trophectoderm biopsy as well as the remaining whole embryo. We combine state-of-the-art embryological methods with low-input RNA-seq to develop the first transcriptome-wide approach for use in future predictive embryology studies. Specifically, we demonstrate the capacity of RNA-seq as a promising tool in preimplantation screening by showing that biopsies of an embryo can capture valuable information content available in the whole embryo from which they are derived. Furthermore, we show that this technique can be used to generate a RNA-based digital karyotype, and to develop a foundational dataset for identifying candidate competence-associated genes. Together, these data establish the foundation for a future RNA-based diagnostic in IVF.","abstract":"The majority of embryos that are created through IVF do not implant. One possibility for this inefficiency is an incomplete understanding of the molecular factors affecting embryo competence. Currently, the process of selecting an embryo for uterine transfer utilizes an ad-hoc combination of morphological criteria, the kinetics of development, and genetic testing for aneuploidy. However, no single criterion can ensure selection of a viable embryo. In contrast, RNA-sequencing of embryos could yield highly dimensional data, which may provide additional insight and illuminate the discrepancies among current selection criteria. Indeed, recent advances enabling the production of RNA-sequencing (RNA-seq) libraries from single cells have facilitated the application of this technique to the study of some transcriptional events in early human development. However, these studies have not assessed the quality of their constituent embryos relative to commonly used embryological criteria. Here, we perform proof-of-principle advancement to clinical selection procedures by generating high quality RNA-seq libraries from a trophectoderm biopsy as well as the remaining whole embryo. We combine state-of-the-art embryological methods with low-input RNA-seq to develop the first transcriptome-wide approach for use in future predictive embryology studies. Specifically, we demonstrate the capacity of RNA-seq as a promising tool in preimplantation screening by showing that biopsies of an embryo can capture valuable information content available in the whole embryo from which they are derived. Furthermore, we show that this technique can be used to generate a RNA-based digital karyotype, and to develop a foundational dataset for identifying candidate competence-associated genes. Together, these data establish the foundation for a future RNA-based diagnostic in IVF.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003642","title":"Pangenomic classification of pituitary adenomas","description":"Pituitary neuroendocrine tumors (PitNETs) are common. They are classified in five main histological types: PitNETs of POU1F1 (Pit1) lineage -lactotroph, somatotroph and thyrotroph -, gonadotroph, and corticotroph PitNETs. Pituitary tumorigenesis is poorly understood.  We report here a pangenomic characterization of 134 PitNETs from all types, based on exome, genome, transcriptome, miRnome and methylome. Pit1 lineage was associated with a specific epigenetic signature of diffuse DNA hypomethylation, and correlated with expression of Pit1 markers and chromosomal instability. 45% of somatotroph PitNETs showed GNAS mutations. GNAS-wild type somatotroph showed a distinct transcriptome profile, expressing gonadotroph transcription factor NR5A1 (SF1). Sparsely granulated somatotroph PitNETs was classified apart from somatotroph, owing to a thyrotroph transcriptome signature. 43% of corticotroph PitNETs showed USP8 mutations, sharing a low epithelial-mesenchimal transition (EMT) transcriptome signature. Silent corticotroph PitNETs showed a gonadotroph transcriptome signature evoking transdifferentiation, and lost somatostatin target SSTR5 expression.","abstract":"Pituitary neuroendocrine tumors (PitNETs) are common. They are classified in five main histological types: PitNETs of POU1F1 (Pit1) lineage -lactotroph, somatotroph and thyrotroph -, gonadotroph, and corticotroph PitNETs. Pituitary tumorigenesis is poorly understood.  We report here a pangenomic characterization of 134 PitNETs from all types, based on exome, genome, transcriptome, miRnome and methylome. Pit1 lineage was associated with a specific epigenetic signature of diffuse DNA hypomethylation, and correlated with expression of Pit1 markers and chromosomal instability. 45% of somatotroph PitNETs showed GNAS mutations. GNAS-wild type somatotroph showed a distinct transcriptome profile, expressing gonadotroph transcription factor NR5A1 (SF1). Sparsely granulated somatotroph PitNETs was classified apart from somatotroph, owing to a thyrotroph transcriptome signature. 43% of corticotroph PitNETs showed USP8 mutations, sharing a low epithelial-mesenchimal transition (EMT) transcriptome signature. Silent corticotroph PitNETs showed a gonadotroph transcriptome signature evoking transdifferentiation, and lost somatostatin target SSTR5 expression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-07T10:40:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003643","title":"Presence of bacterial infection in brains of patients with Parkinson's disease (PD)","description":"Isolation of bacteria in infected brains in patients with Parkinson's disease. Here we used next generation sequencing of 16S ribosomal RNA gene PCR amplicons (NGS 16S amplicon analysis).","abstract":"Isolation of bacteria in infected brains in patients with Parkinson's disease. Here we used next generation sequencing of 16S ribosomal RNA gene PCR amplicons (NGS 16S amplicon analysis).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-07T10:57:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003644","title":"Presence of fungal infection in brains of patients with Parkinsons disease (PD)","description":"Isolation of fungi in infected neural tissues in patients with Parkinson's disease. Here we used next generation sequencing of Internal Transcribed Spacer (ITS) regions, by PCR amplicons (NGS ITS amplicon analysis).","abstract":"Isolation of fungi in infected neural tissues in patients with Parkinson's disease. Here we used next generation sequencing of Internal Transcribed Spacer (ITS) regions, by PCR amplicons (NGS ITS amplicon analysis).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-07T13:01:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003645","title":"GWAS Results from Danjou et al, Nature Genetics 2015","description":"We report genome-wide association study results for the levels of A1, A2 and fetal hemoglobins, analyzed for the first time concurrently. Integrating high-density array genotyping and whole-genome sequencing in a large general population cohort from Sardinia, we detected 23 associations at 10 loci. Five signals are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, ZFPM1 (FOG1), NFIX and CCND3. Among the signals at known loci, ten are new lead variants and four are new independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and identified features of coordinated hemoglobin species production.","abstract":"We report genome-wide association study results for the levels of A1, A2 and fetal hemoglobins, analyzed for the first time concurrently. Integrating high-density array genotyping and whole-genome sequencing in a large general population cohort from Sardinia, we detected 23 associations at 10 loci. Five signals are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, ZFPM1 (FOG1), NFIX and CCND3. Among the signals at known loci, ten are new lead variants and four are new independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and identified features of coordinated hemoglobin species production.","study_type":"Other","pubmed_ids":[26366553],"external_links":null,"is_released":true,"released_date":"2019-05-07T15:10:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003646","title":"Latency and interval therapy affect the evolution in metastatic colorectal cancer","description":"While comparison of primary tumor and metastases has highlighted genomic heterogeneity in colorectal cancer (CRC), previous studies have focused on a single metastatic site or limited genomic testing. Combining data from whole exome and ultra-deep targeted sequencing, we explored possible evolutionary trajectories beyond the status of these mutations, particularly among patient-matched metastatic tumors. Our findings confirm the persistence of known clinically-relevant mutations (e.g. those of RAS family of oncogenes) in CRC primary and metastases, yet reveal that latency and interval systemic therapy affect the course of evolutionary events within metastatic lesions. Specifically, our analysis of patient-matched primary and multiple metastatic lesions, developed over time, showed a similar genetic composition for liver metastatic tumors, which were 21-months apart. This genetic makeup was different from those identified in lung metastases developed before manifestation of the second liver metastasis. These results underscore the role of dormancy in the evolutionary path of metastatic CRC.","abstract":"While comparison of primary tumor and metastases has highlighted genomic heterogeneity in colorectal cancer (CRC), previous studies have focused on a single metastatic site or limited genomic testing. Combining data from whole exome and ultra-deep targeted sequencing, we explored possible evolutionary trajectories beyond the status of these mutations, particularly among patient-matched metastatic tumors. Our findings confirm the persistence of known clinically-relevant mutations (e.g. those of RAS family of oncogenes) in CRC primary and metastases, yet reveal that latency and interval systemic therapy affect the course of evolutionary events within metastatic lesions. Specifically, our analysis of patient-matched primary and multiple metastatic lesions, developed over time, showed a similar genetic composition for liver metastatic tumors, which were 21-months apart. This genetic makeup was different from those identified in lung metastases developed before manifestation of the second liver metastasis. These results underscore the role of dormancy in the evolutionary path of metastatic CRC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-07T16:47:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003647","title":"Mapping genetic variants that underlie gene regulation in intestinal cell types to identify novel, validated, Crohn’s disease drug targets","description":"Biopsies from the terminal ileum and rectum of healthy individuals and terminal ileum and blood from Crohns disease patients are collected and  processed single cells and processed for single-cell RNA-sequencing using 10X Genomics 3' v3 and v3.1 and Illumina sequencing.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Biopsies from the terminal ileum and rectum of healthy individuals and terminal ileum and blood from Crohns disease patients are collected and  processed single cells and processed for single-cell RNA-sequencing using 10X Genomics 3' v3 and v3.1 and Illumina sequencing.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-08T13:40:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003648","title":"Whole genome sequencing of six ethnic groups from Burkina Faso, Cameroon, and Tanzania","description":"We conducted low-coverage (~10x) sequencing of six ethnic groups from three malaria-endemic countries in\nsub-Saharan Africa, with the aim of characterising genetic diversity and improving imputation performance\nfor genotyped samples in these populations.  This data is part of a pre-publication\nrelease and is available under managed access.  Please see https://www.malariagen.net/data/terms-use/human-gwas-data for\nmore information on MalariaGEN data access policies.\n\nThe purpose of the project was to support the discovery and understanding of genetic variants that influence human\ndisease.  Specifically defined goals were:\n\n  a. the discovery of single nucleotide variants at frequencies of 1% or higher in diverse populations,\n  b. even more comprehensive discovery (variants down to frequencies of 0.1 - 0.5%) in functional gene regions, and\n  c. discovery of structural variants, such as copy number variants, other insertions and deletions, and inversions, including sequence-level understanding of breakpoints.","abstract":"We conducted low-coverage (~10x) sequencing of six ethnic groups from three malaria-endemic countries in\nsub-Saharan Africa, with the aim of characterising genetic diversity and improving imputation performance\nfor genotyped samples in these populations.  This data is part of a pre-publication\nrelease and is available under managed access.  Please see https://www.malariagen.net/data/terms-use/human-gwas-data for\nmore information on MalariaGEN data access policies.\n\nThe purpose of the project was to support the discovery and understanding of genetic variants that influence human\ndisease.  Specifically defined goals were:\n\n  a. the discovery of single nucleotide variants at frequencies of 1% or higher in diverse populations,\n  b. even more comprehensive discovery (variants down to frequencies of 0.1 - 0.5%) in functional gene regions, and\n  c. discovery of structural variants, such as copy number variants, other insertions and deletions, and inversions, including sequence-level understanding of breakpoints.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-08T16:53:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003649","title":"Genomic and transcriptomic profiling of combined hepatocellular and intrahepatic cholangiocarcinoma reveals distinct molecular subtypes","description":null,"abstract":"cHCC-ICC is a rare type of liver cancer with dismal prognosis, its accurate diagnosis and specialized treatment are unmet clinical needs. Moreover, whether cHCC-ICC is a unique entity or a subtype of hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) is a long-standing controversy. We portrayed a detailed genomic landscape of cHCC-ICC, performed a comprehensive comparison of cHCC-ICC with HCC and ICC, and provided a rationale for the development of accurate diagnostic approach and specialized treatment for cHCC-ICC patients.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003650","title":"WGBS analysis corresponding to representative cases of iBCP-ALL patients","description":"In this study, we performed whole genome bisulfite sequencing (WGBS) to characterize the methylome of representative iBCP-ALL cases from the Interfant study discovery cohort, including 2 pools of B-cell progenitors from healthy donors, 2 MLL-AF4+, 2 MLL-AF9+ and 2 non-MLLs from iBCP-ALL patients.","abstract":"In this study, we performed whole genome bisulfite sequencing (WGBS) to characterize the methylome of representative iBCP-ALL cases from the Interfant study discovery cohort, including 2 pools of B-cell progenitors from healthy donors, 2 MLL-AF4+, 2 MLL-AF9+ and 2 non-MLLs from iBCP-ALL patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-10T14:49:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003651","title":"multi-OMICs study of a pair of infant monozygotic twins with concordant B-cell ALL","description":"B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common cancer in childhood. Studying identical twins with B-cell ALL provides a unique and tractable model for deciphering the developmental timing of pre- and post-natal mutations contributing to clonal evolution. To date, this has mainly focused on major cytogenetic subgroups of childhood B-cell ALL, including MLL fusions, ETV6-RUNX1, hyperdiploidy, and BCR-ABL1. However, formal demonstration of the prenatal origin and “backtracking” the natural history of the leukemia remains understudied in “B-other”/Normal Karyotype (NK) B-cell ALL. To characterize the genetic and the epigenetic landscape of this particular leukemia subtype, we performed whole genome DNA-, B-cell receptor (BCR)-, and DNA bisulfite-sequencing on a pair of 8-month-old monozygotic twins diagnosed with concordant “B-other”/NK B-cell ALL.","abstract":"B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common cancer in childhood. Studying identical twins with B-cell ALL provides a unique and tractable model for deciphering the developmental timing of pre- and post-natal mutations contributing to clonal evolution. To date, this has mainly focused on major cytogenetic subgroups of childhood B-cell ALL, including MLL fusions, ETV6-RUNX1, hyperdiploidy, and BCR-ABL1. However, formal demonstration of the prenatal origin and “backtracking” the natural history of the leukemia remains understudied in “B-other”/Normal Karyotype (NK) B-cell ALL. To characterize the genetic and the epigenetic landscape of this particular leukemia subtype, we performed whole genome DNA-, B-cell receptor (BCR)-, and DNA bisulfite-sequencing on a pair of 8-month-old monozygotic twins diagnosed with concordant “B-other”/NK B-cell ALL.","study_type":"Other","pubmed_ids":[31221673],"external_links":null,"is_released":true,"released_date":"2019-05-12T18:39:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003652","title":"Accelerated clonal evolution in refractory versus relapsed chronic lymphocytic leukemia upon treatment","description":"Identify and track clonal evolution of clones in consecutive human chronic lymphocytic leukemia samples identified by whole exome sequencing.","abstract":"Identify and track clonal evolution of clones in consecutive human chronic lymphocytic leukemia samples identified by whole exome sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-13T15:26:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003653","title":"Indonesian methylation data","description":"DNA methylation data were collected to study patterns of functional variation across the broad geography of Indonesia. The region has extremely diverse populations, with very different demographic histories and multiple genetic ancestries. This dataset reports Illumina Epic methylation chip data for individuals from three islands spanning this geographical region: Mentawai, Sumba and West Papua.","abstract":"DNA methylation data were collected to study patterns of functional variation across the broad geography of Indonesia. The region has extremely diverse populations, with very different demographic histories and multiple genetic ancestries. This dataset reports Illumina Epic methylation chip data for individuals from three islands spanning this geographical region: Mentawai, Sumba and West Papua.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-15T03:30:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003654","title":"Indonesian Genome Diversity Project 2","description":"High-coverage whole genome sequences were collected to study patterns of genomic variation across the broad geography of Indonesia and New Guinea. This region has experienced an extremely complex demographic history, including repeated bouts of admixture with archaic and modern human groups. This dataset reports whole genome sequences for 82 individuals from different populations from Mentawai, New Guinea, Sumatra and Sumba islands. Particular attention has been paid in the original study to genomic signals that are informative for population history, including admixture with archaic hominins and the role of modern human admixture during the late Pleistocene and Holocene.","abstract":"High-coverage whole genome sequences were collected to study patterns of genomic variation across the broad geography of Indonesia and New Guinea. This region has experienced an extremely complex demographic history, including repeated bouts of admixture with archaic and modern human groups. This dataset reports whole genome sequences for 82 individuals from different populations from Mentawai, New Guinea, Sumatra and Sumba islands. Particular attention has been paid in the original study to genomic signals that are informative for population history, including admixture with archaic hominins and the role of modern human admixture during the late Pleistocene and Holocene.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-16T05:20:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003655","title":"The repertoire of serous ovarian cancer phenotypic heterogeneity revealed by single-cell sequencing of normal fallopian tube epithelial cells","description":"Plasticity and non-genetic heterogeneity enable cancer cells to interchange between cell states to accomplish diverse functions. The molecular physiognomy of cell states ensures robust tumour stratification with prognostic and therapeutic implications. We performed single-cell sequencing of more than 3900 normal fallopian tube epithelial (FTE) cells, the presumed cells of origin of high-grade serous ovarian cancer (HGSOC) and identified six molecular FTE subtypes. We show that individual serous ovarian carcinomas can be classified based on their deconvolution into constituent FTE molecular subtypes. We identify a HGSOC subtype that is enriched in markers of the FTE mesenchymal subtype and that is robustly correlated with poor prognosis. Our findings lay the foundation for accurate prognostic and therapeutic stratification of serous ovarian cancer.","abstract":"Plasticity and non-genetic heterogeneity enable cancer cells to interchange between cell states to accomplish diverse functions. The molecular physiognomy of cell states ensures robust tumour stratification with prognostic and therapeutic implications. We performed single-cell sequencing of more than 3900 normal fallopian tube epithelial (FTE) cells, the presumed cells of origin of high-grade serous ovarian cancer (HGSOC) and identified six molecular FTE subtypes. We show that individual serous ovarian carcinomas can be classified based on their deconvolution into constituent FTE molecular subtypes. We identify a HGSOC subtype that is enriched in markers of the FTE mesenchymal subtype and that is robustly correlated with poor prognosis. Our findings lay the foundation for accurate prognostic and therapeutic stratification of serous ovarian cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003656","title":"Healthspan and lifespan extension by fecal microbiota transplantation in progeroid mice","description":"The gut microbiome is emerging as a key regulator of several metabolic, immune and neuroendocrine pathways. Gut microbiome deregulation has been implicated in major conditions such as obesity, type 2 diabetes, cardiovascular disease, non-alcoholic fatty acid liver disease or cancer, but its precise role in aging remains to be elucidated. Here, we characterize the gut microbiome profile of accelerated aging and show that its external modulation is sufficient to extend healthspan and lifespan. We found that two different mouse models of progeria present with intestinal dysbiosis, which is characterized, among other alterations, by an increment in proteobacteria, cyanobacteria and a loss in verrucomicrobia, whereas long-lived humans (i.e., centenarians) exhibit a remarkable increase in verrucomicrobia and a reduction in proteobacteria. Fecal microbiota transplantation proved to be effective to enhance healthspan and lifespan in both progeroid mouse models and, more importantly, the solely transplantation with the verrucomicrobia Akkermansia muciniphila was sufficient to exert beneficial effects. Our results demonstrate that intestinal dysbiosis is a phenotype associated with accelerated aging and its correction provides health benefits. Moreover, metabolomic analysis of ileal content points to the restoration of secondary bile acids as a possible mechanism for the beneficial outcome of reestablishing a healthy microbiome. Our results suggest the existence of a link between gut aging and the microbiota, and can help to gain insight into the rationale for microbiome-based interventions against age-related diseases. Mouse sequence data have been deposited in ENA (https://www.ebi.ac.uk/ena) under accession number PRJEB34214","abstract":"The gut microbiome is emerging as a key regulator of several metabolic, immune and neuroendocrine pathways. Gut microbiome deregulation has been implicated in major conditions such as obesity, type 2 diabetes, cardiovascular disease, non-alcoholic fatty acid liver disease or cancer, but its precise role in aging remains to be elucidated. Here, we characterize the gut microbiome profile of accelerated aging and show that its external modulation is sufficient to extend healthspan and lifespan. We found that two different mouse models of progeria present with intestinal dysbiosis, which is characterized, among other alterations, by an increment in proteobacteria, cyanobacteria and a loss in verrucomicrobia, whereas long-lived humans (i.e., centenarians) exhibit a remarkable increase in verrucomicrobia and a reduction in proteobacteria. Fecal microbiota transplantation proved to be effective to enhance healthspan and lifespan in both progeroid mouse models and, more importantly, the solely transplantation with the verrucomicrobia Akkermansia muciniphila was sufficient to exert beneficial effects. Our results demonstrate that intestinal dysbiosis is a phenotype associated with accelerated aging and its correction provides health benefits. Moreover, metabolomic analysis of ileal content points to the restoration of secondary bile acids as a possible mechanism for the beneficial outcome of reestablishing a healthy microbiome. Our results suggest the existence of a link between gut aging and the microbiota, and can help to gain insight into the rationale for microbiome-based interventions against age-related diseases. Mouse sequence data have been deposited in ENA (https://www.ebi.ac.uk/ena) under accession number PRJEB34214","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-17T11:58:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003657","title":"Human pan-genome analysis","description":"The reference human genome is still incomplete, and several non-reference sequences have derived from diverse populations. With the available of whole genome sequencing data from multiple individuals, we could construct the pan-genome sequence. Here we provide high quality genome sequencing (~30x coverage) from 185 Han Chinese individuals. All samples were sequenced using Illumina HiSeq X10 sequencer and paired-end 150-bp reads were produced.","abstract":"The reference human genome is still incomplete, and several non-reference sequences have derived from diverse populations. With the available of whole genome sequencing data from multiple individuals, we could construct the pan-genome sequence. Here we provide high quality genome sequencing (~30x coverage) from 185 Han Chinese individuals. All samples were sequenced using Illumina HiSeq X10 sequencer and paired-end 150-bp reads were produced.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-18T05:02:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003658","title":"Epitope-linked Ig-seq of self-reactive plasma cells in celiac disease","description":null,"abstract":"Autoantibodies against the enzyme transglutaminase 2 (TG2) are a hallmark of celiac disease, and plasma cells secreting TG2-specific IgA are frequent in the gut mucosa of patients. In order to study targeting of distinct antigenic TG2 regions by antibodies, we isolated single gut plasma cells reactive either with wild-type TG2 only or with both wild-type TG2 and a chimeric TG3/TG2 protein lacking the main antigenic domain. Sequencing of the immunoglobulin variable regions of  803 single cells from five celiac patients revealed somatic mutation patterns and V-segment preferences reflecting the epitope targeted by individual cells.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-20T16:32:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003659","title":"Genomic Signatures Reveal DNA Damage Response Deficiency in Brain Metastases of Colorectal Cancer","description":"Brain metastasis (BM) of colorectal cancer (CRC) is rare but lethal, and lacks effective therapies or a good understanding of its genomic landscapes. We conduct an analysis of whole-exome sequencing (WES) and whole-genome sequencing (WGS) data on 19 trios of patient-matched BMs, primary CRC tumors, and adjacent normal tissue to (1) document genomic signatures during the evolution of CRC BM; (2) identify clinically actionable targets for the BM treatment; and (3) identify potential drivers in CRC BM.","abstract":"Brain metastasis (BM) of colorectal cancer (CRC) is rare but lethal, and lacks effective therapies or a good understanding of its genomic landscapes. We conduct an analysis of whole-exome sequencing (WES) and whole-genome sequencing (WGS) data on 19 trios of patient-matched BMs, primary CRC tumors, and adjacent normal tissue to (1) document genomic signatures during the evolution of CRC BM; (2) identify clinically actionable targets for the BM treatment; and (3) identify potential drivers in CRC BM.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-20T14:55:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003660","title":"Whole-genome and transcriptome sequencing of blastic plasmacytoid dendritic cell neoplasm","description":null,"abstract":"Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive malignancy derived from plasmacytoid dendritic cell precursors. We subjected tumor biopsies from patients with BPDCN to whole-genome sequencing and RNA-sequencing to investigate genomic alterations and deregulated gene expression in the disease.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-20T15:30:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003661","title":"Bioinformatic Methods and Bridging of Assay Results for Reliable Tumor Mutational Burden Assessment in Non-Small Cell Lung Cancer","description":"Tumor mutational burden (TMB) has emerged as a predictive biomarker of response to immune checkpoint inhibitors. Standardization of TMB measurement is essential for implementing diagnostic tools to guide treatment. Here we evaluate bioinformatic TMB analysis by whole exome sequencing (WES) in formalin-fixed, paraffin-embedded samples. In CheckMate 026, TMB was retrospectively assessed in 312 patients with non-small cell lung cancer (58% of the intent-to-treat population) who received first-line nivolumab treatment or chemotherapy. We examined the sensitivity of TMB assessment to bioinformatic filtering methods and assessed concordance between TMB data derived by WES and the FoundationOne CDx™ assay. TMB scores comprising synonymous, indel, frameshift, and nonsense mutations (all mutations) were 3.1-fold higher than data including missense mutations only, but values were highly correlated (Spearman’s r = 0.99). Scores from CheckMate 026 samples including missense mutations only were similar to those generated from data in The Cancer Genome Atlas, but those including all mutations were generally higher. Using databases for germline subtraction (instead of matched controls) showed a trend for race-dependent increases in TMB scores. Parameter variation can therefore impact TMB calculations, highlighting the need for standardization. Encouragingly, WES and FoundationOne CDx outputs were highly correlated (Spearman’s r = 0.90) and differences could be accounted for by empirical calibration, suggesting that reliable TMB assessment across assays, platforms and centers is achievable.","abstract":"Tumor mutational burden (TMB) has emerged as a predictive biomarker of response to immune checkpoint inhibitors. Standardization of TMB measurement is essential for implementing diagnostic tools to guide treatment. Here we evaluate bioinformatic TMB analysis by whole exome sequencing (WES) in formalin-fixed, paraffin-embedded samples. In CheckMate 026, TMB was retrospectively assessed in 312 patients with non-small cell lung cancer (58% of the intent-to-treat population) who received first-line nivolumab treatment or chemotherapy. We examined the sensitivity of TMB assessment to bioinformatic filtering methods and assessed concordance between TMB data derived by WES and the FoundationOne CDx™ assay. TMB scores comprising synonymous, indel, frameshift, and nonsense mutations (all mutations) were 3.1-fold higher than data including missense mutations only, but values were highly correlated (Spearman’s r = 0.99). Scores from CheckMate 026 samples including missense mutations only were similar to those generated from data in The Cancer Genome Atlas, but those including all mutations were generally higher. Using databases for germline subtraction (instead of matched controls) showed a trend for race-dependent increases in TMB scores. Parameter variation can therefore impact TMB calculations, highlighting the need for standardization. Encouragingly, WES and FoundationOne CDx outputs were highly correlated (Spearman’s r = 0.90) and differences could be accounted for by empirical calibration, suggesting that reliable TMB assessment across assays, platforms and centers is achievable.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-21T13:03:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003662","title":"Combined genetic and transcriptome analysis of patients with Systemic Lupus Erythematosus (SLE)","description":"A comprehensive profiling of the genomic architecture of Systemic Lupus Erythematosus (SLE) by combining genetic and transscriptomic analysis by RNA-seq.","abstract":"A comprehensive profiling of the genomic architecture of Systemic Lupus Erythematosus (SLE) by combining genetic and transscriptomic analysis by RNA-seq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-21T15:40:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003663","title":"Massively parallel single-cell B-cell receptor sequencing enables rapid discovery of diverse antigen-reactive antibodies","description":"Using high-throughput single-cell B-cell receptor sequencing (scBCR-seq) we obtained accurately paired full-length heavy- and light-chain variable regions from thousands of individual B cells in a massively parallel fashion. We sequenced more than 250,000 B cells from rat, mouse and human repertoires to characterize their lineages and expansion. In addition, we immunized rats with chicken ovalbumin and profiled antigen-reactive B cells from lymph nodes of immunized animals. The scBCR-seq data recovered 81% (n = 56/69) of B-cell lineages identified from hybridomas generated from the same set of B cells that were subjected to scBCR-seq. Importantly, scBCR-seq identified an additional 710 candidate lineages that were not recovered as hybridomas. We synthesized, expressed and tested 93 clones from the identified lineages and found that 99% (n = 92/93) of the clones were antigen-reactive. Our results establish scBCR-seq as a powerful tool for antibody discovery.","abstract":"Using high-throughput single-cell B-cell receptor sequencing (scBCR-seq) we obtained accurately paired full-length heavy- and light-chain variable regions from thousands of individual B cells in a massively parallel fashion. We sequenced more than 250,000 B cells from rat, mouse and human repertoires to characterize their lineages and expansion. In addition, we immunized rats with chicken ovalbumin and profiled antigen-reactive B cells from lymph nodes of immunized animals. The scBCR-seq data recovered 81% (n = 56/69) of B-cell lineages identified from hybridomas generated from the same set of B cells that were subjected to scBCR-seq. Importantly, scBCR-seq identified an additional 710 candidate lineages that were not recovered as hybridomas. We synthesized, expressed and tested 93 clones from the identified lineages and found that 99% (n = 92/93) of the clones were antigen-reactive. Our results establish scBCR-seq as a powerful tool for antibody discovery.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-22T06:42:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003664","title":"Identifying_and_characterising_the_phenotypic_consequences_of_genetic_perturbation_of_GMPR_in_cellular_models","description":"We have generated human iPSC lines with heterozygous and homozygous knockouts of the GMPR gene through CRISPR/Cas9-mediated genome editing and have successfully differentiated these lines into red blood cells (RBCs).\nTo provide a comprehensive assessment of the phenotypic changes in RBCs derived from engineered hiPSCs we will profile genome-wide gene expression changes using RNA-seq in the edited RBC lines. Transcriptional changes will be measured in 2 lines of each wild-type, heterozygous, and homozygous null deletions of GMPR at day 10 and 15 of erythropoiesis to capture distinct cellular states. For all lines, we will also include the undifferentiated iPSCs as reference. \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We have generated human iPSC lines with monoallelic and biallelic knockouts of the GMPR gene through CRISPR/Cas9-mediated genome editing and have differentiated these lines into erythroblasts. We are in the process of characterising the cellular properties of the lines during erythropoiesis using RNAseq.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003665","title":"Synthetic_RNA_modulators_of_CHD1L_transcription","description":"While the scale of GWAS, and number of discovered loci associated with traits has substantially increased over the past decade, functional validation, and understanding of underlying biology driving these associations has lagged behind; limiting translation of these discoveries into therapeutic applications. In this context, synthetic RNA modulators of gene function provide an efficient, and high-throughput mechanism for validation of discoveries in cellular models, providing a platform for interrogation and translation of findings from GWAS, into therapeutic applications within an integrated platform. An improvement in our understanding of the regulation of gene functions by different types of RNA modulators, and the technological development in the field of synthetic RNA molecules, has enabled high-throughput functional assays of cellular phenotypes in multiple cellular models, as well as opportunities to translate these discoveries directly into therapeutics. Complementary to this, recent development of deep learning approaches to effectively predict miRNA-target associations (Rayner et al., 2017) and promoter regions have provided a rich database of computationally predicted modulators of gene function for functional validation. We propose a high-throughput screen of 380 synthetic RNA molecules across 15 genes identified as associated with cardiometabolic and other traits through multiple lines of evidence (GWAS, eQTL, functional studies, and/or mouse phenotyping). We will use a range of synthetic RNA molecules to target a set of genes of interest in cellular models (HepG2 cell lines), to examine changes in target gene expression (efficacy), immunogenicity and cell-viability. Promoters will be identified through existing databases, and deep learning and bioinformatics approaches; we will also use predicted miRNA-target associations identified through deep learning frameworks trained on experimental evidence (Rayner et al., 2017), as part of an established collaboration. Alongside integrated genetic and EHR data, such datasets provide the opportunity to align multidimensional data to understand loci associated with disease, and identify potential therapeutic targets.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We aim to identify synthetic RNAs targeting the promoter of CHD1L that modulate its expression and that could represent a research and therapeutic tool for the hepatocellular carcinoma characterized by CHD1L overexpression. Gene promoter was identified through existing databases, and deep learning and bioinformatics approaches; we also used predicted miRNA-target associations identified through deep learning frameworks trained on experimental evidence (Rayner et al., 2017), as part of an established collaboration. We carried out a qPCR screen of 28 synthetic RNA molecules and we selected an efficient subset. Through sequencing of  these samples we will  identify the pathways deregulated by CHD1L in the hepatocellular carcinoma (HepG2 cells) revealing mechanisms of carcinogenesis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003666","title":"GDAP___Genome_Diversity_in_Africa_Project","description":"The Genomic Diversity in Africa Project (GDAP) started with the plan to develop a genomic resource from African populations, characterise genomic diversity and population history, and facilitate clinical studies in Africa. Currently, 25 individuals from 24 ethnolinguistic groups have been whole-genome sequenced at high depth totalling 585 individuals. An additional 41 individuals have been sequenced with 10X Genomics libraries. At this stage, the initial curation of this dataset has been finished and we are performing the analysis in coordination with our collaborators. The current state of the GDAP represents a very diverse panel of African populations that maximizes geographical and ethnic variation and represents a great starting point to achieve the aforementioned goals. However, southern sub-Saharan countries, Bantu speakers and hunter gatherer groups are currently underrepresented, despite being crucial to understand the evolutionary history of the continent. After extensive effort to collate studies documentation, we finally have the opportunity to sequence 600 new individuals from these groups, including countries as Gabon, Rwanda and Zambia, and address these deficiencies. We aim to proceed with the same strategy: to sequence at high depth 25 individuals with standard PCR free libraries, with 2 additional individuals with 10X Genomics Chromium libraries per ethnolinguistic group. The former allows a good representation of variants down to low frequency in any given population, and the latter allows accurate phasing and the analysis of structural variation. By including these new populations, we want to investigate three crucial questions in African history in addition to the initial objectives: the Bantu expansion, the evolutionary history of hunter gatherers and the transatlantic slave trade. Additionally, the expanded dataset will help us better discover the genetic variation present in Africa and characterize the African pangenome.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003667","title":"RNA-seq as a tool for evaluating human embryo competence","description":"The majority of embryos that are created through IVF do not implant. One possibility for this inefficiency is an incomplete understanding of the molecular factors affecting embryo competence. Currently, the process of selecting an embryo for uterine transfer utilizes an ad-hoc combination of morphological criteria, the kinetics of development, and genetic testing for aneuploidy. However, no single criterion can ensure selection of a viable embryo. In contrast, RNA-sequencing of embryos could yield highly dimensional data, which may provide additional insight and illuminate the discrepancies among current selection criteria. Indeed, recent advances enabling the production of RNA-sequencing (RNA-seq) libraries from single cells have facilitated the application of this technique to the study of some transcriptional events in early human development. However, these studies have not assessed the quality of their constituent embryos relative to commonly used embryological criteria. Here, we perform proof-of-principle advancement to clinical selection procedures by generating high quality RNA-seq libraries from a trophectoderm biopsy as well as the remaining whole embryo. We combine state-of-the-art embryological methods with low-input RNA-seq to develop the first transcriptome-wide approach for use in future predictive embryology studies. Specifically, we demonstrate the capacity of RNA-seq as a promising tool in preimplantation screening by showing that biopsies of an embryo can capture valuable information content available in the whole embryo from which they are derived. Furthermore, we show that this technique can be used to generate a RNA-based digital karyotype, and to develop a foundational dataset for identifying candidate competence-associated genes. Together, these data establish the foundation for a future RNA-based diagnostic in IVF.","abstract":"The majority of embryos that are created through IVF do not implant. One possibility for this inefficiency is an incomplete understanding of the molecular factors affecting embryo competence. Currently, the process of selecting an embryo for uterine transfer utilizes an ad-hoc combination of morphological criteria, the kinetics of development, and genetic testing for aneuploidy. However, no single criterion can ensure selection of a viable embryo. In contrast, RNA-sequencing of embryos could yield highly dimensional data, which may provide additional insight and illuminate the discrepancies among current selection criteria. Indeed, recent advances enabling the production of RNA-sequencing (RNA-seq) libraries from single cells have facilitated the application of this technique to the study of some transcriptional events in early human development. However, these studies have not assessed the quality of their constituent embryos relative to commonly used embryological criteria. Here, we perform proof-of-principle advancement to clinical selection procedures by generating high quality RNA-seq libraries from a trophectoderm biopsy as well as the remaining whole embryo. We combine state-of-the-art embryological methods with low-input RNA-seq to develop the first transcriptome-wide approach for use in future predictive embryology studies. Specifically, we demonstrate the capacity of RNA-seq as a promising tool in preimplantation screening by showing that biopsies of an embryo can capture valuable information content available in the whole embryo from which they are derived. Furthermore, we show that this technique can be used to generate a RNA-based digital karyotype, and to develop a foundational dataset for identifying candidate competence-associated genes. Together, these data establish the foundation for a future RNA-based diagnostic in IVF.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-23T16:05:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003668","title":"Human monocyte-to-macrophage differentiation involves highly localized gain and loss of DNA methylation at transcription factor binding sites","description":null,"abstract":"Background\nMacrophages and their precursors monocytes play a key role in inflammation and chronic inflammatory disorders. Monocyte-to-macrophage differentiation and activation programs are accompanied by significant epigenetic remodeling where DNA methylation associates with cell identity. Here we show that DNA methylation changes characteristic for monocyte-to-macrophage differentiation occur at transcription factor binding sites, and, in contrast to what was previously described, are generally highly localized and encompass both losses and gains of DNA methylation.\n\nResults\nWe compared genome-wide DNA methylation across 440,292 CpG sites between human monocytes, naïve macrophages and macrophages further activated toward a pro-inflammatory state (using LPS/IFNγ), an anti-inflammatory state (IL-4) or foam cells (oxLDL and acLDL). Moreover, we integrated these data with public whole-genome sequencing data on monocytes and macrophages to demarcate differentially methylated regions. Our analysis showed that differential DNA methylation was most pronounced during monocyte-to-macrophage differentiation, was typically restricted to single CpGs or very short regions and co-localized with lineage-specific enhancers irrespective of whether it concerns gain or loss of methylation. Furthermore, differentially methylated CpGs were located at sites characterized by increased binding of transcription factors known to be involved in monocyte-to-macrophage differentiation including C/EBP and ETS for gain and AP-1 for loss of methylation.\n\nConclusion\nOur study highlights the involvement of subtle, highly localized remodeling of DNA methylation at regulatory regions in cell differentiation.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003669","title":"GDAP___Genome_Diversity_in_Africa_Project","description":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Using a sequencing-based approach, the Genome Diversity in Africa Project (GDAP)  aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003670","title":"Indonesian Genome Diversity Project 2, genotyping data","description":"This study reports Illumina Omni 2.5M genotyping chip data for 48 individuals from Aru, Mentawai, New Guinea and Sumba islands.","abstract":"This study reports Illumina Omni 2.5M genotyping chip data for 48 individuals from Aru, Mentawai, New Guinea and Sumba islands.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-27T09:50:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003671","title":"Indonesian RNA-seq data","description":"Transcription data were collected to study patterns of functional variation across the broad geography of Indonesia. The region has extremely diverse populations, with very different demographic histories and multiple genetic ancestries. This dataset reports high-throughput RNA-sequencing data for individuals from three islands spanning this geographical region: Mentawai, Sumba and West Papua.","abstract":"Transcription data were collected to study patterns of functional variation across the broad geography of Indonesia. The region has extremely diverse populations, with very different demographic histories and multiple genetic ancestries. This dataset reports high-throughput RNA-sequencing data for individuals from three islands spanning this geographical region: Mentawai, Sumba and West Papua.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-27T10:25:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003672","title":"Molecular Profiling Reveals Unique Immune and Metabolic Features of Melanoma Brain Metastases","description":"There is a critical need to improve our understanding of the pathogenesis of -melanoma brain metastases (MBM). Thus, we performed RNA sequencing on 88 resected MBMs and 42 patient-matched extracranial metastases; tumors with sufficient tissue also underwent whole-exome sequencing, T-cell receptor sequencing, and IHC. MBMs demonstrated heterogeneity of immune infiltrates that correlated with prior radiation and post-craniotomy survival. Comparison with patient-matched extracranial metastases identified significant immunosuppression and enrichment of oxidative phosphorylation (OXPHOS) in MBMs. Gene-expression analysis of intracranial and subcutaneous xenografts, and a spontaneous MBM model, confirmed increased OXPHOS gene expression in MBMs, which was also detected by direct metabolite profiling and [U-13C]-glucose tracing in vivo IACS-010759, an OXPHOS inhibitor currently in early-phase clinical trials, improved survival of mice bearing MAPK inhibitor-resistant intracranial melanoma xenografts and inhibited MBM formation in the spontaneous MBM model. The results provide new insights into the pathogenesis and therapeutic resistance of MBMs.","abstract":"There is a critical need to improve our understanding of the pathogenesis of -melanoma brain metastases (MBM). Thus, we performed RNA sequencing on 88 resected MBMs and 42 patient-matched extracranial metastases; tumors with sufficient tissue also underwent whole-exome sequencing, T-cell receptor sequencing, and IHC. MBMs demonstrated heterogeneity of immune infiltrates that correlated with prior radiation and post-craniotomy survival. Comparison with patient-matched extracranial metastases identified significant immunosuppression and enrichment of oxidative phosphorylation (OXPHOS) in MBMs. Gene-expression analysis of intracranial and subcutaneous xenografts, and a spontaneous MBM model, confirmed increased OXPHOS gene expression in MBMs, which was also detected by direct metabolite profiling and [U-13C]-glucose tracing in vivo IACS-010759, an OXPHOS inhibitor currently in early-phase clinical trials, improved survival of mice bearing MAPK inhibitor-resistant intracranial melanoma xenografts and inhibited MBM formation in the spontaneous MBM model. The results provide new insights into the pathogenesis and therapeutic resistance of MBMs.","study_type":"Other","pubmed_ids":[30787016],"external_links":null,"is_released":true,"released_date":"2019-05-27T14:40:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003673","title":"Single-cell TCR sequencing of DQ2.2-glut-L1-specific T cells","description":null,"abstract":"In order to characterize the T cell receptor (TCR) repertoire of DQ2.2-glut-L1-specific T cells, we performed high-throughput DNA sequencing of rearranged TCR-α and TCR-β genes of the single HLA-DQ2.2:DQ2.2-glut-L1 tetramer binding CD4+ T cells isolated from six T-cell lines (TCLs) of four Celiac disease patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-28T11:05:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003674","title":"Single-cell TCR sequencing of DQ2.5-hor-3-specific T cells","description":null,"abstract":"In order to characterize the T cell receptor (TCR) repertoire of DQ2.5-hor-3-specific T cells, we performed high-throughput DNA sequencing of rearranged TCR-α and TCR-β genes of the single HLA-DQ2.5:DQ2.5-hor-3- tetramer binding CD4+ T cells isolated from biopsies of celiac disease patients. We also sequenced the TCR of the T-cell clones (TCCs) that were generated by cloning by limited dilution and antigen-free expansion of HLA-DQ2.5:DQ2.5-hor-3-tetramer binding CD4+ T cells from biopsies of celiac disease patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-28T11:11:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003675","title":"An inborn error of immunity with elevated IgE and hyperinflammation","description":null,"abstract":"A patient presenting with recurrent staphylococcal infections and eczema was whole exome sequenced.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003676","title":"Resident memory CD8 T cells persist for years in human small intestine","description":"Resident memory CD8 T cells (Trm) have been shown to provide effective protective responses in the small intestine (SI) in mice. A better understanding of the generation and persistence of SI CD8 Trm cells in humans may have implications for intestinal immune-mediated diseases and vaccine development. Analyzing normal and transplanted human SI we demonstrated that the majority of SI CD8 T cells were bona fide CD8 Trm cells that survived for over 1 year in the graft. Intraepithelial and lamina propria CD8 Trm cells showed a high clonal overlap and a repertoire dominated by expanded clones, conserved both spatially in the intestine and over time. Functionally, lamina propria CD8 Trm cells were potent cytokine-producers, exhibiting a polyfunctional (IFN-γ+ IL-2+ TNF-α+) profile, and efficiently expressed cytotoxic mediators after stimulation. These results suggest that SI CD8 Trm cells could be relevant targets for future oral vaccines and therapeutic strategies for gut disorders.","abstract":"Resident memory CD8 T cells (Trm) have been shown to provide effective protective responses in the small intestine (SI) in mice. A better understanding of the generation and persistence of SI CD8 Trm cells in humans may have implications for intestinal immune-mediated diseases and vaccine development. Analyzing normal and transplanted human SI we demonstrated that the majority of SI CD8 T cells were bona fide CD8 Trm cells that survived for over 1 year in the graft. Intraepithelial and lamina propria CD8 Trm cells showed a high clonal overlap and a repertoire dominated by expanded clones, conserved both spatially in the intestine and over time. Functionally, lamina propria CD8 Trm cells were potent cytokine-producers, exhibiting a polyfunctional (IFN-γ+ IL-2+ TNF-α+) profile, and efficiently expressed cytotoxic mediators after stimulation. These results suggest that SI CD8 Trm cells could be relevant targets for future oral vaccines and therapeutic strategies for gut disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-28T12:37:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003677","title":"Cellular_phenotyping_of_host_pathogen_interactions","description":"The goal of this project is to understand the etiology and pathology of host-pathogen interaction using high-throughput cellular phenotyping. By combining the expertise in pathogen biology, informatics and stem cell biology across the institute, this project will use targeted genetic modification in mouse embryonic stem cells to identify functions of host genes in innate immunity. We will also explore the biology of mouse embryonic stem cells and their differentiation into immune competent cells. To this end we will generate homozygous and inducible knockout lines in mouse embryonic stem cells, which will be differentiated into immune competent cells, such as macrophages  or dendritic cells. These will be subjected to a panel of immune challenge and stimulation assays to characterise the functions of the disrupted genes. \nTo identify new functions for mammalian genes in innate immunity we will:\n•\tGenerate a panel of homozygous inducible gene knockout mouse ES cell lines working from a list of ca. 80 candidate genes (MGP phenotyping and GWAS hits). \n•\tScale up differentiation protocols for immune challenge and stimulation assays.\n•\tBenchmark in vitro differentiated ES cell models against primary immune cells from selected MGP mouse lines and eventually against human iPS cells.\n•\tScreen a panel of 30 genetically modified cell lines in immunological challenge and stimulation assays, defining phenotypes at the cellular level by high content imaging, biochemically by assaying cytokine production, and at the molecular level by transcriptome analysis.\n•\tDefine novel gene functions in innate immunity through network analysis of gene expression data from all challenged cell lines.\n•\tIn the longer term scale up the production and phenotyping of genetically modified cell lines (mouse or human as appropriate).\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"High-throughput cellular phenotyping to understand the etiology and pathology of host-pathogen interaction.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003678","title":"Presence of bacterial infection in brains of patients with Huntington's disease (HD)","description":"Bacterial isolation in infected brains in patients with Huntington's disease. Here we used next generation sequencing of 16S ribosomal RNA gene PCR amplicons (NGS 16S amplicon analysis)","abstract":"Bacterial isolation in infected brains in patients with Huntington's disease. Here we used next generation sequencing of 16S ribosomal RNA gene PCR amplicons (NGS 16S amplicon analysis)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-30T15:03:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003679","title":"Next Generation Sequencing Characterization of Hematopoietic Stem and Progenitors Cells in Human Systemic Lupus Eryhtematosus","description":null,"abstract":"Purpose: Next-generation sequencing (NGS) technology was exploited to map genome-wide expression profile of hematopoietic stem and progenitor cells (HSPCs) in Systemic Lupus Erythematosus (SLE).\nResults: Transcriptomic analysis of lupus HSPCs indicates activation, displayed increased proliferation and replicative stress, and profoundly prefer to differentiate towards myeloid/granulocytic lineage. Gene expression analysis suggests arrest of differentiation as key regulators including Cebpa, Cebpe, Irf8 are suppressed.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-30T17:19:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003680","title":"Whole exome sequencing for primary lung adenocarcinoma samples","description":"We performed whole exome sequencing (WES) of 11 formalin-fixed paraffin-embedded lung tumour tissues and paired blood samples.","abstract":"We performed whole exome sequencing (WES) of 11 formalin-fixed paraffin-embedded lung tumour tissues and paired blood samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-31T07:45:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003681","title":"Single cell RNA sequencing of lung adenocarcinoma.","description":"We performed single cell RNA sequencing (scRNA-seq) for 208,506 cells derived from 58 lung adenocarcinomas from 44 patients, which covers primary tumour, lymph node and brain metastases, and pleural effusion in addition to normal lung tissues and lymph nodes.","abstract":"We performed single cell RNA sequencing (scRNA-seq) for 208,506 cells derived from 58 lung adenocarcinomas from 44 patients, which covers primary tumour, lymph node and brain metastases, and pleural effusion in addition to normal lung tissues and lymph nodes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-31T07:45:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003682","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___POL___WGS","description":"Somatic mutations (burdens and signatures) and clonal dynamics in individuals with germline DNA polymerase mutations.","abstract":"The aim of this project is to investiagte somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the studyof normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to idnetifiy and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-31T09:49:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003683","title":"Somatic_mutation_and_clonal_evolution_in_the_human_testes___Transcriptome","description":"In this study we aim to characterise the transcriptome landscape and clonal dynamics in normal and cancerous testes and their role in cancer predisposition. We are testing he study combines targeted sequencing and whole-genome sequencing of microbiopsies from testes. The range of patients studied will include healthy individuals, and patients with testicular cancer.","abstract":"In this study we aim to determine the clonal dynamics of spermatogenesis in adult testes and identify factors such as age that affect clonal dynamics.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003684","title":"Control iPSC lines with clinically annotated genetic variants for versatile multi-lineage differentiation","description":"Induced Pluripotent Stem Cells (iPSC) derived from healthy individuals are important controls for disease modeling studies. To create a resource of genetically annotated iPSC, we reprogrammed footprint-free lines from four volunteers in the Personal Genome Project Canada (PGPC). Multilineage directed differentiation efficiently produced functional cortical neurons, cardiomyocytes and hepatocytes. Pilot users further demonstrated line versatility by generating kidney organoids, T-cells and sensory neurons. A frameshift knockout was introduced into MYBPC3 and these cardiomyocytes exhibited a hypertrophic phenotype as expected. WGS annotation of PGPC lines revealed on average 20 coding variants. Importantly, nearly all annotated PGPC and HipSci lines harboured at least one pre-existing or acquired variant with cardiac, neurological or other disease associations. Overall, PGPC lines were efficiently differentiated by multiple users into cell types found in six tissues for disease modelling, and clinical annotation highlighted variant-preferred lines for use as unaffected controls in specific disease settings.","abstract":"Induced Pluripotent Stem Cells (iPSC) derived from healthy individuals are important controls for disease modeling studies. To create a resource of genetically annotated iPSC, we reprogrammed footprint-free lines from four volunteers in the Personal Genome Project Canada (PGPC). Multilineage directed differentiation efficiently produced functional cortical neurons, cardiomyocytes and hepatocytes. Pilot users further demonstrated line versatility by generating kidney organoids, T-cells and sensory neurons. A frameshift knockout was introduced into MYBPC3 and these cardiomyocytes exhibited a hypertrophic phenotype as expected. WGS annotation of PGPC lines revealed on average 20 coding variants. Importantly, nearly all annotated PGPC and HipSci lines harboured at least one pre-existing or acquired variant with cardiac, neurological or other disease associations. Overall, PGPC lines were efficiently differentiated by multiple users into cell types found in six tissues for disease modelling, and clinical annotation highlighted variant-preferred lines for use as unaffected controls in specific disease settings.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-31T14:50:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003685","title":"RNA-sequençing of 21 inflammatory hepatocellular adenomas","description":"The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer). The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors.The present series corresponds to 21 RNA-seq of IHCA samples.\nAligned bam files correspond to hg38 human reference.","abstract":"The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer). The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors.The present series corresponds to 21 RNA-seq of IHCA samples.\nAligned bam files correspond to hg38 human reference.","study_type":"Other","pubmed_ids":[31907296],"external_links":null,"is_released":true,"released_date":"2019-05-31T17:06:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003686","title":"Whole Exome Sequencing of 15 Tumor/Normal pairs of inflammatory hepatocellular adenomas","description":"The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer). The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors. The present series corresponds to 15 Tumor/Normal pairs of Whole Exome Sequencing (WES) of IHCA samples.\nAligned bam files can be both in hg19 (CHC750T/CHC750N; CHC2189T/CHC2189N; CHC2615T/CHC2614N) or hg38 (other samples).","abstract":"The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer). The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors. The present series corresponds to 15 Tumor/Normal pairs of Whole Exome Sequencing (WES) of IHCA samples.\nAligned bam files can be both in hg19 (CHC750T/CHC750N; CHC2189T/CHC2189N; CHC2615T/CHC2614N) or hg38 (other samples).","study_type":"Other","pubmed_ids":[31907296],"external_links":null,"is_released":true,"released_date":"2019-05-31T17:26:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003687","title":"UAMS Smoldering Myeloma Timeline Cohort","description":"To better understand the pattern of genetic changes over time, we performed whole exome sequencing of sequential bone marrow samples from 9 patients taken overtime including some paired SMM/newly diagnosed MM/Relapse MM samples. Samples from 9 patients (9 controls and 53 tumors) underwent whole exome sequencing with an additional capture for the IGH, IHK, IGL, and MYC loci. DNA was obtained from either CD138+ cells from the bone marrow of smoldering myeloma patients through time (tumor) or from stem cell harvests or peripheral blood cells from the same patient (control). 100 ng of DNA was fragmented, end-repaired, and adapters ligated using NimbleGen's MedExome. After PCR amplification hybridized libraries underwent further amplification before being sequenced on a NextSeq500 (Illumina) using 75 bp paired end reads.","abstract":"To better understand the pattern of genetic changes over time, we performed whole exome sequencing of sequential bone marrow samples from 9 patients taken overtime including some paired SMM/newly diagnosed MM/Relapse MM samples. Samples from 9 patients (9 controls and 53 tumors) underwent whole exome sequencing with an additional capture for the IGH, IHK, IGL, and MYC loci. DNA was obtained from either CD138+ cells from the bone marrow of smoldering myeloma patients through time (tumor) or from stem cell harvests or peripheral blood cells from the same patient (control). 100 ng of DNA was fragmented, end-repaired, and adapters ligated using NimbleGen's MedExome. After PCR amplification hybridized libraries underwent further amplification before being sequenced on a NextSeq500 (Illumina) using 75 bp paired end reads.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-05-31T21:22:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003688","title":"HSC_population_dynamics___TG001_2_samples","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-03T16:45:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003689","title":"Large-scale viral genome analysis identifies novel clinical associations between hepatitis B virus and chronically infected patients","description":"Despite the high global prevalence of chronic hepatitis B (CHB) infection, datasets covering the whole hepatitis B viral genome from large patient cohorts are lacking, greatly limiting our understanding of the viral genetic factors involved in this deadly disease. We performed deep sequencing of viral samples from patients chronically infected with HBV to investigate the association between viral genome variation and patients’ clinical characteristics. We discovered novel viral variants strongly associated with viral load and HBeAg status. Patients with viral variants C1817T and A1838G had viral loads nearly three orders of magnitude lower than patients without those variants.  These patients consequently experienced earlier viral suppression while on treatment. Furthermore, we identified novel variants that either independently or in combination with precore mutation G1896A were associated with the transition from HBeAg positive to negative phase of infection. These observations are consistent with the hypothesis that mutation of the HBeAg open reading frame is an important factor driving CHB patient’s HBeAg status. This analysis provides a detailed picture of HBV genetic variation in the largest patient cohort to date and highlights the diversity of plausible molecular mechanisms through which viral variation affects clinical phenotype.","abstract":"Despite the high global prevalence of chronic hepatitis B (CHB) infection, datasets covering the whole hepatitis B viral genome from large patient cohorts are lacking, greatly limiting our understanding of the viral genetic factors involved in this deadly disease. We performed deep sequencing of viral samples from patients chronically infected with HBV to investigate the association between viral genome variation and patients’ clinical characteristics. We discovered novel viral variants strongly associated with viral load and HBeAg status. Patients with viral variants C1817T and A1838G had viral loads nearly three orders of magnitude lower than patients without those variants.  These patients consequently experienced earlier viral suppression while on treatment. Furthermore, we identified novel variants that either independently or in combination with precore mutation G1896A were associated with the transition from HBeAg positive to negative phase of infection. These observations are consistent with the hypothesis that mutation of the HBeAg open reading frame is an important factor driving CHB patient’s HBeAg status. This analysis provides a detailed picture of HBV genetic variation in the largest patient cohort to date and highlights the diversity of plausible molecular mechanisms through which viral variation affects clinical phenotype.","study_type":"Other","pubmed_ids":[31324819],"external_links":null,"is_released":true,"released_date":"2019-06-04T00:50:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003690","title":"Analysis of copy number variation landscape of glioma by shallow coverage whole genome sequencing","description":"We reported shallow coverage whole genome sequencing (WGS) is an economic method for identification of whole genome somatic copy number variation (SCNV). Combining with a Taqman low density array (TLDA) designed for molecular subtyping of glioma, it enabled classification of glioma into biological entities with different cellular origin and genomic alterations. Further, we also showed shallow-coverage WGS enabled systematic identification of clonal and subclonal SCNV in glioma genomes and the burden and pattern of SCNV can serve as an objective marker of tumor progression and predict risk and relapse.","abstract":"We reported shallow coverage whole genome sequencing (WGS) is an economic method for identification of whole genome somatic copy number variation (SCNV). Combining with a Taqman low density array (TLDA) designed for molecular subtyping of glioma, it enabled classification of glioma into biological entities with different cellular origin and genomic alterations. Further, we also showed shallow-coverage WGS enabled systematic identification of clonal and subclonal SCNV in glioma genomes and the burden and pattern of SCNV can serve as an objective marker of tumor progression and predict risk and relapse.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-04T03:39:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003691","title":"Analysis of somatic copy-number variation of glioma by shallow coverage whole genome sequencing.","description":null,"abstract":"We reported shallow coverage whole genome sequencing (WGS) is an economic method for identification of whole genome somatic copy number variation (SCNV). Combining with a Taqman low density array (TLDA) designed for molecular subtyping of glioma, it enabled classification of glioma into biological entities with different cellular origin and genomic alterations. Further, we also showed shallow-coverage WGS enabled systematic identification of clonal and subclonal SCNV in glioma genomes and the burden and pattern of SCNV can serve as an objective marker of tumor progression and predict risk and relapse.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003692","title":"Deciphering_myeloid_landscape_of_non_small_cell_lung_cancer","description":"We will combine state-of-the-art single-cell experimental data generation with computational analysis using novel methods to reveal the full spectrum of transcriptional and epigenetic changes that are associated with myeloid progenitors’ migration and differentiation at the tumour sites. We anticipate that the results from this study will allow characterisation and subdivision of specific MDSC subtypes and provide novel targets to modulate MDSCs accumulation and/or immunosuppressive activity.\n\nThis project will utilise the comprehensive single-cell transcriptome and chromatin accessibility analysis of tumour-associated immune cells, combined with in vitro functional assays, to reveal the molecular programmes that are active during differentiation of myeloid progenitors to myeloid-derived suppressor cells (MDSCs). The results from this study will identify novel targets to modulate accumulation, differentiation and immunosuppressive function of MDSCs and discover new markers for their prospective isolation. Perturbation of MDSCs will provide means to target tumorigenesis and metastases in lung cancer.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We will combine state-of-the-art single-cell experimental data generation with computational analysis using novel methods to reveal the full spectrum of transcriptional and epigenetic changes that are associated with myeloid progenitors’ migration and differentiation at the tumour sites. We anticipate that the results from this study will allow characterisation and subdivision of specific MDSC subtypes and provide novel targets to modulate MDSCs accumulation and/or immunosuppressive activity.\n\nThis project will utilise the comprehensive single-cell transcriptome and chromatin accessibility analysis of tumour-associated immune cells, combined with in vitro functional assays, to reveal the molecular programmes that are active during differentiation of myeloid progenitors to myeloid-derived suppressor cells (MDSCs). The results from this study will identify novel targets to modulate accumulation, differentiation and immunosuppressive function of MDSCs and discover new markers for their prospective isolation. Perturbation of MDSCs will provide means to target tumorigenesis and metastases in lung cancer.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003693","title":"Whole-exome sequencing of lymphomas in immune-privileged sites","description":null,"abstract":"To characterize the genetic alterations in lymphomas in immune-privileged sites, we performed whole-exome sequencing (WES) of 37 primary central nervous system lymphomas (PCNSLs) and 8 primary testicular lymphomas (PTLs). In addition, 6 secondary CNS lymphomas were also subjected to WES, of which 5 patients were also analysed for primary lymphomas.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003694","title":"Whole exome sequencing (WES) of blood cells, single cell and bulk samples","description":"Blood cells (2 T cell types, B cells, granulocytes) and endothelial cells collected from a patient with constitutive DNA repair deficiency and an age- and gender-matched control were whole exome sequenced (WES), with one bulk sample per cell type and patient, and several single cells per cell type and patient. In addition, bulk blood samples of patient and corresponding family were analyzed by WES.","abstract":"Blood cells (2 T cell types, B cells, granulocytes) and endothelial cells collected from a patient with constitutive DNA repair deficiency and an age- and gender-matched control were whole exome sequenced (WES), with one bulk sample per cell type and patient, and several single cells per cell type and patient. In addition, bulk blood samples of patient and corresponding family were analyzed by WES.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003695","title":"Detecting and tracking circulating tumour DNA copy number profiles during first line chemotherapy in oesophagogastric adenocarcinoma","description":"DNA somatic copy number aberrations (SCNAs) are key drivers in oesophago-gastric adenocarcinoma (OGA). Whether minimally invasive SCNA analysis of circulating tumour (ct)DNA can predict treatment outcomes and reveal how SCNAs evolve during chemotherapy is unknown. We investigated this by low-coverage whole genome sequencing (lcWGS) of ctDNA from 30 patients with advanced OGA prior to first-line chemotherapy and on progression.","abstract":"DNA somatic copy number aberrations (SCNAs) are key drivers in oesophago-gastric adenocarcinoma (OGA). Whether minimally invasive SCNA analysis of circulating tumour (ct)DNA can predict treatment outcomes and reveal how SCNAs evolve during chemotherapy is unknown. We investigated this by low-coverage whole genome sequencing (lcWGS) of ctDNA from 30 patients with advanced OGA prior to first-line chemotherapy and on progression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-05T15:15:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003696","title":"Whole-exome sequencing of acute erythroid leukemia","description":"To  clarify the genomic characteristics of acute erythroid leukemia (AEL), 24 AEL cases with matched controls were analyzed using whole exome sequencing. Based on the patterns of genetic alterations, AEL were divided into 4 subgroups. EPOR/JAK/STAT pathway are frequently affected in AEL and could be a therapeutic target.","abstract":"To  clarify the genomic characteristics of acute erythroid leukemia (AEL), 24 AEL cases with matched controls were analyzed using whole exome sequencing. Based on the patterns of genetic alterations, AEL were divided into 4 subgroups. EPOR/JAK/STAT pathway are frequently affected in AEL and could be a therapeutic target.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-06T09:34:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003697","title":"HSC_population_dynamics__scRNA_seq___CB002","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003698","title":"Breast_cancer_topographs","description":"Breast cancer topography will be explored using a combination of multi-region whole geome sequencing  and in-situ RNA sequencing of fixed tissue specimens.","abstract":"Breast cancer topography will be explored using a combination of multi-region whole geome sequencing  and in-situ RNA sequencing of fixed tissue specimens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-07T12:41:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003699","title":"Integrative and comparative genomic analyses identify clinically  relevant groups of pulmonary carcinoids and unveil the supra-carcinoids","description":"Multi-omic data for lung neuroendocrine neoplasms, including the first multi-omic sequencing data for the understudied lung atypical carcinoids. The data includes Whole-exomes, whole-genomes, RNA-seq, and EPIC 850K methylation array data.","abstract":"Multi-omic data for lung neuroendocrine neoplasms, including the first multi-omic sequencing data for the understudied lung atypical carcinoids. The data includes Whole-exomes, whole-genomes, RNA-seq, and EPIC 850K methylation array data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-07T15:49:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003700","title":"GBM cancer stem cell lines -RNA-seq and WGS data","description":"Glioblastoma stem cell lines have been profiled for RNA-seq and WGS","abstract":"Glioblastoma stem cell lines have been profiled for RNA-seq and WGS","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-07T21:06:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003701","title":"Transcriptome Analysis Offers a Comprehensive Illustration of the Genetic Background of Pediatric Acute Myeloid Leukemia","description":null,"abstract":"The objective of this study was to reveal the comprehensive genetic background of pediatric AML. We performed transcriptome analysis (RNA-seq) of 139 patients with de novo pediatric AML who were enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 trial. Fusion genes, correlations between genetic aberrations and clinical information were investigated.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-08T11:12:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003702","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__Oesophageal_adenocarcinoma","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute (40X and 20X depth respectively). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute (40X and 20X depth respectively). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-10T13:22:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003703","title":"Renal_habitat_WXS","description":"This project aims at correlating genetic diversity (as well as transcriptomic, metabolic and immune diversity) observed in multiple targeted tumour biopsies and circulating tumour DNA with heterogeneity on multiparametric MRI. To this end, 20 patients with RCC (15 patients with localised/locally advanced disease and 5 with mRCC) will undergo multiparametric MRI including metabolic assessment by 13C-MRSI as well as measurements of tumour perfusion, oxygenation and water diffusion. Based on unique combinations of these imaging parameters, tumour habitats will be defined through cluster mapping.\n\n Intra-operative biopsy and immediate freezing of tumour cores from different imaging habitats will be performed. Multiregional ex-vivo tumour biopsies will be spatially registered to the MR data by using 3D printed tumour moulds generated from high-resolution volumetric sequences. These moulds allow slicing tumour specimens in identical planes to the MR acquisition and increase the accuracy of tissue sampling. The biopsies will then undergo molecular profiling such as metabolomic and RNA sequencing (including mRNA immune profiling), as well as DNA sequencing to assess driver and clonal mutations in different tumour habitats and guide design of appropriate cfDNA probes. The targeted cfDNA capture panel will be employed to determine the ability of cfDNA to capture the full genetic diversity observed in the primary tumour and to relate cfDNA to various imaging habitats in both renal and pancreatic cancer. Data integration will be undertaken between imaging habitats and molecular profiles for each region.","abstract":"This project aims at correlating genetic diversity (as well as transcriptomic, metabolic and immune diversity) observed in multiple targeted tumour biopsies and circulating tumour DNA with heterogeneity on multiparametric MRI. To this end, 20 patients with RCC (15 patients with localised/locally advanced disease and 5 with mRCC) will undergo multiparametric MRI including metabolic assessment by 13C-MRSI as well as measurements of tumour perfusion, oxygenation and water diffusion. Based on unique combinations of these imaging parameters, tumour habitats will be defined through cluster mapping.\n\n Intra-operative biopsy and immediate freezing of tumour cores from different imaging habitats will be performed. Multiregional ex-vivo tumour biopsies will be spatially registered to the MR data by using 3D printed tumour moulds generated from high-resolution volumetric sequences. These moulds allow slicing tumour specimens in identical planes to the MR acquisition and increase the accuracy of tissue sampling. The biopsies will then undergo molecular profiling such as metabolomic and RNA sequencing (including mRNA immune profiling), as well as DNA sequencing to assess driver and clonal mutations in different tumour habitats and guide design of appropriate cfDNA probes. The targeted cfDNA capture panel will be employed to determine the ability of cfDNA to capture the full genetic diversity observed in the primary tumour and to relate cfDNA to various imaging habitats in both renal and pancreatic cancer. Data integration will be undertaken between imaging habitats and molecular profiles for each region.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-10T13:41:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003704","title":"Renal_habitat_RNA","description":"This project is correlating the molecular profiling of renal tumours with multiparametric and 13C-MRI including by 13C-MRSI.","abstract":"This project aims at correlating genetic diversity (as well as transcriptomic, metabolic and immune diversity) observed in multiple targeted tumour biopsies and circulating tumour DNA with heterogeneity on multiparametric MRI. To this end, 20 patients with RCC (15 patients with localised/locally advanced disease and 5 with mRCC) will undergo multiparametric MRI including metabolic assessment by 13C-MRSI as well as measurements of tumour perfusion, oxygenation and water diffusion. Based on unique combinations of these imaging parameters, tumour habitats will be defined through cluster mapping.\n\n Intra-operative biopsy and immediate freezing of tumour cores from different imaging habitats will be performed. Multiregional ex-vivo tumour biopsies will be spatially registered to the MR data by using 3D printed tumour moulds generated from high-resolution volumetric sequences. These moulds allow slicing tumour specimens in identical planes to the MR acquisition and increase the accuracy of tissue sampling. The biopsies will then undergo molecular profiling such as metabolomic and RNA sequencing (including mRNA immune profiling), as well as DNA sequencing to assess driver and clonal mutations in different tumour habitats and guide design of appropriate cfDNA probes. The targeted cfDNA capture panel will be employed to determine the ability of cfDNA to capture the full genetic diversity observed in the primary tumour and to relate cfDNA to various imaging habitats in both renal and pancreatic cancer. Data integration will be undertaken between imaging habitats and molecular profiles for each region.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-10T13:42:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003705","title":"Multi-layered molecular characterization defines prognostic subtypes of lung adenocarcinoma in Asian never-smokers","description":"Multi-layered genomic studies such as the TCGA project have greatly advanced our understanding on molecular pathogenesis of lung cancer. For Asian nonsmoker patients, however, majority of studies have been limited to mutational analyses, emphasizing ethnic differences in driver mutations (e.g. more frequent EGFR mutations and ALK fusions). In essence, a comprehensive multi-layered characterization that could lead to molecular etiology and patient stratification scheme to be translated into clinical applications for this patient group is still missing. Here we report molecular profiling of tumor and matched normal tissues from 114 non-small-cell lung adenocarcinoma patients using whole exome sequencing, transcriptome sequencing, and array comparative genomic hybridization (CGH).","abstract":"Multi-layered genomic studies such as the TCGA project have greatly advanced our understanding on molecular pathogenesis of lung cancer. For Asian nonsmoker patients, however, majority of studies have been limited to mutational analyses, emphasizing ethnic differences in driver mutations (e.g. more frequent EGFR mutations and ALK fusions). In essence, a comprehensive multi-layered characterization that could lead to molecular etiology and patient stratification scheme to be translated into clinical applications for this patient group is still missing. Here we report molecular profiling of tumor and matched normal tissues from 114 non-small-cell lung adenocarcinoma patients using whole exome sequencing, transcriptome sequencing, and array comparative genomic hybridization (CGH).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-11T08:49:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003706","title":"Analysis of the genomic landscape of chemoresistant multiple myeloma","description":null,"abstract":"The chemoresistant stage of multiple myeloma (MM) is characterized by failure of treatments with proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs). We investigated the somatic mutation and copy number abnormality (CNA) landscape of such double-resistant stage to improve the knowledge of genomic determinants of chemoresistance in MM. Resistant samples showed a higher number of mutations than samples at diagnosis. All samples showed evidence of a complex subclonal architecture. Inactivation of the TP53 gene was the most frequent abnormality, found in 42,5% of patients. KRAS was mutated in 8 patients, NRAS in 5, BRAF in 2 for a total of 15 patients with mutations of the MAPK pathway. The mutations of gene associated with resistance to IMiDs and PIs (e.g. CRBN, IKZF3) were rare and always subclonal. \nThe genomic landscape of double-refractory MM is different from what found at diagnosis, with a higher prevalence of high-risk features and a higher number of gene mutations, suggesting that MM evolves during treatment leading to chemoresistance. Our data suggest that mutation of genes in specific pathways is not a preferred mode of evolution of drug resistance in MM and that chemoresistance of the tumor population is likely attained by a differential but convergent evolution of different subclones that show some level of recurrence but are variable between patients.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003707","title":"Analysis of the genomic landscape of chemoresistant multiple myeloma","description":null,"abstract":"The chemoresistant stage of multiple myeloma (MM) is characterized by failure of treatments with proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs). We investigated the somatic mutation and copy number abnormality (CNA) landscape of such double-resistant stage to improve the knowledge of genomic determinants of chemoresistance in MM. Resistant samples showed a higher number of mutations than samples at diagnosis. All samples showed evidence of a complex subclonal architecture. Inactivation of the TP53 gene was the most frequent abnormality, found in 42,5% of patients. KRAS was mutated in 8 patients, NRAS in 5, BRAF in 2 for a total of 15 patients with mutations of the MAPK pathway. The mutations of gene associated with resistance to IMiDs and PIs (e.g. CRBN, IKZF3) were rare and always subclonal. \nThe genomic landscape of double-refractory MM is different from what found at diagnosis, with a higher prevalence of high-risk features and a higher number of gene mutations, suggesting that MM evolves during treatment leading to chemoresistance. Our data suggest that mutation of genes in specific pathways is not a preferred mode of evolution of drug resistance in MM and that chemoresistance of the tumor population is likely attained by a differential but convergent evolution of different subclones that show some level of recurrence but are variable between patients.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003708","title":"Analysis of the genomic landscape of chemoresistant multiple myeloma","description":null,"abstract":"The chemoresistant stage of multiple myeloma (MM) is characterized by failure of treatments with proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs). We investigated the somatic mutation and copy number abnormality (CNA) landscape of such double-resistant stage to improve the knowledge of genomic determinants of chemoresistance in MM. Resistant samples showed a higher number of mutations than samples at diagnosis. All samples showed evidence of a complex subclonal architecture. Inactivation of the TP53 gene was the most frequent abnormality, found in 42,5% of patients. KRAS was mutated in 8 patients, NRAS in 5, BRAF in 2 for a total of 15 patients with mutations of the MAPK pathway. The mutations of gene associated with resistance to IMiDs and PIs (e.g. CRBN, IKZF3) were rare and always subclonal. \nThe genomic landscape of double-refractory MM is different from what found at diagnosis, with a higher prevalence of high-risk features and a higher number of gene mutations, suggesting that MM evolves during treatment leading to chemoresistance. Our data suggest that mutation of genes in specific pathways is not a preferred mode of evolution of drug resistance in MM and that chemoresistance of the tumor population is likely attained by a differential but convergent evolution of different subclones that show some level of recurrence but are variable between patients.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003709","title":"Analysis of the genomic landscape of chemoresistant multiple myeloma","description":null,"abstract":"The chemoresistant stage of multiple myeloma (MM) is characterized by failure of treatments with proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs). We investigated the somatic mutation and copy number abnormality (CNA) landscape of such double-resistant stage to improve the knowledge of genomic determinants of chemoresistance in MM.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-11T15:04:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003710","title":"The 3D evolution of glioma cell populations","description":"Study description: A detailed understanding of heterogeneity in solid tumors has been limited due to insufficient sampling and a lack of knowledge from where within the tumor the sample was taken from. We present here a novel resource - the 3D Glioma Atlas -  in which we record the precise, three-dimensional (3D) coordinate for each of 8-20 spatially-distinct samples obtained from each patient tumor.By revealing how genetic alterations and tumor cell states are patterned in glioma in 3D space, our Atlas shows that genetic diversity is more regionally confined in indolent as compared to aggressive tumors, that recurrent tumors have a greater density of genetic diversity, and that more aggressive tumors have greater tumor-wide transcriptomic heterogeneity.","abstract":"Study description: A detailed understanding of heterogeneity in solid tumors has been limited due to insufficient sampling and a lack of knowledge from where within the tumor the sample was taken from. We present here a novel resource - the 3D Glioma Atlas -  in which we record the precise, three-dimensional (3D) coordinate for each of 8-20 spatially-distinct samples obtained from each patient tumor.By revealing how genetic alterations and tumor cell states are patterned in glioma in 3D space, our Atlas shows that genetic diversity is more regionally confined in indolent as compared to aggressive tumors, that recurrent tumors have a greater density of genetic diversity, and that more aggressive tumors have greater tumor-wide transcriptomic heterogeneity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-12T19:52:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003711","title":"ID1 in glioblastoma","description":null,"abstract":"Glioblastoma is the most common primary brain tumor in adults. While the introduction of temozolomide chemotherapy has increased long-term survivorship, treatment failure and rapid tumor recurrence remains universal. The transcriptional regulatory protein, inhibitor of DNA-binding-1 (ID1), is a key regulator of cell phenotype in cancer. We show that CRISPR-mediated knockout of ID1 in glioblastoma cells, breast adenocarcinoma cells, and melanoma cells, dramatically reduced tumor progression in all three cancer systems through transcriptional downregulation of EGF, which resulted in decreased EGFR phosphorylation. Moreover, ID1-positive cells were enriched by chemotherapy and drove tumor recurrence in glioblastoma. Addition of the neuroleptic drug pimozide to inhibit ID1 expression enhanced the cytotoxic effects of temozolomide therapy on glioma cells and significantly prolonged time to tumor recurrence. Conclusively, this data suggests ID1 could be a promising therapeutic target in patients with glioblastoma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-13T05:42:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003712","title":"Sequecning of the mitochondrial genome of patients with mitochondrial disorders using Oxford Nanopore Technologies long read sequencing","description":null,"abstract":"This study aims to assess the utility of Oxford Nanopore Technology in the clinical diagnostics of mitochondrial genetic disorders by comparing to current techniques like Southern blotting and short read sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003713","title":"From matrimonial practices to genetic diversity in SouthEast Asian populations","description":null,"abstract":"From matrimonial practices to genetic diversity in SouthEast Asian populations","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003714","title":"Infant Glioma Molecular Subtype","description":"Infant gliomas have completely different clinical behavior than gliomas in children and adults. Low-grade tumors are more aggressive with a higher mortality rate, while high-grade tumors are more benign. However, we have little understanding of their biology and so cannot explain this behavior and what constitutes optimal clinical management. To solve this enigma, we performed a comprehensive genetic analysis of the largest cohort to date of infantile gliomas. We uncovered several important findings which dramatically change the management of these cancers. Infant hemispheric gliomas harbor unique alterations in ROS, ALK, MET and other genes found in adult carcinomas. Unlike in adults, they are typically the only alteration present and some of these tumors regress from high- to low-grade partially explaining their favorable clinical outcome. Midline gliomas harbor RAS/MAPK pathway mutations, progress rapidly, and do not respond to current chemoradiation approaches, partially explaining their poorer outcome. These data suggest that infant gliomas require different therapeutic approaches including early use of targeted therapies.","abstract":"Infant gliomas have completely different clinical behavior than gliomas in children and adults. Low-grade tumors are more aggressive with a higher mortality rate, while high-grade tumors are more benign. However, we have little understanding of their biology and so cannot explain this behavior and what constitutes optimal clinical management. To solve this enigma, we performed a comprehensive genetic analysis of the largest cohort to date of infantile gliomas. We uncovered several important findings which dramatically change the management of these cancers. Infant hemispheric gliomas harbor unique alterations in ROS, ALK, MET and other genes found in adult carcinomas. Unlike in adults, they are typically the only alteration present and some of these tumors regress from high- to low-grade partially explaining their favorable clinical outcome. Midline gliomas harbor RAS/MAPK pathway mutations, progress rapidly, and do not respond to current chemoradiation approaches, partially explaining their poorer outcome. These data suggest that infant gliomas require different therapeutic approaches including early use of targeted therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-13T14:15:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003715","title":"Characterization of patient-derived xenograft models of myxoid liposarcoma either sentitive or resistant to trabectedin","description":"Two patient-derived xenograft model of myxoid liposarcoma one sensitive and one resistant to trabectedin. The aim of the study was to study the resistance to the drug.","abstract":"Two patient-derived xenograft model of myxoid liposarcoma one sensitive and one resistant to trabectedin. The aim of the study was to study the resistance to the drug.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-13T21:27:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003716","title":"Deciphering_myeloid_landscape_of_non_small_cell_lung_cancer","description":"We will combine state-of-the-art single-cell experimental data generation with computational analysis using novel methods to reveal the full spectrum of transcriptional and epigenetic changes that are associated with myeloid progenitors’ migration and differentiation at the tumour sites. We anticipate that the results from this study will allow characterisation and subdivision of specific MDSC subtypes and provide novel targets to modulate MDSCs accumulation and/or immunosuppressive activity.\n\nThis project will utilise the comprehensive single-cell transcriptome and chromatin accessibility analysis of tumour-associated immune cells, combined with in vitro functional assays, to reveal the molecular programmes that are active during differentiation of myeloid progenitors to myeloid-derived suppressor cells (MDSCs). The results from this study will identify novel targets to modulate accumulation, differentiation and immunosuppressive function of MDSCs and discover new markers for their prospective isolation. Perturbation of MDSCs will provide means to target tumorigenesis and metastases in lung cancer. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We will combine state-of-the-art single-cell experimental data generation with computational analysis using novel methods to reveal the full spectrum of transcriptional and epigenetic changes that are associated with myeloid progenitors’ migration and differentiation at the tumour sites. We anticipate that the results from this study will allow characterisation and subdivision of specific MDSC subtypes and provide novel targets to modulate MDSCs accumulation and/or immunosuppressive activity.\n\nThis project will utilise the comprehensive single-cell transcriptome and chromatin accessibility analysis of tumour-associated immune cells, combined with in vitro functional assays, to reveal the molecular programmes that are active during differentiation of myeloid progenitors to myeloid-derived suppressor cells (MDSCs). The results from this study will identify novel targets to modulate accumulation, differentiation and immunosuppressive function of MDSCs and discover new markers for their prospective isolation. Perturbation of MDSCs will provide means to target tumorigenesis and metastases in lung cancer. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003717","title":"Targeted resequencing of FECH in EPP patients","description":null,"abstract":"Purpose\nExisting data do not explain the reason why some individuals homozygous for the hypomorphic FECH allele develop erythropoietic protoporphyria (EPP) while the majority are completely asymptomatic. This study aims to identify novel possible genetic variants contributing to this variable phenotype. \nMethods\nHigh throughput re-sequencing of the FECH gene, qualitative analysis of RNA and quantitative DNA methylation examination were performed on a cohort of 72 subjects. \nResults \nA novel deep intronic variant was found in four homozygous carriers developing a clinically overt disease. We demonstrate that this genetic variant leads to the insertion of a pseudoexon containing a stop codon in the mature FECH transcript by the abolition of an exonic splicing silencer site and the concurrent institution of a new methylated CpG di-nucleotide. Moreover, we show that the hypomorphic FECH allele is linked to a single haplotype of about 20kb in size that encompasses three non-coding variants that were previously associated with expression quantitative trait loci (eQTLs).\nConclusion \nThis study confirms that intronic variants could explain the variability in the clinical manifestations of EPP. Moreover, it supports the hypothesis that the control of the FECH gene expression can be mediated through a methylation-dependent modulation of the pre-mRNA splicing pattern.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003718","title":"Genomic landscape of chemoresistant multiple myeloma","description":"The chemoresistant stage of multiple myeloma (MM) is characterized by failure of treatments with proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs). We investigated the somatic mutation and copy number abnormality (CNA) landscape of such double-resistant stage to improve the knowledge of genomic determinants of chemoresistance in MM.","abstract":"The chemoresistant stage of multiple myeloma (MM) is characterized by failure of treatments with proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs). We investigated the somatic mutation and copy number abnormality (CNA) landscape of such double-resistant stage to improve the knowledge of genomic determinants of chemoresistance in MM.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003719","title":"Sporadic and endemic Burkitt lymphoma have frequent FOXO1 mutations but distinct hotspots in the AKT recognition motif","description":"FOXO1 has an oncogenic role in adult germinal center derived lymphomas, in which mutations, predominately within the AKT recognition motif, cause nuclear retention of FOXO1 resulting in increased cell proliferation. To determine the prevalence and distribution of FOXO1 mutations in pediatric Burkitt lymphoma (BL), we sequenced a large number of sporadic and endemic BL patient samples. We report a high frequency of FOXO1 mutations in both sporadic and endemic BL at diagnosis, occurring in 23/78 (29%) and 48/89 (54%) samples respectively, as well as 8/16 (50%) cases at relapse. Mutations of T24 were the most common in sporadic BL but were rare in endemic cases, in which mutations of residue S22, also within the AKT recognition motif, were the most frequent. FOXO1 mutations were almost always present in the major tumor cell clone but were not associated with outcome. Analysis of other recurrent mutations reported in BL revealed that FOXO1 mutations were associated with mutations of DDX3X and ARID1A, but not MYC, TCF3/ID3 or members of the phosphatidylinositol 3’ OH kinase (PI3K) signaling pathway. We further show common nuclear retention of the FOXO1 protein, irrespective of mutation status, suggesting alternative unknown mechanisms for maintaining FOXO1 transcriptional activity in BL. CRISPR/Cas9 knockout of FOXO1 in an endemic cell line produced a significant decrease in cell proliferation, supporting an oncogenic role for FOXO1 in endemic BL. Thus, FOXO1 is frequently mutated in both sporadic and endemic BL and may offer a potential therapeutic target for pediatric BL patients worldwide.","abstract":"FOXO1 has an oncogenic role in adult germinal center derived lymphomas, in which mutations, predominately within the AKT recognition motif, cause nuclear retention of FOXO1 resulting in increased cell proliferation. To determine the prevalence and distribution of FOXO1 mutations in pediatric Burkitt lymphoma (BL), we sequenced a large number of sporadic and endemic BL patient samples. We report a high frequency of FOXO1 mutations in both sporadic and endemic BL at diagnosis, occurring in 23/78 (29%) and 48/89 (54%) samples respectively, as well as 8/16 (50%) cases at relapse. Mutations of T24 were the most common in sporadic BL but were rare in endemic cases, in which mutations of residue S22, also within the AKT recognition motif, were the most frequent. FOXO1 mutations were almost always present in the major tumor cell clone but were not associated with outcome. Analysis of other recurrent mutations reported in BL revealed that FOXO1 mutations were associated with mutations of DDX3X and ARID1A, but not MYC, TCF3/ID3 or members of the phosphatidylinositol 3’ OH kinase (PI3K) signaling pathway. We further show common nuclear retention of the FOXO1 protein, irrespective of mutation status, suggesting alternative unknown mechanisms for maintaining FOXO1 transcriptional activity in BL. CRISPR/Cas9 knockout of FOXO1 in an endemic cell line produced a significant decrease in cell proliferation, supporting an oncogenic role for FOXO1 in endemic BL. Thus, FOXO1 is frequently mutated in both sporadic and endemic BL and may offer a potential therapeutic target for pediatric BL patients worldwide.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-18T13:49:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003720","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___APPENDIX___WES","description":"Somatic mutations (burdens and signatures) and clonal dynamics in normal appendix tissue.","abstract":"The aim of this project is to investigate somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the study of normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to identify and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-18T15:17:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003721","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___APPENDIX___WGS","description":"Somatic mutations (burdens and signatures) and clonal dynamics in normal appendix tissue.","abstract":"The aim of this project is to investigate somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the study of normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to identify and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003722","title":"Exome and Whole-Genome Sequencing of Central African Hunter-Gatherers and Agriculturalists","description":"To investigate how human populations have adapted to the equatorial rainforest, we generated 266 high-coverage exomes, analyzed in combination with 300 published exomes, from 14 populations of African rainforest hunter-gatherers and farmers, together with 40 newly-generated, low-coverage genomes. Genome scans for positive selection and signatures of polygenic selection provide evidence for local adaptation of hunter-gatherers to the African rainforest.","abstract":"To investigate how human populations have adapted to the equatorial rainforest, we generated 266 high-coverage exomes, analyzed in combination with 300 published exomes, from 14 populations of African rainforest hunter-gatherers and farmers, together with 40 newly-generated, low-coverage genomes. Genome scans for positive selection and signatures of polygenic selection provide evidence for local adaptation of hunter-gatherers to the African rainforest.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-19T07:36:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003723","title":"Cancer and germline exomes consisting of FASTQ paired-end reads from melanoma and lung cancer samples","description":"Efforts to precisely identify tumor human leukocyte antigen presented peptides (HLAp) capable of mediating T cell based tumor rejection still face important challenges. Recent reports suggest that non-canonical cancer HLAp could be immunogenic but their identification requires highly sensitive and accurate mass-spectrometry (MS)-based proteogenomics approaches. Here, we present a MS-based analytical pipeline that can precisely characterize the non-canonical HLAp repertoire, incorporating whole exome sequencing, bulk and single cell transcriptomics, ribosome profiling, and a combination of two MS/MS search tools. This approach results in the accurate identification of hundreds of shared and tumor-specific non-canonical HLAp. Albeit often at low levels and in distinct subpopulations of cells, numerous non-canonical HLAp are shared across tumors. This analytical platform holds great promise for the discovery of novel cancer antigens for cancer immunotherapy.","abstract":"Efforts to precisely identify tumor human leukocyte antigen presented peptides (HLAp) capable of mediating T cell based tumor rejection still face important challenges. Recent reports suggest that non-canonical cancer HLAp could be immunogenic but their identification requires highly sensitive and accurate mass-spectrometry (MS)-based proteogenomics approaches. Here, we present a MS-based analytical pipeline that can precisely characterize the non-canonical HLAp repertoire, incorporating whole exome sequencing, bulk and single cell transcriptomics, ribosome profiling, and a combination of two MS/MS search tools. This approach results in the accurate identification of hundreds of shared and tumor-specific non-canonical HLAp. Albeit often at low levels and in distinct subpopulations of cells, numerous non-canonical HLAp are shared across tumors. This analytical platform holds great promise for the discovery of novel cancer antigens for cancer immunotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-19T10:26:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003724","title":"RNA-seq consisting of FASTQ paired-end reads from cancer samples","description":"Efforts to precisely identify tumor human leukocyte antigen presented peptides (HLAp) capable of mediating T cell based tumor rejection still face important challenges. Recent reports suggest that non-canonical cancer HLAp could be immunogenic but their identification requires highly sensitive and accurate mass-spectrometry (MS)-based proteogenomics approaches. Here, we present a MS-based analytical pipeline that can precisely characterize the non-canonical HLAp repertoire, incorporating whole exome sequencing, bulk and single cell transcriptomics, ribosome profiling, and a combination of two MS/MS search tools. This approach results in the accurate identification of hundreds of shared and tumor-specific non-canonical HLAp. Albeit often at low levels and in distinct subpopulations of cells, numerous non-canonical HLAp are shared across tumors. This analytical platform holds great promise for the discovery of novel cancer antigens for cancer immunotherapy.","abstract":"Efforts to precisely identify tumor human leukocyte antigen presented peptides (HLAp) capable of mediating T cell based tumor rejection still face important challenges. Recent reports suggest that non-canonical cancer HLAp could be immunogenic but their identification requires highly sensitive and accurate mass-spectrometry (MS)-based proteogenomics approaches. Here, we present a MS-based analytical pipeline that can precisely characterize the non-canonical HLAp repertoire, incorporating whole exome sequencing, bulk and single cell transcriptomics, ribosome profiling, and a combination of two MS/MS search tools. This approach results in the accurate identification of hundreds of shared and tumor-specific non-canonical HLAp. Albeit often at low levels and in distinct subpopulations of cells, numerous non-canonical HLAp are shared across tumors. This analytical platform holds great promise for the discovery of novel cancer antigens for cancer immunotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-19T10:26:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003725","title":"Human adipose tissue immune cells","description":"We describe a novel and conserved Trem2+ lipid-associated macrophage (LAM) subset and identify markers, spatial localization, origin, and functional pathways associated with these cells. Genetic ablation of Trem2 in mice globally inhibits the downstream molecular LAM program, leading to adipocyte hypertrophy as well as systemic hypercholesterolemia, body fat accumulation, and glucose intolerance. These findings identify Trem2 signaling as a major pathway by which macrophages respond to loss of tissue-level lipid homeostasis, highlighting Trem2 as a key sensor of metabolic pathologies across multiple tissues and a potential therapeutic target in metabolic diseases.","abstract":"We describe a novel and conserved Trem2+ lipid-associated macrophage (LAM) subset and identify markers, spatial localization, origin, and functional pathways associated with these cells. Genetic ablation of Trem2 in mice globally inhibits the downstream molecular LAM program, leading to adipocyte hypertrophy as well as systemic hypercholesterolemia, body fat accumulation, and glucose intolerance. These findings identify Trem2 signaling as a major pathway by which macrophages respond to loss of tissue-level lipid homeostasis, highlighting Trem2 as a key sensor of metabolic pathologies across multiple tissues and a potential therapeutic target in metabolic diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-20T09:30:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003726","title":"RNA Sequencing of paediatric patients with B lymphoblastic leukemia","description":null,"abstract":"RNA sequencing is a powerful tool to study the genetic subtype of acute lymphoblastic leukemias. In this study, we performed whole transcriptome mRNA Sequencing on a cohort of paediatric patients with B-lymphoblastic leukemia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-20T18:31:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003727","title":"From matrimonial practices to genetic diversity in Southeast Asian populations: the signature of the matrilineal puzzle","description":"This project aims at revisiting the \"matrilineal puzzle\" from a population genetics' point of view.\nThe dataset consists of 719 individuals from 12 populations sampled in continental Southeast Asia and genotyped at 598764 loci. This dataset can only be accessed and used for non-commercial research purposes with a finality complying with the informed consent provided by donors.\nFor accessing the data, please provide:\n1. An explicit title for the project you wish to use the data for.\n2. A detailed institutional affiliation of all recipients and users of the data.\n3. A summary (500 words) of the research project, with emphasis on its scientific and societal finality, and predicted outputs.\nIf access is granted by the DAC, data cannot be shared with a third party not initially involved in the project, without the third party officially applying for accessing the data.","abstract":"This project aims at revisiting the \"matrilineal puzzle\" from a population genetics' point of view.\nThe dataset consists of 719 individuals from 12 populations sampled in continental Southeast Asia and genotyped at 598764 loci. This dataset can only be accessed and used for non-commercial research purposes with a finality complying with the informed consent provided by donors.\nFor accessing the data, please provide:\n1. An explicit title for the project you wish to use the data for.\n2. A detailed institutional affiliation of all recipients and users of the data.\n3. A summary (500 words) of the research project, with emphasis on its scientific and societal finality, and predicted outputs.\nIf access is granted by the DAC, data cannot be shared with a third party not initially involved in the project, without the third party officially applying for accessing the data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-21T10:31:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003728","title":"Human pan-genome analysis data","description":null,"abstract":"The reference human genome is still incomplete, and several non-reference sequences have derived from diverse populations. With the available of whole genome sequencing data from multiple individuals, we could construct the pan-genome sequence. Here we provide high quality genome sequencing (~30x coverage) from 185 Han Chinese individuals. All samples were sequenced using Illumina HiSeq X10 sequencer and paired-end 150-bp reads were produced.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003729","title":"miRNA expression by RNAseq in bronchial biopsies of asthmatics, asthma in remission and healthy subjects","description":null,"abstract":"The study focus was differential expression of miRNAs in bronchial biopsies between persistent asthma, asthma in remission and healthy controls using RNAseq.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003730","title":"Genomic, transcriptomic and epigenomic profiling of GCTB","description":"Giant cell tumor of bone is a rare bone neoplasm driven by oncogenic hotspot G34W/L/V mutations in the non-canonical histone variant H3.3. This study provides primary data of genomic (WGS), transcriptomic (RNA-seq) and epigenomic (histone mark ChIP-seq, WGBS, ATAC-seq) profiling of primary GCTB samples from several cohorts in Germany and Korea. We confirm the H3.3-G34 mutations as sole genetic drivers of GCTB, and describe the epigenetic alterations in mutant GCTB stromal cells.","abstract":"Giant cell tumor of bone is a rare bone neoplasm driven by oncogenic hotspot G34W/L/V mutations in the non-canonical histone variant H3.3. This study provides primary data of genomic (WGS), transcriptomic (RNA-seq) and epigenomic (histone mark ChIP-seq, WGBS, ATAC-seq) profiling of primary GCTB samples from several cohorts in Germany and Korea. We confirm the H3.3-G34 mutations as sole genetic drivers of GCTB, and describe the epigenetic alterations in mutant GCTB stromal cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-26T12:22:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003731","title":"DNA Methylation loss coupled with mitotic cell division promotes immune evasion of tumours with high mutation load","description":"Mitotic cell division increases tumour mutation burden and copy number load with a positive and inverse correlation, respectively, with the clinical benefit of immunotherapy. Markers of cell division correlate also with genomic demethylation involving methylation loss in late-replicating partial methylation domains. Here we find that immunomodulatory pathway genes are concentrated in these domains and transcriptionally repressed in demethylated tumours with CpG island promoter hypermethylation. Global methylation loss correlated with immune evasion signatures independently of mutation burden and aneuploidy. Methylome data of our cohort (n = 60) and a published cohort (n = 81) in lung cancer and a melanoma cohort (n = 40) consistently demonstrated that genomic methylation alterations counteract the contribution of high mutation burden and increase immunotherapeutic resistance. Higher predictive power was observed for methylation loss than mutation burden. We also found that genomic hypomethylation correlates with the immune escape signatures of aneuploid tumours. Hence, DNA methylation alterations implicate epigenetic modulation as a combination regimens for precision immunotherapy.","abstract":"Mitotic cell division increases tumour mutation burden and copy number load with a positive and inverse correlation, respectively, with the clinical benefit of immunotherapy. Markers of cell division correlate also with genomic demethylation involving methylation loss in late-replicating partial methylation domains. Here we find that immunomodulatory pathway genes are concentrated in these domains and transcriptionally repressed in demethylated tumours with CpG island promoter hypermethylation. Global methylation loss correlated with immune evasion signatures independently of mutation burden and aneuploidy. Methylome data of our cohort (n = 60) and a published cohort (n = 81) in lung cancer and a melanoma cohort (n = 40) consistently demonstrated that genomic methylation alterations counteract the contribution of high mutation burden and increase immunotherapeutic resistance. Higher predictive power was observed for methylation loss than mutation burden. We also found that genomic hypomethylation correlates with the immune escape signatures of aneuploid tumours. Hence, DNA methylation alterations implicate epigenetic modulation as a combination regimens for precision immunotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-26T14:08:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003732","title":"Measuring minimal residual disease in acute myeloid leukemia with MASQ","description":null,"abstract":"Measuring minimal residual disease (MRD) in cancer has clinical applications for prognosis, monitoring treatment, and detection of recurrence. Simple sequence-based methods to detect nucleotide substitution variants have error rates (about 10^-3) that limit sensitive detection. We developed and characterize the performance of MASQ (Multiplex Accurate Sensitive Quantitation), a method with an error rate on the order of 10^-6. MASQ counts variant templates accurately in the presence of millions of host genomes by using tags to identify each template and demanding consensus over multiple reads of each template. At least 50 target loci can be multiplexed and quantified accurately over a wide range of genomic DNA input amounts. Simultaneously assaying many target variants allows for efficient use of sample, high sensitivity, robustness, and the ability to distinguish subpopulations of variants. We tested MASQ in a small pilot study measuring residual disease in acute myeloid leukemia (AML) patients who entered remission following induction therapy. We detect leukemic variants in the blood and bone marrow samples of all five patients, after induction therapy. We observe evidence of subclonal structure following treatment and find higher target variant frequencies in patients who go on to relapse.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-26T15:12:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003733","title":"Analysis of mechanisms of CD19- relapse following novel low affinity CD19 Chimeric Antigen Receptor (CAR) T-cells (CD19 CAR T-cells) in a Phase I clinical study in paediatric ALL: CARPALL","description":"Phase I clinical study (CARPALL, NCT02443831) utilizing a novel low affinity CD19CAR CAR in patients age &lt;25 with high risk CD19+ ALL. Seventeen patients were enrolled and 14 received an infusion of CAR T cells. Among those achieving complete remission, 6 subsequently relapsed, 5 with CD19- disease, 1 with CD19+ disease. Whole exome sequencing of bone marrow DNA from patients with CD19- relapse showed mutations in the CD19 gene predicted to result in loss of surface expression in 4/5 patients. These mutations were not detectable prior to CAR T cell therapy. With a median follow-up of 14 months, 5/14 patients (36%) are alive and disease-free. Overall survival was 84% at 6 months and 63% at 12 months and by the criteria used in the ELIANA study, event-free survival was 67% and 46%. Using more stringent criteria where an event is defined as molecular relapse, molecular EFS was 55% and 29 %. The median duration of remission in responding patients was 7.4 months.","abstract":"Phase I clinical study (CARPALL, NCT02443831) utilizing a novel low affinity CD19CAR CAR in patients age &lt;25 with high risk CD19+ ALL. Seventeen patients were enrolled and 14 received an infusion of CAR T cells. Among those achieving complete remission, 6 subsequently relapsed, 5 with CD19- disease, 1 with CD19+ disease. Whole exome sequencing of bone marrow DNA from patients with CD19- relapse showed mutations in the CD19 gene predicted to result in loss of surface expression in 4/5 patients. These mutations were not detectable prior to CAR T cell therapy. With a median follow-up of 14 months, 5/14 patients (36%) are alive and disease-free. Overall survival was 84% at 6 months and 63% at 12 months and by the criteria used in the ELIANA study, event-free survival was 67% and 46%. Using more stringent criteria where an event is defined as molecular relapse, molecular EFS was 55% and 29 %. The median duration of remission in responding patients was 7.4 months.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-26T22:02:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003734","title":"CD3 bispecific antibody-induced cytokine release is dispensable for cytotoxic T cell activity","description":null,"abstract":"T cell activating therapies are commonly accompanied by systemic cytokine release, which can progress\nto deadly cytokine release syndrome (CRS). Herein, we describe that T cell triggering by anti-HER2/CD3\nbispecific antibody induces systemic toxic cytokine release form monocytes/macrophages. We\ndemonstrate that T cell-generated TNFa is the primary mechanism mediating monocyte activation and\nthat prevention of TNFa release is sufficient to impair systemic release of monocyte cytokines without\naffecting anti-tumor efficacy. The mechanistic uncoupling of toxic cytokines and T cell cytolytic activity in\nthe context of CD3 bispecifics provides strong biological rationale to clinically explore preventative\ntreatment approaches to mitigate toxicity.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-27T00:32:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003735","title":"Gene expression by RNAseq in bronchial biopsies of asthmatics, asthma in remission and healthy subjects","description":"The study focus was differential expression in bronchial biopsies between persistent asthma, asthma in remission and healthy controls using RNAseq.","abstract":"The study focus was differential expression in bronchial biopsies between persistent asthma, asthma in remission and healthy controls using RNAseq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-27T10:19:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003736","title":"Germline mutations in the transcription factor IKZF5 cause thrombocytopenia.","description":"To identify novel causes of hereditary thrombocytopenia, we performed a genetic association analysis of whole-genome sequencing data from 13,037 individuals enrolled in the NIHR BioResource, including 233 cases with isolated thrombocytopenia. We found an association between rare variants in the transcription factor encoding gene IKZF5 and thrombocytopenia. We report five causal missense variants in or near IKZF5 zinc fingers (Znfs), of which two occurred de novo and three co-segregated in three pedigrees. A canonical DNA-Znf binding model predicts that three of the variants alter DNA recognition. Expression studies showed that chromatin binding was disrupted in mutant compared to wild-type (WT) IKZF5 and electron microscopy revealed a reduced quantity of alpha granules in normally sized platelets. Proplatelet formation (PPF) was reduced in megakaryocytes (MKs) from seven cases relative to six controls. Comparison of RNA-seq data from platelets, monocytes, neutrophils and CD4 T-cells from three cases and 14 healthy controls showed 1,194 differentially expressed genes in platelets but only four DEGs in each of the other blood cell types. In conclusion, IKZF5 is a novel transcriptional regulator of megakaryopoiesis and the eighth transcription factor associated with dominant thrombocytopenia in humans.","abstract":"To identify novel causes of hereditary thrombocytopenia, we performed a genetic association analysis of whole-genome sequencing data from 13,037 individuals enrolled in the NIHR BioResource, including 233 cases with isolated thrombocytopenia. We found an association between rare variants in the transcription factor encoding gene IKZF5 and thrombocytopenia. We report five causal missense variants in or near IKZF5 zinc fingers (Znfs), of which two occurred de novo and three co-segregated in three pedigrees. A canonical DNA-Znf binding model predicts that three of the variants alter DNA recognition. Expression studies showed that chromatin binding was disrupted in mutant compared to wild-type (WT) IKZF5 and electron microscopy revealed a reduced quantity of alpha granules in normally sized platelets. Proplatelet formation (PPF) was reduced in megakaryocytes (MKs) from seven cases relative to six controls. Comparison of RNA-seq data from platelets, monocytes, neutrophils and CD4 T-cells from three cases and 14 healthy controls showed 1,194 differentially expressed genes in platelets but only four DEGs in each of the other blood cell types. In conclusion, IKZF5 is a novel transcriptional regulator of megakaryopoiesis and the eighth transcription factor associated with dominant thrombocytopenia in humans.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-27T14:41:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003737","title":"A targeted gene panel that covers coding, noncoding, and short tandem repeat regions improves the diagnosis of patients with neurodegenerative diseases","description":"Genetic testing for diagnosis of neurodegenerative diseases (NDs) is highly challenging because of genotype heterogeneity and overlapping clinical manifestations. Targeted-gene panels (TGPs), coupled with next-generation sequencing (NGS), can facilitate the profiling of a large repertoire of ND-related genes and help with differential diagnosis. Due to the technical limitations inherent in NGS and TGPs, short tandem repeat (STR) variations are often ignored. However, STR expansions are known to cause such NDs as Huntington’s disease and several types of spinocerebellar ataxias, such as SCA type 3 (SCA3).Here, we studied the clinical utility of a custom-made TGP that targets 199 NDs and 311 ND-associated genes on 118 undiagnosed patients. At least one known pathogenic or likely pathogenic variation was found in 54 (45.8%) patients; 27 (22.9%) of the 118 patients demonstrated clinical profiles that matched the variants. Based on the findings from the TGP, we refined the original diagnosis of 16 patients. A high concordance of single-nucleotide polymorphisms (99.9%) and small insertions and deletions (93.2%) were observed when comparing the results from TGP and whole-exome sequencing of four patients. We tested an in-house STR detection algorithm, and it reached a specificity of 0.88 and a sensitivity of 0.82 in our SCA3 cohort. This study also uncovered a trove of novel and recurrent variants that may enrich the repertoire of ND-related genetic markers. We propose that a combination of comprehensive TGPs and the bioinformatics analysis pipeline can improve the clinical diagnosis and accelerate the diagnosis of NDs.","abstract":"Genetic testing for diagnosis of neurodegenerative diseases (NDs) is highly challenging because of genotype heterogeneity and overlapping clinical manifestations. Targeted-gene panels (TGPs), coupled with next-generation sequencing (NGS), can facilitate the profiling of a large repertoire of ND-related genes and help with differential diagnosis. Due to the technical limitations inherent in NGS and TGPs, short tandem repeat (STR) variations are often ignored. However, STR expansions are known to cause such NDs as Huntington’s disease and several types of spinocerebellar ataxias, such as SCA type 3 (SCA3).Here, we studied the clinical utility of a custom-made TGP that targets 199 NDs and 311 ND-associated genes on 118 undiagnosed patients. At least one known pathogenic or likely pathogenic variation was found in 54 (45.8%) patients; 27 (22.9%) of the 118 patients demonstrated clinical profiles that matched the variants. Based on the findings from the TGP, we refined the original diagnosis of 16 patients. A high concordance of single-nucleotide polymorphisms (99.9%) and small insertions and deletions (93.2%) were observed when comparing the results from TGP and whole-exome sequencing of four patients. We tested an in-house STR detection algorithm, and it reached a specificity of 0.88 and a sensitivity of 0.82 in our SCA3 cohort. This study also uncovered a trove of novel and recurrent variants that may enrich the repertoire of ND-related genetic markers. We propose that a combination of comprehensive TGPs and the bioinformatics analysis pipeline can improve the clinical diagnosis and accelerate the diagnosis of NDs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-28T09:36:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003738","title":"RNA-seq from human embryonic tissues (additional samples 2018)","description":"How the genome activates or silences transcriptional programmes governs organ formation. Little is known about this in human post-implantation embryos undermining our ability to benchmark the fidelity of in vitro stem cell differentiation or cell programming, or interpret noncoding variation as potential causes of disease. Here, by studying histone modification we identified genome-wide open chromatin states and active repression across thirteen tissues during human organogenesis. We integrated the data with transcription to build the first view of how promoter states from nearly 20,000 genes differentially regulate alternative organ fates, arguing against bivalency during human organogenesis. The data illustrate tissue-specific as well as complex patterns of enhancer activity functional in zebrafish and impute master transcription factors. Overlaying 739 noncoding de novo mutations in patients allowed phenotypic correlation of developmental disorders to unanticipated target genes. Taken together, the data provide a comprehensive genomic framework for understanding normal and abnormal human development.","abstract":"How the genome activates or silences transcriptional programmes governs organ formation. Little is known about this in human post-implantation embryos undermining our ability to benchmark the fidelity of in vitro stem cell differentiation or cell programming, or interpret noncoding variation as potential causes of disease. Here, by studying histone modification we identified genome-wide open chromatin states and active repression across thirteen tissues during human organogenesis. We integrated the data with transcription to build the first view of how promoter states from nearly 20,000 genes differentially regulate alternative organ fates, arguing against bivalency during human organogenesis. The data illustrate tissue-specific as well as complex patterns of enhancer activity functional in zebrafish and impute master transcription factors. Overlaying 739 noncoding de novo mutations in patients allowed phenotypic correlation of developmental disorders to unanticipated target genes. Taken together, the data provide a comprehensive genomic framework for understanding normal and abnormal human development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-28T11:12:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003739","title":"DNA methylation in bronchial biopsies of asthmatics, asthma in remission and healthy subjects","description":"The study focus was differential methylation in bronchial biopsies between persistent asthma, asthma in remission and healthy controls using Illumina 450k arrays.","abstract":"The study focus was differential methylation in bronchial biopsies between persistent asthma, asthma in remission and healthy controls using Illumina 450k arrays.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-28T11:43:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003740","title":"Genomics_of_acral_lentiginous_melanoma","description":"Melanoma is the most aggressive type of skin cancer, causing about 75% of dermatological cancer deaths. Acral lentiginous melanoma (ALM) is the most common subtype of melanoma in admixed Latin American populations, but very few tumour genomes and exomes, all from European-descent individuals, have been analysed across several studies. Because of this, the genomic landscape of ALM is mostly unknown. Our aim in this project is to define this landscape and identify driver somatic alterations by whole-exome sequencing a collection of ALM germline/tumour paired FFPE samples from the National Cancer Institute of Mexico.","abstract":"Melanoma is the most aggressive type of skin cancer, causing about 75% of dermatological cancer deaths. Acral lentiginous melanoma (ALM) is the most common subtype of melanoma in admixed Latin American populations, but very few tumour genomes and exomes, all from European-descent individuals, have been analysed across several studies. Because of this, the genomic landscape of ALM is mostly unknown. Our aim in this project is to define this landscape and identify driver somatic alterations by whole-exome sequencing a collection of ALM germline/tumour paired FFPE samples from the National Cancer Institute of Mexico.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-06-28T11:46:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003741","title":"EMC-DC-IL10R study: RNASeq analysis of moDC and PBMC from healthy human donors and pediatric IBD patients","description":"Uncontrolled interferon gamma (IFNg)-mediated T-cell responses to commensal microbiota are a driver of inflammatory bowel disease (IBD). Interleukin-10 (IL-10) is crucial for controlling these T-cell responses, but the precise mechanism of inhibition remains unclear. Using monocyte derived dendritic cells from a patient with an IL10RA deficiency or moDC and PBMC from patients with severe Pediatric Inflammatory Bowel disease we demonstrate that IL-10 signaling in moDCs, but not T cells, is essential for controlling IFNg-secreting CD4+ T cells.","abstract":"Uncontrolled interferon gamma (IFNg)-mediated T-cell responses to commensal microbiota are a driver of inflammatory bowel disease (IBD). Interleukin-10 (IL-10) is crucial for controlling these T-cell responses, but the precise mechanism of inhibition remains unclear. Using monocyte derived dendritic cells from a patient with an IL10RA deficiency or moDC and PBMC from patients with severe Pediatric Inflammatory Bowel disease we demonstrate that IL-10 signaling in moDCs, but not T cells, is essential for controlling IFNg-secreting CD4+ T cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003742","title":"First Whole Genomes sequences from the UAE","description":null,"abstract":"In this study, for the first time, whole genome sequences of two nationals of the United Arab Emirates (UAE) at &gt;27X coverage are reported. The two Emirati individuals were predominantly of Central/South Asian ancestry.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003743","title":"HSC_population_dynamics___CB002_samples","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-01T15:33:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003744","title":"Single_cell_HSC_colony_WGS_many_years_post_allogeneic_bone_marrow_transplant","description":"This study looks at human donors and recipients of allogeneic blood &amp; marrow marrow transplantation. Each transplant \"pair\" (donor &amp; recipient) underwent the transplant procedure 10 -30 years prior to sampling - the majority for an underlying diagnosis of leukemia.  We will perform whole-genome sequencing on tens to hundreds of single HSPC (haematopoietic stem and progenitor cell)-derived colonies per individual. We will infer the phylogeny of these cells (those from both donor &amp; recipient within a pair) by analysing the somatically acquired mutations within each cell. The structure of the phylogeny will allow estimates of hitherto unknown parameters such as the number of HSCs that engraft long-term, the dynamics of the engraftment process on the HSC level, and the additional mutation burden acquired through the arduous transplant procedure.","abstract":"We propose the use of whole genome sequencing, along with state-of-the-art phylogenetic methods, to reconstruct the dynamics of stem cell engraftment in patients undergoing allogeneic stem cell transplantation for haematological disease:\n\t\n-\tHow many infused haematopoietic stem cells successfully engraft and contribute to subsequent haematopoiesis in human recipients?\n-\tWhat is the time course and phylogenetic structure of stem cell reconstitution?\n-\tAre the outputs of individual engrafting stem_cells biased towards particular lineages e.g. myeloid vs B/T lymphoid?\n\nWithin our study cohort we anticipate a variety of recipient/ donor characteristics, conditioning regimens (myeloablative or reduced-intensity) and other transplant variables (e.g. transplanted cell dose).  Although this study will not have statistical power to draw definitive conclusions on how these differences affect transplant phylodynamics it will establish proof of principle for this type of analysis and inform hypotheses for future studies.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-01T13:33:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003745","title":"Reference exome data for Australian Aboriginal populations to support health-based research","description":"Whole exome sequencing (WES) is a popular and successful technology which is widely used in both research and clinical settings.  However, there is a paucity of reference data for Aboriginal Australians to underpin the translation of health-based genomic research.  Here we provide a catalogue of variants called after sequencing the exomes of 50 Aboriginal individuals from the Northern Territory (NT) of Australia and compare these to 72 previously published exomes from a Western Australian (WA) population of Martu origin.  Sequence data for both NT and WA samples were processed using an ‘intersect-then-combine’ (ITC) approach, using GATK and SAMtools to call variants.   A total of 289,829 variants were identified in at least one individual in the NT cohort and 248,374 variants in at least one individual in the WA cohort.  Of these, 166,719 variants were present in both cohorts, whilst 123,110 variants were private to the NT cohort and 81,655 were private to the WA cohort.  Our data set provides a useful reference point for genomic studies on Aboriginal Australians.","abstract":"Whole exome sequencing (WES) is a popular and successful technology which is widely used in both research and clinical settings.  However, there is a paucity of reference data for Aboriginal Australians to underpin the translation of health-based genomic research.  Here we provide a catalogue of variants called after sequencing the exomes of 50 Aboriginal individuals from the Northern Territory (NT) of Australia and compare these to 72 previously published exomes from a Western Australian (WA) population of Martu origin.  Sequence data for both NT and WA samples were processed using an ‘intersect-then-combine’ (ITC) approach, using GATK and SAMtools to call variants.   A total of 289,829 variants were identified in at least one individual in the NT cohort and 248,374 variants in at least one individual in the WA cohort.  Of these, 166,719 variants were present in both cohorts, whilst 123,110 variants were private to the NT cohort and 81,655 were private to the WA cohort.  Our data set provides a useful reference point for genomic studies on Aboriginal Australians.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-02T07:26:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003746","title":"Integrative genomic analysis identifies key pathogenic mechanisms in primary mediastinal large B-cell lymphoma","description":"Primary mediastinal large B-cell lymphoma (PMBL) represents a clinically and pathologically distinct subtype of large B-cell lymphomas. Furthermore, molecular studies, including global gene expression profiling, have provided evidence that PMBL is more closely related to classical Hodgkin lymphoma (cHL). Although targeted sequencing studies have revealed a number of mutations involved in PMBL pathogenesis, a comprehensive description of disease-associated genetic alterations and perturbed pathways is still lacking.  Here, we performed whole-exome sequencing of 95 PMBL tumors to inform on oncogenic driver genes and recurrent copy number alterations. The integration of somatic gene mutations with gene expression signatures provides further insights into genotype-phenotype interrelation in PMBL.  We identified highly recurrent oncogenic mutations in the JAK-STAT and NF-kB pathways, and provide additional evidence of the importance of immune evasion in PMBL (CIITA, CD58, B2M, CD274, PDCD1LG2). Our analyses highlight the IRF-pathway as a putative novel hallmark with frequent alterations in multiple pathway members (IRF2BP2, IRF4, IRF8). In addition, our integrative analysis illustrates the importance of JAK1, RELB and EP300 mutations driving oncogenic signaling.  The identified driver genes were significantly more frequently mutated in PMBL as compared to diffuse large B-cell lymphoma, whereas only a limited number of genes were significantly different between PMBL and cHL, emphasizing the close relationship between these entities. Our study, performed on a large cohort of PMBL, highlights the importance of distinctive genetic alterations for disease taxonomy with relevance for diagnostic work-up and therapeutic decision-making.","abstract":"Primary mediastinal large B-cell lymphoma (PMBL) represents a clinically and pathologically distinct subtype of large B-cell lymphomas. Furthermore, molecular studies, including global gene expression profiling, have provided evidence that PMBL is more closely related to classical Hodgkin lymphoma (cHL). Although targeted sequencing studies have revealed a number of mutations involved in PMBL pathogenesis, a comprehensive description of disease-associated genetic alterations and perturbed pathways is still lacking.  Here, we performed whole-exome sequencing of 95 PMBL tumors to inform on oncogenic driver genes and recurrent copy number alterations. The integration of somatic gene mutations with gene expression signatures provides further insights into genotype-phenotype interrelation in PMBL.  We identified highly recurrent oncogenic mutations in the JAK-STAT and NF-kB pathways, and provide additional evidence of the importance of immune evasion in PMBL (CIITA, CD58, B2M, CD274, PDCD1LG2). Our analyses highlight the IRF-pathway as a putative novel hallmark with frequent alterations in multiple pathway members (IRF2BP2, IRF4, IRF8). In addition, our integrative analysis illustrates the importance of JAK1, RELB and EP300 mutations driving oncogenic signaling.  The identified driver genes were significantly more frequently mutated in PMBL as compared to diffuse large B-cell lymphoma, whereas only a limited number of genes were significantly different between PMBL and cHL, emphasizing the close relationship between these entities. Our study, performed on a large cohort of PMBL, highlights the importance of distinctive genetic alterations for disease taxonomy with relevance for diagnostic work-up and therapeutic decision-making.","study_type":"Other","pubmed_ids":[31292115],"external_links":null,"is_released":true,"released_date":"2019-07-02T23:44:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003747","title":"Gene expression profile of mesothelial-derived carcinoma-associated fibroblasts","description":"RNA-sequencing was carried out on ascetic fluid-isolated mesothelial cells from low-grade serous ovarian cancer patients, high-grade serous ovarian cancer patients, chemotherapy-treated high-grade serous ovarian cancer patients and control mesothelial cells obtained from non-oncologic patients to identify differentially expressed genes associated to mesothelial-to-mesenchymal transition process.","abstract":"RNA-sequencing was carried out on ascetic fluid-isolated mesothelial cells from low-grade serous ovarian cancer patients, high-grade serous ovarian cancer patients, chemotherapy-treated high-grade serous ovarian cancer patients and control mesothelial cells obtained from non-oncologic patients to identify differentially expressed genes associated to mesothelial-to-mesenchymal transition process.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-03T09:46:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003748","title":"COMPARE study: participants typed during UK Biobank version 2 array development phase","description":"The COMPARE study enrolled 29,066 British blood between donors between February 2016 and March 2017, the study aim is to find the optimum technology for haemoglobin screening (ISRCTN 90871183). All participants were at the time of recruitment active blood donors. The 4,796 participants in this dataset have consented to join the NIHR BioResource. Genotyping data was produced using the Thermo Fisher Scientific Axiom Genotyping platform. The UK Biobank version 2 array design was used, content on this array has been added to allow for accurate DNA based identification of human blood group antigens.","abstract":"The COMPARE study enrolled 29,066 British blood between donors between February 2016 and March 2017, the study aim is to find the optimum technology for haemoglobin screening (ISRCTN 90871183). All participants were at the time of recruitment active blood donors. The 4,796 participants in this dataset have consented to join the NIHR BioResource. Genotyping data was produced using the Thermo Fisher Scientific Axiom Genotyping platform. The UK Biobank version 2 array design was used, content on this array has been added to allow for accurate DNA based identification of human blood group antigens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-03T11:53:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003749","title":"Multi-layered molecular characterization defines prognostic subtypes of lung adenocarcinoma in Asian never-smokers","description":null,"abstract":"Multi-layered genomic studies such as the TCGA project have greatly advanced our understanding on molecular pathogenesis of lung cancer. For Asian nonsmoker patients, however, majority of studies have been limited to mutational analyses, emphasizing ethnic differences in driver mutations (e.g. more frequent EGFR mutations and ALK fusions). In essence, a comprehensive multi-layered characterization that could lead to molecular etiology and patient stratification scheme to be translated into clinical applications for this patient group is still missing. Here we report molecular profiling of tumor and matched normal tissues from 114 non-small-cell lung adenocarcinoma patients using whole exome sequencing, transcriptome sequencing, and array comparative genomic hybridization (CGH).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003750","title":"Glioblastoma initiating cells are sensitive to histone demethylase inhibition due to epigenetic deregulation","description":"Tumor-initiating cells are a subpopulation of cells that have self-renewal capacity to regenerate a tumor. Here, we identify stem cell-like chromatin features in human glioblastoma initiating cells (GICs) and link them to a loss of the repressive histone H3 lysine 9 trimethylation (H3K9me3) mark. Increasing H3K9me3 levels by histone demethylase inhibition led to cell death in GICs but not in their differentiated counterparts. The induction of apoptosis was accompanied by a loss of the activating H3 lysine 9 acetylation (H3K9ac) modification and accumulation of DNA damage and downregulation of DDR genes. Upon knockdown of histone demethylases KDM4C and KDM7A both differentiation and DNA damage was induced. Thus, the H3K9me3-H3K9ac equilibrium is crucial for GIC viability and represents a chromatin feature that can be exploited to specifically target this tumor subpopulation.","abstract":"Tumor-initiating cells are a subpopulation of cells that have self-renewal capacity to regenerate a tumor. Here, we identify stem cell-like chromatin features in human glioblastoma initiating cells (GICs) and link them to a loss of the repressive histone H3 lysine 9 trimethylation (H3K9me3) mark. Increasing H3K9me3 levels by histone demethylase inhibition led to cell death in GICs but not in their differentiated counterparts. The induction of apoptosis was accompanied by a loss of the activating H3 lysine 9 acetylation (H3K9ac) modification and accumulation of DNA damage and downregulation of DDR genes. Upon knockdown of histone demethylases KDM4C and KDM7A both differentiation and DNA damage was induced. Thus, the H3K9me3-H3K9ac equilibrium is crucial for GIC viability and represents a chromatin feature that can be exploited to specifically target this tumor subpopulation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-05T08:47:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003751","title":"Single cell transcriptomic analysis of the immune cell compartment in the human small intestine and in Celiac disease","description":"Celiac disease is an autoimmune disorder in which ingestion of dietary gluten triggers an immune reaction in the small intestine leading to destruction of the lining epithelium. Current treatment focusses on lifelong adherence to a gluten-free diet. Gluten-specific CD4+ T cells and cytotoxic intraepithelial CD8+ T cells have been proposed to be central in disease pathogenesis. Here we use unbiased single-cell RNA-sequencing and explore the heterogeneity of CD45+ immune cells in the human small intestine. We show altered myeloid cell transcriptomes present in active celiac lesions. CD4+ and CD8+ T cells transcriptomes show extensive changes and we define a natural intraepithelial lymphocyte population that is reduced in celiac disease. We show that the immune landscape in Celiac patients on a gluten-free diet is only partially restored compared to control samples. Altogether, we provide a single cell transcriptome resource that can inform the immune landscape of the small intestine during Celiac disease.","abstract":"Celiac disease is an autoimmune disorder in which ingestion of dietary gluten triggers an immune reaction in the small intestine leading to destruction of the lining epithelium. Current treatment focusses on lifelong adherence to a gluten-free diet. Gluten-specific CD4+ T cells and cytotoxic intraepithelial CD8+ T cells have been proposed to be central in disease pathogenesis. Here we use unbiased single-cell RNA-sequencing and explore the heterogeneity of CD45+ immune cells in the human small intestine. We show altered myeloid cell transcriptomes present in active celiac lesions. CD4+ and CD8+ T cells transcriptomes show extensive changes and we define a natural intraepithelial lymphocyte population that is reduced in celiac disease. We show that the immune landscape in Celiac patients on a gluten-free diet is only partially restored compared to control samples. Altogether, we provide a single cell transcriptome resource that can inform the immune landscape of the small intestine during Celiac disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-05T09:38:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003752","title":"Both rare and common genetic variants contribute to autism in the Faroe Islands","description":null,"abstract":"The goal of our study was to better understand the genetic architecture of autism in isolated populations by highlighting the role of both common and rare gene variants. Data from SNP array and whole exome sequencing revealed that individuals with autism had a higher burden of rare exonic copy-number variants altering autism associated genes, higher inbreeding status and a higher load of rare homozygous deleterious variants compared to controls. Our analysis supports the role of several genes/loci associated with autism, identified new truncating or recessive deleterious variants affecting autism-associated genes and pointed at new autism-risk genes involved in synaptic plasticity.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003753","title":"Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses","description":"Background Single-cell RNA sequencing (scRNAseq) is a powerful tool for studying complex biological systems, such as tumour heterogeneity and tissue microenvironments. However, the sources of technical and biological variation in primary solid tumour tissues and patient-derived mouse xenografts for scRNAseq, are not well understood. Here, we used low temperature (6°C) protease and collagenase (37°C) to identify the transcriptional signatures associated with tissue dissociation across a diverse scRNAseq dataset comprising 128,481 cells from patient cancer tissues, patient-derived breast cancer xenografts and cancer cell lines.Results We observe substantial variation in standard quality control (QC) metrics of cell viability across conditions and tissues. From FACS sorted populations gated for cell viability, we identify a sub-population of dead cells that would pass standard data filtering practices, and quantify the extent to which their transcriptomes differ from live cells. We identify a further subpopulation of transcriptomically “dying” cells that exhibit up-regulation of MHC class I transcripts, in contrast with live and fully dead cells. From the contrast between tissue protease dissociation at 37°C or 6°C, we observe that collagenase digestion results in a stress response. We derive a core gene set of 512 heat shock and stress response genes, including FOS and JUN, induced by collagenase (37°C), which are minimized by dissociation with a cold active protease (6°C). While induction of these genes was highly conserved across all cell types, cell type-specific responses to collagenase digestion were observed in patient tissues. We observe that the yield of cancer and non-cancer cell types varies between tissues and dissociation methods.Conclusions The method and conditions of tumour dissociation influence cell yield and transcriptome state and are both tissue and cell type dependent. Interpretation of stress pathway expression differences in cancer single cell studies, including components of surface immune recognition such as MHC class I, may be especially confounded. We define a core set of 512 genes that can assist with identification of such effects in dissociated scRNA-seq experiments.","abstract":"Background Single-cell RNA sequencing (scRNAseq) is a powerful tool for studying complex biological systems, such as tumour heterogeneity and tissue microenvironments. However, the sources of technical and biological variation in primary solid tumour tissues and patient-derived mouse xenografts for scRNAseq, are not well understood. Here, we used low temperature (6°C) protease and collagenase (37°C) to identify the transcriptional signatures associated with tissue dissociation across a diverse scRNAseq dataset comprising 128,481 cells from patient cancer tissues, patient-derived breast cancer xenografts and cancer cell lines.Results We observe substantial variation in standard quality control (QC) metrics of cell viability across conditions and tissues. From FACS sorted populations gated for cell viability, we identify a sub-population of dead cells that would pass standard data filtering practices, and quantify the extent to which their transcriptomes differ from live cells. We identify a further subpopulation of transcriptomically “dying” cells that exhibit up-regulation of MHC class I transcripts, in contrast with live and fully dead cells. From the contrast between tissue protease dissociation at 37°C or 6°C, we observe that collagenase digestion results in a stress response. We derive a core gene set of 512 heat shock and stress response genes, including FOS and JUN, induced by collagenase (37°C), which are minimized by dissociation with a cold active protease (6°C). While induction of these genes was highly conserved across all cell types, cell type-specific responses to collagenase digestion were observed in patient tissues. We observe that the yield of cancer and non-cancer cell types varies between tissues and dissociation methods.Conclusions The method and conditions of tumour dissociation influence cell yield and transcriptome state and are both tissue and cell type dependent. Interpretation of stress pathway expression differences in cancer single cell studies, including components of surface immune recognition such as MHC class I, may be especially confounded. We define a core set of 512 genes that can assist with identification of such effects in dissociated scRNA-seq experiments.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-08T18:40:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003754","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___POL___TGS_","description":"Somatic mutations (burdens and signatures) and clonal dynamics in individuals with germline DNA polymerase mutations.","abstract":"The aim of this project is to investigate somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the study of normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to identify and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-09T13:20:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003755","title":"High intensity sequencing of plasma cfDNA and WBC gDNA","description":"We sought to define the technical feasibility of a high-intensity sequencing assay of cfDNA and matched white-blood cell (WBC) DNA covering a large genomic region (508 genes, 2Mb, 60,000x raw-depth) in a prospective study of 124 metastatic cancer patients, with contemporaneous matched metastatic tumor tissue biopsies, and age-matched 47 non-cancer controls.","abstract":"We sought to define the technical feasibility of a high-intensity sequencing assay of cfDNA and matched white-blood cell (WBC) DNA covering a large genomic region (508 genes, 2Mb, 60,000x raw-depth) in a prospective study of 124 metastatic cancer patients, with contemporaneous matched metastatic tumor tissue biopsies, and age-matched 47 non-cancer controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-10T08:55:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003756","title":"RNA-seq of cultured human hematopoietic stem and progenitor cells from umblical cord blood in cytokine-rich ex vivo culture conditions following sphingolipid modulation","description":"To elucidate the biological pathways altered by sphingolipid modulation with N-(4-hydroxyphenyl) retinamide (4HPR) treatment in human HSPC that may contribute to the restraint in proliferation while promoting persistence of HSC self-renewal as well as determine the mechanism of synergy in enhancement of HSC self-renewal with CB CD34+ agonists UM171 and StemRegenin 1 (SR1), we performed RNA-sequencing (RNA-Seq) of 3 pools of lin-CB cells following 2 or 4 days with DMSO, 4HPR, UM171+SR1 or 3-Factor (4HPR+UM171+SR1). We identified modulation of sphingolipid metabolism regulates self-renewal through activating coordinated stress pathways that coalesce on endoplasmic reticulum stress and autophagy programs.","abstract":"To elucidate the biological pathways altered by sphingolipid modulation with N-(4-hydroxyphenyl) retinamide (4HPR) treatment in human HSPC that may contribute to the restraint in proliferation while promoting persistence of HSC self-renewal as well as determine the mechanism of synergy in enhancement of HSC self-renewal with CB CD34+ agonists UM171 and StemRegenin 1 (SR1), we performed RNA-sequencing (RNA-Seq) of 3 pools of lin-CB cells following 2 or 4 days with DMSO, 4HPR, UM171+SR1 or 3-Factor (4HPR+UM171+SR1). We identified modulation of sphingolipid metabolism regulates self-renewal through activating coordinated stress pathways that coalesce on endoplasmic reticulum stress and autophagy programs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-10T19:16:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003757","title":"_Lung_Cell_Atlas_HCA_MRC","description":"scRNA-Seq for for fetal lung , plus single cell ATACseq for adult and fetal lung \n\nThe aim of this study is to assess single cell gene expression profiles across the developing human lung. In addition to this, we will carry out ATACseq of both fetal lung samples and adult lung samples to better understand regulatory networks and developmental trajectories in the human lung.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"scRNA-Seq for for fetal lung , plus single cell ATACseq for adult and fetal lung \n\nThe aim of this study is to assess single cell gene expression profiles across the developing human lung. In addition to this, we will carry out ATACseq of both fetal lung samples and adult lung samples to better understand regulatory networks and developmental trajectories in the human lung.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003758","title":"Genomics_of_acral_lentiginous_melanoma___RNAseq","description":"Melanoma is the most aggressive type of skin cancer, causing about 75% of dermatological cancer deaths. Acral lentiginous melanoma (ALM) is the most common subtype of melanoma in admixed Latin American populations, but very few tumour genomes and exomes, all from European-descent individuals, have been analysed across several studies. Because of this, the genomic landscape of ALM is mostly unknown. Our aim in this project is to define this landscape and identify driver somatic alterations by whole-exome sequencing a collection of ALM germline/tumour paired FFPE samples from the National Cancer Institute of Mexico.","abstract":"Melanoma is the most aggressive type of skin cancer, causing about 75% of dermatological cancer deaths. Acral lentiginous melanoma (ALM) is the most common subtype of melanoma in admixed Latin American populations, but very few tumour genomes and exomes, all from European-descent individuals, have been analysed across several studies. Because of this, the genomic landscape of ALM is mostly unknown. Our aim in this project is to define this landscape and identify driver somatic alterations by whole-exome sequencing a collection of ALM germline/tumour paired FFPE samples from the National Cancer Institute of Mexico.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-12T12:37:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003759","title":"Accurate detection of circulating tumor DNA using nanopore consensus sequencing","description":"Levels of circulating tumor DNA (ctDNA) in liquid biopsies may serve as a sensitive biomarker for real-time, minimally-invasive tumor diagnostics and monitoring. However, detecting ctDNA is challenging, as much fewer than 5% of the cell-free DNA in the blood typically originates from the tumor. To detect lowly abundant ctDNA molecules based on somatic variants, extremely sensitive sequencing methods are required. Here, we describe a new technique, CyclomicsSeq, which is based on Oxford Nanopore sequencing of concatenated copies of a single DNA molecule. Consensus calling of the DNA copies increased the base-calling accuracy ~60×, enabling accurate detection of TP53 mutations at frequencies down to 0.02%. We demonstrate that a TP53-specific CyclomicsSeq assay can be successfully used to monitor tumor burden during treatment for head-and-neck cancer patients. CyclomicsSeq can be applied to any genomic locus and offers an accurate diagnostic liquid biopsy approach that can be implemented in clinical workflows.","abstract":"Levels of circulating tumor DNA (ctDNA) in liquid biopsies may serve as a sensitive biomarker for real-time, minimally-invasive tumor diagnostics and monitoring. However, detecting ctDNA is challenging, as much fewer than 5% of the cell-free DNA in the blood typically originates from the tumor. To detect lowly abundant ctDNA molecules based on somatic variants, extremely sensitive sequencing methods are required. Here, we describe a new technique, CyclomicsSeq, which is based on Oxford Nanopore sequencing of concatenated copies of a single DNA molecule. Consensus calling of the DNA copies increased the base-calling accuracy ~60×, enabling accurate detection of TP53 mutations at frequencies down to 0.02%. We demonstrate that a TP53-specific CyclomicsSeq assay can be successfully used to monitor tumor burden during treatment for head-and-neck cancer patients. CyclomicsSeq can be applied to any genomic locus and offers an accurate diagnostic liquid biopsy approach that can be implemented in clinical workflows.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003760","title":"Genetics and transcriptomes of pediatric B cell precursor leukemia with gain of chromosome 21","description":"Down syndrome (DS, constitutive trisomy 21) children have a 27-fold increased risk of developing B-ALL (DS-ALL), face a worse outcome due to treatment-related morbidities, and an increased rate of relapses compared to other children. This highlights the need to better understand the mechanisms of DS-associated leukemogenesis to develop more adapted treatment. In this study, we characterized the genetic and transcriptomic landscapes of DS-ALL and found a high incidence of somatic mutations leading to RAS/MAPK pathway activation in DS-ALL, as seen in other pediatric B-ALL presenting somatic gains of the chromosome 21 (B-ALL+21).","abstract":"Down syndrome (DS, constitutive trisomy 21) children have a 27-fold increased risk of developing B-ALL (DS-ALL), face a worse outcome due to treatment-related morbidities, and an increased rate of relapses compared to other children. This highlights the need to better understand the mechanisms of DS-associated leukemogenesis to develop more adapted treatment. In this study, we characterized the genetic and transcriptomic landscapes of DS-ALL and found a high incidence of somatic mutations leading to RAS/MAPK pathway activation in DS-ALL, as seen in other pediatric B-ALL presenting somatic gains of the chromosome 21 (B-ALL+21).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-12T16:17:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003761","title":"Low_input_WGS_paired_with_WGMS","description":"Development of a whole-genome sequence and whole-genome methylation seq pipeline that provides both libraries from a single low input (sub 10ng) sample as used in the low input LCM pipelines.","abstract":"Development of a whole-genome sequence and whole-genome methylation seq pipeline that provides both libraries from a single low input (sub 10ng) sample as used in the low input LCM pipelines.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003762","title":"Low_Input_WGMS","description":"Development of a whole-genome methylation seq pipeline that provides &gt;80% genome coverage using low quantities of DNA (&lt;10ng) as input using a novel enzymatic method to assess DNA methylation.","abstract":"Development of a whole-genome methylation seq pipeline that provides &gt;80% genome coverage using low quantities of DNA (&lt;10ng) as input using a novel enzymatic method to assess DNA methylation.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003763","title":"Landscape and significance of multiple mutations in oncogenes.","description":"This study is a comprehensive pan-cancer study of oncogenic multiple mutations (MMs) which includes long-read whole-genome sequencing data (n = 3).","abstract":"This study is a comprehensive pan-cancer study of oncogenic multiple mutations (MMs) which includes long-read whole-genome sequencing data (n = 3).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-16T03:52:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003764","title":"WES of mCRC xenografts under cetuximab treatment, placebo or after treatment release","description":"Determine if cetuximab treatment selects any pre-existing resistant subclones or if the resistant cells, which in vivo determines residual disease, are driven by plasticity effects not linked to mutations.","abstract":"Determine if cetuximab treatment selects any pre-existing resistant subclones or if the resistant cells, which in vivo determines residual disease, are driven by plasticity effects not linked to mutations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-17T16:17:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003765","title":"RNAseq of mCRC xenografts under cetuximab treatment, placebo or after treatment release","description":"Determine if cetuximab treatment selects any pre-existing resistant subclones or if the resistant cells, which in vivo determines residual disease, are driven by plasticity effects not linked to mutations.","abstract":"Determine if cetuximab treatment selects any pre-existing resistant subclones or if the resistant cells, which in vivo determines residual disease, are driven by plasticity effects not linked to mutations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-17T16:17:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003766","title":"Diverse_outcomes_of_controlled_human_malaria_infection_originate_from_host_intrinsic_immune_variation_and_not_var_gene_switching","description":"Falciparum malaria is clinically heterogeneous and the relative contribution of parasite and host factors in shaping disease severity remains unclear. We set out to explore the interaction between host inflammation and parasite variant surface antigen (VSA) expression, asking whether this relationship underpins the variation observed in controlled human malaria infection. We uncovered marked heterogeneity in the response of naive hosts to blood challenge with some volunteers maintaining a state of immune quiescence, others triggering interferon-stimulated inflammation and a small group showing transcriptional evidence of myeloid cell suppression. Significantly, only inflammatory volunteers experienced hallmark symptoms of clinical malaria. When we then tracked temporal changes in parasite VSA expression to ask whether variants associated with severe disease preferentially expand in naive hosts (as predicted by current theory) we found that var gene profiles were essentially unchanged after 10-days of blood-stage infection. These data therefore show that the diverse clinical outcomes of CHMI largely originate from host-intrinsic variation and there is no evidence for switching or selection of var genes in naïve hosts. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Diverse outcomes of controlled human malaria infection originate from host-intrinsic immune variation and not var gene switching","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-17T17:10:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003767","title":"IBD-dysplasia","description":null,"abstract":"Background. \nPatients with longstanding inflammatory bowel disease (IBD, i.e. ulcerative colitis and Crohn’s disease) have an increased risk of colorectal cancer (CRC). Due to the ongoing inflammation, IBD-associated dysplastic lesions can develop. These lesions have an increased risk to progress to cancer compared to the sporadic adenomas that can also be found in these patients. Differentiating between these two types of dysplasia remains challenging, both clinically and histologically, while treatment strategies may differ. Therefore, the aim of this study was to investigate molecular alterations associated with colorectal dysplasia to cancer progression in IBD and evaluate to what extent these alterations differ from sporadic adenomas. \n\nMethods. \nDNA copy number aberrations and mutation analyses of 48 genes were performed by next-generation sequencing in 43 IBD-associated dysplastic lesions, 30 of which were dysplastic and 13 were cancers. Results were compared to existing DNA copy number and mutation data from 118 sporadic adenomas and 24 sporadic cancers. \n\nResults\nIBD-associated dysplastic lesions harbour patterns of DNA copy number aberrations comparable to carcinomas, which are rare in sporadic adenomas. TP53 mutation was the most frequent mutation observed in IBD-associated dysplastic lesions as well as in cancers. FBXW7 was significantly more often mutated in IBD-associated dysplastic lesions than in sporadic adenomas. \n\nConclusions\nIBD-associated dysplastic lesions show more DNA copy number aberrations than sporadic adenomas. TP53 and FBXW7 mutations appear to be involved in the development of IBD associated dysplastic lesions and cancer. These findings indicate that IBD-associated dysplastic lesions are more genomic instable, possibly reflecting a faster progression towards cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-18T17:00:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003768","title":"HSC_population_dynamics___KX004_samples___WGS","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-19T12:53:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003769","title":"Fresh vs. frozen cell preparations of colorectal cancer single-cell RNA sequencing","description":null,"abstract":"To evaluate 3 different tissue dissociation protocols or fresh vs. frozen cell preparations, we performed single-cell RNA sequencing on cancer or distant normal tissue dissociates from 2 colorectal cancer patients. Total 18,409 cells from 10 sample preparations were analyzed (5 primary colorectal cancer and 5 matched normal mucosa). The results suggest highly consistent cellular proportions were recovered with different sample preparation methods.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-21T08:14:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003770","title":"Mapping_genetic_variants_underlying_gene_regulation_in_inflammed_intestinal_cell_types_to_identify_novel_IBD_drug_targets","description":"Biopsies from the terminal ileum and rectum of individuals with Crohn's disease are digested on ice to single cells and processed for single-cell RNA-sequencing (10X Genomics and Illumina)\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The vast majority of the association signals detected via genome-wide association studies lie in noncoding parts of the genome. Therefore, to identify potential drug targets from within these loci we must first identify the gene dysregulated by the IBD associated allele. To do this we use statistical methods to colocalise our IBD associations with gene expression quantitative trait loci (eQTL). Many of the eQTL maps that are currently available have been generated using peripheral immune cells, but we have found colocalisations for only ~15% of IBD loci, suggesting that eQTL maps of additional disease relevant tissues are needed. Here, we use single-cell sequencing of inflammed terminal ileum biopsies from 160 CD patients to create the ultimate eQTL map for identifying effector genes perturbed by IBD GWAS loci. This map will include eQTL within and across the more than 40 different cell types in the gut (both epithelial and immune cells). By fine-mapping within colocalised eQTLs we will also increase our power to detect causal IBD variants for downstream function work.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-22T11:22:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003771","title":"Exome sequencing in the clinic: a prospective clinical case series","description":null,"abstract":"The cases included here were part of a larger set collected prospectively as part of a clinical exome sequencing project aiming to identify the causes of rare disease across a variety of clinical specialties. \n Cases were triaged through a Genomic Medicine MDT as part of a multi-disciplinary approach to promote engagement, inform decision-making, and support clinicians\nand patients.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003772","title":"The_Genomic_Advances_in_Sepsis__GAinS__RNA_seq","description":"Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. This cohort comprises a subset of patients enrolled in the Genomic Advances in Sepsis (GAinS) study, an established biobank of adult sepsis patients. Patients with sepsis due to community acquired pneumonia or faecal peritonitis were recruited from 34 hospitals across the UK from 2005-2018, with samples for functional genomics and detailed clinical information collected on the first, third and/or fifth day following ICU admission. RNA was extracted from leukocytes isolated at the bedside using LeukoLOCK kits.\nWe have previously identified sepsis response signatures (SRSs), transcriptomic endotypes that are associated with differential early mortality (Davenport et al, Lancet Respir Med, 2016; Burnham et al, AJRCCM, 2017) and response to treatment in a clinical trial (Antcliffe et al, AJRCCM, 2018). We generated RNA sequencing data on 903 samples, including 134 samples repeated from our previously released microarray data. Libraries were prepared using NEB Ultra II Library Prep kits (Illumina) and sequenced on a NovaSeq 6000. Reads were aligned to the reference genome (GRCh38) using STAR and gene counts quantified using featureCounts (annotation Ensembl v99). Counts were TMM-normalised and log-transformed. Following QC, processed data were available on 864 samples from 667 unique patients.","abstract":"Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. This cohort comprises a subset of patients enrolled in the Genomic Advances in Sepsis (GAinS) study, an established biobank of adult sepsis patients. Patients with sepsis due to community acquired pneumonia or faecal peritonitis were recruited from 34 hospitals across the UK from 2005-2018, with samples for functional genomics and detailed clinical information collected on the first, third and/or fifth day following ICU admission. RNA was extracted from leukocytes isolated at the bedside using LeukoLOCK kits.\nWe have previously identified sepsis response signatures (SRSs), transcriptomic endotypes that are associated with differential early mortality (Davenport et al, Lancet Respir Med, 2016; Burnham et al, AJRCCM, 2017) and response to treatment in a clinical trial (Antcliffe et al, AJRCCM, 2018). We generated RNA sequencing data on 903 samples, including 134 samples repeated from our previously released microarray data. Libraries were prepared using NEB Ultra II Library Prep kits (Illumina) and sequenced on a NovaSeq 6000. Reads were aligned to the reference genome (GRCh38) using STAR and gene counts quantified using featureCounts (annotation Ensembl v99). Counts were TMM-normalised and log-transformed. Following QC, processed data were available on 864 samples from 667 unique patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-23T11:09:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003773","title":"Building_a_platform_for_clinical_studies_of_cutaneous_leishmaniasis_in_Ethiopia","description":"In this project, we will recruit a cohort of LCL, MCL and DCL patients in North West Ethiopia. The project aims to identify parasite factors associated with differences in clinical presentation by whole genome sequencing of parasites and identify the immune signatures of host response in specific presentations by in-depth phenotyping of L. aethiopica infections, making use of a non-invasive technique we have previously established, and RNA-seq transcriptomics from blood and skin samples from lesions. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The aim of this project is to develop novel non-invasive approaches to study cutaneous leishmaniasis (CL) in Ethiopia and to build an extended network of collaborators to apply these approaches in clinical studies of this disease","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003774","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__Colorectal","description":"he Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"he Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-25T15:29:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003775","title":"Whole genome and whole transcriptome sequencing of Hepatosplenic T Cell Lymphoma tumor.","description":"Whole genome and whole transcriptome sequencing of Hepatosplenic T Cell Lymphoma tumor.","abstract":"Whole genome and whole transcriptome sequencing of Hepatosplenic T Cell Lymphoma tumor.","study_type":"Other","pubmed_ids":[31988286],"external_links":null,"is_released":true,"released_date":"2019-07-26T04:08:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003776","title":"Targetable ERBB2 Mutations in Neurofibroma/Schwannoma Hybrid Nerve Sheath Tumors","description":null,"abstract":"Neurofibroma/schwannoma hybrid nerve sheath tumors (N/S HNSTs) are neoplasms associated with larger nerves that occur sporadically and in the context of schwannomatosis or neurofibromatosis (NF). Clinical management of N/S HNST is challenging, especially for large tumors, and established systemic treatments are lacking. We identified activating mutations (p.Leu755Ser, p.Asp769Tyr, p.Val777Leu) in the catalytic domain of the ERBB2 receptor tyrosine kinase in schwannomatosis-associated (4 of 8 patients) N/S HNSTs but not in tumors arising in the context of NF (0 of 6 patients), and observed that ERBB2-mutant N/S HNSTs define a distinct subgroup of peripheral nerve sheath tumors based on genome-wide DNA methylation patterns. The small-molecule ERBB inhibitor lapatinib led to prolonged clinical benefit and a lasting radiographic and metabolic response in a patient with schwannomatosis-associated, ERBB2-mutant N/S HNST. These findings uncover a key biological feature of N/S HNST that may have important diagnostic and therapeutic implications. (H021)","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-26T11:29:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003777","title":"Donor InSight III study: Participants typed during UK Biobank version 2 array development phase","description":null,"abstract":"The Donor InSight III study, undertaken by Sanquin research, recruited 3,046 Dutch blood donors between 2015 and 2016. The purpose of the study was to gain more insight into characteristics of donors, their motivations and health. All participants were at the time of recruitment active blood donors. Genotyping data was produced using the Thermo Fisher Scientific Axiom Genotyping platform. The UK Biobank version 2 array design was used, content on this array has been added to allow for accurate DNA based identification of human blood group antigens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003778","title":"The whole genome landscape of Burkitt lymphoma subtypes","description":null,"abstract":"Burkitt lymphoma (BL) is an aggressive, MYC-driven lymphoma comprising three distinct clinical subtypes, including sporadic BLs that occur worldwide, endemic BLs that occur predominantly in sub-Saharan Africa, and immunodeficiency-associated BLs that occur primarily in the setting of HIV. In this study, we comprehensively delineated the genomic basis of BL through whole genome sequencing of 101 tumors representing all 3 subtypes of BL to identify 72 driver genes. These data were additionally informed by CRISPR screens in BL cell lines to functionally annotate the role of oncogenic drivers. Nearly every driver gene was found to have both coding and non-coding mutations highlighting the importance of whole genome sequencing for identifying driver events. Our data implicate coding and non-coding mutations in IGLL5, BACH2, SIN3A and DNMT1. EBV infection was associated with higher mutation load, with EBV type 1 showing a higher mutational burdens than type 2 EBV. While sporadic and immunodeficiency-associated BLs had similar genetic profiles, endemic BLs manifested more frequent mutations in BCL7A and BCL6, and fewer genetic alterations in DNMT1, SNTB2, CTCF. Silencing mutations in ID3 were a common feature of all three subtypes of BL. In vitro, mass spectrometry-based proteomics demonstrated that the ID3 protein binds primarily to TCF3 and TCF4. In vivo knockout of ID3 potentiated the effects of MYC, leading to rapid tumorigenesis and tumor phenotypes consistent with those observed in the human disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-26T21:35:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003779","title":"Single cell RNA sequencing of 33 primary colorectal cancer","description":null,"abstract":"Expression of single-cell mRNA data was obtained from 23 patients with 23 primary colorectal cancer and 10 matched normal mucosa. To remove low-quality cells, we applied filtering criteria using nUMI, nGene and percent of mitochondrial genes and 67,296 cells are passed. To elimination of ambigous cells, we combined the Seurat multiCCA and RCA pipelines for initial clustering and cell type identification and removed discordant cells from 2 methods. After defining major cell types using joint application, cells with a number of genes exceeding the outliers were removed to elimnate doublets and finally 63,689 cells are obtained.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-28T07:31:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003780","title":"Extreme phenotypes define epigenetic and metabolic signatures in cardiovascular diseases.","description":"Improving the understanding of cardiometabolic syndrome pathophysiology and its\nrelationship with thrombosis are ongoing healthcare challenges. Using plasma biomarkers\nanalysis coupled with the transcriptional and epigenetic characterisation of cell types\ninvolved in thrombosis, obtained from two extreme phenotype groups (obese and\nlipodystrophy) and comparing these to lean individuals and blood donors, the present study\nidentifies the molecular mechanisms at play, highlighting patterns of abnormal activation in\ninnate immune phagocytic cells and shows that extreme phenotype groups could be\ndistinguished from lean individuals, and from each other, across all data layers. The\ncharacterisation of the same obese group, six months after bariatric surgery shows the loss of\nthe patterns of abnormal activation of innate immune cells previously observed. However,\nrather than reverting to the gene expression landscape of lean individuals, this occurs via the\nestablishment of novel gene expression landscapes. Netosis and its control mechanisms\nemerge amongst the pathways that show an improvement after surgical intervention. Taken\ntogether, by integrating across data layers, the observed molecular and metabolic differences\nform a disease signature that is able to discriminate, amongst the blood donors, those\nindividuals with a higher likelihood of having cardiometabolic syndrome, even when not\npresenting with the classic features.","abstract":"Improving the understanding of cardiometabolic syndrome pathophysiology and its\nrelationship with thrombosis are ongoing healthcare challenges. Using plasma biomarkers\nanalysis coupled with the transcriptional and epigenetic characterisation of cell types\ninvolved in thrombosis, obtained from two extreme phenotype groups (obese and\nlipodystrophy) and comparing these to lean individuals and blood donors, the present study\nidentifies the molecular mechanisms at play, highlighting patterns of abnormal activation in\ninnate immune phagocytic cells and shows that extreme phenotype groups could be\ndistinguished from lean individuals, and from each other, across all data layers. The\ncharacterisation of the same obese group, six months after bariatric surgery shows the loss of\nthe patterns of abnormal activation of innate immune cells previously observed. However,\nrather than reverting to the gene expression landscape of lean individuals, this occurs via the\nestablishment of novel gene expression landscapes. Netosis and its control mechanisms\nemerge amongst the pathways that show an improvement after surgical intervention. Taken\ntogether, by integrating across data layers, the observed molecular and metabolic differences\nform a disease signature that is able to discriminate, amongst the blood donors, those\nindividuals with a higher likelihood of having cardiometabolic syndrome, even when not\npresenting with the classic features.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-29T16:10:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003781","title":"WXS of 147 lung cancer patients treated with immunotherapy","description":"We first attempted to predict MHC-binding neoantigens at high accuracy with convolutional neural networks. This prediction model outperformed previous methods in &gt; 70% of test cases. Importantly, our method remarkably increased the predictive value of neoantigen load especially in combination with known resistance parameters. We then developed a classifier that can predict resistance from point mutations that are deleterious to protein function. Notably, genes involved in the adaptive immune response, cytokine signaling,and EGFR signaling held high explanatory power. Furthermore, when integrated with our neoantigen profiling, these anti-immunogenic mutations revealed significantly higher predictive power than known resistance factors.","abstract":"We first attempted to predict MHC-binding neoantigens at high accuracy with convolutional neural networks. This prediction model outperformed previous methods in &gt; 70% of test cases. Importantly, our method remarkably increased the predictive value of neoantigen load especially in combination with known resistance parameters. We then developed a classifier that can predict resistance from point mutations that are deleterious to protein function. Notably, genes involved in the adaptive immune response, cytokine signaling,and EGFR signaling held high explanatory power. Furthermore, when integrated with our neoantigen profiling, these anti-immunogenic mutations revealed significantly higher predictive power than known resistance factors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-07-30T09:17:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003782","title":"Inherited Thyroid Cancer Study","description":"Highly penetrant hereditary thyroid cancer manifests as familial nonmedullary thyroid cancer\n(FNMTC), while low-penetrance hereditary thyroid cancer manifests as sporadic disease and is\nassociated with polymorphisms, including rs965513. Whole-exome sequencing of an FNMTC\nkindred identified a novel Y1203H germline Dual Oxidase-2 (DUOX2) mutation. DUOX2Y1203H\nis enzymatically active and increased production of reactive oxygen species. Further analysis\nrevealed that sporadic thyroid cancer patients homozygous for rs965513 demonstrated higher\nDUOX2 expression than heterozygous or homozygous negative patients. These data suggest that\ndysregulated hydrogen peroxide metabolism is a common mechanism by which high- and lowpenetrance\ngenetic factors increase thyroid cancer risk.","abstract":"Highly penetrant hereditary thyroid cancer manifests as familial nonmedullary thyroid cancer\n(FNMTC), while low-penetrance hereditary thyroid cancer manifests as sporadic disease and is\nassociated with polymorphisms, including rs965513. Whole-exome sequencing of an FNMTC\nkindred identified a novel Y1203H germline Dual Oxidase-2 (DUOX2) mutation. DUOX2Y1203H\nis enzymatically active and increased production of reactive oxygen species. Further analysis\nrevealed that sporadic thyroid cancer patients homozygous for rs965513 demonstrated higher\nDUOX2 expression than heterozygous or homozygous negative patients. These data suggest that\ndysregulated hydrogen peroxide metabolism is a common mechanism by which high- and lowpenetrance\ngenetic factors increase thyroid cancer risk.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003783","title":"Molecular characterization of pineoblastoma","description":null,"abstract":"Molecular characterization of pineoblastoma with cases collected through the Rare Brain Tumor Consortium. Tumors were analyzed by global methylation profiling, whole/targeted exome sequencing, and miRNA expression profiling. Five molecular subgroups were found with distinct clinico-pathologic features.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003784","title":"Polyomavirus-positive Merkel cell carcinoma derived from a trichoblastoma suggests an epithelial origin of Merkel cell carcinoma","description":null,"abstract":"To assess the lineage of origin of MCPyV-positive MCC, genetic analysis of a rare tumor combining benign trichoblastoma and MCPyV-positive MCC was conducted by massive parallel sequencing. Although MCPyV was found to be integrated in only the MCC part, six somatic mutations were shared by both tumor components. The mutational overlap between trichoblastoma and MCPyV-positive MCC part of the combined tumor implies that MCPyV integration occurred in an epithelial tumor cell prior to MCC development. Therefore, it appears likely that cells of the epithelial lineage are the origin of MCPyV-positive MCC","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-01T07:32:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003785","title":"Gene expression from human iPSC derived motor neurons.","description":"Gene expression from human iPSC derived motor neurons.","abstract":"Gene expression from human iPSC derived motor neurons.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-01T08:37:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003786","title":"Patient-Derived Lung Cancer Organoid","description":"Lung cancer shows substantial genetic and phenotypic heterogeneity across individuals, driving a need for personalized medicine. Here we report lung cancer organoids and normal bronchial organoids established from patients tissues comprising five histological subtypes of lung cancer and non-neoplastic bronchial mucosa as in vitro models representing individual patient. The lung cancer organoids recapitulate the tissue architecture of the primary lung tumours and maintain the genomic alterations of the original tumours during long-term expansion in vitro. The normal bronchial organoids maintain cellular components of normal bronchial mucosa. Lung cancer organoids respond to drugs based on their genomic alterations: a BRCA2 mutant organoid to olaparib, an EGFR mutant organoid to erlotinib, and an EGFR mutant/MET amplified organoid to crizotinib. Considering the short length of time from organoid establishment to drug testing, our newly developed model may prove useful for predicting patient-specific drug responses through in vitro patient-specific drug trials.","abstract":"Lung cancer shows substantial genetic and phenotypic heterogeneity across individuals, driving a need for personalized medicine. Here we report lung cancer organoids and normal bronchial organoids established from patients tissues comprising five histological subtypes of lung cancer and non-neoplastic bronchial mucosa as in vitro models representing individual patient. The lung cancer organoids recapitulate the tissue architecture of the primary lung tumours and maintain the genomic alterations of the original tumours during long-term expansion in vitro. The normal bronchial organoids maintain cellular components of normal bronchial mucosa. Lung cancer organoids respond to drugs based on their genomic alterations: a BRCA2 mutant organoid to olaparib, an EGFR mutant organoid to erlotinib, and an EGFR mutant/MET amplified organoid to crizotinib. Considering the short length of time from organoid establishment to drug testing, our newly developed model may prove useful for predicting patient-specific drug responses through in vitro patient-specific drug trials.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-01T08:55:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003787","title":"The coding and non-coding transcriptional landscape of subependymal giant cell astrocytomas","description":"Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited neurocutaneous disorder caused by inactivating mutations in TSC1 or TSC2, key regulators of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. In the central nervous system TSC is characterized by cortical tubers, subependymal nodules and subependymal giant cell astrocytomas (SEGAs). SEGAs may lead to the impaired circulation of cerebrospinal fluid resulting in hydrocephalus and raised intracranial pressure in patients with TSC. Currently, surgical resection and mTORC1 inhibitors are the recommended treatment options for patients with SEGA. Here, we performed RNA-Seq and small RNA-Seq on SEGAs (n=19) and periventricular controls (n=8) to gain a better understanding of the underlying molecular basis of SEGAs, so that novel treatment targets could be identified.","abstract":"Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited neurocutaneous disorder caused by inactivating mutations in TSC1 or TSC2, key regulators of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. In the central nervous system TSC is characterized by cortical tubers, subependymal nodules and subependymal giant cell astrocytomas (SEGAs). SEGAs may lead to the impaired circulation of cerebrospinal fluid resulting in hydrocephalus and raised intracranial pressure in patients with TSC. Currently, surgical resection and mTORC1 inhibitors are the recommended treatment options for patients with SEGA. Here, we performed RNA-Seq and small RNA-Seq on SEGAs (n=19) and periventricular controls (n=8) to gain a better understanding of the underlying molecular basis of SEGAs, so that novel treatment targets could be identified.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-01T10:48:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003788","title":"AML_ALL_WGS","description":"Aim of this project is to study human leukemia","abstract":"Aim of this project is to study human leukemia","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003789","title":"'KOREAN' never-smoker female adenocarcinoma RNA-seq","description":"Multi-layered genomic studies such as the TCGA project have greatly advanced our understanding on molecular pathogenesis of lung cancer. For Asian nonsmoker patients, however, majority of studies have been limited to mutational analyses, emphasizing ethnic differences in driver mutations (e.g. more frequent EGFR mutations and ALK fusions). In essence, a comprehensive multi-layered characterization that could lead to molecular etiology and patient stratification scheme to be translated into clinical applications for this patient group is still missing. Here we report molecular profiling of tumor and matched normal tissues from 114 non-small-cell lung adenocarcinoma patients using whole exome sequencing, transcriptome sequencing, and array comparative genomic hybridization (CGH).","abstract":"Multi-layered genomic studies such as the TCGA project have greatly advanced our understanding on molecular pathogenesis of lung cancer. For Asian nonsmoker patients, however, majority of studies have been limited to mutational analyses, emphasizing ethnic differences in driver mutations (e.g. more frequent EGFR mutations and ALK fusions). In essence, a comprehensive multi-layered characterization that could lead to molecular etiology and patient stratification scheme to be translated into clinical applications for this patient group is still missing. Here we report molecular profiling of tumor and matched normal tissues from 114 non-small-cell lung adenocarcinoma patients using whole exome sequencing, transcriptome sequencing, and array comparative genomic hybridization (CGH).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-02T08:36:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003790","title":"Transcriptional changes in GBM through therapy","description":"Primary glioblastoma (GBM) tumours recur following therapy, owing to treatment resistance mechanisms in unresectable cells.  We have sequenced RNA from paired primary and locally recurrent GBM tumours to begin characterising therapy resistant cells and thereby infer the mechanisms by which they evaded treatment. Exome sequencing data from these samples were included in the first data release from the Glioma Longitudinal AnalySiS (GLASS) consortium","abstract":"Primary glioblastoma (GBM) tumours recur following therapy, owing to treatment resistance mechanisms in unresectable cells.  We have sequenced RNA from paired primary and locally recurrent GBM tumours to begin characterising therapy resistant cells and thereby infer the mechanisms by which they evaded treatment. Exome sequencing data from these samples were included in the first data release from the Glioma Longitudinal AnalySiS (GLASS) consortium","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-02T11:10:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003791","title":"Cell-free DNA analysis reveals POLR1D-mediated resistance to bevacizumab in colorectal cancer","description":"Bevacizumab is an approved anti-angiogenic drug for patients with metastasized colorectal cancer (mCRC) targeting VEGF. The survival benefit of anti-VEGF therapy in mCRC patients is limited to a few months and acquired resistance mechanisms are greatly unknown. Using plasma DNA, we studied the evolution of tumor genomes in a cohort of patients with mCRC (n=150) and observed a recurrent focal amplification (8.7% of cases) on chromosome 13q12.2. Analysis of TCGA data (n=619) suggested an association with later stages, which we confirmed by longitudinal plasma analyses. We defined the minimally amplified region and studied the mechanistic consequences of copy number gain of the involved genes. The amplification of one gene, POLR1D, impacted cell proliferation, resulting in upregulation of VEGFA, an important regulator of angiogenesis which has been implicated in the resistance to bevacizumab. In several patients, we observed the emergence of this 13q12.2 amplicon under bevacizumab treatment, which was invariably associated with evolution of therapy resistance. Hence, we describe a novel resistance mechanism against a widely applied treatment in mCRC patients which will impact clinical management","abstract":"Bevacizumab is an approved anti-angiogenic drug for patients with metastasized colorectal cancer (mCRC) targeting VEGF. The survival benefit of anti-VEGF therapy in mCRC patients is limited to a few months and acquired resistance mechanisms are greatly unknown. Using plasma DNA, we studied the evolution of tumor genomes in a cohort of patients with mCRC (n=150) and observed a recurrent focal amplification (8.7% of cases) on chromosome 13q12.2. Analysis of TCGA data (n=619) suggested an association with later stages, which we confirmed by longitudinal plasma analyses. We defined the minimally amplified region and studied the mechanistic consequences of copy number gain of the involved genes. The amplification of one gene, POLR1D, impacted cell proliferation, resulting in upregulation of VEGFA, an important regulator of angiogenesis which has been implicated in the resistance to bevacizumab. In several patients, we observed the emergence of this 13q12.2 amplicon under bevacizumab treatment, which was invariably associated with evolution of therapy resistance. Hence, we describe a novel resistance mechanism against a widely applied treatment in mCRC patients which will impact clinical management","study_type":"Other","pubmed_ids":[32087735],"external_links":null,"is_released":true,"released_date":"2019-08-02T12:38:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003792","title":"Distinct Phenotypes of Human Intrahepatic and Extrahepatic Bile duct Organoids and their Applications for Biliary Disease Modeling","description":null,"abstract":"Bile draining by the bile duct system is paramount for good liver function. Diseases which compromise the integrity of the biliary tree are common and often life-threatening. Both intrahepatic and extrahepatic bile ducts contain distinct (stem) cell niches which are important for bile duct homeostasis and repair. A detailed characterization of the cell populations in the extrahepatic bile ducts has been lacking due to the inability of cell culture propagation. The aim of this study was to expand extrahepatic bile duct stem cells using the organoid culture system developed for intrahepatic bile duct cells. Extrahepatic bile duct (eBD)-organoids and intrahepatic (iBD) liver-derived organoids were initiated from paired biopsies of human common bile duct and liver tissue. Organoids of both origins were characterized on the basis of morphology and growth characteristics, gene and protein expression profiles, and their differentiation capacity towards mature cholangiocytes and hepatocytes. Although eBD organoids were very similar to iBD liver organoids, some differences in growth rate, organoid size and gene and protein expression were found. More strikingly, although both organoids could be differentiated towards a mature cholangiocyte phenotype, only iBD organoids can be directed to a mature hepatocyte phenotype. Of note, eBD organoids derived from a cystic fibrosis (CF) patient, harboring the same CFTR mutation (dF508-R1162X) as found in the patient, showed normal Ca2+-dependent Cl- channel and MDR-1 transporter activity but no CFTR channel activity. In conclusion, we here show feasibility of expanding eBD organoids with distinct properties when compared to iBD organoids. These eBD organoids may provide an excellent model for studying bile duct diseases and regenerative medicine.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-02T13:29:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003793","title":"Whole exome sequencing","description":null,"abstract":"Single crypts\nBulk crypt samples\nColitis-associated cancer","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003794","title":"Whole exome sequencing","description":null,"abstract":"Single crypts\nBulk crypt samples\nColitis-associated cancer","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003795","title":"Genome_wide_Interferon_Gamma_MHC_I_CRISPR_Cas9_screening_of_Human_Organoid_Lines","description":"The study will perform genome-wide loss-of-function CRISPR-Cas9 screens to identify tumour cell regulators of immune effector signaling.\n\n*Sequencing is performed on PCR products from the amplification of gRNA segments introduced into commercial cell lines. Cellular DNA or RNA are not sequenced. This data is defined as \"Other Biological/Biochemical Assay Data\" under the WTSI datasharing guidelines and consequently will be released at the time of publication and/or through faculty websites.","abstract":"The goal of this project is to perform genome-wide loss-of-function CRISPR-Cas9 screens to identify tumour cell regulators of immune effector signaling. These results will be used to identify new factors mediating tumour-immune response.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003796","title":"MutWP6__CRUK_Grand_Challenge_Mutographs_of_Cancer__Tobacco","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nWithin Mutographs, work lead by the Sanger Institute will investigate whether detection of somatic mutations and mutational signatures in circulating white blood cells can be developed into a practical, generic system for surveying and monitoring multiple different endogenous and exogenous exposures, providing an ‘observatory’ on somatic mutational processes in humans.\n\nWhole genome sequences are generated at the Wellcome Sanger Institute (Illumina HiSeqX). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nWithin Mutographs, work lead by the Sanger Institute will investigate whether detection of somatic mutations and mutational signatures in circulating white blood cells can be developed into a practical, generic system for surveying and monitoring multiple different endogenous and exogenous exposures, providing an ‘observatory’ on somatic mutational processes in humans.\n\nWhole genome sequences are generated at the Wellcome Sanger Institute (Illumina HiSeqX). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003797","title":"TRACERx: Exome sequencing data from a single patient with primary and metastatic samples","description":"TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC). This study looks explored primary and metastatic samples from a patient with paired CTC data.","abstract":"TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC). This study looks explored primary and metastatic samples from a patient with paired CTC data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003798","title":"Molecular profiling reclassifies adult astroblastoma into known and clinically distinct tumor entities with frequent MAPK pathway alterations","description":null,"abstract":"Aims and methods: astroblastoma is a rare glial brain tumor with singular morphology. Recurrent MN1-BEND2 fusions have been recently identified in most of pediatric cases. Adolescent and adult cases, however, remain molecularly poorly defined. Here, we performed clinical and molecular characterization of a retrospective cohort of 14 adult and one adolescent gliomas with astroblastic features. \nResults: strikingly, we found MN1 fusions a rare event in this age group (1/15). Using methylation profiling and targeted sequencing, most cases were reclassified as either pleomorphic xanthoastrocytomas (PXA) or high-grade glioma (HGG). PXA-like ABM show BRAF mutation (6/7 with V600E mutation and 1/7 with G466E mutation) and CD34 expression. Conversely, HGG-like ABM harbored specific mutations of diffuse midline glioma (2/5) or glioblastoma (3/5). These latter patients showed an unfavorable clinical course with significantly shorter overall survival (p = 0.027). MAPK pathway alterations (including FGFR fusion, BRAF and NF1 mutations) were present in 10 of 15 patients and overrepresented in the HGG group (3/5) compared to previously reported prevalence of these alterations in GBM and diffuse midline glioma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-08T16:56:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003799","title":"Characterization of a case of MPAL, T/myeloid with t(6;14)(q25;q32)","description":"The translocation between chr6q25 and chr14q32 has been rarely described in hematopoietic malignancies and BCL11B gene on chr14q32 is potentially involved in this translocation. The impact of this translocation on gene expression and the features of cases carrying this translocation are uncertain.  In this study, we characterized this translocation on a single case of T/myeloid MPAL carrying t(6;14)(q25;q32) using low-pass whole genome sequencing and RNA sequencing.","abstract":"The translocation between chr6q25 and chr14q32 has been rarely described in hematopoietic malignancies and BCL11B gene on chr14q32 is potentially involved in this translocation. The impact of this translocation on gene expression and the features of cases carrying this translocation are uncertain.  In this study, we characterized this translocation on a single case of T/myeloid MPAL carrying t(6;14)(q25;q32) using low-pass whole genome sequencing and RNA sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003800","title":"Methylation CYLD cutaneous syndrome","description":"Patients with CYLD cutaneous syndrome (CCS; syn. Brooke-Spiegler syndrome) carry germline mutations in the tumor suppressor CYLD and develop multiple skin tumors with diverse histophenotypes. We comprehensively profiled the genomic landscape of 42 benign and malignant tumors across 13 individuals from four multigenerational families. Novel recurrent mutations were found in epigenetic modifiers DNMT3A and BCOR in 29% of benign tumors. Multi-level and microdissected sampling strikingly reveal that many clones with different DNMT3A mutations exist in these benign tumors, suggesting that intra-tumor heterogeneity is common. Integrated genomic, methylation and transcriptomic profiling in selected tumours suggest that isoform specific DNMT3A2 mutations are associated with dysregulated Wnt/ß-catenin pathway signaling. Phylogenetic and mutational signature analyses confirm cylindroma pulmonary metastases from primary skin tumours. These findings add novel dimensions to existing paradigms of cutaneous tumorigenesis and metastasis.","abstract":"Patients with CYLD cutaneous syndrome (CCS; syn. Brooke-Spiegler syndrome) carry germline mutations in the tumor suppressor CYLD and develop multiple skin tumors with diverse histophenotypes. We comprehensively profiled the genomic landscape of 42 benign and malignant tumors across 13 individuals from four multigenerational families. Novel recurrent mutations were found in epigenetic modifiers DNMT3A and BCOR in 29% of benign tumors. Multi-level and microdissected sampling strikingly reveal that many clones with different DNMT3A mutations exist in these benign tumors, suggesting that intra-tumor heterogeneity is common. Integrated genomic, methylation and transcriptomic profiling in selected tumours suggest that isoform specific DNMT3A2 mutations are associated with dysregulated Wnt/ß-catenin pathway signaling. Phylogenetic and mutational signature analyses confirm cylindroma pulmonary metastases from primary skin tumours. These findings add novel dimensions to existing paradigms of cutaneous tumorigenesis and metastasis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-08T22:04:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003801","title":"Ulcerative colitis study - WES data","description":"Whole Exome Sequencing data of Single crypts, bulk crypt samples, and colitis-associated cancer.","abstract":"Whole Exome Sequencing data of Single crypts, bulk crypt samples, and colitis-associated cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-09T13:09:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003802","title":"Ulcerative colitis study - RNAseq data","description":"RNAseq data of rectal epithelial cells from Nfkbiz cKO and control mice after DSS administration.","abstract":"RNAseq data of rectal epithelial cells from Nfkbiz cKO and control mice after DSS administration.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-09T13:09:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003803","title":"Spatial Heterogeneity in CLL","description":"A whole-genome/exome sequencing (WGS/WES) characterization of the spatial heterogeneity found in chronic lymphocytic leukemia (CLL) at diagnosis. Fifteen synchronous peripheral blood and lymph node samples were analyzed by WGS (n=2) or WES (n=13). Subtle differences in the global architecture of the tumor at peripheral blood and lymph node were observed only in a fraction of patients. Spatial heterogeneity was not found among the well-established CLL driver alterations.","abstract":"A whole-genome/exome sequencing (WGS/WES) characterization of the spatial heterogeneity found in chronic lymphocytic leukemia (CLL) at diagnosis. Fifteen synchronous peripheral blood and lymph node samples were analyzed by WGS (n=2) or WES (n=13). Subtle differences in the global architecture of the tumor at peripheral blood and lymph node were observed only in a fraction of patients. Spatial heterogeneity was not found among the well-established CLL driver alterations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-09T17:12:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003804","title":"Comprehensive molecular profiling of high-grade serous ovarian cancer","description":"The diversity and heterogeneity within high-grade serous ovarian cancer (HGSC) is not well understood. Here, we performed comprehensive molecular analysis, including high-pass whole genome sequencing, targeted deep sequencing, RNA sequencing, reverse phase protein arrays and immune assessment, on primary and metastatic sites from highly clinically annotated HGSC samples. Samples were obtained pre-treatment based on a laparoscopic triage algorithm from patients who underwent R0 tumor debulking, or received neoadjuvant chemotherapy (NACT) with excellent or poor response.","abstract":"The diversity and heterogeneity within high-grade serous ovarian cancer (HGSC) is not well understood. Here, we performed comprehensive molecular analysis, including high-pass whole genome sequencing, targeted deep sequencing, RNA sequencing, reverse phase protein arrays and immune assessment, on primary and metastatic sites from highly clinically annotated HGSC samples. Samples were obtained pre-treatment based on a laparoscopic triage algorithm from patients who underwent R0 tumor debulking, or received neoadjuvant chemotherapy (NACT) with excellent or poor response.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-12T10:22:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003805","title":"Celiac disease meta-analysis","description":"Celiac disease (CeD) is a common immune-mediated disease of the small intestine that is triggered by exposure to dietary gluten. While the HLA locus plays a major role in disease susceptibility, 39 non-HLA loci were also identified in a study of 24,269 individuals. We now build on this earlier study by adding 4,125  additional Caucasian samples including an Argentinian cohort genotyped on the Immunochip. In doing so, we not only confirm the previous associations, we also identify two novel independent genome-wide significant associations.","abstract":"Celiac disease (CeD) is a common immune-mediated disease of the small intestine that is triggered by exposure to dietary gluten. While the HLA locus plays a major role in disease susceptibility, 39 non-HLA loci were also identified in a study of 24,269 individuals. We now build on this earlier study by adding 4,125  additional Caucasian samples including an Argentinian cohort genotyped on the Immunochip. In doing so, we not only confirm the previous associations, we also identify two novel independent genome-wide significant associations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-13T10:17:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003806","title":"Integration of intra-sample contextual error modeling for improved detection of somatic mutations","description":null,"abstract":"Sensitive mutation detection by next generation sequencing is of great importance for early cancer detection, monitoring minimal residual disease (MRD), and guiding precision oncology. Nevertheless, due to technical artefacts introduced during library preparation and sequencing steps as well as sub-optimal mutation calling analysis, the detection of variants with low allele frequency at high specificity is still problematic. Herein we validate a new practical error modeling technique for improved detection of single nucleotide variant (SNV) from hybrid-capture and targeted next generation sequencing.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-13T23:06:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003807","title":"Delineating intratumoral heterogeneity and immune escape in esophageal squamous cell by multi-omics seuqencing","description":"Delineating intratumoral heterogeneity and immune escape in esophageal squamous cell by multi-omics seuqencing","abstract":"Delineating intratumoral heterogeneity and immune escape in esophageal squamous cell by multi-omics seuqencing","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003808","title":"Congenital_melanocyte_disorders_in_children","description":"To allow phylogenetic mapping of embryonological lineages and determination of the timing of key somatic mutation, whole genome sequencing will be performed on single cell clones from different tissues form two human subjects with congenital melanocytic naevus syndrome.","abstract":"To allow phylogenetic mapping of embryonological lineages and determination of the timing of key somatic mutation, whole genome sequencing will be performed on single cell clones from different tissues form two human subjects with congenital melanocytic naevus syndrome.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003809","title":"Whole-exome sequencing of Fanconi anemia-like inherited bone marrow failure syndrome","description":"We identified three fibroblast cultures derived from aplastic anemia patients in the Japanese Cancer Research Resources Bank (JCRB) Cell Bank that showed high levels of sister chromatid exchanges (SCEs) in PHA-stimulated lymphoblasts. To elucidate the genetic basis of the high SCE, we carried out whole exome sequencing of these samples. Subsequently, germline variants were analysed for these patients.","abstract":"We identified three fibroblast cultures derived from aplastic anemia patients in the Japanese Cancer Research Resources Bank (JCRB) Cell Bank that showed high levels of sister chromatid exchanges (SCEs) in PHA-stimulated lymphoblasts. To elucidate the genetic basis of the high SCE, we carried out whole exome sequencing of these samples. Subsequently, germline variants were analysed for these patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-14T09:02:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003810","title":"Human_Brain_Single_Nuclei_Seqeuncing_From_Biopsy_Samples","description":"We obtained human brain biopsies from patients undergoing brain surgeries. The samples were snap frozen and nuclei extracted by Dounce homogenization, then filtered and FACS purified. Finally, the FACS sorted individual nuclei were used for either 10x and NEB/SMARTseq RNA sequncing library construction. \n\nThe main goal of study is the characterization of brain cell types (from brain biopsy samples) at different life stages.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We obtained human brain biopsies from patients undergoing brain surgeries. The samples were snap frozen and nuclei extracted by Dounce homogenization, then filtered and FACS purified. Finally, the FACS sorted individual nuclei were used for either 10x and NEB/SMARTseq RNA sequncing library construction. \n\nThe main goal of study is the characterization of brain cell types (from brain biopsy samples) at different life stages.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003811","title":"Molecular characterisation of platinum-resistant testicular germ cell tumours","description":"We undertook whole-exome sequencing and molecular inversion probe analyses in testicular germ cell tumours from patients with platinum-resistant disease.","abstract":"We undertook whole-exome sequencing and molecular inversion probe analyses in testicular germ cell tumours from patients with platinum-resistant disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003812","title":"Single cell sequencing: Capturing the origin and dynamics of chromosomal copy-number heterogeneity","description":null,"abstract":"Shallow whole-genome sequencing of single cells from individual clonal (patient-derived colorectal cancer) organoids was performed to investigate the degree of copy-number heterogeneity that emerges and propagates during clonal organoid outgrowth of a single cancerous cell. Selected single cells were sequenced with higher coverage. In addition, daughter cells were isolated to directly link mitotic chromatin errors to chromosomal copy number changes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-16T08:08:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003813","title":"The Precision Medicine in Liver Cancer across an Asia-pacific NETwork (PLANET)","description":"Hepatocellular carcinoma (HCC) is the 2nd most important cause of cancer deaths in the world. The outcomes of treatment in HCC are poor compared to other common cancers because there are no good systemic therapy drugs. We designed a prospective study that will involve 5 different sites within the established Asia-Pacific Hepatocellular Carcinoma Trials Group to study both the genetics as well as immune profiles of HCC in different ethnicities. In this study, patients will be followed-up and at recurrence the tissues to understand the evolution of disease progression. Here, we presented both the genomic (DNA) and phenotypic (RNA) evolution for the first batch of 56 patients. The detailed findings will be listed in the corresponding publication soon.","abstract":"Hepatocellular carcinoma (HCC) is the 2nd most important cause of cancer deaths in the world. The outcomes of treatment in HCC are poor compared to other common cancers because there are no good systemic therapy drugs. We designed a prospective study that will involve 5 different sites within the established Asia-Pacific Hepatocellular Carcinoma Trials Group to study both the genetics as well as immune profiles of HCC in different ethnicities. In this study, patients will be followed-up and at recurrence the tissues to understand the evolution of disease progression. Here, we presented both the genomic (DNA) and phenotypic (RNA) evolution for the first batch of 56 patients. The detailed findings will be listed in the corresponding publication soon.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-19T05:23:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003814","title":"The Precision Medicine in Liver Cancer across an Asia-pacific NETwork (PLANET) - Intratumoural immune heterogeneity","description":"The clinical relevance of immune landscape intratumoural heterogeneity (immune-ITH) and its role in tumour evolution remain largely unexplored. Here, we uncover significant spatial and phenotypic immune–ITH from multiple tumour sectors and decipher its relationship with tumour evolution and disease progression in hepatocellular carcinomas (HCC). Immune–ITH is associated with tumour transcriptomic-ITH, mutational burden, and distinct immune microenvironments. Tumours with low immune–ITH experience higher immunoselective pressure and escape via loss of heterozygosity in human leukocyte antigens and immunoediting. Instead, the tumours with high immune-ITH evolve to a more immunosuppressive/exhausted microenvironment. This gradient of immune pressure along with immune-ITH represents a hallmark of tumour evolution, which is closely linked to the transcriptome-immune networks that contributes to disease progression and immune inactivation. Remarkably, high immune-ITH and its transcriptomic signature are predictive for worse clinical outcome in HCC patients. This in-depth investigation of ITH provides evidence on tumour-immune co-evolution along HCC progression.","abstract":"The clinical relevance of immune landscape intratumoural heterogeneity (immune-ITH) and its role in tumour evolution remain largely unexplored. Here, we uncover significant spatial and phenotypic immune–ITH from multiple tumour sectors and decipher its relationship with tumour evolution and disease progression in hepatocellular carcinomas (HCC). Immune–ITH is associated with tumour transcriptomic-ITH, mutational burden, and distinct immune microenvironments. Tumours with low immune–ITH experience higher immunoselective pressure and escape via loss of heterozygosity in human leukocyte antigens and immunoediting. Instead, the tumours with high immune-ITH evolve to a more immunosuppressive/exhausted microenvironment. This gradient of immune pressure along with immune-ITH represents a hallmark of tumour evolution, which is closely linked to the transcriptome-immune networks that contributes to disease progression and immune inactivation. Remarkably, high immune-ITH and its transcriptomic signature are predictive for worse clinical outcome in HCC patients. This in-depth investigation of ITH provides evidence on tumour-immune co-evolution along HCC progression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-19T06:54:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003815","title":"Human_iPS_WT_KO_derived_macrophages_and_Klebsiella","description":"We want to analyse the effect of specific mutations in Inflammasome genes on macrophages derived from human iPS cells on infection with Klebsiella species\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We will analyse transcriptomics data from WT and gene KO Kolf2 human iPS derived macrophages after infection with various species of Klebsiella","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003816","title":"Epigenetic and metabolomic data from type 2 diabetes adolescents","description":"Objective: Rates of type 2 diabetes (T2D) among adolescents are on the rise. Epigenetic changes could be associated with the\nmetabolic alterations in adolescents with T2D.\nMethods: We performed a cross-sectional integrated analysis of DNA methylation data from peripheral blood mononuclear cells\nwith serum metabolomic data from First Nation adolescents with T2D and controls participating in the Improving Renal\nComplications in Adolescents with type 2 diabetes through REsearch (iCARE) cohort study, to explore the molecular changes in\nadolescents with T2D.\nResults: Our analysis showed that 43 serum metabolites and 36 differentially methylated regions (DMR) were associated with T2D. Several DMRs were located near the transcriptional start site of genes with established roles in metabolic disease and associated with altered serum metabolites (e.g. glucose, leucine, and gamma-glutamylisoleucine). These included the free fatty acid receptor-1 (FFAR1), upstream transcription factor-2 (USF2), and tumor necrosis factor-related protein-9 (C1QTNF9), among others.\nConclusions: We identified DMRs and metabolites that merit further investigation to determine their significance in controlling\ngene expression and metabolism which could define T2D risk in adolescents.","abstract":"Objective: Rates of type 2 diabetes (T2D) among adolescents are on the rise. Epigenetic changes could be associated with the\nmetabolic alterations in adolescents with T2D.\nMethods: We performed a cross-sectional integrated analysis of DNA methylation data from peripheral blood mononuclear cells\nwith serum metabolomic data from First Nation adolescents with T2D and controls participating in the Improving Renal\nComplications in Adolescents with type 2 diabetes through REsearch (iCARE) cohort study, to explore the molecular changes in\nadolescents with T2D.\nResults: Our analysis showed that 43 serum metabolites and 36 differentially methylated regions (DMR) were associated with T2D. Several DMRs were located near the transcriptional start site of genes with established roles in metabolic disease and associated with altered serum metabolites (e.g. glucose, leucine, and gamma-glutamylisoleucine). These included the free fatty acid receptor-1 (FFAR1), upstream transcription factor-2 (USF2), and tumor necrosis factor-related protein-9 (C1QTNF9), among others.\nConclusions: We identified DMRs and metabolites that merit further investigation to determine their significance in controlling\ngene expression and metabolism which could define T2D risk in adolescents.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-19T23:10:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003817","title":"Functional analysis of GATA2 synonymous mutations","description":"Germline mutations in SAMD9 and SAMD9L (SAMD9/9L) genes predispose to myelodysplastic syndromes (MDS) and show high prevalence in pediatric MDS with monosomy 7. Here, we studied an international cohort of children with primary MDS to assess the prevalence, hematological features, genetics, clonal evolution and clinical outcome in patients with germline SAMD9/9L mutations compared to pediatric MDS with either germline GATA2 mutations or pediatric MDS with wildtype status in SAMD9/9L and GATA2 genes","abstract":"Germline mutations in SAMD9 and SAMD9L (SAMD9/9L) genes predispose to myelodysplastic syndromes (MDS) and show high prevalence in pediatric MDS with monosomy 7. Here, we studied an international cohort of children with primary MDS to assess the prevalence, hematological features, genetics, clonal evolution and clinical outcome in patients with germline SAMD9/9L mutations compared to pediatric MDS with either germline GATA2 mutations or pediatric MDS with wildtype status in SAMD9/9L and GATA2 genes","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-20T15:45:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003818","title":"Lothian Birth Cohort 1921 whole genome sequencing study","description":"297 members of the Lothian Birth Cohort 1921 (LBC1921) were sequenced using the Illumina HiSeq X platform. The LBC1921 are a relatively healthy cohort of  550 individuals who underwent cognitive and medical testing at a mean age of 79.1 (SD=0.6) years. They have since undergone four further waves of testing, approximately three years apart.","abstract":"297 members of the Lothian Birth Cohort 1921 (LBC1921) were sequenced using the Illumina HiSeq X platform. The LBC1921 are a relatively healthy cohort of  550 individuals who underwent cognitive and medical testing at a mean age of 79.1 (SD=0.6) years. They have since undergone four further waves of testing, approximately three years apart.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-20T16:23:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003819","title":"Lothian Birth Cohort 1936 whole genome sequencing study","description":"1075 members of the Lothian Birth Cohort 1936 (LBC1936) were sequenced using the Illumina HiSeq X platform. The LBC1936 are a relatively healthy cohort of 1091 individuals who underwent cognitive and medical testing at a mean age of 69.5 (SD=0.8) years. They have since undergone four further waves of testing, approximately three years apart.","abstract":"1075 members of the Lothian Birth Cohort 1936 (LBC1936) were sequenced using the Illumina HiSeq X platform. The LBC1936 are a relatively healthy cohort of 1091 individuals who underwent cognitive and medical testing at a mean age of 69.5 (SD=0.8) years. They have since undergone four further waves of testing, approximately three years apart.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-20T16:23:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003820","title":"Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML","description":"This study assessed molecular determinants of response in a cohort of patients with AML that were treated with venetoclax in combination with either DNA methyltransferase inhibitors or low dose cytarabine. RNA sequencing was performed on 31 patients from three different response classes [10 Group A - Durable remission (n=10), Group B - Relapsed (n=10) and Group C - Refractory (n=11)]. Library preparation and sequencing was performed at the Australian Genome Research Facility, using the Truseq Stranded mRNA library kit. Technical and batch replicate samples are included, and these replicates are designated in the sample name. Gene count data are provided with the original publication. The use of the sequencing data is subject to a data transfer agreement and is restricted to ethically approved research into blood cell malignancies and cannot be used to assess germline variants.","abstract":"This study assessed molecular determinants of response in a cohort of patients with AML that were treated with venetoclax in combination with either DNA methyltransferase inhibitors or low dose cytarabine. RNA sequencing was performed on 31 patients from three different response classes [10 Group A - Durable remission (n=10), Group B - Relapsed (n=10) and Group C - Refractory (n=11)]. Library preparation and sequencing was performed at the Australian Genome Research Facility, using the Truseq Stranded mRNA library kit. Technical and batch replicate samples are included, and these replicates are designated in the sample name. Gene count data are provided with the original publication. The use of the sequencing data is subject to a data transfer agreement and is restricted to ethically approved research into blood cell malignancies and cannot be used to assess germline variants.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-21T01:18:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003821","title":"Preservation of stemness in high-grade serous ovarian cancer organoids requires low Wnt environment","description":"High-grade serous ovarian cancer (HGSOC) likely originates from the fallopian tube (FT) epithelium, but advanced stages are mostly found outside the FT. We used ex-vivo cultures of HGSOC  and knock-out of tumor suppressors in FT organoids to study changes in epithelial cells and niche requirements for normal and transformed FT cells. We found that transformed cells require BMP signaling and are growth arrested in Wnt rich  medium.","abstract":"High-grade serous ovarian cancer (HGSOC) likely originates from the fallopian tube (FT) epithelium, but advanced stages are mostly found outside the FT. We used ex-vivo cultures of HGSOC  and knock-out of tumor suppressors in FT organoids to study changes in epithelial cells and niche requirements for normal and transformed FT cells. We found that transformed cells require BMP signaling and are growth arrested in Wnt rich  medium.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-21T16:28:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003822","title":"Epigenomics and Single-cell Sequencing Define a Developmental Hierarchy in Langerhans Cell Histiocytosis","description":"Langerhans cell histiocytosis (LCH) is a rare neoplasm predominantly affecting children. It occupies a hybrid position between cancers and inflammatory diseases, and it provides an attractive model for studying cancer development. To explore the molecular mechanisms underlying the pathophysiology of LCH and its characteristic clinical heterogeneity, we investigated the transcriptomic and epigenomic diversity in primary LCH lesions. Using single-cell RNA sequencing, we identified multiple recurrent types of LCH cells within these biopsies, including putative LCH progenitor cells and several subsets of differentiated LCH cells. We confirmed the presence of proliferative LCH cells in all analysed biopsies using immunohistochemistry, and we defined   an epigenomic and gene-regulatory basis of the different LCH cell subsets by chromatin accessibility profiling. In summary, our single-cell analysis of LCH uncovered an unexpected degree of cellular, transcriptomic, and epigenomic heterogeneity among LCH cells, indicative of complex developmental hierarchies in LCH lesions.","abstract":"Langerhans cell histiocytosis (LCH) is a rare neoplasm predominantly affecting children. It occupies a hybrid position between cancers and inflammatory diseases, and it provides an attractive model for studying cancer development. To explore the molecular mechanisms underlying the pathophysiology of LCH and its characteristic clinical heterogeneity, we investigated the transcriptomic and epigenomic diversity in primary LCH lesions. Using single-cell RNA sequencing, we identified multiple recurrent types of LCH cells within these biopsies, including putative LCH progenitor cells and several subsets of differentiated LCH cells. We confirmed the presence of proliferative LCH cells in all analysed biopsies using immunohistochemistry, and we defined   an epigenomic and gene-regulatory basis of the different LCH cell subsets by chromatin accessibility profiling. In summary, our single-cell analysis of LCH uncovered an unexpected degree of cellular, transcriptomic, and epigenomic heterogeneity among LCH cells, indicative of complex developmental hierarchies in LCH lesions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-22T13:14:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003823","title":"Gene_epression_regulation_in_cytokine_induced_immune_cell_states","description":"We isolated T cells and monocotyes from healthy platelet donors and cultured them in resting and stimulated conditions with addition of a range of cytokines. We performed RNA sequencing to assess impact of different disease-relevant cytokines upon immune cell responses.","abstract":"Genome wide association studies of autoimmune disease have identified many risk loci implicated in T cell and macrophage activation, differentiation and function. However, most identified risk variants are outside protein coding genes and additionally their activity may only be expressed in specific cell subsets and under limited conditions. Given that the inflammation and autoimmune tissue distruction is driven by the local production of cytokines, we investigated cytokine induced changes to T cell and macrophage responses by using a combination of immunological and genomics approaches. We assessed the chromatin, transcriptional and proteomic signatures specific for each of the cytokine polarising conditions. These cellular profiles were used to map risk variants to the cytokine-induced cell states relevant for autoimmune diseases.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-23T10:17:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003824","title":"A mouse model xenograft was developed from a patient with Head and Neck Squamous Cell Cancer and then treated by drugs targeting the PIK3CA pathway.","description":"Mutations and amplifications in the PIK3CA gene are some of the most frequently seen alterations in head and neck squamous cell cancer (HNSCC). This project study the effect of a leading clinical drug that specifically targets the gene product of PIK3CA. Although this drug works well in HNSCC, it is anticipated that some patients will become resistant to it over time and will stop responding, as this has been observed when other 'targeted' drugs are used in other cancers. The goal here is to determine what molecular mechanisms are involved with mediating resistance over time to the PIK3CA drug. The drug is called \"BYL719\". A mouse xenograft model was created in this effect. Basically, a tumour from a patient with HNSCC was engrafted in multiple mice, and once it grew, the mice were treated with BYL719 or a vehicle (corn oil). Over time, the corn oil mice's tumours grow very quickly. The BYL719-treated mice's tumours are static for about the first 50 days of treatment (suggesting the drug is quite effective), but then begin to resume growth (suggesting they have become resistant to the drug). With the tumours collected from the mice at the end point of the study, we are using a multi-platform approach to figure out what the differences are in the BYL719-resistant tumours, compared to the corn oil tumours, primary tumour (never engrafted into mice) and the patient blood.","abstract":"Mutations and amplifications in the PIK3CA gene are some of the most frequently seen alterations in head and neck squamous cell cancer (HNSCC). This project study the effect of a leading clinical drug that specifically targets the gene product of PIK3CA. Although this drug works well in HNSCC, it is anticipated that some patients will become resistant to it over time and will stop responding, as this has been observed when other 'targeted' drugs are used in other cancers. The goal here is to determine what molecular mechanisms are involved with mediating resistance over time to the PIK3CA drug. The drug is called \"BYL719\". A mouse xenograft model was created in this effect. Basically, a tumour from a patient with HNSCC was engrafted in multiple mice, and once it grew, the mice were treated with BYL719 or a vehicle (corn oil). Over time, the corn oil mice's tumours grow very quickly. The BYL719-treated mice's tumours are static for about the first 50 days of treatment (suggesting the drug is quite effective), but then begin to resume growth (suggesting they have become resistant to the drug). With the tumours collected from the mice at the end point of the study, we are using a multi-platform approach to figure out what the differences are in the BYL719-resistant tumours, compared to the corn oil tumours, primary tumour (never engrafted into mice) and the patient blood.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003825","title":"Exome sequencing of Fibromyalgia patients","description":"Fibromyalgia is a complex disorder characterized by increased sensitivity to pain and extreme tiredness. It affects mostly women, and its causes are unknown. \nIn this study we have performed exome sequencing of 87 fibromyalgia cases, including some sibling pairs, to perform rare variant association analysis and identify fibromyalgia risk factors.\nA few of the included samples have been also included in a previous GWAS study.","abstract":"Fibromyalgia is a complex disorder characterized by increased sensitivity to pain and extreme tiredness. It affects mostly women, and its causes are unknown. \nIn this study we have performed exome sequencing of 87 fibromyalgia cases, including some sibling pairs, to perform rare variant association analysis and identify fibromyalgia risk factors.\nA few of the included samples have been also included in a previous GWAS study.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003826","title":"Exome sequencing of Fibromyalgia patients","description":"Fibromyalgia is a complex disorder characterized by increased sensitivity to pain and extreme tiredness. It affects mostly women, and its causes are unknown. \nIn this study we have performed exome sequencing of 87 fibromyalgia cases, including some sibling pairs, to perform rare variant association analysis and identify fibromyalgia risk factors.\nA few of the included samples have been also included in a previous GWAS study.","abstract":"Fibromyalgia is a complex disorder characterized by increased sensitivity to pain and extreme tiredness. It affects mostly women, and its causes are unknown. \nIn this study we have performed exome sequencing of 87 fibromyalgia cases, including some sibling pairs, to perform rare variant association analysis and identify fibromyalgia risk factors.\nA few of the included samples have been also included in a previous GWAS study.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-24T09:48:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003827","title":"eccDNA in maternal plasma","description":"We developed a new bioinformatics method for detecting the eccDNA in plasma. We revealed that the biological properties between eccDNA and linear DNA are different. eccDNA could be potentially provided as a new class of circulating biomarker.","abstract":"We developed a new bioinformatics method for detecting the eccDNA in plasma. We revealed that the biological properties between eccDNA and linear DNA are different. eccDNA could be potentially provided as a new class of circulating biomarker.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-26T04:18:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003828","title":"Genomic landscape and PD-1 blockade in Natural-killer/T cell lymphoma","description":"Natural killer/T-cell lymphoma (NKTL) is an aggressive malignancy with a predilection for Asian, Mexican and South American populations. With the exception of Japan, it is the most common mature T-cell lymphoma in Asia. NKTL presents as extranodal disease and mostly affects the upper aerodigestive tract. Neoplastic cells are invariably infected by the Epstein-Barr virus (EBV) and characterized by a cytotoxic phenotype. The genetic landscape of NKTL has been recently unraveled by discoveries describing recurring mutations altering the JAK-STAT pathway, epigenetic modifiers, the DDX3X gene and genetic predisposition in the HLA-DPB1 gene.The genomic landscape of NKTL has been interrogated by whole-exome sequencing, targeted sequencing and single nucleotide polymorphism arrays, but has yet been studied with whole-genome sequencing (WGS). In this study, we will use a combination of WGS, targeted-capture sequencing (TCS) and RNA sequencing data to explore the genetic landscape and its relevance to immunotherapy in NKTL","abstract":"Natural killer/T-cell lymphoma (NKTL) is an aggressive malignancy with a predilection for Asian, Mexican and South American populations. With the exception of Japan, it is the most common mature T-cell lymphoma in Asia. NKTL presents as extranodal disease and mostly affects the upper aerodigestive tract. Neoplastic cells are invariably infected by the Epstein-Barr virus (EBV) and characterized by a cytotoxic phenotype. The genetic landscape of NKTL has been recently unraveled by discoveries describing recurring mutations altering the JAK-STAT pathway, epigenetic modifiers, the DDX3X gene and genetic predisposition in the HLA-DPB1 gene.The genomic landscape of NKTL has been interrogated by whole-exome sequencing, targeted sequencing and single nucleotide polymorphism arrays, but has yet been studied with whole-genome sequencing (WGS). In this study, we will use a combination of WGS, targeted-capture sequencing (TCS) and RNA sequencing data to explore the genetic landscape and its relevance to immunotherapy in NKTL","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-26T07:27:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003829","title":"Clonal evolution in myelofibrosis during ruxolitinib therapy","description":null,"abstract":"Sequential samples from 15 MF patients (PMF n=8; post-ET/PV-MF n=7) before and after JAK inhibitor, ruxolitinib, treatment were analysed by whole-exome sequencing (WES). WES revealed acquisition of somatic mutations and copy number aberrations over time. Disease progression was associated with increased genetic heterogeneity and gain of RAS/RTK pathway mutations.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-26T13:15:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003830","title":"Deep multi-region whole-genome sequencing reveals heterogeneity and gene-by-environment interactions in treatment-naive, metastatic lung cancer","description":"Our understanding of genomic heterogeneity in lung cancer is largely based on the analysis of early-stage surgical specimens. Here we used endoscopic sampling of paired primary and intrathoracic metastatic tumors from 11 lung cancer patients to map genomic heterogeneity inoperable lung cancer with deep whole-genome sequencing. Intra-patient heterogeneity in driver or targetable mutations was predominantly in the form of copy number gain. Private mutation signatures, including patterns consistent with defects in homologous recombination, were highly variable both within and between patients. Irrespective of histotype, we observed a smaller than expected number of private mutations, suggesting that ancestral clones accumulated large mutation burdens immediately prior to metastasis. Single-region whole-genome sequencing of from 20 patients showed that tumors in ever-smokers with the strongest tobacco signatures were associated with germline variants in genes implicated in the repair of cigarette-induced DNA damage. Our results suggest that lung cancer precursors in ever-smokers accumulate large numbers of mutations prior to the formation of frank malignancy followed by rapid metastatic spread. In advanced lung cancer, germline variants in DNA repair genes may interact with the airway environment to influence the pattern of founder mutations, whereas similar interactions with the tumor microenvironment may play a role in the acquisition of mutations following metastasis.","abstract":"Our understanding of genomic heterogeneity in lung cancer is largely based on the analysis of early-stage surgical specimens. Here we used endoscopic sampling of paired primary and intrathoracic metastatic tumors from 11 lung cancer patients to map genomic heterogeneity inoperable lung cancer with deep whole-genome sequencing. Intra-patient heterogeneity in driver or targetable mutations was predominantly in the form of copy number gain. Private mutation signatures, including patterns consistent with defects in homologous recombination, were highly variable both within and between patients. Irrespective of histotype, we observed a smaller than expected number of private mutations, suggesting that ancestral clones accumulated large mutation burdens immediately prior to metastasis. Single-region whole-genome sequencing of from 20 patients showed that tumors in ever-smokers with the strongest tobacco signatures were associated with germline variants in genes implicated in the repair of cigarette-induced DNA damage. Our results suggest that lung cancer precursors in ever-smokers accumulate large numbers of mutations prior to the formation of frank malignancy followed by rapid metastatic spread. In advanced lung cancer, germline variants in DNA repair genes may interact with the airway environment to influence the pattern of founder mutations, whereas similar interactions with the tumor microenvironment may play a role in the acquisition of mutations following metastasis.","study_type":"Other","pubmed_ids":[30348992],"external_links":null,"is_released":true,"released_date":"2019-08-27T06:03:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003831","title":"Exome sequencing data for 40 cases of alopecia areata and vitiligo","description":"Sequencing of independent unrelated cases of alopecia areata (total/ universal) and vitiligo (&gt;10%, affected family member). DNA obtained from blood","abstract":"Sequencing of independent unrelated cases of alopecia areata (total/ universal) and vitiligo (&gt;10%, affected family member). DNA obtained from blood","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-27T09:41:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003832","title":"Delineating intratumoural heterogeneity and neoantigen-directed immune escape in Esophageal Squamous Cell Carcinoma","description":"Delineating intratumoural heterogeneity and neoantigen-directed immune escape in Esophageal Squamous Cell Carcinoma","abstract":"Delineating intratumoural heterogeneity and neoantigen-directed immune escape in Esophageal Squamous Cell Carcinoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-27T14:13:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003833","title":"Genetic heterogeneity highlighted by differential FDG-PET response in diffuse large B cell lymphoma","description":"The impact of spatial or intra-tumor heterogeneity (ITH) on treatment failure in DLBCL has been overlooked, reflecting a reliance on the diagnostic biopsy.  This study examined ITH in diffuse large B cell lymphoma (DLBCL) by profiling four different sites of disease from a single patient that demonstrated a spatially discordant response to immuno-chemotherapy. The cell of origin differed across the sites of disease, with the chemosensitive inguinal tumor classified as germinal center type (GCB) and the chemorefractory disease above the diaphragm as either activated B cell type (ABC) or unclassified DLBCL. All biopsies shared mutations in CREBBP, KMT2D and CARD11 supporting their role as early driver events with the inguinal (EZH2, STAT6, GNA13, IRF8, PIK3CD) and mediastinal (TP53) sites evolving separately. The study case sheds light on the underlying genetic ITH in patients with a discordant response to treatment and suggests that a single biopsy may not capture the full genomic complexity present and spatial variations need to be considered in biomarker-led clinical studies.","abstract":"The impact of spatial or intra-tumor heterogeneity (ITH) on treatment failure in DLBCL has been overlooked, reflecting a reliance on the diagnostic biopsy.  This study examined ITH in diffuse large B cell lymphoma (DLBCL) by profiling four different sites of disease from a single patient that demonstrated a spatially discordant response to immuno-chemotherapy. The cell of origin differed across the sites of disease, with the chemosensitive inguinal tumor classified as germinal center type (GCB) and the chemorefractory disease above the diaphragm as either activated B cell type (ABC) or unclassified DLBCL. All biopsies shared mutations in CREBBP, KMT2D and CARD11 supporting their role as early driver events with the inguinal (EZH2, STAT6, GNA13, IRF8, PIK3CD) and mediastinal (TP53) sites evolving separately. The study case sheds light on the underlying genetic ITH in patients with a discordant response to treatment and suggests that a single biopsy may not capture the full genomic complexity present and spatial variations need to be considered in biomarker-led clinical studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003834","title":"Genomic Analysis of Primary Plasma Cell Leukemia reveals Complex Structural Alterations and High Risk Mutational Patterns","description":"Primary plasma cell leukemia (pPCL) is a rare and aggressive form of multiple myeloma (MM) that is characterized by circulating plasma cells. Overall survival remains poor despite advances of anti-MM therapy. In an attempt to identify key biological mechanisms that result in the aggressive pPCL phenotype we performed whole exome sequencing of 23 patients with pPCL. For matched non-tumor control for each patient to exclude germline variants we used CD34+ cells from stem cell harvest (n=20) or cells obtained from buccal swabs (n=3). Tumor samples were from bone marrow derived CD138+ cells. Tumor samples were compared to the germline control to identify somatic abnormalities.","abstract":"Primary plasma cell leukemia (pPCL) is a rare and aggressive form of multiple myeloma (MM) that is characterized by circulating plasma cells. Overall survival remains poor despite advances of anti-MM therapy. In an attempt to identify key biological mechanisms that result in the aggressive pPCL phenotype we performed whole exome sequencing of 23 patients with pPCL. For matched non-tumor control for each patient to exclude germline variants we used CD34+ cells from stem cell harvest (n=20) or cells obtained from buccal swabs (n=3). Tumor samples were from bone marrow derived CD138+ cells. Tumor samples were compared to the germline control to identify somatic abnormalities.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-27T17:13:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003835","title":"Genome in a Bottle","description":null,"abstract":"In May, the National Institute of Standards and Technology (NIST) released its first 'genome in a bottle', a reference sample of DNA for validating human genome sequences. This so-called truth sequence comes from a decades-old sample donated by a Utah woman for (other) research purposes (NA12878 cell line), which, over the years, has been one of the most studied, and hence best-characterized, human samples. Seeing genomic medicine moving toward mainstream healthcare, researchers at NIST recognized the need for a reference human genome and assembled a private-public consortium in 2012 to create one. As detailed in a 2014 Nature Biotechnology paper (Nat. Biotechnol.32, 246–251, 2014), the group integrated and arbitrated among sequences from 14 data sets, five sequencing technologies, seven read mappers and three variant callers.","study_type":"Whole Genome Sequencing","pubmed_ids":[24531798,27271295,30858580,30936564],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003836","title":"Single_cell_genomics_and_transcriptomics_studies_on_human_oocytes","description":"Single cell genomics and transcriptomics studies will be undertaken on oocytes from healthy donors (different ages and different stages of differentiation) in order to study the extend of cellular heterogeneity and the contribution of acquired somatic genetic mutations to due to aging and its effect on genes transcription.","abstract":"Single cell genomics and transcriptomics studies will be undertaken on oocytes from healthy donors (different ages and different stages of differentiation) in order to study the extend of cellular heterogeneity and the contribution of acquired somatic genetic mutations to due to aging and its effect on genes transcription.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003837","title":"RNA-seq, WGS and WES of Hepatocellular carcinomas, enriched in fibrolamellar carcinomas","description":"DNAJB1-PRKACA fusion is a specific driver event in fibrolamellar carcinoma (FLC), a rare subtype of hepatocellular carcinoma (HCC) occurring in adolescents and young adults. In older patients, molecular determinants of HCC with mixed histological features of HCC and FLC (mixed-FLC/HCC) remain to be discovered.This study aims to molecularly caracterize mixed fibrolamellar hepatocellular carcinoma (mixed FLC/HCC) within the molecular liver tumors diversity, in respect of pure FLC and different HCC subtypes. This study reunites WGS data (n=3, Tumoral/Non-Tumoral pairs), WES data (n=43, Tumoral/Non-Tumoral pairs) and RNAseq data (n=66, Tumoral only). On a trascriptomic level, most of the mixed-FLC/HCC RNAseq clustered in a robust subgroup of tumors all showing mutation or translocation inactivating BAP1 that codes for the BRCA1 associated protein-1.","abstract":"DNAJB1-PRKACA fusion is a specific driver event in fibrolamellar carcinoma (FLC), a rare subtype of hepatocellular carcinoma (HCC) occurring in adolescents and young adults. In older patients, molecular determinants of HCC with mixed histological features of HCC and FLC (mixed-FLC/HCC) remain to be discovered.This study aims to molecularly caracterize mixed fibrolamellar hepatocellular carcinoma (mixed FLC/HCC) within the molecular liver tumors diversity, in respect of pure FLC and different HCC subtypes. This study reunites WGS data (n=3, Tumoral/Non-Tumoral pairs), WES data (n=43, Tumoral/Non-Tumoral pairs) and RNAseq data (n=66, Tumoral only). On a trascriptomic level, most of the mixed-FLC/HCC RNAseq clustered in a robust subgroup of tumors all showing mutation or translocation inactivating BAP1 that codes for the BRCA1 associated protein-1.","study_type":"Other","pubmed_ids":[31862487,32360197],"external_links":null,"is_released":true,"released_date":"2019-08-28T14:17:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003838","title":"UK Biobank whole genome sequencing study","description":"TODO: STUDY ABSTRACT AS IT COULD APPEAR IN A PUBLICATION","abstract":"TODO: STUDY ABSTRACT AS IT COULD APPEAR IN A PUBLICATION","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001003839","title":"Whole exome sequencing CYLD cutaneous syndrome","description":"Patients with CYLD cutaneous syndrome (CCS; syn. Brooke-Spiegler syndrome) carry germline mutations in the tumor suppressor CYLD and develop multiple skin tumors with diverse histophenotypes. We comprehensively profiled the genomic landscape of 42 benign and malignant tumors across 13 individuals from four multigenerational families. Novel recurrent mutations were found in epigenetic modifiers DNMT3A and BCOR in 29% of benign tumors. Multi-level and microdissected sampling strikingly reveal that many clones with different DNMT3A mutations exist in these benign tumors, suggesting that intra-tumor heterogeneity is common. Integrated genomic, methylation and transcriptomic profiling in selected tumours suggest that isoform specific DNMT3A2 mutations are associated with dysregulated Wnt/ß-catenin pathway signaling. Phylogenetic and mutational signature analyses confirm cylindroma pulmonary metastases from primary skin tumours. These findings add novel dimensions to existing paradigms of cutaneous tumorigenesis and metastasis.","abstract":"Patients with CYLD cutaneous syndrome (CCS; syn. Brooke-Spiegler syndrome) carry germline mutations in the tumor suppressor CYLD and develop multiple skin tumors with diverse histophenotypes. We comprehensively profiled the genomic landscape of 42 benign and malignant tumors across 13 individuals from four multigenerational families. Novel recurrent mutations were found in epigenetic modifiers DNMT3A and BCOR in 29% of benign tumors. Multi-level and microdissected sampling strikingly reveal that many clones with different DNMT3A mutations exist in these benign tumors, suggesting that intra-tumor heterogeneity is common. Integrated genomic, methylation and transcriptomic profiling in selected tumours suggest that isoform specific DNMT3A2 mutations are associated with dysregulated Wnt/ß-catenin pathway signaling. Phylogenetic and mutational signature analyses confirm cylindroma pulmonary metastases from primary skin tumours. These findings add novel dimensions to existing paradigms of cutaneous tumorigenesis and metastasis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-30T12:05:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003840","title":"Targeted sequencing CYLD cutaneous syndrome","description":"Patients with CYLD cutaneous syndrome (CCS; syn. Brooke-Spiegler syndrome) carry germline mutations in the tumor suppressor CYLD and develop multiple skin tumors with diverse histophenotypes. We comprehensively profiled the genomic landscape of 42 benign and malignant tumors across 13 individuals from four multigenerational families. Novel recurrent mutations were found in epigenetic modifiers DNMT3A and BCOR in 29% of benign tumors. Multi-level and microdissected sampling strikingly reveal that many clones with different DNMT3A mutations exist in these benign tumors, suggesting that intra-tumor heterogeneity is common. Integrated genomic, methylation and transcriptomic profiling in selected tumours suggest that isoform specific DNMT3A2 mutations are associated with dysregulated Wnt/ß-catenin pathway signaling. Phylogenetic and mutational signature analyses confirm cylindroma pulmonary metastases from primary skin tumours. These findings add novel dimensions to existing paradigms of cutaneous tumorigenesis and metastasis.","abstract":"Patients with CYLD cutaneous syndrome (CCS; syn. Brooke-Spiegler syndrome) carry germline mutations in the tumor suppressor CYLD and develop multiple skin tumors with diverse histophenotypes. We comprehensively profiled the genomic landscape of 42 benign and malignant tumors across 13 individuals from four multigenerational families. Novel recurrent mutations were found in epigenetic modifiers DNMT3A and BCOR in 29% of benign tumors. Multi-level and microdissected sampling strikingly reveal that many clones with different DNMT3A mutations exist in these benign tumors, suggesting that intra-tumor heterogeneity is common. Integrated genomic, methylation and transcriptomic profiling in selected tumours suggest that isoform specific DNMT3A2 mutations are associated with dysregulated Wnt/ß-catenin pathway signaling. Phylogenetic and mutational signature analyses confirm cylindroma pulmonary metastases from primary skin tumours. These findings add novel dimensions to existing paradigms of cutaneous tumorigenesis and metastasis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-30T12:05:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003841","title":"RNA sequencing CYLD cutaneous syndrome","description":"Patients with CYLD cutaneous syndrome (CCS; syn. Brooke-Spiegler syndrome) carry germline mutations in the tumor suppressor CYLD and develop multiple skin tumors with diverse histophenotypes. We comprehensively profiled the genomic landscape of 42 benign and malignant tumors across 13 individuals from four multigenerational families. Novel recurrent mutations were found in epigenetic modifiers DNMT3A and BCOR in 29% of benign tumors. Multi-level and microdissected sampling strikingly reveal that many clones with different DNMT3A mutations exist in these benign tumors, suggesting that intra-tumor heterogeneity is common. Integrated genomic, methylation and transcriptomic profiling in selected tumours suggest that isoform specific DNMT3A2 mutations are associated with dysregulated Wnt/ß-catenin pathway signaling. Phylogenetic and mutational signature analyses confirm cylindroma pulmonary metastases from primary skin tumours. These findings add novel dimensions to existing paradigms of cutaneous tumorigenesis and metastasis.","abstract":"Patients with CYLD cutaneous syndrome (CCS; syn. Brooke-Spiegler syndrome) carry germline mutations in the tumor suppressor CYLD and develop multiple skin tumors with diverse histophenotypes. We comprehensively profiled the genomic landscape of 42 benign and malignant tumors across 13 individuals from four multigenerational families. Novel recurrent mutations were found in epigenetic modifiers DNMT3A and BCOR in 29% of benign tumors. Multi-level and microdissected sampling strikingly reveal that many clones with different DNMT3A mutations exist in these benign tumors, suggesting that intra-tumor heterogeneity is common. Integrated genomic, methylation and transcriptomic profiling in selected tumours suggest that isoform specific DNMT3A2 mutations are associated with dysregulated Wnt/ß-catenin pathway signaling. Phylogenetic and mutational signature analyses confirm cylindroma pulmonary metastases from primary skin tumours. These findings add novel dimensions to existing paradigms of cutaneous tumorigenesis and metastasis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-08-30T12:05:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003842","title":"Osteosarcoma mate-pair and RNA-sequencing","description":"DNA mate pair and RNA sequencing data of conventional osteosarcomas. Mate pair libraries, with average insert sizes of 2-4 kb, were prepared for sequencing using the Nextera Mate Pair Library Preparation Kit. Paired-end 76 base pair reads were generated using an Illumina NextSeq 500 sequencing instrument. Total RNA was enriched for polyadenylated RNA using magnetic oligo(dT) beads. Enriched RNA was prepared for sequencing using the TruSeq RNA Sample Preparation Kit v2 and paired-end 151 base pair reads were generated from the cDNA libraries using an Illumina NextSeq 500 instrument.","abstract":"DNA mate pair and RNA sequencing data of conventional osteosarcomas. Mate pair libraries, with average insert sizes of 2-4 kb, were prepared for sequencing using the Nextera Mate Pair Library Preparation Kit. Paired-end 76 base pair reads were generated using an Illumina NextSeq 500 sequencing instrument. Total RNA was enriched for polyadenylated RNA using magnetic oligo(dT) beads. Enriched RNA was prepared for sequencing using the TruSeq RNA Sample Preparation Kit v2 and paired-end 151 base pair reads were generated from the cDNA libraries using an Illumina NextSeq 500 instrument.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-02T14:44:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003843","title":"C3 SNPs and outcome after lung transplantation","description":"Background: Development of chronic rejection is still a severe problem and causes high mortality rates after lung transplantation (LTx). Complement activation is important in the development of acute rejection (AR) and bronchiolitis obliterans syndrome, with C3 as a key complement factor. \nMethods: Since a single nucleotide polymorphism (SNP) in the C3 gene (rs2230199) is associated with long-term outcome after solid organ transplantation, we investigated this SNP in relation to LTx. In addition, we looked at local production of C3 by analyzing bronchoalveolar lavage fluid (BALF) of LTx patients using isoelectric focusing (IEF).   \nResults: We demonstrated the presence of C3 in BALF and showed that this is produced by the donor lung based on the genotype of SNP rs2230199. We also analyzed donor and patient SNP configurations and observed a significant association between the SNP configuration in patients and episodes of AR during 4-years follow-up. Survival analysis showed a lower AR-free survival in homozygous C3 slow patients (p=0.005). Furthermore, we found a significant association between the SNP configuration in donors and BOS development. Patients receiving a graft from a donor with at least one C3 fast variant for rs2230199 had an inferior BOS-free survival (p=0.044). \nConclusions: In conclusion, our data indicate local C3 production by donor lung cells. In addition, a single C3 SNP present in recipients affects short-term outcome after LTx, while this SNP in donors has an opposite effect on long-term outcome after LTx. These results could contribute to an improved risk stratification after transplantation.","abstract":"Background: Development of chronic rejection is still a severe problem and causes high mortality rates after lung transplantation (LTx). Complement activation is important in the development of acute rejection (AR) and bronchiolitis obliterans syndrome, with C3 as a key complement factor. \nMethods: Since a single nucleotide polymorphism (SNP) in the C3 gene (rs2230199) is associated with long-term outcome after solid organ transplantation, we investigated this SNP in relation to LTx. In addition, we looked at local production of C3 by analyzing bronchoalveolar lavage fluid (BALF) of LTx patients using isoelectric focusing (IEF).   \nResults: We demonstrated the presence of C3 in BALF and showed that this is produced by the donor lung based on the genotype of SNP rs2230199. We also analyzed donor and patient SNP configurations and observed a significant association between the SNP configuration in patients and episodes of AR during 4-years follow-up. Survival analysis showed a lower AR-free survival in homozygous C3 slow patients (p=0.005). Furthermore, we found a significant association between the SNP configuration in donors and BOS development. Patients receiving a graft from a donor with at least one C3 fast variant for rs2230199 had an inferior BOS-free survival (p=0.044). \nConclusions: In conclusion, our data indicate local C3 production by donor lung cells. In addition, a single C3 SNP present in recipients affects short-term outcome after LTx, while this SNP in donors has an opposite effect on long-term outcome after LTx. These results could contribute to an improved risk stratification after transplantation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-04T08:41:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003844","title":"Ultrasensitive amplicon barcoding for next-generation sequencing facilitating sequence error and amplification-bias correction","description":null,"abstract":"The ability to accurately characterize DNA variant proportions using PCR amplification is key to many genetic studies, including studying tumor heterogeneity, 16S microbiome, viral and immune receptor sequencing. We develop a novel generalizable ultrasensitive amplicon barcoding approach that significantly reduces the inflation/deflation of DNA variant proportions due to PCR amplification biases and sequencing errors. This method was applied to immune receptor sequencing, where it significantly improves the quality and estimation of diversity of the resulting library.","study_type":"Pooled Clone Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003845","title":"A single-cell atlas of human glioma","description":"Although tumor-propagating cells can be derived from glioblastomas (GBMs) of the proneural and mesenchymal subtypes, a glioma stem-like cell (GSC) of the classical subtype has not been identified. It is unclear if mesenchymal GSCs (mGSCs) and/or proneural GSCs (pGSCs) alone are sufficient to generate the spectrum of cellular heterogeneity observed in GBM. This study sheds light on a long-standing debate regarding lineage relationships among GSCs.","abstract":"Although tumor-propagating cells can be derived from glioblastomas (GBMs) of the proneural and mesenchymal subtypes, a glioma stem-like cell (GSC) of the classical subtype has not been identified. It is unclear if mesenchymal GSCs (mGSCs) and/or proneural GSCs (pGSCs) alone are sufficient to generate the spectrum of cellular heterogeneity observed in GBM. This study sheds light on a long-standing debate regarding lineage relationships among GSCs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-05T18:20:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003846","title":"Deciphering Intratumoral Molecular Heterogeneity in Clear Cell Renal Cell Carcinoma with a Radiogenomics Platform","description":"Intratumoral heterogeneity (ITH) challenges the molecular characterization of clear cell renal cell Carcinoma (ccRCC) with percutaneous biopsies and is a confounding factor in selection of molecular-targeted versus immune-based therapy. Magnetic Resonance (MR) Imaging can noninvasively assess the spatial landscape of the entire tumor. To validate MRI for ITH assessment, we implemented a radiogenomic platform through a systematic imaging based co-localization approach for multi region tissue acquisition from single tumors. We investigated if the spatial changes in imaging can predict the molecular changes using transcriptome and histopathological correlatives. Our study confirmed imaging heterogeneity as a predictor of molecular heterogeneity in ccRCC.","abstract":"Intratumoral heterogeneity (ITH) challenges the molecular characterization of clear cell renal cell Carcinoma (ccRCC) with percutaneous biopsies and is a confounding factor in selection of molecular-targeted versus immune-based therapy. Magnetic Resonance (MR) Imaging can noninvasively assess the spatial landscape of the entire tumor. To validate MRI for ITH assessment, we implemented a radiogenomic platform through a systematic imaging based co-localization approach for multi region tissue acquisition from single tumors. We investigated if the spatial changes in imaging can predict the molecular changes using transcriptome and histopathological correlatives. Our study confirmed imaging heterogeneity as a predictor of molecular heterogeneity in ccRCC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-05T20:38:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003847","title":"Longitudinal_profiling_of_the_immune_response_to_Plasmodium_vivax_in_naive_hosts_by_RNA_sequencing","description":"Plasmodium vivax offers unique challenges for control and elimination, and may prove a tougher hurdle to overcome than Plasmodium falciparum. And yet compared to P. falciparum we know very little about the innate and adaptive immune responses that need to be harnessed to reduce disease and transmission. We recently generated a blood bank of a new clonal field isolate of P. vivax (PvW1) for human challenge studies and used systems immunology tools to track the host response throughout infection and convalescence. As part of this study, RNA-sequencing was used to resolve changes in whole blood gene expression through time in 6 volunteers (7-9 time-points per volunteer). In summary, these data show that P. vivax induces two distinct transcriptional programmes in whole blood during and after infection. During infection, transcriptional profiling reveals the rapid mobilisation of an emergency myeloid response, which leads to systemic inflammation and the recruitment of all major T cell subsets into lymphoid tissues. Six days after infection, this innate response subsides and a transcriptional signature of proliferation is revealed. This most likely represents widespread activation of lymphocytes, which return to the circulation after parasite clearance - transcriptional profiling of T cells at this time-point could therefore reveal the outcomes of critical cell-cell interactions that take place within the spleen during infection. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Longitudinal profiling of the immune response to Plasmodium vivax in naive hosts by RNA-sequencing","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-06T12:12:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003848","title":"The evolutionary steps from primary to metastatic prostate cancer are largely uncharted, and the ability to use DNA present in body fluids as correlates of aggregate metastatic status is under-examined. We reconstructed phylogenies in ten prostate cancer patients with fatal disease using deep targeted sequencing of the prostate, adjacent and distant organs, as well as plasma, serum, and cerebrospinal fluid at various time points. A total of 163 samples are studied.","description":"The evolutionary steps from primary tumor to metastasis in prostate cancer are largely uncharted, and the ability to use serum, plasma, and cerebrospinal fluid as a correlate of aggregate metastatic tumor genomic status has not been tested. We used deep targeted sequencing to reconstruct tumor evolution in ten prostate cancer patients with fatal disease encompassing examination of the prostate and adjacent and distant organs, as well as plasma, serum, and cerebrospinal fluid at various time points. We show that there is substantial evolution from a common ancestor within the prostate that results in branching to multiple lineages which form an intermixed multi-clonal primary tumor mass. After the occurrence of key driver aberrations, one of these lineages will metastasize to multiple sites in a sequential fashion. These metastatic sites are then susceptible to being populated by cells from other intra-prostatic lineages or from other metastases. Genomic representation of metastases in body fluids is not uniform. Cerebrospinal fluid analysis can detect lineages not detected in circulating DNA, suggesting possible clinical utility.","abstract":"The evolutionary steps from primary tumor to metastasis in prostate cancer are largely uncharted, and the ability to use serum, plasma, and cerebrospinal fluid as a correlate of aggregate metastatic tumor genomic status has not been tested. We used deep targeted sequencing to reconstruct tumor evolution in ten prostate cancer patients with fatal disease encompassing examination of the prostate and adjacent and distant organs, as well as plasma, serum, and cerebrospinal fluid at various time points. We show that there is substantial evolution from a common ancestor within the prostate that results in branching to multiple lineages which form an intermixed multi-clonal primary tumor mass. After the occurrence of key driver aberrations, one of these lineages will metastasize to multiple sites in a sequential fashion. These metastatic sites are then susceptible to being populated by cells from other intra-prostatic lineages or from other metastases. Genomic representation of metastases in body fluids is not uniform. Cerebrospinal fluid analysis can detect lineages not detected in circulating DNA, suggesting possible clinical utility.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-06T14:12:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003849","title":"Evaluation of protocols for rRNA depletion-based RNA sequencing of nanogram inputs of mammalian total RNA","description":null,"abstract":"Next generation RNA-Sequencing (RNA-seq) is a flexible approach that can be applied to e.g. global quantification of transcript expression, the characterization of RNA structure such as splicing patterns and profiling of expressed mutations. Many RNA-seq protocols require up to microgram levels of total RNA input amounts to generate high quality data, and thus remain impractical for the limited starting material amounts typically obtained from rare cell populations, such as those from early developmental stages or from laser micro-dissected clinical samples. Here, we present an assessment of the contemporary ribosomal RNA depletion-based protocols, and identify those that are suitable for inputs as low as 1-10 ng of intact total RNA and 100-500 ng of partially degraded RNA from formalin-fixed paraffin-embedded tissues.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-07T01:21:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003850","title":"Discovering genetic causes of optic atrophy syndromes through whole exome sequencing","description":"The genetic defects leading to optic atrophy range from mitochondrial DNA (mtDNA) point mutations in Leber’s hereditary optic neuropathy (LHON), to dominant and recessive mutations affecting a cluster of nuclear genes implicated in mitochondrial dynamics. We performed WES in patients with an optic atrophy spectrum disorder, including retinal macular dystrophy and kidney insufficiency leading to transplantation, associated with mitochondrial DNA (mtDNA) depletion without accumulation of multiple deletions, to identify the genetic causes of this syndrome.","abstract":"The genetic defects leading to optic atrophy range from mitochondrial DNA (mtDNA) point mutations in Leber’s hereditary optic neuropathy (LHON), to dominant and recessive mutations affecting a cluster of nuclear genes implicated in mitochondrial dynamics. We performed WES in patients with an optic atrophy spectrum disorder, including retinal macular dystrophy and kidney insufficiency leading to transplantation, associated with mitochondrial DNA (mtDNA) depletion without accumulation of multiple deletions, to identify the genetic causes of this syndrome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-09T13:01:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003851","title":"Solve-RD Solving the Unsolved Rare Dieseases","description":"Solve-RD – solving the unsolved rare diseases is a research project funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No 779257 from 1 January 2018 to 31 March 2024. Six European Reference Networks (ERNs; ERN-RND, -ITHACA, -EuroNMD, -GENTURIS, -RITA and -EpiCare) contributed data and samples to one or more of the four cohorts for data re-analysis and novel omics. For more information see https://solve-rd.eu/results/solve-rd-data/.","abstract":"Solve-RD – solving the unsolved rare diseases is a research project funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No 779257 from 1 January 2018 to 31 March 2024. Six European Reference Networks (ERNs; ERN-RND, -ITHACA, -EuroNMD, -GENTURIS, -RITA and -EpiCare) contributed data and samples to one or more of the four cohorts for data re-analysis and novel omics. For more information see https://solve-rd.eu/results/solve-rd-data/.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-09T14:15:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003852","title":"Modeling glioblastoma invasion using human brain organoids and single-cell transcriptomics","description":"We performed scRNA-seq of patient-derived glioblastoma cells alone or after co-culture with human iPSC-derived cerebral organoid cells. Transcriptional changes implicated in the invasion process that are coherent across patient samples indicate that GBM cells reactively upregulate genes required for their dispersion. Potential interactions between GBM and organoid cells identified by an in silico receptor-ligand pairing screen suggest functional therapeutic targets.","abstract":"We performed scRNA-seq of patient-derived glioblastoma cells alone or after co-culture with human iPSC-derived cerebral organoid cells. Transcriptional changes implicated in the invasion process that are coherent across patient samples indicate that GBM cells reactively upregulate genes required for their dispersion. Potential interactions between GBM and organoid cells identified by an in silico receptor-ligand pairing screen suggest functional therapeutic targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-09T14:51:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003853","title":"Sequencing of an organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity.","description":"Kidney tumors are among the most common solid tumors in children, comprising several distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first pediatric cancer organoid biobank. It contains tumor and matching normal organoids from over 50 children with different subtypes of kidney cancer, including Wilms tumors, malignant rhabdoid tumors, renal cell carcinomas, and congenital mesoblastic nephromas. The malignant rhabdoid tumor organoids represent the first organoid model for tumors of non-epithelial origin. The tumor organoids retain key properties of native tumors, useful for revealing patient specific drug vulnerabilities. We further demonstrate that organoid cultures derived from Wilms tumors consist of multiple different cell types, including epithelial, stromal and blastemal-like. Our organoid biobank captures the cellular heterogeneity of pediatric kidney tumors, providing a representative collection of well-characterized models for basic cancer research, drug-screening, and personalized medicine.","abstract":"Kidney tumors are among the most common solid tumors in children, comprising several distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first pediatric cancer organoid biobank. It contains tumor and matching normal organoids from over 50 children with different subtypes of kidney cancer, including Wilms tumors, malignant rhabdoid tumors, renal cell carcinomas, and congenital mesoblastic nephromas. The malignant rhabdoid tumor organoids represent the first organoid model for tumors of non-epithelial origin. The tumor organoids retain key properties of native tumors, useful for revealing patient specific drug vulnerabilities. We further demonstrate that organoid cultures derived from Wilms tumors consist of multiple different cell types, including epithelial, stromal and blastemal-like. Our organoid biobank captures the cellular heterogeneity of pediatric kidney tumors, providing a representative collection of well-characterized models for basic cancer research, drug-screening, and personalized medicine.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-10T09:44:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003854","title":"Respiratory Microbiota of African Children","description":"Nasopharyngeal colonization dynamics with Streptococcus pneumoniae and associated antimicrobial-resistance in a South African birth cohort.","abstract":"Nasopharyngeal colonization dynamics with Streptococcus pneumoniae and associated antimicrobial-resistance in a South African birth cohort.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003855","title":"E-box distribution determines response of MYC-HDAC2 co-bound genes to class I HDAC inhibition in MYC-driven medulloblastoma","description":"The sensitivity of MYC amplified medulloblastoma to class I HDAC inhibition has been shown previously, however understanding the underlying molecular mechanism is crucial for selection of effective HDAC inhibitors for clinical use. Using co-immunoprecipitation, mass spectrometry and ChIP sequencing we show that HDAC2 is a cofactor of MYC in MYC amplified medulloblastoma. The MYC-HDAC2 complex is bound to genes defining the MYC-dependent transcriptional profile. Class I HDAC inhibition leads to stabilization and reduced DNA binding of MYC protein inducing a down-regulation of MYC activated genes (MAGs) and up-regulation of MYC repressed genes (MRGs). MAGs and MRGs are characterized by opposing biological functions and by distinct E-box distribution. We propose that inhibition of class I HDACs directly targets MYC´s transactivating and transrepressing function.","abstract":"The sensitivity of MYC amplified medulloblastoma to class I HDAC inhibition has been shown previously, however understanding the underlying molecular mechanism is crucial for selection of effective HDAC inhibitors for clinical use. Using co-immunoprecipitation, mass spectrometry and ChIP sequencing we show that HDAC2 is a cofactor of MYC in MYC amplified medulloblastoma. The MYC-HDAC2 complex is bound to genes defining the MYC-dependent transcriptional profile. Class I HDAC inhibition leads to stabilization and reduced DNA binding of MYC protein inducing a down-regulation of MYC activated genes (MAGs) and up-regulation of MYC repressed genes (MRGs). MAGs and MRGs are characterized by opposing biological functions and by distinct E-box distribution. We propose that inhibition of class I HDACs directly targets MYC´s transactivating and transrepressing function.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003856","title":"Targeted sequencing of patients affected by familial or sporadic Alzheimer's disease","description":"The  study aimed at identifying variants related to familial cases of Alzheimer's disease by comparing the mutational state of approximately 4000 genes associated to many known diseases (\"clinical exome\") in members of a family (n=7) of with members with dementia (n=2) and unaffected members (n=5)","abstract":"The  study aimed at identifying variants related to familial cases of Alzheimer's disease by comparing the mutational state of approximately 4000 genes associated to many known diseases (\"clinical exome\") in members of a family (n=7) of with members with dementia (n=2) and unaffected members (n=5)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-10T13:06:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003857","title":"WES of melanoma tumors treated with combined immune checkpoint blockade","description":"This study of pre-treatment melanoma tumor samples from patients subsequently treated with combined anti-CTLA-4 and anti-PD-1 checkpoint blockade sought to identify genomic biomarkers of response to therapy. A total of 26 tumor and matched normal samples underwent whole exome sequencing.","abstract":"This study of pre-treatment melanoma tumor samples from patients subsequently treated with combined anti-CTLA-4 and anti-PD-1 checkpoint blockade sought to identify genomic biomarkers of response to therapy. A total of 26 tumor and matched normal samples underwent whole exome sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-10T15:40:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003858","title":"Effect_of_genetic_variants_associated_with_risk_for_inflammatory_bowel_disease_on_cell_phenotype_and_function","description":"Over 240 single nucleotide polymorphisms (SNP) have been associated with inflammatory bowel disease (IBD), a family of diseases characterized by chronic inflammation of the gastro-intestinal track . The objective of this study is to investigate the effect of a selection of these IBD-associated variants on the phenotype and function of immune cells. Human primary cells will be isolated from blood, their genome will be manipulated by CRISPR/Cas9 editing and the resulting changes will be assessed by RNA-sequencing and functional work. Similarly, induced-pluripotent stem cells will be genetically edited to express the variants of interest and differentiated to relevant cell types before RNA-sequencing and functional work. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Inflammatory bowel disease (IBD) defines a family of diseases characterized by chronic inflammation of the gastro-intestinal track, namely Crohn's disease (CD) and ulcerative colitis (UC). Over 240 single nucleotide polymorphisms (SNP) have been associated with IBD by genome wide association studies (GWAS). Some of these GWAS hits are within genes well known to a have a role in the pathology of IBD, such as interleukin(IL)-23, SMAD3, JAK2 and IL-23 receptor. However, the majority of the hits are within genes whose role in IBD have not been investigated or more frequently in non-coding regions of the genome which are predicted, but not confirmed, to regulate gene expression. In order to address this issue, the genome of an induced pluripotent stem cell (iPSC) line will be edited with CRISPR/Cas9 to express either the reference or alternative alleles in a homologous or heterogenous manner, as well as knock-outs of the target regions. Single clones (approximately 300/variants for 6 variants) will be isolated from each CRISPR experiment and genotyped and validated by MiSeq. Additionaly, primary cells will be isolated from human blood and their genome manipulated through CRISPR/Cas9 editing. These genetically engineered primary or iPS cells will subsequently be differentiated or activated to relevant cell types, i.e macrophages, Tregs - and the changes in cellular phenotype or function will be observed by RNA-sequencing and functional work.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003859","title":"Exome and transcriptome sequencing of a B-cell progenitor acute lymphoblastic leukemia (ALL) patient relapsing 13 years later with refractory pro-B/mixed ALL.","description":null,"abstract":"Here, we report the case of a 6-yr-old patient, diagnosed with cytogenetically normal pre-B cell acute lymphoblastic leukemia (pre-B ALL) with 33% blasts in July 2003. He completed chemotherapy (CCG-1991) in 2006, achieving complete remission. In February of 2016, flow cytometry confirmed relapsing pre-B ALL with 86% blasts. Reinduction yielded the second remission in February 2018. In June 2018, exome and transcriptome sequencing of samples from 2003 (exome-only), 2016, and 2018 was performed. The 2003 sample revealed PAX5 and CDKN2A deletions and NRAS G12D. In contrast, his 2016 samples revealed compound heterozygous JAK2 mutations, IKZF1 deletion, CRLF2 overexpression, and IGH-CRLF2 fusion, all characteristic of poor prognosis, Philadelphia-chromosome-like (Ph-like) pre-B ALL. Prompted by these findings, surveillance flow cytometry in August 2018 confirmed 7% marrow blasts. Salvage chemotherapy yielded morphological remission at 2 wk, with persistent MRD over 2 mo. FISH and RNA sequencing confirmed the persistence of an IGH-CRLF2 fusion-positive clone surviving reinduction and salvage. An allogeneic stem cell transplant (allo-SCT) followed in October 2018. A posttransplant exome shows extensive chimerism, successful engraftment, and stable molecular remission. This case highlights the benefits of, and the need for, DNA and RNA sequence\nanalysis in late relapses, even for seemingly well-characterized cases. Ph-like ALL is a highrisk, chemorefractory disease; some cases respond to kinase inhibition, but high-throughput screening showed that our patient’s cells would likely not. Deep analysis of exome and transcriptome results at first relapse (2016) could have elided 2 yr of chemotherapy. As of August 2019, he remains in stable remission, with no evidence of leukemia or graftversus-host disease (GvHD).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003860","title":"Single cell phenotypic profiling of 27 DLBCL cases reveals marked inter- and intra-tumoral heterogeneity","description":"Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of non-Hodgkin lymphoma and is notorious for its clinical heterogeneity. Patient outcomes can be predicted by cell-of-origin (COO) classification, demonstrating that the underlying transcriptional signature of malignant B-cells informs biological behavior in the context of standard combination chemotherapy regimens. In the current study, we used mass cytometry (CyTOF) to examine tumor phenotypes at the protein level with single cell resolution in a collection of 27 diagnostic DLBCL biopsy specimens from treatment naïve patients. We found that malignant B-cells from each patient occupied unique regions in 37-dimensional phenotypic space with no apparent clustering of samples into discrete subtypes. Interestingly, variable MHC class II expression was found to be the greatest contributor to phenotypic diversity. Within individual tumors, a subset of cases showed multiple phenotypic subpopulations, and in one case we were able to demonstrate direct correspondence between protein-level phenotypic subsets and DNA mutation-defined subclones. In summary, CyTOF analysis can resolve both inter- and intra-tumoral heterogeneity among primary samples, and reveals that each case of DLBCL is unique and may be comprised of multiple, genetically distinct subclones.","abstract":"Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of non-Hodgkin lymphoma and is notorious for its clinical heterogeneity. Patient outcomes can be predicted by cell-of-origin (COO) classification, demonstrating that the underlying transcriptional signature of malignant B-cells informs biological behavior in the context of standard combination chemotherapy regimens. In the current study, we used mass cytometry (CyTOF) to examine tumor phenotypes at the protein level with single cell resolution in a collection of 27 diagnostic DLBCL biopsy specimens from treatment naïve patients. We found that malignant B-cells from each patient occupied unique regions in 37-dimensional phenotypic space with no apparent clustering of samples into discrete subtypes. Interestingly, variable MHC class II expression was found to be the greatest contributor to phenotypic diversity. Within individual tumors, a subset of cases showed multiple phenotypic subpopulations, and in one case we were able to demonstrate direct correspondence between protein-level phenotypic subsets and DNA mutation-defined subclones. In summary, CyTOF analysis can resolve both inter- and intra-tumoral heterogeneity among primary samples, and reveals that each case of DLBCL is unique and may be comprised of multiple, genetically distinct subclones.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-12T23:44:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003861","title":"IDENTIFICATION AND TARGETED MANAGEMENT OF A PATIENT WITH A NEURODEGENERATIVE DISORDER CAUSED BY BIALLELIC MUTATIONS IN SLC5A6","description":"We describe a sibling pair displaying an early infantile-onset, progressive neurodegenerative phenotype, with symptoms of developmental delay and epileptic encephalopathy developing from 12 to 14 months of age. Using whole exome sequencing, compound heterozygous variants were identified in SLC5A6, which encodes the sodium-dependent multivitamin transporter (SMVT) protein. SMVT is an important transporter of the B-group vitamins biotin, pantothenate and lipoate. The protein is ubiquitously expressed and has major roles in vitamin uptake in the digestive system, as well as transport of these vitamins across the blood-brain barrier. Pathogenicity of the identified variants was demonstrated by impaired biotin uptake of mutant SMVT. Identification of this vitamin transporter as the genetic basis of this disorder guided targeted therapeutic intervention, resulting clinically in improvement of the patient’s neurocognitive and neuromotor function. This is the second report of biallelic mutations in SLC5A6 leading to a neurodegenerative disorder due to impaired biotin, pantothenate and lipoate uptake. The genetic and phenotypic overlap of these cases confirms mutations in SLC5A6 as the genetic cause of this disease phenotype. Recognition of the genetic disorder caused by SLC5A6 mutations is essential for early diagnosis and to facilitate timely intervention by triple vitamin (biotin, pantothenate and lipoate) replacement therapy.","abstract":"We describe a sibling pair displaying an early infantile-onset, progressive neurodegenerative phenotype, with symptoms of developmental delay and epileptic encephalopathy developing from 12 to 14 months of age. Using whole exome sequencing, compound heterozygous variants were identified in SLC5A6, which encodes the sodium-dependent multivitamin transporter (SMVT) protein. SMVT is an important transporter of the B-group vitamins biotin, pantothenate and lipoate. The protein is ubiquitously expressed and has major roles in vitamin uptake in the digestive system, as well as transport of these vitamins across the blood-brain barrier. Pathogenicity of the identified variants was demonstrated by impaired biotin uptake of mutant SMVT. Identification of this vitamin transporter as the genetic basis of this disorder guided targeted therapeutic intervention, resulting clinically in improvement of the patient’s neurocognitive and neuromotor function. This is the second report of biallelic mutations in SLC5A6 leading to a neurodegenerative disorder due to impaired biotin, pantothenate and lipoate uptake. The genetic and phenotypic overlap of these cases confirms mutations in SLC5A6 as the genetic cause of this disease phenotype. Recognition of the genetic disorder caused by SLC5A6 mutations is essential for early diagnosis and to facilitate timely intervention by triple vitamin (biotin, pantothenate and lipoate) replacement therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-13T07:37:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003862","title":"Transcriptome_analysis_of_LCM_samples_","description":"We aim to set up a RNA pipeline for LCM samples to study transcriptome landscape of tumor and normal tissues. RNA was extracted from Lazer capture micro-dissection tissues and cDNA libraries were prepared with SMARTseq2 protocol. Libraries are pooled to be sequenced.","abstract":"In this study we aim to determine expression profile of tumor and normal tissues using LCM method.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-13T10:29:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003863","title":"Evolution_of_the_cancer_epigenome_in_myeloproliferative_neoplasms_TGS","description":"Targeted sequencing of haematopoietic colonies.","abstract":"Cancer clones emerge and evolve through somatic mutation acquisition and Darwinian selection, but the dynamics of clonal evolution remain poorly understood and predicting disease progression remains a real challenge. Genes that regulate the epigenome are clearly important targets of mutations in cancer, but the mechanisms by which they drive tumour evolution remain unknown.\nThe myeloproliferative neoplasms (MPN) are haematopoietic disorders that represent an excellent model to study genomic and epigenomic evolution in human cancers: (i) They are genetically well-defined with disease driving mutations in JAK2, CALR (which I described in 2013) or MPL, present alongside mutations in epigenetic regulators, such as, DNMT3A. (ii) Disease can be either stable, or progress to leukaemia or myelofibrosis, providing the opportunity to study the basis for these evolutionary differences, and (iii) Primary cells can be serially sampled at the clonal level enabling inter- and intra-clonal studies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-13T16:11:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003864","title":"Mutational profiling in MDS bulk mononuclear cells and hematopoietic stem cells","description":null,"abstract":"Whole-exome sequencing data of whole bone marrow mononuclear cells (MNCs), T-cells (non-tumoral controls) and hematopoietic stem cell (HSC) subpopulations was used to understand whether distinct MDS HSC and progenitor hierarchies are originated owing to the selective effects of mutations in specific genes on differentiation toward certain differentiation trajectories, and if HSC subpopulations other than LT-HSCs could be the stem-cell of origin of MDS. Briefly, MNC and T-cell exome sequencing data was used to identify somatic mutations in oncogenes/leukemia-relevant genes in each patient. In patients with HSC DNA available, identified mutations were back-tracked in specific HSC subpopulations.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003865","title":"Clonal burden in differentiated neutrophils in MDS patients treated with HMA","description":null,"abstract":"Whole bone marrow mononuclear cells (MNCs) and T-cells (non-tumoral controls) from MDS patients undergoing hematologic response to hypomethylating agents (HMAs) were exome-sequenced to identify somatic mutations in oncogenes/leukemia-relevant genes. FACS-purified terminally differentiated CD15+CD66b+ neutrophils from the same patients were exome-sequenced and variants identified in the MNCs were tracked in this cell population to determine clonal burden post-HMA induced differentiation.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003866","title":"Mutational profiling in MDS hematopoietic stem cells - targeted sequencing","description":null,"abstract":"DNA samples from sorted hematopoietic stem cells which had insufficient reads for a confident assessment of the presence/absence of a given variant in the corresponding cell subpopulation were re-sequenced with amplicon-based NGS using a panel of 295 leukemia-relevant genes (Takahashi K et al. 2017 Lancet Oncol).","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003867","title":"Mutational profiling in MDS bulk mononuclear cells and hematopoietic stem cells","description":null,"abstract":"Whole-exome sequencing data of whole bone marrow mononuclear cells (MNCs), T-cells (non-tumoral controls) and hematopoietic stem cell (HSC) subpopulations was used to understand whether distinct MDS HSC and progenitor hierarchies are originated owing to the selective effects of mutations in specific genes on differentiation toward certain differentiation trajectories, and if HSC subpopulations other than LT-HSCs could be the stem-cell of origin of MDS. Briefly, MNC and T-cell exome sequencing data was used to identify somatic mutations in oncogenes/leukemia-relevant genes in each patient. In patients with HSC DNA available, identified mutations were back-tracked in specific HSC subpopulations.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003868","title":"Clonal burden in differentiated neutrophils in MDS patients treated with HMA","description":null,"abstract":"Whole bone marrow mononuclear cells (MNCs) and T-cells (non-tumoral controls) from MDS patients undergoing hematologic response to hypomethylating agents (HMAs) were exome-sequenced to identify somatic mutations in oncogenes/leukemia-relevant genes. FACS-purified terminally differentiated CD15+CD66b+ neutrophils from the same patients were exome-sequenced and variants identified in the MNCs were tracked in this cell population to determine clonal burden post-HMA induced differentiation.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003869","title":"Mutational profiling in MDS hematopoietic stem cells - targeted sequencing","description":null,"abstract":"DNA samples from sorted hematopoietic stem cells which had insufficient reads for a confident assessment of the presence/absence of a given variant in the corresponding cell subpopulation were re-sequenced with amplicon-based NGS using a panel of 295 leukemia-relevant genes (Takahashi K et al. 2017 Lancet Oncol).","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003870","title":"Comprehensive Genomic Characterization of Gene Therapy-Induced T-cell Acute Lymphoblastic Leukemia (H007)","description":"Six out of ten patients in a hematopoietic stem cell gene therapy (GT) trial for Wiskott-Aldrich syndrome (WAS) developed T-cell acute lymphoblastic leukemia (T-ALL) associated with gamma-retroviral vector integration at the LMO2 locus. We hypothesized that detailed molecular analysis of T-ALL driven by temporally defined first deregulation of LMO2 might offer valuable insights into the pathogenesis of GT-associated and sporadic T-ALL (HIPO project 007). In all six patients whole-genome and transcriptome sequencing demonstrated that in addition to oncogenic chromosomal translocations involving the T-cell receptor loci, retrovirally induced leukemias faithfully recapitulated secondary genomic events observed in sporadic T-ALL. Multiple genetic events culminated in the development of a rapidly proliferating leukemic clone and onset of clinical manifestation at 1.3 to 5 years after infusion of the gene corrected transplant. These genetic alterations affected NOTCH1 and PI3K signaling, cell cycle regulation as wells as T-cell transcription factors LEF1 and TCF1. Two of the six cases displayed a phenotype reminiscent of early immature T-ALLs, and lacked additional T-ALL typical alterations. Our analysis shows that insertional mutagenesis involving the LMO2 locus triggers T-ALL development due to diverse genetic alterations in large parts, but not exclusively, in known T-ALL driver genes, demonstrating the molecular diversity of GT-associated T-ALL.","abstract":"Six out of ten patients in a hematopoietic stem cell gene therapy (GT) trial for Wiskott-Aldrich syndrome (WAS) developed T-cell acute lymphoblastic leukemia (T-ALL) associated with gamma-retroviral vector integration at the LMO2 locus. We hypothesized that detailed molecular analysis of T-ALL driven by temporally defined first deregulation of LMO2 might offer valuable insights into the pathogenesis of GT-associated and sporadic T-ALL (HIPO project 007). In all six patients whole-genome and transcriptome sequencing demonstrated that in addition to oncogenic chromosomal translocations involving the T-cell receptor loci, retrovirally induced leukemias faithfully recapitulated secondary genomic events observed in sporadic T-ALL. Multiple genetic events culminated in the development of a rapidly proliferating leukemic clone and onset of clinical manifestation at 1.3 to 5 years after infusion of the gene corrected transplant. These genetic alterations affected NOTCH1 and PI3K signaling, cell cycle regulation as wells as T-cell transcription factors LEF1 and TCF1. Two of the six cases displayed a phenotype reminiscent of early immature T-ALLs, and lacked additional T-ALL typical alterations. Our analysis shows that insertional mutagenesis involving the LMO2 locus triggers T-ALL development due to diverse genetic alterations in large parts, but not exclusively, in known T-ALL driver genes, demonstrating the molecular diversity of GT-associated T-ALL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-16T10:08:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003871","title":"Mel15 WES RNA sequencing data","description":"Our study presents a state of the art comprehensive genome- and proteome-based neoantigen discovery workflow and provides an in-depth analysis of neoantigens and autologous T-cell receptors with respective specificity demonstrating substantial information about quality of neoantigens and neoantigen-specific immune responses for the development of novel targeted immunotherapies.","abstract":"Our study presents a state of the art comprehensive genome- and proteome-based neoantigen discovery workflow and provides an in-depth analysis of neoantigens and autologous T-cell receptors with respective specificity demonstrating substantial information about quality of neoantigens and neoantigen-specific immune responses for the development of novel targeted immunotherapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003872","title":"VIKING Health Study - Shetland","description":"The Viking Health Study – Shetland, together with ORCADES collectively termed VIKING, aims to identify genes influencing risk factors for common diseases such as heart disease, diabetes, glaucoma and stroke. The genetic research cohort study in Shetland was established to identify genetic variants, both common and rare, increasing risk of disease. This isolated population has a number of characteristics, the most important being the very large number of distant relatives, which are favourable for the identification of rare variants influencing disease risk. This study describes PCR-free paired end whole genome sequencing (TruSeq DNA PCR-Free, Illumina) run on a HiSeqX platform at 30X coverage on 500 individuals from VIKING. Unrelated individuals from the largest families were selected first, followed by those from smaller families, until eventually related individuals were selected to best represent the variation in the full cohort.","abstract":"The Viking Health Study – Shetland, together with ORCADES collectively termed VIKING, aims to identify genes influencing risk factors for common diseases such as heart disease, diabetes, glaucoma and stroke. The genetic research cohort study in Shetland was established to identify genetic variants, both common and rare, increasing risk of disease. This isolated population has a number of characteristics, the most important being the very large number of distant relatives, which are favourable for the identification of rare variants influencing disease risk. This study describes PCR-free paired end whole genome sequencing (TruSeq DNA PCR-Free, Illumina) run on a HiSeqX platform at 30X coverage on 500 individuals from VIKING. Unrelated individuals from the largest families were selected first, followed by those from smaller families, until eventually related individuals were selected to best represent the variation in the full cohort.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-17T14:43:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003873","title":"Engineered nasal cartilage for the repair of osteoarthritic knee cartilage defects","description":null,"abstract":"Osteoarthritis (OA) is the most prevalent joint disorder causing pain and disability, predominantly in the ageing population but also in young individuals. Despite enormous efforts over the last decades, no single disease-modifying or regenerative approach is available for its management. Current treatments are limited to alleviate symptoms, e.g. with anti-inflammatory drugs, until at the end stage of the disease the degenerated joint is replaced by a prosthetic implant. In this study we evaluate the feasibility to treat degenerative cartilage defects using Nasal chondrocyte-based Tissue Engineered Cartilage (N-TEC). When exposed to inflammatory stimuli as those found in osteoarthritic joints, we demonstrate that N-TEC maintained the cartilaginous properties in vitro, and positively influenced the inflammatory profile of cells from an OA joint. We further report on the in vivo survival and engraftment of N-TEC in ectopic mouse models reproducing a human osteochondral OA tissue environment , as well as in sheep articular cartilage defects, ‘chronified’ to mimic degenerative settings. Finally, we tested clinically the implantion of autologous N-TEC in two patients with advanced OA (Kellgren and Lawrence grade 3 and 4), who were otherwise considered for unicondylar knee arthroplasty. 14 months after surgery, patients reported reduced pain as well as improved joint function and life quality. In addition, a radiologically observed increase in joint space suggested a beneficial disease modifying effect of the treatment. A phase II clinical trial is now required to assess efficacy in a larger cohort of OA patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003874","title":"RNA-seq as a global measure of the similarity between human pluripotent stem cell and fetal liver derived B cell hierarchies","description":null,"abstract":"Evidence suggests childhood acute lymphoblastic leukemia (cALL) arises in early human development. Existing models of pre-leukemic initiation using the ETV6-RUNX1 fusion do not recapitulate human disease, highlighting the need for a developmentally relevant human model system. A human pluripotent stem cell (hPSC) model genome was engineered to express ETV6-RUNX1 from the endogenous ETV6 promoter. RNA-seq data from sorted hematopoietic progenitors identified according to surface markers.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003875","title":"SG10K_Pilot - Large-scale whole-genome sequencing of three diverse Asian populations in Singapore","description":"Underrepresentation of Asian genomes has hindered population and medical genetics research on Asians, leading to population disparities in precision medicine. By whole-genome sequencing of 4,810 Singapore Chinese, Malays, and Indians, we found 98.3 million SNPs and small insertions/deletions, over half of which are novel. Population structure analysis demonstrated great representation of Asian genetic diversity by three ethnicities in Singapore, and revealed a Malay-related novel ancestry component. Furthermore, demographic inference suggested that Malays split from Chinese ~24,800 years ago, and experienced significant admixture with East Asians ~1,700 years ago, coinciding with the Austronesian expansion. Additionally, we identified 20 candidate loci for natural selection, among which 14 harbored robust associations with complex traits and diseases. Finally, we showed that our data can substantially improve genotype imputation in diverse Asian and Oceanian populations. These results highlight the value of our data as a resource to empower human genetics discovery across broad geographic regions.","abstract":"Underrepresentation of Asian genomes has hindered population and medical genetics research on Asians, leading to population disparities in precision medicine. By whole-genome sequencing of 4,810 Singapore Chinese, Malays, and Indians, we found 98.3 million SNPs and small insertions/deletions, over half of which are novel. Population structure analysis demonstrated great representation of Asian genetic diversity by three ethnicities in Singapore, and revealed a Malay-related novel ancestry component. Furthermore, demographic inference suggested that Malays split from Chinese ~24,800 years ago, and experienced significant admixture with East Asians ~1,700 years ago, coinciding with the Austronesian expansion. Additionally, we identified 20 candidate loci for natural selection, among which 14 harbored robust associations with complex traits and diseases. Finally, we showed that our data can substantially improve genotype imputation in diverse Asian and Oceanian populations. These results highlight the value of our data as a resource to empower human genetics discovery across broad geographic regions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-18T15:38:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003876","title":"Whole Genome Sequencing Reveals Potential Therapeutic Strategy for Monomorphic Epitheliotropic Intestinal T-cell Lymphoma","description":"Whole Genome Sequencing Reveals Potential Therapeutic Strategy for Monomorphic Epitheliotropic Intestinal T-cell Lymphoma","abstract":"Whole Genome Sequencing Reveals Potential Therapeutic Strategy for Monomorphic Epitheliotropic Intestinal T-cell Lymphoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-20T04:58:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003877","title":"Sphere-forming culture for expanding genetically-distinct patient-derived glioma stem cells by cellular growth rate screening","description":"Background: Diffusely infiltrating gliomas (DIGs) with extreme heterogeneity should be investigated for revealing tumor progression from lower-grade glioma to glioblastoma and customizing therapies. To assist the investigation of DIGs, advanced culture conditions are needed to establish personalized preclinical tools using patient-derived glioma stem cells (GSCs).Methods: We constructed a cellular growth rate screening platform called ‘GFSCAN’, which contains 132 different oncogenic growth factor combinations in serum-free neurobasal media. Seventy-two patient-derived GSCs were examined by GFSCAN, and their genomic profiles were also obtained. GFSCAN resulted in cell growth index to represent the cellular growth rate for each culture condition for each GSC.Results: Cell growth indexes generated by GFSCAN revealed that GSCs were clustered according to EGF and basic FGF (E&amp;F) dependency. IDH1-wild-type GSCs showed higher E&amp;F dependencies than IDH1-mutant GSCs, but mesenchymal IDH1-wild-type GSCs were relatively less dependent on E&amp;F. Therefore, we determined the improved in vitro cultivation conditions of E&amp;F independent GSCs based on their genomic and molecular characteristics, including IDH1 mutation, 1p/19q codeletion, ATRX alterations, and transcriptional subtype.Conclusions: We have identified the most optimal culture condition according to the genetic characteristics of GSCs through novel GFSCAN approach.","abstract":"Background: Diffusely infiltrating gliomas (DIGs) with extreme heterogeneity should be investigated for revealing tumor progression from lower-grade glioma to glioblastoma and customizing therapies. To assist the investigation of DIGs, advanced culture conditions are needed to establish personalized preclinical tools using patient-derived glioma stem cells (GSCs).Methods: We constructed a cellular growth rate screening platform called ‘GFSCAN’, which contains 132 different oncogenic growth factor combinations in serum-free neurobasal media. Seventy-two patient-derived GSCs were examined by GFSCAN, and their genomic profiles were also obtained. GFSCAN resulted in cell growth index to represent the cellular growth rate for each culture condition for each GSC.Results: Cell growth indexes generated by GFSCAN revealed that GSCs were clustered according to EGF and basic FGF (E&amp;F) dependency. IDH1-wild-type GSCs showed higher E&amp;F dependencies than IDH1-mutant GSCs, but mesenchymal IDH1-wild-type GSCs were relatively less dependent on E&amp;F. Therefore, we determined the improved in vitro cultivation conditions of E&amp;F independent GSCs based on their genomic and molecular characteristics, including IDH1 mutation, 1p/19q codeletion, ATRX alterations, and transcriptional subtype.Conclusions: We have identified the most optimal culture condition according to the genetic characteristics of GSCs through novel GFSCAN approach.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003878","title":"Predicting ultra-high risk multiple myeloma by molecular profiling","description":"Gene expression profiling of 329 NDMM patients from the NCRI Myeloma XI using SKY92 MMProfiler (SkylineDx, The Netherlands) expression arrays.","abstract":"Gene expression profiling of 329 NDMM patients from the NCRI Myeloma XI using SKY92 MMProfiler (SkylineDx, The Netherlands) expression arrays.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003879","title":"ICN1-induced human T-ALLs","description":"Exome sequencing was performed on 4 independent human T-cell acute lymphoblastic leukemia samples arising in immunodeficient mice after transplantation of 3 donors-pooled hematopoietic stem cell progenitors transduced with an oncogenic NOTCH1 mutant.","abstract":"Exome sequencing was performed on 4 independent human T-cell acute lymphoblastic leukemia samples arising in immunodeficient mice after transplantation of 3 donors-pooled hematopoietic stem cell progenitors transduced with an oncogenic NOTCH1 mutant.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003880","title":"Pilot_Sequencing_of_Multiplexed_gRNA_Library","description":"We have developed a CRISPR/Cas9 platform for multiplexed analysis of gene essentiality in human cells.\nThis is a pilot experiment aimed to verify that our current protocol can be scaled up effectively, for future upscaling.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We have developed a minimised guide RNA library that allows a 3-fold reduction in size and cost of genome-wide CRISPR-Cas9 screen, within the framework of a larger project aimed to understand to which extent gene essentiality varies in healthy humans. This new minimised libraries required the development of a new protocol for the sequencing of the amplicon from genomic DNA. The aim of this pilot is to verify that the new protocol performs well and is scalable.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003881","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___GI___LYNCH___WES","description":"Somatic mutations (burdens and signatures) and clonal dynamics in normal human tissues from the gastrointestinal tract of individuals with tumour predisposition syndromes and DNA damage repair defects.","abstract":"he aim of this project is to investiagte somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the study of normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to identify and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003882","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___GI___LYNCH___WGS","description":"Somatic mutations (burdens and signatures) and clonal dynamics in normal human tissues from the gastrointestinal tract of individuals with tumour predisposition syndromes and DNA damage repair defects.","abstract":"The aim of this project is to investiagte somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the studyof normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to idnetifiy and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-20T16:14:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003883","title":"Systematic comparative analysis of single-nucleotide variants detection methods from single-cell RNA sequencing data","description":"Systematic interrogation of single nucleotide variations (SNVs) is one of the most promising approaches to delineate the cellular heterogeneity and phylogenetic relationships at the single cell level. While SNV detection from abundant single cell RNA sequencing (scRNA-seq) data is applicable and cost-effective in identifying expressed variants, inferring sub-clones, and deciphering genotype-phenotype linkages, there is a lack of computational methods specifically developed for SNV calling in scRNA-seq. Although variant callers for bulk RNA-seq have been sporadically used in scRNA-seq, the performances of different tools have not been assessed. Here, we performed a systematic comparison of seven tools including SAMtools, the GATK pipeline, CTAT, FreeBayes, MuTect2, Strelka2 and VarScan2, using both simulation and scRNA-seq datasets, and identified multiple elements influencing their performance. Our study provided the first benchmarking to evaluate the performances of different SNV detection tools for scRNA-seq data.","abstract":"Systematic interrogation of single nucleotide variations (SNVs) is one of the most promising approaches to delineate the cellular heterogeneity and phylogenetic relationships at the single cell level. While SNV detection from abundant single cell RNA sequencing (scRNA-seq) data is applicable and cost-effective in identifying expressed variants, inferring sub-clones, and deciphering genotype-phenotype linkages, there is a lack of computational methods specifically developed for SNV calling in scRNA-seq. Although variant callers for bulk RNA-seq have been sporadically used in scRNA-seq, the performances of different tools have not been assessed. Here, we performed a systematic comparison of seven tools including SAMtools, the GATK pipeline, CTAT, FreeBayes, MuTect2, Strelka2 and VarScan2, using both simulation and scRNA-seq datasets, and identified multiple elements influencing their performance. Our study provided the first benchmarking to evaluate the performances of different SNV detection tools for scRNA-seq data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-23T08:37:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003884","title":"Cutaneous T-cell lymphoma","description":"Exome sequencing was performed on 4 cell subtypes isolated from the blood of a cutaneous T-cell lymphoma patient: normal granulocytes (AD6133), leukemic CD4+ blasts (AD6134), and 2 phenotypically different populations of CD4+ T lymphocytes (AD6135 and AD6136).","abstract":"Exome sequencing was performed on 4 cell subtypes isolated from the blood of a cutaneous T-cell lymphoma patient: normal granulocytes (AD6133), leukemic CD4+ blasts (AD6134), and 2 phenotypically different populations of CD4+ T lymphocytes (AD6135 and AD6136).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003885","title":"HCA_Gonads_Adult_MRC_RNA","description":"Sexual reproduction depends on the fusion of gametes (sperm and eggs) during fertilisation followed by implantation of the resulting embryo in the lining of the womb (the endometrium). Gametes halve their genome in preparation for fertilisation during a specialized cell division known as meiosis. The process by which meiosis is co-ordinated with gamete formation in females is poorly understood, principally because it commences in utero and is not completed until decades later when the mature egg is ovulated and fertilised. \nTo address the many gaps in our knowledge of the development of the germline and reproductive system in humans, we propose to generate a comprehensive cell atlas of adult gonads. We will combine gene-expression profiling at the single-cell level and atac-seq with new methods of gene-expression detection directly on the tissue to study the cellular environment at an unprecedented resolution and coverage. Information about the expression of the myriad of cells and cell states in reproductive cells will greatly advance our understanding of the development of the female reproductive system and the emergence and maintenance of the female germline in humans. \n\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Sexual reproduction depends on the fusion of gametes (sperm and eggs) during fertilisation followed by implantation of the resulting embryo in the lining of the womb (the endometrium). Gametes halve their genome in preparation for fertilisation during a specialized cell division known as meiosis. The process by which meiosis is co-ordinated with gamete formation in females is poorly understood, principally because it commences in utero and is not completed until decades later when the mature egg is ovulated and fertilised. \nTo address the many gaps in our knowledge of the development of the germline and reproductive system in humans, we propose to generate a comprehensive cell atlas of adult gonads. We will combine gene-expression profiling at the single-cell level and atac-seq with new methods of gene-expression detection directly on the tissue to study the cellular environment at an unprecedented resolution and coverage. Information about the expression of the myriad of cells and cell states in reproductive cells will greatly advance our understanding of the development of the female reproductive system and the emergence and maintenance of the female germline in humans. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003886","title":"Immunopeptidomics of colorectal cancer organoids reveals a sparse HLA class I neoantigen landscape and no increase in neoantigens with interferon or MEK-inhibitor treatment","description":null,"abstract":"Patient derived organoids (PDOs) can be established from colorectal cancers (CRCs) as in vitro models to interrogate cancer biology and its clinical relevance. We applied mass spectrometry (MS) immunopeptidomics to investigate neoantigen presentation and whether this can be augmented through interferon gamma (IFN) or MEK-inhibitor treatment.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-23T16:34:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003887","title":"Immuno-genomic landscape of osteosarcoma","description":"Osteosarcoma is an orphan disease affecting children and young adults that has seen little to no progress in survival outcomes for &gt;30 years. Despite having heavily rearranged genomes, to date, clinical trials with immunotherapy have shown no benefit for patients with osteosarcoma. In this study, we conducted the first multi-platform immune profiling (whole genome, transcriptome, T-cell receptor sequencing, immunohistochemistry and reverse phase protein array) on every available pediatric and adult osteosarcoma patients from our institution (N = 48) with the goal of describing immune features that may contribute to immunotherapy resistance.","abstract":"Osteosarcoma is an orphan disease affecting children and young adults that has seen little to no progress in survival outcomes for &gt;30 years. Despite having heavily rearranged genomes, to date, clinical trials with immunotherapy have shown no benefit for patients with osteosarcoma. In this study, we conducted the first multi-platform immune profiling (whole genome, transcriptome, T-cell receptor sequencing, immunohistochemistry and reverse phase protein array) on every available pediatric and adult osteosarcoma patients from our institution (N = 48) with the goal of describing immune features that may contribute to immunotherapy resistance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-23T14:55:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003888","title":"RNAseq_of_Human_Organoid_Lines","description":"The study will use RNAseq to aid in benchmarking different culture conditions  in a set of genetically annotated human organoid lines. The data will be used to assess whether there is any clonal differences introduced when culturing these lines in different conditions.","abstract":"The study will use RNAseq to aid in benchmarking different culture conditions  in a set of genetically annotated human organoid lines. The data will be used to assess whether there is any clonal differences introduced when culturing these lines in different conditions.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-23T16:58:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003889","title":"Studying the single cell characteristics of pancreatic cancer","description":"Pancreatic cancer is a dangerous malignancy in the pancreas. In this study we use single-cell RNA sequencing technique to help understand the transcriptome characteristics of pancreatic tumor cells. This study help understands the complex microenvironment of pancreatic tumors and will likely to benefit clinical research of pancreatic cancer treatments.","abstract":"Pancreatic cancer is a dangerous malignancy in the pancreas. In this study we use single-cell RNA sequencing technique to help understand the transcriptome characteristics of pancreatic tumor cells. This study help understands the complex microenvironment of pancreatic tumors and will likely to benefit clinical research of pancreatic cancer treatments.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-24T02:14:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003890","title":"Oesophageal_Adenocarcinoma_Organoid_ATAC","description":"ATAC Sequencing of 5 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical rescetion of the tumour. All model derivations took place with the CGaP facility in Sanger.  This ATAC data will be combined with other sequencing data in order to generate","abstract":"here is complex interplay between underlying genetic sequence and epigenetic factors, however this interplay is still illusive. Massively reconstructed cancer genomes can be used in order to better understand this relationship. Six oesophageal adenocarcinoma organoids will be sequenced using long read sequencing technologies and will be profiled for a range of epigenetic marks. Combination of genetic and epigenetic data will allow the thorough characterisation of reference cancer genomes and will provide novel insights into mechanisms of gene regulation.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-25T14:35:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003891","title":"Molecular profiling of blastic plasmacytoid dendritic cell neoplasm (BPDCN) as compared to acute myeloid leukemia (AML)","description":null,"abstract":"Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, male-predominant myeloid malignancy that is characterized by the malignant proliferation of precursor plasmacytoid dendritic cells (pDCs) with morphologic and molecular similarities to acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in its presentation within the bone marrow and peripheral blood. To identify disease-specific molecular features of BPDCN, we profiled bone marrow, peripheral blood and serum samples from primary patient samples using an in-house hematologic malignancy panel (“T300” panel), transcriptome microarray, and serum multiplex immunoassays and compared results to a cohort of AML patients.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003892","title":"Multimodal Genomic Features Predict Outcome of Immune Checkpoint Blockade in Non-small Cell Lung Cancer","description":"Despite progress in immunotherapy, identifying patients that respond has remained a challenge. Through analysis of whole-exome and targeted sequence data from 5,449 tumors, we found a significant correlation between tumor mutation burden (TMB) and tumor purity, suggesting that low tumor purity tumors are likely to have inaccurate TMB estimates. We developed a new method to estimate a corrected TMB (cTMB) that was adjusted for tumor purity and more accurately predicted outcome to immune checkpoint blockade (ICB). To identify improved predictive markers together with cTMB, we performed whole-exome sequencing for 104 lung tumors treated with ICB. Through comprehensive analyses of sequence and structural alterations, we discovered a significant enrichment in activating mutations in receptor tyrosine kinase (RTK) genes in non-responding tumors in three immunotherapy-treated cohorts. An integrated multivariable model incorporating cTMB, RTK mutations, smoking-related mutational signature, and HLA status provided an improved predictor of response to immunotherapy that was independently validated.","abstract":"Despite progress in immunotherapy, identifying patients that respond has remained a challenge. Through analysis of whole-exome and targeted sequence data from 5,449 tumors, we found a significant correlation between tumor mutation burden (TMB) and tumor purity, suggesting that low tumor purity tumors are likely to have inaccurate TMB estimates. We developed a new method to estimate a corrected TMB (cTMB) that was adjusted for tumor purity and more accurately predicted outcome to immune checkpoint blockade (ICB). To identify improved predictive markers together with cTMB, we performed whole-exome sequencing for 104 lung tumors treated with ICB. Through comprehensive analyses of sequence and structural alterations, we discovered a significant enrichment in activating mutations in receptor tyrosine kinase (RTK) genes in non-responding tumors in three immunotherapy-treated cohorts. An integrated multivariable model incorporating cTMB, RTK mutations, smoking-related mutational signature, and HLA status provided an improved predictor of response to immunotherapy that was independently validated.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-26T11:48:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003893","title":"Transcriptome sequencing of gingivo-buccal oral squamous cell carcinoma for integrative analysis: alterations in expression of genes attributable to methylation changes","description":"Gingivo-buccal oral squamous cell carcinoma (OSCC-GB) is the most common cancer among men in India and is associated with high mortality. Although OSCC-GB is known to be quite different from tongue cancer in its genomic presentation and its clinical behavior, it is treated identically as tongue cancer. Predictive markers of prognosis and therapy that are specific to OSCC-GB are, therefore, required. To achieve this, we have carried out transcriptome (n=72) profiling of paired tumor-normal tissues collected from OSCC-GB patients from India.\n\tRNA sequencing was performed on tumor and paired adjacent normal samples from 72 OSCC-GB patients. From each patient, total RNA was extracted from tumor and normal tissue samples using AllPrep DNA/RNA Mini Kit (QIAGEN). The quality and concentration of isolated total RNA were checked using Agilent 2100 Bioanalyzer and NanoDrop 2000 (Thermo Fisher Scientific). The OD260/OD280 ratio was ≥ 2 and RNA Integrity Number (RIN) was ≥ 7.0 for all sequenced samples. Ribosomal RNA (rRNA) was removed from the RNA samples, using Ribo-Zero Magnetic Kit (Epicentre). Sequencing libraries were prepared from rRNA depleted samples using TrueSeq RNA Sample Preparation Kit (Illumina). Each triplex cDNA library pool was sequenced as 100bp paired-end on HiSeq-2000 or HiSeq-2500 (Illumina). Protocols suggested by the manufacturers were used for all assays.","abstract":"Gingivo-buccal oral squamous cell carcinoma (OSCC-GB) is the most common cancer among men in India and is associated with high mortality. Although OSCC-GB is known to be quite different from tongue cancer in its genomic presentation and its clinical behavior, it is treated identically as tongue cancer. Predictive markers of prognosis and therapy that are specific to OSCC-GB are, therefore, required. To achieve this, we have carried out transcriptome (n=72) profiling of paired tumor-normal tissues collected from OSCC-GB patients from India.\n\tRNA sequencing was performed on tumor and paired adjacent normal samples from 72 OSCC-GB patients. From each patient, total RNA was extracted from tumor and normal tissue samples using AllPrep DNA/RNA Mini Kit (QIAGEN). The quality and concentration of isolated total RNA were checked using Agilent 2100 Bioanalyzer and NanoDrop 2000 (Thermo Fisher Scientific). The OD260/OD280 ratio was ≥ 2 and RNA Integrity Number (RIN) was ≥ 7.0 for all sequenced samples. Ribosomal RNA (rRNA) was removed from the RNA samples, using Ribo-Zero Magnetic Kit (Epicentre). Sequencing libraries were prepared from rRNA depleted samples using TrueSeq RNA Sample Preparation Kit (Illumina). Each triplex cDNA library pool was sequenced as 100bp paired-end on HiSeq-2000 or HiSeq-2500 (Illumina). Protocols suggested by the manufacturers were used for all assays.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-26T12:09:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003894","title":"Control iPSC lines with clinically annotated genetic variants for versatile multi-lineage differentiation (2nd part)","description":null,"abstract":"Induced Pluripotent Stem Cells (iPSC) derived from healthy individuals are important controls for disease modeling studies. To create a resource of genetically annotated iPSC, we reprogrammed footprint-free lines from four volunteers in the Personal Genome Project Canada (PGPC). Multilineage directed differentiation efficiently produced functional cortical neurons, cardiomyocytes and hepatocytes. Pilot users further demonstrated line versatility by generating kidney organoids, T-cells and sensory neurons. A frameshift knockout was introduced into MYBPC3 and these cardiomyocytes exhibited a hypertrophic phenotype as expected. WGS annotation of PGPC lines revealed on average 20 coding variants. Importantly, nearly all annotated PGPC and HipSci lines harboured at least one pre-existing or acquired variant with cardiac, neurological or other disease associations. Overall, PGPC lines were efficiently differentiated by multiple users into cell types found in six tissues for disease modelling, and clinical annotation highlighted variant-preferred lines for use as unaffected controls in specific disease settings.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003895","title":"Whole genome and whole transcriptome sequencing of patients diagnosed with angiosarcoma.","description":"Angiosarcomas are rare, clinically-aggressive tumors with a predilection for the elderly and immunosuppressed, which has incited suspicion of an oncogenic virus. We studied the metagenomic landscape of angiosarcomas and identified reads mapping to human herpesvirus-7 (HHV-7). Overall, HHV-7 was present in two-thirds of angiosarcomas, particularly in cases with low tumor mutation burden and lacking signatures of ultraviolet-induced DNA damage. Transcriptomic profiling revealed the enrichment of tumor inflammation signatures in HHV7-positive angiosarcomas. In conclusion, we identified a distinct “inflammatory” subtype of angiosarcoma associated with HHV-7.","abstract":"Angiosarcomas are rare, clinically-aggressive tumors with a predilection for the elderly and immunosuppressed, which has incited suspicion of an oncogenic virus. We studied the metagenomic landscape of angiosarcomas and identified reads mapping to human herpesvirus-7 (HHV-7). Overall, HHV-7 was present in two-thirds of angiosarcomas, particularly in cases with low tumor mutation burden and lacking signatures of ultraviolet-induced DNA damage. Transcriptomic profiling revealed the enrichment of tumor inflammation signatures in HHV7-positive angiosarcomas. In conclusion, we identified a distinct “inflammatory” subtype of angiosarcoma associated with HHV-7.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-27T10:02:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003896","title":"Epigenome wide DNA methylation assay of gingivo-buccal oral squamous cell carcinoma using single base resolution high throughput array","description":"Gingivo-buccal oral squamous cell carcinoma (OSCC-GB) is the most common cancer among men in India and is associated with high mortality. Although OSCC-GB is known to be quite different from tongue cancer in its genomic presentation and its clinical behavior, it is treated identically as tongue cancer. Predictive markers of prognosis and therapy that are specific to OSCC-GB are, therefore, required. To achieve this, we have carried out epigenomic (n=87) profiling of paired tumor-normal tissues collected from OSCC-GB patients from India and genome-wide DNA methylation assays were performed. DNA was isolated using DNeasy Blood and Tissue Kit (Qiagen). The purity and concentration was estimated using NanoDrop 2000 (Thermo Fisher Scientific). Approximately 500 ng genomic DNA from each sample was used for sodium bisulfite conversion using the EZ DNA methylation Gold Kit (Zymo Research, USA). Genome-wide DNA methylation was assayed using iScan (Illumina), for paired tumour and adjacent normal samples of 25 patients using the Infinium Human Methylation450 BeadChip and of 62 patients using the Infinium MethylationEPIC BeadChip.","abstract":"Gingivo-buccal oral squamous cell carcinoma (OSCC-GB) is the most common cancer among men in India and is associated with high mortality. Although OSCC-GB is known to be quite different from tongue cancer in its genomic presentation and its clinical behavior, it is treated identically as tongue cancer. Predictive markers of prognosis and therapy that are specific to OSCC-GB are, therefore, required. To achieve this, we have carried out epigenomic (n=87) profiling of paired tumor-normal tissues collected from OSCC-GB patients from India and genome-wide DNA methylation assays were performed. DNA was isolated using DNeasy Blood and Tissue Kit (Qiagen). The purity and concentration was estimated using NanoDrop 2000 (Thermo Fisher Scientific). Approximately 500 ng genomic DNA from each sample was used for sodium bisulfite conversion using the EZ DNA methylation Gold Kit (Zymo Research, USA). Genome-wide DNA methylation was assayed using iScan (Illumina), for paired tumour and adjacent normal samples of 25 patients using the Infinium Human Methylation450 BeadChip and of 62 patients using the Infinium MethylationEPIC BeadChip.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-27T12:21:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003897","title":"Single-cell T-cell receptor sequencing of intraepithelial gammadelta T-cells in celiac disease","description":"Single-cell paired TCR sequencing of intraepithelial γδ T-cells in gluten-free diet treated and untreated celiac disease patients and in controls. (Paired end, amplicon sequencing).","abstract":"Single-cell paired TCR sequencing of intraepithelial γδ T-cells in gluten-free diet treated and untreated celiac disease patients and in controls. (Paired end, amplicon sequencing).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-27T12:44:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003898","title":"WES of 2 osteosarcoma samples and the corresponding primary cell lines","description":"Osteosarcoma","abstract":"Osteosarcoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003899","title":"Identification of hypermutation and defective mismatch repair in ctDNA from metastatic prostate cancer","description":"DNA mismatch repair defects (MMRd) and tumor hypermutation are rare and under-characterized in metastatic prostate cancer. Furthermore, since hypermutated MMRd prostate cancers can respond to immune checkpoint inhibitors, there is an urgent need for practical detection tools. We analyzed cell-free DNA targeted sequencing data from 434 metastatic prostate cancer patients with circulating tumor DNA (ctDNA) purity above 2%. Samples with somatic hypermutation were subjected to 150x whole exome sequencing. These data allowed us to interrogate the salient genomic properties of this rare prostate cancer subtype and correlate findings with patient clinical outcomes.","abstract":"DNA mismatch repair defects (MMRd) and tumor hypermutation are rare and under-characterized in metastatic prostate cancer. Furthermore, since hypermutated MMRd prostate cancers can respond to immune checkpoint inhibitors, there is an urgent need for practical detection tools. We analyzed cell-free DNA targeted sequencing data from 434 metastatic prostate cancer patients with circulating tumor DNA (ctDNA) purity above 2%. Samples with somatic hypermutation were subjected to 150x whole exome sequencing. These data allowed us to interrogate the salient genomic properties of this rare prostate cancer subtype and correlate findings with patient clinical outcomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-27T14:37:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003900","title":"Integrative analysis of pediatric cancer","description":null,"abstract":"This study covers a variety of pediatric cancer diagnoses, profiled using whole-genome sequencing and RNAseq.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003901","title":"Screening of 2.5 million SNPs in 142 samples from the western Mediterranean area","description":"The analysis of 2.5 million SNPs in 142 samples from the western Mediterranean area, including southern Spain, Andalusia (Huelva: 35 samples, Granada: 35), southern Portugal (36 samples) and Moroccan Berbers (Asni: 15, Bouhria: 12 and Figuig: 9).","abstract":"The analysis of 2.5 million SNPs in 142 samples from the western Mediterranean area, including southern Spain, Andalusia (Huelva: 35 samples, Granada: 35), southern Portugal (36 samples) and Moroccan Berbers (Asni: 15, Bouhria: 12 and Figuig: 9).","study_type":"Other","pubmed_ids":[31816048],"external_links":null,"is_released":true,"released_date":"2019-09-29T22:17:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003917","title":"Human Biofluid RNA Atlas Project - raw data","description":null,"abstract":"Extracellular RNAs (exRNAs) present in biofluids have emerged as potential biomarkers in health and disease. Currently, most efforts concentrate on plasma or serum. However, depending on the disease, other biofluids may contain more informative RNA molecules. Here, we present the mRNA, circular RNA and small RNA transcriptomes of a comprehensive collection of 20 human biofluids. By means of synthetic RNA spike-in controls, we compared RNA content across biofluids, revealing a more than 1000-fold difference in RNA concentration among the fluids. Of interest, circular RNAs are significantly enriched in biofluids compared to tissue samples. Further, each biofluid is characterized by an enrichment of specific RNA markers, reflecting specific tissue and cell type contributions. To verify the biomarker potential in these biofluids, four validation cohorts representing a broad spectrum of diseases were profiled, revealing numerous differential RNAs between case and control subjects. Taken together, our results may guide the selection of the most relevant biofluid to monitor particular disease types and serves as a valuable resource for future biomarker studies.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-30T16:42:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003922","title":"Meisal temporal lobe epilepsy sequencing study","description":"Our understanding of mesial temporal lobe epilepsy (MTLE) is one of the most common forms of drug-resistant epilepsy in humans. Using RNA- and small RNA-sequencing in parallel, we explored differentially expressed genes in the hippocampus and cortex of MTLE patients who had undergone surgical resection and non-epileptic controls. We found significant enrichment for astrocytic and microglial genes amongst up-regulated genes and down-regulation of neuron-specific genes in the hippocampus of MTLE patients. The transcriptome profile of the small RNAs reflected disease state more robustly than mRNAs, even across brain regions which show very little pathology.","abstract":"Our understanding of mesial temporal lobe epilepsy (MTLE) is one of the most common forms of drug-resistant epilepsy in humans. Using RNA- and small RNA-sequencing in parallel, we explored differentially expressed genes in the hippocampus and cortex of MTLE patients who had undergone surgical resection and non-epileptic controls. We found significant enrichment for astrocytic and microglial genes amongst up-regulated genes and down-regulation of neuron-specific genes in the hippocampus of MTLE patients. The transcriptome profile of the small RNAs reflected disease state more robustly than mRNAs, even across brain regions which show very little pathology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-09-30T16:35:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003923","title":"WES of 2 human osteosarcoma and corresponding cell lines","description":"Progress in the systemic control of osteosarcoma has been limited over the past decades thus indicating the urgent clinical need for the development of novel treatment strategies. Therefore, we have recently developed new preclinical models to study promising novel agents for the treatment of pediatric osteosarcoma. The checkpoint kinase (chk) inhibitor prexasertib (LY2606368) and its salt form (LSN2940930) have recently been shown to be active in adult and pediatric malignancies, including sarcoma. We have now tested the potency of prexasertib in clonogenic survival assays in two new lines of primary patient-derived osteosarcoma cells and in two established osteosarcoma cell lines as a single agent and in combination with cisplatin and the poly ADP-ribose polymerase (PARP) inhibitor talazoparib. Prexasertib alone results in strongly reduced clonogenic survival at low nanomolar concentrations and acts by affecting cell cycle progression, induction of apoptosis and induction of double-stranded DNA breakage at concentrations that are well below clinically tolerable and safe plasma concentrations. In combination with cisplatin and talazoparib, prexasertib acts in a synergistic fashion. Chk1 inhibition by prexasertib and its combination with the DNA damaging agent cisplatin and the PARP-inhibitor talazoparib thus emerges as a potential new treatment option for pediatric osteosarcoma which will now have to be tested in preclinical primary patient derived in vivo models and clinical studies.","abstract":"Progress in the systemic control of osteosarcoma has been limited over the past decades thus indicating the urgent clinical need for the development of novel treatment strategies. Therefore, we have recently developed new preclinical models to study promising novel agents for the treatment of pediatric osteosarcoma. The checkpoint kinase (chk) inhibitor prexasertib (LY2606368) and its salt form (LSN2940930) have recently been shown to be active in adult and pediatric malignancies, including sarcoma. We have now tested the potency of prexasertib in clonogenic survival assays in two new lines of primary patient-derived osteosarcoma cells and in two established osteosarcoma cell lines as a single agent and in combination with cisplatin and the poly ADP-ribose polymerase (PARP) inhibitor talazoparib. Prexasertib alone results in strongly reduced clonogenic survival at low nanomolar concentrations and acts by affecting cell cycle progression, induction of apoptosis and induction of double-stranded DNA breakage at concentrations that are well below clinically tolerable and safe plasma concentrations. In combination with cisplatin and talazoparib, prexasertib acts in a synergistic fashion. Chk1 inhibition by prexasertib and its combination with the DNA damaging agent cisplatin and the PARP-inhibitor talazoparib thus emerges as a potential new treatment option for pediatric osteosarcoma which will now have to be tested in preclinical primary patient derived in vivo models and clinical studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-01T11:20:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003924","title":"UK Biobank whole cohort genetic data (~500k participants)","description":"UK Biobank whole cohort genetic data (~500k participants)","abstract":"UK Biobank whole cohort genetic data (~500k participants)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001003925","title":"DNA and RNA sequencing of relapsing pre-B ALL with Multi-timepoint Samples","description":null,"abstract":"B-cell acute lymphoblastic leukemia (B-ALL) is the most common cancer observed in children. One of the most critical modern risk stratifications involves molecular profiling including structure variants, cytogenetic abnormalities, and point mutations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003926","title":"WGS Multiple Myeloma XI trial","description":"Most patients with multiple myeloma (MM) die from progressive disease after relapse. To advance our understanding of MM evolution mechanisms, we performed whole-genome sequencing of 80 tumour-normal newly diagnosed pairs and 25 matched relapse tumours from the Myeloma XI trial.  We identify multiple events as important for survival and therapy-resistance at relapse including driver point mutations (e.g. SYNE1, MTCL1, TET2), translocations (MAP3K14), and increased genomic instability (e.g. 13q and 17p deletions). MM relapse has higher mutational burden, associated with increased AID/APOBEC activity and DNA repair deficiency. In addition, we identified three major patterns of clonal evolution. Our data show that MM relapse is associated with acquisition of new mutations and clonal selection, which may be shaped in part by patient therapy.","abstract":"Most patients with multiple myeloma (MM) die from progressive disease after relapse. To advance our understanding of MM evolution mechanisms, we performed whole-genome sequencing of 80 tumour-normal newly diagnosed pairs and 25 matched relapse tumours from the Myeloma XI trial.  We identify multiple events as important for survival and therapy-resistance at relapse including driver point mutations (e.g. SYNE1, MTCL1, TET2), translocations (MAP3K14), and increased genomic instability (e.g. 13q and 17p deletions). MM relapse has higher mutational burden, associated with increased AID/APOBEC activity and DNA repair deficiency. In addition, we identified three major patterns of clonal evolution. Our data show that MM relapse is associated with acquisition of new mutations and clonal selection, which may be shaped in part by patient therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003927","title":"RNA-seq Multiple Myeloma XI trial","description":"Most patients with multiple myeloma (MM) die from progressive disease after relapse. To advance our understanding of MM evolution mechanisms, we performed whole-genome sequencing of 80 tumour-normal newly diagnosed pairs and 25 matched relapse tumours from the Myeloma XI trial.  We identify multiple events as important for survival and therapy-resistance at relapse including driver point mutations (e.g. SYNE1, MTCL1, TET2), translocations (MAP3K14), and increased genomic instability (e.g. 13q and 17p deletions). MM relapse has higher mutational burden, associated with increased AID/APOBEC activity and DNA repair deficiency. In addition, we identified three major patterns of clonal evolution. Our data show that MM relapse is associated with acquisition of new mutations and clonal selection, which may be shaped in part by patient therapy.","abstract":"Most patients with multiple myeloma (MM) die from progressive disease after relapse. To advance our understanding of MM evolution mechanisms, we performed whole-genome sequencing of 80 tumour-normal newly diagnosed pairs and 25 matched relapse tumours from the Myeloma XI trial.  We identify multiple events as important for survival and therapy-resistance at relapse including driver point mutations (e.g. SYNE1, MTCL1, TET2), translocations (MAP3K14), and increased genomic instability (e.g. 13q and 17p deletions). MM relapse has higher mutational burden, associated with increased AID/APOBEC activity and DNA repair deficiency. In addition, we identified three major patterns of clonal evolution. Our data show that MM relapse is associated with acquisition of new mutations and clonal selection, which may be shaped in part by patient therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003928","title":"Cistrome-partitioning reveals convergence of somatic mutations and risk-variants on master transcription regulators in primary prostate tumors","description":"Thousands of noncoding somatic Single Nucleotide Variants (SNVs) of unknown\nfunction are reported in tumors. Partitioning the genome according to cistromes,\nreveals the enrichment of somatic SNVs in prostate tumors as opposed to adjacent\nnormal tissue cistromes of master transcription regulators, including AR, FOXA1 and\nHOXB13. This parallels enrichment of prostate cancer genetic predispositions over\nthese transcription regulators’ tumor cistromes, exemplified at the 8q24 locus harboring\nboth risk-variants and somatic SNVs in cis-regulatory elements, upregulating MYC\nexpression and altering the binding of transcription regulators to DNA. However, Massively-Parallel Reporter Assays reveal that few SNVs can alter the transactivation\npotential of individual CREs. Instead, SNVs accumulate, similarly to inherited riskvariants,\nin cistromes of master transcription regulators required for prostate cancer\ndevelopment.\nDifficulties in inferring the biological significance of noncoding mutations have limited\ntheir inclusion in precision genomics medicine pipelines. Most attempts to delineate a\nrole for noncoding mutations relied on detecting evidence for positive selection within\nindividual CREs, such as reported for the TERT gene promoter. By considering the\nenrichment of noncoding mutations in cistromes as opposed to individual CREs, we\nreveal their specificity towards master transcription regulators that promote prostate\ncancer development, a feature shared with inherited risk-variants. Overall, our work\nprovides a blueprint for the functional interpretation of noncoding mutations in genomic\ntests relying on defining cis-regulatory units according to cistrome-partitioning to\nidentify cancer driver transcription regulators.","abstract":"Thousands of noncoding somatic Single Nucleotide Variants (SNVs) of unknown\nfunction are reported in tumors. Partitioning the genome according to cistromes,\nreveals the enrichment of somatic SNVs in prostate tumors as opposed to adjacent\nnormal tissue cistromes of master transcription regulators, including AR, FOXA1 and\nHOXB13. This parallels enrichment of prostate cancer genetic predispositions over\nthese transcription regulators’ tumor cistromes, exemplified at the 8q24 locus harboring\nboth risk-variants and somatic SNVs in cis-regulatory elements, upregulating MYC\nexpression and altering the binding of transcription regulators to DNA. However, Massively-Parallel Reporter Assays reveal that few SNVs can alter the transactivation\npotential of individual CREs. Instead, SNVs accumulate, similarly to inherited riskvariants,\nin cistromes of master transcription regulators required for prostate cancer\ndevelopment.\nDifficulties in inferring the biological significance of noncoding mutations have limited\ntheir inclusion in precision genomics medicine pipelines. Most attempts to delineate a\nrole for noncoding mutations relied on detecting evidence for positive selection within\nindividual CREs, such as reported for the TERT gene promoter. By considering the\nenrichment of noncoding mutations in cistromes as opposed to individual CREs, we\nreveal their specificity towards master transcription regulators that promote prostate\ncancer development, a feature shared with inherited risk-variants. Overall, our work\nprovides a blueprint for the functional interpretation of noncoding mutations in genomic\ntests relying on defining cis-regulatory units according to cistrome-partitioning to\nidentify cancer driver transcription regulators.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-02T13:36:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003929","title":"Cyprus_Samples_AML_TGS","description":"Sequencing of AML samples to identify mutations that can then be tracked on pre-AML DNA","abstract":"Sequencing of AML samples to identify mutations that can then be tracked on pre-AML DNA","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003930","title":"De_Novo_melanoma_predisposition___WES","description":"In this project we will sequence the germline exome of a patient who by the 4th decade had developed six primary melanomas. She had no prior family history of melanoma. To help identify mosaic variants we will also sequence the germline of the patient’s parents. To also try and identify somatically mutated genes we will sequence three of the patient’s tumours to compare them against her germline sample.","abstract":"In this project we will sequence the germline exome of a patient who by the 4th decade had developed six primary melanomas. She had no prior family history of melanoma. To help identify mosaic variants we will also sequence the germline of the patient’s parents. To also try and identify somatically mutated genes we will sequence three of the patient’s tumours to compare them against her germline sample.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003931","title":"Pan-neuroblastoma analysis reveals age- and signature-associated driver alterations","description":"Neuroblastoma is a pediatric malignancy with heterogeneous clinical outcomes depending on age and other factors. To better understand neuroblastoma pathogenesis, here we analyze whole-genome, whole-exome and/or transcriptome sequencing data from 702 neuroblastoma samples, half of which are new data. Over 95% of samples harbor at least one recurrent driver alteration and most aberrations, including MYCN, ATRX, and TERT alterations, differ in frequency by age. MYCN alterations occur at median 2.3 years of age, TERT at 3.8 years, and ATRX at 5.6 years, suggesting age-specific susceptibility to genetic alterations. Mutational signature analysis shows that reactive oxygen-species (ROS)-induced mutations are the most common cause of single nucleotide variant (SNV) drivers in neuroblastoma, including most ALK and Ras pathway SNVs.  ROS-induced mutagenesis is both an early event, as it causes truncal variants, and continuous as it also induces relapse-specific mutations. ROS-induced mutations are more abundant in neuroblastomas with MYCN amplification, 17q gains, and increased expression of mitochondrial ribosome genes. We observe recurrent FGFR1 N546K or internal tandem duplication variants in 6 patients and ALK N-terminal structural alterations in 5 samples, identifying additional patients amenable to precision therapy.","abstract":"Neuroblastoma is a pediatric malignancy with heterogeneous clinical outcomes depending on age and other factors. To better understand neuroblastoma pathogenesis, here we analyze whole-genome, whole-exome and/or transcriptome sequencing data from 702 neuroblastoma samples, half of which are new data. Over 95% of samples harbor at least one recurrent driver alteration and most aberrations, including MYCN, ATRX, and TERT alterations, differ in frequency by age. MYCN alterations occur at median 2.3 years of age, TERT at 3.8 years, and ATRX at 5.6 years, suggesting age-specific susceptibility to genetic alterations. Mutational signature analysis shows that reactive oxygen-species (ROS)-induced mutations are the most common cause of single nucleotide variant (SNV) drivers in neuroblastoma, including most ALK and Ras pathway SNVs.  ROS-induced mutagenesis is both an early event, as it causes truncal variants, and continuous as it also induces relapse-specific mutations. ROS-induced mutations are more abundant in neuroblastomas with MYCN amplification, 17q gains, and increased expression of mitochondrial ribosome genes. We observe recurrent FGFR1 N546K or internal tandem duplication variants in 6 patients and ALK N-terminal structural alterations in 5 samples, identifying additional patients amenable to precision therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-02T18:58:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003932","title":"Polymorphisms in the mitochondrial genome are associated with bullous pemphigoid in Germans","description":"Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and is characterized by the generation of autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date. Therefore, we sequenced the whole mtDNA of German BP patients (n=180) and age- and sex-matched healthy controls (n=188) using next generation sequencing (NGS) technology, followed by the replication study using Sanger sequencing of an additional independent BP (n=89) and control cohort (n=104). While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency\nin BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (p= 0.1448, Fisher’s exact test). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T&gt;C, m.11914G&gt;A, m.16051A&gt;G, and m.16162A&gt;G, were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p=0.0017, p=0.0132, p=0.0129, and p=0.0076, respectively, Peto’s test). In summary, our study is the first to interrogate the whole mtDNA in BP patients and controls and to implicate multiple novel mtDNA variants in disease susceptibility. Studies using larger cohorts and more diverse populations are warranted to explore the functional consequences of the mtDNA variants identified in this study on immune and skin cells to understand their contributions to BP pathology.","abstract":"Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and is characterized by the generation of autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date. Therefore, we sequenced the whole mtDNA of German BP patients (n=180) and age- and sex-matched healthy controls (n=188) using next generation sequencing (NGS) technology, followed by the replication study using Sanger sequencing of an additional independent BP (n=89) and control cohort (n=104). While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency\nin BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (p= 0.1448, Fisher’s exact test). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T&gt;C, m.11914G&gt;A, m.16051A&gt;G, and m.16162A&gt;G, were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p=0.0017, p=0.0132, p=0.0129, and p=0.0076, respectively, Peto’s test). In summary, our study is the first to interrogate the whole mtDNA in BP patients and controls and to implicate multiple novel mtDNA variants in disease susceptibility. Studies using larger cohorts and more diverse populations are warranted to explore the functional consequences of the mtDNA variants identified in this study on immune and skin cells to understand their contributions to BP pathology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-03T10:33:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003933","title":"ImmunoAgeing_Colonies","description":"Using patterns of shared mutations between haematopoietic stem cells in 14 individuals with clonal haematpoiesis, we aim to determine the timing of somatic mutation acquisition.","abstract":"Using patterns of shared mutations between haematopoietic stem cells in 14 individuals with clonal haematpoiesis, we aim to determine the timing of somatic mutation acquisition.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-03T16:20:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003934","title":"Mutational signature in colorectal cancer induced by genotoxic pks+ E. coli","description":"Various species of the intestinal microbiota have been associated with the\ndevelopment of colorectal cancer (CRC), yet a direct role of bacteria in the\noccurrence of oncogenic mutations has not been established. Escherichia coli can\ncarry the pathogenicity island pks, which encodes a set of enzymes that\nsynthesize colibactin. This compound alkylates DNA on adenine residues and\ninduces double strand breaks in cultured cells. Here, we exposed human intestinal\norganoids to genotoxic pks+ Escherichia coli by repeated luminal injection over a\nperiod of 5 months. Whole genome sequencing (WGS) of clonal organoids before\nand after this exposure reveals a distinct mutational signature, absent from\norganoids injected with isogenic pks-mutant bacteria. The same mutational\nsignature is detected in a subset of 3668 human metastatic cancer genomes,\npredominantly in a subset of CRC cases. Our study describes a distinct mutational\nsignature in CRC and implies that the underlying mutational process directly\nresults from past exposure to bacteria carrying the colibactin-producing pks\npathogenicity island.","abstract":"Various species of the intestinal microbiota have been associated with the\ndevelopment of colorectal cancer (CRC), yet a direct role of bacteria in the\noccurrence of oncogenic mutations has not been established. Escherichia coli can\ncarry the pathogenicity island pks, which encodes a set of enzymes that\nsynthesize colibactin. This compound alkylates DNA on adenine residues and\ninduces double strand breaks in cultured cells. Here, we exposed human intestinal\norganoids to genotoxic pks+ Escherichia coli by repeated luminal injection over a\nperiod of 5 months. Whole genome sequencing (WGS) of clonal organoids before\nand after this exposure reveals a distinct mutational signature, absent from\norganoids injected with isogenic pks-mutant bacteria. The same mutational\nsignature is detected in a subset of 3668 human metastatic cancer genomes,\npredominantly in a subset of CRC cases. Our study describes a distinct mutational\nsignature in CRC and implies that the underlying mutational process directly\nresults from past exposure to bacteria carrying the colibactin-producing pks\npathogenicity island.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-04T09:48:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003935","title":"Kidney_transplant_nephrectomy_scRNAseq","description":"Single cell transcriptomics study of tissue from human kidney transplant nephrectomies\nTissue is acquired from kidney transplant nephrectomies, homogenised and disaggregated to a single cell suspension prior to droplet encapsulation single cell RNAseq (10X protocol) or plate based single cell RNAseq (SS2 protocol). \n\nHuman tissues, including the kidney are seeded with a tissue resident immune cell network throughout life. These cells may self renew in situ or be replaced by circulating precursors which enter the tissue in response to tissue specific niche and inflammatory signals. We are using single cell RNA sequencing of kidney transplant nephrectomy tissue to 1) understand the immune cell populations which are resident within the human kidney 2) identify which of these populations is donor or recipient derived. 3) Uncover the temporal dynamics of donor/recipient chimerism in the the human kidney following transplantation. 4) Understand transcriptional differences between organs removed for a variety of reasons (infection, chronic rejection, vascular emergencies)\n\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Single cell transcriptomics study of tissue from human kidney transplant nephrectomies\nTissue is acquired from kidney transplant nephrectomies, homogenised and disaggregated to a single cell suspension prior to droplet encapsulation single cell RNAseq (10X protocol) or plate based single cell RNAseq (SS2 protocol). \n\nHuman tissues, including the kidney are seeded with a tissue resident immune cell network throughout life. These cells may self renew in situ or be replaced by circulating precursors which enter the tissue in response to tissue specific niche and inflammatory signals. We are using single cell RNA sequencing of kidney transplant nephrectomy tissue to 1) understand the immune cell populations which are resident within the human kidney 2) identify which of these populations is donor or recipient derived. 3) Uncover the temporal dynamics of donor/recipient chimerism in the the human kidney following transplantation. 4) Understand transcriptional differences between organs removed for a variety of reasons (infection, chronic rejection, vascular emergencies)\n\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-04T10:46:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003936","title":"Genotype data from a German GWAS conducted on 834 childhood acute lymphoblastic leukaemia (cALL) on a Illumina OmniExpress-12v1.0 arrays.","description":null,"abstract":"Acute lymphoblastic leukemia (ALL) is the major pediatric cancer diagnosed in economically developed countries with B-cell precursor (BCP)-ALL, accounting for approximately 70% of ALL.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003937","title":"Genotype data from a United Kingdom GWAS conducted on 824 childhood acute lymphoblastic leukaemia (cALL) on Illumina Infinium Human 370Duo BeadChips","description":"To identify genetic risk variants for childhood acute lymphoblastic leukaemia (cALL) a genome-wide association study (GWAS) was conducted on cases recruited through the UKCCS, UK MRC ALL 97(99) trial and NICR. Genotyping for the GWA studies was conducted by Illumina Service laboratory using the Illumina Infinium Human 370Duo BeadChips according to Illumina protocols.","abstract":"To identify genetic risk variants for childhood acute lymphoblastic leukaemia (cALL) a genome-wide association study (GWAS) was conducted on cases recruited through the UKCCS, UK MRC ALL 97(99) trial and NICR. Genotyping for the GWA studies was conducted by Illumina Service laboratory using the Illumina Infinium Human 370Duo BeadChips according to Illumina protocols.","study_type":"Other","pubmed_ids":[19684604],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003938","title":"Analysis_of_Immunoglobulin_gene_repertoires_in_the_memory_B_cell_and_plasmablasts_responses_to_Plasmodium_falciparum_infection_in_children_and_adults_with_different_levels_of_pre_existing_exposure","description":"We will extract RNA from human B cells. Primers that target the Variable, Diversity and Joining (VDJ) regions of both the heavy and light chain segments of the antibodies will be used to amplify the immunoglobulin gene. The amplicons will then undergo another PCR cycle to insert illumina adapters and library preparation for illumina sequencing. The indexed amplicons will then be sequenced on the MiSeq 300PE libraries without shearing and with 20% Phix spiked In.  The reads obtained will then undergo quality control and analyzed. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The reads will then be analyzed and the analysis will include understanding repertoires features such as clonal expansion, class-switcihin and somatic hypermutations within the context of malaria. The other analysis will also be used to understand the allelic characterization between different individuals. Thiw will help inform how the adaptive immunity developes during malaria infection and what constitutes a protective response.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003939","title":"EFFORT - metagenome-wide cross-sectional study of occupational resistome exposure","description":null,"abstract":"By studying the entire human faecal resistome and associated microbiome, the diversity and abundance of faecal antimicrobial resistance genes (ARGs) can be comprehensively characterized. Prior culture-based studies have shown associations between occupational exposure to livestock and carriage of specific antimicrobial resistant bacteria. Using shotgun metagenomics, the present study investigated 194 faecal resistomes and bacteriomes from humans occupationally exposed to ARGs in livestock (pig and poultry farmers, employees and family members, pig slaughterhouse workers) and a control population (‘Lifelines’ cohort) in the Netherlands.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003940","title":"Genetics of nodal marginal zone lymphoma","description":"We performed whole exome sequencing (WES) and transcriptomic analysis to investigate genetic features of nodal marginal zone lymphoma.","abstract":"We performed whole exome sequencing (WES) and transcriptomic analysis to investigate genetic features of nodal marginal zone lymphoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003941","title":"Germline MBD4 Mutations and Predisposition to Uveal Melanoma","description":"Uveal melanoma (UM) arises from malignant transformation of melanocytes from the uveal tract. This rare tumor has a poor outcome with frequent liver metastases and primary resistance to treatment1. The only strong predisposing condition for UM is the BAP1 tumor predisposition syndrome due to germline BAP1 deleterious mutations. UMs are generally characterized by a very low tumor mutation burden (TMB). However, some UMs display a high level of CpG to TpG mutations associated with MBD4 inactivation. Here, we explored the incidence of germline MBD4 variants in a consecutive series of 1, 099 primary UMs, and identified 8 deleterious MBD4 mutations, an aprox 10-fold increased incidence compared with the general population. These mutations were associated with a high TMB in tested UMs. We thus demonstrated that MBD4 is the second major predisposing gene for UM.","abstract":"Uveal melanoma (UM) arises from malignant transformation of melanocytes from the uveal tract. This rare tumor has a poor outcome with frequent liver metastases and primary resistance to treatment1. The only strong predisposing condition for UM is the BAP1 tumor predisposition syndrome due to germline BAP1 deleterious mutations. UMs are generally characterized by a very low tumor mutation burden (TMB). However, some UMs display a high level of CpG to TpG mutations associated with MBD4 inactivation. Here, we explored the incidence of germline MBD4 variants in a consecutive series of 1, 099 primary UMs, and identified 8 deleterious MBD4 mutations, an aprox 10-fold increased incidence compared with the general population. These mutations were associated with a high TMB in tested UMs. We thus demonstrated that MBD4 is the second major predisposing gene for UM.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-07T16:02:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003942","title":"Deep intronic homozygous variation in PSMC3 causes a syndromic neurosensory disorder combining deafness and cataract","description":"The association of congenital deafness and early-onset cataracts inherited as a recessive trait is a rare combination described in only a few syndromes with very few genes identified to date.\nWe propose that the PSMC3 proteasome subunit dysfunction leads to a novel human syndrome that includes early-onset cataracts and deafness and suggest that Rpt5 plays a major role in inner ear and lens development.","abstract":"The association of congenital deafness and early-onset cataracts inherited as a recessive trait is a rare combination described in only a few syndromes with very few genes identified to date.\nWe propose that the PSMC3 proteasome subunit dysfunction leads to a novel human syndrome that includes early-onset cataracts and deafness and suggest that Rpt5 plays a major role in inner ear and lens development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-07T16:30:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003943","title":"EFFORT - metagenome-wide cross-sectional study of occupational resistome exposure","description":null,"abstract":"By studying the entire human faecal resistome and associated microbiome, the diversity and abundance of faecal antimicrobial resistance genes (ARGs) can be comprehensively characterized. Prior culture-based studies have shown associations between occupational exposure to livestock and carriage of specific antimicrobial resistant bacteria. Using shotgun metagenomics, the present study investigated 194 faecal resistomes and bacteriomes from humans occupationally exposed to ARGs in livestock (pig and poultry farmers, employees and family members, pig slaughterhouse workers) and a control population (‘Lifelines’ cohort) in the Netherlands.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003944","title":"Description and determinants of the faecal resistome and microbiome of farmers and slaughterhouse workers: a metagenome-wide cross-sectional study.","description":"Within this study, we extracted DNA of 194 stool samples of persons living or working on pig and broiler farms (54 pig farmers, 24 broiler farmers), 70 pig slaughterhouse workers and 46 control subjects (Lifelines population living in the Northern parts of the Netherlands, and without recent antimicrobial use and occupational livestock contact). Total DNA was sequenced and metagenomic analysis was performed. Subsequently, the faecal resistomes and microbiomes were described and analysed (doi: 10.1016/j.envint.2020.105939). \n\nHighlights study: \n• Food chain workers are exposed to antimicrobial resistant (AMR) bacteria in livestock. • We describe faecal resistomes and microbiomes of farmers and slaughterhouse workers. • Faecal AMR gene loads in pork exposed workers exceed those in broiler farmers/controls. • Resistome and microbiome differences are shown between and within occupational groups. • On-farm working hours and working/living on a pig farm determine the faecal resistome. • Contact with livestock may be a determinant for human AMR gene carriage.\n\nThis study is part of the EFFORT project: http://www.effort-against-amr.eu/.","abstract":"Within this study, we extracted DNA of 194 stool samples of persons living or working on pig and broiler farms (54 pig farmers, 24 broiler farmers), 70 pig slaughterhouse workers and 46 control subjects (Lifelines population living in the Northern parts of the Netherlands, and without recent antimicrobial use and occupational livestock contact). Total DNA was sequenced and metagenomic analysis was performed. Subsequently, the faecal resistomes and microbiomes were described and analysed (doi: 10.1016/j.envint.2020.105939). \n\nHighlights study: \n• Food chain workers are exposed to antimicrobial resistant (AMR) bacteria in livestock. • We describe faecal resistomes and microbiomes of farmers and slaughterhouse workers. • Faecal AMR gene loads in pork exposed workers exceed those in broiler farmers/controls. • Resistome and microbiome differences are shown between and within occupational groups. • On-farm working hours and working/living on a pig farm determine the faecal resistome. • Contact with livestock may be a determinant for human AMR gene carriage.\n\nThis study is part of the EFFORT project: http://www.effort-against-amr.eu/.","study_type":"Other","pubmed_ids":[32679392],"external_links":null,"is_released":true,"released_date":"2019-10-08T08:14:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003945","title":"Exon4-mutations in KRAS Affect MEK-ERK and Pi3K-AKT Signaling in Multiple Myeloma","description":"Approximately 40% of MM cases harbor a point mutation in either KRAS or NRAS. However, it is still unclear whether RAS-mutations are associated with disease outcome. Specifically, no information exists whether KRAS-mutations have an impact on survival in MM patients at diagnosis that were treated with novel agents (e.g. bortezomib, lenalidomide). Targeting KRAS directly for therapeutic purposes is still impossible, but recently the first covalent mutant-specific inhibitor targeting KRASG12C made it into clinical trials. However, other KRAS-hotspot-mutations exist in MM patients, including the less common exon4-mutations. Within the current study, the coding regions of KRAS in 80 MM patients at diagnosis, uniformly treated with bortezomib and high-dose chemotherapy, were deep-sequenced. Moreover, the functional impact of KRASG12A as well as the two exon4-mutations A146T (AMO1) and A146V (MM patient) on different survival pathways was investigated. Specifically, an siRNA-mediated knockdown in AMO1 was performed and KRASWT, KRASG12A, KRAS146T and KRAS146V were overexpressed in the KRASWT cell lines JJN3 and OPM2 using lentiviral transduction and the transposase based Sleeping Beauty system. KRAS-mutations were not associated with survival. Yet, the expression of all KRAS-mutants had an impact on MEK/ERK-signaling in two independent MM cell lines and on AKT/PI3K-signaling in one MM cell line.","abstract":"Approximately 40% of MM cases harbor a point mutation in either KRAS or NRAS. However, it is still unclear whether RAS-mutations are associated with disease outcome. Specifically, no information exists whether KRAS-mutations have an impact on survival in MM patients at diagnosis that were treated with novel agents (e.g. bortezomib, lenalidomide). Targeting KRAS directly for therapeutic purposes is still impossible, but recently the first covalent mutant-specific inhibitor targeting KRASG12C made it into clinical trials. However, other KRAS-hotspot-mutations exist in MM patients, including the less common exon4-mutations. Within the current study, the coding regions of KRAS in 80 MM patients at diagnosis, uniformly treated with bortezomib and high-dose chemotherapy, were deep-sequenced. Moreover, the functional impact of KRASG12A as well as the two exon4-mutations A146T (AMO1) and A146V (MM patient) on different survival pathways was investigated. Specifically, an siRNA-mediated knockdown in AMO1 was performed and KRASWT, KRASG12A, KRAS146T and KRAS146V were overexpressed in the KRASWT cell lines JJN3 and OPM2 using lentiviral transduction and the transposase based Sleeping Beauty system. KRAS-mutations were not associated with survival. Yet, the expression of all KRAS-mutants had an impact on MEK/ERK-signaling in two independent MM cell lines and on AKT/PI3K-signaling in one MM cell line.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003946","title":"Natural Killer Cell Plasticity During IL-15-driven Homeostatic Proliferation","description":"Here we performed single-cell RNA sequencing to address repertoire stability and subset plasticity during IL-15 driven homeostatic proliferation. Sorted NK cell subsets representing discrete stages of NK cell differentiation are compared with the corresponding subsets after proliferation and further sorted into two subsets depending on the rate of proliferation.","abstract":"Here we performed single-cell RNA sequencing to address repertoire stability and subset plasticity during IL-15 driven homeostatic proliferation. Sorted NK cell subsets representing discrete stages of NK cell differentiation are compared with the corresponding subsets after proliferation and further sorted into two subsets depending on the rate of proliferation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-08T14:45:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003947","title":"HG__I3516_FunGen_OA_2019_2020_DNA","description":"OA affects &gt;40% of individuals over 70y and is a leading cause of pain and loss of physical function in the UK, affecting 8.5 million patients. The molecular changes leading to the pathogenesis of OA are still poorly understood. We have already obtained diseased and non-diseased tissue (cartilage) following total knee replacement surgery, coupled with a blood sample. This study follows on from previous successful work with UK-based orthopaedic surgeon collaborators. We aim to have omics (RNAseq, proteomics and methylation) data with and whole genome sequence (WGS) data for all individuals in the collection. Here we wish to expand on the existing RNAseq data to include ~50 samples which will boost the sample size to ~250. In additional we will generate whole genome sequencing for all ~250 individuals that we have omics data from and we will integrate the genome data with the omics data to characterize genes, pathways and networks that underlie osteaoarthritis.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"OA affects &gt;40% of individuals over 70y and is a leading cause of pain and loss of physical function in the UK, affecting 8.5 million patients. The molecular changes leading to the pathogenesis of OA are still poorly understood. We have already obtained diseased and non-diseased tissue (cartilage) following total knee replacement surgery, coupled with a blood sample. This study follows on from previous successful work with UK-based orthopaedic surgeon collaborators. We have omics (RNAseq, proteomics and methylation) data with and here we generate whole genome sequence (WGS) data for all ~250 individuals in the collection.   We will integrate the genome data with the omics data to characterize genes, pathways and networks that underlie osteaoarthritis.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003948","title":"Methylome and engram stability","description":null,"abstract":"Samples are derived from normal mouse neuronic cells or those overexpressing DNMT3a2. Aim is to identify differentially methylated gene promoters and enhancers by WGBS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003949","title":"Molecular profiling of DLBCL patients treated in the HOVON84 trial","description":"Using a comprehensive NGS assay for simultaneous screening of mutations, copy number alterations, and translocations, 5 biology-based risk profiles could be reproduced in a Dutch DLBCL population and validated for outcome prediction. This approach will enable application as a diagnostic tool to select DLBCL patients for risk adapted treatment and help to develop biomarker-driven clinical trials for personalized medicine.","abstract":"Using a comprehensive NGS assay for simultaneous screening of mutations, copy number alterations, and translocations, 5 biology-based risk profiles could be reproduced in a Dutch DLBCL population and validated for outcome prediction. This approach will enable application as a diagnostic tool to select DLBCL patients for risk adapted treatment and help to develop biomarker-driven clinical trials for personalized medicine.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-10T10:10:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003950","title":"Characterization of HCV-specific CD4 T cells during DAA-Therapy","description":"Background: \nChronic HCV-infection is characterized by a severe impairment of HCV-specific CD4 T cell help that is driven by chronic antigen stimulation. We aimed to study the fate of HCV-specific CD4 T cells after viral elimination.\n\nMethods:\nHCV-specific CD4 T cell responses were longitudinally analyzed using MHC class II tetramer-technology, multicolor flow cytometry and RNA sequencing in a cohort of chronically HCV-infected patients undergoing therapy with direct-acting antivirals. In addition, HCV-specific neutralizing antibodies and CXCL13 levels were analyzed. \n\nResults: \nWe observed that the frequency of HCV-specific CD4 T cells increased within two weeks after initiation of DAA therapy. Multicolor flow cytometry revealed a downregulation of exhaustion and activation markers and an upregulation of memory-associated markers. While cells with a Th1 phenotype were the predominant subset at baseline, cells with phenotypic and transcriptional characteristics of follicular T helper cells increasingly shaped the circulating HCV-specific CD4 T cell repertoire, suggesting antigen-independent survival of this subset. These changes were accompanied by a decline of HCV-specific neutralizing antibodies and the germinal center activity. \n\nConclusion: \nWe identified a population of HCV-specific CD4 T cells with a follicular T helper cell signature that is maintained after therapy-induced elimination of persistent infection and may constitute an important target population for vaccination efforts to prevent re-infection and immunotherapeutic approaches for persistent viral infections.","abstract":"Background: \nChronic HCV-infection is characterized by a severe impairment of HCV-specific CD4 T cell help that is driven by chronic antigen stimulation. We aimed to study the fate of HCV-specific CD4 T cells after viral elimination.\n\nMethods:\nHCV-specific CD4 T cell responses were longitudinally analyzed using MHC class II tetramer-technology, multicolor flow cytometry and RNA sequencing in a cohort of chronically HCV-infected patients undergoing therapy with direct-acting antivirals. In addition, HCV-specific neutralizing antibodies and CXCL13 levels were analyzed. \n\nResults: \nWe observed that the frequency of HCV-specific CD4 T cells increased within two weeks after initiation of DAA therapy. Multicolor flow cytometry revealed a downregulation of exhaustion and activation markers and an upregulation of memory-associated markers. While cells with a Th1 phenotype were the predominant subset at baseline, cells with phenotypic and transcriptional characteristics of follicular T helper cells increasingly shaped the circulating HCV-specific CD4 T cell repertoire, suggesting antigen-independent survival of this subset. These changes were accompanied by a decline of HCV-specific neutralizing antibodies and the germinal center activity. \n\nConclusion: \nWe identified a population of HCV-specific CD4 T cells with a follicular T helper cell signature that is maintained after therapy-induced elimination of persistent infection and may constitute an important target population for vaccination efforts to prevent re-infection and immunotherapeutic approaches for persistent viral infections.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-10T10:31:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003951","title":"CRISPR-based adenine editors correct nonsense mutations in a cystic fibrosis organoid biobank.","description":null,"abstract":"Adenine base editing (ABE) enable enzymatic conversion from A-T into G-C base pairs. ABE hold promise for clinical application, as it does not depend on the introduction of double-strand breaks, contrary to conventional CRISPR/Cas9-mediated genome engineering. Here we describe a cystic fibrosis (CF) intestinal organoid biobank, representing 646 patients, of which ~20% can theoretically be repaired by ABE. We apply the SpCas9-ABE (PAM recognition sequence: NGG) and the xCas9-ABE (PAM recognition sequence: NGN) on four selected CF organoid samples. Genetic and functional repair was obtained in all four cases, while whole genome sequencing (WGS) of corrected lines of two patients did not detect off-target mutations. These observations exemplify the value of large, patient-derived organoid biobanks representing hereditary disease, and indicate that ABE may be safely applied in human cells. \nWhole genome sequencing of Cas9 repaired cystic fibrosis organoids\nThree SpCas9-ABE (R785X/R785X) and three xCas9-ABE-repaired organoid clones (F508del/R553X) and their respective unrepaired control organoids were paired-end whole genome sequenced using Illumina Novaseq 6000 system.  This WGS confirmed the Cas9 repair worked in these organoids and showed no off-target hits nor no mutational hotspots created by the repair system.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-10T12:03:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003952","title":"Targeted_sequencing_of_embryonic_variants___Warm_Autopsy","description":"Targeted sequencing of variants previously identified as embryonic from phylogenetic tree building of LCM WGS of PD28690.","abstract":"Targeted sequencing of variants previously identified as embryonic from phylogenetic tree building of LCM WGS of PD28690.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-10T14:13:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003953","title":"Glioblastoma epigenome profiling identifies SOX10 as a master regulator of molecular tumour subtype","description":"Glioblastoma in adult patients are classified into four subtypes, IDH, MES, RTK I, and RTK II, based on DNA methylation and RNA expression data. Tumour subtype transitions commonly occur during the treatment of glioblastoma patients, and transitions to the mesenchymal (MES) subtype have been associated with therapy resistance and adverse prognosis. Here, we generate DNA methylome and histone modification data of glioblastoma primary tumours and show that glioblastoma subtypes differ by their enhancer landscapes. Using Core Regulatory Circuitry analysis of H3K27ac data, and independent analysis of RNA-derived gene regulatory networks, we identified 38 subtype master regulators whose cell type-specific activities we mapped in single-cell RNA sequencing data. These analyses identified the chromatin modifier SRY-Box 10 (SOX10) as a master regulator in tumours of the RTK I subtype. In functional studies we demonstrate that SOX10 loss causes a transition of RTK I tumour cells to a mesenchymal cellular state by altering the accessibility of enhancer-rich chromatin regions and their occupancy by Bromodomain Containing 4 (BRD4), a dynamic constituent of super-enhancers. Treatment with the BRD4 inhibitor JQ1 blocked this transition. These data demonstrate the fundamental role of enhancer chromatin remodelling and master regulator activity in the establishment, maintenance and plasticity of glioblastoma cellular states. We also make our data publically browsable at https://dkfz-b060.github.io/gb_browse/","abstract":"Glioblastoma in adult patients are classified into four subtypes, IDH, MES, RTK I, and RTK II, based on DNA methylation and RNA expression data. Tumour subtype transitions commonly occur during the treatment of glioblastoma patients, and transitions to the mesenchymal (MES) subtype have been associated with therapy resistance and adverse prognosis. Here, we generate DNA methylome and histone modification data of glioblastoma primary tumours and show that glioblastoma subtypes differ by their enhancer landscapes. Using Core Regulatory Circuitry analysis of H3K27ac data, and independent analysis of RNA-derived gene regulatory networks, we identified 38 subtype master regulators whose cell type-specific activities we mapped in single-cell RNA sequencing data. These analyses identified the chromatin modifier SRY-Box 10 (SOX10) as a master regulator in tumours of the RTK I subtype. In functional studies we demonstrate that SOX10 loss causes a transition of RTK I tumour cells to a mesenchymal cellular state by altering the accessibility of enhancer-rich chromatin regions and their occupancy by Bromodomain Containing 4 (BRD4), a dynamic constituent of super-enhancers. Treatment with the BRD4 inhibitor JQ1 blocked this transition. These data demonstrate the fundamental role of enhancer chromatin remodelling and master regulator activity in the establishment, maintenance and plasticity of glioblastoma cellular states. We also make our data publically browsable at https://dkfz-b060.github.io/gb_browse/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-10T15:46:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003954","title":"Characterization of exhausted HCV-specific CD8 T cells","description":null,"abstract":"Please write abstract here","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003955","title":"Genomic landscape of signals of positive natural selection in North Eurasia","description":"We searched for the genomic signatures of positive selection in the genome-wide data of 432 people from eight different northern Russian populations (Russians from the Archangelsky and Vologdsky regions, Izhemski Komi, Priluzski Komi, Veps, Khanty, Mansi and Nenets) who were genotyped using microarrays for 700,000 SNPs (InfiniumOmniExpress-24v1-2_A1) through testing the extended haplotype homozigosity (EHH).","abstract":"We searched for the genomic signatures of positive selection in the genome-wide data of 432 people from eight different northern Russian populations (Russians from the Archangelsky and Vologdsky regions, Izhemski Komi, Priluzski Komi, Veps, Khanty, Mansi and Nenets) who were genotyped using microarrays for 700,000 SNPs (InfiniumOmniExpress-24v1-2_A1) through testing the extended haplotype homozigosity (EHH).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-14T20:56:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003956","title":"MGMT promoter methylation level in newly diagnosed IDH-mutant low-grade glioma is a predictor of temozolomide-driven hypermutation at recurrence.","description":"Emerging data suggest that a subset of patients with diffuse IDH-mutant low-grade glioma (LGG) who receive adjuvant temozolomide (TMZ) recur with hypermutation in association with malignant progression to higher-grade tumors. Identifying a biomarker that predicts risk of developing TMZ-associated hypermutation may inform patient monitoring and treatment decisions, ultimately improving clinical management for LGG. MGMT encodes O6-methylguanine-DNA methyltransferase, a DNA repair protein that removes cytotoxic and potentially mutagenic lesions induced by TMZ. Here, we conduct a hypothesis-driven investigation of MGMT promoter methylation level in initial LGG tumors as a predictor of TMZ-associated hypermutation at recurrence. We characterize MGMT promoter methylation in tissue samples from initial tumors and recurrences using a quantitative, high-throughput deep sequencing assay. We evaluate hypermutation status in tumors by exome sequencing. In our patient cohort, average methylation level at the MGMT promoter is significantly higher in initial tumors of patients that develop hypermutation at recurrence relative to initial tumors of patients that do not. Methylation level in initial tumors can predict hypermutation at recurrence in univariate models and multivariate models that incorporate patient age and molecular subtype. MGMT promoter methylation level in initial tumors of LGG patients is a significant predictor of TMZ-associated hypermutation at recurrence and may serve as a clinical biomarker for informing patient monitoring and treatment decisions.","abstract":"Emerging data suggest that a subset of patients with diffuse IDH-mutant low-grade glioma (LGG) who receive adjuvant temozolomide (TMZ) recur with hypermutation in association with malignant progression to higher-grade tumors. Identifying a biomarker that predicts risk of developing TMZ-associated hypermutation may inform patient monitoring and treatment decisions, ultimately improving clinical management for LGG. MGMT encodes O6-methylguanine-DNA methyltransferase, a DNA repair protein that removes cytotoxic and potentially mutagenic lesions induced by TMZ. Here, we conduct a hypothesis-driven investigation of MGMT promoter methylation level in initial LGG tumors as a predictor of TMZ-associated hypermutation at recurrence. We characterize MGMT promoter methylation in tissue samples from initial tumors and recurrences using a quantitative, high-throughput deep sequencing assay. We evaluate hypermutation status in tumors by exome sequencing. In our patient cohort, average methylation level at the MGMT promoter is significantly higher in initial tumors of patients that develop hypermutation at recurrence relative to initial tumors of patients that do not. Methylation level in initial tumors can predict hypermutation at recurrence in univariate models and multivariate models that incorporate patient age and molecular subtype. MGMT promoter methylation level in initial tumors of LGG patients is a significant predictor of TMZ-associated hypermutation at recurrence and may serve as a clinical biomarker for informing patient monitoring and treatment decisions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003957","title":"A comprehensive PDX gastric cancer collection captures cancer cell–intrinsic transcriptional MSI traits","description":null,"abstract":"Gastric cancer (GC) is the world's third leading cause of cancer mortality. In spite of significant therapeutic improvements, the clinical outcome for patients with advanced GC is poor; thus, the identification and validation of novel targets is extremely important from a clinical point of view. We generated a wide gastric cancer PDX platform, whose exploitation will help identify and validate novel 'druggable' targets and optimize therapeutic strategies. Moreover, transcriptomic analysis of GC PDXs allowed the identification of a cancer cell intrinsic MSI signature, recognizing a subset of MSS patients with MSI transcriptional traits, endowed with better prognosis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003958","title":"genome-wide cfDNA methylation analysis","description":"To characterise cfDNA methylome in metastatic prostate cancer","abstract":"To characterise cfDNA methylome in metastatic prostate cancer","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-15T11:43:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003959","title":"Genomic validation of the revised Bethesda criteria in terms of pathogenesis and oncologic significance","description":null,"abstract":"To know genomic alterations of the respective situation of the revised Bethesda criteria, we investigated the impact of somatic variants and gene expression using colorectal tumor tissues. Using Exome-seq and RNAseq analysis, we identified novel somatic variants that are significantly associated with Bethesda criteria. Using the markers, we predicted the the therapeutic target of familial colorectal cancer. This series includes only the Exome-seq data.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003960","title":"Characterization of HCV-specific CD4 T cells during DAA-Therapy","description":null,"abstract":"Background: \nChronic HCV-infection is characterized by a severe impairment of HCV-specific CD4 T cell help that is driven by chronic antigen stimulation. We aimed to study the fate of HCV-specific CD4 T cells after viral elimination.\n\nMethods:\nHCV-specific CD4 T cell responses were longitudinally analyzed using MHC class II tetramer-technology, multicolor flow cytometry and RNA sequencing in a cohort of chronically HCV-infected patients undergoing therapy with direct-acting antivirals. In addition, HCV-specific neutralizing antibodies and CXCL13 levels were analyzed. \n\nResults: \nWe observed that the frequency of HCV-specific CD4 T cells increased within two weeks after initiation of DAA therapy. Multicolor flow cytometry revealed a downregulation of exhaustion and activation markers and an upregulation of memory-associated markers. While cells with a Th1 phenotype were the predominant subset at baseline, cells with phenotypic and transcriptional characteristics of follicular T helper cells increasingly shaped the circulating HCV-specific CD4 T cell repertoire, suggesting antigen-independent survival of this subset. These changes were accompanied by a decline of HCV-specific neutralizing antibodies and the germinal center activity. \n\nConclusion: \nWe identified a population of HCV-specific CD4 T cells with a follicular T helper cell signature that is maintained after therapy-induced elimination of persistent infection and may constitute an important target population for vaccination efforts to prevent re-infection and immunotherapeutic approaches for persistent viral infections.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003961","title":"Genomic_profiling_of_Adult_ALL__TGS","description":"Targeted pulldown of up to 1500 Adult ALL diagnosis samples","abstract":"Targeted pulldown of up to 1500 Adult ALL diagnosis samples","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003962","title":"Breast implant-associated anaplastic large cell lymphoma shallow whole genome sequencing for copy number analysis and Whole exome sequencing data.","description":"Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) shallow whole genome sequencing of 29 BIA-ALCL patients for copy number analysis and 24 Alk-negative ALCL samples as control cohort. 7 Whole exome sequencing BIA-ALCL samples.","abstract":"Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) shallow whole genome sequencing of 29 BIA-ALCL patients for copy number analysis and 24 Alk-negative ALCL samples as control cohort. 7 Whole exome sequencing BIA-ALCL samples.","study_type":"Other","pubmed_ids":[32898861,33331925],"external_links":null,"is_released":true,"released_date":"2019-10-17T09:49:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003963","title":"Rapid identification of somatic genome rearrangements as personalized biomarkers for blood-based cancer monitoring","description":"Increasing evidence shows the value of circulating tumour DNA (ctDNA) to detect cancer and monitor its progression. Somatic genomic structural variations (SVs) are promising personalized biomarkers for sensitive and specific detection of ctDNA in liquid biopsies. However, accurate, affordable, and fast identification of such SV biomarkers is challenging, which hinders routine use in the clinic. Here, we demonstrate a novel approach - termed SHARC - for rapid discovery of somatic SV breakpoints as personalized tumour biomarkers. SHARC combines low-coverage cancer genome sketching by using Oxford Nanopore portable sequencing with a random forest classification and a dedicated filtering pipeline to enrich for somatic SVs. Our method leverages the real-time and long-read capabilities of Nanopore sequencing to identify somatic SV breakpoints at nucleotide resolution from a tumour biopsy within two days. We applied SHARC to tumour samples of high-grade ovarian and prostate cancer and validated on average 10 somatic SVs per sample with the use of PCR mini-amplicons. Finally, we demonstrate that these somatic SV biomarkers can  be used to detect tumour presence from liquid biopsies in a quantitative manner and we retrospectively monitored treatment response in patients with prostate cancer, demonstrating its potential benefit for clinical practice.","abstract":"Increasing evidence shows the value of circulating tumour DNA (ctDNA) to detect cancer and monitor its progression. Somatic genomic structural variations (SVs) are promising personalized biomarkers for sensitive and specific detection of ctDNA in liquid biopsies. However, accurate, affordable, and fast identification of such SV biomarkers is challenging, which hinders routine use in the clinic. Here, we demonstrate a novel approach - termed SHARC - for rapid discovery of somatic SV breakpoints as personalized tumour biomarkers. SHARC combines low-coverage cancer genome sketching by using Oxford Nanopore portable sequencing with a random forest classification and a dedicated filtering pipeline to enrich for somatic SVs. Our method leverages the real-time and long-read capabilities of Nanopore sequencing to identify somatic SV breakpoints at nucleotide resolution from a tumour biopsy within two days. We applied SHARC to tumour samples of high-grade ovarian and prostate cancer and validated on average 10 somatic SVs per sample with the use of PCR mini-amplicons. Finally, we demonstrate that these somatic SV biomarkers can  be used to detect tumour presence from liquid biopsies in a quantitative manner and we retrospectively monitored treatment response in patients with prostate cancer, demonstrating its potential benefit for clinical practice.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-17T10:50:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003964","title":"Partner-independent fusion gene detection by multiplexed CRISPR/Cas9 enrichment and long-read Nanopore sequencing","description":"Fusion genes are hallmarks of various cancer types and important determinants for diagnosis, prognosis and treatment possibilities. The promiscuity of fusion genes with respect to partner choice and exact breakpoint-positions restricts their detection in the diagnostic setting, even for known and recurrent fusion gene configurations. To accurately identify these gene fusions in an unbiased manner, we developed FUDGE: a FUsion gene Detection assay from Gene Enrichment. FUDGE couples target-selected and strand-specific CRISPR/Cas9 activity for enrichment and detection of fusion gene drivers (e.g. BRAF, EWSR1, KMT2A/MLL) - without prior knowledge of fusion partner or breakpoint-location -  to long-read Nanopore sequencing. FUDGE encompasses a dedicated bioinformatics approach (NanoFG) to detect fusion genes from Nanopore sequencing data. Our strategy is flexible with respect to target choice and enables multiplexed enrichment for simultaneous analysis of several genes in multiple samples in a single sequencing run. We observe on average a 508-fold on-target enrichment and identify fusion breakpoints at nucleotide resolution - all within two days. We demonstrate that FUDGE effectively identifies fusion genes in cancer cell lines, tumor samples and on whole genome amplified DNA irrespective of partner gene or breakpoint-position in 100% of cases. Furthermore, we show that FUDGE is superior to routine diagnostic methods for fusion gene detection. In summary, we have developed a rapid and versatile fusion gene detection assay, providing an unparalleled opportunity for pan-cancer detection of fusion genes in routine diagnostics.","abstract":"Fusion genes are hallmarks of various cancer types and important determinants for diagnosis, prognosis and treatment possibilities. The promiscuity of fusion genes with respect to partner choice and exact breakpoint-positions restricts their detection in the diagnostic setting, even for known and recurrent fusion gene configurations. To accurately identify these gene fusions in an unbiased manner, we developed FUDGE: a FUsion gene Detection assay from Gene Enrichment. FUDGE couples target-selected and strand-specific CRISPR/Cas9 activity for enrichment and detection of fusion gene drivers (e.g. BRAF, EWSR1, KMT2A/MLL) - without prior knowledge of fusion partner or breakpoint-location -  to long-read Nanopore sequencing. FUDGE encompasses a dedicated bioinformatics approach (NanoFG) to detect fusion genes from Nanopore sequencing data. Our strategy is flexible with respect to target choice and enables multiplexed enrichment for simultaneous analysis of several genes in multiple samples in a single sequencing run. We observe on average a 508-fold on-target enrichment and identify fusion breakpoints at nucleotide resolution - all within two days. We demonstrate that FUDGE effectively identifies fusion genes in cancer cell lines, tumor samples and on whole genome amplified DNA irrespective of partner gene or breakpoint-position in 100% of cases. Furthermore, we show that FUDGE is superior to routine diagnostic methods for fusion gene detection. In summary, we have developed a rapid and versatile fusion gene detection assay, providing an unparalleled opportunity for pan-cancer detection of fusion genes in routine diagnostics.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-17T10:59:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003965","title":"Genomic and immune profiling of pre-invasive lung adenocarcinoma v6","description":null,"abstract":"Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003966","title":"Genomic and immune profiling of pre-invasive lung adenocarcinoma v6","description":null,"abstract":"Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003967","title":"STRATAA_RNAseq","description":"Transcriptome signatures of acute typhoid infection\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Transcriptome signatures of acute typhoid infection\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-18T08:40:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003968","title":"Intellectual Disability cases with parents (trios) or affected sibs (sibpairs)","description":"Samples from ID cases negative for CNV through array-CGH were submitted to exome sequencing. \nFamilies with one affected individual underwent trio exome sequencing for identification of de novo variants.\nFamilies with more than one affected child underwent sibpair sequencing for identificatio of shared recessive or x-linked variants.","abstract":"Samples from ID cases negative for CNV through array-CGH were submitted to exome sequencing. \nFamilies with one affected individual underwent trio exome sequencing for identification of de novo variants.\nFamilies with more than one affected child underwent sibpair sequencing for identificatio of shared recessive or x-linked variants.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-18T10:43:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003969","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___GI___POL___WES","description":"Somatic mutations (burdens and signatures) and clonal dynamics in normal human tissues from the gastrointestinal tract of individuals with tumour predisposition syndromes and DNA damage repair defects.","abstract":"The aim of this project is to investigate somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the study of normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to identified and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003970","title":"Whole-exome sequencing of intravascular large B-Cell lymphoma","description":"Intravascular large B-cell lymphoma (IVLBCL) is a unique form of diffuse large B-cell lymphoma (DLBCL) characterized by extranodal cell growth especially in small vessels without systemic lymphadenopathy. The limitation in obtaining sufficient tumor materials hampers understanding the molecular pathogenesis of IVLBCL. We performed whole-exome sequencing of IVLBCL using plasma-derived cell-free DNA (cfDNA) and patient-derived xenograft (PDX) samples.","abstract":"Intravascular large B-cell lymphoma (IVLBCL) is a unique form of diffuse large B-cell lymphoma (DLBCL) characterized by extranodal cell growth especially in small vessels without systemic lymphadenopathy. The limitation in obtaining sufficient tumor materials hampers understanding the molecular pathogenesis of IVLBCL. We performed whole-exome sequencing of IVLBCL using plasma-derived cell-free DNA (cfDNA) and patient-derived xenograft (PDX) samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-18T13:07:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003971","title":"Defective mitophagy and enhanced oxidative stress dictate regulatory T cell impairment in autoimmunity","description":null,"abstract":"Regulatory T cell (Treg) impairment is a common denominator of autoimmune pathologies. Despite the extensive characterization of Treg cell phenotype in autoimmunity, the molecular mechanisms underlying their deterioration remain ill defined. To investigate Treg dysfunction during autoimmunity we performed transcriptomic analysis of CD4+CD25highCD127- Treg cells from peripheral blood of patients with autoimmunity.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003972","title":"Genomic and immune profiling of pre-invasive lung adenocarcinoma","description":"Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.","abstract":"Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003973","title":"Direct Comparative Analysis of 10X Genomics Chromium and Smart-seq2","description":"Single cell RNA sequencing (scRNA-seq) is widely used for profiling transcriptomes of individual cells. The droplet-based 10X Genomics Chromium (10X) approach and the plate-based Smart-seq2 full-length method are two frequently-used scRNA-seq platforms, yet there are only a few thorough and systematic comparisons of their advantages and limitations. Here, by directly comparing the scRNA-seq data by the two platforms from the same samples of CD45- cells, we systematically evaluated their features using a wide spectrum of analysis. Smart-seq2 detected more genes in a cell, especially low abundance transcripts as well as alternatively spliced transcripts, but captured higher proportion of mitochondrial genes. The composite of Smart-seq2 data also resembled bulk RNA-seq data better. For 10X-based data, we observed higher noise for mRNA in the low expression level. Despite the poly(A) enrichment, approximately 10-30% of all detected transcripts by both platforms were from non-coding genes, with lncRNA accounting for a higher proportion in 10X. 10X-based data displayed more severe dropout problem, especially for genes with lower expression levels. However, 10X-data can better detect rare cell types given its ability to cover a large number of cells. In addition, each platform detected different sets of differentially expressed genes between cell clusters, indicating the complementary nature of these technologies. Our comprehensive benchmark analysis offers the basis for selecting the optimal scRNA-seq strategy based on the objectives of each study.","abstract":"Single cell RNA sequencing (scRNA-seq) is widely used for profiling transcriptomes of individual cells. The droplet-based 10X Genomics Chromium (10X) approach and the plate-based Smart-seq2 full-length method are two frequently-used scRNA-seq platforms, yet there are only a few thorough and systematic comparisons of their advantages and limitations. Here, by directly comparing the scRNA-seq data by the two platforms from the same samples of CD45- cells, we systematically evaluated their features using a wide spectrum of analysis. Smart-seq2 detected more genes in a cell, especially low abundance transcripts as well as alternatively spliced transcripts, but captured higher proportion of mitochondrial genes. The composite of Smart-seq2 data also resembled bulk RNA-seq data better. For 10X-based data, we observed higher noise for mRNA in the low expression level. Despite the poly(A) enrichment, approximately 10-30% of all detected transcripts by both platforms were from non-coding genes, with lncRNA accounting for a higher proportion in 10X. 10X-based data displayed more severe dropout problem, especially for genes with lower expression levels. However, 10X-data can better detect rare cell types given its ability to cover a large number of cells. In addition, each platform detected different sets of differentially expressed genes between cell clusters, indicating the complementary nature of these technologies. Our comprehensive benchmark analysis offers the basis for selecting the optimal scRNA-seq strategy based on the objectives of each study.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-20T10:31:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003974","title":"A Unifying Paradigm for Transcriptional Heterogeneity and Squamous Features in Pancreatic Ductal Adenocarcinoma","description":"Pancreatic cancer expression profiles largely reflect a classical or basal-like phenotype. The extent to which these profiles vary within a patient is unknown. We integrated evolutionary analysis and expression profiling in multiregion sampled metastatic pancreatic cancers, finding that squamous features are the histologic correlate of an RNA-seq defined basal-like subtype. In patients with coexisting basal/squamous and classical/glandular morphology, phylogenetic studies revealed that squamous morphology represented a subclonal population in an otherwise classical/glandular tumor. Cancers with squamous features were significantly more likely to have clonal mutations in chromatin modifiers, intercellular heterogeneity for MYC amplification, and entosis. These data provide a unifying paradigm for integrating basal-type expression profiles, squamous histology, and somatic mutations in chromatin modifier genes in the context of clonal evolution of pancreatic cancer.  ","abstract":"Pancreatic cancer expression profiles largely reflect a classical or basal-like phenotype. The extent to which these profiles vary within a patient is unknown. We integrated evolutionary analysis and expression profiling in multiregion sampled metastatic pancreatic cancers, finding that squamous features are the histologic correlate of an RNA-seq defined basal-like subtype. In patients with coexisting basal/squamous and classical/glandular morphology, phylogenetic studies revealed that squamous morphology represented a subclonal population in an otherwise classical/glandular tumor. Cancers with squamous features were significantly more likely to have clonal mutations in chromatin modifiers, intercellular heterogeneity for MYC amplification, and entosis. These data provide a unifying paradigm for integrating basal-type expression profiles, squamous histology, and somatic mutations in chromatin modifier genes in the context of clonal evolution of pancreatic cancer.  ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-21T14:35:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003975","title":"Mutational landscape and patterns of clonal evolution in relapsed pediatric acute lymphoblastic leukemia","description":"Relapse of acute lymphoblastic leukemia (ALL) remains a leading cause of childhood death. Prior studies have shown clonal mutations at relapse often arise from relapse-fated subclones that exist at diagnosis. However, the genomic landscape, evolutionary trajectories and mutational mechanisms driving relapse are incompletely understood. In an analysis of 92 cases of relapsed childhood ALL, incorporating multimodal DNA and RNA sequencing, deep digital mutational tracking and xenografting to formally define clonal structure, we identify 50 significant targets of mutation with distinct patterns of mutational acquisition or enrichment. CREBBP, NOTCH1, and Ras signaling mutations rose from diagnosis subclones, whereas variants in NCOR2, USH2A and NT5C2 were exclusively observed at relapse. Evolutionary modeling and xenografting demonstrated that relapse-fated clones were minor (50%), major (27%) or multiclonal (18%) at diagnosis. Putative second leukemias, including those with lineage shift, were shown to most commonly represent relapse from an ancestral clone rather than a truly independent second primary leukemia. A subset of leukemias prone to repeated relapse exhibited hypermutation driven by at least three distinct mutational processes, resulting in heightened neoepitope burden and potential vulnerability to immunotherapy. Finally, relapse-driving sequence mutations were detected prior to relapse using deep digital PCR at levels comparable to orthogonal approaches to monitor levels of measurable residual disease. These results provide a genomic framework to anticipate and circumvent relapse by earlier detection and targeting of relapse-fated clones.","abstract":"Relapse of acute lymphoblastic leukemia (ALL) remains a leading cause of childhood death. Prior studies have shown clonal mutations at relapse often arise from relapse-fated subclones that exist at diagnosis. However, the genomic landscape, evolutionary trajectories and mutational mechanisms driving relapse are incompletely understood. In an analysis of 92 cases of relapsed childhood ALL, incorporating multimodal DNA and RNA sequencing, deep digital mutational tracking and xenografting to formally define clonal structure, we identify 50 significant targets of mutation with distinct patterns of mutational acquisition or enrichment. CREBBP, NOTCH1, and Ras signaling mutations rose from diagnosis subclones, whereas variants in NCOR2, USH2A and NT5C2 were exclusively observed at relapse. Evolutionary modeling and xenografting demonstrated that relapse-fated clones were minor (50%), major (27%) or multiclonal (18%) at diagnosis. Putative second leukemias, including those with lineage shift, were shown to most commonly represent relapse from an ancestral clone rather than a truly independent second primary leukemia. A subset of leukemias prone to repeated relapse exhibited hypermutation driven by at least three distinct mutational processes, resulting in heightened neoepitope burden and potential vulnerability to immunotherapy. Finally, relapse-driving sequence mutations were detected prior to relapse using deep digital PCR at levels comparable to orthogonal approaches to monitor levels of measurable residual disease. These results provide a genomic framework to anticipate and circumvent relapse by earlier detection and targeting of relapse-fated clones.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-22T18:23:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003976","title":"Phenotypic_characterisation_of_LRRN4CL_over_expression","description":"This study aims to use RNAseq to identify differentially expressed transcripts in human melanoma cells that over-express the cell surface protein, LRRN4CL, relative to empty-vector control cells, to provide mechanistic insight into how LRRN4CL over-expression confers enhanced pulmonary metastatic colonisation abilities.","abstract":"We performed an in vivo CRISPRa screen and identified Lrrn4cl as a cell surface protein whose over-expression confers increased pulmonary metastatic colonisation abilities on tumour cells (of a range of  different tumour types). We have confirmed that over-expression of LRRN4CL in human tumour cells confers the same phenotype. We have determined that this phenotype does not involve the adaptive immune system and is not due to an increased ability of the tumour cells to extravasate from the bloodstream into the lung. In attempt to determine the mechanism of action, we performed in vitro analyses, such as cell growth/proliferation, migration assays, invasion assays and Western blots for markers of EMT, stem cells and metalloproteases, however there were no obvious differences between Lrrn4cl over-expressing cells and control (empty vector) cells. Since the phenotype of Lrrn4cl/LRRN4CL over-expression is only observed in an in vivo context, we dosed mice with human melanoma A375 cells that carry either the LRRN4CL cDNA or empty vector and 21 days later isolated the tumor cells from their lungs. We have extracted RNA from these cells, as well from the cell lines that were used to dose the mice, with a view to perform RNAseq to identify differentially expressed transcripts between the LRRN4CL over-expressing cells versus the control cells (from both in vivo and in vitro contexts), to give us insight into the mechanism of action of LRRN4CL-mediated enhanced pulmonary metastatic colonisation.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-23T17:16:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003977","title":"De_nove_whole_genome_sequencing_of_a_Ewing_sarcoma_cell_line_having_chromosomes_harboring_neocentromere","description":"Determine the genomic features (including chromosome structures, translocation, karyotypes and chromothripsis) of a Ewing Sarcoma cell line, ES-2 carrying a chromosomes harboring neocentromere by performing de nove whole genome sequencing. We will then determine the position of neocentromeres on the chromosomes.","abstract":"We have recently identified neocentromeres in a Ewing Sarcoma cell line, ES-2. According to the immunofluorescence microscopy combined with FISH analysis, the DNA sequqnce where a neocentromere is assembled isderived originally from chromosome 4, but the chromosome harboring neocentromere is likely to be highly rearranged. To understand the precise mechanism of centromere identity, it is important to determine the genomic features of the neocentromere at the sequence level. We would like to determine the chromosome features (the exact sequence of the rearranged chromosomes) surrounding the neocentromere loci as well as the entire chromosome rearrangements in the Ewing sarcoma cell line.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003978","title":"WGS_Bcells_RA","description":"Whole genome sequencing of enriched autoreactive B cells from rheumatoid arthritis patients","abstract":"The aim of this study is to investigate whether B cells in rheumatoid arthritis that are reactive to citrullinated peptides carry disease-relevant somatic mutations.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003979","title":"Activation of IL7RA signalling in human B-lymphoid precursors induces pre-leukemia","description":null,"abstract":"Childhood acute lymphoblastic leukemia (ALL) is preceded by a clinically silent pre-leukemia. Experimental models that authentically re-capitulate disease initiation and progression in human cells are lacking. Herein, we explore these issues in the most common subtype of the poor-prognosis Philadelphia-like (Ph-like) B-cell precursor (BCP) ALL, characterized by aberrant expression of cytokine receptor-like factor-2 (CRLF2) which dimerizes with Interleukin-7 receptor alpha (IL7RA). Whether CRLF2/IL7RA signalling has a role in initiation of human BCP-ALL is unknown.\n\nTo investigate this, we expressed CRLF2 and/or mutationally activated IL7RA in cord-blood CD34+ hematopoietic progenitors and transplanted them into NOD/LtSz-scid IL2Rγnull mice. Detailed immunphenotypic and molecular analyses revealed that activation of the CRLF2/IL7RA pathway induces B-cell differentiation arrest coupled with enhanced self-renewal in-vivo, consistent with a pre-leukemic state.\n\nProgression from pre-leukemia to leukemia in children is rare and associated with an intervening period of several years. Nevertheless, we observed the development of BCP-ALL after a secondary transplant of pre-leukemic cells transduced with mutationally-activated IL7RA. Genomic analysis of the leukemia revealed the loss of CDKN2A/B and IKZF1, typically observed in Ph-like ALL. Single cell gene expression analysis of pre-leukemic and leukemic cells further suggests that the leukemia arose from a subpopulation of CD19+CD10highCD34+ pre-leukemic cells.\n\nThe development of authentic BCP-ALL from CRLF2/IL7RA transduced cells supports the hypothesis that aberrant activation of the CRLF2/IL7RA pathway in human B-cell lineage progenitors creates pre-leukemic state which is vulnerable to transformation. This is the first model of a de-novo Ph-like BCP-ALL development from normal human hematopoietic progenitors in vivo.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-24T16:19:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003980","title":"Molecular Profiles of BRCA1-Associated Ovarian Cancer Treated by Platinum-Based Therapy","description":null,"abstract":"BRCA1-driven ovarian cancers (OC) are characterized by intratumoral heterogeneity: while the majority of malignant cells demonstrate somatic loss of the remaining BRCA1 allele, there are persistent cells with preserved BRCA1 function. These BRCA1-proficient tumor cells rapidly repopulate tumor mass during neoadjuvant chemotherapy. OC relapses arising after treatment holidays are characterized by re-appearance of somatic BRCA1 inactivation. This plasticity of BRCA1 status explains failures of systemic therapy to eradicate tumor clones and accounts for platinum sensitivity of recurrent BRCA1-driven OC.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-25T15:02:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003981","title":"Sequencing data of multiple sarcoma samples for personalized medicine and endotype identification","description":"Sequencing data derived from multiple patient samples was used to guide multiple patient-specific experiments and identify potential therapeutic options. These diseases are rare and high-risk (undifferentiated pleomorphic sarcoma, rhabdomyosarcoma) and thus have few available validated clinical options. This leaves the population of patients with few options if, and when, standard therapy fails to cure or control disease. \n\nAn aspect of the personalize therapy design included the identification of broader disease endotypes (a combination of genetic and clinical data describing patient status) to identify subgroups of the individual disease that could better define treatments and could segment patient populations for deeper preclinical research.","abstract":"Sequencing data derived from multiple patient samples was used to guide multiple patient-specific experiments and identify potential therapeutic options. These diseases are rare and high-risk (undifferentiated pleomorphic sarcoma, rhabdomyosarcoma) and thus have few available validated clinical options. This leaves the population of patients with few options if, and when, standard therapy fails to cure or control disease. \n\nAn aspect of the personalize therapy design included the identification of broader disease endotypes (a combination of genetic and clinical data describing patient status) to identify subgroups of the individual disease that could better define treatments and could segment patient populations for deeper preclinical research.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-25T19:57:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001003982","title":"Increased mutation accumulation during fetal development in Down syndrome","description":"Children with Down syndrome (DS) show a high incidence of leukemia, which is preceded by transient myeloproliferative disorder (TMD) in neonates. TMD is characterized by mutations in GATA1 that accumulate during fetal development, indicating that additional mutagenesis is required for leukemogenesis. Abnormalities in chromosome numbers can result in a mutator phenotype. However, it is unknown whether a trisomy of chromosome 21 (T21) results in enhanced mutation accumulation during human development. Here, we determined the mutational consequences of a constitutive T21 in DS fetuses compared to disomy 21 cells (D21) of D21 fetuses. We found that D21 fetal HPSCs had a higher somatic mutation rate compared to healthy adults HSPCs. Moreover, we observed an increase in somatic mutation load in T21 cells of DS fetuses, which was already apparent during the first cell divisions of embryogenesis. The mutation load could be explained by processes that are active during normal fetal development and were similar to those observed in TMD blast cells. Our study shows that T21 causes an increase in somatic load in fetal cells of DS fetuses, which may contribute to leukemia development early in life.","abstract":"Children with Down syndrome (DS) show a high incidence of leukemia, which is preceded by transient myeloproliferative disorder (TMD) in neonates. TMD is characterized by mutations in GATA1 that accumulate during fetal development, indicating that additional mutagenesis is required for leukemogenesis. Abnormalities in chromosome numbers can result in a mutator phenotype. However, it is unknown whether a trisomy of chromosome 21 (T21) results in enhanced mutation accumulation during human development. Here, we determined the mutational consequences of a constitutive T21 in DS fetuses compared to disomy 21 cells (D21) of D21 fetuses. We found that D21 fetal HPSCs had a higher somatic mutation rate compared to healthy adults HSPCs. Moreover, we observed an increase in somatic mutation load in T21 cells of DS fetuses, which was already apparent during the first cell divisions of embryogenesis. The mutation load could be explained by processes that are active during normal fetal development and were similar to those observed in TMD blast cells. Our study shows that T21 causes an increase in somatic load in fetal cells of DS fetuses, which may contribute to leukemia development early in life.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-28T10:01:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003983","title":"Vietnam_Rotavirus_Vaccine_Perturbation_Study","description":"Investigating the impact of host genetic factors on longitudinal immune response to rotavirus vaccine (Rotarix), in an infant cohort in HCMC, Vietnam.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Rotavirus is the leading cause of diarrhoeal disease in infants and young children globally. Vaccines against rotavirus that are efficacious in developed countries are less efficacious in developing countries, where the disease burden is also the highest. The causes behind this disparity in efficacy are not fully understood, but are likely to comprise a mix of genetic (both host and pathogen) and environmental (e.g. diet, climate, concomitant infection) factors.\nThis study assesses the contribution of host genetics to live-attenuated rotavirus vaccine (Rotarix) response, in a cohort of approx. 1000 infants in HCMC, Vietnam. Patients are genotyped, and longitudinal measurements of the blood transcriptome are taken before and after vaccine doses. This genetic and transcriptomic data is integrated with serological, clinical, and vaccine failure phenotypes. The primary aim is to discover genetic variants (quantitative trait loci) that influence transcriptomic response and/or other vaccine phenotypes, whilst forming hypotheses regarding the regulatory mechanisms by which these variants have their effects.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003984","title":"SCLC ctDNA sequencing","description":"In this study we have sequenced the ctDNA of 28 Small Cell Lung Cancer patients in the TP53 gene, each sample has been sequenced twice.","abstract":"In this study we have sequenced the ctDNA of 28 Small Cell Lung Cancer patients in the TP53 gene, each sample has been sequenced twice.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-28T10:29:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003985","title":"SCLC tumor sequencing","description":"In this study we have sequenced the tumor of 28 Small Cell Lung Cancer patients.","abstract":"In this study we have sequenced the tumor of 28 Small Cell Lung Cancer patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-28T10:29:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003986","title":"Investigation of relapse prediction in infants with MLL-rearranged Acute Lymphoblastic Leukemia","description":"In infants with ALL, accurate relapse prediction would enable treatment strategies that take relapse risk into account, with potential benefits for both low- and high-risk patients. Through analysis of bone marrow biopsies taken at initial diagnosis, we show that single-cell RNA sequencing can predict future relapse occurrence.","abstract":"In infants with ALL, accurate relapse prediction would enable treatment strategies that take relapse risk into account, with potential benefits for both low- and high-risk patients. Through analysis of bone marrow biopsies taken at initial diagnosis, we show that single-cell RNA sequencing can predict future relapse occurrence.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-28T14:02:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003987","title":"SCC ctDNA sequencing","description":"In this study we have sequenced the ctDNA of 28 Squamous Cell Carcinoma patients in the TP53 gene, each sample has been sequenced twice.","abstract":"In this study we have sequenced the ctDNA of 28 Squamous Cell Carcinoma patients in the TP53 gene, each sample has been sequenced twice.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-28T14:52:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003988","title":"SCC tumor sequencing","description":"In this study we have sequenced the tumor of 28 Squamous Cell Carcinoma patients.","abstract":"In this study we have sequenced the tumor of 28 Squamous Cell Carcinoma patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-28T14:52:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003989","title":"circulating-tumor DNA sequencing of healthy samples","description":"In this study we have sequenced the TP53 gene (exons) from circulating-tumor DNA of 125 controls samples. Each ctDNA samples was sequenced independently twice.","abstract":"In this study we have sequenced the TP53 gene (exons) from circulating-tumor DNA of 125 controls samples. Each ctDNA samples was sequenced independently twice.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-28T14:54:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003990","title":"We previously analyzed 9 pheochromocytoma/paraganglioma (PPGL), and reported novel recurrent nonsynonymous mutations in metastatic cases. Here, we explored the functional impact of MYO5B mutations, and analyzed 21 additional primary PPGL tumor cases by exome-sequencing, expression analysis and immunohistochemistry.","description":"Identification of additional cancer-associated genes and secondary mutations driving the metastatic progression in pheochromocytoma and paraganglioma (PPGL) is important. We recently reported novel recurrent nonsynonymous mutations in the MYO5B gene in metastatic PPGL. Here, we explored the functional impact of these MYO5B mutations, and analyzed MYO5B expression in primary PPGL tumor cases in relation to mutation status.Immunohistochemistry and mRNA expression analysis in 30 primary PPGL tumors revealed an increased MYO5B expression in metastatic compared to non-metastatic tumor cases. In addition, subcellular localization of MYO5B protein was altered from cytoplasmatic to membranous in some metastatic tumors, and the strongest and most abnormal expression pattern was observed in a PGL case harboring a MYO5B:p.G1611S mutation. Mutation analysis of additional PPGL tumors revealed additional, and hence recurrent, mutations in the paralog MYO5A. Three missense mutations in MYO5B were functionally studied using site directed mutagenesis and stable transfection into human neuroblastoma cells (SK-N-AS) and embryonic kidney cells (HEK293 cell line). Functional analysis of the mutants verified a significant increased proliferation rate in all MYO5B mutated clones (p.L587P,  p.G1611S, and p.R1641C).  The two somatically derived mutations p.L587P and p.G1611S were also found to increase the migration rate, and all three mutants affected intracellular transport by increased transferrin uptake. Downstream expression analysis of MYO5B mutants demonstrated a transcriptional activation of genes involved in glucose metabolism, proliferation, homeostasis, and migration. Our study validates the functional role of novel MYO5B mutations in proliferation and migration, and suggest the MYO5-pathway to be involved the malignant progression of PPGL tumors.","abstract":"Identification of additional cancer-associated genes and secondary mutations driving the metastatic progression in pheochromocytoma and paraganglioma (PPGL) is important. We recently reported novel recurrent nonsynonymous mutations in the MYO5B gene in metastatic PPGL. Here, we explored the functional impact of these MYO5B mutations, and analyzed MYO5B expression in primary PPGL tumor cases in relation to mutation status.Immunohistochemistry and mRNA expression analysis in 30 primary PPGL tumors revealed an increased MYO5B expression in metastatic compared to non-metastatic tumor cases. In addition, subcellular localization of MYO5B protein was altered from cytoplasmatic to membranous in some metastatic tumors, and the strongest and most abnormal expression pattern was observed in a PGL case harboring a MYO5B:p.G1611S mutation. Mutation analysis of additional PPGL tumors revealed additional, and hence recurrent, mutations in the paralog MYO5A. Three missense mutations in MYO5B were functionally studied using site directed mutagenesis and stable transfection into human neuroblastoma cells (SK-N-AS) and embryonic kidney cells (HEK293 cell line). Functional analysis of the mutants verified a significant increased proliferation rate in all MYO5B mutated clones (p.L587P,  p.G1611S, and p.R1641C).  The two somatically derived mutations p.L587P and p.G1611S were also found to increase the migration rate, and all three mutants affected intracellular transport by increased transferrin uptake. Downstream expression analysis of MYO5B mutants demonstrated a transcriptional activation of genes involved in glucose metabolism, proliferation, homeostasis, and migration. Our study validates the functional role of novel MYO5B mutations in proliferation and migration, and suggest the MYO5-pathway to be involved the malignant progression of PPGL tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003991","title":"MYO5B mutations in Pheochromocytoma/Paraganglioma promote cancer progression","description":"Identification of additional cancer-associated genes and secondary mutations driving the metastatic progression in pheochromocytoma and paraganglioma (PPGL) is important. We recently reported novel recurrent nonsynonymous mutations in the MYO5B gene in metastatic PPGL. Here, we explored the functional impact of these MYO5B mutations, and analyzed MYO5B expression in primary PPGL tumor cases in relation to mutation status.Immunohistochemistry and mRNA expression analysis in 30 primary PPGL tumors revealed an increased MYO5B expression in metastatic compared to non-metastatic tumor cases. In addition, subcellular localization of MYO5B protein was altered from cytoplasmatic to membranous in some metastatic tumors, and the strongest and most abnormal expression pattern was observed in a PGL case harboring a MYO5B:p.G1611S mutation. Mutation analysis of additional PPGL tumors revealed additional, and hence recurrent, mutations in the paralog MYO5A. Three missense mutations in MYO5B were functionally studied using site directed mutagenesis and stable transfection into human neuroblastoma cells (SK-N-AS) and embryonic kidney cells (HEK293 cell line). Functional analysis of the mutants verified a significant increased proliferation rate in all MYO5B mutated clones (p.L587P,  p.G1611S, and p.R1641C).  The two somatically derived mutations p.L587P and p.G1611S were also found to increase the migration rate, and all three mutants affected intracellular transport by increased transferrin uptake. Downstream expression analysis of MYO5B mutants demonstrated a transcriptional activation of genes involved in glucose metabolism, proliferation, homeostasis, and migration. Our study validates the functional role of novel MYO5B mutations in proliferation and migration, and suggest the MYO5-pathway to be involved the malignant progression of PPGL tumors.","abstract":"Identification of additional cancer-associated genes and secondary mutations driving the metastatic progression in pheochromocytoma and paraganglioma (PPGL) is important. We recently reported novel recurrent nonsynonymous mutations in the MYO5B gene in metastatic PPGL. Here, we explored the functional impact of these MYO5B mutations, and analyzed MYO5B expression in primary PPGL tumor cases in relation to mutation status.Immunohistochemistry and mRNA expression analysis in 30 primary PPGL tumors revealed an increased MYO5B expression in metastatic compared to non-metastatic tumor cases. In addition, subcellular localization of MYO5B protein was altered from cytoplasmatic to membranous in some metastatic tumors, and the strongest and most abnormal expression pattern was observed in a PGL case harboring a MYO5B:p.G1611S mutation. Mutation analysis of additional PPGL tumors revealed additional, and hence recurrent, mutations in the paralog MYO5A. Three missense mutations in MYO5B were functionally studied using site directed mutagenesis and stable transfection into human neuroblastoma cells (SK-N-AS) and embryonic kidney cells (HEK293 cell line). Functional analysis of the mutants verified a significant increased proliferation rate in all MYO5B mutated clones (p.L587P,  p.G1611S, and p.R1641C).  The two somatically derived mutations p.L587P and p.G1611S were also found to increase the migration rate, and all three mutants affected intracellular transport by increased transferrin uptake. Downstream expression analysis of MYO5B mutants demonstrated a transcriptional activation of genes involved in glucose metabolism, proliferation, homeostasis, and migration. Our study validates the functional role of novel MYO5B mutations in proliferation and migration, and suggest the MYO5-pathway to be involved the malignant progression of PPGL tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-28T15:19:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003992","title":"Lindsey E. Jones et al.  Patient-derived cells from recurrent tumors that model the evolution of IDH-mutant glioma. Neuro-Oncology Advances, 2020. We established robust, versatile, and well-characterized Patient Derived Cells (PDC) of an IDH1-mutant astrocytoma and an IDH1-mutant oligodendroglioma that represents defined evolutionary stages of chemotherapy-induced hypermutation. The PDCs retain tumor subtype defining features over time as well as classic hallmarks of cancer, including anchorage independent growth and cell immortality. The integrated phylogenies composed of PDCs,single-cell-derived PDCs, patient-derived xenografts, and corresponding spatiotemporal tumor tissue samples also provide new insight into the clonality, evolutionary pattern, and immense mutational load of hypermutated IDH mutant gliomas.","description":"IDH-mutant lower-grade gliomas can undergo malignant progression via temozolomide-driven hypermutation. Patient-derived cells (PDC) that model the genetically distinct hypermutated (HM) tumor subgroup are generally lacking, and few if any human brain tumor cell models are from defined evolutionary time points. Here, we characterize multiple PDC derived from independent surgical specimens of IDH1-mutant recurrences, including an ATRX and TP53-mutant astrocytoma and a 1p/19q co-deleted and TERT promoter-mutant oligodendroglioma. We determined the evolutionary time points represented by each PDC using exome sequencing and phylogenetic reconstruction, comparing the PDC and single cell clones of the PDC (scPDC) to multiple spatiotemporal tumor tissue samples, PDC-derived xenografts (PDX) and patient-matched blood. The tumor samples exhibited TMZ-induced mutagenesis and a branching pattern of evolution. We found clear evidence of two fully independent founder HM clones in the tumor tissue that are faithfully represented by independent PDC. The PDC, scPDC and PDX also shared the mutagenesis signature and represent the mid and later evolutionary time points of their corresponding tumors. The PDC maintained the tumor subtype-defining features over many passages, including heterozygosity of the IDH1 R132H mutation, production of 2-hydroxyglutarate (2-HG), and subtype-specific telomere maintenance mechanisms. The PDC from both tumors exhibited anchorage-independent growth in soft agar. The oligodendroglioma PDC formed infiltrative intracranial tumors with characteristic oligodendroglioma histology, initially with a long period to tumor formation. We conclude that the PDC, scPDC and PDX faithfully model the heterogeneous clonal origins of the corresponding tumor tissue. The multilevel analysis also provides new insight into the intratumoral heterogeneity and vast mutational load of HM glioma. The PDC from multiple evolutionary time points presented in the context of full clinical timelines may be useful to model evolution and intratumoral heterogeneity, important sources of therapeutic failure.","abstract":"IDH-mutant lower-grade gliomas can undergo malignant progression via temozolomide-driven hypermutation. Patient-derived cells (PDC) that model the genetically distinct hypermutated (HM) tumor subgroup are generally lacking, and few if any human brain tumor cell models are from defined evolutionary time points. Here, we characterize multiple PDC derived from independent surgical specimens of IDH1-mutant recurrences, including an ATRX and TP53-mutant astrocytoma and a 1p/19q co-deleted and TERT promoter-mutant oligodendroglioma. We determined the evolutionary time points represented by each PDC using exome sequencing and phylogenetic reconstruction, comparing the PDC and single cell clones of the PDC (scPDC) to multiple spatiotemporal tumor tissue samples, PDC-derived xenografts (PDX) and patient-matched blood. The tumor samples exhibited TMZ-induced mutagenesis and a branching pattern of evolution. We found clear evidence of two fully independent founder HM clones in the tumor tissue that are faithfully represented by independent PDC. The PDC, scPDC and PDX also shared the mutagenesis signature and represent the mid and later evolutionary time points of their corresponding tumors. The PDC maintained the tumor subtype-defining features over many passages, including heterozygosity of the IDH1 R132H mutation, production of 2-hydroxyglutarate (2-HG), and subtype-specific telomere maintenance mechanisms. The PDC from both tumors exhibited anchorage-independent growth in soft agar. The oligodendroglioma PDC formed infiltrative intracranial tumors with characteristic oligodendroglioma histology, initially with a long period to tumor formation. We conclude that the PDC, scPDC and PDX faithfully model the heterogeneous clonal origins of the corresponding tumor tissue. The multilevel analysis also provides new insight into the intratumoral heterogeneity and vast mutational load of HM glioma. The PDC from multiple evolutionary time points presented in the context of full clinical timelines may be useful to model evolution and intratumoral heterogeneity, important sources of therapeutic failure.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-29T04:29:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003993","title":"Peripheral clonal expansion of T cells (scRNA-seq)","description":null,"abstract":"We performed single-cell RNA sequencing (scRNA-seq) and deep analysis of T cell receptor (TCR) clonotypes (scTCR-seq) in cancer patients across several indications, assessing the profiles of TCRs in the various populations of T cells in tumours, normal adjacent tissue (NAT), and peripheral blood.  In a subset of patients, we find clear evidence of clonotypic expansion of T effector-like cells not only within the tumour but also in NAT.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-29T07:02:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003994","title":"Peripheral clonal expansion of T cells (scTCR-seq)","description":null,"abstract":"We performed single-cell RNA sequencing (scRNA-seq) and deep analysis of T cell receptor (TCR) clonotypes (scTCR-seq) in cancer patients across several indications, assessing the profiles of TCRs in the various populations of T cells in tumours, normal adjacent tissue (NAT), and peripheral blood.  In a subset of patients, we find clear evidence of clonotypic expansion of T effector-like cells not only within the tumour but also in NAT.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-29T07:05:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003995","title":"NPC genetic susceptibility in MHC region","description":null,"abstract":"NPC genetic susceptibility in MHC region","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003996","title":"A spatiotemporal organ-wide gene expression and cell atlas of the developing human heart","description":"The process of cardiac morphogenesis in humans is incompletely understood. Its full characterization requires a deep exploration of the organ-wide orchestration of gene expression with a single-cell spatial resolution. Here, we present a molecular approach that reveals the comprehensive transcriptional landscape of cell types populating the embryonic heart at three developmental stages, and which maps cell type-specific gene expression to specific anatomical domains.\nSpatial Transcriptomics identified unique gene profiles corresponding to distinct anatomical regions in each developmental stage. Human embryonic cardiac cell types identified by single-cell RNA-sequencing confirmed and enriched the spatial annotation of embryonic cardiac gene expression. In situ sequencing was then used to refine these results and create spatial subcellular map for the three developmental phases. Finally, we generated a publicly available web resource of the human developing heart to facilitate future studies on human cardiogenesis.","abstract":"The process of cardiac morphogenesis in humans is incompletely understood. Its full characterization requires a deep exploration of the organ-wide orchestration of gene expression with a single-cell spatial resolution. Here, we present a molecular approach that reveals the comprehensive transcriptional landscape of cell types populating the embryonic heart at three developmental stages, and which maps cell type-specific gene expression to specific anatomical domains.\nSpatial Transcriptomics identified unique gene profiles corresponding to distinct anatomical regions in each developmental stage. Human embryonic cardiac cell types identified by single-cell RNA-sequencing confirmed and enriched the spatial annotation of embryonic cardiac gene expression. In situ sequencing was then used to refine these results and create spatial subcellular map for the three developmental phases. Finally, we generated a publicly available web resource of the human developing heart to facilitate future studies on human cardiogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-29T15:59:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003997","title":"InsPIRE islets","description":"We explored the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using RNA-Seq and genotyping data from 420 islet donors and 26 FAC sorted beta-cells.","abstract":"We explored the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using RNA-Seq and genotyping data from 420 islet donors and 26 FAC sorted beta-cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-30T13:09:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001003998","title":"HCA_WSSS_Adult_Lung_RNA","description":"WSSS Deep Dive for Adult Lung RNA only.  This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/\n\nHuman Cell Atlas for lung - Adult RNA work. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"WSSS Deep Dive for Adult Lung RNA only.  This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/\n\nHuman Cell Atlas for lung - Adult RNA work. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001003999","title":"Myeloma RNAseq","description":null,"abstract":"Most patients with multiple myeloma (MM) die from progressive disease after relapse. To advance our understanding of MM evolution mechanisms, we performed whole-genome sequencing of 80 tumour-normal newly diagnosed pairs and 25 matched relapse tumours from the Myeloma XI trial.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-31T12:19:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004000","title":"Myeloma WGS","description":"Most patients with multiple myeloma (MM) die from progressive disease after relapse. To advance our understanding of MM evolution mechanisms, we performed whole-genome sequencing of 80 tumour-normal newly diagnosed pairs and 24 matched relapse tumours from the Myeloma XI trial.","abstract":"Most patients with multiple myeloma (MM) die from progressive disease after relapse. To advance our understanding of MM evolution mechanisms, we performed whole-genome sequencing of 80 tumour-normal newly diagnosed pairs and 24 matched relapse tumours from the Myeloma XI trial.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-10-31T11:19:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004001","title":"Tumor-specific expression of let-7i and miR-192 is associated with resistance to cisplatin-based chemoradiotherapy in patients with larynx and hypopharynx cancer","description":"Background: The majority of patients with locally advanced larynx or hypopharynx squamous cell carcinoma are treated with organ preserving chemoradiotherapy (CRT). Clinical outcome following CRT varies greatly. We hypothesized tumor microRNA (miRNA) expression is predictive for outcome following CRT. Methods: Next-generation sequencing (NGS) miRNA profiling was performed on 37 formalin fixed paraffin embedded (FFPE) tumor samples. Patients with a recurrence free survival (RFS) of less than 2 years (“poor  outcome”) and patients without recurrence within 2 years (“good outcome”) were compared by differential expression analysis. Tumor-specific miRNAs were selected based on normal mucosa miRNA expression data from The Cancer Genome Atlas database. A model was constructed to predict outcome using group-regularized penalized logistic ridge regression. Candidate miRNAs were validated in the initial sample set by RT-qPCR as well as in 46 additional tumor samples.Results: 1,938 known mature miRNAs were detected. Thirteen miRNAs were differentially expressed (p&lt;0.05, FDR&lt;0.1) according to outcome group. Initial class prediction in the NGS cohort (n=37) resulted in a model combining five miRNAs and disease stage, able to predict CRT outcome with an area under the curve (AUC) of 0.82. In the RT-qPCR cohort (n=83), 25 patients (30%) experienced early recurrence (median RFS 8 months; median follow-up 42 months). Class prediction resulted in a model combining let-7i-5p and miR-192-5p and disease stage, able to discriminate with an AUC of 0.80 patients with good versus poor clinical outcome.Conclusion: The combined miRNA expression and disease stage prediction model is superior to using either factor alone. ¬¬¬This study indicates NGS miRNA profiling using FFPE specimens is feasible, resulting in clinically relevant biomarkers.","abstract":"Background: The majority of patients with locally advanced larynx or hypopharynx squamous cell carcinoma are treated with organ preserving chemoradiotherapy (CRT). Clinical outcome following CRT varies greatly. We hypothesized tumor microRNA (miRNA) expression is predictive for outcome following CRT. Methods: Next-generation sequencing (NGS) miRNA profiling was performed on 37 formalin fixed paraffin embedded (FFPE) tumor samples. Patients with a recurrence free survival (RFS) of less than 2 years (“poor  outcome”) and patients without recurrence within 2 years (“good outcome”) were compared by differential expression analysis. Tumor-specific miRNAs were selected based on normal mucosa miRNA expression data from The Cancer Genome Atlas database. A model was constructed to predict outcome using group-regularized penalized logistic ridge regression. Candidate miRNAs were validated in the initial sample set by RT-qPCR as well as in 46 additional tumor samples.Results: 1,938 known mature miRNAs were detected. Thirteen miRNAs were differentially expressed (p&lt;0.05, FDR&lt;0.1) according to outcome group. Initial class prediction in the NGS cohort (n=37) resulted in a model combining five miRNAs and disease stage, able to predict CRT outcome with an area under the curve (AUC) of 0.82. In the RT-qPCR cohort (n=83), 25 patients (30%) experienced early recurrence (median RFS 8 months; median follow-up 42 months). Class prediction resulted in a model combining let-7i-5p and miR-192-5p and disease stage, able to discriminate with an AUC of 0.80 patients with good versus poor clinical outcome.Conclusion: The combined miRNA expression and disease stage prediction model is superior to using either factor alone. ¬¬¬This study indicates NGS miRNA profiling using FFPE specimens is feasible, resulting in clinically relevant biomarkers.","study_type":"Other","pubmed_ids":[32585557],"external_links":null,"is_released":true,"released_date":"2019-11-01T10:22:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004002","title":"Discovering genetic causes of optic atrophy syndromes through whole exome sequencing","description":null,"abstract":"WES was performed in patients with optic atrophy to identify the causative genetic defect","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004003","title":"SSBP1","description":"SSBP1 mutations cause a complex optic atrophy spectrum disorder with mitochondrial DNA depletion","abstract":"SSBP1 mutations cause a complex optic atrophy spectrum disorder with mitochondrial DNA depletion","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-02T11:31:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004004","title":"Human_Brain_Zika_Infection_Single_Cell_Analysis","description":"We wish to establish the selectivity of Zika Virus for infection of human brain and brain tumour cells using NGS techniques. Human primary cells obtained from patients undergoing brain tumour surgery  and embryonic brain specimens will be infected by Harry Bulstrode in University of Cambridge Department of Virology facilities with Zika Virus, wildtype or mCherry reporter derivative. In the latter case they will subsequently also undergo flow sorting. Afterwards, the cells will be lysed or cell nuclei will be extracted for single cell/nucleus sequencing. These elements will be undertaken by Harry Bulstrode using his established grant funding, ethics permissions and risk assessments. Acellularized samples will then be trasferred to Sanger for seqeuncing using thee 10X, NEB or other workflows.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We wish to establish the selectivity of Zika Virus for infection of human brain and brain tumour cells using NGS techniques. Human primary cells obtained from patients undergoing brain tumour surgery  and embryonic brain specimens will be infected by Harry Bulstrode in University of Cambridge Department of Virology facilities with Zika Virus, wildtype or mCherry reporter derivative. In the latter case they will subsequently also undergo flow sorting. Afterwards, the cells will be lysed or cell nuclei will be extracted for single cell/nucleus sequencing. These elements will be undertaken by Harry Bulstrode using his established grant funding, ethics permissions and risk assessments. Acellularized samples will then be trasferred to Sanger for seqeuncing using thee 10X, NEB or other workflows.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004005","title":"Genomic and immune profiling of pre-invasive lung adenocarcinoma","description":null,"abstract":"Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004006","title":"Genomic and immune profiling of pre-invasive lung adenocarcinoma","description":"Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.","abstract":"Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-04T17:35:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004007","title":"Whole-genome sequencing of normal Singaporean volunteers","description":"Sleep is associated with various health outcomes. Despite their growing adoption, the potential for consumer wearables to contribute sleep metrics to sleep-related biomedical research remains largely uncharacterized. Here we analyzed sleep tracking data, along with questionnaire responses and multi-modal phenotypic data generated from 482 normal volunteers. First, we compared wearable-derived and self-reported sleep metrics, particularly total sleep time (TST) and sleep efficiency (SE). We then identified demographic, socioeconomic and lifestyle factors associated with wearable-derived TST. Among others, male gender (β = -15.539, 95% confidence interval [CI] = -26.245 - -4.832, p = 0.005), older age (β = -0.493, CI = -0.941 - -0.044, p = 0.032) and manual labor (β = -26.856, CI = -49.715 - -3.997, p = 0.022) were associated with reduced TST, whereas alcohol consumption (β = 19.247, CI = 8.008 - 30.486, p = 8.54x10-04) was associated with increased TST. Multi-modal phenotypic data analysis showed that wearable-derived TST and SE were associated with various cardiovascular disease risk markers such as body mass index (β = -0.006, CI = -0.00 - -0.000, p = 0.040) and waist circumference (β = 0.001, CI = -0.015-0.017, p = 0.893), whereas self-reported measures were not. We then showed that insufficient sleep was associated with premature telomere attrition, using telomere length estimated using whole-genome sequencing (β = 1.275, CI = 0.187 - 2.363, p = 0.023) and quantitative PCR (β = 0.001, CI = 8.318x10-05 - 0.001, p = 0.028). Our study highlights the potential for sleep metrics from consumer wearables to provide novel insights into data generated from population cohort studies.","abstract":"Sleep is associated with various health outcomes. Despite their growing adoption, the potential for consumer wearables to contribute sleep metrics to sleep-related biomedical research remains largely uncharacterized. Here we analyzed sleep tracking data, along with questionnaire responses and multi-modal phenotypic data generated from 482 normal volunteers. First, we compared wearable-derived and self-reported sleep metrics, particularly total sleep time (TST) and sleep efficiency (SE). We then identified demographic, socioeconomic and lifestyle factors associated with wearable-derived TST. Among others, male gender (β = -15.539, 95% confidence interval [CI] = -26.245 - -4.832, p = 0.005), older age (β = -0.493, CI = -0.941 - -0.044, p = 0.032) and manual labor (β = -26.856, CI = -49.715 - -3.997, p = 0.022) were associated with reduced TST, whereas alcohol consumption (β = 19.247, CI = 8.008 - 30.486, p = 8.54x10-04) was associated with increased TST. Multi-modal phenotypic data analysis showed that wearable-derived TST and SE were associated with various cardiovascular disease risk markers such as body mass index (β = -0.006, CI = -0.00 - -0.000, p = 0.040) and waist circumference (β = 0.001, CI = -0.015-0.017, p = 0.893), whereas self-reported measures were not. We then showed that insufficient sleep was associated with premature telomere attrition, using telomere length estimated using whole-genome sequencing (β = 1.275, CI = 0.187 - 2.363, p = 0.023) and quantitative PCR (β = 0.001, CI = 8.318x10-05 - 0.001, p = 0.028). Our study highlights the potential for sleep metrics from consumer wearables to provide novel insights into data generated from population cohort studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-04T19:03:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004008","title":"Single cell RNAseq of PBMC from bladder cancer patients","description":"Frozen PBMC samples containing at least 1 million cells were thawed for 1 minute at 37C and washed twice with RPMI complete media (10% FBS with glutamate and Pen/Strep). All of the samples had &gt;80% viable cells. Sample processing for single-cell RNA-seq was done using Chromium Single Cell 3’ Library and Gel bead kit v2 (PN-120237) following manufacturer’s user guide (CG00052, 10x Genomics, Pleasanton, CA). The total cell density was used to impute the volume of single cell suspension needed in the reverse transcription (RT) master mix, aiming to achieve ~ 6,000 cells per sample. cDNAs and libraries were prepared following manufacturer’s user guide (10x Genomics). cDNA amplification and indexed libraries were prepared using 12 and 14 cycles of PCR, respectively. Libraries were profiled, quantified, and sequenced as 5’ single-cell gene expression libraries.","abstract":"Frozen PBMC samples containing at least 1 million cells were thawed for 1 minute at 37C and washed twice with RPMI complete media (10% FBS with glutamate and Pen/Strep). All of the samples had &gt;80% viable cells. Sample processing for single-cell RNA-seq was done using Chromium Single Cell 3’ Library and Gel bead kit v2 (PN-120237) following manufacturer’s user guide (CG00052, 10x Genomics, Pleasanton, CA). The total cell density was used to impute the volume of single cell suspension needed in the reverse transcription (RT) master mix, aiming to achieve ~ 6,000 cells per sample. cDNAs and libraries were prepared following manufacturer’s user guide (10x Genomics). cDNA amplification and indexed libraries were prepared using 12 and 14 cycles of PCR, respectively. Libraries were profiled, quantified, and sequenced as 5’ single-cell gene expression libraries.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-04T19:16:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004009","title":"Spontaneous mutations in the single TTN gene represent high tumor mutation burden","description":"Tumor mutation burden (TMB) is an emerging biomarker, whose calculation requires targeted sequencing of many genes. We investigated if the measurement of mutation counts within a single gene is representative of TMB. Whole exome sequencing (WES) data from the pan-cancer cohort (n=10,224) of TCGA, and targeted sequencing (tNGS) and TTN gene sequencing from 24 colorectal cancer samples (AMC cohort) were analyzed.","abstract":"Tumor mutation burden (TMB) is an emerging biomarker, whose calculation requires targeted sequencing of many genes. We investigated if the measurement of mutation counts within a single gene is representative of TMB. Whole exome sequencing (WES) data from the pan-cancer cohort (n=10,224) of TCGA, and targeted sequencing (tNGS) and TTN gene sequencing from 24 colorectal cancer samples (AMC cohort) were analyzed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-05T06:09:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004010","title":"RNAseq_iho_lk4","description":"The aim of this project is to meausre the host transcriptional response to bacterial toxins and whole bacteria to compare against naïve cells. The cells being used will be small intestinal organoids derived from the cell line Kolf-2.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We will analyse transcriptomic data from naïve, toxin treated and bacterial infected cells.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004011","title":"Berlin Neuroblastoma Cohort","description":null,"abstract":"Matched tumor-normal whole-genome sequencing and tumor RNA-seq of primary neuroblastoma samples.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004012","title":"Familial adult myoclonic epilepsy in Sri Lankan and Indian families","description":"Familial adult myoclonic epilepsy 1 (FAME1), first recognised in Japanese families, was recently shown to be caused by a TTTCA repeat insertion in intron 4 of SAMD12 on chromosome 8. We performed whole genome sequencing on two families with FAME, one of Sri Lankan origin and the other of Indian origin, and identified a TTTCA repeat insertion in SAMD12 in both families. Haplotype analysis revealed that both families shared the same core ancestral haplotype reported in Japanese and Chinese families with FAME1. Mutation dating, based on the length of shared haplotypes, estimated the age of the ancestral haplotype to be approximately 670 generations, or 17,000 years old. Our data extend the geographic range of this repeat expansion to Southern Asia and potentially implicate an even broader regional distribution given the age of the variant. This finding suggests patients of Asian ancestry with suspected FAME should be screened for the SAMD12 TTTCA expansion.","abstract":"Familial adult myoclonic epilepsy 1 (FAME1), first recognised in Japanese families, was recently shown to be caused by a TTTCA repeat insertion in intron 4 of SAMD12 on chromosome 8. We performed whole genome sequencing on two families with FAME, one of Sri Lankan origin and the other of Indian origin, and identified a TTTCA repeat insertion in SAMD12 in both families. Haplotype analysis revealed that both families shared the same core ancestral haplotype reported in Japanese and Chinese families with FAME1. Mutation dating, based on the length of shared haplotypes, estimated the age of the ancestral haplotype to be approximately 670 generations, or 17,000 years old. Our data extend the geographic range of this repeat expansion to Southern Asia and potentially implicate an even broader regional distribution given the age of the variant. This finding suggests patients of Asian ancestry with suspected FAME should be screened for the SAMD12 TTTCA expansion.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-06T10:30:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004013","title":"Whole genome, exome and transcriptome analysis to guide individualized cancer interpretation","description":"Study Design: The Cancer Alliance study was a collaboration of nine academic medical institutions in the New York city area and led by the New York Genome Center.  Tumor-normal paired samples were submitted by the institutions for whole genome, whole exome and transcriptome sequencing and bioinformatics analysis at New York Genome Center. Relevant clinical histories were also collected. Raw sequence files were available to all collaborators.  Variant call files were analyzed both manually by interpreters at NYGC and by IBM Watson Genome Analytics.  This study was approved by a central institutional review board (IRB), Biomedical Research Alliance of New York, and by local IRBs, including Stony Brook University and Northwell Health. The study was supported in part by a grant from the IBM corporation (IBM Watson Health) to the New York Genome Center, New York Genome Center philanthropic funds and Rockefeller University grant # UL1TR000043 from the National Center for Advancing Translational Sciences (NCATS), and the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program. The principal investigator Robert B. Darnell MD, PhD., is a Howard Hughes Medical Institute Investigator.\n \nResults: Pending Publication of Analysis of Study\n \nConclusions: Pending Publication of Analysis of Study","abstract":"Study Design: The Cancer Alliance study was a collaboration of nine academic medical institutions in the New York city area and led by the New York Genome Center.  Tumor-normal paired samples were submitted by the institutions for whole genome, whole exome and transcriptome sequencing and bioinformatics analysis at New York Genome Center. Relevant clinical histories were also collected. Raw sequence files were available to all collaborators.  Variant call files were analyzed both manually by interpreters at NYGC and by IBM Watson Genome Analytics.  This study was approved by a central institutional review board (IRB), Biomedical Research Alliance of New York, and by local IRBs, including Stony Brook University and Northwell Health. The study was supported in part by a grant from the IBM corporation (IBM Watson Health) to the New York Genome Center, New York Genome Center philanthropic funds and Rockefeller University grant # UL1TR000043 from the National Center for Advancing Translational Sciences (NCATS), and the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program. The principal investigator Robert B. Darnell MD, PhD., is a Howard Hughes Medical Institute Investigator.\n \nResults: Pending Publication of Analysis of Study\n \nConclusions: Pending Publication of Analysis of Study","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-06T10:42:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004014","title":"Mapping the breast cancer metastatic cascade onto circulating tumour DNA using genetic and epigenetic clonal tracking","description":"Circulating tumour DNA (ctDNA) allows tracking the evolution of human cancers at high resolution, overcoming many limitations of tissue biopsies. However, exploiting ctDNA to determine how a patient’s cancer is evolving in order to aid clinical decisions remains difficult. This is because ctDNA is a mix of fragmented alleles, and the contribution of different cancer cell subpopulations from distinct lesions to ctDNA remains largely unknown. Profiling of ctDNA almost invariably requires prior knowledge of what genomic alterations to track. Here we leverage on a rapid autopsy programme to demonstrate that unbiased genomic characterisation of several metastatic sites and concomitant ctDNA profiling at whole-genome resolution reveals the extent to which ctDNA is representative of widespread disease. We also present a ctDNA methylation profiling method that allows tracking evolutionary changes in the cancer cell population at single-molecule resolution without prior knowledge. These results have critical implications for the use of liquid biopsies to monitor cancer evolution in humans and potentially guide treatment.","abstract":"Circulating tumour DNA (ctDNA) allows tracking the evolution of human cancers at high resolution, overcoming many limitations of tissue biopsies. However, exploiting ctDNA to determine how a patient’s cancer is evolving in order to aid clinical decisions remains difficult. This is because ctDNA is a mix of fragmented alleles, and the contribution of different cancer cell subpopulations from distinct lesions to ctDNA remains largely unknown. Profiling of ctDNA almost invariably requires prior knowledge of what genomic alterations to track. Here we leverage on a rapid autopsy programme to demonstrate that unbiased genomic characterisation of several metastatic sites and concomitant ctDNA profiling at whole-genome resolution reveals the extent to which ctDNA is representative of widespread disease. We also present a ctDNA methylation profiling method that allows tracking evolutionary changes in the cancer cell population at single-molecule resolution without prior knowledge. These results have critical implications for the use of liquid biopsies to monitor cancer evolution in humans and potentially guide treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-06T16:43:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004015","title":"Reconstruction of complex rearrangement patterns causing the initiation of clear cell renal cell carcinoma.","description":"The genomic hallmark of clear cell renal cell carcinoma is the loss of the short arm of chromosome three. This appears to be the earliest genomic event in the formation of these cancers. Often chromosome 3 is lost at the same time as part of chromosome 5 is duplicated via an unbalanced translocation, often with features consistent with focal chromothripsis. In this study, we sought to reconstruct the chromothriptic event that underlies the initiation of kidney cancer. We used long read sequencing (promethION, Oxford Nanopore Technologies) of patient tumour-derived DNA to elucidate how a single cell division error can generate cancer genome complexity.","abstract":"The genomic hallmark of clear cell renal cell carcinoma is the loss of the short arm of chromosome three. This appears to be the earliest genomic event in the formation of these cancers. Often chromosome 3 is lost at the same time as part of chromosome 5 is duplicated via an unbalanced translocation, often with features consistent with focal chromothripsis. In this study, we sought to reconstruct the chromothriptic event that underlies the initiation of kidney cancer. We used long read sequencing (promethION, Oxford Nanopore Technologies) of patient tumour-derived DNA to elucidate how a single cell division error can generate cancer genome complexity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-06T17:03:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004016","title":"Epigenomic data of HEMa_LP","description":"To profile the epigenomic landscape of  Human Epidermal Melanocytes , adult, lightly pigmented(HEMa-LP), whole genome bisulphite sequencing (WGBS) and ChIP-seq of histone marks data were generated.","abstract":"To profile the epigenomic landscape of  Human Epidermal Melanocytes , adult, lightly pigmented(HEMa-LP), whole genome bisulphite sequencing (WGBS) and ChIP-seq of histone marks data were generated.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-07T03:40:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004017","title":"A Protein Neddylation Inhibitor MLN4924 Suppresses Patient-Derived Glioblastoma Cells via Inhibition of ERK and AKT Signaling","description":"Glioblastoma is a highly aggressive and lethal brain tumor, with limited treatment options. Abnormal activation of the neddylation pathway is observed in glioblastoma, and the NEDD8-activating enzyme (NAE) inhibitor, MLN4924 was previously shown to be effective in glioblastoma cell line models. However, its effect has not been tested in patient-derived glioblastoma stem cells. Immunohistochemistry and public data were analyzed to determine whether NEDD8 pathway proteins are important in glioblastoma development and patient survival. The effects of MLN4924 were evaluated in 4 glioblastoma cell lines and 15 patient-derived glioblastoma stem cells using high content analysis. Immunoblot analysis assessed the NEDD8 pathway proteins and biomarkers. Whole transcriptome analysis identified pathways associated with MLN4924 sensitivity. NAE1 and UBA3 levels increased in glioblastoma patients; high NEDD8 levels were associated with poor clinical outcomes. Glioblastoma cell lines and patient-derived stem cells were highly susceptible to MLN4924, while normal human astrocytes were resistant. Genomic analyses indicated that MLN4924 sensitive cells exhibited enrichment of ERK and AKT signaling. We verified that MLN4924 inhibits ERK and AKT phosphorylation in MLN4924 sensitive cells. Our findings suggest that patient-derived glioblastoma stem cells in the context of ERK and AKT activation are sensitive and highly regulated by neddylation inhibition.","abstract":"Glioblastoma is a highly aggressive and lethal brain tumor, with limited treatment options. Abnormal activation of the neddylation pathway is observed in glioblastoma, and the NEDD8-activating enzyme (NAE) inhibitor, MLN4924 was previously shown to be effective in glioblastoma cell line models. However, its effect has not been tested in patient-derived glioblastoma stem cells. Immunohistochemistry and public data were analyzed to determine whether NEDD8 pathway proteins are important in glioblastoma development and patient survival. The effects of MLN4924 were evaluated in 4 glioblastoma cell lines and 15 patient-derived glioblastoma stem cells using high content analysis. Immunoblot analysis assessed the NEDD8 pathway proteins and biomarkers. Whole transcriptome analysis identified pathways associated with MLN4924 sensitivity. NAE1 and UBA3 levels increased in glioblastoma patients; high NEDD8 levels were associated with poor clinical outcomes. Glioblastoma cell lines and patient-derived stem cells were highly susceptible to MLN4924, while normal human astrocytes were resistant. Genomic analyses indicated that MLN4924 sensitive cells exhibited enrichment of ERK and AKT signaling. We verified that MLN4924 inhibits ERK and AKT phosphorylation in MLN4924 sensitive cells. Our findings suggest that patient-derived glioblastoma stem cells in the context of ERK and AKT activation are sensitive and highly regulated by neddylation inhibition.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004018","title":"A Protein Neddylation Inhibitor MLN4924 Suppresses Patient-Derived Glioblastoma Cells via Inhibition of ERK and AKT Signaling","description":"Glioblastoma is a highly aggressive and lethal brain tumor, with limited treatment options. Abnormal activation of the neddylation pathway is observed in glioblastoma, and the NEDD8-activating enzyme (NAE) inhibitor, MLN4924 was previously shown to be effective in glioblastoma cell line models. However, its effect has not been tested in patient-derived glioblastoma stem cells. Immunohistochemistry and public data were analyzed to determine whether NEDD8 pathway proteins are important in glioblastoma development and patient survival. The effects of MLN4924 were evaluated in 4 glioblastoma cell lines and 15 patient-derived glioblastoma stem cells using high content analysis. Immunoblot analysis assessed the NEDD8 pathway proteins and biomarkers. Whole transcriptome analysis identified pathways associated with MLN4924 sensitivity. NAE1 and UBA3 levels increased in glioblastoma patients; high NEDD8 levels were associated with poor clinical outcomes. Glioblastoma cell lines and patient-derived stem cells were highly susceptible to MLN4924, while normal human astrocytes were resistant. Genomic analyses indicated that MLN4924 sensitive cells exhibited enrichment of ERK and AKT signaling. We verified that MLN4924 inhibits ERK and AKT phosphorylation in MLN4924 sensitive cells. Our findings suggest that patient-derived glioblastoma stem cells in the context of ERK and AKT activation are sensitive and highly regulated by neddylation inhibition.","abstract":"Glioblastoma is a highly aggressive and lethal brain tumor, with limited treatment options. Abnormal activation of the neddylation pathway is observed in glioblastoma, and the NEDD8-activating enzyme (NAE) inhibitor, MLN4924 was previously shown to be effective in glioblastoma cell line models. However, its effect has not been tested in patient-derived glioblastoma stem cells. Immunohistochemistry and public data were analyzed to determine whether NEDD8 pathway proteins are important in glioblastoma development and patient survival. The effects of MLN4924 were evaluated in 4 glioblastoma cell lines and 15 patient-derived glioblastoma stem cells using high content analysis. Immunoblot analysis assessed the NEDD8 pathway proteins and biomarkers. Whole transcriptome analysis identified pathways associated with MLN4924 sensitivity. NAE1 and UBA3 levels increased in glioblastoma patients; high NEDD8 levels were associated with poor clinical outcomes. Glioblastoma cell lines and patient-derived stem cells were highly susceptible to MLN4924, while normal human astrocytes were resistant. Genomic analyses indicated that MLN4924 sensitive cells exhibited enrichment of ERK and AKT signaling. We verified that MLN4924 inhibits ERK and AKT phosphorylation in MLN4924 sensitive cells. Our findings suggest that patient-derived glioblastoma stem cells in the context of ERK and AKT activation are sensitive and highly regulated by neddylation inhibition.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-08T07:26:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004019","title":"Whole-genome bisulfite sequencing analysis of low-grade astrocytomas in the ICGC PedBrain Tumor Project","description":"Pilocytic Astrocytoma (PA) is the most common pediatric brain tumor. While genome and transcriptome landscapes are well-studied, data of the complete methylome, tumor cell composition and immune infiltration are scarce. We generated whole genome bisulfite sequence data (WGBS) of nine PAs to find evidence for a link of focal methylation differences and differential gene expression to immune infiltration.","abstract":"Pilocytic Astrocytoma (PA) is the most common pediatric brain tumor. While genome and transcriptome landscapes are well-studied, data of the complete methylome, tumor cell composition and immune infiltration are scarce. We generated whole genome bisulfite sequence data (WGBS) of nine PAs to find evidence for a link of focal methylation differences and differential gene expression to immune infiltration.","study_type":"Other","pubmed_ids":[32052037],"external_links":null,"is_released":true,"released_date":"2019-11-08T15:26:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004020","title":"Uncovering tumor intrinsic and extrinsic factors that regulate hepatocellular carcinoma growth using patient derived xenograft assays","description":"Several major factors limit our understanding of hepatocellular carcinoma (HCC). First, human HCCs are infrequently biopsied for diagnosis and thus are not often biologically interrogated. Second, HCC initiation and progression are strongly influenced by the cirrhotic microenvironment, and the exact contributions of intrinsic and extrinsic tumor factors are unclear. A powerful approach to examine the personalized biology of liver cancers and the influence of host tissues is with patient derived xenograft (PDX) models. In Asia, HCCs from hepatitis B virus patients have been efficiently converted into PDXs, but few parallel efforts from the west have been reported. In a large-scale analysis, we implanted 93 HCCs and 8 cholangiocarcinomas (CCAs) to systematically analyze host factors and to define an optimized platform for PDX development from both surgical and biopsy samples. NSG mice that had undergone partial hepatectomy (PHx) represented the best combination of engraftability, growth, and passageability, but overall rates were low and indicative of a unique intrinsic biology for HCCs in the US. PDX models preserved the histology and genetic features of parental tumors, and ultimately, 9 new models were usable for pre-clinical studies. Intriguingly, HCC PDXs were differentially sensitive to regorafenib and sorafenib and CCA PDXs were also highly sensitive to regorafenib. PDX models functionalize early and advanced stage HCCs and revealed unique biological features of liver cancers from the US.","abstract":"Several major factors limit our understanding of hepatocellular carcinoma (HCC). First, human HCCs are infrequently biopsied for diagnosis and thus are not often biologically interrogated. Second, HCC initiation and progression are strongly influenced by the cirrhotic microenvironment, and the exact contributions of intrinsic and extrinsic tumor factors are unclear. A powerful approach to examine the personalized biology of liver cancers and the influence of host tissues is with patient derived xenograft (PDX) models. In Asia, HCCs from hepatitis B virus patients have been efficiently converted into PDXs, but few parallel efforts from the west have been reported. In a large-scale analysis, we implanted 93 HCCs and 8 cholangiocarcinomas (CCAs) to systematically analyze host factors and to define an optimized platform for PDX development from both surgical and biopsy samples. NSG mice that had undergone partial hepatectomy (PHx) represented the best combination of engraftability, growth, and passageability, but overall rates were low and indicative of a unique intrinsic biology for HCCs in the US. PDX models preserved the histology and genetic features of parental tumors, and ultimately, 9 new models were usable for pre-clinical studies. Intriguingly, HCC PDXs were differentially sensitive to regorafenib and sorafenib and CCA PDXs were also highly sensitive to regorafenib. PDX models functionalize early and advanced stage HCCs and revealed unique biological features of liver cancers from the US.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-08T21:46:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004021","title":"Pancreatic cancer, which named the king of cancers, ranked as one of the top leading cause of cancer death worldwide, with a very low 5-year survival rate of only 25%. We performed multi-regional sampling for a total of 8 PDA patients (stage II), generating high quality single-cell multi-omic profiles.","description":"Pancreatic cancer, which named the king of cancers, ranked as one of the top leading cause of cancer death worldwide, with a very low 5-year survival rate of only 25%. We performed multi-regional sampling for a total of 8 PDA patients (stage II), generating high quality single-cell multi-omic profiles.","abstract":"Pancreatic cancer, which named the king of cancers, ranked as one of the top leading cause of cancer death worldwide, with a very low 5-year survival rate of only 25%. We performed multi-regional sampling for a total of 8 PDA patients (stage II), generating high quality single-cell multi-omic profiles.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004022","title":"Berlin Neuroblastoma Dataset","description":null,"abstract":"Paired RNA-seq and tumor/normal whole-genome sequencing of primary neuroblastoma","study_type":"Cancer Genomics","pubmed_ids":[37402719],"external_links":null,"is_released":true,"released_date":"2019-11-09T19:27:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004023","title":"Multi-regional tumour biopsies of a RET fusion patient","description":"Identifying modes of resistance to a new experimental drug for a patient resistant to other therapies","abstract":"Identifying modes of resistance to a new experimental drug for a patient resistant to other therapies","study_type":"Other","pubmed_ids":[31988000],"external_links":null,"is_released":true,"released_date":"2019-11-11T00:40:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004024","title":"HSC_population_dynamics__scRNA_seq___KX007","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004025","title":"HCA_Thymus_Disease_DiGeorge_Transplant_RNA","description":"Single cell transcriptomics study of thymic transplant biopsies \n\nAllogeneic thymus transplantation is the only curative therapy for complete DiGeorge Syndrome (cDGS), a rare severe primary immunodeficiency characterised by athymia.  GOSH is one of only two centres worldwide to offer this treatment. Despite a lack of major histocompatibility complex (MHC)-matching between donor and host, transplanted thymus becomes repopulated by recipient bone marrow derived precursor cells and supports development of functional T-cells. The mechanisms underlying thymopoiesis in this context are poorly understood, but over time we observe reconstitution of T-cell immunity, with the ability to produce host naïve T-cells showing a broad T-cell receptor (TCR) repertoire and to generate MHC-restricted T-cell proliferative responses. Although lifesaving, the achieved immunological reconstitution is typically not complete with circulating T-cell numbers usually remaining below the age related normal ranges. Additionally, we observe persistence of donor-derived T-cells of unknown clinical significance. To gain more insight into the mechanisms by which MHC-mismatched transplanted thymus supports T-cell development with self-tolerance, as well as into the basis of suboptimal T-cell immunity, we now aim to investigate immune reconstitution after thymus transplantation in further detail by using single-cell transcriptomics, applied to thymic transplant biopsies and peripheral blood samples collected during standard post-transplant patient care. By identifying which lineages of host- derived cells repopulate the thymic tissue after transplantation, we will be able to address the role of MHC in positive and negative T-cell selection during T-cell differentiation. We will also be able to clarify the exact ontogeny of the persistent donor T-cells, as well as their possible role. Understanding the mechanisms of action of HLA-mismatched transplanted thymus will contribute to treatment optimisation. Additionally, our research provides a unique opportunity to further investigate key immunological concepts, such as tolerance and autoimmunity, challenging existing paradigms in thymus immunology.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Single cell transcriptomics study of thymic transplant biopsies \n\nAllogeneic thymus transplantation is the only curative therapy for complete DiGeorge Syndrome (cDGS), a rare severe primary immunodeficiency characterised by athymia.  GOSH is one of only two centres worldwide to offer this treatment. Despite a lack of major histocompatibility complex (MHC)-matching between donor and host, transplanted thymus becomes repopulated by recipient bone marrow derived precursor cells and supports development of functional T-cells. The mechanisms underlying thymopoiesis in this context are poorly understood, but over time we observe reconstitution of T-cell immunity, with the ability to produce host naïve T-cells showing a broad T-cell receptor (TCR) repertoire and to generate MHC-restricted T-cell proliferative responses. Although lifesaving, the achieved immunological reconstitution is typically not complete with circulating T-cell numbers usually remaining below the age related normal ranges. Additionally, we observe persistence of donor-derived T-cells of unknown clinical significance. To gain more insight into the mechanisms by which MHC-mismatched transplanted thymus supports T-cell development with self-tolerance, as well as into the basis of suboptimal T-cell immunity, we now aim to investigate immune reconstitution after thymus transplantation in further detail by using single-cell transcriptomics, applied to thymic transplant biopsies and peripheral blood samples collected during standard post-transplant patient care. By identifying which lineages of host- derived cells repopulate the thymic tissue after transplantation, we will be able to address the role of MHC in positive and negative T-cell selection during T-cell differentiation. We will also be able to clarify the exact ontogeny of the persistent donor T-cells, as well as their possible role. Understanding the mechanisms of action of HLA-mismatched transplanted thymus will contribute to treatment optimisation. Additionally, our research provides a unique opportunity to further investigate key immunological concepts, such as tolerance and autoimmunity, challenging existing paradigms in thymus immunology.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-13T09:39:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004026","title":"Whole exome sequencing from early stage non-small cell lung cancer patients at MDACC","description":"The purpose of the study is to evaluate the mutational landscape and tumor mutational burden in tumor from patients with early stage non-small cell lung cancer. Mutational landscape was compared to the T cell repertoire to determine the relationship between somatic mutations and T cell response in early-stage NSCLC.","abstract":"The purpose of the study is to evaluate the mutational landscape and tumor mutational burden in tumor from patients with early stage non-small cell lung cancer. Mutational landscape was compared to the T cell repertoire to determine the relationship between somatic mutations and T cell response in early-stage NSCLC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-13T20:42:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004027","title":"Tumor intrinsic and extrinsic mechanisms of response and resistance to blinatumomab in relapsed/refractory acute lymphoblastic leukemia","description":"Key Points•\tMultiple mechanisms of acquired CD19 mutations and splicing contribute to CD19 loss and relapse to blinatumomab.•\tIdentification of CD19 ex2part levels represents a new biomarker predictive of resistance or likely failure of blinatumomab","abstract":"Key Points•\tMultiple mechanisms of acquired CD19 mutations and splicing contribute to CD19 loss and relapse to blinatumomab.•\tIdentification of CD19 ex2part levels represents a new biomarker predictive of resistance or likely failure of blinatumomab","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-13T22:07:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004028","title":"Exome Sequencing of Spanish Patients with rare genetic diseases.","description":"Whole exome sequencing of Spanish patients suffering from a rare genetic disease.  The study was carried out in 2013 as a part of a public call from CNAG (Centro Nacional de Análisis Genómico), where data of eight spanish families were sent to analyse. The study concluded with three solved cases: two of aniridia and one syndromic RP.","abstract":"Whole exome sequencing of Spanish patients suffering from a rare genetic disease.  The study was carried out in 2013 as a part of a public call from CNAG (Centro Nacional de Análisis Genómico), where data of eight spanish families were sent to analyse. The study concluded with three solved cases: two of aniridia and one syndromic RP.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-14T10:45:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004029","title":"GPMP2","description":null,"abstract":"We performed Whole genome sequencing and RNA-Sequencing on enhancing and non-enhancing glioblastoma samples.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004030","title":"Single-cell analysis reveals fibroblast clusters linked to immunotherapy resistance in cancer","description":"A subset of Cancer-Associated Fibroblasts (CAF-S1) mediates immunosuppression in breast cancers (BC), but its heterogeneity and its impact on immunotherapy response remain unknown. Here, we identify 8 CAF-S1 clusters by analyzing more than 18000 single CAF-S1 fibroblasts from BC. We validate the 5 most abundant clusters by flow cytometry and in silico analyses in other cancer types, highlighting their relevance. Myofibroblasts from clusters 0 and 3, characterized by extra-cellular matrix proteins and TGF signaling respectively, are indicative of primary resistance to immunotherapies. Cluster 0 up-regulates PD-1 and CTLA-4 protein levels in regulatory T lymphocytes (Tregs), which in turn increases CAF-S1 cluster 3 cellular content. Thus, our study highlights a positive feedback loop between specific CAF-S1 clusters and Tregs and uncovers their role in immunotherapy resistance.","abstract":"A subset of Cancer-Associated Fibroblasts (CAF-S1) mediates immunosuppression in breast cancers (BC), but its heterogeneity and its impact on immunotherapy response remain unknown. Here, we identify 8 CAF-S1 clusters by analyzing more than 18000 single CAF-S1 fibroblasts from BC. We validate the 5 most abundant clusters by flow cytometry and in silico analyses in other cancer types, highlighting their relevance. Myofibroblasts from clusters 0 and 3, characterized by extra-cellular matrix proteins and TGF signaling respectively, are indicative of primary resistance to immunotherapies. Cluster 0 up-regulates PD-1 and CTLA-4 protein levels in regulatory T lymphocytes (Tregs), which in turn increases CAF-S1 cluster 3 cellular content. Thus, our study highlights a positive feedback loop between specific CAF-S1 clusters and Tregs and uncovers their role in immunotherapy resistance.","study_type":"Other","pubmed_ids":[32434947],"external_links":null,"is_released":true,"released_date":"2019-11-15T16:08:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004031","title":"RNA-seq data from iCAF (sorted) and myCAF cluster 0 (spread) CAF-S1 fibroblasts maintained in culture","description":"RNA-seq data from iCAF (sorted) and myCAF cluster 0 (spread) CAF-S1 fibroblasts maintained in culture","abstract":"RNA-seq data from iCAF (sorted) and myCAF cluster 0 (spread) CAF-S1 fibroblasts maintained in culture","study_type":"Other","pubmed_ids":[32434947],"external_links":null,"is_released":true,"released_date":"2019-11-15T16:13:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004032","title":"RNA-seq data from Non Small Cell Lung Cancer (NSCLC) samples","description":"RNA-seq data from Non Small Cell Lung Cancer (NSCLC) samples","abstract":"RNA-seq data from Non Small Cell Lung Cancer (NSCLC) samples","study_type":"Other","pubmed_ids":[32434947],"external_links":null,"is_released":true,"released_date":"2019-11-15T16:18:18+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004033","title":"UCSF Pediatric Bithalamic Glioma Genome Project","description":"Brain tumors are the most common solid tumors of childhood, and the genetic drivers and optimal therapeutic strategies for many of the different subtypes remain unknown.  We performed targeted next-generation sequencing of approximately 500 cancer-associated genes on a cohort of 13 pediatric bithalamic diffuse gliomas, a lethal brain tumor of childhood for which the genetic basis is largely unknown.  We identified that bithalamic diffuse gliomas harbor frequent mutations in the EGFR oncogene in the absence of accompanying gene amplification and only rare histone H3 mutation. These EGFR mutations were either small in-frame insertions within exon 20 (intracellular tyrosine kinase domain) or missense mutations within exon 7 (extracellular ligand-binding domain).  Accompanying alterations included frequent TP53 mutation, CDK6 amplification or CDKN2C mutation, and BCOR and BCORL1 mutation or deletion.","abstract":"Brain tumors are the most common solid tumors of childhood, and the genetic drivers and optimal therapeutic strategies for many of the different subtypes remain unknown.  We performed targeted next-generation sequencing of approximately 500 cancer-associated genes on a cohort of 13 pediatric bithalamic diffuse gliomas, a lethal brain tumor of childhood for which the genetic basis is largely unknown.  We identified that bithalamic diffuse gliomas harbor frequent mutations in the EGFR oncogene in the absence of accompanying gene amplification and only rare histone H3 mutation. These EGFR mutations were either small in-frame insertions within exon 20 (intracellular tyrosine kinase domain) or missense mutations within exon 7 (extracellular ligand-binding domain).  Accompanying alterations included frequent TP53 mutation, CDK6 amplification or CDKN2C mutation, and BCOR and BCORL1 mutation or deletion.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-17T07:20:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004034","title":"GRIDSS, PURPLE, LINX: Unscrambling the tumor genome via integrated analysis of structural variation and copy number","description":"We have developed a novel, integrated and comprehensive purity, ploidy, structural variant and copy number somatic analysis toolkit for whole genome sequencing data of paired tumor/normal samples. We show that the combination of using GRIDSS for somatic structural variant calling and PURPLE for somatic copy number alteration calling allows highly sensitive, precise and consistent copy number and structural variant determination, as well as providing novel insights for short structural variants and regions of complex local topology. LINX, an interpretation tool, leverages the integrated structural variant and copy number calling to cluster individual structural variants into higher order events and chains them together to predict local derivative chromosome structure. LINX classifies and extensively annotates genomic rearrangements including simple and reciprocal breaks, LINE, viral and pseudogene insertions, and complex events such as chromothripsis. LINX also comprehensively calls genic fusions including chained fusions. Finally, our toolkit provides novel visualisation methods providing insight into complex genomic rearrangements.","abstract":"We have developed a novel, integrated and comprehensive purity, ploidy, structural variant and copy number somatic analysis toolkit for whole genome sequencing data of paired tumor/normal samples. We show that the combination of using GRIDSS for somatic structural variant calling and PURPLE for somatic copy number alteration calling allows highly sensitive, precise and consistent copy number and structural variant determination, as well as providing novel insights for short structural variants and regions of complex local topology. LINX, an interpretation tool, leverages the integrated structural variant and copy number calling to cluster individual structural variants into higher order events and chains them together to predict local derivative chromosome structure. LINX classifies and extensively annotates genomic rearrangements including simple and reciprocal breaks, LINE, viral and pseudogene insertions, and complex events such as chromothripsis. LINX also comprehensively calls genic fusions including chained fusions. Finally, our toolkit provides novel visualisation methods providing insight into complex genomic rearrangements.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-18T15:05:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004035","title":"Single Cell Sperm sequencing try 2","description":"Sequence single cell sperm using a 10X Chromium.  As a pilot test, we used samples from men who have had children with autism and normal controls.","abstract":"Sequence single cell sperm using a 10X Chromium.  As a pilot test, we used samples from men who have had children with autism and normal controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-18T15:08:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004036","title":"Genomic insight into the origins and dispersal of the Brazilian Coastal Natives","description":null,"abstract":"In the 15th century, approximately 900,000 Native Americans, mostly Tupí-speakers, lived on the Brazilian coast. By the end of the 18th century, the coastal native populations were declared extinct. The Tupí arrived on the east coast after leaving the Amazonian basin approximately 2,000 years before present; however, there is no consensus on how this migration occurred - toward the northern Amazon and then directly to the Atlantic coast, or heading south into the continent, and then migrating to the coast. Here we leveraged genomic data from one of the last remaining putative representatives of the Tupí coastal branch, a small, admixed, self-reported Tupiniquim community, as well as data of a Guaraní Mbyá native population from Southern Brazil and of three other native populations from the Amazonian region. We demonstrated that the Tupiniquim Native American ancestry is not related to any extant Brazilian Native American population already studied and thus they could be considered the only living representatives of the extinct Tupí branch that used to settle the Atlantic Coast of Brazil. Furthermore, these data show evidence of a direct migration from Amazon to the Northeast Coast in pre-Columbian time, giving rise to the Tupí Coastal populations, and a single distinct migration southward that originated the Guaraní people from Brazil and Paraguay. This is the first study to elucidate the population dynamics and diversification of the Brazilian Natives at a genomic level, which was made possible by recovering data from the Brazilian coastal population through the genomes of mestizo individuals.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-18T15:11:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004037","title":"Unravelling_sepsis_heterogeneity_through_trascriptomics__BioAID_Imperial","description":"There is marked heterogeneity in the septic response, which has hindered efforts to understand pathophysiology and develop targeted therapies. Molecular approaches may provide insights into variation in the host response, enabling biomarker development. Recent evidence suggests that transcriptomic sepsis response signatures (SRSs) can define patient subgroups associated with early outcome in sepsis. In this context, using transcriptomic approaches, the co-applicants were the first to identify differential gene signatures, or immune endotypes, correlating with outcome in sepsis, (Davenport E. et al, The Lancet Respiratory medicine, 2016); potentially providing a path to personalised treatment in sepsis. Specifically, this work defined two groups based on transcriptomic profiles: SRS group 1 being more associated with endotoxin tolerance demonstrating an immunosuppressed signature and is associated with higher mortality, whereas, SRS2 is more immune-heightened. However, despite the importance of these findings, previous studies have been underpowered, and limited in depth of data, to resolve these endophenotypes further. In this context, the Bioresource for Adult Infectious Disease (BioAID) offers substantial opportunities in terms of power, depth and breadth of data linked to biological samples of patients presenting acutely with the sepsis syndrome across the UK.  BioAID currently holds samples for DNA, RNA, serum and microbial isolates for more than 4,000 individuals (with a planned recruit of 10,000 individuals) and therefore provides a powerful resource for examining the underlying biology and correlates of sepsis syndrome with a view to informing early risk stratification of patients, need for critical care, and treatments.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"There is marked heterogeneity in the septic response, which has hindered efforts to understand pathophysiology and develop targeted therapies. Molecular approaches may provide insights into variation in the host response, enabling biomarker development. Recent evidence suggests that transcriptomic sepsis response signatures (SRSs) can define patient subgroups associated with early outcome in sepsis. In this context, using transcriptomic approaches, the co-applicants were the first to identify differential gene signatures, or immune endotypes, correlating with outcome in sepsis, (Davenport E. et al, The Lancet Respiratory medicine, 2016); potentially providing a path to personalised treatment in sepsis. Specifically, this work defined two groups based on transcriptomic profiles: SRS group 1 being more associated with endotoxin tolerance demonstrating an immunosuppressed signature and is associated with higher mortality, whereas, SRS2 is more immune-heightened. However, despite the importance of these findings, previous studies have been underpowered, and limited in depth of data, to resolve these endophenotypes further. In this context, the Bioresource for Adult Infectious Disease (BioAID) offers substantial opportunities in terms of power, depth and breadth of data linked to biological samples of patients presenting acutely with the sepsis syndrome across the UK.  BioAID currently holds samples for DNA, RNA, serum and microbial isolates for more than 4,000 individuals (with a planned recruit of 10,000 individuals) and therefore provides a powerful resource for examining the underlying biology and correlates of sepsis syndrome with a view to informing early risk stratification of patients, need for critical care, and treatments.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001004038","title":"Familial multinodular goitre and schwannomatosis","description":"Whole exome sequencing of a kindred with early-onset MNG and schwannomatosis with a germline pathogenic variants in DGCR8. MiRNA profiles of four tissue types were compared, and sequencing of MiRNA, pre-miRNA and mRNA was performed in a subset of 9 schwannomas, four of which harbor DGCR8-E518K.The variant identified is a somatic hotspot in WT and has been identified in two PTCs. Copy number loss of chromosome 22q, leading to loss of heterozygosity at the c.1552G&gt;A;p.E518K locus, was found in all 13 samples harboring c.1552G&gt;A;p.E518K. miRNA profiling of PTC, MNG, schwannomas and WT revealed a common profile among E518K hemizygous tumors.","abstract":"Whole exome sequencing of a kindred with early-onset MNG and schwannomatosis with a germline pathogenic variants in DGCR8. MiRNA profiles of four tissue types were compared, and sequencing of MiRNA, pre-miRNA and mRNA was performed in a subset of 9 schwannomas, four of which harbor DGCR8-E518K.The variant identified is a somatic hotspot in WT and has been identified in two PTCs. Copy number loss of chromosome 22q, leading to loss of heterozygosity at the c.1552G&gt;A;p.E518K locus, was found in all 13 samples harboring c.1552G&gt;A;p.E518K. miRNA profiling of PTC, MNG, schwannomas and WT revealed a common profile among E518K hemizygous tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004039","title":"Whole exome sequencing of 8 pairs of primary NSCLCs and distant metastases","description":null,"abstract":"This study is to understand of the molecular mechanisms driving metastasis.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004040","title":"HCA_Female_Reproductive_Adult_MRC_RNA","description":"Sexual reproduction depends on the fusion of haploid gametes during fertilisation to form a diploid embryo, and on the endocrine regulation of the endometrium by the ovary to provide conditions for successful implantation. In the present work, we will study the cell types and states, their spatial location and cellular interactions during the adult monthly remodelling of the endometrium. We will combine single-cell methods to create a molecular atlas of the female reproductive tissue in the adult life. \nThe work proposed here will hugely advance our understanding of the basic biology of human female reproduction. It will also give foundation to a better understanding of the causes of female infertility.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Sexual reproduction depends on the fusion of haploid gametes during fertilisation to form a diploid embryo, and on the endocrine regulation of the endometrium by the ovary to provide conditions for successful implantation. In the present work, we will study the cell types and states, their spatial location and cellular interactions during the adult monthly remodelling of the endometrium. We will combine single-cell methods to create a molecular atlas of the female reproductive tissue in the adult life. \nThe work proposed here will hugely advance our understanding of the basic biology of human female reproduction. It will also give foundation to a better understanding of the causes of female infertility.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004041","title":"Sequencing_of_Multiplexed_gRNA_Library","description":"This study will deep sequence 18 CRISPR screens performed in CGaP, aimed to characterise the impact of genetic variability on gene essentiality. Cas9+ iPS cells from healthy individuals were screened for survival using a minimised genome-wide library. Cell pellets were harvested at three time points when cells required passaging. Since the minimised library has two gRNA expression cassettes (aka 5' and 3' cassette), the study will generate two libraries per sample.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Gene knock-out phenotypes are known to vary across yeast strains and cancer cell lines. Human genes do not function the same way in different individuals. The extent to which gene essentiality and other cellular traits change between human individuals and the genetic determinants that suppress or enhance the deleterious effects of a mutation remain unknown. Here, we propose to measure the variation of human gene essentiality across different healthy donors using genome-wide CRISPR/Cas9 screens. We generated multiple Cas9-expressing monoclonal lines with high Cas9 activity for more than 40 induced pluripotent stem cell (iPSC) lines derived from different individuals. We have performed duplicate genome-wide dropout screens in these lines. CRISPR libraries were made from the CRISPR screens cell pellets and deep sequenced with illumina sequencing. The contributions of donor genotype, clonality of isogenic iPSC lines, experimental noise and other determinants to variation in gene essentiality will be validated and quantified. We expect variability in gene essentiality scores across different donors and this work will improve our understanding of how each gene impacts cellular growth and survival, and of gene essentiality in different genetic backgrounds.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004042","title":"Human Pancreatic Islet RNAseq - Lund","description":"Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, many key tissues and cell-types required for appropriate functional inference are absent from large-scale resources such as ENCODE and GTEx. We explored the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using RNA-Seq and genotyping data from 420 islet donors. We find: (a) eQTLs have a variable replication rate across the 44 GTEx  tissues (&lt;73%), indicating that our study captured islet-specific cis-eQTL signals; (b) islet eQTL signals show marked overlap with islet epigenome annotation, though eQTL effect size is reduced in the stretch enhancers most strongly implicated in GWAS signal location; (c) selective enrichment of islet eQTL overlap with the subset of T2D variants implicated in islet dysfunction; and (d) colocalization between islet eQTLs and variants influencing T2D or related glycemic traits, delivering candidate effector transcripts at 23 loci, including DGKB and TCF7L2.  Our findings illustrate the advantages of performing functional and regulatory studies in tissues of greatest disease-relevance while expanding our mechanistic insights into complex traits association loci activity with an expanded list of putative transcripts implicated in T2D development.","abstract":"Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, many key tissues and cell-types required for appropriate functional inference are absent from large-scale resources such as ENCODE and GTEx. We explored the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using RNA-Seq and genotyping data from 420 islet donors. We find: (a) eQTLs have a variable replication rate across the 44 GTEx  tissues (&lt;73%), indicating that our study captured islet-specific cis-eQTL signals; (b) islet eQTL signals show marked overlap with islet epigenome annotation, though eQTL effect size is reduced in the stretch enhancers most strongly implicated in GWAS signal location; (c) selective enrichment of islet eQTL overlap with the subset of T2D variants implicated in islet dysfunction; and (d) colocalization between islet eQTLs and variants influencing T2D or related glycemic traits, delivering candidate effector transcripts at 23 loci, including DGKB and TCF7L2.  Our findings illustrate the advantages of performing functional and regulatory studies in tissues of greatest disease-relevance while expanding our mechanistic insights into complex traits association loci activity with an expanded list of putative transcripts implicated in T2D development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-19T18:27:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004043","title":"Immune-awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy","description":"BACKGROUND: Our understanding of T cell evolution under checkpoint inhibitors (CPI) is still incomplete, restraining the achievement of full benefit from CPI.OBJECTIVES: We studied peripheral T cell turnover and evolution and their prognostic value after 3weeks on treatment with CPI (one cycle) analysing T cell receptor-β (TCR) sequences in plasma cell-free DNA (cfDNA) and PBMC, and performing a phenotypic analysis of peripheral T cell subsets.RESULTS: Peripheral T cell turnover and TCR repertoire dynamics correlated with response. Additionally, the cfDNA TCR repertoire reorganisation fingerprint correlated with the expansion of an immune-effector subset of peripheral T cells that predicted treatment response and identified the patients with longer overall survival.CONCLUSIONS: Here we show that prognostic changes in peripheral T cells occur within 3 weeks of commencing CPI treatment. This dynamic immune-awakening informs on the immune-system reorganization can be monitored using minimally invasive liquid biopsies.","abstract":"BACKGROUND: Our understanding of T cell evolution under checkpoint inhibitors (CPI) is still incomplete, restraining the achievement of full benefit from CPI.OBJECTIVES: We studied peripheral T cell turnover and evolution and their prognostic value after 3weeks on treatment with CPI (one cycle) analysing T cell receptor-β (TCR) sequences in plasma cell-free DNA (cfDNA) and PBMC, and performing a phenotypic analysis of peripheral T cell subsets.RESULTS: Peripheral T cell turnover and TCR repertoire dynamics correlated with response. Additionally, the cfDNA TCR repertoire reorganisation fingerprint correlated with the expansion of an immune-effector subset of peripheral T cells that predicted treatment response and identified the patients with longer overall survival.CONCLUSIONS: Here we show that prognostic changes in peripheral T cells occur within 3 weeks of commencing CPI treatment. This dynamic immune-awakening informs on the immune-system reorganization can be monitored using minimally invasive liquid biopsies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-20T12:25:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004044","title":"GWAS data on human pancreatic islets from 191 donors - Lund","description":"Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, many key tissues and cell-types required for appropriate functional inference are absent from large-scale resources such as ENCODE and GTEx. We explored the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using RNA-Seq and genotyping data from 420 islet donors. We find: (a) eQTLs have a variable replication rate across the 44 GTEx  tissues (&lt;73%), indicating that our study captured islet-specific cis-eQTL signals; (b) islet eQTL signals show marked overlap with islet epigenome annotation, though eQTL effect size is reduced in the stretch enhancers most strongly implicated in GWAS signal location; (c) selective enrichment of islet eQTL overlap with the subset of T2D variants implicated in islet dysfunction; and (d) colocalization between islet eQTLs and variants influencing T2D or related glycemic traits, delivering candidate effector transcripts at 23 loci, including DGKB and TCF7L2.  Our findings illustrate the advantages of performing functional and regulatory studies in tissues of greatest disease-relevance while expanding our mechanistic insights into complex traits association loci activity with an expanded list of putative transcripts implicated in T2D development.","abstract":"Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, many key tissues and cell-types required for appropriate functional inference are absent from large-scale resources such as ENCODE and GTEx. We explored the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using RNA-Seq and genotyping data from 420 islet donors. We find: (a) eQTLs have a variable replication rate across the 44 GTEx  tissues (&lt;73%), indicating that our study captured islet-specific cis-eQTL signals; (b) islet eQTL signals show marked overlap with islet epigenome annotation, though eQTL effect size is reduced in the stretch enhancers most strongly implicated in GWAS signal location; (c) selective enrichment of islet eQTL overlap with the subset of T2D variants implicated in islet dysfunction; and (d) colocalization between islet eQTLs and variants influencing T2D or related glycemic traits, delivering candidate effector transcripts at 23 loci, including DGKB and TCF7L2.  Our findings illustrate the advantages of performing functional and regulatory studies in tissues of greatest disease-relevance while expanding our mechanistic insights into complex traits association loci activity with an expanded list of putative transcripts implicated in T2D development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-20T18:41:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004045","title":"Whole exome sequencing (WES) and whole transcriptome sequencing (WTS) of a longitudinal breast cancer (BC) cohort consisting of 146 cases","description":"The molecular bases underlying neoadjuvant chemotherapy (NAC) response are poorly understood. To elucidate the effects of NAC on breast tumor biology and its association with clinical outcome, we have conducted whole exome sequencing (WES) of a longitudinal breast cancer (BC) cohort consisting of 146 cases (281 tumors, 109 pairs), including 52 (38%) that achieved pathologic complete responses (pCR) and 85 (62%) that harbored residual diseases at time of surgery.","abstract":"The molecular bases underlying neoadjuvant chemotherapy (NAC) response are poorly understood. To elucidate the effects of NAC on breast tumor biology and its association with clinical outcome, we have conducted whole exome sequencing (WES) of a longitudinal breast cancer (BC) cohort consisting of 146 cases (281 tumors, 109 pairs), including 52 (38%) that achieved pathologic complete responses (pCR) and 85 (62%) that harbored residual diseases at time of surgery.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004046","title":"MariaJasin_MCF10A_RAD51paralog_BRCA2_mutagenesis","description":"In collaboration with Maria Jasin at MSKCC, we are investigating the mutational signatures incurred as a result of BRCA2/RAD51B abrogation in breast epithelial primary cell MCF10A","abstract":"We have generated:\nBRCA2:\nBRCA2 knockouts  in MCF10A cells are inviable, however…  \nBRCA2 p53 cells are viable, although slow growing. \nBRCA2 knockout + S3291E mutant is viable without p53 mutation: these cells are proficient in HR, but defective in replication fork protection, so they provides an important model to specifically look at this function.\n\nRAD51B\nRAD51B knockouts unlike otherRAD51 paralogs are viable. They shows ~2-fold defect in HR and is sensitive to olaparib. \n\nWe plan to whole-genome sequence these cell lines for signature analysis, also with DNA damage if feasible.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004047","title":"Bottleneck_Sequencing_of_Human_Tissue__WGS_","description":"The study will explore genetic changes (somatic mutations) that occur throughout life in human joints and in degenerative joint diseases. The data in this study will be generated by whole-genome sequencing of laser-dissected microbiopsies and bulk blood samples from the synovium of patients with a range of degenerative joint diseases.","abstract":"The study will explore genetic changes (somatic mutations) that occur throughout life in human joints and in degenerative joint diseases. The data in this study will be generated by whole-genome sequencing of laser-dissected microbiopsies and bulk blood samples from the synovium of patients with a range of degenerative joint diseases.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004048","title":"Somatic_mutation_and_clonal_evolution_in_the_human_testes___Targeted","description":"n this study we aim to characterise the landscape of Pathogenic variants and clonal dynamics in normal and cancerous testes and their role in cancer predisposition. The study combines targeted sequencing and whole-genome sequencing of microbiopsies from testes. The range of patients studied will include healthy individuals, and patients with testicular cancer.","abstract":"In this study we aim to determine the clonal dynamics of spermatogenesis in adult testes and identify factors such as age that affect clonal dynamics.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004049","title":"Test Study","description":null,"abstract":"This is a sample study for EGA testing.\nSample study. \nSample Study","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004050","title":"Neoantigen responses to Immunotherapy in Prostate Cancer","description":"To determine whether antigen-specific T cell responses can be elicited following treatment with ICT in cancers that have a low TMB, a clinical trial with ipilimumab (anti-CTLA-4) was conducted in 30 patients with metastatic castration-resistant prostate cancer (CRPC). We identified 2 distinct groups of patients divided by clinical outcomes, which consisted of a cohort with Favorable and Unfavorable outcomes. Compared to the Unfavorable cohort, the patients in the Favorable cohort were more likely to have higher intratumoral CD8 T cell density and/or IFN-γ response gene signature, including five patients who had antigen-specific T cell responses that were only detectable after ipilimumab therapy. Three patients had T cell responses against tumor-associated antigens (PSMA and PAP). Importantly, two patients with a relatively low TMB had T cell responses against unique neoantigens. Collectively, our data indicate that a subset of patients with metastatic prostate cancer benefit from ICTs, particularly those who have immunological biomarkers associated with effector T cell responses.\n\nPublication:\n\nSumit K. Subudhi, Luis Vence, Hao Zhao, Jorge Blando, Shalini S. Yadav, Qing Xiong, Alexandre Reuben, Ana Aparicio, Paul G. Corn, Brian F. Chapin, Louis L. Pisters, Patricia Troncoso, Rebecca Slack Tidwell, Peter Thall, Chang-Jiun Wu, Jianhua Zhang, Christopher L. Logothetis, Andrew Futreal, James P. Allison and Padmanee Sharma, 2020, Neoantigen responses, immune correlates, and favorable outcomes after ipilimumab treatment of patients with prostate cancer. Science Translational Medicine, 01 Apr 2020:Vol. 12, Issue 537, eaaz3577DOI: 10.1126/scitranslmed.aaz3577. https://pubmed.ncbi.nlm.nih.gov/32238575/","abstract":"To determine whether antigen-specific T cell responses can be elicited following treatment with ICT in cancers that have a low TMB, a clinical trial with ipilimumab (anti-CTLA-4) was conducted in 30 patients with metastatic castration-resistant prostate cancer (CRPC). We identified 2 distinct groups of patients divided by clinical outcomes, which consisted of a cohort with Favorable and Unfavorable outcomes. Compared to the Unfavorable cohort, the patients in the Favorable cohort were more likely to have higher intratumoral CD8 T cell density and/or IFN-γ response gene signature, including five patients who had antigen-specific T cell responses that were only detectable after ipilimumab therapy. Three patients had T cell responses against tumor-associated antigens (PSMA and PAP). Importantly, two patients with a relatively low TMB had T cell responses against unique neoantigens. Collectively, our data indicate that a subset of patients with metastatic prostate cancer benefit from ICTs, particularly those who have immunological biomarkers associated with effector T cell responses.\n\nPublication:\n\nSumit K. Subudhi, Luis Vence, Hao Zhao, Jorge Blando, Shalini S. Yadav, Qing Xiong, Alexandre Reuben, Ana Aparicio, Paul G. Corn, Brian F. Chapin, Louis L. Pisters, Patricia Troncoso, Rebecca Slack Tidwell, Peter Thall, Chang-Jiun Wu, Jianhua Zhang, Christopher L. Logothetis, Andrew Futreal, James P. Allison and Padmanee Sharma, 2020, Neoantigen responses, immune correlates, and favorable outcomes after ipilimumab treatment of patients with prostate cancer. Science Translational Medicine, 01 Apr 2020:Vol. 12, Issue 537, eaaz3577DOI: 10.1126/scitranslmed.aaz3577. https://pubmed.ncbi.nlm.nih.gov/32238575/","study_type":"Other","pubmed_ids":[32238575],"external_links":null,"is_released":true,"released_date":"2019-11-21T16:33:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004051","title":"Oesophageal_Adenocarcinoma_Organoids_Iso_Seq","description":"RNA Sequencing of 5 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical rescetion of the tumour. All model derivations took place with the CGaP facility in Sanger.  This PacBio RNA data will be combined with other sequencing data in order to generate accurate reference cancer genomes and study how structural variants affect gene expression","abstract":"There is complex interplay between underlying genetic sequence and epigenetic factors, however this interplay is still illusive. Massively reconstructed cancer genomes can be used in order to better understand this relationship. Six oesophageal adenocarcinoma organoids will be sequenced using long read sequencing technologies and will be profiled for a range of epigenetic marks. Combination of genetic and epigenetic data will allow the thorough characterisation of reference cancer genomes and will provide novel insights into mechanisms of gene regulation.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-21T17:13:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004052","title":"Homo sapiens study for testing","description":null,"abstract":"its a sample study to check the EGA functionality from metabolights","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004053","title":"Cell type-specific transcriptomics of esophageal adenocarcinoma as a scalable alternative for single cell transcriptomics","description":"We developed a protocol for the separation of esophageal carcinoma tissue into leukocytes (using CD45 as a marker), epithelial cells (EpCAM), and fibroblasts (two out of PDGFRA, CD90, anti-fibroblast) by fluorescence-activated cell sorting followed by RNA-sequencing","abstract":"We developed a protocol for the separation of esophageal carcinoma tissue into leukocytes (using CD45 as a marker), epithelial cells (EpCAM), and fibroblasts (two out of PDGFRA, CD90, anti-fibroblast) by fluorescence-activated cell sorting followed by RNA-sequencing","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-22T14:20:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004054","title":"Repeat UVA exposure of human skin fibroblasts induces both a transitionary and recovery methylation response","description":null,"abstract":"Ultraviolet A (UVA) radiation drives skin photoaging in the dermis, plausibly via persistent changes to DNA methylation in dermal fibroblasts. We assessed genome-wide DNA methylation changes after 5 repeat daily UVA doses at 48 hours (transitionary) and 1-week (recovery) post-final irradiation. Data analysis revealed that UVA irradiation induced distinct transitionary and recovery-associated DNA methylation responses in fibroblasts with contrasting functional characteristics.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004055","title":"Concurrent germline and somatic pathogenic BAP1 variants in a patient with metastatic bladder cancer","description":null,"abstract":"Germline pathogenic variants in the BRCA1-associated protein-1 (BAP1) gene cause the BAP1-tumor predisposition syndrome (BAP1-TPDS). BAP1-TPDS is associated with an increased risk of uveal and cutaneous melanoma, mesothelioma, renal cell carcinoma, and several other cancer subtypes. Here, we report a novel germline nonsense BAP1 variant (c.850G&gt;T, p.Glu284Ter) in a patient with bladder cancer and a strong family history of malignancy. A concurrently identified somatic frameshift BAP1 variant and the predicted deleterious effects of the germline BAP1 variant provide strong evidence of pathogenicity in this case. With the addition of bladder cancer to the tumor types reported with germline BAP1 mutations, our understanding of BAP1-TPDS continues to evolve and may affect future screening and surveillance guidelines.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-25T17:49:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004056","title":"Phenotyping data on human pancreatic islets from 191 donors - Lund","description":"Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, many key tissues and cell-types required for appropriate functional inference are absent from large-scale resources such as ENCODE and GTEx. We explored the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using RNA-Seq and genotyping data from 420 islet donors. We find: (a) eQTLs have a variable replication rate across the 44 GTEx  tissues (&amp;lt;73%), indicating that our study captured islet-specific cis-eQTL signals; (b) islet eQTL signals show marked overlap with islet epigenome annotation, though eQTL effect size is reduced in the stretch enhancers most strongly implicated in GWAS signal location; (c) selective enrichment of islet eQTL overlap with the subset of T2D variants implicated in islet dysfunction; and (d) colocalization between islet eQTLs and variants influencing T2D or related glycemic traits, delivering candidate effector transcripts at 23 loci, including DGKB and TCF7L2.  Our findings illustrate the advantages of performing functional and regulatory studies in tissues of greatest disease-relevance while expanding our mechanistic insights into complex traits association loci activity with an expanded list of putative transcripts implicated in T2D development.","abstract":"Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, many key tissues and cell-types required for appropriate functional inference are absent from large-scale resources such as ENCODE and GTEx. We explored the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using RNA-Seq and genotyping data from 420 islet donors. We find: (a) eQTLs have a variable replication rate across the 44 GTEx  tissues (&amp;lt;73%), indicating that our study captured islet-specific cis-eQTL signals; (b) islet eQTL signals show marked overlap with islet epigenome annotation, though eQTL effect size is reduced in the stretch enhancers most strongly implicated in GWAS signal location; (c) selective enrichment of islet eQTL overlap with the subset of T2D variants implicated in islet dysfunction; and (d) colocalization between islet eQTLs and variants influencing T2D or related glycemic traits, delivering candidate effector transcripts at 23 loci, including DGKB and TCF7L2.  Our findings illustrate the advantages of performing functional and regulatory studies in tissues of greatest disease-relevance while expanding our mechanistic insights into complex traits association loci activity with an expanded list of putative transcripts implicated in T2D development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-25T19:57:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004057","title":"Molecular Attributes Underlying Central Nervous System and Systemic Relapse in Diffuse Large B-cell Lymphoma","description":"Central nervous system (CNS) relapse in diffuse large B-cell lymphoma remains a significant conundrum. While clinical risk scores and biomarkers allow the identification of patients with higher risk of CNS relapse, their predictive ability is low. Herein, we report findings from a comprehensive study examining gene expression changes, mutations and clonal evolution. Firstly, considering diagnostic samples from patients with CNS relapse, systemic relapse or no relapse, we found a striking enrichment of gene expression changes reflecting protein biosynthesis in patients who experienced CNS or systemic relapse. Furthermore, diagnostic specimens of relapsing cases were characterized by low immune infiltrates. The most discriminative gene feature in our analysis was SLAMF1, high expression of which was associated with favourable outcomes. Next, we assessed whether specific gene mutations were associated with subsequent CNS or systemic relapse. Activated B-cell-like genes such as PIM1, CD79B and PRDM1 were more frequently mutated in cases with CNS relapse, whereas TP53, BCL2 and FOXO1 mutations were associated with systemic relapse. Lastly, we performed tumor evolution analysis in five patients, identifying significant clonal divergence that accompanied CNS relapse. In summary, we identified both common biology underlying both CNS and systemic relapse, independent of cell-of-origin (COO), and specific COO-enriched gene mutations that conferred a higher risk of either CNS or systemic relapse. Moreover, we identified a pattern of clonal evolution that can explain difficulties in both predicting and treating CNS relapse.","abstract":"Central nervous system (CNS) relapse in diffuse large B-cell lymphoma remains a significant conundrum. While clinical risk scores and biomarkers allow the identification of patients with higher risk of CNS relapse, their predictive ability is low. Herein, we report findings from a comprehensive study examining gene expression changes, mutations and clonal evolution. Firstly, considering diagnostic samples from patients with CNS relapse, systemic relapse or no relapse, we found a striking enrichment of gene expression changes reflecting protein biosynthesis in patients who experienced CNS or systemic relapse. Furthermore, diagnostic specimens of relapsing cases were characterized by low immune infiltrates. The most discriminative gene feature in our analysis was SLAMF1, high expression of which was associated with favourable outcomes. Next, we assessed whether specific gene mutations were associated with subsequent CNS or systemic relapse. Activated B-cell-like genes such as PIM1, CD79B and PRDM1 were more frequently mutated in cases with CNS relapse, whereas TP53, BCL2 and FOXO1 mutations were associated with systemic relapse. Lastly, we performed tumor evolution analysis in five patients, identifying significant clonal divergence that accompanied CNS relapse. In summary, we identified both common biology underlying both CNS and systemic relapse, independent of cell-of-origin (COO), and specific COO-enriched gene mutations that conferred a higher risk of either CNS or systemic relapse. Moreover, we identified a pattern of clonal evolution that can explain difficulties in both predicting and treating CNS relapse.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-25T20:34:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004058","title":"HCA_Kidney_Adult_MRC_RNA","description":"Defining regional anatomical variation in cellular composition, transcriptome and epigenome in the human kidney \nThe kidneys play a critical role in homeostasis, excreting waste and acid and maintaining electrolyte and water balance. The homeostatic function of the kidney generates substantial differences in tissue environment between different anatomical regions of the kidney. Complementing efforts in generating single-cell molecular profiles across the entire cross-section of the adult human kidney, from outer cortex to upper ureter, we aim to also interrogate whether the epigenome of kidney-resident immune cells varies across different anatomical regions of the kidney. The expression of RNA transcripts is, in part, controlled by the state of chromatin, with closed structures sterically hindering the binding of transcriptional modulators. The chromatin landscape of immune cells can change according to environmental stimuli, for example, via engagement of toll-like receptor (TLR)4 with lipopolysaccharide. Here we wish to determine whether and how the environmental differences in cortex, medulla and pelvis might impact resident immune cell epigenome using single-cell ATAC-seq on the 10x platform.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Defining regional anatomical variation in cellular composition, transcriptome and epigenome in the human kidney \nThe kidneys play a critical role in homeostasis, excreting waste and acid and maintaining electrolyte and water balance. The homeostatic function of the kidney generates substantial differences in tissue environment between different anatomical regions of the kidney. Complementing efforts in generating single-cell molecular profiles across the entire cross-section of the adult human kidney, from outer cortex to upper ureter, we aim to also interrogate whether the epigenome of kidney-resident immune cells varies across different anatomical regions of the kidney. The expression of RNA transcripts is, in part, controlled by the state of chromatin, with closed structures sterically hindering the binding of transcriptional modulators. The chromatin landscape of immune cells can change according to environmental stimuli, for example, via engagement of toll-like receptor (TLR)4 with lipopolysaccharide. Here we wish to determine whether and how the environmental differences in cortex, medulla and pelvis might impact resident immune cell epigenome using single-cell ATAC-seq on the 10x platform.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004059","title":"Expression profiles and genetic makeup of metastases of a cancer of unknown primary.","description":null,"abstract":"Aims: \n(i) to perform gene epression profiles; (ii) to decipher the genetic similarity (if present); (iii) to investigate the clonal dynamics and (iv) to infer the phylogenetic trajectories of multiple metastases within an individual CUP patient.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-26T14:57:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004060","title":"Effects_of_Chemotherapy_on_the_Somatic_Mutational_Landscape_in_Normal_Human_Tissue___WES","description":"his study is investigating the effects of chemotherapy drugs used in cancer treatment on the somatic mutational landscape in normal human tissues. The samples used in this study have been taken from rapid autopsies of patients who have undergone chemotherapy using drugs thought to cause mutations in the DNA. Structures from a variety of tissues will be dissected using LCM and whole genome sequences will be produced in order to assess mutational burdens and signatures.","abstract":"his study is investigating the effects of chemotherapy drugs used in cancer treatment on the somatic mutational landscape in normal human tissues. The samples used in this study have been taken from rapid autopsies of patients who have undergone chemotherapy using drugs thought to cause mutations in the DNA. Structures from a variety of tissues will be dissected using LCM and whole genome sequences will be produced in order to assess mutational burdens and signatures.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004061","title":"Effects_of_Chemotherapy_on_the_Somatic_Mutational_Landscape_in_Normal_Human_Tissue___WGS","description":"This study is investigating the effects of chemotherapy drugs used in cancer treatment on the somatic mutational landscape in normal human tissues. The samples used in this study have been taken from rapid autopsies of patients who have undergone chemotherapy using drugs thought to cause mutations in the DNA. Structures from a variety of tissues will be dissected using LCM and whole genome sequences will be produced in order to assess mutational burdens and signatures.","abstract":"This study is investigating the effects of chemotherapy drugs used in cancer treatment on the somatic mutational landscape in normal human tissues. The samples used in this study have been taken from rapid autopsies of patients who have undergone chemotherapy using drugs thought to cause mutations in the DNA. Structures from a variety of tissues will be dissected using LCM and whole genome sequences will be produced in order to assess mutational burdens and signatures.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004062","title":"Studydraft","description":null,"abstract":"wgs study because they didn't like the first attempt","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004063","title":"Organoid cultures of early-onset colorectal cancers reveal distinct and rare genetic profiles","description":"Sporadic early-onset colorectal cancer (EOCRC) has bad prognosis, yet is poorly represented by cell line models. We examine the key mutational and transcriptomic alterations in an organoid biobank enriched in EOCRCs. We established paired cancer (n=32) and normal organoids (n=18) from 20 patients enriched in microsatellite-stable EOCRC. Exome and transcriptome analysis was performed. We observed a striking diversity of molecular phenotypes, including PTPRK-RSPO3 fusions. Transcriptionally, RSPO fusion organoids resembled normal colon organoids and were distinct from APC mutant organoids, with high BMP2 and low PTK7 expression. Single cell transcriptome analysis confirmed the similarity between RSPO fusion organoids and normal organoids, with a propensity for maturation on Wnt withdrawal, whereas the APC mutant organoids were locked in progenitor stages. CRISPR/Cas9 engineered mutation of APC in normal human colon organoids led to upregulation of PTK7 protein and suppression of BMP2, but less so with an engineered RNF43 mutation. The frequent co-occurrence of RSPO fusions with SMAD4 or BMPR1A mutation was confirmed in TCGA database searches. RNF43 mutation was found in organoid from a leukaemia survivor with a novel mutational signature; and organoids with POLE proofreading mutation displayed ultramutation. The cancer organoid genomes were stable over long culture periods, while normal human colon organoids tended to be subject to clonal dominance over time. These organoid models enriched in EOCRCs with linked genomic data fill a gap in existing CRC models and reveal distinct genetic profiles and novel pathway cooperativity.","abstract":"Sporadic early-onset colorectal cancer (EOCRC) has bad prognosis, yet is poorly represented by cell line models. We examine the key mutational and transcriptomic alterations in an organoid biobank enriched in EOCRCs. We established paired cancer (n=32) and normal organoids (n=18) from 20 patients enriched in microsatellite-stable EOCRC. Exome and transcriptome analysis was performed. We observed a striking diversity of molecular phenotypes, including PTPRK-RSPO3 fusions. Transcriptionally, RSPO fusion organoids resembled normal colon organoids and were distinct from APC mutant organoids, with high BMP2 and low PTK7 expression. Single cell transcriptome analysis confirmed the similarity between RSPO fusion organoids and normal organoids, with a propensity for maturation on Wnt withdrawal, whereas the APC mutant organoids were locked in progenitor stages. CRISPR/Cas9 engineered mutation of APC in normal human colon organoids led to upregulation of PTK7 protein and suppression of BMP2, but less so with an engineered RNF43 mutation. The frequent co-occurrence of RSPO fusions with SMAD4 or BMPR1A mutation was confirmed in TCGA database searches. RNF43 mutation was found in organoid from a leukaemia survivor with a novel mutational signature; and organoids with POLE proofreading mutation displayed ultramutation. The cancer organoid genomes were stable over long culture periods, while normal human colon organoids tended to be subject to clonal dominance over time. These organoid models enriched in EOCRCs with linked genomic data fill a gap in existing CRC models and reveal distinct genetic profiles and novel pathway cooperativity.","study_type":"Other","pubmed_ids":[32217638],"external_links":null,"is_released":true,"released_date":"2019-11-27T06:14:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004064","title":"Heterogeneous metabolic signatures are linked to cancer cell differentiation in colorectal cancer","description":"Colorectal cancer (CRC) is characterized by functional intratumor heterogeneity that  shares many similarites with the hierarchical organization of the normal intestinal epithelium. In order to relate transcriptional subtypes to functional tumor cell heterogeneity we applied scRNA-seq to 12 patient-derived CRC spheroid cultures. We identified shared expression programs that relate to intestinal lineages and revealed metabolic signatures that are linked to cancer cell differentiation. In addition, we validated and complemented sequencing results by quantitative microscopy using live-dyes and multiplexed RNA fluorescence in situ hybridization, thereby revealing metabolic compartmentalization and potential cell-cell interactions. FInally, we demonstrate  functional differences between metabolically distinct lineage subtypes that might have strong implications for future treatment strategies of CRC.","abstract":"Colorectal cancer (CRC) is characterized by functional intratumor heterogeneity that  shares many similarites with the hierarchical organization of the normal intestinal epithelium. In order to relate transcriptional subtypes to functional tumor cell heterogeneity we applied scRNA-seq to 12 patient-derived CRC spheroid cultures. We identified shared expression programs that relate to intestinal lineages and revealed metabolic signatures that are linked to cancer cell differentiation. In addition, we validated and complemented sequencing results by quantitative microscopy using live-dyes and multiplexed RNA fluorescence in situ hybridization, thereby revealing metabolic compartmentalization and potential cell-cell interactions. FInally, we demonstrate  functional differences between metabolically distinct lineage subtypes that might have strong implications for future treatment strategies of CRC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-27T07:59:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004065","title":"27th November","description":null,"abstract":"27th November","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004066","title":"Bottleneck_Sequencing_Of_Human_Tissue__Wgs_","description":"Bottleneck sequencing of human tissue including neurons, cord blood, sperm\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Study somatic mutation in neurons, including mutation burden accumulation through lifespan, mutational signatures and comparison between healthy and Alzheimer patients. Brain samples from DNA repair defficient samples are also included. The plate also contains sperm, cord blood, and endometrium samples.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-27T14:49:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004067","title":"HCA_Gut_Adult_WSSS_RNA_Oxford","description":"Human Cell Atlas for gut - Adult RNA work. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Human Cell Atlas for gut - Adult RNA work. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004068","title":"HCA_Gut_disease_Coeliac_WSSS_RNA","description":"Human Cell Atlas for gut - Adult RNA work. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Human Cell Atlas for gut - Adult RNA work. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004069","title":"HCA_Placenta_Adult_Vento_RNA","description":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess human development. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs).\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess human development. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs).\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-11-27T16:28:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004070","title":"single-cell RNA-seq Case-Control study of children progressing to Type1 diabetes","description":"Single-cell RNA sequencing was carried out on four selected PBMC samples of  Finnish children at risk of developing Type 1 diabetes and their gender age and HLA matched control children using 10X genomic platform. All four Case children were positive for multiple islet specific autoantibodies and two of them also progressed to clinical disease during the follow up whereas the control children remain negative for all autoantibodies. Age at seroconversion for Case 2, 3, 5, and 9 children is 12, 18, 24, and 18 months, respectively. Age at sampling, in months, for the pairs was as follows (Case/Control): pair 2:24/24; pair 3: 12/18; pair 5: 12/12; pair 9:24/18.","abstract":"Single-cell RNA sequencing was carried out on four selected PBMC samples of  Finnish children at risk of developing Type 1 diabetes and their gender age and HLA matched control children using 10X genomic platform. All four Case children were positive for multiple islet specific autoantibodies and two of them also progressed to clinical disease during the follow up whereas the control children remain negative for all autoantibodies. Age at seroconversion for Case 2, 3, 5, and 9 children is 12, 18, 24, and 18 months, respectively. Age at sampling, in months, for the pairs was as follows (Case/Control): pair 2:24/24; pair 3: 12/18; pair 5: 12/12; pair 9:24/18.","study_type":"Other","pubmed_ids":[31311800],"external_links":null,"is_released":true,"released_date":"2019-11-29T09:35:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004071","title":"RNA-seq study of longitudinal blood cell samples from children at risk of type 1 diabetes","description":"The appearance of type 1 diabetes (T1D)-associated autoantibodies is the first and only measurable parameter to predict progression toward T1D in genetically susceptible individuals. However, autoantibodies indicate an active autoimmune reaction, wherein the immune tolerance is already broken. Therefore, there is a clear and urgent need for new biomarkers that predict the onset of the autoimmune reaction preceding auto-antibody positivity or reflect progressive b-cell destruction. Here we report the mRNA sequencing–based analysis of 306 samples including fractionated samples of CD4+ and CD8+ T cells as well as CD4, CD8 cell fractions and unfractionated PBMC samples longitudinally collected from seven children who developed beta-cell autoimmunity (Case subjects) at a young age and matched control subjects.","abstract":"The appearance of type 1 diabetes (T1D)-associated autoantibodies is the first and only measurable parameter to predict progression toward T1D in genetically susceptible individuals. However, autoantibodies indicate an active autoimmune reaction, wherein the immune tolerance is already broken. Therefore, there is a clear and urgent need for new biomarkers that predict the onset of the autoimmune reaction preceding auto-antibody positivity or reflect progressive b-cell destruction. Here we report the mRNA sequencing–based analysis of 306 samples including fractionated samples of CD4+ and CD8+ T cells as well as CD4, CD8 cell fractions and unfractionated PBMC samples longitudinally collected from seven children who developed beta-cell autoimmunity (Case subjects) at a young age and matched control subjects.","study_type":"Other","pubmed_ids":[31311800],"external_links":null,"is_released":true,"released_date":"2019-11-29T12:40:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004072","title":"29th November","description":null,"abstract":"29th November","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004073","title":"Test_Final_29","description":null,"abstract":"Test_Final_29","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004074","title":"Neoadjuvant combination PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable urothelial carcinoma","description":"Immune checkpoint therapy (ICT) is being tested in the neoadjuvant setting for patients with localized urothelial carcinoma (UC), with one study reporting data in cisplatin-ineligible patients who received anti PD-L1 monotherapy. The study reported that patients with bulky tumors, a known high-risk feature defined as greater than clinical T2 disease, had fewer responses, with pathologic complete response (pCR) rate of 17%. Here, we report on the first pilot combination neoadjuvant trial (NCT02812420) with anti-PD-L1 (durvalumab) plus anti-CTLA-4 (tremelimumab) in cisplatin-ineligible patients, with all tumors identified as having high risk features (N=28). Primary endpoint was safety and we observed 6 of 28 patients (21%) with\ngrade ≥3 immune-related adverse events, consisting of asymptomatic laboratory abnormalities (N=4), hepatitis and colitis (N=2). We also observed pCR of 37.5% and downstaging to pT1 or less in 58% of patients who completed surgery (N=24). In summary, we provide initial safety, efficacy and biomarker data with neoadjuvant combination anti-PD-L1 plus anti-CTLA-4, which warrants further development for patients with localized UC, especially cisplatin-ineligible patients with high-risk features who do not currently have an established standard-of-care neoadjuvant treatment.\n\nPublication:\n\nGao et al. Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma. Nature Medicine volume 26, pages1845–1851(2020)","abstract":"Immune checkpoint therapy (ICT) is being tested in the neoadjuvant setting for patients with localized urothelial carcinoma (UC), with one study reporting data in cisplatin-ineligible patients who received anti PD-L1 monotherapy. The study reported that patients with bulky tumors, a known high-risk feature defined as greater than clinical T2 disease, had fewer responses, with pathologic complete response (pCR) rate of 17%. Here, we report on the first pilot combination neoadjuvant trial (NCT02812420) with anti-PD-L1 (durvalumab) plus anti-CTLA-4 (tremelimumab) in cisplatin-ineligible patients, with all tumors identified as having high risk features (N=28). Primary endpoint was safety and we observed 6 of 28 patients (21%) with\ngrade ≥3 immune-related adverse events, consisting of asymptomatic laboratory abnormalities (N=4), hepatitis and colitis (N=2). We also observed pCR of 37.5% and downstaging to pT1 or less in 58% of patients who completed surgery (N=24). In summary, we provide initial safety, efficacy and biomarker data with neoadjuvant combination anti-PD-L1 plus anti-CTLA-4, which warrants further development for patients with localized UC, especially cisplatin-ineligible patients with high-risk features who do not currently have an established standard-of-care neoadjuvant treatment.\n\nPublication:\n\nGao et al. Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma. Nature Medicine volume 26, pages1845–1851(2020)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-02T17:50:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004075","title":"The Jerusalem Perinatal Study (JPS) aimed to examine the developmental origins of cardiometabolic risk.","description":"The Jerusalem Perinatal Study (JPS) aimed to examine the developmental origins of cardiometabolic risk and explore the mechanisms underlying the associations between perinatal characteristics and the development of risk for adult chronic disease. In other words, the cohort has enabled the examination of associations between maternal and paternal characteristics with cardiometabolic risk variables in offspring at various points in the life course, as well as the effect of longitudinal changes in characteristics in both parents and offspring.","abstract":"The Jerusalem Perinatal Study (JPS) aimed to examine the developmental origins of cardiometabolic risk and explore the mechanisms underlying the associations between perinatal characteristics and the development of risk for adult chronic disease. In other words, the cohort has enabled the examination of associations between maternal and paternal characteristics with cardiometabolic risk variables in offspring at various points in the life course, as well as the effect of longitudinal changes in characteristics in both parents and offspring.","study_type":"Other","pubmed_ids":[26163255,26451733,27417428,27651384,29106309,29273651,30605457],"external_links":null,"is_released":true,"released_date":"2019-12-03T15:21:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004076","title":"Molecular and Clonal Evolution in Recurrent Metastatic Gliosarcoma","description":"We present a rare case of a 37-year-old woman who was initially diagnosed with IDH wild-type gliosarcoma in the frontal lobe and later developed two local recurrences and extracranial metastases to the vertebral and pelvic bones. In order to understand the clonal relationships between the four tumor instances and the origin of metastasis, we performed whole genome sequencing of the intracranial tumors and the tumor located in the right iliac bone. Mutational and copy number profile comparisons of the metastatic to intracranial tumors highlighted a high similarity in molecular profile, but contrasting evidence regarding the origin of the metastasis. Subclonal reconstruction suggested a parallel evolution of the recurrent tumors, and that the metastatic tumor was largely derived from the first recurrence. We conclude that metastasis in glioma can be a late event in tumorigenesis.","abstract":"We present a rare case of a 37-year-old woman who was initially diagnosed with IDH wild-type gliosarcoma in the frontal lobe and later developed two local recurrences and extracranial metastases to the vertebral and pelvic bones. In order to understand the clonal relationships between the four tumor instances and the origin of metastasis, we performed whole genome sequencing of the intracranial tumors and the tumor located in the right iliac bone. Mutational and copy number profile comparisons of the metastatic to intracranial tumors highlighted a high similarity in molecular profile, but contrasting evidence regarding the origin of the metastasis. Subclonal reconstruction suggested a parallel evolution of the recurrent tumors, and that the metastatic tumor was largely derived from the first recurrence. We conclude that metastasis in glioma can be a late event in tumorigenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-03T16:45:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004077","title":"Whole exome sequencing study for 8 pairs of primary NSCLCs and distant metastases","description":"This study is to understand of the molecular mechanisms driving metastasis.","abstract":"This study is to understand of the molecular mechanisms driving metastasis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-03T17:05:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004078","title":"RNA sequencing study for 8 pairs of primary NSCLCs and distant metastases","description":"This study is to understand of the molecular mechanisms driving metastasis.","abstract":"This study is to understand of the molecular mechanisms driving metastasis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-03T17:05:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004079","title":"DNA methylation array study for 7 pairs of primary NSCLCs and distant metastases","description":"This study is to compare DNA methylation profiles between primary NSCLCs and paired distant metastases.","abstract":"This study is to compare DNA methylation profiles between primary NSCLCs and paired distant metastases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-03T20:13:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004080","title":"End structure of DNA in plasma: detection, characterizationand diagnostic applications","description":"The physical properties of cell-free DNA fragments in plasma, such as fragment sizes and ends, have attracted much recent interest, leading to the emerging field of fragmentomics. This study attempted to further characterize the end structure of plasma DNA.","abstract":"The physical properties of cell-free DNA fragments in plasma, such as fragment sizes and ends, have attracted much recent interest, leading to the emerging field of fragmentomics. This study attempted to further characterize the end structure of plasma DNA.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-04T02:01:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004081","title":"RNA sequencing of CD8 T cells from melanoma patients prior to and during checkpoint immunotherapy and untreated healthy controls","description":"We are interested in inter-individual variation in transcriptional response to immune checkpoint blockade. We have analysed poly A purified RNA expression from CD8 T cells (297 transcriptomes in total) isolated from metastatic melanoma patients (n=106) prior to and during treatment with either single agent (Pembrolizumab) or combination (Ipilimumab/ Nivolumab) immune checkpoint blockade. We compare expression at different stages of treatment and additionally contrast this with that from healthy controls (n=68).","abstract":"We are interested in inter-individual variation in transcriptional response to immune checkpoint blockade. We have analysed poly A purified RNA expression from CD8 T cells (297 transcriptomes in total) isolated from metastatic melanoma patients (n=106) prior to and during treatment with either single agent (Pembrolizumab) or combination (Ipilimumab/ Nivolumab) immune checkpoint blockade. We compare expression at different stages of treatment and additionally contrast this with that from healthy controls (n=68).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-04T08:21:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004082","title":"Single cell RNA-seq mapping of nasal and tracheobronchial airways in human healthy volunteers","description":"The respiratory tract constitutes an elaborated line of defense based on a unique cellular ecosystem. Single-cell profiling methods enable the investigation of cell population distributions and transcriptional changes along the airways. We have explored cellular heterogeneity of the human airway epithelium in 10 healthy living volunteers by single-cell RNA profiling. 77,969 cells were collected by bronchoscopy at 35 distinct locations, from the nose to the 12th division of the airway tree. The resulting atlas is composed of a high percentage of epithelial cells (89.1%), but also immune (6.2%) and stromal (4.7%) cells with peculiar cellular proportions in different sites of the airways. It reveals differential gene expression between identical cell types (suprabasal, secretory, and multiciliated cells) from the nose (MUC4, PI3, SIX3) and tracheobronchial (SCGB1A1, TFF3) airways. By contrast, cell-type specific gene expression was stable across all tracheobronchial samples. Our atlas improves the description of ionocytes, pulmonary neuro-endocrine (PNEC) and brush cells, which are likely derived from a common population of precursor cells. We also report a population of KRT13 positive cells with a high percentage of dividing cells which are reminiscent of “hillock” cells previously described in mouse. Robust characterization of this unprecedented large single-cell cohort establishes an important resource for future investigations. The precise description of the continuum existing from nasal epithelium to successive divisions of lung airways and the stable gene expression profile of these regions better defines conditions under which relevant tracheobronchial proxies of human respiratory diseases can be developed.","abstract":"The respiratory tract constitutes an elaborated line of defense based on a unique cellular ecosystem. Single-cell profiling methods enable the investigation of cell population distributions and transcriptional changes along the airways. We have explored cellular heterogeneity of the human airway epithelium in 10 healthy living volunteers by single-cell RNA profiling. 77,969 cells were collected by bronchoscopy at 35 distinct locations, from the nose to the 12th division of the airway tree. The resulting atlas is composed of a high percentage of epithelial cells (89.1%), but also immune (6.2%) and stromal (4.7%) cells with peculiar cellular proportions in different sites of the airways. It reveals differential gene expression between identical cell types (suprabasal, secretory, and multiciliated cells) from the nose (MUC4, PI3, SIX3) and tracheobronchial (SCGB1A1, TFF3) airways. By contrast, cell-type specific gene expression was stable across all tracheobronchial samples. Our atlas improves the description of ionocytes, pulmonary neuro-endocrine (PNEC) and brush cells, which are likely derived from a common population of precursor cells. We also report a population of KRT13 positive cells with a high percentage of dividing cells which are reminiscent of “hillock” cells previously described in mouse. Robust characterization of this unprecedented large single-cell cohort establishes an important resource for future investigations. The precise description of the continuum existing from nasal epithelium to successive divisions of lung airways and the stable gene expression profile of these regions better defines conditions under which relevant tracheobronchial proxies of human respiratory diseases can be developed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-04T10:53:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004083","title":"Cyprus_Samples_AML_WGS","description":"Sequencing of AML samples to identify mutations that can then be tracked on pre-AML DNA","abstract":"Sequencing of AML samples to identify mutations that can then be tracked on pre-AML DNA","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004084","title":"Whole Exome Sequencing of Spanish Patients diagnosed with rare ophtalmogenetic disorders: Macular Dystrophy, Retinitis Pigmentosa and Leber's congenital amaurosis.","description":null,"abstract":"Whole exome sequencing of Spanish patients suffering from a rare genetic eye disease.  The study was carried out in 2016 as a part of a public call from CNAG (Centro Nacional de Análisis Genómico), where data of ten spanish families were sent to analyse with NGS techniques. The study concluded with four solved cases: one with Macular Dystrophy, one with Retinitis Pigmentosa and two with Leber's congenital amaurosis.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-04T14:56:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004085","title":"Single-cell RNA sequencing of 22 Hodgkin lymphoma tumors and 5 reactive lymph nodes","description":"Hodgkin lymphoma (HL) is characterized by an extensively dominant tumor microenvironment (TME) composed of different types of non-cancerous immune cells with rare malignant cells. Characterization of the cellular components and their spatial relationship is crucial to understanding crosstalk and therapeutic targeting in the TME. We performed single-cell RNA sequencing of more than 127,000 cells from 22 HL tissue specimens and 5 reactive lymph nodes, profiling for the first time the phenotype of the HL-specific immune microenvironment at single-cell resolution. Library preparation was performed using the 10x Genomics Chromium system, and Illumina sequencing was used to generate 3' gene expression data for every cell. Downstream analysis was performed in R to identify HL-specific microenvironment patterns and identify novel cell populations.","abstract":"Hodgkin lymphoma (HL) is characterized by an extensively dominant tumor microenvironment (TME) composed of different types of non-cancerous immune cells with rare malignant cells. Characterization of the cellular components and their spatial relationship is crucial to understanding crosstalk and therapeutic targeting in the TME. We performed single-cell RNA sequencing of more than 127,000 cells from 22 HL tissue specimens and 5 reactive lymph nodes, profiling for the first time the phenotype of the HL-specific immune microenvironment at single-cell resolution. Library preparation was performed using the 10x Genomics Chromium system, and Illumina sequencing was used to generate 3' gene expression data for every cell. Downstream analysis was performed in R to identify HL-specific microenvironment patterns and identify novel cell populations.","study_type":"Other","pubmed_ids":[31857391],"external_links":null,"is_released":true,"released_date":"2019-12-04T22:15:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004086","title":"Whole exome sequencing of advanced gastric cancer","description":"To define the cellular characteristics of malignant ascites of advanced gastric cancer patients and search for therapeutic strategies, we obtained 5 malignant ascites and 1 cerebrospinal fluid from five patients with gastric cancer. We analyzed 180 cells from 4 malignant ascites and 1 cerebrospinal fluid metastasis. The results indicate that the anti-inflammatory characteristics of the tumor associated macrophages are concocted by the tumor cells. By constructing reference transcriptomes for M1 and M2 type macrophages, we found a strong non-inflammatory property of macrophages recovered from the malignant ascites of gastric cancer.","abstract":"To define the cellular characteristics of malignant ascites of advanced gastric cancer patients and search for therapeutic strategies, we obtained 5 malignant ascites and 1 cerebrospinal fluid from five patients with gastric cancer. We analyzed 180 cells from 4 malignant ascites and 1 cerebrospinal fluid metastasis. The results indicate that the anti-inflammatory characteristics of the tumor associated macrophages are concocted by the tumor cells. By constructing reference transcriptomes for M1 and M2 type macrophages, we found a strong non-inflammatory property of macrophages recovered from the malignant ascites of gastric cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-05T01:19:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004087","title":"Multiple Sclerosis risk variants regulate gene expression in innate and adaptive immune cells","description":"Each of at least 200 single nucleotide polymorphisms (SNPs) have been confirmed to be associated with individually small increases in the risk of Multiple Sclerosis (MS).  A key function that could mediate SNP encoded MS risk is their regulatory effects on gene expression or splicing. \n\nTranscriptomic profiling was performed using Affymetrix gene-expression microarrays, using RNA extracted from purified human peripheral blood monocytes, CD4 and CD8 positive lymphocyte cells, B-lymphocyte cells and Natural Killer cells from 73 untreated MS cases and 97 healthy controls.  Cis expression quantitative trait locus (eQTL) mapping studies were performed in each cell type separately to characterize MS risk loci associated with gene expression change.","abstract":"Each of at least 200 single nucleotide polymorphisms (SNPs) have been confirmed to be associated with individually small increases in the risk of Multiple Sclerosis (MS).  A key function that could mediate SNP encoded MS risk is their regulatory effects on gene expression or splicing. \n\nTranscriptomic profiling was performed using Affymetrix gene-expression microarrays, using RNA extracted from purified human peripheral blood monocytes, CD4 and CD8 positive lymphocyte cells, B-lymphocyte cells and Natural Killer cells from 73 untreated MS cases and 97 healthy controls.  Cis expression quantitative trait locus (eQTL) mapping studies were performed in each cell type separately to characterize MS risk loci associated with gene expression change.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-05T03:38:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004088","title":"Rapid response of APC/TP53/KRAS mutated stage IV colorectal cancer under FOLFIRI + Bevacizumab detected by liquid biopsy: a case report","description":"In our non-interventional liquid biopsy study, a male patient in his fifties diagnosed with stage IV colorectal cancer and polytope liver metastases rapidly progressed after completing chemotherapy and deceased 8 months after diagnosis. Retrospective cell free DNA testing showed that the APC/TP53/KRAS major clone responded quickly after 3 cycles of FOLFIRI + Bevacizumab. Retrospective exome sequencing of pre-chemotherapy and post-chemotherapy tissue samples including metastases confirmed that the APC/TP53/KRAS and other major clonal mutations (GPR50, SLC5A, ZIC3, SF3A1 and others) were present in all samples. After the last chemotherapy cycle,","abstract":"In our non-interventional liquid biopsy study, a male patient in his fifties diagnosed with stage IV colorectal cancer and polytope liver metastases rapidly progressed after completing chemotherapy and deceased 8 months after diagnosis. Retrospective cell free DNA testing showed that the APC/TP53/KRAS major clone responded quickly after 3 cycles of FOLFIRI + Bevacizumab. Retrospective exome sequencing of pre-chemotherapy and post-chemotherapy tissue samples including metastases confirmed that the APC/TP53/KRAS and other major clonal mutations (GPR50, SLC5A, ZIC3, SF3A1 and others) were present in all samples. After the last chemotherapy cycle,","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-05T13:29:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004089","title":"HCA_Adrenal_Foetal_WSSS_RNA_SB","description":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess human development. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs).\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess human development. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs).\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-05T15:05:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004090","title":"HNSCC RNA-seq","description":null,"abstract":"The aim of this study was to obtain RNA expression profiles of head and neck squamous cell carcinoma (HNSCC) and to test the prognostic value of known and newly developed gene expression signatures.  polyA mRNA sequencing was performed on HNSCC biopsy material obtained prior to chemoradiotherapy.","study_type":"RNASeq","pubmed_ids":[31027242,31515237],"external_links":null,"is_released":true,"released_date":"2019-12-05T16:33:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004091","title":"HNSCC copy number alterations","description":null,"abstract":"The aim of this study was to characterize copy number alterations (CNA) in advanced head and neck squamous cell carcinoma (HNSCC).  The study data were used to test associations of CNA signatures with patient survival and includes CNA data from hypopharyngeal, laryngeal and HPV-negative oropharyngeal HNSCC.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-05T16:33:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004092","title":"Mitochondrial DNA sequencing in samples of Huntington’s disease patients","description":"Mitochondrial dysfunction is found in the brain and peripheral tissues of Huntington’s disease (HD) patients, which connects many pathological features of HD. In this project, we conducted a large-scale study of mtDNA variations with a sensitive mtDNA-targeted sequencing method called STAMP, at a median coverage of 4000-fold, in lymphoblast and blood samples of HD patients. mtDNA sequence variations and copy numbers were compared between samples from HD patients and healthy control individuals, and were assessed in relation to HD stages, and changes of HD phenotypes in longitudinal samples.","abstract":"Mitochondrial dysfunction is found in the brain and peripheral tissues of Huntington’s disease (HD) patients, which connects many pathological features of HD. In this project, we conducted a large-scale study of mtDNA variations with a sensitive mtDNA-targeted sequencing method called STAMP, at a median coverage of 4000-fold, in lymphoblast and blood samples of HD patients. mtDNA sequence variations and copy numbers were compared between samples from HD patients and healthy control individuals, and were assessed in relation to HD stages, and changes of HD phenotypes in longitudinal samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-05T19:18:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004093","title":"Comparison of structural variations from 10X Genomics linked-reads and conventional Illumina short-reads sequencing","description":"Structural variations (SVs) are large genomic rearrangements that can drive many diseases. Conventional short-reads whole genome sequencing (cWGS) allows their identification with base-pair resolution, but suffers from high false discovery rate. cWGS taps in short-range information from short-reads while linked-reads sequencing (10XWGS) utilizes long-range information. 10XWGS allows linkage of short-reads originating from the same large DNA molecule with a unique barcode captured in a gel bead in emulsion. This mitigates alignment-based artefacts from cWGS especially in repetitive regions. However, the false discovery rate of this technology is unclear. In this study, we performed a comprehensive analysis of different type and size of SVs predicted from these two technologies. The SVs common between both technologies were found to be highly specific by PCR and Sanger sequencing while validation rate dropped for uncommon events. Further, we propose a novel enrichment approach for filtering out false positive calls from both the technologies independently. To this end, we trained a machine learning model for respective technologies and used it to characterise SVs from MCF7 cell line and a primary breast cancer tumor with high precision. This approach would be valuable in understanding true mechanisms driven by SVs in various diseases.","abstract":"Structural variations (SVs) are large genomic rearrangements that can drive many diseases. Conventional short-reads whole genome sequencing (cWGS) allows their identification with base-pair resolution, but suffers from high false discovery rate. cWGS taps in short-range information from short-reads while linked-reads sequencing (10XWGS) utilizes long-range information. 10XWGS allows linkage of short-reads originating from the same large DNA molecule with a unique barcode captured in a gel bead in emulsion. This mitigates alignment-based artefacts from cWGS especially in repetitive regions. However, the false discovery rate of this technology is unclear. In this study, we performed a comprehensive analysis of different type and size of SVs predicted from these two technologies. The SVs common between both technologies were found to be highly specific by PCR and Sanger sequencing while validation rate dropped for uncommon events. Further, we propose a novel enrichment approach for filtering out false positive calls from both the technologies independently. To this end, we trained a machine learning model for respective technologies and used it to characterise SVs from MCF7 cell line and a primary breast cancer tumor with high precision. This approach would be valuable in understanding true mechanisms driven by SVs in various diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-06T10:57:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004094","title":"Single_cell_RNA_analysis_of_human_midbrain_model","description":"The proposed project aims to pioneer 3D brain organoids of a specific brain region known as the “midbrain” that is important in controlling movement in humans, to model the parkinsonian disorder Dopamine Transporter Deficiency Syndrome (DTDS), caused by bi-allelic mutations in SLC6A3.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The study of diseases associated with the human central nervous system (CNS) has been particularly challenging given its’ relative inaccessibility at almost all stages of neurodevelopment. Human induced pluripotent stem cells (hIPSCs) now offer an invaluable tool to study such human diseases. Several protocols have been published for differentiation of hIPSCs into different neuronal sub-populations. However, these 2D culture systems do not satisfactorily recapitulate the cellular and structural complexity.\nThe proposed project aims to pioneer 3D brain organoids of a specific brain region known as the “midbrain” that is important in controlling movement in humans, to model the parkinsonian disorder Dopamine Transporter Deficiency Syndrome (DTDS), caused by bi-allelic mutations in SLC6A3.\nBoth 3D midbrain organoids and 2D differentiated neural cultures from control and DTDS derived IPSC lines will be compared to human fetal samples at different developmental stages using Single-cell RNA-sequencing. This will allow us to identify disease markers, key disease pathways and understand the role of the different cellular subtypes in the progression of DTDS, ultimately aiding in the development of precision disease-specific therapies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004095","title":"HCA_Bone_Foetal_WSSS_RNA_SB","description":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess human development. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs).\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess human development. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs).\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004097","title":"Evolutionary Origins of Recurrent Pancreatic Cancer","description":"Surgery is the only curative option for patients with Stage I/II pancreatic cancer, nonetheless most patients will recur after surgery and die of their disease. To identify novel opportunities for management of recurrent pancreatic cancer we performed whole exome or targeted sequencing of 10 resected primary cancers and their matched intrapancreatic recurrences or distant metastases. We identified that recurrent disease develops from a monophyletic or polyphyletic origin, and this distinction has potential clinical relevance.  In all patients, treatment induced genetic bottlenecks led to a modified genetic landscape and subclonal heterogeneity for driver gene alterations in part due to intermetastatic seeding.  In one patient what was believed to be recurrent disease was an independent (second) primary tumor. These findings strongly advocate for routine post-treatment sampling in the management of recurrent pancreatic cancer.","abstract":"Surgery is the only curative option for patients with Stage I/II pancreatic cancer, nonetheless most patients will recur after surgery and die of their disease. To identify novel opportunities for management of recurrent pancreatic cancer we performed whole exome or targeted sequencing of 10 resected primary cancers and their matched intrapancreatic recurrences or distant metastases. We identified that recurrent disease develops from a monophyletic or polyphyletic origin, and this distinction has potential clinical relevance.  In all patients, treatment induced genetic bottlenecks led to a modified genetic landscape and subclonal heterogeneity for driver gene alterations in part due to intermetastatic seeding.  In one patient what was believed to be recurrent disease was an independent (second) primary tumor. These findings strongly advocate for routine post-treatment sampling in the management of recurrent pancreatic cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-07T01:32:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004098","title":"Deciphering_myeloid_landscape_of_non_small_cell_lung_cancer","description":"We will combine state-of-the-art single-cell experimental data generation with computational analysis using novel methods to reveal the full spectrum of transcriptional and epigenetic changes that are associated with myeloid progenitors’ migration and differentiation at the tumour sites. We anticipate that the results from this study will allow characterisation and subdivision of specific MDSC subtypes and provide novel targets to modulate MDSCs accumulation and/or immunosuppressive activity.\n\nThis project will utilise the comprehensive single-cell transcriptome and chromatin accessibility analysis of tumour-associated immune cells, combined with in vitro functional assays, to reveal the molecular programmes that are active during differentiation of myeloid progenitors to myeloid-derived suppressor cells (MDSCs). The results from this study will identify novel targets to modulate accumulation, differentiation and immunosuppressive function of MDSCs and discover new markers for their prospective isolation. Perturbation of MDSCs will provide means to target tumorigenesis and metastases in lung cancer.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We will combine state-of-the-art single-cell experimental data generation with computational analysis using novel methods to reveal the full spectrum of transcriptional and epigenetic changes that are associated with myeloid progenitors’ migration and differentiation at the tumour sites. We anticipate that the results from this study will allow characterisation and subdivision of specific MDSC subtypes and provide novel targets to modulate MDSCs accumulation and/or immunosuppressive activity.\n\nThis project will utilise the comprehensive single-cell transcriptome and chromatin accessibility analysis of tumour-associated immune cells, combined with in vitro functional assays, to reveal the molecular programmes that are active during differentiation of myeloid progenitors to myeloid-derived suppressor cells (MDSCs). The results from this study will identify novel targets to modulate accumulation, differentiation and immunosuppressive function of MDSCs and discover new markers for their prospective isolation. Perturbation of MDSCs will provide means to target tumorigenesis and metastases in lung cancer.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004099","title":"RNA_sequencing_analysis_of_Plasmodium_falciparum_extracellular_vesicles","description":"Plasmodium falciparum secretes nano-sized vesicles into its extracellular milieu. These vesicles contain biologically active components such as proteins and RNA, and can be transferred to target cells in the host impacting their function. In this project, we aim to understand this mechanism of malaria pathogenesis by describing the RNA content of P.falciparum extracellular vesicles. There are two types of experiments in this project. In the first experiment, both whole parasite and extracellular vesicle RNA were purified from laboratory isolates and ex-vivo matured parasites. The second set of RNA samples were purified from extracellular vesicles isolated from acute malaria plasma samples. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"RNA sequencing analysis of Plasmodium falciparum extracellular vesicles","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004100","title":"Orphan_Tumour_Study___WES","description":"Whole exome sequencing study aiming to uncover the developmental histories of ultra rare childhood tumours.","abstract":"Whole exome sequencing study aiming to uncover the developmental histories of ultra rare childhood tumours.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004101","title":"The genomic landscape of metastatic papillary thyroid carcinoma and novel biomarkers for predicting distant metastasis","description":"Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid gland with arelatively high cure rate. Distant metastasis (DM) of PTC is uncommon, but when it occurs, itsignificantly decreases the survival of PTC patients. However, the molecular mechanisms of DMin PTCs have not been systematically studied. We performed whole exome sequencing andGeneseeqPrime (425 genes) panel sequencing of the primary tumor, plasma and matched whiteblood cell samples from 20 PTCs with DM and 46 PTCs without DM. We identified somaticmutations, gene fusions and copy number alterations and analyzed their relationships with DM ofPTCs. BRAF-V600E was identified in 73% of PTCs, followed by RET fusions (14%) in a mutuallyexclusive manner (p&lt;0.0001). We found gene fusions (RET, ALK or NTRK1) (p&lt;0.01) andchromosome 22q loss(p&lt;0.01) were independently associated with DM by both univariate andmultivariate analysis. A nomogram model consisting of chromosome 22q loss, gene fusions andthree clinical variables was built for predicting DM in PTC (C-index=0.89).The plasma circulatingtumor DNA (ctDNA) detection rate in PTCs was only 38.9%, however, it was significantlyassociated with the metastatic status (p= 0.04), tumor size (p= 0.001) and invasiveness (p= 0.01).In conclusion, gene fusions and chromosome 22q loss were independently associated with DM inPTCs and could serve as molecular biomarkers for predicting DM. The ctDNA detection rate waslow in non-DM PTCs but significantly higher in PTCs with DM.","abstract":"Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid gland with arelatively high cure rate. Distant metastasis (DM) of PTC is uncommon, but when it occurs, itsignificantly decreases the survival of PTC patients. However, the molecular mechanisms of DMin PTCs have not been systematically studied. We performed whole exome sequencing andGeneseeqPrime (425 genes) panel sequencing of the primary tumor, plasma and matched whiteblood cell samples from 20 PTCs with DM and 46 PTCs without DM. We identified somaticmutations, gene fusions and copy number alterations and analyzed their relationships with DM ofPTCs. BRAF-V600E was identified in 73% of PTCs, followed by RET fusions (14%) in a mutuallyexclusive manner (p&lt;0.0001). We found gene fusions (RET, ALK or NTRK1) (p&lt;0.01) andchromosome 22q loss(p&lt;0.01) were independently associated with DM by both univariate andmultivariate analysis. A nomogram model consisting of chromosome 22q loss, gene fusions andthree clinical variables was built for predicting DM in PTC (C-index=0.89).The plasma circulatingtumor DNA (ctDNA) detection rate in PTCs was only 38.9%, however, it was significantlyassociated with the metastatic status (p= 0.04), tumor size (p= 0.001) and invasiveness (p= 0.01).In conclusion, gene fusions and chromosome 22q loss were independently associated with DM inPTCs and could serve as molecular biomarkers for predicting DM. The ctDNA detection rate waslow in non-DM PTCs but significantly higher in PTCs with DM.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004102","title":"SDH_deficient_renal_tumours___WGS_","description":"Succinate dehydrogenase (SDH) deficient renal cancers are a rare and understudied subtype of renal cancer. As such they represent an unmet need in kidney cancer research. Here, we seek to describe the genomics and transcriptomics of SDH deficient renal cancers by sequencing five such tumours. We document their mutational burden, define driver mutations, demonstrate typical patterns of structural variants, and estimate the cell of origin and cellular composition.","abstract":"Succinate dehydrogenase (SDH) deficient renal cancers are a rare and understudied subtype of renal cancer. As such they represent an unmet need in kidney cancer research. Here, we seek to describe the genomics and transcriptomics of SDH deficient renal cancers by sequencing five such tumours. We document their mutational burden, define driver mutations, demonstrate typical patterns of structural variants, and estimate the cell of origin and cellular composition.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-09T15:58:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004103","title":"SDH_deficient_renal_tumours___RNA_","description":"Succinate dehydrogenase (SDH) deficient renal cancers are a rare and understudied subtype of renal cancer. As such they represent an unmet need in kidney cancer research. Here, we seek to describe the genomics and transcriptomics of SDH deficient renal cancers by sequencing five such tumours. We document their mutational burden, define driver mutations, demonstrate typical patterns of structural variants, and estimate the cell of origin and cellular composition.","abstract":"Succinate dehydrogenase (SDH) deficient renal cancers are a rare and understudied subtype of renal cancer. As such they represent an unmet need in kidney cancer research. Here, we seek to describe the genomics and transcriptomics of SDH deficient renal cancers by sequencing five such tumours. We document their mutational burden, define driver mutations, demonstrate typical patterns of structural variants, and estimate the cell of origin and cellular composition.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-09T16:07:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004104","title":"Transcriptome and methylome analysis reveal three cellular origins in the pituitary neuroendocrine tumors","description":null,"abstract":"In this work we carried out whole transcriptome and methylome analysis from 42 Pituitary Neuroendocrine tumors (Pit-NET), comprising 20 non-functioning (NF) Pit-NET, 10 GH Pit-NET, 6 ACTH Pit-NET, 4 TSH Pit-NET and 2 PRL Pit-NET, and 6 control pituitary gland, plus two technical replicas. \nIdentify transcritome profiles of the Pit-NET lesions.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004105","title":"Matched white blood cell and cell-free DNA analyses for detection of minimal residual disease in patients with gastric cancer","description":null,"abstract":"Liquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from clonal hematopoiesis.  Here, we identify circulating tumor-derived DNA alterations (ctDNA) through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient.  We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized controlled study of perioperative chemotherapy in patients with operable gastric cancer.  After filtering alterations derived from matched white-blood cells, the presence of ctDNA predicts recurrence when analyzed within nine weeks after preoperative treatment and after surgery in patients eligible for multimodal treatment.  These analyses provide a facile method for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004106","title":"Comprehensive pharmacogenomic characterization of gastric cancer","description":"Gastric cancer is among the most lethal human malignancies. Previous studies have identified molecular aberrations that constitute dynamic biological networks and genomic complexities of gastric tumors. However, the clinical translation of molecular-guided targeted therapy is hampered by challenges. Notably, solid tumors often harbor multiple genetic alterations, complicating the development of effective treatments. To address such challenges, we established a comprehensive dataset of molecularly annotated patient derivatives coupled with pharmacological profiles for 60 targeted agents to explore dynamic pharmacogenomic interactions in gastric cancers. We identified lineage-specific drug sensitivities based on histopathological and molecular subclassification, including substantial sensitivities toward VEGFR and EGFR inhibition therapies in diffuse- and signet ring-type gastric tumors, respectively. We identified potential therapeutic opportunities for WNT pathway inhibitors in ALK-mutant tumors, a significant association between PIK3CA-E542K mutation and AZD5363 response, and transcriptome expression of RNF11 as a potential predictor of response to gefitinib. Collectively, our results demonstrate the feasibility of drug screening combined with tumor molecular characterization to facilitate personalized therapeutic regimens for gastric tumors.","abstract":"Gastric cancer is among the most lethal human malignancies. Previous studies have identified molecular aberrations that constitute dynamic biological networks and genomic complexities of gastric tumors. However, the clinical translation of molecular-guided targeted therapy is hampered by challenges. Notably, solid tumors often harbor multiple genetic alterations, complicating the development of effective treatments. To address such challenges, we established a comprehensive dataset of molecularly annotated patient derivatives coupled with pharmacological profiles for 60 targeted agents to explore dynamic pharmacogenomic interactions in gastric cancers. We identified lineage-specific drug sensitivities based on histopathological and molecular subclassification, including substantial sensitivities toward VEGFR and EGFR inhibition therapies in diffuse- and signet ring-type gastric tumors, respectively. We identified potential therapeutic opportunities for WNT pathway inhibitors in ALK-mutant tumors, a significant association between PIK3CA-E542K mutation and AZD5363 response, and transcriptome expression of RNF11 as a potential predictor of response to gefitinib. Collectively, our results demonstrate the feasibility of drug screening combined with tumor molecular characterization to facilitate personalized therapeutic regimens for gastric tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-11T04:27:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004107","title":"Single cell RNA seq of the developing human embryo brain","description":"The study aims at identifying the cell types and lineages of the developing human brain.","abstract":"The study aims at identifying the cell types and lineages of the developing human brain.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-11T12:34:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004108","title":"54 metastatic colorectal cancer patients from Schleswig-Holstein in North Germany","description":"Personalized treatment vs standard of care is much debated, especially in clinical practice. Here we investigated whether overall survival differences in metastatic colorectal cancer patients are explained by their tumor mutation profiles or by their treatment differences in real clinical practice.","abstract":"Personalized treatment vs standard of care is much debated, especially in clinical practice. Here we investigated whether overall survival differences in metastatic colorectal cancer patients are explained by their tumor mutation profiles or by their treatment differences in real clinical practice.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-11T14:54:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004109","title":"Cancer modeling in colorectal organoids reveals intrinsic differences between oncogenic RAS and BRAF variants","description":null,"abstract":"Colorectal cancers (CRCs) with oncogenic mutations in RAS and BRAF are associated with anti-EGFR therapy resistance. Consequently, all RAS mutant CRC patients are being excluded from this therapy. However, heterogeneity in drug response has been reported between RAS mutant CRC patients. It is poorly understood to what extent such differences are derived from different genetic backgrounds or intrinsic differences between the various RAS pathway mutations. Therefore, using CRISPR technology we generated an isogenic panel of patient-derived CRC organoids with various RAS pathway mutations (i.e. KRASG12D, BRAFV600E­­, KRASG13D and NRASG12D). All RAS pathway mutants promote ERK activation and tumor growth. However, KRASG12D and BRAFV600E­­ mutations in particular conferred robust resistance to anti-EGFR therapy, both in vitro and in vivo. Moreover, untreated KRASG13D mutants showed fastest growth in mice but remained sensitive to anti-EGFR therapy. Together, introducing mutation-specific oncogene signaling in CRC organoids resembles clinical phenotypes and improves understanding of genotype-phenotype correlations.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004110","title":"Exon4-mutations in KRAS Affect MEK-ERK and Pi3K-AKT Signaling in Multiple Myeloma","description":"Approximately 40% of MM cases harbor a point mutation in either KRAS or NRAS. However, it is still unclear whether RAS-mutations are associated with disease outcome. Specifically, no information exists whether KRAS-mutations have an impact on survival in MM patients at diagnosis that were treated with novel agents (e.g. bortezomib, lenalidomide). Targeting KRAS directly for therapeutic purposes is still impossible, but recently the first covalent mutant-specific inhibitor targeting KRASG12C made it into clinical trials. However, other KRAS-hotspot-mutations exist in MM patients, including the less common exon4-mutations. Within the current study, the coding regions of KRAS in 80 MM patients at diagnosis, uniformly treated with bortezomib and high-dose chemotherapy, were deep-sequenced. Moreover, the functional impact of KRASG12A as well as the two exon4-mutations A146T (AMO1) and A146V (MM patient) on different survival pathways was investigated. Specifically, an siRNA-mediated knockdown in AMO1 was performed and KRASWT, KRASG12A, KRAS146T and KRAS146V were overexpressed in the KRASWT cell lines JJN3 and OPM2 using lentiviral transduction and the transposase based Sleeping Beauty system. KRAS-mutations were not associated with survival. Yet, the expression of all KRAS-mutants had an impact on MEK/ERK-signaling in two independent MM cell lines and on AKT/PI3K-signaling in one MM cell line.","abstract":"Approximately 40% of MM cases harbor a point mutation in either KRAS or NRAS. However, it is still unclear whether RAS-mutations are associated with disease outcome. Specifically, no information exists whether KRAS-mutations have an impact on survival in MM patients at diagnosis that were treated with novel agents (e.g. bortezomib, lenalidomide). Targeting KRAS directly for therapeutic purposes is still impossible, but recently the first covalent mutant-specific inhibitor targeting KRASG12C made it into clinical trials. However, other KRAS-hotspot-mutations exist in MM patients, including the less common exon4-mutations. Within the current study, the coding regions of KRAS in 80 MM patients at diagnosis, uniformly treated with bortezomib and high-dose chemotherapy, were deep-sequenced. Moreover, the functional impact of KRASG12A as well as the two exon4-mutations A146T (AMO1) and A146V (MM patient) on different survival pathways was investigated. Specifically, an siRNA-mediated knockdown in AMO1 was performed and KRASWT, KRASG12A, KRAS146T and KRAS146V were overexpressed in the KRASWT cell lines JJN3 and OPM2 using lentiviral transduction and the transposase based Sleeping Beauty system. KRAS-mutations were not associated with survival. Yet, the expression of all KRAS-mutants had an impact on MEK/ERK-signaling in two independent MM cell lines and on AKT/PI3K-signaling in one MM cell line.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-12T13:49:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004111","title":"Y chromosome variability in Polish population","description":"The aim of the present study was to define the Y chromosome variability in Polish male population. For the first time, the study of Polish population was conducted on such a large number of individuals (n=2705) representing administrative units of both levels of local administration in Poland (voivodeships and counties). Furthermore, the clusters were used as an additional form of population subdivision, corresponding to geographic regions of Poland.","abstract":"The aim of the present study was to define the Y chromosome variability in Polish male population. For the first time, the study of Polish population was conducted on such a large number of individuals (n=2705) representing administrative units of both levels of local administration in Poland (voivodeships and counties). Furthermore, the clusters were used as an additional form of population subdivision, corresponding to geographic regions of Poland.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-12T15:42:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004112","title":"Reference Exome Data for a Northern Brazilian population","description":"Whole exome sequencing (WES) is a popular technology widely used in the diagnosis of rare genetic diseases and provides useful variant data for analysis of complex diseases.  However, there is not always adequate population-specific reference data available to assist clinical geneticists in assigning a diagnostic variant to a specific clinical condition.  Here we provide a catalogue of variants called after sequencing the exomes of 45 babies from the State of Rio Grande do Nord in Brazil.  Sequence data were processed using an ‘intersect-then-combine’ (ITC) approach, using GATK and SAMtools to call variants.   A total of 612,761 variants were identified in at least one individual in this Brazilian Cohort, including 559,448 single nucleotide variants (SNVs) and 53,313 insertion/deletions.  Of these, 58,111 overlapped with nonsynonymous (nsSNVs) or splice site (ssSNVs) SNVs in dbNSFP.  As an aid to clinical diagnosis of rare diseases, we used the American College of Medicine Genetics and Genomics (ACMG) guidelines to assign pathogenic/likely pathogenic status to 439 (0.755%) of the 58,111 nsSNVs and ssSNVs.  Our data set provides a useful reference point for diagnosis of rare diseases in Brazil.","abstract":"Whole exome sequencing (WES) is a popular technology widely used in the diagnosis of rare genetic diseases and provides useful variant data for analysis of complex diseases.  However, there is not always adequate population-specific reference data available to assist clinical geneticists in assigning a diagnostic variant to a specific clinical condition.  Here we provide a catalogue of variants called after sequencing the exomes of 45 babies from the State of Rio Grande do Nord in Brazil.  Sequence data were processed using an ‘intersect-then-combine’ (ITC) approach, using GATK and SAMtools to call variants.   A total of 612,761 variants were identified in at least one individual in this Brazilian Cohort, including 559,448 single nucleotide variants (SNVs) and 53,313 insertion/deletions.  Of these, 58,111 overlapped with nonsynonymous (nsSNVs) or splice site (ssSNVs) SNVs in dbNSFP.  As an aid to clinical diagnosis of rare diseases, we used the American College of Medicine Genetics and Genomics (ACMG) guidelines to assign pathogenic/likely pathogenic status to 439 (0.755%) of the 58,111 nsSNVs and ssSNVs.  Our data set provides a useful reference point for diagnosis of rare diseases in Brazil.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-13T06:17:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004113","title":"Lenalidomide Resistance in del(5q) Myelodysplastic Syndrome Follows Loss of RUNX1/TP53-mediated Megakaryocytic Differentiation","description":"Interstitial deletion of the long arm of chromosome 5 (del(5q)) is the commonest structural genomic variant in myelodysplastic syndromes (MDS). Lenalidomide (LEN) is the treatment of choice for patients with del(5q) MDS, but half of the responding patients become resistant within two years. TP53 mutations are detected in ~20% of patients who become resistant to LEN. Our data show that patients who become resistant to LEN harbor either TP53 or RUNX1 mutations or loss of RUNX1 expression. Here we show that LEN-induced degradation of IKZF1 permits a RUNX1/GATA2 complex to drive megakaryocytic differentiation and consequent del(5q) MDS progenitor cell death via CRBN-mediated CSNK1A1 degradation. Overexpression of GATA2 is able to restore LEN sensitivity in the context of RUNX1 or TP53 mutations by enhancing LEN-induced megakaryocytic differentiation. Screening for TP53 and RUNX1 mutations or downregulation should identify patients resistant to LEN, and strategies to activate GATA2 may resensitize del(5q) MDS cells to LEN","abstract":"Interstitial deletion of the long arm of chromosome 5 (del(5q)) is the commonest structural genomic variant in myelodysplastic syndromes (MDS). Lenalidomide (LEN) is the treatment of choice for patients with del(5q) MDS, but half of the responding patients become resistant within two years. TP53 mutations are detected in ~20% of patients who become resistant to LEN. Our data show that patients who become resistant to LEN harbor either TP53 or RUNX1 mutations or loss of RUNX1 expression. Here we show that LEN-induced degradation of IKZF1 permits a RUNX1/GATA2 complex to drive megakaryocytic differentiation and consequent del(5q) MDS progenitor cell death via CRBN-mediated CSNK1A1 degradation. Overexpression of GATA2 is able to restore LEN sensitivity in the context of RUNX1 or TP53 mutations by enhancing LEN-induced megakaryocytic differentiation. Screening for TP53 and RUNX1 mutations or downregulation should identify patients resistant to LEN, and strategies to activate GATA2 may resensitize del(5q) MDS cells to LEN","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-13T18:31:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004114","title":"White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer","description":"Liquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from clonal hematopoiesis.  Here, we identify circulating tumor-derived DNA alterations (ctDNA) through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient.  We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized controlled study of perioperative chemotherapy in patients with operable gastric cancer.  After filtering alterations derived from matched white-blood cells, the presence of ctDNA predicts recurrence when analyzed within nine weeks after preoperative treatment and after surgery in patients eligible for multimodal treatment.  These analyses provide a facile method for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer.","abstract":"Liquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from clonal hematopoiesis.  Here, we identify circulating tumor-derived DNA alterations (ctDNA) through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient.  We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized controlled study of perioperative chemotherapy in patients with operable gastric cancer.  After filtering alterations derived from matched white-blood cells, the presence of ctDNA predicts recurrence when analyzed within nine weeks after preoperative treatment and after surgery in patients eligible for multimodal treatment.  These analyses provide a facile method for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-15T15:07:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004115","title":"Quality of Whole Genome Sequencing from Blood versus Saliva Derived DNA in Cardiac Patients","description":null,"abstract":"WGS was performed in DNA from 5 paired samples from participants enrolled in a heart disease biorepository. We compared the proportion of sequencing reads that mapped to non-human sources (microbiome), the sequencing coverage, and the yield and concordance of single nucleotide variant (SNV) and copy number variant (CNV) calls between blood and saliva genomes.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-16T15:30:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004116","title":"CD8+ T-cell exhaustion induced by leukemic cells drives progression in Chronic Lymphocytic Leukemia","description":"In order to shed light on mechanisms that lead to CLL progression, we investigated longitudinal changes in both the genetic and immunological landscapes. For that, we analyzed paired samples obtained from CLL patients at diagnosis and progression before front-line treatment or at diagnosis and long-term asymptomatic follow-up. By whole-exome sequencing (WES), we found that CLL cells displayed limited genetic evolution at progression. Conversely, T cells from progressing patients showed significant immunophenotypical and transcriptional changes over time not observed in patients that did not progress. Specifically, we found that CD8+ T cells at progression were characterized by an increasing terminally exhausted effector phenotype (T-betdim/- Eomeshi PD1hi) with high co-expression of inhibitory receptors (PD1, CD244 and CD160). This exhausted status in CD8+ T cells was induced by progressing leukemic cells mainly through a mechanism dependent on soluble factors, including IL-10. Thus, we demonstrate that immunological changes are of paramount importance for CLL clinical progression, thereby providing a rationale for the use of early immunotherapeutic intervention in this disease.","abstract":"In order to shed light on mechanisms that lead to CLL progression, we investigated longitudinal changes in both the genetic and immunological landscapes. For that, we analyzed paired samples obtained from CLL patients at diagnosis and progression before front-line treatment or at diagnosis and long-term asymptomatic follow-up. By whole-exome sequencing (WES), we found that CLL cells displayed limited genetic evolution at progression. Conversely, T cells from progressing patients showed significant immunophenotypical and transcriptional changes over time not observed in patients that did not progress. Specifically, we found that CD8+ T cells at progression were characterized by an increasing terminally exhausted effector phenotype (T-betdim/- Eomeshi PD1hi) with high co-expression of inhibitory receptors (PD1, CD244 and CD160). This exhausted status in CD8+ T cells was induced by progressing leukemic cells mainly through a mechanism dependent on soluble factors, including IL-10. Thus, we demonstrate that immunological changes are of paramount importance for CLL clinical progression, thereby providing a rationale for the use of early immunotherapeutic intervention in this disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-16T15:54:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004117","title":"Genomic landscape of inflammatory breast cancer by whole-genome sequencing","description":"Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer, characterized by a highly invasive and metastatic phenotype, but little is known about its genetic drivers. Here we report whole-genome sequencing (WGS) of 20 newly diagnosed IBC biopsies to characterize for the first time the entire genomic landscape of this disease.","abstract":"Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer, characterized by a highly invasive and metastatic phenotype, but little is known about its genetic drivers. Here we report whole-genome sequencing (WGS) of 20 newly diagnosed IBC biopsies to characterize for the first time the entire genomic landscape of this disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-16T20:22:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004118","title":"Imaging metabolic heterogeneity in breast cancer using hyperpolarized 13C-MRI","description":"Higher 13C-lactate labeling was seen in the more aggressive tumors, including all triple negative breast cancers. There was a significant correlation between lactate labeling and expression of the monocarboxylate transporter (MCT1), which mediates tumor cell pyruvate uptake, and a weaker correlation with expression of LDHA, which catalyzes label exchange between the injected pyruvate and the endogenous lactate pool.","abstract":"Higher 13C-lactate labeling was seen in the more aggressive tumors, including all triple negative breast cancers. There was a significant correlation between lactate labeling and expression of the monocarboxylate transporter (MCT1), which mediates tumor cell pyruvate uptake, and a weaker correlation with expression of LDHA, which catalyzes label exchange between the injected pyruvate and the endogenous lactate pool.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-16T22:54:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004119","title":"WRONG SUBMISSION; UNABLE TO DELETE","description":null,"abstract":"Whole genome sequencing of taiwanese UTUCs and paired normal tissue to assess mutational signatures","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004120","title":"HCA_Immune_Foetal_WSSS_RNA","description":"WSSS developmental immune cell atlas\n\nHuman Developmental Immune Cell Atlas - Foetal RNA work. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"WSSS developmental immune cell atlas\n\nHuman Developmental Immune Cell Atlas - Foetal RNA work. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004121","title":"Germline elongator mutations in sonic hedgehog medulloblastoma (DEPRECATED-DUPLICATE)","description":"Cancer genomics has illuminated a wide spectrum of genes and core molecular processes contributing to human malignancy. Still, the genetic and molecular basis of many cancers remains only partially explained. Genetic predisposition accounts for 5-10% of cancer diagnoses and genetic events cooperating with known somatic driver events are poorly understood.\n\nAnalyzing established cancer predisposition genes in medulloblastoma (MB), a malignant childhood brain tumor, we recently identified pathogenic germline variants that account for 5% of all MB patients.\nHere, by extending our previous analysis to include all protein-coding genes, we discovered and replicated rare germline loss-of-function (LoF) variants across Elongator Complex Protein 1 (ELP1) on 9q31.3 in 15% of pediatric MBSHH cases, thus implicating ELP1 as the most common MB predisposition gene and increasing genetic predisposition to 40% for pediatric MBSHH.\nInheritance was verified based on parent-offspring and pedigree analysis, which identified two families with a history of pediatric MB. ELP1-associated MBs were restricted to the molecular SHHa subtype and were characterized by universal biallelic inactivation of ELP1 due to somatic loss of chromosome 9q.\nThe majority of ELP1-associated MBs exhibited co-occurring somatic PTCH1 (9q22.32) alterations, suggesting that ELP1-deficiency predisposes to tumor development in combination with constitutive activation of SHH signaling. \n\nELP1 is an essential subunit of the evolutionary conserved Elongator complex, whose primary function is to enable efficient translational elongation through tRNAs modifications at the wobble (U34) position.\nBiochemical, transcriptional, and proteomic analyses revealed that ELP1-associated MBSHH are characterized by a destabilized core elongator complex, loss of elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response (UPR), consistent with deregulation of protein homeostasis due to elongator-deficiency in model systems.\n\nOur findings suggest that genetic predisposition to proteome instability is a previously underappreciated determinant in the pathogenesis of pediatric brain cancer. These results provide strong rationale for further investigating the role of protein homeostasis in other pediatric and adult cancer types and potential opportunities for novel therapeutic interference.","abstract":"Cancer genomics has illuminated a wide spectrum of genes and core molecular processes contributing to human malignancy. Still, the genetic and molecular basis of many cancers remains only partially explained. Genetic predisposition accounts for 5-10% of cancer diagnoses and genetic events cooperating with known somatic driver events are poorly understood.\n\nAnalyzing established cancer predisposition genes in medulloblastoma (MB), a malignant childhood brain tumor, we recently identified pathogenic germline variants that account for 5% of all MB patients.\nHere, by extending our previous analysis to include all protein-coding genes, we discovered and replicated rare germline loss-of-function (LoF) variants across Elongator Complex Protein 1 (ELP1) on 9q31.3 in 15% of pediatric MBSHH cases, thus implicating ELP1 as the most common MB predisposition gene and increasing genetic predisposition to 40% for pediatric MBSHH.\nInheritance was verified based on parent-offspring and pedigree analysis, which identified two families with a history of pediatric MB. ELP1-associated MBs were restricted to the molecular SHHa subtype and were characterized by universal biallelic inactivation of ELP1 due to somatic loss of chromosome 9q.\nThe majority of ELP1-associated MBs exhibited co-occurring somatic PTCH1 (9q22.32) alterations, suggesting that ELP1-deficiency predisposes to tumor development in combination with constitutive activation of SHH signaling. \n\nELP1 is an essential subunit of the evolutionary conserved Elongator complex, whose primary function is to enable efficient translational elongation through tRNAs modifications at the wobble (U34) position.\nBiochemical, transcriptional, and proteomic analyses revealed that ELP1-associated MBSHH are characterized by a destabilized core elongator complex, loss of elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response (UPR), consistent with deregulation of protein homeostasis due to elongator-deficiency in model systems.\n\nOur findings suggest that genetic predisposition to proteome instability is a previously underappreciated determinant in the pathogenesis of pediatric brain cancer. These results provide strong rationale for further investigating the role of protein homeostasis in other pediatric and adult cancer types and potential opportunities for novel therapeutic interference.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004122","title":"Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___GI___MAP___WGS","description":"Somatic mutations (burdens and signatures) and clonal dynamics in normal human tissues from the gastrointestinal tract of individuals with tumour predisposition syndromes and DNA damage repair defects.","abstract":"The aim of this project is to investigate somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the study of normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to identify and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-17T15:17:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004123","title":"Benchmarking of ProSolo, a new probabilistic single nucleotide variant caller for single cell DNA sequencing data. This study provides the whole exome sequencing dataset used in this assessment.","description":"Benchmarking of ProSolo, a new probabilistic single nucleotide variant caller for single cell DNA sequencing data that provides control over the false discovery rate of different single cell events at genomic sites (e.g. alternative allele presence or allele dropout). Here, we provide the newly generated whole exome sequencing data used in assessing ProSolo's performance. It contains whole exome sequencing of: a patient with a constitutional mismatch repair defect (MSH6-) and their parents and siblings, a granulocyte bulk sample and 5 single granulocytes sequenced after whole genome amplification.","abstract":"Benchmarking of ProSolo, a new probabilistic single nucleotide variant caller for single cell DNA sequencing data that provides control over the false discovery rate of different single cell events at genomic sites (e.g. alternative allele presence or allele dropout). Here, we provide the newly generated whole exome sequencing data used in assessing ProSolo's performance. It contains whole exome sequencing of: a patient with a constitutional mismatch repair defect (MSH6-) and their parents and siblings, a granulocyte bulk sample and 5 single granulocytes sequenced after whole genome amplification.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-18T17:49:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004124","title":"Genomic_characterisation_of_MGUS__","description":"he hematological malignancy multiple myeloma (MM), also called Kahler’s disease or plasma cell (PC) myeloma, is characterized by a clonal expansion of PCs originating in the bone marrow (BM). The expansion of these cells leads to an overproduction of antibodies and results in typical symptoms such as anemia, renal failure and bone lesions. All cases of MM are preceded by the asymptomatic, non-malignant pre-stage monoclonal gammopathy of undetermined significance (MGUS). Of all MGUS patients, only 1% per year will progress to MM. Despite efforts to elucidate the molecular mechanisms underlying the MGUS-to-MM progression, its pathogenesis still remains largely unknown. Additionally, the genetic profiles of MGUS patients have only been limitedly investigated due to the only incidental finding of MGUS, the difficulties in BM sampling and isolating a sufficient number of aberrant PCs from the BM aspirates of MGUS patients. Consequently, reliable biomarkers to individually predict which MGUS patients will progress to MM and which will not, are lacking. Therefore, it is highly required to study the molecular pathogenesis of MGUS and the role of genetic events in relation to the malignant transformation to MM.","abstract":"he hematological malignancy multiple myeloma (MM), also called Kahler’s disease or plasma cell (PC) myeloma, is characterized by a clonal expansion of PCs originating in the bone marrow (BM). The expansion of these cells leads to an overproduction of antibodies and results in typical symptoms such as anemia, renal failure and bone lesions. All cases of MM are preceded by the asymptomatic, non-malignant pre-stage monoclonal gammopathy of undetermined significance (MGUS). Of all MGUS patients, only 1% per year will progress to MM. Despite efforts to elucidate the molecular mechanisms underlying the MGUS-to-MM progression, its pathogenesis still remains largely unknown. Additionally, the genetic profiles of MGUS patients have only been limitedly investigated due to the only incidental finding of MGUS, the difficulties in BM sampling and isolating a sufficient number of aberrant PCs from the BM aspirates of MGUS patients. Consequently, reliable biomarkers to individually predict which MGUS patients will progress to MM and which will not, are lacking. Therefore, it is highly required to study the molecular pathogenesis of MGUS and the role of genetic events in relation to the malignant transformation to MM.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-18T22:19:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004125","title":"MutWP6__CRUK_Grand_Challenge_Mutographs_of_Cancer__oncology_agents","description":"he Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nWithin Mutographs, work lead by the Sanger Institute will investigate whether detection of somatic mutations and mutational signatures in circulating white blood cells can be developed into a practical, generic system for surveying and monitoring multiple different endogenous and exogenous exposures, providing an ‘observatory’ on somatic mutational processes in humans.\n\nWhole genome sequences are generated at the Wellcome Sanger Institute (Illumina HiSeqX). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"he Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nWithin Mutographs, work lead by the Sanger Institute will investigate whether detection of somatic mutations and mutational signatures in circulating white blood cells can be developed into a practical, generic system for surveying and monitoring multiple different endogenous and exogenous exposures, providing an ‘observatory’ on somatic mutational processes in humans.\n\nWhole genome sequences are generated at the Wellcome Sanger Institute (Illumina HiSeqX). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-19T12:08:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004126","title":"Germline elongator mutations in sonic hedgehog medulloblastoma","description":"Cancer genomics has illuminated a wide spectrum of genes and core molecular processes contributing to human malignancy. Still, the genetic and molecular basis of many cancers remains only partially explained.\nGenetic predisposition accounts for 5-10% of cancer diagnoses and genetic events cooperating with known somatic driver events are poorly understood.\n\nAnalyzing established cancer predisposition genes in medulloblastoma (MB), a malignant childhood brain tumor, we recently identified pathogenic germline variants that account for 5% of all MB patients.\nHere, by extending our previous analysis to include all protein-coding genes, we discovered and replicated rare germline loss-of-function (LoF) variants across Elongator Complex Protein 1 (ELP1) on 9q31.3 in 15% of pediatric MBSHH cases, thus implicating ELP1 as the most common MB predisposition gene and increasing genetic predisposition to 40% for pediatric MBSHH.\n\nInheritance was verified based on parent-offspring and pedigree analysis, which identified two families with a history of pediatric MB. ELP1-associated MBs were restricted to the molecular SHHa subtype and were characterized by universal biallelic inactivation of ELP1 due to somatic loss of chromosome 9q.\nThe majority of ELP1-associated MBs exhibited co-occurring somatic PTCH1 (9q22.32) alterations, suggesting that ELP1-deficiency predisposes to tumor development in combination with constitutive activation of SHH signaling. \n\nELP1 is an essential subunit of the evolutionary conserved Elongator complex, whose primary function is to enable efficient translational elongation through tRNAs modifications at the wobble (U34) position.\nBiochemical, transcriptional, and proteomic analyses revealed that ELP1-associated MBSHH are characterized by a destabilized core Elongator complex, loss of Elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response (UPR), consistent with deregulation of protein homeostasis due to Elongator-deficiency in model systems.\n\nOur findings suggest that genetic predisposition to proteome instability is a previously underappreciated determinant in the pathogenesis of pediatric brain cancer. These results provide strong rationale for further investigating the role of protein homeostasis in other pediatric and adult cancer types and potential opportunities for novel therapeutic interference.","abstract":"Cancer genomics has illuminated a wide spectrum of genes and core molecular processes contributing to human malignancy. Still, the genetic and molecular basis of many cancers remains only partially explained.\nGenetic predisposition accounts for 5-10% of cancer diagnoses and genetic events cooperating with known somatic driver events are poorly understood.\n\nAnalyzing established cancer predisposition genes in medulloblastoma (MB), a malignant childhood brain tumor, we recently identified pathogenic germline variants that account for 5% of all MB patients.\nHere, by extending our previous analysis to include all protein-coding genes, we discovered and replicated rare germline loss-of-function (LoF) variants across Elongator Complex Protein 1 (ELP1) on 9q31.3 in 15% of pediatric MBSHH cases, thus implicating ELP1 as the most common MB predisposition gene and increasing genetic predisposition to 40% for pediatric MBSHH.\n\nInheritance was verified based on parent-offspring and pedigree analysis, which identified two families with a history of pediatric MB. ELP1-associated MBs were restricted to the molecular SHHa subtype and were characterized by universal biallelic inactivation of ELP1 due to somatic loss of chromosome 9q.\nThe majority of ELP1-associated MBs exhibited co-occurring somatic PTCH1 (9q22.32) alterations, suggesting that ELP1-deficiency predisposes to tumor development in combination with constitutive activation of SHH signaling. \n\nELP1 is an essential subunit of the evolutionary conserved Elongator complex, whose primary function is to enable efficient translational elongation through tRNAs modifications at the wobble (U34) position.\nBiochemical, transcriptional, and proteomic analyses revealed that ELP1-associated MBSHH are characterized by a destabilized core Elongator complex, loss of Elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response (UPR), consistent with deregulation of protein homeostasis due to Elongator-deficiency in model systems.\n\nOur findings suggest that genetic predisposition to proteome instability is a previously underappreciated determinant in the pathogenesis of pediatric brain cancer. These results provide strong rationale for further investigating the role of protein homeostasis in other pediatric and adult cancer types and potential opportunities for novel therapeutic interference.","study_type":"Other","pubmed_ids":[32296180],"external_links":null,"is_released":true,"released_date":"2019-12-19T14:54:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004127","title":"RNASeq for BMI GL study","description":null,"abstract":"The genetic architecture of the small and isolated Greenlandic population is advantageous for identification of novel genetic variants associated with cardio-metabolic traits. We aimed to identify genetic loci associated with body-mass index (BMI), to expand the knowledge of the genetic and biological mechanisms underlying obesity. Stage 1 BMI-association analyses were performed in 4,674 Greenlanders. Stage 2 replication and meta-analysis were performed in additional cohorts comprising 1,058 Yup’ik Alaska Native people, and 1,529 Greenlanders. Obesity-related traits were assessed in the stage 1 study population, and expression of RNA in blood was assessed in a subset of this population. We identified a common variant on chromosome 11, rs4936356, genome-wide significantly associated with lower BMI (beta (SE), -0.14 SD (0.03), p=3.2x10-8), corresponding to 0.64 kg/m2 lower BMI per G allele in the stage 1 study population. We observed a similar effect in the Yup’ik cohort (-0.09 SD, p=0.038), and a non-significant effect in the same direction in the independent Greenlandic stage 2 cohort (-0.03 SD, p=0.514). The association remained genome-wide significant in meta-analysis of the Arctic cohorts (-0.103 SD (0.02), p=4.7x10-8). Moreover, the variant was associated with a leaner body type (weight, -1.68 (0.37) kg; waist circumference, -1.52 (0.33) cm; hip circumference, -0.85 (0.24) cm; fat percent, -1.39 (0.27) %; lean mass, -0.84 (0.19) kg; visceral adipose tissue, -0.30 (0.07) cm; subcutaneous adipose tissue, -0.16 (0.05) cm, all p&lt;0.0002), lower insulin resistance (HOMA-IR, -0.12 (0.04), p=0.00021), and favorable lipid levels (triglyceride, -0.05 (0.02) mmol/l, p=0.025; HDL-cholesterol, 0.04 (0.01) mmol/l, p=0.0015). Expression analyses of RNA did not reveal any genes regulated by rs4936356 in leukocytes. In conclusion, we identified a novel variant possibly associated with lower BMI, leaner body type, lower insulin resistance, and a favorable lipid profile. The causal transcript in the locus could potentially be a therapeutic target for improving metabolic health.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2019-12-23T08:30:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004128","title":"Discovery_of_immune_cells_and_molecules_involved_in_asthma_remission_","description":"Single cell RNA-sequencing of innate lymphocytes, CD4+ T-cells, CD8+ T-cells, B-cells and bronchial epithelial cells from lung biopsies and of eosinophils from blood of patients with asthma, subjects in clinical or complete asthma remission and healthy controls. Analysis of single-cell RNA sequences in association with detailed clinical phenotypes of the different patient groups.\nDiscovery of immune cells and molecules involved in asthma remission\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Single cell RNA-sequencing of innate lymphocytes, CD4+ T-cells, CD8+ T-cells, B-cells and bronchial epithelial cells from lung biopsies and of eosinophils from blood of patients with asthma, subjects in clinical or complete asthma remission and healthy controls. Analysis of single-cell RNA sequences in association with detailed clinical phenotypes of the different patient groups.\nDiscovery of immune cells and molecules involved in asthma remission\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004129","title":"Molecular profiling of matched presentation-relapse in multiple myeloma","description":null,"abstract":"Gene expression profiling of presentation-relapse samples from 73 patients from the NCRI Myeloma XI using SKY92 MMProfiler (SkylineDx, The Netherlands) expression arrays.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004130","title":"HSC_population_dynamics__scRNA_seq___KX008","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004131","title":"Polyploid hepatocytes are protected from cancer but maintain regenerative capacity in chronic liver disease","description":null,"abstract":"Thirty to ninety percent of hepatocytes contain whole genome duplications, making it imperative to understand the fates and functions of these polyploid cells and how they affect development of liver disease. An important question is how polyploid cells respond to chronic proliferative demands, which are characteristic of liver diseases, but a challenging situation for cells with multiple genomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004132","title":"Baboon_Ancient_African_genomes","description":"Ancient genome of a 5,800 old baboon from southern Africa                                                                                                                                                                                                                                                                                                                                  \n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Ancient genome from a 5,800 year baboon proximal phalanx bone from southern Africa (Ha Makotoko in Lesotho). This study is aimed at determining the population of origin and the degree of continuity in the southern African baboon population.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004133","title":"Immuno_Oncology_Focused_Library_HT29c9","description":"The study will perform loss-of-function CRISPR-Cas9 screens to identify tumour cell regulators of immune effector signaling.","abstract":"The study will perform loss-of-function CRISPR-Cas9 screens to identify tumour cell regulators of immune effector signaling.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004134","title":"HCA_WSSS_Foetal_Lung_RNA","description":"Human Cell Atlas for lung - Foetal RNA work. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions. \n\nWSSS Deep Dive for Foetal Lung RNA only.  This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Human Cell Atlas for lung - Foetal RNA work. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions. \n\nWSSS Deep Dive for Foetal Lung RNA only.  This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004135","title":"Comparison of 133/144bp dominant phenotype vs 166bp dominant phenotype.","description":"Background: Previous studies found that cell-free DNA (cfDNA) generated from tumors was shorter than that from healthy cells, and selecting short cfDNA could enrich for tumor cfDNA and improve its usage in early cancer diagnosis and treatment monitoring; however, the underlying mechanism of shortened tumor cfDNA was still unknown, which potentially limits its further clinical application.Results: Using targeted sequencing of cfDNA in a large cohort of solid tumor patient, sequencing reads harboring tumor-specific somatic mutations were isolated to examine the exact size distribution of tumor cfDNA. For the majority of studied cases, 166bp remained as the peak size of tumor cfDNA, with tumor cfDNA showing an increased proportion of short fragments (100-150bp). Less than 1% of cfDNA samples were found to be peaked at 134/144bp and independent of tumor cfDNA purity. Using whole-genome sequencing of cfDNA, we discovered a positive correlation between cfDNA shortening and the magnitude of chromatin inaccessibility, as measured by transcription, DNase I hypersensitivity, and histone modifications. Tumor cfDNA shortening occurred simultaneously at both 5’ and 3’ ends of the DNA wrapped around nucleosomes. Conclusions: Tumor cfDNA shortening exhibited two distinctive modes. Tumor cfDNA purity and chromatin inaccessibility were contributing factors but insufficient to trigger a global transition from 166bp dominant to 134/144bp dominant phenotype.","abstract":"Background: Previous studies found that cell-free DNA (cfDNA) generated from tumors was shorter than that from healthy cells, and selecting short cfDNA could enrich for tumor cfDNA and improve its usage in early cancer diagnosis and treatment monitoring; however, the underlying mechanism of shortened tumor cfDNA was still unknown, which potentially limits its further clinical application.Results: Using targeted sequencing of cfDNA in a large cohort of solid tumor patient, sequencing reads harboring tumor-specific somatic mutations were isolated to examine the exact size distribution of tumor cfDNA. For the majority of studied cases, 166bp remained as the peak size of tumor cfDNA, with tumor cfDNA showing an increased proportion of short fragments (100-150bp). Less than 1% of cfDNA samples were found to be peaked at 134/144bp and independent of tumor cfDNA purity. Using whole-genome sequencing of cfDNA, we discovered a positive correlation between cfDNA shortening and the magnitude of chromatin inaccessibility, as measured by transcription, DNase I hypersensitivity, and histone modifications. Tumor cfDNA shortening occurred simultaneously at both 5’ and 3’ ends of the DNA wrapped around nucleosomes. Conclusions: Tumor cfDNA shortening exhibited two distinctive modes. Tumor cfDNA purity and chromatin inaccessibility were contributing factors but insufficient to trigger a global transition from 166bp dominant to 134/144bp dominant phenotype.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-07T16:23:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004136","title":"Phased whole genome sequencing of 10 melanoma samples","description":"We have sequenced 10 melanoma samples using 10X linked reads technology to obtain phased whole genome sequence data. Using this data, we created diploid personalized genomes for each sample and aligned functional genomics data obtained from the same samples in order to find allele specific events (such as allele-specific binding and allele-specific chromatin accessibility).","abstract":"We have sequenced 10 melanoma samples using 10X linked reads technology to obtain phased whole genome sequence data. Using this data, we created diploid personalized genomes for each sample and aligned functional genomics data obtained from the same samples in order to find allele specific events (such as allele-specific binding and allele-specific chromatin accessibility).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-07T20:14:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004137","title":"Developmental_Gonads","description":"Cell atlas of germinal cells and gonads\n\nSexual reproduction depends on the fusion of gametes (sperm and eggs) during fertilisation followed by implantation of the resulting embryo in the lining of the womb (the endometrium). Gametes halve their genome in preparation for fertilisation during a specialized cell division known as meiosis. The process by which meiosis is co-ordinated with gamete formation in females is poorly understood, principally because it commences in utero and is not completed until decades later when the mature egg is ovulated and fertilised. \nTo address the many gaps in our knowledge of the development of the germline and reproductive system in humans, we propose to generate a comprehensive cell atlas of the gonads fetal development and human germline. We will combine gene-expression profiling at the single-cell level and atac-seq with new methods of gene-expression detection directly on the tissue to study the cellular environment at an unprecedented resolution and coverage. Information about the expression of the myriad of cells and cell states in reproductive cells will greatly advance our understanding of the development of the female reproductive system and the emergence and maintenance of the female germline in humans. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Cell atlas of germinal cells and gonads\n\nSexual reproduction depends on the fusion of gametes (sperm and eggs) during fertilisation followed by implantation of the resulting embryo in the lining of the womb (the endometrium). Gametes halve their genome in preparation for fertilisation during a specialized cell division known as meiosis. The process by which meiosis is co-ordinated with gamete formation in females is poorly understood, principally because it commences in utero and is not completed until decades later when the mature egg is ovulated and fertilised. \nTo address the many gaps in our knowledge of the development of the germline and reproductive system in humans, we propose to generate a comprehensive cell atlas of the gonads fetal development and human germline. We will combine gene-expression profiling at the single-cell level and atac-seq with new methods of gene-expression detection directly on the tissue to study the cellular environment at an unprecedented resolution and coverage. Information about the expression of the myriad of cells and cell states in reproductive cells will greatly advance our understanding of the development of the female reproductive system and the emergence and maintenance of the female germline in humans. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004138","title":"HCA_Female_Reproductive_Adult_WSSS_RNA","description":"Female Reproductive cell Atlas\n \nThe Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Female Reproductive cell Atlas\n \nThe Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004139","title":"Amplicon based NGS of human CD4 and CD8 T cells","description":"Panel-based next-generation sequencing data of 211 human CD4 T cells, CD8 T cells and genomic DNA. The panel was designed to capture 260 SNVs in high linkage disequilibrium with multiple sclerosis susceptibility SNVs. NGS was carried out using PE300 reads on the Illumina MiSeq (Illumina Inc., San Diego, CA, United States).","abstract":"Panel-based next-generation sequencing data of 211 human CD4 T cells, CD8 T cells and genomic DNA. The panel was designed to capture 260 SNVs in high linkage disequilibrium with multiple sclerosis susceptibility SNVs. NGS was carried out using PE300 reads on the Illumina MiSeq (Illumina Inc., San Diego, CA, United States).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-08T10:44:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004140","title":"TCR sequencing on IBD","description":null,"abstract":"Growing evidence shows that inflammatory bowel disease (IBD) results from dysregulation of immune responses to gut microbes. T cell receptors (TCRs) expressed on the T cell surface plays critical roles in discriminating pathogens from commensal intestinal microorganisms at the front line of the adaptive immune system. The breakdown of this interaction may trigger persistent inflammatory responses to gut bacteria, resulting in IBD. Taking advantage of high-throughput sequencing, we developed an integrated approach to dissect the intestinal TCR repertoires underlying IBD by collecting peripheral blood and inflamed intestine from the same set of 11 IBD cases. The intestinal TCR repertoires show lower clonotype diversity (p&lt;0.05) and stronger clonal expansion (p&lt;0.02) than those in the blood. This pattern becomes more profound in TCRs unique to the inflamed tissue compared with shared TCRs. Our approach further identified the increased usage of TRAV12-3 (false discovery rate, FDR&lt;5%), which biases its choices of J genes towards the reduction of TRAJ37 and TRAJ43 usage (FDR&lt;20%) in the inflamed intestine. Our genomic profiling suggests that this selective bias of V and J gene usage may lead to a loss of diversity in the intestinal TCR repertoires and result in mucosal inflammation in IBD.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004141","title":"HG_Genome_wide_CRISPR_Screens_in_primary_T_cells_","description":"Human T cells will be transduced with a lentiviral pool library and Cas9 will be delivered by electroporation.  Edited cells will be re-stimulated with anti-CD3 and anti-CD28, exposed to anti-TNF-alpha and sorted into relevant phenotypes, for example non-proliferating or highly proliferating  populations. Genomic DNA will be isolated, sgRNA amplified and barcoded for sequencing.\n\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Anti TNF-α antibodies, such as infliximab (IFX) and adalimumab (ADA), are effective biological therapies used to treat several immune mediated diseases, including inflammatory bowel disease. However,  despite great efficacy in many patients, at least one third do not respond adequately. Therefore, a better understanding of the events that lead to resistance to anti-TNF therapies could lead to refined treatment regimens and may also highlight mechanisms to prevent patients' resistance to these therapies.\nIn this study we aim to investigate how T cells acquire resistance to anti-TNF-induced suppression. To do so, we will perform genome wide CRISPR screenings in primary T cells from healthy blood donors and expose these cells to the comercially avaiable anti-TNF drug, infliximab. Genomic DNA will be isolated from higly proliferative populations. To identify hits upon cell exposure to the drug, we will useMAGeCK algorithm followed by FluteMLE MAGeFluteMLE r downstream GO term and KEGG pathway enrichment analysis. sgRNA with strong enrichment scores in the will be validate by functional experiments. These experiments will highlight genes that are important in the response of T cells to drugs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004142","title":"DIMID study: Fecal microbiota transplantation (FMT) in new-onset type 1 diabetes humans","description":"Recent-onset (&lt;6 weeks) T1D patients were randomized in two groups to receive three autologous or allogenic (healthy donor) FMTs over a period of 6 months after diagnosis. Our primary outcome parameter was stimulated insulin release evaluated by mixed-meal tests during 1 year follow-up. Secondary outcome parameters were changes in glycemic control, fasting plasma metabolites, T cell autoimmunity, small intestinal gene expression profile and intestinal microbiota composition by 16S rRNA gene and metagenome sequence analysis.","abstract":"Recent-onset (&lt;6 weeks) T1D patients were randomized in two groups to receive three autologous or allogenic (healthy donor) FMTs over a period of 6 months after diagnosis. Our primary outcome parameter was stimulated insulin release evaluated by mixed-meal tests during 1 year follow-up. Secondary outcome parameters were changes in glycemic control, fasting plasma metabolites, T cell autoimmunity, small intestinal gene expression profile and intestinal microbiota composition by 16S rRNA gene and metagenome sequence analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004143","title":"HCA_Brain_Disease_Downs_Bayraktar_RNA","description":"Single-nucleus sequencing of Down syndrome (trisomy 21) and control fetal brain samples.\n\nIn this study, we apply single-nucleus sequencing to Down syndrome (trisomy 21) and control fetal brain samples from a range of cortical brain regions and time-points during mid-gestation (post-conception weeks 12 to 19). We aim to understand how and which cell types, cortical regions and neural circuits are affected in Down syndrome and how this could relate to the specific cognitive symptoms and high prevalence of dementia in patients. We furthermore envisage that studying fetal brain development in the presence of this selective gene dosage increase, will offer new insights into fundamental neurodevelopmental processes, including neural stem cell or progenitor proliferation/differentiation, interneuron differentiation/migration, oligodendrocyte development and cell-cell communication in the cortical ventricular zone.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Single-nucleus sequencing of Down syndrome (trisomy 21) and control fetal brain samples.\n\nIn this study, we apply single-nucleus sequencing to Down syndrome (trisomy 21) and control fetal brain samples from a range of cortical brain regions and time-points during mid-gestation (post-conception weeks 12 to 19). We aim to understand how and which cell types, cortical regions and neural circuits are affected in Down syndrome and how this could relate to the specific cognitive symptoms and high prevalence of dementia in patients. We furthermore envisage that studying fetal brain development in the presence of this selective gene dosage increase, will offer new insights into fundamental neurodevelopmental processes, including neural stem cell or progenitor proliferation/differentiation, interneuron differentiation/migration, oligodendrocyte development and cell-cell communication in the cortical ventricular zone.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004144","title":"Myeloproliferative_neoplasms_MAJIC_TGS","description":"Targeted sequencing of haematopoietic colonies.","abstract":"Cancer clones emerge and evolve through somatic mutation acquisition and Darwinian selection, but the dynamics of clonal evolution remain poorly understood and predicting disease progression remains a real challenge. Genes that regulate the epigenome are clearly important targets of mutations in cancer, but the mechanisms by which they drive tumour evolution remain unknown.\nThe myeloproliferative neoplasms (MPN) are haematopoietic disorders that represent an excellent model to study genomic and epigenomic evolution in human cancers: (i) They are genetically well-defined with disease driving mutations in JAK2, CALR (which I described in 2013) or MPL, present alongside mutations in epigenetic regulators, such as, DNMT3A. (ii) Disease can be either stable, or progress to leukaemia or myelofibrosis, providing the opportunity to study the basis for these evolutionary differences, and (iii) Primary cells can be serially sampled at the clonal level enabling inter- and intra-clonal studies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004145","title":"Pseudodiastrophic dysplasia expands the known phenotypic spectrum of defects in proteoglycan biosynthesis","description":"Pseudodiastrophic dysplasia (PDD) is a severe skeletal dysplasia associated with prenatal manifestation and early lethality. Clinically, PDD is classified as a ‘dysplasia with multiple joint dislocations’ however, the molecular aetiology of the disorder is currently unknown. In order to identify the genetic defects underlying PDD, we performed whole exome sequencing (WES) on 3 patients from 2 unrelated families, clinically diagnosed with PDD. WES resulted in the identification of bi-allelic variants in the established skeletal dysplasia genes, B3GAT3 (Family 1) and CANT1 (Family 2). Mutations in these genes have previously been reported to cause ‘multiple joint dislocations, short stature, and craniofacial dysmorphism with or without congenital heart defects’ (B3GAT3) and Desbuquois dysplasia 1 (CANT1); disorders in the same nosological group as PDD. Follow-up of the B3GAT3 variants demonstrated significantly reduced B3GAT3/GlcAT-I expression. Downstream in vitro functional analysis revealed abolished biosynthesis of glycosaminoglycan side chains on proteoglycans. Functional evaluation of the CANT1 variant showed impaired nucleotidase activity, which results in inhibition of glycosaminoglycan synthesis through accumulation of uridine diphosphate. For the families described in this study, the PDD phenotype was caused by mutations in the known skeletal dysplasia genes B3GAT3 and CANT1, demonstrating the advantage of genomic analyses in delineating the molecular diagnosis of skeletal dysplasias. This finding expands the phenotypic spectrum of B3GAT3- and CANT1- related skeletal dysplasias to include PDD, and highlights the significant phenotypic overlap of conditions within the proteoglycan biosynthesis pathway.","abstract":"Pseudodiastrophic dysplasia (PDD) is a severe skeletal dysplasia associated with prenatal manifestation and early lethality. Clinically, PDD is classified as a ‘dysplasia with multiple joint dislocations’ however, the molecular aetiology of the disorder is currently unknown. In order to identify the genetic defects underlying PDD, we performed whole exome sequencing (WES) on 3 patients from 2 unrelated families, clinically diagnosed with PDD. WES resulted in the identification of bi-allelic variants in the established skeletal dysplasia genes, B3GAT3 (Family 1) and CANT1 (Family 2). Mutations in these genes have previously been reported to cause ‘multiple joint dislocations, short stature, and craniofacial dysmorphism with or without congenital heart defects’ (B3GAT3) and Desbuquois dysplasia 1 (CANT1); disorders in the same nosological group as PDD. Follow-up of the B3GAT3 variants demonstrated significantly reduced B3GAT3/GlcAT-I expression. Downstream in vitro functional analysis revealed abolished biosynthesis of glycosaminoglycan side chains on proteoglycans. Functional evaluation of the CANT1 variant showed impaired nucleotidase activity, which results in inhibition of glycosaminoglycan synthesis through accumulation of uridine diphosphate. For the families described in this study, the PDD phenotype was caused by mutations in the known skeletal dysplasia genes B3GAT3 and CANT1, demonstrating the advantage of genomic analyses in delineating the molecular diagnosis of skeletal dysplasias. This finding expands the phenotypic spectrum of B3GAT3- and CANT1- related skeletal dysplasias to include PDD, and highlights the significant phenotypic overlap of conditions within the proteoglycan biosynthesis pathway.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-09T23:29:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004146","title":"HSC_population_dynamics___PX001_samples","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-10T13:25:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004147","title":"Chracterising_cellur_pathways_underlying_CD3_CD28_activation_of_human_CD4__cells","description":"We devised an approach to disentangle the TCR and CD28 pathways upon stimulation in naive and memory primary human CD4+ T cells (Tcons) in response to defined stimulatory signals. Sorted Tcons were activated using a titration of anti-CD3 and anti-CD28 in combination as well as individually. As a control we cultured cells in the same conditions but without the stimuli. In total, we defined seven conditions from four individuals for sequencing.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Two signals are necessary for a successful T cell activation; interaction of the T cell receptor (TCR) with the major histocompatibility complex II (MHC) antigens on the antigen presenting cells (APC) and interaction of the CD28 receptor on the lymphocyte with B7 proteins presented by the APC.  The role of CD28 receptor in T cell activation remains poorly understood, with an ongoing debate on whether it amplifies TCR based signal, drives unique changes in the cell or whether it is neede at all for certain T cell subsets activation. Self-recognition by TCR can lead to autoimmunity, highlighting the importance to better study these pathways using genomics tools.\nWe aimed to decouple the T cell activation signals in order to better understand their role in immune response. I believe that by joining immunophenotyping with gene expression studies we can elucidate the pathways engaged by CD28 co-stimulation for a successful T cell activation in naive and memory cells. That will also allow us to explore the effect of increasing TCR signal in the differentiation of naive cells. Looking at gene expression variability between individuals, as well as their threshold response to a stimulus, we can gain an insight into the role of genetic variants in activation processes of CD4+ cells.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-10T13:19:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004148","title":"geneseeq 20200110 test","description":"geneseeq 20200110 test","abstract":"geneseeq 20200110 test","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004149","title":"Development_Disorders_in_Africa","description":"Developmental disorders (DD) are severe, chronic disabilities, and are systematically increasing in prevalence in low-and middle-income countries (LMIC). Genetic causes are known to be a prominent contributor to the aetiology of DD, but current diagnostic tests have a low success yield. Whole-exome sequencing (WES) can add significant precision to the diagnosis of DD, and can directly affect care, whilst overall costing less than the cascade of conventional genetic testing typically required to elucidate the genetic cause of DD.","abstract":"Developmental disorders (DD) are severe, chronic disabilities, and are systematically increasing in prevalence in low-and middle-income countries (LMIC). Genetic causes are known to be a prominent contributor to the aetiology of DD, but current diagnostic tests have a low success yield. Whole-exome sequencing (WES) can add significant precision to the diagnosis of DD, and can directly affect care, whilst overall costing less than the cascade of conventional genetic testing typically required to elucidate the genetic cause of DD.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004150","title":"scRNA_seq_of_circulatory_immune_cells_from_Crohn_s_disease_patient_blood","description":"Whole blood from Crohn's disease patients with active inflammation in the terminal ileum was depleted of red blood cells and partially depleted of granulocytes before single cell sequencing using 10X genomics 3'v3 kit followed by Illumina sequencing (HS4000 and NovaSeq)\n \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Whole blood from Crohn's disease patients with active inflammation in the terminal ileum was depleted of red blood cells and partially depleted of granulocytes before single cell sequencing using 10X genomics 3'v3 kit followed by Illumina sequencing (HS4000 and NovaSeq)","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-10T15:26:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004151","title":"Cancer immune control needs senescence induction by Stat1 dependent cell cycle regulator pathways in tumours","description":"Immune checkpoint bloackade (ICB)-based or natural cancer immune responses largely eliminate tumours. Yet, they require additional mechanisms to arrest those cancer cells that are not rejected. Cytokine-induced senescence (CIS) can stably arrest cancer cells, suggesting that interferon-dependent induction of senescence-inducing cell cycle regulators is needed to control those cancer cells that escape from killing. Here we report in two different cancers sensitive to T cell-mediated rejection, we show that deletion of the senescence-inducing cell cycle regulators p16Ink4a/p19Arf (Cdkn2a) or p21Cip1 (Cdkn1a)  in the tumour cells abrogated both, the natural and the ICB-induced cancer immune control. Also in humans, melanoma metastases that progressed rapidly during ICB have losses of senescence-inducing genes and amplifications of senescence inhibitors. Metastatic cells also resist CIS. Such genetic and functional alterations are infrequent in metastatic melanomas regressing during ICB. Thus, activation of tumour-intrinsic, senescence-inducing cell cycle regulators is required to stably arrest those cancer cells that escape from eradication.","abstract":"Immune checkpoint bloackade (ICB)-based or natural cancer immune responses largely eliminate tumours. Yet, they require additional mechanisms to arrest those cancer cells that are not rejected. Cytokine-induced senescence (CIS) can stably arrest cancer cells, suggesting that interferon-dependent induction of senescence-inducing cell cycle regulators is needed to control those cancer cells that escape from killing. Here we report in two different cancers sensitive to T cell-mediated rejection, we show that deletion of the senescence-inducing cell cycle regulators p16Ink4a/p19Arf (Cdkn2a) or p21Cip1 (Cdkn1a)  in the tumour cells abrogated both, the natural and the ICB-induced cancer immune control. Also in humans, melanoma metastases that progressed rapidly during ICB have losses of senescence-inducing genes and amplifications of senescence inhibitors. Metastatic cells also resist CIS. Such genetic and functional alterations are infrequent in metastatic melanomas regressing during ICB. Thus, activation of tumour-intrinsic, senescence-inducing cell cycle regulators is required to stably arrest those cancer cells that escape from eradication.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-10T16:51:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004152","title":"Transcriptomic signatures of CD4+ T cells from visceral leishmaniasis (VL) patients","description":"Bulk RNA-sequencing was performed on CD4+ T cells isolated from the blood of visceral leishmaniasis patients (n = 12) and endemic controls (EC; n = 12). CD4+ T cells were obtained by magnetic-activated cell sorting (MACS). Alterations in the transcripts of T helper (Th) cells during infection were identified.","abstract":"Bulk RNA-sequencing was performed on CD4+ T cells isolated from the blood of visceral leishmaniasis patients (n = 12) and endemic controls (EC; n = 12). CD4+ T cells were obtained by magnetic-activated cell sorting (MACS). Alterations in the transcripts of T helper (Th) cells during infection were identified.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-13T04:37:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004153","title":"The miR-185/PAK6 Axis Predicts Therapy Response and Regulates Survival of Drug-Resistant Leukemic Stem Cells in Chronic Myeloid Leukemia","description":"Overcoming drug resistance and targeting cancer stem cells remain challenges for curative cancer treatment. To investigate the role of miRNAs in regulating drug resistance and leukemic stem cell (LSCs) fate, we performed global transcriptome profiling in treatment-naïve chronic myeloid leukemia (CML) stem/progenitor cells and identified that miR-185 levels anticipate their response to ABL tyrosine kinase inhibitors (TKIs). miR-185 functions as a tumor suppressor; its restored expression impaired survival of drug-resistant cells, sensitized them to TKIs in vitro, and markedly eliminated long-term repopulating LSCs and infiltrating blast cells, conferring a survival advantage in pre-clinical xenotransplantation models. Integrative analysis with mRNA profiles uncovered PAK6 as a crucial target of miR-185 and pharmacological inhibition of PAK6 perturbed the RAS/MAPK pathway and mitochondrial activity, sensitizing therapy-resistant cells to TKIs. Thus, miR-185 presents as a potential predictive biomarker, and dual targeting of miR-185-mediated PAK6 activity and BCR-ABL may provide a valuable strategy for overcoming drug resistance in patients.","abstract":"Overcoming drug resistance and targeting cancer stem cells remain challenges for curative cancer treatment. To investigate the role of miRNAs in regulating drug resistance and leukemic stem cell (LSCs) fate, we performed global transcriptome profiling in treatment-naïve chronic myeloid leukemia (CML) stem/progenitor cells and identified that miR-185 levels anticipate their response to ABL tyrosine kinase inhibitors (TKIs). miR-185 functions as a tumor suppressor; its restored expression impaired survival of drug-resistant cells, sensitized them to TKIs in vitro, and markedly eliminated long-term repopulating LSCs and infiltrating blast cells, conferring a survival advantage in pre-clinical xenotransplantation models. Integrative analysis with mRNA profiles uncovered PAK6 as a crucial target of miR-185 and pharmacological inhibition of PAK6 perturbed the RAS/MAPK pathway and mitochondrial activity, sensitizing therapy-resistant cells to TKIs. Thus, miR-185 presents as a potential predictive biomarker, and dual targeting of miR-185-mediated PAK6 activity and BCR-ABL may provide a valuable strategy for overcoming drug resistance in patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-13T16:50:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004154","title":"Targeted de novo phasing and assembly by template mutagenesis","description":null,"abstract":"We present a protocol and informatics to obtain ultra-low-error-rate de novo haplotype-phased sequence assemblies of regions up to 5 KB in length without reliance on a reference genome and using conventional short-read sequencing. We accomplish this by imprinting each template strand from the designated region with a dense and unique mutational pattern by partial bisulfite conversion. This process randomly and independently converts ~50% of cytosines to uracils. Short read sequencing libraries are made from the mutated templates as well as from unmutated templates. A conservative De Bruijn graph approach seeds an assembly of the mutated templates, which we then extend and join by paired-end read mapping. Using the unmutated sequence library, we ‘correct’ the mutated bases. We then partition each corrected template assembly into one of two or more haplotypes. Finally, we take a consensus over each haplotype, correcting any unresolved mutations and PCR errors, obtaining per-base-error rates of ~10-9. We apply this method to a four-member nuclear family, correctly assembling and phasing two genomic intervals, including the highly polymorphic HLA-B gene.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004155","title":"Molecular profiling of human non-small cell lung cancer by single-cell RNA-seq","description":"Lung cancer is a leading cause of cancer-related death worldwide is the one of the malignant tumors with the highest morbidity and mortality worldwide. To comprehensively analyze the molecular heterogeneity of non-small cell lung cancer (NSCLC), we performed single-cell RNA-seq analyses for 7,364 individual cells of tumor tissues and matched  normal tissues from 19 primary lung cancer patients as well as 1 pulmonary chondroid hamartoma patient. In six of these patients, we identified a significant proportion of cancer cells simultaneously express classical marker genes for two or even three \thistologic subtypes different types of of lung cancerNSCLC  - adenocarcinoma (ADC), squamous cell carcinoma (SCC), and large cell neuroendocrine carcinoma (LCNEC), which was verified by co-immunostaining and RNA FISH. This indicates that these mixed-lineage tumor cells are highly plastic with mixed features of different types of NSCLC. Both of the CNV patterns and mitochondrial mutations  clearly showed that the mixed-lineage and single-lineage tumor cells in the same patient had common tumor ancestors rather than independent different origins. Based on the pseudotime trajectory of gene expression dynamics from normal epithelial cells to cancer cells, we identified a set ofa cancer specific gene set has been identifiedcancer specifically expressed genes, including AKR1B1 and RAMP1. Knockdown experiments verified that AKR1B1 and RAMP1 were necessary for tumor growth, suggesting that they can serve as candidate targets for tumor therapy. In summary, our work provides novel insights into the heterogeneity of NSCLC and offers clues for their subtype classification, diagnosis and treatment.","abstract":"Lung cancer is a leading cause of cancer-related death worldwide is the one of the malignant tumors with the highest morbidity and mortality worldwide. To comprehensively analyze the molecular heterogeneity of non-small cell lung cancer (NSCLC), we performed single-cell RNA-seq analyses for 7,364 individual cells of tumor tissues and matched  normal tissues from 19 primary lung cancer patients as well as 1 pulmonary chondroid hamartoma patient. In six of these patients, we identified a significant proportion of cancer cells simultaneously express classical marker genes for two or even three \thistologic subtypes different types of of lung cancerNSCLC  - adenocarcinoma (ADC), squamous cell carcinoma (SCC), and large cell neuroendocrine carcinoma (LCNEC), which was verified by co-immunostaining and RNA FISH. This indicates that these mixed-lineage tumor cells are highly plastic with mixed features of different types of NSCLC. Both of the CNV patterns and mitochondrial mutations  clearly showed that the mixed-lineage and single-lineage tumor cells in the same patient had common tumor ancestors rather than independent different origins. Based on the pseudotime trajectory of gene expression dynamics from normal epithelial cells to cancer cells, we identified a set ofa cancer specific gene set has been identifiedcancer specifically expressed genes, including AKR1B1 and RAMP1. Knockdown experiments verified that AKR1B1 and RAMP1 were necessary for tumor growth, suggesting that they can serve as candidate targets for tumor therapy. In summary, our work provides novel insights into the heterogeneity of NSCLC and offers clues for their subtype classification, diagnosis and treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004156","title":"FAM50A_Disruption_in_TOV21G_Cells___RNAseq","description":"In this project we aimed to assess the transcriptional consequences of disrupting FAM50A in TOV21G cells in vivo. To do this we generated a dox inducible FAM50A gRNA allele such that we could conditionally inactivate FAM50A by feeding mice a diet containing doxycycline. Tumour masses were harvested from mice when they reached the ethical limit and RNA was extracted for RNA-Seq analysis.","abstract":"In this project we aimed to assess the transcriptional consequences of disrupting FAM50A in TOV21G cells in vivo. To do this we generated a dox inducible FAM50A gRNA allele such that we could conditionally inactivate FAM50A by feeding mice a diet containing doxycycline. Tumour masses were harvested from mice when they reached the ethical limit and RNA was extracted for RNA-Seq analysis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-15T14:34:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004157","title":"Metastatic Adult Pancreatoblastoma: Multimodal Treatment and Molecular Characterization of a Very Rare Disease (NCT MASTER)","description":"Pancreatoblastoma is a rare malignant tumor that occurs predominantly in children. We identified four adult patients with metastasizing pancreatoblastoma at a high-volume German university cancer center which were treated with multimodal therapies between 2013 and 2018. In three cases, we performed a comprehensive molecular analysis that included whole-genome sequencing (WGS) or whole-exome sequencing (WES); transcriptome sequencing was performed in two cases, respectively. Subsequent recommendations of molecularly stratified treatment options were discussed within a dedicated molecular tumor board (MTB) embedded in a precision oncology program (NCT MASTER).","abstract":"Pancreatoblastoma is a rare malignant tumor that occurs predominantly in children. We identified four adult patients with metastasizing pancreatoblastoma at a high-volume German university cancer center which were treated with multimodal therapies between 2013 and 2018. In three cases, we performed a comprehensive molecular analysis that included whole-genome sequencing (WGS) or whole-exome sequencing (WES); transcriptome sequencing was performed in two cases, respectively. Subsequent recommendations of molecularly stratified treatment options were discussed within a dedicated molecular tumor board (MTB) embedded in a precision oncology program (NCT MASTER).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-15T14:55:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004158","title":"Molecular determinants for sensitivity to pazopanib in leiomyosarcoma, synovial sarcoma, and angiosarcoma.","description":"Pazopanib is a tyrosine kinase inhibitor with highest activity against VEGFR1 (FLT1) and VEGFR2 (KDR) along with other targets including VEGFR3, PDGFRa, PDGFRb, cKIT, FGFR1, FGFR3, FGFR4, FAK, ABL1, JNK1, Tie-2, Met, IGF1R, and EGFR (Lee, Jones, and Huang Signal Transduct Target Ther 2019; 4:16). Its initial activity in soft tissue sarcoma (STS) was described by Sleijfer et al. (2009) where a high proportion of leiomyosarcoma (LMS) (44%) and synovial sarcoma (49%) patients remained without progression at 12 weeks. Based on these findings, a multi-institutional randomized placebo controlled phase III trial was conducted (PALLETTE trial) to investigate the activity of pazopanib in the treatment of sarcomas excluding liposarcomas (van der Graaf WT et al. Lancet 2012; 379:1879). There, a large proportion of the patients tested were of LMS histology (42; 29%) and the overall median progression free survival (PFS) was 4.6 months for the treatment as compared to 1.6 months in the placebo arm. There was no survival advantage in the pazopanib arm. Partial response rate was as low as 6% and stable disease occurred in 67% patients compared to 38% in the placebo arm. Progressive disease was observed in 23% of patients receiving pazopanib. Based on this study, pazopanib is currently approved for the treatment of advanced non-adipogenic STS patients for which standard chemotherapy has failed. Here, we conducted whole exome and transcriptome profiling of leiomyosarcoma (N = 33), synovial sarcoma (N = 25), and angiosarcoma (N = 9) patients who were given pazopanib. To date, we have collected all available pretreatment and post-treatment samples from 67 patients (Table 1) (treated from 2012 to 2017), 4 frozen and the remainder FFPE.","abstract":"Pazopanib is a tyrosine kinase inhibitor with highest activity against VEGFR1 (FLT1) and VEGFR2 (KDR) along with other targets including VEGFR3, PDGFRa, PDGFRb, cKIT, FGFR1, FGFR3, FGFR4, FAK, ABL1, JNK1, Tie-2, Met, IGF1R, and EGFR (Lee, Jones, and Huang Signal Transduct Target Ther 2019; 4:16). Its initial activity in soft tissue sarcoma (STS) was described by Sleijfer et al. (2009) where a high proportion of leiomyosarcoma (LMS) (44%) and synovial sarcoma (49%) patients remained without progression at 12 weeks. Based on these findings, a multi-institutional randomized placebo controlled phase III trial was conducted (PALLETTE trial) to investigate the activity of pazopanib in the treatment of sarcomas excluding liposarcomas (van der Graaf WT et al. Lancet 2012; 379:1879). There, a large proportion of the patients tested were of LMS histology (42; 29%) and the overall median progression free survival (PFS) was 4.6 months for the treatment as compared to 1.6 months in the placebo arm. There was no survival advantage in the pazopanib arm. Partial response rate was as low as 6% and stable disease occurred in 67% patients compared to 38% in the placebo arm. Progressive disease was observed in 23% of patients receiving pazopanib. Based on this study, pazopanib is currently approved for the treatment of advanced non-adipogenic STS patients for which standard chemotherapy has failed. Here, we conducted whole exome and transcriptome profiling of leiomyosarcoma (N = 33), synovial sarcoma (N = 25), and angiosarcoma (N = 9) patients who were given pazopanib. To date, we have collected all available pretreatment and post-treatment samples from 67 patients (Table 1) (treated from 2012 to 2017), 4 frozen and the remainder FFPE.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004159","title":"Genomic analysis of prostate cancer","description":null,"abstract":"Genomic analysis of prostate cancer samples for single nucleotide and structural variants","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004160","title":"Neoadjuvant immunotherapy leads to pathological responses in MMR proficient and MMR deficient early stage colon cancers","description":"PD-1 plus CTLA-4 blockade is highly effective in advanced-stage, mismatch repair (MMR)-deficient (dMMR) colorectal cancers, yet not in MMR-proficient (pMMR) tumors. We postulated a higher efficacy of neoadjuvant immunotherapy in early-stage colon cancers. In the exploratory NICHE study (ClinicalTrials.gov: NCT03026140), patients with dMMR or pMMR tumors received a single dose of ipilimumab and two doses of nivolumab before surgery, the pMMR group with or without celecoxib. The primary objective was safety and feasibility; 40 patients with 21 dMMR and 20 pMMR tumors were treated, and 3 patients received nivolumab monotherapy in the safety run-in. Treatment was well tolerated and all patients underwent radical resections without delays, meeting the primary endpoint. Of the patients who received ipilimumab + nivolumab (20 dMMR and 15 pMMR tumors), 35 were evaluable for efficacy and translational endpoints. Pathological response was observed in 20/20 (100%; 95% exact confidence interval (CI): 86–100%) dMMR tumors, with 19 major pathological responses (MPRs, ≤10% residual viable tumor) and 12 pathological complete responses. In pMMR tumors, 4/15 (27%; 95% exact CI: 8–55%) showed pathological responses, with 3 MPRs and 1 partial response. CD8+PD-1+ T cell infiltration was predictive of response in pMMR tumors. These data indicate that neoadjuvant immunotherapy may have the potential to become the standard of care for a defined group of colon cancer patients when validated in larger studies with at least 3 years of disease-free survival data.","abstract":"PD-1 plus CTLA-4 blockade is highly effective in advanced-stage, mismatch repair (MMR)-deficient (dMMR) colorectal cancers, yet not in MMR-proficient (pMMR) tumors. We postulated a higher efficacy of neoadjuvant immunotherapy in early-stage colon cancers. In the exploratory NICHE study (ClinicalTrials.gov: NCT03026140), patients with dMMR or pMMR tumors received a single dose of ipilimumab and two doses of nivolumab before surgery, the pMMR group with or without celecoxib. The primary objective was safety and feasibility; 40 patients with 21 dMMR and 20 pMMR tumors were treated, and 3 patients received nivolumab monotherapy in the safety run-in. Treatment was well tolerated and all patients underwent radical resections without delays, meeting the primary endpoint. Of the patients who received ipilimumab + nivolumab (20 dMMR and 15 pMMR tumors), 35 were evaluable for efficacy and translational endpoints. Pathological response was observed in 20/20 (100%; 95% exact confidence interval (CI): 86–100%) dMMR tumors, with 19 major pathological responses (MPRs, ≤10% residual viable tumor) and 12 pathological complete responses. In pMMR tumors, 4/15 (27%; 95% exact CI: 8–55%) showed pathological responses, with 3 MPRs and 1 partial response. CD8+PD-1+ T cell infiltration was predictive of response in pMMR tumors. These data indicate that neoadjuvant immunotherapy may have the potential to become the standard of care for a defined group of colon cancer patients when validated in larger studies with at least 3 years of disease-free survival data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-17T18:27:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004161","title":"Whole genome, targeted and RNA sequencing in Korean cholangiocarcinomas","description":null,"abstract":"Despite the epidemiological association between intrahepatic cholangiocarcinoma (iCCA) and hepatitis B virus (HBV) infection, little is known about the relevant oncogenic mechanisms. We profiled a cohort of 108 HBV-infected iCCAs using whole-genome sequencing, RNA sequencing, and targeted capture sequencing, and found that HBV had inserted at multiple sites in the iCCA genomes in 49 (45.4%) of the tumors. Recurrent viral integration breakpoints were found at 10 different sites. The most common insertional hotspot (7 tumors) was in the TERT promoter region, where insertion was accompanied by promoter hyperactivity. A distinctive intergenic insertion, between DMRTA1 and LINC01239 (chr9p21.3), had oncogenic effects through activation of the mTOR/4EBP/S6K pathway. Many of the driver gene mutations in the HBV-related iCCAs involved drivers of either 167 HBV-related hepatocellular carcinomas (ARID1A and RB1) or 154 conventional iCCAs (KRAS, IDH1, SMAD4, and PIK3CA). Our findings provide insight into the behavior of iCCAs driven by various pathological mechanisms involving HBV integration events and associated genomic aberrations. This knowledge should be of use in managing HBV carriers.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004162","title":"whole genome sequencing in cholangiocarcinomas","description":null,"abstract":"Despite the epidemiological association between intrahepatic cholangiocarcinoma (iCCA) and hepatitis B virus (HBV) infection, little is known about the relevant oncogenic mechanisms. We profiled a cohort of 108 HBV-infected iCCAs using whole-genome sequencing, RNA sequencing, and targeted capture sequencing, and found that HBV had inserted at multiple sites in the iCCA genomes in 49 (45.4%) of the tumors. Recurrent viral integration breakpoints were found at 10 different sites. The most common insertional hotspot (7 tumors) was in the TERT promoter region, where insertion was accompanied by promoter hyperactivity. A distinctive intergenic insertion, between DMRTA1 and LINC01239 (chr9p21.3), had oncogenic effects through activation of the mTOR/4EBP/S6K pathway. Many of the driver gene mutations in the HBV-related iCCAs involved drivers of either 167 HBV-related hepatocellular carcinomas (ARID1A and RB1) or 154 conventional iCCAs (KRAS, IDH1, SMAD4, and PIK3CA). Our findings provide insight into the behavior of iCCAs driven by various pathological mechanisms involving HBV integration events and associated genomic aberrations. This knowledge should be of use in managing HBV carriers.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004163","title":"targeted sequencing in cholangiocarcinomas","description":null,"abstract":"Despite the epidemiological association between intrahepatic cholangiocarcinoma (iCCA) and hepatitis B virus (HBV) infection, little is known about the relevant oncogenic mechanisms. We profiled a cohort of 108 HBV-infected iCCAs using whole-genome sequencing, RNA sequencing, and targeted capture sequencing, and found that HBV had inserted at multiple sites in the iCCA genomes in 49 (45.4%) of the tumors. Recurrent viral integration breakpoints were found at 10 different sites. The most common insertional hotspot (7 tumors) was in the TERT promoter region, where insertion was accompanied by promoter hyperactivity. A distinctive intergenic insertion, between DMRTA1 and LINC01239 (chr9p21.3), had oncogenic effects through activation of the mTOR/4EBP/S6K pathway. Many of the driver gene mutations in the HBV-related iCCAs involved drivers of either 167 HBV-related hepatocellular carcinomas (ARID1A and RB1) or 154 conventional iCCAs (KRAS, IDH1, SMAD4, and PIK3CA). Our findings provide insight into the behavior of iCCAs driven by various pathological mechanisms involving HBV integration events and associated genomic aberrations. This knowledge should be of use in managing HBV carriers.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004164","title":"RNA-seq in cholangiocarcinomas","description":null,"abstract":"Despite the epidemiological association between intrahepatic cholangiocarcinoma (iCCA) and hepatitis B virus (HBV) infection, little is known about the relevant oncogenic mechanisms. We profiled a cohort of 108 HBV-infected iCCAs using whole-genome sequencing, RNA sequencing, and targeted capture sequencing, and found that HBV had inserted at multiple sites in the iCCA genomes in 49 (45.4%) of the tumors. Recurrent viral integration breakpoints were found at 10 different sites. The most common insertional hotspot (7 tumors) was in the TERT promoter region, where insertion was accompanied by promoter hyperactivity. A distinctive intergenic insertion, between DMRTA1 and LINC01239 (chr9p21.3), had oncogenic effects through activation of the mTOR/4EBP/S6K pathway. Many of the driver gene mutations in the HBV-related iCCAs involved drivers of either 167 HBV-related hepatocellular carcinomas (ARID1A and RB1) or 154 conventional iCCAs (KRAS, IDH1, SMAD4, and PIK3CA). Our findings provide insight into the behavior of iCCAs driven by various pathological mechanisms involving HBV integration events and associated genomic aberrations. This knowledge should be of use in managing HBV carriers.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004165","title":"Genomic and epigenomic insights into the origin, pathogenesis and clinical behavior of mantle cell lymphoma subtypes","description":"Mantle Cell Lymphoma can be subdivided into conventional (cMCL) and leukemic non-nodal MCL (nnMCL), which differ in the cell of origin, gene expression, biological characteristics and clinical evolution. Using genomic, epigenomic and transcriptomic data we identified common and particular alterations in the two subtypes, either point mutations, copy number alterations or structural variants some of them with prognostic impact.","abstract":"Mantle Cell Lymphoma can be subdivided into conventional (cMCL) and leukemic non-nodal MCL (nnMCL), which differ in the cell of origin, gene expression, biological characteristics and clinical evolution. Using genomic, epigenomic and transcriptomic data we identified common and particular alterations in the two subtypes, either point mutations, copy number alterations or structural variants some of them with prognostic impact.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-19T18:52:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004166","title":"Sequencing_of_Multiplexed_gRNA_Library","description":"This study will deep sequence 24 test samples that have been prepared using different protocols, aimed to optimise library preparation. The samples were prepared by PCR from genomic DNA using different amounts/volumes. We employed in the screens a minimised library encoding two gRNA expression cassettes (aka 5' and 3' cassette), therefore the study will generate two libraries per sample.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Gene knock-out phenotypes are known to vary across yeast strains and cancer cell lines. Human genes do not function the same way in different individuals. The extent to which gene essentiality and other cellular traits change between human individuals and the genetic determinants that suppress or enhance the deleterious effects of a mutation remain unknown. Here, we propose to measure the variation of human gene essentiality across different healthy donors using genome-wide CRISPR/Cas9 screens. We generated multiple Cas9-expressing monoclonal lines with high Cas9 activity for more than 40 induced pluripotent stem cell (iPSC) lines derived from different individuals. We have performed duplicate genome-wide dropout screens in these lines. CRISPR libraries were made from the CRISPR screens cell pellets and deep sequenced with illumina sequencing. The contributions of donor genotype, clonality of isogenic iPSC lines, experimental noise and other determinants to variation in gene essentiality will be validated and quantified. We expect variability in gene essentiality scores across different donors and this work will improve our understanding of how each gene impacts cellular growth and survival, and of gene essentiality in different genetic backgrounds.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004167","title":"HSC_population_dynamics__bulk_RNA_seq___CB002","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004168","title":"High-resolution analyses of human sperm dynamic methylome reveals thousands of novel age-related epigenetic alterations","description":"Age-dependent modifications of the germ cells epigenome remain poorly understood. Our objective was to assess the DNA methylation profile of human spermatozoa during aging. A cohort study was designed to investigate the effects of age and fertility status on sperm DNA methylation.","abstract":"Age-dependent modifications of the germ cells epigenome remain poorly understood. Our objective was to assess the DNA methylation profile of human spermatozoa during aging. A cohort study was designed to investigate the effects of age and fertility status on sperm DNA methylation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-20T15:50:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004169","title":"Chromatin run-on and RNA sequencing of fibrolamellar carcinoma","description":"Fibrolamellar carcinoma (FLC) is a rare, therapeutically intractable liver cancer that disproportionately affects youth. Here we used chromatin run-on sequencing to characterize the enhancer landscape in FLC and RNA sequencing to identify dysregulated genes in FLC.","abstract":"Fibrolamellar carcinoma (FLC) is a rare, therapeutically intractable liver cancer that disproportionately affects youth. Here we used chromatin run-on sequencing to characterize the enhancer landscape in FLC and RNA sequencing to identify dysregulated genes in FLC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-20T20:51:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004170","title":"PIP_A","description":"scRNA-Seq for deceased transplant donor tissues\n\nThe aim of this study is to assess single cell gene expression profiles of immune cells across different human tissues.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"scRNA-Seq for deceased transplant donor tissues\n\nThe aim of this study is to assess single cell gene expression profiles of immune cells across different human tissues.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004171","title":"HCA_WSSS_Adult_Lung_spatial","description":"Human Cell Atlas for lung - Adult spatial work. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). \n\nWSSS Deep Dive for Adult Lung spatial transcriptomics.  This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Human Cell Atlas for lung - Adult spatial work. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). \n\nWSSS Deep Dive for Adult Lung spatial transcriptomics.  This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004172","title":"HCA_Lung_Foetal_WSSS_spatial","description":"Human Cell Atlas for lung - Foetal spatial work. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). \n\nWSSS Deep Dive for Foetal Lung spatial transcriptomics.  This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Human Cell Atlas for lung - Foetal spatial work. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). \n\nWSSS Deep Dive for Foetal Lung spatial transcriptomics.  This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004173","title":"Circulating bacterial DNA as a tool towards non-invasive biomarkers for colorectal cancer and adenoma","description":"The microbiota is closely associated with colorectal neoplasia. This study aims to characterize microbial DNA in plasma samples and identify markers for colorectal neoplasia early detection. We performed whole genome sequencing of cfDNA from 25 colorectal cancer (CRC) patients, 10 colorectal adenoma (CRA) patients and 22 healthy controls (HC). 127 significant bacterial species were identified in the discovery cohort and 28 species were selected by the random forest model, which was tested in the validation cohort and yielded an AUC of 1 for discriminating CRC and CRA from HC. Additionally, bacterial DNA abundance of most marker species in CRA patients were close to levels in CRC or between CRC and HC. In conclusion, we demonstrated alteration of circulating bacterial DNA in colorectal neoplasia patients, suggesting the utility of circulating bacterial biomarkers as a non-invasive tool for colorectal neoplasia screening and early diagnosis.","abstract":"The microbiota is closely associated with colorectal neoplasia. This study aims to characterize microbial DNA in plasma samples and identify markers for colorectal neoplasia early detection. We performed whole genome sequencing of cfDNA from 25 colorectal cancer (CRC) patients, 10 colorectal adenoma (CRA) patients and 22 healthy controls (HC). 127 significant bacterial species were identified in the discovery cohort and 28 species were selected by the random forest model, which was tested in the validation cohort and yielded an AUC of 1 for discriminating CRC and CRA from HC. Additionally, bacterial DNA abundance of most marker species in CRA patients were close to levels in CRC or between CRC and HC. In conclusion, we demonstrated alteration of circulating bacterial DNA in colorectal neoplasia patients, suggesting the utility of circulating bacterial biomarkers as a non-invasive tool for colorectal neoplasia screening and early diagnosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004174","title":"Polyploid hepatocytes are protected from cancer but maintain regenerative capacity in chronic liver disease","description":null,"abstract":"Thirty to ninety percent of hepatocytes contain whole genome duplications, making it imperative to understand the fates and functions of these polyploid cells and how they affect development of liver disease. An important question is how polyploid cells respond to chronic proliferative demands, which are characteristic of liver diseases, but a challenging situation for cells with multiple genomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004175","title":"Whole-exome sequencing of the transposition of the great arteries","description":"Transposition of the great arteries (TGA) is one of the most severe types of congenital heart diseases. Understanding the pathogenesis of TGA is urgently needed for patient management of this severe disease. We sought to systematically examine thegenetic etiology for isolated nonsyndromic TGA using whole-exome sequencing.","abstract":"Transposition of the great arteries (TGA) is one of the most severe types of congenital heart diseases. Understanding the pathogenesis of TGA is urgently needed for patient management of this severe disease. We sought to systematically examine thegenetic etiology for isolated nonsyndromic TGA using whole-exome sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-21T22:56:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004176","title":"Two monogenic disorders masquerading as one: Severe congenital neutropenia with monocytosis and non-syndromic sensorineural hearing loss","description":null,"abstract":"We report a large family with four successive generations, presenting with a complex phenotype of severe congenital neutropenia (SCN), partially penetrant monocytosis, and hearing loss of varying severity. We performed whole exome sequencing to identify the causative variants. \nWe identified and classified a pathogenic GFI1 variant and a likely pathogenic variant in MYO6 which together explain the complex phenotypes seen in this family.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-22T04:40:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004177","title":"The role of the mammalian SWI/SNF chromatin remodeling complex in neuroendocrine prostate cancer","description":"We sought to determine the effects of SMARCA4 and SMARCA2 depletion in prostate cancer cell lines. We performed siRNA-mediated knock-down of SMARCA4 and SMARCA2 in an androgen-sensitive (LNCaP) cell line and in a castration-resistant prostate cancer (CRPC)-adenocarcinoma cell line (22Rv1) and compared global transcriptional alterations using RNA-seq.","abstract":"We sought to determine the effects of SMARCA4 and SMARCA2 depletion in prostate cancer cell lines. We performed siRNA-mediated knock-down of SMARCA4 and SMARCA2 in an androgen-sensitive (LNCaP) cell line and in a castration-resistant prostate cancer (CRPC)-adenocarcinoma cell line (22Rv1) and compared global transcriptional alterations using RNA-seq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-22T08:27:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004178","title":"MSI_Cancer_Models___WGS","description":"The study will use whole genome sequencing to aid in define determinants of WRN dependency in MSI Cancer models.","abstract":"The study will use whole genome sequencing to aid in define determinants of WRN dependency in MSI Cancer models.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-22T14:04:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004179","title":"MSI_Cancer_Models__TGS","description":"The study will use targeted genome sequencing to aid in define determinants of WRN dependency in MSI Cancer models.","abstract":"The study will use targeted genome sequencing to aid in define determinants of WRN dependency in MSI Cancer models.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004180","title":"MSI_Cancer_Models___RNAseq","description":"The study will use RNAseq to aid in define determinants of WRN dependency in MSI Cell lines.","abstract":"The study will use RNAseq to aid in define determinants of WRN dependency in MSI Cell lines.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-22T14:17:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004181","title":"JAK and STAT alterations in CD30 positive LPD","description":null,"abstract":"The group of cutaneous CD30-positive lymphoproliferative disorders (LPD) comprises two different entities, namely lymphomatoid papulosis (LyP) and cutaneous anaplastic large T-cell lymphoma (cALCL). LyP constitutes a benign lymphoproliferation with spontaneously regressing papules, whereas cALCL presents with solitary or multiple skin tumors with a low propensity to disseminate.\nTo elucidate the hitherto largely unknown molecular pathogenesis of these entities, we performed comprehensive next generation sequencing in a well-characterized cohort of 12 patients. Considering the low tumor cell content of LyP, we applied targeted sequencing technologies with a hybrid capture-based DNA library preparation approach and for the identification of fusion transcripts an anchored multiplex PCR enrichment kit.\nAs the major finding, we detected in 50% of LPD genetic events that imply a constitutively activated JAK-STAT pathway in these entities. The identified molecular aberrations comprised either pathogenic STAT mutations or oncogenic fusion transcripts comprising effector domains of JAK. With respect to LyP, we are the first to demonstrate such genetic aberrations in this specific entity, respectively.\nThe detection of these convergent aberrations within the JAK-STAT signaling pathway deciphers common potential driving mechanisms of lymphomagenesis within LPD being shared between LyP and cALCL. Moreover, the presence of these oncogenic alterations paves the way to develop novel personalized treatment strategies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-22T13:45:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004182","title":"Targeted sequencing of breast cancers with germline BRCA1/2 mutations","description":"Breast cancer is the most prevalent cancer in women, where a germline predisposition plays a substantial role. However, the effects of pathogenic germline variants on accompanying breast cancers have not been fully characterized in terms of somatic alterations. We obtained tumor samples from 30 patients with pathogenic germline variants in BRCA2 (n = 25) and BRCA1 (n = 5), as well as an additional 30 patients without pathogenic germline mutations, in which somatic mutations in common breast cancer drivers and CNAs were analyzed using targeted panel sequencing.","abstract":"Breast cancer is the most prevalent cancer in women, where a germline predisposition plays a substantial role. However, the effects of pathogenic germline variants on accompanying breast cancers have not been fully characterized in terms of somatic alterations. We obtained tumor samples from 30 patients with pathogenic germline variants in BRCA2 (n = 25) and BRCA1 (n = 5), as well as an additional 30 patients without pathogenic germline mutations, in which somatic mutations in common breast cancer drivers and CNAs were analyzed using targeted panel sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-22T14:46:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004183","title":"Classifying ultra-high risk multiple myeloma by molecular profiling","description":null,"abstract":"Gene expression profiling of 329 newly diagnosed Multiple Myeloma patients from the NCRI Myeloma XI using SKY92 MMProfiler (SkylineDx, The Netherlands) expression arrays.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004184","title":"HCA_Brain_Disease_ALS_Bayraktar_RNA","description":"Single-nucleus sequencing of ALS and control adult brain samples. In this study, we apply single-nucleus sequencing to ALS and control adult brain samples from multiple cortical brain regions. We aim to understand how, and which, specific cell types, are affected in the known pathophysiological regions in ALS, as well as elucidate commonalities and trends between patients with disparate underlying genetic causes and phenotypic manifestations.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Single-nucleus sequencing of ALS and control adult brain samples. In this study, we apply single-nucleus sequencing to ALS and control adult brain samples from multiple cortical brain regions. We aim to understand how, and which, specific cell types, are affected in the known pathophysiological regions in ALS, as well as elucidate commonalities and trends between patients with disparate underlying genetic causes and phenotypic manifestations.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004185","title":"Pilot_RNA_seq_on_T_cells","description":"Pilot RNA-seq on Tregs and Tcons isolated from whole blood. The cells are in both resting and stimulated conditions. The goal is to produce a reliable RNA-seq dataset to be used in order to explore the gene regulatory landscape of immune cells.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Recently, we identified that immune disease associated variants are enriched in active promoters (marked by H3K4me3 modification) specific to CD4+ regulatory T cells (Tregs).\nThis enrichment suggests that a proportion of associated variants is likely to confer disease risk by modulating gene-expression in this cell type. Here, we aim to further study the effects of disease associated variant - specifically we want to assess if different alleles can lead to imbalanced histone modification levels and altered gene expression. As a pilot, we will perform RNA-seq, ATAC-seq and ChIP-seq for H3K4me3 in Tregs from whole blood of 20 healthy blood donors. All individuals will be also genotyped using a genome-wide array. We will perform assays in stimulated and resting cells.\nBecause this is a large-scale study we want to make sure that our protocols work well on a small subpopulation of cells first. This study will sequence Tregs and Tcons isolated from whole blood obtained commercially for which we performed ATAC library preparation and RNA isolation.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004186","title":"Prostate Cancer mitochondrial DNA heteroplasmies and mitochondrial gene expression","description":null,"abstract":"Altered mitochondrial function in prostate cancer was characterized using paired malignant/non-malignant (benign) tissue samples. Mitochondrial DNA heteroplasmies (mtDNA-NGS) and mitochondria associated gene transcript levels (RNAseq-NGS) were analyzed and correlated to mitochondrial respiration (high-resolution respirometry), to each other and to the tumor stage and grade.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-25T09:24:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004187","title":"Vento_Placental_Cell_Atlas","description":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess human development. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs).","abstract":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess human development. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-27T11:32:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004188","title":"HCA_Brain_Foetal_Bayraktar_Spatial","description":"Spatial analysis HCA Brain Foetal Bayraktar\n\nSpatial analysis of human foetal brain. In this study, we apply NanoString GeoMX Digital Spatial Profiling technology to the human foetal brain in the second trimester. We aim to delineate the gene expression changes associated with the differentiation trajectory from neural stem cells to maturing neurons, as well as examine region-specific differences in cell types and proportions\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Spatial analysis HCA Brain Foetal Bayraktar\n\nSpatial analysis of human foetal brain. In this study, we apply NanoString GeoMX Digital Spatial Profiling technology to the human foetal brain in the second trimester. We aim to delineate the gene expression changes associated with the differentiation trajectory from neural stem cells to maturing neurons, as well as examine region-specific differences in cell types and proportions\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004189","title":"Integrative molecular analysis of pediatric Anaplastic large cell lymphoma reveals subtypes with distinct immune suppression signatures.","description":"Anaplastic large cell lymphoma (ALCL) is a peripheral T-cell lymphoma accounting for 10–15% of all childhood lymphomas. While more than 90% of the ALCL cases contain ALK-rearrangement, these tumors possess significant inter-tumor molecular heterogeneity that contributes to distinct morphologic differences and clinical impact. To gain insight into the molecular heterogeneity within ALK+ ALCL, we performed whole-exome sequencing, RNA-sequencing, and methylome analysis of 42 primary pediatric ALK+ ALCL patients. Our data showed that ALK+ALCLs was subclassified into two subtypes based on ALK gene expression, methylation profiles, and somatic mutation patterns. ALK-low samples had more highly methylated gene regions while enriched with immune infiltration. ALK-high samples were enriched with somatic copy number alteration and high expression of MYC and PD-L1. These data indicate that ALK expression, somatic mutations, and aneuploidy status are negatively associated with immune infiltration, stipulating that ALK expression status might be associated with resistance to immune checkpoint inhibitors.","abstract":"Anaplastic large cell lymphoma (ALCL) is a peripheral T-cell lymphoma accounting for 10–15% of all childhood lymphomas. While more than 90% of the ALCL cases contain ALK-rearrangement, these tumors possess significant inter-tumor molecular heterogeneity that contributes to distinct morphologic differences and clinical impact. To gain insight into the molecular heterogeneity within ALK+ ALCL, we performed whole-exome sequencing, RNA-sequencing, and methylome analysis of 42 primary pediatric ALK+ ALCL patients. Our data showed that ALK+ALCLs was subclassified into two subtypes based on ALK gene expression, methylation profiles, and somatic mutation patterns. ALK-low samples had more highly methylated gene regions while enriched with immune infiltration. ALK-high samples were enriched with somatic copy number alteration and high expression of MYC and PD-L1. These data indicate that ALK expression, somatic mutations, and aneuploidy status are negatively associated with immune infiltration, stipulating that ALK expression status might be associated with resistance to immune checkpoint inhibitors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-27T16:45:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004190","title":"Homologous recombination DNA repair deficiency and activity of PARP inhibition in primary triple negative breast cancer","description":null,"abstract":"To investigate the activity of PARP inhibitors in TNBC, we conducted a translational clinical trial in patients with untreated TNBC with a two week window treatment of the PARP inhibitor rucaparib in 43 patients, the RIO trial . Multiple different approaches identified HR deficiency in the majority of TNBC, 69% with the mutational-signature-based HRDetect assay. Cancers with mutational signatures of HR deficiency had a functional defect in HR.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004191","title":"RNA sequencing of human acute myeloid leukemia after ex vivo treatment with DMSO or indisulam","description":null,"abstract":"Indisulam induces the degradation of the splicing factor RBM39, which may be a therapeutic target in acute myeloid leukemias. To assess indisulam dependent splicing changes in human acute myeloid leukemia, patient cells were isolated and treated ex vivo with DMSO or indisulam. Samples were collected at 0, 6 and 12 hours. RNA isolation was performed using the Direct-zol RNA MiniPrep Plus kit (Zymo Research). An in-column DNase 1 treatment per kit instructions was also performed to eliminate contaminating genomic DNA. RNA was\neluted with nuclease free water and analyzed by an Agilent 2200 TapeStation. Samples with RNA integrity levels greater than 6.5 were used for subsequent analyses. RNA samples for sequencing analysis were submitted to BGI Americas for oligo-dT selection, library preparation, and DNA nanoball synthesis for sequencing on the BGISEQ-500 platform. For detection of splicing events, the SpliceFisher program was utilized.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004192","title":"Transcriptomic response of miRNAs of monocytes to bacterial and viral stimuli assessed by RNA-seq in Africans and Europeans","description":"Leveraging the miRNA transcriptome of 977 samples, the study aims to define the levels of miRNA and isomiR diversity across individuals and populations, explore the genetic sources of miRNA expression variability and miRNA-environment interactions, evaluate the effects of immune challenges upon miRNA and isomiR expression dynamics, and quantify the relative impact of transcription and miRNA-mediated degradation on gene expression variability.","abstract":"Leveraging the miRNA transcriptome of 977 samples, the study aims to define the levels of miRNA and isomiR diversity across individuals and populations, explore the genetic sources of miRNA expression variability and miRNA-environment interactions, evaluate the effects of immune challenges upon miRNA and isomiR expression dynamics, and quantify the relative impact of transcription and miRNA-mediated degradation on gene expression variability.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-29T07:26:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004193","title":"HSC_population_dynamics___KX007_samples","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-29T12:33:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004194","title":"cfRRBS on cfDNA from pediatric cancer","description":"In the clinical management of pediatric solid tumors, histological examination of tumor tissue obtained by a biopsy remains the gold standard to establish a conclusive pathological diagnosis. The DNA methylation pattern of a tumor is known to correlate with the histopathological diagnosis across cancer types and is showing promise in the diagnostic workup of tumor samples. This methylation pattern can be detected in the cell-free DNA. Here, we provide proof-of-concept of histopathologic classification of pediatric tumors using cell-free reduced representation bisulfite sequencing (cf-RRBS) from retrospectively collected plasma and cerebrospinal fluid samples. We determined the correct tumor type in 49 out of 60 (81.6%) samples starting from minute amounts (less than 10 ng) of cell-free DNA. We demonstrate that the majority of misclassifications were associated with sample quality and not with the extent of disease. Our approach has the potential to help tackle some of the remaining diagnostic challenges in pediatric oncology in a cost-effective and minimally invasive manner.","abstract":"In the clinical management of pediatric solid tumors, histological examination of tumor tissue obtained by a biopsy remains the gold standard to establish a conclusive pathological diagnosis. The DNA methylation pattern of a tumor is known to correlate with the histopathological diagnosis across cancer types and is showing promise in the diagnostic workup of tumor samples. This methylation pattern can be detected in the cell-free DNA. Here, we provide proof-of-concept of histopathologic classification of pediatric tumors using cell-free reduced representation bisulfite sequencing (cf-RRBS) from retrospectively collected plasma and cerebrospinal fluid samples. We determined the correct tumor type in 49 out of 60 (81.6%) samples starting from minute amounts (less than 10 ng) of cell-free DNA. We demonstrate that the majority of misclassifications were associated with sample quality and not with the extent of disease. Our approach has the potential to help tackle some of the remaining diagnostic challenges in pediatric oncology in a cost-effective and minimally invasive manner.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-30T07:21:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004195","title":"Sequencing of SWI/SNF complex genes and non-SWI/SNF drivers in lung adenocarcinoma primary tumors and matched normal samples","description":null,"abstract":"The SWI/SNF complex is a multi-protein complex that is known to be involved in various cancers. However, its function and its mechanisms of inactivation in lung adenocarcinoma (LUAD) are largely unknown. Here, we have sequenced the genes of the 20 SWI/SNF subunits that we detected as present in lung based on a previous protein immunoprecipitation assay, as well as 10 non-SWI/SNF LUAD drivers, in 70 LUAD primary tumors and 27 of the matched normal samples (solid adjacent tissue).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004196","title":"pancreatic ductal adenocarcinoma exomes in study: Pro-immunogenic Impact of MEK inhibition combined with an anti-CD40 immunostimulatory antibody","description":"Cancer types with lower mutational load and a non-permissive tumor microenvironment are intrinsically resistant to immune checkpoint blockade. While the combination of cytostatic drugs and immunostimulatory antibodies constitutes an attractive concept for overcoming this refractoriness, suppression of immune cell function by cytostatic drugs may limit therapeutic efficacy. Here we show that targeted inhibition of mitogen-activated protein kinase (MAPK) kinase (MEK) does not impair dendritic cell-mediated T-cell priming and activation. Accordingly, combining MEK inhibitors (MEKi) with agonist antibodies (Abs) targeting the immunostimulatory CD40 receptor resulted in potent synergistic anti-tumor efficacy. Detailed analysis of the mechanism of action of MEKi GDC-0623 by means of flow cytometric analysis of the tumor immune infiltrate and whole tumor transcriptomics showed that, in addition to its cytostatic impact on tumor cells, this drug exerts multiple pro-immunogenic effects, including the suppression of M2-type macrophages, myeloid derived suppressor cells and CD4+ T-regulatory cells. In addition, MEKi was found to induce tumor-cell intrinsic interferon signaling, which contributed to antigen presentation by tumor cells. Finally, the tumoridical impact of MEKi involves the activation of multiple pro-inflammatory pathways involved in immune cell effector function in the tumor microenvironment. Our data therefore indicate that the combination of MEK inhibition with agonist anti-CD40 Ab is a promising therapeutic concept, especially for the treatment of mutant Kras-driven tumors such as pancreatic ductal adenocarcinoma.\nThe pancreatic ductal adenocarcinoma exomes were generated in the context of the Heidelberg Center for Personalized Oncology project HIPO-K28E.","abstract":"Cancer types with lower mutational load and a non-permissive tumor microenvironment are intrinsically resistant to immune checkpoint blockade. While the combination of cytostatic drugs and immunostimulatory antibodies constitutes an attractive concept for overcoming this refractoriness, suppression of immune cell function by cytostatic drugs may limit therapeutic efficacy. Here we show that targeted inhibition of mitogen-activated protein kinase (MAPK) kinase (MEK) does not impair dendritic cell-mediated T-cell priming and activation. Accordingly, combining MEK inhibitors (MEKi) with agonist antibodies (Abs) targeting the immunostimulatory CD40 receptor resulted in potent synergistic anti-tumor efficacy. Detailed analysis of the mechanism of action of MEKi GDC-0623 by means of flow cytometric analysis of the tumor immune infiltrate and whole tumor transcriptomics showed that, in addition to its cytostatic impact on tumor cells, this drug exerts multiple pro-immunogenic effects, including the suppression of M2-type macrophages, myeloid derived suppressor cells and CD4+ T-regulatory cells. In addition, MEKi was found to induce tumor-cell intrinsic interferon signaling, which contributed to antigen presentation by tumor cells. Finally, the tumoridical impact of MEKi involves the activation of multiple pro-inflammatory pathways involved in immune cell effector function in the tumor microenvironment. Our data therefore indicate that the combination of MEK inhibition with agonist anti-CD40 Ab is a promising therapeutic concept, especially for the treatment of mutant Kras-driven tumors such as pancreatic ductal adenocarcinoma.\nThe pancreatic ductal adenocarcinoma exomes were generated in the context of the Heidelberg Center for Personalized Oncology project HIPO-K28E.","study_type":"Other","pubmed_ids":[32358491],"external_links":null,"is_released":true,"released_date":"2020-01-31T12:39:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004197","title":"Immuno-genomic landscape of osteosarcoma","description":"Osteosarcoma is an orphan disease affecting children and young adults that has seen little to no progress in survival outcomes for &gt;30 years. Despite having heavily rearranged genomes, to date, clinical trials with immunotherapy have shown no benefit for patients with osteosarcoma. In this study, we conducted the first multi-platform immune profiling (whole genome, transcriptome, T-cell receptor sequencing, immunohistochemistry and reverse phase protein array) on every available pediatric and adult osteosarcoma patients from our institution (N = 48) with the goal of describing immune features that may contribute to immunotherapy resistance.","abstract":"Osteosarcoma is an orphan disease affecting children and young adults that has seen little to no progress in survival outcomes for &gt;30 years. Despite having heavily rearranged genomes, to date, clinical trials with immunotherapy have shown no benefit for patients with osteosarcoma. In this study, we conducted the first multi-platform immune profiling (whole genome, transcriptome, T-cell receptor sequencing, immunohistochemistry and reverse phase protein array) on every available pediatric and adult osteosarcoma patients from our institution (N = 48) with the goal of describing immune features that may contribute to immunotherapy resistance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-01-31T15:26:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004198","title":"Association of DNA-methylation profiles with immune responses in breast cancer patients","description":null,"abstract":"Immune response to a given antigen, particularly in cancer patients, is complex and is controlled by various genetic and environmental factors. Identifying biomarkers that can predict robust response to immunization is an urgent need in clinical cancer vaccine development. Given the involvement of DNA methylation in the development of lymphocytes, tumorigenicity and tumor progression, we aimed to analyze pre-vaccination DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) from breast cancer subjects vaccinated with a novel peptide-based vaccine referred to as P10s-PADRE. This pilot study was performed to evaluate whether signatures of differentially methylated (DM) loci can be developed as potential predictive biomarkers for prescreening subjects with cancer who will most likely generate an immune response to the vaccine.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004199","title":"Gene expression in brain (Schizophrenia) study","description":"The study included post-mortem brain tissue samples from 68 schizophrenia patients and 44 age and sex matched control subjects. Whole transcriptome poly-A selected paired-end RNA sequencing was performed on tissue from prefrontal cortex and orbitofrontal cortex. RNA expression differences were detected between case and control individuals, focusing both on single genes and pathways.","abstract":"The study included post-mortem brain tissue samples from 68 schizophrenia patients and 44 age and sex matched control subjects. Whole transcriptome poly-A selected paired-end RNA sequencing was performed on tissue from prefrontal cortex and orbitofrontal cortex. RNA expression differences were detected between case and control individuals, focusing both on single genes and pathways.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-03T14:34:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004200","title":"High coverage sequencing of a single sample can account for the problem of intratumor heterogeneity","description":null,"abstract":"Tumor heterogeneity is a consequence of clonal evolution, resulting in a fractal-like architecture with spatially separated main clones, sub-clones and single-cells. Here, we tested the effect of sample size, pooling strategy as well as sequencing depth using next-generation sequencing of ovarian tumor samples. Our results show that sequencing from spatially neighboring regions show similar genetic compositions, with few private mutations. Pooling samples from multiple distinct regions of the primary tumor did not substantially increase the overall number of identified mutations but may increase the robustness of detecting clonal mutations. Hypermutating tumors are a special case, since increasing sample size can easily dilute sub-clonal private mutations below detection thresholds. In view of the limitations of present tools and technologies, single sequencing run per sample combined with high coverage (100-300x) sequencing is affordable and practical, regardless of the number of samples taken from the same patient.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-03T14:47:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004201","title":"StemNet - in vitro differentiation of human hepatocytes","description":"Integrative epigenomic and transcriptomic characterization of hepatocyte-like cells differentiated in vitro from human induced pluripotent stem cells in comparison with primary human hepatocytes. This study comprises single cell RNA-seq, bulk mRNA-seq, ATAC-seq and RRBS.","abstract":"Integrative epigenomic and transcriptomic characterization of hepatocyte-like cells differentiated in vitro from human induced pluripotent stem cells in comparison with primary human hepatocytes. This study comprises single cell RNA-seq, bulk mRNA-seq, ATAC-seq and RRBS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-03T16:08:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004202","title":"Genomic variant analysis of high-risk prostate cancer primary tumour samples","description":"Whole genome sequencing analysis of high risk primary prostate cancer samples was performed with matching germline sequencing data (whole blood). Samples were all fresh frozen section of confirmed tumour specimens.","abstract":"Whole genome sequencing analysis of high risk primary prostate cancer samples was performed with matching germline sequencing data (whole blood). Samples were all fresh frozen section of confirmed tumour specimens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004203","title":"Genetics and transcriptomics of human acute erythroid leukemia","description":null,"abstract":"Acute erythroleukemia (AEL or acute myeloid leukemia [AML]-M6) is a rare but aggressive hematologic malignancy. Previous studies showed that AEL leukemic cells often carry complex karyotypes and mutations in known AML-associated oncogenes. To better define the underlying molecular mechanisms driving the erythroid phenotype, we studied a series of 33 AEL samples representing 3 genetic AEL subgroups including TP53-mutated, epigenetic regulator-mutated (eg, DNMT3A, TET2, or IDH2), and undefined cases with low mutational burden. We established an erythroid vs myeloid transcriptome-based space in which, independently of the molecular subgroup, the majority of the AEL samples exhibited a unique mapping different from both non-M6 AML and myelodysplastic syndrome samples. Notably, &gt;25% of AEL patients, including in the genetically undefined subgroup, showed aberrant expression of key transcriptional regulators, including SKI, ERG, and ETO2. Ectopic expression of these factors in murine erythroid progenitors blocked in vitro erythroid differentiation and led to immortalization associated with decreased chromatin accessibility at GATA1-binding sites and functional interference with GATA1 activity. In vivo models showed development of lethal erythroid, mixed erythroid/myeloid, or other malignancies depending on the cell population in which AEL-associated alterations were expressed. Collectively, our data indicate that AEL is a molecularly heterogeneous disease with an erythroid identity that results in part from the aberrant activity of key erythroid transcription factors in hematopoietic stem or progenitor cells.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-05T10:41:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004204","title":"Whole exome sequencing in familial Multiple Sclerosis","description":"The purpose of the study is to determine whether variants of genes are associated with greater risk of Multiple Sclerosis (MS). We used whole-exome sequencing in 138 individuals from 23 families including at least 2 members with MS. We compare patients with MS, patients with other autoimmune diseases (AID), and unaffected individuals.","abstract":"The purpose of the study is to determine whether variants of genes are associated with greater risk of Multiple Sclerosis (MS). We used whole-exome sequencing in 138 individuals from 23 families including at least 2 members with MS. We compare patients with MS, patients with other autoimmune diseases (AID), and unaffected individuals.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-05T10:51:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004205","title":"Long_read_single_cell_RNaseq_of_human_induced_pluripotent_stem_cells","description":"The human genome is comprised to 50% of transposable elements, however only 1-2% of the transposable elements retained the\nability to change their genomic location. Studying transposable element expression at individual loci in single cells has not been\npossible so far because transposable elements exist in several copies in the genome. Therefore, we are currently working on a\nlong read single cell RNAseq method. We will use human fibroblasts as well as human induced pluripotent stem cells in order to\nunderstand which transposable element loci are expressed during cell dedifferentiation. Sanger will receive DNA/RNA in plate\nformat which will be processed for RNAseq on the pacbio sequencer.\n\nThis study aims to characterise the transcriptionallly active transposable elements in the human genome at single cell and single loci information. For this we have produced single cell long read sequencing data of human fibroblasts as well as induced pluripotent stem cells.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The human genome is comprised to 50% of transposable elements, however only 1-2% of the transposable elements retained the\nability to change their genomic location. Studying transposable element expression at individual loci in single cells has not been\npossible so far because transposable elements exist in several copies in the genome. Therefore, we are currently working on a\nlong read single cell RNAseq method. We will use human fibroblasts as well as human induced pluripotent stem cells in order to\nunderstand which transposable element loci are expressed during cell dedifferentiation. Sanger will receive DNA/RNA in plate\nformat which will be processed for RNAseq on the pacbio sequencer.\n\nThis study aims to characterise the transcriptionallly active transposable elements in the human genome at single cell and single loci information. For this we have produced single cell long read sequencing data of human fibroblasts as well as induced pluripotent stem cells.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004206","title":"Single Cell RNAseq of blood and tumor from renal cancer patients","description":null,"abstract":"Single-cell RNASeq (scRNAseq) showed that IL8 is primarily expressed in circulating and intratumoral myeloid cells and high IL8 expression was associated with the downregulation of the antigen presentation machinery in myeloid cells.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004207","title":"Sex-biased patterns shaped the genetic history of Roma","description":"Whole mtDNA sequences and Y chromosomes from Roma and Non-Roma European samples.","abstract":"Whole mtDNA sequences and Y chromosomes from Roma and Non-Roma European samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-06T15:30:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004208","title":"Pancreatic tropism of metastatic renal cell carcinoma","description":"Renal cell carcinoma (RCC) is characterized by a particularly broad metastatic swath, and enigmatically, when the pancreas is a destination, the disease is associated with improved survival. Intrigued by this observation, we sought to characterize the clinical behavior, therapeutic implications, and underlying biology. While pancreatic metastases (PM) are infrequent, we identified 31 patients across two institutional cohorts and show that improved survival is independent of established prognostic variables, that these tumors are exquisitely sensitive to anti-angiogenic agents and resistant to immune checkpoint inhibitors (ICI), and that they are characterized by a distinctive biology. Primary tumors of patients with PM exhibited frequent PBRM1 mutations, 3p loss, and 5q amplification, along with a lower frequency of aggressive features such as BAP1 mutations and loss of 9p, 14q, and 4q. Gene expression analyses revealed constrained evolution with remarkable uniformity, reduced T-effector gene signatures and increased angiogenesis. Similar findings were observed histopathologically. Thus, RCC metastatic to the pancreas is characterized by indolent biology, heightened angiogenesis, and an uninflamed stroma, likely underlying its good prognosis, sensitivity to anti-angiogenic therapies, and refractoriness to ICI. These data suggest that metastatic organotropism may be an indicator of a particular biology with prognostic and treatment implications for patients.","abstract":"Renal cell carcinoma (RCC) is characterized by a particularly broad metastatic swath, and enigmatically, when the pancreas is a destination, the disease is associated with improved survival. Intrigued by this observation, we sought to characterize the clinical behavior, therapeutic implications, and underlying biology. While pancreatic metastases (PM) are infrequent, we identified 31 patients across two institutional cohorts and show that improved survival is independent of established prognostic variables, that these tumors are exquisitely sensitive to anti-angiogenic agents and resistant to immune checkpoint inhibitors (ICI), and that they are characterized by a distinctive biology. Primary tumors of patients with PM exhibited frequent PBRM1 mutations, 3p loss, and 5q amplification, along with a lower frequency of aggressive features such as BAP1 mutations and loss of 9p, 14q, and 4q. Gene expression analyses revealed constrained evolution with remarkable uniformity, reduced T-effector gene signatures and increased angiogenesis. Similar findings were observed histopathologically. Thus, RCC metastatic to the pancreas is characterized by indolent biology, heightened angiogenesis, and an uninflamed stroma, likely underlying its good prognosis, sensitivity to anti-angiogenic therapies, and refractoriness to ICI. These data suggest that metastatic organotropism may be an indicator of a particular biology with prognostic and treatment implications for patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-06T22:27:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004209","title":"Native American gene flow into Polynesia predating Easter Island settlement","description":"The possibility of voyaging contact between prehistoric Polynesian and Native American populations has long intrigued researchers. Proponents have pointed to the existence of New World crops, such as the sweet potato and bottle gourd, in the Polynesian archaeological record, but nowhere else outside the pre-Columbian Americas while critics have argued that these botanical dispersals need not have been human mediated. The Norwegian explorer Thor Heyerdahl controversially suggested that prehistoric South American populations had an important role in the settlement of east Polynesia and particularly of Easter Island (Rapa Nui). Several limited molecular genetic studies have reached opposing conclusions, and the possibility continues to be as hotly contested today as it was when first suggested. Here we analyse genome-wide variation in individuals from islands across Polynesia for signs of Native American admixture, analysing 807 individuals from 17 island populations and 15 Pacific coast Native American groups. We find conclusive evidence for prehistoric contact of Polynesian individuals with Native American individuals (around AD 1200) contemporaneous with the settlement of remote Oceania. Our analyses suggest strongly that a single contact event occurred in eastern Polynesia, before the settlement of Rapa Nui, between Polynesian individuals and a Native American group most closely related to the indigenous inhabitants of present-day Colombia.","abstract":"The possibility of voyaging contact between prehistoric Polynesian and Native American populations has long intrigued researchers. Proponents have pointed to the existence of New World crops, such as the sweet potato and bottle gourd, in the Polynesian archaeological record, but nowhere else outside the pre-Columbian Americas while critics have argued that these botanical dispersals need not have been human mediated. The Norwegian explorer Thor Heyerdahl controversially suggested that prehistoric South American populations had an important role in the settlement of east Polynesia and particularly of Easter Island (Rapa Nui). Several limited molecular genetic studies have reached opposing conclusions, and the possibility continues to be as hotly contested today as it was when first suggested. Here we analyse genome-wide variation in individuals from islands across Polynesia for signs of Native American admixture, analysing 807 individuals from 17 island populations and 15 Pacific coast Native American groups. We find conclusive evidence for prehistoric contact of Polynesian individuals with Native American individuals (around AD 1200) contemporaneous with the settlement of remote Oceania. Our analyses suggest strongly that a single contact event occurred in eastern Polynesia, before the settlement of Rapa Nui, between Polynesian individuals and a Native American group most closely related to the indigenous inhabitants of present-day Colombia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-07T02:37:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004210","title":"HCA_Female_Reporductive_Adult_WSSS_RNA","description":"Cell atlas of the human placenta\n\nThe Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess human development. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs).\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Cell atlas of the human placenta\n\nThe Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess human development. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs).\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-07T11:02:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004211","title":"Association of DNA-methylation profiles with immune responses in breast cancer patients","description":null,"abstract":"Immune response to a given antigen, particularly in cancer patients, is complex and is controlled by various genetic and environmental factors. Identifying biomarkers that can predict robust response to immunization is an urgent need in clinical cancer vaccine development. Given the involvement of DNA methylation in the development of lymphocytes, tumorigenicity and tumor progression, we aimed to analyze pre-vaccination DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) from breast cancer subjects vaccinated with a novel peptide-based vaccine referred to as P10s-PADRE.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-07T14:56:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004212","title":"The application of RNA sequencing for the diagnosis and genomic classification of pediatric acute lymphoblastic leukemia","description":"Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy, and\nimplementation of risk-adapted therapy has been instrumental in the dramatic improvements in\nclinical outcomes. A key to risk-adapted therapies includes the identification of genomic features of\nindividual tumors, including chromosome number (for hyper- and hypodiploidy) and gene fusions,\nnotably ETV6-RUNX1, TCF3-PBX1 and BCR-ABL1 in B-cell ALL (B-ALL). RNA-sequencing\n(RNA-seq) of large ALL cohorts has expanded the number of recurrent gene fusions recognized as\ndrivers in ALL, and identification of these new entities will contribute to refining ALL risk\nstratification. We used RNA-seq on 126 ALL patients from our clinical service to test the utility of\nincluding RNA-seq in standard of care diagnostic pipelines to detect gene rearrangements and\nIKZF1 deletions. RNA-seq identified 86% of rearrangements detected by standard of care\ndiagnostics. KMT2A-rearrangements (MLL), whilst usually identified, were the most commonly\nmissed by RNA-seq as a result of low expression. RNA-seq identified rearrangements that were not\ndetected by standard of care testing in nine patients. These were found in patients who were not\nclassifiable using standard molecular assessment. We developed an approach to detect the\ncommonest IKZF1 deletion from RNA-seq data and validated this using a RQ-PCR assay. We\napplied an expression classifier to identify Ph-like B-ALL patients. T-ALL proved a rich source of\nnovel gene fusions which have clinical implications or provide insights into disease biology. Our\nexperience shows that RNA-seq can be implemented within an individual clinical service to\nenhance the current molecular diagnostic risk classification of ALL.","abstract":"Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy, and\nimplementation of risk-adapted therapy has been instrumental in the dramatic improvements in\nclinical outcomes. A key to risk-adapted therapies includes the identification of genomic features of\nindividual tumors, including chromosome number (for hyper- and hypodiploidy) and gene fusions,\nnotably ETV6-RUNX1, TCF3-PBX1 and BCR-ABL1 in B-cell ALL (B-ALL). RNA-sequencing\n(RNA-seq) of large ALL cohorts has expanded the number of recurrent gene fusions recognized as\ndrivers in ALL, and identification of these new entities will contribute to refining ALL risk\nstratification. We used RNA-seq on 126 ALL patients from our clinical service to test the utility of\nincluding RNA-seq in standard of care diagnostic pipelines to detect gene rearrangements and\nIKZF1 deletions. RNA-seq identified 86% of rearrangements detected by standard of care\ndiagnostics. KMT2A-rearrangements (MLL), whilst usually identified, were the most commonly\nmissed by RNA-seq as a result of low expression. RNA-seq identified rearrangements that were not\ndetected by standard of care testing in nine patients. These were found in patients who were not\nclassifiable using standard molecular assessment. We developed an approach to detect the\ncommonest IKZF1 deletion from RNA-seq data and validated this using a RQ-PCR assay. We\napplied an expression classifier to identify Ph-like B-ALL patients. T-ALL proved a rich source of\nnovel gene fusions which have clinical implications or provide insights into disease biology. Our\nexperience shows that RNA-seq can be implemented within an individual clinical service to\nenhance the current molecular diagnostic risk classification of ALL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-09T09:28:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004213","title":"Real-time response profiling through serial plasma analyses during FOLFOX treatment in patients with colorectal cancer","description":"Response evaluation of cancer therapeutics relies on the assessment of the change in tumor burden, which is performed in accordance with defined criteria every 8-12 weeks. However, predictive factors for response are not available for the majority of patients with advanced stage colorectal cancer. Here we show that measurement of circulating tumor DNA (ctDNA) levels during one of the most commonly administered drug regimens, i.e. FOLFOX, allows an early, real-time assessment of treatment response. During the 48-hour FOLFOX application, we serially assessed plasma DNA and observed that ctDNA levels initially decreased during the first 23 hours. In patients with stable disease or partial response, ctDNA levels remained low, whereas in patients with progressive disease, ctDNA levels increased at the end of the treatment cycle predicting clinical and radiologic response correctly. Hence, ctDNA monitoring during treatment may contribute to an early outcome prediction with significant implications for the management of patients.","abstract":"Response evaluation of cancer therapeutics relies on the assessment of the change in tumor burden, which is performed in accordance with defined criteria every 8-12 weeks. However, predictive factors for response are not available for the majority of patients with advanced stage colorectal cancer. Here we show that measurement of circulating tumor DNA (ctDNA) levels during one of the most commonly administered drug regimens, i.e. FOLFOX, allows an early, real-time assessment of treatment response. During the 48-hour FOLFOX application, we serially assessed plasma DNA and observed that ctDNA levels initially decreased during the first 23 hours. In patients with stable disease or partial response, ctDNA levels remained low, whereas in patients with progressive disease, ctDNA levels increased at the end of the treatment cycle predicting clinical and radiologic response correctly. Hence, ctDNA monitoring during treatment may contribute to an early outcome prediction with significant implications for the management of patients.","study_type":"Other","pubmed_ids":[33299124],"external_links":null,"is_released":true,"released_date":"2020-02-10T10:08:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004214","title":"Analysis of exonic somatic variants in light-chain amyloidosis (ALA) and ALA concomitant with multiple myeloma","description":"We aim to provide the very first insight into ALA+MM molecular profiles and compare the results with ALA and with MM. Our detailed study of ALA and ALA+MM represents an important step towards improved understanding of their genetic and transcriptomic background, which is a prerequisite for development of optimal treatment strategies in the future.","abstract":"We aim to provide the very first insight into ALA+MM molecular profiles and compare the results with ALA and with MM. Our detailed study of ALA and ALA+MM represents an important step towards improved understanding of their genetic and transcriptomic background, which is a prerequisite for development of optimal treatment strategies in the future.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-10T11:43:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004215","title":"Genomic landscapes of endometrioid and mucinous ovarian cancers","description":"Endometrioid and mucinous ovarian cancers represent nearly a quarter of ovarian cancers and their molecular characteristics and pathologic origins are poorly understood.  To uncover the genomic alterations of these ovarian cancer subtypes and evaluate links to morphologically similar tumors from other sites, we performed sequence, copy number, mutation signature and rearrangement analyses using whole exome or whole genome sequencing from tumors samples of 117 patients.  These included patients with ovarian endometrioid (36), ovarian mucinous (36), uterine endometrial (15), and gastrointestinal mucinous cancers (30).  In addition to identifying genes previously known to be involved in these tumors, we identified novel alterations in RAD51C, NOTCH4, SMARCA4, SMARCA1 and JAK1 in ovarian endometrioid, ESR1 in uterine endometrioid, and SMARCA4 in ovarian mucinous cancers.  Whole genome sequencing revealed novel rearrangements involving PTEN, NF1, and NF2 in ovarian endometrioid tumors, and NF1 and MED1 in ovarian mucinous cancers.  Integrating sequence, copy number, rearrangement, and methylation changes identified specific genes that were differentially altered in ovarian and GI mucinous cancers, suggesting that these tumors have different cell types of origin.  Similarly, methylation analyses of ovarian and GI mucinous tumors and their adjacent normal tissues indicated that these tumors were epigenetically distinct.  In contrast, the number of alterations and affected genes in ovarian and uterine endometrioid cancers were not distinguishable, suggesting that these tumors may have a similar tissue of origin.  These analyses provide insights into the genomic landscapes and origins of mucinous and endometrioid ovarian carcinomas, providing new avenues for early clinical intervention and management of patients with these cancers.","abstract":"Endometrioid and mucinous ovarian cancers represent nearly a quarter of ovarian cancers and their molecular characteristics and pathologic origins are poorly understood.  To uncover the genomic alterations of these ovarian cancer subtypes and evaluate links to morphologically similar tumors from other sites, we performed sequence, copy number, mutation signature and rearrangement analyses using whole exome or whole genome sequencing from tumors samples of 117 patients.  These included patients with ovarian endometrioid (36), ovarian mucinous (36), uterine endometrial (15), and gastrointestinal mucinous cancers (30).  In addition to identifying genes previously known to be involved in these tumors, we identified novel alterations in RAD51C, NOTCH4, SMARCA4, SMARCA1 and JAK1 in ovarian endometrioid, ESR1 in uterine endometrioid, and SMARCA4 in ovarian mucinous cancers.  Whole genome sequencing revealed novel rearrangements involving PTEN, NF1, and NF2 in ovarian endometrioid tumors, and NF1 and MED1 in ovarian mucinous cancers.  Integrating sequence, copy number, rearrangement, and methylation changes identified specific genes that were differentially altered in ovarian and GI mucinous cancers, suggesting that these tumors have different cell types of origin.  Similarly, methylation analyses of ovarian and GI mucinous tumors and their adjacent normal tissues indicated that these tumors were epigenetically distinct.  In contrast, the number of alterations and affected genes in ovarian and uterine endometrioid cancers were not distinguishable, suggesting that these tumors may have a similar tissue of origin.  These analyses provide insights into the genomic landscapes and origins of mucinous and endometrioid ovarian carcinomas, providing new avenues for early clinical intervention and management of patients with these cancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004216","title":"Novel manifestations of immune dysregulation and granule defects in gray platelet syndrome","description":"Gray Platelet Syndrome (GPS) is a rare recessive bleeding disorder resulting from biallelic variants in NBEAL2. As part of a comprehensive evaluation of the phenotype and genotype in 47 patients with GPS, four different blood cell-types (platelets, neutrophils, monocytes, and CD4-lymphocytes) were evaluated using bulk RNA-seq in five patients and five controls. These data are deposited in this archive in FASTQ format.","abstract":"Gray Platelet Syndrome (GPS) is a rare recessive bleeding disorder resulting from biallelic variants in NBEAL2. As part of a comprehensive evaluation of the phenotype and genotype in 47 patients with GPS, four different blood cell-types (platelets, neutrophils, monocytes, and CD4-lymphocytes) were evaluated using bulk RNA-seq in five patients and five controls. These data are deposited in this archive in FASTQ format.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-10T16:39:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004217","title":"Whole exome sequencing from early stage non-small cell lung cancer patients at MDACC.","description":null,"abstract":"To identify genomic drivers present in early-stage non-small cell lung cancer; To determine the overall tumor mutational burden in early-stage non-small cell lung cancer.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004218","title":"HDAC3 mediates the inflammatory response and LPS tolerance in human monocytes and macrophages","description":null,"abstract":"Identifying the effect of HDAC3i (ITF3100) on M1 macrophages that have undergone 0 (N), 1 (NT), or 2 (T) LPS treatments. Processed data can be found in ArrayExpress at E-MTAB-8784.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-12T07:19:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004219","title":"Stabilising selection causes grossly altered but stable karyotypes in metastatic colorectal cancer","description":null,"abstract":"In colorectal cancer (CRC), aneuploidy is found in virtually all tumours, including precursor adenomas. However, the temporal evolutionary dynamics that select for aneuploidy remain broadly uncharacterised. Using these samples we perform genomic analysis of 755 samples from a total of 167 patients with colorectal-derived neoplastic lesions that cross-sectionally represent the distinct stages of tumour evolution, and longitudinally track individual tumours through metastasis and treatment.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-01-19T11:01:29.04679+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004220","title":"KDM4A regulates the maternal-to-zygotic transition by protecting broad H3K4me3 domains from H3K9me3 invasion in oocytes","description":null,"abstract":"The importance of germline-inherited posttranslational histone modification in priming early mammalian development is just emerging1-4. Histone H3 lysine 9 (H3K9) trimethylation is associated with heterochromatin and gene repression during cell-fate change5, while histone H3 lysine 4 (H3K4) trimethylation marks active gene promoters6. Mature oocytes are transcriptionally quiescent and possess remarkably broad domains of H3K4me3 (bdH3K4me3)1, 2. It remains unknown, which factors contribute to the maintenance of the bdH3K4me3 landscape. Lysine-specific demethylase 4A (KDM4A) demethylates H3K9me3 at promoters marked by H3K4me3 in actively transcribing somatic cells7. Here, we report that KDM4A-mediated H3K9me3 demethylation at bdH3K4me3 in oocytes is crucial for normal preimplantation development and zygotic genome activation (ZGA) after fertilization. Loss of KDM4A in oocytes causes extensive and aberrant H3K9me3 spreading at bdH3K4me3, resulting in insufficient transcriptional activation ZGA genes, endogenous retroviral elements and long terminal repeat -initiated chimeric transcripts in 2-cell embryos. The catalytic activity of KDM4A is essential for normal epigenetic reprogramming and preimplantation development. Hence, KDM4A plays a crucial role in preserving maternal epigenome integrity required for proper ZGA and transfer of developmental control to the embryo.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-12T13:44:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004221","title":"Whole-genome DNA methylation profiling of CD14+ monocytes reveals disease status and activity differences in Crohn’s disease patients","description":"Identifying differences in CD14+ monocyte methylation between CD and non-CD patients, as well as between CD-active and CD-remissive patients.","abstract":"Identifying differences in CD14+ monocyte methylation between CD and non-CD patients, as well as between CD-active and CD-remissive patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-12T13:46:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004222","title":"Whole exome sequencing of human T-cell acute lymphoblastic leukemia samples with an oncogenic NOTCH1 mutant","description":null,"abstract":"Genomic DNA was extracted from 4 independent human T-cell acute lymphoblastic leukemia samples arising in immunodeficient mice after transplantation of 3 donors-pooled hematopietic stem cell progenitors transduced with an oncogenic NOTCH1 mutant.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004223","title":"Whole Exome Sequencing of blood samples of a cutaneous T-cell lymphoma patient","description":null,"abstract":"Genomic DNA was extracted from 4 cell subtypes isolated from the blood of a cutaneous T-cell lymphoma patient: normal granulocytes (AD6133), leukemic CD4+ blasts (AD6134), and 2 phenotypically different populations of CD4+ T lymphocytes (AD6135 and AD6136).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004224","title":"CYPTAM - PacBio SMRT sequencing","description":null,"abstract":"Pharmacogenomics is a key component of precision medicine. It promises to prevent adverse drug reactions and reduce ineffective treatment by individualizing the choice of drug and dose based on an individual’s genetic profile. The majority of commonly prescribed drugs are metabolized by a small set of Cytochrome P450 (CYP) enzymes. Currently, a subset of genetic biomarkers are used to categorize patients into predefined *-alleles to predict CYP450 enzyme activity. Yet, this approach cannot describe all genetic variability in drug response, with a large degree of unpredictability remaining. We have combined long-read PacBio sequencing with a neural network to improve phenotype prediction in pharmacogenetics. \nFor 566 breastcancer patients who have used the CYp2D6 substrate tamoxifen as adjuvant therapy, we have sequenced the full CYP2D6 locus using PacBio SMRT sequencing. CYP2D6 enzyme activity can be inferred from the tamoxifen metabolism by using the ratio between the metabolites endoxifen and desmethyltamoxifen (Metabolic ratio (MR)). This MR was used as a proxy for observed CYP2D6 enzyme activity and is regarded as the true phenotype. The PacBio sequencing + neural network approach explained 79% of the interindividual variability in CYP2D6 activity compared to 55% with the conventional approach.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-12T15:58:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004225","title":"Whole exome sequencing of xenografts preleukemic T cell populations expressing oncogenic NOTCH1 mutant","description":null,"abstract":"Whole exome sequencing was performed on CD34+ human hematopoietic stem cell progenitors from a single donor (AD6152), and the following independent xenografts arising in the bone marrow of transplanted immunodeficient mice: 4 independent human pre-leukemic DP T cell populations expressing an oncogenic NOTCH1 mutant (AD6154, AD6156, AD6158, and AD6160), and the corresponding B lymphocyte samples isolated from the same recipients (AD6153, AD6155, AD6157, and AD6159).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004226","title":"Normothermic machine perfusion of Human Kidneys prior to transplantation","description":null,"abstract":"RNASeq was performed on kidneys prior to transplantation which had undergone 1 hr of Normothermic machine perfusion. We then used this data to identify gene signatures that correlate with length of delayed graft function.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004227","title":"Genomic and transcriptomic analysis of thymic epithelial tumors","description":"Thymic epithelial tumors (TETs), comprising various histologic types of thymomas and thymic carcinomas, originate from thymic epithelial cells. Each histologic type is typically associated with a distinct immune cell composition and clinical manifestation. A better understanding of the cellular origins and molecular pathways underlying this heterogeneity is needed to improve patient stratification and treatment. Here, we conducted an integrated genomic and transcriptomic analysis of 124 thymomas and 13 thymic carcinomas, including 20 newly sequenced cases combined with 117 cases from publicly available datasets. This approach stratified TETs into three subgroups with different possible origins: GTF2I-mutant (GTF2I-type) thymomas, copy number-altered (CN-type) thymomas, and thymic carcinomas.","abstract":"Thymic epithelial tumors (TETs) are rare neoplasms with a low somatic mutation rate and a lack of effective systemic treatment. Despite a few previous efforts, no remarkable driver mutations have been identified from ~50% of thymomas, especially in more aggressive histological types. Throughout integrative analyses of the exome, whole-genome, and transcriptome sequencing, here we show distinct tumorigenic processes in thymic epithelial cells.","study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-06T12:53:20.61527+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004228","title":"Heterogeneous Genomic Evolution and Immune Microenvironments in Metastatic Lung Cancer","description":"The mechanism underlying the occurrence of lung cancer metastasis to different tissues/organs remains elusive. We investigated the genomic evolution and immune microenvironments of paired primary-metastatic tumors by employing multi-region whole-exome sequencing in 179 samples of 106 tumors from 51 lung cancer patients and subsequent immunohistochemistry assays in 70 of them. Our data revealed differences in genomic landscapes, molecular determinants, evolutionary dynamics, and lymphocyte infiltration among different metastatic sites. We demonstrated commonly late arising of metastatic seeding of lung cancer with quantitative evidence. Most distant metastases originated from independent origins of earlier lymph node spreads. Immune-heterogeneity and -homogeneity were primarily driven by arm-level and focal copy number events in primary tumors, respectively. These findings implied the combinatorial role of multiple factors in shaping patterns of dissemination and advanced the clinical evaluation and intervention of lung cancer metastasis.","abstract":"The mechanism underlying the occurrence of lung cancer metastasis to different tissues/organs remains elusive. We investigated the genomic evolution and immune microenvironments of paired primary-metastatic tumors by employing multi-region whole-exome sequencing in 179 samples of 106 tumors from 51 lung cancer patients and subsequent immunohistochemistry assays in 70 of them. Our data revealed differences in genomic landscapes, molecular determinants, evolutionary dynamics, and lymphocyte infiltration among different metastatic sites. We demonstrated commonly late arising of metastatic seeding of lung cancer with quantitative evidence. Most distant metastases originated from independent origins of earlier lymph node spreads. Immune-heterogeneity and -homogeneity were primarily driven by arm-level and focal copy number events in primary tumors, respectively. These findings implied the combinatorial role of multiple factors in shaping patterns of dissemination and advanced the clinical evaluation and intervention of lung cancer metastasis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-14T16:25:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004229","title":"NanoSring of PBMC from bladder cancer and RCC patients","description":"PBMCs from patients were isolated using 50 mL Leucosep™ tubes (Greiner Bio-One International, Germany) and Ficoll-Paque™ PLUS (GE Healthcare, Sweden). Whole blood drawn into sodium heparin blood collection tubes were diluted 3x with phosphate-buffered saline (PBS) without calcium or magnesium (Lonza, Walkersville, MD). Diluted cell suspensions were carefully layered on Leucosep tubes and centrifuged for 15 minutes at 800 x g at room temperature (RT). Interphase containing PBMCs were harvested and washed with PBS and subsequently centrifuged for 10 minutes at 250 x g at RT before further processing.","abstract":"PBMCs from patients were isolated using 50 mL Leucosep™ tubes (Greiner Bio-One International, Germany) and Ficoll-Paque™ PLUS (GE Healthcare, Sweden). Whole blood drawn into sodium heparin blood collection tubes were diluted 3x with phosphate-buffered saline (PBS) without calcium or magnesium (Lonza, Walkersville, MD). Diluted cell suspensions were carefully layered on Leucosep tubes and centrifuged for 15 minutes at 800 x g at room temperature (RT). Interphase containing PBMCs were harvested and washed with PBS and subsequently centrifuged for 10 minutes at 250 x g at RT before further processing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-14T19:59:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004230","title":"Single Cell RNAseq of blood and tumor from renal cancer patients","description":"Single-cell RNASeq (scRNAseq) showed that IL8 is primarily expressed in circulating and intratumoral myeloid cells and high IL8 expression was associated with the downregulation of the antigen presentation machinery in myeloid cells.","abstract":"Single-cell RNASeq (scRNAseq) showed that IL8 is primarily expressed in circulating and intratumoral myeloid cells and high IL8 expression was associated with the downregulation of the antigen presentation machinery in myeloid cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-14T21:35:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004231","title":"Whole exome sequencing of chemotherapy-resistant muscle-invasive urothelial bladder cancer","description":null,"abstract":"All exome sequencing data were acquired from single patients (BC159T) at a different time (BC159-T#1, BC159-T#2, and BC159-T#3). The first transurethral resection of bladder tumor (TUR-BT) (BC159-T#1) was diagnosed with non-MIUBC (muscle-invasive urothelial bladder cancer). Despite of intravesical bacillus Calmette-Guerin (BCG), the patient progressed into MIUBC at the second TUR-BT (BC159-T#2). After undergoing multiple neoadjuvant chemotherapy regimens (gemcitabine/paclitaxel and sequential paclitaxel), the patient developed local recurrence and multiple lung metastases and removed following palliative partial cystectomy (BC159-T#3).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-16T06:05:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004232","title":"Whole transcriptome sequencing of chemotherapy-resistant muscle-invasive urothelial bladder cancer","description":"All mRNA sequencing data were acquired from single patients (BC159T) at a different time (BC159-T#1, BC159-T#2, and BC159-T#3). The first transurethral resection of bladder tumor (TUR-BT) (BC159-T#1) was diagnosed with non-MIUBC (muscle-invasive urothelial bladder cancer). Despite of intravesical bacillus Calmette-Guerin (BCG), the patient progressed into MIUBC at the second TUR-BT (BC159-T#2). After undergoing multiple neoadjuvant chemotherapy regimens (gemcitabine/paclitaxel and sequential paclitaxel), the patient developed local recurrence and multiple lung metastases and removed following palliative partial cystectomy (BC159-T#3).","abstract":"All mRNA sequencing data were acquired from single patients (BC159T) at a different time (BC159-T#1, BC159-T#2, and BC159-T#3). The first transurethral resection of bladder tumor (TUR-BT) (BC159-T#1) was diagnosed with non-MIUBC (muscle-invasive urothelial bladder cancer). Despite of intravesical bacillus Calmette-Guerin (BCG), the patient progressed into MIUBC at the second TUR-BT (BC159-T#2). After undergoing multiple neoadjuvant chemotherapy regimens (gemcitabine/paclitaxel and sequential paclitaxel), the patient developed local recurrence and multiple lung metastases and removed following palliative partial cystectomy (BC159-T#3).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-16T06:05:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004233","title":"Single-cell RNA sequencing of chemotherapy-resistant muscle-invasive urothelial bladder cancer","description":"All single-cell mRNA sequencing data were acquired from a single patient (BC159-T#3) and patient-derived xenografts (BC159-T#3-PDX-vehicle and BC159-T#3-PDX-tipifarnib).","abstract":"All single-cell mRNA sequencing data were acquired from a single patient (BC159-T#3) and patient-derived xenografts (BC159-T#3-PDX-vehicle and BC159-T#3-PDX-tipifarnib).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-16T06:05:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004234","title":"Targetted resequencing candidate genes Keratoconus","description":null,"abstract":"The involvement of genetic factors in the pathogenesis of Keratoconus (KC) has long been recognized but the identification of pathogenic variants has been challenging. In this study, we selected 34 candidate genes for KC based on previous Whole Exome Sequencing (WES) and the literature, and resequenced them in 745 KC patients and 810 ethnically matched controls.  Data analysis was performed using the single variant association test as well as gene-based mutation burden and variance components tests. \nIn our study, we detected enrichment of genetic variation across multiple gene-based tests for the genes COL2A1, COL5A1, TNXB, ZEB1 and ZNF469. The top hit in the Fisher’s exact test was obtained for a common variant in the COL12A1 gene. Interestingly, COL5A1, TNXB, ZNF469 and COL12A1 are all known Ehlers-Danlos Syndrome (EDS) genes. Though the co-occurrence of KC and EDS has been reported previously, this study is the first to demonstrate a consistent role of genetic variants in EDS genes in the etiology of KC. In conclusion, our data show a shared genetic etiology between KC and EDS, and clearly confirm the currently disputed role of ZNF469 in disease susceptibility for KC. Besides the role for EDS genes, we also confirm the previously reported involvement of genetic variation in ZEB1 in KC.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004235","title":"Exome sequencing of familial high-grade serous ovarian carcinoma reveals heterogeneity for rare candidate susceptibility genes","description":"High-grade serous ovarian carcinoma (HGSOC) has a significant hereditary component, approximately half of which cannot be explained by known genes. To discover genes, we analyse germline exome sequencing data from 516 BRCA1/2-negative women with HGSOC, focusing on genes enriched with rare, protein-coding loss-of-function (LoF) variants. Overall, there is a significant enrichment of rare protein-coding LoF variants in the cases (p &lt; 0.0001, chi-squared test). Only thirty-four (6.6%) have a pathogenic variant in a known or proposed predisposition gene. Few genes have LoF mutations in more than four individuals and the majority are detected in one individual only. Forty-three highly-ranked genes are identified with three or more LoF variants that are enriched by three-fold or more compared to GnomAD. These genes represent diverse functional pathways with relatively few involved in DNA repair, suggesting that much of the remaining heritability is explained by previously under-explored genes and pathways.","abstract":"High-grade serous ovarian carcinoma (HGSOC) has a significant hereditary component, approximately half of which cannot be explained by known genes. To discover genes, we analyse germline exome sequencing data from 516 BRCA1/2-negative women with HGSOC, focusing on genes enriched with rare, protein-coding loss-of-function (LoF) variants. Overall, there is a significant enrichment of rare protein-coding LoF variants in the cases (p &lt; 0.0001, chi-squared test). Only thirty-four (6.6%) have a pathogenic variant in a known or proposed predisposition gene. Few genes have LoF mutations in more than four individuals and the majority are detected in one individual only. Forty-three highly-ranked genes are identified with three or more LoF variants that are enriched by three-fold or more compared to GnomAD. These genes represent diverse functional pathways with relatively few involved in DNA repair, suggesting that much of the remaining heritability is explained by previously under-explored genes and pathways.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-18T09:30:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004236","title":"iNeuron_ATACseq","description":"Characterisation of a timecourse of differentiation of induced cortical excitatory neurons generated by overexpression of the Ngn2 transcription factor transgenically in BOB iPSCs. The aim is to understand the differentiation trajectory undergone in this process, and characterise the accessible chromatin in these cells for further disease modelling.  \n\nThis data has been described in the following article [doi or ref] and its further analysis can be freely submitted for publication. For information on the proper use of data shared by the Wellcome Trust Sanger Institute please see  http://www.sanger.ac.uk/datasharing/","abstract":"Characterisation of a timecourse of differentiation of induced cortical excitatory neurons generated by overexpression of the Ngn2 transcription factor transgenically in BOB iPSCs. The aim is to understand the differentiation trajectory undergone in this process, and characterise the accessible chromatin in these cells for further disease modelling.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004237","title":"The_Little_Princess_Knowledge_Bank_","description":"We propose to build a genetic knowledge bank of Wilms tumour that integrates clinical outcome\ndata with a genetic, epigenetic, and transcriptomic survey of 1,000 Wilms tumours.","abstract":"The purpose of the knowledge bank is to serve as a community resource and to address the following specific\nquestions about Wilms tumour:\n(1) Do genetic, epigenetic, or transcriptional features predict outcome and thus lend themselves to\ntreatment stratification?\n(2) What are the genetic drivers of Wilms tumour, considering the entire histological spectrum of\nWilms tumour including the most common subtypes classified as intermediate risk?","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-18T14:41:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004238","title":"iNeuron_RNAseq","description":"Characterisation of a timecourse of differentiation of induced cortical excitatory neurons generated by overexpression of the Ngn2 transcription factor transgenically in BOB iPSCs. The aim is to understand the differentiation trajectory undergone in this process, and characterise the transcriptome in these cells for further disease modelling.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Characterisation of a timecourse of differentiation of induced cortical excitatory neurons generated by overexpression of the Ngn2 transcription factor transgenically in BOB iPSCs. The aim is to understand the differentiation trajectory undergone in this process, and characterise the transcriptome in these cells for further disease modelling.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-18T15:53:18+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004239","title":": Centromeric cohesion failure invokes a conserved choreography of chromosomal mis-segregations in pancreatic neuroendocrine tumours","description":null,"abstract":"Pancreatic neuroendocrine tumours (PANETs) are rare, slow growing cancers that often present with local and distant metastasis upon detection. PANETS contain distinct karyotypes, epigenetic dysregulation, and recurrent mutations in MEN1, ATRX and DAXX (MAD+); however, the molecular basis of disease progression remains uncharacterized. We evaluated associations between aneuploidy and the MAD+ mutational state of 532 PANETs. Using this data, we propose an evolutionary model for a subset of aggressive PANETs that is initiated by mutation of MEN1, ATRX and DAXX, resulting in defects in centromere cohesion from ectopic CENP-A deposition that leads to selective loss of chromosomes and the LOH phenotype seen in late-stage metastatic PANETs.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-18T20:01:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004240","title":"Comprehensive analysis of genomes and transcriptomes reveals the potential mechanism and targets of low-grade myofibroblastic sarcoma","description":"Low-grade myofibroblastic sarcoma (LGMS) is a rare type of tumor, whose molecular mechanism has not been fully elucidated. In a progressive LGMS case, we found that apatinib significantly improved the patient’ss' quality of life and survival. MethodsWe extracted tumor tissue and matched adjacent normal tissues from an LGMS patients, which were subjectedwholesubjected to whole- exomen sequencing (WES) and RNA-sequence sequencing (RNA-seq). Annotating The genes were annotated for genomic and transcript mutations, displaying genes for transcriptional disorders mediated by genomic variation. Genomic alterations in cancer, including single-nucleotide variations (SNVs), copy number variations (CNVs) and differentially expressed genes (DEGs) were represented in Circos plots. Subsequently, functional enrichment analysis was applied to explore the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in LGMS, which affecting were affected by the DEGs.ResultsIn whole exon sequencingWES showed that, 256 genes may be related to SNVs,; at the same timesimultaneously, 269 genes may be related to CNVs. In addition, we identified 252 DEGs byin RNA-seq totally. The bBiological Pprocesses including involved “the regulation of extracellular structure organization” and “humoral immune response mediated by circulating immunoglobulin” weare enriched in the LGMS samples. KEGG pathwaypathways, including the phosphatidylinositol 3-kinase (PI3K) signaling pathway, the Neuroactiveneuroactive ligand-receptor interaction-signaling pathway, and the cAMP signaling pathway, were enriched in the LGMS samples. Finally, we exploreexplored the potential mechanism of apatinib into LGMS duringin the patient's treatment process.Conclusions We found that apatinib may inhibiteinhibit tumor growth and down regulatedownregulate the PI3K signaling pathway, which indicated that apatinib may be a novalnovel and potential drug for LGMS treatments.","abstract":"Low-grade myofibroblastic sarcoma (LGMS) is a rare type of tumor, whose molecular mechanism has not been fully elucidated. In a progressive LGMS case, we found that apatinib significantly improved the patient’ss' quality of life and survival. MethodsWe extracted tumor tissue and matched adjacent normal tissues from an LGMS patients, which were subjectedwholesubjected to whole- exomen sequencing (WES) and RNA-sequence sequencing (RNA-seq). Annotating The genes were annotated for genomic and transcript mutations, displaying genes for transcriptional disorders mediated by genomic variation. Genomic alterations in cancer, including single-nucleotide variations (SNVs), copy number variations (CNVs) and differentially expressed genes (DEGs) were represented in Circos plots. Subsequently, functional enrichment analysis was applied to explore the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in LGMS, which affecting were affected by the DEGs.ResultsIn whole exon sequencingWES showed that, 256 genes may be related to SNVs,; at the same timesimultaneously, 269 genes may be related to CNVs. In addition, we identified 252 DEGs byin RNA-seq totally. The bBiological Pprocesses including involved “the regulation of extracellular structure organization” and “humoral immune response mediated by circulating immunoglobulin” weare enriched in the LGMS samples. KEGG pathwaypathways, including the phosphatidylinositol 3-kinase (PI3K) signaling pathway, the Neuroactiveneuroactive ligand-receptor interaction-signaling pathway, and the cAMP signaling pathway, were enriched in the LGMS samples. Finally, we exploreexplored the potential mechanism of apatinib into LGMS duringin the patient's treatment process.Conclusions We found that apatinib may inhibiteinhibit tumor growth and down regulatedownregulate the PI3K signaling pathway, which indicated that apatinib may be a novalnovel and potential drug for LGMS treatments.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004241","title":"Spinocerebellar ataxia type 3 RNA-sequencing study","description":"RNA-Sequencing from human post-mortem Spinocerebellar ataxia type 3 patients. This sequencing experiment was carried out to validate that the transcriptional changes of an Ataxin-3 knock-in mouse model (expressing an expansion of 304 CAG/CAAs either heterozygous or homozygous in the murine Ataxin-3 locus) represent that transcriptional changes seen in the human disease.","abstract":"RNA-Sequencing from human post-mortem Spinocerebellar ataxia type 3 patients. This sequencing experiment was carried out to validate that the transcriptional changes of an Ataxin-3 knock-in mouse model (expressing an expansion of 304 CAG/CAAs either heterozygous or homozygous in the murine Ataxin-3 locus) represent that transcriptional changes seen in the human disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-19T11:07:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004242","title":"Pediatric Low-Grade Glioma RNA and Targeted Sequencing","description":"Pediatric low-grade gliomas (pLGG) are frequently driven by genetic alterations in the RAS/MAPK pathway yet show unexplained variability in their clinical outcome. To address this, we characterized a cohort of &gt;1,000 clinically annotated pLGG. 84% of cases harbored a driver alteration, while those without an identified alteration also often exhibited up-regulation of the RAS/MAPK pathway. pLGG could be broadly classified based on their alteration type. Rearrangement-driven tumors were diagnosed at a younger age, enriched for WHO grade I histology, infrequently progressed, and rarely resulted in death as compared to SNV-driven tumors. Further sub-classification of clinical-molecular correlates stratified pLGG into risk categories. These data highlight the biological and clinical differences between pLGG subtypes and opens avenues for future treatment refinement.","abstract":"Pediatric low-grade gliomas (pLGG) are frequently driven by genetic alterations in the RAS/MAPK pathway yet show unexplained variability in their clinical outcome. To address this, we characterized a cohort of &gt;1,000 clinically annotated pLGG. 84% of cases harbored a driver alteration, while those without an identified alteration also often exhibited up-regulation of the RAS/MAPK pathway. pLGG could be broadly classified based on their alteration type. Rearrangement-driven tumors were diagnosed at a younger age, enriched for WHO grade I histology, infrequently progressed, and rarely resulted in death as compared to SNV-driven tumors. Further sub-classification of clinical-molecular correlates stratified pLGG into risk categories. These data highlight the biological and clinical differences between pLGG subtypes and opens avenues for future treatment refinement.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-19T14:22:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004243","title":"THE GENOMIC LANDSCAPE OF ACTINIC KERATOSIS","description":"Actinic keratoses (AK) are lesions of epidermal keratinocyte dysplasia and are pre-cursor lesions to invasive cutaneous squamous cell carcinoma (cSCC). Identifying the specific genomic alterations driving the progression of normal skin to AK and invasive cSCC is challenging due to the massive, ultraviolet radiation-induced mutational burden characteristic to these lesions. Here, we present the largest whole exome sequencing study to date on AK with matched cSCC and demonstrate that AK and cSCC are almost indistinguishable at the genomic level, in terms of mutational burden, patterns of driver gene mutations and copy number alterations. We identified 44 significantly mutated AK driver genes through our established bioinformatics pipeline and demonstrate these genes are similarly mutated in cSCC. We also identified mutational signature-32 exclusively in AK from patients exposed to azathioprine, providing further, compelling evidence for this drug’s role in keratinocyte carcinogenesis, likely through its blocking of transcription coupled repair. We demonstrated that cSCC had higher levels of intra-sample heterogeneity than AK and that several signaling pathways, including immune-related signaling and TGF-beta signaling were significantly more mutated in cSCC. Integrating our findings with independent gene expression data confirms that dysregulated TGF-beta signaling may represent the critical pathway in the progression from AK to cSCC.","abstract":"Actinic keratoses (AK) are lesions of epidermal keratinocyte dysplasia and are pre-cursor lesions to invasive cutaneous squamous cell carcinoma (cSCC). Identifying the specific genomic alterations driving the progression of normal skin to AK and invasive cSCC is challenging due to the massive, ultraviolet radiation-induced mutational burden characteristic to these lesions. Here, we present the largest whole exome sequencing study to date on AK with matched cSCC and demonstrate that AK and cSCC are almost indistinguishable at the genomic level, in terms of mutational burden, patterns of driver gene mutations and copy number alterations. We identified 44 significantly mutated AK driver genes through our established bioinformatics pipeline and demonstrate these genes are similarly mutated in cSCC. We also identified mutational signature-32 exclusively in AK from patients exposed to azathioprine, providing further, compelling evidence for this drug’s role in keratinocyte carcinogenesis, likely through its blocking of transcription coupled repair. We demonstrated that cSCC had higher levels of intra-sample heterogeneity than AK and that several signaling pathways, including immune-related signaling and TGF-beta signaling were significantly more mutated in cSCC. Integrating our findings with independent gene expression data confirms that dysregulated TGF-beta signaling may represent the critical pathway in the progression from AK to cSCC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-19T17:20:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004244","title":"Transcriptional programming of human alveolar macrophages from COPD patients","description":null,"abstract":"Rationale: Immune cells play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Albeit changes in distribution and cellular functions of major immune cells, such as alveolar macrophages (AMs) and neutrophils have been established, we still do not fully understand their transcriptional reprogramming and contribution to the pathophysiology of COPD. \nObjective: To determine changes in immune cell type distribution, transcriptional reprogramming and lipid metabolism in the bronchoalveolar lavage (BAL) of COPD patients.\nMethods: Multi-color flow cytometry (MCFC) was applied using most current cell-type-determining markers to BAL samples from 29 controls and 30 COPD patients at different clinical stages. Whole transcriptomes and lipidomes were analyzed in sorted CD45+Lin-HLA-DR+CD66b-Autofluoreschencehi AMs. \nMeasurements and Main Results: Neutrophil, group 1 and group 2 innate lymphoid cell (ILC), but not AM absolute cell numbers were significantly increased in COPD patients. Focusing on AMs as the largest cell type in the alveolar space, we defined global transcriptional reprogramming and detected significant changes between controls and COPD patients in genes involved in lipid metabolism. Based on these findings, lipidomic assessment of a total of 249 lipid species in sorted AMs revealed changes of cholesteryl ester (CE), monoacylglycerols (MAG) and phosphatidylcholines (PC) in a stage-dependent manner.\nConclusions: The combination of MCFC, transcriptomics and lipidomics demonstrated changes in cell type distribution, significant transcriptional reprogramming and disease stage-dependent changes of AM lipid metabolism as a novel hallmark of COPD.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004245","title":"Single-cell profiling reveals divergent, globally patterned immune responses in murine skin","description":null,"abstract":"Single-cell profiling reveals divergent, globally patterned immune responses in murine skin","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004246","title":"Representative Sequencing: unbiased sampling of solid tumor tissue","description":null,"abstract":"While thousands of solid tumors have been sequenced to date, a fundamental under-sampling bias is inherent in current methodologies. This is caused by a tissue sample input of fixed dimensions (e.g. 6mm-biopsy), which becomes grossly under-powered as tumor volume scales. Here we demonstrate Representative-Sequencing (Rep-Seq), as a new method to achieve unbiased tumor tissue sampling. Rep-Seq utilizes fixed residual tumor material, which is homogenized and subject to next generation sequencing. Analysis of intra-tumor tumor mutation burden (TMB) variability shows a high level of misclassification with current single biopsy methods, with 20% of lung, and 52% of bladder tumors, having ≥1 biopsy with high-TMB, but low clonal-TMB overall. Misclassification rates by contrast are reduced to 2% (lung) and 4% (bladder) when a more representative sampling methodology is used. Rep-Seq offers an improved sampling protocol for tumor profiling, with significant potential for improved clinical utility and more accurate deconvolution of clonal structure.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004247","title":"HSC_population_dynamics___LEUK4_samples","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-20T12:09:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004248","title":"Whole-exome sequencing of ovarian clear cell carcinoma in clinical outliers","description":"Whole-exome sequencing dataset for the Australian Ovarian Cancer Study (AOCS) and The Jikei University School of Medicine (JIKEI) ovarian clear cell carcinoma (OCCC) clinical outliers project, representing 10 donors. Although OCCC are commonly resistant to platinum based chemotherapy, good clinical outcomes are observed in a subset of patients. Exome sequencing was performed in 10 patients who had either unusually long survival (N=5) or had a very short time to progression (N=5).","abstract":"Whole-exome sequencing dataset for the Australian Ovarian Cancer Study (AOCS) and The Jikei University School of Medicine (JIKEI) ovarian clear cell carcinoma (OCCC) clinical outliers project, representing 10 donors. Although OCCC are commonly resistant to platinum based chemotherapy, good clinical outcomes are observed in a subset of patients. Exome sequencing was performed in 10 patients who had either unusually long survival (N=5) or had a very short time to progression (N=5).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-21T00:53:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004249","title":"Adult granulosa cell tumor WGS data cohort with corresponding reference germline WGS data","description":"Adult granulosa cell tumors (AGCTs) harbor a somatic FOXL2 c.402C&gt;G mutation in ~95% of cases and are mainly surgically removed due to limited systemic treatment effect. In this study, potentially targetable genomic alterations in AGCTs were investigated by whole genome sequencing on 46 tumor samples and matched normal DNA. Copy number variant (CNV) analysis confirmed gain  of chromosome 12 and 14, and loss of 22. Pathogenic TP53 mutations were identified in three patients with highest tumor mutational burden and mitotic activity, defining a high-grade AGCT subgroup. Within-patient tumor comparisons showed 29-80% unique somatic mutations per sample, suggesting tumor heterogeneity. FOXL2-wildtype AGCTs had DICER1, TERT(C228T) and TP53 mutations and similar CNV profiles as FOXL2-mutant tumors. Our study confirms that absence of the FOXL2 c.402C&gt;G mutation does not exclude AGCT diagnosis. The lack of overlapping variants in targetable cancer genes, indicates the need for personalized treatment for AGCT patients ","abstract":"Adult granulosa cell tumors (AGCTs) harbor a somatic FOXL2 c.402C&gt;G mutation in ~95% of cases and are mainly surgically removed due to limited systemic treatment effect. In this study, potentially targetable genomic alterations in AGCTs were investigated by whole genome sequencing on 46 tumor samples and matched normal DNA. Copy number variant (CNV) analysis confirmed gain  of chromosome 12 and 14, and loss of 22. Pathogenic TP53 mutations were identified in three patients with highest tumor mutational burden and mitotic activity, defining a high-grade AGCT subgroup. Within-patient tumor comparisons showed 29-80% unique somatic mutations per sample, suggesting tumor heterogeneity. FOXL2-wildtype AGCTs had DICER1, TERT(C228T) and TP53 mutations and similar CNV profiles as FOXL2-mutant tumors. Our study confirms that absence of the FOXL2 c.402C&gt;G mutation does not exclude AGCT diagnosis. The lack of overlapping variants in targetable cancer genes, indicates the need for personalized treatment for AGCT patients ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-21T10:23:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004250","title":"The landscape of chromothripsis across adult cancer types","description":"Chromothripsis is a recently identified mutational phenomenon, by which a presumably single catastrophic event generates extensive genomic rearrangements of one or a few chromosome(s). Considered as an early event in tumour development, this form of genome instability plays a prominent role in tumour onset. Chromothripsis prevalence might have been underestimated when using low-resolution methods, and pan-cancer studies based on sequencing are rare. We analysed chromothripsis in 28 tumour types covering all major adult cancers (634 tumours, 316 whole-genome and 318 whole-exome sequences). We show that chromothripsis affects a substantial proportion of human cancers, with a prevalence of 49% across all cases. Chromothripsis generates entity-specific genomic alterations driving tumour development, including clinically relevant druggable fusions. Chromothripsis is linked with specific telomere patterns and univocal mutational signatures in distinct tumour entities. Longitudinal analysis of chromothriptic patterns in 24 matched tumour pairs reveals novel insights in the clonal evolution of tumours with chromothripsis. (H021)","abstract":"Chromothripsis is a recently identified mutational phenomenon, by which a presumably single catastrophic event generates extensive genomic rearrangements of one or a few chromosome(s). Considered as an early event in tumour development, this form of genome instability plays a prominent role in tumour onset. Chromothripsis prevalence might have been underestimated when using low-resolution methods, and pan-cancer studies based on sequencing are rare. We analysed chromothripsis in 28 tumour types covering all major adult cancers (634 tumours, 316 whole-genome and 318 whole-exome sequences). We show that chromothripsis affects a substantial proportion of human cancers, with a prevalence of 49% across all cases. Chromothripsis generates entity-specific genomic alterations driving tumour development, including clinically relevant druggable fusions. Chromothripsis is linked with specific telomere patterns and univocal mutational signatures in distinct tumour entities. Longitudinal analysis of chromothriptic patterns in 24 matched tumour pairs reveals novel insights in the clonal evolution of tumours with chromothripsis. (H021)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-21T15:22:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004251","title":"test","description":"test","abstract":"test","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004252","title":"TET-mediated hypermethylation primes SDH-deficient cells for HIF2A-driven mesenchymal transition","description":"Loss-of-function mutations in the SDHB subunit of succinate dehydrogenase predispose to aggressive tumors characterized by pseudohypoxic and hypermethylator phenotypes. The mechanisms leading to DNA hypermethylation and its contribution to SDH-deficient cancers remain undemonstrated. We examined the genome-wide distribution of 5-methylcytosine and 5-hydroxymethylcytosine and their correlation with RNA expression, in SDHB-deficient tumors and murine Sdhb-/- cells. We report that DNA hypermethylation results from TET inhibition. Although it preferentially affects PRC2 targets and known developmental genes, PRC2 activity does not contribute to the DNA hypermethylator phenotype. Besides, we evidence in vitro and in vivo that TET silencing, while recapitulating the methylation profile of Sdhb-/- cells, is not sufficient to drive their EMT-like phenotype, which requires additional HIF2A activation. Altogether, our findings reveal synergistic roles of TET repression and pseudohypoxia in the acquisition of metastatic traits, providing a rationale for targeting HIF2A and DNA methylation in SDH-associated malignancies.","abstract":"Loss-of-function mutations in the SDHB subunit of succinate dehydrogenase predispose to aggressive tumors characterized by pseudohypoxic and hypermethylator phenotypes. The mechanisms leading to DNA hypermethylation and its contribution to SDH-deficient cancers remain undemonstrated. We examined the genome-wide distribution of 5-methylcytosine and 5-hydroxymethylcytosine and their correlation with RNA expression, in SDHB-deficient tumors and murine Sdhb-/- cells. We report that DNA hypermethylation results from TET inhibition. Although it preferentially affects PRC2 targets and known developmental genes, PRC2 activity does not contribute to the DNA hypermethylator phenotype. Besides, we evidence in vitro and in vivo that TET silencing, while recapitulating the methylation profile of Sdhb-/- cells, is not sufficient to drive their EMT-like phenotype, which requires additional HIF2A activation. Altogether, our findings reveal synergistic roles of TET repression and pseudohypoxia in the acquisition of metastatic traits, providing a rationale for targeting HIF2A and DNA methylation in SDH-associated malignancies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004253","title":"A single-cell atlas of human glioma","description":null,"abstract":"Although tumor-propagating cells can be derived from glioblastomas (GBMs) of the proneural and mesenchymal subtypes, a glioma stem-like cell (GSC) of the classical subtype has not been identified. It is unclear if mesenchymal GSCs (mGSCs) and/or proneural GSCs (pGSCs) alone are sufficient to generate the spectrum of cellular heterogeneity observed in GBM. This study sheds light on a long-standing debate regarding lineage relationships among GSCs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004254","title":"Functional_characterisation_of_IBD_genes_using_intestinal_epithelial","description":"Many of the 800 IBD GWAS genes are expressed in epithelial cell types and it is likely that they play a causal role in the pathophysiology of IBD (Huang et al., 2017, GTEx, HCA unpublished data). Here we will develop CRISPR screening approach combined with scRNAseq to examine the effects of repressing up to 30 IBD GWAS genes in iPSC-derived human intestinal organoids (iHO) to explore the role of epithelial barrier dysfunction in the pathophysiology of IBD. iHO are more amenable to screening than mHO, and unlike intestinal epithelial cell line models (e.g. Caco-2), they model the differentiation from stem cell to epithelial cell, and contain all of the major differentiated cell types including, goblet, Paneth, enterocyte and neuroendocrine cells.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Many of the 800 IBD GWAS genes are expressed in epithelial cell types and it is likely that they play a causal role in the pathophysiology of IBD (Huang et al., 2017, GTEx, HCA unpublished data). Here we will develop CRISPR screening approach combined with scRNAseq to examine the effects of repressing up to 30 IBD GWAS genes in iPSC-derived human intestinal organoids (iHO) to explore the role of epithelial barrier dysfunction in the pathophysiology of IBD. iHO are more amenable to screening than mHO, and unlike intestinal epithelial cell line models (e.g. Caco-2), they model the differentiation from stem cell to epithelial cell, and contain all of the major differentiated cell types including, goblet, Paneth, enterocyte and neuroendocrine cells.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004255","title":"Single cell RNA-seq profiling of CD8 T cells from elder adults","description":"Single cell RNA-seq profiling of ~62k purified CD8+ T cell  transcriptomes, from six healthy older adult donors using 10X genomics. Cells from each donor were separated based on their IL-7R protein expression (i.e. CD8+ IL7R+ and CD8+ IL7R- T cells).","abstract":"Single cell RNA-seq profiling of ~62k purified CD8+ T cell  transcriptomes, from six healthy older adult donors using 10X genomics. Cells from each donor were separated based on their IL-7R protein expression (i.e. CD8+ IL7R+ and CD8+ IL7R- T cells).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-24T15:57:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004256","title":"HCA_Female_Reproductive_Adult_WSSS_spatial","description":"Cell atlas of the human placenta\n\nThe Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Cell atlas of the human placenta\n\nThe Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004257","title":"Renal_oncocytomas___WGS","description":"Oncocytomas are a benign kidney cancer. They are often initially misdiagnosed as renal cell carcinomas if no biopsy has taken place prior to definitive surgery. Even after diagnostic biopsy, it is often difficult to differentiate oncocytomas from chromophobe renal cell carcinomas. We plan to examine the genomes and transcriptomes of oncocytomas to understand their relationship to the cell of origin and to better characterised renal cell carcinomas.","abstract":"Here, we seek to describe the genomics and transcriptomics of renal oncocytomas by sequencing 25 such tumour-normal pairs. We document their mutational burden, define driver mutations, demonstrate typical patterns of structural variants, and estimate the cell of origin and cellular composition.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004258","title":"Renal_oncocytomas___RNA_","description":"Oncocytomas are a benign kidney cancer. They are often initially misdiagnosed as renal cell carcinomas if no biopsy has taken place prior to definitive surgery. Even after diagnostic biopsy, it is often difficult to differentiate oncocytomas from chromophobe renal cell carcinomas. We plan to examine the genomes and transcriptomes of oncocytomas to understand their relationship to the cell of origin and to better characterised renal cell carcinomas.","abstract":"Here, we seek to describe the genomics and transcriptomics of renal oncocytomas by sequencing 25 such tumour-normal pairs. We document their mutational burden, define driver mutations, demonstrate typical patterns of structural variants, and estimate the cell of origin and cellular composition.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004259","title":"APCmin_Mice_WT_Old__WG__Novaseq_","description":"Sequencing of LCM-derived microbiopsies from small bowell crypts of OLD mice WT for APC and the MYC superenhancer. Goal is to compare the crypt fission rate between WT mice, APCmin mice, and APCmin + MYC superenhancer Null mice. Crypt fission rate will be assesed by collecting adjacent crypts from multiple regions of the ileum","abstract":"Previous laser-capture microscopy (LCM) studies of human colonic crypts have helped us understand that crypt fission events, whereby a single colonic crypt is split in to two, are extremely rare in healthy tissue. To better understand this process in humans we are using a mouse model of human colon cancer driven by mutation in the APC gene. APCmin mice are short-lived and rapidly develop polyps causing intestinal blockages. However, if the APCmin is combined with a MYC superhancer, these mice live normal lifespans and do not grow polyps. We predict that this rescue is achieved through an increase in the crypt fission rate, allowing for the increased proliferation driven by APCmin to occur laterally, rather than vertically and causing polyps. We aim to use LCM of the small intestinal crypts to measure the crypt fission rate of 3 groups of mice: WT, APCmin, APCmin + MYC superenhancer Null.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004260","title":"APCmin_Mice_WT_Young__WG__Novaseq_","description":"Sequencing of LCM-derived microbiopsies from small bowell crypts of young mice WT for APC and the MYC superenhancer. Goal is to compare the crypt fission rate between WT mice, APCmin mice, and APCmin + MYC superenhancer Null mice. Crypt fission rate will be assesed by collecting adjacent crypts from multiple regions of the ileum.","abstract":"Previous laser-capture microscopy (LCM) studies of human colonic crypts have helped us understand that crypt fission events, whereby a single colonic crypt is split in to two, are extremely rare in healthy tissue. To better understand this process in humans we are using a mouse model of human colon cancer driven by mutation in the APC gene. APCmin mice are short-lived and rapidly develop polyps causing intestinal blockages. However, if the APCmin is combined with a MYC superhancer, these mice live normal lifespans and do not grow polyps. We predict that this rescue is achieved through an increase in the crypt fission rate, allowing for the increased proliferation driven by APCmin to occur laterally, rather than vertically and causing polyps. We aim to use LCM of the small intestinal crypts to measure the crypt fission rate of 3 groups of mice: WT, APCmin, APCmin + MYC superenhancer Null.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004261","title":"APCmin_Mice_APCmin_Young__WG__Novaseq_","description":"Sequencing of LCM-derived microbiopsies from small bowell crypts of young APCmin WT for the MYC superenhancer. Goal is to compare the crypt fission rate between WT mice, APCmin mice, and APCmin + MYC superenhancer Null mice. Crypt fission rate will be assesed by collecting adjacent crypts from multiple regions of the ileum.","abstract":"Previous laser-capture microscopy (LCM) studies of human colonic crypts have helped us understand that crypt fission events, whereby a single colonic crypt is split in to two, are extremely rare in healthy tissue. To better understand this process in humans we are using a mouse model of human colon cancer driven by mutation in the APC gene. APCmin mice are short-lived and rapidly develop polyps causing intestinal blockages. However, if the APCmin is combined with a MYC superhancer, these mice live normal lifespans and do not grow polyps. We predict that this rescue is achieved through an increase in the crypt fission rate, allowing for the increased proliferation driven by APCmin to occur laterally, rather than vertically and causing polyps. We aim to use LCM of the small intestinal crypts to measure the crypt fission rate of 3 groups of mice: WT, APCmin, APCmin + MYC superenhancer Null.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004262","title":"APCmin_Mice_APCmin_MYC_SE_Null_OLD__WG__Novaseq_","description":"Sequencing of LCM-derived microbiopsies from small bowell crypts of OLD APCmin MYC superenhancer null mice. Goal is to compare the crypt fission rate between WT mice, APCmin mice, and APCmin + MYC superenhancer Null mice. Crypt fission rate will be assesed by collecting adjacent crypts from multiple regions of the ileum.","abstract":"Previous laser-capture microscopy (LCM) studies of human colonic crypts have helped us understand that crypt fission events, whereby a single colonic crypt is split in to two, are extremely rare in healthy tissue. To better understand this process in humans we are using a mouse model of human colon cancer driven by mutation in the APC gene. APCmin mice are short-lived and rapidly develop polyps causing intestinal blockages. However, if the APCmin is combined with a MYC superhancer, these mice live normal lifespans and do not grow polyps. We predict that this rescue is achieved through an increase in the crypt fission rate, allowing for the increased proliferation driven by APCmin to occur laterally, rather than vertically and causing polyps. We aim to use LCM of the small intestinal crypts to measure the crypt fission rate of 3 groups of mice: WT, APCmin, APCmin + MYC superenhancer Null.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004263","title":"APCmin_Mice_APCmin_MYC_SE_Null_Young__WG__Novaseq_","description":"Sequencing of LCM-derived microbiopsies from small bowell crypts of young APCmin MYC superenhancer null mice. Goal is to compare the crypt fission rate between WT mice, APCmin mice, and APCmin + MYC superenhancer Null mice. Crypt fission rate will be assesed by collecting adjacent crypts from multiple regions of the ileum.","abstract":"Previous laser-capture microscopy (LCM) studies of human colonic crypts have helped us understand that crypt fission events, whereby a single colonic crypt is split in to two, are extremely rare in healthy tissue. To better understand this process in humans we are using a mouse model of human colon cancer driven by mutation in the APC gene. APCmin mice are short-lived and rapidly develop polyps causing intestinal blockages. However, if the APCmin is combined with a MYC superhancer, these mice live normal lifespans and do not grow polyps. We predict that this rescue is achieved through an increase in the crypt fission rate, allowing for the increased proliferation driven by APCmin to occur laterally, rather than vertically and causing polyps. We aim to use LCM of the small intestinal crypts to measure the crypt fission rate of 3 groups of mice: WT, APCmin, APCmin + MYC superenhancer Null.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004264","title":"Spatial_transcriptome_analysis_of_the_human_heart","description":"Cell Atlas of the human heart\n\nThe aim of this project is to profile human heart on a single-cell level. Cardiac human tissue will be sampled from adult donors and will be processed for 10X single cell and single nuclei RNA sequencing and spatial transcriptomics.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Cell Atlas of the human heart\n\nThe aim of this project is to profile human heart on a single-cell level. Cardiac human tissue will be sampled from adult donors and will be processed for 10X single cell and single nuclei RNA sequencing and spatial transcriptomics.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004265","title":"Spatial_transcriptome_analysis_of_Developmental_Gonads","description":"Cell atlas of germinal cells and gonads\n\nSexual reproduction depends on the fusion of gametes (sperm and eggs) during fertilisation followed by implantation of the resulting embryo in the lining of the womb (the endometrium). Gametes halve their genome in preparation for fertilisation during a specialized cell division known as meiosis. The process by which meiosis is co-ordinated with gamete formation in females is poorly understood, principally because it commences in utero and is not completed until decades later when the mature egg is ovulated and fertilised. \nTo address the many gaps in our knowledge of the development of the germline and reproductive system in humans, we propose to generate a comprehensive cell atlas of the gonads fetal development and human germline. We will combine gene-expression profiling at the single-cell level and atac-seq with new methods of gene-expression detection directly on the tissue to study the cellular environment at an unprecedented resolution and coverage. Information about the expression of the myriad of cells and cell states in reproductive cells will greatly advance our understanding of the development of the female reproductive system and the emergence and maintenance of the female germline in humans. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Cell atlas of germinal cells and gonads\n\nSexual reproduction depends on the fusion of gametes (sperm and eggs) during fertilisation followed by implantation of the resulting embryo in the lining of the womb (the endometrium). Gametes halve their genome in preparation for fertilisation during a specialized cell division known as meiosis. The process by which meiosis is co-ordinated with gamete formation in females is poorly understood, principally because it commences in utero and is not completed until decades later when the mature egg is ovulated and fertilised. \nTo address the many gaps in our knowledge of the development of the germline and reproductive system in humans, we propose to generate a comprehensive cell atlas of the gonads fetal development and human germline. We will combine gene-expression profiling at the single-cell level and atac-seq with new methods of gene-expression detection directly on the tissue to study the cellular environment at an unprecedented resolution and coverage. Information about the expression of the myriad of cells and cell states in reproductive cells will greatly advance our understanding of the development of the female reproductive system and the emergence and maintenance of the female germline in humans. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004266","title":"Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma","description":"Recent advances in throughput and accuracy mean that the Oxford Nanopore Technologies (ONT) PromethION platform is a now a viable solution for WGS. New bioinformatic methods have been developed to take advantage of this long read data, however much of the validation of these tools has focussed on calling germline variants (both SNVs and structural variants). Somatic variants are outnumbered many-fold by germline variants and their detection is further complicated due to their frequency varying depending on tumour purity/subclonality. Here, we evaluate the extent to which Nanopore WGS enables genome-wide detection and analysis of somatic variation. We do this through sequencing tumour and germline genomes for a patient with diffuse B-cell lymphoma. We examine the capability of currently available tools for calling somatic variants in ONT data by comparing the data with results from 150bp short-read sequencing of the same samples. We then conduct a detailed analysis of the performance of multiple long-read mappers and structural variant callers for calling large, somatic structural variants (SVs) in ONT data. Our protocol achieved yields of up to 96 mapped Gb per PromethION flow cell with average read lengths of ~5kb. Calling germline SNVs from these data achieved good specificity and sensitivity. However, results of somatic SNV calling highlight the need for the development of specialized joint calling algorithms. Our analysis of structural variants shows that the comparative performance of different tools varies significantly between SV types, and suggest long reads are especially advantageous for calling large somatic deletions and duplications. Finally, we highlight the utility of long reads for phasing clinically relevant variants by using the ONT data to confirm that a somatic 1.6Mb deletion and a p.(Arg249Met) mutation involving TP53 are oriented in trans.","abstract":"Recent advances in throughput and accuracy mean that the Oxford Nanopore Technologies (ONT) PromethION platform is a now a viable solution for WGS. New bioinformatic methods have been developed to take advantage of this long read data, however much of the validation of these tools has focussed on calling germline variants (both SNVs and structural variants). Somatic variants are outnumbered many-fold by germline variants and their detection is further complicated due to their frequency varying depending on tumour purity/subclonality. Here, we evaluate the extent to which Nanopore WGS enables genome-wide detection and analysis of somatic variation. We do this through sequencing tumour and germline genomes for a patient with diffuse B-cell lymphoma. We examine the capability of currently available tools for calling somatic variants in ONT data by comparing the data with results from 150bp short-read sequencing of the same samples. We then conduct a detailed analysis of the performance of multiple long-read mappers and structural variant callers for calling large, somatic structural variants (SVs) in ONT data. Our protocol achieved yields of up to 96 mapped Gb per PromethION flow cell with average read lengths of ~5kb. Calling germline SNVs from these data achieved good specificity and sensitivity. However, results of somatic SNV calling highlight the need for the development of specialized joint calling algorithms. Our analysis of structural variants shows that the comparative performance of different tools varies significantly between SV types, and suggest long reads are especially advantageous for calling large somatic deletions and duplications. Finally, we highlight the utility of long reads for phasing clinically relevant variants by using the ONT data to confirm that a somatic 1.6Mb deletion and a p.(Arg249Met) mutation involving TP53 are oriented in trans.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-27T15:17:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004267","title":"Resequencing (MIPS) of candidate genes for Keratoconus (2020)","description":"In this study, we selected 34 candidate genes for KC based on previous Whole Exome Sequencing (WES) and the literature, and resequenced them in 745 KC patients and 810 ethnically matched controls.  Data analysis was performed using the single variant association test as well as gene-based mutation burden and variance components tests. \nIn our study, we detected enrichment of genetic variation across multiple gene-based tests for the genes COL2A1, COL5A1, TNXB, ZEB1 and ZNF469. The top hit in the Fisher’s exact test was obtained for a common variant in the COL12A1 gene. Interestingly, COL5A1, TNXB, ZNF469 and COL12A1 are all known Ehlers-Danlos Syndrome (EDS) genes. Though the co-occurrence of KC and EDS has been reported previously, this study is the first to demonstrate a consistent role of genetic variants in EDS genes in the etiology of KC. In conclusion, our data show a shared genetic etiology between KC and EDS, and clearly confirm the currently disputed role of ZNF469 in disease susceptibility for KC. Besides the role for EDS genes, we also confirm the previously reported involvement of genetic variation in ZEB1 in KC.","abstract":"In this study, we selected 34 candidate genes for KC based on previous Whole Exome Sequencing (WES) and the literature, and resequenced them in 745 KC patients and 810 ethnically matched controls.  Data analysis was performed using the single variant association test as well as gene-based mutation burden and variance components tests. \nIn our study, we detected enrichment of genetic variation across multiple gene-based tests for the genes COL2A1, COL5A1, TNXB, ZEB1 and ZNF469. The top hit in the Fisher’s exact test was obtained for a common variant in the COL12A1 gene. Interestingly, COL5A1, TNXB, ZNF469 and COL12A1 are all known Ehlers-Danlos Syndrome (EDS) genes. Though the co-occurrence of KC and EDS has been reported previously, this study is the first to demonstrate a consistent role of genetic variants in EDS genes in the etiology of KC. In conclusion, our data show a shared genetic etiology between KC and EDS, and clearly confirm the currently disputed role of ZNF469 in disease susceptibility for KC. Besides the role for EDS genes, we also confirm the previously reported involvement of genetic variation in ZEB1 in KC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-27T15:27:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004268","title":"Bone metastatic biopsies of breast cancer patients progressing on endocrine therapies.","description":null,"abstract":"A significant proportion of patients with ER positive breast cancers (BC) develop resistance to endocrine treatments (ET) and relapse with metastatic disease. Bone is the most common metastatic site in ER+ patients, however bone metastases are technically challenging to biopsy and analyse. Difficulties concern both tumour tissue acquisition and techniques for analysis and RNA extractions. Patient-derived xenografts (PDX) of BC bone metastases have not been reported yet. For the first time we established PDX models from bone metastatic biopsies of patients progressing on ET and treated by vertebroplasty. PDX models were analysed at genomiclevel and compared to patient’s early primary tumours to identify new therapeutic targets associated with endocrine resistance in the metastatic setting.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-28T10:20:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004269","title":"Understanding_the_genetics_of_human_urinary_bladder_TCC","description":"Bladder cancer is the most common cancer of urinary system, with urothelial carcinoma (UC)/transitional cell carcinoma (TCC) accounting for 90% of the cases in Europe and USA. ~25% of patients have muscle invasive bladder cancer (MIBC), many of which either present with or later develop metastatic disease. With the contemporary chemotherapy regimens, the current 5-years survival rate is only 15%. Thus better treatments are needed.\n        Bladder cancer in companion animals (cats and dogs) is usually UC/TCC. ~20% of dogs with bladder cancer have metastases at the time of diagnosis, and dogs with UC/TCC of the bladder only live for 6-12 months despite treatment. The epidemiological and histological similarities between UC/TCC in companion animals and humans, suggest they may be relevant models of the disease. Bladder cancer in cows is generally rare, however in parts of the world where cattle graze on bracken fern, tumours of the bladder are common (associated with chronic enzootic haematuria), due to the presence of the carcinogen ptaquiloside in the ferns. Given that exposure to chemicals is one of the risk factors for bladder cancer in humans, UC/TCC in cows may also represent a relevant model.\n        We propose to whole-exome sequence tumor-germline pairs of primary (invasive/infiltrating) and metastatic urothelial/transitional cell carcinoma (UC/TCC) of the bladder from humans, as well as dogs, cats and cows. Our goal is to establish the mutational landscape of UC/TCC in these animals and to perform cross-species comparison with human bladder cancer. This will allow us to assess how genetically similar spontaneous UC/TCC in these animals is to the human disease and whether they represent relevant models. If so, it will help us to rationally apply emerging targeted therapies for UC/TCC across several species, in line with the One Health Initiative.","abstract":"Bladder cancer is the most common cancer of urinary system, with urothelial carcinoma (UC)/transitional cell carcinoma (TCC) accounting for 90% of the cases in Europe and USA. ~25% of patients have muscle invasive bladder cancer (MIBC), many of which either present with or later develop metastatic disease. With the contemporary chemotherapy regimens, the current 5-years survival rate is only 15%. Thus better treatments are needed.\n        Bladder cancer in companion animals (cats and dogs) is usually UC/TCC. ~20% of dogs with bladder cancer have metastases at the time of diagnosis, and dogs with UC/TCC of the bladder only live for 6-12 months despite treatment. The epidemiological and histological similarities between UC/TCC in companion animals and humans, suggest they may be relevant models of the disease. Bladder cancer in cows is generally rare, however in parts of the world where cattle graze on bracken fern, tumours of the bladder are common (associated with chronic enzootic haematuria), due to the presence of the carcinogen ptaquiloside in the ferns. Given that exposure to chemicals is one of the risk factors for bladder cancer in humans, UC/TCC in cows may also represent a relevant model.\n        We propose to whole-exome sequence tumor-germline pairs of primary (invasive/infiltrating) and metastatic urothelial/transitional cell carcinoma (UC/TCC) of the bladder from humans, as well as dogs, cats and cows. Our goal is to establish the mutational landscape of UC/TCC in these animals and to perform cross-species comparison with human bladder cancer. This will allow us to assess how genetically similar spontaneous UC/TCC in these animals is to the human disease and whether they represent relevant models. If so, it will help us to rationally apply emerging targeted therapies for UC/TCC across several species, in line with the One Health Initiative.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004270","title":"CHD8 RNAseq","description":null,"abstract":"This study aims to conduct a landscape analysis of transcriptome from a patient with CHD8 deletion. RNAseq was conducted on a patient and normal sibling, each sample in triplicate.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-28T12:44:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004271","title":"Genome-wide study of the effect of blood collection tubes on the cell-free DNA methylome","description":"Background The methylation pattern of cfDNA, isolated from liquid biopsies, is gaining substantial interest for diagnosis and monitoring of diseases. We have evaluated the impact of type of blood collection tube and time delay between blood draw and plasma preparation on bisulfite-based cfDNA methylation profiling.\n\nMethods 15 tubes of blood were drawn from three healthy volunteer subjects (BD Vacutainer K2E EDTA spray tubes, Streck Cell-Free DNA BCT tubes, PAXgene Blood ccfDNA tubes, Roche Cell-Free DNA Collection tubes and Biomatrica LBgard blood tubes in triplicate). Samples were either immediately processed or stored at room temperature for 24 or 72 hours before plasma preparation. DNA fragment size was evaluated by capillary electrophoresis. Reduced representation bisulfite sequencing was performed on the cell-free DNA isolated from these plasma samples. We evaluated the impact of blood tube and time delay on several quality control metrics.\n\nResults All preservation tubes performed similar on the quality metrics that were evaluated. Furthermore, a considerable increase in cfDNA concentration and the fraction of it derived from NK cells was observed after a 72-hour time delay in EDTA tubes.\n\nConclusion The methylation pattern of cfDNA is robust and reproducible in between the different preservation tubes. EDTA tubes processed as soon as possible, preferably within 24 hours, are the most cost effective. If immediate processing is not possible, preservation tubes are valid alternatives.","abstract":"Background The methylation pattern of cfDNA, isolated from liquid biopsies, is gaining substantial interest for diagnosis and monitoring of diseases. We have evaluated the impact of type of blood collection tube and time delay between blood draw and plasma preparation on bisulfite-based cfDNA methylation profiling.\n\nMethods 15 tubes of blood were drawn from three healthy volunteer subjects (BD Vacutainer K2E EDTA spray tubes, Streck Cell-Free DNA BCT tubes, PAXgene Blood ccfDNA tubes, Roche Cell-Free DNA Collection tubes and Biomatrica LBgard blood tubes in triplicate). Samples were either immediately processed or stored at room temperature for 24 or 72 hours before plasma preparation. DNA fragment size was evaluated by capillary electrophoresis. Reduced representation bisulfite sequencing was performed on the cell-free DNA isolated from these plasma samples. We evaluated the impact of blood tube and time delay on several quality control metrics.\n\nResults All preservation tubes performed similar on the quality metrics that were evaluated. Furthermore, a considerable increase in cfDNA concentration and the fraction of it derived from NK cells was observed after a 72-hour time delay in EDTA tubes.\n\nConclusion The methylation pattern of cfDNA is robust and reproducible in between the different preservation tubes. EDTA tubes processed as soon as possible, preferably within 24 hours, are the most cost effective. If immediate processing is not possible, preservation tubes are valid alternatives.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-28T13:28:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004272","title":"Genetic characterization of a Unique Neuroendocrine Transdifferentiation Prostate Circulating Tumor Cell - Derived eXplant (CDX) Model","description":null,"abstract":"Transformation of castration-resistant prostate cancer (CRPC) into an aggressive neuroendocrine disease (CRPC-NE) represents a major clinical challenge and experimental models are lacking. A CTC-derived eXplant (CDX) and a CDX-derived cell line were established using circulating tumor cells (CTCs) obtained by diagnostic leukapheresis from a CRPC patient resistant to enzalutamide. The CDX and the derived-cell line conserved 16% of primary tumor (PT) and 56% of CTC mutations, as well as 83% of PT copy-number aberrations including clonal TMPRSS2-ERG fusion and NKX3.1 loss. Both harbored an androgen receptor-null neuroendocrine phenotype, TP53, PTEN and RB1 loss. While PTEN and RB1 loss were acquired in CTCs, evolutionary analysis suggested that a PT subclone harboring TP53 loss was the driver of the metastatic event leading to the CDX. This CDX model provides insights on the sequential acquisition of key drivers of neuroendocrine transdifferentiation and offers a unique tool for effective drug screening in CRPC-NE management.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-28T14:55:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004273","title":"RUNX1 mutated families show phenotype heterogeneity and a somatic mutation profile unique to germline predisposed AML","description":"We present the clinical phenotypes and genetic mutations detected in 10 novel RUNX1 mutated FPD-MM families. Genomic analyses on these families detected two partial gene deletions, three novel mutations and five recurrent mutations as the germline RUNX1 alterations leading to FPD-MM. On 15 individuals, across the 10 families, we performed additional whole exome or myeloid panel sequencing on blood or bone marrow to determine somatic mutations that co-exist  with the germline RUNX1 mutation in tumour and pre-leukaemic states.","abstract":"We present the clinical phenotypes and genetic mutations detected in 10 novel RUNX1 mutated FPD-MM families. Genomic analyses on these families detected two partial gene deletions, three novel mutations and five recurrent mutations as the germline RUNX1 alterations leading to FPD-MM. On 15 individuals, across the 10 families, we performed additional whole exome or myeloid panel sequencing on blood or bone marrow to determine somatic mutations that co-exist  with the germline RUNX1 mutation in tumour and pre-leukaemic states.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-02-29T06:38:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004274","title":"Mutation signatures in melanocytic nevi reveal characteristics of defective DNA repair","description":"Nevi are common benign melanocytic neoplasms that can be found on any skin location and share many of the genomic hallmarks of melanoma. In our recent report involving whole-exome sequencing of acquired nevi (Stark et al., 2018), ultra-violet radiation (UVR) related somatic mutation signatures (“signature 7”) (Alexandrov et al., 2013) were frequently observed in all lesions that were located on sun-exposed sites. In the study presented herein, we sought to investigate whether an independent Spanish cohort (Valencia, Spain) of minimally sun exposed nevi had genomic features consistent with our previous findings.","abstract":"Nevi are common benign melanocytic neoplasms that can be found on any skin location and share many of the genomic hallmarks of melanoma. In our recent report involving whole-exome sequencing of acquired nevi (Stark et al., 2018), ultra-violet radiation (UVR) related somatic mutation signatures (“signature 7”) (Alexandrov et al., 2013) were frequently observed in all lesions that were located on sun-exposed sites. In the study presented herein, we sought to investigate whether an independent Spanish cohort (Valencia, Spain) of minimally sun exposed nevi had genomic features consistent with our previous findings.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-02T00:44:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004275","title":"Multiplexed quantification of four neuroblastoma DNA targets in a single droplet digital PCR reaction","description":"Evaluation of quadruplex ddPCR-based copy number assessment in blood plasma samples paired with genomic DNA from the corresponding primary neuroblastoma from three patients and comparison with copy numbers determined by duplex and triplex ddPCR and re-analyzed from whole-exome sequencing (WES) data.","abstract":"Evaluation of quadruplex ddPCR-based copy number assessment in blood plasma samples paired with genomic DNA from the corresponding primary neuroblastoma from three patients and comparison with copy numbers determined by duplex and triplex ddPCR and re-analyzed from whole-exome sequencing (WES) data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-02T13:40:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004276","title":"Longitudinal therapy monitoring of ALK-positive non-small cell lung cancer (copy number, cell-free DNA)","description":"Clinical courses of non-small cell lung cancer patients with ALK rearrangements (ALK+ NSCLC) vary widely. We analyzed 271 longitudinal plasma samples from 73 patients with advanced ALK+ NSCLC treated with ALK tyrosine kinase inhibitors by combined hybrid-capture-based targeted sequencing (average 4,100x coverage) for mutation analysis and shallow whole genome sequencing (0.5x coverage) for global copy number profiling from cfDNA.","abstract":"Clinical courses of non-small cell lung cancer patients with ALK rearrangements (ALK+ NSCLC) vary widely. We analyzed 271 longitudinal plasma samples from 73 patients with advanced ALK+ NSCLC treated with ALK tyrosine kinase inhibitors by combined hybrid-capture-based targeted sequencing (average 4,100x coverage) for mutation analysis and shallow whole genome sequencing (0.5x coverage) for global copy number profiling from cfDNA.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-02T14:08:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004277","title":"Germline SDHB-inactivating mutation in gastric spindle cell sarcoma (HIPO-021)","description":"Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. Inactivating mutations or epigenetic deregulation of succinate dehydrogenase complex (SDH) genes are considered defining features of a subset of GIST occurring in the stomach. Based on comprehensive molecular profiling and biochemical analysis within a precision oncology program, we identified hallmarks of SDH deficiency (germline SDHB-inactivating mutation accompanied by somatic loss of heterozygosity, lack of SDHB expression, global DNA hypermethylation, and elevated succinate/fumarate ratio) in a 40-year-old woman with undifferentiated gastric spindle cell sarcoma that did not meet the diagnostic criteria for other mesenchymal tumors of the stomach, including GIST. These data reveal that the loss of SDH function can be involved in the pathogenesis of non-GIST sarcoma of the gastrointestinal tract.","abstract":"Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. Inactivating mutations or epigenetic deregulation of succinate dehydrogenase complex (SDH) genes are considered defining features of a subset of GIST occurring in the stomach. Based on comprehensive molecular profiling and biochemical analysis within a precision oncology program, we identified hallmarks of SDH deficiency (germline SDHB-inactivating mutation accompanied by somatic loss of heterozygosity, lack of SDHB expression, global DNA hypermethylation, and elevated succinate/fumarate ratio) in a 40-year-old woman with undifferentiated gastric spindle cell sarcoma that did not meet the diagnostic criteria for other mesenchymal tumors of the stomach, including GIST. These data reveal that the loss of SDH function can be involved in the pathogenesis of non-GIST sarcoma of the gastrointestinal tract.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-02T15:18:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004278","title":"ATAC-Seq data from ExVivo and Stimulated human naïve (TN), stem cell memory (TSCM), memory exhausted (TMEX) and effector memory (TEM) CD8+ T cells","description":null,"abstract":"Stem-like properties are major determinants of long-lived T cell immunity in physiology and of durable responses in the treatment of cancer, and have been attributed to multiple subsets of CD8+ T cells. It is therefore unclear whether a specific subpopulation retains superior functional capacity. By high-dimensional single cell profiling of human memory T cells, we have identified a subpopulation of LEF1hi CCR7+ T cells lacking the inhibitory receptors PD1 and TIGIT with superior effector functional capacity, long-term repopulation ability, and resistance to exhaustion. Albeit retaining substantial memory traits, the CCR7+ PD1+ TIGIT+ counterpart was largely distinct at the clonal level and displayed features of dysfunctional/exhausted T cells at the transcriptomic and epigenomic level readily ex vivo, that were inherited in their progeny following immune activation and multiple rounds of cell divisions. Thus, we reveal the existence of parallel programs of functional versus dysfunctional memory T cell differentiation in humans featuring their own progenitors, and with important consequences for vaccination and adoptive T cell therapies.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004279","title":"Ultra-deep targeted sequencing for studying the accumulation of somatic mutations in cancer-free human skin","description":null,"abstract":"This study focused on delineating how somatic mutations accumulate in sun-exposed normal skin taking into account several phenotypic data (age, skin phototype...) as well as sun exposure habits. A panel of 46 cancer genes was deeply sequenced in normal skin biopsies from a large cohort of 127 healthy donors. Sequencing of paired-end 100bp reads was performed on an Illumina HiSeq 2000 machine. Paired-end reads were aligned to the reference human genome (GRCh37d5)","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004280","title":"ImmunoAgeing_Colonies_WGS","description":"Aim to determine age at acquisition of clonal haematopoiesis mutations, clonal architecture, and dynamics of clonal expansions.","abstract":"Aim to determine age at acquisition of clonal haematopoiesis mutations, clonal architecture, and dynamics of clonal expansions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-03T09:48:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004281","title":"Spatial_transcriptome_analysis_of_Paediatric_Thymus","description":"Cell atlas of Paediatric Thymus\n\nCell atlas of Paediatric Thymus - The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through; genetic and genomic analysis, expression analysis, non-identifiable video imaging and cell line and organoid production, as well as, computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequently validate these findings in situ using spatial genomic and imaging technologies e.g. immunohistochemistry, RNAscope, in situ sequencing and spatial transcriptomic analyses.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Cell atlas of Paediatric Thymus\n\nCell atlas of Paediatric Thymus - The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through; genetic and genomic analysis, expression analysis, non-identifiable video imaging and cell line and organoid production, as well as, computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequently validate these findings in situ using spatial genomic and imaging technologies e.g. immunohistochemistry, RNAscope, in situ sequencing and spatial transcriptomic analyses.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-03T10:49:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004282","title":"Successful BRAF/MEK-inhibition in a young patient with BRAF V600E-mutated extrapancreatic acinar cell carcinoma (HIPO-021)","description":"Pancreatic acinar cell carcinoma (PAC) is a rare disease with a poor prognosis. Treatment options for metastatic PAC are limited and often follow chemotherapeutic regimens for pancreatic ductal adenocarcinoma. Although recurrent genomic alterations, such as BRAF fusions and defects in genes involved in homologous recombination DNA repair, have been described in PAC, data on the clinical efficacy of molecularly guided, targeted treatment are scarce. Here we describe the case of a 27-yr-old patient with BRAF V600E-mutated PAC who was successfully treated with a combination of BRAF and MEK inhibitors. The patient presented to our clinic with abdominal pain and weight loss. Imaging showed extensive retroperitoneal disease as well as mediastinal lymphadenopathy. Because of elevated alpha-fetoprotein (AFP) levels and inconclusive histologic findings, a germ cell tumor was suspected; however, PEI chemotherapy was unsuccessful. A repeat biopsy yielded the diagnosis of PAC and treatment with FOLFIRINOX was initiated. Comprehensive molecular profiling within the MASTER (Molecularly Aided Stratification for Tumor Eradication Research) precision oncology program revealed a somatic BRAF V600E mutation and a germline PALB2 stop-gain mutation. Therapy was therefore switched to BRAF/MEK inhibition, resulting in almost complete remission and disease control for 12 mo and a remarkable improvement in the patient's general condition. These results indicate that BRAF alterations are a valid therapeutic target in PAC that should be routinely assessed in this patient population.","abstract":"Pancreatic acinar cell carcinoma (PAC) is a rare disease with a poor prognosis. Treatment options for metastatic PAC are limited and often follow chemotherapeutic regimens for pancreatic ductal adenocarcinoma. Although recurrent genomic alterations, such as BRAF fusions and defects in genes involved in homologous recombination DNA repair, have been described in PAC, data on the clinical efficacy of molecularly guided, targeted treatment are scarce. Here we describe the case of a 27-yr-old patient with BRAF V600E-mutated PAC who was successfully treated with a combination of BRAF and MEK inhibitors. The patient presented to our clinic with abdominal pain and weight loss. Imaging showed extensive retroperitoneal disease as well as mediastinal lymphadenopathy. Because of elevated alpha-fetoprotein (AFP) levels and inconclusive histologic findings, a germ cell tumor was suspected; however, PEI chemotherapy was unsuccessful. A repeat biopsy yielded the diagnosis of PAC and treatment with FOLFIRINOX was initiated. Comprehensive molecular profiling within the MASTER (Molecularly Aided Stratification for Tumor Eradication Research) precision oncology program revealed a somatic BRAF V600E mutation and a germline PALB2 stop-gain mutation. Therapy was therefore switched to BRAF/MEK inhibition, resulting in almost complete remission and disease control for 12 mo and a remarkable improvement in the patient's general condition. These results indicate that BRAF alterations are a valid therapeutic target in PAC that should be routinely assessed in this patient population.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-03T11:39:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004283","title":"Ensemble learning for classifying single-cell data and projection across reference atlases","description":"Single-cell data are being generated at an accelerating pace.How best to project data across single-cell atlases is an open problem. We developed a boosted learner that overcomes the greatest challenge with status quo classifiers: low sensitivity, especially when dealing with rare cell types.","abstract":"Single-cell data are being generated at an accelerating pace.How best to project data across single-cell atlases is an open problem. We developed a boosted learner that overcomes the greatest challenge with status quo classifiers: low sensitivity, especially when dealing with rare cell types.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-03T17:59:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004284","title":"The impact of urbanization and diet on innate immune responses in healthy Tanzanians","description":null,"abstract":"Urban versus rural residency in northern Tanzania is associated with a pro-inflammatory phenotype which is explained by differences in food- and endogenous-derived metabolites with immune properties.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-03T18:50:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004285","title":"The double-hit signature identifies double-hit diffuse large B-cell lymphoma with genetic events cryptic to FISH​","description":"High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/THs) include a group of diffuse large B-cell lymphomas (DLBCLs) with inferior outcomes after standard chemoimmunotherapy. We recently described a gene expression signature that identifies 27% of germinal center B-cell DLBCLs (GCB-DLBCLs) as having a double-hit-like expression pattern (DHITsig) and inferior outcomes; however, only half of these cases have both MYC and BCL2 translocations identifiable using standard breakapart fluorescence in situ hybridization (FISH). Here, 20 DHITsig+ GCB-DLBCLs apparently lacking MYC and/or BCL2 rearrangements underwent whole-genome sequencing. This revealed 6 tumors with MYC or BCL2 rearrangements that were cryptic to breakapart FISH. Copy-number analysis identified 3 tumors with MYC and 6 tumors with MIR17HG gains or amplifications, both of which may contribute to dysregulation of MYC and its downstream pathways. Focal deletions of the PVT1 promoter were observed exclusively among DHITsig+ tumors lacking MYC translocations; this may also contribute to MYC overexpression. These results highlight that FISH fails to identify all HGBL-DH/THs, while revealing a range of other genetic mechanisms potentially underlying MYC dysregulation in DHITsig+ DLBCL, suggesting that gene expression profiling is more sensitive for identifying the biology underlying poor outcomes in GCB-DLBCL.","abstract":"High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/THs) include a group of diffuse large B-cell lymphomas (DLBCLs) with inferior outcomes after standard chemoimmunotherapy. We recently described a gene expression signature that identifies 27% of germinal center B-cell DLBCLs (GCB-DLBCLs) as having a double-hit-like expression pattern (DHITsig) and inferior outcomes; however, only half of these cases have both MYC and BCL2 translocations identifiable using standard breakapart fluorescence in situ hybridization (FISH). Here, 20 DHITsig+ GCB-DLBCLs apparently lacking MYC and/or BCL2 rearrangements underwent whole-genome sequencing. This revealed 6 tumors with MYC or BCL2 rearrangements that were cryptic to breakapart FISH. Copy-number analysis identified 3 tumors with MYC and 6 tumors with MIR17HG gains or amplifications, both of which may contribute to dysregulation of MYC and its downstream pathways. Focal deletions of the PVT1 promoter were observed exclusively among DHITsig+ tumors lacking MYC translocations; this may also contribute to MYC overexpression. These results highlight that FISH fails to identify all HGBL-DH/THs, while revealing a range of other genetic mechanisms potentially underlying MYC dysregulation in DHITsig+ DLBCL, suggesting that gene expression profiling is more sensitive for identifying the biology underlying poor outcomes in GCB-DLBCL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-03T20:49:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004286","title":"Total RNAseq in the sporadic ALS and healthy control motor cortex","description":"Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of upper and lower motor neurons leading to progressive muscle weakness, wasting and paralysis that result in death within a few years from disease onset.\nIn order to characterize RNA alterations in ALS, total RNAseq was performed in the ALS motor cortex, which is an early and vulnerable region in ALS.","abstract":"Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of upper and lower motor neurons leading to progressive muscle weakness, wasting and paralysis that result in death within a few years from disease onset.\nIn order to characterize RNA alterations in ALS, total RNAseq was performed in the ALS motor cortex, which is an early and vulnerable region in ALS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-04T10:16:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004287","title":"Roma Sequencing Study","description":"Present day Roma genome were shaped by the extensive inbreeding and admixture during their Diaspora. Here, we shed light on the Roma demographic history by analyzing the whole genome sequence of 46 Roma individuals pertaining to four migrant groups in six European countries. The strong reduction in effective population size (~44%), that occurred around 2kya, was not masked by the subsequent high admixture in Middle Eastern and European countries.","abstract":"Present day Roma genome were shaped by the extensive inbreeding and admixture during their Diaspora. Here, we shed light on the Roma demographic history by analyzing the whole genome sequence of 46 Roma individuals pertaining to four migrant groups in six European countries. The strong reduction in effective population size (~44%), that occurred around 2kya, was not masked by the subsequent high admixture in Middle Eastern and European countries.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-04T13:49:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004288","title":"Circulating tumor cells for comprehensive and multiregional non-invasive genetic characterization of multiple myeloma","description":null,"abstract":"Multiple myeloma (MM) patients undergo repetitive bone marrow (BM) aspirates for genetic characterization. Circulating tumor cells (CTCs) are detectable in peripheral blood of virtually all MM cases and are prognostic, but their applicability for non-invasive screening has been poorly investigated. Here, we used next-generation flow cytometry to isolate matched CTCs and BM tumor cells from 42 patients and compare their genetic profile. In 8 cases, tumor cells from extramedullary plasmacytomas were also sorted and whole-exome sequencing performed in the three spatially-distributed clones. Noteworthy, ≥84% mutations present in BM and extramedullary clones were detectable in CTCs. Concordance between BM tumor cells and CTCs was high for chromosome arm-level copy-number alterations (≥94%) though not for translocations (43%). All high-risk genetic abnormalities except one t(4;14) were detected in CTCs whenever present in BM tumor cells. Altogether, these results support CTCs for non-invasive risk-stratification of MM patients based on their numbers and genetic profile.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-04T14:40:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004289","title":"Coding and non-coding drivers of mantle cell lymphoma identified through exome and genome sequencing","description":"Mantle cell lymphoma (MCL) is an uncommon B-cell non-Hodgkin lymphoma (NHL) that is incurable with standard therapies. The genetic drivers of this cancer have not been firmly established and the features that contribute to differences in clinical course remain limited. To extend our understanding of the biological pathways involved in this malignancy, we performed a large-scale genomic analysis of MCL using data from 51 exomes and 34 genomes alongside previously published exome cohorts. To confirm our findings, we re-sequenced the genes identified in the exome cohort in 191 MCL tumors, each having clinical follow-up data. We confirmed the prognostic association of TP53 and NOTCH1 mutations. Our sequencing revealed novel recurrent non-coding mutations surrounding a single exon of the HNRNPH1 gene. In RNA-seq data from 103 of these cases, MCL tumors with these mutations had a distinct imbalance of HNRNPH1 isoforms. This altered splicing of HNRNPH1 was associated with inferior outcomes in MCL and showed a significant increase in protein expression by immunohistochemistry. We describe a functional role for these recurrent non-coding mutations in disrupting an auto-regulatory feedback mechanism, thereby deregulating HNRNPH1 protein expression. Taken together, these data strongly implicate a role for aberrant regulation of mRNA processing in MCL pathobiology.","abstract":"Mantle cell lymphoma (MCL) is an uncommon B-cell non-Hodgkin lymphoma (NHL) that is incurable with standard therapies. The genetic drivers of this cancer have not been firmly established and the features that contribute to differences in clinical course remain limited. To extend our understanding of the biological pathways involved in this malignancy, we performed a large-scale genomic analysis of MCL using data from 51 exomes and 34 genomes alongside previously published exome cohorts. To confirm our findings, we re-sequenced the genes identified in the exome cohort in 191 MCL tumors, each having clinical follow-up data. We confirmed the prognostic association of TP53 and NOTCH1 mutations. Our sequencing revealed novel recurrent non-coding mutations surrounding a single exon of the HNRNPH1 gene. In RNA-seq data from 103 of these cases, MCL tumors with these mutations had a distinct imbalance of HNRNPH1 isoforms. This altered splicing of HNRNPH1 was associated with inferior outcomes in MCL and showed a significant increase in protein expression by immunohistochemistry. We describe a functional role for these recurrent non-coding mutations in disrupting an auto-regulatory feedback mechanism, thereby deregulating HNRNPH1 protein expression. Taken together, these data strongly implicate a role for aberrant regulation of mRNA processing in MCL pathobiology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-04T23:25:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004290","title":"Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell RCC -- CA209-009","description":"Immune checkpoint inhibitors targeting the PD-1 pathway have transformed the management of many advanced malignancies, including clear cell renal cell carcinoma (ccRCC), but the drivers and resistors of PD-1 response remain incompletely elucidated. Here, we analyzed 592 tumors collected from advanced ccRCC patients enrolled in prospective clinical trials of treatment with PD-1 blockade (or mTOR inhibition as control arm) by whole-exome and RNA-sequencing, integrated with immunofluorescence analysis, to define the somatic alteration landscape of late-stage ccRCC and to uncover the immunogenomic determinants of therapeutic response. While conventional genomic markers (tumor mutation burden, neoantigen load) and degree of CD8+ T cell infiltration were not associated with clinical response, we discovered numerous chromosomal alterations in advanced ccRCC associated with response or resistance to PD-1 blockade. These advanced tumors were highly CD8+ T cell infiltrated, with only 22% and 5% with an immune desert and immune excluded phenotype, respectively. Our analysis revealed that CD8+ infiltrated tumors are depleted of favorable PBRM1 mutations and are enriched for unfavorable chromosomal losses of 9p21.3 when compared to non-infiltrated tumors. These data demonstrate how the interplay of somatic alterations and immunophenotypes impacts therapeutic efficacy.","abstract":"Immune checkpoint inhibitors targeting the PD-1 pathway have transformed the management of many advanced malignancies, including clear cell renal cell carcinoma (ccRCC), but the drivers and resistors of PD-1 response remain incompletely elucidated. Here, we analyzed 592 tumors collected from advanced ccRCC patients enrolled in prospective clinical trials of treatment with PD-1 blockade (or mTOR inhibition as control arm) by whole-exome and RNA-sequencing, integrated with immunofluorescence analysis, to define the somatic alteration landscape of late-stage ccRCC and to uncover the immunogenomic determinants of therapeutic response. While conventional genomic markers (tumor mutation burden, neoantigen load) and degree of CD8+ T cell infiltration were not associated with clinical response, we discovered numerous chromosomal alterations in advanced ccRCC associated with response or resistance to PD-1 blockade. These advanced tumors were highly CD8+ T cell infiltrated, with only 22% and 5% with an immune desert and immune excluded phenotype, respectively. Our analysis revealed that CD8+ infiltrated tumors are depleted of favorable PBRM1 mutations and are enriched for unfavorable chromosomal losses of 9p21.3 when compared to non-infiltrated tumors. These data demonstrate how the interplay of somatic alterations and immunophenotypes impacts therapeutic efficacy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-05T09:40:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004291","title":"Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell RCC -- CA209-010","description":"Immune checkpoint inhibitors targeting the PD-1 pathway have transformed the management of many advanced malignancies, including clear cell renal cell carcinoma (ccRCC), but the drivers and resistors of PD-1 response remain incompletely elucidated. Here, we analyzed 592 tumors collected from advanced ccRCC patients enrolled in prospective clinical trials of treatment with PD-1 blockade (or mTOR inhibition as control arm) by whole-exome and RNA-sequencing, integrated with immunofluorescence analysis, to define the somatic alteration landscape of late-stage ccRCC and to uncover the immunogenomic determinants of therapeutic response. While conventional genomic markers (tumor mutation burden, neoantigen load) and degree of CD8+ T cell infiltration were not associated with clinical response, we discovered numerous chromosomal alterations in advanced ccRCC associated with response or resistance to PD-1 blockade. These advanced tumors were highly CD8+ T cell infiltrated, with only 22% and 5% with an immune desert and immune excluded phenotype, respectively. Our analysis revealed that CD8+ infiltrated tumors are depleted of favorable PBRM1 mutations and are enriched for unfavorable chromosomal losses of 9p21.3 when compared to non-infiltrated tumors. These data demonstrate how the interplay of somatic alterations and immunophenotypes impacts therapeutic efficacy.","abstract":"Immune checkpoint inhibitors targeting the PD-1 pathway have transformed the management of many advanced malignancies, including clear cell renal cell carcinoma (ccRCC), but the drivers and resistors of PD-1 response remain incompletely elucidated. Here, we analyzed 592 tumors collected from advanced ccRCC patients enrolled in prospective clinical trials of treatment with PD-1 blockade (or mTOR inhibition as control arm) by whole-exome and RNA-sequencing, integrated with immunofluorescence analysis, to define the somatic alteration landscape of late-stage ccRCC and to uncover the immunogenomic determinants of therapeutic response. While conventional genomic markers (tumor mutation burden, neoantigen load) and degree of CD8+ T cell infiltration were not associated with clinical response, we discovered numerous chromosomal alterations in advanced ccRCC associated with response or resistance to PD-1 blockade. These advanced tumors were highly CD8+ T cell infiltrated, with only 22% and 5% with an immune desert and immune excluded phenotype, respectively. Our analysis revealed that CD8+ infiltrated tumors are depleted of favorable PBRM1 mutations and are enriched for unfavorable chromosomal losses of 9p21.3 when compared to non-infiltrated tumors. These data demonstrate how the interplay of somatic alterations and immunophenotypes impacts therapeutic efficacy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-05T09:41:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004292","title":"Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell RCC-- CA209-025","description":"Immune checkpoint inhibitors targeting the PD-1 pathway have transformed the management of many advanced malignancies, including clear cell renal cell carcinoma (ccRCC), but the drivers and resistors of PD-1 response remain incompletely elucidated. Here, we analyzed 592 tumors collected from advanced ccRCC patients enrolled in prospective clinical trials of treatment with PD-1 blockade (or mTOR inhibition as control arm) by whole-exome and RNA-sequencing, integrated with immunofluorescence analysis, to define the somatic alteration landscape of late-stage ccRCC and to uncover the immunogenomic determinants of therapeutic response. While conventional genomic markers (tumor mutation burden, neoantigen load) and degree of CD8+ T cell infiltration were not associated with clinical response, we discovered numerous chromosomal alterations in advanced ccRCC associated with response or resistance to PD-1 blockade. These advanced tumors were highly CD8+ T cell infiltrated, with only 22% and 5% with an immune desert and immune excluded phenotype, respectively. Our analysis revealed that CD8+ infiltrated tumors are depleted of favorable PBRM1 mutations and are enriched for unfavorable chromosomal losses of 9p21.3 when compared to non-infiltrated tumors. These data demonstrate how the interplay of somatic alterations and immunophenotypes impacts therapeutic efficacy.","abstract":"Immune checkpoint inhibitors targeting the PD-1 pathway have transformed the management of many advanced malignancies, including clear cell renal cell carcinoma (ccRCC), but the drivers and resistors of PD-1 response remain incompletely elucidated. Here, we analyzed 592 tumors collected from advanced ccRCC patients enrolled in prospective clinical trials of treatment with PD-1 blockade (or mTOR inhibition as control arm) by whole-exome and RNA-sequencing, integrated with immunofluorescence analysis, to define the somatic alteration landscape of late-stage ccRCC and to uncover the immunogenomic determinants of therapeutic response. While conventional genomic markers (tumor mutation burden, neoantigen load) and degree of CD8+ T cell infiltration were not associated with clinical response, we discovered numerous chromosomal alterations in advanced ccRCC associated with response or resistance to PD-1 blockade. These advanced tumors were highly CD8+ T cell infiltrated, with only 22% and 5% with an immune desert and immune excluded phenotype, respectively. Our analysis revealed that CD8+ infiltrated tumors are depleted of favorable PBRM1 mutations and are enriched for unfavorable chromosomal losses of 9p21.3 when compared to non-infiltrated tumors. These data demonstrate how the interplay of somatic alterations and immunophenotypes impacts therapeutic efficacy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-05T09:41:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004293","title":"MethCORR: DNA Methylation-based Characterization, Classification and Prognostication of Colorectal Cancer using Archival Formalin-fixed, Paraffin-embedded Tissue","description":"Transcriptional characterization and classification has potential to resolve the inter-tumor heterogeneity of colorectal cancer (CRC) and improve patient management. Yet, robust transcriptional profiling is difficult using formalin-fixed, paraffin-embedded (FFPE) samples, which complicates testing in clinical and archival material. We present MethCORR, an approach that allows uniform molecular characterization and classification of fresh-frozen and FFPE samples. MethCORR identifies genome-wide correlations between RNA expression and DNA methylation in fresh-frozen samples. This information is used to infer gene expression information in FFPE samples from their DNA methylation profiles. MethCORR was applied to methylation profiles from 877 fresh-frozen and FFPE samples and comparative analysis identified the same two major subtypes in four independent cohorts. Furthermore, subtype-specific prognostic biomarkers that better predicted relapse-free survival (HR=2.66, 95% CI [1.67-4.22], P&lt;0.001) than TNM staging and MSI status were identified and validated using DNA methylation-specific PCR assays. The MethCORR approach is general, and may be similarly successful for other cancer types.","abstract":"Transcriptional characterization and classification has potential to resolve the inter-tumor heterogeneity of colorectal cancer (CRC) and improve patient management. Yet, robust transcriptional profiling is difficult using formalin-fixed, paraffin-embedded (FFPE) samples, which complicates testing in clinical and archival material. We present MethCORR, an approach that allows uniform molecular characterization and classification of fresh-frozen and FFPE samples. MethCORR identifies genome-wide correlations between RNA expression and DNA methylation in fresh-frozen samples. This information is used to infer gene expression information in FFPE samples from their DNA methylation profiles. MethCORR was applied to methylation profiles from 877 fresh-frozen and FFPE samples and comparative analysis identified the same two major subtypes in four independent cohorts. Furthermore, subtype-specific prognostic biomarkers that better predicted relapse-free survival (HR=2.66, 95% CI [1.67-4.22], P&lt;0.001) than TNM staging and MSI status were identified and validated using DNA methylation-specific PCR assays. The MethCORR approach is general, and may be similarly successful for other cancer types.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-05T10:45:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004294","title":"Exome_Sequencing_of_The_Ageing_Brain__WES_","description":"Study the somatic mutation and the clonal architecture in neurons, including mutation burden accumulation through lifespan, mutational signatures and comparison between healthy and Alzheimer patients.","abstract":"Study the somatic mutation and the clonal architecture in neurons, including mutation burden accumulation through lifespan, mutational signatures and comparison between healthy and Alzheimer patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004295","title":"scRNAseq_of_tFoetal_muscle","description":"Cell atlas of foetal skeletal muscle system\n\nCell atlas of foetal skeletal muscle system - The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through; genetic and genomic analysis, expression analysis, non-identifiable video imaging and cell line and organoid production, as well as, computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequently validate these findings in situ using spatial genomic and imaging technologies e.g. immunohistochemistry, RNAscope, in situ sequencing and spatial transcriptomic analyses.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Cell atlas of foetal skeletal muscle system\n\nCell atlas of foetal skeletal muscle system - The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through; genetic and genomic analysis, expression analysis, non-identifiable video imaging and cell line and organoid production, as well as, computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequently validate these findings in situ using spatial genomic and imaging technologies e.g. immunohistochemistry, RNAscope, in situ sequencing and spatial transcriptomic analyses.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004296","title":"Molecular profiling of metastatic uveal melanoma","description":"Metastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations were overrepresented and occurred in 29/32 of cases. An outlier tumor had high mutational burden associated with UV-damage. CDKN2A deletions also occurred, which are rarely present in primaries. We profiled recurrent copy number alterations associated with metastasis and performed a focused knockdown screen on overexpressed targets. We investigated the role of BAP1 by reintroducing a functional allele into a deficient patient-derived cell line, revealing a broad shift towards a transcriptomic subtype associated with better prognosis. Tumor-infiltrating lymphocytes were in several cases tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 was abundant. This study represents the largest whole-genome analysis of uveal melanoma to date and presents an updated view of the metastatic disease.","abstract":"Metastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations were overrepresented and occurred in 29/32 of cases. An outlier tumor had high mutational burden associated with UV-damage. CDKN2A deletions also occurred, which are rarely present in primaries. We profiled recurrent copy number alterations associated with metastasis and performed a focused knockdown screen on overexpressed targets. We investigated the role of BAP1 by reintroducing a functional allele into a deficient patient-derived cell line, revealing a broad shift towards a transcriptomic subtype associated with better prognosis. Tumor-infiltrating lymphocytes were in several cases tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 was abundant. This study represents the largest whole-genome analysis of uveal melanoma to date and presents an updated view of the metastatic disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-05T17:43:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004297","title":"Histone H3 wild type DIPG overexpressing EZHIP extend the spectrum of DMG with PRC2 inhibition beyond H3K27M mutation","description":null,"abstract":"Characterization of new subgroup of DMG lacking H3-K27M mutation that is defined by H3K27me3 loss and EZHIP overexpression that can be detected by IHC. These tumors are distinct from EZHIP-positive posterior fossa ependymomas and are associated with a dismal prognosis. We propose that these H3-WT tumors need to be considered similar to canonical DIPG/DMG, thus extending the spectrum of PRC2-deficient DMG beyond H3-K27M mutation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004298","title":"IgCaller","description":"IgCaller is a python program designed to fully characterize the immunoglobulin (IG) gene rearrangements and oncogenic translocations in lymphoid neoplasms from whole-genome sequencing (WGS) data. Using a cohort of 331 patients comprising different subtypes of B-cell neoplasms, we demonstrate that IgCaller identifies both heavy and light chain rearrangements providing additional information on their functionality, somatic mutational status, class switch recombination, and oncogenic IG translocations. We provided here IG reads of the previously unpublished WGS.","abstract":"IgCaller is a python program designed to fully characterize the immunoglobulin (IG) gene rearrangements and oncogenic translocations in lymphoid neoplasms from whole-genome sequencing (WGS) data. Using a cohort of 331 patients comprising different subtypes of B-cell neoplasms, we demonstrate that IgCaller identifies both heavy and light chain rearrangements providing additional information on their functionality, somatic mutational status, class switch recombination, and oncogenic IG translocations. We provided here IG reads of the previously unpublished WGS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-09T08:16:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004299","title":"Imm_Fetal_Lung","description":"The aim of this study to assess a lung immune landscape within first and second trimester.  \n\nscRNA-seq for  CD45+ immune cell populations from lung tissue from fetuses spanning a range of ages within first and second trimester (8-20pcw)  for better understanding the lung immune landscape in pregnancy.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The aim of this study to assess a lung immune landscape within first and second trimester.  \n\nscRNA-seq for  CD45+ immune cell populations from lung tissue from fetuses spanning a range of ages within first and second trimester (8-20pcw)  for better understanding the lung immune landscape in pregnancy.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004300","title":"HuiPS_WT_C5aR1_KO_and_Kleb","description":"We want to analyse the effect of specific mutations in Inflammasome genes on macrophages derived from human iPS cells on infection with Klebsiella species\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We will analyse transcriptomics data from WT and gene KO Kolf2 human iPS derived macrophages after infection with various species of Klebsiella","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004301","title":"H3.3G34R/V-transformed interneuron progenitors co-opt PDGFRA for gliomagenesis","description":"Histone H3.3 glycine 34 to arginine/valine (H3.3G34R/V) mutations occur in deadly hemispheric high-grade gliomas. These tumors show exquisite regional and temporal specificity, suggesting a developmental context permissive to the effects of G34R/V mutations. Here we present the molecular landscape of G34R/V gliomas (n=85) and show that 50% bear activating mutations in PDGFRA, with strong selection pressure for PDGFRAMUT clones at recurrence. We show that G34R/V tumors arise in interneuron progenitors of the foetal ventral forebrain expressing GSX2 and the DLX family of homeobox transcription factors, where terminal neuronal differentiation is impaired through aberrant G34R/V-mediated H3K27me3. Frequent co-occurrence of G34R/V &amp; PDGFRAMUT is facilitated in this interneuron lineage-of-origin as PDGFRA forms an aberrant chromatin loop with the adjacent GSX2, hijacking its active chromatin conformation. At the single-cell level, G34R/V tumours entirely lack oligodendroglial transcriptional programs prominent in other glioma entities, and instead harbour dual neuronal and astroglial compartments. CRISPR-removal of H3.3G34R/V does not impact tumorigenicity suggesting this mutation becomes dispensable, while PDGFRAMUT are potently oncogenic regardless of G34 mutation. Collectively, our results suggest that G34R/V gliomas arise in foetal interneuron progenitors unable to undergo terminal differentiation, enabling co-option of PDGFRA through inappropriate expression and activating mutations to promote gliogenesis and oncogenicity. Reliance on PDGFRA for oncogenesis may be of therapeutic opportunity in G34R/V glioma.","abstract":"Histone H3.3 glycine 34 to arginine/valine (H3.3G34R/V) mutations occur in deadly hemispheric high-grade gliomas. These tumors show exquisite regional and temporal specificity, suggesting a developmental context permissive to the effects of G34R/V mutations. Here we present the molecular landscape of G34R/V gliomas (n=85) and show that 50% bear activating mutations in PDGFRA, with strong selection pressure for PDGFRAMUT clones at recurrence. We show that G34R/V tumors arise in interneuron progenitors of the foetal ventral forebrain expressing GSX2 and the DLX family of homeobox transcription factors, where terminal neuronal differentiation is impaired through aberrant G34R/V-mediated H3K27me3. Frequent co-occurrence of G34R/V &amp; PDGFRAMUT is facilitated in this interneuron lineage-of-origin as PDGFRA forms an aberrant chromatin loop with the adjacent GSX2, hijacking its active chromatin conformation. At the single-cell level, G34R/V tumours entirely lack oligodendroglial transcriptional programs prominent in other glioma entities, and instead harbour dual neuronal and astroglial compartments. CRISPR-removal of H3.3G34R/V does not impact tumorigenicity suggesting this mutation becomes dispensable, while PDGFRAMUT are potently oncogenic regardless of G34 mutation. Collectively, our results suggest that G34R/V gliomas arise in foetal interneuron progenitors unable to undergo terminal differentiation, enabling co-option of PDGFRA through inappropriate expression and activating mutations to promote gliogenesis and oncogenicity. Reliance on PDGFRA for oncogenesis may be of therapeutic opportunity in G34R/V glioma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-09T21:57:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004302","title":"Circulating cell-free DNA based methylation patterns for  diagnosis of early breast cancer","description":null,"abstract":"In plasma samples, the DNA methylation profiling were further filtered using a training set of 160 plasma samples and 26 markers were selected to build a diagnostic prediction model. From an independent validation set of additional 69 plasma samples, this model yielded a sensitivity of 89.36% (80.85% - 97.87%) and a specificity of 95.45% (86.36% - 100%) for differentiating malignant disease (n = 47) from normal lesions (n =22) (AUC 0.9816).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004303","title":"Egyptref: An integrated personal and population-based Egyptian genome reference","description":"North African individuals are not represented in current genetic data sets. To address this issue, we generated an integrated personal and population-based Egyptian genome reference called Egyptref. Towards this end, we performed a human de novo assembly of an Egyptian individual using long PacBio reads (99x genome coverage) and polished it using Illumina short reads (90x). Variants were phased using 10x Genomics linked reads (80x). This personal genome was complemented with whole genome sequencing-based variant data of 109 further Egyptians and mitochondrial haplogroups from mtDNA sequencing of 326 further Egyptians (of which 100 individuals from EGAD00001001372/EGAD00001001380) to obtain a population-based genome. We used Egyptref for assessing the impact of genetic variation, e.g. by integration of blood RNA sequencing data of the assembly individual.","abstract":"North African individuals are not represented in current genetic data sets. To address this issue, we generated an integrated personal and population-based Egyptian genome reference called Egyptref. Towards this end, we performed a human de novo assembly of an Egyptian individual using long PacBio reads (99x genome coverage) and polished it using Illumina short reads (90x). Variants were phased using 10x Genomics linked reads (80x). This personal genome was complemented with whole genome sequencing-based variant data of 109 further Egyptians and mitochondrial haplogroups from mtDNA sequencing of 326 further Egyptians (of which 100 individuals from EGAD00001001372/EGAD00001001380) to obtain a population-based genome. We used Egyptref for assessing the impact of genetic variation, e.g. by integration of blood RNA sequencing data of the assembly individual.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-10T06:12:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004304","title":"This is a test","description":null,"abstract":"This is a test","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004305","title":"scRNAseq_of_the_adult_immun_system","description":"Cell atlas of adult immune system\n\nCell atlas of Adult immune system - The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through; genetic and genomic analysis, expression analysis, non-identifiable video imaging and cell line and organoid production, as well as, computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequently validate these findings in situ using spatial genomic and imaging technologies e.g. immunohistochemistry, RNAscope, in situ sequencing and spatial transcriptomic analyses.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Cell atlas of adult immune system\n\nCell atlas of Adult immune system - The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through; genetic and genomic analysis, expression analysis, non-identifiable video imaging and cell line and organoid production, as well as, computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequently validate these findings in situ using spatial genomic and imaging technologies e.g. immunohistochemistry, RNAscope, in situ sequencing and spatial transcriptomic analyses.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004306","title":"Immunooncology_Cas9_IFNg_screen1","description":"Custom gRNA library previously used by Sarah Consonni. 4 cell pellet samples for DNA extraction and to be sequenced for gRNA.","abstract":"Need to use different primers for this as the plasmid is slightly different to Kosuke.\ngLibrary -HiSeq_50bp-SE_U1\tACACTCTTTCCCTACACGACGCTCTTCCGATCTGGCTTTATATATCTTGTGGAAAGGACGAGGTACC\ngLibrary -HiSeq_50bp-SE_L1\tTCGGCATTCCTGCTGAACCGCTCTTCCGATCTccgactcggtgccactttttcaag","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004307","title":"gel_spliceosome_rna","description":"We hypothesise that disease-causing genes involved in the spliceosome may have a global splicing signature that is detectable in blood with only a handful of individuals, as long as the gene is expressed in blood. This has been demonstrated previously in a couple of studies on individual spliceosome-related genes.  For example, defects in minor intron splicing were demonstrated through RNAseq in blood from two individuals with Roifman syndrome, a multi-system disorder caused by mutations in RNU4atac, versus just three controls (Merico et al, Nature Comms, 2015). Using exon microarray data, Hartong et al. (Lancet, 2006). showed pervasive splicing differences in blood from four individuals with mutations in the retinitis pigmentosa genes PRPF8 versus four sibling controls. We would like to explore the utility of RNAseq in blood for interpreting variants of unknown significance across multiple disease-causing spliceosome genes","abstract":"We have identified Genomics England rare disease patients with protein-coding variants in spliceosome genes, and had these variants reviewed by a clinical geneticist to class them as pathogenic, uncertain or benign. Then we obtained available RNA from the GEL patients (plus controls) and have done QC on these. Now we wish to RNA-sequence 95 individuals including ~75 cases with variants in one of 11 different spliceosome-related genes (up to 14 individuals per gene), plus ~19 controls who have variants in ion channel genes not expressed in blood. The project involves globin depletion of the RNA and then sequencing the 95 samples on a single NovaSeq lane with 100bp PE reads. We will test if there are pervasive differences in either minor or major intron splicing between cases with known pathogenic variants and controls/patients with known benign variants, and use this to try to interpret variants of unknown significance in these genes. We will also test whether particular biochemical pathways are enriched for splicing changes in patients with pathogenic mutations in specific genes, and evaluate whether these are likely to be particularly relevant to the phenotypic features associated with those mutations","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004308","title":"scRNAseq_of_the_adult_immun_system","description":"Cell atlas of adult immune system\n\nCell atlas of Adult immune system - The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through; genetic and genomic analysis, expression analysis, non-identifiable video imaging and cell line and organoid production, as well as, computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequently validate these findings in situ using spatial genomic and imaging technologies e.g. immunohistochemistry, RNAscope, in situ sequencing and spatial transcriptomic analyses.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Cell atlas of adult immune system\n\nCell atlas of Adult immune system - The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through; genetic and genomic analysis, expression analysis, non-identifiable video imaging and cell line and organoid production, as well as, computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequently validate these findings in situ using spatial genomic and imaging technologies e.g. immunohistochemistry, RNAscope, in situ sequencing and spatial transcriptomic analyses.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004309","title":"Thymic_organoid","description":"Single cell RNA sequencing of cells from thymic organoids, which include differentiating human iPSCs and mouse stromal cells.\n\nThere are many different T cell subsets which carry out different immune functions. Examples include cytotoxic CD8+ T cells that protect us against infection and cancer, and suppressive T regulatory cells (Tregs) that keep immune reactions under control. The power of T cells has been harnessed and widely applied in various fields of clinical medicine. Current examples include chimeric antigen receptor (CAR) T cells in cancer immunotherapy [1, 2]. At the same time, Tregs with their special suppressive function, have been used in autoimmune diseases and solid organ transplantation [3, 4] to try to establish tolerance. \n\nThe thymus is a unique organ where T cells mature and develop into different lineages. Our lab has recently elucidated a comprehensive transcriptional network of T cell development by performing single-cell RNA-seq in human thymus across different developmental stages i.e. embryo, fetus, child, and adult (manuscript under revision at Science). We now have a good understanding of which transcription factors are involved in development of different T cell lineages in vivo.\n\nA recent paper from Montel-Hagen et al. [5] has built the most efficient in vitro system to date in order to generate mature T cells from stem cells including induced pluripotent stem cells (iPSCs) utilising an artificial thymic organoid system (ATO). The main output from this current ATO system is CD8 single positive T cells, with very few CD4 T cells and even fewer Tregs. We aim to induce expression of the key transcription factors identified from our human thymus sequencing study, to engineer T cell development towards Tregs in this in vitro system. Our end goal is to generate ‘off-the-shelf’ suppressive Tregs. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Single cell RNA sequencing of cells from thymic organoids, which include differentiating human iPSCs and mouse stromal cells.\n\nThere are many different T cell subsets which carry out different immune functions. Examples include cytotoxic CD8+ T cells that protect us against infection and cancer, and suppressive T regulatory cells (Tregs) that keep immune reactions under control. The power of T cells has been harnessed and widely applied in various fields of clinical medicine. Current examples include chimeric antigen receptor (CAR) T cells in cancer immunotherapy [1, 2]. At the same time, Tregs with their special suppressive function, have been used in autoimmune diseases and solid organ transplantation [3, 4] to try to establish tolerance. \n\nThe thymus is a unique organ where T cells mature and develop into different lineages. Our lab has recently elucidated a comprehensive transcriptional network of T cell development by performing single-cell RNA-seq in human thymus across different developmental stages i.e. embryo, fetus, child, and adult (manuscript under revision at Science). We now have a good understanding of which transcription factors are involved in development of different T cell lineages in vivo.\n\nA recent paper from Montel-Hagen et al. [5] has built the most efficient in vitro system to date in order to generate mature T cells from stem cells including induced pluripotent stem cells (iPSCs) utilising an artificial thymic organoid system (ATO). The main output from this current ATO system is CD8 single positive T cells, with very few CD4 T cells and even fewer Tregs. We aim to induce expression of the key transcription factors identified from our human thymus sequencing study, to engineer T cell development towards Tregs in this in vitro system. Our end goal is to generate ‘off-the-shelf’ suppressive Tregs. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004310","title":"HCA_Thymus_Disease","description":"Single cell RNA sequencing on thymic cells from children with syndromic diseases such as Trisomy 21 and inflammatory/autoimmune diseases such as myasthenia gravis. \n\nOur group has previously performed atlasing of the healthy human thymus using single cell transcriptomics and obtained an unprecedented understanding of human thymus throughout development. \nIn this study, we intend to survey diseased human thymus and compare this to healthy to obtain a better understanding of thymic dysfunction in human diseases. The diseases we will survey include congenital conditions such as Down's syndrome, CHARGE syndrome, DiGeorge syndrome as well as acquired diseases such as myasthenia gravis and thymic hyperplasia. We intend to perform genetic and genomic study on the samples, including expression analysis. This will not only help us to understand the cells and molecular pathways affected in dysfunctional thymus; but may also lead to generalisable understandings in human genetic diseases and inflammatory/autoimmune diseases.      \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Single cell RNA sequencing on thymic cells from children with syndromic diseases such as Trisomy 21 and inflammatory/autoimmune diseases such as myasthenia gravis. \n\nOur group has previously performed atlasing of the healthy human thymus using single cell transcriptomics and obtained an unprecedented understanding of human thymus throughout development. \nIn this study, we intend to survey diseased human thymus and compare this to healthy to obtain a better understanding of thymic dysfunction in human diseases. The diseases we will survey include congenital conditions such as Down's syndrome, CHARGE syndrome, DiGeorge syndrome as well as acquired diseases such as myasthenia gravis and thymic hyperplasia. We intend to perform genetic and genomic study on the samples, including expression analysis. This will not only help us to understand the cells and molecular pathways affected in dysfunctional thymus; but may also lead to generalisable understandings in human genetic diseases and inflammatory/autoimmune diseases.      \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-12T10:33:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004311","title":"Healthy_ageing_thymus","description":"Single cell RNA sequencing of immune and non-immune cells from healthy ageing thymus\n\nThymus is a primary lymphoid organ that creates an environment for the T lymphocyte precursors differentiation into the naive T cells, which involves TCR gene rearrangement, negative and positive selection. Despite thymus critical function for the recognition of the pathogens it starts to atrophy very early in life. Thymic Epithelial Space (TES), where thymocyte education occurs, starts to decline rapidly just after birth, while with the onset of puberty thymus  is also progressively replaced with adipose tissue. This leads to a reduced naive T cell output,which decreases an organism's ability to recognize pathogens.\nIn our lab, we have already collected and characterized cell type composition and gene regulatory networks of the fetal tand adult human thymus (Park et al, Science 2020). In the current project we plan to expand the number of paediatric and adult samples in the study with the aim to understand how the process of thymic involution happens. We will use single-cell transcriptomics to zoom on changes that occur in immune and non-immune cell types in different phases of thymic involution with the hope to understand which gene expression changes are causal for the thymic involution process and how naïve T cell production can be increased in elderly.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Single cell RNA sequencing of immune and non-immune cells from healthy ageing thymus\n\nThymus is a primary lymphoid organ that creates an environment for the T lymphocyte precursors differentiation into the naive T cells, which involves TCR gene rearrangement, negative and positive selection. Despite thymus critical function for the recognition of the pathogens it starts to atrophy very early in life. Thymic Epithelial Space (TES), where thymocyte education occurs, starts to decline rapidly just after birth, while with the onset of puberty thymus  is also progressively replaced with adipose tissue. This leads to a reduced naive T cell output,which decreases an organism's ability to recognize pathogens.\nIn our lab, we have already collected and characterized cell type composition and gene regulatory networks of the fetal tand adult human thymus (Park et al, Science 2020). In the current project we plan to expand the number of paediatric and adult samples in the study with the aim to understand how the process of thymic involution happens. We will use single-cell transcriptomics to zoom on changes that occur in immune and non-immune cell types in different phases of thymic involution with the hope to understand which gene expression changes are causal for the thymic involution process and how naïve T cell production can be increased in elderly.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-12T12:43:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004312","title":"PFA ependymoma cancer study","description":"Sequencing data related the PFA ependymoma study (Michealraj et al., Cell 2020), a lethal glial malignancy of the hindbrain found in babies and toddlers.","abstract":"Sequencing data related the PFA ependymoma study (Michealraj et al., Cell 2020), a lethal glial malignancy of the hindbrain found in babies and toddlers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-14T14:07:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004313","title":"Gradient of developmental and injury-response transcriptional states defines roots of glioblastoma heterogeneity","description":"XXX","abstract":"XXX","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004314","title":"Circulating tumor cells for comprehensive and multiregional non-invasive genetic characterization of multiple myeloma (arrays set)","description":"Multiple myeloma (MM) patients undergo repetitive bone marrow (BM) aspirates for genetic characterization. Circulating tumor cells (CTCs) are detectable in peripheral blood of virtually all MM cases and are prognostic, but their applicability for non-invasive screening has been poorly investigated. Here, we used next-generation flow cytometry to isolate matched CTCs and BM tumor cells from 42 patients and compare their genetic profile. In 8 cases, tumor cells from extramedullary plasmacytomas were also sorted and whole-exome sequencing performed in the three spatially-distributed clones. Noteworthy, ≥84% mutations present in BM and extramedullary clones were detectable in CTCs. Concordance between BM tumor cells and CTCs was high for chromosome arm-level copy-number alterations (≥94%) though not for translocations (43%). All high-risk genetic abnormalities except one t(4;14) were detected in CTCs whenever present in BM tumor cells. Altogether, these results support CTCs for non-invasive risk-stratification of MM patients based on their numbers and genetic profile.","abstract":"Multiple myeloma (MM) patients undergo repetitive bone marrow (BM) aspirates for genetic characterization. Circulating tumor cells (CTCs) are detectable in peripheral blood of virtually all MM cases and are prognostic, but their applicability for non-invasive screening has been poorly investigated. Here, we used next-generation flow cytometry to isolate matched CTCs and BM tumor cells from 42 patients and compare their genetic profile. In 8 cases, tumor cells from extramedullary plasmacytomas were also sorted and whole-exome sequencing performed in the three spatially-distributed clones. Noteworthy, ≥84% mutations present in BM and extramedullary clones were detectable in CTCs. Concordance between BM tumor cells and CTCs was high for chromosome arm-level copy-number alterations (≥94%) though not for translocations (43%). All high-risk genetic abnormalities except one t(4;14) were detected in CTCs whenever present in BM tumor cells. Altogether, these results support CTCs for non-invasive risk-stratification of MM patients based on their numbers and genetic profile.","study_type":"Other","pubmed_ids":[32475991],"external_links":null,"is_released":true,"released_date":"2020-03-19T10:48:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004315","title":"Enhancer-gene rewiring in the pathogenesis of Quebec Platelet Disorder","description":null,"abstract":"Quebec Platelet Disorder (QPD) is an autosomal dominant  bleeding disorder caused by a 78kb tandem duplication of PLAU and is characterized by &gt;100-fold increased levels of urokinase plasminogen activator (PLAU) transcripts and protein in megakaryocytes/platelets but not leukocytes, without increased systemic fibrinolysis. To address the cell-type and allele-specific PLAU overexpression that underlie QPD pathogenesis,we used epigenomic profiling, comparative genomics and chromatin conformation capture approaches to study PLAU regulation in cultured megakaryocytes. We show that the QPD duplication leads to ectopic interactions between PLAU and a conserved megakaryocyte enhancer found within the same topologically associating domain (TAD). Our results support a unique disease mechanism whereby the reorganization of sub-TAD genome architecture results in a dramatic, cell-type specific disease phenotype.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-19T19:33:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004316","title":"Hereditary Cancer Diagnostics with I2HCP gene panel","description":"This dataset contains targetted DNA sequencing data generated in the context of genetic diagnostics of hereditary cancer. Target enrichment was performed with the I2HCP, a custom hereditary cancer gene panel based in Agilent SureSelect and developed by the Germans Trias i Pujol Research Institute (IGTP, Badalona, Catalonia, Spain) and the Catalan Institute of Oncology (ICO, L'Hospitalet de Llobregat, Catalonia, Spain). After the enrichment, 108 samples were sequenced in Illumina HiSeq machines and 130 in MiSeq machines. Some of the samples were sequenced on both platforms. The dataset also includes MLPA validation data for all identified copy-number alterations, annotated with exon resolution and information about negative MLPA results. \nAll this data was generated in the context of routine diagnostics and compiled together with MPLA validation data for a genetic diagnostics oriented benchmark of germline CNV calling tools.","abstract":"This dataset contains targetted DNA sequencing data generated in the context of genetic diagnostics of hereditary cancer. Target enrichment was performed with the I2HCP, a custom hereditary cancer gene panel based in Agilent SureSelect and developed by the Germans Trias i Pujol Research Institute (IGTP, Badalona, Catalonia, Spain) and the Catalan Institute of Oncology (ICO, L'Hospitalet de Llobregat, Catalonia, Spain). After the enrichment, 108 samples were sequenced in Illumina HiSeq machines and 130 in MiSeq machines. Some of the samples were sequenced on both platforms. The dataset also includes MLPA validation data for all identified copy-number alterations, annotated with exon resolution and information about negative MLPA results. \nAll this data was generated in the context of routine diagnostics and compiled together with MPLA validation data for a genetic diagnostics oriented benchmark of germline CNV calling tools.","study_type":"Other","pubmed_ids":[28050010,28051113],"external_links":null,"is_released":true,"released_date":"2020-03-20T01:58:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004317","title":"Whole-Exome Sequencing Reveals Critical Genes Underlying Metastasis in Esophageal Squamous Cell Carcinoma","description":null,"abstract":"Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers due to a high frequency of metastasis. However, little is known about the genomic landscape of metastatic ESCC. To identify the genetic alterations that underlie ESCC metastasis, whole-exome sequencing (WES) was performed for 41 primary tumors and 15 lymph nodes (LNs) with metastatic ESCC. Eleven cases included matched primary tumors, synchronous LN metastases and non-neoplastic mucosa.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004318","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__Pancreas_Novaseq","description":"he Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"he Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004319","title":"Long-read trio sequencing of unsolved patients with intellectual disability","description":"Long-read sequencing (LRS) has the potential to comprehensively identify all medically-relevant genome variation, including variation commonly missed by short read sequencing (SRS) approaches. To determine this potential, we performed LRS up to 40x coverage using the Pacific Biosciences Sequel instrument for 5 patient-parent trios with intellectual disability, whose aetiology remained unresolved after SRS exomes and genomes. \nA first systematic assessment of LRS coverage showed that ~35Mb of the genome was only accessible by LRS and not SRS. Structural variant (SV) calling yielded on average 28,292 SV calls per individual, totalling 12.9 MB of sequence. Trio-based analyses showed concordance for up to 95% of these SV calls across the genome, and 80% of the LRS SV calls were not identified by SRS. De novo mutation analysis did not identify any de novo SVs, confirming these are rare events. Because of high sequence coverage, we were also able to call single nucleotide substitutions. On average, we identified 3 million substitutions per genome, with a Mendelian inheritance concordance of up to 97%. Of these, approximately 100,000 were located in the ~35Mb of the genome that was only captured by LRS. Moreover, these variants affected the coding sequence of 64 genes, including 32 known to cause Mendelian disorders. \nAlthough no clinical diagnoses were made in these 5 patients, our data show the potential added value of LRS compared to SRS for identifying medically relevant genome variation.","abstract":"Long-read sequencing (LRS) has the potential to comprehensively identify all medically-relevant genome variation, including variation commonly missed by short read sequencing (SRS) approaches. To determine this potential, we performed LRS up to 40x coverage using the Pacific Biosciences Sequel instrument for 5 patient-parent trios with intellectual disability, whose aetiology remained unresolved after SRS exomes and genomes. \nA first systematic assessment of LRS coverage showed that ~35Mb of the genome was only accessible by LRS and not SRS. Structural variant (SV) calling yielded on average 28,292 SV calls per individual, totalling 12.9 MB of sequence. Trio-based analyses showed concordance for up to 95% of these SV calls across the genome, and 80% of the LRS SV calls were not identified by SRS. De novo mutation analysis did not identify any de novo SVs, confirming these are rare events. Because of high sequence coverage, we were also able to call single nucleotide substitutions. On average, we identified 3 million substitutions per genome, with a Mendelian inheritance concordance of up to 97%. Of these, approximately 100,000 were located in the ~35Mb of the genome that was only captured by LRS. Moreover, these variants affected the coding sequence of 64 genes, including 32 known to cause Mendelian disorders. \nAlthough no clinical diagnoses were made in these 5 patients, our data show the potential added value of LRS compared to SRS for identifying medically relevant genome variation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-24T16:28:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004320","title":"Multiregion Whole-Exome Sequencing Uncovers the Genetic Evolution and Mutational Heterogeneity of Early-Stage Metastatic Melanoma.","description":null,"abstract":"Cancer genome sequencing has shed light on the underlying genetic aberrations that drive tumorigenesis. However, current sequencing-based strategies, which focus on a single tumor biopsy, fail to take into account intratumoral heterogeneity. To address this challenge and elucidate the evolutionary history of melanoma, we performed whole-exome and transcriptome sequencing of 41 multiple melanoma biopsies from eight individual tumors. This approach revealed heterogeneous somatic mutations in the range of 3%-38% in individual tumors. Known mutations in melanoma drivers BRAF and NRAS were always ubiquitous events. Using RNA sequencing, we found that the majority of mutations were not expressed or were expressed at very low levels, and preferential expression of a particular mutated allele did not occur frequently. In addition, we found that the proportion of ultraviolet B (UVB) radiation-induced C&gt;T transitions differed significantly (P &lt; 0.001) between early and late mutation acquisition, suggesting that different mutational processes operate during the evolution of metastatic melanoma. Finally, clinical history reports revealed that patients harboring a high degree of mutational heterogeneity were associated with more aggressive disease progression. In conclusion, our multiregion tumor-sequencing approach highlights the genetic evolution and non-UVB mutational signatures associated with melanoma development and progression, and may provide a more comprehensive perspective of patient outcome. Cancer Res; 76(16); 4765-74.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-24T17:12:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004321","title":"Direct_mutational_consequences_of_CRISPR_cas9_knockouts_of_DNA_repair_genes","description":"Analysis of mutational signatures caused by DNA repair defects in human induced pluripotent stem (iPS) cells. A reference human iPS cell line will be used for genetic manipulation to introduce homozygous knockouts of 100 genes known to be involved in or connected to DNA repair or DNA editing. Following a defined period of growth after homozygous knockout of each gene, sub clones will be generated and sequenced. The progenitor “parental” IPS cell line will be used to generate reference sequence data, in order to determine the mutational signature acquired due to the gene knockout.","abstract":"Biallelic knockouts of DNA repair genes in a human induced pluripotent stem cell (hIPSC) model system reveal substitution and indel mutational signatures. Notably, dissection of signatures of defective mismatch repair (MMR) uncovers gene-specific characteristics including distinguishing features of MLH1, MSH2, and MSH6 from PMS2. This gene-specificity is also exhibited by hIPSCs derived from patients with autosomal recessive Constitutional Mismatch Repair Deficiency (CMMRD) that carry germline mutations of MMR genes. Furthermore, gene-specificity manifests in whole genome sequenced primary human cancers. Detailed analyses reveal putative sources of endogenous DNA damage that contribute to MMR signatures, including guanine oxidation, errors of polymerase  epsilon, alpha and delta, and reversed template slippage or double slippage. Finally, we find that using all mutational signatures of MMR-deficiency as identified in this study, results in improved sensitivity and specificity in classifying MMR-deficient tumors, critical for accurate patient stratification for therapeutic intervention.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004322","title":"Rare_renal_tumours_WGS_","description":"Rare renal tumours are by hard to classify and there is very little available information regarding prognosis and sensitivity to treatment. Here we endevour to understand their genomic properties in order to better understand their biology.","abstract":"Rare renal tumours are by hard to classify and there is very little available information regarding prognosis and sensitivity to treatment. Here we endevour to understand their genomic properties in order to better understand their biology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-25T14:02:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004323","title":"Rare_renal_tumours_RNA_","description":"Rare renal tumours are by hard to classify and there is very little available information regarding prognosis and sensitivity to treatment. Here we endevour to understand their genomic properties in order to better understand their biology.","abstract":"Rare renal tumours are by hard to classify and there is very little available information regarding prognosis and sensitivity to treatment. Here we endevour to understand their genomic properties in order to better understand their biology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-25T14:17:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004324","title":"Whole genome sequencing - Bipolar disorder","description":"Identification of causative genetic variants leading to the development of bipolar disorder (BD) could result in genetic tests that would facilitate diagnosis. A better understanding of affected genes and pathways is also necessary for targeting of genes that may improve treatment strategies Here, we performed  whole genome sequencing (WGS) in six patients and three healthy controls.","abstract":"Identification of causative genetic variants leading to the development of bipolar disorder (BD) could result in genetic tests that would facilitate diagnosis. A better understanding of affected genes and pathways is also necessary for targeting of genes that may improve treatment strategies Here, we performed  whole genome sequencing (WGS) in six patients and three healthy controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004325","title":"Atypical 3q26/MECOM rearrangements genocopy inv(3)/t(3;3) in acute myeloid leukemia","description":"Acute myeloid leukemia (AML) with inv(3)/t(3;3)(q21q26) is a distinct WHO recognized entity, characterized by its aggressive course and poor prognosis. In this subtype of AML, the translocation of a GATA2 enhancer (3q21) to MECOM (3q26) results in overexpression of the MECOM isoform EVI1 and monoallelic expression of GATA2 from the unaffected allele. The full-length MECOM transcript, MDS1-EVI1, is not expressed as the result of the 3q26 rearrangement. Besides the classical inv(3)/t(3;3), a number of other 3q26/MECOM rearrangements with poor treatment response have been reported in AML. Here we demonstrate, in a group of 33 AML patients with atypical 3q26 rearrangements, MECOM involvement with EVI1 overexpression, but no or low MDS1-EVI1 levels. Moreover, the 3q26 translocations in these AML patients often involve super-enhancers of genes active in myeloid development (e.g. CD164, PROM1, CDK6 or MYC). In more than 50% of these cases allele specific GATA2 expression was observed, either by copy number loss or by an unexplained allelic imbalance. Altogether, atypical 3q26 recapitulate the main leukemic mechanism of inv(3)/t(3;3) AML, namely EVI1 overexpression driven by enhancer hijacking, absent MDS1-EVI1 expression and potential GATA2 involvement. Therefore, we conclude that both atypical 3q26/MECOM and inv(3)/t(3;3) can be classified as a single entity of 3q26-rearranged AMLs. Routine analyses determining MECOM rearrangements, EVI1 and MDS1-EVI1 expression are required to recognize 3q-rearranged AML cases.","abstract":"Acute myeloid leukemia (AML) with inv(3)/t(3;3)(q21q26) is a distinct WHO recognized entity, characterized by its aggressive course and poor prognosis. In this subtype of AML, the translocation of a GATA2 enhancer (3q21) to MECOM (3q26) results in overexpression of the MECOM isoform EVI1 and monoallelic expression of GATA2 from the unaffected allele. The full-length MECOM transcript, MDS1-EVI1, is not expressed as the result of the 3q26 rearrangement. Besides the classical inv(3)/t(3;3), a number of other 3q26/MECOM rearrangements with poor treatment response have been reported in AML. Here we demonstrate, in a group of 33 AML patients with atypical 3q26 rearrangements, MECOM involvement with EVI1 overexpression, but no or low MDS1-EVI1 levels. Moreover, the 3q26 translocations in these AML patients often involve super-enhancers of genes active in myeloid development (e.g. CD164, PROM1, CDK6 or MYC). In more than 50% of these cases allele specific GATA2 expression was observed, either by copy number loss or by an unexplained allelic imbalance. Altogether, atypical 3q26 recapitulate the main leukemic mechanism of inv(3)/t(3;3) AML, namely EVI1 overexpression driven by enhancer hijacking, absent MDS1-EVI1 expression and potential GATA2 involvement. Therefore, we conclude that both atypical 3q26/MECOM and inv(3)/t(3;3) can be classified as a single entity of 3q26-rearranged AMLs. Routine analyses determining MECOM rearrangements, EVI1 and MDS1-EVI1 expression are required to recognize 3q-rearranged AML cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-26T09:34:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004326","title":"Overrepresentation of genetic variation in the AnkyrinG interactome is related to a range of neurological disorders","description":"Upon the discovery of numerous genes involved in the pathogenesis of neurodevelopmental disorders, several studies showed that a significant proportion of these genes converge on common pathways and protein networks. Here, we  used a reversed approach, by screening the well-characterized AnkyrinG protein-protein interaction network, implicated in a variety of neurodevelopmental disorders, for genetic variation in a large cohort of 1009 cases with neurodevelopmental disorder. We identified a significant enrichment of de novo potentially disease-causing variants in this network, confirming that this protein network plays an important role in the emergence of several neurodevelopmental disorders.","abstract":"Upon the discovery of numerous genes involved in the pathogenesis of neurodevelopmental disorders, several studies showed that a significant proportion of these genes converge on common pathways and protein networks. Here, we  used a reversed approach, by screening the well-characterized AnkyrinG protein-protein interaction network, implicated in a variety of neurodevelopmental disorders, for genetic variation in a large cohort of 1009 cases with neurodevelopmental disorder. We identified a significant enrichment of de novo potentially disease-causing variants in this network, confirming that this protein network plays an important role in the emergence of several neurodevelopmental disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-26T10:07:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004327","title":"METABRIC: Data from Batra et al (2021); DNA methylation landscapes of 1538 breast cancers reveal a replication-linked clock, epigenomic instability and cis-regulation","description":"DNA methylation is aberrant in cancer, but the dynamics, regulatory role and clinical implications of such epigenetic changes are still poorly understood. Here, RRBS-based profiles of 1538 breast tumors and 244 normal breast tissues from the METABRIC cohort are reported, facilitating detailed analysis of DNA methylation within a rich context of genomic, transcriptional, and clinical data. Tumor methylation from immune and stromal signatures are deconvoluted leading to the discovery of a tumor replication-linked clock with genome-wide methylation loss in non-CpG island sites. Unexpectedly, methylation in most tumor CpG islands follows two replication-independent processes of gain (MG) or loss (ML) that we term epigenomic instability. Epigenomic instability is correlated with tumor grade and stage, TP53 mutations and poorer prognosis.  After controlling for these global trans-acting trends, as well as for X-linked dosage compensation effects, cis-specific methylation and expression correlations are uncovered at hundreds of promoters and over a thousand distal elements. Some of these targeted known tumor suppressors and oncogenes. In conclusion, the study demonstrates that global epigenetic instability can erode cancer methylomes and expose them to localized methylation aberrations in-cis resulting in transcriptional changes seen in tumors.","abstract":"DNA methylation is aberrant in cancer, but the dynamics, regulatory role and clinical implications of such epigenetic changes are still poorly understood. Here, RRBS-based profiles of 1538 breast tumors and 244 normal breast tissues from the METABRIC cohort are reported, facilitating detailed analysis of DNA methylation within a rich context of genomic, transcriptional, and clinical data. Tumor methylation from immune and stromal signatures are deconvoluted leading to the discovery of a tumor replication-linked clock with genome-wide methylation loss in non-CpG island sites. Unexpectedly, methylation in most tumor CpG islands follows two replication-independent processes of gain (MG) or loss (ML) that we term epigenomic instability. Epigenomic instability is correlated with tumor grade and stage, TP53 mutations and poorer prognosis.  After controlling for these global trans-acting trends, as well as for X-linked dosage compensation effects, cis-specific methylation and expression correlations are uncovered at hundreds of promoters and over a thousand distal elements. Some of these targeted known tumor suppressors and oncogenes. In conclusion, the study demonstrates that global epigenetic instability can erode cancer methylomes and expose them to localized methylation aberrations in-cis resulting in transcriptional changes seen in tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-27T15:18:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004328","title":"Activating AKT1 and PIK3CA mutations in metastatic castration-resistant prostate cancer","description":null,"abstract":"Activating mutations in AKT1 and PIK3CA are under-characterised in metastatic castration-resistant prostate cancer (mCRPC), but in other cancers are linked to PI3K signaling activation and sensitivity to pathway inhibitors. Our objective was to determine the prevalence, genomic context, and clinical associations of AKT1/PIK3CA activating mutations in mCRPC.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-27T18:22:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004329","title":"Genomic_landscape_of_liver_cirrhosis","description":"We are interested in the genomic landscape of liver cirrhosis and its potential manifestations for liver physiology and risk for hepatocellular carcinoma. Previous work in CASM has shown that there is a strong element of clonality within cirrhotic nodules and that some recurring mutations have been identified. However how this relates to the overall liver is not known and therefore by taking geographically disparate biospies, we aim to correlate our findings and make conclusions as to the characteristics of the overall genomic landscape.","abstract":"We are interested in the genomic landscape of liver cirrhosis and its potential manifestations for liver physiology and risk for hepatocellular carcinoma. Previous work in CASM has shown that there is a strong element of clonality within cirrhotic nodules and that some recurring mutations have been identified. However how this relates to the overall liver is not known and therefore by taking geographically disparate biospies, we aim to correlate our findings and make conclusions as to the characteristics of the overall genomic landscape.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-03-29T11:45:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004330","title":"MutWP6__CRUK_Grand_Challenge_Mutographs_of_Cancer__Botseq","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nWithin Mutographs, work lead by the Sanger Institute will investigate whether detection of somatic mutations and mutational signatures in circulating white blood cells can be developed into a practical, generic system for surveying and monitoring multiple different endogenous and exogenous exposures, providing an ‘observatory’ on somatic mutational processes in humans.\n\nWhole genome sequences are generated at the Wellcome Sanger Institute (Illumina HiSeqX). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nWithin Mutographs, work lead by the Sanger Institute will investigate whether detection of somatic mutations and mutational signatures in circulating white blood cells can be developed into a practical, generic system for surveying and monitoring multiple different endogenous and exogenous exposures, providing an ‘observatory’ on somatic mutational processes in humans.\n\nWhole genome sequences are generated at the Wellcome Sanger Institute (Illumina HiSeqX). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-02T11:16:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004331","title":"Somatic_mutations_in_HSCs_of_patients_with_chromosome_instability_syndromes_WGS__","description":"Chromosome instability syndromes, such as Fanconi anaemia or Bloom syndrome, are clinically distinct syndromes characterized by unique pattern of chromosomal damage. These syndromes are associated with a predisposition to cancer, including haematological malignancies. In this study, single cell-derived haematopoietic stem cell (HSC) colonies obtained from each individual will been grown to study the genetic background of haematological phenotypes and cancer predisposition of these syndromes at the single-cell level. Using whole-genome sequencing, we will analyse the genetic landscape, such as mutational burden, mutational signature and driver mutations, in HSCs. We also study clonal dynamics of HSCs and their telomere length using sequencing data.","abstract":"Chromosome instability syndromes, such as Fanconi anaemia or Bloom syndrome, are clinically distinct syndromes characterized by unique pattern of chromosomal damage. These syndromes are associated with a predisposition to cancer, including haematological malignancies. In this study, single cell-derived haematopoietic stem cell (HSC) colonies obtained from each individual will been grown to study the genetic background of haematological phenotypes and cancer predisposition of these syndromes at the single-cell level. Using whole-genome sequencing, we will analyse the genetic landscape, such as mutational burden, mutational signature and driver mutations, in HSCs. We also study clonal dynamics of HSCs and their telomere length using sequencing data.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004332","title":"Whole-genome and transcriptome sequencing of primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma","description":"Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (pcAECyTCL) is a rare variant of cutaneous T-cell lymphoma with an aggressive clinical course and a very poor prognosis. We subjected tumor biopsies from patients with pcAECyTCL to whole-genome sequencing and RNA-sequencing to investigate genomic alterations and deregulated gene expression in the disease.","abstract":"Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (pcAECyTCL) is a rare variant of cutaneous T-cell lymphoma with an aggressive clinical course and a very poor prognosis. We subjected tumor biopsies from patients with pcAECyTCL to whole-genome sequencing and RNA-sequencing to investigate genomic alterations and deregulated gene expression in the disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-03T09:47:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004333","title":"Giselle","description":"does this work","abstract":"does this work","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004334","title":"Whole Genome Medical Sequencing for Genome Discovery","description":null,"abstract":"This study follows the incidence of Mental Retardation, Congenital Anomaly and Rare Disorders in families let´s say.\nHere DNA of subjects is sequenced and disease diagnoses and sign reports by clinicians are registered as yes/no let´s say.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004335","title":"Dissecting intratumor heterogeneity of nodal B cell lymphoma on the transcriptional, genetic, and drug response level","description":"Tumor heterogeneity encompasses both the malignant cells and their microenvironment. While heterogeneity between individual patients is well-known to affect the efficacy of anti-cancer, most personalized treatment approaches do not account for intratumor heterogeneity. We addressed this issue by studying the heterogeneity of lymph node-derived B cell non-Hodgkin lymphoma (B-NHL) by single cell RNA-sequencing (scRNA-seq) and transcriptome-informed flow cytometry. We identified transcriptionally distinct malignant subclones and compared their drug response and genomic profiles. Malignant subclones of the same patient responded strikingly different to anti-cancer drugs ex vivo, which recapitulated subclone-specific drug sensitivity during in vivo treatment. Tumor infiltrating T cells represented the majority of non-malignant cells, whose gene expression signatures were similar across all donors, whereas the frequencies of T cell subsets varied significantly between the donors. Our data provide new insights into the heterogeneity of B-NHL and highlight the relevance of intratumor heterogeneity for personalized cancer therapies.","abstract":"Tumor heterogeneity encompasses both the malignant cells and their microenvironment. While heterogeneity between individual patients is well-known to affect the efficacy of anti-cancer, most personalized treatment approaches do not account for intratumor heterogeneity. We addressed this issue by studying the heterogeneity of lymph node-derived B cell non-Hodgkin lymphoma (B-NHL) by single cell RNA-sequencing (scRNA-seq) and transcriptome-informed flow cytometry. We identified transcriptionally distinct malignant subclones and compared their drug response and genomic profiles. Malignant subclones of the same patient responded strikingly different to anti-cancer drugs ex vivo, which recapitulated subclone-specific drug sensitivity during in vivo treatment. Tumor infiltrating T cells represented the majority of non-malignant cells, whose gene expression signatures were similar across all donors, whereas the frequencies of T cell subsets varied significantly between the donors. Our data provide new insights into the heterogeneity of B-NHL and highlight the relevance of intratumor heterogeneity for personalized cancer therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-06T08:30:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004336","title":"Genomic_profiling_of_Adult_ALL__WGS","description":"Whole genome sequencing of up to 1500 Adult ALL diagnosis samples","abstract":"Whole genome sequencing of up to 1500 Adult ALL diagnosis samples","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004337","title":"Genomic_profiling_of_Adult_ALL__RNA","description":"RNA sequencing of up to 1500 Adult ALL diagnosis samples","abstract":"RNA sequencing of up to 1500 Adult ALL diagnosis samples","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004338","title":"Umbrella Study of MASTER/H021 data (not to be released, pool)","description":null,"abstract":"hipo_021 data pool for several publications. WES, WGS and RNA samples of different cancers. Only for internal DKFZ use, not to be released. Umbrella study.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-06T17:13:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004339","title":"Using recombinant NV/CCN3 protein in vitro to increase the stem cell activity of haematopoietic  stem cells purified from cord blood.","description":null,"abstract":"Hematopoietic Stem Cell (HSC) transplantation is an important therapy for many blood disorders, and for certain diseases it is the treatment of choice. The principal clinical source of allogeneic HSC remains bone marrow (BM), but umbilical cord blood (UCB) transplantation has the advantages of requiring less stringent cross-matching together with a lower incidence of graft versus host disease. However, UCB donations contain relatively few HSCs which limits their clinical utility, and this problem has focused attention on strategies to enhance HSC function in UCB. We have used recombinant NV/CCN3 protein in vitro to increase the stem cell activity of HSCs purified from human UCB, assessing the impact of NOV/CCN3 on the ability to xenograft immunocompromised mice and exploring various aspects of the mechanism of NOV action, including impact on gene expression.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004340","title":"Persistent STAG2 mutation  in recurrent pediatric glioblastoma","description":"Similar to their adult counterparts, the prognosis for pediatric patients with high-grade gliomas remains poor. At time of recurrence, treatment options are limited and remain without consensus. This report describes the genetic findings, obtained from whole exome sequencing of a pediatric patient with glioblastoma who underwent multiple surgical resections and treatment with standard chemoradiation, as well as a novel recombinant poliovirus vaccine therapy. Strikingly, despite the variety of treatments, there was persistence of a tumor clone, characterized by a deleterious STAG2 mutation, whose deficiency in pre-clinical studies can cause aneuploidy and aberrant mitotic progression, but remains understudied in the clinical setting. There was near elimination of an EGFR mutated and amplified tumor clone after gross total resection, standard chemoradiation, and poliovirus therapy, followed by the emergence of a persistently STAG2 mutated clone, with rare mutations in PTPN11 and BRAF, the latter composed of a novel deleterious mutation previously not reported in pediatric glioblastoma (p.D594G). This was accompanied by a mutation signature shift towards one characterized by increased DNA damage repair defects, consistent with the known underlying STAG2 deficiency. As such, this case represents a novel report following the clinical and genetic progression of a STAG2 mutated glioblastoma, including treatment with a novel and emerging immunotherapy. Although STAG2 deficiency comprises only a small subset of gliomas, this case adds clinical evidence to existing pre-clinical data supporting a role for STAG2 mutations in tumor formation and resistance to standard therapies.","abstract":"Similar to their adult counterparts, the prognosis for pediatric patients with high-grade gliomas remains poor. At time of recurrence, treatment options are limited and remain without consensus. This report describes the genetic findings, obtained from whole exome sequencing of a pediatric patient with glioblastoma who underwent multiple surgical resections and treatment with standard chemoradiation, as well as a novel recombinant poliovirus vaccine therapy. Strikingly, despite the variety of treatments, there was persistence of a tumor clone, characterized by a deleterious STAG2 mutation, whose deficiency in pre-clinical studies can cause aneuploidy and aberrant mitotic progression, but remains understudied in the clinical setting. There was near elimination of an EGFR mutated and amplified tumor clone after gross total resection, standard chemoradiation, and poliovirus therapy, followed by the emergence of a persistently STAG2 mutated clone, with rare mutations in PTPN11 and BRAF, the latter composed of a novel deleterious mutation previously not reported in pediatric glioblastoma (p.D594G). This was accompanied by a mutation signature shift towards one characterized by increased DNA damage repair defects, consistent with the known underlying STAG2 deficiency. As such, this case represents a novel report following the clinical and genetic progression of a STAG2 mutated glioblastoma, including treatment with a novel and emerging immunotherapy. Although STAG2 deficiency comprises only a small subset of gliomas, this case adds clinical evidence to existing pre-clinical data supporting a role for STAG2 mutations in tumor formation and resistance to standard therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-14T14:51:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004341","title":"Comprehensive molecular characterization of brainstem glioma","description":"Brainstem gliomas are the most devastating and lethal tumors. Survival rates are among the lowest in all cancers and options for intervention are likewise low. Due to anatomical delicacy of these areas, resection of tumors is particularly difficult and attempted resections have high perioperative mortality rates. Genomic and epigenetic studies often provide a gateway to functional studies of specific classifications of tumors that can lead to major breakthroughs in diagnosis and treatment options.","abstract":"Brainstem gliomas are the most devastating and lethal tumors. Survival rates are among the lowest in all cancers and options for intervention are likewise low. Due to anatomical delicacy of these areas, resection of tumors is particularly difficult and attempted resections have high perioperative mortality rates. Genomic and epigenetic studies often provide a gateway to functional studies of specific classifications of tumors that can lead to major breakthroughs in diagnosis and treatment options.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-14T18:09:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004342","title":"Plasma DNA profile in DNASE1L3 deficiency","description":"Plasma DNA profile in DNASE1L3 deficiency","abstract":"Plasma DNA profile in DNASE1L3 deficiency","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-15T10:24:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004343","title":"Molecular determinants of response to PD-L1 blockade across tumor types","description":"Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis lead to durable clinical responses in subsets of cancer patients across multiple indications, including non-small cell lung cancer (NSCLC), urothelial carcinoma (UC) and renal cell carcinoma (RCC). Herein, we complement PD-L1 immunohistochemistry (IHC) and tumor mutation burden (TMB) with RNA-seq in 366 patients to identify unifying and indication-specific molecular profiles that can predict response to checkpoint blockade across these tumor types. Multiple machine learning approaches failed to identify a baseline transcriptional signature highly predictive of response across these indications. Signatures described previously for immune checkpoint inhibitors also failed to validate. At the pathway level, significant heterogeneity was observed between indications, in particular within the PD-L1+ tumors. mUC and NSCLC were molecularly aligned, with cell cycle and DNA damage repair genes associated with response in PD-L1- tumors. At the gene level, the CDK4/6 inhibitor CDKN2A was identified as a significant transcriptional correlate of response, highlighting the association of non-immune pathways to the outcome of checkpoint blockade. This cross-indication analysis revealed molecular heterogeneity between mUC, NSCLC and RCC tumors, suggesting that indication-specific molecular approaches should be prioritized to formulate treatment strategies.","abstract":"Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis lead to durable clinical responses in subsets of cancer patients across multiple indications, including non-small cell lung cancer (NSCLC), urothelial carcinoma (UC) and renal cell carcinoma (RCC). Herein, we complement PD-L1 immunohistochemistry (IHC) and tumor mutation burden (TMB) with RNA-seq in 366 patients to identify unifying and indication-specific molecular profiles that can predict response to checkpoint blockade across these tumor types. Multiple machine learning approaches failed to identify a baseline transcriptional signature highly predictive of response across these indications. Signatures described previously for immune checkpoint inhibitors also failed to validate. At the pathway level, significant heterogeneity was observed between indications, in particular within the PD-L1+ tumors. mUC and NSCLC were molecularly aligned, with cell cycle and DNA damage repair genes associated with response in PD-L1- tumors. At the gene level, the CDK4/6 inhibitor CDKN2A was identified as a significant transcriptional correlate of response, highlighting the association of non-immune pathways to the outcome of checkpoint blockade. This cross-indication analysis revealed molecular heterogeneity between mUC, NSCLC and RCC tumors, suggesting that indication-specific molecular approaches should be prioritized to formulate treatment strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-15T20:11:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004344","title":"A molecular cell atlas of the human lung from single cell RNA sequencing","description":"Although single cell RNA sequencing studies have begun providing compendia of cell expression profiles, it has proven more difficult to systematically identify and localize all molecular cell types in individual organs to create a full molecular cell atlas. Here we describe droplet- and plate-based single cell RNA sequencing applied to ~75,000 human lung and blood cells, combined with a multi-pronged cell annotation approach, which have allowed us to define the gene expression profiles and anatomical locations of 58 cell populations in the human lung, including 41 of 45 previously known cell types or subtypes and 14 new ones. This comprehensive molecular atlas elucidates the biochemical functions of lung cell types and the cell-selective transcription factors and optimal markers for making and monitoring them; defines the cell targets of circulating hormones and predicts local signaling interactions including sources and targets of chemokines in immune cell trafficking and expression changes on lung homing; and identifies the cell types directly affected by lung disease genes and respiratory viruses. Comparison to mouse identified 17 molecular types that appear to have been gained or lost during lung evolution and others whose expression profiles have been substantially altered, revealing extensive plasticity of cell types and cell-type-specific gene expression during organ evolution including expression switches between cell types. This atlas provides the molecular foundation for investigating how lung cell identities, functions, and interactions are achieved in development and tissue engineering and altered in disease and evolution.","abstract":"Although single cell RNA sequencing studies have begun providing compendia of cell expression profiles, it has proven more difficult to systematically identify and localize all molecular cell types in individual organs to create a full molecular cell atlas. Here we describe droplet- and plate-based single cell RNA sequencing applied to ~75,000 human lung and blood cells, combined with a multi-pronged cell annotation approach, which have allowed us to define the gene expression profiles and anatomical locations of 58 cell populations in the human lung, including 41 of 45 previously known cell types or subtypes and 14 new ones. This comprehensive molecular atlas elucidates the biochemical functions of lung cell types and the cell-selective transcription factors and optimal markers for making and monitoring them; defines the cell targets of circulating hormones and predicts local signaling interactions including sources and targets of chemokines in immune cell trafficking and expression changes on lung homing; and identifies the cell types directly affected by lung disease genes and respiratory viruses. Comparison to mouse identified 17 molecular types that appear to have been gained or lost during lung evolution and others whose expression profiles have been substantially altered, revealing extensive plasticity of cell types and cell-type-specific gene expression during organ evolution including expression switches between cell types. This atlas provides the molecular foundation for investigating how lung cell identities, functions, and interactions are achieved in development and tissue engineering and altered in disease and evolution.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-15T20:27:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004345","title":"Multi-omics profiling of paired primary and recurrent glioblastoma patient tissues","description":"Despite maximal therapy with surgery, chemotherapy and radiotherapy, glioblastoma multiforme (GBM) patients have a median survival of only 15 months. Almost all patients inevitably experience symptomatic tumor recurrence. A hallmark of this tumor type is the large heterogeneity between patients and within tumors itself which relate to failure of standardized tumor treatment. In this study, tissue samples of paired primary and recurrent GBM tumors were investigated to identify individual factors related to tumor progression.","abstract":"Despite maximal therapy with surgery, chemotherapy and radiotherapy, glioblastoma multiforme (GBM) patients have a median survival of only 15 months. Almost all patients inevitably experience symptomatic tumor recurrence. A hallmark of this tumor type is the large heterogeneity between patients and within tumors itself which relate to failure of standardized tumor treatment. In this study, tissue samples of paired primary and recurrent GBM tumors were investigated to identify individual factors related to tumor progression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-16T09:50:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004346","title":"Whole genome bisulfite sequencing on 10 multiple myeloma cases","description":"Data quality control and adaptor-trimmed were performed with the Trimomatic tool. Paired-reads were mapped to the hg19 human reference with methylCtools aligner.","abstract":"Data quality control and adaptor-trimmed were performed with the Trimomatic tool. Paired-reads were mapped to the hg19 human reference with methylCtools aligner.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-16T09:55:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004347","title":"RNAseq on 20 samples of multiple myeloma patients and 3 normal plasma cells.","description":"RNAseq was performed using 200 ng of total RNA by GATC Biotech. Directional libraries were performed after mRNA selection by polyA selection using UTP method. RNA-seq libraries were sequenced on HiSeq2500 Illumina machine using 100bp paired-end reads. Reads alignment was performed using the STAR aligner (version 2.4.0f1) and human genome hg19 as reference.","abstract":"RNAseq was performed using 200 ng of total RNA by GATC Biotech. Directional libraries were performed after mRNA selection by polyA selection using UTP method. RNA-seq libraries were sequenced on HiSeq2500 Illumina machine using 100bp paired-end reads. Reads alignment was performed using the STAR aligner (version 2.4.0f1) and human genome hg19 as reference.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-16T09:55:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004348","title":"Enhanced reduced representation bisulfite sequencing (eRRBS) on 45 multiple myeloma samples and 3 normal plasma cell","description":"Enhanced reduced representation bisulfite sequencing (eRRBS) on 45 multiple myeloma samples and 3 normal plasma cell. Libraries were sequenced on a HiSeqTM4000 Illumina machine using 75bp paired-end reads","abstract":"Enhanced reduced representation bisulfite sequencing (eRRBS) on 45 multiple myeloma samples and 3 normal plasma cell. Libraries were sequenced on a HiSeqTM4000 Illumina machine using 75bp paired-end reads","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-16T09:55:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004349","title":"Alternative lengthening of telomeres in childhood neuroblastoma from genome to proteome","description":"Telomere maintenance by telomerase activation or alternative lengthening of telomeres (ALT) is a major determinant of poor outcome in neuroblastoma. Here, we screen for ALT in primary and relapsed neuroblastomas and characterize its features using multi-omics profiling. We aim to deepen the knowledge about the biology and clinical features of ALT-positive neuroblastomas by enriching ALT tumors in the study cohort independent of ATRX mutation status. Using a combination of genomic, transcriptomic and proteomic profiling, we provide evidence that this subgroup is clinically and molecularly distinct.","abstract":"Telomere maintenance by telomerase activation or alternative lengthening of telomeres (ALT) is a major determinant of poor outcome in neuroblastoma. Here, we screen for ALT in primary and relapsed neuroblastomas and characterize its features using multi-omics profiling. We aim to deepen the knowledge about the biology and clinical features of ALT-positive neuroblastomas by enriching ALT tumors in the study cohort independent of ATRX mutation status. Using a combination of genomic, transcriptomic and proteomic profiling, we provide evidence that this subgroup is clinically and molecularly distinct.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-16T13:43:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004350","title":"Effects_of_Chemotherapy_on_the_Somatic_Mutational_Landscape_in_Normal_Human_Tissue_WES_H38","description":"This study is investigating the effects of chemotherapy drugs used in cancer treatment on the somatic mutational landscape in normal human tissues. The samples used in this study have been taken from rapid autopsies of patients who have undergone chemotherapy using drugs thought to cause mutations in the DNA. Structures from a variety of tissues will be dissected using LCM and whole genome sequences will be produced in order to assess mutational burdens and signatures.","abstract":"This study is investigating the effects of chemotherapy drugs used in cancer treatment on the somatic mutational landscape in normal human tissues. The samples used in this study have been taken from rapid autopsies of patients who have undergone chemotherapy using drugs thought to cause mutations in the DNA. Structures from a variety of tissues will be dissected using LCM and whole genome sequences will be produced in order to assess mutational burdens and signatures.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004351","title":"Effects_of_Chemotherapy_on_the_Somatic_Mutational_Landscape_in_Normal_Human_Tissue_WGS_H38","description":"This study is investigating the effects of chemotherapy drugs used in cancer treatment on the somatic mutational landscape in normal human tissues. The samples used in this study have been taken from rapid autopsies of patients who have undergone chemotherapy using drugs thought to cause mutations in the DNA. Structures from a variety of tissues will be dissected using LCM and whole genome sequences will be produced in order to assess mutational burdens and signatures.","abstract":"his study is investigating the effects of chemotherapy drugs used in cancer treatment on the somatic mutational landscape in normal human tissues. The samples used in this study have been taken from rapid autopsies of patients who have undergone chemotherapy using drugs thought to cause mutations in the DNA. Structures from a variety of tissues will be dissected using LCM and whole genome sequences will be produced in order to assess mutational burdens and signatures.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004352","title":"Epigenomic profile of diverse cancer","description":"Epigenomic profile of diverse cancer.","abstract":"Epigenomic profile of diverse cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-17T17:59:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004353","title":"Molecular subsets in renal cancer determine outcome to checkpoint and angiogenesis blockade","description":"We conducted integrated multi-omics evaluation of 823 tumors from advanced renal cell carcinoma (RCC) patients and identified molecular subsets associated with differential clinical outcomes to angiogenesis blockade alone or with a checkpoint inhibitor. Unsupervised transcriptomic analysis revealed six molecular subsets with distinct angiogenesis, immune, cell cycle, metabolism, and stromal programs. While sunitinib was effective in subsets with high angiogenesis, atezolizumab+bevacizumab improved clinical benefit in tumors with high T-effector and/or cell cycle transcription. Somatic mutations in PBRM1 and KDM5C associated with high angiogenesis and AMPK/Fatty acid oxidation gene expression, while CDKN2A/B and TP53 alterations were more prevalent in tumors with increased cell cycle and anabolic metabolism. Sarcomatoid tumors exhibited low prevalence of PBRM1 mutations and angiogenesis markers, frequent CDKN2A/B, BAP1 and TP53 alterations, and increased PD-L1 expression. These findings can be applied to molecularly stratify advanced RCC patients, explain improved outcomes of sarcomatoid tumors to checkpoint blockade, and develop personalized therapies.","abstract":"We conducted integrated multi-omics evaluation of 823 tumors from advanced renal cell carcinoma (RCC) patients and identified molecular subsets associated with differential clinical outcomes to angiogenesis blockade alone or with a checkpoint inhibitor. Unsupervised transcriptomic analysis revealed six molecular subsets with distinct angiogenesis, immune, cell cycle, metabolism, and stromal programs. While sunitinib was effective in subsets with high angiogenesis, atezolizumab+bevacizumab improved clinical benefit in tumors with high T-effector and/or cell cycle transcription. Somatic mutations in PBRM1 and KDM5C associated with high angiogenesis and AMPK/Fatty acid oxidation gene expression, while CDKN2A/B and TP53 alterations were more prevalent in tumors with increased cell cycle and anabolic metabolism. Sarcomatoid tumors exhibited low prevalence of PBRM1 mutations and angiogenesis markers, frequent CDKN2A/B, BAP1 and TP53 alterations, and increased PD-L1 expression. These findings can be applied to molecularly stratify advanced RCC patients, explain improved outcomes of sarcomatoid tumors to checkpoint blockade, and develop personalized therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-17T19:25:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004354","title":"H3.3G34W promotes growth and impedes differentiation of osteoblast-like mesenchymal progenitors in Giant Cell Tumour of the Bone","description":null,"abstract":"Glycine 34 to tryptophan (G34W) substitutions in H3.3 arise in ~90% of giant-cell tumours of bone (GCT). Here, we comprehensively characterize the epigenetic, transcriptomic and secreted proteomic profiles of patient samples and tumour-derived cells CRISPR/Cas9 edited for G34W. We show this mutation is necessary for tumour initiation and maintenance. G34W-induced H3.3K36me3 loss on mutant H3.3 shifts genome-wide the repressive H3K27me3 mark from intergenic to genic regions, promoting the redistribution of other chromatin marks and aberrant transcription, which alter cell fate and identity in mesenchymal progenitors. Single-cell transcriptomics reveals that G34W stromal cells resemble osteoblast progenitors with a neoplastic trajectory from an SPP1+IBSP+ osteoblast-like population towards an ACTA2+ contractile population, which secretes extracellular matrix ligands predicted to activate osteoclasts and recruit giant-cells. Our findings suggest that G34W leads to GCT by sustaining a transformed state in osteoblast-like progenitors, which promotes neoplastic growth, recruitment of pathological giant osteoclasts, and bone destruction.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004355","title":"Cell-free DNA fragmentation patterns and personalized sequencing reveal circulating tumor DNA in urine and plasma of glioma patients","description":"Glioma-derived cell-free DNA (cfDNA) is challenging to detect using liquid biopsy as levels in body fluids are low.\nWe determined the glioma-derived DNA fractions in tumor biopsies, in cerebrospinal fluid (CSF), plasma and urine samples, using deep sequencing of personalized capture panels. By sequencing cfDNA across thousands of mutations identified individually in each patient’s matched tumor we detected tumor-derived DNA in plasma (10/12) and urine samples (8/11). The median tumor fraction was 6.4x10-3 in CSF, 3.1x10-5 in plasma and 4.7x10-5 in urine. We identified a shift in the size distribution for mutant cfDNA fragments in these body fluids.\nNext, we analyzed cfDNA fragment sizes with paired-end shallow whole genome sequencing (WGS) in urine samples from 35 patients with gliomas, 8 individuals with non-malignant brain disorders, and 26 controls (n=69 individuals, 96 samples). cfDNA in urine of glioma patients was significantly more fragmented compared to urine from patients with non-malignant brain disorders (t-test, p=1.7x10-2) and compared to urine of controls (t-test, p=5.2x10-9). The proportion of DNA fragments &lt;60 bp was higher in glioma patients urine and could be used for classification (AUC=0.93). Machine learning models integrating fragment lengths could identify urine samples from glioma patients (AUC=0.97 in cross-validation).","abstract":"Glioma-derived cell-free DNA (cfDNA) is challenging to detect using liquid biopsy as levels in body fluids are low.\nWe determined the glioma-derived DNA fractions in tumor biopsies, in cerebrospinal fluid (CSF), plasma and urine samples, using deep sequencing of personalized capture panels. By sequencing cfDNA across thousands of mutations identified individually in each patient’s matched tumor we detected tumor-derived DNA in plasma (10/12) and urine samples (8/11). The median tumor fraction was 6.4x10-3 in CSF, 3.1x10-5 in plasma and 4.7x10-5 in urine. We identified a shift in the size distribution for mutant cfDNA fragments in these body fluids.\nNext, we analyzed cfDNA fragment sizes with paired-end shallow whole genome sequencing (WGS) in urine samples from 35 patients with gliomas, 8 individuals with non-malignant brain disorders, and 26 controls (n=69 individuals, 96 samples). cfDNA in urine of glioma patients was significantly more fragmented compared to urine from patients with non-malignant brain disorders (t-test, p=1.7x10-2) and compared to urine of controls (t-test, p=5.2x10-9). The proportion of DNA fragments &lt;60 bp was higher in glioma patients urine and could be used for classification (AUC=0.93). Machine learning models integrating fragment lengths could identify urine samples from glioma patients (AUC=0.97 in cross-validation).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-20T11:10:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004356","title":"Phylogenetic reconstruction of breast cancer","description":"The aim of this study was to identify the evolutionary trajectories of metastatic breast cancer. We present whole genome sequencing data (primary tumours, axillary lymph nodes, distant metastasis and matched normal tissues) from 16 breast cancer patients. This work sheds light on the routes on which tumour cells metastasize and their role in disease progression in ER-positive breast cancer.","abstract":"The aim of this study was to identify the evolutionary trajectories of metastatic breast cancer. We present whole genome sequencing data (primary tumours, axillary lymph nodes, distant metastasis and matched normal tissues) from 16 breast cancer patients. This work sheds light on the routes on which tumour cells metastasize and their role in disease progression in ER-positive breast cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-20T12:45:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004357","title":"Whole-exome sequencing of extranodal NK/T cell lymphoma","description":"Extranodal NK/T cell lymphoma (ENKTCL) is an aggressive Epstein-Barr virus-associated T/NK neoplasm that predominantly affects Asians. To explore the causative somatic events, we conducted a comprehensive genetic analysis of 19 ENKTCL patients including whole-exome sequencing (N = 16). Commonly deregulated gene pathways in ENKTCL included epigenetic modifiers followed by human leukocyte antigen (HLA) and related genes and JAK-STAT pathway.","abstract":"Extranodal NK/T cell lymphoma (ENKTCL) is an aggressive Epstein-Barr virus-associated T/NK neoplasm that predominantly affects Asians. To explore the causative somatic events, we conducted a comprehensive genetic analysis of 19 ENKTCL patients including whole-exome sequencing (N = 16). Commonly deregulated gene pathways in ENKTCL included epigenetic modifiers followed by human leukocyte antigen (HLA) and related genes and JAK-STAT pathway.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-20T19:41:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004358","title":"RNA-sequencing of Non-muscle Invasive Bladder cancer (NMIBC)","description":"This RNA-sequencing cohort includes 78 Non-muscle Invasive Bladder cancer (NMIBC) samples and 7 Muscle Invasive Bladder cancer (MIBC) samples.","abstract":"This RNA-sequencing cohort includes 78 Non-muscle Invasive Bladder cancer (NMIBC) samples and 7 Muscle Invasive Bladder cancer (MIBC) samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-20T23:08:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004359","title":"Sequencing of an adolescent patient with germline RET mutant alveolar rhabdomyosarcoma","description":"An adolescent patient presented with an alveolar rhabdomyosarcoma made more unique by the presence of a germline RET mutation ordinarily associated with and a known driver of multiple endocrine neoplasia type 2A (MEN2A) cancer. To better understand the role of this germline RET mutation in the genetics and phenotypic response of this unique alveolar rhabdomyosarcoma, we performed DNA and RNA sequencing of the patients in addition to functional studies on patient-derived cultures and genetically similar similar cell models.","abstract":"An adolescent patient presented with an alveolar rhabdomyosarcoma made more unique by the presence of a germline RET mutation ordinarily associated with and a known driver of multiple endocrine neoplasia type 2A (MEN2A) cancer. To better understand the role of this germline RET mutation in the genetics and phenotypic response of this unique alveolar rhabdomyosarcoma, we performed DNA and RNA sequencing of the patients in addition to functional studies on patient-derived cultures and genetically similar similar cell models.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-20T23:56:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004360","title":"geneseeq test","description":"just a test","abstract":"just a test","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004361","title":"TP53 variant detection analysis in high grade serous epithelial ovarian cancer","description":"The aim of this study was to detect in the DNA purified from PAP test samples collected years before the diagnosis of high grade serous epithelial ovarian cancer the presence of the clonal pathogenic TP53 variant identified in the matched primary tumor biopsy.  In this specific part of the study, we analyzed FFPE tumor samples to identify clonal pathogenic variants to be tested in matched PAP tests.","abstract":"The aim of this study was to detect in the DNA purified from PAP test samples collected years before the diagnosis of high grade serous epithelial ovarian cancer the presence of the clonal pathogenic TP53 variant identified in the matched primary tumor biopsy.  In this specific part of the study, we analyzed FFPE tumor samples to identify clonal pathogenic variants to be tested in matched PAP tests.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-21T09:21:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004362","title":"Genetic diversity and continuity of the population of the UAE","description":"With high consanguinity rates on the Arabian Peninsula, it would not have been unexpected if the population of the UAE was shown to be relatively homogenous.  However, this study of 1,000 UAE nationals, provided a contrasting perspective, one of a relatively heterogeneous population. Located at the apex of Europe, Asia and Africa, the observed diversity could be explained by a plethora of migration patterns since the first Out-of-Africa movement. A strategy to explore the extent of genetic variation of the population of the UAE is presented.  The first step involved a comprehensive population stratification study that was instructive for subsequent Whole Genome Sequencing (WGS) of suitable representatives (which is described elsewhere). When this UAE data was compared to previous smaller studies from the region, the findings were consistent with a population that is a diverse and admixed group of people.  However, rather than sharp and distinctive clusters, a continuous genotype distribution was observed.  The analysis showed a continuous gradient of ancestral populations, suggesting that admixture on the south eastern tip of Arabian Peninsula occurred gradually.  When visualized using a unique technique that combined admixture ratios and Principal Component Analysis (PCA), unappreciated diversity was revealed while mitigating projection bias of conventional PCA. The analytical strategy used here highlights the complementary nature of data from genotype array and WGS for anthropological studies.  Specifically, genotype array data was instructive to select representative subjects for WGS.  Furthermore, from the 2.3 million allele frequencies obtained from genotype arrays, we identified 46,481 loci with allele frequencies that were significantly different with respect to other world populations. This comparison of allele frequencies facilitates variant prioritization in common diseases. In addition, these loci bear great potential as biomarkers in anthropological and forensic studies.","abstract":"With high consanguinity rates on the Arabian Peninsula, it would not have been unexpected if the population of the UAE was shown to be relatively homogenous.  However, this study of 1,000 UAE nationals, provided a contrasting perspective, one of a relatively heterogeneous population. Located at the apex of Europe, Asia and Africa, the observed diversity could be explained by a plethora of migration patterns since the first Out-of-Africa movement. A strategy to explore the extent of genetic variation of the population of the UAE is presented.  The first step involved a comprehensive population stratification study that was instructive for subsequent Whole Genome Sequencing (WGS) of suitable representatives (which is described elsewhere). When this UAE data was compared to previous smaller studies from the region, the findings were consistent with a population that is a diverse and admixed group of people.  However, rather than sharp and distinctive clusters, a continuous genotype distribution was observed.  The analysis showed a continuous gradient of ancestral populations, suggesting that admixture on the south eastern tip of Arabian Peninsula occurred gradually.  When visualized using a unique technique that combined admixture ratios and Principal Component Analysis (PCA), unappreciated diversity was revealed while mitigating projection bias of conventional PCA. The analytical strategy used here highlights the complementary nature of data from genotype array and WGS for anthropological studies.  Specifically, genotype array data was instructive to select representative subjects for WGS.  Furthermore, from the 2.3 million allele frequencies obtained from genotype arrays, we identified 46,481 loci with allele frequencies that were significantly different with respect to other world populations. This comparison of allele frequencies facilitates variant prioritization in common diseases. In addition, these loci bear great potential as biomarkers in anthropological and forensic studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-21T09:57:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004363","title":"Comprehensive Genomic Characterization of Refractory Multiple Myeloma Reveals a Complex Mutational and Structural Landscape Associated with Drug Resistance (H067)","description":"Outcome of patients with multiple myeloma (MM) refractory to immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs) is still very poor. To elucidate the genetic landscape of relapsed/refractory MM (RRMM) we performed whole genome and transcriptome sequencing of 39 heavily pretreated RRMM patients with at least double refractoriness revealing complex structural changes and a high mutational load (H067/K08K). We found a median of 67 structural variants and 116 nonsynonymous exonic mutations per patient. Assessment of oncogenic drivers showed NRAS, BRAF, TP53, KRAS, SLC4A7, FAM46C, DIS3, RB1, KMT2C, MLLT4, EWSR1, HCFC2, and COPS3 as significantly mutated. We found multiple genomic regions with bi-allelic events affecting known tumor suppressor genes, most frequently TP53, RB1, and TRAF3. Supervised analysis of mutational signatures showed a major contribution of Cosmic signature 6 associated with deficiency in DNA mismatch repair and the ‘BRCAness’ signature which coincided with mutations in genes known to confer PARP inhibitor sensitivity. Recurrently mutated gene networks included genes with relevance for PI and IMiD activity, the latter including in particular members of the Cereblon and the COP9 signalosome complex. In conclusion, this comprehensive genomic characterization revealed a complex mutational and structural landscape in RRMM and highlights potential implications for therapeutic strategies.","abstract":"Outcome of patients with multiple myeloma (MM) refractory to immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs) is still very poor. To elucidate the genetic landscape of relapsed/refractory MM (RRMM) we performed whole genome and transcriptome sequencing of 39 heavily pretreated RRMM patients with at least double refractoriness revealing complex structural changes and a high mutational load (H067/K08K). We found a median of 67 structural variants and 116 nonsynonymous exonic mutations per patient. Assessment of oncogenic drivers showed NRAS, BRAF, TP53, KRAS, SLC4A7, FAM46C, DIS3, RB1, KMT2C, MLLT4, EWSR1, HCFC2, and COPS3 as significantly mutated. We found multiple genomic regions with bi-allelic events affecting known tumor suppressor genes, most frequently TP53, RB1, and TRAF3. Supervised analysis of mutational signatures showed a major contribution of Cosmic signature 6 associated with deficiency in DNA mismatch repair and the ‘BRCAness’ signature which coincided with mutations in genes known to confer PARP inhibitor sensitivity. Recurrently mutated gene networks included genes with relevance for PI and IMiD activity, the latter including in particular members of the Cereblon and the COP9 signalosome complex. In conclusion, this comprehensive genomic characterization revealed a complex mutational and structural landscape in RRMM and highlights potential implications for therapeutic strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-21T10:11:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004364","title":"Whole-genome sequencing of rare disease patients in a national healthcare system","description":"Most patients with rare diseases do not receive a molecular diagnosis and the aetiologicalvariants and mediating genes for more than half such disorders remain to be discovered. Weimplemented whole-genome sequencing (WGS) in a national healthcare system to streamlinediagnosis and to discover unknown aetiological variants, in the coding and non-coding regionsof the genome. In a pilot study for the 100,000 Genomes Project, we generated WGS data for13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to1,138 of the 7,065 patients with detailed phenotypic data. We identified 95 Mendelianassociations between genes and rare diseases, of which 11 have been discovered since 2015and at least 79 are confirmed aetiological. Using WGS of UK Biobank1, we showed that rarealleles can explain the presence of some individuals in the tails of a quantitative red blood cell(RBC) trait. Finally, we reported 4 novel non-coding variants which cause disease through thedisruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates asynergy by using WGS for diagnosis and aetiological discovery in routine healthcare.","abstract":"Most patients with rare diseases do not receive a molecular diagnosis and the aetiologicalvariants and mediating genes for more than half such disorders remain to be discovered. Weimplemented whole-genome sequencing (WGS) in a national healthcare system to streamlinediagnosis and to discover unknown aetiological variants, in the coding and non-coding regionsof the genome. In a pilot study for the 100,000 Genomes Project, we generated WGS data for13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to1,138 of the 7,065 patients with detailed phenotypic data. We identified 95 Mendelianassociations between genes and rare diseases, of which 11 have been discovered since 2015and at least 79 are confirmed aetiological. Using WGS of UK Biobank1, we showed that rarealleles can explain the presence of some individuals in the tails of a quantitative red blood cell(RBC) trait. Finally, we reported 4 novel non-coding variants which cause disease through thedisruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates asynergy by using WGS for diagnosis and aetiological discovery in routine healthcare.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-21T14:34:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004365","title":"Candidate Gene Case Control Study of Human African Trypanosomiasis in the Democratic Republic of Congo","description":null,"abstract":"Human African trypanosomiasis (HAT) is a protozoal disease transmitted by bites of tsetse flies. Infection with trypanosomes can lead directly to active HAT or latent infection with no detectable parasites, which may progress to active HAT or to spontaneous self-cure. Genetic variation could explain these differences in the outcome of infection. To test this hypothesis, 96 polymorphisms in 17 candidate genes were tested for association with phenotype in a case control design. The genes tested were: APOL1, CFH, HLA-A, HPR, HP, IL1B, IL12B, IL12RB1, IL10, IL4R, MIF ,TNFA, IL6, IL4, IL8, IFNG, and HLA-G.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-21T15:05:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004366","title":"Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome","description":"Endometrioid ovarian carcinoma (EnOC) is an under-investigated type of ovarian carcinoma. Here, we report the largest genomic study of EnOCs to date, performing whole exome sequencing of 112 cases following rigorous pathological assessment. High frequencies of mutation were detected in CTNNB1(43%), PIK3CA(43%), ARID1A(36%), PTEN(29%), TP53(26%) and SOX8(19%), a novel target of recurrent mutation in EnOC. POLE and mismatch repair protein-encoding genes were mutated at lower frequency (6%, 18%) with significant co-occurrence. A molecular taxonomy was constructed using a novel algorithm (PRISTINE), identifying clinically distinct EnOC subtypes: TP53m cases demonstrated greater genomic complexity, were frequently FIGO stage III/IV at diagnosis (48%) and incompletely debulked (44%), and demonstrated inferior survival; conversely, CTNNB1m cases demonstrated low complexity and excellent clinical outcome, were predominantly stage I/II at diagnosis (89%) and completely resected (87%). Tumour complexity provides further resolution within the TP53wt/CTNNB1wt group. Moreover, we identify the WNT, MAPK/RAS and PI3K pathways as good candidate targets for molecular therapeutics in EnOC.","abstract":"Endometrioid ovarian carcinoma (EnOC) is an under-investigated type of ovarian carcinoma. Here, we report the largest genomic study of EnOCs to date, performing whole exome sequencing of 112 cases following rigorous pathological assessment. High frequencies of mutation were detected in CTNNB1(43%), PIK3CA(43%), ARID1A(36%), PTEN(29%), TP53(26%) and SOX8(19%), a novel target of recurrent mutation in EnOC. POLE and mismatch repair protein-encoding genes were mutated at lower frequency (6%, 18%) with significant co-occurrence. A molecular taxonomy was constructed using a novel algorithm (PRISTINE), identifying clinically distinct EnOC subtypes: TP53m cases demonstrated greater genomic complexity, were frequently FIGO stage III/IV at diagnosis (48%) and incompletely debulked (44%), and demonstrated inferior survival; conversely, CTNNB1m cases demonstrated low complexity and excellent clinical outcome, were predominantly stage I/II at diagnosis (89%) and completely resected (87%). Tumour complexity provides further resolution within the TP53wt/CTNNB1wt group. Moreover, we identify the WNT, MAPK/RAS and PI3K pathways as good candidate targets for molecular therapeutics in EnOC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-21T15:44:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004367","title":"Skeletal muscle transcriptomic comparison between long-term trained and untrained men and women","description":"Published study:\nhttps://www.cell.com/cell-reports/fulltext/S2211-1247(20)30789-0\n\nTo investigate the influence of lifelong exercise training on human metabolism, we generated global skeletal muscle transcriptomic data from long-term endurance (9 men, 9 women) and strength (7 men) trained individuals. These data were compared with healthy age-matched untrained controls (7 men, 8 women).","abstract":"Published study:\nhttps://www.cell.com/cell-reports/fulltext/S2211-1247(20)30789-0\n\nTo investigate the influence of lifelong exercise training on human metabolism, we generated global skeletal muscle transcriptomic data from long-term endurance (9 men, 9 women) and strength (7 men) trained individuals. These data were compared with healthy age-matched untrained controls (7 men, 8 women).","study_type":"Other","pubmed_ids":[32579934],"external_links":null,"is_released":true,"released_date":"2020-04-22T08:38:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004368","title":"STM3 - Mouliere et al, 2018. Enhanced detection of circulating tumor DNA by fragment size analysis","description":null,"abstract":"Enhanced detection of circulating tumor DNA by fragment size analysis.\nMouliere et al, 2018\nThis submission contains all non-ovarian and non-normal/healthy data (see separate submission for these)","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004369","title":"scRNA-seq data of BALF and blood cells from COPD and control","description":"Chronic obstructive pulmonary disease (COPD) is ranked the third leading cause of death worldwide and hence constitutes a significant burden, both medically and financially. To date, the cellular mechanism underlying COPD is poorly understood and thus no effective therapy is currently available. To broaden the current knowledge of the immune landscape in the alveolar space, we performed scRNA-Seq of CD45-enriched bronchoalveolar lavage fluid (BALF) cells and isolated blood leukocytes obtained from COPD patients and healthy controls using both the Seq-Well and the Chromium (10x Genomics) technology.","abstract":"Chronic obstructive pulmonary disease (COPD) is ranked the third leading cause of death worldwide and hence constitutes a significant burden, both medically and financially. To date, the cellular mechanism underlying COPD is poorly understood and thus no effective therapy is currently available. To broaden the current knowledge of the immune landscape in the alveolar space, we performed scRNA-Seq of CD45-enriched bronchoalveolar lavage fluid (BALF) cells and isolated blood leukocytes obtained from COPD patients and healthy controls using both the Seq-Well and the Chromium (10x Genomics) technology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-22T13:09:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004370","title":"Epigenetic analyses of methylation and nucleosome occupancy in cell-free DNA (cfNOMe)","description":"Cell-free DNA (cfDNA) has become essential in cancer diagnostics and prenatal testing. We investigate enzymatic cytosine conversion for epigenetic analyses of cfDNA and find that it reliably measures cytosine methylation and nucleosome occupancy. Whereas previously, separate experiments had to be performed to study either epigenetic marking, this approach delivers reliable results for both, enabling more comprehensive and inexpensive epigenetic profiling of cfDNA.","abstract":"Cell-free DNA (cfDNA) has become essential in cancer diagnostics and prenatal testing. We investigate enzymatic cytosine conversion for epigenetic analyses of cfDNA and find that it reliably measures cytosine methylation and nucleosome occupancy. Whereas previously, separate experiments had to be performed to study either epigenetic marking, this approach delivers reliable results for both, enabling more comprehensive and inexpensive epigenetic profiling of cfDNA.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-22T14:49:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004371","title":"Whole exome sequencing identifies clinically relevant mutational signatures in resected hepatocellular carcinoma","description":"We conducted a multicentre pilot study on patients with localized HCC following complete radiological response to surgical resection. Patients received 250 mg oral gefitinib once daily as adjuvant therapy, up to a maximum of 6 months. The clinical endpoints included recurrence-free survival (RFS) and overall survival (OS), and correlative genetic analyses were conducted from whole exome sequencing data (n=33). All statistical analyses were carried out on an intention-to-treat basis. The study is registered with ClinicalTrials.gov (NCT00282100).","abstract":"We conducted a multicentre pilot study on patients with localized HCC following complete radiological response to surgical resection. Patients received 250 mg oral gefitinib once daily as adjuvant therapy, up to a maximum of 6 months. The clinical endpoints included recurrence-free survival (RFS) and overall survival (OS), and correlative genetic analyses were conducted from whole exome sequencing data (n=33). All statistical analyses were carried out on an intention-to-treat basis. The study is registered with ClinicalTrials.gov (NCT00282100).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-22T16:15:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004372","title":"Feasibility and safety of a multi-cancer blood test for screening and intervention","description":"We evaluated the feasibility and safety of blood testing for cancer in an interventional study of 10,006 women. Positive tests for DNA or protein were independently confirmed and diagnostic PET-CT imaging was used to localize disease. During the study, 26 cancers were first detected by blood testing, 24 more by standard-of-care screening, and 46 by neither approach. Surgicalexcision of the primary tumors was performed on 12 cancers first detected by blood testing.1.0% of participants underwent PET-CT imaging based on false positive blood tests, and 0.22% underwent a futile invasive diagnostic procedure. These data demonstrate that multi-cancer blood testing, when followed by PET-CT localization, can be safely incorporated into routineclinical care, in some cases leading to surgery with intent to cure. Further studies will be required to determine the clinical validity and utility of multi-cancer blood testing.","abstract":"We evaluated the feasibility and safety of blood testing for cancer in an interventional study of 10,006 women. Positive tests for DNA or protein were independently confirmed and diagnostic PET-CT imaging was used to localize disease. During the study, 26 cancers were first detected by blood testing, 24 more by standard-of-care screening, and 46 by neither approach. Surgicalexcision of the primary tumors was performed on 12 cancers first detected by blood testing.1.0% of participants underwent PET-CT imaging based on false positive blood tests, and 0.22% underwent a futile invasive diagnostic procedure. These data demonstrate that multi-cancer blood testing, when followed by PET-CT localization, can be safely incorporated into routineclinical care, in some cases leading to surgery with intent to cure. Further studies will be required to determine the clinical validity and utility of multi-cancer blood testing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-22T19:55:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004373","title":"Sensitive detection of tumor mutations from blood and its application to immunotherapy prognosis","description":"Cell-free DNA (cfDNA) is attractive for many applications, including cancer detection, locating, and monitoring. A fundamental task underlying these applications is the SNV calling from cfDNA, which, however, faces a new challenge, namely, the generally very low tumor content in cfDNA. Thus all existing callers fail to achieve satisfactory performance. Here we present cfSNV, a method incorporating multi-layer error suppression and hierarchical mutation calling, to address this important challenge. Furthermore, by leveraging cfDNA’s  comprehensive coverage of clonal landscape, for the first time cfSNV can profile mutations even in subclones. In both simulated and real patient data, cfSNV vastly outperforms existing tools, showing tens of times increase in sensitivity in detecting mutations with low allele frequency while maintaining high precision. cfSNV can enhance the clinical utilities of cfDNA by dramatically reducing the required sequencing depth and therefore reduce the cost by magnitudes, and further make the Whole-Exome-Sequencing of cfDNA a viable option.  As an example, we demonstrate that cfDNA-WES allows a new biomarker to effectively select patients for immunotherapy.","abstract":"Cell-free DNA (cfDNA) is attractive for many applications, including cancer detection, locating, and monitoring. A fundamental task underlying these applications is the SNV calling from cfDNA, which, however, faces a new challenge, namely, the generally very low tumor content in cfDNA. Thus all existing callers fail to achieve satisfactory performance. Here we present cfSNV, a method incorporating multi-layer error suppression and hierarchical mutation calling, to address this important challenge. Furthermore, by leveraging cfDNA’s  comprehensive coverage of clonal landscape, for the first time cfSNV can profile mutations even in subclones. In both simulated and real patient data, cfSNV vastly outperforms existing tools, showing tens of times increase in sensitivity in detecting mutations with low allele frequency while maintaining high precision. cfSNV can enhance the clinical utilities of cfDNA by dramatically reducing the required sequencing depth and therefore reduce the cost by magnitudes, and further make the Whole-Exome-Sequencing of cfDNA a viable option.  As an example, we demonstrate that cfDNA-WES allows a new biomarker to effectively select patients for immunotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-23T03:03:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004374","title":"Single cell characterization of arrested B-lymphoid differentiation and leukemic cell states in ETV6-RUNX1-positive pediatric leukemia","description":null,"abstract":"Genetic hits in the gene regulatory network underlie arrested lymphoid cell differentiation and emergence of the most common childhood cancer, acute lymphoblastic leukemia (ALL). Here, we aimed to understand what alterations in the lymphoid gene expression program arise in leukemias carrying the common translocation t12;21, fusing the ETV6 and RUNX1 genes. We compared normal B-lineage differentiation and in vivo leukemic cell states at diagnosis and during chemotherapy using single cell RNA-sequencing (scRNA-seq) and several complementary genomics assays. We show that noisy gene expression of critical pre-BCR signaling pathway genes arises as a consequence of ETV6-RUNX1-mediated repression of intronic enhancers. Furthermore, our analysis implicated the genome-wide association study hit ELK3 among high activity transcription factors in leukemic cell states. The accompanying gene expression changes were found to associate with natural killer cell inactivation and depletion in the leukemic immune microenvironment. Moreover, our results suggest that the abundance of G1 cell cycle state at diagnosis and lack of differentiation-associated regulatory network changes represent features of chemoresistance during induction chemotherapy. Finally, we show that selective inhibitors of ETS-transcription factors could dramatically reduce cell viability. In summary, our results provide a detailed picture of gene regulatory defects in leukemic bone marrow, disclosing mechanistic insight on the role of gene expression noise and suggesting new treatment strategies targeting the active regulatory network.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-23T09:01:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004375","title":"RNA-seq of human embryonic heart, lung, and cerebellum","description":"Characterization of cell types in the human embronic heart, lung, and cerebellum.","abstract":"Characterization of cell types in the human embronic heart, lung, and cerebellum.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-23T09:42:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004376","title":"OSCC WES + WGS Boot et al. 2020","description":null,"abstract":"Whole exome sequencing of 18 tumor-normal pairs and whole-genome sequencing of 2 tumor-normal pairs with the aim of identifying novel mutational signatures.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-24T07:15:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004377","title":"OSCC WES + WGS","description":null,"abstract":"WES (N=18) and WGS (N=2) of OSCC tumors and normals with the aim of identifying novel mutational signatures in Asian tumors","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004378","title":"MDS recurrent mutations in MM patients","description":null,"abstract":"To establish the relationship between the presence of MDS-PA and clonal hematopoiesis, we used a FACSAria II flow cytometer (BD) to sort CD34+ hematopoietic progenitor cells (HPCs) from 67 patients (with (N = 26) or without MDS-PA (N = 41)). The TruSight™ myeloid targeted sequencing panel (Illumina, USA) and a customized PAN-Myeloid panel (SOPHiA GENETICS, Switzerland) were used to detect MDS-associated single nucleotide variants. A total of six samples (CD34+ HPCs as well as altered neutrophils and monocytes isolated by FACS) from 4 patients with MDS-PA were analyzed using a new single-cell DNA sequencing technology,Tapestri® (Mission Bio).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004379","title":"Whole genome sequencing of glioblastoma reveals enrichment of non-coding constraint mutations in known and novel genes","description":"Glioblastoma (GBM) has one of the worst five-year survival rates of all cancers. While genomic studies of the disease have been performed, alterations in the non-coding regulatory regions of GBM have largely remained unexplored. We apply whole-genome sequencing (WGS) to identify non-coding mutations, with regulatory potential in GBM, under the hypothesis that regions of evolutionary constraint are likely to be functional, and somatic mutations are likely more damaging than in unconstrained regions.","abstract":"Glioblastoma (GBM) has one of the worst five-year survival rates of all cancers. While genomic studies of the disease have been performed, alterations in the non-coding regulatory regions of GBM have largely remained unexplored. We apply whole-genome sequencing (WGS) to identify non-coding mutations, with regulatory potential in GBM, under the hypothesis that regions of evolutionary constraint are likely to be functional, and somatic mutations are likely more damaging than in unconstrained regions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-26T17:28:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004380","title":"Accurate mapping of mitochondrial DNA deletions and duplications using deep sequencing","description":"Deletions and duplications in mitochondrial DNA (mtDNA) cause mitochondrial disease and accumulate in conditions such as cancer and age-related disorders, but validated high-throughput methodology that can readily detect and discriminate between these two types of events is lacking. Here we present MitoSAlt, a computational method for accurate identification, quantification and visualization of mtDNA deletions and duplications from whole genome, whole exome or transcriptome sequencing data. MitoSAlt was tested on simulated sequencing reads and human patient samples with single deletions and duplications to verify its accuracy. Application to mouse models of mtDNA maintenance disease further demonstrated the ability to detect deletions and duplications even at low levels of heteroplasmy. MitoSAlt paves the way for simple and reliable determination of mtDNA deletions and duplications across a wide range of relevant conditions and available sequencing datasets.\n ","abstract":"Deletions and duplications in mitochondrial DNA (mtDNA) cause mitochondrial disease and accumulate in conditions such as cancer and age-related disorders, but validated high-throughput methodology that can readily detect and discriminate between these two types of events is lacking. Here we present MitoSAlt, a computational method for accurate identification, quantification and visualization of mtDNA deletions and duplications from whole genome, whole exome or transcriptome sequencing data. MitoSAlt was tested on simulated sequencing reads and human patient samples with single deletions and duplications to verify its accuracy. Application to mouse models of mtDNA maintenance disease further demonstrated the ability to detect deletions and duplications even at low levels of heteroplasmy. MitoSAlt paves the way for simple and reliable determination of mtDNA deletions and duplications across a wide range of relevant conditions and available sequencing datasets.\n ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-27T09:41:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004381","title":"scRNA-seq of HSPC treated with gemcitabine and carbplatin","description":"The study used cryopreserved hematopoietic stem and progenitor cells (HSPCs) harvested from one patient with chronic myelogenous leukemia (CML).\n\nThe cells were thawed and acclimatized for 48 hours in StemMACS HSC Expansion Media XF (Miltenyi Biotec) supplemented with StemMACS HSC Expansion Cocktail (Miltenyi Biotec) at 37°C in a humidified atmosphere containing 5% CO2.\n\n4 samples of 2000000 HSPCs in 2 ml media each were then prepared and treated for 24 hours:\ncarboplatin-high: 150 µg/ml carboplatin\ncarboplatin-low: 18.75 µg/ml carboplatin\ngemcitabine: 25 ng/ml gemcitabine\ncontrol: no drug\n\nSingle-cells were subsequently extracted using the ddSEQ™ Single-Cell Isolator (Bio-Rad) and later sequenced using the SureCell™ Whole Transcriptome Analysis 3' Library Prep Kit (Illumina) on the NextSeq 500 System (Illumina) using the NextSeq 500/550 High Output Kit v2.5 150 Cycles (Illumina) all following the manufacturer's instructions.\n\nFASTQ-files were then processed following the ddSeeker (Romagnoli, D., et al., BMC Genomics 2018, doi:10.1186/s12864-018-5249-x) and Drop-seq (Macosko, E.Z., et al., Cell 2015, doi:10.1016/j.cell.2015.05.002) protocols for processing scRNA-seq data to yield the final digital gene expression for each cell.","abstract":"The study used cryopreserved hematopoietic stem and progenitor cells (HSPCs) harvested from one patient with chronic myelogenous leukemia (CML).\n\nThe cells were thawed and acclimatized for 48 hours in StemMACS HSC Expansion Media XF (Miltenyi Biotec) supplemented with StemMACS HSC Expansion Cocktail (Miltenyi Biotec) at 37°C in a humidified atmosphere containing 5% CO2.\n\n4 samples of 2000000 HSPCs in 2 ml media each were then prepared and treated for 24 hours:\ncarboplatin-high: 150 µg/ml carboplatin\ncarboplatin-low: 18.75 µg/ml carboplatin\ngemcitabine: 25 ng/ml gemcitabine\ncontrol: no drug\n\nSingle-cells were subsequently extracted using the ddSEQ™ Single-Cell Isolator (Bio-Rad) and later sequenced using the SureCell™ Whole Transcriptome Analysis 3' Library Prep Kit (Illumina) on the NextSeq 500 System (Illumina) using the NextSeq 500/550 High Output Kit v2.5 150 Cycles (Illumina) all following the manufacturer's instructions.\n\nFASTQ-files were then processed following the ddSeeker (Romagnoli, D., et al., BMC Genomics 2018, doi:10.1186/s12864-018-5249-x) and Drop-seq (Macosko, E.Z., et al., Cell 2015, doi:10.1016/j.cell.2015.05.002) protocols for processing scRNA-seq data to yield the final digital gene expression for each cell.","study_type":"Other","pubmed_ids":[32422951],"external_links":null,"is_released":true,"released_date":"2020-04-27T09:44:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004382","title":"Transcriptome Milan","description":null,"abstract":"The aim of this study is to compare DCIS and IBC in a subtype stratified manner in several genomic levels.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004383","title":"Matching of actionable mutations with therapies in cancer patients: comparison of three commercial decision support platforms","description":"Purpose: In oncology, precision medicine centers on tailoring the most appropriate therapy to a patient according to their tumor molecular profile. We addressed the question whether there is a consensus in the classification of actionability of somatic variants and their alignment to treatment recommendations. To this end, we evaluated three commercial clinical decision support tools to assess their variant classification and drug matching strategies.Methods: In this two centers study 48 patients with metastatic breast (n=12), colorectal (n=17) or non-small cell lung cancer (n=19) were recruited based on circulating tumor DNA levels in peripheral blood. In individual patients’ plasma samples, we established somatic copy number alterations and somatic mutations across a 77 cancer-associated gene panel and exposed the obtained molecular profiles to the decision support packages NAVIFY Mutation Profiler (NMP; Roche), Qiagen Clinical Insight (QCI) Interpret (Qiagen) and CureMatch Bionov (CureMatch).Results: In the plasma samples, altogether 492 somatic alterations were assessed. Each decision support platform varied in their format of data input, mode of variant classification and strategies for identifying druggable targets and clinical trials, which resulted in discrepancies in tier classification as well as designations of actionability. The frequency of concordant actionable events for tier I-A or tier I-B classifications, i.e. those with the strongest clinical evidence, was only 4.3%, 9.5% and 28.4% when comparing NMP with QCI, NMP with CureMatch, and CureMatch with QCI, respectively. As a consequence, the obtained treatment recommendations differed drastically, and alignment of treatment recommendations was limited to established predictive markers.Conclusions: The lack of standards for the extraction of treatment recommendations from comprehensive tumor molecular profiling data challenge the promising concepts of precision oncology.","abstract":"Purpose: In oncology, precision medicine centers on tailoring the most appropriate therapy to a patient according to their tumor molecular profile. We addressed the question whether there is a consensus in the classification of actionability of somatic variants and their alignment to treatment recommendations. To this end, we evaluated three commercial clinical decision support tools to assess their variant classification and drug matching strategies.Methods: In this two centers study 48 patients with metastatic breast (n=12), colorectal (n=17) or non-small cell lung cancer (n=19) were recruited based on circulating tumor DNA levels in peripheral blood. In individual patients’ plasma samples, we established somatic copy number alterations and somatic mutations across a 77 cancer-associated gene panel and exposed the obtained molecular profiles to the decision support packages NAVIFY Mutation Profiler (NMP; Roche), Qiagen Clinical Insight (QCI) Interpret (Qiagen) and CureMatch Bionov (CureMatch).Results: In the plasma samples, altogether 492 somatic alterations were assessed. Each decision support platform varied in their format of data input, mode of variant classification and strategies for identifying druggable targets and clinical trials, which resulted in discrepancies in tier classification as well as designations of actionability. The frequency of concordant actionable events for tier I-A or tier I-B classifications, i.e. those with the strongest clinical evidence, was only 4.3%, 9.5% and 28.4% when comparing NMP with QCI, NMP with CureMatch, and CureMatch with QCI, respectively. As a consequence, the obtained treatment recommendations differed drastically, and alignment of treatment recommendations was limited to established predictive markers.Conclusions: The lack of standards for the extraction of treatment recommendations from comprehensive tumor molecular profiling data challenge the promising concepts of precision oncology.","study_type":"Other","pubmed_ids":[32967919],"external_links":null,"is_released":true,"released_date":"2020-04-28T12:27:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004384","title":"Profiling of circulating tumor DNA for treatment selection in patients with advanced and refractory carcinoma: A prospective, two-stage phase II individualized cancer treatment trial","description":"PURPOSETo evaluate the success of a targeted therapy selected by molecular profiling (MP) of circulating tumor DNA in patients with advanced and refractory carcinoma in a prospective setting.PATIENTS AND METHODSIn this single-center trial, patients with advanced and refractory carcinoma were enrolled and a mandatory blood draw as well as an optional tissue biopsy were obtained for molecular profiling. Whole-genome sequencing and a cancer hotspot panel were performed on plasma DNA and tissue DNA (hotspot panel only) and publicly available databases were used to match the molecular profile to targeted treatments based on the annotated results, which were discussed at a molecular tumor board. The primary endpoint was the progression-free survival (PFS) ratio (PFS on MP-guided therapy / PFS on the last evidence-based therapy), whereas the success of the targeted therapy was defined as a PFS ratio ≥ 1.2. Secondary endpoints were the number of patients for whom an anti-tumor drug could be defined based on the molecular profile, the overall survival (OS) and the overall radiographic response rate (ORR).  In order to test the impact of molecular profile-treatment matching strategies, we retrospectively analyzed selected cases via the CureMatch PreciGENE™ decision support algorithm.RESULTSAfter inclusion of 24 patients, an interim analysis was performed. Overall, MP yielded informative results from 20 patients (83%), meaning that tumor-specific DNA content in plasma was above 5% and that either a somatic mutation or copy number alteration could be detected from plasma or tissue. A potential tumor-specific drug could be matched in 11 out of 24 patients (46%). Eight patients (33%) received a matched treatment. Median PFS in the matched treatment group was 61 days (IQR 49.8-71) compared to 78 days (IQR 61.5-144) of the last evidence-based treatment, resulting in a median PFS ratio of 0.7 (IQR 0.6-0.9). Hence, as no patient experienced a PFS ratio ≥ 1.2, the study was terminated. Whereas database-based molecular profiling matching suggested mainly single drugs, the retrospective CureMatch analysis identified either a 2-drug or 3-drug combination option in each of the tested cases, including a case for which no therapy was previously identified.CONCLUSIONOur study is the first to report prospective outcome results on the efficacy of plasma DNA profiling-based treatment, but it challenges the routine use of this procedure for treatment selection in advanced cancer patients outside of clinical trials. More innovative approaches to study design, matching algorithms and drug allocation strategies are necessary to achieve improved patient outcomes.","abstract":"PURPOSETo evaluate the success of a targeted therapy selected by molecular profiling (MP) of circulating tumor DNA in patients with advanced and refractory carcinoma in a prospective setting.PATIENTS AND METHODSIn this single-center trial, patients with advanced and refractory carcinoma were enrolled and a mandatory blood draw as well as an optional tissue biopsy were obtained for molecular profiling. Whole-genome sequencing and a cancer hotspot panel were performed on plasma DNA and tissue DNA (hotspot panel only) and publicly available databases were used to match the molecular profile to targeted treatments based on the annotated results, which were discussed at a molecular tumor board. The primary endpoint was the progression-free survival (PFS) ratio (PFS on MP-guided therapy / PFS on the last evidence-based therapy), whereas the success of the targeted therapy was defined as a PFS ratio ≥ 1.2. Secondary endpoints were the number of patients for whom an anti-tumor drug could be defined based on the molecular profile, the overall survival (OS) and the overall radiographic response rate (ORR).  In order to test the impact of molecular profile-treatment matching strategies, we retrospectively analyzed selected cases via the CureMatch PreciGENE™ decision support algorithm.RESULTSAfter inclusion of 24 patients, an interim analysis was performed. Overall, MP yielded informative results from 20 patients (83%), meaning that tumor-specific DNA content in plasma was above 5% and that either a somatic mutation or copy number alteration could be detected from plasma or tissue. A potential tumor-specific drug could be matched in 11 out of 24 patients (46%). Eight patients (33%) received a matched treatment. Median PFS in the matched treatment group was 61 days (IQR 49.8-71) compared to 78 days (IQR 61.5-144) of the last evidence-based treatment, resulting in a median PFS ratio of 0.7 (IQR 0.6-0.9). Hence, as no patient experienced a PFS ratio ≥ 1.2, the study was terminated. Whereas database-based molecular profiling matching suggested mainly single drugs, the retrospective CureMatch analysis identified either a 2-drug or 3-drug combination option in each of the tested cases, including a case for which no therapy was previously identified.CONCLUSIONOur study is the first to report prospective outcome results on the efficacy of plasma DNA profiling-based treatment, but it challenges the routine use of this procedure for treatment selection in advanced cancer patients outside of clinical trials. More innovative approaches to study design, matching algorithms and drug allocation strategies are necessary to achieve improved patient outcomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004385","title":"ISARIC-4C whole blood RNA-seq of COVID19 patients","description":null,"abstract":"RNA extracted and poly-A selected from whole blood collected from hospitalized COVID-19 patients at up to 4 time points over the course of their treatment (R1 = admission, S3 = serial day 3, S9 = serial day 9, C28 = convalescent day 28+).","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004386","title":"Bulk RNAseq gene expression of baseline tumors from metastatic urothelial bladder cancer patients (IMvigor210) and metastatic renal cell carcinoma (IMmotion150)","description":"We examined tumors from a large cohort of patients with metastatic urothelial bladder cancer (mUC) and metastatic renal cell carcinoma (mRCC) treated with an anti-PD-L1 agent (atezolizumab) and found that high tumor IL8 gene expression was associated with worse overall survival (OS). We further identified the tumoral immune presence based on Teff signature. We found that high tumor IL8 expression continued to be associated with worse OS even in inflamed tumors in mUC and mRCC.","abstract":"We examined tumors from a large cohort of patients with metastatic urothelial bladder cancer (mUC) and metastatic renal cell carcinoma (mRCC) treated with an anti-PD-L1 agent (atezolizumab) and found that high tumor IL8 gene expression was associated with worse overall survival (OS). We further identified the tumoral immune presence based on Teff signature. We found that high tumor IL8 expression continued to be associated with worse OS even in inflamed tumors in mUC and mRCC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-28T18:46:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004387","title":"Bulk RNAseq gene expression of baseline tumors from metastatic renal cell carcinoma patients (IMmotion150)","description":null,"abstract":"We examined tumors from a randomized trial of patients with metastatic renal cell carcinoma (mRCC) treated with either an anti-PD-L1 agent (atezolizumab),  atezolizumab+bevacizumab or sunitinib. We found that high tumor IL8 gene expression was associated with worse overall survival (OS) in mRCC patients treated with atezolizumab. In addition, we further identified the tumoral immune presence based on Teff signature. We found that high tumor IL8 expression continued to be associated with worse OS even in inflamed tumors in mRCC in patients treated with atezolizumab, but not with atezolizumab+bevacizumab or sunitinib.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004388","title":"Neuroblastoma and adrenal gland single-cell study","description":"Neuroblastoma is a pediatric tumor of the developing sympathetic nervous system. However, the cellular origin of neuroblastoma remains to be defined. Here, we study single-cell transcriptomes of neuroblastomas and normal human developing adrenal glands at various stages of embryonic and fetal development. We define normal differentiation trajectories during adrenal medullary development and identify the cellular origin of neuroblastoma. Importantly, adrenergic and mesenchymal neuroblastomas with varying clinical phenotypes match different temporal states along normal differentiation trajectories, with the degree of differentiation corresponding to clinical prognosis.","abstract":"Neuroblastoma is a pediatric tumor of the developing sympathetic nervous system. However, the cellular origin of neuroblastoma remains to be defined. Here, we study single-cell transcriptomes of neuroblastomas and normal human developing adrenal glands at various stages of embryonic and fetal development. We define normal differentiation trajectories during adrenal medullary development and identify the cellular origin of neuroblastoma. Importantly, adrenergic and mesenchymal neuroblastomas with varying clinical phenotypes match different temporal states along normal differentiation trajectories, with the degree of differentiation corresponding to clinical prognosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-29T21:35:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004389","title":"Population structure analysis guided Whole Genome Sequencing of representatives in the admixed population of the United Arab Emirates","description":null,"abstract":"Whole Genome Sequences (WGS) of four nationals of the United Arab Emirates at 27X coverage or more were completed and described. Representatives were chosen based on their central location within the subpopulation on a Principal Component Analysis (PCA) and the degree to which they were admixed. Novel genomic variation among the different subgroups of the UAE population are reported","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004390","title":"Subtype specific studies of breast cancer progression. Milan cohort.","description":"The aim of this study is to compare DCIS and IBC in a subtype stratified manner in several genomic levels (gene expression, copy number, methylation).The data in this archive is supplementary to previously published data.","abstract":"The aim of this study is to compare DCIS and IBC in a subtype stratified manner in several genomic levels (gene expression, copy number, methylation).The data in this archive is supplementary to previously published data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-30T10:18:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004391","title":"Paediatric_and_adult_nasal_RNAseq___COVID19","description":"Understanding infectivity, progression and disease severity of COVID-19 in children.\n\nUnderstanding infectivity, progression and disease severity of COVID-19 in children: It has been observed that COVID-19 infection appears to present with reduced clinical severity and prevalence within children (&lt;18 years) compared to adults. This project as part of a national collaborative initiative seeks to answer this question.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Understanding infectivity, progression and disease severity of COVID-19 in children.\n\nUnderstanding infectivity, progression and disease severity of COVID-19 in children: It has been observed that COVID-19 infection appears to present with reduced clinical severity and prevalence within children (&lt;18 years) compared to adults. This project as part of a national collaborative initiative seeks to answer this question.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-30T10:28:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004392","title":"Genomic study of an AT-AML","description":"Ataxia Telangiectasia (A-T) is caused by biallelic mutations in ATM and confers predisposition to cancer, with acute myeloid leukaemia (AML) being rarely observed. We investigated an AML arising in an A-T patient for secondary genetic events by performing whole exome sequencing of serial samples over the disease course. AML samples were compared to a reference \"germline\" sample from a much earlier time point. Goldgraben et al 2020, Pediatric Blood &amp; Cancer","abstract":"Ataxia Telangiectasia (A-T) is caused by biallelic mutations in ATM and confers predisposition to cancer, with acute myeloid leukaemia (AML) being rarely observed. We investigated an AML arising in an A-T patient for secondary genetic events by performing whole exome sequencing of serial samples over the disease course. AML samples were compared to a reference \"germline\" sample from a much earlier time point. Goldgraben et al 2020, Pediatric Blood &amp; Cancer","study_type":"Other","pubmed_ids":[32383811],"external_links":null,"is_released":true,"released_date":"2020-04-30T10:49:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004393","title":"Detailed molecular and immune marker profiling of archival prostate cancer samples","description":null,"abstract":"Prostate cancer is a significant global health issue, and limitations to current patient management pathways often result in overtreatment or undertreatment. New ways to stratify patients are urgently needed. We conducted a feasibility study of such novel assessments, looking for associations between genomic changes and lymphocyte infiltration. An innovative workflow using an in-house targeted sequencing panel, immune cell profiling using an image analysis pipeline, RNA sequencing, and exome sequencing in select cases was tested. Gene fusions were profiled by RNA sequencing in 27 of 27 cases, and a significantly higher tumor-infiltrating lymphocyte (TIL) count was noted in tumors without a TMPRSS2:ERG fusion compared with those with the fusion (P = 0.01). Although this finding was not replicated in a larger validation set (n = 436) of The Cancer Genome Atlas images, there was a trend in the same direction. Differential expression analysis of TIL-high and TIL-low tumors revealed the enrichment of both innate and adaptive immune response pathways. Mutations in mismatch repair genes (MLH1 and MSH6 mutations in 1 of 27 cases) were identified. We describe a potential immune escape mechanism in TMPRSS2:ERG fusion-positive tumors. Detailed profiling, as shown herein, can provide novel insights into tumor biology. Likely differences with findings with other cohorts are related to methods used to define region of interest, but this warrants further study in a larger cohort.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004394","title":"Genome sequencing of oesophagus atresia families","description":"To gain insight into gene variants and genes associated with isolated Oesophageal atresia (OA) we conducted whole genome sequencing on samples from three families with recurrent cases affected by congenital and isolated tracheoesophageal fistula (TEF).","abstract":"To gain insight into gene variants and genes associated with isolated Oesophageal atresia (OA) we conducted whole genome sequencing on samples from three families with recurrent cases affected by congenital and isolated tracheoesophageal fistula (TEF).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-30T12:23:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004395","title":"glioblastoma and glioblastoma stem cells (GSCs), RNA-seq and WGS","description":"Characterization of glioblastoma tumors and glioblastoma stem cells (GSCs) lines via RNA-seq and/or WGS profiling.","abstract":"Characterization of glioblastoma tumors and glioblastoma stem cells (GSCs) lines via RNA-seq and/or WGS profiling.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-30T14:56:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004396","title":"Detailed molecular and immune marker profiling of archival prostate cancer samples","description":null,"abstract":"Prostate cancer is a significant global health issue, and limitations to current patient management pathways often result in overtreatment or undertreatment. New ways to stratify patients are urgently needed. We conducted a feasibility study of such novel assessments, looking for associations between genomic changes and lymphocyte infiltration. An innovative workflow using an in-house targeted sequencing panel, immune cell profiling using an image analysis pipeline, RNA sequencing, and exome sequencing in select cases was tested. Gene fusions were profiled by RNA sequencing in 27 of 27 cases, and a significantly higher tumor-infiltrating lymphocyte (TIL) count was noted in tumors without a TMPRSS2:ERG fusion compared with those with the fusion (P = 0.01). Although this finding was not replicated in a larger validation set (n = 436) of The Cancer Genome Atlas images, there was a trend in the same direction. Differential expression analysis of TIL-high and TIL-low tumors revealed the enrichment of both innate and adaptive immune response pathways. Mutations in mismatch repair genes (MLH1 and MSH6 mutations in 1 of 27 cases) were identified. We describe a potential immune escape mechanism in TMPRSS2:ERG fusion-positive tumors. Detailed profiling, as shown herein, can provide novel insights into tumor biology. Likely differences with findings with other cohorts are related to methods used to define region of interest, but this warrants further study in a larger cohort.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-30T15:19:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004397","title":"GBM stem cell lines and PRMT5 inhibitor","description":null,"abstract":"RNA-seq data use in a study evaluating the effect of an PRMT5 inhibitor on GSC lines.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-04-30T17:37:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004398","title":"Resequencing (smMIPS) of candidate gene, ACAN, for Otosclerosis (2020)","description":null,"abstract":"Purpose: In this study we investigated the association of ACAN variants with otosclerosis, a frequent cause of hearing loss among young adults. \nMethods: We sequenced the coding, 5’-UTR and 3’-UTR regions of ACAN in 1497 unrelated otosclerosis cases and 1437 matched controls. The association between variants in ACAN and the disease risk was tested through single variant and gene-based association tests.\nResults: After correction for multiple testing, 14 variants were significantly associated with otosclerosis, ten of which represented independent association signals. Allelic odds ratios of the variants identified four predisposing and ten protective variants. Gene-based tests showed association of very rare variants in the 3’-UTR with the phenotype.\nConclusion: The associated variants are all located in the CS domain of ACAN and include both protective and predisposing variants with a broad spectrum of effect sizes and population frequencies. This includes variants with a strong effect size and low frequency, typical for monogenic diseases, to low effect size variants with high frequency, characteristic for common complex traits. This single-gene allelic spectrum with both protective and predisposing alleles is unique in the field of complex diseases. In conclusion, these findings are a significant advancement to the understanding of the etiology of otosclerosis.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004399","title":"Analysis of Burden of Somatic Alterations in 55 Diffuse Gliomas","description":null,"abstract":"Little is known on the molecular mechanisms shaping the glioma genome. In this work, we quantified various types of molecular alterations, the consequence different the oncogenic mechanisms in gliomas. This whole-exome sequencing based analysis revealed differences between molecular subsets of adult diffuse gliomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004400","title":"Analysis of Burden of Somatic Alterations in 55 Diffuse Gliomas","description":null,"abstract":"Little is known on the molecular mechanisms shaping the glioma genome. In this work, we quantified various types of molecular alterations, the consequence different the oncogenic mechanisms in gliomas. This whole-exome sequencing based analysis revealed differences between molecular subsets of adult diffuse gliomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004401","title":"H3Africa - Respiratory Microbiota of African Children","description":"Shotgun metagenomic sequencing of nasopharyngeal (NP) samples, from children enrolled in a PCV13-vaccinated South African birth cohort was used to explore strain-level pneumococcal colonization patterns and transmission dynamics, and associated antimicrobial-resistance determinants. NP swabs were collected at two-week intervals from birth through the first year of life from 137 infants. Pneumococcal isolates were serotyped and tested for phenotypic antimicrobial resistance. 196 NP samples from a subset of 23 infants were then selected based on changes in serotype or antimicrobial resistance. DNA was extracted directly from the enriched NP samples and shotgun metagenomic sequencing performed. Reads were assembled and aligned against reference pneumococcal genomes. in silico pneumococcal capsular, multilocus sequence typing, and resistome analyses were performed.","abstract":"Shotgun metagenomic sequencing of nasopharyngeal (NP) samples, from children enrolled in a PCV13-vaccinated South African birth cohort was used to explore strain-level pneumococcal colonization patterns and transmission dynamics, and associated antimicrobial-resistance determinants. NP swabs were collected at two-week intervals from birth through the first year of life from 137 infants. Pneumococcal isolates were serotyped and tested for phenotypic antimicrobial resistance. 196 NP samples from a subset of 23 infants were then selected based on changes in serotype or antimicrobial resistance. DNA was extracted directly from the enriched NP samples and shotgun metagenomic sequencing performed. Reads were assembled and aligned against reference pneumococcal genomes. in silico pneumococcal capsular, multilocus sequence typing, and resistome analyses were performed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-05T08:45:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004402","title":"Transcriptomic analysis of Acute Myeloid Leukemia stem cells","description":"Acute Myeloid Leukemia (AML) is characterized by the accumulation of clonal myeloid blast cells unable to differentiate into mature leukocytes. Chemotherapy induces remission in the majority of patients, but relapse rates are high and lead to poor clinical outcomes. Since this is primarily caused by chemotherapy-resistant leukemic stem cells (LSCs), it is essential to eradicate LSCs to improve patient survival. LSCs have predominantly been studied at the transcript level, thus lacking information about post-transcriptionally regulated genes and associated networks. Here we extend our previous report on LSC proteomes to healthy age-matched hematopoietic stem and progenitor cells (HSPCs) and correlate the proteomes to the corresponding transcriptomes. By comparing LSCs to leukemic blasts and healthy HSPCs, we validate candidate LSC markers and highlight novel and potentially targetable proteins that are absent or only lowly expressed in HSPCs. In addition, our data provides strong evidence that LSCs harbor a characteristic energy metabolism, adhesion molecule composition, as well as RNA processing properties. Furthermore, correlating proteome and transcript data of the same individual samples highlights the strength of proteome analyses, which are particularly potent in detecting alterations in metabolic pathways. In summary, our study provides a comprehensive proteomic and transcriptomic characterization of functionally validated LSCs, blasts and healthy HSPCs, representing a valuable resource helping to design LSC-directed therapies.","abstract":"Acute Myeloid Leukemia (AML) is characterized by the accumulation of clonal myeloid blast cells unable to differentiate into mature leukocytes. Chemotherapy induces remission in the majority of patients, but relapse rates are high and lead to poor clinical outcomes. Since this is primarily caused by chemotherapy-resistant leukemic stem cells (LSCs), it is essential to eradicate LSCs to improve patient survival. LSCs have predominantly been studied at the transcript level, thus lacking information about post-transcriptionally regulated genes and associated networks. Here we extend our previous report on LSC proteomes to healthy age-matched hematopoietic stem and progenitor cells (HSPCs) and correlate the proteomes to the corresponding transcriptomes. By comparing LSCs to leukemic blasts and healthy HSPCs, we validate candidate LSC markers and highlight novel and potentially targetable proteins that are absent or only lowly expressed in HSPCs. In addition, our data provides strong evidence that LSCs harbor a characteristic energy metabolism, adhesion molecule composition, as well as RNA processing properties. Furthermore, correlating proteome and transcript data of the same individual samples highlights the strength of proteome analyses, which are particularly potent in detecting alterations in metabolic pathways. In summary, our study provides a comprehensive proteomic and transcriptomic characterization of functionally validated LSCs, blasts and healthy HSPCs, representing a valuable resource helping to design LSC-directed therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-05T13:27:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004403","title":"Patterns of chromosome 18 loss of heterozygosity in multifocal ileal neuroendocrine tumors","description":null,"abstract":"Ileal neuroendocrine tumors (NETs) represent the most common neoplasm of the small intestine. Although up to 50% of patients with ileal NETs are diagnosed with multifocal disease, the mechanisms by which multifocal ileal NETs arise are not yet understood. In this study, we analyzed genome-wide sequencing data to examine patterns of copy number variation in 40 synchronous primary ileal NETs derived from three patients. Chromosome (chr) 18 loss of heterozygosity (LOH) was the most frequent copy number alteration identified; however, not all primary tumors from the same patient had evidence of this LOH. Our data revealed three distinct patterns of chr18 allelic loss, indicating that primary tumors from the same patient can present different LOH patterns including retention of either parental allele. In conclusion, our results are consistent with the model that multifocal ileal NETs originate independently. In addition, they suggest that there is no specific germline allele on chr18 that is the target of somatic LOH.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004404","title":"Accelerated single cell seeding in relapsed multiple myeloma","description":null,"abstract":"The malignant progression of multiple myeloma is characterized by the seeding of cancer cells in different anatomic sites followed by their clonal expansion. It has been demonstrated that this spatial evolution at varying anatomic sites is characterized by genomic heterogeneity. However, it is unclear whether each anatomic site at relapse reflects the expansion of pre-existing but previously undetected disease or secondary seeding from other sites. Furthermore, genomic evolution over time at spatially distinct sites of disease has not been investigated in a systematic manner.\n\nTo address this, we interrogated 25 samples, by whole genome sequencing, collected at autopsy from 4 patients with relapsed multiple myeloma and demonstrated that each site had a unique evolutionary trajectory characterized by distinct single and complex structural variants and copy number changes. By analyzing the landscape of mutational signatures at these sites and for an additional set of 125 published whole exomes collected from 51 patients, we demonstrate the profound mutagenic effect of melphalan and platinum in relapsed multiple myeloma. Chemotherapy-related mutagenic processes are known to introduce hundreds of unique mutations in each surviving cancer cell. These mutations can be detectable by bulk sequencing only in cases of clonal expansion of a single cancer cell bearing the mutational signature linked to chemotherapy exposure thus representing a unique single-cell genomic barcode linked to a discrete time window in each patient’s life. We leveraged this concept to show that multiple myeloma systemic seeding is accelerated at clinical relapse and appears to be driven by the survival and subsequent expansion of a single myeloma cell following treatment with high dose melphalan therapy and autologous stem cell transplant.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-05T20:21:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004405","title":"Homologous recombination DNA repair deficiency and PARP inhibition activity in primary triple negative breast cancer","description":"Triple negative breast cancer (TNBC) encompasses molecularly different subgroups, with a subgroup harboring evidence of defective homologous recombination (HR) DNA repair. Within a phase 2 window clinical trial, RIO trial (EudraCT 2014-003319-12), we investigate the activity of PARP inhibitors in 43 patients with untreated TNBC. The primary endpoint, decreased Ki67, occurs in 12% of TNBC. Multiple different approaches identify HR deficiency in the majority of TNBC, 69% with the mutational-signature-based HRDetect assay. Cancers with mutational signatures of HR deficiency have a functional defect in HR. Following rucaparib treatment there is no association of Ki67 change with HR deficiency. In contrast, early circulating tumor DNA dynamics identify activity of rucaparib in cancers with mutation-signatures of HR deficiency, with rucaparib inducing expression of interferon response genes in HR deficient cancers. The majority of TNBCs have a defect in DNA repair, identifiable by mutational signature analysis, that may be targetable with PARP inhibitors.","abstract":"Triple negative breast cancer (TNBC) encompasses molecularly different subgroups, with a subgroup harboring evidence of defective homologous recombination (HR) DNA repair. Within a phase 2 window clinical trial, RIO trial (EudraCT 2014-003319-12), we investigate the activity of PARP inhibitors in 43 patients with untreated TNBC. The primary endpoint, decreased Ki67, occurs in 12% of TNBC. Multiple different approaches identify HR deficiency in the majority of TNBC, 69% with the mutational-signature-based HRDetect assay. Cancers with mutational signatures of HR deficiency have a functional defect in HR. Following rucaparib treatment there is no association of Ki67 change with HR deficiency. In contrast, early circulating tumor DNA dynamics identify activity of rucaparib in cancers with mutation-signatures of HR deficiency, with rucaparib inducing expression of interferon response genes in HR deficient cancers. The majority of TNBCs have a defect in DNA repair, identifiable by mutational signature analysis, that may be targetable with PARP inhibitors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-06T11:31:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004406","title":"Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring","description":"In many areas of oncology, we lack sensitive tools to track low burden disease. While cell-free DNA (cfDNA) shows promise in detecting cancer mutations, we found that the combination of low tumor fraction (TF) and limited number of DNA fragments restricts low disease burden monitoring through the prevailing deep targeted sequencing paradigm. We reasoned that breadth may supplant depth of sequencing to overcome the barrier of cfDNA abundance. Whole genome sequencing (WGS) of cfDNA allowed ultra-sensitive detection, capitalizing on the cumulative signal of thousands of somatic mutations observed in solid malignancies, with TF detection sensitivity as low as 10-5. The WGS approach enabled dynamic tumor burden tracking and post-operative residual disease detection, associated with adverse outcome. Thus, we present an orthogonal framework for cfDNA cancer monitoring via genome wide mutational integration, enabling ultra-sensitive detection, overcoming the limitation of cfDNA abundance, and empowering treatment optimization in low-disease burden oncology care","abstract":"In many areas of oncology, we lack sensitive tools to track low burden disease. While cell-free DNA (cfDNA) shows promise in detecting cancer mutations, we found that the combination of low tumor fraction (TF) and limited number of DNA fragments restricts low disease burden monitoring through the prevailing deep targeted sequencing paradigm. We reasoned that breadth may supplant depth of sequencing to overcome the barrier of cfDNA abundance. Whole genome sequencing (WGS) of cfDNA allowed ultra-sensitive detection, capitalizing on the cumulative signal of thousands of somatic mutations observed in solid malignancies, with TF detection sensitivity as low as 10-5. The WGS approach enabled dynamic tumor burden tracking and post-operative residual disease detection, associated with adverse outcome. Thus, we present an orthogonal framework for cfDNA cancer monitoring via genome wide mutational integration, enabling ultra-sensitive detection, overcoming the limitation of cfDNA abundance, and empowering treatment optimization in low-disease burden oncology care","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-06T13:16:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004407","title":"Chemotherapy induces canalization of cell state in childhood B-cell precursor acute lymphoblastic leukemia","description":"Comparison of intratumor genetic heterogeneity in cancer at diagnosis and relapse suggests that chemotherapy induces bottleneck selection of subclonal genotypes. However, evolutionary events subsequent to chemotherapy could also explain changes in clonal dominance seen at relapse. We therefore investigated the mechanisms of selection in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) during induction chemotherapy where maximal cytoreduction occurs. To distinguish stochastic versus deterministic events, individual leukemias were transplanted into multiple xenografts and chemotherapy administered. Analyses of the immediate post-treatment leukemic residuum at single-cell resolution revealed that chemotherapy has little impact on genetic heterogeneity. Rather, it acts on extensive, previously unappreciated, transcriptional and epigenetic heterogeneity in BCP-ALL, dramatically reducing the spectrum of cell states represented, leaving a genetically polyclonal but phenotypically uniform population, with hallmark signatures relating to developmental stage, cell cycle and metabolism. Hence, canalization of the cell state accounts for a significant component of bottleneck selection during induction chemotherapy.","abstract":"Comparison of intratumor genetic heterogeneity in cancer at diagnosis and relapse suggests that chemotherapy induces bottleneck selection of subclonal genotypes. However, evolutionary events subsequent to chemotherapy could also explain changes in clonal dominance seen at relapse. We therefore investigated the mechanisms of selection in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) during induction chemotherapy where maximal cytoreduction occurs. To distinguish stochastic versus deterministic events, individual leukemias were transplanted into multiple xenografts and chemotherapy administered. Analyses of the immediate post-treatment leukemic residuum at single-cell resolution revealed that chemotherapy has little impact on genetic heterogeneity. Rather, it acts on extensive, previously unappreciated, transcriptional and epigenetic heterogeneity in BCP-ALL, dramatically reducing the spectrum of cell states represented, leaving a genetically polyclonal but phenotypically uniform population, with hallmark signatures relating to developmental stage, cell cycle and metabolism. Hence, canalization of the cell state accounts for a significant component of bottleneck selection during induction chemotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-07T17:38:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004408","title":"Search for genetic variants influencing gestational weight gain in type 1 diabetes patients by genome wide association method","description":"Clinical data suggest that BMI and gestational weight gain (GWG) are strongly interconnected phenotypes, however the genetic basis of the latter is rather unclear. Here we aim to investigate the genetic factors associated with GWG from the perspective of the genetics of obesity.","abstract":"Clinical data suggest that BMI and gestational weight gain (GWG) are strongly interconnected phenotypes, however the genetic basis of the latter is rather unclear. Here we aim to investigate the genetic factors associated with GWG from the perspective of the genetics of obesity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-08T08:05:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004409","title":"Plasma DNA profile in DNASE1L3 deficiency-Mouse AAV samples","description":"Plasma DNA profile in DNASE1L3 deficiency-Mouse AAV","abstract":"Plasma DNA profile in DNASE1L3 deficiency-Mouse AAV","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-08T09:45:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004410","title":"Scottish High Grade Serous Ovarian Cancer","description":"Scottish HGSOC samples were collected via local Bioresource facilities at Edinburgh, Glasgow, Dundee and Aberdeen and stored in liquid Nitrogen until required. HGSOC patients were determined from pathology records and were included in the study where there was matched tumour and whole blood samples. On receipt of tumour material the tumour was processed as follows: firstly, the tumour sample was divided into two for DNA and RNA extraction. Slivers of tissue were cut from the front and rear faces of the DNA sample, then fixed in formalin and embedded in paraffin wax. Sections from the front and rear tissues from all samples were examined by H&amp;E staining supplemented by WT1/p53 immunohistochemistry if required. Following pathology review, samples were only included if they met the following criteria: they were confirmed as HGSOC and there was greater than 40% tumour cellularity throughout the tumour, determined using the H&amp;E sections. Somatic DNA was extracted using the Qiagen DNeasy Blood and tissue kit (cat no 69504). The tissue was initially homogenised using a Qiagen Bioruptor, followed by the manufacturers recommended protocol (including RNase digestion step). Germline DNA was extracted from 1-3ml whole blood using the Qiagen FlexiGene kit (cat no 51206) following the manufacturers recommended protocol. The resulting DNA underwent quality control as follows: firstly, A260 and A280nm were measured on a Denovix DS-11 Fx to qualitatively illustrate A260/280nm and A260/230nm ratios as surrogate measures of DNA purity. A260/280 had to be 1.8 or greater and A260/230 had to be 2.0 or greater. Then, DNA was quantified using LifeTechnologies Qubit dsDNA BR kit (cat no Q32850) and we required a minimum of 50ul at 25ng/ul for WGS. Thirdly, DNA was diluted to 25ng/ul and a representative sample was loaded onto a 0.8% TAE gel, ran at 100v for 60mins and then imaged using a BioRad ChemiDoc imaging system to visualise the DNA quality. Only when all 4 quality control requirements were satisfied was the DNA sequenced. The DNA was sequenced at the Glasgow Precision Oncology Laboratories.","abstract":"Scottish HGSOC samples were collected via local Bioresource facilities at Edinburgh, Glasgow, Dundee and Aberdeen and stored in liquid Nitrogen until required. HGSOC patients were determined from pathology records and were included in the study where there was matched tumour and whole blood samples. On receipt of tumour material the tumour was processed as follows: firstly, the tumour sample was divided into two for DNA and RNA extraction. Slivers of tissue were cut from the front and rear faces of the DNA sample, then fixed in formalin and embedded in paraffin wax. Sections from the front and rear tissues from all samples were examined by H&amp;E staining supplemented by WT1/p53 immunohistochemistry if required. Following pathology review, samples were only included if they met the following criteria: they were confirmed as HGSOC and there was greater than 40% tumour cellularity throughout the tumour, determined using the H&amp;E sections. Somatic DNA was extracted using the Qiagen DNeasy Blood and tissue kit (cat no 69504). The tissue was initially homogenised using a Qiagen Bioruptor, followed by the manufacturers recommended protocol (including RNase digestion step). Germline DNA was extracted from 1-3ml whole blood using the Qiagen FlexiGene kit (cat no 51206) following the manufacturers recommended protocol. The resulting DNA underwent quality control as follows: firstly, A260 and A280nm were measured on a Denovix DS-11 Fx to qualitatively illustrate A260/280nm and A260/230nm ratios as surrogate measures of DNA purity. A260/280 had to be 1.8 or greater and A260/230 had to be 2.0 or greater. Then, DNA was quantified using LifeTechnologies Qubit dsDNA BR kit (cat no Q32850) and we required a minimum of 50ul at 25ng/ul for WGS. Thirdly, DNA was diluted to 25ng/ul and a representative sample was loaded onto a 0.8% TAE gel, ran at 100v for 60mins and then imaged using a BioRad ChemiDoc imaging system to visualise the DNA quality. Only when all 4 quality control requirements were satisfied was the DNA sequenced. The DNA was sequenced at the Glasgow Precision Oncology Laboratories.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-08T16:49:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004411","title":"Broad applications of a comprehensive patient-derived xenograft platform capturing the heterogeneity of renal cell carcinoma","description":null,"abstract":"Renal cell carcinoma (RCC) encompasses a heterogenous group of diseases, creating challenges in developing effective therapies. Pre-clinical models which are both translatable and capture the breadth of RCC are needed. Patient derived xenograft (PDX) models of RCC have been repeatedly shown to recapitulate the biological properties of the parent tumor and have been utilized to make major contributions to the field. Herein, we report the development of a comprehensive PDX platform which captures the histologic, genomic, and transcriptomic diversity of RCC. Additionally, we demonstrate broad applications of this platform including metabolomic profiling of tumors, the development of tissue and imaging-based biomarkers, as well as drug testing in selected molecular backgrounds. We have made all PDX lines (n=179) broadly available along with extensive histologic and molecular annotation, providing a valuable resource to the scientific community.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004412","title":"Potent neutralizing antibodies against SARS-CoV-2","description":"The COVID-19 pandemic urgently needs therapeutic and prophylactic interventions. Here we report the rapid identification of SARS-CoV-2 neutralizing antibodies by high-throughput single-cell RNA and VDJ sequencing of antigen-enriched B cells from 60 convalescent patients.","abstract":"The COVID-19 pandemic urgently needs therapeutic and prophylactic interventions. Here we report the rapid identification of SARS-CoV-2 neutralizing antibodies by high-throughput single-cell RNA and VDJ sequencing of antigen-enriched B cells from 60 convalescent patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-09T05:23:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004413","title":"Personalised Mapping of Tumour Development in Synchronous Colorectal Cancer Patients","description":"We performed an in-depth characterisation of 12 tumours from  3 syCRC patients by analysing histopathological, whole genome sequencing  and RNA-sequencing data. We assessed the extent of genetic overlap between synchronous tumours and examined associations between clinicopathological information and the molecular, microbial and immune features of each tumour genome.","abstract":"We performed an in-depth characterisation of 12 tumours from  3 syCRC patients by analysing histopathological, whole genome sequencing  and RNA-sequencing data. We assessed the extent of genetic overlap between synchronous tumours and examined associations between clinicopathological information and the molecular, microbial and immune features of each tumour genome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-11T11:19:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004414","title":"genome","description":null,"abstract":"test genome","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004415","title":"WES","description":"Whole exome sequencing of UTUC","abstract":"Whole exome sequencing of UTUC","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-11T15:09:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004416","title":"expression","description":"Expression study","abstract":"Expression study","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-11T15:15:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004417","title":"Methylation","description":"Methylation in UTUC","abstract":"Methylation in UTUC","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004418","title":"STM4 - Mouliere et al, 2018. Enhanced detection of circulating tumor DNA by fragment size analysis","description":null,"abstract":"Enhanced detection of circulating tumor DNA by fragment size analysis.\nMouliere et al, 2018\nThis submission contains all non-ovarian and non-normal/healthy data (see paired submission for these)","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-11T16:20:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004419","title":"SARS‐CoV‐2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells","description":"The SARS‐CoV‐2 pandemic affecting the human respiratory system severely challenges public health and urgently demands for increasing our understanding of COVID‐19 pathogenesis, especially host factors facilitating virus infection and replication. SARS‐CoV‐2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. While TMPRSS2 is strongly expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type. Interestingly, these transiently differentiating cells show an enrichment for pathways related to RHO GTPase function and viral processes suggesting increased vulnerability for SARS‐CoV‐2 infection. Our data provide a rich resource for future investigations of COVID‐19 infection and pathogenesis.","abstract":"The SARS‐CoV‐2 pandemic affecting the human respiratory system severely challenges public health and urgently demands for increasing our understanding of COVID‐19 pathogenesis, especially host factors facilitating virus infection and replication. SARS‐CoV‐2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. While TMPRSS2 is strongly expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type. Interestingly, these transiently differentiating cells show an enrichment for pathways related to RHO GTPase function and viral processes suggesting increased vulnerability for SARS‐CoV‐2 infection. Our data provide a rich resource for future investigations of COVID‐19 infection and pathogenesis.","study_type":"Other","pubmed_ids":[32246845],"external_links":null,"is_released":true,"released_date":"2020-05-12T09:21:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004420","title":"Genome-wide associations of human gut microbiota variation and implications for causal inference analyses","description":"Here we use appropriate taxon-specific models along with support from independent cohorts to show association between human host genotype and gut microbiome variation. Using fecal derived 16S rRNA gene sequences and host genotype data from the Flemish Gut Flora Project (FGFP) we identify genetic associations involving multiple microbial traits. Mendelian randomization analysis was able to estimate associations between microbial traits and disease, however in the absence of clear microbiome driven effects, caution is needed in interpretation. This work marks a growing catalog of genetic associations which will provide insight into the contribution of host genotype to gut microbiome. Despite this, the uncertain origin of association signals will likely complicate future work looking to dissect function or use associations for causal inference analysis.","abstract":"Here we use appropriate taxon-specific models along with support from independent cohorts to show association between human host genotype and gut microbiome variation. Using fecal derived 16S rRNA gene sequences and host genotype data from the Flemish Gut Flora Project (FGFP) we identify genetic associations involving multiple microbial traits. Mendelian randomization analysis was able to estimate associations between microbial traits and disease, however in the absence of clear microbiome driven effects, caution is needed in interpretation. This work marks a growing catalog of genetic associations which will provide insight into the contribution of host genotype to gut microbiome. Despite this, the uncertain origin of association signals will likely complicate future work looking to dissect function or use associations for causal inference analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-12T11:58:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004421","title":"Single-cell DNA amplicon sequencing reveals clonal heterogeneity and evolution in T-cell acute lymphoblastic leukemia","description":"T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive leukemia that is most frequent in children and is characterized by the presence of few chromosomal rearrangements and 10 to 20 somatic mutations in protein-coding regions at diagnosis. The majority of T-ALL cases harbor activating mutations in NOTCH1 together with mutations in genes implicated in kinase signaling, transcriptional regulation or protein translation. To obtain more insight in the level of clonal heterogeneity at diagnosis and during treatment, we used single-cell targeted DNA sequencing with the Tapestri platform. We designed a custom ALL panel and obtained accurate single-nucleotide variant and small insertion-deletion mutation calling for 305 amplicons covering 110 genes in about 4400 cells per sample and time point. A total of 108,188 cells were analyzed for 25 samples of 8 T-ALL patients. We typically observed a major clone at diagnosis (&gt;35% of the cells) accompanied by several minor clones of which some were less than 1% of the total number of cells. Four patients had &gt;2 NOTCH1 mutations some of which present in minor clones, indicating a strong pressure to acquire NOTCH1 mutations in developing T-ALL cells. By analyzing longitudinal samples, we detected the presence and clonal nature of residual leukemic cells as well as clones with a minor presence at diagnosis that evolved to clinically relevant major clones at later disease stages. Single-cell DNA amplicon sequencing is a sensitive assay to detect clonal architecture and evolution in T-ALL.","abstract":"T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive leukemia that is most frequent in children and is characterized by the presence of few chromosomal rearrangements and 10 to 20 somatic mutations in protein-coding regions at diagnosis. The majority of T-ALL cases harbor activating mutations in NOTCH1 together with mutations in genes implicated in kinase signaling, transcriptional regulation or protein translation. To obtain more insight in the level of clonal heterogeneity at diagnosis and during treatment, we used single-cell targeted DNA sequencing with the Tapestri platform. We designed a custom ALL panel and obtained accurate single-nucleotide variant and small insertion-deletion mutation calling for 305 amplicons covering 110 genes in about 4400 cells per sample and time point. A total of 108,188 cells were analyzed for 25 samples of 8 T-ALL patients. We typically observed a major clone at diagnosis (&gt;35% of the cells) accompanied by several minor clones of which some were less than 1% of the total number of cells. Four patients had &gt;2 NOTCH1 mutations some of which present in minor clones, indicating a strong pressure to acquire NOTCH1 mutations in developing T-ALL cells. By analyzing longitudinal samples, we detected the presence and clonal nature of residual leukemic cells as well as clones with a minor presence at diagnosis that evolved to clinically relevant major clones at later disease stages. Single-cell DNA amplicon sequencing is a sensitive assay to detect clonal architecture and evolution in T-ALL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004422","title":"Single-cell RNA-sequencing reveals that glioblastoma recapitulates a normal neurodevetlopmental hierarchy","description":"We discovered a conserved neural tri- lineage cancer hierarchy centered around glial progenitor-like cells. We also found that this progenitor population contains the majority of the cancer’s cycling cells, and, using RNA velocity, is often the originator of the other cell types. Finally, we show that this hierarchal map can be used to identify therapeutic targets specific to progenitor cancer stem cells. Our analyses show that normal brain development reconciles glioblastoma development, suggests a possible origin for glioblastoma hierarchy, and helps to identify cancer stem cell-specific targets.","abstract":"We discovered a conserved neural tri- lineage cancer hierarchy centered around glial progenitor-like cells. We also found that this progenitor population contains the majority of the cancer’s cycling cells, and, using RNA velocity, is often the originator of the other cell types. Finally, we show that this hierarchal map can be used to identify therapeutic targets specific to progenitor cancer stem cells. Our analyses show that normal brain development reconciles glioblastoma development, suggests a possible origin for glioblastoma hierarchy, and helps to identify cancer stem cell-specific targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-13T02:26:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004423","title":"Single cell RNAseq of Pmel-1 T cells studying the transcriptional landscape of CD226-hi cells","description":"Single cell RNAseq and CD226-CITEseq analyses of melanoma-specific Pmel-1 T cells. T cells were isolated from HCmel12hgp100 melanoma to study the transcriptional profile of T cell subsets defined based on their CD226 surface expression.","abstract":"Single cell RNAseq and CD226-CITEseq analyses of melanoma-specific Pmel-1 T cells. T cells were isolated from HCmel12hgp100 melanoma to study the transcriptional profile of T cell subsets defined based on their CD226 surface expression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004424","title":"RA-Map, A multi-omic survey of whole blood and subsets in early rheumatoid arthritis and vaccine study controls","description":"Rheumatoid arthritis (RA) is a chronic inflammatory disorder of unknown aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the molecular heterogeneity and pathogenesis of RA, we performed a comprehensive clinical and molecular profile of 267 RA patients for up to 18 months to establish a high quality biobank of barcoded samples that included plasma, serum, peripheral blood cells, whole blood RNA, RNA from lymphocyte and monocyte subsets, genomic DNA and urine. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and auto-antibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource for the development and application of targeted therapies for RA and reveal further insights into disease pathogenesis and therapeutic response.","abstract":"Rheumatoid arthritis (RA) is a chronic inflammatory disorder of unknown aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the molecular heterogeneity and pathogenesis of RA, we performed a comprehensive clinical and molecular profile of 267 RA patients for up to 18 months to establish a high quality biobank of barcoded samples that included plasma, serum, peripheral blood cells, whole blood RNA, RNA from lymphocyte and monocyte subsets, genomic DNA and urine. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and auto-antibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource for the development and application of targeted therapies for RA and reveal further insights into disease pathogenesis and therapeutic response.","study_type":"Other","pubmed_ids":[30487994],"external_links":null,"is_released":true,"released_date":"2020-05-13T13:33:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004425","title":"Parkinson's disease Human RNA-Seq data","description":null,"abstract":"This data was produced so that RNA-Seq","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004426","title":"MLKL variants in CRMO","description":null,"abstract":"ABSTRACT\nWe have isolated a mouse strain with a single missense mutation in the gene encoding MLKL, the essential effector of necroptotic cell death. The resulting D139V substitution lies within the two-helix ‘brace’ that connects the killer four-helix bundle and regulatory pseudokinase domains, and confers constitutive, RIPK3 independent, killing activity to MLKL. Homozygous mutant mice develop lethal postnatal inflammation of the salivary glands and mediastinum. The normal development of MlklD139V homozygotes until birth, and the absence of any overt phenotype in heterozygotes provides important in vivo precedent for the capacity of cells to clear activated MLKL. These observations offer an important insight into the potential disease-modulating roles of three common human MLKL polymorphisms that encode amino acid substitutions within or adjacent to the brace region. Compound heterozygosity of these variants is found at up to 12-fold the expected frequency in patients that suffer from a pediatric autoinflammatory disease, CRMO.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004427","title":"InsPIRE beta-cells","description":null,"abstract":"We explored the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human FAC sorted beta-cells from 26 donors.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004428","title":"Performance assessment of Total RNA sequencing of human biofluids and extracellular vesicles","description":null,"abstract":"RNA profiling has emerged as a powerful tool to investigate the biomarker potential of human biofluids. However, despite enormous interest in extracellular nucleic acids, RNA sequencing methods to quantify the total RNA content outside cells are rare. Here, we evaluate the performance of the SMARTer Stranded Total RNA-Seq method in human platelet-rich plasma, platelet-free plasma, urine, conditioned medium, and extracellular vesicles (EVs) from these biofluids. We found the method to be accurate, precise, compatible with low-input volumes and able to quantify a few thousand genes. We picked up distinct classes of RNA molecules, including mRNA, lncRNA, circRNA, miscRNA and pseudogenes. Notably, the read distribution and gene content drastically differ among biofluids. In conclusion, we are the first to show that the SMARTer method can be used for unbiased unraveling of the complete transcriptome of a wide range of biofluids and their extracellular vesicles.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-14T11:34:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004429","title":"The genomic landscape of primary cutaneous anaplastic large cell lymphoma (pcALCL)","description":"Primary cutaneous anaplastic large cell lymphoma (pcALCL) is the second most common variant of cutaneous T-cell lymphoma. We subjected tumor biopsies from patients with pcALCL to whole-genome sequencing, whole-exome sequencing and RNA-sequencing to investigate genomic alterations and deregulated gene expression in the disease.","abstract":"Primary cutaneous anaplastic large cell lymphoma (pcALCL) is the second most common variant of cutaneous T-cell lymphoma. We subjected tumor biopsies from patients with pcALCL to whole-genome sequencing, whole-exome sequencing and RNA-sequencing to investigate genomic alterations and deregulated gene expression in the disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-15T13:34:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004430","title":"Impact of genetic variants in clinical outcome of a cohort of patients with oropharyngeal squamous cell carcinoma","description":null,"abstract":"Background: Tobacco- or human papillomavirus- driven oropharyngeal squamous cell carcinomas (OpSCC) represent distinct clinical, biological and epidemiological entities. Objective: The aim of this study was to identify genetic variants based on somatic alterations in OpSCC samples from a non-European population, and to test for association with clinical features. Material and Methods: The entire coding region of 15 OpSCC driver genes was sequenced by next-generation sequencing in 51 OpSCC FFPE samples.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-15T21:32:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004431","title":"Dual-mTOR inhibitor Rapalink-1 reduces prostate cancer patient-derived xenograft growth and alters tumor heterogeneity","description":"Bone metastasis is the leading cause of prostate cancer (PCa) mortality, frequently marking the progression to castration-resistant PCa. In this study, we compared the molecular pathways enriched in a set of bone metastasis from breast and prostate cancer from snap-frozen tissue. To further model PCa drug resistance mechanisms, we used two patient-derived xenografts (PDX) models of bone-metastatic PCa, BM18 and LAPC9.","abstract":"Bone metastasis is the leading cause of prostate cancer (PCa) mortality, frequently marking the progression to castration-resistant PCa. In this study, we compared the molecular pathways enriched in a set of bone metastasis from breast and prostate cancer from snap-frozen tissue. To further model PCa drug resistance mechanisms, we used two patient-derived xenografts (PDX) models of bone-metastatic PCa, BM18 and LAPC9.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-16T14:54:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004432","title":"Single Cell Dissection of Nasopharyngeal Carcinoma","description":null,"abstract":"Nasopharyngeal carcinoma (NPC),  a heterogeneous epithelial tumor with heavy lymphocyte infiltration, is the most common head and neck cancer in southeast Asia. Efforts to identify prognostic markers and potential therapeutic targets have been hampered by the poor understanding of its cellular heterogeneity. Here, we applied single-cell RNA sequencing to comprehensively evaluate the multicellular ecosystem of 15 primary NPC tumors; the normal nasopharyngeal epithelial tissue from one patient with chronic nasopharyngitis was also collected. We also acquired bulk WES and RNA-seq data for 12 tumors. In this study, we retrospectively collected 128 non-metastatic, pretreatment, formalin-fixed, paraffin-embedded (FFPE) NPC were retrospectively collected. Total RNA was extracted and hybridised to an Affymetrix HTA 2.0 microarray.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004433","title":"Surgery in combination with immune checkpoint therapy as effective treatment for patients with metastatic cancer","description":null,"abstract":"Patients with stage 4 cancer generally have a dismal prognosis and eventually die from metastasis. Surgery to remove the primary cancer or metastasis is usually not recommended for treating metastatic cancer. However, in the era of novel immune checkpoint therapy (ICT), it is not known whether surgery can be safely combined with ICT to provide survival benefit for patients with metastatic cancer. Therefore, we designed a prospective, randomized, pilot clinical trial with a combination of surgery and different forms of ICT for the treatment of patients with metastatic renal cell carcinoma (RCC). Patients on this trial received ICT followed by cytoreductive surgery (CRS) consisting of nephrectomy (removal of primary tumor in the kidney) or metastasectomy (removal of metastatic lesions), or to biopsy (not counted as CRS) then continued with maintenance ICT for up to 2 years. Our data indicate that CRS can be safely combined with ICT without increasing surgical complications. For patients who had CRS plus ICT, 2-year overall survival (OS) rate is 86% and median OS has not yet been reached with median follow-up of 36.8 months. For patients who only received ICT, 2-year OS rate is 48% and median OS is 20.1 months. We have also identified a number of potential genomic and immunologic biomarkers that correlate with clinical benefits. Our study represents an initial pilot trial to demonstrate the feasibility of combining surgery with ICT for patients with metastatic disease. This combination approach warrants additional studies to improve clinical outcomes for patients with metastatic cancers.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004434","title":"The Egyptian Collaborative Cardiac Genomics (ECCO-GEN) Project: Defining a Healthy Volunteer Cohort","description":"The integration of comprehensive genomic and phenotypic data from diverse ethnic populations offers unprecedented opportunities towards advancements in precision medicine and novel diagnostic technologies. Current reference genomic databases are not representative of the global human population, making variant interpretation challenging, especially in underrepresented populations such as the North African population. To address this, the Egyptian Collaborative Cardiac Genomics (ECCO-GEN) Project launched a study comprising 1000 individuals free of cardiovascular disease (CVD). Here, we present the first 391 Egyptian healthy volunteers (EHVols) recruited to establish a pilot phenotyped control cohort. All individuals underwent detailed clinical investigation, including cardiac MRI, and were sequenced using a targeted panel of 174 genes with reported roles in inherited cardiac conditions (ICC). We identified 1,262 variants in 27 cardiomyopathy genes of which 15.1% were not captured in current global and regional genetic reference databases (here: gnomAD and Great Middle Eastern (GME) Variome). The ECCO-GEN project aims at defining the genetic landscape of an understudied population and providing individual-level genetic and phenotypic data to support future studies in CVD and population genetics.","abstract":"The integration of comprehensive genomic and phenotypic data from diverse ethnic populations offers unprecedented opportunities towards advancements in precision medicine and novel diagnostic technologies. Current reference genomic databases are not representative of the global human population, making variant interpretation challenging, especially in underrepresented populations such as the North African population. To address this, the Egyptian Collaborative Cardiac Genomics (ECCO-GEN) Project launched a study comprising 1000 individuals free of cardiovascular disease (CVD). Here, we present the first 391 Egyptian healthy volunteers (EHVols) recruited to establish a pilot phenotyped control cohort. All individuals underwent detailed clinical investigation, including cardiac MRI, and were sequenced using a targeted panel of 174 genes with reported roles in inherited cardiac conditions (ICC). We identified 1,262 variants in 27 cardiomyopathy genes of which 15.1% were not captured in current global and regional genetic reference databases (here: gnomAD and Great Middle Eastern (GME) Variome). The ECCO-GEN project aims at defining the genetic landscape of an understudied population and providing individual-level genetic and phenotypic data to support future studies in CVD and population genetics.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-19T03:56:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004435","title":"DO NOT USE - Whole genome sequencing of SI-NETs from five patients","description":"Small intestine neuroendocrine tumor (SI-NET), the most common cancer of the small bowel, often displays a curious multifocal phenotype with several intestinal tumors centered around a regional lymph node metastasis, yet the typical path of evolution of these lesions remains unclear. Here, we determined the complete genome sequences of 37 tumors from 5 patients with multifocal SI-NET, allowing elucidation of phylogenetic relationships between multiple intestinal tumors and metastases in individual patients.","abstract":"Small intestine neuroendocrine tumor (SI-NET), the most common cancer of the small bowel, often displays a curious multifocal phenotype with several intestinal tumors centered around a regional lymph node metastasis, yet the typical path of evolution of these lesions remains unclear. Here, we determined the complete genome sequences of 37 tumors from 5 patients with multifocal SI-NET, allowing elucidation of phylogenetic relationships between multiple intestinal tumors and metastases in individual patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-19T15:15:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004436","title":"Highlighted samples from the BCH CRDC","description":"These exomes are from some of the patients and family members detailed in our forthcoming publication, Children’s Rare Disease Cohorts: an integrative research and clinical genomics initiative. While this paper details an institutional collection of exomes, the samples here were specifically highlighted as having significant findings.","abstract":"These exomes are from some of the patients and family members detailed in our forthcoming publication, Children’s Rare Disease Cohorts: an integrative research and clinical genomics initiative. While this paper details an institutional collection of exomes, the samples here were specifically highlighted as having significant findings.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-19T14:27:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004437","title":"Deep sequencing of the gut microbiome from 946 healthy donors of the Milieu Intérieur cohort","description":"In this study, we aim to determine, in a thousand healthy donors, how the profile and dynamics of the gut microbiome are affected by host factors such as sex, age and lifestyle parameters.","abstract":"In this study, we aim to determine, in a thousand healthy donors, how the profile and dynamics of the gut microbiome are affected by host factors such as sex, age and lifestyle parameters.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-20T13:53:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004438","title":"Immunogenomics of colorectal cancer response to immune checkpoint blockade","description":"Molecular and cellular determinants of response to immune checkpoint inhibitors are mostly unknown. Here we use whole exome, RNA and T cell receptor sequencing, imaging mass cytometry, immunohistochemistry and PD1-PDL1 interaction detection to profile 543 regions from 16 colorectal cancers (CRCs) subsequently treated with Pembrolizumab or Nivolumab. Independent of treatment response, CRCs express low levels of PD1 and PDL1 proteins and form less PD1-PDL1 complex than other cancers. Non hypermutated CRCs have no benefit from treatment, show WNT activation and low T cell infiltrates. Among hypermutated CRCs, those with durable benefit have clonal immunogenic alterations, clonally expanded T cells and potential for immune escape through dysfunctional antigen presentation. Responsive tumours are enriched in PD1-expressing cytotoxic and proliferating CD8 T cells and PDL1-expressing antigen presenting macrophages, which form high-density clusters of interacting cells. Our study shows that immune checkpoint inhibitors are most effective in highly infiltrated CRCs where they may release the interactions between macrophages and CD8 T cells thus promoting their priming and expansion in intra-tumour niches.","abstract":"Molecular and cellular determinants of response to immune checkpoint inhibitors are mostly unknown. Here we use whole exome, RNA and T cell receptor sequencing, imaging mass cytometry, immunohistochemistry and PD1-PDL1 interaction detection to profile 543 regions from 16 colorectal cancers (CRCs) subsequently treated with Pembrolizumab or Nivolumab. Independent of treatment response, CRCs express low levels of PD1 and PDL1 proteins and form less PD1-PDL1 complex than other cancers. Non hypermutated CRCs have no benefit from treatment, show WNT activation and low T cell infiltrates. Among hypermutated CRCs, those with durable benefit have clonal immunogenic alterations, clonally expanded T cells and potential for immune escape through dysfunctional antigen presentation. Responsive tumours are enriched in PD1-expressing cytotoxic and proliferating CD8 T cells and PDL1-expressing antigen presenting macrophages, which form high-density clusters of interacting cells. Our study shows that immune checkpoint inhibitors are most effective in highly infiltrated CRCs where they may release the interactions between macrophages and CD8 T cells thus promoting their priming and expansion in intra-tumour niches.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-20T20:50:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004439","title":"Patient-derived organoids as a novel tool to study cervical cancer","description":"Cervical cancer is the most prevalent gynecological malignancy worldwide, often caused by infection with a high-risk human papillomavirus. Currently, there are only limited number of human-derived culture systems available that enable to study the viral infection for short-term. Here, we report on establishment of long-term human-derived organoid cultures from both healthy ecto- and endocervical epithelia that closely recapitulate the tissues of origin by maintaining the authentic histological and tissue-specific gene expression profiles. Additionally, using material from patients’ Pap-brush material, a successful panel of long-term patient-derived cancer organoids was established that maintain the causative viral infection in vitro and show differential response to common chemotherapy regimens. This study provides a promising platform for cervical cancer research and studying direct virus-host interactions.","abstract":"Cervical cancer is the most prevalent gynecological malignancy worldwide, often caused by infection with a high-risk human papillomavirus. Currently, there are only limited number of human-derived culture systems available that enable to study the viral infection for short-term. Here, we report on establishment of long-term human-derived organoid cultures from both healthy ecto- and endocervical epithelia that closely recapitulate the tissues of origin by maintaining the authentic histological and tissue-specific gene expression profiles. Additionally, using material from patients’ Pap-brush material, a successful panel of long-term patient-derived cancer organoids was established that maintain the causative viral infection in vitro and show differential response to common chemotherapy regimens. This study provides a promising platform for cervical cancer research and studying direct virus-host interactions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-21T09:00:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004440","title":"Single-cell DNA amplicon sequencing reveals clonal heterogeneity and evolution in T-cell acute lymphoblastic leukemia","description":"T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive leukemia that is most frequent in children and is characterized by the presence of few chromosomal rearrangements and 10 to 20 somatic mutations in protein-coding regions at diagnosis. The majority of T-ALL cases harbor activating mutations in NOTCH1 together with mutations in genes implicated in kinase signaling, transcriptional regulation or protein translation. To obtain more insight in the level of clonal heterogeneity at diagnosis and during treatment, we used single-cell targeted DNA sequencing with the Tapestri platform. We designed a custom ALL panel and obtained accurate single-nucleotide variant and small insertion-deletion mutation calling for 305 amplicons covering 110 genes in about 4400 cells per sample and time point. A total of 108,188 cells were analyzed for 25 samples of 8 T-ALL patients. We typically observed a major clone at diagnosis (&gt;35% of the cells) accompanied by several minor clones of which some were less than 1% of the total number of cells. Four patients had &gt;2 NOTCH1 mutations some of which present in minor clones, indicating a strong pressure to acquire NOTCH1 mutations in developing T-ALL cells. By analyzing longitudinal samples, we detected the presence and clonal nature of residual leukemic cells as well as clones with a minor presence at diagnosis that evolved to clinically relevant major clones at later disease stages. Single-cell DNA amplicon sequencing is a sensitive assay to detect clonal architecture and evolution in T-ALL.","abstract":"T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive leukemia that is most frequent in children and is characterized by the presence of few chromosomal rearrangements and 10 to 20 somatic mutations in protein-coding regions at diagnosis. The majority of T-ALL cases harbor activating mutations in NOTCH1 together with mutations in genes implicated in kinase signaling, transcriptional regulation or protein translation. To obtain more insight in the level of clonal heterogeneity at diagnosis and during treatment, we used single-cell targeted DNA sequencing with the Tapestri platform. We designed a custom ALL panel and obtained accurate single-nucleotide variant and small insertion-deletion mutation calling for 305 amplicons covering 110 genes in about 4400 cells per sample and time point. A total of 108,188 cells were analyzed for 25 samples of 8 T-ALL patients. We typically observed a major clone at diagnosis (&gt;35% of the cells) accompanied by several minor clones of which some were less than 1% of the total number of cells. Four patients had &gt;2 NOTCH1 mutations some of which present in minor clones, indicating a strong pressure to acquire NOTCH1 mutations in developing T-ALL cells. By analyzing longitudinal samples, we detected the presence and clonal nature of residual leukemic cells as well as clones with a minor presence at diagnosis that evolved to clinically relevant major clones at later disease stages. Single-cell DNA amplicon sequencing is a sensitive assay to detect clonal architecture and evolution in T-ALL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-21T13:36:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004441","title":"Post_Mortem_Tissue_COVID19_spatial","description":"Single cell analysis of post mortem tissue samples from SARS-CoV2-infected patients\n\nWe aim to directly identify the human cell types infected by SARS-CoV-2 and measure the cellular response to COVID19 infection across 20 different tissues from infected patient autopsies. We have examined the expression pattern of viral entry receptors across healthy human tissues to predict  several candidate target cell types across the airway and heart. In addition, high prevalence of cardiac failure and abnormal renal function in COVID19 patients implicates heart and kidney involvement, but the pathogenesis of organ specific damage - whether via a direct cytopathic mechanism or an indirect inflammatory response - remains unknown . Currently, we lack confirmation of target cell types and cellular processes in infected tissues as autopsies are discouraged in most countries due to health and safety risks. Our collaborators Drs Michael Osborn and Brian Hanley (Imperial College) have outlined guidelines to perform post-mortem in COVID19 patients (Hanley et al., 2020) and have established a programme of autopsies for research to be performed in a high-risk facility at Westminster Public Mortuary. Here, we propose to identify infected cell types and aberrant molecular pathologies in this precious tissue resource using single cell and spatial genomics. We will prioritise three organ systems: the human airway, heart and the kidney. We will directly examine the cellular identities of SARS-CoV-2 infected cell types and identify the cellular responses to infection across these organs. This fundamental knowledge will help guide future treatment choices for COVID19.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Single cell analysis of post mortem tissue samples from SARS-CoV2-infected patients\n\nWe aim to directly identify the human cell types infected by SARS-CoV-2 and measure the cellular response to COVID19 infection across 20 different tissues from infected patient autopsies. We have examined the expression pattern of viral entry receptors across healthy human tissues to predict  several candidate target cell types across the airway and heart. In addition, high prevalence of cardiac failure and abnormal renal function in COVID19 patients implicates heart and kidney involvement, but the pathogenesis of organ specific damage - whether via a direct cytopathic mechanism or an indirect inflammatory response - remains unknown . Currently, we lack confirmation of target cell types and cellular processes in infected tissues as autopsies are discouraged in most countries due to health and safety risks. Our collaborators Drs Michael Osborn and Brian Hanley (Imperial College) have outlined guidelines to perform post-mortem in COVID19 patients (Hanley et al., 2020) and have established a programme of autopsies for research to be performed in a high-risk facility at Westminster Public Mortuary. Here, we propose to identify infected cell types and aberrant molecular pathologies in this precious tissue resource using single cell and spatial genomics. We will prioritise three organ systems: the human airway, heart and the kidney. We will directly examine the cellular identities of SARS-CoV-2 infected cell types and identify the cellular responses to infection across these organs. This fundamental knowledge will help guide future treatment choices for COVID19.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-21T15:54:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004442","title":"Post_Mortem_Tissue_COVID19_RNA","description":"Single cell analysis of post mortem tissue samples from SARS-CoV2-infected patients\n\nWe aim to directly identify the human cell types infected by SARS-CoV-2 and measure the cellular response to COVID19 infection across 20 different tissues from infected patient autopsies. We have examined the expression pattern of viral entry receptors across healthy human tissues to predict  several candidate target cell types across the airway and heart. In addition, high prevalence of cardiac failure and abnormal renal function in COVID19 patients implicates heart and kidney involvement, but the pathogenesis of organ specific damage - whether via a direct cytopathic mechanism or an indirect inflammatory response - remains unknown . Currently, we lack confirmation of target cell types and cellular processes in infected tissues as autopsies are discouraged in most countries due to health and safety risks. Our collaborators Drs Michael Osborn and Brian Hanley (Imperial College) have outlined guidelines to perform post-mortem in COVID19 patients (Hanley et al., 2020) and have established a programme of autopsies for research to be performed in a high-risk facility at Westminster Public Mortuary. Here, we propose to identify infected cell types and aberrant molecular pathologies in this precious tissue resource using single cell and spatial genomics. We will prioritise three organ systems: the human airway, heart and the kidney. We will directly examine the cellular identities of SARS-CoV-2 infected cell types and identify the cellular responses to infection across these organs. This fundamental knowledge will help guide future treatment choices for COVID19.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Single cell analysis of post mortem tissue samples from SARS-CoV2-infected patients\n\nWe aim to directly identify the human cell types infected by SARS-CoV-2 and measure the cellular response to COVID19 infection across 20 different tissues from infected patient autopsies. We have examined the expression pattern of viral entry receptors across healthy human tissues to predict  several candidate target cell types across the airway and heart. In addition, high prevalence of cardiac failure and abnormal renal function in COVID19 patients implicates heart and kidney involvement, but the pathogenesis of organ specific damage - whether via a direct cytopathic mechanism or an indirect inflammatory response - remains unknown . Currently, we lack confirmation of target cell types and cellular processes in infected tissues as autopsies are discouraged in most countries due to health and safety risks. Our collaborators Drs Michael Osborn and Brian Hanley (Imperial College) have outlined guidelines to perform post-mortem in COVID19 patients (Hanley et al., 2020) and have established a programme of autopsies for research to be performed in a high-risk facility at Westminster Public Mortuary. Here, we propose to identify infected cell types and aberrant molecular pathologies in this precious tissue resource using single cell and spatial genomics. We will prioritise three organ systems: the human airway, heart and the kidney. We will directly examine the cellular identities of SARS-CoV-2 infected cell types and identify the cellular responses to infection across these organs. This fundamental knowledge will help guide future treatment choices for COVID19.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-21T15:58:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004443","title":"Single-cell analysis for metastatic gastric adenocarcinoma","description":"Intra-tumoral heterogeneity (ITH) is the fundamental property of cancer, however, the origins of ITH remain poorly understood. Here we performed single-cell RNA sequencing of peritoneal carcinomatosis (PC) from patients with advanced gastric adenocarcinoma (GAC), constructed a transcriptome map of 45,048 PC cells, profiled the transcriptome states of diverse tumor cell lineages and types, incisively explored ITH of PC tumor cells, and identified significant correlates with patient survival.","abstract":"Intra-tumoral heterogeneity (ITH) is the fundamental property of cancer, however, the origins of ITH remain poorly understood. Here we performed single-cell RNA sequencing of peritoneal carcinomatosis (PC) from patients with advanced gastric adenocarcinoma (GAC), constructed a transcriptome map of 45,048 PC cells, profiled the transcriptome states of diverse tumor cell lineages and types, incisively explored ITH of PC tumor cells, and identified significant correlates with patient survival.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-21T16:36:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004444","title":"Immunogenomic landscape of hematological malignancies","description":"We integrated over 8,000 transcriptomes and over 2,000 samples with multilevel genomic data of hematological cancers to investigate how immunological features are linked to cancer subtypes, genetic and epigenetic alterations, and patient survival. For more detailed follow-up analyses in acute myeloid leukemia (AML), single-cell RNA sequencing was performed on 8 AML bone marrow samples at diagnosis to profile the phenotypes of blasts and infiltrating immune cells in different disease subtypes.","abstract":"We integrated over 8,000 transcriptomes and over 2,000 samples with multilevel genomic data of hematological cancers to investigate how immunological features are linked to cancer subtypes, genetic and epigenetic alterations, and patient survival. For more detailed follow-up analyses in acute myeloid leukemia (AML), single-cell RNA sequencing was performed on 8 AML bone marrow samples at diagnosis to profile the phenotypes of blasts and infiltrating immune cells in different disease subtypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-21T17:24:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004445","title":"Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial","description":"ABACUS is a single arm phase 2 study that investigated 2 cycles of atezolizumab (1200mg Q3) prior to cystectomy in 95 patients with muscle invasive transitional cell cancer (T2-4N0M0). Pathological complete response (pCR) occurring in ≥20% of patients was the primary endpoint. Biomarker analysis on sequential tissue was a co-primary endpoint.","abstract":"ABACUS is a single arm phase 2 study that investigated 2 cycles of atezolizumab (1200mg Q3) prior to cystectomy in 95 patients with muscle invasive transitional cell cancer (T2-4N0M0). Pathological complete response (pCR) occurring in ≥20% of patients was the primary endpoint. Biomarker analysis on sequential tissue was a co-primary endpoint.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-22T00:37:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004446","title":"ctDNA monitoring using patient-specific sequencing and integration of variant reads - Breast cohort","description":"Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of &gt;105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to individual parts per million. This resulted in median Area Under the Curve (AUC) values of 0.98 in advanced cancers, and 0.80 in early stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that the INVAR may be applied without requiring personalized sequencing panels, so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.","abstract":"Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of &gt;105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to individual parts per million. This resulted in median Area Under the Curve (AUC) values of 0.98 in advanced cancers, and 0.80 in early stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that the INVAR may be applied without requiring personalized sequencing panels, so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-22T15:20:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004447","title":"ctDNA monitoring using patient-specific sequencing and integration of variant reads - Lung cohort","description":"Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of &gt;105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to individual parts per million. This resulted in median Area Under the Curve (AUC) values of 0.98 in advanced cancers, and 0.80 in early stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that the INVAR may be applied without requiring personalized sequencing panels, so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.","abstract":"Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of &gt;105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to individual parts per million. This resulted in median Area Under the Curve (AUC) values of 0.98 in advanced cancers, and 0.80 in early stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that the INVAR may be applied without requiring personalized sequencing panels, so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-22T15:25:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004448","title":"Clonal fitness inferred from timeseries modeling of single cell cancer genomes","description":"Progress in defining genomic fitness landscapes in cancer by copy  number alterations (CNA) has been impeded by lack of single cell and timeseries sampling. We generated 42,000 single cell whole genomes (scWGS) from breast epithelium and primary triple negative breast cancer (TNBC) patient-derived xenografts  (PDX) collected during multi-year time series. Using a Wright-Fisher population genetics model, we inferred reproducible CNA-defined clonal fitness dynamics induced by TP53 mutation and cisplatin chemotherapy, with accurate forecasting of experimentally enforced clonal competition dynamics. Drug treatment in three long-term serially passaged TNBC PDX resulted in cisplatin resistant clones that had shown low fitness in the untreated setting. By contrast high fitness clones from treatment naive controls were eradicated reflecting an inversion of the fitness landscape.  Upon drug release selective pressure dynamics were reversed indicating a fitness cost of treatment resistance. Taken together, our findings reveal clonal fitness dynamics linked to CNA and therapeutic resistance in polyclonal tumours.","abstract":"Progress in defining genomic fitness landscapes in cancer by copy  number alterations (CNA) has been impeded by lack of single cell and timeseries sampling. We generated 42,000 single cell whole genomes (scWGS) from breast epithelium and primary triple negative breast cancer (TNBC) patient-derived xenografts  (PDX) collected during multi-year time series. Using a Wright-Fisher population genetics model, we inferred reproducible CNA-defined clonal fitness dynamics induced by TP53 mutation and cisplatin chemotherapy, with accurate forecasting of experimentally enforced clonal competition dynamics. Drug treatment in three long-term serially passaged TNBC PDX resulted in cisplatin resistant clones that had shown low fitness in the untreated setting. By contrast high fitness clones from treatment naive controls were eradicated reflecting an inversion of the fitness landscape.  Upon drug release selective pressure dynamics were reversed indicating a fitness cost of treatment resistance. Taken together, our findings reveal clonal fitness dynamics linked to CNA and therapeutic resistance in polyclonal tumours.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-22T21:19:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004449","title":"Single cell sequencing in CNS autoimmune disease","description":null,"abstract":"Immunophenotyping of T and B cells infiltrating teratomas associated with NMDAR antibody associated encephalitis and paired peripheral blood samples.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-23T20:09:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004450","title":"Suppressive granulocytes are an indicator of severe disease in COVID-19","description":null,"abstract":"Severe Acute Respiratory Syndrome - Coronavirus-2’ (SARS-CoV-2) infection causes Coronavirus Disease 2019 (COVID-19), a mild to moderate respiratory infection in the majority of patients. A subset of COVID-19 patients, however, progresses to severe disease and acute respiratory failure, typically in the second week of the disease. Dysregulated immune responses have been observed in severe COVID-19 and increased neutrophil counts have been associated with clinical deterioration. The mechanisms of protective immunity in mild forms and dysregulated inflammation in severe courses of COVID-19 remain unclear. Here, we combined two single-cell RNA-sequencing technologies and single-cell proteomics in whole blood and PBMC to determine changes in immune cell composition and -activation in two independent cohorts of patients with either mild or severe forms of COVID-19.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004451","title":"Single cell RNAseq of PBMC from RCC patients","description":"Frozen PBMC samples containing at least 1 million cells were thawed for 1 minute at 37C and washed twice with RPMI complete media (10% FBS with glutamate and Pen/Strep). All of the samples had &amp;gt;80% viable cells. Sample processing for single-cell RNA-seq was done using Chromium Single Cell 3’ Library and Gel bead kit v2 (PN-120237) following manufacturer’s user guide (CG00052, 10x Genomics, Pleasanton, CA). The total cell density was used to impute the volume of single cell suspension needed in the reverse transcription (RT) master mix, aiming to achieve ~ 6,000 cells per sample. cDNAs and libraries were prepared following manufacturer’s user guide (10x Genomics). cDNA amplification and indexed libraries were prepared using 12 and 14 cycles of PCR, respectively. Libraries were profiled, quantified, and sequenced as 5’ single-cell gene expression libraries.","abstract":"Frozen PBMC samples containing at least 1 million cells were thawed for 1 minute at 37C and washed twice with RPMI complete media (10% FBS with glutamate and Pen/Strep). All of the samples had &amp;gt;80% viable cells. Sample processing for single-cell RNA-seq was done using Chromium Single Cell 3’ Library and Gel bead kit v2 (PN-120237) following manufacturer’s user guide (CG00052, 10x Genomics, Pleasanton, CA). The total cell density was used to impute the volume of single cell suspension needed in the reverse transcription (RT) master mix, aiming to achieve ~ 6,000 cells per sample. cDNAs and libraries were prepared following manufacturer’s user guide (10x Genomics). cDNA amplification and indexed libraries were prepared using 12 and 14 cycles of PCR, respectively. Libraries were profiled, quantified, and sequenced as 5’ single-cell gene expression libraries.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-24T23:45:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004452","title":"FOXM1 is a biomarker of resistance to PI3Kα inhibition in ER+ breast cancer that is detectable using metabolic imaging (RNA-seq data)","description":"PIK3CA, encoding the PI3Kα isoform, is the most frequently mutated oncogene in estrogen receptor-positive breast cancer. Isoform-selective PI3K inhibitors are used clinically but intrinsic and acquired resistance limits their utility. Improved selection of patients that will benefit from these drugs requires novel predictive biomarkers. We show here that persistent FOXM1 expression following drug treatment is a biomarker of resistance to PI3Kα inhibition in ER+ breast cancer.  Since the transcription factor drives expression of lactate dehydrogenase (LDH) but not hexokinase 2 (HK-II), changes in FOXM1 expression can be detected using magnetic resonance imaging of LDH-catalyzed hyperpolarized 13C label exchange between pyruvate and lactate but not by PET measurements of HK-II-mediated trapping of the glucose analog 2-deoxy-2-[18F]fluorodeoxyglucose.","abstract":"PIK3CA, encoding the PI3Kα isoform, is the most frequently mutated oncogene in estrogen receptor-positive breast cancer. Isoform-selective PI3K inhibitors are used clinically but intrinsic and acquired resistance limits their utility. Improved selection of patients that will benefit from these drugs requires novel predictive biomarkers. We show here that persistent FOXM1 expression following drug treatment is a biomarker of resistance to PI3Kα inhibition in ER+ breast cancer.  Since the transcription factor drives expression of lactate dehydrogenase (LDH) but not hexokinase 2 (HK-II), changes in FOXM1 expression can be detected using magnetic resonance imaging of LDH-catalyzed hyperpolarized 13C label exchange between pyruvate and lactate but not by PET measurements of HK-II-mediated trapping of the glucose analog 2-deoxy-2-[18F]fluorodeoxyglucose.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-24T23:59:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004453","title":"Elderly microbiome from the Bruneck study","description":"Here, we study 304 fecal samples collected from the elderly subjects in Italy.","abstract":"Here, we study 304 fecal samples collected from the elderly subjects in Italy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004454","title":"A molecular signature for IL-10-producing Th1 cells in protozoan parasitic diseases","description":"Control of the intracellular parasites that cause malaria and visceral leishmaniasis (VL) is dependent on the generation of pro-inflammatory, IFNγ+ Tbet+ CD4+ T (Th1) cells by infected hosts. Immunoregulatory IL-10 produced by Th1 cells serves to mitigate subsequent inflammation and related disease pathology. However, these IL-10-producing Th1 (Tr1) cells can also not only promote parasite persistence, but may impair immunity to re-infection and potential vaccine efficacy. Here, we identify molecular and phenotypic signatures that distinguish Th1 cells from Tr1 cells in both experimental VL, caused by infection of C57BL/6 mice with the human parasite Leishmania donovani, and in Plasmodium falciparum-infected humans participating in controlled human malaria infection (CHMI) studies. Such characterisations allow for the better understanding of Tr1 cell development and function in the context of these parasitic diseases, and for the identification of targets for immune modulation to improve anti-parasitic immunity.","abstract":"Control of the intracellular parasites that cause malaria and visceral leishmaniasis (VL) is dependent on the generation of pro-inflammatory, IFNγ+ Tbet+ CD4+ T (Th1) cells by infected hosts. Immunoregulatory IL-10 produced by Th1 cells serves to mitigate subsequent inflammation and related disease pathology. However, these IL-10-producing Th1 (Tr1) cells can also not only promote parasite persistence, but may impair immunity to re-infection and potential vaccine efficacy. Here, we identify molecular and phenotypic signatures that distinguish Th1 cells from Tr1 cells in both experimental VL, caused by infection of C57BL/6 mice with the human parasite Leishmania donovani, and in Plasmodium falciparum-infected humans participating in controlled human malaria infection (CHMI) studies. Such characterisations allow for the better understanding of Tr1 cell development and function in the context of these parasitic diseases, and for the identification of targets for immune modulation to improve anti-parasitic immunity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-26T05:35:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004455","title":"CRISPR/Cas9-mediated genome editing of Schistosoma mansoni acetylcholinesterase","description":"Here we report successful gene knock-in (KI) in the eggs of Schistosoma mansoni by combining CRISPR/Cas9 with single-stranded oligodeoxynucleotides (ssODNs). We targeted the acetylcholinesterase (AChE) gene of S. mansoni using two synthetic guide RNAs (gRNAs), X5 and X7, respectively. Liver eggs of S. mansoni were exposed to CRISPR-vector containing X5 or X7 by electroporation. Simultaneously, eggs were transfected with a ssODN donor encoding a stop codon in all six frames. Next generation sequencing analysis revealed that CRISPR/Cas9-mediated editing in S. mansoni eggs resulted in Homology-Directed Repair (HDR) when template DNA ssODN provided. Furthermore, soluble egg antigen (SEA) from AChE-modified eggs exhibited markedly reduced AChE activity compared with controls, indicative that programmed Cas9 cleavage mutated the AChE gene. Following injection of modified schistosome eggs into the tail veins of mice, a significant decrease in granuloma size in the lungs of these animals. Notably, an enhanced Th2 response induced by eggs in lung, and splenocytes small intestine-draining mesenteric lymph node cells was also generated in mice injected with X5-KI eggs in different methods. These findings further demonstrate the power and utility of CRISPR/Cas9-based genome editing for undertaking functional genomics studies in schistosomes.","abstract":"Here we report successful gene knock-in (KI) in the eggs of Schistosoma mansoni by combining CRISPR/Cas9 with single-stranded oligodeoxynucleotides (ssODNs). We targeted the acetylcholinesterase (AChE) gene of S. mansoni using two synthetic guide RNAs (gRNAs), X5 and X7, respectively. Liver eggs of S. mansoni were exposed to CRISPR-vector containing X5 or X7 by electroporation. Simultaneously, eggs were transfected with a ssODN donor encoding a stop codon in all six frames. Next generation sequencing analysis revealed that CRISPR/Cas9-mediated editing in S. mansoni eggs resulted in Homology-Directed Repair (HDR) when template DNA ssODN provided. Furthermore, soluble egg antigen (SEA) from AChE-modified eggs exhibited markedly reduced AChE activity compared with controls, indicative that programmed Cas9 cleavage mutated the AChE gene. Following injection of modified schistosome eggs into the tail veins of mice, a significant decrease in granuloma size in the lungs of these animals. Notably, an enhanced Th2 response induced by eggs in lung, and splenocytes small intestine-draining mesenteric lymph node cells was also generated in mice injected with X5-KI eggs in different methods. These findings further demonstrate the power and utility of CRISPR/Cas9-based genome editing for undertaking functional genomics studies in schistosomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-26T05:38:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004456","title":"Comparative analysis of somatic variant calling on matched FF and FFPE WGS samples","description":"This study aims at assessing whether FFPE material can be used for cohort analysis. To this end, we performed an in-depth comparison of somatic SNVs called on matching FF and FFPE whole genome sequences samples extracted from the same metastatic prostate tumor. \nFour variant callers were used to call somatic variants on both the FF and the FFPE samples. An heuristic was developed to maximize the overlap between the FF and its FFPE counterparts. Then, the extent to which intra-tumor heterogeneity explains discrepancies in variants called between the FF and the FFPE samples was assessed by comparing the clonal and subclonal somatic variants. \nThis study illustrates that when using the correct variant calling strategy, the majority of clonal SNVs can be recovered in an FFPE sample with high precision and sensitivity. These results suggest that somatic variants derived from WGS of FFPE material can be used in cohort studies.","abstract":"This study aims at assessing whether FFPE material can be used for cohort analysis. To this end, we performed an in-depth comparison of somatic SNVs called on matching FF and FFPE whole genome sequences samples extracted from the same metastatic prostate tumor. \nFour variant callers were used to call somatic variants on both the FF and the FFPE samples. An heuristic was developed to maximize the overlap between the FF and its FFPE counterparts. Then, the extent to which intra-tumor heterogeneity explains discrepancies in variants called between the FF and the FFPE samples was assessed by comparing the clonal and subclonal somatic variants. \nThis study illustrates that when using the correct variant calling strategy, the majority of clonal SNVs can be recovered in an FFPE sample with high precision and sensitivity. These results suggest that somatic variants derived from WGS of FFPE material can be used in cohort studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-26T16:52:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004457","title":"ARID1A Mutation plus CXCL13 Expression Act as Combinatorial Biomarkers to Predict Responses to Immune Checkpoint Therapy in mUCC","description":"A combination of genomic mutation of ARID1A and expression of immune cytokine CXCL13 in the baseline tumor tissues improve predictive outcomes for patients with metastatic urothelial carcinoma receiving ICT, highlighting the fact that combination biomarker approaches may be more important than single biomarkers in predicting clinical responses.\n\nPublication:\n\nGoswami et al. ARID1A mutation plus CXCL13 expression act as combinatorial biomarkers to predict responses to immune checkpoint therapy in mUCC. Science Translational Medicine  17 Jun 2020:\nVol. 12, Issue 548, eabc4220. DOI: 10.1126/scitranslmed.abc4220","abstract":"A combination of genomic mutation of ARID1A and expression of immune cytokine CXCL13 in the baseline tumor tissues improve predictive outcomes for patients with metastatic urothelial carcinoma receiving ICT, highlighting the fact that combination biomarker approaches may be more important than single biomarkers in predicting clinical responses.\n\nPublication:\n\nGoswami et al. ARID1A mutation plus CXCL13 expression act as combinatorial biomarkers to predict responses to immune checkpoint therapy in mUCC. Science Translational Medicine  17 Jun 2020:\nVol. 12, Issue 548, eabc4220. DOI: 10.1126/scitranslmed.abc4220","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004458","title":"Single cell RNAseq of PBMC from bladder cancer patients","description":null,"abstract":"Frozen PBMC samples containing at least 1 million cells were thawed for 1 minute at 37C and washed twice with RPMI complete media (10% FBS with glutamate and Pen/Strep). All of the samples had &amp;gt;80% viable cells. Sample processing for single-cell RNA-seq was done using Chromium Single Cell 3’ Library and Gel bead kit v2 (PN-120237) following manufacturer’s user guide (CG00052, 10x Genomics, Pleasanton, CA). The total cell density was used to impute the volume of single cell suspension needed in the reverse transcription (RT) master mix, aiming to achieve ~ 6,000 cells per sample. cDNAs and libraries were prepared following manufacturer’s user guide (10x Genomics). cDNA amplification and indexed libraries were prepared using 12 and 14 cycles of PCR, respectively. Libraries were profiled, quantified, and sequenced as 5’ single-cell gene expression libraries.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-27T18:11:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004459","title":"Khoe-San genomes reveal unique variation and confirm deepest population divergence in Homo sapiens","description":"The southern African indigenous Khoe-San populations harbor the most divergent lineages of all living peoples. Exploring their genomes is key to understanding deep human history. We sequenced 25 full genomes from five Khoe-San populations, revealing many novel variants, that 25% of variants are unique to the Khoe-San, and that the Khoe-San group harbors the greatest level of diversity across the globe. In line with previous studies, we found several gene-regions with extreme values in genome-wide distributions, potentially caused by natural selection early in the modern human lineage and more recent in time. These gene-regions included immunity-, sperm-, brain-, diet- and muscle-related genes. When accounting for recent admixture, all Khoe-San groups display genetic diversity approaching the levels in other African groups and a reduction in effective population size starting around 100,000 years ago. Hence, all human groups show a reduction in effective population size commencing around the time of the Out-of-Africa migrations, which coincides with changes in the paleoclimate records, changes that potentially impacted all humans at the time.","abstract":"The southern African indigenous Khoe-San populations harbor the most divergent lineages of all living peoples. Exploring their genomes is key to understanding deep human history. We sequenced 25 full genomes from five Khoe-San populations, revealing many novel variants, that 25% of variants are unique to the Khoe-San, and that the Khoe-San group harbors the greatest level of diversity across the globe. In line with previous studies, we found several gene-regions with extreme values in genome-wide distributions, potentially caused by natural selection early in the modern human lineage and more recent in time. These gene-regions included immunity-, sperm-, brain-, diet- and muscle-related genes. When accounting for recent admixture, all Khoe-San groups display genetic diversity approaching the levels in other African groups and a reduction in effective population size starting around 100,000 years ago. Hence, all human groups show a reduction in effective population size commencing around the time of the Out-of-Africa migrations, which coincides with changes in the paleoclimate records, changes that potentially impacted all humans at the time.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-28T07:58:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004460","title":"Modulation of macrophage inflammatory function through selective inhibition of the epigenetic reader protein SP140","description":"SP140 is a bromodomain-containing protein expressed predominantly in immune cells. Genetic polymorphisms and epigenetic modifications in the SP140 locus have been linked to Crohn’s disease (CD), suggesting a role in inflammation. We report the development of the first small molecule SP140 inhibitor (GSK761) and utilize this to elucidate SP140 function in macrophages. We show that SP140 is highly expressed in CD68+ CD mucosal macrophages and in in vitro-generated inflammatory macrophages. SP140 inhibition through GSK761 reduced monocyte differentiation into inflammatory macrophages and lipopolysaccharide (LPS)-induced inflammatory activation. SP140 preferentially occupies transcriptional start sites (TSS) in inflammatory macrophages, with enrichment at gene loci encoding pro-inflammatory cytokines/chemokines and inflammatory pathways. GSK761 specifically reduced SP140 binding and thereby expression of SP140-bound genes. GSK761 inhibited the spontaneous expression of cytokines, including TNF, by CD14+ macrophages isolated from CD intestinal-mucosa. This study identifies SP140 as a druggable epigenetic therapeutic target for CD.","abstract":"SP140 is a bromodomain-containing protein expressed predominantly in immune cells. Genetic polymorphisms and epigenetic modifications in the SP140 locus have been linked to Crohn’s disease (CD), suggesting a role in inflammation. We report the development of the first small molecule SP140 inhibitor (GSK761) and utilize this to elucidate SP140 function in macrophages. We show that SP140 is highly expressed in CD68+ CD mucosal macrophages and in in vitro-generated inflammatory macrophages. SP140 inhibition through GSK761 reduced monocyte differentiation into inflammatory macrophages and lipopolysaccharide (LPS)-induced inflammatory activation. SP140 preferentially occupies transcriptional start sites (TSS) in inflammatory macrophages, with enrichment at gene loci encoding pro-inflammatory cytokines/chemokines and inflammatory pathways. GSK761 specifically reduced SP140 binding and thereby expression of SP140-bound genes. GSK761 inhibited the spontaneous expression of cytokines, including TNF, by CD14+ macrophages isolated from CD intestinal-mucosa. This study identifies SP140 as a druggable epigenetic therapeutic target for CD.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-29T20:49:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004461","title":"Whole-exome sequencing and microRNA profiling predicted relapse risk of stage I lung adenocarcinomas","description":"Despite the advance in precision therapy, about 20% of stage I non-small cell lung cancer patients suffer a relapse after surgical resection. To develop molecular signatures for relapse prediction of stage I lung adenocarcinoma (LUAD), we conduct comprehensive analyses of multiplatform molecular profiling from 113 treatment-naïve stage I Taiwanese LUAD patients. We identify 16 nonsynonymous non-sporadic point mutations (NSPOPMs) harbored at EGFR, KRAS, TP53, CTNNB1 and 6 other genes, and find that the Non-EGFR NSPOPMs were associated with early relapse in a dose-dependent manner via variant allele fraction (VAF). We define a score, maxVAF, to aggregate the VAFs of these NSPOPMs by the maximum value. MicroRNA expression analysis shows a strong correlation between miR-31 and maxVAF. Combining maxVAF with miR-31 led to a powerful risk prediction for surgically resected stage I patients (hazard ratio = 8.65, P = 0.001). Our study opens up more options for precision management of stage I LUAD patients.","abstract":"Despite the advance in precision therapy, about 20% of stage I non-small cell lung cancer patients suffer a relapse after surgical resection. To develop molecular signatures for relapse prediction of stage I lung adenocarcinoma (LUAD), we conduct comprehensive analyses of multiplatform molecular profiling from 113 treatment-naïve stage I Taiwanese LUAD patients. We identify 16 nonsynonymous non-sporadic point mutations (NSPOPMs) harbored at EGFR, KRAS, TP53, CTNNB1 and 6 other genes, and find that the Non-EGFR NSPOPMs were associated with early relapse in a dose-dependent manner via variant allele fraction (VAF). We define a score, maxVAF, to aggregate the VAFs of these NSPOPMs by the maximum value. MicroRNA expression analysis shows a strong correlation between miR-31 and maxVAF. Combining maxVAF with miR-31 led to a powerful risk prediction for surgically resected stage I patients (hazard ratio = 8.65, P = 0.001). Our study opens up more options for precision management of stage I LUAD patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-05-30T02:42:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004462","title":"Mutational_burden_in_human_hair_follicles","description":"We would like to dissect human hair follicles and assess the mutations found in diffferent parts of the follicle eg bulge, root etc.  We can also compare this with mutations found in the surrounding epidermis of the same patients (this is done under a different study).  This may provide insights into the origin of PTCH1 mutants frequently seen in basal cell carcinoma but so far not located in our whole epidermis work as well as defining the clonality of the hair follicle","abstract":"We would like to dissect human hair follicles and assess the mutations found in diffferent parts of the follicle eg bulge, root etc.  We can also compare this with mutations found in the surrounding epidermis of the same patients (this is done under a different study).  This may provide insights into the origin of PTCH1 mutants frequently seen in basal cell carcinoma but so far not located in our whole epidermis work as well as defining the clonality of the hair follicle","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-01T08:23:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004463","title":"Immunoreactive_p53_areas_in_human_skin_2","description":"Previous work has suggested that in mice there may be a difference in mutational burden between areas expressing stabilised p53 protein and others.  We wish to see if this observation holds true in human sun-exposed epidermis.\n  We will take 0.25mm punch biopsies from peeled human skin epidermis which will be submitted to the low input pipeline prior to sequencing.","abstract":"Previous work has suggested that in mice there may be a difference in mutational burden between areas expressing stabilised p53 protein and others.  We wish to see if this observation holds true in human sun-exposed epidermis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-01T10:24:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004464","title":"_WGS__Somatic_mutation_in_skin_epidermis__SMS_","description":"Previously we have sequenced 2mm2 biospies of human epithelia at high depth using a custom bait set.   This has identified a range of mutations.  Some of the biospies are predicted to be clonal and we would like to perform WGS to give an insight into mutational burden, and CNV  which may be associated with these mutations.","abstract":"Previously we have sequenced 2mm2 biospies of human epithelia at high depth using a custom bait set.   This has identified a range of mutations.  Some of the biospies are predicted to be clonal and we would like to perform WGS to give an insight into mutational burden, and CNV  which may be associated with these mutations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-01T10:25:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004465","title":"WGS_skin_punches","description":"We wish to understand the degree of copy number alterations in normal human sun exposed skin.  We have collected small punches of epithelia and using a bait set design have shown the these span a clone.  WGS will provide copy number information on these.","abstract":"We wish to understand the degree of copy number alterations in normal human sun exposed skin.  We have collected small punches of epithelia and using a bait set design have shown the these span a clone.  WGS will provide copy number information on these.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-01T10:25:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004466","title":"Single cell RNA sequencing of normal endometrial derived organoids uncovers novel cell type markers for prognostication","description":"Endometrial carcinoma, the most common gynecologic cancer, develops from endometrial epithelium which is composed of secretory and ciliated cells. Pathologic classification is unreliable and there is a need for prognostic tools. We used single cell sequencing to study organoid model systems derived from normal endometrial endometrium to discover novel markers specific for endometrial ciliated or secretory cells. We performed single cell sequencing on endometrial and ovarian tumors and found both secretory-like and ciliated-like tumor cells.","abstract":"Endometrial carcinoma, the most common gynecologic cancer, develops from endometrial epithelium which is composed of secretory and ciliated cells. Pathologic classification is unreliable and there is a need for prognostic tools. We used single cell sequencing to study organoid model systems derived from normal endometrial endometrium to discover novel markers specific for endometrial ciliated or secretory cells. We performed single cell sequencing on endometrial and ovarian tumors and found both secretory-like and ciliated-like tumor cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-01T20:35:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004467","title":"Initial whole genome sequencing of plasma cell neoplasms in First Responders exposed to the World Trade Center attack of September 11, 2001","description":"The World Trade Center (WTC) attack of September 11, 2001 created an unprecedented environmental exposure to known and suspected carcinogens. High incidence of multiple myeloma (MM) and precursor conditions has been reported among first responders to the WTC disaster. To expand on our prior screening studies, and to characterize the genomic impact of the exposure to known and potential carcinogens in the WTC debris, we were motivated to perform whole genome sequencing (WGS) of WTC first responders and recovery workers who developed a plasma cell disorder after the attack. PATIENTS AND METHODS: We performed WGS of 9 CD138-positive bone marrow mononuclear samples from patients who were diagnosed with plasma cell disorders after the WTC disaster. RESULTS: No significant differences were observed in comparing the post-WTC driver and mutational signatures landscape with 110 previously published WGS from 56 patients with MM and the CoMMpass WGS cohort (n=752). Leveraging constant activity of the single base substitution mutational signatures 1 and 5 over time, we estimated that tumor-initiating chromosomal gains were windowed to both pre- and post-WTC exposure. CONCLUSIONS: Although limitations in sample size preclude any definitive conclusions, our findings suggest that the observed increased incidence of plasma cell neoplasms in this population is due to complex and heterogeneous effects of the WTC exposure that may have initiated or contributed to progression of malignancy.","abstract":"The World Trade Center (WTC) attack of September 11, 2001 created an unprecedented environmental exposure to known and suspected carcinogens. High incidence of multiple myeloma (MM) and precursor conditions has been reported among first responders to the WTC disaster. To expand on our prior screening studies, and to characterize the genomic impact of the exposure to known and potential carcinogens in the WTC debris, we were motivated to perform whole genome sequencing (WGS) of WTC first responders and recovery workers who developed a plasma cell disorder after the attack. PATIENTS AND METHODS: We performed WGS of 9 CD138-positive bone marrow mononuclear samples from patients who were diagnosed with plasma cell disorders after the WTC disaster. RESULTS: No significant differences were observed in comparing the post-WTC driver and mutational signatures landscape with 110 previously published WGS from 56 patients with MM and the CoMMpass WGS cohort (n=752). Leveraging constant activity of the single base substitution mutational signatures 1 and 5 over time, we estimated that tumor-initiating chromosomal gains were windowed to both pre- and post-WTC exposure. CONCLUSIONS: Although limitations in sample size preclude any definitive conclusions, our findings suggest that the observed increased incidence of plasma cell neoplasms in this population is due to complex and heterogeneous effects of the WTC exposure that may have initiated or contributed to progression of malignancy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-01T22:20:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004468","title":"A Single-Cell Atlas of the Multicellular Ecosystem of Primary and Metastatic Hepatocellular Carcinoma","description":"Hepatocellular carcinoma (HCC) represents a paradigm of the relation between tumor microenvironment (TME) and tumor development. Here, we generated a single-cell atlas of the multicellular ecosystem of HCCs from four relevant sites. Antitumor central memory T (TCM) cells were found in tertiary lymphoid structures (TLSs). Chronic HBV/HCV infection increases infiltration of CD8+ T cells in tumors but aggravates T cell exhaustion. We identified CD11b+ macrophages to be terminally differentiated tumor-associated macrophages (TAMs) and two distinct differentiation trajectories contribute to their accumulation. We further demonstrated CD11b+ TAMs promote HCC cells invasion and migration, and angiogenesis. We characterized the heterogeneous subpopulations of malignant hepatocytes and their multifaceted roles in shaping the immune microenvironment. Finally, we identified seven TME subtypes that can predict patient prognosis. Collectively, this large-scale atlas deepens our understanding of the ecosystem in primary and metastatic HCCs, might facilitating the development of new immune therapy strategies for this malignancy.","abstract":"Hepatocellular carcinoma (HCC) represents a paradigm of the relation between tumor microenvironment (TME) and tumor development. Here, we generated a single-cell atlas of the multicellular ecosystem of HCCs from four relevant sites. Antitumor central memory T (TCM) cells were found in tertiary lymphoid structures (TLSs). Chronic HBV/HCV infection increases infiltration of CD8+ T cells in tumors but aggravates T cell exhaustion. We identified CD11b+ macrophages to be terminally differentiated tumor-associated macrophages (TAMs) and two distinct differentiation trajectories contribute to their accumulation. We further demonstrated CD11b+ TAMs promote HCC cells invasion and migration, and angiogenesis. We characterized the heterogeneous subpopulations of malignant hepatocytes and their multifaceted roles in shaping the immune microenvironment. Finally, we identified seven TME subtypes that can predict patient prognosis. Collectively, this large-scale atlas deepens our understanding of the ecosystem in primary and metastatic HCCs, might facilitating the development of new immune therapy strategies for this malignancy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-02T15:05:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004469","title":"Genetic and evolutionary patterns of treatment resistance in relapsed B-cell lymphoma","description":null,"abstract":"Diffuse large B-cell lymphoma (DLBCL) patients are typically treated with immunochemotherapy containing Rituximab; however, prognosis is extremely poor if R-CHOP fails. To identify genetic mechanisms underlying primary or acquired R-CHOP resistance, we performed CAPPSeq on 135 rrDLBCLs, primarily liquid biopsies, as well as 22 relapsed transformed folicular lymphomas. We identified recurrently mutated genes in rrDLBCL, identified genes enriched for mutations upon relapse, and compared the mutation landscape to paired samples obtained prior to therapy to identify mutations which undergo clonal selection following the selective pressure of therapy","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004470","title":"Defective mitophagy and enhanced oxidative stress dictate regulatory T cell impairment in autoimmunity","description":"Regulatory T cell (Treg) impairment is a common denominator of autoimmune pathologies. Despite the extensive characterization of Treg cell phenotype in autoimmunity, the molecular mechanisms underlying their deterioration remain ill defined. To investigate Treg dysfunction during autoimmunity we performed transcriptomic analysis of CD4+CD25highCD127- Treg cells from peripheral blood of patients with autoimmunity.","abstract":"Regulatory T cell (Treg) impairment is a common denominator of autoimmune pathologies. Despite the extensive characterization of Treg cell phenotype in autoimmunity, the molecular mechanisms underlying their deterioration remain ill defined. To investigate Treg dysfunction during autoimmunity we performed transcriptomic analysis of CD4+CD25highCD127- Treg cells from peripheral blood of patients with autoimmunity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-02T21:01:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004471","title":"Genetic Legacy of Punan Hunter-Gatherer Groups in Indonesian Borneo","description":"Punan Batu (the “Cave Punan”), the last living nomadic hunter-gatherer (HG) group who still literally live under karst rock shelters in Borneo, is the least-known hunter-gatherer society in Asia. To provide insights on the origin and adaptation of the Cave Punan, here we present the autosomal genome-wide SNPs study of the Cave Punan, including other Punan groups who speak different language from the Cave Punan, which are transitioning into a more sedentary lifestyle.","abstract":"Punan Batu (the “Cave Punan”), the last living nomadic hunter-gatherer (HG) group who still literally live under karst rock shelters in Borneo, is the least-known hunter-gatherer society in Asia. To provide insights on the origin and adaptation of the Cave Punan, here we present the autosomal genome-wide SNPs study of the Cave Punan, including other Punan groups who speak different language from the Cave Punan, which are transitioning into a more sedentary lifestyle.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004472","title":"Collection of Genotypic and Ethnographic Information from Individuals of South African Ethnic Groups","description":"The hunter-gatherers and pastoralists of South Africa retain the highest genetic diversity of any population. Genetic determinants of light skin pigmentation, reduced stature etc and other basic biomedical phenotypes are unique to samples with Southern African hunter-gatherer and pastoralist ancestry or retain ancestral haplotypes not found in other populations.","abstract":"The hunter-gatherers and pastoralists of South Africa retain the highest genetic diversity of any population. Genetic determinants of light skin pigmentation, reduced stature etc and other basic biomedical phenotypes are unique to samples with Southern African hunter-gatherer and pastoralist ancestry or retain ancestral haplotypes not found in other populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-03T10:29:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004473","title":"Evolutionary analysis of pancreatic neoplastic cysts through whole-exome and targeted sequencing","description":"Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyzed 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing.","abstract":"Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyzed 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-03T13:46:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004474","title":"Peripheral immunoprofiling of stratifies COVID-19 patients based on disease-specific neutrophil signatures","description":null,"abstract":"The SARS-CoV-2 pandemic has led to increasing numbers of COVID-19 patients all over the world. Aetiopathologies range from no symptoms, mild flu-like to severe cases succumbing to respiratory failure. Reports on a dysregulated immune system in the severe cases, showing similarities to cytokine release syndrome, calls for better characterization and understanding of the changes in the immune system as well as their variance across COVID-19 patients in order to be able to design according to host-directed therapies. Here, we profiled blood transcriptomes of 39 COVID-19 patients and 10 control donors. Enriched granulocyte signatures in whole blood samples were verified in granulocyte samples from 49 COVID-19 patients in a second cohort.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004475","title":"Collection of Genotypic and Ethnographic Information from Individuals of South African Ethnic Groups","description":null,"abstract":"The hunter-gatherers and pastoralists of South Africa retain the highest genetic diversity of any population. Genetic determinants of light skin pigmentation, reduced stature etc and other basic biomedical phenotypes are unique to samples with Southern African hunter-gatherer and pastoralist ancestry or retain ancestral haplotypes not found in other populations.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004476","title":"RNA sequencing of subchondral bone from patients that underwent a joint replacement surgery due to osteoarthritis.","description":null,"abstract":"Osteoarthritis (OA) has a considerable genetic component. Genetic research has resulted in many insights into underlying disease pathways. Nonetheless, follow up studies of identified susceptibility genes towards underlying biological mechanisms, preclinical studies on target discovery and eventually drug testing during have thus far focused on gene expression profiling in articular cartilage. Therefore, the aim of the current study was to characterize pathophysiological processes of subchondral bone in human osteoarthritis (OA) in large human cohort RNA sequencing.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-04T09:27:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004477","title":"Versatile workflow for cell-type resolved transcriptional and epigenetic profiles from cryopreserved human lung","description":"The complexity of the lung microenvironment and changes in cellular composition during disease progression make it exceptionally hard to understand molecular mechanisms leading to the development of chronic lung diseases. Although recent advances in cell-type resolved and single-cell sequencing approaches hold great promise for studying complex diseases, their implementation relies on local access to fresh tissue, as traditional tissue storage methods do not allow viable cell isolation.\n\nTo overcome these hurdles, we developed a novel, versatile workflow that allows long-term storage of human lung tissue with high cell viability, permits thorough sample quality check before cell isolation, and is compatible with sequencing-based profiling, including single-cell approaches. We demonstrate that cryopreservation is suitable for the isolation of multiple cell types from human lung and is applicable to both healthy and diseased tissue, including COPD and tumour samples. Basal cells isolated from cryopreserved airways retain the ability to differentiate, indicating that cellular identity is not altered by cryopreservation. Importantly, using RNA sequencing and EPIC Array, we show that genome-wide gene expression and DNA methylation signatures are preserved upon cryopreservation, emphasizing the suitability of our workflow for -omics profiling of human lung cells. In addition, we obtained high-quality single-cell RNA sequencing data of cells isolated from the cryopreserved human lung, demonstrating that cryopreservation empowers single-cell approaches.\n\nOverall, thanks to its simplicity, our cryopreservation workflow is well-suited for prospective tissue collection by academic collaborators and biobanks, opening worldwide access to human tissue.","abstract":"The complexity of the lung microenvironment and changes in cellular composition during disease progression make it exceptionally hard to understand molecular mechanisms leading to the development of chronic lung diseases. Although recent advances in cell-type resolved and single-cell sequencing approaches hold great promise for studying complex diseases, their implementation relies on local access to fresh tissue, as traditional tissue storage methods do not allow viable cell isolation.\n\nTo overcome these hurdles, we developed a novel, versatile workflow that allows long-term storage of human lung tissue with high cell viability, permits thorough sample quality check before cell isolation, and is compatible with sequencing-based profiling, including single-cell approaches. We demonstrate that cryopreservation is suitable for the isolation of multiple cell types from human lung and is applicable to both healthy and diseased tissue, including COPD and tumour samples. Basal cells isolated from cryopreserved airways retain the ability to differentiate, indicating that cellular identity is not altered by cryopreservation. Importantly, using RNA sequencing and EPIC Array, we show that genome-wide gene expression and DNA methylation signatures are preserved upon cryopreservation, emphasizing the suitability of our workflow for -omics profiling of human lung cells. In addition, we obtained high-quality single-cell RNA sequencing data of cells isolated from the cryopreserved human lung, demonstrating that cryopreservation empowers single-cell approaches.\n\nOverall, thanks to its simplicity, our cryopreservation workflow is well-suited for prospective tissue collection by academic collaborators and biobanks, opening worldwide access to human tissue.","study_type":"Other","pubmed_ids":[33630765],"external_links":null,"is_released":true,"released_date":"2020-06-04T10:17:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004478","title":"Identifying the role of ID3 in DNA repair and maintenance of genome integrity","description":"The inhibitor of DNA-binding 3 (ID3) is a transcriptional repressor protein that limits the binding of basic helix­loop-helix (bHLH) transcription factors to DNA. Preliminary results from our lab confirm that cellular depletion of ID3 is associated with an impaired DNA damage response. we hypothesize that ID3 has the potential to epigenetically affect DNA repair. This is based on our observation that upon cellular ID3 knockdown, a reduction of chromatin-bound H4K16ac and H3K36me3.","abstract":"The inhibitor of DNA-binding 3 (ID3) is a transcriptional repressor protein that limits the binding of basic helix­loop-helix (bHLH) transcription factors to DNA. Preliminary results from our lab confirm that cellular depletion of ID3 is associated with an impaired DNA damage response. we hypothesize that ID3 has the potential to epigenetically affect DNA repair. This is based on our observation that upon cellular ID3 knockdown, a reduction of chromatin-bound H4K16ac and H3K36me3.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-09T14:23:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004479","title":"Profiling the unique protective properties of intracranial arterial endothelial cells","description":"Cardiovascular disorders, like atherosclerosis and hypertension, are increasingly known to be associated with vascular cognitive impairment (VCI). In particular, intracranial atherosclerosis is one of the main causes of VCI, although plaque development occurs later in time and is structurally different compared to atherosclerosis in extracranial arteries. Recent data suggest that endothelial cells (ECs) that line the intracranial arteries may exert anti-atherosclerotic effects due to yet unidentified pathways. To gain insights into underlying mechanisms, we isolated post-mortem endothelial cells from both the intracranial basilar artery (BA) and the extracranial common carotid artery (CCA) from the same individual (total of 15 individuals) with laser capture microdissection. RNA sequencing revealed a distinct molecular signature of the two endothelial cell populations of which the most prominent ones were validated by means of qPCR. Our data reveal for the first time that intracranial artery ECs exert an immune quiescent phenotype. Secondly, genes known to be involved in the response of ECs to damage (inflammation, differentiation, adhesion, proliferation, permeability and oxidative stress) are differentially expressed in intracranial ECs compared to extracranial ECs. Finally, Desmoplakin (DSP) and Hop Homeobox (HOPX), two genes expressed at a higher level in intracranial ECs, and Sodium Voltage-Gated Channel Beta Subunit 3 (SCN3B), a gene expressed at a lower level in intracranial ECs compared to extracranial ECs, were shown to be responsive to shear stress and/or hypoxia. With our data we present a set of intracranial-specific endothelial genes that may contribute to its protective phenotype, thereby supporting proper perfusion and consequently may preserve cognitive function. Deciphering the molecular regulation of the vascular bed in the brain may lead to the identification of novel potential intervention strategies to halt vascular associated disorders, such as atherosclerosis and vascular cognitive dysfunction.","abstract":"Cardiovascular disorders, like atherosclerosis and hypertension, are increasingly known to be associated with vascular cognitive impairment (VCI). In particular, intracranial atherosclerosis is one of the main causes of VCI, although plaque development occurs later in time and is structurally different compared to atherosclerosis in extracranial arteries. Recent data suggest that endothelial cells (ECs) that line the intracranial arteries may exert anti-atherosclerotic effects due to yet unidentified pathways. To gain insights into underlying mechanisms, we isolated post-mortem endothelial cells from both the intracranial basilar artery (BA) and the extracranial common carotid artery (CCA) from the same individual (total of 15 individuals) with laser capture microdissection. RNA sequencing revealed a distinct molecular signature of the two endothelial cell populations of which the most prominent ones were validated by means of qPCR. Our data reveal for the first time that intracranial artery ECs exert an immune quiescent phenotype. Secondly, genes known to be involved in the response of ECs to damage (inflammation, differentiation, adhesion, proliferation, permeability and oxidative stress) are differentially expressed in intracranial ECs compared to extracranial ECs. Finally, Desmoplakin (DSP) and Hop Homeobox (HOPX), two genes expressed at a higher level in intracranial ECs, and Sodium Voltage-Gated Channel Beta Subunit 3 (SCN3B), a gene expressed at a lower level in intracranial ECs compared to extracranial ECs, were shown to be responsive to shear stress and/or hypoxia. With our data we present a set of intracranial-specific endothelial genes that may contribute to its protective phenotype, thereby supporting proper perfusion and consequently may preserve cognitive function. Deciphering the molecular regulation of the vascular bed in the brain may lead to the identification of novel potential intervention strategies to halt vascular associated disorders, such as atherosclerosis and vascular cognitive dysfunction.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-09T15:38:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004480","title":"The gut microbiota in prediabetes and diabetes: a population-based cross-sectional study","description":"The link between the gut microbiota and type 2 diabetes (T2D) warrants further investigation because of known confounding effects from antidiabetic treatment. Here we profiled the gut microbiome in a discovery (n=1011) and validation (n=484) cohort comprising Swedish subjects naive for diabetes treatment and grouped by glycemic status.","abstract":"The link between the gut microbiota and type 2 diabetes (T2D) warrants further investigation because of known confounding effects from antidiabetic treatment. Here we profiled the gut microbiome in a discovery (n=1011) and validation (n=484) cohort comprising Swedish subjects naive for diabetes treatment and grouped by glycemic status.","study_type":"Other","pubmed_ids":[32652044],"external_links":null,"is_released":true,"released_date":"2020-06-10T10:54:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004481","title":"Single-cell analysis of airway samples identifies immune cell activation correlating with COVID-19 disease severity","description":"To investigate the immune response and mechanisms associated with severe COVID-19, we performed single-cell RNA-seq on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from 5 healthy controls. We identified airway epithelial cell types and states vulnerable to SARS-CoV-2 infection. In COVID-19 patients, epithelial cells showed an average threefold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared with moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand–receptor expression profiles, and activated immune cells , including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF . The transcriptional differences in critical cases compared with moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways may suppress immune hyperactivation in critical COVID-19.","abstract":"To investigate the immune response and mechanisms associated with severe COVID-19, we performed single-cell RNA-seq on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from 5 healthy controls. We identified airway epithelial cell types and states vulnerable to SARS-CoV-2 infection. In COVID-19 patients, epithelial cells showed an average threefold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared with moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand–receptor expression profiles, and activated immune cells , including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF . The transcriptional differences in critical cases compared with moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways may suppress immune hyperactivation in critical COVID-19.","study_type":"Other","pubmed_ids":[32591762],"external_links":null,"is_released":true,"released_date":"2020-06-10T21:07:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004482","title":"Mutational Landscape of Grey Zone Lymphoma","description":"The mutational landscape of grey zone lymphoma (GZL) has not yet been established and differences to related entities are mostly unknown. Here, we studied coding sequence mutations of 50 EBV-negative GZL and 20 polymorphic EBV-positive DLBCL NOS (poly-EBV-L) in comparison to classical Hodgkin lymphoma (cHL), primary mediastinal B cell lymphoma (PMBCL), and diffuse large B cell lymphoma (DLBCL). Paired exomes of 21 GZL and 7 poly-EBV-L cases were analyzed as a discovery cohort followed by targeted sequencing of 217 genes in an extension cohort of 29 GZL and 13 poly-EBV-L cases. GZL cases with thymic niche involvement displayed a mutation profile closely resembling cHL and PMBCL, with SOCS1 (45%), B2M (45%), TNFAIP3 (35%), GNA13 (35%) and NFKBIA (29%) being the most recurrently mutated genes. In contrast, GZL cases without thymic niche involvement (N=18) had a significantly distinct pattern, enriched in mutations related to apoptosis defects (TP53 (39%), BCL2 (28%), BIRC6 (22%)) and depleted in GNA13, XPO1 or NFKB signaling pathway mutations (TNFAIP3, NFKBIE, IKBKB, NFKBIA). Poly-EBV-L cases presented a distinct mutational profile including STAT3, PRKDC mutations and a significantly lower coding-mutation load in comparison to EBV-negative GZL. Our study highlights characteristic mutational patterns in GZL associated with presentation in the thymic niche suggesting a common cell of origin and disease evolution with related anterior mediastinal lymphomas.","abstract":"The mutational landscape of grey zone lymphoma (GZL) has not yet been established and differences to related entities are mostly unknown. Here, we studied coding sequence mutations of 50 EBV-negative GZL and 20 polymorphic EBV-positive DLBCL NOS (poly-EBV-L) in comparison to classical Hodgkin lymphoma (cHL), primary mediastinal B cell lymphoma (PMBCL), and diffuse large B cell lymphoma (DLBCL). Paired exomes of 21 GZL and 7 poly-EBV-L cases were analyzed as a discovery cohort followed by targeted sequencing of 217 genes in an extension cohort of 29 GZL and 13 poly-EBV-L cases. GZL cases with thymic niche involvement displayed a mutation profile closely resembling cHL and PMBCL, with SOCS1 (45%), B2M (45%), TNFAIP3 (35%), GNA13 (35%) and NFKBIA (29%) being the most recurrently mutated genes. In contrast, GZL cases without thymic niche involvement (N=18) had a significantly distinct pattern, enriched in mutations related to apoptosis defects (TP53 (39%), BCL2 (28%), BIRC6 (22%)) and depleted in GNA13, XPO1 or NFKB signaling pathway mutations (TNFAIP3, NFKBIE, IKBKB, NFKBIA). Poly-EBV-L cases presented a distinct mutational profile including STAT3, PRKDC mutations and a significantly lower coding-mutation load in comparison to EBV-negative GZL. Our study highlights characteristic mutational patterns in GZL associated with presentation in the thymic niche suggesting a common cell of origin and disease evolution with related anterior mediastinal lymphomas.","study_type":"Other","pubmed_ids":[32961552],"external_links":null,"is_released":true,"released_date":"2020-06-10T23:42:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004483","title":"Adult T cell leukemia/lymphoma targeted sequencing","description":null,"abstract":"Adult T-cell leukemia/lymphoma (ATL) carries a poor prognosis even in indolent subtypes. We performed targeted deep sequencing of 61 ATL patients of African and Caribbean origin. This revealed mutations mainly affecting TCR/NF-kB (73%), T-cell trafficking (46%), immune-escape (29%) and cell-cycle (26%) related pathways, consistent with the genomic landscape previously reported in a large Japanese cohort.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004484","title":"Single-cell sequencing of gammadelta and CD8+ alphabeta TCR sequences from blood and gut in coeliac disease","description":"Single-cell sequencing of gammadelta and CD8+ alphabeta TCR sequences from blood and gut in coeliac disease, before and during gluten challenge (Samples from baseline, day 6 and day 14 blood, and from baseline + day 14 gut). (Paired end, amplicon sequencing).","abstract":"Single-cell sequencing of gammadelta and CD8+ alphabeta TCR sequences from blood and gut in coeliac disease, before and during gluten challenge (Samples from baseline, day 6 and day 14 blood, and from baseline + day 14 gut). (Paired end, amplicon sequencing).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-11T18:21:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004485","title":"EORTC RP1335 SPECTA Lung cancer data","description":"SPECTAlung has recruited patients with thoracic malignancies, collecting FFPE material for molecular analysis. Illumina TST170 NGS panel was used for sequencing.\nThe goal was to identify patients for whom a personalized treatment was possible and build a clinically-annotated molecular database for thoracic patients.","abstract":"SPECTAlung has recruited patients with thoracic malignancies, collecting FFPE material for molecular analysis. Illumina TST170 NGS panel was used for sequencing.\nThe goal was to identify patients for whom a personalized treatment was possible and build a clinically-annotated molecular database for thoracic patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-12T13:52:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004486","title":"Whole exome sequencing of long-term, never relapse exceptional responders of trastuzumab-treated HER2+ metastatic breast cancer","description":"Trastuzumab has significantly improved the overall survival of patients with HER2+ metastatic breast cancer (MBC). However, outcomes can vary, with patients progressing within 1-year of treatment or exceptional cases of complete response to trastuzumab for ≥ 10 years. Identification of the underlying genomic aberrations of “exceptional responders (ExRs)” compared to “rapid non-responders (NR)” increases our understanding of the mechanisms involved in MBC progression and identification of biomarkers of trastuzumab response and resistance. Whole exome sequencing was performed on six ExRs compared to five NR. The overall fraction of genome copy number alteration (CNA) burden was higher in NR patients (P=0.07), while more significantly pronounced in copy number gains (P=0.03) in NR compared to ExRs. Delineation of the distribution of CNA burden across the genome identified a greater degree of CNA burden in NR within chr8 (P=0.02) and in chr17 (P=0.06) and conferred a statistically significant benefit in overall survival.","abstract":"Trastuzumab has significantly improved the overall survival of patients with HER2+ metastatic breast cancer (MBC). However, outcomes can vary, with patients progressing within 1-year of treatment or exceptional cases of complete response to trastuzumab for ≥ 10 years. Identification of the underlying genomic aberrations of “exceptional responders (ExRs)” compared to “rapid non-responders (NR)” increases our understanding of the mechanisms involved in MBC progression and identification of biomarkers of trastuzumab response and resistance. Whole exome sequencing was performed on six ExRs compared to five NR. The overall fraction of genome copy number alteration (CNA) burden was higher in NR patients (P=0.07), while more significantly pronounced in copy number gains (P=0.03) in NR compared to ExRs. Delineation of the distribution of CNA burden across the genome identified a greater degree of CNA burden in NR within chr8 (P=0.02) and in chr17 (P=0.06) and conferred a statistically significant benefit in overall survival.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-12T16:28:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004487","title":"Blood_and_tissue_with_mild_and_severe_COVID19","description":"Single cell molecular signatures in blood and tissues from mild and severe COVID19 patients\n\nCOVID-19 causes severe respiratory disease requiring mechanical ventilation in approx. 5% of infected patients, with a mortality of 50-60%. Insight into the pathophysiology of this disease is urgently needed to inform treatment decisions. Age and comorbidities are risk factors for death in COVID-19, but young, healthy patients also develop severe COVID-19 requiring prolonged mechanical ventilation.\nKey questions:\n• What immune pathways and cellular phenotypic states distinguish COVID-19 severity?\n• How do immune cell populations in blood and lung relate in severe COVID-19?\nAims:\n• To uncover immune signatures underlying severe disease, revealing candidate immune\npathways involved in pathogenesis\n• Identify candidate predictive biomarkers for larger scale studies\n• Rapidly provide robust in vivo evidence to guide therapeutic intervention\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Single cell molecular signatures in blood and tissues from mild and severe COVID19 patients\n\nCOVID-19 causes severe respiratory disease requiring mechanical ventilation in approx. 5% of infected patients, with a mortality of 50-60%. Insight into the pathophysiology of this disease is urgently needed to inform treatment decisions. Age and comorbidities are risk factors for death in COVID-19, but young, healthy patients also develop severe COVID-19 requiring prolonged mechanical ventilation.\nKey questions:\n• What immune pathways and cellular phenotypic states distinguish COVID-19 severity?\n• How do immune cell populations in blood and lung relate in severe COVID-19?\nAims:\n• To uncover immune signatures underlying severe disease, revealing candidate immune\npathways involved in pathogenesis\n• Identify candidate predictive biomarkers for larger scale studies\n• Rapidly provide robust in vivo evidence to guide therapeutic intervention\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004488","title":"Longitudinal_Cambridge_Study_COVID19","description":"Investigating tissue immune responses to SARSCoV-2 in live and deceased donors\n\nThis project is part of a longitudinal clinical study that will be run from Cambridge University Medical School (Joseph Cheriyen) studying covid-19 infected patients. The Clatworthy project would use single cell approaches to study severe fatal versus non-fatal in old and old versus young patients and will also provide some information on male versus female. This work will provide single cell resolution insights into immune response to the virus, providing vital information on the biology of covid-19 infection.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Investigating tissue immune responses to SARSCoV-2 in live and deceased donors\n\nThis project is part of a longitudinal clinical study that will be run from Cambridge University Medical School (Joseph Cheriyen) studying covid-19 infected patients. The Clatworthy project would use single cell approaches to study severe fatal versus non-fatal in old and old versus young patients and will also provide some information on male versus female. This work will provide single cell resolution insights into immune response to the virus, providing vital information on the biology of covid-19 infection.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-16T12:47:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004489","title":"Autoimmunity_and_immunodeficiency_COVID19","description":"Cell Atlas of COVID-19 patients with Pre-existing Autoimmunity and Immunodeficiency conditions\n\nCOVID-19 disease is characterized by hyperinflammation of the lungs and poor immune response against the virus, leading to acute respiratory distress syndrome. Patients with pre-existing medical conditions strongly correlated with poorer clinical outcomes upon SARS-CoV-2 infection. This study aims to characterize the cellular response to SARS-CoV-2 infection in controls and in patients with primary immunodeficiency and autoimmune disease.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Cell Atlas of COVID-19 patients with Pre-existing Autoimmunity and Immunodeficiency conditions\n\nCOVID-19 disease is characterized by hyperinflammation of the lungs and poor immune response against the virus, leading to acute respiratory distress syndrome. Patients with pre-existing medical conditions strongly correlated with poorer clinical outcomes upon SARS-CoV-2 infection. This study aims to characterize the cellular response to SARS-CoV-2 infection in controls and in patients with primary immunodeficiency and autoimmune disease.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-16T12:55:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004490","title":"HSC_population_dynamics___KX008_samples","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-16T16:21:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004491","title":"A higher ctDNA fraction decreases survival in regorafenib-treated metastatic colorectal cancer patients","description":"The predictive effect of circulating tumor DNA (ctDNA) in colorectal cancer (CRC) treatment is still highly discussed. The primary objective of this study was to investigate a possible prognostic/predictive value of ctDNA under regorafenib treatment. This prospective multicenter translational biomarker phase II pilot study enrolled 30 metastatic CRC patients (67% men, 33% women) treated with regorafenib. ctDNA was assessed in plasma before treatment start and at defined time points during administration. Measurement of tumor fraction as well as mutation and copy number analysis of CRC driver genes were performed by next generation sequencing approaches. Multivariate analyses for survival and treatment efficacy were adjusted to age, gender and ECOG. Disease control rate was 30%. Median tumor fraction at baseline was 18.5% (0-49.9). Mutations in CRC driver genes or genes involved in angiogenesis were identified in 25 patients (83.3%). KRAS mutations were detected in 13 out of 14 KRAS positive tumors, in three patients without KRAS mutation in the respective tumor acquired mutations as a consequence of prior anti-EGFR treatment were detected. In a subset of patients, novel occurring mutations or focal amplifications were detected. A tumor fraction of 5% and higher at baseline was significantly associated with a decreased OS (p=0.022; HHR 3.110 (95%CI: 1.2-8.2). ctDNA is detectable in a high proportion of mCRC patients. Higher ctDNA levels are associated with survival among regorafenib treatment. Moreover, our data highlight the benefit of a combined evaluation of mutations and somatic copy number alterations (SCNA) in advanced cancer patients.","abstract":"The predictive effect of circulating tumor DNA (ctDNA) in colorectal cancer (CRC) treatment is still highly discussed. The primary objective of this study was to investigate a possible prognostic/predictive value of ctDNA under regorafenib treatment. This prospective multicenter translational biomarker phase II pilot study enrolled 30 metastatic CRC patients (67% men, 33% women) treated with regorafenib. ctDNA was assessed in plasma before treatment start and at defined time points during administration. Measurement of tumor fraction as well as mutation and copy number analysis of CRC driver genes were performed by next generation sequencing approaches. Multivariate analyses for survival and treatment efficacy were adjusted to age, gender and ECOG. Disease control rate was 30%. Median tumor fraction at baseline was 18.5% (0-49.9). Mutations in CRC driver genes or genes involved in angiogenesis were identified in 25 patients (83.3%). KRAS mutations were detected in 13 out of 14 KRAS positive tumors, in three patients without KRAS mutation in the respective tumor acquired mutations as a consequence of prior anti-EGFR treatment were detected. In a subset of patients, novel occurring mutations or focal amplifications were detected. A tumor fraction of 5% and higher at baseline was significantly associated with a decreased OS (p=0.022; HHR 3.110 (95%CI: 1.2-8.2). ctDNA is detectable in a high proportion of mCRC patients. Higher ctDNA levels are associated with survival among regorafenib treatment. Moreover, our data highlight the benefit of a combined evaluation of mutations and somatic copy number alterations (SCNA) in advanced cancer patients.","study_type":"Other","pubmed_ids":[32949150],"external_links":null,"is_released":true,"released_date":"2020-06-16T15:53:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004492","title":"Fine-Scale Genomic Analyses Of Admixed Individuals Reveal Unrecognized Genetic Ancestry Components In Argentina","description":"Study the sub-continental origins of African, European and Native American genetic ancestries of Argentinean populations.","abstract":"Study the sub-continental origins of African, European and Native American genetic ancestries of Argentinean populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-17T11:01:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004493","title":"GPMP6","description":null,"abstract":"To provide information on the tumor immune environment and identify combinations of neoantigens specific to recurrent GBM cells that can be used as targets for the immunotherapy being developed","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004494","title":"Cabozantinib Response in ETV6-NTRK3 G623R Positive Carcinoma HIPO-021","description":"We report a case of marked response to cabozantinib in a secondary entrectinib-resistant tumor harboring the ETV6-NTRK3 fusion with a G623R solvent-front mutation.","abstract":"We report a case of marked response to cabozantinib in a secondary entrectinib-resistant tumor harboring the ETV6-NTRK3 fusion with a G623R solvent-front mutation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-18T17:11:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004495","title":"Targets of MEK inhibition in DIPG","description":"The survival of children with diffuse intrinsic pontine glioma (DIPG) remains dismal, with new treatments desperately needed. In the era of precision medicine, targeted therapies represent an exciting treatment opportunity, yet resistance can rapidly emerge, playing an important role in treatment failure. In a prospective biopsy-stratified clinical trial, we combined detailed molecular profiling (methylation BeadArray, exome, RNAseq, phospho-proteomics) linked to drug screening in newly-established patient-derived models of DIPG in vitro and in vivo. We identified a high degree of in vitro sensitivity to the MEK inhibitor trametinib in samples which harboured genetic alterations targeting the MAPK pathway, including the non-canonical BRAF_G469V mutation, and those affecting PIK3R1 and NF1. However, treatment of PDX models and of a patient with trametinib at relapse failed to elicit a significant response. We generated trametinib-resistant clones in the BRAF_G469V model through continuous drug exposure, and identified acquired mutations in MEK1/2 (MEK1_K57N, MEK1_I141S and MEK2_I115N) with sustained pathway up-regulation. These cells showed the hallmarks of mesenchymal transition, and expression signatures overlapping with inherently trametinib-insensitive primary patient-derived cells that predicted an observed sensitivity to dasatinib. Combinations of trametinib with dasatinib and the downstream ERK inhibitor ulixertinib showed highly synergistic effects in vitro. These data highlight the MAPK pathway as a therapeutic target in DIPG, and show the importance of parallel resistance modelling and rational combinatorial treatments likely to be required for meaningful clinical translation.","abstract":"The survival of children with diffuse intrinsic pontine glioma (DIPG) remains dismal, with new treatments desperately needed. In the era of precision medicine, targeted therapies represent an exciting treatment opportunity, yet resistance can rapidly emerge, playing an important role in treatment failure. In a prospective biopsy-stratified clinical trial, we combined detailed molecular profiling (methylation BeadArray, exome, RNAseq, phospho-proteomics) linked to drug screening in newly-established patient-derived models of DIPG in vitro and in vivo. We identified a high degree of in vitro sensitivity to the MEK inhibitor trametinib in samples which harboured genetic alterations targeting the MAPK pathway, including the non-canonical BRAF_G469V mutation, and those affecting PIK3R1 and NF1. However, treatment of PDX models and of a patient with trametinib at relapse failed to elicit a significant response. We generated trametinib-resistant clones in the BRAF_G469V model through continuous drug exposure, and identified acquired mutations in MEK1/2 (MEK1_K57N, MEK1_I141S and MEK2_I115N) with sustained pathway up-regulation. These cells showed the hallmarks of mesenchymal transition, and expression signatures overlapping with inherently trametinib-insensitive primary patient-derived cells that predicted an observed sensitivity to dasatinib. Combinations of trametinib with dasatinib and the downstream ERK inhibitor ulixertinib showed highly synergistic effects in vitro. These data highlight the MAPK pathway as a therapeutic target in DIPG, and show the importance of parallel resistance modelling and rational combinatorial treatments likely to be required for meaningful clinical translation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-19T09:05:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004496","title":"Molecular profiling of patient-derived primary cultures of paediatric high grade glioma and DIPG","description":"Paediatric high grade glioma and diffuse midline glioma (including DIPG) are comprised of multiple biological and clinical subgroups, the majority of which urgently require novel therapies. Patient-derived in vitro primary cell cultures represent potentially useful tools for mechanistic and preclinical investigation based upon their retention of key features of tumour subgroups under experimental conditions amenable to high-throughput approaches. We present 17 novel primary cultures derived from patients in London, Dublin and Belfast, and together with cultures established or shared from Barcelona, Brisbane, Rome and Stanford, assembled a panel of 52 models under 2D (laminin matrix) and/or 3D (neurospheres) conditions, fully credentialed by phenotypic and molecular comparison to the original tumour sample (methylation BeadArray, panel/exome sequencing, RNAseq). In screening a subset of these against a panel of ~400 approved chemotherapeutics and small molecules, we identified specific dependencies associated with tumour subgroups and/or specific molecular markers. These included MYCN-amplified cells and ATM/DNA-PK inhibitors, and DIPGs with PPM1D activating truncating mutations and inhibitors of MDM2 or PARP1. Cells with specific mutations in PDGFRA were found to be highly sensitive to a range of RTK inhibitors, though not all such mutations conferred sensitivity to targeted agents. Notably, dual PDGFRA/FGFR and downstream pathway MEK inhibitors showed profound effects against both PDGFRA-sensitising mutant and FGFR1-dependent non-brainstem pHGG and DIPG. In total, 85% cells were found to have at least one drug screening hit in short term assays linked to the underlying biology of the patient’s tumour, providing a rational approach for individualised clinical translation.","abstract":"Paediatric high grade glioma and diffuse midline glioma (including DIPG) are comprised of multiple biological and clinical subgroups, the majority of which urgently require novel therapies. Patient-derived in vitro primary cell cultures represent potentially useful tools for mechanistic and preclinical investigation based upon their retention of key features of tumour subgroups under experimental conditions amenable to high-throughput approaches. We present 17 novel primary cultures derived from patients in London, Dublin and Belfast, and together with cultures established or shared from Barcelona, Brisbane, Rome and Stanford, assembled a panel of 52 models under 2D (laminin matrix) and/or 3D (neurospheres) conditions, fully credentialed by phenotypic and molecular comparison to the original tumour sample (methylation BeadArray, panel/exome sequencing, RNAseq). In screening a subset of these against a panel of ~400 approved chemotherapeutics and small molecules, we identified specific dependencies associated with tumour subgroups and/or specific molecular markers. These included MYCN-amplified cells and ATM/DNA-PK inhibitors, and DIPGs with PPM1D activating truncating mutations and inhibitors of MDM2 or PARP1. Cells with specific mutations in PDGFRA were found to be highly sensitive to a range of RTK inhibitors, though not all such mutations conferred sensitivity to targeted agents. Notably, dual PDGFRA/FGFR and downstream pathway MEK inhibitors showed profound effects against both PDGFRA-sensitising mutant and FGFR1-dependent non-brainstem pHGG and DIPG. In total, 85% cells were found to have at least one drug screening hit in short term assays linked to the underlying biology of the patient’s tumour, providing a rational approach for individualised clinical translation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004497","title":"Molecular analysis of CRC in patients with Primary Sclerosing Cholangitis (PSC) and Inflammatory Bowel Disease (IBD)","description":null,"abstract":"Patients with both primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) run a 10-fold increased risk of developing colorectal carcinoma (CRC) compared to patients with IBD only. It is unknown which mucosal defects are causing this increased risk. The aim of this study was to investigate which molecular changes give rise to CRC in patients with PSC-IBD, and whether changes occur already in non-dysplastic mucosa.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-19T09:48:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004498","title":"Contemporaneous evolution of chronic lymphocytic leukemia in longitudinal patient samples treated with donor lymphocyte infusion","description":null,"abstract":"We tested a cohort of 24 CLL patients treated with allogeneic stem cell transplant with or without donor lymphocyte infusion. We profiled these patients using whole exome sequencing (WES) of sort-purified CLL before and after DLI, along with matched sorted T-cells as germline samples.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004499","title":"Uterine leiomyoma: DNA methylation, chromatin activity and gene expression","description":"In this study, we observed the effects of different uterine leiomyoma driver mutations to tumor DNA methylation, chromatin activity and gene expression, to form a comprehensive view on the epigenetic consequences of the mutations.","abstract":"In this study, we observed the effects of different uterine leiomyoma driver mutations to tumor DNA methylation, chromatin activity and gene expression, to form a comprehensive view on the epigenetic consequences of the mutations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-22T08:35:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004500","title":"Swarm Learning to identify COVID-19, tuberculosis and leukemia patients based on blood transcriptomes","description":null,"abstract":"Identification of patients with life-threatening diseases including leukemias or infections such as tuberculosis or COVID-19 is an important goal of modern precision medicine. However, there is an increasing divide between what is technically possible and what is allowed because of privacy legislation. We have recently illustrated that classical machine learning can identify leukemia patients based on their blood transcriptomes. To facilitate integration of any omics data from any data owner world-wide without violating privacy laws, we here introduce Swarm Learning (SL), a decentralized machine learning approach uniting edge computing, artificial intelligence (AI), blockchain and privacy protection without the need for a central coordinator thereby going beyond federated learning. To illustrate its feasibility, using more than 12,000 transcriptomes from peripheral blood mononuclear cells and more than 2,000 peripheral blood transcriptomes we demonstrate that SL of omics data distributed across different individual sites leads to disease classifiers that outperform those developed at individual sites. Yet, SL completely protects local privacy regulations by design. We propose this approach to noticeably accelerate the introduction of precision medicine.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004501","title":"Swarm Learning to identify COVID-19, tuberculosis and leukemia patients based on blood transcriptomes","description":null,"abstract":"Identification of patients with life-threatening diseases including leukemias or infections such as tuberculosis or COVID-19 is an important goal of modern precision medicine. However, there is an increasing divide between what is technically possible and what is allowed because of privacy legislation. We have recently illustrated that classical machine learning can identify leukemia patients based on their blood transcriptomes. To facilitate integration of any omics data from any data owner world-wide without violating privacy laws, we here introduce Swarm Learning (SL), a decentralized machine learning approach uniting edge computing, artificial intelligence (AI), blockchain and privacy protection without the need for a central coordinator thereby going beyond federated learning. To illustrate its feasibility, using more than 12,000 transcriptomes from peripheral blood mononuclear cells and more than 2,000 peripheral blood transcriptomes we demonstrate that SL of omics data distributed across different individual sites leads to disease classifiers that outperform those developed at individual sites. Yet, SL completely protects local privacy regulations by design. We propose this approach to noticeably accelerate the introduction of precision medicine.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004502","title":"Swarm Learning to identify COVID-19, tuberculosis and leukemia patients based on blood transcriptomes","description":null,"abstract":"Identification of patients with life-threatening diseases including leukemias or infections such as tuberculosis or COVID-19 is an important goal of modern precision medicine. However, there is an increasing divide between what is technically possible and what is allowed because of privacy legislation. We have recently illustrated that classical machine learning can identify leukemia patients based on their blood transcriptomes. To facilitate integration of any omics data from any data owner world-wide without violating privacy laws, we here introduce Swarm Learning (SL), a decentralized machine learning approach uniting edge computing, artificial intelligence (AI), blockchain and privacy protection without the need for a central coordinator thereby going beyond federated learning. To illustrate its feasibility, using more than 12,000 transcriptomes from peripheral blood mononuclear cells and more than 2,000 peripheral blood transcriptomes we demonstrate that SL of omics data distributed across different individual sites leads to disease classifiers that outperform those developed at individual sites. Yet, SL completely protects local privacy regulations by design. We propose this approach to noticeably accelerate the introduction of precision medicine.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-22T18:30:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004503","title":"Peripheral immunoprofiling of stratifies COVID-19 patients based on disease-specific neutrophil signatures","description":"The SARS-CoV-2 pandemic has led to increasing numbers of COVID-19 patients all over the world. Aetiopathologies range from no symptoms, mild flu-like to severe cases succumbing to respiratory failure. Reports on a dysregulated immune system in the severe cases, showing similarities to cytokine release syndrome, calls for better characterization and understanding of the changes in the immune system as well as their variance across COVID-19 patients in order to be able to design according to host-directed therapies. Here, we profiled blood transcriptomes of 39 COVID-19 patients and 10 control donors. Enriched granulocyte signatures in whole blood samples were verified in granulocyte samples from 49 COVID-19 patients in a second cohort.","abstract":"The SARS-CoV-2 pandemic has led to increasing numbers of COVID-19 patients all over the world. Aetiopathologies range from no symptoms, mild flu-like to severe cases succumbing to respiratory failure. Reports on a dysregulated immune system in the severe cases, showing similarities to cytokine release syndrome, calls for better characterization and understanding of the changes in the immune system as well as their variance across COVID-19 patients in order to be able to design according to host-directed therapies. Here, we profiled blood transcriptomes of 39 COVID-19 patients and 10 control donors. Enriched granulocyte signatures in whole blood samples were verified in granulocyte samples from 49 COVID-19 patients in a second cohort.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-22T23:21:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004504","title":"Human T-bet governs innate and innate-like adaptive IFN-g immunity against mycobacteria.","description":"We report a patient with mycobacterial disease due to inherited deficiency of the transcription factor T-bet. PBMCs from the patient was analyzed with scRNA-seq.","abstract":"We report a patient with mycobacterial disease due to inherited deficiency of the transcription factor T-bet. PBMCs from the patient was analyzed with scRNA-seq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-23T21:24:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004505","title":"RNA-seq data from 121 tumor samples with muscle invasive bladder cancer.","description":"In this study, a total of 300 patients with MIBC receiving chemotherapy were included; 62 received NAC before cystectomy and 245 received first-line chemotherapy upon detection of locally-advanced (T4b) or metastatic disease. Treatment response, defined as pathological downstaging (&lt; pTa,CIS,N0) after NAC or complete or partial response after first-line treatment (RECIST criteria). RNA-seq was performed using the QuantSeq kit FWD HT kit (Lexogen) using 500 ng input RNA from 121 tumor samples. Data provided here consist of 780 fastq files for RNA-seq.","abstract":"In this study, a total of 300 patients with MIBC receiving chemotherapy were included; 62 received NAC before cystectomy and 245 received first-line chemotherapy upon detection of locally-advanced (T4b) or metastatic disease. Treatment response, defined as pathological downstaging (&lt; pTa,CIS,N0) after NAC or complete or partial response after first-line treatment (RECIST criteria). RNA-seq was performed using the QuantSeq kit FWD HT kit (Lexogen) using 500 ng input RNA from 121 tumor samples. Data provided here consist of 780 fastq files for RNA-seq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-24T13:07:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004506","title":"Low-coverage whole-genome sequencing of serial plasma ctDNA","description":null,"abstract":"In this study we have performed low-coverage whole-genome sequencing of plasma ctDNA at serial time points before and during therapy from patients with multiple cancer types.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004507","title":"WES data from 165 tumor/germline samples with muscle invasive bladder cancer.","description":"In this study, a total of 300 patients with MIBC receiving chemotherapy were included; 62 received NAC before cystectomy and 245 received first-line chemotherapy upon detection of locally-advanced (T4b) or metastatic disease. Treatment response, defined as pathological downstaging (&lt; pTa,CIS,N0) after NAC or complete or partial response after first-line treatment (RECIST criteria). WES was performed using DNA from 165 tumors (76x median coverage) and associated germline DNA (46x median coverage). Data provided here consist of 5,828 fastq files for WES.","abstract":"In this study, a total of 300 patients with MIBC receiving chemotherapy were included; 62 received NAC before cystectomy and 245 received first-line chemotherapy upon detection of locally-advanced (T4b) or metastatic disease. Treatment response, defined as pathological downstaging (&lt; pTa,CIS,N0) after NAC or complete or partial response after first-line treatment (RECIST criteria). WES was performed using DNA from 165 tumors (76x median coverage) and associated germline DNA (46x median coverage). Data provided here consist of 5,828 fastq files for WES.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-25T08:52:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004508","title":"Three-dimensional human alveolar stem cell culture models reveal infection response to SARS-CoV-2","description":"Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which is the cause of a present global pandemic, infects human lung alveolar type 2 (hAT2) cells. Characterizing pathogenesis is crucial for developing vaccines and therapeutics. However, the lack of models mirroring the cellular physiology and pathology of hAT2 cells limits the study. Here, we develop a feeder-free, long-term three-dimensional (3D) culture technique for hAT2 cells derived from primary human lung tissue, and investigate infection response to SARS-CoV-2. By imaging-based analysis and single-cell transcriptome profiling, we reveal rapid viral replication and the increased expression of interferon-associated genes and pro-inflammatory genes in infected hAT2 cells, indicating robust endogenous innate immune response. Further tracing of viral mutations acquired during transmission identifies full infection of individual cells effectively from a single viral entry. Our study provides deep insights into the pathogenesis of SARS-CoV-2, and the application of defined 3D hAT2 cultures as models for respiratory diseases.","abstract":"Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which is the cause of a present global pandemic, infects human lung alveolar type 2 (hAT2) cells. Characterizing pathogenesis is crucial for developing vaccines and therapeutics. However, the lack of models mirroring the cellular physiology and pathology of hAT2 cells limits the study. Here, we develop a feeder-free, long-term three-dimensional (3D) culture technique for hAT2 cells derived from primary human lung tissue, and investigate infection response to SARS-CoV-2. By imaging-based analysis and single-cell transcriptome profiling, we reveal rapid viral replication and the increased expression of interferon-associated genes and pro-inflammatory genes in infected hAT2 cells, indicating robust endogenous innate immune response. Further tracing of viral mutations acquired during transmission identifies full infection of individual cells effectively from a single viral entry. Our study provides deep insights into the pathogenesis of SARS-CoV-2, and the application of defined 3D hAT2 cultures as models for respiratory diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-25T15:15:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004509","title":"Profiling of circulating tumor DNA for treatment selection in patients with advanced and refractory carcinoma: A prospective, two-stage phase II individualized cancer treatment trial","description":"Background: Molecular profiling (MP) represents an opportunity to match patients who have exhausted standard lines of treatment to a targeted therapy and circulating tumor DNA (ctDNA) can be harnessed as a non-invasive analyte for this purpose. We evaluated the success of a targeted therapy selected by profiling of ctDNA in patients with advanced and refractory carcinoma.Patients and methods: We obtained a mandatory blood draw as well as an optional tissue biopsy for molecular profiling. Whole-genome sequencing and a cancer hotspot panel were performed and publicly available databases were used to match the molecular profile to targeted treatments. The primary endpoint was the progression-free survival (PFS) ratio (PFS on MP-guided therapy / PFS on the last evidence-based therapy), whereas the success of the targeted therapy was defined as a PFS ratio ≥ 1.2.  To test the impact of molecular profile-treatment matching strategies, we retrospectively analyzed selected cases via the CureMatch PreciGENE™ decision support algorithm.Results: Interim analysis of 24 patients yielded informative results from 20 patients (83%). A potential tumor-specific drug could be matched in 11 patients (46%), eight (33%) received a matched treatment. Median PFS in the matched treatment group was 61.5 days (IQR 49.8-71.0) compared to 81.5 days (IQR 68.5-117.8) for the last evidence-based treatment, resulting in a median PFS ratio of 0.7 (IQR 0.6-0.9). Hence, as no patient experienced a PFS ratio ≥ 1.2, the study was terminated. The retrospective CureMatch analysis identified either a 2-drug or 3-drug combination option in each of the tested cases, including a case for which no therapy was previously identified.Conclusions:Our study is the first to report prospective outcome results on the efficacy of plasma DNA profiling-based treatment, but indicates that more innovative approaches to study design, matching algorithms and drug allocation strategies are necessary to achieve improved patient outcomes.","abstract":"Background: Molecular profiling (MP) represents an opportunity to match patients who have exhausted standard lines of treatment to a targeted therapy and circulating tumor DNA (ctDNA) can be harnessed as a non-invasive analyte for this purpose. We evaluated the success of a targeted therapy selected by profiling of ctDNA in patients with advanced and refractory carcinoma.Patients and methods: We obtained a mandatory blood draw as well as an optional tissue biopsy for molecular profiling. Whole-genome sequencing and a cancer hotspot panel were performed and publicly available databases were used to match the molecular profile to targeted treatments. The primary endpoint was the progression-free survival (PFS) ratio (PFS on MP-guided therapy / PFS on the last evidence-based therapy), whereas the success of the targeted therapy was defined as a PFS ratio ≥ 1.2.  To test the impact of molecular profile-treatment matching strategies, we retrospectively analyzed selected cases via the CureMatch PreciGENE™ decision support algorithm.Results: Interim analysis of 24 patients yielded informative results from 20 patients (83%). A potential tumor-specific drug could be matched in 11 patients (46%), eight (33%) received a matched treatment. Median PFS in the matched treatment group was 61.5 days (IQR 49.8-71.0) compared to 81.5 days (IQR 68.5-117.8) for the last evidence-based treatment, resulting in a median PFS ratio of 0.7 (IQR 0.6-0.9). Hence, as no patient experienced a PFS ratio ≥ 1.2, the study was terminated. The retrospective CureMatch analysis identified either a 2-drug or 3-drug combination option in each of the tested cases, including a case for which no therapy was previously identified.Conclusions:Our study is the first to report prospective outcome results on the efficacy of plasma DNA profiling-based treatment, but indicates that more innovative approaches to study design, matching algorithms and drug allocation strategies are necessary to achieve improved patient outcomes.","study_type":"Other","pubmed_ids":[33717225],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004510","title":"Characterization of four subtypes in morphologically normal tissue excised proximal and distal to breast cancer","description":"Our study provides insight into molecular alterations in HN tissues within the affected breast and offers a greater understanding of the spatial implications of these aberrations. This was achieved by performing a comprehensive analysis of RNA sequencing data and proteomic profiles from breast cancers (n=19) and their matched HN tissues (n=38), healthy breast from cosmetic reduction mammoplasty (RM; n=5), and risk reducing mastectomies (RR, n=5), with peritumoral samples excised at proximal (TP, &lt;2 cm) and distal (TD, 5-10 cm) sites from the primary tumor.","abstract":"Our study provides insight into molecular alterations in HN tissues within the affected breast and offers a greater understanding of the spatial implications of these aberrations. This was achieved by performing a comprehensive analysis of RNA sequencing data and proteomic profiles from breast cancers (n=19) and their matched HN tissues (n=38), healthy breast from cosmetic reduction mammoplasty (RM; n=5), and risk reducing mastectomies (RR, n=5), with peritumoral samples excised at proximal (TP, &lt;2 cm) and distal (TD, 5-10 cm) sites from the primary tumor.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-26T10:54:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004511","title":"Mutator phenotype and specific mutational signature explain an increased risk of hematological malignancies in patients with Xeroderma Pigmentosum","description":"In this study we report for the first time the unique collection of 6 leukemias and two sarcomas from XP-C. Comprehensive WGS-based mutational analysis provides genetic explanation for the increased incidence of leukemia in XP-C and describes an unique mutational process in internal tumors associated with NER deficiency.","abstract":"In this study we report for the first time the unique collection of 6 leukemias and two sarcomas from XP-C. Comprehensive WGS-based mutational analysis provides genetic explanation for the increased incidence of leukemia in XP-C and describes an unique mutational process in internal tumors associated with NER deficiency.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-26T11:34:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004512","title":"A reference map of potential determinants for the human serum metabolome","description":"The collection of metabolites circulating in the human blood, termed the serum metabolome, contains a plethora of biomarkers and causative agents. Although the origin of specific compounds is known, we have a poor understanding of the key determinants of most metabolites. Here, we measured the levels of 1251 circulating metabolites in serum samples from a healthy human cohort of 491 individuals, and devised machine learning algorithms to predict their levels in held-out subjects based on a comprehensive profile consisting of host genetics, gut microbiome, clinical parameters, diet, lifestyle, anthropometric measurements and medication data. Notably, we obtained statistically significant predictions for over 76% of the profiled metabolites. Despite using the strict out-of-sample prediction metric, which is a lower bound for the explained variance, diet and microbiome each explained hundreds of metabolites, with over 50% of the variance explained in some metabolites. We further validated the robustness of the microbiome related associations by showing a high replication rate in two geographically independent cohorts that were not available to us when developing the algorithms. We also demonstrate that some of these interactions are causal, as some metabolites we predicted to be positively associated with bread increased in level following a randomized clinical trial of bread intervention. Microbiome-explained metabolites were enriched with unnamed metabolites, and we devised an algorithm that accurately predicts their biological pathway, finding that they mainly include food components, aromatic amino acids and secondary bile acid derivatives. Overall, our results unravel potential determinants of over 800 metabolites, paving the way towards mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating circulating metabolite levels.","abstract":"The collection of metabolites circulating in the human blood, termed the serum metabolome, contains a plethora of biomarkers and causative agents. Although the origin of specific compounds is known, we have a poor understanding of the key determinants of most metabolites. Here, we measured the levels of 1251 circulating metabolites in serum samples from a healthy human cohort of 491 individuals, and devised machine learning algorithms to predict their levels in held-out subjects based on a comprehensive profile consisting of host genetics, gut microbiome, clinical parameters, diet, lifestyle, anthropometric measurements and medication data. Notably, we obtained statistically significant predictions for over 76% of the profiled metabolites. Despite using the strict out-of-sample prediction metric, which is a lower bound for the explained variance, diet and microbiome each explained hundreds of metabolites, with over 50% of the variance explained in some metabolites. We further validated the robustness of the microbiome related associations by showing a high replication rate in two geographically independent cohorts that were not available to us when developing the algorithms. We also demonstrate that some of these interactions are causal, as some metabolites we predicted to be positively associated with bread increased in level following a randomized clinical trial of bread intervention. Microbiome-explained metabolites were enriched with unnamed metabolites, and we devised an algorithm that accurately predicts their biological pathway, finding that they mainly include food components, aromatic amino acids and secondary bile acid derivatives. Overall, our results unravel potential determinants of over 800 metabolites, paving the way towards mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating circulating metabolite levels.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-28T13:49:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004513","title":"Untargeted serum metabolomics profiled by Metabolon Inc.","description":null,"abstract":"To identify the determinants of the human serum metabolome","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004514","title":"Autism Spectrum Disorders","description":null,"abstract":"We aimed to understand genetic etiology of ASD by next generation Whole genome DNA sequencing.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004515","title":"EPIC arrays data for chemotherapy response project","description":"In this study, a total of 300 patients with MIBC receiving chemotherapy were included; 62 received NAC before cystectomy and 245 received first-line chemotherapy upon detection of locally-advanced (T4b) or metastatic disease. Treatment response, defined as pathological downstaging (&amp;lt; pTa,CIS,N0) after NAC or complete or partial response after first-line treatment (RECIST criteria). DNA methylation analysis was performed using DNA from 72 patients. We used 500 ng genomic DNA for bisulfite conversion followed by whole-genome amplification prior to hybridization to EPIC BeadChip (Illumina, San Diego, CA) overnight as described by the manufacturer and then scanned with the Illumina iSCAN system. Data provided here consist of 144 idat files.","abstract":"In this study, a total of 300 patients with MIBC receiving chemotherapy were included; 62 received NAC before cystectomy and 245 received first-line chemotherapy upon detection of locally-advanced (T4b) or metastatic disease. Treatment response, defined as pathological downstaging (&amp;lt; pTa,CIS,N0) after NAC or complete or partial response after first-line treatment (RECIST criteria). DNA methylation analysis was performed using DNA from 72 patients. We used 500 ng genomic DNA for bisulfite conversion followed by whole-genome amplification prior to hybridization to EPIC BeadChip (Illumina, San Diego, CA) overnight as described by the manufacturer and then scanned with the Illumina iSCAN system. Data provided here consist of 144 idat files.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-29T12:23:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004516","title":"Transcriptomic profiling of lymphedema","description":"RNA-seq of skin from human subjects with and without lymphedema","abstract":"RNA-seq of skin from human subjects with and without lymphedema","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-29T14:49:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004517","title":"Degradation of Cyclin K/CDK12 is a druggable vulnerability of colorectal cancer (H012)","description":null,"abstract":"Here, we screened a library of non-characterized small molecules against CRC patient-derived tumor spheroid culture (TSC) cells to identify a compound (NCT02) with activity in a subset of TSCs. Transcriptomics as well as thermal proteome profiling and chemical proteomics identified degradation of cyclin K (CCNK) and CDK12 as central mechanism-of-action, associated with increase of DNA damage and induction of apoptosis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-29T17:19:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004518","title":"The Molecular Landscape of Asian Breast Cancers Reveals Clinically Relevant Population-Specific Differences","description":"Molecular profiles of breast cancer have contributed to an improved understanding of the disease, enabled development of molecular prognostic signatures to guide treatment decisions and unveiled new or more accurate therapeutic options for breast cancer patients. However, the extent to which differences in genetic, environmental and lifestyle factors influence molecular profiles in different populations remains poorly characterised, as relatively few large-scale molecular studies of breast tumours in non-Caucasian populations have hitherto been reported. Here, we present the molecular profiles of 560 Asian breast tumours and a comparative analysis of breast cancers arising in Asian and Caucasian women. Compared to the breast tumours in predominantly Caucasian women reported in TCGA and METABRIC, we show an increased prevalence of Her2-enriched molecular subtypes and higher prevalence of TP53 somatic mutations in ER+ Asian breast tumours. Using gene expression and immunohistochemistry, we observed elevated immune scores in Asian breast tumours, suggesting potential clinical response to immune checkpoint inhibitors. Whilst Her2-subtype and enriched immune score are associated with improved survival, presence of TP53 somatic mutations is associated with poorer survival in ER+ tumours. Taken together, these population differences unveil new opportunities to improve the understanding of this disease and lay the foundation for precision medicine in different populations.","abstract":"Molecular profiles of breast cancer have contributed to an improved understanding of the disease, enabled development of molecular prognostic signatures to guide treatment decisions and unveiled new or more accurate therapeutic options for breast cancer patients. However, the extent to which differences in genetic, environmental and lifestyle factors influence molecular profiles in different populations remains poorly characterised, as relatively few large-scale molecular studies of breast tumours in non-Caucasian populations have hitherto been reported. Here, we present the molecular profiles of 560 Asian breast tumours and a comparative analysis of breast cancers arising in Asian and Caucasian women. Compared to the breast tumours in predominantly Caucasian women reported in TCGA and METABRIC, we show an increased prevalence of Her2-enriched molecular subtypes and higher prevalence of TP53 somatic mutations in ER+ Asian breast tumours. Using gene expression and immunohistochemistry, we observed elevated immune scores in Asian breast tumours, suggesting potential clinical response to immune checkpoint inhibitors. Whilst Her2-subtype and enriched immune score are associated with improved survival, presence of TP53 somatic mutations is associated with poorer survival in ER+ tumours. Taken together, these population differences unveil new opportunities to improve the understanding of this disease and lay the foundation for precision medicine in different populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-30T09:45:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004519","title":"SNP arrays for chemotherapy response project","description":"In this study, a total of 300 patients with MIBC receiving chemotherapy were included; 62 received NAC before cystectomy and 245 received first-line chemotherapy upon detection of locally-advanced (T4b) or metastatic disease. Treatment response, defined as pathological downstaging (&amp;lt; pTa,CIS,N0) after NAC or complete or partial response after first-line treatment (RECIST criteria). Illumina SNP arrays (760k markers) were performed using DNA from 49 tumors and associated germline DNA (49x median coverage). Data provided here consist of 98 files.","abstract":"In this study, a total of 300 patients with MIBC receiving chemotherapy were included; 62 received NAC before cystectomy and 245 received first-line chemotherapy upon detection of locally-advanced (T4b) or metastatic disease. Treatment response, defined as pathological downstaging (&amp;lt; pTa,CIS,N0) after NAC or complete or partial response after first-line treatment (RECIST criteria). Illumina SNP arrays (760k markers) were performed using DNA from 49 tumors and associated germline DNA (49x median coverage). Data provided here consist of 98 files.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-06-30T10:32:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004520","title":"periscope: sub-genomic RNA identification in SARS-CoV-2 ARTIC Network Nanopore Sequencing Data","description":"We have developed periscope, a tool for the detection and quantification of sub-genomic RNA (sgRNA) in ARTIC network protocol generated Nanopore SARS-CoV-2 sequence data. Applying the tool to 1155 SARS-CoV-2 sequences from Sheffield, UK, we were able to classify and quantify reads arising from canonical and non-canonical sub-genomic RNA. We show that the results are reproducible using technical replicates and that variants found in genomic RNA are transmitted to sub-genomic RNAs with high fidelity in most cases. This tool can be applied to tens of thousands of sequences worldwide to provide the most comprehensive analysis of SARS-CoV-2 sub-genomic RNA to date.\n\nThis study contains data already available in PRJEB37886, however, this study contains reads which have not been length filtered. A pre-requisite for sub-genomic RNA analysis.","abstract":"We have developed periscope, a tool for the detection and quantification of sub-genomic RNA (sgRNA) in ARTIC network protocol generated Nanopore SARS-CoV-2 sequence data. Applying the tool to 1155 SARS-CoV-2 sequences from Sheffield, UK, we were able to classify and quantify reads arising from canonical and non-canonical sub-genomic RNA. We show that the results are reproducible using technical replicates and that variants found in genomic RNA are transmitted to sub-genomic RNAs with high fidelity in most cases. This tool can be applied to tens of thousands of sequences worldwide to provide the most comprehensive analysis of SARS-CoV-2 sub-genomic RNA to date.\n\nThis study contains data already available in PRJEB37886, however, this study contains reads which have not been length filtered. A pre-requisite for sub-genomic RNA analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004521","title":"Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer (NABUCCO Cohorts 1 and 2)","description":null,"abstract":"Preoperative immunotherapy with anti-PD1 plus anti-CTLA4 antibodies has shown remarkable pathological responses in melanoma1 and colorectal cancer2. In NABUCCO (ClinicalTrials.gov: NCT03387761), a single-arm feasibility trial, twenty-four stage III urothelial cancer patients received 2 doses of ipilimumab and 2 doses of nivolumab, followed by resection. The primary endpoint was feasibility to resect &amp;lt;12 weeks from treatment start. All patients were evaluable for the study endpoints and underwent resection; twenty-three (96%) within &amp;lt;12 weeks. Grade 3-4 immune-related adverse events occurred in 55% of patients; 41% when excluding clinically insignificant laboratory abnormalities. 46% of patients had a pathological complete response (pCR), meeting the secondary efficacy endpoint. Fourteen patients (58%) had no remaining invasive disease (pCR or pTisN0/pTaN0). In contrast to studies with anti-PD1/PD-L1 monotherapy, complete response to ipilimumab plus nivolumab was independent of baseline CD8+ presence or T-effector signatures. Induction of TLS upon treatment was observed in responding patients. Our data indicate that combined CTLA-4 plus PD-1 blockade may provide an effective preoperative treatment strategy in locoregionally advanced UC, irrespective of pre-existing CD8+ T-cell activity","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-01T13:16:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004522","title":"Prospective high-throughput genome profiling in advanced cancers","description":"Genomics-based tumor profiling in advanced cancers (aC) was recently demonstrated as feasible in clinical practice. After the prospective pilot PANDORA study done on advanced breast cancers, we conducted a prospective monocenter clinical trial called PERMED01 to evaluate the number patients with locally advanced or metastatic cancer for whom identification of molecular alterations in tumor samples could lead to the delivery of a targeted therapy.","abstract":"Genomics-based tumor profiling in advanced cancers (aC) was recently demonstrated as feasible in clinical practice. After the prospective pilot PANDORA study done on advanced breast cancers, we conducted a prospective monocenter clinical trial called PERMED01 to evaluate the number patients with locally advanced or metastatic cancer for whom identification of molecular alterations in tumor samples could lead to the delivery of a targeted therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004523","title":"An epigenetic single-cell atlas of IDH-mutant glioma reveals the role of ATRX in shaping tumor composition","description":"Recent single-cell RNA-sequencing studies have identified a hierarchy of cell types that is common to all isocitrate dehydrogenase (IDH) -mutant gliomas. This finding is somewhat paradoxical since the genetic differences between IDH-mutant astrocytomas and IDH-mutant oligodendrogliomas are prognostic, predictive of therapeutic response, and correlated with differences in immune infiltrates. To integrate these disparate findings, we constructed a single-cell atlas of 22 human IDH-mutant primary untreated grade-II/III gliomas.","abstract":"Recent single-cell RNA-sequencing studies have identified a hierarchy of cell types that is common to all isocitrate dehydrogenase (IDH) -mutant gliomas. This finding is somewhat paradoxical since the genetic differences between IDH-mutant astrocytomas and IDH-mutant oligodendrogliomas are prognostic, predictive of therapeutic response, and correlated with differences in immune infiltrates. To integrate these disparate findings, we constructed a single-cell atlas of 22 human IDH-mutant primary untreated grade-II/III gliomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-01T18:43:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004524","title":"Changes in alternative splicing and associated neo-antigens due to therapy","description":"Recent studies have identified alternative splicing (AS) as a novel source of neoantigens for immunotherapy. Surprisingly little is known about the AS milieu in recurrent glioblastoma (GBM), despite this being the venue for most clinical trials. We profiled 29 primary-recurrent paired human GBM specimens via RNA sequencing and re-analyzed RNA-sequencing data from non-malignant human brain tissues. From these data, we reconstructed the landscape of AS in GBM through recurrence and contrasted that to isoforms observed in non-malignant brain. The AS events we identified were cross-referenced with single-cell GBM atlases to determine cell-type specific splicing patterns. From this we identified novel splicing events in cell-surface proteins that are suitable targets for engineered T-cell therapies. We found recurrent-specific isoforms of mitogen-activated kinase pathway genes which are expressed exclusively by GBM stem-like cells that enhance invasiveness. These studies shed light on the effect of therapy on AS and identify novel targets for emerging immunotherapies.","abstract":"Recent studies have identified alternative splicing (AS) as a novel source of neoantigens for immunotherapy. Surprisingly little is known about the AS milieu in recurrent glioblastoma (GBM), despite this being the venue for most clinical trials. We profiled 29 primary-recurrent paired human GBM specimens via RNA sequencing and re-analyzed RNA-sequencing data from non-malignant human brain tissues. From these data, we reconstructed the landscape of AS in GBM through recurrence and contrasted that to isoforms observed in non-malignant brain. The AS events we identified were cross-referenced with single-cell GBM atlases to determine cell-type specific splicing patterns. From this we identified novel splicing events in cell-surface proteins that are suitable targets for engineered T-cell therapies. We found recurrent-specific isoforms of mitogen-activated kinase pathway genes which are expressed exclusively by GBM stem-like cells that enhance invasiveness. These studies shed light on the effect of therapy on AS and identify novel targets for emerging immunotherapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-01T18:49:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004525","title":"Multiscale heterogeneity in gastric adenocarcinoma evolution is an obstacle to precision medicine","description":null,"abstract":"Using multiregional sequencing, we tested the effect of somatic evolution on intratumoral heterogeneity and its putative clinical implications in adenocarcinomas of the stomach and gastroesophageal junction (GC). Multiregional whole-exome sequencing was done using 48 tumor samples (range: 4-10 tumor samples/patient) from nine individual patients.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-01T19:30:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004526","title":"Genetic Analysis of Endocrine irAEs in Cancer Patients Treated with PD-1 Checkpoint Inhibitors","description":"Genetic Analysis of Endocrine irAEs in Cancer Patients Treated with PD-1 Checkpoint Inhibitors","abstract":"Genetic Analysis of Endocrine irAEs in Cancer Patients Treated with PD-1 Checkpoint Inhibitors","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004527","title":"WES sequencing of malignant peripheral nerve sheath tumours","description":"Investigate the genomic landscape of MPNST tumours. Cases where a diagnosis of MPNST had been considered in the differential diagnosis with a variable degree of confidence was included. The diagnosis of MPNST was excluded in 12/51 (49 cases had WES data) of the sequenced tumours following review of the pathology, new IHC, molecular tests and clinical information. Article: Lyskjær et al, 2020, J Pathol, \"H3K27me3 expression and methylation status in histological variants of malignant peripheral nerve sheath tumours\".","abstract":"Investigate the genomic landscape of MPNST tumours. Cases where a diagnosis of MPNST had been considered in the differential diagnosis with a variable degree of confidence was included. The diagnosis of MPNST was excluded in 12/51 (49 cases had WES data) of the sequenced tumours following review of the pathology, new IHC, molecular tests and clinical information. Article: Lyskjær et al, 2020, J Pathol, \"H3K27me3 expression and methylation status in histological variants of malignant peripheral nerve sheath tumours\".","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-02T08:05:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004528","title":"RNA seq of MPNST tumour samples","description":"RNA sequencing of 10 MPNST tumour samples as part of a larger study of MPNST. Article: Lyskjær et al, 2020, J Pathol, \"H3K27me3 expression and methylation status in histological variants of malignant peripheral nerve sheath tumours\".","abstract":"RNA sequencing of 10 MPNST tumour samples as part of a larger study of MPNST. Article: Lyskjær et al, 2020, J Pathol, \"H3K27me3 expression and methylation status in histological variants of malignant peripheral nerve sheath tumours\".","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-02T08:05:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004529","title":"Mutational patterns are correlated with malignancy of early stage lung adenocarcinoma in multiple pulmonary nodules","description":"The clinical significance of findings on mutation data from multiple pulmonary nodules is largely limited by single gene mutation-directed analysis as well as lack of validation of gene expression levels. New analysis strategy is urgently needed for comprehensive understanding of these genomic data. We performed whole exome sequencing in 16 multiple lung nodules and 5 adjacent normal tissues from 4 patients and decoded the mutation information from a perspective of cellular functions and pathways. Mutated genes as well as mutation patterns shared in more than two lesions were first identified and characterized. The number of mutations/mutated genes and the extent of protein structural changes caused by different mutation types is positively correlated with the malignancy of the neoplasia. Moreover, the mutated genes in lesion samples tend to converge to certain functions and pathways in relation to cell proliferation and survival, and this converging tendency is stronger in higher level lesions. We showed a developing pattern of quantity (the number of mutations/mutated genes) and quality (the extent of protein structural changes) in early stages of lung adenocarcinoma, as well as a stronger converging tendency in cell proliferation and survival related pathways and functions. Altogether, this study provides a new perspective for comprehension of genomic mutational data and might shed new light on deciphering the molecular evolution of early stage lung adenocarcinoma.","abstract":"The clinical significance of findings on mutation data from multiple pulmonary nodules is largely limited by single gene mutation-directed analysis as well as lack of validation of gene expression levels. New analysis strategy is urgently needed for comprehensive understanding of these genomic data. We performed whole exome sequencing in 16 multiple lung nodules and 5 adjacent normal tissues from 4 patients and decoded the mutation information from a perspective of cellular functions and pathways. Mutated genes as well as mutation patterns shared in more than two lesions were first identified and characterized. The number of mutations/mutated genes and the extent of protein structural changes caused by different mutation types is positively correlated with the malignancy of the neoplasia. Moreover, the mutated genes in lesion samples tend to converge to certain functions and pathways in relation to cell proliferation and survival, and this converging tendency is stronger in higher level lesions. We showed a developing pattern of quantity (the number of mutations/mutated genes) and quality (the extent of protein structural changes) in early stages of lung adenocarcinoma, as well as a stronger converging tendency in cell proliferation and survival related pathways and functions. Altogether, this study provides a new perspective for comprehension of genomic mutational data and might shed new light on deciphering the molecular evolution of early stage lung adenocarcinoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004530","title":"HCA_Lung_Immune_Foetal_Wellcome_RNA","description":"Immune Cell Analysis in Fetal Lung \n\nWe have purified CD45+ immune cell populations from lung tissue from fetuses spanning a range of ages within first and second trimester (8-20pcw).  We are now thawing preserved cells and will carry 5’10X sequencing as well as plate-based sequencing of FACS-sorted T cells, B cells and macroghages to better understand the lung immune landscape in pregnancy.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Immune Cell Analysis in Fetal Lung \n\nWe have purified CD45+ immune cell populations from lung tissue from fetuses spanning a range of ages within first and second trimester (8-20pcw).  We are now thawing preserved cells and will carry 5’10X sequencing as well as plate-based sequencing of FACS-sorted T cells, B cells and macroghages to better understand the lung immune landscape in pregnancy.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004531","title":"CRISPR_Cas___scRNAseq_in_human_iPSCs","description":"This study will deep sequence 2 test samples from single-cell CRISPR screens, aimed to conduct the quality control of our single-cell gene expression library and guide RNA library, as well as validate our experimental approach. The samples were prepared using a method adapted from a recent publication about single-cell CRISPR screens. Single cells were collected after CRISPR screens with high viability. Single cell RNA libraries were constructed using the 10x Genomics 5'v1 kit. The guide RNAs and the transcriptome were capture simultaneously from each single cell. Therefore each sample will generate a gene expression library and a guide RNA library, which will be mixed together for seq.    \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Multiple core questions in human genetics could be addressed by measuring transcriptomes of single cells in response to various genetic perturbations. Here we propose to carry out the smallest possible pilot single-cell CRISPR screens to: 1) validate the experimental and computational approaches for pooled CRISPR screens with scRNAseq readout; 2) evaluate alternative methods of cDNA library enrichment and depletion for measuring a targeted set of transcripts; 3) establish statistical guidelines for coverage requirements of future experiments. To do so, we target 10 pluripotency maintenance genes in iPSCs cells, which are not essential for survival, using CRISPR/Cas9 knockout. We then construct single cell RNA libraries using the 10x Genomics 5'v1 kit. This also allows direct capture of guide RNAs from the 5’ end to simultaneously recover the transcriptome of each single cell, as well as the perturbation applied. Each of the 10 selected genes is targeted by 5 different guide RNAs, and our target is to sequence approximately 100 cells per guide RNA for 5,000 cells total. We also add 20 non-targeting guide RNAs, each of them targeting 50 cells, for an additional 1000 cells. This pilot screen allows us to study the effect of the knockout of a small set of pluripotency maintenance factors on the transcriptome of single cells.  And it is the beginning of a more substantial effort to establish gene regulatory networks in early differentiation, and their differences across different health donors, by studying the effect of gene knockouts on the transcriptome.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004532","title":"RNA Sequencing of paediatric patients with B lymphoblastic leukemia","description":"RNA sequencing was performed on 148 Bone marrow of peripheral blood samples of paediatric patients with B-ALL.","abstract":"RNA sequencing was performed on 148 Bone marrow of peripheral blood samples of paediatric patients with B-ALL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-06T09:19:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004533","title":"RNA-Sequencing and Somatic Mutation Status of Adrenocortical Tumors: Novel Pathogenetic Insights","description":"To investigate the relationship between transcriptome profile and genetic background in a large series of adrenocortical tumors and to identify new potential pathogenetic mechanisms, we performed  transcriptome profiling by high-throughput sequencing. We collected snap-frozen tissue from patients with adrenocortical tumors (n = 59) with known genetic background: 26 adenomas with Cushing syndrome, 17 \nadenomas with mild autonomous cortisol secretion, 9 endocrine-inactive adenomas, 7 adrenocortical carcinomas. Additionally, we sequenced 4 control samples.","abstract":"To investigate the relationship between transcriptome profile and genetic background in a large series of adrenocortical tumors and to identify new potential pathogenetic mechanisms, we performed  transcriptome profiling by high-throughput sequencing. We collected snap-frozen tissue from patients with adrenocortical tumors (n = 59) with known genetic background: 26 adenomas with Cushing syndrome, 17 \nadenomas with mild autonomous cortisol secretion, 9 endocrine-inactive adenomas, 7 adrenocortical carcinomas. Additionally, we sequenced 4 control samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-06T12:07:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004534","title":"Transcriptomic analysis of the Phase 3 COMPARZ clinical trial","description":"Metastasis remains the main reason for renal cell carcinoma (RCC)-associated mortality. Tyrosine kinase inhibitors (TKI) impart clinical benefit for most RCC patients but the determinants of response are poorly understood. We report an integrated genomic and transcriptomic analysis of metastatic clear cell RCC (ccRCC) patients treated with TKI therapy and identify predictors of response. Patients in the COMPARZ phase III trial received first-line sunitinib or pazopanib with comparable efficacy. Microarray-based transcriptomic analyses with results from Next-gen genomic analyses of targeted genes revealed distinct molecular subgroups associated with response and survival.","abstract":"Metastasis remains the main reason for renal cell carcinoma (RCC)-associated mortality. Tyrosine kinase inhibitors (TKI) impart clinical benefit for most RCC patients but the determinants of response are poorly understood. We report an integrated genomic and transcriptomic analysis of metastatic clear cell RCC (ccRCC) patients treated with TKI therapy and identify predictors of response. Patients in the COMPARZ phase III trial received first-line sunitinib or pazopanib with comparable efficacy. Microarray-based transcriptomic analyses with results from Next-gen genomic analyses of targeted genes revealed distinct molecular subgroups associated with response and survival.","study_type":"Other","pubmed_ids":[30622105,32820162],"external_links":null,"is_released":true,"released_date":"2020-07-06T15:30:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004535","title":"Whole genome sequencing for novel neuromuscular disease gene discovery","description":"This peripheral neuropathy patient underwent whole genome sequencing to find the cause of their disease. They were undiagnosed by current standard-of-care practice, which is neurogenetic panel screening. This is a paediatric case.","abstract":"This peripheral neuropathy patient underwent whole genome sequencing to find the cause of their disease. They were undiagnosed by current standard-of-care practice, which is neurogenetic panel screening. This is a paediatric case.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-07T08:29:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004536","title":"Multiomic profiling of early-passage melanoma cell lines.","description":"This study utilises multiomic profiling of early-passage melanoma cell lines to explore the interactions between distinct modalities of molecular regulation influencing melanoma cellular phenotype.","abstract":"This study utilises multiomic profiling of early-passage melanoma cell lines to explore the interactions between distinct modalities of molecular regulation influencing melanoma cellular phenotype.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-07T12:51:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004537","title":"A population specific reference genome defined from the analysis of 153 United Arab Emirates nationals.","description":null,"abstract":"The composition of the population of a country contributes to the uniqueness of each national DNA sequencing project and, ideally, individual reference genomes are required to reduce the confounding nature of ethnic bias. This work depicts a representative Whole Genome Sequencing effort of an understudied population. Specifically, the sequences from 120 whole genomes and 33 whole exomes with high coverage including their consensus sequence were used to construct the first ever population specific reference genome for the United Arab Emirates (UAERG).","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004538","title":"Memory-like HCV-specific CD8+ T cells retain a chronic scar after cure of chronic HCV infection","description":"Chronic hepatitis C virus (HCV) infection is associated with CD8+ T-cell exhaustion characterized by limited effector functions and thus compromised anti-viral activity. Exhausted HCV-specific CD8+ T cells are comprised of memory-like and terminally exhausted CD8+ T-cell subsets. So far, little is not known about the molecular profile and fate of these cells after elimination of chronic antigen stimulation by direct acting antiviral therapy (DAA). Here, we report an antigen-driven molecular core signature underlying exhausted CD8+ T-cell subset heterogeneity in chronic viral infection with a progenitor/progeny relationship of memory-like and terminally exhausted HCV-specific CD8+ T cells via an intermediate stage. Furthermore, transcriptional profiling reveals that the memory-like cells remain after DAA-mediated cure while  terminally exhausted HCV-specific CD8+ T-cell subsets are lost. Thus, the memory polarization of the overall HCV-specific CD8+ T-cell response after cure does not result from re-differentiation of exhausted T cells. Consequently, antigen elimination has little impact on the exhausted core signature of memory-like CD8+ T cells that remains clearly different from bona fide T-cell memory. These results identify a molecular signature of T-cell exhaustion that is imprinted like a chronic scar in HCV-specific CD8+ T cells even after HCV cure, highlighting the requirement of re-programming to elicit full effector potential of exhausted T cells.","abstract":"Chronic hepatitis C virus (HCV) infection is associated with CD8+ T-cell exhaustion characterized by limited effector functions and thus compromised anti-viral activity. Exhausted HCV-specific CD8+ T cells are comprised of memory-like and terminally exhausted CD8+ T-cell subsets. So far, little is not known about the molecular profile and fate of these cells after elimination of chronic antigen stimulation by direct acting antiviral therapy (DAA). Here, we report an antigen-driven molecular core signature underlying exhausted CD8+ T-cell subset heterogeneity in chronic viral infection with a progenitor/progeny relationship of memory-like and terminally exhausted HCV-specific CD8+ T cells via an intermediate stage. Furthermore, transcriptional profiling reveals that the memory-like cells remain after DAA-mediated cure while  terminally exhausted HCV-specific CD8+ T-cell subsets are lost. Thus, the memory polarization of the overall HCV-specific CD8+ T-cell response after cure does not result from re-differentiation of exhausted T cells. Consequently, antigen elimination has little impact on the exhausted core signature of memory-like CD8+ T cells that remains clearly different from bona fide T-cell memory. These results identify a molecular signature of T-cell exhaustion that is imprinted like a chronic scar in HCV-specific CD8+ T cells even after HCV cure, highlighting the requirement of re-programming to elicit full effector potential of exhausted T cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-07T13:57:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004539","title":"Clinical relevance of somatic copy-number alterations in plasma circulating tumor DNA from advanced EGFR-mutated NSCLC patients treated with osimertinib","description":"Background: Somatic copy-number alterations (SCNAs) are associated with drug resistance in patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) treated with EGFR-tyrosine kinase inhibitors (TKIs). The purpose of our study was to assess the clinical relevance and development of genome-wide SCNAs in plasma circulating tumor DNA (ctDNA) under osimertinib therapy.Methods: We included 43 patients with advanced EGFR T790M-positive lung adenocarcinoma who were treated with osimertinib after progression under previous EGFR-TKI therapy. We performed genomic profiling of ctDNA in plasma samples from each patient obtained pre-osimertinib and after patients developed resistance to osimertinib. SCNAs were detected by shallow whole-genome plasma sequencing and EGFR mutations were assessed by droplet digital PCR.Results: SCNAs in resistance-related genes (rrSCNAs) were detected in 10 out of 39 (25.6%) evaluable patients before start of osimertinib. The presence of rrSCNAs in plasma before initiation of osimertinib therapy was associated with a lower response rate to osimertinib (50% versus 86%, p=0.02) and was an independent predictor for shorter progression-free survival (adjusted HR 3.26, 95% CI 1.37-7.75, p=0.008) and overall survival (adjusted HR 2.41, 95% CI 1.09-5.34, p=0.03).Conclusions: Genomic profiling of plasma ctDNA is clinically relevant and affects the efficacy and clinical outcome of osimertinib. Our approach allows comprehensive assessment of SCNAs in plasma samples of lung adenocarcinoma patients and may help to guide genotype-specific therapeutic strategies in the future.","abstract":"Background: Somatic copy-number alterations (SCNAs) are associated with drug resistance in patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) treated with EGFR-tyrosine kinase inhibitors (TKIs). The purpose of our study was to assess the clinical relevance and development of genome-wide SCNAs in plasma circulating tumor DNA (ctDNA) under osimertinib therapy.Methods: We included 43 patients with advanced EGFR T790M-positive lung adenocarcinoma who were treated with osimertinib after progression under previous EGFR-TKI therapy. We performed genomic profiling of ctDNA in plasma samples from each patient obtained pre-osimertinib and after patients developed resistance to osimertinib. SCNAs were detected by shallow whole-genome plasma sequencing and EGFR mutations were assessed by droplet digital PCR.Results: SCNAs in resistance-related genes (rrSCNAs) were detected in 10 out of 39 (25.6%) evaluable patients before start of osimertinib. The presence of rrSCNAs in plasma before initiation of osimertinib therapy was associated with a lower response rate to osimertinib (50% versus 86%, p=0.02) and was an independent predictor for shorter progression-free survival (adjusted HR 3.26, 95% CI 1.37-7.75, p=0.008) and overall survival (adjusted HR 2.41, 95% CI 1.09-5.34, p=0.03).Conclusions: Genomic profiling of plasma ctDNA is clinically relevant and affects the efficacy and clinical outcome of osimertinib. Our approach allows comprehensive assessment of SCNAs in plasma samples of lung adenocarcinoma patients and may help to guide genotype-specific therapeutic strategies in the future.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-07T16:40:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004540","title":"Whole Genome Sequencing of 317 individuals from the Pacific region","description":"Although genetic studies of modern Oceanians have revealed varying levels of admixture with populations of East Asian ancestry, attributed to the Austronesian expansion, the early peopling history of Oceania remains poorly characterized. Additionally, it is currently unknown whether and how the settlement of the Pacific was accompanied by genetic adaptation to island environments, and if archaic introgression facilitated this process in Oceanians, who present the highest worldwide levels of combined Neanderthal and Denisovan ancestry. This study reports the first whole genome-based survey that addresses a wide range of questions related to the demographic and adaptive history of Pacific populations.","abstract":"Although genetic studies of modern Oceanians have revealed varying levels of admixture with populations of East Asian ancestry, attributed to the Austronesian expansion, the early peopling history of Oceania remains poorly characterized. Additionally, it is currently unknown whether and how the settlement of the Pacific was accompanied by genetic adaptation to island environments, and if archaic introgression facilitated this process in Oceanians, who present the highest worldwide levels of combined Neanderthal and Denisovan ancestry. This study reports the first whole genome-based survey that addresses a wide range of questions related to the demographic and adaptive history of Pacific populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-08T13:43:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004541","title":"Giant congenital nevi exome sequencing","description":"Characterization of the genomic landscape of giant congenital nevi.","abstract":"Characterization of the genomic landscape of giant congenital nevi.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-09T01:52:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004542","title":"Gene expression profiling of nasopharyngeal carcinoma","description":"We retrospectively collected 150 non-metastatic, pretreatment, formalin-fixed, paraffin-embedded (FFPE) nasopharyngeal carcinoma (NPC) samples as validation cohort 1. Also, we prospectively collected 32 FFPE samples from NPC patients enrolled in a trial evaluating anti-PD-1 antibody as validation cohort 2. Total RNA was extracted and hybridised to an Affymetrix HTA 2.0 microarray. In this study, we investigated the immune status of the tumour microenvironment (TME) based on gene expression profiles to classify NPC into biologically distinct immune subtypes, and clarify their associations with prognosis and immunotherapy response.","abstract":"We retrospectively collected 150 non-metastatic, pretreatment, formalin-fixed, paraffin-embedded (FFPE) nasopharyngeal carcinoma (NPC) samples as validation cohort 1. Also, we prospectively collected 32 FFPE samples from NPC patients enrolled in a trial evaluating anti-PD-1 antibody as validation cohort 2. Total RNA was extracted and hybridised to an Affymetrix HTA 2.0 microarray. In this study, we investigated the immune status of the tumour microenvironment (TME) based on gene expression profiles to classify NPC into biologically distinct immune subtypes, and clarify their associations with prognosis and immunotherapy response.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-09T10:04:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004543","title":"Myeloid cell-associated resistance to immune checkpoint blockade in urothelial cancer identified through bulk and single-cell RNA sequencing. CM275.","description":"Using pre-treatment tumor transcriptomic data from clinical trials exploring PD-1/PD-L1 blockade in metastatic urothelial cancer, we identified a “good immune” module associated with response and “bad immune” and stromal modules associated with resistance. We mapped these modules onto single-cell RNA sequencing data demonstrating the good immune module emanated predominantly from T, NK, and B cells, the bad immune module from monocytes/macrophages, and the stromal module from fibroblasts. Deconvolution of the bad immune module revealed a microenvironment characterized by recruitment and/or reprogramming of myeloid cells linked to an immunosuppressive milieu. These findings uncover putative biomarkers and targets to overcome PD-1/PD-L1 blockade resistance.","abstract":"Using pre-treatment tumor transcriptomic data from clinical trials exploring PD-1/PD-L1 blockade in metastatic urothelial cancer, we identified a “good immune” module associated with response and “bad immune” and stromal modules associated with resistance. We mapped these modules onto single-cell RNA sequencing data demonstrating the good immune module emanated predominantly from T, NK, and B cells, the bad immune module from monocytes/macrophages, and the stromal module from fibroblasts. Deconvolution of the bad immune module revealed a microenvironment characterized by recruitment and/or reprogramming of myeloid cells linked to an immunosuppressive milieu. These findings uncover putative biomarkers and targets to overcome PD-1/PD-L1 blockade resistance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004544","title":"MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas","description":"Temozolomide (TMZ) is an oral alkylating agent used for the treatment of glioblastoma and is now becoming a chemotherapeutic option in patients diagnosed with high-risk low-grade gliomas1. The O-6-methylguanine-DNA methyltransferase (MGMT) is responsible for the direct repair of the main TMZ-induced toxic DNA adduct, the O6-Methylguanine lesion. MGMT promoter hypermethylation is currently the only known biomarker for TMZ response in glioblastoma patients2. Here we show that a subset of recurrent gliomas carry MGMT genomic rearrangements that lead to MGMT overexpression, independently from changes in its promoter methylation. By leveraging the CRISPR/Cas9 technology we generated some of these MGMT rearrangements in glioma cells and demonstrated that they lead to TMZ resistance both in vitro and in vivo. Lastly we showed that such fusions can be detected in tumor-derived exosomes and could potentially represent an early detection marker of tumor recurrence in a subset of patients treated with TMZ.","abstract":"Temozolomide (TMZ) is an oral alkylating agent used for the treatment of glioblastoma and is now becoming a chemotherapeutic option in patients diagnosed with high-risk low-grade gliomas1. The O-6-methylguanine-DNA methyltransferase (MGMT) is responsible for the direct repair of the main TMZ-induced toxic DNA adduct, the O6-Methylguanine lesion. MGMT promoter hypermethylation is currently the only known biomarker for TMZ response in glioblastoma patients2. Here we show that a subset of recurrent gliomas carry MGMT genomic rearrangements that lead to MGMT overexpression, independently from changes in its promoter methylation. By leveraging the CRISPR/Cas9 technology we generated some of these MGMT rearrangements in glioma cells and demonstrated that they lead to TMZ resistance both in vitro and in vivo. Lastly we showed that such fusions can be detected in tumor-derived exosomes and could potentially represent an early detection marker of tumor recurrence in a subset of patients treated with TMZ.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-12T06:26:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004545","title":"Conserved interferon-gamma signaling and decreased immune exclusion programs in responses to immune checkpoint blockade therapy","description":"We analyzed baseline and on-therapy tumor biopsies from 101 patients with advanced melanoma treated with nivolumab (anti-PD-1) alone or combined with ipilimumab (anti-CTLA-4). Analysis of whole transcriptome data showed that T cell infiltration and interferon-gamma signaling signatures corresponded most highly with clinical response to therapy, with a reciprocal decrease in cell cycle and WNT signaling pathways in responding biopsies. Clinical outcome differences were likely not due to differential melanoma cell responses to interferon-gamma, as 57 human melanoma cell lines exposed in vitro to this cytokine showed a conserved interferon-gamma transcriptome response unless they had mutations that precluded signaling from the interferon-gamma receptor. Therefore, the magnitude of the antitumor T cell response and the corresponding downstream interferon-gamma signaling are the main drivers of clinical response or resistance to immune checkpoint blockade therapy.","abstract":"We analyzed baseline and on-therapy tumor biopsies from 101 patients with advanced melanoma treated with nivolumab (anti-PD-1) alone or combined with ipilimumab (anti-CTLA-4). Analysis of whole transcriptome data showed that T cell infiltration and interferon-gamma signaling signatures corresponded most highly with clinical response to therapy, with a reciprocal decrease in cell cycle and WNT signaling pathways in responding biopsies. Clinical outcome differences were likely not due to differential melanoma cell responses to interferon-gamma, as 57 human melanoma cell lines exposed in vitro to this cytokine showed a conserved interferon-gamma transcriptome response unless they had mutations that precluded signaling from the interferon-gamma receptor. Therefore, the magnitude of the antitumor T cell response and the corresponding downstream interferon-gamma signaling are the main drivers of clinical response or resistance to immune checkpoint blockade therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-12T15:55:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004546","title":"Survival Benefit and Genetic Profile of Pemetrexed as Initial Chemotherapy in Selected Chinese Patients with Advanced Lung Adenocarcinoma","description":"We retrospectively collected patients (n=1047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT (r=0.403, P&lt;0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT &gt;6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤6.9 months set. This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.","abstract":"We retrospectively collected patients (n=1047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT (r=0.403, P&lt;0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT &gt;6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤6.9 months set. This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-13T02:29:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004547","title":"MutWP4___contamination_study","description":"Genotyping required for confirmation of source of contamination. Sequencing not required (at present)","abstract":"Genotyping required for confirmation of source of contamination. Sequencing not required (at present)","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004548","title":"A Multifactorial Tumor and Immune Cell Profile Determines Response to Immune Checkpoint blockade in Melanoma","description":"The complex crosstalk between tumor and immune cells during immune checkpoint blockade mandates the development of integrated models that interpret the anti-tumor immune response and predict clinical outcome. We have integrated genome-wide sequence and structural alterations with pre and on-therapy transcriptomic and T cell repertoire features for a cohort of 64 immunotherapy-naïve melanomas treated with anti-PD1 monotherapy or combined anti-PD1 and anti-CTLA4 therapy. While tumor mutation burden (TMB) was associated with improved response to therapy, expressed mutation burden was superior to TMB in predicting outcome. An increased pre-existing T cell density differentiated responding from non-responding tumors independent of therapy. Importantly, T cell repertoire reshaping determined by T cell receptor (TCR) clonotypic regressions and expansions reflected response to therapy such that a more dynamic repertoire predicted improved clinical outcome. Through whole-transcriptome analyses, we discovered differential abundance of B cell subsets in responding tumors, which highlights the importance of the interplay between pre-existing T and B cell immunity in shaping therapeutic response. Tumor temporal trajectories during therapy revealed distinct patterns of molecular response related to expressed mutation elimination or retention that accurately interpreted clinical response. High-dimensional genomic, transcriptomic and immune repertoire data were integrated by both a machine learning and a censored regression approach, resulting in a harmonized multi-modal predictor of response to immune checkpoint blockade. B cell abundance, expressed mutation load and tumor aneuploidy were combined to identify patients at high risk for recurrence, such that high risk patients had a significantly shorter progression-free survival (HR=9.18, 95% CI: 3.14-26.85, p=3.4e-06) especially in the anti-PD1/anti-CTLA4 group (HR=20.34, 95% CI: 4.08-101.32, p=1.68e-06).","abstract":"The complex crosstalk between tumor and immune cells during immune checkpoint blockade mandates the development of integrated models that interpret the anti-tumor immune response and predict clinical outcome. We have integrated genome-wide sequence and structural alterations with pre and on-therapy transcriptomic and T cell repertoire features for a cohort of 64 immunotherapy-naïve melanomas treated with anti-PD1 monotherapy or combined anti-PD1 and anti-CTLA4 therapy. While tumor mutation burden (TMB) was associated with improved response to therapy, expressed mutation burden was superior to TMB in predicting outcome. An increased pre-existing T cell density differentiated responding from non-responding tumors independent of therapy. Importantly, T cell repertoire reshaping determined by T cell receptor (TCR) clonotypic regressions and expansions reflected response to therapy such that a more dynamic repertoire predicted improved clinical outcome. Through whole-transcriptome analyses, we discovered differential abundance of B cell subsets in responding tumors, which highlights the importance of the interplay between pre-existing T and B cell immunity in shaping therapeutic response. Tumor temporal trajectories during therapy revealed distinct patterns of molecular response related to expressed mutation elimination or retention that accurately interpreted clinical response. High-dimensional genomic, transcriptomic and immune repertoire data were integrated by both a machine learning and a censored regression approach, resulting in a harmonized multi-modal predictor of response to immune checkpoint blockade. B cell abundance, expressed mutation load and tumor aneuploidy were combined to identify patients at high risk for recurrence, such that high risk patients had a significantly shorter progression-free survival (HR=9.18, 95% CI: 3.14-26.85, p=3.4e-06) especially in the anti-PD1/anti-CTLA4 group (HR=20.34, 95% CI: 4.08-101.32, p=1.68e-06).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-13T17:08:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004549","title":"RNAseq of human primary lung adenocarcinoma and brain metastases","description":null,"abstract":"Lung cancer has the highest incidence of metastases to the brain (~40%). The median survival is only 3-6 months. In the current study, RNA sequencing of human primary lung adenocarcinoma tissue and their brain metastasis were performed.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004550","title":"Therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma","description":"Whole genome sequencing of ATRX / TP53 knockdown clones of the neuroblastoma cell line SK-N-SH","abstract":"Whole genome sequencing of ATRX / TP53 knockdown clones of the neuroblastoma cell line SK-N-SH","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-14T12:42:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004551","title":"Super enhancers define regulatory subtypes and cell identity in neuroblastoma","description":"Half of the children diagnosed with neuroblastoma have high-risk disease, disproportionately contributing to overall childhood cancer-related deaths. In addition to recurrent gene mutations, there is increasing evidence supporting the role of epigenetic deregulation in disease pathogenesis. Yet, comprehensive cis-regulatory network descriptions from neuroblastoma tissues are lacking. Here, using genome-wide H3K27ac profiles across 60 neuroblastomas, covering the different clinical and molecular subtypes, we identified four major super enhancer-driven epigenetic subtypes and their underlying master regulatory networks. Three of these subtypes recapitulated known clinical groups, namely MYCN amplified, MYCN non-amplified high-risk and MYCN non-amplified low-risk neuroblastomas. The fourth subtype, exhibiting mesenchymal characteristics, shared features with multipotent Schwann cell precursors, was induced by RAS activation and enriched in relapsed disease. Notably, CCND1, a disease essential gene, was regulated by both mesenchymal and adrenergic regulatory networks converging on distinct super-enhancer modules. Together, this reveals subtype-specific super-enhancer regulation in neuroblastoma.","abstract":"Half of the children diagnosed with neuroblastoma have high-risk disease, disproportionately contributing to overall childhood cancer-related deaths. In addition to recurrent gene mutations, there is increasing evidence supporting the role of epigenetic deregulation in disease pathogenesis. Yet, comprehensive cis-regulatory network descriptions from neuroblastoma tissues are lacking. Here, using genome-wide H3K27ac profiles across 60 neuroblastomas, covering the different clinical and molecular subtypes, we identified four major super enhancer-driven epigenetic subtypes and their underlying master regulatory networks. Three of these subtypes recapitulated known clinical groups, namely MYCN amplified, MYCN non-amplified high-risk and MYCN non-amplified low-risk neuroblastomas. The fourth subtype, exhibiting mesenchymal characteristics, shared features with multipotent Schwann cell precursors, was induced by RAS activation and enriched in relapsed disease. Notably, CCND1, a disease essential gene, was regulated by both mesenchymal and adrenergic regulatory networks converging on distinct super-enhancer modules. Together, this reveals subtype-specific super-enhancer regulation in neuroblastoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-14T14:59:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004552","title":"Super enhancers define regulatory subtypes and cell identity in neuroblastoma - RNA-seq","description":"Half of the children diagnosed with neuroblastoma have high-risk disease, disproportionately contributing to overall childhood cancer-related deaths. In addition to recurrent gene mutations, there is increasing evidence supporting the role of epigenetic deregulation in disease pathogenesis. Yet, comprehensive cis-regulatory network descriptions from neuroblastoma tissues are lacking. Here, using genome-wide H3K27ac profiles across 60 neuroblastomas, covering the different clinical and molecular subtypes, we identified four major super enhancer-driven epigenetic subtypes and their underlying master regulatory networks. Three of these subtypes recapitulated known clinical groups, namely MYCN amplified, MYCN non-amplified high-risk and MYCN non-amplified low-risk neuroblastomas. The fourth subtype, exhibiting mesenchymal characteristics, shared features with multipotent Schwann cell precursors, was induced by RAS activation and enriched in relapsed disease. Notably, CCND1, a disease essential gene, was regulated by both mesenchymal and adrenergic regulatory networks converging on distinct super-enhancer modules. Together, this reveals subtype-specific super-enhancer regulation in neuroblastoma.","abstract":"Half of the children diagnosed with neuroblastoma have high-risk disease, disproportionately contributing to overall childhood cancer-related deaths. In addition to recurrent gene mutations, there is increasing evidence supporting the role of epigenetic deregulation in disease pathogenesis. Yet, comprehensive cis-regulatory network descriptions from neuroblastoma tissues are lacking. Here, using genome-wide H3K27ac profiles across 60 neuroblastomas, covering the different clinical and molecular subtypes, we identified four major super enhancer-driven epigenetic subtypes and their underlying master regulatory networks. Three of these subtypes recapitulated known clinical groups, namely MYCN amplified, MYCN non-amplified high-risk and MYCN non-amplified low-risk neuroblastomas. The fourth subtype, exhibiting mesenchymal characteristics, shared features with multipotent Schwann cell precursors, was induced by RAS activation and enriched in relapsed disease. Notably, CCND1, a disease essential gene, was regulated by both mesenchymal and adrenergic regulatory networks converging on distinct super-enhancer modules. Together, this reveals subtype-specific super-enhancer regulation in neuroblastoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-14T15:05:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004553","title":"RNA sequencing of ductal carcinoma in situ cell lines, ETCC-006 and ETCC-010","description":null,"abstract":"This study is part of the molecular and cellular characterization of two patient-derived ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010. Using total RNA extracted from these cell lines, libraries were prepared and sequenced using the NextSeq sequencer and read 85 bases from library inserts at the Genomics Core Facility, EMBL, Heidelberg. The study is the first to provide RNAseq data for ETCC-006 and ETCC-010 DCIS cell lines.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004554","title":"Prospective high-throughput genome profiling in advanced cancers:","description":"Genomics-based tumor profiling in advanced cancers (aC) was recently demonstrated as feasible in clinical practice. After the prospective pilot PANDORA study done on advanced breast cancers, we conducted a prospective monocenter clinical trial called PERMED01 to evaluate the number patients with locally advanced or metastatic cancer for whom identification of molecular alterations in tumor samples could lead to the delivery of a targeted therapy","abstract":"Genomics-based tumor profiling in advanced cancers (aC) was recently demonstrated as feasible in clinical practice. After the prospective pilot PANDORA study done on advanced breast cancers, we conducted a prospective monocenter clinical trial called PERMED01 to evaluate the number patients with locally advanced or metastatic cancer for whom identification of molecular alterations in tumor samples could lead to the delivery of a targeted therapy","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-15T13:49:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004555","title":"Clinical Outcomes by Tumor Mutational Burden and Inflammatory Gene Expression With Combined Nivolumab and Ipilimumab or Monotherapy in Advanced Melanoma - CM67 WES","description":"Purpose\nExploratory analyses of CheckMate 066 and 067 trials were conducted to investigate associations of tumor mutational burden (TMB), a 4-gene inflammatory gene expression signature, and BRAF mutation status with tumor response, progression-free survival (PFS), and overall survival (OS) in patients with advanced melanoma.\nPatients and Methods\nPatients with known programmed death ligand 1 (PD-L1) expression and BRAF mutation status received nivolumab (NIVO) or dacarbazine in CheckMate 066 and either NIVO, ipilimumab (IPI), or NIVO+IPI in CheckMate 067. Whole exome sequencing and RNA sequencing were used to determine TMB and inflammatory gene expression signature scores, respectively. These biomarkers were evaluated in terms of their association with PFS and OS.\nResults\nIn the NIVO, NIVO+IPI, and IPI arms of CheckMate 067, longer survival was associated with high (&amp;amp;gt; median) versus low (≤ median) TMB with hazard ratios (HRs) (95% confidence interval [CI]) for PFS of 0.45 (0.30–0.65), 0.55 (0.38–0.81), and 0.60 (0.43–0.82), and for OS of 0.46 (0.30–0.71), 0.53 (0.34–0.82), and 0.52 (0.36–0.74), respectively. For NIVO-treated patients, these results were confirmed in CheckMate 066. A survival benefit was observed with high TMB and absence of BRAF mutation. Survival was associated with high versus low inflammatory signature scores with HRs (95% CI) for PFS of 0.56 (0.34–0.94), 0.40 (0.23–0.72), and 0.43 (0.27–0.70), and for OS of 0.37 (0.20–0.66), 0.38 (0.19–0.74), and 0.46 (0.27–0.79), in the NIVO, NIVO+IPI, and IPI arms, respectively. Weak correlations were observed between PD-L1, TMB, and the inflammatory signature.\nConclusions\nCombined assessment of TMB, inflammatory gene expression signature, and BRAF mutation status may be predictive for response to immunotherapy in advanced melanoma.","abstract":"Purpose\nExploratory analyses of CheckMate 066 and 067 trials were conducted to investigate associations of tumor mutational burden (TMB), a 4-gene inflammatory gene expression signature, and BRAF mutation status with tumor response, progression-free survival (PFS), and overall survival (OS) in patients with advanced melanoma.\nPatients and Methods\nPatients with known programmed death ligand 1 (PD-L1) expression and BRAF mutation status received nivolumab (NIVO) or dacarbazine in CheckMate 066 and either NIVO, ipilimumab (IPI), or NIVO+IPI in CheckMate 067. Whole exome sequencing and RNA sequencing were used to determine TMB and inflammatory gene expression signature scores, respectively. These biomarkers were evaluated in terms of their association with PFS and OS.\nResults\nIn the NIVO, NIVO+IPI, and IPI arms of CheckMate 067, longer survival was associated with high (&amp;amp;gt; median) versus low (≤ median) TMB with hazard ratios (HRs) (95% confidence interval [CI]) for PFS of 0.45 (0.30–0.65), 0.55 (0.38–0.81), and 0.60 (0.43–0.82), and for OS of 0.46 (0.30–0.71), 0.53 (0.34–0.82), and 0.52 (0.36–0.74), respectively. For NIVO-treated patients, these results were confirmed in CheckMate 066. A survival benefit was observed with high TMB and absence of BRAF mutation. Survival was associated with high versus low inflammatory signature scores with HRs (95% CI) for PFS of 0.56 (0.34–0.94), 0.40 (0.23–0.72), and 0.43 (0.27–0.70), and for OS of 0.37 (0.20–0.66), 0.38 (0.19–0.74), and 0.46 (0.27–0.79), in the NIVO, NIVO+IPI, and IPI arms, respectively. Weak correlations were observed between PD-L1, TMB, and the inflammatory signature.\nConclusions\nCombined assessment of TMB, inflammatory gene expression signature, and BRAF mutation status may be predictive for response to immunotherapy in advanced melanoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-16T05:53:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004556","title":"Novel mutations in TOP2A in gliomas","description":"High grade gliomas (HGGs) are aggressive, primary brain tumors with poor clinical outcomes. To better understand glioma pathobiology and find potential therapeutic susceptibilities, we designed a custom- panel 664 cancer- and epigenetics-related genes and employed targeted next generation sequencing to study the genomic landscape of somatic and germline variants in 182 glioma samples of different malignancy grades. Besides known  alterations in TP53, IDH1, ATRX, EGFR genes, we found several novel variants that can be potential drivers in gliomas. In four patients from the Polish glioma cohort, we identified a novel recurrent mutation in the TOP2A gene coding for Topoisomerase 2A in glioblastomas (GBM, WHO grade IV gliomas). The mutation results in a substitution of glutamic acid (E) 948 to glutamine (Q) of TOP2 A and we predicted this E948Q substitution may affect DNA binding and a TOP2A enzymatic activity.","abstract":"High grade gliomas (HGGs) are aggressive, primary brain tumors with poor clinical outcomes. To better understand glioma pathobiology and find potential therapeutic susceptibilities, we designed a custom- panel 664 cancer- and epigenetics-related genes and employed targeted next generation sequencing to study the genomic landscape of somatic and germline variants in 182 glioma samples of different malignancy grades. Besides known  alterations in TP53, IDH1, ATRX, EGFR genes, we found several novel variants that can be potential drivers in gliomas. In four patients from the Polish glioma cohort, we identified a novel recurrent mutation in the TOP2A gene coding for Topoisomerase 2A in glioblastomas (GBM, WHO grade IV gliomas). The mutation results in a substitution of glutamic acid (E) 948 to glutamine (Q) of TOP2 A and we predicted this E948Q substitution may affect DNA binding and a TOP2A enzymatic activity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-20T14:57:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004557","title":"The Genomic Landscape of Prostate Cancer Brain Metastases","description":null,"abstract":"Lethal prostate cancer commonly metastasizes to bone, lymph nodes, and visceral organs but with more effective therapies, there is an increased frequency of metastases to the brain.  Little is known about the genomic drivers of prostate cancer brain metastases (PCBM).  To address this, we conducted a comprehensive multi-regional, genomic, and targeted transcriptomic analysis of PCBM from 28 patients. We compared whole-exome and targeted RNA sequencing with matched primary tumors when available (n = 10) and with publicly available genomic data from non-brain prostate cancer metastases (n = 416). In addition to common alterations in TP53, AR, RB1, and PTEN, we identified highly significant enrichment of mutations in NF1 (25% cases (6/28), q = 0.049, 95% CI = 2.38 – 26.52, OR = 8.37) and RICTOR (17.9% cases (5/28), q = 0.01, 95% CI = 6.74 – 480.15, OR = 43.7) in PCBM compared to non-brain prostate cancer metastases, suggesting possible activation of the druggable pathways RAS/RAF/MEK/ERK and PI3K/AKT/mTOR, respectively. Compared to non-brain prostate cancer metastases, PCBM were almost three times as likely to harbor DNA homologous repair (HR) alterations (42.9% cases (12/28), p =0.016, 95% CI = 1.17 – 6.64, OR = 2.8). When considering the combination of somatic mutations, copy number alteration, and Large-scale State Transitions, 64.3% of patients (18/28) were affected.  HR alterations may be critical drivers of brain metastasis that potentially provide cancer cells a survival advantage during re-establishment in a special microenvironment.  We demonstrate that PCBM have genomic dependencies that may be exploitable through clinical interventions including PARP inhibition.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-20T17:44:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004558","title":"Deep MRD profiling defines outcome and unveils different modes of treatment resistance in standard and high risk myeloma","description":null,"abstract":"Patients with multiple myeloma (MM) carrying high risk cytogenetic abnormalities (CA) have inferior outcome despite achieving similar complete response (CR) rates when compared to cases with standard risk CA. This questions the legitimacy of CR as treatment endpoint for high risk MM, and represents a biological conundrum regarding the nature of tumor reservoirs persisting after therapy in patients with standard and high risk CA. Here, we used next-generation flow (NGF) to evaluate measurable residual disease (MRD) in MM patients with standard (N=300) vs high risk CA (N=90) enrolled in the PETHEMA/GEM2012MENOS65 trial (NCT01916252), and to identify mechanisms determining MRD resistance in both patient subgroups (N=40). The 36-month progression-free and overall survival rates were higher than 90% in patients with undetectable MRD, with no significant differences (P≥.202) between cases having standard vs high risk CA. Persistent MRD resulted in median progression-free survival of approximately three and two years in patients with standard and high risk CA, respectively (P&amp;lt;.001). Further use of NGF to isolate MRD followed by whole-exome sequencing of paired diagnostic and MRD tumor cells, revealed greater clonal selection in patients with standard risk CA, higher genomic instability with acquisition of new mutations in high risk MM, and no unifying lost or acquired genetic abnormalities driving MRD resistance. Conversely, RNA sequencing of diagnostic and MRD tumor cells uncovered the selection of MRD clones with singular transcriptional programs and ROS-mediated MRD resistance in high risk MM. Our study supports undetectable MRD as treatment endpoint for MM patients with high risk CA and proposes characterizing MRD clones to understand and overcome MRD resistance.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-21T08:29:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004559","title":"Profiling Genome-Wide DNA Methylation Patterns in Human Aortic and Mitral Valves","description":null,"abstract":"Cardiac valve structure and function are complex and include dynamic interactions between cells, extracellular matrix (ECM) and their hemodynamic environment. Valvular gene expression is tightly regulated by a variety of mechanisms including epigenetic factors such as histone modifications, RNA-based mechanisms and DNA methylation. To date, methylation fingerprints of non-diseased human aortic and mitral valves have not been studied. In this work we analyzed the differential methylation profiles of 12 non-diseased aortic and mitral valve tissue samples (in matched pairs). Analysis of methylation data (reduced representation bisulfite sequencing (RRBS)) of 1601 promoters genome-wide revealed 584 differentially methylated (DM) promoters, of which 13 were reported in endothelial mesenchymal trans-differentiation (EMT), 37 in aortic and mitral valve disease and 7 in ECM remodeling. Both functional classification as well as network analysis showed that the genes associated with the DM promoters were enriched for WNT-, Cadherin-, Endothelin-, PDGF- and VEGF- signaling implicated in valvular physiology and pathophysiology. Additional enrichment was detected for TGFB-, NOTCH- and Integrin- signaling involved in EMT as well as ECM remodeling. This data provides the first insight into differential regulation of human aortic and mitral valve tissue and identifies candidate genes linked to DM promoters. Our work will improve the understanding of valve biology, valve tissue engineering approaches and contributes to the identification of relevant drug targets.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-21T08:31:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004560","title":"IBD_Whole_Exome_Sequencing_","description":"Whole exome sequencing of patients with Inflammatory Bowel Disease","abstract":"In this study we will undertake whole-exome sequencing of UK IBD cases, this data will be combined with that from approximately 7,000 IBD cases we have already whole-genome sequenced and 12,854 sequenced in 2019 and HGI are currently undertaking the calling together with UKBB WES data as controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004561","title":"Cell types of the human retina and its organoids at single-cell resolution. Cowan et al","description":"Human organoids recapitulating the cell-type diversity and function of their target organ are valuable for basic and translational research. We developed light-sensitive human retinal organoids with multiple nuclear and synaptic layers, and functional synapses. We sequenced the RNA of 285,441 single cells from these organoids at seven developmental time points and from the periphery, fovea, pigment epithelium and choroid of light-responsive adult human retinas.","abstract":"Human organoids recapitulating the cell-type diversity and function of their target organ are valuable for basic and translational research. We developed light-sensitive human retinal organoids with multiple nuclear and synaptic layers, and functional synapses. We sequenced the RNA of 285,441 single cells from these organoids at seven developmental time points and from the periphery, fovea, pigment epithelium and choroid of light-responsive adult human retinas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-21T09:46:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004562","title":"RNASeq of PDX and CDX tumours treated with ADC","description":"Enapotamab vedotin (EnaV), an antibody-drug conjugate (ADC) targeting AXL, effectively targets tumors that display insensitivity to immunotherapy and/or tumor-specific T cells in several melanoma and lung cancer models. Mechanistically, EnaV treatment induced an inflammatory response and immunogenic cell death in tumor cells, and promoted induction of a memory-like phenotype in cytotoxic T cells. Combining EnaV with tumor-specific T cells proved superior to any treatment alone in models of melanoma and lung cancer, and increased ICB benefit in models otherwise insensitive to anti-PD-1 treatment.","abstract":"Enapotamab vedotin (EnaV), an antibody-drug conjugate (ADC) targeting AXL, effectively targets tumors that display insensitivity to immunotherapy and/or tumor-specific T cells in several melanoma and lung cancer models. Mechanistically, EnaV treatment induced an inflammatory response and immunogenic cell death in tumor cells, and promoted induction of a memory-like phenotype in cytotoxic T cells. Combining EnaV with tumor-specific T cells proved superior to any treatment alone in models of melanoma and lung cancer, and increased ICB benefit in models otherwise insensitive to anti-PD-1 treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-21T11:18:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004563","title":"Molecular_Factors_that_Drive_Colorectal_Cancer_Outcome__Church____WES_","description":"Colorectal (bowel) cancer is one of the most common cancers in the world, with over 40,000 cases each year in the UK. Most cases are cured by surgery, either alone or followed by chemotherapy (anti-cancer drug treatment). However, our inability to identify which patients require chemotherapy after surgery means that most patients receive such toxic treatment unnecessarily. Furthermore, an appreciable fraction of patients who get chemotherapy after surgery still suffer cancer recurrence, indicating that better treatments are required. By studying the molecular factors which determine cancer outcome and treatment response, we hope to identify subgroups that may require less treatment, or novel treatment targeting specific molecular vulnerabilities. Our ultimate aim is to increase cures for patients, while at the same time reducing unnecessary treatment.”","abstract":"Colorectal (bowel) cancer is one of the most common cancers in the world, with over 40,000 cases each year in the UK. Most cases are cured by surgery, either alone or followed by chemotherapy (anti-cancer drug treatment). However, our inability to identify which patients require chemotherapy after surgery means that most patients receive such toxic treatment unnecessarily. Furthermore, an appreciable fraction of patients who get chemotherapy after surgery still suffer cancer recurrence, indicating that better treatments are required. By studying the molecular factors which determine cancer outcome and treatment response, we hope to identify subgroups that may require less treatment, or novel treatment targeting specific molecular vulnerabilities. Our ultimate aim is to increase cures for patients, while at the same time reducing unnecessary treatment.”","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004564","title":"Clinical Outcomes by Tumor Mutational Burden and Inflammatory Gene Expression With Combined Nivolumab and Ipilimumab or Monotherapy in Advanced Melanoma","description":"Purpose\nExploratory analyses of CheckMate 066 and 067 trials were conducted to investigate associations of tumor mutational burden (TMB), a 4-gene inflammatory gene expression signature, and BRAF mutation status with tumor response, progression-free survival (PFS), and overall survival (OS) in patients with advanced melanoma.\nPatients and Methods\nPatients with known programmed death ligand 1 (PD-L1) expression and BRAF mutation status received nivolumab (NIVO) or dacarbazine in CheckMate 066 and either NIVO, ipilimumab (IPI), or NIVO+IPI in CheckMate 067. Whole exome sequencing and RNA sequencing were used to determine TMB and inflammatory gene expression signature scores, respectively. These biomarkers were evaluated in terms of their association with PFS and OS.\nResults\nIn the NIVO, NIVO+IPI, and IPI arms of CheckMate 067, longer survival was associated with high (&gt; median) versus low (≤ median) TMB with hazard ratios (HRs) (95% confidence interval [CI]) for PFS of 0.45 (0.30–0.65), 0.55 (0.38–0.81), and 0.60 (0.43–0.82), and for OS of 0.46 (0.30–0.71), 0.53 (0.34–0.82), and 0.52 (0.36–0.74), respectively. For NIVO-treated patients, these results were confirmed in CheckMate 066. A survival benefit was observed with high TMB and absence of BRAF mutation. Survival was associated with high versus low inflammatory signature scores with HRs (95% CI) for PFS of 0.56 (0.34–0.94), 0.40 (0.23–0.72), and 0.43 (0.27–0.70), and for OS of 0.37 (0.20–0.66), 0.38 (0.19–0.74), and 0.46 (0.27–0.79), in the NIVO, NIVO+IPI, and IPI arms, respectively. Weak correlations were observed between PD-L1, TMB, and the inflammatory signature.\nConclusions\nCombined assessment of TMB, inflammatory gene expression signature, and BRAF mutation status may be predictive for response to immunotherapy in advanced melanoma.","abstract":"Purpose\nExploratory analyses of CheckMate 066 and 067 trials were conducted to investigate associations of tumor mutational burden (TMB), a 4-gene inflammatory gene expression signature, and BRAF mutation status with tumor response, progression-free survival (PFS), and overall survival (OS) in patients with advanced melanoma.\nPatients and Methods\nPatients with known programmed death ligand 1 (PD-L1) expression and BRAF mutation status received nivolumab (NIVO) or dacarbazine in CheckMate 066 and either NIVO, ipilimumab (IPI), or NIVO+IPI in CheckMate 067. Whole exome sequencing and RNA sequencing were used to determine TMB and inflammatory gene expression signature scores, respectively. These biomarkers were evaluated in terms of their association with PFS and OS.\nResults\nIn the NIVO, NIVO+IPI, and IPI arms of CheckMate 067, longer survival was associated with high (&gt; median) versus low (≤ median) TMB with hazard ratios (HRs) (95% confidence interval [CI]) for PFS of 0.45 (0.30–0.65), 0.55 (0.38–0.81), and 0.60 (0.43–0.82), and for OS of 0.46 (0.30–0.71), 0.53 (0.34–0.82), and 0.52 (0.36–0.74), respectively. For NIVO-treated patients, these results were confirmed in CheckMate 066. A survival benefit was observed with high TMB and absence of BRAF mutation. Survival was associated with high versus low inflammatory signature scores with HRs (95% CI) for PFS of 0.56 (0.34–0.94), 0.40 (0.23–0.72), and 0.43 (0.27–0.70), and for OS of 0.37 (0.20–0.66), 0.38 (0.19–0.74), and 0.46 (0.27–0.79), in the NIVO, NIVO+IPI, and IPI arms, respectively. Weak correlations were observed between PD-L1, TMB, and the inflammatory signature.\nConclusions\nCombined assessment of TMB, inflammatory gene expression signature, and BRAF mutation status may be predictive for response to immunotherapy in advanced melanoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-22T04:15:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004565","title":"HCA_Adrenal_Foetal_WSSS_managed_access","description":"Cell Atlas of human foetal Adrenal gland\n\nThe Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess human development. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs).\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Cell Atlas of human foetal Adrenal gland\n\nThe Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess human development. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs).\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004566","title":"HCA_Heart_Disease_BHF_DZHK_RNA_","description":"Cell Atlas of the diseased human heart. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The aim of this project is to profile diseased human hearts on a single-cell level. Cardiac human tissue will be sampled from adult donors with cardiomyopathies and will be processed for 10X single cell and single nuclei RNA sequencing and spatial transcriptomics.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-22T12:34:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004567","title":"Clinical Outcomes by Tumor Mutational Burden and Inflammatory Gene Expression With Combined Nivolumab and Ipilimumab or Monotherapy in Advanced Melanoma - CM066-WES","description":"Purpose\nExploratory analyses of CheckMate 066 and 067 trials were conducted to investigate associations of tumor mutational burden (TMB), a 4-gene inflammatory gene expression signature, and BRAF mutation status with tumor response, progression-free survival (PFS), and overall survival (OS) in patients with advanced melanoma.\nPatients and Methods\nPatients with known programmed death ligand 1 (PD-L1) expression and BRAF mutation status received nivolumab (NIVO) or dacarbazine in CheckMate 066 and either NIVO, ipilimumab (IPI), or NIVO+IPI in CheckMate 067. Whole exome sequencing and RNA sequencing were used to determine TMB and inflammatory gene expression signature scores, respectively. These biomarkers were evaluated in terms of their association with PFS and OS.\nResults\nIn the NIVO, NIVO+IPI, and IPI arms of CheckMate 067, longer survival was associated with high (&gt; median) versus low (≤ median) TMB with hazard ratios (HRs) (95% confidence interval [CI]) for PFS of 0.45 (0.30–0.65), 0.55 (0.38–0.81), and 0.60 (0.43–0.82), and for OS of 0.46 (0.30–0.71), 0.53 (0.34–0.82), and 0.52 (0.36–0.74), respectively. For NIVO-treated patients, these results were confirmed in CheckMate 066. A survival benefit was observed with high TMB and absence of BRAF mutation. Survival was associated with high versus low inflammatory signature scores with HRs (95% CI) for PFS of 0.56 (0.34–0.94), 0.40 (0.23–0.72), and 0.43 (0.27–0.70), and for OS of 0.37 (0.20–0.66), 0.38 (0.19–0.74), and 0.46 (0.27–0.79), in the NIVO, NIVO+IPI, and IPI arms, respectively. Weak correlations were observed between PD-L1, TMB, and the inflammatory signature.\nConclusions\nCombined assessment of TMB, inflammatory gene expression signature, and BRAF mutation status may be predictive for response to immunotherapy in advanced melanoma.","abstract":"Purpose\nExploratory analyses of CheckMate 066 and 067 trials were conducted to investigate associations of tumor mutational burden (TMB), a 4-gene inflammatory gene expression signature, and BRAF mutation status with tumor response, progression-free survival (PFS), and overall survival (OS) in patients with advanced melanoma.\nPatients and Methods\nPatients with known programmed death ligand 1 (PD-L1) expression and BRAF mutation status received nivolumab (NIVO) or dacarbazine in CheckMate 066 and either NIVO, ipilimumab (IPI), or NIVO+IPI in CheckMate 067. Whole exome sequencing and RNA sequencing were used to determine TMB and inflammatory gene expression signature scores, respectively. These biomarkers were evaluated in terms of their association with PFS and OS.\nResults\nIn the NIVO, NIVO+IPI, and IPI arms of CheckMate 067, longer survival was associated with high (&gt; median) versus low (≤ median) TMB with hazard ratios (HRs) (95% confidence interval [CI]) for PFS of 0.45 (0.30–0.65), 0.55 (0.38–0.81), and 0.60 (0.43–0.82), and for OS of 0.46 (0.30–0.71), 0.53 (0.34–0.82), and 0.52 (0.36–0.74), respectively. For NIVO-treated patients, these results were confirmed in CheckMate 066. A survival benefit was observed with high TMB and absence of BRAF mutation. Survival was associated with high versus low inflammatory signature scores with HRs (95% CI) for PFS of 0.56 (0.34–0.94), 0.40 (0.23–0.72), and 0.43 (0.27–0.70), and for OS of 0.37 (0.20–0.66), 0.38 (0.19–0.74), and 0.46 (0.27–0.79), in the NIVO, NIVO+IPI, and IPI arms, respectively. Weak correlations were observed between PD-L1, TMB, and the inflammatory signature.\nConclusions\nCombined assessment of TMB, inflammatory gene expression signature, and BRAF mutation status may be predictive for response to immunotherapy in advanced melanoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-23T02:40:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004568","title":"Evolutionary trajectories and clonal migration underlying tumor progression and lymph node metastasis in early stage lung cancer","description":null,"abstract":"Evolutionary features and molecular determinants for tumor progression and metastasis in early stage lung cancer remain elusive. In this prospective study, targeted deep sequencing was performed on a total of 164 primary tumor regions, 112 lymph node metastases, 127 preoperative plasma samples from 127 patients with stage I-III lung cancer, LuCaTH. Progressive evolution at clonal divergence scale was observed while specific driver events were positively selected for clonal sweeps during tumor development. Recurrent evolutionary trajectories were identified which reflected distinct clinicopathological phenotypes and disease outcome. By analyzing clonal lineages and migration routes across multiple lymph mode stations, we unraveled divergent modes of clonal spread and underlying clonal seeding that determined migration capacity. Importance of multi-region and multi-tumor sequencing in therapeutics management and application of ctDNA as a prognostic marker in molecular diagnosis were evaluated. Our results depicted the progression and regional metastasis of lung cancer quantitatively and highlighted the clinical significance of including evolutionary and genomic features in the treatment planning and/or prognosis prediction.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004569","title":"Whole_Exome_Sequencing_in_non_syndromic_congenital_heart_patients_and_families_II","description":"Whole Genome Sequencing of Non-syndromic cases of congenital heart defects (CHD)\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Non-syndromic cases of congenital heart defects (CHD) exhibit variable modes of inheritance (Mendelian and non-Mendelian). Several studies using whole exome sequencing (WES) have identified strong candidates in humans. We have conducted a number of studies with collaborators and colleagues to help us understand the diverse genetic architecture of syndromic as well as non-syndromic cases and this has allowed us to clarify further the best approach for the next generation of studies. We will Whole Genome Sequence ~125 samples in collaboration with our international partner to extend our existing cohort, which will allow us to establish strong genotype-phenotype correlation as well as characterize und sub classify the observed complex genetic architecture among patients and families.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004570","title":"BELOB: Ribo-minus RNA-seq data corresponding to 96x GBM samples from the BELOB trial.","description":"Ribo-minus RNA-seq data corresponding to 96x GBM samples from the BELOB trial.","abstract":"Ribo-minus RNA-seq data corresponding to 96x GBM samples from the BELOB trial.","study_type":"Other","pubmed_ids":[26762204,34608482],"external_links":null,"is_released":true,"released_date":"2020-07-23T15:10:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004571","title":"ScRNA-seq of PBMC and whole blood samples reveals a dysregulated myeloid cell compartment in severe COVID-19","description":"In a dual-center, two-cohort study, we performed single-cell RNA-sequencing of whole blood and peripheral blood mononuclear cells to determine changes in immune cell composition and activation in mild vs. severe COVID-19 over time. This study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.","abstract":"In a dual-center, two-cohort study, we performed single-cell RNA-sequencing of whole blood and peripheral blood mononuclear cells to determine changes in immune cell composition and activation in mild vs. severe COVID-19 over time. This study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-24T09:32:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004572","title":"Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk paediatric cancer","description":"Zero Childhood Cancer is a precision medicine program to benefit children with poor-outcome, rare, relapsed or refractory cancer. Utilising tumour and germline whole genome sequencing (WGS) and RNA sequencing (RNAseq) across 252 tumours from high-risk paediatric cancer patients, we identified 968 reportable molecular aberrations (39.9% in WGS and RNAseq, 35.1% WGS-only, 25.0% RNAseq-only). 93.7% of patients had at least one germline or somatic aberration, 71.4% had therapeutic targets and 5.2% had a change in diagnosis. WGS identified pathogenic cancer-predisposing variants in 16.2% of patients. In 76 CNS tumours, methylome analysis confirmed diagnosis in 71.1% and contributed to a change of diagnosis in two cases (2.6%). To date 43 patients have received a recommended therapy, 38 of whom could be evaluated. A small but encouraging proportion of 31% showed some evidence of clinical benefit. Comprehensive molecular profiling resolved the molecular basis of virtually all high-risk cancers, which in some cases has significant clinical impact.","abstract":"Zero Childhood Cancer is a precision medicine program to benefit children with poor-outcome, rare, relapsed or refractory cancer. Utilising tumour and germline whole genome sequencing (WGS) and RNA sequencing (RNAseq) across 252 tumours from high-risk paediatric cancer patients, we identified 968 reportable molecular aberrations (39.9% in WGS and RNAseq, 35.1% WGS-only, 25.0% RNAseq-only). 93.7% of patients had at least one germline or somatic aberration, 71.4% had therapeutic targets and 5.2% had a change in diagnosis. WGS identified pathogenic cancer-predisposing variants in 16.2% of patients. In 76 CNS tumours, methylome analysis confirmed diagnosis in 71.1% and contributed to a change of diagnosis in two cases (2.6%). To date 43 patients have received a recommended therapy, 38 of whom could be evaluated. A small but encouraging proportion of 31% showed some evidence of clinical benefit. Comprehensive molecular profiling resolved the molecular basis of virtually all high-risk cancers, which in some cases has significant clinical impact.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-24T14:47:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004573","title":"Evolutionary Dynamics of Non-Coding Regions in Pancreatic Ductal Adenocarcinoma","description":"Despite the wealth of data pertaining to the biology and genetics of pancreatic ductal adenocarcinoma (PDAC), this solid tumor remains one of the most lethal tumor types. Large scale whole exome sequencing studies have revealed the recurrent genomic features of PDAC that target a defined number of core pathways.  High frequency driver gene mutations in PDAC include KRAS, TP53, CDKN2A, SMAD4 which play a major role in clonal expansions during pancreatic carcinogenesis and influence metastatic propensity. Emerging data indicate the noncoding genome also plays a role in cancer. In PDAC, few studies have focused specifically on enhancer mutations. While the non-coding genome appears to play a role, the dynamic nature of noncoding alterations with respect to clonal progression of solid tumors remains unexplored.  To address this gap in knowledge we performed multi-regional whole genome sequencing and clonal analysis to elucidate the evolutionary dynamics of non-coding regions in PDAC relative to those of the coding genome.","abstract":"Despite the wealth of data pertaining to the biology and genetics of pancreatic ductal adenocarcinoma (PDAC), this solid tumor remains one of the most lethal tumor types. Large scale whole exome sequencing studies have revealed the recurrent genomic features of PDAC that target a defined number of core pathways.  High frequency driver gene mutations in PDAC include KRAS, TP53, CDKN2A, SMAD4 which play a major role in clonal expansions during pancreatic carcinogenesis and influence metastatic propensity. Emerging data indicate the noncoding genome also plays a role in cancer. In PDAC, few studies have focused specifically on enhancer mutations. While the non-coding genome appears to play a role, the dynamic nature of noncoding alterations with respect to clonal progression of solid tumors remains unexplored.  To address this gap in knowledge we performed multi-regional whole genome sequencing and clonal analysis to elucidate the evolutionary dynamics of non-coding regions in PDAC relative to those of the coding genome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004574","title":"Measurable residual disease in elderly acute myeloid leukemia: results from the PETHEMA-FLUGAZA phase III clinical trial","description":"The value of measurable residual disease (MRD) in elderly patients with acute myeloid leukemia (AML) is inconsistent between those treated with intensive vs hypomethylating drugs, and unknown after semi-intensive therapy. We investigated the role of MRD in refining complete remission (CR) and treatment duration in the phase III PETHEMA-FLUGAZA clinical trial, that randomized 283 elderly AML patients to induction and consolidation with fludarabine plus cytarabine or induction and consolidation with 5-azacitidine. After consolidation, patients continued treatment if MRD≥0.01% or stopped if MRD&lt;0.01%, assessed by multidimensional flow cytometry (MFC). On multivariate analysis including genetic risk and treatment arm, MRD status in patients achieving CR (N=72) was the only independent prognostic factor for cumulative-incidence of relapse (HR:2.95;P=.002) and relapse-free survival (HR:3.45;P=.002). A trend for longer overall survival was observed in patients with undetectable MRD (N=13/72). Although leukemic cells from most elderly AML patients display phenotypic aberrancies vs their normal counterpart (N=258/265), CD34 progenitors from cases with undetectable MRD by MFC displayed extensive genetic abnormalities identified by whole-exome sequencing. This study supports MRD assessment to refine CR after semi-intensive therapy or hypomethylating agents, but unveils that improved sensitivity is warranted to individualize treatment and prolong survival of elderly AML patients achieving undetectable MRD.","abstract":"The value of measurable residual disease (MRD) in elderly patients with acute myeloid leukemia (AML) is inconsistent between those treated with intensive vs hypomethylating drugs, and unknown after semi-intensive therapy. We investigated the role of MRD in refining complete remission (CR) and treatment duration in the phase III PETHEMA-FLUGAZA clinical trial, that randomized 283 elderly AML patients to induction and consolidation with fludarabine plus cytarabine or induction and consolidation with 5-azacitidine. After consolidation, patients continued treatment if MRD≥0.01% or stopped if MRD&lt;0.01%, assessed by multidimensional flow cytometry (MFC). On multivariate analysis including genetic risk and treatment arm, MRD status in patients achieving CR (N=72) was the only independent prognostic factor for cumulative-incidence of relapse (HR:2.95;P=.002) and relapse-free survival (HR:3.45;P=.002). A trend for longer overall survival was observed in patients with undetectable MRD (N=13/72). Although leukemic cells from most elderly AML patients display phenotypic aberrancies vs their normal counterpart (N=258/265), CD34 progenitors from cases with undetectable MRD by MFC displayed extensive genetic abnormalities identified by whole-exome sequencing. This study supports MRD assessment to refine CR after semi-intensive therapy or hypomethylating agents, but unveils that improved sensitivity is warranted to individualize treatment and prolong survival of elderly AML patients achieving undetectable MRD.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-24T17:37:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004575","title":"Exome and transcriptome sequencing of Desmoplastic Small Round Cell Sarcoma","description":"To conduct exome and transcriptome profiling to identify secondary recurrent mutations, multi-site phylogenetic analyse and immune characterization of Desmoplastic Small Round Cell Sarcoma.","abstract":"To conduct exome and transcriptome profiling to identify secondary recurrent mutations, multi-site phylogenetic analyse and immune characterization of Desmoplastic Small Round Cell Sarcoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-26T13:50:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004576","title":"Single cell RNA sequencing of CD19 CAR T-cell infusion products","description":"We performed single cell RNA sequencing of remnants from CD19 CAR T-cell infusion products used for standard of care treatment for relapsed/refractory large B-cell lymphoma. Libraries were prepared using 10X 5’ GEX chemistry and sequenced on an Illumina HiSeq 4000 to obtain &gt;50,000 reads per cell.","abstract":"We performed single cell RNA sequencing of remnants from CD19 CAR T-cell infusion products used for standard of care treatment for relapsed/refractory large B-cell lymphoma. Libraries were prepared using 10X 5’ GEX chemistry and sequenced on an Illumina HiSeq 4000 to obtain &gt;50,000 reads per cell.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-26T21:23:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004577","title":"ky249","description":"KY249","abstract":"KY249","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004578","title":"Exome sequencing of paired primary tumor and metastatic breast cancer","description":"Prognosis evaluation of advanced breast cancer and therapeutic strategy are mostly based on clinical features of advanced disease and molecular profiling of the primary tumor.\nVery few studies have evaluated the impact of a prospective documentation of metastatic subtyping.\nThe genomic landscape of metastatic breast cancer has mostly been described in very advanced, pretreated disease, limiting its transferability to clinical use.","abstract":"Prognosis evaluation of advanced breast cancer and therapeutic strategy are mostly based on clinical features of advanced disease and molecular profiling of the primary tumor.\nVery few studies have evaluated the impact of a prospective documentation of metastatic subtyping.\nThe genomic landscape of metastatic breast cancer has mostly been described in very advanced, pretreated disease, limiting its transferability to clinical use.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-28T14:02:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004579","title":"HSC_population_dynamics___KX004_PB_SPL_samples","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004580","title":"HSC_population_dynamics___KX009_samples","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-29T10:58:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004581","title":"HSC_population_dynamics___KX010_samples","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-29T11:06:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004582","title":"TransNEO neoadjuvant breast cancer study","description":null,"abstract":"Whole exome, shallow whole genome, and RNA-sequencing data from a cohort of 168 women with breast cancer receiving neoadjuvant chemotherapy.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-29T10:24:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004583","title":"Hydroxycarbamide effect on DNA methylation and gene expression in MPN patients","description":"Hydroxycarbamide (HC), is a cytoreductive drug frequently used to control cell blood counts in patients with myeloproliferative neoplasms (MPNs).To further explore the effects of HC in MPN patients, we performed DNA methylation and gene expression profiling of two differentially developed and clinically relevant cell types, both before and following HC exposure.","abstract":"Hydroxycarbamide (HC), is a cytoreductive drug frequently used to control cell blood counts in patients with myeloproliferative neoplasms (MPNs).To further explore the effects of HC in MPN patients, we performed DNA methylation and gene expression profiling of two differentially developed and clinically relevant cell types, both before and following HC exposure.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-29T10:58:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004584","title":"Functional screening on patient-derived organoids identifies a therapeutic bispecific antibody that triggers EGFR degradation in LGR5+ tumor cells","description":"Patient-derived organoids (PDOs) have demonstrated predictive value in prospective clinical trials supporting selection of personalized treatments. Because PDOs retain the organization and physiological functions of their source tissue, PDO biobanks could also be an ideal substrate to screen for novel therapeutic interventions. \nHere we describe a large-scale functional screen of dual targeting bispecific antibodies (bAbs) on a colorectal cancer (CRC) PDO biobank to target their dependency on cancer stem cells.\nA novel drug discovery pipeline was assembled where therapeutic bAb panels generated against WNT and receptor tyrosine kinases (RTK) targets were functionally evaluated by high content imaging to capture the complexity of PDO responses across a wide range of different CRCs and paired normal colonic mucosa samples. Our strategy resulted in a bAb that specifically triggers EGFR degradation in LGR5+ CSCs and that exhibits unique therapeutic properties such as potent growth inhibition of KRAS mutant CRCs, blockade of metastasis initiation in preclinical models and minimal toxicity towards normal LGR5+ colon stem cells.","abstract":"Patient-derived organoids (PDOs) have demonstrated predictive value in prospective clinical trials supporting selection of personalized treatments. Because PDOs retain the organization and physiological functions of their source tissue, PDO biobanks could also be an ideal substrate to screen for novel therapeutic interventions. \nHere we describe a large-scale functional screen of dual targeting bispecific antibodies (bAbs) on a colorectal cancer (CRC) PDO biobank to target their dependency on cancer stem cells.\nA novel drug discovery pipeline was assembled where therapeutic bAb panels generated against WNT and receptor tyrosine kinases (RTK) targets were functionally evaluated by high content imaging to capture the complexity of PDO responses across a wide range of different CRCs and paired normal colonic mucosa samples. Our strategy resulted in a bAb that specifically triggers EGFR degradation in LGR5+ CSCs and that exhibits unique therapeutic properties such as potent growth inhibition of KRAS mutant CRCs, blockade of metastasis initiation in preclinical models and minimal toxicity towards normal LGR5+ colon stem cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-29T12:53:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004585","title":"RNA sequencing of chondrosarcoma","description":"To profile chondrosarcoma patients.","abstract":"To profile chondrosarcoma patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-29T23:26:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004586","title":"Cerebral organoid model reveals excessive proliferation of human caudal late interneuron progenitors in Tuberous Sclerosis Complex","description":"Although the intricate and prolonged development of the human brain critically distinguishes it from other mammals, our current understanding of neurodevelopmental diseases is largely based on work using animal models. Recent studies revealed that neural progenitors in the human brain are profoundly different from those found in rodent animal models. Moreover, post-mortem studies revealed extensive migration of interneurons into the late-gestational and post-natal human prefrontal cortex that does not occur in rodents. Here, we use cerebral organoids to show that overproduction of mid-gestational human interneurons causes Tuberous Sclerosis Complex (TSC), a severe neuro-developmental disorder associated with mutations in TSC1 and TSC2. We identify a previously uncharacterized population of caudal late interneuron progenitors, the CLIP-cells. In organoids derived from patients carrying heterozygous TSC2 mutations, dysregulation of mTOR signaling leads to CLIP-cell over-proliferation and formation of cortical tubers and subependymal tumors. Surprisingly, second-hit events resulting from copy-neutral loss-of-heterozygosity (cnLOH) are not causative for but occur during the progression of tumor lesions. Instead, EGFR signaling is required for tumor proliferation, opening up a promising approach to treat TSC lesions. Our study demonstrates that the analysis of developmental disorders in organoid models can lead to fundamental insights into human brain development and neuropsychiatric disorders.","abstract":"Although the intricate and prolonged development of the human brain critically distinguishes it from other mammals, our current understanding of neurodevelopmental diseases is largely based on work using animal models. Recent studies revealed that neural progenitors in the human brain are profoundly different from those found in rodent animal models. Moreover, post-mortem studies revealed extensive migration of interneurons into the late-gestational and post-natal human prefrontal cortex that does not occur in rodents. Here, we use cerebral organoids to show that overproduction of mid-gestational human interneurons causes Tuberous Sclerosis Complex (TSC), a severe neuro-developmental disorder associated with mutations in TSC1 and TSC2. We identify a previously uncharacterized population of caudal late interneuron progenitors, the CLIP-cells. In organoids derived from patients carrying heterozygous TSC2 mutations, dysregulation of mTOR signaling leads to CLIP-cell over-proliferation and formation of cortical tubers and subependymal tumors. Surprisingly, second-hit events resulting from copy-neutral loss-of-heterozygosity (cnLOH) are not causative for but occur during the progression of tumor lesions. Instead, EGFR signaling is required for tumor proliferation, opening up a promising approach to treat TSC lesions. Our study demonstrates that the analysis of developmental disorders in organoid models can lead to fundamental insights into human brain development and neuropsychiatric disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-30T11:07:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004587","title":"Project MinE Illumina Infinium HumanMethylation450 (450k) BeadChip data on 2,790 Dutch whole blood samples, including 1,761 ALS patients of which 119 are known carriers of the C9orf72 repeat expansion.","description":"This dataset includes IDAT files from 2,790 blood samples. The samples were profiled using the Illumina Infinium HumanMethylation450 (450k) BeadChip.","abstract":"This dataset includes IDAT files from 2,790 blood samples. The samples were profiled using the Illumina Infinium HumanMethylation450 (450k) BeadChip.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-30T22:21:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004588","title":"Mutational signatures in head and neck cancer (H019)","description":"Genomic alterations are a driving force in the multistep process of head and neck cancer (HNC) and result from the interaction of exogenous environmental exposures and endogenous cellular processes. Each of these processes leaves a characteristic pattern of mutations on the tumor genome providing the unique opportunity to decipher specific signatures of mutational processes operative during HNC pathogenesis and to address their prognostic value. Computational analysis of whole exome sequencing data of the HIPO-HNC (n=83) and TCGA-HNSC (n=506) cohorts revealed five common mutational signatures (COSMIC signature 1, 2, 3, 13 and 16), and demonstrated their significant association with etiological risk factors (tobacco, alcohol and HPV16).","abstract":"Genomic alterations are a driving force in the multistep process of head and neck cancer (HNC) and result from the interaction of exogenous environmental exposures and endogenous cellular processes. Each of these processes leaves a characteristic pattern of mutations on the tumor genome providing the unique opportunity to decipher specific signatures of mutational processes operative during HNC pathogenesis and to address their prognostic value. Computational analysis of whole exome sequencing data of the HIPO-HNC (n=83) and TCGA-HNSC (n=506) cohorts revealed five common mutational signatures (COSMIC signature 1, 2, 3, 13 and 16), and demonstrated their significant association with etiological risk factors (tobacco, alcohol and HPV16).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-07-31T09:03:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004589","title":"YAPSAmanuscript_study","description":null,"abstract":"YAPSA is a user-friendly R/Bioconductor package to perform supervised analysis of mutational signatures. Supervised mutational signature analysis requires considerably less statistical power than de novo extraction of mutational signatures and is therefore particularly suited for the analysis of small series of samples, for example in precision oncology settings. In a manuscript describing the functionalities and usage of YAPSA, we discuss two cases from the molecular tumor boards NCT-MASTER who underwent whole genome sequencing with matched normal control.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004590","title":"Whole metagenomic sequencing samples of the gut microbiome of healthy donors from the Milieu intérieur cohort","description":null,"abstract":"To investigate diversity in the gut microbiome of healthy individuals, we generated shotgun metagenomics data from 1,359 gut microbiome samples from 946 healthy donors of the Milieu Intérieur cohort.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004591","title":"A Universal Gut Microbiome-Derived Signature Predicts Cirrhosis","description":null,"abstract":"Dysregulation of the gut microbiome has been implicated in the progression of nonalcoholic fatty liver disease (NAFLD) to advanced fibrosis and cirrhosis. To determine the diagnostic capacity of this association, stool microbiomes were compared across 163 well-characterized participants encompassing non-NAFLD controls, NAFLD-cirrhosis patients and their first-degree relatives. Interrogation of shotgun metagenomic and untargeted metabolomic profiles using the Random Forest machine learning algorithm and differential abundance analysis identified discrete metagenomic and metabolomic signatures that were similarly effective in detecting cirrhosis (diagnostic accuracy 0.91, AUC). Combining the metagenomic signature with age and serum albumin levels accurately distinguished cirrhosis in etiologically and genetically distinct cohorts from geographically separated regions. Additional inclusion of serum aspartate aminotransferase levels, which are increased in cirrhosis patients, enabled discrimination of cirrhosis from earlier stages of fibrosis. These findings demonstrate that a core set of gut microbiome species may offer universal utility as a non-invasive diagnostic test for cirrhosis.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004592","title":"SNP array files, IDAT files, from 34 members of a Family with a high prevalence of psychosis","description":"We investigated the genetic causes of major mental disorders (MMDs) including schizophrenia, bipolar disorder I, major depressive disorder, and attention deficit hyperactive disorder, in a large family pedigree from Alpujarras, South of Spain, a region with a high prevalence of psychotic disorders. We applied a systematic genomic approach based on karyotyping (N=4), genotyping by genome-wide SNP array (N=33), whole-exome sequencing (N=4), and whole-genome sequencing (N=12). We performed genome-wide linkage analysis, family-based association analysis, and polygenic risk score estimates. Significant linkage was obtained at chromosome 9 (9q33.1-33.2, LOD score= 4.11), a suggestive region that contains five candidate genes ASTN2, BRINP1, C5, TLR4, and TRIM32, previously associated to MMDs. Comprehensive analysis associated the MMD phenotype with genes of the immune system with dual brain functions. Moreover, the psychotic phenotype was enriched for genes involved in synapsis. These results should be considered once studying the genetics of psychiatric disorders in other families, especially the ones from the same region, since founder effects may be related to the high prevalence.","abstract":"We investigated the genetic causes of major mental disorders (MMDs) including schizophrenia, bipolar disorder I, major depressive disorder, and attention deficit hyperactive disorder, in a large family pedigree from Alpujarras, South of Spain, a region with a high prevalence of psychotic disorders. We applied a systematic genomic approach based on karyotyping (N=4), genotyping by genome-wide SNP array (N=33), whole-exome sequencing (N=4), and whole-genome sequencing (N=12). We performed genome-wide linkage analysis, family-based association analysis, and polygenic risk score estimates. Significant linkage was obtained at chromosome 9 (9q33.1-33.2, LOD score= 4.11), a suggestive region that contains five candidate genes ASTN2, BRINP1, C5, TLR4, and TRIM32, previously associated to MMDs. Comprehensive analysis associated the MMD phenotype with genes of the immune system with dual brain functions. Moreover, the psychotic phenotype was enriched for genes involved in synapsis. These results should be considered once studying the genetics of psychiatric disorders in other families, especially the ones from the same region, since founder effects may be related to the high prevalence.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-01T17:34:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004593","title":"Somatic mutations in healthy and leukemic blood progenitors reveal evolutionary mechanisms underlying childhood leukemia and differential patient outcome","description":null,"abstract":"The acquisition of oncogenic mutations with age is believed to be rate limiting for carcinogenesis. However, the incidence of leukemia in children is higher than in young adults yet their cells are less damaged by age. Here, we compared by whole genome sequencing individual hematopoietic stem and progenitor cells (HSPCs) and pediatric acute myeloid leukemia (pAML) of the same leukemic bone marrow as well as nonmatching healthy HSPCs. We found that the number of clonal mutations in the majority of pAML cases was increased and mutational process contribution altered as compared to normal HSPCs, which could be explained by altered selection dynamics early in life. Surprisingly, pAML cases with an overall mutation burden comparable to age matched healthy HSPCs showed worse survival. Our study provides new insights into the etiology of pAML and underscores the clinical potential of whole genome sequencing in pediatric leukemia.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-03T09:58:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004594","title":"Molecular sub-classification of hormone receptor-positive breast cancer","description":"Patients with estrogen and/or progesterone receptor-positive breast cancer benefit from hormonal treatment, yet high global death burdens due to high prevalence and long-term recurrence risk call for biomarkers to guide additional treatment approaches. From a prospective, observational study of postmenopausal early breast cancer patients treated with tamoxifen or aromatase inhibitors gene expression analyses of 612 tumors was performed using the NanoString® Breast Cancer 360 panel. We identified novel gene expression signatures, i.e. BRCAness and Tumor Inflammation Signature (associated with high tumor lymphocyte infiltration), that may aid to select high-risk patients in order to improve adjuvant treatment by targeting DNA repair deficiency or immune-checkpoints in addition to standard chemo-endocrine treatment. The overall goal is to foster novel concepts for a stratified early breast cancer management.","abstract":"Patients with estrogen and/or progesterone receptor-positive breast cancer benefit from hormonal treatment, yet high global death burdens due to high prevalence and long-term recurrence risk call for biomarkers to guide additional treatment approaches. From a prospective, observational study of postmenopausal early breast cancer patients treated with tamoxifen or aromatase inhibitors gene expression analyses of 612 tumors was performed using the NanoString® Breast Cancer 360 panel. We identified novel gene expression signatures, i.e. BRCAness and Tumor Inflammation Signature (associated with high tumor lymphocyte infiltration), that may aid to select high-risk patients in order to improve adjuvant treatment by targeting DNA repair deficiency or immune-checkpoints in addition to standard chemo-endocrine treatment. The overall goal is to foster novel concepts for a stratified early breast cancer management.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-05T09:38:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004595","title":"Using human induced pluripotent stem cell-derived oligodendrocytes to explore cellular phenotypes associated with t(1;11) translocation.","description":"Although the underlying neurobiology of major mental illness (MMI) remains unknown, emerging evidence implicates a role for oligodendrocyte-myelin abnormalities. Here, we took advantage of a large family carrying a balanced t(1;11) translocation, which substantially increases risk of MMI, to undertake both diffusion tensor imaging (DTI) and cellular studies to evaluate the consequences of the t(1;11) translocation on white matter structural integrity and oligodendrocyte-myelin biology (this translocation disrupts among others the DISC1 gene which plays a crucial role in brain development). At a cellular level, we observe dysregulation of key pathways controlling oligodendrocyte development and morphogenesis in induced pluripotent stem cell (iPSC) case derived oligodendrocytes.","abstract":"Although the underlying neurobiology of major mental illness (MMI) remains unknown, emerging evidence implicates a role for oligodendrocyte-myelin abnormalities. Here, we took advantage of a large family carrying a balanced t(1;11) translocation, which substantially increases risk of MMI, to undertake both diffusion tensor imaging (DTI) and cellular studies to evaluate the consequences of the t(1;11) translocation on white matter structural integrity and oligodendrocyte-myelin biology (this translocation disrupts among others the DISC1 gene which plays a crucial role in brain development). At a cellular level, we observe dysregulation of key pathways controlling oligodendrocyte development and morphogenesis in induced pluripotent stem cell (iPSC) case derived oligodendrocytes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-05T15:45:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004596","title":"A GWAS for cutaneous leishmaniasis in Brazil","description":"Our goal was to identify genetic risk factors for cutaneous leishmaniasis (CL) caused by Leishmania braziliensis.  Genotyping 2066 CL cases and 2046 controls using Illumina HumanCoreExomeBeadChips provided data for 4,498,586 imputed single nucleotide variants (SNVs).  Genome-wide association testing using linear mixed models took account of genetic diversity/ethnicity/admixture. Post-GWAS positional, expression quantitative trait locus (eQTL), and chromatin interaction mapping was performed in FUMA.  Transcriptional data were compared between lesions and normal skin, and cytokines measured using flow cytometry and Bioplex assay.","abstract":"Our goal was to identify genetic risk factors for cutaneous leishmaniasis (CL) caused by Leishmania braziliensis.  Genotyping 2066 CL cases and 2046 controls using Illumina HumanCoreExomeBeadChips provided data for 4,498,586 imputed single nucleotide variants (SNVs).  Genome-wide association testing using linear mixed models took account of genetic diversity/ethnicity/admixture. Post-GWAS positional, expression quantitative trait locus (eQTL), and chromatin interaction mapping was performed in FUMA.  Transcriptional data were compared between lesions and normal skin, and cytokines measured using flow cytometry and Bioplex assay.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-06T07:54:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004597","title":"Gene expression profiles of disseminated breast cancer cells","description":null,"abstract":"Although thousands of breast cancer cells disseminate and home to bone marrow until primary surgery, usually less than a handful will succeed in establishing manifest metastases months to years later. To identify signals that support survival or outgrowth in patients, we profile rare bone marrow-derived disseminated cancer cells (DCCs) long before manifestation of metastasis and identify IL6/PI3K-signaling as a candidate pathway for DCC activation. Surprisingly, and similar to mammary epithelial cells, DCCs lack membranous IL6 receptor expression and mechanistic dissection reveals IL6 trans-signaling to regulate a stem-like state of mammary epithelial cells via gp130. Responsiveness to IL6 trans-signals is found to be niche-dependent as bone marrow stromal and endosteal cells down-regulate gp130 in premalignant mammary epithelial cells as opposed to vascular niche cells. PIK3CA activation renders cells independent from IL6 trans-signaling. Consistent with a bottleneck function of microenvironmental DCC control, we find PIK3CA mutations highly associated with late-stage metastatic cells while being extremely rare in early DCCs. Our data suggest that the initial steps of metastasis formation are often not cancer cell-autonomous, but also depend on microenvironmental signals.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-06T10:15:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004598","title":"Gene expression profiles of disseminated breast cancer cells","description":null,"abstract":"Although thousands of breast cancer cells disseminate and home to bone marrow until primary surgery, usually less than a handful will succeed in establishing manifest metastases months to years later. To identify signals that support survival or outgrowth in patients, we profile rare bone marrow-derived disseminated cancer cells (DCCs) long before manifestation of metastasis and identify IL6/PI3K-signaling as a candidate pathway for DCC activation. Surprisingly, and similar to mammary epithelial cells, DCCs lack membranous IL6 receptor expression and mechanistic dissection reveals IL6 trans-signaling to regulate a stem-like state of mammary epithelial cells via gp130. Responsiveness to IL6 trans-signals is found to be niche-dependent as bone marrow stromal and endosteal cells down-regulate gp130 in premalignant mammary epithelial cells as opposed to vascular niche cells. PIK3CA activation renders cells independent from IL6 trans-signaling. Consistent with a bottleneck function of microenvironmental DCC control, we find PIK3CA mutations highly associated with late-stage metastatic cells while being extremely rare in early DCCs. Our data suggest that the initial steps of metastasis formation are often not cancer cell-autonomous, but also depend on microenvironmental signals.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004599","title":"Whole Exome Sequences from Iberian Roma samples","description":"Study of high-depth Roma whole exomes to analyse the impact of complex demography on the functional genomic variation. This study also includes genome-wide array data of Iberian Roma individuals","abstract":"Study of high-depth Roma whole exomes to analyse the impact of complex demography on the functional genomic variation. This study also includes genome-wide array data of Iberian Roma individuals","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-06T11:18:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004600","title":"A Universal Gut Metagenomic-Derived Signature Predicts Cirrhosis","description":"Dysregulation of the gut microbiome has been implicated in the progression of nonalcoholic fatty liver disease (NAFLD) to advanced fibrosis and cirrhosis. To determine the diagnostic capacity of this association, stool microbiomes were compared across 163 well-characterized participants encompassing non-NAFLD controls, NAFLD-cirrhosis patients and their first-degree relatives. Interrogation of shotgun metagenomic and untargeted metabolomic profiles using the Random Forest machine learning algorithm and differential abundance analysis identified discrete metagenomic and metabolomic signatures that were similarly effective in detecting cirrhosis (diagnostic accuracy 0.91, AUC). Combining the metagenomic signature with age and serum albumin levels accurately distinguished cirrhosis in etiologically and genetically distinct cohorts from geographically separated regions. Additional inclusion of serum aspartate aminotransferase levels, which are increased in cirrhosis patients, enabled discrimination of cirrhosis from earlier stages of fibrosis. These findings demonstrate that a core set of gut microbiome species may offer universal utility as a non-invasive diagnostic test for cirrhosis.","abstract":"Dysregulation of the gut microbiome has been implicated in the progression of nonalcoholic fatty liver disease (NAFLD) to advanced fibrosis and cirrhosis. To determine the diagnostic capacity of this association, stool microbiomes were compared across 163 well-characterized participants encompassing non-NAFLD controls, NAFLD-cirrhosis patients and their first-degree relatives. Interrogation of shotgun metagenomic and untargeted metabolomic profiles using the Random Forest machine learning algorithm and differential abundance analysis identified discrete metagenomic and metabolomic signatures that were similarly effective in detecting cirrhosis (diagnostic accuracy 0.91, AUC). Combining the metagenomic signature with age and serum albumin levels accurately distinguished cirrhosis in etiologically and genetically distinct cohorts from geographically separated regions. Additional inclusion of serum aspartate aminotransferase levels, which are increased in cirrhosis patients, enabled discrimination of cirrhosis from earlier stages of fibrosis. These findings demonstrate that a core set of gut microbiome species may offer universal utility as a non-invasive diagnostic test for cirrhosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-06T13:59:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004601","title":"The endometrial transcription landscape of MRKH syndrome","description":"The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (OMIM 277000) is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. While genetic causes have been identified for a small subset of patients and epigenetic mechanisms presumably contribute to the pathogenic unfolding, too, the etiology of the syndrome has remained largely enigmatic. A comprehensive understanding of gene activity in the context of the disease is crucial to identify etiological components and their potential interplay. So far, this understanding is lacking, primarily due to the scarcity of samples and suitable tissue.\nIn order to close this gap, we profiled endometrial tissue of uterus rudiments in a large cohort of MRKH patients using RNA-seq and thereby provide a genome-wide view on the altered transcription landscape of the MRKH syndrome.","abstract":"The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (OMIM 277000) is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. While genetic causes have been identified for a small subset of patients and epigenetic mechanisms presumably contribute to the pathogenic unfolding, too, the etiology of the syndrome has remained largely enigmatic. A comprehensive understanding of gene activity in the context of the disease is crucial to identify etiological components and their potential interplay. So far, this understanding is lacking, primarily due to the scarcity of samples and suitable tissue.\nIn order to close this gap, we profiled endometrial tissue of uterus rudiments in a large cohort of MRKH patients using RNA-seq and thereby provide a genome-wide view on the altered transcription landscape of the MRKH syndrome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-07T09:03:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004602","title":"The Precision Medicine in Liver Cancer with Recurrence across an Asia-pacific Network","description":null,"abstract":"Hepatocellular carcinoma (HCC) is the 2nd most important cause of cancer deaths in the world. The outcomes of treatment in HCC are poor compared to other common cancers because there are no good systemic therapy drugs. We designed a prospective study that will involve 5 different sites within the established Asia-Pacific Hepatocellular Carcinoma Trials Group to study both genetics as well as immune profiles of HCC in different ethnicities. In this study, patients will be followed-up and at recurrence the tissues to understand the evolution of disease progression.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004603","title":"Whole Exome Sequencing of High grade T1 non-muscle invasive bladder cancer","description":"High-grade T1 (HGT1) bladder cancer (BC) is the highest risk subtype of non-muscle-invasive BC with unpredictable outcome and poorly understood risk factors. Here we performed whole exome sequencing across 61 HGT1 samples to identify genomic predictors of good outcome, recurrence or progression. This study includes somatic mutation calls and clinical data for 61 HGT1 tumors.","abstract":"High-grade T1 (HGT1) bladder cancer (BC) is the highest risk subtype of non-muscle-invasive BC with unpredictable outcome and poorly understood risk factors. Here we performed whole exome sequencing across 61 HGT1 samples to identify genomic predictors of good outcome, recurrence or progression. This study includes somatic mutation calls and clinical data for 61 HGT1 tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-09T14:29:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004604","title":"Effects_of_Chemotherapy_on_the_Somatic_Mutational_Landscape_in_Normal_Human_Tissue___DuplexSeq","description":"This study is investigating the effects of chemotherapy drugs used in cancer treatment on the somatic mutational landscape in normal human tissues. The samples used in this study have been taken from rapid autopsies of patients who have undergone chemotherapy using drugs thought to cause mutations in the DNA. Structures from a variety of tissues will be dissected using LCM and whole genome sequences will be produced in order to assess mutational burdens and signatures.","abstract":"This study is investigating the effects of chemotherapy drugs used in cancer treatment on the somatic mutational landscape in normal human tissues. The samples used in this study have been taken from rapid autopsies of patients who have undergone chemotherapy using drugs thought to cause mutations in the DNA. Structures from a variety of tissues will be dissected using LCM and whole genome sequences will be produced in order to assess mutational burdens and signatures.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004605","title":"Healthy_Aging_Thymus","description":"Single cell RNA sequencing of immune and non-immune cells from healthy ageing thymus\n\nThymus is a primary lymphoid organ that creates an environment for the T lymphocyte precursors differentiation into the naive T cells, which involves TCR gene rearrangement, negative and positive selection. Despite thymus critical function for the recognition of the pathogens it starts to atrophy very early in life. Thymic Epithelial Space (TES), where thymocyte education occurs, starts to decline rapidly just after birth, while with the onset of puberty thymus  is also progressively replaced with adipose tissue. This leads to a reduced naive T cell output,which decreases an organism's ability to recognize pathogens.\nIn our lab, we have already collected and characterized cell type composition and gene regulatory networks of the fetal tand adult human thymus (Park et al, Science 2020). In the current project we plan to expand the number of paediatric and adult samples in the study with the aim to understand how the process of thymic involution happens. We will use single-cell transcriptomics to zoom on changes that occur in immune and non-immune cell types in different phases of thymic involution with the hope to understand which gene expression changes are causal for the thymic involution process and how naïve T cell production can be increased in elderly.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Single cell RNA sequencing of immune and non-immune cells from healthy ageing thymus\n\nThymus is a primary lymphoid organ that creates an environment for the T lymphocyte precursors differentiation into the naive T cells, which involves TCR gene rearrangement, negative and positive selection. Despite thymus critical function for the recognition of the pathogens it starts to atrophy very early in life. Thymic Epithelial Space (TES), where thymocyte education occurs, starts to decline rapidly just after birth, while with the onset of puberty thymus  is also progressively replaced with adipose tissue. This leads to a reduced naive T cell output,which decreases an organism's ability to recognize pathogens.\nIn our lab, we have already collected and characterized cell type composition and gene regulatory networks of the fetal tand adult human thymus (Park et al, Science 2020). In the current project we plan to expand the number of paediatric and adult samples in the study with the aim to understand how the process of thymic involution happens. We will use single-cell transcriptomics to zoom on changes that occur in immune and non-immune cell types in different phases of thymic involution with the hope to understand which gene expression changes are causal for the thymic involution process and how naïve T cell production can be increased in elderly.  \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004606","title":"Primary and recurrent High-Grade Glioma sequencing study","description":null,"abstract":"Immune checkpoint inhibitors are currently tested in clinical trials, but glioblastoma is a “cold tumor” which actively suppresses antitumor immunity. Understanding genomic and transcriptomic alterations for recurrence may offer new clues for improvements over current treatments. Using targeted sequencing of cancer-related genes and transcriptomics, we identified profiles of single nucleotide variations, small insertions and deletions, copy number aberrations (CNAs), as well as gene expression changes and pathways deregulation in 16 pairs of primary and recurrent HGGs. Most of the somatic mutations identified in primary HGGs were not detected after relapse, suggesting a sub-clone substitution during the tumor progression. We found a novel frame-shift insertion in the ZNF384 gene which may contribute to extracellular matrix remodeling. CNAs analysis showed an inverse correlation of focal CNAs in EGFR and PTEN genes.\n\nTranscriptomic analysis revealed that genes involved in mRNA splicing, cell cycle and DNA repair are down-regulated, while genes related to interferon signaling and PI metabolism are up-regulated in secondary HGGs when compared to primary ones. In-silico analysis of the tumor microenvironment identified M2 macrophages and immature dendritic cells as enriched in recurrent HGGs, suggesting a more prominent immunosuppressive signature. Accumulation of those cells in recurrent HGGs was validated by immunostaining. Our findings point to an important transcriptomic deregulation and a more prominent infiltration of immature dendritic cells in recurrent HGG, which are new factors that should be considered while introducing frontline immunotherapies in GBM.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004607","title":"WGS Taiwanese UTUCs","description":null,"abstract":"Whole-genome sequencing data of tumor and adjacent normal tissues of 12 patients with upper tract urothelial carcinoma. The data was complemented by duplex sequencing data of the same tissues as well as some urine and blood samples. The aim of the study was to establish the feasibility of using duplex sequencing technology to detected AA-mutagenesis in non-invasive samples such as blood and urine.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004608","title":"Single_cell_macrophage_differentiation","description":"Single cell macrophage differentiation. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Human induced pluripotent stem cells (hiPSC) are differentiated to macrophages through an embrioid body based protocol. Several hiPSC lines are differentiated and several timepoints are analysed at using  single cell 3' gene expression 10X  technology. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004609","title":"Multiple neoplasia in a patient with Gitelman syndrome harboring germline monoallelic MUTYH mutation","description":"Gitelman syndrome is a rare, recessively-inherited disease characterized by chronic hypokalemia and hypomagnesemia as a result of defective electrolyte co-transport at the level of the distal convoluted tubule of the kidney. Here, we present the first report of a patient with Gitelman syndrome who developed multiple neoplasia including colorectal polyposis, synchronous colorectal cancers, recurrent breast fibroadenomata and a desmoid tumor. Whole exome sequencing confirmed germline compound heterozygous mutations of c.179C&gt;T and c.1326C&gt;G in SLC12A3, and in addition, identified a monoallelic germline c.934-2A&gt;G splice site mutation in MUTYH. In vitro, magnesium deficiency potentiated oxidative DNA damage in lymphoblastoid cell lines derived from the same patient. We postulate that monoallelic MUTYH mutations may manifest in the presence of cooperative non-genetic mechanisms, in this case possibly magnesium deficiency from Gitelman syndrome.","abstract":"Gitelman syndrome is a rare, recessively-inherited disease characterized by chronic hypokalemia and hypomagnesemia as a result of defective electrolyte co-transport at the level of the distal convoluted tubule of the kidney. Here, we present the first report of a patient with Gitelman syndrome who developed multiple neoplasia including colorectal polyposis, synchronous colorectal cancers, recurrent breast fibroadenomata and a desmoid tumor. Whole exome sequencing confirmed germline compound heterozygous mutations of c.179C&gt;T and c.1326C&gt;G in SLC12A3, and in addition, identified a monoallelic germline c.934-2A&gt;G splice site mutation in MUTYH. In vitro, magnesium deficiency potentiated oxidative DNA damage in lymphoblastoid cell lines derived from the same patient. We postulate that monoallelic MUTYH mutations may manifest in the presence of cooperative non-genetic mechanisms, in this case possibly magnesium deficiency from Gitelman syndrome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004610","title":"RRBS MDACC Lung PreCancer","description":"To study the evolution of DNA methylation at genome level and methylation intra-tumor heterogeneity (ITH) during early lung carcinogenesis, we performed multiregional reduced representation bisulfite sequencing (RRBS) of 62 resected lung nodules from 39 patients including atypical adenomatous hyperplasia (AAH, n=14), adenocarcinoma in situ (AIS, n=15), minimally invasive adenocarcinoma (MIA, n=22), and invasive adenocarcinoma (ADC, n=11).","abstract":"To study the evolution of DNA methylation at genome level and methylation intra-tumor heterogeneity (ITH) during early lung carcinogenesis, we performed multiregional reduced representation bisulfite sequencing (RRBS) of 62 resected lung nodules from 39 patients including atypical adenomatous hyperplasia (AAH, n=14), adenocarcinoma in situ (AIS, n=15), minimally invasive adenocarcinoma (MIA, n=22), and invasive adenocarcinoma (ADC, n=11).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-14T09:59:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004611","title":"Prime editing for functional repair in patient-derived disease models","description":"Prime editing is a novel genome editing technology using fusion proteins of Cas9-nickase and reverse transcriptase, that holds promise to correct a wide variety of genetic defects.\nWe succeeded in efficient prime editing and functional recovery of disease-causing mutations in patient-derived liver and intestinal stem cell organoids. Whole genome sequencing of did not detect off-target mutations or a mutational signature induced by prime editing.","abstract":"Prime editing is a novel genome editing technology using fusion proteins of Cas9-nickase and reverse transcriptase, that holds promise to correct a wide variety of genetic defects.\nWe succeeded in efficient prime editing and functional recovery of disease-causing mutations in patient-derived liver and intestinal stem cell organoids. Whole genome sequencing of did not detect off-target mutations or a mutational signature induced by prime editing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-14T12:25:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004612","title":"High throughput profiling of undifferentiated pleomorphic sarcomas identifies two main subgroups with distinct immune contexture, clinical outcome and sensitivity to targeted therapies","description":null,"abstract":"Undifferentiated pleomorphic sarcoma (UPS) is the most frequent, aggressive and less-characterized sarcoma subtype. This study aims to assess UPS molecular characteristics and identify specific therapeutic targets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-14T18:10:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004613","title":"PCa-LINES","description":"PCa-LINES: Ribo-minus RNA-seq of 4 patient samples and 2 PCa cell lines\n----\nDetection of fusion transcripts and their genomic breakpoints from RNA sequencing data\nYouri Hoogstrate, Malgorzata A. Komor, René Böttcher, Job van Riet, Harmen J. G. van de Werken, Stef van Lieshout, Ralf Hoffmann, Evert van den Broek, Anne S. Bolijn, Natasja Dits, Daoud Sie, David van der Meer, Floor Pepers, Chris H. Bangma, Geert J. L. H. van Leenders, Marcel Smid, Pim French, John W.M. Martens, Wilbert van Workum, Peter J. van der Spek, Bart Janssen, Eric Caldenhoven, Christian Rausch, Mark de Jong, Andrew P. Stubbs, Gerrit A. Meijer, Remond J.A. Fijneman, Guido Jenster\nbioRxiv 2021.05.17.441778; doi: https://doi.org/10.1101/2021.05.17.441778\nhttps://www.biorxiv.org/content/10.1101/2021.05.17.441778v1","abstract":"PCa-LINES: Ribo-minus RNA-seq of 4 patient samples and 2 PCa cell lines\n----\nDetection of fusion transcripts and their genomic breakpoints from RNA sequencing data\nYouri Hoogstrate, Malgorzata A. Komor, René Böttcher, Job van Riet, Harmen J. G. van de Werken, Stef van Lieshout, Ralf Hoffmann, Evert van den Broek, Anne S. Bolijn, Natasja Dits, Daoud Sie, David van der Meer, Floor Pepers, Chris H. Bangma, Geert J. L. H. van Leenders, Marcel Smid, Pim French, John W.M. Martens, Wilbert van Workum, Peter J. van der Spek, Bart Janssen, Eric Caldenhoven, Christian Rausch, Mark de Jong, Andrew P. Stubbs, Gerrit A. Meijer, Remond J.A. Fijneman, Guido Jenster\nbioRxiv 2021.05.17.441778; doi: https://doi.org/10.1101/2021.05.17.441778\nhttps://www.biorxiv.org/content/10.1101/2021.05.17.441778v1","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-17T10:34:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004614","title":"Patient-tailored design for selective co-inhibition of leukemic cell subpopulations","description":"The extensive primary and secondary drug resistance in many cancer types requires rational approaches to design personalized and selective combinatorial therapies that do not only show synergistic effect in overall cancer cell killing but also result in minimal toxic side effects on non-malignant cells. To address the combinatorial explosion in the number of relevant combinations, we implemented a machine learning approach that prioritizes patient-customized drug combinations with a desired synergy-efficacy-toxicity balance by combining single-cell RNA-sequencing with ex vivo single-agent testing in scarce patient-derived primary cells. When applied to two diagnostic and two refractory AML patient cases, each with a different genetic background, our integrated approach accurately predicted patient-specific combinations that were shown to result not only in synergistic cancer cell co-inhibition but were also capable of targeting specific AML cell subpopulations that emerge in differing stages of disease pathogenesis or treatment regimens. Our data-driven approach provides an unbiased means for systematic identification of personalized combinatorial regimens that selectively co-inhibit leukemic cells while avoiding inhibition of non-malignant cells, and highlight the relevance of considering cell heterogeneity for personalized cancer therapy.","abstract":"The extensive primary and secondary drug resistance in many cancer types requires rational approaches to design personalized and selective combinatorial therapies that do not only show synergistic effect in overall cancer cell killing but also result in minimal toxic side effects on non-malignant cells. To address the combinatorial explosion in the number of relevant combinations, we implemented a machine learning approach that prioritizes patient-customized drug combinations with a desired synergy-efficacy-toxicity balance by combining single-cell RNA-sequencing with ex vivo single-agent testing in scarce patient-derived primary cells. When applied to two diagnostic and two refractory AML patient cases, each with a different genetic background, our integrated approach accurately predicted patient-specific combinations that were shown to result not only in synergistic cancer cell co-inhibition but were also capable of targeting specific AML cell subpopulations that emerge in differing stages of disease pathogenesis or treatment regimens. Our data-driven approach provides an unbiased means for systematic identification of personalized combinatorial regimens that selectively co-inhibit leukemic cells while avoiding inhibition of non-malignant cells, and highlight the relevance of considering cell heterogeneity for personalized cancer therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-17T11:28:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004615","title":"Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer","description":null,"abstract":"Molecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment options and its high genomic heterogeneity. We profiled minimally-invasive plasma circulating tumor DNA (ctDNA) samples from 104 mUC patients, and compared to same-patient tumour tissue obtained during invasive surgery. Patient ctDNA abundance was independently prognostic for overall survival in patients initiating first-line systemic therapy. Importantly, ctDNA analysis reproduced the somatic driver genome as described from tissue-based cohorts. Furthermore, mutation concordance between ctDNA and matched tumor tissue was 83.4%, enabling benchmarking of proposed clinical biomarkers. While 90% of mutations were identified across serial ctDNA samples, concordance for serial tumor tissue was below 50%. Overall, our findings demonstrate that ctDNA analysis is a reliable and practical method for genomic profiling of mUC, and mitigates against disease undersampling inherent to studying archival primary tumor foci. We urge the incorporation of cell-free DNA profiling into molecularly-guided clinical trials for mUC.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-17T19:27:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004616","title":"ccRCC Invasion and Metastatic Competence Determinants","description":null,"abstract":"Not all invasive tumors are metastatic. Traits associated with invasive tumors that metastasize are unknown and critical for clinical management of cancer.  Here, we addressed this knowledge gap by analyzing whole exome and transcriptomes of 275 matched tumor and invasive intravascular tumor thrombus samples from 82 ccRCC patients. We report ability to invade is directed by a reversible adaptive response enforced by the immediate early induced transcription factors and is not an impediment to metastatic progression, as diverse oncogenomic tumors in geospatial proximity of renal vein invade and extend as intravascular tumor thrombus. Systematic analysis of metastatic and non-metastatic invasive intravascular tumors revealed significant enrichment for tissue architectural patterns associated with aggressive disease, distinct stromal composition and enhanced mTOR signaling response as key determinants of metastatic competence. mTOR inhibition using rapalogs resulted in reduced tumor progression and metastatic incidence in patient derived xenografts and metastatic ccRCC models. Together, our  data identify an independent gene signature and traits associated with metastatic competence that can be targeted to limit disease progression and metastasis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004617","title":"Molecular subsets in renal cancer determine outcome to checkpoint and angiogenesis blockade","description":null,"abstract":"We conducted integrated multi-omics evaluation of 823 tumors from advanced renal cell carcinoma (RCC) patients and identified molecular subsets associated with differential clinical outcomes to angiogenesis blockade alone or with a checkpoint inhibitor. Unsupervised transcriptomic analysis revealed six molecular subsets with distinct angiogenesis, immune, cell cycle, metabolism, and stromal programs. While sunitinib was effective in subsets with high angiogenesis, atezolizumab+bevacizumab improved clinical benefit in tumors with high T-effector and/or cell cycle transcription. Somatic mutations in PBRM1 and KDM5C associated with high angiogenesis and AMPK/Fatty acid oxidation gene expression, while CDKN2A/B and TP53 alterations were more prevalent in tumors with increased cell cycle and anabolic metabolism. Sarcomatoid tumors exhibited low prevalence of PBRM1 mutations and angiogenesis markers, frequent CDKN2A/B, BAP1 and TP53 alterations, and increased PD-L1 expression. These findings can be applied to molecularly stratify advanced RCC patients, explain improved outcomes of sarcomatoid tumors to checkpoint blockade, and develop personalized therapies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004618","title":"RNA-Seq of monocytes sorted from peripheral blood of 6 hospitalised individuals with COVID19 infection and 3 healthy control","description":null,"abstract":"PTX3 is an essential component of humoral innate immunity, involved in resistance to selected pathogens and in the regulation of inflammation. PTX3 plasma levels are associated with poor outcome in systemic inflammatory conditions and vascular pathology. The present study was designed to assess expression and significance of PTX3 in COVID-19. By bioinformatics analysis of public databases PTX3 expression was detected in lung respiratory cell lines exposed to SARS-CoV-2. By analysis at single cell level of COVID-19 circulating mononuclear cells, we found that PTX3 was selectively expressed by monocytes among circulating leukocytes. Moreover, in lung bronchoalveolar lavage fluid, single cell analysis revealed selective expression of PTX3 in neutrophils and macrophages, which play a major role in the pathogenesis of the disease. By immunohistochemistry, PTX3 was expressed by lung myelomocytic cells, type 2 pneumocytes and vascular endothelial cells. PTX3 plasma levels were determined by ELISA in 96 consecutive patients with a laboratory-confirmed diagnosis of COVID-19. Higher PTX3 plasma levels were observed in 52 (54.2%) patients admitted in ICU (median 21.0ng/mL, IQT 15.5-46.3 vs 12.4ng/mL IQT 6.1-20.2 in ward patients; p=0.0017) and in 22 (23%) patients died by 28 days (39.8ng/mL, IQT 20.2-75.7 vs 15.7ng/mL, IQT 8.2-21.6 in survivors; p=0.0001). After determining an optimal PTX3 cut-off for the primary outcome, the Kaplan-Meier curve showed an increased mortality in patients with PTX3&gt;22.25ng/mL (Log-rank tests p&lt;0.0001). In Cox regression model, PTX3&gt;22.25ng/mL showed an adjusted Hazard Ratio (aHR) of 7.6 (95%CI2.45-23.76) in predicting mortality. Performing a multivariate logistic regression including all inflammatory markers (PTX3, ferritin, D-Dimer, IL-6, and CRP), PTX3 was the only marker significantly associated with death (aHR 1.13;95%CI1.02- 1.24; p=0.021). The results reported here suggest that circulating and lung myelomonocytic cells are a major source of PTX3 and that PTX3 plasma levels can serve as a strong prognostic indicator of short-term mortality in COVID-19.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004619","title":"Queensland Melanoma Genomic Biomarker Study","description":"There is a clinical need to identify melanoma patients not likely to benefit from current targeted and immuno-therapy and identify biomarkers that can predict patient outcome. Genomic biomarkers are not yet part of staging but show promising results. The aim of this study was to determine genomic and image-based biomarkers as adverse prognostic factors in stage III/IV melanoma patients with resected disease. We found combining genomic and PET/CT derived biomarkers with current clinical assessment may offer additional prognostic tools to stratify patients in the clinic.","abstract":"There is a clinical need to identify melanoma patients not likely to benefit from current targeted and immuno-therapy and identify biomarkers that can predict patient outcome. Genomic biomarkers are not yet part of staging but show promising results. The aim of this study was to determine genomic and image-based biomarkers as adverse prognostic factors in stage III/IV melanoma patients with resected disease. We found combining genomic and PET/CT derived biomarkers with current clinical assessment may offer additional prognostic tools to stratify patients in the clinic.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-19T03:25:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004620","title":"Understanding_hematopoietic_stem_cell_mobilization_and_engraftment_","description":"This study looks at patients undergoing gene therapy for genetic blood and immune disorders, in particular sickle cell disease. From each patient, single blood HSPC colonies are grown from patient blood mononuclear cells,  bone marrow mononuclear cells, or CD34+ at multiple time points: pre gene transduction, post-transduction,  and post-infusion (at several time points). Whole-genome sequencing will be performed on DNA from these colonies and somatically-acquired mutations will be called. Using these mutations, a phylogeny of these cells can be inferred and further inferences can be made about the gene therapy transduction and engraftment steps.","abstract":"Blood stem cells are the fundamental component of all successful bone marrow transplantations – they are responsible for the longterm successful donor cell graft and the production of all mature blood cell lineages. Robust blood stem cell transplantation therefore is an essential requirement for all gene therapy applications that involve the blood and immune system (e.g., immunodeficiencies, anemias, etc). Often, the limiting factor for successful bone marrow transplantation is the ability to harvest a sufficient number of blood stem cells to ensure robust engraftment and the ability for the blood stem cells to retain their function outside the body while the gene target is being edited. Currently, stem cell number is estimated by the proportion of cells expressing a cell surface protein (CD34), but only a small minority of CD34+ cells are actually functional stem cells, meaning that more direct ways to measure stem cell numbers are essential. Furthermore, a better understanding of how many stem cells are harvested from patients (either directly or through stem cell mobilization protocols) and how many of these harvested stem cells contribute to donor cell production will be essential pieces of information for the better design of patient specific treatment protocols and may also lead to the development of better stem cell retention conditions. \n\nIn an effort to understand these questions in patients with sickle cell disease, we have assembled a multi-center, multi-disciplinary team of experts in gene therapy, stem cell biology, and genomics. Overall, this project builds on the recent discovery that whole genome sequencing approaches in blood stem and progenitor cells can be used to estimate the number of actively contributing blood stem cells in humans (Lee-Six et al., Nature 2018). More than 100,000 spontaneous, genome-wide somatic mutations were identified across 140 single-cell-derived blood stem and progenitor colonies from a healthy 59-year-old man. This allowed a family tree of relatedness to be constructed and population genetics approaches were applied to estimate the clonal dynamics of the stem cell pool. Stem cell population size was shown to grow steadily in early life and reach a stable plateau by adolescence with the number of stem cells actively making white blood cells at any one time being in the range of 50,000-200,000. \n\nThe overall aim of this project is to apply similar techniques in samples obtained from patients prior to and following autologous gene therapy for sickle cell disease in an effort to estimate the number of blood stem cells available for gene therapy. While the project outcomes will be focused on sickle cell disease, the low supply of transplantation material from sickle cell patients requires us to construct analysis pipelines on material from other diseases treated with gene therapy for longer periods (see below). Patient specific baseline data will be obtained from pre-transplantation samples including the construction of a phylogenetic tree of blood stem cell clones. The relative contributions (and origins) of successfully transduced blood stem cells will be determined by assessing samples taken post-transduction and post-transplantation, resulting in the estimation of stem cell numbers available for gene therapy in sickle cell patients.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-20T09:11:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004621","title":"SureTypeSC - accurate genotyping of single-cell SNP array data","description":"We used a collection of single cells from two Coriell cell lines to train and validate a machine learning method for quality assessment of the single cell genotypes","abstract":"We used a collection of single cells from two Coriell cell lines to train and validate a machine learning method for quality assessment of the single cell genotypes","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-20T09:35:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004622","title":"WSSS_Adult_Gut","description":"Transcriptomics profling of human gut.\n\nThe Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through; genetic and genomic analysis, expression analysis, non-identifiable video imaging and cell line and organoid production, as well as, computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequently validate these findings in situ using spatial genomic and imaging technologies e.g. immunohistochemistry, RNAscope, in situ sequencing and spatial transcriptomic analyses.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Transcriptomics profling of human gut.\n\nThe Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through; genetic and genomic analysis, expression analysis, non-identifiable video imaging and cell line and organoid production, as well as, computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequently validate these findings in situ using spatial genomic and imaging technologies e.g. immunohistochemistry, RNAscope, in situ sequencing and spatial transcriptomic analyses.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004623","title":"Single-cell RNA-seq of celiac disease-specific plasma cells","description":"Disease-specific plasma cells (PCs) reactive with transglutaminase 2 (TG2) or deamidated gluten peptides (DGP) are abundant in celiac disease (CeD) gut lesions. Their contribution toward CeD pathogenesis is unclear. We assessed expression of markers associated with PC longevity in 15 untreated and 26 treated CeD patients in addition to 13 non-CeD controls, and performed RNA-sequencing with clonal inference and transcriptomic analysis of 3251 single PCs. We observed antigen-dependent V-gene selection and stereotypic antibodies. Generation of recombinant DGP-specific antibodies revealed a key role of a heavy-chain residue that displays polymorphism, suggesting that immunoglobulin gene polymorphisms may influence CeD-specific antibody responses. We identified transcriptional differences between CeD-specific vs non-disease-specific PCs and between short-lived vs long-lived PCs. The short-lived CD19+CD45+ phenotype dominated in untreated and short-term-treated CeD, in particular among disease-specific PCs but also in the general PC population. Thus, the disease lesion of untreated CeD is characterized by massive accumulation of short-lived PCs that are not only directed against disease-specific antigens.","abstract":"Disease-specific plasma cells (PCs) reactive with transglutaminase 2 (TG2) or deamidated gluten peptides (DGP) are abundant in celiac disease (CeD) gut lesions. Their contribution toward CeD pathogenesis is unclear. We assessed expression of markers associated with PC longevity in 15 untreated and 26 treated CeD patients in addition to 13 non-CeD controls, and performed RNA-sequencing with clonal inference and transcriptomic analysis of 3251 single PCs. We observed antigen-dependent V-gene selection and stereotypic antibodies. Generation of recombinant DGP-specific antibodies revealed a key role of a heavy-chain residue that displays polymorphism, suggesting that immunoglobulin gene polymorphisms may influence CeD-specific antibody responses. We identified transcriptional differences between CeD-specific vs non-disease-specific PCs and between short-lived vs long-lived PCs. The short-lived CD19+CD45+ phenotype dominated in untreated and short-term-treated CeD, in particular among disease-specific PCs but also in the general PC population. Thus, the disease lesion of untreated CeD is characterized by massive accumulation of short-lived PCs that are not only directed against disease-specific antigens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-20T15:44:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004624","title":"16 Year Life History and Genomic Evolution of an ER+ HER2- Breast Cancer","description":"We reconstructed the genomic evolution through the sixteen year history of an ER+ HER2- breast cancer patient to investigate molecular mechanisms of disease relapse and treatment resistance after long term exposure to hormonal therapy. Genomic and transcriptomic profiling was performed on primary breast tumor (2002), initial recurrence (2012) and liver metastasis (2015) tumor samples. Cell free DNA analysis was performed at eleven timepoints (2015-2017).This phylogenetic reconstruction of the life history of a single patient's cancer as well as monitoring tumor progression through liquid biopsies with the detection of a resistant clone harboring a de-novo ESR1 E380Q mutation allowed for uncovering the molecular mechanisms leading to initial relapse, metastatic spread and treatment resistance.","abstract":"We reconstructed the genomic evolution through the sixteen year history of an ER+ HER2- breast cancer patient to investigate molecular mechanisms of disease relapse and treatment resistance after long term exposure to hormonal therapy. Genomic and transcriptomic profiling was performed on primary breast tumor (2002), initial recurrence (2012) and liver metastasis (2015) tumor samples. Cell free DNA analysis was performed at eleven timepoints (2015-2017).This phylogenetic reconstruction of the life history of a single patient's cancer as well as monitoring tumor progression through liquid biopsies with the detection of a resistant clone harboring a de-novo ESR1 E380Q mutation allowed for uncovering the molecular mechanisms leading to initial relapse, metastatic spread and treatment resistance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-20T20:17:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004625","title":"The Genetic Basis of Preeclampsia in an Andean Population Adapted to High Altitude","description":null,"abstract":"To investigate the genetic basis of preeclampsia and its relationship to altitude, we characterized genetic diversity in a cohort of Andean families (N=883) from Puno, Peru, a high altitude city above 3,500 m. Our study collected genetic samples and medical records from case-control trios and duos, thus allowing for measurement of maternal, paternal and fetal genetic factors on preeclampsia risk. We generated high-density genotype data at over 400,000 positions across the genome, and used these data to determine ancestry patterns and map associations between genetic variants and preeclampsia phenotype. We also generated capture sequencing data from a subset of the study cohort focusing on genomic regions surrounding our top candidate hits.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-21T01:11:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004626","title":"Bromodomain and Extraterminal Inhibition Blocks Inflammation-Induced Cardiac Dysfunction and SARS-CoV2 Infection","description":"Bulk RNA-sequencing of lungs and hearts from a SARS-CoV2 infection study. K18-hACE2 mice (strain B6.Cg-Tg(K18-ACE2)2Prlmn/J) were infected with SARS-CoV2 (10 mice) and there were 5 non-infected controls. Infected mice were given 67 mg/kg INCB054329 or a vehicle control [30% (m/v) Kolliphor 15 HS (Sigma) in PBS] at 1, 2 and 3 days post infection. Mice were euthanized and organs harvested at 4 d.p.i. Libraries were prepared from ribosomal depleted total RNA and sequenced on a NextSeq 500/550 v2 (Illumina) with 150 bp reads.","abstract":"Bulk RNA-sequencing of lungs and hearts from a SARS-CoV2 infection study. K18-hACE2 mice (strain B6.Cg-Tg(K18-ACE2)2Prlmn/J) were infected with SARS-CoV2 (10 mice) and there were 5 non-infected controls. Infected mice were given 67 mg/kg INCB054329 or a vehicle control [30% (m/v) Kolliphor 15 HS (Sigma) in PBS] at 1, 2 and 3 days post infection. Mice were euthanized and organs harvested at 4 d.p.i. Libraries were prepared from ribosomal depleted total RNA and sequenced on a NextSeq 500/550 v2 (Illumina) with 150 bp reads.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004627","title":"GWAS in bullous pemphigoid in Germans","description":"Genome-wide association study of bullous pemphigoid in Germans, using 446 BP patients and 433 age- and sex- matched controls. 6 SNPs in the HLA locus were found to be of genome-wide significance.","abstract":"Genome-wide association study of bullous pemphigoid in Germans, using 446 BP patients and 433 age- and sex- matched controls. 6 SNPs in the HLA locus were found to be of genome-wide significance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-21T12:13:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004628","title":"scRNASeq_Pilot","description":"These QQ pilot studies will test the effect of tissue storage on samples, with the aim of identifying the best sample storage method for QQ studies that aim to collect samples from 5 UK hospitals..","abstract":"These QQ pilot studies will test the effect of tissue storage on samples, with the aim of identifying the best sample storage method for QQ studies that aim to collect samples from 5 UK hospitals. \nTo explore the effect of tissue storage on gut biopsies (n=3 for cryopreservation and n=3 for snap-freezing and nuclear isolation) and the effect of 4oC storage on blood (n=3 for T24 and T48). We will also test the effect of 2 inhibitors on gut cell viability (n=3 biopsies) in combination.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004629","title":"Hepatitis B virus integrations promote local and distant oncogenic driver alterations in hepatocarcinogenesis","description":"Infection by Hepatitis B Virus (HBV) is the main risk factor for Hepatocellular Carcinoma (HCC) worldwide. HBV can directly drive carcinogenesis through integrations in human genome. This integrative analysis of a French cohort of 190 patients mainly coming from Europe and Africa provides a deep characterization of HBV integrations, in relation with viral and host genomics and clinical features. Clonal HBV integrations directly contribute to HCC development through alterations of cancer driver genes, either at distance when co-localizing with copy number alterations, either locally through viral Enhancers. Together, this analysis gives new insights on HBV-associated driver mechanisms involved in hepato-carcinogenesis.","abstract":"Infection by Hepatitis B Virus (HBV) is the main risk factor for Hepatocellular Carcinoma (HCC) worldwide. HBV can directly drive carcinogenesis through integrations in human genome. This integrative analysis of a French cohort of 190 patients mainly coming from Europe and Africa provides a deep characterization of HBV integrations, in relation with viral and host genomics and clinical features. Clonal HBV integrations directly contribute to HCC development through alterations of cancer driver genes, either at distance when co-localizing with copy number alterations, either locally through viral Enhancers. Together, this analysis gives new insights on HBV-associated driver mechanisms involved in hepato-carcinogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-24T09:57:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004630","title":"Targeted sequencing of breast cancer susceptibility genes for 1,995 Japanese breast cancer patients","description":"In this study, we investigated pathogenic germline variants in 11 genes implicated in hereditary breast cancer, including BRCA1, BRCA2, TP53, PTEN, CDH1, STK11, NF1, PALB2, ATM, CHEK2, NBN1, in a total of 1,995 unselected Japanese women with breast cancer using targeted-capture sequencing of pooled DNA (n = 106).","abstract":"In this study, we investigated pathogenic germline variants in 11 genes implicated in hereditary breast cancer, including BRCA1, BRCA2, TP53, PTEN, CDH1, STK11, NF1, PALB2, ATM, CHEK2, NBN1, in a total of 1,995 unselected Japanese women with breast cancer using targeted-capture sequencing of pooled DNA (n = 106).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-24T11:31:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004631","title":"Multi_omics_analysis_of_LCM_samples___DNA","description":"We aim to set up a multi-omics LCM pipeline to study transcritome and genome from the same biposy section across tumor and/or normal tissues. RNA and DNA was extracted from Lazer capture microdisection tissues and gDNA libraries were perpared with current standard LCM protocl. Libraies are pooled to be sequenced.","abstract":"In this study we aim to study genome and transcriptom from the same LCM section across tumor and normal tissues.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004632","title":"Mutational landscape of eccrine porocarcinoma (sweat gland tumour)","description":"Eccrine porocarcinoma (EP) is the most common form of sweat gland malignancy. The aetiology of EP is largely unknown.\nThe current lack of data on somatic mutation patterns in EP hampers the development of effective therapies.\nWe performed whole-exome sequencing in a well-characterized sample of 14 matched EP tumour/healthy surrounding tissue samples. Mutational profiling revealed a high overall median mutation rate. This was attributed to signatures of mutational processes related to ultraviolet (UV) exposure, APOBEC enzyme dysregulation, and defective homologous double-strand break repair. All of these processes cause genomic instability and are implicated in carcinogenesis. The analyses revealed alterations in the cancer driver genes and in crucial oncogenic pathways.","abstract":"Eccrine porocarcinoma (EP) is the most common form of sweat gland malignancy. The aetiology of EP is largely unknown.\nThe current lack of data on somatic mutation patterns in EP hampers the development of effective therapies.\nWe performed whole-exome sequencing in a well-characterized sample of 14 matched EP tumour/healthy surrounding tissue samples. Mutational profiling revealed a high overall median mutation rate. This was attributed to signatures of mutational processes related to ultraviolet (UV) exposure, APOBEC enzyme dysregulation, and defective homologous double-strand break repair. All of these processes cause genomic instability and are implicated in carcinogenesis. The analyses revealed alterations in the cancer driver genes and in crucial oncogenic pathways.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-24T15:56:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004633","title":"RNA-seq data of HGG PDOX study","description":null,"abstract":"We established 21 patient-derived pHGG orthotopic xenograft (PDOX) models and 8 matched cell lines from diverse pHGG subgroups. Models recapitulated histopathology, DNA methylation signatures, mutations and gene expression patterns of the patient tumors from which they were derived, and included rare subgroups not well-represented by existing models. We also included 6 DIPG cell lines generously shared by Dr. Michelle Monje (Stanford University).  An online interactive data portal is available to explore associated detailed molecular characterization and HTS chemical sensitivity data.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-24T22:25:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004634","title":"WES data of HGG PDOX study","description":null,"abstract":"We established 21 patient-derived pHGG orthotopic xenograft (PDOX) models and 8 matched cell lines from diverse pHGG subgroups. Models recapitulated histopathology, DNA methylation signatures, mutations and gene expression patterns of the patient tumors from which they were derived, and included rare subgroups not well-represented by existing models. We also included 6 DIPG cell lines generously shared by Dr. Michelle Monje (Stanford University).  An online interactive data portal is available to explore associated detailed molecular characterization and HTS chemical sensitivity data.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004635","title":"WGS data of HGG PDOX study","description":null,"abstract":"We established 21 patient-derived pHGG orthotopic xenograft (PDOX) models and 8 matched cell lines from diverse pHGG subgroups. Models recapitulated histopathology, DNA methylation signatures, mutations and gene expression patterns of the patient tumors from which they were derived, and included rare subgroups not well-represented by existing models. We also included 6 DIPG cell lines generously shared by Dr. Michelle Monje (Stanford University).  An online interactive data portal is available to explore associated detailed molecular characterization and HTS chemical sensitivity data.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004636","title":"Detection of ctDNA in Plasma of Patients with Clinically Localised Prostate Cancer is Associated with Rapid Disease Progression","description":"Purpose: DNA originating from degenerate tumour cells can be detected in the circulation in many tumour types, where it can be used as a marker of disease burden as well as to monitor treatment response. Although circulating tumour DNA (ctDNA) measurement has prognostic/predictive value in metastatic prostate cancer, its utility in localised disease is unknown.\nPatients and Methods: We performed whole genome sequencing of tumour-normal pairs in eight patients with clinically localised disease undergoing prostatectomy, identifying high confidence genomic aberrations. A bespoke DNA capture and amplification panel against the highest prevalence, highest confidence aberrations for each individual was designed and used to interrogate ctDNA isolated from plasma prospectively obtained pre- and post- (24 hours and 6 weeks) surgery. In a separate cohort (n=189) we identified the presence of ctDNA TP53 mutations in pre-operative plasma in a retrospective cohort, and determined its association with biochemical- and metastasis-free survival.\nResults: Tumour variants in ctDNA were positively identified pre-treatment in two of eight patients, which in both cases remained detectable postoperatively. Patients with tumour variants in ctDNA had extremely rapid disease recurrence and progression compared to those where variants could not be detected. In terms of aberrations targeted, single nucleotide and structural variants outperformed indels and copy number aberrations. Detection of ctDNA TP53 mutations was associated with a significantly shorter metastasis-free survival (6.2 vs. 9.5 years (HR 2.4; 95% CIs 1.2-4.8, p = 0.014)). Conclusions: CtDNA is uncommonly detected in localised prostate cancer but its presence portends more rapidly progressive disease.","abstract":"Purpose: DNA originating from degenerate tumour cells can be detected in the circulation in many tumour types, where it can be used as a marker of disease burden as well as to monitor treatment response. Although circulating tumour DNA (ctDNA) measurement has prognostic/predictive value in metastatic prostate cancer, its utility in localised disease is unknown.\nPatients and Methods: We performed whole genome sequencing of tumour-normal pairs in eight patients with clinically localised disease undergoing prostatectomy, identifying high confidence genomic aberrations. A bespoke DNA capture and amplification panel against the highest prevalence, highest confidence aberrations for each individual was designed and used to interrogate ctDNA isolated from plasma prospectively obtained pre- and post- (24 hours and 6 weeks) surgery. In a separate cohort (n=189) we identified the presence of ctDNA TP53 mutations in pre-operative plasma in a retrospective cohort, and determined its association with biochemical- and metastasis-free survival.\nResults: Tumour variants in ctDNA were positively identified pre-treatment in two of eight patients, which in both cases remained detectable postoperatively. Patients with tumour variants in ctDNA had extremely rapid disease recurrence and progression compared to those where variants could not be detected. In terms of aberrations targeted, single nucleotide and structural variants outperformed indels and copy number aberrations. Detection of ctDNA TP53 mutations was associated with a significantly shorter metastasis-free survival (6.2 vs. 9.5 years (HR 2.4; 95% CIs 1.2-4.8, p = 0.014)). Conclusions: CtDNA is uncommonly detected in localised prostate cancer but its presence portends more rapidly progressive disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-25T11:04:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004637","title":"Paediatric_and_adult_nasal_scRNAseq_COVID19","description":"Transcriptomic profiling of patient matched normal and CIS samples at the single-cell level.\n\nLung cancer kills more men and women than any other cancer. Smoking rates are decreasing, however given the rising trend of smoking in the Far East, India and Africa, this is unlikely to change. We remain convinced that to improve lung cancer survival we must detect or intervene early. The most common subtype of lung cancer in the UK is lung squamous cell carcinoma (LUSC), constituting 43% of lung cancer in England and Wales. LUSC develops through a progression from normal epithelium to low-grade lesions and then to carcinoma in situ (CIS, high-grade lesions), before progressing to invasive cancer.\nCancers are thought to develop from an area of epithelium equally exposed to toxins producing a ‘field of injury’. Our data demonstrates that the traditional understanding of ‘field of injury’ is flawed. We show that the airway as a whole can reverse genetic damage either through clonal expansion of less mutated cells or deletion of more mutated cells. To further define the ‘field of injury’ model in diseased airway we aim to analyse the transcriptional landscape of patient matched normal and CIS samples at the single-cell level. This will allow us to delineate specific cell subtype changes and key gene regulatory networks that will assist in our understanding of the progression of LUSC. Our findings could also develop a successful biomarker-driven early detection lung cancer programme. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Transcriptomic profiling of patient matched normal and CIS samples at the single-cell level.\n\nLung cancer kills more men and women than any other cancer. Smoking rates are decreasing, however given the rising trend of smoking in the Far East, India and Africa, this is unlikely to change. We remain convinced that to improve lung cancer survival we must detect or intervene early. The most common subtype of lung cancer in the UK is lung squamous cell carcinoma (LUSC), constituting 43% of lung cancer in England and Wales. LUSC develops through a progression from normal epithelium to low-grade lesions and then to carcinoma in situ (CIS, high-grade lesions), before progressing to invasive cancer.\nCancers are thought to develop from an area of epithelium equally exposed to toxins producing a ‘field of injury’. Our data demonstrates that the traditional understanding of ‘field of injury’ is flawed. We show that the airway as a whole can reverse genetic damage either through clonal expansion of less mutated cells or deletion of more mutated cells. To further define the ‘field of injury’ model in diseased airway we aim to analyse the transcriptional landscape of patient matched normal and CIS samples at the single-cell level. This will allow us to delineate specific cell subtype changes and key gene regulatory networks that will assist in our understanding of the progression of LUSC. Our findings could also develop a successful biomarker-driven early detection lung cancer programme. \n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004638","title":"Molecular classification improves risk assessment in adult B-lineage ALL: Patients on the international UKALLXII-ECOG2993 trial.","description":"Acute lymphoblastic leukemia (ALL) in adults is a rare disease with outcomes that remain significantly inferior to those of children with ALL. While  genomic classification of pediatric B-lineage ALL (B-ALL) has led to improved risk assignment and therapeutic paradigms, similar advances in adults have been lacking. The international UKALLXII/E2993 (NCT00002514) trial accrued over 2000 adult (17-64 years old) patients over 13 years, including 1229 BCR/ABL negative B-ALLs. While 93% of B-ALL achieved a remission, 41% relapsed at a median time of 13 months (Range) and overall survival (OS) at 5 years was 42% (CI). Older age and higher white blood cell (WBC) count at presentation negatively affected OS. Patients with a sibling donor assigned to allogeneic transplantation had superior OS compared to patients without donor. Randomization of patients without a donor showed an advantage of chemotherapy over autologous transplantation in first remission. Transcriptome sequencing of 94% of E2993 patients enabled genomic subtyping. We found that one-third of patients belonged to favorable genotypes (DUX4-rearranged, ETV6-RUNX1, TCF3-PBX1, PAX5 P80R, high hyperdiploidy). Of 63.4% of patients classified as high-risk based age and WBC count at diagnosis, almost 40% harbored subtype-defining genetic associations associated with favorable- or intermediate outcomes. These patients did significantly better than expected from their protocol-defined risk assignment. Our data in a large adult B-ALL cohort treated on a single international trial show the important prognostic value of genomic analysis and the potential benefit for many of the novel genotypes.","abstract":"Acute lymphoblastic leukemia (ALL) in adults is a rare disease with outcomes that remain significantly inferior to those of children with ALL. While  genomic classification of pediatric B-lineage ALL (B-ALL) has led to improved risk assignment and therapeutic paradigms, similar advances in adults have been lacking. The international UKALLXII/E2993 (NCT00002514) trial accrued over 2000 adult (17-64 years old) patients over 13 years, including 1229 BCR/ABL negative B-ALLs. While 93% of B-ALL achieved a remission, 41% relapsed at a median time of 13 months (Range) and overall survival (OS) at 5 years was 42% (CI). Older age and higher white blood cell (WBC) count at presentation negatively affected OS. Patients with a sibling donor assigned to allogeneic transplantation had superior OS compared to patients without donor. Randomization of patients without a donor showed an advantage of chemotherapy over autologous transplantation in first remission. Transcriptome sequencing of 94% of E2993 patients enabled genomic subtyping. We found that one-third of patients belonged to favorable genotypes (DUX4-rearranged, ETV6-RUNX1, TCF3-PBX1, PAX5 P80R, high hyperdiploidy). Of 63.4% of patients classified as high-risk based age and WBC count at diagnosis, almost 40% harbored subtype-defining genetic associations associated with favorable- or intermediate outcomes. These patients did significantly better than expected from their protocol-defined risk assignment. Our data in a large adult B-ALL cohort treated on a single international trial show the important prognostic value of genomic analysis and the potential benefit for many of the novel genotypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-25T20:34:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004639","title":"Population Genomics of Native Americans from Andes and Amazon","description":null,"abstract":"Using genome-wide information of Native Americans from Andes and Amazon we addressed questions about : the Andes-Amazon dichotomy, the Andean homogenization and how cultural and socioeconomic interactions revealed by archaeology were accompanied by gene flow, specifically in northern Peru. Moreover, this demographic history allowed for cases of positive natural selection in the high and arid Andes vs. the low Amazon tropical forest","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-25T20:41:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004640","title":"The proliferative history shapes the DNA methylome of B-cell tumor and predicts clinical outcome","description":"Here, we provide access to CLL and DLBCL DNA methylation and gene expression data in the context of a systematic analysis of the DNA methylation variability in 1,595 samples of normal cell subpopulations and 14 tumor subtypes spanning the entire human B-cell lineage. This approach showed that differential methylation among tumor entities relates to differences in cellular origin and to de novo epigenetic alterations, which allowed us to build an accurate machine learning-based diagnostic algorithm. We identify extensive patient-specific methylation variability in silenced chromatin associated with the proliferative history of normal and neoplastic B cells. Mitotic activity generally leaves both hyper- and hypomethylation imprints, but some B-cell neoplasms preferentially gain or lose DNA methylation. Subsequently, we construct a DNA methylation-based mitotic clock called epiCMIT, whose lapse magnitude represents a strong independent prognostic variable in B-cell tumors and is associated with particular driver genetic alterations. Our findings reveal DNA methylation as a holistic tracer of B-cell tumor developmental history, with implications in the differential diagnosis and prediction of clinical outcome.","abstract":"Here, we provide access to CLL and DLBCL DNA methylation and gene expression data in the context of a systematic analysis of the DNA methylation variability in 1,595 samples of normal cell subpopulations and 14 tumor subtypes spanning the entire human B-cell lineage. This approach showed that differential methylation among tumor entities relates to differences in cellular origin and to de novo epigenetic alterations, which allowed us to build an accurate machine learning-based diagnostic algorithm. We identify extensive patient-specific methylation variability in silenced chromatin associated with the proliferative history of normal and neoplastic B cells. Mitotic activity generally leaves both hyper- and hypomethylation imprints, but some B-cell neoplasms preferentially gain or lose DNA methylation. Subsequently, we construct a DNA methylation-based mitotic clock called epiCMIT, whose lapse magnitude represents a strong independent prognostic variable in B-cell tumors and is associated with particular driver genetic alterations. Our findings reveal DNA methylation as a holistic tracer of B-cell tumor developmental history, with implications in the differential diagnosis and prediction of clinical outcome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-26T15:17:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004641","title":"Characterization of stromal tumor-infiltrating lymphocytes and genomic alterations in metastatic lobular breast cancer","description":null,"abstract":"Purpose\nInvasive lobular carcinoma (ILC) represents the second most common histological breast cancer subtype after invasive ductal carcinoma (IDC). While primary ILC has been extensively studied, metastatic ILC has been poorly characterized at the genomic and immune level. \nExperimental design\nWe retrospectively assembled the multi-centric EuroILC series of matched primary and metastatic samples from 94 patients with estrogen receptor (ER)-positive ILC. Stromal tumor infiltrating lymphocytes (sTIL) were assessed by experienced pathologists. Targeted sequencing and low pass whole genome sequencing were conducted to detect mutations and copy number aberrations (CNAs). We compared the frequencies of the alterations in EuroILC with those from patients with ER-positive metastatic ILC (n=135) and IDC (n=563) from MSK-IMPACT. \nResults\nLow sTIL levels were observed in ILC metastases, with higher levels in the mixed non-classic histology. Considering ILC metastases from EuroILC and MSK-IMPACT, we observed that &gt;50% of tumors harbor genomic alterations that have previously been associated with endocrine resistance. A matched primary/metastasis comparison in EuroILC revealed mutations (AKT1, ARID1A, ESR1, ERBB2 or NF1) and CNAs (PTEN or NF1 deletion, CYP19A1 amplification) associated with endocrine resistance that were private to the metastasis in 22% (7/32) and 19% (4/21) of patients, respectively. An increase in CDH1, ERBB2, FOXA1 and TBX3 mutations, in CDH1 deletions and a decrease in TP53 mutations was observed in ILC as compared to IDC metastases. \nConclusions\nILC metastases harbor genomic alterations that may potentially explain endocrine resistance in a large proportion of patients, and present genomic differences as compared to IDC metastases.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-26T15:38:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004642","title":"Genomewide detection of cytosine methylation by single molecule real-time sequencing","description":"5-methylcytosine (5mC) is an important type of epigenetic modification. In this study, we enhanced 5mC detection using SMRT sequencing by holistically analyzing kinetic signals of a DNA polymerase and sequence context for every base within a measurement window. We employed a convolutional neural network to train a methylation classification model. This methodology has provided a system for simultaneous genome-wide genetic and epigenetic analyses. ","abstract":"5-methylcytosine (5mC) is an important type of epigenetic modification. In this study, we enhanced 5mC detection using SMRT sequencing by holistically analyzing kinetic signals of a DNA polymerase and sequence context for every base within a measurement window. We employed a convolutional neural network to train a methylation classification model. This methodology has provided a system for simultaneous genome-wide genetic and epigenetic analyses. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-27T04:03:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004643","title":"Integrative analysis of metastatic uveal melanoma uncovers epigenomic rewiring in enhancers activating oncogenic drivers","description":null,"abstract":"Metastatic uveal melanoma (mUM) is a dismal disease which is poorly understood. Genomic studies in mUM focused on tumors with monosomy 3 (M3), an established marker predicting high metastasis risk in UM. We report a systems-level analysis on a cohort of 41 mUMs revealing a significant fraction of disomy 3 (D3) cases, presenting late-onset relapse. Integrative transcriptome and deep whole genome bisulfite sequencing uncovers that activation of salient oncogenic pathways in mUM subgroups is co-mediated by epigenetic alterations. CpG demethylation in gene regulatory regions, mostly active enhancers, correlates with upregulation of  MET ,  BCL2 ,  CD44,  and the RAS activators  RASGRP3  and  SOS1 mediating G α q/11   signaling in all mUMs. Specific methylome re-patterning in tumor subgroups indicates divergent routes towards metastasis, dysregulating different factors promoting stemness and cell migration in M3- and D3-mUM.  This resource provides  insights for understanding the UM metastatic setting and identifies potential therapeutic vulnerabilities.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004644","title":"NF1 is a predictor for personalized surgical approach to high-grade serous ovarian cancer","description":null,"abstract":"NF1 losses as a predictor for personalized surgical approach to high-grade serous ovarian cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004645","title":"Comprehensive molecular characteriazation of pulmonary sarcomatoid carcinoma","description":null,"abstract":"Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung cancer with poor prognosis. Here we perform multi-omics analysis of PSC samples to reveal the molecular characteristics and provide new entry points for the treatment of PSC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004646","title":"RNA sequencing of follicular T cell lymphoma","description":null,"abstract":"RNA sequencing of follicular T cell lymphoma to identify novel fusion transcripts.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-31T14:58:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004647","title":"Analysis of transcriptomic profiles from affected and recovered muscle biopsies from children with reversible infantile respiratory chain deficiency.","description":"All patients carry mitochondrial mutation m.14674T&gt;C but not must also carry mutations in related genes such as TRMU and EARS2. Analysis compares muslce biopsies of affected patients to controls, a patient after recovery to themselves during the the disease phase, and compared patients with additional EARS2 mutations to patients without pathogenic EARS2 mutations.","abstract":"All patients carry mitochondrial mutation m.14674T&gt;C but not must also carry mutations in related genes such as TRMU and EARS2. Analysis compares muslce biopsies of affected patients to controls, a patient after recovery to themselves during the the disease phase, and compared patients with additional EARS2 mutations to patients without pathogenic EARS2 mutations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-31T20:20:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004648","title":"Molecular Tumor Board to Inform on Personalized Medicine for a Man with Advanced Prostate Cancer","description":"Purpose: Molecular profiling of cancer is increasingly common as part of routine care in oncology, and germline and somatic profiling may provide insights and actionable targets for men with metastatic prostate cancer. However, all reported cases are of deidentified individuals without full medical and genomic data available in the public domain.\n\nPatient and Methods: We present a case of whole genome tumor and germline sequencing in a patient with advanced prostate cancer, who has agreed to make his genomic and clinical data publicly available in an accompanying personal testimonial.\n\nResults: We describe an 84-year-old Caucasian male with a Gleason 10 oligometastastic hormone-sensitive prostate cancer. Whole-genome sequencing provided insights into his tumor’s underlying mutational processes and the development of an SPOP mutation. It also revealed an androgen-receptor dependency of his cancer which was reflected in his durable response to radiation and hormonal therapy. Potentially actionable genomic lesions in the tumor were identified through a personalized medicine approach for potential future therapy, but at the moment, he remains in remission, illustrating the hormonal sensitivity of his SPOP-driven prostate cancer. We also placed this patient in the context of a large prostate-cancer cohort from the PCAWG (Pan-cancer Analysis of Whole Genomes) group. In this comparison, the patient's cancer appears typical in terms of the number and type of somatic mutations, but it has a somewhat larger contribution from the mutational process associated with aging.\n\nConclusion: We combined the expertise of medical oncology and genomics approaches to develop a molecular tumor board to integrate the care and study of this patient, who continues to have an outstanding response to his combined modality treatment. This identifiable case potentially helps overcome barriers to clinical and genomic data sharing.","abstract":"Purpose: Molecular profiling of cancer is increasingly common as part of routine care in oncology, and germline and somatic profiling may provide insights and actionable targets for men with metastatic prostate cancer. However, all reported cases are of deidentified individuals without full medical and genomic data available in the public domain.\n\nPatient and Methods: We present a case of whole genome tumor and germline sequencing in a patient with advanced prostate cancer, who has agreed to make his genomic and clinical data publicly available in an accompanying personal testimonial.\n\nResults: We describe an 84-year-old Caucasian male with a Gleason 10 oligometastastic hormone-sensitive prostate cancer. Whole-genome sequencing provided insights into his tumor’s underlying mutational processes and the development of an SPOP mutation. It also revealed an androgen-receptor dependency of his cancer which was reflected in his durable response to radiation and hormonal therapy. Potentially actionable genomic lesions in the tumor were identified through a personalized medicine approach for potential future therapy, but at the moment, he remains in remission, illustrating the hormonal sensitivity of his SPOP-driven prostate cancer. We also placed this patient in the context of a large prostate-cancer cohort from the PCAWG (Pan-cancer Analysis of Whole Genomes) group. In this comparison, the patient's cancer appears typical in terms of the number and type of somatic mutations, but it has a somewhat larger contribution from the mutational process associated with aging.\n\nConclusion: We combined the expertise of medical oncology and genomics approaches to develop a molecular tumor board to integrate the care and study of this patient, who continues to have an outstanding response to his combined modality treatment. This identifiable case potentially helps overcome barriers to clinical and genomic data sharing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-08-31T22:57:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004649","title":"Targeted sequencing of Burkitt lymphoma tumour samples from the UK's Haematological Malignancy Research Network","description":"The UK’s Haematological Malignancy Research Network (www.HMRN.org) was established in 2004 to provide robust generalizable data to inform clinical practice and research.  HMRN is a collaboration between researchers in the Epidemiology &amp;amp; Statistics Group (ECSG) at the University of York, a unified Clinical Network operating across 14 hospitals, and an integrated Haematological Malignancy Diagnostic Service (HMDS) in Leeds. \n \nCovering a population of around 4 million, HMRN collects detailed information about all patients diagnosed with a haematological malignancy within the HMRN region, accruing around 2,400 new diagnoses each year. The population has a similar socio-demographic profile to the country as a whole, and HMRN’s maturing data present an increasingly valuable resource to address real questions of concern to haematologists, commissioners and health service researchers – locally, nationally and internationally.\n \nThis study forms part of a larger project employing targeted exome sequencing on tumour samples from patients diagnosed with a variety of both lymphoid and myeloid malignancies. The results for samples collected from 39 Burkitt lymphoma patients, diagnosed within HMRN from 2005 to 2012, are provided.","abstract":"The UK’s Haematological Malignancy Research Network (www.HMRN.org) was established in 2004 to provide robust generalizable data to inform clinical practice and research.  HMRN is a collaboration between researchers in the Epidemiology &amp;amp; Statistics Group (ECSG) at the University of York, a unified Clinical Network operating across 14 hospitals, and an integrated Haematological Malignancy Diagnostic Service (HMDS) in Leeds. \n \nCovering a population of around 4 million, HMRN collects detailed information about all patients diagnosed with a haematological malignancy within the HMRN region, accruing around 2,400 new diagnoses each year. The population has a similar socio-demographic profile to the country as a whole, and HMRN’s maturing data present an increasingly valuable resource to address real questions of concern to haematologists, commissioners and health service researchers – locally, nationally and internationally.\n \nThis study forms part of a larger project employing targeted exome sequencing on tumour samples from patients diagnosed with a variety of both lymphoid and myeloid malignancies. The results for samples collected from 39 Burkitt lymphoma patients, diagnosed within HMRN from 2005 to 2012, are provided.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-01T12:53:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004650","title":"Genome-wide information of Peruvian Native American","description":null,"abstract":"Peruvian Native American individuals were genotyped as part of the Peruvian Genome Project (PGP). This data was used to infer population structure, demographic history and natural selection. We addressed question about gene flow across the Andes and Natural Selection in Andes and Amazon","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-02T00:20:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004651","title":"Cerebrospinal fluid circulating tumour DNA allows the  characterisation and monitoring of medulloblastoma","description":"The molecular characterisation of medulloblastoma, the most common paediatric brain tumour, is crucial for the correct management and treatment of this heterogenous disease.\nIn this study we show that CSF ctDNA allows the molecular characterisation and monitoring of medulloblastoma. This can ultimately facilitate the clinical management of medulloblastoma patients.","abstract":"The molecular characterisation of medulloblastoma, the most common paediatric brain tumour, is crucial for the correct management and treatment of this heterogenous disease.\nIn this study we show that CSF ctDNA allows the molecular characterisation and monitoring of medulloblastoma. This can ultimately facilitate the clinical management of medulloblastoma patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-02T09:50:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004652","title":"Understanding_T_cell_Response_to_Biological_therapeutics","description":"This study aims to unveil causal genes and biological pathways involved in immune cell response to the most frequently prescribed biologic drugs to treat IBD, i.e. anti-TNF, anti-IL23/12 and JAK2 inhibitors\n\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"This study aims to unveil causal genes and biological pathways involved in immune cell response to the most frequently prescribed biologic drugs to treat IBD, i.e. anti-TNF, anti-IL23/12 and JAK2 inhibitors. We will establish a series of genome-wide (GW)-CRISPR knockout screens in primary CD4+ or CD8+ T cells to investigate cell response to anti-TNF, anti-IL23/12 and JAK2 inhibitors (8 CRISPR-screen groups). T cells will be co-cultured with autologous macrophages and exposed to drugs or vehicle. These cells will be sorted according to proliferation levels, gRNAs sequenced and analysed. These experiments will identify, in an unbiased way, which genes contribute to immunosuppressive effects of each drug in two cell-contexts. \nGW-CRISPR screens will be followed by prioritization of 20 response genes with the strongest enrichment scores. T cells will be isolated and their genome edited by CRISPR/Cas9 to induce insertions/deletions on response genes. Cells will be exposed to drugs for 24 hours and analysed using single cell RNA-sequencing to obtain a high dimensional phenotype. These experiments will identify biological pathways associated with response to these biological drugs. In addition, these data will reveal potential drug targets and/or combination therapies to minimise the burden of lack of drug response in IBD patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004653","title":"Single nucleus and in situ RNA sequencing reveals cell topographies in the human pancreas","description":"Molecular evidence of cellular heterogeneity in the human exocrine pancreas has not been established, due to the local concentration of hydrolytic enzymes that can rapidly degrade cells and RNA upon resection. Here we innovated single-nucleus RNA sequencing protocols, and profiled more than 120,000 cells from adult and neonatal human donors to create the first comprehensive atlas of human pancreas cells, including epithelial and non-epithelial constituents. Adult and neonatal pancreata shared common features, including the presence of previously undetected acinar subtypes, but also showed marked differences in the composition of the endocrine, endothelial, and immune compartments. Spatial cartography, including cell proximity mapping through in situ sequencing, revealed dynamic developmental cell topographies in the endocrine and exocrine pancreas. Our human pancreas cell atlas can be interrogated to understand pancreatic cell biology, and provides a crucial reference set for future comparisons with diseased tissue samples to map the cellular foundations of pancreatic diseases.","abstract":"Molecular evidence of cellular heterogeneity in the human exocrine pancreas has not been established, due to the local concentration of hydrolytic enzymes that can rapidly degrade cells and RNA upon resection. Here we innovated single-nucleus RNA sequencing protocols, and profiled more than 120,000 cells from adult and neonatal human donors to create the first comprehensive atlas of human pancreas cells, including epithelial and non-epithelial constituents. Adult and neonatal pancreata shared common features, including the presence of previously undetected acinar subtypes, but also showed marked differences in the composition of the endocrine, endothelial, and immune compartments. Spatial cartography, including cell proximity mapping through in situ sequencing, revealed dynamic developmental cell topographies in the endocrine and exocrine pancreas. Our human pancreas cell atlas can be interrogated to understand pancreatic cell biology, and provides a crucial reference set for future comparisons with diseased tissue samples to map the cellular foundations of pancreatic diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-02T18:12:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004654","title":"Exome sequencing of DNA from pituitary neuroendocrine tumor (PitNET) and germline DNA from the same patient","description":"The goal of the project is to study tumor - normal DNA pairs from the PitNET patients. Total of 15 PitNET patients were recruited for the study to investigate sometic changes in the tumor compared to normal tissue. Illumina technology were used for sequencing and two data analysis pipelines employed for data analysis. Recurrent somatic variations were investigated and genomic disruption analysis from exome sequencing data attempted.","abstract":"The goal of the project is to study tumor - normal DNA pairs from the PitNET patients. Total of 15 PitNET patients were recruited for the study to investigate sometic changes in the tumor compared to normal tissue. Illumina technology were used for sequencing and two data analysis pipelines employed for data analysis. Recurrent somatic variations were investigated and genomic disruption analysis from exome sequencing data attempted.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-03T11:40:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004655","title":"An Integrated Approach to Patient Stratification and Therapy Selection in Acute Myeloid Leukemia","description":null,"abstract":"As more clinically-relevant genomic features of myeloid malignancies are revealed, it has become clear that targeted clinical genetic testing is inadequate for risk stratification. Here, we developed and validated a clinical transcriptome-based assay for stratification of acute myeloid leukemia (AML). Comparison of RNA-Seq to whole genome and exome sequencing revealed that as a standalone assay, RNA-Seq offered the greatest diagnostic return, enabling identification of expressed gene fusions, single nucleotide and short insertion/deletion variants, and whole-transcriptome expression information. Expression data were used to develop a novel risk score which, when combined with molecular risk guidelines, allowed for the re-stratification of 22.1 to 25.3% of AML patients from three independent cohorts into correct risk groups. Within the adverse-risk subgroup, we identified a subset of patients characterized by dysregulated integrin signaling and RUNX1 or TP53 mutation. We show that these patients may benefit from therapy with inhibitors of focal adhesion kinase (PTK2), demonstrating additional utility of transcriptome-based testing for therapy selection in myeloid malignancy.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-04T18:39:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004656","title":"Single cell RNA-sequencing of GSCs and GBM tumours","description":"Characterization of glioblastoma tumors and glioblastoma stem cell (GSCs) lines with single cell or single nuclei RNA-sequencing.","abstract":"Characterization of glioblastoma tumors and glioblastoma stem cell (GSCs) lines with single cell or single nuclei RNA-sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-05T17:52:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004657","title":"Tissue-specific cell-free DNA degradation quantifies circulating tumor DNA burden","description":"Profiling of circulating tumor DNA (ctDNA) may offer a non-invasive approach to monitor disease progression. Here, we developed a quantitative method, exploiting local tissue-specific cell-free DNA (cfDNA) degradation patterns, that accurately estimates ctDNA burden independent of genomic aberrations. Nucleosome-dependent cfDNA degradation at promoters and first exon-intron junctions was strongly associated with differential transcriptional activity in tumors and blood. A quantitative model, based on just 6 regulatory regions, could accurately predict ctDNA levels in colorectal cancer patients. Strikingly, a model restricted to blood-specific regulatory regions could predict ctDNA levels across both colorectal and breast cancer patients.","abstract":"Profiling of circulating tumor DNA (ctDNA) may offer a non-invasive approach to monitor disease progression. Here, we developed a quantitative method, exploiting local tissue-specific cell-free DNA (cfDNA) degradation patterns, that accurately estimates ctDNA burden independent of genomic aberrations. Nucleosome-dependent cfDNA degradation at promoters and first exon-intron junctions was strongly associated with differential transcriptional activity in tumors and blood. A quantitative model, based on just 6 regulatory regions, could accurately predict ctDNA levels in colorectal cancer patients. Strikingly, a model restricted to blood-specific regulatory regions could predict ctDNA levels across both colorectal and breast cancer patients.","study_type":"Other","pubmed_ids":[33850132],"external_links":null,"is_released":true,"released_date":"2020-09-08T03:44:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004658","title":"WGS from 10 malignant peripheral nerve sheat tumors (MPNST)","description":null,"abstract":"Malignant peripheral nerve sheath tumors (MPNST) are rare soft-tissue sarcomas with bad prognosis and limited treatment options. About half of the MPNST arise in Neurofibromatosis Type 1 (NF1) patients, while the other half is of sporadic origin. In order to better understand the biology of these tumors, we have sequenced the whole genome of 10 of them, the largest publicly available collection so far. This work is part of a larger project involving the creation of a preclinical platform for MPNSTs with mice PDOX and new cell-lines derived from these same tumors.","study_type":"Cancer Genomics","pubmed_ids":[25810463],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004659","title":"Molecular and functional profiling of plasmablastic lymphoma","description":"Plasmablastic lymphoma (PBL) represents a rare and aggressive lymphoma subtype frequently associated with immunosuppression. Clinically, patients with PBL are characterized by poor outcome. The current understanding of the molecular pathogenesis is limited. A hallmark of PBL represents its plasmacytic differentiation with loss of B-cell markers and, in 60% of cases, its association with Epstein-Barr virus (EBV). Roughly 50% of PBLs harbor a MYC translocation. Here, we provide a comprehensive integrated genomic analysis using whole exome sequencing (WES) and genome-wide copy number determination in a large cohort of 96 primary PBL samples. We identify alterations activating the RAS-RAF, JAK-STAT, and NOTCH pathways as well as frequent high-level amplifications in MCL1 and IRF4. The functional impact of these alterations is assessed using an unbiased shRNA screen in a PBL model. These analyses identify the IRF4 and JAK-STAT pathways as promising molecular targets to improve outcome of PBL patients.","abstract":"Plasmablastic lymphoma (PBL) represents a rare and aggressive lymphoma subtype frequently associated with immunosuppression. Clinically, patients with PBL are characterized by poor outcome. The current understanding of the molecular pathogenesis is limited. A hallmark of PBL represents its plasmacytic differentiation with loss of B-cell markers and, in 60% of cases, its association with Epstein-Barr virus (EBV). Roughly 50% of PBLs harbor a MYC translocation. Here, we provide a comprehensive integrated genomic analysis using whole exome sequencing (WES) and genome-wide copy number determination in a large cohort of 96 primary PBL samples. We identify alterations activating the RAS-RAF, JAK-STAT, and NOTCH pathways as well as frequent high-level amplifications in MCL1 and IRF4. The functional impact of these alterations is assessed using an unbiased shRNA screen in a PBL model. These analyses identify the IRF4 and JAK-STAT pathways as promising molecular targets to improve outcome of PBL patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-09T12:41:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004660","title":"Aggressive PDACs show hypomethylation of repetitive elements and the execution of an intrinsic IFN program linked to a ductal cell-of-origin","description":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer embedded in an e , we FACS-purified epithelial cells from PDAC and healthy human pancreas and performed genome-wide transcriptome and DNA methylome analyses. Clustering based on DNA methylation revealed two distinct groups of PDAC with different methylation levels at genomic regions encoding repeat elements. Methylationlow tumors showed higher expression of endogenous retroviral (ERV) transcripts and a strong engagement of the dsRNA sensing machinery. This results in the cell intrinsic activation of an interferon response signature (IFNsign), leading to the reprogramming of stromal cells towards a pro-tumorigenic microenvironment and poor patient outcome. Methylationlow/IFNsignhigh and Methylationhigh/IFNsignlow PDAC cells harboured distinct lineage traits specific for normal ductal or acinar pancreatic epithelial cells at the methylation and transcriptional level. Moreover, ductal-cell-derived KrasG12D/Trp53-/- mutant mouse PDACs showed higher expression of IFNsign compared to tumors initiated by the same drivers in acinar cells. Collectively, our data point to two distinct origins and etiology of human PDACs, with the aggressive Methylationlow/IFNsignhigh tumor subtype potentially targetable by agents blocking cell intrinsic IFN-signaling. (H015)","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-09T14:41:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004661","title":"scRNA-seq of patient-derived PDAC organoids","description":"We derived PDAC organoids from primary tumors of 18 patients, together with two matched samples from liver metastases. By single-cell RNA sequencing, we show that PDAC organoids consist of ductal cells with patient-specific expression of several gene groups, including genes which encode cell surface proteins. We report ‘classical’ and ‘basal-like’ cells coexisting within single primary tumors or metastases, with greater intratumor subtype heterogeneity linked to higher tumor grade. Single-cell transcriptome analysis of PDAC organoids and primary PDAC identified distinct tumor cell states shared across patients, including a cycling progenitor cell state and a differentiated secretory state. We show that these cell states are connected by a differentiation hierarchy, with ‘classical’ subtype cells concentrated at the endpoint of this hierarchy.","abstract":"We derived PDAC organoids from primary tumors of 18 patients, together with two matched samples from liver metastases. By single-cell RNA sequencing, we show that PDAC organoids consist of ductal cells with patient-specific expression of several gene groups, including genes which encode cell surface proteins. We report ‘classical’ and ‘basal-like’ cells coexisting within single primary tumors or metastases, with greater intratumor subtype heterogeneity linked to higher tumor grade. Single-cell transcriptome analysis of PDAC organoids and primary PDAC identified distinct tumor cell states shared across patients, including a cycling progenitor cell state and a differentiated secretory state. We show that these cell states are connected by a differentiation hierarchy, with ‘classical’ subtype cells concentrated at the endpoint of this hierarchy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-09T20:43:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004662","title":"Chromothripsis in human breast cancer (HIPO K26K/H017/A017)","description":"Chromothripsis is a form of genome instability, by which a presumably single catastrophic event generates extensive  genomic rearrangements of one or a few chromosome(s). Widely assumed to be an early event in tumor development, this\nphenomenon plays a prominent role in tumor onset. We analyzed chromothripsis in 252 human breast cancers from two patient cohorts (149 metastatic breast cancers, 63 untreated primary tumors, 29 local relapses, 11 longitudinal pairs) using whole-genome and whole-exome sequencing. We showed that chromothripsis affects a substantial proportion of human breast cancers, with a prevalence over 60% in a cohort of metastatic cases and 25% in a cohort comprising predominantly luminal breast cancers (cohorts from HIPO K26K and H017 and A017). In the vast majority of cases, multiple chromosomes per tumor are affected, with most chromothriptic events on chromosomes 11 and 17 including, among other significantly altered drivers, CCND1, ERBB2, CDK12 and BRCA1. Importantly, chromothripsis generates recurrent fusions that drive tumor development. Chromothripsis-related rearrangements are linked with univocal mutational signatures, with clusters of point mutations due to kataegis in close proximity to the genomic breakpoints, and with the activation of specific signaling pathways. Analysis of the temporal order of events in tumors with and without chromothripsis as well as longitudinal analysis of chromothriptic patterns in tumor pairs revealed important insights on the role of chromothriptic chromosomes in tumor evolution.","abstract":"Chromothripsis is a form of genome instability, by which a presumably single catastrophic event generates extensive  genomic rearrangements of one or a few chromosome(s). Widely assumed to be an early event in tumor development, this\nphenomenon plays a prominent role in tumor onset. We analyzed chromothripsis in 252 human breast cancers from two patient cohorts (149 metastatic breast cancers, 63 untreated primary tumors, 29 local relapses, 11 longitudinal pairs) using whole-genome and whole-exome sequencing. We showed that chromothripsis affects a substantial proportion of human breast cancers, with a prevalence over 60% in a cohort of metastatic cases and 25% in a cohort comprising predominantly luminal breast cancers (cohorts from HIPO K26K and H017 and A017). In the vast majority of cases, multiple chromosomes per tumor are affected, with most chromothriptic events on chromosomes 11 and 17 including, among other significantly altered drivers, CCND1, ERBB2, CDK12 and BRCA1. Importantly, chromothripsis generates recurrent fusions that drive tumor development. Chromothripsis-related rearrangements are linked with univocal mutational signatures, with clusters of point mutations due to kataegis in close proximity to the genomic breakpoints, and with the activation of specific signaling pathways. Analysis of the temporal order of events in tumors with and without chromothripsis as well as longitudinal analysis of chromothriptic patterns in tumor pairs revealed important insights on the role of chromothriptic chromosomes in tumor evolution.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-11T12:57:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004663","title":"Targeting AXL Kinase Uniquely Sensitizes Therapy-Insensitive Leukemic Stem and Progenitor Cells to Venetoclax Treatment in Acute Myeloid Leukemia","description":"The abundance of genetic abnormalities and phenotypic heterogeneities in AML pose significant challenges to developing improved treatments. Here we demonstrated that a key GAS6/AXL axis is highly activated in AML patient cells, particularly in leukemic stem cells. We developed a potent, selective AXL inhibitor that has excellent pharmaceutical properties and efficacy against preclinical patient-derived xenotransplantation models of AML. Importantly, inhibition of AXL sensitized AML stem/progenitor cells to venetoclax treatment, with strong synergistic effects in vitro and in vivo. Mechanistically, single-cell RNA-sequencing and functional validation studies uncovered that AXL inhibition or in combination with venetoclax potentially targets intrinsic metabolic vulnerabilities of AML stem/progenitor cells, which shows a distinct transcriptomic profile and inhibits mitochondrial oxidative phosphorylation. These findings have direct translational impact on the treatment of AML and other cancers with high AXL activity.","abstract":"The abundance of genetic abnormalities and phenotypic heterogeneities in AML pose significant challenges to developing improved treatments. Here we demonstrated that a key GAS6/AXL axis is highly activated in AML patient cells, particularly in leukemic stem cells. We developed a potent, selective AXL inhibitor that has excellent pharmaceutical properties and efficacy against preclinical patient-derived xenotransplantation models of AML. Importantly, inhibition of AXL sensitized AML stem/progenitor cells to venetoclax treatment, with strong synergistic effects in vitro and in vivo. Mechanistically, single-cell RNA-sequencing and functional validation studies uncovered that AXL inhibition or in combination with venetoclax potentially targets intrinsic metabolic vulnerabilities of AML stem/progenitor cells, which shows a distinct transcriptomic profile and inhibits mitochondrial oxidative phosphorylation. These findings have direct translational impact on the treatment of AML and other cancers with high AXL activity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-13T02:38:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004664","title":"Tumour gene expression signature in primary melanoma predicts long-term outcomes: A prospective multicentre study","description":"Adjuvant systemic therapies are now routinely used following resection of stage III melanoma, however accurate prognostic information is needed to better stratify patients. We used differential expression analyses of primary tumours from 204 RNA-sequenced melanomas within a large adjuvant trial, identifying a 121 metastasis-associated gene signature. This signature strongly associated with progression-free (HR=1.63, p=5.24x10-5) and overall survival (HR=1.61, p=1.67x10-4), and validated in 177 regional lymph nodes metastasis as well as two externally ascertained datasets. The machine learning classification models trained using the signature genes performed significantly better in predicting metastases than models trained with clinical covariates (pAUROC=0.02), or published prognostic signatures. The signature score negatively correlated with measures of immune cell infiltration (ρ=-0.75, p&lt;2.2x10-16), with a higher score representing reduced lymphocyte infiltration and a higher 5-year risk of death in stage II melanoma. Our expression signature identifies melanoma patients at higher risk of metastases and warrants further evaluation in adjuvant clinical trials.","abstract":"Adjuvant systemic therapies are now routinely used following resection of stage III melanoma, however accurate prognostic information is needed to better stratify patients. We used differential expression analyses of primary tumours from 204 RNA-sequenced melanomas within a large adjuvant trial, identifying a 121 metastasis-associated gene signature. This signature strongly associated with progression-free (HR=1.63, p=5.24x10-5) and overall survival (HR=1.61, p=1.67x10-4), and validated in 177 regional lymph nodes metastasis as well as two externally ascertained datasets. The machine learning classification models trained using the signature genes performed significantly better in predicting metastases than models trained with clinical covariates (pAUROC=0.02), or published prognostic signatures. The signature score negatively correlated with measures of immune cell infiltration (ρ=-0.75, p&lt;2.2x10-16), with a higher score representing reduced lymphocyte infiltration and a higher 5-year risk of death in stage II melanoma. Our expression signature identifies melanoma patients at higher risk of metastases and warrants further evaluation in adjuvant clinical trials.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-14T09:19:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004665","title":"Human breast transcriptome analysis","description":"Obesity is a risk factor for the development of post-menopausal breast cancer and is associated with a worse breast cancer prognosis. Here we carried out transcriptome profiling on nontumorous breast tissue to define the molecular changes that occur related to excess body fat and adipose inflammation. A second goal was to determine if blood biomarkers reflect molecular changes in the breast. Increases in a variety of pathways linked to tumor development and progression were found. Moreover, increased expression of several drug targets including aromatase, the rate-limiting enzyme for estrogen biosynthesis, and PD-1 was observed. Various blood biomarkers that are associated with either elevated risk of breast cancer or worse prognosis were altered and correlated with molecular changes in the breast. Collectively, this study helps to explain both the link between obesity and breast cancer and the utility of blood biomarkers for determining risk and prognosis.","abstract":"Obesity is a risk factor for the development of post-menopausal breast cancer and is associated with a worse breast cancer prognosis. Here we carried out transcriptome profiling on nontumorous breast tissue to define the molecular changes that occur related to excess body fat and adipose inflammation. A second goal was to determine if blood biomarkers reflect molecular changes in the breast. Increases in a variety of pathways linked to tumor development and progression were found. Moreover, increased expression of several drug targets including aromatase, the rate-limiting enzyme for estrogen biosynthesis, and PD-1 was observed. Various blood biomarkers that are associated with either elevated risk of breast cancer or worse prognosis were altered and correlated with molecular changes in the breast. Collectively, this study helps to explain both the link between obesity and breast cancer and the utility of blood biomarkers for determining risk and prognosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-14T13:33:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004666","title":"Genomic analysis of patient-derived xenograft models reveals intratumor-heterogeneity in endometrial cancer and can predict tumor growth inhibition with talazoparib","description":"Background: Endometrial cancer (EC) is a major gynecological cancer with increasing incidence. It comprised of four molecular subtypes with differing etiology, prognoses, and response to chemotherapy. In the future, clinical trials testing new single agents or combination therapies will be targeted to the molecular subtype most likely to respond. Pre-clinical models that faithfully represent the molecular subtypes of EC are urgently needed, we sought to develop and characterize a panel of novel EC patient-derived xenograft (PDX) models.\n\nMethods: Here, we report whole exome or whole genome sequencing of 11 PDX models and the matched primary tumor. Analysis of multiple PDX lineages and passages was performed to study tumor heterogeneity across lineages and/or passages. Based on recent reports of frequent defects in the homologous recombination (HR) pathway in EC, we assessed mutational signatures and HR deficiency scores and correlated these with in vivo responses to the PARP inhibitor (PARPi) talazoparib in six PDXs representing the copy number high/p53-mutant and mismatch-repair deficient molecular subtypes of EC.\n\nResults: PDX models were successfully generated with similar histomorphology from all four molecular subtypes of EC and uterine carcinosarcomas. We also observed a wide range of inter-tumor and intra-tumor heterogeneity across different PDX lineages, however one arm of most PDX models recapitulated the molecular landscape of the primary tumor without major genomic drift. An in vivo response to talazoparib was detected in four copy number high models. Two models (carcinosarcomas) showed a response consistent with stable disease and two models (one copy number high serous EC and another carcinosarcoma) showed significant tumor growth inhibition, albeit one consistent with progressive disease, however all lacked the HR deficiency genomic signature. \n\nConclusions: EC PDX models represent the four molecular subtypes of disease and can capture intra-tumoral heterogeneity of the original primary tumor. PDXs of the copy number high molecular subtype showed sensitivity to PARPi, however, deeper and more durable responses will likely require combination of PARPi with other agents.","abstract":"Background: Endometrial cancer (EC) is a major gynecological cancer with increasing incidence. It comprised of four molecular subtypes with differing etiology, prognoses, and response to chemotherapy. In the future, clinical trials testing new single agents or combination therapies will be targeted to the molecular subtype most likely to respond. Pre-clinical models that faithfully represent the molecular subtypes of EC are urgently needed, we sought to develop and characterize a panel of novel EC patient-derived xenograft (PDX) models.\n\nMethods: Here, we report whole exome or whole genome sequencing of 11 PDX models and the matched primary tumor. Analysis of multiple PDX lineages and passages was performed to study tumor heterogeneity across lineages and/or passages. Based on recent reports of frequent defects in the homologous recombination (HR) pathway in EC, we assessed mutational signatures and HR deficiency scores and correlated these with in vivo responses to the PARP inhibitor (PARPi) talazoparib in six PDXs representing the copy number high/p53-mutant and mismatch-repair deficient molecular subtypes of EC.\n\nResults: PDX models were successfully generated with similar histomorphology from all four molecular subtypes of EC and uterine carcinosarcomas. We also observed a wide range of inter-tumor and intra-tumor heterogeneity across different PDX lineages, however one arm of most PDX models recapitulated the molecular landscape of the primary tumor without major genomic drift. An in vivo response to talazoparib was detected in four copy number high models. Two models (carcinosarcomas) showed a response consistent with stable disease and two models (one copy number high serous EC and another carcinosarcoma) showed significant tumor growth inhibition, albeit one consistent with progressive disease, however all lacked the HR deficiency genomic signature. \n\nConclusions: EC PDX models represent the four molecular subtypes of disease and can capture intra-tumoral heterogeneity of the original primary tumor. PDXs of the copy number high molecular subtype showed sensitivity to PARPi, however, deeper and more durable responses will likely require combination of PARPi with other agents.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-15T00:22:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004667","title":"AGENA_HO_after_hip_replacement","description":"Heterotopic ossification (HO) is a common complication following total hip replacement, affecting up to 45% of individuals. Fortunately severe disease affects less than 5% of patients but can result in severe restriction of movement and pain. HO also occurs in victims of blast injury, major trauma, and head injury, and is thus commonly seen in individuals involved in military conflict. We have recently conducted a genome wide scan for HO in 850 patients after hip replacement. Here we seek to replicate by Sequenom identified independent signals in an independent population of 500 individuals after hip replacement (approximately 50% with HO)","abstract":"Heterotopic ossification (HO) is a common complication following total hip replacement, affecting up to 45% of individuals. Fortunately severe disease affects less than 5% of patients but can result in severe restriction of movement and pain. HO also occurs in victims of blast injury, major trauma, and head injury, and is thus commonly seen in individuals involved in military conflict. We have recently conducted a genome wide scan for HO in 850 patients after hip replacement. Here we seek to replicate by Sequenom identified independent signals in an independent population of 500 individuals after hip replacement (approximately 50% with HO)","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004668","title":"Transcriptomic intra-tumor heterogeneity of colorectal cancer varies depending on tumor location within the colorectum","description":"Background; Intra-tumor heterogeneity (ITH) of colorectal cancer (CRC) complicates molecular tumor classification, such as transcriptional subtyping. Differences in cellular states, biopsy cell composition, and tumor microenvironment may all lead to ITH. Here we analyze ITH at the transcriptomic and proteomic levels to ascertain whether subtype discordance between multiregional biopsies reflects relevant biological ITH or lack of classifier robustness. Further, we study the impact of tumor location on ITH.MethodsMultiregional biopsies from stage II and III CRC tumors were analyzed by RNA sequencing (41 biopsies, 14 tumors) and multiplex immune protein analysis (89 biopsies, 29 tumors). CRC subtyping were performed using consensus molecular subtypes (CMS), CRC intrinsic subtypes (CRIS), and TUMOR types. ITH-scores and network maps were defined to determine the origin of heterogeneity. A validation cohort was used with one biopsy per tumor (162 tumors).ResultsOverall, inter-tumor transcriptional variation exceeded ITH, and subtyping calls were frequently concordant between multiregional biopsies. Still, some tumors had high ITH and were classified discordantly. Proximal tumors showed ITH related to differences in the microenvironment, while ITH within distal tumors were cancer-cell related. This subtype discordancy reflected actual molecular ITH within the tumors. The relevance of the subtypes was reflected at protein level where several inflammation markers were significantly increased in immune related transcriptional subtypes, which was verified in an independent cohort (Wilcoxon rank sum test; p&lt;0.05).ConclusionOur transcriptomic and proteomic analyses show that the tumor location along the colorectum influence the ITH of CRC, which again influence the concordance of subtyping.","abstract":"Background; Intra-tumor heterogeneity (ITH) of colorectal cancer (CRC) complicates molecular tumor classification, such as transcriptional subtyping. Differences in cellular states, biopsy cell composition, and tumor microenvironment may all lead to ITH. Here we analyze ITH at the transcriptomic and proteomic levels to ascertain whether subtype discordance between multiregional biopsies reflects relevant biological ITH or lack of classifier robustness. Further, we study the impact of tumor location on ITH.MethodsMultiregional biopsies from stage II and III CRC tumors were analyzed by RNA sequencing (41 biopsies, 14 tumors) and multiplex immune protein analysis (89 biopsies, 29 tumors). CRC subtyping were performed using consensus molecular subtypes (CMS), CRC intrinsic subtypes (CRIS), and TUMOR types. ITH-scores and network maps were defined to determine the origin of heterogeneity. A validation cohort was used with one biopsy per tumor (162 tumors).ResultsOverall, inter-tumor transcriptional variation exceeded ITH, and subtyping calls were frequently concordant between multiregional biopsies. Still, some tumors had high ITH and were classified discordantly. Proximal tumors showed ITH related to differences in the microenvironment, while ITH within distal tumors were cancer-cell related. This subtype discordancy reflected actual molecular ITH within the tumors. The relevance of the subtypes was reflected at protein level where several inflammation markers were significantly increased in immune related transcriptional subtypes, which was verified in an independent cohort (Wilcoxon rank sum test; p&lt;0.05).ConclusionOur transcriptomic and proteomic analyses show that the tumor location along the colorectum influence the ITH of CRC, which again influence the concordance of subtyping.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-15T12:53:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004669","title":"Exploration of coding and non-coding variants in cancer using GenomePaint.","description":"GenomePaint (https://proteinpaint.stjude.org/genomepaint) is a dynamic visualization platform for whole-genome, whole-exome, transcriptome, and epigenomic data, featuring a novel design that captures the inter-relatedness between DNA variations and RNA expression. Regulatory non-coding variants can be inspected and discovered along with coding variants, and their functional impact further explored by examining 3D genome and/or ChIP-seq data generated from cancer cell lines. Further, GenomePaint correlates mutation and expression patterns with patient outcomes, and can display external data such as adult cancer datasets and user-provided custom tracks. We used GenomePaint to analyze multi-omics data from 3,652 pediatric cancers representing 16 histotypes, and demonstrate the visualization features through examples, including two that led to new insights into oncogenic mechanisms in pediatric cancer. The first is the discovery of a new class of pathogenic recurrent variants that cause aberrant splicing, disrupting the RING domain of CREBBP, a driver gene frequently mutated in relapsed pediatric leukemia. The second is the cis-activation of the MYC oncogene in a subset of B-lineage acute lymphoblastic leukemia (B-ALL) via duplication of the NOTCH1-MYC enhancer (N-ME), previously discovered only in T-lineage ALL. The regulatory impact of N-ME enhancer amplification was initially confirmed by allelic imbalance in published gene expression and ChIP-seq data and verified by additional Capture-C and fluorescence in situ hybridization data generated by follow-up experiments. These examples demonstrate the power of GenomePaint in enabling not only data visualization but also integrative genomic analysis that can lead to novel biological insight for follow-up experimental validation.","abstract":"GenomePaint (https://proteinpaint.stjude.org/genomepaint) is a dynamic visualization platform for whole-genome, whole-exome, transcriptome, and epigenomic data, featuring a novel design that captures the inter-relatedness between DNA variations and RNA expression. Regulatory non-coding variants can be inspected and discovered along with coding variants, and their functional impact further explored by examining 3D genome and/or ChIP-seq data generated from cancer cell lines. Further, GenomePaint correlates mutation and expression patterns with patient outcomes, and can display external data such as adult cancer datasets and user-provided custom tracks. We used GenomePaint to analyze multi-omics data from 3,652 pediatric cancers representing 16 histotypes, and demonstrate the visualization features through examples, including two that led to new insights into oncogenic mechanisms in pediatric cancer. The first is the discovery of a new class of pathogenic recurrent variants that cause aberrant splicing, disrupting the RING domain of CREBBP, a driver gene frequently mutated in relapsed pediatric leukemia. The second is the cis-activation of the MYC oncogene in a subset of B-lineage acute lymphoblastic leukemia (B-ALL) via duplication of the NOTCH1-MYC enhancer (N-ME), previously discovered only in T-lineage ALL. The regulatory impact of N-ME enhancer amplification was initially confirmed by allelic imbalance in published gene expression and ChIP-seq data and verified by additional Capture-C and fluorescence in situ hybridization data generated by follow-up experiments. These examples demonstrate the power of GenomePaint in enabling not only data visualization but also integrative genomic analysis that can lead to novel biological insight for follow-up experimental validation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-15T18:09:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004670","title":"Copy number profiling of circulating cell-free DNA from high grade serous ovarian cancer patients","description":null,"abstract":"In order to find better markers of disease relapse and progression in high grade serous epithelial ovarian cancer (HGS-EOC) , we studied a cohort of 46 HGS-EOC patients with multiple plasma samples taken from diagnosis, throughout treatment and during follow up. \n\nWe used shallow whole genome sequeincing (sWGS) with depths ranging from 0.5X to 1X to characterize the tumor fraction present in the samples, the copy number instability (CNI), and we sought to investigate whether the use of tumor fraction and the analysis of recurrent copy number alteration events would be a good measurement of the patient status over time.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-17T10:19:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004671","title":"TCR β-chain repertoire characterization of regulatory and conventional T cells in breast tumors from breast cancer patients.","description":"Identification of tumor-specific effects on peripheral TCRβ repertoire formation in humans, investigation of the clonal origin of regulatory T cells in breast cancer patients and impact analysis of the tumor-specific conversion of conventional T cells into induced regulatory T cells on the peripheral Treg repertoire in humans.","abstract":"Identification of tumor-specific effects on peripheral TCRβ repertoire formation in humans, investigation of the clonal origin of regulatory T cells in breast cancer patients and impact analysis of the tumor-specific conversion of conventional T cells into induced regulatory T cells on the peripheral Treg repertoire in humans.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-17T10:38:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004672","title":"mutational landscape of normal human breast","description":"The accumulation of somatic mutations in the healthy breast throughout life and pregnancy is poorly understood. Here we describe whole genome sequencing analysis of epithelial and stromal compartments from the normal breast. We aimed to study how pregnancy and age affect both the mutational burden and the clonality of the healthy breast, and the subsequent implications on breast cancer risk.","abstract":"The accumulation of somatic mutations in the healthy breast throughout life and pregnancy is poorly understood. Here we describe whole genome sequencing analysis of epithelial and stromal compartments from the normal breast. We aimed to study how pregnancy and age affect both the mutational burden and the clonality of the healthy breast, and the subsequent implications on breast cancer risk.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-17T10:58:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004673","title":"Genomic profiling of patient-derived xenografts and organoids in prostate cancer","description":null,"abstract":"Therapy resistance and metastatic processes in prostate cancer remain undefined, due to lack of experimental models that mimic different disease stages. This project aims to profile the repertoire of somatic genetic alterations in novel PCa patient-derived xenograft and organoids models.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-17T11:45:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004674","title":"Foetal_phylogeny_8pcw___WGS_of_LCM_tissues","description":"This study relates to the overall project of constructing the phylogeny of foetal haematopoiesis. This is an additional project relating to pre-existing work in projects 2043, 2169, 2243 and 2244. This project is to perform WGS (to around 40X) of polyclonal LCM tissues from the 8pcw foetus that have previously undergone library prep and targeted sequencing only.  This work is to address reviewers comments for the publication of this work.","abstract":"This study relates to the overall project of constructing the phylogeny of foetal haematopoiesis. This is an additional project relating to pre-existing work in projects 2043, 2169, 2243 and 2244. This project is to perform WGS (to around 40X) of polyclonal LCM tissues from the 8pcw foetus that have previously undergone library prep and targeted sequencing only.  This work is to address reviewers comments for the publication of this work.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-17T13:51:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004675","title":"Transcriptomic profiling of patient-derived xenografts and organoids in prostate cancer","description":null,"abstract":"Therapy resistance and metastatic processes in prostate cancer remain undefined, due to lack of experimental models that mimic different disease stages. This project aims to perform transcriptomic profiling of novel PCa patient-derived xenograft and organoids models.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-18T19:09:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004676","title":"BLU-285 Biomarker Study","description":null,"abstract":"BLU-285 Biomarker Study","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004677","title":"Organoid_Derivation_Project___GRCh38___RNAseq","description":"Generation of normal and cancer organoids for sequencing as part of the WTSI-CRUK international collaboration with NCI (in HCMI) to generate the next generation of cancer cell lines.","abstract":"Generation of normal and cancer organoids for sequencing as part of the WTSI-CRUK international collaboration with NCI (in HCMI) to generate the next generation of cancer cell lines.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-18T22:22:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004678","title":"Recurrent SPECC1L-NTRK fusions in diverse paediatric cancers","description":null,"abstract":"The identification of rearrangements driving expression of Neurotrophic Receptor Tyrosine Kinase (NTRK) family kinases in tumours has become critically important due to the availability of effective, specific inhibitor drugs. Whole Genome Sequencing (WGS) combined with RNA Sequencing (RNAseq) can identify novel and recurrent expressed fusions. Here we describe three SPECC1L-NTRK fusions identified in two paediatric CNS cancers and an extracranial solid tumour using WGS and RNAseq. These fusions arose either through a simple balanced rearrangement, or in the context of a complex chromoplexy event. We cloned the SPECC1L-NTRK2 fusion directly from a patient sample and showed that enforced expression of this fusion is sufficient to promote cytokine-independent survival and proliferation. Cells transformed by SPECC1L-NTRK2 expression are sensitive to a TRK inhibitor drug. This is the first description that SPECC1L-NTRK fusions are recurrent in a range of paediatric cancers. Methods that can detect all NTRK fusions, such as WGS and RNAseq, offer the best chance of early identification and targeted treatment.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004679","title":"Recurrent SPECC1L-NTRK fusions in diverse paediatric cancers","description":null,"abstract":"The identification of rearrangements driving expression of Neurotrophic Receptor Tyrosine Kinase (NTRK) family kinases in tumours has become critically important due to the availability of effective, specific inhibitor drugs. Whole Genome Sequencing (WGS) combined with RNA Sequencing (RNAseq) can identify novel and recurrent expressed fusions. Here we describe three SPECC1L-NTRK fusions identified in two paediatric CNS cancers and an extracranial solid tumour using WGS and RNAseq. These fusions arose either through a simple balanced rearrangement, or in the context of a complex chromoplexy event. We cloned the SPECC1L-NTRK2 fusion directly from a patient sample and showed that enforced expression of this fusion is sufficient to promote cytokine-independent survival and proliferation. Cells transformed by SPECC1L-NTRK2 expression are sensitive to a TRK inhibitor drug. This is the first description that SPECC1L-NTRK fusions are recurrent in a range of paediatric cancers. Methods that can detect all NTRK fusions, such as WGS and RNAseq, offer the best chance of early identification and targeted treatment.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004680","title":"Multifocal ileal NETs study WES","description":null,"abstract":"Ileal neuroendocrine tumors (NETs) represent the most common neoplasm of the small intestine. Although up to 50% of patients with ileal NETs are diagnosed with multifocal disease, the mechanisms by which multifocal ileal NETs arise are not yet understood. In this study, we analyzed genome-wide sequencing data to examine patterns of copy number variation in 40 synchronous primary ileal NETs derived from three patients. Chromosome (chr) 18 loss of heterozygosity (LOH) was the most frequent copy number alteration identified; however, not all primary tumors from the same patient had evidence of this LOH. Our data revealed three distinct patterns of chr18 allelic loss, indicating that primary tumors from the same patient can present different LOH patterns including retention of either parental allele. In conclusion, our results are consistent with the model that multifocal ileal NETs originate independently. In addition, they suggest that there is no specific germline allele on chr18 that is the target of somatic LOH.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-21T02:05:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004681","title":"Multifocal ileal NETs study WGS HFF7VCCXY","description":null,"abstract":"Ileal neuroendocrine tumors (NETs) represent the most common neoplasm of the small intestine. Although up to 50% of patients with ileal NETs are diagnosed with multifocal disease, the mechanisms by which multifocal ileal NETs arise are not yet understood. In this study, we analyzed genome-wide sequencing data to examine patterns of copy number variation in 40 synchronous primary ileal NETs derived from three patients. Chromosome (chr) 18 loss of heterozygosity (LOH) was the most frequent copy number alteration identified; however, not all primary tumors from the same patient had evidence of this LOH. Our data revealed three distinct patterns of chr18 allelic loss, indicating that primary tumors from the same patient can present different LOH patterns including retention of either parental allele. In conclusion, our results are consistent with the model that multifocal ileal NETs originate independently. In addition, they suggest that there is no specific germline allele on chr18 that is the target of somatic LOH.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-21T03:32:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004682","title":"International consensus definition of DNA methylation subgroups in juvenile myelomonocytic leukemia","description":"Known clinical and genetic markers have limitations in predicting disease course and outcome in juvenile myelomonocytic leukemia (JMML). DNA methylation (DNAme) patterns in JMML have correlated with outcome across multiple studies, suggesting it as a biomarker to improve patient stratification. However, standardized approaches to classify JMML based on DNAme patterns are lacking. We therefore sought to define an international consensus for DNAme subgroups in JMML and develop classification methods for clinical implementation.","abstract":"Known clinical and genetic markers have limitations in predicting disease course and outcome in juvenile myelomonocytic leukemia (JMML). DNA methylation (DNAme) patterns in JMML have correlated with outcome across multiple studies, suggesting it as a biomarker to improve patient stratification. However, standardized approaches to classify JMML based on DNAme patterns are lacking. We therefore sought to define an international consensus for DNAme subgroups in JMML and develop classification methods for clinical implementation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-21T08:05:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004683","title":"Molecular analysis of FIT interval colorectal cancers","description":"To optimize a fecal immunochemical test-based screening program, the rate of missed colorectal cancers (CRCs), so-called FIT-interval CRCs, should be minimized. A specific molecular make-up of those CRCs could be an explanation for those interval CRCs. Knowledge of the molecular make-up of these missed lesions could facilitate more accurate detection of all precursor lesions. In this study we aimed to compare the molecular make-up of FIT-interval CRCs and screen-detected CRCs (SD-CRCs).","abstract":"To optimize a fecal immunochemical test-based screening program, the rate of missed colorectal cancers (CRCs), so-called FIT-interval CRCs, should be minimized. A specific molecular make-up of those CRCs could be an explanation for those interval CRCs. Knowledge of the molecular make-up of these missed lesions could facilitate more accurate detection of all precursor lesions. In this study we aimed to compare the molecular make-up of FIT-interval CRCs and screen-detected CRCs (SD-CRCs).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-21T08:17:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004684","title":"Allele-specific expression of GATA2 due to epigenetic dysregulation in double mutated CEBPA AML","description":"Transcriptional deregulation is a central event in the development of acute myeloid leukemia (AML). To identify potential disturbances in gene regulation, we conducted an unbiased screen of allele-specific expression (ASE) in 209 AML cases. The gene encoding GATA binding protein 2 (GATA2) displayed ASE more often than any other myeloid or cancer-related gene. GATA2 ASE was strongly associated with CEBPA double mutations (CEBPA DM), with 95% of cases presenting GATA2 ASE. In CEBPA DM AML with GATA2 mutations, the mutated allele was preferentially expressed. We found that GATA2 ASE is a somatic event lost in complete remission, supporting the notion that it plays a role in CEBPA DM AML. Acquisition of GATA2 ASE involved silencing of one allele via promoter methylation, compensated by overactivation of the other allele, thereby preserving expression levels. Notably, promoter methylation was also lost in remission together with GATA2 ASE. In summary, we propose that GATA2 ASE is acquired by epigenetic mechanisms and is a prerequisite for the development of AML with CEBPA DM. This finding constitutes a novel example of an epigenetic hit cooperating with a genetic hit in the pathogenesis of AML.","abstract":"Transcriptional deregulation is a central event in the development of acute myeloid leukemia (AML). To identify potential disturbances in gene regulation, we conducted an unbiased screen of allele-specific expression (ASE) in 209 AML cases. The gene encoding GATA binding protein 2 (GATA2) displayed ASE more often than any other myeloid or cancer-related gene. GATA2 ASE was strongly associated with CEBPA double mutations (CEBPA DM), with 95% of cases presenting GATA2 ASE. In CEBPA DM AML with GATA2 mutations, the mutated allele was preferentially expressed. We found that GATA2 ASE is a somatic event lost in complete remission, supporting the notion that it plays a role in CEBPA DM AML. Acquisition of GATA2 ASE involved silencing of one allele via promoter methylation, compensated by overactivation of the other allele, thereby preserving expression levels. Notably, promoter methylation was also lost in remission together with GATA2 ASE. In summary, we propose that GATA2 ASE is acquired by epigenetic mechanisms and is a prerequisite for the development of AML with CEBPA DM. This finding constitutes a novel example of an epigenetic hit cooperating with a genetic hit in the pathogenesis of AML.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-21T14:15:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004685","title":"Low-C of human cord-blood derived LT-HSC and ST-HSC","description":null,"abstract":"Low-C was performed upon human cord-blood long-term hematopoietic stem cells (LT-HSC) and short-term hematopoietic stem cells (ST-HSC). This was used to demonstrate that chromatin conformation changes associated with LT-HSC activation are enriched in ST-HSC.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004686","title":"Molecular analysis of post-colonoscopy CRC (PCCRC)","description":"Background: Post-colonoscopy colorectal cancers (PCCRCs, i.e. CRC diagnosed after a colonoscopy that excluded cancer) pose a challenge in clinical practice. In a retrospective cohort study, we compared clinical and molecular features of PCCRCs and prevalent CRCs.\nMethods: PCCRCs were defined according to the WEO classification, as cancers occurring within 10 years after a complete index colonoscopy, which excluded CRC. Whole genome chromosomal copy number changes and mutation status of genes commonly affected in CRC (APC, KRAS, BRAF, FBXW7, PIK3CA, NRAS, SMAD4 and TP53) were examined by low-coverage WGS and targeted sequencing, respectively. MSI and CIMP status were also determined.\nResults: In total, 122 PCCRCs and 98 prevalent CRCs were examined. PCCRCs are more often located proximally in the colon (p&lt;0.001), non-polypoid appearing (p=0.004), early stage (p=0.009), and poorly differentiated (p=0.006) compared to prevalent CRCs. PCCRCs contain less frequently 18q deletions (p&lt;0.001) than prevalent CRCs. MSI (p=0.029) and CIMP (p=0.014) are more frequently observed in PCCRCs.\nConclusion: Although no PCCRC specific pathway could be defined, PCCRCs’ molecular features are more associated with MSI and hypermethylation pathways than canonical CIN pathway. The clinical and molecular features observed in PCCRCs support the hypothesis that sessile serrated lesions and non-polypoid CRNs are contributors to the development of these cancers.\"","abstract":"Background: Post-colonoscopy colorectal cancers (PCCRCs, i.e. CRC diagnosed after a colonoscopy that excluded cancer) pose a challenge in clinical practice. In a retrospective cohort study, we compared clinical and molecular features of PCCRCs and prevalent CRCs.\nMethods: PCCRCs were defined according to the WEO classification, as cancers occurring within 10 years after a complete index colonoscopy, which excluded CRC. Whole genome chromosomal copy number changes and mutation status of genes commonly affected in CRC (APC, KRAS, BRAF, FBXW7, PIK3CA, NRAS, SMAD4 and TP53) were examined by low-coverage WGS and targeted sequencing, respectively. MSI and CIMP status were also determined.\nResults: In total, 122 PCCRCs and 98 prevalent CRCs were examined. PCCRCs are more often located proximally in the colon (p&lt;0.001), non-polypoid appearing (p=0.004), early stage (p=0.009), and poorly differentiated (p=0.006) compared to prevalent CRCs. PCCRCs contain less frequently 18q deletions (p&lt;0.001) than prevalent CRCs. MSI (p=0.029) and CIMP (p=0.014) are more frequently observed in PCCRCs.\nConclusion: Although no PCCRC specific pathway could be defined, PCCRCs’ molecular features are more associated with MSI and hypermethylation pathways than canonical CIN pathway. The clinical and molecular features observed in PCCRCs support the hypothesis that sessile serrated lesions and non-polypoid CRNs are contributors to the development of these cancers.\"","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-22T09:04:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004687","title":"Molecular pathways in post-colonoscopy versus prevalent colorectal cancers: results from a population-based cohort study","description":null,"abstract":"160 post-colonoscopy CRC samples (post-colonoscopy CRCs, or post-colonoscopy interval cancers) have been sequenced with low coverage whole genome sequencing to determine copy number aberrations.\n70 interval colorectal cancer samples, 90 sporadic colorectal cancer samples","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004688","title":"test","description":null,"abstract":"test","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004689","title":"COVID-19 Postmortem Lung snRNA-seq","description":"A deeper understanding of the pathological mechanisms of SARS-CoV-2 infection is required to combat COVID-19. Through this dataset, we analyze postmortem lung cells from patients that are infected/uninfected with SARS-CoV-2 with snRNA-seq.","abstract":"A deeper understanding of the pathological mechanisms of SARS-CoV-2 infection is required to combat COVID-19. Through this dataset, we analyze postmortem lung cells from patients that are infected/uninfected with SARS-CoV-2 with snRNA-seq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-22T17:04:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004690","title":"Hi-C of the OCIAML-2 Cell line","description":null,"abstract":"2.5M OCI-AML2 cells per replicate according to previously reported protocol (Rao et al. 2014) with DPNII as a restriction enzyme. Libraries  were sequenced using the NextSeq (Illumina) to generate paired-end 150-bp reads. Reads from 6 separate Hi-C replicates, were pooled together.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004691","title":"Whole-exome sequencing of acute megakaryoblastic leukemias in Down syndrome","description":null,"abstract":"We performed WES of additional 39 DS-AMKL samples using remission samples as controls. The mean number of non-silent somatic mutations was 6.7 (range: 1-17). Significantly higher (&gt;1) dN/dS ratio was observed in 20 genes , including 6 novel driver genes in DS-AMKL.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004692","title":"PCR-free shallow whole genome sequencing for chromosomal copy number detection from plasma of cancer patients is an efficient alternative to the conventional PCR-based approach","description":"Somatic copy number alterations (SCNAs) can be detected in tumor cell-free DNA (cfDNA) by shallow whole genome sequencing (sWGS). Polymerase chain reaction (PCR) is typically included in library preparations, but a PCR-free method could be an effective alternative for research and diagnostics. Peripheral blood samples (n=22) were collected in EDTA-containing tubes from non-small cell lung cancer patients (n=10) and healthy donors (n=12). PCR and PCR-free library preparations underwent sWGS and the following metrics were compared: mapping quality, proportion of duplicate reads, genome coverage, sequencing read length and copy number profiles. The PCR-free method was further evaluated on archived plasma samples (n=33) of varying pre-analytical quality collected in EDTA or lithium heparin tubes. Archived samples were from acute myeloid leukaemia (n=15) and B-cell lymphoma (n=18) patients. The percentage of unique reads was significantly higher for the 22 samples analysed by PCR-free (95.7%) compared to PCR (84%). PCR-free libraries from 33 archived samples produced data of a comparable quality, with 95.4% unique reads. All other evaluated  metrics were highly comparable for PCR and PCR-free library preparations. We conclude that SCNA detection can be performed by PCR-free sWGS on cfDNA from cancer patients and is feasible for diagnostic and archival plasma collected in EDTA- or lithium heparin-containing tubes. Our results pave the way for an automated cfDNA workflow for cancer plasma samples.","abstract":"Somatic copy number alterations (SCNAs) can be detected in tumor cell-free DNA (cfDNA) by shallow whole genome sequencing (sWGS). Polymerase chain reaction (PCR) is typically included in library preparations, but a PCR-free method could be an effective alternative for research and diagnostics. Peripheral blood samples (n=22) were collected in EDTA-containing tubes from non-small cell lung cancer patients (n=10) and healthy donors (n=12). PCR and PCR-free library preparations underwent sWGS and the following metrics were compared: mapping quality, proportion of duplicate reads, genome coverage, sequencing read length and copy number profiles. The PCR-free method was further evaluated on archived plasma samples (n=33) of varying pre-analytical quality collected in EDTA or lithium heparin tubes. Archived samples were from acute myeloid leukaemia (n=15) and B-cell lymphoma (n=18) patients. The percentage of unique reads was significantly higher for the 22 samples analysed by PCR-free (95.7%) compared to PCR (84%). PCR-free libraries from 33 archived samples produced data of a comparable quality, with 95.4% unique reads. All other evaluated  metrics were highly comparable for PCR and PCR-free library preparations. We conclude that SCNA detection can be performed by PCR-free sWGS on cfDNA from cancer patients and is feasible for diagnostic and archival plasma collected in EDTA- or lithium heparin-containing tubes. Our results pave the way for an automated cfDNA workflow for cancer plasma samples.","study_type":"Cancer Genomics","pubmed_ids":[34454114],"external_links":null,"is_released":true,"released_date":"2025-06-17T15:21:58.647617+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004693","title":"UROMOL 2020 - RNA-seq data","description":"The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we performed a large integrative multi-omics analysis of patients diagnosed with NMIBC (n=834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters.","abstract":"The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we performed a large integrative multi-omics analysis of patients diagnosed with NMIBC (n=834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-24T10:08:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004694","title":"Regulatory T cell transcriptomic reprogramming characterizes adverse events by checkpoint inhibitors in solid tumors","description":"Immune checkpoint inhibitors (ICI), which target immune regulatory pathways to unleash antitumor responses, have revolutionized cancer immunotherapy. Despite the remarkable success of ICI immunotherapy, a significant proportion of patients whose tumors respond to these treatments develop immune-related adverse events (irAEs) resembling autoimmune diseases. Although the clinical spectrum of irAEs is well characterized, their successful management remains empiric. This is in part because the pathogenic mechanisms involved in the break-down of peripheral tolerance and induction of irAEs remain elusive. Herein, we focused on regulatory T cells (Tregs) in individuals with irAEs because these cells are vital for maintenance of peripheral tolerance, appear expanded in the peripheral blood of individuals with cancer and abundantly express checkpoint molecules, hence representing direct targets of ICI immunotherapy. Our data demonstrate an intense transcriptomic reprogramming of CD4+CD25+CD127– Tregs in the blood of individuals with advanced metastatic melanoma who develop irAEs following ICI immunotherapy, with a characteristic inflammatory, apoptotic and metabolic signature. This inflammatory signature was shared by Tregs from individuals with different types of cancer developing irAEs and individuals with autoimmune diseases. Our findings propose an inflammatory Treg reprogramming as a feature of immunotherapy-induced irAEs, that may facilitate translational approaches aiming to induce robust antitumor immunity without disturbing peripheral tolerance.","abstract":"Immune checkpoint inhibitors (ICI), which target immune regulatory pathways to unleash antitumor responses, have revolutionized cancer immunotherapy. Despite the remarkable success of ICI immunotherapy, a significant proportion of patients whose tumors respond to these treatments develop immune-related adverse events (irAEs) resembling autoimmune diseases. Although the clinical spectrum of irAEs is well characterized, their successful management remains empiric. This is in part because the pathogenic mechanisms involved in the break-down of peripheral tolerance and induction of irAEs remain elusive. Herein, we focused on regulatory T cells (Tregs) in individuals with irAEs because these cells are vital for maintenance of peripheral tolerance, appear expanded in the peripheral blood of individuals with cancer and abundantly express checkpoint molecules, hence representing direct targets of ICI immunotherapy. Our data demonstrate an intense transcriptomic reprogramming of CD4+CD25+CD127– Tregs in the blood of individuals with advanced metastatic melanoma who develop irAEs following ICI immunotherapy, with a characteristic inflammatory, apoptotic and metabolic signature. This inflammatory signature was shared by Tregs from individuals with different types of cancer developing irAEs and individuals with autoimmune diseases. Our findings propose an inflammatory Treg reprogramming as a feature of immunotherapy-induced irAEs, that may facilitate translational approaches aiming to induce robust antitumor immunity without disturbing peripheral tolerance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-24T11:03:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004695","title":"Human gastrointestinal epithelia of the esophagus, stomach and duodenum resolved at single-cell resolution","description":null,"abstract":"The upper gastrointestinal tract consisting of the esophagus, stomach and duodenum controls food transport, digestion, nutrient uptake and hormone production. By single-cell analysis of healthy epithelia of these human organs, we molecularly defined their distinct cell types. We identified a quiescent COL17A1high stem/progenitor cell population within the most basal cell layer of the esophagus and detected substantial gene expression differences between identical cell types of the human and mouse stomach. Selective and high expression of BEST4, CFTR, guanylin and uroguanylin identified a new rare cell type in the duodenum, referred to as BCHE cells, which likely mediate high-volume fluid secretion due to continual activation of the CFTR channel by guanylin/uroguanylin-mediated autocrine signaling. Previously uncharacterized serotonin-producing enterochromaffin cells in the antral stomach are shown to significantly differ in gene expression from the duodenal enterochromaffin cells. We furthermore discovered that the histamine-producing enterochromaffin-like cells in the oxyntic stomach express the luteinizing hormone, which was not previously seen in enteroendocrine cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-25T11:58:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004696","title":"Nuclease deficiencies alter plasma cell-free DNA methylationprofiles (mouse)","description":"The effects of DNASE1L3 or DNASE1 deficiency on cfDNA methylation was explored in plasma of mice deficient in these nucleases and in DNASE1L3-deficient humans. Compared to wildtype cfDNA, cfDNA in Dnase1l3-deficient mice was significantly hypomethylated, while cfDNA in Dnase1-deficient mice was hypermethylated. The cfDNA hypomethylation in Dnase1l3-deficient mice was due to increased fragmentation and representation from open chromatin regions (OCRs) and CpG islands (CGIs). These findings were absent in Dnase1-deficient mice.","abstract":"The effects of DNASE1L3 or DNASE1 deficiency on cfDNA methylation was explored in plasma of mice deficient in these nucleases and in DNASE1L3-deficient humans. Compared to wildtype cfDNA, cfDNA in Dnase1l3-deficient mice was significantly hypomethylated, while cfDNA in Dnase1-deficient mice was hypermethylated. The cfDNA hypomethylation in Dnase1l3-deficient mice was due to increased fragmentation and representation from open chromatin regions (OCRs) and CpG islands (CGIs). These findings were absent in Dnase1-deficient mice.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-27T03:35:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004697","title":"Ultraviolet radiation drives mutations in a subset of mucosal melanomas","description":"Although identified as the key environmental driver of common cutaneous melanoma, the role of ultraviolet radiation (UVR)-induced DNA damage in mucosal melanoma is poorly defined. We present the largest cohort of mucosal melanomas of conjunctival origin to be analyzed by whole genome sequencing and show a predominance of UVR-associated single base substitution signature 7 (SBS7) in the majority of the samples. Our data shows mucosal melanomas with SBS7 dominance have similar genomic patterns to cutaneous melanomas and therefore this subset could benefit from treatments currently used for common cutaneous melanoma.","abstract":"Although identified as the key environmental driver of common cutaneous melanoma, the role of ultraviolet radiation (UVR)-induced DNA damage in mucosal melanoma is poorly defined. We present the largest cohort of mucosal melanomas of conjunctival origin to be analyzed by whole genome sequencing and show a predominance of UVR-associated single base substitution signature 7 (SBS7) in the majority of the samples. Our data shows mucosal melanomas with SBS7 dominance have similar genomic patterns to cutaneous melanomas and therefore this subset could benefit from treatments currently used for common cutaneous melanoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-09-29T12:45:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004698","title":"Molecular characterization of medulloblastoma PDX models","description":"Medulloblastoma (MB) is among the most common malignant brain tumors in children. Recent studies have identified at least four subgroups of the disease that differ in terms of molecular characteristics and patient outcomes. Despite this heterogeneity, most MB patients receive similar therapies, including surgery, radiation and intensive chemotherapy. Although these treatments prolong survival, many patients still die from the disease, and survivors suffer severe long-term side effects from therapy. We hypothesize that each MB patient is sensitive to different therapies, and that tailoring therapy based on the molecular and cellular characteristics of patients’ tumors will improve outcomes. To test this, we have assembled a panel of orthotopic patient-derived xenografts (PDXs) and subjected them to DNA sequencing, gene expression profiling and high-throughput drug screening. Analysis of DNA sequencing suggests that most MBs do not have actionable mutations that point to effective therapies. In contrast, gene expression and drug response data provide valuable information about potential therapies for every tumor. For example, drug screening demonstrates that actinomycin D – which is used for treatment of sarcoma but rarely for MB – is active against PDXs representing Group 3 MB, the most aggressive form of the disease. Finally, we show that expression analysis and drug screening can be used in a clinical setting to identify more treatment options than mutational analysis alone. These studies suggest that it should be possible to move away from a one-size-fits-all approach and begin to treat each patient with therapies that are effective against their tumor.","abstract":"Medulloblastoma (MB) is among the most common malignant brain tumors in children. Recent studies have identified at least four subgroups of the disease that differ in terms of molecular characteristics and patient outcomes. Despite this heterogeneity, most MB patients receive similar therapies, including surgery, radiation and intensive chemotherapy. Although these treatments prolong survival, many patients still die from the disease, and survivors suffer severe long-term side effects from therapy. We hypothesize that each MB patient is sensitive to different therapies, and that tailoring therapy based on the molecular and cellular characteristics of patients’ tumors will improve outcomes. To test this, we have assembled a panel of orthotopic patient-derived xenografts (PDXs) and subjected them to DNA sequencing, gene expression profiling and high-throughput drug screening. Analysis of DNA sequencing suggests that most MBs do not have actionable mutations that point to effective therapies. In contrast, gene expression and drug response data provide valuable information about potential therapies for every tumor. For example, drug screening demonstrates that actinomycin D – which is used for treatment of sarcoma but rarely for MB – is active against PDXs representing Group 3 MB, the most aggressive form of the disease. Finally, we show that expression analysis and drug screening can be used in a clinical setting to identify more treatment options than mutational analysis alone. These studies suggest that it should be possible to move away from a one-size-fits-all approach and begin to treat each patient with therapies that are effective against their tumor.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004699","title":"HG_UKBB_scRNA_Pilot_I_II","description":"This is a 2 phase pilot , to optimise cell count, sequence depth and the size of jointly analysed pools of individuals to advance technologies to enable higher multiplexing , thus enabling a larger study to be designed in a cost effective scale","abstract":"This is a 2 phase pilot , to optimise cell count, sequence depth and the size of jointly analysed pools of individuals to advance technologies to enable higher multiplexing , thus enabling a larger study to be designed in a cost effective scale","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004700","title":"Network-based systems pharmacology identifies heterogeneity in LCK and BCL2 signaling and differential vulnerability of T-cell acute lymphoblastic leukemia to targeted therapy","description":"T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy, and novel therapeutics are much needed. Profiling patient leukemia’ drug sensitivities ex vivo, we discovered striking inter-patient variability in T-ALL response to a panel of targeted agents. Applying network-based systems pharmacology analyses, by integrating ex vivo pharmacotyping, bulk and single-cell RNA-seq, genomics, phospho-proteomics, and genome-wide CRISPR screening data, to examine signal circuitry, we identified the pharmacogenomic basis of T-ALL drug response and revealed a therapeutic vulnerability that is directly related to the developmental stage of leukemia cells. In conclusion, our results indicate that heterogeneity in the differentiation of T-ALL drives activation of key signaling pathways in this leukemia, providing unique opportunities for targeted therapy.","abstract":"T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy, and novel therapeutics are much needed. Profiling patient leukemia’ drug sensitivities ex vivo, we discovered striking inter-patient variability in T-ALL response to a panel of targeted agents. Applying network-based systems pharmacology analyses, by integrating ex vivo pharmacotyping, bulk and single-cell RNA-seq, genomics, phospho-proteomics, and genome-wide CRISPR screening data, to examine signal circuitry, we identified the pharmacogenomic basis of T-ALL drug response and revealed a therapeutic vulnerability that is directly related to the developmental stage of leukemia cells. In conclusion, our results indicate that heterogeneity in the differentiation of T-ALL drives activation of key signaling pathways in this leukemia, providing unique opportunities for targeted therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-02T16:09:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004701","title":"Integrative Analysis of Pediatric Acute Leukemia Identifies Acute Myeloid/T-Lymphoblastic Leukemia Subtype that Spans a T Lineage and Myeloid Continuum with Distinct Prognoses","description":"Genomic characterization of pediatric patients with acute myeloid leukemia (AML) has revealed age specific mutational spectrums, distinguishing it biologically from adult patients. While gene expression profiling signatures can differentiate subsets of pediatric AML, its clinical utility in risk stratification has remained limited.","abstract":"Genomic characterization of pediatric patients with acute myeloid leukemia (AML) has revealed age specific mutational spectrums, distinguishing it biologically from adult patients. While gene expression profiling signatures can differentiate subsets of pediatric AML, its clinical utility in risk stratification has remained limited.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-02T20:01:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004702","title":"Chromosomal copy number heterogeneity predicts survival rates across cancers","description":"Survival rates of cancer patients vary widely within and between malignancies. While genetic aberrations are at the root of all cancers, individual genomic features cannot explain these distinct disease outcomes. In contrast, intra-tumour heterogeneity (ITH) has the potential to elucidate pan-cancer survival rates and the biology that drives cancer prognosis1,2. Unfortunately, a comprehensive and effective framework to measure ITH across cancers is missing3. Here, we introduce a scalable measure of chromosomal copy number heterogeneity that predicts patient survival across cancers. We show that the level of ITH can be derived from a single-sample copy number profile. Using gene-expression data we demonstrate that ongoing chromosomal instability underlies the observed heterogeneity. Analysing 11,534 primary cancer samples from 35 different malignancies, we find that copy number heterogeneity can be accurately deduced and predicts cancer survival across tissues of origin and stages of disease. Our results provide a unifying molecular explanation for the different survival rates observed between cancer types.","abstract":"Survival rates of cancer patients vary widely within and between malignancies. While genetic aberrations are at the root of all cancers, individual genomic features cannot explain these distinct disease outcomes. In contrast, intra-tumour heterogeneity (ITH) has the potential to elucidate pan-cancer survival rates and the biology that drives cancer prognosis1,2. Unfortunately, a comprehensive and effective framework to measure ITH across cancers is missing3. Here, we introduce a scalable measure of chromosomal copy number heterogeneity that predicts patient survival across cancers. We show that the level of ITH can be derived from a single-sample copy number profile. Using gene-expression data we demonstrate that ongoing chromosomal instability underlies the observed heterogeneity. Analysing 11,534 primary cancer samples from 35 different malignancies, we find that copy number heterogeneity can be accurately deduced and predicts cancer survival across tissues of origin and stages of disease. Our results provide a unifying molecular explanation for the different survival rates observed between cancer types.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-05T15:03:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004703","title":"PRIM1 Deficiency Causes a Distinctive Primordial Dwarfism Syndrome","description":"DNA replication is fundamental for cell proliferation in all organisms. Nonetheless,components of the replisome have been implicated in human disease and here we report PRIM1, encoding the catalytic subunit of DNA primase, as a novel disease gene. Using a variant-classification agnostic approach, biallelic mutations in PRIM1 were identified in five individuals. PRIM1 protein levels were markedly reduced in patient cells, accompanied by replication fork asymmetry, increased inter-origin distances, replication stress and prolonged S-phase duration. Consequently, cell proliferation was markedly impaired, explaining the patients’ extreme growth failure. Notably, phenotypic features distinct from those previously reported with DNA polymerase genes were evident, highlighting differing developmental requirements for this core replisome component that warrant future investigation.","abstract":"DNA replication is fundamental for cell proliferation in all organisms. Nonetheless,components of the replisome have been implicated in human disease and here we report PRIM1, encoding the catalytic subunit of DNA primase, as a novel disease gene. Using a variant-classification agnostic approach, biallelic mutations in PRIM1 were identified in five individuals. PRIM1 protein levels were markedly reduced in patient cells, accompanied by replication fork asymmetry, increased inter-origin distances, replication stress and prolonged S-phase duration. Consequently, cell proliferation was markedly impaired, explaining the patients’ extreme growth failure. Notably, phenotypic features distinct from those previously reported with DNA polymerase genes were evident, highlighting differing developmental requirements for this core replisome component that warrant future investigation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004704","title":"A comprehensive characterization of the cell-free transcriptome reveals tissue- and subtype-specific biomarkers for cancer detection","description":"Cell-free RNA (cfRNA) is a promising analyte for cancer detection. However, a comprehensive assessment of cfRNA in individuals with and without cancer has not been conducted. We performed the first transcriptome-wide characterization of cfRNA in cancer (stage III breast [n=46], lung [n=30]) and non-cancer (n=89) participants from the Circulating Cell-free Genome Atlas (NCT02889978). Of 57,820 annotated genes, 39,564 (68%) were not detected in cfRNA from non-cancer individuals. Within these low-noise regions, we identified tissue- and cancer-specific genes, defined as \"dark channel biomarker\" (DCB) genes, that were recurrently detected in individuals with cancer. DCB levels in plasma were correlated with tumor shedding rate and RNA expression in matched tissue, suggesting that DCBs with high expression in tumor tissue could enhance cancer detection in patients with low levels of circulating tumor DNA. Overall, cfRNA provides a unique opportunity to detect cancer, predict the tumor tissue of origin, and determine the cancer subtype.","abstract":"Cell-free RNA (cfRNA) is a promising analyte for cancer detection. However, a comprehensive assessment of cfRNA in individuals with and without cancer has not been conducted. We performed the first transcriptome-wide characterization of cfRNA in cancer (stage III breast [n=46], lung [n=30]) and non-cancer (n=89) participants from the Circulating Cell-free Genome Atlas (NCT02889978). Of 57,820 annotated genes, 39,564 (68%) were not detected in cfRNA from non-cancer individuals. Within these low-noise regions, we identified tissue- and cancer-specific genes, defined as \"dark channel biomarker\" (DCB) genes, that were recurrently detected in individuals with cancer. DCB levels in plasma were correlated with tumor shedding rate and RNA expression in matched tissue, suggesting that DCBs with high expression in tumor tissue could enhance cancer detection in patients with low levels of circulating tumor DNA. Overall, cfRNA provides a unique opportunity to detect cancer, predict the tumor tissue of origin, and determine the cancer subtype.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-06T11:39:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004705","title":"Whole genome sequencing of EBV Associated Nasopharyngeal Carcinoma","description":"Interplay between EBV infection and acquired genetic alterations during nasopharyngeal carcinoma (NPC) development remains vague. Here we report a comprehensive genomic analysis of 70 NPCs, combining whole-genome sequencing (WGS) of microdissected tumor cells with EBV oncogene expression to reveal multiple aspects of cellular-viral co-operation in tumorigenesis. Genomic aberrations along with EBV-encoded LMP1 expression underpin constitutive NF-κB activation in 90% of NPCs. A similar spectrum of somatic aberrations and viral gene expression undermine innate immunity in 79% of cases and adaptive immunity in 47% of cases; mechanisms by which NPC may evade immune surveillance despite its pro inflammatory phenotype. Additionally, genomic changes impairing TGFBR2 promote oncogenesis and stabilize EBV infection in tumor cells. Fine-mapping of CDKN2A/CDKN2B deletion breakpoints reveals homozygous MTAP deletions in 32-34% of NPCs that confer marked sensitivity to MAT2A inhibition. Our work concludes that NPC is a homogeneously NF-κB-driven and immune-protected, yet potentially druggable, cancer.","abstract":"Interplay between EBV infection and acquired genetic alterations during nasopharyngeal carcinoma (NPC) development remains vague. Here we report a comprehensive genomic analysis of 70 NPCs, combining whole-genome sequencing (WGS) of microdissected tumor cells with EBV oncogene expression to reveal multiple aspects of cellular-viral co-operation in tumorigenesis. Genomic aberrations along with EBV-encoded LMP1 expression underpin constitutive NF-κB activation in 90% of NPCs. A similar spectrum of somatic aberrations and viral gene expression undermine innate immunity in 79% of cases and adaptive immunity in 47% of cases; mechanisms by which NPC may evade immune surveillance despite its pro inflammatory phenotype. Additionally, genomic changes impairing TGFBR2 promote oncogenesis and stabilize EBV infection in tumor cells. Fine-mapping of CDKN2A/CDKN2B deletion breakpoints reveals homozygous MTAP deletions in 32-34% of NPCs that confer marked sensitivity to MAT2A inhibition. Our work concludes that NPC is a homogeneously NF-κB-driven and immune-protected, yet potentially druggable, cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-07T11:49:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004706","title":"Pancreatic cancer RNA sequencing","description":null,"abstract":"For optimal pancreatic cancer treatment, early and accurate diagnosis is vital. Blood-derived biomarkers and genetic predispositions can contribute to early diagnosis, but they often have limited accuracy or applicability. Here, we seek to exploit the synergy between them by combining the biomarker CA19-9 with RNA-based variants. We use deep sequencing and deep learning to improve differentiating pancreatic cancer and chronic pancreatitis. We obtained samples of nucleated cells found in peripheral blood from 268 patients suffering from resectable, non-resectable pancreatic cancer, and chronic pancreatitis. We sequenced RNA with high coverage and obtained millions of variants. The high-quality variants served as input together with CA19-9 values to deep learning models. Our model achieved an area under the curve (AUC) of 96% in differentiating resectable cancer from pancreatitis using a test cohort. Moreover, we identified variants to estimate survival in resectable cancer. We show that the blood transcriptome harbours variants, which can substantially improve noninvasive clinical diagnosis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-07T13:15:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004707","title":"Resident memory CD8 T cell in human lung cancer","description":null,"abstract":"We use RNAseq to investigate the transcriptome of resident memory CD8 T cells (TRM) infiltrating human lung cancer. CD103+CD8+ T cells and KLRG1+CD8+ T cells (population paired) were sorted by flow cytometry from 7 primary non-small cell lung cancers to elucidate the genetic programs that underlie their immune functions. We compared the RNA expression profile of these two CD8 T cell populations to better describe CD103+CD8+ T cells, which correspond to TRM, and study their role in antitumor immunity.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-07T15:35:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004708","title":"RNA-Seq on human cord-blood derived LT-HSC transduced with shCTCF or  LacZ Control","description":null,"abstract":"RNA-Seq on human cord-blood derived LT-HSC transduced with shCTCF  or LacZ Control 3 days post transduction","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004709","title":"A novel orthotopic patient-derived xenograft model of radiation-induced glioma following medulloblastoma","description":"Radiation-induced glioma (RIG) is a highly aggressive brain cancer arising as a consequence of radiation therapy. We report a case of RIG that arose in the brain stem following treatment for paediatric medulloblastoma, and the development and characterisation of a matched orthotopic patient-derived xenograft (PDX) model (TK-RIG915). Patient and PDX tumours were analysed using DNA methylation profiling, whole genome sequencing (WGS) and RNA sequencing. While initially thought to be a diffuse intrinsic pontine glioma (DIPG) based on disease location, results from methylation profiling and WGS were not consistent with this diagnosis. Furthermore, clustering analyses based on RNA expression suggested the tumours were distinct from primary DIPG. Additional gene expression analysis demonstrated concordance with a published RIG expression profile. Multiple genetic alterations that enhance PI3K/AKT and Ras/Raf/MEK/ERK signalling were discovered in TK-RIG915 including an activating mutation in PIK3CA, upregulation of PDGFRA and AKT2, inactivating mutations in NF1, and a gain-of-function mutation in PTPN11. Additionally, deletion of CDKN2A/B, increased IDH1 expression, and decreased ARID1A expression were observed. Detection of phospho-S6, -4EBP1 and -ERK via immunohistochemistry confirmed PI3K pathway and ERK activation. Here, we report one of the first PDX models for RIG, which recapitulates the patient disease and is molecularly distinct from primary brain stem glioma. Genetic interrogation of this model has enabled the identification of potential therapeutic vulnerabilities in this currently incurable disease.","abstract":"Radiation-induced glioma (RIG) is a highly aggressive brain cancer arising as a consequence of radiation therapy. We report a case of RIG that arose in the brain stem following treatment for paediatric medulloblastoma, and the development and characterisation of a matched orthotopic patient-derived xenograft (PDX) model (TK-RIG915). Patient and PDX tumours were analysed using DNA methylation profiling, whole genome sequencing (WGS) and RNA sequencing. While initially thought to be a diffuse intrinsic pontine glioma (DIPG) based on disease location, results from methylation profiling and WGS were not consistent with this diagnosis. Furthermore, clustering analyses based on RNA expression suggested the tumours were distinct from primary DIPG. Additional gene expression analysis demonstrated concordance with a published RIG expression profile. Multiple genetic alterations that enhance PI3K/AKT and Ras/Raf/MEK/ERK signalling were discovered in TK-RIG915 including an activating mutation in PIK3CA, upregulation of PDGFRA and AKT2, inactivating mutations in NF1, and a gain-of-function mutation in PTPN11. Additionally, deletion of CDKN2A/B, increased IDH1 expression, and decreased ARID1A expression were observed. Detection of phospho-S6, -4EBP1 and -ERK via immunohistochemistry confirmed PI3K pathway and ERK activation. Here, we report one of the first PDX models for RIG, which recapitulates the patient disease and is molecularly distinct from primary brain stem glioma. Genetic interrogation of this model has enabled the identification of potential therapeutic vulnerabilities in this currently incurable disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-09T03:37:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004710","title":"Genome-wide somatic variants in CRC (GRCh38)","description":null,"abstract":"This dataset is and will be used in multiple upcoming publications. The dataset contains somatic variant calls in 344 whole-genome sequenced colorectal cancer samples and respective normals.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-09T12:28:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004711","title":"ATAC-Seq and CTCF ChIP-Seq on the OCIAML-2 cell line","description":null,"abstract":"ATAC-Seq and CTCF ChIP-Seq on the OCIAML-2 cell line","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004712","title":"Organoid_Derivation_Project___GRCh38___WGS","description":"Generation of normal and cancer organoids for sequencing as part of the WTSI-CRUK international collaboration with NCI (in HCMI) to generate the next generation of cancer cell lines","abstract":"Generation of normal and cancer organoids for sequencing as part of the WTSI-CRUK international collaboration with NCI (in HCMI) to generate the next generation of cancer cell lines","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-11T14:57:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004713","title":"Cancer_Cell_Line_Whole_Genome_Sequencing_5X","description":"5X Whole Genome Sequencing of the cancer cell lines used within the Cancer Dependency Map at Sanger to determine copy number.","abstract":"Whole genome sequencing of the cancer cell lines used within the Cancer Dependency Map at Sanger to determine copy number.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004714","title":"Transcriptome Sequencing Data of High Grade Serous Ovarian Cancer","description":null,"abstract":"Longitudinal transcriptome data to study chemoresponse in ovarian cancer. Includes over 200 samples from 61 patients. All patients have been treated with platinum-taxane based chemotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-12T07:58:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004715","title":"Ancestry COVID-19 study","description":null,"abstract":"The purpose of this study is to gain a deeper understanding of how different people respond to COVID-19. Our hope is that, through this knowledge, the pace of research into new preventive and therapeutic treatments for COVID-19 can be accelerated. This is accomplished by identifying a group of people who may have been exposed to, tested positive for, or recovered from COVID-19. Data will be shared with qualified external researchers working to develop preventative and therapeutic treatments for COVID-19. Before these data are shared, they will be de-identified (stripped of direct and indirect identifiers like name, place of birth, and so on) and aggregated with other data to protect the privacy of participants.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004716","title":"Ancestry COVID-19 study","description":"The purpose of this study is to gain a deeper understanding of how different people respond to COVID-19. Our hope is that, through this knowledge, the pace of research into new preventive and therapeutic treatments for COVID-19 and a better understanding of susceptibility and severity of the disease can be accelerated. This is accomplished by identifying a group of people who may have been exposed to, tested positive for, or recovered from COVID-19. Data will be shared with qualified external researchers working to develop preventive and therapeutic treatments for COVID-19. Before these data are shared, they will be de-identified (stripped of direct and indirect identifiers like name, place of birth, and so on) and aggregated with other data to protect the privacy of participants.","abstract":"The purpose of this study is to gain a deeper understanding of how different people respond to COVID-19. Our hope is that, through this knowledge, the pace of research into new preventive and therapeutic treatments for COVID-19 and a better understanding of susceptibility and severity of the disease can be accelerated. This is accomplished by identifying a group of people who may have been exposed to, tested positive for, or recovered from COVID-19. Data will be shared with qualified external researchers working to develop preventive and therapeutic treatments for COVID-19. Before these data are shared, they will be de-identified (stripped of direct and indirect identifiers like name, place of birth, and so on) and aggregated with other data to protect the privacy of participants.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001004717","title":"Single-cell RNA sequencing of bronchoalveolar lavages from COVID-19 patients","description":"Discriminating mild-moderate from critical COVID-19 disease by innate and adaptive immune single-cell profiling of bronchoalveolar lavages.","abstract":"Discriminating mild-moderate from critical COVID-19 disease by innate and adaptive immune single-cell profiling of bronchoalveolar lavages.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-13T08:52:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004718","title":"CAR_T_cell_Study","description":"CAR-T cell Study\n\nThe aim of this study is to understand single cell transcription and chromatin accessibility in CAR-T cells.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The aim of this study is to understand single cell transcription and chromatin accessibility in CAR-T cells.\n\nThe aim of this study is to understand single cell transcription and chromatin accessibility in CAR-T cells.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-13T13:11:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004719","title":"STAT5 is a therapeutically targetable vulnerability in cutaneous T-cell lymphoma","description":"Cutaneous T-cell lymphomas represent a heterogeneous group of lymphoproliferative disorders characterized by the infiltration and expansion of mature malignant T-cells into the skin. The disease encompasses distinct variants such as mycosis fungoides a skin resident variant, in which the malignant cells are restricted to skin lesions, and leukemic variant sézary syndrome characterized by circulating malignant T-cells. Here we integrated shallow whole genome sequencing and whole exome sequencing, on samples from four sézary syndrome patients and two advanced mycosis fungoides patients with blood involvement, to characterize genetic alterations and assess their therapeutic actionability. We identified an elevated copy number of 17q, resulting in increased STAT5 expression and activation, as a key factor in the pathophysiology of the disease.","abstract":"Cutaneous T-cell lymphomas represent a heterogeneous group of lymphoproliferative disorders characterized by the infiltration and expansion of mature malignant T-cells into the skin. The disease encompasses distinct variants such as mycosis fungoides a skin resident variant, in which the malignant cells are restricted to skin lesions, and leukemic variant sézary syndrome characterized by circulating malignant T-cells. Here we integrated shallow whole genome sequencing and whole exome sequencing, on samples from four sézary syndrome patients and two advanced mycosis fungoides patients with blood involvement, to characterize genetic alterations and assess their therapeutic actionability. We identified an elevated copy number of 17q, resulting in increased STAT5 expression and activation, as a key factor in the pathophysiology of the disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-13T17:36:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004720","title":"HCA_Gonads_Foetal_EU_H2020_HUGODECA_DNA","description":"Spatial analysis Fetal Gonads HUGODECA\n\nThe HUGODECA consortium brings together leading European academic and industrial experts (from 5 different EU countries). It includes active contributors and executives of the Human Cell Atlas (HCA) which will ensure complementarity with other ongoing HCA efforts. The overall HUGODECA concept is grounded on the integration of multiple synergistic expertise and technologies: Single cell profiling, spatial transcriptomic, 2D Mass cytometry and cyclic immunofluorescence and 3D imaging of optically cleared gonads. HUGODECA will implement novel tools, analytical and computational methods to process and integrate multidimensional OMICS and image data across different platforms. It will evaluate the accuracy of ex vivo culture models of human gonadal development and assess consequences of altering key signalling pathways.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Spatial analysis Fetal Gonads HUGODECA\n\nThe HUGODECA consortium brings together leading European academic and industrial experts (from 5 different EU countries). It includes active contributors and executives of the Human Cell Atlas (HCA) which will ensure complementarity with other ongoing HCA efforts. The overall HUGODECA concept is grounded on the integration of multiple synergistic expertise and technologies: Single cell profiling, spatial transcriptomic, 2D Mass cytometry and cyclic immunofluorescence and 3D imaging of optically cleared gonads. HUGODECA will implement novel tools, analytical and computational methods to process and integrate multidimensional OMICS and image data across different platforms. It will evaluate the accuracy of ex vivo culture models of human gonadal development and assess consequences of altering key signalling pathways.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004721","title":"_HCA_Uterine_Atlas_Endometriosis_sc","description":"HCA Uterine Atlas Endometriosis_sc\n\nEndometriosis is a chronic inflammatory disease driven by oestrogen, affecting around 10% of women of child-bearing again world-wide. It is described by the presence of endometrium-like tissue outside of the uterus (ectopic endometriosis tissue) and debilitating chronic pain. There is a lack of understanding of endometriosis pathogenesis, as well as cellular composition of both the eutopic endometrium and ectopic endometriosis tissue of endometriosis patients.There are therefore two main aims for this study. Using single cell genomics and spatial methods we aim to: \nI)\tcharacterise endometrial cellular census in women with and without endometriosis \nII)\tcharacterise cellular census of ectopic endometriosis tissue\n \nFurthermore, we aim to establish endometrial organoids and endometriosis organoids from the samples collected and characterise these using single cell genomics and spatial methods.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"HCA Uterine Atlas Endometriosis_sc\n\nEndometriosis is a chronic inflammatory disease driven by oestrogen, affecting around 10% of women of child-bearing again world-wide. It is described by the presence of endometrium-like tissue outside of the uterus (ectopic endometriosis tissue) and debilitating chronic pain. There is a lack of understanding of endometriosis pathogenesis, as well as cellular composition of both the eutopic endometrium and ectopic endometriosis tissue of endometriosis patients.There are therefore two main aims for this study. Using single cell genomics and spatial methods we aim to: \nI)\tcharacterise endometrial cellular census in women with and without endometriosis \nII)\tcharacterise cellular census of ectopic endometriosis tissue\n \nFurthermore, we aim to establish endometrial organoids and endometriosis organoids from the samples collected and characterise these using single cell genomics and spatial methods.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004722","title":"HCA_Placental_Infection_Atlas","description":"HCA Placental Infection Atlas\n\nSelf-renewing human trophoblast stem cells (hTSC) can give rise to major trophoblast lineages, including syncytiotrophoblast (SCT) and extravillous trophoblast (EVT). hTSC has facilitated the study of placental development and function in vitro. Here, we aim to utilise the hTSC line (HMDMC 20/0005) to study human placental infection and inflammation. This study will provide the opportunity to better understand the pathogenesis of human placenta in the event of infection and inflammation. In brief, differentiated hTSC will be infected with relevant pathogens and stimulated with a panel of inflammatory cytokines. We will use single-cell genomic and spatial approaches to characterise cellular heterogeneity in response to infection or cytokines stimulus. In parallel, we will investigate the interaction between iPSC-derived macrophages with different trophoblast lineages during the course of infection using single-cell genomic and spatial methods.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"HCA Placental Infection Atlas\n\nSelf-renewing human trophoblast stem cells (hTSC) can give rise to major trophoblast lineages, including syncytiotrophoblast (SCT) and extravillous trophoblast (EVT). hTSC has facilitated the study of placental development and function in vitro. Here, we aim to utilise the hTSC line (HMDMC 20/0005) to study human placental infection and inflammation. This study will provide the opportunity to better understand the pathogenesis of human placenta in the event of infection and inflammation. In brief, differentiated hTSC will be infected with relevant pathogens and stimulated with a panel of inflammatory cytokines. We will use single-cell genomic and spatial approaches to characterise cellular heterogeneity in response to infection or cytokines stimulus. In parallel, we will investigate the interaction between iPSC-derived macrophages with different trophoblast lineages during the course of infection using single-cell genomic and spatial methods.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-14T10:17:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004723","title":"HCA_Gonads_Foetal_EU_H2020_HUGODECA_RNA","description":"Cell Atlas of human fetal gonads\n\nThe HUGODECA consortium brings together leading European academic and industrial experts (from 5 different EU countries). It includes active contributors and executives of the Human Cell Atlas (HCA) which will ensure complementarity with other ongoing HCA efforts. The overall HUGODECA concept is grounded on the integration of multiple synergistic expertise and technologies: Single cell profiling, spatial transcriptomic, 2D Mass cytometry and cyclic immunofluorescence and 3D imaging of optically cleared gonads. HUGODECA will implement novel tools, analytical and computational methods to process and integrate multidimensional OMICS and image data across different platforms. It will evaluate the accuracy of ex vivo culture models of human gonadal development and assess consequences of altering key signalling pathways.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Cell Atlas of human fetal gonads\n\nThe HUGODECA consortium brings together leading European academic and industrial experts (from 5 different EU countries). It includes active contributors and executives of the Human Cell Atlas (HCA) which will ensure complementarity with other ongoing HCA efforts. The overall HUGODECA concept is grounded on the integration of multiple synergistic expertise and technologies: Single cell profiling, spatial transcriptomic, 2D Mass cytometry and cyclic immunofluorescence and 3D imaging of optically cleared gonads. HUGODECA will implement novel tools, analytical and computational methods to process and integrate multidimensional OMICS and image data across different platforms. It will evaluate the accuracy of ex vivo culture models of human gonadal development and assess consequences of altering key signalling pathways.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":[35794482],"external_links":null,"is_released":true,"released_date":"2020-10-14T10:28:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004724","title":"Multiomics Characterization of Low-grade Serous Ovarian Carcinoma","description":"Low-grade serous ovarian carcinoma (LGSOC) is a rare tumor subtype with high case fatality rates. There is a pressing need to develop effective treatments using newly available preclinical models for therapeutic discovery and drug evaluation. In this study, we use multiomics integration of whole exome sequencing, RNA sequencing, and mass spectrometry-based proteomics on fourteen LGSOC patient derived cell lines to elucidate novel biomarkers and therapeutic vulnerabilities.","abstract":"Low-grade serous ovarian carcinoma (LGSOC) is a rare tumor subtype with high case fatality rates. There is a pressing need to develop effective treatments using newly available preclinical models for therapeutic discovery and drug evaluation. In this study, we use multiomics integration of whole exome sequencing, RNA sequencing, and mass spectrometry-based proteomics on fourteen LGSOC patient derived cell lines to elucidate novel biomarkers and therapeutic vulnerabilities.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-14T10:28:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004725","title":"Uterine_Atlas_Endometriosis","description":"Uterine Atlas Endometriosis\n\nEndometriosis is a chronic inflammatory disease driven by oestrogen, affecting around 10% of women of child-bearing again world-wide. It is described by the presence of endometrium-like tissue outside of the uterus (ectopic endometriosis tissue) and debilitating chronic pain. There is a lack of understanding of endometriosis pathogenesis, as well as cellular composition of both the eutopic endometrium and ectopic endometriosis tissue of endometriosis patients.There are therefore two main aims for this study. Using single cell genomics and spatial methods we aim to: \nI)\tcharacterise endometrial cellular census in women with and without endometriosis \nII)\tcharacterise cellular census of ectopic endometriosis tissue\n \nFurthermore, we aim to establish endometrial organoids and endometriosis organoids from the samples collected and characterise these using single cell genomics and spatial methods.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Uterine Atlas Endometriosis\n\nEndometriosis is a chronic inflammatory disease driven by oestrogen, affecting around 10% of women of child-bearing again world-wide. It is described by the presence of endometrium-like tissue outside of the uterus (ectopic endometriosis tissue) and debilitating chronic pain. There is a lack of understanding of endometriosis pathogenesis, as well as cellular composition of both the eutopic endometrium and ectopic endometriosis tissue of endometriosis patients.There are therefore two main aims for this study. Using single cell genomics and spatial methods we aim to: \nI)\tcharacterise endometrial cellular census in women with and without endometriosis \nII)\tcharacterise cellular census of ectopic endometriosis tissue\n \nFurthermore, we aim to establish endometrial organoids and endometriosis organoids from the samples collected and characterise these using single cell genomics and spatial methods.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-14T11:18:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004726","title":"HCA_Uterine_Atlas_Endometriosis_spatial","description":"HCA Endometrium HUTER_spatial\n\nEndometriosis is a chronic inflammatory disease driven by oestrogen, affecting around 10% of women of child-bearing again world-wide. It is described by the presence of endometrium-like tissue outside of the uterus (ectopic endometriosis tissue) and debilitating chronic pain. There is a lack of understanding of endometriosis pathogenesis, as well as cellular composition of both the eutopic endometrium and ectopic endometriosis tissue of endometriosis patients.There are therefore two main aims for this study. Using single cell genomics and spatial methods we aim to: \nI)\tcharacterise endometrial cellular census in women with and without endometriosis \nII)\tcharacterise cellular census of ectopic endometriosis tissue\n \nFurthermore, we aim to establish endometrial organoids and endometriosis organoids from the samples collected and characterise these using single cell genomics and spatial methods.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"HCA Endometrium HUTER_spatial\n\nEndometriosis is a chronic inflammatory disease driven by oestrogen, affecting around 10% of women of child-bearing again world-wide. It is described by the presence of endometrium-like tissue outside of the uterus (ectopic endometriosis tissue) and debilitating chronic pain. There is a lack of understanding of endometriosis pathogenesis, as well as cellular composition of both the eutopic endometrium and ectopic endometriosis tissue of endometriosis patients.There are therefore two main aims for this study. Using single cell genomics and spatial methods we aim to: \nI)\tcharacterise endometrial cellular census in women with and without endometriosis \nII)\tcharacterise cellular census of ectopic endometriosis tissue\n \nFurthermore, we aim to establish endometrial organoids and endometriosis organoids from the samples collected and characterise these using single cell genomics and spatial methods.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004727","title":"HCA_Female_Reproductive_Adult_WSSS_RNA","description":"HCA Endometrium_LM\n\nThe endometrium regenerates monthly and its transformation is executed through dynamic changes in states and interactions of multiple cell types. Using transcriptomics methods we seek to profile changes of the endometrium across the menstrual cycle. Our map will have implications in women’s health and cancer, by enabling the interpretation of GWAS analyses or the studying functional consequences of somatic mutations.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"HCA Endometrium_LM\n\nThe endometrium regenerates monthly and its transformation is executed through dynamic changes in states and interactions of multiple cell types. Using transcriptomics methods we seek to profile changes of the endometrium across the menstrual cycle. Our map will have implications in women’s health and cancer, by enabling the interpretation of GWAS analyses or the studying functional consequences of somatic mutations.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-14T11:29:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004728","title":"Microbiota 16S sequencing study in NSCLC patients eligible for surgery without neoadjuvant treatment","description":"18 non-small cell lung cancer patients eligible for surgery without neaodjuvant treatment were included in the study at Centre Jean Perrin (France). Patients did not take any antibiotics, food supplements or immunostimulants 2 months prior to inclusion. During surgery, patients underwent partial or complete lobectomy where samples of non-malignant lung tissue, peritumoural tissue and tumour were resected from the removed lobe. This was preceeded by the washing of the removed lobe and obtaining the broncho-alveolar lavage fluid. These four sample types were analysed by 16S sequencing in 17 from 18 patients.\nThe study is a part of the project \"Characterization of Microbiota (Intestinal, From Lungs, and Upper Airways) in Patients With Non-small Cell Lung Carcinoma: Exploratory Study \" which is registered under ref. NCT03068663 (clinicaltrials.gov).","abstract":"18 non-small cell lung cancer patients eligible for surgery without neaodjuvant treatment were included in the study at Centre Jean Perrin (France). Patients did not take any antibiotics, food supplements or immunostimulants 2 months prior to inclusion. During surgery, patients underwent partial or complete lobectomy where samples of non-malignant lung tissue, peritumoural tissue and tumour were resected from the removed lobe. This was preceeded by the washing of the removed lobe and obtaining the broncho-alveolar lavage fluid. These four sample types were analysed by 16S sequencing in 17 from 18 patients.\nThe study is a part of the project \"Characterization of Microbiota (Intestinal, From Lungs, and Upper Airways) in Patients With Non-small Cell Lung Carcinoma: Exploratory Study \" which is registered under ref. NCT03068663 (clinicaltrials.gov).","study_type":"Other","pubmed_ids":[32450847],"external_links":null,"is_released":true,"released_date":"2020-10-15T08:08:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004729","title":"Multi Omics of glioma in the the Chinese Glioma Genome Atlas (CGGA) project","description":null,"abstract":"Glioma is the most common and aggressive brain cancer in adults. While primary glioma has been widely studied, molecular characterization of recurrent glioma is still rare. The high-quality sequencing data that we generated provides a useful resource for the community. The CGGA project contains over 2,000 samples from Chinese cohorts. It totally includes the whole-exome sequencing (286), DNA methylation (159), mRNA sequencing (1,018), mRNA microarray (301) and microRNA microarray (198) and matched clinical data. CGGA removes the barriers to researchers, providing rapid and convenient access to high-quality functional genomic data resources for biological research and clinical applications.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-15T10:17:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004730","title":"HCA_Skin_Adult_WSSS_RNA_KCL","description":"WSSS Deep Dive Healthy human adult skin. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/\n\nWSSS Deep Dive Healthy human adult skin: The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions.","abstract":"WSSS Deep Dive Healthy human adult skin. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/\n\nWSSS Deep Dive Healthy human adult skin: The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004731","title":"HCA_Kidney_Adult_WSSS_RNA","description":"Defining regional anatomical variation in cellular composition, transcriptome and epigenome in the human kidney\n\nThe kidneys play a critical role in homeostasis, excreting waste and acid and maintaining electrolyte and water balance. The homeostatic function of the kidney generates substantial differences in tissue environment between different anatomical regions of the kidney. Complementing efforts in generating single-cell molecular profiles across the entire cross-section of the adult human kidney, from outer cortex to upper ureter, we aim to also interrogate whether the epigenome of kidney-resident immune cells varies across different anatomical regions of the kidney. The expression of RNA transcripts is, in part, controlled by the state of chromatin, with closed structures sterically hindering the binding of transcriptional modulators. The chromatin landscape of immune cells can change according to environmental stimuli, for example, via engagement of toll-like receptor (TLR)4 with lipopolysaccharide. Here we wish to determine whether and how the environmental differences in cortex, medulla and pelvis might impact resident immune cell epigenome using single-cell ATAC-seq on the 10x platform\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Defining regional anatomical variation in cellular composition, transcriptome and epigenome in the human kidney\n\nThe kidneys play a critical role in homeostasis, excreting waste and acid and maintaining electrolyte and water balance. The homeostatic function of the kidney generates substantial differences in tissue environment between different anatomical regions of the kidney. Complementing efforts in generating single-cell molecular profiles across the entire cross-section of the adult human kidney, from outer cortex to upper ureter, we aim to also interrogate whether the epigenome of kidney-resident immune cells varies across different anatomical regions of the kidney. The expression of RNA transcripts is, in part, controlled by the state of chromatin, with closed structures sterically hindering the binding of transcriptional modulators. The chromatin landscape of immune cells can change according to environmental stimuli, for example, via engagement of toll-like receptor (TLR)4 with lipopolysaccharide. Here we wish to determine whether and how the environmental differences in cortex, medulla and pelvis might impact resident immune cell epigenome using single-cell ATAC-seq on the 10x platform\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-15T14:40:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004732","title":"HCA_Lung_Adult_discovAIR_RNA","description":"Deep Dive for Adult Lung\n\nHCA deep dive human adult Lung: The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells in the adult human lung. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Deep Dive for Adult Lung\n\nHCA deep dive human adult Lung: The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells in the adult human lung. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004733","title":"Mutational Landscape and Tumor Burden Assessed by Cell-Free DNA in Diffuse Large B-Cell Lymphoma: a Population-based Study","description":"Purpose: We analyzed the utility of cfDNA in a prospective population-based cohort to determine the mutational profile, assess tumor burden, and estimate its impact in response rate and outcome in patients with DLBCL.\nExperimental Design: One-hundred patients were diagnosed with DLBCL during the study period. Mutational status of 112 genes was studied in cfDNA by targeted next-generation sequencing. Paired formalin-fixed paraffin-embedded samples and volumetric PET/CT were assessed when available. \nResults: Appropriate cfDNA to perform the analyses was obtained in 79/100 cases. At least one mutation could be detected in 69/79 cases (87%). The sensitivity of cfDNA to detect the mutations was 68% (95% CI: 56.2-78.7). The mutational landscape found in cfDNA samples was highly consistent with that shown in the tissue and allowed genetic classification in 43% of the cases. A higher amount of ctDNA significantly correlated with clinical parameters related to tumor burden (elevated LDH and β2-microglobulin serum levels, advanced stage, and high-risk IPI) and total metabolic tumor volume assessed by PET/CT. In patients treated with curative intent, high ctDNA levels (&amp;gt;2.5 log hGE/mL) were associated with lower complete response (65% vs. 96%, P&amp;lt;0.004), shorter progression-free survival (65% vs. 85%, P=0.038) and overall survival (73% vs. 100%, P=0.007) at 2 years, although it did not maintain prognostic value in multivariate analyses. \nConclusions: In a population-based prospective DLBCL series, cfDNA resulted an alternative source to estimate tumor burden and to determine the tumor mutational profile and genetic classification, which have prognostic implications and may contribute to a future tailored","abstract":"Purpose: We analyzed the utility of cfDNA in a prospective population-based cohort to determine the mutational profile, assess tumor burden, and estimate its impact in response rate and outcome in patients with DLBCL.\nExperimental Design: One-hundred patients were diagnosed with DLBCL during the study period. Mutational status of 112 genes was studied in cfDNA by targeted next-generation sequencing. Paired formalin-fixed paraffin-embedded samples and volumetric PET/CT were assessed when available. \nResults: Appropriate cfDNA to perform the analyses was obtained in 79/100 cases. At least one mutation could be detected in 69/79 cases (87%). The sensitivity of cfDNA to detect the mutations was 68% (95% CI: 56.2-78.7). The mutational landscape found in cfDNA samples was highly consistent with that shown in the tissue and allowed genetic classification in 43% of the cases. A higher amount of ctDNA significantly correlated with clinical parameters related to tumor burden (elevated LDH and β2-microglobulin serum levels, advanced stage, and high-risk IPI) and total metabolic tumor volume assessed by PET/CT. In patients treated with curative intent, high ctDNA levels (&amp;gt;2.5 log hGE/mL) were associated with lower complete response (65% vs. 96%, P&amp;lt;0.004), shorter progression-free survival (65% vs. 85%, P=0.038) and overall survival (73% vs. 100%, P=0.007) at 2 years, although it did not maintain prognostic value in multivariate analyses. \nConclusions: In a population-based prospective DLBCL series, cfDNA resulted an alternative source to estimate tumor burden and to determine the tumor mutational profile and genetic classification, which have prognostic implications and may contribute to a future tailored","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-16T09:09:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004734","title":"Identification of rare germline variants in familial multiple myeloma","description":"The risk of developing multiple myeloma (MM) in first-degree relatives of affected individuals is 2 to 4 fold higher than in the general population, implying the existence of inherited susceptibility. While over 20 common, low-penetrance variants have been associated with MM risk, less is known about rare, high-penetrance germline predisposition. We aimed to identify and characterize high/moderated penetrance germline variants in MM families using whole genome sequencing. For that purpose we identified families with at least two individuals diagnosed with MM or its precursors MGUS and smoldering MM. Also, patients with solitary plasmacytoma and AL amyloidosis were enrolled. We also recruited unaffected family members, and they were screened to exclude undetected MM or its precursor stages. After whole genome sequencing of blood DNA and filtering for rare variants (minor allele frequency &lt;0.1%) and family segregation, variants are prioritized by a range of published in silico tools and literature search. The most promising variants are subjected to experimental validation to evaluate their functional relevance. Our data will provide guidance to worldwide efforts to unravel germline predisposition in MM and validation of the proposed variants and genes.","abstract":"The risk of developing multiple myeloma (MM) in first-degree relatives of affected individuals is 2 to 4 fold higher than in the general population, implying the existence of inherited susceptibility. While over 20 common, low-penetrance variants have been associated with MM risk, less is known about rare, high-penetrance germline predisposition. We aimed to identify and characterize high/moderated penetrance germline variants in MM families using whole genome sequencing. For that purpose we identified families with at least two individuals diagnosed with MM or its precursors MGUS and smoldering MM. Also, patients with solitary plasmacytoma and AL amyloidosis were enrolled. We also recruited unaffected family members, and they were screened to exclude undetected MM or its precursor stages. After whole genome sequencing of blood DNA and filtering for rare variants (minor allele frequency &lt;0.1%) and family segregation, variants are prioritized by a range of published in silico tools and literature search. The most promising variants are subjected to experimental validation to evaluate their functional relevance. Our data will provide guidance to worldwide efforts to unravel germline predisposition in MM and validation of the proposed variants and genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-16T09:23:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004735","title":"Multi-region whole-exome sequencing of 10 neuroblastoma cases","description":"To investigate intratumour heterogeneity and to better understand tumour evolution in neuroblastoma, we have performed a multi-region whole-exome sequencing on a total of 51 spatially separated tumor samples from 9 primary neuroblastomas (2 low-risk, 1 intermediate-risk and 6 high-risk) and 1 relapsed neuroblastoma. We also assessed the impact of chemotherapy on the clonal expansion by sequencing tumour regions from one medium risk and one  high-risk tumour for which we had matched samples obtained at diagnosis and after chemotherapy.","abstract":"To investigate intratumour heterogeneity and to better understand tumour evolution in neuroblastoma, we have performed a multi-region whole-exome sequencing on a total of 51 spatially separated tumor samples from 9 primary neuroblastomas (2 low-risk, 1 intermediate-risk and 6 high-risk) and 1 relapsed neuroblastoma. We also assessed the impact of chemotherapy on the clonal expansion by sequencing tumour regions from one medium risk and one  high-risk tumour for which we had matched samples obtained at diagnosis and after chemotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-16T09:55:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004736","title":"Study of tumor RNA expression differences between treated and untreated PitNET patients","description":"The goal of the study is to evaluate response of PitNET to drug therapy before surgery. Patients with and without drug therapy are compared in RNA level. The RNA is extracted from surgery material, sequenced and deferentially expressed genes (DEG) determined.","abstract":"The goal of the study is to evaluate response of PitNET to drug therapy before surgery. Patients with and without drug therapy are compared in RNA level. The RNA is extracted from surgery material, sequenced and deferentially expressed genes (DEG) determined.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-16T14:26:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004737","title":"Genetic study in DNA derived from aged mouse bone marrow","description":"To evaluate the prevalence of the clonal hematopoiesis in mice, we performed single colony whole-genome sequencing of hematopoietic stem cells and error-corrected targeted sequencing in aged mice.","abstract":"To evaluate the prevalence of the clonal hematopoiesis in mice, we performed single colony whole-genome sequencing of hematopoietic stem cells and error-corrected targeted sequencing in aged mice.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004738","title":"CD3+ T cells ind liver and mesenteric fat in NAFLD and NASH","description":null,"abstract":"Single cell RNA seq data from liver and adipose tissue T cells originating in individuals diagnosed with NAFLD and NASH. Data include 2 patient samples for each tissue, for a total of 4 samples.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004739","title":"Prognostic and therapeutic significance of leukemia subtypes and minimal residual disease measurements in pediatric acute lymphoblastic leukemia treated with contemporary risk-directed trial: a cohort study","description":"Background Genomic analyses to identify leukemia subtypes and refinement of minimal residual disease (MRD) determination are two recent advances that would have substantial impact on the management of children with acute lymphoblastic leukemia (ALL). However, the combined application of these two approaches to determine the prognostic and therapeutic significance of MRD measurement and full spectrum of leukemia subtypes in the context of contemporary risk-directed therapy has not been studied comprehensively.MethodsBetween October 29, 2007 and March 26, 2017, 598 consecutive children with newly diagnosed ALL were enrolled in a clinical trial at St. Jude Children’s Research Hospital. Patients were provisional classified according to the presenting clinical and laboratory features including immunophenotype and cytogenetics. Patients with ETV6-RUNX1 and high hyperdiploid B-progenitor ALL were provisionally included in the low-risk groups; those with TCF3-PBX1, hypodiploidy and T-cell ALL in the standard (intermediate)-risk group; and patients with BCR-ABL1, KMT2A and early T-cell precursor ALL in the high-risk group. Final risk assignment was based primarily on MRD levels measured by flow cytometry on Day 15 (≥1%) and Day 42 (&lt;0.01% or ≥1%) of remission induction. Using genomic classification based on cytogenetics and genomic analysis (single nucleotide polymorphism array analysis and transcriptome, exome, and genome sequencing), patients were classified into 17 subtypes. The primary aim was to determine the event-free survival, overall survival and cumulative risk of relapse according to specific leukemia subtypes and MRD levels on Days 8, 15 and 42 of remission induction. This clinical trial was registered at ClinicalTrials.gov, number NCT00549848.FindingsPatients with ETV6-RUNX1, high hyperdiploidy and DUX4-rearranged B-ALL all received low- or standard-risk therapy, and had the highest 5-year event-free survival rates: 98.4% (95% CI, 95.9-100), 95.3% (91.2-99.4), and 95.0% (84.2-100), respectively. All 142 patients with Day 8 MRD&lt;0.01%, except two with KMT2A-rearranged ALL and one with TCF3-PBX1, were in continuous complete remission. The TCF3-PBX1, PAX5alt, T-cell, early T-cell precursor, iAMP21 and hypodiploid ALL had intermediate outcome with 5-year event-free survival rates ranging from 80.0% (39.4-100) to 88.2% (71.7-100). Patients with KMT2A-rearranged, BCR-ABL1, BCR-ABL1-like and ETV6-RUNX1-like ALL had the worst outcomes, with 5-year event-free survival rates between 64.1% (43.9-84.3) and 76.2% (51.9-100), despite most patients receiving standard- or high-risk therapy. Treatment intensification based on MRD and genotype improved outcome. Relapse did not occur in any of the patients with ETV6-RUNX1, DUX4-rearranged, TCF3-PBX1, iAMP21, ZNF384-rearranged, hypodiploid, or BCR-ABL1-like B-ALL who had day 15 MRD≥1% and received standard-risk therapy.  However, day 42 MRD&lt;0.01% did not preclude relapse in patients with intermediate-risk or unfavorable subtypes including TCF3-PBX1, PAX5alt, T-cell, iAMP21, BCR-ABL1, BCR-ABL1-like, ETV6-RUNX1-like, KMT2A-rearranged, and MEF2D-rearranged ALL, despite intensified treatment in the standard- or high-risk arms. InterpretationContemporary risk-directed treatment based on genotypes and MRD can cure virtually all patients with ETV6-RUNX1, hyperdiploid&gt;50 and DUX4-rearranged ALL. While intensified treatment improve outcome for patients with high MRD during induction, substantial proportions of patients with intermediate-risk or unfavorable subtypes would still relapse even achieving negative MRD status at the end of induction and require novel therapeutics to improve outcome.","abstract":"Background Genomic analyses to identify leukemia subtypes and refinement of minimal residual disease (MRD) determination are two recent advances that would have substantial impact on the management of children with acute lymphoblastic leukemia (ALL). However, the combined application of these two approaches to determine the prognostic and therapeutic significance of MRD measurement and full spectrum of leukemia subtypes in the context of contemporary risk-directed therapy has not been studied comprehensively.MethodsBetween October 29, 2007 and March 26, 2017, 598 consecutive children with newly diagnosed ALL were enrolled in a clinical trial at St. Jude Children’s Research Hospital. Patients were provisional classified according to the presenting clinical and laboratory features including immunophenotype and cytogenetics. Patients with ETV6-RUNX1 and high hyperdiploid B-progenitor ALL were provisionally included in the low-risk groups; those with TCF3-PBX1, hypodiploidy and T-cell ALL in the standard (intermediate)-risk group; and patients with BCR-ABL1, KMT2A and early T-cell precursor ALL in the high-risk group. Final risk assignment was based primarily on MRD levels measured by flow cytometry on Day 15 (≥1%) and Day 42 (&lt;0.01% or ≥1%) of remission induction. Using genomic classification based on cytogenetics and genomic analysis (single nucleotide polymorphism array analysis and transcriptome, exome, and genome sequencing), patients were classified into 17 subtypes. The primary aim was to determine the event-free survival, overall survival and cumulative risk of relapse according to specific leukemia subtypes and MRD levels on Days 8, 15 and 42 of remission induction. This clinical trial was registered at ClinicalTrials.gov, number NCT00549848.FindingsPatients with ETV6-RUNX1, high hyperdiploidy and DUX4-rearranged B-ALL all received low- or standard-risk therapy, and had the highest 5-year event-free survival rates: 98.4% (95% CI, 95.9-100), 95.3% (91.2-99.4), and 95.0% (84.2-100), respectively. All 142 patients with Day 8 MRD&lt;0.01%, except two with KMT2A-rearranged ALL and one with TCF3-PBX1, were in continuous complete remission. The TCF3-PBX1, PAX5alt, T-cell, early T-cell precursor, iAMP21 and hypodiploid ALL had intermediate outcome with 5-year event-free survival rates ranging from 80.0% (39.4-100) to 88.2% (71.7-100). Patients with KMT2A-rearranged, BCR-ABL1, BCR-ABL1-like and ETV6-RUNX1-like ALL had the worst outcomes, with 5-year event-free survival rates between 64.1% (43.9-84.3) and 76.2% (51.9-100), despite most patients receiving standard- or high-risk therapy. Treatment intensification based on MRD and genotype improved outcome. Relapse did not occur in any of the patients with ETV6-RUNX1, DUX4-rearranged, TCF3-PBX1, iAMP21, ZNF384-rearranged, hypodiploid, or BCR-ABL1-like B-ALL who had day 15 MRD≥1% and received standard-risk therapy.  However, day 42 MRD&lt;0.01% did not preclude relapse in patients with intermediate-risk or unfavorable subtypes including TCF3-PBX1, PAX5alt, T-cell, iAMP21, BCR-ABL1, BCR-ABL1-like, ETV6-RUNX1-like, KMT2A-rearranged, and MEF2D-rearranged ALL, despite intensified treatment in the standard- or high-risk arms. InterpretationContemporary risk-directed treatment based on genotypes and MRD can cure virtually all patients with ETV6-RUNX1, hyperdiploid&gt;50 and DUX4-rearranged ALL. While intensified treatment improve outcome for patients with high MRD during induction, substantial proportions of patients with intermediate-risk or unfavorable subtypes would still relapse even achieving negative MRD status at the end of induction and require novel therapeutics to improve outcome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-16T19:45:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004740","title":"Single Cell ATAC-Seq on human cord-blood derived HSPC.","description":null,"abstract":"Cells from three sorted CD34+/CD38+ and three sorted CD34+/CD38-CD45RA- human cord-blood-derived HSPC samples were processed on the 10X Genomics single cell ATAC-seq platform.  Additionally scATAC-Seq was performed upon human cord-blood derived GFP+/CD34+/CD38-/CD45RA- cells harbouring shCTCF and equivalently sorted cells harbouring shCtrl purified from mouse xenografts at 4 weeks post-transplantation. \nSamples uploaded in bam format, aligned to hg19 with the following additional fields (as per 10x format):\nCB\tZ\tChromium cellular barcode sequence that is error-corrected and confirmed against a list of known-good barcode sequences.\nCR\tZ\tChromium cellular barcode sequence as reported by the sequencer.\nCY\tZ\tChromium cellular barcode read quality. Phred scores as reported by sequencer.\nBC\tZ\tSample index read.\nQT\tZ\tSample index read quality. Phred scores as reported by sequencer.\nTR\tZ\tAdapter sequence trimmed off the end of the read.\nTQ\tZ\tBase quality for the trimmed adapater sequence. Phred scores as reported by sequencer.\nGP\ti\tGenome position. Note: this is an auxiliary tag used for the purpose of duplicate marking and is not intended for downstream use. We intend to deprecate this tag in subsequent versions.\nMP\ti\tGenome position of mate-pair. Note: this is an auxiliary tag used for the purpose of duplicate marking and is not intended for downstream use. We intend to deprecate this tag in subsequent versions.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-16T20:31:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004741","title":"ATAC-Seq and CTCF ChIP-Seq on the OCIAML-2 cell line","description":null,"abstract":"ATAC-Seq and CTCF ChIP-Seq on the OCIAML-2 cell line","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-16T20:31:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004742","title":"Bulk ATAC-Seq on sorted cord blood hematopoietic populations","description":null,"abstract":"Bulk ATAC-Seq was performed on human cord-blood derived hematopoietis popuations using the following markers:\n\nLT-HSC; CD34+CD38-CD45RA-CD90+CD49f+\nST-HSC; CD34+CD38-CD45RA-CD90-CD49f-\nMLP; CD34+CD38-CD45RA+\nCMP; CD34+CD38+ CD10-CD45RA-Flt3+CD71-\nGMP; CD34+CD38+ CD10-CD45RA+ CD71-\nMEP; CD34+CD38+ CD10-CD45RA-Flt3-CD71+\nT cell; CD3+CD19-\nB cell; CD19+CD3-\nNK cell; CD56+CD3-CD19-CD14-\nGranulocyte; CD14+CD15+CD3-CD19-\nMonocyte; CD14+CD15-CD3-CD19-\nDC; CD11c+CD45+\nErythroid cell; CD71+GPA+","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-16T20:31:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004743","title":"Hi-C on the OCIAML-2 Cell Line","description":null,"abstract":"2.5M OCI-AML2 cells per replicate according to previously reported protocol (Rao et al. 2014) with DPNII as a restriction enzyme. Libraries  were sequenced using the NextSeq (Illumina) to generate paired-end 150-bp reads. Reads from 6 separate Hi-C replicates, were pooled together.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-16T20:31:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004744","title":"Low-C on Human CB-derived LT-HSC and ST-HSC","description":null,"abstract":"Low-C was performed upon human cord-blood long-term hematopoietic stem cells (LT-HSC) and short-term hematopoietic stem cells (ST-HSC). This was used to demonstrate that chromatin conformation changes associated with LT-HSC activation are enriched in ST-HSC.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-16T20:31:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004745","title":"RNA_Seq on Human CB-derived LT-HSC with shCTCF or control vector","description":null,"abstract":"RNA-Seq on human cord-blood derived LT-HSC transduced with shCTCF  or LacZ Control 3 days post transduction","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-16T20:31:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004746","title":"Extramammary Paget Disease","description":"In order to clarify the mutational landscape of Extramammary Paget disease, we performed exome-sequencing of surgical samples and target-sequencing of formalin-fixed, paraffin-embedded tissues.","abstract":"In order to clarify the mutational landscape of Extramammary Paget disease, we performed exome-sequencing of surgical samples and target-sequencing of formalin-fixed, paraffin-embedded tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-19T06:38:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004747","title":"Small molecule screen reveals synergy of cell cycle checkpoint kinase inhibitors with DNA-damaging chemotherapies in medulloblastoma (methylation & RNAseq dataset)","description":null,"abstract":"This study utilised a range of different Group 3 subtype II and SHH-alpha models of medulloblastoma. Illumina methylation arrays were performed on all models. Most have already been published as cited in the manuscript, but data for those unpublished previously are reported here.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004748","title":"Small molecule screen reveals synergy of cell cycle checkpoint kinase inhibitors with DNA-damaging chemotherapies in medulloblastoma (RNAseq dataset)","description":null,"abstract":"This study utilised a range of different Group 3 subtype II and SHH-alpha models of medulloblastoma. RNAseq was performed on all models. Most have already been published as cited in the manuscript, but data for those unpublished previously are reported here.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-19T09:51:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004749","title":"DIPG RNA and exome sequencing","description":"DIPG is a paediatric high-grade glioma that diffusely infiltrates the brainstem and is the leading cause of paediatric brain tumour death. Here we performed RNA and whole exome sequencing on DIPG and control samples to analyse transcriptomic and genetic alterations associated with this devastating disease, and to understand the relationship between them.","abstract":"DIPG is a paediatric high-grade glioma that diffusely infiltrates the brainstem and is the leading cause of paediatric brain tumour death. Here we performed RNA and whole exome sequencing on DIPG and control samples to analyse transcriptomic and genetic alterations associated with this devastating disease, and to understand the relationship between them.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-19T10:43:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004750","title":"The evolution of adult T-cell acute lymphoblastic leukemia","description":"We profile the whole-genome of 19 primary T-ALLs from adult patients and the corresponding relapse malignancies.  Concretely, samples were taken at the time of diagnosis (primary), at time of remission (used as control) and at recurrence of the malignancy after treatment (relapse). The libraries were sequenced on HiSeq 4000 or NovaSeq 6000 (Illumina) with a paired-end read length of 2x151bp.","abstract":"We profile the whole-genome of 19 primary T-ALLs from adult patients and the corresponding relapse malignancies.  Concretely, samples were taken at the time of diagnosis (primary), at time of remission (used as control) and at recurrence of the malignancy after treatment (relapse). The libraries were sequenced on HiSeq 4000 or NovaSeq 6000 (Illumina) with a paired-end read length of 2x151bp.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-19T12:56:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004751","title":"Characterization of T cell tumor infiltration in brain metastases through the analysis of the cerebrospinal fluid","description":null,"abstract":"Brain metastases are the most common tumor of the brain with a dismal prognosis. A fraction of patients with brain metastasis benefit from the treatment with immune checkpoint inhibitors (ICI) and tumor inflammation has been used as a biomarker to predict response. However, the anatomical location of brain lesions limits the access to tumor material to determine inflammation rates. We have characterized immune cells present in brain lesions and matched cerebrospinal fluids (CSF), applying single-cell RNA  sequencing combined with T cell receptor genotyping. We observed tumor inflammation and CD8​ + ​ T cell infiltration to be recapitulated in the CSF. Consistently, identical T cell receptor clonotypes were detected in brain lesions and CSF, confirming the cell exchange of both compartments. We propose the analysis of immune cells of the CSF to present a non-invasive profiling alternative of brain metastases inflammation states for ICI response prediction and clonotype detection for cell therapy.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-19T17:24:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004752","title":"Genetic ancestry contributes to somatic mutations in lung cancers from admixed Latin American populations","description":"Inherited lung cancer risk, particularly in non-smokers, is poorly understood. Genomic and ancestry analysis of 1,153 lung cancers from Latin America revealed striking associations between Native American ancestry and their somatic landscape, including tumor mutational burden (TMB), and specific driver mutations in EGFR, KRAS, and STK11. A local Native American ancestry risk score predicted EGFR and KRAS mutation frequency more strongly than global ancestry, suggesting that germline genetics (rather than environmental exposure) underlie these disparities.","abstract":"Inherited lung cancer risk, particularly in non-smokers, is poorly understood. Genomic and ancestry analysis of 1,153 lung cancers from Latin America revealed striking associations between Native American ancestry and their somatic landscape, including tumor mutational burden (TMB), and specific driver mutations in EGFR, KRAS, and STK11. A local Native American ancestry risk score predicted EGFR and KRAS mutation frequency more strongly than global ancestry, suggesting that germline genetics (rather than environmental exposure) underlie these disparities.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-19T19:13:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004753","title":"Mutation-specific non-canonical pathway of PTEN as a distinct therapeutic target for glioblastoma","description":"PTEN is one of most frequently altered tumor suppressor genes in malignant tumors. The dominant negative effect of PTEN alteration suggests that aberrant function of PTEN mutation might be more disastrous than deletion, the most frequent genomic event in glioblastoma (GBM). This study aimed to understand the functional properties of various PTEN missense mutations and to investigate their clinical relevance. The genomic landscape of PTEN alteration was analyzed using the Samsung Medical Center GBM cohort and validated via The Cancer Genome Atlas dataset. Several hot-spot mutations were identified, and their subcellular distributions and phenotypes were evaluated. We established a library of cancer cell lines that over-express these mutant proteins using the U87MG and patient-derived cell models lacking functional PTEN. PTEN mutations were categorized into two major subsets: missense mutations in the phosphatase domain and truncal mutations in the C2 domain. We determined the subcellular compartmentalization of four mutant proteins (H93Y, C124S, R130Q, and R173C) from the former group and found that they had distinct localizations; those associated with invasive phenotypes (‘edge mutations’) localized to the cell periphery, while the R173C mutant localized to the nucleus. Invasive phenotypes derived from edge substitutions were unaffected by an anti-PI3K/Akt agent but were disrupted by microtubule inhibitors. PTEN mutations exhibit distinct functional properties with regard to their subcellular localization. Further, some missense mutations (‘edge mutations’) in the phosphatase domain caused enhanced invasiveness associated with dysfunctional cytoskeletal assembly, thus suggesting it to be a potent therapeutic target.","abstract":"PTEN is one of most frequently altered tumor suppressor genes in malignant tumors. The dominant negative effect of PTEN alteration suggests that aberrant function of PTEN mutation might be more disastrous than deletion, the most frequent genomic event in glioblastoma (GBM). This study aimed to understand the functional properties of various PTEN missense mutations and to investigate their clinical relevance. The genomic landscape of PTEN alteration was analyzed using the Samsung Medical Center GBM cohort and validated via The Cancer Genome Atlas dataset. Several hot-spot mutations were identified, and their subcellular distributions and phenotypes were evaluated. We established a library of cancer cell lines that over-express these mutant proteins using the U87MG and patient-derived cell models lacking functional PTEN. PTEN mutations were categorized into two major subsets: missense mutations in the phosphatase domain and truncal mutations in the C2 domain. We determined the subcellular compartmentalization of four mutant proteins (H93Y, C124S, R130Q, and R173C) from the former group and found that they had distinct localizations; those associated with invasive phenotypes (‘edge mutations’) localized to the cell periphery, while the R173C mutant localized to the nucleus. Invasive phenotypes derived from edge substitutions were unaffected by an anti-PI3K/Akt agent but were disrupted by microtubule inhibitors. PTEN mutations exhibit distinct functional properties with regard to their subcellular localization. Further, some missense mutations (‘edge mutations’) in the phosphatase domain caused enhanced invasiveness associated with dysfunctional cytoskeletal assembly, thus suggesting it to be a potent therapeutic target.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-20T02:06:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004754","title":"Investigate the evolutionary trajectories during invasiveness acquisition in early lung adenocarcinoma","description":"The evolutionary trajectories of early lung adenocarcinoma (LUAD) have not been fully elucidated. We hypothesize that genomic analysis between pre-invasive and invasive components will facilitate the description of LUAD evolutionary patterns. We micro-dissect malignant pulmonary nodules (MPNs) into paired pre-invasive and invasive components for panel-genomic sequencing and recognize three evolutionary trajectories. Evolutionary mode 1 (EM1) demonstrates none of the common driver events between paired components, but another two modes, EM2A and EM2B, exhibit critical private alterations restricted to pre-invasive and invasive components, respectively. When ancestral clones harbor EGFR mutations, truncal mutation abundance significantly decrease after the acquisition of invasiveness, which may be associated with the intratumoral accumulation of infiltrated B cells. Harboring EGFR mutations is critical to the selective pressure and further impacts the prognosis. Our findings extend the understanding of evolutionary trajectories during invasiveness acquisition in early LUAD.","abstract":"The evolutionary trajectories of early lung adenocarcinoma (LUAD) have not been fully elucidated. We hypothesize that genomic analysis between pre-invasive and invasive components will facilitate the description of LUAD evolutionary patterns. We micro-dissect malignant pulmonary nodules (MPNs) into paired pre-invasive and invasive components for panel-genomic sequencing and recognize three evolutionary trajectories. Evolutionary mode 1 (EM1) demonstrates none of the common driver events between paired components, but another two modes, EM2A and EM2B, exhibit critical private alterations restricted to pre-invasive and invasive components, respectively. When ancestral clones harbor EGFR mutations, truncal mutation abundance significantly decrease after the acquisition of invasiveness, which may be associated with the intratumoral accumulation of infiltrated B cells. Harboring EGFR mutations is critical to the selective pressure and further impacts the prognosis. Our findings extend the understanding of evolutionary trajectories during invasiveness acquisition in early LUAD.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-20T03:20:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004755","title":"Rucaparib in patients presenting a metastatic breast cancer with Homologous Recombination Deficiency, without germline BRCA1/2 mutation, pronostic value of high LOH genomic score and predictive value of HRDetect (microarray)","description":"Breast cancer may present genomic alterations leading to homologous recombination deficiency. PARP inhibitors have proved their efficacy in patients with HER2-negative metastatic breast cancer (mBC) harboring germline (g) BRCA1/2 mutations. We conducted the phase 2 RUBY trial to assess the efficacy of rucaparib in HER2-negative mBC with high genomic loss of heterozygosity (LOH) score or somatic, without gBRCA1/2 mutation. 220 of 711 patients with mBC screened for LOH presented high LOH score which was associated with a higher likelihood of death (HR = 1.39, 95% CI: 1.11-1.75, p = 0.005). The primary objective was not reached with a clinical benefit rate (objective response or SD&gt;16 weeks) of 13.5%. Two LOH-high patients, without somatic BRCA1/2 mutation, presented a complete and durable response (14 and 32 months). HRDetect tended to be associated with response to rucaparib, whithout reaching statistical significance (median HRDetect responders versus non responders: 0.465 versus, 0.040, p = 0.2135). Our data suggests that a small subset of patients with high LOH score could derive benefit from PARP inhibitors.","abstract":"Breast cancer may present genomic alterations leading to homologous recombination deficiency. PARP inhibitors have proved their efficacy in patients with HER2-negative metastatic breast cancer (mBC) harboring germline (g) BRCA1/2 mutations. We conducted the phase 2 RUBY trial to assess the efficacy of rucaparib in HER2-negative mBC with high genomic loss of heterozygosity (LOH) score or somatic, without gBRCA1/2 mutation. 220 of 711 patients with mBC screened for LOH presented high LOH score which was associated with a higher likelihood of death (HR = 1.39, 95% CI: 1.11-1.75, p = 0.005). The primary objective was not reached with a clinical benefit rate (objective response or SD&gt;16 weeks) of 13.5%. Two LOH-high patients, without somatic BRCA1/2 mutation, presented a complete and durable response (14 and 32 months). HRDetect tended to be associated with response to rucaparib, whithout reaching statistical significance (median HRDetect responders versus non responders: 0.465 versus, 0.040, p = 0.2135). Our data suggests that a small subset of patients with high LOH score could derive benefit from PARP inhibitors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-20T09:52:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004756","title":"Rucaparib in patients presenting a metastatic breast cancer with Homologous Recombination Deficiency, without germline BRCA1/2 mutation, pronostic value of high LOH genomic score and predictive value of HRDetect (WGS)","description":null,"abstract":"Breast cancer may present genomic alterations leading to homologous recombination deficiency. PARP inhibitors have proved their efficacy in patients with HER2-negative metastatic breast cancer (mBC) harboring germline (g) BRCA1/2 mutations. We conducted the phase 2 RUBY trial to assess the efficacy of rucaparib in HER2-negative mBC with high genomic loss of heterozygosity (LOH) score or somatic, without gBRCA1/2 mutation. 220 of 711 patients with mBC screened for LOH presented high LOH score which was associated with a higher likelihood of death (HR = 1.39, 95% CI: 1.11-1.75, p = 0.005). The primary objective was not reached with a clinical benefit rate (objective response or SD&gt;16 weeks) of 13.5%. Two LOH-high patients, without somatic BRCA1/2 mutation, presented a complete and durable response (14 and 32 months). HRDetect tended to be associated with response to rucaparib, whithout reaching statistical significance (median HRDetect responders versus non responders: 0.465 versus, 0.040, p = 0.2135). Our data suggests that a small subset of patients with high LOH score could derive benefit from PARP inhibitors.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-20T09:53:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004757","title":"Much ado about nothing? - Off-target amplification can lead to false positive bacterial brain microbiome detection in healthy and Parkinson's disease individuals","description":"Recent studies suggested the existence of (poly-)microbial infections in human brains. Using 16S rRNA gene amplicon sequencing, we tested the hypothesis that there is a bacterial brain microbiome.  We evaluated brain samples from healthy human subjects and individuals suffering from PD (olfactory bulb and pre-frontal cortex). We identified off-target amplification as a major confounding factor in low-bacterial/high-host-DNA scenarios.","abstract":"Recent studies suggested the existence of (poly-)microbial infections in human brains. Using 16S rRNA gene amplicon sequencing, we tested the hypothesis that there is a bacterial brain microbiome.  We evaluated brain samples from healthy human subjects and individuals suffering from PD (olfactory bulb and pre-frontal cortex). We identified off-target amplification as a major confounding factor in low-bacterial/high-host-DNA scenarios.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-20T10:27:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004758","title":"The transition from normal lung anatomy to minimal and established fibrosis in Idiopathic Pulmonary Fibrosis","description":null,"abstract":"Background: The transition from normal lung anatomy to minimal and established fibrosis is a well-established feature of the pathology of idiopathic pulmonary fibrosis (IPF). The purpose of this report is to examine the molecular and cellular mechanisms associated with this transition. \n\nMethods: Pre-operative thoracic MDCT scans of patients with severe IPF (n=9) treated by lung transplantation were used to identify regions of minimal (n=27) and established fibrosis (n=27). Micro-CT, quantitative histology and next-generation sequencing (RNAseq) were used to compare 24 samples from donor controls to minimal and established fibrosis samples. \n\nFindings: The present results confirmed an earlier report showing that the transition from normal lung anatomy to minimal and established fibrosis was associated with a reduction in the numbers of terminal bronchioles. In addition, this study substantially extended those observations by showing the activation of TGFBI, TLRs, NFκB, TGFβ pathways, and T cell co-stimulatory genes, as well as the down-regulation of inhibitory immune checkpoint genes in IPF affected lung tissue. The expression patterns of these genes indicated activation of a field immune response, which is further supported by the increased infiltration of inflammatory immune cells dominated by lymphocytes that are capable of forming the non-encapsulated lymphoid follicles. Fibrosis pathways, mucin secretion, surfactant, and cytokine storm-related genes also participate in the transitions from normal lung anatomy to minimal and established fibrosis.\n\nInterpretation: The transition from normal lung anatomy to minimal and established fibrosis is associated with the up-regulation of TGFBI, TLRs, NFκB, TGFβ pathways, cytokine storm-related genes, and the down-regulation of inhibitory immune checkpoint, surfactant genes as well as the increased infiltration of CD4, CD8, B cell lymphocytes, and macrophages. These molecular and cellular events all contribute to the pathogenesis of IPF.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-21T06:56:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004759","title":"Somatic_mutation_and_clonal_evolution_in_the_human_pancreas_Targeted_Lineage_Bait_Set","description":"Targeted sequencing of humans pancreas samples to understand how embryonic lineages contribute to solid organ development and tissue homeostasis.","abstract":"Targeted sequencing of humans pancreas samples to understand how embryonic lineages contribute to solid organ development and tissue homeostasis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004760","title":"Robust detection of translocations in lymphoma FFPE samples using Targeted Locus Capture-based sequencing","description":"Chromosomal translocations with immunoglobin (IG) loci are the classic drivers in a large subset of B-cell lymphomas. Detection of these translocations is important for confirmation of diagnosis and for prognosis and therapy decisions. Currently, molecular diagnosis of translocations in lymphomas is not addressed well by Next Generation Sequencing (NGS). The standard method for detection of translocations is Fluorescence In Situ Hybridization (FISH), which is labor-intensive, and can be difficult to interpret. There is a need for a robust technology that can be standardized. Targeted Locus Capture (TLC) selectively enriches and sequences entire genes based on the crosslinking of physically proximal sequences, and thereby enables complete sequencing of genes of interest, including detection of large structural variants. Because the technology is based on the crosslinking and fragmenting of DNA, it has particular advantages in the analysis of Formalin-Fixed, Paraffin-Embedded (FFPE) samples, in which DNA is inherently crosslinked and fragmented. In order to validate the FFPE-TLC technology as a novel approach for translocation detection in lymphoma samples, we have developed a panel assay containing genes with frequent translocations (MYC, BCL2, BCL6, IG loci). With this assay we have analyzed &gt;140 lymphoma and control FFPE samples of variable input amounts and qualities that had previously been analyzed with FISH, and a subset also with standard targeted NGS. Good concordance with FISH results was observed for both translocation positive and negative samples. In 10 cases for which FFPE-TLC detected a relevant fusion and FISH had been called negative, discordance could be explained by higher sensitivity of FFPE-TLC or by inconclusive FISH results. In a specific case, FFPE-TLC detected a small-distance rearrangement on chromosome 3 that caused a BCL6 fusion but led to insufficient and therefore undetectable break-apart with FISH. Secondly, the FFPE-TLC approach was tested on a set of 19 B-cell lymphoma FFPE samples that had previously been analyzed using standard targeted NGS and FISH and was enriched for discordant results between these methods. FFPE-TLC-based NGS enables more robust translocation calling as the detection relies on broad sequencing coverage across the translocation partner rather than on breakpoint sequences only. In 3 cases, FFPE-TLC could proof false negative calls in standard targeted NGS due to breakpoints located in regions difficult to capture or to sequence. In 1 case, standard targeted NGS had made a false positive call on a breakpoint sequence that was shown to be caused by a small insertion rather than a genuine translocation. This study shows that FFPE-TLC promises to be a robust alternative for FISH analysis and standard targeted NGS procedures in lymphoma diagnostics and possibly in other cancers with frequent structural variants. The FFPE-TLC approach enables a single, DNA-based NGS test detecting both small mutations and translocations.","abstract":"Chromosomal translocations with immunoglobin (IG) loci are the classic drivers in a large subset of B-cell lymphomas. Detection of these translocations is important for confirmation of diagnosis and for prognosis and therapy decisions. Currently, molecular diagnosis of translocations in lymphomas is not addressed well by Next Generation Sequencing (NGS). The standard method for detection of translocations is Fluorescence In Situ Hybridization (FISH), which is labor-intensive, and can be difficult to interpret. There is a need for a robust technology that can be standardized. Targeted Locus Capture (TLC) selectively enriches and sequences entire genes based on the crosslinking of physically proximal sequences, and thereby enables complete sequencing of genes of interest, including detection of large structural variants. Because the technology is based on the crosslinking and fragmenting of DNA, it has particular advantages in the analysis of Formalin-Fixed, Paraffin-Embedded (FFPE) samples, in which DNA is inherently crosslinked and fragmented. In order to validate the FFPE-TLC technology as a novel approach for translocation detection in lymphoma samples, we have developed a panel assay containing genes with frequent translocations (MYC, BCL2, BCL6, IG loci). With this assay we have analyzed &gt;140 lymphoma and control FFPE samples of variable input amounts and qualities that had previously been analyzed with FISH, and a subset also with standard targeted NGS. Good concordance with FISH results was observed for both translocation positive and negative samples. In 10 cases for which FFPE-TLC detected a relevant fusion and FISH had been called negative, discordance could be explained by higher sensitivity of FFPE-TLC or by inconclusive FISH results. In a specific case, FFPE-TLC detected a small-distance rearrangement on chromosome 3 that caused a BCL6 fusion but led to insufficient and therefore undetectable break-apart with FISH. Secondly, the FFPE-TLC approach was tested on a set of 19 B-cell lymphoma FFPE samples that had previously been analyzed using standard targeted NGS and FISH and was enriched for discordant results between these methods. FFPE-TLC-based NGS enables more robust translocation calling as the detection relies on broad sequencing coverage across the translocation partner rather than on breakpoint sequences only. In 3 cases, FFPE-TLC could proof false negative calls in standard targeted NGS due to breakpoints located in regions difficult to capture or to sequence. In 1 case, standard targeted NGS had made a false positive call on a breakpoint sequence that was shown to be caused by a small insertion rather than a genuine translocation. This study shows that FFPE-TLC promises to be a robust alternative for FISH analysis and standard targeted NGS procedures in lymphoma diagnostics and possibly in other cancers with frequent structural variants. The FFPE-TLC approach enables a single, DNA-based NGS test detecting both small mutations and translocations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-22T09:32:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004761","title":"JAK1_BEDIT_IFNg_screen_1","description":"DNA extraction from cell pellets and plasmid DNA. gRNA library prep using standard gRNA primers.","abstract":"Kozuke pKLV2 standard gRNA PCR procedure. \nFor example, sequence forward before guide: atcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatatatcttgtggaaaggacgaaacacc\nSequence after guide (reverse complement): tgccactttttcaagttgataacggactagccttatttaaacttgctatgctgtttccagcatagctcttaaac","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004762","title":"Reduced_double_gRNA_library_for_scale_limited_CRISPR_Cas9_screens","description":"We have developed a platform for the multiplexed expression of gRNAs and employed it to generate a reduced human genome-wide library that allows to perform large-scale CRISPR/Cas9 screens at a fractionof the cost and labor, compared to conventional libraries. Proof of concept screens were run in K562 cancer cells infected with the reduce, double gRNA library in lentiviral form. Cells were cultured for up to 3 weeks, followed by genomic DNA extraction and targeted amplification of library inserts for sequencing","abstract":"The aim of the current study is to sequence at higher depth samples that have been sequenced at preliminary scale and require ore reads.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004763","title":"Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation","description":"Despite recent advances, the dynamics of genome architecture and chromatin function during human cell differentiation and its potential reorganization upon neoplastic transformation remains poorly characterized. Here, we integrate in situ Hi-C and nine additional omic layers to define and biologically characterize the dynamic changes in three-dimensional (3D) genome architecture across normal B cell differentiation and in neoplastic cells from different subtypes of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) patients. Beyond conventional active (A) and inactive (B) compartments, an integrative analysis of Hi-C data uncovers a highly-dynamic intermediate compartment enriched in poised and polycomb-repressed chromatin. During B cell development, we detect that 28% of the compartments change at defined maturation stages and mostly involve the intermediate compartment. The transition from naive to germinal center B cells is associated with widespread chromatin activation, which mostly reverts into the naive state upon further maturation of germinal center cells into memory B cells. The analysis of CLL and MCL neoplastic cells points both to entity and subtype-specific alterations in chromosome organization. Remarkably, we observe that large chromatin blocks containing key disease-specific genes alter their 3D genome organization. These include the inactivation of a 2Mb region containing the EBF1 gene in CLL and the activation of a 6.1Mb region containing the SOX11 gene in clinically aggressive MCL. This study indicates that 3D genome interactions are extensively modulated during normal B cell differentiation and that the genome of B cell neoplasias acquires a tumor-specific 3D genome architecture.","abstract":"Despite recent advances, the dynamics of genome architecture and chromatin function during human cell differentiation and its potential reorganization upon neoplastic transformation remains poorly characterized. Here, we integrate in situ Hi-C and nine additional omic layers to define and biologically characterize the dynamic changes in three-dimensional (3D) genome architecture across normal B cell differentiation and in neoplastic cells from different subtypes of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) patients. Beyond conventional active (A) and inactive (B) compartments, an integrative analysis of Hi-C data uncovers a highly-dynamic intermediate compartment enriched in poised and polycomb-repressed chromatin. During B cell development, we detect that 28% of the compartments change at defined maturation stages and mostly involve the intermediate compartment. The transition from naive to germinal center B cells is associated with widespread chromatin activation, which mostly reverts into the naive state upon further maturation of germinal center cells into memory B cells. The analysis of CLL and MCL neoplastic cells points both to entity and subtype-specific alterations in chromosome organization. Remarkably, we observe that large chromatin blocks containing key disease-specific genes alter their 3D genome organization. These include the inactivation of a 2Mb region containing the EBF1 gene in CLL and the activation of a 6.1Mb region containing the SOX11 gene in clinically aggressive MCL. This study indicates that 3D genome interactions are extensively modulated during normal B cell differentiation and that the genome of B cell neoplasias acquires a tumor-specific 3D genome architecture.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-22T17:53:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004764","title":"Immunological hallmarks for clinical response to BCG in bladder cancer","description":"Intravesical Bacillus Calmette-Guerin (BCG) is an effective immunotherapy for non-muscle invasive bladder cancer (NMIBC). However, recurrence and progression remain frequent warranting deeper insights into its mechanism. We herein comprehensively profiled blood and tissues obtained from NMIBC patients before, during and after BCG treatment using cytometry by time-of-flight (CyTOF) and RNA sequencing to identify the key immune subsets crucial for anti-tumour activity.","abstract":"Intravesical Bacillus Calmette-Guerin (BCG) is an effective immunotherapy for non-muscle invasive bladder cancer (NMIBC). However, recurrence and progression remain frequent warranting deeper insights into its mechanism. We herein comprehensively profiled blood and tissues obtained from NMIBC patients before, during and after BCG treatment using cytometry by time-of-flight (CyTOF) and RNA sequencing to identify the key immune subsets crucial for anti-tumour activity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-23T07:46:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004765","title":"Metabolic requirements of the metastasis-initiating tumour cell population using oral squamous cell carcinoma (OSCC) as a model system","description":null,"abstract":"Here, we reveal that mitochondrial tRNA methylation is essential for efficient mitochondrial translation to dynamically shape cancer metabolism required for metastasis. Using oral squamous cell carcinoma (OSCC, SCC25 from ATCCR CRL-168TM and patient-derived cell lines with the names VDH01, VDH15) as a model system, we reveal the metabolic requirements of the metastasis-initiating tumour cell population. Only non-dividing tumour cells with high mitochondrial translation rates can invade and disseminate from primary tumours. Thus, inhibition of mitochondrial translation either through deletion of NSUN3 or through pharmacological inhibitors both block metastasis in orthotopic transplantation assays. Together, our study demonstrates that mitochondrial translation controls the metabolic reprogramming required for invasion and dissemination from the primary tumour.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-26T09:18:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004766","title":"Epigenome-wide association study of asthma remission in whole blood and nasal epithelium","description":null,"abstract":"Asthma is a chronic respiratory disease which is not curable, yet some patients experience spontaneous remission.In this study, we hypothesized that epigenetic mechanisms may be involved in asthma remission.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-26T14:42:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004767","title":"Overactivation of the IGF signalling pathway in osteosarcoma","description":"Tumour samples (low coverage WGS) from 35 patients with osteosarcoma were included. All samples were re-evaluated by an experienced bone pathologist who confirmed the diagnosis and a tumour content &gt;50% per sample. All tumours represented conventional high-grade osteosarcomas.","abstract":"Tumour samples (low coverage WGS) from 35 patients with osteosarcoma were included. All samples were re-evaluated by an experienced bone pathologist who confirmed the diagnosis and a tumour content &gt;50% per sample. All tumours represented conventional high-grade osteosarcomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-26T15:17:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004768","title":"RNA-seq of uncultured CD112high and CD112low long-term(LT) human hematopoietic stem cells (HSC) and cultured and lentiviral transduced (CTRL, INKA1-OE) LT- and short-term HSC from umbilical cord blood","description":"We performed RNA-sequencing to elucidate the biological pathways (1) altered by INKA1 overexpression in LT-HSC and ST-HSC that may contribute to the induced transient restraint in generating proliferative hematopoietic output in vivo and in vitro; and (2) that underlie the differential in vitro priming and regeneration phenotypes of CD112high and CD112low LT-HSC. Therefore, we prospectively isolated indicated subpopulations from 3 independent human umbilical cord blood pools and subjected them either to RNA-sequencing directly or following culture, lentiviral transduction and purification of the transduced cell fractions.","abstract":"We performed RNA-sequencing to elucidate the biological pathways (1) altered by INKA1 overexpression in LT-HSC and ST-HSC that may contribute to the induced transient restraint in generating proliferative hematopoietic output in vivo and in vitro; and (2) that underlie the differential in vitro priming and regeneration phenotypes of CD112high and CD112low LT-HSC. Therefore, we prospectively isolated indicated subpopulations from 3 independent human umbilical cord blood pools and subjected them either to RNA-sequencing directly or following culture, lentiviral transduction and purification of the transduced cell fractions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-26T16:19:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004769","title":"Single cell RNA-sequencing (scRNA-seq) of the human hematopoietic stem cell compartment (CD34+CD38-CD45RA-)","description":"To identify a trajectory of human hematopoietic stem cell (HSC) activation single cell gene expression profiling of RNA from human HSC was performed by flow cytometry-based single cell deposition of CD34+CD38—CD45RA—cells from G-CSF-mobilized peripheral blood from 3 individual donors and 1 bone marrow donor in concert with single cell index-sorting (signals indexed: CD34, CD38, CD45RA, CD90, CD49f) and followed by SMARTseq2  based protocol. We show that INKA1 and CDK6/PAK4 expressing single cells segregate across alternative states of quiescence.","abstract":"To identify a trajectory of human hematopoietic stem cell (HSC) activation single cell gene expression profiling of RNA from human HSC was performed by flow cytometry-based single cell deposition of CD34+CD38—CD45RA—cells from G-CSF-mobilized peripheral blood from 3 individual donors and 1 bone marrow donor in concert with single cell index-sorting (signals indexed: CD34, CD38, CD45RA, CD90, CD49f) and followed by SMARTseq2  based protocol. We show that INKA1 and CDK6/PAK4 expressing single cells segregate across alternative states of quiescence.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-26T16:19:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004770","title":"Transcriptomic profiling of prostate cancer metastasis xenograft models reveals conservation of bone microenvironment signatures","description":null,"abstract":"The main objective of the current study is to determine, using transcriptomic analysis on patient derived-xenograft models, whether differentially aggressive PCa tumors predispose their microenvironment (stroma) to a metastatic gene expression pattern. Transcriptomic profiling (RNA Sequencing) was performed on PCa PDX models representing different disease stages; BM18 (androgen dependent bone metastasis) and LAPC9 (androgen independent bone metastasis).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-29T08:28:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004771","title":"Paediatric_CNS_tumour_autopsy_DNA","description":"Investigation of early embryonic mutations can reveal the earliest stages of normal tissue development and the origins of paediatric cancers. Through widespread sampling of tumour, adjacent normal and distant normal samples at autopsy and whole genome sequencing, we aim to establish the point at which lethal paediatic brain tumours diverge from normal development. With many such tumours associated with germline predisposition mutations, we will also be able to investigate the tissue-specific effects these mutations induce.","abstract":"Investigation of early embryonic mutations can reveal the earliest stages of normal tissue development and the origins of paediatric cancers. Through widespread sampling of tumour, adjacent normal and distant normal samples at autopsy and whole genome sequencing, we aim to establish the point at which lethal paediatic brain tumours diverge from normal development. With many such tumours associated with germline predisposition mutations, we will also be able to investigate the tissue-specific effects these mutations induce.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-29T09:26:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004772","title":"Hypertension delays viral clearance and exacerbates airway hyperinflammation in patients with COVID-19","description":"In coronavirus disease 2019 (COVID-19), hypertension and cardiovascular diseases are major risk factors for critical disease progression. However, the underlying causes and the effects of the main anti-hypertensive therapies-angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)-remain unclear. Combining clinical data (n = 144) and single-cell sequencing data of airway samples (n = 48) with in vitro experiments, we observed a distinct inflammatory predisposition of immune cells in patients with hypertension that correlated with critical COVID-19 progression. ACEI treatment was associated with dampened COVID-19-related hyperinflammation and with increased cell intrinsic antiviral responses, whereas ARB treatment related to enhanced epithelial-immune cell interactions. Macrophages and neutrophils of patients with hypertension, in particular under ARB treatment, exhibited higher expression of the pro-inflammatory cytokines CCL3 and CCL4 and the chemokine receptor CCR1. Although the limited size of our cohort does not allow us to establish clinical efficacy, our data suggest that the clinical benefits of ACEI treatment in patients with COVID-19 who have hypertension warrant further investigation.","abstract":"In coronavirus disease 2019 (COVID-19), hypertension and cardiovascular diseases are major risk factors for critical disease progression. However, the underlying causes and the effects of the main anti-hypertensive therapies-angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)-remain unclear. Combining clinical data (n = 144) and single-cell sequencing data of airway samples (n = 48) with in vitro experiments, we observed a distinct inflammatory predisposition of immune cells in patients with hypertension that correlated with critical COVID-19 progression. ACEI treatment was associated with dampened COVID-19-related hyperinflammation and with increased cell intrinsic antiviral responses, whereas ARB treatment related to enhanced epithelial-immune cell interactions. Macrophages and neutrophils of patients with hypertension, in particular under ARB treatment, exhibited higher expression of the pro-inflammatory cytokines CCL3 and CCL4 and the chemokine receptor CCR1. Although the limited size of our cohort does not allow us to establish clinical efficacy, our data suggest that the clinical benefits of ACEI treatment in patients with COVID-19 who have hypertension warrant further investigation.","study_type":"Other","pubmed_ids":[33361824],"external_links":null,"is_released":true,"released_date":"2020-10-29T11:45:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004773","title":"Colorectal cancer cells possess an equipotent capacity to enter a developmental pausing-like state to survive chemotherapy","description":null,"abstract":"Cancer cells enter a reversible drug tolerant persister (DTP) state to evade death from both chemotherapies and targeted agents. It is increasingly appreciated that the DTP state is an important driver of therapy failure and tumor relapse. We combined cellular barcoding and mathematical modeling in patient-derived colorectal cancer xenograft models to identify and characterize the cancer cells capable of generating DTPs in response to standard-of-care chemotherapy. Barcode analysis revealed no loss in clonal complexity of tumors that entered the DTP state and recurred following treatment cessation. Our data fits a mathematical model in which all cancer cells, and not a small subpopulation, possess an equipotent capacity to enter the DTP state. Mechanistically, we determined that DTPs display remarkable transcriptional and functional similarities to diapause, a reversible state of suspended embryonic development triggered by unfavorable environmental conditions. Our study provides new insights into how cancer cells use a developmentally conserved mechanism to drive the DTP state pointing to novel therapeutic opportunities to target diapause-like DTPs.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-10-29T17:41:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004774","title":"Oncolytic virotherapy mediated anti-tumor response: a single-cell perspective","description":null,"abstract":"We analyzed fine-needle aspirate (FNA) samples of T-VEC-treated primary cutaneous B-cell lymphoma patients. FNAs were taken from injected and non-injected lesions before and at several time points after the patient's first injection. The study aimed to describe the dynamics of the viral infection, characterize the changes in the tumor microenvironment caused by T-VEC-treatment compare injected and non-injected lesions and identify the mechanism of action.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004775","title":"ENCORE__New_Targets_for_Effective_Combination_Therapies_in_Tumors_with_Unmet_Medical_Need","description":"This study utilises 2G-CRISPR screens to identify effective target combinations in KRAS-mutant colorectal and triple-negative breast cancer cell lines.","abstract":"Many cancer patients have tumours with resistance to standard of care therapy or have a\nmolecular context that is not addressed by current treatments. Combination therapies aimed at\ninhibiting multiple targets or cancer pathways can combat resistance and exploit new actionable\ndependencies in defined genetic contexts. Critically, the number of possible combinations for\ntarget/pathway inhibition is prohibitively large and we are limited in our ability to predict which\ncombinations of targets are likely to be effective in which patients. We propose to unlock the\npotential of rational target/pathway combinations in oncology through an ambitious integrative\nnetwork biology and functional genomics approach utilising large-scale two-gene combinatorial\nCRISPR (2G-CRISPR) knock-out screens. We will focus on KRAS-mutant colon and triplenegative\nbreast cancers, two cancer types with unmet clinical need with preclinical models\navailable for screening. We aim to identify pathway synergies in these defined genetic contexts\nwhich will be integrated into high density network maps of combination response to inform on\nmechanism. Overall, this project will provide new targets whose inhibition will be effective in\ncombination in the setting of primary or secondary drug resistance.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-01T22:28:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004776","title":"Immunooncology_Cas9_IFNg_screen2","description":"Custom gRNA library previously used by Sarah Consoni. 6 cell pellet samples for DNA extraction and to be sequenced for gRNA","abstract":"One plasmid sample to be sequenced. \nNeed to use custom primers for this as the plasmid is slightly different to Kozuke.\ngLibrary -HiSeq_50bp-SE_U1\tACACTCTTTCCCTACACGACGCTCTTCCGATCTGGCTTTATATATCTTGTGGAAAGGACGAGGTACC\ngLibrary -HiSeq_50bp-SE_L1\nTCGGCATTCCTGCTGAACCGCTCTTCCGATCTccgactcggtgccactttttcaag","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004777","title":"Second hit rare genetic variants in families with seemingly GBA gene associated Parkinson’s disease","description":null,"abstract":"In this study, we explored the possibility that rare variation in the genetic background may be an additional risk factor for Parkinson's Disease (PD) in families segregating pathogenic GBA gene variants. We performed whole-genome sequencing, rare variant filtering, segregation analysis and functional validation of PD cosegregating rare genetic variation in two families segregating PD associated GBA variants c.115+1G&gt;A (ClinVar ID: 93445, ) and p.L444P (ClinVar ID: 4288) respectively. We found rare genetic variation in the HSP70 co-chaperone DnaJ homolog subfamily B member 6 (DNAJB6) and lysosomal protein prosaposin (PSAP) as additional factors possibly influencing PD risk in the two families.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-02T11:54:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004778","title":"Circulating cell-free DNA analyses for Patient Monitoring in Small Cell Lung Cancer","description":null,"abstract":"Introduction\n\nSCLC accounts for approximately 250,000 deaths worldwide each year. Acquisition of adequate tumor biopsy samples is challenging, and liquid biopsies present an alternative option for patient stratification and response monitoring.\nMethods\n\nWe applied whole genome next-generation sequencing to circulating free DNA (cfDNA) from 39 patients with limited-stage (LS) SCLC and 30 patients with extensive-stage SCLC to establish genome-wide copy number aberrations and also performed targeted mutation analysis of 110 SCLC associated genes. Quantitative metrics were calculated for copy number aberrations, including percent genome amplified (PGA [the percentage of genomic regions amplified]), Z-score (a measure of standard deviation), and Moran’s I (a measure of spatial autocorrelation). In addition CellSearch, an epitope-dependent enrichment platform, was used to enumerate circulating tumor cells (CTCs) from a parallel blood sample.\nResults\n\nGenome-wide and targeted cfDNA sequencing data identified tumor-related changes in 94% of patients with LS SCLC and 100% of patients with extensive-stage SCLC. Parallel analysis of CTCs based on at least 1 CTC/7.5 mL of blood increased tumor detection frequencies to 95% for LS SCLC. Both CTC counts and cfDNA readouts correlated with disease stage and overall survival.\nConclusions\n\nWe demonstrate that a simple cfDNA genome-wide copy number approach provides an effective means of monitoring patients through treatment and show that targeted cfDNA sequencing identifies potential therapeutic targets in more than 50% of patients. We are now incorporating this approach into additional studies and trials of targeted therapies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004779","title":"Circulating cell-free DNA analyses for Patient Monitoring in Small Cell Lung Cancer","description":null,"abstract":"Small cell lung cancer (SCLC) accounts for ~250,000 deaths worldwide each year. Acquisition of adequate tumour biopsies is challenging and liquid biopsies present the best option for patient stratification and response monitoring. We present genome-wide and targeted plasma DNA sequencing data that identifies tumour related changes in 91% of limited (LS-SCLC) and 100% of extensive stage (ES-SCLC) patients. Parallel analysis of circulating tumour cells (CTCs, by CellSearch) based on ≥ 1 CTC/7.5ml blood increased tumour detection frequencies to 98% patients (95% for LS-SCLC) where CTC count and plasma DNA readouts correlated with disease stage and overall survival (OS). Targeted plasma DNA sequencing identified potential therapeutic targets in &gt;50% of patients. This approach will support trials of targeted therapies where improved patients outcomes are urgently required.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004780","title":"Cell of Origin and Early Evolution of Leukemia in Down Syndrome","description":null,"abstract":"To investigate the mechanism by which GATA1s and STAG2 deficiency contribute to Down Syndrome leukemogenesis, specifically within the propagating CD34/CD117 cell fractions from primary xenografts, we carried out transcriptional and epigenetic profiling by RNAseq and ATACseq. The chromatin accessibility landscape was compared to bulk ATACseq of\nindividually sorted N-FL HSPC subpopulations.\nTo investigate the mechanism underlying the synergy between T21 and GATA1s in driving preleukemia development, we analyzed the binding occupancy of GATA1. We performed Cut&amp;Run assays to profile\n genome-wide GATA1 binding sites and also to quantify binding changes upon GATA1s editing in N-FL and T21-FL CD34+ enriched HSPCs. Lastly, we profiled miRNAs from N-FL and T21-FL CD34+ enriched\n HSPCs by miRNA-Seq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-02T16:03:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004781","title":"Neuroblastoma tumor heterogeneity and cell plasticity (from PDX and cell lines)","description":"Two cell identities, noradrenergic and mesenchymal, have been characterized in neuroblastoma cell lines according to their epigenetic landscapes relying on specific core regulatory circuitries of transcription factors. Yet, their relationship and relative contribution in patient tumors remain to be defined. Here, we document a spontaneous plasticity between the noradrenergic and mesenchymal identities in a subset of cell lines. Strikingly, mesenchymal neuroblastoma cells revert to a noradrenergic phenotype in vivo. Consistently, tumor cells with a mesenchymal identity are detected in single-cell transcriptomic analyses of neuroblastoma tumors and PDX models. Our data also highlight neuroblastoma intra-tumor heterogeneity with the co-existence of distinct tumor populations, including sympathoblast-like and chromaffin-like cells suggesting that neuroblastoma cells arise from a common sympatho-adrenal progenitor.","abstract":"Two cell identities, noradrenergic and mesenchymal, have been characterized in neuroblastoma cell lines according to their epigenetic landscapes relying on specific core regulatory circuitries of transcription factors. Yet, their relationship and relative contribution in patient tumors remain to be defined. Here, we document a spontaneous plasticity between the noradrenergic and mesenchymal identities in a subset of cell lines. Strikingly, mesenchymal neuroblastoma cells revert to a noradrenergic phenotype in vivo. Consistently, tumor cells with a mesenchymal identity are detected in single-cell transcriptomic analyses of neuroblastoma tumors and PDX models. Our data also highlight neuroblastoma intra-tumor heterogeneity with the co-existence of distinct tumor populations, including sympathoblast-like and chromaffin-like cells suggesting that neuroblastoma cells arise from a common sympatho-adrenal progenitor.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-03T08:37:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004782","title":"Gene expression from human iPSC derived cortical neurons","description":"Gene expression from icas9 human iPSC derived cortical neurons treated with and without doxycycline","abstract":"Gene expression from icas9 human iPSC derived cortical neurons treated with and without doxycycline","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-03T08:49:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004783","title":"Rna-Seq Leiomyosarcoma subtypes","description":"Leiomyosarcomas (LMS) are genetically heterogeneous tumors differentiating along smooth muscle lines. Currently, LMS treatment is not informed by molecular subtyping and is associated with highly variable survival. While disease site continues to dictate clinical management, the contribution of genetic factors to LMS subtype, origins, and timing are unknown. Here we analyzed 70 genomes and 130 transcriptomes of LMS, including multiple tumor regions and paired metastases. Molecular profiling highlighted the extremely early origins of LMS. Three specific subtypes of LMS develop from distinct lineages of smooth muscle cells. Of these, dedifferentiated LMS with high immune infiltration and tumors primarily of gynaecological origin acquired the highest burden of genomic mutation and are associated with worse survival. Homologous recombination defects lead to genome-wide mutational signatures, and a corresponding sensitivity to PARP and other DNA damage response inhibitors, suggesting a novel  therapeutic    strategy for LMS. Finally, by phylogenetic reconstruction, we present evidence that clones seeding lethal metastases arise decades prior to LMS diagnosis.","abstract":"Leiomyosarcomas (LMS) are genetically heterogeneous tumors differentiating along smooth muscle lines. Currently, LMS treatment is not informed by molecular subtyping and is associated with highly variable survival. While disease site continues to dictate clinical management, the contribution of genetic factors to LMS subtype, origins, and timing are unknown. Here we analyzed 70 genomes and 130 transcriptomes of LMS, including multiple tumor regions and paired metastases. Molecular profiling highlighted the extremely early origins of LMS. Three specific subtypes of LMS develop from distinct lineages of smooth muscle cells. Of these, dedifferentiated LMS with high immune infiltration and tumors primarily of gynaecological origin acquired the highest burden of genomic mutation and are associated with worse survival. Homologous recombination defects lead to genome-wide mutational signatures, and a corresponding sensitivity to PARP and other DNA damage response inhibitors, suggesting a novel  therapeutic    strategy for LMS. Finally, by phylogenetic reconstruction, we present evidence that clones seeding lethal metastases arise decades prior to LMS diagnosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-04T05:47:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004784","title":"Mechanisms of active DNA demethylation in human monocytes","description":null,"abstract":"The differentiation of human blood monocytes (MO), the post-mitotic precursors of macrophages (MAC) and dendritic cells (moDC), is accompanied by the active turnover of DNA methylation, but the extent, consequences and mechanisms of DNA methylation changes remain unclear. Here we profile and compare epigenetic landscapes during IL-4/GM-CSF-driven MO differentiation across the genome and detect several thousand regions that are actively demethylated during culture, both with or without accompanying changes in chromatin accessibility or transcription factor (TF) binding. We further identify TF that are globally associated with DNA demethylation processes. While interferon regulatory factor 4 (IRF4) is found to control hallmark DC functions with less impact on DNA methylation, early growth response 2 (EGR2), proves essential for MO differentiation as well as DNA methylation turnover at its binding sites. EGR2 is shown to interact with the 5mC hydroxylase TET2 and its consensus sequences show a characteristic DNA methylation footprint at demethylated sites with or without detectable protein binding. Our findings reveal a novel and essential role for EGR2 as epigenetic pioneer in human MO and suggest that active DNA demethylation can be initiated by TET2 recruiting TF both at stable and transient binding sites.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-04T10:10:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004785","title":"Whole-genome samples from 12 subjects of Family 2; a family with a high prevalence of psychosis","description":null,"abstract":"We investigated the genetic causes of major mental disorders (MMDs) including schizophrenia, bipolar disorder I, major depressive disorder, and attention deficit hyperactive disorder, in a large family pedigree from Alpujarras, South of Spain, a region with a high prevalence of psychotic disorders. We applied a systematic genomic approach based on karyotyping (N=4), genotyping by genome-wide SNP array (N=33), whole-exome sequencing (N=4), and whole-genome sequencing (N=12). We performed genome-wide linkage analysis, family-based association analysis, and polygenic risk score estimates. Significant linkage was obtained at chromosome 9 (9q33.1-33.2, LOD score= 4.11), a suggestive region that contains five candidate genes ASTN2, BRINP1, C5, TLR4, and TRIM32, previously associated to MMDs. Comprehensive analysis associated the MMD phenotype with genes of the immune system with dual brain functions. Moreover, the psychotic phenotype was enriched for genes involved in synapsis. These results should be considered once studying the genetics of psychiatric disorders in other families, especially the ones from the same region, since founder effects may be related to the high prevalence.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004786","title":"Genomics-based personalized oncology in cancer of unknown primary (CUP, project H021)","description":"To perform a comprehensive genomic characterization of 70 patients suffering from cancer of unknown primary (CUP) we used whole-exome, whole-genome, transcriptome and methylome analysis. We detected a substantial mutational heterogeneity with genes most commonly affected by SNVs, indels and fusions being TP53, TTN, MUC16, ABCA13, COL6A3, KRAS, LRP1B, XIRP2 and CSMD3. The most common fusion involved FGFR2, the most common focal deletion affected CDKN2A. A molecular tumor board recommended genomics-based therapies in 56/70 (80%) patients which were applied in 20/56 (35.7%) cases. Entity predictions based on transcriptome and methylome data could be made in up to 62/70 (88.6%) cases but were conclusive in only 16/48 (33.3%) cases. Germline analysis revealed 6 (likely) pathogenic mutations in 5 patients. Recommended therapies translated into a mean PFS2/1 ratio of 3.61 (median=2.25) with a median PFS1 of 89 days (n=17) compared to a median PFS2 of 182.5 days (n=20). Our data emphasize the clinical benefit of comprehensive genetic approaches in diagnostic and therapeutic management and underline the need for innovative, mechanism-based clinical trials in this heterogeneous group of diseases.","abstract":"To perform a comprehensive genomic characterization of 70 patients suffering from cancer of unknown primary (CUP) we used whole-exome, whole-genome, transcriptome and methylome analysis. We detected a substantial mutational heterogeneity with genes most commonly affected by SNVs, indels and fusions being TP53, TTN, MUC16, ABCA13, COL6A3, KRAS, LRP1B, XIRP2 and CSMD3. The most common fusion involved FGFR2, the most common focal deletion affected CDKN2A. A molecular tumor board recommended genomics-based therapies in 56/70 (80%) patients which were applied in 20/56 (35.7%) cases. Entity predictions based on transcriptome and methylome data could be made in up to 62/70 (88.6%) cases but were conclusive in only 16/48 (33.3%) cases. Germline analysis revealed 6 (likely) pathogenic mutations in 5 patients. Recommended therapies translated into a mean PFS2/1 ratio of 3.61 (median=2.25) with a median PFS1 of 89 days (n=17) compared to a median PFS2 of 182.5 days (n=20). Our data emphasize the clinical benefit of comprehensive genetic approaches in diagnostic and therapeutic management and underline the need for innovative, mechanism-based clinical trials in this heterogeneous group of diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-06T13:32:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004787","title":"Familial psychosis associated with a missense mutation at MACF1 gene combined with the rare duplications DUP3p26.3 and DUP16p23.3, affecting the CNTN6 and CDH13 genes","description":null,"abstract":"Psychosis is a highly heritable and heterogeneous psychiatric condition. Its genetic architecture is thought to be the result of the joint effect of common and rare variants. Families with high prevalence are an interesting approach to shed light on the rare variant's contribution without the need of collecting large cohorts. To unravel the genomic architecture of a family enriched for psychosis, with four affected individuals, we applied a system genomic approach based on karyotyping, genotyping by whole-exome sequencing to search for rare single nucleotide polymorphisms (SNPs) and SNP array to search for copy-number variants (CNVs). We identified a rare non-synonymous variant, g.39914279 C&gt;G, in the MACF1 gene, segregating with psychosis. Rare variants in the MACF1 gene have been previously detected in SCZ patients. Besides, two rare CNVs, DUP3p26.3 and DUP16p23.3, were also identified in the family affecting relevant genes (CNTN6 and CDH13, respectively). We hypothesize that the co-segregation of these duplications with the rare variant g.39914279 C&gt;G of MACF1 gene precipitated with schizophrenia and schizoaffective disorder.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004788","title":"Methylation analysis for plasma DNA of patients with organ transplantation","description":"We developed Genetic-Epigenetic Tissue Mapping (GETMap) to determine the tissue composition of plasma DNA carrying genetic variants not present in the constitutional genome through comparing their methylation profiles with relevant tissues. We validated this approach by showing that, in pregnant women, circulating DNA carrying fetal-specific alleles was entirely placenta-derived.","abstract":"We developed Genetic-Epigenetic Tissue Mapping (GETMap) to determine the tissue composition of plasma DNA carrying genetic variants not present in the constitutional genome through comparing their methylation profiles with relevant tissues. We validated this approach by showing that, in pregnant women, circulating DNA carrying fetal-specific alleles was entirely placenta-derived.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-09T07:28:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004789","title":"MutationalPatterns2: The one stop shop for the analysis of mutational processes: DNA repair deletions","description":null,"abstract":"We developed MutationalPatterns2, a package for the analysis of mutational processes. To show how the package can be used to generate novel biological insights, we applied it on genome mutation data of cell lines in which we deleted specific DNA repair processes. We generated HPRT-only knockout lines as well as the combination of HPRT with MSH2, UNG and XPC. Whole genome sequencing was performed on generated clones and subclones. By subtracting variants present in the clones from those in the subclones, the somatic mutations, that accumulated in between the clonal steps, were determined.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-09T09:09:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004790","title":"HCA_Muscle_Adult_WSSS_RNA","description":"Molecuar regulation of human skeletal muscle development and maintainance.\n\nThe goal of this study is to understand the molecuar regulation of human skeletal muscle development and maintainance. Single cells and single nuclei are isolated from human skeletal muscles and purified with percoll gradient centrifugation. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Molecuar regulation of human skeletal muscle development and maintainance.\n\nThe goal of this study is to understand the molecuar regulation of human skeletal muscle development and maintainance. Single cells and single nuclei are isolated from human skeletal muscles and purified with percoll gradient centrifugation. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004791","title":"Familial psychosis associated with a missense mutation at MACF1 gene combined with the rare duplications DUP3p26.3 and DUP16p23.3, affecting the CNTN6 and CDH13 genes","description":"Psychosis is a highly heritable and heterogeneous psychiatric condition. Its genetic architecture is thought to be the result of the joint effect of common and rare variants. Families with high prevalence are an interesting approach to shed light on the rare variant's contribution without the need of collecting large cohorts. To unravel the genomic architecture of a family enriched for psychosis, with four affected individuals, we applied a system genomic approach based on karyotyping, genotyping by whole-exome sequencing to search for rare single nucleotide polymorphisms (SNPs) and SNP array to search for copy-number variants (CNVs). We identified a rare non-synonymous variant, g.39914279 C&amp;gt;G, in the MACF1 gene, segregating with psychosis. Rare variants in the MACF1 gene have been previously detected in SCZ patients. Besides, two rare CNVs, DUP3p26.3 and DUP16p23.3, were also identified in the family affecting relevant genes (CNTN6 and CDH13, respectively). We hypothesize that the co-segregation of these duplications with the rare variant g.39914279 C&amp;gt;G of MACF1 gene precipitated with schizophrenia and schizoaffective disorder.","abstract":"Psychosis is a highly heritable and heterogeneous psychiatric condition. Its genetic architecture is thought to be the result of the joint effect of common and rare variants. Families with high prevalence are an interesting approach to shed light on the rare variant's contribution without the need of collecting large cohorts. To unravel the genomic architecture of a family enriched for psychosis, with four affected individuals, we applied a system genomic approach based on karyotyping, genotyping by whole-exome sequencing to search for rare single nucleotide polymorphisms (SNPs) and SNP array to search for copy-number variants (CNVs). We identified a rare non-synonymous variant, g.39914279 C&amp;gt;G, in the MACF1 gene, segregating with psychosis. Rare variants in the MACF1 gene have been previously detected in SCZ patients. Besides, two rare CNVs, DUP3p26.3 and DUP16p23.3, were also identified in the family affecting relevant genes (CNTN6 and CDH13, respectively). We hypothesize that the co-segregation of these duplications with the rare variant g.39914279 C&amp;gt;G of MACF1 gene precipitated with schizophrenia and schizoaffective disorder.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-11T18:28:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004792","title":"RNA-seq study of a Princess Margaret Cancer Centre human acute myeloid leukemia patient cohort","description":"The PMCC AML RNAseq dataset consists of 81 AML patient samples (clinical data in Supplemental Table 11 of manuscript),  processed in two batches. These patient samples are able to engraft in the NSG (NOD.Cg PrkdcscidIl2rgtm1Wjl /SzJ) mouse model. Five patients (90543, 598, 90240, 110484, 100500) were included in both batches. Viaably frozen material from the Leukemia Tissue Bank at Princess Margaret Cancer Centre/ University Health Network were thawed by dropwise addition of X-VIVO + 50% fetal calf serum supplemented with DNase (100μg/mL final concentration, Roche). RNA was extracted from bulk peripheral blood mononuclear cells (PBMC) using the RNeasy Micro Kit (Qiagen Inc.). A paired-end 76 base-pair flow-cell lane Illumina High seq 2000 yielded an average of 240 million sequence reads aligning to genome per sample at the Genome Sciences Centre, BC Cancer Agency for cohort 1. Cohort 2 was subjected to 125 bp, paired-end RNA-sequencing on the Illumina HiSeq 2500 with an average of 50 million reads/sample at the Centre for Applied Genomics, Sick Kids Hospital.","abstract":"The PMCC AML RNAseq dataset consists of 81 AML patient samples (clinical data in Supplemental Table 11 of manuscript),  processed in two batches. These patient samples are able to engraft in the NSG (NOD.Cg PrkdcscidIl2rgtm1Wjl /SzJ) mouse model. Five patients (90543, 598, 90240, 110484, 100500) were included in both batches. Viaably frozen material from the Leukemia Tissue Bank at Princess Margaret Cancer Centre/ University Health Network were thawed by dropwise addition of X-VIVO + 50% fetal calf serum supplemented with DNase (100μg/mL final concentration, Roche). RNA was extracted from bulk peripheral blood mononuclear cells (PBMC) using the RNeasy Micro Kit (Qiagen Inc.). A paired-end 76 base-pair flow-cell lane Illumina High seq 2000 yielded an average of 240 million sequence reads aligning to genome per sample at the Genome Sciences Centre, BC Cancer Agency for cohort 1. Cohort 2 was subjected to 125 bp, paired-end RNA-sequencing on the Illumina HiSeq 2500 with an average of 50 million reads/sample at the Centre for Applied Genomics, Sick Kids Hospital.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-11T18:53:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004793","title":"Compound heterozygous variants in LAMC3 in association with posterior periventricular nodular heterotopia","description":"Periventricular nodular heterotopia is a malformation of cortical development characterized by nodules of abnormally migrated neurons.","abstract":"Periventricular nodular heterotopia is a malformation of cortical development characterized by nodules of abnormally migrated neurons.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-12T05:37:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004794","title":"RNAseq cutaneous and uveal melanoma liver metastases","description":"RNA sequencing analyses of tumor liver metastases from untreated cutaneous melanoma (CM) and uveal melanoma (UM) patients.","abstract":"RNA sequencing analyses of tumor liver metastases from untreated cutaneous melanoma (CM) and uveal melanoma (UM) patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-12T07:37:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004795","title":"WES cutaneous and uveal melanoma liver metastases","description":"Whole exome sequencing analyses of tumor liver metastases from untreated cutaneous melanoma (CM) and uveal melanoma (UM) patients.","abstract":"Whole exome sequencing analyses of tumor liver metastases from untreated cutaneous melanoma (CM) and uveal melanoma (UM) patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-12T07:37:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004796","title":"Neuroblastoma Cell Line Circle-seq","description":"We generated Circle-seq data for 12 neuroblastoma cell lines to describe the landscape of extrachromosomal circular DNA in neuroblastoma.","abstract":"We generated Circle-seq data for 12 neuroblastoma cell lines to describe the landscape of extrachromosomal circular DNA in neuroblastoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-12T11:48:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004797","title":"Primary Neuroblastoma Circle-seq","description":"We generated Circle-seq data for primary neuroblastoma to describe the landscape of extrachromosomal circular DNA in neuroblastoma.","abstract":"We generated Circle-seq data for primary neuroblastoma to describe the landscape of extrachromosomal circular DNA in neuroblastoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-12T12:04:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004798","title":"RNA-seq study of  human long-term and short-term hematopoietic stem cells from umblical cord blood with lentiviral overexpression of S1PR3","description":"To investigate the molecular and biological pathways altered by S1PR3OE in human hematopoietic stem cells (HSC), we performed RNA-sequencing (RNA-seq) of LT- and ST-HSC 3 days after transduction with control or S1PR3 overexpression (OE) lentiviral vectors.  LT-HSC and ST-HSC from 3 pool of CB lin- were FACS-purified, cells were prestimulated for 4 hours and transduced with lentiviral vectors. At day 3, 2000-5300 BFP+ cells were FACS-purified for RNA isolation with a PicoPure kit.  We were able to isolate only 1600-1800 BFP+ cells from LT-HSC control samples as opposed to 4000-5400 BFP+ cells from S1PR3OE samples. Thus, we pooled all control BFP+ LT-HSC cells into one sample for RNA-seq analysis. BFP- LT-HSC from control vector transduction were purified from CB1 as an additional LT-HSC control. Nextera libraries generated from 10 ng RNA from 5 LT-HSC samples (2 controls, 3 S1PR3OE) and 6 ST-HSC samples (3 controls, 3 S1PR3OE) were subjected to 125 bp, paired-end RNA-sequencing on the Illumina HiSeq 2500 with an average of 50 million reads/sample at the Center for Applied Genomics, Sick Kids Hospital.","abstract":"To investigate the molecular and biological pathways altered by S1PR3OE in human hematopoietic stem cells (HSC), we performed RNA-sequencing (RNA-seq) of LT- and ST-HSC 3 days after transduction with control or S1PR3 overexpression (OE) lentiviral vectors.  LT-HSC and ST-HSC from 3 pool of CB lin- were FACS-purified, cells were prestimulated for 4 hours and transduced with lentiviral vectors. At day 3, 2000-5300 BFP+ cells were FACS-purified for RNA isolation with a PicoPure kit.  We were able to isolate only 1600-1800 BFP+ cells from LT-HSC control samples as opposed to 4000-5400 BFP+ cells from S1PR3OE samples. Thus, we pooled all control BFP+ LT-HSC cells into one sample for RNA-seq analysis. BFP- LT-HSC from control vector transduction were purified from CB1 as an additional LT-HSC control. Nextera libraries generated from 10 ng RNA from 5 LT-HSC samples (2 controls, 3 S1PR3OE) and 6 ST-HSC samples (3 controls, 3 S1PR3OE) were subjected to 125 bp, paired-end RNA-sequencing on the Illumina HiSeq 2500 with an average of 50 million reads/sample at the Center for Applied Genomics, Sick Kids Hospital.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-12T18:10:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004799","title":"The CCGA study is a large, prospective, observational, multi-center study with longitudinal follow-up. This subset of samples is from the first of three sub-studies.","description":"The CCGA study is designed to develop and validate a multi-cancer early detection test. Samples from this first sub-study were used in the development phase, where prototype sequencing assays and classifiers were utilized to identify the highest-performing assay with this to move forward into development. This is a subset of 1,400 samples analyzed with whole-genome sequencing.","abstract":"The CCGA study is designed to develop and validate a multi-cancer early detection test. Samples from this first sub-study were used in the development phase, where prototype sequencing assays and classifiers were utilized to identify the highest-performing assay with this to move forward into development. This is a subset of 1,400 samples analyzed with whole-genome sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004800","title":"BRCA2, ATM, and CDK12 defects differentially shape prostate tumor driver genomics and clinical aggression","description":null,"abstract":"DNA damage repair (DDR) defects are common across cancer types and indicate vulnerability to targeted therapies. In prostate cancer there is an urgent need for practical DDR defect detection strategies and resolution of associated clinicogenomic features. Here, we profiled circulating tumor DNA (ctDNA) from metastatic prostate cancer patients and identified BRCA2, ATM, and CDK12 as the most frequently disrupted DDR genes. CtDNA analysis distinguished monoallelic from biallelic defects and revealed mechanistic heterogeneity underlying biallelic inactivation. BRCA2-deficient samples exhibited frequent disruption of tumor suppressors via chromosomal rearrangements, while CDK12 mutations were instead associated with oncogene amplification. ATM-mutation appeared mutually exclusive with TP53 mutation. Loss of BRCA2 and CDK12—but not ATM—was associated with inferior clinical outcomes compared to DDR-intact disease. Our results suggest that distinct DDR aberrations differentially shape tumor genomics and clinical aggression. The ease of DDR-defect characterization in ctDNA suggests that blood-based assays can help identify patients suitable for exploitative therapies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-13T00:12:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004801","title":"testest","description":null,"abstract":"ok","study_type":"Synthetic Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004802","title":"testtest","description":null,"abstract":"testestestestes","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004803","title":"RNA-seq study of a Princess Margaret Cancer Centre human acute myeloid leukemia patient cohort","description":null,"abstract":"The PMCC AML RNAseq dataset consists of 81 AML patient samples (clinical data in Supplemental Table 11 of manuscript),  processed in two batches. These patient samples are able to engraft in the NSG (NOD.Cg PrkdcscidIl2rgtm1Wjl /SzJ) mouse model. Five patients (90543, 598, 90240, 110484, 100500) were included in both batches. Viaably frozen material from the Leukemia Tissue Bank at Princess Margaret Cancer Centre/ University Health Network were thawed by dropwise addition of X-VIVO + 50% fetal calf serum supplemented with DNase (100μg/mL final concentration, Roche). RNA was extracted from bulk peripheral blood mononuclear cells (PBMC) using the RNeasy Micro Kit (Qiagen Inc.). A paired-end 76 base-pair flow-cell lane Illumina High seq 2000 yielded an average of 240 million sequence reads aligning to genome per sample at the Genome Sciences Centre, BC Cancer Agency for cohort 1. Cohort 2 was subjected to 125 bp, paired-end RNA-sequencing on the Illumina HiSeq 2500 with an average of 50 million reads/sample at the Centre for Applied Genomics, Sick Kids Hospital.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004804","title":"RNA-seq study of  human long-term and short-term hematopoietic stem cells from umblical cord blood with lentiviral overexpression of S1PR3","description":null,"abstract":"To investigate the molecular and biological pathways altered by S1PR3OE in human hematopoietic stem cells (HSC), we performed RNA-sequencing (RNA-seq) of LT- and ST-HSC 3 days after transduction with control or S1PR3 overexpression (OE) lentiviral vectors.  LT-HSC and ST-HSC from 3 pool of CB lin- were FACS-purified, cells were prestimulated for 4 hours and transduced with lentiviral vectors. At day 3, 2000-5300 BFP+ cells were FACS-purified for RNA isolation with a PicoPure kit.  We were able to isolate only 1600-1800 BFP+ cells from LT-HSC control samples as opposed to 4000-5400 BFP+ cells from S1PR3OE samples. Thus, we pooled all control BFP+ LT-HSC cells into one sample for RNA-seq analysis. BFP- LT-HSC from control vector transduction were purified from CB1 as an additional LT-HSC control. Nextera libraries generated from 10 ng RNA from 5 LT-HSC samples (2 controls, 3 S1PR3OE) and 6 ST-HSC samples (3 controls, 3 S1PR3OE) were subjected to 125 bp, paired-end RNA-sequencing on the Illumina HiSeq 2500 with an average of 50 million reads/sample at the Center for Applied Genomics, Sick Kids Hospital.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004805","title":"Single cell RNA sequencing of relapsed/refractory multiple myeloma","description":null,"abstract":"Most multiple myeloma patients develop refractory disease over time but the high tumor heterogeneity and complex interactions with the microenvironment make decisions on treatment challenging. Here, we have analyzed bone marrow aspirates of 20 relapsed/refractory multiple myeloma (RRMM) patients by single cell RNA-sequencing. We identify a transcriptional signature of the high-risk chromosome 1q gain and associated subclone dynamics over treatment. In the immune cell compartment, we observe an accumulation of exhausted gamma/delta T-cells and myeloid cells with immunosuppressive features. Via a co-expression analysis of receptor-ligand pairs we find that the underlying mechanisms include an upregulation of inflammatory cytokines and ligands of inhibitory receptors expressed on T and NK-cells. Finally, we identify microenvironmental changes that are specific for patients with 1q gain. Thus, our study resolves transcriptonal features of subclones in RRMM and mechanisms of microenvironmental reprogramming that can guide clinical decision making. Four WGS samples from hipo-K08K and hipo-067 were used as control.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-13T16:51:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004806","title":"NovaSeq","description":null,"abstract":"Ultra Low-Passage Whole Genome Sequencing for RRD cancers to use as a germline diagnostic tool.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004807","title":"Whole Genome Sequencing Data of Replication Repair Deficient Cancers","description":null,"abstract":"The hallmark of mismatch repair deficient cancers is microsatellite instability, and it is used to diagnose germline mismatch repair deficiency. The only other active DNA replication repair mechanism is the polymerase’s intrinsic proofreading domain, which is thought to solely repair mismatches, and not microsatellite frameshift mutations created by the slippage of the polymerase itself. We highlight different frameshift mutation signatures created by mismatch repair and polymerase proofreading deficiencies, the non-stochastic nature of unique frameshifts that are size-dependent and target a fixed microsatellite length, and the use of these mutations to diagnose mismatch repair deficiency and predict immunotherapy response in mismatch repair deficient cancers. This report uncovers novel biological aspects of microsatellite instability, as well as its application to improve the diagnosis and treatment of mismatch repair deficient cancers.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004808","title":"CTCF-dependent enhancer hijacking by the EVI1 oncogene in leukemia","description":"Chromosomal rearrangements are a frequent cause of oncogene deregulation in human malignancies. Overexpression of EVI1 is found in a subgroup of acute myeloid leukemia (AML) with 3q26 chromosomal rearrangements which are often therapy resistant. In a cohort of primary t(3;8)(q26;q24) AML samples we observed the translocation of a MYC super-enhancer to EVI1. We generated a patient-based t(3;8)(q26;q24) model in vitro using CRISPR-Cas9 technology and demonstrated hyper-activation of EVI1 by the hijacked MYC super-enhancer. One MYC super-enhancer element in particular, which recruits early hematopoietic regulators, is critical for EVI1 expression and enhancer-promoter interaction. This interaction is facilitated by a CTCF-bound motif upstream of the EVI1 promoter that acts as an enhancer-docking site in t(3;8) AML. Genomic analyses of 3q26-rearranged AML samples point to a common mechanism by which EVI1 uses this CTCF-bound enhancer-docking site to hijack early hematopoietic enhancers.","abstract":"Chromosomal rearrangements are a frequent cause of oncogene deregulation in human malignancies. Overexpression of EVI1 is found in a subgroup of acute myeloid leukemia (AML) with 3q26 chromosomal rearrangements which are often therapy resistant. In a cohort of primary t(3;8)(q26;q24) AML samples we observed the translocation of a MYC super-enhancer to EVI1. We generated a patient-based t(3;8)(q26;q24) model in vitro using CRISPR-Cas9 technology and demonstrated hyper-activation of EVI1 by the hijacked MYC super-enhancer. One MYC super-enhancer element in particular, which recruits early hematopoietic regulators, is critical for EVI1 expression and enhancer-promoter interaction. This interaction is facilitated by a CTCF-bound motif upstream of the EVI1 promoter that acts as an enhancer-docking site in t(3;8) AML. Genomic analyses of 3q26-rearranged AML samples point to a common mechanism by which EVI1 uses this CTCF-bound enhancer-docking site to hijack early hematopoietic enhancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-13T22:59:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004809","title":"BIOKEY: A single-cell catalogue of the dynamic changes underlying Checkpoint Immunotherapy response in Early Breast Cancer","description":"Checkpoint immunotherapy combined with neoadjuvant chemotherapy improves complete pathologic response in a subset of breast cancer patients. Here, we applied single-cell profiling to tumor biopsies collected before and during anti-PD1 therapy. One-third of tumors exhibited proliferative T-cells expanding along CD8+ or CD4+ lineages, which were either characterized by increased cytotoxicity and exhaustion or improved T-helper function, respectively. Lineage tracing in non-expanding tumors revealed at which point in the lineage T-cells were impaired, while gene expression modeling along these lineages revealed novel genes and underlying transcription factors involved in T-cell expansion. Interestingly, different dendritic and myeloid cell phenotypes could either stimulate or inhibit expanding T-cells, while cell-to-cell communication revealed an integrated immune context highly predictive of T-cell expansion, consisting of immune-stimulatory/-inhibitory interactions between cancer and various immune cell types. Our data yield unprecedented insights into the dynamic changes underlying checkpoint immunotherapy response in breast cancer.","abstract":"Checkpoint immunotherapy combined with neoadjuvant chemotherapy improves complete pathologic response in a subset of breast cancer patients. Here, we applied single-cell profiling to tumor biopsies collected before and during anti-PD1 therapy. One-third of tumors exhibited proliferative T-cells expanding along CD8+ or CD4+ lineages, which were either characterized by increased cytotoxicity and exhaustion or improved T-helper function, respectively. Lineage tracing in non-expanding tumors revealed at which point in the lineage T-cells were impaired, while gene expression modeling along these lineages revealed novel genes and underlying transcription factors involved in T-cell expansion. Interestingly, different dendritic and myeloid cell phenotypes could either stimulate or inhibit expanding T-cells, while cell-to-cell communication revealed an integrated immune context highly predictive of T-cell expansion, consisting of immune-stimulatory/-inhibitory interactions between cancer and various immune cell types. Our data yield unprecedented insights into the dynamic changes underlying checkpoint immunotherapy response in breast cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-15T19:50:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004810","title":"BCL11B enhancer hijacking defines a subtype of lineage ambiguous stem cell leukemia","description":"Hijacking of primitive hematopoietic enhancers, or generation of a neo-enhancer by genomic amplification, results in deregulation of BCL11B as the defining feature of a subset of T/myeloid leukemia","abstract":"Hijacking of primitive hematopoietic enhancers, or generation of a neo-enhancer by genomic amplification, results in deregulation of BCL11B as the defining feature of a subset of T/myeloid leukemia","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-15T21:19:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004812","title":"Integrative multi-omic analyses of malignant pleural mesothelioma","description":"Multi-omic data (whole-genome sequencing, RNA-seq, EPIC 850K methylation arrays) for 123 samples from the MESOMICS project, the French project of molecular characterization of malignant pleural mesothelioma","abstract":"Multi-omic data (whole-genome sequencing, RNA-seq, EPIC 850K methylation arrays) for 123 samples from the MESOMICS project, the French project of molecular characterization of malignant pleural mesothelioma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-16T09:57:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004813","title":"Comprehensive Genomic and Transcriptomic Analysis of Rare Cancers for Guiding of Therapy (H021)","description":"Here we analyzed the molecular profiles and clinical outcomes of 1,310 patients (proportion of rare cancers, 75%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults with incurable cancers. Based on 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment, in 88% of cases. Recommended therapies were administered in 362 of 1,138 patients (31.8%) and resulted in significantly improved response and disease control rates (23.9% and 55.3%, respectively) compared to previous therapies, translating into a progression-free survival ratio &gt;1.3 in 35.7% of patients.","abstract":"Here we analyzed the molecular profiles and clinical outcomes of 1,310 patients (proportion of rare cancers, 75%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults with incurable cancers. Based on 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment, in 88% of cases. Recommended therapies were administered in 362 of 1,138 patients (31.8%) and resulted in significantly improved response and disease control rates (23.9% and 55.3%, respectively) compared to previous therapies, translating into a progression-free survival ratio &gt;1.3 in 35.7% of patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-16T11:14:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004814","title":"Transcriptional profiling of ovarian tumours and cell lines","description":"Purpose: Endogenous retroviruses (ERVs) play a role in a variety of biological processes, including embryogenesis and cancer. DNA methyltransferase inhibitors (DNMTi)-induced ERV expression triggers interferon responses in ovarian cancer cells via the viral sensing machinery. Baseline expression of ERVs also occurs in cancer cells, though this process is poorly understood and previously unexplored in epithelial ovarian cancer (EOC).\nHere, the prognostic and immunomodulatory consequences of baseline ERV expression was assessed in EOC.\nExperimental Design: ERV expression was assessed using EOC transcriptional data from TCGA and from an independent cohort (HH), as well as from untreated or DNMTi-treated EOC cell lines. LASSO logistic regression defined an ERV expression score to predict patient prognosis. Immunohistochemistry (IHC) was conducted on the HH cohort. Combination of DNMTi treatment with γδ T cells was tested in vitro, using EOC cell lines and patient-derived tumor cells.\nResults: ERV expression was found to define clinically relevant subsets of EOC patients. An ERV prognostic score was successfully generated in TCGA and validated in the independent cohort. In EOC patients from this cohort, a high ERV score was associated with better survival (log-rank p=0.0009) and correlated with infiltration of CD8+PD1+ T cells (r=0.46, p=0.0001).\nIn vitro, baseline ERV expression dictates the level of ERV induction in response to DNMTi. Manipulation of ERV expression by DNMTi resulted in improved EOC cell killing by cytotoxic immune cells.\nConclusions: These findings uncover the potential for baseline ERV expression to robustly inform EOC patient prognosis, influence tumor immune infiltration and affect anti-tumor immunity.","abstract":"Purpose: Endogenous retroviruses (ERVs) play a role in a variety of biological processes, including embryogenesis and cancer. DNA methyltransferase inhibitors (DNMTi)-induced ERV expression triggers interferon responses in ovarian cancer cells via the viral sensing machinery. Baseline expression of ERVs also occurs in cancer cells, though this process is poorly understood and previously unexplored in epithelial ovarian cancer (EOC).\nHere, the prognostic and immunomodulatory consequences of baseline ERV expression was assessed in EOC.\nExperimental Design: ERV expression was assessed using EOC transcriptional data from TCGA and from an independent cohort (HH), as well as from untreated or DNMTi-treated EOC cell lines. LASSO logistic regression defined an ERV expression score to predict patient prognosis. Immunohistochemistry (IHC) was conducted on the HH cohort. Combination of DNMTi treatment with γδ T cells was tested in vitro, using EOC cell lines and patient-derived tumor cells.\nResults: ERV expression was found to define clinically relevant subsets of EOC patients. An ERV prognostic score was successfully generated in TCGA and validated in the independent cohort. In EOC patients from this cohort, a high ERV score was associated with better survival (log-rank p=0.0009) and correlated with infiltration of CD8+PD1+ T cells (r=0.46, p=0.0001).\nIn vitro, baseline ERV expression dictates the level of ERV induction in response to DNMTi. Manipulation of ERV expression by DNMTi resulted in improved EOC cell killing by cytotoxic immune cells.\nConclusions: These findings uncover the potential for baseline ERV expression to robustly inform EOC patient prognosis, influence tumor immune infiltration and affect anti-tumor immunity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-16T14:12:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004815","title":"DNA polymerase and mismatch repair deficient cancers exert distinct genome-wide microsatellite signatures","description":null,"abstract":"Whole genome sequencing data for the manuscript: DNA polymerase and mismatch repair deficient cancers exert distinct genome-wide microsatellite signatures","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004816","title":"DNA polymerase and mismatch repair deficient cancers exert distinct genome-wide microsatellite signatures 2","description":null,"abstract":"Whole genome sequencing data for the manuscript: DNA polymerase and mismatch repair deficient cancers exert distinct genome-wide microsatellite signatures","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-16T21:20:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004817","title":"Low Grade Serous Ovarian Cancer Exome Sequencing","description":null,"abstract":"To characterize the most common variants present in LGSOC","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004818","title":"Whole genome sequencing and 3' RNAseq of colorectal cancer samples","description":"Background: Clinical grade whole genome sequencing (cWGS) has the potential to become standard of care within the clinic because of its breadth of coverage and lack of bias towards certain regions of the genome. Colorectal cancer presents a difficult treatment paradigm, with over 40% of patients presenting at diagnosis with metastatic disease. We hypothesised that cWGS coupled with 3’ transcriptome analysis would give new insights into colorectal cancer.Methods: Patients underwent PCR-free whole genome sequencing and alignment and variant calling using a standardised pipeline to output SNVs, indels, SVs and CNAs. Additional insights into mutational signatures and tumour biology were gained by the use of 3’ RNAseq.Results: Fifty-four patients were studied in total. Driver analysis identified the Wnt pathway gene APC as the only consistently mutated driver in colorectal cancer. Alterations in the PI3K/mTOR pathways were seen as previously observed in CRC. Multiple private CNAs, SVs and gene fusions were unique to individual tumours. Approximately 30% of patients had a tumour mutational burden of &gt;10 mutations/Mb of DNA, suggesting suitability for immunotherapy. Conclusions: Clinical whole genome sequencing offers a potential avenue for identification of private genomic variation that may confer sensitivity to targeted agents and offer patients new options for targeted therapies.","abstract":"Background: Clinical grade whole genome sequencing (cWGS) has the potential to become standard of care within the clinic because of its breadth of coverage and lack of bias towards certain regions of the genome. Colorectal cancer presents a difficult treatment paradigm, with over 40% of patients presenting at diagnosis with metastatic disease. We hypothesised that cWGS coupled with 3’ transcriptome analysis would give new insights into colorectal cancer.Methods: Patients underwent PCR-free whole genome sequencing and alignment and variant calling using a standardised pipeline to output SNVs, indels, SVs and CNAs. Additional insights into mutational signatures and tumour biology were gained by the use of 3’ RNAseq.Results: Fifty-four patients were studied in total. Driver analysis identified the Wnt pathway gene APC as the only consistently mutated driver in colorectal cancer. Alterations in the PI3K/mTOR pathways were seen as previously observed in CRC. Multiple private CNAs, SVs and gene fusions were unique to individual tumours. Approximately 30% of patients had a tumour mutational burden of &gt;10 mutations/Mb of DNA, suggesting suitability for immunotherapy. Conclusions: Clinical whole genome sequencing offers a potential avenue for identification of private genomic variation that may confer sensitivity to targeted agents and offer patients new options for targeted therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004819","title":"Long-read and short-read isoform sequencing in breast cancer","description":"The goal of this project was to perform long-read RNA sequencing (LR-seq, PacBio) in combination with short-read RNA-seq for systematic characterization of the isoform diversity in primary breast tumor samples. We sequenced the full-length transcriptomes of 26 breast tumors and 4 normal breast samples.","abstract":"The goal of this project was to perform long-read RNA sequencing (LR-seq, PacBio) in combination with short-read RNA-seq for systematic characterization of the isoform diversity in primary breast tumor samples. We sequenced the full-length transcriptomes of 26 breast tumors and 4 normal breast samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-17T16:42:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004820","title":"Gut metagenomic data of 2,338 Pinggu adults","description":"Here we exploited a Han Chinese population-based cohort with extensive host metadata established in the Pinggu (PG) district of Beijing, and investigated gut microbiota from 2,338 adults (26-76 years) by metagenomic sequencing, revealing associations of the gut microbiota with sex, sex hormones, age, and a number of clinical and metabolic parameters.","abstract":"Here we exploited a Han Chinese population-based cohort with extensive host metadata established in the Pinggu (PG) district of Beijing, and investigated gut microbiota from 2,338 adults (26-76 years) by metagenomic sequencing, revealing associations of the gut microbiota with sex, sex hormones, age, and a number of clinical and metabolic parameters.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-18T03:56:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004821","title":"Integrated Genomic and Transcriptomic Analysis Reveals Unique Characteristics of Hepatic Metastases and Pro-metastatic Role of Complement C1q in Pancreatic Ductal Adenocarcinoma","description":null,"abstract":"Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers due to its high metastasis rate in the liver. However, little is known about the molecular features of hepatic metastases due to difficulty in obtaining fresh tissues and low tumor cellularity.\nResults: We conduct exome sequencing and RNA sequencing for synchronous surgically resected primary tumors and the paired hepatic metastases from 17 hepatic oligometastatic pancreatic ductal adenocarcinoma and validate our findings in specimens from 35 of such cases. The comprehensive analysis of somatic mutations, copy number alterations and gene expressions show high similarity between primary tumors and hepatic metastases. However, hepatic metastases also show unique characteristics, such as a higher degree of 3p21.1 loss, stronger abilities of proliferation, downregulation of epithelial to mesenchymal transition activity and metabolic rewiring. More interesting, altered tumor microenvironments are observed in hepatic metastases, especially a higher proportion of tumor infiltrating M2 macrophage and upregulation of complement cascade. Further experiments demonstrate that expression of C1q increases in primary tumors and hepatic metastases; C1q is mainly produced by M2 macrophage; and C1q promotes migration and invasion of PDAC cells.\nConclusion: Taken together, we find potential factors that contribute to different stages of PDAC metastasis. Our study broadens the understanding of molecular mechanisms driving PDAC metastasis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-18T05:56:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004822","title":"Development and validation of a multi-cancer early detection test.","description":null,"abstract":"The CCGA study is designed to develop and validate a multi-cancer early detection test. Samples from this first sub-study were used in the development phase, where prototype sequencing assays and classifiers were utilized to identify the highest-performing assay with this to move forward into development. This is a subset of 1,400 samples analyzed with whole-genome sequencing.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004823","title":"_Pilot_Optimising_protocols_for_single_cell_profiling_of_SLE_patients","description":"This project involves profiling of blood from 300 SLE patients and 200 healthy volunteers, stimulated with three types of stimuli and profiled at two time points . We are optimising protocols for different stimulations. This will provide us with valuable pilot data that will inform the set up for the rest of the project. In this pilot we will analyse 45 samples to determine the optimum conditions and time points for this study.\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Common immune-mediated diseases such as systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), multiple sclerosis (MS) and others result from hundreds to thousands of variants predisposing to a disease. The vast majority of the disease variants are non-coding and therefore likely influence disease susceptibility through regulating gene expression. Expression quantitative trait locus (eQTL) mapping allows identification of variants that regulate gene expression. The eQTL signals can be colocalised with the GWAS variants and instances where the two signals overlap implicate shared causal variants, and therefore shared molecular mechanisms. This is a powerful approach to link disease variants to downstream genes and pathways, and subsequently to prioritise drug targets. \nThe aim of this pilot study is to use sc-RNA-Seq to understand the functional effect of key genetic variants that have been associated with Systemic Lupus Erythematosus (SLE). We will use transcriptome profiling to generate a single cell eQTL map of gene expression regulation in PBMCs from individuals with SLE.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004824","title":"Reconstruction of human phylogenetic trees using single-cell genome sequencing","description":"The trillions of cells that constitute the human body are developed from a fertilized egg through embryogenesis. However, cellular dynamics and developmental outcomes of embryonic cells remain to be largely unknown due to the technical and ethical challenges. Here we sequenced whole-genomes single-cell-derived clones and various bulk tissues dissected from entire human bodies. Using the discovered somatic mutations as an intrinsic barcode, we reconstructed cellular phylogenetic trees that provide novel insights into early human embryogenesis.","abstract":"The trillions of cells that constitute the human body are developed from a fertilized egg through embryogenesis. However, cellular dynamics and developmental outcomes of embryonic cells remain to be largely unknown due to the technical and ethical challenges. Here we sequenced whole-genomes single-cell-derived clones and various bulk tissues dissected from entire human bodies. Using the discovered somatic mutations as an intrinsic barcode, we reconstructed cellular phylogenetic trees that provide novel insights into early human embryogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-19T23:07:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004825","title":"Molecular response of AML blasts to Aza-treatment.","description":"Azacytidine (Aza) treatment is effective in some patients with acute myeloid leukemia (AML). Clinical observations suggest that DNMT3A-mutant patients represent a subgroup of AML patients that responds particularly well to Aza-treatment. Data coming from a mouse model support this finding and we have already generated molecular data suggesting a molecular pathway involved in Aza-response in DNMT3A-mutant AML patients. We now aim to validate these findings in primary AML-blasts. To this end, we have FACS-sorted blasts from patients with AML prior to and under Aza-treatment and plan to correlate pre-treatment as well as on-treatment methylomes to clinical Aza-response.","abstract":"Azacytidine (Aza) treatment is effective in some patients with acute myeloid leukemia (AML). Clinical observations suggest that DNMT3A-mutant patients represent a subgroup of AML patients that responds particularly well to Aza-treatment. Data coming from a mouse model support this finding and we have already generated molecular data suggesting a molecular pathway involved in Aza-response in DNMT3A-mutant AML patients. We now aim to validate these findings in primary AML-blasts. To this end, we have FACS-sorted blasts from patients with AML prior to and under Aza-treatment and plan to correlate pre-treatment as well as on-treatment methylomes to clinical Aza-response.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-20T15:25:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004826","title":"The genetic structure of Norway","description":"The aim of the present study was to describe the genetic structure of the Norwegian population using genotypes from 6369 unrelated individuals with detailed information about places of residence. Using standard single marker- and haplotype-based approaches, we report evidence of two regions with distinctive patterns of genetic variation, one in the far northeast, and another in the south of Norway, as indicated by fixation indices, haplotype sharing, homozygosity and effective population size. We detect and quantify a component of Uralic Sami ancestry that is enriched in the North. On a finer scale, we find that rates of migration have been affected by topography like mountain ridges. In the broader Scandinavian context, we detect elevated relatedness between the mid- and northern border areas towards Sweden. The main finding of this study is that despite Norway’s long maritime history and as a former Danish territory, the region closest to mainland Europe in the south appears to have been the most isolated region in Norway, highlighting the open sea as a barrier to gene flow into Norway.","abstract":"The aim of the present study was to describe the genetic structure of the Norwegian population using genotypes from 6369 unrelated individuals with detailed information about places of residence. Using standard single marker- and haplotype-based approaches, we report evidence of two regions with distinctive patterns of genetic variation, one in the far northeast, and another in the south of Norway, as indicated by fixation indices, haplotype sharing, homozygosity and effective population size. We detect and quantify a component of Uralic Sami ancestry that is enriched in the North. On a finer scale, we find that rates of migration have been affected by topography like mountain ridges. In the broader Scandinavian context, we detect elevated relatedness between the mid- and northern border areas towards Sweden. The main finding of this study is that despite Norway’s long maritime history and as a former Danish territory, the region closest to mainland Europe in the south appears to have been the most isolated region in Norway, highlighting the open sea as a barrier to gene flow into Norway.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-20T16:00:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004827","title":"Volasertib preclinical activity in high-risk hepatoblastoma","description":"Relapsed and metastatic hepatoblastoma represents an unmet clinical need with limited chemotherapy treatment options. In a chemical screen, we identified volasertib as an agent with in vitro activity, inhibiting hepatoblastoma cell growth while sparing normal hepatocytes. Volasertib targets PLK1 and prevents the progression of mitosis, resulting in eventual cell death. PLK1 is overexpressed in hepatoblastoma biopsies relative to normal liver tissue. As a potential therapeutic strategy, we tested the combination of volasertib and the relapse-related hepatoblastoma chemotherapeutic irinotecan. We found both in vitro and in vivo efficacy of this combination, which may merit further preclinical investigation and exploration for a clinical trial concept.","abstract":"Relapsed and metastatic hepatoblastoma represents an unmet clinical need with limited chemotherapy treatment options. In a chemical screen, we identified volasertib as an agent with in vitro activity, inhibiting hepatoblastoma cell growth while sparing normal hepatocytes. Volasertib targets PLK1 and prevents the progression of mitosis, resulting in eventual cell death. PLK1 is overexpressed in hepatoblastoma biopsies relative to normal liver tissue. As a potential therapeutic strategy, we tested the combination of volasertib and the relapse-related hepatoblastoma chemotherapeutic irinotecan. We found both in vitro and in vivo efficacy of this combination, which may merit further preclinical investigation and exploration for a clinical trial concept.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-20T17:40:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004828","title":"Alveolar Rhabdomyosarcoma case report","description":"Rhabdomyosarcoma (RMS) is a mesenchymal malignancy phenocopying muscle and is among the leading causes of death from childhood cancer. Metastatic alveolar rhabdomyosarcoma is the most aggressive subtype with an 8% five-year disease-free survival rate when a chromosomal fusion is present, and 40% five-year disease-free survival rate when negative for a fusion event. The underlying biology of PAX-fusion negative alveolar rhabdomyosarcoma remains largely unexplored and is exceedingly rare in Li-Fraumeni syndrome patients. Here, we present the case of an 11-year old male with fusion-negative alveolar rhabdomyosarcoma studied at end of life with a comprehensive functional genomics characterization, resulting in identification of potential therapeutic targets for broader investigation.","abstract":"Rhabdomyosarcoma (RMS) is a mesenchymal malignancy phenocopying muscle and is among the leading causes of death from childhood cancer. Metastatic alveolar rhabdomyosarcoma is the most aggressive subtype with an 8% five-year disease-free survival rate when a chromosomal fusion is present, and 40% five-year disease-free survival rate when negative for a fusion event. The underlying biology of PAX-fusion negative alveolar rhabdomyosarcoma remains largely unexplored and is exceedingly rare in Li-Fraumeni syndrome patients. Here, we present the case of an 11-year old male with fusion-negative alveolar rhabdomyosarcoma studied at end of life with a comprehensive functional genomics characterization, resulting in identification of potential therapeutic targets for broader investigation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-20T17:40:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004829","title":"scRNA-seq of HGSC tumor and ascites","description":"Immune regulatory metabolites are key features of the tumor microenvironment (TME), yet with a few notable exceptions, their identities remain largely unknown. We uncovered the immune regulatory metabolic states and metabolomes of sorted tumor and stromal, CD4+, and CD8+ cells from the tumor and ascites of patients with high-grade serous ovarian cancer (HGSC) using high-dimensional flow cytometry and metabolomics supplemented with single cell RNA sequencing. Flow cytometry revealed that tumor cells show a consistently greater uptake of glucose than T cells, but similar mitochondrial activity. Cells within the ascites and tumor had pervasive metabolite differences, with a striking enrichment in 1-methylnicotinamide (MNA) in T cells infiltrating the tumor compared to ascites. Despite the elevated levels of MNA in T cells, the expression of nicotinamide N-methyltransferase, the gene encoding the enzyme that catalyses the transfer of a methyl group from S-adenosylmethionine to nicotinamide, was restricted to fibroblasts and tumor cells. Treatment of T cells with MNA resulted in an increase in T cell-mediated secretion of the tumor promoting cytokine tumor necrosis factor alpha. Thus, the TME-derived metabolite MNA contributes to an alternative and non-cell autonomous mechanism of immune modulation of T cells in HGSC. Collectively, uncovering the tumor-T cell metabolome may reveal metabolic vulnerabilities that can be exploited using T cell-based immunotherapies to treat human cancer.","abstract":"Immune regulatory metabolites are key features of the tumor microenvironment (TME), yet with a few notable exceptions, their identities remain largely unknown. We uncovered the immune regulatory metabolic states and metabolomes of sorted tumor and stromal, CD4+, and CD8+ cells from the tumor and ascites of patients with high-grade serous ovarian cancer (HGSC) using high-dimensional flow cytometry and metabolomics supplemented with single cell RNA sequencing. Flow cytometry revealed that tumor cells show a consistently greater uptake of glucose than T cells, but similar mitochondrial activity. Cells within the ascites and tumor had pervasive metabolite differences, with a striking enrichment in 1-methylnicotinamide (MNA) in T cells infiltrating the tumor compared to ascites. Despite the elevated levels of MNA in T cells, the expression of nicotinamide N-methyltransferase, the gene encoding the enzyme that catalyses the transfer of a methyl group from S-adenosylmethionine to nicotinamide, was restricted to fibroblasts and tumor cells. Treatment of T cells with MNA resulted in an increase in T cell-mediated secretion of the tumor promoting cytokine tumor necrosis factor alpha. Thus, the TME-derived metabolite MNA contributes to an alternative and non-cell autonomous mechanism of immune modulation of T cells in HGSC. Collectively, uncovering the tumor-T cell metabolome may reveal metabolic vulnerabilities that can be exploited using T cell-based immunotherapies to treat human cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-23T17:20:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004830","title":"MicroRNAs signatures from CSF extracellular vesicles of Parkinson’s Disease patients","description":null,"abstract":"The diagnosis of Parkinson’s disease (PD) lacks precision and occurs relatively late in disease progression. MicroRNAs are epigenetic regulators that have been used as biomarkers in various medical fields. Here, we used small RNA sequencing to quantify the microRNAome of extracellular vesicles isolated from human cerebrospinal fluid (CSF) of PD and control subjects (CTR) aiming to identify a microRNA-based signature for PD.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-23T18:35:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004831","title":"Immunological hallmarks for clinical response to BCG in bladder cancer","description":"Intravesical Bacillus Calmette-Guerin (BCG) is an effective immunotherapy for non-muscle invasive bladder cancer (NMIBC). However, recurrence and progression remain frequent warranting deeper insights into its mechanism. We herein comprehensively profiled blood and tissues obtained from NMIBC patients before, during and after BCG treatment using cytometry by time-of-flight (CyTOF) and RNA sequencing to identify the key immune subsets crucial for anti-tumour activity.","abstract":"Intravesical Bacillus Calmette-Guerin (BCG) is an effective immunotherapy for non-muscle invasive bladder cancer (NMIBC). However, recurrence and progression remain frequent warranting deeper insights into its mechanism. We herein comprehensively profiled blood and tissues obtained from NMIBC patients before, during and after BCG treatment using cytometry by time-of-flight (CyTOF) and RNA sequencing to identify the key immune subsets crucial for anti-tumour activity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004832","title":"OpACIN-neo – A Multicenter Phase 2 Study to identify the Optimal neo-Adjuvant Combination scheme of Ipilimumab and Nivolumab – Whole exome sequencing","description":"The outcome of patients with macroscopic stage III melanoma is poor. Neoadjuvant treatment with ipilimumab plus nivolumab at the standard dosing schedule induced pathological responses in a high proportion of patients in two small independent early-phase trials. However, toxicity of the standard ipilimumab plus nivolumab dosing schedule was high, preventing its broader clinical use. The aim of the OpACIN-neo study (NCT02977052) to identify a dosing schedule of ipilimumab plus nivolumab that is less toxic but equally effective. 86 patients with macroscopic stage III melanoma were randomised to one of three dosing schedules: arm A, two cycles of ipilimumab 3 mg/kg plus nivolumab 1 mg/kg once every 3 weeks; arm B, two cycles of ipilimumab 1 mg/kg plus nivolumab 3 mg/kg once every 3 weeks; or arm C, two cycles of ipilimumab 3 mg/kg once every 3 weeks directly followed by two cycles of nivolumab 3mg/kg once every 2 weeks. Within the first 12 weeks, grade 3–4 immune-related adverse events were observed in 12 (40%) of 30 patients in group A, six (20%) of 30 in group B, and 13 (50%) of 26 in group C. Pathological responses occurred in 24 (80%) patients in group A, 23 (77%) in group B, and 17 (65%) in group C. The 2-year estimated relapse-free survival was 84% for all patients, 97% for patients achieving a pathologic response and 36% for nonresponders (p&lt;0.001). High tumor mutational burden (TMB) and high interferon-gamma-related gene expression signature score (IFN-γ score) were associated with pathologic response and low risk of relapse; pathologic response rate (pRR) was 100% in patients with high IFN-γ score/high TMB, patients with high IFN-γ score/low TMB or low IFN-γ score/high TMB had pRRs of 91% and 88%; while patients with low IFN-γ score/low TMB had a pRR of only 39%. These data demonstrate long-term benefit in patients with a pathologic response and show the predictive potential of TMB and IFN-γ score.","abstract":"The outcome of patients with macroscopic stage III melanoma is poor. Neoadjuvant treatment with ipilimumab plus nivolumab at the standard dosing schedule induced pathological responses in a high proportion of patients in two small independent early-phase trials. However, toxicity of the standard ipilimumab plus nivolumab dosing schedule was high, preventing its broader clinical use. The aim of the OpACIN-neo study (NCT02977052) to identify a dosing schedule of ipilimumab plus nivolumab that is less toxic but equally effective. 86 patients with macroscopic stage III melanoma were randomised to one of three dosing schedules: arm A, two cycles of ipilimumab 3 mg/kg plus nivolumab 1 mg/kg once every 3 weeks; arm B, two cycles of ipilimumab 1 mg/kg plus nivolumab 3 mg/kg once every 3 weeks; or arm C, two cycles of ipilimumab 3 mg/kg once every 3 weeks directly followed by two cycles of nivolumab 3mg/kg once every 2 weeks. Within the first 12 weeks, grade 3–4 immune-related adverse events were observed in 12 (40%) of 30 patients in group A, six (20%) of 30 in group B, and 13 (50%) of 26 in group C. Pathological responses occurred in 24 (80%) patients in group A, 23 (77%) in group B, and 17 (65%) in group C. The 2-year estimated relapse-free survival was 84% for all patients, 97% for patients achieving a pathologic response and 36% for nonresponders (p&lt;0.001). High tumor mutational burden (TMB) and high interferon-gamma-related gene expression signature score (IFN-γ score) were associated with pathologic response and low risk of relapse; pathologic response rate (pRR) was 100% in patients with high IFN-γ score/high TMB, patients with high IFN-γ score/low TMB or low IFN-γ score/high TMB had pRRs of 91% and 88%; while patients with low IFN-γ score/low TMB had a pRR of only 39%. These data demonstrate long-term benefit in patients with a pathologic response and show the predictive potential of TMB and IFN-γ score.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-24T07:26:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004833","title":"OpACIN-neo – A Multicenter Phase 2 Study to identify the Optimal neo-Adjuvant Combination scheme of Ipilimumab and Nivolumab – RNA sequencing","description":"The outcome of patients with macroscopic stage III melanoma is poor. Neoadjuvant treatment with ipilimumab plus nivolumab at the standard dosing schedule induced pathological responses in a high proportion of patients in two small independent early-phase trials. However, toxicity of the standard ipilimumab plus nivolumab dosing schedule was high, preventing its broader clinical use. The aim of the OpACIN-neo study (NCT02977052) to identify a dosing schedule of ipilimumab plus nivolumab that is less toxic but equally effective. 86 patients with macroscopic stage III melanoma were randomised to one of three dosing schedules: arm A, two cycles of ipilimumab 3 mg/kg plus nivolumab 1 mg/kg once every 3 weeks; arm B, two cycles of ipilimumab 1 mg/kg plus nivolumab 3 mg/kg once every 3 weeks; or arm C, two cycles of ipilimumab 3 mg/kg once every 3 weeks directly followed by two cycles of nivolumab 3mg/kg once every 2 weeks. Within the first 12 weeks, grade 3–4 immune-related adverse events were observed in 12 (40%) of 30 patients in group A, six (20%) of 30 in group B, and 13 (50%) of 26 in group C. Pathological responses occurred in 24 (80%) patients in group A, 23 (77%) in group B, and 17 (65%) in group C. The 2-year estimated relapse-free survival was 84% for all patients, 97% for patients achieving a pathologic response and 36% for nonresponders (p&lt;0.001). High tumor mutational burden (TMB) and high interferon-gamma-related gene expression signature score (IFN-γ score) were associated with pathologic response and low risk of relapse; pathologic response rate (pRR) was 100% in patients with high IFN-γ score/high TMB, patients with high IFN-γ score/low TMB or low IFN-γ score/high TMB had pRRs of 91% and 88%; while patients with low IFN-γ score/low TMB had a pRR of only 39%. These data demonstrate long-term benefit in patients with a pathologic response and show the predictive potential of TMB and IFN-γ score.","abstract":"The outcome of patients with macroscopic stage III melanoma is poor. Neoadjuvant treatment with ipilimumab plus nivolumab at the standard dosing schedule induced pathological responses in a high proportion of patients in two small independent early-phase trials. However, toxicity of the standard ipilimumab plus nivolumab dosing schedule was high, preventing its broader clinical use. The aim of the OpACIN-neo study (NCT02977052) to identify a dosing schedule of ipilimumab plus nivolumab that is less toxic but equally effective. 86 patients with macroscopic stage III melanoma were randomised to one of three dosing schedules: arm A, two cycles of ipilimumab 3 mg/kg plus nivolumab 1 mg/kg once every 3 weeks; arm B, two cycles of ipilimumab 1 mg/kg plus nivolumab 3 mg/kg once every 3 weeks; or arm C, two cycles of ipilimumab 3 mg/kg once every 3 weeks directly followed by two cycles of nivolumab 3mg/kg once every 2 weeks. Within the first 12 weeks, grade 3–4 immune-related adverse events were observed in 12 (40%) of 30 patients in group A, six (20%) of 30 in group B, and 13 (50%) of 26 in group C. Pathological responses occurred in 24 (80%) patients in group A, 23 (77%) in group B, and 17 (65%) in group C. The 2-year estimated relapse-free survival was 84% for all patients, 97% for patients achieving a pathologic response and 36% for nonresponders (p&lt;0.001). High tumor mutational burden (TMB) and high interferon-gamma-related gene expression signature score (IFN-γ score) were associated with pathologic response and low risk of relapse; pathologic response rate (pRR) was 100% in patients with high IFN-γ score/high TMB, patients with high IFN-γ score/low TMB or low IFN-γ score/high TMB had pRRs of 91% and 88%; while patients with low IFN-γ score/low TMB had a pRR of only 39%. These data demonstrate long-term benefit in patients with a pathologic response and show the predictive potential of TMB and IFN-γ score.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-24T07:26:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004834","title":"PBMC_dual_10X_kit","description":"Dual snRNAseq and ATACseq of replicate PBMC samples for 10X beta testing.","abstract":"Dual snRNAseq and ATACseq of replicate PBMC samples for 10X beta testing. The sample is also part of a benchmarking study for different ATAC-seq protocols coordinated by Holger Heyn in Barcelona. Two replicates of sample of PBMCs (joint sample from two individuals) will be sequenced.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-24T12:03:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004835","title":"Differential gene expression in the colon mucosa of irritable bowel syndrome patients with mixed type symptoms","description":"The aim of this study is to characterize the pathophysiology of the irritable bowel syndrome (IBS) on the functional level and in parallel on the gene expression level. For this purpose RNAseq of mucosal biopsies was performed. The data from the differential expression analysis will be further processed by Ingenuity Pathway Analysis (IPA) software to gather Information on activated or inhibited signaling pathways in the disease.","abstract":"The aim of this study is to characterize the pathophysiology of the irritable bowel syndrome (IBS) on the functional level and in parallel on the gene expression level. For this purpose RNAseq of mucosal biopsies was performed. The data from the differential expression analysis will be further processed by Ingenuity Pathway Analysis (IPA) software to gather Information on activated or inhibited signaling pathways in the disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-24T12:13:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004836","title":"Effect_of_FAM50_knockout_on_the_transcriptome","description":"A knockout clone has been generated for both FAM50A and FAM50B; knockout of the other gene is then performed and the transcriptome is analysed to look at the effect of dual gene loss.","abstract":"A knockout clone has been generated for both FAM50A and FAM50B; knockout of the other gene is then performed and the transcriptome is analysed to look at the effect of dual gene loss.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-24T15:23:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004837","title":"Inherited CD28 deficiency in otherwise healthy patients with disseminated warts and giant horns","description":null,"abstract":"This study presents the analysis of a patient with the HPV-2-driven “tree man” phenotype, and two of his distant relatives with unusually severe HPV4-driven warts. All three patients are homozygous for a private CD28 variant. The data available here are 10X Genomics 3' scRNA-seq data of the three patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-24T17:03:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004838","title":"WGSPD Project 3 - Genomic Strategies to Identify High-impact Psychiatric Risk Variants","description":null,"abstract":"To comprehensively detect rare variants and demonstrate their effect on psychiatric phenotypes will require WGS of tens of thousands of samples, studies that are still impractically expensive. We propose a plan that can identify variants contributing to BP, SCZ, and their endophenotypes by WGS of over 5,000 samples and then imputation of the novel variants into tens of thousands of samples for association analyses.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-24T20:44:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004839","title":"An essential role for MYB in driving oncogenic EVI1 expression in enhancer-rearranged leukemias","description":"In acute myeloid leukemia (AML) with inv(3)(q21;q26) or t(3;3)(q21;q26), a translocated GATA2 enhancer drives oncogenic expression of EVI1. We generated an EVI1-GFP AML model and applied an unbiased CRISPR/Cas9 enhancer scan to uncover sequence motifs essential for EVI1 transcription. Using this approach, we pinpoint a single regulatory element in the translocated GATA2 enhancer that is critically required for aberrant EVI1 expression while being dispensable for GATA2 expression from its endogenous locus. This element contains a DNA binding motif for the transcription factor MYB that heavily occupies this site specifically at the translocated allele. MYB knockout as well as peptidomimetic blockade of p300-dependent MYB function resulted in downregulation of EVI1 but not of GATA2. Targeting MYB or mutating its DNA-binding motif within the GATA2 enhancer resulted in myeloid differentiation and cell death, suggesting that interference with MYB-driven EVI1 transcription provides a potential entry point for therapy of inv(3)/t(3;3) AMLs.","abstract":"In acute myeloid leukemia (AML) with inv(3)(q21;q26) or t(3;3)(q21;q26), a translocated GATA2 enhancer drives oncogenic expression of EVI1. We generated an EVI1-GFP AML model and applied an unbiased CRISPR/Cas9 enhancer scan to uncover sequence motifs essential for EVI1 transcription. Using this approach, we pinpoint a single regulatory element in the translocated GATA2 enhancer that is critically required for aberrant EVI1 expression while being dispensable for GATA2 expression from its endogenous locus. This element contains a DNA binding motif for the transcription factor MYB that heavily occupies this site specifically at the translocated allele. MYB knockout as well as peptidomimetic blockade of p300-dependent MYB function resulted in downregulation of EVI1 but not of GATA2. Targeting MYB or mutating its DNA-binding motif within the GATA2 enhancer resulted in myeloid differentiation and cell death, suggesting that interference with MYB-driven EVI1 transcription provides a potential entry point for therapy of inv(3)/t(3;3) AMLs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-25T08:18:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004840","title":"Immunogenomic correlates of response to combination immune checkpoint blockade in advanced sarcoma","description":"Sarcomas encompass a rare but highly diverse set of tumor malignancies, contributing disproportionately to years of life lost. Immune checkpoint blockade (ICB) has been successful across various tumor types; however, their efficacy and predictability in sarcomas remain unknown. We conducted a translational study using pre- and on-treatment tumor biopsies collected prospectively on a Phase II clinical trial evaluating the role of combination durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4) in 57 patients, enrolled across multiple histologies of metastatic sarcoma. Amongst those potential molecular correlates of response analyzed, elevated levels of B-cells both at the transcriptome and through validation staining were most significantly correlated with response. This B-cell enrichment was further validated in an independent ICB treated cohort with matched molecular data. Responsive tumors were also associated with higher levels of T-cell repertoire (TCR) richness indicating a strong association of diversity in the TCR of responders. This work frames the potential molecular features of the tumor microenvironment that may influence response in ICB treated sarcomas.","abstract":"Sarcomas encompass a rare but highly diverse set of tumor malignancies, contributing disproportionately to years of life lost. Immune checkpoint blockade (ICB) has been successful across various tumor types; however, their efficacy and predictability in sarcomas remain unknown. We conducted a translational study using pre- and on-treatment tumor biopsies collected prospectively on a Phase II clinical trial evaluating the role of combination durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4) in 57 patients, enrolled across multiple histologies of metastatic sarcoma. Amongst those potential molecular correlates of response analyzed, elevated levels of B-cells both at the transcriptome and through validation staining were most significantly correlated with response. This B-cell enrichment was further validated in an independent ICB treated cohort with matched molecular data. Responsive tumors were also associated with higher levels of T-cell repertoire (TCR) richness indicating a strong association of diversity in the TCR of responders. This work frames the potential molecular features of the tumor microenvironment that may influence response in ICB treated sarcomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004841","title":"Molecular profiling of an AML case following treatment with a BCL2 inhibitor","description":"Molecular profiling of a single AML case. Exome sequencing was performed at diagnosis and after treatment with conventional chemotherapy and BCL2i. Some samples required whole genome amplification. Data will be made available to researchers upon completion of a data transfer agreement; use is restricted to ethically approved research focused on haematological malignancy, and precludes germline analysis.","abstract":"Molecular profiling of a single AML case. Exome sequencing was performed at diagnosis and after treatment with conventional chemotherapy and BCL2i. Some samples required whole genome amplification. Data will be made available to researchers upon completion of a data transfer agreement; use is restricted to ethically approved research focused on haematological malignancy, and precludes germline analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-26T01:53:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004842","title":"Molecular profiling of MBD4-deficient colorectal polyps","description":"Exome sequencing was performed on DNA samples extracted from colorectal polyps from a case with constitutive MBD4-deficiency. Tissue was extracted from Formalin Fixed Paraffin Embedded tissue blocks. Multiregion sequencing was performed on some samples. Data is made available for ethically approved research upon completion of a data transfer agreement, which includes restrictions on the disclosure of germline variants.","abstract":"Exome sequencing was performed on DNA samples extracted from colorectal polyps from a case with constitutive MBD4-deficiency. Tissue was extracted from Formalin Fixed Paraffin Embedded tissue blocks. Multiregion sequencing was performed on some samples. Data is made available for ethically approved research upon completion of a data transfer agreement, which includes restrictions on the disclosure of germline variants.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004843","title":"Immune trajectory of response and adverse effect in immunotherapy-treated hepatocellular carcinoma","description":"Whilst anti-PD1 immune checkpoint blockade (ICB) has revolutionised treatment for many cancers, its response rates in hepatocellular carcinoma (HCC) remain modest, coupled with common incidences of immune-related adverse events (irAEs). To identify biomarkers and decipher the mechanisms for response and irAEs, we performed multi-dimensional immunoprofiling on peripheral blood and tissue collected before and during anti-PD1 ICB treatment from HCC patients. Single-cell analyses enabled us to identify peripheral biomarkers, in particular, CD11c+ antigen-presenting cells with varying degrees of HLA-DR expression and CD8 effector memory (EM) T cells with CXCR3 tissue-homing capability that are associated with both response and irAEs. We also dissected the mechanisms behind how these immune subsets interface between response and toxicity, showing their intersecting yet diverging trajectories leading to these distinct clinical fates. This study offers new insights on the mechanisms and potentially novel strategies to enhance response and ameliorate irAEs in cancer immunotherapy.","abstract":"Whilst anti-PD1 immune checkpoint blockade (ICB) has revolutionised treatment for many cancers, its response rates in hepatocellular carcinoma (HCC) remain modest, coupled with common incidences of immune-related adverse events (irAEs). To identify biomarkers and decipher the mechanisms for response and irAEs, we performed multi-dimensional immunoprofiling on peripheral blood and tissue collected before and during anti-PD1 ICB treatment from HCC patients. Single-cell analyses enabled us to identify peripheral biomarkers, in particular, CD11c+ antigen-presenting cells with varying degrees of HLA-DR expression and CD8 effector memory (EM) T cells with CXCR3 tissue-homing capability that are associated with both response and irAEs. We also dissected the mechanisms behind how these immune subsets interface between response and toxicity, showing their intersecting yet diverging trajectories leading to these distinct clinical fates. This study offers new insights on the mechanisms and potentially novel strategies to enhance response and ameliorate irAEs in cancer immunotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-27T09:11:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004844","title":"Single Cell MK and HSC sequencing","description":"In the current understanding of adult bone marrow hematopoiesis, megakaryocytes (MKs) originate from cells immuno-phenotypically indistinguishable from  hematopoietic stem cells (HSCs), bypassing intermediate progenitors. Here, we use single cell RNA sequencing to characterize HSCs and MKs from human bone marrow, to investigate MK lineage commitment and maturation.","abstract":"In the current understanding of adult bone marrow hematopoiesis, megakaryocytes (MKs) originate from cells immuno-phenotypically indistinguishable from  hematopoietic stem cells (HSCs), bypassing intermediate progenitors. Here, we use single cell RNA sequencing to characterize HSCs and MKs from human bone marrow, to investigate MK lineage commitment and maturation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-27T10:28:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004845","title":"Genomic mapping in malignant pleural mesothelioma","description":null,"abstract":"Background: Malignant pleural mesothelioma (MPM) is an aggressive malignancy with limited effective therapies. \nMethods: To identify therapeutic targets we integrated SNP genotyping, sequencing and transcriptomics from tumours and low-passage patient-derived cells. \nResults: Previously unrecognised losses of SUFU, observed in 21% tumours, resulted in disordered expression of Hedgehog pathway transcripts and genes from the T-cell synapse, including VISTA. Co-deletion of Interferon type I genes and CDKN2A was present in half of tumours and was a predictor of poor survival.  We found previously unrecognised deletions in RB1 in 26% of cases and show sub-micromolar responses to downstream PLK1, CHEK1 and Aurora Kinase inhibitors in primary MPM cells. Defects in Hippo pathways that included RASSF7 amplification and NF2 or LATS1/2 mutations were present in 50% of tumours and were accompanied by micromolar responses to the YAP1 inhibitor Verteporfin. \nConclusions: The results suggest multiple new therapeutic avenues in MPM and include targets and biomarkers for immunotherapy.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004846","title":"Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts-BRCA-EurOPDX NKI","description":null,"abstract":"Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical\nstudies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution\nduring PDX engraftment and propagation, impacting the accuracy of PDX modeling of human\ncancer. Here we exhaustively analyze copy number alterations (CNAs) in 1451 PDX and matched\npatient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing\nand microarray data displayed substantially higher resolution and dynamic range than gene\nexpression-based inferences, and they also showed strong CNA conservation from PTs through\nlate-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-\nlate trios confirmed high-resolution CNA retention. We observed no significant enrichment of\ncancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between\npatient and PDX tumors were comparable to variations in multi-region samples within patients.\nOur study demonstrates the lack of systematic copy number evolution driven by the PDX mouse\nhost.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004847","title":"Circulating Tumor DNA in Checkpoint Inhibitor treated Lung Cancer","description":"BackgroundImmune checkpoint inhibitors (ICI) are increasingly used to treat non-small cell lung cancer (NSCLC) and there is a critical need for novel predictive/prognostic biomarkers. We evaluated whether dynamics of circulating tumor (ctDNA) can identify NSCLC patients who benefit from single agent ICI.MethodsCirculating cell-free DNA (cfDNA) from 177 patients was analyzed prior ICI and at first treatment evaluation using a Commercial 77-gene panel. We performed de novo mutation calling and corrected for variants related clonal hematopoiesis. ctDNA changes were evaluated as predictors of tumor response estimated with PET/diagnostic CT and survival.ResultsMutations were detected in 159 of 174 (91.4%) analyzable patients. Most responders presented decreasing ctDNA levels, while non-responders had mixed molecular responses. Patients with a &gt;50% molecular ctDNA decrease or no detectable ctDNA demonstrated improved PFS (5.9 versus 1.8 months; HR 0.49, 95%CI, 0.35-0.67, P &lt; .001), and OS (18.9 versus 9.9 months; HR 0.41, 95%CI, 0.30-0.57, P &lt; .001) compared to patients not achieving these endpoints. Clearance of mutations (and no detected ctDNA) had a similar effect (PFS HR 0.45, 95%CI, 0.32-0.61, P &lt; .001; OS 0.37,95%CI, 0.27-0.52, P &lt; .001) compared to patients having stable or additional mutations. After adjusting for clinical factors both &gt;50% ctDNA decrease (HR 0.4, 95% CI, 0.3-0.6, P &lt; .001) and clearance of mutations (HR 0.42, 95% CI, 0.3-0.6, P &lt; .001) remained independent predictors for PFS and OS.ConclusionsctDNA testing reveals significant prognostic albeit not predictive information in ICI treated advanced NSCLC. This relevant information can be obtained with a commercial easy-to-implement ctDNA test that will facilitate extensive testing.","abstract":"BackgroundImmune checkpoint inhibitors (ICI) are increasingly used to treat non-small cell lung cancer (NSCLC) and there is a critical need for novel predictive/prognostic biomarkers. We evaluated whether dynamics of circulating tumor (ctDNA) can identify NSCLC patients who benefit from single agent ICI.MethodsCirculating cell-free DNA (cfDNA) from 177 patients was analyzed prior ICI and at first treatment evaluation using a Commercial 77-gene panel. We performed de novo mutation calling and corrected for variants related clonal hematopoiesis. ctDNA changes were evaluated as predictors of tumor response estimated with PET/diagnostic CT and survival.ResultsMutations were detected in 159 of 174 (91.4%) analyzable patients. Most responders presented decreasing ctDNA levels, while non-responders had mixed molecular responses. Patients with a &gt;50% molecular ctDNA decrease or no detectable ctDNA demonstrated improved PFS (5.9 versus 1.8 months; HR 0.49, 95%CI, 0.35-0.67, P &lt; .001), and OS (18.9 versus 9.9 months; HR 0.41, 95%CI, 0.30-0.57, P &lt; .001) compared to patients not achieving these endpoints. Clearance of mutations (and no detected ctDNA) had a similar effect (PFS HR 0.45, 95%CI, 0.32-0.61, P &lt; .001; OS 0.37,95%CI, 0.27-0.52, P &lt; .001) compared to patients having stable or additional mutations. After adjusting for clinical factors both &gt;50% ctDNA decrease (HR 0.4, 95% CI, 0.3-0.6, P &lt; .001) and clearance of mutations (HR 0.42, 95% CI, 0.3-0.6, P &lt; .001) remained independent predictors for PFS and OS.ConclusionsctDNA testing reveals significant prognostic albeit not predictive information in ICI treated advanced NSCLC. This relevant information can be obtained with a commercial easy-to-implement ctDNA test that will facilitate extensive testing.","study_type":"Other","pubmed_ids":[34994642],"external_links":null,"is_released":true,"released_date":"2020-11-30T08:32:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004848","title":"Genome methylation accurately predicts neuroendocrine tumor origin","description":null,"abstract":"Purpose: The primary origin of neuroendocrine tumor metastases can be difficult to determine by histopathology alone, but is critical for therapeutic decision making. DNA methylation-based profiling is now routinely used in the diagnostic workup of brain tumors. This has been enabled by the availability of cost-efficient array-based platforms. We have extended these efforts to augment histopathological diagnosis in neuroendocrine tumors. \nExperimental Design and Results: We compiled data of 69 small-intestinal, pulmonary, and pancreatic neuroendocrine tumors. These data were used to build a ridge regression calibrated random forest classification algorithm (NEN-ID) that predicts the origin of tumor samples with high accuracy (&gt; 95%). The model was validated during 3x3 nested cross validation and tested in a local (n=26) and external (n=172) cohort. In addition, we show that our diagnostic approach is robust across a range of possible confounding experimental parameters such as tumor purity and array quality. A software infrastructure and online user interface was built to make the model available to the scientific community.\nConclusions: This DNA methylation-based prediction model can be used in the workup for patients with neuroendocrine tumors of unknown primary. To facilitate validation and clinical implementation, we provide a user-friendly, publicly available web-based version of NEN-ID.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004849","title":"Dissecting alternative lengthening of telomeres in childhood neuroblastoma from genome to proteome","description":null,"abstract":"Multi-omics analysis of ALT-positive neuroblastoma tumors","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004850","title":"The Acquisition of Molecular Drivers in Pediatric Therapy-Related Myeloid Neoplasms","description":"Pediatric therapy-related myeloid neoplasms (tMN) occur in children after exposure to cytotoxic therapy and have a dismal prognosis1-4. The somatic and germline genomic alterations that drive these myeloid neoplasms in children and how they arise have yet to be comprehensively described. We use whole exome, whole genome, and/or RNA sequencing to characterize the genomic profile of 85 pediatric tMN cases (tMDS: n=29, tAML: n=56). Our data show that Ras/MAPK pathway mutations, alterations in RUNX1 or TP53, and KMT2A rearrangements are frequent somatic drivers, and we identify cases with aberrant MECOM expression secondary to enhancer hijacking. Unlike adults with tMN5-7, we find no evidence of pre-existing minor tMN clones (including those with TP53 mutations), but rather the majority of cases were unrelated clones arising as a consequence of cytotoxic therapy. These studies also uncover rare cases of lineage switch disease rather than true secondary neoplasms.","abstract":"Pediatric therapy-related myeloid neoplasms (tMN) occur in children after exposure to cytotoxic therapy and have a dismal prognosis1-4. The somatic and germline genomic alterations that drive these myeloid neoplasms in children and how they arise have yet to be comprehensively described. We use whole exome, whole genome, and/or RNA sequencing to characterize the genomic profile of 85 pediatric tMN cases (tMDS: n=29, tAML: n=56). Our data show that Ras/MAPK pathway mutations, alterations in RUNX1 or TP53, and KMT2A rearrangements are frequent somatic drivers, and we identify cases with aberrant MECOM expression secondary to enhancer hijacking. Unlike adults with tMN5-7, we find no evidence of pre-existing minor tMN clones (including those with TP53 mutations), but rather the majority of cases were unrelated clones arising as a consequence of cytotoxic therapy. These studies also uncover rare cases of lineage switch disease rather than true secondary neoplasms.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-30T14:49:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004851","title":"AGECAN - Interespecies conservation of brain specific DNA methylation in aging and cancer","description":null,"abstract":"Aging is one of the main risk factors associated with the development of cancer. These two processes have been extensively investigated from the epigenetic perspective and consequently analogous epigenetic alterations have been identified for both, providing explanations on the possible molecular links between them. However, there is a need to study aging- and cancer-associated epigenetic patterns in a systematic manner to facilitate an integrated comparison between the two processes. In addition, it is essential to also confirm whether aging- and cancer-associated epigenetic alterations are equivalent in human and mouse models, as the latter are the main experimental proxy of human biology.In this study we sought to perform a systematic, integrated and intercomparable analysis of the DNA methylation dynamics associated to cancer and aging in both human and mouse. To this end, we profiled the brain methylomes of young and old, normal and tumoral brain samples from human and mouse by reduced-representation bisulfite sequencing (RRBS), which provided a robust and interspecies-comparable platform for these type of analyses. This data set only contains files involving human specimens. Accompanying mouse data can be downloaded from the ENA database under the accession number PRJEB41460.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-11-30T17:12:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004852","title":"Tumor HTG EdgeSeq from metastatic castrate resistant prostate cancer","description":"This dataset contains tumor bulk HTG EdgeSeq from patients with metastatic castrate resistant prostate cancer. RNA libraries were prepared following manufacturer's user guide (HTG Molecular Diagnostics). Each library was sequenced in HTG EdgeSeq system.","abstract":"This dataset contains tumor bulk HTG EdgeSeq from patients with metastatic castrate resistant prostate cancer. RNA libraries were prepared following manufacturer's user guide (HTG Molecular Diagnostics). Each library was sequenced in HTG EdgeSeq system.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-01T02:09:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004853","title":"Identifying_and_characterising_the_phenotypic_consequences_of_genetic_perturbation_of_GMPR_and_CHAC2_in_cellular_models","description":"We have generated human iPSC lines with heterozygous and homozygous knockouts of the GMPR gene and modifications in the CHAC2 gene through CRISPR/Cas9-mediated genome editing and have successfully differentiated these lines into red blood cells (RBCs).\nTo provide a comprehensive assessment of the phenotypic changes in RBCs derived from engineered hiPSCs we will profile genome-wide gene expression changes using RNA-seq in the edited RBC lines. Transcriptional changes will be measured in 2 lines of each wild-type, heterozygous, and homozygous null deletions of GMPR at day 5, 10 and 15 of erythropoiesis to capture distinct cellular states. For all lines, we will also include the undifferentiated iPSCs as reference. CHAC2 lines will only be sequenced in the undifferentiated state.\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"We have generated human iPSC lines with heterozygous and homozygous knockouts of the GMPR gene and modifications in the CHAC2 gene through CRISPR/Cas9-mediated genome editing and have successfully differentiated these lines into red blood cells (RBCs).\nTo provide a comprehensive assessment of the phenotypic changes in RBCs derived from engineered hiPSCs we will profile genome-wide gene expression changes using RNA-seq in the edited RBC lines. Transcriptional changes will be measured in 2 lines of each wild-type, heterozygous, and homozygous null deletions of GMPR at day 5, 10 and 15 of erythropoiesis to capture distinct cellular states. For all lines, we will also include the undifferentiated iPSCs as reference. CHAC2 lines will only be sequenced in the undifferentiated state.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004854","title":"Neuroinflammation_scRNAseq","description":"The goal of this project is to understand the causal link between cellular processes and Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. This study will use large scale mapping experiments to identify expression QTLs using variation from the HipSci resource of cell lines, and scRNAseq. We will then employ colocalization analysis (with for example AD/PD GWAS/GWAX data from OTAR037 and publically available data (Nicolas et al. 2018)) to map loci where the same causal genetic signal drives both disease risk and variation in a core microglial cell function.","abstract":"he goal of this project is to understand the causal link between cellular processes and Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. This study will use large scale mapping experiments to identify expression QTLs using variation from the HipSci resource of cell lines, and scRNAseq. We will then employ colocalization analysis (with for example AD/PD GWAS/GWAX data from OTAR037 and publically available data (Nicolas et al. 2018)) to map loci where the same causal genetic signal drives both disease risk and variation in a core microglial cell function.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004855","title":"Exome sequencing of multiple myeloma measurable residual disease","description":null,"abstract":"Multiple myeloma (MM) measurable residual disease (MRD) persisting after treatment is an adverse prognostic factor for progression-free survival (PFS) and overall survival.  Acquisition of genomic mutations in the remaining clonal aberrant plasma cells (A-PCs) is likely linked to the development of drug resistance and disease relapse. Thus, personalising treatment based on the genomic profile of MRD could be highly beneficial and ultimately increase patients’ survival. However, while large-scale sequencing studies have characterised the genome of many malignancies, including multiple myeloma, the genomic mutations acquired by MM MRD are at the beginning of the investigation. Here, we set up a comprehensive genomic analysis based on whole exome sequencing (WES) of amplified A-PC DNA to identify genomic mutations characteristics for MM MRD and explore if they could mediate drug response, resistance or disease progression.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004856","title":"Shwachman-Diamond syndrome sequencing study","description":null,"abstract":"To define the mechanistic basis of clonal hematopoiesis in Shwachman-Diamond syndrome (SDS), we investigated somatic mutations acquired by patients with SDS followed longitudinally.  This study consisted of three sequencing datasets: whole exome sequencing in a discovery cohort of patients, followed by deep-targeted sequencing in all patients in the North American SDS registry.  We further analyzed a subset of bone marrow samples by single cell sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-01T14:18:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004857","title":"Comprehensive genomic and transcriptomic analysis of three synchronous primary tumours and a recurrence from a head and neck cancer patient","description":"Synchronous primary malignancies occur in a small proportion of head and neck squamous cell carcinoma patients. Here, we analysed three synchronous primaries and a recurrence from one patient, by comparing the genomic and transcriptomic profiles among the tumour samples and determining the recurrence origin. We found remarkable levels of heterogeneity among the primary tumours, and through the patterns of shared mutations, we traced the origin of the recurrence. Interestingly, the patient carried germline variants which might have predisposed him to carcinogenesis, together with a history of alcohol and tobacco consumption. Mutational signature analysis confirmed the impact of alcohol exposure, with Signature 16 present in all tumour samples. Characterisation of immune cell infiltration highlighted an immunosuppressive environment in all samples, which exceeded the potential activity of T cells. Studies such as the one described here have important clinical value and contribute to personalised treatment decisions for patients with synchronous primaries and matched recurrences.","abstract":"Synchronous primary malignancies occur in a small proportion of head and neck squamous cell carcinoma patients. Here, we analysed three synchronous primaries and a recurrence from one patient, by comparing the genomic and transcriptomic profiles among the tumour samples and determining the recurrence origin. We found remarkable levels of heterogeneity among the primary tumours, and through the patterns of shared mutations, we traced the origin of the recurrence. Interestingly, the patient carried germline variants which might have predisposed him to carcinogenesis, together with a history of alcohol and tobacco consumption. Mutational signature analysis confirmed the impact of alcohol exposure, with Signature 16 present in all tumour samples. Characterisation of immune cell infiltration highlighted an immunosuppressive environment in all samples, which exceeded the potential activity of T cells. Studies such as the one described here have important clinical value and contribute to personalised treatment decisions for patients with synchronous primaries and matched recurrences.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-01T14:18:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004858","title":"HCA_LNG_Foetal_MRC_spatial","description":"Interrogation of human foetal lung using spatial transcriptomics","abstract":"Investigation of foetal lung throughout development.  We have generated single cell RNA sequencing data from first and second trimester foetal lungs and wish to validate a number of cell populations, particularly alveolar bud tip cells, throughout development using spatial transcriptomics.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004859","title":"HCA_Gut_Foetal_WSSS_spatial","description":"Interrogation of human gut development using spatial transcriptomics","abstract":"The intestinal villi- crypt structures are essential units that increase the epithelial surface area and enable efficient nutrient absorption in adults. Villi formation begins during first trimester of development and involves a step-wise process dependent on the signaling from stromal cell populations, including mesenchyme and smooth muscle. We have used single cell RNA sequencing to profile multiple regions from the first and second trimester tissues of the human gut and identified a number of immune cell populations that have not been reported in fetal gut before. In adults, T cells have been previously shown to affect epithelial differentiation (Biton et al, 2018). We hypothesize that villi formation is dependent on signaling from surrounding immune populations. In this study, we will apply spatial methods such as 10X Visium and whole-mount RNAscope to interrogate the role of immune cells in shaping development of intestinal epithelium in humans.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004860","title":"PBMC gene expression profiles in diet treated celiac disease upon oral gluten challenge","description":null,"abstract":"We aimed to study the molecular impact of short gluten exposure in GFD treated CD patients, as well as identify biological pathways that remain altered in CD regardless of treatment. We used STRT/C1 (single-cell tagged reverse transcription), a 5’-end RNA sequencing method, suitable for quick and cost-efficient gene expression profiling with very low starting RNA, to profile PBMC samples collected from treated CD patients, and gluten challenged patients and healthy controls. Short gluten exposure of just three days was enough to alter the genome-wide PBMC transcriptome of patients. Pathway analysis revealed gluten-induced upregulation of mainly immune response related pathways, both innate and adaptive, in CD patients. We evaluated the perturbation of biological pathways in sample-specific manner. Compared to gluten exposed healthy controls, pathways related to tight junction, olfactory transduction, metabolism of unsaturated fatty acids (such as arachidonic acid), metabolism of amino acids (such as cysteine and glutamate), and microbial infection were constitutively altered in CD patients regardless of treatment, while GFD treatment appears to mostly normalize immune response pathways to “healthy” state. Upstream regulator prediction analysis using differentially expressed genes identified constitutively activated regulators relatively proximal to previously reported CD associated loci, particularly SMARCA4 on 19p13.2 and CSF2 on 5q31. We also found constitutively upregulated genes in CD that are in CD associated genetic loci such as MEF2BNB-MEF2B (BORCS8-MEF2B) on 19p13.11 and CSTB on 21q22.3. RNAseq revealed strong effects of short oral gluten challenge on whole PBMC fraction and constitutively altered pathways in CD PBMC suggesting important factors other than gluten in CD pathogenesis.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-01T19:42:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004861","title":"Bulk-RNA Sequencing of high-grade pancreatic and non-pancreatic Neuroendocrine Neoplasms","description":"Therapeutic decisions in oncology depend on a precise pathological classification of individual neoplasms. Recent years have seen an intensification of research activities aimed at the extraction of clinically relevant information from patient-derived 'omics' data based on Machine-Learning models. However, a comprehensive training of Machine-Learning models requires sufficiently large numbers of training samples, which are usually not available for rare cancer types. The problem is worsened when individual tissues segregate into different cancer subtypes, as their discrimination would require even more training samples.\nMethods:\nHere, we report on a new data-augmentation technique to support the training of Machine-Learning models on ‘omics’ data from pancreatic neuroendocrine neoplasms (panNEN). PanNENs display all properties described above: Only about 2-3% of all pancreatic neoplasms are neuroendocrine and they fall into different subtypes with distinctly different prognosis, which makes the precise classification of such samples both difficult and important for therapy decisions. The approach reconstructs a given transcriptome based on healthy pancreatic cell type signatures and creates a Machine-Learning model that integrates the observed reconstruction error and predicted cell type proportions as features. \nResults:\nA benchmark of the deconvolution model predictions with the ground-truth found that the model could efficiently predict the sample grading, disease-related patient survival time, and differentiate between different subtypes in four panNEN and one mixed panNEN and non-pancreatic NENs dataset. We compared the predictive performance of the deconvolution-trained model to that of a model trained directly on the transcriptomic data, under inclusion of the Ki-67 classification gold standard biomarker, and found the performances to be comparable.\nConclusion:\nOur approach serves as a data-augmentation technique to facilitate  the training of Machine Learning  models for rare cancer types via utilization of data from healthy origin. Additionally, the deconvolution results were clinically interpretable and further research can render the deconvolution approach an effective complementary asset for the clinical classification of neoplasms.","abstract":"Therapeutic decisions in oncology depend on a precise pathological classification of individual neoplasms. Recent years have seen an intensification of research activities aimed at the extraction of clinically relevant information from patient-derived 'omics' data based on Machine-Learning models. However, a comprehensive training of Machine-Learning models requires sufficiently large numbers of training samples, which are usually not available for rare cancer types. The problem is worsened when individual tissues segregate into different cancer subtypes, as their discrimination would require even more training samples.\nMethods:\nHere, we report on a new data-augmentation technique to support the training of Machine-Learning models on ‘omics’ data from pancreatic neuroendocrine neoplasms (panNEN). PanNENs display all properties described above: Only about 2-3% of all pancreatic neoplasms are neuroendocrine and they fall into different subtypes with distinctly different prognosis, which makes the precise classification of such samples both difficult and important for therapy decisions. The approach reconstructs a given transcriptome based on healthy pancreatic cell type signatures and creates a Machine-Learning model that integrates the observed reconstruction error and predicted cell type proportions as features. \nResults:\nA benchmark of the deconvolution model predictions with the ground-truth found that the model could efficiently predict the sample grading, disease-related patient survival time, and differentiate between different subtypes in four panNEN and one mixed panNEN and non-pancreatic NENs dataset. We compared the predictive performance of the deconvolution-trained model to that of a model trained directly on the transcriptomic data, under inclusion of the Ki-67 classification gold standard biomarker, and found the performances to be comparable.\nConclusion:\nOur approach serves as a data-augmentation technique to facilitate  the training of Machine Learning  models for rare cancer types via utilization of data from healthy origin. Additionally, the deconvolution results were clinically interpretable and further research can render the deconvolution approach an effective complementary asset for the clinical classification of neoplasms.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-02T09:01:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004862","title":"UROMOL 2020 - SNP data","description":"The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we performed a large integrative multi-omics analysis of patients diagnosed with NMIBC (n=834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters.","abstract":"The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we performed a large integrative multi-omics analysis of patients diagnosed with NMIBC (n=834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-02T15:23:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004863","title":"DEREGULATION OF PRE-mRNA SPLICING IN MISMATCH REPAIR DEFICIENT COLORECTAL CANCER","description":null,"abstract":"Here we performed whole exome sequencing on a series of 42 Microsatellite (MSI) colorectal cancers (CRC) &amp; 133 RNA sequencing  of \n101 MSI CRC and 32 Microsatellite Stable (MSS) CRC","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-02T15:51:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004864","title":"Genomic analysis of a hypermutated gliosarcoma","description":"Gliosarcoma is a variant of glioblastoma with equally poor prognosis and characterized by mixed glial and mesenchymal pathology. Metastasis is not uncommon but involvement of the spinal cord is rare, and comprehensive genetic characterization of spinal gliosarcoma is lacking. We describe a patient initially diagnosed with a low-grade brain glioma via biopsy, followed by adjuvant radiation and temozolomide treatment. Nearly two years after diagnosis, she developed neurological deficits from an intradural, extramedullary tumor anterior to the spinal cord at T4, which was resected and diagnosed as gliosarcoma. Whole-exome sequencing (WES) of this tumor revealed a hypermutated phenotype, characterized by somatic mutations in key DNA mismatch repair (MMR) pathway genes, an abundance of C&gt;T transitions within the identified somatic SNVs, and microsatellite stability, together consistent with temozolomide-mediated hypermutagenesis. This is the first report of a hypermutator phenotype in gliosarcoma, which may represent a novel genomic mechanism of progression from lower-grade glioma.","abstract":"Gliosarcoma is a variant of glioblastoma with equally poor prognosis and characterized by mixed glial and mesenchymal pathology. Metastasis is not uncommon but involvement of the spinal cord is rare, and comprehensive genetic characterization of spinal gliosarcoma is lacking. We describe a patient initially diagnosed with a low-grade brain glioma via biopsy, followed by adjuvant radiation and temozolomide treatment. Nearly two years after diagnosis, she developed neurological deficits from an intradural, extramedullary tumor anterior to the spinal cord at T4, which was resected and diagnosed as gliosarcoma. Whole-exome sequencing (WES) of this tumor revealed a hypermutated phenotype, characterized by somatic mutations in key DNA mismatch repair (MMR) pathway genes, an abundance of C&gt;T transitions within the identified somatic SNVs, and microsatellite stability, together consistent with temozolomide-mediated hypermutagenesis. This is the first report of a hypermutator phenotype in gliosarcoma, which may represent a novel genomic mechanism of progression from lower-grade glioma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-02T18:15:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004865","title":"WGS Leiomyosarcoma subtypes","description":null,"abstract":"Leiomyosarcomas (LMS) are genetically heterogeneous tumors differentiating along smooth muscle lines. Currently, LMS treatment is not informed by molecular subtyping and is associated with highly variable survival. While disease site continues to dictate clinical management, the contribution of genetic factors to LMS subtype, origins, and timing are unknown. Here we analyzed 70 genomes and 130 transcriptomes of LMS, including multiple tumor regions and paired metastases. Molecular profiling highlighted the extremely early origins of LMS. Three specific subtypes of LMS develop from distinct lineages of smooth muscle cells. Of these, dedifferentiated LMS with high immune infiltration and tumors primarily of gynaecological origin acquired the highest burden of genomic mutation and are associated with worse survival. Homologous recombination defects lead to genome-wide mutational signatures, and a corresponding sensitivity to PARP and other DNA damage response inhibitors, suggesting a novel  therapeutic    strategy for LMS. Finally, by phylogenetic reconstruction, we present evidence that clones seeding lethal metastases arise decades prior to LMS diagnosis.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004866","title":"Gut metagenome for population cohort","description":null,"abstract":"The main goal of the project is the study the associations between the gut metagenome and human health. The dataset contains data for n=7211 FINRISK 2002 participants who underwent feral sampling. Demultiplexed shallow shotgun metagenomic sequences were quality filtered and adapter trimmed using Atropos (Didion et al., 2017), and human filtered using Bowtie2 (Langmead and Salzberg, 2012).","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004867","title":"Targeted de-methylation of the FOXP3-TSDR","description":"CD4+ regulatory T cells (Tregs) are key mediators of immunological tolerance and promising effector cells for immuno-suppressive adoptive cellular therapy to fight autoimmunity and chronic inflammation. Their functional stability is critical for their clinical utility and has been correlated to the demethylated state of the TSDR/CNS2 enhancer element in the Treg lineage transcription factor FOXP3. However, proof for a causal contribution of the TSDR de-methylation to FOXP3 stability and Treg induction is so far lacking. We here established a powerful transient-transfection CRISPR-Cas9-based epigenetic-editing method for the selective de-methylation of the TSDR within the endogenous chromatin environment of a living cell. The induced de-methylated state was stable over weeks in clonal T cell proliferation cultures even after expression of the editing complex had ceased. Epigenetic editing of the TSDR resulted in FOXP3 expression, even in its physiological isoform distribution, proving a causal role for the de-methylated TSDR in FOXP3 regulation. However, successful FOXP3 induction was not associated with a switch towards a functional Treg phenotype, in contrast to what has been reported from FOXP3 overexpression approaches. Thus, TSDR de-methylation is required, but not sufficient for a stable Treg phenotype induction. Therefore, targeted demethylation of the TSDR may be a critical addition to published in vitro Treg induction protocols which so far lack FOXP3 stability.","abstract":"CD4+ regulatory T cells (Tregs) are key mediators of immunological tolerance and promising effector cells for immuno-suppressive adoptive cellular therapy to fight autoimmunity and chronic inflammation. Their functional stability is critical for their clinical utility and has been correlated to the demethylated state of the TSDR/CNS2 enhancer element in the Treg lineage transcription factor FOXP3. However, proof for a causal contribution of the TSDR de-methylation to FOXP3 stability and Treg induction is so far lacking. We here established a powerful transient-transfection CRISPR-Cas9-based epigenetic-editing method for the selective de-methylation of the TSDR within the endogenous chromatin environment of a living cell. The induced de-methylated state was stable over weeks in clonal T cell proliferation cultures even after expression of the editing complex had ceased. Epigenetic editing of the TSDR resulted in FOXP3 expression, even in its physiological isoform distribution, proving a causal role for the de-methylated TSDR in FOXP3 regulation. However, successful FOXP3 induction was not associated with a switch towards a functional Treg phenotype, in contrast to what has been reported from FOXP3 overexpression approaches. Thus, TSDR de-methylation is required, but not sufficient for a stable Treg phenotype induction. Therefore, targeted demethylation of the TSDR may be a critical addition to published in vitro Treg induction protocols which so far lack FOXP3 stability.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-03T09:45:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004868","title":"Genetic makeup of agnospheres","description":"Agnospheres are cultures of cancer stem cells isolated from tissue biopsies from patients with Cancer of Unknown Primary (CUPs). The latter is a lethal malignancy (median survival &lt;1 year), representing approximately the 3% of all cancers, and characterized by metastatic dissemination in the absence of a primary tumor recognizable by a standardized protocol including thorough body imaging and histopathological analysis.\nAgnospheres are long-term propagated in culture and, after subcutaneous injection into immunocompromised mice, they display high tumorigenicity and quickly reproduce the clinical presentation of the original tumor, featuring a multi-organ metastatic pattern and poorly differentiated histology.\nThe goal of the project is to analyse the mutational profile of agnospheres in detail, as to verify its correspondance with that of the original tumors. Genetic information will be exploited to investigate the genetic drivers of the CUP phenotype, in particular the hypermetastatic ability and the differentiative block.","abstract":"Agnospheres are cultures of cancer stem cells isolated from tissue biopsies from patients with Cancer of Unknown Primary (CUPs). The latter is a lethal malignancy (median survival &lt;1 year), representing approximately the 3% of all cancers, and characterized by metastatic dissemination in the absence of a primary tumor recognizable by a standardized protocol including thorough body imaging and histopathological analysis.\nAgnospheres are long-term propagated in culture and, after subcutaneous injection into immunocompromised mice, they display high tumorigenicity and quickly reproduce the clinical presentation of the original tumor, featuring a multi-organ metastatic pattern and poorly differentiated histology.\nThe goal of the project is to analyse the mutational profile of agnospheres in detail, as to verify its correspondance with that of the original tumors. Genetic information will be exploited to investigate the genetic drivers of the CUP phenotype, in particular the hypermetastatic ability and the differentiative block.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-03T10:41:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004869","title":"POPCOL: population-based colonoscopy.","description":"PopCol is a cohort study in Stockholm, Sweden that includes a data-rich set of individuals with data available from bowel symptoms questionnaires, gastroenterology visits and biospecimens (genotype and 16S sequencing from blood and stool samples, respectively). Genotyping was carried out using the Illumina HumanOmniExpressExome-8v1 arrays at the SciLifeLab NGI facility in Uppsala, Sweden. Fecal DNA was extracted from samples kept at -80°C using Qiagen 5 QIAamp DNA Stool Mini Kits and analyzed using 16S rRNA gene amplicon sequencing (in the V1-V2 hypervariable region). This was performed on the Illumina MiSeq platform at the Institute of Clinical Molecular Biology (IKMB) in Kiel, Germany. Of these, six PopCol participants were PPI users and 12 used antibiotics. The study was approved by the local Committee of Research Ethics (Forskningskommitté Syd) at Karolinska Institutet, Stockholm, in November 2001. Written informed consent was obtained from all participants","abstract":"PopCol is a cohort study in Stockholm, Sweden that includes a data-rich set of individuals with data available from bowel symptoms questionnaires, gastroenterology visits and biospecimens (genotype and 16S sequencing from blood and stool samples, respectively). Genotyping was carried out using the Illumina HumanOmniExpressExome-8v1 arrays at the SciLifeLab NGI facility in Uppsala, Sweden. Fecal DNA was extracted from samples kept at -80°C using Qiagen 5 QIAamp DNA Stool Mini Kits and analyzed using 16S rRNA gene amplicon sequencing (in the V1-V2 hypervariable region). This was performed on the Illumina MiSeq platform at the Institute of Clinical Molecular Biology (IKMB) in Kiel, Germany. Of these, six PopCol participants were PPI users and 12 used antibiotics. The study was approved by the local Committee of Research Ethics (Forskningskommitté Syd) at Karolinska Institutet, Stockholm, in November 2001. Written informed consent was obtained from all participants","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-03T10:54:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004870","title":"NIHR BioResource Common Disease Patients 2016","description":"NIHR BioResource Common Disease Patients 2016. The dataset includes 13489 samples from blood donors, they were not screened for any particular disease, and therefore they are representative of the general population. Genomic data includes 845487 snps  collected using the UK BioBank V1 Affymetrix array. Phenotypic data includes gender, age, ethnicity and disease.\nAccording to our internal quality check there are 81 duplicates in this dataset.","abstract":"NIHR BioResource Common Disease Patients 2016. The dataset includes 13489 samples from blood donors, they were not screened for any particular disease, and therefore they are representative of the general population. Genomic data includes 845487 snps  collected using the UK BioBank V1 Affymetrix array. Phenotypic data includes gender, age, ethnicity and disease.\nAccording to our internal quality check there are 81 duplicates in this dataset.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-03T12:33:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004871","title":"Single-cell multi-omic profiling of glioblastoma-associated myeloid cells","description":null,"abstract":"Glioblastomas are aggressive primary brain cancers that invariably recur as therapy-resistant tumors. Myeloid cells control glioblastoma malignancy, but their dynamics during disease progression remains poorly understood. By relying on single-cell RNA and protein profiling, we mapped the glioblastoma immune landscape in newly diagnosed and recurrent patients. This revealed a large and diverse myeloid compartment, with dendritic cell and macrophage populations that were dynamic across disease stages.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-03T12:49:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004872","title":"Biological and Therapeutic Implications of a Unique Subtype of NPM1 Mutated AML","description":null,"abstract":"In acute myeloid leukemia (AML), molecular heterogeneity across patients constitutes a major challenge for prognosis and therapy. AML with NPM1 mutation is a distinct genetic entity in the revised World Health Organization classification. However, differing patterns of co-mutation and response to therapy within this group necessitate further stratification. Here we report two distinct subtypes within NPM1 mutated AML patients, which we label as primitive and committed based on the respective presence or absence of a stem cell signature. Using gene expression (RNA-seq), epigenomic (ATAC-seq) and immunophenotyping (CyToF) analysis, we were able to associate each subtype with specific molecular characteristics, disease differentiation state and patient survival. Using ex vivo drug sensitivity profiling, we show a differential drug response of the subtypes to specific kinase inhibitors, irrespective of the FLT3-ITD status. Differential drug responses of the primitive and committed subtype were validated in an independent AML cohort. Our results highlight heterogeneity among NPM1 mutated AML patient samples based on stemness and suggest that the addition of kinase inhibitors to the treatment of cases with the primitive signature, lacking FLT3-ITD, could have therapeutic benefit.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-03T13:36:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004873","title":"MutWP4__CRUK_Grand_Challenge_Mutographs_of_Cancer__Mutagen_treated_organoids","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, Kings College London will characterise the mutational signatures induced by putative human carcinogens in order to identify the origins of mutational signatures found in human cancers. To achieve this human organoid cell cultures will be exposed to a representative catalogue of known or suspected human carcinogens and mutagens and, using whole genome sequencing, the patterns of mutations induced by them will be determined. Somatic mutational signatures will be subsequently extracted by non-negative matrix factorisation methods and correlated with exposure data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"he Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, Kings College London will characterise the mutational signatures induced by putative human carcinogens in order to identify the origins of mutational signatures found in human cancers. To achieve this human organoid cell cultures will be exposed to a representative catalogue of known or suspected human carcinogens and mutagens and, using whole genome sequencing, the patterns of mutations induced by them will be determined. Somatic mutational signatures will be subsequently extracted by non-negative matrix factorisation methods and correlated with exposure data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-03T13:37:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004874","title":"Test 1","description":null,"abstract":"Sleep is associated with various health outcomes. Despite their growing adoption, the potential for consumer wearables to contribute sleep metrics to sleep-related biomedical research remains largely uncharacterized. Here we analyzed sleep tracking data, along with questionnaire responses and multi-modal phenotypic data generated from 482 normal volunteers. First, we compared wearable-derived and self-reported sleep metrics, particularly total sleep time (TST) and sleep efficiency (SE). We then identified demographic, socioeconomic and lifestyle factors associated with wearable-derived TST. Among others, male gender (β = -15.539, 95% confidence interval [CI] = -26.245 - -4.832, p = 0.005), older age (β = -0.493, CI = -0.941 - -0.044, p = 0.032) and manual labor (β = -26.856, CI = -49.715 - -3.997, p = 0.022) were associated with reduced TST, whereas alcohol consumption (β = 19.247, CI = 8.008 - 30.486, p = 8.54x10-04) was associated with increased TST. Multi-modal phenotypic data analysis showed that wearable-derived TST and SE were associated with various cardiovascular disease risk markers such as body mass index (β = -0.006, CI = -0.00 - -0.000, p = 0.040) and waist circumference (β = 0.001, CI = -0.015-0.017, p = 0.893), whereas self-reported measures were not. We then showed that insufficient sleep was associated with premature telomere attrition, using telomere length estimated using whole-genome sequencing (β = 1.275, CI = 0.187 - 2.363, p = 0.023) and quantitative PCR (β = 0.001, CI = 8.318x10-05 - 0.001, p = 0.028). Our study highlights the potential for sleep metrics from consumer wearables to provide novel insights into data generated from population cohort studies.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004875","title":"ChIP Sequencing of G34RV mutant paediatric high grade gliomas","description":"Oncohistone mutations in H3-3A/H3F3A represent signature genetic events of high-grade gliomas (HGGs) in children and young adults, which account for the major cause of cancer-related deaths in this age group with a median overall survival of 9-15 months.  Among these tumors, mutually exclusive missense mutations at either lysine 27 (K27M) or glycine 34 (G34R/V) in the tail of histone 3.3 define two clinical-molecular groups, which segregate by location and age of incidence, suggesting distinct neurodevelopmental contexts of originH3 G34R/V gliomas are genomically distinct from their H3 K27M-mutant and histone-wildtype counterparts. Notably, the H3.3 G34R/V mutation is found in a histologically heterogeneous group of brain tumors that comprise glioblastomas, but also neoplasms formerly defined as primitive neuroectodermal tumors (CNS-PNETs).To more extensively characterize the pathophysiological basis and to derive targetable strategies against  H3.3 G34R/V mutant paediatric gliomas, we here combine ChIP sequencing, bulk RNA sequencing, single-cell sequencing approaches and genome-wide CRISPR-screening in  patient-derived H3 G34R/V tumor cells. Our integrative analysis reveals both vulnerabilities associated with a putative GABAergic interneuronal progenitor lineage and clinically actionable targets, as validated using functional approaches.","abstract":"Oncohistone mutations in H3-3A/H3F3A represent signature genetic events of high-grade gliomas (HGGs) in children and young adults, which account for the major cause of cancer-related deaths in this age group with a median overall survival of 9-15 months.  Among these tumors, mutually exclusive missense mutations at either lysine 27 (K27M) or glycine 34 (G34R/V) in the tail of histone 3.3 define two clinical-molecular groups, which segregate by location and age of incidence, suggesting distinct neurodevelopmental contexts of originH3 G34R/V gliomas are genomically distinct from their H3 K27M-mutant and histone-wildtype counterparts. Notably, the H3.3 G34R/V mutation is found in a histologically heterogeneous group of brain tumors that comprise glioblastomas, but also neoplasms formerly defined as primitive neuroectodermal tumors (CNS-PNETs).To more extensively characterize the pathophysiological basis and to derive targetable strategies against  H3.3 G34R/V mutant paediatric gliomas, we here combine ChIP sequencing, bulk RNA sequencing, single-cell sequencing approaches and genome-wide CRISPR-screening in  patient-derived H3 G34R/V tumor cells. Our integrative analysis reveals both vulnerabilities associated with a putative GABAergic interneuronal progenitor lineage and clinically actionable targets, as validated using functional approaches.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004876","title":"Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts-BRCA-EurOPDX Institut Curie","description":null,"abstract":"Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical\nstudies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution\nduring PDX engraftment and propagation, impacting the accuracy of PDX modeling of human\ncancer. Here we exhaustively analyze copy number alterations (CNAs) in 1451 PDX and matched\npatient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing\nand microarray data displayed substantially higher resolution and dynamic range than gene\nexpression-based inferences, and they also showed strong CNA conservation from PTs through\nlate-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-\nlate trios confirmed high-resolution CNA retention. We observed no significant enrichment of\ncancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between\npatient and PDX tumors were comparable to variations in multi-region samples within patients.\nOur study demonstrates the lack of systematic copy number evolution driven by the PDX mouse\nhost.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004877","title":"Accurate detection of tumor-specific fusion genes reveals strongly immunogenic personal neo-antigens","description":"Fusion genes arising from cancer-associated somatic mutations are a potential rich source for highly immunogenic neo-antigens. However, their exploitation as targets for personalized cancer immunotherapy is currently limited by the lack of computational tools allowing transcriptome-wide identification of unique fusion genes in an accurate and sensitive manner. Here, we present EasyFuse, a computational pipeline, to detect individual and cancer-specific fusion genes in next-generation-sequencing transcriptome data obtained from human cancer samples. Using machine learning, EasyFuse predicts personal fusion genes with high precision and sensitivity and outperforms previously described approaches as qualified by an unprecedented ground-truth dataset of &gt;1500 verification experiments in relevant patient samples. By testing immunogenicity with autologous blood lymphocytes from cancer patients we detected pre-established CD4+ and CD8+ T cell responses for 10 of 21 (48%), and for 1 of 30 (3%) of identified fusion genes, respectively. In conclusion, we demonstrate accurate detection of cancer-specific fusion genes. The high frequency of T cell responses detected in cancer patients support the relevance of private fusion genes as neo-antigens for personalized immunotherapies, especially for tumors with low point mutation burdens.","abstract":"Fusion genes arising from cancer-associated somatic mutations are a potential rich source for highly immunogenic neo-antigens. However, their exploitation as targets for personalized cancer immunotherapy is currently limited by the lack of computational tools allowing transcriptome-wide identification of unique fusion genes in an accurate and sensitive manner. Here, we present EasyFuse, a computational pipeline, to detect individual and cancer-specific fusion genes in next-generation-sequencing transcriptome data obtained from human cancer samples. Using machine learning, EasyFuse predicts personal fusion genes with high precision and sensitivity and outperforms previously described approaches as qualified by an unprecedented ground-truth dataset of &gt;1500 verification experiments in relevant patient samples. By testing immunogenicity with autologous blood lymphocytes from cancer patients we detected pre-established CD4+ and CD8+ T cell responses for 10 of 21 (48%), and for 1 of 30 (3%) of identified fusion genes, respectively. In conclusion, we demonstrate accurate detection of cancer-specific fusion genes. The high frequency of T cell responses detected in cancer patients support the relevance of private fusion genes as neo-antigens for personalized immunotherapies, especially for tumors with low point mutation burdens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-07T12:54:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004878","title":"Pancreatic, Small-intestinal and Pulmonary Neuroendocrine Tumors","description":"Purpose: The primary origin of neuroendocrine tumor metastases can be difficult to determine by histopathology alone, but is critical for therapeutic decision making. DNA methylation-based profiling is now routinely used in the diagnostic workup of brain tumors. This has been enabled by the availability of cost-efficient array-based platforms. We have extended these efforts to augment histopathological diagnosis in neuroendocrine tumors. \nExperimental Design and Results: We compiled data of 69 small-intestinal, pulmonary, and pancreatic neuroendocrine tumors. These data were used to build a ridge regression calibrated random forest classification algorithm (NEN-ID) that predicts the origin of tumor samples with high accuracy (&amp;gt; 95%). The model was validated during 3x3 nested cross validation and tested in a local (n=26) and external (n=172) cohort. In addition, we show that our diagnostic approach is robust across a range of possible confounding experimental parameters such as tumor purity and array quality. A software infrastructure and online user interface was built to make the model available to the scientific community.\nConclusions: This DNA methylation-based prediction model can be used in the workup for patients with neuroendocrine tumors of unknown primary. To facilitate validation and clinical implementation, we provide a user-friendly, publicly available web-based version of NEN-ID.","abstract":"Purpose: The primary origin of neuroendocrine tumor metastases can be difficult to determine by histopathology alone, but is critical for therapeutic decision making. DNA methylation-based profiling is now routinely used in the diagnostic workup of brain tumors. This has been enabled by the availability of cost-efficient array-based platforms. We have extended these efforts to augment histopathological diagnosis in neuroendocrine tumors. \nExperimental Design and Results: We compiled data of 69 small-intestinal, pulmonary, and pancreatic neuroendocrine tumors. These data were used to build a ridge regression calibrated random forest classification algorithm (NEN-ID) that predicts the origin of tumor samples with high accuracy (&amp;gt; 95%). The model was validated during 3x3 nested cross validation and tested in a local (n=26) and external (n=172) cohort. In addition, we show that our diagnostic approach is robust across a range of possible confounding experimental parameters such as tumor purity and array quality. A software infrastructure and online user interface was built to make the model available to the scientific community.\nConclusions: This DNA methylation-based prediction model can be used in the workup for patients with neuroendocrine tumors of unknown primary. To facilitate validation and clinical implementation, we provide a user-friendly, publicly available web-based version of NEN-ID.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-08T08:37:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004879","title":"Targeted Sequencing of Shwachman-Diamond syndrome bone marrow samples","description":null,"abstract":"Targeted sequencing of myeloid malignancy-associated genes as well as EIF6 in bone marrow samples in Shwachman-Diamond syndrome patients. Paired bone marrow fibroblasts serve as a germline control.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-08T14:10:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004880","title":"Whole Exome sequencing data from Shwachman-Diamond syndrome bone marrow samples","description":null,"abstract":"To define the mechanistic basis of clonal hematopoiesis in Shwachman-Diamond syndrome (SDS), we investigated somatic mutations acquired by patients with SDS followed longitudinally.  This dataset includes the initial discovery cohort whole exome sequencing from bone marrow samples used to identify novel somatic mutations in patients with SDS.  Paired fibroblasts serve as a germline control.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-08T14:14:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004881","title":"Single cell sequencing data from Shwachman-Diamond syndrome bone marrow","description":null,"abstract":"To define the mechanistic basis of clonal hematopoiesis in SDS, we investigated somatic\nmutations acquired by patients with SDS followed longitudinally.  This dataset includes single cell sequencing data from SDS bone marrow as well as serial samples from a single patient that went on to develop AML.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-08T14:16:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004882","title":"Somatic_evolution_in_the_psoriatic_skin","description":"We will use laser capture microdissection to dissect groups of a few hundred cells, from which we will isolate and sequence nucleic acids. We aim to whole-genome, whole-exome and RNA sequence the samples in effort to understand the accumulation of somatic mutations in psoriasis and their effect on transcription.","abstract":"We will use laser capture microdissection to dissect groups of a few hundred cells, from which we will isolate and sequence nucleic acids. We aim to whole-genome, whole-exome and RNA sequence the samples in effort to understand the accumulation of somatic mutations in psoriasis and their effect on transcription.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-09T08:51:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004883","title":"HCA_Brain_Disease_ALS_Bayraktar_RNA_KE_c9ALS","description":"Single-nucleus sequencing of ALS and control adult brain samples","abstract":"In this study, we apply single-nucleus sequencing to ALS and control adult brain samples from multiple cortical brain regions. We aim to understand how, and which, specific cell types, are affected in the known pathophysiological regions in ALS, as well as elucidate commonalities and trends between patients with disparate underlying genetic causes and phenotypic manifestations. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004884","title":"Molecular evolution and clinical trajectories of prostate cancer identifies novel markers for risk stratification - additional data","description":null,"abstract":"Prostate cancer is a highly heterogeneous disease that is thought to develop over many years. Identifying the earliest somatic changes can give important insights into the tumour evolution and aid in stratifying high- from low-risk diseases. Here we pursued integrative whole-genome, transcriptome and methylome-based analysis of early-onset prostate cancer patients. Characterisation of genomic alterations across 270 PCa tumours revealed age-related genomic alterations and mutation signatures including BRCAness and APOBEC. We used methylation- and expression-data to identify four molecular subgroups, which included a highly aggressive tumour subgroup that frequently involved recurrent duplications and increased expression of ESRP1. Analysis of 12,000 tissue-microarray tumour samples demonstrated that ESRP1 is a candidate biomarker associated with faster proliferation rate and shorter time to relapse. We combine the patterns of molecular co-occurrence, risk-stratification and subgroup information to deconvolute tumor heterogeneity, which reveal complex but recurrent clinical trajectories of prostate cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-09T16:47:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004885","title":"Gut microbiome sequencing in patients receiving combination immune checkpoint blockade","description":"This dataset contains 16S and WMS data for gut (fecal) microbiome samples taken from patients treated with combined anti-CTLA-4 and anti-PD-1 checkpoint blockade for advanced melanoma.","abstract":"This dataset contains 16S and WMS data for gut (fecal) microbiome samples taken from patients treated with combined anti-CTLA-4 and anti-PD-1 checkpoint blockade for advanced melanoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-10T04:35:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004886","title":"mRNA and T cell receptor sequencing of patients with Pandemrix-associated narcolepsy type 1","description":"Increased risk of Narcolepsy type 1 (NT1) was reported among children and adolescents vaccinated with AS03-adjuvanted pandemic influenza A vaccine (H1N1; Pandemrix®). We hypothesized that viral T cell epitope(s) in Pandemrix mimicked self-epitope(s), and that recognition of these cross-reactive epitopes contributed to disease-specific autoimmunity. We demonstrate that pediatric, Pandemrix-associated NT1 patients had enhanced T-cell immunity against dominant T-cell epitopes of Pandemrix vaccine viral proteins neuraminidase (NA) and nucleoprotein (NP), and also responded against a self-epitope in brain-expressed protein-O-mannosyltransferase 1 (POMT1). Here, the gene expression profiles and TCR repertoire of PBMC from patients and healthy controls were compared. PBMC samples were stimulated with peptides NA-175-189 or POMT1-675-589, and bulk RNA isolated and sequenced (RNAseq and TCRseq).","abstract":"Increased risk of Narcolepsy type 1 (NT1) was reported among children and adolescents vaccinated with AS03-adjuvanted pandemic influenza A vaccine (H1N1; Pandemrix®). We hypothesized that viral T cell epitope(s) in Pandemrix mimicked self-epitope(s), and that recognition of these cross-reactive epitopes contributed to disease-specific autoimmunity. We demonstrate that pediatric, Pandemrix-associated NT1 patients had enhanced T-cell immunity against dominant T-cell epitopes of Pandemrix vaccine viral proteins neuraminidase (NA) and nucleoprotein (NP), and also responded against a self-epitope in brain-expressed protein-O-mannosyltransferase 1 (POMT1). Here, the gene expression profiles and TCR repertoire of PBMC from patients and healthy controls were compared. PBMC samples were stimulated with peptides NA-175-189 or POMT1-675-589, and bulk RNA isolated and sequenced (RNAseq and TCRseq).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-10T11:48:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004887","title":"EAC Genomic data","description":null,"abstract":"Our objective was to identify molecular features and develop a prognostic model by profiling the genomic features of mEGAC patients with widely varying outcomes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-10T15:44:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004888","title":"Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities","description":"Despite molecular and clinical heterogeneity, small cell lung cancer (SCLC) is treated as a single entity with predictably poor results. Using tumor expression data, we applied non-negative matrix factorization, which identified four SCLC subtypes defined largely by differential expression of transcription factors ASCL1, NEUROD1, and POU2F3 or low expression of all three transcription factor signatures accompanied by an Inflamed signature (SCLC-A, N, P and I, respectively). The presence of these subtypes were then validated in tumor gene expression data from the IMpower133 clinical trial.","abstract":"Despite molecular and clinical heterogeneity, small cell lung cancer (SCLC) is treated as a single entity with predictably poor results. Using tumor expression data, we applied non-negative matrix factorization, which identified four SCLC subtypes defined largely by differential expression of transcription factors ASCL1, NEUROD1, and POU2F3 or low expression of all three transcription factor signatures accompanied by an Inflamed signature (SCLC-A, N, P and I, respectively). The presence of these subtypes were then validated in tumor gene expression data from the IMpower133 clinical trial.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-10T18:40:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004889","title":"Multi-omics profiling of PSCCE","description":"We performed whole-exome sequencing, RNA sequencing and immunohistochemistry profiling of primary small cell carcinomas of the esophagus.","abstract":"We performed whole-exome sequencing, RNA sequencing and immunohistochemistry profiling of primary small cell carcinomas of the esophagus.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-11T01:30:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004890","title":"Impact of BRCA mutation type in non-tumorous breast tissue transcriptome","description":"To investigate the transcriptomic difference between BRCA1 vs. BRCA2 carriers, RNA sequencing was carried out.","abstract":"To investigate the transcriptomic difference between BRCA1 vs. BRCA2 carriers, RNA sequencing was carried out.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-11T03:44:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004891","title":"DATA UPLOADED TO DBGAP: phs003338.v1.p1 - Genetic effects on transcriptome profiles in colon epithelium provide functional insights for genetic risk loci","description":"This data is not archived in the EGA, but in the dbGAP under the ID: phs003338.v1.p1\n\nWe profiled gene expression and alternative splicing of non-neoplastic colon from biopsies of 445 healthy individuals. We showed that single nucleotide polymorphisms associated with these profiles are enriched in disease-associated loci, including colorectal cancer and inflammatory bowel disease.","abstract":"This data is not archived in the EGA, but in the dbGAP under the ID: phs003338.v1.p1\n\nWe profiled gene expression and alternative splicing of non-neoplastic colon from biopsies of 445 healthy individuals. We showed that single nucleotide polymorphisms associated with these profiles are enriched in disease-associated loci, including colorectal cancer and inflammatory bowel disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004892","title":"Targeted sequencing DDR genes in cancer stem cells","description":"Colorectal cancer stem cells (CSCs) show heterogeneous levels of constitutive replication stress leading distinct dependence on the replication stress response. The aim of the projects was to find genetic, epigenetic, phenotypic factors associated with the resistance of colorectal CSCs to inhibitors of the ATR/CHK1 pathway, which regulates of the replication stress response. Different pairs of colorectal CSCs sensitive and resistant to ATR or CHK1 inhibitors were analyzed","abstract":"Colorectal cancer stem cells (CSCs) show heterogeneous levels of constitutive replication stress leading distinct dependence on the replication stress response. The aim of the projects was to find genetic, epigenetic, phenotypic factors associated with the resistance of colorectal CSCs to inhibitors of the ATR/CHK1 pathway, which regulates of the replication stress response. Different pairs of colorectal CSCs sensitive and resistant to ATR or CHK1 inhibitors were analyzed","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-11T16:05:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004893","title":"Leukemia stem cell containing fractions","description":"ATAC-seq performed on leukemic stem cell fractions with different engraftment potential. Leukemic cells were sorted out of Acute Myeloid Leukemia patient samples based on CD34/CD38 status. Samples were annotated based on an independent engraftment assay in mice as LSC+ (engrafting) and LSC- (not engrafting). Omni-ATAC-seq was carried out to compute differential enrichment of transposable elements in chromatin accessible regions.","abstract":"ATAC-seq performed on leukemic stem cell fractions with different engraftment potential. Leukemic cells were sorted out of Acute Myeloid Leukemia patient samples based on CD34/CD38 status. Samples were annotated based on an independent engraftment assay in mice as LSC+ (engrafting) and LSC- (not engrafting). Omni-ATAC-seq was carried out to compute differential enrichment of transposable elements in chromatin accessible regions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-11T20:02:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004894","title":"Single cell T cell Landscape and T Cell Receptor Repertoire Profiling of AML in Context of PD-1 Blockade Therapy","description":"Eight pretreatment and 14 posttreatment bone marrow (BM) aspirates from 8 patients with R/R AML treated with azacitidine and nivolumab along with 2 control BM from healthy donors were profiled with scRNA sequencing with matching scTCR -, scBCR - and scATAC sequencing. Additionally, the targeted DNA sequencing in at least 1 time point per patient (total evaluated 17/22 samples, two samples were performed using CLIA-certified molecular diagnostic assay and data is not available) was performed. The Fastq files and/or bam files are available in this dataset.","abstract":"Eight pretreatment and 14 posttreatment bone marrow (BM) aspirates from 8 patients with R/R AML treated with azacitidine and nivolumab along with 2 control BM from healthy donors were profiled with scRNA sequencing with matching scTCR -, scBCR - and scATAC sequencing. Additionally, the targeted DNA sequencing in at least 1 time point per patient (total evaluated 17/22 samples, two samples were performed using CLIA-certified molecular diagnostic assay and data is not available) was performed. The Fastq files and/or bam files are available in this dataset.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-11T20:56:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004895","title":"Risk and modifying factors in Frontotemporal Dementia","description":"Understanding the molecular mechanisms underlying frontotemporal dementia (FTD) is essential for the development of successful therapies. Here, we present Phase 1 of a multi-omics, multi-model data resource for FTD research which will allows in-depth molecular research into these mechanisms. We have integrated and analysed data from the frontal lobe of FTD patients with mutations in MAPT, GRN and C9orf72 and detected common and distinct dysregulated cellular pathways. Our results highlight that excitatory neurons are the most vulnerable neuronal cell type and that vascular aberrations are a common hallmark in FTD. Via integration of multi-omics data, we detected several transcription factors and pathways which regulate the strong neuroinflammation observed in FTD-GRN. Finally, using small RNA-seq data and verification experiments in cellular models, we identified several up-regulated miRNAs that inhibit cellular trafficking pathways in FTD and lead to microglial activation. In this work we shed light on novel mechanistic and pathophysiological hallmarks of FTD. In addition, we believe that this comprehensive, multi-omics data resource will further mechanistic FTD research by the community.","abstract":"Understanding the molecular mechanisms underlying frontotemporal dementia (FTD) is essential for the development of successful therapies. Here, we present Phase 1 of a multi-omics, multi-model data resource for FTD research which will allows in-depth molecular research into these mechanisms. We have integrated and analysed data from the frontal lobe of FTD patients with mutations in MAPT, GRN and C9orf72 and detected common and distinct dysregulated cellular pathways. Our results highlight that excitatory neurons are the most vulnerable neuronal cell type and that vascular aberrations are a common hallmark in FTD. Via integration of multi-omics data, we detected several transcription factors and pathways which regulate the strong neuroinflammation observed in FTD-GRN. Finally, using small RNA-seq data and verification experiments in cellular models, we identified several up-regulated miRNAs that inhibit cellular trafficking pathways in FTD and lead to microglial activation. In this work we shed light on novel mechanistic and pathophysiological hallmarks of FTD. In addition, we believe that this comprehensive, multi-omics data resource will further mechanistic FTD research by the community.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-12T11:59:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004896","title":"Acute Myeloid Leukemia peripheral blood samples","description":null,"abstract":"Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. Although most patients achieve complete remission after induction chemotherapy, two thirds of patients will relapse within 5 years. The presence of tumour initiating cells positively correlates with tumor progression, recurrence and metastasis 1–6. However, identifying tumour initiating cells and quantifying stemness in bulk tumors remains an ongoing challenge 7–9. Chromatin accessibility reflects cellular identity, lineage 10 and differs between primitive and mature cell states when measured over transposable elements (TE) 11–13. Here we show TE subfamily enrichment within accessible chromatin across the differentiation trajectory of hematopoiesis, and identify the TE subfamilies distinguishing  hematopoietic stem and progenitor cells from mature blood populations. Using leukemia stem cell (LSC) containing fractions, we further show that chromatin accessibility over TE distinguishes LSCs from committed leukemia cells and enriched TE subfamilies in hematopoiesis and AML contribute to cellular phenotype, providing binding sites to crucial transcription factors. We further define a signature (LSCTE121) to score stemness based on chromatin accessibility data from bulk AML samples that stratifies patients prone to relapse, complementing initial risk stratification by the clinical LSC17 score7. Collectively, these results showcase the utility of calculating the enrichment of distinct TE subfamilies within accessible chromatin as a way to distinguish primitive from mature cells, stratify AML patients’ tumor stemness and identify patients prone to relapse.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-12T16:01:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004897","title":"Nuclease deficiencies alter plasma cell-free DNA methylationprofiles (Human)","description":"The effects of DNASE1L3 or DNASE1 deficiency on cfDNA methylation was explored in plasma of mice deficient in these nucleases and in DNASE1L3-deficient humans. Compared to wildtype cfDNA, cfDNA in Dnase1l3-deficient mice was significantly hypomethylated, while cfDNA in Dnase1-deficient mice was hypermethylated. The cfDNA hypomethylation in Dnase1l3-deficient mice was due to increased fragmentation and representation from open chromatin regions (OCRs) and CpG islands (CGIs). These findings were absent in Dnase1-deficient mice.","abstract":"The effects of DNASE1L3 or DNASE1 deficiency on cfDNA methylation was explored in plasma of mice deficient in these nucleases and in DNASE1L3-deficient humans. Compared to wildtype cfDNA, cfDNA in Dnase1l3-deficient mice was significantly hypomethylated, while cfDNA in Dnase1-deficient mice was hypermethylated. The cfDNA hypomethylation in Dnase1l3-deficient mice was due to increased fragmentation and representation from open chromatin regions (OCRs) and CpG islands (CGIs). These findings were absent in Dnase1-deficient mice.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-13T12:26:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004898","title":"Urinary cell-free DNA fragmentation patterns in Dnase1 and Dnase1l3 deficient mice","description":"Urinary cell-free DNA fragmentation patterns in Dnase1 and Dnase1l3 deficient mice","abstract":"Urinary cell-free DNA fragmentation patterns in Dnase1 and Dnase1l3 deficient mice","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004899","title":"Personalised therapy with MEK inhibition leads to a sustained complete response in an adolescent patient with a recurrent malignant peripheral nerve sheath tumor","description":"The prognosis of recurrent malignant peripheral nerve sheath tumors (MPNST) is dismal, with surgical resection being the only definitive salvage therapy. Treatment with chemo-radiation approaches has not significantly improved patient outcomes. Similarly, trials of therapies targeting MPNST genomic drivers have thus far been unsuccessful. Improved understanding of the molecular pathogenesis of MPNST indicates frequent activation of the mitogen activated protein kinase (MAPK) cell signaling pathway. MEK inhibitors have shown activity in preclinical studies; however, their clinical efficacy has not been reported to date. We describe here a  case of sustained complete response to MEK inhibition in an adolescent patient with a recurrent metastatic MPNST with multiple alterations in the MAPK pathway, guided by a precision oncology approach.","abstract":"The prognosis of recurrent malignant peripheral nerve sheath tumors (MPNST) is dismal, with surgical resection being the only definitive salvage therapy. Treatment with chemo-radiation approaches has not significantly improved patient outcomes. Similarly, trials of therapies targeting MPNST genomic drivers have thus far been unsuccessful. Improved understanding of the molecular pathogenesis of MPNST indicates frequent activation of the mitogen activated protein kinase (MAPK) cell signaling pathway. MEK inhibitors have shown activity in preclinical studies; however, their clinical efficacy has not been reported to date. We describe here a  case of sustained complete response to MEK inhibition in an adolescent patient with a recurrent metastatic MPNST with multiple alterations in the MAPK pathway, guided by a precision oncology approach.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-14T01:29:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004900","title":"Single-cell chromatin accessibility landscape identifies tissue repair program in human regulatory T cells","description":"Studies over the past decade characterized murine regulatory T cells (Tregs) with the capacity to promote tissue regeneration. In humans, such a population of tissue-repair Treg cells has not been discovered yet. Using single-cell chromatin accessibility profiles of murine and human tissue Treg cells, we defined a species-conserved and microbiota-independent repair Treg signature, with a prevailing footprint of the transcription factor BATF. Combining this signature with gene expression profiling and TCR fate mapping, we identified a population of tissue-like Treg cells in peripheral blood, characterized by the expression of BATF, CCR8 and HLA-DR. Human BATF+CCR8+ Treg cells from normal skin and adipose tissue shared features with tumor-resident Treg and tissue T-follicular helper (Tfh) cells. Inducing a Tfh-like differentiation program in naive Treg cells partially recapitulated human tissue Treg characteristics, including enhanced wound healing potential","abstract":"Studies over the past decade characterized murine regulatory T cells (Tregs) with the capacity to promote tissue regeneration. In humans, such a population of tissue-repair Treg cells has not been discovered yet. Using single-cell chromatin accessibility profiles of murine and human tissue Treg cells, we defined a species-conserved and microbiota-independent repair Treg signature, with a prevailing footprint of the transcription factor BATF. Combining this signature with gene expression profiling and TCR fate mapping, we identified a population of tissue-like Treg cells in peripheral blood, characterized by the expression of BATF, CCR8 and HLA-DR. Human BATF+CCR8+ Treg cells from normal skin and adipose tissue shared features with tumor-resident Treg and tissue T-follicular helper (Tfh) cells. Inducing a Tfh-like differentiation program in naive Treg cells partially recapitulated human tissue Treg characteristics, including enhanced wound healing potential","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-14T12:19:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004901","title":"Total RNA-Sequencing of patient-derived xenograft models of myxoid liposarcoma","description":null,"abstract":"Illumina total RNA-Sequencing was performed on 40 samples of two patient-derived xenograft models of myxoid liposarcoma, namely ML017 and ML017-ET, the first responsive to trabectedin the latter resistant to treatment. Sequencing libraries were generated with NextSeq500 with at least 60M reads per sample. Both models underwent the same treatment schedule either with trabectedin or doxorubicin.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004902","title":"Whole genome sequencing of germline DNA from 8 patients with adult granulosa cell tumors (from blood or saliva)","description":"Whole genome sequencing BAMs of DNA obtained from blood/saliva of 8 patients with adult granulosa cell tumors. These patients come from four independent families, with each family having 2 affected family members.","abstract":"Whole genome sequencing BAMs of DNA obtained from blood/saliva of 8 patients with adult granulosa cell tumors. These patients come from four independent families, with each family having 2 affected family members.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-14T12:55:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004903","title":"Finding structural variation and functional consequences from the primary leukemia cells (AML) at the single-cell level","description":"In this study, we aimed to identify somatic structural variation of acute myeloid leukemia (AML) at the single-cell level and investigate its direct consequence on the nucleosome occupancy using scNOVA approach. For this purpose, we performed strand-specific single-cell sequencing of primary leukemia samples from 32 year old male donor.","abstract":"In this study, we aimed to identify somatic structural variation of acute myeloid leukemia (AML) at the single-cell level and investigate its direct consequence on the nucleosome occupancy using scNOVA approach. For this purpose, we performed strand-specific single-cell sequencing of primary leukemia samples from 32 year old male donor.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-14T14:05:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004904","title":"Oncolytic virotherapy mediated anti-tumor response in primary cutaneous B-cell lymphoma: a single-cell perspective","description":null,"abstract":"We analyzed fine-needle aspirate (FNA) samples of T-VEC-treated primary cutaneous B-cell lymphoma patients. FNAs were taken from injected and non-injected lesions before and at several time points after the patient's first injection. The study aimed to describe the dynamics of the viral infection, characterize the changes in the tumor microenvironment caused by T-VEC-treatment compare injected and non-injected lesions and identify the mechanism of action.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-14T15:34:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004905","title":"Dual targeting of polyamine synthesis and uptake in diffuse intrinsic pontine gliomas","description":"Diffuse intrinsic pontine glioma (DIPG) is an incurable malignant childhood brain tumour, with no active systemic therapies and a 5-year survival of less than 1%. Polyamines are small organic polycations that are essential for DNA replication, translation and cell proliferation. Ornithine decarboxylase 1 (ODC1), the rate limiting enzyme in polyamine synthesis, is irreversibly inhibited by difluoromethylornithine (DFMO). Herein we show that polyamine synthesis is upregulated in DIPG, leading to sensitivity to DFMO. DIPG cells compensate for ODC1 inhibition by upregulation of the polyamine transporter SLC3A2. Treatment with the polyamine transporter inhibitor AMXT 1501 reduced uptake of polyamines in DIPG cells, and co-administration of AMXT 1501 and DFMO led to potent in vitro activity, and significant extension of survival in three aggressive DIPG orthotopic animal models. Collectively, these results demonstrate the potential of dual targeting of polyamine synthesis and uptake as a therapeutic strategy for incurable DIPG.","abstract":"Diffuse intrinsic pontine glioma (DIPG) is an incurable malignant childhood brain tumour, with no active systemic therapies and a 5-year survival of less than 1%. Polyamines are small organic polycations that are essential for DNA replication, translation and cell proliferation. Ornithine decarboxylase 1 (ODC1), the rate limiting enzyme in polyamine synthesis, is irreversibly inhibited by difluoromethylornithine (DFMO). Herein we show that polyamine synthesis is upregulated in DIPG, leading to sensitivity to DFMO. DIPG cells compensate for ODC1 inhibition by upregulation of the polyamine transporter SLC3A2. Treatment with the polyamine transporter inhibitor AMXT 1501 reduced uptake of polyamines in DIPG cells, and co-administration of AMXT 1501 and DFMO led to potent in vitro activity, and significant extension of survival in three aggressive DIPG orthotopic animal models. Collectively, these results demonstrate the potential of dual targeting of polyamine synthesis and uptake as a therapeutic strategy for incurable DIPG.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-15T03:29:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004906","title":"Mutational Landscape of Plasmablastic Lymphoma","description":"Plasmablastic lymphoma (PBL) represents a clinically heterogeneous subtype of aggressive B-cell non-Hodgkin lymphoma. Although targeted sequencing studies and a single center whole exome sequencing (WES) study in HIV+ patients recently revealed several genes, associated with PBL pathogenesis, the global mutational landscape and transcriptional profile of PBL remain elusive. To inform on disease-associated mutational drivers, mutational patterns and perturbed pathways in HIV+ and HIV- PBL we performed WES and RNA-sequencing (RNA-seq) of 34 PBL tumors.","abstract":"Plasmablastic lymphoma (PBL) represents a clinically heterogeneous subtype of aggressive B-cell non-Hodgkin lymphoma. Although targeted sequencing studies and a single center whole exome sequencing (WES) study in HIV+ patients recently revealed several genes, associated with PBL pathogenesis, the global mutational landscape and transcriptional profile of PBL remain elusive. To inform on disease-associated mutational drivers, mutational patterns and perturbed pathways in HIV+ and HIV- PBL we performed WES and RNA-sequencing (RNA-seq) of 34 PBL tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-15T07:05:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004907","title":"Blood RNA-seq from Mexican DMD patients and healthy controls","description":"These data are part of a study that aimed to assess the potential of blood RNA-seq to track non-invasively disease progression for DMD. In particular, here we focus on a study designed to compare gene expression in blood from DMD patients to that of healthy controls. These data are analysed in the following manuscript:\nSignorelli, M., Ebrahimpoor, M. et al. (accepted). Peripheral blood transcriptome profiling enables monitoring disease progression in dystrophic mice and patients. To appear in EMBO Molecular Medicine.","abstract":"These data are part of a study that aimed to assess the potential of blood RNA-seq to track non-invasively disease progression for DMD. In particular, here we focus on a study designed to compare gene expression in blood from DMD patients to that of healthy controls. These data are analysed in the following manuscript:\nSignorelli, M., Ebrahimpoor, M. et al. (accepted). Peripheral blood transcriptome profiling enables monitoring disease progression in dystrophic mice and patients. To appear in EMBO Molecular Medicine.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-15T12:06:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004908","title":"Mutations in SKI in Shprintzen-Goldberg syndrome lead to attenuated TGFB responses through SKI stabilization","description":null,"abstract":"Shprintzen-Goldberg syndrome (SGS) is a multisystemic connective tissue disorder, with considerable clinical overlap with Marfan and Loeys-Dietz syndromes. These syndromes have commonly been associated with enhanced TGFB signaling. In SGS patients, heterozygous point mutations have been mapped to the transcriptional corepressor SKI, which is a negative regulator of TGFB signaling that is rapidly degraded upon ligand stimulation. The molecular consequences of these mutations, however, are not understood. Here we use a combination of structural biology, genome editing and biochemistry to show that SGS mutations in SKI abolish its binding to phosphorylated SMAD2 and SMAD3. This results in stabilization of SKI and consequently attenuation of TGFB responses, in both knockin cells expressing an SGS mutation, and in fibroblasts from SGS patients. Thus, we reveal that SGS is associated with an attenuation of TGFB-induced transcriptional responses, and not enhancement, which has important implications for other Marfan-related syndromes.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-15T18:19:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004909","title":"Single cell multi-omic data of glioblastoma evolution under therapy","description":"We report a single-cell multi-omics atlas of GBM longitudinal specimens that represents decades of biobanking. We identify novel cell-intrinsic and cell-extrinsic targets for therapy development which we validate in situ and in low-passage patient-derived cell lines. We identify novel genetic correlates of the mesenchymal cellular phenotype. These studies integrate disparate findings in the literature around\nhypermutation status and immunogenicity as well as the source of the mesenchymal shift at recurrence.","abstract":"We report a single-cell multi-omics atlas of GBM longitudinal specimens that represents decades of biobanking. We identify novel cell-intrinsic and cell-extrinsic targets for therapy development which we validate in situ and in low-passage patient-derived cell lines. We identify novel genetic correlates of the mesenchymal cellular phenotype. These studies integrate disparate findings in the literature around\nhypermutation status and immunogenicity as well as the source of the mesenchymal shift at recurrence.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-16T01:02:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004910","title":"Whole genome sequencing of glioblastoma","description":null,"abstract":"Whole genome sequencing of glioblastoma","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004911","title":"Barcoded_scRNAseq","description":"This study aims to test the effectiveness of retroviral lineage barcoding in allowing pooled single Cell sequencing study design.  Isogenic lines with and without engineered mutations are infected with non-targeting gRNA vectors, to permanently label the cells.  After pooling of cells, a custom 5' 10X scRNAseq is run to identify not only expressed genes, but also expressed guide sequences that act as a barcode for clone of origin.\n\nThese data will assess how well the gRNA barcodes are detected after neural differentiation, in preparation for more complex study designs in the future.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing","abstract":"This study aims to test the effectiveness of retroviral lineage barcoding in allowing pooled single Cell sequencing study design.  Isogenic lines with and without engineered mutations are infected with non-targeting gRNA vectors, to permanently label the cells.  After pooling of cells, a custom 5' 10X scRNAseq is run to identify not only expressed genes, but also expressed guide sequences that act as a barcode for clone of origin.  These data will assess how well the gRNA barcodes are detected after neural differentiation, in preparation for more complex study designs in the future.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004912","title":"Neutrophils infected with Leishmania donovani","description":"In the context of studying visceral leishmaniasis, neutrophils infected with Leishmania donovani have been compared to uninfected neutrophils. Compared time points are 0, 6 and 24 hours post infection. Neutrophils of three human donors have been used. Overall 6 samples for infected neutrophils at time point 6 hours and 6 samples for infected neutrophils at time point 24 hours exist, including three biological samples and two technical samples. Uninfected neutrophils represent 3 samples at time point 0 hours, 3 samples at time point 6 hours and 3 samples at time point 24 hours. Transcriptome of Leishmania donovani culture has been assessed in two replicates.","abstract":"In the context of studying visceral leishmaniasis, neutrophils infected with Leishmania donovani have been compared to uninfected neutrophils. Compared time points are 0, 6 and 24 hours post infection. Neutrophils of three human donors have been used. Overall 6 samples for infected neutrophils at time point 6 hours and 6 samples for infected neutrophils at time point 24 hours exist, including three biological samples and two technical samples. Uninfected neutrophils represent 3 samples at time point 0 hours, 3 samples at time point 6 hours and 3 samples at time point 24 hours. Transcriptome of Leishmania donovani culture has been assessed in two replicates.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-17T06:44:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004913","title":"ChIP-seq of plasma cell-free nucleosomes identifies gene expression programs of the cells-of-origin","description":"Cell-free DNA in human plasma provides access to molecular information about the pathological processes in the organs or tumors from which it originates. These DNA fragments are derived from fragmented chromatin in dying cells, and retain some of the cell of origin histone modifications. Here, we apply chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin modifications followed by sequencing (cfChIP-seq) to 268 human samples. In healthy donors, we identified bone marrow megakaryocytes, but not erythroblasts, as major contributors to the cfDNA pool. In patients with a range of liver diseases, we show that we can identify pathology-related changes in hepatocyte transcriptional programs. In metastatic colorectal carcinoma patients, we detected clinically relevant, and patient-specific information, including transcriptionally active HER2 amplifications. Altogether, cfChIP-seq using low sequencing depth, provides systemic and genome-wide information, can inform diagnosis, and facilitate interrogation of physiological and pathological processes using blood samples.","abstract":"Cell-free DNA in human plasma provides access to molecular information about the pathological processes in the organs or tumors from which it originates. These DNA fragments are derived from fragmented chromatin in dying cells, and retain some of the cell of origin histone modifications. Here, we apply chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin modifications followed by sequencing (cfChIP-seq) to 268 human samples. In healthy donors, we identified bone marrow megakaryocytes, but not erythroblasts, as major contributors to the cfDNA pool. In patients with a range of liver diseases, we show that we can identify pathology-related changes in hepatocyte transcriptional programs. In metastatic colorectal carcinoma patients, we detected clinically relevant, and patient-specific information, including transcriptionally active HER2 amplifications. Altogether, cfChIP-seq using low sequencing depth, provides systemic and genome-wide information, can inform diagnosis, and facilitate interrogation of physiological and pathological processes using blood samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-17T10:46:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004914","title":"OTAR_LUNG_spatial","description":"Interrogation of cell populations of the human lung.","abstract":"The immune cell component of the lungs is important to assure adequate protection against pathogens and allergens. ln order to better understand the immune makeup of\nhumans lungs we will use a series of molecular and cellular techniques to and how these populations are related to circulating blood immune cells.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004915","title":"Selective Elimination of Immunosuppressive T cells in Patients with Multiple Myeloma","description":null,"abstract":"Elimination of suppressive T cells may enable and enhance cancer immunotherapy. Here, we demonstrate that the cell membrane protein SLAMF7 was highly expressed on immunosuppressive CD8+CD28-CD57+ Tregs in multiple myeloma (MM). SLAMF7 expression associated with T cell exhaustion surface markers and exhaustion-related transcription factor signatures. T cells from patients with a high frequency of SLAMF7+CD8+ T cells exhibited decreased immunoreactivity towards the MART-1aa26–35*A27L antigen. A monoclonal anti-SLAMF7 antibody (elotuzumab) specifically depleted SLAMF7+CD8+ T cells in vitro and in vivo via macrophage-mediated antibody-dependent cellular phagocytosis (ADCP). Anti-SLAMF7 treatment of MM patients depleted suppressive T cells in peripheral blood. These data highlight SLAMF7 as a marker for suppressive CD8+ Treg and suggest that anti-SLAMF7 antibodies can be used to boost anti-tumoral immune responses in cancer patients.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-17T13:58:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004916","title":"HCA_Adult_WSSS_spatial","description":"Interrogation of adult human gut using spatial transcriptomics","abstract":"In this study, we will apply spatial methods such as 10X Visium and whole-mount RNAscope to interrogate the role of immune cells in the adult human gut.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004917","title":"HCA_Lung_Foetal_MRC_RNA","description":"Cell atlas of human foetal lung","abstract":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. This specific project will assess epigenetic and transcriptomic landscape of cells of the developing human lung. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions. Deep Dive for Foetal Lung RNA only. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004918","title":"Oxford Nanopore RNA sequencing for HLA typing","description":"A targeted RNA-based method for typing of 12 classical HLA genes using Oxford Nanopore sequencing. In the method,  were enriched HLA genes from cDNA of 50 individuals using gene-specific reverse primers. The library molecules were then barcoded, pooled into 2 separate gene pools, and sequenced on MinION R9.4 SpotON flow cells.","abstract":"A targeted RNA-based method for typing of 12 classical HLA genes using Oxford Nanopore sequencing. In the method,  were enriched HLA genes from cDNA of 50 individuals using gene-specific reverse primers. The library molecules were then barcoded, pooled into 2 separate gene pools, and sequenced on MinION R9.4 SpotON flow cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-18T06:44:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004919","title":"HCA_Thymus_Foetal_WSSS_RNA","description":"Interrogation of foetal thymus and associated tissues","abstract":"Cell atlas of foetal Thymus - The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through; genetic and genomic analysis, expression analysis, non-identifiable video imaging and cell line and organoid production, as well as, computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequently validate these findings in situ using spatial genomic and imaging technologies e.g. immunohistochemistry, RNAscope, in situ sequencing and spatial transcriptomic analyses.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004920","title":"Single_cell_DNA_and_RNA_seq_of_Tauopathy_human_postmortem_brain_DNA","description":"Single-cell DNA and RNA-seq of Tauopathy human postmortem brain","abstract":"To characterise genomic instability and potential functional consequences in human tauopathy brains, we performed single-nucleus DNA and RNA sequencing.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004921","title":"Single_cell_DNA_and_RNA_seq_of_Tauopathy_human_postmortem_brain_RNA","description":"Single-cell DNA and RNA-seq of Tauopathy human postmortem brain","abstract":"To characterise genomic instability and potential functional consequences in human tauopathy brains, we performed single-nucleus DNA and RNA sequencing.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004922","title":"Single_molecule_somatic_mutation_detection_comparison_DuplexSeq","description":"Both PacBio CCS sequencing and duplex sequencing allows single molecule somatic mutation, but data from these two independent approaches have not been compared and contrasted. To enable systematic comparison of the two approaches, we are sequencing PD47269d (cord blood) and PD48473b (82 year old blood) to determine the error rate, advantages and disadvantages of each method, and the limit of detection.","abstract":"Systematic comparison of PacBio CCS sequncing and duplex sequencing for single molecule somatic mutation detection.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004923","title":"RNAseq_budded_vs_cystic_organoids","description":"The aim of this project is to meaure the host transcriptional response to bacterial toxins and whole bacteria to compare against naive cells and toxin vs bacterial responses.\nThe cells being used will be small intestinal organoids derived from the cell line Kolf-2 using previously published protocols to differentiate the stem cells into small intestinal organoids.\n\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"RNAseq looking at differences between different morphologies of small intestinal organoids.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004924","title":"Genotypes of psychosis cases and controls","description":null,"abstract":"Genotypes in PLINK format of psychosis cases and controls collected by Work Package 2 and 6 of the EUGEI study. The study was designed to detect the interactive genetic, clinical and environmental determinants involved in the development, severity and outcome of psychosis and schizophrenia.","study_type":"Population Genomics","pubmed_ids":[31059627],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004925","title":"Finding structural variation and functional consequences from the primary leukemia cells (CLL) at the single-cell level","description":"In this study, we aimed to identify somatic structural variation of chronic lymphocytic leukemia (CLL) at the single-cell level and investigate its direct consequence on the nucleosome occupancy using scNOVA approach. For this purpose, we performed strand-specific single-cell sequencing of primary leukemia samples from 63-year-old female patient.","abstract":"In this study, we aimed to identify somatic structural variation of chronic lymphocytic leukemia (CLL) at the single-cell level and investigate its direct consequence on the nucleosome occupancy using scNOVA approach. For this purpose, we performed strand-specific single-cell sequencing of primary leukemia samples from 63-year-old female patient.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-20T11:48:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004926","title":"Mutational consequences of hematopoietic stem cell transplantation in humans","description":null,"abstract":"Genetic instability is a major concern for the successful application of stem cells in regenerative medicine. However, the mutational consequences of the most commonly applied stem cell therapy in humans, hematopoietic stem cell transplantation (HSCT), remain unknown. Here, we characterized by whole genome sequencing the genome-wide mutation burden of hematopoietic stem and progenitor cells (HSPCs) of human HSCT recipients and their donors. We demonstrate that the majority of transplanted HSPCs did not display altered mutation accumulation. However, in some HSCT recipients, we identified multiple HSPCs with increased mutation burden after transplantation. This increase could be attributed exclusively to a novel mutational signature, which reflects aberrant DNA replication. Using a machine-learning approach, we detected this signature in cancer genomes of patients who received HSCT or a solid organ transplantation earlier in life. Our results show that HSCT can be associated with enhanced mutagenicity, which may ultimately contribute to carcinogenesis.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-21T08:31:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004927","title":"Short and long-read sequencing of Brugada syndrome samples","description":"Genome-wide association studies (GWAS) are instrumental in identifying loci with an impact on human traits and disease. Typically, however, most GWAS information is considered redundant as it is based on neighboring single-nucleotide variants (SNVs) in strong linkage disequilibrium (LD). In this context, besides the most significant hit (lead SNV) in every trait- or disease-associated locus, the rest of GWAS hits are often marginally reported, examined, or exploited. To interrogate the value of integrating the information provided by the full set of GWAS hits and fine-mapping haplotypes containing these SNVs, here we focused on a locus repeatedly associated with traits of the cardiac electrical conduction system and arrhythmia (SCN5A-SCN10A). We found that the same SNV can exhibit differing associations depending on haplotype. Thus, these analyses provide corroborative evidence that assuming redundancy among neighboring GWAS hits has the risk of missing critical disease-risk associations.","abstract":"Genome-wide association studies (GWAS) are instrumental in identifying loci with an impact on human traits and disease. Typically, however, most GWAS information is considered redundant as it is based on neighboring single-nucleotide variants (SNVs) in strong linkage disequilibrium (LD). In this context, besides the most significant hit (lead SNV) in every trait- or disease-associated locus, the rest of GWAS hits are often marginally reported, examined, or exploited. To interrogate the value of integrating the information provided by the full set of GWAS hits and fine-mapping haplotypes containing these SNVs, here we focused on a locus repeatedly associated with traits of the cardiac electrical conduction system and arrhythmia (SCN5A-SCN10A). We found that the same SNV can exhibit differing associations depending on haplotype. Thus, these analyses provide corroborative evidence that assuming redundancy among neighboring GWAS hits has the risk of missing critical disease-risk associations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-21T18:44:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004928","title":"Single-cell RNA-seq of bronchoalveolar lavage (BAL) fluid in severe COVID-19 and SARS-CoV-2 stimulated classical blood monocytes","description":"We analyzed pulmonary monocyte and macrophage responses as well as and pulmonary pathology in two cohorts of patients with COVID-19 associated ARDS. Monocyte-derived macrophages accumulated in the lung during ARDS and acquired a profibrotic signature, characterized by high expression of known fibrogenic factors like TGFB1, SPP1 and LGMN. COVID-19 associated macrophages showed highly significant transcriptional similarity with profibrotic macrophage populations identified in idiopathic pulmonary fibrosis (IPF). Notably, overnight exposure to SARS-CoV-2, but not influenza A virus or viral RNA analogues, induced a similar phenotype in human monocytes from healthy volunteers in vitro. Patients with severe COVID-19 associated ARDS showed clear clinical, radiographic and histopathological features of scarring and fibrotic tissue remodeling. In conclusion, SARS-CoV-2 triggers profibrotic macrophage responses, fibroproliferative ARDS, and lung fibrosis","abstract":"We analyzed pulmonary monocyte and macrophage responses as well as and pulmonary pathology in two cohorts of patients with COVID-19 associated ARDS. Monocyte-derived macrophages accumulated in the lung during ARDS and acquired a profibrotic signature, characterized by high expression of known fibrogenic factors like TGFB1, SPP1 and LGMN. COVID-19 associated macrophages showed highly significant transcriptional similarity with profibrotic macrophage populations identified in idiopathic pulmonary fibrosis (IPF). Notably, overnight exposure to SARS-CoV-2, but not influenza A virus or viral RNA analogues, induced a similar phenotype in human monocytes from healthy volunteers in vitro. Patients with severe COVID-19 associated ARDS showed clear clinical, radiographic and histopathological features of scarring and fibrotic tissue remodeling. In conclusion, SARS-CoV-2 triggers profibrotic macrophage responses, fibroproliferative ARDS, and lung fibrosis","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-23T14:12:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004929","title":"Whole genome sequencing delineates regulatory, structural, and cryptic splice variants in early onset cardiomyopathy","description":"Cardiomyopathy (CMP) is a heritable disorder. Over 50% cases are gene-elusive on clinical gene panel testing. The contribution of variants in non-coding DNA elements that result in cryptic splicing and regulate gene expression has not been explored. We analyzed whole genome sequencing (WGS) data in a discovery cohort of 209 pediatric CMP patients and 1,953 independent replication genomes and exomes. We searched for protein-coding variants, and non-coding variants predicted to affect the function or expression of genes. Thirty-nine % cases harbored pathogenic coding variants in known CMP genes, and 5% harbored high-risk loss-of-function (LoF) variants in additional candidate CMP genes. Fifteen % harbored high-risk regulatory variants in promoters and enhancers of CMP genes (Odds ratio 2.25, p=6.70×10-7 versus controls). Genes involved in α-dystroglycan glycosylation (FKTN, DTNA) and desmosomal signaling (DSC2, DSG2) were most highly enriched for regulatory variants (Odds ratio 6.7-58.1). Functional effects were confirmed in patient myocardium and reporter assays in human cardiomyocytes, and in zebrafish CRISPR knockouts. We provide strong evidence for the genomic contribution of functionally active variants in new genes and in regulatory elements of known CMP genes to early-onset CMP.","abstract":"Cardiomyopathy (CMP) is a heritable disorder. Over 50% cases are gene-elusive on clinical gene panel testing. The contribution of variants in non-coding DNA elements that result in cryptic splicing and regulate gene expression has not been explored. We analyzed whole genome sequencing (WGS) data in a discovery cohort of 209 pediatric CMP patients and 1,953 independent replication genomes and exomes. We searched for protein-coding variants, and non-coding variants predicted to affect the function or expression of genes. Thirty-nine % cases harbored pathogenic coding variants in known CMP genes, and 5% harbored high-risk loss-of-function (LoF) variants in additional candidate CMP genes. Fifteen % harbored high-risk regulatory variants in promoters and enhancers of CMP genes (Odds ratio 2.25, p=6.70×10-7 versus controls). Genes involved in α-dystroglycan glycosylation (FKTN, DTNA) and desmosomal signaling (DSC2, DSG2) were most highly enriched for regulatory variants (Odds ratio 6.7-58.1). Functional effects were confirmed in patient myocardium and reporter assays in human cardiomyocytes, and in zebrafish CRISPR knockouts. We provide strong evidence for the genomic contribution of functionally active variants in new genes and in regulatory elements of known CMP genes to early-onset CMP.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-23T14:15:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004930","title":"Phase Ib of olaparib and capivasertib","description":"Background:  Combining poly(ADP-ribose) polymerase (PARP) with phosphatidylinositol-3-kinase (PI3K) pathway inhibitors is supported by strong preclinical rationale. We sought to assess safety and a recommended phase 2 dose (RP2D)  for the PARPi olaparib combined with the AKT inhibitor, capivasertib, and evaluate molecular markers of response and resistance.\nMethods: As part of a larger phase 1b trial, we performed a safety lead in of olaparib and capivasertib followed by expansion (n=24) in endometrial, triple negative breast, ovarian, fallopian tube, or peritoneal cancer. Olaparib 300mg orally twice daily and capivasertib orally twice daily on a 4 day on/3 day off schedule were evaluated. Two dose levels (DL) were planned: capivasertib 400mg (DL1); capivasertib 320mg (DL-1). Patients underwent biopsies at baseline and after 28 days.","abstract":"Background:  Combining poly(ADP-ribose) polymerase (PARP) with phosphatidylinositol-3-kinase (PI3K) pathway inhibitors is supported by strong preclinical rationale. We sought to assess safety and a recommended phase 2 dose (RP2D)  for the PARPi olaparib combined with the AKT inhibitor, capivasertib, and evaluate molecular markers of response and resistance.\nMethods: As part of a larger phase 1b trial, we performed a safety lead in of olaparib and capivasertib followed by expansion (n=24) in endometrial, triple negative breast, ovarian, fallopian tube, or peritoneal cancer. Olaparib 300mg orally twice daily and capivasertib orally twice daily on a 4 day on/3 day off schedule were evaluated. Two dose levels (DL) were planned: capivasertib 400mg (DL1); capivasertib 320mg (DL-1). Patients underwent biopsies at baseline and after 28 days.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-25T23:17:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004931","title":"Illumina RNA sequencing for HLA expression qauntification","description":"In this study, we quantified mRNA expression levels of HLA class I and II genes from peripheral blood samples of 50 healthy individuals. The gene- and allele-specific mRNA expression was assessed using unique molecular identifiers, which enabled PCR bias removal and calculation of the number of original mRNA transcripts. We identified differences in mRNA expression between different HLA genes and alleles. Our results suggest that HLA alleles are differentially expressed and these differences in expression levels are quantifiable using RNA sequencing technology.","abstract":"In this study, we quantified mRNA expression levels of HLA class I and II genes from peripheral blood samples of 50 healthy individuals. The gene- and allele-specific mRNA expression was assessed using unique molecular identifiers, which enabled PCR bias removal and calculation of the number of original mRNA transcripts. We identified differences in mRNA expression between different HLA genes and alleles. Our results suggest that HLA alleles are differentially expressed and these differences in expression levels are quantifiable using RNA sequencing technology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-28T10:30:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004932","title":"Characterization of the genomic heterogeneity among the Leishmania infantum strains circulating in the Comunidad Autonoma de Madrid (Spain)","description":null,"abstract":"This study was aimed at the characterization of the genomic heterogeneity among the Leishmania infantum strains circulating in the Comunidad Autonoma de Madrid (Spain). For this purpose, thirteen strains, isolated from leishmaniasis patients, were grown in axenic conditions to obtain genomic DNA. This material was used to Illumina massive sequencing. As a result, the raw data for these 13 isolates were generated, and here are publically available.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004933","title":"The Genetic History of Greenlandic-European contact","description":"The Inuit ancestors of the Greenlandic people arrived in Greenland close to 1000 years ago. Since then, Europeans from many different countries have been present in Greenland. Consequently, the present-day Greenlandic population has ~25% of its genetic ancestry from Europe. In this study, we investigated to what extent different European countries have contributed to this genetic ancestry.","abstract":"The Inuit ancestors of the Greenlandic people arrived in Greenland close to 1000 years ago. Since then, Europeans from many different countries have been present in Greenland. Consequently, the present-day Greenlandic population has ~25% of its genetic ancestry from Europe. In this study, we investigated to what extent different European countries have contributed to this genetic ancestry.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2020-12-31T19:59:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004934","title":"Detection of Gene Fusions using Targeted Next-Generation Sequencing – a Comparative Evaluation","description":null,"abstract":"Gene fusions represent promising targets for cancer therapy in lung cancer. Reliable detection of multiple gene fusions is therefore essential. Here, five commercially available parallel sequencing assays were evaluated for their ability to detect gene fusions in eight cell lines and 18 FFPE tissue samples carrying a variety of known gene fusions. Four RNA-based assays and one DNA-based assay were compared; two were hybrid capture-based, TruSight Tumor 170 Assay (Illumina) and SureSelect XT HS Custom Panel (Agilent), and three were amplicon-based, Archer FusionPlex Lung Panel (ArcherDX), QIAseq RNAscan Custom Panel (Qiagen) and Oncomine Focus Assay (Thermo Fisher Scientific).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-04T18:27:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004935","title":"Single Cell Dissection of the Tumour Microenvironment Reveals Dynamic Interplay Shaping the Tumour Immunity Continuum in Ovarian Cancer","description":"Diverse tumour immune phenotypes with distinct T cell infiltration patterns result in different responses to cancer immunotherapies. However, the key determinants and biology underpinning these phenotypes remain elusive. Here, we provide a high-resolution dissection of the tumour microenvironment representative of different tumour immune phenotypes. By performing single-cell RNA sequencing (scRNAseq) of the tumour, immune, and stromal compartments from 15 ovarian cancer patients, we characterized the diverse cellular and functional phenotypes, as well as dynamic interplay within and between these components. Infiltrated and excluded tumours markedly differed from desert tumours in several tumour cell intrinsic features, including high interferon response, antigen presentation and oxidative phosphorylation. Moreover, these tumours were characterized by tumour associated macrophage (TAM)-like myeloid subsets, while desert tumours were enriched in myeloid derived suppressive cell (MDSC)-like myeloid subsets. Infiltrated and excluded tumours differed in their T cell composition and fibroblast subsets. While dysfunctional CD8+ GZMB T cells and IL1-activated fibroblasts (IL1 CAFs) were associated with infiltrated tumours, pre-dysfunctional CD8+ GZMK T cells and TGFB-activated fibroblasts (TGFB CAFs) were enriched in excluded tumours. These findings validated in bulk transcriptomic profiles of 1071 ovarian tumours and using in situ hybridization. Furthermore, our study revealed chemokine receptor-ligand interactions within and across compartments as potential mechanisms mediating immune cell infiltration, exemplified by the tumour cell-T cell crosstalk via a CXC16-CXCR6 axis, stromal-immune cell crosstalk via CXCL12/14-CXCR4 signalling, and TAM-like macrophage-T cell crosstalk through CXCR3-CXCL9/10/11 signalling. Our in-depth characterization of the tumour environment and intercellular interactions provides novel insights into potential molecular mechanisms that shape the distinct biology of tumour immune phenotypes. Our findings may inform novel therapeutic strategies for potentially shifting tumours along the immunity continuum to improve clinical benefit from cancer immunotherapies.","abstract":"Diverse tumour immune phenotypes with distinct T cell infiltration patterns result in different responses to cancer immunotherapies. However, the key determinants and biology underpinning these phenotypes remain elusive. Here, we provide a high-resolution dissection of the tumour microenvironment representative of different tumour immune phenotypes. By performing single-cell RNA sequencing (scRNAseq) of the tumour, immune, and stromal compartments from 15 ovarian cancer patients, we characterized the diverse cellular and functional phenotypes, as well as dynamic interplay within and between these components. Infiltrated and excluded tumours markedly differed from desert tumours in several tumour cell intrinsic features, including high interferon response, antigen presentation and oxidative phosphorylation. Moreover, these tumours were characterized by tumour associated macrophage (TAM)-like myeloid subsets, while desert tumours were enriched in myeloid derived suppressive cell (MDSC)-like myeloid subsets. Infiltrated and excluded tumours differed in their T cell composition and fibroblast subsets. While dysfunctional CD8+ GZMB T cells and IL1-activated fibroblasts (IL1 CAFs) were associated with infiltrated tumours, pre-dysfunctional CD8+ GZMK T cells and TGFB-activated fibroblasts (TGFB CAFs) were enriched in excluded tumours. These findings validated in bulk transcriptomic profiles of 1071 ovarian tumours and using in situ hybridization. Furthermore, our study revealed chemokine receptor-ligand interactions within and across compartments as potential mechanisms mediating immune cell infiltration, exemplified by the tumour cell-T cell crosstalk via a CXC16-CXCR6 axis, stromal-immune cell crosstalk via CXCL12/14-CXCR4 signalling, and TAM-like macrophage-T cell crosstalk through CXCR3-CXCL9/10/11 signalling. Our in-depth characterization of the tumour environment and intercellular interactions provides novel insights into potential molecular mechanisms that shape the distinct biology of tumour immune phenotypes. Our findings may inform novel therapeutic strategies for potentially shifting tumours along the immunity continuum to improve clinical benefit from cancer immunotherapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-05T00:19:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004936","title":"Single-cell analysis of the multicellular ecosystem in viral carcinogenesis by HTLV-1","description":"Single-cell RNA sequencing (scRNA-seq), antibody-derived tag sequencing (scADT-seq) and T/B-cell receptor (TCR/BCR) sequencing (scTCR/BCR-seq) on  peripheral blood mononuclear cells (PBMCs) obtained from 30 ATL patients (34 samples including 4 sequential ones), 11 HTLV-1-infected asymptomatic carriers, and 4 healthy donors.","abstract":"Single-cell RNA sequencing (scRNA-seq), antibody-derived tag sequencing (scADT-seq) and T/B-cell receptor (TCR/BCR) sequencing (scTCR/BCR-seq) on  peripheral blood mononuclear cells (PBMCs) obtained from 30 ATL patients (34 samples including 4 sequential ones), 11 HTLV-1-infected asymptomatic carriers, and 4 healthy donors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-05T01:26:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004937","title":"Comparison of the diagnostic yield of aCGH and NGS across different neurodevelopmental disorders","description":null,"abstract":"Current recommendations for the genetic diagnosis of neurodevelopmental disorders (NDDs) do not include the use of next generation sequencing (NGS) and are still based on chromosomal microarrays, such as comparative genomic hybridization array (aCGH). The present study compares the diagnostic yield obtained by aCGH and clinical exome sequencing in NDD globally and its spectrum of disorders. To that end, 1412 patients clinically diagnosed with NDDs and studied with aCGH were classified into phenotype categories: Global developmental delay/intellectual disability (GDD/ID); autism spectrum disorder (ASD); and Other NDDs. These categories were further subclassified into subcategories, based on the most frequent accompanying signs and symptoms: isolated forms, forms with epilepsy; forms with micro or macrocephaly and syndromic forms. A subset of 245 patients of the 1412 were subjected to clinical exome sequencing. Diagnostic yield of aCGH and clinical exome sequencing, expressed as the number of solved cases, was compared for each phenotype category and subcategory. Clinical exome sequencing was superior than aCGH for all cases except for isolated ASD, with no cases solved by NGS. Globally, clinical exome sequencing solved 20% of cases (versus 5.7% by aCGH) and the diagnostic yield was highest for all forms of GDD/ID and lowest for Other NDDs (7.1% versus 1.4% by aCGH) and ASD (6.1% versus 3% by aCGH). In the majority of cases, diagnostic yield was higher in the phenotype subcategories than in the mother category. These results support the use of NGS as the first-tier test in the diagnostic algorithm of all NDDs followed by aCGH when necessary.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004938","title":"Human_iHO_and_CTX","description":"We are investigating the 48hr response of iPS derived intestinal organoids (iHO) to treatment with CTX either administered externally in the medium or internally by micro-injection\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We will analyse the transcriptomic data from WT iHO with and without 48hrs of treatment with CTX","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004939","title":"Tissue and plasma RNA from esophageal cancer and precursor lesions","description":"In the past decades, the incidence of esophageal adenocarcinoma has increased dramatically in Western populations. Better understanding of disease etiology along with the identification of novel prognostic and predictive biomarkers are urgently needed to improve the dismal survival probabilities. Here, we performed comprehensive RNA (both coding and non-coding) profiling in various samples from 17 patients diagnosed with esophageal adenocarcinoma, high-grade dysplastic or non-dysplastic Barrett’s esophagus. Per patient, a blood plasma sample, and a healthy esophageal and disease tissue sample were included. In total, this comprehensive dataset consists of 102 RNA-seq libraries from 51 samples. This unique resource allows for discovery of novel biomarkers and disease mechanisms, comparison of tissue and liquid biopsy profiles, integration of coding and non-coding RNA patterns, and can serve as a validation dataset in other RNA landscaping studies. Moreover, structural RNA differences can be identified in this dataset, including protein coding mutations fusion genes, and circular RNAs.","abstract":"In the past decades, the incidence of esophageal adenocarcinoma has increased dramatically in Western populations. Better understanding of disease etiology along with the identification of novel prognostic and predictive biomarkers are urgently needed to improve the dismal survival probabilities. Here, we performed comprehensive RNA (both coding and non-coding) profiling in various samples from 17 patients diagnosed with esophageal adenocarcinoma, high-grade dysplastic or non-dysplastic Barrett’s esophagus. Per patient, a blood plasma sample, and a healthy esophageal and disease tissue sample were included. In total, this comprehensive dataset consists of 102 RNA-seq libraries from 51 samples. This unique resource allows for discovery of novel biomarkers and disease mechanisms, comparison of tissue and liquid biopsy profiles, integration of coding and non-coding RNA patterns, and can serve as a validation dataset in other RNA landscaping studies. Moreover, structural RNA differences can be identified in this dataset, including protein coding mutations fusion genes, and circular RNAs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-06T12:30:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004940","title":"Sensitive and robust liquid biopsy-based detection of PIK3CA mutations","description":"Over the last years, the treatment of hormone receptor-positive metastatic breast cancer patients has dramatically changed. Combination strategies attempting to overcome resistance to endocrine therapy such as targeting the PI3 kinase pathway are gaining importance. The phase III SOLAR-1 trial demonstrated the benefit of the addition of alpelisib to fulvestrant, thereby providing further clinical evidence of the increasing importance of PIK3CA testing. Here, we performed a comparison of liquid biopsy and tissue-based detection of PIK3CA mutations in HR-positive metastatic breast cancer patients. Plasma samples and the latest available tumor tissue from 69 patients with metastatic hormone-receptor positive breast cancer were analyzed for PIK3CA hotspot mutations. A high-resolution NGS assay (SiMSen-Seq) was used for plasma samples covering 11 recurrent PIK3CA mutations, used for stratification in SOLAR-1. Additionally, mFAST-SeqS was used to estimate the tumor fractions in the plasma samples. For tumor tissue samples, targeted Ion Torrent NGS was employed. Matched tissue and plasma samples were available from 63 patients. PIK3CA mutations were detected in 46.1% of the tissue samples and in 50.7% of the plasma samples. The variant allele frequency (VAF) ranged from 4.36% to 72.93% with a median of 28.60% in tissue samples, and from 0.28% to 49.85% with a median of 1.17% in plasma samples. The most frequent variants in tissue and plasma were H1047R, E545K, and E542K. We detected at least one of 11 PIK3CA mutations from the SOLAR-1 trial in 51/63 patients, both in tissue and plasma. In 7 patients, such mutations were found only in plasma. In 5 patients, PIK3CA mutations found in tissue were not detectable in ctDNA, 2 of which had a low tumor fraction.Together, in 33/67 plasma samples without detectable PIK3CA mutations, 18 samples had elevated tumor fraction, implicating true negative results. In the remaining 15 patients with low tumor fraction, additional tissue analysis was needed. SiMSen-Seq-based detection of PIK3CA mutations in plasma shows advantageous concordance with the tissue analyses. A combination with an untargeted, mutation-independent approach for detecting ctDNA fractions may confirm a negative PIK3CA result and thereby enhance the performance of the SiMSen-Seq test. This combinatory approach for selecting suitable patients for alpelisib treatment should be validated in larger patient cohorts.","abstract":"Over the last years, the treatment of hormone receptor-positive metastatic breast cancer patients has dramatically changed. Combination strategies attempting to overcome resistance to endocrine therapy such as targeting the PI3 kinase pathway are gaining importance. The phase III SOLAR-1 trial demonstrated the benefit of the addition of alpelisib to fulvestrant, thereby providing further clinical evidence of the increasing importance of PIK3CA testing. Here, we performed a comparison of liquid biopsy and tissue-based detection of PIK3CA mutations in HR-positive metastatic breast cancer patients. Plasma samples and the latest available tumor tissue from 69 patients with metastatic hormone-receptor positive breast cancer were analyzed for PIK3CA hotspot mutations. A high-resolution NGS assay (SiMSen-Seq) was used for plasma samples covering 11 recurrent PIK3CA mutations, used for stratification in SOLAR-1. Additionally, mFAST-SeqS was used to estimate the tumor fractions in the plasma samples. For tumor tissue samples, targeted Ion Torrent NGS was employed. Matched tissue and plasma samples were available from 63 patients. PIK3CA mutations were detected in 46.1% of the tissue samples and in 50.7% of the plasma samples. The variant allele frequency (VAF) ranged from 4.36% to 72.93% with a median of 28.60% in tissue samples, and from 0.28% to 49.85% with a median of 1.17% in plasma samples. The most frequent variants in tissue and plasma were H1047R, E545K, and E542K. We detected at least one of 11 PIK3CA mutations from the SOLAR-1 trial in 51/63 patients, both in tissue and plasma. In 7 patients, such mutations were found only in plasma. In 5 patients, PIK3CA mutations found in tissue were not detectable in ctDNA, 2 of which had a low tumor fraction.Together, in 33/67 plasma samples without detectable PIK3CA mutations, 18 samples had elevated tumor fraction, implicating true negative results. In the remaining 15 patients with low tumor fraction, additional tissue analysis was needed. SiMSen-Seq-based detection of PIK3CA mutations in plasma shows advantageous concordance with the tissue analyses. A combination with an untargeted, mutation-independent approach for detecting ctDNA fractions may confirm a negative PIK3CA result and thereby enhance the performance of the SiMSen-Seq test. This combinatory approach for selecting suitable patients for alpelisib treatment should be validated in larger patient cohorts.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-06T13:31:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004941","title":"Genomic insights into the pathogenesis of Epstein-Barr virus-associated diffuse large B-cell lymphoma by whole-genome and targeted amplicon-based sequencing","description":"Epstein–Barr virus (EBV)-associated diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) constitutes a distinct clinicopathological entity in the current World Health Organization (WHO) classification, yet its genomic features remain sparsely characterized. \nCombining whole-genome sequencing (WGS), targeted amplicon sequencing (tNGS) and fluorescence in-situ hybridization (FISH) of tumours from 47 cases of EBV+ DLBCL we delineate the genomic landscape of this rare disease.\nInterrogating WGS data by sequential gene-set enrichment and network-diffusion we describe an accumulation of mutations affecting the nuclear factor κB (NFκB) pathway (CSNK2A2, CARD10), IL-6/JAK/STAT (SOCS1/3, STAT3) and WNT signalling (FRAT1, SFRP5) alongside aberrations in immunological processes like interferon-response. Further, WGS uncovered structural aberrations including 6q deletions (5/8 patients), which were subsequently validated by FISH (14/32 cases). Integrated WGS and tNGS analysis emphasized a profile distinct from EBV-negative DLBCL enriched for mutations in ARID1A (45%), KMT2A/D (32/30%), ANKRD11 (32%), NOTCH2 (32%). Expanding on previous reports, we identified recurrent alterations in CCR6 (15%), DAPK1 (15%), TNFRSF21 (13%), CCR7 (11%) and YY1 (6%). \nOur comprehensive description of the mutational landscape in EBV+ DLBCL substantiates the evidence of its pathobiological independence. Further, these observations aid in the refinement of the molecular taxonomy for aggressive lymphomas and guides future therapeutic strategies.","abstract":"Epstein–Barr virus (EBV)-associated diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) constitutes a distinct clinicopathological entity in the current World Health Organization (WHO) classification, yet its genomic features remain sparsely characterized. \nCombining whole-genome sequencing (WGS), targeted amplicon sequencing (tNGS) and fluorescence in-situ hybridization (FISH) of tumours from 47 cases of EBV+ DLBCL we delineate the genomic landscape of this rare disease.\nInterrogating WGS data by sequential gene-set enrichment and network-diffusion we describe an accumulation of mutations affecting the nuclear factor κB (NFκB) pathway (CSNK2A2, CARD10), IL-6/JAK/STAT (SOCS1/3, STAT3) and WNT signalling (FRAT1, SFRP5) alongside aberrations in immunological processes like interferon-response. Further, WGS uncovered structural aberrations including 6q deletions (5/8 patients), which were subsequently validated by FISH (14/32 cases). Integrated WGS and tNGS analysis emphasized a profile distinct from EBV-negative DLBCL enriched for mutations in ARID1A (45%), KMT2A/D (32/30%), ANKRD11 (32%), NOTCH2 (32%). Expanding on previous reports, we identified recurrent alterations in CCR6 (15%), DAPK1 (15%), TNFRSF21 (13%), CCR7 (11%) and YY1 (6%). \nOur comprehensive description of the mutational landscape in EBV+ DLBCL substantiates the evidence of its pathobiological independence. Further, these observations aid in the refinement of the molecular taxonomy for aggressive lymphomas and guides future therapeutic strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-06T14:00:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004942","title":"Multi-institutional collaboration to characterize 5hmC in prostate cancer, both tumor biopsies and cfDNA.","description":"This study used pull-down sequencing to measure 5-hydroxymethylcytosine (5hmC) levels in tissue biopsy specimens from patients with localized and metastatic castration-resistant (mCRPC) prostate cancer. For a subset of the cohort, the same technique was used to sequence cell-free DNA (cfDNA) isolated from patient plasma. To assess\n5hmC levels in cfDNA from a larger number of specimens, plasma samples from another mCRPC cohort were also assayed with this method. The larger cohort of cfDNA samples was further anlayzed with a targeted sequencing gene panel.","abstract":"This study used pull-down sequencing to measure 5-hydroxymethylcytosine (5hmC) levels in tissue biopsy specimens from patients with localized and metastatic castration-resistant (mCRPC) prostate cancer. For a subset of the cohort, the same technique was used to sequence cell-free DNA (cfDNA) isolated from patient plasma. To assess\n5hmC levels in cfDNA from a larger number of specimens, plasma samples from another mCRPC cohort were also assayed with this method. The larger cohort of cfDNA samples was further anlayzed with a targeted sequencing gene panel.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-06T17:47:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004943","title":"Single-cell RNA sequencing reveals the mesangial identity and species diversity of glomerular cell transcriptomes","description":"Molecular characterization of the individual cell types in human kidney as well as model organisms are critical in defining organ function and understanding translational aspects of biomedical research. Previous studies have uncovered gene expression profiles of several kidney glomerular cell types, however, important cells, including mesangial (MCs) and glomerular parietal epithelial cells (PECs), were missing or incompletely described, and a systematic comparison between mouse and human kidney is lacking. To this end, we used Smart-seq2 to profile 4332 individual glomerulus-associated cells isolated from human living donor renal biopsies and mouse kidney. The analysis revealed genetic programs for all four glomerular cell types (podocytes, glomerular endothelial cells, MCs and PECs) as well as rare glomerulus-associated macula densa cells (MDCs). Importantly, we detected heterogeneity in glomerulus-associated Pdgfrb-expressing cells, including bona fide intraglomerular MCs with the functionally active phagocytic molecular machinery, as well as a unique mural cell type located in the central stalk region of the glomerulus tuft. Furthermore, we observed remarkable species differences in the individual gene expression profiles of defined glomerular cell types that highlight translational challenges in the field and provide a guide to design translational studies.","abstract":"Molecular characterization of the individual cell types in human kidney as well as model organisms are critical in defining organ function and understanding translational aspects of biomedical research. Previous studies have uncovered gene expression profiles of several kidney glomerular cell types, however, important cells, including mesangial (MCs) and glomerular parietal epithelial cells (PECs), were missing or incompletely described, and a systematic comparison between mouse and human kidney is lacking. To this end, we used Smart-seq2 to profile 4332 individual glomerulus-associated cells isolated from human living donor renal biopsies and mouse kidney. The analysis revealed genetic programs for all four glomerular cell types (podocytes, glomerular endothelial cells, MCs and PECs) as well as rare glomerulus-associated macula densa cells (MDCs). Importantly, we detected heterogeneity in glomerulus-associated Pdgfrb-expressing cells, including bona fide intraglomerular MCs with the functionally active phagocytic molecular machinery, as well as a unique mural cell type located in the central stalk region of the glomerulus tuft. Furthermore, we observed remarkable species differences in the individual gene expression profiles of defined glomerular cell types that highlight translational challenges in the field and provide a guide to design translational studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-06T23:23:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004944","title":"Fasting-mimicking diet reshapes antitumor immunity in cancer patients","description":null,"abstract":"To investigate whether the fasting-mimicking diet (FMD) affects intratumor immunity, we assessed the impact of one FMD cycle before surgery in matched tumor tissue specimens from 22 early-stage breast cancer patients. At the tumor level, FMD activated antitumor immune programs in early-stage breast cancer patients.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-07T13:46:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004945","title":"A de novo paradigm for male infertility","description":null,"abstract":"De novo mutations (DNMs) arise spontaneously during gametogenesis and are known to play a prominent role in sporadic disorders with reduced fitness and genetic heterogeneity. Due to this strong effect on fitness, we hypothesize that DNMs may play a prominent role in severe forms of male infertility. In this study, we performed a unique trio-based exome sequencing study in a cohort of 185 males with azoospermia or severe oligozoospermia and their unaffected parents. We identified a total of 145 protein altering DNMs and two de novo copy number variations. A total of 29 DNMs were classified as possibly causative for the male infertility phenotype based on mutation impact and gene function. We observed a significant enrichment of Loss of function (LoF) DNMs in LoF-intolerant genes as well as of predicted pathogenic missense DNMs in missense intolerant genes. We also identified a significant enrichment in protein interactions amongst the genes affected by predicted pathogenic DNMs, in particular involving proteins involved in RNA binding and mRNA splicing. Our results provide the first support for an important role of autosomal and X-linked DNMs in the origin of severe male infertility.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004946","title":"Endothelium-derived stromal cells contribute to bone marrow niche formation","description":"Comprehensive transcriptional characterization of bone marrow stromal cells by RNA sequencing was performed to determine the molecular properties/signatures of endothelium during niche formation.Here, we identify a rare subset of cells in the human fetal BM that co-express endothelial and stromal markers, including low-affinity nerve growth factor receptor (LNGFR/CD271). They display transcriptional reprogramming consistent with endothelial-to-mesenchymal transition (EndoMT), reflected in their potential to generate stromal cells with in vivo BM niche forming capacity.","abstract":"Comprehensive transcriptional characterization of bone marrow stromal cells by RNA sequencing was performed to determine the molecular properties/signatures of endothelium during niche formation.Here, we identify a rare subset of cells in the human fetal BM that co-express endothelial and stromal markers, including low-affinity nerve growth factor receptor (LNGFR/CD271). They display transcriptional reprogramming consistent with endothelial-to-mesenchymal transition (EndoMT), reflected in their potential to generate stromal cells with in vivo BM niche forming capacity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-09T10:24:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004947","title":"Genetic insights into the biological mechanisms governing human ovarian ageing","description":"Reproductive longevity is critical for fertility and impacts healthy ageing in women, yet insights into the underlying biological mechanisms and treatments to preserve it are limited. Here, we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in ~200,000 women of European ancestry. These common alleles influence clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations. Identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increase fertility and extend reproductive life in mice. Causal inference analyses using the identified genetic variants indicates that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases risks of hormone-sensitive cancers. These findings provide insight into the mechanisms governing ovarian ageing, when they act across the life-course, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.","abstract":"Reproductive longevity is critical for fertility and impacts healthy ageing in women, yet insights into the underlying biological mechanisms and treatments to preserve it are limited. Here, we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in ~200,000 women of European ancestry. These common alleles influence clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations. Identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increase fertility and extend reproductive life in mice. Causal inference analyses using the identified genetic variants indicates that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases risks of hormone-sensitive cancers. These findings provide insight into the mechanisms governing ovarian ageing, when they act across the life-course, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-11T11:51:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004948","title":"BCR Signaling in human BM PC","description":"The functions of bone marrow plasma cells (BMPC) beyond antibody production are not fully elucidated and distinct subsets of BMPC suggest potential different functions. Phenotypic differences were identified for human BMPC depending on CD19 expression. Since CD19 is a co-stimulatory molecule of the B-cell-receptor (BCR), and IgA+ and IgM+ BMPC express the BCR on their surface, we here studied whether CD19 expression affects cellular responses, such as BCR signaling and the expression of checkpoint molecules. We analyzed 132 BM samples from individuals undergoing routine total hip arthroplasty. We found that both CD19+ and CD19- BMPC expressed BCR signaling molecules. Notably, the BCR-associated kinase spleen tyrosine kinase (SYK) including pSYK was higher expressed in CD19+BMPC compared to CD19- BMPC. BCR stimulation also resulted in increased kinase phosphorylation downstream of the BCR while expression of CD19 remained stable afterwards. Interestingly, the BCR response was restricted to IgA+ BMPC independently of CD19 expression. With regard to the expression of checkpoint molecules, CD19- BMPC expressed higher levels of co-inhibitory molecule programmed cell death protein-1 (PD-1) than CD19+ BMPC. IgA+ BMPC characteristically upregulated PD-1 upon BCR stimulation in contrast to other PC subsets and inhibition of the kinase SYK abrogated PD-1 upregulation. In contrast, expression of PD-1 ligand, B and T lymphocyte attenuator (BTLA) and CD28 did not change upon BCR activation of IgA+ BMPC. Here, we identify a distinct functiotype of IgA+ BMPC that is independent of the phenotypic heterogeneity of the subsets according to their CD19 expression. The data suggest that IgA+ BMPC underlie different regulatory principles and/or exert distinct regulatory functions.","abstract":"The functions of bone marrow plasma cells (BMPC) beyond antibody production are not fully elucidated and distinct subsets of BMPC suggest potential different functions. Phenotypic differences were identified for human BMPC depending on CD19 expression. Since CD19 is a co-stimulatory molecule of the B-cell-receptor (BCR), and IgA+ and IgM+ BMPC express the BCR on their surface, we here studied whether CD19 expression affects cellular responses, such as BCR signaling and the expression of checkpoint molecules. We analyzed 132 BM samples from individuals undergoing routine total hip arthroplasty. We found that both CD19+ and CD19- BMPC expressed BCR signaling molecules. Notably, the BCR-associated kinase spleen tyrosine kinase (SYK) including pSYK was higher expressed in CD19+BMPC compared to CD19- BMPC. BCR stimulation also resulted in increased kinase phosphorylation downstream of the BCR while expression of CD19 remained stable afterwards. Interestingly, the BCR response was restricted to IgA+ BMPC independently of CD19 expression. With regard to the expression of checkpoint molecules, CD19- BMPC expressed higher levels of co-inhibitory molecule programmed cell death protein-1 (PD-1) than CD19+ BMPC. IgA+ BMPC characteristically upregulated PD-1 upon BCR stimulation in contrast to other PC subsets and inhibition of the kinase SYK abrogated PD-1 upregulation. In contrast, expression of PD-1 ligand, B and T lymphocyte attenuator (BTLA) and CD28 did not change upon BCR activation of IgA+ BMPC. Here, we identify a distinct functiotype of IgA+ BMPC that is independent of the phenotypic heterogeneity of the subsets according to their CD19 expression. The data suggest that IgA+ BMPC underlie different regulatory principles and/or exert distinct regulatory functions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-11T12:22:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004949","title":"Comparison of the diagnostic yield of aCGH and NGS across different neurodevelopmental disorders","description":"Current recommendations for the genetic diagnosis of neurodevelopmental disorders (NDDs) do not include the use of next generation sequencing (NGS) and are still based on chromosomal microarrays, such as comparative genomic hybridization array (aCGH). The present study compares the diagnostic yield obtained by aCGH and clinical exome sequencing in NDD globally and its spectrum of disorders. To that end, 1412 patients clinically diagnosed with NDDs and studied with aCGH were classified into phenotype categories: Global developmental delay/intellectual disability (GDD/ID); autism spectrum disorder (ASD); and Other NDDs. These categories were further subclassified into subcategories, based on the most frequent accompanying signs and symptoms: isolated forms, forms with epilepsy; forms with micro or macrocephaly and syndromic forms. A subset of 245 patients of the 1412 were subjected to clinical exome sequencing. Diagnostic yield of aCGH and clinical exome sequencing, expressed as the number of solved cases, was compared for each phenotype category and subcategory. Clinical exome sequencing was superior than aCGH for all cases except for isolated ASD, with no cases solved by NGS. Globally, clinical exome sequencing solved 20% of cases (versus 5.7% by aCGH) and the diagnostic yield was highest for all forms of GDD/ID and lowest for Other NDDs (7.1% versus 1.4% by aCGH) and ASD (6.1% versus 3% by aCGH). In the majority of cases, diagnostic yield was higher in the phenotype subcategories than in the mother category. These results support the use of NGS as the first-tier test in the diagnostic algorithm of all NDDs followed by aCGH when necessary.","abstract":"Current recommendations for the genetic diagnosis of neurodevelopmental disorders (NDDs) do not include the use of next generation sequencing (NGS) and are still based on chromosomal microarrays, such as comparative genomic hybridization array (aCGH). The present study compares the diagnostic yield obtained by aCGH and clinical exome sequencing in NDD globally and its spectrum of disorders. To that end, 1412 patients clinically diagnosed with NDDs and studied with aCGH were classified into phenotype categories: Global developmental delay/intellectual disability (GDD/ID); autism spectrum disorder (ASD); and Other NDDs. These categories were further subclassified into subcategories, based on the most frequent accompanying signs and symptoms: isolated forms, forms with epilepsy; forms with micro or macrocephaly and syndromic forms. A subset of 245 patients of the 1412 were subjected to clinical exome sequencing. Diagnostic yield of aCGH and clinical exome sequencing, expressed as the number of solved cases, was compared for each phenotype category and subcategory. Clinical exome sequencing was superior than aCGH for all cases except for isolated ASD, with no cases solved by NGS. Globally, clinical exome sequencing solved 20% of cases (versus 5.7% by aCGH) and the diagnostic yield was highest for all forms of GDD/ID and lowest for Other NDDs (7.1% versus 1.4% by aCGH) and ASD (6.1% versus 3% by aCGH). In the majority of cases, diagnostic yield was higher in the phenotype subcategories than in the mother category. These results support the use of NGS as the first-tier test in the diagnostic algorithm of all NDDs followed by aCGH when necessary.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-11T15:10:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004950","title":"CASCADE metastatic melanoma study","description":"In this study we analyse the evolution of human melanoma from early to late disease in patients by sampling their tumours at multiple sites and times. Whole exome and genome sequencing data from tumour samples reveals only limited gain of point mutations generally, with net mutational loss in some metastases. In contrast, melanoma evolution is dominated by whole genome doubling and large-scale aneuploidy, in which widespread loss of heterozygosity sculpts the burden of point mutations, neoantigens and structural variants even in treatment-naïve and primary cutaneous melanomas in some patients. These results imply that dysregulation of genomic integrity is a key driver of selective clonal advantage during melanoma progression.","abstract":"In this study we analyse the evolution of human melanoma from early to late disease in patients by sampling their tumours at multiple sites and times. Whole exome and genome sequencing data from tumour samples reveals only limited gain of point mutations generally, with net mutational loss in some metastases. In contrast, melanoma evolution is dominated by whole genome doubling and large-scale aneuploidy, in which widespread loss of heterozygosity sculpts the burden of point mutations, neoantigens and structural variants even in treatment-naïve and primary cutaneous melanomas in some patients. These results imply that dysregulation of genomic integrity is a key driver of selective clonal advantage during melanoma progression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-12T05:34:18+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004951","title":"Upper respiratory microbiome of COVID-19 patients","description":"Understanding the pathology of COVID-19 is a global research priority. Early evidence suggests that the microbiome may be playing a role in disease progression, yet current studies report contradictory results. Here, we examine potential confounders in COVID-19 microbiome studies by analyzing the upper respiratory tract microbiome in well-phenotyped COVID-19 patients and controls combining microbiome sequencing, viral load determination, and immunoprofiling. We found that time in the intensive care unit and the type of oxygen support explained the most variation within the upper respiratory tract microbiome, dwarfing (non-significant) effects from viral load, disease severity, and immune status. Specifically, mechanical ventilation was linked to altered community structure, lower species- and higher strain-level diversity, and significant shifts in oral taxa previously associated with COVID-19.","abstract":"Understanding the pathology of COVID-19 is a global research priority. Early evidence suggests that the microbiome may be playing a role in disease progression, yet current studies report contradictory results. Here, we examine potential confounders in COVID-19 microbiome studies by analyzing the upper respiratory tract microbiome in well-phenotyped COVID-19 patients and controls combining microbiome sequencing, viral load determination, and immunoprofiling. We found that time in the intensive care unit and the type of oxygen support explained the most variation within the upper respiratory tract microbiome, dwarfing (non-significant) effects from viral load, disease severity, and immune status. Specifically, mechanical ventilation was linked to altered community structure, lower species- and higher strain-level diversity, and significant shifts in oral taxa previously associated with COVID-19.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-12T08:09:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004952","title":"Visium","description":"We will combine state-of-the-art 10x visium data generation with single cell experimental data to spatially map the transcriptome on our tissues. We anticipate that the results will enable us to characterise cell-cell interactions as well as validate target gene upregulations and downregulations in our specific tissue samples","abstract":"New spatial transcriptomics/genomics (STx) technologies promise to provide unprecedented insight into the mechanisms of tissue and cell-to-cell control in health and disease, because the underlying molecular changes can be measured in situ. This has several advantages over single-cell RNA sequencing (scRNA-seq) as the spatial localisation enables to identify which cells interact and which parts of the tissue are involved. However, reliably quantifying these changes of cell states requires the development of novel methodologies, combining computer vision, high-dimensional statistical methods of scRNA-seq data analysis and spatial statistics","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004953","title":"The temporal mutational and immune tumour microenvironment remodelling of HER2-negative primary breast cancers","description":"WES and clonality characterization of different timepoints in HER2-negative primary breast cancers receiving neoadjuvant eribulin therapy.","abstract":"WES and clonality characterization of different timepoints in HER2-negative primary breast cancers receiving neoadjuvant eribulin therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-13T09:00:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004954","title":"test","description":null,"abstract":"testtest","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004955","title":"Single-nuclei RNAseq of normal human choroid and uveal melanoma","description":"Single-nuclei RNAseq of normal human choroid and uveal melanoma","abstract":"The normal counterparts of choroidal uveal melanoma cells are the melanocytes residing in choroid layer of the eye. The absence of reliable melanocytic cell surface markers prevents direct sorting of live cells with a simple staining method. In addition, melanin absorbs more efficiently light at the UV-Violet range, and in contrast it autofluoresces at the red-near infrared range. This presents unique challenges for the isolation of melanocytes by flow cytometry, which prevents comparison of transcriptomic profiles of normal choroid melanocytes versus uveal melanoma.\nUsing single-nuclei RNAseq on cell suspensions of normal choroid samples obtained from enucleation surgeries at Institut Curie, we have shown that melanocytes comprise up to 20% of the cells. The remaining cells comprised of a complex combination of fibroblasts, leukocytes, schwann-like cell, endothelial cells, photoreceptors and retinal pigment epithelium cells. We harnessed this resource for comparing the expression of key oncogenes in melanocytes versus matched melanomas","study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-25T14:17:04.988891+02:00","is_deprecated":false},
{"accession_id":"EGAS00001004956","title":"Converging and evolving immuno-genomic routes towards immune escape in breast cancer","description":"This study explores the evolution of tumor and blood immune microenvironment and related mechanisms that shape breast cancer progression, culminating in a heterogeneous lethal cancer.","abstract":"This study explores the evolution of tumor and blood immune microenvironment and related mechanisms that shapes breast cancer progression, culminating in a heterogeneous lethal cancer.","study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-17T17:49:32.701177+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004957","title":"MutWPX__CRUK_Grand_Challenge_Mutographs_of_Cancer__Effects_of_Chemotherapy_on_the_Somatic_Mutational_Landscape_in_Normal_Human_Tissue___Matched_Normals","description":"This study is investigating the effects of chemotherapy drugs used in cancer treatment on the somatic mutational landscape in normal human tissues. The samples used in this study have been taken from rapid autopsies of patients who have undergone chemotherapy using drugs thought to cause mutations in the DNA. Structures from a variety of tissues will be dissected using LCM and whole genome sequences will be produced in order to assess mutational burdens and signatures.  This study contains the samples used as matched normals for each patient to remove germline mutations.","abstract":"This study is investigating the effects of chemotherapy drugs used in cancer treatment on the somatic mutational landscape in normal human tissues. The samples used in this study have been taken from rapid autopsies of patients who have undergone chemotherapy using drugs thought to cause mutations in the DNA. Structures from a variety of tissues will be dissected using LCM and whole genome sequences will be produced in order to assess mutational burdens and signatures. This study contains the samples used as matched normals for each patient to remove germline mutations.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-14T14:47:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004958","title":"Sperm_PacBio_CCS_sequencing","description":"PacBio circular consensus sequencing (CCS) produces long reads with unparalleled base accuracy. Longer read length enables confident placement of reads to the reference genome and this allows nucleotide resolution detection of structural rearrangements. Our internal assessment of PacBio CCS base accuracy shows that PacBio CCS reads can be used for single molecule somatic mutation detection. We will take advantage of these PacBio CCS read properties to attempt single molecule meiotic recombination and gene conversion detection and define meiotic recombination and gene conversion rate. In addition, we will be able to use the single molecule somatic mutation detection method to screen for pathogenic de novo mutations. In the pilot phase, we will be sequencing sperm samples from three different individuals to determine the individual and age effect on meiotic recombination and gene conversion rate.","abstract":"ere, we will be using PacBio CCS reads to attempt single molecule meiotic recombination and gene conversion detection across sperm samples to determine the age and individual effect on meiotic recombination and gene conversion rate.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-14T15:00:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004959","title":"GCP study","description":null,"abstract":"Genome sequencing data of gastric cancer with peritoneal metastasis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-14T17:51:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004960","title":"Sequencing of cell-free DNA from breast cancer patients","description":"To assess the utility of high coverage whole genome sequencing analysis of cell-free DNA to detect tumour-specific genomic changes","abstract":"To assess the utility of high coverage whole genome sequencing analysis of cell-free DNA to detect tumour-specific genomic changes","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-15T04:16:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004961","title":"Copy number and mutation profiling of Stage 1 epithelial ovarian cancer biopsies","description":"This project aims at characterizing the genome-wide copy number profile and the variant profile of 139 genes om the five major histotytpes of early-stage (stage I) epithelial ovarian cancer (EOC), to provide insight in the the aethiology and development of the disease.","abstract":"This project aims at characterizing the genome-wide copy number profile and the variant profile of 139 genes om the five major histotytpes of early-stage (stage I) epithelial ovarian cancer (EOC), to provide insight in the the aethiology and development of the disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-15T13:44:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004962","title":"Cell-free DNA TAPS for early cancer detection","description":"Multimodal, genome-wide characterization of epigenetic and genetic information in circulating cell-free DNA (cfDNA) could enable more sensitive early cancer detection. However, due to technological challenges associated with DNA methylation sequencing in low input cfDNA samples, most studies have been limited by DNA damage caused by bisulfite sequencing, or the qualitative nature of enrichment-based sequencing. Recently, we developed TET-assisted Pyridine Borane Sequencing (TAPS), which is a mild, bisulfite-free method for base-resolution direct DNA methylation sequencing. Here we optimized TAPS for cfDNA (cfTAPS) to provide high-quality and high-depth whole-genome cell-free methylomes. We applied cfTAPS to 85 cfDNA samples from patients with hepatocellular carcinoma (HCC) or pancreatic ductal adenocarcinoma (PDAC) and non-cancer controls. From just 10 ng cfDNA (1-3 mL of plasma), we generated the most comprehensive cfDNA methylome to date. We demonstrated that cfTAPS provides multimodal information about cfDNA characteristics, including DNA methylation, tissue of origin, and DNA fragmentation. Integrated analysis of these epigenetic and genetic features enables accurate identification of early HCC and PDAC.","abstract":"Multimodal, genome-wide characterization of epigenetic and genetic information in circulating cell-free DNA (cfDNA) could enable more sensitive early cancer detection. However, due to technological challenges associated with DNA methylation sequencing in low input cfDNA samples, most studies have been limited by DNA damage caused by bisulfite sequencing, or the qualitative nature of enrichment-based sequencing. Recently, we developed TET-assisted Pyridine Borane Sequencing (TAPS), which is a mild, bisulfite-free method for base-resolution direct DNA methylation sequencing. Here we optimized TAPS for cfDNA (cfTAPS) to provide high-quality and high-depth whole-genome cell-free methylomes. We applied cfTAPS to 85 cfDNA samples from patients with hepatocellular carcinoma (HCC) or pancreatic ductal adenocarcinoma (PDAC) and non-cancer controls. From just 10 ng cfDNA (1-3 mL of plasma), we generated the most comprehensive cfDNA methylome to date. We demonstrated that cfTAPS provides multimodal information about cfDNA characteristics, including DNA methylation, tissue of origin, and DNA fragmentation. Integrated analysis of these epigenetic and genetic features enables accurate identification of early HCC and PDAC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-15T14:33:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004963","title":"Assessment of cannabidiol and Δ9-tetrahydrocannabiol in mouse models of medulloblastoma","description":"Phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have been demonstrated to exhibit anti-cancer activity in preclinical models of brain cancer leading to new clinical trials for adults with glioblastoma. We describe here the first report that has investigated a role for THC and CBD in paediatric brain cancer. Cannabinoids had cytotoxic activity against medulloblastoma and ependymoma cells in vitro, functioning in part through the inhibition of cell cycle progression and the induction of autophagy. Despite these effects in vitro, when tested in orthotopic mouse models of medulloblastoma or ependymoma, no impact on animal survival was observed. Furthermore, cannabinoids neither enhanced nor impaired conventional chemotherapy in a medulloblastoma mouse model. These data show that while THC and CBD do have some effects on medulloblastoma and ependymoma cells, are well tolerated and have minimal adverse effects, they do not appear to elicit any survival benefit in preclinical models of paediatric brain cancer.","abstract":"Phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have been demonstrated to exhibit anti-cancer activity in preclinical models of brain cancer leading to new clinical trials for adults with glioblastoma. We describe here the first report that has investigated a role for THC and CBD in paediatric brain cancer. Cannabinoids had cytotoxic activity against medulloblastoma and ependymoma cells in vitro, functioning in part through the inhibition of cell cycle progression and the induction of autophagy. Despite these effects in vitro, when tested in orthotopic mouse models of medulloblastoma or ependymoma, no impact on animal survival was observed. Furthermore, cannabinoids neither enhanced nor impaired conventional chemotherapy in a medulloblastoma mouse model. These data show that while THC and CBD do have some effects on medulloblastoma and ependymoma cells, are well tolerated and have minimal adverse effects, they do not appear to elicit any survival benefit in preclinical models of paediatric brain cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-16T09:02:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004964","title":"Preliminary Results from the Initiative for Molecular Profiling and Advanced Cancer Therapy 2 (IMPACT 2) Study","description":null,"abstract":"Precision medicine is associated with favorable outcomes in selected patients with cancer. Herein, we report an interim analysis of IMPACT2, an ongoing randomized study evaluating genomic profiling and targeted agents in metastatic cancer. Patients with metastatic cancer underwent tumor genomic profiling (ClinialTrials.gov: NCT02152254), and 69 patients met the criteria for randomization.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-18T06:34:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004965","title":"Evaluation of capture and amplicon-based targeted sequencing methods on formalin-fixed tumours","description":"Evaluated performance of three capture (Agilent’s SureSelectXT HS, Illumina’s Nextera Rapid Capture Custom, and New England Biolabs’ Next Direct Custom) and one amplicon-based (Qiagen’s Human Breast Cancer Panel) targeted sequencing methods on paired blood and FFPE, using whole exome sequencing data from matched fresh-frozen tissue as a comparison.","abstract":"Evaluated performance of three capture (Agilent’s SureSelectXT HS, Illumina’s Nextera Rapid Capture Custom, and New England Biolabs’ Next Direct Custom) and one amplicon-based (Qiagen’s Human Breast Cancer Panel) targeted sequencing methods on paired blood and FFPE, using whole exome sequencing data from matched fresh-frozen tissue as a comparison.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-18T06:57:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004966","title":"Multiomics analyses of Parkinson's disease midbrains","description":"Understanding the key pathological mechanisms underlying Parkinson's Disease pathology is fundamental for the development of novel and more effective therapeutic strategies. In this study, post-mortem human midbrain tissue from a cohort of 13 PD patients and 10 controls was analyzed with a set of multi-omics technologies including small RNA sequencing, transcriptomics and proteomics profiling.","abstract":"Understanding the key pathological mechanisms underlying Parkinson's Disease pathology is fundamental for the development of novel and more effective therapeutic strategies. In this study, post-mortem human midbrain tissue from a cohort of 13 PD patients and 10 controls was analyzed with a set of multi-omics technologies including small RNA sequencing, transcriptomics and proteomics profiling.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-18T17:57:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004967","title":"Transcriptomic analysis of TFEB knockdown in LT-HSC.","description":"Long-term hematopoietic stem cells (LT-HSC) were sorted from human cord blood and cultured overnight before transduction with lentiviral vectors overexpressing an shRNA against Renilla (shCTRL) or TFEB (shTFEB). Six days later, mCherry+ transduced cells were sorted for RNA extraction and sequencing.","abstract":"Long-term hematopoietic stem cells (LT-HSC) were sorted from human cord blood and cultured overnight before transduction with lentiviral vectors overexpressing an shRNA against Renilla (shCTRL) or TFEB (shTFEB). Six days later, mCherry+ transduced cells were sorted for RNA extraction and sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-18T18:15:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004968","title":"Transcriptomic analysis of human hematopoietic populations sorted from umbilical cord blood.","description":"We isolated by fluorescence-activated cell sorting highly purified populations (long term hematopoietic stem cells (LT-HSCs), short term hematopoietic stem cells (ST-HSCs), multipotent progenitors (MPPs), common myeloid progenitor (CMPs), granulocyte and monocyte progenitors (GMPs), multilymphoid progenitors (MLPs), Myeloid-erythorid Progenitor (MEP), Granulocytes, Monocytes, B cells, T cells, Dendritic cells, Natural Killer cells and Erythrocyte Progenitors from 3 to 4 cord blood pools. We extracted RNA from 5K cells of each population and performed RNA-sequencing.","abstract":"We isolated by fluorescence-activated cell sorting highly purified populations (long term hematopoietic stem cells (LT-HSCs), short term hematopoietic stem cells (ST-HSCs), multipotent progenitors (MPPs), common myeloid progenitor (CMPs), granulocyte and monocyte progenitors (GMPs), multilymphoid progenitors (MLPs), Myeloid-erythorid Progenitor (MEP), Granulocytes, Monocytes, B cells, T cells, Dendritic cells, Natural Killer cells and Erythrocyte Progenitors from 3 to 4 cord blood pools. We extracted RNA from 5K cells of each population and performed RNA-sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-18T18:15:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004969","title":"Transcriptomic analysis of TFEB overexpression in LT-HSC, ST-HSC and MEP","description":"Long-term hematopoietic stem cells (LT-HSC), Short-term hematopietic stem cells (ST-HSC) and Megakaryocyte-erythrocyte progenitors (MEP) were sorted from human cord blood and cultured overnight before transduction with lentivirus to overexpress GP91 (CTRL) or TFEB. Three (LT-HSC ans ST-HSC) or six (MEP) days later, BFP+ transduced cells were sorted for RNA extraction and sequencing.","abstract":"Long-term hematopoietic stem cells (LT-HSC), Short-term hematopietic stem cells (ST-HSC) and Megakaryocyte-erythrocyte progenitors (MEP) were sorted from human cord blood and cultured overnight before transduction with lentivirus to overexpress GP91 (CTRL) or TFEB. Three (LT-HSC ans ST-HSC) or six (MEP) days later, BFP+ transduced cells were sorted for RNA extraction and sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-18T18:15:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004970","title":"Transcriptomic analysis of MYC overexpression in LT-HSC.","description":"Long-term hematopoietic stem cells (LT-HSC) were sorted from human cord blood and cultured overnight before transduction with lentiviral vectors (empty E CTRL or MYC). Six days after transduction, BFP+ transduced cells were sorted for RNA extraction and sequencing","abstract":"Long-term hematopoietic stem cells (LT-HSC) were sorted from human cord blood and cultured overnight before transduction with lentiviral vectors (empty E CTRL or MYC). Six days after transduction, BFP+ transduced cells were sorted for RNA extraction and sequencing","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-18T18:15:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004971","title":"Chromatin accessibility analysis of TFEB overexpression in LT-HSC","description":"Long-term hematopoietic stem cells (LT-HSC) were sorted from human cord blood and cultured overnight before transduction with lentivirus overexpressing GP91 (CTRL) or TFEB. Six days later, BFP+ transduced cells were sorted for DNA extraction, library preparation and sequencing","abstract":"Long-term hematopoietic stem cells (LT-HSC) were sorted from human cord blood and cultured overnight before transduction with lentivirus overexpressing GP91 (CTRL) or TFEB. Six days later, BFP+ transduced cells were sorted for DNA extraction, library preparation and sequencing","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-18T18:15:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004972","title":"Sensitive and robust liquid biopsy-based detection of PIK3CA mutations in hormone-receptor positive metastatic breast cancer patients","description":"Over the last years, the treatment of hormone receptor-positive metastatic breast cancer patients has dramatically changed. Combination strategies attempting to overcome resistance to endocrine therapy such as targeting the PI3 kinase pathway are gaining importance. The phase III SOLAR-1 trial demonstrated the benefit of the addition of alpelisib to fulvestrant, thereby providing further clinical evidence of the increasing importance of PIK3CA testing. Here, we performed a comparison of liquid biopsy and tissue-based detection of PIK3CA mutations in HR-positive metastatic breast cancer patients. Plasma samples and the latest available tumor tissue from 69 patients with metastatic hormone-receptor positive breast cancer were analyzed for PIK3CA hotspot mutations. A high-resolution NGS assay (SiMSen-Seq) was used for plasma samples covering 11 recurrent PIK3CA mutations, used for stratification in SOLAR-1. Additionally, mFAST-SeqS was used to estimate the tumor fractions in the plasma samples. For tumor tissue samples, targeted Ion Torrent NGS was employed. Matched tissue and plasma samples were available from 63 patients. PIK3CA mutations were detected in 47.7% of the tissue samples and in 50.8% of the plasma samples. The variant allele frequency (VAF) ranged from 4.36% to 72.93% with a median of 28.60% in tissue samples, and from 0.28% to 49.85% with a median of 1.17% in plasma samples. The most frequent variants in tissue and plasma were H1047R, E545K, and E542K. We detected at least one of 11 PIK3CA mutations from the SOLAR-1 trial in 50/63 patients, both in tissue and plasma. In 8 patients, such mutations were found only in plasma. In 5 patients, PIK3CA mutations found in tissue were not detectable in ctDNA, 2 of which had a low tumor fraction. Together, in 33/67 plasma samples without detectable PIK3CA mutations, 18 samples had elevated tumor fraction, implicating true negative results. In the remaining 15 patients with low tumor fraction, additional tissue analysis was needed. SiMSen-Seq-based detection of PIK3CA mutations in plasma shows advantageous concordance with the tissue analyses. A combination with an untargeted, mutation-independent approach for detecting ctDNA fractions may confirm a negative PIK3CA result and thereby enhance the performance of the SiMSen-Seq test. This combinatory approach for selecting suitable patients for alpelisib treatment should be validated in larger patient cohorts.","abstract":"Over the last years, the treatment of hormone receptor-positive metastatic breast cancer patients has dramatically changed. Combination strategies attempting to overcome resistance to endocrine therapy such as targeting the PI3 kinase pathway are gaining importance. The phase III SOLAR-1 trial demonstrated the benefit of the addition of alpelisib to fulvestrant, thereby providing further clinical evidence of the increasing importance of PIK3CA testing. Here, we performed a comparison of liquid biopsy and tissue-based detection of PIK3CA mutations in HR-positive metastatic breast cancer patients. Plasma samples and the latest available tumor tissue from 69 patients with metastatic hormone-receptor positive breast cancer were analyzed for PIK3CA hotspot mutations. A high-resolution NGS assay (SiMSen-Seq) was used for plasma samples covering 11 recurrent PIK3CA mutations, used for stratification in SOLAR-1. Additionally, mFAST-SeqS was used to estimate the tumor fractions in the plasma samples. For tumor tissue samples, targeted Ion Torrent NGS was employed. Matched tissue and plasma samples were available from 63 patients. PIK3CA mutations were detected in 47.7% of the tissue samples and in 50.8% of the plasma samples. The variant allele frequency (VAF) ranged from 4.36% to 72.93% with a median of 28.60% in tissue samples, and from 0.28% to 49.85% with a median of 1.17% in plasma samples. The most frequent variants in tissue and plasma were H1047R, E545K, and E542K. We detected at least one of 11 PIK3CA mutations from the SOLAR-1 trial in 50/63 patients, both in tissue and plasma. In 8 patients, such mutations were found only in plasma. In 5 patients, PIK3CA mutations found in tissue were not detectable in ctDNA, 2 of which had a low tumor fraction. Together, in 33/67 plasma samples without detectable PIK3CA mutations, 18 samples had elevated tumor fraction, implicating true negative results. In the remaining 15 patients with low tumor fraction, additional tissue analysis was needed. SiMSen-Seq-based detection of PIK3CA mutations in plasma shows advantageous concordance with the tissue analyses. A combination with an untargeted, mutation-independent approach for detecting ctDNA fractions may confirm a negative PIK3CA result and thereby enhance the performance of the SiMSen-Seq test. This combinatory approach for selecting suitable patients for alpelisib treatment should be validated in larger patient cohorts.","study_type":"Other","pubmed_ids":[34754095],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004973","title":"Application of short-RNA-seq in post-mortem human hippocampi from the Calgary Brain Bank (CBB) to assess transcriptome-wide deregulation in processing of SINE Alu RNAs in Alzheimer’s disease","description":"Here, we investigate through short-RNA_seq in human hippocampi from the Calgary Brain Bank (CBB) whether Alu RNAs are processed in human brains,  and whether their processing ratio is deregulated in brains of AD patients compared to healthy aging individuals.","abstract":"Here, we investigate through short-RNA_seq in human hippocampi from the Calgary Brain Bank (CBB) whether Alu RNAs are processed in human brains,  and whether their processing ratio is deregulated in brains of AD patients compared to healthy aging individuals.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-19T19:32:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004974","title":"Macrophage response in preterm infants compared to term infants","description":"Preterm infants are highly susceptible to sustained lung inflammation, which may be triggered by exposure to multiple environmental cues such as supplemental oxygen (O2) and infections. The underlying mechanisms are still poorly understood. The hypothesis of this study is that dysregulated macrophage activation is a key feature leading to inflammation-mediated development of bronchopulmonary dysplasia (BPD) in preterm infants. \nCord blood samples of preterm infants (n=14) and term infants (n=19) as well as peripheral blood from healthy adults (n=17) were collected. Age-dependent differences in immune responses of monocyte-derived MФ from preterm infants were characterized and compared to term infants and adults after lipopolysaccharide (LPS) exposure.","abstract":"Preterm infants are highly susceptible to sustained lung inflammation, which may be triggered by exposure to multiple environmental cues such as supplemental oxygen (O2) and infections. The underlying mechanisms are still poorly understood. The hypothesis of this study is that dysregulated macrophage activation is a key feature leading to inflammation-mediated development of bronchopulmonary dysplasia (BPD) in preterm infants. \nCord blood samples of preterm infants (n=14) and term infants (n=19) as well as peripheral blood from healthy adults (n=17) were collected. Age-dependent differences in immune responses of monocyte-derived MФ from preterm infants were characterized and compared to term infants and adults after lipopolysaccharide (LPS) exposure.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-19T19:34:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004975","title":"Nanopore sequencing from liquid biopsy: analysis of copy number variations from cell-free DNA of lung cancer patients","description":null,"abstract":"Alterations in the genetic content, such as Copy Number Variations (CNVs) is one of the hallmarks of cancer and their detection is used to recognize tumoral DNA. Analysis of cell-free DNA from plasma is a powerful tool for non-invasive disease monitoring in cancer patients. Here we exploit third generation sequencing (Nanopore) to obtain a CNVs profile of tumoral DNA from plasma, where cancer-related chromosomal alterations are readily identifiable. Compared to Illumina sequencing -the only available alternative- Nanopore sequencing represents a viable approach to characterize the molecular phenotype, both for its ease of use, costs and rapid turnaround (6 hours).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-19T21:45:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004976","title":"Transcriptome sequencing from liver and adjacent tissue biopsies from 114 hepatocellular carcinoma patients","description":null,"abstract":"Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths and effective therapies are still needed. The search for new biomarkers and drug targets has spurred an interest in long non-coding RNAs (lncRNAs), often proposed as oncogenes or tumor suppressors. However, many recent claims regarding lncRNAs in HCC were proven controversial and warrant verification. With this aim, we examine lncRNAs in a large HCC cohort, comprising RNA-seq data from paired tumor and adjacent tissue biopsies from 114 patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004977","title":"CRISPR_Cas___scRNAseq_in_human_iPSCs","description":"This study will measure transcriptomes in undifferentiated genome edited induced pluripotent stem cells derived from multiple healthy donors. Single cells are collected after CRISPR/Cas perturbation, and single cell RNA libraries constructed using the 10x Genomics 5' kit. The guide RNAs and the transcriptome are captured simultaneously, and the gene expression and guide RNA library will be pooled together for sequencing. The first four lanes of sequencing pertain to 16 10x inlets that are used for cell populations of 150 perturbed genes in 24 cell lines, and are covered under prelim WC10264. If it is successful, additional funding will be sought for additional experiments.","abstract":"Core questions in human genetics can be addressed by measuring transcriptomes of single cells in response to genetic perturbations. Building on a successful pilot single-cell CRISPR screen, here we apply our approach at scale on pools of iPSCs from healthy donors of the HIPSCI cohort with different genetic backgrounds, targeting large sets of genes with a range of fitness effects. The outputs of these experiments are transcriptomes and guide RNA identities in single cells from these donors, which will illuminate the effect of the different genetic perturbations on gene expression. These screen are part of an effort to establish gene regulatory networks in cell fitness and differentiation, and their differences across different individuals.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004978","title":"HCA_Kidney_Adult_WSSS_Spatial","description":"Spatial cell atlas of Human adult kidney","abstract":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. This specific project will assess epigenetic and transcriptomic landscape of cells of the adult human kidney. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004979","title":"SNParray","description":"SNP array study for UTUC","abstract":"SNP array study for UTUC","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-21T07:56:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004980","title":"Dissecting_global_protective_immune_response_to_dengue_virus_at_a_single_cell_resolution","description":"1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Dengue virus (DENV) infection is a mosquito-borne disease that infects 390 million people each year. Despite a sharp rise in the number of infected case over the past decade, there is currently no available specific treatment. A vaccine has been developed but is of limited efficacy and has been shown to cause severe side-effects when given to young children. It has been observed that some individuals who are infected with the virus either develop no or very mild symptoms and clear the virus, whereas other individuals develop fever and severe symptoms such as bleeding and shock. Here we aim to compare infected individuals with and without these harmful symptoms to better understand which parts of the immune systems are responsible for clearing the virus and which parts are responsible for causing the often very severe symptoms without clearing the virus effectively. Human \"innate\" immune response reacts to general danger signals such as those generated during a viral infection, whereas the \"adaptive\" immune response recognises the shape of an invader and mount a specific response against this. B and T lymphocytes are the mediators of the adaptive immune response. Each individual T and B lymphocyte carries a unique receptor that is able to recognise a different shape on the infectious agent. Therefore, ideally, immune responses need to be studied at the level of the single cell. At the Wellcome Trust Sanger Institute (WTSI UK), cutting-edge technology has recently been developed that is able to profile immune cells at the single cell level. Complex \"transcriptomics\" data are generated, and computational tools for the successful analysis of this type of large-scale data have only recently been developed.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-21T14:27:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004981","title":"McGill Epigenomics Mapping Centre","description":null,"abstract":"The McGill Epigenomics Mapping Centre (EMC) and Data Coordination Centre (EDCC) were established in 2012 at the McGill University and Genome Quebec Innovation Centre (Montreal, Canada) to support large-scale human epigenome mapping for a broad spectrum of cell types and diseases. Previous epigenetic studies have provided profiles of specific chromatin marks in relation to basic biological processes, and future studies of molecular mechanisms must build upon these proofs-of-concept by integrating sequence-based variation with multiple levels of epigenetic and transcriptional regulation across the genome of human tissues and animal disease models. This project leverages the high-throughput sequencing infrastructure and expertise in genomics and transcriptomics at the McGill Innovation Centre to carry out this research. Controlled access to the data by collaborators and the greater scientific community is gained via a portal, which takes advantage of Compute Canada high-performance computing cluster resources to manage the large volume of data associated from the generation of reference epigenome maps. McGill University is one of two Canadian mapping and data coordination centres, the other based at the Michael Smith Genome Sciences Centre in Vancouver, British Columbia. The generation of comprehensive epigenome maps at McGill University is part of a larger international effort that is coordinated by the International Human Epigenome Consortium (IHEC), whose overall long-term objective is to determine the extent to which the epigenome shapes human populations over generations and in response to the environment. This project is funded under the Canadian Epigenetics, Environment, and Health Research Consortium (CEEHRC) by the Canadian Institutes of Health Research and by Genome Quebec, with additional support from Genome Canada. The computing and networking infrastructure, and part of the software development, are provided by Compute Canada and CANARIE.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004982","title":"Integrative Molecular Classification of Meningiomas","description":"Integrative Molecular Classification of Meningiomas","abstract":"Integrative Molecular Classification of Meningiomas","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-21T18:08:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004983","title":"Genomic and TCR Repertoire Intratumor Heterogeneity of Small-cell Lung Cancer and its Impact on Survival","description":null,"abstract":"we revealed a rather homogeneous mutational landscape but extremely cold and heterogeneous T cell receptor (TCR) repertoire in SCLC tumors. Higher mutational burden, lower chromosomal copy number aberration (CNA) burden, less CNA ITH and less TCR ITH were associated with longer overall survival of SCLC patients. Compared to non-small cell lung cancers (NSCLCs), SCLCs had similar predicted neoantigen burden and mutational ITH, but significantly more cold and heterogeneous TCR repertoire that may be associated with higher CNA burden and CNA ITH in SCLC.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004984","title":"Foetal_macrophage_development","description":"Whole-genome sequencing of single-cell derived colonies from early human foetal specimens.  These will be primarily haematopoietic stem and progenitor cell (HSPC)- and microglia-derived.\n\nThe WGS will be used to construct phylogenies of the single cells that will help determine macrophage ontogeny and migration timing.","abstract":"Macrophages play critical roles in human disease through defence, regulation and repair. Once thought to arise from monocytes, recent data indicate that they originate and renew in diverse ways. Microglia arise from primitive yolk sac progenitors and remain independent of definitive haematopoiesis. Kupffer cells and alveolar macrophages are formed by fetal liver monocytes but become independent of haematopoiesis, unless perturbed. In many tissues, notably skin and gut, both long-lived primitive origin and recently recruited haematogenous macrophages can be found; their origin and mode of homeostasis linked to profound functional differences. We and others have shown that parallels exist in humans, using transplantation and genetic deficiency. However, these are perturbed states, populations such as microglia are difficult to access, and the potential founding role of the human yolk sac has not been interrogated. \nThe synchronous development of resident macrophages within tissues initiates homeostatic mechanisms that maintain tolerance, vascular integrity, neuronal health, and resilience to injury. Distinct roles for resident and recruited cells have been demonstrated in transplanted human heart but a universal fate-mapping tool is required to probe other tissues in health and diseased states. I have contributed to the phenotypic and transcriptomic description of human tissue macrophages, monocyte-derived cells and dendritic cells, now broadly adopted. In combination with fate-mapping this will provide a powerful overlay of ontogeny and function. Defining the origin of human microglia is of particular importance because they exemplify an exclusively primitive origin3. They also adopt a disease-associated phenotype expressing many risk loci for prevalent human neurodegenerative disease.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004985","title":"Transcriptomic analyses of female lung adenocarcinoma","description":"Comprehensive characterization of its transcriptomiclandscapes is crucial for cancer prevention and the development of precision therapy. Here, we report extensive transcriptomic profiles of 117  female lung adenocarcinoma (XWFA),  33 normal and 115 tumour mRNA-seq profiles.","abstract":"Comprehensive characterization of its transcriptomiclandscapes is crucial for cancer prevention and the development of precision therapy. Here, we report extensive transcriptomic profiles of 117  female lung adenocarcinoma (XWFA),  33 normal and 115 tumour mRNA-seq profiles.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001004986","title":"Genomic analyses of female lung adenocarcinoma","description":"Comprehensive characterization of its gemomic landscape is crucial for cancer prevention and the development of precision therapy. Here, we report extensive transcriptomic profiles of 117  female lung adenocarcinoma (XWFA), 112 paried tumor-normal mutation profiles.","abstract":"Comprehensive characterization of its gemomic landscape is crucial for cancer prevention and the development of precision therapy. Here, we report extensive transcriptomic profiles of 117  female lung adenocarcinoma (XWFA), 112 paried tumor-normal mutation profiles.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001004987","title":"High-grade serous ovarian cancer refined with single-cell RNA-sequencing","description":"We performed single-cell RNA-sequencing of 18,403 cells unbiasedly collected from 7 treatment-naive HGSOC tumours. For each phenotypic cluster of tumour or stromal cells, we identified specific transcriptomic markers. Next, we explored which phenotypic clusters correlate with overall survival based on expression of these transcriptomic markers in 1467 bulk RNA-seq tumours. By evaluating molecular subtype signatures in single cells, we assessed to what extent a phenotypic cluster of tumour or stromal cells contributes to each molecular subtype.","abstract":"We performed single-cell RNA-sequencing of 18,403 cells unbiasedly collected from 7 treatment-naive HGSOC tumours. For each phenotypic cluster of tumour or stromal cells, we identified specific transcriptomic markers. Next, we explored which phenotypic clusters correlate with overall survival based on expression of these transcriptomic markers in 1467 bulk RNA-seq tumours. By evaluating molecular subtype signatures in single cells, we assessed to what extent a phenotypic cluster of tumour or stromal cells contributes to each molecular subtype.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-24T14:52:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004988","title":"RNA-sequencing of gluten-reactive and non-reactive T-cells from blood samples of treated CeD patients during a gluten-challenge","description":"Gluten-specific CD4+ T cells are drivers of celiac disease (CeD). Here we aimed to characterize such cells in blood of treated CeD patients during gluten challenge with comparison to similar cells of untreated disease. \nTreated CeD patients underwent a 3-day gluten-challenge with blood sampling at baseline and day 6 (d6). Blood cells were stained with HLA-DQ:gluten tetramers (Tetramer). CD4+, gut-homing Tetramer+ and Tetramer- effector-memory T (TEM) cells at d6 were subjected to bulk RNA-seq (n=7).","abstract":"Gluten-specific CD4+ T cells are drivers of celiac disease (CeD). Here we aimed to characterize such cells in blood of treated CeD patients during gluten challenge with comparison to similar cells of untreated disease. \nTreated CeD patients underwent a 3-day gluten-challenge with blood sampling at baseline and day 6 (d6). Blood cells were stained with HLA-DQ:gluten tetramers (Tetramer). CD4+, gut-homing Tetramer+ and Tetramer- effector-memory T (TEM) cells at d6 were subjected to bulk RNA-seq (n=7).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-24T20:11:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004989","title":"Single-cell T-cell receptor sequencing of intraepithelial CD8+ αβ T-cells in celiac disease","description":"Single-cell paired TCR sequencing of intraepithelial CD8+ αβ T-cells in gluten-free diet treated and untreated celiac disease patients and in controls. (Paired end, amplicon sequencing).","abstract":"Single-cell paired TCR sequencing of intraepithelial CD8+ αβ T-cells in gluten-free diet treated and untreated celiac disease patients and in controls. (Paired end, amplicon sequencing).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-24T21:11:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004990","title":"Evolutionary dynamics of neuroblastoma","description":"Whole genome sequencing data of low risk neuroblastoma tumors and matching controls used to study the evolutionary dynamics of neuroblastoma.","abstract":"Whole genome sequencing data of low risk neuroblastoma tumors and matching controls used to study the evolutionary dynamics of neuroblastoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-25T09:42:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004991","title":"Hla_Diversity_In_African_Populations","description":"Very little is known about the genetic diversity of the Human Leukocyte Antigen (HLA) region in African populations, and the availability of sequences from African individuals from this region are limited in existing HLA databases. Given the importance of these regions in immune response to disease and the complex environments in which the different populations in Africa have evolved, it is vital to understand the diversity of this region among different populations within the African continent. Understanding this diversity is likely to provide important insights into selective adaptation to environment; differences in population disease susceptibility; and yield a useful resource for imputation, allowing greater resolution in GWAS of relevant traits. Undertaking an assessment of HLA genetic diversity in Africa may also be clinically relevant by providing better resolution of HLA types for transplant matching, vital for the operation of transplantation services within this region. Deconvolution of HLA haplotypes within these populations is difficult because of the limitations of existing methods, specifically their lack of resolution given the high variability of this region, and the absence of sequences from African populations in current references, making it difficult to delineate the haplotypes of these alleles in African populations.                                                                                                                                                                                     We recently carried out a pilot study of 125 individuals belonging to five distinct African ethno-linguistic groups from North, East, West and South Africa. Given the high genetic diversity in this region, and known difficulties with resolving ambiguous information in this region, we compared the current clinical gold standard for HLA typing (Sequence Based Typing, SBT, using capillary sequencing) with various emerging sequencing platforms, including single molecule real-time (SMRT) sequencing (PacBio) and HiSeq X sequencing. Our preliminary findings from 125 samples showed extensive diversity in HLA alleles among African samples, with a large proportion of alleles present in our data being completely absent among Europeans. Our preliminary results from 4 pilot samples that were sequenced with PacBio (GenDX primers) suggest material gains in identification of HLA alleles with six novel alleles (not previously reported in the IGMT database) identified among HLA class I, even in this limited number of samples. Furthermore, we observed marked ambiguity in the SBT calls (&gt;90% of HLA-C alleles), particularly for class I alleles suggesting that alternative methods may be required to explore this region in African populations. Correlation of HLA types between HiSeq X short read sequencing and SBT, the current clinical gold standard, were also poor, consistent with the known variability in this region, and poor reference sequences potentially resulting in poor mapping to these contigs across the genome. In the context of these preliminary findings, here we request funds to expand this study to PacBio sequencing of 5 populations of 25 individuals each, in order to characterise in detail the genetic diversity of this region. In addition to providing the first assessment of genetic diversity of this region in African populations, this will provide a global resource for researchers examining the HLA region in the context of disease susceptibility and response.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"We recently carried out a pilot study of 125 individuals belonging to five distinct African ethno-linguistic groups from North, East, West and South Africa. Given the high genetic diversity in this region, and known difficulties with resolving ambiguous information in this region, we compared the current clinical gold standard for HLA typing (Sequence Based Typing, SBT, using capillary sequencing) with various emerging sequencing platforms, including single molecule real-time (SMRT) sequencing (PacBio) and HiSeq X sequencing. In addition to providing the first assessment of genetic diversity of this region in African populations, this will provide a global resource for researchers examining the HLA region in the context of disease susceptibility and response.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004992","title":"Targeting the Epichaperome As an Effective Precision Medicine Approach in a Novel PML-SYK Fusion Acute Myeloid Leukemia","description":null,"abstract":"The epichaperome is a new cancer target composed of hyperconnected networks of chaperome members that facilitate cell survival. Cancers with an altered chaperone configuration may be susceptible to epichaperome inhibitors. We developed a flow cytometry-based assay for evaluation and monitoring of epichaperome abundance at the single cell level, with the goal of prospectively identifying patients likely to respond to epichaperome inhibitors, to measure target engagement, and dependency during treatment. As proof of principle, we describe a patient with an unclassified myeloproliferative neoplasm harboring a novel PML-SYK fusion, who progressed to acute myeloid leukemia despite chemotherapy and allogeneic stem cell transplant. The leukemia was identified as having high epichaperome abundance. We obtained compassionate access to an investigational epichaperome inhibitor, PU-H71. After 16 doses, the patient achieved durable complete remission. These encouraging results suggest that further investigation of epichaperome inhibitors in patients with abundant baseline epichaperome levels is warranted.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-26T14:49:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004993","title":"Whole exome sequencing from small cell lung cancer patients","description":"To identify genomic drivers present in limited-stage small cell lung cancer (LS-SCLC); To determine the overall tumor mutational burden in LS-SCLC; To determine genomic intratumor heterogeneity (ITH) in LS-SCLC.","abstract":"To identify genomic drivers present in limited-stage small cell lung cancer (LS-SCLC); To determine the overall tumor mutational burden in LS-SCLC; To determine genomic intratumor heterogeneity (ITH) in LS-SCLC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001004994","title":"Somatic mutations in lymphocytes in patients with immune-mediated aplastic anemia","description":null,"abstract":"In this study, we investigated somatic mutations of CD4+ and CD8+ T cells in patients with immune-mediated aplastic anemia (AA). To understand the role of mutations, we performed single-cell level analysis of 6 longitudinal samples of 2 AA patients carrying STAT3 or KRAS and other mutations in CD8+ T cells. The analysis was performed using V(D)J and 5' gene expression platform (10X Genomics). STAT3 mutated clone was clearly distinguishable from other CD8+ T cells and showed a cytotoxic phenotype, attenuated by successful immunosuppressive treatment. Our results suggest that somatic mutations in T cells can alter T cell phenotype warranting further investigation of their role in the pathogenesis of immune-mediated AA.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-27T08:07:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004995","title":"Peruvian Genome Project - Whole Genome Sequencing","description":"In this study, we sequence 150 genomes to high coverage from Native American and mestizo populations in Peru. The majority of our samples possess greater than 90% Native American ancestry, which makes this the most extensive Native American sequencing project to date.","abstract":"In this study, we sequence 150 genomes to high coverage from Native American and mestizo populations in Peru. The majority of our samples possess greater than 90% Native American ancestry, which makes this the most extensive Native American sequencing project to date.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-27T14:01:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004996","title":"Boson HCV infected liver bulk RNASeq study","description":"ACE2 is a receptor for the SARS-CoV-2 and differences in its expression may affect susceptibility to infection. In a genome-wide eQTL analysis using hepatitis C virus-infected liver tissue, we discovered that polymorphism in a type III interferon gene (IFNL4), which eliminates IFN-lambda-4 production, is associated with a two-fold increase in ACE2 RNA expression. Conversely, among genes negatively correlated with ACE2 expression, IFN-signalling pathways were highly enriched and ACE2 was downregulated after IFN-alpha treatment.","abstract":"ACE2 is a receptor for the SARS-CoV-2 and differences in its expression may affect susceptibility to infection. In a genome-wide eQTL analysis using hepatitis C virus-infected liver tissue, we discovered that polymorphism in a type III interferon gene (IFNL4), which eliminates IFN-lambda-4 production, is associated with a two-fold increase in ACE2 RNA expression. Conversely, among genes negatively correlated with ACE2 expression, IFN-signalling pathways were highly enriched and ACE2 was downregulated after IFN-alpha treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-27T15:27:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004997","title":"Clinical outcomes in ctDNA-positive urothelial carcinoma patients treated with adjuvant immunotherapy","description":"Minimally invasive approaches to detect residual disease after surgery are urgently needed to select patients at highest risk for metastatic relapse for additional therapies. Circulating tumour DNA (ctDNA) holds promise as a biomarker for molecular residual disease (MRD) and relapse,1-3 but its clinical value has yet to be demonstrated in a randomised clinical trial. We evaluated outcomes in post-surgical ctDNA-positive (+) patients in a randomised phase III trial of adjuvant atezolizumab versus observation. IMvigor010 enrolled 809 patients with muscle-invasive urothelial carcinoma and did not meet its primary endpoint of disease-free survival (DFS) in the intent-to-treat population. Within the study, an exploratory planned analysis of prospectively collected plasma was performed, which tested the utility of ctDNA to identify patients who may benefit from adjuvant atezolizumab treatment. ctDNA was measured at the start of therapy (cycle 1 day 1; C1D1) and at week 6 (cycle 3 day 1; C3D1), and 581 patients were evaluable for ctDNA. The prevalence of ctDNA positivity at C1D1 was 37% (n=214), and ctDNA positivity identified patients with poor prognosis (observation arm DFS HR= 6.19 (4.29, 8.91), p&amp;lt;0.0001). Here we show that ctDNA(+) patients had improved DFS and overall survival (OS) with atezolizumab versus observation (DFS HR= 0.56 (0.41-0.77); p=0.0003 and OS HR= 0.58 (0.4-0.86); p=0.0063). No difference in DFS or OS between arms was noted for ctDNA-negative patients. The rate of ctDNA clearance was higher with atezolizumab (18%) versus observation (4%) (p=0.0041). Transcriptomic analysis revealed that tumours from ctDNA(+) patients had higher expression of cell cycle and keratin genes. Within the ctDNA(+) patient population in the atezolizumab arm, non-relapsing patients were further enriched in prominent immune response signatures including PD-L1, IFNG, CXCL9, and high tumour mutational burden, whereas relapse was associated with angiogenesis and fibroblast-transforming growth factor-beta signatures (F-TBRS). TCGA molecular subset analysis revealed increased efficacy of atezolizumab in patients with basal-squamous tumours, consistent with underlying tumour-immune contexture. Together these findings suggest that adjuvant atezolizumab may be associated with improved outcomes compared with observation in this high-risk ctDNA(+) population. These findings, if validated in other settings, would shift approaches to post-operative cancer care.","abstract":"Minimally invasive approaches to detect residual disease after surgery are urgently needed to select patients at highest risk for metastatic relapse for additional therapies. Circulating tumour DNA (ctDNA) holds promise as a biomarker for molecular residual disease (MRD) and relapse,1-3 but its clinical value has yet to be demonstrated in a randomised clinical trial. We evaluated outcomes in post-surgical ctDNA-positive (+) patients in a randomised phase III trial of adjuvant atezolizumab versus observation. IMvigor010 enrolled 809 patients with muscle-invasive urothelial carcinoma and did not meet its primary endpoint of disease-free survival (DFS) in the intent-to-treat population. Within the study, an exploratory planned analysis of prospectively collected plasma was performed, which tested the utility of ctDNA to identify patients who may benefit from adjuvant atezolizumab treatment. ctDNA was measured at the start of therapy (cycle 1 day 1; C1D1) and at week 6 (cycle 3 day 1; C3D1), and 581 patients were evaluable for ctDNA. The prevalence of ctDNA positivity at C1D1 was 37% (n=214), and ctDNA positivity identified patients with poor prognosis (observation arm DFS HR= 6.19 (4.29, 8.91), p&amp;lt;0.0001). Here we show that ctDNA(+) patients had improved DFS and overall survival (OS) with atezolizumab versus observation (DFS HR= 0.56 (0.41-0.77); p=0.0003 and OS HR= 0.58 (0.4-0.86); p=0.0063). No difference in DFS or OS between arms was noted for ctDNA-negative patients. The rate of ctDNA clearance was higher with atezolizumab (18%) versus observation (4%) (p=0.0041). Transcriptomic analysis revealed that tumours from ctDNA(+) patients had higher expression of cell cycle and keratin genes. Within the ctDNA(+) patient population in the atezolizumab arm, non-relapsing patients were further enriched in prominent immune response signatures including PD-L1, IFNG, CXCL9, and high tumour mutational burden, whereas relapse was associated with angiogenesis and fibroblast-transforming growth factor-beta signatures (F-TBRS). TCGA molecular subset analysis revealed increased efficacy of atezolizumab in patients with basal-squamous tumours, consistent with underlying tumour-immune contexture. Together these findings suggest that adjuvant atezolizumab may be associated with improved outcomes compared with observation in this high-risk ctDNA(+) population. These findings, if validated in other settings, would shift approaches to post-operative cancer care.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-27T19:29:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004998","title":"The genomic landscape of childhood acute lymphoblastic leukaemia with intrachromosomal amplification of chromosome 21 (iAMP21-ALL)","description":"Intrachromosomal amplification of chromosome 21 (iAMP21) results from breakage-fusion-bridge cycles and chromothripsis defines a cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukemia (B-ALL) cases associated with a poor prognosis. To systematically characterize the mechanism of somatic alternations in iAMP21, we perform integrated genomic, cytogenetic and transcriptomic analysis of 128 cases.","abstract":"Intrachromosomal amplification of chromosome 21 (iAMP21) results from breakage-fusion-bridge cycles and chromothripsis defines a cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukemia (B-ALL) cases associated with a poor prognosis. To systematically characterize the mechanism of somatic alternations in iAMP21, we perform integrated genomic, cytogenetic and transcriptomic analysis of 128 cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-28T01:01:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001004999","title":"Whole genome sequencing of patients affected by acute intermittent porphyria","description":"Acute intermittent porphyria (AIP) is an hereditary rare metabolic disorder of incomplete penetrance, affecting the biosynthesis of heme. IAP is an autosomal dominant disorder, resulting in a substantial reduction of the activity of the hydroxymethylbilane synthase coding gene (HMBS). Most HMBS mutation carriers are asymptomatic and only between 10% and 20% of patients present acute attacks of the associated symptoms. Here, we sequenced whole genomes of 16 AIP patients.","abstract":"Acute intermittent porphyria (AIP) is an hereditary rare metabolic disorder of incomplete penetrance, affecting the biosynthesis of heme. IAP is an autosomal dominant disorder, resulting in a substantial reduction of the activity of the hydroxymethylbilane synthase coding gene (HMBS). Most HMBS mutation carriers are asymptomatic and only between 10% and 20% of patients present acute attacks of the associated symptoms. Here, we sequenced whole genomes of 16 AIP patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-28T16:36:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005000","title":"single cell sequencing of resting and Influenza-stimulated mononcluear phagocytes of African and Europeans with varying degree of ex-vivo susceptibility to Influenza","description":"There is considerable inter-individual immunological and clinical variability upon influenza A virus (IAV) infection in humans; yet, the factors underlying such heterogeneity remain elusive. Here, using an ex vivo cellular model that captures natural variation in the transcriptional responses of monocytes to IAV, we find significant differences in viral mRNA levels between individuals of African and European ancestry. Using single cell analyses, we show that the overall number of cells that will ultimately become infected, rather than the amount of viral transcript expression per cell, is the main driver of the surprisingly higher IAV mRNA levels detected in European cells. Finally, we identify 135 genes, including the interferon-stimulated genes IFITM3, MX1, and OAS3, for which basal mRNA expression levels associate with IAV mRNA levels post infection. Our findings reveal that basal differences in activation of IRF/STAT-induced antiviral mechanisms may contribute to individual and population disparities in susceptibility to IAV infection.","abstract":"There is considerable inter-individual immunological and clinical variability upon influenza A virus (IAV) infection in humans; yet, the factors underlying such heterogeneity remain elusive. Here, using an ex vivo cellular model that captures natural variation in the transcriptional responses of monocytes to IAV, we find significant differences in viral mRNA levels between individuals of African and European ancestry. Using single cell analyses, we show that the overall number of cells that will ultimately become infected, rather than the amount of viral transcript expression per cell, is the main driver of the surprisingly higher IAV mRNA levels detected in European cells. Finally, we identify 135 genes, including the interferon-stimulated genes IFITM3, MX1, and OAS3, for which basal mRNA expression levels associate with IAV mRNA levels post infection. Our findings reveal that basal differences in activation of IRF/STAT-induced antiviral mechanisms may contribute to individual and population disparities in susceptibility to IAV infection.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-28T16:48:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005001","title":"Relapse series of two Pediatric ALL patients","description":"In this proof of principle study, we performed whole genome sequencing of two cases with multiple relapses in order to investigate whether groups of mutations separated in time show distinct mutational signatures. In patient 1, who experienced two relapses, the analysis unraveled a continuous interplay of aberrant AID/APOBEC-associated activities. Patient 2 had three relapses. We identified episodic mutational processes at diagnosis and first relapse leading to mutations resembling UV light-driven DNA damage, and thiopurine-associated damage at first relapse.","abstract":"In this proof of principle study, we performed whole genome sequencing of two cases with multiple relapses in order to investigate whether groups of mutations separated in time show distinct mutational signatures. In patient 1, who experienced two relapses, the analysis unraveled a continuous interplay of aberrant AID/APOBEC-associated activities. Patient 2 had three relapses. We identified episodic mutational processes at diagnosis and first relapse leading to mutations resembling UV light-driven DNA damage, and thiopurine-associated damage at first relapse.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-29T09:08:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005002","title":"Conformation_of_results_by_PCR","description":"This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Conformation of results by PCR","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005003","title":"MPN_bisulphite","description":"Evolution of the cancer epigenome in myeloproliferative neoplasms.","abstract":"Cancer clones emerge and evolve through somatic mutation acquisition and Darwinian selection, but the dynamics of clonal evolution remain poorly understood and predicting disease progression remains a real challenge. Genes that regulate the epigenome are clearly important targets of mutations in cancer, but the mechanisms by which they drive tumour evolution remain unknown.\nThe myeloproliferative neoplasms (MPN) are haematopoietic disorders that represent an excellent model to study genomic and epigenomic evolution in human cancers: (i) They are genetically well-defined with disease driving mutations in JAK2, CALR (which I described in 2013) or MPL, present alongside mutations in epigenetic regulators, such as, DNMT3A. (ii) Disease can be either stable, or progress to leukaemia or myelofibrosis, providing the opportunity to study the basis for these evolutionary differences, and (iii) Primary cells can be serially sampled at the clonal level enabling inter- and intra-clonal studies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005004","title":"Fibromyalgia versus small fiber neuropathy: Diverse keratinocyte transcriptome signature","description":"We provide a diverse keratinocyte transcriptome signature between SFN and FMS patients, which may hint towards distinct pathomechanisms of small fiber sensitization and lay the basis for advanced diagnostics in both entities","abstract":"We provide a diverse keratinocyte transcriptome signature between SFN and FMS patients, which may hint towards distinct pathomechanisms of small fiber sensitization and lay the basis for advanced diagnostics in both entities","study_type":"Other","pubmed_ids":[33675632],"external_links":null,"is_released":true,"released_date":"2021-01-29T12:13:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005005","title":"Genetic heterogeneity and dynamics of transcriptional subtypes in matched primary and recurrent head and neck squamous cell carcinomas","description":"To get a better understanding of different HNSCC subtypes, whole-exome (matched tumor-normal paits) and whole transcriptome sequencing to to elucidate underlying molecular processes. Here, we present the matched whole-exome sequencing data from 28 patients (normal tissue, tumor tissue, relapse).","abstract":"To get a better understanding of different HNSCC subtypes, whole-exome (matched tumor-normal paits) and whole transcriptome sequencing to to elucidate underlying molecular processes. Here, we present the matched whole-exome sequencing data from 28 patients (normal tissue, tumor tissue, relapse).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-30T08:12:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005006","title":"Longitudinal single-cell RNA-seq data of metastatic ovarian cancer","description":null,"abstract":"To characterize transcriptional patterns of chemotherapy resistance in HGSOC, we prospectively collected tissue samples before and after chemotherapy from 11 patients and analyzed their transcriptomic profiles at single-cell resolution.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-30T15:32:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005007","title":"IBD_Whole_Exome_Sequencing_","description":"Whole exome sequencing of patients with Inflammatory Bowel Disease","abstract":"In this study we will undertake whole-exome sequencing of UK IBD cases, this data will be combined with that from IBD cases we have already whole-genome sequenced in 2018, 2019 and 2020.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005008","title":"Mutations in the RAS/MAPK pathway drive replication repair deficient hypermutated tumors and confer sensitivity to MEK inhibition","description":"The RAS/MAPK pathway is an emerging targeted pathway across a spectrum of both adult and pediatric cancers. Typically, this is associated with a single, well-characterized point mutation in an oncogene. Hypermutant tumors which harbor many somatic mutations may obscure the interpretation of such targetable genomic events. We find that replication repair deficient (RRD) cancers which are universally hypermutant and affect children born with RRD cancer predisposition, are enriched for RAS/MAPK mutations (p=10-8). These mutations are not random, exist in subclones, and increase in allelic frequency over time. The RAS/MAPK pathway is activated both transcriptionally and at the protein level in patient derived RRD tumors and these tumors responded to MEK inhibition in vitro and in vivo. Treatment of patients with RAS/MAPK hypermutant gliomas reveal durable responses to MEK inhibition. Our observations suggest that hypermutant tumors may be addicted to oncogenic pathways resulting in favorable response to targeted therapies.","abstract":"The RAS/MAPK pathway is an emerging targeted pathway across a spectrum of both adult and pediatric cancers. Typically, this is associated with a single, well-characterized point mutation in an oncogene. Hypermutant tumors which harbor many somatic mutations may obscure the interpretation of such targetable genomic events. We find that replication repair deficient (RRD) cancers which are universally hypermutant and affect children born with RRD cancer predisposition, are enriched for RAS/MAPK mutations (p=10-8). These mutations are not random, exist in subclones, and increase in allelic frequency over time. The RAS/MAPK pathway is activated both transcriptionally and at the protein level in patient derived RRD tumors and these tumors responded to MEK inhibition in vitro and in vivo. Treatment of patients with RAS/MAPK hypermutant gliomas reveal durable responses to MEK inhibition. Our observations suggest that hypermutant tumors may be addicted to oncogenic pathways resulting in favorable response to targeted therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-30T17:28:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005009","title":"DO NOT USE - Whole genome sequencing of SI-NETs from six patients","description":"Small intestine neuroendocrine tumor (SI-NET), the most common cancer of the small bowel, often displays a curious multifocal phenotype with several intestinal tumors centered around a regional lymph node metastasis, yet the typical path of evolution of these lesions remains unclear. Here, we determined the complete genome sequences of 24 tumor and 3 adjacent normal tissue samples with their paired normal blood samples (totally 33 whole genomes) from 6 patients with multifocal SI-NETs, allowing elucidation of phylogenetic relationships between multiple intestinal tumors and metastases in individual patients.","abstract":"Small intestine neuroendocrine tumor (SI-NET), the most common cancer of the small bowel, often displays a curious multifocal phenotype with several intestinal tumors centered around a regional lymph node metastasis, yet the typical path of evolution of these lesions remains unclear. Here, we determined the complete genome sequences of 24 tumor and 3 adjacent normal tissue samples with their paired normal blood samples (totally 33 whole genomes) from 6 patients with multifocal SI-NETs, allowing elucidation of phylogenetic relationships between multiple intestinal tumors and metastases in individual patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-01-31T01:57:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005010","title":"Longitudinal single-cell RNA-seq data of metastatic ovarian cancer","description":null,"abstract":"To characterize transcriptional patterns of chemotherapy resistance in HGSOC, we prospectively collected tissue samples before and after chemotherapy from 11 patients and analyzed their transcriptomic profiles at single-cell resolution.","study_type":"Other","pubmed_ids":[35196078],"external_links":null,"is_released":true,"released_date":"2021-01-31T10:44:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005011","title":"Whole exome sequencing patient with MBD4 variant","description":"We performed a Whole Exome Sequencing on 9 Uveal Melanoma patient carrying a MBD4 variant and having both germline and tumor samples available.","abstract":"We performed a Whole Exome Sequencing on 9 Uveal Melanoma patient carrying a MBD4 variant and having both germline and tumor samples available.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005012","title":"MBD4 targeted sequencing","description":"We sequenced a gene of interest, MBD4, in both germline (n=1099) and tumor (n=192) sample from Uveal Melanoma patients.","abstract":"We sequenced a gene of interest, MBD4, in both germline (n=1099) and tumor (n=192) sample from Uveal Melanoma patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-01T16:57:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005013","title":"Intratumoral plasma cells predict outcomes to PD-L1 blockade in non-small cell lung cancer","description":"Inhibitors of the programmed cell death-1 (PD-1/PD-L1) signaling axis are approved to treat non-small cell lung cancer (NSCLC) patients, based on their significant overall survival (OS) benefit.  Using transcriptomic analysis of 891 NSCLC tumors from patients treated with either the PD-L1 inhibitor atezolizumab or chemotherapy from two large randomized clinical trials, we found a significant B cell association with extended OS with PD-L1 blockade, independent of CD8+ T cell signals. We then derived gene signatures corresponding to the dominant B cell subsets present in NSCLC from single-cell RNA-seq data. Importantly, we found increased plasma cell signatures to be predictive of OS in patients treated with atezolizumab, but not chemotherapy. B cells were also associated with the presence of tertiary lymphoid structures and organized lymphoid aggregates. Our results suggest an important contribution of B and plasma cells to PD-L1 blockade efficacy in NSCLC.","abstract":"Inhibitors of the programmed cell death-1 (PD-1/PD-L1) signaling axis are approved to treat non-small cell lung cancer (NSCLC) patients, based on their significant overall survival (OS) benefit.  Using transcriptomic analysis of 891 NSCLC tumors from patients treated with either the PD-L1 inhibitor atezolizumab or chemotherapy from two large randomized clinical trials, we found a significant B cell association with extended OS with PD-L1 blockade, independent of CD8+ T cell signals. We then derived gene signatures corresponding to the dominant B cell subsets present in NSCLC from single-cell RNA-seq data. Importantly, we found increased plasma cell signatures to be predictive of OS in patients treated with atezolizumab, but not chemotherapy. B cells were also associated with the presence of tertiary lymphoid structures and organized lymphoid aggregates. Our results suggest an important contribution of B and plasma cells to PD-L1 blockade efficacy in NSCLC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-01T17:56:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005014","title":"Primary prostate Hi-C","description":"Prostate cancer is a heterogeneous disease whose progression is linked to genome instability. Despite large-scale tumour sequencing efforts, the impact of mutations on the genetic architecture in cancer remains ill-defined due to limited integration of genomics data across dimensions. We addressed this limitation by assessing the impact of structural variants on the chromatin states and the three-dimensional organization across benign and malignant primary prostate genomes. We find high concordance in the three-dimensional genome organization between malignant and benign prostate tissues, arguing for constraints to the three-dimensional genome of prostate tumours. Moreover, we identify structural variants as effectors of changes to focal chromatin interactions, guiding cis-regulatory element hijacking that imposes opposing expression changes on genes found at antipodes of a rearrangement. This leads to the repression of tumour suppressor gene expression and up-regulation of oncogenes, such as at the TMPRSS2-ERG and PMEPA1-ZNF156 loci. Collectively, our results argue that cis-regulatory element hijacking by structural variants overshadows large-scale topological changes to alter gene regulation and promote oncogenesis.","abstract":"Prostate cancer is a heterogeneous disease whose progression is linked to genome instability. Despite large-scale tumour sequencing efforts, the impact of mutations on the genetic architecture in cancer remains ill-defined due to limited integration of genomics data across dimensions. We addressed this limitation by assessing the impact of structural variants on the chromatin states and the three-dimensional organization across benign and malignant primary prostate genomes. We find high concordance in the three-dimensional genome organization between malignant and benign prostate tissues, arguing for constraints to the three-dimensional genome of prostate tumours. Moreover, we identify structural variants as effectors of changes to focal chromatin interactions, guiding cis-regulatory element hijacking that imposes opposing expression changes on genes found at antipodes of a rearrangement. This leads to the repression of tumour suppressor gene expression and up-regulation of oncogenes, such as at the TMPRSS2-ERG and PMEPA1-ZNF156 loci. Collectively, our results argue that cis-regulatory element hijacking by structural variants overshadows large-scale topological changes to alter gene regulation and promote oncogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-01T23:08:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005015","title":"RNA sequencing of PTCL-NOS","description":null,"abstract":"To further improve our understanding of the genetic landscape and biology of PTCL-NOS, we performed RNA-sequencing of 15 cases. We describe a recurrent FYN-TRAF3IP2 fusion transcript in PTCL-NOS and PTCL-TFH and a KHDRBS1-LCK fusion transcript in PTCL-NOS.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-02T01:39:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005016","title":"Genome-wide characterization of Kuwaiti Arab populations","description":null,"abstract":"The aim of the study is to delineate the genetic substructures of the Kuwaiti population and to characterize them in the context  of the populations from the Arabian Peninsula. It is further aimed to compare the structures with those of global populations.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005017","title":"HCA_Immune_Foetal_WSSS_Spatial","description":"Spatial cell atlas of the developing human immune system","abstract":"The Human Developmental Cell Atlas aims to generate a reference map of cells from a fertilised oocyte to birth. This reference data will help accelerate progress in science and medicine, particularly relating to human development and disease. This project will involve single cell epigenome, transcriptome and nuclei profiling as well as spatial genomics analysis of the developing human immune system. We have generated single cell RNA sequencing data of fetal tissues between 7 and 17PCW including spleen, liver, thymus, skin and yolk sac. Collaborative access and integration of single cell data collected from fetal gut, lung and kidney further extends the utility of this combinatorial dataset. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005018","title":"Exome sequencing reveals pathogenic variants in known and novel candidate genes for severe sperm motility disorders","description":"STUDY QUESTION: What are the causative genetic variants in patients with male infertility due to severe sperm motility disorders?\n\nSUMMARY ANSWER: We identified high confidence disease-causing variants in multiple genes previously associated with severe sperm motility disorders in 9 out of 21 patients (43%). We also identified variants in novel candidate genes in 8 additional patients (38%).\n\nWHAT IS KNOWN ALREADY: Severe sperm motility disorders are a form of male infertility characterised by vital, but immotile sperm often in combination with a spectrum of structural abnormalities of the sperm flagellum. Examples of this spectrum of disorders include dysplasia of the fibrous sheath / multiple morphological abnormalities of the sperm flagella (DFS-MMAF) and severe forms of asthenozoospermia associated to non-specific structural defects. These disorders frequently recur in families and may include chronic respiratory disease. As such, genetic causes are suspected and many genes have recently been reported. Currently, depending on the clinical sub-categorisation, up to 50% of causality in patients with severe sperm motility disorders can be explained by pathogenic variants in at least 21 known genes.\n\nSTUDY DESIGN, SIZE, DURATION: We performed exome sequencing in patients with severe sperm motility disorders from two different clinics, aiming to identify the underlying genetic defects and establishing a diagnostic yield in both.\n\nPARTICIPANTS/MATERIALS, SETTING, METHOD: Two groups of infertile men, one from Argentina (n= 9) and one from Australia (n=12), with clinically defined sperm motility disorders were included. All patients in the Argentine cohort were diagnosed with DFS-MMAF, based on transmission electron microscopy. Exome sequencing was performed in all 21 patients and variants with an allele frequency of &lt;1% in the gnomAD population were prioritised and interpreted.\n\nMAIN RESULTS AND ROLE OF CHANCE: In 9/21 patients (43%), we identified pathogenic variants in known sperm motility disorder genes: CFAP43 (3 patients); CFAP44 (2 patients), QRICH2 (2 patients), DNAH1 (1 patient) and DNAH6 (1 patient). The diagnostic rate did not differ markedly between the Argentinian and the Australian cohort (44% and 42%, respectively). Furthermore, we identified patients with variants in the novel candidate sperm motility genes CFAP58, DNAH12, DRC1, MDC1, PACRG, SSPL2C and TPTE2. One patient presented with two possibly damaging variants in four candidate genes and it remains unclear which variants were responsible for the severe sperm motility defect in this patient.\n\nLIMITATIONS, REASONS FOR CAUTION: In this study, we described patients with potential bi-allelic variants in known and novel candidate genes for severe sperm motility disorders. Due to unavailability of parental DNA, we have not assessed de novo or maternally inherited dominant variants and could not phase the mutations to establish in all cases that the mutations occur on both alleles.\n\nWIDER IMPLICATIONS OF THE FINDINGS: Our results confirm an important role for five known genes for sperm motility and we demonstrate that exome sequencing is an effective method to diagnose patients with severe sperm motility defects (9/21 diagnosed; 43%). Furthermore, our analysis revealed seven novel candidate genes for severe sperm motility disorders. Genome-wide sequencing of additional patient cohorts and re-analysis of exome data of currently unsolved cases may reveal additional variants in these novel candidate genes.","abstract":"STUDY QUESTION: What are the causative genetic variants in patients with male infertility due to severe sperm motility disorders?\n\nSUMMARY ANSWER: We identified high confidence disease-causing variants in multiple genes previously associated with severe sperm motility disorders in 9 out of 21 patients (43%). We also identified variants in novel candidate genes in 8 additional patients (38%).\n\nWHAT IS KNOWN ALREADY: Severe sperm motility disorders are a form of male infertility characterised by vital, but immotile sperm often in combination with a spectrum of structural abnormalities of the sperm flagellum. Examples of this spectrum of disorders include dysplasia of the fibrous sheath / multiple morphological abnormalities of the sperm flagella (DFS-MMAF) and severe forms of asthenozoospermia associated to non-specific structural defects. These disorders frequently recur in families and may include chronic respiratory disease. As such, genetic causes are suspected and many genes have recently been reported. Currently, depending on the clinical sub-categorisation, up to 50% of causality in patients with severe sperm motility disorders can be explained by pathogenic variants in at least 21 known genes.\n\nSTUDY DESIGN, SIZE, DURATION: We performed exome sequencing in patients with severe sperm motility disorders from two different clinics, aiming to identify the underlying genetic defects and establishing a diagnostic yield in both.\n\nPARTICIPANTS/MATERIALS, SETTING, METHOD: Two groups of infertile men, one from Argentina (n= 9) and one from Australia (n=12), with clinically defined sperm motility disorders were included. All patients in the Argentine cohort were diagnosed with DFS-MMAF, based on transmission electron microscopy. Exome sequencing was performed in all 21 patients and variants with an allele frequency of &lt;1% in the gnomAD population were prioritised and interpreted.\n\nMAIN RESULTS AND ROLE OF CHANCE: In 9/21 patients (43%), we identified pathogenic variants in known sperm motility disorder genes: CFAP43 (3 patients); CFAP44 (2 patients), QRICH2 (2 patients), DNAH1 (1 patient) and DNAH6 (1 patient). The diagnostic rate did not differ markedly between the Argentinian and the Australian cohort (44% and 42%, respectively). Furthermore, we identified patients with variants in the novel candidate sperm motility genes CFAP58, DNAH12, DRC1, MDC1, PACRG, SSPL2C and TPTE2. One patient presented with two possibly damaging variants in four candidate genes and it remains unclear which variants were responsible for the severe sperm motility defect in this patient.\n\nLIMITATIONS, REASONS FOR CAUTION: In this study, we described patients with potential bi-allelic variants in known and novel candidate genes for severe sperm motility disorders. Due to unavailability of parental DNA, we have not assessed de novo or maternally inherited dominant variants and could not phase the mutations to establish in all cases that the mutations occur on both alleles.\n\nWIDER IMPLICATIONS OF THE FINDINGS: Our results confirm an important role for five known genes for sperm motility and we demonstrate that exome sequencing is an effective method to diagnose patients with severe sperm motility defects (9/21 diagnosed; 43%). Furthermore, our analysis revealed seven novel candidate genes for severe sperm motility disorders. Genome-wide sequencing of additional patient cohorts and re-analysis of exome data of currently unsolved cases may reveal additional variants in these novel candidate genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-02T11:49:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005019","title":"Longitudinal Single-Cell Profiling Reveals Molecular Heterogeneity and Tumor-Immune Evolution in Refractory Mantle Cell Lymphoma","description":"The mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that the molecular targeting of BIRC5/survivin, locates at 17q and upregulates in resistant MCL tumor cells, results in marked tumor inhibition in preclinical models. In addition, we discovere notable differences in the tumor microenvironment including progressive dampening of CD8+ T cells and aberrant cell-to-cell communication networks in refractory MCLs. This study reveales diverse and dynamic tumor and immune programs underlying therapy resistance in MCL.","abstract":"The mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that the molecular targeting of BIRC5/survivin, locates at 17q and upregulates in resistant MCL tumor cells, results in marked tumor inhibition in preclinical models. In addition, we discovere notable differences in the tumor microenvironment including progressive dampening of CD8+ T cells and aberrant cell-to-cell communication networks in refractory MCLs. This study reveales diverse and dynamic tumor and immune programs underlying therapy resistance in MCL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-02T12:54:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005020","title":"Gut metagenome/FINRISK 2002 (Salosensaari et al. Nature Comms 2021)","description":"The main goal of the project is the study the associations between the gut metagenome and human health. The dataset contains data for n=7211 FINRISK 2002 participants who underwent fecal sampling. Demultiplexed shallow shotgun metagenomic sequences were quality filtered and adapter trimmed using Atropos (Didion et al., 2017), and human filtered using Bowtie2 (Langmead and Salzberg, 2012).","abstract":"The main goal of the project is the study the associations between the gut metagenome and human health. The dataset contains data for n=7211 FINRISK 2002 participants who underwent fecal sampling. Demultiplexed shallow shotgun metagenomic sequences were quality filtered and adapter trimmed using Atropos (Didion et al., 2017), and human filtered using Bowtie2 (Langmead and Salzberg, 2012).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-02T17:22:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005021","title":"Single cell RNAseq of lung adenocarcinoma","description":"Little is known of the geospatial architecture of individual cell populations in lung adenocarcinoma (LUAD) evolution. Here, we perform single-cell RNA sequencing as well as single-cell BCR sequencing of cells from 16 LUADs and 47 multi-region normal lung tissues of defined spatial proximities from the tumors. Our multi-region single-cell sequencing analyses unravel cell populations, states, and phenotypes in the spatial and ecological evolution LUAD from the lung that comprise high-potential targets for early interception.","abstract":"Little is known of the geospatial architecture of individual cell populations in lung adenocarcinoma (LUAD) evolution. Here, we perform single-cell RNA sequencing as well as single-cell BCR sequencing of cells from 16 LUADs and 47 multi-region normal lung tissues of defined spatial proximities from the tumors. Our multi-region single-cell sequencing analyses unravel cell populations, states, and phenotypes in the spatial and ecological evolution LUAD from the lung that comprise high-potential targets for early interception.","study_type":"Other","pubmed_ids":[36098652],"external_links":null,"is_released":true,"released_date":"2021-02-03T14:56:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005022","title":"Deep genetic affinity between coastal Pacific and Amazonian natives evidenced by Australasian ancestry","description":"Analysis of the genetic affinity between coastal Pacific and Amazonian natives (i.e. \"Y population\" ancestry). Here we analyzed a dataset of newly generated data from four Brazilian indigenous communities genotyped in the Axiom Human Origins array combined with publicly available data from other Native American populations.","abstract":"Analysis of the genetic affinity between coastal Pacific and Amazonian natives (i.e. \"Y population\" ancestry). Here we analyzed a dataset of newly generated data from four Brazilian indigenous communities genotyped in the Axiom Human Origins array combined with publicly available data from other Native American populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-03T18:59:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005023","title":"Kalirin-RAC controls nucleokinetic migration in ADRN-type neuroblastoma","description":"The migrational propensity of neuroblastoma is affected by cell identity, but the mechanisms behind the divergence remain unknown. Using RNAi and time-lapse imaging, we show that ADRN-type NB cells exhibit RAC1- and kalirin-dependent nucleokinetic (NUC) migration that relies on several integral components of neuronal migration. Inhibition of NUC migration by RAC1 and kalirin-GEF1 inhibitors occurs without hampering cell proliferation and ADRN identity. Using three clinically-relevant expression dichotomies, we reveal that most of up-regulated mRNAs in RAC1- and kalirin-GEF1-suppressed ADRN-type NB cells are associated with low-risk characteristics. The computational analysis shows that, in a context of overall gene set poverty, the upregulomes in RAC1- and kalirin-GEF1-suppressed ADRN-type cells are a batch of AU-rich elements (ARE)-containing mRNAs, which suggests a link between NUC migration and mRNA stability. GSEA-based search for vulnerabilities reveals prospective weak points in RAC1- and kalirin-GEF1-suppressed ADRN-type NB cells, including activities of H3K27- and DNA methyltransferases. Altogether, these data support the introduction of NUC inhibitors into cancer treatment research.","abstract":"The migrational propensity of neuroblastoma is affected by cell identity, but the mechanisms behind the divergence remain unknown. Using RNAi and time-lapse imaging, we show that ADRN-type NB cells exhibit RAC1- and kalirin-dependent nucleokinetic (NUC) migration that relies on several integral components of neuronal migration. Inhibition of NUC migration by RAC1 and kalirin-GEF1 inhibitors occurs without hampering cell proliferation and ADRN identity. Using three clinically-relevant expression dichotomies, we reveal that most of up-regulated mRNAs in RAC1- and kalirin-GEF1-suppressed ADRN-type NB cells are associated with low-risk characteristics. The computational analysis shows that, in a context of overall gene set poverty, the upregulomes in RAC1- and kalirin-GEF1-suppressed ADRN-type cells are a batch of AU-rich elements (ARE)-containing mRNAs, which suggests a link between NUC migration and mRNA stability. GSEA-based search for vulnerabilities reveals prospective weak points in RAC1- and kalirin-GEF1-suppressed ADRN-type NB cells, including activities of H3K27- and DNA methyltransferases. Altogether, these data support the introduction of NUC inhibitors into cancer treatment research.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-03T20:20:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005024","title":"Proteotranscriptomic classification and characterization of pancreatic neuroendocrine neoplasms","description":"Pancreatic neuroendocrine neoplasms (PNENs) are biologically and clinically heterogeneous neoplasms. We used a multi-omics approach to uncover the molecular factors underlying this heterogeneity and derive a potential disease classification. Transcriptomic analysis of 84 primary PNEN specimens, drawn from two cohorts (n = 36 and 48), identified four subgroups with distinct molecular profiles. Whole-exome sequencing revealed subgroup-enriched mutational differences.","abstract":"Pancreatic neuroendocrine neoplasms (PNENs) are biologically and clinically heterogeneous neoplasms. We used a multi-omics approach to uncover the molecular factors underlying this heterogeneity and derive a potential disease classification. Transcriptomic analysis of 84 primary PNEN specimens, drawn from two cohorts (n = 36 and 48), identified four subgroups with distinct molecular profiles. Whole-exome sequencing revealed subgroup-enriched mutational differences.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-03T20:29:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005025","title":"Transcriptomic and epigentic analysis of human peripheral blood NK cell subsets revealing role of Bcl11b in differentiation","description":"Transcriptomic analysis of seven human peripheral blood NK cell subsets and three T cell subsets purified from healthy cytomeglovirus seropositive donors.\nEpigenetic analysis including identification of open chromatin and active enhancer elements confirms key regulatory factors defining an NK cell differentiation axis.\nChromatin-immunoprecipitation sequencing reveals contribution of key transcription factors associated with NK cell differentiation including Bcl11b.","abstract":"Transcriptomic analysis of seven human peripheral blood NK cell subsets and three T cell subsets purified from healthy cytomeglovirus seropositive donors.\nEpigenetic analysis including identification of open chromatin and active enhancer elements confirms key regulatory factors defining an NK cell differentiation axis.\nChromatin-immunoprecipitation sequencing reveals contribution of key transcription factors associated with NK cell differentiation including Bcl11b.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-04T00:48:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005026","title":"Summary statistics of meta-analysis using two genome-wide association study of inflammatory bowel disease in Koreans.","description":"Inflammatory bowel disease (IBD), a chronic inflammatory disorder of the gastrointestinal tract, is thought to develop due to dysregulated mucosal immune responses to gut flora in genetically susceptible individuals. Crohn’s disease (CD) and ulcerative colitis (UC) are the two major subtypes of IBD. To identify additional susceptibility loci for IBD in Asians, we performed meta-analyses using two genome-wide association studies.","abstract":"Inflammatory bowel disease (IBD), a chronic inflammatory disorder of the gastrointestinal tract, is thought to develop due to dysregulated mucosal immune responses to gut flora in genetically susceptible individuals. Crohn’s disease (CD) and ulcerative colitis (UC) are the two major subtypes of IBD. To identify additional susceptibility loci for IBD in Asians, we performed meta-analyses using two genome-wide association studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-04T05:34:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005027","title":"The Dutch Microbiome Project: Defining the (un)healthy gut microbiome","description":"The Dutch Microbiome Project (DMP) data includes raw data generated by shotgun metagenomic sequencing of faecal samples of 8,208 Dutch individuals, processed microbiome data analysed using Biobakery2 tools (including taxonomy, pathway, virulence factors and antibiotic resistance gene profiles), and basic phenotypes (age and sex, BMI). Data is made available in two randomly assigned batches to facilitate the data access and maintenance. \n\n\nAccess to this dataset requires a minimal access procedure (data access form at https://forms.gle/eHeBdXJMXbVvCJRc8 or email request to the data access committee (DAC) of this study, listed at DAC EGAC00001001996, https://ega-archive.org/dacs/EGAC00001001996). This access procedure is to ensure that the data is being requested for research/scientific purposes only and thus complies with the informed consent signed by Lifelines participants, which specifies that the collected data will not be used for commercial purposes. Submitted data access forms will be evaluated by the DAC and Lifelines, and a response to requests will be given within two weeks. For requests from verified academic parties, access will be given without further delay. For requests from commercial parties, Lifelines will perform a pre-DPIA (Data Privacy Impact Assessment) to assess the risks of the proposed processing of personal data (e.g. purpose, storage, access, archiving, etc.) with respect to the GDPR (EU privacy laws) subject rights. Based on the outcome of the pre-DPIA, Lifelines will decide whether sharing data with the commercial entity is allowed and/or whether additional measures have to be taken.","abstract":"The Dutch Microbiome Project (DMP) data includes raw data generated by shotgun metagenomic sequencing of faecal samples of 8,208 Dutch individuals, processed microbiome data analysed using Biobakery2 tools (including taxonomy, pathway, virulence factors and antibiotic resistance gene profiles), and basic phenotypes (age and sex, BMI). Data is made available in two randomly assigned batches to facilitate the data access and maintenance. \n\n\nAccess to this dataset requires a minimal access procedure (data access form at https://forms.gle/eHeBdXJMXbVvCJRc8 or email request to the data access committee (DAC) of this study, listed at DAC EGAC00001001996, https://ega-archive.org/dacs/EGAC00001001996). This access procedure is to ensure that the data is being requested for research/scientific purposes only and thus complies with the informed consent signed by Lifelines participants, which specifies that the collected data will not be used for commercial purposes. Submitted data access forms will be evaluated by the DAC and Lifelines, and a response to requests will be given within two weeks. For requests from verified academic parties, access will be given without further delay. For requests from commercial parties, Lifelines will perform a pre-DPIA (Data Privacy Impact Assessment) to assess the risks of the proposed processing of personal data (e.g. purpose, storage, access, archiving, etc.) with respect to the GDPR (EU privacy laws) subject rights. Based on the outcome of the pre-DPIA, Lifelines will decide whether sharing data with the commercial entity is allowed and/or whether additional measures have to be taken.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-05T11:37:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005028","title":"Merkel cell polyomavirus-negative -Merkel cell carcinoma originating from in situ squamous cell carcinoma: a keratinocytic tumor with neuroendocrine differentiation","description":null,"abstract":"Whole exome sequencing of four combined tumors consisting of SCC in situ and MCPyV-negative MCC demonstrated in all cases hundreds of mutations shared between SCC and MCC indicating a common ancestry and thereby a keratinocytic origin of these MCCs","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005029","title":"Monitoring of leukemia clones in B-cell acute lymphoblastic leukemia at diagnosis and during treatment by single-cell DNA amplicon sequencing","description":"Acute lymphoblastic leukemia (ALL) is characterized by the presence of chromosomal changes, including numerical changes, translocations and deletions, which are often associated with additional single nucleotide mutations. In this study we used single-cell targeted DNA sequencing to determine the clonal heterogeneity of B-cell ALL at diagnosis and during chemotherapy treatment. With a customly designed DNA amplicon library targeting the most common mutations (in 110 genes) present in ALL, we analyzed bone marrow samples and/or blood samples from 12 B-ALL cases at diagnosis. For 4 cases where we detected multiple mutational clones at diagnosis, we also studied blood samples during the first weeks of chemotherapy treatment. This study shows that B-ALL cases with either a ETV6-RUNX1 or a BCR-ABL1 fusion have a low mutational burden, while cases with PAX5 alterations or hyperdyploidy have multiple clones at diagnosis, often with mutations in the JAK-STAT signaling pathway and the RAS signaling pathway.  \nAs expected, it can be observed that these clones disappear during treatment of the leukemia with almost no mutated cells left after two weeks of treatment.","abstract":"Acute lymphoblastic leukemia (ALL) is characterized by the presence of chromosomal changes, including numerical changes, translocations and deletions, which are often associated with additional single nucleotide mutations. In this study we used single-cell targeted DNA sequencing to determine the clonal heterogeneity of B-cell ALL at diagnosis and during chemotherapy treatment. With a customly designed DNA amplicon library targeting the most common mutations (in 110 genes) present in ALL, we analyzed bone marrow samples and/or blood samples from 12 B-ALL cases at diagnosis. For 4 cases where we detected multiple mutational clones at diagnosis, we also studied blood samples during the first weeks of chemotherapy treatment. This study shows that B-ALL cases with either a ETV6-RUNX1 or a BCR-ABL1 fusion have a low mutational burden, while cases with PAX5 alterations or hyperdyploidy have multiple clones at diagnosis, often with mutations in the JAK-STAT signaling pathway and the RAS signaling pathway.  \nAs expected, it can be observed that these clones disappear during treatment of the leukemia with almost no mutated cells left after two weeks of treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-08T08:04:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005030","title":"MicroRNA profiling by next-generation sequencing for colorectal cancer screening","description":"The study was conducted as the marker discovery phase to identify potential microRNA (miRNA) candidates for colorectal cancer (CRC) screening. Genome-wide profiling with next-generation sequencing (NGS) was performed using plasma samples from 20 newly diagnosed CRC cases and 20 controls free of colorectal neoplasms matched by age and sex.","abstract":"The study was conducted as the marker discovery phase to identify potential microRNA (miRNA) candidates for colorectal cancer (CRC) screening. Genome-wide profiling with next-generation sequencing (NGS) was performed using plasma samples from 20 newly diagnosed CRC cases and 20 controls free of colorectal neoplasms matched by age and sex.","study_type":"Other","pubmed_ids":[34376648],"external_links":null,"is_released":true,"released_date":"2021-02-08T11:15:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005031","title":"Spinal_Cord_Regeneration_Study","description":"Bayraktar Spinal Cord Regeneration Study","abstract":"Study of spinal cord regeneration in mice using 10x single cell and spatial techniques.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005032","title":"Genomic Study of Gastric Cancer","description":"We perform whole exome sequencing of 50 pairs of gastric cancer and matched normal samples","abstract":"We perform whole exome sequencing of 50 pairs of gastric cancer and matched normal samples","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-09T06:19:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005033","title":"The WID-EC test for the detection and risk prediction of endometrial cancer","description":null,"abstract":"The WID-EC-index identifies women with endometrial cancer based on a DNA methylation signature derived from cervical smear samples (a total of 281 endometrial cancer samples were included).","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-09T10:10:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005034","title":"Genome-wide characterization of Kuwaiti Arab Population","description":"All the 620 individuals were genotyped using Illumina HumanOmniExpress arrays for 730,525 SNPs.","abstract":"All the 620 individuals were genotyped using Illumina HumanOmniExpress arrays for 730,525 SNPs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-09T11:02:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005035","title":"HCA_Immune_Adult_CZI_Pan_Immune_Aging_RNA","description":"Multi-tissue immune cell analysis across age","abstract":"The goal of this project is to generate an integrated map of cellular diversity in the human immune system across multiple tissues and the human lifespan. It will provide a resource to study mechanisms of tissue residency and the effects of aging.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005036","title":"LifeLines-DEEP follow-up study","description":null,"abstract":"Second round of follow-up of population-based LifeLines-DEEP cohort.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005037","title":"Exome_profiling_of_Adult_T_ALL__TGS","description":"Targeted pulldown of up to 200 Adult T-ALL diagnosis samples and paired control sample if available","abstract":"Targeted pulldown of up to 200 Adult T-ALL diagnosis samples and paired control sample if available","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005038","title":"Gut metagenome/FR 2002","description":"The main goal of the project is the study the associations between the gut metagenome and human health. The dataset contains data for n=7211 FINRISK 2002 participants who underwent fecal sampling. Demultiplexed shallow shotgun metagenomic sequences were quality filtered and adapter trimmed using Atropos (Didion et al., 2017), and human filtered using Bowtie2 (Langmead and Salzberg, 2012).","abstract":"The main goal of the project is the study the associations between the gut metagenome and human health. The dataset contains data for n=7211 FINRISK 2002 participants who underwent fecal sampling. Demultiplexed shallow shotgun metagenomic sequences were quality filtered and adapter trimmed using Atropos (Didion et al., 2017), and human filtered using Bowtie2 (Langmead and Salzberg, 2012).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-11T10:20:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005039","title":"SINGLE-CELL RNA SEQUENCING Single-cell RNA sequencing was performed on 13 ‘mild-moderate’ and 10 ‘critical’ COVID19 PBMC samples","description":"Summary\nEpidemiological and clinical reports have indicated that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we performed cytokine and multiplex immune profiling in mild-moderate and critically ill COVID-19 patients. Hypercytokinemia in COVID-19 differed from the IFN-γ-driven cytokine storm in macrophage activation syndrome, and was more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling showed that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Expression of antigen presenting machinery was also reduced in critical disease.  Furthermore, we found that neutrophils contributed to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together these findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.","abstract":"Summary\nEpidemiological and clinical reports have indicated that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we performed cytokine and multiplex immune profiling in mild-moderate and critically ill COVID-19 patients. Hypercytokinemia in COVID-19 differed from the IFN-γ-driven cytokine storm in macrophage activation syndrome, and was more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling showed that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Expression of antigen presenting machinery was also reduced in critical disease.  Furthermore, we found that neutrophils contributed to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together these findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-11T12:17:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005040","title":"A rare CTSC mutation in Papillon-Lefèvre Syndrome","description":"Papillon-Lefèvre Syndrome (PLS) is an autosomal recessive monogenic disease caused by loss-of-function mutations in the CTSC gene. In this study we performed whole genome sequencing on two siblings, with the PLS-typical symptoms. After sequencing the CTSC gene was analyzed to confirm the PLS diagnosis genetically.","abstract":"Papillon-Lefèvre Syndrome (PLS) is an autosomal recessive monogenic disease caused by loss-of-function mutations in the CTSC gene. In this study we performed whole genome sequencing on two siblings, with the PLS-typical symptoms. After sequencing the CTSC gene was analyzed to confirm the PLS diagnosis genetically.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-11T13:25:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005041","title":"Transcriptome analysis of PBMCs from patients with STAT1 activating mutation","description":null,"abstract":"The transcriptome of peripheral blood cells (PBMCs) from control or patients with an activation mutation on the STAT1 gene was analyzed. \nThis analysis aimed to identify the major changes in the circulating immune cells of patients with STAT1 mutation and compare this with the result of the perturbation prediction tool huva (human variation, R).\nPBMCs were prepared by density centrifugation and cultured ex vivo for 4 hours in RPMI prior to total RNA extraction.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-11T17:11:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005042","title":"Test Study for EGA using data from 1000 Genomes Project - Phase 3","description":"The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes &gt;99% of SNP variants with a frequency of &gt;1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies...","abstract":"The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes &gt;99% of SNP variants with a frequency of &gt;1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies...","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-11T18:07:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005043","title":"hereditary BrEAst Case CONtrol study","description":"The BEACCON study aimed to address the lack of power of previous studies to identify novel BC predisposition genes by performing extensive sequencing in 12,000 women (11,511 analysed following exclusions) and further enhancing power by using an ‘extreme phenotype’ design with enrichment of familial non-BRCA1 and BRCA2 cases, compared with a control population of older women with ongoing confirmation of cancer-free status at June 2019. Three-quarters of the 1303 candidate genes screened were selected based on empiric evidence from local (69 multi-case BC families) or international whole exome sequencing studies, and the remainder were included to provide detailed coverage of functional pathways with established associations with BC","abstract":"The BEACCON study aimed to address the lack of power of previous studies to identify novel BC predisposition genes by performing extensive sequencing in 12,000 women (11,511 analysed following exclusions) and further enhancing power by using an ‘extreme phenotype’ design with enrichment of familial non-BRCA1 and BRCA2 cases, compared with a control population of older women with ongoing confirmation of cancer-free status at June 2019. Three-quarters of the 1303 candidate genes screened were selected based on empiric evidence from local (69 multi-case BC families) or international whole exome sequencing studies, and the remainder were included to provide detailed coverage of functional pathways with established associations with BC","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-11T19:36:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005044","title":"Single-cell roadmap of immune cell responses in chronic myeloid leukemia","description":"To study the innate and adaptive immune responses in CML, we profiled 25 samples from CML patients including samples at diagnosis (n = 7, N = 9, where n is the number of subjects and N the number of samples if different from n) and before and after TKI-cessation with imatinib (n = 6, N = 15) with paired single-cell RNA and T cell receptor (TCR) αβ chain sequencing (scRNA+TCRαβ-seq) and compared our data to different cancers (n = 29) and healthy donors (n = 7). This dataset contains the samples from before and after TKI-cessation, please see the manuscript for info related to the other datasets.","abstract":"To study the innate and adaptive immune responses in CML, we profiled 25 samples from CML patients including samples at diagnosis (n = 7, N = 9, where n is the number of subjects and N the number of samples if different from n) and before and after TKI-cessation with imatinib (n = 6, N = 15) with paired single-cell RNA and T cell receptor (TCR) αβ chain sequencing (scRNA+TCRαβ-seq) and compared our data to different cancers (n = 29) and healthy donors (n = 7). This dataset contains the samples from before and after TKI-cessation, please see the manuscript for info related to the other datasets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-11T19:40:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005045","title":"The DNA methylome of cervical cells and risk of ovarian cancer","description":null,"abstract":"The WID-OC-index identifies women with ovarian cancer based on a DNA methylation signature derived from cervical smear samples (a total of 289 ovarian cancer samples were included)","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-12T12:00:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005046","title":"Using de novo assembly to identify structural variation of complex immune system gene regions","description":"Driven by the necessity to survive environmental pathogens, the human immune system has evolved exceptional diversity and plasticity.  Several factors contribute to this including inheritable structural polymorphism of the underlying genes. To investigate this we generated data for a single healthy European individual (identified as HV31) using multiple long-read (PacBio Sequel II and Oxford Nanopore), short-read (Illumina HiSeq and MGI G400) and linked-read (10X Chromium and stLFR) sequencing platforms, and optical mapping using the Bionano Saphyr platform.  DNA was extracted from monocytes or from peripheral blood mononuclear cells.  We used these data to assemble a set of regions encoding components of the immune system and to investigate structural variation.  The raw data and analysis results are deposited here for generate research use.  A complete description of these data and results can be found in the accompanying article at https://doi.org/10.1101/2021.02.03.429586.","abstract":"Driven by the necessity to survive environmental pathogens, the human immune system has evolved exceptional diversity and plasticity.  Several factors contribute to this including inheritable structural polymorphism of the underlying genes. To investigate this we generated data for a single healthy European individual (identified as HV31) using multiple long-read (PacBio Sequel II and Oxford Nanopore), short-read (Illumina HiSeq and MGI G400) and linked-read (10X Chromium and stLFR) sequencing platforms, and optical mapping using the Bionano Saphyr platform.  DNA was extracted from monocytes or from peripheral blood mononuclear cells.  We used these data to assemble a set of regions encoding components of the immune system and to investigate structural variation.  The raw data and analysis results are deposited here for generate research use.  A complete description of these data and results can be found in the accompanying article at https://doi.org/10.1101/2021.02.03.429586.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-12T13:41:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005047","title":"Single-cell TCR sequencing of gluten-specific T cells from 20  celiac disease patients uploaded on 2021","description":"To examine the T-cell receptors of the gluten-specific T cells in celiac disease, we isolated single CD4+ T cells from blood , gut biopsies  or T-cell lines generated from gut biopsies  using HLA-DQ2.5 tetramers and determined the sequences of rearranged TCRalpha and TCRbeta gene pairs.","abstract":"To examine the T-cell receptors of the gluten-specific T cells in celiac disease, we isolated single CD4+ T cells from blood , gut biopsies  or T-cell lines generated from gut biopsies  using HLA-DQ2.5 tetramers and determined the sequences of rearranged TCRalpha and TCRbeta gene pairs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-12T13:43:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005048","title":"Detection of low-frequency DNA variants by targeted sequencing of the Watson and Crick strands","description":"Identification and quantification of low-frequency mutations remain challenging despite improvements in the baseline error rate of next-generation sequencing technologies. Here, we describe a method, termed SaferSeqS, that addresses this challenge by (1) efficiently introducing identical molecular barcodes in the Watson and Crick strands of template molecules and (2) enriching target sequences with strand-specific PCR. The method achieves high sensitivity and specificity and detects variants at frequencies below 1 in 100,000 DNA template molecules with a background mutation rate of &lt;5 × 10-7 mutants per base pair (bp). We demonstrate that it can evaluate mutations in a single amplicon or simultaneously in multiple amplicons, assess limited quantities of cell-free DNA with high recovery of both strands and reduce the error rate of existing PCR-based molecular barcoding approaches by &gt;100-fold.","abstract":"Identification and quantification of low-frequency mutations remain challenging despite improvements in the baseline error rate of next-generation sequencing technologies. Here, we describe a method, termed SaferSeqS, that addresses this challenge by (1) efficiently introducing identical molecular barcodes in the Watson and Crick strands of template molecules and (2) enriching target sequences with strand-specific PCR. The method achieves high sensitivity and specificity and detects variants at frequencies below 1 in 100,000 DNA template molecules with a background mutation rate of &lt;5 × 10-7 mutants per base pair (bp). We demonstrate that it can evaluate mutations in a single amplicon or simultaneously in multiple amplicons, assess limited quantities of cell-free DNA with high recovery of both strands and reduce the error rate of existing PCR-based molecular barcoding approaches by &gt;100-fold.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-12T16:17:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005049","title":"Combining dasatinib and IFN-α in CML – immunomodulatory effects linked to treatment response and adverse events","description":"We pooled 100,000 cells from the 12 scRNA+TCRab-seq samples from peripheral blood from three time points (n=4, samples at 0, 3, and 12 months) to understand the landscape of immune subsets in CML during the course of dasatinib+IFN-α treatment","abstract":"We pooled 100,000 cells from the 12 scRNA+TCRab-seq samples from peripheral blood from three time points (n=4, samples at 0, 3, and 12 months) to understand the landscape of immune subsets in CML during the course of dasatinib+IFN-α treatment","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-13T09:58:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005050","title":"UROMOL 2020 - RNA-seq data for validation","description":"Total RNAseq data from 47 patients with NMIBC.","abstract":"Total RNAseq data from 47 patients with NMIBC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-15T11:30:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005051","title":"Bone marrow derived stromal cells from Myelodysplastic Syndromes","description":"In this study we performed exome sequencing of bone marrow derived, in-vitro\nexpanded mesenchymal stromal cells from patients with Myelodysplastic\nSyndromes in order to assess clonal mutations in the non hematopoietic\ncompartment. We used bone marrow mononuclear cells as germline controls.\nValidation was carried out with amplicon based resequencing. Alongside we\nprovide RNA Sequencing of MDS and healthy MSCs.","abstract":"In this study we performed exome sequencing of bone marrow derived, in-vitro\nexpanded mesenchymal stromal cells from patients with Myelodysplastic\nSyndromes in order to assess clonal mutations in the non hematopoietic\ncompartment. We used bone marrow mononuclear cells as germline controls.\nValidation was carried out with amplicon based resequencing. Alongside we\nprovide RNA Sequencing of MDS and healthy MSCs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-15T13:54:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005052","title":"Whole-genome sequencing of a census-based elderly cohort of Brazilians","description":null,"abstract":"This project generated a high-coverage WGS dataset of 1,000+ highly admixed elderly from a census-based cohort from São Paulo, Brazil (SABE Study). Current Brazilian population results from admixture of Iberian Europeans, West and East Africans and Native Americans, and from 19th century onwards other groups from Europe, Asian and Middle East arrived in Brazil. The phase 1 includes BAM files from 1,171 individuals, described in pre-print \"Whole-genome sequencing of 1,171 elderly admixed individuals from the largest Latin American metropolis (São Paulo, Brazil)\" (DOI: 10.1101/2020.09.15.298026).","study_type":"Whole Genome Sequencing","pubmed_ids":[28332257],"external_links":null,"is_released":true,"released_date":"2021-02-15T18:14:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005053","title":"Hermansky-Pudlak syndrome type 1 causes impaired anti-microbial immunity  through a pathogenic lipid metabolism-mTOR circuit","description":"Mendelian diseases that present with immune-mediated disorders can provide insights into the molecular mechanisms that drive inflammation. Hermansky-Pudlak syndrome (HPS) types 1 and 4 are caused by defective vesicle trafficking involving the BLOC-3 complex. The presence of inflammatory complications such as Crohn’s disease-like inflammation and lung fibrosis in these patients remains enigmatic. Using mass cytometry we observe an augmented inflammatory monocyte compartment in HPS1 patient peripheral blood that may be associated with a TNF - and IL-1α-dominated cytokine dysregulation. HPS1 patient monocyte-derived macrophages express an inflammatory TNF-OSM mRNA gene signature and changes in lipid metabolism. Using stimulation experiments and lysosomal proteomics we show that defective lipid metabolism drives RAB32-dependent mTOR signaling, facilitated by the accumulation of mTOR on lysosomes. This pathogenic circuit translates into aberrant bacterial clearance, which can be rescued with mTORC1 inhibition. We reveal that a pathogenic lipid-mTOR signaling circuit acts as a metabolic checkpoint for defective anti-microbial activity. This mechanism may be relevant to the complex pathology of HPS1 patients featuring macrophage lipid accumulation, granuloma formation, defective anti-microbial activity and tissue inflammation. Lastly, this circuit may be present in a wider group of disorders with defective lipid metabolism and cholesterol accumulation.","abstract":"Mendelian diseases that present with immune-mediated disorders can provide insights into the molecular mechanisms that drive inflammation. Hermansky-Pudlak syndrome (HPS) types 1 and 4 are caused by defective vesicle trafficking involving the BLOC-3 complex. The presence of inflammatory complications such as Crohn’s disease-like inflammation and lung fibrosis in these patients remains enigmatic. Using mass cytometry we observe an augmented inflammatory monocyte compartment in HPS1 patient peripheral blood that may be associated with a TNF - and IL-1α-dominated cytokine dysregulation. HPS1 patient monocyte-derived macrophages express an inflammatory TNF-OSM mRNA gene signature and changes in lipid metabolism. Using stimulation experiments and lysosomal proteomics we show that defective lipid metabolism drives RAB32-dependent mTOR signaling, facilitated by the accumulation of mTOR on lysosomes. This pathogenic circuit translates into aberrant bacterial clearance, which can be rescued with mTORC1 inhibition. We reveal that a pathogenic lipid-mTOR signaling circuit acts as a metabolic checkpoint for defective anti-microbial activity. This mechanism may be relevant to the complex pathology of HPS1 patients featuring macrophage lipid accumulation, granuloma formation, defective anti-microbial activity and tissue inflammation. Lastly, this circuit may be present in a wider group of disorders with defective lipid metabolism and cholesterol accumulation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-15T18:56:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005054","title":"Genetic analysis of HLA and immune escape genes in Diffuse Large B-cell Lymphoma","description":"Fifty percent of diffuse large B-cell lymphoma (DLBCL) cases lack cell-surface expression of the class-I major histocompatibility complex (MHC-I), thereby escaping immune recognition by cytotoxic T cells. In order to comprehensively identify the mechanisms involved in MHC-I loss, we first performed immunophenotypic analysis of both MHC class-I and -II in 657 cases across the spectrum of B-NHL, revealing that loss of MHC-I, but not MHC-II, is preferentially restricted to DLBCL. We then used whole exome and targeted deep-sequencing to examine genes involved in MHC-I expression in 74 DLBCL samples representative of MHC-I positive and negative cases. We show here that somatic biallelic or monoallelic inactivation of B2M and/or HLA-I is present in 80.9% (34/42) of MHC-I negative tumors. Furthermore, 68.8% (22/32) of MHC-I positive DLBCLs also harbored monoallelic HLA-I genetic alterations (MHC-I positivemono) that lead to allelic imbalance, suggesting allele-specific inactivation. Both MHC-I negative and MHC-I positivemono cases showed a significantly higher mutational burden as well as a higher number of inferred neo-antigens, suggesting co-selection of HLA-I loss and sustained neo-antigen production. Interestingly, the analysis of &amp;gt; 500.000  individuals in two databases revealed homozygosity of germline HLA-I genes in 26-38% of DLBCL patients, a frequency significantly higher than that observed in any other cancer type. In mice, germinal-center B cells lacking HLA-I expression did not progress to lymphoma and were counterselected in the context of oncogene-driven lymphomagenesis, suggesting that additional events are needed to license immune evasion. These results suggest a multi-step process of HLA-I loss including both germ-line and somatic events in DLBCL development, and have direct implications for the pathogenesis and immunotherapeutic targeting of this disease.","abstract":"Fifty percent of diffuse large B-cell lymphoma (DLBCL) cases lack cell-surface expression of the class-I major histocompatibility complex (MHC-I), thereby escaping immune recognition by cytotoxic T cells. In order to comprehensively identify the mechanisms involved in MHC-I loss, we first performed immunophenotypic analysis of both MHC class-I and -II in 657 cases across the spectrum of B-NHL, revealing that loss of MHC-I, but not MHC-II, is preferentially restricted to DLBCL. We then used whole exome and targeted deep-sequencing to examine genes involved in MHC-I expression in 74 DLBCL samples representative of MHC-I positive and negative cases. We show here that somatic biallelic or monoallelic inactivation of B2M and/or HLA-I is present in 80.9% (34/42) of MHC-I negative tumors. Furthermore, 68.8% (22/32) of MHC-I positive DLBCLs also harbored monoallelic HLA-I genetic alterations (MHC-I positivemono) that lead to allelic imbalance, suggesting allele-specific inactivation. Both MHC-I negative and MHC-I positivemono cases showed a significantly higher mutational burden as well as a higher number of inferred neo-antigens, suggesting co-selection of HLA-I loss and sustained neo-antigen production. Interestingly, the analysis of &amp;gt; 500.000  individuals in two databases revealed homozygosity of germline HLA-I genes in 26-38% of DLBCL patients, a frequency significantly higher than that observed in any other cancer type. In mice, germinal-center B cells lacking HLA-I expression did not progress to lymphoma and were counterselected in the context of oncogene-driven lymphomagenesis, suggesting that additional events are needed to license immune evasion. These results suggest a multi-step process of HLA-I loss including both germ-line and somatic events in DLBCL development, and have direct implications for the pathogenesis and immunotherapeutic targeting of this disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-15T21:57:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005055","title":"The WID-BC-index identifies women with primary poor prognostic breast cancer based on DNA methylation in cervical samples","description":"A surrogate marker based on the epigenome that captures these components in easily accessible epithelial tissue could potentially identify women at risk. The WID-BC-index identifies women with breast cancer based on a DNA methylation signature derived from cervical smear samples.","abstract":"A surrogate marker based on the epigenome that captures these components in easily accessible epithelial tissue could potentially identify women at risk. The WID-BC-index identifies women with breast cancer based on a DNA methylation signature derived from cervical smear samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-16T09:48:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005056","title":"CACTUS: integrating clonal architecture with genomic clustering and transcriptome profiling of single tumor cells","description":null,"abstract":"Background: Drawing genotype-to-phenotype maps in tumors is of paramount\n    importance for understanding tumor heterogeneity. Assignment of single cells to\n    their tumor clones of origin can be approached by matching the genotypes of the\n    clones to the mutations found in RNA sequencing of the cells. The condence of\n    the cell-to-clone mapping can be increased by accounting for additional\n    measurements. Follicular lymphoma, a malignancy of mature B cells that\n    continuously acquire mutations in parallel in the exome and in B-cell receptor\n    loci, presents a unique opportunity to join exome-derived mutations with B-cell\n    receptor sequences as independent sources of evidence for clonal evolution.\n    Methods: Here, we propose CACTUS, a probabilistic model that leverages the\n    information from an independent genomic clustering of cells and exploits the\n    scarce single cell RNA sequencing data to map single cells to given imperfect\n    genotypes of tumor clones.\n    Results: We apply CACTUS to two follicular lymphoma patient samples,\n    integrating three measurements: whole exome, single cell RNA, and B-cell\n    receptor sequencing. CACTUS outperforms a predecessor model by condently\n    assigning cells and B-cell receptor-based clusters to the tumor clones.\n    Conclusions: The integration of independent measurements increases model\n    certainty and is the key to improving model performance in the challenging task\n    of charting the genotype-to-phenotype maps in tumors. CACTUS opens the\n    avenue to study the functional implications of tumor heterogeneity, and origins of\n    resistance to targeted therapies. CACTUS is written in R and source code, along\n    with all supporting files, are available on GitHub.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005057","title":"Characterization of DLBCL with a PMBL gene expression signature","description":"Primary mediastinal large B-cell lymphoma (PMBL) is a type of aggressive B-cell lymphoma that typicallyaffects young adults, characterized by presence of a bulky anterior mediastinal mass. Lymphomas withgene expression features of PMBL have been described in non-mediastinal sites, raising questions abouthow these tumors should be classified.Here, we investigated whether these \"non-mediastinal PMBLs\" are indeed PMBLs or instead represent adistinct group within DLBCL. From a cohort of 325 de novo DLBCL cases, we identified tumors frompatients without evidence of anterior mediastinal involvement that expressed a PMBL expression signature(nm-PMBLsig-pos, n=16, 5%). The majority of these tumors expressed MAL and CD23 – proteins typicallyobserved in bona fide PMBL (bf-PMBL). Evaluation of clinical features of nm-PMBLsig-pos cases revealedclose associations with DLBCL, and the majority displayed a germinal center B-cell-like cell-of-origin(GCB). In contrast to bf-PMBL, nm-PMBLsig-pos patients presented at an older age, did not show pleuraldisease, and bone/bone marrow involvement was observed in three cases. However, while clinicallydistinct from bf-PMBL, nm-PMBL-sig-pos tumors resembled bf-PMBL at the molecular level with upregulationof immune response, JAK-STAT, and NF-kB signatures. Mutational analysis revealed frequent somatic genemutations in SOCS1, IL4R, ITPKB and STAT6, as well as CD83 and BIRC3, with the latter genes beingsignificantly more frequently affected than in GCB-DLBCL and bf-PMBL.Our data establish nm-PMBLsig-pos lymphomas as a group of DLBCL with distinct phenotypic and geneticfeatures, and potential implications for gene expression- and mutation-based subtyping of aggressive Bcell lymphoma and related targeted therapies.","abstract":"Primary mediastinal large B-cell lymphoma (PMBL) is a type of aggressive B-cell lymphoma that typicallyaffects young adults, characterized by presence of a bulky anterior mediastinal mass. Lymphomas withgene expression features of PMBL have been described in non-mediastinal sites, raising questions abouthow these tumors should be classified.Here, we investigated whether these \"non-mediastinal PMBLs\" are indeed PMBLs or instead represent adistinct group within DLBCL. From a cohort of 325 de novo DLBCL cases, we identified tumors frompatients without evidence of anterior mediastinal involvement that expressed a PMBL expression signature(nm-PMBLsig-pos, n=16, 5%). The majority of these tumors expressed MAL and CD23 – proteins typicallyobserved in bona fide PMBL (bf-PMBL). Evaluation of clinical features of nm-PMBLsig-pos cases revealedclose associations with DLBCL, and the majority displayed a germinal center B-cell-like cell-of-origin(GCB). In contrast to bf-PMBL, nm-PMBLsig-pos patients presented at an older age, did not show pleuraldisease, and bone/bone marrow involvement was observed in three cases. However, while clinicallydistinct from bf-PMBL, nm-PMBL-sig-pos tumors resembled bf-PMBL at the molecular level with upregulationof immune response, JAK-STAT, and NF-kB signatures. Mutational analysis revealed frequent somatic genemutations in SOCS1, IL4R, ITPKB and STAT6, as well as CD83 and BIRC3, with the latter genes beingsignificantly more frequently affected than in GCB-DLBCL and bf-PMBL.Our data establish nm-PMBLsig-pos lymphomas as a group of DLBCL with distinct phenotypic and geneticfeatures, and potential implications for gene expression- and mutation-based subtyping of aggressive Bcell lymphoma and related targeted therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-17T21:27:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005058","title":"abcdeXXX","description":"abcdeXXX","abstract":"abcdeXXX","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005059","title":"Oncogenic Ectodomain deletion of FGFR1 caused by Breakage-Fusion-Bridges in Squamous Cell lung Cancer","description":"The identification of recurrent 8p11.23 amplifications including FGFR1 raised the hope of a treatable target in squamous cell lung cancer (SQLC). However, only a minority of patients with FGFR1-amplified tumors respond to single agent inhibitor therapy targeting FGFR. To understand the underlying mechanism of FGFR1 dependency, we performed whole genome and transcriptome sequencing of 25 FGFR1-amplified primary tumors with unknown response upon FGFR inhibition. In addition, we performed deep sequencing of 26 FGFR1-amplified samples whereof the response upon FGFR inhibition was known for 25 samples. In both cohorts we identified intra-chromosomal tail-to-tail breaks close to the FGFR1 transcription start site, being responsible for focal amplification of FGFR1. These specific breaks are caused by a Breakage-Fusion-Bridge-like (BFB-like) mechanism. Here, we associate these breaks with FGFR inhibitor sensitivity. Moreover, in some cases these breaks are located within the open reading frame of FGFR1, which leads to the expression of an ΔEC-FGFR1 transcript that lacks the ecto-domain. Overexpression of ΔEC-FGFR1 transforms Baf3 cells and lead to an FGFR1-dependent phenotype. Our results demonstrate that the truncation of the FGFR1 ectodomain is a frequent event in 8p11.23-amplified squamous cell lung cancer caused by tail-to-tail breaks. These breaks might be used as a predictive therapeutic marker to stratify patients for FGFR-inhibitor therapy.","abstract":"The identification of recurrent 8p11.23 amplifications including FGFR1 raised the hope of a treatable target in squamous cell lung cancer (SQLC). However, only a minority of patients with FGFR1-amplified tumors respond to single agent inhibitor therapy targeting FGFR. To understand the underlying mechanism of FGFR1 dependency, we performed whole genome and transcriptome sequencing of 25 FGFR1-amplified primary tumors with unknown response upon FGFR inhibition. In addition, we performed deep sequencing of 26 FGFR1-amplified samples whereof the response upon FGFR inhibition was known for 25 samples. In both cohorts we identified intra-chromosomal tail-to-tail breaks close to the FGFR1 transcription start site, being responsible for focal amplification of FGFR1. These specific breaks are caused by a Breakage-Fusion-Bridge-like (BFB-like) mechanism. Here, we associate these breaks with FGFR inhibitor sensitivity. Moreover, in some cases these breaks are located within the open reading frame of FGFR1, which leads to the expression of an ΔEC-FGFR1 transcript that lacks the ecto-domain. Overexpression of ΔEC-FGFR1 transforms Baf3 cells and lead to an FGFR1-dependent phenotype. Our results demonstrate that the truncation of the FGFR1 ectodomain is a frequent event in 8p11.23-amplified squamous cell lung cancer caused by tail-to-tail breaks. These breaks might be used as a predictive therapeutic marker to stratify patients for FGFR-inhibitor therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005060","title":"SARS-CoV-2 escapes CD8 T cell surveillance via mutations in MHC-I restricted epitopes [10x]","description":"CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control. Here, we identified non-synonymous mutations in MHC-I restricted CD8+ T cell epitopes after deep sequencing of 747 SARS-CoV-2 virus isolates. Mutant peptides exhibited diminished or abrogated MHC-I binding, which was associated with a loss of recognition and functional responses by CD8+ T cells isolated from HLA-matched COVID-19 patients. Our findings highlight the capacity of SARS-CoV-2 to subvert CD8+ T cell surveillance through sporadically emerging escape mutations in MHC- I restricted viral epitopes.","abstract":"CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control. Here, we identified non-synonymous mutations in MHC-I restricted CD8+ T cell epitopes after deep sequencing of 747 SARS-CoV-2 virus isolates. Mutant peptides exhibited diminished or abrogated MHC-I binding, which was associated with a loss of recognition and functional responses by CD8+ T cells isolated from HLA-matched COVID-19 patients. Our findings highlight the capacity of SARS-CoV-2 to subvert CD8+ T cell surveillance through sporadically emerging escape mutations in MHC- I restricted viral epitopes.","study_type":"Other","pubmed_ids":[33664060],"external_links":null,"is_released":true,"released_date":"2021-02-18T19:26:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005061","title":"Stromal cell diversity associated with immune evasion in human triple‐negative breast cancer","description":null,"abstract":"The tumour stroma regulates nearly all stages of carcinogenesis. Stromal heterogeneity in human triple-negative breast cancers (TNBCs) remains poorly understood, limiting the development of stromal-targeted therapies. Single-cell RNA sequencing of five TNBCs revealed two cancer-associated fibroblast (CAF) and two perivascular-like (PVL) subpopulations. CAFs clustered into two states: the first with features of myofibroblasts and the second characterised by high expression of growth factors and immunomodulatory molecules. PVL cells clustered into two states consistent with a differentiated and immature phenotype. We showed that these stromal states have distinct morphologies, spatial relationships and functional properties in regulating the extracellular matrix. Using cell signalling predictions, we provide evidence that stromal-immune crosstalk acts via a diverse array of immunoregulatory molecules. Importantly, the investigation of gene signatures from inflammatory-CAFs and differentiated-PVL cells in independent TNBC patient cohorts revealed strong associations with cytotoxic T-cell dysfunction and exclusion, respectively. Such insights present promising candidates to further investigate for new therapeutic strategies in the treatment of TNBCs.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-18T23:52:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005062","title":"Comparison of next generation sequencing, droplet digital PCR, and quantitative real-time PCR for the earlier detection and quantification of HPV in HPV-positive oropharyngeal cancer","description":"We directly compared next generation sequencing (NGS), droplet digital PCR (ddPCR), and quantitative real-time PCR (qPCR) for their ability to detect HPV16 DNA in plasma and oral rinse from 66 patients diagnosed with HPV16-positive oropharyngeal cancer (HPV16-OPC). HPV DNA detection by NGS and ddPCR in plasma samples both had good sensitivity (70%) for HPV16-OPC compared to 20.6% sensitivity by qPCR (p &lt; 0.001). In oral rinse, NGS demonstrated a superior sensitivity of 75.0% as compared to both ddPCR (8.3%, p &lt; 0.001) and qPCR (2.1%, p &lt; 0.001). HPV levels detected in plasma by NGS but not ddPCR or qPCR may mirror the clinical course of HPV-16-OPC.","abstract":"We directly compared next generation sequencing (NGS), droplet digital PCR (ddPCR), and quantitative real-time PCR (qPCR) for their ability to detect HPV16 DNA in plasma and oral rinse from 66 patients diagnosed with HPV16-positive oropharyngeal cancer (HPV16-OPC). HPV DNA detection by NGS and ddPCR in plasma samples both had good sensitivity (70%) for HPV16-OPC compared to 20.6% sensitivity by qPCR (p &lt; 0.001). In oral rinse, NGS demonstrated a superior sensitivity of 75.0% as compared to both ddPCR (8.3%, p &lt; 0.001) and qPCR (2.1%, p &lt; 0.001). HPV levels detected in plasma by NGS but not ddPCR or qPCR may mirror the clinical course of HPV-16-OPC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005063","title":"Exome sequencing data on patient D:II-1","description":null,"abstract":"Background: Inherited defects in the base excision repair (BER) pathway predispose to adenomatous polyposis and colorectal cancer (CRC), but only explain a minority of such cases. \nMethods: We performed whole-genome sequencing of germline DNA from 35 individuals with multiple colorectal adenomas of no identifiable genetic aetiology. We obtained detailed clinical, histological and molecular information from tumours of selected patients. \nResults: We identified a patient with a homozygous loss-of-function (LOF) germline variant in MBD4, which encodes a BER glycosylase that repairs G:T mismatches resulting from deaminated 5’-methylcytosine. This patient developed myelodysplasia (MDS) and acute myeloid leukaemia (AML) subsequent to polyposis. Two of three previously described AML patients with biallelic germline LOF MBD4 variants also had a history of colorectal polyps, albeit of unknown significance at time of diagnosis. A significant excess of somatic CpG&gt;TpG mutations, closely resembling COSMIC mutational signature SBS1v3, was found in all adenomas and AMLs from two available MBD4-deficient patients. Compared to sporadic CRCs, MBD4-deficient adenomas harboured mutations in similar driver genes, although AMER1 mutations were more common and KRAS mutations less frequent. Targeted analyses of MBD4 in 1,860 individuals with polyposis and/or CRC found no clear evidence that monoallelic LOF MBD4 variants conferred a risk of colorectal tumours.  \nConclusion: Biallelic germline LOF MBD4 variants predispose to a rare syndrome characterized by multiple adenomatous colorectal polyps and MDS/AML. We suggest that this condition should be termed MBD4-associated neoplasia syndrome (MANS) and that MBD4 is included in panel tests for the genetic diagnosis of polyposis and/or early-onset AML.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005064","title":"Mutational analysis of an oligoprogressive sarcomatoid hepatocellular carcinoma treated with an immune checkpoint inhibitor.","description":"In this study, we describe a patient diagnosed with metastatic sarcomatoid hepatocellular carcinoma that showed a remarkable tumor response to Nivolumab, an immune checkpoint inhibitor, followed by an oligoprogression. Molecular analysis of the primary tumor in addition to a bone and brain metastasis was performed and we were able to identify driver genetic alterations indicating a possible role in the tumorigenesis process besides some alterations that may be associated with metastasis.","abstract":"In this study, we describe a patient diagnosed with metastatic sarcomatoid hepatocellular carcinoma that showed a remarkable tumor response to Nivolumab, an immune checkpoint inhibitor, followed by an oligoprogression. Molecular analysis of the primary tumor in addition to a bone and brain metastasis was performed and we were able to identify driver genetic alterations indicating a possible role in the tumorigenesis process besides some alterations that may be associated with metastasis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-19T15:49:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005065","title":"Genomic Landscape of Malignant Peripheral Nerve Sheath Tumor-like Melanoma","description":"Malignant peripheral nerve sheath tumor (MPNST)-like melanoma is a rare malignancy with overlapping characteristics of both neural sarcoma and melanoma. The genomics of MPNST-like melanoma have not been previously described. This study provides the results of whole exome and transcriptome sequencing analysis of 8 samples from 6 patients with confirmed diagnosis of MPNST-like melanoma. This study demonstrates that MPNST-like melanoma shares oncogenic alterations common to both cutaneous melanoma and MPNST, and also suggests that MPNST-like melanoma harbors unique genomic and transcriptomic alterations.","abstract":"Malignant peripheral nerve sheath tumor (MPNST)-like melanoma is a rare malignancy with overlapping characteristics of both neural sarcoma and melanoma. The genomics of MPNST-like melanoma have not been previously described. This study provides the results of whole exome and transcriptome sequencing analysis of 8 samples from 6 patients with confirmed diagnosis of MPNST-like melanoma. This study demonstrates that MPNST-like melanoma shares oncogenic alterations common to both cutaneous melanoma and MPNST, and also suggests that MPNST-like melanoma harbors unique genomic and transcriptomic alterations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-19T17:29:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005066","title":"Single-cell RNA-seq data from metastatic ovarian cancer for quality control study","description":"Quality control is a crucial preliminary step in any single-cell RNAseq experiment, where hard thresholds are commonly used. In order to develop a methodology for a more precise cell filtering in the early steps of a scRNAseq data analysis, we collected tissue samples before chemotherapy from 4 patients.","abstract":"Quality control is a crucial preliminary step in any single-cell RNAseq experiment, where hard thresholds are commonly used. In order to develop a methodology for a more precise cell filtering in the early steps of a scRNAseq data analysis, we collected tissue samples before chemotherapy from 4 patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-22T08:00:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005067","title":"Whole_Exome_Sequencing_in_non_syndromic_congenital_heart_patients_and_families_II","description":"Whole Exome Sequencing of Non-syndromic cases of congenital heart defects (CHD)\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Non-syndromic cases of congenital heart defects (CHD) exhibit variable modes of inheritance (Mendelian and non-Mendelian). Several studies using whole exome sequencing (WES) have identified strong candidates in humans. We have conducted a number of studies with collaborators and colleagues to help us understand the diverse genetic architecture of syndromic as well as non-syndromic cases and this has allowed us to clarify further the best approach for the next generation of studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005068","title":"Discovery of cancer prognostic markers based on comparison of gene expression in colorectal cancer samples.","description":"Here, we analyse bulk mRNA-seq data derived from normal tissues adjacent to tumors (NATs) and tumour tissues of colorectal cancer (CRC), including 80 NAT samples and 80 tumour samples.","abstract":"Here, we analyse bulk mRNA-seq data derived from normal tissues adjacent to tumors (NATs) and tumour tissues of colorectal cancer (CRC), including 80 NAT samples and 80 tumour samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-22T12:38:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005069","title":"Sensitive and reproducible cell-free methylome quantification with synthetic spike-in controls","description":null,"abstract":"We designed spike-in controls for cfMeDIP-seq experiments. These spike-in controls mitigate batch effects and allow for absolute quantification of cell-free DNA.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-22T15:20:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005070","title":"Breast tissue methylation analysis","description":null,"abstract":"We aimed to assess breast tissue methylation in breast cancers (triple negative breast cancer) as well as control breast tissue and breast tissue from women with increased breast cancer risk. The dataset includes methylation data from triple negative breast cancer tissue, breast tissue from risk-reducing surgeries (BRCA1/2 mutation carriers), normal breast tissue (cosmetic surgeries) as well as normal tissue adjacent to breast cancers. This dataset also comprises methylation data from controls or BRCA1/2 mutation carriers before and after mifepristone or placebo treatment.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-22T17:37:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005071","title":"Subtype-associated epigenomic landscape and 3D genome structure in bladder cancer","description":"We determine the genome-wide transcriptome, enhancer landscape and transcription factor binding profiles of FOXA1 and GATA3 in luminal and basal subtypes of bladder cancer.   Furthermore, we report the first-ever mapping of genome-wide chromatin interactions by Hi-C in both bladder cancer cell lines and primary patient tumors. We show that subtype-specific transcription is accompanied by specific open chromatin and epigenomic marks, at least partially driven by distinct transcription factor binding at distal-enhancers of luminal and basal bladder cancers. Finally, we identify a novel clinically relevant transcription factor, Neuronal PAS Domain Protein 2 (NPAS2), in luminal bladder cancers that regulates other subtype-specific genes and influences cancer cell proliferation and migration.","abstract":"We determine the genome-wide transcriptome, enhancer landscape and transcription factor binding profiles of FOXA1 and GATA3 in luminal and basal subtypes of bladder cancer.   Furthermore, we report the first-ever mapping of genome-wide chromatin interactions by Hi-C in both bladder cancer cell lines and primary patient tumors. We show that subtype-specific transcription is accompanied by specific open chromatin and epigenomic marks, at least partially driven by distinct transcription factor binding at distal-enhancers of luminal and basal bladder cancers. Finally, we identify a novel clinically relevant transcription factor, Neuronal PAS Domain Protein 2 (NPAS2), in luminal bladder cancers that regulates other subtype-specific genes and influences cancer cell proliferation and migration.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-23T03:41:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005072","title":"Host_RNAseq_Understanding_differences_in_clinical_presentations_of_leishmaniasis_in_an_endemic_disease_focus","description":"This study aims to understand the mechanistic basis of the different clinical presentations of cutaneous\nleishmaniasis (CL) in an endemic focus in North West Ethiopia. These data are RNA-seq transcriptomes of (1) biopsies taken from patient lesions in this focus, or (2) matched whole-blood samples from these patients.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Host RNAseq-Understanding differences in clinical presentations of leishmaniasis in an endemic disease focus","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005073","title":"Whole-exome sequencing of hepatocellular carcinoma biopsies (proteogenomic study)","description":"We performed a proteogenomic analysis of hepatocellular carcinomas (HCCs) across clinical stages and etiologies to define the deregulated pathways and heterogeneity among HCCs. We identified pathways that are differentially regulated on the genomic, transcriptomic, proteomic and phosphoproteomic levels. Integrative clustering identified HCC subgroups that show distinct regulation of biological processes, metabolic reprogramming and kinase activation.","abstract":"We performed a proteogenomic analysis of hepatocellular carcinomas (HCCs) across clinical stages and etiologies to define the deregulated pathways and heterogeneity among HCCs. We identified pathways that are differentially regulated on the genomic, transcriptomic, proteomic and phosphoproteomic levels. Integrative clustering identified HCC subgroups that show distinct regulation of biological processes, metabolic reprogramming and kinase activation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-23T22:40:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005074","title":"Transcriptome sequencing of hepatocellular carcinoma biopsies (proteogenomic study)","description":"We performed a proteogenomic analysis of hepatocellular carcinomas (HCCs) across clinical stages and etiologies to define the deregulated pathways and heterogeneity among HCCs. We identified pathways that are differentially regulated on the genomic, transcriptomic, proteomic and phosphoproteomic levels. Integrative clustering identified HCC subgroups that show distinct regulation of biological processes, metabolic reprogramming and kinase activation.","abstract":"We performed a proteogenomic analysis of hepatocellular carcinomas (HCCs) across clinical stages and etiologies to define the deregulated pathways and heterogeneity among HCCs. We identified pathways that are differentially regulated on the genomic, transcriptomic, proteomic and phosphoproteomic levels. Integrative clustering identified HCC subgroups that show distinct regulation of biological processes, metabolic reprogramming and kinase activation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-23T22:41:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005075","title":"Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia","description":"Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). We comprehensively investigated genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing.","abstract":"Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). We comprehensively investigated genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-24T06:35:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005076","title":"Liverpool Preterm Birth Biomarker Study","description":"Preterm birth is a multifactorial condition defined as birth less than 37 weeks of gestation. This study aimed to identify early pregnancy biomarkers from maternal genome-wide and transcriptome-wide data of women experiencing two types of spontaneous PTB (sPTB): spontaneous preterm birth (SPTB) and preterm premature rupture of membranes (PPROM).  Whole blood samples were obtained from women with singleton pregnancies (N=567) recruited at the Liverpool Women’s Hospital at 16 and 20 weeks of gestation. Women with a previous history of sPTB pregnancies &lt;34 weeks were categorised on their index pregnancy outcome as spontaneous preterm birth (SPTB) and preterm premature rupture of membranes (PPROM) or high-risk term control (HTERM, ≥37 weeks). Women with no history of SPTB/PPROM and delivered at term were LTERM (≥39 weeks of gestation). DNA was genotyped on the UK Biobank Axiom™ array (Applied Biosystems™, Thermo Fisher Scientific) and RNA who processed using the Clariom™ D Human assay (Thermo Fisher Scientific). Genome-wide association analysis, differential expression analysis and expression quantitative trait loci (eQTL) were completed.","abstract":"Preterm birth is a multifactorial condition defined as birth less than 37 weeks of gestation. This study aimed to identify early pregnancy biomarkers from maternal genome-wide and transcriptome-wide data of women experiencing two types of spontaneous PTB (sPTB): spontaneous preterm birth (SPTB) and preterm premature rupture of membranes (PPROM).  Whole blood samples were obtained from women with singleton pregnancies (N=567) recruited at the Liverpool Women’s Hospital at 16 and 20 weeks of gestation. Women with a previous history of sPTB pregnancies &lt;34 weeks were categorised on their index pregnancy outcome as spontaneous preterm birth (SPTB) and preterm premature rupture of membranes (PPROM) or high-risk term control (HTERM, ≥37 weeks). Women with no history of SPTB/PPROM and delivered at term were LTERM (≥39 weeks of gestation). DNA was genotyped on the UK Biobank Axiom™ array (Applied Biosystems™, Thermo Fisher Scientific) and RNA who processed using the Clariom™ D Human assay (Thermo Fisher Scientific). Genome-wide association analysis, differential expression analysis and expression quantitative trait loci (eQTL) were completed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-25T16:53:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005077","title":"Anal SCC cell line and parent tumour comparative whole exome sequencing","description":"1) To perform whole exome sequencing on a panel of five human anal squamous cell carcinoma lines and their respective parent tumours.\n2) To perform a comparative analysis between the lines and their parent tumours.\n3) Specifically assess the somatic nucleotide variants, copy number variants, mutational burden and mutational signatures.","abstract":"1) To perform whole exome sequencing on a panel of five human anal squamous cell carcinoma lines and their respective parent tumours.\n2) To perform a comparative analysis between the lines and their parent tumours.\n3) Specifically assess the somatic nucleotide variants, copy number variants, mutational burden and mutational signatures.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-26T00:39:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005078","title":"The WID-CIN test identifies women with, and at risk of, cervical intraepithelial neoplasia grade 3 and invasive cervical cancer (CIN3+)","description":"We analysed DNA methylation at &gt;850,000 CpG sites across the genome using the Illumina EPIC array in a total of 1,254 cervical liquid-based cytology samples from cases of screen-detected histologically verified CIN1-3+ (98% hrHPV-positive) and population-based control women free from any cervical disease (100% hrHPV-positive). We developed the WID-CIN-test which is a DNA methylation signature consisting of 5,000 CpG sites.","abstract":"We analysed DNA methylation at &gt;850,000 CpG sites across the genome using the Illumina EPIC array in a total of 1,254 cervical liquid-based cytology samples from cases of screen-detected histologically verified CIN1-3+ (98% hrHPV-positive) and population-based control women free from any cervical disease (100% hrHPV-positive). We developed the WID-CIN-test which is a DNA methylation signature consisting of 5,000 CpG sites.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-02-26T15:29:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005079","title":"Multiple migrations to the Philippines during the last 50,000 years","description":null,"abstract":"A key link to understand human history in Island Southeast Asia is the Philippine archipelago and its poorly investigated genetic diversity. We collected and analyzed the most comprehensive set of population-genomic data for the Philippines, 1028 individuals covering 115 indigenous communities. We demonstrate that the Philippines were populated by at least five waves of human migration. The Cordillerans migrated into the Philippines prior to the arrival of rice agriculture, where some remain to be the least admixed East Asians carrying an ancestry shared by all Austronesian-speaking populations; thereby challenging an exclusive Out-of-Taiwan model of joint farming-language-people dispersal.  Altogether, our findings portray Philippines as a crucial gateway, with a multilayered history, that ultimately changed the genetic landscape of the Asia-Pacific region.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005080","title":"Multiple migrations to the Philippines during the last 50,000 years","description":null,"abstract":"A key link to understand human history in Island Southeast Asia is the Philippine archipelago and its poorly investigated genetic diversity. We collected and analyzed the most comprehensive set of population-genomic data for the Philippines, 1028 individuals covering 115 indigenous communities. We demonstrate that the Philippines were populated by at least five waves of human migration. The Cordillerans migrated into the Philippines prior to the arrival of rice agriculture, where some remain to be the least admixed East Asians carrying an ancestry shared by all Austronesian-speaking populations; thereby challenging an exclusive Out-of-Taiwan model of joint farming-language-people dispersal.  Altogether, our findings portray Philippines as a crucial gateway, with a multilayered history, that ultimately changed the genetic landscape of the Asia-Pacific region.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005081","title":"Molecular analysis of inflammatory myofibroblastic tumor (WGS and WES)","description":null,"abstract":"The clinical phase 2 trial EORTC 90101 “CREATE” showed high anti-tumor activity of crizotinib, the inhibitor of anaplastic lymphoma kinase (ALK)/ROS1, in patients with advanced inflammatory myofibroblastic tumor (IMFT). These findings suggested also that molecular targets beyond ALK/ROS1 contribute to the sensitivity to this kinase inhibitor. We therefore performed an in-depth molecular characterization of archival IMFT tissue, collected from patients enrolled in this trial, with the aim to identify other molecular alterations which could play a role in the response to crizotinib.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-01T10:15:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005082","title":"HCA_Skin_Disease_WSSS_DNA_NCL","description":"WSSS Deep dive of diseased human adult skin","abstract":"WSSS Deep dive of diseased human adult skin","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005083","title":"Multiple migrations to the Philippines during the last 50,000 years","description":"A key link to understand human history in Island Southeast Asia is the Philippine archipelago and its poorly investigated genetic diversity. We collected and analyzed the most comprehensive set of population-genomic data for the Philippines, 1028 individuals covering 115 indigenous communities. We demonstrate that the Philippines were populated by at least five waves of human migration. The Cordillerans migrated into the Philippines prior to the arrival of rice agriculture, where some remain to be the least admixed East Asians carrying an ancestry shared by all Austronesian-speaking populations; thereby challenging an exclusive Out-of-Taiwan model of joint farming-language-people dispersal.  Altogether, our findings portray Philippines as a crucial gateway, with a multilayered history, that ultimately changed the genetic landscape of the Asia-Pacific region.","abstract":"A key link to understand human history in Island Southeast Asia is the Philippine archipelago and its poorly investigated genetic diversity. We collected and analyzed the most comprehensive set of population-genomic data for the Philippines, 1028 individuals covering 115 indigenous communities. We demonstrate that the Philippines were populated by at least five waves of human migration. The Cordillerans migrated into the Philippines prior to the arrival of rice agriculture, where some remain to be the least admixed East Asians carrying an ancestry shared by all Austronesian-speaking populations; thereby challenging an exclusive Out-of-Taiwan model of joint farming-language-people dispersal.  Altogether, our findings portray Philippines as a crucial gateway, with a multilayered history, that ultimately changed the genetic landscape of the Asia-Pacific region.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-01T13:27:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005084","title":"Clinical significance of novel subtypes of acute lymphoblastic leukemia in the context of minimal residual disease-directed therapy","description":"We evaluate clinical significance of recently identified subtypes of acute lymphoblastic leukemia (ALL) in 598 children treated with minimal residual disease (MRD)-directed therapy. Among the 16 B-ALL and 8 T-ALL subtypes identified by next generation sequencing, ETV6-RUNX1, high-hyperdiploid and DUX4-rearranged B-ALL had the best five-year event-free survival rates (95% to 98.4%); TCF3-PBX1, PAX5alt, T-cell, ETP, iAMP21, and hypodiploid ALL intermediate rates (80.0% to 88.2%); and BCR-ABL1, BCR-ABL1-like and ETV6-RUNX1-like and KMT2A-rearranged ALL the worst rates (64.1% to 76.2%). All but three of the 142 patients with day-8 blood MRD &lt;0.01% remained in remission. Among new subtypes, intensified therapy based on day-15 MRD≥1% improved outcome of DUX4-rearranged, BCR-ABL1-like, and ZNF384-rearranged ALL, and achievement of day-42 MRD&lt;0.01% did not preclude relapse of PAX5alt, MEF2D-rearranged and ETV6-RUNX1-like ALL. Thus,  new subtypes including DUX4-rearranged, PAX5alt, BCR-ABL1-like, ETV6-RUNX1-like, MEF2D-rearranged and ZNF384-rearranged ALL have important prognostic and therapeutic implications.","abstract":"We evaluate clinical significance of recently identified subtypes of acute lymphoblastic leukemia (ALL) in 598 children treated with minimal residual disease (MRD)-directed therapy. Among the 16 B-ALL and 8 T-ALL subtypes identified by next generation sequencing, ETV6-RUNX1, high-hyperdiploid and DUX4-rearranged B-ALL had the best five-year event-free survival rates (95% to 98.4%); TCF3-PBX1, PAX5alt, T-cell, ETP, iAMP21, and hypodiploid ALL intermediate rates (80.0% to 88.2%); and BCR-ABL1, BCR-ABL1-like and ETV6-RUNX1-like and KMT2A-rearranged ALL the worst rates (64.1% to 76.2%). All but three of the 142 patients with day-8 blood MRD &lt;0.01% remained in remission. Among new subtypes, intensified therapy based on day-15 MRD≥1% improved outcome of DUX4-rearranged, BCR-ABL1-like, and ZNF384-rearranged ALL, and achievement of day-42 MRD&lt;0.01% did not preclude relapse of PAX5alt, MEF2D-rearranged and ETV6-RUNX1-like ALL. Thus,  new subtypes including DUX4-rearranged, PAX5alt, BCR-ABL1-like, ETV6-RUNX1-like, MEF2D-rearranged and ZNF384-rearranged ALL have important prognostic and therapeutic implications.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-01T16:39:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005085","title":"Profiling of H3K27ac landscape in immune cells from rheumatoid arthritis patients and healthy controls","description":"We collected peripheral blood mononuclear cells (PBMC) from 6 RA patients and 4 healthy controls, as well as synovial fluid from the same RA patients. We then sorted B cells, CD4+ and CD8+ T cells, regulatory T cells and monocytes using flow cytometry and profiled regions marked with H3K27ac using CUT&amp;Tag.","abstract":"We collected peripheral blood mononuclear cells (PBMC) from 6 RA patients and 4 healthy controls, as well as synovial fluid from the same RA patients. We then sorted B cells, CD4+ and CD8+ T cells, regulatory T cells and monocytes using flow cytometry and profiled regions marked with H3K27ac using CUT&amp;Tag.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-02T15:28:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005086","title":"ARAF Mutations Confer Resistance to RAF Dimer Inhibitor Belvarafenib in NRAS- and BRAF- Mutant Melanoma","description":"Belvarafenib, a potent and selective RAF dimer (type II) inhibitor, exhibits clinical activity in BRAFV600E- and NRAS-mutant melanoma patients. Here, we report the first-in-human phase I study investigating maximum tolerated dose, assessing safety and preliminary efficacy of belvarafenib in BRAF- and RAS-mutated advanced solid tumors (NCT02405065, NCT03118817). Through generation of belvarafenib resistant NRAS- mutant melanoma cells and analysis of circulating tumor DNA from patients treated with belvarafenib, we identified novel recurrent mutations in ARAF within the kinase domain. ARAF mutants conferred resistance to belvarafenib in both a dimer- and kinase activity- dependent manner. Belvarafenib induced ARAF mutant dimers, and dimers containing mutant ARAF were active in the presence of inhibitor. ARAF mutations may serve as a general resistance mechanism for RAF dimer inhibitors as the mutants exhibit reduced sensitivity to a panel of type II RAF inhibitors. The combination of RAF plus MEK inhibition may be used to delay ARAF-driven resistance and suggests a rational combination for clinical use. Taken together, our findings reveal specific and compensatory functions for the ARAF isoform and implicate ARAF mutations as a driver of resistance to RAF dimer inhibitors.","abstract":"Belvarafenib, a potent and selective RAF dimer (type II) inhibitor, exhibits clinical activity in BRAFV600E- and NRAS-mutant melanoma patients. Here, we report the first-in-human phase I study investigating maximum tolerated dose, assessing safety and preliminary efficacy of belvarafenib in BRAF- and RAS-mutated advanced solid tumors (NCT02405065, NCT03118817). Through generation of belvarafenib resistant NRAS- mutant melanoma cells and analysis of circulating tumor DNA from patients treated with belvarafenib, we identified novel recurrent mutations in ARAF within the kinase domain. ARAF mutants conferred resistance to belvarafenib in both a dimer- and kinase activity- dependent manner. Belvarafenib induced ARAF mutant dimers, and dimers containing mutant ARAF were active in the presence of inhibitor. ARAF mutations may serve as a general resistance mechanism for RAF dimer inhibitors as the mutants exhibit reduced sensitivity to a panel of type II RAF inhibitors. The combination of RAF plus MEK inhibition may be used to delay ARAF-driven resistance and suggests a rational combination for clinical use. Taken together, our findings reveal specific and compensatory functions for the ARAF isoform and implicate ARAF mutations as a driver of resistance to RAF dimer inhibitors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-02T18:19:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005087","title":"Whole exome sequencing from small cell lung cancer patients","description":null,"abstract":"To identify genomic drivers present in limited-stage small cell lung cancer (LS-SCLC); To determine the overall tumor mutational burden in LS-SCLC; To determine genomic intratumor heterogeneity (ITH) in LS-SCLC.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-02T19:34:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005088","title":"HSC_population_dynamics___KX004_samples___methylseq","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005089","title":"HSC_population_dynamics___CB002_samples___methylseq","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005090","title":"A_cell_atlas_of_the_human_fetal_spine_SB_HDBR_Project_200532","description":"A cell atlas of the human fetal spine","abstract":"Establishment of a cell atlas of the human fetal spine using 10x single cell techniques.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-04T09:51:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005091","title":"Enrichment of homologous recombination repair alteration in prostate cancer brain metastases","description":"Whole-exome sequencing profiling of prostate cancer brain metastases","abstract":"Whole-exome sequencing profiling of prostate cancer brain metastases","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-04T10:24:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005092","title":"Enrichment of homologous recombination repair alteration in prostate cancer brain metastases","description":null,"abstract":"Targeted RNA-seq of prostate cancer brain metastases","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005093","title":"single-stranded DNA study","description":"A ssDNA library protocol was applied to cfDNA from plasma samples obtained from different DNA extraction methods and revealed significant differences in DNA fragmentation patterns in comparison to dsDNA-based protocols. In particular, a specific combination of methods revealed a population of ultrashort fragments, organized at ~50 bp. We observed significant differences in the relative abundance of these ultrashort DNA fragments in plasma from healthy individuals and cancer patients. Through shallow whole genome sequencing (sWGS, &lt;0.5-fold coverage) and the analysis of somatic copy number aberrations (SCNA), we determined the landscape of genetic alterations in this newly identified population of cfDNA fragments. In addition, we studied their potential link with regulatory regions by investigating the genome-wide coverage patterns at transcription start sites (TSS). Furthermore, we demonstrated that the ultrashort cfDNA fragments map to regions associated with secondary DNA structures, G-quadruplexes (G4s).","abstract":"A ssDNA library protocol was applied to cfDNA from plasma samples obtained from different DNA extraction methods and revealed significant differences in DNA fragmentation patterns in comparison to dsDNA-based protocols. In particular, a specific combination of methods revealed a population of ultrashort fragments, organized at ~50 bp. We observed significant differences in the relative abundance of these ultrashort DNA fragments in plasma from healthy individuals and cancer patients. Through shallow whole genome sequencing (sWGS, &lt;0.5-fold coverage) and the analysis of somatic copy number aberrations (SCNA), we determined the landscape of genetic alterations in this newly identified population of cfDNA fragments. In addition, we studied their potential link with regulatory regions by investigating the genome-wide coverage patterns at transcription start sites (TSS). Furthermore, we demonstrated that the ultrashort cfDNA fragments map to regions associated with secondary DNA structures, G-quadruplexes (G4s).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-04T12:42:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005094","title":"Oncogenic mutations and gene fusions in CD30-positive lymphoproliferations and clonally related mycosis fungoides occurring in the same patients","description":null,"abstract":"We analyzed the molecular profile of 16 samples of two patients suffering both from CD30-positive LPD and MF being obtained over a time course of at least 5 years. By targeted sequencing technologies we detected oncogenic fusions afflicting the JAK/STAT signaling pathway in lesions of MF and LyP in both patients. Additional STAT5A mutations exclusively occurred in lesions of CD30-positive LPD in one patient","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005095","title":"The_evolution_of_CML","description":"This project aims to investigate the timing of acquistion of key driver events in CML such as the canonical BCR/ABL gene fusion and their clonal trajectories in order determine selection advantage of such clones. Colonies derived from single haematopoietic progenitors will be sequenced as clonal units. This is in line with other work in the Nangalia lab and CASM.","abstract":"This project aims to investigate the timing of acquistion of key driver events in CML such as the canonical BCR/ABL gene fusion and their clonal trajectories in order determine selection advantage of such clones. Colonies derived from single haematopoietic progenitors will be sequenced as clonal units. This is in line with other work in the Nangalia lab and CASM.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-04T16:43:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005096","title":"Whole genome sequencing of 76 tumor and normal samples from 11 SI-NET patients","description":"We have sampled 11 patients with multifocal SI-NETs. The complete genome sequences of 65 tumor and tissue samples including 42 intestinal lesions, 14 adjacent lymph node metastases, 5 distant metastases, as well as of 4 normal tissue and 11 normal blood samples were determined. This allowed elucidation of phylogenetic relationships between tumors within individual patients.","abstract":"We have sampled 11 patients with multifocal SI-NETs. The complete genome sequences of 65 tumor and tissue samples including 42 intestinal lesions, 14 adjacent lymph node metastases, 5 distant metastases, as well as of 4 normal tissue and 11 normal blood samples were determined. This allowed elucidation of phylogenetic relationships between tumors within individual patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-04T18:41:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005097","title":"Oncogenic cooperation between the TCF7-SPI1 fusion and NRAS(G12D) requires β-catenin activity to drive T-cell acute lymphoblastic leukemia.","description":"In this study we investigate the role of TCF7-SPI1 fusions, more specifically in cooperation with RAS mutations. \nWe make use of patients samples. This study contains paired-end RNA sequencing of the patients, Oxford Nanopore Technologies (ONT) sequencing, single cell RNA sequencing and RNA sequencing of treatment with inhibitors of these samples.","abstract":"In this study we investigate the role of TCF7-SPI1 fusions, more specifically in cooperation with RAS mutations. \nWe make use of patients samples. This study contains paired-end RNA sequencing of the patients, Oxford Nanopore Technologies (ONT) sequencing, single cell RNA sequencing and RNA sequencing of treatment with inhibitors of these samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-05T12:26:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005098","title":"Hermansky-Pudlak syndrome type 1 causes impaired anti-microbial immunity  through a pathogenic lipid metabolism-mTOR circuit - 10x Genomics scRNAseq","description":"Mendelian diseases that present with immune-mediated disorders can provide insights into the molecular mechanisms that drive inflammation. Hermansky-Pudlak syndrome (HPS) types 1 and 4 are caused by defective vesicle trafficking involving the BLOC-3 complex. The presence of inflammatory complications such as Crohn’s disease-like inflammation and lung fibrosis in these patients remains enigmatic. Using mass cytometry we observe an augmented inflammatory monocyte compartment in HPS1 patient peripheral blood that may be associated with a TNF - and IL-1α-dominated cytokine dysregulation. HPS1 patient monocyte-derived macrophages express an inflammatory TNF-OSM mRNA gene signature and changes in lipid metabolism. Using stimulation experiments and lysosomal proteomics we show that defective lipid metabolism drives RAB32-dependent mTOR signaling, facilitated by the accumulation of mTOR on lysosomes. This pathogenic circuit translates into aberrant bacterial clearance, which can be rescued with mTORC1 inhibition. We reveal that a pathogenic lipid-mTOR signaling circuit acts as a metabolic checkpoint for defective anti-microbial activity. This mechanism may be relevant to the complex pathology of HPS1 patients featuring macrophage lipid accumulation, granuloma formation, defective anti-microbial activity and tissue inflammation. Lastly, this circuit may be present in a wider group of disorders with defective lipid metabolism and cholesterol accumulation.","abstract":"Mendelian diseases that present with immune-mediated disorders can provide insights into the molecular mechanisms that drive inflammation. Hermansky-Pudlak syndrome (HPS) types 1 and 4 are caused by defective vesicle trafficking involving the BLOC-3 complex. The presence of inflammatory complications such as Crohn’s disease-like inflammation and lung fibrosis in these patients remains enigmatic. Using mass cytometry we observe an augmented inflammatory monocyte compartment in HPS1 patient peripheral blood that may be associated with a TNF - and IL-1α-dominated cytokine dysregulation. HPS1 patient monocyte-derived macrophages express an inflammatory TNF-OSM mRNA gene signature and changes in lipid metabolism. Using stimulation experiments and lysosomal proteomics we show that defective lipid metabolism drives RAB32-dependent mTOR signaling, facilitated by the accumulation of mTOR on lysosomes. This pathogenic circuit translates into aberrant bacterial clearance, which can be rescued with mTORC1 inhibition. We reveal that a pathogenic lipid-mTOR signaling circuit acts as a metabolic checkpoint for defective anti-microbial activity. This mechanism may be relevant to the complex pathology of HPS1 patients featuring macrophage lipid accumulation, granuloma formation, defective anti-microbial activity and tissue inflammation. Lastly, this circuit may be present in a wider group of disorders with defective lipid metabolism and cholesterol accumulation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-05T16:56:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005099","title":"AncestryDNA COVID-19 GWAS with Eight Phenotypes","description":"Multiple large COVID‑19 genome-wide association studies (GWAS) have identified reproducible genetic associations indicating a genetic component to susceptibility and severity risk. Many of these previous studies ascertained COVID‑19 cases in medical clinics and hospitals, which can lead to an overrepresentation of cases with severe outcomes, such as hospitalization, intensive care unit admission, or ventilation. Here, we demonstrate the utility and validity of deep phenotyping with self-reported outcomes in a population with a large proportion of mild and subclinical cases. Using these data, we defined eight different phenotypes related to COVID‑19 outcomes: four that align with previously studied COVID‑19 definitions and four expanded definitions that focus on susceptibility given exposure, mild clinical manifestations, and an aggregate score of symptom severity. We assessed replication of 12 previously identified COVID‑19 genetic associations with all eight phenotypes in a trans-ancestry meta-analysis of European (EUR), Admixed Amerindian (LAT), Admixed African-European (AA) cohorts, and found distinct patterns of association, most notably related to the chr3/SLC6A20/LZTFL1 and chr9/ABO regions. Additionally, we performed a genome-wide analysis, which suggested certain expanded phenotypes may capture more protective associations than the established phenotypes.","abstract":"Multiple large COVID‑19 genome-wide association studies (GWAS) have identified reproducible genetic associations indicating a genetic component to susceptibility and severity risk. Many of these previous studies ascertained COVID‑19 cases in medical clinics and hospitals, which can lead to an overrepresentation of cases with severe outcomes, such as hospitalization, intensive care unit admission, or ventilation. Here, we demonstrate the utility and validity of deep phenotyping with self-reported outcomes in a population with a large proportion of mild and subclinical cases. Using these data, we defined eight different phenotypes related to COVID‑19 outcomes: four that align with previously studied COVID‑19 definitions and four expanded definitions that focus on susceptibility given exposure, mild clinical manifestations, and an aggregate score of symptom severity. We assessed replication of 12 previously identified COVID‑19 genetic associations with all eight phenotypes in a trans-ancestry meta-analysis of European (EUR), Admixed Amerindian (LAT), Admixed African-European (AA) cohorts, and found distinct patterns of association, most notably related to the chr3/SLC6A20/LZTFL1 and chr9/ABO regions. Additionally, we performed a genome-wide analysis, which suggested certain expanded phenotypes may capture more protective associations than the established phenotypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001005100","title":"Transcriptional_Consequences_of_Copy_Number_Changes_MY_HDBR_200531","description":"Every normal human cell has two copies of each non-sex chromosome. The gain or loss of an extra copy underlies many health conditions, including developmental syndromes and cancer. Ultimately, it is the patterns of genes that are turned on and off that determines which proteins a cell produces and its biological function. Despite the importance of changes in chromosome number (known as aneuploidy or copy number changes), little is known about how these changes impact patterns of gene expression. This project will aim to fill this gap by creating an atlas of patterns of gene expression in cells from developmental tissues with aberrant numbers of chromosomes. These gene expression profiles will then be compared to the patterns of expression in the same cells with two copies of each chromosome, directly measuring the precise, cell specific, consequences of copy number change on gene expression.","abstract":"Every normal human cell has two copies of each non-sex chromosome. The gain or loss of an extra copy underlies many health conditions, including developmental syndromes and cancer. Ultimately, it is the patterns of genes that are turned on and off that determines which proteins a cell produces and its biological function. Despite the importance of changes in chromosome number (known as aneuploidy or copy number changes), little is known about how these changes impact patterns of gene expression. This project will aim to fill this gap by creating an atlas of patterns of gene expression in cells from developmental tissues with aberrant numbers of chromosomes. These gene expression profiles will then be compared to the patterns of expression in the same cells with two copies of each chromosome, directly measuring the precise, cell specific, consequences of copy number change on gene expression.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-08T09:21:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005101","title":"Gut metagenomics for FINRISK 2002","description":"The main goal of the project is the study the associations between the gut metagenome and human health. The dataset contains data for n=7211 FINRISK 2002 participants who underwent fecal sampling. Demultiplexed shallow shotgun metagenomic sequences were quality filtered and adapter trimmed using Atropos (Didion et al., 2017), and human filtered using Bowtie2 (Langmead and Salzberg, 2012).","abstract":"The main goal of the project is the study the associations between the gut metagenome and human health. The dataset contains data for n=7211 FINRISK 2002 participants who underwent fecal sampling. Demultiplexed shallow shotgun metagenomic sequences were quality filtered and adapter trimmed using Atropos (Didion et al., 2017), and human filtered using Bowtie2 (Langmead and Salzberg, 2012).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005102","title":"CRISPR transduction of iPS cells","description":"Genome engineering using CRISPR/Cas9 technology enables simple, efficient and precise genomic modifications in human cells. Conventional immortalized cell lines can be easily edited or screened using genome-wide libraries with lentiviral transduction. However, cell types derived from the differentiation of induced Pluripotent Stem Cells (iPSC), which often represent more relevant, patient-derived models for human pathology, are much more difficult to engineer as CRISPR/Cas9 delivery to these differentiated cells can be inefficient and toxic. Here, we present an efficient, lentiviral transduction protocol for delivery of CRISPR/Cas9 to macrophages derived from human iPSC with efficiencies close to 100%. We demonstrate CRISPR/Cas9 knockouts for three non-essential proof-of-concept genes - HPRT1, PPIB and CDK4. We then scale the protocol and validate for a genome-wide pooled CRISPR/Cas9 loss-of-function screen. This methodology enables, for the first time, systematic exploration of macrophage involvement in immune responses, chronic inflammation, neurodegenerative diseases and cancer progression, using efficient genome editing techniques.","abstract":"Genome engineering using CRISPR/Cas9 technology enables simple, efficient and precise genomic modifications in human cells. Conventional immortalized cell lines can be easily edited or screened using genome-wide libraries with lentiviral transduction. However, cell types derived from the differentiation of induced Pluripotent Stem Cells (iPSC), which often represent more relevant, patient-derived models for human pathology, are much more difficult to engineer as CRISPR/Cas9 delivery to these differentiated cells can be inefficient and toxic. Here, we present an efficient, lentiviral transduction protocol for delivery of CRISPR/Cas9 to macrophages derived from human iPSC with efficiencies close to 100%. We demonstrate CRISPR/Cas9 knockouts for three non-essential proof-of-concept genes - HPRT1, PPIB and CDK4. We then scale the protocol and validate for a genome-wide pooled CRISPR/Cas9 loss-of-function screen. This methodology enables, for the first time, systematic exploration of macrophage involvement in immune responses, chronic inflammation, neurodegenerative diseases and cancer progression, using efficient genome editing techniques.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-08T15:12:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005103","title":"Strain for comparative analysis","description":"A pilot study examining genetic determinants of microbiome associated with long term memory acquisition of individuals from the outskirts of London.","abstract":"Background: In 2013, a prospective registry for adults with congenital heart disease (CHD) was established in Switzerland, providing detailed data on disease characteristics and outcomes: Swiss Adult Congenital HEart disease Registry (SACHER). Its aim is to improve the knowledge base of outcomes in adults with CHD. The registry design and baseline patient characteristics are reported.\nMethods: All patients with structural congenital heart defects or hereditary aortopathies, followed-up at dedicated adult CHD clinics, are asked to participate in SACHER. Data of participants are pseudonymised and collected in an electronic, web-based, database (secuTrial®). Collected data include detailed diagnosis, type of repair procedures, previous complications and adverse outcomes during follow-up.\nResults: From May 2014 to December 2016, 2836 patients (54% male, mean age 34 ± 14 years), with a wide variety of congenital heart lesions, have been enrolled into SACHER. Most prevalent were valve lesions (25%), followed by shunt lesions (22%), cyanotic and other complex congenital heart disease (16%), diseases affecting the right heart, i.e., tetralogy of Fallot or Ebstein anomaly (15%), and diseases of the left ventricular outflow tract (13%); 337 patients (12%) had concomitant congenital syndromes. The majority had undergone previous repair procedures (71%), 47% of those had one or more reinterventions.\nConclusion: SACHER collects multicentre data on adults with CHD. Its structure enables prospective data analysis to assess detailed, lesion-specific outcomes with the aim to finally improve long-term outcomes.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005104","title":"Genetic landscape of inherited retinal dystrophies affected cases in Spain","description":"Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in a Spanish cohort of patients. A retrospective hospital-based cross-sectional study was carried out on IRD affected individuals, referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to all families with available DNA using different molecular techniques. Our study provides the general landscape for IRD in Spain and our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.","abstract":"Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in a Spanish cohort of patients. A retrospective hospital-based cross-sectional study was carried out on IRD affected individuals, referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to all families with available DNA using different molecular techniques. Our study provides the general landscape for IRD in Spain and our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.","study_type":"Other","pubmed_ids":[33452396],"external_links":null,"is_released":true,"released_date":"2021-03-09T13:47:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005105","title":"Neuroinflammation_DNAseq","description":"1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"The goal of this project is to understand the causal link between cellular processes and Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. This study will use large scale mapping experiments to identify expression QTLs using variation from the HipSci resource of cell lines, and scRNAseq. We will then employ colocalization analysis (with for example AD/PD GWAS/GWAX data from OTAR037 and publically available data (Nicolas et al. 2018)) to map loci where the same causal genetic signal drives both disease risk and variation in a core microglial cell function.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005106","title":"Comparative transcriptome of CD34+ hematopoietic progenitors from myeloproliferative patients and control donors","description":"BCR-ABL-negative MPNs are related to mutations activating the JAK2/STAT pathway and occurring in hematopoietic stem cells (HSC). The most prevalent mutation is JAK2V617F. Calreticulin (CALR) and activating MPLW515 mutations are also observed in ET and PMF. Additional non-MPN mutations may be found, particularly in PMF, and can change disease phenotype or accelerate progression to myelofibrosis or leukemia.\nIn this study, we wanted to compare the transcriptome of CD34+ progenitors from JAK2V617F postive MPN patients to the CD34+ progenitors from control donors.\nThe patients were selected for their high JAK2V617F variant allele frequency (from 60 to 100% VAF). Peripheral blood from patients was collected in EDTA tubes. Hematopoietic progenitors (CD34+) were isolated from mononuclear cells (MNCs) by immunomagnetic enrichment (Miltenyi, Biotech) and were amplified for 5 days in  serum-free medium in the presence of a cocktail of human recombinant cytokines containing EPO (1 U/mL) (Amgen Thousand Oaks, CA), TPO (20 ng/mL) (Kirin, Japan), SCF (25 ng/mL) (Biovitrum AB, Sweden), IL-3 (10 ng/mL), FLT3-L (10 ng/mL), G-CSF (20 ng/mL) and IL-6 (100 U/mL) (MiltenyiBiotec).","abstract":"BCR-ABL-negative MPNs are related to mutations activating the JAK2/STAT pathway and occurring in hematopoietic stem cells (HSC). The most prevalent mutation is JAK2V617F. Calreticulin (CALR) and activating MPLW515 mutations are also observed in ET and PMF. Additional non-MPN mutations may be found, particularly in PMF, and can change disease phenotype or accelerate progression to myelofibrosis or leukemia.\nIn this study, we wanted to compare the transcriptome of CD34+ progenitors from JAK2V617F postive MPN patients to the CD34+ progenitors from control donors.\nThe patients were selected for their high JAK2V617F variant allele frequency (from 60 to 100% VAF). Peripheral blood from patients was collected in EDTA tubes. Hematopoietic progenitors (CD34+) were isolated from mononuclear cells (MNCs) by immunomagnetic enrichment (Miltenyi, Biotech) and were amplified for 5 days in  serum-free medium in the presence of a cocktail of human recombinant cytokines containing EPO (1 U/mL) (Amgen Thousand Oaks, CA), TPO (20 ng/mL) (Kirin, Japan), SCF (25 ng/mL) (Biovitrum AB, Sweden), IL-3 (10 ng/mL), FLT3-L (10 ng/mL), G-CSF (20 ng/mL) and IL-6 (100 U/mL) (MiltenyiBiotec).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-09T18:09:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005107","title":"Chronic myelomonocytic leukemia","description":"Chronic myelomonocytic leukemia is an aggressive hematological malignancy with dismal outcomes, with the pCMML subtype in particular having median OS of &lt;2 years and high rates of AML transformation (Patnaik et al., 2014). Given limited therapeutic options for affected patients, we carried out this study to define the genetic and epigenetic landscape of pCMML and identify therapies that could modify disease biology.","abstract":"Chronic myelomonocytic leukemia is an aggressive hematological malignancy with dismal outcomes, with the pCMML subtype in particular having median OS of &lt;2 years and high rates of AML transformation (Patnaik et al., 2014). Given limited therapeutic options for affected patients, we carried out this study to define the genetic and epigenetic landscape of pCMML and identify therapies that could modify disease biology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-10T09:45:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005108","title":"Integrated genomic analysis identifies driver genes and cisplatin-resistant progenitor phenotype in pediatric liver cancer","description":"Pediatric liver cancers (PLCs) comprise diverse diseases affecting infants, children and adolescents. Despite overall good prognosis, PLCs display heterogeneous response to chemotherapy. Integrated genomic analysis of 126 pediatric liver tumors showed a continuum of driver mechanisms associated with patient age, including new targetable oncogenes. In 10% of hepatoblastoma patients, all before 3 years old, we identified a mosaic premalignant clonal expansion of cells altered at the 11p15.5 locus. Analysis of spatial and longitudinal heterogeneity revealed an important plasticity between ‘Hepatocytic’, ‘Liver Progenitor’ and ‘Mesenchymal’ molecular subgroups of hepatoblastoma. We showed that during chemotherapy, ‘Liver Progenitor’ cells accumulated massive loads of cisplatin-induced mutations with a specific mutational signature, leading to the development of heavily mutated relapses and metastases. Drug screening in PLC cell lines identified promising targets for cisplatin-resistant progenitor cells, validated in mouse xenograft experiments. These data provide new insights into cisplatin resistance mechanisms in PLC and suggest alternative therapies.","abstract":"Pediatric liver cancers (PLCs) comprise diverse diseases affecting infants, children and adolescents. Despite overall good prognosis, PLCs display heterogeneous response to chemotherapy. Integrated genomic analysis of 126 pediatric liver tumors showed a continuum of driver mechanisms associated with patient age, including new targetable oncogenes. In 10% of hepatoblastoma patients, all before 3 years old, we identified a mosaic premalignant clonal expansion of cells altered at the 11p15.5 locus. Analysis of spatial and longitudinal heterogeneity revealed an important plasticity between ‘Hepatocytic’, ‘Liver Progenitor’ and ‘Mesenchymal’ molecular subgroups of hepatoblastoma. We showed that during chemotherapy, ‘Liver Progenitor’ cells accumulated massive loads of cisplatin-induced mutations with a specific mutational signature, leading to the development of heavily mutated relapses and metastases. Drug screening in PLC cell lines identified promising targets for cisplatin-resistant progenitor cells, validated in mouse xenograft experiments. These data provide new insights into cisplatin resistance mechanisms in PLC and suggest alternative therapies.","study_type":"Other","pubmed_ids":[33893148],"external_links":null,"is_released":true,"released_date":"2021-03-10T12:12:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005109","title":"Sequencing of cancer autopsies and ctDNA","description":"Tumor heterogeneity is a major obstacle for precision oncology strategies. To characterize inter-lesion heterogeneity in pre-treated cancers, we performed genetic and transcriptomic profiling of synchronous lesions from ten rapid autopsies comprising six cases of breast cancer, three of cholangiocarcinoma and one lung cancer case.  For nine patients, we studied mutation representation in circulating cell-free DNA (cfDNA).","abstract":"Tumor heterogeneity is a major obstacle for precision oncology strategies. To characterize inter-lesion heterogeneity in pre-treated cancers, we performed genetic and transcriptomic profiling of synchronous lesions from ten rapid autopsies comprising six cases of breast cancer, three of cholangiocarcinoma and one lung cancer case.  For nine patients, we studied mutation representation in circulating cell-free DNA (cfDNA).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-10T16:26:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005110","title":"International Genetics of Parkinson Disease Progression (IGPP) Consortium GWAS Summary Results","description":"To characterize how genetic variation influences the progression of Parkinson’s disease to dementia, which is a major determinant for quality of life, we performed a longitudinal genome-wide survival study (GWSS). Risk profile analysis was performed with a novel polygenic hazard score in longitudinal cohorts in the International Genetics of Parkinson Disease Progression (IGPP) Consortium.","abstract":"To characterize how genetic variation influences the progression of Parkinson’s disease to dementia, which is a major determinant for quality of life, we performed a longitudinal genome-wide survival study (GWSS). Risk profile analysis was performed with a novel polygenic hazard score in longitudinal cohorts in the International Genetics of Parkinson Disease Progression (IGPP) Consortium.","study_type":"Other","pubmed_ids":[33958783],"external_links":null,"is_released":true,"released_date":"2021-03-10T21:18:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005111","title":"IG-MYC rearrangement defines a high-risk subgroup of B-cell precursor acute lymphoblastic leukaemia","description":null,"abstract":"Translocations involving the immunoglobulin loci and the transcription factor MYC (IG-MYC) are seen in mature haematological malignancies, notably Burkitt lymphoma (BL). IG-MYC has also rarely been reported in phenotypically immature B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) where it presents a clinical management dilemma. This has historically resulted in inconsistent and suboptimal treatment, with enrolment onto clinical trials often prohibited.\nTo determine whether these patients, or what proportion of them, have BCP-ALL or BL, we conducted a detailed genetic and clinical outcome study. We observed the clonal and sub-clonal nature of this rearrangement, with copy number abnormalities of chromosome 1 (28/90, 31%) and rearrangements of BCL2/BCL6 (BCL2/6-r) (15/90, 16.6%) being the most frequent co-existent chromosomal abnormalities. Genomic sequencing identified precursor-like V(D)J region breakpoints and frequent mutations in genes implicated in BCP-ALL (KRAS, ASMTL and IKZF1). The methylome and transcriptome of patients determined two main features: (1) samples clustered according to established ALL cytogenetic features (KMT2A-r or IGH-DUX4); (2) samples with IG-MYC-r as the main cytogenetic finding formed a distinct cluster, separate from BL. The exception was cases with BCL2/6-r, which we propose represent a different disease, more akin to adult “double-hit” lymphomas.\nWhen treated on historic ALL protocols, children with IG-MYC-r BCP-ALL had a 3 year EFS and OS rates of 47% and 60%, representing a high-risk disease. The underlying molecular features seen in most patients with IG-MYC rearrangements are strongly indicative of ALL suggesting there is no rationale to exclude them from standard or novel ALL therapies. Prospective enrolment onto risk-stratified clinical trials is critical to define and improve outcome in this high-risk group of BCP-ALL.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-11T08:45:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005112","title":"The INFORM Precision Medicine Study for High-Risk Pediatric Malignancies","description":null,"abstract":"The INFORM precision medicine study is an international program for pediatric patients with high-risk relapsed tumors (and some very high-risk primary diagnoses), to offer the potential for identifying personalized treatment targets after other therapeutic options have been exhausted. Matched tumor and blood samples are subjected to comprehensive molecular profiling with whole exome, low-coverage whole genome and RNA sequencing within a clinically-relevant timeframe. Since its initiation in 2013, over 1,000 patients have been recruited onto the study, with many patients having received targeted therapies based on the identified molecular alterations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-11T10:37:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005113","title":"MPN_phylogenies_in_JAK_CALR_negative_patients_to_understand_their_clonal_basis","description":"MPN phylogenies in JAK/CALR negative patients to understand their clonal basis.","abstract":"MPN phylogenies in JAK/CALR negative patients to understand their clonal basis.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-11T16:34:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005114","title":"Example!_Strain for comparative analysis","description":"A pilot study examining genetic determinants associated with long term memory acquisition using exome sequencing of individuals from the outskirts of London.","abstract":"Example!_Background: In 2013, a prospective registry for adults with congenital heart disease (CHD) was established in Switzerland, providing detailed data on disease characteristics and outcomes: Swiss Adult Congenital HEart disease Registry (SACHER). Its aim is to improve the knowledge base of outcomes in adults with CHD. The registry design and baseline patient characteristics are reported.\n\nMethods: All patients with structural congenital heart defects or hereditary aortopathies, followed-up at dedicated adult CHD clinics, are asked to participate in SACHER. Data of participants are pseudonymised and collected in an electronic, web-based, database (secuTrial®). Collected data include detailed diagnosis, type of repair procedures, previous complications and adverse outcomes during follow-up.\n\nResults: From May 2014 to December 2016, 2836 patients (54% male, mean age 34 ± 14 years), with a wide variety of congenital heart lesions, have been enrolled into SACHER. Most prevalent were valve lesions (25%), followed by shunt lesions (22%), cyanotic and other complex congenital heart disease (16%), diseases affecting the right heart, i.e., tetralogy of Fallot or Ebstein anomaly (15%), and diseases of the left ventricular outflow tract (13%); 337 patients (12%) had concomitant congenital syndromes. The majority had undergone previous repair procedures (71%), 47% of those had one or more reinterventions.\n\nConclusion: SACHER collects multicentre data on adults with CHD. Its structure enables prospective data analysis to assess detailed, lesion-specific outcomes with the aim to finally improve long-term outcomes.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005115","title":"Cryopreservation of human cancers conserves tumour heterogeneity for single-cell multi-omics analysis","description":null,"abstract":"Background: High throughput single-cell RNA sequencing (scRNA-Seq) has emerged as a powerful tool for exploring cellular heterogeneity amongst complex human cancers. scRNA-Seq studies using fresh human surgical tissue is logistically difficult, precludes histopathological triage of samples and limits the ability to perform batch processing. This hinderance can often introduce technical biases when integrating patient datasets and increase experimental costs. Although tissue preservation methods have been previously explored to address such issues, it is yet to be examined on complex human tissues, such as solid cancers, and on high throughput scRNA-Seq platforms. \nResults: We show that the viable cryopreservation of human cancers provides high quality single-cell transcriptomes using the Chromium 10X platform. We sequenced a total of ~120,000 cells from fresh and cryopreserved replicates across three breast cancers, two prostate cancers and a cutaneous melanoma. Importantly, tumour heterogeneity identified from fresh tissues was largely conserved in cryopreserved replicates. We show that sequencing of single cells prepared from cryopreserved tissue fragments or from cryopreserved cell suspensions is comparable to sequenced cells prepared from fresh tissue, with cryopreserved cell suspensions displaying higher correlations with fresh tissue in gene expression. We showed that cryopreservation had minimal impacts on results of downstream analyses such as biological pathway enrichment. For some tumours, cryopreservation modestly increased cell stress signatures compared to freshly analysed tissue. Further, we demonstrate the advantage of cryopreserving whole-cells for immunophenotyping methods such as CITE-Seq, which is impossible using other preservation methods such as single nuclei-sequencing.\nConclusions: Our study guides new experimental designs for tissue biobanking for future clinical single-cell RNA sequencing studies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-12T02:18:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005116","title":"WES of clonally related neuroblastoma and teratoma","description":"Mature teratomas are usually benign tumors that rarely undergo malignant transformation. We report an advanced neuroblastoma arising in a mature teratoma of the ovary. Whole-exome sequencing identified extensive copy-neutral LOH in both neuroblastoma and teratoma elements, suggesting that the neuroblastoma evolved from the teratoma.","abstract":"Mature teratomas are usually benign tumors that rarely undergo malignant transformation. We report an advanced neuroblastoma arising in a mature teratoma of the ovary. Whole-exome sequencing identified extensive copy-neutral LOH in both neuroblastoma and teratoma elements, suggesting that the neuroblastoma evolved from the teratoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-13T20:11:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005117","title":"Whole-exome sequencing performed on a patient with chronic myelomonocytic leukemia and B cell acute lymphoblastic leukemia","description":"We studied the rare case of a patient who underwent transformation of myelodysplastic syndrome to chronic myelomonocytic leukemia and B cell acute lymphoblastic leukemia. We used fluorescence-activated cell sorting and whole-exome sequencing to identify driver mutations in the various clones. This allowed us to propose a model of branching clonal evolution with a possible germline predisposition to cancer.","abstract":"We studied the rare case of a patient who underwent transformation of myelodysplastic syndrome to chronic myelomonocytic leukemia and B cell acute lymphoblastic leukemia. We used fluorescence-activated cell sorting and whole-exome sequencing to identify driver mutations in the various clones. This allowed us to propose a model of branching clonal evolution with a possible germline predisposition to cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-14T20:33:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005118","title":"Identification of novel colorectal cancer predisposition genes","description":null,"abstract":"There is clear evidence that clinical genetic counseling for hereditary cancer saves lives and relieves anxiety. Our aim is to identify novel genes that predispose to familial colorectal cancer. We follow the empirical gene discovery paradigm by identifying high-risk families diagnosed with the same cancer in several family members. Such families and samples are identified from the world’s largest biobank of 16,000 familial cancers in Szczecin. For this study we identified 15 colorectal cancer families with several affected family members. Germline DNA from cases and unaffected family members are sequenced genome-wide at the DKFZ core facility, one of Europe’s top sequencing centers. Based on the proof-of-principle study on melanoma, a single family may allow identification of a high-risk variant when the new genome-wide sequencing technology is applied. In that example, the detected variant targeted a transcription factor binding site which turned out to be the most common gene variant in melanoma yet described, with implications to prognosis. The present project aims at cancer prevention in identifying novel high-risk variants for which predictive gene testing can be established.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-15T09:19:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005119","title":"CRISPR_repair_outcomes","description":"The goal of this project is to perform a systematic analysis of the repair outcomes in CRISPR targeted human iPS cells. In order to profile the integration outcomes, we will use the CRISPR/Cas9-mediated, amplification-free target enrichment method for long-read sequencing from Oxford Nanopore.","abstract":"The goal of this project is to perform a systematic analysis of the CRISPR repair outcomes in targeted human iPS cells. In order to profile the integration outcomes, we will use the CRISPR/Cas9-mediated, amplification-free target enrichment method for long-read sequencing from Oxford Nanopore.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005120","title":"Avadomide induces degradation of ZMYM2 fusion oncoproteins in hematologic malignancies","description":null,"abstract":"We have extended the potential clinical scope of thalidomide analogs by the identification of a novel avadomide-dependent CRL4-CRBN substrate, ZMYM2. Our study showed that avadomide induces ubiquitination and degradation of ZMYM2-FGFR1 and ZMYM2-FLT3, two chimeric oncoproteins involved in hematologic malignancies, providing a proof-of-concept for drug-induced degradation of transcription factor fusion proteins by thalidomide analogs.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005121","title":"ATAC-seq of uncultured CD112high and CD112low long-term(LT) human hematopoietic stem cells (HSC)  from umbilical cord blood","description":"ATAC-sequencing was performed to establish chromatin accessibility signatures  that underlie the differential in vitro priming and regeneration phenotypes of CD112high and CD112low LT-HSC. CD112high and CD112low LT-HSC from 2-3 independent human umbilical cord blood pools were prospectively isolated for DNA extraction, library preparation and sequencing.","abstract":"ATAC-sequencing was performed to establish chromatin accessibility signatures  that underlie the differential in vitro priming and regeneration phenotypes of CD112high and CD112low LT-HSC. CD112high and CD112low LT-HSC from 2-3 independent human umbilical cord blood pools were prospectively isolated for DNA extraction, library preparation and sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-15T18:59:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005122","title":"Whole exome sequencing of a patient with Amyotrophic Lateral Sclerosis","description":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is hallmarked by upper and lower motor neuron neurodegeneration. Here, we present a patient with a Cytoplasmic dynein 1 heavy chain 1 (DYNC1H1) mutation who fulfilled the ALS El Escorial criteria, and we review relevant literature. Using whole-exome sequencing, we identified a non-synonymous point mutation in DYNC1H1 [c.4106A&gt;G (p. Q1369R))] as a likely major contributor to the ALS phenotype. In silico structural analysis, molecular dynamics simulation, and protein stability analysis predicted that this variant may increase DYNC1H1 protein stability. Also, this variant may disrupt binding of the transcription factor TFAP4 potentially acting as duon. Since a) DYNC1H1 forms part of a ubiquitous eukaryotic motor protein complex and b) disruption of dynein function by perturbation of the dynein-dynactin protein complex is implicated in other motor neuron degeneration categories, this variant could disrupt processes like retrograde axonal transport, neuronal migration, and protein recycling. Our findings expand the heterogenous spectrum of DYNC1H1 mutations−associated phenotype and advocate screening for DYNC1H1 in ALS-related gene panels to aid in ALS molecular diagnostics.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005123","title":"Metastatic porocarcinoma: genomic profiling and functional validation identify novel therapeutic opportunities (Hipo H021)","description":null,"abstract":"Eccrine porocarcinoma (EPC) is a rare skin cancer arising from the eccrine sweat glands. Metastasis is associated with a high mortality rate. There is no effective standard therapy, implying an urgent need for novel treatment strategies. Using comprehensive genomic and transcriptomic profiling, we detected widespread alterations that affect cancer-relevant cellular processes like cell cycle regulation and proliferation pathways including p53, p16INK4a, EGFR und PAK signaling in patient-derived tissue of metastatic EPC, suggesting treatment with targeted and immune therapy. Alterations in these pathways could be validated by immunohistochemical analyses of 2 different EPC cohorts and in functional studies of a patient-derived EPC cell line. With EGFR-directed therapy and immune checkpoint inhibition a metastatic EPC patient survived for more than 2 years. These observations highlight the potential of genomics-guided precision medicine studies in identifying novel treatment strategies for rare cancers like EPC and possibly other adnexal carcinoma family members.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005124","title":"Example!_Strain for comparative analysis","description":"Example!_A pilot study examining genetic determinants of microbiome associated with long term memory acquisition of individuals from the outskirts of London.","abstract":"Example!_Background: In 2013, a prospective registry for adults with congenital heart disease (CHD) was established in Switzerland, providing detailed data on disease characteristics and outcomes: Swiss Adult Congenital HEart disease Registry (SACHER). Its aim is to improve the knowledge base of outcomes in adults with CHD. The registry design and baseline patient characteristics are reported.\nMethods: All patients with structural congenital heart defects or hereditary aortopathies, followed-up at dedicated adult CHD clinics, are asked to participate in SACHER. Data of participants are pseudonymised and collected in an electronic, web-based, database (secuTrial®). Collected data include detailed diagnosis, type of repair procedures, previous complications and adverse outcomes during follow-up.\nResults: From May 2014 to December 2016, 2836 patients (54% male, mean age 34 ± 14 years), with a wide variety of congenital heart lesions, have been enrolled into SACHER. Most prevalent were valve lesions (25%), followed by shunt lesions (22%), cyanotic and other complex congenital heart disease (16%), diseases affecting the right heart, i.e., tetralogy of Fallot or Ebstein anomaly (15%), and diseases of the left ventricular outflow tract (13%); 337 patients (12%) had concomitant congenital syndromes. The majority had undergone previous repair procedures (71%), 47% of those had one or more reinterventions.\nConclusion: SACHER collects multicentre data on adults with CHD. Its structure enables prospective data analysis to assess detailed, lesion-specific outcomes with the aim to finally improve long-term outcomes.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005125","title":"Copy number analysis by SNP array","description":"Hybridization-based genomic profiling arrays were performed using Genome-Wide Human SNP Array 6.0 or the CytoScan HD array, according to the manufacturer’s instructions (Affymetrix, Santa Clara, CA, USA) now part of Thermo Fisher Scientific (Thermo Fisher Scientific, Inc.) Following the procedures of sample preparation, hybridization, and scanning, the CEL file of Genome-Wide\nHuman SNP Array 6.0 was analyzed as previously described (Magrangeas et al. 2012) and the CEL file of CytoScan HD array was analyzed using the Chromosome Analysis Suite (ChAS) software (Thermo Fisher Scientific, Inc).","abstract":"Hybridization-based genomic profiling arrays were performed using Genome-Wide Human SNP Array 6.0 or the CytoScan HD array, according to the manufacturer’s instructions (Affymetrix, Santa Clara, CA, USA) now part of Thermo Fisher Scientific (Thermo Fisher Scientific, Inc.) Following the procedures of sample preparation, hybridization, and scanning, the CEL file of Genome-Wide\nHuman SNP Array 6.0 was analyzed as previously described (Magrangeas et al. 2012) and the CEL file of CytoScan HD array was analyzed using the Chromosome Analysis Suite (ChAS) software (Thermo Fisher Scientific, Inc).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-16T11:02:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005126","title":"scRNA_seq_Analysis_of_iPSC_derived_cortical_neurons","description":"This study is part of a larger Open Targets project that aims to understand the cellular basis of neurodevelopmental and psychiatric disorders, and identify novel therapeutic targets for them. This study involves characterisation of iPSC-derived cortical neurons from wild-type and mutant cell lines using scRNA-seq.","abstract":"This study is part of a larger Open Targets project that aims to understand the cellular basis of neurodevelopmental and psychiatric disorders, and identify novel therapeutic targets for them. This study involves characterisation of iPSC-derived cortical neurons from wild-type and mutant cell lines using scRNA-seq. We will differentiate ~30 human iPSC lines towards a cortical fate using a pooled approach and profile the cells at multiple timepoints over their development. Transcriptomic profiles from different developmental stages will be compared between wild-type and mutant (patient-derived, engineered gene knock-outs) cells.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005127","title":"Accurate detection and classification of pediatric sarcomas based on cell-free DNA fragmentation patterns","description":"Sequencing of cell-free DNA in the blood of cancer patients (“liquid biopsy”) provides attractive opportunities not only for early diagnosis, but also for minimally invasive monitoring of treatment response and disease courses. To unlock liquid biopsy analysis for pediatric tumors with few genetic aberrations, we developed an integrated genetic/epigenetic analysis method and applied it to 241 deep whole-genome sequencing profiles of 95 patients with Ewing sarcoma and 31 patients with other pediatric sarcomas. We achieved sensitive detection and classification of circulating tumor DNA in peripheral blood independent of any genetic alterations. We evaluated different metrics for cell-free DNA fragmentation analysis and developed LIQUORICE, a bioinformatic tool for detecting circulating tumor DNA based on tumor-specific chromatin structure. Using machine learning methods, we combined several fragmentation-based metrics into an integrated approach for liquid biopsy analysis tailored to cancers with low mutation rates but widespread epigenetic deregulation. Clinical associations highlighted the potential value of cfDNA fragmentation patterns as prognostic biomarkers in Ewing sarcoma. \nAdditionally, we performed low coverage whole-genome-sequencing on 43 tumor biopsy samples from patients with Ewing sarcoma, in order to compare copy number aberrations detected in cell-free DNA and biopsy samples of the same patients. For validation of the epigenetic signatures inferred from cell-free DNA, we further performed reduced representation bisulfite sequencing (RRBS) on 38 matched biopsy samples from patients with Ewing sarcoma. \nIn summary, our study provides a comprehensive analysis of circulating tumor DNA beyond recurrent somatic mutations, and it renders the benefits of liquid biopsy more readily accessible for childhood cancers.","abstract":"Sequencing of cell-free DNA in the blood of cancer patients (“liquid biopsy”) provides attractive opportunities not only for early diagnosis, but also for minimally invasive monitoring of treatment response and disease courses. To unlock liquid biopsy analysis for pediatric tumors with few genetic aberrations, we developed an integrated genetic/epigenetic analysis method and applied it to 241 deep whole-genome sequencing profiles of 95 patients with Ewing sarcoma and 31 patients with other pediatric sarcomas. We achieved sensitive detection and classification of circulating tumor DNA in peripheral blood independent of any genetic alterations. We evaluated different metrics for cell-free DNA fragmentation analysis and developed LIQUORICE, a bioinformatic tool for detecting circulating tumor DNA based on tumor-specific chromatin structure. Using machine learning methods, we combined several fragmentation-based metrics into an integrated approach for liquid biopsy analysis tailored to cancers with low mutation rates but widespread epigenetic deregulation. Clinical associations highlighted the potential value of cfDNA fragmentation patterns as prognostic biomarkers in Ewing sarcoma. \nAdditionally, we performed low coverage whole-genome-sequencing on 43 tumor biopsy samples from patients with Ewing sarcoma, in order to compare copy number aberrations detected in cell-free DNA and biopsy samples of the same patients. For validation of the epigenetic signatures inferred from cell-free DNA, we further performed reduced representation bisulfite sequencing (RRBS) on 38 matched biopsy samples from patients with Ewing sarcoma. \nIn summary, our study provides a comprehensive analysis of circulating tumor DNA beyond recurrent somatic mutations, and it renders the benefits of liquid biopsy more readily accessible for childhood cancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-17T07:56:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005128","title":"Multiregional sequencing of IDH-WT glioblastoma reveals high genetic heterogeneity and a dynamic evolutionary history","description":"Glioblastoma is the most common and aggressive primary brain malignancy in adults. In addi-tion to extensive inter-patient heterogeneity, glioblastoma shows intra-tumor extensive cellular and molecular heterogeneity, both spatially and temporally. This heterogeneity is one of the main reasons for the poor prognosis and overall survival. Moreover, it raises the important question of whether the molecular characterization of a single bioptic sample, as performed in standard di-agnostics, actually represents the entire lesion. In this study, we sequenced the whole-exome of nine spatially different cancer regions of three primary glioblastomas. We characterized their mutational profiles and copy number alterations, with implications for our understanding of tu-mor biology in relation to clonal architecture and evolutionary dynamics, as well as therapeuti-cally relevant alterations.","abstract":"Glioblastoma is the most common and aggressive primary brain malignancy in adults. In addi-tion to extensive inter-patient heterogeneity, glioblastoma shows intra-tumor extensive cellular and molecular heterogeneity, both spatially and temporally. This heterogeneity is one of the main reasons for the poor prognosis and overall survival. Moreover, it raises the important question of whether the molecular characterization of a single bioptic sample, as performed in standard di-agnostics, actually represents the entire lesion. In this study, we sequenced the whole-exome of nine spatially different cancer regions of three primary glioblastomas. We characterized their mutational profiles and copy number alterations, with implications for our understanding of tu-mor biology in relation to clonal architecture and evolutionary dynamics, as well as therapeuti-cally relevant alterations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-17T09:59:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005129","title":"Whole genome sequencing study of paediatric leukemia","description":null,"abstract":"Whole genome sequencing of pediatric leukemias","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005130","title":"RNA-Seq of vocal fold fibroblasts in Reinke’s edema and control subjects","description":"The voice disorder Reinke’s edema (RE) is a smoking- and voice-abuse associated benign lesion of the vocal folds, defined by an edema of the Reinke space, accompanied with pathological microvasculature changes and immune cell infiltration. Vocal fold fibroblasts (VFF) are the main cell type of the lamina propria and play a key role in the disease progression. Current therapy is restricted to symptomatic treatment. Hence, there is an urgent need for a better understanding of the molecular causes of the disease. In the present study, we investigated differential expression profiles of RE and control VFF by means of RNA sequencing. In addition, fast gene set enrichment analysis (FGSEA) was performed in order to obtain involved biological processes, mRNA and protein levels of targets of interest were further evaluated. We identified 74 differentially regulated genes in total, 19 of which were upregulated and 55 downregulated. Differential expression analysis and FGSEA revealed upregulated genes and pathways involved in extracellular matrix (ECM) remodeling, inflammation and fibrosis. Downregulated genes and pathways were involved in ECM degradation, cell cycle control and proliferation. The current study addressed for the first time a direct comparison of VFF from RE to control and evaluated immediate functional consequences.","abstract":"The voice disorder Reinke’s edema (RE) is a smoking- and voice-abuse associated benign lesion of the vocal folds, defined by an edema of the Reinke space, accompanied with pathological microvasculature changes and immune cell infiltration. Vocal fold fibroblasts (VFF) are the main cell type of the lamina propria and play a key role in the disease progression. Current therapy is restricted to symptomatic treatment. Hence, there is an urgent need for a better understanding of the molecular causes of the disease. In the present study, we investigated differential expression profiles of RE and control VFF by means of RNA sequencing. In addition, fast gene set enrichment analysis (FGSEA) was performed in order to obtain involved biological processes, mRNA and protein levels of targets of interest were further evaluated. We identified 74 differentially regulated genes in total, 19 of which were upregulated and 55 downregulated. Differential expression analysis and FGSEA revealed upregulated genes and pathways involved in extracellular matrix (ECM) remodeling, inflammation and fibrosis. Downregulated genes and pathways were involved in ECM degradation, cell cycle control and proliferation. The current study addressed for the first time a direct comparison of VFF from RE to control and evaluated immediate functional consequences.","study_type":"Other","pubmed_ids":[34206882],"external_links":null,"is_released":true,"released_date":"2021-03-17T13:50:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005132","title":"Epigenomic profiling and transcriptomic profiling of LUAD patients tumor tissues and tumor adjacent tissues","description":"To provide an in-depth understanding of the epigenomic heterogeneity of LUAD, we here investigated the H3K27ac histone modification profiles of tumors and adjacent normal lung tissues from 42 LUAD patients and explored the role of epigenetic alterations in LUAD progression. We also  investigated transcriptomic alterations among 36 patients tumor tissues.","abstract":"To provide an in-depth understanding of the epigenomic heterogeneity of LUAD, we here investigated the H3K27ac histone modification profiles of tumors and adjacent normal lung tissues from 42 LUAD patients and explored the role of epigenetic alterations in LUAD progression. We also  investigated transcriptomic alterations among 36 patients tumor tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-18T04:09:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005133","title":"Test","description":null,"abstract":"Test submssion","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005134","title":"Engineering large chromosomal deletions by CRISPR-Cas9","description":"Arm-level chromosomal deletions are a prevalent and defining feature of cancer. A high degree of tumor-type and subtype specific recurrencies suggest a selective oncogenic advantage. However, due to their large size it has been difficult to pinpoint the oncogenic drivers that confer this advantage. Suitable functional genomics approaches to study the oncogenic driving capacity of arm-level deletions are limited. Here we present an effective technique to engineer arm-level deletions by CRISPR-Cas9 and create isogenic cell line models. We simultaneously induce double-strand breaks (DSBs) at two ends of a chromosomal arm and select the cells that have lost the intermittent region. Using this technique, we induced arm-level deletions on chromosome 11q (65 MB) and chromosome 6q (53 MB) in neuroblastoma cell lines.  Such isogenic models enable further research on the role of arm-level deletions in tumor development and growth, and their possible therapeutic potential.","abstract":"Arm-level chromosomal deletions are a prevalent and defining feature of cancer. A high degree of tumor-type and subtype specific recurrencies suggest a selective oncogenic advantage. However, due to their large size it has been difficult to pinpoint the oncogenic drivers that confer this advantage. Suitable functional genomics approaches to study the oncogenic driving capacity of arm-level deletions are limited. Here we present an effective technique to engineer arm-level deletions by CRISPR-Cas9 and create isogenic cell line models. We simultaneously induce double-strand breaks (DSBs) at two ends of a chromosomal arm and select the cells that have lost the intermittent region. Using this technique, we induced arm-level deletions on chromosome 11q (65 MB) and chromosome 6q (53 MB) in neuroblastoma cell lines.  Such isogenic models enable further research on the role of arm-level deletions in tumor development and growth, and their possible therapeutic potential.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-19T09:02:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005135","title":"Clonal_dynamics_and_mutation_burden_in_male_germline___DupSeq","description":"This work aim to study clonal dynamics of pathogenic mutations in male germline. Using Nanoseq method, sperm from normal panel will be compared with sperm from men who have either clinical phynotypes or they have child(ren) with germline predisposition syndromes.","abstract":"nherited cancers play a major role in about 5 to 10 percent of all cancers. It is increasingly apparent that many inherited cancer syndromes arise through new mutations acquired most likely in germline of fathers. Most of the burden of high-penetrance germline predisposition to cancer arises through mutations acquired during spermatogenesis. However, little is known about mutagenesis within the hierarchy of spermatogenesis or factors that influence rates of mutation in the testes. It is likely that mutations in spermatogonia stem cells that confer weaker selective advantage and generate smaller clonal expansions in the testes, become enrich in sperms and transmit to the next generations. However, due to the low sensitivity of standard genomic approaches, subclonal mutations that may only be present in small contiguous areas within testes have been poorly investigated.  \n\nThis proposal aims to measure the mutational burden of pathogenic variants in sperms and to identify the processes that underlie their acquisition.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-19T13:04:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005136","title":"Are CTCs or ctDNA suitable to determine oncogenic mutations in HCC patients","description":null,"abstract":"Circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) may be used for\ndiagnostic or prognostic purposes in patients with hepatocellular carcinoma (HCC). We aim to determine whether CTCs or ctDNA are suitable to determine oncogenic\nmutations in HCC patients.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005137","title":"Characterization of human iPSC-derived dopaminergic neurons with 16p11.2 CNVs","description":null,"abstract":"We studied human induced pluripotent stem cells (iPSCs)-derived dopaminergic (DA) neuron populations carrying CNVs of 16p11.2 duplication and 16p11.2 deletion.\nPreviously, healthy human iPSCs were edited using CRISPR-Cas9 method to produce isogenic lines with 16p11.2 deletion or 16p11.2 duplication. We differentiated these\nisogenic iPSC lines into neural precursor cells and dopaminergic neurons and collected RNA samples for gene expression analyses with RNA sequencing. Our aim was to\nidentify differences in the expression of synaptic markers, neuronal differentiation markers, and neuron specific receptors that affect functionality of the neurons with 16p11.2\nCNVs compared to isogenic control lines. We also studied physiological properties of these isogenic iPSC-derived DA neurons with 16p11.2 CNVs. In addition, we studied\nexpression and activation of a specific molecular pathway KCTD13-RHOA in the iPSC derived DA neuron populations with 16p11.2 CNVs.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-22T09:36:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005138","title":"Increased trunk fat is associated with altered gene expression in breast tissue of normal weight women","description":null,"abstract":"Even though an individual has normal weight that doesn't necessary mean that individual is healthy. There are some normal weight individuals who are metabolically unhealthy due to excess trunk fat. Using RNA-seq data, we observed gene expression changes in breast tissue of normal weight women with trunk fat.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-22T13:45:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005139","title":"Epigenomic profile of diverse cancer","description":"The samples are from patients of multiple cancer types. The library preparation protocol was developed by the laboratory. The DNA libraries were then sequenced with 150bp paired-end reads.","abstract":"The samples are from patients of multiple cancer types. The library preparation protocol was developed by the laboratory. The DNA libraries were then sequenced with 150bp paired-end reads.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005140","title":"Mixed Histology Lung Cancers Driven by Transcriptomic Features rather than Genomic Characteristics","description":null,"abstract":"Histology plays an essential role in therapeutic decision-making for lung cancer patients. However, the molecular determinants of lung cancer histology are largely unknown. We conducted whole-exome sequencing (WES) and microarray profiling on 19 micro-dissected tumor regions of different histologic subtypes from 9 patients with lung cancers of mixed histology.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-22T21:54:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005141","title":"Chemotherapy accelerates genomic aging of normal blood in children treated for cancer","description":"Whole genome sequencing (WGS) data obtained from clonally expanded hematopoietic stem and progenitor cells (HSPCs) from pediatric cancer patients before and after therapy exposure. In addition, WGS data of cord-blood derived HSPCs clones exposed to various chemotherapeutics and radiation was obtained.","abstract":"Whole genome sequencing (WGS) data obtained from clonally expanded hematopoietic stem and progenitor cells (HSPCs) from pediatric cancer patients before and after therapy exposure. In addition, WGS data of cord-blood derived HSPCs clones exposed to various chemotherapeutics and radiation was obtained.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-23T06:58:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005142","title":"-","description":"-","abstract":"-","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-12-02T12:27:25.447723+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005143","title":"Neuroinflammation_DNAseq","description":"The goal of this project is to understand the causal link between cellular processes and Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. This study will use large scale mapping experiments to identify expression QTLs using variation from the HipSci resource of cell lines, and scRNAseq. We will then employ colocalization analysis (with for example AD/PD GWAS/GWAX data from OTAR037 and publically available data (Nicolas et al. 2018)) to map loci where the same causal genetic signal drives both disease risk and variation in a core microglial cell function.1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"The goal of this project is to understand the causal link between cellular processes and Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. This study will use large scale mapping experiments to identify expression QTLs using variation from the HipSci resource of cell lines, and scRNAseq. We will then employ colocalization analysis (with for example AD/PD GWAS/GWAX data from OTAR037 and publically available data (Nicolas et al. 2018)) to map loci where the same causal genetic signal drives both disease risk and variation in a core microglial cell function.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005144","title":"Single cell RNA sequencing of synovial B cells in early Rheumatoid Arthritis","description":"Rheumatoid Arthritis (RA) is a prevalent autoimmune disease characterized by inflammation of the peripheral joints and occurence of autoantibodies, i.e. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA), in circulation. Previous studies have shown that there are memory B cells and autoantibody producing plasma cells present in the joint tissue of patients with long-standing RA. However, it has remained unclear, whether these B cell populations are already present in the joint tissue of patients at the disease onset and whether these are autoreactive. Here, we used a single cell RNA sequencing approach to dissect the B cell repertoire at this early timepoint. We found evidence for B and T cell interaction and presence of memory and plasma cell pools in ACPA- and ACPA+ RA. Our results demonstrated clonal relationships between the memory and plasma cell compartments and autoreactivity within the plasma cell pool. These findings challenge our understanding of the local adaptive immune response in the joints of ACPA- and ACPA+ RA patients with direct implications for B and T cell targeting therapy in both patient subgroups.","abstract":"Rheumatoid Arthritis (RA) is a prevalent autoimmune disease characterized by inflammation of the peripheral joints and occurence of autoantibodies, i.e. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA), in circulation. Previous studies have shown that there are memory B cells and autoantibody producing plasma cells present in the joint tissue of patients with long-standing RA. However, it has remained unclear, whether these B cell populations are already present in the joint tissue of patients at the disease onset and whether these are autoreactive. Here, we used a single cell RNA sequencing approach to dissect the B cell repertoire at this early timepoint. We found evidence for B and T cell interaction and presence of memory and plasma cell pools in ACPA- and ACPA+ RA. Our results demonstrated clonal relationships between the memory and plasma cell compartments and autoreactivity within the plasma cell pool. These findings challenge our understanding of the local adaptive immune response in the joints of ACPA- and ACPA+ RA patients with direct implications for B and T cell targeting therapy in both patient subgroups.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-24T11:18:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005145","title":"H021-Master Umbrella study2 (not to be released)","description":null,"abstract":"hipo_021 data pool for several publications. WES, WGS and RNA samples of different cancers. Only for internal DKFZ use, not to be released. Part2","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-24T15:35:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005146","title":"Somatic_mutations_in_normal_proximal_airway_epithelium_after_immunotherapy","description":"In this study, single cells have been isolated from normal and pre-invasive lung cancer lesions before/after immunotherapy (PD-1 blocking antibody) from one patient. These have been grown into colonies that will then be whole genome sequenced.","abstract":"Previously, we studied the landscape of somatic mutations in normal bronchial epithelium, which revealed that tobacco smoking increases the variance of mutation burden both within and between patients. Immunotherapy has been shown to improve survival in advanced non-small cell lung cancers, especially those with high mutation burden. However, our understanding of how immuntherapy changes the clonal architecture in normal proximal airway epithelium is limited. In this study, single cells have been isolated from normal and pre-invasive lung cancer lesions before/after immunotherapy (PD-1 blocking antibody) from one patient. These have been grown into colonies that will then be whole genome sequenced.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005147","title":"Assessment of the Toll-like receptor 3 response in hepatocytes","description":"Toll like receptor 3 (TLR3) is an endosomal pattern recognition receptor (PRR), recognizing double stranded RNA (dsRNA) as a distinct Pathogen-associated molecular pattern (PAMP) for viral infections. We aim to understand the contribution of TLR3 to the dsRNA response in hepatocytes. The innate immune response of cells of hepatic origin (Huh7, Huh7.5, PH5CH and primary human hepatocytes (PHH)) was analyzed by transcriptome analysis (RNAseq) upon supernatant delivery or transfection of synthetic dsRNA (poly(I:C)). Expression of TLR3 and RIG-I was reconstituted by lentiviral transduction in Huh7 and Huh7.5 cells. Huh7 and Huh7.5 cells, devoid of functional TLR3 expression, did not respond to supernatant delivery of poly(I:C), in contrast to PH5CH and PHH, confirming a high selectivity of this method towards activating TLR3 in all hepatocyte models.","abstract":"Toll like receptor 3 (TLR3) is an endosomal pattern recognition receptor (PRR), recognizing double stranded RNA (dsRNA) as a distinct Pathogen-associated molecular pattern (PAMP) for viral infections. We aim to understand the contribution of TLR3 to the dsRNA response in hepatocytes. The innate immune response of cells of hepatic origin (Huh7, Huh7.5, PH5CH and primary human hepatocytes (PHH)) was analyzed by transcriptome analysis (RNAseq) upon supernatant delivery or transfection of synthetic dsRNA (poly(I:C)). Expression of TLR3 and RIG-I was reconstituted by lentiviral transduction in Huh7 and Huh7.5 cells. Huh7 and Huh7.5 cells, devoid of functional TLR3 expression, did not respond to supernatant delivery of poly(I:C), in contrast to PH5CH and PHH, confirming a high selectivity of this method towards activating TLR3 in all hepatocyte models.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-25T10:29:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005148","title":"this is a test 2021","description":null,"abstract":"testestestest","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005149","title":"Accurate_assessement_of_mutation_burden_in_blood_duplex","description":"Bot seq allows accurate quantification of mutation burden without requiring a clonal (eg colony/LCM biopsy) sample. This allows expansion of mutation burden studies to larger cohorts to understand modifiers (eg environmental/germline). However, most larger cohorts have blood collected, not grans. We want to understand if we can use mutation burden reliably from whole blood or whether the variable amount of lymphocytes will render the data useless. So, these are 7 individuals with matched gran, WBC and MNCs collected (by the M, G and W in the middle of the specimen label in column G). The idea is to see how much the burden varies across these sample type within individuals.","abstract":"Bot seq allows accurate quantification of mutation burden without requiring a clonal (eg colony/LCM biopsy) sample. This allows expansion of mutation burden studies to larger cohorts to understand modifiers (eg environmental/germline). However, most larger cohorts have blood collected, not grans. We want to understand if we can use mutation burden reliably from whole blood or whether the variable amount of lymphocytes will render the data useless. So, these are 7 individuals with matched gran, WBC and MNCs collected (by the M, G and W in the middle of the specimen label in column G). The idea is to see how much the burden varies across these sample type within individuals.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005150","title":"ICI-pneumonitis immune landscape uncovered by scRNA-seq","description":null,"abstract":"Rationale: Immune checkpoint inhibitor-related pneumonitis is the most fatal immune-related adverse event associated with PD-1/PD-L1 blockade. A broad differential diagnosis and lack of targeted treatments hampers timely and efficacious management.\nObjectives: We aim to gain novel insights into the pathophysiology of immune checkpoint inhibitor-related pneumonitis, thereby identifying putative diagnostic biomarkers and therapeutic targets.\nMethods: Single-cell RNA and T-cell receptor sequencing was performed on bronchoalveolar lavage fluid of immune checkpoint inhibitor-related pneumonitis, and compared to infectious pneumonia samples (both COVID-19 and non-COVID-19). Intercellular communication and differential gene expression analyses allowed us to identify discriminating immune features between these three disease entities.\nMeasurements and Main Results T-helper 17 cells were markedly enriched in the bronchoalveolar lavage fluid of patients experiencing immune checkpoint inhibitor-related pneumonitis, compared to infectious pneumonia cases. Additionally, intercellular communication and subsequent differential gene expression analyses revealed a qualitative predominance of T-helper 17 over regulatory T-cells in immune checkpoint inhibitor-related pneumonitis. The former exhibited a pathogenic phenotype, co-expressing IL23R, TBX21 and IFNG with reduced IL10 expression, while the latter showed decreased immunoregulatory function.  Myeloid cell populations did not display disease-specific shifts.\nConclusions: Our results indicate that immune checkpoint inhibitor-related pneumonitis is driven by a dominant T-helper 17 immune response, which is insufficiently countered by regulatory T-cells. T-helper 17 cells, or their cytokine products, should be validated as diagnostic biomarkers. Targeting the IL-23/T-helper 17 axis merits further research as an effective, well-tolerated and safe treatment for immune checkpoint inhibitor-related pneumonitis.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005151","title":"Single-cell transcriptome of human fetal pancreas and in vitro pancreatic spheroids","description":"This dataset combines single cell transcriptome data from fetal pancreas at 7-10 wpc, embryonic stem cell-derived pancreas progenitors and spheroids generated from both fetal pancreas and human pluripotent stem cell-derived pancreas progenitors.","abstract":"This dataset combines single cell transcriptome data from fetal pancreas at 7-10 wpc, embryonic stem cell-derived pancreas progenitors and spheroids generated from both fetal pancreas and human pluripotent stem cell-derived pancreas progenitors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-25T15:24:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005152","title":"Bulk ATAC-Seq (Replicate 3) on sorted cord blood hematopoietic populations","description":null,"abstract":"A third replicate of Bulk ATAC-Seq was performed on human cord-blood derived hematopoietis popuations using the following markers:\n\nLT-HSC; CD34+CD38-CD45RA-CD90+CD49f+\nST-HSC; CD34+CD38-CD45RA-CD90-CD49f-\nMLP; CD34+CD38-CD45RA+\nCMP; CD34+CD38+ CD10-CD45RA-Flt3+CD71-\nGMP; CD34+CD38+ CD10-CD45RA+ CD71-\nMEP; CD34+CD38+ CD10-CD45RA-Flt3-CD71+\nT cell; CD3+CD19-\nB cell; CD19+CD3-\nNK cell; CD56+CD3-CD19-CD14-\nGranulocyte; CD14+CD15+CD3-CD19-\nMonocyte; CD14+CD15-CD3-CD19-\nDC; CD11c+CD45+\nErythroid cell; CD71+GPA+\n\nThis replicate follows the same protocol but was produced following the analyses in Takayama et al, 2020 (cell stem cell), it will be used in subsequent publications but is not part of that initial paper.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005153","title":"Nanoseq_of_the_Degenerative_Joint_Disease__WGS_","description":"Study somatic mutation in joint tissues, including mutation burden accumulation through lifespan and mutational signatures.","abstract":"Study somatic mutation in joint tissues, including mutation burden accumulation through lifespan and mutational signatures.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005154","title":"Nanoseq_of_the_Ageing_Brain__WGS_","description":"Study somatic mutation in ageing brain tissues, including mutation burden accumulation through lifespan and mutational signatures.","abstract":"Study somatic mutation in ageing brain tissues, including mutation burden accumulation through lifespan and mutational signatures.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-25T15:53:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005155","title":"Functional_changes_associated_with_drivers_in_chronic_liver_disease__WGS_","description":"Despite decades of research and many insightful findings, a complete understanding of the pathogenesis of chronic liver disease continues to elude us. Recently, recurrent mutations in genes involved in lipid metabolism and insulin pathway have been identified in the liver of patients with non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ARLD). While preliminary data suggests that these mutations are pathogenic and may be contributing to disease phenotype, the functional consequences of these abberrations are not fully understood.  This study will aim to characterize the downstream effects of somatic mutations recurrent in liver tissue of patients with chronic liver disease. The data in this study will be generated by whole-genome sequencing of laser dissected microbiopsies from liver samples of patients with chronic liver diseases of various aetiologies. The whole genome data will be then matched to transcriptomic and lipidomic data from adjacent tissue sections to infer genotype-phenotype associations.","abstract":"This study will exlpore downstream effects of somatic mutations recurrent in liver tissue of patients with chronic liver disease. The data in this study will be generated by whole-genome sequencing of laser dissected microbiopsies from liver samples of patients with chronic liver diseases of various aetiologies. The whole genome data will be then matched to transcriptomic data from z-stacked tissue sections to infer genotype-phenotype associations.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005156","title":"Functional_changes_associated_with_drivers_in_chronic_liver_disease__exome_","description":"Despite decades of research and many insightful findings, a complete understanding of the pathogenesis of chronic liver disease continues to elude us. Recently, recurrent mutations in genes involved in lipid metabolism and insulin pathway have been identified in the liver of patients with non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ARLD). While preliminary data suggests that these mutations are pathogenic and may be contributing to disease phenotype, the functional consequences of these abberrations are not fully understood.  This study will aim to characterize the downstream effects of somatic mutations recurrent in liver tissue of patients with chronic liver disease. The data in this study will be generated by whole-exome sequencing of laser dissected microbiopsies from liver samples of patients with chronic liver diseases of various aetiologies. The exome sequencing data will be then matched to transcriptomic and lipidomic data from adjacent tissue sections to infer genotype-phenotype associations.","abstract":"This study will explore downstream effects of somatic mutations recurrent in liver tissue of patients with chronic liver disease. The data in this study will be generated by whole-exome sequencing of laser dissected microbiopsies from liver samples of patients with chronic liver diseases of various aetiologies. The whole exome sequencing data will be then matched to transcriptomic data from z-stacked tissue sections to infer genotype-phenotype associations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005157","title":"Mutational_landscape_in_haemochromatosis__WGS_","description":"Somatic mutation has recently been shown to play a role in disease other than cancer. Driver mutations associated with lipid metabolism and insulin pathway have been identified in non-alcoholic fatty liver disease (NAFLD). It is plausible that driver mutations seen in NAFLD are a consequence of selection pressure exerted on hepatocytes in the context of excess fat accumulation. It has not been investigated whether selection pressure and driver landscape varies between chronic liver diseases of different aetiologies. This study aims to investigate mutational landscape in haemochromatosis, which is a disorder caused by a build-up of iron in the liver. We aim to use data generated by whole-genome sequencing of laser-dissected microbiopsies from diseased livers to characterize driver landscape and mutational signatures in haemochromatosis patients.","abstract":"Somatic mutation has recently been shown to play a role in disease other than cancer. Driver mutations associated with lipid metabolism and insulin pathway have been identified in non-alcoholic fatty liver disease (NAFLD). It is plausible that driver mutations seen in NAFLD are a consequence of selection pressure exerted on hepatocytes in the context of excess fat accumulation. It has not been investigated whether selection pressure and driver landscape varies between chronic liver diseases of different aetiologies. This study aims to investigate mutational landscape in haemochromatosis, which is a disorder caused by a build-up of iron in the liver. We aim to use data generated by whole-genome sequencing of laser-dissected microbiopsies from diseased livers to characterize driver landscape and mutational signatures in haemochromatosis patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-25T16:53:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005158","title":"Mutational_landscape_in_haemochromatosis__exome_","description":"Somatic mutation has recently been shown to play a role in disease other than cancer. Driver mutations associated with lipid metabolism and insulin pathway have been identified in non-alcoholic fatty liver disease (NAFLD). It is plausible that driver mutations seen in NAFLD are a consequence of selection pressure exerted on hepatocytes in the context of excess fat accumulation. It has not been investigated whether selection pressure and driver landscape varies between chronic liver diseases of different aetiologies. This study aims to investigate mutational landscape in haemochromatosis, which is a disorder caused by a build-up of iron in the liver. We aim to use data generated by whole-exome sequencing of laser-dissected microbiopsies from diseased livers to characterize driver landscape and mutational signatures in haemochromatosis patients.","abstract":"Somatic mutation has recently been shown to play a role in disease other than cancer. Driver mutations associated with lipid metabolism and insulin pathway have been identified in non-alcoholic fatty liver disease (NAFLD). It is plausible that driver mutations seen in NAFLD are a consequence of selection pressure exerted on hepatocytes in the context of excess fat accumulation. It has not been investigated whether selection pressure and driver landscape varies between chronic liver diseases of different aetiologies. This study aims to investigate mutational landscape in haemochromatosis, which is a disorder caused by a build-up of iron in the liver. We aim to use data generated by whole-exome sequencing of laser-dissected microbiopsies from diseased livers to characterize driver landscape and mutational signatures in haemochromatosis patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-25T16:55:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005159","title":"WGS bam","description":"We established 21 patient-derived pHGG orthotopic xenograft (PDOX) models and eight matched cell lines from diverse groups of pHGG. Here are all available Whole Genome Sequencing (WGS) data from patient tumor, PDOX, and cell lines from our study.","abstract":"We established 21 patient-derived pHGG orthotopic xenograft (PDOX) models and eight matched cell lines from diverse groups of pHGG. Here are all available Whole Genome Sequencing (WGS) data from patient tumor, PDOX, and cell lines from our study.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-28T17:20:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005160","title":"WES bam","description":"We established 21 patient-derived pHGG orthotopic xenograft (PDOX) models and eight matched cell lines from diverse groups of pHGG. Here are all available Whole Exome Sequencing (WES) data from patient tumor, PDOX, and cell lines from our study.","abstract":"We established 21 patient-derived pHGG orthotopic xenograft (PDOX) models and eight matched cell lines from diverse groups of pHGG. Here are all available Whole Exome Sequencing (WES) data from patient tumor, PDOX, and cell lines from our study.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-28T17:39:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005161","title":"RNA-seq bam","description":"We established 21 patient-derived pHGG orthotopic xenograft (PDOX) models and eight matched cell lines from diverse groups of pHGG. Here are all available RNA Sequencing (RNA-seq) data from patient tumor, PDOX, and cell lines from our study.","abstract":"We established 21 patient-derived pHGG orthotopic xenograft (PDOX) models and eight matched cell lines from diverse groups of pHGG. Here are all available RNA Sequencing (RNA-seq) data from patient tumor, PDOX, and cell lines from our study.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-28T17:45:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005162","title":"RODAM_Inflammation and CVD risk","description":null,"abstract":"We performed an epigenome wide association study to identify loci associated with serum C-reactive protein (marker of inflammation) among Ghanaians and further assessed whether the identified differentially methylated positions (DMPs) were associated with 10-year predicted CVD risk.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005163","title":"Human Papilloma Virus Integration Strictly Correlates with Global Genome Instability in Head and Neck Cancer","description":null,"abstract":"We applied a combination of whole genome sequencing and optical genome mapping to interrogate the genome structure of HPV-positive oropharyngeal squamous cell carcinomas. We found the virus integrated in the host genome in two thirds of the tumors examined but resided solely extrachromosomally in the other third. Integration of the virus occurred at essentially random sites within the genome and at more than one site in the genome in half the cases of integration.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005171","title":"Genotype data from 'Evidence of the interplay of genetics and culture in Ethiopia'","description":null,"abstract":"The rich linguistic, ethnic and cultural diversity of Ethiopia provides an unprecedented opportunity to understand the level to which cultural factors correlate with -- and shape -- genetic structure in human populations. Using primarily new genetic variation data covering 1,214 Ethiopians representing 68 different ethnic groups, together with information on individuals’ birthplaces, linguistic/religious practices and 31 cultural practices, we disentangle the effects of geographic distance, elevation, and social factors on the genetic structure of Ethiopians today. We provide evidence of associations between social behaviours and genetic differences among present-day peoples. We show that genetic similarity is broadly associated with linguistic affiliation, but also identify pronounced genetic similarity among groups from disparate language classifications that may in part be attributable to recent intermixing. We also illustrate how groups reporting the same culture traits are more genetically similar on average and show evidence of recent intermixing, suggesting that shared cultural traits may promote admixture. In addition to providing insights into the genetic structure and history of Ethiopia, these results identify the most important cultural and geographic proxies for genetic differentiation and provide a resource for designing sampling protocols for future genetic studies involving Ethiopians.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-30T15:54:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005172","title":"Somatic_mutation_in_benign_prostatic_hyperplasia","description":"In this study we aim to characterise the landscape of somatic mutation and clonal selection in human benign prostatic hyperplasia. The study combines whole-exome sequencing and whole-genome sequencing of microbiopsies from prostate samples. The range of patients studied will include patients diagnosed with benign prostatic hyperplasia.","abstract":"In this study we aim to characterise the landscape of somatic mutation and clonal selection in human benign prostatic hyperplasia. The study combines whole-exome sequencing and whole-genome sequencing of microbiopsies from prostate samples. The range of patients studied will include patients diagnosed with benign prostatic hyperplasia.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005173","title":"An integrated multi-omic cellular atlas of human breast cancers","description":null,"abstract":"Breast cancers are complex cellular ecosystems where heterotypic interactions play central roles in disease progression and response to therapy. However, our knowledge of their cellular composition and organization remains limited. We present a single cell and spatially resolved transcriptomics analysis of human breast cancers. We develop a single cell method of intrinsic subtype classification (scSubtype) to reveal recurrent neoplastic cell heterogeneity. Immunophenotyping using CITE-Seq provides high-resolution immune profiles, including novel macrophage populations with high expression of PD-L1 and PD-L2 immune checkpoint ligands and associations with clinical outcome. We show that mesenchymal cells generate diverse functions and cell surface protein expression through differentiation within 3 major lineages. Stromal-immune niches were spatially organized in tumors, offering insights into anti-tumor immune regulation. Using single cell signatures, we deconvoluted large breast cancer cohorts to stratify them into nine clusters, termed ‘ecotypes’, with unique cellular compositions and clinical outcomes. This study provides a comprehensive transcriptional atlas of the cellular architecture of breast cancer.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-03-31T05:33:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005174","title":"sn-RNAseq profiling of the impact of a cytokine storm model in human cardiac organoids","description":"We developed conditions to model conditions of diastolic dysfunction caused by inflammatory factors in human cardiac organoids. Our organoid model is based on conditions promoting maturation (Mills et al., PNAS, 2017 and Voges et al., In Revision) and incorporating human pluripotent stem cell derived cardiomyocytes, epicardial cells, fibroblasts, endothelial cells and pericytes. Following 15 days of differentiation (Voges et al., Development, 2017) we formed human cardiac organoids incorporating both our multicellular differentiation (Mills et al., PNAS, 2017) and additional endothelial cells (Voges et al., In Revision). After another 12 days of maturation in 5 days maturation medium and 5 days weaning medium (Voges et al., In Revision) human cardiac organoids were either treated with weaning medium or “cardiac cytokine storm” comprised of  100 ng/ml IFNg, 10 ng/ml IL-1 β and 10 µg/ml poly(I:C). After 48 hours human cardiac organoids were harvested and snap frozen in -80C before nuclei isolation and single nuclei RNA sequencing.Pooled hCO (~40) were homogenized in 4 mL lysis buffer (300 mM sucrose, 10 mM Tris-HCl (pH = 8), 5 mM CaCl2, 5 mM magnesium acetate, 2 mM EDTA, 0.5 mM EGTA, 1 mM DTT)(all Sigma-Aldrich) with 30 strokes of a dounce tissue grinder (Wheaton). Large pieces of hCO were allowed to settle and homogenate was passed through pre-wetted 40 µm cell strainers (Becton Dickinson). Remaining hCO material in the douncer was resuspended in 4 mL and the douncing and filtering steps were repeated twice. All steps of the homogenization were performed on ice. The filtered homogenate was centrifuged at 1500 x g for 5 min at 4oC. Nuclei pellets were then re-suspended in PBS. A fraction of resuspended nuclei were then stained with hoechst nuclear stain (1:500 dilution) and counted on a haemocytometer under fluorescent microscope.The nuclei were then re-centrifuged (1500 x g for 5 min at 4°C) and resuspended at a density to load ~5,000 nuclei per sample. Cell were loaded into the Chromium Controller (10X Genomics) for gel bead emulsion (GEM) formation. Library preparation was conducted according to the manufacturer’s recommended protocol using the Chromium Next GEM Single Cell 3’ GEM, Library &amp; Gel Bead Kit v3.1. Libraries were sequenced on the NextSeq 500/550 v2 (Illumina) with 150 bp reads.In the snRNA-seq we note the lower than expected percentage of non-myocytes and the loss of endothelial cells (Mills et al., PNAS, 2017 and Voges et al., In Revision), indicating the protocol requires further optimization for hCO samples.","abstract":"We developed conditions to model conditions of diastolic dysfunction caused by inflammatory factors in human cardiac organoids. Our organoid model is based on conditions promoting maturation (Mills et al., PNAS, 2017 and Voges et al., In Revision) and incorporating human pluripotent stem cell derived cardiomyocytes, epicardial cells, fibroblasts, endothelial cells and pericytes. Following 15 days of differentiation (Voges et al., Development, 2017) we formed human cardiac organoids incorporating both our multicellular differentiation (Mills et al., PNAS, 2017) and additional endothelial cells (Voges et al., In Revision). After another 12 days of maturation in 5 days maturation medium and 5 days weaning medium (Voges et al., In Revision) human cardiac organoids were either treated with weaning medium or “cardiac cytokine storm” comprised of  100 ng/ml IFNg, 10 ng/ml IL-1 β and 10 µg/ml poly(I:C). After 48 hours human cardiac organoids were harvested and snap frozen in -80C before nuclei isolation and single nuclei RNA sequencing.Pooled hCO (~40) were homogenized in 4 mL lysis buffer (300 mM sucrose, 10 mM Tris-HCl (pH = 8), 5 mM CaCl2, 5 mM magnesium acetate, 2 mM EDTA, 0.5 mM EGTA, 1 mM DTT)(all Sigma-Aldrich) with 30 strokes of a dounce tissue grinder (Wheaton). Large pieces of hCO were allowed to settle and homogenate was passed through pre-wetted 40 µm cell strainers (Becton Dickinson). Remaining hCO material in the douncer was resuspended in 4 mL and the douncing and filtering steps were repeated twice. All steps of the homogenization were performed on ice. The filtered homogenate was centrifuged at 1500 x g for 5 min at 4oC. Nuclei pellets were then re-suspended in PBS. A fraction of resuspended nuclei were then stained with hoechst nuclear stain (1:500 dilution) and counted on a haemocytometer under fluorescent microscope.The nuclei were then re-centrifuged (1500 x g for 5 min at 4°C) and resuspended at a density to load ~5,000 nuclei per sample. Cell were loaded into the Chromium Controller (10X Genomics) for gel bead emulsion (GEM) formation. Library preparation was conducted according to the manufacturer’s recommended protocol using the Chromium Next GEM Single Cell 3’ GEM, Library &amp; Gel Bead Kit v3.1. Libraries were sequenced on the NextSeq 500/550 v2 (Illumina) with 150 bp reads.In the snRNA-seq we note the lower than expected percentage of non-myocytes and the loss of endothelial cells (Mills et al., PNAS, 2017 and Voges et al., In Revision), indicating the protocol requires further optimization for hCO samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-01T04:51:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005178","title":"Single-cell analysis of retinoblastoma heterogeneity","description":null,"abstract":"We studied a primary retinoblastoma sample with single-cell RNA-seq (10X genomics Chromium V2).","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-01T12:42:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005179","title":"Direct RNA sequencing of human hippocampal tissues","description":null,"abstract":"Pending","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005180","title":"Degradation of Janus kinases in CRLF2-rearranged acute lymphoblastic leukemia","description":"We evaluated the efficacy of proteolysis-targeting chimeras (PROTACs) directed against Janus kinases. Solving the structure of FDA-approved type I JAK inhibitors ruxolitinib and baricitinib bound to the JAK2 JH1 tyrosine kinase domain enabled the rational design and optimization of Cereblon (CRBN)-directed JAK PROTACs utilizing multiple derivatives of JAK inhibitors, linkers and CRBN-specific molecular glues. The resulting JAK PROTACs were evaluated for target degradation by proteomic approaches, and activity tested in CRLF2-rearranged cell line and xenograft models of ALL.","abstract":"We evaluated the efficacy of proteolysis-targeting chimeras (PROTACs) directed against Janus kinases. Solving the structure of FDA-approved type I JAK inhibitors ruxolitinib and baricitinib bound to the JAK2 JH1 tyrosine kinase domain enabled the rational design and optimization of Cereblon (CRBN)-directed JAK PROTACs utilizing multiple derivatives of JAK inhibitors, linkers and CRBN-specific molecular glues. The resulting JAK PROTACs were evaluated for target degradation by proteomic approaches, and activity tested in CRLF2-rearranged cell line and xenograft models of ALL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-02T01:48:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005181","title":"G3BP2-KIT drives leukemia amenable to kinase inhibition in Ph-like ALL","description":"We describe a patient with Ph-like ALL, in which leukemic cells harbored an in-frame fusion between the GTPase-activating protein (SH3 domain)-binding protein 2 (G3BP2) and the KIT proto-oncogene.","abstract":"We describe a patient with Ph-like ALL, in which leukemic cells harbored an in-frame fusion between the GTPase-activating protein (SH3 domain)-binding protein 2 (G3BP2) and the KIT proto-oncogene.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-02T18:03:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005182","title":"Pediatric Papillary Thyroid Carcinoma RNA-Seq","description":"Papillary thyroid carcinoma (PTC) is the most common malignancy amongst adolescent and young adult women. Clinical and genomic features of PTC in children differ from those in adults. Historically, a substantial proportion (~50%) of pediatric PTC (PPTC) lack any of the common driver mutations typical of adult PTC. Thus, molecular diagnostics developed for adults may not be valid in children. We applied novel bioinformatic pipelines to RNASeq analysis of pediatric thyroid tumors to identify known and novel fusion oncogenes as drivers of tumorigenesis and to define gene expression patterns among tumors. Analysis of 38 samples resulted in identification of 16 previously reported oncogenic fusions and three novel candidate fusions. In conducting these analyses, we reduced the proportion of cancers with unknown drivers from approximately 50% to 6%. Gene expression analysis identified three distinct categories of tumors. These studies represent the first unbiased genomic approach to childhood PTC. Novel bioinformatic pipeline.  \nGEC Identified 3 distinct classes. DICER1, PTEN segregated with benign tumors. \n&gt;90% of PPTC carry identifiable ongognic driver variants, however, the landscape differs from that in adults and existing tools for tumor genotyping in adults may not be applicable to pediatric tumors.  \nBACKGROUND: Papillary thyroid carcinoma demonstrates clinically distinct behaviour in pediatric patients when compared to adults, with increased regional and distal metastases, more frequent recurrence, yet overall highly favourable prognosis. Recent tumor genotyping has demonstrated that in pediatric tumors, ***-*** do not carry the most common genomic variants found in adult PTC, leaving a substantial proportion of driver-unknown or “dark matter” tumors.  \nMETHODS: We established a cohort of 52 pediatric PTC and performed quantitative-PCR genotyping followed in a subset by whole exome and whole transcriptome (RNASeq) sequencing using a novel, robust bioinformatic pipeline to identify oncogenic fusion transcripts. Gene expression analysis was used to derive distinct clusters. \nRESULTS: In 52 pediatric PTC, genotyping identified BRAFV600E(21%), NRASQ61R(2%), RET/PTC1 (21%), RET/PTC3 (17%) or PAX8-PPAR in 33 (63%) of tumors. Among the remaining 19 tumors, oncogenic variants were identified in /19 (%). The variants included SNVs in DICER1, ETV6-NTRK3, PTEN and 9 additional oncogenic fusions including two previously-undescribed fusion transcripts, *** and ***.  \nCONCLUSIONS: The genomic landscape of PTC differs between children and adults. In children, there is a substantial fraction of tumors that are unexplained by variants typical of adult PTC. This discrepancy is explained largely by uncommon oncogenic fusions which can be identified by whole-transcriptome analysis.","abstract":"Papillary thyroid carcinoma (PTC) is the most common malignancy amongst adolescent and young adult women. Clinical and genomic features of PTC in children differ from those in adults. Historically, a substantial proportion (~50%) of pediatric PTC (PPTC) lack any of the common driver mutations typical of adult PTC. Thus, molecular diagnostics developed for adults may not be valid in children. We applied novel bioinformatic pipelines to RNASeq analysis of pediatric thyroid tumors to identify known and novel fusion oncogenes as drivers of tumorigenesis and to define gene expression patterns among tumors. Analysis of 38 samples resulted in identification of 16 previously reported oncogenic fusions and three novel candidate fusions. In conducting these analyses, we reduced the proportion of cancers with unknown drivers from approximately 50% to 6%. Gene expression analysis identified three distinct categories of tumors. These studies represent the first unbiased genomic approach to childhood PTC. Novel bioinformatic pipeline.  \nGEC Identified 3 distinct classes. DICER1, PTEN segregated with benign tumors. \n&gt;90% of PPTC carry identifiable ongognic driver variants, however, the landscape differs from that in adults and existing tools for tumor genotyping in adults may not be applicable to pediatric tumors.  \nBACKGROUND: Papillary thyroid carcinoma demonstrates clinically distinct behaviour in pediatric patients when compared to adults, with increased regional and distal metastases, more frequent recurrence, yet overall highly favourable prognosis. Recent tumor genotyping has demonstrated that in pediatric tumors, ***-*** do not carry the most common genomic variants found in adult PTC, leaving a substantial proportion of driver-unknown or “dark matter” tumors.  \nMETHODS: We established a cohort of 52 pediatric PTC and performed quantitative-PCR genotyping followed in a subset by whole exome and whole transcriptome (RNASeq) sequencing using a novel, robust bioinformatic pipeline to identify oncogenic fusion transcripts. Gene expression analysis was used to derive distinct clusters. \nRESULTS: In 52 pediatric PTC, genotyping identified BRAFV600E(21%), NRASQ61R(2%), RET/PTC1 (21%), RET/PTC3 (17%) or PAX8-PPAR in 33 (63%) of tumors. Among the remaining 19 tumors, oncogenic variants were identified in /19 (%). The variants included SNVs in DICER1, ETV6-NTRK3, PTEN and 9 additional oncogenic fusions including two previously-undescribed fusion transcripts, *** and ***.  \nCONCLUSIONS: The genomic landscape of PTC differs between children and adults. In children, there is a substantial fraction of tumors that are unexplained by variants typical of adult PTC. This discrepancy is explained largely by uncommon oncogenic fusions which can be identified by whole-transcriptome analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-06T01:14:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005183","title":"Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts - CRC - EurOPDX - IRCC_UNITO","description":null,"abstract":"Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical\nstudies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution\nduring PDX engraftment and propagation, impacting the accuracy of PDX modeling of human\ncancer. Here we exhaustively analyze copy number alterations (CNAs) in 1451 PDX and matched\npatient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing\nand microarray data displayed substantially higher resolution and dynamic range than gene\nexpression-based inferences, and they also showed strong CNA conservation from PTs through\nlate-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-\nlate trios confirmed high-resolution CNA retention. We observed no significant enrichment of\ncancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between\npatient and PDX tumors were comparable to variations in multi-region samples within patients.\nOur study demonstrates the lack of systematic copy number evolution driven by the PDX mouse\nhost.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005184","title":"Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts-BRCA-EurOPDX-VHIO","description":null,"abstract":"Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical\nstudies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution\nduring PDX engraftment and propagation, impacting the accuracy of PDX modeling of human\ncancer. Here we exhaustively analyze copy number alterations (CNAs) in 1451 PDX and matched\npatient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing\nand microarray data displayed substantially higher resolution and dynamic range than gene\nexpression-based inferences, and they also showed strong CNA conservation from PTs through\nlate-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-\nlate trios confirmed high-resolution CNA retention. We observed no significant enrichment of\ncancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between\npatient and PDX tumors were comparable to variations in multi-region samples within patients.\nOur study demonstrates the lack of systematic copy number evolution driven by the PDX mouse\nhost.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005185","title":"Clonal_dynamics_and_mutation_burden_in_male_germline___WGS","description":"This work aim to study clonal dynamics of pathogenic mutations in male germline. Using Nanoseq method, sperm from normal panel will be compared with sperm from men who have either clinical phynotypes or they have child(ren) with germline predisposition syndromes.","abstract":"Inherited cancers play a major role in about 5 to 10 percent of all cancers. It is increasingly apparent that many inherited cancer syndromes arise through new mutations acquired most likely in germline of fathers. Most of the burden of high-penetrance germline predisposition to cancer arises through mutations acquired during spermatogenesis. However, little is known about mutagenesis within the hierarchy of spermatogenesis or factors that influence rates of mutation in the testes. It is likely that mutations in spermatogonia stem cells that confer weaker selective advantage and generate smaller clonal expansions in the testes, become enrich in sperms and transmit to the next generations. However, due to the low sensitivity of standard genomic approaches, subclonal mutations that may only be present in small contiguous areas within testes have been poorly investigated.  \n\nThis proposal aims to measure the mutational burden of pathogenic variants in sperms and to identify the processes that underlie their acquisition.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005186","title":"Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-institutional Prospective Study","description":null,"abstract":"The prevalence and features of treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC) are not well characterized in the era of modern androgen receptor (AR)-targeting therapy. We sought to characterize the clinical and genomic features of t-SCNC in a multi-institutional prospective study.  Patients with progressive, metastatic castration-resistant prostate cancer (mCRPC) underwent metastatic tumor biopsy and were followed for survival. Metastatic biopsy specimens underwent independent, blinded pathology review along with RNA/DNA sequencing.  A total of 202 consecutive patients were enrolled. One hundred forty-eight (73%) had prior disease progression on abiraterone and/or enzalutamide. The biopsy evaluable rate was 79%. The overall incidence of t-SCNC detection was 17%. AR amplification and protein expression were present in 67% and 75%, respectively, of t-SCNC biopsy specimens. t-SCNC was detected at similar proportions in bone, node, and visceral organ biopsy specimens. Genomic alterations in the DNA repair pathway were nearly mutually exclusive with t-SCNC differentiation ( P = .035). Detection of t-SCNC was associated with shortened overall survival among patients with prior AR-targeting therapy for mCRPC (hazard ratio, 2.02; 95% CI, 1.07 to 3.82). Unsupervised hierarchical clustering of the transcriptome identified a small-cell-like cluster that further enriched for adverse survival outcomes (hazard ratio, 3.00; 95% CI, 1.25 to 7.19). A t-SCNC transcriptional signature was developed and validated in multiple external data sets with &gt; 90% accuracy. Multiple transcriptional regulators of t-SCNC were identified, including the pancreatic neuroendocrine marker PDX1.  t-SCNC is present in nearly one fifth of patients with mCRPC and is associated with shortened survival. The near-mutual exclusivity with DNA repair alterations suggests t-SCNC may be a distinct subset of mCRPC. Transcriptional profiling facilitates the identification of t-SCNC and novel therapeutic targets.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005187","title":"Pediatric Papillary Thyroid Carcinoma Whole Exome Sequencing","description":"BACKGROUND: Pediatric papillary thyroid carcinoma (PPTC) is distinct from adult-onset disease. Despite higher rates of regional and distal metastases and more frequent recurrence, there is, paradoxically, a highly favourable prognosis. Historically, only 40-50% of childhood PTC are driven by genomic variants common to adult PTC, while the oncogenic drivers in the remainder are unknown.  \nMETHODS: Fifty-two PPTCs were genotyped by candidate gene testing, followed, in a subset (n=32), by whole exome (WES) and transcriptome sequencing (RNASeq) to identify oncogenic variants in driver-unknown tumors and to explore gene expression patterns. \nFINDINGS: Thirty-one tumors (60%) carried variants identified by candidate gene testing, specifically: BRAFV600E(22%), NRASQ61R(2%), RET-CCDC6(19%), RET-NCOA4(15%) and PAX8-PPARG. Among the 21 remaining tumors with negative first-line genotyping, oncogenic variants were identified in 19 (90%). These were enriched with oncogenic fusions, with 11 non-recurrent fusion transcripts identified, including two that had not been previously described: STRN-RET and TG-PBF. Most fusions were associated with 3’ receptor tyrosine kinase (RTK) moieties: RET, MET, ALK and NTRK3. Gene expression analysis defined three distinct clusters, which demonstrated differing expression of genes involved in thyroid differentiation and MAPK signaling.  \nINTERPRETATION: Exome and transcriptome-wide sequencing identify genomic drivers of PPTC in 98% of tumors, whereas conventional genotyping leaves many tumors genetically unexplained. PPTC is driven, in the majority of cases, by oncogenic fusion transcripts involving one of a limited number of RTKs. These observations have broad implications for diagnostic testing and for therapeutic options in children with advanced disease.","abstract":"BACKGROUND: Pediatric papillary thyroid carcinoma (PPTC) is distinct from adult-onset disease. Despite higher rates of regional and distal metastases and more frequent recurrence, there is, paradoxically, a highly favourable prognosis. Historically, only 40-50% of childhood PTC are driven by genomic variants common to adult PTC, while the oncogenic drivers in the remainder are unknown.  \nMETHODS: Fifty-two PPTCs were genotyped by candidate gene testing, followed, in a subset (n=32), by whole exome (WES) and transcriptome sequencing (RNASeq) to identify oncogenic variants in driver-unknown tumors and to explore gene expression patterns. \nFINDINGS: Thirty-one tumors (60%) carried variants identified by candidate gene testing, specifically: BRAFV600E(22%), NRASQ61R(2%), RET-CCDC6(19%), RET-NCOA4(15%) and PAX8-PPARG. Among the 21 remaining tumors with negative first-line genotyping, oncogenic variants were identified in 19 (90%). These were enriched with oncogenic fusions, with 11 non-recurrent fusion transcripts identified, including two that had not been previously described: STRN-RET and TG-PBF. Most fusions were associated with 3’ receptor tyrosine kinase (RTK) moieties: RET, MET, ALK and NTRK3. Gene expression analysis defined three distinct clusters, which demonstrated differing expression of genes involved in thyroid differentiation and MAPK signaling.  \nINTERPRETATION: Exome and transcriptome-wide sequencing identify genomic drivers of PPTC in 98% of tumors, whereas conventional genotyping leaves many tumors genetically unexplained. PPTC is driven, in the majority of cases, by oncogenic fusion transcripts involving one of a limited number of RTKs. These observations have broad implications for diagnostic testing and for therapeutic options in children with advanced disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-07T00:45:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005188","title":"Platelet response in aspirin adherent pregnant women","description":"We conducted an unbiased genome-wide assessment of genomic factors that may influence response to low-dose aspirin in pregnant women at high risk of pre-eclampsia in two pregnancy cohorts: Liverpool (n=91) and Dublin (n=91). We applied UK Axiom microarray technology for GWAS investigations. We specified tight phenotyping with COX-selective urinary 11-dehydrothromboxane B2 (pg/mg creatinine) and accounted for adherence/platelet exposure to aspirin by detection of aspirin’s principal urinary metabolite, SUA, with nuclear magnetic resonance (NMR).","abstract":"We conducted an unbiased genome-wide assessment of genomic factors that may influence response to low-dose aspirin in pregnant women at high risk of pre-eclampsia in two pregnancy cohorts: Liverpool (n=91) and Dublin (n=91). We applied UK Axiom microarray technology for GWAS investigations. We specified tight phenotyping with COX-selective urinary 11-dehydrothromboxane B2 (pg/mg creatinine) and accounted for adherence/platelet exposure to aspirin by detection of aspirin’s principal urinary metabolite, SUA, with nuclear magnetic resonance (NMR).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-07T15:31:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005189","title":"Nasal DNA methylation at three CpG sites predicts childhood allergic disease","description":null,"abstract":"We used machine learning models to systematically integrate large-scale multi-omics data from genomics, DNA methylation in blood, and nasal and environmental factors. We firstly evaluated the prediction power of each omics layer and identified that the prediction power was largely attributed to nasal methylation. We further built a prediction model based on only three nasal CpG sites that can predict childhood allergic disease.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-07T15:56:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005190","title":"HCA_Embryo_Foetal_WSSS_Dev_RNA","description":"HCA Embryo Foetal WSSS Dev RNA","abstract":"\"We propose to generate an in-depth single cell and spatial atlas of human embryos during late organogenesis, at 6/7 post conception weeks (PCW). We will deploy genomics technologies to profile single cells from dissociated tissues and within intact tissue sections, and deploy cutting-edge computational methods to reconstruct, in silico, a three-dimensional atlas of the whole human embryo. \n\nDetailed single cell atlas of whole human embryos\nDeliverables: Complete whole embryo atlas datasets by high-throughput genomics profiling (single cell RNA-sequencing (scRNA-seq), single nuclear RNA-sequencing (snRNA-seq), and accessible chromatin sequencing (ATAC-seq)); and spatial transcriptomics (ST, e.g. 10x Genomics Visium), in situ sequencing (ISS) and multiplex smFISH analysis of tissue sections.\n\"","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005191","title":"Melioidosis_host_transcriptome_I","description":"Melioidosis is a rapidly progressing and frequently fatal disease caused by a bacterium Burkholderia pseudomallei found in soils of tropical and sub-tropical countries. Healthy individuals living in disease hotspots such as northeast Thailand develop serological evidence of exposure from early childhood. However, not all exposure leads to disease, suggesting that there may be bacterial, host, or environmental factors that influence the disease outcome. For \"Melioidosis Transcriptome\" study is part of this project to help determine host biomarkers associated with melioidosis and disease outcomes. As diabetes mellitus is a major predisposing risk factor for melioidosis, we will also test whether the host biomarkers are modulated by host diabetic condition. \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This project aims to understand how human host respond to Melioidosis infection and whether host diabetes status, which is one of the major risk factor could modulate the infection outcomes.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005192","title":"mouse DNASE1l3 KO","description":"mouse DNASE1l3 KO","abstract":"mouse DNASE1l3 KO","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005193","title":"maternal plasma","description":"maternal plasma","abstract":"maternal plasma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005194","title":"Single cell and plasma RNA sequencing","description":"Single cell and plasma RNA sequencing for RNA liquid biopsy for hepatocellular carcinoma","abstract":"Single cell and plasma RNA sequencing for RNA liquid biopsy for hepatocellular carcinoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-09T02:00:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005195","title":"Disseminated_Tumour_Cells_G_T_seq__neotax_","description":"Disseminated tumour cells isolated from bone marrow of patients with a history of primary breast cancer are subjected to genomic and transcriptomic profiling.","abstract":"Numerous studies have identified that disseminated tumour cells (DTCs) can be isolated from the bone marrow of indiviudals with a history of primary breast cancer. The identification of these cells is associated with a higher risk of future distant metastatic relapse; relapse might be rapid, occur many years later or may never occur at all. In this study we are  investigating whether the molecular features of DTCs can help us to understand the development and progression of cancer.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005196","title":"Whole genome sequence and RNA-seq data from paired tumour and germline samples from mesothelioma patients.","description":"Malignant pleural mesothelioma (MPM) has a poor overall survival with few treatment options. Whole genome sequencing (WGS) combined with RNA sequencing (RNA-seq) analysis of the immune features of MPM offers the prospect of identifying changes that could inform future clinical trials. We analysed somatic mutation and RNA-seq data from 229 MPM samples, including 58 MPM samples that had undergone WGS from our own institutions, together with other published data. This combined analysis identified somatic driver genes, including newly identified candidate genes. Whole genome doubling was a frequent event that correlated with shorter survival. Mutational signature analysis revealed dominant signatures and showed that defects in homologous recombination repair were infrequent in our cohort. Within the tumour immune environment we identified high M2 macrophage infiltrate linked with MMP2, MMP14, TGFB1 and CCL2 expression, representing an immunosuppressive environment. A small subset of samples had a higher proportion of CD8 T cells and a high cytolytic score, suggesting a ‘hot’ immune environment which is independent of the somatic mutations. We propose that our findings on genomic changes and subtypes of immune microenvironments may influence therapeutic planning in the future.","abstract":"Malignant pleural mesothelioma (MPM) has a poor overall survival with few treatment options. Whole genome sequencing (WGS) combined with RNA sequencing (RNA-seq) analysis of the immune features of MPM offers the prospect of identifying changes that could inform future clinical trials. We analysed somatic mutation and RNA-seq data from 229 MPM samples, including 58 MPM samples that had undergone WGS from our own institutions, together with other published data. This combined analysis identified somatic driver genes, including newly identified candidate genes. Whole genome doubling was a frequent event that correlated with shorter survival. Mutational signature analysis revealed dominant signatures and showed that defects in homologous recombination repair were infrequent in our cohort. Within the tumour immune environment we identified high M2 macrophage infiltrate linked with MMP2, MMP14, TGFB1 and CCL2 expression, representing an immunosuppressive environment. A small subset of samples had a higher proportion of CD8 T cells and a high cytolytic score, suggesting a ‘hot’ immune environment which is independent of the somatic mutations. We propose that our findings on genomic changes and subtypes of immune microenvironments may influence therapeutic planning in the future.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-12T05:55:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005197","title":"arrayCGH for copy number profiling on tumor DNA from pediatric cancer tissue samples","description":"This dataset contains arrayCGH (HumanCytoSNP 850k and HumanCytoSNP v12.1) data from tumor DNA samples of various pediatric cancer entities. Files are provided in IDAT format and as text files processed with GenomeStudio 2.0.","abstract":"This dataset contains arrayCGH (HumanCytoSNP 850k and HumanCytoSNP v12.1) data from tumor DNA samples of various pediatric cancer entities. Files are provided in IDAT format and as text files processed with GenomeStudio 2.0.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-12T08:31:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005198","title":"sWGS on cfDNA and matching tumor DNA in pediatric cancer","description":"This dataset contains shallow whole genome sequencing data from paired cfDNA - tumor DNA samples of various pediatric cancer entities. Files are provided in fastq format. Samples were sequenced on an Ion Proton sequencer (Thermo Fisher Scientific) or a Hiseq3000 (Illumina). Data analysis is available at https://github.com/rmvpaeme/sWGS_pediatric_cancer.","abstract":"This dataset contains shallow whole genome sequencing data from paired cfDNA - tumor DNA samples of various pediatric cancer entities. Files are provided in fastq format. Samples were sequenced on an Ion Proton sequencer (Thermo Fisher Scientific) or a Hiseq3000 (Illumina). Data analysis is available at https://github.com/rmvpaeme/sWGS_pediatric_cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-12T09:24:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005199","title":"Paired exome and low-coverage genome sequencing of osteosarcoma","description":"We perform longitudinal genome-sequencing analysis of 12 patients with metastatic or refractory osteosarcoma. The study was approved at the University Hospital Basel, following the approval of the ethical committee for mutational analysis of anonymized samples (“Ethikkommission beider Basel” ref. 274/12). All tumor samples were evaluated by an experienced bone pathologist to confirm the diagnosis.","abstract":"We perform longitudinal genome-sequencing analysis of 12 patients with metastatic or refractory osteosarcoma. The study was approved at the University Hospital Basel, following the approval of the ethical committee for mutational analysis of anonymized samples (“Ethikkommission beider Basel” ref. 274/12). All tumor samples were evaluated by an experienced bone pathologist to confirm the diagnosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-12T09:58:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005200","title":"GWAS identifies different pigmentation risk loci for high-risk, monosomy 3 and low-risk, disomy 3 uveal melanomas","description":null,"abstract":"Uveal melanoma (UM), a rare malignant tumor of the eye, is predominantly observed in populations of European ancestry. UM clinical outcome depends on the mutational status of UM: tumors carrying a monosomy 3 (M3) and with BAP1 inactivation frequently relapse mainly in the liver, whereas UM with disomy 3 (D3) and SF3B1 or EIF1AX mutations are associated with rare and late liver metastasis. Our genome-wide association study (GWAS) of 1,142 UM patients of European ancestry confirms the previously identified risk locus on chromosome 5p15.33 on CLPTM1L (rs421284: odds ratio (OR)=1.58 [1.35 1.86]; p=2.0×10-8), and identifies two additional risk loci involved in eye pigmentation, the IRF4 locus on chromosome 6 (rs12203592: OR=1.76 [1.44 2.16]; p=3.6×10-8) and the HERC2 locus on chromosome 15 (rs12913832; OR=0.57 [0.48 0.67]; p=1.9×10-11). By adding eye color as determined by the IrisPlex system as a covariate, we demonstrate that the IRF4 locus remains significant, suggesting risk at this locus may be partly explained by other biological functions independent of eye pigmentation. Finally, when UM cases were stratified according to their chromosome 3 status, IRF4 rs12203592 SNP was found to be exclusively associated with risk for D3 UM subtype (ORD3=2.73 [1.87 3.97], p=1.8×10-7), the HERC2 rs12913832 SNP was exclusively associated with risk for M3 UM subtype (ORM3=2.43 [1.79-3.29], p=1.1×10-8), while the CLPTM1L risk locus remained equally significant in both subgroups. These results strongly suggest that UM tumor biology and metastatic potential is influenced by at least two distinct genetic backgrounds which include a unique germline and somatic components.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005201","title":"The T cell receptor repertoire of tumor infiltrating T cells is predictive and prognostic for cancer survival","description":"Tumor infiltration by T cells is paramount for effective anti-cancer immune responses. We hypothesized that the T cell receptor (TCR) repertoire of tumor infiltrating T lymphocytes (TIL/Tc) could determine disease course at different stages in cancer progression. We show that the diversity of the TIL/Tc TCR at baseline is prognostic in various cancers, whereas in metastatic melanoma TIL/Tc TCR clonality at baseline is predictive for activity and efficacy of PD1 blockade immunotherapy.","abstract":"Tumor infiltration by T cells is paramount for effective anti-cancer immune responses. We hypothesized that the T cell receptor (TCR) repertoire of tumor infiltrating T lymphocytes (TIL/Tc) could determine disease course at different stages in cancer progression. We show that the diversity of the TIL/Tc TCR at baseline is prognostic in various cancers, whereas in metastatic melanoma TIL/Tc TCR clonality at baseline is predictive for activity and efficacy of PD1 blockade immunotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-12T12:51:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005202","title":"mRNA capture sequencing and RT-qPCR for the detection of pathognomonic, novel and secondary fusion transcripts in formalin-fixed paraffin-embedded tissue: a sarcoma showcase","description":"RNA sequencing is widely used to study gene abundance patterns, but less frequently to assess structural alterations such as fusion transcripts. In this study, we assess the performance of messenger RNA (mRNA) capture sequencing to identify fusion transcripts in formalin-fixed paraffin-embedded (FFPE) tissue of different types of sarcoma, followed by orthogonal confirmation using RT-qPCR. To validate our workflow, we used the TruSight RNA Pan-Cancer Panel to analyze a first cohort of 6 positive control tumors for which the diagnostic workup demonstrated the presence of a specific chromosomal rearrangement. Fusion transcript calling by FusionCatcher confirmed all known aberrations and enabled the identification of both fusion gene partners and breakpoints. Next, whole transcriptome TruSeq RNA Exome sequencing was applied to a second cohort of 17 patients, diagnosed with fusion gene-negative alveolar rhabdomyosarcoma (ARMS) or undifferentiated round cell sarcoma (URCS), for whom fluorescence in situ hybridization (FISH) did not identify the classical pathognomonic rearrangements. Remarkably, for 6 out of 17 patients, mRNA capture sequencing readily detected a pathognomonic fusion transcript, i.e. PAX3-FOXO1 in 2 ARMS patients, and EWSR1-FLI1, EWSR1-ERG or EWSR1-NFATC2 in 4 URCS patients. These data show that RNA capture sequencing may enhance the detection rate of pathognomonic fusion genes in sarcoma. For the 11 patients with no known pathognomonic fusion transcript, 11 newly identified fusion transcripts were confirmed by RT-qPCR, including COPS3-TOM1L2, NCOA1-DTNB, WWTR1-LINC01986, PLAA-MOB3B, AP1B1-CHEK2 and BRD4-LEUTX fusion transcripts in ARMS patients. Additionally, recurrently detected secondary fusion transcripts in two patients diagnosed with EWSR1-NFATC2-positive sarcoma were confirmed (COPS4-TBC1D9, PICALM-SYTL2, SMG6-VPS53 and UBE2F-ALS2). Our results provide new insights into the underlying genetic causes of these malignancies.","abstract":"RNA sequencing is widely used to study gene abundance patterns, but less frequently to assess structural alterations such as fusion transcripts. In this study, we assess the performance of messenger RNA (mRNA) capture sequencing to identify fusion transcripts in formalin-fixed paraffin-embedded (FFPE) tissue of different types of sarcoma, followed by orthogonal confirmation using RT-qPCR. To validate our workflow, we used the TruSight RNA Pan-Cancer Panel to analyze a first cohort of 6 positive control tumors for which the diagnostic workup demonstrated the presence of a specific chromosomal rearrangement. Fusion transcript calling by FusionCatcher confirmed all known aberrations and enabled the identification of both fusion gene partners and breakpoints. Next, whole transcriptome TruSeq RNA Exome sequencing was applied to a second cohort of 17 patients, diagnosed with fusion gene-negative alveolar rhabdomyosarcoma (ARMS) or undifferentiated round cell sarcoma (URCS), for whom fluorescence in situ hybridization (FISH) did not identify the classical pathognomonic rearrangements. Remarkably, for 6 out of 17 patients, mRNA capture sequencing readily detected a pathognomonic fusion transcript, i.e. PAX3-FOXO1 in 2 ARMS patients, and EWSR1-FLI1, EWSR1-ERG or EWSR1-NFATC2 in 4 URCS patients. These data show that RNA capture sequencing may enhance the detection rate of pathognomonic fusion genes in sarcoma. For the 11 patients with no known pathognomonic fusion transcript, 11 newly identified fusion transcripts were confirmed by RT-qPCR, including COPS3-TOM1L2, NCOA1-DTNB, WWTR1-LINC01986, PLAA-MOB3B, AP1B1-CHEK2 and BRD4-LEUTX fusion transcripts in ARMS patients. Additionally, recurrently detected secondary fusion transcripts in two patients diagnosed with EWSR1-NFATC2-positive sarcoma were confirmed (COPS4-TBC1D9, PICALM-SYTL2, SMG6-VPS53 and UBE2F-ALS2). Our results provide new insights into the underlying genetic causes of these malignancies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-12T12:51:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005203","title":"The distinct DNA methylome of acute lymphoblastic leukemia","description":"Here, using whole genome bisulfite sequencing (WGBS) data of over one hundred patients from multiple subtypes of acute lymphoblastic leukemia (ALL), controls samples and ALL cell lines, we show that in contrast to the prevailing paradigm, ALL samples exhibit CpG island hypermethylation but little to no global loss of methylation. The subtype-specific CpG island hypermethylation levels in T cell ALL span a broad range of methylation levels rather than previous binary classifications and are influenced by multiple factors, including TET2 expression.","abstract":"Here, using whole genome bisulfite sequencing (WGBS) data of over one hundred patients from multiple subtypes of acute lymphoblastic leukemia (ALL), controls samples and ALL cell lines, we show that in contrast to the prevailing paradigm, ALL samples exhibit CpG island hypermethylation but little to no global loss of methylation. The subtype-specific CpG island hypermethylation levels in T cell ALL span a broad range of methylation levels rather than previous binary classifications and are influenced by multiple factors, including TET2 expression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-14T16:46:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005204","title":"Dissecting the Spatial Heterogeneity of Single Circulating Tumor Cells in Hepatocellular Carcinoma","description":"The dismal outcome of hepatocellular carcinoma (HCC) is closely associated with intra- and extrahepatic metastases, which have been proposed to be initiated by circulating tumor cells (CTCs). However, the plasticity of gene expression and immune evasion mechanisms of CTCs during systemic circulation are not well defined. Here, we determined intra- and inter-vascular transcriptional heterogeneity within the circulatory system using single-cell RNA-sequencing of 113 CTCs isolated from four key vascular sites along their dissemination route in ten HCC patients.","abstract":"The dismal outcome of hepatocellular carcinoma (HCC) is closely associated with intra- and extrahepatic metastases, which have been proposed to be initiated by circulating tumor cells (CTCs). However, the plasticity of gene expression and immune evasion mechanisms of CTCs during systemic circulation are not well defined. Here, we determined intra- and inter-vascular transcriptional heterogeneity within the circulatory system using single-cell RNA-sequencing of 113 CTCs isolated from four key vascular sites along their dissemination route in ten HCC patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-15T07:36:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005205","title":"Whole-Exome Sequences from Imazighen and non-Imazghen from Tunisia","description":"Study of high-coverage whole-exome sequences from Amazigh (Tamazight-speakers) and non-Amazigh individuals (Arab-speakers) from Tunisia to analyze the impact of demography in functional genomic variation in the complex demographic context of North Africa. Amazigh individuals were sampled in Chenini and Douiret, and non-Amazigh individuals were sampled in Tunis.","abstract":"Study of high-coverage whole-exome sequences from Amazigh (Tamazight-speakers) and non-Amazigh individuals (Arab-speakers) from Tunisia to analyze the impact of demography in functional genomic variation in the complex demographic context of North Africa. Amazigh individuals were sampled in Chenini and Douiret, and non-Amazigh individuals were sampled in Tunis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-15T07:46:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005206","title":"High titers and low fucosylation of early phase anti-SARS-CoV-2 IgG promote hyper-inflammation by alveolar macrophages","description":"We show that early phase anti-Spike IgG in serum of critically ill COVID-19 patients induces hyper-inflammatory responses by human alveolar macrophages. We identified that this excessive inflammatory response is dependent on two antibody features that are specific for severe COVID-19. First, inflammation is driven by high titers of anti-Spike IgG, a hallmark of severe disease. Second, we found that anti-Spike IgG from severely ill patients is intrinsically more pro-inflammatory because of different glycosylation of the Fc tail, particularly by low fucosylation. \nThis dataset is linked with the following ArrayExpress Experiment: E-MTAB-10431 - 2020_COVID19_FCGR_MIL10_IgGfucosylation","abstract":"We show that early phase anti-Spike IgG in serum of critically ill COVID-19 patients induces hyper-inflammatory responses by human alveolar macrophages. We identified that this excessive inflammatory response is dependent on two antibody features that are specific for severe COVID-19. First, inflammation is driven by high titers of anti-Spike IgG, a hallmark of severe disease. Second, we found that anti-Spike IgG from severely ill patients is intrinsically more pro-inflammatory because of different glycosylation of the Fc tail, particularly by low fucosylation. \nThis dataset is linked with the following ArrayExpress Experiment: E-MTAB-10431 - 2020_COVID19_FCGR_MIL10_IgGfucosylation","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-15T08:53:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005207","title":"HSC_population_dynamics___KX001_samples___methylseq","description":"Whole genome methylation sequencing of blood colonies derived from sorted HSCs of healthy donors.","abstract":"Whole genome methylation sequencing of blood colonies derived from sorted HSCs of healthy donors.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005208","title":"WGMS_MPN_PD5163","description":"Whole genome methylation sequencing of colonies of patients with myeloproliferative neoplasms.","abstract":"Whole genome methylation sequencing of colonies of patients with myeloproliferative neoplasms.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005209","title":"WGMS_MPN_PD5182","description":"Whole genome methylation sequencing of colonies of patients with myeloproliferative neoplasms.","abstract":"Whole genome methylation sequencing of colonies of patients with myeloproliferative neoplasms.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005210","title":"WGMS_MPN_PD5847","description":"Whole genome methylation sequencing of colonies of patients with myeloproliferative neoplasms.","abstract":"Whole genome methylation sequencing of colonies of patients with myeloproliferative neoplasms.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005211","title":"WGMS_MPN_PD6629","description":"Whole genome methylation sequencing of colonies of patients with myeloproliferative neoplasms.","abstract":"Whole genome methylation sequencing of colonies of patients with myeloproliferative neoplasms.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005214","title":"Sclerosing epithelioid fibrosarcoma case report","description":"Sclerosing epithelioid fibrosarcoma (SEF) is a rare and aggressive soft tissue sarcomathought  to originate in fibroblasts of the tissues surrounding tendons, ligaments and muscles. Minimally responsive to conventional cytotoxic chemotherapies, greater than 50% of SEF patients experience relapse and/or metastatic disease. SEF is most commonly discovered in middle-aged and elderly adults, but also rarely in children. A common gene fusion occurring between the EWSR1 and CREB3L1 genes has been observed in 80-90% of SEF cases. We describe here the youngest SEF patient reported to date (a 3-year-old Caucasian male) who presented with numerous bony and lung metastases. Additionally, we perform a comprehensive literature review of all SEF-related articles published since the disease was first characterized. The patient described in this report experienced persistent disease progression despite being heavily treated\nwith multiple surgeries, radiation, numerous chemotherapies and targeted therapeutics. Primary tumor, metastatic and relapse sites were sequenced by whole genome, whole exome, and deep transcriptome next generation sequencing with comparison to a patient-matched normal blood sample. Consistent across all sequencing analyses was the disease-defining EWSR1-CREB3L1 fusion as a single feature consensus. We provide an analysis of our genomic findings and a discussion as to potential therapeutic strategies for SEF.","abstract":"Sclerosing epithelioid fibrosarcoma (SEF) is a rare and aggressive soft tissue sarcomathought  to originate in fibroblasts of the tissues surrounding tendons, ligaments and muscles. Minimally responsive to conventional cytotoxic chemotherapies, greater than 50% of SEF patients experience relapse and/or metastatic disease. SEF is most commonly discovered in middle-aged and elderly adults, but also rarely in children. A common gene fusion occurring between the EWSR1 and CREB3L1 genes has been observed in 80-90% of SEF cases. We describe here the youngest SEF patient reported to date (a 3-year-old Caucasian male) who presented with numerous bony and lung metastases. Additionally, we perform a comprehensive literature review of all SEF-related articles published since the disease was first characterized. The patient described in this report experienced persistent disease progression despite being heavily treated\nwith multiple surgeries, radiation, numerous chemotherapies and targeted therapeutics. Primary tumor, metastatic and relapse sites were sequenced by whole genome, whole exome, and deep transcriptome next generation sequencing with comparison to a patient-matched normal blood sample. Consistent across all sequencing analyses was the disease-defining EWSR1-CREB3L1 fusion as a single feature consensus. We provide an analysis of our genomic findings and a discussion as to potential therapeutic strategies for SEF.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-15T19:11:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005215","title":"Sclerosing epithelioid fibrosarcoma case report","description":"Sclerosing epithelioid fibrosarcoma (SEF) is a rare and aggressive soft tissue sarcomathought  to originate in fibroblasts of the tissues surrounding tendons, ligaments and muscles. Minimally responsive to conventional cytotoxic chemotherapies, greater than 50% of SEF patients experience relapse and/or metastatic disease. SEF is most commonly discovered in middle-aged and elderly adults, but also rarely in children. A common gene fusion occurring between the EWSR1 and CREB3L1 genes has been observed in 80-90% of SEF cases. We describe here the youngest SEF patient reported to date (a 3-year-old Caucasian male) who presented with numerous bony and lung metastases. Additionally, we perform a comprehensive literature review of all SEF-related articles published since the disease was first characterized. The patient described in this report experienced persistent disease progression despite being heavily treated\nwith multiple surgeries, radiation, numerous chemotherapies and targeted therapeutics. Primary tumor, metastatic and relapse sites were sequenced by whole genome, whole exome, and deep transcriptome next generation sequencing with comparison to a patient-matched normal blood sample. Consistent across all sequencing analyses was the disease-defining EWSR1-CREB3L1 fusion as a single feature consensus. We provide an analysis of our genomic findings and a discussion as to potential therapeutic strategies for SEF.","abstract":"Sclerosing epithelioid fibrosarcoma (SEF) is a rare and aggressive soft tissue sarcomathought  to originate in fibroblasts of the tissues surrounding tendons, ligaments and muscles. Minimally responsive to conventional cytotoxic chemotherapies, greater than 50% of SEF patients experience relapse and/or metastatic disease. SEF is most commonly discovered in middle-aged and elderly adults, but also rarely in children. A common gene fusion occurring between the EWSR1 and CREB3L1 genes has been observed in 80-90% of SEF cases. We describe here the youngest SEF patient reported to date (a 3-year-old Caucasian male) who presented with numerous bony and lung metastases. Additionally, we perform a comprehensive literature review of all SEF-related articles published since the disease was first characterized. The patient described in this report experienced persistent disease progression despite being heavily treated\nwith multiple surgeries, radiation, numerous chemotherapies and targeted therapeutics. Primary tumor, metastatic and relapse sites were sequenced by whole genome, whole exome, and deep transcriptome next generation sequencing with comparison to a patient-matched normal blood sample. Consistent across all sequencing analyses was the disease-defining EWSR1-CREB3L1 fusion as a single feature consensus. We provide an analysis of our genomic findings and a discussion as to potential therapeutic strategies for SEF.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-15T19:27:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005216","title":"Novel optineurin frameshift insertion causing familial frontotemporal dementia and parkinsonism without amyotrophic lateral sclerosis","description":"Novel optineurin frameshift insertion causing familial frontotemporal dementia and parkinsonism without amyotrophic lateral sclerosis","abstract":"Novel optineurin frameshift insertion causing familial frontotemporal dementia and parkinsonism without amyotrophic lateral sclerosis","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005217","title":"Sequencing_study_of_PBMCs_from_individuals_that_have_received_the_Covid_vaccine","description":"Sequencing study of PBMCs from individuals that have received the Covid vaccine","abstract":"Sequencing study of PBMCs from individuals that have received the Covid vaccine","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005218","title":"Asymetric_distrbution_of_immune_cells_in_murine_toungue","description":"Sequencing study of the spatial differences in the murine tongue","abstract":"Murine Tongues were dissected into multiple regions to determine spatial differences using RNASeq.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005219","title":"Role_of_AREG_in_development_of_Fibrosis_in_a_mouse_model_of_UTI","description":"Sequencing study of the effect of AREG in the development of infection dependent fibrosis.","abstract":"Either WT or AREG KO mice were given a UTI and the kidneys taken 4 weeks later to examine the development of fibrosis.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005220","title":"Novel optineurin frameshift insertion causing familial frontotemporal dementia and parkinsonism without amyotrophic lateral sclerosis","description":"Frontotemporal Dementia (FTD) is a common cause of Young Onset Dementia and has diverse clinical manifestations involving behaviour, executive function, language and motor function, including parkinsonism. Up to 50% of FTD patients report a positive family history, supporting a strong genetic basis, particularly in cases with both FTD and amyotrophic lateral sclerosis (FTD-ALS). Mutations in three genes are associated with the majority of familial FTD (fFTD) cases - microtubule associated protein tau gene (MAPT), progranulin gene (PGRN), and hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72), whilst mutations in other genes such as optineurin (OPTN) have rarely been reported. Mutations in OPTN have been reported mostly in familial and sporadic cases of ALS, or in rare cases of FTD-ALS, but not in association with pure or predominant FTD and/or parkinsonian phenotype. Here, we report for the first time, a family from the Philippines with 4 affected members harbouring the same OPTN frameshift insertion, presenting with FTD-related phenotypes, including one sibling with predominant parkinsonism resembling corticobasal syndrome. Notably, none of the affected members showed any evidence of motor neuron disease or ALS at the time of writing, both clinically and on electrophysiological testing, expanding the phenotypic spectrum of OPTN mutations. Close follow-up of mutation carriers for the development of new clinical features and wider investigation of additional family members with further genetic analyses will be conducted to investigate the possibility of other genetic modifiers in this family which could explain phenotypic heterogeneity.","abstract":"Frontotemporal Dementia (FTD) is a common cause of Young Onset Dementia and has diverse clinical manifestations involving behaviour, executive function, language and motor function, including parkinsonism. Up to 50% of FTD patients report a positive family history, supporting a strong genetic basis, particularly in cases with both FTD and amyotrophic lateral sclerosis (FTD-ALS). Mutations in three genes are associated with the majority of familial FTD (fFTD) cases - microtubule associated protein tau gene (MAPT), progranulin gene (PGRN), and hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72), whilst mutations in other genes such as optineurin (OPTN) have rarely been reported. Mutations in OPTN have been reported mostly in familial and sporadic cases of ALS, or in rare cases of FTD-ALS, but not in association with pure or predominant FTD and/or parkinsonian phenotype. Here, we report for the first time, a family from the Philippines with 4 affected members harbouring the same OPTN frameshift insertion, presenting with FTD-related phenotypes, including one sibling with predominant parkinsonism resembling corticobasal syndrome. Notably, none of the affected members showed any evidence of motor neuron disease or ALS at the time of writing, both clinically and on electrophysiological testing, expanding the phenotypic spectrum of OPTN mutations. Close follow-up of mutation carriers for the development of new clinical features and wider investigation of additional family members with further genetic analyses will be conducted to investigate the possibility of other genetic modifiers in this family which could explain phenotypic heterogeneity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-16T10:43:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005221","title":"Molecular characterization of Barrett’s esophagus at single cell resolution","description":"Backgrounds &amp; Aims: Patient with Barrett’s esophagus (BE) have an increased risk to develop esophageal adenocarcinoma and are under periodical endoscopic surveillance for malignant transformation. Pathologists distinguish between different BE stages to identify high-risk patients, but this process remains difficult as stage-specific markers are still missing. We established BE organoid cultures, applied single cell sequencing approaches to identify differences in gene expression and genomic alterations, and validated candidate genes for their predictive value on histological sections. Methods: We collected 43 epithelial biopsies from 21 patients, established organoids for the clonal expansion of matching healthy and diseased tissue from two patients to identify genomic alterations by whole genome sequencing (WGS). We performed single cell DNA-sequencing (scDNAseq) to analyse DNA alterations within biopsies from 8 patients and single cell RNA-sequencing (scRNAseq) to identify gene expression differences between BE stages from 19 patients. Candidate marker genes were then validated by RNA in situ hybridization experiments on histological resection specimen. Results: Most BE biopsies were chromosomal stable (CS) and their single base substitution (SBS) signatures were indistinguishable from the healthy control tissues. Dysplastic BE cells contained areas of chromosomal instabilities (CIN), which differed by the presence of the SBS17 signatures from biopsy-matching CS cells or patient-matching healthy control cells. Such CIN areas affected efficient clustering of the scRNAseq data. We identified two sets of marker genes (SLC5A5, PSCA, LIPF and ANPEP, CEACAM6, REG4), which distinguish columnar BE epithelium from non-dysplastic/dysplastic stages. CLDN2 allowed the distinction between dysplastic and more advanced stages as its expression level increased and spread in dysplastic BE glands. Conclusions: Molecular characterization of BE samples identified a correlation between the presence of CIN and COSMIC signature 17, and we report seven marker genes that help in distinguishing different BE stages.","abstract":"Backgrounds &amp; Aims: Patient with Barrett’s esophagus (BE) have an increased risk to develop esophageal adenocarcinoma and are under periodical endoscopic surveillance for malignant transformation. Pathologists distinguish between different BE stages to identify high-risk patients, but this process remains difficult as stage-specific markers are still missing. We established BE organoid cultures, applied single cell sequencing approaches to identify differences in gene expression and genomic alterations, and validated candidate genes for their predictive value on histological sections. Methods: We collected 43 epithelial biopsies from 21 patients, established organoids for the clonal expansion of matching healthy and diseased tissue from two patients to identify genomic alterations by whole genome sequencing (WGS). We performed single cell DNA-sequencing (scDNAseq) to analyse DNA alterations within biopsies from 8 patients and single cell RNA-sequencing (scRNAseq) to identify gene expression differences between BE stages from 19 patients. Candidate marker genes were then validated by RNA in situ hybridization experiments on histological resection specimen. Results: Most BE biopsies were chromosomal stable (CS) and their single base substitution (SBS) signatures were indistinguishable from the healthy control tissues. Dysplastic BE cells contained areas of chromosomal instabilities (CIN), which differed by the presence of the SBS17 signatures from biopsy-matching CS cells or patient-matching healthy control cells. Such CIN areas affected efficient clustering of the scRNAseq data. We identified two sets of marker genes (SLC5A5, PSCA, LIPF and ANPEP, CEACAM6, REG4), which distinguish columnar BE epithelium from non-dysplastic/dysplastic stages. CLDN2 allowed the distinction between dysplastic and more advanced stages as its expression level increased and spread in dysplastic BE glands. Conclusions: Molecular characterization of BE samples identified a correlation between the presence of CIN and COSMIC signature 17, and we report seven marker genes that help in distinguishing different BE stages.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-16T12:52:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005222","title":"Molecular characterization of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis","description":"Patients with hepatocellular carcinoma (HCC) associated to non-alcoholic steatohepatitis (NASH) are increasing globally, but their molecular traits are not well characterized. Our molecular characterization revealed higher rates of ACVR2A mutations (10%) – a potential tumour suppressor, presence of a novel mutational signature (MutSig-NASH-HCC), a more relevant role of Wnt/TGF-β proliferation subclass in tumours (42%) and immunosuppressive traits in the adjacent non-tumoral tissue.","abstract":"Patients with hepatocellular carcinoma (HCC) associated to non-alcoholic steatohepatitis (NASH) are increasing globally, but their molecular traits are not well characterized. Our molecular characterization revealed higher rates of ACVR2A mutations (10%) – a potential tumour suppressor, presence of a novel mutational signature (MutSig-NASH-HCC), a more relevant role of Wnt/TGF-β proliferation subclass in tumours (42%) and immunosuppressive traits in the adjacent non-tumoral tissue.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-16T14:23:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005223","title":"Extracellular transcriptome of seminal plasma","description":null,"abstract":"A diagnostic non-invasive biomarker test for prostate cancer at an early stage, with high sensitivity and specificity, would improve diagnostic decision making. Extracellular RNAs present in seminal plasma might contain biomarker potential for the accurate detection of clinically significant prostate cancer. So far, the extracellular messenger RNA (mRNA) profile of seminal plasma has not been interrogated for its biomarker potential in the context of prostate cancer. Here, we investigate the mRNA transcriptome in seminal plasma samples obtained from prostate cancer patients (n=25), patients with benign prostate hyperplasia (n=26) and individuals without prostatic disease (n=6). Seminal plasma harbors a complex mRNA repertoire that reflects prostate as its tissue of origin. The endogenous RNA content is higher in the prostate cancer samples compared to the control samples. Prostate cancer antigen 3 (PCA3), a long non-coding RNA with prostate cancer-specific overexpression, and ATP-binding cassette transporter 1 (ABCA1), known to be involved in the prostate cancer pathogenesis, were more abundant in the prostate cancer group. In addition, twelve high confidence fusion transcripts could be detected in prostate cancer samples, including the bona-fide prostate cancer fusion transcript TMPRSS2-ERG. Our findings provide proof-of-principle that the extracellular transcriptome of seminal plasma can reveal information of an underlying prostate cancer.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005224","title":"Esophageal Adenocarcinoma Organoid Genomics","description":"Single cell RNA-seq (scRNA-seq) of esophageal adenocarcinoma organoids to benchmark variant calling from 10X Genomics scRNA-seq data. Five EAC organoids were subjected to scRNA-seq and two included matched exome data.","abstract":"Single cell RNA-seq (scRNA-seq) of esophageal adenocarcinoma organoids to benchmark variant calling from 10X Genomics scRNA-seq data. Five EAC organoids were subjected to scRNA-seq and two included matched exome data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-16T15:00:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005225","title":"Gluten-free microbiome study UMCG","description":null,"abstract":"Gluten-free diet intervention: 11 individuals, 3 time points (T1: 1 week before intervention, T2: at the intervention; T3: 5 weeks after intervention. Fecal samples taken at each time point were sujbject of VLP enrichment and routine metagenomics sequencing","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-18T19:43:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005226","title":"Splicing patterns in SF3B1 mutated uveal melanoma generate shared immunogenic tumor-specific neo-epitopes","description":"Disruption of splicing patterns due to mutations of genes coding splicing factors in tumors represents a potential source of tumor neo-antigens, which would be both public (shared between patients) and tumor-specific (not expressed in normal tissues). In this study, we show that mutations of the splicing factor SF3B1 in uveal melanoma (UM) generate such immunogenic neo-antigens. Memory CD8+ T cells specific for these neo-antigens are preferentially found in 20% of UM patients bearing SF3B1 mutated tumors. Single cell analyses of neo-epitope specific T cells from the blood identified large clonal T cell expansions, with distinct effector transcription patterns. Some of these expanded TCRs are also present in the corresponding tumors. CD8+ T cell clones specific for the neo-epitopes specifically recognize and kill SF3B1-mutated tumor cells, supporting the use of this new family of neo-antigens as therapeutic targets.","abstract":"Disruption of splicing patterns due to mutations of genes coding splicing factors in tumors represents a potential source of tumor neo-antigens, which would be both public (shared between patients) and tumor-specific (not expressed in normal tissues). In this study, we show that mutations of the splicing factor SF3B1 in uveal melanoma (UM) generate such immunogenic neo-antigens. Memory CD8+ T cells specific for these neo-antigens are preferentially found in 20% of UM patients bearing SF3B1 mutated tumors. Single cell analyses of neo-epitope specific T cells from the blood identified large clonal T cell expansions, with distinct effector transcription patterns. Some of these expanded TCRs are also present in the corresponding tumors. CD8+ T cell clones specific for the neo-epitopes specifically recognize and kill SF3B1-mutated tumor cells, supporting the use of this new family of neo-antigens as therapeutic targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-19T14:26:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005227","title":"Single-cell landscapes of primary glioblastomas and matched organoids and cell lines reveal variable retention of inter- and intra-tumor heterogeneity","description":"Glioblastomas (GBMs) are aggressive primary malignant brain tumors characterized by extensive levels of inter- and intra-tumor genetic and phenotypic heterogeneity. Patient-derived organoids (PDOs) have recently emerged as useful models to study such heterogeneity. Here, we present bulk exome as well as single-cell genome and transcriptome profiles of primary IDH wild type GBMs from ten patients, including two recurrent tumors, as well as PDOs and brain tumor-initiating cell (BTIC) lines derived from these patients. We find that PDOs are genetically similar to and variably retain gene expression characteristics of their parent tumors. At the phenotypic level, PDOs appear to exhibit similar levels of transcriptional heterogeneity as their parent tumors, whereas BTIC lines tend to be enriched for cells in a more uniform transcriptional state. The datasets introduced here will provide a valuable resource to help guide experiments using GBM-derived organoids, especially in the context of studying cellular heterogeneity.","abstract":"Glioblastomas (GBMs) are aggressive primary malignant brain tumors characterized by extensive levels of inter- and intra-tumor genetic and phenotypic heterogeneity. Patient-derived organoids (PDOs) have recently emerged as useful models to study such heterogeneity. Here, we present bulk exome as well as single-cell genome and transcriptome profiles of primary IDH wild type GBMs from ten patients, including two recurrent tumors, as well as PDOs and brain tumor-initiating cell (BTIC) lines derived from these patients. We find that PDOs are genetically similar to and variably retain gene expression characteristics of their parent tumors. At the phenotypic level, PDOs appear to exhibit similar levels of transcriptional heterogeneity as their parent tumors, whereas BTIC lines tend to be enriched for cells in a more uniform transcriptional state. The datasets introduced here will provide a valuable resource to help guide experiments using GBM-derived organoids, especially in the context of studying cellular heterogeneity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-20T23:21:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005228","title":"Circulating tumor cells Exome sequencing from breast cancer","description":"Single cell technologies allow interrogating the extent of tumor heterogeneity, providing novel insights into tumor evolution and treatment resistance mechanisms. Here, we investigated the level of genetic heterogeneity among circulating tumor cells (CTCs) at the single nucleotide variation and copy number aberration (CNA) levels and compared it to synchronous matched primary tumor/metastatic lesion from 3 metastatic breast cancer patients with triple-negative (TNBC), HER2-positive (HER2+) and estrogen-receptor-positive (ER+) tumors. Whole exome sequencing was performed on 3 synchronous bulk tumor tissue and 21 single/pooled CTC samples. When comparing bulk tissue with CTCs from the same patient, we found similar CNA profiles and the same patient-specific driver mutations for the HER2+ and TNBC tumors. Different CNA profiles and driver mutations were found for the ER+ tumor, with two distinct clones being identified in the CTCs, one harboring an activating ESR1 mutation, the other one bearing a TP53 mutation. These data suggest that tumor tissue and CTCs provide in a subset of patients complementary clinically relevant information to map tumor heterogeneity and monitor tumor evolution. Further validation is needed.","abstract":"Single cell technologies allow interrogating the extent of tumor heterogeneity, providing novel insights into tumor evolution and treatment resistance mechanisms. Here, we investigated the level of genetic heterogeneity among circulating tumor cells (CTCs) at the single nucleotide variation and copy number aberration (CNA) levels and compared it to synchronous matched primary tumor/metastatic lesion from 3 metastatic breast cancer patients with triple-negative (TNBC), HER2-positive (HER2+) and estrogen-receptor-positive (ER+) tumors. Whole exome sequencing was performed on 3 synchronous bulk tumor tissue and 21 single/pooled CTC samples. When comparing bulk tissue with CTCs from the same patient, we found similar CNA profiles and the same patient-specific driver mutations for the HER2+ and TNBC tumors. Different CNA profiles and driver mutations were found for the ER+ tumor, with two distinct clones being identified in the CTCs, one harboring an activating ESR1 mutation, the other one bearing a TP53 mutation. These data suggest that tumor tissue and CTCs provide in a subset of patients complementary clinically relevant information to map tumor heterogeneity and monitor tumor evolution. Further validation is needed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-21T10:55:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005229","title":"Improved Sezary cell detection and novel insights into immunophenotypic and molecular heterogeneity in Sézary syndrome","description":"We performed a prospective investigation in Sézary syndrome by the application of a standardized multiparameter flow cytometry, FACS-cell sorting, and RNA-sequencing for an in-depth immunophenotypic and transcriptional profiling of Sézary cells.","abstract":"We performed a prospective investigation in Sézary syndrome by the application of a standardized multiparameter flow cytometry, FACS-cell sorting, and RNA-sequencing for an in-depth immunophenotypic and transcriptional profiling of Sézary cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-22T14:39:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005230","title":"The evolutionary dynamics of human colorectal cancer using single-gland spatial multi-omic profiling of DNA, RNA and chromatin.","description":"Deciphering the mechanisms of colorectal cancer growth, progression and dissemination in each individual patient.","abstract":"Deciphering the mechanisms of colorectal cancer growth, progression and dissemination in each individual patient.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-22T15:04:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005231","title":"Sequencing data of Invasive Micropapillary Carcinoma of the Breast","description":null,"abstract":"Invasive micropapillary carcinoma (IMPC) has very high rates of lymphovascular invasion and lymph node metastasis and has been reported in several organs. However, the genomic mechanisms underlying its metastasis are unclear. Here, we perform whole-genome sequencing of tumor cell clusters from primary IMPC and paired axillary lymph node metastases. Cell clusters in multiple lymph node foci arise from a single cell cluster of the primary tumor. We find evidence that the monoclonal metastatic ancestor in primary IMPC shares the copy-number loss of PRDM16 and IGSF9 and the copy number gain of ALDH2. Immunohistochemistry analysis further shows that low expression of IGSF9 and PRDM16 and high expression of ALDH2 are associated with lymph node metastasis and poor survival of patients with IMPC. We expect these genomic and evolutionary profiles to contribute to the accurate diagnosis of IMPC.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005232","title":"Male-biased migration from East Africa introduced pastoralism into southern Africa","description":null,"abstract":"Hunter-gatherer lifestyles dominated the southern African landscape up to ~2,000 years ago, when herding and farming groups started to arrive in the area. Present-day Khoekhoe-speaking Namaqua (or Nama in short) pastoralists show high proportions of East African admixture, linking the East African ancestry with Khoekhoe herders. Most of the other historical Khoekhoe populations have, however, disappeared over the last few centuries. In our study we analyzed genome-wide autosomal and full mitochondrial data from a population who trace their ancestry to the Khoekhoe-speaking Hessequa herders from the southern Cape region of now South Africa.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-23T10:05:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005233","title":"Male-biased migration from East Africa introduced pastoralism into southern Africa","description":null,"abstract":"Hunter-gatherer lifestyles dominated the southern African landscape up to ~2,000 years ago, when herding and farming groups started to arrive in the area. Present-day Khoekhoe-speaking Namaqua (or Nama in short) pastoralists show high proportions of East African admixture, linking the East African ancestry with Khoekhoe herders. Most of the other historical Khoekhoe populations have, however, disappeared over the last few centuries. In our study we analyzed genome-wide autosomal and full mitochondrial data from a population who trace their ancestry to the Khoekhoe-speaking Hessequa herders from the southern Cape region of now South Africa.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005234","title":"The evolution of hematopoietic cells under cancer therapy","description":"Chemotherapies may increase mutagenesis of healthy cells and change the selective pressures in tissues thus influencing their evolution. However, their contributions to the mutation burden and clonal expansions of healthy somatic tissues are not clear. Here, exploiting the mutational footprint of some chemotherapies, we explore their influence on the evolution of hematopoietic cells. Cells of Acute Myeloid Leukemia (AML) secondary to treatment with platinum-based drugs showed the mutational footprint of these drugs, indicating that non-malignant blood cells received chemotherapy mutations. No trace of 5-fluorouracil (5FU) mutational signature was found in AML secondary to exposure to 5FU, suggesting that cells establishing the AML were quiescent during treatment. Using the platinum-based mutational signature as a barcode, we determined that secondary AMLs began their clonal expansion after the start of the cytotoxic treatment. Its absence in clonal hematopoiesis cases is consistent with a clonal expansion that predates the exposure to the cytotoxic agent.","abstract":"Chemotherapies may increase mutagenesis of healthy cells and change the selective pressures in tissues thus influencing their evolution. However, their contributions to the mutation burden and clonal expansions of healthy somatic tissues are not clear. Here, exploiting the mutational footprint of some chemotherapies, we explore their influence on the evolution of hematopoietic cells. Cells of Acute Myeloid Leukemia (AML) secondary to treatment with platinum-based drugs showed the mutational footprint of these drugs, indicating that non-malignant blood cells received chemotherapy mutations. No trace of 5-fluorouracil (5FU) mutational signature was found in AML secondary to exposure to 5FU, suggesting that cells establishing the AML were quiescent during treatment. Using the platinum-based mutational signature as a barcode, we determined that secondary AMLs began their clonal expansion after the start of the cytotoxic treatment. Its absence in clonal hematopoiesis cases is consistent with a clonal expansion that predates the exposure to the cytotoxic agent.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-25T12:23:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005235","title":"Non-coding mutations reveal cancer driver cistromes in luminal breast cancer","description":"Whole-genome sequencing of primary breast tumors enabled the identification of cancer driver genes and non-coding cancer driver plexuses from somatic mutations. However, differentiating between driver and passenger events among non-coding genetic variants remains a challenge to understand the etiology of cancer and inform the delivery of personalized cancer medicine. Herein, we reveal enrichment of non-coding mutations in cis-regulatory elements that cover a subset of transcription factors linked to tumor progression in luminal breast cancers. Using a cohort of 26 primary luminal ER+PR+ breast tumors, we compiled a catalogue of ~100,000 unique cis-regulatory elements from ATAC-seq data. Integrating this catalogue with somatic mutations from 350 publicly available breast tumor whole genomes, we identified four recurrently mutated individual cis-regulatory elements. By then partitioning the non-coding genome into cistromes, defined as the sum of binding sites for a transcription factor, we uncovered cancer driver cistromes for ten transcription factors, namely CTCF, ELF1, ESR1, FOSL2, FOXA1, FOXM1 GATA3, JUND, TFAP2A, and TFAP2C in luminal breast cancer. Nine of these ten transcription factors were shown to be essential for growth in breast cancer, with four exclusive to the luminal subtype. Collectively, we present a strategy to find cancer driver cistromes relying on quantifying the enrichment of non-coding mutations over cis-regulatory elements concatenated into a functional unit drawn from an accessible chromatin catalogue derived from primary cancer tissues.","abstract":"Whole-genome sequencing of primary breast tumors enabled the identification of cancer driver genes and non-coding cancer driver plexuses from somatic mutations. However, differentiating between driver and passenger events among non-coding genetic variants remains a challenge to understand the etiology of cancer and inform the delivery of personalized cancer medicine. Herein, we reveal enrichment of non-coding mutations in cis-regulatory elements that cover a subset of transcription factors linked to tumor progression in luminal breast cancers. Using a cohort of 26 primary luminal ER+PR+ breast tumors, we compiled a catalogue of ~100,000 unique cis-regulatory elements from ATAC-seq data. Integrating this catalogue with somatic mutations from 350 publicly available breast tumor whole genomes, we identified four recurrently mutated individual cis-regulatory elements. By then partitioning the non-coding genome into cistromes, defined as the sum of binding sites for a transcription factor, we uncovered cancer driver cistromes for ten transcription factors, namely CTCF, ELF1, ESR1, FOSL2, FOXA1, FOXM1 GATA3, JUND, TFAP2A, and TFAP2C in luminal breast cancer. Nine of these ten transcription factors were shown to be essential for growth in breast cancer, with four exclusive to the luminal subtype. Collectively, we present a strategy to find cancer driver cistromes relying on quantifying the enrichment of non-coding mutations over cis-regulatory elements concatenated into a functional unit drawn from an accessible chromatin catalogue derived from primary cancer tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-25T19:12:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005236","title":"test python","description":"test python","abstract":"test python","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005237","title":"Whole-genome landscape of adult T-cell leukemia/lymphoma","description":"Whole-genome sequencing (WGS) data of tumor-normal pairs from 139 ATL patients and RNA sequencing (RNA-seq) data of tumors from 28 ATL patients.","abstract":"Whole-genome sequencing (WGS) data of tumor-normal pairs from 139 ATL patients and RNA sequencing (RNA-seq) data of tumors from 28 ATL patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-26T08:06:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005238","title":"Targeted sequencing of follicular lymphoma tumour samples from the UK's Haematological Malignancy Research Network","description":"Follicular lymphoma displays morphological and clinical heterogeneity, underpinned by shared molecular pathogenesis. Mutations in epigenetic regulators alongside t(14;18) have been identified as disease initiating events. Additional mutational diversity suggests disease heterogeneity. Whether this resolves into mechanistically distinct subsets remains an open question. \nTargeted sequencing was applied to an unselected population-based FL cohort  (n=548) diagnosed in a catchment population of ~4 million (14 centers), with full clinical follow-up (n=538) that included 96 DLBCL transformations. We investigated whether molecular subclusters of FL can be identified, and whether mutational data provide predictive information relating to transformation.","abstract":"Follicular lymphoma displays morphological and clinical heterogeneity, underpinned by shared molecular pathogenesis. Mutations in epigenetic regulators alongside t(14;18) have been identified as disease initiating events. Additional mutational diversity suggests disease heterogeneity. Whether this resolves into mechanistically distinct subsets remains an open question. \nTargeted sequencing was applied to an unselected population-based FL cohort  (n=548) diagnosed in a catchment population of ~4 million (14 centers), with full clinical follow-up (n=538) that included 96 DLBCL transformations. We investigated whether molecular subclusters of FL can be identified, and whether mutational data provide predictive information relating to transformation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-26T12:15:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005239","title":"Epithelial ovarian cancer case exome analysis","description":null,"abstract":"The aim of this study is to identify rare, coding germline genetic variation associated with an increased risk of high-grade serous ovarian cancer.  We carried out exome sequencing of germline DNA from 183 patients with high-grade serous epithelial ovarian cancer.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005240","title":"Epithelial ovarian cancer case exome analysis","description":null,"abstract":"The aim of this project was to identify rare, germline coding variation associated with susceptibility to epithelial ovarain canacer","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005241","title":"Single cell sequencing reveals expanded cytotoxic CD4+ T cells and two clusters of peripheral helper T cells in synovial fluid of ACPA+ RA patients","description":null,"abstract":"Rheumatoid arthritis is an autoimmune disease affecting the synovial joints where CD4+ T cells play a pathogenic role. However, a deeper analysis of cytotoxic CD4+ T cells is still lacking, particularly in the context of the recently described peripheral helper T-cell subset (TPH). Here, we show, using 10X-single-cell sequencing and multi-parameter flow cytometry that cytotoxic CD4+ T cells are enriched in synovial fluid (SF) of anti-citrullinated peptides antibody (ACPA)-positive RA patients. We also identify two distinct TPH clusters differentially characterized by the expression of CXCL13 and PRDM1, respectively. Our data reveal that the adhesion G-Protein Coupled Receptor 56 (GPR56), a marker of circulating cytotoxic cells, delineates the TPH CD4+ T-cell subset in SF. At the site of inflammation, GPR56+ CD4+ T cells expressed the tissue-resident memory markers LAG-3, CXCR6, and CD69. Further, TCR clonality analysis revealed that most of the expanded clones in PB and SF are contained within the cytotoxic CD4+ T-cell population. Finally, the detection of common TCRs between the two TPH and cytotoxic CD4+ T cell clusters suggests a common differentiation pathway between these three subsets. Our study provides a better overview of the different pathogenic T-cell subsets at the site of inflammation in ACPA+ RA and suggests GPR56 as a therapeutic target to modulate TPH cells and cytotoxic CD4+ T cell function.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-26T20:28:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005242","title":"Evolutionary trajectories and clonal migration underlying tumor progression and lymph node metastasis in resectable lung cancer","description":null,"abstract":"In this prospective study, targeted deep sequencing was performed on a total of 160 primary tumors (474 regions) and 112 lymph nodes from 125 patients with stage I-III lung cancer (LuCaTH). Progressive evolution at clonal divergence scale was observed while specific driver events were positively selected for clonal sweeps during tumor development. Between-region genetic divergence (BRGD) of tumors were assessed and positively correlated with tumor differentiation. A machine learning algorithm was employed to evaluate clinicopathological and molecular parameters of primary tumors underlying lymph node metastasis.  By analyzing clonal lineages and metastatic trajectories across multiple nodal stations, we unraveled a common sequential LNM seeding pattern but with divergent modes of clonal spread.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-27T04:19:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005243","title":"Radiation-induced gliomas represent H3-/IDH-wild type pediatric gliomas with recurrent PDGFRA amplification and loss of CDKN2A/B","description":"Long-term complications such as radiation-induced second malignancies occur in a subset of patients following radiation-therapy, particularly relevant in pediatric patients due to the long follow-up period in case of survival. Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies such as acute lymphoblastic leukemia (ALL) and medulloblastoma (MB). We perform comprehensive (epi-) genetic and expression profiling of RIGs arising after cranial irradiation for MB (n=23) and ALL (n=9). Our study reveals a unifying molecular signature for the majority of RIGs, with recurrent PDGFRA amplification and loss of CDKN2A/B and an absence of somatic hotspot mutations in genes encoding histone 3 variants or IDH1/2, uncovering diagnostic markers and potentially actionable targets.","abstract":"Long-term complications such as radiation-induced second malignancies occur in a subset of patients following radiation-therapy, particularly relevant in pediatric patients due to the long follow-up period in case of survival. Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies such as acute lymphoblastic leukemia (ALL) and medulloblastoma (MB). We perform comprehensive (epi-) genetic and expression profiling of RIGs arising after cranial irradiation for MB (n=23) and ALL (n=9). Our study reveals a unifying molecular signature for the majority of RIGs, with recurrent PDGFRA amplification and loss of CDKN2A/B and an absence of somatic hotspot mutations in genes encoding histone 3 variants or IDH1/2, uncovering diagnostic markers and potentially actionable targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-27T10:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005244","title":"The_Little_Princess_Knowledge_Bank_RNAseq","description":"The purpose of the knowledge bank is to serve as a community resource and to address the following specific\nquestions about Wilms tumour:\n(1) Do genetic, epigenetic, or transcriptional features predict outcome and thus lend themselves to\ntreatment stratification?\n(2) What are the genetic drivers of Wilms tumour, considering the entire histological spectrum of\nWilms tumour including the most common subtypes classified as intermediate risk?","abstract":"The purpose of the knowledge bank is to serve as a community resource and to address the following specific\nquestions about Wilms tumour:\n(1) Do genetic, epigenetic, or transcriptional features predict outcome and thus lend themselves to\ntreatment stratification?\n(2) What are the genetic drivers of Wilms tumour, considering the entire histological spectrum of\nWilms tumour including the most common subtypes classified as intermediate risk?","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-27T10:57:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005245","title":"Host genetic determinants of HIV infection","description":"Broadly, the objectives of the study are to characterize genetic variation in any gene or genomic region in South African populations, in the first place HIV. The purpose is to apply this knowledge to establish assays and gene signatures to test in disease-association studies, and to study underlying mechanisms of disease causation/severity.","abstract":"Broadly, the objectives of the study are to characterize genetic variation in any gene or genomic region in South African populations, in the first place HIV. The purpose is to apply this knowledge to establish assays and gene signatures to test in disease-association studies, and to study underlying mechanisms of disease causation/severity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-27T13:26:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005246","title":"Distribution of ctDNA levels in plasma of early-stage non-small cell lung cancer patients measured using personalised ctDNA analysis","description":null,"abstract":"Applying custom capture panels to plasma samples from early stage NSCLC patients to detect ctDNA.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005247","title":"Differentiation_systems_profiling","description":"BSseq libraries of timepoints in an in vitro differentiation experiment.","abstract":"This study aims to characterise the epigenome during in vitro differentiation.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005248","title":"Genomic characterization of retinoblastoma","description":null,"abstract":"We studied primary retinoblastoma by Whole-Exome Sequencing.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-27T19:05:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005249","title":"HSC_differentiation","description":"Differentiating haematopoietic stem cells (HSCs) from iPSCs using small molecules and transcription factors. Single cell RNA sequencing of cells during the process to select the optimal combination of TFs.","abstract":"Human haematopoietic stem cells (HSCs) have many therapeutic and research potentials. However, the current use is limited by the availability and scarcity in human bone marrow. One route around the problem is to develop off-the-shelf HSCs from human iPSCs. We aim to select a number of transcription factors that are important in in vivo HSC development, and screen different combinations of these TFs in in vitro HSC generation.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005250","title":"The genomic landscape of pediatric acute lymphoblastic leukemia","description":"Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer and arises from B- or T-lineage lymphocyte precursors. ALL comprises dozens of subtypes, and genomic analyses have largely been performed within these subtypes. Here we analyze pediatric ALL genomes across all subtypes, including 768 whole genomes, 1,729 exomes, and 1,889 transcriptomes in 2,754 patients. Most ALL subtypes harbor 4 or more driver alterations per sample, similar to adult cancers, despite low mutation burdens. Hyperdiploid B-ALL copy gains are likely acquired early and synchronously, with copy gains occurring before ultraviolet-induced mutations. By contrast, ultraviolet-induced mutations precede copy gains in iAMP21 B-ALL. Overall, we identified 378 putative ALL driver genes. Most driver alterations vary in prevalence across ALL subtypes, with B-ALL enriched for Ras and B-lineage-related alterations, and T-ALL enriched for PI3K, JAK, and cell cycle alterations. Most B-ALL (54.3%) and T-ALL (51.2%) samples bear at least one rare driver gene alteration (present in less than 2% of samples), including 30 putative novel cancer driver genes associated with ubiquitination, SUMOylation, non-coding, and other functions. Known or novel alterations associated with poor outcomes in specific subtypes include TBL1XR1 alterations in ETV6-RUNX1 patients, CREBBP in Ph-like-CRLF2, SETD2 in hyperdiploid, and PTEN in TAL1 patients. Intriguingly, DUX4 and KMT2A subtypes separate into CEBPA/FLT3- or NFATC4-expressing subgroups with potential clinical implications. Together, these results deepen understanding of ALL etiology and outcomes, and facilitate ALL model development.","abstract":"Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer and arises from B- or T-lineage lymphocyte precursors. ALL comprises dozens of subtypes, and genomic analyses have largely been performed within these subtypes. Here we analyze pediatric ALL genomes across all subtypes, including 768 whole genomes, 1,729 exomes, and 1,889 transcriptomes in 2,754 patients. Most ALL subtypes harbor 4 or more driver alterations per sample, similar to adult cancers, despite low mutation burdens. Hyperdiploid B-ALL copy gains are likely acquired early and synchronously, with copy gains occurring before ultraviolet-induced mutations. By contrast, ultraviolet-induced mutations precede copy gains in iAMP21 B-ALL. Overall, we identified 378 putative ALL driver genes. Most driver alterations vary in prevalence across ALL subtypes, with B-ALL enriched for Ras and B-lineage-related alterations, and T-ALL enriched for PI3K, JAK, and cell cycle alterations. Most B-ALL (54.3%) and T-ALL (51.2%) samples bear at least one rare driver gene alteration (present in less than 2% of samples), including 30 putative novel cancer driver genes associated with ubiquitination, SUMOylation, non-coding, and other functions. Known or novel alterations associated with poor outcomes in specific subtypes include TBL1XR1 alterations in ETV6-RUNX1 patients, CREBBP in Ph-like-CRLF2, SETD2 in hyperdiploid, and PTEN in TAL1 patients. Intriguingly, DUX4 and KMT2A subtypes separate into CEBPA/FLT3- or NFATC4-expressing subgroups with potential clinical implications. Together, these results deepen understanding of ALL etiology and outcomes, and facilitate ALL model development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-04-29T17:15:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005251","title":"single cell RNAseq characterization of primary ex vivo cultures from HNSCC tumors","description":null,"abstract":"Despite aggressive multi-modal treatment, advanced head and neck squamous cell carcinoma (HNSCC) patients are at high risk of recurrence. Matched pairs (n=38) of primary/recurrent tumors were subjected to whole exome and RNA sequencing. Mutational landscapes and genomic copy number alterations indicated diverging clonal origins in a subset of cases. Transcriptional subtyping (classical/CL, basal/BA, inflamed-mesenchymal/IMS) in primary and recurrent HNSCC (n=112) revealed more frequent CL and IMS in primary tumors with low recurrence rates and a prevalence of BA in recurrent tumors associated with p-EMT and early recurrence. 44% of matched cases underwent a subtype change from primary to recurrent tumors, preferably from IMS to BA or CL. In recurrences, HYPOXIA, P-EMT and RADIATION RESISTANCE signatures were up- and TUMOR INFLAMMATION down-regulated compared to index tumors. A therapy-induced selection of transcriptional subtypes demonstrates the importance of molecular characterization of recurrences for second-line therapy decisions to enable optimally tailored treatments.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005252","title":"SIN3B_role_in_melanoma_resistance_and_progression","description":"Perform whole exome sequencing comparing SIN3B knockout versus control melanoma cells (in three different melanoma cell lines) aiming to identify which genes could be modulated upon SIN3B deletion and look at differences on pathways.","abstract":"Cutaneous melanoma accounts for the majority of skin cancer deaths, owing to its aggressiveness and resistance to targeted therapies, primarily due to the presence of phenotypic and genetic heterogeneity. Thus, there is a dire need to identify new biomarkers of therapy resistance in melanoma, which can aid the development of new therapeutic strategies. SIN3B scaffolding protein has been shown to have an implication in cancer progression. However, the mechanisms underlying SIN3B role in melanoma is currently unknown. Therefore, this study aims to characterize SIN3B molecular function and regulation during melanoma progression and therapy resistance.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005253","title":"Combining a Universal Telomerase Based Cancer Vaccine with Ipilimumab in Patients with Metastatic Melanoma - Five-year Follow up of a Phase I/IIa Trial","description":"Background \nIpilimumab improves survival for patients with metastatic malignant melanoma. Combining a therapeutic cancer vaccine with ipilimumab may increase efficacy by providing enhanced anti-tumor immune responses. UV1 consists of three synthetic long peptides from human telomerase reverse transcriptase (hTERT). These peptides comprise epitopes recognized by T cells from cancer patients experiencing long-term survival following treatment with a first-generation hTERT vaccine, and generate long-lasting immune responses in cancer patients when used as monotherapy. The objective of this trial was to investigate the safety and efficacy of combining UV1 with ipilimumab in metastatic melanoma. \nPatients and methods\nIn this phase I/IIa, single center trial [NCT02275416], patients with metastatic melanoma received repeated UV1 vaccinations, with GM-CSF as an adjuvant, in combination with ipilimumab. Patients were evaluated for safety, efficacy and immune response. Immune responses against vaccine peptides were monitored in peripheral blood by measuring antigen-specific proliferation and IFN-γ production. \nResults\nTwelve patients were recruited. Adverse events were mainly diarrhea, injection site reaction, pruritus, rash, nausea and fatigue. Ten patients showed a Th1 immune response to UV1 peptides, occurring early and after few vaccinations. Three patients obtained a partial response and one patient a complete response. Overall survival was 50% at 5 years. \nConclusion\nTreatment was well tolerated. The rapid expansion of UV1-specific Th1 cells in the majority of patients indicates synergy between UV1 vaccine and CTLA-4 blockade.  This may have translated into clinical benefit, encouraging the combination of UV1 vaccination with standard of care treatment regimes containing ipilimumab/CTLA-4 blocking antibodies.","abstract":"Background \nIpilimumab improves survival for patients with metastatic malignant melanoma. Combining a therapeutic cancer vaccine with ipilimumab may increase efficacy by providing enhanced anti-tumor immune responses. UV1 consists of three synthetic long peptides from human telomerase reverse transcriptase (hTERT). These peptides comprise epitopes recognized by T cells from cancer patients experiencing long-term survival following treatment with a first-generation hTERT vaccine, and generate long-lasting immune responses in cancer patients when used as monotherapy. The objective of this trial was to investigate the safety and efficacy of combining UV1 with ipilimumab in metastatic melanoma. \nPatients and methods\nIn this phase I/IIa, single center trial [NCT02275416], patients with metastatic melanoma received repeated UV1 vaccinations, with GM-CSF as an adjuvant, in combination with ipilimumab. Patients were evaluated for safety, efficacy and immune response. Immune responses against vaccine peptides were monitored in peripheral blood by measuring antigen-specific proliferation and IFN-γ production. \nResults\nTwelve patients were recruited. Adverse events were mainly diarrhea, injection site reaction, pruritus, rash, nausea and fatigue. Ten patients showed a Th1 immune response to UV1 peptides, occurring early and after few vaccinations. Three patients obtained a partial response and one patient a complete response. Overall survival was 50% at 5 years. \nConclusion\nTreatment was well tolerated. The rapid expansion of UV1-specific Th1 cells in the majority of patients indicates synergy between UV1 vaccine and CTLA-4 blockade.  This may have translated into clinical benefit, encouraging the combination of UV1 vaccination with standard of care treatment regimes containing ipilimumab/CTLA-4 blocking antibodies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-03T07:19:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005254","title":"Identification and functional characterisation of a rare MTTP variant underlying familial non-alcoholic fatty liver disease","description":"We identified a rare causal variant in MTTP, c.1691T&gt;C p.I564T (rs745447480) encoding microsomal triglyceride transfer protein (MTP) causing progressive non-alcoholic fatty liver disease with cirrhosis and hepatocellular carcinoma unrelated to metabolic syndrome, without manifestations of abetalipoproteinemia, in a four generation family with South Asian ancestry. Variant-expressing hepatocyte-like-cells (HLCs) derived from human induced pluripotent stem cells generated from homozygous donor skin fibroblasts had lower lipoprotein ApoB secretion, compared to wild type cells. Cytoplasmic triglyceride accumulation in HLCs triggered endoplasmic reticulum stress, secretion of pro-inflammatory mediators, production of reactive oxygen species, delineating the progression of disease associated with homozygosity for MTTP p.I564T","abstract":"We identified a rare causal variant in MTTP, c.1691T&gt;C p.I564T (rs745447480) encoding microsomal triglyceride transfer protein (MTP) causing progressive non-alcoholic fatty liver disease with cirrhosis and hepatocellular carcinoma unrelated to metabolic syndrome, without manifestations of abetalipoproteinemia, in a four generation family with South Asian ancestry. Variant-expressing hepatocyte-like-cells (HLCs) derived from human induced pluripotent stem cells generated from homozygous donor skin fibroblasts had lower lipoprotein ApoB secretion, compared to wild type cells. Cytoplasmic triglyceride accumulation in HLCs triggered endoplasmic reticulum stress, secretion of pro-inflammatory mediators, production of reactive oxygen species, delineating the progression of disease associated with homozygosity for MTTP p.I564T","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-03T10:06:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005255","title":"Comparison of capture-based method for transcriptome profiling of formalin-fixed paraffin embedded tumor samples","description":"Background: The need for fresh frozen (FF) tissue limits implementing RNA sequencing (RNA-seq) in the clinic. The majority of clinical samples are stored as formalin-fixed, paraffin-embedded (FFPE) tissues. Exome capture platforms have been developed for RNA-seq from FFPE samples. However, these methods have not been systematically compared.\nMethods: Transcriptomic analysis of 32 FFPE tumor samples from 11 patients was performed using three exome capture-based methods: Agilent SureSelect V6, TWIST NGS Exome, and IDT XGen Exome Research Panel. We compared these methods to TruSeq RNA-seq of fresh frozen (FF-TruSeq) tumor samples from the same patients. We assessed the recovery of clinically relevant biological features. \nResults: The Spearman's correlation coefficients between the global expression profiles of the three capture-based methods from FFPE and matched FF-TruSeq were high (rho = 0.72-0.9, p &lt; 0.05). A significant correlation between the expression of key immune genes between individual capture-based methods and FF-TruSeq (rho = 0.76-0.88, p &lt; 0.05) was observed. All exome capture-based methods reliably detected outlier expression of actionable genes, including ERBB2, MET, NTRK1, and PPARG. In urothelial cancer samples, the Agilent assay was associated with the highest molecular subtype concordance with FF-TruSeq (Cohen's k = 0.7, p &lt; 0.01). Both Agilent and IDT detected all the clinically relevant fusions that were initially identified in FF-TruSeq. \nConclusion: All exome capture-based methods had comparable performance and concordance with FF-TruSeq. By enabling the interrogation of FFPE tumor samples, our findings will enable the implementation of RNA-seq in the clinic to guide precision oncology approaches.","abstract":"Background: The need for fresh frozen (FF) tissue limits implementing RNA sequencing (RNA-seq) in the clinic. The majority of clinical samples are stored as formalin-fixed, paraffin-embedded (FFPE) tissues. Exome capture platforms have been developed for RNA-seq from FFPE samples. However, these methods have not been systematically compared.\nMethods: Transcriptomic analysis of 32 FFPE tumor samples from 11 patients was performed using three exome capture-based methods: Agilent SureSelect V6, TWIST NGS Exome, and IDT XGen Exome Research Panel. We compared these methods to TruSeq RNA-seq of fresh frozen (FF-TruSeq) tumor samples from the same patients. We assessed the recovery of clinically relevant biological features. \nResults: The Spearman's correlation coefficients between the global expression profiles of the three capture-based methods from FFPE and matched FF-TruSeq were high (rho = 0.72-0.9, p &lt; 0.05). A significant correlation between the expression of key immune genes between individual capture-based methods and FF-TruSeq (rho = 0.76-0.88, p &lt; 0.05) was observed. All exome capture-based methods reliably detected outlier expression of actionable genes, including ERBB2, MET, NTRK1, and PPARG. In urothelial cancer samples, the Agilent assay was associated with the highest molecular subtype concordance with FF-TruSeq (Cohen's k = 0.7, p &lt; 0.01). Both Agilent and IDT detected all the clinically relevant fusions that were initially identified in FF-TruSeq. \nConclusion: All exome capture-based methods had comparable performance and concordance with FF-TruSeq. By enabling the interrogation of FFPE tumor samples, our findings will enable the implementation of RNA-seq in the clinic to guide precision oncology approaches.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-03T14:55:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005256","title":"Whole genome sequencing of adult glioblastoma nuclei","description":"Nuclei were extracted from three primary adult glioblastoma samples and processed for scATAC-seq, and residual nuclei left over from these same samples were used to extract DNA and processed and sequenced for WGS. This WGS data was then used to cross-validate assessment of large-scale copy number alterations with scATAC-seq using the Copy-scAT tool.","abstract":"Nuclei were extracted from three primary adult glioblastoma samples and processed for scATAC-seq, and residual nuclei left over from these same samples were used to extract DNA and processed and sequenced for WGS. This WGS data was then used to cross-validate assessment of large-scale copy number alterations with scATAC-seq using the Copy-scAT tool.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-03T15:21:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005257","title":"Single-cell RNA sequencing of 6 follicular lymphoma tumors","description":"Follicular lymphoma (FL) is an indolent cancer of mature B-cells but carries increased risk of transformation to a more aggressive histology over time. We present here comprehensive profiling both tumor and immune compartments in 6 diagnostic FL biopsies by single-cell RNA sequencing. This confirmed results from 155 FL tumors characterized by mass cytometry (CyTOF) which revealed two distinct evolutionary trajectories with disparate risk of transformation and alternate biologies.","abstract":"Follicular lymphoma (FL) is an indolent cancer of mature B-cells but carries increased risk of transformation to a more aggressive histology over time. We present here comprehensive profiling both tumor and immune compartments in 6 diagnostic FL biopsies by single-cell RNA sequencing. This confirmed results from 155 FL tumors characterized by mass cytometry (CyTOF) which revealed two distinct evolutionary trajectories with disparate risk of transformation and alternate biologies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-04T03:00:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005258","title":"CD27hiCD38hi plasmablasts are activated B cells of mixed origin with distinct function","description":null,"abstract":"Clinically important broadly reactive B cells evolve during multiple infections. The phenotype and function of B cells re-activated after secondary infection is different compared to B cells activated after a primary infection. Here we studied CD27highCD38high plasmablasts from patients with a primary or secondary dengue virus infection. Three transcriptionally and functionally distinct plasmablast clusters were identified. The largest cluster 0/1 was plasma cell-related and contained cells coding for virus serotype cross-reactive antibodies of the IgG1 isotype, consistent with memory B cell activation during an extrafollicular response. In contrast, cells in clusters 2 and 3 expressed low levels of antibody genes and high levels of genes associated with oxidative phosphorylation, EIF2 pathway and mitochondrial dysfunction. Clusters 2 and 3, which we name T cell-dependent plasmablasts, showed a transcriptional footprint of T cell help, in line with activation from either naïve B cells or memory B cells. Our results contribute to the understanding of the parallel B cell activation events that occur in humans after natural primary and secondary infection.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-04T06:47:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005259","title":"Single-cell chromatin accessibility landscape identifies tissue repair program in human regulatory T cells part 2","description":"Studies over the past decade characterized murine regulatory T cells (Tregs) with the capacity to promote tissue regeneration. In humans, such a population of tissue-repair Treg cells has not been discovered yet. Using single-cell chromatin accessibility profiles of murine and human tissue Treg cells, we defined a species-conserved and microbiota-independent repair Treg signature, with a prevailing footprint of the transcription factor BATF. Combining this signature with gene expression profiling and TCR fate mapping, we identified a population of tissue-like Treg cells in peripheral blood, characterized by the expression of BATF, CCR8 and HLA-DR. Human BATF+CCR8+ Treg cells from normal skin and adipose tissue shared features with tumor-resident Treg and tissue T-follicular helper (Tfh) cells. Inducing a Tfh-like differentiation program in naive Treg cells partially recapitulated human tissue Treg characteristics, including enhanced wound healing potential","abstract":"Studies over the past decade characterized murine regulatory T cells (Tregs) with the capacity to promote tissue regeneration. In humans, such a population of tissue-repair Treg cells has not been discovered yet. Using single-cell chromatin accessibility profiles of murine and human tissue Treg cells, we defined a species-conserved and microbiota-independent repair Treg signature, with a prevailing footprint of the transcription factor BATF. Combining this signature with gene expression profiling and TCR fate mapping, we identified a population of tissue-like Treg cells in peripheral blood, characterized by the expression of BATF, CCR8 and HLA-DR. Human BATF+CCR8+ Treg cells from normal skin and adipose tissue shared features with tumor-resident Treg and tissue T-follicular helper (Tfh) cells. Inducing a Tfh-like differentiation program in naive Treg cells partially recapitulated human tissue Treg characteristics, including enhanced wound healing potential","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005260","title":"Characterizing microbiome-directed fibre snacks in gnotobiotic mice and humans","description":null,"abstract":"Knowledge of the interrelationships between what we eat and the configurations of our gut microbial communities is providing important insights into how food components that are not directly metabolized by human enzymes are linked to our physiology and health status. Changing food preferences brought about by Westernization that have deleterious health effects1,2, plus rapid population expansion, ongoing challenges to sustainable agriculture, and other forces contributing to increased food insecurity, are catalyzing efforts to identify more nutritious and affordable foods3. The gut microbial community is complex, dynamic, and exhibits considerable intra- and interpersonal variation in its composition and functions. The massive number of potential interactions between its components makes it challenging to define the mechanisms by which food ingredients affect community properties. There is also a paucity of information about the ‘bioactive’ ingredients of foods that influence the fitness and expressed functions of community members. Here, plant fibres, from different sustainable sources and targeting distinct features of obese human gut microbiomes in gnotobiotic mice, were formulated into snack prototypes and used to supplement controlled diets consumed by overweight and obese adults; the results revealed fibre-specific changes in their microbiomes that were linked to changes in their plasma proteomes indicative of altered physiologic state.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005261","title":"REST transcription factor binding in glioma patients","description":null,"abstract":"REST binding is believed to be affected by epigenomic mechanisms and also is known to shape epigenomic environment. We have studied REST binding in the context of well-described epigenomic alteration caused by single nucleotide mutations in IDH1 or IDH2 genes, causing the so-called IDH-phenotype in glioma samples. To select genes under REST regulation, we have used siRNA technology to silence the REST dependant genes. Additionally, we have used global chromatin immunoprecipitation profiles of REST on two isogenic IDH WT/mutant glioblastoma cell line subtypes, to define IDH-phenotype specific REST binding sites. Results obtained from glioblastoma cell lines were verified in tumor samples from The Cancer Genome Atlas repository and on our own cohort of tumor samples We have found that IDH mutant and WT cells differ in terms of REST-regulated genes and pathways. Difference in regulation of REST targets in IDH-mutant/WT cells may come from different transcription factor motifs composition of IDH-mutant or IDH-WT specific REST binding sites. On the functional level we have found that REST controls a group of genes associated with the shift between migration and cell differentiation and its effect is different, depending on IDH-phenotype. In the summary, REST may acquire or lose specific functions depending on epigenomic changes dependent from IDH-phenotype.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005262","title":"Deconvolution of sarcoma methylomes reveals varying degrees of immune cell infiltrates with association to genomic aberrations","description":"Soft-tissue sarcomas (STS) are a heterogeneous group of mesenchymal tumors for which response to immunotherapies is not well established. Therefore, it is important to risk-stratify and identify STS patients who will most likely benefit from these treatments.To reveal shared and distinct methylation signatures present in STS, we performed unsupervised deconvolution of DNA methylation data from the TCGA sarcoma and an independent validation cohort. We showed that leiomyosarcoma can be subclassified into three distinct methylation groups. More importantly, we identified a component associated with tumor-infiltrating leukocytes, which suggests varying degrees of immune cell infiltration in STS subtypes and an association with prognosis. We further investigated the genomic alterations that may influence tumor infiltration by leukocytes including RB1 loss in undifferentiated pleomorphic sarcomas and ELK3 amplification in dedifferentiated liposarcomas. In summary, we have leveraged unsupervised methylation-based deconvolution to characterize the immune compartment and molecularly stratify subtypes in STS, which may benefit precision medicine in the future.","abstract":"Soft-tissue sarcomas (STS) are a heterogeneous group of mesenchymal tumors for which response to immunotherapies is not well established. Therefore, it is important to risk-stratify and identify STS patients who will most likely benefit from these treatments.To reveal shared and distinct methylation signatures present in STS, we performed unsupervised deconvolution of DNA methylation data from the TCGA sarcoma and an independent validation cohort. We showed that leiomyosarcoma can be subclassified into three distinct methylation groups. More importantly, we identified a component associated with tumor-infiltrating leukocytes, which suggests varying degrees of immune cell infiltration in STS subtypes and an association with prognosis. We further investigated the genomic alterations that may influence tumor infiltration by leukocytes including RB1 loss in undifferentiated pleomorphic sarcomas and ELK3 amplification in dedifferentiated liposarcomas. In summary, we have leveraged unsupervised methylation-based deconvolution to characterize the immune compartment and molecularly stratify subtypes in STS, which may benefit precision medicine in the future.","study_type":"Other","pubmed_ids":[33980253],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005263","title":"The Extracellular RNA Quality Control (exRNAQC) study (phase 1)","description":null,"abstract":"The use of blood-based extracellular RNA (exRNA) as clinical biomarker requires the implementation of a validated procedure for sample collection, processing and profiling. So far, no study has systematically addressed the pre-analytical variables affecting transcriptome analysis of exRNAs. In the exRNAQC study, we evaluated 10 blood collection tubes, 3 time points between blood draw and downstream processing, and 8 RNA purification methods using the supplier-specified minimum and maximum biofluid input volumes. The impact of these pre-analytics is assessed by deep transcriptome profiling of both small and messenger RNA from healthy donors' plasma or serum. Experiments are conducted in triplicate (for a total of 276 transcriptomes) using 189 synthetic spike-in RNAs as processing controls. When comparing blood tubes, so-called blood preservation tubes do not stabilize RNA very well, as is reflected by increasing RNA concentration and number of detected genes over time, and by compromised reproducibility. We also document large differences in RNA purification kit performance in terms of sensitivity, reproducibility, and observed transcriptome complexity. Our results are summarized in 11 performance metrics that enable an informed selection of the most optimal sample processing workflow for your own experiments. In conclusion, we put forward robust quality control metrics for exRNA quantification methods with validated standard operating procedures (SOPs) for processing, representing paramount groundwork for future exRNA-based precision medicine applications.\n\nMore project info on bioRxiv (manuscript title: Performance of RNA purification kits and blood collection tubes in the Extracellular RNA Quality Control (exRNAQC) study) and https://oncornalab.ugent.be/project/exrnaqc/","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-05T10:13:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005264","title":"Whole genome sequencing of EBV Associated Nasopharyngeal Carcinoma","description":null,"abstract":"testest","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005265","title":"Part_A__pilot___Deep_dive_for_eQTLs_in_inflammatory_bowel_disease_relevant_cell_types","description":"Pilot study to flow sort cells from endocopic gut biopsies for bulk RNAseq using NEB single cell RNA seq kit","abstract":"We are currently building single cell eQTL maps for IBD relevant cell types using 10X scRNA-seq. This unbiased approach will identify the major cell types driving IBD, but a limitation is that 10X will only capture intergenic eQTLs, less abundant transcripts will fall below the detection threshold and certain cell types e.g. neutrophils and fibroblasts, are either underrepresented or missing. Here, we flow-sort two disease-relevant cell types (Treg and inflammatory macrophages) from single cell suspensions of gut biopsies for bulk RNA seq from low number of cells to build more comprehensive eQTL maps, including intronic splice QTLS, from which to identify candidate drug targets.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005266","title":"a testing test","description":null,"abstract":"testing tests for testing purposes","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005267","title":"Aneuploidy_and_human_development","description":"We will investigate the transcriptomic consequences of copy number changes in human development.","abstract":"Every normal human cell has two copies of each non-sex chromosome.  The gain or loss of an extra copy underlies many health conditions, including developmental syndromes and cancer.  Ultimately, it is the patterns of genes that are turned on and off that determines which proteins a cell produces and its biological function.  Despite the importance of changes in chromosome number (known as aneuploidy or copy number changes), little is known about how these changes impact patterns of gene expression.  This project will aim to fill this gap by creating an atlas of patterns of gene expression in cells from developmental tissues with aberrant numbers of chromosomes.  These gene expression profiles will then be compared to the patterns of expression in the same cells with two copies of each chromosome, directly measuring the precise, cell specific, consequences of copy number change on gene expression.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-05T12:57:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005268","title":"Characterizing microbiome-directed fibre snacks in gnotobiotic mice and humans","description":"Knowledge of the interrelationships between what we eat and the configurations of our gut microbial communities is providing important insights into how food components that are not directly metabolized by human enzymes are linked to our physiology and health status. Changing food preferences brought about by Westernization that have deleterious health effects1,2, plus rapid population expansion, ongoing challenges to sustainable agriculture, and other forces contributing to increased food insecurity, are catalyzing efforts to identify more nutritious and affordable foods3. The gut microbial community is complex, dynamic, and exhibits considerable intra- and interpersonal variation in its composition and functions. The massive number of potential interactions between its components makes it challenging to define the mechanisms by which food ingredients affect community properties. There is also a paucity of information about the ‘bioactive’ ingredients of foods that influence the fitness and expressed functions of community members. Here, plant fibres, from different sustainable sources and targeting distinct features of obese human gut microbiomes in gnotobiotic mice, were formulated into snack prototypes and used to supplement controlled diets consumed by overweight and obese adults; the results revealed fibre-specific changes in their microbiomes that were linked to changes in their plasma proteomes indicative of altered physiologic state.","abstract":"Knowledge of the interrelationships between what we eat and the configurations of our gut microbial communities is providing important insights into how food components that are not directly metabolized by human enzymes are linked to our physiology and health status. Changing food preferences brought about by Westernization that have deleterious health effects1,2, plus rapid population expansion, ongoing challenges to sustainable agriculture, and other forces contributing to increased food insecurity, are catalyzing efforts to identify more nutritious and affordable foods3. The gut microbial community is complex, dynamic, and exhibits considerable intra- and interpersonal variation in its composition and functions. The massive number of potential interactions between its components makes it challenging to define the mechanisms by which food ingredients affect community properties. There is also a paucity of information about the ‘bioactive’ ingredients of foods that influence the fitness and expressed functions of community members. Here, plant fibres, from different sustainable sources and targeting distinct features of obese human gut microbiomes in gnotobiotic mice, were formulated into snack prototypes and used to supplement controlled diets consumed by overweight and obese adults; the results revealed fibre-specific changes in their microbiomes that were linked to changes in their plasma proteomes indicative of altered physiologic state.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-05T20:22:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005269","title":"Recurrent_ependymoma_DNA_WGS","description":"Examining the genomics of recurrent ependymomas using whole genome sequencing.","abstract":"A subset of ependymomas recur, potentially several times, after surgical resection. Using whole genome sequencing, we wish to establish if the recurrence arises from the original tumour or if there is a 'field cancerisation' effect in the surrounding ependyma in which new tumours may occur. This study also seeks to understand whether they are driven by particular variants, perhaps distinct from those that do not recur.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005270","title":"Molecular characteristics in Burkitt lymphoma over age groups","description":"Treatment optimization has improved the overall survival in Burkitt lymphoma (BL) patients but there are still relevant outcome differences between pediatric and adult patients. In both age groups survival remains poor for patients who suffer relapse. Therefore, new treatment approaches are warranted to improve survival. Thus, we conducted a comparative study in the largest pediatric cohort to date including 191 cases and 97 samples from adult patients and analyzed the mutational landscape. We detected overlapping molecular profiles but also significant differences in the mutational pattern. Samples from pediatric patients show a higher frequency of mutations in ID3, DDX3X and BAF-complex components ARID1A and SMARCA4, while YY1AP1 and BCL2 are more frequently mutated in cases from adult BL patients. Correlation of the mutational profile with clinical data was available for the pediatric cohort and identified TP53 mutations to be highly significantly associated with the incidence of relapse thus identifying the first molecular marker to be associated with the incidence of relapse in pediatric BL. As the hotspot analysis of TP53 mutations showed mostly gain of function mutations, it is tempting to speculate that drugs decreasing the amount of malignant TP53 or increase the abundance of wildtype TP53 could be a promising approach for future treatment regimens to further improve prognosis.","abstract":"Treatment optimization has improved the overall survival in Burkitt lymphoma (BL) patients but there are still relevant outcome differences between pediatric and adult patients. In both age groups survival remains poor for patients who suffer relapse. Therefore, new treatment approaches are warranted to improve survival. Thus, we conducted a comparative study in the largest pediatric cohort to date including 191 cases and 97 samples from adult patients and analyzed the mutational landscape. We detected overlapping molecular profiles but also significant differences in the mutational pattern. Samples from pediatric patients show a higher frequency of mutations in ID3, DDX3X and BAF-complex components ARID1A and SMARCA4, while YY1AP1 and BCL2 are more frequently mutated in cases from adult BL patients. Correlation of the mutational profile with clinical data was available for the pediatric cohort and identified TP53 mutations to be highly significantly associated with the incidence of relapse thus identifying the first molecular marker to be associated with the incidence of relapse in pediatric BL. As the hotspot analysis of TP53 mutations showed mostly gain of function mutations, it is tempting to speculate that drugs decreasing the amount of malignant TP53 or increase the abundance of wildtype TP53 could be a promising approach for future treatment regimens to further improve prognosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-06T12:36:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005271","title":"Human Inflammatory Skin Disease scRNA-seq","description":null,"abstract":"scRNA-seq of inflammatory skin diseases","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-06T18:09:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005272","title":"ProjectMinE : whole-genome sequence data of ALS patients and controls","description":null,"abstract":"The most recent genome-wide association study in amyotrophic lateral sclerosis (ALS) demonstrates a disproportionate contribution from low-frequency variants to genetic susceptibility to disease. We have therefore begun Project MinE, an international collaboration that seeks to analyze whole-genome sequence data of at least 15 000 ALS patients and 7500 controls.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005273","title":"Exome_sequencing_of_UK_Birth_Cohorts___Avon_Longitudinal_Study_of_Parents_and_Children","description":"We propose to exome sequence birth cohorts with near complete population coverage (thus addressing the ascertainment biases of previous studies), which have detailed longitudinal cognitive and educational data on parents and children, and for which genotyping chip data are readily available.","abstract":"Birth cohort studies involve repeated surveys of large numbers of individuals from birth and throughout their lives. They collect information useful for a wide range of life course research domains, and biological samples which can be used to derive data from an increasing collection of omic technologies. This rich source of longitudinal data, when combined with genomic data, offers the scientific community valuable insights from population genetics to rare disease associations.\n\nAvon Longitudinal Study of Parents and Children (ALSPAC)recruited 14,775 babies of predominantly White ethnicity in the Avon county of south-west England between 1991 and 1992. Born in Bradford (BiB) is similarly focused on a particular local area, the city of Bradford in the north of England, and recruited 13,858 babies between 2007 and 2011, of whom ~41% self-report as white British and ~59% as other ethnicities, predominantly Pakistani. Millennium Cohort Study (MCS) is a national cohort that recruited 18,827 children born between 2000 and 2002, intentionally over-sampling areas with high child poverty, large ethnic minority populations, and smaller UK nations (Wales, Scotland and Northern Ireland)\n\n \n\nAvailable here is a subset of exome-sequenced parents and children from these studies (CRAMS and post-QC VCFs) as detailed in this data note.\n\n \n\nPhenotypic data is also available  by submitting an application to the corresponding cohort:\n\nhttps://www.bristol.ac.uk/alspac/researchers/our-data/ [bristol.ac.uk]","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-07T10:17:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005274","title":"Prediction of HLA genotypes using NGS data","description":"High-precision human leukocyte antigen (HLA) genotyping is crucial for anti-cancer immunotherapy, but existing tools predicting HLA genotypes using next-generation sequencing (NGS) data are insufficiently accurate.","abstract":"High-precision human leukocyte antigen (HLA) genotyping is crucial for anti-cancer immunotherapy, but existing tools predicting HLA genotypes using next-generation sequencing (NGS) data are insufficiently accurate.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-07T10:53:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005276","title":"Genomic and Transcriptomic Profile of Paired Primary-Metastasis Colorectal Tumors","description":"The goal of this study is to identify mechanisms of metastization in a portuguese cohort of colorectal cancer. Namely, we want to identify patterns of genomic and transcriptomic diversification associated with metastasis.","abstract":"The goal of this study is to identify mechanisms of metastization in a portuguese cohort of colorectal cancer. Namely, we want to identify patterns of genomic and transcriptomic diversification associated with metastasis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-07T17:12:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005277","title":"Extracellular transcriptome in seminal plasma for non-invasive prostate cancer diagnosis","description":"A diagnostic non-invasive biomarker test for prostate cancer at an early stage, with high sensitivity and specificity, would improve diagnostic decision making. Extracellular RNAs present in seminal plasma might contain biomarker potential for the accurate detection of clinically significant prostate cancer. So far, the extracellular messenger RNA (mRNA) profile of seminal plasma has not been interrogated for its biomarker potential in the context of prostate cancer. Here, we investigate the mRNA transcriptome in seminal plasma samples obtained from prostate cancer patients (n=25), patients with benign prostate hyperplasia (n=26) and individuals without prostatic disease (n=6). Seminal plasma harbors a complex mRNA repertoire that reflects prostate as its tissue of origin. The endogenous RNA content is higher in the prostate cancer samples compared to the control samples. Prostate cancer antigen 3 (PCA3), a long non-coding RNA with prostate cancer-specific overexpression, and ATP-binding cassette transporter 1 (ABCA1), known to be involved in the prostate cancer pathogenesis, were more abundant in the prostate cancer group. In addition, twelve high confidence fusion transcripts could be detected in prostate cancer samples, including the bona-fide prostate cancer fusion transcript TMPRSS2-ERG. Our findings provide proof-of-principle that the extracellular transcriptome of seminal plasma can reveal information of an underlying prostate cancer.","abstract":"A diagnostic non-invasive biomarker test for prostate cancer at an early stage, with high sensitivity and specificity, would improve diagnostic decision making. Extracellular RNAs present in seminal plasma might contain biomarker potential for the accurate detection of clinically significant prostate cancer. So far, the extracellular messenger RNA (mRNA) profile of seminal plasma has not been interrogated for its biomarker potential in the context of prostate cancer. Here, we investigate the mRNA transcriptome in seminal plasma samples obtained from prostate cancer patients (n=25), patients with benign prostate hyperplasia (n=26) and individuals without prostatic disease (n=6). Seminal plasma harbors a complex mRNA repertoire that reflects prostate as its tissue of origin. The endogenous RNA content is higher in the prostate cancer samples compared to the control samples. Prostate cancer antigen 3 (PCA3), a long non-coding RNA with prostate cancer-specific overexpression, and ATP-binding cassette transporter 1 (ABCA1), known to be involved in the prostate cancer pathogenesis, were more abundant in the prostate cancer group. In addition, twelve high confidence fusion transcripts could be detected in prostate cancer samples, including the bona-fide prostate cancer fusion transcript TMPRSS2-ERG. Our findings provide proof-of-principle that the extracellular transcriptome of seminal plasma can reveal information of an underlying prostate cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-10T09:59:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005278","title":"HCA_Skin_Disease_WSSS_Spatial_NCL","description":"Defining the spatial transcriptome and cell-cell interactions in eczema and psoriasis skin","abstract":"This research aims to dissect the mechanisms driving inflammatory skin diseases using spatial genomics methods in order to improve diagnosis, molecular classification and guide treatment strategies. Spatial genomics profiling using the 10x Visium platform will allow us to simultaneously visualise cells in their microenvironment as well as their gene expression signatures, further understanding their role and behaviour in situ. These data will also be integrated with the previously-generated single-cell skin atlas, conducted as part of the Human Cell Atlas Initiative, to map all the cells in the human body.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-10T10:47:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005279","title":"Loss of SDHB promotes dysregulated iron homeostasis, oxidative stress and sensitivity to ascorbate","description":"Succinate dehydrogenase is a key enzyme in the tricarboxylic acid cycle and the electron transport chain. All four subunits of succinate dehydrogenase are tumor suppressor genes predisposing to paraganglioma, but only mutations in the SDHB subunit are associated with increased risk of metastasis. Here we generated an Sdhd knockout chromaffin cell line and compared it to Sdhb-deficient cells. Both cell types exhibited similar SDH loss of function, metabolic adaptation, and succinate accumulation. In contrast, Sdhb-/- cells showed hallmarks of mesenchymal transition associated with increased DNA hypermethylation and a stronger pseudo-hypoxic phenotype compared to Sdhd-/- cells. Loss of SDHB specifically led to increased oxidative stress associated with dysregulated iron and copper homeostasis in the absence of NRF2 activation. High-dose ascorbate exacerbated the increase in mitochondrial reactive oxygen species, leading to cell death in Sdhb-/- cells. These data establish a mechanism linking oxidative stress to iron homeostasis that specifically occurs in SDHB deficient cells and may promote metastasis. They also highlight high-dose ascorbate as a promising therapeutic strategy for SDHB-related cancers.","abstract":"Succinate dehydrogenase is a key enzyme in the tricarboxylic acid cycle and the electron transport chain. All four subunits of succinate dehydrogenase are tumor suppressor genes predisposing to paraganglioma, but only mutations in the SDHB subunit are associated with increased risk of metastasis. Here we generated an Sdhd knockout chromaffin cell line and compared it to Sdhb-deficient cells. Both cell types exhibited similar SDH loss of function, metabolic adaptation, and succinate accumulation. In contrast, Sdhb-/- cells showed hallmarks of mesenchymal transition associated with increased DNA hypermethylation and a stronger pseudo-hypoxic phenotype compared to Sdhd-/- cells. Loss of SDHB specifically led to increased oxidative stress associated with dysregulated iron and copper homeostasis in the absence of NRF2 activation. High-dose ascorbate exacerbated the increase in mitochondrial reactive oxygen species, leading to cell death in Sdhb-/- cells. These data establish a mechanism linking oxidative stress to iron homeostasis that specifically occurs in SDHB deficient cells and may promote metastasis. They also highlight high-dose ascorbate as a promising therapeutic strategy for SDHB-related cancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005280","title":"Impaired Humoral and Cellular Immunity after SARS-CoV2 BNT162b2 (Tozinameran) Prime-Boost Vaccination in Kidney Transplant Recipients","description":null,"abstract":"Novel mRNA-based vaccines have been proven powerful tools to combat the global pandemic caused by SARS-CoV2 with BNT162b2 efficiently protecting individuals from COVID-19 across a broad age range. Still, it remains largely unknown how renal insufficiency and immunosuppressive medication affect development of vaccine induced immunity. We therefore comprehensively analyzed humoral and cellular responses in kidney transplant recipients after prime-boost vaccination with BNT162b2. As opposed to all healthy vaccinees and the majority of hemodialysis patients, only 4/39 and 1/39 transplanted individuals showed IgA and IgG seroconversion at day 8±1 after booster immunization with minor changes until day 23±5, respectively. Although most transplanted patients mounted spike-specific T helper cell responses, frequencies were significantly reduced compared to controls and dialysis patients, accompanied by a broad impairment in effector cytokine production, memory differentiation and activation-related signatures. Spike-specific CD8+ T cell responses were less abundant than their CD4+ counterparts in healthy controls and hemodialysis patients and almost undetectable in transplant patients. Signs of alloreactivity promoted by BNT162b2 were not documented within the observation period. In summary, our data strongly suggest revised vaccination approaches in immunosuppressed patients, including individual immune monitoring for protection of this vulnerable group at risk to develop severe COVID-19.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-10T13:51:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005281","title":"ATAC-seq data in normal colon mucosa","description":"This dataset includes ATAC-seq data generated in normal colon mucosa obtained in four healthy volunteers during colonoscopy indicated for colorectal cancer screening. Subjects had no lesions in the colon. Also includes one frozen sw480 colon adenocarcinoma cell line sample for piloting the protocol","abstract":"This dataset includes ATAC-seq data generated in normal colon mucosa obtained in four healthy volunteers during colonoscopy indicated for colorectal cancer screening. Subjects had no lesions in the colon. Also includes one frozen sw480 colon adenocarcinoma cell line sample for piloting the protocol","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-11T09:16:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005282","title":"Twist_targeted_sequencing___AX001","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005283","title":"Twist_targeted_sequencing___CB001","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005284","title":"Twist_targeted_sequencing___CB002","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005285","title":"Twist_targeted_sequencing___KX001","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005286","title":"Hypoxia acts as an environmental cue for the human TRM differentiation program","description":"Tissue-resident memory T-cells (TRM) provide frontline defense against infectious diseases and contribute to anti-tumor immunity; however, aside from the necessity of TGF-β, knowledge regarding TRM-inductive cues remains incomplete, particularly for human cells. Oxygen tension is an environmental cue that distinguishes peripheral tissues from the circulation and here, we demonstrate that differentiation of human CD8+ T-cells in the presence of hypoxia and TGF-β1 led to the development of a TRM phenotype, characterized by a greater than five-fold increase in CD69+CD103+ cells expressing human TRM hallmarks and enrichment for endogenous human TRM gene signatures, including increased adhesion molecule expression and decreased expression of genes involved in recirculation. Hypoxia and TGF-β1 synergized to produce a significantly larger population of TRM phenotype cells than either condition alone, and comparison of these cells from the individual and combination conditions revealed distinct phenotypic and transcriptional profiles, indicating a programming response to milieu rather than a mere expansion. Our findings identify a previously unreported cue for the TRM differentiation program and can enable facile generation of human TRM phenotype cells in vitro for basic studies and translational applications such as adoptive cellular therapy.","abstract":"Tissue-resident memory T-cells (TRM) provide frontline defense against infectious diseases and contribute to anti-tumor immunity; however, aside from the necessity of TGF-β, knowledge regarding TRM-inductive cues remains incomplete, particularly for human cells. Oxygen tension is an environmental cue that distinguishes peripheral tissues from the circulation and here, we demonstrate that differentiation of human CD8+ T-cells in the presence of hypoxia and TGF-β1 led to the development of a TRM phenotype, characterized by a greater than five-fold increase in CD69+CD103+ cells expressing human TRM hallmarks and enrichment for endogenous human TRM gene signatures, including increased adhesion molecule expression and decreased expression of genes involved in recirculation. Hypoxia and TGF-β1 synergized to produce a significantly larger population of TRM phenotype cells than either condition alone, and comparison of these cells from the individual and combination conditions revealed distinct phenotypic and transcriptional profiles, indicating a programming response to milieu rather than a mere expansion. Our findings identify a previously unreported cue for the TRM differentiation program and can enable facile generation of human TRM phenotype cells in vitro for basic studies and translational applications such as adoptive cellular therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-11T18:56:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005287","title":"Twist_targeted_sequencing___KX002","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005288","title":"Twist_targeted_sequencing___KX003","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005289","title":"Twist_targeted_sequencing___KX004","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005290","title":"Twist_targeted_sequencing___KX007","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005291","title":"Twist_targeted_sequencing___KX008","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005292","title":"Twist_targeted_sequencing___SDS","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005293","title":"Twist_targeted_sequencing___SX001","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005294","title":"Twist_targeted_sequencing___TEST","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005295","title":"atrial appendage RNA-seq in non-, paroxysmal and persistent atrial fibrillation","description":"Understanding the interconnectedness of structural remodelling processes atrial fibrillation (AF) in patients could identify targets for future therapies. These data include transcriptome sequencing of atrial tissues of patients without AF, with paroxysmal AF and persistent AF (total n=64). In AF patients, epicardial cell gene expression decreased, contrasting with an upregulation of epithelial to mesenchymal transition (EMT) and mesenchymal cell gene expression. Immunohistochemistry demonstrated thickening of the epicardium and an increased proportion of (myo)fibroblast-like cells in the myocardium, supporting enhanced EMT in AF. We furthermore report an upregulation of endothelial cell proliferation, angiogenesis and endothelial signalling. EMT and endothelial cell proliferation concurred with increased interstitial (myo)fibroblast-like cells and extracellular matrix gene expression including enhanced tenascin-c, thrombospondins, biglycan and versican. Morphological analysis discovered increased and redistributed glycosaminoglycans and collagens in the atria of AF patients. Signalling pathways, including cell-matrix interactions, PI3K-AKT and Notch signalling, that could regulate mesenchymal cell activation, were upregulated. These dynamic processes may provide targets to prevent or reverse structural remodelling.","abstract":"Understanding the interconnectedness of structural remodelling processes atrial fibrillation (AF) in patients could identify targets for future therapies. These data include transcriptome sequencing of atrial tissues of patients without AF, with paroxysmal AF and persistent AF (total n=64). In AF patients, epicardial cell gene expression decreased, contrasting with an upregulation of epithelial to mesenchymal transition (EMT) and mesenchymal cell gene expression. Immunohistochemistry demonstrated thickening of the epicardium and an increased proportion of (myo)fibroblast-like cells in the myocardium, supporting enhanced EMT in AF. We furthermore report an upregulation of endothelial cell proliferation, angiogenesis and endothelial signalling. EMT and endothelial cell proliferation concurred with increased interstitial (myo)fibroblast-like cells and extracellular matrix gene expression including enhanced tenascin-c, thrombospondins, biglycan and versican. Morphological analysis discovered increased and redistributed glycosaminoglycans and collagens in the atria of AF patients. Signalling pathways, including cell-matrix interactions, PI3K-AKT and Notch signalling, that could regulate mesenchymal cell activation, were upregulated. These dynamic processes may provide targets to prevent or reverse structural remodelling.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-12T14:11:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005296","title":"Atrial appendage miRNA-seq in non-, paroxysmal and persistent atrial fibrillation","description":null,"abstract":"MiRNAs regulate posttranscriptional gene expression and are widely implicated in the pathogenesis of complex diseases. We aim to elucidate miRNA regulation of the atrial mRNA signatures that associate with AF. This may provide novel mechanistical insights and candidate targets for therapies using miRNA mimics or antimiRs. \nWe present combined miRNAs-mRNAs sequencing in atrial tissues of patient without AF (n=22), with paroxysmal AF (n=22) and with persistent AF (n=20). MiRNA and mRNA signatures followed an ordinal scale from nonAF to paroxysmal to persistent AF patients. The previously reported mRNA sequencing identified 5228 differentially expressed genes involved in epithelial to mesenchymal transition, endothelial cell proliferation and extracellular matrix remodelling involving collagens, glycoproteins and proteoglycans. We discovered 103 differentially expressed miRNAs. Key downregulated miRNAs included miR-135b-5p, miR-138-5p, miR-200a-3p, miR-200b-3p and miR-31-5p and key upregulated miRNAs were miR-144-3p, miR-15b-3p, miR-182-5p miR-18b-5p, miR-4306 and miR-206. The expression levels of differentially expressed miRNAs were negatively correlated with the expression levels of their predicted target mRNAs. The downregulated miRNAs demonstrated a more profound transcriptome effect than the upregulated miRNAs. Upregulated biological processes enriched in miRNAs targets related to epithelial and endothelial cell migration and glycosaminoglycan biosynthesis, in line with the processes discovered by the mRNA sequencing analysis. \nCombined analysis of miRNA and mRNA sequencing uncovered miRNAs with a broad transcriptional effect in human AF. Epithelial to mesenchymal transition and endothelial cell proliferation were processes controlled by downregulated miR-135b-5p, miR-138-5p, miR-200a-3p, miR-200b-3p and miR-31-5p, which in turn may contribute to (myo)fibroblast activation and structural remodeling.\\","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-12T14:24:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005297","title":"Single-cell profiling of the leukemic and non-leukemic immune cell compartments in CD8+ T-cell Large Granular Lymphocytic Leukemia","description":"We performed a detailed and precise characterisation of the clonally expanded leukemic cells in CD8+ T cell Large Granular Lymphocytic Leukemia (T-LGLL). By combining scRNA+TCRαβ-seq with bulk RNA sequencing data we showed evidence of a strong antigen-driven immune response that shapes the entire immune cell repertoire in T-LGLL. Our study highlights how the whole immune cell repertoire including the hyperexpanded CD8+ T-LGLL cells, the non-leukemic CD8+ cells, CD4+ cells, and monocytes contribute to the CD8+ T-LGLL disease phenotype.\n\nPlease note that this submission contains the fastq files while the processed count matrices can be found in ArrayExpress by the accession E-MTAB-11170.","abstract":"We performed a detailed and precise characterisation of the clonally expanded leukemic cells in CD8+ T cell Large Granular Lymphocytic Leukemia (T-LGLL). By combining scRNA+TCRαβ-seq with bulk RNA sequencing data we showed evidence of a strong antigen-driven immune response that shapes the entire immune cell repertoire in T-LGLL. Our study highlights how the whole immune cell repertoire including the hyperexpanded CD8+ T-LGLL cells, the non-leukemic CD8+ cells, CD4+ cells, and monocytes contribute to the CD8+ T-LGLL disease phenotype.\n\nPlease note that this submission contains the fastq files while the processed count matrices can be found in ArrayExpress by the accession E-MTAB-11170.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-12T14:59:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005298","title":"HSC_colony_many_years_post_allogeneic_bone_marrow_transplant_TGS","description":"This study looks at human donors and recipients of allogeneic blood &amp; marrow marrow transplantation. Each transplant \"pair\" (donor &amp; recipient) underwent the transplant procedure 10 -30 years prior to sampling - the majority for an underlying diagnosis of leukemia.  We will perform whole-genome sequencing on tens to hundreds of single HSPC (haematopoietic stem and progenitor cell)-derived colonies per individual. We will infer the phylogeny of these cells (those from both donor &amp; recipient within a pair) by analysing the somatically acquired mutations within each cell. The structure of the phylogeny will allow estimates of hitherto unknown parameters such as the number of HSCs that engraft long-term, the dynamics of the engraftment process on the HSC level, and the additional mutation burden acquired through the arduous transplant procedure.\nThis TGS part of the study is used for assessing the contribution of clones to mature blood subsets, and better timing mutations relative to transplantation.","abstract":"We propose the use of whole genome sequencing, along with state-of-the-art phylogenetic methods, to reconstruct the dynamics of stem cell engraftment in patients undergoing allogeneic stem cell transplantation for haematological disease:\n\t\n-\tHow many infused haematopoietic stem cells successfully engraft and contribute to subsequent haematopoiesis in human recipients?\n-\tWhat is the time course and phylogenetic structure of stem cell reconstitution?\n-\tAre the outputs of individual engrafting stem_cells biased towards particular lineages e.g. myeloid vs B/T lymphoid?\n\nWithin our study cohort we anticipate a variety of recipient/ donor characteristics, conditioning regimens (myeloablative or reduced-intensity) and other transplant variables (e.g. transplanted cell dose).  Although this study will not have statistical power to draw definitive conclusions on how these differences affect transplant phylodynamics it will establish proof of principle for this type of analysis and inform hypotheses for future studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-12T16:56:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005299","title":"ALLoreactive T-Cell receptOr RePertoire in kidnEy tranSplantation","description":"A prospective study for investigating the T-cell receptor (TCR) repertoire in T-cell mediated rejection (TCMR) after kidney transplantation. The pre-formed donor-reactive TCR repertoire was tracked in blood and tissue of patients after kidney transplantation and characteristics of TCR repertoires from patients experiencing a rejection were compared to patients with no histopathological signs of rejection.","abstract":"A prospective study for investigating the T-cell receptor (TCR) repertoire in T-cell mediated rejection (TCMR) after kidney transplantation. The pre-formed donor-reactive TCR repertoire was tracked in blood and tissue of patients after kidney transplantation and characteristics of TCR repertoires from patients experiencing a rejection were compared to patients with no histopathological signs of rejection.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-14T14:53:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005300","title":"Multimodal single-cell and bulk glioma analyses","description":"Glioma intratumoral heterogeneity enables adaptation to challenging microenvironments and contributes to therapeutic resistance. We integrated 914 single-cell DNA methylomes, 55,284 single-cell transcriptomes, and bulk multi-omic profiles across 11 adult IDH-mutant or IDH-wild-type gliomas to delineate sources of intratumoral heterogeneity. We show that local DNA methylation disorder associates with cell-to-cell DNA methylation differences, is elevated in more aggressive tumors, links with transcriptional disruption, and is altered in environmental stress response. Glioma cells under in vitro hypoxic and irradiation stress increased local DNA methylation disorder and shifted cell states. We identified a positive association between genetic and epigenetic instability that was supported in bulk longitudinally collected DNA methylation data. Increased DNA methylation disorder associated with accelerated disease progression, and recurrently selected DNA methylation changes were enriched for environmental stress response pathways. Our work identifies an epigenetically facilitated adaptive stress response process and highlights the importance of epigenetic heterogeneity in shaping therapeutic outcomes.","abstract":"Glioma intratumoral heterogeneity enables adaptation to challenging microenvironments and contributes to therapeutic resistance. We integrated 914 single-cell DNA methylomes, 55,284 single-cell transcriptomes, and bulk multi-omic profiles across 11 adult IDH-mutant or IDH-wild-type gliomas to delineate sources of intratumoral heterogeneity. We show that local DNA methylation disorder associates with cell-to-cell DNA methylation differences, is elevated in more aggressive tumors, links with transcriptional disruption, and is altered in environmental stress response. Glioma cells under in vitro hypoxic and irradiation stress increased local DNA methylation disorder and shifted cell states. We identified a positive association between genetic and epigenetic instability that was supported in bulk longitudinally collected DNA methylation data. Increased DNA methylation disorder associated with accelerated disease progression, and recurrently selected DNA methylation changes were enriched for environmental stress response pathways. Our work identifies an epigenetically facilitated adaptive stress response process and highlights the importance of epigenetic heterogeneity in shaping therapeutic outcomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-15T16:43:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005301","title":"Circulating tumor cell copy-number heterogeneity in ALK-rearranged non-small-cell lung cancer resistant to ALK inhibitors","description":"Gatekeeper mutations are identified in only 50% of the cases at resistance to Anaplastic Lymphoma Kinase (ALK)-tyrosine kinase inhibitors (TKIs). Circulating tumor cells (CTCs) are relevant tools to identify additional resistance mechanisms and can be sequenced at the single-cell level. Here, we provide in-depth investigation of copy number alteration (CNA) heterogeneity in phenotypically characterized CTCs at resistance to ALK-TKIs in ALK-positive non-small cell lung cancer.","abstract":"Gatekeeper mutations are identified in only 50% of the cases at resistance to Anaplastic Lymphoma Kinase (ALK)-tyrosine kinase inhibitors (TKIs). Circulating tumor cells (CTCs) are relevant tools to identify additional resistance mechanisms and can be sequenced at the single-cell level. Here, we provide in-depth investigation of copy number alteration (CNA) heterogeneity in phenotypically characterized CTCs at resistance to ALK-TKIs in ALK-positive non-small cell lung cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-15T20:30:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005302","title":"HCA_Bladder_Adult_WSSS_RNA","description":"Cell atlas of the human bladder","abstract":"RNA-Seq for bladder cells The aim of this study to assess the single cell gene expression profile in the bladder. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005303","title":"ChIP-seq in colorectal cancer and paired adjacent normal mucosa","description":"Chip-seq samples for 20 colorectal patients with paired adjacent normal mucosa to characterize H3K27ac and H3K4me1.","abstract":"Chip-seq samples for 20 colorectal patients with paired adjacent normal mucosa to characterize H3K27ac and H3K4me1.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-17T10:22:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005304","title":"COVID19 Host Genetic Initiative","description":"The COVID-19 host genetics initiative is a bottom-up collaborative effort that has three main goals: 1. Provide an environment to foster the sharing of resources to facilitate COVID-19 host genetics research (e.g. protocols, questionnaires). 2. Organize analytical activities across studies to identify genetic determinants of COVID-19 susceptibility and severity. 3. Provide a platform to share the results from such activities, as well as the individual-level data where possible, to benefit the broader scientific community. Here, we release the harmonized individual-level data for the subset of individuals who participated in COVID-19 HGI.\n\nPlease refer to this data dictionary: https://docs.google.com/spreadsheets/d/1whu_MjShXxbdoAJMCYxZ5C-vWOcRivwfWglTcBRNZgQ/edit#gid=470747846\n\nPlease cite both Nakanishi, T el al. J Clin Invest 2021 (PMID: 34597274) and COVID-19 Host Genetics Initiative, Nature 2021 (PMID: 34237774) when you use these data for your publications.","abstract":"The COVID-19 host genetics initiative is a bottom-up collaborative effort that has three main goals: 1. Provide an environment to foster the sharing of resources to facilitate COVID-19 host genetics research (e.g. protocols, questionnaires). 2. Organize analytical activities across studies to identify genetic determinants of COVID-19 susceptibility and severity. 3. Provide a platform to share the results from such activities, as well as the individual-level data where possible, to benefit the broader scientific community. Here, we release the harmonized individual-level data for the subset of individuals who participated in COVID-19 HGI.\n\nPlease refer to this data dictionary: https://docs.google.com/spreadsheets/d/1whu_MjShXxbdoAJMCYxZ5C-vWOcRivwfWglTcBRNZgQ/edit#gid=470747846\n\nPlease cite both Nakanishi, T el al. J Clin Invest 2021 (PMID: 34597274) and COVID-19 Host Genetics Initiative, Nature 2021 (PMID: 34237774) when you use these data for your publications.","study_type":"Other","pubmed_ids":[34237774],"external_links":null,"is_released":true,"released_date":"2021-05-17T11:30:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005305","title":"Bulk-tissue RNA-sequencing of anterior cingulate cortex samples derived from Lewy body disease patients","description":"Parkinson’s disease (PD), Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB) are three clinically, genetically and neuropathologically overlapping neurodegenerative diseases collectively known as the Lewy body diseases (LBDs). A variety of molecular mechanisms have been implicated in PD pathogenesis, but the mechanisms underlying PDD and DLB remain largely unknown, a knowledge gap that presents an impediment to the discovery of disease-modifying therapies. Transcriptomic profiling can contribute to addressing this gap, but remains limited in the LBDs. Here, we applied paired bulk-tissue and single-nucleus RNA-sequencing to anterior cingulate cortex samples derived from 28 individuals, including healthy controls, PD, PDD and DLB cases (n = 7 per group), to transcriptomically profile the LBDs. Using this approach, we (i) found transcriptional alterations in multiple cell types across the LBDs; (ii) discovered evidence for widespread dysregulation of RNA splicing, particularly in PDD and DLB; (iii) identified potential splicing factors, with links to other dementia-related neurodegenerative diseases, coordinating this dysregulation; and (iv) identified transcriptomic commonalities and distinctions between the LBDs that inform understanding of the relationships between these three clinical disorders. Together, these findings have important implications for the design of RNA-targeted therapies for these diseases and highlight a potential molecular “window” of therapeutic opportunity between the initial onset of PD and subsequent development of Lewy body dementia.","abstract":"Parkinson’s disease (PD), Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB) are three clinically, genetically and neuropathologically overlapping neurodegenerative diseases collectively known as the Lewy body diseases (LBDs). A variety of molecular mechanisms have been implicated in PD pathogenesis, but the mechanisms underlying PDD and DLB remain largely unknown, a knowledge gap that presents an impediment to the discovery of disease-modifying therapies. Transcriptomic profiling can contribute to addressing this gap, but remains limited in the LBDs. Here, we applied paired bulk-tissue and single-nucleus RNA-sequencing to anterior cingulate cortex samples derived from 28 individuals, including healthy controls, PD, PDD and DLB cases (n = 7 per group), to transcriptomically profile the LBDs. Using this approach, we (i) found transcriptional alterations in multiple cell types across the LBDs; (ii) discovered evidence for widespread dysregulation of RNA splicing, particularly in PDD and DLB; (iii) identified potential splicing factors, with links to other dementia-related neurodegenerative diseases, coordinating this dysregulation; and (iv) identified transcriptomic commonalities and distinctions between the LBDs that inform understanding of the relationships between these three clinical disorders. Together, these findings have important implications for the design of RNA-targeted therapies for these diseases and highlight a potential molecular “window” of therapeutic opportunity between the initial onset of PD and subsequent development of Lewy body dementia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-18T06:32:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005306","title":"GWAS data on controls of the PROGENE French study (epidemiological and genetics study on prostate cancer)","description":null,"abstract":"GWAS data on 496 controls (without prostate cancer) of European Caucasian origin, genotyped for the Illumina Infinium Global Screening Array-24 v3.0 chip.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005307","title":"BARIA bariatric surgery metagenomics","description":null,"abstract":"Study the effect of bariatric surgery on the gut microbiome, and vise versa","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005308","title":"RNAseq liver biopsies","description":null,"abstract":"RNAseq profile liverbiopsies NAFLD NASH","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005309","title":"RNAseq visceral_fat biopsies","description":null,"abstract":"RNAseq visceral_fat biopsies","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005310","title":"RNAseq jejunum biopsies","description":null,"abstract":"RNAseq jejunum biopsies","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005311","title":"RNAseq subcutaneous_fat biopsies","description":null,"abstract":"RNAseq subcutaneous_fat biopsies","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005312","title":"Genomic Rearrangements in Pediatric Cancer","description":"This study contains a collection of samples used to determine the role and impact of genomic rearrangements in a pan cancer pediatric cohort.","abstract":"This study contains a collection of samples used to determine the role and impact of genomic rearrangements in a pan cancer pediatric cohort.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-19T10:36:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005313","title":"Genomic Analysis of Focal Nodular Hyperplasia with Associated Hepatocellular Carcinoma Unveils its Malignant Potential","description":null,"abstract":"Focal nodular hyperplasia (FNH) is defined as a benign tumor of the liver without malignant potential. In this study, we reported a 74-year-old female patient with an FNH and associated concomitant hepatocellular carcinoma (HCC). Immunophenotypic and genomic analyses revealed that FNH may be composed of multiple clones at diagnosis, that are likely to progress to HCC through clonal selection and/or the acquisition of additional genetic events. This report suggests that FNH may possess the capability to undergo a malignant transformation, bringing into evidence the potential progress to HCC of this lesion in very rare cases.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-19T12:46:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005314","title":"Evolutionary predictability of genetic versus non genetic resistance to anticancer drugs in melanoma","description":"Therapy resistance arises from heterogeneous drug-tolerant persister cells or minimal residual disease (MRD) through genetic and nongenetic mechanisms. A key question is whether specific molecular features of the MRD ecosystem determine which of these two distinct trajectories will eventually prevail. We show that, in melanoma exposed to MAPK therapeutics, emergence of a transient neural crest stem cell (NCSC) population in MRD concurs with the development of nongenetic resistance. This increase relies on a GDNF-dependent signaling cascade, which activates the AKT survival pathway in a focal adhesion kinase (FAK)-dependent manner. Ablation of the NCSC population through FAK inhibition delays relapse in patient-derived tumor xenografts. Strikingly, all tumors that ultimately escape this treatment exhibit resistance-conferring genetic alterations and increased sensitivity to ERK inhibition. These findings identify an approach that abrogates the nongenetic resistance trajectory in melanoma and demonstrate that the cellular composition of MRD deterministically imposes distinct drug resistance evolutionary paths.","abstract":"Therapy resistance arises from heterogeneous drug-tolerant persister cells or minimal residual disease (MRD) through genetic and nongenetic mechanisms. A key question is whether specific molecular features of the MRD ecosystem determine which of these two distinct trajectories will eventually prevail. We show that, in melanoma exposed to MAPK therapeutics, emergence of a transient neural crest stem cell (NCSC) population in MRD concurs with the development of nongenetic resistance. This increase relies on a GDNF-dependent signaling cascade, which activates the AKT survival pathway in a focal adhesion kinase (FAK)-dependent manner. Ablation of the NCSC population through FAK inhibition delays relapse in patient-derived tumor xenografts. Strikingly, all tumors that ultimately escape this treatment exhibit resistance-conferring genetic alterations and increased sensitivity to ERK inhibition. These findings identify an approach that abrogates the nongenetic resistance trajectory in melanoma and demonstrate that the cellular composition of MRD deterministically imposes distinct drug resistance evolutionary paths.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-19T15:52:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005315","title":"Genome-wide data from Agta hunter-gatherers in Philippines","description":"To investigate the relationship between host genetics and the oral microbiome composition of Agta hunter-gatherers from the Philippines, we genotyped the Agta population (hunter-gatherers from Philippines) together with BaYaka (hunter-gatherers from Congo) and Palanan farmers (neighbouring population of the Agta).","abstract":"To investigate the relationship between host genetics and the oral microbiome composition of Agta hunter-gatherers from the Philippines, we genotyped the Agta population (hunter-gatherers from Philippines) together with BaYaka (hunter-gatherers from Congo) and Palanan farmers (neighbouring population of the Agta).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-19T15:58:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005316","title":"Targeted sequencing of 13131 older individuals, using 750-gene panel","description":null,"abstract":"A custom sequencing panel of 762 genes with known disease-associations was designed using AmpliSeq (Thermo Fisher Scientific). Following standard protocols, DNA was extracted and sequenced using the Thermo Fisher Scientific S5TM XL system, to average 200X depth across exonic regions.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005317","title":"Oral microbiome composition of Agta hunter-gatherers (16S)","description":"To investigate the factors affecting the composition of the oral microbiome of Agta hunter-gatherers from the Philippines, we sequenced the 16S rRNA region from saliva samples from the Agta population (hunter-gatherers from Philippines) together with BaYaka (hunter-gatherers from Congo) and Palanan farmers (neighboring population of the Agta).","abstract":"To investigate the factors affecting the composition of the oral microbiome of Agta hunter-gatherers from the Philippines, we sequenced the 16S rRNA region from saliva samples from the Agta population (hunter-gatherers from Philippines) together with BaYaka (hunter-gatherers from Congo) and Palanan farmers (neighboring population of the Agta).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-19T23:23:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005318","title":"Evolution of castration-resistant prostate cancer in ctDNA during sequential androgen receptor pathway inhibition","description":null,"abstract":"Cross-resistance renders multiple lines of androgen receptor (AR) signaling inhibitors increasingly futile in metastatic castration-resistant prostate cancer (mCRPC). To determine acquired genomic contributors to cross-resistance, we applied deep targeted and whole exome sequencing to 458 serial plasma cell-free DNA samples from 202 mCRPC patients receiving sequential AR signaling inhibitors in a phase II clinical trial.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005319","title":"Microbiota, Appetite, and Malnutrition in Dutch Community-dwelling older adults","description":null,"abstract":"This concerns a cross-sectional cohort study of 356 Dutch community-dwelling older adults to study the association of the oral microbiota with poor taste, poor smell, poor appetite and undernutrition. Data-collection consisted of body measurements (incl. body weight, height, and body impedance analysis), extensive appetite and food frequency questionnaires, taste and smell tests, and a tongue swab. The oral microbiota composition was assessed with 16S rRNA sequencing.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-20T12:20:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005320","title":"Secondary Resistance to Anti-EGFR Therapy by Transcriptional Reprogramming in Patient-Derived Colorectal Cancer Models (hipo_B012)","description":null,"abstract":"The development of secondary resistance (SR) in metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (anti-EGFR) antibodies is not fully understood at the molecular level. Here we tested in vivo selection of anti-EGFR SR tumors in 2 CRC patient-derived xenograft (PDX) models as a strategy for a molecular dissection of SR mechanisms. We analyzed 21 KRAS, NRAS, BRAF, and PI3K wild-type CRC patient-derived xenograft (PDX) models for their anti-EGFR sensitivity. Furthermore, 31 anti-EGFR SR tumors were generated via chronic in vivo treatment with cetuximab. A multi-omics approach was employed to address molecular primary and secondary resistance mechanisms. Gene set enrichment analyses were used to uncover SR pathways. Targeted therapy of SR PDX models was applied to validate selected SR pathways.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-21T09:33:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005321","title":"Pediatric tumor in a single child of three large nuclear families","description":"We identify three nuclear families in which a pediatric tumor had been diagnosed in a single child and neither parent had been diagnosed with cancer. These families had 4, 5, and 7 children, respectively. Diagnoses included Wilms tumor, low-grade astrocytoma, and Burkitt’s lymphoma, respectively. We used whole-genome sequencing to profile normal cells from each family member and a linked-read technology for genomic phasing, which enabled us to identify compound-heterozygous and de novo variants in addition to simple-heterozygous and homozygous-alternate variants.","abstract":"We identify three nuclear families in which a pediatric tumor had been diagnosed in a single child and neither parent had been diagnosed with cancer. These families had 4, 5, and 7 children, respectively. Diagnoses included Wilms tumor, low-grade astrocytoma, and Burkitt’s lymphoma, respectively. We used whole-genome sequencing to profile normal cells from each family member and a linked-read technology for genomic phasing, which enabled us to identify compound-heterozygous and de novo variants in addition to simple-heterozygous and homozygous-alternate variants.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-21T18:02:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005322","title":"Neuroblastoma tumor heterogeneity and cell plasticity (from patients)","description":"Two cell identities, noradrenergic and mesenchymal, have been characterized in neuroblastoma cell lines according to their epigenetic landscapes relying on specific core regulatory circuitries of transcription factors. Yet, their relationship and relative contribution in patient tumors remain to be defined. Here, we document a spontaneous plasticity between the noradrenergic and mesenchymal identities in a subset of cell lines. Strikingly, mesenchymal neuroblastoma cells revert to a noradrenergic phenotype in vivo. Consistently, tumor cells with a mesenchymal identity are detected in single-cell transcriptomic analyses of neuroblastoma tumors and PDX models. Our data also highlight neuroblastoma intra-tumor heterogeneity with the co-existence of distinct tumor populations, including sympathoblast-like and chromaffin-like cells suggesting that neuroblastoma cells arise from a common sympatho-adrenal progenitor.","abstract":"Two cell identities, noradrenergic and mesenchymal, have been characterized in neuroblastoma cell lines according to their epigenetic landscapes relying on specific core regulatory circuitries of transcription factors. Yet, their relationship and relative contribution in patient tumors remain to be defined. Here, we document a spontaneous plasticity between the noradrenergic and mesenchymal identities in a subset of cell lines. Strikingly, mesenchymal neuroblastoma cells revert to a noradrenergic phenotype in vivo. Consistently, tumor cells with a mesenchymal identity are detected in single-cell transcriptomic analyses of neuroblastoma tumors and PDX models. Our data also highlight neuroblastoma intra-tumor heterogeneity with the co-existence of distinct tumor populations, including sympathoblast-like and chromaffin-like cells suggesting that neuroblastoma cells arise from a common sympatho-adrenal progenitor.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-25T10:49:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005323","title":"Systematic evaluation of NIPT aneuploidy detection software tools with clinically validated NIPT samples","description":"Non-invasive prenatal testing (NIPT) is a powerful screening method for fetal aneuploidy detection, relying on laboratory and computational analysis of cell-free DNA. Although several published computational NIPT analysis tools are available, no comprehensive and direct accuracy evaluations of these tools is published. Here, we evaluate and determine the precision of five commonly used computational NIPT aneuploidy analysis tools, considering diverse sequencing depth (coverage), arbitrary sequencing read placement, and fetal DNA fraction on clinically validated NIPT samples.","abstract":"Non-invasive prenatal testing (NIPT) is a powerful screening method for fetal aneuploidy detection, relying on laboratory and computational analysis of cell-free DNA. Although several published computational NIPT analysis tools are available, no comprehensive and direct accuracy evaluations of these tools is published. Here, we evaluate and determine the precision of five commonly used computational NIPT aneuploidy analysis tools, considering diverse sequencing depth (coverage), arbitrary sequencing read placement, and fetal DNA fraction on clinically validated NIPT samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-25T14:04:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005324","title":"HCA_Kidney_Adult_MRC_RNA_BS","description":"Regional diversity in transcriptional and epigenomic cellular programmes in the human kidney","abstract":"The human kidney is the master regulator of whole organism homeostasis, and achieves a control of acid-base and electrolyte homeostasis along with endocrine regulation of erythropoiesis and blood pressure. Substantial regional variation in cellular populations, activities, and extracellular environments exists in the kidney, including cortico-medullary gradients of osmolality and hypoxia. This study will profile cellular populations through cortico-medullary depth using high throughput joint single-nucleus RNAseq and ATACseq, generating a large scale atlas to probe genomic correlates of regional diversity in the human kidney.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-25T18:47:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005325","title":"Robust detection of translocations in lymphoma FFPE samples using Targeted Locus Capture-based sequencing - NGS targeted capture control cohort","description":"In routine diagnostic pathology, cancer biopsies are preserved by Formalin-Fixed, Paraffin-Embedding (FFPE) procedures for examination of (intra-) cellular morphology. Such procedures inadvertently induce DNA fragmentation, which compromises sequencing-based analyses of chromosomal rearrangements. Yet, rearrangements drive many types of hematolymphoid malignancies and solid tumors, and their manifestation is instructive for diagnosis, prognosis and treatment. Here, we present FFPE-Targeted Locus Capture (FFPE-TLC) for targeted sequencing of proximity-ligation products formed in FFPE tissue blocks, and PLIER, a computational framework that allows automated identification and characterization of rearrangements involving selected, clinically-relevant, loci. FFPE-TLC, blindly applied to 149 lymphoma and control FFPE samples, identifies the known and novel rearrangement partners. It outperforms fluorescence in situ hybridization (FISH) in sensitivity and specificity, and shows clear advantages over standard capture-NGS methods, finding rearrangements involving repetitive sequences which they typically miss. FFPE-TLC is therefore a powerful clinical diagnostics tool for accurate targeted rearrangement detection in FFPE specimens.","abstract":"In routine diagnostic pathology, cancer biopsies are preserved by Formalin-Fixed, Paraffin-Embedding (FFPE) procedures for examination of (intra-) cellular morphology. Such procedures inadvertently induce DNA fragmentation, which compromises sequencing-based analyses of chromosomal rearrangements. Yet, rearrangements drive many types of hematolymphoid malignancies and solid tumors, and their manifestation is instructive for diagnosis, prognosis and treatment. Here, we present FFPE-Targeted Locus Capture (FFPE-TLC) for targeted sequencing of proximity-ligation products formed in FFPE tissue blocks, and PLIER, a computational framework that allows automated identification and characterization of rearrangements involving selected, clinically-relevant, loci. FFPE-TLC, blindly applied to 149 lymphoma and control FFPE samples, identifies the known and novel rearrangement partners. It outperforms fluorescence in situ hybridization (FISH) in sensitivity and specificity, and shows clear advantages over standard capture-NGS methods, finding rearrangements involving repetitive sequences which they typically miss. FFPE-TLC is therefore a powerful clinical diagnostics tool for accurate targeted rearrangement detection in FFPE specimens.","study_type":"Other","pubmed_ids":[34099699],"external_links":null,"is_released":true,"released_date":"2021-05-26T08:17:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005326","title":"Immune infiltrate and tumor microenvironment transcriptional programs stratify pediatric osteosarcoma into prognostic groups at diagnosis","description":null,"abstract":"Outcomes for adolescents/young adults with osteosarcoma has not improved since decades. Chaotic karyotype of this rare tumor has precluded identification of prognostic biomarkers/stratification. We reasoned that transcriptomic study should overcome this genetic complexity. From the RNA-sequencing of 79 osteosarcomas diagnostic biopsies, we identified stable independent components (Metagenes) recapitulating the tumor microenvironment and clones. Metagene unsupervised classification stratified this cohort into good (G1) and poor (G2) prognostic tumors on overall survival. Multivariate survival analysis ranked this stratification as the most influential variable. Functional characterization associates G1 tumors with innate immunity and G2 tumors with angiogenic, osteoclastic and adipogenic activities as well as PPAR pathway upregulation. We next defined a short gene signature to predict G1/G2 tumors from RNA-seq validated within independent cohort of 82 osteosarcomas. We further validated the signature by custom Nanostring panel in 96 additional osteosarcomas. Our study thus proposes new biomarkers to detect hard-to-treat patients as well as related new therapeutic options.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-26T10:06:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005327","title":"Identification of early disease progression in ALK-rearranged lung cancer using circulating tumor DNA analysis (hipo_K34R)","description":null,"abstract":"We utilized 343 longitudinal plasma DNA samples from 43 ALK+ NSCLC patients receiving targeted ALK therapy to evaluate ctDNA levels based on matched panel-based targeted next generation sequencing (tNGS) and untargeted shallow whole genome sequencing (sWGS). We measured the mean variant allele frequency (VAFmean) of genetic alterations called by tNGS and applied the t-MAD score as surrogate for the global copy number changes reflected by ctDNA. Both NGS metrics were assessed as indicators of disease progression, and more importantly, early molecular progression. Systematic establishment of thresholds in VAFmean and t-MAD changes indicating clinical progression was performed in our study cohort.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-26T12:11:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005328","title":"Multi-site tumor sampling highlights molecular intra-tumor heterogeneity in malignant pleural mesothelioma","description":"Background:Malignant pleural mesothelioma (MPM) is a heterogeneous cancer. Better knowledge of molecular and cellular intra-tumor heterogeneity throughout the thoracic cavity is required to develop efficient therapies. This study focuses on molecular intra-tumor heterogeneity using the largest series to date in MPM and is the first to report on the multi-omics profiling of a substantial series of multi-site tumor samples. Methods:Intra-tumor heterogeneity was investigated in 16 patients from whom biopsies were taken at distinct anatomical sites. The paired biopsies collected from apex, side wall, costo-diaphragmatic or highest metabolic sites as well as 5 derived cell lines were screened using targeted sequencing. Whole exome sequencing, RNA sequencing, and DNA methylation were performed on a subset of the cohort for deep characterization. Molecular classification, recently defined histo-molecular gradients, and cell populations of the tumor microenvironment were assessed. Results:Sequencing analysis identified heterogeneous variants notably in NF2, a key tumor suppressor gene of mesothelial carcinogenesis. Subclonal tumor populations were shared among paired biopsies, suggesting a polyclonal dissemination of the tumor. Transcriptome analysis highlighted dysregulation of cell adhesion and extracellular matrix pathways, linked to changes in histo-molecular gradient proportions between anatomic sites. Methylome analysis revealed contribution of epigenetic mechanisms in two patients. Finally, significant changes in the expression of immune mediators and genes related to immunological synapse, as well as differential infiltration of immune populations in the tumor environment were observed and led to a switch from a hot to a cold immune profile in three patients.  Conclusions:This comprehensive analysis reveals patient-dependent spatial intra-tumor heterogeneity at the genetic, transcriptomic and epigenetic levels and in the immune landscape of the tumor microenvironment. Results support","abstract":"Background:Malignant pleural mesothelioma (MPM) is a heterogeneous cancer. Better knowledge of molecular and cellular intra-tumor heterogeneity throughout the thoracic cavity is required to develop efficient therapies. This study focuses on molecular intra-tumor heterogeneity using the largest series to date in MPM and is the first to report on the multi-omics profiling of a substantial series of multi-site tumor samples. Methods:Intra-tumor heterogeneity was investigated in 16 patients from whom biopsies were taken at distinct anatomical sites. The paired biopsies collected from apex, side wall, costo-diaphragmatic or highest metabolic sites as well as 5 derived cell lines were screened using targeted sequencing. Whole exome sequencing, RNA sequencing, and DNA methylation were performed on a subset of the cohort for deep characterization. Molecular classification, recently defined histo-molecular gradients, and cell populations of the tumor microenvironment were assessed. Results:Sequencing analysis identified heterogeneous variants notably in NF2, a key tumor suppressor gene of mesothelial carcinogenesis. Subclonal tumor populations were shared among paired biopsies, suggesting a polyclonal dissemination of the tumor. Transcriptome analysis highlighted dysregulation of cell adhesion and extracellular matrix pathways, linked to changes in histo-molecular gradient proportions between anatomic sites. Methylome analysis revealed contribution of epigenetic mechanisms in two patients. Finally, significant changes in the expression of immune mediators and genes related to immunological synapse, as well as differential infiltration of immune populations in the tumor environment were observed and led to a switch from a hot to a cold immune profile in three patients.  Conclusions:This comprehensive analysis reveals patient-dependent spatial intra-tumor heterogeneity at the genetic, transcriptomic and epigenetic levels and in the immune landscape of the tumor microenvironment. Results support","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-26T13:34:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005329","title":"Exome Sequecning of MDS xenografted samples","description":"Pre-clinical research of Myelodysplastic Syndromes (MDS) is hampered by a lack of feasible disease models. Previously, we have established a robust patient-derived xenograft (PDX) model for MDS. Here, we demonstrate for the first time that this model is applicable as a pre-clinical platform to address pending clinical questions by interrogating the efficacy and safety of the thrombopoietin receptor agonist eltrombopag. Our pre-clinical study included n=49 xenografts generated from n=9 MDS patient samples. Substance efficacy was evidenced by FACS-based human platelet quantification, and clonal bone marrow evolution was reconstructed by serial whole exome sequencing of the PDX samples. In contrast to clinical trials in humans, this experimental setup allowed vehicle- and replicate-controlled analyses on a patient-individual level deciphering substance-specific effects from natural disease progression. We found that eltrombopag effectively stimulated thrombopoiesis in MDS PDX without adversely affecting the patients’ clonal composition. In conclusion, our MDS PDX model is a useful tool for testing new therapeutic concepts in MDS preceding clinical trials.","abstract":"Pre-clinical research of Myelodysplastic Syndromes (MDS) is hampered by a lack of feasible disease models. Previously, we have established a robust patient-derived xenograft (PDX) model for MDS. Here, we demonstrate for the first time that this model is applicable as a pre-clinical platform to address pending clinical questions by interrogating the efficacy and safety of the thrombopoietin receptor agonist eltrombopag. Our pre-clinical study included n=49 xenografts generated from n=9 MDS patient samples. Substance efficacy was evidenced by FACS-based human platelet quantification, and clonal bone marrow evolution was reconstructed by serial whole exome sequencing of the PDX samples. In contrast to clinical trials in humans, this experimental setup allowed vehicle- and replicate-controlled analyses on a patient-individual level deciphering substance-specific effects from natural disease progression. We found that eltrombopag effectively stimulated thrombopoiesis in MDS PDX without adversely affecting the patients’ clonal composition. In conclusion, our MDS PDX model is a useful tool for testing new therapeutic concepts in MDS preceding clinical trials.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-26T16:13:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005330","title":"An approach for evaluating the effects of dietary fiber polysaccharides on the human gut microbiome and plasma proteome","description":null,"abstract":"The worldwide increase in snack-food consumption associated with adoption of Westernized lifestyles provides an opportunity to introduce new nutritious foods into non-nutritious diets. We describe two 10-week-long pilot studies of obese or overweight individuals measured the effects of pea fiber- or orange fiber-containing snack food prototypes on the abundances of fecal microbiome glycoside hydrolases (GH) and polysaccharide lyases (PL), fecal glycan metabolism, and &amp;gt;1300 plasma proteins. Computational methods for feature selection plus contextual language processing software that extracts information from all PubMed abstracts referencing features of interest, identified treatment-discriminatory changes in GH and PL gene abundances that correlated with levels of fecal glycosidic linkages related to fiber metabolism, and plasma proteins representing diverse biological themes, including TGFβ/BMP-mediated fibrotic responses, VEGF-related angiogenic responses, P38/MAPK-associated immune cell biomarkers, and obesity-associated hormonal regulators. These results disclose fiber-snack prototype effects on microbiome function and host physiology in the context of varying background dietary practices.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-27T03:08:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005331","title":"Correction of FFPE artefacts in WGS data","description":"The ability to precisely characterise mutational signatures from FFPE-derived DNA has tremendous translational potential.  However, sequencing of DNA derived from FFPE material is known to be riddled with artefacts. To correct for this, we introduce FFPEsig, a computational algorithm to rectify the formalin-induced artefacts in the mutational profile.","abstract":"The ability to precisely characterise mutational signatures from FFPE-derived DNA has tremendous translational potential.  However, sequencing of DNA derived from FFPE material is known to be riddled with artefacts. To correct for this, we introduce FFPEsig, a computational algorithm to rectify the formalin-induced artefacts in the mutational profile.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-27T11:18:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005332","title":"COVID-19 whole blood transcriptomic analysis","description":null,"abstract":"In a study of 207 SARS-CoV2-infected individuals with a range of severities followed over 12 weeks from symptom onset, we demonstrate that an early robust bystander CD8 T cell immune response, without systemic inflammation, is characteristic of asymptomatic or mild disease. Those presenting to hospital had delayed bystander responses and systemic inflammation already evident at around symptom onset. Such early evidence of inflammation suggests immunopathology may be inevitable in some individuals, or that preventative intervention might be needed before symptom onset. Viral load does not correlate with the development of this pathological response, but does with its subsequent severity. Immune recovery is complex, with profound persistent cellular abnormalities correlating with a change in the nature of the inflammatory response, where signatures characteristic of increased oxidative phosphorylation and reactive-oxygen species-associated inflammation replace those driven by TNF and IL-6. These late immunometabolic inflammatory changes and unresolved immune defects may have clinical implications.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-27T15:33:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005333","title":"Breast_CIS_WGS","description":"LCM guided multiregion sequencing of breast tissues to examine patterns of cancer progression and growth.","abstract":"To understand the diverse evolutionary trajectories of healthy and cancerous breast tissue cells we are using spatially resolved molecular analyses in normal tissues and breast cancers from the earliest stage of disease (pre-invasive), through to the stages of tissue invasion. Laser capture microscopy and genomic profiling will reveal the extent of genomic diversity in the breast samples studied here. Individual subclones, defined by their genotype will then be mapped in breast tissues in space and time using spatial profiling approaches. Spatial localisation will allow individual subclones to be studied in the context of the histological structure, in relation to localised immune infiltrates and normal tissue responses.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005334","title":"Whole_breast_profiling_WGS","description":"Deep genomic profiling of normal and neoplastic tissues to chart the development of the breast and the transition to disease.","abstract":"All tissues continuously acquire mutations. Combining laser capture microscopy, low input genomic sequencing and lineage tracing techniques to 'whole breast' specimens we will chart how the tissue develops over space and time. This data will then be integrated with other omic approaches to provide further insights such as the interaction between different clones and the microenvironment.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005335","title":"Breast_clonal_dynamics_across_chemotherapy_WES","description":"Mapping the clonal landscape in breast cancers across treatment.","abstract":"Cancer arises through a combination of mutation and selection. Chemotherapy can obliterate some cancers but some cancers exhibit treatment resistance whereby some clones continue to grow or new clones emerge. This may reflect intrinsic features of certain cancer clones or their microenvironment. Combining laser capture microscopy, low input genomic sequencing and lineage tracing techniques to breast cancer specimens from before and after neoadjuvant chemotherapy we will examine spatial clonal structure in breast cancers and how it changes across treatment. This data will then be integrated with other spatial &amp; omic approaches to provide further insights such as the interaction between different clones and the microenvironment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005336","title":"Breast_clonal_dynamics_across_chemotherapy_WGS","description":"Mapping the clonal landscape in breast cancers across treatment.","abstract":"Cancer arises through a combination of mutation and selection. Chemotherapy can obliterate some cancers but some cancers exhibit treatment resistance whereby some clones continue to grow or new clones emerge. This may reflect intrinsic features of certain cancer clones or their microenvironment. Combining laser capture microscopy, low input genomic sequencing and lineage tracing techniques to breast cancer specimens from before and after neoadjuvant chemotherapy we will examine spatial clonal structure in breast cancers and how it changes across treatment. This data will then be integrated with other spatial &amp; omic approaches to provide further insights such as the interaction between different clones and the microenvironment.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005337","title":"Whole_breast_profiling_WES","description":"Deep genomic profiling of normal and neoplastic tissues to chart the development of the breast and the transition to disease.","abstract":"All tissues continuously acquire mutations. Combining laser capture microscopy, low input genomic sequencing and lineage tracing techniques to 'whole breast' specimens we will chart how the tissue develops over space and time. This data will then be integrated with other omic approaches to provide further insights such as the interaction between different clones and the microenvironment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005338","title":"Breast_CIS_WES","description":"LCM guided multiregion sequencing of breast tissues to examine patterns of cancer progression and growth.","abstract":"To understand the diverse evolutionary trajectories of healthy and cancerous breast tissue cells we are using spatially resolved molecular analyses in normal tissues and breast cancers from the earliest stage of disease (pre-invasive), through to the stages of tissue invasion. Laser capture microscopy and genomic profiling will reveal the extent of genomic diversity in the breast samples studied here. Individual subclones, defined by their genotype will then be mapped in breast tissues in space and time using spatial profiling approaches. Spatial localisation will allow individual subclones to be studied in the context of the histological structure, in relation to localised immune infiltrates and normal tissue responses.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005339","title":"The mutational landscape of primary central nervous system lymphoma (Hipo H050, A050, XD013)","description":"]Primary lymphomas of the central nervous system (PCNSL) are diffuse large B-cell lymphomas (DLBCLs) which are confined to the central nervous system (CNS). Despite extensive research, the molecular alterations leading to PCNSL have not been fully elucidated. In order to provide a comprehensive description of the mutational landscape in PCNSL, we here performed integrative whole genome and transcriptome sequencing analysis of 51 lymphomas presenting in the CNS, including 42 EBV-negative PCNSL, 6 secondary CNS lymphomas (SCNSL) and 3 EBV+ CNSL.","abstract":"]Primary lymphomas of the central nervous system (PCNSL) are diffuse large B-cell lymphomas (DLBCLs) which are confined to the central nervous system (CNS). Despite extensive research, the molecular alterations leading to PCNSL have not been fully elucidated. In order to provide a comprehensive description of the mutational landscape in PCNSL, we here performed integrative whole genome and transcriptome sequencing analysis of 51 lymphomas presenting in the CNS, including 42 EBV-negative PCNSL, 6 secondary CNS lymphomas (SCNSL) and 3 EBV+ CNSL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-28T13:24:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005340","title":"Detection and characterization of lung cancer using cell-free DNA fragmentomes","description":"Lung cancer remains the leading cause of cancer death world-wide, largely due to its late diagnosis.  Non-invasive approaches for assessment of cell-free DNA (cfDNA) provide an opportunity for detection and intervention that may have broader accessibility than current imaging approaches.  Using a machine learning model for detecting tumor-derived cfDNA through genome-wide analyses of cfDNA fragmentation, we examined a prospective study of 365 individuals at risk for lung cancer (Lung Cancer Diagnostic Study, LUCAS), including 129 individuals ultimately diagnosed with lung cancer and 236 individuals determined to not have lung cancer.  We externally validated the cancer detection model using an independent cohort of 385 non-cancer individuals and 46 predominantly early stage lung cancer patients.  Combining fragmentation features with clinical risk factors and CEA levels followed by CT imaging detected 94% of patients with cancer across stages and subtypes, including 91% of stage I/II and 96% of stage III/IV, at 80% specificity.  Genome-wide fragmentation profiles across ~13,000 ASCL1 transcription factor binding sites could be used to distinguish individuals with small cell lung cancer (SCLC) from those with non-small cell lung cancer (NSCLC) with high accuracy (AUC=0.98).  Among individuals with lung cancer, a higher cfDNA fragmentation score was associated with tumor size and invasion, and represented an independent prognostic indicator of survival.  These studies provide a facile approach for non-invasive detection of lung cancer and clinical management of this disease.","abstract":"Lung cancer remains the leading cause of cancer death world-wide, largely due to its late diagnosis.  Non-invasive approaches for assessment of cell-free DNA (cfDNA) provide an opportunity for detection and intervention that may have broader accessibility than current imaging approaches.  Using a machine learning model for detecting tumor-derived cfDNA through genome-wide analyses of cfDNA fragmentation, we examined a prospective study of 365 individuals at risk for lung cancer (Lung Cancer Diagnostic Study, LUCAS), including 129 individuals ultimately diagnosed with lung cancer and 236 individuals determined to not have lung cancer.  We externally validated the cancer detection model using an independent cohort of 385 non-cancer individuals and 46 predominantly early stage lung cancer patients.  Combining fragmentation features with clinical risk factors and CEA levels followed by CT imaging detected 94% of patients with cancer across stages and subtypes, including 91% of stage I/II and 96% of stage III/IV, at 80% specificity.  Genome-wide fragmentation profiles across ~13,000 ASCL1 transcription factor binding sites could be used to distinguish individuals with small cell lung cancer (SCLC) from those with non-small cell lung cancer (NSCLC) with high accuracy (AUC=0.98).  Among individuals with lung cancer, a higher cfDNA fragmentation score was associated with tumor size and invasion, and represented an independent prognostic indicator of survival.  These studies provide a facile approach for non-invasive detection of lung cancer and clinical management of this disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-28T13:53:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005341","title":"WGS Leiomyosarcoma subtypes","description":null,"abstract":"Leiomyosarcomas (LMS) are genetically heterogeneous tumors differentiating along smooth muscle lines. Currently, LMS treatment is not informed by molecular subtyping and is associated with highly variable survival. While disease site continues to dictate clinical management, the contribution of genetic factors to LMS subtype, origins, and timing are unknown. Here we analyzed 70 genomes and 130 transcriptomes of LMS, including multiple tumor regions and paired metastases. Molecular profiling highlighted the extremely early origins of LMS. Three specific subtypes of LMS develop from distinct lineages of smooth muscle cells. Of these, dedifferentiated LMS with high immune infiltration and tumors primarily of gynaecological origin acquired the highest burden of genomic mutation and are associated with worse survival. Homologous recombination defects lead to genome-wide mutational signatures, and a corresponding sensitivity to PARP and other DNA damage response inhibitors, suggesting a novel  therapeutic    strategy for LMS. Finally, by phylogenetic reconstruction, we present evidence that clones seeding lethal metastases arise decades prior to LMS diagnosis.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-28T17:00:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005342","title":"Metabolomic and microbiome profiling reveals personalized risk factors for coronary artery disease","description":"A comprehensive clinical and multi-omic profiling for 199 patients with acute coronary syndrome (ACS), an acute subcategory of CAD, that we recruited in two major Israeli hospitals. We demonstrate that ACS has distinct serum metabolome and gut microbial signatures, as compared to a control cohort. Metabolic aberrations linked with microbiome and diet show a gradual trend with significant metabolite deviations in control participants with metabolic impairment suggesting their involvement in earlier dysmetabolic phases preceding clinically overt CAD.","abstract":"A comprehensive clinical and multi-omic profiling for 199 patients with acute coronary syndrome (ACS), an acute subcategory of CAD, that we recruited in two major Israeli hospitals. We demonstrate that ACS has distinct serum metabolome and gut microbial signatures, as compared to a control cohort. Metabolic aberrations linked with microbiome and diet show a gradual trend with significant metabolite deviations in control participants with metabolic impairment suggesting their involvement in earlier dysmetabolic phases preceding clinically overt CAD.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-05-31T10:24:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005343","title":"Single-cell profiling of neoantigen-specific T cells in lung cancers treated with neoadjuvant PD-1 blockade","description":"We study the expression profile of MANA-specific T cells, we used the MANA functional expansion of specific T cells (MANAFEST) assay in neoadjuvant anti-PD-1-treated lung cancers and applied their T cell receptor’s (TCR) complementarity-determining region 3 (CDR3) as a “barcode” to track and analyze their transcriptional programs in the tumor microenvironment using single cell TCR sequencing coupled with single cell RNA sequencing. We revealed distinct phenotype for MANA- and virus-specific clones in TIL and adjacent normal lung, regardless of response. MANA-specific T cells show features that drive the differences between responders and non-responders.","abstract":"We study the expression profile of MANA-specific T cells, we used the MANA functional expansion of specific T cells (MANAFEST) assay in neoadjuvant anti-PD-1-treated lung cancers and applied their T cell receptor’s (TCR) complementarity-determining region 3 (CDR3) as a “barcode” to track and analyze their transcriptional programs in the tumor microenvironment using single cell TCR sequencing coupled with single cell RNA sequencing. We revealed distinct phenotype for MANA- and virus-specific clones in TIL and adjacent normal lung, regardless of response. MANA-specific T cells show features that drive the differences between responders and non-responders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-01T04:39:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005344","title":"Polyamine metabolism in the human placenta","description":"Polyamine metabolism in the human placenta","abstract":"Polyamine metabolism in the human placenta","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005345","title":"Whole genome sequencing based on short and long reads from GM09237 cell line with and without folate depletion","description":"To asess changes in the DNA-sequence occurring as a result of folate deprivation, DNA extracted from the GM09237 cell line grown with and without folate was sequenced using short read and long read sequencing. The DNA was extracted from cells cultured with either normal medium or medium with no folic acid for 5 days, and then sequenced by BGI PE100 platform (100 bp paired-end sequencing 60x coverage; performed by BGI), or PacBio Sequel system (SMARTbell; performed by BGI) respectively.","abstract":"To asess changes in the DNA-sequence occurring as a result of folate deprivation, DNA extracted from the GM09237 cell line grown with and without folate was sequenced using short read and long read sequencing. The DNA was extracted from cells cultured with either normal medium or medium with no folic acid for 5 days, and then sequenced by BGI PE100 platform (100 bp paired-end sequencing 60x coverage; performed by BGI), or PacBio Sequel system (SMARTbell; performed by BGI) respectively.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-01T12:38:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005346","title":"Novel de novo pathogenic variant in the GNAI1 as a cause of severe disorders of intellectual development with autistic features","description":null,"abstract":"Pathogenic sequence variant in the GNAI1 gene were recently introduced as a cause of novel syndrome with a manifestation of variable developmental delay and autistic features. We report on a case of monozygotic twins with severe intellectual and motor delay and developmental dysphasia. Both probands were examined using multi-step molecular diagnostic algorithm resulting in the identification of a novel, de novo pathogenic sequence variant in the GNAI1 gene, NM_002069.6:c.815A&gt;G, p.(Asn272Gly) with subsequent confirmation of 8q24.23q24.3 duplication and heterozygous 5q13.2 deletion by whole-exome sequencing (WES). Our case confirmed the role of GNAI1 pathogenic sequence variant in the GNAI1 gene in the pathogenesis of neurodevelopmental disorders.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-01T14:22:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005347","title":"An instructive role for IL7RA in the development of human B-cell precursor leukemia","description":"Kinase signaling fuels growth of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Yet its role in leukemia initiation is unclear and has not been shown in primary human hematopoietic cells. We previously described activating mutations in interleukin-7 receptor alpha (IL7RA) in\npoor-prognosis “ph-like” BCP-ALL. Here we show that expression of activated mutant IL7RA in human CD34+ hematopoietic cells creates a preleukemic state in transplanted NOD/LtSz-scid IL2Rγnull mice, characterized by persistence of self-renewing Pro-B cells with non-productive V(D)J gene rearrangements. Preleukemic CD34+CD10highCD19+ cells evolved to a BCP-ALL with spontaneously acquired CDKN2A deletions as commonly observed in primary human BCP-ALL. CRISPR mediated silencing of CDKN2A in primary human CD34+ cells transduced with activated \nIL7RA resulted in robust development of BCP-ALLs in-vivo. Thus, we demonstrate for the first time that constitutive activation of IL7RA can initiate preleukemia in primary human hematopoietic progenitors and cooperates with CDKN2A silencing in progression into BCP-ALL.","abstract":"Kinase signaling fuels growth of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Yet its role in leukemia initiation is unclear and has not been shown in primary human hematopoietic cells. We previously described activating mutations in interleukin-7 receptor alpha (IL7RA) in\npoor-prognosis “ph-like” BCP-ALL. Here we show that expression of activated mutant IL7RA in human CD34+ hematopoietic cells creates a preleukemic state in transplanted NOD/LtSz-scid IL2Rγnull mice, characterized by persistence of self-renewing Pro-B cells with non-productive V(D)J gene rearrangements. Preleukemic CD34+CD10highCD19+ cells evolved to a BCP-ALL with spontaneously acquired CDKN2A deletions as commonly observed in primary human BCP-ALL. CRISPR mediated silencing of CDKN2A in primary human CD34+ cells transduced with activated \nIL7RA resulted in robust development of BCP-ALLs in-vivo. Thus, we demonstrate for the first time that constitutive activation of IL7RA can initiate preleukemia in primary human hematopoietic progenitors and cooperates with CDKN2A silencing in progression into BCP-ALL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-01T17:44:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005348","title":"Integration of metabolomics, genomics and immune phenotypes reveals the causal roles of metabolites in disease","description":null,"abstract":"Background: Recent studies highlight the role of metabolites in immune diseases, but it remains unknown how much of this effect is driven by genetic and non-genetic host factors. \nResult: We systematically investigate circulating metabolites in a cohort of 500 healthy subjects (500FG) in whom immune function and activity are deeply measured and whose genetics are profiled. Our data reveal that several major metabolic pathways, including the alanine/ glutamate pathway and the arachidonic acid pathway, have a strong impact on cytokine production in response to ex vivo stimulation. We also examine genetic regulation of metabolites associated with immune phenotypes through genome-wide association analysis and identify 29 significant loci, including eight novel independent loci. Of these, one locus (rs174584-FADS2) associated with arachidonic acid metabolism is causally associated with Crohn’s disease, suggesting it is a potential therapeutic target.\nConclusion: This study provides a comprehensive map of the integration between the blood metabolome and immune phenotypes, reveals novel genetic factors that regulate blood metabolite concentrations, and proposes an integrative approach for identifying new disease treatment targets.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-01T17:56:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005349","title":"The Xq22.3 contiguous gene deletion syndrome (ATS-ID): from genotype to further delineation of the phenotype","description":null,"abstract":"Alport syndrome with intellectual disability (ATS-ID), also known as AMME complex (OMIM #300194), is an X-linked contiguous gene deletion syndrome associated with an Xq22.3 locus mainly characterized by haematuria, renal failure, hearing loss/deafness, ID/mental retardation (MR), midface hypoplasia and elliptocytosis. . It is thought that ATS-ID is caused by the loss of function of COL4A5 (ATS) and FACL4 (=ACSL4) (ID) through the interstitial (micro)deletion of chromosomal band Xq22.3. We report detailed phenotypic description and results from genome-wide profiling of Czech family with diagnosis ATS-ID (proband, maternal uncle and two female carriers).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005350","title":"Human gut microbiome in babies with biliary atresia and normal controls","description":null,"abstract":"The early onset of disease and the lack of genetic defects in most patients raise the possibility that other prenatal factors influence susceptibility of disease. Here, we test the hypothesis that the composition and function of the intestinal microbiome differs in biliary atresia patients and normal controls.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-01T19:16:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005351","title":"Genomic characterization of co-existing biliary tract intraepithelial neoplasia and carcinoma lesions reveals distinct evolutionary paths of gallbladder cancer","description":null,"abstract":"Gallbladder carcinoma is the most common cancer of the biliary tract with dismal survival largely due to delayed diagnosis. Biliary tract intraepithelial neoplasia (BilIN) is the common benign tumor that is suspected to be precancerous lesions. However, the genetic and evolutionary relationships between BilIN and carcinoma remain unclear. Here we performed whole-exome sequencing of coexisting low-grade BilIN (adenoma), high-grade BilIN, and carcinoma lesions, and normal tissues from the same patients.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005352","title":"Efficacy of CDK4/6i in preclinical models of malignant pleural mesothelioma","description":"Assessment of antitumor activity of CDK4/6 inhibitors using in vitro and in vivo preclinical models of MPM using RNA-sequencing. We also include the genomic characterization (whole exome sequencing) of patient-derived cell lines used in the in vitro experiments.","abstract":"Assessment of antitumor activity of CDK4/6 inhibitors using in vitro and in vivo preclinical models of MPM using RNA-sequencing. We also include the genomic characterization (whole exome sequencing) of patient-derived cell lines used in the in vitro experiments.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-02T08:54:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005353","title":"Single cell RNA-seq reveals immunosuppressive gastric stem-like cancer cells as a poor prognostic factor","description":null,"abstract":"We apply single-cell full-length transcriptome sequencing to analyze 3443 cells from paired normal-adjacent and tumor tissues of 15 gastric cancer patients with different histological profiles. Among the epithelial cells profiled, we discovered subsets of proliferative stem-like cells with upregulated pro-tumor pathways and that were associated with poorer prognosis. Stem-like cell enriched tissues also show distinct T cell populations with proportionally more TIM3+ CD8+ cells, while non-enriched tissues had proportionally more KLRC1+ CD8+ cells, offering opportunities for checkpoint inhibitor therapy. In silico predictions of ligand-receptor interactions revealed immune-suppressive interactions between these stem-like cells and immune cells via interacting pairs such as Nectin-2(CD112)-TIGIT, Galectin-9-TIM3 and CXCL16-CXCR6. Using immunohistochemistry, we found CD8+ T cells expressing TIGIT in close proximity to stem-like cells expressing NECTIN2.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005354","title":"The Xq22.3 contiguous gene deletion syndrome (ATS-ID)","description":null,"abstract":"Alport syndrome with intellectual disability (ATS-ID), also known as AMME complex (OMIM #300194), is an X-linked contiguous gene deletion syndrome associated with an Xq22.3 locus mainly characterized by haematuria, renal failure, hearing loss/deafness, ID/mental retardation (MR), midface hypoplasia and elliptocytosis. . It is thought that ATS-ID is caused by the loss of function of COL4A5 (ATS) and FACL4 (=ACSL4) (ID) through the interstitial (micro)deletion of chromosomal band Xq22.3. We report detailed phenotypic description and results from genome-wide profiling of Czech family with diagnosis ATS-ID (proband, maternal uncle and two female carriers).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-02T14:25:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005355","title":"Novel de novo pathogenic variant in the GNAI1 as a cause of severe disorders of intellectual development with autistic features","description":null,"abstract":"Pathogenic sequence variant in the GNAI1 gene were recently introduced as a cause of novel syndrome with a manifestation of variable developmental delay and autistic features. We report on a case of monozygotic twins with severe intellectual and motor delay and developmental dysphasia. Both probands were examined using multi-step molecular diagnostic algorithm resulting in the identification of a novel, de novo pathogenic sequence variant in the GNAI1 gene, NM_002069.6:c.815A&gt;G, p.(Asn272Gly) with subsequent confirmation of 8q24.23q24.3 duplication and heterozygous 5q13.2 deletion by whole-exome sequencing (WES). Our case confirmed the role of GNAI1 pathogenic sequence variant in the GNAI1 gene in the pathogenesis of neurodevelopmental disorders.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-02T14:48:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005356","title":"Sequential single-cell transcriptional and protein marker profiling reveals TIGIT as a marker of CD19 CAR-T cell dysfunction in patients with non-Hodgkin’s lymphoma","description":"Employed single cell RNA sequencing and protein surface marker profiling of serialCAR-T cell samples from patients with non-Hodgkin’s lymphoma (NHL) to reveal CAR-T cell evolution, identify biomarkers of response, and test for evidence of exhaustion inCAR-T cells of poor responders. At the transcriptional and protein levels, we note the evolution of CAR-T cells toward a non-proliferative, highly-differentiated, andexhausted state that is enriched in CAR-T cells of patients with poor response.Furthermore, we identified the checkpoint receptor TIGIT as a novel prognosticbiomarker and potential driver of CAR-T cell exhaustion.","abstract":"Employed single cell RNA sequencing and protein surface marker profiling of serialCAR-T cell samples from patients with non-Hodgkin’s lymphoma (NHL) to reveal CAR-T cell evolution, identify biomarkers of response, and test for evidence of exhaustion inCAR-T cells of poor responders. At the transcriptional and protein levels, we note the evolution of CAR-T cells toward a non-proliferative, highly-differentiated, andexhausted state that is enriched in CAR-T cells of patients with poor response.Furthermore, we identified the checkpoint receptor TIGIT as a novel prognosticbiomarker and potential driver of CAR-T cell exhaustion.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-02T14:55:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005357","title":"The Xq22.3 contiguous gene deletion syndrome (ATS-ID): from genotype  to further delineation of the phenotype","description":null,"abstract":"Alport syndrome with intellectual disability (ATS-ID), also known as AMME complex (OMIM #300194), is an X-linked contiguous gene deletion syndrome associated with an Xq22.3 locus mainly characterized by haematuria, renal failure, hearing loss/deafness, ID/mental retardation (MR), midface hypoplasia and elliptocytosis. . It is thought that ATS-ID is caused by the loss of function of COL4A5 (ATS) and FACL4 (=ACSL4) (ID) through the interstitial (micro)deletion of chromosomal band Xq22.3. We report detailed phenotypic description and results from genome-wide profiling of Czech family with diagnosis ATS-ID (proband, maternal uncle and two female carriers).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-02T21:11:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005358","title":"Evaluating CRISPR-based Prime Editing for cancer modeling and CFTR repair in organoids","description":null,"abstract":"We evaluate CRISPR-based prime editing for application in organoids. First we model mutations in TP53 in intestinal and hepatocyte oganoids and determine the efficiency and accuracy of mutation induction on multiple targets. Then, to evaluate potential clinical applicability of prime editing we repair mutations in the CFTR channel that cause cystic fibrosis in intestinal organoids. First we repair the CFTR-F508del mutation which is the most common mutation in cystic fibrosis. Then we compare adenine base editing to prime editing by repairing the CFTR-R785* mutation using both strategies.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-03T08:52:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005359","title":"SmMIP-tools:a computational toolset for processing and analysis of single-molecule molecular inversion probes derived data","description":"Single-molecule molecular inversion probes (smMIPs) provides a modular and cost-effective platform for high-multiplex targeted next-generation sequencing (NGS). Nevertheless, translating the raw smMIP-derived sequencing data into accurate and meaningful information currently requires proficient computational skills and a large amount of computational work, prohibiting wide-scale adoption of smMIP-based technologies. To enable easy, efficient, and accurate interrogation of smMIP-derived data, we developed SmMIP-tools, a computational toolset that combines the critical analytic steps for smMIP data interpretation into a single computational pipeline. Here, we describe in detail two major components of the software. The first is a read processing tool that performs quality control steps, generates read-smMIP linkages and retrieves molecular tags. The second is an error-aware variant caller capable of detecting single nucleotide variants (SNVs) and short insertions and deletions (indels). Using a cell-line DNA dilution series and a cohort of blood cancer patients, we benchmarked SmMIP-tools and evaluated its performance against clinical sequencing reports. We anticipate that SmMIP-tools will increase accessibility to smMIP-technology, enabling cost-effective genetic research to push personalized medicine forward.","abstract":"Single-molecule molecular inversion probes (smMIPs) provides a modular and cost-effective platform for high-multiplex targeted next-generation sequencing (NGS). Nevertheless, translating the raw smMIP-derived sequencing data into accurate and meaningful information currently requires proficient computational skills and a large amount of computational work, prohibiting wide-scale adoption of smMIP-based technologies. To enable easy, efficient, and accurate interrogation of smMIP-derived data, we developed SmMIP-tools, a computational toolset that combines the critical analytic steps for smMIP data interpretation into a single computational pipeline. Here, we describe in detail two major components of the software. The first is a read processing tool that performs quality control steps, generates read-smMIP linkages and retrieves molecular tags. The second is an error-aware variant caller capable of detecting single nucleotide variants (SNVs) and short insertions and deletions (indels). Using a cell-line DNA dilution series and a cohort of blood cancer patients, we benchmarked SmMIP-tools and evaluated its performance against clinical sequencing reports. We anticipate that SmMIP-tools will increase accessibility to smMIP-technology, enabling cost-effective genetic research to push personalized medicine forward.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-03T16:59:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005360","title":"The genetic scenario of Mercheros: an under-represented population within the Iberian Peninsula","description":"In this work we analyze for the first time the Merchero population, a Spanish minority ethnic group that has been scarcely studied and historically persecuted. We examine the demographic history and the genetic scenario of Mercheros by using genome-wide array data and whole mitochondrial sequences.","abstract":"In this work we analyze for the first time the Merchero population, a Spanish minority ethnic group that has been scarcely studied and historically persecuted. We examine the demographic history and the genetic scenario of Mercheros by using genome-wide array data and whole mitochondrial sequences.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-03T18:01:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005361","title":"Nucleosome footprinting in plasma cell-free DNA for diagnosis of ovarian cancer","description":"Fragmentation patterns of plasma cell-free DNA (cfDNA) are known to reflect nucleosome positions of cell types contributing to cfDNA. Based on cfDNA fragmentation patterns, the deviation in nucleosome footprints was quantified between diagnosed ovarian cancer patients and healthy individuals.","abstract":"Fragmentation patterns of plasma cell-free DNA (cfDNA) are known to reflect nucleosome positions of cell types contributing to cfDNA. Based on cfDNA fragmentation patterns, the deviation in nucleosome footprints was quantified between diagnosed ovarian cancer patients and healthy individuals.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-04T12:07:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005362","title":"Settlement of Polynesia","description":"Genotypes used to reconstruct the settlement timings and paths of Polynesia.","abstract":"Genotypes used to reconstruct the settlement timings and paths of Polynesia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-04T16:34:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005363","title":"Molecular profiles and urinary biomarkers of upper tract urothelial carcinomas associated with aristolochic acid exposure","description":"This study  present  a  molecular  analysis  of  upper  urinary  tract urothelial  tumours  (UTUC)  and  urines  of  patients  with  past  exposure  to  carcinogenic aristolochic  acid  (AA).  Tumor  exome  and  transcriptome  sequencing  revealed  the  AA-specific  mutations  in  UTUC  and  identified  deleterious  mutations  at  both  the  gene  and transcript  levels.","abstract":"This study  present  a  molecular  analysis  of  upper  urinary  tract urothelial  tumours  (UTUC)  and  urines  of  patients  with  past  exposure  to  carcinogenic aristolochic  acid  (AA).  Tumor  exome  and  transcriptome  sequencing  revealed  the  AA-specific  mutations  in  UTUC  and  identified  deleterious  mutations  at  both  the  gene  and transcript  levels.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-07T08:04:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005364","title":"Mongolia Western HCC","description":"Mongolia has the world’s highest incidence of hepatocellular carcinoma (HCC), with ~100 cases/105 inhabitants. We molecularly characterize the Mongolian (n=192) compared to Western HCCs (n=187) by RNA-seq and WES. Mongolian patients were predominantly younger, female, with HBV-HDV non-cirrhotic livers. Mongolian HCCs had higher rates of protein-coding mutations (121 vs 70 mut /tumor in West), and mutations in known (i.e. APOB) and putative HCC drivers (TSC2). A novel mutational signature (SBS Mongolia) was identified in 25% of cases associated with the carcinogenic DMS genotoxic signature. Two unique molecular classes enriched in HBV-HDV infection, female gender and inflamed tumors are described.","abstract":"Mongolia has the world’s highest incidence of hepatocellular carcinoma (HCC), with ~100 cases/105 inhabitants. We molecularly characterize the Mongolian (n=192) compared to Western HCCs (n=187) by RNA-seq and WES. Mongolian patients were predominantly younger, female, with HBV-HDV non-cirrhotic livers. Mongolian HCCs had higher rates of protein-coding mutations (121 vs 70 mut /tumor in West), and mutations in known (i.e. APOB) and putative HCC drivers (TSC2). A novel mutational signature (SBS Mongolia) was identified in 25% of cases associated with the carcinogenic DMS genotoxic signature. Two unique molecular classes enriched in HBV-HDV infection, female gender and inflamed tumors are described.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-07T08:35:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005365","title":"ChIP sequencing of KMT5B mutant DIPG cells","description":"DIPG are characterised by histone H3K27M mutations, resulting in global loss of the repressive mark H3K27me3, although certain key loci are retained. We recently identified subclonal loss-of-function mutations in the H4 lysine methyltransferase KMT5B to be associated with enhanced invasion/migration, but the mechanism by which this occurred was unclear. Here we use integrated ChIP-seq, ATAC-seq and RNA-seq on patient-derived, subclonal and CRISPR-Cas9-KD DIPG cells to show that loss of KMT5B/C causes depletion of these retained H3K27me3 loci via changes in chromatin accessibility, causing a raft of transcriptional changes which promote tumorigenesis. De-repression occurred at bivalent loci marked by H3K4me3, driving increased transcriptional heterogeneity and elevated gene expression associated with increased invasion, abrogated DNA repair and mesenchymal transition, along with a markedly altered secretome. These data suggest a previously unrecognised trans-histone (H4/H3) interaction in DIPG cells with a potentially profound effect on their diffusely infiltrating phenotype.This datasets comprises ChIP sequencing of H4K20me3, H3K27me3, H3K4me3, H3K9me3 and H4K16ac marks in both naturally occurring and CRISPR engineered KMT5B/C mutant cultured cells from DIPGs.","abstract":"DIPG are characterised by histone H3K27M mutations, resulting in global loss of the repressive mark H3K27me3, although certain key loci are retained. We recently identified subclonal loss-of-function mutations in the H4 lysine methyltransferase KMT5B to be associated with enhanced invasion/migration, but the mechanism by which this occurred was unclear. Here we use integrated ChIP-seq, ATAC-seq and RNA-seq on patient-derived, subclonal and CRISPR-Cas9-KD DIPG cells to show that loss of KMT5B/C causes depletion of these retained H3K27me3 loci via changes in chromatin accessibility, causing a raft of transcriptional changes which promote tumorigenesis. De-repression occurred at bivalent loci marked by H3K4me3, driving increased transcriptional heterogeneity and elevated gene expression associated with increased invasion, abrogated DNA repair and mesenchymal transition, along with a markedly altered secretome. These data suggest a previously unrecognised trans-histone (H4/H3) interaction in DIPG cells with a potentially profound effect on their diffusely infiltrating phenotype.This datasets comprises ChIP sequencing of H4K20me3, H3K27me3, H3K4me3, H3K9me3 and H4K16ac marks in both naturally occurring and CRISPR engineered KMT5B/C mutant cultured cells from DIPGs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005366","title":"Mutational bias in spermatogonia impacts the anatomy of regulatory sites in the human genome","description":"Mutation in the germline is the ultimate source of genetic variation, but little is known about the influence of germline chromatin structure on mutational processes. Using ATAC-seq, we profile the open chromatin landscape of human spermatogonia, the most proliferative cell-type of the germline, identifying transcription factor binding sites (TFBSs) and PRDM9-binding sites, a subset of which will initiate meiotic recombination. We observe an increase in rare structural variant (SV) breakpoints at PRDM9-bound sites, implicating meiotic recombination in the generation of structural variation. Many germline TFBSs, such as NRF, are also associated with increased rates of SV breakpoints, apparently independent of recombination. Singleton short insertions (&gt;=5 bp) are highly enriched at TFBSs, particularly at sites bound by testis active TFs, and their rates correlate with those of structural variant breakpoints. Short insertions often duplicate the TFBS motif, leading to clustering of motif sites near regulatory regions in this male-driven evolutionary process. Increased mutation loads at germline TFBSs disproportionately affect neural enhancers with activity in spermatogonia, potentially altering neurodevelopmental regulatory architecture. Local chromatin structure in spermatogonia is thus pervasive in shaping both evolution and disease.","abstract":"Mutation in the germline is the ultimate source of genetic variation, but little is known about the influence of germline chromatin structure on mutational processes. Using ATAC-seq, we profile the open chromatin landscape of human spermatogonia, the most proliferative cell-type of the germline, identifying transcription factor binding sites (TFBSs) and PRDM9-binding sites, a subset of which will initiate meiotic recombination. We observe an increase in rare structural variant (SV) breakpoints at PRDM9-bound sites, implicating meiotic recombination in the generation of structural variation. Many germline TFBSs, such as NRF, are also associated with increased rates of SV breakpoints, apparently independent of recombination. Singleton short insertions (&gt;=5 bp) are highly enriched at TFBSs, particularly at sites bound by testis active TFs, and their rates correlate with those of structural variant breakpoints. Short insertions often duplicate the TFBS motif, leading to clustering of motif sites near regulatory regions in this male-driven evolutionary process. Increased mutation loads at germline TFBSs disproportionately affect neural enhancers with activity in spermatogonia, potentially altering neurodevelopmental regulatory architecture. Local chromatin structure in spermatogonia is thus pervasive in shaping both evolution and disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-07T15:41:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005367","title":"Whole-genome sequencing of lymphomas in immune-privileged sites","description":null,"abstract":"To characterize the genetic alterations in lymphomas in immune-privileged sites (IP-DLBCLs), we performed whole-genome sequencing (WGS) of 22 primary central nervous system lymphomas (PCNSLs), 8 primary testicular lymphomas (PTLs) and 6 secondary CNS lymphomas.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-08T09:32:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005368","title":"RNA-seq on neuroblastoma PDX model COG-N-519 treated with control miR-1283 and test miR-99b-5p mimics","description":null,"abstract":"COG-N-519 primary neuroblastoma cells were innoculated by subcutaneous injection into NSG mice. When tumours reached a size of 100-200mm3 miRNAs conjugated to nanoparticles were injected intratumourally every 2 days for 1 week. 24 hr after the last injection, snap frozen tumour tissue was harvested for RNA extraction and RNA-seq analysis.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-08T13:15:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005369","title":"Retinal Dystrophy_analysis","description":null,"abstract":"Inherited retinal dystrophies (IRD) are a group of diseases characterized by the loss or dysfunction of photoreceptors and a high genetic and clinical heterogeneity. Currently, over 270 genes have been associated with IRD which makes genetic diagnosis very difficult. The recent advent of next generation sequencing has greatly facilitated the diagnosis process, making possible to provide the patients with accurate genetic counseling in some cases. We studied 92 patients clinically diagnosed with IRD with two different custom -panels.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-08T18:37:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005370","title":"RNAseq from regions of insitu and invasive human mammary ductal disease","description":null,"abstract":"To understand the progression of ductal carcinoma insitu (DCIS), we performed RNAseq on individually laser captured regions of pathology annotated human mammary ducts. We identified and sequenced regions annotated as normal ducts, benign ducts, atypical ducts, DCIS and early stage invasive ductal carcinoma (IDC). Freshly frozen biopsies from 145 patients were used, with 31 patients diagnosed with DCIS and no reports of IDC after more than 10 years since original diagnosis. RAW reads were aligned to GRch38/hg38 using STAR.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-08T20:30:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005371","title":"HCA_Urogenital_Foetal_WSSS_RNA","description":"Characterizing developmental trajectories and immune composition of the urinary tract at single-cell resolution","abstract":"Through development, the fetal bladder and kidney become populated by immune populations originating in nascent haematopoietic organs. These cells reside alongside stromal and epithelial compartments of the tissue, and engage in complex niche interactions. In this project we will use single-cell RNA sequencing, single-cell ATAC sequencing, and spatial genomics methods to develop an integrated model for the spatio-temporal pattern of cell-cell interactions and gene expression programmes determining leukocyte tissue residence and function in the urinary tract during fetal development.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005372","title":"Evidence that ciliary genes contribute to non-syndromic familial tall stature","description":null,"abstract":"Human growth is a complex trait. A considerable number of gene defects have been shown to cause short stature, but there are only few examples of genetic causes of non-syndromic tall stature. Besides rare variants with large effects and common risk alleles with small effect size, oligogenic effects may contribute to this phenotype. Exome sequencing was carried out in a tall male (height 3.5 SDS) and his parents. Filtered damaging variants with high CADD scores were validated by Sanger sequencing in the trio and three other affected and one unaffected family members. Network analysis was carried out to assess links between the candidates, and the transcriptome of murine growth plate was analyzed by microarray as well as RNA Seq. Heterozygous gene variants in CEP104, CROCC, NEK1, TOM1L2 and TSTD2 predicted as damaging were found to be shared between the four tall family members. Three of the five genes (CEP104, CROCC and NEK1) belong to the ciliary gene family. All genes are expressed in mouse growth plate. Pathway and network analysis indicated close functional connections. Together, these data expand the spectrum of genes with a role in linear growth and tall stature phenotypes.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-10T06:45:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005373","title":"Genes___Health_imputed_genotype_dataset","description":"Genes &amp; Health is a cohort of British Bangladeshi and British Pakistani individuals. In the Feb2020 data freeze, 28,022 individuals were genotyped on the Illumina Infinium Global Screening Array v3 chip (with the additional Multi-Disease variants). Imputation was performed using the Michigan Imputation Server with the GenomeAsia pilot reference panel, which contains 1,739 genomes and 642 from them are from South Asian groups. This dataset contains imputed SNPs with imputation accuracy &gt;0.3 and MAF &gt;0.1%.","abstract":"Genes &amp; Health is a community-based study of health and disease in British Bangladeshi and British Pakistani individuals, with linked electronic health record data. It allows for the characterisation of common phenotypes such as type 2 diabetets and cardiovascular disease and the investigation of the genetic artecture of these common diseases in this under-represented population. In this Feb2020 data release, 28,022 individuals were genotyped on the Illumina GSA chip and imputed with the GenomeAsia pilot reference panel.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-10T09:27:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005374","title":"Transcriptome and epigenome characterization of BMP signaling effects on H3.3K27M DIPG","description":null,"abstract":"We profiled transcriptome and epigenome of BMP signaling effects on H3.3K27M DIPG","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-11T08:06:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005375","title":"The effect of influenza vaccination","description":null,"abstract":"Cross-protective effects of certain vaccines against heterologous infections have been reported, and long-term boosting of innate immunity (also termed trained immunity) has been proposed as the underlying mechanism. Here, we investigated the effects of influenza vaccination using several layers of -omics data","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005376","title":"Single-cell RNA sequencing dissects gene-environment interactions on gene expression and regulation in immune cells.","description":"This study aims to dissect gene-environment interactions on gene expression and regulation in immune cells using scRNA-seq data from 120 donors being stimulated with 3 pathogens, for 2 different timepoints. More specifically, we identified context- and cell-type-specific eQTLs and co-expression QTLs in PBMCs.","abstract":"This study aims to dissect gene-environment interactions on gene expression and regulation in immune cells using scRNA-seq data from 120 donors being stimulated with 3 pathogens, for 2 different timepoints. More specifically, we identified context- and cell-type-specific eQTLs and co-expression QTLs in PBMCs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-11T08:56:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005377","title":"Spatiotemporal single cell transcriptomic analysis of human gut macrophages reveals multiple functional and niche-specific subsets","description":null,"abstract":"Colonic resections were obtained from patients operated for sigmoid colon cancer at Akershus University Hospital (Ahus, 1478 Lørenskog, Norway). The resected colon was immediately examined by an experienced pathologistand macroscopically normal colon, at least 10 cm from the tumor, were placed in vials with RPMI 1640 and put on ice for transport. The study was performed in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants, and the study was approved by the Regional Committee for Medical Research Ethics (REK, 2018/703, Health Region South-East, Norway). For scRNA-seq, 4 colon specimens from sigmoid or ascending colon were obtained (age 62-78, 3 males). Immunofluorescence stainings were done on samples from 8 patients (age 62-78, 4 males) from ascending, transverse, descending and sigmoid colon. None of the patients had autoimmune, infectious or inflammatory diseases, nor received neoadjuvant chemotherapy or radiation therapy before the operation. All patients were operated following the national guidelines.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-11T09:15:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005378","title":"Placental microRNA sequencing data from human placenta","description":null,"abstract":"miRSeq dataset includes 52 human placentas representing samples from three trimesters. 5 first trimester, 7 second trimester and 40 term samples. Term samples consist of 5 groups (n=8 samples in the group) of normal pregnancy, and cases of late-onset preeclampsia (LO-PE), gestational diabetes (GD), small-and large-for-gestational-age newborns (SGA, LGA) at term.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-11T09:38:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005379","title":"SG Peranakan Project: Genetic admixture in the culturally unique Peranakan Chinese population in Southeast Asia","description":"The Peranakan Chinese are culturally unique descendants of immigrants from China who settled in the Malay Archipelago ~300-500 years ago. Today, among large communities in Southeast Asia, the Peranakans have preserved Chinese traditions with strong influence from the local indigenous Malays. Yet, whether or to what extent genetic admixture co-occurred with the cultural mixture has been a topic of ongoing debate. We performed whole-genome sequencing (WGS) on 177 Singapore (SG) Peranakans and analyzed the data jointly with WGS data of Asian and European populations. We estimated that Peranakan Chinese inherited ~5.62% (95% confidence interval [CI]: 4.75-6.46%) Malay ancestry, much higher than that in SG Chinese (1.08%, 0.69-1.53%), southern Chinese (0.86%, 0.57-1.31%), and northern Chinese (0.25%, 0.18-0.33%). A sex-biased admixture history, in which the Malay ancestry was contributed primarily by females, was supported by X chromosomal variants, and mitochondrial (MT) and Y haplogroups. Finally, we identified an ancient admixture event shared by Peranakan Chinese and SG Chinese ~1,612 (95% CI: 1,345-1,923) years ago, coinciding with the settlement history of Han Chinese in southern China, apart from the recent admixture event with Malays unique to Peranakan Chinese ~190 (159-213) years ago. These findings greatly advance our understanding of the dispersal history of Chinese and their interaction with indigenous populations in Southeast Asia.","abstract":"The Peranakan Chinese are culturally unique descendants of immigrants from China who settled in the Malay Archipelago ~300-500 years ago. Today, among large communities in Southeast Asia, the Peranakans have preserved Chinese traditions with strong influence from the local indigenous Malays. Yet, whether or to what extent genetic admixture co-occurred with the cultural mixture has been a topic of ongoing debate. We performed whole-genome sequencing (WGS) on 177 Singapore (SG) Peranakans and analyzed the data jointly with WGS data of Asian and European populations. We estimated that Peranakan Chinese inherited ~5.62% (95% confidence interval [CI]: 4.75-6.46%) Malay ancestry, much higher than that in SG Chinese (1.08%, 0.69-1.53%), southern Chinese (0.86%, 0.57-1.31%), and northern Chinese (0.25%, 0.18-0.33%). A sex-biased admixture history, in which the Malay ancestry was contributed primarily by females, was supported by X chromosomal variants, and mitochondrial (MT) and Y haplogroups. Finally, we identified an ancient admixture event shared by Peranakan Chinese and SG Chinese ~1,612 (95% CI: 1,345-1,923) years ago, coinciding with the settlement history of Han Chinese in southern China, apart from the recent admixture event with Malays unique to Peranakan Chinese ~190 (159-213) years ago. These findings greatly advance our understanding of the dispersal history of Chinese and their interaction with indigenous populations in Southeast Asia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-11T15:07:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005380","title":"An analysis of humoral and cellular immune responses following COVID-19 vaccination.","description":"Two dose mRNA vaccination provides excellent protection against SARS-CoV-2.  However, there are few data on vaccine efficacy in elderly individuals above the age of 801. Additionally, new variants of concern (VOC) with reduced sensitivity to neutralising antibodies have raised fears for vulnerable groups. Here we assessed humoral and cellular immune responses following vaccination with mRNA vaccine BNT162b22 in elderly participants prospectively recruited from the community and younger health care workers. Median age was 72 years and 51% were females amongst 140 participants. Neutralising antibody responses after the first vaccine dose diminished with increasing age, with a steep drop in participants over 80 years old. Sera from participants below and above 80 showed significantly lower neutralisation potency against B.1.1.7, B.1.351 and P.1. variants of concern as compared to wild type. Those over 80 were more likely to lack any neutralisation against VOC compared younger participants following first dose. Binding IgG and IgA antibodies were lower in the elderly, as was the frequency of SARS-CoV-2 Spike specific B- cells. We observed a trend towards lower somatic hypermutation in participants with suboptimal neutralisation, and elderly participants demonstrated clear reduction in class switched somatic hypermutation, driven by the IgA1/2 isotype. SARS-CoV-2 Spike specific T- cell IFN?? and IL-2 responses were secreted primarily by CD4 T cells, and impaired in the older age group. We conclude that the elderly are a high risk population that warrant specific measures in order to mitigate against vaccine failure, particularly where variants of concern are circulating. Specifically, the dosing interval should not be extended in this group.","abstract":"Two dose mRNA vaccination provides excellent protection against SARS-CoV-2.  However, there are few data on vaccine efficacy in elderly individuals above the age of 801. Additionally, new variants of concern (VOC) with reduced sensitivity to neutralising antibodies have raised fears for vulnerable groups. Here we assessed humoral and cellular immune responses following vaccination with mRNA vaccine BNT162b22 in elderly participants prospectively recruited from the community and younger health care workers. Median age was 72 years and 51% were females amongst 140 participants. Neutralising antibody responses after the first vaccine dose diminished with increasing age, with a steep drop in participants over 80 years old. Sera from participants below and above 80 showed significantly lower neutralisation potency against B.1.1.7, B.1.351 and P.1. variants of concern as compared to wild type. Those over 80 were more likely to lack any neutralisation against VOC compared younger participants following first dose. Binding IgG and IgA antibodies were lower in the elderly, as was the frequency of SARS-CoV-2 Spike specific B- cells. We observed a trend towards lower somatic hypermutation in participants with suboptimal neutralisation, and elderly participants demonstrated clear reduction in class switched somatic hypermutation, driven by the IgA1/2 isotype. SARS-CoV-2 Spike specific T- cell IFN?? and IL-2 responses were secreted primarily by CD4 T cells, and impaired in the older age group. We conclude that the elderly are a high risk population that warrant specific measures in order to mitigate against vaccine failure, particularly where variants of concern are circulating. Specifically, the dosing interval should not be extended in this group.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-11T16:13:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005381","title":"re-upload","description":"For re-upload","abstract":"For re-upload","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005382","title":"Single cell copy number and chromatin accessibility in primary multiple myeloma cells","description":"Multiple myeloma is characterized by inter- and intra-clonal heterogeneity. We have used single cell profiling of the genome (scCNV) and epigenome (csATAC) of clonal plasma cells to delineate the clonal heterogeneity in serially collected samples.","abstract":"Multiple myeloma is characterized by inter- and intra-clonal heterogeneity. We have used single cell profiling of the genome (scCNV) and epigenome (csATAC) of clonal plasma cells to delineate the clonal heterogeneity in serially collected samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-11T22:38:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005383","title":"SORL1 FAMILY","description":null,"abstract":"Whole exome sequencing and linkage analysis were performed in a three generational pedigree of Greek origin with a broad phenotypic spectrum spanning from Parkinson’s disease and Parkinson’s disease dementia to dementia of mixed type (Alzheimer disease and vascular dementia). \nWe identified a novel heterozygous c.G1135T (p.G379W) variant in SORL1 which segregated with the disease in the family. Mutation screening in sporadic Greek PD cases identified one additional individual with the mutation, sharing the same 12.8Mb haplotype.\n Our findings provide support for SORL1 mutations resulting in a broad range of additional phenotypes and warrants further studies in neurodegenerative diseases beyond AD.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005384","title":"Mutational impact in liver stem cells under precancerous alcoholic liver, NASH and PSC disease conditions","description":null,"abstract":"Inflammatory liver disease increases risk of developing liver cancer. The mechanism through which liver disease induces tumorigenesis remains unclear, but is thought to occur via increased mutagenesis. Here, we performed whole-genome sequencing on clonal stem cell organoid lines derived from explanted diseased liver cells from patients with chronic alcohol consumption, non-alcoholic steatohepatitis NASH, and primary sclerosing cholangitis PSC. Surprisingly, we find that these precancerous liver disease conditions do not result in a detectable increased accumulation of mutations, nor altered mutation types in normal stem cells in the liver, which contrasts with typical mutational signatures found in liver tumors. Our findings argue against the idea that liver disease drives tumorigenesis via a direct mechanism of induced mutagenesis, and suggests that the transition from healthy to cancerous liver cells likely occurs through other mechanisms, such as changes to the microenvironment that facilitate the outgrowth of precancerous cells that would normally be suppressed. Increased proliferation of such cells would result in an increase in mutations associated with endogenous mutational processes, which we indeed observed when examining the early stage mutations in a hepatocellular carcinoma.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-14T12:19:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005385","title":"An integrative model of pathway convergence in genetically heterogeneous blast crisis chronic myeloid leukemia (CML)","description":null,"abstract":"Targeted therapies against the BCR-ABL1 kinase have revolutionized treatment of chronic phase (CP) chronic myeloid leukemia (CML). In contrast, management of blast crisis (BC) CML remains challenging because BC cells acquire complex molecular alterations that confer stemness features to progenitor populations and resistance to BCR-ABL1 tyrosine kinase inhibitors. Comprehensive models of BC transformation have proved elusive because of the rarity and genetic heterogeneity of BC, but are important for developing biomarkers predicting BC progression and effective therapies. To better understand BC, we performed an integrated multiomics analysis of 74 CP and BC samples using whole-genome and exome sequencing, transcriptome and methylome profiling, and chromatin immunoprecipitation followed by high-throughput sequencing. Employing pathway-based analysis, we found the BC genome was significantly enriched for mutations affecting components of the polycomb repressive complex (PRC) pathway. While transcriptomically, BC progenitors were enriched and depleted for PRC1- and PRC2-related gene sets respectively. By integrating our data sets, we determined that BC progenitors undergo PRC-driven epigenetic reprogramming toward a convergent transcriptomic state. Specifically, PRC2 directs BC DNA hypermethylation, which in turn silences key genes involved in myeloid differentiation and tumor suppressor function via so-called epigenetic switching, whereas PRC1 represses an overlapping and distinct set of genes, including novel BC tumor suppressors. On the basis of these observations, we developed an integrated model of BC that facilitated the identification of combinatorial therapies capable of reversing BC reprogramming (decitabine+PRC1 inhibitors), novel PRC-silenced tumor suppressor genes (NR4A2), and gene expression signatures predictive of disease progression and drug resistance in CP.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005386","title":"An integrative model of pathway convergence in genetically heterogeneous blast crisis chronic myeloid leukemia (CML)","description":null,"abstract":"Targeted therapies against the BCR-ABL1 kinase have revolutionized treatment of chronic phase (CP) chronic myeloid leukemia (CML). In contrast, management of blast crisis (BC) CML remains challenging because BC cells acquire complex molecular alterations that confer stemness features to progenitor populations and resistance to BCR-ABL1 tyrosine kinase inhibitors. Comprehensive models of BC transformation have proved elusive because of the rarity and genetic heterogeneity of BC, but are important for developing biomarkers predicting BC progression and effective therapies. To better understand BC, we performed an integrated multiomics analysis of 74 CP and BC samples using whole-genome and exome sequencing, transcriptome and methylome profiling, and chromatin immunoprecipitation followed by high-throughput sequencing. Employing pathway-based analysis, we found the BC genome was significantly enriched for mutations affecting components of the polycomb repressive complex (PRC) pathway. While transcriptomically, BC progenitors were enriched and depleted for PRC1- and PRC2-related gene sets respectively. By integrating our data sets, we determined that BC progenitors undergo PRC-driven epigenetic reprogramming toward a convergent transcriptomic state. Specifically, PRC2 directs BC DNA hypermethylation, which in turn silences key genes involved in myeloid differentiation and tumor suppressor function via so-called epigenetic switching, whereas PRC1 represses an overlapping and distinct set of genes, including novel BC tumor suppressors. On the basis of these observations, we developed an integrated model of BC that facilitated the identification of combinatorial therapies capable of reversing BC reprogramming (decitabine+PRC1 inhibitors), novel PRC-silenced tumor suppressor genes (NR4A2), and gene expression signatures predictive of disease progression and drug resistance in CP.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005387","title":"Alveolar Rhabdomyosarcoma sequencing data","description":"This study shares DNA and RNA sequencing data from alveolar rhadbomyosarcoma patients","abstract":"This study shares DNA and RNA sequencing data from alveolar rhadbomyosarcoma patients","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-14T17:35:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005388","title":"phylogenetic lineage tracing from single hematopoietic cells of two humans","description":null,"abstract":"This study is a proof-of-concept for the phylogenetic reconstruction from single cell DNA sequencing data of human cells, isolated from peripheral blood from two donors. One of the donors has an MSH6- mismatch repair deficiency, resulting in a higher mutation rate that increases the amount phylogenetic signal through increased somatic variation. The analysis in the study uses a dedicated variation caller for single cell DNA sequencing data, ProSolo, which leverages a bulk background sample to deal with amplification-induced errors and biases. The phylogenetic reconstruction is done with RAxML-NG, a maximum likelihood approach that can model diploid genotypes and handle ProSolo's fine-grained posterior probabilities for such genotypes.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005389","title":"Integrative Profiling of T790M Negative EGFR Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities","description":"We performed whole exome and transcriptome analysis of 59 first- and second-generation EGFR TKI resistant metastatic EGFR mutated patients to characterize and compare molecular alterations mediating resistance in T790M positive and negative disease. Transcriptomic analysis revealed ubiquitous loss of adenocarcinoma lineage gene expression in T790M negative tumors, orthogonally validated using multiplex immunohistochemistry. There was enrichment of genomic features such as TP53 alterations, 3q chromosomal amplifications, whole genome doubling and non-aging mutational signatures in T790M negative tumors. Almost half of resistant tumors were further classified as Immunehot, with clinical outcomes conditional on immune cell infiltration state and T790M status. Finally, using a Bayesian statistical approach, we explored how T790M negative and positive disease might be predicted using comprehensive genomic and transcriptomic profiles of treatment-naïve patients.","abstract":"We performed whole exome and transcriptome analysis of 59 first- and second-generation EGFR TKI resistant metastatic EGFR mutated patients to characterize and compare molecular alterations mediating resistance in T790M positive and negative disease. Transcriptomic analysis revealed ubiquitous loss of adenocarcinoma lineage gene expression in T790M negative tumors, orthogonally validated using multiplex immunohistochemistry. There was enrichment of genomic features such as TP53 alterations, 3q chromosomal amplifications, whole genome doubling and non-aging mutational signatures in T790M negative tumors. Almost half of resistant tumors were further classified as Immunehot, with clinical outcomes conditional on immune cell infiltration state and T790M status. Finally, using a Bayesian statistical approach, we explored how T790M negative and positive disease might be predicted using comprehensive genomic and transcriptomic profiles of treatment-naïve patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-15T10:05:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005390","title":"Next Generation Children project - Whole Genome Sequencing study for patients in PICU","description":"Here we describe our rapid method to sequence sick patients and attempt to diagnose any genetic aetiology associated with the sickness","abstract":"Here we describe our rapid method to sequence sick patients and attempt to diagnose any genetic aetiology associated with the sickness","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005391","title":"HCA_Heart_Foetal_BHF_DZHK_RNA","description":"Cell Atlas of the Foetal Heart","abstract":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess human development. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005392","title":"Evaluation of the immune effects of tumor-treating electric fields (TTFields) in GBM patients","description":null,"abstract":"Transcriptomic analysis of glioblastoma (GBM) patients’ samples before and after treatment either with standard chemoradiation (TMZ+RT)  or chemoradiation + TTFields (Novocure) 200 kHz. The original study (Diamant et al J Immunol 2021) evaluated changes in immune signature and immune infiltrate as evaluated by immune cell signatures.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-16T13:12:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005393","title":"Papua New Guinean Genome Diversity Project","description":"Papua New Guinean populations have one of the highest genetic diversity of the world. Our dataset provides genomic data covering most of the Papua New Guinean territory (n=58).","abstract":"Papua New Guinean populations have one of the highest genetic diversity of the world. Our dataset provides genomic data covering most of the Papua New Guinean territory (n=58).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-16T14:22:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005394","title":"Functional dissection of inherited non-coding variation influencing multiple myeloma risk","description":"The project aimed at identification of genotype dependent chromatin accessibility in MM patients.","abstract":"The project aimed at identification of genotype dependent chromatin accessibility in MM patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-16T16:15:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005395","title":"Analysis of RAD51C promoter methylation using targeted bisulfite sequencing (amplicon sequencing) in ovarian cancer pre-clinical models and patient samples.","description":"In high-grade serous ovarian carcinoma (HGSC), deleterious mutations in the DNA repair gene RAD51C are established drivers of defective homologous recombination and are emerging biomarkers of PARP inhibitor (PARPi) sensitivity. RAD51C promoter methylation (meRAD51C) is detected at similar frequencies to mutations, yet its effects on PARPi responses remain unresolved. In this study, three HGSC patient-derived xenograft (PDX) models with methylation at most or all examined CpG sites in the RAD51C promoter show responses to PARPi. Both complete and heterogeneous methylation patterns were associated with RAD51C gene silencing and homologous recombination deficiency (HRD). PDX models lost meRAD51C following treatment with PARPi rucaparib or niraparib, where a single unmethylated copy of RAD51C was sufficient to drive PARPi resistance. Genomic copy number profiling of one of the PDX models using SNP arrays revealed that this resistance was acquired independently in two genetically distinct lineages. In a cohort of 11 patients with RAD51C-methylated HGSC, various patterns of meRAD51C were associated with genomic 'scarring', indicative of HRD history, but exhibited no clear correlations with clinical outcome. Differences in methylation stability under treatment pressure were also observed between patients, where one HGSC was found to maintain meRAD51C after 6 lines of therapy (4 platinum-based), whilst another HGSC sample was found to have heterozygous meRAD51C and elevated RAD51C gene expression (relative to homozygous meRAD51C controls) after only neo-adjuvant chemotherapy. As meRAD51C loss in a single gene copy was sufficient to cause PARPi resistance in PDX, methylation zygosity should be carefully assessed in previously treated patients when considering PARPi therapy.","abstract":"In high-grade serous ovarian carcinoma (HGSC), deleterious mutations in the DNA repair gene RAD51C are established drivers of defective homologous recombination and are emerging biomarkers of PARP inhibitor (PARPi) sensitivity. RAD51C promoter methylation (meRAD51C) is detected at similar frequencies to mutations, yet its effects on PARPi responses remain unresolved. In this study, three HGSC patient-derived xenograft (PDX) models with methylation at most or all examined CpG sites in the RAD51C promoter show responses to PARPi. Both complete and heterogeneous methylation patterns were associated with RAD51C gene silencing and homologous recombination deficiency (HRD). PDX models lost meRAD51C following treatment with PARPi rucaparib or niraparib, where a single unmethylated copy of RAD51C was sufficient to drive PARPi resistance. Genomic copy number profiling of one of the PDX models using SNP arrays revealed that this resistance was acquired independently in two genetically distinct lineages. In a cohort of 11 patients with RAD51C-methylated HGSC, various patterns of meRAD51C were associated with genomic 'scarring', indicative of HRD history, but exhibited no clear correlations with clinical outcome. Differences in methylation stability under treatment pressure were also observed between patients, where one HGSC was found to maintain meRAD51C after 6 lines of therapy (4 platinum-based), whilst another HGSC sample was found to have heterozygous meRAD51C and elevated RAD51C gene expression (relative to homozygous meRAD51C controls) after only neo-adjuvant chemotherapy. As meRAD51C loss in a single gene copy was sufficient to cause PARPi resistance in PDX, methylation zygosity should be carefully assessed in previously treated patients when considering PARPi therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-17T05:27:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005396","title":"Interferon lambda 4 impairs viral antigen presentation and attenuates T cell responses","description":"Genetic variants of the interferon lambda (IFNL) gene locus are strongly associated with spontaneous and IFN treatment induced clearance of hepatitis C virus (HCV) infections. Individuals with the ancestral IFNL4-dG allele are not able to clear HCV in the acute phase and develop chronic hepatitis C (CHC) with more than 90% probability. Paradoxically, the IFNL4-dG allele encodes a fully functional IFNλ4 protein with antiviral activity against HCV and coronavirus. Here we describe a hitherto unknown effect of IFNλ4 on HCV antigen presentation. Only minor amounts of IFNλ4 are secreted, because the protein is largely retained in the endoplasmic reticulum (ER) where it induces ER stress. Stressed cells were significantly weaker activators of HCV specific CD8+ T cells. This was not due to reduced MHC I surface presentation or extracellular IFNλ4 effects, since T cell responses could be restored by exogenous loading of MHC with HCV antigens. Rather, IFNλ4 induced ER stress impaired HCV antigen processing and/or loading onto the MHC I complex. Our results provide a potential explanation for the IFNλ4 – HCV paradox.","abstract":"Genetic variants of the interferon lambda (IFNL) gene locus are strongly associated with spontaneous and IFN treatment induced clearance of hepatitis C virus (HCV) infections. Individuals with the ancestral IFNL4-dG allele are not able to clear HCV in the acute phase and develop chronic hepatitis C (CHC) with more than 90% probability. Paradoxically, the IFNL4-dG allele encodes a fully functional IFNλ4 protein with antiviral activity against HCV and coronavirus. Here we describe a hitherto unknown effect of IFNλ4 on HCV antigen presentation. Only minor amounts of IFNλ4 are secreted, because the protein is largely retained in the endoplasmic reticulum (ER) where it induces ER stress. Stressed cells were significantly weaker activators of HCV specific CD8+ T cells. This was not due to reduced MHC I surface presentation or extracellular IFNλ4 effects, since T cell responses could be restored by exogenous loading of MHC with HCV antigens. Rather, IFNλ4 induced ER stress impaired HCV antigen processing and/or loading onto the MHC I complex. Our results provide a potential explanation for the IFNλ4 – HCV paradox.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-17T11:22:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005397","title":"__HCA_Brain_Paediatric_Bayraktar_RNA_","description":"Characterising the human microglia response to acute brain injury within paediatric samples.","abstract":"Using single nuclei techniques to characterise the human microglia response to acute brain injury within paediatric samples.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005398","title":"Prevalence of transthyretin amyloidosis in patients with heart failure and no left ventricular hypertrophy","description":"The study prospectively enrolled patients admitted for HF with LV ejection fraction (LVEF) ≥ 50% and LV wall thickness &lt;12 mm. TTR cardiac amyloidosis was diagnosed according to accepted criteria, which include positive cardiac 99-Tc-DPD scintigraphy in the absence of monoclonal protein expansion in blood. In a cohort of patients with HFpEF without LVH, the prevalence of TTR cardiac amyloidosis was 5%. Transthyretin gene sequencing was performed in positive patients.","abstract":"The study prospectively enrolled patients admitted for HF with LV ejection fraction (LVEF) ≥ 50% and LV wall thickness &lt;12 mm. TTR cardiac amyloidosis was diagnosed according to accepted criteria, which include positive cardiac 99-Tc-DPD scintigraphy in the absence of monoclonal protein expansion in blood. In a cohort of patients with HFpEF without LVH, the prevalence of TTR cardiac amyloidosis was 5%. Transthyretin gene sequencing was performed in positive patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-17T15:31:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005399","title":"PELICAN33 longitudinal clinical and autopsy phenomic assessment in lethal metastatic prostate cancer","description":"Objective: To identify novel phenotypes and features associated with metastatic prostate cancer (mPC) outcome, and to identify biomarker and data requirements to be tested in future precision oncology trials.\n\nDesign, Setting, and Participants: We analyzed deep longitudinal clinical, neuroendocrine expression, and autopsy data of 33 men who died from mPC between 1995 and 2004 (PELICAN33), and related findings to mPC biomarkers reported in the literature.\n\nIntervention: 33 men prospectively consented to participate in an integrated clinical-molecular rapid autopsy study of mPC.","abstract":"Objective: To identify novel phenotypes and features associated with metastatic prostate cancer (mPC) outcome, and to identify biomarker and data requirements to be tested in future precision oncology trials.\n\nDesign, Setting, and Participants: We analyzed deep longitudinal clinical, neuroendocrine expression, and autopsy data of 33 men who died from mPC between 1995 and 2004 (PELICAN33), and related findings to mPC biomarkers reported in the literature.\n\nIntervention: 33 men prospectively consented to participate in an integrated clinical-molecular rapid autopsy study of mPC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-17T17:40:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005400","title":"The tissue origin of highly elevated cell-free DNA in patients with and without cancer","description":"Forty years ago, the first measurements of cell free DNA (cfDNA) from cancer patients revealed that its total concentration was often elevated compared to healthy controls. The basis for this increase, and in particular the source of the extra cfDNA in such patients, has never been determined. To address this issue, we assessed methylation patterns of cfDNA from 57 individuals, 34 of whom had unequivocally elevated cfDNA concentrations (i.e., &gt;15 ng/mL of plasma). We found that the excess cfDNA in cancer patients did not come from either neoplastic cells or surrounding cells from the tumor's tissue of origin. Instead, 80% of the cfDNA was derived from neutrophils, B cells or T cells, with neutrophils accounting for ~2/3. B cells contributed more than T cells despite the great excess of T cells over B cells in the blood. To see if this result was generalizable to other clinical situations in which elevated cfDNA concentrations have been described, we evaluated nine patients before and one day following surgery. After surgical resection, cfDNA concentration increased by an average of 16.1-fold, as expected. The majority of this increase (55%) was contributed by leukocytes, though damaged hepatocytes contributed a substantial minority (31% of increase). These data suggest that the elevated concentrations of cfDNA in cancer patients, as with patients after surgery, arises largely from dying leukocytes—not from the neoplastic cells or the tissue of origin of the cancer.","abstract":"Forty years ago, the first measurements of cell free DNA (cfDNA) from cancer patients revealed that its total concentration was often elevated compared to healthy controls. The basis for this increase, and in particular the source of the extra cfDNA in such patients, has never been determined. To address this issue, we assessed methylation patterns of cfDNA from 57 individuals, 34 of whom had unequivocally elevated cfDNA concentrations (i.e., &gt;15 ng/mL of plasma). We found that the excess cfDNA in cancer patients did not come from either neoplastic cells or surrounding cells from the tumor's tissue of origin. Instead, 80% of the cfDNA was derived from neutrophils, B cells or T cells, with neutrophils accounting for ~2/3. B cells contributed more than T cells despite the great excess of T cells over B cells in the blood. To see if this result was generalizable to other clinical situations in which elevated cfDNA concentrations have been described, we evaluated nine patients before and one day following surgery. After surgical resection, cfDNA concentration increased by an average of 16.1-fold, as expected. The majority of this increase (55%) was contributed by leukocytes, though damaged hepatocytes contributed a substantial minority (31% of increase). These data suggest that the elevated concentrations of cfDNA in cancer patients, as with patients after surgery, arises largely from dying leukocytes—not from the neoplastic cells or the tissue of origin of the cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005401","title":"Single-cell genome-wide concurrent haplotyping and copy-number profiling through genotyping-by-sequencing","description":null,"abstract":"scGBS is a single-cell sequencing-based methodology to haplotype and copy-number profile single cells. Genomic size and complexity is reduced through restriction enzyme digestion and DNA is genotyped through sequencing of the restriction fragments. scGBS data serves as the input for haplarithmisis, an algorithm we previously developed for SNP array-based single-cell haplotyping. We established technical parameters and developed an analysis pipeline enabling accurate concurrent haplotyping and copy-number profiling of single cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-18T11:26:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005402","title":"Genomic characterization of co-existing biliary tract intraepithelial neoplasia and carcinoma lesions reveals distinct evolutionary paths of gallbladder cancer","description":"Gallbladder carcinoma is the most common cancer of the biliary tract with dismal survival largely due to delayed diagnosis. Biliary tract intraepithelial neoplasia (BilIN) is the common benign tumor that is suspected to be precancerous lesions. However, the genetic and evolutionary relationships between BilIN and carcinoma remain unclear. Here we performed whole-exome sequencing of coexisting low-grade BilIN (adenoma), high-grade BilIN, and carcinoma lesions, and normal tissues from the same patients.","abstract":"Gallbladder carcinoma is the most common cancer of the biliary tract with dismal survival largely due to delayed diagnosis. Biliary tract intraepithelial neoplasia (BilIN) is the common benign tumor that is suspected to be precancerous lesions. However, the genetic and evolutionary relationships between BilIN and carcinoma remain unclear. Here we performed whole-exome sequencing of coexisting low-grade BilIN (adenoma), high-grade BilIN, and carcinoma lesions, and normal tissues from the same patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-21T08:14:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005403","title":"Germline RUNX1 Variation and Predisposition to Childhood Acute Lymphoblastic","description":"Somatic mutations of RUNX1, which encodes the myeloid and lymphoid transcriptional factor RUNX1, are common in both B- and T- acute lymphoid leukemia (ALL) and are associated with poor prognosis of T-ALL. However, there has been no comprehensive investigation of the pattern or prevalence of RUNX1 germline mutation in both B- and T-ALL. Here we report germline RUNX1 variants in 1.23% of B-ALL and 2.11% of T-ALL, identifying 31 unique variants in 62 B-ALL and 18 unique variants in 26 T-ALL children. The majority of frameshift and nonsense variants affected RUNX1 function in transcriptional regulation, hematopoiesis, and cellular proliferation. We identified JAK3 as the most frequent somatic mutation in T-ALL with RUNX1 variants. These results not only identify RUNX1 as a leukemia predisposition gene but also further underline the importance of germline genetic variants to the development of ALL","abstract":"Somatic mutations of RUNX1, which encodes the myeloid and lymphoid transcriptional factor RUNX1, are common in both B- and T- acute lymphoid leukemia (ALL) and are associated with poor prognosis of T-ALL. However, there has been no comprehensive investigation of the pattern or prevalence of RUNX1 germline mutation in both B- and T-ALL. Here we report germline RUNX1 variants in 1.23% of B-ALL and 2.11% of T-ALL, identifying 31 unique variants in 62 B-ALL and 18 unique variants in 26 T-ALL children. The majority of frameshift and nonsense variants affected RUNX1 function in transcriptional regulation, hematopoiesis, and cellular proliferation. We identified JAK3 as the most frequent somatic mutation in T-ALL with RUNX1 variants. These results not only identify RUNX1 as a leukemia predisposition gene but also further underline the importance of germline genetic variants to the development of ALL","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-21T16:17:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005404","title":"HCA_Skin_Adult_WSSS_Spatial_KCL","description":"WSSS spatial transcriptomic analysis healthy human adult skin. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"WSSS Deep Dive Healthy human adult skin: The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005405","title":"Identifying transcriptional programs underlying anti-EGFR small molecule response and resistance with TraCe-seq","description":"Genetic and non-genetic heterogeneity within cancer cell populations represents a major challenge to anti-cancer therapies. We currently lack robust methods to determine how pre-existing and adaptive features affect cellular responses to therapies. Here, by conducting clonal fitness mapping and transcriptional characterization using expressed barcodes and single-cell RNA-sequencing, we have developed TraCe-seq, a method that captures at clonal resolution the origin, fate, and differential early adaptive transcriptional programs of cells in a complex population in response to distinct treatments. We used TraCe-seq to benchmark how next-generation dual EGFR inhibitors-degraders compare to standard EGFR kinase inhibitors in EGFR-mutant lung cancer cells.\nTo QC the TraCe-seq strategy, single-cell RNA-seq libraries were generated from a variety of human cancer cell lines transduced with the TraCe-seq library to validate the TraCe-seq strategy. Specifically, 5 different cell lines (PC9, MCF-10A, MDA-MB-231, NCI-H358, and NCI-H1373) were each transduced with a unique TraCe-seq barcode. The transduced cells were selected with puromycin only, dissociated to single cell suspensions, and then mixed together. The complex mixture of the 5 cell lines was profiled by 10X scRNA-seq. Furthermore, transduced NCI-H1373 cells were sorted by FACS to enrich for the top 50% of eGFP positive cells, and sorted cells were cultured briefly and used to construct scRNA-seq libraries and profiled by 10x scRNA-seq.\nTo carry out the full TraCe-seq experiment, ~600 PC9 cells carrying unique TraCe-seq barcodes were expanded over 12 doublings to establish the barcoded population. A subset of the barcoded PC9 population was used to generate scRNA-seq libraries and profiled by 10x scRNA-seq prior to treatment to establish a baseline transcription profile for each barcoded clone. The rest of the cells were then treated for four days with 1 µM erlotinib, 1 µM GNE-069, or 1 µM GNE-104 respectively. scRNA-seq libraries were then generated form the treated cells and profiled by 10x scRNA-seq.","abstract":"Genetic and non-genetic heterogeneity within cancer cell populations represents a major challenge to anti-cancer therapies. We currently lack robust methods to determine how pre-existing and adaptive features affect cellular responses to therapies. Here, by conducting clonal fitness mapping and transcriptional characterization using expressed barcodes and single-cell RNA-sequencing, we have developed TraCe-seq, a method that captures at clonal resolution the origin, fate, and differential early adaptive transcriptional programs of cells in a complex population in response to distinct treatments. We used TraCe-seq to benchmark how next-generation dual EGFR inhibitors-degraders compare to standard EGFR kinase inhibitors in EGFR-mutant lung cancer cells.\nTo QC the TraCe-seq strategy, single-cell RNA-seq libraries were generated from a variety of human cancer cell lines transduced with the TraCe-seq library to validate the TraCe-seq strategy. Specifically, 5 different cell lines (PC9, MCF-10A, MDA-MB-231, NCI-H358, and NCI-H1373) were each transduced with a unique TraCe-seq barcode. The transduced cells were selected with puromycin only, dissociated to single cell suspensions, and then mixed together. The complex mixture of the 5 cell lines was profiled by 10X scRNA-seq. Furthermore, transduced NCI-H1373 cells were sorted by FACS to enrich for the top 50% of eGFP positive cells, and sorted cells were cultured briefly and used to construct scRNA-seq libraries and profiled by 10x scRNA-seq.\nTo carry out the full TraCe-seq experiment, ~600 PC9 cells carrying unique TraCe-seq barcodes were expanded over 12 doublings to establish the barcoded population. A subset of the barcoded PC9 population was used to generate scRNA-seq libraries and profiled by 10x scRNA-seq prior to treatment to establish a baseline transcription profile for each barcoded clone. The rest of the cells were then treated for four days with 1 µM erlotinib, 1 µM GNE-069, or 1 µM GNE-104 respectively. scRNA-seq libraries were then generated form the treated cells and profiled by 10x scRNA-seq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-21T19:12:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005406","title":"LGSOC 004","description":null,"abstract":"Primary and metastatic tissue samples and germline blood\nsamples were collected from a patient with stage IV LGSOC at the time of primary\ncytoreductive surgery. One year later, at first recurrence, additional tissue samples and\nperipheral blood were also collected. Single gene testing for clinically actionable\nmutations (BRAF V600, KRAS and NRAS) and subsequent whole exome sequencing\n(WES) were performed on 2 primary, 3 metastatic and 2 recurrent tissue samples.\nAdditionally, a ddPCR assay was designed to evaluate the presence of a specific\nmutation in tissue and plasma cfDNA.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005407","title":"Philippine Ayta possess the highest level of Denisovan ancestry in the world","description":"Multiple lines of evidence show that modern humans interbred with archaic Denisovans. Here, we report an account of shared demographic history between Australasians and Denisovans distinctively in Island Southeast Asia. Our analyses are based on ~2.3 million genotypes from 118 ethnic groups of the Philippines including 25 diverse self-identified Negrito populations, along with high-coverage genomes of AustraloPapuans and Ayta Magbukon Negritos. We show that Ayta Magbukon possess the highest level of Denisovan ancestry in the world – ~30-40% greater than that of Australians and Papuans – consistent with an independent admixture event into Negritos from Denisovans. Together with the recently described Homo luzonensis, we suggest that there were multiple archaic species that inhabited the Philippines prior to the arrival of modern humans, and that these archaic groups may have been genetically related. Altogether, our findings unveil a complex intertwined history of modern and archaic humans in the Asia-Pacific region, where distinct Islander Denisovan populations differentially admixed with incoming Australasians across multiple locations and at various points in time.","abstract":"Multiple lines of evidence show that modern humans interbred with archaic Denisovans. Here, we report an account of shared demographic history between Australasians and Denisovans distinctively in Island Southeast Asia. Our analyses are based on ~2.3 million genotypes from 118 ethnic groups of the Philippines including 25 diverse self-identified Negrito populations, along with high-coverage genomes of AustraloPapuans and Ayta Magbukon Negritos. We show that Ayta Magbukon possess the highest level of Denisovan ancestry in the world – ~30-40% greater than that of Australians and Papuans – consistent with an independent admixture event into Negritos from Denisovans. Together with the recently described Homo luzonensis, we suggest that there were multiple archaic species that inhabited the Philippines prior to the arrival of modern humans, and that these archaic groups may have been genetically related. Altogether, our findings unveil a complex intertwined history of modern and archaic humans in the Asia-Pacific region, where distinct Islander Denisovan populations differentially admixed with incoming Australasians across multiple locations and at various points in time.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-22T07:56:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005408","title":"Philippine Ayta possess the highest level of Denisovan ancestry in the world","description":"Multiple lines of evidence show that modern humans interbred with archaic Denisovans. Here, we report an account of shared demographic history between Australasians and Denisovans distinctively in Island Southeast Asia. Our analyses are based on ~2.3 million genotypes from 118 ethnic groups of the Philippines including 25 diverse self-identified Negrito populations, along with high-coverage genomes of AustraloPapuans and Ayta Magbukon Negritos. We show that Ayta Magbukon possess the highest level of Denisovan ancestry in the world – ~30-40% greater than that of Australians and Papuans – consistent with an independent admixture event into Negritos from Denisovans. Together with the recently described Homo luzonensis, we suggest that there were multiple archaic species that inhabited the Philippines prior to the arrival of modern humans, and that these archaic groups may have been genetically related. Altogether, our findings unveil a complex intertwined history of modern and archaic humans in the Asia-Pacific region, where distinct Islander Denisovan populations differentially admixed with incoming Australasians across multiple locations and at various points in time.","abstract":"Multiple lines of evidence show that modern humans interbred with archaic Denisovans. Here, we report an account of shared demographic history between Australasians and Denisovans distinctively in Island Southeast Asia. Our analyses are based on ~2.3 million genotypes from 118 ethnic groups of the Philippines including 25 diverse self-identified Negrito populations, along with high-coverage genomes of AustraloPapuans and Ayta Magbukon Negritos. We show that Ayta Magbukon possess the highest level of Denisovan ancestry in the world – ~30-40% greater than that of Australians and Papuans – consistent with an independent admixture event into Negritos from Denisovans. Together with the recently described Homo luzonensis, we suggest that there were multiple archaic species that inhabited the Philippines prior to the arrival of modern humans, and that these archaic groups may have been genetically related. Altogether, our findings unveil a complex intertwined history of modern and archaic humans in the Asia-Pacific region, where distinct Islander Denisovan populations differentially admixed with incoming Australasians across multiple locations and at various points in time.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-22T08:01:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005409","title":"Denisovan ancestry in Philippine Negritos","description":"Multiple lines of evidence show that modern humans interbred with archaic Denisovans. Here, we report an account of shared demographic history between Australasians and Denisovans distinctively in Island Southeast Asia. Our analyses are based on ~2.3 million genotypes from 118 ethnic groups of the Philippines including 25 diverse self-identified Negrito populations, along with high-coverage genomes of AustraloPapuans and Ayta Magbukon Negritos. We show that Ayta Magbukon possess the highest level of Denisovan ancestry in the world – ~30-40% greater than that of Australians and Papuans – consistent with an independent admixture event into Negritos from Denisovans. Together with the recently described Homo luzonensis, we suggest that there were multiple archaic species that inhabited the Philippines prior to the arrival of modern humans, and that these archaic groups may have been genetically related. Altogether, our findings unveil a complex intertwined history of modern and archaic humans in the Asia-Pacific region, where distinct Islander Denisovan populations differentially admixed with incoming Australasians across multiple locations and at various points in time.","abstract":"Multiple lines of evidence show that modern humans interbred with archaic Denisovans. Here, we report an account of shared demographic history between Australasians and Denisovans distinctively in Island Southeast Asia. Our analyses are based on ~2.3 million genotypes from 118 ethnic groups of the Philippines including 25 diverse self-identified Negrito populations, along with high-coverage genomes of AustraloPapuans and Ayta Magbukon Negritos. We show that Ayta Magbukon possess the highest level of Denisovan ancestry in the world – ~30-40% greater than that of Australians and Papuans – consistent with an independent admixture event into Negritos from Denisovans. Together with the recently described Homo luzonensis, we suggest that there were multiple archaic species that inhabited the Philippines prior to the arrival of modern humans, and that these archaic groups may have been genetically related. Altogether, our findings unveil a complex intertwined history of modern and archaic humans in the Asia-Pacific region, where distinct Islander Denisovan populations differentially admixed with incoming Australasians across multiple locations and at various points in time.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005410","title":"Single cell multi-omics analysis of chromothriptic medulloblastoma highlights genomic and transcriptomic consequences of genome instability","description":"Chromothripsis is a form of genome instability, whereby a presumably single catastrophic event generates extensive genomic rearrangements of one or few chromosome(s). However, little is known about the heterogeneity of chromothripsis across different clones from the same tumor, as well as changes in response to treatment. We analyzed single-cell genomic and transcriptomic alterations linked with chromothripsis in human p53-deficient medulloblastoma (n=7). We reconstructed the order of somatic events, identified early alterations likely linked to chromothripsis and depicted the contribution of chromothripsis to malignancy. We characterized subclonal variation of chromothripsis and its effects on double-minute chromosomes, cancer drivers and putatively druggable targets. Furthermore, we highlighted the causative role and the fitness consequences of specific rearrangements in neural progenitors.","abstract":"Chromothripsis is a form of genome instability, whereby a presumably single catastrophic event generates extensive genomic rearrangements of one or few chromosome(s). However, little is known about the heterogeneity of chromothripsis across different clones from the same tumor, as well as changes in response to treatment. We analyzed single-cell genomic and transcriptomic alterations linked with chromothripsis in human p53-deficient medulloblastoma (n=7). We reconstructed the order of somatic events, identified early alterations likely linked to chromothripsis and depicted the contribution of chromothripsis to malignancy. We characterized subclonal variation of chromothripsis and its effects on double-minute chromosomes, cancer drivers and putatively druggable targets. Furthermore, we highlighted the causative role and the fitness consequences of specific rearrangements in neural progenitors.","study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-04T12:49:46.504316+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005411","title":"Genotyping by OncoArray and Global Screening Array for colorectal cancer risk prediction","description":"The study was conducted to build a Polygenic risk scores (PRS) based on a reported set of 140 single nucleotide polymorphisms that were identified to be associated with a higher risk of colorectal cancer (CRC). Genotyping by OncoArray and Global Screening Array was performed using DNA extracted from blood samples collected at baseline of 187 participants who develop CRC and 176 randomly selected controls without diagnosis of CRC identified within 14 years of follow-up.","abstract":"The study was conducted to build a Polygenic risk scores (PRS) based on a reported set of 140 single nucleotide polymorphisms that were identified to be associated with a higher risk of colorectal cancer (CRC). Genotyping by OncoArray and Global Screening Array was performed using DNA extracted from blood samples collected at baseline of 187 participants who develop CRC and 176 randomly selected controls without diagnosis of CRC identified within 14 years of follow-up.","study_type":"Other","pubmed_ids":[34376648],"external_links":null,"is_released":true,"released_date":"2021-06-22T13:29:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005412","title":"NSCCG CRC GWAS data","description":"Genotype data from 7,281 individuals with colorectal cancer. Genotyped on the Illumina OncoArray. Data has not been quality controlled. Data provided in plink format","abstract":"Genotype data from 7,281 individuals with colorectal cancer. Genotyped on the Illumina OncoArray. Data has not been quality controlled. Data provided in plink format","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-22T16:28:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005413","title":"The Preoperative Presence of Prevotella predicts Anastomotic Healing after Colorectal Surgery","description":null,"abstract":"Anastomotic leakage (AL) is a frequent and potentially life-threatening postoperative complication in pa-tients undergoing colorectal surgery with a multifactorial yet unknown pathophysiology. In the present study, we wish to unravel AL etiology and proper intestinal anastomotic healing (AH) physiology focusing on both gut microbial and host epithelial components. We make use of patients-related samples and two high throughput next generation sequencing approaches, including anastomotic tissue-associated bulk RNA sequencing and preoperative fecal 16S rRNA gene sequencing. We find that in the absence of host epithelial gene expression differences, the preoperative fecal microbiota of patients who undergo colo-rectal resection with successful AH differs in the group of patients who develop AL in the presence of Prevotella at both taxa and enterotype level, and confirm its relevance in postoperative AL-associated complications using feature importance analysis. We suggest a potential beneficial role of Prevotella that may prove useful as predictive biomarkers for proper AH.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005414","title":"Adult-type Granulosa Cell Tumour of the Ovary","description":"A recurrent mutation in FOXL2 (c.402C&gt;G; p.C134W) is present in over 95% of adult-type granulosa cell tumours (AGCTs). In contrast, various loss-of-function mutations in FOXL2 lead to the development of blepharophimosis, ptosis and epicanthus inversus syndrome (BPES). BPES is characterized by an eyelid malformation often accompanied with primary ovarian insufficiency but not granulosa cell tumours. Two recent studies suggest that FOXL2 C402G is a gain or change-of-function mutation with altered DNA-binding specificity. Another study proposes that FOXL2 C402G is selectively targeted for degradation inducing somatic haploinsufficiency suggesting its role as a tumour suppressor. The latter study relies on data indicative of an FOXL2 allelic imbalance in AGCTs. Here we present RNA-seq data as genetic evidence that no real allelic imbalance is observed at the transcriptomic level in AGCTs. Additionally, there is no loss of protein expression in tumours harboring the mutated allele. These data and other features of this mutation as compared to other oncogenes and tumour suppressor genes argue strongly against FOXL2 being a tumour suppressor in this context. Given the likelihood that FOXL2 C402G is oncogenic, targeting the variant protein or its downstream consequences is the most viable path forward to identifying an effective treatment for this cancer.","abstract":"A recurrent mutation in FOXL2 (c.402C&gt;G; p.C134W) is present in over 95% of adult-type granulosa cell tumours (AGCTs). In contrast, various loss-of-function mutations in FOXL2 lead to the development of blepharophimosis, ptosis and epicanthus inversus syndrome (BPES). BPES is characterized by an eyelid malformation often accompanied with primary ovarian insufficiency but not granulosa cell tumours. Two recent studies suggest that FOXL2 C402G is a gain or change-of-function mutation with altered DNA-binding specificity. Another study proposes that FOXL2 C402G is selectively targeted for degradation inducing somatic haploinsufficiency suggesting its role as a tumour suppressor. The latter study relies on data indicative of an FOXL2 allelic imbalance in AGCTs. Here we present RNA-seq data as genetic evidence that no real allelic imbalance is observed at the transcriptomic level in AGCTs. Additionally, there is no loss of protein expression in tumours harboring the mutated allele. These data and other features of this mutation as compared to other oncogenes and tumour suppressor genes argue strongly against FOXL2 being a tumour suppressor in this context. Given the likelihood that FOXL2 C402G is oncogenic, targeting the variant protein or its downstream consequences is the most viable path forward to identifying an effective treatment for this cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-22T21:02:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005415","title":"Immune classification of HCC","description":null,"abstract":"Through integrative genomic analysis, we have refined the immune-related molecular classes of hepatocellular carcinoma and identified a novel inflamed subgroup of tumors that could be associated with response to immune checkpoint inhibitors. We have also defined two non-inflamed classes and propose distinct mechanisms of immune evasion.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005416","title":"FOXL2 in Adult-type Granulosa Cell Tumour of the Ovary - Oncogene or Tumour Suppressor Gene","description":"A recurrent mutation in FOXL2 (c.402C&amp;gt;G; p.C134W) is present in over 95% of adult-type granulosa cell tumours (AGCTs). In contrast, various loss-of-function mutations in FOXL2 lead to the development of blepharophimosis, ptosis and epicanthus inversus syndrome (BPES). BPES is characterized by an eyelid malformation often accompanied with primary ovarian insufficiency but not granulosa cell tumours. Two recent studies suggest that FOXL2 C402G is a gain or change-of-function mutation with altered DNA-binding specificity. Another study proposes that FOXL2 C402G is selectively targeted for degradation inducing somatic haploinsufficiency suggesting its role as a tumour suppressor. The latter study relies on data indicative of an FOXL2 allelic imbalance in AGCTs. Here we present RNA-seq data as genetic evidence that no real allelic imbalance is observed at the transcriptomic level in AGCTs. Additionally, there is no loss of protein expression in tumours harboring the mutated allele. These data and other features of this mutation as compared to other oncogenes and tumour suppressor genes argue strongly against FOXL2 being a tumour suppressor in this context. Given the likelihood that FOXL2 C402G is oncogenic, targeting the variant protein or its downstream consequences is the most viable path forward to identifying an effective treatment for this cancer.","abstract":"A recurrent mutation in FOXL2 (c.402C&amp;gt;G; p.C134W) is present in over 95% of adult-type granulosa cell tumours (AGCTs). In contrast, various loss-of-function mutations in FOXL2 lead to the development of blepharophimosis, ptosis and epicanthus inversus syndrome (BPES). BPES is characterized by an eyelid malformation often accompanied with primary ovarian insufficiency but not granulosa cell tumours. Two recent studies suggest that FOXL2 C402G is a gain or change-of-function mutation with altered DNA-binding specificity. Another study proposes that FOXL2 C402G is selectively targeted for degradation inducing somatic haploinsufficiency suggesting its role as a tumour suppressor. The latter study relies on data indicative of an FOXL2 allelic imbalance in AGCTs. Here we present RNA-seq data as genetic evidence that no real allelic imbalance is observed at the transcriptomic level in AGCTs. Additionally, there is no loss of protein expression in tumours harboring the mutated allele. These data and other features of this mutation as compared to other oncogenes and tumour suppressor genes argue strongly against FOXL2 being a tumour suppressor in this context. Given the likelihood that FOXL2 C402G is oncogenic, targeting the variant protein or its downstream consequences is the most viable path forward to identifying an effective treatment for this cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005417","title":"Genetics causes of male infertility in 185 patient-parent trios from Netherlands and UK","description":"In this, whole exome sequencing was performed on 185 patients suffering from Azoospermia or severe oligozoospermia and on their respective fertile parents in order to investigate de novo and inherited genetic variants likely to be the cause of infertility in these men.\nAfter bioinformatic analysis and comprehensive variant interpretation several de novo point mutations and copy number variations were identified as well as multiple homozygous and compound heterozygous mutations in recessive genes that are likely influencing the infertility phenotypes observed in the patients.","abstract":"In this, whole exome sequencing was performed on 185 patients suffering from Azoospermia or severe oligozoospermia and on their respective fertile parents in order to investigate de novo and inherited genetic variants likely to be the cause of infertility in these men.\nAfter bioinformatic analysis and comprehensive variant interpretation several de novo point mutations and copy number variations were identified as well as multiple homozygous and compound heterozygous mutations in recessive genes that are likely influencing the infertility phenotypes observed in the patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-24T15:01:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005418","title":"Custom long non-coding RNA capture enhances detection sensitivity in different human sample types.","description":"Long non-coding RNAs (lncRNAs) are a heterogeneous group of transcripts that lack protein coding potential and display regulatory functions in various cellular processes. As a result of their cell- and cancer-specific expression patterns, lncRNAs have emerged as potential diagnostic and therapeutic targets. The accurate characterization of lncRNAs in bulk transcriptome data remains challenging due to their low abundance compared to protein coding genes. To tackle this issue, we describe a unique short-read custom lncRNA capture sequencing approach that relies on a comprehensive set of 565,878 capture probes for 49,372 human lncRNA genes. This custom lncRNA capture approach was evaluated on various sample types ranging from artificial high-quality RNA mixtures to more challenging formalin-fixed paraffin-embedded tissue and biofluid material. The custom enrichment approach allows the detection of a more diverse repertoire of lncRNAs, with better reproducibility and higher coverage compared to classic total RNA-sequencing.","abstract":"Long non-coding RNAs (lncRNAs) are a heterogeneous group of transcripts that lack protein coding potential and display regulatory functions in various cellular processes. As a result of their cell- and cancer-specific expression patterns, lncRNAs have emerged as potential diagnostic and therapeutic targets. The accurate characterization of lncRNAs in bulk transcriptome data remains challenging due to their low abundance compared to protein coding genes. To tackle this issue, we describe a unique short-read custom lncRNA capture sequencing approach that relies on a comprehensive set of 565,878 capture probes for 49,372 human lncRNA genes. This custom lncRNA capture approach was evaluated on various sample types ranging from artificial high-quality RNA mixtures to more challenging formalin-fixed paraffin-embedded tissue and biofluid material. The custom enrichment approach allows the detection of a more diverse repertoire of lncRNAs, with better reproducibility and higher coverage compared to classic total RNA-sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-28T09:35:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005419","title":"Molecular profile of IMFT for the identification of potential druggable targets and biomarkers predicting crizotinib response.","description":"The clinical phase II trial EORTC 90101 “CREATE” showed high anti-tumor activity of crizotinib, an ALK/ROS1 inhibitor, in IMFT patients. However, results suggested that other molecular targets in addition to ALK/ROS1 might also contribute to the sensitivity of this kinase inhibitor. We therefore characterized molecular profile of IMFT to identify alterations which could play a role in the response to crizotinib.","abstract":"The clinical phase II trial EORTC 90101 “CREATE” showed high anti-tumor activity of crizotinib, an ALK/ROS1 inhibitor, in IMFT patients. However, results suggested that other molecular targets in addition to ALK/ROS1 might also contribute to the sensitivity of this kinase inhibitor. We therefore characterized molecular profile of IMFT to identify alterations which could play a role in the response to crizotinib.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-28T10:12:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005420","title":"Mutational landscape of high-grade B-cell lymphoma with MYC-, BCL2 and/or BCL6 rearrangements characterized by whole-exome sequencing","description":"To inform on oncogenic drivers, mutational signatures and perturbed pathways in HGBL-DH/TH in comparison with diffuse large-B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), we performed whole-exome sequencing and confirmatory deep panel NGS of 47 clinically annotated cases. Coupled germline DNA was analyzed when available.","abstract":"To inform on oncogenic drivers, mutational signatures and perturbed pathways in HGBL-DH/TH in comparison with diffuse large-B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), we performed whole-exome sequencing and confirmatory deep panel NGS of 47 clinically annotated cases. Coupled germline DNA was analyzed when available.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-28T14:20:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005421","title":"COIN CRC GWAS data","description":"Genotype data from the COIN and COIN-B trials of advanced/metastatic colorectal cancer. Data provided in plink format, and has been quality controlled. Control data used was from the WTCCC2 project National Blood Donors (NBS) Cohort (EGAD00000000024).","abstract":"Genotype data from the COIN and COIN-B trials of advanced/metastatic colorectal cancer. Data provided in plink format, and has been quality controlled. Control data used was from the WTCCC2 project National Blood Donors (NBS) Cohort (EGAD00000000024).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-28T16:30:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005422","title":"Integration of genomics and metabolomics in acute myeloid leukemia","description":"Although targeting of cell metabolism is a promising therapeutic strategy in acute myeloid leukemia (AML), metabolic dependencies are largely unexplored. We aimed to classify AML patients based on their metabolic landscape and map connections between metabolic and genomic profiles. The intracellular metabolome distinguished three AML clusters, correlating with distinct genomic profiles: NPM1-mutated(mut), chromatin/spliceosome-mut and TP53-mut/aneuploid AML that were confirmed by biofluid analysis.","abstract":"Although targeting of cell metabolism is a promising therapeutic strategy in acute myeloid leukemia (AML), metabolic dependencies are largely unexplored. We aimed to classify AML patients based on their metabolic landscape and map connections between metabolic and genomic profiles. The intracellular metabolome distinguished three AML clusters, correlating with distinct genomic profiles: NPM1-mutated(mut), chromatin/spliceosome-mut and TP53-mut/aneuploid AML that were confirmed by biofluid analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-28T17:47:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005423","title":"ANGIOPREDICT - an FP7-funded project enabling personalised medicine for patients with metastatic colorectal cancer.","description":"In ANGIOPREDICT, academic cancer biologists and industry-based biotechnology researchers will work together with clinicians to identify biomarkers to predict whether individual metastatic colorectal cancer patients will respond positively to Avastin® combination therapy. Diagnostic tests using these biomarkers will also be developed to provide clinicians with the means to predict patient treatment responses in the future.","abstract":"In ANGIOPREDICT, academic cancer biologists and industry-based biotechnology researchers will work together with clinicians to identify biomarkers to predict whether individual metastatic colorectal cancer patients will respond positively to Avastin® combination therapy. Diagnostic tests using these biomarkers will also be developed to provide clinicians with the means to predict patient treatment responses in the future.","study_type":"Other","pubmed_ids":[28611295,30291241,32555399],"external_links":null,"is_released":true,"released_date":"2021-06-29T10:02:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005424","title":"Chromothripsis followed by circular recombination drives oncogene amplification in human cancer","description":"The mechanisms behind the evolution of complex genomic amplifications in cancer have remained largely unclear. We here identified a type of amplification, termed as “seismic amplification”, that is characterized by multiple rearrangements and discontinuous copy number levels. Seismic amplifications occurred in 9.9% (274/2,756) of cases across 38 cancer types and were associated with massively increased copy numbers and elevated oncogene expression. Reconstruction of the development of seismic amplification revealed a stepwise evolution, starting with a chromothripsis event, followed by formation of circular extrachromosomal DNA that subsequently underwent repetitive rounds of circular recombination. The resulting amplicons persisted as extrachromosomal DNA circles or had reintegrated into the genome in overt tumors. Together, our data indicate that the sequential occurrence of chromothripsis and circular recombination drives oncogene amplification and over-expression in a substantial fraction of human malignancies.","abstract":"The mechanisms behind the evolution of complex genomic amplifications in cancer have remained largely unclear. We here identified a type of amplification, termed as “seismic amplification”, that is characterized by multiple rearrangements and discontinuous copy number levels. Seismic amplifications occurred in 9.9% (274/2,756) of cases across 38 cancer types and were associated with massively increased copy numbers and elevated oncogene expression. Reconstruction of the development of seismic amplification revealed a stepwise evolution, starting with a chromothripsis event, followed by formation of circular extrachromosomal DNA that subsequently underwent repetitive rounds of circular recombination. The resulting amplicons persisted as extrachromosomal DNA circles or had reintegrated into the genome in overt tumors. Together, our data indicate that the sequential occurrence of chromothripsis and circular recombination drives oncogene amplification and over-expression in a substantial fraction of human malignancies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-29T14:46:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005425","title":"Test study","description":null,"abstract":"dsadasd","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005426","title":"Sequence Data from the phase 2 PrE0505 trial of Durvalumab with First Line Platinum-Pemetrexed for Unresectable Pleural Mesothelioma","description":"Mesothelioma is a rare and fatal cancer with limited therapeutic options until the recent approval of combination immune checkpoint blockade. We report the results of the phase 2 PrE0505 trial (NCT02899195) of the anti-PD-L1 antibody, durvalumab, plus platinum-based and pemetrexed chemotherapy for patients with previously untreated unresectable pleural mesothelioma. The primary endpoint was overall survival compared to historic control with cisplatin and pemetrexed chemotherapy. The combination of durvalumab with chemotherapy met the pre-specified primary endpoint reaching a median survival of 20.4 months vs. 12.1 months with historic control. Treatment emergent adverse events were consistent with known side effects of chemotherapy and all adverse events due to immunotherapy were grade ≤2. Integrated genomic and immune cell repertoire analyses revealed that a higher immunogenic mutation burden coupled with a more diverse T cell repertoire were linked with favorable clinical outcome. Structural genome-wide analyses demonstrated a higher degree of genomic instability in responding tumors of epithelioid histology. Patients with germline alterations in cancer predisposing genes, especially those involved in DNA repair, were more likely to attain long term survival. Our findings indicate that concurrent durvalumab with platinum-based chemotherapy has promising clinical activity and that responses are driven by the complex genomic background of malignant pleural mesothelioma.","abstract":"Mesothelioma is a rare and fatal cancer with limited therapeutic options until the recent approval of combination immune checkpoint blockade. We report the results of the phase 2 PrE0505 trial (NCT02899195) of the anti-PD-L1 antibody, durvalumab, plus platinum-based and pemetrexed chemotherapy for patients with previously untreated unresectable pleural mesothelioma. The primary endpoint was overall survival compared to historic control with cisplatin and pemetrexed chemotherapy. The combination of durvalumab with chemotherapy met the pre-specified primary endpoint reaching a median survival of 20.4 months vs. 12.1 months with historic control. Treatment emergent adverse events were consistent with known side effects of chemotherapy and all adverse events due to immunotherapy were grade ≤2. Integrated genomic and immune cell repertoire analyses revealed that a higher immunogenic mutation burden coupled with a more diverse T cell repertoire were linked with favorable clinical outcome. Structural genome-wide analyses demonstrated a higher degree of genomic instability in responding tumors of epithelioid histology. Patients with germline alterations in cancer predisposing genes, especially those involved in DNA repair, were more likely to attain long term survival. Our findings indicate that concurrent durvalumab with platinum-based chemotherapy has promising clinical activity and that responses are driven by the complex genomic background of malignant pleural mesothelioma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-06-30T02:11:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005427","title":"Study to test validation","description":null,"abstract":"Study to test validation","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005428","title":"Normal_and_cancer_predisposed_kidney","description":"LCM of normal, predisposed, and cancerous kidney tissue for NanoSeq analysis.","abstract":"We intend to use laser capture microdissection to study normal kidneys and kidneys of various pathologies, including clear cell carcinoma, germline predisposition syndromes like von Hippel-Lindau (VHL), Succinate Dehydrogenase (SDH), and Birt-Hogg-Dubé syndromes, and diseases of nephron, duct, or glomeruli.  Previous LCM study of this tissue has proven challenging to analyze due to the prohibitively small size of clonal units.  With the development of NanoSeq by Inigo Martincorena and Fede Abascal, discernable signal can be ascertained from smaller amounts of DNA, allowing us to learn from the smallest normal, precancerous, and cancerous structures.  Using these techniques, we hope to [1] understand more about the landscape of somatic mutation and evolution in the normal and predisposed kidney, [2] identify genomic changes in the earliest lesions with VHL mutations, [3] explore genomic signatures of kidney diseases of unknown etiology, and [4] collect data to add to a cross-tissue model of the dynamics of clonal expansion and carcinogenesis.\n\n\tIn addition to characterizing the clonal landscape of normal kidney, we are particularly interested in exploring the earliest changes to the kidney due to mutations in the VHL tumor suppressor gene, which regulates hypoxia-inducible factor-1 and is associated with both hereditary and sporadic renal clear cell carcinomas.  To identify these changes in morphologically normal cells, we plan to stain slides with CAIX antibody, first used for this purpose by Mandriota, et al. Cancer Cell (2002).  CAIX, the protein product of the CA9 gene regulated by VHL and HIF, serves as a label for HIF activation in the absence of fully functional VHL.  The structures illuminated by CAIX antibody on one section will serve as a guide for LCM cuts of VHL deficient cells on the adjacent section.  By sequencing these very early lesions in proximal and distal ducts of the kidney, we can begin to understand more of the clonal development of cells with “one hit” of the two-hit carcinogenesis model.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005429","title":"WES on tumor DNA and germline DNA in pediatric cancer","description":"This dataset contains whole exome sequencing (WES) data from tumor DNA samples of various pediatric cancer entities. Files are provided in fastq format. Samples were sequenced on a Novaseq6000 or Hiseq2500 (Illumina). Data analysis is available at https://github.com/rmvpaeme/sWGS_pediatric_cancer.","abstract":"This dataset contains whole exome sequencing (WES) data from tumor DNA samples of various pediatric cancer entities. Files are provided in fastq format. Samples were sequenced on a Novaseq6000 or Hiseq2500 (Illumina). Data analysis is available at https://github.com/rmvpaeme/sWGS_pediatric_cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-01T10:24:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005430","title":"Feasibility of Ultra-Rapid Exome Sequencing in Critically Ill Infants and Children With Suspected Monogenic Conditions in the Australian Public Health Care System","description":"Critically ill infants and children with suspected monogenic conditions underwent ultra-rapid whole exome genetic testing. A molecular diagnosis was established in 51% of the patients. This study suggests feasibility of ultra-rapid genomic testing in critically ill pediatric patients.","abstract":"Critically ill infants and children with suspected monogenic conditions underwent ultra-rapid whole exome genetic testing. A molecular diagnosis was established in 51% of the patients. This study suggests feasibility of ultra-rapid genomic testing in critically ill pediatric patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-01T10:39:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005431","title":"Targeted deep sequencing on Pediatric MDS","description":"Targeted NGS using custom panels with SAMD9, SAMD9L genes and 22 single nucleotide polymorphisms (SNP) on chromosome 7q (allele frequency &gt;35% in all ethnic sub-populations in gnomAD) (Ampliseq #IAD10417) was performed in 667/669 cases. Additionally, 559 cases were sequenced using 28 pediatric MDS genes (GATA2, RUNX1, HOXA9, CEBPA, GATA1, KRAS, NRAS, CBL, PTPN11, ASXL1, EZH2, SETBP1, FLT3, KIT, JAK2, JAK3, CSF3R, MPL, SH2, BCOR, BCORL1; RAD21, STAG2, CTCF, TP53, PTEN, CALR, VPS45; Ampliseq #IAD51150). Libraries for targeted NGS were prepared using NEBNext Ultra II DNA library prep kit (New England BioLabs, cat#E7645S/L) per manufacturer’s instruction and samples were sequenced on an Illumina Miseq 2000 with 2 x 150 bp reads. The BAM files are uploaded here.","abstract":"Targeted NGS using custom panels with SAMD9, SAMD9L genes and 22 single nucleotide polymorphisms (SNP) on chromosome 7q (allele frequency &gt;35% in all ethnic sub-populations in gnomAD) (Ampliseq #IAD10417) was performed in 667/669 cases. Additionally, 559 cases were sequenced using 28 pediatric MDS genes (GATA2, RUNX1, HOXA9, CEBPA, GATA1, KRAS, NRAS, CBL, PTPN11, ASXL1, EZH2, SETBP1, FLT3, KIT, JAK2, JAK3, CSF3R, MPL, SH2, BCOR, BCORL1; RAD21, STAG2, CTCF, TP53, PTEN, CALR, VPS45; Ampliseq #IAD51150). Libraries for targeted NGS were prepared using NEBNext Ultra II DNA library prep kit (New England BioLabs, cat#E7645S/L) per manufacturer’s instruction and samples were sequenced on an Illumina Miseq 2000 with 2 x 150 bp reads. The BAM files are uploaded here.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-01T15:57:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005432","title":"Whole exome sequencing on Pediatric MDS patients","description":"WES was performed on 126 cases (SAMD9/9Lmut: 64/67; GATA2mut 24/35, MDS wildtype 38/471) using SureSelect Human All Exon V6 enrichment (Agilent, cat# 5190-8863). The generated libraries were sequenced on the Illumina Hiseq 2500 with 150bp paired-end reads. FASTQ files were processed using SeqNext platform (JSI medical system, Germany), with gene-based alignment to a virtual panel of 300 genes consisting of genes relevant to bone marrow failure, MDS predisposition, and hematological cancers as per the Pan-Cancer studies with cohorts of &gt;10,000 cancers. The generated BAM files are submitted here.","abstract":"WES was performed on 126 cases (SAMD9/9Lmut: 64/67; GATA2mut 24/35, MDS wildtype 38/471) using SureSelect Human All Exon V6 enrichment (Agilent, cat# 5190-8863). The generated libraries were sequenced on the Illumina Hiseq 2500 with 150bp paired-end reads. FASTQ files were processed using SeqNext platform (JSI medical system, Germany), with gene-based alignment to a virtual panel of 300 genes consisting of genes relevant to bone marrow failure, MDS predisposition, and hematological cancers as per the Pan-Cancer studies with cohorts of &gt;10,000 cancers. The generated BAM files are submitted here.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-01T15:58:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005433","title":"Single-cell DNA sequencing on Pediatric MDS","description":"Single-cell DNA sequencing with antibody-oligonucleotide staining was performed using the Mission Bio Tapestri single-cell DNA sequencing platform, per the manufacturer’s instructions. All libraries were sized and quantified using an Agilent Bioanalyzer and pooled for sequencing on an Illumina NovaSeq6000 with 150 base-paired ending multiplexed runs.\nFastq files generated by the sequencers were processed using the Tapestri Pipeline V2 and included adapter trimming, sequence alignment (BWA), barcode correction, cell finding, and variant calling (GATK v4/Haplotypecaller). FastQ files are provided for the 5 samples that were processed using the aforementioned pipeline.","abstract":"Single-cell DNA sequencing with antibody-oligonucleotide staining was performed using the Mission Bio Tapestri single-cell DNA sequencing platform, per the manufacturer’s instructions. All libraries were sized and quantified using an Agilent Bioanalyzer and pooled for sequencing on an Illumina NovaSeq6000 with 150 base-paired ending multiplexed runs.\nFastq files generated by the sequencers were processed using the Tapestri Pipeline V2 and included adapter trimming, sequence alignment (BWA), barcode correction, cell finding, and variant calling (GATK v4/Haplotypecaller). FastQ files are provided for the 5 samples that were processed using the aforementioned pipeline.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-01T15:58:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005434","title":"Spatial concordance of DNA methylation classification in diffuse glioma","description":"Background: Intratumoral heterogeneity is a hallmark of diffuse gliomas. DNA methylation profiling is an emerging approach in the clinical classification of brain tumors. The goal of this study is to investigate the effects of intratumoral heterogeneity on classification confidence.\n\nMethods: We used neuronavigation to acquire 133 image-guided and spatially-separated stereotactic biopsy samples from 16 adult patients with a diffuse glioma (7 IDH-wildtype and 2 IDH-mutant glioblastoma, 6 diffuse astrocytoma, IDH-mutant and 1 oligodendroglioma, IDH-mutant and 1p19q codeleted), which we characterized using DNA methylation arrays. Samples were obtained from regions with and without abnormalities on contrast enhanced T1 weighted and fluid-attenuated inversion recovery MRI. Methylation profiles were analyzed to devise a three-dimensional reconstruction of (epi)genetic heterogeneity. Tumor purity was assessed from clonal methylation sites.\n\nResults: Molecular aberrations indicated that tumor was found outside imaging abnormalities, underlining the infiltrative nature of this tumor and the limitations of current routine imaging modalities. We demonstrate that tumor purity is highly variable between samples and explains a substantial part of apparent epigenetic spatial heterogeneity. We observed that DNA methylation subtypes are often, but not always, conserved in space taking tumor purity and prediction accuracy into account.\n\nConclusion: Our results underscore the infiltrative nature of diffuse gliomas and suggest that DNA methylation subtypes are relatively concordant in this tumor type, although some heterogeneity exists.","abstract":"Background: Intratumoral heterogeneity is a hallmark of diffuse gliomas. DNA methylation profiling is an emerging approach in the clinical classification of brain tumors. The goal of this study is to investigate the effects of intratumoral heterogeneity on classification confidence.\n\nMethods: We used neuronavigation to acquire 133 image-guided and spatially-separated stereotactic biopsy samples from 16 adult patients with a diffuse glioma (7 IDH-wildtype and 2 IDH-mutant glioblastoma, 6 diffuse astrocytoma, IDH-mutant and 1 oligodendroglioma, IDH-mutant and 1p19q codeleted), which we characterized using DNA methylation arrays. Samples were obtained from regions with and without abnormalities on contrast enhanced T1 weighted and fluid-attenuated inversion recovery MRI. Methylation profiles were analyzed to devise a three-dimensional reconstruction of (epi)genetic heterogeneity. Tumor purity was assessed from clonal methylation sites.\n\nResults: Molecular aberrations indicated that tumor was found outside imaging abnormalities, underlining the infiltrative nature of this tumor and the limitations of current routine imaging modalities. We demonstrate that tumor purity is highly variable between samples and explains a substantial part of apparent epigenetic spatial heterogeneity. We observed that DNA methylation subtypes are often, but not always, conserved in space taking tumor purity and prediction accuracy into account.\n\nConclusion: Our results underscore the infiltrative nature of diffuse gliomas and suggest that DNA methylation subtypes are relatively concordant in this tumor type, although some heterogeneity exists.","study_type":"Other","pubmed_ids":[34049406],"external_links":null,"is_released":true,"released_date":"2021-07-01T18:57:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005435","title":"Risk alleles of membranous nephropathy and recurrence of the disease on the grafted kidney","description":"The goal of the project was to identify risk alleles that are associated with recurrence of membranous nephropathy in the graft after kidney transplantation. First, we sequenced PLA2R1 and HLA-D loci in 248 patients with primary membranous nephropathy and identified two independent single nucleotide polymorphisms (SNPs) at risk for primary membranous nephropathy at each locus. Then we investigated whether primary membranous nephropathy at-risk variants were associated with recurrence in a retrospective cohort of 105 donor-recipient pairs and a replication cohort of 40 pairs.","abstract":"The goal of the project was to identify risk alleles that are associated with recurrence of membranous nephropathy in the graft after kidney transplantation. First, we sequenced PLA2R1 and HLA-D loci in 248 patients with primary membranous nephropathy and identified two independent single nucleotide polymorphisms (SNPs) at risk for primary membranous nephropathy at each locus. Then we investigated whether primary membranous nephropathy at-risk variants were associated with recurrence in a retrospective cohort of 105 donor-recipient pairs and a replication cohort of 40 pairs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-02T07:36:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005436","title":"G-SAM: Transcriptional Evolution of Glioblastomas Treated With Standard of Care","description":"Collection of mostly matching primary and recurrent glioblastoma RNA-seq sample pairs, also matching with an earlier DNA sequencing study","abstract":"Collection of mostly matching primary and recurrent glioblastoma RNA-seq sample pairs, also matching with an earlier DNA sequencing study","study_type":"Other","pubmed_ids":[31743054,34608482,36898379],"external_links":null,"is_released":true,"released_date":"2021-07-02T13:11:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005437","title":"Intellance-2: omics data on recurrent glioblastoma patients participating in the Intellance-2 clinical trial, prior to treatment.","description":"This study contains omics data from patients from the Intellance-2 clinical trial, in which effectiveness of ABT414 in EGFR amplified recurrent glioblastoma patients was tested. Patients were randomly assigned to one of three arms: (1) standard of care treatement (TMZ or CCNU), (2) Only ABT414 and (3) ABT414 + (TMZ|CCNU)","abstract":"This study contains omics data from patients from the Intellance-2 clinical trial, in which effectiveness of ABT414 in EGFR amplified recurrent glioblastoma patients was tested. Patients were randomly assigned to one of three arms: (1) standard of care treatement (TMZ or CCNU), (2) Only ABT414 and (3) ABT414 + (TMZ|CCNU)","study_type":"Other","pubmed_ids":[32642719,34608482],"external_links":null,"is_released":true,"released_date":"2021-07-02T13:31:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005438","title":"MicMac","description":null,"abstract":"MicMac","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005439","title":"Developmental_states_of_localised_and_metastatic_osteosarcoma_cells","description":"Developmental states of localised and metastatic osteosarcoma cells – a knowledge bank for novel biomarkers and therapeutic approaches.","abstract":"The aim of this project is to identify the somatic mutations and hence the critical genes involved in the development of bone cancers through the sequencing of bone cancer genomes and normal DNAs from the same individuals. Tumour DNA will be analysed and compared to the matching constitutional (normal) DNA from the same patient to identify tumour-acquired (somatic) alterations. These alterations will be identified in multiple tumours and then these set compared against each other to determine which genes are mutated in common and which pathways have been targeted.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005440","title":"Developmental_states_of_localised_and_metastatic_osteosarcoma_cells","description":"Developmental states of localised and metastatic osteosarcoma cells – a knowledge bank for novel biomarkers and therapeutic approaches.","abstract":"The aim of this project is to identify the somatic mutations and hence the critical genes involved in the development of bone cancers through the sequencing of bone cancer genomes and normal DNAs from the same individuals. Tumour DNA will be analysed and compared to the matching constitutional (normal) DNA from the same patient to identify tumour-acquired (somatic) alterations. These alterations will be identified in multiple tumours and then these set compared against each other to determine which genes are mutated in common and which pathways have been targeted.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005441","title":"Body map","description":"Somatic mutations accumulated in normal tissues are associated with aging and disease. Here, we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies (~ 600 cells each) of nine organs from five donors. We found that somatic mutation accumulations and clonal expansions are widespread, although to variable extents, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for tissues from esophagus and cardia. Endogenous mutational processes like SBS1 and SBS5 are ubiquitous among normal tissues though exhibiting different relative activities. Exogenous mutational processes operate in multiple tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimeter resolution. In esophagus and cardia, macroscopic somatic clones that expanded to hundreds of micrometers were frequently seen, whereas in tissues like colon, rectum, and duodenum, somatic clones were microscopic in size and evolved independently, possibly restricted by local tissue micro-structures. Our study depicted a body map of somatic mutations and clonal expansions from the same individuals, and it revealed that the degree of somatic clonal expansion and enrichment of driver mutations are highly organ specific.","abstract":"Somatic mutations accumulated in normal tissues are associated with aging and disease. Here, we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies (~ 600 cells each) of nine organs from five donors. We found that somatic mutation accumulations and clonal expansions are widespread, although to variable extents, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for tissues from esophagus and cardia. Endogenous mutational processes like SBS1 and SBS5 are ubiquitous among normal tissues though exhibiting different relative activities. Exogenous mutational processes operate in multiple tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimeter resolution. In esophagus and cardia, macroscopic somatic clones that expanded to hundreds of micrometers were frequently seen, whereas in tissues like colon, rectum, and duodenum, somatic clones were microscopic in size and evolved independently, possibly restricted by local tissue micro-structures. Our study depicted a body map of somatic mutations and clonal expansions from the same individuals, and it revealed that the degree of somatic clonal expansion and enrichment of driver mutations are highly organ specific.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005442","title":"Whole exome sequencing (bam files) of 55 samples of myxofibrosarcoma and 44 matched pairs","description":"Myxofibrosarcoma (MFS) is a rare subtype of sarcomas in the elderly, whose genetic basis is poorly understood. To elucidate it, the whole exome sequence was performed.","abstract":"Myxofibrosarcoma (MFS) is a rare subtype of sarcomas in the elderly, whose genetic basis is poorly understood. To elucidate it, the whole exome sequence was performed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-05T10:53:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005443","title":"Targeted-capture sequencing (bam files) of 81 samples of myxofibrosarcoma and 44 matched pairs","description":"Myxofibrosarcoma (MFS) is a rare subtype of sarcomas in the elderly, whose genetic basis is poorly understood. To elucidate it, the Targeted-capture sequencing was performed.","abstract":"Myxofibrosarcoma (MFS) is a rare subtype of sarcomas in the elderly, whose genetic basis is poorly understood. To elucidate it, the Targeted-capture sequencing was performed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-05T11:05:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005444","title":"Whole genome sequencing (bam files) of 5 samples of myxofibrosarcoma and 5 matched pairs","description":"Myxofibrosarcoma (MFS) is a rare subtype of sarcomas in the elderly, whose genetic basis is poorly understood. To elucidate it, the whole genome sequence was performed.","abstract":"Myxofibrosarcoma (MFS) is a rare subtype of sarcomas in the elderly, whose genetic basis is poorly understood. To elucidate it, the whole genome sequence was performed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-05T11:05:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005445","title":"HCA_Embryo_Foetal_WSSS_Dev_RNA_Sanger","description":"Detailed single cell atlas of whole human embryos","abstract":"We propose to generate an in-depth single cell and spatial atlas of human embryos during late organogenesis, at 6/7 post conception weeks (PCW). We will deploy genomics technologies to profile single cells from dissociated tissues and within intact tissue sections, and deploy cutting-edge computational methods to reconstruct, in silico, a three-dimensional atlas of the whole human embryo. \n\nDetailed single cell atlas of whole human embryos\nDeliverables: Complete whole embryo atlas datasets by high-throughput genomics profiling (single cell RNA-sequencing (scRNA-seq), single nuclear RNA-sequencing (snRNA-seq), and accessible chromatin sequencing (ATAC-seq)); and spatial transcriptomics (ST, e.g. 10x Genomics Visium), in situ sequencing (ISS) and multiplex smFISH analysis of tissue sections.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005446","title":"Induction of trained immunity by influenza vaccine: impact on COVID-19","description":null,"abstract":"Cross-protective effects of certain vaccines against heterologous infections have been reported, and long-term boosting of innate immunity (also termed trained immunity) has been proposed as the underlying mechanism. Several epidemiological studies suggested cross-protection between influenza vaccination and COVID-19 during the current pandemic. Influenza vaccine responses included significant transcriptional reprogramming of monocytes, while systemic inflammation was reduced. These epidemiological and immunological data argue for a potential beneficial effect of influenza vaccination against COVID-19.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-05T12:31:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005447","title":"HCA_Gonads_Foetal_Vento_DNA","description":"Cell atlas of human gonads","abstract":"HDBR 200539 - Human Gonads cell atlas. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess human development. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005448","title":"SMARCA4/2 loss inhibits chemotherapy-induced apoptosis by restricting IP3R3-mediated Ca2+ flux to mitochondria","description":null,"abstract":"Inactivating mutations in SMARCA4 and concurrent epigenetic silencing of SMARCA2 characterize subsets of ovarian and lung cancers. Concomitant loss of these key subunits of SWI/SNF chromatin remodeling complexes in both cancers is associated with chemotherapy resistance and poor prognosis. Here, we discover that SMARCA4/2 loss inhibits chemotherapy-induced apoptosis through disrupting intracellular organelle calcium ion (Ca2+) release in these cancers. By restricting chromatin accessibility to ITPR3, encoding Ca2+ channel IP3R3, SMARCA4/2 deficiency causes reduced IP3R3 expression leading to impaired Ca2+ transfer from the endoplasmic reticulum to mitochondria required for apoptosis induction. Reactivation of SMARCA2 by a histone deacetylase inhibitor rescues IP3R3 expression and enhances cisplatin response in SMARCA4/2-deficient cancer cells both in vitro and in vivo. Our findings elucidate the contribution of SMARCA4/2 to Ca2+-dependent apoptosis induction, which may be exploited to enhance chemotherapy response in SMARCA4/2-deficient cancers.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-06T03:24:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005449","title":"MutWP4__CRUK_Grand_Challenge_Mutographs_of_Cancer__organoid_control_WGS","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, Kings College London will characterise the mutational signatures induced by putative human carcinogens in order to identify the origins of mutational signatures found in human cancers. To achieve this human organoid cell cultures will be exposed to a representative catalogue of known or suspected human carcinogens and mutagens and, using whole genome sequencing, the patterns of mutations induced by them will be determined. Somatic mutational signatures will be subsequently extracted by non-negative matrix factorisation methods and correlated with exposure data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, Kings College London will characterise the mutational signatures induced by putative human carcinogens in order to identify the origins of mutational signatures found in human cancers. To achieve this human organoid cell cultures will be exposed to a representative catalogue of known or suspected human carcinogens and mutagens and, using whole genome sequencing, the patterns of mutations induced by them will be determined. Somatic mutational signatures will be subsequently extracted by non-negative matrix factorisation methods and correlated with exposure data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development. 20X","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-06T11:58:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005450","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__head___neck","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-06T12:47:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005451","title":"MutWP1__CRUK_Grand_Challenge__normal_kidney_Nanoseq","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-06T13:02:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005452","title":"MutWP4__CRUK_Grand_Challenge_Mutographs_of_Cancer__RNAseq","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, Kings College London will characterise the mutational signatures induced by putative human carcinogens in order to identify the origins of mutational signatures found in human cancers. To achieve this human organoid cell cultures will be exposed to a representative catalogue of known or suspected human carcinogens and mutagens and, using whole genome sequencing, the patterns of mutations induced by them will be determined. Somatic mutational signatures will be subsequently extracted by non-negative matrix factorisation methods and correlated with exposure data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, Kings College London will characterise the mutational signatures induced by putative human carcinogens in order to identify the origins of mutational signatures found in human cancers. To achieve this human organoid cell cultures will be exposed to a representative catalogue of known or suspected human carcinogens and mutagens and, using whole genome sequencing, the patterns of mutations induced by them will be determined. Somatic mutational signatures will be subsequently extracted by non-negative matrix factorisation methods and correlated with exposure data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005453","title":"Predictive value of chromosome 18q11.2-q12.1 loss for benefit from bevacizumab in metastatic colorectal cancer; a post-hoc analysis of the randomized controlled trial AGITG-MAX","description":"Patients and methods:  We analyzed tumor samples of 256 patients enrolled in the AGITG-MAX 3-arm randomized controlled trial (RCT) who were randomly assigned to receive either capecitabine,  or capecitabine and bevacizumab with- or without mitomycin. Chromosome 18q11.2-q12.1 copy number status was measured and correlated with PFS according to a predefined analysis plan with marker-treatment interaction as the primary end-point.Results: Chromosome 18q11.2-q12.1 losses were detected in 71% of patients (181/256) characteristic for mCRC. Consistent with the non-randomized study, significant PFS benefit of bevacizumab was observed in chromosome 18q11.2-q12.1 loss patients (P=0.009), and not in 18q no-loss patients (P=0.67). Although significance for marker-treatment interaction was not reached (Pinteraction = 0.28), hazard ratio and 95% confidence interval (HRinteraction 0.72, CI 0.39 - 1.32) show striking overlap with the non-randomized study cohorts (HRinteraction 0.41, CI 0.32 - 0.8) supported by a non-significant Cochrane chi-squared (P=0.11) for heterogeneity. Conclusions: PFS characteristics for marker positive- and negative patients randomized for treatment with- or without bevacizumab were consistent with those of the non-randomized discovery study, though the number of AGITG-MAX samples fell short to reach significance for marker-treatment interaction. Post-hoc analysis of the AGITG-MAX RCT provides supportive evidence for chromosome 18q11.2-q12.1 as a clinically relevant predictive marker for mCRC patients.","abstract":"Patients and methods:  We analyzed tumor samples of 256 patients enrolled in the AGITG-MAX 3-arm randomized controlled trial (RCT) who were randomly assigned to receive either capecitabine,  or capecitabine and bevacizumab with- or without mitomycin. Chromosome 18q11.2-q12.1 copy number status was measured and correlated with PFS according to a predefined analysis plan with marker-treatment interaction as the primary end-point.Results: Chromosome 18q11.2-q12.1 losses were detected in 71% of patients (181/256) characteristic for mCRC. Consistent with the non-randomized study, significant PFS benefit of bevacizumab was observed in chromosome 18q11.2-q12.1 loss patients (P=0.009), and not in 18q no-loss patients (P=0.67). Although significance for marker-treatment interaction was not reached (Pinteraction = 0.28), hazard ratio and 95% confidence interval (HRinteraction 0.72, CI 0.39 - 1.32) show striking overlap with the non-randomized study cohorts (HRinteraction 0.41, CI 0.32 - 0.8) supported by a non-significant Cochrane chi-squared (P=0.11) for heterogeneity. Conclusions: PFS characteristics for marker positive- and negative patients randomized for treatment with- or without bevacizumab were consistent with those of the non-randomized discovery study, though the number of AGITG-MAX samples fell short to reach significance for marker-treatment interaction. Post-hoc analysis of the AGITG-MAX RCT provides supportive evidence for chromosome 18q11.2-q12.1 as a clinically relevant predictive marker for mCRC patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-06T16:12:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005454","title":"IMCISION RNAseq","description":"RNA sequencing could be performed on all 32 baseline and 30 on-treatment primary tumor biopsies. Based on gene-set enrichment analysis, the epithelial to mesenchymal transition signature was enriched in baseline tumors of patients without MPR, though its expression was insufficient to predict ICB response. Baseline and on-treatment IFNγ and T-cell signature expression (Z-score) were not significantly higher in patients with an MPR.­­­\nBaseline primary tumor hypoxia-associated gene expression in IMCISION did not predict ICB response. However, on-treatment biopsies of MPR tumor samples showed significantly lower hypoxia gene expression when compared to non-MPR samples. Moreover, in a paired analysis of baseline and corresponding on-treatment samples, a significant decrease of hypoxia-related gene expression was observed in MPR biopsies, while this decrease was absent in non-MPR biopsies.","abstract":"RNA sequencing could be performed on all 32 baseline and 30 on-treatment primary tumor biopsies. Based on gene-set enrichment analysis, the epithelial to mesenchymal transition signature was enriched in baseline tumors of patients without MPR, though its expression was insufficient to predict ICB response. Baseline and on-treatment IFNγ and T-cell signature expression (Z-score) were not significantly higher in patients with an MPR.­­­\nBaseline primary tumor hypoxia-associated gene expression in IMCISION did not predict ICB response. However, on-treatment biopsies of MPR tumor samples showed significantly lower hypoxia gene expression when compared to non-MPR samples. Moreover, in a paired analysis of baseline and corresponding on-treatment samples, a significant decrease of hypoxia-related gene expression was observed in MPR biopsies, while this decrease was absent in non-MPR biopsies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-07T14:25:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005455","title":"Misoprostol-induced high fever GWAS study","description":"Genome-wide association (GWAS) meta-analysis study of misoprostol-induced fever was conducted on two South American cohorts (Argentina and Ecuador). DNA was collected from blood of women who were screened for postpartum haemorrhage (PPH) and administered misoprostol were included in the study. Genotypes were  acquired from the Global Screening Array (Illumina). Meta-analysis of these cohorts was completed using METAL software.","abstract":"Genome-wide association (GWAS) meta-analysis study of misoprostol-induced fever was conducted on two South American cohorts (Argentina and Ecuador). DNA was collected from blood of women who were screened for postpartum haemorrhage (PPH) and administered misoprostol were included in the study. Genotypes were  acquired from the Global Screening Array (Illumina). Meta-analysis of these cohorts was completed using METAL software.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-07T15:49:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005456","title":"DSScitrobacter","description":"Sequencing study of the effect of intestinal challenge on different murine organs","abstract":"WT mice were given 2% DSS, Citrobacter or H2O over 3-4 weeks then culled. Dura, colons, mesenteric lymph nodes and kidneys were taken to identify transcriptional changes by bulk RNAseq.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005457","title":"KIR gene content imputation from single-nucleotide polymorphisms in the Finnish population","description":"The killer cell immunoglobulin-like receptor (KIR) gene cluster on chromosome 19 encodes cell surface glycoproteins that bind class I human leukocyte antigen (HLA) molecules as well as some other ligands. KIR gene gene copy number variation associates with the outcome of transplantations and susceptibility to immune-mediated diseases. Here we describe a stand-alone and freely available gene content imputation for 12 KIR genes. The models were trained using 818 Finnish biobank samples genotyped for 5774 KIR-region SNPs and analysed for KIR gene content with targeted sequencing.","abstract":"The killer cell immunoglobulin-like receptor (KIR) gene cluster on chromosome 19 encodes cell surface glycoproteins that bind class I human leukocyte antigen (HLA) molecules as well as some other ligands. KIR gene gene copy number variation associates with the outcome of transplantations and susceptibility to immune-mediated diseases. Here we describe a stand-alone and freely available gene content imputation for 12 KIR genes. The models were trained using 818 Finnish biobank samples genotyped for 5774 KIR-region SNPs and analysed for KIR gene content with targeted sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-11T16:09:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005458","title":"A body map of somatic mutagenesis in morphologically normal human tissues (WGS)","description":null,"abstract":"Somatic mutations accumulated in normal tissues are associated with aging and disease. Here, we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies (~ 600 cells each) of nine organs from five donors. We found that somatic mutation accumulations and clonal expansions are widespread, although to variable extents, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for tissues from esophagus and cardia. Endogenous mutational processes like SBS1 and SBS5 are ubiquitous among normal tissues though exhibiting different relative activities. Exogenous mutational processes operate in multiple tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimeter resolution. In esophagus and cardia, macroscopic somatic clones that expanded to hundreds of micrometers were frequently seen, whereas in tissues like colon, rectum, and duodenum, somatic clones were microscopic in size and evolved independently, possibly restricted by local tissue micro-structures. Our study depicted a body map of somatic mutations and clonal expansions from the same individuals, and it revealed that the degree of somatic clonal expansion and enrichment of driver mutations are highly organ specific.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-12T08:18:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005459","title":"A body map of somatic mutagenesis in morphologically normal human tissues (WES)","description":null,"abstract":"Somatic mutations accumulated in normal tissues are associated with aging and disease. Here, we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies (~ 600 cells each), mostly from the epithelia, of nine organs from five donors. We found that somatic mutation accumulations and clonal expansions are widespread, although with variable extent, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for tissues from esophagus and cardia. Endogenous mutational processes like SBS1 and SBS5 are ubiquitous among normal tissues though exhibiting different relative activities. Exogenous mutational processes like SBS22 were found in different tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimeter resolution. In epithelial tissues from esophagus and cardia, macroscopic somatic clones expanded to several millimeters were frequently seen, whereas in tissues from colon, rectum, and duodenum somatic clones were microscopic in size and evolved independently. Our study depicted a body map of somatic mutations and clonal expansions from the same individuals, and it revealed that the degree of somatic clonal expansion and enrichment of driver mutations are highly organ specific.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-12T10:18:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005460","title":"Transcriptome and methylome-wide colorectal cancer association studies","description":null,"abstract":"To augment GWAS discovery, we conducted transcriptome- and methylome-wide association studies (TWAS and MWAS, respectively) by integrating predicted transcriptome and methylome colorectal tissue data from colorectal tissues of 742 participants.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005461","title":"Pre-activated anti-viral innate immunity in the upper airways controls early SARS-CoV-2 infection in children","description":"Children have reduced SARS-CoV-2 infection rates and a substantially lower risk for developing severe COVID-19 than adults. However, the molecular mechanisms underlying protection in younger age groups remain unknown. Here, we characterize the single-cell transcriptional landscape in the upper airways of SARS-CoV-2-negative (n=18) and age-matched SARS-CoV-2–positive children (n=24) and corresponding samples from adults (n=44), covering an age range of four weeks to 77 years. Children displayed higher basal expression of the relevant pattern recognition receptors (PRR) such as  MDA5 (IFIH1) and RIG-I (DDX58) in upper airway epithelial cells, macrophages, and dendritic cells, resulting in stronger innate antiviral responses upon SARS-CoV-2 infection than adults. We further detected distinct immune cell subpopulations including KLRC1 (NKG2A)+ cytotoxic T cells and a CD8+ T cell population with a memory phenotype occurring predominantly in children. Our study provides evidence that the airway immune cells of children are primed for virus sensing, resulting in a stronger early innate antiviral responses to SARS-CoV-2 infection than adults.","abstract":"Children have reduced SARS-CoV-2 infection rates and a substantially lower risk for developing severe COVID-19 than adults. However, the molecular mechanisms underlying protection in younger age groups remain unknown. Here, we characterize the single-cell transcriptional landscape in the upper airways of SARS-CoV-2-negative (n=18) and age-matched SARS-CoV-2–positive children (n=24) and corresponding samples from adults (n=44), covering an age range of four weeks to 77 years. Children displayed higher basal expression of the relevant pattern recognition receptors (PRR) such as  MDA5 (IFIH1) and RIG-I (DDX58) in upper airway epithelial cells, macrophages, and dendritic cells, resulting in stronger innate antiviral responses upon SARS-CoV-2 infection than adults. We further detected distinct immune cell subpopulations including KLRC1 (NKG2A)+ cytotoxic T cells and a CD8+ T cell population with a memory phenotype occurring predominantly in children. Our study provides evidence that the airway immune cells of children are primed for virus sensing, resulting in a stronger early innate antiviral responses to SARS-CoV-2 infection than adults.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-12T13:23:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005462","title":"ChIP-Seq of TFEB in LT-HSC","description":"ChIP-Seq of TFEB in LT-HSC","abstract":"ChIP-Seq of TFEB in LT-HSC","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-12T15:03:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005463","title":"Bruno et al.: Interferon gamma rebalances immunopathological signatures in Chronic Granulomatous Disease through metabolic rewiring","description":"Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by recurrent life-threatening infections and hyperinflammatory complications. It is caused by mutations in the NADPH oxidase complex and the consequent loss of reactive oxygen species (ROS) production. Recombinant human interferon gamma (rIFN-γ) prophylaxis reduces the risk of severe infections, but the mechanisms behind its efficacy in CGD are still an open question, as it does not restore NADPH oxidase-dependent ROS production. Here, we show that myeloid innate immune cells of CGD patients are transcriptionally and functionally reprogrammed to a hyperactive inflammatory status, displaying an impaired in vitro induction of trained immunity. CGD monocytes have reduced intracellular amino acids concentrations and profound functional metabolic defects, both at the level of glycolysis and mitochondrial respiration. Ex vivo and in vivo treatment with IFN-γ restored these metabolic defects and reduced excessive IL-1β and IL-6 production in response to fungal stimuli in CGD monocytes. These data suggest that prophylactic rIFNγ modulates the metabolic status of innate immune cells in CGD. These data shed light on the effects of NADPH-derived ROS deficiency to the metabolic programs of immune cells and pose the basis for targeting this immunometabolic axis, potentially beyond CGD, with IFN-γ immunotherapy.","abstract":"Chronic granulomatous disease (CGD) is a rare inherited immunodeficiency characterized by recurrent life-threatening infections and hyperinflammatory complications (Giardino et al., 2017). It is caused by a mutation in the NADPH oxidase complex and loss of ROS production. r-IFNγ is used in the clinics as prophylaxis for reducing the risk of serious infection but the reason of its efficacy in CGD has been an enigma for decades since it does not restore NADPH-oxidase dependent ROS. Here we show that innate immune cells from CGD patients show a trained immunity status, are epigenetically different, and present an altered in vitro induction of trained immunity compared to healthy controls. CGD monocytes present an intracellular deficit of amino acid and have profound functional metabolic defects, both at the glycolytic and at the mitochondrial level, which are NADPH-oxidase dependent. r-IFNγ restored these defects in CGD cells, providing a novel pathophysiological mechanism of disease in CGD and explains why r-IFNγ prophylaxis has beneficial effects for CGD patients without restoring NADPH-oxidase dependent ROS.","study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005464","title":"Next Generation Sequencing platform for targeted Personalized Therapy of Leukemia - Acute myeloid leukemia","description":"The advent of high-throughput next generation sequencing (NGS) technologies that are revolutionizing genomics and transcriptomics by providing a single base resolution tool for a unified deep analysis of diseases complexity allows a fast and cost-efficient fine-scale assessment of the genetic variability hidden within cohorts of patients affected by the same leukemia. That being so, by potentially highlighting inter-individual differences that may play a role in the differential success of diverse therapeutic interventions, they promise to be crucial for selecting the most appropriate medical treatments. The project aims at the identification of novel prognostic biomarkers for acute myeloid leukemia (AML) and studied the molecular differences between aneuploid and euploid AML.","abstract":"The advent of high-throughput next generation sequencing (NGS) technologies that are revolutionizing genomics and transcriptomics by providing a single base resolution tool for a unified deep analysis of diseases complexity allows a fast and cost-efficient fine-scale assessment of the genetic variability hidden within cohorts of patients affected by the same leukemia. That being so, by potentially highlighting inter-individual differences that may play a role in the differential success of diverse therapeutic interventions, they promise to be crucial for selecting the most appropriate medical treatments. The project aims at the identification of novel prognostic biomarkers for acute myeloid leukemia (AML) and studied the molecular differences between aneuploid and euploid AML.","study_type":"Other","pubmed_ids":[30480765,33414401],"external_links":null,"is_released":true,"released_date":"2021-07-13T15:17:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005465","title":"Multi-omic single-cell profiling of peripheral blood immune cells from COVID-19 patients and controls.","description":"The COVID-19 pandemic, caused by SARS coronavirus 2 (SARS-CoV-2), has resulted in excess morbidity and mortality as well as economic decline. To characterise the systemic host immune response to SARS-CoV-2, we performed single-cell RNA-sequencing coupled with analysis of cell surface proteins, providing molecular profiling of over 800,000 peripheral blood mononuclear cells from a cohort of 130 patients with COVID-19.  Our cohort, from three UK centres, spans the spectrum of clinical presentations and disease severities ranging from asymptomatic to critical. Three control groups were included: healthy volunteers, patients suffering from a non-COVID-19 severe respiratory illness and healthy individuals administered with intravenous lipopolysaccharide to model an acute inflammatory response. Full single cell transcriptomes are coupled with quantification of 188 cell surface proteins, and T and B lymphocyte antigen receptor repertoires.","abstract":"The COVID-19 pandemic, caused by SARS coronavirus 2 (SARS-CoV-2), has resulted in excess morbidity and mortality as well as economic decline. To characterise the systemic host immune response to SARS-CoV-2, we performed single-cell RNA-sequencing coupled with analysis of cell surface proteins, providing molecular profiling of over 800,000 peripheral blood mononuclear cells from a cohort of 130 patients with COVID-19.  Our cohort, from three UK centres, spans the spectrum of clinical presentations and disease severities ranging from asymptomatic to critical. Three control groups were included: healthy volunteers, patients suffering from a non-COVID-19 severe respiratory illness and healthy individuals administered with intravenous lipopolysaccharide to model an acute inflammatory response. Full single cell transcriptomes are coupled with quantification of 188 cell surface proteins, and T and B lymphocyte antigen receptor repertoires.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-14T10:47:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005466","title":"IMCISION DNAseq","description":"Standard-of-care (SOC) surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) is intensive and results in 30‒50% five-year overall survival. Anti-PD1 immune checkpoint blockade (ICB) durably improves survival rates in recurrent/metastatic HNSCC. We report on the non-randomized phase Ib/IIa IMCISION trial (NCT03003637) of 32 HNSCC patients treated with two doses neoadjuvant nivolumab (NIVO MONO, n=6, phase Ib arm A) or two doses of nivolumab plus a single dose of ipilimumab (COMBO, n=26, 6 in phase Ib arm B and 20 in phase IIa) prior to surgery and, if indicated, adjuvant radiotherapy. Neoadjuvant ICB was feasible in all phase Ib patients, meeting the phase Ib primary feasibility endpoint. One phase IIa patient had progressive disease precluding surgery. Primary tumor pathological response (phase IIa primary endpoint), defined as the % change in viable tumor cells from baseline biopsy to on-treatment resection, was evaluable in 29 patients. . We observed a major pathological response (MPR, 90‒100% response) in 8/23 (35%) evaluable COMBO and 1/6 (17%) NIVO MONO patients. None of the patients with MPR after NIVO MONO or COMBO developed a tumor relapse after 24.0 months median follow-up. FDG-PET-based total lesion glycolysis identified MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia signature expression were observed in MPR patients. Our data indicate that neoadjuvant NIVO MONO and COMBO are safe in HNSCC, and that particularly COMBO ICB shows encouraging effectivity. IMCISION provides rationales for future HNSCC trials aiming to pre-operatively select patients with a likely MPR after neoadjuvant ICB for de-escalation of SOC.","abstract":"Standard-of-care (SOC) surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) is intensive and results in 30‒50% five-year overall survival. Anti-PD1 immune checkpoint blockade (ICB) durably improves survival rates in recurrent/metastatic HNSCC. We report on the non-randomized phase Ib/IIa IMCISION trial (NCT03003637) of 32 HNSCC patients treated with two doses neoadjuvant nivolumab (NIVO MONO, n=6, phase Ib arm A) or two doses of nivolumab plus a single dose of ipilimumab (COMBO, n=26, 6 in phase Ib arm B and 20 in phase IIa) prior to surgery and, if indicated, adjuvant radiotherapy. Neoadjuvant ICB was feasible in all phase Ib patients, meeting the phase Ib primary feasibility endpoint. One phase IIa patient had progressive disease precluding surgery. Primary tumor pathological response (phase IIa primary endpoint), defined as the % change in viable tumor cells from baseline biopsy to on-treatment resection, was evaluable in 29 patients. . We observed a major pathological response (MPR, 90‒100% response) in 8/23 (35%) evaluable COMBO and 1/6 (17%) NIVO MONO patients. None of the patients with MPR after NIVO MONO or COMBO developed a tumor relapse after 24.0 months median follow-up. FDG-PET-based total lesion glycolysis identified MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia signature expression were observed in MPR patients. Our data indicate that neoadjuvant NIVO MONO and COMBO are safe in HNSCC, and that particularly COMBO ICB shows encouraging effectivity. IMCISION provides rationales for future HNSCC trials aiming to pre-operatively select patients with a likely MPR after neoadjuvant ICB for de-escalation of SOC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-15T07:44:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005467","title":"Whole-genome sequencing of INSIGHT-HD BMF/MDS cohort","description":"Bone marrow failure (BMF) and myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies, and their germline predisposition has long been recognized. However, a battery of assays is currently required to diagnose patients with inherited BMF/MDS predisposition syndromes. Here, we implemented Whole-genome sequencing (WGS) based all-in-one approach for rapid diagnosis of and stratification of the INSIGHT-HD BMF/MDS cohort at St Jude, including 77 patients and 17 healthy individuals. Using our WGS approach, we identified all previously known germline lesions screened by traditional methods in 46 known cases, as well as novel findings in six unknown cases. We also established a pipeline for the estimation of short telomere length in pediatric patients. WGS is a promising platform for comprehensive and efficient genetic diagnosis of BMF and MDS.","abstract":"Bone marrow failure (BMF) and myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies, and their germline predisposition has long been recognized. However, a battery of assays is currently required to diagnose patients with inherited BMF/MDS predisposition syndromes. Here, we implemented Whole-genome sequencing (WGS) based all-in-one approach for rapid diagnosis of and stratification of the INSIGHT-HD BMF/MDS cohort at St Jude, including 77 patients and 17 healthy individuals. Using our WGS approach, we identified all previously known germline lesions screened by traditional methods in 46 known cases, as well as novel findings in six unknown cases. We also established a pipeline for the estimation of short telomere length in pediatric patients. WGS is a promising platform for comprehensive and efficient genetic diagnosis of BMF and MDS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005468","title":"An epigenomics time course analysis of covid19 patients from Quebec, Canada","description":"Investigating the cellular and epigenetic changes at play in severely ill hospitalized COVID-19 patients at admission and how it evolves with prognosis. Single-cell RNA-seq analysis done on longitudinal samples highlighted changes in the monocytic compartment, which we explored using whole-genome epigenomics methods (ATACseq abd WGBS).","abstract":"Investigating the cellular and epigenetic changes at play in severely ill hospitalized COVID-19 patients at admission and how it evolves with prognosis. Single-cell RNA-seq analysis done on longitudinal samples highlighted changes in the monocytic compartment, which we explored using whole-genome epigenomics methods (ATACseq abd WGBS).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-16T17:30:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005469","title":"Differential expression profile of gluten-specific T cells identified by single-cell RNA-seq","description":"Gluten-specific CD4+ T cells drive the pathogenesis of celiac disease and circulating gluten-specific T cells can be identified by staining with HLA-DQ:gluten tetramers. In this first single-cell RNA-seq study of tetramer-sorted T cells from untreated celiac disease patients blood, we found that gluten-specific T cells showed distinct transcriptomic profiles consistent with activated effector memory T cells that shared features with Th1 and follicular helper T cells. Compared to non-specific cells, gluten-specific T cells showed differential expression of several genes involved in T-cell receptor signaling, translational processes, apoptosis, fatty acid transport, and redox potentials. Many of the gluten-specific T cells studied shared T-cell receptor with each other, indicating that circulating gluten-specific T cells belong to a limited number of clones. Moreover, the transcriptional profiles of cells that shared the same clonal origin were transcriptionally more similar compared with between clonally unrelated gluten-specific cells.","abstract":"Gluten-specific CD4+ T cells drive the pathogenesis of celiac disease and circulating gluten-specific T cells can be identified by staining with HLA-DQ:gluten tetramers. In this first single-cell RNA-seq study of tetramer-sorted T cells from untreated celiac disease patients blood, we found that gluten-specific T cells showed distinct transcriptomic profiles consistent with activated effector memory T cells that shared features with Th1 and follicular helper T cells. Compared to non-specific cells, gluten-specific T cells showed differential expression of several genes involved in T-cell receptor signaling, translational processes, apoptosis, fatty acid transport, and redox potentials. Many of the gluten-specific T cells studied shared T-cell receptor with each other, indicating that circulating gluten-specific T cells belong to a limited number of clones. Moreover, the transcriptional profiles of cells that shared the same clonal origin were transcriptionally more similar compared with between clonally unrelated gluten-specific cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005470","title":"Genome sequencing of childhood acute leukemia in Iraq","description":"Mutations in acute leukemia vary among countries. To obtain a catalog of mutations of acute leukemia in Iraq, we performed a next-generation sequencing study of childhood acute lymphoblastic and myeloid leukemia. We performed whole-genome sequencing or a combination of whole-exome sequencing to identify somatic and germline mutations + targeted sequencing to identify gene fusions.","abstract":"Mutations in acute leukemia vary among countries. To obtain a catalog of mutations of acute leukemia in Iraq, we performed a next-generation sequencing study of childhood acute lymphoblastic and myeloid leukemia. We performed whole-genome sequencing or a combination of whole-exome sequencing to identify somatic and germline mutations + targeted sequencing to identify gene fusions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-19T11:03:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005471","title":"Genomic_landscape_of_liver_cirrhosis___methylation","description":"This is a pilot project to assess the methylation landscape of liver cirrhosis. Non-cancer cirrhotic liver tissue biopsies will undergo LCM to look for clonality and methylation changes across the entire liver and focusing on cancer genes. Furthermore this will be compared to the linked study on mutations in liver cirrhosis.\n\nThis is linked to the study \"Genomic landscape of liver cirrhosis\" and will complement the genomic data already generated. In particular, we have identified driver mutations which we will explore by assessing the methylation status across the genome in clones with and without those mutations.","abstract":"This is linked to the study \"Genomic landscape of liver cirrhosis\" and will complement the genomic data already generated. In particular, we have identified driver mutations which we will explore by assessing the methylation status across the genome in clones with and without those mutations.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005472","title":"Epigenetic encoding, heritability and plasticity of glioma transcriptional cell states","description":null,"abstract":"Single cell RNA-sequencing revealed extensive transcriptional cell state diversity in cancer, often observed independently from genetic heterogeneity, raising the central question of how malignant cell states are encoded epigenetically. To address this, we performed multi-omics single-cell profiling – integrating DNA methylation, transcriptome, and genotyping within the same cells – of diffuse gliomas, tumors governed by defined transcriptional cell state diversity. Direct comparison of the epigenetic profiles of distinct cell states revealed key switches for state transitions recapitulating neurodevelopmental trajectories, and highlighted dysregulated epigenetic mechanisms underlying gliomagenesis. We further developed a quantitative framework to measure cell state heritability and transition dynamics based on high resolution lineage trees directly in human samples. We demonstrated heritability of malignant cell states, with key differences in hierarchal vs. plastic cell state architectures in IDH-mutant glioma vs. IDH-wildtype glioblastoma, respectively. This work provides a novel framework anchoring transcriptional cancer cell states in their epigenetic encoding, inheritance and transition dynamics.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-20T19:20:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005473","title":"Genotyping and sequencing study of lung carcinoid tumours","description":null,"abstract":"Lung Carcinoids (LCARs) are uncommon low-grade neuroendocrine tumours that are poorly characterised at the molecular level. We describe here a comprehensive characterization of these malignancies at the molecular level using DNA genotyping, sequencing and transcriptomics complemented by query of DNA methylation levels through whole-genome bisulphite sequencing.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005474","title":"Integrative analysis of genomic, transcriptomic and drug response data for pancreatic ductal adenocarcinoma using patient-derived organoids (HIPO K20K, XI055)","description":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis and refractory to treatment. Surgical resection followed by adjuvant chemotherapy is the best therapeutic option for patients with resectable disease, however, predictive biomarkers of efficacy are scarce and only a reduce percentage offew patients reach 5-year survival. Identification of new therapeutic and stratification strategies are therefore urgently needed. Here we present a catalogue of 51 PDAC patient-derived tumor organoids (PDAC-PDTOs) derived from resected patients for which we performed integrative analyses based on molecular, drug response and clinical data.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005475","title":"Sequence data for study: Mobilization of tissue-resident memory CD4+ T lymphocytes from bone marrow and their contribution to a systemic secondary immune reaction","description":"Resident memory T lymphocytes (TRM) of epithelial tissues and the bone marrow protect their host tissue. To what extent these cells are mobilized and contribute to systemic immune reactions is less clear. Here we show that in secondary immune reactions to the measles-mumps-rubella (MMR) vaccine, CD4+ TRM are mobilized into the blood within 16 to 48 hours after immunization. This mobilization of TRM is cognate: TRM recognizing other antigens are not mobilized, unless they cross-react with the vaccine. We also demonstrate through methylome analyses that TRM are mobilized from the bone marrow. These mobilized cells make significant contribution to the systemic immune reaction, as evidenced by their T-cell receptor Vβ clonotypes represented among the newly generated circulating memory T-cells, 14 days after vaccination. Thus, TRM of the bone marrow confer not only local, but also systemic immune memory.","abstract":"Resident memory T lymphocytes (TRM) of epithelial tissues and the bone marrow protect their host tissue. To what extent these cells are mobilized and contribute to systemic immune reactions is less clear. Here we show that in secondary immune reactions to the measles-mumps-rubella (MMR) vaccine, CD4+ TRM are mobilized into the blood within 16 to 48 hours after immunization. This mobilization of TRM is cognate: TRM recognizing other antigens are not mobilized, unless they cross-react with the vaccine. We also demonstrate through methylome analyses that TRM are mobilized from the bone marrow. These mobilized cells make significant contribution to the systemic immune reaction, as evidenced by their T-cell receptor Vβ clonotypes represented among the newly generated circulating memory T-cells, 14 days after vaccination. Thus, TRM of the bone marrow confer not only local, but also systemic immune memory.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-21T15:12:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005476","title":"TULIPs decorate the three-dimensional genome of PFA ependymoma","description":null,"abstract":"Identifying aberrant genome architecture in pediatric brain tumors that present few genetic changes.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-22T00:34:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005477","title":"Microarray Markers of Response","description":null,"abstract":"Transcriptomic predictors of response to anti-PD1 are unknown in patients with hepatocellular carcinoma (HCC). Here, we performed genomic profiling of tumor samples from patients treated with anti-PD1 in either front- or 2nd/3rd line.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-22T10:43:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005478","title":"The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma","description":"Patients with metastatic uveal melanoma (UM) have an abysmal prognosis. Preclinical studies have suggested that epigenetic therapy could enhance immunogenicity of cancer cells. Here we test if epigenetic therapy would enhance PD-1 immunotherapy in patients with metastatic UM. We report the results of the PEMDAC phase 2 clinical trial (n=29; NCT02697630) where the HDAC inhibitor entinostat was combined with the PD-1 inhibitor pembrolizumab in  patients with metastatic UM. The primary endpoint was objective response rate (ORR), and was met with an ORR of 14%. The clinical benefit rate at 18 weeks was 28%, median progression free survival was 2.1 months and the median overall survival was 13.4 months. Toxicities were manageable, and there were no treatment-related deaths. Extensive genomics studies were performed using DNA/RNA and single cell sequencing and flow cytometry. Objective responses and prolonged survival were seen in three patients with BAP1 wildtype tumors, and in one patient with an iris melanoma that exhibited a UV signature. Longer survival also correlated with low baseline ctDNA levels or LDH. In conclusion, HDAC inhibition and anti-PD1 immunotherapy results in durable responses in a subset of patients with metastatic UM. Further exploration of combined immunotherapy and epigenetic therapy in metastatic UM is warranted.","abstract":"Patients with metastatic uveal melanoma (UM) have an abysmal prognosis. Preclinical studies have suggested that epigenetic therapy could enhance immunogenicity of cancer cells. Here we test if epigenetic therapy would enhance PD-1 immunotherapy in patients with metastatic UM. We report the results of the PEMDAC phase 2 clinical trial (n=29; NCT02697630) where the HDAC inhibitor entinostat was combined with the PD-1 inhibitor pembrolizumab in  patients with metastatic UM. The primary endpoint was objective response rate (ORR), and was met with an ORR of 14%. The clinical benefit rate at 18 weeks was 28%, median progression free survival was 2.1 months and the median overall survival was 13.4 months. Toxicities were manageable, and there were no treatment-related deaths. Extensive genomics studies were performed using DNA/RNA and single cell sequencing and flow cytometry. Objective responses and prolonged survival were seen in three patients with BAP1 wildtype tumors, and in one patient with an iris melanoma that exhibited a UV signature. Longer survival also correlated with low baseline ctDNA levels or LDH. In conclusion, HDAC inhibition and anti-PD1 immunotherapy results in durable responses in a subset of patients with metastatic UM. Further exploration of combined immunotherapy and epigenetic therapy in metastatic UM is warranted.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-23T05:52:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005479","title":"Multi-omics analysis of serial samples from metastatic TNBC patients on PARP inhibitor monotherapy provide insight into rational PARP inhibitor therapy combinations","description":"In a pilot study, we evaluated the safety and efficacy of olaparib/durvalumab combination treatment in mTNBC patients and the feasibility of real-time deep analysis of serial tumor samples from triple negative breast cancer patients to identify mechanisms of resistance and treatment opportunities. This study used the SMMART analytic platform at OHSU KCI and incorporated comprehensive multi-omic analysis of serial liquid and tumor biopsies. Deep analysis of longitudinal biopsies combined with a robust computational biology pipeline identified multiple PARPi-induced changes in immune activation, DNA damage checkpoint activation, apoptosis and signaling pathways including RTK, PI3K-AKT and RAS-MAPK. These emergent tumor and immune state changes could act as biomarker targets to be used in selecting patient specific combination therapies.","abstract":"In a pilot study, we evaluated the safety and efficacy of olaparib/durvalumab combination treatment in mTNBC patients and the feasibility of real-time deep analysis of serial tumor samples from triple negative breast cancer patients to identify mechanisms of resistance and treatment opportunities. This study used the SMMART analytic platform at OHSU KCI and incorporated comprehensive multi-omic analysis of serial liquid and tumor biopsies. Deep analysis of longitudinal biopsies combined with a robust computational biology pipeline identified multiple PARPi-induced changes in immune activation, DNA damage checkpoint activation, apoptosis and signaling pathways including RTK, PI3K-AKT and RAS-MAPK. These emergent tumor and immune state changes could act as biomarker targets to be used in selecting patient specific combination therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-23T20:03:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005480","title":"Analysis of T-cell receptor clonotypes in tumor micro-environment identifies  shared cancer type-specific signatures","description":"Despite the conventional view that a truly random V(D)J recombination process should generate a highly diverse immune repertoire, emerging reports suggest that there is a certain bias towards the generation of shared/public immune receptor chains. These studies were performed in viral diseases where public T-cell receptors (TCR) appear to confer better protective responses. Selective pressures generating common TCR clonotypes are currently not well understood but it is believed that they confer a growth advantage. As very little is known about public TCR clonotypes in cancer, here we set out to determine the extent of shared TCR clonotypes in the intra-tumor microenvironments of virus- and non-virus- driven head and neck cancers using TCR sequencing. We report that tumor-infiltrating T-cell clonotypes were indeed shared across individuals with the same cancer type, where the majority of shared sequences were specific to the cancer type (ie viral versus non-viral). These shared clonotypes were not particularly enriched in EBV-associated nasopharynx cancer, but in both cancers, exhibited distinct characteristics, namely shorter CDR3 lengths, restricted V- and J-gene usages and also demonstrated convergent V(D)J recombination. Many of these shared TCRs were expressed in patients with a shared HLA background. Pattern recognition of CDR3 amino acid sequences revealed strong convergence to specific motifs that were unique to each cancer type, suggesting they may be enriched for specificity to common antigens found in the tumor microenvironment. The identification of shared TCRs in infiltrating tumor T-cells not only adds to our understanding of the tumor adaptive immune recognition but could also serve as disease-specific biomarkers and guide the development of future immunotherapies.","abstract":"Despite the conventional view that a truly random V(D)J recombination process should generate a highly diverse immune repertoire, emerging reports suggest that there is a certain bias towards the generation of shared/public immune receptor chains. These studies were performed in viral diseases where public T-cell receptors (TCR) appear to confer better protective responses. Selective pressures generating common TCR clonotypes are currently not well understood but it is believed that they confer a growth advantage. As very little is known about public TCR clonotypes in cancer, here we set out to determine the extent of shared TCR clonotypes in the intra-tumor microenvironments of virus- and non-virus- driven head and neck cancers using TCR sequencing. We report that tumor-infiltrating T-cell clonotypes were indeed shared across individuals with the same cancer type, where the majority of shared sequences were specific to the cancer type (ie viral versus non-viral). These shared clonotypes were not particularly enriched in EBV-associated nasopharynx cancer, but in both cancers, exhibited distinct characteristics, namely shorter CDR3 lengths, restricted V- and J-gene usages and also demonstrated convergent V(D)J recombination. Many of these shared TCRs were expressed in patients with a shared HLA background. Pattern recognition of CDR3 amino acid sequences revealed strong convergence to specific motifs that were unique to each cancer type, suggesting they may be enriched for specificity to common antigens found in the tumor microenvironment. The identification of shared TCRs in infiltrating tumor T-cells not only adds to our understanding of the tumor adaptive immune recognition but could also serve as disease-specific biomarkers and guide the development of future immunotherapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-26T12:46:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005481","title":"Whole_exome_sequencing_of_paediatric_IBD_patients","description":"Whole-exome sequencing of paediatric IBD patients","abstract":"The Sanger Institute will combine the sequence data with clinical and demographic data relating to the patients (supplied by Dr. Zilbauer) to identify genetic variants underpinning IBD susceptibility, prognosis, onset or drug-response. These studies may make singular use of the sequencing and phenotypic data or in combination with other similar datasets generated on additional samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005482","title":"Non-small cell lung cancer proteome subtypes expose targetable oncogenic drivers and immune evasion mechanisms","description":"Proteome-level data of non-small cell lung cancer remains limited. In this study, we have collected 141 cases, and performed histological review, methylation profiling (113), custom panel sequencing (140), microarray expression profiling (118) and mass-spectrometry based proteomics (141). We identified six distinct groups of patients driven by histology, growth pattern, immune cell infiltration, druggable driver mutations, and hypomethylation-associated neoantigen burden. We validated the subtypes in independent proteomics datasets. Proteomics can refine treatment-oriented subtyping of non-small cell lung cancer.","abstract":"Proteome-level data of non-small cell lung cancer remains limited. In this study, we have collected 141 cases, and performed histological review, methylation profiling (113), custom panel sequencing (140), microarray expression profiling (118) and mass-spectrometry based proteomics (141). We identified six distinct groups of patients driven by histology, growth pattern, immune cell infiltration, druggable driver mutations, and hypomethylation-associated neoantigen burden. We validated the subtypes in independent proteomics datasets. Proteomics can refine treatment-oriented subtyping of non-small cell lung cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-26T14:04:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005483","title":"MM.1S H3K27ac Chromatin Immunoprecipitation followed by high-throughput sequencing","description":null,"abstract":"Chromatin Immunoprecipitation with H3K27ac antibody were performed in MM.1S cells with two conditions (Dex and EtOH 1 hour)","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005484","title":"MM.1S GR Chromatin Immunoprecipitation followed by high-throughput sequencing","description":null,"abstract":"Chromatin Immunoprecipitation with GR antibody were performed in MM.1S cells with two conditions (Dex and EtOH 1 hour)","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005485","title":"MM.1S H3K27ac Chromatin Immunoprecipitation combined with conformation capture and followed by high-throughput sequencing","description":null,"abstract":"H3K27ac chromatin immunprecipitation combined with chromosome conformation capture were performed for MM.1S cells in two conditions (Dex and EtOH 1h). For each condition, data were generated with two technical replicates","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005486","title":"MM.1S Chromatin Immunoprecipitation followed by high-throughput sequencing","description":null,"abstract":"Chromatin Immunoprecipitation with CTCF, GR or H3K27ac antibody were performed in MM.1S cell line with two conditions (Dex and EtOH 1 hour)","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005487","title":"MM.1S RNA-seq Transcriptome analysis","description":null,"abstract":"RNA-seq bulk performed in two conditions (Dex and EtOH 4h), both performed with three technical replicates","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005488","title":"MM.1S Single Cell Multiome (ATAC + Gene Expression)","description":null,"abstract":"Single Cell Multiome combining Single cell 3' gene expression and open chromatin librairies generation were performed in two conditions (Dex and EtOH) at two different time points (1h and 4h)","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-27T09:13:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005489","title":"MM.1S Single Cell Transcriptome Analysis","description":null,"abstract":"Single Cell were performed for MM.1S Cell lines in two conditions (Dex and EtOH) and at two different time points (4hour and 24hour)","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005490","title":"MM.1S Chromatin Accessibility combined with high-throughpout sequencing","description":null,"abstract":"chromatin accessibility assay for MM.1S performed with Fast-ATAC protocol. Two conditions Dex and EtOH (1 hour)","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005491","title":"MM.1S Chromatin Immunoprecipitation combined with chromosome conformation capture and followed by high-throughput sequencing","description":null,"abstract":"HiChIP protocol were performed in MM.1S cell line treated with EtOH (control) or Dexamethasone (treatment), chromatin immunoprecipitation were performed using H3K27ac antibody.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005492","title":"COVID_19_UK_CIC","description":"Understanding the immune response to SARS-CoV-2.","abstract":"Understanding the immune response to SARS-CoV-2 is critical to our ability to control the coronavirus pandemic. Single cell sequencing will be performed on PBMCs isolated from Covid-19 positive patients (75% BAME population) in collaboration with the UK - Coronavirus immunology consortium (UK-CIC). UK-CIC sees the UK's world-leading immunology community deliver a co-ordinated and agile national research programme to increase our understanding of how the immune system interacts with SARS-CoV-2. UK-CIC is led by Professor Paul Moss (University of Birmingham) and brings together 20 UK immunology centres of excellence, with support from the British Society for Immunology.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005493","title":"A blood atlas of COVID-19 defines hallmarks of disease severity and specificity","description":"Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete understanding of potentially druggable immune mediators of disease. To advance this, we present a comprehensive multi-omic blood atlas in patients with varying COVID-19 severity and compare with influenza, sepsis and healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity revealed cells, their inflammatory mediators and networks as potential therapeutic targets, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Tensor and matrix decomposition of the overall dataset revealed feature groupings linked with disease severity and specificity. Our systems-based integrative approach and blood atlas will inform future drug development, clinical trial design and personalised medicine approaches for COVID-19.","abstract":"Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete understanding of potentially druggable immune mediators of disease. To advance this, we present a comprehensive multi-omic blood atlas in patients with varying COVID-19 severity and compare with influenza, sepsis and healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity revealed cells, their inflammatory mediators and networks as potential therapeutic targets, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Tensor and matrix decomposition of the overall dataset revealed feature groupings linked with disease severity and specificity. Our systems-based integrative approach and blood atlas will inform future drug development, clinical trial design and personalised medicine approaches for COVID-19.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-27T09:06:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005494","title":"Characterizing_the_methylome_of_human_bronchial_epithelium","description":"This study aims to characterize the epigenetic landscape of single-cell derived colonies from lung tissue of normal epithelium with various smoking histories. Single-cell colonies have been created from patients that underwent broncoscopy. These samples have previously been profiled using whole genome sequencing. The results of this have been published by Yoshida and colleagues (https://www.nature.com/articles/s41586-020-1961-1/). Here, we will follow-up on this work by characterizing colonies with known mutation burden in order to assess the the influence of high, tobacco-associated mutation burden on the epigenome.  In addition, we will assess differentially methylated regions in colonies with high and near-normal mutation burden to increase our understanding of the epigenetic heterogeneity in normal lung tissue.","abstract":"This study aims to characterize the epigenetic landscape of single-cell derived colonies from lung tissue of normal epithelium with various smoking histories. Single-cell colonies have been created from patients that underwent broncoscopy. These samples have previously been profiled using whole genome sequencing. The results of this have been published by Yoshida and colleagues (https://www.nature.com/articles/s41586-020-1961-1/). Here, we will follow-up on this work by characterizing colonies with known mutation burden in order to assess the the influence of high, tobacco-associated mutation burden on the epigenome.  In addition, we will assess differentially methylated regions in colonies with high and near-normal mutation burden to increase our understanding of the epigenetic heterogeneity in normal lung tissue.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005495","title":"Multi-omics of Richter syndrome","description":"Richter syndrome (RS) is the aggressive transformation of Chronic Lymphocytic Leukemia, mostly with Diffuse Large B-Cell Lymphoma histology. While histologically similar, RS and de novo DLBCLs present with different clinical courses. We characterized the RS epigenome by combining genome-wide DNA methylation with transcriptome-sequencing on a large RS cohort.","abstract":"Richter syndrome (RS) is the aggressive transformation of Chronic Lymphocytic Leukemia, mostly with Diffuse Large B-Cell Lymphoma histology. While histologically similar, RS and de novo DLBCLs present with different clinical courses. We characterized the RS epigenome by combining genome-wide DNA methylation with transcriptome-sequencing on a large RS cohort.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-27T16:13:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005496","title":"Correction of a Factor VIII genomic inversion with designer recombinases","description":"Despite advances in nuclease-based genome editing technologies, correcting human disease-causing genomic inversions remains a challenge. Here, we describe the potential use of a recombinase-based system to correct the 140 kb inversion of the F8 gene frequently found in patients diagnosed with severe Hemophilia A. Employing substrate-linked directed molecular evolution, we developed a coupled heterodimeric recombinase system (RecF8) achieving 30% inversion of the target sequence in human tissue culture cells. Transient RecF8 treatment of endothelial cells, differentiated from patient derived induced pluripotent stem cells (iPSCs) of a hemophilic donor, resulted in 12% correction of the inversion and restored Factor VIII mRNA expression. Our data suggests that designer-recombinases may represent efficient and specific means towards treatment of monogenic diseases caused by large gene inversions.","abstract":"Despite advances in nuclease-based genome editing technologies, correcting human disease-causing genomic inversions remains a challenge. Here, we describe the potential use of a recombinase-based system to correct the 140 kb inversion of the F8 gene frequently found in patients diagnosed with severe Hemophilia A. Employing substrate-linked directed molecular evolution, we developed a coupled heterodimeric recombinase system (RecF8) achieving 30% inversion of the target sequence in human tissue culture cells. Transient RecF8 treatment of endothelial cells, differentiated from patient derived induced pluripotent stem cells (iPSCs) of a hemophilic donor, resulted in 12% correction of the inversion and restored Factor VIII mRNA expression. Our data suggests that designer-recombinases may represent efficient and specific means towards treatment of monogenic diseases caused by large gene inversions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-27T18:51:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005497","title":"DNA  methylation  calling  tools  for  Oxford  Nanopore  sequencing:  a survey and human epigenome-wide evaluation","description":null,"abstract":"We compare methylation calling tools for detecting DNA modification from Nanopore long-read sequencing data. Our study is the first benchmark of computational methods for mammalian whole genome DNA-modification detection in Nanopore sequencing. We provide a broad foundation for cross-platform standardization and an evaluation of analytical tools designed for genome-scale modified-base detection using nanopore sequencing.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005498","title":"Unraveling the transcriptomic profile of utero-tubal lavage fluid of ovarian cancer patients","description":"The majority of ovarian cancers are diagnosed at an advanced stage and have a high mortality rate. Current screening strategies fail to improve prognosis because markers of early stage disease are lacking. This medical need justifies the search for biomarkers enabling early detection of ovarian cancer. In this study, we explore the extracellular transcriptome of utero-tubal lavage fluid obtained from 26 ovarian cancer patients and 48 controls using messenger RNA (mRNA) capture and small RNA sequencing. Because of its contact with the fallopian tube and the ovaries, collection of utero-tubal lavage might be the preferred non-invasive method to identify localized lesions compared with analyses based on peripheral blood samples. We observed an enrichment of ovarian and fallopian tube specific messenger RNAs in utero-tubal lavage fluid compared to other human biofluids. Over 300 mRNAs and 41 miRNAs were upregulated in ovarian cancer samples compared with controls. Upregulated genes were enriched for genes involved in cell cycle activation and proliferation, hinting at a tumor derived signal. In conclusion, we provide proof-of-principle that mRNA capture sequencing of utero-tubal lavage fluid is technically feasible, and that the extracellular transcriptome of utero-tubal lavage should be further explored in larger cohorts to assess the diagnostic value of the biomarkers identified in this study.","abstract":"The majority of ovarian cancers are diagnosed at an advanced stage and have a high mortality rate. Current screening strategies fail to improve prognosis because markers of early stage disease are lacking. This medical need justifies the search for biomarkers enabling early detection of ovarian cancer. In this study, we explore the extracellular transcriptome of utero-tubal lavage fluid obtained from 26 ovarian cancer patients and 48 controls using messenger RNA (mRNA) capture and small RNA sequencing. Because of its contact with the fallopian tube and the ovaries, collection of utero-tubal lavage might be the preferred non-invasive method to identify localized lesions compared with analyses based on peripheral blood samples. We observed an enrichment of ovarian and fallopian tube specific messenger RNAs in utero-tubal lavage fluid compared to other human biofluids. Over 300 mRNAs and 41 miRNAs were upregulated in ovarian cancer samples compared with controls. Upregulated genes were enriched for genes involved in cell cycle activation and proliferation, hinting at a tumor derived signal. In conclusion, we provide proof-of-principle that mRNA capture sequencing of utero-tubal lavage fluid is technically feasible, and that the extracellular transcriptome of utero-tubal lavage should be further explored in larger cohorts to assess the diagnostic value of the biomarkers identified in this study.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-28T14:21:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005499","title":"Non-small cell lung cancer sequencing","description":null,"abstract":"For neoantigen discovery in non-small cell lung cancer, whole exome sequencing and RNAseq was performed on 15 adenocarcinoma and 9 squamous cell carcinoma patients. The raw sequencing data is deposited here. DNA and RNA were extracted from tumour tissue that had been obtained fresh and immediately snap frozen in liquid nitrogen. Germline DNA and RNA were extracted from autologous PBMC.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-28T14:44:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005500","title":"Comprehensive genomic profile of sporadic multiple meningiomas and identification of clonal formation patterns","description":null,"abstract":"While the genomic background of familial multiple meningiomas with germline mutations is well studied, the molecular understanding for sporadic multiple meningiomas remains understudied and with limitations, where the etiology is thought to be either monoclonal or independent formation. \nWe performed whole exome sequencing of 13 meningiomas and one dura specimen, obtained from five individuals with no familial history of meningioma or prior radiation therapy. The comparative somatic genomic profile for all tumors, as compared to the matching blood samples, were analyzed and integrated with detailed clinical information. Tumor formation patterns were inferred and represented with phylogenies.We found sporadic multiple meningiomas can emerge through either monoclonal expansion or independent formation. Our study underscores the need for the comprehensive genomic profiling of multiple sporadic meningiomas given the complexity of these tumors and potential differences in their biology and behavior.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005501","title":"CM214 - Biomarker Analysis From the Phase 3 CheckMate 214 Trial of Nivolumab Plus Ipilimumab (N+I) or Sunitinib (S) in Advanced Renal Cell Carcinoma (aRCC)","description":"CM214 - Biomarker Analysis From the Phase 3 CheckMate 214 Trial of Nivolumab Plus Ipilimumab (N+I) or Sunitinib (S) in Advanced Renal Cell Carcinoma (aRCC)","abstract":"CM214 - Biomarker Analysis From the Phase 3 CheckMate 214 Trial of Nivolumab Plus Ipilimumab (N+I) or Sunitinib (S) in Advanced Renal Cell Carcinoma (aRCC)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-29T05:21:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005502","title":"Embryonal Rhabdomyosarcoma sequencing data","description":"This study shares DNA and RNA sequencing data from embryonal rhadbomyosarcoma patients","abstract":"This study shares DNA and RNA sequencing data from embryonal rhadbomyosarcoma patients","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-29T18:30:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005503","title":"Integrated genomic analyses reveal molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma","description":"Atezolizumab (anti–programmed death-ligand 1 [anti-PD-L1]) and bevacizumab (anti-vascular endothelial growth factor [anti-VEGF]) combination therapy has become the new standard of care in patients with unresectable hepatocellular carcinoma. However, potential predictive biomarkers and mechanisms of response and resistance remain less understood. We report integrated molecular analyses of tumor samples from 358 patients enrolled in the GO30140 phase 1b or IMbrave150 phase 3 trials who were treated with atezolizumab combined with bevacizumab, atezolizumab alone, or sorafenib. Pre-existing immunity assessed by high expression of CD274 (PD-L1 mRNA), T-effector signature, and intratumoral CD8+ T cell density were associated with response and better clinical outcomes with the combination treatment. Less clinical benefit was associated with high regulatory T cell (Treg) to effector T-cell ratio and high expression of oncofetal genes such as GPC3 and AFP. Improved outcomes from the combination vs atezolizumab alone appeared to be associated with high expression of KDR (VEGFR2), Treg, and myeloid inflammation signatures, indicating anti-VEGF may contribute by targeting these axes. These findings were further validated by transcriptome analysis of paired pre- and post-treatment biopsies, in situ analysis by multiplex IHC and digital pathology, and in vivo study of an immunogenic hepatocellular carcinoma mouse model. Our findings highlight that anti-VEGF therapy might augment antitumor immunity and enhance anti–PD-L1 immunotherapy by targeting VEGF-mediated angiogenesis, Treg proliferation, and myeloid cell inflammation. Furthermore, our study identified candidate biomarkers for predicting response and resistance to anti–PD-L1 and anti-VEGF combination therapy.","abstract":"Atezolizumab (anti–programmed death-ligand 1 [anti-PD-L1]) and bevacizumab (anti-vascular endothelial growth factor [anti-VEGF]) combination therapy has become the new standard of care in patients with unresectable hepatocellular carcinoma. However, potential predictive biomarkers and mechanisms of response and resistance remain less understood. We report integrated molecular analyses of tumor samples from 358 patients enrolled in the GO30140 phase 1b or IMbrave150 phase 3 trials who were treated with atezolizumab combined with bevacizumab, atezolizumab alone, or sorafenib. Pre-existing immunity assessed by high expression of CD274 (PD-L1 mRNA), T-effector signature, and intratumoral CD8+ T cell density were associated with response and better clinical outcomes with the combination treatment. Less clinical benefit was associated with high regulatory T cell (Treg) to effector T-cell ratio and high expression of oncofetal genes such as GPC3 and AFP. Improved outcomes from the combination vs atezolizumab alone appeared to be associated with high expression of KDR (VEGFR2), Treg, and myeloid inflammation signatures, indicating anti-VEGF may contribute by targeting these axes. These findings were further validated by transcriptome analysis of paired pre- and post-treatment biopsies, in situ analysis by multiplex IHC and digital pathology, and in vivo study of an immunogenic hepatocellular carcinoma mouse model. Our findings highlight that anti-VEGF therapy might augment antitumor immunity and enhance anti–PD-L1 immunotherapy by targeting VEGF-mediated angiogenesis, Treg proliferation, and myeloid cell inflammation. Furthermore, our study identified candidate biomarkers for predicting response and resistance to anti–PD-L1 and anti-VEGF combination therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-30T02:16:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005504","title":"WGS Taiwanese urothelial cancers","description":null,"abstract":"WGS of 12 taiwanese urothelial cancers (tumor and adjacent normal tissue) as well as WGS of 12 whole-genome amplified immune cells.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005505","title":"WSSS_Helmsley_Pediatric_gut_multiome","description":"Interrogation of pediatric healthy and Crohn’s gut tissue using multiome methods","abstract":"The gastrointestinal (GI) tract is the biggest interface of our body, a window to our physiology, and is the locus of major diseases, collectively affecting millions of individuals. With the advent of new methods in single-cell and multiome sequencing and computational algorithms, it is clear that an unprecedented high-resolution atlas of the gut in health, and how it changes in disease conditions such as Crohn’s, is now within reach. Such an atlas would allow us to determine the specific cell types in which genetic risk variants act, which cells are affected in disease, which cell programs are changed, which cell–cell communications are disrupted within specific anatomical structures, and even what the effect of therapeutic treatment is and what causes resistance to common therapies. In this study we will sample pediatric GI and process primary single cells and matching cultured organoids using combined single cell ATAC and RNA sequencing of healthy and Crohn’s children.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005506","title":"Single Cell Transcriptomics of peripheral immune cells pre- and post-Immune Checkpoint Blockade","description":null,"abstract":"Raw sequencing data for magnetically-sorted CD8+ T cells and monocytes from the peripheral blood of eight individuals receiving immune checkpoint blockade (either combination ipilimumab/nivolumab, n=4; or single-agent pembrolizumab, n=4) for the treatment of metastatic melanoma. Samples were taken immediately before the first treatment and 21 days post-treatment. Cells were selected based on positivity for CD8 or CD14 and sorted into single cells using the Chromium (10X Genomics) droplet-based system. Gene expression and V(D)J libraries were  prepared in accordance with published protocols before sequencing Illumina HiSeq4000. Analysis of CD8 T cell gene expression and V(D)J features can be found in the associated publication (DOI https://doi.org/10.1101/2020.11.15.383786).","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005507","title":"Single Cell Transcriptomics of peripheral immune cells pre- and post-Immune Checkpoint Blockade","description":null,"abstract":"Raw sequencing data for magnetically-sorted CD8+ T cells and monocytes from the peripheral blood of eight individuals receiving immune checkpoint blockade (either combination ipilimumab/nivolumab, n=4; or single-agent pembrolizumab, n=4) for the treatment of metastatic melanoma. Samples were taken immediately before the first treatment and 21 days post-treatment. Cells were selected based on positivity for CD8 or CD14 and sorted into single cells using the Chromium (10X Genomics) droplet-based system. Gene expression and V(D)J libraries were  prepared in accordance with published protocols before sequencing Illumina HiSeq4000. Analysis of CD8 T cell gene expression and V(D)J features can be found in the associated publication (DOI https://doi.org/10.1101/2020.11.15.383786).","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-30T10:49:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005508","title":"Role of cohesin/CTCF in human monocyte differentiation","description":"Here we study genome architecture in a postmitotic differentiation setting, the differentiation of human blood monocytes (MO). We profiled and compared epigenetic, transcriptome and 3D conformation landscapes during MO differentiation (either into dendritic cells or macrophages) across the genome, with and without siRNA-mediated depletion of RD21 or CTCF, and detected numerous architectural changes, ranging from higher level compartments","abstract":"Here we study genome architecture in a postmitotic differentiation setting, the differentiation of human blood monocytes (MO). We profiled and compared epigenetic, transcriptome and 3D conformation landscapes during MO differentiation (either into dendritic cells or macrophages) across the genome, with and without siRNA-mediated depletion of RD21 or CTCF, and detected numerous architectural changes, ranging from higher level compartments","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-30T14:02:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005509","title":"A Single-cell Atlas of Progressive TKI Resistance in Chronic Myeloid Leukemia","description":"High-dimensional scRNA seq and CyTOF were used to identify features predictive  of treatment outcome at diagnosis. An optimal TKI response was characterised by erythroid lineage skewing of the CD34+ HSPC compartment. While TKI-resistant CP was reminiscent of a BC-like state, where HSPCs were enriched for inflammation, stemness and quiescence. We designed a machine-learning approach which assessed the prognostic potential of all 32 sub-populations of our scRNA seq dataset. LSCs and NK populations harboured the highest prognostic power at diagnosis. Within the LSCs, erythroid lineage priming and MYC activation were features of an optimal and poor TKI responses, respectively. With the NK cell compartment, apart from a higher abundance of NK cells in TKI optimal responders, a memory-like HLA-DR+ adaptive NK  and KLRC1+ NK populations were hallmarks of an optimal and poor TKI responses, respectively.  Mechanistically, both cell intrinsic and extrinsic mechanisms contributed towards the higher sensitivity of EPs to TKI therapy. In summary, our high-dimensional single-cell atlas of TKI resistance highlights pivotal transcriptional features associated with TKI-resistance disease, some of which have the potential to be exploited as biomarkers.","abstract":"High-dimensional scRNA seq and CyTOF were used to identify features predictive  of treatment outcome at diagnosis. An optimal TKI response was characterised by erythroid lineage skewing of the CD34+ HSPC compartment. While TKI-resistant CP was reminiscent of a BC-like state, where HSPCs were enriched for inflammation, stemness and quiescence. We designed a machine-learning approach which assessed the prognostic potential of all 32 sub-populations of our scRNA seq dataset. LSCs and NK populations harboured the highest prognostic power at diagnosis. Within the LSCs, erythroid lineage priming and MYC activation were features of an optimal and poor TKI responses, respectively. With the NK cell compartment, apart from a higher abundance of NK cells in TKI optimal responders, a memory-like HLA-DR+ adaptive NK  and KLRC1+ NK populations were hallmarks of an optimal and poor TKI responses, respectively.  Mechanistically, both cell intrinsic and extrinsic mechanisms contributed towards the higher sensitivity of EPs to TKI therapy. In summary, our high-dimensional single-cell atlas of TKI resistance highlights pivotal transcriptional features associated with TKI-resistance disease, some of which have the potential to be exploited as biomarkers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-30T16:05:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005510","title":"Integrated genomic analysis of tumor thrombus","description":null,"abstract":"We prospectively enrolled 83 patients with a renal mass and TT scheduled to undergo surgical resection.  To accurately integrate genomic and transcriptomic findings and enable histological co-registration, simultaneous isolation of DNA and RNA was performed from individual samples characterized histologically through immediately flanking sections","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005511","title":"Integrated Exome-seq analysis of tumor thrombus","description":"We prospectively enrolled 83 patients with a renal mass and TT scheduled to undergo surgical resection.  To accurately integrate genomic and transcriptomic findings and enable histological co-registration, simultaneous isolation of DNA and RNA was performed from individual samples characterized histologically through immediately flanking sections","abstract":"We prospectively enrolled 83 patients with a renal mass and TT scheduled to undergo surgical resection.  To accurately integrate genomic and transcriptomic findings and enable histological co-registration, simultaneous isolation of DNA and RNA was performed from individual samples characterized histologically through immediately flanking sections","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-30T20:03:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005512","title":"Integrated RNA-seq analysis of tumor thrombus","description":"We prospectively enrolled 83 patients with a renal mass and TT scheduled to undergo surgical resection.  To accurately integrate genomic and transcriptomic findings and enable histological co-registration, simultaneous isolation of DNA and RNA was performed from individual samples characterized histologically through immediately flanking sections","abstract":"We prospectively enrolled 83 patients with a renal mass and TT scheduled to undergo surgical resection.  To accurately integrate genomic and transcriptomic findings and enable histological co-registration, simultaneous isolation of DNA and RNA was performed from individual samples characterized histologically through immediately flanking sections","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-07-30T20:04:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005513","title":"Cancer and germline exomes, and cancer RNA-seq consisiting of FASTQ paired-end reads from melanoma, lung and colon cancer samples","description":"Discovery of patient-specific tumor antigens usually requires in vitro-expanded autologous tumor infiltrating lymphocytes (TILs), among which tumor antigen-specific T cells are however often rare, thus limiting sensitivity. We designed in vitro culture conditions to improve the identification of rare tumor antigen-specific CD8 TILs. This innovative yet accessible pipeline allows highly-sensitive identification of tumor antigens and cognate T cell receptors (TCRs), greatly improving the selection of candidates for personalized cancer vaccines and TCR-based cellular immunotherapies.","abstract":"Discovery of patient-specific tumor antigens usually requires in vitro-expanded autologous tumor infiltrating lymphocytes (TILs), among which tumor antigen-specific T cells are however often rare, thus limiting sensitivity. We designed in vitro culture conditions to improve the identification of rare tumor antigen-specific CD8 TILs. This innovative yet accessible pipeline allows highly-sensitive identification of tumor antigens and cognate T cell receptors (TCRs), greatly improving the selection of candidates for personalized cancer vaccines and TCR-based cellular immunotherapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-02T14:03:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005514","title":"Methylation clocks - individual colon, small intestine and endometrial crypts","description":null,"abstract":"We developed DNA methylation clocks where ongoing (de)methylation causes the clock to ‘tick-tock’ back-and-forth between methylated and unmethylated states. We identified tick-tock CpG sites using standard methylation arrays and developed a mathematical modelling framework to quantitatively measure human adult stem cell dynamics from these data. Small intestinal crypts were inferred to contain slightly more stem cells than colon (6.5 ± 1.0 vs 5.8 ± 1.7 stem cells/crypt) with slower stem cell replacement in small intestine (0.79 ± 0.5 vs 1.1 ± 0.8 replacements/stem cell/year). Germline APC mutation increased the number of replacements per crypt (13.0 ± 2.4 replacements/crypt/year vs 6.9 ± 4.6 for healthy colon).","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-03T13:58:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005515","title":"Long cell-free DNA molecules in maternal plasma","description":"We revealed a large population of long cell-free DNA molecules (up to 23,635 bp in length) in maternal plasma and developed an approach which leveraged the abundance of CpG sites on long molecules to deduce the tissue of origin of individual plasma DNA molecules based on single-molecule methylation analysis. We illustrated how such an approach may be utilized to achieve noninvasive prenatal testing of monogenic diseases. We also revealed a reduction in amounts of such long cell-free DNA molecules and a different end motif profile in maternal plasma DNA from pregnancies with preeclampsia.","abstract":"We revealed a large population of long cell-free DNA molecules (up to 23,635 bp in length) in maternal plasma and developed an approach which leveraged the abundance of CpG sites on long molecules to deduce the tissue of origin of individual plasma DNA molecules based on single-molecule methylation analysis. We illustrated how such an approach may be utilized to achieve noninvasive prenatal testing of monogenic diseases. We also revealed a reduction in amounts of such long cell-free DNA molecules and a different end motif profile in maternal plasma DNA from pregnancies with preeclampsia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-03T14:41:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005516","title":"A renal cell carcinoma tumorgraft platform to advance precision medicine","description":null,"abstract":"Renal cell carcinoma (RCC) encompasses a heterogenous group of diseases, creating challenges for drug development. Preclinical models which are both translatable and representative of disease heterogeneity are needed. Patient-derived xenograft (PDX) or tumorgraft (TG) models recapitulate the biology and treatment responsiveness of RCC. Through the orthotopic implantation into NOD/SCID mice of tumor samples from &amp;gt;900 ethnically-diverse patients at UT Southwestern Medical Center and the affiliated county hospital, we have generated a resource comprising 172 independently-derived stably-engrafted TG lines from 148 patients. The lines have been characterized histologically and genomically (whole exome sequencing [n = 97] and RNA sequencing [n =102]). They represent a variety of histological and on\n cogenotypes including representative TCGA clades further validated through orthogonal metabolomic analyses in a subset. We illustrate how this platform has enabled a deeper understanding of the biology and molecular genetics of RCC, the development of both tissue- and imaging-based biomarkers, as well as advances in drug development. This resource expands the diversity of models available to the scientific community to advance precision diagnosis and therapy in RCC.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-03T17:25:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005517","title":"Differential expression profile of gluten-specific T cells identified by single-cell RNA-seq","description":"Gluten-specific CD4+ T cells drive the pathogenesis of celiac disease and circulating gluten-specific T cells can be identified by staining with HLA-DQ:gluten tetramers. In this first single-cell RNA-seq study of tetramer-sorted T cells from untreated celiac disease patients blood, we found that gluten-specific T cells showed distinct transcriptomic profiles consistent with activated effector memory T cells that shared features with Th1 and follicular helper T cells. Compared to non-specific cells, gluten-specific T cells showed differential expression of several genes involved in T-cell receptor signaling, translational processes, apoptosis, fatty acid transport, and redox potentials. Many of the gluten-specific T cells studied shared T-cell receptor with each other, indicating that circulating gluten-specific T cells belong to a limited number of clones. Moreover, the transcriptional profiles of cells that shared the same clonal origin were transcriptionally more similar compared with between clonally unrelated gluten-specific cells.","abstract":"Gluten-specific CD4+ T cells drive the pathogenesis of celiac disease and circulating gluten-specific T cells can be identified by staining with HLA-DQ:gluten tetramers. In this first single-cell RNA-seq study of tetramer-sorted T cells from untreated celiac disease patients blood, we found that gluten-specific T cells showed distinct transcriptomic profiles consistent with activated effector memory T cells that shared features with Th1 and follicular helper T cells. Compared to non-specific cells, gluten-specific T cells showed differential expression of several genes involved in T-cell receptor signaling, translational processes, apoptosis, fatty acid transport, and redox potentials. Many of the gluten-specific T cells studied shared T-cell receptor with each other, indicating that circulating gluten-specific T cells belong to a limited number of clones. Moreover, the transcriptional profiles of cells that shared the same clonal origin were transcriptionally more similar compared with between clonally unrelated gluten-specific cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-04T11:01:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005518","title":"PPIL4 is essential for brain angiogenesis and implicated in intracranial aneurysm in humans","description":"Rupture of intracranial aneurysms (IAs) leads to subarachnoid hemorrhage (SAH), a sudden-onset disease often causing severe disability or death. Using whole exome sequencing, we identified significant enrichment of rare, deleterious mutations in PPIL4 in both index and familial IA cases. Ppil4 depletion causes intracerebral hemorrhage, defects in cerebrovascular morphology, and impaired Wnt signaling in vivo. Wild type, but not IA-mutant PPIL4, potentiates Wnt signaling by binding JMJD6, a known angiogenesis regulator and Wnt activator. These findings identify a novel PPIL4-dependent Wnt signaling mechanism involved in brain-specific angiogenesis and maintenance of cerebrovascular integrity, and implicate PPIL4 gene variation in the pathogenesis of human IA.","abstract":"Rupture of intracranial aneurysms (IAs) leads to subarachnoid hemorrhage (SAH), a sudden-onset disease often causing severe disability or death. Using whole exome sequencing, we identified significant enrichment of rare, deleterious mutations in PPIL4 in both index and familial IA cases. Ppil4 depletion causes intracerebral hemorrhage, defects in cerebrovascular morphology, and impaired Wnt signaling in vivo. Wild type, but not IA-mutant PPIL4, potentiates Wnt signaling by binding JMJD6, a known angiogenesis regulator and Wnt activator. These findings identify a novel PPIL4-dependent Wnt signaling mechanism involved in brain-specific angiogenesis and maintenance of cerebrovascular integrity, and implicate PPIL4 gene variation in the pathogenesis of human IA.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-04T18:09:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005519","title":"Prognostic effects of serum insulin like growth factor-1 scores in patients with unresectable hepatocellular carcinoma   treated with atezolizumab plus bevacizumab or sorafenib","description":null,"abstract":"Child-Turcotte-Pugh class A (CTP-A) in unresectable hepatocellular carcinoma (HCC) is the standard criterion for active therapy and clinical trial enrollment. Our hypothesis was that insulin-like growth factor-1 (IGF-1)-based scores are more prognostic than CTP classification. This study aimed to evaluate the potential prognostic and predictive effects of IGF-1 and IGF-CTP scores in the phase III IMbrave150 study (NCT03434379).In this exploratory analysis, patients’ baseline serum IGF-1 levels were centrally analyzed. Patients’ IGF-1 scores (1, 2, or 3) and IGF-CTP scores (A, B, or C) were pre-specified based on previously defined cutoffs. The prognostic and predictive values of baseline IGF-1 and IGF-CTP scores for overall survival (OS) and progression-free survival (PFS) were assessed in and between the two treatment arms. The interaction between these scores and OS and PFS was assessed using univariate and multivariate analyses.Of the 501 patients enrolled in the trial, 371 (74%) had evaluable baseline serum IGF-1 levels. Baseline IGF-CTP score (A vs B/C) showed prognostic significance for OS in both the atezolizumab-bevacizumab (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.20 to 0.56; P &lt; .001) and sorafenib (HR, 0.32; 95% CI, 0.16 to 0.65; P = .002) arms. Baseline IGF-1 score (1 vs 2/3) also showed prognostic significance for OS in both the atezolizumab-bevacizumab (HR, 0.33; 95% confidence interval [CI], 0.20 to 0.55; P &lt; .001) and sorafenib (HR, 0.48; 95% CI, 0.26 to 0.89; P = .02) arms. No significant predictive effects were observed for either IGF-CTP score or IGF-1 score between the two treatment arms. In conclusion, baseline IGF-CTP score and IGF-1 score are independent prognostic factors for patients with unresectable HCC treated with atezolizumab-bevacizumab or sorafenib. These novel scores may provide improved patient stratification and outcome prediction in future HCC clinical trials.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005520","title":"Immune profiling reveals enrichment of distinct immune signatures in high-risk oral potentially malignant disorders","description":"Oral epithelial dysplasia (OED) associates with an increased risk of oral squamous cell carcinoma (OSCC). Changes in the immune landscape of OED that accompany transformation remain understudied. We evaluated gene co-expression in benign lesions (fibroepithelial polyps; FEP), high-risk OED (mod-sev OED) and early stage OSCC.  We demonstrate that transcripts indicating immune responses are enriched in high-risk OED. In particular, immune signatures representing high lymphocyte infiltration and cytotoxic responses are prominent, indicating active immunosurveillance. Expression of immune checkpoint molecules was enriched in high-risk OED and further increased in early stage OSCC. Seventy percent of high-risk OED displayed a T cell-inflamed phenotype histology suggesting that they might be responsive to anti-PD-1 immunoprevention. Other immunoprevention strategies are required for the 30% of high-risk OED are not immune-enriched. Overall, our data point the way for new approaches to non-surgical management of OED.","abstract":"Oral epithelial dysplasia (OED) associates with an increased risk of oral squamous cell carcinoma (OSCC). Changes in the immune landscape of OED that accompany transformation remain understudied. We evaluated gene co-expression in benign lesions (fibroepithelial polyps; FEP), high-risk OED (mod-sev OED) and early stage OSCC.  We demonstrate that transcripts indicating immune responses are enriched in high-risk OED. In particular, immune signatures representing high lymphocyte infiltration and cytotoxic responses are prominent, indicating active immunosurveillance. Expression of immune checkpoint molecules was enriched in high-risk OED and further increased in early stage OSCC. Seventy percent of high-risk OED displayed a T cell-inflamed phenotype histology suggesting that they might be responsive to anti-PD-1 immunoprevention. Other immunoprevention strategies are required for the 30% of high-risk OED are not immune-enriched. Overall, our data point the way for new approaches to non-surgical management of OED.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-05T03:03:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005521","title":"Panbody_nanoseq","description":"Different cell types within the human body are subject to different endogenous and exogenous exposures which may result in distinct patterns of mutagenesis. In non-clonal tissues, it is difficult to assess these mutational patterns, including the rate at which they occur. This study will examine the mutational rates and signatures operating across a wide range of normal tissues using the nanoseq technology to reliably call variants, irrespective of their clonal composition. Each cell type will be enriched for using laser capture microdissection. \n\nThis will serve as a reference against which future work on benign and malignant disease entities can be compared.","abstract":"Different cell types within the human body are subject to different endogenous and exogenous exposures which may result in distinct patterns of mutagenesis. In non-clonal tissues, it is difficult to assess these mutational patterns, including the rate at which they occur. This study will examine the mutational rates and signatures operating across a wide range of normal tissues using the nanoseq technology to reliably call variants, irrespective of their clonal composition. Each cell type will be enriched for using laser capture microdissection.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-05T11:35:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005522","title":"The cell free DNA methylome of primary and metastatic prostate tumors","description":null,"abstract":"Metastatic prostate cancer remains a major clinical challenge. Liquid biopsy is emerging as a promising tool in disease management and provides valuable opportunities to gain insights into the underlying biology. Here, we used the highly sensitive, methylated DNA immunoprecipitation coupled to next generation sequencing (MeDIP) technology, to interrogate the cell-free DNA methylomes across localized and metastatic prostate cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-05T19:20:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005523","title":"Pearl study","description":null,"abstract":"Biomarkers to identify patients without benefit from adding everolimus to endocrine treatment in metastatic breast cancer (MBC) are needed. \nWe report the results of the Pearl trial conducted in five Belgian centers assessing 18F-FDG-PET/CT non-response (n=45) and ctDNA detection (n=46) after 14 days of exemestane-everolimus (EXE-EVE) to identify MBC patients who will not benefit. \nMetabolic non-response rate was 66.6%. Median PFS in non-responding patients (using as cut-off 25% for SUVmax decrease) was 3.1 months compared to 6.0 months in those showing response (HR: 0.77, 95% CI: 0.40-1.50, p=0.44). Difference was significant when using a “post-hoc” cut-off of 15% (PFS 2.2 months vs 6.4 months). ctDNA detection at D14 was associated with PFS: 2.1 months vs 5.0 months (HR-2.5, 95% CI: 1.3-5.0, p=0.012). \nDetection of ctDNA and/or the absence of 18F-FDG-PET/CT response after 14 days of EXE-EVE identifies patients with a low probability of benefiting from treatment. Independent validation is needed.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-06T11:55:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005524","title":"Dynamic N6-methyladenosine Epitranscriptomic Landscape in Lung Adenocarcinoma","description":"Systematically evaluate the global effect of dysregulated m6A regulators on the m6A epitranscriptome in patient tumors, and identify prognostic m6A markers by linking with patients' clinicopathological and outcome information.","abstract":"Systematically evaluate the global effect of dysregulated m6A regulators on the m6A epitranscriptome in patient tumors, and identify prognostic m6A markers by linking with patients' clinicopathological and outcome information.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-06T16:51:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005525","title":"Alterations in the gut microbiome in inflammatory arthritis implicate key taxa and metabolic pathways across arthritis phenotypes","description":"The gut microbiome has been implicated in several inflammatory conditions, but large-scale metagenomic evaluations have not yet traced the routes by which immunity in the gut affects systemic inflammatory diseases, such as inflammatory arthritis. To characterize the community structure and associated functional processes driving gut microbial involvement in arthritis, we investigated a total of 440 stool shotgun metagenomes comprising 275 adults diagnosed with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis, along with 165 healthy control individuals and individuals with joint pain without an underlying inflammatory cause.","abstract":"The gut microbiome has been implicated in several inflammatory conditions, but large-scale metagenomic evaluations have not yet traced the routes by which immunity in the gut affects systemic inflammatory diseases, such as inflammatory arthritis. To characterize the community structure and associated functional processes driving gut microbial involvement in arthritis, we investigated a total of 440 stool shotgun metagenomes comprising 275 adults diagnosed with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis, along with 165 healthy control individuals and individuals with joint pain without an underlying inflammatory cause.","study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-08T16:08:01.330207+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005526","title":"APOBEC mutagenesis in EGFR mutant TKI resistance NSCLCs","description":null,"abstract":"Receptor tyrosine kinase (RTK)-activated lung cancers are characterized by alterations in oncogenic drivers that induce kinase activation with resultant tyrosine kinase inhibitor (TKI) resistance through both on-target and off-target mechanisms. \nFocusing on a subgroup of 93 EGFR-mutant lung cancers with paired osimertinib-naïve and osimertinib-resistant tumor samples, we find a significant enrichment of kataegis, chromothripsis and APOBEC mutagenesis among the cancers treated with targeted therapy.  \nAPOBEC mutagenesis and structural rearrangements are pervasive mechanisms by which RTK-driven lung cancers may evolve and develop drug resistance.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-06T22:19:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005527","title":"Defining the origins of aggressive medulloblastomas through scRNA-seq of human fetal cerebella","description":null,"abstract":"We used single-cell transcriptomics and single-cell ATAC to study &gt;350,000 cells from the developing human embryo cerebellum and pediatric medulloblastoma, and highlight the distinct human fetal cerebellar development program and reveal the tumoral alteration based on the gene expression and chromatin status.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005528","title":"CRISPR_single_cell_activation","description":"Single cell CRISPR activitaion analysis with 96 genes with the aim to build a quantative CRISPR activation model. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Single cell CRISPR activitaion analysis with 96 genes with the aim to build a quantative CRISPR activation model. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-09T08:25:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005529","title":"Multi-omics integration reveals only minor long-term molecular and functional sequelae in immune cells of individuals recovered from COVID-19","description":"The majority of COVID-19 patients experience mild to moderate disease course and recover within a few weeks. An increasing number of studies characterized the long-term changes in the specific anti-SARS-CoV-2 immune responses, but how COVID-19 shapes the innate and heterologous adaptive immune system after recovery is less well known. To comprehensively investigate the post-SARS-CoV-2 infection sequelae on the immune system, we performed a multi-omics study by integrating single-cell RNA-sequencing, single-cell ATAC-sequencing, genome-wide DNA methylation profiling, and functional validation experiments in convalescent COVID-19 and healthy individuals. We showed that immune responses generally recover without major sequelae after COVID-19. However, subtle differences persist at the transcriptomic level in monocytes, with downregulation of the interferon pathway, while DNA methylation also displays moderate changes in convalescent COVID-19 individuals. However, these differences did not affect the cytokine production capacity of PBMCs upon different bacterial, viral, and fungal stimuli, although baseline release of IL-1RA and IFN?? was higher in convalescent individuals. In conclusion, despite minor differences in epigenetic and transcriptional programs, the immune system of convalescent COVID-19 patients largely recovers to the homeostatic level of healthy individuals.","abstract":"The majority of COVID-19 patients experience mild to moderate disease course and recover within a few weeks. An increasing number of studies characterized the long-term changes in the specific anti-SARS-CoV-2 immune responses, but how COVID-19 shapes the innate and heterologous adaptive immune system after recovery is less well known. To comprehensively investigate the post-SARS-CoV-2 infection sequelae on the immune system, we performed a multi-omics study by integrating single-cell RNA-sequencing, single-cell ATAC-sequencing, genome-wide DNA methylation profiling, and functional validation experiments in convalescent COVID-19 and healthy individuals. We showed that immune responses generally recover without major sequelae after COVID-19. However, subtle differences persist at the transcriptomic level in monocytes, with downregulation of the interferon pathway, while DNA methylation also displays moderate changes in convalescent COVID-19 individuals. However, these differences did not affect the cytokine production capacity of PBMCs upon different bacterial, viral, and fungal stimuli, although baseline release of IL-1RA and IFN?? was higher in convalescent individuals. In conclusion, despite minor differences in epigenetic and transcriptional programs, the immune system of convalescent COVID-19 patients largely recovers to the homeostatic level of healthy individuals.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-09T09:55:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005530","title":"Pathogenic Neurofibromatosis type 1 (NF1) RNA splicing resolved by targeted RNAseq","description":"Neurofibromatosis type 1 (NF1) is caused by loss-of-function variants in the NF1 gene. Approximately 10% of these variants affect RNA splicing and are either missed by conventional DNA diagnostics or are misinterpreted by in silico splicing predictions. Therefore, a targeted RNAseq-based approach was designed to detect pathogenic RNA splicing and associated pathogenic DNA variants. an in-house developed tool (QURNAS) was used to calculate the enrichment score (ERS) for each splicing event. RNA enrichment of NF1 and SPRED1 was done using SPET (NUGEN - NF1 only) and using SureSelect (Agilent - NF1 and SPRED1).","abstract":"Neurofibromatosis type 1 (NF1) is caused by loss-of-function variants in the NF1 gene. Approximately 10% of these variants affect RNA splicing and are either missed by conventional DNA diagnostics or are misinterpreted by in silico splicing predictions. Therefore, a targeted RNAseq-based approach was designed to detect pathogenic RNA splicing and associated pathogenic DNA variants. an in-house developed tool (QURNAS) was used to calculate the enrichment score (ERS) for each splicing event. RNA enrichment of NF1 and SPRED1 was done using SPET (NUGEN - NF1 only) and using SureSelect (Agilent - NF1 and SPRED1).","study_type":"Other","pubmed_ids":[34782607],"external_links":null,"is_released":true,"released_date":"2021-08-09T10:09:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005531","title":"Exploring_the_immunological_mechanisms_contributing_to_symptomatic_and_asymptomatic_visceral_leishmaniasis_in_Ethiopia__a_pilot_study","description":"This study will allow us to plan and design a longitudinal analyses to identify genes and immunological\npathways associated with different stages in the onset and development of asymptomatic infections and\nsymptomatic VL. The WSI contribution will be to perform RNAseq and perform initial analysis of the data to confirm that the samples are of high enough quality and to establish the pattern of gene expression in these samples which will enable statistical design of a more comprehensive study.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Exploring the immunological mechanisms contributing to symptomatic and asymptomatic visceral leishmaniasis in Ethiopia: a pilot study","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005532","title":"PAH sequencing study","description":"The Cohort study of idiopathic and heritable PAH is an observational, prospective and longitudinal study of patients with idiopathic and heritable PAH. Follow-up information is collected as a part of routine clinical care every six months. The study allows recruitment of both incident and prevalent cases. Patients consented to the study agreed to have blood taken for next-generation sequencing and other omics studies.","abstract":"The Cohort study of idiopathic and heritable PAH is an observational, prospective and longitudinal study of patients with idiopathic and heritable PAH. Follow-up information is collected as a part of routine clinical care every six months. The study allows recruitment of both incident and prevalent cases. Patients consented to the study agreed to have blood taken for next-generation sequencing and other omics studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-09T16:32:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005533","title":"SJCRH Patient-derived orthotopic xenografts of pediatric brain tumors","description":"Primary patient pediatric brain tumors from patients treated at SJCRH were implanted and amplified only in the brain of immunocompromised mice without tissue culture steps and referred as patient-derived orthotopic xenografts (Smith et al, Acta Neuropathologica, 2020).","abstract":"Primary patient pediatric brain tumors from patients treated at SJCRH were implanted and amplified only in the brain of immunocompromised mice without tissue culture steps and referred as patient-derived orthotopic xenografts (Smith et al, Acta Neuropathologica, 2020).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-09T17:18:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005534","title":"HSC_colony_many_years_post_allogeneic_bone_marrow_transplant___Bait_set_2","description":"This study looks at human donors and recipients of allogeneic blood &amp; marrow marrow transplantation. Each transplant \"pair\" (donor &amp; recipient) underwent the transplant procedure 10 -30 years prior to sampling - the majority for an underlying diagnosis of leukemia.  We will perform whole-genome sequencing on tens to hundreds of single HSPC (haematopoietic stem and progenitor cell)-derived colonies per individual. We will infer the phylogeny of these cells (those from both donor &amp; recipient within a pair) by analysing the somatically acquired mutations within each cell. The structure of the phylogeny will allow estimates of hitherto unknown parameters such as the number of HSCs that engraft long-term, the dynamics of the engraftment process on the HSC level, and the additional mutation burden acquired through the arduous transplant procedure.\nThis TGS part of the study is used for assessing the contribution of clones to mature blood subsets, and better timing mutations relative to transplantation.","abstract":"We propose the use of whole genome sequencing, along with state-of-the-art phylogenetic methods, to reconstruct the dynamics of stem cell engraftment in patients undergoing allogeneic stem cell transplantation for haematological disease:\n\t\n-\tHow many infused haematopoietic stem cells successfully engraft and contribute to subsequent haematopoiesis in human recipients?\n-\tWhat is the time course and phylogenetic structure of stem cell reconstitution?\n-\tAre the outputs of individual engrafting stem_cells biased towards particular lineages e.g. myeloid vs B/T lymphoid?\n\nWithin our study cohort we anticipate a variety of recipient/ donor characteristics, conditioning regimens (myeloablative or reduced-intensity) and other transplant variables (e.g. transplanted cell dose).  Although this study will not have statistical power to draw definitive conclusions on how these differences affect transplant phylodynamics it will establish proof of principle for this type of analysis and inform hypotheses for future studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-11T12:32:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005535","title":"Pancreatic islets PISA RNA-seq samples","description":"GWAS have identified more than 700 genetic signals associated with type 2 diabetes (T2D). To gain insight into the underlying molecular mechanisms, we created the Translational human pancreatic Islet Genotype tissue-Expression Resource (TIGER), aggregating &gt;500 human islet RNA-seq and genotyping datasets. We imputed genotypes using 4 reference panels and meta-analyzed cohorts to improve coverage of expression quantitative trait loci (eQTL) and developed a method to combine allele-specific expression across samples (cASE). We identified &gt;1 million islet eQTLs (56% novel), of which 53 colocalize with T2D signals (60% novel). Among them, a low-frequency allele that reduces T2D risk by half increases CCND2 expression. We identified 8 novel cASE colocalizations, among which an SLC30A8 T2D associated variant. We make all the data available through the open-access TIGER portal (http://tiger.bsc.es), which represents a comprehensive human islet genomic data resource to elucidate how genetic variation affects islet function and translate this into therapeutic insight and precision medicine for T2D.","abstract":"GWAS have identified more than 700 genetic signals associated with type 2 diabetes (T2D). To gain insight into the underlying molecular mechanisms, we created the Translational human pancreatic Islet Genotype tissue-Expression Resource (TIGER), aggregating &gt;500 human islet RNA-seq and genotyping datasets. We imputed genotypes using 4 reference panels and meta-analyzed cohorts to improve coverage of expression quantitative trait loci (eQTL) and developed a method to combine allele-specific expression across samples (cASE). We identified &gt;1 million islet eQTLs (56% novel), of which 53 colocalize with T2D signals (60% novel). Among them, a low-frequency allele that reduces T2D risk by half increases CCND2 expression. We identified 8 novel cASE colocalizations, among which an SLC30A8 T2D associated variant. We make all the data available through the open-access TIGER portal (http://tiger.bsc.es), which represents a comprehensive human islet genomic data resource to elucidate how genetic variation affects islet function and translate this into therapeutic insight and precision medicine for T2D.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-13T08:30:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005536","title":"Transcriptome Changes in ASD (NRXN1α+/-) iPSC-derived neurons","description":"NRXN1 deletions are identified as one of major rare risk factors for autism spectrum disorder (ASD) and other neurodevelopmental disorders. ASD has 30% co-morbidity with epilepsy and the latter is associated with excessive neuronal firing. NRXN1 encodes hundreds of presynaptic neuro-adhesion proteins categorized as NRXN1α/β/γ. Previous studies on cultured cells show that the short NRXN1β primarily exerts excitation effect, whereas the long NRXN1α which is more commonly deleted in patients involves in both excitation and inhibition. However, patient-derived models are essential for understanding functional consequences of NRXN1α deletions in human neurons\n\nQuantitative RNA sequencing was performed by BGI using 50bp single-end strategy with BGI-SEQ500 sequencing device on iPSC-derived cortical neurons from 6 control lines; (2VC1, 3VCX1, 3VC2, 4C3, 4CX1, NCRM-1) of 4 healthy donors, and 4 NRXN1α+/- lines; (ND1C1, ND2C11, ND2CX1, ND4-1C2) from 3 ASD patients.","abstract":"NRXN1 deletions are identified as one of major rare risk factors for autism spectrum disorder (ASD) and other neurodevelopmental disorders. ASD has 30% co-morbidity with epilepsy and the latter is associated with excessive neuronal firing. NRXN1 encodes hundreds of presynaptic neuro-adhesion proteins categorized as NRXN1α/β/γ. Previous studies on cultured cells show that the short NRXN1β primarily exerts excitation effect, whereas the long NRXN1α which is more commonly deleted in patients involves in both excitation and inhibition. However, patient-derived models are essential for understanding functional consequences of NRXN1α deletions in human neurons\n\nQuantitative RNA sequencing was performed by BGI using 50bp single-end strategy with BGI-SEQ500 sequencing device on iPSC-derived cortical neurons from 6 control lines; (2VC1, 3VCX1, 3VC2, 4C3, 4CX1, NCRM-1) of 4 healthy donors, and 4 NRXN1α+/- lines; (ND1C1, ND2C11, ND2CX1, ND4-1C2) from 3 ASD patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-13T12:05:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005537","title":"Germline variants in patients with rare cancers and their implications for precision cancer medicine: experiences from the Multicenter MASTER Trial by the German Cancer Consortium (HIPO_021)","description":"The era of precision oncology entails an increasing amount of molecular data from tumor sequencing in research and diagnostics. In this setting, germline variant analysis may add clinical benefits for patients and family members. In this study, we evaluated germline variants from genome/exome matched tumor-blood sequencing in 1.485 advanced cancer patients within a prospective observational study carried out by the German Cancer Consortium. Included patients had cancers of rare entities (79.2%) or were under the age of 51 at first diagnosis (76.6%). Ten percent of the patients harbored pathogenic germline variants in 35 tumor predisposition genes with autosomal-dominant inheritance such as BRCA1, BRCA2, TP53, RB1, CHEK2, ATM, PALB2, SDHB etc., while 4.6% of the patients were carriers of pathogenic germline variants in 18 genes with autosomal-recessive inheritance of tumor predisposition. Based on pathogenic germline variants, 14% of the patients received genetic counselling recommendations in the molecular tumor board report. Forty five percent of pathogenic germline variants supported a molecular treatment recommendation, which was implemented for 28 patients. Furthermore, we compared our approach and results to previous studies, broadening the insight into pan cancer germline findings but also revealing differences between studies on various levels, such as cohort demographics, tumor entities, gene nominations, variant detection and variant interpretation. Our data support the importance of germline variant interpretation in precision oncology studies for patients and their families, if applicable. However, guidelines for evaluation and reporting of germline variants in the context of genetic tumor profiling need to be established and further research on the relevance of germline mutations as biomarkers for treatment recommendations is needed.","abstract":"The era of precision oncology entails an increasing amount of molecular data from tumor sequencing in research and diagnostics. In this setting, germline variant analysis may add clinical benefits for patients and family members. In this study, we evaluated germline variants from genome/exome matched tumor-blood sequencing in 1.485 advanced cancer patients within a prospective observational study carried out by the German Cancer Consortium. Included patients had cancers of rare entities (79.2%) or were under the age of 51 at first diagnosis (76.6%). Ten percent of the patients harbored pathogenic germline variants in 35 tumor predisposition genes with autosomal-dominant inheritance such as BRCA1, BRCA2, TP53, RB1, CHEK2, ATM, PALB2, SDHB etc., while 4.6% of the patients were carriers of pathogenic germline variants in 18 genes with autosomal-recessive inheritance of tumor predisposition. Based on pathogenic germline variants, 14% of the patients received genetic counselling recommendations in the molecular tumor board report. Forty five percent of pathogenic germline variants supported a molecular treatment recommendation, which was implemented for 28 patients. Furthermore, we compared our approach and results to previous studies, broadening the insight into pan cancer germline findings but also revealing differences between studies on various levels, such as cohort demographics, tumor entities, gene nominations, variant detection and variant interpretation. Our data support the importance of germline variant interpretation in precision oncology studies for patients and their families, if applicable. However, guidelines for evaluation and reporting of germline variants in the context of genetic tumor profiling need to be established and further research on the relevance of germline mutations as biomarkers for treatment recommendations is needed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-13T13:11:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005538","title":"Single_cell_transcriptional_profiling_of_T_cell_metabolism","description":"T cell activation and proliferation in response of foreign antigen is a cardinal process of the adaptive immune response. These processes require a change in cell metabolism to adapt to the higher energetic requirements and cellular resources.  In this project we aimed to understand the transcriptional changes that accompany perturbations of metabolic pathways as T cells undergo activation and proliferation. We perturbed stimulated CD4+ naive and memory T cells with 19 compounds which target various known metabolic pathways, followed by single cell transcriptional profiling.These resulted in a dataset encompassing 80 conditions (19 compounds + 1 control without drug), in  both naive and memory CD4+ T cells at 2 different time points (16 hours and three days after perturbations).","abstract":"T cell activation and proliferation in response of foreign antigen is a cardinal process of the adaptive immune response. These processes require a change in cell metabolism to adapt to the higher energetic requirements and cellular resources.  In this project we aimed to understand the transcriptional changes that accompany perturbations of metabolic pathways as T cells undergo activation and proliferation. We perturbed stimulated CD4+ naive and memory T cells with 19 compounds which target various known metabolic pathways, followed by single cell transcriptional profiling.These resulted in a dataset encompassing 80 conditions (19 compounds + 1 control without drug), in  both naive and memory CD4+ T cells at 2 different time points (16 hours and three days after perturbations).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005539","title":"Clonal dynamics of normal hepatocyte expansions in homeostatic human livers and their association with the biliary epithelium","description":null,"abstract":"The majority of human liver research is disease-focused such that far less is known of cellular dynamics within morphologically normal human liver. We have leveraged cytochrome c oxidase deficiency as a marker of clonal hepatocyte populations in such tissues. We demonstrate these populations commonly associate with portal tracts and lineage-trace hepatocytes with cholangiocytes, indicating the presence of a bipotential common ancestor at this niche. We also observe rare periportal SOX9+ hepatocytes progenitor candidates in our human tissues. To understand clonal expansion dynamics, we measured methylation diversity and identified mtDNA variants by next-generation sequencing within spatially-defined clonal hepatocyte patches. We coupled our sequencing with mathematical modelling and Bayesian inference to compare spatial patterns of mtDNA variants under assumptions with or without faster expansion from a portal-associated niche. These datasets support the existence of a periportal progenitor niche and indicate that clonal patches slowly expand, perhaps due to acute environmental stimuli, then quiesce. These findings crucially contribute to our limited understanding of hepatocyte dynamics in normal human liver and provide a baseline for further understanding how they may be modulated in diseased liver.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-13T19:32:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005540","title":"Mitochondrial DNA sequencing","description":null,"abstract":"We studied 44 rectal cancer patients enrolled onto a prospective population-based biomarker study, who were planned for curative-intent radiation therapy before definitive surgery, yet at high risk of metastatic progression beyond the pelvic cavity. The patients had full-length mtDNA sequencing of whole blood (WB) and peripheral blood mononuclear cells (PBMC), sampled at the time of diagnosis. Metastatic events were recorded up to 60 months of follow-up after completion of the multimodal treatment.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-15T12:24:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005541","title":"Single-cell RNA-seq data of the tumor microenvironment of lymphocyte-rich Hodgkin lymphoma and other Hodgkin lymphoma subtypes","description":"Lymphocyte-rich classic Hodgkin lymphoma (LR-CHL) is a rare subtype of Hodgkin lymphoma. Recent technical advances have allowed for the characterization of specific crosstalk mechanisms between malignant Hodgkin Reed-Sternberg (HRS) cells and different normal immune cells in the tumor microenvironment (TME) of CHL. However, the TME of LR-CHL has not yet been characterized at single cell resolution. Here, using single cell RNA sequencing, we examined the immune cell profile of 8 cell suspension samples of LR-CHL in comparison to 20 samples of the mixed cellularity (9 cases) and nodular sclerosis (11 cases) subtypes of CHL, as well as 5 reactive lymph node controls.","abstract":"Lymphocyte-rich classic Hodgkin lymphoma (LR-CHL) is a rare subtype of Hodgkin lymphoma. Recent technical advances have allowed for the characterization of specific crosstalk mechanisms between malignant Hodgkin Reed-Sternberg (HRS) cells and different normal immune cells in the tumor microenvironment (TME) of CHL. However, the TME of LR-CHL has not yet been characterized at single cell resolution. Here, using single cell RNA sequencing, we examined the immune cell profile of 8 cell suspension samples of LR-CHL in comparison to 20 samples of the mixed cellularity (9 cases) and nodular sclerosis (11 cases) subtypes of CHL, as well as 5 reactive lymph node controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-16T16:58:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005542","title":"Sequencing_of_perilesional_skin_and_tumour","description":"We wish to assess clone size and frequency immediately adjacent to skin SCC.","abstract":"We wish to assess clone size and frequency immediately adjacent to skin SCC.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005543","title":"Multipolar zygotic divisions are characterized by parental genome segregation errors","description":null,"abstract":"The first mitotic division causes both parental genomes present in the zygote to segregate into two biparental diploid daughter cells. This fundamental tenet was challenged by the observation that blastomeres with different genome ploidy and distinct parental genotypes can coexist within individual embryos. We hypothesized that whole parental genomes can segregate into distinct blastomere lines during the multipolar division of the zygote, a phenomenon referred to as “heterogoneic” cell division. Here, we provide evidence of genome-wide segregation errors in two human blastocysts and further pinpoint its origin in a bovine model by mapping the genomic landscape of 82 blastomeres from 25 embryos that underwent multipolar division at the zygote stage using genome-wide SNP arrays and sequencing. In most embryos, the coexistence of androgenetic and diploid or polyploid blastomeres with or without anuclear blastomeres, androgenetic and anuclear blastomeres, and androgenetic and gynogenetic blastomeres within the same embryo provided proof that multipolar zygotic division coincides with heterogoneic segregation of the parental genome. By mapping the segregational origin of the genomic content, we deduced distinct segregation mechanisms underlying heterogoneic cell division including segregation by a tripolar spindle, the pronuclear extrusion of a paternal genome and, the operation of an ectopic paternal or private parental spindles. Polyspermic embryos expel excessive paternal genomes resulting in an androgenetic or polyploid blastomere Confirming the results in human blastocysts we found genome-wide segregation errors  to persist in bovine blastocysts.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-17T15:14:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005544","title":"Investigation of the keratinocytic gene expression pattern in Hidradenitis suppurativa","description":"The underlying pathogenetic factors generating the innate immune signal necessary for T cell activation, initiation and chronification of Hidradenitis suppurativa (HS, also known as Acne inversa) are still poorly understood. Emerging evidence suggests that defective keratinocyte function critically contributes to HS disease development and progression. To elucidate the role of keratinocytes in HS lesion formation, we compared the transcriptomes of isolated lesional and perilesional HS epidermis by RNA sequencing.","abstract":"The underlying pathogenetic factors generating the innate immune signal necessary for T cell activation, initiation and chronification of Hidradenitis suppurativa (HS, also known as Acne inversa) are still poorly understood. Emerging evidence suggests that defective keratinocyte function critically contributes to HS disease development and progression. To elucidate the role of keratinocytes in HS lesion formation, we compared the transcriptomes of isolated lesional and perilesional HS epidermis by RNA sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-18T08:16:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005545","title":"Longitudinal Single Cell Atlas of COVID-19 Identifies an Early, Transient Prognostic Signature","description":null,"abstract":"Although the majority of COVID-19 patients are asymptomatic or mildly symptomatic at diagnosis, some will subsequently progress to pneumonia, oxygen desaturation and other symptoms requiring active clinical management. However, molecular markers that identify high-risk patients early in the disease course (Days 1-8 from symptom onset) are scarce, due to the paucity of relevant longitudinal studies. We performed longitudinal single cell RNA-seq on 286 peripheral blood samples from 108 COVID-19 patients, 73 of which had at least one early sample. By examining discrete cell subtypes as well as continuous single cell states, we identified upregulation of type I IFN response genes as the predominant cellular prognostic signature of future disease severity. Type I IFN response was dynamic and complex, spiking early in progressors and then regressing to the cohort mean at the very next sampling, with the cohort mean itself receding to asymptomatic levels by Day 14 regardless of severity. Moreover, in severe and critical cases, IFN response was impaired during Days 5-8, partially due to upregulation of SOCS3 and other negative regulators. We have identified an early prognostic signature for predicting COVID-19 severity as well as potential mechanisms underlying the dysfunctional host immune response in severe disease.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-18T14:06:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005546","title":"Minor intron splicing efficiency increases with the development of lethal prostate cancer","description":null,"abstract":"We sought to determine the effect of a minor spliceosome inhibition by U6atac snRNA depletion in prostate cancer. We performed siRNA-mediated knock-down (96h) of the minor spliceosome snRNA U6atac  in androgen-sensitive LNCaP cells,  androgen-insensitive C4-2 and 22Rv1 cells and in patient derived neuroendocrine organoids  (PM154). We compared global transcriptional alterations and lineage dependency using RNA-seq and scRNAseq.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-19T08:11:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005547","title":"WSSS_Skin","description":"WSSS Deep dive of healthy human adult skin\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"WSSS Deep dive of healthy human adult skin\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005548","title":"HCA_Gonads_Foetal_Vento_DNA","description":"Cell atlas of mouse gonads","abstract":"Sequencing of mouse gonads using 10x single cell techniques to support on-going HCA reproductive research.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005549","title":"Expression-Based Subtypes Define Pathologic Response to Neoadjuvant Immune-Checkpoint Inhibitors in Muscle-Invasive Bladder Cancer","description":"Checkpoint immunotherapy (CPI) has increased survival for some patients with advanced stage bladder cancer (BCa). However, most patients do not respond. Here, we characterized the tumor and immune microenvironment in pre- and post-treatment tumors from the PURE01 neoadjuvant pembrolizumab immunotherapy trial, using a consolidative approach that combined transcriptional and genetic profiling with digital spatial profiling.","abstract":"Checkpoint immunotherapy (CPI) has increased survival for some patients with advanced stage bladder cancer (BCa). However, most patients do not respond. Here, we characterized the tumor and immune microenvironment in pre- and post-treatment tumors from the PURE01 neoadjuvant pembrolizumab immunotherapy trial, using a consolidative approach that combined transcriptional and genetic profiling with digital spatial profiling.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-19T19:44:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005550","title":"Genomic characterization of retinoblastoma (targeted sequencing)","description":"Retinoblastoma is the most frequent intraocular malignancy in children, originating from a maturing cone precursor in the developing retina. Little is known on the molecular basis underlying the biological and clinical behavior of this cancer. Here, using multi-omics data, we demonstrate the existence of two retinoblastoma subtypes. Subtype 1, of earlier onset, includes most of the heritable forms. It harbors few genetic alterations other than the initiating RB1 inactivation and corresponds to differentiated tumors expressing mature cone markers. By contrast, subtype 2 tumors harbor frequent recurrent genetic alterations including MYCN-amplification. They express markers of less differentiated cone together with neuronal/ganglion cell markers with marked inter- and intra-tumor heterogeneity. The cone dedifferentiation in subtype 2 is associated with stemness features including low immune and interferon response, E2F and MYC/MYCN activation and a higher propensity for metastasis. The recognition of these two subtypes, one maintaining a cone-differentiated state, and the other, more aggressive, associated with cone dedifferentiation and expression of neuronal markers, opens up important biological and clinical perspectives for retinoblastomas.\nIn this study, we performed targeted sequencing of the exonic regions of RB1, BCOR and ARID1A on 37 samples from the series of 102 retinoblastomas. Among them, 23 samples were not subjected to whole-exome sequencing, and 14 samples have the whole-exome sequencing data (deposited in EGAS00001005248).","abstract":"Retinoblastoma is the most frequent intraocular malignancy in children, originating from a maturing cone precursor in the developing retina. Little is known on the molecular basis underlying the biological and clinical behavior of this cancer. Here, using multi-omics data, we demonstrate the existence of two retinoblastoma subtypes. Subtype 1, of earlier onset, includes most of the heritable forms. It harbors few genetic alterations other than the initiating RB1 inactivation and corresponds to differentiated tumors expressing mature cone markers. By contrast, subtype 2 tumors harbor frequent recurrent genetic alterations including MYCN-amplification. They express markers of less differentiated cone together with neuronal/ganglion cell markers with marked inter- and intra-tumor heterogeneity. The cone dedifferentiation in subtype 2 is associated with stemness features including low immune and interferon response, E2F and MYC/MYCN activation and a higher propensity for metastasis. The recognition of these two subtypes, one maintaining a cone-differentiated state, and the other, more aggressive, associated with cone dedifferentiation and expression of neuronal markers, opens up important biological and clinical perspectives for retinoblastomas.\nIn this study, we performed targeted sequencing of the exonic regions of RB1, BCOR and ARID1A on 37 samples from the series of 102 retinoblastomas. Among them, 23 samples were not subjected to whole-exome sequencing, and 14 samples have the whole-exome sequencing data (deposited in EGAS00001005248).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-19T19:52:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005551","title":"Comprehensive molecular analysis of inflammatory myofibroblastic tumors reveals diverse genomic landscape and potential predictive markers for crizotinib response","description":null,"abstract":"Abstract\nPurpose:\nThe clinical phase 2 trial EORTC 90101 “CREATE” showed high anti-tumor activity of crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK)/ROS1, in patients with advanced inflammatory myofibroblastic tumor (IMFT). Recent findings suggested also that molecular targets beyond ALK/ROS1 might contribute to the sensitivity to this kinase inhibitor. We therefore performed an in-depth molecular characterization of archival IMFT tissue, collected from patients enrolled in this trial, with the aim to identify other molecular alterations which could play a role in the response to crizotinib.\n\nExperimental Design:\nTwenty-four archival IMFT samples were used for histopathological assessment and DNA/RNA evaluation to identify gene fusions, copy number alterations (CNAs) and mutations in the tumor tissue. Results were correlated with clinical parameters to assess a potential association between molecular findings and clinical outcome. \n\nResults:\nWe found 12 ALK fusions with 11 different partners in ALK-positive IMFT cases by Archer analysis while we did not identify any ROS1-rearranged tumor. One ALK-negative patient responding to crizotinib was found to have an ETV6-NTRK fusion in the tumor specimen. The CNA profile and mutational landscape of IMFT revealed extensive molecular heterogeneity. Loss of chromosome 19 (25% of cases) and PIK3CA mutations (9% of cases) were associated with shorter progression-free survival in patients receiving crizotinib. \n\nConclusions:\nWe identified multiple genetic alterations in archival IMFT material and provide further insight in the molecular profile of this ultra-rare, heterogeneous malignancy, which may potentially translate into novel treatment approaches for this orphan disease.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005552","title":"Mutational_burden_in_oesophagus_following_chemotherapy_and_radiotherapy_treatment","description":"We wish to assess the changes in signature and mutational burden in patients who have undergone either chemotherapy or chemotherapy + radiotherapy.  Using duplex sequencing will assess the mutational landscape in oesophageal epithelia in patients who have undergone these treatment regimes.","abstract":"We wish to assess the changes in signature and mutational burden in patients who have undergone either chemotherapy or chemotherapy + radiotherapy.  Using duplex sequencing will assess the mutational landscape in oesophageal epithelia in patients who have undergone these treatment regimes.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-20T11:34:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005553","title":"Pediatric study using genome sequencing","description":"This study used whole genome sequencing to assess genome variants from DNA from pediatric individuals seen in genetics clinic who were thought to have genetic conditions.","abstract":"This study used whole genome sequencing to assess genome variants from DNA from pediatric individuals seen in genetics clinic who were thought to have genetic conditions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-20T18:46:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005554","title":"DLBCL NGS Genomic Datasets of non-China cohort from Phoenix Clinical Trial","description":"Study biopsies (n=773; 189 cases as China cohort and 584 cases as non-China cohort) underwent whole exome sequencing or targeted gene panel DNA sequencing and RNA sequencing, allowing the identification of somatic mutations. Tumors were assigned to DLBCL genetic subtypes as the MCD (n=110), BN2 (n=47) or N1 (n=28) using the LymphGen algorithm based on their somatically mutated genes. In younger patients (age≤60), ibrutinib plus R-CHOP was associated with a 100% event free survival (EFS) at 3-years in the MCD and N1 groups, whereas R-CHOP alone was associated with a 3-year EFS of 42.9% (p=0.01) and 50% (p=0.016) in the MCD and N1 groups, respectively. This analysis showed a benefit of ibrutinib with R-CHOP chemotherapy in particular genetic subtypes, providing mechanistic support for its survival benefit in younger patients with non-GCB DLBCL. The EGA collects RNA-Seq and NuGene targeted sequencing datasets of 584 cases for non-China cohort.","abstract":"Study biopsies (n=773; 189 cases as China cohort and 584 cases as non-China cohort) underwent whole exome sequencing or targeted gene panel DNA sequencing and RNA sequencing, allowing the identification of somatic mutations. Tumors were assigned to DLBCL genetic subtypes as the MCD (n=110), BN2 (n=47) or N1 (n=28) using the LymphGen algorithm based on their somatically mutated genes. In younger patients (age≤60), ibrutinib plus R-CHOP was associated with a 100% event free survival (EFS) at 3-years in the MCD and N1 groups, whereas R-CHOP alone was associated with a 3-year EFS of 42.9% (p=0.01) and 50% (p=0.016) in the MCD and N1 groups, respectively. This analysis showed a benefit of ibrutinib with R-CHOP chemotherapy in particular genetic subtypes, providing mechanistic support for its survival benefit in younger patients with non-GCB DLBCL. The EGA collects RNA-Seq and NuGene targeted sequencing datasets of 584 cases for non-China cohort.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-22T22:54:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005555","title":"In_situ_clonal_heterogeneity_at_prostate_diagnostic_biopsy_and_outcome_implications","description":"This study aims at reconstructing the cellular heterogeneity of the tumor in multi-needle diagnostic\nprostate biopsy as well as any biopsy containing potentially pre-malignant tissue, to study its implications\nin the clinical history of the disease. The characterization of the relationships between pathological\ndiagnosis (Gleason score) and genomic heterogeneity will be the main focus, with the goal of\nestablishing a connection between observed cell dysplasia and genome aberrations. In parallel, the\nassociation of individual clinical features with clonal heterogeneity at diagnosis will be evaluated as a\nproxy for long-term disease outcome.","abstract":"Prostate cancer (PCa) is the leading malignancy of the male population. In current clinical practice,\ndiagnostic confirmation of PCa is based on image-guided multi-needle biopsy, in order to capture the\nintrinsic biological heterogeneity of tumors and to provide a more accurate prediction of clinical\noutcomes. However, current morphology-based approaches (Gleason score) may not completely\ndescribe the complexity of a malignant gland. Not enough is currently known on the impact of genomic\nheterogeneity in a poorly-differentiated prostate, especially with regards to the development of an\nindolent versus metastatic prostate malignancy (Robinson, et al., 2015).\n\nThe study will include 280 prostatic diagnostic biopsies from a cohort of 20 early metastatic PC patients\nand 20 non-relapsing/non-metastatic patients with indolent malignant disease. All subjects will be\nidentified and treated at the Oncology Expertise Center of the Clinica Luganese Moncucco Hospital\n(Lugano, CH). The included patients will have a clinical follow-up with regular plasma PSA levels for\ndisease characterization, plus complete treatment history. For each patient, 4 or more samples will be\nprepared starting from the FFPE diagnostic material. Specifically, the two biopsies used for assigning the\nGleason score will be sequenced, together with two or more of the local peri-proximal biopsies with a\nhigher level of differentiation. Samples will undergo Whole Exome Sequencing (WES) with an average\ncoverage of 200x at the Wellcome Sanger Institute (WSI, Hinxton, UK). Sequencing data will be analysed\nfor single nucleotide variants (SNVs), copy number variants (CNVs) and structural variants (SVs) by using\nstate-of-the-art data analysis pipeline at WSI. The study will lastly perform the reconstruction of clonal\narchitecture in diagnostic biopsies by the use of Dirichlet process mixture model (DP) coupled with an\nMCMC sampler to perform Bayesian computations (Nik-Zainal et al, Cell 2012). Validation of predicted\nclone-originating genomic variants will be performed in vitro via standard Sanger DNA sequencing\nand/or FISH on the original FFPE biopsies. A final profiling of clinical features in patients with specific level\nof clonal heterogeneity will conclude the project, providing a proof-of-concept for the use of clonal\nreconstruction in PC diagnosis and proposing clonality as an additional component of diagnostics\ncomplexity.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005556","title":"Automated machine-learning approach for next generation profiling of sequence alterations, mutation burden, microsatellite instability, and structural variants in human cancers","description":"Sequence and structural alterations together with tumor mutation burden (TMB) and microsatellite instability (MSI) have been identified as biomarkers for the determination of response to targeted and immune checkpoint inhibitor therapies.  However, widespread clinical adoption of these biomarkers has historically been limited due to barriers such as evidence of clinical utility and reimbursement. We have developed 2.2 Mb targeted NGS system and an automated machine-learning analysis approach (PGDx elio™ tissue complete, ETC) that has been FDA cleared for examination of 500+ cancer-related genes and 68 mononucleotide repeats for identification of sequence and structural alterations, TMB, and MSI in solid cancers in a clinical setting.  We designed and trained this approach using sequence data from 4,174 cancers and &amp;gt;124,000 in silico alterations and evaluated the methodology in &amp;gt;2,550 tumor or non-cancerous normal samples.  Independent analyses of ETC sequence changes in 440 formalin fixed paraffin embedded (FFPE) tumor or cell line samples using MSK-IMPACT™, FoundationOne®, and ddPCR revealed a positive percent agreement (PPA) &amp;gt;97% with high sensitivity as low as 3% mutant allele fraction.  We observed high concordance between panel-wide and whole-exome TMB for 307 pan-cancer FFPE tumors (Pearson r=0.95, p &amp;lt; 0.0001) using samples with ≥20% tumor cellularity.  Comparison of the mutation context and repeat-based MSI approach in ETC with a multiplex MSI PCR assay in 223 samples revealed a PPA of 99% and negative predictive agreement (NPA) &amp;gt;99%.  We confirmed the accuracy and precision of TMB and MSI measurements across three independent laboratories (CV of &amp;lt;5% and average PPA &amp;gt;99%, respectively). Finally, evaluation of amplifications and translocations against DNA and RNA-based approaches exhibited &amp;gt;98% NPA and PPA of 86% and 82% respectively.  These results demonstrate high analytical performance for determination of sequence and structural changes, TMB, and MSI using a targeted NGS panel and provide a scalable and facile approach for evaluating these biomarkers in a clinical laboratory.","abstract":"Sequence and structural alterations together with tumor mutation burden (TMB) and microsatellite instability (MSI) have been identified as biomarkers for the determination of response to targeted and immune checkpoint inhibitor therapies.  However, widespread clinical adoption of these biomarkers has historically been limited due to barriers such as evidence of clinical utility and reimbursement. We have developed 2.2 Mb targeted NGS system and an automated machine-learning analysis approach (PGDx elio™ tissue complete, ETC) that has been FDA cleared for examination of 500+ cancer-related genes and 68 mononucleotide repeats for identification of sequence and structural alterations, TMB, and MSI in solid cancers in a clinical setting.  We designed and trained this approach using sequence data from 4,174 cancers and &amp;gt;124,000 in silico alterations and evaluated the methodology in &amp;gt;2,550 tumor or non-cancerous normal samples.  Independent analyses of ETC sequence changes in 440 formalin fixed paraffin embedded (FFPE) tumor or cell line samples using MSK-IMPACT™, FoundationOne®, and ddPCR revealed a positive percent agreement (PPA) &amp;gt;97% with high sensitivity as low as 3% mutant allele fraction.  We observed high concordance between panel-wide and whole-exome TMB for 307 pan-cancer FFPE tumors (Pearson r=0.95, p &amp;lt; 0.0001) using samples with ≥20% tumor cellularity.  Comparison of the mutation context and repeat-based MSI approach in ETC with a multiplex MSI PCR assay in 223 samples revealed a PPA of 99% and negative predictive agreement (NPA) &amp;gt;99%.  We confirmed the accuracy and precision of TMB and MSI measurements across three independent laboratories (CV of &amp;lt;5% and average PPA &amp;gt;99%, respectively). Finally, evaluation of amplifications and translocations against DNA and RNA-based approaches exhibited &amp;gt;98% NPA and PPA of 86% and 82% respectively.  These results demonstrate high analytical performance for determination of sequence and structural changes, TMB, and MSI using a targeted NGS panel and provide a scalable and facile approach for evaluating these biomarkers in a clinical laboratory.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-24T01:57:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005557","title":"NSCLC_WES___WGS","description":"The tumour microenvironment (TME) represents a complex cellular ecosystem that includes endothelial cell, fibroblasts, tumour cells, lymphoid cells, myeloid cells, etc. While the focus of this programme of work is on the characterisation of the myeloid compartment and MDSCs we will also examine interaction of these cells with TME cells in NSCLC. Finally, part of each tumour sample will be used for whole exome sequencing (WES) to evaluate tumour mutation burden (TMB).","abstract":"Tumour ecosystems represent sites enriched in distinct immune cell types and in the production of chemokines and cytokines. Myeloid cells are abundant within the tumour and their disease-promoting functions have been previously demonstrated. It is considered that tumour-derived factors promote functional “reprogramming” of myeloid progenitors towards myeloid-derived suppressor cells (MDSCs). We aim to use laser-capture microscopy (LCM) in an attempt to capture the clones from different areas of a particular tumour (capturing mild, moderate and severe stromal inflammation annotated by pathologists) across tumours from multiple patients. With this, we aim to identify a mutational clonal pattern and determine whether the clones present in tumour samples are distinct from healthy tissues","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005558","title":"Whole-transcriptome sequencing of hepatocellular carcinoma biopsies (TACE study)","description":"We performed a transcriptomic analysis of hepatocellular carcinomas (HCCs) and paired non-tumor biopsies to identify predictive biomarkers for response to transarterial chemoembolization (TACE). We identified several transcripts which are predictive of response to TACE.","abstract":"We performed a transcriptomic analysis of hepatocellular carcinomas (HCCs) and paired non-tumor biopsies to identify predictive biomarkers for response to transarterial chemoembolization (TACE). We identified several transcripts which are predictive of response to TACE.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-24T15:49:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005559","title":"WGS_of_healhy_mesothelial_cells_and_primary_mesothelima_cell_lines","description":"Mesothelioma is a rare and aggressive cancer associated with previous exposure to asbestos. Currently there are no effective treatments for mesothelioma and majority of patients will die within a year after diagnosis. Although a large number of preclinical and clinical trials assessed the efficacy of various therapuetic modes, none of the tested molecules entered the clinic. Thus, to better understand what drives mesothelioma carcinogenesis and to identify novel targets for therapy, here we aim at performing WGS of heathy mesothelial cells and a panel of mesothelioma cells lines. Primary mesothelial cell lines were established in prof. Marciniak lab from human pleural specimens, while primary mesothelioma cell lines were obtained from MesobanK. Both models constitute low passage cell lines and therefore should closely represent genetics of the original tissue.","abstract":"Mesothelioma is a rare and aggressive cancer associated with previous exposure to asbestos. Currently there are no effective treatments for mesothelioma and majority of patients will die within a year after diagnosis. Although a large number of preclinical and clinical trials assessed the efficacy of various therapuetic modes, none of the tested molecules entered the clinic. Thus, to better understand what drives mesothelioma carcinogenesis and to identify novel targets for therapy, here we aim at performing WGS of heathy mesothelial cells and a panel of mesothelioma cells lines. Primary mesothelial cell lines were established in prof. Marciniak lab from human pleural specimens, while primary mesothelioma cell lines were obtained from MesobanK. Both models constitute low passage cell lines and therefore should closely represent genetics of the original tissue.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-24T16:07:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005560","title":"Mitochondrial DNA sequencing of iPSC, parental cells, and iPSC derived cardiomyocytes","description":"The aim of this work was to analyze to which extent mitochondrial DNA (mtDNA) variants in human induced pluripotent stem cells (iPSC) originate from their parental cells or from de novo mutagenesis, and whether dynamics in variant heteroplasmy levels during prolonged expansion culture of iPSC are caused by inter- or intra-cellular selection or genetic drift. Hence, mtDNA of 26 early passage iPSC clones from, in total, 10 donors and the corresponding parental cell populations (here endothelial cells) were sequenced. Furthermore, 7 iPSC clones were expanded up to passage 50 and the change in variant heteroplasmy levels was monitored. Lastly, the effect of differentiation on the variant heteroplasmy levels was investigated during directed cardiomyocyte differentiation of 4 iPSC clones.","abstract":"The aim of this work was to analyze to which extent mitochondrial DNA (mtDNA) variants in human induced pluripotent stem cells (iPSC) originate from their parental cells or from de novo mutagenesis, and whether dynamics in variant heteroplasmy levels during prolonged expansion culture of iPSC are caused by inter- or intra-cellular selection or genetic drift. Hence, mtDNA of 26 early passage iPSC clones from, in total, 10 donors and the corresponding parental cell populations (here endothelial cells) were sequenced. Furthermore, 7 iPSC clones were expanded up to passage 50 and the change in variant heteroplasmy levels was monitored. Lastly, the effect of differentiation on the variant heteroplasmy levels was investigated during directed cardiomyocyte differentiation of 4 iPSC clones.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-26T13:16:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005561","title":"Genomic profiling of Follicular thyroid adenomas and carcinomas using exome-sequencing analyses","description":"While thyroid nodules per se are frequent (4%–50%), thyroid cancer is rare (∼5% of all thyroid nodules). The minimally invasive Fine Needle Aspiration Cytology (FNAC) is the current gold standard for the diagnosis thyroid nodule malignancy. However, proper discrimination of follicular neoplasias often require more invasive diagnostic techniques. To develop a novel molecular classification system for thyroid cancer malignancy, we performed an genomic profiling of 54 fresh frozen Follicular like thyroid samples using a whole exome sequencing approach (SureSelect V6 Target enrichment protocol and the Illumina Novaseq 6000 platform)","abstract":"While thyroid nodules per se are frequent (4%–50%), thyroid cancer is rare (∼5% of all thyroid nodules). The minimally invasive Fine Needle Aspiration Cytology (FNAC) is the current gold standard for the diagnosis thyroid nodule malignancy. However, proper discrimination of follicular neoplasias often require more invasive diagnostic techniques. To develop a novel molecular classification system for thyroid cancer malignancy, we performed an genomic profiling of 54 fresh frozen Follicular like thyroid samples using a whole exome sequencing approach (SureSelect V6 Target enrichment protocol and the Illumina Novaseq 6000 platform)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-26T23:02:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005562","title":"Jagged ends of plasma DNA (human)","description":"Jagged ends of plasma DNA (human)","abstract":"Jagged ends of plasma DNA (human)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-27T09:33:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005563","title":"Jagged ends of plasma DNA (mouse)","description":"Jagged ends of plasma DNA (mouse)","abstract":"Jagged ends of plasma DNA (mouse)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-27T09:37:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005564","title":"DNA methylation and RNA sequencing of brain-derived NeuN+ nuclei from fetuses with Down Syndrome","description":null,"abstract":"Down syndrome (DS) is a common (1 of 1000 live births) autosomal aneuploidy in humans, involving a trisomy of chromosome 21 and manifests as a wide range, though with variable penetrance, of phenotypic features and comorbidities, such as intellectual disability (ID), leukaemia and early onset Alzheimer disease. Epigenetic programming regulates gene expression and comprises features as histone modifications, microRNAs and lncRNAs and DNA methylation. In this study, we aimed to detect loci that are associated in particular with the aberrant early developing brain of DS in order to detect plausible loci that link to the ID characteristic of DS per se. We generated DNA methylation profiles (EPIC, Illumina) and transcriptomic profiles (RNAseq) from NeuN+ nuclei obtained from cerebrum sections of DS and control individuals at approximately 20 weeks gestational age. Data quality control was strictly applied, minimizing sample heterogeneity. We applied linear models to both data sets and additionally applied an integrative approach using both the DNA methylation and gene expression data. \n\nLarge-scale differences in DNA methylation and gene expression were observed across the entire genome, enriched in particular at chromosome 21. A substantial number of differentially methylated regions (DMRs) were replicated in a design matched previous report. Both separate analysis and integrative analyses of the DMRs and DEGs yielded large numbers of associated loci that could be linked to DS phenotypic characteristics, in particular atrium septum defects and intellectual disability.\n\nWe associated a large number of loci with aberrant cerebrum development in DS at the level of DNA methylation and gene expression that could potentially underlie the ID phenotype. Moreover, several other loci were linked to other DS phenotypic particular characteristics as well. Since epigenetic programming is susceptible for editing, our study may contribute to future steps to diminish the particular the ID characteristics of DS.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005565","title":"Transcriptomes of human CD4+ T lymphocytes - Metabolic project","description":"Human CD4+ T cells are essential mediators of immune responses. By altering the mitochondrial and metabolic states, we defined metabolic requirements of human CD4+ T cells for in vitro activation, expansion, and effector function. T cell activation and proliferation were reduced by inhibiting oxidative phosphorylation, while early cytokine production was maintained by either OXPHOS or glycolytic activity. Glucose deprivation in the presence of mild mitochondrial stress markedly reduced all three T cell functions, contrasting the exposure to resveratrol, an antioxidant and sirtuin-1 activator, which specifically inhibited cytokine production and T cell proliferation, but not T cell activation. Conditions that inhibited T cell activation were associated with the downregulation of 2′,5′-oligoadenylate synthetase genes via interferon response pathways. Our findings indicate that T cell function is grossly impaired by stressors combined with nutrient deprivation, suggesting that correcting nutrient availability, metabolic stress and/or the function of T cells in these conditions will improve the efficacy of T cell-based therapies.","abstract":"Human CD4+ T cells are essential mediators of immune responses. By altering the mitochondrial and metabolic states, we defined metabolic requirements of human CD4+ T cells for in vitro activation, expansion, and effector function. T cell activation and proliferation were reduced by inhibiting oxidative phosphorylation, while early cytokine production was maintained by either OXPHOS or glycolytic activity. Glucose deprivation in the presence of mild mitochondrial stress markedly reduced all three T cell functions, contrasting the exposure to resveratrol, an antioxidant and sirtuin-1 activator, which specifically inhibited cytokine production and T cell proliferation, but not T cell activation. Conditions that inhibited T cell activation were associated with the downregulation of 2′,5′-oligoadenylate synthetase genes via interferon response pathways. Our findings indicate that T cell function is grossly impaired by stressors combined with nutrient deprivation, suggesting that correcting nutrient availability, metabolic stress and/or the function of T cells in these conditions will improve the efficacy of T cell-based therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-27T12:10:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005566","title":"RNA-seq analysis of granulocytic progenitors derived from iPSC of two THC2 patients","description":null,"abstract":"The induced pluripotent cells were derived from CD34+ cells isolated from peripheral blood of two patients presenting with thrombocytopenia 2. \nThe iPSC were than differentiated toward granulocytic lineage and granulocyte progenitros were sorted on specific markers (CD43+CD11b+CD14-) and sequenced after RNA extraction. The data were compared to those obtained by the same protocol from normal control already published iPSC.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005567","title":"The genomic landscape of early stage ovarian high grade serous carcinoma","description":"To determine whether early-stage ovarian high grade serous carcinoma (HGSC) represents a distinct genomic entity, we collected samples from 43 patients with stage IA-IIA HGSC to identify potential differences in short genomic variants and copy number aberrations, and compared them to a cohort of 52 late-stage (stage IIIC-IV) cases. We found no significant differences in somatic mutations or focal copy number alterations between early-stage and late-stage cohorts. There was, however, a significant difference in both ploidy and copy number signature exposure between early and late-stage samples, with higher ploidy and signature 4 exposure in late-stage cases. Unsupervised hierarchical clustering revealed three clusters, which were prognostic. Together, our data suggest that early and late-stage HGSC share fundamental genomic features, but that late- stage disease appears distinct from early-stage, with evidence of whole genome duplication that may provide evolutionary benefit.","abstract":"To determine whether early-stage ovarian high grade serous carcinoma (HGSC) represents a distinct genomic entity, we collected samples from 43 patients with stage IA-IIA HGSC to identify potential differences in short genomic variants and copy number aberrations, and compared them to a cohort of 52 late-stage (stage IIIC-IV) cases. We found no significant differences in somatic mutations or focal copy number alterations between early-stage and late-stage cohorts. There was, however, a significant difference in both ploidy and copy number signature exposure between early and late-stage samples, with higher ploidy and signature 4 exposure in late-stage cases. Unsupervised hierarchical clustering revealed three clusters, which were prognostic. Together, our data suggest that early and late-stage HGSC share fundamental genomic features, but that late- stage disease appears distinct from early-stage, with evidence of whole genome duplication that may provide evolutionary benefit.","study_type":"Other","pubmed_ids":[35398881],"external_links":null,"is_released":true,"released_date":"2021-08-27T14:56:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005568","title":"Type I PRMT inhibition activates anti-viral mimicry response in triple negative breast cancer","description":null,"abstract":"Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and a lack of effective targeted therapies. Here, we undertook a screen of epigenetic chemical probes to systematically uncover the epigenetic regulators critical for TNBC growth. We identified MS023, an inhibitor of type I protein arginine methyltransferases (PRMTs), as having anti-tumor growth activity in TNBC in vitro and in vivo. Pathway analysis of TNBC cell lines indicates that the activation of interferon responses may prove crucial both functionally and as a biomarker in pre- and post-MS023 treatment. As a biomarker, this correlation is recapitulated in a panel of patient-derived organoids. Inhibition of type I PRMT triggers an interferon response through the antiviral defense pathway with the induction of double-stranded RNA (dsRNA). The dsRNA accumulation is derived, at least in part, from inverted-repeat Alus (IR-Alus), many of which are expressed from retained introns induced by MS023, which inhibits arginine methylation of RNA-binding proteins and alters mRNA splicing machinery. Together, our results represent a shift in understanding the anti-tumor mechanism of type I PRMT inhibitors and provide a rationale for the clinical translation of type I PRMT inhibitors.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005569","title":"Are children born after medical assisted reproduction at greater risk of having an increased de novo mutation rate?","description":"Introduction: De novo mutations (DNMs) play a prominent role in sporadic disorders with reduced fitness such as infertility and intellectual disability. Advanced paternal age is known to increase disease risk in offspring by increasing the number of DNMs in their genome. Less is known about the effect of assisted reproduction techniques (ART) on the number of DNMs in offspring. With the on-going trend of delayed parenthood more children are now born both from older fathers and through ART.\nMaterials and Methods: We investigated 49 trios (mother, father and child) and 2 quartets (mother, father and 2 siblings) divided into children born after spontaneous conception (n=18); born after in vitro fertilisation (IVF) (n=17) and born after intracytoplasmic sperm injection combined with testicular sperm extraction (ICSI-TESE) (n=18). Groups further divided by paternal age, young (&lt;35) or old (&gt;45 years of age at conception). Whole-genome sequencing was performed twice to independently detect and validate all DNMs in children.\nResults: A clear paternal age effect was observed, with 70 DNMs detected on average in children born to young fathers and 94 DNMs in those born to older fathers (p = 0.001). No significant differences were observed between different methods of conception (p = 1) with paternal age affecting all methods equally.\nConclusions: Paternal age, not method of conception, had a major effect on the observed number of DNMs in offspring. Given the role DNMs in disease risk, this negative result is good news for IVF and ICSI-TESE born children, if replicated in larger cohorts.","abstract":"Introduction: De novo mutations (DNMs) play a prominent role in sporadic disorders with reduced fitness such as infertility and intellectual disability. Advanced paternal age is known to increase disease risk in offspring by increasing the number of DNMs in their genome. Less is known about the effect of assisted reproduction techniques (ART) on the number of DNMs in offspring. With the on-going trend of delayed parenthood more children are now born both from older fathers and through ART.\nMaterials and Methods: We investigated 49 trios (mother, father and child) and 2 quartets (mother, father and 2 siblings) divided into children born after spontaneous conception (n=18); born after in vitro fertilisation (IVF) (n=17) and born after intracytoplasmic sperm injection combined with testicular sperm extraction (ICSI-TESE) (n=18). Groups further divided by paternal age, young (&lt;35) or old (&gt;45 years of age at conception). Whole-genome sequencing was performed twice to independently detect and validate all DNMs in children.\nResults: A clear paternal age effect was observed, with 70 DNMs detected on average in children born to young fathers and 94 DNMs in those born to older fathers (p = 0.001). No significant differences were observed between different methods of conception (p = 1) with paternal age affecting all methods equally.\nConclusions: Paternal age, not method of conception, had a major effect on the observed number of DNMs in offspring. Given the role DNMs in disease risk, this negative result is good news for IVF and ICSI-TESE born children, if replicated in larger cohorts.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-08-31T10:38:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005570","title":"NSCLC_WES___WGS","description":"The tumour microenvironment (TME) represents a complex cellular ecosystem that includes endothelial cell, fibroblasts, tumour cells, lymphoid cells, myeloid cells, etc. While the focus of this programme of work is on the characterisation of the myeloid compartment and MDSCs we will also examine interaction of these cells with TME cells in NSCLC. Finally, part of each tumour sample will be used for whole exome sequencing (WES) to evaluate tumour mutation burden (TMB).","abstract":"Tumour ecosystems represent sites enriched in distinct immune cell types and in the production of chemokines and cytokines. Myeloid cells are abundant within the tumour and their disease-promoting functions have been previously demonstrated. It is considered that tumour-derived factors promote functional “reprogramming” of myeloid progenitors towards myeloid-derived suppressor cells (MDSCs). We aim to use laser-capture microscopy (LCM) in an attempt to capture the clones from different areas of a particular tumour (capturing mild, moderate and severe stromal inflammation annotated by pathologists) across tumours from multiple patients. With this, we aim to identify a mutational clonal pattern and determine whether the clones present in tumour samples are distinct from healthy tissues.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005571","title":"HSC_colony_many_years_post_allogeneic_bone_marrow_transplant___Bait_set_for_BCL002","description":"This study looks at patients undergoing gene therapy for genetic blood and immune disorders, in particular sickle cell disease. From each patient, single blood HSPC colonies are grown from patient blood mononuclear cells,  bone marrow mononuclear cells, or CD34+ at multiple time points: pre gene transduction, post-transduction,  and post-infusion (at several time points). Whole-genome sequencing has been performed on DNA from these colonies and somatically-acquired mutations called. Using these mutations, a phylogeny of these cells can be inferred and further inferences can be made about the gene therapy transduction and engraftment steps. Looking for these mutations using a targeted approach will further inform our questions","abstract":"Blood stem cells are the fundamental component of all successful bone marrow transplantations – they are responsible for the longterm successful donor cell graft and the production of all mature blood cell lineages. Robust blood stem cell transplantation therefore is an essential requirement for all gene therapy applications that involve the blood and immune system (e.g., immunodeficiencies, anemias, etc). Often, the limiting factor for successful bone marrow transplantation is the ability to harvest a sufficient number of blood stem cells to ensure robust engraftment and the ability for the blood stem cells to retain their function outside the body while the gene target is being edited. Currently, stem cell number is estimated by the proportion of cells expressing a cell surface protein (CD34), but only a small minority of CD34+ cells are actually functional stem cells, meaning that more direct ways to measure stem cell numbers are essential. Furthermore, a better understanding of how many stem cells are harvested from patients (either directly or through stem cell mobilization protocols) and how many of these harvested stem cells contribute to donor cell production will be essential pieces of information for the better design of patient specific treatment protocols and may also lead to the development of better stem cell retention conditions. \n\nIn an effort to understand these questions in patients with sickle cell disease, we have assembled a multi-center, multi-disciplinary team of experts in gene therapy, stem cell biology, and genomics. Overall, this project builds on the recent discovery that whole genome sequencing approaches in blood stem and progenitor cells can be used to estimate the number of actively contributing blood stem cells in humans (Lee-Six et al., Nature 2018). More than 100,000 spontaneous, genome-wide somatic mutations were identified across 140 single-cell-derived blood stem and progenitor colonies from a healthy 59-year-old man. This allowed a family tree of relatedness to be constructed and population genetics approaches were applied to estimate the clonal dynamics of the stem cell pool. Stem cell population size was shown to grow steadily in early life and reach a stable plateau by adolescence with the number of stem cells actively making white blood cells at any one time being in the range of 50,000-200,000. \n\nThe overall aim of this project is to apply similar techniques in samples obtained from patients prior to and following autologous gene therapy for sickle cell disease in an effort to estimate the number of blood stem cells available for gene therapy. While the project outcomes will be focused on sickle cell disease, the low supply of transplantation material from sickle cell patients requires us to construct analysis pipelines on material from other diseases treated with gene therapy for longer periods (see below). Patient specific baseline data will be obtained from pre-transplantation samples including the construction of a phylogenetic tree of blood stem cell clones. The relative contributions (and origins) of successfully transduced blood stem cells will be determined by assessing samples taken post-transduction and post-transplantation, resulting in the estimation of stem cell numbers available for gene therapy in sickle cell patients","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005572","title":"Whole genome sequencing of a breast cancer cohort with known functional homologous recombination status","description":"Optimal patient selection for PARP inhibitors and double strand break (DSB) inducing chemotherapy is of great clinical importance. In principle, the use of these therapies can be extended beyond germline BRCA1/2 mutated cancers. Although several methods for detection of BRCA-like tumors have been developed, a golden standard is lacking. We have developed the RECAP test, a functional HR assay exploiting the formation of RAD51 foci in proliferating cells after ex vivo irradiation of fresh primary breast cancer (BrC) tissue. The RECAP test seems robust and has an advantage over genetic tests, due to its functional character for exploring the HR phenotype. Another type of HRD test is the BRCAness classifier, which is based on specific genomic patterns derived from copy number data of BRCA1/2 mutated BrCs that also occur in sporadic cancers. The BRCAness classifier is a robust test that is easily applicable in the clinic and has also been validated to predict in vivo response to high dose chemotherapy in clinical trials. More recently, a new HRD test based on genomic signatures which can be extracted from whole genome sequencing has been published, HRDetect. Studies comparing these different HRD tests within the same cohort of patients do not yet exist. Here, we have the unique opportunity to compare three HRD tests within the same cohort. We aim to compare three different HRD tests (RECAP, BRCAness classifier and HRDetect) within the same cohort of primary BrCs (n=41). As a secondary aim, we will analyze additional genetic alterations in HRD tumors (both BRCA-deficient and BRCA-proficient HRD tumors).","abstract":"Optimal patient selection for PARP inhibitors and double strand break (DSB) inducing chemotherapy is of great clinical importance. In principle, the use of these therapies can be extended beyond germline BRCA1/2 mutated cancers. Although several methods for detection of BRCA-like tumors have been developed, a golden standard is lacking. We have developed the RECAP test, a functional HR assay exploiting the formation of RAD51 foci in proliferating cells after ex vivo irradiation of fresh primary breast cancer (BrC) tissue. The RECAP test seems robust and has an advantage over genetic tests, due to its functional character for exploring the HR phenotype. Another type of HRD test is the BRCAness classifier, which is based on specific genomic patterns derived from copy number data of BRCA1/2 mutated BrCs that also occur in sporadic cancers. The BRCAness classifier is a robust test that is easily applicable in the clinic and has also been validated to predict in vivo response to high dose chemotherapy in clinical trials. More recently, a new HRD test based on genomic signatures which can be extracted from whole genome sequencing has been published, HRDetect. Studies comparing these different HRD tests within the same cohort of patients do not yet exist. Here, we have the unique opportunity to compare three HRD tests within the same cohort. We aim to compare three different HRD tests (RECAP, BRCAness classifier and HRDetect) within the same cohort of primary BrCs (n=41). As a secondary aim, we will analyze additional genetic alterations in HRD tumors (both BRCA-deficient and BRCA-proficient HRD tumors).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-01T09:12:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005573","title":"Expression signatures of NGLY1 deficiency","description":null,"abstract":"N-Glycanase 1 (NGLY1) deficiency is a rare and complex genetic disorder. Although recent studies have shed light on the molecular underpinnings of NGLY1 deficiency, a systematic characterization of gene and protein expression changes in patient-derived cells has been lacking. Here, we performed RNA-sequencing and mass spectrometry to determine the transcriptomes and proteomes of 66 cell lines representing 4 different cell types derived from 14 NGLY1 deficient patients and 17 controls. While gene and protein expression levels agreed well with each other, expression differences were more pronounced at the protein level. Although NGLY1 protein levels were up to 9.5-fold downregulated in patients compared to parent controls, depending on the genotype, NGLY1 protein was still detectable in all patient-derived lymphoblastoid cell lines. Consistent with the role of NGLY1 as a regulator of the transcription factor Nrf1, we observed a cell type-independent downregulation of proteasomal genes in NGLY1 deficient cells. In contrast, genes involved in ribosomal mRNA processing were upregulated in multiple cell types. In addition, we observed cell type-specific effects. For example, genes and proteins involved in glutathione synthesis, such as the glutamate-cystein ligase subunits GCLC and GCLM, were downregulated specifically in lymphoblastoid cells. We provide a web application that enables access to all results generated in this study at https://apps.embl.de/ngly1browser. This resource will guide future studies of NGLY1 deficiency in directions that are most relevant to patients.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-01T10:22:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005574","title":"HCA_Gut_Disease_Ulcerative_Colitis_WSSS_RNA","description":"Cell atlas of diseased human adult gut","abstract":"Human Cell Atlas for Gut - Adult RNA work. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005575","title":"The Microenvironment of Small Intestinal Neuroendocrine Tumours Contains Lymphocytes Capable of Recognition and Activation after Expansion","description":"Traditionally, immune evasion and immunotherapy have been studied in cancers with a high mutational load such as melanoma or lung cancer. In contrast, small intestinal neuroendocrine tumours (SINETs) present a low frequency of somatic mutations and are described as genetically stable tumours, rendering immunotherapies largely unchartered waters for SINET patients. SINETs frequently metastasise to the regional lymph nodes and liver at the time of diagnosis, and no curative treatments are currently available for patients with disseminated disease. Here, we characterised the immune landscape of SINET and demonstrated that tumour-infiltrating lymphocytes (TILs) can be expanded and activated during autologous tumour challenge. The composition of lymphocyte subsets was determined by immunophenotyping of the SINET microenvironment in one hepatic and six lymph node metastases. TILs from these metastases were successfully grown out, enabling immunophenotyping and assessment of PD-1 expression. Expansion of the TILs and exposure to autologous tumour cells in vitro resulted in increased T lymphocyte degranulation. This study provides insights into the largely unknown SINET immune landscape and reveals the anti-tumour reactivity of TILs, which might merit adoptive T cell transfer as a feasible treatment option for patients with SINET.","abstract":"Traditionally, immune evasion and immunotherapy have been studied in cancers with a high mutational load such as melanoma or lung cancer. In contrast, small intestinal neuroendocrine tumours (SINETs) present a low frequency of somatic mutations and are described as genetically stable tumours, rendering immunotherapies largely unchartered waters for SINET patients. SINETs frequently metastasise to the regional lymph nodes and liver at the time of diagnosis, and no curative treatments are currently available for patients with disseminated disease. Here, we characterised the immune landscape of SINET and demonstrated that tumour-infiltrating lymphocytes (TILs) can be expanded and activated during autologous tumour challenge. The composition of lymphocyte subsets was determined by immunophenotyping of the SINET microenvironment in one hepatic and six lymph node metastases. TILs from these metastases were successfully grown out, enabling immunophenotyping and assessment of PD-1 expression. Expansion of the TILs and exposure to autologous tumour cells in vitro resulted in increased T lymphocyte degranulation. This study provides insights into the largely unknown SINET immune landscape and reveals the anti-tumour reactivity of TILs, which might merit adoptive T cell transfer as a feasible treatment option for patients with SINET.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005576","title":"Fragmentomics of urinary cell-free DNA in nuclease knockout mouse models","description":null,"abstract":"Fragmentomics of urinary cell-free DNA in nuclease knockout mouse models","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005577","title":"Spatial Deconvolution of HER2-positive Breast Tumors","description":null,"abstract":"In the past decades, transcriptomic studies have revolutionized cancer treatment and diagnosis. However, tumor sequencing strategies typically result in loss of spatial information, critical to understand cell interactions and their functional relevance. To address this, we investigate spatial gene expression in HER2-positive breast tumors using Spatial Transcriptomics technology. We show that expression-based clustering enables data-driven tumor annotation and assessment of intra- and interpatient heterogeneity; from which we discover shared gene signatures for immune and tumor processes. By integration with single cell data, we spatially map tumor-associated cell types to find tertiary lymphoid-like structures, and a type I interferon response overlapping with regions of T-cell and macrophage subset colocalization. We construct a predictive model to infer presence of tertiary lymphoid-like structures, applicable across tissue types and technical platforms. Taken together, we combine different data modalities to define a high resolution map of cellular interactions in tumors and provide tools generalizing across tissues and diseases.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-02T12:54:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005578","title":"CRISPR_Cas___scRNAseq_in_human_iPSC","description":"This study will measure transcriptomes in undifferentiated genome edited induced pluripotent stem cells derived from multiple healthy donors, aimed to interrogate knockdown effect and variance in healthy individuals. We will perform CRISPR inhibition screens in multiple iPSC lines (~64 lines) for 3-6 days using several different gRNA libraries. Then single cells are sorted for dCas9 and gRNA presence after CRISPR/Cas9 perturbation, followed directly by 10x loading and single cell RNA library preparation using the 10x Genomics 5' v2 kit. The guide RNAs and the transcriptome are captured simultaneously from each single cell, and the gene expression and guide RNA libraries from multiple samples will be pooled together for sequencing. The entire project requested 72 lanes of NovaSeq S4. The first 16 lanes of Novaseq sequencing pertain to 64 of 10x inlets that are used for screens in 2 x 8 lines and 1x12 lines (2 timepoints) separately, and are covered under prelim WC10433. If the data is informative, CRISPRi screens in more individuals and single cell RNA libraries will be made in next step to establish perturbation effects for all genes in human iPSCs (under the same prelim WC10433).","abstract":"Multiple core questions in human genetics could be addressed by measuring transcriptomes of single cells in response to various genetic perturbations. Building on two rounds of successful pilot single cell CRISPR screen projects executed 2019-2021. Here we apply our approach at scale on multiple iPSC lines from healthy donors of the HIPSCI cohort with different genetic backgrounds, targeting large sets of genes with a range of fitness effects. We aim to 1) optimize experimental design of genome-wide knockdown screens in iPSCs; 2) establish the baseline measurement of magnitude and modifiability of gene perturbation effects on the transcriptome; 3) identify how genetic background influences the effect of gene knockdown on gene expression across individuals. To do so, we will perform CRISPR inhibition screens in multiple iPSC lines (~64 lines) for 3-6 days using several CRISPRi gRNA libraries. Then single cells are sorted for dCas9 and gRNA presence after CRISPR/Cas9 perturbation, followed directly by 10x loading. We will construct single cell RNA library preparation using the 10x Genomics 5' v2 kit. This will allow direct capture of guide RNAs and transcriptome simultaneously from each single cell of these donors. Then the gene expression and guide RNA libraries will be deep sequenced (total 72 lanes of NovaSeq S4) to reveal the effect of the different genetic perturbations on gene expression. These screens are part of an effort to establish gene regulatory networks in cell fitness and differentiation, and their differences across different individuals.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005579","title":"Mutation and Microsatellite Burden Predict Response to PD-1 Inhibition in Children with Germline DNA Replication Repair Deficiency: An Observational Registry Study","description":null,"abstract":"Cancers arising from germline DNA mismatch-repair or polymerase-proofreading deficiencies (MMRD and PPD) in children harbour the highest mutational and microsatellite insertion/deletion (MS-indel) burden in humans and are lethal due to inherent resistance to chemo-irradiation. Although immune checkpoint inhibitors (ICI) have failed to benefit children in previous studies, we hypothesized that hypermutation caused by MMRD and PPD will improve outcomes following ICI in these patients. Using an international consortium registry study, we report on the ICI treatment of 45 progressive/recurrent tumours from 38 patients, that revealed durable objective responses in the majority, culminating in 3-year survival of 41.4%. High mutation burden predicted response for ultra-hypermutant cancers (&gt;100 mutations/Mb) enriched for combined MMRD+PPD, while MS-indels predicted response in MMRD tumours with lower mutation burden (10-100 mutations/Mb). Further, both mechanisms were associated with increased immune infiltration even in “immunologically-cold” tumours such as gliomas, contributing to the favorable response. Pseudo-progression (flare) was common and associated with immune activation in both the tumour microenvironment and systemically. Further, patients with flare continuing ICI treatment achieved durable responses. Our study demonstrates improved survival for patients with tumours not previously known to respond to ICI, including CNS and synchronous cancers, and identifies the dual roles of mutation burden and MS-indels in predicting sustained responses to immunotherapy.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-03T13:24:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005580","title":"Single-cell characterization of anti-LAG3+anti-PD1 treatment in melanoma patients","description":null,"abstract":"In this study, we analyzed the lymphocyte response to anti-LAG3+anti-PD1 treatment (relatilimab+nivolumab, phase I, NCT01968109) in prior and 4- and 12-week posttherapy blood samples from 40 metastatic melanoma patients using scRNA+TCRαβ-seq, flow cytometry, TCRβ-seq, and serum protein profiling together with ex vivo functional validations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-03T20:33:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005581","title":"RNA-seq on neuroblastoma PDX model COG-N-519 treated with control miR-1283 and test miR-99b-5p mimics","description":"COG-N-519 primary neuroblastoma cells were innoculated by subcutaneous injection into NSG mice. When tumours reached a size of 100-200mm3 miRNAs conjugated to nanoparticles were injected intratumourally every 2 days for 1 week. 24 hr after the last injection, snap frozen tumour tissue was harvested for RNA extraction and RNA-seq analysis.","abstract":"COG-N-519 primary neuroblastoma cells were innoculated by subcutaneous injection into NSG mice. When tumours reached a size of 100-200mm3 miRNAs conjugated to nanoparticles were injected intratumourally every 2 days for 1 week. 24 hr after the last injection, snap frozen tumour tissue was harvested for RNA extraction and RNA-seq analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-04T12:50:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005582","title":"T cell receptors of pathogenic CD4 T cells  isolated by using distinct phenotypic markers in celiac disease","description":null,"abstract":"The main aim of this project is to test in the setting of celiac disease, whether gluten-specific CD4+ T cells may be isolated directly, solely based on this particular phenotype (Tpat) without the  use of HLA tetramers (Ttet). We performed high‐throughput sequencing of rearranged TCR‐α and TCR‐β genes of Ttet+/Tpat+, Ttet-/Tpat+ and Ttet-/Tpat- CD4+ cells from gut biopsies (exvivo) or that of T cell clones generated  from gut biopsies (invitro). The analysis of TCR sequencing data generated from this study will allow us to investigate different features of the TCR repertoire such as clonal expansions, sharing of sequences across donors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-05T22:00:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005583","title":"46 patients primary malignant glioma cohort in Chinese population","description":"We recruited 46 Chinese patients with primary malignant glioma. All the patients were analyzed with whole-exome sequencing (WES) and 27 of them were analyzed with RNA-seq. We compared the molecular features between patients in different WHO grades. We used six-month progression-free survival (PFS6) status to group glioblastoma (GBM) patients to a good and a poor survival compared two groups genomic profiles.","abstract":"We recruited 46 Chinese patients with primary malignant glioma. All the patients were analyzed with whole-exome sequencing (WES) and 27 of them were analyzed with RNA-seq. We compared the molecular features between patients in different WHO grades. We used six-month progression-free survival (PFS6) status to group glioblastoma (GBM) patients to a good and a poor survival compared two groups genomic profiles.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-06T03:32:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005584","title":"Genomics to select patients with metastatic breast cancer for targeted therapy (microarray_cytoscan)","description":"Cancer progression is driven in part by genomic alterations located in oncogenes or tumor suppressor genes. The genomic characterization of cancers has shown a large interpatient heterogeneity regarding the driver alterations, leading to the concept that generating a genomic profiling by multigene sequencing in patients with cancer could allow selecting effective targeted therapies. While this concept has been broadly implemented in daily practice, there is no evidence that such approach improves patient outcome, and how to optimally select the therapy to administer. A genomic profiling using next generation sequencing and copy number analyses was performed 1462 patients with Her2-non overexpressing metastatic breast cancer included in SAFIR02 Breast trial. 238 of these patients were randomized in two trials between a targeted therapy matched to genomic alteration and a maintenance chemotherapy. The trial shows that targeted therapies matched to genomics improves progression free survival (PFS) when genomic alterations are classified level I/II according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) (adjusted HR: 0.41, 90% CI: 0.27-0.61, p&lt;0.001), but not when alterations are classified beyond level II (unadjusted HR: 1.15, 95% CI: 0.76-1.75). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with mBC.","abstract":"Cancer progression is driven in part by genomic alterations located in oncogenes or tumor suppressor genes. The genomic characterization of cancers has shown a large interpatient heterogeneity regarding the driver alterations, leading to the concept that generating a genomic profiling by multigene sequencing in patients with cancer could allow selecting effective targeted therapies. While this concept has been broadly implemented in daily practice, there is no evidence that such approach improves patient outcome, and how to optimally select the therapy to administer. A genomic profiling using next generation sequencing and copy number analyses was performed 1462 patients with Her2-non overexpressing metastatic breast cancer included in SAFIR02 Breast trial. 238 of these patients were randomized in two trials between a targeted therapy matched to genomic alteration and a maintenance chemotherapy. The trial shows that targeted therapies matched to genomics improves progression free survival (PFS) when genomic alterations are classified level I/II according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) (adjusted HR: 0.41, 90% CI: 0.27-0.61, p&lt;0.001), but not when alterations are classified beyond level II (unadjusted HR: 1.15, 95% CI: 0.76-1.75). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with mBC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-06T10:00:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005585","title":"Genomics to select patients with metastatic breast cancer for targeted therapy (NGS target)","description":"Cancer progression is driven in part by genomic alterations located in oncogenes or tumor suppressor genes. The genomic characterization of cancers has shown a large interpatient heterogeneity regarding the driver alterations, leading to the concept that generating a genomic profiling by multigene sequencing in patients with cancer could allow selecting effective targeted therapies. While this concept has been broadly implemented in daily practice, there is no evidence that such approach improves patient outcome, and how to optimally select the therapy to administer. A genomic profiling using next generation sequencing and copy number analyses was performed 1462 patients with Her2-non overexpressing metastatic breast cancer included in SAFIR02 Breast trial. 238 of these patients were randomized in two trials between a targeted therapy matched to genomic alteration and a maintenance chemotherapy. The trial shows that targeted therapies matched to genomics improves progression free survival (PFS) when genomic alterations are classified level I/II according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) (adjusted HR: 0.41, 90% CI: 0.27-0.61, p&lt;0.001), but not when alterations are classified beyond level II (unadjusted HR: 1.15, 95% CI: 0.76-1.75). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with mBC.","abstract":"Cancer progression is driven in part by genomic alterations located in oncogenes or tumor suppressor genes. The genomic characterization of cancers has shown a large interpatient heterogeneity regarding the driver alterations, leading to the concept that generating a genomic profiling by multigene sequencing in patients with cancer could allow selecting effective targeted therapies. While this concept has been broadly implemented in daily practice, there is no evidence that such approach improves patient outcome, and how to optimally select the therapy to administer. A genomic profiling using next generation sequencing and copy number analyses was performed 1462 patients with Her2-non overexpressing metastatic breast cancer included in SAFIR02 Breast trial. 238 of these patients were randomized in two trials between a targeted therapy matched to genomic alteration and a maintenance chemotherapy. The trial shows that targeted therapies matched to genomics improves progression free survival (PFS) when genomic alterations are classified level I/II according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) (adjusted HR: 0.41, 90% CI: 0.27-0.61, p&lt;0.001), but not when alterations are classified beyond level II (unadjusted HR: 1.15, 95% CI: 0.76-1.75). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with mBC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005586","title":"Genomics to select patients with metastatic breast cancer for targeted therapy (microarray_oncoscan)","description":"Cancer progression is driven in part by genomic alterations located in oncogenes or tumor suppressor genes. The genomic characterization of cancers has shown a large interpatient heterogeneity regarding the driver alterations, leading to the concept that generating a genomic profiling by multigene sequencing in patients with cancer could allow selecting effective targeted therapies. While this concept has been broadly implemented in daily practice, there is no evidence that such approach improves patient outcome, and how to optimally select the therapy to administer. A genomic profiling using next generation sequencing and copy number analyses was performed 1462 patients with Her2-non overexpressing metastatic breast cancer included in SAFIR02 Breast trial. 238 of these patients were randomized in two trials between a targeted therapy matched to genomic alteration and a maintenance chemotherapy. The trial shows that targeted therapies matched to genomics improves progression free survival (PFS) when genomic alterations are classified level I/II according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) (adjusted HR: 0.41, 90% CI: 0.27-0.61, p&lt;0.001), but not when alterations are classified beyond level II (unadjusted HR: 1.15, 95% CI: 0.76-1.75). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with mBC.","abstract":"Cancer progression is driven in part by genomic alterations located in oncogenes or tumor suppressor genes. The genomic characterization of cancers has shown a large interpatient heterogeneity regarding the driver alterations, leading to the concept that generating a genomic profiling by multigene sequencing in patients with cancer could allow selecting effective targeted therapies. While this concept has been broadly implemented in daily practice, there is no evidence that such approach improves patient outcome, and how to optimally select the therapy to administer. A genomic profiling using next generation sequencing and copy number analyses was performed 1462 patients with Her2-non overexpressing metastatic breast cancer included in SAFIR02 Breast trial. 238 of these patients were randomized in two trials between a targeted therapy matched to genomic alteration and a maintenance chemotherapy. The trial shows that targeted therapies matched to genomics improves progression free survival (PFS) when genomic alterations are classified level I/II according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) (adjusted HR: 0.41, 90% CI: 0.27-0.61, p&lt;0.001), but not when alterations are classified beyond level II (unadjusted HR: 1.15, 95% CI: 0.76-1.75). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with mBC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-06T10:01:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005587","title":"Genomics to select patients with metastatic breast cancer for targeted therapy (microarray_agilent)","description":"Cancer progression is driven in part by genomic alterations located in oncogenes or tumor suppressor genes. The genomic characterization of cancers has shown a large interpatient heterogeneity regarding the driver alterations, leading to the concept that generating a genomic profiling by multigene sequencing in patients with cancer could allow selecting effective targeted therapies. While this concept has been broadly implemented in daily practice, there is no evidence that such approach improves patient outcome, and how to optimally select the therapy to administer. A genomic profiling using next generation sequencing and copy number analyses was performed 1462 patients with Her2-non overexpressing metastatic breast cancer included in SAFIR02 Breast trial. 238 of these patients were randomized in two trials between a targeted therapy matched to genomic alteration and a maintenance chemotherapy. The trial shows that targeted therapies matched to genomics improves progression free survival (PFS) when genomic alterations are classified level I/II according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) (adjusted HR: 0.41, 90% CI: 0.27-0.61, p&lt;0.001), but not when alterations are classified beyond level II (unadjusted HR: 1.15, 95% CI: 0.76-1.75). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with mBC.","abstract":"Cancer progression is driven in part by genomic alterations located in oncogenes or tumor suppressor genes. The genomic characterization of cancers has shown a large interpatient heterogeneity regarding the driver alterations, leading to the concept that generating a genomic profiling by multigene sequencing in patients with cancer could allow selecting effective targeted therapies. While this concept has been broadly implemented in daily practice, there is no evidence that such approach improves patient outcome, and how to optimally select the therapy to administer. A genomic profiling using next generation sequencing and copy number analyses was performed 1462 patients with Her2-non overexpressing metastatic breast cancer included in SAFIR02 Breast trial. 238 of these patients were randomized in two trials between a targeted therapy matched to genomic alteration and a maintenance chemotherapy. The trial shows that targeted therapies matched to genomics improves progression free survival (PFS) when genomic alterations are classified level I/II according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) (adjusted HR: 0.41, 90% CI: 0.27-0.61, p&lt;0.001), but not when alterations are classified beyond level II (unadjusted HR: 1.15, 95% CI: 0.76-1.75). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with mBC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-06T10:01:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005588","title":"RNA-sequencing of tumors from 45 patients with recurrent or metastatic gastric cancer treated with immune checkpoint inhibitors","description":"Genomic profiling can provide prognostic and predictive information to guide clinical care. Biomarkers that reliably predict patient response to chemotherapy and immune checkpoint inhibition in gastric cancer are lacking. In this work, we used our machine learning algorithm NTriPath to identify a gastric-cancer specific 32-gene signature. Using unsupervised clustering on expression levels of these 32 genes in tumors from 567 patients, we identified four molecular subtypes that were prognostic for survival. We then built a support vector machine with linear kernel and the binary classifier to generate a risk score that is prognostic for 5-year overall survival and validated the risk score using three independent datasets. We also found that the molecular subtypes predicted response to adjuvant 5-fluorouracil and platinum after gastrectomy and immune checkpoint inhibitors in patients with metastatic or recurrent disease. The 32-gene signature is a promising prognostic and predictive biomarker to guide the clinical care of gastric cancer patients and should be validated in a prospective manner.\n\nThis EGA archive includes both St.Mary hospital cohort samples (n=28) and Yonsei immunotherapy patient samples (n=17).","abstract":"Genomic profiling can provide prognostic and predictive information to guide clinical care. Biomarkers that reliably predict patient response to chemotherapy and immune checkpoint inhibition in gastric cancer are lacking. In this work, we used our machine learning algorithm NTriPath to identify a gastric-cancer specific 32-gene signature. Using unsupervised clustering on expression levels of these 32 genes in tumors from 567 patients, we identified four molecular subtypes that were prognostic for survival. We then built a support vector machine with linear kernel and the binary classifier to generate a risk score that is prognostic for 5-year overall survival and validated the risk score using three independent datasets. We also found that the molecular subtypes predicted response to adjuvant 5-fluorouracil and platinum after gastrectomy and immune checkpoint inhibitors in patients with metastatic or recurrent disease. The 32-gene signature is a promising prognostic and predictive biomarker to guide the clinical care of gastric cancer patients and should be validated in a prospective manner.\n\nThis EGA archive includes both St.Mary hospital cohort samples (n=28) and Yonsei immunotherapy patient samples (n=17).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-06T16:45:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005589","title":"Benchmarking DIA-type Proteomics Using Large-Scale Inter-Patient Heterogeneity Dataset","description":"Benchmarking Proteomics Quantitation in DIA-type data using real patient material to create a benchmark dataset comprising inter-patient heterogeneity","abstract":"Benchmarking Proteomics Quantitation in DIA-type data using real patient material to create a benchmark dataset comprising inter-patient heterogeneity","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-06T19:27:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005590","title":"CERT1 mutational spectra","description":null,"abstract":"Determine putative deleterious mutations in CERT1 gene.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005591","title":"Synthetic data - Genome in a Bottle","description":"In May, the National Institute of Standards and Technology (NIST) released its first genome in a bottle, a reference sample of DNA for validating human genome sequences. This so-called truth sequence comes from a decades-old sample donated by a Utah woman for (other) research purposes (NA12878 cell line), which, over the years, has been one of the most studied, and hence best-characterized, human samples. Seeing genomic medicine moving toward mainstream healthcare, researchers at NIST recognized the need for a reference human genome and assembled a private-public consortium in 2012 to create one. As detailed in a 2014 Nature Biotechnology paper (Nat. Biotechnol.32, 246–251, 2014), the group integrated and arbitrated among sequences from 14 data sets, five sequencing technologies, seven read mappers and three variant callers.","abstract":"In May, the National Institute of Standards and Technology (NIST) released its first genome in a bottle, a reference sample of DNA for validating human genome sequences. This so-called truth sequence comes from a decades-old sample donated by a Utah woman for (other) research purposes (NA12878 cell line), which, over the years, has been one of the most studied, and hence best-characterized, human samples. Seeing genomic medicine moving toward mainstream healthcare, researchers at NIST recognized the need for a reference human genome and assembled a private-public consortium in 2012 to create one. As detailed in a 2014 Nature Biotechnology paper (Nat. Biotechnol.32, 246–251, 2014), the group integrated and arbitrated among sequences from 14 data sets, five sequencing technologies, seven read mappers and three variant callers.","study_type":"Other","pubmed_ids":[24531798,27271295,30858580,30936564],"external_links":null,"is_released":true,"released_date":"2021-09-07T15:19:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005592","title":"Serial assessment of measurable residual disease in medulloblastoma liquid biopsies","description":"Nearly one-third of children with medulloblastoma, a malignant embryonal tumor of the cerebellum, succumb to their disease. Conventional response monitoring by imaging and cerebrospinal fluid (CSF) cytology remains challenging and a marker for measurable residual disease (MRD) is lacking. Here, we show the clinical utility of CSF-derived cell-free DNA (cfDNA) as a biomarker of MRD in  serial samples collected from children with medulloblastoma (123 patients, 476 samples) enrolled on a prospective trial. Using low-coverage whole-genome sequencing, tumor-associated copy-number variations (CNVs) in CSF-derived cfDNA are investigated as an MRD surrogate. MRD is detected at baseline in 85% and 54% of patients with metastatic and localized disease, respectively. The number of MRD-positive patients decline with therapy, yet those with persistent MRD have significantly higher risk of progression. Importantly, MRD detection precedes radiographic progression in half who relapse. Our findings advocate for the prospective assessment of CSF-derived liquid biopsies in future trials for medulloblastoma.","abstract":"Nearly one-third of children with medulloblastoma, a malignant embryonal tumor of the cerebellum, succumb to their disease. Conventional response monitoring by imaging and cerebrospinal fluid (CSF) cytology remains challenging and a marker for measurable residual disease (MRD) is lacking. Here, we show the clinical utility of CSF-derived cell-free DNA (cfDNA) as a biomarker of MRD in  serial samples collected from children with medulloblastoma (123 patients, 476 samples) enrolled on a prospective trial. Using low-coverage whole-genome sequencing, tumor-associated copy-number variations (CNVs) in CSF-derived cfDNA are investigated as an MRD surrogate. MRD is detected at baseline in 85% and 54% of patients with metastatic and localized disease, respectively. The number of MRD-positive patients decline with therapy, yet those with persistent MRD have significantly higher risk of progression. Importantly, MRD detection precedes radiographic progression in half who relapse. Our findings advocate for the prospective assessment of CSF-derived liquid biopsies in future trials for medulloblastoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-07T20:39:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005593","title":"Single-cell proteo-genomic reference maps of the human hematopoietic system","description":"We have generated high content single-cell proteo-genomic reference maps of human blood and bone marrow that quantitatively link the expression of up to 197 surface markers to cellular identities and biological processes across all major hematopoietic cell types in healthy aging and leukemia. Please note raw and integrated gene expression data, cell type annotation, metadata and dimensionality reduction are available as Seurat v3 objects through figshare. Access links are https://figshare.com/s/0fda29b169c719223ee3 (97 surface marker, 9 individuals dataset), https://figshare.com/s/313b5739ff469dac8c01 (197 surface marker, bone marrow and blood dataset), https://figshare.com/s/901bcddb9ee18e226031 (97 surface markers and whole transcriptome dataset) and https://figshare.com/s/24e10bf129fae1918316 (97 surface marker, 15 AML datasets).","abstract":"We have generated high content single-cell proteo-genomic reference maps of human blood and bone marrow that quantitatively link the expression of up to 197 surface markers to cellular identities and biological processes across all major hematopoietic cell types in healthy aging and leukemia. Please note raw and integrated gene expression data, cell type annotation, metadata and dimensionality reduction are available as Seurat v3 objects through figshare. Access links are https://figshare.com/s/0fda29b169c719223ee3 (97 surface marker, 9 individuals dataset), https://figshare.com/s/313b5739ff469dac8c01 (197 surface marker, bone marrow and blood dataset), https://figshare.com/s/901bcddb9ee18e226031 (97 surface markers and whole transcriptome dataset) and https://figshare.com/s/24e10bf129fae1918316 (97 surface marker, 15 AML datasets).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-09T09:07:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005594","title":"Myeloid cell programming in patients with non-medullary thyroid carcinoma","description":null,"abstract":"Immunotherapy has emerged in the last decade from an unfulfilled promise to a mainstay cancer treatment next to chemo- or radiotherapy. Accumulating evidence from the last years shows however that cells of the innate immune system are also crucial components of the immune response to cancer. In this study, we consider the crucial role of myeloid cells by integrating transcriptional and functional analysis of circulating myeloid cells and their bone marrow progenitors to characterise the spectrum of immune cell states in patients with thyroid cancer and multinodal goiter. Additionally, we assessed the effects of treatment with surgery and 131I on myeloid cells and their tumor suppressive phenotype.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-09T10:54:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005595","title":"46 patients primary malignant glioma cohort in Chinese population","description":"We recruited 46 Chinese patients with primary malignant glioma. All the patients were analyzed with whole-exome sequencing (WES) and 27 of them were analyzed with RNA-seq. We compared the molecular features between patients in different WHO grades. We used six-month progression-free survival (PFS6) status to group glioblastoma (GBM) patients to a good and a poor survival compared two groups genomic profiles.","abstract":"We recruited 46 Chinese patients with primary malignant glioma. All the patients were analyzed with whole-exome sequencing (WES) and 27 of them were analyzed with RNA-seq. We compared the molecular features between patients in different WHO grades. We used six-month progression-free survival (PFS6) status to group glioblastoma (GBM) patients to a good and a poor survival compared two groups genomic profiles.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005596","title":"Genetics and therapeutic responses to TIL therapy of pancreatic cancer PDX models","description":"Pancreatic cancer is the 7th leading cause of cancer-related deaths worldwide. Checkpoint immunotherapy has not yet showed encouraging results in pancreatic cancer possibly owing to a poor immunogenicity and/or an immune suppressive microenvironment. The aim of this study was to develop patient-derived xenografts (PDX) models and to assess if autologous tumor-infiltrating lymphocytes (TILs) would have anti-tumoral activity in pancreatic cancer. Tumor biopsies from 29 patients were subcutaneously transplanted into NOG mice. Tumor growths were confirmed in 11 out of 29 transplantations. The PDX tumors histologically resembled their original biopsies, but since stromal cells in the PDX model tumors were from mouse, their gene expression differed from the original biopsies. Immune checkpoint ligands other than PD-L1 were expressed in pancreatic cancers but PD-L1 was rarely expressed. One of the three tumors that did express PD-L1 was an adenosquamous cancer and another had a mismatch repair deficiency. TILs were expanded from six tumors and were injected into NOG or human interleukin-2 transgenic-NOG (hIL2-NOG) mice carrying PDX tumors. Regression of tumors could be verified in hIL2-NOG mice in 3 of the 6 PDX models treated with autologous TILs, including the adenosquamous PDX model. In conclusion, PDX models of pancreatic cancer can be used to learn more about tumor characteristics and biomarkers, and to evaluate responses to ACT and combination therapies. The major benefit of the model is that modifications of T cells can be tested in an autologous humanized mouse model to gain preclinical data to support the initiation of a clinical trial.","abstract":"Pancreatic cancer is the 7th leading cause of cancer-related deaths worldwide. Checkpoint immunotherapy has not yet showed encouraging results in pancreatic cancer possibly owing to a poor immunogenicity and/or an immune suppressive microenvironment. The aim of this study was to develop patient-derived xenografts (PDX) models and to assess if autologous tumor-infiltrating lymphocytes (TILs) would have anti-tumoral activity in pancreatic cancer. Tumor biopsies from 29 patients were subcutaneously transplanted into NOG mice. Tumor growths were confirmed in 11 out of 29 transplantations. The PDX tumors histologically resembled their original biopsies, but since stromal cells in the PDX model tumors were from mouse, their gene expression differed from the original biopsies. Immune checkpoint ligands other than PD-L1 were expressed in pancreatic cancers but PD-L1 was rarely expressed. One of the three tumors that did express PD-L1 was an adenosquamous cancer and another had a mismatch repair deficiency. TILs were expanded from six tumors and were injected into NOG or human interleukin-2 transgenic-NOG (hIL2-NOG) mice carrying PDX tumors. Regression of tumors could be verified in hIL2-NOG mice in 3 of the 6 PDX models treated with autologous TILs, including the adenosquamous PDX model. In conclusion, PDX models of pancreatic cancer can be used to learn more about tumor characteristics and biomarkers, and to evaluate responses to ACT and combination therapies. The major benefit of the model is that modifications of T cells can be tested in an autologous humanized mouse model to gain preclinical data to support the initiation of a clinical trial.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-10T10:29:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005597","title":"Patient data used in FLTseq paper","description":"Apply newly developed FLT-seq protocol and package FLAMES on a primary patient sample","abstract":"Apply newly developed FLT-seq protocol and package FLAMES on a primary patient sample","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-12T08:04:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005598","title":"The evolutionary dynamics of human colorectal cancer using single-gland spatial multi-omic profiling of DNA, RNA and chromatin.","description":null,"abstract":"Deciphering the mechanisms of colorectal cancer growth, progression and dissemination in each individual patient,","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005599","title":"Human skeletal muscle CD90+ fibro-adipogenic progenitors are associated with muscle degeneration in type 2 diabetic patients","description":null,"abstract":"Aging and type 2 diabetes mellitus (T2DM) are associated with impaired skeletal muscle function and degeneration of the skeletal muscle microenvironment. However, the origin and mechanisms underlying the degeneration are not well described in human skeletal muscle. Here we show that skeletal muscles of T2DM patients exhibit pathological degenerative remodeling of the extracellular matrix that was associated with a selective increase of a subpopulation of fibro-adipogenic progenitors (FAPs) marked by expression of THY1 (CD90).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-13T15:12:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005600","title":"Osteosarcoma sequencing data","description":"This study shares DNA and RNA sequencing data from embryonal rhadbomyosarcoma patients","abstract":"This study shares DNA and RNA sequencing data from embryonal rhadbomyosarcoma patients","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-13T17:59:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005601","title":"Absolute copy number fitting from shallow whole genome sequencing data","description":null,"abstract":"Low-coverage or shallow whole genome sequencing (sWGS) approaches can efficiently detect somatic copy number aberrations (SCNAs) at low cost. This is clinically important for many cancers, in particular cancers with severe chromosomal instability (CIN) that frequently lack actionable point mutations and are characterised by poor disease outcome. Absolute copy number (ACN), measured in DNA copies per cancer cell, is required for meaningful comparisons between copy number states, but is challenging to estimate and in practice often requires manual curation. Using a total of 60 cancer cell lines, 148 patient-derived xenograft (PDX) and 142 clinical tissue samples, we evaluate the performance of available tools for obtaining ACN from sWGS. We provide a validated and refined tool called Rascal (relative to absolute copy number scaling) that provides improved fitting algorithms and enables interactive visualisation of copy number profiles. These approaches are highly applicable to both pre-clinical and translational research studies on SCNA-driven cancers and provide more robust ACN fits from sWGS data than currently available tools.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-13T18:00:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005602","title":"Neuroblastoma sequencing data","description":"This study shares tumor and normal DNA for a patient with neuroblastoma","abstract":"This study shares tumor and normal DNA for a patient with neuroblastoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-13T18:21:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005603","title":"High-resolution analysis for urinary DNA jagged ends","description":"High-resolution analysis for urinary DNA jagged ends","abstract":"High-resolution analysis for urinary DNA jagged ends","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-14T10:15:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005604","title":"Berlin Neuroblastoma Dataset Update 2021","description":null,"abstract":"Circular RNAs (circRNAs), a noncoding RNA class originating from alternative splicing, are highly abundant in neural tissues and were shown to regulate gene expression e.g. by interacting with microRNAs and RNA-binding proteins. Neuroblastoma is an embryonal neoplasia, which arises from undifferentiated neural crest cells. Here, we aimed to explore, whether circRNAs influence the pathogenesis of high-risk neuroblastoma. We performed whole-transcriptome sequencing of 104 primary neuroblastoma samples of all risk-groups and identified 5,203 unique circRNAs involving 2,302 genes. Candidate circRNA expression did not correlate with host gene expression, indicating independent regulatory mechanisms. circRNAs were significantly downregulated in the MYCN-amplified high-risk tumors. These findings were independently reproduced in a tetracycline-inducible MYCN-overexpression system based on a non MYCN-amplified neuroblastoma cell line, suggesting that MYCN drives this global circRNA repression. We identified the RNA helicase DHX9 as a mediator of this global suppressive effect of MYCN on circRNAs. Comparing our RNA sequencing data with other cancers and controls revealed a circRNA subset specifically upregulated in neuroblastoma that included a circRNA derived from the ARID1A tumor suppressor gene. Specific circARID1A knockdown resulted in reduced proliferation, cell numbers and viability, prompted apoptosis and induced a differentiated phenotype. Neither knockdown, nor overexpression of circARID1A influenced ARID1A mRNA and protein levels significantly. To dissect the potential mode of function, we performed a pulldown assay with subsequent mass spectrometry. We identified the RNA-binding protein KHSRP as an interaction partner that participates in the mechanism of action of circARID1A. In summary, this study highlights an important role of circRNAs in neuroblastoma biology and may establish this RNA class as a future therapeutic target and biomarker.","study_type":"Cancer Genomics","pubmed_ids":[37402719],"external_links":null,"is_released":true,"released_date":"2021-09-14T15:57:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005605","title":"Application of Hi-C sequencing to detect structural variants in B-cell acute lymphoblastic leukemia","description":"Large structural variants are easily detected by Hi-C sequencing as strong, distant signals on a Hi-C contact map. Translocations are frequently evident in B-ALL and accurate identification of these translocations can guide clinical treatment options. Here were apply shallow Hi-C sequencing as an unbiased, cost-effective approach to identify translocations among B-ALL patients.","abstract":"Large structural variants are easily detected by Hi-C sequencing as strong, distant signals on a Hi-C contact map. Translocations are frequently evident in B-ALL and accurate identification of these translocations can guide clinical treatment options. Here were apply shallow Hi-C sequencing as an unbiased, cost-effective approach to identify translocations among B-ALL patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-14T17:53:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005606","title":"SNP array study in Autism Spectrum Disorder patients","description":"The aim of this study was to investigate two ancestral inversions (inv17q21.31 and inv8p23.1) in Autism Spectrum Disorder (ASD) patients. We have performed SNP array in order to genotype these inversions using the package scoreInvHap.","abstract":"The aim of this study was to investigate two ancestral inversions (inv17q21.31 and inv8p23.1) in Autism Spectrum Disorder (ASD) patients. We have performed SNP array in order to genotype these inversions using the package scoreInvHap.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-16T13:12:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005607","title":"Exploring_The_Landscape_Of_Somatic_Mutations_In_Human_Alveolar_Cells","description":"This study aims to characterize the genomic landscape of single-cell derived organoids from lung tissue of normal alveolar cells from patients with various smoking histories. Single-cell organoids have been created from patients that underwent broncoscopy, similar to the methodology used in previous projects including the work published by Yoshida and colleagues (https://www.nature.com/articles/s41586-020-1961-1/). Here, we will follow-up on this work by characterizing organoids from alveolar cells instead of squamous epithelium in order to determine the landscape of genomic alterations in human alveolar cells.","abstract":"This study aims to characterize the genomic landscape of single-cell derived organoids from lung tissue of normal alveolar cells from patients with various smoking histories. Single-cell organoids have been created from patients that underwent broncoscopy, similar to the methodology used in previous projects including the work published by Yoshida and colleagues (https://www.nature.com/articles/s41586-020-1961-1/). Here, we will follow-up on this work by characterizing organoids from alveolar cells instead of squamous epithelium in order to determine the landscape of genomic alterations in human alveolar cells.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005608","title":"DNA methylation calling tools for Oxford Nanopore sequencing: a survey and human epigenome-wide evaluation","description":"Background:  Nanopore long-read sequencing technology greatly expands the capacity of long-range, single-molecule DNA-modification detection. A growing number of analytical tools have been developed to detect DNA methylation from nanopore sequencing reads. Here, we assess the performance of different methylation-calling tools to provide a systematic evaluation to guide researchers performing human epigenome-wide studies. \nResults:  We compare seven analytic tools for detecting DNA methylation from nanopore long-read sequencing data generated from human natural DNA at a whole genome scale. We evaluate the per-read and per-site performance of CpG methylation prediction across different genomic contexts, CpG site coverage, and computational resources consumed by each tool. The seven tools exhibit different performances across the evaluation criteria. We show that the methylation prediction at regions with discordant DNA methylation patterns, intergenic regions, low CG density regions, and repetitive regions show room for improvement across all tools. Furthermore, we demonstrate that 5hmC levels at least partly contribute to the discrepancy between bisulfite and nanopore sequencing. Lastly, we provide an online DNA methylation database ( https://nanome.jax.org ) to display the DNA methylation levels detected by nanopore sequencing and bisulfite sequencing data across different genomic contexts. \nConclusions:  Our study is the first systematic benchmark of computational methods for the detection of mammalian whole-genome DNA modifications in nanopore sequencing. We provide a broad foundation for cross-platform standardization and an evaluation of analytical tools designed for genome-scale modified-base detection using nanopore sequencing","abstract":"Background:  Nanopore long-read sequencing technology greatly expands the capacity of long-range, single-molecule DNA-modification detection. A growing number of analytical tools have been developed to detect DNA methylation from nanopore sequencing reads. Here, we assess the performance of different methylation-calling tools to provide a systematic evaluation to guide researchers performing human epigenome-wide studies. \nResults:  We compare seven analytic tools for detecting DNA methylation from nanopore long-read sequencing data generated from human natural DNA at a whole genome scale. We evaluate the per-read and per-site performance of CpG methylation prediction across different genomic contexts, CpG site coverage, and computational resources consumed by each tool. The seven tools exhibit different performances across the evaluation criteria. We show that the methylation prediction at regions with discordant DNA methylation patterns, intergenic regions, low CG density regions, and repetitive regions show room for improvement across all tools. Furthermore, we demonstrate that 5hmC levels at least partly contribute to the discrepancy between bisulfite and nanopore sequencing. Lastly, we provide an online DNA methylation database ( https://nanome.jax.org ) to display the DNA methylation levels detected by nanopore sequencing and bisulfite sequencing data across different genomic contexts. \nConclusions:  Our study is the first systematic benchmark of computational methods for the detection of mammalian whole-genome DNA modifications in nanopore sequencing. We provide a broad foundation for cross-platform standardization and an evaluation of analytical tools designed for genome-scale modified-base detection using nanopore sequencing","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005609","title":"Functional_changes_associated_with_drivers_in_chronic_liver_disease__VISIUM_","description":"Recently, recurrent mutations in genes involved in lipid metabolism and insulin pathway have been identified in the liver of patients with non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ARLD). While preliminary data suggests that these mutations are pathogenic and may be contributing to disease phenotype, the functional consequences of these abberrations are not fully understood. This study will aim to characterize the downstream effects of somatic mutations recurrent in liver tissue of patients with chronic liver disease. The data in this study will be generated by spatial transcriptomic profiling of fresh frozen tissue using 10x Genomics VISIUM assay. The spatial gene expression data will be then matched to genomic and lipidomic data from adjacent tissue sections to infer genotype-phenotype associations.","abstract":"This study will aim to characterize the downstream effects of somatic mutations recurrent in liver tissue of patients with chronic liver disease. The data in this study will be generated by spatial transcriptomic profiling of fresh frozen tissue using 10x Genomics VISIUM assay. The spatial gene expression data will be then matched to genomic and lipidomic data from adjacent tissue sections to infer genotype-phenotype associations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005610","title":"WGBS and oxBS-seq for APL","description":null,"abstract":"Whole genome bisulfite sequencing (WGBS) data and oxidative bisulfite sequencing(oxBS-seq) data of an acute promyelocytic leukemia clinical specimen","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-18T01:12:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005611","title":"neuroblastoma_life_history","description":"The aim of this study is to understand the life history of neuroblastoma. We will compare multi-region sequencing of neuroblastoma tumour with normal adrenal and other tissues to reconstruct the tumour phylogeny. We currently have one patient, but may be able to recruit 2-3 more.","abstract":"The aim of this study is to understand the life history of neuroblastoma. We will compare multi-region sequencing of neuroblastoma tumour with normal adrenal and other tissues to reconstruct the tumour phylogeny. We currently have one patient, but may be able to recruit 2-3 more.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005612","title":"Transcriptomic consequences of complex rearrangements inv8p23.1 and inv17q21.31 associated with Autism Spectrum Disorders","description":"We have performed an RNAseq analysis in order to elucidate the transcriptomic consequences of two complex rearrangements associated with Autism Spectrum Disorder, including patients and controls (total n=24).","abstract":"We have performed an RNAseq analysis in order to elucidate the transcriptomic consequences of two complex rearrangements associated with Autism Spectrum Disorder, including patients and controls (total n=24).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-20T17:00:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005613","title":"APL Oxford Nanopore sequencing - nanome","description":null,"abstract":"DNA methylation-calling tools for Oxford Nanopore sequencing: a survey and human epigenome-wide evaluation\nBackground: Nanopore long-read sequencing technology greatly expands the capacity of long-range, single-molecule DNA-modification detection. A growing number of analytical tools have been developed to detect DNA methylation from nanopore sequencing reads. Here, we assess the performance of different methylation-calling tools to provide a systematic evaluation to guide researchers performing human epigenome-wide studies.\n\nResults:  We compare seven analytic tools for detecting DNA methylation from nanopore long-read sequencing data generated from human natural DNA at a whole genome scale. We evaluate the per-read and per-site performance of CpG methylation prediction across different genomic contexts, CpG site coverage, and computational resources consumed by each tool. The seven tools exhibit different performances across the evaluation criteria. We show that the methylation prediction at regions with discordant DNA methylation patterns, intergenic regions, low CG density regions, and repetitive regions show room for improvement across all tools. Furthermore, we demonstrate that 5hmC levels at least partly contribute to the discrepancy between bisulfite and nanopore sequencing. Lastly, we provide an online DNA methylation database ( https://nanome.jax.org ) to display the DNA methylation levels detected by nanopore sequencing and bisulfite sequencing data across different genomic contexts.\n\nConclusions: Our study is the first systematic benchmark of computational methods for detection of mammalian whole-genome DNA-modifications in nanopore sequencing. We provide a broad foundation for cross-platform standardization and an evaluation of analytical tools designed for genome-scale modified-base detection using nanopore sequencing.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-20T21:10:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005614","title":"Clonal dynamics of BRAF-driven drug resistance in EGFR-mutant lung cancer","description":null,"abstract":"Activation of MAPK signaling via BRAF mutations may limit the activity of EGFR inhibitors in EGFR-mutant lung cancer patients. However, the impact of BRAF mutations on the selection and fitness of resistant, EGFR-mutant clones during anti-EGFR therapy remains elusive. We tracked the emergence of subclonal mutations by whole-exome sequencing and performed clonal analyses of individual metastases during therapy. Complementary functional analyses of polyclonal EGFR-mutant cell pools showed a dose-dependent enrichment of BRAFV600E and a loss of EGFR inhibitor susceptibility. The emerging clones remain stable and become vulnerable to combined EGFR, RAF and MEK inhibition. Moreover, only osimertinib/trametinib combination treatment, but not monotherapy with either of these drugs, leads to a robust tumor shrinkage in EGFR-driven xenograft models harboring BRAFV600E mutations. These data provide novel insights into the dynamics of clonal evolution of EGFR-mutant tumors and the therapeutic implications of BRAF co-mutations that may facilitate the development of treatment strategies to improve the prognosis of these patients.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005615","title":"Pediatric B-cell precursor acute lymphoblastic leukemia samples with very early relapse","description":"In this study we performed a genomic analysis of diagnosis-relapse pairs of 12 children who relapsed very early, followed by a deep-sequencing validation of all identified mutations. In addition, we included one case with a good initial treatment response and on-treatment relapse at the end of upfront therapy.","abstract":"In this study we performed a genomic analysis of diagnosis-relapse pairs of 12 children who relapsed very early, followed by a deep-sequencing validation of all identified mutations. In addition, we included one case with a good initial treatment response and on-treatment relapse at the end of upfront therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-21T10:50:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005616","title":"Combined Metabolic Activators Reduces Liver Fat in Nonalcoholic Fatty Liver Disease Patients","description":"Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMA) promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria and eventually removes excess fat from the liver. Here, we tested the safety and efficacy of CMA in NAFLD patients in a placebo-controlled 10-week study. We found that CMA significantly decreased hepatic steatosis and levels of aspartate aminotransferase, alanine aminotransferase, uric acid, and creatinine, whereas found no differences on these variables in the placebo group after adjustment for weight loss. By integrating clinical data with plasma metabolomics and inflammatory proteomics as well as oral and gut metagenomics data, we revealed the underlying molecular mechanisms associated with the reduced hepatic fat and inflammation in NAFLD patients and identified the key players involved in the host-microbiome interactions. In conclusion, we showed that CMA can be used to develop a pharmacological treatment strategy in NAFLD patients.","abstract":"Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMA) promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria and eventually removes excess fat from the liver. Here, we tested the safety and efficacy of CMA in NAFLD patients in a placebo-controlled 10-week study. We found that CMA significantly decreased hepatic steatosis and levels of aspartate aminotransferase, alanine aminotransferase, uric acid, and creatinine, whereas found no differences on these variables in the placebo group after adjustment for weight loss. By integrating clinical data with plasma metabolomics and inflammatory proteomics as well as oral and gut metagenomics data, we revealed the underlying molecular mechanisms associated with the reduced hepatic fat and inflammation in NAFLD patients and identified the key players involved in the host-microbiome interactions. In conclusion, we showed that CMA can be used to develop a pharmacological treatment strategy in NAFLD patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-21T11:07:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005617","title":"Genomic abnormalities of TP53 define distinct risk groups of paediatric B-cell non-Hodgkin lymphoma","description":"TP53 alterations are associated with adverse outcome in many malignancies; however, whilst common in paediatric B-NHL, their utility as a risk classifier in this setting is unknown. We evaluated the clinical significance of TP53 abnormalities (mutations, deletion and/or copy number neutral loss of heterozygosity) in a large UK paediatric B-NHL cohort (n=95) and determined their impact on survival.","abstract":"TP53 alterations are associated with adverse outcome in many malignancies; however, whilst common in paediatric B-NHL, their utility as a risk classifier in this setting is unknown. We evaluated the clinical significance of TP53 abnormalities (mutations, deletion and/or copy number neutral loss of heterozygosity) in a large UK paediatric B-NHL cohort (n=95) and determined their impact on survival.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-21T14:59:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005618","title":"APL nanopore sequencing","description":"Nanopore sequencing for an APL patient","abstract":"Nanopore sequencing for an APL patient","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-21T16:47:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005619","title":"IVF Whole genome prediction","description":"Preimplantation Genetic Testing (PGT) of in vitro fertilized (IVF) embryos has been proposed as a method to reduce transmission of common disease, although comprehensive genetic assessment remains unavailable. Here we use a combination of molecular and statistical techniques to reliably and accurately infer inherited genome sequence in 110 embryos. We combine polygenic risk scores (PRS) and rare variation to model susceptibility across 12 common conditions.","abstract":"Preimplantation Genetic Testing (PGT) of in vitro fertilized (IVF) embryos has been proposed as a method to reduce transmission of common disease, although comprehensive genetic assessment remains unavailable. Here we use a combination of molecular and statistical techniques to reliably and accurately infer inherited genome sequence in 110 embryos. We combine polygenic risk scores (PRS) and rare variation to model susceptibility across 12 common conditions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-21T17:23:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005620","title":"Multifocal ileal NETs study WGS normal tissue","description":null,"abstract":"Ileal neuroendocrine tumors (NETs) represent the most common neoplasm of the small intestine. Although up to 50% of patients with ileal NETs are diagnosed with multifocal disease, the mechanisms by which multifocal ileal NETs arise are not yet understood. In this study, we analyzed genome-wide sequencing data to examine patterns of copy number variation in 40 synchronous primary ileal NETs derived from three patients. Chromosome (chr) 18 loss of heterozygosity (LOH) was the most frequent copy number alteration identified; however, not all primary tumors from the same patient had evidence of this LOH. Our data revealed three distinct patterns of chr18 allelic loss, indicating that primary tumors from the same patient can present different LOH patterns including retention of either parental allele. In conclusion, our results are consistent with the model that multifocal ileal NETs originate independently. In addition, they suggest that there is no specific germline allele on chr18 that is the target of somatic LOH.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-22T03:36:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005621","title":"Multifocal ileal NETs study WGS HF3J5CCXY","description":null,"abstract":"Ileal neuroendocrine tumors (NETs) represent the most common neoplasm of the small intestine. Although up to 50% of patients with ileal NETs are diagnosed with multifocal disease, the mechanisms by which multifocal ileal NETs arise are not yet understood. In this study, we analyzed genome-wide sequencing data to examine patterns of copy number variation in 40 synchronous primary ileal NETs derived from three patients. Chromosome (chr) 18 loss of heterozygosity (LOH) was the most frequent copy number alteration identified; however, not all primary tumors from the same patient had evidence of this LOH. Our data revealed three distinct patterns of chr18 allelic loss, indicating that primary tumors from the same patient can present different LOH patterns including retention of either parental allele. In conclusion, our results are consistent with the model that multifocal ileal NETs originate independently. In addition, they suggest that there is no specific germline allele on chr18 that is the target of somatic LOH.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-22T03:50:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005622","title":"Multifocal ileal NETs study WGS HF3FKCCXY","description":null,"abstract":"Ileal neuroendocrine tumors (NETs) represent the most common neoplasm of the small intestine. Although up to 50% of patients with ileal NETs are diagnosed with multifocal disease, the mechanisms by which multifocal ileal NETs arise are not yet understood. In this study, we analyzed genome-wide sequencing data to examine patterns of copy number variation in 40 synchronous primary ileal NETs derived from three patients. Chromosome (chr) 18 loss of heterozygosity (LOH) was the most frequent copy number alteration identified; however, not all primary tumors from the same patient had evidence of this LOH. Our data revealed three distinct patterns of chr18 allelic loss, indicating that primary tumors from the same patient can present different LOH patterns including retention of either parental allele. In conclusion, our results are consistent with the model that multifocal ileal NETs originate independently. In addition, they suggest that there is no specific germline allele on chr18 that is the target of somatic LOH.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-22T15:02:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005623","title":"Multifocal ileal NETs study WGS HFG3FCCXY","description":null,"abstract":"Ileal neuroendocrine tumors (NETs) represent the most common neoplasm of the small intestine. Although up to 50% of patients with ileal NETs are diagnosed with multifocal disease, the mechanisms by which multifocal ileal NETs arise are not yet understood. In this study, we analyzed genome-wide sequencing data to examine patterns of copy number variation in 40 synchronous primary ileal NETs derived from three patients. Chromosome (chr) 18 loss of heterozygosity (LOH) was the most frequent copy number alteration identified; however, not all primary tumors from the same patient had evidence of this LOH. Our data revealed three distinct patterns of chr18 allelic loss, indicating that primary tumors from the same patient can present different LOH patterns including retention of either parental allele. In conclusion, our results are consistent with the model that multifocal ileal NETs originate independently. In addition, they suggest that there is no specific germline allele on chr18 that is the target of somatic LOH.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-22T15:12:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005624","title":"Multifocal ileal NETs study WGS HF3NYCCXY","description":null,"abstract":"Ileal neuroendocrine tumors (NETs) represent the most common neoplasm of the small intestine. Although up to 50% of patients with ileal NETs are diagnosed with multifocal disease, the mechanisms by which multifocal ileal NETs arise are not yet understood. In this study, we analyzed genome-wide sequencing data to examine patterns of copy number variation in 40 synchronous primary ileal NETs derived from three patients. Chromosome (chr) 18 loss of heterozygosity (LOH) was the most frequent copy number alteration identified; however, not all primary tumors from the same patient had evidence of this LOH. Our data revealed three distinct patterns of chr18 allelic loss, indicating that primary tumors from the same patient can present different LOH patterns including retention of either parental allele. In conclusion, our results are consistent with the model that multifocal ileal NETs originate independently. In addition, they suggest that there is no specific germline allele on chr18 that is the target of somatic LOH.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-22T15:16:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005625","title":"Multifocal ileal NETs study WGS HFFWLCCXY","description":null,"abstract":"Ileal neuroendocrine tumors (NETs) represent the most common neoplasm of the small intestine. Although up to 50% of patients with ileal NETs are diagnosed with multifocal disease, the mechanisms by which multifocal ileal NETs arise are not yet understood. In this study, we analyzed genome-wide sequencing data to examine patterns of copy number variation in 40 synchronous primary ileal NETs derived from three patients. Chromosome (chr) 18 loss of heterozygosity (LOH) was the most frequent copy number alteration identified; however, not all primary tumors from the same patient had evidence of this LOH. Our data revealed three distinct patterns of chr18 allelic loss, indicating that primary tumors from the same patient can present different LOH patterns including retention of either parental allele. In conclusion, our results are consistent with the model that multifocal ileal NETs originate independently. In addition, they suggest that there is no specific germline allele on chr18 that is the target of somatic LOH.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-22T15:35:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005626","title":"Matched tissue from BRCA1/2 mutation carriers and confirmed non-BRCA mutation carriers","description":"Methylation data from individuals with BRCA1/2 mutation and controls from cervical, buccal, and blood samples.","abstract":"Methylation data from individuals with BRCA1/2 mutation and controls from cervical, buccal, and blood samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-23T12:49:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005627","title":"A microRNA-signature that correlates with cognition and is a target against cognitive decline","description":"While some individuals age without pathological memory impairments, others develop age-associated cognitive diseases. Since changes in cognitive function develop slowly over time in these patients, they are often diagnosed at an advanced stage of molecular pathology, a time point when causative treatments fail. Thus, there is great need for the identification of inexpensive and minimal invasive approaches that could be used for screening with the aim to to identify individuals at risk for cognitive decline that can then undergo further diagnostics and eventually stratified therapies. In this study we use an integrative approach combining the analysis of human data and mechanistic studies in model systems to identify a circulating 3-microRNA signature that reflect key processes linked to neural homeostasis and informs about cognitive status. We furthermore provide evidence that expression changes of this signature represent multiple mechanisms de-regulated in the aging and diseased brain and are a suitable target for RNA therapeutics.","abstract":"While some individuals age without pathological memory impairments, others develop age-associated cognitive diseases. Since changes in cognitive function develop slowly over time in these patients, they are often diagnosed at an advanced stage of molecular pathology, a time point when causative treatments fail. Thus, there is great need for the identification of inexpensive and minimal invasive approaches that could be used for screening with the aim to to identify individuals at risk for cognitive decline that can then undergo further diagnostics and eventually stratified therapies. In this study we use an integrative approach combining the analysis of human data and mechanistic studies in model systems to identify a circulating 3-microRNA signature that reflect key processes linked to neural homeostasis and informs about cognitive status. We furthermore provide evidence that expression changes of this signature represent multiple mechanisms de-regulated in the aging and diseased brain and are a suitable target for RNA therapeutics.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-23T16:56:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005628","title":"Mucosal_Organoid_Pilot","description":"A feasibility study to build a genotyped mucosal organoid biobank or patients enrolled in our current studies for scRNAseq of intestine/blood 1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Pilot data will be used to support application for funds to create the bank and perform HTP target validation of our primary biopsy work, through eQTL screening. We plan to extend the bank by up to 3000 organoids in the next QQ if the project is successful. The bank will also facilitate cheaper, faster genotype-specific target validation (compared with variant-edited iPSC differentiated to intestine), as well as genetic screens and functional studies in the next QQ.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005629","title":"Whole genome sequencing data for 10 hepatocellular carcinomas (HCC) and matched non-tumor liver tissues + optical mapping data for 4 HCC and 3 matched non-tumor liver tissues.","description":"Oncogene activation leads to replication stress and promotes genomic instability. Here we combine optical mapping and whole genome sequencing to explore in-depth the nature of structural variants (SVs) induced by replication stress in cyclin-activated hepatocellular carcinomas (CCN-HCC). In addition to classical tandem duplications, CCN-HCC display frequent intra- and inter-chromosomal templated insertion cycles (TIC) likely resulting from template switching events. Template switching preferentially involves active topologically associated domains that are close in the 3D genome organization. Template sizes depend on the type of cyclin activation and are coordinated within each TIC. Replication stress induces continuous accumulation of SVs during CCN-HCC progression, fostering the acquisition of new driver alterations and large-scale copy-number changes at TIC borders. Together, this analysis sheds light on the mechanisms, dynamics and consequences of SV accumulation in tumors with oncogene-induced replication stress.","abstract":"Oncogene activation leads to replication stress and promotes genomic instability. Here we combine optical mapping and whole genome sequencing to explore in-depth the nature of structural variants (SVs) induced by replication stress in cyclin-activated hepatocellular carcinomas (CCN-HCC). In addition to classical tandem duplications, CCN-HCC display frequent intra- and inter-chromosomal templated insertion cycles (TIC) likely resulting from template switching events. Template switching preferentially involves active topologically associated domains that are close in the 3D genome organization. Template sizes depend on the type of cyclin activation and are coordinated within each TIC. Replication stress induces continuous accumulation of SVs during CCN-HCC progression, fostering the acquisition of new driver alterations and large-scale copy-number changes at TIC borders. Together, this analysis sheds light on the mechanisms, dynamics and consequences of SV accumulation in tumors with oncogene-induced replication stress.","study_type":"Other","pubmed_ids":[35395067],"external_links":null,"is_released":true,"released_date":"2021-09-24T10:45:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005630","title":"Standardisation of Single-Cell RNA-seq Protocols for Tumors (START)","description":null,"abstract":"Cancer can arise in almost any tissue in the human body. Single-cell analysis in cancer may yield insights into the functioning and development of human cells and tissues both in health and disease, and can therefore contribute to laying the foundations for the Human Cell Atlas (HCA). As each tumor type arises in different tissues, one major hurdle, shared with the HCA, is to develop protocols and SOPs for preparation and preservation, sample handling, and cell dissociation approaches for single-cell profiling for a variety of clinical samples. Another challenge is to develop systematic pipelines for sample procurement, profiling and analysis. In collaboration with 5 international institutes, we will provide standardization and best practices recommendations for single-cell and single-nucleus RNA-sequencing of normal and cancer cells in clinical tumor samples. We will test and optimize each processing step both within the same laboratory and across labs for reproducibility. We will share expertise and select protocols that provide optimal representation of both tumor and normal breast tissues. We will apply strict benchmarks and ensure that the resulting datasets comply with the HCA data ingest infrastructure. Our project will help develop robust protocols for tissue preparation and for the creation of pipelines for direct profiling of clinical samples that may prove essential for the entire HCA community.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005631","title":"Genomic drivers of large B-cell lymphoma resistance to CD19 CAR-T therapy","description":null,"abstract":"DLBCL tumor biopsies (with paired germline samples) of 31 patients treated with axi-cel were analyzed by WGS. Sequencing libraries were prepared using the TruSeq DNA PCR-free HT sample preparation kit from Illumina. Libraries were sequenced on a S4-300 flow cell on the NovaSeq 6000. Paired-end 150bp reads were generated to yield an average depth of 30x per sample. FASTQ files were generated using the Illumina BCL2FASTQ algorithm and used for downstream processing. Tumor and normal paired samples were aligned against the GRCh38 genome build.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005632","title":"Genomic Signatures Define Three Subtypes of EGFR-Mutant Stage II-III NSCLC With Distinct Adjuvant Therapy Outcomes","description":null,"abstract":"The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival (DFS) of resected EGFR-mutant stage II-IIIA non-small cell lung cancer (NSCLC). However, not all patients experienced favorable clinical outcomes with TKI, raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-28T10:22:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005633","title":"scRNAseq of human primary nasal epithelium differentiated at air-liquid interface exposed to SARS-CoV2","description":"The nasal epithelium is a plausible entry point for SARS-CoV-2, a site of pathogenesis and transmission, and may initiate the host response to SARS-CoV-2. Antiviral interferon responses are critical to outcome of SARS-CoV-2. Yet little is known about the interaction between SARS-CoV-2 and innate immunity in this tissue. Here we applied single-cell RNA sequencing and proteomics to a primary cell model of human primary nasal epithelium differentiated at air-liquid interface.","abstract":"The nasal epithelium is a plausible entry point for SARS-CoV-2, a site of pathogenesis and transmission, and may initiate the host response to SARS-CoV-2. Antiviral interferon responses are critical to outcome of SARS-CoV-2. Yet little is known about the interaction between SARS-CoV-2 and innate immunity in this tissue. Here we applied single-cell RNA sequencing and proteomics to a primary cell model of human primary nasal epithelium differentiated at air-liquid interface.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-28T16:09:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005634","title":"Single-cell RNA-seq of bronchoalveolar lavage (BAL) fluid of late stage severe COVID-19 patients","description":"COVID-19-induced ‘acute respiratory distress syndrome’ (ARDS) is associated with prolonged respiratory failure and high mortality, but the mechanistic basis of lung injury remains incompletely understood. Here, we analyzed pulmonary immune responses and lung pathology in two cohorts of patients with COVID-19 ARDS using functional single cell genomics, immunohistology and electron microscopy. We describe an accumulation of CD163-expressing monocyte-derived macrophages, that acquired a profibrotic transcriptional phenotype during COVID-19 ARDS. Gene set enrichment and computational data integration revealed a significant similarity between COVID-19-associated macrophages and profibrotic macrophage populations identified in idiopathic pulmonary fibrosis. COVID-19 ARDS was associated with clinical, radiographic, histopathological, and ultrastructural hallmarks of pulmonary fibrosis. Exposure of human monocytes to SARS-CoV-2, but not Influenza A virus or viral RNA analogs, was sufficient to induce a similar profibrotic phenotype in vitro. In conclusion, we demonstrate that SARS-CoV-2 triggers profibrotic macrophage responses and pronounced fibroproliferative ARDS.","abstract":"COVID-19-induced ‘acute respiratory distress syndrome’ (ARDS) is associated with prolonged respiratory failure and high mortality, but the mechanistic basis of lung injury remains incompletely understood. Here, we analyzed pulmonary immune responses and lung pathology in two cohorts of patients with COVID-19 ARDS using functional single cell genomics, immunohistology and electron microscopy. We describe an accumulation of CD163-expressing monocyte-derived macrophages, that acquired a profibrotic transcriptional phenotype during COVID-19 ARDS. Gene set enrichment and computational data integration revealed a significant similarity between COVID-19-associated macrophages and profibrotic macrophage populations identified in idiopathic pulmonary fibrosis. COVID-19 ARDS was associated with clinical, radiographic, histopathological, and ultrastructural hallmarks of pulmonary fibrosis. Exposure of human monocytes to SARS-CoV-2, but not Influenza A virus or viral RNA analogs, was sufficient to induce a similar profibrotic phenotype in vitro. In conclusion, we demonstrate that SARS-CoV-2 triggers profibrotic macrophage responses and pronounced fibroproliferative ARDS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-29T08:41:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005635","title":"lorem ipsum","description":null,"abstract":"mock to see the minimum required to get an accession","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005636","title":"Immune infiltrate and tumor microenvironment transcriptional programs stratify pediatric osteosarcoma into prognostic groups at diagnosis","description":null,"abstract":"Outcomes for adolescents/young adults with osteosarcoma has not improved since decades. Chaotic karyotype of this rare tumor has precluded identification of prognostic biomarkers/stratification. We reasoned that transcriptomic study should overcome this genetic complexity. From the RNA-sequencing of 79 osteosarcomas diagnostic biopsies, we identified stable independent components (Metagenes) recapitulating the tumor microenvironment and clones. Metagene unsupervised classification stratified this cohort into good (G1) and poor (G2) prognostic tumors on overall survival. Multivariate survival analysis ranked this stratification as the most influential variable. Functional characterization associates G1 tumors with innate immunity and G2 tumors with angiogenic, osteoclastic and adipogenic activities as well as PPAR pathway upregulation. We next defined a short gene signature to predict G1/G2 tumors from RNA-seq validated within independent cohort of 82 osteosarcomas. We further validated the signature by custom Nanostring panel in 96 additional osteosarcomas. Our study thus proposes new biomarkers to detect hard-to-treat patients as well as related new therapeutic options.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005637","title":"ADAPTeR Study: RNAseq data from ccRCC patients","description":"RNAseq from tumour, mets, and PEACE study","abstract":"RNAseq from tumour, mets, and PEACE study","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-30T17:35:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005638","title":"ADAPTeR Study: WES data from ccRCC patients","description":"ADAPTeR study RNAseq from multi-region samples taken pre and post nivolumab.","abstract":"ADAPTeR study RNAseq from multi-region samples taken pre and post nivolumab.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-30T17:53:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005639","title":"ADAPTeR Study: TCRseq data from ccRCC patients","description":"TCRseq from ccRCC patient","abstract":"TCRseq from ccRCC patient","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-30T18:09:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005640","title":"ADAPTeR Study: scRNA and scTCR data from TILs from two ccRCC patients treated with anti-PD1","description":"TILs were extracted from two ccRCC patients treated with (Nivolumab) anti-PD1, one was responsive to treatment, the other non-responsive. IgG4 staining was used to separate cells into anti-PD1 bound and unbound, the samples then underwent paired scRNA and scTCR sequencing on the 10x Genomics platform.","abstract":"TILs were extracted from two ccRCC patients treated with (Nivolumab) anti-PD1, one was responsive to treatment, the other non-responsive. IgG4 staining was used to separate cells into anti-PD1 bound and unbound, the samples then underwent paired scRNA and scTCR sequencing on the 10x Genomics platform.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-09-30T19:19:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005641","title":"Proteom characterization in primary colorectal cancer and corresponding liver metastasis","description":"Colorectal adenocarcinomas (CRC) are one of the most commonly diagnosed tumors worldwide. Colorectal adenocarcinomas primarily metastasize into the liver and (less often) into the peritoneum. Patients suffering from CRC-liver metastasis (CRC-LM) typically present with a dismal overall survival compared to non-metastasized CRC patients. The metastasis process and metastasis promoting factors in patients with CRC are under intensive debate. However, CRC studies investigating the proteome biology are lacking. Formalin-fixed paraffin-embedded (FFPE) tissue specimens provide a valuable resource for comprehensive proteomic studies of a broad variety of clinical malignancies. The presented pilot study compares the proteome of primary CRC and patient-matched CRC-LM. The applied protocol allows a reproducible and straightforward identification and quantification of over 2,600 proteins within the dissected tumorous tissue. Subsequent unsupervised clustering reveals distinct proteome biologies of the primary CRC and the corresponding CRC-LM. Statistical analysis yields multiple differentially abundant proteins in either primary CRC or their corresponding liver metastases. A more detailed analysis of dysregulated biological processes suggests an active immune response in the liver metastases, including several proteins of the complement system. Proteins with structural roles, e.g. cytoskeleton organization or cell junction assembly appear to be less prominent in liver metastases as compared to primary CRC. Immunohistochemistry corroborates proteomic high expression levels of metabolic proteins in CRC-LM. We further assessed how the in vitro inhibition of two in CRC-LM enriched metabolic proteins affected cell proliferation and chemosensitivity. The presented proteomic investigation in a small clinical cohort promotes a more comprehensive understanding of the distinct proteome biology of primary CRC and their corresponding liver metastases.","abstract":"Colorectal adenocarcinomas (CRC) are one of the most commonly diagnosed tumors worldwide. Colorectal adenocarcinomas primarily metastasize into the liver and (less often) into the peritoneum. Patients suffering from CRC-liver metastasis (CRC-LM) typically present with a dismal overall survival compared to non-metastasized CRC patients. The metastasis process and metastasis promoting factors in patients with CRC are under intensive debate. However, CRC studies investigating the proteome biology are lacking. Formalin-fixed paraffin-embedded (FFPE) tissue specimens provide a valuable resource for comprehensive proteomic studies of a broad variety of clinical malignancies. The presented pilot study compares the proteome of primary CRC and patient-matched CRC-LM. The applied protocol allows a reproducible and straightforward identification and quantification of over 2,600 proteins within the dissected tumorous tissue. Subsequent unsupervised clustering reveals distinct proteome biologies of the primary CRC and the corresponding CRC-LM. Statistical analysis yields multiple differentially abundant proteins in either primary CRC or their corresponding liver metastases. A more detailed analysis of dysregulated biological processes suggests an active immune response in the liver metastases, including several proteins of the complement system. Proteins with structural roles, e.g. cytoskeleton organization or cell junction assembly appear to be less prominent in liver metastases as compared to primary CRC. Immunohistochemistry corroborates proteomic high expression levels of metabolic proteins in CRC-LM. We further assessed how the in vitro inhibition of two in CRC-LM enriched metabolic proteins affected cell proliferation and chemosensitivity. The presented proteomic investigation in a small clinical cohort promotes a more comprehensive understanding of the distinct proteome biology of primary CRC and their corresponding liver metastases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-01T10:27:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005642","title":"Paediatric_CNS_tumour_autopsy_DNA_WES","description":"Paediatric gliomas likely have their origins in embryogenesis. This WES extension to the WGS study seeks to estimate the occurrence of driver mutations within the normal tissues of patients which have developed lethal brain tumours and compare the incidence between those that have a germline predisposition and those that don't.","abstract":"Paediatric gliomas likely have their origins in embryogenesis. This WES extension to the WGS study seeks to estimate the occurrence of driver mutations within the normal tissues of patients which have developed lethal brain tumours and compare the incidence between those that have a germline predisposition and those that don't.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-01T10:56:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005643","title":"ADAPTeR Study: TCRseq data from ccRCC patients","description":null,"abstract":"TCRseq from ccRCC patients","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005644","title":"ADAPTeR Study: scRNA and scTCR data from TILs from two ccRCC patients treated with anti-PD1","description":null,"abstract":"TILs were extracted from two ccRCC patients treated with (Nivolumab) anti-PD1, one was responsive to treatment, the other non-responsive. IgG4 staining was used to separate cells into anti-PD1 bound and unbound, the samples then underwent paired scRNA and scTCR sequencing on the 10x Genomics platform.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005645","title":"ADAPTeR Study: RNAseq data from ccRCC patients","description":null,"abstract":"RNAseq from tumours, mets, and peace study","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005646","title":"ADAPTeR Study: WES data from ccRCC patients","description":null,"abstract":"WES data from ccRCC patients","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005647","title":"Multi-omic Profiling of Central Nervous System Leukemia Identifies mRNA Translation as a Therapeutic Target","description":"Central nervous system (CNS) dissemination of B-precursor acute lymphoblastic leukemia (B-ALL) has poor prognosis and remains a therapeutic challenge. Here we performed targeted DNA sequencing, transcriptional and proteomic profiling of paired leukemia infiltrating cells in the bone marrow (BM) and CNS of xenografts. Genes governing mRNA translation were upregulated in CNS leukemia, and subclonal genetic profiling confirmed this in both BM-concordant and BM-discordant CNS mutational populations.  CNS leukemia cells were exquisitely sensitive to the translation inhibitor omacetaxine mepesuccinate, which reduced xenograft leptomeningeal disease burden. Proteomics demonstrated greater abundance of secreted proteins in CNS infiltrating cells including complement component 3 (C3) and drug targeting of C3 influenced CNS disease in xenografts. CNS infiltrating cells also exhibited selection for stemness traits and metabolic reprogramming. Overall, our study identifies therapeutic targeting of mRNA translation as a novel therapeutic approach for B-ALL leptomeningeal disease.","abstract":"Central nervous system (CNS) dissemination of B-precursor acute lymphoblastic leukemia (B-ALL) has poor prognosis and remains a therapeutic challenge. Here we performed targeted DNA sequencing, transcriptional and proteomic profiling of paired leukemia infiltrating cells in the bone marrow (BM) and CNS of xenografts. Genes governing mRNA translation were upregulated in CNS leukemia, and subclonal genetic profiling confirmed this in both BM-concordant and BM-discordant CNS mutational populations.  CNS leukemia cells were exquisitely sensitive to the translation inhibitor omacetaxine mepesuccinate, which reduced xenograft leptomeningeal disease burden. Proteomics demonstrated greater abundance of secreted proteins in CNS infiltrating cells including complement component 3 (C3) and drug targeting of C3 influenced CNS disease in xenografts. CNS infiltrating cells also exhibited selection for stemness traits and metabolic reprogramming. Overall, our study identifies therapeutic targeting of mRNA translation as a novel therapeutic approach for B-ALL leptomeningeal disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-01T19:46:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005648","title":"The genomic landscape of serrated lesion of the colorectum","description":"Serrated lesions of the colorectum are the precursors of 15-30% of colorectal cancers (CRCs). These lesions have a peculiar morphological appearance, and they are more difficult to detect than conventional adenomatous polyps. In this study we sought to define the genomic landscape of these lesions using high depth targeted sequencing.","abstract":"Serrated lesions of the colorectum are the precursors of 15-30% of colorectal cancers (CRCs). These lesions have a peculiar morphological appearance, and they are more difficult to detect than conventional adenomatous polyps. In this study we sought to define the genomic landscape of these lesions using high depth targeted sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-04T09:57:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005649","title":"Variation and transmission of the human gut microbiota across generations - shotgun data","description":"Although composition and functional potential of the human gut microbiota evolve over lifespan, kinship has been identified as a key covariate of microbial community diversification. To date, sharing of microbiota features within families has however mostly been assessed between parents and their direct offspring. Here, we investigate potential transmission and persistence of familial microbiome patterns and microbial genotypes in a family cohort (N=102) spanning three to five generations over the same female bloodline. We observe microbiome community composition to be associated with kinship, with seven (low-abundant) genera displaying familial distribution patterns. While kinship and current cohabitation emerged as closely entangled variables, our explorative analyses of microbial genotype distribution and transmission estimates point at the latter as a key covariate of strain dissemination. Highest potential transmission rates are estimated between sisters and mother-daughter pairs, decreasing with increasing daughter’s age, and being higher among cohabiting pairs than those living apart. Although rare, we do detect potential transmission events spanning three and four generations, primarily involving species of the genera Alistipes and Bacteroides. Overall, while our analyses confirm the existence of family-bound microbiome community profiles, transmission or co-acquisition of bacterial strains appears to be strongly linked to cohabitation.","abstract":"Although composition and functional potential of the human gut microbiota evolve over lifespan, kinship has been identified as a key covariate of microbial community diversification. To date, sharing of microbiota features within families has however mostly been assessed between parents and their direct offspring. Here, we investigate potential transmission and persistence of familial microbiome patterns and microbial genotypes in a family cohort (N=102) spanning three to five generations over the same female bloodline. We observe microbiome community composition to be associated with kinship, with seven (low-abundant) genera displaying familial distribution patterns. While kinship and current cohabitation emerged as closely entangled variables, our explorative analyses of microbial genotype distribution and transmission estimates point at the latter as a key covariate of strain dissemination. Highest potential transmission rates are estimated between sisters and mother-daughter pairs, decreasing with increasing daughter’s age, and being higher among cohabiting pairs than those living apart. Although rare, we do detect potential transmission events spanning three and four generations, primarily involving species of the genera Alistipes and Bacteroides. Overall, while our analyses confirm the existence of family-bound microbiome community profiles, transmission or co-acquisition of bacterial strains appears to be strongly linked to cohabitation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-04T10:17:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005650","title":"Longitudinal_Cambridge_study_COVID19_TACTIC","description":"Investigating tissue immune responses to COVID-19 in live and deceased donors","abstract":"SARSCoV-2 is a novel coronavirus responsible for the current global pandemic, with more than 980,000 cases confirmed worldwide (WHO Situational Report 73, April 2nd 2020). The clinical course of SARSCoV-2 is variable, ranging from asymptomatic disease to acute respiratory distress syndrome (ARDS) requiring ventilatory support. Detailed interrogation of the immune response has largely \nfocused on studying peripheral blood, for example (Thevarajan et al. Nat Med 2020, epub). However, in-depth analyses of tissue immune responses to SARSCoV-2, particularly in severe disease, are limited. Notably, the hyperinflammatory phase of the disease tends to occur more than a week after initial symptoms, which may correspond to either an inefficient adaptive immune response, or in contrast, antibodydependent enhancement. Older individuals are more susceptible to the virus, with variable outcomes in this age group and a mortality rate of up to 30%, but the immunological factors underpinning this variability are not understood. Of note, it is well-described that ageing is associated with more exuberant myeloid cell responses and a state of chronic, low-grade, systemic inflammation with variable exhaustion in the lymphoid compartment. This study has three aims: 1. To characterise the local immune response to SARSCoV-2 in the respiratory tract in patients with severe, life-threatening disease. 2. To assess longitudinal systemic immune responses to SARSCoV-2 in severe disease, and to determine whether these reflect local immune responses. 3. To compare immune responses to SARSCoV-2 between the young and old. This research will include genetic and genomic analysis, including transcriptomics.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005651","title":"Variation and transmission of the human gut microbiota across generations - 16S data","description":"Although composition and functional potential of the human gut microbiota evolve over lifespan, kinship has been identified as a key covariate of microbial community diversification. To date, sharing of microbiota features within families has however mostly been assessed between parents and their direct offspring. Here, we investigate potential transmission and persistence of familial microbiome patterns and microbial genotypes in a family cohort (N=102) spanning three to five generations over the same female bloodline. We observe microbiome community composition to be associated with kinship, with seven (low-abundant) genera displaying familial distribution patterns. While kinship and current cohabitation emerged as closely entangled variables, our explorative analyses of microbial genotype distribution and transmission estimates point at the latter as a key covariate of strain dissemination. Highest potential transmission rates are estimated between sisters and mother-daughter pairs, decreasing with increasing daughter’s age, and being higher among cohabiting pairs than those living apart. Although rare, we do detect potential transmission events spanning three and four generations, primarily involving species of the genera Alistipes and Bacteroides. Overall, while our analyses confirm the existence of family-bound microbiome community profiles, transmission or co-acquisition of bacterial strains appears to be strongly linked to cohabitation.","abstract":"Although composition and functional potential of the human gut microbiota evolve over lifespan, kinship has been identified as a key covariate of microbial community diversification. To date, sharing of microbiota features within families has however mostly been assessed between parents and their direct offspring. Here, we investigate potential transmission and persistence of familial microbiome patterns and microbial genotypes in a family cohort (N=102) spanning three to five generations over the same female bloodline. We observe microbiome community composition to be associated with kinship, with seven (low-abundant) genera displaying familial distribution patterns. While kinship and current cohabitation emerged as closely entangled variables, our explorative analyses of microbial genotype distribution and transmission estimates point at the latter as a key covariate of strain dissemination. Highest potential transmission rates are estimated between sisters and mother-daughter pairs, decreasing with increasing daughter’s age, and being higher among cohabiting pairs than those living apart. Although rare, we do detect potential transmission events spanning three and four generations, primarily involving species of the genera Alistipes and Bacteroides. Overall, while our analyses confirm the existence of family-bound microbiome community profiles, transmission or co-acquisition of bacterial strains appears to be strongly linked to cohabitation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-04T13:54:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005652","title":"Perturbed NK Cell Homeostasis in Neutropenia","description":"Neutrophils have been suggested to play a critical role in terminal differentiation of NK cells. Whether this is a direct effect or a consequence of global immune changes with effects on NK cell homeostasis remains unknown. Here, we used high-resolution flow- and mass cytometry to examine NK cell repertoires in 64 patients with neutropenia and 27 healthy age- and gender-matched donors. A subgroup of patients with chronic neutropenia showed severely disrupted NK cell homeostasis manifested as increased frequencies of CD56bright NK cells and a lack of mature CD56dim NK cells. These immature NK cell repertoires were characterized by expression of proliferation/exhaustion markers Ki-67, Tim-3 and TIGIT and displayed blunted tumor target cell responses. Systems-level immune mapping revealed that the changes in immunophenotypes were confined to NK cells, leaving T cell differentiation intact. RNA sequencing of NK cells from these patients showed upregulation of a network of genes, including TNFSF9, CENPF, MKI67 and TOP2A, associated with apoptosis and the cell cycle, different from conventional CD56bright signatures. Profiling of 249 plasma proteins showed a coordinated enrichment of pathways related to apoptosis and cell turnover, which correlated with immature NK cell repertoires. Notably, most of these patients exhibited severe-grade neutropenia, suggesting that the profoundly altered NK cell homeostasis was connected to the severity of their underlying etiology. Hence, although our data suggests that neutrophils are dispensable for NK cell development and differentiation, some patients displayed a specific gap in the NK repertoire, associated with poor cytotoxic function and more severe disease manifestations.","abstract":"Neutrophils have been suggested to play a critical role in terminal differentiation of NK cells. Whether this is a direct effect or a consequence of global immune changes with effects on NK cell homeostasis remains unknown. Here, we used high-resolution flow- and mass cytometry to examine NK cell repertoires in 64 patients with neutropenia and 27 healthy age- and gender-matched donors. A subgroup of patients with chronic neutropenia showed severely disrupted NK cell homeostasis manifested as increased frequencies of CD56bright NK cells and a lack of mature CD56dim NK cells. These immature NK cell repertoires were characterized by expression of proliferation/exhaustion markers Ki-67, Tim-3 and TIGIT and displayed blunted tumor target cell responses. Systems-level immune mapping revealed that the changes in immunophenotypes were confined to NK cells, leaving T cell differentiation intact. RNA sequencing of NK cells from these patients showed upregulation of a network of genes, including TNFSF9, CENPF, MKI67 and TOP2A, associated with apoptosis and the cell cycle, different from conventional CD56bright signatures. Profiling of 249 plasma proteins showed a coordinated enrichment of pathways related to apoptosis and cell turnover, which correlated with immature NK cell repertoires. Notably, most of these patients exhibited severe-grade neutropenia, suggesting that the profoundly altered NK cell homeostasis was connected to the severity of their underlying etiology. Hence, although our data suggests that neutrophils are dispensable for NK cell development and differentiation, some patients displayed a specific gap in the NK repertoire, associated with poor cytotoxic function and more severe disease manifestations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005653","title":"PIK3CA mutation in a case of CTNNB1 mutant sinonasal glomangiopericytoma","description":null,"abstract":"Glomangiopericytomas are rare, primary sinonasal tumors. The existing literature is mostly limited to reports describing the clinicopathologic characteristics of these tumors. Here we report the whole exome sequencing of a case, which revealed somatic mutations in CTNNB1 and PIK3CA, the former previously associated with this pathology but the latter not described. Concurrent dysregulation of Wnt/beta-catenin and PI3K/AKT/mTOR signaling, secondary to mutations in these two oncogenes may be amenable to targeted treatment with existing clinically approved drugs. Genomic characterization of glomangiopericytomas remains lacking. This study reports novel co-existence of PIK3CA and CTNNB1 mutations in a case of glomangiopericytoma that may offer insight into the pathogenesis and potential for targeted medical therapies of this rare tumor.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-04T15:14:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005654","title":"A polygenic risk score for multiple myeloma risk prediction","description":null,"abstract":"There are overwhelming epidemiologic evidences that risk of multiple myeloma (MM) has a solid genetic background. Genome-wide association studies (GWAS) have identified 23 risk loci that contribute to the genetic susceptibility of MM, but the individual penetrance of each SNP is low, with odds ratios (OR) per risk allele ranging from 1.11 to 1.38.A possible approach to improve usefulness of genetic risk markers is to combine the SNPs in a polygenic risk score (PRS) in order to have a better estimation of their cumulative effect on the risk of developing the disease. Using 2,361 MM cases and 1,415 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium, we computed a weighted and an unweighted PRS. We observed associations with MM risk with OR=3.27, 95%CI 2.33-4.57, p=4.86×10-12 for the highest vs. lowest quintile of the weighted score, and OR=2.99, 95%CI 2.14-4.18, p=1.58×10-10 for the highest vs. lowest quintile of the unweighted score. We found a convincing association of a PRS generated with 23 SNPs and risk of MM that could be considered a first step towards the use of genetics for risk stratification in the general population.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005655","title":"RNAseq in blood CD34+ cells","description":"The aim of the project was to perform expression quantitative trait locus (eQTL) analysis in blood CD34+ cells from random blood donors.","abstract":"The aim of the project was to perform expression quantitative trait locus (eQTL) analysis in blood CD34+ cells from random blood donors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-05T16:20:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005656","title":"Pre-neoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma","description":"Normal-cell counterparts of solid and myeloid tumors accumulate mutations years before disease onset; whether this occurs in B-lymphocytes prior to lymphoma remains uncertain. In this study, we sequenced multiple stages of the B-lineage in elderly individuals and patients with lymphoplasmacytic lymphoma, a singular disease for studying lymphomagenesis because of high-prevalence of mutated MYD88.","abstract":"Normal-cell counterparts of solid and myeloid tumors accumulate mutations years before disease onset; whether this occurs in B-lymphocytes prior to lymphoma remains uncertain. In this study, we sequenced multiple stages of the B-lineage in elderly individuals and patients with lymphoplasmacytic lymphoma, a singular disease for studying lymphomagenesis because of high-prevalence of mutated MYD88.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-06T09:45:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005657","title":"Spatial_Transcriptome_Analysis","description":"Using single-cell and spatial genomics methods to profile the in vivo and in vitro engineered bone marrow micro-environments","abstract":"During hematopoiesis, the bone marrow microenvironment triggers specific signalling in hematopoietic stem cells (HSCs), inducing their differentiation into multiple immune lineages. A main constraint in the field is the lack of human in vitro models to recapitulate this process and provide mechanistic insights into the early steps of immune cell differentiation. Here, we aim to generate the first artificial bone marrow microenvironment in a dish to mechanistically dissect how it shapes immune cell identity and function in humans. We will combine single-cell and spatial genomics methods to profile the in vivo and in vitro engineered models. This work has relevant translational opportunities for immunotherapy, regenerative medicine and the catalysation of chimeric antigen-immune cells (CAR-immune cells), opening up new avenues in hematopoiesis research.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005658","title":"HCA_Bone_Marrow_LEAP_project_RNA","description":"Using single-cell and spatial genomics methods to profile the in vivo and in vitro engineered bone marrow micro-environments","abstract":"During hematopoiesis, the bone marrow microenvironment triggers specific signalling in hematopoietic stem cells (HSCs), inducing their differentiation into multiple immune lineages. A main constraint in the field is the lack of human in vitro models to recapitulate this process and provide mechanistic insights into the early steps of immune cell differentiation. Here, we aim to generate the first artificial bone marrow microenvironment in a dish to mechanistically dissect how it shapes immune cell identity and function in humans. We will combine single-cell and spatial genomics methods to profile the in vivo and in vitro engineered models. This work has relevant translational opportunities for immunotherapy, regenerative medicine and the catalysation of chimeric antigen-immune cells (CAR-immune cells), opening up new avenues in hematopoiesis research.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005659","title":"Mutant_clone_mapping_in_normal_oesohagus_and_skin_2","description":"We will use targeted exome sequencing to examine normal appearing oesophageal epithelium and skin to determine the mutational burden.  DNA will be extracted from epithelia of a defined size and we will overlay positional information from the epithelial pieces to give clone maps over a wide area.  This will be done in both oesophageal epithelium and skin","abstract":"We will use targeted exome sequencing to examine normal appearing oesophageal epithelium and skin to determine the mutational burden.  DNA will be extracted from epithelia of a defined size and we will overlay positional information from the epithelial pieces to give clone maps over a wide area.  This will be done in both oesophageal epithelium and skin","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-06T13:30:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005660","title":"Mutant_clone_mapping_in_oesohagus_restricted_bait","description":"We aim to assess the burden of mutant clones  in normal human oesophagus from donors aged 65+.  We will do this for a small number of genes which we know to be under positive dN/dS selection.  This will allow us to assess the patient to patient variation in mutational burden as well as any changes in selection which may occur with age.","abstract":"We aim to assess the burden of mutant clones  in normal human oesophagus from donors aged 65+.  We will do this for a small number of genes which we know to be under positive dN/dS selection.  This will allow us to assess the patient to patient variation in mutational burden as well as any changes in selection which may occur with age.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-06T13:32:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005661","title":"Whole-exome sequencing of HCC patients undergoing sorafenib treatment","description":"Whole-exome sequencing of hepatocellular carcinomas at various stages of sorafenib treatment","abstract":"Whole-exome sequencing of hepatocellular carcinomas at various stages of sorafenib treatment","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-06T14:44:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005662","title":"RNA-sequencing of HCC patients undergoing sorafenib treatment","description":"RNA-sequencing of hepatocellular carcinomas at various stages of sorafenib treatment","abstract":"RNA-sequencing of hepatocellular carcinomas at various stages of sorafenib treatment","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-06T14:45:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005663","title":"PDX_models_from_Latin_America_WES_","description":"Acral melanoma (AM) is a subtype of cutaneous melanoma that occurs on glabrous skin of the hands and feet (palms, soles and nail apparatus) and which is relatively more common in non-European descent populations such as those of Latin America. Compared to other subtypes, it is poorly studied and experimental models that faithfully reproduce human AM features are urgently needed. We report the generation and preliminary characterisation of a collection of patient-derived xenografts of acral melanomas (AM-PDX) from Latin-American patients. PDX came from Brazilian and Mexican patients cared for at the Instituto Nacional de Câncer (INCA) and the Instituto Nacional de Cancerologia (INCan). The majority of the samples are acral lentiginous melanomas, ulcerated, with &gt; 4mm Breslow depth and &gt; 2 mitosis / mm2. Samples were mechanically fragmented and subcutaneously implanted in NSG mice and then collected for molecular analysis.","abstract":"Acral melanoma (AM) is a subtype of cutaneous melanoma that occurs on glabrous skin of the hands and feet (palms, soles and nail apparatus) and which is relatively more common in non-European descent populations such as those of Latin America. Compared to other subtypes, it is poorly studied and experimental models that faithfully reproduce human AM features are urgently needed. We report the generation and preliminary characterisation of a collection of patient-derived xenografts of acral melanomas (AM-PDX) from Latin-American patients. PDX came from Brazilian and Mexican patients cared for at the Instituto Nacional de Câncer (INCA) and the Instituto Nacional de Cancerologia (INCan). The majority of the samples are acral lentiginous melanomas, ulcerated, with &gt; 4mm Breslow depth and &gt; 2 mitosis / mm2. Samples were mechanically fragmented and subcutaneously implanted in NSG mice and then collected for molecular analysis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-07T11:08:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005664","title":"BARIA baseline first 100 individuals, RNAseq","description":"Prevalence of obesity and associated diseases, including type 2 diabetes mellitus, dyslipidaemia and non-alcoholic fatty liver disease (NAFLD), are increasing. Underlying mechanisms, especially in humans, are unclear. Bariatric surgery provides the unique opportunity to obtain biopsies and portal vein blood-samples.\n\nMethods\nThe BARIA Study aims to assess how microbiota and their metabolites affect transcription in key tissues and clinical outcome in obese subjects and how baseline anthropometric and metabolic characteristics determine weight loss and glucose homeostasis after bariatric surgery. We phenotype patients undergoing bariatric surgery (predominantly laparoscopic Roux-en-Y gastric bypass), before weight loss, with biometrics, dietary and psychological questionnaires, mixed meal test (MMT) and collect fecal-samples and intra-operative biopsies from liver, adipose tissues and jejunum. We aim to include 1500 patients. A subset (approximately 25%) will undergo intra-operative portal vein blood-sampling. Fecal-samples are analyzed with shotgun metagenomics and targeted metabolomics, fasted and postprandial plasma-samples are subjected to metabolomics, and RNA is extracted from the tissues for RNAseq-analyses. Data will be integrated using state-of-the-art neuronal networks and metabolic modeling.","abstract":"Prevalence of obesity and associated diseases, including type 2 diabetes mellitus, dyslipidaemia and non-alcoholic fatty liver disease (NAFLD), are increasing. Underlying mechanisms, especially in humans, are unclear. Bariatric surgery provides the unique opportunity to obtain biopsies and portal vein blood-samples.\n\nMethods\nThe BARIA Study aims to assess how microbiota and their metabolites affect transcription in key tissues and clinical outcome in obese subjects and how baseline anthropometric and metabolic characteristics determine weight loss and glucose homeostasis after bariatric surgery. We phenotype patients undergoing bariatric surgery (predominantly laparoscopic Roux-en-Y gastric bypass), before weight loss, with biometrics, dietary and psychological questionnaires, mixed meal test (MMT) and collect fecal-samples and intra-operative biopsies from liver, adipose tissues and jejunum. We aim to include 1500 patients. A subset (approximately 25%) will undergo intra-operative portal vein blood-sampling. Fecal-samples are analyzed with shotgun metagenomics and targeted metabolomics, fasted and postprandial plasma-samples are subjected to metabolomics, and RNA is extracted from the tissues for RNAseq-analyses. Data will be integrated using state-of-the-art neuronal networks and metabolic modeling.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005665","title":"DGCR8 and the six hit, three-step model of schwannomatosis","description":"In our manuscript, we report the second case of a patient with peripheral schwannomatosis and thyroid alterations cause by the germline pathogenic variant E518K in DGCR8 and analyzed a total of 13 schwannomas from patients in the two kindreds identified up to date. Our analyses revealed how path to tumorigenesis prompted by DGCR8 requires the loss of the wild type allele of Chrm22q and in more than two thirds of the tumors a complete inactivation of NF2.","abstract":"In our manuscript, we report the second case of a patient with peripheral schwannomatosis and thyroid alterations cause by the germline pathogenic variant E518K in DGCR8 and analyzed a total of 13 schwannomas from patients in the two kindreds identified up to date. Our analyses revealed how path to tumorigenesis prompted by DGCR8 requires the loss of the wild type allele of Chrm22q and in more than two thirds of the tumors a complete inactivation of NF2.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-07T14:27:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005666","title":"Perturbed NK Cell Homeostasis Associated with Disease Severity in Chronic Neutropenia","description":null,"abstract":"Neutrophils have been suggested to play a critical role in terminal differentiation of NK cells. Whether this is a direct effect or a consequence of global immune changes with effects on NK cell homeostasis remains unknown. Here, we used high-resolution flow- and mass cytometry to examine NK cell repertoires in 64 patients with neutropenia and 27 healthy age- and gender-matched donors. A subgroup of patients with chronic neutropenia showed severely disrupted NK cell homeostasis manifested as increased frequencies of CD56bright NK cells and a lack of mature CD56dim NK cells. These immature NK cell repertoires were characterized by expression of proliferation/exhaustion markers Ki-67, Tim-3 and TIGIT and displayed blunted tumor target cell responses. Systems-level immune mapping revealed that the changes in immunophenotypes were confined to NK cells, leaving T cell differentiation intact. RNA sequencing of NK cells from these patients showed upregulation of a network of genes, including TNFSF9, CENPF, MKI67 and TOP2A, associated with apoptosis and the cell cycle, different from conventional CD56bright signatures. Profiling of 249 plasma proteins showed a coordinated enrichment of pathways related to apoptosis and cell turnover, which correlated with immature NK cell repertoires. Notably, most of these patients exhibited severe-grade neutropenia, suggesting that the profoundly altered NK cell homeostasis was connected to the severity of their underlying etiology. Hence, although our data suggests that neutrophils are dispensable for NK cell development and differentiation, some patients displayed a specific gap in the NK repertoire, associated with poor cytotoxic function and more severe disease manifestations.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005667","title":"Surgery in combination with immune checkpoint therapy as an effective treatment for patients with metastatic cancer.","description":"Abstract\r\nSurgical removal of primary tumors was shown to reverse tumor-mediated immune suppression in pre-clinical models with metastatic disease. However, how cytoreductive surgery in the metastatic setting modulates the immune responses in patients, especially in the context of immune checkpoint therapy (ICT)-containing treatments is not understood. Here, we report the first prospective, non-comparative clinical trial (N=104) using three different ICT-containing strategies plus cytoreductive or “debulking” surgery to remove the primary tumor-bearing kidney or a metastatic lesion as a treatment for patients (N=43) with metastatic clear cell renal cell carcinoma (mccRCC). For those patients (N=61) who were not candidates for cytoreductive surgery, a biopsy  was obtained instead for correlative biological studies. Our data demonstrated that the combination of ICT with cytoreductive surgery was safe and feasible in patients with mccRCC. The 2-year overall survival was 84% with a median OS of 54.7 months for patients who received ICT containing regimens plus surgery. Immune-monitoring studies with co-detection by indexing (CODEX) identified distinct tumor spatial conformation of cellular subsets as a novel and improved predictor of response to ICT. Importantly, single-cell RNA-sequencing data demonstrated that surgical removal of the tumor increased antigen-presenting dendritic cell population with a concurrent reduction in KDM6B expressing immune-suppressive myeloid cells in the peripheral blood. Together, this study highlighted the feasibility of combining ICT with cytoreductive surgery in a metastatic setting and demonstrated potential enhancement of immune responses following ICT plus cytoreductive surgery in patients with metastatic disease.","abstract":"Patients with stage 4 cancer generally have a dismal prognosis and eventually die from metastasis. Surgery to remove the primary cancer or metastasis is usually not recommended for treating metastatic cancer. However, in the era of novel immune checkpoint therapy (ICT), it is not known whether surgery can be safely combined with ICT to provide survival benefit for patients with metastatic cancer. Therefore, we designed a prospective, randomized, pilot clinical trial with a combination of surgery and different forms of ICT for the treatment of patients with metastatic renal cell carcinoma (RCC). Patients on this trial received ICT followed by cytoreductive surgery (CRS) consisting of nephrectomy (removal of primary tumor in the kidney) or metastasectomy (removal of metastatic lesions), or to biopsy (not counted as CRS) then continued with maintenance ICT for up to 2 years. Our data indicate that CRS can be safely combined with ICT without increasing surgical complications. For patients who had CRS plus ICT, 2-year overall survival (OS) rate is 86% and median OS has not yet been reached with median follow-up of 36.8 months. For patients who only received ICT, 2-year OS rate is 48% and median OS is 20.1 months. We have also identified a number of potential genomic and immunologic biomarkers that correlate with clinical benefits. Our study represents an initial pilot trial to demonstrate the feasibility of combining surgery with ICT for patients with metastatic disease. This combination approach warrants additional studies to improve clinical outcomes for patients with metastatic cancers.","study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-11T11:10:57.341112+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005668","title":"Perturbing_T_cell_activation_circuitries_at_single_cell_resolution","description":"Genome-wide association studies (GWAS) have successfully identified thousands of genetic variants associated with complex immune-mediated diseases, such as inflammatory bowel disease (IBD) and rheumatoid arthritis. These genetic links provide critical clues to processes underlying disease biology and increase the chances of development of successful therapeutic targets. However, the mechanisms by which GWAS variants increase disease susceptibility are difficult to unravel since most of them lie in non-coding areas of the genome 1. Thus, we first need to identify: 1) in which cell types (and specific cellular states) these genetic variants are relevant, 2) what are the causal genes affecting disease susceptibility and 3) what are the function of these genes in different cell states. Several studies have placed CD4+ T cells as central effectors during immune dysregulation in disease pathology. Our work within the Open Targets Consortium demonstrated that immune disease variants point towards genetic dysregulation of CD4+ memory T cells. Memory T cells possess many differences from naïve T cells that contribute to their efficiency to promptly promote secondary immune responses. We showed that rather than falling into distinct populations, naive and memory cells form a transcriptional continuum of cell states from naïve through central to effector memory T cells. This effectorness gradient influences the response of T cells to the environment. This implies that these differences may also affect how disease-genes modulate naïve and memory cell activation and therefore needs to be studied through single cell approaches. To unveil new links between disease risk variants, genes and activation states, we mapped single-cell eQTLs in memory and naive T cells at resting state or 16, 40 and 120 hours after activation. We identified over 3000 eQTL signals in this dataset at different time points. By combining these data with existing GWAS signals we are identifying hundreds of genes for which sc-eQTL and GWAS variants colocalise, therefore implicating shared causal mechanisms between the gene expression and disease-traits. Here, we propose to build on these data by using CRISPR screens in combination with single cell RNA-sequencing to evaluate the effects of disease candidate genes (identified in our colocalisation studies) on T cell activation.","abstract":"We aim to understand how perturbation of disease-genes affect T cell activation in naive and memory T cells, using cutting edge single cell CRISPR screens. This project will be developed in two phases, the pilot phase will define genes of interest and will test the technology. The second phase will comprise the main screen, data analysis and integration with other datasets available in the Trynka team. \n\nOur experiments will: 1) unveil the phenotypic consequences of disease-associated genes in T cells, 2) identify the biological pathways these genes are interacting with and 3) identify genes that have distinct effects in T cell populations, building on our knowledge of how memory and naive T cells contribute to disease pathology.\n\nWe are curating information on candidate-genes identified by our colocalisation studies. These data include gene function, subcellular location, mutation intolerance scores and tractability. We want to use single cell transcriptomics as readout to assess the impact of gene knockouts on T cell activation. Here, we ask funds to develop a small lentiviral CRISPR library (with 20 prioritised candidate genes) for single cell RNA-sequencing readout in naïve and memory T cells. For this, we will have the support of Sanger Gene Editing Team to design and prepare custom lentiviral libraries. These experiments will provide us with valuable pilot data that will inform the set up for a larger scale project.\n.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005669","title":"SudanMitoSeq: Sudanese mitochondrial sequencing","description":"In various contexts, mitochondrial function or dysfunction can be linked to mitochondrial genome variations. The use of mitochondrial genetics thus promises personalized diagnostics and treatments. In order to devise specific precision medicine approaches based on mitochondrial genetic variation and to test them within clinical studies, control data is indispensable. Such control data needs to comprehensively cover genetic variation commonly observed and thus expected. In the context of this study we assessed whether current, world-wide mitochondrial data sufficiently represents the region of North and East Africa, that is, whether current reference data is ready for precision medicine in this region. Towards this, we sequenced mitochondrial genomes of 159 Sudanese individuals provided as part of this EGA study and analyzed them together with various other, publicly available data concerning mitochondrial variation. For details, please refer to the publication.","abstract":"In various contexts, mitochondrial function or dysfunction can be linked to mitochondrial genome variations. The use of mitochondrial genetics thus promises personalized diagnostics and treatments. In order to devise specific precision medicine approaches based on mitochondrial genetic variation and to test them within clinical studies, control data is indispensable. Such control data needs to comprehensively cover genetic variation commonly observed and thus expected. In the context of this study we assessed whether current, world-wide mitochondrial data sufficiently represents the region of North and East Africa, that is, whether current reference data is ready for precision medicine in this region. Towards this, we sequenced mitochondrial genomes of 159 Sudanese individuals provided as part of this EGA study and analyzed them together with various other, publicly available data concerning mitochondrial variation. For details, please refer to the publication.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-13T07:31:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005670","title":"Small variants in mtDNA Canary Islands - WGS Illumina (ITER)","description":"The mitochondrial genome (mtDNA) is of interest for a range of fields including evolutionary, forensic, and medical genetics. Human mitogenomes can be classified into evolutionary related haplogroups that provide ancestral information and pedigree relationships. Because of this and the advent of high-throughput sequencing (HTS) technology, there is a diversity of bioinformatic tools for haplogroup classification. We present a benchmarking of the 11 most salient tools for human mtDNA classification using empirical whole-genome (WGS) and whole-exome (WES) short-read sequencing data from 36 unrelated donors. Besides, because of its relevance, we also assess the best performing tool in third-generation long noisy read WGS data obtained with nanopore technology for a subset of the donors. We found that, for short-read WGS, most of the tools exhibit high accuracy for haplogroup classification irrespective of the input file used for the analysis. However, for short- read WES, Haplocheck and MixEmt were the most accurate tools. Based on the performance shown for WGS and WES, and the accompanying qualitative assessment, Haplocheck stands out as the most complete tool. For third-generation HTS data, we also showed that Haplocheck was able to accurately retrieve mtDNA haplogroups for all samples assessed, although only after following assembly-based approaches (either based on a referenced-based assembly or a hybrid de novo assembly). Taken together, our results provide guidance for researchers to select the most suitable tool to conduct the mtDNA analyses from HTS data.","abstract":"The mitochondrial genome (mtDNA) is of interest for a range of fields including evolutionary, forensic, and medical genetics. Human mitogenomes can be classified into evolutionary related haplogroups that provide ancestral information and pedigree relationships. Because of this and the advent of high-throughput sequencing (HTS) technology, there is a diversity of bioinformatic tools for haplogroup classification. We present a benchmarking of the 11 most salient tools for human mtDNA classification using empirical whole-genome (WGS) and whole-exome (WES) short-read sequencing data from 36 unrelated donors. Besides, because of its relevance, we also assess the best performing tool in third-generation long noisy read WGS data obtained with nanopore technology for a subset of the donors. We found that, for short-read WGS, most of the tools exhibit high accuracy for haplogroup classification irrespective of the input file used for the analysis. However, for short- read WES, Haplocheck and MixEmt were the most accurate tools. Based on the performance shown for WGS and WES, and the accompanying qualitative assessment, Haplocheck stands out as the most complete tool. For third-generation HTS data, we also showed that Haplocheck was able to accurately retrieve mtDNA haplogroups for all samples assessed, although only after following assembly-based approaches (either based on a referenced-based assembly or a hybrid de novo assembly). Taken together, our results provide guidance for researchers to select the most suitable tool to conduct the mtDNA analyses from HTS data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005671","title":"Small variants in mtDNA Canary Islands - WGS Oxford Nanopore Technologies (ITER)","description":"The mitochondrial genome (mtDNA) is of interest for a range of fields including evolutionary, forensic, and medical genetics. Human mitogenomes can be classified into evolutionary related haplogroups that provide ancestral information and pedigree relationships. Because of this and the advent of high-throughput sequencing (HTS) technology, there is a diversity of bioinformatic tools for haplogroup classification. We present a benchmarking of the 11 most salient tools for human mtDNA classification using empirical whole-genome (WGS) and whole-exome (WES) short-read sequencing data from 36 unrelated donors. Besides, because of its relevance, we also assess the best performing tool in third-generation long noisy read WGS data obtained with nanopore technology for a subset of the donors. We found that, for short-read WGS, most of the tools exhibit high accuracy for haplogroup classification irrespective of the input file used for the analysis. However, for short- read WES, Haplocheck and MixEmt were the most accurate tools. Based on the performance shown for WGS and WES, and the accompanying qualitative assessment, Haplocheck stands out as the most complete tool. For third-generation HTS data, we also showed that Haplocheck was able to accurately retrieve mtDNA haplogroups for all samples assessed, although only after following assembly-based approaches (either based on a referenced-based assembly or a hybrid de novo assembly). Taken together, our results provide guidance for researchers to select the most suitable tool to conduct the mtDNA analyses from HTS data.","abstract":"The mitochondrial genome (mtDNA) is of interest for a range of fields including evolutionary, forensic, and medical genetics. Human mitogenomes can be classified into evolutionary related haplogroups that provide ancestral information and pedigree relationships. Because of this and the advent of high-throughput sequencing (HTS) technology, there is a diversity of bioinformatic tools for haplogroup classification. We present a benchmarking of the 11 most salient tools for human mtDNA classification using empirical whole-genome (WGS) and whole-exome (WES) short-read sequencing data from 36 unrelated donors. Besides, because of its relevance, we also assess the best performing tool in third-generation long noisy read WGS data obtained with nanopore technology for a subset of the donors. We found that, for short-read WGS, most of the tools exhibit high accuracy for haplogroup classification irrespective of the input file used for the analysis. However, for short- read WES, Haplocheck and MixEmt were the most accurate tools. Based on the performance shown for WGS and WES, and the accompanying qualitative assessment, Haplocheck stands out as the most complete tool. For third-generation HTS data, we also showed that Haplocheck was able to accurately retrieve mtDNA haplogroups for all samples assessed, although only after following assembly-based approaches (either based on a referenced-based assembly or a hybrid de novo assembly). Taken together, our results provide guidance for researchers to select the most suitable tool to conduct the mtDNA analyses from HTS data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005672","title":"Small variants in mtDNA Canary Islands - WES Illumina (ITER)","description":"The mitochondrial genome (mtDNA) is of interest for a range of fields including evolutionary, forensic, and medical genetics. Human mitogenomes can be classified into evolutionary related haplogroups that provide ancestral information and pedigree relationships. Because of this and the advent of high-throughput sequencing (HTS) technology, there is a diversity of bioinformatic tools for haplogroup classification. We present a benchmarking of the 11 most salient tools for human mtDNA classification using empirical whole-genome (WGS) and whole-exome (WES) short-read sequencing data from 36 unrelated donors. Besides, because of its relevance, we also assess the best performing tool in third-generation long noisy read WGS data obtained with nanopore technology for a subset of the donors. We found that, for short-read WGS, most of the tools exhibit high accuracy for haplogroup classification irrespective of the input file used for the analysis. However, for short- read WES, Haplocheck and MixEmt were the most accurate tools. Based on the performance shown for WGS and WES, and the accompanying qualitative assessment, Haplocheck stands out as the most complete tool. For third-generation HTS data, we also showed that Haplocheck was able to accurately retrieve mtDNA haplogroups for all samples assessed, although only after following assembly-based approaches (either based on a referenced-based assembly or a hybrid de novo assembly). Taken together, our results provide guidance for researchers to select the most suitable tool to conduct the mtDNA analyses from HTS data.","abstract":"The mitochondrial genome (mtDNA) is of interest for a range of fields including evolutionary, forensic, and medical genetics. Human mitogenomes can be classified into evolutionary related haplogroups that provide ancestral information and pedigree relationships. Because of this and the advent of high-throughput sequencing (HTS) technology, there is a diversity of bioinformatic tools for haplogroup classification. We present a benchmarking of the 11 most salient tools for human mtDNA classification using empirical whole-genome (WGS) and whole-exome (WES) short-read sequencing data from 36 unrelated donors. Besides, because of its relevance, we also assess the best performing tool in third-generation long noisy read WGS data obtained with nanopore technology for a subset of the donors. We found that, for short-read WGS, most of the tools exhibit high accuracy for haplogroup classification irrespective of the input file used for the analysis. However, for short- read WES, Haplocheck and MixEmt were the most accurate tools. Based on the performance shown for WGS and WES, and the accompanying qualitative assessment, Haplocheck stands out as the most complete tool. For third-generation HTS data, we also showed that Haplocheck was able to accurately retrieve mtDNA haplogroups for all samples assessed, although only after following assembly-based approaches (either based on a referenced-based assembly or a hybrid de novo assembly). Taken together, our results provide guidance for researchers to select the most suitable tool to conduct the mtDNA analyses from HTS data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005673","title":"Whole exome sequencing of Congenital Cataract","description":"Whole exome sequencing to identify potentially relevant mutations of congenital cataract in a Chinese girl.\nThe novel PAX6 mutation (c.221G&gt;A) is associated with congenital cataract, and the WFS1 mutation (c.2070_2079del) interactively aggravates this process.","abstract":"Whole exome sequencing to identify potentially relevant mutations of congenital cataract in a Chinese girl.\nThe novel PAX6 mutation (c.221G&gt;A) is associated with congenital cataract, and the WFS1 mutation (c.2070_2079del) interactively aggravates this process.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-15T01:13:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005674","title":"Whole-genome sequencing using Nanopore technology Pilot for UK Biobank Human Genome Samples","description":"Six UK biobank participant samples were sequenced using the Oxford Nanopore PromethION as part of a wider study on the application of long read sequencing methods to large cohort projects. This data deposit contains only Oxford Nanopore Data and should be considered with the wider dataset. All sequence data were generated using and Oxford Nanopore PromethION Beta device in early 2019.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001005675","title":"Germline biallelic mutation affecting the transcription factor Helios causes pleiotropic defects of immunity","description":"We studied a patient with recurrent respiratory infections and hypogammaglobulinemia and identified a germline homozygous missense mutation in IKZF2 encoding Helios (p.Ile325Val). \n\nWe show that HeliosI325V retains DNA-binding and dimerization properties, but loses interaction with several partners, including epigenetic remodelers HDAC1, HDAC3 and the ATAC complex. \n\nSingle-cell RNA-sequencing of peripheral blood mononuclear cells revealed gene expression signatures indicative of a shift towards pro-inflammatory, effector-like status in the patient’s T cells.\n\nWe observed an upregulation of the anti-inflammatory gene, TSC22D3, encoding the glucocorticoid-induced leucine zipper (GILZ), whose expression was reported to increase upon IL-2 deprivation. \n\nWe validated this finding in primary T cells, where we observed a pronounced reduction in IL-2 production upon their stimulation, together with a defect in their ability to proliferate, rendering them more anergic. \n\nCollectively, we identify a novel germline-encoded inborn error of immunity and define a role for Helios in conventional T cells, whereby interactions with specific binding partners is necessary to mediate the transcriptional programs that enable T-cell homeostasis in health and disease.","abstract":"We studied a patient with recurrent respiratory infections and hypogammaglobulinemia and identified a germline homozygous missense mutation in IKZF2 encoding Helios (p.Ile325Val). \n\nWe show that HeliosI325V retains DNA-binding and dimerization properties, but loses interaction with several partners, including epigenetic remodelers HDAC1, HDAC3 and the ATAC complex. \n\nSingle-cell RNA-sequencing of peripheral blood mononuclear cells revealed gene expression signatures indicative of a shift towards pro-inflammatory, effector-like status in the patient’s T cells.\n\nWe observed an upregulation of the anti-inflammatory gene, TSC22D3, encoding the glucocorticoid-induced leucine zipper (GILZ), whose expression was reported to increase upon IL-2 deprivation. \n\nWe validated this finding in primary T cells, where we observed a pronounced reduction in IL-2 production upon their stimulation, together with a defect in their ability to proliferate, rendering them more anergic. \n\nCollectively, we identify a novel germline-encoded inborn error of immunity and define a role for Helios in conventional T cells, whereby interactions with specific binding partners is necessary to mediate the transcriptional programs that enable T-cell homeostasis in health and disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-15T13:00:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005676","title":"Identification of biomarkers of response to preoperative talazoparib monotherapy  in treatment naïve gBRCA+ breast cancers","description":"Germline mutations in BRCA1 or BRCA2 exist in ~2-7% of breast cancer patients, which has led to the approval of PARP inhibitors in the advanced setting.  We have previously reported a phase II neoadjuvant trial of single agent talazoparib for patients with germline BRCA pathogenic variants with a pathologic complete response (pCR) rate of 53%.  As nearly half of the patients treated did not have pCR, better strategies are needed to overcome treatment resistance.  To this end, we conducted multi-omic analysis of 13 treatment naïve breast cancer tumors from patients that went on to receive single-agent neoadjuvant talazoparib.  We looked for biomarkers that were predictive of response (assessed by residual cancer burden) after 6 months of therapy.  We found that all resistant tumors exhibited either the loss of SHLD2, expression of a hypoxia signature, or expression of a stem cell signature.  These results indicate that the deep analysis of pre-treatment tumors can identify biomarkers that are predictive of response to talazoparib and potentially other PARP inhibitors, and provides a framework that will allow for better selection of patients for treatment, as well as a roadmap for the development of novel combination therapies to prevent emergence of resistance.","abstract":"Germline mutations in BRCA1 or BRCA2 exist in ~2-7% of breast cancer patients, which has led to the approval of PARP inhibitors in the advanced setting.  We have previously reported a phase II neoadjuvant trial of single agent talazoparib for patients with germline BRCA pathogenic variants with a pathologic complete response (pCR) rate of 53%.  As nearly half of the patients treated did not have pCR, better strategies are needed to overcome treatment resistance.  To this end, we conducted multi-omic analysis of 13 treatment naïve breast cancer tumors from patients that went on to receive single-agent neoadjuvant talazoparib.  We looked for biomarkers that were predictive of response (assessed by residual cancer burden) after 6 months of therapy.  We found that all resistant tumors exhibited either the loss of SHLD2, expression of a hypoxia signature, or expression of a stem cell signature.  These results indicate that the deep analysis of pre-treatment tumors can identify biomarkers that are predictive of response to talazoparib and potentially other PARP inhibitors, and provides a framework that will allow for better selection of patients for treatment, as well as a roadmap for the development of novel combination therapies to prevent emergence of resistance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-18T06:02:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005677","title":"Small variants in mtDNA Canary Islands - WGS Oxford Nanopore Technologies (ITER)","description":"The mitochondrial genome (mtDNA) is of interest for a range of fields including evolutionary, forensic, and medical genetics. Human mitogenomes can be classified into evolutionary related haplogroups that provide ancestral information and pedigree relationships. Because of this and the advent of high-throughput sequencing (HTS) technology, there is a diversity of bioinformatic tools for haplogroup classification. We present a benchmarking of the 11 most salient tools for human mtDNA classification using empirical whole-genome (WGS) and whole-exome (WES) short-read sequencing data from 36 unrelated donors. Besides, because of its relevance, we also assess the best performing tool in third-generation long noisy read WGS data obtained with nanopore technology for a subset of the donors. We found that, for short-read WGS, most of the tools exhibit high accuracy for haplogroup classification irrespective of the input file used for the analysis. However, for short- read WES, Haplocheck and MixEmt were the most accurate tools. Based on the performance shown for WGS and WES, and the accompanying qualitative assessment, Haplocheck stands out as the most complete tool. For third-generation HTS data, we also showed that Haplocheck was able to accurately retrieve mtDNA haplogroups for all samples assessed, although only after following assembly-based approaches (either based on a referenced-based assembly or a hybrid de novo assembly). Taken together, our results provide guidance for researchers to select the most suitable tool to conduct the mtDNA analyses from HTS data.","abstract":"The mitochondrial genome (mtDNA) is of interest for a range of fields including evolutionary, forensic, and medical genetics. Human mitogenomes can be classified into evolutionary related haplogroups that provide ancestral information and pedigree relationships. Because of this and the advent of high-throughput sequencing (HTS) technology, there is a diversity of bioinformatic tools for haplogroup classification. We present a benchmarking of the 11 most salient tools for human mtDNA classification using empirical whole-genome (WGS) and whole-exome (WES) short-read sequencing data from 36 unrelated donors. Besides, because of its relevance, we also assess the best performing tool in third-generation long noisy read WGS data obtained with nanopore technology for a subset of the donors. We found that, for short-read WGS, most of the tools exhibit high accuracy for haplogroup classification irrespective of the input file used for the analysis. However, for short- read WES, Haplocheck and MixEmt were the most accurate tools. Based on the performance shown for WGS and WES, and the accompanying qualitative assessment, Haplocheck stands out as the most complete tool. For third-generation HTS data, we also showed that Haplocheck was able to accurately retrieve mtDNA haplogroups for all samples assessed, although only after following assembly-based approaches (either based on a referenced-based assembly or a hybrid de novo assembly). Taken together, our results provide guidance for researchers to select the most suitable tool to conduct the mtDNA analyses from HTS data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-18T11:47:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005678","title":"Small variants in mtDNA Canary Islands - WES Illumina (ITER)","description":"The mitochondrial genome (mtDNA) is of interest for a range of fields including evolutionary, forensic, and medical genetics. Human mitogenomes can be classified into evolutionary related haplogroups that provide ancestral information and pedigree relationships. Because of this and the advent of high-throughput sequencing (HTS) technology, there is a diversity of bioinformatic tools for haplogroup classification. We present a benchmarking of the 11 most salient tools for human mtDNA classification using empirical whole-genome (WGS) and whole-exome (WES) short-read sequencing data from 36 unrelated donors. Besides, because of its relevance, we also assess the best performing tool in third-generation long noisy read WGS data obtained with nanopore technology for a subset of the donors. We found that, for short-read WGS, most of the tools exhibit high accuracy for haplogroup classification irrespective of the input file used for the analysis. However, for short- read WES, Haplocheck and MixEmt were the most accurate tools. Based on the performance shown for WGS and WES, and the accompanying qualitative assessment, Haplocheck stands out as the most complete tool. For third-generation HTS data, we also showed that Haplocheck was able to accurately retrieve mtDNA haplogroups for all samples assessed, although only after following assembly-based approaches (either based on a referenced-based assembly or a hybrid de novo assembly). Taken together, our results provide guidance for researchers to select the most suitable tool to conduct the mtDNA analyses from HTS data.","abstract":"The mitochondrial genome (mtDNA) is of interest for a range of fields including evolutionary, forensic, and medical genetics. Human mitogenomes can be classified into evolutionary related haplogroups that provide ancestral information and pedigree relationships. Because of this and the advent of high-throughput sequencing (HTS) technology, there is a diversity of bioinformatic tools for haplogroup classification. We present a benchmarking of the 11 most salient tools for human mtDNA classification using empirical whole-genome (WGS) and whole-exome (WES) short-read sequencing data from 36 unrelated donors. Besides, because of its relevance, we also assess the best performing tool in third-generation long noisy read WGS data obtained with nanopore technology for a subset of the donors. We found that, for short-read WGS, most of the tools exhibit high accuracy for haplogroup classification irrespective of the input file used for the analysis. However, for short- read WES, Haplocheck and MixEmt were the most accurate tools. Based on the performance shown for WGS and WES, and the accompanying qualitative assessment, Haplocheck stands out as the most complete tool. For third-generation HTS data, we also showed that Haplocheck was able to accurately retrieve mtDNA haplogroups for all samples assessed, although only after following assembly-based approaches (either based on a referenced-based assembly or a hybrid de novo assembly). Taken together, our results provide guidance for researchers to select the most suitable tool to conduct the mtDNA analyses from HTS data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-18T11:47:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005679","title":"Small variants in mtDNA Canary Islands - WGS Illumina (ITER)","description":"The mitochondrial genome (mtDNA) is of interest for a range of fields including evolutionary, forensic, and medical genetics. Human mitogenomes can be classified into evolutionary related haplogroups that provide ancestral information and pedigree relationships. Because of this and the advent of high-throughput sequencing (HTS) technology, there is a diversity of bioinformatic tools for haplogroup classification. We present a benchmarking of the 11 most salient tools for human mtDNA classification using empirical whole-genome (WGS) and whole-exome (WES) short-read sequencing data from 36 unrelated donors. Besides, because of its relevance, we also assess the best performing tool in third-generation long noisy read WGS data obtained with nanopore technology for a subset of the donors. We found that, for short-read WGS, most of the tools exhibit high accuracy for haplogroup classification irrespective of the input file used for the analysis. However, for short- read WES, Haplocheck and MixEmt were the most accurate tools. Based on the performance shown for WGS and WES, and the accompanying qualitative assessment, Haplocheck stands out as the most complete tool. For third-generation HTS data, we also showed that Haplocheck was able to accurately retrieve mtDNA haplogroups for all samples assessed, although only after following assembly-based approaches (either based on a referenced-based assembly or a hybrid de novo assembly). Taken together, our results provide guidance for researchers to select the most suitable tool to conduct the mtDNA analyses from HTS data.","abstract":"The mitochondrial genome (mtDNA) is of interest for a range of fields including evolutionary, forensic, and medical genetics. Human mitogenomes can be classified into evolutionary related haplogroups that provide ancestral information and pedigree relationships. Because of this and the advent of high-throughput sequencing (HTS) technology, there is a diversity of bioinformatic tools for haplogroup classification. We present a benchmarking of the 11 most salient tools for human mtDNA classification using empirical whole-genome (WGS) and whole-exome (WES) short-read sequencing data from 36 unrelated donors. Besides, because of its relevance, we also assess the best performing tool in third-generation long noisy read WGS data obtained with nanopore technology for a subset of the donors. We found that, for short-read WGS, most of the tools exhibit high accuracy for haplogroup classification irrespective of the input file used for the analysis. However, for short- read WES, Haplocheck and MixEmt were the most accurate tools. Based on the performance shown for WGS and WES, and the accompanying qualitative assessment, Haplocheck stands out as the most complete tool. For third-generation HTS data, we also showed that Haplocheck was able to accurately retrieve mtDNA haplogroups for all samples assessed, although only after following assembly-based approaches (either based on a referenced-based assembly or a hybrid de novo assembly). Taken together, our results provide guidance for researchers to select the most suitable tool to conduct the mtDNA analyses from HTS data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-18T11:47:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005680","title":"Targeted sequencing of candidate regions on chromosome 22q predisposing to multiple schwannomas","description":"Constitutional LZTR1 or SMARCB1 pathogenic variants have been found in ~86% of familial and ~40% of sporadic schwannomatosis cases. Hence, we performed massively parallel sequencing of the entire LZTR1, SMARCB1 and NF2 genomic loci in 35 individuals with schwannomas negative for constitutional first-hit pathogenic variants in the LZTR1/SMARCB1/NF2 coding sequences, however with 22q deletion and/or a different NF2 pathogenic variant in each tumor, including six cases with only one tumor available. Furthermore, we verified whether any other LZTR1/SMARCB1/NF2 (likely) pathogenic variant(s) could be found in 16 cases carrying a SMARCB1 constitutional variant in the 3’ untranslated region (3’-UTR) c.*17C&gt;T, c.*70C&gt;T or c.*82C&gt;T. As no additional variants were found, functional studies were performed to clarify the effect of these 3’-UTR variants on the transcript. The 3’-UTR variants c.*17C&gt;T and c.*82C&gt;T showed pathogenicity by negatively affecting SMARCB1 transcript level. Two novel deep intronic SMARCB1 variants, c.500+883T&gt;G and c.500+887G&gt;A, resulting in out-of-frame missplicing of intron 4, were identified in two unrelated individuals. Further resequencing of the entire repeat - masked genomics sequences of chromosome 22q in individuals negative for pathogenic variants in the SMARCB1/LZTR1/NF2 coding- and non-coding regions revealed five potential schwannomatosis-predisposing candidate genes, i.e. MYO18B, NEFH, SGSM1, SGSM3 and SBF1, pending further verification.","abstract":"Constitutional LZTR1 or SMARCB1 pathogenic variants have been found in ~86% of familial and ~40% of sporadic schwannomatosis cases. Hence, we performed massively parallel sequencing of the entire LZTR1, SMARCB1 and NF2 genomic loci in 35 individuals with schwannomas negative for constitutional first-hit pathogenic variants in the LZTR1/SMARCB1/NF2 coding sequences, however with 22q deletion and/or a different NF2 pathogenic variant in each tumor, including six cases with only one tumor available. Furthermore, we verified whether any other LZTR1/SMARCB1/NF2 (likely) pathogenic variant(s) could be found in 16 cases carrying a SMARCB1 constitutional variant in the 3’ untranslated region (3’-UTR) c.*17C&gt;T, c.*70C&gt;T or c.*82C&gt;T. As no additional variants were found, functional studies were performed to clarify the effect of these 3’-UTR variants on the transcript. The 3’-UTR variants c.*17C&gt;T and c.*82C&gt;T showed pathogenicity by negatively affecting SMARCB1 transcript level. Two novel deep intronic SMARCB1 variants, c.500+883T&gt;G and c.500+887G&gt;A, resulting in out-of-frame missplicing of intron 4, were identified in two unrelated individuals. Further resequencing of the entire repeat - masked genomics sequences of chromosome 22q in individuals negative for pathogenic variants in the SMARCB1/LZTR1/NF2 coding- and non-coding regions revealed five potential schwannomatosis-predisposing candidate genes, i.e. MYO18B, NEFH, SGSM1, SGSM3 and SBF1, pending further verification.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-18T12:01:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005681","title":"Disturbed trophoblast transition links early fetal to maternal syndrome progression in pre-eclampsia","description":null,"abstract":"Pre-eclampsia (PE) is a syndrome that affects multiple organ systems and is the most severe hypertensive disorder in pregnancy. It frequently leads to preterm delivery, maternal and fetal morbidity and mortality, and life-long complications. We currently lack efficient screening tools and early therapies to address PE. To study the initial stages of early onset PE and identify candidate markers and pathways, we performed spatio-temporal multi-omics profiling of human PE placentae and healthy controls and validated targets in early gestation in a longitudinal clinical cohort. We used a single nuclei RNA-seq approach combined with spatial proteo- and transcriptomics and mechanistic in vitro signaling analyses. We discovered a key disruption in trophoblast transition, which is driven by the increase of transcriptional coactivator p300 that ultimately ends with a senescence-associated secretory phenotype (SASP) of trophoblasts. We found a significant increase in the senescence marker Activin-A in preeclamptic maternal serum in early gestation, before the development of clinical symptoms, indicating a translation of the fetal syndrome to the maternal side. Our work identifies potential new biomarkers for the early diagnosis of the disease and possible targets for interventions, which would be crucial steps toward protecting the mother and child from gestational mortality and morbidity and an increased risk of cardiovascular disease later in life. This study includes early placentae samples from the fetal part (villi; n=10), maternal part (Decidua; n=3), late placentae samples from healthy pregnancies, villi (n=6), decidua (n=4), and late placentae samples from early onset preeclamptic pregnancies, villi (n=5) and decidua (n=5).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-18T15:12:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005682","title":"Single_cell_multiomics_study_of_male_germline_RNA_","description":"This study aims to undrestand single cell hetrogenity in male reproductive tissues using multi-omics G&amp;T method. Testis biopsy were sorted using cell surface marker to differentation different germline cells and somatic cells. We have sorted three two biposies which we would like to preform a G&amp;T method. The results from this will guid our cell sorting stratgy for the remianing biopsies. Hence, we would like to request to priortis this submission.","abstract":"Studying mutations arising in normal human cells during an individual’s lifetime provides insight into the development, maintenance and structure of normal tissues, the mutational processes that have been operative, and the role of selection in shaping cell populations. In addition, it can elucidate how each of these is altered by, or contribute to, cancer, other diseases, and ageing.\n\nMutations in somatic cells can be caused by genetic and environmental factors, and are persistent in the body through the course of cell division. Characterising somatic mutations has been technically challenging, as normal cell populations consist of myriad small clones with the mutations differing between clones. On the other hand, genetic errors in germline cells are the source of inherited diseases and evolutionary adaptions. A recent study has shown that germline cells have a considerably lower mutation rate compared to their somatic counterparts. However, how this low mutation burden is achieved by the germline cells remains elusive. The answer to this question is critical in the context of disease predisposition for the offspring. This study aims to investigate how factors such as gene expression may protect the germline cells from accruing mutations during the natural process of ageing compared to the soma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005683","title":"Single_cell_multiomics_study_of_male_germline_DNA_","description":"This study aims to understand single cell heterogeneity in male reproductive tissues using multi-omics G&amp;T method. Testis biopsy were sorted using cell surface marker to differentiation different germline cells and somatic cells. We have sorted three two biopsies which we would like to preform a G&amp;T method. The results from this will guide our cell sorting strategy for the remaining biopsies. Hence, we would like to request to prioritise this submission.","abstract":"Studying mutations arising in normal human cells during an individual’s lifetime provides insight into the development, maintenance and structure of normal tissues, the mutational processes that have been operative, and the role of selection in shaping cell populations. In addition, it can elucidate how each of these is altered by, or contribute to, cancer, other diseases, and ageing.\n\nMutations in somatic cells can be caused by genetic and environmental factors, and are persistent in the body through the course of cell division. Characterising somatic mutations has been technically challenging, as normal cell populations consist of myriad small clones with the mutations differing between clones. On the other hand, genetic errors in germline cells are the source of inherited diseases and evolutionary adaptions. A recent study has shown that germline cells have a considerably lower mutation rate compared to their somatic counterparts. However, how this low mutation burden is achieved by the germline cells remains elusive. The answer to this question is critical in the context of disease predisposition for the offspring. This study aims to investigate how factors such as gene expression may protect the germline cells from accruing mutations during the natural process of ageing compared to the soma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005684","title":"MM samples for epigenomic translocation of H3K4me3 broad domains following super-enhancer hijacking","description":"Chromosomal translocations are important drivers of haematological malignancies whereby proto-oncogenes are activated by juxtaposition with super-enhancers, often called enhancer hijacking. To examine this phenomenon we used ChipSeq based on a combination of six histone modifications as follows: H3K4me1, H3K4me3, H3K9me3, H3K27me3, H3K27Ac and H3K36me3. Samples are patient-derived xenografts generated by passaging primary patient CD138+ selected cells through the SCID-rab myeloma mouse model.","abstract":"Chromosomal translocations are important drivers of haematological malignancies whereby proto-oncogenes are activated by juxtaposition with super-enhancers, often called enhancer hijacking. To examine this phenomenon we used ChipSeq based on a combination of six histone modifications as follows: H3K4me1, H3K4me3, H3K9me3, H3K27me3, H3K27Ac and H3K36me3. Samples are patient-derived xenografts generated by passaging primary patient CD138+ selected cells through the SCID-rab myeloma mouse model.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-18T15:35:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005685","title":"Whole Exome Sequencing of Localized Prostate Cancer Patients","description":"We performed whole-exome sequencing on localized prostate cancer patients to validate tumor content as part of a single-cell RNA sequencing study of localized prostate cancer patients.","abstract":"We performed whole-exome sequencing on localized prostate cancer patients to validate tumor content as part of a single-cell RNA sequencing study of localized prostate cancer patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-18T17:54:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005686","title":"MNM - Temporal variability in Quantitative Microbiome Profiles","description":"Daily quantitative microbiome profiling on 713 fecal samples from 20 Belgian women over six weeks, combined with extensive anthropometric measurements, blood panels, dietary data, and stool characteristics.","abstract":"Daily quantitative microbiome profiling on 713 fecal samples from 20 Belgian women over six weeks, combined with extensive anthropometric measurements, blood panels, dietary data, and stool characteristics.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-18T20:26:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005687","title":"Pediatric HGG WES and RNA-Seq","description":"Paediatric high-grade glioma (pHGG) is the leading cause of paediatric brain tumour death. Here we performed RNA and whole exome sequencing on pHGG samples to analyse transcriptomic and genetic alterations associated with this devastating disease, and to understand the relationship between them.","abstract":"Paediatric high-grade glioma (pHGG) is the leading cause of paediatric brain tumour death. Here we performed RNA and whole exome sequencing on pHGG samples to analyse transcriptomic and genetic alterations associated with this devastating disease, and to understand the relationship between them.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-19T10:01:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005688","title":"HCA_Embryo_Foetal_WSSS_Dev_spatial_Sanger","description":"Detailed single cell atlas of whole human embryos","abstract":"We propose to generate an in-depth single cell and spatial atlas of human embryos during late organogenesis, at 6/7 post conception weeks (PCW). We will deploy genomics technologies to profile single cells from dissociated tissues and within intact tissue sections, and deploy cutting-edge computational methods to reconstruct, in silico, a three-dimensional atlas of the whole human embryo. \n\nDetailed single cell atlas of whole human embryos\nDeliverables: Complete whole embryo atlas datasets by high-throughput genomics profiling (single cell RNA-sequencing (scRNA-seq), single nuclear RNA-sequencing (snRNA-seq), and accessible chromatin sequencing (ATAC-seq)); and spatial transcriptomics (ST, e.g. 10x Genomics Visium), in situ sequencing (ISS) and multiplex smFISH analysis of tissue sections.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005689","title":"Ewing's sarcoma sequencing data","description":"This study shares DNA and RNA sequencing data for patients with Ewing's sarcoma","abstract":"This study shares DNA and RNA sequencing data for patients with Ewing's sarcoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-19T17:56:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005690","title":"Wilm's tumor sequencing data","description":"This study shares DNA and RNA sequencing data from Wilm's tumor patients","abstract":"This study shares DNA and RNA sequencing data from Wilm's tumor patients","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-19T17:57:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005691","title":"Single-nucleus transcriptomic profiling of aging Down Syndrome brains","description":"Down syndrome (DS) – trisomy of human chromosome 21 (HSA21) – is characterized by lifelong cognitive impairments and development of neuropathological hallmarks of Alzheimer’s disease (AD). The cellular and molecular modifications responsible for these effects are not understood. Here we performed single-nucleus RNA-sequencing (snRNA-seq) employing both short (Illumina) and long-read (Pacific Biosciences) sequencing technologies on a total of 29 DS and non-DS control prefrontal cortex samples. In DS, the ratio of inhibitory-to-excitatory neurons was significantly increased, which was not observed in previous reports examining sporadic AD.  DS microglial transcriptomes displayed AD-related aging and activation signatures in advance of AD neuropathology, with increased microglial expression of C1q complement genes (associated with dendritic pruning) and the HSA21 transcription factor gene RUNX1.  Long-read sequencing detected vast RNA isoform diversity within and amongst specific cell types including numerous novel sequences that differed between DS and normal brains.  Notably, over 8,000 genes produced RNAs containing intra-exonic junctions (IEJs), including APP that had previously been associated with somatic gene recombination.  These and related results illuminate large-scale cellular and transcriptomic alterations as novel features of the aging DS brain.","abstract":"Down syndrome (DS) – trisomy of human chromosome 21 (HSA21) – is characterized by lifelong cognitive impairments and development of neuropathological hallmarks of Alzheimer’s disease (AD). The cellular and molecular modifications responsible for these effects are not understood. Here we performed single-nucleus RNA-sequencing (snRNA-seq) employing both short (Illumina) and long-read (Pacific Biosciences) sequencing technologies on a total of 29 DS and non-DS control prefrontal cortex samples. In DS, the ratio of inhibitory-to-excitatory neurons was significantly increased, which was not observed in previous reports examining sporadic AD.  DS microglial transcriptomes displayed AD-related aging and activation signatures in advance of AD neuropathology, with increased microglial expression of C1q complement genes (associated with dendritic pruning) and the HSA21 transcription factor gene RUNX1.  Long-read sequencing detected vast RNA isoform diversity within and amongst specific cell types including numerous novel sequences that differed between DS and normal brains.  Notably, over 8,000 genes produced RNAs containing intra-exonic junctions (IEJs), including APP that had previously been associated with somatic gene recombination.  These and related results illuminate large-scale cellular and transcriptomic alterations as novel features of the aging DS brain.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-19T19:24:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005692","title":"Signals of positive selection in Peruvians from three ecological regions","description":"In this study, genome-wide single-nucleotide polymorphism (SNP) data (Illumina Infinium® MEGA array) was gathered for 200 individuals distributed across Perú, and then analyzed to investigate signals of recent positive selection specific to populations living in the high-altitude environments of the Andes, the arid Pacific coast and the Amazon rainforest.","abstract":"In this study, genome-wide single-nucleotide polymorphism (SNP) data (Illumina Infinium® MEGA array) was gathered for 200 individuals distributed across Perú, and then analyzed to investigate signals of recent positive selection specific to populations living in the high-altitude environments of the Andes, the arid Pacific coast and the Amazon rainforest.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-19T21:57:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005693","title":"HCA_Hormone_glands_Vento_RNA","description":"Study of the cross-talk between the hormone-producing glands from embryos at different ages for both males and females.","abstract":"Hormones are chemical messengers that are important in balancing different processing in adult life. They are secreted from hormone-producing glands to the bloodstream to act on distal organs in the body. Usually, they are present at a low amount and for a given time point. Dysregulation of hormonal levels has a direct impact on our physiological and psychological lifestyle. While the adult endocrine system is heavily studied, the molecular basics and dynamics of the endocrine system at embryonic stages are still understudied. As the interaction between hormones is essential for the proper development of the embryo, the activation time of these organs becomes a critical issue when it is related to their maturation during embryonic life. In this project, I will focus on studying the cross-talk between the hormone-producing glands from embryos at different ages for both males and females. I will generate a single-cell atlas by integrating transcriptome and chromatin accessibility state of the major hormone-producing glands, including the hypothalamus, pituitary, adrenal, pancreas, thyroid, gonads and placenta. Biosynthetic, transport and degradation pathways of various hormones will be constructed from transcriptomic data and crossed between the analysed organs to assess inter-organ interactions. Spatial transcriptomics and proteins imaging with be utilised to validate potential targets at the intact tissue level. Later, samples of glands pathologies will be included to study the systemic influence caused by the imbalanced cellular representation of a given organ. The study outcomes are important and of significant impact in understanding the timing and activity of the different hormones during embryonic life and can serve as a reference for studying the potential effect of hormonal imbalance on embryos during pregnancy.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005694","title":"A_strategic_vision_to_drive_the_control_of_enteric_fever_through_vaccination","description":"Transcriptome signatures of acute typhoid infection\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Transcriptome signatures of acute typhoid infection","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005695","title":"A_strategic_vision_to_drive_the_control_of_enteric_fever_through_vaccination","description":"Transcriptome signatures of acute typhoid infection\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Transcriptome signatures of acute typhoid infection","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005696","title":"COVID_19_Challenge_Project_Single_Cell_Profiling","description":"Single-cell profiling of sero-negative and sero-positive humans that were inoculated with SARS-CoV-2. The cellular response during SARS-CoV-2 is profiled using single-cell transcriptomics, CITE-seq and single cell immune profiling, by sampling PBMCs and nasal swabs before and at multiple time points during SARS-CoV-2 infection. This one-of-a-kind cellular map will give unique temporal resolution of how nasal and immune cells respond to SARS-CoV-2 exposure and infection","abstract":"Single-cell profiling of sero-negative and sero-positive humans that were inoculated with SARS-CoV-2. The cellular response during SARS-CoV-2 is profiled using single-cell transcriptomics, CITE-seq and single cell immune profiling, by sampling PBMCs and nasal swabs before and at multiple time points during SARS-CoV-2 infection. This one-of-a-kind cellular map will give unique temporal resolution of how nasal and immune cells respond to SARS-CoV-2 exposure and infection","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-21T09:57:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005697","title":"Single-cell RNA sequencing of a PBMC sample collected from a male with 45,X/48,XYYY karyotype","description":null,"abstract":"We report a 14-year-old boy with mosaic 45,X/48,XYYY karyotype presenting with subtle dysmorphic features and height deficiency, requiring growth hormone therapy. Single-cell RNA sequencing revealed widespread differences in genotype distribution between 45,X and 48,XYYY immune cells, with concordant results at DNA level. Deregulation of predominantly autosomal genes was observed, including TCL1A overexpression in 45,X B-lymphocytes and other known genes associated with hematological malignancies, prompting long-term personalized hemato-oncological surveillance in the reported patient.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-21T10:33:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005698","title":"Somatic pathogenic variants in the normal mammary gland of sporadic breast cancer patients.","description":"The mammary gland undergoes hormonally stimulated cycles of proliferation, lactation and involution. We hypothesized that these factors increase the mutational burden in glandular tissue and may explain high cancer incidence rate in the general population and recurrent disease. Hence, we investigated the DNA sequence variants in the normal mammary gland, tumor and peripheral blood from 52 reportedly sporadic breast cancer patients, including breast-conserving surgery cases. Targeted resequencing of 542 cancer associated genes revealed mosaic somatic pathogenic variants of: PIK3CA, TP53, AKT1, MAP3K1, CDH1, RB1, NCOR1, MED12, CBFB, TBX3 and TSHR in the normal mammary gland, at considerable allelic frequencies (9x10-2 to 5.2x10-1) indicating clonal expansion. Further evaluation of the frequently damaged PIK3CA and TP53 genes by ultra-sensitive duplex sequencing demonstrated a diversified picture of multiple low level-mosaic (in 10-2 to 10-4 alleles) hotspot pathogenic variants. Our results raise a question about the oncogenic potential in non-tumor mammary gland tissue of breast-conserving surgery patients.","abstract":"The mammary gland undergoes hormonally stimulated cycles of proliferation, lactation and involution. We hypothesized that these factors increase the mutational burden in glandular tissue and may explain high cancer incidence rate in the general population and recurrent disease. Hence, we investigated the DNA sequence variants in the normal mammary gland, tumor and peripheral blood from 52 reportedly sporadic breast cancer patients, including breast-conserving surgery cases. Targeted resequencing of 542 cancer associated genes revealed mosaic somatic pathogenic variants of: PIK3CA, TP53, AKT1, MAP3K1, CDH1, RB1, NCOR1, MED12, CBFB, TBX3 and TSHR in the normal mammary gland, at considerable allelic frequencies (9x10-2 to 5.2x10-1) indicating clonal expansion. Further evaluation of the frequently damaged PIK3CA and TP53 genes by ultra-sensitive duplex sequencing demonstrated a diversified picture of multiple low level-mosaic (in 10-2 to 10-4 alleles) hotspot pathogenic variants. Our results raise a question about the oncogenic potential in non-tumor mammary gland tissue of breast-conserving surgery patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-21T12:27:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005699","title":"High_throughput_scRNAseq","description":"The goal of this project is to setup, develop and evaluate ultra-high throughput single cell platforms and methodologies.  After establishing and developing these approaches e.g. chromium X, Sci-fi RNA seq, they will be tested on a wide range of applications e.g. single cell QTL mapping and single cell CRISPR screens.","abstract":"The goal of this project is to setup, develop and evaluate ultra-high throughput single cell platforms and methodologies.  After establishing and developing these approaches e.g. chromium X, Sci-fi RNA seq, they will be tested on a wide range of applications e.g. single cell QTL mapping and single cell CRISPR screens.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005700","title":"Genomic profile of sporadic multiple meningiomas","description":"Molecular mechanisms underlying the formation of sporadic MMs and clonal formation etiology of these tumors are poorly understood. \nIn this study, we worked on a cohort of patients with spatially separated MMs without prior radiation exposure or a family history who underwent surgical resection of at least two meningiomas. Unbiased, comprehensive next generation sequencing was performed and relevant clinical data was analyzed. \n We identified that both NF2-loss and non-NF2 driven MMs can form due to monoclonal expansion and those tumors can acquire inter-tumoral heterogeneity through branched evolution. Grade I and II meningiomas can occur in the same patient. Thus, the molecular make-up and clinical behavior of one tumor in MMs, cannot reliably lend insight into that of the others and suggests the clinical management strategy for MMs should be tailored individually.","abstract":"Molecular mechanisms underlying the formation of sporadic MMs and clonal formation etiology of these tumors are poorly understood. \nIn this study, we worked on a cohort of patients with spatially separated MMs without prior radiation exposure or a family history who underwent surgical resection of at least two meningiomas. Unbiased, comprehensive next generation sequencing was performed and relevant clinical data was analyzed. \n We identified that both NF2-loss and non-NF2 driven MMs can form due to monoclonal expansion and those tumors can acquire inter-tumoral heterogeneity through branched evolution. Grade I and II meningiomas can occur in the same patient. Thus, the molecular make-up and clinical behavior of one tumor in MMs, cannot reliably lend insight into that of the others and suggests the clinical management strategy for MMs should be tailored individually.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-21T18:14:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005701","title":"Gene expression profiling of SLE and healthy control samples","description":"mRNA-sequencing study of 141 patients with SLE and 48 healthy control samples.","abstract":"mRNA-sequencing study of 141 patients with SLE and 48 healthy control samples.","study_type":"Other","pubmed_ids":[35906002],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005702","title":"Human genomic and phenotypic synthetic data for the study of rare diseases","description":"The purpose of this dataset is to facilitate development of technical implementations for rare disease data integration, analysis, discovery,  and federated access.\n\nThis synthetic dataset includes clinical and genomic data from 6 rare disease cases. It consists of 18 whole genomes (6 index cases with their parents) which have genetic background based on public human data sequenced in the context of the Illumina Platinum initiative (Eberle, MA et al. (2017)) and made available by the HapMap project (https://www.genome.gov/10001688/international-hapmap-project). In each of the cases, real causative variants correlating with the phenotypic data provided were spiked-in.\n\nThe cases included in this synthetic dataset correspond to the following type of disorders:\nCASE 1- Congenital myasthenic syndrome (Autosomal Dominant -de novo variant)\nCASE 2- Macular dystrophy (Autosomal Dominant)\nCASE 3- Muscular dystrophy (Autosomal Recessive-compound heterozygous variants)\nCASE 4- Mitochondrial disorder (Autosomal Recessive-consanguineous case - homozygous variant)\nCASE 5- Breast cancer (Autosomal Dominant)\nCASE 6- Similar as case 1 for patient matchmaking tests: Congenital myasthenic syndrome (Autosomal Dominant-de novo variant)\n\nFor each case you will be able to download the following data: clinical information (phenopackets per individual and pedigree per family), raw genomic data (FASTQ and BAMs) and processed genomic data (vcfs).\n\nWhen using the data, the following should be acknowledged: the RD-Connect GPAP (https://platform.rd-connect.eu/), EC H2020 project EJP-RD (grant # 825575), EC H2020 project B1MG (grant # 951724) and Generalitat de Catalunya VEIS project (grant # 001-P-001647).","abstract":"The purpose of this dataset is to facilitate development of technical implementations for rare disease data integration, analysis, discovery,  and federated access.\n\nThis synthetic dataset includes clinical and genomic data from 6 rare disease cases. It consists of 18 whole genomes (6 index cases with their parents) which have genetic background based on public human data sequenced in the context of the Illumina Platinum initiative (Eberle, MA et al. (2017)) and made available by the HapMap project (https://www.genome.gov/10001688/international-hapmap-project). In each of the cases, real causative variants correlating with the phenotypic data provided were spiked-in.\n\nThe cases included in this synthetic dataset correspond to the following type of disorders:\nCASE 1- Congenital myasthenic syndrome (Autosomal Dominant -de novo variant)\nCASE 2- Macular dystrophy (Autosomal Dominant)\nCASE 3- Muscular dystrophy (Autosomal Recessive-compound heterozygous variants)\nCASE 4- Mitochondrial disorder (Autosomal Recessive-consanguineous case - homozygous variant)\nCASE 5- Breast cancer (Autosomal Dominant)\nCASE 6- Similar as case 1 for patient matchmaking tests: Congenital myasthenic syndrome (Autosomal Dominant-de novo variant)\n\nFor each case you will be able to download the following data: clinical information (phenopackets per individual and pedigree per family), raw genomic data (FASTQ and BAMs) and processed genomic data (vcfs).\n\nWhen using the data, the following should be acknowledged: the RD-Connect GPAP (https://platform.rd-connect.eu/), EC H2020 project EJP-RD (grant # 825575), EC H2020 project B1MG (grant # 951724) and Generalitat de Catalunya VEIS project (grant # 001-P-001647).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-22T14:08:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005703","title":"Pan_tissue_RNAseq","description":"he current RNA sequencing study is being performed in response to reviewers comments following submission to Nature. Reviewers are keen for authors to shed light on the underlying molecular mechanisms as to why synergy occurs between CHEK1i and TOP1i in MSS colorectal cancer. Two cell lines have been treated with each drug, as single agents and as a combination.","abstract":"Combinations of anti-cancer drugs can overcome resistance and provide new treatments for patients. The number of possible drug combinations vastly exceeds what could be tested clinically. Systematic efforts to identify active combinations, and the cancer types and molecular contexts in which they are most effective, could accelerate the development of combination treatments. Here, we evaluate the potency and efficacy of 2,025 clinically relevant two-drug combinations, generating the largest combination dataset in 128 molecularly-characterised breast, colorectal and pancreatic cancer cell lines. We show that synergy between drugs is rare and highly context dependent, and that combinations of targeted agents are most likely to be synergistic. We incorporate multi-omic molecular features to identify combination biomarkers and specify synergistic drug combinations and their active context, including combinations in the setting of basal-like breast cancer, microsatellite stable or KRAS mutant colon cancer. Our results show that irinotecan plus CHEK1 inhibition is synergistic in colon cancer cells, and that this combination leads to apoptosis and suppression of tumour xenograft growth. This study identifies clinically-relevant effective drug combinations in distinct molecular subpopulations and is a resource to guide rational efforts to prioritise development of combinatorial drug treatments.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005704","title":"BARIA baseline first 100 individuals transcriptomes","description":"Prevalence of obesity and associated diseases, including type 2 diabetes mellitus, dyslipidaemia and non-alcoholic fatty liver disease (NAFLD), are increasing. Underlying mechanisms, especially in humans, are unclear. Bariatric surgery provides the unique opportunity to obtain biopsies and portal vein blood-samples.\n\nMethods\nThe BARIA Study aims to assess how microbiota and their metabolites affect transcription in key tissues and clinical outcome in obese subjects and how baseline anthropometric and metabolic characteristics determine weight loss and glucose homeostasis after bariatric surgery. We phenotype patients undergoing bariatric surgery (predominantly laparoscopic Roux-en-Y gastric bypass), before weight loss, with biometrics, dietary and psychological questionnaires, mixed meal test (MMT) and collect fecal-samples and intra-operative biopsies from liver, adipose tissues and jejunum. We aim to include 1500 patients. A subset (approximately 25%) will undergo intra-operative portal vein blood-sampling. Fecal-samples are analyzed with shotgun metagenomics and targeted metabolomics, fasted and postprandial plasma-samples are subjected to metabolomics, and RNA is extracted from the tissues for RNAseq-analyses. Data will be integrated using state-of-the-art neuronal networks and metabolic modeling. Patient follow-up will be ten years.","abstract":"Prevalence of obesity and associated diseases, including type 2 diabetes mellitus, dyslipidaemia and non-alcoholic fatty liver disease (NAFLD), are increasing. Underlying mechanisms, especially in humans, are unclear. Bariatric surgery provides the unique opportunity to obtain biopsies and portal vein blood-samples.\n\nMethods\nThe BARIA Study aims to assess how microbiota and their metabolites affect transcription in key tissues and clinical outcome in obese subjects and how baseline anthropometric and metabolic characteristics determine weight loss and glucose homeostasis after bariatric surgery. We phenotype patients undergoing bariatric surgery (predominantly laparoscopic Roux-en-Y gastric bypass), before weight loss, with biometrics, dietary and psychological questionnaires, mixed meal test (MMT) and collect fecal-samples and intra-operative biopsies from liver, adipose tissues and jejunum. We aim to include 1500 patients. A subset (approximately 25%) will undergo intra-operative portal vein blood-sampling. Fecal-samples are analyzed with shotgun metagenomics and targeted metabolomics, fasted and postprandial plasma-samples are subjected to metabolomics, and RNA is extracted from the tissues for RNAseq-analyses. Data will be integrated using state-of-the-art neuronal networks and metabolic modeling. Patient follow-up will be ten years.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-25T12:56:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005705","title":"Characterization of Leukemic Stem Cells in DNMT3Amut and NPM1mut AMLs","description":null,"abstract":"Using a novel sorting strategy, we performed ultra low input RNAseq from FACS-sorted  populations from diagnostic DNMT3Amut and NPM1mut AML patients. Primary samples were retrospectively collected based on their mutational profile. Samples were thawed, stained and FACS sorted using combination of Lineage markers, CD34, GPR56 and NKG2DLigands. RNA was extracted and library prepared.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005706","title":"JAK1_NG_CBEABE_201021","description":"DNA has already been extracted.\n24 samples from genomic DNA\nCRISPR PCR1 and PCR2 indexing - Please use standard Kozuke primers.","abstract":"DNA has already been extracted.\n24 samples from genomic DNA\nCRISPR PCR1 and PCR2 indexing - Please use standard Kozuke primers.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005707","title":"Tiling_Base_editing_library","description":"QC for CRISPR base editing library to verify if the library design is fine.","abstract":"QC for CRISPR base editing library to verify if the library design is fine.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005708","title":"Characterising_the_small_RNA_profile_of_circulating_EVs_RNAseq","description":"This project will characterise the small RNA profile of circulating extracellular vesicles (EV) isolated from melanoma patients with the aim of establishing their utility as predictive biomarker reservoirs. Specifically, prior to treatment patients with metastatic disease will be recruited to a pilot study and blood collected for EV isolation with subsequent samples collected 3- and 12-months post-treatment. EVs will be isolated from blood plasma, RNA purified, and small RNA-sequencing carried out. Bioinformatic analysis will be performed in collaboration with Bart's and the London Genome Centre to identify changes in EV small RNA profiles across patients in response to treatment.","abstract":"This project will characterise the small RNA profile of circulating extracellular vesicles (EV) isolated from melanoma patients with the aim of establishing their utility as predictive biomarker reservoirs. Specifically, prior to treatment patients with metastatic disease will be recruited to a pilot study and blood collected for EV isolation with subsequent samples collected 3- and 12-months post-treatment. EVs will be isolated from blood plasma, RNA purified, and small RNA-sequencing carried out. Bioinformatic analysis will be performed in collaboration with Bart's and the London Genome Centre to identify changes in EV small RNA profiles across patients in response to treatment.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005709","title":"Combination_Immune_Checkpoint_Inhibition_in_Australian_Rare_Cancers_WES","description":"Combination immune checkpoint inhibition (ICI) with anti-CTLA-4 and anti-PD-1 blockade has demonstrated significant clinical activity across tumour types. Rare cancer patients have limited treatment options due to the scarcity of studies of novel treatment options, so they are often offered chemotherapies untested in their disease.  ONJ2016-001/CA209-538 is a prospective, multicentre clinical trial of combination ICI (ipilimumab and nivolumab) in patients with advanced rare cancers, including biliary tract, adrenocortical, rare gynaecological and neuroendocrine cancers (https://clinicaltrials.gov/ct2/show/NCT02923934). The primary endpoint is clinical benefit rate (complete response + partial response + stable disease &gt;3 months) by RECIST 1.1. This study involves generation and analysis of pre-treatment formalin fixed paraffin embedded (FFPE) tumour DNA sequencing data, paired with germline DNA sequencing data, to potentially identify genomic biomarkers that may associate with clinical benefit or other clinical efficacy / toxicity metrics.","abstract":"Combination immune checkpoint inhibition (ICI) with anti-CTLA-4 and anti-PD-1 blockade has demonstrated significant clinical activity across tumour types. Rare cancer patients have limited treatment options due to the scarcity of studies of novel treatment options, so they are often offered chemotherapies untested in their disease.  ONJ2016-001/CA209-538 is a prospective, multicentre clinical trial of combination ICI (ipilimumab and nivolumab) in patients with advanced rare cancers, including biliary tract, adrenocortical, rare gynaecological and neuroendocrine cancers (https://clinicaltrials.gov/ct2/show/NCT02923934). The primary endpoint is clinical benefit rate (complete response + partial response + stable disease &gt;3 months) by RECIST 1.1. This study involves generation and analysis of pre-treatment formalin fixed paraffin embedded (FFPE) tumour DNA sequencing data, paired with germline DNA sequencing data, to potentially identify genomic biomarkers that may associate with clinical benefit or other clinical efficacy / toxicity metrics.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-26T10:28:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005710","title":"DERMATLAS__Angioleiomyoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are angioleimyomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are angioleimyomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-26T10:36:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005711","title":"DERMATLAS__Angioleiomyoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are angioleiomyomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are angioleiomyomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-26T10:47:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005712","title":"DERMATLAS__Glomus_tumour_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are glomus tumours.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are glomus tumours.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-26T11:01:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005713","title":"DERMATLAS__Glomus_tumour_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are glomus tumours.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are glomus tumours.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-26T11:10:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005714","title":"DERMATLAS__Hidradenoma_papilliferum_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are hidradenoma papilliferums.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are hidradenoma papilliferums.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-26T11:17:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005715","title":"DERMATLAS__Hidradenoma_papilliferum_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are hidradenoma papilliferums.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are hidradenoma papilliferums.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-26T11:25:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005716","title":"DERMATLAS__Pilomatricoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are pilomatricomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are pilomatricomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005717","title":"DERMATLAS__Pilomatricoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are pilomatricomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are pilomatricomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005718","title":"DERMATLAS__Plexiform_fibrohistiocytic_tumour_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are plexiform fibrohistiocytic tumours.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are plexiform fibrohistiocytic tumours.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005719","title":"DERMATLAS__Plexiform_fibrohistiocytic_tumour_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are plexiform fibrohistiocytic tumours.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are plexiform fibrohistiocytic tumours.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005720","title":"DERMATLAS__Porocarcinoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are porocarcinomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are porocarcinomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-26T12:19:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005721","title":"DERMATLAS__Porocarcinoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are porocarcinomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are porocarcinomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-26T12:26:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005722","title":"DERMATLAS__Trichilemomma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are trichilemommas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are trichilemommas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005723","title":"DERMATLAS__Trichilemomma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are trichilemommas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are trichilemommas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005724","title":"DERMATLAS__Trichilemmal_carcinoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are trichilemmal carcinomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are trichilemmal carcinomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005725","title":"DERMATLAS__Trichilemmal_carcinoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible.\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are trichilemmal carcinomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible.\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are trichilemmal carcinomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005726","title":"DERMATLAS__Squamoid_eccrine_ductal_carcinoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are squamoid eccrine ductal carcinomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are squamoid eccrine ductal carcinomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005727","title":"DERMATLAS__Squamoid_eccrine_ductal_carcinoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible.\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are squamoid eccrine ductal carcinomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible.\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are squamoid eccrine ductal carcinomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005728","title":"RNAseq_of_healthy_mesothelial_cells_and_primary_mesothelioma_cell_lines","description":"Mesothelioma is a rare and aggressive cancer associated with previous exposure to asbestos. Currently there are no effective treatments for mesothelioma and majority of patients will die within a year after diagnosis. Although a large number of preclinical and clinical trials assessed the efficacy of various therapuetic modes, including anti-angiogenic therapies, immunotherapy, antibody-drug conjugates and oncolytic viruses, none of the tested molecules entered the clinic. Thus, to better understand what drives mesothelioma carcinogenesis and to identify novel targets for therapy, in this project we aim at performing a comprehensive transcriptomic analysis of heathy mesothelial cells and a panel of mesothelioma cells lines. Primary mesothelial cell lines were established in prof. Marciniak lab from human pleural specimens, while primary mesothelioma cell lines were obtained from MesobanK. Both models constitute low passage cell lines and therefore should closely represent genetics of the original tissue.","abstract":"Mesothelioma is a rare and aggressive cancer associated with previous exposure to asbestos. Currently there are no effective treatments for mesothelioma and majority of patients will die within a year after diagnosis. Although a large number of preclinical and clinical trials assessed the efficacy of various therapuetic modes, including anti-angiogenic therapies, immunotherapy, antibody-drug conjugates and oncolytic viruses, none of the tested molecules entered the clinic. Thus, to better understand what drives mesothelioma carcinogenesis and to identify novel targets for therapy, in this project we aim at performing a comprehensive transcriptomic analysis of heathy mesothelial cells and a panel of mesothelioma cells lines. Primary mesothelial cell lines were established in prof. Marciniak lab from human pleural specimens, while primary mesothelioma cell lines were obtained from MesobanK. Both models constitute low passage cell lines and therefore should closely represent genetics of the original tissue.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-26T16:12:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005729","title":"Barrett esophagus phenotypic evolution study","description":null,"abstract":"Barrett esophagus (BE) is a risk factor for the development of esophageal adenocarcinoma, however our understanding of how Barrett esophagus evolves is still poorly understood. We demonstrate that dynamic clonal phenotypic changes occur at the gland level, the mechanism by which these changes evolve, and how diversity may play a role in progression. We analyzed the distribution and diversity of gland phenotype between and within BE biopsies and the background mucosa of those that had progressed to dysplasia or developed BE post-esophagectomy, using immunohistochemistry and H&amp;E analysis. Clonal relationships between distinct gland types were determined by laser capture microdissection sequencing of the mitochondrial genome. Five different non-dysplastic gland phenotypes were identified in a cohort of 64 patients biopsies taken at the same physical location in the esophagus; most non-dysplastic patients showed a single gland phenotype per biopsy, but some showed two or three gland types. We reveal a shared common ancestor between parietal cell-containing oxynto-cardiac glands and goblet cell-containing specialized Barrett glands through a shared somatic mtDNA mutation. We also reveal a similar relationship between specialized and cardiac-type glands, and specialized and Paneth cell-containing glands. The diversity of gland types was significantly increased adjacent to dysplasia compared to non-dysplastic BE and patients with post-esophagectomy BE, suggesting that gland diversity evolves in BE patients over time.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-26T19:09:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005730","title":"Human and rat skeletal muscle multi-omic profiling","description":"Skeletal muscle accounts for the largest proportion of human body mass, on average, and is a key tissue in complex diseases and mobility. It is composed of several different cell and muscle fiber types. Here, we optimize single-nucleus ATAC-seq (snATAC-seq) to map skeletal muscle cell-specific chromatin accessibility landscapes in frozen human and rat samples, and single-nucleus RNA-seq (snRNA-seq) to map cell-specific transcriptomes in human. We additionally perform multi-omics profiling (gene expression and chromatin accessibility) on human and rat muscle samples.","abstract":"Skeletal muscle accounts for the largest proportion of human body mass, on average, and is a key tissue in complex diseases and mobility. It is composed of several different cell and muscle fiber types. Here, we optimize single-nucleus ATAC-seq (snATAC-seq) to map skeletal muscle cell-specific chromatin accessibility landscapes in frozen human and rat samples, and single-nucleus RNA-seq (snRNA-seq) to map cell-specific transcriptomes in human. We additionally perform multi-omics profiling (gene expression and chromatin accessibility) on human and rat muscle samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-26T21:59:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005731","title":"DNA methylation and Panel sequencing for pancreatic neuroendocrine carcinomas (PanNECs) and pancreatic neuroendocrine tumors (PanNETs)","description":null,"abstract":"Pancreatic Neuroendocrine Neoplasms (PanNENs) are two subclasses: the well-differentiated, low to high-grade Pancreatic Neuroendocrine Tumors (PanNETs) and the poorly-differentiated, high-grade Pancreatic Neuroendocrine Carcinomas (PanNECs). DNA methylation and sequencing was performed for 57 PanNEN samples to decipher distinct methylation profiles separating PanNENs. Our study provides a robust and clinically applicable method to clearly distinguish PanNECs from PanNETG3s and improve patient stratification.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-26T23:34:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005732","title":"scRNA-seq of LN and lymphoma stroma","description":"The activities of non-haematopoietic cells (NHCs), including mesenchymal stromal cells and endothelial cells, in lymphomas, reportedly underlie lymphomagenesis. However, understanding of lymphoma NHCs has been hampered by unexplained NHC heterogeneity, even in normal human lymph nodes (LNs). Here, we constructed a single-cell transcriptome atlas of &gt;100,000 NHCs collected from 27 human samples, including LNs and various nodal lymphomas, revealing 30 distinct subclusters, including some that were previously unrecognized. Notably, this atlas was highly useful for comparative analysis with lymphoma NHCs, which revealed an unanticipated landscape of subcluster-specific changes in gene expression and interaction with malignant cells in follicular lymphoma NHCs, facilitating our understanding of stromal remodelling in lymphoma and potentially suggesting novel biomarkers. Our study largely updates NHC taxonomy in human LNs and pertains to analysis of disease status, providing a rich resource and deeper insights into LN and lymphoma biology and offering to advance lymphoma management and therapy.","abstract":"The activities of non-haematopoietic cells (NHCs), including mesenchymal stromal cells and endothelial cells, in lymphomas, reportedly underlie lymphomagenesis. However, understanding of lymphoma NHCs has been hampered by unexplained NHC heterogeneity, even in normal human lymph nodes (LNs). Here, we constructed a single-cell transcriptome atlas of &gt;100,000 NHCs collected from 27 human samples, including LNs and various nodal lymphomas, revealing 30 distinct subclusters, including some that were previously unrecognized. Notably, this atlas was highly useful for comparative analysis with lymphoma NHCs, which revealed an unanticipated landscape of subcluster-specific changes in gene expression and interaction with malignant cells in follicular lymphoma NHCs, facilitating our understanding of stromal remodelling in lymphoma and potentially suggesting novel biomarkers. Our study largely updates NHC taxonomy in human LNs and pertains to analysis of disease status, providing a rich resource and deeper insights into LN and lymphoma biology and offering to advance lymphoma management and therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-27T13:17:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005733","title":"RCC Xenografts EuroTARGET","description":null,"abstract":"Comparative analysis of renal cell carcinoma cell lines and corresponding xenografts with and without sunitinib treatment.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005734","title":"Molecular_risk_stratification_in_patients_with_T1_colorectal_cancer_WES","description":"The introduction of bowel cancer screening has led to a significant increase in the proportion of patients being diagnosed with asymptomatic, early-stage colorectal cancer (CRC). Although the majority of these patients are successfully treated with surgery alone, a small proportion of patients have ‘born-to-be-bad’ aggressive lesions with early dissemination leading to distant metastases. Current standard of care histological assessment is unable to distinguish between these aggressive versus non-aggressive early lesions which is essential to provide appropriate clinical management decisions. This study aims to carry out molecular and histological profiling of approximately 300 T1 CRCs in order to develop a molecular stratifier based on the risk of relapse in early-invasive CRC. This novel T1 cohort will represent the world’s largest molecularly characterised T1 cohort of samples, with digital pathology assessment alongside whole exome sequencing, copy number variation analysis and 3’ RNA-seq. This data will be used to generate a robust panel of molecular and/or histological markers applicable to formalin-fixed paraffin embedded (FFPE) archival tissue which discriminates between T1 lesions based on risk of relapse, which will ultimately be used to inform clinical management of CRC at the earliest stages of the disease.","abstract":"The introduction of bowel cancer screening has led to a significant increase in the proportion of patients being diagnosed with asymptomatic, early-stage colorectal cancer (CRC). Although the majority of these patients are successfully treated with surgery alone, a small proportion of patients have ‘born-to-be-bad’ aggressive lesions with early dissemination leading to distant metastases. Current standard of care histological assessment is unable to distinguish between these aggressive versus non-aggressive early lesions which is essential to provide appropriate clinical management decisions. This study aims to carry out molecular and histological profiling of approximately 300 T1 CRCs in order to develop a molecular stratifier based on the risk of relapse in early-invasive CRC. This novel T1 cohort will represent the world’s largest molecularly characterised T1 cohort of samples, with digital pathology assessment alongside whole exome sequencing, copy number variation analysis and 3’ RNA-seq. This data will be used to generate a robust panel of molecular and/or histological markers applicable to formalin-fixed paraffin embedded (FFPE) archival tissue which discriminates between T1 lesions based on risk of relapse, which will ultimately be used to inform clinical management of CRC at the earliest stages of the disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-28T15:53:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005735","title":"Unifying recovery dynamics in heterogeneous diseases exemplified by COVID-19","description":"Studying the recovery dynamics in different diseases poses many difficulties, as patients often display high heterogeneity in their recovery courses. Moreover, most attempts to study disease dynamics focus on disease progression rather than disease recovery mechanisms. To model recovery dynamics, using severe COVID-19 as the example, we align heterogeneous recovery trajectories via a novel computational scheme applied to longitudinally sampled blood transcriptomes. We thus generate pseudotime trajectories, which we then link to cellular and molecular mechanisms based on cell deconvolution analysis and molecular pathway prediction, thus presenting a unique framework for studying recovery processes over time. Specifically, mature neutrophils displayed a gradual decrease during recovery, allowing superior useability for outcome prediction compared to currently used clinical markers. Further, we discovered a recovery-related regulatory change in gene programs resulting in immune rebalancing between interferon and NFkB activity and the restoration of cell homeostasis. We thus propose regulatory mechanisms governing COVID-19 recovery and suggest mature neutrophils and additional gene markers, as novel clinical biomarkers for disease outcome. Overall, we present a novel clinically relevant computational framework for modeling disease recovery, paving the way for future studies of the recovery dynamics in other diseases and tissues.","abstract":"Studying the recovery dynamics in different diseases poses many difficulties, as patients often display high heterogeneity in their recovery courses. Moreover, most attempts to study disease dynamics focus on disease progression rather than disease recovery mechanisms. To model recovery dynamics, using severe COVID-19 as the example, we align heterogeneous recovery trajectories via a novel computational scheme applied to longitudinally sampled blood transcriptomes. We thus generate pseudotime trajectories, which we then link to cellular and molecular mechanisms based on cell deconvolution analysis and molecular pathway prediction, thus presenting a unique framework for studying recovery processes over time. Specifically, mature neutrophils displayed a gradual decrease during recovery, allowing superior useability for outcome prediction compared to currently used clinical markers. Further, we discovered a recovery-related regulatory change in gene programs resulting in immune rebalancing between interferon and NFkB activity and the restoration of cell homeostasis. We thus propose regulatory mechanisms governing COVID-19 recovery and suggest mature neutrophils and additional gene markers, as novel clinical biomarkers for disease outcome. Overall, we present a novel clinically relevant computational framework for modeling disease recovery, paving the way for future studies of the recovery dynamics in other diseases and tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-28T18:28:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005736","title":"Mult-omics Palbociclib Resistance Study in HR+/HER2– Metastatic Breast Cancer","description":"Resistance to CDK4/6 inhibitors and endocrine therapy (ET) are common and poorly understood since they have been real game changer in patients with HR-positive and HER2-negative MBC. A comprehensive genomic and transcriptomic analysis of pre-treatment and post-treatment tumors from patients treated with palbociclib plus ET identified novel markers associated with poor prognosis such as genomic scar features caused by homologous repair deficiency (HRD), estrogen response signatures, and four unique prognostic clusters with distinct molecular features. Tumors with TP53 mutations co-occurring with a unique HRD-high cluster responded poorly. By comparing genomic and transciptomic profiles of paired samples, tumors were found to be further enriched in HRD genomic scars and many had switched to aggressive molecular subtypes. Furthermore, we identified high frequencies of acquired genomic alterations upon disease progression in RB1, ESR1, PTEN, and KMT2C. Our findings provide new insight into potential predictive biomarkers that could be targeted to overcome resistance. (NCT03401359)","abstract":"Resistance to CDK4/6 inhibitors and endocrine therapy (ET) are common and poorly understood since they have been real game changer in patients with HR-positive and HER2-negative MBC. A comprehensive genomic and transcriptomic analysis of pre-treatment and post-treatment tumors from patients treated with palbociclib plus ET identified novel markers associated with poor prognosis such as genomic scar features caused by homologous repair deficiency (HRD), estrogen response signatures, and four unique prognostic clusters with distinct molecular features. Tumors with TP53 mutations co-occurring with a unique HRD-high cluster responded poorly. By comparing genomic and transciptomic profiles of paired samples, tumors were found to be further enriched in HRD genomic scars and many had switched to aggressive molecular subtypes. Furthermore, we identified high frequencies of acquired genomic alterations upon disease progression in RB1, ESR1, PTEN, and KMT2C. Our findings provide new insight into potential predictive biomarkers that could be targeted to overcome resistance. (NCT03401359)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-29T08:51:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005737","title":"Genetic variability in exon 1 of the glucocorticoid receptor gene NR3C1 is associated with postoperative complications","description":"Patients having major surgery experience inflammation post-operatively, which may contribute to post-operative morbidity. Endogenous glucocorticoids (GCs) are an essential part of the stress response, but this response varies between individuals, which may in turn affect clinical outcome in general, and post-operative inflammation, specifically. Exon 1 of the NR3C1 gene, encoding the glucocorticoid receptor, contains an established region of differential regulation. DNA methylation patterns in this region have been found to differ between individuals. We investigated the methylation status and genotype in the Cytosine-phosphate-Guanine (CpG) island in exon 1 of NR3C1 in 24 patients who underwent major abdominal surgery and correlated it with post-operative complications. DNA was extracted from peripheral blood leukocytes and underwent targeted bisulfite sequencing of the CpG island. Complications were graded according to the Clavien-Dindo classification and 14 out of 24 had post-operative complications.  Multifactorial and partial least square methods were used to analyse the data.  A homogenous demethylated pattern was observed in all patients and no single CpG methylation was associated with post-operative complications. Four single nucleotide polymorphisms (SNPs) were significantly correlated with higher Clavien-Dindo scores. Genetic variability in the chr5:143,402,505-143,405,805 region of exon 1 of the glucocorticoid receptor gene NR3C1, but not DNA methylation, was associated with more severe post-operative complications in patients having major abdominal surgery. This indicates that the response to GCs may be of clinical importance for inflammatory conditions.","abstract":"Patients having major surgery experience inflammation post-operatively, which may contribute to post-operative morbidity. Endogenous glucocorticoids (GCs) are an essential part of the stress response, but this response varies between individuals, which may in turn affect clinical outcome in general, and post-operative inflammation, specifically. Exon 1 of the NR3C1 gene, encoding the glucocorticoid receptor, contains an established region of differential regulation. DNA methylation patterns in this region have been found to differ between individuals. We investigated the methylation status and genotype in the Cytosine-phosphate-Guanine (CpG) island in exon 1 of NR3C1 in 24 patients who underwent major abdominal surgery and correlated it with post-operative complications. DNA was extracted from peripheral blood leukocytes and underwent targeted bisulfite sequencing of the CpG island. Complications were graded according to the Clavien-Dindo classification and 14 out of 24 had post-operative complications.  Multifactorial and partial least square methods were used to analyse the data.  A homogenous demethylated pattern was observed in all patients and no single CpG methylation was associated with post-operative complications. Four single nucleotide polymorphisms (SNPs) were significantly correlated with higher Clavien-Dindo scores. Genetic variability in the chr5:143,402,505-143,405,805 region of exon 1 of the glucocorticoid receptor gene NR3C1, but not DNA methylation, was associated with more severe post-operative complications in patients having major abdominal surgery. This indicates that the response to GCs may be of clinical importance for inflammatory conditions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-29T12:24:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005738","title":"Genome-wide cell-free DNA termini in patients with cancer","description":"The structure, fragmentation pattern, length and terminal sequence of cell-free DNA (cfDNA) is under the influence of nucleases present in the blood. We hypothesized that differences in the diversity of bases at the end of cfDNA fragments can be leveraged on a genome-wide scale to enhance the sensitivity for detecting the presence of tumor signals in plasma. We surveyed the cfDNA termini in 72 plasma samples from 319 patients with 18 different cancer types using low-coverage whole genome sequencing. The fragment-end sequence and diversity were altered in all cancer types in comparison to 76 healthy controls. We converted the fragment end sequences into a quantitative metric and observed that this correlates with circulating tumor DNA tumor fraction (R = 0.58, p &lt; 0.001, Spearman). Using these metrics, we were able to classify cancer samples from control at a low tumor content (AUROC of 91% at 1% tumor fraction) and shallow sequencing coverage (mean AUROC = 0.99 at &gt;1M fragments). Combining fragment-end sequences and diversity using machine learning, we classified cancer from healthy controls (mean AUROC = 0.99, SD = 0.01). Using unsupervised clustering we showed that early-stage lung cancer can be classified from control or later stages based on fragment-end sequences. We observed that fragment-end sequences can be used for prognostication (hazard ratio: 0.49) and residual disease detection inresectable esophageal adenocarcinoma patients, moving fragmentomics toward a greater\nclinical implementation.","abstract":"The structure, fragmentation pattern, length and terminal sequence of cell-free DNA (cfDNA) is under the influence of nucleases present in the blood. We hypothesized that differences in the diversity of bases at the end of cfDNA fragments can be leveraged on a genome-wide scale to enhance the sensitivity for detecting the presence of tumor signals in plasma. We surveyed the cfDNA termini in 72 plasma samples from 319 patients with 18 different cancer types using low-coverage whole genome sequencing. The fragment-end sequence and diversity were altered in all cancer types in comparison to 76 healthy controls. We converted the fragment end sequences into a quantitative metric and observed that this correlates with circulating tumor DNA tumor fraction (R = 0.58, p &lt; 0.001, Spearman). Using these metrics, we were able to classify cancer samples from control at a low tumor content (AUROC of 91% at 1% tumor fraction) and shallow sequencing coverage (mean AUROC = 0.99 at &gt;1M fragments). Combining fragment-end sequences and diversity using machine learning, we classified cancer from healthy controls (mean AUROC = 0.99, SD = 0.01). Using unsupervised clustering we showed that early-stage lung cancer can be classified from control or later stages based on fragment-end sequences. We observed that fragment-end sequences can be used for prognostication (hazard ratio: 0.49) and residual disease detection inresectable esophageal adenocarcinoma patients, moving fragmentomics toward a greater\nclinical implementation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-29T13:15:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005739","title":"cfDNA and CDX/PDX methylation profiling in SCLC","description":"We profiled the whole genome methylome of SCLC preclinical models and cfDNA samples. We assessed the sensitivity of cfDNA methylation profiling in detecting SCLC, especially at earlier stage of disease and the ability in discriminate among different SCLC molecular subtypes.","abstract":"We profiled the whole genome methylome of SCLC preclinical models and cfDNA samples. We assessed the sensitivity of cfDNA methylation profiling in detecting SCLC, especially at earlier stage of disease and the ability in discriminate among different SCLC molecular subtypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-29T13:56:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005740","title":"Whole transcriptome profiling of liquid biopsies from tumour xenografted mouse models enables specific monitoring of tumour-derived extracellular RNA","description":null,"abstract":"While cell-free DNA (cfDNA) in liquid biopsies is widely being used and investigated, free circulating RNA (extracellular RNA, exRNA) has the potential to improve therapy response monitoring and cancer detection due to its dynamic nature. A fundamental open question hampering the initiation of large-scale liquid biopsy collections for tumour exRNA analysis is that it remains unclear in which blood subcompartment tumour-derived exRNAs primarily reside. We set out to develop a host-xenograft deconvolution framework, exRNAxeno, with cDNA mapping strategies to either a combined human-mouse reference genome or both species genomes in parallel, that can be applied to exRNA sequencing data from liquid biopsies of human xenograft mouse models, enabling to distinguish (human) tumoural RNA from (murine) host RNA, and as such to specifically analyse tumour-derived exRNA. Subsequently, the preferred exRNAxeno combination pipeline was applied to total exRNA sequencing data from blood platelets and three plasma fractions from a breast cancer patient-derived and neuroblastoma cell line-derived xenograft mouse model. We show that tumoural exRNA concentrations are not determined by plasma platelet levels, while host exRNA concentrations increase with platelet content. Furthermore, a large variability in exRNA levels and gene content across individual mice is observed. In general, the tumoural gene detectability in plasma is correlated with the RNA expression levels in the tumour tissue or cancer cell line. Our results unravel new aspects of tumour-derived exRNA biology in xenograft mouse models.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-29T14:48:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005741","title":"Genomic_landscape_of_pre_malignant_and_malignant_lung_tissue_","description":"Sequencing of LCM-derived microbiopsies from one individual with smoking history and different lung pathologies, including normal, atypical pre-malignant and malignant tissues. Our goal is to assess the mutational burden, spectrum, and clonal dynamics within the tissues. Lung tissues from the proximal and distal airway, and pleura, which has been inflated using paxgene-fixation, will be analysed . Ultimately, we will sample at multiple sites to understand the relationship between the histological presentation and the genomic landscape, with the goal to understand drivers of the transition from normal to cancer.","abstract":"Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue of the lung. We aim to use laser-capture microscopy (LCM) to sample individual clones from lhealthy ung tissue as well as premalignant and atypical lesions to identify whether cancer-associated mutations appear in this transition, assess the mutational burden present, and identify the mutational processes causing these mutations. We will extensively sample from an individual whose lung lobe has been resected and inflated in paxgene. We will be comparing the premalignant tissues with properties of lung cancer to gain insight into the earliest stages of tumour development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005742","title":"Profiling_genomic_alterations_across_the_human_bronchial_tree","description":"This study aims to profile the bronchial epithelium along the lung tree of 10 patients with smoking history and eventually lung cancer. The biopsies have been resected upon radiology screening and detection of lung cancer. In frame of this, multiple biopsies from proximal and distal airway as well as the transitions have been samples and will be subject to whole-genome sequencing. This will enable us to investigate the somatic alterations shared by proximal and distal airways, i.e. the mutation burden, mutational signatures as well as copy number alterations and structural variation.","abstract":"The work implemented here aims to unravel the relationship between proximal and distal airway epithelium. Implicitly, we aim to characterize the mutation landscape of normal epithelium and the transition from proximal to distal airways in patients with various smoking histories and lung pathologies. The results from whole genome sequencing will be integrated with spatial transcriptomics profiling of histological sections from the identical sample. This will not only allow us to investigate the genomic alterations, but also enable the matching of spatial genomic information from laser-capture microdissections and transcriptomic features in normal epithelium with differences in their somatic mutations. Through this, we will increase our understanding of tissue heterogeneity and prospectively lung diseases including cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005743","title":"Comparative analysis of RAF depletion vs. MAPK inhibition","description":null,"abstract":"KRAS, mutated in ~30% of all cancers, activates the RAF-MEK-ERK signaling cascade.  CRAF is required for growth of KRAS mutant lung tumors, but the requirement for CRAF kinase activity is unknown. Here, we show subsets of KRAS mutant tumors are dependent on CRAF for growth. Kinase-dead but not dimer-defective CRAF rescued growth inhibition suggesting dimerization but not kinase activity is required.  Quantitative proteomics demonstrated enrichment of CRAF:ARAF dimers in KRAS mutant cells and depletion of both CRAF and ARAF rescued the CRAF loss phenotype.  Mechanistically, CRAF depletion caused sustained ERK activation and induction of cell cycle arrest, while treatment with low dose MEK or ERK inhibitor rescued the CRAF loss phenotype. Our studies highlight the role of CRAF in regulating MAPK signal intensity to promote tumorigenesis downstream of mutant KRAS and suggest disrupting CRAF dimerization or degrading CRAF may have therapeutic benefit.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-29T21:02:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005744","title":"IN UTERO ORIGIN OF MYELOFIBROSIS PRESENTING IN ADULT MONOZYGOTIC TWINS AFTER A PROLONGED DISEASE LATENCY","description":null,"abstract":"The latency between initiating somatic cancer driver mutation acquisition by a single cell and clinical presentation is largely unknown. We present a remarkable case of monozygotic twins presenting with CALR mutation-positive myeloproliferative neoplasms (MPNs) aged 37 and 38. Whole genome sequencing lineage-tracing revealed a common clonal origin of the CALR-mutant MPN clone, which occurred in utero followed by twin-to-twin transplacental transmission. Index sorting and single-colony genotyping revealed phenotypic hematopoietic stem cells (HSCs) as the likely MPN-propagating cell. This case provides a unique window into the prolonged evolutionary dynamics of MPNs and fitness advantage exerted by MPN-associated driver mutations in HSCs.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-29T23:02:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005745","title":"Stereotyped B-cell responses are linked to IgG constant region polymorphisms in multiple sclerosis","description":"Clonally related B cells infiltrate the brain, meninges, and cerebrospinal fluid of multiple sclerosis (MS) patients, but the mechanisms driving the B-cell response and shaping the immunoglobulin repertoires remain unclear. Here, we used single-cell full-length RNA-seq and B-cell receptor reconstruction to simultaneously assess the phenotypes, isotypes, constant region polymorphisms, and the paired heavy- and light-chain repertoires in intrathecal B cells. We detected extensive clonal connections between the memory B cell and antibody-secreting cell compartments and observed clonally related cells of different isotypes, including IgM/IgG1, IgG1/IgA1, IgG1/IgG2, and IgM/IgA1. There was a strong dominance of the G1m1 allotype constant region polymorphisms in antibody-secreting cells, but not in memory B cells. Tightly linked to the G1m1 allotype, we found a preferential pairing of the immunoglobulin heavy-chain variable (IGHV)4 gene family with the κ variable (IGKV)1 gene family. The IGHV4-39 gene was most used and showed the highest frequency of pairing with IGKV1-5 and IGKV1(D)-33. These results link IgG constant region polymorphisms to stereotyped B-cell responses in MS and indicate that the intrathecal B-cell response in these patients could be directed against structurally similar epitopes.","abstract":"Clonally related B cells infiltrate the brain, meninges, and cerebrospinal fluid of multiple sclerosis (MS) patients, but the mechanisms driving the B-cell response and shaping the immunoglobulin repertoires remain unclear. Here, we used single-cell full-length RNA-seq and B-cell receptor reconstruction to simultaneously assess the phenotypes, isotypes, constant region polymorphisms, and the paired heavy- and light-chain repertoires in intrathecal B cells. We detected extensive clonal connections between the memory B cell and antibody-secreting cell compartments and observed clonally related cells of different isotypes, including IgM/IgG1, IgG1/IgA1, IgG1/IgG2, and IgM/IgA1. There was a strong dominance of the G1m1 allotype constant region polymorphisms in antibody-secreting cells, but not in memory B cells. Tightly linked to the G1m1 allotype, we found a preferential pairing of the immunoglobulin heavy-chain variable (IGHV)4 gene family with the κ variable (IGKV)1 gene family. The IGHV4-39 gene was most used and showed the highest frequency of pairing with IGKV1-5 and IGKV1(D)-33. These results link IgG constant region polymorphisms to stereotyped B-cell responses in MS and indicate that the intrathecal B-cell response in these patients could be directed against structurally similar epitopes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-30T13:48:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005746","title":"Proteogenomics of chronic lymphocytic leukemia","description":"Cancer heterogeneity at the proteome level may explain differences in therapy response and prognosis beyond the currently established genomic and transcriptomic based diagnostics. The relevance of proteomics for disease classifications remains to be established in clinically heterogeneous cancer entities such as chronic lymphocytic leukemia (CLL). Here, we characterized the proteome and transcriptome in-depth alongside genetic and ex-vivo drug response profiling in a clinically well annotated CLL discovery cohort (n= 68). Unsupervised clustering of the proteome data revealed six subgroups. Five of these proteomic groups were associated with genetic features, while one group was only detectable at the proteome level. This new group was characterized by accelerated disease progression, high spliceosomal protein abundances associated with aberrant splicing, and low B cell receptor signaling protein abundances (ASB-CLL). We developed classifiers to identify ASB-CLL based on its characteristic proteome or splicing signature in two independent cohorts (n= 165, n= 169) and confirmed that ASB-CLL comprises about 20 % of CLL patients. The inferior overall survival observed in ASB-CLL was independent of both TP53- and IGHV mutation status. Our multi-omics analysis refines the classification of CLL and highlights the potential of proteomics to improve cancer patient stratification beyond genetic and transcriptomic profiling.  \nThis is the transcriptomics data of the discovery cohort.","abstract":"Cancer heterogeneity at the proteome level may explain differences in therapy response and prognosis beyond the currently established genomic and transcriptomic based diagnostics. The relevance of proteomics for disease classifications remains to be established in clinically heterogeneous cancer entities such as chronic lymphocytic leukemia (CLL). Here, we characterized the proteome and transcriptome in-depth alongside genetic and ex-vivo drug response profiling in a clinically well annotated CLL discovery cohort (n= 68). Unsupervised clustering of the proteome data revealed six subgroups. Five of these proteomic groups were associated with genetic features, while one group was only detectable at the proteome level. This new group was characterized by accelerated disease progression, high spliceosomal protein abundances associated with aberrant splicing, and low B cell receptor signaling protein abundances (ASB-CLL). We developed classifiers to identify ASB-CLL based on its characteristic proteome or splicing signature in two independent cohorts (n= 165, n= 169) and confirmed that ASB-CLL comprises about 20 % of CLL patients. The inferior overall survival observed in ASB-CLL was independent of both TP53- and IGHV mutation status. Our multi-omics analysis refines the classification of CLL and highlights the potential of proteomics to improve cancer patient stratification beyond genetic and transcriptomic profiling.  \nThis is the transcriptomics data of the discovery cohort.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-10-31T15:22:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005747","title":"Genome-wide cell-free DNA termini in patients with cancer","description":"The structure, fragmentation pattern, length and terminal sequence of cell-free DNA (cfDNA) is under the influence of nucleases present in the blood. We hypothesized that differences in the diversity of bases at the end of cfDNA fragments can be leveraged on a genome-wide scale to enhance the sensitivity for detecting the presence of tumor signals in plasma. We surveyed the cfDNA termini in 72 plasma samples from 319 patients with 18 different cancer types using low-coverage whole genome sequencing. The fragment-end sequence and diversity were altered in all cancer types in comparison to 76 healthy controls. We converted the fragment end sequences into a quantitative metric and observed that this correlates with circulating tumor DNA tumor fraction (R = 0.58, p &lt; 0.001, Spearman). Using these metrics, we were able to classify cancer samples from control at a low tumor content (AUROC of 91% at 1% tumor fraction) and shallow sequencing coverage (mean AUROC = 0.99 at &gt;1M fragments). Combining fragment-end sequences and diversity using machine learning, we classified cancer from healthy controls (mean AUROC = 0.99, SD = 0.01). Using unsupervised clustering we showed that early-stage lung cancer can be classified from control or later stages based on fragment-end sequences. We observed that fragment-end sequences can be used for prognostication (hazard ratio: 0.49) and residual disease detection inresectable esophageal adenocarcinoma patients, moving fragmentomics toward a greater\nclinical implementation.","abstract":"The structure, fragmentation pattern, length and terminal sequence of cell-free DNA (cfDNA) is under the influence of nucleases present in the blood. We hypothesized that differences in the diversity of bases at the end of cfDNA fragments can be leveraged on a genome-wide scale to enhance the sensitivity for detecting the presence of tumor signals in plasma. We surveyed the cfDNA termini in 72 plasma samples from 319 patients with 18 different cancer types using low-coverage whole genome sequencing. The fragment-end sequence and diversity were altered in all cancer types in comparison to 76 healthy controls. We converted the fragment end sequences into a quantitative metric and observed that this correlates with circulating tumor DNA tumor fraction (R = 0.58, p &lt; 0.001, Spearman). Using these metrics, we were able to classify cancer samples from control at a low tumor content (AUROC of 91% at 1% tumor fraction) and shallow sequencing coverage (mean AUROC = 0.99 at &gt;1M fragments). Combining fragment-end sequences and diversity using machine learning, we classified cancer from healthy controls (mean AUROC = 0.99, SD = 0.01). Using unsupervised clustering we showed that early-stage lung cancer can be classified from control or later stages based on fragment-end sequences. We observed that fragment-end sequences can be used for prognostication (hazard ratio: 0.49) and residual disease detection inresectable esophageal adenocarcinoma patients, moving fragmentomics toward a greater\nclinical implementation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-01T09:12:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005748","title":"The effect of pre-analytical and physiological variables on cell-free DNA fragmentation","description":"Background: assays that account for the biological properties and fragmentation of cell-free DNA (cfDNA) can improve the performance of liquid biopsy. However, pre-analytic and physiological differences between individuals on fragmentomic analysis are poorly defined.\nMethods: we analyzed the impact of collection tube, plasma processing time and physiology on the size distribution of cfDNA, their genome-wide representation and sequence diversity at the cfDNA fragment-ends using shallow Whole Genome Sequencing. \nResults: we observed that using different stabilizing collection tubes, or processing times does not affect the cfDNA fragment sizes, but can impact the genome-wide fragmentation patterns and fragment-end sequences of cfDNA. In addition, beyond differences depending on the gender, the physiological conditions tested between 63 individuals (age, body mass index, use of medication and chronic conditions) minimally influenced the outcome of fragmentomic methods.\nConclusions: our results highlight that fragmentomic approaches have potential for implementation in the clinic, pending clear traceability of analytical and physiological factors.","abstract":"Background: assays that account for the biological properties and fragmentation of cell-free DNA (cfDNA) can improve the performance of liquid biopsy. However, pre-analytic and physiological differences between individuals on fragmentomic analysis are poorly defined.\nMethods: we analyzed the impact of collection tube, plasma processing time and physiology on the size distribution of cfDNA, their genome-wide representation and sequence diversity at the cfDNA fragment-ends using shallow Whole Genome Sequencing. \nResults: we observed that using different stabilizing collection tubes, or processing times does not affect the cfDNA fragment sizes, but can impact the genome-wide fragmentation patterns and fragment-end sequences of cfDNA. In addition, beyond differences depending on the gender, the physiological conditions tested between 63 individuals (age, body mass index, use of medication and chronic conditions) minimally influenced the outcome of fragmentomic methods.\nConclusions: our results highlight that fragmentomic approaches have potential for implementation in the clinic, pending clear traceability of analytical and physiological factors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-01T09:12:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005749","title":"Gene expression profile of mesothelial cells from peritoneal adhesion biopsies","description":null,"abstract":"RNA-sequencing analysis was carried out on mesothelial cells isolated from peritoneal adhesion biopsies and compared to control human peritoneal mesothelial cells to identify a mesothelial-to-mesenchymal transition (MMT)-related gene signature in patients.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-02T10:43:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005750","title":"Single_cell_characterization_of_T_cell_lymphoma_","description":"Lymphomas are types of blood cancer derived from lymphocytes, and can be classified into two main categories, Hodgkin's lymphomas (HL) and non-Hodgkin lymphomas (NHL). T-cell lymphoma is a type of NHL that develops from T lymphocytes and accounts for 10-15% of total NHL cases. As a rare disease, T-cell lymphoma is functionally, pathologically, and clinically complex and heterogeneous. The 2016 revision of the WHO classification has listed 29 subtypes of mature T/NK-cell neoplasms, among which over 25 are T lymphocyte in origin. These subtypes of T-cell lymphomas have different biological behaviours and clinical prognosis.   Clinically, T-cell lymphoma ranges from indolent (slow-growing) to aggressive (fast-growing and spreading) disease. According to the guideline booklet provided by the Lymphoma Research Foundation (https://lymphoma.org/aboutlymphoma/nhl/), indolent T-cell lymphoma subtypes include adult T-cell leukaemia/lymphoma (ATLL), cutaneous T-cell lymphoma (CTCL), and mycosis fungoides (MF), while the aggressive subtypes include anaplastic large cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AITL), peripheral T-cell lymphoma (PTCL), and T lymphoblastic lymphoma (TLBL). PTCL and ALCL represent the most common subtypes of aggressive T-cell lymphoma whereas TLBL is a rare and aggressive subtype mostly diagnosed in children. In this study, we will use single cell RNA sequencing and single cell multiomic methods three aggressive T-cell lymphoma subtypes (ALCL, PTCL and TLBL) and try to gain a deeper insight into the genotypic and phenotypic features of these T-cell lymphomas.","abstract":"T-cell lymphoma is a type of non-Hodgkin lymphoma that develops from T lymphocytes. Many efforts have been made in previous studies to shed light on tumour behaviors and the molecular basis of different T-cell lymphoma subtypes. However, fundamental questions such as the underlying mechanism of T cell lymphomagenesis and cell of origin of different tumours remain largely unknown and warrant further characterization. On the other hand, previous studies have largely relied on methods that can only investigate a tumour from a bulk perspective, limiting their power in dissecting subpopulations to account for intra-tumour heterogeneity and multicellular subtypes within a single tumour. In this study, we will use single cell RNA sequencing and single cell multiomic methods three aggressive T-cell lymphoma subtypes (ALCL, PTCL and TLBL) and try to gain a deeper insight into the genotypic and phenotypic features of these T-cell lymphomas","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-02T15:05:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005751","title":"WGS and WES data of  invasive micropapillary carcinoma of breast","description":null,"abstract":"This study contains whole genome sequencing data, whole exon sequencing data and mutation files of IMPC tumor and normal tissue sample.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005752","title":"Multi-omic dataset of neuroendocrine neoplasm organoids","description":"This dataset corresponds to one of the first biobanks for the understudied neuroendocrine neoplasms from multiple grades and body sites (lung, pancreas, small intestine). It contains whole-genome sequencing data for original tumors, patient-derived tumor organoids at multiple passages, and matched normal tissue, and RNA-seq data for the original tumor and patient-derived tumor organoids.","abstract":"This dataset corresponds to one of the first biobanks for the understudied neuroendocrine neoplasms from multiple grades and body sites (lung, pancreas, small intestine). It contains whole-genome sequencing data for original tumors, patient-derived tumor organoids at multiple passages, and matched normal tissue, and RNA-seq data for the original tumor and patient-derived tumor organoids.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-03T14:28:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005753","title":"Genome-wide Rare Variant Score Associates With Morphological Subtypes of Autism Spectrum Disorder","description":"Defining different genetic subtypes of Autism Spectrum Disorder (ASD) can help predict developmental outcomes. Based on minor physical and major congenital anomalies, we categorized 325 Canadian children with ASD into dysmorphic and non-dysmorphic subgroupings. We developed a method to calculate a genome-wide rare variant score (GRVS) from whole-genome sequencing (WGS) data for each ASD proband. GRVS is a sum of the number of variants in morphology-associated coding and non-coding regions, weighted by their effect sizes. Probands with dysmorphic ASD had a significantly higher GRVS compared to those with non-dysmorphic ASD (P= 0.027). Using the polygenic transmission disequilibrium test, we observed an over-transmission of ASD-associated common variants in non-dysmorphic ASD probands (P= 2.9×10-3). We replicated our findings using 442 ASD probands that had accompanying morphology data in the Simons Simplex Collection. Our findings provide support for an alternative genomic classification of ASD subgroups using morphology data, which may inform intervention protocols.","abstract":"Defining different genetic subtypes of Autism Spectrum Disorder (ASD) can help predict developmental outcomes. Based on minor physical and major congenital anomalies, we categorized 325 Canadian children with ASD into dysmorphic and non-dysmorphic subgroupings. We developed a method to calculate a genome-wide rare variant score (GRVS) from whole-genome sequencing (WGS) data for each ASD proband. GRVS is a sum of the number of variants in morphology-associated coding and non-coding regions, weighted by their effect sizes. Probands with dysmorphic ASD had a significantly higher GRVS compared to those with non-dysmorphic ASD (P= 0.027). Using the polygenic transmission disequilibrium test, we observed an over-transmission of ASD-associated common variants in non-dysmorphic ASD probands (P= 2.9×10-3). We replicated our findings using 442 ASD probands that had accompanying morphology data in the Simons Simplex Collection. Our findings provide support for an alternative genomic classification of ASD subgroups using morphology data, which may inform intervention protocols.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-03T18:55:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005754","title":"Chromosomal microarray analysis of 410 Han Chinese patients with autism spectrum disorder or unexplained intellectual disability and developmental delay","description":null,"abstract":"Copy number variants (CNVs) are recognized as a crucial genetic cause of \nneurodevelopmental disorders (NDDs). To contribute more worldwide clinical genomics data, we investigated the genetic etiology of 410 Han Chinese patients with NDDs (151 with autism and 259 with unexplained intellectual disability (ID) and developmental delay (DD)) using chromosomal microarray analysis (CMA, Affymetrix).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005755","title":"Targeted sequencing data and shallow whole genome sequencing data of Follicular lymphoma.","description":"Contain data of 2 studies\n1: 82 nodal stage 1 FL cases and 139 stage III/IV cases \n2: 44 watch and wait stage III/IV and 46  Immediate treatment stage III/IV\n\ntargeted sequencing data of 369 genes and 12 translocation regions\nwhole genome shallow sequencing data","abstract":"Contain data of 2 studies\n1: 82 nodal stage 1 FL cases and 139 stage III/IV cases \n2: 44 watch and wait stage III/IV and 46  Immediate treatment stage III/IV\n\ntargeted sequencing data of 369 genes and 12 translocation regions\nwhole genome shallow sequencing data","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-04T08:42:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005756","title":"WGS_11pcw_fetus_hdbr_15951_DNA","description":"Mutations act as molecular barcodes detailing the origins of the cells that compose a tissue. To generate a high resolution map of the clonal origins and migration of cells during early human development, we will perform whole genome sequencing across the extensively sampled tissues of fetuses. Furthermore, the somatic mutations will reveal in utero mutational processes.","abstract":"Mutations act as molecular barcodes detailing the origins of the cells that compose a tissue. To generate a high resolution map of the clonal origins and migration of cells during early human development, we will perform whole genome sequencing across the extensively sampled tissues of fetuses. Furthermore, the somatic mutations will reveal in utero mutational processes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-04T12:43:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005757","title":"A critical spotlight on the paradigms of FFPE-DNA sequencing","description":null,"abstract":"Formalin-fixed, paraffin-embedded (FFPE) tissue is the most widely available material for diagnostics and retrospective clinical studies. Reliable sequencing data obtained from such specimens would have enormous potential for basic and clinical research. However, formaldehyde fixation introduces chemical modifications which ultimately can lead to false interpretations. Here we describe a start-to-end approach to mitigate FFPE-problems comprising preanalytical sample specification and quality, repair treatments, analytical sample preparation, and bioinformatic sub-processes. We have also developed an alternative sequential DNA repair technique (IQBErepair) addressing the cause of formalin-induced false positives: too low and uneven coverage. For low-input approaches this technique increased the unique on-target bases by 53% and 80% in two independent centers, respectively. Furthermore, we present other measures to reduce FFPE artifacts: replicate strategies (up to 98% for 1% VAF detection threshold), bioinformatic filtering (&amp;gt;99.9%). Combined with general recommendations for sample quality and preparation this can create reliable data quality, even from low amounts (50 ng) of low-quality (DIN 2.0/5% Q129 bp/Q41 bp) FFPE-DNA.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-05T09:59:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005758","title":"Detection of Cancer Mutations by Urine Liquid Biopsy in Bladder Cancer Patients","description":"The management of bladder cancer faces multiple challenges concerning the diagnostics and fol-low-up approaches. The standard diagnostic test is invasive cystoscopy. Urine cytology and re-cently proposed urine-based biomarkers still could not replace cystoscopy, thus prompting calls for improvements. Here, we explore urine liquid biopsy to detect cancer mutations for therapeutic and prognostic assessment and subsequently evaluate the utility of urine as a suitable specimen in diagnosing bladder cancer. Our findings show that the analysis of pre-and post-operative urine enables the characterization of specific tumor mutations, which can be used to diagnose and evaluate a patient’s prognosis and therapy response.","abstract":"The management of bladder cancer faces multiple challenges concerning the diagnostics and fol-low-up approaches. The standard diagnostic test is invasive cystoscopy. Urine cytology and re-cently proposed urine-based biomarkers still could not replace cystoscopy, thus prompting calls for improvements. Here, we explore urine liquid biopsy to detect cancer mutations for therapeutic and prognostic assessment and subsequently evaluate the utility of urine as a suitable specimen in diagnosing bladder cancer. Our findings show that the analysis of pre-and post-operative urine enables the characterization of specific tumor mutations, which can be used to diagnose and evaluate a patient’s prognosis and therapy response.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-05T10:07:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005759","title":"DERMATLAS__Poroma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are poromas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are poromas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-05T10:58:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005760","title":"Genomics of pediatric myeloid neoplasms","description":"Genomic profiling of pediatric myeloid tumors (AML, therapy-related myeloid neoplasms, MDS and others) has shown significant differences when compared adult myeloid neoplasms. This includes the recognition of pediatric-enriched entities including UBTF-TD and NUP98 rearranged leukemias. Collectively we have described over 23 unique molecular subtypes of pediatric AML with unique expression signatures, driver mutations, patterns of cooperating mutations and distinct outcomes. Some of the subtypes (KMT2A and NUP98, for example) have remarkable heterogeneity in fusions partners, cellular phenotypes and molecular signatures.","abstract":"Genomic profiling of pediatric myeloid tumors (AML, therapy-related myeloid neoplasms, MDS and others) has shown significant differences when compared adult myeloid neoplasms. This includes the recognition of pediatric-enriched entities including UBTF-TD and NUP98 rearranged leukemias. Collectively we have described over 23 unique molecular subtypes of pediatric AML with unique expression signatures, driver mutations, patterns of cooperating mutations and distinct outcomes. Some of the subtypes (KMT2A and NUP98, for example) have remarkable heterogeneity in fusions partners, cellular phenotypes and molecular signatures.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-05T20:12:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005761","title":"Exome sequencing","description":"Human telomere biology disorders (TBD), a heterogeneous group of disorders characterized by telomere attrition and premature aging phenotypes, are caused by inherited loss-of-function mutations in telomere-associated genes. Here, we identify three germline heterozygous missense variants in RPA1 gene in four unrelated probands presenting with short telomeres and varying clinical features of TBD including bone marrow failure, myelodysplastic syndrome, T- and B-cell lymphopenia, pulmonary fibrosis, and skin manifestations. All variants cluster to DNA binding domain A of RPA1 protein. RPA1 is an essential single-strand DNA-binding protein essential for DNA replication and repair. RPA1 has been implicated in telomere maintenance but the mechanism remains elusive. Thus far, no genetic disorder had been linked to RPA1. Using FRET assays, we showed that RPA1E240K and RPA1V227A exhibit increased binding to single-strand and telomeric DNA, implying a gain in DNA-binding function while RPA1T270A has binding properties similar to wild type. To study the mutational effect, RPA1E240K, with the highest binding capacity, was knocked-in iPSCs using CRISPR/Cas9, which showed severe telomere shortening and impaired hematopoietic differentiation. Furthermore, in the RPA1E240K patient, stable blood counts over two decades due coincided with clonal rescue hematopoiesis with an RNA-degrading truncating RPA1 mutation and a uniparental isodisomy 17p with loss of RPA1E240K allele. Using single cell DNA sequencing, the two somatic genetic rescue events were proven to be independently acquired in hematopoietic stem cells. In summary, we describe the first human disease caused by germline RPA1 variants in individuals with TBD.","abstract":"Human telomere biology disorders (TBD), a heterogeneous group of disorders characterized by telomere attrition and premature aging phenotypes, are caused by inherited loss-of-function mutations in telomere-associated genes. Here, we identify three germline heterozygous missense variants in RPA1 gene in four unrelated probands presenting with short telomeres and varying clinical features of TBD including bone marrow failure, myelodysplastic syndrome, T- and B-cell lymphopenia, pulmonary fibrosis, and skin manifestations. All variants cluster to DNA binding domain A of RPA1 protein. RPA1 is an essential single-strand DNA-binding protein essential for DNA replication and repair. RPA1 has been implicated in telomere maintenance but the mechanism remains elusive. Thus far, no genetic disorder had been linked to RPA1. Using FRET assays, we showed that RPA1E240K and RPA1V227A exhibit increased binding to single-strand and telomeric DNA, implying a gain in DNA-binding function while RPA1T270A has binding properties similar to wild type. To study the mutational effect, RPA1E240K, with the highest binding capacity, was knocked-in iPSCs using CRISPR/Cas9, which showed severe telomere shortening and impaired hematopoietic differentiation. Furthermore, in the RPA1E240K patient, stable blood counts over two decades due coincided with clonal rescue hematopoiesis with an RNA-degrading truncating RPA1 mutation and a uniparental isodisomy 17p with loss of RPA1E240K allele. Using single cell DNA sequencing, the two somatic genetic rescue events were proven to be independently acquired in hematopoietic stem cells. In summary, we describe the first human disease caused by germline RPA1 variants in individuals with TBD.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-07T17:31:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005762","title":"Single cell DNA sequencing and cell-surface protein analysis","description":"Human telomere biology disorders (TBD), a heterogeneous group of disorders characterized by telomere attrition and premature aging phenotypes, are caused by inherited loss-of-function mutations in telomere-associated genes. Here, we identify three germline heterozygous missense variants in RPA1 gene in four unrelated probands presenting with short telomeres and varying clinical features of TBD including bone marrow failure, myelodysplastic syndrome, T- and B-cell lymphopenia, pulmonary fibrosis, and skin manifestations. All variants cluster to DNA binding domain A of RPA1 protein. RPA1 is an essential single-strand DNA-binding protein essential for DNA replication and repair. RPA1 has been implicated in telomere maintenance but the mechanism remains elusive. Thus far, no genetic disorder had been linked to RPA1. Using FRET assays, we showed that RPA1E240K and RPA1V227A exhibit increased binding to single-strand and telomeric DNA, implying a gain in DNA-binding function while RPA1T270A has binding properties similar to wild type. To study the mutational effect, RPA1E240K, with the highest binding capacity, was knocked-in iPSCs using CRISPR/Cas9, which showed severe telomere shortening and impaired hematopoietic differentiation. Furthermore, in the RPA1E240K patient, stable blood counts over two decades due coincided with clonal rescue hematopoiesis with an RNA-degrading truncating RPA1 mutation and a uniparental isodisomy 17p with loss of RPA1E240K allele. Using single cell DNA sequencing, the two somatic genetic rescue events were proven to be independently acquired in hematopoietic stem cells. In summary, we describe the first human disease caused by germline RPA1 variants in individuals with TBD.","abstract":"Human telomere biology disorders (TBD), a heterogeneous group of disorders characterized by telomere attrition and premature aging phenotypes, are caused by inherited loss-of-function mutations in telomere-associated genes. Here, we identify three germline heterozygous missense variants in RPA1 gene in four unrelated probands presenting with short telomeres and varying clinical features of TBD including bone marrow failure, myelodysplastic syndrome, T- and B-cell lymphopenia, pulmonary fibrosis, and skin manifestations. All variants cluster to DNA binding domain A of RPA1 protein. RPA1 is an essential single-strand DNA-binding protein essential for DNA replication and repair. RPA1 has been implicated in telomere maintenance but the mechanism remains elusive. Thus far, no genetic disorder had been linked to RPA1. Using FRET assays, we showed that RPA1E240K and RPA1V227A exhibit increased binding to single-strand and telomeric DNA, implying a gain in DNA-binding function while RPA1T270A has binding properties similar to wild type. To study the mutational effect, RPA1E240K, with the highest binding capacity, was knocked-in iPSCs using CRISPR/Cas9, which showed severe telomere shortening and impaired hematopoietic differentiation. Furthermore, in the RPA1E240K patient, stable blood counts over two decades due coincided with clonal rescue hematopoiesis with an RNA-degrading truncating RPA1 mutation and a uniparental isodisomy 17p with loss of RPA1E240K allele. Using single cell DNA sequencing, the two somatic genetic rescue events were proven to be independently acquired in hematopoietic stem cells. In summary, we describe the first human disease caused by germline RPA1 variants in individuals with TBD.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005763","title":"CMA study for ASD, ID/DD","description":null,"abstract":"Copy number variants (CNVs) are recognized as a crucial genetic cause of \nneurodevelopmental disorders (NDDs). Chromosomal microarray analysis (CMA) has been utilized to detect CNVs in clinical practice, but most reports are still from populations of European ancestry. To contribute more worldwide clinical genomics data, we investigated the genetic etiology of 410 Han Chinese patients with NDDs using CMA (Affymetrix) after G-banding karyotyping.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005764","title":"JEM 20211004R","description":null,"abstract":"Our mission is to undertake ground breaking research, combining fundamental science and strong clinical interactions, to uncover the mechanism of disease of our patients, ultimately to provide a diagnosis and improved treatments. SLE is an autoimmune disease with a strong genetic component. Genome-wide association studies (GWAS) have revealed that multiple common variants confer genetic susceptibility to SLE, defining key pathways involved in disease pathogenesis.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-08T03:43:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005765","title":"Whole-exome sequencing of paired tumour/blood of 58 T1 stage bladder cancer patients","description":"To understand the molecular determinants that underpin the clinical heterogeneity of non-muscle-invasive bladder cancer (NMIBC) we carried out whole-exome sequencing (WES) of stage T1 bladder tumours to identify prognostic biomarkers and novel therapeutic targets. The study includes paired tumour/blood samples of 58 T1 stage bladder cancer patients.","abstract":"To understand the molecular determinants that underpin the clinical heterogeneity of non-muscle-invasive bladder cancer (NMIBC) we carried out whole-exome sequencing (WES) of stage T1 bladder tumours to identify prognostic biomarkers and novel therapeutic targets. The study includes paired tumour/blood samples of 58 T1 stage bladder cancer patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-08T12:05:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005766","title":"Targeted sequencing of paired tumour/blood of 78 Ta stage bladder cancer patients","description":"In continuation of our whole-exome and targeted sequencing study on non-muscle-invasive bladder cancer, we carried out this targeted paired tumour/blood sequencing study including 78 Ta stage bladder cancer patients.  Agilent’s SureDesign tool was used to design a 1.133 Mb SureSelect custom capture for all coding exons of the 140 selected candidate genes.","abstract":"In continuation of our whole-exome and targeted sequencing study on non-muscle-invasive bladder cancer, we carried out this targeted paired tumour/blood sequencing study including 78 Ta stage bladder cancer patients.  Agilent’s SureDesign tool was used to design a 1.133 Mb SureSelect custom capture for all coding exons of the 140 selected candidate genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-08T12:05:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005767","title":"Targeted sequencing of paired tumour/blood of 34 T1 stage bladder cancer patients","description":"Stage T1 bladder cancer presents a high risk of progression and requires improved understanding.  In continuation of our whole-exome sequencing study on this subtype of the disease, we carried out this targeted paired tumour/blood sequencing study including 34 T1 stage bladder cancer patients.  Agilent’s SureDesign tool was used to design a 1.133 Mb SureSelect custom capture for all coding exons of the 140 selected candidate genes.","abstract":"Stage T1 bladder cancer presents a high risk of progression and requires improved understanding.  In continuation of our whole-exome sequencing study on this subtype of the disease, we carried out this targeted paired tumour/blood sequencing study including 34 T1 stage bladder cancer patients.  Agilent’s SureDesign tool was used to design a 1.133 Mb SureSelect custom capture for all coding exons of the 140 selected candidate genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-08T12:05:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005768","title":"Somatic_mutations_in_normal_proximal_airway_epithelium_after_immunotherapy_RNA","description":"Immunotherapy has been shown to improve survival in advanced non-small cell lung cancers, especially those with high mutation burden. However, our understanding of how immunotherapy changes the clonal architecture in normal proximal airway epithelium is limited. In this study, single cells have been isolated from normal and pre-invasive lung cancer lesions before/after immunotherapy (PD-1 blocking antibody) from one patient. These have been grown into colonies that will then be studied by RNA-seq.","abstract":"Previously, we studied the landscape of somatic mutations in normal bronchial epithelium, which revealed that tobacco smoking increases the variance of mutation burden both within and between patients. Immunotherapy has been shown to improve survival in advanced non-small cell lung cancers, especially thoses with high mutation burden. However, our understanding of how immunotherapy changes the clonal architecture in normal proximal airway epithelium is limited. In this study, single cells have been isolated from normal and pre-invasive lung cancer lesions before/after immunotherapy (PD-1 blocking antibody) from one patient. These have been grown into colonies that will then be subjected to RNA-seq. Using RNA-seq, differences of gene expression between clones with high and low mutation burden, and the change of the number of expressed neoantigens after immunotherapy will be studied.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005769","title":"Genetic and immune landscape evolution defines subtypes of MMR deficient colorectal cancer","description":"Mismatch repair deficient colorectal cancers have high mutation loads and many respond to immune checkpoint-inhibitors. We investigated how genetic and immune landscapes co-evolve in these tumors. All cases had high truncal mutation loads. Driver aberrations showed a clear hierarchy despite pervasive intratumor heterogeneity: Those in WNT/βCatenin, mitogen-activated protein kinase and TGFβ receptor family genes were almost always truncal. Immune evasion drivers were predominantly subclonal and showed parallel evolution. Pan-tumor evolution, subclonal evolution, and evolutionary stasis of genetic immune evasion drivers defined three MMRd CRC subtypes with distinct T-cell infiltrates. These immune evasion drivers have been implicated in checkpoint-inhibitor resistance. Clonality and subtype assessments are hence critical for predictive immunotherapy biomarker development. Cancer cell PD-L1 expression was conditional on loss of the intestinal homeobox transcription factor CDX2. This explains infrequent PD-L1 expression by cancer cells and likely contributes to the high recurrence risk of MMRd CRCs with impaired CDX2 expression.","abstract":"Mismatch repair deficient colorectal cancers have high mutation loads and many respond to immune checkpoint-inhibitors. We investigated how genetic and immune landscapes co-evolve in these tumors. All cases had high truncal mutation loads. Driver aberrations showed a clear hierarchy despite pervasive intratumor heterogeneity: Those in WNT/βCatenin, mitogen-activated protein kinase and TGFβ receptor family genes were almost always truncal. Immune evasion drivers were predominantly subclonal and showed parallel evolution. Pan-tumor evolution, subclonal evolution, and evolutionary stasis of genetic immune evasion drivers defined three MMRd CRC subtypes with distinct T-cell infiltrates. These immune evasion drivers have been implicated in checkpoint-inhibitor resistance. Clonality and subtype assessments are hence critical for predictive immunotherapy biomarker development. Cancer cell PD-L1 expression was conditional on loss of the intestinal homeobox transcription factor CDX2. This explains infrequent PD-L1 expression by cancer cells and likely contributes to the high recurrence risk of MMRd CRCs with impaired CDX2 expression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-09T16:15:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005770","title":"Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce","description":null,"abstract":"Obesity is considered an important factor for many chronic diseases, including diabetes, cardiovascular disease and cancer. The expansion of adipose tissue in obesity is due to an increase in both adipocyte progenitor differentiation and mature adipocyte cell size. Adipocytes, however, are thought to be unable to divide or enter cell cycle. We demonstrate that mature human adipocytes unexpectedly display a gene and protein signature of cell cycle re-entry. Adipocyte cell cycle progression associates with obesity and hyperinsulinemia, with a concomitant increase in cell size, nuclear size and nuclear DNA content. However, chronic hyperinsulinemia in vitro or in patients, is associated with subsequent cell cycle exit, leading to a premature senescent transcriptomic and secretory profile in adipocytes. Premature senescence is rapidly becoming recognized as an important mediator of stress-induced tissue dysfunction. By demonstrating that adipocytes can re-enter cell cycle we define a mechanism for how mature, human adipocytes senesce and demonstrate that by targeting the adipocyte cell cycle program it is possible to impact adipocyte senescence and obesity-associated adipose tissue inflammation.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-10T11:58:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005771","title":"A meta-analysis of acne genome-wide association studies","description":"A meta-analysis of acne genome-wide association studies","abstract":"A meta-analysis of acne genome-wide association studies","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005772","title":"Acne GWAS meta-analysis","description":null,"abstract":"International meta-analysis of 14 acne studies from 9 independent cohorts.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-10T14:22:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005773","title":"Multi-omic analysis of cell-of-origin and epigenomic state in pediatric H3K27M gliomas","description":"It is not known whether midline pediatric gliomas driven by Histone 3 K27M mutations (oncohistones) or EZHIP expression (oncohistone-mimics) share a common cell-of-origin, or arise from distinct cell types with unique vulnerabilities to PRC2 inhibition and partner alterations. Here, we define the etiological and oncogenic relationship between pediatric midline gliomas characterized by inhibition of K27M and K27M-like oncohistones. We assemble an extensive reference for gliogenesis from the developing mouse and human fetal brain. With bulk and single-cell transcriptomics and epigenomics, we profiled a large cohort of primary tumors comprising H3.1K27M and H3.3K27M pontine gliomas, H3.3K27M thalamic gliomas, and EZHIP+ posterior fossa ependymomas. We focus on differences across axes of location (thalamus vs. pons vs. posterior fossa), tumor type (diffuse midline gliomas vs. ependymomas), and oncohistone (H3.1/2K27M vs. H3.3K27M vs. EZHIP). We use tumor molecular features to delineate transcriptional states and cell-of-origin in each entity. Finally, we use culture models in isogenic contexts to interrogate the effect of each oncohistone or mimic.","abstract":"It is not known whether midline pediatric gliomas driven by Histone 3 K27M mutations (oncohistones) or EZHIP expression (oncohistone-mimics) share a common cell-of-origin, or arise from distinct cell types with unique vulnerabilities to PRC2 inhibition and partner alterations. Here, we define the etiological and oncogenic relationship between pediatric midline gliomas characterized by inhibition of K27M and K27M-like oncohistones. We assemble an extensive reference for gliogenesis from the developing mouse and human fetal brain. With bulk and single-cell transcriptomics and epigenomics, we profiled a large cohort of primary tumors comprising H3.1K27M and H3.3K27M pontine gliomas, H3.3K27M thalamic gliomas, and EZHIP+ posterior fossa ependymomas. We focus on differences across axes of location (thalamus vs. pons vs. posterior fossa), tumor type (diffuse midline gliomas vs. ependymomas), and oncohistone (H3.1/2K27M vs. H3.3K27M vs. EZHIP). We use tumor molecular features to delineate transcriptional states and cell-of-origin in each entity. Finally, we use culture models in isogenic contexts to interrogate the effect of each oncohistone or mimic.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-10T15:17:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005774","title":"MC38_Tumour_model","description":"Sequencing study on MC38 tumour models","abstract":"Photoconvertable kaede mice were injected with MC38 tumour cells. In non-control mice, a laser was shown at the tumour. Mice were culled 5 hours post photoconversion.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005775","title":"VAXazpfizer","description":"Sequencing study of the effect of vaccination on different murine organs","abstract":"WT mice were given two 100ul doses of PBS, AZ or Pfizer vaccines. Meninges and spleen were taken to identify transcriptional changes by bulk RNAseq.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005776","title":"COVIDdura","description":"Sequencing study of the effect of infection with SARS-CoV2∂ on different murine organs","abstract":"hACE2-Tg mice were infected with SARS-Cov2 delta variant then culled. Meninges were collected to identify transcriptional changes by bulk RNA seq","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005777","title":"MI2BAC_transcriptome","description":"Sequencing study of the effect of Parkinson's Disease on mouse immune system","abstract":"MI2 BAC model of Parkinson's Disease is compared to controls","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005778","title":"HCA_Brain_Disease_Downs_Bayraktar_Spatial_","description":"Utilising Spatial Transcriptomics on Down syndrome (trisomy 21) and control fetal brain samples.","abstract":"Utilising Spatial Transcriptomics on Down syndrome (trisomy 21) and control fetal brain samples. In this study, we apply spatial transcriptomics to Down syndrome (trisomy 21) and control fetal brain samples from a range of cortical brain regions and time-points during mid-gestation (post-conception weeks 12 to 19). We aim to understand how and which cell types, cortical regions and neural circuits are affected in Down syndrome and how this could relate to the specific cognitive symptoms and high prevalence of dementia in patients. We furthermore envisage that studying fetal brain development in the presence of this selective gene dosage increase, will offer new insights into fundamental neurodevelopmental processes, including neural stem cell or progenitor proliferation/differentiation, interneuron differentiation/migration, oligodendrocyte development and cell-cell communication in the cortical ventricular zone. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005779","title":"Mutant p53 confers gain-of-function transcriptional activity in liver cancer","description":"Mutant p53 confers gain-of-function transcriptional activity in liver cancer","abstract":"Mutant p53 confers gain-of-function transcriptional activity in liver cancer","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-11T01:20:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005780","title":"Somatic_Mutagenesis_In_Cancer_Predisposition_Duplex","description":"This study investigates somatic mutation signatures in peripheral blood in a cohort of individuals with inherited cancer predisposition of unknown cause.","abstract":"Studies on individuals with particular inherited mutations in DNA repair genes have shown that mutational signatures of defective DNA repair are identifiable in peripheral blood samples. This project investigates individuals with inherited cancer predisposition to identify the unknown causes of intestinal polyposis and colorectal cancer predisposition.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005781","title":"Clinical impact of immune checkpoint inhibitor (ICI) response, DNA damage repair (DDR) gene mutations and immune-cell infiltration in subtypes of metastatic melanoma","description":"Our study identified that immune cell infiltration and DNA damage repair (DDR) gene mutations may have an impact in response to immune checkpoint inhibitors (ICI) treatment in metastatic melanoma but differs among melanoma subtypes. Therefore, a comprehensive understanding of the role of immune infiltration cells, DDR gene mutations and copy number alterations could act as prognostic biomarkers for the ICI treatment among metastatic melanoma subtype patients.","abstract":"Our study identified that immune cell infiltration and DNA damage repair (DDR) gene mutations may have an impact in response to immune checkpoint inhibitors (ICI) treatment in metastatic melanoma but differs among melanoma subtypes. Therefore, a comprehensive understanding of the role of immune infiltration cells, DDR gene mutations and copy number alterations could act as prognostic biomarkers for the ICI treatment among metastatic melanoma subtype patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-11T10:12:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005782","title":"Facioscapulohumeral dystrophy transcriptome signatures correlate with different stages of disease and are marked by different MRI biomarkers","description":"This project includes RNA-sequencing data from human FSHD and control skeletal muscle biopsies. This project includes data from 28 FSHD patients (total 37 samples, including vastus lateralis and tibialis anterior muscles) and 12 control individuals (total 24 samples, including vastus lateralis and tibialis anterior muscles).","abstract":"This project includes RNA-sequencing data from human FSHD and control skeletal muscle biopsies. This project includes data from 28 FSHD patients (total 37 samples, including vastus lateralis and tibialis anterior muscles) and 12 control individuals (total 24 samples, including vastus lateralis and tibialis anterior muscles).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-11T13:09:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005783","title":"Deep whole genome ctDNA chronology of treatment-resistant prostate cancer","description":null,"abstract":"Circulating tumor DNA (ctDNA) in blood plasma is an emerging tool for clinical cancer genotyping and longitudinal disease monitoring. We performed deep whole-genome sequencing of serial plasma and synchronous metastases in patients with aggressive prostate cancer. We comprehensively assess all classes of genomic alterations and demonstrate that ctDNA harbors multiple dominant populations whose evolutionary histories frequently indicate whole-genome doubling and shifts in mutational processes. Although tissue and ctDNA showed concordant clonally-expanded cancer driver alterations, each individual metastasis contributed only a minor share of total ctDNA. By comparing serial ctDNA before and after clinical progression on potent androgen receptor (AR) pathway inhibitors, we reveal population restructuring converging solely on AR augmentation as the dominant genomic driver of acquired treatment-resistance. Finally we leverage nucleosome footprints in ctDNA to infer mRNA abundance in synchronously biopsied metastases, including treatment-induced changes in AR pathway transcriptional activity.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-11T15:50:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005784","title":"Clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancers defined by genomic analysis","description":"Ductal Carcinoma In Situ (DCIS) is the most common form of pre-invasive \nbreast cancer and despite treatment a small fraction (5-10%) of DCIS\npatients present with invasive disease many years later.  A fundamental\nbiologic question is whether the invasive disease recurring in the same\nbreast is established by  tumor cells in the initial DCIS or\nrepresents  new unrelated disease.  To address this question, we\nperformed genomic analyses on the initial pure DCIS lesion and paired\ninvasive recurrent tumors in 95 patients together with single cell DNA\nsequencing in a subset of cases.  Our data shows that in 75% the\ninvasive recurrence was clonally related to the initial DCIS,\nsuggesting that the tumor cells were not eliminated during the initial\ntreatment with surgery +/- radiotherapy. Surprisingly however, 18% were\nclonally unrelated to the DCIS, representing new independent lineages,\nand 7% of cases were ambiguous.  Our findings show that although DCIS\nis often the precursor of  invasive recurrence, a significant fraction\nof invasive recurrences are unrelated to the initial DCIS. This\nknowledge is essential for accurate risk evaluation of DCIS treatment\nde-escalation strategies and the identification of predictive\nbiomarkers.","abstract":"Ductal Carcinoma In Situ (DCIS) is the most common form of pre-invasive \nbreast cancer and despite treatment a small fraction (5-10%) of DCIS\npatients present with invasive disease many years later.  A fundamental\nbiologic question is whether the invasive disease recurring in the same\nbreast is established by  tumor cells in the initial DCIS or\nrepresents  new unrelated disease.  To address this question, we\nperformed genomic analyses on the initial pure DCIS lesion and paired\ninvasive recurrent tumors in 95 patients together with single cell DNA\nsequencing in a subset of cases.  Our data shows that in 75% the\ninvasive recurrence was clonally related to the initial DCIS,\nsuggesting that the tumor cells were not eliminated during the initial\ntreatment with surgery +/- radiotherapy. Surprisingly however, 18% were\nclonally unrelated to the DCIS, representing new independent lineages,\nand 7% of cases were ambiguous.  Our findings show that although DCIS\nis often the precursor of  invasive recurrence, a significant fraction\nof invasive recurrences are unrelated to the initial DCIS. This\nknowledge is essential for accurate risk evaluation of DCIS treatment\nde-escalation strategies and the identification of predictive\nbiomarkers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-12T13:28:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005785","title":"DERMATLAS__Melanoma_MPNST_Cleveland_WES","description":"Desmoplastic melanomas (DM) can have very bland cytomorphologic features and shows significant histologic and immunophenotypic overlap with MPNST and neurofibroma, preventing classification in limited biopsies.    We have begun to utilize NGS as a diagnostic aid.  We previously characterized the molecular findings in conventional melanomas and borderline mimickers of melanoma (Zarabi SK, et al. 2020).  Our results showed that NGS diagnostically and biologically classified borderline melanocytic tumors as well as fluorescence in situ hybridization for melanoma. In this series, the test also gave prognostic information, with significance seen based on P53 mutational status.  Thus far, NGS has mostly clinically been used as a predictive tool for drug management, and predictive information is inherent in the test results. \n \nDespite their overlapping histologic and immunophenotypic features, DM, MPNST, and some NFs may have markedly different pathobiologic origins, treatments, and outcomes.  We hypothesize that the overall mutational tumor burden and the types of mutations seen will be significantly different in DM compared to MPNST and NF, allowing NGS to be utilized as a diagnostic (as well as predictive) aid.  This project will establish proof of concept for potential creation of targeted NGS panels that can be used as diagnostic tests, and establish appropriate guidelines for use in this setting.  In addition, the project will provide insight into the different biology between DM and MPNST.","abstract":"Desmoplastic melanomas (DM) can have very bland cytomorphologic features and shows significant histologic and immunophenotypic overlap with MPNST and neurofibroma, preventing classification in limited biopsies.    We have begun to utilize NGS as a diagnostic aid.  We previously characterized the molecular findings in conventional melanomas and borderline mimickers of melanoma (Zarabi SK, et al. 2020).  Our results showed that NGS diagnostically and biologically classified borderline melanocytic tumors as well as fluorescence in situ hybridization for melanoma. In this series, the test also gave prognostic information, with significance seen based on P53 mutational status.  Thus far, NGS has mostly clinically been used as a predictive tool for drug management, and predictive information is inherent in the test results. \n \nDespite their overlapping histologic and immunophenotypic features, DM, MPNST, and some NFs may have markedly different pathobiologic origins, treatments, and outcomes.  We hypothesize that the overall mutational tumor burden and the types of mutations seen will be significantly different in DM compared to MPNST and NF, allowing NGS to be utilized as a diagnostic (as well as predictive) aid.  This project will establish proof of concept for potential creation of targeted NGS panels that can be used as diagnostic tests, and establish appropriate guidelines for use in this setting.  In addition, the project will provide insight into the different biology between DM and MPNST.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005786","title":"Extensive three-dimensional intratumor proteomic heterogeneity revealed by multiregion sampling in high-grade serous ovarian tumor specimens","description":"Enriched tumor epithelium, tumor-associated stroma, and whole tissue were collected by laser microdissection from thin sections across spatially separated levels of ten high-grade serous ovarian carcinomas (HGSOCs) and analyzed by mass spectrometry, reverse phase protein arrays, and RNA sequencing. Unsupervised analyses of protein abundance data revealed independent clustering of an enriched stroma and enriched tumor epithelium, with whole tumor tissue clustering driven by overall tumor “purity.” Comparing these data to previously defined prognostic HGSOC molecular subtypes revealed protein and transcript expression from tumor epithelium correlated with the differentiated subtype, whereas stromal proteins (and transcripts) correlated with the mesenchymal subtype. Protein and transcript abundance in the tumor epithelium and stroma exhibited decreased correlation in samples collected just hundreds of microns apart. These data reveal substantial tumor microenvironment protein heterogeneity that directly bears on prognostic signatures, biomarker discovery, and cancer pathophysiology and underscore the need to enrich cellular subpopulations for expression profiling. (Companion proteomic data is available in the ProteomeXchange Consortium, PRIDE: PXD026570).","abstract":"Enriched tumor epithelium, tumor-associated stroma, and whole tissue were collected by laser microdissection from thin sections across spatially separated levels of ten high-grade serous ovarian carcinomas (HGSOCs) and analyzed by mass spectrometry, reverse phase protein arrays, and RNA sequencing. Unsupervised analyses of protein abundance data revealed independent clustering of an enriched stroma and enriched tumor epithelium, with whole tumor tissue clustering driven by overall tumor “purity.” Comparing these data to previously defined prognostic HGSOC molecular subtypes revealed protein and transcript expression from tumor epithelium correlated with the differentiated subtype, whereas stromal proteins (and transcripts) correlated with the mesenchymal subtype. Protein and transcript abundance in the tumor epithelium and stroma exhibited decreased correlation in samples collected just hundreds of microns apart. These data reveal substantial tumor microenvironment protein heterogeneity that directly bears on prognostic signatures, biomarker discovery, and cancer pathophysiology and underscore the need to enrich cellular subpopulations for expression profiling. (Companion proteomic data is available in the ProteomeXchange Consortium, PRIDE: PXD026570).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-12T20:21:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005787","title":"Resolving the immune landscape of human prostate at a single cell level  in health and cancer","description":"The prostate gland produces prostatic fluid, high in zinc and citrate and essential for the maintenance of spermatozoa. Prostate cancer is a common condition with limited treatment efficacy in castration-resistant metastatic disease, including with immune checkpoint inhibitors. We used single-cell RNA-sequencing to perform an unbiased assessment of the cellular landscape of human prostate and identified a previously unappreciated subset of tumour-enriched androgen receptor-negative luminal epithelial cells, with increased expression of cancer-associated genes. We also found a variety of innate and adaptive immune cells in normal prostate that were transcriptionally perturbed in prostate cancer. An exception was a unique, prostate-specific, zinc transporter-expressing macrophage population (MAC-MT), that contributed to tissue zinc accumulation in homeostasis, but showed enhanced inflammatory gene expression in tumours, including T cell-recruiting chemokines. Remarkably, enrichment of the MAC-MT signature in cancer biopsies was associated with improved disease-free survival, suggesting beneficial anti-tumour functions.","abstract":"The prostate gland produces prostatic fluid, high in zinc and citrate and essential for the maintenance of spermatozoa. Prostate cancer is a common condition with limited treatment efficacy in castration-resistant metastatic disease, including with immune checkpoint inhibitors. We used single-cell RNA-sequencing to perform an unbiased assessment of the cellular landscape of human prostate and identified a previously unappreciated subset of tumour-enriched androgen receptor-negative luminal epithelial cells, with increased expression of cancer-associated genes. We also found a variety of innate and adaptive immune cells in normal prostate that were transcriptionally perturbed in prostate cancer. An exception was a unique, prostate-specific, zinc transporter-expressing macrophage population (MAC-MT), that contributed to tissue zinc accumulation in homeostasis, but showed enhanced inflammatory gene expression in tumours, including T cell-recruiting chemokines. Remarkably, enrichment of the MAC-MT signature in cancer biopsies was associated with improved disease-free survival, suggesting beneficial anti-tumour functions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-14T09:02:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005788","title":"Myeloma methylation","description":null,"abstract":"Methylation data on 442 multiple myeloma patients. Multiple myeloma cells from patient bone marrow aspirates were obtained at diagnosis and purified (&gt;95%) using immune-magnetic CD138-cell sorting. RNA and DNA were extracted using RNA/DNA mini kit or Allprep kits (QIAGEN) according to manufacturers’ instructions.  The EZ DNA Methylation kit (Zymo Research) was used for bisulfite conversion of genomic DNA. Tumor DNA methylation was profiled using Illumina Infinium HumanMethylation450 (450k).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-14T10:16:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005789","title":"DERMATLAS__Melanoma_MPNST_Cleveland_RNAseq","description":"Desmoplastic melanomas (DM) can have very bland cytomorphologic features and shows significant histologic and immunophenotypic overlap with MPNST and neurofibroma, preventing classification in limited biopsies.    We have begun to utilize NGS as a diagnostic aid.  We previously characterized the molecular findings in conventional melanomas and borderline mimickers of melanoma (Zarabi SK, et al. 2020).  Our results showed that NGS diagnostically and biologically classified borderline melanocytic tumors as well as fluorescence in situ hybridization for melanoma. In this series, the test also gave prognostic information, with significance seen based on P53 mutational status.  Thus far, NGS has mostly clinically been used as a predictive tool for drug management, and predictive information is inherent in the test results. \n \nDespite their overlapping histologic and immunophenotypic features, DM, MPNST, and some NFs may have markedly different pathobiologic origins, treatments, and outcomes.  We hypothesize that the overall mutational tumor burden and the types of mutations seen will be significantly different in DM compared to MPNST and NF, allowing NGS to be utilized as a diagnostic (as well as predictive) aid.  This project will establish proof of concept for potential creation of targeted NGS panels that can be used as diagnostic tests, and establish appropriate guidelines for use in this setting.  In addition, the project will provide insight into the different biology between DM and MPNST.","abstract":"Desmoplastic melanomas (DM) can have very bland cytomorphologic features and shows significant histologic and immunophenotypic overlap with MPNST and neurofibroma, preventing classification in limited biopsies.    We have begun to utilize NGS as a diagnostic aid.  We previously characterized the molecular findings in conventional melanomas and borderline mimickers of melanoma (Zarabi SK, et al. 2020).  Our results showed that NGS diagnostically and biologically classified borderline melanocytic tumors as well as fluorescence in situ hybridization for melanoma. In this series, the test also gave prognostic information, with significance seen based on P53 mutational status.  Thus far, NGS has mostly clinically been used as a predictive tool for drug management, and predictive information is inherent in the test results. \n \nDespite their overlapping histologic and immunophenotypic features, DM, MPNST, and some NFs may have markedly different pathobiologic origins, treatments, and outcomes.  We hypothesize that the overall mutational tumor burden and the types of mutations seen will be significantly different in DM compared to MPNST and NF, allowing NGS to be utilized as a diagnostic (as well as predictive) aid.  This project will establish proof of concept for potential creation of targeted NGS panels that can be used as diagnostic tests, and establish appropriate guidelines for use in this setting.  In addition, the project will provide insight into the different biology between DM and MPNST.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005790","title":"The_role_of_clonal_haematopoiesis_in_immune_mediated_inflammatory_disease","description":"The overall objective is to test the hypothesis that clonal haematopoiesis (CH) is associated with immune-mediated inflammatory disease","abstract":"The overall objective is to test the hypothesis that clonal haematopoiesis (CH) is associated with immune-mediated inflammatory disease","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005791","title":"Mutations in ALK signaling pathways conferring resistance to ALK inhibitor treatment lead to collateral vulnerabilities in neuroblastoma cells","description":null,"abstract":"Development of resistance to targeted therapies has tempered initial optimism that precision oncology would improve poor outcomes for cancer patients. Resistance mechanisms, however, can also confer new resistance-specific vulnerabilities, termed collateral sensitivities. Here we investigated ALK inhibitor (ALKi) resistance in neuroblastoma, a childhood cancer frequently affected by activating ALK alterations. Both genome-wide CRISPR-Cas9-based screens and preclinical spontaneous ALKi resistance models identified NF1 loss and activating NRAS Q61K mutations to confer resistance to chemically diverse ALKi. Moreover, human neuroblastomas recurrently developed de novo loss of NF1 and activating RAS mutations after ALKi treatment, leading to therapy resistance. Pathway-specific perturbations confirmed that NF1 loss and activating RAS mutations lead to RAS-MAPK signaling even in the presence of ALKi. Intriguingly, NF1 loss rendered neuroblastoma cells hypersensitive to MEK inhibition. Thus, we provide a clinically relevant mechanistic model of ALKi resistance\nin neuroblastoma and highlight new clinically actionable collateral sensitivities in resistant cells.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-15T14:14:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005792","title":"The pseudoautosomal gene SLC25A6 is involved in determining the QTc interval","description":null,"abstract":"Evidence points at a role of X chromosomal genes exhibiting a sex-biased expression pattern that contributes to the generally observed sexual dimorphism in health and disease. Here, we use in vivo zebrafish models and patients with sex chromosome aneuploidies to demonstrate that the inner mitochondrial membrane ADP/ATP translocase 3, encoded by the pseudoautosomal X chromosomal gene SLC25A6, is implicated in systolic duration and QT interval duration.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005793","title":"NOTCH-mutations drive immune-escape mechanisms in B cell malignancies","description":"Here we provide access to MCL expression data that were used for interrogating the molecular functions of NOTCH1 and NOTCH2, which are two of the most commonly mutated genes in CLL and MCL and associated with a poor clinical outcome. The mechanisms underlying how NOTCH1 contributes to disease progression, resistance to treatment and Richter’s transformation remain largely unknown. The main goal of this study is to compare the gene expression profile of primary MCL cells transduced with the intracellular part of NOTCH1 or NOTCH2 lacking of the PEST domain vs cells transduced with an empty vector.","abstract":"Here we provide access to MCL expression data that were used for interrogating the molecular functions of NOTCH1 and NOTCH2, which are two of the most commonly mutated genes in CLL and MCL and associated with a poor clinical outcome. The mechanisms underlying how NOTCH1 contributes to disease progression, resistance to treatment and Richter’s transformation remain largely unknown. The main goal of this study is to compare the gene expression profile of primary MCL cells transduced with the intracellular part of NOTCH1 or NOTCH2 lacking of the PEST domain vs cells transduced with an empty vector.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-16T12:42:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005794","title":"Profibrotic priming of airway cell types in idiopathic pulmonary fibrosis and drug inhibition in single-cell resolution","description":"The cause and etiology of idiopathic pulmonary fibrosis, a severe chronic lung disorder with limited treatment options, is still poorly understood. Early genetic studies hinted that airway epithelial cells play an important role in the development of IPF while more recent single-cell RNA sequencing atlases from explant IPF lungs have focused on macrophages. In this study, we used air-liquid interface cultures of primary cells taken from the subsegmental bronchi of IPF patients, reflecting early-stage fibrosis, to interrogate the single-cell transcriptional landscape of the airway mucosa. We identified IPF-enriched cell-cell interaction pathways. Moreover, we also observed that IPF cell types shared “core” signatures, where epithelial cells had a pro-inflammatory signature while fibroblasts had an early activation signature. Harnessing the in vitro culture system, we also treated the cells with nintedanib, pirfenidone, and saracatinib, an Src kinase inhibitor that could inhibit IPF progression, to investigate their effects on the previously described IPF signatures. Unfortunately, only certain signatures were positively affected by the three drugs. This study provides more insight into the disease mechanisms of IPF and is a key resource for the IPF community to further investigate the effects of pharmacological inhibition.","abstract":"The cause and etiology of idiopathic pulmonary fibrosis, a severe chronic lung disorder with limited treatment options, is still poorly understood. Early genetic studies hinted that airway epithelial cells play an important role in the development of IPF while more recent single-cell RNA sequencing atlases from explant IPF lungs have focused on macrophages. In this study, we used air-liquid interface cultures of primary cells taken from the subsegmental bronchi of IPF patients, reflecting early-stage fibrosis, to interrogate the single-cell transcriptional landscape of the airway mucosa. We identified IPF-enriched cell-cell interaction pathways. Moreover, we also observed that IPF cell types shared “core” signatures, where epithelial cells had a pro-inflammatory signature while fibroblasts had an early activation signature. Harnessing the in vitro culture system, we also treated the cells with nintedanib, pirfenidone, and saracatinib, an Src kinase inhibitor that could inhibit IPF progression, to investigate their effects on the previously described IPF signatures. Unfortunately, only certain signatures were positively affected by the three drugs. This study provides more insight into the disease mechanisms of IPF and is a key resource for the IPF community to further investigate the effects of pharmacological inhibition.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005795","title":"Sanger3_combinatorial_CRISPR_screen","description":"We plan to test gene pairs derived from two bioinformatic analyses (1. mutual exclusivity analysis and 2. paralog pairs analysis) for underlying synthetic lethal interactions using a bespoke CRISPR dual guide library to facilitate pairwise gene perturbation screening across 15 cancer cell lines from 5 cancer types. By comparing the fitness effects of simultaneous versus individual perturbation, we can identify pairs which significantly interact.","abstract":"Synthetic lethality remains an attractive therapeutic approach for exploiting gene loss in cancer, facilitating the targeting of loss-of-function events, classically considered unactionable by targeted therapies. Pairs of genes whose loss-of-function alterations appear mutually exclusive across cancer genomes may exhibit synthetic lethality, as concurrent loss is lethal and therefore rarely observed. Pairs of gene paralogs are also more likely to display synthetic lethality as given their functional similarity, one gene may compensate for the other’s individual loss, whilst simultaneous loss cannot be tolerated. By performing pairwise mutual exclusivity analysis of genomic alterations across the TCGA Pan-cancer (PANCAN) dataset, we identify mutually exclusive pairs of loss-of-function alterations, which represent candidate synthetic lethal interactions. Based on a machine-learning approach to predict synthetic lethality amongst paralog pairs, we determine a set of candidate synthetic lethal gene paralog pairs. We then identify which of these pairs involve a gene commonly lost in human cancers and therefore have clinical utility. We plan to test gene pairs derived from the mutual exclusivity and paralog analysis for underlying genetic interactions using a CRISPR/Cas9-based dual gene perturbation screen across 15 cancer cell lines from 5 cancer types. By comparing the fitness effects of simultaneous versus individual perturbation, we can identify pairs which significantly interact. Gene pairs which demonstrate interaction across multiple cell lines and cancer types will subsequently be functionally validated and further characterised to elucidate the biological mechanisms underpinning their interactions.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005796","title":"Analysis_of_T_Cell_Activation_and_treg_Suppression","description":"Isolated regulatory T -cells from healthy donors are expanded and subjected to gene-editing using CRISPR/Cas9 to delete genes possibly linked to the Treg suppressive capability. Changes in expression of the expanding Tregs are measured at 3 timepoints by RNA sequencing. These edited Tregs (eTregs) are then placed in a co-culture of naïve T cells and macrophages. We performed scRNA sequencing to assess regulation of T cell activation and perform sceQTL analysis.","abstract":"T cell activation is tightly regulated by delivery of stimulatory signals through antigen presenting cells and suppressive capacity exerted by regulatory T cells. Here, we have isolated Tregs from blood of healthy donors which were then activated using anti-CD3 anti-CD28. RNA-sequencing was performed to identify changes in gene-expression at three timepoints in order to identify changes in gene-expression caused by the expansion process. The expanded Tregs are then subjected to CRISPR/Cas9-editing and then co-cultured along with isolated naïve T-cells and polarised macrophages from the same healthy donor in the presence of anti-CD3 to identify genes linked to Treg suppressive capability. Single-cell gene expression was then performed on co-cultures containing CRISPR-Cas9-edited Tregs from 3 healthy donors in order to identify the genetic background of T-cell activation and Treg suppression.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005797","title":"Mexican Biobank Project","description":"In this study, we present the data from the Mexican Biobank Project: 50 WGS from individuals with Native American ancestry, and 6000 genotypes from samples from this project. This project highlights the necessity of better diversity representation in genomic databases is a scientific imperative.","abstract":"In this study, we present the data from the Mexican Biobank Project: 50 WGS from individuals with Native American ancestry, and 6000 genotypes from samples from this project. This project highlights the necessity of better diversity representation in genomic databases is a scientific imperative.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-18T14:00:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005798","title":"Persistence of circulating tumor DNA in breast cancer patients during neoadjuvant treatment is a significant predictor of poor tumor response","description":"Purpose:Accurate assessment of response during neoadjuvant systemic treatment (NST) poses a major clinical challenge. Therefore, a minimally-invasive assessment of tumor response based on cell-free circulating tumor DNA (ctDNA) may be beneficial to guide treatment decisions.Experimental Design: We profiled 93 genes in tissue from 193 early breast cancer patients. Patient-specific assays were designed to track ctDNA during NST from 145 patients with available plasma. ctDNA presence and levels were correlated with complete pathological response (pCR) and residual cancer burden (RCB) as well as with clinicopathologic characteristics of the tumor to identify potential proxies for ctDNA release. Moreover, we tested the predictive value of driver events identified in the tumor.Results:At baseline, ctDNA could be detected in 63/145 (43.4%) patients and persisted in 25/63 (39.7%) patients at mid-therapy (MT) and 15/63 (23.8%) patients at the end of treatment. ctDNA detection at MT was significantly associated with higher RCB (OR 0.062, 95% CI 0.01-0.48, P=0.0077). Out of 31 patients with detectable ctDNA at MT, 30 patients (96.8%) were non-responders (RCB II, n=8; RCB III, n=22) and only one patient responded to the treatment (RCB I). Considering all 145 patients with baseline (BL) plasma, none of the patients with RCB 0 and only 6.7% of patients with RCB I had ctDNA detectable at MT, while 30.6% and 29.6% of patients with RCB II/III, respectively, had a positive ctDNA result. Conclusion:Overall, our results demonstrate that the detection and persistence of ctDNA at mid-therapy may have the potential to negatively predict response to neoadjuvant treatment and identify patients who will not achieve pCR or be classified with RCB II/III.","abstract":"Purpose:Accurate assessment of response during neoadjuvant systemic treatment (NST) poses a major clinical challenge. Therefore, a minimally-invasive assessment of tumor response based on cell-free circulating tumor DNA (ctDNA) may be beneficial to guide treatment decisions.Experimental Design: We profiled 93 genes in tissue from 193 early breast cancer patients. Patient-specific assays were designed to track ctDNA during NST from 145 patients with available plasma. ctDNA presence and levels were correlated with complete pathological response (pCR) and residual cancer burden (RCB) as well as with clinicopathologic characteristics of the tumor to identify potential proxies for ctDNA release. Moreover, we tested the predictive value of driver events identified in the tumor.Results:At baseline, ctDNA could be detected in 63/145 (43.4%) patients and persisted in 25/63 (39.7%) patients at mid-therapy (MT) and 15/63 (23.8%) patients at the end of treatment. ctDNA detection at MT was significantly associated with higher RCB (OR 0.062, 95% CI 0.01-0.48, P=0.0077). Out of 31 patients with detectable ctDNA at MT, 30 patients (96.8%) were non-responders (RCB II, n=8; RCB III, n=22) and only one patient responded to the treatment (RCB I). Considering all 145 patients with baseline (BL) plasma, none of the patients with RCB 0 and only 6.7% of patients with RCB I had ctDNA detectable at MT, while 30.6% and 29.6% of patients with RCB II/III, respectively, had a positive ctDNA result. Conclusion:Overall, our results demonstrate that the detection and persistence of ctDNA at mid-therapy may have the potential to negatively predict response to neoadjuvant treatment and identify patients who will not achieve pCR or be classified with RCB II/III.","study_type":"Other","pubmed_ids":[34862246],"external_links":null,"is_released":true,"released_date":"2021-11-18T14:18:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005799","title":"Brain_Disease_Wellcome_Leap_Delta_Tissue_DNA","description":"Investigating how the tumour microenvironment regulates glioblastoma cell states using genomic analysis.","abstract":"\"Investigating how the tumour microenvironment regulates glioblastoma cell states using genomic analysis. The malignant brain tumour glioblastoma multiforme (GBM) displays significant levels of cellular, genetic, transcriptional and epigenetic\nheterogeneity. Recent studies have shown that individual GBM tumours are mixtures of recurrent cell states. These malignant cell\nstates express distinct transcriptional programs and stratify GBM subtypes with different tumour phenotypes. For instance, “proneural”\nGBMs mainly consist of cells that resemble neural progenitors that express the bHLH protein OLIG2. In contrast, “mesenchymal” GBMs\nare heavily invested with innate immune cells that may programme for immune evasion and are associated with the poorest survival\nrates amongst GBM subtypes. So called “glioma stem cells (GSC)” are thought to be tumour propagating and relatively resistant to\nchemo and radiotherapy5. However, GBM cell states are highly dynamic and exhibit plasticity as tumour cells can transition from one\nstate to another, shifting throughout tumour development as well as disease relapse after therapy. For example, we found that both\nexperimental glioma and human GBM shifted to an alternative (Wnt7) angiogenic programme after prolonged anti-VEGF treatment. It is\noften assumed that the tumour microenvironment (TME) regulates GBM cell states. However, we know little about how TME-derived\nsignals and intercellular interactions drive malignant cell state transitions in GBM. A comprehensive cellular and molecular\ncharacterisation of TME across GBMs and different tumour areas is lacking. Further, it is unclear whether different GBM cell states\nassociate with distinct or similar TME cells. We propose to focus on innate immune cells of the TME as potential determinants of GBM\ntherapeutic resistance. Macrophages and microglia are some of the most abundant cells in GBM tumours. In mesenchymal GBMs,\nmacrophage derived signals induce transcriptional programs in tumour cells that, in turn, lead to an immunosuppressive and protumourigenic\nTME. In preliminary studies we find that microglia confers resistance to the putative oncolytic Zika virus infection. Here,\nwe will comprehensively identify TME-derived signals that regulate GBM cell state and transitions using an innovative approach\ncombining multi-modal omics and spatial tissue profiling.\"","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-18T15:37:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005800","title":"Brain_Disease_Wellcome_Leap_Delta_Tissue_RNA","description":"Utilising Single-Nucleus sequencing to investigate how the tumour microenvironment regulates glioblastoma cell states.","abstract":"\"Utilising Single-Nucleus sequencing to investigate how the tumour microenvironment regulates glioblastoma cell states. The malignant brain tumour glioblastoma multiforme (GBM) displays significant levels of cellular, genetic, transcriptional and epigenetic\nheterogeneity. Recent studies have shown that individual GBM tumours are mixtures of recurrent cell states. These malignant cell\nstates express distinct transcriptional programs and stratify GBM subtypes with different tumour phenotypes. For instance, “proneural”\nGBMs mainly consist of cells that resemble neural progenitors that express the bHLH protein OLIG2. In contrast, “mesenchymal” GBMs\nare heavily invested with innate immune cells that may programme for immune evasion and are associated with the poorest survival\nrates amongst GBM subtypes. So called “glioma stem cells (GSC)” are thought to be tumour propagating and relatively resistant to\nchemo and radiotherapy5. However, GBM cell states are highly dynamic and exhibit plasticity as tumour cells can transition from one\nstate to another, shifting throughout tumour development as well as disease relapse after therapy. For example, we found that both\nexperimental glioma and human GBM shifted to an alternative (Wnt7) angiogenic programme after prolonged anti-VEGF treatment. It is\noften assumed that the tumour microenvironment (TME) regulates GBM cell states. However, we know little about how TME-derived\nsignals and intercellular interactions drive malignant cell state transitions in GBM. A comprehensive cellular and molecular\ncharacterisation of TME across GBMs and different tumour areas is lacking. Further, it is unclear whether different GBM cell states\nassociate with distinct or similar TME cells. We propose to focus on innate immune cells of the TME as potential determinants of GBM\ntherapeutic resistance. Macrophages and microglia are some of the most abundant cells in GBM tumours. In mesenchymal GBMs,\nmacrophage derived signals induce transcriptional programs in tumour cells that, in turn, lead to an immunosuppressive and protumourigenic\nTME. In preliminary studies we find that microglia confers resistance to the putative oncolytic Zika virus infection. Here,\nwe will comprehensively identify TME-derived signals that regulate GBM cell state and transitions using an innovative approach\ncombining multi-modal omics and spatial tissue profiling.\"","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-18T15:41:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005801","title":"Brain_Disease_Wellcome_Leap_Delta_Tissue_Spatial","description":"Utilising Spatial Transcriptomics to investigate how the tumour microenvironment regulates glioblastoma cell states.","abstract":"\"Utilising Spatial Transcriptomics to investigate how the tumour microenvironment regulates glioblastoma cell states. The malignant brain tumour glioblastoma multiforme (GBM) displays significant levels of cellular, genetic, transcriptional and epigenetic\nheterogeneity. Recent studies have shown that individual GBM tumours are mixtures of recurrent cell states. These malignant cell\nstates express distinct transcriptional programs and stratify GBM subtypes with different tumour phenotypes. For instance, “proneural”\nGBMs mainly consist of cells that resemble neural progenitors that express the bHLH protein OLIG2. In contrast, “mesenchymal” GBMs\nare heavily invested with innate immune cells that may programme for immune evasion and are associated with the poorest survival\nrates amongst GBM subtypes. So called “glioma stem cells (GSC)” are thought to be tumour propagating and relatively resistant to\nchemo and radiotherapy5. However, GBM cell states are highly dynamic and exhibit plasticity as tumour cells can transition from one\nstate to another, shifting throughout tumour development as well as disease relapse after therapy. For example, we found that both\nexperimental glioma and human GBM shifted to an alternative (Wnt7) angiogenic programme after prolonged anti-VEGF treatment. It is\noften assumed that the tumour microenvironment (TME) regulates GBM cell states. However, we know little about how TME-derived\nsignals and intercellular interactions drive malignant cell state transitions in GBM. A comprehensive cellular and molecular\ncharacterisation of TME across GBMs and different tumour areas is lacking. Further, it is unclear whether different GBM cell states\nassociate with distinct or similar TME cells. We propose to focus on innate immune cells of the TME as potential determinants of GBM\ntherapeutic resistance. Macrophages and microglia are some of the most abundant cells in GBM tumours. In mesenchymal GBMs,\nmacrophage derived signals induce transcriptional programs in tumour cells that, in turn, lead to an immunosuppressive and protumourigenic\nTME. In preliminary studies we find that microglia confers resistance to the putative oncolytic Zika virus infection. Here,\nwe will comprehensively identify TME-derived signals that regulate GBM cell state and transitions using an innovative approach\ncombining multi-modal omics and spatial tissue profiling.\"","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-18T15:44:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005802","title":"Anemia in DAP3 deficiency due to dyserythropoiesis","description":"Death-associated protein 3 (DAP3) is a subunit of the mitochondrial ribosome and plays a role in translation, apoptosis, fission and fusion of mitochondria, and A-to-I RNA editing. We identified a homozygous rare variant in DAP3 encoding R232Q by whole-exome sequencing of a child born with anemia who died after bone marrow graft failure. RNA sequencing of HSC-derived erythroblasts showed a reduction in A-to-I RNA editing in known erythroblast-specific genes in the patient compared to controls. Our data reveal an important role for DAP3 during erythropoiesis via regulation of mitochondrial health and provide evidence that A-to-I RNA editing is involved in this process.","abstract":"Death-associated protein 3 (DAP3) is a subunit of the mitochondrial ribosome and plays a role in translation, apoptosis, fission and fusion of mitochondria, and A-to-I RNA editing. We identified a homozygous rare variant in DAP3 encoding R232Q by whole-exome sequencing of a child born with anemia who died after bone marrow graft failure. RNA sequencing of HSC-derived erythroblasts showed a reduction in A-to-I RNA editing in known erythroblast-specific genes in the patient compared to controls. Our data reveal an important role for DAP3 during erythropoiesis via regulation of mitochondrial health and provide evidence that A-to-I RNA editing is involved in this process.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005803","title":"Mutational_and_clonal_landscape_of_atherosclerosis_WES","description":"Clonal expansions and invasion of Vascular Smooth Cells (VSMCs) from the vessel wall media into the intima have been reported by multiple publications that make use of genetic lineage tracing in mouse models of atherosclerosis. Importantly, these clonal expansions have been proposed to be driven by somatic mutations. Understanding whether the findings in mice can be extended to human atherosclerosis has major implications. Most notably, in mice, these expanding VSMCs have been proposed to contribute to the majority of cells in the plaque, including foamy macrophages . Our lab is ideally positioned to investigate this question, due to tools like Nanorate sequencing20 and LCM and low-input DNA sequencing. Firstly, I am going to use LCM sequencing to study whether there is any clonality in the atherosclerotic tissue and approximately when this process started in the individual’s life.  Secondly, I am going to use the recently developed Nanorate sequencing to screen for potential driver mutations in the atherosclerotic tissue.","abstract":"The data in this study will be generated by whole-genome sequencing of laser-dissected microbiopsies from atherosclerosis samples.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005804","title":"HCA_Adult_tissue_comparative_study_WSSS_RNA","description":"Comparative HCA study across multiple adult tissues","abstract":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions. Data dissemination: We will submit any data generated from this project to the Human Cell Atlas data coordination platform (DCP). The DCP is hosted at EMBL-EBI, providing multiple cloud platforms to host the data and data portals that will ensure rapid open access to the scientific community and opportunities to develop novel analysis tools.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005805","title":"HCA_Adult_tissue_comparative_study_WSSS_Spatial","description":"Comparative HCA study across multiple adult tissues","abstract":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions. Data dissemination: We will submit any data generated from this project to the Human Cell Atlas data coordination platform (DCP). The DCP is hosted at EMBL-EBI, providing multiple cloud platforms to host the data and data portals that will ensure rapid open access to the scientific community and opportunities to develop novel analysis tools.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005806","title":"HCA_Skin_Foetal_WSSS_RNA","description":"WSSS Deep Dive human foetal skin","abstract":"WSSS Deep dive - human foetal skin. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions. Data dissemination: We will submit any data generated from this project to the Human Cell Atlas data coordination platform (DCP). The DCP is hosted at EMBL-EBI, providing multiple cloud platforms to host the data and data portals that will ensure rapid open access to the scientific community and opportunities to develop novel analysis tools.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005807","title":"RNA-seq data from 27 glioblastoma samples","description":null,"abstract":"Glioblastoma (GBM) is an aggressive form of brain cancer with well-established patterns of intra-tumoral heterogeneity implicated in treatment resistance and progression. While regional and single cell transcriptomic variations of GBM have been recently resolved, downstream phenotype-level proteomic programs have yet to be assigned to specific niches. Here, we leverage mass spectrometry to spatially align abundance levels of 4,794 proteins to GBM’s hallmark histomorphologic niches across 20 patients and define distinct molecular programs operational within these regional tumor compartments.  Using machine learning, we overlay concordant transcriptional information, and define two distinct proteogenomic programs, MYC- and KRAS-axis hereon, that cooperate with hypoxia to produce a tri-dimensional model of intra-tumoral heterogeneity. Moreover, we highlight differential drug sensitivities and relative chemoresistance in GBM cell lines with enhanced KRAS programs. Importantly, pharmacological differences were less evident in transcriptional subgroups suggesting the proposed model may provide insights for targeting heterogeneity and overcoming therapy resistance in glioblastoma.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-19T16:02:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005808","title":"RNA sequencing data of in vitro differentiated megakaryocyte cells transduced with E527K and WT SRC","description":"For RNA sequencing (RNAseq), CD34+ hematopoietic stem cells (HSC) were isolated from healthy controls before transduction with WT-SRC and E527K-SRC lentiviral vectors in triplicate and differentiation to MK. RNA was extracted from the complete cell population as the aim was to detect differences in genes regulating MK maturation and differentiation. A total of six WT-SRC and six E527K-SRC RNA samples were used for RNAseq to identify differentially expressed genes.","abstract":"For RNA sequencing (RNAseq), CD34+ hematopoietic stem cells (HSC) were isolated from healthy controls before transduction with WT-SRC and E527K-SRC lentiviral vectors in triplicate and differentiation to MK. RNA was extracted from the complete cell population as the aim was to detect differences in genes regulating MK maturation and differentiation. A total of six WT-SRC and six E527K-SRC RNA samples were used for RNAseq to identify differentially expressed genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-19T16:05:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005809","title":"Proteomic profiling of human bone from different anatomical sites – A pilot study","description":null,"abstract":"The study aim is a comparative proteome-based analysis of different autologous bone entities (alveolar bone (AB), iliac cortical bone (IC) and iliac spongiosa (IS)) used for alveolar onlay grafting. This pilot study demonstrates an ECM protein-related proteome fingerprint in AB and an immune-related proteome fingerprint in IS and IC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005810","title":"Amplified EPOR/JAK2 genes define a unique subtype of acute erythroid leukemia","description":"Acute erythroid leukemia (AEL) is a unique subtype of acute myeloid leukemia characterized by prominent erythroid proliferation, whose molecular basis is poorly understood. To elucidate the underlying mechanism of erythroid proliferation, we performed comprehensive genomic study. The aim of this study is to unveil  genotype phenotype correlations and the feasible molecular targets for therapy of AEL.","abstract":"Acute erythroid leukemia (AEL) is a unique subtype of acute myeloid leukemia characterized by prominent erythroid proliferation, whose molecular basis is poorly understood. To elucidate the underlying mechanism of erythroid proliferation, we performed comprehensive genomic study. The aim of this study is to unveil  genotype phenotype correlations and the feasible molecular targets for therapy of AEL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-20T06:36:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005811","title":"Memory of stochastic single-cell apoptotic signalling promotes chemoresistance in neuroblastoma","description":"Gene expression noise is known to promote a non-genetic form of resistance in cancer cells through the elevated expression of specific genes within a stochastic population of rare cells. However, here we demonstrate that a much higher frequency population of chemoresistant neuroblastoma cells can arise when the influence of gene expression noise is integrated across multiple components of a signalling network. Using a c-Jun N-Terminal Kinase (JNK) activity biosensor with longitudinal high-content and in vivo intravital imaging, we reveal thestochasticity of chemotherapy-induced apoptotic signalling and confirm the existence of a population of JNK-impaired, chemoresistant cells that exist due to noise in components of this signalling network. Further, we demonstrate that a memory of this initially random resistant state is retained following treatment, achieved through maintenance of a repressive chromatin state. Using matched patient-derived xenograft models established at diagnosis and relapse from individual patients, we also demonstrate that priming neuroblastoma cells with a histone deacetylase inhibitor can restore drug-induced JNK activity within the chemoresistant population of treatment naïve tumours, but does not erase the memory of this resistant state from relapsed or refractory tumours.","abstract":"Gene expression noise is known to promote a non-genetic form of resistance in cancer cells through the elevated expression of specific genes within a stochastic population of rare cells. However, here we demonstrate that a much higher frequency population of chemoresistant neuroblastoma cells can arise when the influence of gene expression noise is integrated across multiple components of a signalling network. Using a c-Jun N-Terminal Kinase (JNK) activity biosensor with longitudinal high-content and in vivo intravital imaging, we reveal thestochasticity of chemotherapy-induced apoptotic signalling and confirm the existence of a population of JNK-impaired, chemoresistant cells that exist due to noise in components of this signalling network. Further, we demonstrate that a memory of this initially random resistant state is retained following treatment, achieved through maintenance of a repressive chromatin state. Using matched patient-derived xenograft models established at diagnosis and relapse from individual patients, we also demonstrate that priming neuroblastoma cells with a histone deacetylase inhibitor can restore drug-induced JNK activity within the chemoresistant population of treatment naïve tumours, but does not erase the memory of this resistant state from relapsed or refractory tumours.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005812","title":"Nanopore_and_Illumina_sequencing_of_human_glioblastomas","description":"Liquid biopsy analysis refers to methods designed to detect tumour-specific material (e.g., circulating tumour cells or tumour DNA) in body fluids, such as urine or blood samples. A widely-used liquid biopsy approach consists of genotyping the circulating tumour DNA (ctDNA) through sequencing of plasma/serum DNA.  Although useful in the context of metastatic disease (where the concentration of ctDNA is high), current liquid biopsy technologies show limited sensitivity of detection for the early detection of cancer, and low specificity, as cancer-related mutations accumulate in healthy tissues as part of the ageing process, thus making it difficult to distinguish these from tumour mutations, and because sequencing errors and true mutations show overlapping profiles.  Therefore, developing liquid biopsy protocols with increased sensitivity and specificity represents an urgent clinical need.\nHere we harness extrachromosomal circular DNA (eccDNA) elements, which are circular DNA structures physically separated from the chromosomes of up to several Mbp long pervasive in human cancers, for liquid biopsy analysis. In this pilot study we will focus on the analysis of glioblastomas, because there is strong evidence for the presence of eccDNA in these tumour types, and because developing liquid biopsy approaches for brain tumours to reduce the invasiveness of brain tumour biopsies remains an unmet clinical need.","abstract":"Liquid biopsy analysis refers to methods designed to detect tumour-specific material (e.g., circulating tumour cells or tumour DNA) in body fluids, such as urine or blood samples. A widely-used liquid biopsy approach consists of genotyping the circulating tumour DNA (ctDNA) through sequencing of plasma/serum DNA.  Although useful in the context of metastatic disease (where the concentration of ctDNA is high), current liquid biopsy technologies show limited sensitivity of detection for the early detection of cancer, and low specificity, as cancer-related mutations accumulate in healthy tissues as part of the ageing process, thus making it difficult to distinguish these from tumour mutations, and because sequencing errors and true mutations show overlapping profiles.  Therefore, developing liquid biopsy protocols with increased sensitivity and specificity represents an urgent clinical need.\nHere we harness extrachromosomal circular DNA (eccDNA) elements, which are circular DNA structures physically separated from the chromosomes of up to several Mbp long pervasive in human cancers, for liquid biopsy analysis. In this pilot study we will focus on the analysis of glioblastomas, because there is strong evidence for the presence of eccDNA in these tumour types, and because developing liquid biopsy approaches for brain tumours to reduce the invasiveness of brain tumour biopsies remains an unmet clinical need.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-22T10:17:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005813","title":"Nanopore_sequencing_of_human_glioblastomas","description":"Liquid biopsy analysis refers to methods designed to detect tumour-specific material (e.g., circulating tumour cells or tumour DNA) in body fluids, such as urine or blood samples. A widely-used liquid biopsy approach consists of genotyping the circulating tumour DNA (ctDNA) through sequencing of plasma/serum DNA.  Although useful in the context of metastatic disease (where the concentration of ctDNA is high), current liquid biopsy technologies show limited sensitivity of detection for the early detection of cancer, and low specificity, as cancer-related mutations accumulate in healthy tissues as part of the ageing process, thus making it difficult to distinguish these from tumour mutations, and because sequencing errors and true mutations show overlapping profiles.  Therefore, developing liquid biopsy protocols with increased sensitivity and specificity represents an urgent clinical need.\nHere we harness extrachromosomal circular DNA (eccDNA) elements, which are circular DNA structures physically separated from the chromosomes of up to several Mbp long pervasive in human cancers, for liquid biopsy analysis. In this pilot study we will focus on the analysis of glioblastomas, because there is strong evidence for the presence of eccDNA in these tumour types, and because developing liquid biopsy approaches for brain tumours to reduce the invasiveness of brain tumour biopsies remains an unmet clinical need.","abstract":"Liquid biopsy analysis refers to methods designed to detect tumour-specific material (e.g., circulating tumour cells or tumour DNA) in body fluids, such as urine or blood samples. A widely-used liquid biopsy approach consists of genotyping the circulating tumour DNA (ctDNA) through sequencing of plasma/serum DNA.  Although useful in the context of metastatic disease (where the concentration of ctDNA is high), current liquid biopsy technologies show limited sensitivity of detection for the early detection of cancer, and low specificity, as cancer-related mutations accumulate in healthy tissues as part of the ageing process, thus making it difficult to distinguish these from tumour mutations, and because sequencing errors and true mutations show overlapping profiles.  Therefore, developing liquid biopsy protocols with increased sensitivity and specificity represents an urgent clinical need.\nHere we harness extrachromosomal circular DNA (eccDNA) elements, which are circular DNA structures physically separated from the chromosomes of up to several Mbp long pervasive in human cancers, for liquid biopsy analysis. In this pilot study we will focus on the analysis of glioblastomas, because there is strong evidence for the presence of eccDNA in these tumour types, and because developing liquid biopsy approaches for brain tumours to reduce the invasiveness of brain tumour biopsies remains an unmet clinical need.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005814","title":"Macrophage migration inhibitory factor is overproduced through EGR1 in TET2low resting monocytes","description":null,"abstract":"Somatic mutation in TET2 gene is one of the most common clonal genetic events detected in age-related clonal hematopoiesis as well as in chronic myelomonocytic leukemia (CMML). In addition to being a pre-malignant state, TET2 mutated clones are associated with an increased risk of death from cardiovascular disease, which could involve cytokine/chemokine overproduction by monocytic cells. Here, we show in mice and in human cells that, in the absence of any inflammatory challenge, TET2 down-regulation promotes the production of MIF (macrophage migration inhibitory factor), a pivotal mediator of atherosclerotic lesion formation. In healthy monocytes, TET2 is recruited to MIF promoter and interacts with the transcription factor EGR1 and histone deacetylases. Disruption of these interactions as a consequence of TET2-decreased expression favors EGR1-driven transcription of MIF gene and its secretion. MIF favors monocytic differentiation of myeloid progenitors. These results designate MIF as a chronically overproduced chemokine and a potential therapeutic target in patients with clonal TET2 down-regulation in myeloid cells.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005815","title":"Sequencing data for CLL patients","description":"Single-cell RNA-sequencing and other genome-wide approaches were applied to a cohort of CLL patients receiving Venetoclax treatment to study mechanisms of resistance.","abstract":"Single-cell RNA-sequencing and other genome-wide approaches were applied to a cohort of CLL patients receiving Venetoclax treatment to study mechanisms of resistance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-24T03:56:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005816","title":"B cell receptor repertoire kinetics after SARS-CoV-2 infection and vaccination","description":"B cells play a central role in the immune response to both SARS-CoV-2 infection and vaccination, but the development of the B cell receptor (BCR) repertoire in both contexts has not been defined nor compared. We analysed serial samples from 171 SARS-CoV-2-infected individuals with a range of disease severities together with 63 vaccine recipients, and found marked differences in the global BCR repertoire after natural infection compared to vaccination. Following infection, the proportion of BCRs bearing IgG1/3 and IgA1 isotypes increased, somatic hypermutation (SHM) was markedly decreased and, in patients with severe disease, expansion of IgM and IgA clones was observed. In contrast, after vaccination the proportion of BCRs bearing IgD/M isotypes increased, SHM was unchanged and expansion of IgG clones was prominent. Infection generated a broad distribution of SARS-CoV-2-specific clones predicted to target the spike protein whilst vaccination produced a more focused response mainly targeting the spike’s receptor-binding domain. These findings offer insights into how different immune exposure to SARS-CoV-2 impacts upon BCR repertoire development, potentially informing vaccine strategies.","abstract":"B cells play a central role in the immune response to both SARS-CoV-2 infection and vaccination, but the development of the B cell receptor (BCR) repertoire in both contexts has not been defined nor compared. We analysed serial samples from 171 SARS-CoV-2-infected individuals with a range of disease severities together with 63 vaccine recipients, and found marked differences in the global BCR repertoire after natural infection compared to vaccination. Following infection, the proportion of BCRs bearing IgG1/3 and IgA1 isotypes increased, somatic hypermutation (SHM) was markedly decreased and, in patients with severe disease, expansion of IgM and IgA clones was observed. In contrast, after vaccination the proportion of BCRs bearing IgD/M isotypes increased, SHM was unchanged and expansion of IgG clones was prominent. Infection generated a broad distribution of SARS-CoV-2-specific clones predicted to target the spike protein whilst vaccination produced a more focused response mainly targeting the spike’s receptor-binding domain. These findings offer insights into how different immune exposure to SARS-CoV-2 impacts upon BCR repertoire development, potentially informing vaccine strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-24T13:01:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005817","title":"COVID_19_UK_CIC_Spatial","description":"Understanding the immune response to SARS-CoV-2 is critical to our ability to control the coronavirus pandemic. Spatial transcriptomics will be performed on COVID-19 post-mortem tissues in collaboration with the UK - Coronavirus Immunology Consortium (UK-CIC). UK-CIC encompasses a concerted effort by the UK's world-leading immunology community to deliver a co-ordinated and agile national research programme to increase our understanding of how the immune system interacts with SARS-CoV-2. UK-CIC is led by Professor Paul Moss (University of Birmingham) and brings together 20 UK immunology centres of excellence, with support from the British Society for Immunology.","abstract":"Understanding the immune response to SARS-CoV-2 is critical to our ability to control the coronavirus pandemic. Spatial transcriptomics will be performed on COVID-19 post-mortem tissues in collaboration with the UK - Coronavirus Immunology Consortium (UK-CIC). UK-CIC encompasses a concerted effort by the UK's world-leading immunology community to deliver a co-ordinated and agile national research programme to increase our understanding of how the immune system interacts with SARS-CoV-2. UK-CIC is led by Professor Paul Moss (University of Birmingham) and brings together 20 UK immunology centres of excellence, with support from the British Society for Immunology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-24T17:14:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005818","title":"Longitudinal single-cell transcriptomics reveals distinct patterns of recurrence in acute myeloid leukemia","description":null,"abstract":"Acute myeloid leukemia (AML) is a heterogeneous and aggressive blood cancer that results from diverse genetic aberrations in the hematopoietic stem or progenitor cells (HSPCs) leading to the expansion of blasts in the hematopoietic system. The heterogeneity and evolution of cancer blasts can render therapeutic interventions ineffective in a yet poorly understood patient-specific manner. To gain insight into the clonal heterogeneity of diagnosis (Dx) and relapse (Re) pairs, we employed whole exome sequencing and single-cell RNA-seq to longitudinally profile two t(8;21) (AML1-ETO = RUNX1-RUNX1T1), and four FLT3-ITD AML cases. \nThe single cell RNA data underpinned the tumor heterogeneity amongst patient blasts. The Dx-Re transcriptomes of high risk FLT3-ITD pairs formed a continuum from extensively changed in the absence of significantly mutational changes in AML-associated genes to rather similar Dx-Re pair of an intermediate risk FLT3-ITD. In one high risk FLT3-ITD pair, a pathway switched from an AP-1 regulated network in Dx to mTOR signaling in Re. The distinct Dx-Re AML1-ETO pairs comprise clusters that share genes related to hematopoietic stem cell maintenance and cell migration suggesting that the Re leukemic stem cell-like (LSC-like) cells probably evolved from the Dx LSC-like cells. \nIn summary, our study revealed a continuum from drastic transcriptional changes to extensive similarities between respective Dx-Re pairs that are poorly explained by the well-established model of clonal evolution. Our results suggest alternative and currently unappreciated and unexplored mechanisms that lead to therapeutic resistance and AML recurrence.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-26T15:33:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005819","title":"Longitudinal single-cell transcriptomics reveals distinct patterns of recurrence in acute myeloid leukemia","description":null,"abstract":"Acute myeloid leukemia (AML) is a heterogeneous and aggressive blood cancer that results from diverse genetic aberrations in the hematopoietic stem or progenitor cells (HSPCs) leading to the expansion of blasts in the hematopoietic system. The heterogeneity and evolution of cancer blasts can render therapeutic interventions ineffective in a yet poorly understood patient-specific manner. To gain insight into the clonal heterogeneity of diagnosis (Dx) and relapse (Re) pairs, we employed whole exome sequencing and single-cell RNA-seq to longitudinally profile two t(8;21) (AML1-ETO = RUNX1-RUNX1T1), and four FLT3-ITD AML cases. \nThe single cell RNA data underpinned the tumor heterogeneity amongst patient blasts. The Dx-Re transcriptomes of high risk FLT3-ITD pairs formed a continuum from extensively changed in the absence of significantly mutational changes in AML-associated genes to rather similar Dx-Re pair of an intermediate risk FLT3-ITD. In one high risk FLT3-ITD pair, a pathway switched from an AP-1 regulated network in Dx to mTOR signaling in Re. The distinct Dx-Re AML1-ETO pairs comprise clusters that share genes related to hematopoietic stem cell maintenance and cell migration suggesting that the Re leukemic stem cell-like (LSC-like) cells probably evolved from the Dx LSC-like cells. \nIn summary, our study revealed a continuum from drastic transcriptional changes to extensive similarities between respective Dx-Re pairs that are poorly explained by the well-established model of clonal evolution. Our results suggest alternative and currently unappreciated and unexplored mechanisms that lead to therapeutic resistance and AML recurrence.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-26T15:36:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005820","title":"Longitudinal single-cell transcriptomics reveals distinct patterns of recurrence in acute myeloid leukemia","description":null,"abstract":"Acute myeloid leukemia (AML) is a heterogeneous and aggressive blood cancer that results from diverse genetic aberrations in the hematopoietic stem or progenitor cells (HSPCs) leading to the expansion of blasts in the hematopoietic system. The heterogeneity and evolution of cancer blasts can render therapeutic interventions ineffective in a yet poorly understood patient-specific manner. To gain insight into the clonal heterogeneity of diagnosis (Dx) and relapse (Re) pairs, we employed whole exome sequencing and single-cell RNA-seq to longitudinally profile two t(8;21) (AML1-ETO = RUNX1-RUNX1T1), and four FLT3-ITD AML cases. \nThe single cell RNA data underpinned the tumor heterogeneity amongst patient blasts. The Dx-Re transcriptomes of high risk FLT3-ITD pairs formed a continuum from extensively changed in the absence of significantly mutational changes in AML-associated genes to rather similar Dx-Re pair of an intermediate risk FLT3-ITD. In one high risk FLT3-ITD pair, a pathway switched from an AP-1 regulated network in Dx to mTOR signaling in Re. The distinct Dx-Re AML1-ETO pairs comprise clusters that share genes related to hematopoietic stem cell maintenance and cell migration suggesting that the Re leukemic stem cell-like (LSC-like) cells probably evolved from the Dx LSC-like cells. \nIn summary, our study revealed a continuum from drastic transcriptional changes to extensive similarities between respective Dx-Re pairs that are poorly explained by the well-established model of clonal evolution. Our results suggest alternative and currently unappreciated and unexplored mechanisms that lead to therapeutic resistance and AML recurrence.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-26T15:39:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005821","title":"Clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancers defined by genomic analysis","description":"Ductal Carcinoma In Situ (DCIS) is the most common form of pre-invasive \nbreast cancer and despite treatment a small fraction (5-10%) of DCIS\npatients present with invasive disease many years later.  A fundamental\nbiologic question is whether the invasive disease recurring in the same\nbreast is established by  tumor cells in the initial DCIS or\nrepresents  new unrelated disease.  To address this question, we\nperformed genomic analyses on the initial pure DCIS lesion and paired\ninvasive recurrent tumors in 95 patients together with single cell DNA\nsequencing in a subset of cases.  Our data shows that in 75% the\ninvasive recurrence was clonally related to the initial DCIS,\nsuggesting that the tumor cells were not eliminated during the initial\ntreatment with surgery +/- radiotherapy. Surprisingly however, 18% were\nclonally unrelated to the DCIS, representing new independent lineages,\nand 7% of cases were ambiguous.  Our findings show that although DCIS\nis often the precursor of  invasive recurrence, a significant fraction\nof invasive recurrences are unrelated to the initial DCIS. This\nknowledge is essential for accurate risk evaluation of DCIS treatment\nde-escalation strategies and the identification of predictive\nbiomarkers.","abstract":"Ductal Carcinoma In Situ (DCIS) is the most common form of pre-invasive \nbreast cancer and despite treatment a small fraction (5-10%) of DCIS\npatients present with invasive disease many years later.  A fundamental\nbiologic question is whether the invasive disease recurring in the same\nbreast is established by  tumor cells in the initial DCIS or\nrepresents  new unrelated disease.  To address this question, we\nperformed genomic analyses on the initial pure DCIS lesion and paired\ninvasive recurrent tumors in 95 patients together with single cell DNA\nsequencing in a subset of cases.  Our data shows that in 75% the\ninvasive recurrence was clonally related to the initial DCIS,\nsuggesting that the tumor cells were not eliminated during the initial\ntreatment with surgery +/- radiotherapy. Surprisingly however, 18% were\nclonally unrelated to the DCIS, representing new independent lineages,\nand 7% of cases were ambiguous.  Our findings show that although DCIS\nis often the precursor of  invasive recurrence, a significant fraction\nof invasive recurrences are unrelated to the initial DCIS. This\nknowledge is essential for accurate risk evaluation of DCIS treatment\nde-escalation strategies and the identification of predictive\nbiomarkers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005822","title":"DNA sequencing for human normal endometrial glands","description":"To elucidate the timing and mechanism of the clonal expansion of somatic mutations in cancer-associated genes in the normal endometrium, we conducted whole-exome and whole-genome sequencing for 56 endometrial glands and matched blood samples from 4 women. By collecting endometrial glands from different parts of the endometrium, we showed that multiple glands with the same somatic mutations occupied substantial areas of the endometrium.","abstract":"To elucidate the timing and mechanism of the clonal expansion of somatic mutations in cancer-associated genes in the normal endometrium, we conducted whole-exome and whole-genome sequencing for 56 endometrial glands and matched blood samples from 4 women. By collecting endometrial glands from different parts of the endometrium, we showed that multiple glands with the same somatic mutations occupied substantial areas of the endometrium.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-29T08:49:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005823","title":"Clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancers defined by genomic analysis","description":"Ductal Carcinoma In Situ (DCIS) is the most common form of pre-invasive \nbreast cancer and despite treatment a small fraction (5-10%) of DCIS\npatients present with invasive disease many years later.  A fundamental\nbiologic question is whether the invasive disease recurring in the same\nbreast is established by  tumor cells in the initial DCIS or\nrepresents  new unrelated disease.  To address this question, we\nperformed genomic analyses on the initial pure DCIS lesion and paired\ninvasive recurrent tumors in 95 patients together with single cell DNA\nsequencing in a subset of cases.  Our data shows that in 75% the\ninvasive recurrence was clonally related to the initial DCIS,\nsuggesting that the tumor cells were not eliminated during the initial\ntreatment with surgery +/- radiotherapy. Surprisingly however, 18% were\nclonally unrelated to the DCIS, representing new independent lineages,\nand 7% of cases were ambiguous.  Our findings show that although DCIS\nis often the precursor of  invasive recurrence, a significant fraction\nof invasive recurrences are unrelated to the initial DCIS. This\nknowledge is essential for accurate risk evaluation of DCIS treatment\nde-escalation strategies and the identification of predictive\nbiomarkers.","abstract":"Ductal Carcinoma In Situ (DCIS) is the most common form of pre-invasive \nbreast cancer and despite treatment a small fraction (5-10%) of DCIS\npatients present with invasive disease many years later.  A fundamental\nbiologic question is whether the invasive disease recurring in the same\nbreast is established by  tumor cells in the initial DCIS or\nrepresents  new unrelated disease.  To address this question, we\nperformed genomic analyses on the initial pure DCIS lesion and paired\ninvasive recurrent tumors in 95 patients together with single cell DNA\nsequencing in a subset of cases.  Our data shows that in 75% the\ninvasive recurrence was clonally related to the initial DCIS,\nsuggesting that the tumor cells were not eliminated during the initial\ntreatment with surgery +/- radiotherapy. Surprisingly however, 18% were\nclonally unrelated to the DCIS, representing new independent lineages,\nand 7% of cases were ambiguous.  Our findings show that although DCIS\nis often the precursor of  invasive recurrence, a significant fraction\nof invasive recurrences are unrelated to the initial DCIS. This\nknowledge is essential for accurate risk evaluation of DCIS treatment\nde-escalation strategies and the identification of predictive\nbiomarkers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005824","title":"Clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancers defined by genomic analysis","description":"Ductal Carcinoma In Situ (DCIS) is the most common form of pre-invasive \nbreast cancer and despite treatment a small fraction (5-10%) of DCIS\npatients present with invasive disease many years later.  A fundamental\nbiologic question is whether the invasive disease recurring in the same\nbreast is established by  tumor cells in the initial DCIS or\nrepresents  new unrelated disease.  To address this question, we\nperformed genomic analyses on the initial pure DCIS lesion and paired\ninvasive recurrent tumors in 95 patients together with single cell DNA\nsequencing in a subset of cases.  Our data shows that in 75% the\ninvasive recurrence was clonally related to the initial DCIS,\nsuggesting that the tumor cells were not eliminated during the initial\ntreatment with surgery +/- radiotherapy. Surprisingly however, 18% were\nclonally unrelated to the DCIS, representing new independent lineages,\nand 7% of cases were ambiguous.  Our findings show that although DCIS\nis often the precursor of  invasive recurrence, a significant fraction\nof invasive recurrences are unrelated to the initial DCIS. This\nknowledge is essential for accurate risk evaluation of DCIS treatment\nde-escalation strategies and the identification of predictive\nbiomarkers.","abstract":"Ductal Carcinoma In Situ (DCIS) is the most common form of pre-invasive \nbreast cancer and despite treatment a small fraction (5-10%) of DCIS\npatients present with invasive disease many years later.  A fundamental\nbiologic question is whether the invasive disease recurring in the same\nbreast is established by  tumor cells in the initial DCIS or\nrepresents  new unrelated disease.  To address this question, we\nperformed genomic analyses on the initial pure DCIS lesion and paired\ninvasive recurrent tumors in 95 patients together with single cell DNA\nsequencing in a subset of cases.  Our data shows that in 75% the\ninvasive recurrence was clonally related to the initial DCIS,\nsuggesting that the tumor cells were not eliminated during the initial\ntreatment with surgery +/- radiotherapy. Surprisingly however, 18% were\nclonally unrelated to the DCIS, representing new independent lineages,\nand 7% of cases were ambiguous.  Our findings show that although DCIS\nis often the precursor of  invasive recurrence, a significant fraction\nof invasive recurrences are unrelated to the initial DCIS. This\nknowledge is essential for accurate risk evaluation of DCIS treatment\nde-escalation strategies and the identification of predictive\nbiomarkers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005825","title":"Clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancers defined by genomic analysis","description":"Ductal Carcinoma In Situ (DCIS) is the most common form of pre-invasive \nbreast cancer and despite treatment a small fraction (5-10%) of DCIS\npatients present with invasive disease many years later.  A fundamental\nbiologic question is whether the invasive disease recurring in the same\nbreast is established by  tumor cells in the initial DCIS or\nrepresents  new unrelated disease.  To address this question, we\nperformed genomic analyses on the initial pure DCIS lesion and paired\ninvasive recurrent tumors in 95 patients together with single cell DNA\nsequencing in a subset of cases.  Our data shows that in 75% the\ninvasive recurrence was clonally related to the initial DCIS,\nsuggesting that the tumor cells were not eliminated during the initial\ntreatment with surgery +/- radiotherapy. Surprisingly however, 18% were\nclonally unrelated to the DCIS, representing new independent lineages,\nand 7% of cases were ambiguous.  Our findings show that although DCIS\nis often the precursor of  invasive recurrence, a significant fraction\nof invasive recurrences are unrelated to the initial DCIS. This\nknowledge is essential for accurate risk evaluation of DCIS treatment\nde-escalation strategies and the identification of predictive\nbiomarkers.","abstract":"Ductal Carcinoma In Situ (DCIS) is the most common form of pre-invasive \nbreast cancer and despite treatment a small fraction (5-10%) of DCIS\npatients present with invasive disease many years later.  A fundamental\nbiologic question is whether the invasive disease recurring in the same\nbreast is established by  tumor cells in the initial DCIS or\nrepresents  new unrelated disease.  To address this question, we\nperformed genomic analyses on the initial pure DCIS lesion and paired\ninvasive recurrent tumors in 95 patients together with single cell DNA\nsequencing in a subset of cases.  Our data shows that in 75% the\ninvasive recurrence was clonally related to the initial DCIS,\nsuggesting that the tumor cells were not eliminated during the initial\ntreatment with surgery +/- radiotherapy. Surprisingly however, 18% were\nclonally unrelated to the DCIS, representing new independent lineages,\nand 7% of cases were ambiguous.  Our findings show that although DCIS\nis often the precursor of  invasive recurrence, a significant fraction\nof invasive recurrences are unrelated to the initial DCIS. This\nknowledge is essential for accurate risk evaluation of DCIS treatment\nde-escalation strategies and the identification of predictive\nbiomarkers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005826","title":"Failure of Differentiation of the Rhombic Lip Constitutes Medulloblastoma","description":"We used single-cell transcriptomics to study cells from the developing human cerebellum, and show that different molecular subgroups of medulloblastoma resemble distinct glutamatergic progenitors.","abstract":"We used single-cell transcriptomics to study cells from the developing human cerebellum, and show that different molecular subgroups of medulloblastoma resemble distinct glutamatergic progenitors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-29T15:06:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005827","title":"The evolutionary dynamics of human colorectal cancer using single-gland spatial multi-omic profiling of DNA, RNA and chromatin.","description":null,"abstract":"Deciphering the mechanisms of colorectal cancer growth, progression and dissemination in each individual patient,","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-29T16:40:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005828","title":"Molecular profiling of DLBCL patients treated in the PETAL trial","description":"Using whole-exome sequencing and shallow whole genome sequencing for simultaneous screening of mutations, copy number alterations, and translocations, 5 biology-based risk profiles could be reproduced in an independent cohort of DLBCL patients, from the PETAL trial.","abstract":"Using whole-exome sequencing and shallow whole genome sequencing for simultaneous screening of mutations, copy number alterations, and translocations, 5 biology-based risk profiles could be reproduced in an independent cohort of DLBCL patients, from the PETAL trial.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-29T17:00:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005829","title":"Whole exome sequencing of 12 NSCLC samples from 4 patients at MDACC","description":"Multi-region WES from 4 NSCLC patients, totaling 12 tumor samples and 4 matched control samples.","abstract":"Multi-region WES from 4 NSCLC patients, totaling 12 tumor samples and 4 matched control samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-29T18:31:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005830","title":"Full blood mRNA sequencing of myotonic dystrophy type 1 patients after cognitive behavioural therapy","description":"Myotonic dystrophy type 1 (DM1) is an incurable multisystem disease caused by a CTG-repeat expansion in the DM1 protein kinase (DMPK) gene. The OPTIMISTIC clinical trial demonstrated positive and heterogenous effects of cognitive behavioral therapy (CBT) on the capacity for activity and social participations in DM1 patients. Here, we performed mRNA sequencing of full blood for 27 patients of the OPTIMISTIC cohort before and after the CBT intervention. We identified 608 genes for which their expression was significantly associated with the disease causing CTG-repeat expansion, as well as with 1176 genes significantly associated with the average clinical response towards the intervention. Remarkably, all 97 genes significantly associated with both returned to more normal levels in patients who benefited most from CBT. This trend was consistent with the difference observed between DM1 patients and controls in an earlier study of blood mRNA expression levels, singling these genes out as candidate biomarkers for therapy response. Together these results highlight the ability to find disease relevant information in full blood of DM1 patients and  open new avenues to monitor therapy effects.","abstract":"Myotonic dystrophy type 1 (DM1) is an incurable multisystem disease caused by a CTG-repeat expansion in the DM1 protein kinase (DMPK) gene. The OPTIMISTIC clinical trial demonstrated positive and heterogenous effects of cognitive behavioral therapy (CBT) on the capacity for activity and social participations in DM1 patients. Here, we performed mRNA sequencing of full blood for 27 patients of the OPTIMISTIC cohort before and after the CBT intervention. We identified 608 genes for which their expression was significantly associated with the disease causing CTG-repeat expansion, as well as with 1176 genes significantly associated with the average clinical response towards the intervention. Remarkably, all 97 genes significantly associated with both returned to more normal levels in patients who benefited most from CBT. This trend was consistent with the difference observed between DM1 patients and controls in an earlier study of blood mRNA expression levels, singling these genes out as candidate biomarkers for therapy response. Together these results highlight the ability to find disease relevant information in full blood of DM1 patients and  open new avenues to monitor therapy effects.","study_type":"Other","pubmed_ids":[29934199],"external_links":null,"is_released":true,"released_date":"2021-11-29T20:45:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005831","title":"H3Africa - HIGeneS Africa","description":"HiGENES Africa (Hearing Impairment Genetic Studies in Africa), we propose to use whole exome sequencing (WES), to study the largest sample of sub-Saharan Africans from Cameroon, Mali, Ghana, and South Africa with prelingual non-syndromic hearing impairment (NSHI), in order to identify novel NSHI genes and to better understand the genetic etiology of NSHI in African populations. We will also engage policies makers, and support groups on psychosocial challenges experienced by families and people living with HI. HIGENES Africa has high public health significance, since it will add on global knowledge, and specifically improve genetic diagnosis, and future prediction of treatment outcomes in sub-Saharan Africans, and people of African descent.","abstract":"HiGENES Africa (Hearing Impairment Genetic Studies in Africa), we propose to use whole exome sequencing (WES), to study the largest sample of sub-Saharan Africans from Cameroon, Mali, Ghana, and South Africa with prelingual non-syndromic hearing impairment (NSHI), in order to identify novel NSHI genes and to better understand the genetic etiology of NSHI in African populations. We will also engage policies makers, and support groups on psychosocial challenges experienced by families and people living with HI. HIGENES Africa has high public health significance, since it will add on global knowledge, and specifically improve genetic diagnosis, and future prediction of treatment outcomes in sub-Saharan Africans, and people of African descent.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005832","title":"DNA methylation analysis on PBL obtained from male patients with UC-PSC, UC and HC","description":"Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease affecting the intra- and extrahepatic bile ducts, and is strongly associated with ulcerative colitis (UC). In this study, we explored the peripheral blood DNA methylome and its immune cell composition in patients with PSC-UC, UC, and healthy controls (HC) with the aim to develop a predictive assay in distinguishing patients with PSC-UC from those with UC alone.\n\nThe peripheral blood DNA methylome of male patients with PSC and concomitant UC, UC and HCs was profiled using the Illumina HumanMethylation Infinium EPIC BeadChip (850K) array. Differentially methylated CpG position (DMP) and region (DMR) analyses were performed alongside gradient boosting classification analyses to discern PSC-UC from UC patients. As observed differences in the DNA methylome could be the result of differences in cellular populations, we additionally employed mass cytometry to characterize the immune cell compositions. \n\nGenome wide methylation analysis revealed no differentially methylated positions between PSC-UC and UC patients. Nonetheless, using gradient boosting we were capable of discerning PSC-UC from UC with an area under the receiver operator curve (AUROC) of 0.80. Four CpG sites annotated to the NINJ2 gene were found to strongly contribute to the predictive performance. While mass cytometry analyses corroborated the largely similar blood cell composition among patients with PSC-UC, UC and HC, a higher abundance of myeloid cells was observed in UC compared to PSC-UC patients.","abstract":"Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease affecting the intra- and extrahepatic bile ducts, and is strongly associated with ulcerative colitis (UC). In this study, we explored the peripheral blood DNA methylome and its immune cell composition in patients with PSC-UC, UC, and healthy controls (HC) with the aim to develop a predictive assay in distinguishing patients with PSC-UC from those with UC alone.\n\nThe peripheral blood DNA methylome of male patients with PSC and concomitant UC, UC and HCs was profiled using the Illumina HumanMethylation Infinium EPIC BeadChip (850K) array. Differentially methylated CpG position (DMP) and region (DMR) analyses were performed alongside gradient boosting classification analyses to discern PSC-UC from UC patients. As observed differences in the DNA methylome could be the result of differences in cellular populations, we additionally employed mass cytometry to characterize the immune cell compositions. \n\nGenome wide methylation analysis revealed no differentially methylated positions between PSC-UC and UC patients. Nonetheless, using gradient boosting we were capable of discerning PSC-UC from UC with an area under the receiver operator curve (AUROC) of 0.80. Four CpG sites annotated to the NINJ2 gene were found to strongly contribute to the predictive performance. While mass cytometry analyses corroborated the largely similar blood cell composition among patients with PSC-UC, UC and HC, a higher abundance of myeloid cells was observed in UC compared to PSC-UC patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-30T08:35:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005833","title":"Paired data of primary and relapse central nervous system lymphoma and  testicular lymphoma","description":"Shallow whole genome sequencing and targeted sequencing of 33 primary - relapse samplepairs of primary central nervous system lymphoma and primary testicular lymphoma.19 Testis - contralateral testis pairs9 Testis - CNS 5 CNS - Testis","abstract":"Shallow whole genome sequencing and targeted sequencing of 33 primary - relapse samplepairs of primary central nervous system lymphoma and primary testicular lymphoma.19 Testis - contralateral testis pairs9 Testis - CNS 5 CNS - Testis","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-30T09:26:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005834","title":"NLG-LBC-05 Trial ctDNA","description":null,"abstract":"Correlative analysis of circulating tumor DNA (ctDNA) in aggressive large B-cell lymphoma patients treated in NLG-LBC-05 phase II trial. Whole genome and targeted sequencing was applied to longitudinal plasma cell-free DNA and diagnostic tumor tissues.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005835","title":"NLG-LBC-05 ctDNA","description":"Correlative analysis of circulating tumor DNA (ctDNA) in aggressive large B-cell lymphoma patients treated in NLG-LBC-05 phase II trial. Whole genome and targeted sequencing was applied to longitudinal plasma cell-free DNA and diagnostic tumor tissues.","abstract":"Correlative analysis of circulating tumor DNA (ctDNA) in aggressive large B-cell lymphoma patients treated in NLG-LBC-05 phase II trial. Whole genome and targeted sequencing was applied to longitudinal plasma cell-free DNA and diagnostic tumor tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-11-30T16:53:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005836","title":"Gene expression-based prediction of pazopanib efficacy in sarcoma (HIPO, H021)","description":"The multi-receptor tyrosine kinase (RTK) inhibitor pazopanib is approved for the treatment of advanced non-adipocytic soft-tissue sarcoma and has also shown activity in other sarcoma subtypes. However, its clinical efficacy is highly variable, and no reliable predictors exist to date to select patients who are most likely to benefit from this drug. We analyzed the molecular profiles and clinical outcomes of pazopanib-treated sarcoma patients enrolled in a prospective observational study by the German Cancer Consortium, DKTK MASTER, that employs whole-genome/exome sequencing (WGS/WES) and transcriptome sequencing to inform the care of adults with advanced cancer across histologies who are younger than 51 and patients with rare tumors, including rare subtypes of more common entities, regardless of age.​ Among a total of 109 patients with available WGS/WES data, there was no correlation between clinical parameters, specific genetic alterations, or mutational signatures and clinical outcome. In contrast, analysis of a subcohort of 62 patients who underwent molecular analysis before pazopanib treatment and had transcriptome sequencing data available showed that mRNA levels of NTRK3 (hazard ratio [HR]=0.53, p=0.021), IGF1R (HR=1.82, p=0.027), and KDR (HR=0.50, p=0.011) were independently associated with progression-free survival (PFS). Based on the expression of these RTK genes, i.e., the features NTRK3-high, IGF1R-low, and KDR-high, we developed a pazopanib efficacy predictor (PEP) that stratified patients into three groups with significantly different PFS (p&lt;0.0001). Application of the PEP to an independent cohort of pazopanib-treated sarcoma patients from DKTK MASTER (n=43) confirmed its potential to separate patient groups with significantly different PFS (p=0.02), whereas no such association was observed in sarcoma patients from DKTK MASTER (n=77) or The Cancer Genome Atlas sarcoma cohort (n=256) who were not treated with pazopanib. A score based on the combined expression of NTRK3, IGF1R, and KDR allows identification of sarcoma patients with good, intermediate, and poor outcome following pazopanib therapy and warrants investigation as a predictive tool in prospective studies to optimize the use of this drug in the clinic.","abstract":"The multi-receptor tyrosine kinase (RTK) inhibitor pazopanib is approved for the treatment of advanced non-adipocytic soft-tissue sarcoma and has also shown activity in other sarcoma subtypes. However, its clinical efficacy is highly variable, and no reliable predictors exist to date to select patients who are most likely to benefit from this drug. We analyzed the molecular profiles and clinical outcomes of pazopanib-treated sarcoma patients enrolled in a prospective observational study by the German Cancer Consortium, DKTK MASTER, that employs whole-genome/exome sequencing (WGS/WES) and transcriptome sequencing to inform the care of adults with advanced cancer across histologies who are younger than 51 and patients with rare tumors, including rare subtypes of more common entities, regardless of age.​ Among a total of 109 patients with available WGS/WES data, there was no correlation between clinical parameters, specific genetic alterations, or mutational signatures and clinical outcome. In contrast, analysis of a subcohort of 62 patients who underwent molecular analysis before pazopanib treatment and had transcriptome sequencing data available showed that mRNA levels of NTRK3 (hazard ratio [HR]=0.53, p=0.021), IGF1R (HR=1.82, p=0.027), and KDR (HR=0.50, p=0.011) were independently associated with progression-free survival (PFS). Based on the expression of these RTK genes, i.e., the features NTRK3-high, IGF1R-low, and KDR-high, we developed a pazopanib efficacy predictor (PEP) that stratified patients into three groups with significantly different PFS (p&lt;0.0001). Application of the PEP to an independent cohort of pazopanib-treated sarcoma patients from DKTK MASTER (n=43) confirmed its potential to separate patient groups with significantly different PFS (p=0.02), whereas no such association was observed in sarcoma patients from DKTK MASTER (n=77) or The Cancer Genome Atlas sarcoma cohort (n=256) who were not treated with pazopanib. A score based on the combined expression of NTRK3, IGF1R, and KDR allows identification of sarcoma patients with good, intermediate, and poor outcome following pazopanib therapy and warrants investigation as a predictive tool in prospective studies to optimize the use of this drug in the clinic.","study_type":"Other","pubmed_ids":[35763870],"external_links":null,"is_released":true,"released_date":"2021-11-30T17:30:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005837","title":"Microbiota-Directed Food Intervention for Undernourished Children","description":null,"abstract":"BACKGROUND\nMore than 30 million children worldwide have moderate acute malnutrition. Current treatments have limited effectiveness, and much remains unknown about the pathogenesis of this condition. Children with moderate acute malnutrition have perturbed development of their gut microbiota.\n\nMETHODS\nIn this study, we provided a microbiota-directed complementary food prototype (MDCF-2) or a ready-to-use supplementary food (RUSF) to 123 slum-dwelling Bangladeshi children with moderate acute malnutrition between the ages of 12 months and 18 months. The supplementation was given twice daily for 3 months, followed by 1 month of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age z scores and mid–upper-arm circumference values at baseline and every 2 weeks during the intervention period and at 4 months. We compared the rate of change of these related phenotypes between baseline and 3 months and between baseline and 4 months. We also measured levels of 4977 proteins in plasma and 209 bacterial taxa in fecal samples.\n\nRESULTS\nA total of 118 children (59 in each study group) completed the intervention. The rates of change in the weight-for-length and weight-for-age z scores are consistent with a benefit of MDCF-2 on growth over the course of the study, including the 1-month follow-up. Receipt of MDCF-2 was linked to the magnitude of change in levels of 70 plasma proteins and of 21 associated bacterial taxa that were positively correlated with the weight-for-length z score (P&lt;0.001 for comparisons of both protein and bacterial taxa). These proteins included mediators of bone growth and neurodevelopment.\n\nCONCLUSIONS\nThese findings provide support for MDCF-2 as a dietary supplement for young children with moderate acute malnutrition and provide insight into mechanisms by which this targeted manipulation of microbiota components may be linked to growth.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005838","title":"Whole Exome Sequencing of Bipolar cases and matched controls performed at the Broad Institute on a cohort from Landen, Stockholm, Sweden.","description":null,"abstract":"The Bipolar Exome (BipEx) collaboration analysis of whole exome sequencing of individuals diagnosed with bipolar disorder (BD), matched with controls. We found an excess of ultra-rare protein-truncating variants (PTVs) in BD patients among genes under strong evolutionary constraint, a signal evident in both major BD subtypes, bipolar 1 disorder (BD1) and bipolar 2 disorder (BD2).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-05-16T16:36:08.692189+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005839","title":"Genome-wide Rare Variant Score Associates With Morphological Subtypes of Autism Spectrum Disorder","description":null,"abstract":"Defining different genetic subtypes of Autism Spectrum Disorder (ASD) can help predict developmental outcomes. Based on minor physical and major congenital anomalies, we categorized 325 Canadian children with ASD into dysmorphic and non-dysmorphic subgroupings. We developed a method to calculate a genome-wide rare variant score (GRVS) from whole-genome sequencing (WGS) data for each ASD proband. GRVS is a sum of the number of variants in morphology-associated coding and non-coding regions, weighted by their effect sizes. Probands with dysmorphic ASD had a significantly higher GRVS compared to those with non-dysmorphic ASD (P= 0.027). Using the polygenic transmission disequilibrium test, we observed an over-transmission of ASD-associated common variants in non-dysmorphic ASD probands (P= 2.9 x 10-3). We replicated our findings using 442 ASD probands that had accompanying morphology data in the Simons Simplex Collection. Our findings provide support for an alternative genomic classification of ASD subgroups using morphology data, which may inform intervention protocols.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005840","title":"SPECTA RP-1759-AYA Sarcoma cohort","description":"EORTC-SPECTA RP1759 study focuses on cancers in adolescent and young adult (AYA), age 12 to 29 years. This study explicitly recruited AYA patients and therefore collected empirical data to bridge the molecular gap between pediatric and adult oncology.\nThe initial pilot study, activated in February 2019 across Europe, aimed to recruit 100 AYA patients (aged 12-29 years) with newly diagnosed or relapsed high-grade gliomas and high-grade bone and soft tissue sarcomas. The primary objective of the pilot is to determine feasibility and recruitment rates.\nHere we submit the data from patients with newly diagnosed, recurrent intermediate or high-grade sarcoma that were collected and analyzed during the study. More specifically, we submit raw FASTQ files obtained from whole exome sequencing (WES) of matching tumor and blood samples, tumor RNA sequencing and DNA methylation profiling.","abstract":"EORTC-SPECTA RP1759 study focuses on cancers in adolescent and young adult (AYA), age 12 to 29 years. This study explicitly recruited AYA patients and therefore collected empirical data to bridge the molecular gap between pediatric and adult oncology.\nThe initial pilot study, activated in February 2019 across Europe, aimed to recruit 100 AYA patients (aged 12-29 years) with newly diagnosed or relapsed high-grade gliomas and high-grade bone and soft tissue sarcomas. The primary objective of the pilot is to determine feasibility and recruitment rates.\nHere we submit the data from patients with newly diagnosed, recurrent intermediate or high-grade sarcoma that were collected and analyzed during the study. More specifically, we submit raw FASTQ files obtained from whole exome sequencing (WES) of matching tumor and blood samples, tumor RNA sequencing and DNA methylation profiling.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-02T14:46:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005841","title":"Whole Exome Sequencing of Bipolar cases and matched controls performed at the Broad Institute on a cohort from KI, Sweden.","description":null,"abstract":"Bipolar Exome (BipEx) collaboration analysis of whole exome sequencing of individuals diagnosed with bipolar disorder (BD), and matched  controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in BD patients among genes under strong evolutionary constraint, a signal evident in both major BD subtypes, bipolar 1 disorder (BD1) and bipolar 2 disorder (BD2).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005842","title":"Whole Exome Sequencing of Bipolar cases and matched controls performed at the Broad Institute on a cohort from Umea, Sweden.","description":null,"abstract":"Bipolar Exome (BipEx) collaboration analysis of whole exome sequencing of individuals diagnosed with bipolar disorder (BD), and matched  controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in BD patients among genes under strong evolutionary constraint, a signal evident in both major BD subtypes, bipolar 1 disorder (BD1) and bipolar 2 disorder (BD2).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-05-22T10:35:21.32936+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005843","title":"Whole Exome Sequencing of Bipolar cases and matched controls performed at the Broad Institute on a cohort from Edinburgh, Scotland, UK.","description":null,"abstract":"Bipolar Exome (BipEx) collaboration analysis of whole exome sequencing of individuals diagnosed with bipolar disorder (BD), and matched  controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in BD patients among genes under strong evolutionary constraint, a signal evident in both major BD subtypes, bipolar 1 disorder (BD1) and bipolar 2 disorder (BD2).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-07-26T18:10:14.860579+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005844","title":"Whole Exome Sequencing of Bipolar cases and matched controls performed at the Broad Institute on a cohort from Dublin, Ireland.","description":null,"abstract":"Bipolar Exome (BipEx) collaboration analysis of whole exome sequencing of individuals diagnosed with bipolar disorder (BD), and matched  controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in BD patients among genes under strong evolutionary constraint, a signal evident in both major BD subtypes, bipolar 1 disorder (BD1) and bipolar 2 disorder (BD2).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-04-03T14:47:52.790386+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005845","title":"Whole Exome Sequencing of Bipolar cases and controls performed at the Broad Institute on a cohort from Cardiff, UK (Craddock)","description":null,"abstract":"Bipolar Exome (BipEx) collaboration analysis of whole exome sequencing of individuals diagnosed with bipolar disorder (BD), and matched  controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in BD patients among genes under strong evolutionary constraint, a signal evident in both major BD subtypes, bipolar 1 disorder (BD1) and bipolar 2 disorder (BD2).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-06-17T16:31:10.499212+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005846","title":"Orthotopic murine Group 3 medulloblastoma in C57Bl/6 mice treated with saline, cyclophosphamide or gemcitabine","description":null,"abstract":"tba","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-03T05:52:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005847","title":"Orthotopic murine Group 3 medulloblastoma in C57Bl/6 mice treated with sham or craniospinal irradiation","description":null,"abstract":"tba","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-03T05:52:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005848","title":"Searching for genetic modulators of the phenotypic heterogeneity in Brugada Syndrome","description":null,"abstract":"In Brugada syndrome, even within the same family where all affected individuals share\nthe same mutation, phenotypic variation is prominent, with variable penetrance and\nexpressivity, presenting different degrees of involvement. It is difficult to establish a\ndirect correlation between genotype and phenotype to predict prognosis in\ncomplications and risk of sudden death. The factors that modulate this inter- and intrafamilial\nphenotypic variability remain to be determined. With the intention of testing\nwhether other genetic factors, in addition to the causal mutation in SCN5A , may have\na modulating effect on the Brugada phenotype and the risk of sudden death, we have\nstudied 8 families with a causal variant in SCN5A with at least two affected individuals,\none of whom has suffered cardiac arrest or sudden death. Whole exome sequencing\nwas performed looking for additional variants that modify the phenotype and allow us\nto predict a better or worse prognosis for the evolution of the disease. The results did\nnot show any clear genetic modifier; nevertheless, highlight the possible implication of\nthe cholesterol and fibrosis pathways, as well as the circadian rhythm, as possible\nmodulators of Brugada syndrome phenotype.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-03T08:40:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005849","title":"Optimisation of CITE-seq on liquid and solid tissues","description":null,"abstract":"While great efforts are being made to establish single-cell transcriptomics profiling of clinical material, protein expression of clinically relevant biomarkers has been harder to integrate into existing pipelines. CITE-seq bridges the RNA-protein gap, but has so far primarily been applied to liquid biopsies, which do not require tissue dissociation. Processing of solid biopsies to characterize the tumor microenvironment is an essential next step in applying single-cell technologies to translational studies. Here, we demonstrate CITE-seq performance and protocol customizations on dissociated tissues such as human skin and primary and metastatic melanoma biopsies on a total of 52,672 cells from 11 solid and 6 liquid primary samples. Analogous to fluorescently activated cell sorting (FACS), we describe gating of cell populations based on transcriptome signatures and setting thresholds for protein expression using cell type-aware ridge plot visualization. For a panel of 97 antibodies, we report on gene and protein expression correlation in liquid and solid sample cohorts. Using peripheral blood mononuclear cells (PBMCs) as a model, we show the effect of enzymatic digestion on transcriptome and epitope expression in immune cell populations. Additionally, we optimized digestion protocols for healthy skin and tumor tissues that yield various cell populations within a given tissue type. Finally, we demonstrate the applicability of CITE-seq for biomarker discovery on metastatic melanoma. Our work provides a blueprint and pipeline for CITE-seq to a broad range of clinically relevant samples, thus allowing for an increasingly detailed resolution of solid tissue specimens and enabling translational studies where protein biomarker profiling could provide better functional descriptions of cell states. We believe that the described protocol will find wide-ranging applications for basic and clinical research.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-03T11:55:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005850","title":"TB-DAR Whole Genome Sequencing Study","description":"116 Whole Genome Sequencing (WGS) samples from the TB-DAR study, which consists of a cohort of adult pulmonary tuberculosis patients recruited in Dar es Salaam, Tanzania.","abstract":"116 Whole Genome Sequencing (WGS) samples from the TB-DAR study, which consists of a cohort of adult pulmonary tuberculosis patients recruited in Dar es Salaam, Tanzania.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-03T17:00:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005851","title":"Whole Exome Sequencing of Bipolar cases and matched controls performed at the Broad Institute on a cohort from London, UK","description":null,"abstract":"Bipolar Exome (BipEx) collaboration analysis of whole exome sequencing of individuals diagnosed with bipolar disorder (BD), and matched  controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in BD patients among genes under strong evolutionary constraint, a signal evident in both major BD subtypes, bipolar 1 disorder (BD1) and bipolar 2 disorder (BD2).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-12-11T15:12:55.29595+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005852","title":"Whole Exome Sequencing of Bipolar cases and matched controls performed at the Broad Institute on a cohort from Cardiff, UK (O'Donovan)","description":null,"abstract":"Bipolar Exome (BipEx) collaboration analysis of whole exome sequencing of individuals diagnosed with bipolar disorder (BD), and matched  controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in BD patients among genes under strong evolutionary constraint, a signal evident in both major BD subtypes, bipolar 1 disorder (BD1) and bipolar 2 disorder (BD2).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-10-31T12:55:39.963593+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005853","title":"Whole Exome Sequencing of Bipolar cases and matched controls performed at the Broad Institute on a cohort from the Netherlands (Ophoff)","description":null,"abstract":"Abstract:\nBipolar Exome (BipEx) collaboration analysis of whole exome sequencing of individuals diagnosed with bipolar disorder (BD), and matched  controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in BD patients among genes under strong evolutionary constraint, a signal evident in both major BD subtypes, bipolar 1 disorder (BD1) and bipolar 2 disorder (BD2).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-12-09T12:45:47.018825+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005854","title":"Whole Exome Sequencing of Bipolar cases and matched controls performed at the Broad Institute on a cohort from Cambridge, UK","description":null,"abstract":"Abstract:\nBipolar Exome (BipEx) collaboration analysis of whole exome sequencing of individuals diagnosed with bipolar disorder (BD), and matched  controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in BD patients among genes under strong evolutionary constraint, a signal evident in both major BD subtypes, bipolar 1 disorder (BD1) and bipolar 2 disorder (BD2).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-08-13T13:45:40.160317+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005855","title":"Whole Exome Sequencing of Bipolar cases and matched controls performed at the Broad Institute on a cohort from Cardiff, UK (Owen)","description":null,"abstract":"Bipolar Exome (BipEx) collaboration analysis of whole exome sequencing of individuals diagnosed with bipolar disorder (BD), and matched  controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in BD patients among genes under strong evolutionary constraint, a signal evident in both major BD subtypes, bipolar 1 disorder (BD1) and bipolar 2 disorder (BD2).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-10-13T09:43:43.606977+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005856","title":"Whole Exome Sequencing of Bipolar cases and matched controls performed at the Broad Institute on a cohort from Stockholm, Sweden (Pedersen)","description":null,"abstract":"Bipolar Exome (BipEx) collaboration analysis of whole exome sequencing of individuals diagnosed with bipolar disorder (BD), and matched  controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in BD patients among genes under strong evolutionary constraint, a signal evident in both major BD subtypes, bipolar 1 disorder (BD1) and bipolar 2 disorder (BD2).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-12-30T10:56:23.186664+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005857","title":"Whole Exome Sequencing of Bipolar cases and matched controls performed at the Broad Institute on a cohort from the Netherlands (posthuma)","description":null,"abstract":"Bipolar Exome (BipEx) collaboration analysis of whole exome sequencing of individuals diagnosed with bipolar disorder (BD), and matched  controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in BD patients among genes under strong evolutionary constraint, a signal evident in both major BD subtypes, bipolar 1 disorder (BD1) and bipolar 2 disorder (BD2).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-07-18T16:58:25.227492+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005858","title":"Whole Exome Sequencing of Bipolar cases and matched controls performed at the Broad Institute on a cohort from Germany","description":null,"abstract":"Bipolar Exome (BipEx) collaboration analysis of whole exome sequencing of individuals diagnosed with bipolar disorder (BD), and matched  controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in BD patients among genes under strong evolutionary constraint, a signal evident in both major BD subtypes, bipolar 1 disorder (BD1) and bipolar 2 disorder (BD2).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-06-13T13:40:45.266563+02:00","is_deprecated":false},
{"accession_id":"EGAS00001005859","title":"Whole Exome Sequencing of Bipolar cases and matched controls performed at the Broad Institute on a cohort from Aberdeen, Scotland, UK","description":null,"abstract":"Bipolar Exome (BipEx) collaboration analysis of whole exome sequencing of individuals diagnosed with bipolar disorder (BD), and matched  controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in BD patients among genes under strong evolutionary constraint, a signal evident in both major BD subtypes, bipolar 1 disorder (BD1) and bipolar 2 disorder (BD2).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005860","title":"Swedish Bipolar Disorder exome sequencing (SWEBIC)","description":null,"abstract":"Swedish Bipolar Disorder exome sequencing","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-01-09T16:17:33.847421+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005861","title":"Single-nuclei gene-expression analysis of pheochromocytoma and paraganglioma links tumor subtypes with tumor microenvironment","description":"Pheochromocytomas and paragangliomas (PCPG) are rare neuroendocrine tumors associated with autonomic nerves. We used single nuclei-RNA-seq (snRNA-seq) for analysis of 30 PCPG representing 13 known driver genes, plus two normal adrenal medullas to dissect cell composition, refine PCPG subtypes and compare PCPG and normal tissue expression. Incorporating bulk-tissue and snRNA-seq data we identified seven PCPG gene-expression subtypes with genotype and cell type associations. The tumor microenvironment reflected HIF pathway activation and neovascularization by detection of abundant tip-like endothelial cells and pericytes concordant with VEGFA expression in neoplastic cells with mutations in VHL, genes encoding SDH subunits and MAML3-fusions. Macrophages were abundant in PCPG with distinct tumor-associated features. Schwann-cell-like cells were also enriched in some subtypes. The transcriptional profile of neoplastic PCPG cells resembled normal chromaffin cells but early chromaffin and neuroblast cell markers were expressed in some subtypes including GPR139, a putative therapeutic target for a subset of pseudohypoxic PCPG.","abstract":"Pheochromocytomas and paragangliomas (PCPG) are rare neuroendocrine tumors associated with autonomic nerves. We used single nuclei-RNA-seq (snRNA-seq) for analysis of 30 PCPG representing 13 known driver genes, plus two normal adrenal medullas to dissect cell composition, refine PCPG subtypes and compare PCPG and normal tissue expression. Incorporating bulk-tissue and snRNA-seq data we identified seven PCPG gene-expression subtypes with genotype and cell type associations. The tumor microenvironment reflected HIF pathway activation and neovascularization by detection of abundant tip-like endothelial cells and pericytes concordant with VEGFA expression in neoplastic cells with mutations in VHL, genes encoding SDH subunits and MAML3-fusions. Macrophages were abundant in PCPG with distinct tumor-associated features. Schwann-cell-like cells were also enriched in some subtypes. The transcriptional profile of neoplastic PCPG cells resembled normal chromaffin cells but early chromaffin and neuroblast cell markers were expressed in some subtypes including GPR139, a putative therapeutic target for a subset of pseudohypoxic PCPG.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-06T07:51:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005862","title":"Comprehensive characterization of pre- and post-treatment samples of breast cancer reveal potential mechanisms of chemotherapy resistance","description":null,"abstract":"When locally advanced breast cancer is treated with neoadjuvant chemotherapy, the recurrence risk is significantly higher if no complete pathologic response is achieved. Identification of the underlying resistance mechanisms is essential to select treatments with maximal efficacy and minimal toxicity. Here we employed gene expression profiles derived from 317 HER2-negative treatment-naïve breast cancer biopsies of patients who underwent neoadjuvant chemotherapy, deep whole exome and RNA-sequencing profiles of 22 matched pre- and post-treatment tumors, and treatment outcome data to identify biomarkers of response and resistance mechanisms. Molecular profiling of treatment-naïve breast cancer samples revealed that expression levels of proliferation, immune response and extracellular matrix (ECM) organization combined predict response to chemotherapy. Triple negative patients with high proliferation, high immune response and low ECM expression had a significantly better treatment response and survival benefit (HR 0.29, 95% CI 0.10-0.85; p=0.02), while in ER+ patients the opposite was seen (HR 4.73, 95% CI 1.51-14.8; 0=0.008). The characterization of paired pre-and post-treatment samples revealed that aberrations of known cancer genes were either only present in the pre-treatment sample (CDKN1B) or in the post-treatment sample(TP53, APC, CTNNB1). Proliferation-associated genes were frequently down-regulated in post-treatment ER+ tumors, but not in triple negative tumors. Genes involved in ECM were upregulated in the majority of post-chemotherapy samples. Genomic and transcriptomic differences between pre- and post-chemotherapy samples are common and may reveal potential mechanisms of therapy resistance. Our results show a wide range of distinct, but related mechanisms, with a prominent role for proliferation- and ECM-related genes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005863","title":"Identification of the dismal subtype of B-ALL with dysregulation of CDX2 and UBTF","description":"PURPOSE: Advance in the knowledge of genomic basis of B-cell acute lymphoblastic leukemia (B-ALL) has changed the treatment approaches and diagnostic assays and improved their outcome. Despite the recent development of next generation sequencing approaches, there are still some cases that their drivers are unknown. We aimed to define and describe the characteristics of an additional B-ALL subtype by integrating genomic, transcriptomic, and epigenomic approach.\nMETHODS: More than 2,000 B-ALL cases of RNA-seq data from from Eastern Cooperative Oncology Group (ECOG) and the American College of Radiology Imaging Network (ACRIN) (n=764), the Children's Oncology Group (COG), Munich Leukemia Laboratory (MLL) (n=280), and other several collaborators were analyzed to identify the new subtype. Whole genome sequence was performed to detect mutations, stractural variants, and copy number alterations. The tridimentional analysis of chromatin was performed with HiChIP.\nRESULTS: We identified the new high-risk B-ALL subtype “CDX2/UBTF” that exhibited unique gene expression profiles, which is enriched in female (77.3%), adolescents and young adults (52.6%), and relapse cohort (3.3%). CD10 negativity and IgM positivity are hallmarks of this subtype with NTRK3 expression that can be an effective marker at diagnostic approach and a potential targeted therapy with TRK and mulkinase inbitors, larotrectinib and entrectinib. Genetically, two different alterations define CDX2/UBTF. One is UBTF-ATXN7L3 fusions caused by deletion of 17q21.31, and the other is extopic CDX2 expression through the enhancer hijacking mechanism induced by deletion of 13q12.2. Other genomic features include gain of 1q and PAX5 rearrangement (PAX5-ZCCHC7), might induce upregulation of histone cluster genes and PAX5.\nCONCLUSION: We described the novel B-ALL subtype “CDX2/UBTF” that has unique clinical and genomic characteristics.","abstract":"PURPOSE: Advance in the knowledge of genomic basis of B-cell acute lymphoblastic leukemia (B-ALL) has changed the treatment approaches and diagnostic assays and improved their outcome. Despite the recent development of next generation sequencing approaches, there are still some cases that their drivers are unknown. We aimed to define and describe the characteristics of an additional B-ALL subtype by integrating genomic, transcriptomic, and epigenomic approach.\nMETHODS: More than 2,000 B-ALL cases of RNA-seq data from from Eastern Cooperative Oncology Group (ECOG) and the American College of Radiology Imaging Network (ACRIN) (n=764), the Children's Oncology Group (COG), Munich Leukemia Laboratory (MLL) (n=280), and other several collaborators were analyzed to identify the new subtype. Whole genome sequence was performed to detect mutations, stractural variants, and copy number alterations. The tridimentional analysis of chromatin was performed with HiChIP.\nRESULTS: We identified the new high-risk B-ALL subtype “CDX2/UBTF” that exhibited unique gene expression profiles, which is enriched in female (77.3%), adolescents and young adults (52.6%), and relapse cohort (3.3%). CD10 negativity and IgM positivity are hallmarks of this subtype with NTRK3 expression that can be an effective marker at diagnostic approach and a potential targeted therapy with TRK and mulkinase inbitors, larotrectinib and entrectinib. Genetically, two different alterations define CDX2/UBTF. One is UBTF-ATXN7L3 fusions caused by deletion of 17q21.31, and the other is extopic CDX2 expression through the enhancer hijacking mechanism induced by deletion of 13q12.2. Other genomic features include gain of 1q and PAX5 rearrangement (PAX5-ZCCHC7), might induce upregulation of histone cluster genes and PAX5.\nCONCLUSION: We described the novel B-ALL subtype “CDX2/UBTF” that has unique clinical and genomic characteristics.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-07T15:11:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005864","title":"Nascent transcriptome in T-ALL bone marrow","description":"Nascent RNA expression profiles were generated with Global Run-On sequencing (GRO-seq) from T-ALL patient samples to measure primary transcription genome-wide and to summarize the transcriptional activity at gene loci and enhancers.","abstract":"Nascent RNA expression profiles were generated with Global Run-On sequencing (GRO-seq) from T-ALL patient samples to measure primary transcription genome-wide and to summarize the transcriptional activity at gene loci and enhancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-07T15:33:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005865","title":"Paired healthy & tumor organoid Biobank _B15PON","description":null,"abstract":"B15PON consists  of  a panel of  organoids (three-dimensional cell cultures) of both normal, premalignant and cancer epithelial cells of  the colon. These organoids, derived from tumor as well as healthy tissue, can be propagated indefinitely and can be used to answer different research questions.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-08T15:24:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005866","title":"RNA-seq following miR-130a knock-down (KD) in Flag-tag AML1-ETO Kasumi-1 cells","description":"We performed RNA-seq on Flag-tag AML1-ETO Kasumi-1 cells transduced with Control or miR-130a KD lentiviruses to identify differentially expressed genes. Kasumi-1 cells were transduced in 3 independent replicates for control and miR-130a KD samples with lentiviruses containing GFP reporter gene. GFP+ cells were sorted 3 days post-transduction and RNA was harvested for library preparation and sequencing.","abstract":"We performed RNA-seq on Flag-tag AML1-ETO Kasumi-1 cells transduced with Control or miR-130a KD lentiviruses to identify differentially expressed genes. Kasumi-1 cells were transduced in 3 independent replicates for control and miR-130a KD samples with lentiviruses containing GFP reporter gene. GFP+ cells were sorted 3 days post-transduction and RNA was harvested for library preparation and sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-08T19:55:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005867","title":"CUT&RUN of AML1-ETO binding occupancy following miR-130a KD in Kasumi-1 cells","description":"We performed CUT&amp;RUN assay with control Ig , anti-Flag and anti-ETO antibodies in Flag-tag AML1-ETO Kasumi-1 cells to determine binding occupancy of AML1-ETO following miR-130a KD. Kasumi-1 cells were transduced in 3 independent replicates for control and miR-130a KD samples with lentiviruses containing GFP reporter gene. GFP+ cells were sorted 3 days post-transduction and the cells were used in the CUT&amp;RUN assay. Three antibodies were used for each biological sample.","abstract":"We performed CUT&amp;RUN assay with control Ig , anti-Flag and anti-ETO antibodies in Flag-tag AML1-ETO Kasumi-1 cells to determine binding occupancy of AML1-ETO following miR-130a KD. Kasumi-1 cells were transduced in 3 independent replicates for control and miR-130a KD samples with lentiviruses containing GFP reporter gene. GFP+ cells were sorted 3 days post-transduction and the cells were used in the CUT&amp;RUN assay. Three antibodies were used for each biological sample.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-08T18:55:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005868","title":"RNA-seq following miR-130a overexpression (OE) in human CD34+cord blood cells","description":"We performed RNA-seq on CD34+ human cord blood (CB) cells transduced with Control or miR-130a OE lentiviruses to identify differentially expressed genes. Sorted CD34+ cells from 3 independent cord blood pools were transduced with lentiviruses containing mOrange (mO) reporter gene. mO+ cells were sorted 3 days post-transduction and RNA was harvested for library preparation and sequencing.","abstract":"We performed RNA-seq on CD34+ human cord blood (CB) cells transduced with Control or miR-130a OE lentiviruses to identify differentially expressed genes. Sorted CD34+ cells from 3 independent cord blood pools were transduced with lentiviruses containing mOrange (mO) reporter gene. mO+ cells were sorted 3 days post-transduction and RNA was harvested for library preparation and sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-08T18:55:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005869","title":"RNA-seq following TBL1XR1 KD in human CD34+CD38- cord blood cells","description":"We performed RNA-seq on CD34+CD38- human cord blood (CB) cells transduced with sh_Control or sh_TBL1XR1 lentiviruses to identify differentially expressed genes. Sorted CD34+CD38- cells from 3 independent cord blood pools were transduced with lentiviruses containing BFP reporter gene. BFP+ cells were sorted 3 days post-transduction and RNA was harvested for library preparation and sequencing.","abstract":"We performed RNA-seq on CD34+CD38- human cord blood (CB) cells transduced with sh_Control or sh_TBL1XR1 lentiviruses to identify differentially expressed genes. Sorted CD34+CD38- cells from 3 independent cord blood pools were transduced with lentiviruses containing BFP reporter gene. BFP+ cells were sorted 3 days post-transduction and RNA was harvested for library preparation and sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-08T18:55:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005870","title":"tFL with a PMBL GE signature","description":"We investigated the clinicopathologic features of 5 follicular lymphomas (FL) that transformed to morphologic diffuse large B-cell lymphomas (DLBCL) and had a primary mediastinal large B-cell lymphoma (PMBL)-like gene expression profile. None of the transformed FL (tFL) arose in the mediastinum, all cases tested had a germinal center B-cell immunophenotype, 20% were CD30+, 60% CD23+, 80% MAL+, 20% CD200+, and 0% CD273/PDL2+. Whole exome sequencing detected alterations in genes associated with both FL/DLBCL (CREBBP, KMT2C, KMT2D, ARID1A, HIST1 members, and TNFRSF14) and PMBL (JAK-STAT pathway genes, B2M, and CD58). Copy number (CN) analysis detected gains/amplification of REL in 60% and STAT6 in 40%, gains of chromosome 16, including IL4R, in 40%, and both deletions and gains of 11q in 20%. This cohort, although limited in size, supports a subset of tFL that has blended features between FL/DLBCL and PMBL. Despite having some features that are less common in DLBCL (MAL and CD23 expression, JAK-STAT activation), these cases lack the most characteristic CN alteration seen in PMBL (9p24.1 gain/amplification). This cohort expands the biologic heterogeneity of tFL, illustrating a subset with blended FL/DLBCL and PMBL features, with potential treatment implications that include the use of novel PMBL-targeted therapies.","abstract":"We investigated the clinicopathologic features of 5 follicular lymphomas (FL) that transformed to morphologic diffuse large B-cell lymphomas (DLBCL) and had a primary mediastinal large B-cell lymphoma (PMBL)-like gene expression profile. None of the transformed FL (tFL) arose in the mediastinum, all cases tested had a germinal center B-cell immunophenotype, 20% were CD30+, 60% CD23+, 80% MAL+, 20% CD200+, and 0% CD273/PDL2+. Whole exome sequencing detected alterations in genes associated with both FL/DLBCL (CREBBP, KMT2C, KMT2D, ARID1A, HIST1 members, and TNFRSF14) and PMBL (JAK-STAT pathway genes, B2M, and CD58). Copy number (CN) analysis detected gains/amplification of REL in 60% and STAT6 in 40%, gains of chromosome 16, including IL4R, in 40%, and both deletions and gains of 11q in 20%. This cohort, although limited in size, supports a subset of tFL that has blended features between FL/DLBCL and PMBL. Despite having some features that are less common in DLBCL (MAL and CD23 expression, JAK-STAT activation), these cases lack the most characteristic CN alteration seen in PMBL (9p24.1 gain/amplification). This cohort expands the biologic heterogeneity of tFL, illustrating a subset with blended FL/DLBCL and PMBL features, with potential treatment implications that include the use of novel PMBL-targeted therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-08T20:24:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005871","title":"HCC subtypes link to distinct cell lineages and outcomes of immunotherapies","description":null,"abstract":"HCC is a highly heterogeneous disease with poor prognosis and limited treatment options. Atezolizumab (anti-PD-L1) plus bevacizumab (anti-VEGF) combination therapy has recently become the new standard of care in patients with unresectable HCC. However, not all patients derived benefit. Gaining biological insights into HCC heterogeneity is crucial for understanding the mechanisms of response and resistance to the combination immunotherapy and identifying effective new therapeutic targets. Through transcriptomic, genomic and in situ analyses in three independent HCC cohorts including an in-house advanced HCC collection (DV001918), GO30140 Phase 1b and IMbrave150 phase 3 trials, we have identified and validated three robust subtypes, i.e. cholangio-like, progenitor-like, and hepatocyte-like, based on their linkage to different liver epithelial cell lineages. These subtypes also showed distinct tumor cell-intrinsic and extrinsic features and immune landscape. Importantly, we found that the cholangio-like subtype was associated with the most benefits from the combination immunotherapy, while the progenitor-like subtype appeared to be less benefited. Using a humanized HCC xenograft mouse model that recapitulates the progenitor-like subtype, we demonstrated that GPC3/CD3 bi-specific antibody elicited a strong anti-tumor activity mediated by intratumoral recruitment and activation of T cells. Our study provides novel biological insights into HCC heterogeneity and strategies of targeting subtype-specific vulnerabilities to overcome resistance to the combination immunotherapy.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005872","title":"Defining structural variation associated with breast cancer susceptibility by long-read genome sequencing","description":"Germline structural variants (SVs) are challenging to identify by conventional genetic testing assays. Long-read sequencing has improved the global characterization of SVs, but its sensitivity at genetic loci associated with high- and moderate-penetrance cancer susceptibility has not been reported. This study used long-read genome sequencing performed on the Oxford Nanopore Technologies' PromethION to resolve variants underlying breast cancer susceptibility in sixteen individuals with pathogenic germline SVs in BRCA1, BRCA2, CHEK2 or PALB2.","abstract":"Germline structural variants (SVs) are challenging to identify by conventional genetic testing assays. Long-read sequencing has improved the global characterization of SVs, but its sensitivity at genetic loci associated with high- and moderate-penetrance cancer susceptibility has not been reported. This study used long-read genome sequencing performed on the Oxford Nanopore Technologies' PromethION to resolve variants underlying breast cancer susceptibility in sixteen individuals with pathogenic germline SVs in BRCA1, BRCA2, CHEK2 or PALB2.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-08T22:33:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005873","title":"Effects of nucleases on cell-free extrachromosomal circular DNA","description":"Effects of nucleases on cell-free extrachromosomal circular DNA","abstract":"Effects of nucleases on cell-free extrachromosomal circular DNA","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-09T07:43:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005874","title":"Identification of Germline Monoallelic Mutations in IKZF2 in Patients with Immune Dysregulation.","description":"Helios, encoded by IKZF2, is a member of the Ikaros family of transcription factors with pivotal roles in T-follicular helper, NK- and T-regulatory cell physiology. Somatic IKZF2 mutations are frequently found in lymphoid malignancies. Although germline mutations in IKZF1 and IKZF3, encoding Ikaros and Aiolos, have recently been identified in patients with phenotypically similar immunodeficiency syndromes, the effect of germline mutations in IKZF2 on human hematopoiesis and immunity remains enigmatic. We identified germline IKZF2 mutations (one nonsense (p.R291X)- and 4 distinct missense variants) in six patients with systemic lupus erythematosus, immune thrombocytopenia or EBV-associated hemophagocytic lymphohistiocytosis. Patients exhibited hypogammaglobulinemia, decreased number of T-follicular helper and NKcells. Single-cell RNA sequencing of PBMCs from the patient carrying the R291X variant revealed upregulation of pro-inflammatory genes associated with T-cell receptor activation and T-cell exhaustion. Functional assays revealed the inability of HeliosR291X to homodimerize and bind target DNA as dimers. Moreover, proteomic analysis by proximity-dependent Biotin Identification revealed aberrant interaction of 3/5 Helios mutants with core components of the NuRD complex conveying HELIOS mediated epigenetic and transcriptional dysregulation.","abstract":"Helios, encoded by IKZF2, is a member of the Ikaros family of transcription factors with pivotal roles in T-follicular helper, NK- and T-regulatory cell physiology. Somatic IKZF2 mutations are frequently found in lymphoid malignancies. Although germline mutations in IKZF1 and IKZF3, encoding Ikaros and Aiolos, have recently been identified in patients with phenotypically similar immunodeficiency syndromes, the effect of germline mutations in IKZF2 on human hematopoiesis and immunity remains enigmatic. We identified germline IKZF2 mutations (one nonsense (p.R291X)- and 4 distinct missense variants) in six patients with systemic lupus erythematosus, immune thrombocytopenia or EBV-associated hemophagocytic lymphohistiocytosis. Patients exhibited hypogammaglobulinemia, decreased number of T-follicular helper and NKcells. Single-cell RNA sequencing of PBMCs from the patient carrying the R291X variant revealed upregulation of pro-inflammatory genes associated with T-cell receptor activation and T-cell exhaustion. Functional assays revealed the inability of HeliosR291X to homodimerize and bind target DNA as dimers. Moreover, proteomic analysis by proximity-dependent Biotin Identification revealed aberrant interaction of 3/5 Helios mutants with core components of the NuRD complex conveying HELIOS mediated epigenetic and transcriptional dysregulation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-09T10:39:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005875","title":"Molecular and clinical effects of selective TYK2 inhibition with deucravacitinib in psoriasis","description":"Investigate changes in IL-23/Th17- and type I interferon-pathway biomarkers and gene responses, and measures of selectivity for TYK2 over Janus kinases (JAKs) 1–3, in patients with moderate to severe psoriasis receiving deucravacitinib.","abstract":"Investigate changes in IL-23/Th17- and type I interferon-pathway biomarkers and gene responses, and measures of selectivity for TYK2 over Janus kinases (JAKs) 1–3, in patients with moderate to severe psoriasis receiving deucravacitinib.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-13T00:41:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005876","title":"Comprehensive characterization of pre- and post-treatment samples of breast cancer reveal potential mechanisms of chemotherapy resistance","description":"When locally advanced breast cancer is treated with neoadjuvant chemotherapy, the recurrence risk is significantly higher if no complete pathologic response is achieved. Identification of the underlying resistance mechanisms is essential to select treatments with maximal efficacy and minimal toxicity. Here we employed gene expression profiles derived from 317 HER2-negative treatment-naïve breast cancer biopsies of patients who underwent neoadjuvant chemotherapy, deep whole exome and RNA-sequencing profiles of 22 matched pre- and post-treatment tumors, and treatment outcome data to identify biomarkers of response and resistance mechanisms. Molecular profiling of treatment-naïve breast cancer samples revealed that expression levels of proliferation, immune response and extracellular matrix (ECM) organization combined predict response to chemotherapy. Triple negative patients with high proliferation, high immune response and low ECM expression had a significantly better treatment response and survival benefit (HR 0.29, 95% CI 0.10-0.85; p=0.02), while in ER+ patients the opposite was seen (HR 4.73, 95% CI 1.51-14.8; 0=0.008). The characterization of paired pre-and post-treatment samples revealed that aberrations of known cancer genes were either only present in the pre-treatment sample (CDKN1B) or in the post-treatment sample(TP53, APC, CTNNB1). Proliferation-associated genes were frequently down-regulated in post-treatment ER+ tumors, but not in triple negative tumors. Genes involved in ECM were upregulated in the majority of post-chemotherapy samples. Genomic and transcriptomic differences between pre- and post-chemotherapy samples are common and may reveal potential mechanisms of therapy resistance. Our results show a wide range of distinct, but related mechanisms, with a prominent role for proliferation- and ECM-related genes.","abstract":"When locally advanced breast cancer is treated with neoadjuvant chemotherapy, the recurrence risk is significantly higher if no complete pathologic response is achieved. Identification of the underlying resistance mechanisms is essential to select treatments with maximal efficacy and minimal toxicity. Here we employed gene expression profiles derived from 317 HER2-negative treatment-naïve breast cancer biopsies of patients who underwent neoadjuvant chemotherapy, deep whole exome and RNA-sequencing profiles of 22 matched pre- and post-treatment tumors, and treatment outcome data to identify biomarkers of response and resistance mechanisms. Molecular profiling of treatment-naïve breast cancer samples revealed that expression levels of proliferation, immune response and extracellular matrix (ECM) organization combined predict response to chemotherapy. Triple negative patients with high proliferation, high immune response and low ECM expression had a significantly better treatment response and survival benefit (HR 0.29, 95% CI 0.10-0.85; p=0.02), while in ER+ patients the opposite was seen (HR 4.73, 95% CI 1.51-14.8; 0=0.008). The characterization of paired pre-and post-treatment samples revealed that aberrations of known cancer genes were either only present in the pre-treatment sample (CDKN1B) or in the post-treatment sample(TP53, APC, CTNNB1). Proliferation-associated genes were frequently down-regulated in post-treatment ER+ tumors, but not in triple negative tumors. Genes involved in ECM were upregulated in the majority of post-chemotherapy samples. Genomic and transcriptomic differences between pre- and post-chemotherapy samples are common and may reveal potential mechanisms of therapy resistance. Our results show a wide range of distinct, but related mechanisms, with a prominent role for proliferation- and ECM-related genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-13T10:16:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005877","title":"Synthetic_Genomics","description":"have transferred several EGFP-Neo-labelled human chromosomes from RPE1 cells to mouse embryonic stem cells (mESC), a putative genome assembly ortogonal cellular platform. DNA sequencing of the resulting monochromosomal-hybrid cells is required to characterise in depth the quality of chromosome transfer comparing its sequence before and after delivery to the receiving mESC. Similar sequencing analysis is required to characterise the integrity and copy number of the opposite chromosome transfer from mESC to human cells (hIPSC and RPE1).","abstract":"This study aims at validating and optimising new methods for chromosome transfer and human genome assembly.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005878","title":"A recessive PRDM13 mutation results in congenital hypogonadotropic hypogonadism and cerebellar hypoplasia","description":"The PRDM13 (PR Domain containing 13) putative chromatin modifier and transcriptional regulator functions downstream of the transcription factor PTF1A, which controls GABAergic fate in the spinal cord and neurogenesis in the hypothalamus. Here, we report a novel, recessive syndrome associated with PRDM13 mutation. Patients exhibited intellectual disability, ataxia with cerebellar hypoplasia, scoliosis and delayed puberty with congenital hypogonadotropic hypogonadism (CHH). Expression studies revealed Prdm13/PRDM13 transcripts in the developing hypothalamus and cerebellum in mouse and human. An analysis of hypothalamus and cerebellum development in mice homozygous for a Prdm13 mutant allele revealed a significant reduction in the number of Kisspeptin (Kiss1) neurons in the hypothalamus and PAX2+ progenitors emerging from the cerebellar ventricular zone. The latter was accompanied by ectopic expression of the glutamatergic lineage marker TLX3. Prdm13-deficient mice displayed cerebellar hypoplasia, normal gonadal structure, but delayed pubertal onset. Together, these findings identify PRDM13 as a critical regulator of GABAergic cell fate in the cerebellum and of hypothalamic kisspeptin neuron development, providing a mechanistic explanation for the co-occurrence of CHH and cerebellar hypoplasia in this syndrome. To our knowledge, this is the first evidence linking disrupted PRDM13-mediated regulation of Kiss1 neurons to CHH in humans.","abstract":"The PRDM13 (PR Domain containing 13) putative chromatin modifier and transcriptional regulator functions downstream of the transcription factor PTF1A, which controls GABAergic fate in the spinal cord and neurogenesis in the hypothalamus. Here, we report a novel, recessive syndrome associated with PRDM13 mutation. Patients exhibited intellectual disability, ataxia with cerebellar hypoplasia, scoliosis and delayed puberty with congenital hypogonadotropic hypogonadism (CHH). Expression studies revealed Prdm13/PRDM13 transcripts in the developing hypothalamus and cerebellum in mouse and human. An analysis of hypothalamus and cerebellum development in mice homozygous for a Prdm13 mutant allele revealed a significant reduction in the number of Kisspeptin (Kiss1) neurons in the hypothalamus and PAX2+ progenitors emerging from the cerebellar ventricular zone. The latter was accompanied by ectopic expression of the glutamatergic lineage marker TLX3. Prdm13-deficient mice displayed cerebellar hypoplasia, normal gonadal structure, but delayed pubertal onset. Together, these findings identify PRDM13 as a critical regulator of GABAergic cell fate in the cerebellum and of hypothalamic kisspeptin neuron development, providing a mechanistic explanation for the co-occurrence of CHH and cerebellar hypoplasia in this syndrome. To our knowledge, this is the first evidence linking disrupted PRDM13-mediated regulation of Kiss1 neurons to CHH in humans.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-13T13:11:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005879","title":"Deciphering RBP - alternative splicing networks in ALS iPSC-MN: patient and control datasets","description":"We produce RNA-seq datasets of iPSC-derived motor neurons (iPSC-MN) from healthy controls and sporadic ALS patients and controls and familial ALS patients with pathogenic variants in TARDBP.","abstract":"We produce RNA-seq datasets of iPSC-derived motor neurons (iPSC-MN) from healthy controls and sporadic ALS patients and controls and familial ALS patients with pathogenic variants in TARDBP.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-13T18:19:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005880","title":"Deciphering RBP - alternative splicing networks in ALS iPSC-MN: TDP-43, NOVA1, NOVA2 and RBFOX2 eCLIP-seq","description":"We produced enhanced cross-linking immunoprecipitation (eCLIP) sequencing data of the RNA binding proteins (RBP) TDP-43, NOVA1, NOVA2 and RBFOX2 in iPSC motor neurons of two healthy control individuals, respectively.","abstract":"We produced enhanced cross-linking immunoprecipitation (eCLIP) sequencing data of the RNA binding proteins (RBP) TDP-43, NOVA1, NOVA2 and RBFOX2 in iPSC motor neurons of two healthy control individuals, respectively.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-13T18:19:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005881","title":"Deciphering RBP - alternative splicing networks in ALS iPSC-MN: NOVA1 gain and loss of function systems","description":"We produced NOVA1 and EGFP over-expression RNA-seq datasets in three healthy control individuals using lentivirus-mediated gene transfer to model NOVA1 gain of function. Additionally, we produced a NOVA1 loss of function RNA-seq dataset by generating iPSC-MN with NOVA1 knock out produced by CRISPR/Cas9 in the CV-B iPSC line.","abstract":"We produced NOVA1 and EGFP over-expression RNA-seq datasets in three healthy control individuals using lentivirus-mediated gene transfer to model NOVA1 gain of function. Additionally, we produced a NOVA1 loss of function RNA-seq dataset by generating iPSC-MN with NOVA1 knock out produced by CRISPR/Cas9 in the CV-B iPSC line.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-13T18:19:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005882","title":"DERMATLAS_Mixed_tumour_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are cutaneous mixed tumors.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are cutaneous mixed tumors.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005883","title":"DERMATLAS_Mixed_tumour_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are cutaneous mixed tumors.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are cutaneous mixed tumors.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005884","title":"DERMATLAS_Myoepithelioma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are myoepitheliomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are myoepitheliomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005885","title":"DERMATLAS_Myoepithelioma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are myoepitheliomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are myoepitheliomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005886","title":"3D-GSC_expression_profiles","description":null,"abstract":"In this study, we used RNA-sequencing gene expression profiling in order to characterize specific phenotypic traits in DIPG-derived glioma stem cell (GSC) models. Twenty-two primary GSC models derived from biopsies collected at diagnosis were cultured in an ECM-mimicking compound before for RNA extraction and subsequent rRNA-depletion and sequencing .","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005887","title":"Patient-derived tumor organoids for personalized medicine in a rare case of hepatocellular carcinoma with neuroendocrine differentiation.","description":"We report the case of a 74-year-old man with a very rare subtype of hepatocellular carcinoma with neuroendocrine differentiation (HCC-NED). The patient presented with two independent tumors, a gastrointestinal stromal tumor in the stomach and a hepatocellular carcinoma in the liver. Both tumors were surgically removed in curative intent. Histopathological work-up of the liver tumor revealed poorly differentiated hepatocellular carcinoma (Edmondson-Steiner grade IV) with diffuse expression of neuroendocrine markers synaptophysin (SYP) and chromogranin (CHGA). Three months after resection, multifocal recurrence of the HCC with neuroendocrine differentiation (HCC-NED) was observed. In the meantime, tumor organoids have been generated from the resected HCC-NED and extensively characterized. Sensitivity to a number of drugs approved for the treatment of HCC or neuroendocrine carcinomas was tested in vitro. Based on their in vitro efficacy, etoposide and carboplatin were used as first line palliative combination treatment.  Because genomic analysis revealed a NTRK1-mutation (kinase domain) and tumor organoids were sensitive to entrectinib, a pan-TRK inhibitor, the patient received entrectinib as second line therapy. After only two weeks, treatment had to be discontinued due to deterioration of the patient’s general condition. In conclusion, we demonstrate for the first time that preclinical drug testing using organoids is feasible in selected HCC cases.","abstract":"We report the case of a 74-year-old man with a very rare subtype of hepatocellular carcinoma with neuroendocrine differentiation (HCC-NED). The patient presented with two independent tumors, a gastrointestinal stromal tumor in the stomach and a hepatocellular carcinoma in the liver. Both tumors were surgically removed in curative intent. Histopathological work-up of the liver tumor revealed poorly differentiated hepatocellular carcinoma (Edmondson-Steiner grade IV) with diffuse expression of neuroendocrine markers synaptophysin (SYP) and chromogranin (CHGA). Three months after resection, multifocal recurrence of the HCC with neuroendocrine differentiation (HCC-NED) was observed. In the meantime, tumor organoids have been generated from the resected HCC-NED and extensively characterized. Sensitivity to a number of drugs approved for the treatment of HCC or neuroendocrine carcinomas was tested in vitro. Based on their in vitro efficacy, etoposide and carboplatin were used as first line palliative combination treatment.  Because genomic analysis revealed a NTRK1-mutation (kinase domain) and tumor organoids were sensitive to entrectinib, a pan-TRK inhibitor, the patient received entrectinib as second line therapy. After only two weeks, treatment had to be discontinued due to deterioration of the patient’s general condition. In conclusion, we demonstrate for the first time that preclinical drug testing using organoids is feasible in selected HCC cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-14T18:39:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005888","title":"300TZFG","description":"Identification of genetic variants associated with induced cytokine production.","abstract":"Identification of genetic variants associated with induced cytokine production.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005889","title":"Single cell analysis of cultivated fibroblasts from chronic pancreatitis and pancreatic cancer patients","description":null,"abstract":"Cancer-associated fibroblasts, which are derived from several cell types such as pancreatic stellate cells or mesenchymal stem cells, play a major role in the progression and drug resistance of pancreatic cancer. Targeting cancer-associated fibroblasts can be a promising therapeutic strategy. Recent studies suggest that cancer-associated fibroblasts exhibit functional heterogeneity with distinct gene expression profiling in pancreatic cancer, such as myofibroblastic, inflammatory, and antigen-presenting cancer-associated fibroblasts. However, intra-tumoral heterogeneity of cancer-associated fibroblasts in pancreatic cancer patients and their pivotal role in cancer-related mechanism has not been fully elucidated. In this study, we used cancer-associated fibroblasts primary isolated from pancreatic cancer patients and chronic pancreatitis patient via outgrowth method to see whether we can detect myofibroblastic, inflammatory, and antigen-presenting cancer-associated fibroblast clusters in patient specimens, and whether we can identify novel cancer-associated fibroblast subtypes potentially associated with pancreatic diseases development or progression.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005890","title":"Detection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis using aneuploidy and mutation identification in plasma","description":"Malignant peripheral nerve sheath tumors (MPNST) are the deadliest cancer that arises in individuals diagnosed with neurofibromatosis and account for nearly 5% of the 15,000 soft tissue sarcomas diagnosed in the United States each year. Comprised of neoplastic Schwann cells, primary risk factors for developing MPNST include existing plexiform neurofibromas (PN), prior radiotherapy treatment, and expansive germline mutations involving the entire NF1 gene and surrounding genes. PN develop in nearly 30-50% of patients with NF1 and most often grow rapidly in the first decade of life. One of the most important aspects of clinical care for NF1 patients is monitoring PN for signs of malignant transformation to MPNST that occurs in 10-15% of patients. We perform aneuploidy analysis on ctDNA from 883 ostensibly healthy individuals and 28 patients with neurofibromas, including 7 patients with benign neurofibroma, 9 patients with PN and 12 patients with MPNST. Overall sensitivity for detecting MPNST using genome wide aneuploidy scoring was 33%, and analysis of sub-chromosomal copy number alterations (CNAs) improved sensitivity to 50% while retaining a high specificity of 97%. In addition, we performed mutation analysis on plasma cfDNA for a subset of patients and identified mutations in NF1, NF2, RB1, TP53BP2, and GOLGA2. Given the high throughput and relatively low sequencing coverage required by our assay, liquid biopsy represents a promising technology to identify incipient MPNST.","abstract":"Malignant peripheral nerve sheath tumors (MPNST) are the deadliest cancer that arises in individuals diagnosed with neurofibromatosis and account for nearly 5% of the 15,000 soft tissue sarcomas diagnosed in the United States each year. Comprised of neoplastic Schwann cells, primary risk factors for developing MPNST include existing plexiform neurofibromas (PN), prior radiotherapy treatment, and expansive germline mutations involving the entire NF1 gene and surrounding genes. PN develop in nearly 30-50% of patients with NF1 and most often grow rapidly in the first decade of life. One of the most important aspects of clinical care for NF1 patients is monitoring PN for signs of malignant transformation to MPNST that occurs in 10-15% of patients. We perform aneuploidy analysis on ctDNA from 883 ostensibly healthy individuals and 28 patients with neurofibromas, including 7 patients with benign neurofibroma, 9 patients with PN and 12 patients with MPNST. Overall sensitivity for detecting MPNST using genome wide aneuploidy scoring was 33%, and analysis of sub-chromosomal copy number alterations (CNAs) improved sensitivity to 50% while retaining a high specificity of 97%. In addition, we performed mutation analysis on plasma cfDNA for a subset of patients and identified mutations in NF1, NF2, RB1, TP53BP2, and GOLGA2. Given the high throughput and relatively low sequencing coverage required by our assay, liquid biopsy represents a promising technology to identify incipient MPNST.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005891","title":"Comparison of fresh and slow-frozen cancer samples for different applications","description":"Surplus tissues from multiple solid human cancers directly slow-frozen after resection can subsequently be used for different types of methods including the establishment of 2D, 3D, and ex vivo cultures as well as single cell RNA sequencing (scRNAseq) with similar results when compared to freshly analyzed material.","abstract":"Surplus tissues from multiple solid human cancers directly slow-frozen after resection can subsequently be used for different types of methods including the establishment of 2D, 3D, and ex vivo cultures as well as single cell RNA sequencing (scRNAseq) with similar results when compared to freshly analyzed material.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-16T16:59:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005892","title":"Functional Mapping of AKT Signaling and Biomarkers of Response From the FAIRLANE Trial of Neoadjuvant Ipatasertib Plus Paclitaxel for Triple-Negative Breast Cancer","description":"Purpose: Despite extensive genomic and transcriptomic profiling, it remains unknown how signaling pathways are differentially activated and how tumors are differentially sensitized to certain perturbations. Here, we aim to characterize AKT signaling activity and its association with other genomic or immunohistochemistry-based PI3K/AKT pathway biomarkers as well as the clinical activity of ipatasertib (AKT inhibitor) in the FAIRLANE trial. Experimental Design: In FAIRLANE, 151 patients with early triple-negative breast cancer were randomized 1:1 to receive paclitaxel with ipatasertib or placebo for 12 weeks prior to surgery. Adding ipatasertib did not increase pathologic complete response rate and numerically improved overall response rate by magnetic resonance imaging (MRI). We used reverse-phase protein microarrays (RPPA) to examine the total level and/or phosphorylation states of over 100 proteins in various signaling or cell processes including PI3K/AKT and mTOR signaling. 125 baseline and 127 on-treatment samples were evaluable by RPPA, with 110 paired samples at both time points. Results: Tumors with genomic/protein alterations in PIK3CA/AKT1/PTEN were associated with higher levels of AKT phosphorylation. In addition, phosphorylated(p)AKT levels exhibited a significant association with enriched clinical benefit of ipatasertib, and identified patients who received benefit in the absence of PIK3CA/AKT1/PTEN alterations. Ipatasertib treatment led to a down-regulation of AKT/mTORC1 signaling, which was more pronounced among the tumors with PIK3CA/AKT1/PTEN alterations or among the responders to the treatment. Conclusions: We showed that the high baseline pAKT levels are associated with the alterations of PI3K/AKT pathway components and enriched benefit of ipatasertib in TNBC.","abstract":"Purpose: Despite extensive genomic and transcriptomic profiling, it remains unknown how signaling pathways are differentially activated and how tumors are differentially sensitized to certain perturbations. Here, we aim to characterize AKT signaling activity and its association with other genomic or immunohistochemistry-based PI3K/AKT pathway biomarkers as well as the clinical activity of ipatasertib (AKT inhibitor) in the FAIRLANE trial. Experimental Design: In FAIRLANE, 151 patients with early triple-negative breast cancer were randomized 1:1 to receive paclitaxel with ipatasertib or placebo for 12 weeks prior to surgery. Adding ipatasertib did not increase pathologic complete response rate and numerically improved overall response rate by magnetic resonance imaging (MRI). We used reverse-phase protein microarrays (RPPA) to examine the total level and/or phosphorylation states of over 100 proteins in various signaling or cell processes including PI3K/AKT and mTOR signaling. 125 baseline and 127 on-treatment samples were evaluable by RPPA, with 110 paired samples at both time points. Results: Tumors with genomic/protein alterations in PIK3CA/AKT1/PTEN were associated with higher levels of AKT phosphorylation. In addition, phosphorylated(p)AKT levels exhibited a significant association with enriched clinical benefit of ipatasertib, and identified patients who received benefit in the absence of PIK3CA/AKT1/PTEN alterations. Ipatasertib treatment led to a down-regulation of AKT/mTORC1 signaling, which was more pronounced among the tumors with PIK3CA/AKT1/PTEN alterations or among the responders to the treatment. Conclusions: We showed that the high baseline pAKT levels are associated with the alterations of PI3K/AKT pathway components and enriched benefit of ipatasertib in TNBC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-17T01:35:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005893","title":"Initial cohort of 500 solid tumors screened for Basket of Baskets","description":null,"abstract":"NGS cancer gene panel seq profiled across 500 solid tumors screened for the Basket of Baskets study","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-17T09:48:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005894","title":"Blood-based monitoring of relapsed/refractory cHL patients predict responses to PD-1 blockade treatment","description":"Hodgkin lymphoma (cHL) patients are uniquely susceptible to treatment with programmed cell death-1 (PD-1) treatment. However, monitoring with FDG-PET/CT, the current response detection standard, is challenging. Here, we address the potential applicability of tissue biomarkers and blood-based biomarkers in PD-1 treated cHL patients. We evaluated 9p24.1/PD-L1/PD-L2 alterations, and expression of PD-L1 and antigen presentation molecules (HLA class I/II) in 9 tissue biopsies of 4 patients. In addition, we assessed circulating tumor DNA (ctDNA), extracellular vesicle associated miRNAs (EV-miRNAs), soluble PD-L1 and serum TARC (sTARC) in 26 longitudinal blood samples of these patients during PD-1 treatment. We found that the predictive power of tissue biomarkers is dependent on the timing of the biopsy . The dynamics of blood-based biomarkers: sTARC, EV-miRNAs and ctDNA corresponded well  immunotherapy treatment response. Therefore, blood-based biomarkers are promising monitoring strategies in PD-1 treated cHL patients and should be further explored in clinical trials or observational studies.","abstract":"Hodgkin lymphoma (cHL) patients are uniquely susceptible to treatment with programmed cell death-1 (PD-1) treatment. However, monitoring with FDG-PET/CT, the current response detection standard, is challenging. Here, we address the potential applicability of tissue biomarkers and blood-based biomarkers in PD-1 treated cHL patients. We evaluated 9p24.1/PD-L1/PD-L2 alterations, and expression of PD-L1 and antigen presentation molecules (HLA class I/II) in 9 tissue biopsies of 4 patients. In addition, we assessed circulating tumor DNA (ctDNA), extracellular vesicle associated miRNAs (EV-miRNAs), soluble PD-L1 and serum TARC (sTARC) in 26 longitudinal blood samples of these patients during PD-1 treatment. We found that the predictive power of tissue biomarkers is dependent on the timing of the biopsy . The dynamics of blood-based biomarkers: sTARC, EV-miRNAs and ctDNA corresponded well  immunotherapy treatment response. Therefore, blood-based biomarkers are promising monitoring strategies in PD-1 treated cHL patients and should be further explored in clinical trials or observational studies.","study_type":"Cancer Genomics","pubmed_ids":[35813096],"external_links":null,"is_released":true,"released_date":"2024-12-31T13:50:26.745381+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005895","title":"INSIGHT: VHL Case Report","description":"The overall goal of this study is to uncover contributors to inherited cancer through analysis of individuals and families with, or at risk of, a hereditary cancer syndrome. In addition, we hope to elucidate novel mechanisms of tumourigenesis in hereditary cancer patients. This specific report highlights a rare case of VHL mosaicism and shows the value of tissue testing in VHL variant negative cases.","abstract":"The overall goal of this study is to uncover contributors to inherited cancer through analysis of individuals and families with, or at risk of, a hereditary cancer syndrome. In addition, we hope to elucidate novel mechanisms of tumourigenesis in hereditary cancer patients. This specific report highlights a rare case of VHL mosaicism and shows the value of tissue testing in VHL variant negative cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-17T15:15:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005896","title":"KLK5 induced gene expression in A549 cells","description":null,"abstract":"Clinical studies of type 2 (T2) cytokine-related neutralizing antibodies in asthma have identified a substantial subset of patients with low levels of T2 inflammation who do not benefit from T2 cytokine neutralizing antibody treatment.  Non type 2 mechanisms are poorly understood in asthma but represent the redefined unmet medical need. We utilized an unbiased genome-wide association study (GWAS) of moderate-severe asthma patients stratified by high or low T2 serum biomarkers. We also performed additional expression and biological analysis for the top genetic hit. This analysis identified a novel protective SNP at chr19q13.41 which is selectively associated with T2-low asthma and establishes KLK5 as the causal gene mediating this association.  Heterozygous carriers of the SNP have reduced KLK5 expression.  KLK5 is secreted by human bronchial epithelial cells and elevated in asthma bronchial alveolar lavage.  T2 cytokines IL-4 and IL-13 downregulate KLK5 in human bronchial epithelial cells.  KLK5, dependent on its catalytic function, induces epithelial chemokine/cytokine expression.  Lastly, overexpression of KLK5 in airway, or lack of an endogenous KLK5 inhibitor, SPINK5, leads to spontaneous airway neutrophilic inflammation.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005897","title":"Origins and timing of emerging lesions in advanced renal cell carcinoma","description":"Renal cell carcinoma (RCC) with venous tumor thrombus (VTT) arising from the primary tumor occurs in ~10% of cases and is thought to represent more advanced disease.  RCC with VTT and distant metastasis provides unique opportunities to examine the origins and relative timing of tumor lesion emergence and to identify molecular correlates with disease state.  We performed multi-region exome and RNA sequencing analysis of a clinical cohort of 16 RCC patients with VTT, with eight patients also having sequenced metastasis, to examine which genomic alterations, biological pathways, and evolutionary processes contribute to VTT and metastasis, and to ask whether metastasis typically arises directly from VTT or is independent of VTT.","abstract":"Renal cell carcinoma (RCC) with venous tumor thrombus (VTT) arising from the primary tumor occurs in ~10% of cases and is thought to represent more advanced disease.  RCC with VTT and distant metastasis provides unique opportunities to examine the origins and relative timing of tumor lesion emergence and to identify molecular correlates with disease state.  We performed multi-region exome and RNA sequencing analysis of a clinical cohort of 16 RCC patients with VTT, with eight patients also having sequenced metastasis, to examine which genomic alterations, biological pathways, and evolutionary processes contribute to VTT and metastasis, and to ask whether metastasis typically arises directly from VTT or is independent of VTT.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-19T07:18:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005898","title":"TGS1 mediates 2,2,7-trimethyl guanosine capping of the human telomerase RNA in lung tumor organoids","description":null,"abstract":"Pathways that direct the selection of the telomerase-dependent or recombination-based, alternative lengthening of telomere pathway (ALT) in cancer cells are poorly understood. Using human lung tumor organoids and classic lung cancer cells we show that formation of the 2,2,7- trimethylguanosine (TMG) cap structure at the human telomerase RNA 5’ end by the Trimethylguanosine Synthase 1 (TGS1) is central for recruiting telomerase to telomeres and engaging Cajal bodies in telomere maintenance. Treatment of tumor organoids and lung cancer cell lines with the TGS1 inhibitor sinefungin leads to Exonuclease 1 mediated generation of telomere 3’ end protrusions that engage in RAD51-dependent, homology directed recombination and the activation of key features of the ALT pathway. This indicates a critical role for 2,2,7-TMG capping of the RNA component of human telomerase (hTR) in enforcing telomerase-dependent telomere maintenance to restrict the formation of telomeric substrates conductive to ALT. Lung tumor organoids shown in this study were obtained from three patients diagnosed with lung cancer. Criteria for patient enrolment to the observational study: Age: ≥ 18; size of lesion: ≥1cm; absence of documented infectious disease, absence of metastases; absence of neoadjuvant therapy; informed patient consent was obtained from all enrolled individuals. Tumor organoids recapitulate the tissue architecture of the primary lung tumors and maintain key aspects of genomic alterations of the original tumors after expansion in tissue culture. For each patient DNA was obtained from matched lung tumor tissue, normal lung tissue and lung tumor organoid cultures and whole exome sequencing (WES) was performed.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005899","title":"Targeted de novo phasing and long-range assembly by template mutagenesis","description":null,"abstract":"Long-range sequencing with low error rate has been challenging. Sequence assembly and phasing usually require a high-quality reference genome for mapping, so working on highly-variable genomic regions or regions with no reference genome information would be difficult. In this study, we describe novel bench protocols and algorithms to obtain ultra-low-error-rate haplotype-phased sequence assemblies of regions 10 KB in length using a short-read sequencing platform that simultaneously solves the above two problems. We accomplish this by imprinting each template strand from a target region with a dense and unique mutation pattern. The mutation process randomly and independently converts ~50% of cytosines to uracils. Short-read sequencing libraries are made from both mutated and unmutated templates. A conservative de Bruijn graph approach seeds an assembly of the mutated templates, which we then extend by mapping paired-end reads. We next partition the template assemblies into two or more haplotypes after using the unmutated sequence library to recover almost all of the mutated bases. The final haplotype is assembled and corrected for residual template mutations and PCR errors. We obtain per-base-error rates below 10 9. We apply this method to a human family, correctly assembling and phasing three genomic intervals, including the highly polymorphic HLA-B gene.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-20T15:25:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005900","title":"Gut metagenome associations with extensive digital health data in a volunteer-based EstMB cohort","description":"Microbiome research is starting to move beyond the exploratory phase towards interventional trials and therefore well-characterized cohorts will be instrumental for generating hypothesis and providing new knowledge. As part of the Estonian Biobank, we established the Estonian Microbiome Cohort  which includes stool, oral and plasma samples from 2,509 participants and is supplemented with multi-omic measurements, questionnaires, and regular linkages to national electronic health records. In this study, we analyzed stool data from deep metagenomic sequencing together with rich phenotyping, including 71 diseases, 136 medications, 21 dietary questions, 5 procedures, and 19 other factors. The data revealed numerous relationships with different microbiome features. Additionally, the long-term antibiotic usage, independent from recent administration, has a significant impact on the microbiome composition, partly explaining the common associations between diseases. Overall, this study extends the understanding of microbiome–host interactions and facilitates the development of microbiome-related studies.","abstract":"Microbiome research is starting to move beyond the exploratory phase towards interventional trials and therefore well-characterized cohorts will be instrumental for generating hypothesis and providing new knowledge. As part of the Estonian Biobank, we established the Estonian Microbiome Cohort  which includes stool, oral and plasma samples from 2,509 participants and is supplemented with multi-omic measurements, questionnaires, and regular linkages to national electronic health records. In this study, we analyzed stool data from deep metagenomic sequencing together with rich phenotyping, including 71 diseases, 136 medications, 21 dietary questions, 5 procedures, and 19 other factors. The data revealed numerous relationships with different microbiome features. Additionally, the long-term antibiotic usage, independent from recent administration, has a significant impact on the microbiome composition, partly explaining the common associations between diseases. Overall, this study extends the understanding of microbiome–host interactions and facilitates the development of microbiome-related studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-21T11:15:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005901","title":"Integrative single-cell tracking of genome evolution and tumor cell plasticity in Small Cell Lung Cancer (SCLC)","description":null,"abstract":"SCLC is the deadliest type of lung cancer, which is mostly diagnosed at late stages and accounts for 15% of pulmonary tumors. Even though chemotherapy is initially effective, SCLC patients relapse quickly with therapy resistant tumors. Genome studies revealed universal loss of TP53 and RB1; recent transcriptional studies categorized SCLC tumors based on the expression of 4 lineage transcription factors (TFs). We aimed to dissect how genomic cues impact transcriptional phenotypes, tumor cell plasticity and the dynamics of tumor and immune cell interactions, to thus decipher molecular mechanisms of phenotypic divergence and therapy resistance in SCLC.\n\nWe performed genome sequencing and single cell transcriptome profiling on more than 60 SCLC patient tumors. Single cell RNA-seq was performed with the 10x Genomics platform for patient tumors to study cancer cells and the tumor micro-environment, and on xenograft models to study tumor cell intrinsic heterogeneity. Single cell and genome sequencing data were processed with an in-house pipeline. To further validate our findings on the transcriptional level, we performed imaging mass cytometry (IMC) of matched tissue samples to delineate the spatial context of cellular subsets.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005902","title":"Whole genome and exome sequencing data of  invasive micropapillary carcinoma of breast","description":"This study contains whole genome sequencing data, whole exon sequencing data and mutation files of IMPC tumor and normal tissue sample.","abstract":"This study contains whole genome sequencing data, whole exon sequencing data and mutation files of IMPC tumor and normal tissue sample.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-22T18:12:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005903","title":"Functional screening on patient-derived organoids identifies a therapeutic bispecific antibody that triggers EGFR degradation in LGR5+ tumor cells","description":null,"abstract":"Patient-derived organoids (PDOs) have demonstrated predictive value in prospective clinical trials supporting selection of personalized treatments. Because PDOs retain the organization and physiological functions of their source tissue, PDO biobanks could also be an ideal substrate to screen for novel therapeutic interventions. \nHere we describe a large-scale functional screen of dual targeting bispecific antibodies (bAbs) on a colorectal cancer (CRC) PDO biobank to target their dependency on cancer stem cells.\nA novel drug discovery pipeline was assembled where therapeutic bAb panels generated against WNT and receptor tyrosine kinases (RTK) targets were functionally evaluated by high content imaging to capture the complexity of PDO responses across a wide range of different CRCs and paired normal colonic mucosa samples. Our strategy resulted in a bAb that specifically triggers EGFR degradation in LGR5+ CSCs and that exhibits unique therapeutic properties such as potent growth inhibition of KRAS mutant CRCs, blockade of metastasis initiation in preclinical models and minimal toxicity towards normal LGR5+ colon stem cells.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005904","title":"A transcriptome atlas of human skeletal muscles","description":"We generated a large transcriptome atlas of human skeletal muscles by collecting biopsies from 6 different muscles to determine molecular signatures that may be distinct between leg muscles. The biopsies were collected from gracilis (GR),  semitendinosus (ST),  vastus lateralis (VL), vastus medialis (VM), rectus femoris (RF), and gastrocnemius lateralis (GL) muscles. We also investigated molecular differences within the muscle by including two biopsies from the middle and distal sides of the semitendinosus muscle (STM and STD, respectively). In total, 128 samples from 20 individuals (aged 25 ± 3.6 yr) were analyzed.","abstract":"We generated a large transcriptome atlas of human skeletal muscles by collecting biopsies from 6 different muscles to determine molecular signatures that may be distinct between leg muscles. The biopsies were collected from gracilis (GR),  semitendinosus (ST),  vastus lateralis (VL), vastus medialis (VM), rectus femoris (RF), and gastrocnemius lateralis (GL) muscles. We also investigated molecular differences within the muscle by including two biopsies from the middle and distal sides of the semitendinosus muscle (STM and STD, respectively). In total, 128 samples from 20 individuals (aged 25 ± 3.6 yr) were analyzed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-23T13:18:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005905","title":"Reproducibility of 10x Genomics single cell RNA sequencing method in the immune cell environment","description":null,"abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-27T22:38:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005906","title":"Exome-wide mutation analysis of cell-free DNA to simultaneously monitor the full spectrum of cancer treatment outcomes","description":"Purpose: Cell-free DNA (cfDNA) offers a non-invasive approach to monitor cancer. Here we develop a method using whole-exome sequencing (WES) of cfDNA for simultaneously monitoring the full spectrum of cancer treatment outcomes, including MRD, recurrence, evolution, and second primary cancers. Experimental Design: Three simulation datasets were generated from 26 cancer patients to benchmark the detection performance of MRD/recurrence and second primary cancers. For further validation, cfDNA samples (n=76) from cancer patients (n=35) with six different cancer types were used for performance validation during various treatments.Results: We present a cfDNA-based cancer monitoring method, named cfTrack. Taking advantage of the broad genome coverage of WES data, cfTrack can sensitively detect MRD and cancer recurrence by integrating signals across known clonal tumor mutations of a patient. In addition, cfTrack detects tumor evolution and second primary cancers by de novo identifying emerging tumor mutations. A series of machine learning and statistical denoising techniques are applied to enhance the detection power. On the simulation data, cfTrack achieved an average AUC of 99% on the validation dataset and 100% on the independent dataset in detecting recurrence in samples with tumor fraction ≥0.05%. In addition, cfTrack yielded an average AUC of 88% in detecting second primary cancers in samples with tumor fraction ≥0.2%. On real data, cfTrack accurately monitors tumor evolution during treatment, which cannot be accomplished by previous methods.Conclusion: Our results demonstrated that cfTrack can sensitively and specifically monitor the full spectrum of cancer treatment outcomes using exome-wide mutation analysis of cfDNA.","abstract":"Purpose: Cell-free DNA (cfDNA) offers a non-invasive approach to monitor cancer. Here we develop a method using whole-exome sequencing (WES) of cfDNA for simultaneously monitoring the full spectrum of cancer treatment outcomes, including MRD, recurrence, evolution, and second primary cancers. Experimental Design: Three simulation datasets were generated from 26 cancer patients to benchmark the detection performance of MRD/recurrence and second primary cancers. For further validation, cfDNA samples (n=76) from cancer patients (n=35) with six different cancer types were used for performance validation during various treatments.Results: We present a cfDNA-based cancer monitoring method, named cfTrack. Taking advantage of the broad genome coverage of WES data, cfTrack can sensitively detect MRD and cancer recurrence by integrating signals across known clonal tumor mutations of a patient. In addition, cfTrack detects tumor evolution and second primary cancers by de novo identifying emerging tumor mutations. A series of machine learning and statistical denoising techniques are applied to enhance the detection power. On the simulation data, cfTrack achieved an average AUC of 99% on the validation dataset and 100% on the independent dataset in detecting recurrence in samples with tumor fraction ≥0.05%. In addition, cfTrack yielded an average AUC of 88% in detecting second primary cancers in samples with tumor fraction ≥0.2%. On real data, cfTrack accurately monitors tumor evolution during treatment, which cannot be accomplished by previous methods.Conclusion: Our results demonstrated that cfTrack can sensitively and specifically monitor the full spectrum of cancer treatment outcomes using exome-wide mutation analysis of cfDNA.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-30T06:09:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005907","title":"iPSC-derived Human Neurofibromas","description":null,"abstract":"Plexiform neurofibromas (pNFs) are tumors that appear during development in Neurofibromatosis type 1 individuals, constituting a major morbidity source. Some will undergo malignant transformation to a highly metastatic soft tissue sarcoma termed MPNST. pNFs arise after inactivation of NF1 in a cell of the neural crest (NC)-Schwann cell (SC) lineage. To gain insight in its characterization, we used NF1(-/-) iPSCs to differentiate them into NCs and further to SCs. We generated 2D cultures and a 3D system consisting of homotypic (SCs) or heterotypic (SCs and pNF-derived endoneurial fibroblasts) spheroids. Using NF1(+/+) iPSCs, we constructed an in vitro NC-SC lineage expression roadmap to monitor differentiating NF1(-/-) SC systems. As predicted by expression, mouse sciatic nerve engraftment of 2D cultures, acquired a NC-mesenchymal fate, while heterotypic spheroids consistently formed human neurofibroma-like tumors. Endoneurial fibroblasts helped maintaining highly proliferative NF1(-/-) cells committed towards the NC-SC axis at different maturation stages, as in pNFs.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005908","title":"Transcriptome analysis of endometrial organoids derived from patients with Mayer-Rokitansky-Küster-Hauser syndrome","description":"The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. The cause of the disease is still enigmatic. Here, we developed organoid cultures from endometrium found in uterine rudiment horns of MRKH patients. Phenotypically they share great similarity between healthy control organoids and are fully hormone responsive. Transcriptome analysis using RNA-seq identified possible disease-causing pathways altered in MRKH patients during development of the female reproductive tract. Thus, the organoid cultures provide a powerful research model for further insight into disease-causing alterations.","abstract":"The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. The cause of the disease is still enigmatic. Here, we developed organoid cultures from endometrium found in uterine rudiment horns of MRKH patients. Phenotypically they share great similarity between healthy control organoids and are fully hormone responsive. Transcriptome analysis using RNA-seq identified possible disease-causing pathways altered in MRKH patients during development of the female reproductive tract. Thus, the organoid cultures provide a powerful research model for further insight into disease-causing alterations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2021-12-30T16:53:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005909","title":"Rare occurrence of Aristolochic Acid Mutational Signatures in Oro-Gastrointestinal Tract Cancers","description":"Aristolochic Acids (AAs) are a family of carcinogenic phytochemical compounds commonly found in plants of Aristolochia and Asarum genus. Comprehensive genomic profiling of genitourinary and hepatobiliary cancers has highlighted the widespread prevalence of Aristolochic Acid (AA) signatures in cancer patients across parts of Asia, particularly in Taiwan. The aim of our study was to determine in Oro-Gastrointestinal Tract (OGITC) cancers, the prevalence, role and significance that AA plays as a driver of tumorigenesis as AA containing products are commonly administered orally. This would suggest a possible etiological relationship between cancers of OGITC. However, in this study the rarity of AA mutational signatures in OGITC suggests that AA is unlikely to drive carcinogenesis in OGITC through direct exposure. Our study is valuable to show that AA exposure is not an equal driver of tumorigenesis in different organs and represents an important piece of information in the field.","abstract":"Aristolochic Acids (AAs) are a family of carcinogenic phytochemical compounds commonly found in plants of Aristolochia and Asarum genus. Comprehensive genomic profiling of genitourinary and hepatobiliary cancers has highlighted the widespread prevalence of Aristolochic Acid (AA) signatures in cancer patients across parts of Asia, particularly in Taiwan. The aim of our study was to determine in Oro-Gastrointestinal Tract (OGITC) cancers, the prevalence, role and significance that AA plays as a driver of tumorigenesis as AA containing products are commonly administered orally. This would suggest a possible etiological relationship between cancers of OGITC. However, in this study the rarity of AA mutational signatures in OGITC suggests that AA is unlikely to drive carcinogenesis in OGITC through direct exposure. Our study is valuable to show that AA exposure is not an equal driver of tumorigenesis in different organs and represents an important piece of information in the field.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-04T08:13:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005910","title":"Genome-wide genotype data for 1,433 ni-Vanuatu","description":"Here, we generated genome-wide genotype data for 1,433 contemporary ni-Vanuatu and assessed their fine-scale genetic structure, in order to address central questions about the settlement of western Remote Oceania.","abstract":"Here, we generated genome-wide genotype data for 1,433 contemporary ni-Vanuatu and assessed their fine-scale genetic structure, in order to address central questions about the settlement of western Remote Oceania.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-04T15:36:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005911","title":"Epigenomic priming of immune genes implicates oligodendroglia in multiple sclerosissusceptibility","description":"Multiple sclerosis (MS) is characterized by a targeted attack on oligodendroglia (OLG)and associated myelin by immune cells, which are thought to be the main drivers of MS susceptibility. Assessing chromatin accessibility and the transcriptome simultaneously at the single cell level, we found that immune genes exhibit a primedchromatin state in mouse and human OLG in a non-disease context, compatible withrapid transitions to immune-competent states in MS.  We identified transcription factors as BACH1 and STAT1 involved in immune gene regulation in oligodendrocyteprecursor cells (OPCs). A subset of immune genes present bivalency of H3K4me3/H3K27me3 in OPCs, with Polycomb inhibition leading to their increased activation upon interferon-gamma (IFNg) treatment. Some MS susceptibility single-nucleotide polymorphisms (SNPs) overlap with these regulatory regions in mouse andhuman OLG, and treatment of mouse OPCs with IFNg leads to chromatin architecture remodeling at these loci and altered expression of interacting genes. Our data indicates that susceptibility for MS may involve OLG, which therefore constitute novel targets for immunological-based therapies for MS.","abstract":"Multiple sclerosis (MS) is characterized by a targeted attack on oligodendroglia (OLG)and associated myelin by immune cells, which are thought to be the main drivers of MS susceptibility. Assessing chromatin accessibility and the transcriptome simultaneously at the single cell level, we found that immune genes exhibit a primedchromatin state in mouse and human OLG in a non-disease context, compatible withrapid transitions to immune-competent states in MS.  We identified transcription factors as BACH1 and STAT1 involved in immune gene regulation in oligodendrocyteprecursor cells (OPCs). A subset of immune genes present bivalency of H3K4me3/H3K27me3 in OPCs, with Polycomb inhibition leading to their increased activation upon interferon-gamma (IFNg) treatment. Some MS susceptibility single-nucleotide polymorphisms (SNPs) overlap with these regulatory regions in mouse andhuman OLG, and treatment of mouse OPCs with IFNg leads to chromatin architecture remodeling at these loci and altered expression of interacting genes. Our data indicates that susceptibility for MS may involve OLG, which therefore constitute novel targets for immunological-based therapies for MS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-05T11:16:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005912","title":"Sequencing of an organoid biobank for childhood soft tissue sarcoma.","description":"Rhabdomyosarcomas are diverse tumors of mesenchymal origin and the most common childhood soft tissue sarcoma. Patients receive intense treatment with a nevertheless poor prognosis for high-risk patients. New therapy would benefit from additional preclinical models and their rapid establishment. Tumor organoid models (tumoroids) have so far only been established from epithelial cancers. Here, we describe generation and characterization of a collection of pediatric RMS tumoroids comprising all major subtypes.","abstract":"Rhabdomyosarcomas are diverse tumors of mesenchymal origin and the most common childhood soft tissue sarcoma. Patients receive intense treatment with a nevertheless poor prognosis for high-risk patients. New therapy would benefit from additional preclinical models and their rapid establishment. Tumor organoid models (tumoroids) have so far only been established from epithelial cancers. Here, we describe generation and characterization of a collection of pediatric RMS tumoroids comprising all major subtypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-05T11:19:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005913","title":"primary_DIPG_expression_profiles","description":null,"abstract":"In this study, we used RNA-sequencing gene expression profiling in order to characterize specific phenotypic traits in DIPG. Seventeen primary tumor samples stereotactically biopsied at diagnosis by neurosurgeons in the Necker-Enfants Malades hospital (Paris, France) and snap-frozen for RNA extraction and subsequent poly-A mRNA purification.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005914","title":"Target gene sequencing for human normal endometrial glands","description":"To elucidate the timing and mechanism of the clonal expansion of somatic mutations in cancer-associated genes in the normal endometrium, we conducted target sequencing of 112 genes for 1,298 endometrial glands and matched blood samples from 36 women. By collecting endometrial glands from different parts of the endometrium, we showed that multiple glands with the same somatic mutations occupied substantial areas of the endometrium. The 112 genes are as follows: ABCC1, ACRC, ANK3, ARHGAP35, ARID1A, ARID5B, ATCAY, ATM, ATR, BARD1, BCOR, BRCA1, BRCA2, BRD4, BRIP1, CAMTA1, CDC23, CDYL, CFAP54, CHD4, CHEK1, CHEK2, CTCF, CTNNB1, CUX1, DGKA, DISP2, DYNC2H1, EMSY, FAAP24, FAM135B, FAM175A, FAM65C, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, FAT1, FAT3, FBN2, FBXW7, FGFR2, FRG1, GPR50, HEATR1, HIST1H4B, HNRNPCL1, HOOK3, KIAA1109, KIF26A, KMT2B, KMT2C, KRAS, LAMA2, LRP1B, MLH1, MON2, MRE11A, MSH2, MSH6, MTOR, NBN, PALB2, PHEX, PIK3CA, PIK3R1, PLXNB2, PLXND1, PMS2, POLE, POLR3B, PPP2R1A, PTEN, PTPN13, RAD50, RAD51, RAD51B, RAD51C, RAD51D, RAD52, RAD54B, RAD54L, RICTOR, SACS, SIGLEC9, SLC19A1, SLX4, SPEG, STT3A, TAF1, TAF2, TAS2R31, TFAP2C, TNC, TONSL, TP53, TTC6, UBA7, VNN1, WT1, XIRP2, ZBED6, ZC3H13, ZFHX3, ZFHX4, ZMYM4.","abstract":"To elucidate the timing and mechanism of the clonal expansion of somatic mutations in cancer-associated genes in the normal endometrium, we conducted target sequencing of 112 genes for 1,298 endometrial glands and matched blood samples from 36 women. By collecting endometrial glands from different parts of the endometrium, we showed that multiple glands with the same somatic mutations occupied substantial areas of the endometrium. The 112 genes are as follows: ABCC1, ACRC, ANK3, ARHGAP35, ARID1A, ARID5B, ATCAY, ATM, ATR, BARD1, BCOR, BRCA1, BRCA2, BRD4, BRIP1, CAMTA1, CDC23, CDYL, CFAP54, CHD4, CHEK1, CHEK2, CTCF, CTNNB1, CUX1, DGKA, DISP2, DYNC2H1, EMSY, FAAP24, FAM135B, FAM175A, FAM65C, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, FAT1, FAT3, FBN2, FBXW7, FGFR2, FRG1, GPR50, HEATR1, HIST1H4B, HNRNPCL1, HOOK3, KIAA1109, KIF26A, KMT2B, KMT2C, KRAS, LAMA2, LRP1B, MLH1, MON2, MRE11A, MSH2, MSH6, MTOR, NBN, PALB2, PHEX, PIK3CA, PIK3R1, PLXNB2, PLXND1, PMS2, POLE, POLR3B, PPP2R1A, PTEN, PTPN13, RAD50, RAD51, RAD51B, RAD51C, RAD51D, RAD52, RAD54B, RAD54L, RICTOR, SACS, SIGLEC9, SLC19A1, SLX4, SPEG, STT3A, TAF1, TAF2, TAS2R31, TFAP2C, TNC, TONSL, TP53, TTC6, UBA7, VNN1, WT1, XIRP2, ZBED6, ZC3H13, ZFHX3, ZFHX4, ZMYM4.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-06T03:57:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005915","title":"ATACseq in blood-derived monocytes from CGD patients","description":null,"abstract":"We collected MACS-negatively isolated monocytes from fresh PBMCs from CGD patients. We applied ATACseq to characterize the changes in the epigenetic landscape of CGD monocytes.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005916","title":"A functional genomics approach in Tanzanian population identifies distinct genetic regulators of cytokine production compared to European population","description":null,"abstract":"Identification of genetic variants associated with induced cytokine production.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005917","title":"Targeted_NanoSeq_Pan_body","description":"Targeted NanoSeq across a range of human tissues using a custom-designed panel of ~200 genes to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across a wide range of tissues.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005918","title":"Targeted_NanoSeq_Synovium","description":"Targeted NanoSeq in synoviums from a number of donors, including donors with no past medical history of joint issues, as well as those with rheumatoid arthritis and osteoarthritis. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across a large number of synovium specimens.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005919","title":"Targeted_NanoSeq_Supernatants","description":"Targeted NanoSeq in epithelial cultures grown in-vitroes from healthy epithelium such as bladder urothelium and oral epithelia. Once in culture, samples obtained include the original colony and supernatants extracted containing cells at time points and different exposures. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across epithelial cultures temporally, and with exposures.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005920","title":"Targeted_NanoSeq_Sperm","description":"Targeted NanoSeq in sperm samples provided by healthy patients. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape in sperm samples obtained longitudinally.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-06T13:00:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005921","title":"Targeted_NanoSeq_Prostate","description":"Targeted NanoSeq in prostates from a number of donors, both healthy and those with benign prostatic hyperplasia. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across a large number of prostate specimens.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005922","title":"Targeted_NanoSeq_Pancreas","description":"Targeted NanoSeq in pancreases from a number of donors, primarily those without a known malignancy. Samples may contain pre-malignant histology and may also come from those with non-malignant diseases of the pancreas, such as diabetes mellitus. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across a large number of pancreatic specimens.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005923","title":"Targeted_NanoSeq_Liver","description":"Targeted NanoSeq in livers from a number of donors, including donors with no past medical history of liver issues, as well as those with diabetes mellitus, non-alcoholic fatty liver disease, alcoholic liver disease, and cirrhosis of other aetiology. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across a large number of liver specimens.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005924","title":"Targeted_NanoSeq_Granulocytes","description":"Targeted NanoSeq in granulocytes from a number of donors. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape in granulocytes from a number of donors.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005925","title":"Targeted_NanoSeq_Buccal","description":"Targeted NanoSeq in buccal epithelium obtained longitudinally from a number of donors. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across a large number of donors using buccal swabs.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-06T13:26:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005926","title":"Genomic determination for Homologous Recombination Deficiency (HRD) by shallow Whole Genome Sequencing (sWGS)","description":"Genomic determination for Homologous Recombination Deficiency (HRD) by shallow Whole Genome Sequencing (sWGS) with shallowHRD (PMID : 32315385) on 55 triple-negative breast cancer Patient Derived-Xenograft (PDX) treated with platinum.","abstract":"Genomic determination for Homologous Recombination Deficiency (HRD) by shallow Whole Genome Sequencing (sWGS) with shallowHRD (PMID : 32315385) on 55 triple-negative breast cancer Patient Derived-Xenograft (PDX) treated with platinum.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-06T15:06:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005927","title":"Targeted_NanoSeq_Brain_and_Neurons","description":"Targeted NanoSeq in a number of different brain regions and isolated neurons, from a number of donors. Samples are obtained from patients without a neurological medical history, and those with known Alzheimer's dementia. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape in the brain and nervous system, across a number of donors.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005928","title":"Targeted_NanoSeq_Bladder","description":"Targeted NanoSeq in bladders from a number of donors, including donors with and without malignancy. Samples may contain pre-malignant histology A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across a large number of bladder specimens.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005929","title":"Targeted_NanoSeq_Atherosclerosis","description":"Targeted NanoSeq in healthy and atherosclerotic blood vessels from a number of donors. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across a large number of appendix specimens.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005930","title":"Targeted_NanoSeq_Appendix","description":"Targeted NanoSeq on appendix samples obtained from healthy donors and those with a DNA repair deficiency. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape in appendices from a range of healthy donors, and those with a DNA repair deficiency.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005931","title":"COVID-19 Severity of First Wave of Infection for Severe Patients in Madrid","description":"Through thorough exclusion criteria and deep phenotypic characterisation for a Madrid-based population we intend to find enrichment of gene mutations associated to severity. In addition we will look for statistically overrepresented annotation of particular phenotypes (a controlled vocabulary specifically developed for this project) that associate them to affected genes in our patient sample.","abstract":"Through thorough exclusion criteria and deep phenotypic characterisation for a Madrid-based population we intend to find enrichment of gene mutations associated to severity. In addition we will look for statistically overrepresented annotation of particular phenotypes (a controlled vocabulary specifically developed for this project) that associate them to affected genes in our patient sample.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-07T12:15:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005932","title":"Methylation profiling of osteoblastomas and their mimics","description":"Here, we set out to comprehensively characterize a series of 77 osteoblastomas by immunohistochemistry, fluorescence in-situ hybridization as well as copy number and methylation profiling and compared our findings to histologic mimics.","abstract":"Here, we set out to comprehensively characterize a series of 77 osteoblastomas by immunohistochemistry, fluorescence in-situ hybridization as well as copy number and methylation profiling and compared our findings to histologic mimics.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-07T15:51:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005933","title":"Myoepithelial progenitors as founder cells of hyperplastic human breast lesions upon PIK3CA transformation","description":"The myoepithelial (MEP) lineage of human breast comprises bipotent and multipotent progenitors in ducts and terminal duct lobular units (TDLUs). We here assess whether this heterogeneity impacts on oncogenic PIK3CA transformation. Single cell RNA sequencing (scRNA-seq) and multicolor imaging reveal that terminal ducts represent the most enriched source of cells with ductal MEP markers including a-smooth muscle actin (a-SMA), keratin K14, K17 and CD200. Furthermore, we find neighboring CD200high and CD200low progenitors within terminal ducts. When sorted and kept in ground state conditions, their CD200low and CD200high phenotypes are preserved. Upon differentiation, progenitors remain multipotent and bipotent, respectively.  Immortalized progenitors are transduced with shp53 and mutant PIK3CA. Upon transplantation, CD200low MEP progenitors distinguish from CD200high by the formation of multilayered structures with a hyperplastic inner layer of luminal epithelial cells. We suggest a model with spatially distributed MEP progenitors as founder cells of biphasic breast lesions with implications for early detection and prevention strategies.","abstract":"The myoepithelial (MEP) lineage of human breast comprises bipotent and multipotent progenitors in ducts and terminal duct lobular units (TDLUs). We here assess whether this heterogeneity impacts on oncogenic PIK3CA transformation. Single cell RNA sequencing (scRNA-seq) and multicolor imaging reveal that terminal ducts represent the most enriched source of cells with ductal MEP markers including a-smooth muscle actin (a-SMA), keratin K14, K17 and CD200. Furthermore, we find neighboring CD200high and CD200low progenitors within terminal ducts. When sorted and kept in ground state conditions, their CD200low and CD200high phenotypes are preserved. Upon differentiation, progenitors remain multipotent and bipotent, respectively.  Immortalized progenitors are transduced with shp53 and mutant PIK3CA. Upon transplantation, CD200low MEP progenitors distinguish from CD200high by the formation of multilayered structures with a hyperplastic inner layer of luminal epithelial cells. We suggest a model with spatially distributed MEP progenitors as founder cells of biphasic breast lesions with implications for early detection and prevention strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-09T09:26:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005934","title":"Effect_of_ADCY7_risk_variant_on_immune_cells","description":"we hypothesize that genetic variants affecting genes involved in cAMP metabolism could lead to an abnormal inflammatory response, contributing to the increased risk of developing IBD. Our group has reported a missense variant in an enzyme called adenylate cyclase 7(ADCY7). This missense variant (p.Asp439Glu, rs78534766) doubles the risk of ulcerative colitis (OR=2.19) and is predicted to alter protein function (PolyPhen=1). In addition to ADCY7, other IBD risk variants have been described in intronic regions of ADCY3 (ADCY7 isoenzyme).\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We aim to define the role of rs78534766 (ADCY7 missense variant, A) and ADCY3 risk locus (tagged by rs11676272, G) in gene expression in immune cells. Our preliminary data show that indels induced by CRISPR/Cas9 on ADCY7 gene in T cells lead to an increase in TNF-α production, suggesting a possible role of this gene in cytokine regulation and/or cell activation. Here, we propose to analyse the transcriptional consequences of carrying ADCY7 risk variant (rs78534766, A) or ADCY3 risk locus (12 genetic variants in high LD R2 &gt;0.95 and tagged by rs11676272, G- eQTL for ADCY3 in T cells ) in blood cells.\nWe will sort neutrophils, T cells and monocytes from peripheral blood of risk variant carriers or non-carriers followed by bulk RNA-sequencing. These experiments will inform us on: a) the blood cell type(s) in which these risk variants are active and b) which biological pathways these genetic variants modulate. In parallel, we will use blood samples from the same individuals to compare secretion of TNF-α (as suggested by CRISPR experiments) and production of cAMP (measurement of ADCY7 and ADCY3 activity). We have recently been granted the approval from the NIHR BioResource for Translational Research to recruit five volunteers for each genotype (due to low frequency of risk allele in rs78534766, heterozygous will be recalled) for a pilot experiment.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005935","title":"The European MAPPYACTS trial: Precision Medicine Program in Pediatric and Adolescent Patients with Recurrent Malignancies","description":"MAPPYACTS (NCT02613962) is an international prospective precision medicine trial aiming to define tumor molecular profiles in pediatric patients with recurrent/refractory malignancies, in order to suggest the most adapted salvage treatment.\nFrom February 2016 to July 2020, 787 patients were included in France, Italy, Ireland and Spain. At least one genetic alteration leading to targeted treatment suggestion was identified in 436 patients (69%) with successful sequencing; 10% of these were considered \"ready for routine use\". Of 356 patients with follow-up beyond 12 months, 107 (30%) received one or more matched targeted therapies, 56% of them within early clinical trials, mainly in the AcSé-ESMART platform trial (NCT02813135). Overall, matched treatment resulted in a 17% objective response rate, those of patients with \"ready for routine use\" alterations was 38%. In patients with extra-cerebral tumors, 76% of actionable alterations detected in tumor tissue were also identified in circulating cell free DNA (cfDNA).","abstract":"MAPPYACTS (NCT02613962) is an international prospective precision medicine trial aiming to define tumor molecular profiles in pediatric patients with recurrent/refractory malignancies, in order to suggest the most adapted salvage treatment.\nFrom February 2016 to July 2020, 787 patients were included in France, Italy, Ireland and Spain. At least one genetic alteration leading to targeted treatment suggestion was identified in 436 patients (69%) with successful sequencing; 10% of these were considered \"ready for routine use\". Of 356 patients with follow-up beyond 12 months, 107 (30%) received one or more matched targeted therapies, 56% of them within early clinical trials, mainly in the AcSé-ESMART platform trial (NCT02813135). Overall, matched treatment resulted in a 17% objective response rate, those of patients with \"ready for routine use\" alterations was 38%. In patients with extra-cerebral tumors, 76% of actionable alterations detected in tumor tissue were also identified in circulating cell free DNA (cfDNA).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-10T16:33:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005936","title":"The genomic landscape of early-stage ovarian high grade serous carcinoma","description":null,"abstract":"Purpose: Ovarian high grade serous carcinoma (HGSC) is usually diagnosed at late stage. We investigated whether late-stage HGSC has unique genomic characteristics consistent with acquisition of evolutionary advantage compared to early-stage tumours.\nExperimental Design: We performed targeted next generation sequencing and shallow whole genome sequencing (sWGS) on pre-treatment samples from 43 patients with FIGO stage I–IIA HGSC to investigate somatic mutations and copy number alterations (SCNA). We compared results to pre-treatment samples from 52 stage IIIC/IV HGSC patients from the BriTROC-1 study.\nResults: Age of diagnosis did not differ between early-stage and late-stage patients (median 61.3 years vs 62.3 years respectively). TP53 mutations were near-universal in both cohorts (89% early- stage, 100% late-stage) and there were no significant differences in the rates of other somatic mutations, including BRCA1 and BRCA2. We also did not observe cohort-specific focal SCNA that could explain biological behaviour. However, ploidy was higher in late-stage (median 3.0) than early-stage (median 1.9) samples. Copy number (CN) signature exposures were significantly different between cohorts, with greater relative signature 3 exposure in early-stage and greater signature 4 in late-stage. Unsupervised clustering based on CN signatures identified three clusters that were prognostic.\nConclusions: Early stage and late stage HGSC have highly similar patterns of mutation and focal SCNA. However, copy number signature analysis showed that late-stage disease has distinct signature exposures consistent with whole genome duplication. Further analyses will be required to ascertain whether these differences reflect genuine biological differences between early and late-stage or simply time-related markers of evolutionary fitness.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005937","title":"Paired healthy & tumor organoid Biobank _B16PON","description":"B16PON consists  of  a panel of  organoids (three-dimensional cell cultures) of premalignant epithelial cells of  the colon and rectum. These organoids are derived from adenomas that are resected during a colonoscopy procedure. These can be propagated indefinitely and can be used to answer different research questions.","abstract":"B16PON consists  of  a panel of  organoids (three-dimensional cell cultures) of premalignant epithelial cells of  the colon and rectum. These organoids are derived from adenomas that are resected during a colonoscopy procedure. These can be propagated indefinitely and can be used to answer different research questions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-11T11:37:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005938","title":"Analysis of recent shared ancestry in a familial cohort identifies coding and noncoding autism spectrum disorder variants","description":null,"abstract":"We performed whole genome sequencing (WGS) in an ASD cohort of 68 individuals from 22 families enriched for recent shared ancestry. We identified an average of 3.07 million variants per genome, of which an average of 112,512 were rare. We mapped runs of homozygosity (ROHs) in affected individuals and found an average genomic homozygosity of 9.65%, consistent with expectations for multiple generations of consanguineous unions. We identified potentially pathogenic rare exonic or splice site variants in 12 known (including KMT2C, SCN1A, SPTBN1, SYNE1, ZNF292) and 12 candidate (including CHD5, GRB10, PPP1R13B) ASD genes. Furthermore, we annotated noncoding variants in ROHs with brain-specific regulatory elements and identified putative disease-causing variants within brain-specific promoters and enhancers for 5 known ASD and neurodevelopmental disease genes (ACTG1, AUTS2, CTNND2, CNTNAP4, SPTBN4). We also identified copy number variants in two known ASD and neurodevelopmental disease loci in two affected individuals. In total we identified potentially etiological variants in known ASD or neurodevelopmental disease genes for ~61% (14/23) of affected individuals. We combined WGS with homozygosity mapping and regulatory element annotations to identify candidate ASD variants.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005939","title":"Human induced pluripotent stem cells display a similar mutation burden as embryonic pluripotent cells in vivo","description":"Induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine, but genetic instability is a major concern. Embryonic pluripotent cells also accumulate mutations during early development, but how this relates to the mutation burden in iPSCs remains unknown. Here, we directly compared the mutation burden of cultured iPSCs with their isogenic embryonic cells during human embryogenesis. We generated developmental lineage trees of human fetuses by phylogenetic inference from somatic mutations in the genomes of multiple stem cells, which were derived from different germ layers. Using this approach, we characterized the mutations acquired pre-gastrulation and found a rate of 1.65 mutations per cell division. When cultured in hypoxic conditions, iPSCs generated from fetal stem cells of the assessed fetuses displayed a similar mutation rate and spectrum. Our results show that iPSCs maintain a genomic integrity during culture at a similar degree as their pluripotent counterparts do in vivo.","abstract":"Induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine, but genetic instability is a major concern. Embryonic pluripotent cells also accumulate mutations during early development, but how this relates to the mutation burden in iPSCs remains unknown. Here, we directly compared the mutation burden of cultured iPSCs with their isogenic embryonic cells during human embryogenesis. We generated developmental lineage trees of human fetuses by phylogenetic inference from somatic mutations in the genomes of multiple stem cells, which were derived from different germ layers. Using this approach, we characterized the mutations acquired pre-gastrulation and found a rate of 1.65 mutations per cell division. When cultured in hypoxic conditions, iPSCs generated from fetal stem cells of the assessed fetuses displayed a similar mutation rate and spectrum. Our results show that iPSCs maintain a genomic integrity during culture at a similar degree as their pluripotent counterparts do in vivo.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-12T06:42:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005940","title":"Molecular analysis in bowel malignancies in cancer survivors vs. primary malignancies","description":null,"abstract":"Background: Hodgkin lymphoma (HL) and testicular cancer (TC) survivors have an increased risk of developing second primary bowel malignancies (both colorectal cancer (CRC) and small bowel adenocarcinoma (SBA)). We aimed to determine differences in genetic characteristics of second primary bowel malignancies and primary bowel malignancies. \nMethods: Copy number aberrations (CNAs) generated by low-coverage whole-genome sequencing (WGS) were collected from previous studies of second primary CRC (HL survivors, n=39), primary CRC (n=90) and primary SBA (n=14). In addition, seven new samples of second primary SBA from HL (n=3) or TC (n=5) survivors, identified in the Dutch national pathology registry (PALGA), were available for low-coverage WGS. \nResults: Overall, CNA patterns observed in second primary bowel malignancies were similar to those in primary bowel malignancies. Losses of 21q22.2 were observed more frequently (p=0.057) in second primary CRC compared with primary CRC, while in second primary SBA gains of 10p15.3-15.1 and losses of 18q12.1-23 were significantly more frequent detected compared with primary SBA. \nConclusions: Second primary CRC and SBA show comparable genome wide CNAs to those in primary CRC and SBA, respectively. This suggests that part of the pathogenesis of second primary tumours in these cancer survivors is similar to those of primary CRC and SBA in general, despite the exposure to DNA damaging treatments received for earlier HL and TC.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-13T09:36:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005941","title":"T-cell reconstitution after reduced dose ATLG induction in kidney transplant recipients","description":"Pre-sensitized kidney transplant recipients have a higher risk for rejection following kidney transplantation and therefore receive a lymphodepletional induction therapy with anti human T-lymphocyte globulin (ATLG). The time course of lymphocyte reconstitution with regards to overall and donor-reactive T-cell receptor (TCR) specificity remains elusive.  In this study we aimed to describe the TCR repertoire in a reduced dose ATLG regimen making it possible to evaluate shifts in the shape of the immune repertoire and to detect the reappearance of donor-reactive T-cells following reduced lymphodepletional induction therapy.","abstract":"Pre-sensitized kidney transplant recipients have a higher risk for rejection following kidney transplantation and therefore receive a lymphodepletional induction therapy with anti human T-lymphocyte globulin (ATLG). The time course of lymphocyte reconstitution with regards to overall and donor-reactive T-cell receptor (TCR) specificity remains elusive.  In this study we aimed to describe the TCR repertoire in a reduced dose ATLG regimen making it possible to evaluate shifts in the shape of the immune repertoire and to detect the reappearance of donor-reactive T-cells following reduced lymphodepletional induction therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-14T16:43:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005942","title":"snRNA-seq of Acute-Isolated Human Brain","description":"We find a similar gene signature is present in post-mortem microglia and astrocytes, across all snRNA-seq datasets analyzed, although it is highly variable between subjects.  Through the use of acutely-resected neurosurgical tissue, we reveal that a similar signature can be detected in microglia following prolonged exposure to room temperature.  These results suggest that the presence of this signature in post-mortem brain samples may be the result of a combination of acute pre-mortem (agonal state, cause of death, comorbidities, etc.) and post-mortem (post-mortem interval (PMI), storage time, RNA quality, etc.) variables.","abstract":"We find a similar gene signature is present in post-mortem microglia and astrocytes, across all snRNA-seq datasets analyzed, although it is highly variable between subjects.  Through the use of acutely-resected neurosurgical tissue, we reveal that a similar signature can be detected in microglia following prolonged exposure to room temperature.  These results suggest that the presence of this signature in post-mortem brain samples may be the result of a combination of acute pre-mortem (agonal state, cause of death, comorbidities, etc.) and post-mortem (post-mortem interval (PMI), storage time, RNA quality, etc.) variables.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005943","title":"Long cell-free DNA molecules in maternal plasma 2","description":"Long cell-free DNA molecules in maternal plasma 2","abstract":"Long cell-free DNA molecules in maternal plasma 2","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005944","title":"In this study, blood-brain barrier (BBB)-forming brain endothelial-like cells were generated from apolipoprotein E gene allele E4 (APOE4, high AD risk) and allele E3 (APOE3, lower AD risk) carrying patient-derived induced pluripotent stem cells (iPSCs). Cells were subsequently exposed to focused ultrasound and microbubbles (FUS+MB) to induce BBB opening and their transcriptome analysed. RNA sequencing (RNA-seq) results demonstrated minimal changes in the gene expression following FUS+MB suggesting safety of FUS+MB application in the clinical setting.","description":"The blood-brain barrier (BBB) is a major impediment to therapeutic intracranial drug delivery for the treatment of neurodegenerative diseases, including Alzheimer’s disease (AD). Focused ultrasound applied together with microbubbles (FUS+MB) is a novel technique to transiently open the BBB and increase drug delivery. Evidence suggests that FUS+MB is safe, however the effects of FUS+MB on human BBB cells, especially in relation to AD, remain sparsely investigated. Here we developed a human sporadic AD BBB cell platform to investigate the effects of FUS+MB on BBB cells and screen for the delivery of two potentially therapeutic AD antibodies. We generated BBB cells from apolipoprotein E gene allele E4 (APOE4, high AD risk) and allele E3 (APOE3, lower AD risk) carrying patient-derived induced pluripotent stem cells (iPSCs). We utilized this robust and reproducible platform to demonstrate increased delivery of potentially therapeutic antibodies across the BBB, including an analogue of Aducanumab (AduhelmTM) following FUS+MB treatment. Our results also demonstrate the safety of FUS+MB indicated by minimal changes in the cell transcriptome as well as little or no changes in cell viability and inflammatory responses within first 24 h post FUS+MB, with potentially important implications in a clinical setting. Finally, we report a more physiologically relevant hydrogel-based 2.5D BBB model as a key development for FUS+MB-mediated drug delivery screening, with potentially higher translational utility. Our results provide an important advancement for identifying FUS+MB-deliverable drugs and screening for cell- and patient-specific effects of FUS+MB, accelerating its use as a therapy in AD.","abstract":"The blood-brain barrier (BBB) is a major impediment to therapeutic intracranial drug delivery for the treatment of neurodegenerative diseases, including Alzheimer’s disease (AD). Focused ultrasound applied together with microbubbles (FUS+MB) is a novel technique to transiently open the BBB and increase drug delivery. Evidence suggests that FUS+MB is safe, however the effects of FUS+MB on human BBB cells, especially in relation to AD, remain sparsely investigated. Here we developed a human sporadic AD BBB cell platform to investigate the effects of FUS+MB on BBB cells and screen for the delivery of two potentially therapeutic AD antibodies. We generated BBB cells from apolipoprotein E gene allele E4 (APOE4, high AD risk) and allele E3 (APOE3, lower AD risk) carrying patient-derived induced pluripotent stem cells (iPSCs). We utilized this robust and reproducible platform to demonstrate increased delivery of potentially therapeutic antibodies across the BBB, including an analogue of Aducanumab (AduhelmTM) following FUS+MB treatment. Our results also demonstrate the safety of FUS+MB indicated by minimal changes in the cell transcriptome as well as little or no changes in cell viability and inflammatory responses within first 24 h post FUS+MB, with potentially important implications in a clinical setting. Finally, we report a more physiologically relevant hydrogel-based 2.5D BBB model as a key development for FUS+MB-mediated drug delivery screening, with potentially higher translational utility. Our results provide an important advancement for identifying FUS+MB-deliverable drugs and screening for cell- and patient-specific effects of FUS+MB, accelerating its use as a therapy in AD.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-17T02:34:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005945","title":"Combination therapies to inhibit LCK tyrosine kinase and mTOR signaling in T-cell Acute Lymphoblastic Leukemia","description":"Relapse and refractory T cell acute lymphoblastic leukemia (T-ALL) has a poor prognosis and new combination therapies are sorely needed. This work uncovered potent drug synergies between AKT/mTORC1 inhibitors and the general tyrosine kinase-inhibitor, dasatinib. The combination effectively curbed T-ALL growth in human cell lines and primary human T-ALL samples, and was well tolerated and effective in suppressing leukemia growth in patient-derived xenografts grown in mice. Mechanistically, dasatinib inhibited phosphorylation and activation of the lymphocyte-specific protein tyrosine kinase (LCK) to blunt the T-cell receptor (TCR) signaling pathway and when complexed with mTORC1 inhibition, induced potent T-ALL cell killing through reducing MCL-1 protein expression. Analysis of responses across T-ALL subtypes and association with specific genetic mutations or expression patterns failed to identify any obvious biomarkers or correlations in predicting therapy responses, although there appeared to be a trend toward higher TCR/LCK pathway activity in samples that exhibited synergistic therapy responses.","abstract":"Relapse and refractory T cell acute lymphoblastic leukemia (T-ALL) has a poor prognosis and new combination therapies are sorely needed. This work uncovered potent drug synergies between AKT/mTORC1 inhibitors and the general tyrosine kinase-inhibitor, dasatinib. The combination effectively curbed T-ALL growth in human cell lines and primary human T-ALL samples, and was well tolerated and effective in suppressing leukemia growth in patient-derived xenografts grown in mice. Mechanistically, dasatinib inhibited phosphorylation and activation of the lymphocyte-specific protein tyrosine kinase (LCK) to blunt the T-cell receptor (TCR) signaling pathway and when complexed with mTORC1 inhibition, induced potent T-ALL cell killing through reducing MCL-1 protein expression. Analysis of responses across T-ALL subtypes and association with specific genetic mutations or expression patterns failed to identify any obvious biomarkers or correlations in predicting therapy responses, although there appeared to be a trend toward higher TCR/LCK pathway activity in samples that exhibited synergistic therapy responses.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-18T07:31:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005946","title":"HCA_Reproductive_Paediatric_Vento_RNA","description":"HCA Reproductive Paediatric Vento RNA Managed Access","abstract":"The goal of this study is to elucidate driving signals of the development of the gonads during childhood. Gonadal differentiation starts during fetal development but it is not fully functional until puberty. To understand the molecular mechanisms influencing the differentiation of the gonads after birth, we aim to construct a detailed single-cell atlas and spatial map of the human gonads.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005947","title":"Patient-derived organoids_Vumc","description":null,"abstract":"VUmc_organoids consists  of a panel of  organoids (three-dimensional cell cultures) of both normal, premalignant and cancer epithelial cells of  the colon. These organoids were resected during a colonoscopy procedure or a surgical procedure. These organoids, derived from tumor as well as healthy tissue, can be propagated indefinitely and can be used to answer different research questions.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-18T12:22:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005948","title":"RNA-seq on patient-derived, stage II, CRC cell lines","description":"The gut microbiome is a key player in the immunomodulatory and pro-tumorigenic microenvironment in colorectal cancer (CRC). It is well established that Fusobacterium’s virulence factors are responsible for its pro-tumorigenic properties, however the role of its metabolic cross-talk with the tumor remains unexplored. Here we use in vitro, in vivo, and in silico methods to describe a novel microbe-host interaction keystone: formate. Omics data reveals molecular signatures, linking a metabolically driven CRC phenotype with Fusobacteria. We observed a metabolic shift towards increased F. nucleatum formate secretion in gut-on-chip model co-cultures with patient-derived CRC cells, along with an accelerated cancer glutamine metabolism. We show that high formate levels trigger AhR signaling, increase cancer stemness and cellular invasion. Finally, we observed an expansion of Th17 cells accompanying F. nucleatum-induced tumorigenesis. Moving beyond observational studies, we applied new experimental approaches for gaining ecosystem-level mechanistic understanding of F. nucleatum’s role in cancer pathogenesis.","abstract":"The gut microbiome is a key player in the immunomodulatory and pro-tumorigenic microenvironment in colorectal cancer (CRC). It is well established that Fusobacterium’s virulence factors are responsible for its pro-tumorigenic properties, however the role of its metabolic cross-talk with the tumor remains unexplored. Here we use in vitro, in vivo, and in silico methods to describe a novel microbe-host interaction keystone: formate. Omics data reveals molecular signatures, linking a metabolically driven CRC phenotype with Fusobacteria. We observed a metabolic shift towards increased F. nucleatum formate secretion in gut-on-chip model co-cultures with patient-derived CRC cells, along with an accelerated cancer glutamine metabolism. We show that high formate levels trigger AhR signaling, increase cancer stemness and cellular invasion. Finally, we observed an expansion of Th17 cells accompanying F. nucleatum-induced tumorigenesis. Moving beyond observational studies, we applied new experimental approaches for gaining ecosystem-level mechanistic understanding of F. nucleatum’s role in cancer pathogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-18T12:36:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005949","title":"Overexpression of the miR-17-92 cluster in colorectal adenoma organoids induces a carcinoma-like genotype","description":null,"abstract":"Gain of chromosome arm 13q is one of the most prevalent DNA copy number alterations associated with colorectal adenoma-to-carcinoma progression. The oncogenic miR-17-92 cluster, located at 13q, was found to be overexpressed in colorectal cancer and in adenomas harboring 13q gain. However, to what extent overexpression of this group of microRNAs actually drives progression to cancer remains to be resolved. Therefore, we aimed to clarify the role of miR-17-92 cluster in the progression from colorectal adenoma to carcinoma.\nIn human colorectal adenoma organoids without 13q gain, the miR-17-92 cluster was overexpressed and downstream effects on mRNA expression investigated, along with functional effects in vitro and in vivo. \nComparison of mRNA sequencing results of organoids overexpressing miR-17-92 and cultures transduced with control vector, revealed a miR-17-92 expression signature. This signature appeared to be enriched in an independent series of colorectal cancers and adenomas tissues with 13q gain, confirming that miR-17-92 expression is associated with malignant progression. However, an increase in proliferation rate was not observed in miR-17-92 overexpressing adenoma organoids in vitro. In addition, subcutaneous injection of these organoids in immunodeficient mice was insufficient to cause tumor outgrowth. \nTransfecting miR-17-92 cluster in human colon adenoma organoids induces an expression signature that proved to be enriched in both adenomas with 13q gain and in colorectal cancers, supporting its role as a driver of 13q gain. However, overexpression of miR-17-92 alone is not sufficient to transform colorectal adenoma cells into a malignant phenotype.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-18T12:44:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005950","title":"The Proteogenomic Subtypes of Acute Myeloid Leukemia","description":"Acute myeloid leukemia (AML) is an aggressive blood cancer with poor prognosis. We report a comprehensive proteogenomic analysis of bone-marrow biopsies from 252 uniformly treated AML patients to elucidate the molecular pathophysiology of AML in order to inform future diagnostic and therapeutic approaches. In addition to in-depth quantitative proteomics, our analysis includes cytogenetic profiling and DNA/RNA sequencing. We identify five proteomic AML subtypes, each reflecting specific biological features spanning genomic boundaries. Two of these proteomic subtypes correlate with patient outcome, but none are exclusively associated with specific genomic aberrations. Remarkably, one subtype (Mito-AML), which is only captured in the proteome, is characterized by high expression of mitochondrial proteins and confers poor outcome, with reduced remission rate and shorter overall survival upon treatment with intensive induction chemotherapy. Functional analyses reveal that Mito-AML is metabolically wired towards stronger complex I dependent respiration and is more responsive to treatment with the BCL2 inhibitor venetoclax.","abstract":"Acute myeloid leukemia (AML) is an aggressive blood cancer with poor prognosis. We report a comprehensive proteogenomic analysis of bone-marrow biopsies from 252 uniformly treated AML patients to elucidate the molecular pathophysiology of AML in order to inform future diagnostic and therapeutic approaches. In addition to in-depth quantitative proteomics, our analysis includes cytogenetic profiling and DNA/RNA sequencing. We identify five proteomic AML subtypes, each reflecting specific biological features spanning genomic boundaries. Two of these proteomic subtypes correlate with patient outcome, but none are exclusively associated with specific genomic aberrations. Remarkably, one subtype (Mito-AML), which is only captured in the proteome, is characterized by high expression of mitochondrial proteins and confers poor outcome, with reduced remission rate and shorter overall survival upon treatment with intensive induction chemotherapy. Functional analyses reveal that Mito-AML is metabolically wired towards stronger complex I dependent respiration and is more responsive to treatment with the BCL2 inhibitor venetoclax.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-18T12:57:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005951","title":"RNA sequencing of 12 NSCLC samples from 4 patients at MDACC","description":"Multi-region RNA sequencing of 12 NSCLC samples from 4 patients at MDACC","abstract":"Multi-region RNA sequencing of 12 NSCLC samples from 4 patients at MDACC","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-18T23:45:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005952","title":"Tumor-intrinsic expression of the autophagy gene Atg16l1 suppresses anti-tumor immunity in colorectal cancer","description":"The vast majority of colorectal cancer (CRC) patients fail to respond to immune checkpoint inhibitors (ICI). Understanding tumor-intrinsic determinants of immunotherapy resistance is critical to improve CRC patient outcomes. Here, we demonstrate that transcript levels of the core autophagy gene ATG16L1 are prognostic of poor outcome and predictive of ICI resistance in late-stage CRC. Deletion of Atg16l1 in murine CRC organoids markedly inhibited tumor growth in primary and metastatic niches in syngeneic hosts. ATG16L1 deficiency rendered CRC organoids more responsive to interferon (IFN) signaling and enhanced programmed cell death while decreasing tumor stem-like populations. IFN hypersensitivity consequently promoted cytotoxic anti-tumor immunity in vivo. In IMblaze370, a large phase III clinical trial of anti-PD-L1 in advanced metastatic CRC, low ATG16L1 levels identified patients with increased lymphocyte infiltration and improved outcome in a KRAS mutant setting. This work reveals autophagy as a clinically relevant immunosuppressive mechanism in CRC and provides a rationale for autophagy inhibition to boost immunotherapy responses in the clinic.","abstract":"The vast majority of colorectal cancer (CRC) patients fail to respond to immune checkpoint inhibitors (ICI). Understanding tumor-intrinsic determinants of immunotherapy resistance is critical to improve CRC patient outcomes. Here, we demonstrate that transcript levels of the core autophagy gene ATG16L1 are prognostic of poor outcome and predictive of ICI resistance in late-stage CRC. Deletion of Atg16l1 in murine CRC organoids markedly inhibited tumor growth in primary and metastatic niches in syngeneic hosts. ATG16L1 deficiency rendered CRC organoids more responsive to interferon (IFN) signaling and enhanced programmed cell death while decreasing tumor stem-like populations. IFN hypersensitivity consequently promoted cytotoxic anti-tumor immunity in vivo. In IMblaze370, a large phase III clinical trial of anti-PD-L1 in advanced metastatic CRC, low ATG16L1 levels identified patients with increased lymphocyte infiltration and improved outcome in a KRAS mutant setting. This work reveals autophagy as a clinically relevant immunosuppressive mechanism in CRC and provides a rationale for autophagy inhibition to boost immunotherapy responses in the clinic.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-20T02:18:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005953","title":"Targeted sequencing of diffuse large B-cell lymphoma tumour samples from the UK's Haematological Malignancy Research Network","description":"The UK’s Haematological Malignancy Research Network (www.HMRN.org) was established in 2004 to provide robust generalizable data to inform clinical practice and research.  HMRN is a collaboration between researchers in the Epidemiology &amp;amp; Statistics Group (ECSG) at the University of York, a unified Clinical Network operating across 14 hospitals, and an integrated Haematological Malignancy Diagnostic Service (HMDS) in Leeds. \n \nCovering a population of around 4 million, HMRN collects detailed information about all patients diagnosed with a haematological malignancy within the HMRN region, accruing around 2,400 new diagnoses each year. The population has a similar socio-demographic profile to the country as a whole, and HMRN’s maturing data present an increasingly valuable resource to address real questions of concern to haematologists, commissioners and health service researchers – locally, nationally and internationally.\n \nThis study forms part of a larger project employing targeted exome sequencing on tumour samples from patients diagnosed with a variety of both lymphoid and myeloid malignancies. The results for samples collected from 928 diffuse large B-cell lymphoma patients, diagnosed within HMRN from 2005 to 2012, are provided.","abstract":"The UK’s Haematological Malignancy Research Network (www.HMRN.org) was established in 2004 to provide robust generalizable data to inform clinical practice and research.  HMRN is a collaboration between researchers in the Epidemiology &amp;amp; Statistics Group (ECSG) at the University of York, a unified Clinical Network operating across 14 hospitals, and an integrated Haematological Malignancy Diagnostic Service (HMDS) in Leeds. \n \nCovering a population of around 4 million, HMRN collects detailed information about all patients diagnosed with a haematological malignancy within the HMRN region, accruing around 2,400 new diagnoses each year. The population has a similar socio-demographic profile to the country as a whole, and HMRN’s maturing data present an increasingly valuable resource to address real questions of concern to haematologists, commissioners and health service researchers – locally, nationally and internationally.\n \nThis study forms part of a larger project employing targeted exome sequencing on tumour samples from patients diagnosed with a variety of both lymphoid and myeloid malignancies. The results for samples collected from 928 diffuse large B-cell lymphoma patients, diagnosed within HMRN from 2005 to 2012, are provided.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-20T08:20:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005954","title":"RNA-sequencing data from metastatic Castration-Resistant Prostate Cancer (mCRPC)","description":"The goal of this study is to characterize the transcriptional landscape of advanced prostate cancer","abstract":"The goal of this study is to characterize the transcriptional landscape of advanced prostate cancer","study_type":"Other","pubmed_ids":[30033370,30918106,30928160,34554200],"external_links":null,"is_released":true,"released_date":"2022-01-20T08:33:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005955","title":"Monocyte and macrophage lipid accumulation results in downregulated type-I interferon responses","description":"Macrophages are critical components of atherosclerotic lesions and their pro- and anti-inflammatory responses influence atherogenesis. Type-I interferons (IFNs) are cytokines that play an essential role in antiviral responses and inflammatory activation and have been shown to promote atherosclerosis. Although the impact of type-I IFNs on macrophage foam cell formation is well-documented, the effect of lipid accumulation in monocytes and macrophages on type-I IFN responses remains unknown. Here we examined IFN stimulated (ISG) and non-ISG inflammatory gene expression in mouse and human macrophages that were loaded with acetylated LDL (acLDL), as a model for foam cell formation. We found that acLDL loading in mouse and human macrophages specifically suppressed expression of ISGs and IFN-β secretion, but not other pro-inflammatory genes. The downregulation of ISGs could be rescued by exogenous IFN-β supplementation. Activation of the cholesterol-sensing nuclear liver X receptor (LXR) recapitulated the cholesterol-initiated type-I IFN suppression. Additional analyses of murine in vitro and in vivo generated foam cells confirmed the suppressed IFN signalling pathways and suggest that this phenotype is mediated via downregulation of interferon regulatory factor binding at gene promoters. Finally, RNA-seq analysis of monocytes of familial hypercholesterolemia (FH) patients also showed type-I IFN suppression which was restored by lipid-lowering therapy and not present in monocytes of healthy donors. Taken together, we define type-I IFN suppression as an athero-protective characteristic of foamy macrophages. These data provide new insights into the mechanisms that control inflammatory responses in hyperlipidaemic settings and can support future therapeutic approaches focusing on reprogramming of macrophages to reduce atherosclerotic plaque progression and improve stability.","abstract":"Macrophages are critical components of atherosclerotic lesions and their pro- and anti-inflammatory responses influence atherogenesis. Type-I interferons (IFNs) are cytokines that play an essential role in antiviral responses and inflammatory activation and have been shown to promote atherosclerosis. Although the impact of type-I IFNs on macrophage foam cell formation is well-documented, the effect of lipid accumulation in monocytes and macrophages on type-I IFN responses remains unknown. Here we examined IFN stimulated (ISG) and non-ISG inflammatory gene expression in mouse and human macrophages that were loaded with acetylated LDL (acLDL), as a model for foam cell formation. We found that acLDL loading in mouse and human macrophages specifically suppressed expression of ISGs and IFN-β secretion, but not other pro-inflammatory genes. The downregulation of ISGs could be rescued by exogenous IFN-β supplementation. Activation of the cholesterol-sensing nuclear liver X receptor (LXR) recapitulated the cholesterol-initiated type-I IFN suppression. Additional analyses of murine in vitro and in vivo generated foam cells confirmed the suppressed IFN signalling pathways and suggest that this phenotype is mediated via downregulation of interferon regulatory factor binding at gene promoters. Finally, RNA-seq analysis of monocytes of familial hypercholesterolemia (FH) patients also showed type-I IFN suppression which was restored by lipid-lowering therapy and not present in monocytes of healthy donors. Taken together, we define type-I IFN suppression as an athero-protective characteristic of foamy macrophages. These data provide new insights into the mechanisms that control inflammatory responses in hyperlipidaemic settings and can support future therapeutic approaches focusing on reprogramming of macrophages to reduce atherosclerotic plaque progression and improve stability.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-20T10:35:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005956","title":"Comprehensive analysis of the clinical, histopathological, radiological and biological features of intra-cranial and extra-cranial BCOR-ITD tumours","description":null,"abstract":"BCOR-ITD tumours form an emerging family of aggressive entities with an internal tandem duplication (ITD) in the last exon of the BCOR gene. The family gathers cerebral localisations, termed High-Grade Neuroepithelial Tumours with BCOR alteration (HGNET-BCOR), and sarcomatous types described in the kidney as Clear-Cell Sarcoma of the Kidney (CCSK), in the endometrium as High-Grade Endometrial Stromal Sarcomas (HG-ESS), in soft tissues as Undifferentiated Round Cell Sarcomas (URCS) or Primitive Myxoid Mesenchymal Tumours of the Infancy (PMMTI), and in bones. Based on a series of 33 retrospective cases, including 10 HGNET-BCOR and 23 BCOR-ITD sarcomas, we interrogated the homogeneity of the entity regarding clinical, radiological, histopathological findings, and molecular signatures. Whole transcriptomic sequencing and DNA methylation profiling were used for unsupervised clustering. \nBCOR-ITD tumours affected mostly young children with a median age at diagnosis of 2.1 years [range 0;62.4]. Median overall survival was 3.9 years and progression-free survival was 1.4 years. This dismal prognosis is shared among all localisations except CCSK cases. Histopathological reviewing revealed marked differences between HGNET-BCOR and BCOR-ITD sarcomas. These two groups were consistently segregated by unsupervised clustering of expression and DNA methylation data. Proximity between the two groups may result from common somatic changes within key pathways directly related to the novel activity of the ITD itself. Conversely, separation in subgroups may result from differences in cells-of-origin","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005957","title":"Oesophageal adenocarcinoma whole exome and RNA-seq raw sequencing data","description":null,"abstract":"Whole exome and RNASeq raw sequencing data for a cohort of 7 male patients with oesophageal adenocarcinoma. Median age at diagnosis was 68. Tumour tissue and PBMCs were used for whole exome sequencing and RNA sequencing.\n\nThis data was generated as part of a study funded by a Cancer Research UK Centres Network Accelerator Award Grant (A21998).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-21T09:49:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005958","title":"The effect of freezing delay of cell-type specific transcriptome responses","description":"We find a similar gene signature is present in post-mortem microglia and astrocytes, across all snRNA-seq datasets analyzed, although it is highly variable between subjects.  Through the use of acutely-resected neurosurgical tissue, we reveal that a similar signature can be detected in microglia following prolonged exposure to room temperature.  These results suggest that the presence of this signature in post-mortem brain samples may be the result of a combination of acute pre-mortem (agonal state, cause of death, comorbidities, etc.) and post-mortem (post-mortem interval (PMI), storage time, RNA quality, etc.) variables.","abstract":"We find a similar gene signature is present in post-mortem microglia and astrocytes, across all snRNA-seq datasets analyzed, although it is highly variable between subjects.  Through the use of acutely-resected neurosurgical tissue, we reveal that a similar signature can be detected in microglia following prolonged exposure to room temperature.  These results suggest that the presence of this signature in post-mortem brain samples may be the result of a combination of acute pre-mortem (agonal state, cause of death, comorbidities, etc.) and post-mortem (post-mortem interval (PMI), storage time, RNA quality, etc.) variables.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005959","title":"EVI1 drives leukemogenesis through aberrant activation of ERG","description":null,"abstract":"Chromosomal rearrangements involving EVI1 (MECOM) define a subtype of acute myeloid leukemia (AML) that is associated with low survival rate. Gene regulatory functions of EVI1 are largely elusive and no targeted therapeutics exist. We developed experimentally tractable murine and human leukemia models that recapitulate phenotypic and transcriptional features of EVI1-rearranged AML and enable large-scale loss-of-function screens. We characterize EVI1-controlled transcriptional programs in cell culture and in vivo, perform CRISPR screens and identify the ETS-related transcription factor ERG as the only gene that is specifically required for EVI1-driven AML. ERG is transcriptionally activated by EVI1 and overexpressed in EVI1-rearranged AML patients. ERG suppression selectively induces terminal differentiation of leukemia cells. EVI1 becomes dispensable for leukemia cells upon ectopic expression of ERG, indicating that key functions of EVI1 are mediated through aberrant activation of ERG. Interfering with this regulatory axis may therefore provide new entry points for rational therapies.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005960","title":"whole exome sequencing of paired tumor-blood samples of squamous cell carcinoma of the bladder","description":null,"abstract":"Pure squamous cell carcinoma (SCC) is the most common pure variant form of bladder cancer, found in 2-5% of cases. It often presents late and is unresponsive to cisplatin-based chemotherapy. The molecular features of these tumours have not been elucidated in detail.  We carried out whole exome sequencing (WES) analysis of bladder SCC, together with copy number and transcriptome data identified molecular signatures in this subtype of bladder cancer. The study includes 11 paired tumour-blood sample sequencing of bladder SCC patients.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005961","title":"Characterisation of stroma of different basal cell carcinoma morphological subtypes","description":null,"abstract":"Basal cell carcinoma (BCC) is the most frequently diagnosed  skin cancer and the most common malignancy in humans. There are different morphological subtypes of BCC that are associated with either low or high risk of recurrence, but the underlying biology of how the individual subtypes arise remains largely unknown.\nBecause it is known that the majority of BCC arise from mutations in the same pathway, we hypothesized that BCC development is also influenced by the tumor microenvironment and in particular by cancer-associated fibroblasts (CAF) and their secreted factors.\nTo get insights on BCC stroma features in the different subtypes, we applied laser-capture microdissection followed by RNA sequencing on a cohort of BCC from 5 different morphological  subtypes.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005962","title":"Mutational_variability_in_oesophagus_in_areas_of_high_SCC_incidence_WGS","description":"We wish to perform whole genome sequencing on 2mm2 areas of histologically normal oeosphageal epithelium to study mutational burden, selection and signatures in samples from areas of high SCC incidence.","abstract":"We wish to perform whole genome sequencing on 2mm2 areas of histologically normal oeosphageal epithelium to study mutational burden, selection and signatures in samples from areas of high SCC incidence.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005963","title":"Ductal keratin 15+ luminal progenitors in normal breast exhibit a basal-like breast cancer transcriptomic signature","description":"Normal breast luminal epithelial progenitors have been implicated as cell of origin in basal-like breast cancer, but their anatomical localization remains understudied. Here, we combine micro-collection of uncultured organoids and single cell mRNA sequencing (scRNA-seq) of FACS-sorted luminal epithelial cells with multicolor imaging to profile ducts and terminal ductal lobular units (TDLUs) and compare them with breast cancer subtypes. Unsupervised clustering reveals eleven distinct clusters and a differentiation trajectory starting with keratin 15+ (K15+) progenitors enriched in ducts. Spatial mapping of luminal progenitors is confirmed at the protein level by staining with critical duct markers. Comparison of the gene expression profiles of normal luminal cells with those of breast cancer subtypes reveals a strong correlation between normal breast K15+ ductal progenitors and basal-like breast cancer. We propose that K15+ basal-like breast cancers originate in ductal progenitors, which emphasizes the importance of not only lineages but also cellular position within the ductal-lobular tree.","abstract":"Normal breast luminal epithelial progenitors have been implicated as cell of origin in basal-like breast cancer, but their anatomical localization remains understudied. Here, we combine micro-collection of uncultured organoids and single cell mRNA sequencing (scRNA-seq) of FACS-sorted luminal epithelial cells with multicolor imaging to profile ducts and terminal ductal lobular units (TDLUs) and compare them with breast cancer subtypes. Unsupervised clustering reveals eleven distinct clusters and a differentiation trajectory starting with keratin 15+ (K15+) progenitors enriched in ducts. Spatial mapping of luminal progenitors is confirmed at the protein level by staining with critical duct markers. Comparison of the gene expression profiles of normal luminal cells with those of breast cancer subtypes reveals a strong correlation between normal breast K15+ ductal progenitors and basal-like breast cancer. We propose that K15+ basal-like breast cancers originate in ductal progenitors, which emphasizes the importance of not only lineages but also cellular position within the ductal-lobular tree.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-25T14:24:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005964","title":"HCA_Kidney_Adult_CZI_RNA","description":"Regional diversity in transcriptional and epigenomic cellular programmes in the human kidney","abstract":"The human kidney is the master regulator of whole organism homeostasis, and achieves a control of acid-base and electrolyte homeostasis along with endocrine regulation of erythropoiesis and blood pressure. Substantial regional variation in cellular populations, activities, and extracellular environments exists in the kidney, including cortico-medullary gradients of osmolality and hypoxia. This study will profile cellular populations through cortico-medullary depth using high throughput joint single-nucleus RNAseq and ATACseq, generating a large scale atlas to probe genomic correlates of regional diversity in the human kidney.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-26T12:00:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005965","title":"TLR7 variants in human lupus patients","description":null,"abstract":"While circumstantial evidence supports enhanced TLR7 signaling as a mechanism of human systemic autoimmune disease, we have lacked the proof afforded by lupus-causing TLR7 gene variants. Here we undertook a whole exome sequencing (WES) approach to identify novel TLR7 variants in human lupus patients. We establish the importance of TLR7 for human SLE pathogenesis, which paves the way for therapeutic TLR7 or MyD88 inhibition.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-26T23:09:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005966","title":"Dual Primary ESCC","description":null,"abstract":"We hypothesize that multicentricity or independent origin rather than multifocality, which means local or lateral spreading involves the development of synchronous ESCC and hypopharyngeal cancer (HPC). Multiple region whole-exome sequencing (M-WES) and clonality analysis were used to assess clonal relationship and spatial inter- or intra-tumor heterogeneity (ITH) in 60 tumor regions from eight dual ESCC/HPC and ten ESCC patients.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005967","title":"Residual ctDNA after treatment predicts early relapse in patients with early-stage non-small cell lung cancer","description":null,"abstract":"Background: Identification of residual disease in patients with localized non-small cell lung cancer (NSCLC) following treatment with curative intent holds promise to identify patients at risk of relapse. New methods can detect circulating tumor DNA (ctDNA) in plasma to fractional concentration of few parts per million, and clinical evidence is required to inform their use.\nPatients and methods: We analyzed 363 serial plasma samples from 88 patients with early-stage NSCLC (48.9%/28.4%/22.7% at stage I/II/III), predominantly adenocarcinomas (62.5%). Patients were treated with curative intent by surgery (N=61), surgery and adjuvant chemotherapy/radiotherapy (N=8), or chemo-radiotherapy (N=19). Tumor exome sequencing identified somatic mutations and plasma was analyzed using patient-specific RaDaR™ assays with up to 48 amplicons targeting tumor-specific variants unique for each patient.\nResults: ctDNA was detected before treatment in 24%, 77% and 87% of stage I, II and III patients respectively, and in 26% of all longitudinal samples. The median tumor fraction detected was 0.042%, with 63% below 0.1% and 36% below 0.01%. ctDNA detection had clinical specificity &gt;98.5% and preceded clinical detection of recurrence of the primary tumor by a median of 212.5 days. ctDNA was detected after treatment with curative intent in 18/28 (64.3%) of patients who had clinical recurrence of their first primary tumor. Detection in the time window 2 weeks-4 months after treatment end was associated with shorter Recurrence Free Survival (RFS; hazard ratio (HR): 14.8, p-value&lt;10-5) and Overall Survival (OS; HR: 5.48, p-value&lt;0.0003). ctDNA was detected 1-3 days after surgery in 25% of patients yet was not associated with disease recurrence. ctDNA detection prior to initial treatment was associated with shorter OS and RFS (HR=2.97 and 3.14, p-values 0.01 and 0.003).\nConclusions: ctDNA detection after initial treatment of patients with early-stage NSCLC using sensitive patient-specific assays has potential to identify patients who may benefit from earlier therapeutic intervention.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005968","title":"Complex genotype-phenotype relationships shape the response to treatment of Down Syndrome Childhood Acute Lymphoblastic Leukaemia","description":null,"abstract":"Extensive genetic and epigenetic variegation has been demonstrated in many malignancies. Importantly, their interplay has the potential to contribute to disease progression and treatment resistance. To shed light on the complex relationships between these different sources of intra-tumour heterogeneity, we explored their relative contributions to the evolutionary dynamics of Acute Lymphoblastic Leukemia (ALL) in children with Down syndrome, which has particularly poor prognosis. We quantified the tumour propagating potential of genetically distinct sub-clones using serial transplantation assays and SNP-arrays. While most leukaemias were characterized by a single dominant subclone, others were highly heterogeneous. Importantly, we provide clear and direct evidence that genotypes and phenotypes with functional relevance to leukemic progression and treatment resistance can co-segregate within the disease. Hence, individual genetic lesions can be restricted to well-defined cell immunophenotypes, corresponding to different stages of the leukemic differentiation hierarchy and varied proliferation potentials. As a result of this difference in fitness, which can be accurately quantified via competitive transplantation assays, matching diagnostic, post-treatment, and relapse leukemias can be dominated by different genotypes, including pre-leukemic clones persisting throughout the disease progression and treatment. Intriguingly, plasticity also appears to be a temporally defined property that can segregate with genotype. These results suggest that Down Syndrome ALL should be viewed as a complex matrix of cells exhibiting genetic and epigenetic heterogeneity that foster extensive clonal evolution and competition. Therapeutic intervention reshapes this ‘eco-system’ and may provide the right conditions for the preferential expansion of selected compartments and subsequently relapse.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005969","title":"LifeLines-NEXT pilot study","description":"The pilot study from the LifeLines-NEXT (NEXT) cohort consisting of 30 mother-infant pairs with longitudinal sampling from pregnancy till 3 months after birth. Shotgun data is available for virome and microbiome annotation.","abstract":"The pilot study from the LifeLines-NEXT (NEXT) cohort consisting of 30 mother-infant pairs with longitudinal sampling from pregnancy till 3 months after birth. Shotgun data is available for virome and microbiome annotation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-28T08:27:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005970","title":"Genome analysis of early onset sporadic rectal cancer","description":null,"abstract":"Early-onset sporadic rectal cancer (EOSRC) is a unique and predominant colorectal cancer\n(CRC) subtype in India. To identify molecular alterations underlying rectal adenocarcinoma, we performed whole-exome sequencing analysis of 47 carefully selected well-annotated microsatellite stable (MSS) rectal tumor and matched normal sample pairs (EOSRC-IN).","study_type":"Cancer Genomics","pubmed_ids":[33262464],"external_links":null,"is_released":true,"released_date":"2022-01-28T10:25:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005971","title":"Evaluating the immune response in treatment-naive hospitalised patients with influenza and COVID-19","description":"Clinical characteristics and peripheral blood were acquired upon hospital admission from two well characterised cohorts, a cohort of patients infected with influenza and a cohort of patients infected with SARS-CoV-2 during the first wave of the pandemic and prior to availability of COVID-19 treatments and vaccines.","abstract":"Clinical characteristics and peripheral blood were acquired upon hospital admission from two well characterised cohorts, a cohort of patients infected with influenza and a cohort of patients infected with SARS-CoV-2 during the first wave of the pandemic and prior to availability of COVID-19 treatments and vaccines.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-28T11:37:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005972","title":"H3Africa - Consortium WGS","description":"To address gaps in sequence data for some of the African populations being studied in H3Africa projects, additional sequencing has been carried out through various projects and the data are being made available. The first dataset includes a high coverage whole genome sequence dataset  generated at the Baylor College of Medicine with samples provided by H3Africa PIs and collaborators, funded by the National Institutes of Health.  The sequence data files are accompanied by minimal metadata, including country, ethnic group (where available) and sex.","abstract":"To address gaps in sequence data for some of the African populations being studied in H3Africa projects, additional sequencing has been carried out through various projects and the data are being made available. The first dataset includes a high coverage whole genome sequence dataset  generated at the Baylor College of Medicine with samples provided by H3Africa PIs and collaborators, funded by the National Institutes of Health.  The sequence data files are accompanied by minimal metadata, including country, ethnic group (where available) and sex.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-28T12:34:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005973","title":"ENCORAFENIB COMBINED WITH BINIMETINIB FOR BRAFV600E-MUTATED RELAPSED/REFRACTORY MULTIPLE MYELOMA: THE PHASE II GMMG-BIRMA TRIAL (Hipo_K08K)","description":"Activating BRAF mutations are rare events in multiple myeloma but have been shown to be promising therapeutic targets in small case studies. This multicenter phase II trial assessed the efficacy and safety of the BRAF/MEK inhibitors, encorafenib and binimetinib, in patients with relapsed/refractory multiple myeloma (RRMM) carrying an activating BRAFV600E mutation.\nTwelve RRMM patients with a median of five prior lines of therapy were enrolled. The study met its primary endpoint with 10 patients achieving at least a partial response according to IMWG criteria (overall response rate 83.3%). Responses occurred rapidly within the first cycle and deepened over time. The median progression-free survival (PFS) was 5.6 months and overall survival was 55% at 24 months.\nGenomic profiling revealed RAS mutations and structural variants involving the BRAF locus to be drivers of resistance to BRAF/MEK inhibition in RRMM. This trial demonstrates the value of translationally driven clinical trials in selected patient populations.","abstract":"Activating BRAF mutations are rare events in multiple myeloma but have been shown to be promising therapeutic targets in small case studies. This multicenter phase II trial assessed the efficacy and safety of the BRAF/MEK inhibitors, encorafenib and binimetinib, in patients with relapsed/refractory multiple myeloma (RRMM) carrying an activating BRAFV600E mutation.\nTwelve RRMM patients with a median of five prior lines of therapy were enrolled. The study met its primary endpoint with 10 patients achieving at least a partial response according to IMWG criteria (overall response rate 83.3%). Responses occurred rapidly within the first cycle and deepened over time. The median progression-free survival (PFS) was 5.6 months and overall survival was 55% at 24 months.\nGenomic profiling revealed RAS mutations and structural variants involving the BRAF locus to be drivers of resistance to BRAF/MEK inhibition in RRMM. This trial demonstrates the value of translationally driven clinical trials in selected patient populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-28T13:29:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005974","title":"An Isogenic Cell Line Panel for Sequence-based Screening of Targeted Anti-cancer Drugs","description":"We describe the creation and characterization of an isogenic cell line panel representing common cancer pathways, with multiple features optimized for high-throughput screening. More than 1,800 cell lines from three normal human cells were generated using CRISPR-technologies. Surprisingly, we discovered most of these lines did not result in complete gene inactivation, despite integration of sgRNA at the desired genomic site. However, a subset of the lines harbored true, biallelic disruptions of the targeted tumor suppressor gene, yielding a final panel of 100 well-characterize lines covering 19 pathways frequently subject to loss of function in cancers. This panel included genetic markers optimized for sequence-based ratiometric assays for drug-based screening assays. To illustrate the potential utility of this panel, we developed a multiplexed high-throughput screen that identified Wee1 inhibitor MK-1775 as a selective growth inhibitor of cells with inactivation of TP53. These cell lines and screening approach should prove useful for researchers studying a variety of cellular and biochemical phenomena","abstract":"We describe the creation and characterization of an isogenic cell line panel representing common cancer pathways, with multiple features optimized for high-throughput screening. More than 1,800 cell lines from three normal human cells were generated using CRISPR-technologies. Surprisingly, we discovered most of these lines did not result in complete gene inactivation, despite integration of sgRNA at the desired genomic site. However, a subset of the lines harbored true, biallelic disruptions of the targeted tumor suppressor gene, yielding a final panel of 100 well-characterize lines covering 19 pathways frequently subject to loss of function in cancers. This panel included genetic markers optimized for sequence-based ratiometric assays for drug-based screening assays. To illustrate the potential utility of this panel, we developed a multiplexed high-throughput screen that identified Wee1 inhibitor MK-1775 as a selective growth inhibitor of cells with inactivation of TP53. These cell lines and screening approach should prove useful for researchers studying a variety of cellular and biochemical phenomena","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-28T16:26:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005975","title":"850k Methyome analysis of snap frozen or FFPE stored human MBM","description":"We performed a 850k infinium bead chip-based global methylome analysis of MBM.","abstract":"We performed a 850k infinium bead chip-based global methylome analysis of MBM.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-29T20:18:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005976","title":"Molecular programs of melanoma brain metastases (MBM)","description":"We performed paired-end whole transcriptome sequencing of fresh frozen or intraoperative brain metastases of therapeutically treated stage IV melanoma patients. In addition, we analysed the epigenetic landscape of tumors usind Illumina 850k bead chip technology.","abstract":"We performed paired-end whole transcriptome sequencing of fresh frozen or intraoperative brain metastases of therapeutically treated stage IV melanoma patients. In addition, we analysed the epigenetic landscape of tumors usind Illumina 850k bead chip technology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-29T20:18:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005977","title":"Stubberfield familial aortopathy","description":null,"abstract":"Use linkage analysis to find causative variant for familial aortic dissection. Best candidate is DVL2.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005978","title":"Bulk RNA sequencing of Singapore colorectal cancer patients (SG-BULK)","description":"The study was approved by the institutional review board of Singhealth (2018-2795). Ten 5-µm tissue sections were cut using standard microtomy techniques. Each collected cell population was then extracted using the allprep kit. Extracted material was then quantified using a Qubit fluorometer.","abstract":"The study was approved by the institutional review board of Singhealth (2018-2795). Ten 5-µm tissue sections were cut using standard microtomy techniques. Each collected cell population was then extracted using the allprep kit. Extracted material was then quantified using a Qubit fluorometer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-31T04:13:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005979","title":"Raw multi-omics dataset from the lungNENomics cohort of lung neuroendocrine tumours","description":"This study contains raw multi-omics data generated as part of the lungNENomics project, a multi-omics study aimed at deep molecular profiling of lung neuroendocrine tumours, including typical carcinoids (grade 1) and atypical carcinoids (grade 2). The study includes whole-genome sequencing (WGS), RNA sequencing (RNA-seq), and Infinium MethylationEPIC array data from samples in the lungNENomics cohort. These raw data complement the associated processed molecular data released on Zenodo (10.5281/zenodo.19366762) and the corresponding whole-slide pathology images deposited in the EBI BioImage Archive (10.6019/S-BIAD3143). See Sexton-Oates et al medrxiv 2025 (https://www.medrxiv.org/content/10.1101/2025.07.18.25331556v1) for details.","abstract":"This study contains raw multi-omics data generated as part of the lungNENomics project, a multi-omics study aimed at deep molecular profiling of lung neuroendocrine tumours, including typical carcinoids (grade 1) and atypical carcinoids (grade 2). The study includes whole-genome sequencing (WGS), RNA sequencing (RNA-seq), and Infinium MethylationEPIC array data from samples in the lungNENomics cohort. These raw data complement the associated processed molecular data released on Zenodo (10.5281/zenodo.19366762) and the corresponding whole-slide pathology images deposited in the EBI BioImage Archive (10.6019/S-BIAD3143). See Sexton-Oates et al medrxiv 2025 (https://www.medrxiv.org/content/10.1101/2025.07.18.25331556v1) for details.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-31T08:39:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005980","title":"Unravelling the contribution of HIF pathway and its therapeutic potential in human AML leukemia-initiating cells","description":"This study hypothesized that hypoxia contributes to AML-LSCs function and represents a potential therapeutic target to sensitize AML-LSCs to chemotherapy. We provide a comprehensive single-cell expression atlas of AML patient-matched diagnostic-relapsed samples from risk-stratified human AML patients.","abstract":"This study hypothesized that hypoxia contributes to AML-LSCs function and represents a potential therapeutic target to sensitize AML-LSCs to chemotherapy. We provide a comprehensive single-cell expression atlas of AML patient-matched diagnostic-relapsed samples from risk-stratified human AML patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-31T10:57:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005981","title":"Longitudinal profiling of circulating tumour DNA for tracking tumour dynamics in pancreatic cancer","description":"The utility of circulating tumour DNA (ctDNA) for longitudinal tumour monitoring in pancreatic ductal adenocarcinoma (PDAC) has not been explored beyond mutations in the KRAS proto-oncogene. We aim to characterise and track patient-specific somatic ctDNA variants, to assess longitudinal changes in disease burden and explore the landscape of actionable alterations.","abstract":"The utility of circulating tumour DNA (ctDNA) for longitudinal tumour monitoring in pancreatic ductal adenocarcinoma (PDAC) has not been explored beyond mutations in the KRAS proto-oncogene. We aim to characterise and track patient-specific somatic ctDNA variants, to assess longitudinal changes in disease burden and explore the landscape of actionable alterations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-31T12:31:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005982","title":"Germline TP53 mutations undergo copy number gain years prior to tumor diagnosis","description":"Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome associated with germline TP53 mutations. We performed whole-genome sequence (WGS) analysis of tumors from 22 TP53 mutation carriers. We observed somatic mutations affecting Wnt, PI3K/AKT signaling, epigenetic modifiers and homologous recombination genes as well as mutational signatures associated with prior chemotherapy. We identified near-ubiquitous early loss of heterozygosity of TP53, with gain of the mutant allele. This occurred earlier in these tumors compared to tumors with somatic TP53 mutations, suggesting the timing of this mark may distinguish germline from somatic TP53 mutations. Phylogenetic trees of tumor evolution, reconstructed from bulk and multi-region WGS, revealed that LFS tumors exhibit comparatively limited heterogeneity. Overall, our study delineates early copy number gains of mutant TP53 as a characteristic mutational process in LFS tumorigenesis, likely arising very early in life or in utero.years prior to tumor diagnosis.","abstract":"Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome associated with germline TP53 mutations. We performed whole-genome sequence (WGS) analysis of tumors from 22 TP53 mutation carriers. We observed somatic mutations affecting Wnt, PI3K/AKT signaling, epigenetic modifiers and homologous recombination genes as well as mutational signatures associated with prior chemotherapy. We identified near-ubiquitous early loss of heterozygosity of TP53, with gain of the mutant allele. This occurred earlier in these tumors compared to tumors with somatic TP53 mutations, suggesting the timing of this mark may distinguish germline from somatic TP53 mutations. Phylogenetic trees of tumor evolution, reconstructed from bulk and multi-region WGS, revealed that LFS tumors exhibit comparatively limited heterogeneity. Overall, our study delineates early copy number gains of mutant TP53 as a characteristic mutational process in LFS tumorigenesis, likely arising very early in life or in utero.years prior to tumor diagnosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-31T21:58:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005983","title":"Epithelioid sarcoma sequencing data","description":"This study shares DNA and RNA sequencing data from Epithelioid sarcoma patients","abstract":"This study shares DNA and RNA sequencing data from Epithelioid sarcoma patients","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-01-31T23:01:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005984","title":"The genomic and immune landscape of long-term survivors of high-grade serous ovarian cancer","description":"Less than half of all patients with advanced-stage high-grade serous ovarian cancers (HGSC) survive more than five years post-diagnosis but those who have an exceptionally long survival could provide insights into tumor biology and therapeutic approaches. We analyzed 60 patients with advanced-stage, HGSC who survived more than 10 years after diagnosis using whole-genome sequencing, transcriptome, and methylome profiling of their primary tumor samples, comparing this data to 66 short- or moderate-term survivors. Tumors of long-term survivors were more likely to have multiple alterations in genes associated with DNA repair, and more frequent somatic variants resulting in an increased predicted neoantigen load. Patients clustered into survival groups based on genomic and immune cell signatures, including three subsets of patients with BRCA1 alterations with distinctly different outcomes. Specific combinations of germline and somatic gene alterations, tumor cell phenotypes, and differential immune responses appear to contribute to long-term survival in HGSC.","abstract":"Less than half of all patients with advanced-stage high-grade serous ovarian cancers (HGSC) survive more than five years post-diagnosis but those who have an exceptionally long survival could provide insights into tumor biology and therapeutic approaches. We analyzed 60 patients with advanced-stage, HGSC who survived more than 10 years after diagnosis using whole-genome sequencing, transcriptome, and methylome profiling of their primary tumor samples, comparing this data to 66 short- or moderate-term survivors. Tumors of long-term survivors were more likely to have multiple alterations in genes associated with DNA repair, and more frequent somatic variants resulting in an increased predicted neoantigen load. Patients clustered into survival groups based on genomic and immune cell signatures, including three subsets of patients with BRCA1 alterations with distinctly different outcomes. Specific combinations of germline and somatic gene alterations, tumor cell phenotypes, and differential immune responses appear to contribute to long-term survival in HGSC.","study_type":"Other","pubmed_ids":[36456881],"external_links":null,"is_released":true,"released_date":"2022-02-01T07:50:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005985","title":"The polarity and specificity of antiviral T lymphocyte responses determine susceptibility to SARS-CoV-2 infection in cancer patients and healthy individuals.","description":"The goal of this study was to identify immune correlates of clinical protection against SARS-CoV-2 infection.","abstract":"The goal of this study was to identify immune correlates of clinical protection against SARS-CoV-2 infection.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-01T11:07:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005986","title":"Biallelic HMBS Inactivation Defines a Homogenous Clinico-Molecular Subtype of Hepatocellular Carcinoma","description":"Acute intermittent porphyria (AIP), caused by heterozygous germline mutations of the heme synthesis pathway enzyme HMBS (hydroxymethylbilane synthase), confers high risk of hepatocellular carcinoma (HCC) development. Yet, the role of HMBS in liver tumorigenesis remains unclear. Here we explore HMBS alterations in a large series of 758 HCC. We identify recurrent bi-allelic HMBS inactivation, both in AIP patients acquiring a second somatic HMBS mutation and in sporadic HCC with two somatic hits. HMBS alterations are enriched in truncative mutations, in particular in splice regions, leading to abnormal transcript structures. Bi-allelic HMBS inactivation results in a massive accumulation of its toxic substrate porphobilinogen and synergizes with CTNNB1 activating mutations, leading to the development of well differentiated tumors with a transcriptomic signature of Wnt/ß-catenin pathway activation and a DNA methylation signature related to ageing. HMBS-inactivated HCC mostly affect females, in absence of fibrosis and classical HCC risk factors. These data identify HMBS as a tumor suppressor gene whose bi-allelic inactivation defines a homogenous clinical and molecular HCC subtype.","abstract":"Acute intermittent porphyria (AIP), caused by heterozygous germline mutations of the heme synthesis pathway enzyme HMBS (hydroxymethylbilane synthase), confers high risk of hepatocellular carcinoma (HCC) development. Yet, the role of HMBS in liver tumorigenesis remains unclear. Here we explore HMBS alterations in a large series of 758 HCC. We identify recurrent bi-allelic HMBS inactivation, both in AIP patients acquiring a second somatic HMBS mutation and in sporadic HCC with two somatic hits. HMBS alterations are enriched in truncative mutations, in particular in splice regions, leading to abnormal transcript structures. Bi-allelic HMBS inactivation results in a massive accumulation of its toxic substrate porphobilinogen and synergizes with CTNNB1 activating mutations, leading to the development of well differentiated tumors with a transcriptomic signature of Wnt/ß-catenin pathway activation and a DNA methylation signature related to ageing. HMBS-inactivated HCC mostly affect females, in absence of fibrosis and classical HCC risk factors. These data identify HMBS as a tumor suppressor gene whose bi-allelic inactivation defines a homogenous clinical and molecular HCC subtype.","study_type":"Other","pubmed_ids":[35636578],"external_links":null,"is_released":true,"released_date":"2022-02-01T20:33:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005987","title":"Targeted_NanoSeq_from_non_invasive_lung_samples","description":"Targeted NanoSeq in non-invasive samples from individuals with smoking-background and high-risk for lung cancer. A custom-designed panel of ~400 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites). The driver landscape across different types of non-invasive sampling strategies will be compared to each other.","abstract":"Investigating the driver landscape across individuals at high-risk for developing lung cancer utilizing buccal swabs, nasal swabs as well as bronchial brushings and lavages with the aim to create prognostic value for cancer risk prediction.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005988","title":"Spatial_transcriptomic_profiling_of_pre_malignant_and_malignant_lung_tissue_VISIUM","description":"Recently, a study of human bronchial epithelium has demonstrated the abudance of cellular populations with low near-normal mutation burden in individuals with heavy smoking history. The origin and mechanism behind this observation, where cells presumably avoid the effect of tobacco and the accompanying somatic mutaitons remains unknown. We hypothesized that the occurrence of these cells is due to a protected stem cell niche in submucosal glands and ducts, which get reactivated upon smoking cessation. To demonstrate this, and to investigate the transcriptome of specific spatial locations, we will utilise 10X VISIUM spatial transcriptomics in order to analyse the gene expression landscape of submucosal glands, ducts as well as bronchial epithelium in ex-smokers. More importantly, we will aim at combining this approach with matched genomic data generated using laser-capture microdissection of adjacent tissue section. Ultimately, this will enable us to infer genotype to phenotype associations in clonal populations with distinct mutation burden.","abstract":"This study will aim to characterize the downstream effects of high and low somatic mutation burden in lung tissue from patients with smoking history. The data in this study will be generated by spatial transcriptomic profiling of fresh frozen and paxgene-fixed tissue using 10x Genomics VISIUM assay. The spatial gene expression data will be then matched to genomic data from adjacent tissue sections to infer genotype-phenotype associations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005989","title":"Targeted_nanoseq_paediatric_autopsy","description":"Targeted NanoSeq across a range of tissues taken at autopsy from patients with lethal paediatric brain tumours using a custom-designed panel of ~200 genes to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape in the background normal tissues of patients with brain tumours.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005990","title":"Bulk_sequencing_study_for_human_male_germline","description":"This study aims to understand the gene expression changes in male reproductive tissues during spermatogenesis using integrated multi-omics analysis. Different populations from testis biopsies, including spermatogonia stem cells, primary spermatocytes, secondary spermatocytes, spermatids and mature sperms, were sorted based on the DNA content. In addition to the G&amp;T sequencing results for single cells, we sorted bulk samples for those populations for Nanoseq to detect the mutations at low error rate.","abstract":"During an individual's lifetime, human cells accumulate mutations which contribute to the development of cancer, ageing and other diseases. Mutations can be caused by genetic and environmental factors and are classified as germline and somatic mutations. While the former are the source of inherited diseases and evolunationary adaptions, the later are not passed from parents to their offspring. \n\nThe mutation burden and patterns are different between tissue types, but the mutation rates are consistant within tissue type. A recent study has shown that germline cells have a considerably lower mutation rate compared to their somatic counterparts. However, how this low mutation burden is achieved by the germline cells remain elusive. This study aims to investigate how factors such as gene expression and DNA repairation may protect the germline cells from accuring mutations during the natural process of ageing compared to the soma. \n\nRapid technological development in sequencing approaches provide insights into gene expression changes in human cells. Particularly, single- cell RNA-seq can measure the gene expression levels for each transcript within each individual cell. Moreover, we will use Nanoseq which has the error rate of less than five per billion base pairs for bulk samples to detect mutations in single, terminally differentiated cells.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-03T09:48:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005991","title":"Bulk_sequencing_study_for_human_male_germline_RNA","description":"This study aims to understand the gene expression changes in male reproductive tissues during spermatogenesis using integrated multi-omics analysis. Different populations from testis biopsies, including spermatogonia stem cells, primary spermatocytes, secondary spermatocytes, spermatids and mature sperms, were sorted based on the DNA content. In addition to the G&amp;T sequencing results for single cells, we sorted bulk samples for those populations for Nanoseq to detect the mutations at low error rate.","abstract":"During an individual's lifetime, human cells accumulate mutations which contribute to the development of cancer, ageing and other diseases. Mutations can be caused by genetic and environmental factors and are classified as germline and somatic mutations. While the former are the source of inherited diseases and evolunationary adaptions, the later are not passed from parents to their offspring. \n\nThe mutation burden and patterns are different between tissue types, but the mutation rates are consistant within tissue type. A recent study has shown that germline cells have a considerably lower mutation rate compared to their somatic counterparts. However, how this low mutation burden is achieved by the germline cells remain elusive. This study aims to investigate how factors such as gene expression and DNA repairation may protect the germline cells from accuring mutations during the natural process of ageing compared to the soma. \n\nRapid technological development in sequencing approaches provide insights into gene expression changes in human cells. Particularly, single- cell RNA-seq can measure the gene expression levels for each transcript within each individual cell. Moreover, we will use Nanoseq which has the error rate of less than five per billion base pairs for bulk samples to detect mutations in single, terminally differentiated cells.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005992","title":"Cell-free DNA and bone marrow samples from myelodysplastic syndromes","description":"We have assessed the molecular profile of a cohort of 70 patients with MDS by next-generation sequencing (NGS) using cfDNA and compared the results to paired bone marrow (BM) DNA. Sequencing of BM DNA and cfDNA showed a comparable mutational profile and variant allele frequencies (VAF) strongly correlated between both sample types. Our results support the analysis of cfDNA as a promising strategy for performing molecular characterization, detection of chromosomal aberrations and monitoring of MDS patients.","abstract":"We have assessed the molecular profile of a cohort of 70 patients with MDS by next-generation sequencing (NGS) using cfDNA and compared the results to paired bone marrow (BM) DNA. Sequencing of BM DNA and cfDNA showed a comparable mutational profile and variant allele frequencies (VAF) strongly correlated between both sample types. Our results support the analysis of cfDNA as a promising strategy for performing molecular characterization, detection of chromosomal aberrations and monitoring of MDS patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-03T10:34:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005993","title":"Host genotyping data from Dutch adult bacterial meningitis patients and linked bacterial genome sequences","description":"Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown.\n\nThis study includes 1146 samples of host genotyping data (genotyped and imputed) from Illumina Omni arrays. Samples were collected from adults (&gt;16 yrs) patients with CSF confirmed bacterial meningitis in the Netherlands between 2006 and 2015. Metadata includes patient outcome, species of bacteria, and for 467 samples a link to an ENA run with the associated bacterial genome (S. pneumoniae only).","abstract":"Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown.\n\nThis study includes 1146 samples of host genotyping data (genotyped and imputed) from Illumina Omni arrays. Samples were collected from adults (&gt;16 yrs) patients with CSF confirmed bacterial meningitis in the Netherlands between 2006 and 2015. Metadata includes patient outcome, species of bacteria, and for 467 samples a link to an ENA run with the associated bacterial genome (S. pneumoniae only).","study_type":"Other","pubmed_ids":[31092817],"external_links":null,"is_released":true,"released_date":"2022-02-03T11:07:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005994","title":"DERMATLAS__Cutaneous_squamous_cell_carcinoma_WES","description":"Cutaneous squamous cell carcinoma (cSCC) is one of the commonest malignancies in the western world with incident rates increasing year on year. cSCC represents a massive health and economic burden yet despite this there is a paucity of efficacious treatment options available for advanced disease. Chronic ultraviolet radiation exposure of the skin results in DNA damage that underpins the transformation of keratinocytes or their progenitors. This can result in the growth of cell clones in the skin followed by the development of pre-malignant Actinic Keratoses (AK), primary cSCC and ultimately potentially lethal metastatic disease. Despite being one of the most frequent human cancers, cSCC is one of the least studied in terms of molecular pathogenesis. Limited molecular profiling studies so far have revealed that cSCCs harbour complex genomes containing numerous rearrangements and up thousands of mutations but genetic events that drive disease progression to metastasis remain to be established. Here we investigate the genetic landscape of primary tumours that fail to metastasise, those that have metastasised and their matched metastatic lesions using anonymised routine formalin fixed paraffin embedded samples.","abstract":"Cutaneous squamous cell carcinoma (cSCC) is one of the commonest malignancies in the western world with incident rates increasing year on year. cSCC represents a massive health and economic burden yet despite this there is a paucity of efficacious treatment options available for advanced disease. Chronic ultraviolet radiation exposure of the skin results in DNA damage that underpins the transformation of keratinocytes or their progenitors. This can result in the growth of cell clones in the skin followed by the development of pre-malignant Actinic Keratoses (AK), primary cSCC and ultimately potentially lethal metastatic disease. Despite being one of the most frequent human cancers, cSCC is one of the least studied in terms of molecular pathogenesis. Limited molecular profiling studies so far have revealed that cSCCs harbour complex genomes containing numerous rearrangements and up thousands of mutations but genetic events that drive disease progression to metastasis remain to be established. Here we investigate the genetic landscape of primary tumours that fail to metastasise, those that have metastasised and their matched metastatic lesions using anonymised routine formalin fixed paraffin embedded samples.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005995","title":"To determine the genomic profile of Triple Negative Breast Cancer patient-derived xenografts (PDX cohort)","description":"Specific BRCA and immune configurations determine optimal response to platinum-based chemotherapy in triple negative breast and ovarian carcinomas (PDX_WGS)","abstract":"Specific BRCA and immune configurations determine optimal response to platinum-based chemotherapy in triple negative breast and ovarian carcinomas (PDX_WGS)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-03T20:00:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005996","title":"B-cell Lymphoma multi-regional tumor tissue profiling through a RAP study","description":null,"abstract":"Intratumoral heterogeneity (ITH) provides the substrate for tumor evolution and treatment resistance, yet is remarkably understudied in lymphoma. Furthermore, the trajectory of how lymphoma spreads throughout the human body remains poorly understood. Here, we present a detailed characterization of ITH by applying whole genome sequencing to spatially separated tumor samples harvested at the time of autopsy and/or diagnosis in three patients presenting with refractory B-cell non-Hodgkin lymphoma. Through deconvolution of bulk samples into clonal mixtures and inference of phylogenetic trees, we found evidence that polyclonal seeding underlies tumor dissemination in lymphoma and identified mutation signatures associated with ancestral and descendant clones. In our series of patients with highly refractory lymphoma, the determinants of resistance were often harbored by founding clones, although there was also evidence of positive selection of driver mutations, likely under the influence of therapy. Lastly, we show that ctDNA is suitable for the detection of ancestral mutations but may miss a significant proportion of private mutations that can be detected in tissue. Our study clearly shows the existence of intricate patterns of regional and anatomical evolution that can only be disentangled through multi-regional tumor tissue profiling.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005997","title":"Bioinformatics analysis of chimerism in monochorionic dizygotic twins","description":"We conducted a bioinformatics analysis of hematopoietic chimerism of the monochorionic dizygotic twins. Whole-genome sequencing was used to understand the genomic compositions of the chimeras.","abstract":"We conducted a bioinformatics analysis of hematopoietic chimerism of the monochorionic dizygotic twins. Whole-genome sequencing was used to understand the genomic compositions of the chimeras.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-04T01:57:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001005998","title":"Tracing the timing of twinning using somatic mutations","description":"We sequenced the whole-genome sequences of monozygotic twins and their parents to retrospectively trace the timing of twinning. Placenta and umbilical cord were also used to draw the relative relationship between the embryo proper and the extraembryonic tissue.","abstract":"We sequenced the whole-genome sequences of monozygotic twins and their parents to retrospectively trace the timing of twinning. Placenta and umbilical cord were also used to draw the relative relationship between the embryo proper and the extraembryonic tissue.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001005999","title":"HCA_Female_Reproductive_Paediatric_CZI_RNA","description":"HCA Female Reproductive Paediatric CZI RNA Managed Access","abstract":"This project proposes to profile cortex from children ovaries from a unique tissue acquisition resource: a biobank of cryopreserved tissue of the ovarian cortex from children undergoing cancer treatment. Samples are collected prior to cancer treatment and cryopreserved for future fertility treatments, and research using single-cell transcriptomics (scRNA-seq) and single-cell chromatin accessibility methods (scATAC-seq) will be used to profile pre- and postpubertal ovaries.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006000","title":"Transcriptome_analysis_of_PBMC_in_the_UKB_cohort","description":"This data set contains 10x genomics single cell 3' transcriptome profiling of PBMC from the blood donors participating in the UK Biobank (UKB) study. Each individually tagged library contains 20,000 individual PBMC sourced from 10-13 individual donors that require deconvolution of to be analysed separately.","abstract":"The Cardinal project is a large scale single cell transcriptomics project analysing human PBMC's. The main aim of the study is to generate a reference data set of gene expression measurements in human immune cells that could be used in quantitative trait loci analysis (QTL). The study will be constructed from several thousand donors from both UK British and South Asia populations enabling the association of rare variants and non-European alleles with changes in gene expression levels in specific cell types. Participants within the study have been extensively phenotyped with genome wide association data sets being generated or available. Enabling the integration of genetic associated changes in gene expression with GWAS for traits and disease. This data set contains 10x genomics single cell 3' transcriptome profiling of PBMC from the blood donors (n=~5000) participating in the UK Biobank (UKB) study. Each individually tagged library contains 20,000 individual PBMC sourced from 10-13 individual donors that require deconvolution of to be analysed separately.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006001","title":"Combination of ribociclib and gemcitabine for the treatment of medulloblastoma","description":"Group 3 (G3) medulloblastoma (MB) is one of the deadliest forms of the disease for which novel treatment is desperately needed. Here we evaluate ribociclib, a highly selective CDK4/6 inhibitor, with gemcitabine in mouse and human G3 MBs. Ribociclib CNS penetration was assessed by in vivo microdialysis and by immunohistochemistry and gene expression studies. Survival studies to determine the efficacy of ribociclib and gemcitabine combination were performed on mice orthotopically implanted with luciferase labelled mouse and human G3 MB. Pharmacokinetic-pharmacodynamic outcomes and univariable survival models were analyzed to estimate survival. Gene activity inference using NetBID and tumor differentiation analysis investigated the effects of the combination after short and long-term treatments. Tumors from mice treated with oral ribociclib displayed inhibited RB phosphorylation, downregulated E2F target genes, and decreased proliferation. Treatment of mice with the combination of ribociclib and gemcitabine was well tolerated, slowed tumor progression and metastatic spread, and increased survival. Molecular analysis of treated versus untreated tumors showed a significant decrease in the activity and expression of genes involved in cell cycle progression and DNA damage response, and an increase in activity and expression of genes implicated in neuronal identity and neuronal differentiation.  Ribociclib is CNS-penetrant. When administered/combined with gemcitabine in orthotopic G3 MB models resulted in improved survival. Our findings, with both mouse and human patient-derived-orthotopic xenograft models, suggest that this combination therapy has promise for children with G3 MB and may represent an effective treatment strategy for other CNS malignancies.","abstract":"Group 3 (G3) medulloblastoma (MB) is one of the deadliest forms of the disease for which novel treatment is desperately needed. Here we evaluate ribociclib, a highly selective CDK4/6 inhibitor, with gemcitabine in mouse and human G3 MBs. Ribociclib CNS penetration was assessed by in vivo microdialysis and by immunohistochemistry and gene expression studies. Survival studies to determine the efficacy of ribociclib and gemcitabine combination were performed on mice orthotopically implanted with luciferase labelled mouse and human G3 MB. Pharmacokinetic-pharmacodynamic outcomes and univariable survival models were analyzed to estimate survival. Gene activity inference using NetBID and tumor differentiation analysis investigated the effects of the combination after short and long-term treatments. Tumors from mice treated with oral ribociclib displayed inhibited RB phosphorylation, downregulated E2F target genes, and decreased proliferation. Treatment of mice with the combination of ribociclib and gemcitabine was well tolerated, slowed tumor progression and metastatic spread, and increased survival. Molecular analysis of treated versus untreated tumors showed a significant decrease in the activity and expression of genes involved in cell cycle progression and DNA damage response, and an increase in activity and expression of genes implicated in neuronal identity and neuronal differentiation.  Ribociclib is CNS-penetrant. When administered/combined with gemcitabine in orthotopic G3 MB models resulted in improved survival. Our findings, with both mouse and human patient-derived-orthotopic xenograft models, suggest that this combination therapy has promise for children with G3 MB and may represent an effective treatment strategy for other CNS malignancies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-04T16:54:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006002","title":"Specific BRCA and immune configurations determine optimal response to platinum-based chemotherapy in triple negative breast and ovarian carcinomas (COH_TNBC_RNAseq)","description":"To determine the trascriptional profiles of Triple Negative Breast Cancers (COH cohort)","abstract":"To determine the trascriptional profiles of Triple Negative Breast Cancers (COH cohort)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-04T18:46:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006003","title":"Bioinformatic analysis of monochorionic dizygotic twins","description":null,"abstract":"We conducted a bioinformatics analysis of hematopoietic chimerism of the monochorionic dizygotic twins. Whole-genome sequencing and single cell sequencing was used to understand the genomic compositions of the chimeras.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006004","title":"Multimodal immunogenomic biomarker analysis of tumors from pediatric patients enrolled to a phase 1-2 study of single-agent atezolizumab","description":"We report herein an extensive exploratory biomarker analysis of refractory tumors taken from pediatric patients prior to receiving atezolizumab monotherapy in the phase 1-2 iMATRIX-atezolizumab trial (NCT02541604). A high percentage of CD8+ T cells and elevated protein levels of programmed cell death ligand 1 (PD-L1) were associated with progression-free survival (PFS). T-cell receptor (TCR) sequencing revealed that diverse infiltrating TCR repertoire at baseline was prognostic. We found no associations between panel-based tumor mutation burden (TMB) or specific genetic aberrations with PFS in this study. Through a pan-cancer gene co-expression network analysis, we developed a novel tumor-agnostic Pediatric Cytotoxicity and Antigen Presentation (PedCAP) signature that was associated with improved PFS in the iMATRIX-atezo study. Our study highlights features of immune response in pediatric cancers when treated with immune checkpoint inhibitors and provides a multi-biomarker pediatric immunogram framework to guide prospective clinical trials in pediatric cancers.","abstract":"We report herein an extensive exploratory biomarker analysis of refractory tumors taken from pediatric patients prior to receiving atezolizumab monotherapy in the phase 1-2 iMATRIX-atezolizumab trial (NCT02541604). A high percentage of CD8+ T cells and elevated protein levels of programmed cell death ligand 1 (PD-L1) were associated with progression-free survival (PFS). T-cell receptor (TCR) sequencing revealed that diverse infiltrating TCR repertoire at baseline was prognostic. We found no associations between panel-based tumor mutation burden (TMB) or specific genetic aberrations with PFS in this study. Through a pan-cancer gene co-expression network analysis, we developed a novel tumor-agnostic Pediatric Cytotoxicity and Antigen Presentation (PedCAP) signature that was associated with improved PFS in the iMATRIX-atezo study. Our study highlights features of immune response in pediatric cancers when treated with immune checkpoint inhibitors and provides a multi-biomarker pediatric immunogram framework to guide prospective clinical trials in pediatric cancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-05T01:56:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006005","title":"A Proteogenomic Analysis of Clear Cell Renal Cell Carcinoma in a Chinese Population","description":"Clear cell renal cell carcinoma (ccRCC) is a common and aggressive subtype of renal cancer. Here we conduct a comprehensive proteogenomic analysis of 232 tumor and adjacent non-tumor tissue pairs from Chinese ccRCC patients. By comparing with tumor adjacent tissues, we find that ccRCC shows extensive metabolic dysregulation and an enhanced immune response. Molecular subtyping classifies ccRCC  tumors into three subtypes (GP1–3), among which the most aggressive GP1 exhibits the strongest immune phenotype, increased metastasis, and metabolic imbalance, linking the multi-omics-derived phenotypes to clinical outcomes of ccRCC. Nicotinamide N-methyltransferase (NNMT), a one-carbon 38 metabolic enzyme, is identified as a potential marker of ccRCC and a drug target for GP1. We demonstrate that NNMT induces DNA-dependent protein kinase catalytic subunit (DNA-PKcs) homocysteinylation, increases DNA repair, and promotes ccRCC tumor growth. This study provides insights into the biological underpinnings and prognosis assessment of ccRCC, revealing targetable metabolic vulnerabilities.","abstract":"Clear cell renal cell carcinoma (ccRCC) is a common and aggressive subtype of renal cancer. Here we conduct a comprehensive proteogenomic analysis of 232 tumor and adjacent non-tumor tissue pairs from Chinese ccRCC patients. By comparing with tumor adjacent tissues, we find that ccRCC shows extensive metabolic dysregulation and an enhanced immune response. Molecular subtyping classifies ccRCC  tumors into three subtypes (GP1–3), among which the most aggressive GP1 exhibits the strongest immune phenotype, increased metastasis, and metabolic imbalance, linking the multi-omics-derived phenotypes to clinical outcomes of ccRCC. Nicotinamide N-methyltransferase (NNMT), a one-carbon 38 metabolic enzyme, is identified as a potential marker of ccRCC and a drug target for GP1. We demonstrate that NNMT induces DNA-dependent protein kinase catalytic subunit (DNA-PKcs) homocysteinylation, increases DNA repair, and promotes ccRCC tumor growth. This study provides insights into the biological underpinnings and prognosis assessment of ccRCC, revealing targetable metabolic vulnerabilities.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-05T07:50:18+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006006","title":"Whole Exome sequencing of colorectal cancer patients (SG-BULK)","description":"The study was approved by the institutional review board of Singhealth (2018-2795). Ten 5-µm tissue sections were cut using standard microtomy techniques. Each collected cell population was then extracted using the allprep kit. Extracted material was then quantified using a Qubit fluorometer. DNA-seq libraries were captured to exome regions using xGen Exome Research Panel v1.0 (IDT), and libraries were prepared using the KAPA Hyper prep kit. DNA libraries were sequenced to a target depth of ×200 for tumor sample, ×100 for normal samples on the Illumina HiSeq platform.","abstract":"The study was approved by the institutional review board of Singhealth (2018-2795). Ten 5-µm tissue sections were cut using standard microtomy techniques. Each collected cell population was then extracted using the allprep kit. Extracted material was then quantified using a Qubit fluorometer. DNA-seq libraries were captured to exome regions using xGen Exome Research Panel v1.0 (IDT), and libraries were prepared using the KAPA Hyper prep kit. DNA libraries were sequenced to a target depth of ×200 for tumor sample, ×100 for normal samples on the Illumina HiSeq platform.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-07T04:55:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006007","title":"Genomic and transcriptome analysis for intrahepatic cholangiocarcinoma","description":null,"abstract":"Intrahepatic cholangiocarcinomas (iCCs) are characterized by their rarity, difficulty in diagnosis, and overall poor prognosis. We performed comprehensive genomic and transcriptomic characterization of treatment-naive iCC. Whole transcriptome analyses identified two prognostic subtypes, concordant with previous reports. This study reports a large-scale multiomics analysis of iCC. The findings could assist in patient stratification with iCCs and in developing rational therapeutic strategies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-07T06:31:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006008","title":"PROJET DREPANOCYTOSE ET PALUDISME","description":"The goal is to study and specify the response to treatment against Plasmodium falciparum malaria in subjects with sickle cell disease in order to propose to the National Malaria Control Program of Côte d'Ivoire effective prevention and treatment strategies for this population at risk.","abstract":"The goal is to study and specify the response to treatment against Plasmodium falciparum malaria in subjects with sickle cell disease in order to propose to the National Malaria Control Program of Côte d'Ivoire effective prevention and treatment strategies for this population at risk.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-07T09:56:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006009","title":"CCL22 chemokine mutations drive natural killer cell lymphoproliferative disease by biasing GPCR signaling","description":"Chronic lymphoproliferative disorder of natural killer cells (CLPD-NK) is characterized by clonal expansion of NK cells of incompletely understood genomic basis. Here, we report somatic mutations in the chemokine gene CCL22 as the hallmark of a distinct subset of CLPD-NK. CCL22 mutations were enriched at highly conserved residues, were mutually exclusive of STAT3 mutations, and were associated with gene expression similar to normal CD16dim/CD56bright NK cells. Mechanistically, the mutations resulted in ligand-biased chemokine receptor signaling, with decreased internalization of the G-protein-coupled receptor for CCL22, CCR4, via impaired β-arrestin recruitment. This resulted in increased cell chemotaxis in vitro, bidirectional crosstalk with the hematopoietic microenvironment, and enhanced NK cell proliferation in vivo in transgenic human IL-15 mice. Somatic CCL22 mutations illustrate a novel mechanism of tumor formation in which gain-of-function chemokine mutations promote tumorigenesis by biased G-protein-coupled receptor signaling and dysregulation of microenvironmental crosstalk.","abstract":"Chronic lymphoproliferative disorder of natural killer cells (CLPD-NK) is characterized by clonal expansion of NK cells of incompletely understood genomic basis. Here, we report somatic mutations in the chemokine gene CCL22 as the hallmark of a distinct subset of CLPD-NK. CCL22 mutations were enriched at highly conserved residues, were mutually exclusive of STAT3 mutations, and were associated with gene expression similar to normal CD16dim/CD56bright NK cells. Mechanistically, the mutations resulted in ligand-biased chemokine receptor signaling, with decreased internalization of the G-protein-coupled receptor for CCL22, CCR4, via impaired β-arrestin recruitment. This resulted in increased cell chemotaxis in vitro, bidirectional crosstalk with the hematopoietic microenvironment, and enhanced NK cell proliferation in vivo in transgenic human IL-15 mice. Somatic CCL22 mutations illustrate a novel mechanism of tumor formation in which gain-of-function chemokine mutations promote tumorigenesis by biased G-protein-coupled receptor signaling and dysregulation of microenvironmental crosstalk.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-07T11:49:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006010","title":"Human genome-wide variations in the Massim region","description":"The Massim, a cultural region encompassing the southeastern tip of mainland Papua New\nGuinea (PNG) and nearby islands, is famous for the Kula trading network, in which\ndifferent valuables circulate in different directions among the islands. To explore Massim\ngenetic history, we generated genome-wide data from across the region and found variable\nlevels of Papuan-related (indigenous) ancestry, including a novel ancestry associated with\nRossel Island, and Austronesian-related ancestry that arrived later. We find genetic\nevidence for different patterns of contact across PNG, the Massim, and the Bismarck and\nSolomon Archipelagoes for Austronesian-related vs. Papuan-related ancestry, with more\ngeographic restriction for the latter. Moreover, Kula-practicing groups share more genetic\nsimilarity than do other groups, and this likely predates the origin of Kula, suggesting that\nhigh between-group contact facilitated the formation of Kula. Our study provides the first\ncomprehensive genome-wide assessment of Massim inhabitants and new insights into the\nfascinating Kula system.","abstract":"The Massim, a cultural region encompassing the southeastern tip of mainland Papua New\nGuinea (PNG) and nearby islands, is famous for the Kula trading network, in which\ndifferent valuables circulate in different directions among the islands. To explore Massim\ngenetic history, we generated genome-wide data from across the region and found variable\nlevels of Papuan-related (indigenous) ancestry, including a novel ancestry associated with\nRossel Island, and Austronesian-related ancestry that arrived later. We find genetic\nevidence for different patterns of contact across PNG, the Massim, and the Bismarck and\nSolomon Archipelagoes for Austronesian-related vs. Papuan-related ancestry, with more\ngeographic restriction for the latter. Moreover, Kula-practicing groups share more genetic\nsimilarity than do other groups, and this likely predates the origin of Kula, suggesting that\nhigh between-group contact facilitated the formation of Kula. Our study provides the first\ncomprehensive genome-wide assessment of Massim inhabitants and new insights into the\nfascinating Kula system.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-07T13:17:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006011","title":"Genomic diversity of Vietnamese","description":"This study assess the genomic diversity of 22 ethnolinguistic groups in Vietnam","abstract":"This study assess the genomic diversity of 22 ethnolinguistic groups in Vietnam","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-07T13:34:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006012","title":"To determine the transcriptional profiles of Ovarian carcinomas (UW cohort)","description":"Specific BRCA and immune configurations determine optimal response to platinum-based chemotherapy in triple negative breast and ovarian carcinomas (UW_OvCa_RNAseq)","abstract":"Specific BRCA and immune configurations determine optimal response to platinum-based chemotherapy in triple negative breast and ovarian carcinomas (UW_OvCa_RNAseq)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-07T17:02:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006013","title":"Single cell RNA sequencing of colorectal cancer patients (CRC-SG1)","description":"Fresh single-cell suspensions were loaded into the Chromium system (10x Genomics) targeting 5,000 cells per well. Barcoded sequencing libraries were generated using 3’v3 Reagent kit.","abstract":"Fresh single-cell suspensions were loaded into the Chromium system (10x Genomics) targeting 5,000 cells per well. Barcoded sequencing libraries were generated using 3’v3 Reagent kit.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-08T06:46:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006014","title":"Y chromosomes of Island South East Asia","description":null,"abstract":"Island Southeast Asia and Oceania host one of the world’s richest assemblages of human phenotypic, linguistic and cultural diversity. Despite this, the region’s male genetic lineages are globally among the last to remain unresolved. We compiled ~9.7 Mb of Y chromosome sequence from a diverse sample of over 380 men from this region, including 152 first reported here. The granularity of this dataset allows us to fully resolve and date the regional Y chromosome phylogeny. This new high-resolution tree confirms two main population bursts: multiple rapid diversifications following the region’s initial settlement ~50 kya, and extensive expansions &lt;6 kya. Notably, ~40-25 kya the deep rooting local lineages of C-M130, M-P256, and S-B254 show almost no further branching events in Island Southeast Asia, New Guinea and Australia, matching a similar pause in diversification seen in maternal mitochondrial DNA lineages. The main local lineages start diversifying ~25 kya, at the time of the Last Glacial Maximum (LGM). This improved Y chromosome topology highlights localized events with important historical implications, including pre-Holocene contact between Mainland and Island Southeast Asia, ongoing interactions between Australia and the Papuan world, and a sustained period of diversification following the flooding of the ancient Sunda and Sahul continents as the insular landscape of today formed. The high-resolution phylogeny of the Y chromosome presented here thus enables a detailed exploration of past isolation, interaction and change in one of the world’s least understood regions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006015","title":"DNA methylation profiles of samples included in the EORTC 26091 TAVAREC trial","description":null,"abstract":"The TAVAREC trial was a randomized, open-label phase 2 trial assessing the benefit of the addition of the angiogenesis inhibitor bevacizumab to treatment with temozolomide in patients with a first enhancing recurrence of WHO grade 2 or 3 glioma without 1p/19q codeletion. We evaluated the prognostic significance of genome wide DNA methylation profiles and copy number variations on the TAVAREC trial samples.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-08T15:33:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006016","title":"Drug-induced epigenomic plasticity reprograms circadian rhythm regulation to drive prostate cancer towards androgen-independence (RNA-seq)","description":"Understanding how prostate cancer cells adapt to AR-targeted interventions is critical for identifying novel drug targets to improve the clinical management of treatment-resistant disease. Our study revealed an enzalutamide-induced epigenetic plasticity towards pro-survival signaling, and uncovered circadian regulator ARNTL as an acquired vulnerability after AR inhibition, presenting a novel clinical lead for therapeutic development.","abstract":"Understanding how prostate cancer cells adapt to AR-targeted interventions is critical for identifying novel drug targets to improve the clinical management of treatment-resistant disease. Our study revealed an enzalutamide-induced epigenetic plasticity towards pro-survival signaling, and uncovered circadian regulator ARNTL as an acquired vulnerability after AR inhibition, presenting a novel clinical lead for therapeutic development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-09T08:37:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006017","title":"Drug-induced epigenomic plasticity reprograms circadian rhythm regulation to drive prostate cancer towards androgen-independence (ChIP-seq)","description":"Understanding how prostate cancer cells adapt to AR-targeted interventions is critical for identifying novel drug targets to improve the clinical management of treatment-resistant disease. Our study revealed an enzalutamide-induced epigenetic plasticity towards pro-survival signaling, and uncovered circadian regulator ARNTL as an acquired vulnerability after AR inhibition, presenting a novel clinical lead for therapeutic development.","abstract":"Understanding how prostate cancer cells adapt to AR-targeted interventions is critical for identifying novel drug targets to improve the clinical management of treatment-resistant disease. Our study revealed an enzalutamide-induced epigenetic plasticity towards pro-survival signaling, and uncovered circadian regulator ARNTL as an acquired vulnerability after AR inhibition, presenting a novel clinical lead for therapeutic development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-09T08:37:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006018","title":"CRC9_iBE3NGG_IFNG8_MC_09_02_21","description":"1 sample is pure plasmid DNA and 6 samples are cell pellets for genomic DNA extraction.\nCRISPR PCR1 and PCR2 indexing - Please use standard Kozuke primers.","abstract":"1 sample is pure plasmid DNA and 6 samples are cell pellets for genomic DNA extraction.\nCRISPR PCR1 and PCR2 indexing - Please use standard Kozuke primers.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006019","title":"Disease specific alterations in the olfactory mucosa of patients with Alzheimer’s disease","description":"OOlfactory dysfunction manifests early in several neurodegenerative disorders. Olfaction is orchestrated by olfactory mucosal cells located in the upper nasal cavity. However, it is unclear how this tissue reflects key neurodegenerative features in Alzheimer’s disease. Here we report that Alzheimer´s disease olfactory mucosal cells secrete toxic amyloid-beta. We detail cell-type-specific gene expression patterns, unveiling 147 differentially expressed disease-associated genes compared to the cognitively healthy controls, and 5 distinct populations in globose basal cell -, myofibroblast-, and fibroblast/ stromal – like cells in vitro. Overall, coordinated alteration of RNA and protein metabolism, inflammatory processes and signal transduction were observed in multiple cell populations, suggesting a key role in pathophysiology. Our results demonstrate the potential of olfactory cell cultures in modelling Alzheimer´s disease. Moreover, for the first time we provide single cell data on olfactory mucosa in Alzheimer´s disease for investigating molecular and cellular mechanisms associated with the disease.","abstract":"OOlfactory dysfunction manifests early in several neurodegenerative disorders. Olfaction is orchestrated by olfactory mucosal cells located in the upper nasal cavity. However, it is unclear how this tissue reflects key neurodegenerative features in Alzheimer’s disease. Here we report that Alzheimer´s disease olfactory mucosal cells secrete toxic amyloid-beta. We detail cell-type-specific gene expression patterns, unveiling 147 differentially expressed disease-associated genes compared to the cognitively healthy controls, and 5 distinct populations in globose basal cell -, myofibroblast-, and fibroblast/ stromal – like cells in vitro. Overall, coordinated alteration of RNA and protein metabolism, inflammatory processes and signal transduction were observed in multiple cell populations, suggesting a key role in pathophysiology. Our results demonstrate the potential of olfactory cell cultures in modelling Alzheimer´s disease. Moreover, for the first time we provide single cell data on olfactory mucosa in Alzheimer´s disease for investigating molecular and cellular mechanisms associated with the disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-09T13:16:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006020","title":"Methylome sequencing of cell-free DNA and RRBS of solid tissue","description":"Early cancer detection by cell-free DNA (cfDNA) faces multiple challenges: low fraction of tumor cfDNA, molecular heterogeneity of cancer, and sample sizes not sufficient to reflect diverse patient population. We develop a cancer detection approach to address these challenges. It consists of an assay, cfMethyl-Seq, for cost-effective sequencing of cfDNA methylome (with &gt;12-fold enrichment over whole genome bisulfite sequencing in CpG islands), and a computational method to extract methylation information and diagnose patients. Applying our system to 408 colon, liver, lung, and stomach cancer patients and controls, at 97.9% specificity we achieve 80.7% and 74.5% sensitivity in detecting all-stage and early-stage cancer, and 89.1% and 85.0% accuracy for locating tissue-of-origin of all-stage and early-stage cancer, respectively. Our approach cost-effectively retains methylome profiles of cancer abnormalities, thereby permitting the classification models to learn new features as training cohorts grow, and expanding their scope to other cancer types.","abstract":"Early cancer detection by cell-free DNA (cfDNA) faces multiple challenges: low fraction of tumor cfDNA, molecular heterogeneity of cancer, and sample sizes not sufficient to reflect diverse patient population. We develop a cancer detection approach to address these challenges. It consists of an assay, cfMethyl-Seq, for cost-effective sequencing of cfDNA methylome (with &gt;12-fold enrichment over whole genome bisulfite sequencing in CpG islands), and a computational method to extract methylation information and diagnose patients. Applying our system to 408 colon, liver, lung, and stomach cancer patients and controls, at 97.9% specificity we achieve 80.7% and 74.5% sensitivity in detecting all-stage and early-stage cancer, and 89.1% and 85.0% accuracy for locating tissue-of-origin of all-stage and early-stage cancer, respectively. Our approach cost-effectively retains methylome profiles of cancer abnormalities, thereby permitting the classification models to learn new features as training cohorts grow, and expanding their scope to other cancer types.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-09T21:38:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006021","title":"The neo-open reading frame peptides that comprise the tumor framome are a rich source of neoantigens for cancer immunotherapy","description":"Identification of immunogenic cancer neoantigens as targets for therapy is challenging. Here, we integrate whole genome and long-read transcript sequencing of cancers to identify the collection of neo-open reading frame peptides (NOPs) expressed in tumors. We termed this collection of NOPs the tumor framome. NOPs represent tumor-specific peptides that are different from wild-type proteins and may be strongly immunogenic. We describe a class of hidden NOPs that derive from structural genomic variants involving an upstream protein coding gene driving expression and translation of non-coding regions of the genome downstream of a rearrangement breakpoint, i.e. where no gene annotation or evidence for transcription exists. The entire collection of NOPs represents a vast number of possible neoantigens particularly in tumors with many structural genomic variants and a low number of missense mutations. We show that NOPs are immunogenic and epitopes derived from NOPs can bind to MHC class I molecules. Finally, we provide evidence for the presence of memory T cells specific for hidden NOPs in peripheral blood from a patient with lung cancer. This work highlights NOPs as a major source of possible neoantigens for personalized cancer immunotherapy and provides a rationale for analyzing the complete cancer genome and transcriptome as a basis for detection of NOPs.","abstract":"Immunotherapy has provided a major leap forward in the treatment of cancer. Major efforts focus on development of personalized neoantigen-directed immunotherapies, such as cancer vaccines and T-cell therapies. However, identification of highly immunogenic neoantigens as immunotherapy target from a tumor sample is challenging. Here, we integrate cancer genome and full-length transcript sequencing with a bioinformatics pipeline to identify the entire collection of novel open reading frames peptides (NOPs) expressed in tumors, which we term the framome. As opposed to neoantigens derived from missense mutations, NOPs represent long tumor-specific peptides that are completely different from wild-type proteins and are recognized as strongly immunogenic. We describe an uncharacterized class of hidden NOPs, which derive from structural genomic variants involving an upstream known protein coding gene that directly drives expression of non-coding regions of the genome downstream of a rearrangement breakpoint. NOPs are prevalent in major cancer types and represent a vast amount of possible neoantigens particularly in tumors with many (complex) structural variants and a low number of missense mutations. Our work highlights a novel source of neoantigens for personalized immunotherapies and provides a workflow for analyzing the complete cancer genome and transcriptome as a basis for systematic detection of NOPs.","study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-08T10:34:12.720707+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006022","title":"Whole-exome sequencing of glioblastomas with long-term relapse interval","description":"Treatment options for GBM patients have not changed over the last 15 years, and the success of targeted therapy or immunotherapy has been disappointinglimited. Thus, the standard of care for GBM patients remains surgical resection followed by concomitant DNA alkylating agent therapy with temozolomide (TMZ) and radiation therapy (RT). However, the time to relapse is generally short (6.9 months on average) owing to the tumor’s ability to infiltrate normal parenchyma and its intrinsic resistance to radio-chemotherapy. Due to the lack of alternative treatment options, elucidating underlying resistance mechanism has come into major focus of research, with the hope for opening new ways of therapeutic intervention overcoming resistance.\n\nTo explore therapy resistance driving events, we performed a study using a single-centric collective of matched pairs of therapy-naïve and post-therapeuticc tissue from GBM patients, selected based on a maximally long interval between resections of the initial and the recurrent tumors. This rare collective was analyzed by whole exome sequencing (WES), mRNA expression and miRNA expression profiling.","abstract":"Treatment options for GBM patients have not changed over the last 15 years, and the success of targeted therapy or immunotherapy has been disappointinglimited. Thus, the standard of care for GBM patients remains surgical resection followed by concomitant DNA alkylating agent therapy with temozolomide (TMZ) and radiation therapy (RT). However, the time to relapse is generally short (6.9 months on average) owing to the tumor’s ability to infiltrate normal parenchyma and its intrinsic resistance to radio-chemotherapy. Due to the lack of alternative treatment options, elucidating underlying resistance mechanism has come into major focus of research, with the hope for opening new ways of therapeutic intervention overcoming resistance.\n\nTo explore therapy resistance driving events, we performed a study using a single-centric collective of matched pairs of therapy-naïve and post-therapeuticc tissue from GBM patients, selected based on a maximally long interval between resections of the initial and the recurrent tumors. This rare collective was analyzed by whole exome sequencing (WES), mRNA expression and miRNA expression profiling.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-10T08:56:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006023","title":"Blocking unwanted sequences by target specific high affinity binding oligonucleotides during transcriptome library preparation","description":null,"abstract":"RNA sequencing has become the gold standard for transcriptome analysis but comes with an inherent limitation with respect to quantification of low abundant transcripts. In contrast to microarray technology, RNA-sequencing reads are proportionally divided across transcripts. Therefore, low abundant RNAs can be out-competed by highly abundant—and sometimes non-informative—RNA species. We developed an easy-to-use strategy based on high-affinity RNA-binding oligonucleotides to block reverse transcription and PCR-amplification of specific RNA transcripts, hereby preventing them from ending up in the RNA-sequencing library. To demonstrate the broad application potential of our method, we applied it to various abundant RNA’s and library preparation strategies, including YRNAs in small RNA-sequencing of human plasma samples, mitochondrial rRNAs in both 3’ end sequencing and long-read sequencing, and MALAT1 in single-cell 3’ end sequencing. We demonstrate that the blocking strategy is extremely efficient, reproducible and specific and results in better transcriptome coverage and complexity. Our method does not require major modifications of the library preparation procedure apart from adding blocking oligonucleotides to the RT reaction and can thus be easily integrated in virtually any RNA library preparation protocol.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006024","title":"Application of high-throughput, high-depth, targeted single-nucleus DNA sequencing in pancreatic cancer","description":"Despite insights gained by bulk DNA sequencing of cancer it remains challenging to resolve the admixture of normal and tumor cells, and/or of distinct tumor subclones; high throughput single-cell DNA sequencing circumvents these and brings cancer genomic studies to higher resolution. However, its application has been limited to liquid tumors or a small batch of solid tumors, mainly because of the lack of a scalable workflow to process solid tumor samples. Here we optimized a highly automated nuclei extraction workflow that achieved fast and reliable targeted single-nucleus DNA library preparation of 38 samples from 16 pancreatic ductal adenocarcinoma (PDAC) patients, with an average library yield per sample of 2867 single nuclei. We demonstrate that this workflow not only performs well using low cellularity or low tumor purity samples but reveals novel genomic evolution patterns of PDAC as well.","abstract":"Despite insights gained by bulk DNA sequencing of cancer it remains challenging to resolve the admixture of normal and tumor cells, and/or of distinct tumor subclones; high throughput single-cell DNA sequencing circumvents these and brings cancer genomic studies to higher resolution. However, its application has been limited to liquid tumors or a small batch of solid tumors, mainly because of the lack of a scalable workflow to process solid tumor samples. Here we optimized a highly automated nuclei extraction workflow that achieved fast and reliable targeted single-nucleus DNA library preparation of 38 samples from 16 pancreatic ductal adenocarcinoma (PDAC) patients, with an average library yield per sample of 2867 single nuclei. We demonstrate that this workflow not only performs well using low cellularity or low tumor purity samples but reveals novel genomic evolution patterns of PDAC as well.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-10T14:49:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006025","title":"Papuan Y chromosome Diversity Panel","description":"Island Southeast Asia and Oceania host one of the world’s richest assemblages of human phenotypic, linguistic and cultural diversity. Despite this, the region’s male genetic lineages are globally among the last to remain unresolved. We compiled ~9.7 Mb of Y chromosome sequence from a diverse sample of over 380 men from this region, including 152 first reported here. The granularity of this dataset allows us to fully resolve and date the regional Y chromosome phylogeny. This new high-resolution tree confirms two main population bursts: multiple rapid diversifications following the region’s initial settlement ~50 kya, and extensive expansions &lt;6 kya. Notably, ~40-25 kya the deep rooting local lineages of C-M130, M-P256, and S-B254 show almost no further branching events in Island Southeast Asia, New Guinea and Australia, matching a similar pause in diversification seen in maternal mitochondrial DNA lineages. The main local lineages start diversifying ~25 kya, at the time of the Last Glacial Maximum. This improved Y chromosome topology highlights localized events with important historical implications, including pre-Holocene contact between Mainland and Island Southeast Asia, potential interactions between Australia and the Papuan world, and a sustained period of diversification following the flooding of the ancient Sunda and Sahul continents as the insular landscape observed today formed. The high-resolution phylogeny of the Y chromosome presented here thus enables a detailed exploration of","abstract":"Island Southeast Asia and Oceania host one of the world’s richest assemblages of human phenotypic, linguistic and cultural diversity. Despite this, the region’s male genetic lineages are globally among the last to remain unresolved. We compiled ~9.7 Mb of Y chromosome sequence from a diverse sample of over 380 men from this region, including 152 first reported here. The granularity of this dataset allows us to fully resolve and date the regional Y chromosome phylogeny. This new high-resolution tree confirms two main population bursts: multiple rapid diversifications following the region’s initial settlement ~50 kya, and extensive expansions &lt;6 kya. Notably, ~40-25 kya the deep rooting local lineages of C-M130, M-P256, and S-B254 show almost no further branching events in Island Southeast Asia, New Guinea and Australia, matching a similar pause in diversification seen in maternal mitochondrial DNA lineages. The main local lineages start diversifying ~25 kya, at the time of the Last Glacial Maximum. This improved Y chromosome topology highlights localized events with important historical implications, including pre-Holocene contact between Mainland and Island Southeast Asia, potential interactions between Australia and the Papuan world, and a sustained period of diversification following the flooding of the ancient Sunda and Sahul continents as the insular landscape observed today formed. The high-resolution phylogeny of the Y chromosome presented here thus enables a detailed exploration of","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-11T12:25:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006026","title":"IYDP Indonesian Y chromosome Diversity Project","description":null,"abstract":"We compiled Y chromosome high coverage sequence from a diverse sample across the broad geography of Indonesia and New Guinea. The granularity of this dataset allows us to fully resolve and date the regional Y chromosome phylogeny and highlight localized events with important historical implications, including pre-Holocene contact between Mainland and Island Southeast Asia, potential interactions between Australia and the Papuan world, and a sustained period of diversification following the flooding of the ancient Sunda and Sahul continents as the insular landscape observed today formed. We extracted 126 Y chromosomes from the whole genome sequences of individuals form this broad range of geography.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006027","title":"Targeted analysis of cell-free circulating tumor DNA is suitable for early relapse and actionable target detection in patients with neuroblastoma","description":null,"abstract":"Purpose: Treating refractory or relapsed neuroblastoma remains challenging. Monitoring body fluids for tumor-derived molecular information indicating minimal residual disease supports more frequent diagnostic surveillance and may have the power to detect resistant subclones before they give rise to relapses. If actionable targets are identified from liquid biopsies, targeted treatment options can be considered earlier.\nExperimental design: Droplet digital PCR assays assessing MYCN and ALK copy numbers and allelic frequencies of ALK p.F1174L and ALK p.R1275Q mutations were applied to longitudinally collected liquid biopsies and matched tumor tissue samples from 31 patients with high-risk neuroblastoma. Total cell-free DNA (cfDNA) levels and marker detection were compared with data from routine clinical diagnostics.\nResults: Total cfDNA concentrations in blood plasma from patients with high-risk neuroblastoma were higher than in healthy controls and consistently correlated with neuron-specific enolase levels and lactate dehydrogenase activity but not with 123I-meta-iodobenzylguanidine scores at relapse diagnosis. Targeted cfDNA diagnostics proved superior for early relapse detection to all current diagnostics in two patients. Marker analysis in cfDNA indicated intratumor heterogeneity for cell clones harboring MYCN amplifications and druggable ALK alterations that were not detectable in matched tumor tissue samples in 17 patients from our cohort. Proof-of-concept is provided for molecular target detection in cerebrospinal fluid from patients with isolated CNS relapses.\nConclusions: Tumor-specific alterations can be identified and monitored during disease course in liquid biopsies from pediatric patients with high-risk neuroblastoma. This approach to cfDNA surveillance warrants further prospective validation and exploitation for diagnostic purposes and to guide therapeutic decisions.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-11T15:37:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006028","title":"IYDP Indonesian Y chromosome Diversity Project","description":"Island Southeast Asia and Oceania host one of the world’s richest assemblages of human phenotypic, linguistic and cultural diversity. We compiled ~9.7 Mb of Y chromosome sequence from a diverse sample of over 380 men from this region, including 126 from Indonesian islands, first reported here. The granularity of this dataset allows us to fully resolve and date the regional Y chromosome phylogeny. This improved Y chromosome topology highlights localized events with important historical implications, including pre-Holocene contact between Mainland and Island Southeast Asia, ongoing interactions between Australia and the Papuan world, and a sustained period of diversification following the flooding of the ancient Sunda and Sahul continents as the insular landscape of today formed. The high-resolution phylogeny of the Y chromosome presented here thus enables a detailed exploration of past isolation, interaction and change in one of the world’s least understood regions.","abstract":"Island Southeast Asia and Oceania host one of the world’s richest assemblages of human phenotypic, linguistic and cultural diversity. We compiled ~9.7 Mb of Y chromosome sequence from a diverse sample of over 380 men from this region, including 126 from Indonesian islands, first reported here. The granularity of this dataset allows us to fully resolve and date the regional Y chromosome phylogeny. This improved Y chromosome topology highlights localized events with important historical implications, including pre-Holocene contact between Mainland and Island Southeast Asia, ongoing interactions between Australia and the Papuan world, and a sustained period of diversification following the flooding of the ancient Sunda and Sahul continents as the insular landscape of today formed. The high-resolution phylogeny of the Y chromosome presented here thus enables a detailed exploration of past isolation, interaction and change in one of the world’s least understood regions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-11T16:32:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006029","title":"Cerebrospinal fluid methylome-based liquid biopsies","description":null,"abstract":"In this study we show that cerebrospinal fluid (CSF) DNA methylation profiling can serve as a highly reliable liquid biopsy-based diagnostic approach to avoid risks related to invasive neurosurgery. We demonstrate specific DNA methylation signatures that can be utilized to accurately differentiate common intra-axial malignant brain tumors using CSF samples and examine the validity of approaches integrating CSF methylomes with tissue-based signatures.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006030","title":"Whole genome sequencing of colorectal cancer patients (SG-BULK-1)","description":"The study was approved by the institutional review board of Singhealth (2018-2795). Ten 5-µm tissue sections were cut using standard microtomy techniques. Each collected cell population was then extracted using the allprep kit. Extracted material was then quantified using a Qubit fluorometer.","abstract":"The study was approved by the institutional review board of Singhealth (2018-2795). Ten 5-µm tissue sections were cut using standard microtomy techniques. Each collected cell population was then extracted using the allprep kit. Extracted material was then quantified using a Qubit fluorometer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-13T07:34:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006031","title":"Genomewide copy number alteration screening of circulating plasma DNA","description":"Early cancer diagnosis might improve survival rates. As circulating tumor DNA (ctDNA) carries cancer-specific modifications, it has great potential as a noninvasive biomarker for detection of incipient tumors. We collected cell-free DNA (cfDNA) samples of 1002 elderly without a prior malignancy, carried out whole-genome massive parallel sequencing and scrutinized the mapped sequences for the presence of (sub)chromosomal copy number alterations (CNAs) predictive for a malignancy. When imbalances were detected, 6-monthly clinical follow-up was carried out.","abstract":"Early cancer diagnosis might improve survival rates. As circulating tumor DNA (ctDNA) carries cancer-specific modifications, it has great potential as a noninvasive biomarker for detection of incipient tumors. We collected cell-free DNA (cfDNA) samples of 1002 elderly without a prior malignancy, carried out whole-genome massive parallel sequencing and scrutinized the mapped sequences for the presence of (sub)chromosomal copy number alterations (CNAs) predictive for a malignancy. When imbalances were detected, 6-monthly clinical follow-up was carried out.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-13T09:03:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006032","title":"Nanoseq_of_FFPE_oesophagus","description":"This is a pilot project to see if Nanoseq is possible with FFPE material,","abstract":"This is a pilot project to see if Nanoseq is possible with FFPE material,","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006033","title":"Genome-wide DNA Methylation Data from Illumina HumanMethylationEPIC arrays for whole blood samples from 403 healthy individuals","description":"Genome-wide DNA Methylation Data from Illumina HumanMethylationEPIC arrays for whole blood samples from 403 healthy individuals. Additional associated phenotype information is available for all individuals included in this study directly from CIBMTR. Data are available under controlled access release upon reasonable request and execution of a data use agreement. Requests should be submitted to CIBMTR at info-request@mcw.edu and include the study reference IB17-04.","abstract":"Genome-wide DNA Methylation Data from Illumina HumanMethylationEPIC arrays for whole blood samples from 403 healthy individuals. Additional associated phenotype information is available for all individuals included in this study directly from CIBMTR. Data are available under controlled access release upon reasonable request and execution of a data use agreement. Requests should be submitted to CIBMTR at info-request@mcw.edu and include the study reference IB17-04.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-14T19:47:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006034","title":"The clinical utility of genomics in childhood cancer extends beyond targetable mutations","description":"Survival of children with relapsed cancer remains unacceptably low. Cancer genomic profiling may identify new therapeutic options, enhance diagnostic accuracy, and improve understanding of tumors’ origins and continued evolution. We deeply sequenced 864 cancer-associated genes and the complete genomes and transcriptomes for 300 pediatric and adolescent/young adult (AYA) patients with poor prognosis or rare tumors. Using integrative somatic-germline analyses, we assessed the clinical utility of cancer genomics in this population. We analyzed tumor mutational signatures and burden to interrogate the relevance of germline variants in DNA repair genes and the impact of therapeutic exposures on tumor evolution. We also evaluated the frequency of changes to tumor drivers and therapeutic targets at relapse in those with serial samples. Integrative analysis yielded clinically actionable variants in a majority of patients.  Improved diagnostic accuracy led to modified management in a subset. Therapeutically targetable variants were of unanticipated timing and type, with many of these derived from the germline. Enrichment in corroborating mutational signature 3 (‘BRCAness’) in patients with germline homologous recombination defects suggests they are drivers of pediatric cancers and potential targets for PARP inhibition. We show that mutation burden, which may in part be driven by prior therapeutic exposures, was significantly elevated in a minority of patients. Over one-third of patients with sequential samples analyzed showed a change in therapeutically-targetable drivers. Comprehensive somatic-germline cancer genomic profiling is useful at multiple points in the care trajectory for pediatric/AYA patients, supporting its integration into early clinical management. Re-biopsy at the time of relapse should be considered, and specific attention to mutational burden is indicated. Defective DNA repair genes in the germline may represent important targetable drivers.","abstract":"Survival of children with relapsed cancer remains unacceptably low. Cancer genomic profiling may identify new therapeutic options, enhance diagnostic accuracy, and improve understanding of tumors’ origins and continued evolution. We deeply sequenced 864 cancer-associated genes and the complete genomes and transcriptomes for 300 pediatric and adolescent/young adult (AYA) patients with poor prognosis or rare tumors. Using integrative somatic-germline analyses, we assessed the clinical utility of cancer genomics in this population. We analyzed tumor mutational signatures and burden to interrogate the relevance of germline variants in DNA repair genes and the impact of therapeutic exposures on tumor evolution. We also evaluated the frequency of changes to tumor drivers and therapeutic targets at relapse in those with serial samples. Integrative analysis yielded clinically actionable variants in a majority of patients.  Improved diagnostic accuracy led to modified management in a subset. Therapeutically targetable variants were of unanticipated timing and type, with many of these derived from the germline. Enrichment in corroborating mutational signature 3 (‘BRCAness’) in patients with germline homologous recombination defects suggests they are drivers of pediatric cancers and potential targets for PARP inhibition. We show that mutation burden, which may in part be driven by prior therapeutic exposures, was significantly elevated in a minority of patients. Over one-third of patients with sequential samples analyzed showed a change in therapeutically-targetable drivers. Comprehensive somatic-germline cancer genomic profiling is useful at multiple points in the care trajectory for pediatric/AYA patients, supporting its integration into early clinical management. Re-biopsy at the time of relapse should be considered, and specific attention to mutational burden is indicated. Defective DNA repair genes in the germline may represent important targetable drivers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-15T14:50:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006035","title":"WGS of iPSC from TOF patients with/without DG and healthy control","description":null,"abstract":"To verify the presence and absence of microdeletion on chromosome 22 in TOF-DG patients and TOF-ND patients/control, respectively.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-15T17:23:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006036","title":"RNASeq of PAX4 KO vs WT in 7 stages of differentiation from human iPSCs to BLC","description":"Transcriptomes were profiled along with the differentiation from human induced pluripotent stem cell (iPSC) to beta-like cell (BLC) with PAX4 knocked out or not.","abstract":"Transcriptomes were profiled along with the differentiation from human induced pluripotent stem cell (iPSC) to beta-like cell (BLC) with PAX4 knocked out or not.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-15T21:10:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006037","title":"The KATHERINE study of adjuvant trastuzumab emtansine in HER2-positive breast cancer: analysis of patients with HER2-negative residual invasive disease on re-testing","description":"Following chemotherapy and human epidermal growth factor 2 (HER2)-targeted neoadjuvant therapy for HER2-positive early breast cancer, residual invasive breast cancer at surgery may be HER2-negative on retesting in some patients. We evaluated outcomes with T-DM1 and trastuzumab in patients randomized in the phase III KATHERINE trial based on HER2-positive central testing of the core biopsy with HER2-negative central testing on their corresponding surgical specimen.   In the 70/845 (8.3%) patients with HER2-negative residual disease on retesting at surgery, there were 11 IDFS events in the 42 trastuzumab-treated patients (26.2%) and none in the 28 T-DM1-treated patients, suggesting that T-DM1 should not be withheld in this patient population.","abstract":"Following chemotherapy and human epidermal growth factor 2 (HER2)-targeted neoadjuvant therapy for HER2-positive early breast cancer, residual invasive breast cancer at surgery may be HER2-negative on retesting in some patients. We evaluated outcomes with T-DM1 and trastuzumab in patients randomized in the phase III KATHERINE trial based on HER2-positive central testing of the core biopsy with HER2-negative central testing on their corresponding surgical specimen.   In the 70/845 (8.3%) patients with HER2-negative residual disease on retesting at surgery, there were 11 IDFS events in the 42 trastuzumab-treated patients (26.2%) and none in the 28 T-DM1-treated patients, suggesting that T-DM1 should not be withheld in this patient population.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-16T01:50:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006038","title":"GINS3 fibroblast RNAseq","description":"The eukaryotic CDC45/MCM2-7/GINS (CMG) DNA helicase unwinds the DNA double helix during DNA replication. We report the identification of individuals presenting with a Meier-Gorlin syndrome (MGS) like phenotype, secondary to hypomorphic variants in the GINS3 gene.  To verify whether the GINS3 variant affected the transcriptome, RNA-seq was performed from 3 fibroblast cultures derived from a patient with compound heterozygous GINS3 variants, and 1 replicate of fibroblasts derived from each of the two parents.","abstract":"The eukaryotic CDC45/MCM2-7/GINS (CMG) DNA helicase unwinds the DNA double helix during DNA replication. We report the identification of individuals presenting with a Meier-Gorlin syndrome (MGS) like phenotype, secondary to hypomorphic variants in the GINS3 gene.  To verify whether the GINS3 variant affected the transcriptome, RNA-seq was performed from 3 fibroblast cultures derived from a patient with compound heterozygous GINS3 variants, and 1 replicate of fibroblasts derived from each of the two parents.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-16T19:49:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006039","title":"Whole Genome sequencing of colorectal cancer patients (SG-BULK-2)","description":"The study was approved by the institutional review board of Singhealth (2018-2795). Ten 5-µm tissue sections were cut using standard microtomy techniques. Each collected cell population was then extracted using the allprep kit. Extracted material was then quantified using a Qubit fluorometer.","abstract":"The study was approved by the institutional review board of Singhealth (2018-2795). Ten 5-µm tissue sections were cut using standard microtomy techniques. Each collected cell population was then extracted using the allprep kit. Extracted material was then quantified using a Qubit fluorometer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-17T06:48:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006040","title":"Comparison of sequencing assays for sensitive detection of circulating tumour DNA in stage IA-IV breast cancer","description":"This study compared different assays for the detection of circulating tumour DNA (ctDNA) in serial plasma from stage IA-IV breast cancer patients, targeting structural variants (SVs), single nucleotide variants (SNVs) and/or somatic copy-number aberrations (SCNAs). SV-multiplex PCR, SNV-/SV-hybrid capture, and different depths of whole-genome sequencing (WGS) were used to evaluate ctDNA levels, demonstrating concordant results. SNV-hybrid capture targeting 1,347-7,491 mutations was the most sensitive assay, detecting 67% (36/54) of samples down to an allele fraction (AF) of 0.00024%. SV-multiplex PCR, targeting 21-47 mutations, detected 63% (34/54) of samples down to 0.00047% AF and has potential as a clinical assay.","abstract":"This study compared different assays for the detection of circulating tumour DNA (ctDNA) in serial plasma from stage IA-IV breast cancer patients, targeting structural variants (SVs), single nucleotide variants (SNVs) and/or somatic copy-number aberrations (SCNAs). SV-multiplex PCR, SNV-/SV-hybrid capture, and different depths of whole-genome sequencing (WGS) were used to evaluate ctDNA levels, demonstrating concordant results. SNV-hybrid capture targeting 1,347-7,491 mutations was the most sensitive assay, detecting 67% (36/54) of samples down to an allele fraction (AF) of 0.00024%. SV-multiplex PCR, targeting 21-47 mutations, detected 63% (34/54) of samples down to 0.00047% AF and has potential as a clinical assay.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-17T08:25:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006041","title":"A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening","description":null,"abstract":"Polygenic risk score (PRS) offers attractive possibilities for identifying individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we performed a genome-wide association study (GWAS) for nasopharyngeal carcinoma (NPC), using a multi-center study (4506 NPC cases and 5384 controls). We derived a PRS from the GWAS and validate its performance in additional study samples.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006042","title":"Anti-Cancer Therapies Induce Mutations in Adult Stem Cells in a Tissue-Specific Manner","description":null,"abstract":"Systematic analyses of genome-wide mutation profiles of cancer cells and cultured cells have recently shown that some anticancer treatments are highly mutagenic. Since most treatments are typically given systemically, any healthy cell in the body exposed to the treatment drug may also accumulate therapy induced mutations. However, quantitative insights of treatment-induced mutations in normal tissues remain elusive. Here, we determine genome-wide mutation patterns in healthy adult stem cells (ASCs) of either the colon or the liver of 14 colorectal cancer patients after treatment with mutagenic anti-cancer therapies. Capecitabine/Oxaliplatin (CAPOX) induces 500-1000 mutations with a platinum-induced footprint in each colon adult stem cell. In contrast, capecitabine, which is metabolized to 5-fluorouracil (5-FU), effects strongly vary between and within patients with some colon ASCs accumulating up to 500 mutations from 5-FU, while most other colon ASCs show a complete absence of 5-FU mutagenesis. Finally, our results show that local radiation therapy induces deletions of &gt;5bp - 10kbp as well as structural rearrangements including reciprocal and multi-breakpoint variants in colon ASCs. Surprisingly and unlike colon ASCs, healthy liver ASCs of systemically treated colon cancer patients show no therapy-related mutations. Taken together, our results reveal that colon ASCs are particularly vulnerable to platinum-based therapies and to a lesser extent to treatments with 5-FU and may explain why platinum-based therapies, and not 5-FU, are associated with secondary malignancies. Consequently, while anticancer treatments are efficient in killing cancer cells, they increase the mutation burden in healthy cells explaining why treatment is an important risk factor for second cancers, but their mutational impact on healthy cells markedly differs between chemodrug and between tissue.","study_type":"Forensic or Paleo-genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-18T11:02:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006043","title":"Whole Exome Sequencing PPGL","description":"Whole exome sequencing (WES) libraries were prepared with the SureSelectXT Human All Exon V6+COSMIC target enrichment system (Agilent, 5190-9307) by following kit manufacturer`s instructions. 200 ng of genomic DNA from FFPE tumoral samples and 1 µg from FF or germline samples were used as starting material. SureSelectXT HS (Agilent, G9704A) and SureSelectXT2 (Agilent, G9621A) reagent kits were alternatively used for FFPE derived and good quality samples, respectively. DNAs were fragmented on a Covaris S2 sharing instrument based on initial sample’s integrity. Fragmented DNA samples were processed through subsequent enzymatic treatments of end-repair, dA-tailing, and ligation to Illumina's adapters. Adapter-ligated libraries were PCR amplified with Illumina PE primers and subsequently hybridized to SureSelect Oligo Capture Library Mix. Biotinylated hybrids were captured and the enriched fraction eluted. Libraries were completed by limited-cycle PCR with Illumina TruSeq primers and KAPA HiFi HotStart DNA pol (Roche KK2501). Sample-specific libraries were combined into equimolarly balanced pools and applied to Illumina flow cells for cluster generation. Sequencing was performed on either the Illumina HiSeq2500 or NovaSeq6000 in a paired-end 100bp reads mode to a median target coverage of ~200x and ~100x for tumors and germline, respectively.","abstract":"Whole exome sequencing (WES) libraries were prepared with the SureSelectXT Human All Exon V6+COSMIC target enrichment system (Agilent, 5190-9307) by following kit manufacturer`s instructions. 200 ng of genomic DNA from FFPE tumoral samples and 1 µg from FF or germline samples were used as starting material. SureSelectXT HS (Agilent, G9704A) and SureSelectXT2 (Agilent, G9621A) reagent kits were alternatively used for FFPE derived and good quality samples, respectively. DNAs were fragmented on a Covaris S2 sharing instrument based on initial sample’s integrity. Fragmented DNA samples were processed through subsequent enzymatic treatments of end-repair, dA-tailing, and ligation to Illumina's adapters. Adapter-ligated libraries were PCR amplified with Illumina PE primers and subsequently hybridized to SureSelect Oligo Capture Library Mix. Biotinylated hybrids were captured and the enriched fraction eluted. Libraries were completed by limited-cycle PCR with Illumina TruSeq primers and KAPA HiFi HotStart DNA pol (Roche KK2501). Sample-specific libraries were combined into equimolarly balanced pools and applied to Illumina flow cells for cluster generation. Sequencing was performed on either the Illumina HiSeq2500 or NovaSeq6000 in a paired-end 100bp reads mode to a median target coverage of ~200x and ~100x for tumors and germline, respectively.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-18T11:55:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006044","title":"Transcriptome Sequencing PPGL","description":"RNA library preparation of samples with RNA Integrity Number (RIN) &gt; 5.5 (median 7.1; range 5.6-8.9) was performed as described in the TruSeq Stranded mRNA Library Prep Kit (Illumina, RS-122-2101). Briefly, 0.7-1 µg total RNA PolyA+ fraction was purified and randomly fragmented, converted to double stranded cDNA and processed through subsequent enzymatic treatments of end-repair, dA-tailing, and ligation to adapters. Adapter-ligated library was completed by PCR with Illumina PE primers. The resulting purified cDNA library was applied to an Illumina flow cell for cluster generation and sequenced on an Illumina HiSeq2500 on a 51bp single-read format following manufacturer's protocols.\ncDNA libraries from FFPE tumors and low integrity RNA’s (RIN&lt;5.5) from FF tumors (median 2.4; range 1-5.5) but % of fragments &gt; 200 nucleotides higher than 20% (median 57.5; range 20-96) were prepared using QuantSeq 3’ mRNA-Seq Library Prep Kit FWD for Illumina (Lexogen, 015) with a UMI Second Strand Synthesis Module for QuantSeq FWD (Lexogen, 081), vendor’s protocol for low input/ low quality/ FFPE RNA using 200-500 ng of total RNA, according to availability, was used as starting material. PCR Add-on Kit for Illumina (Lexogen, 020) was used to adjust the library amplification number of cycles. Libraries were applied to an Illumina flow cell for cluster generation and sequenced on NovaSeq6000. \nImage analysis, per-cycle basecalling and quality score assignment was performed with Illumina Real Time Analysis software. Demultiplexing of BCL files to FASTQ format was performed with the bcl2fastq Software (Illumina).","abstract":"RNA library preparation of samples with RNA Integrity Number (RIN) &gt; 5.5 (median 7.1; range 5.6-8.9) was performed as described in the TruSeq Stranded mRNA Library Prep Kit (Illumina, RS-122-2101). Briefly, 0.7-1 µg total RNA PolyA+ fraction was purified and randomly fragmented, converted to double stranded cDNA and processed through subsequent enzymatic treatments of end-repair, dA-tailing, and ligation to adapters. Adapter-ligated library was completed by PCR with Illumina PE primers. The resulting purified cDNA library was applied to an Illumina flow cell for cluster generation and sequenced on an Illumina HiSeq2500 on a 51bp single-read format following manufacturer's protocols.\ncDNA libraries from FFPE tumors and low integrity RNA’s (RIN&lt;5.5) from FF tumors (median 2.4; range 1-5.5) but % of fragments &gt; 200 nucleotides higher than 20% (median 57.5; range 20-96) were prepared using QuantSeq 3’ mRNA-Seq Library Prep Kit FWD for Illumina (Lexogen, 015) with a UMI Second Strand Synthesis Module for QuantSeq FWD (Lexogen, 081), vendor’s protocol for low input/ low quality/ FFPE RNA using 200-500 ng of total RNA, according to availability, was used as starting material. PCR Add-on Kit for Illumina (Lexogen, 020) was used to adjust the library amplification number of cycles. Libraries were applied to an Illumina flow cell for cluster generation and sequenced on NovaSeq6000. \nImage analysis, per-cycle basecalling and quality score assignment was performed with Illumina Real Time Analysis software. Demultiplexing of BCL files to FASTQ format was performed with the bcl2fastq Software (Illumina).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-18T11:55:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006045","title":"Understanding_the_multicellular_dynamics_of_clear_cell_renal_cell_carcinoma___visium","description":"This study will reconstruct the single cellular phylogeny of tumour and immune cells in relation to both genomic, functional, and spatial location. 20 tumours in total will be studied, including non-progressing small renal masses, progressing small renal masses, relatively indolent larger tumours, and high risk tumour with metastatic sampling. We aim to:\n\nGenerate a focused, comprehensive phylogenetic characterisation of tumour cells\nUnderstand the dependencies of the cancer genome, transcriptome, tissue architecture and the single cellular micro-environment\nQuantify the single cellular composition and functional intra- and inter- tumoural heterogeneity\nDetermine the phylogeny of tumour associated lymphocytes and their relationship to neo-epitopes and the immune microenvironment\nInvestigate the mechanisms by which the tumour-normal interface constrains tumoural growth.","abstract":"This study will reconstruct the single cellular phylogeny of tumour and immune cells in relation to both genomic, functional, and spatial location. 20 tumours in total will be studied, including non-progressing small renal masses, progressing small renal masses, relatively indolent larger tumours, and high risk tumour with metastatic sampling. We aim to:\n\nGenerate a focused, comprehensive phylogenetic characterisation of tumour cells\nUnderstand the dependencies of the cancer genome, transcriptome, tissue architecture and the single cellular micro-environment\nQuantify the single cellular composition and functional intra- and inter- tumoural heterogeneity\nDetermine the phylogeny of tumour associated lymphocytes and their relationship to neo-epitopes and the immune microenvironment\nInvestigate the mechanisms by which the tumour-normal interface constrains tumoural growth.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-18T12:47:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006046","title":"HMW_DNA_extraction___Long_read_WGS_optimization","description":"The translational Cancer Genomics team are seeking support in identifying the most efficient, fast, simple and cost effective extraction kit from cell lines for long read sequencing. They have already identified and purchased three kits for this aim and require the testing of these, QC evaluation and finally evaluation on both Pacbio and ONT platforms. The regions of interest contain homopolymer stretches of AT which form secondary structures. It is possible (based on previous data) such structures pose a challenge for long read sequencing technologies to read through. It is also of significant interest to obtain methylation data during sequencing. The aim of this study is to compare different HMW DNA extraction methods and long-read sequencing data obtained by Pacbio and nanopore technologies.","abstract":"The aim of this study is to compare different HMW DNA extraction methods and long-read sequencing data obtained by Pacbio and nanopore technologies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006047","title":"HSC_population_dynamics___LEUK4_samples___methylseq_","description":"My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.\n\nThe four major questions I will address are:\n1.\tHow do age and aging affect normal human HSC dynamics in vivo?\n2.\tHow do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?\n3.\tIs response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?\n4.\tHow are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?","abstract":"Background\n\nSpontaneously occurring somatic mutations in single human haematopoietic stem cells (HSCs) provide a unique endogenous tag that can be tracked in peripheral blood to better understand native haematopoieisis in humans. Early exome studies in humans have revealed that mutations accumulate steadily throughout life, at the rate of approximately 1 mutation per genome per month per cell (Welch et al, 2012). A similar linear correlation between age and mutation burden has been observed in studies of haematological cancers (Alexandrov et al, 2015). Together, these studies suggest that somatic mutations in blood cells act as a molecular clock that could be used to track stem cell dynamics in human blood, providing insights into the total numbers of haematopoietic stem cells, changes in numbers over the human lifespan, patterns of self-renewal, and the effects perturbations and early driver mutations. This hypothesis is the basis of my research proposal.\n\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in four main groups of people:\n1.\tNormal healthy individuals over a range of ages\n2.\tIndividuals pre- and post-chemotherapy for localized colorectal cancer \n3.\tIndividuals with selenoprotein deficiency disorders, which cause elevated levels of reactive oxygen species\n4.\tIndividuals with clonal haematopoiesis (VAF &gt; 5%) identified through screening cohorts of healthy volunteers from the Cambridge Bioresource\n\nFor these experiments, the initial sample is 100 single cell-derived HSC colonies obtained from each individual (derived from peripheral blood in the majority of cases).  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the transcriptional level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 5x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. The ongoing analysis would be limited to heterozygous variants to avoid contaminating the data set with mutations that would have likely arisen in vitro. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified, using a published Bayesian method accounting for the possibility of missing mutations with the low coverage sequencing data (Jahn et al, 2016).  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived (Tataru et al, 2016 and Lan et al, 2015). In particular, expansions of population size at a given time are associated with an increased density of coalescences, while times of decreasing population size show a paucity of coalescences.  We will also be able to identify any variation in mutation rates and signatures over the human lifespan.  Baits to the somatic mutation ‘tags’ identified will be used to assess lineage contribution to peripheral blood granulocytes and monocytes.\n\nFor a subset of samples, we will undertake single cell RNA sequencing and single cell bisulphite sequencing on a number of cells from each colony.  This will allow us to investigate markers of senescence, active transcriptional programmes and levels of epigenetic heterogeneity within each individual.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006048","title":"To determine the genomic profiles of Ovarian carcinomas (UW cohort)","description":"Specific BRCA and immune configurations determine optimal response to platinum-based chemotherapy in triple negative breast and ovarian carcinomas (UW_OvCa_WGS)","abstract":"Specific BRCA and immune configurations determine optimal response to platinum-based chemotherapy in triple negative breast and ovarian carcinomas (UW_OvCa_WGS)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-18T19:16:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006049","title":"Single cell RNA sequencing of colorectal cancer patients (KUL3/KUL5)","description":"Libraries for scRNA-seq were generated using the Chromium Single Cell 3′ or 5′ library and Gel Bead &amp; Multiplex Kit from 10x Genomics. Aimed to profile 5000 cells per library (if sufficient cells were retained during dissociation).","abstract":"Libraries for scRNA-seq were generated using the Chromium Single Cell 3′ or 5′ library and Gel Bead &amp; Multiplex Kit from 10x Genomics. Aimed to profile 5000 cells per library (if sufficient cells were retained during dissociation).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-21T03:47:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006050","title":"CIRdb: Array genotype data","description":"The current inhabitants of the Canary Islands have a unique genetic makeup in the European diversity landscape due to the existence of African footprints from recent admixture events, especially of North African components (&gt;20%). The underrepresentation of non-Europeans in genetic studies and the sizable North African ancestry, which is nearly absent from all existing catalogs of worldwide genetic diversity, justify the need to develop CIRdb, a population-specific reference catalog of natural genetic variation in the Canary Islanders. Based on array genotyping of the selected unrelated donors and comparisons against available datasets from European, sub-Saharan, and North African populations, we illustrate the intermediate genetic differentiation of Canary Islanders between Europeans and North Africans and the existence of within-population differences that are likely driven by genetic isolation. In addition, here we describe the overall design and the methods that are being implemented to develop CIRdb.","abstract":"The current inhabitants of the Canary Islands have a unique genetic makeup in the European diversity landscape due to the existence of African footprints from recent admixture events, especially of North African components (&gt;20%). The underrepresentation of non-Europeans in genetic studies and the sizable North African ancestry, which is nearly absent from all existing catalogs of worldwide genetic diversity, justify the need to develop CIRdb, a population-specific reference catalog of natural genetic variation in the Canary Islanders. Based on array genotyping of the selected unrelated donors and comparisons against available datasets from European, sub-Saharan, and North African populations, we illustrate the intermediate genetic differentiation of Canary Islanders between Europeans and North Africans and the existence of within-population differences that are likely driven by genetic isolation. In addition, here we describe the overall design and the methods that are being implemented to develop CIRdb.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-21T11:05:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006051","title":"WGS of gastric cancer in the Japanese population  (81 gastric cancers of NCC)","description":"As a contribution to The International Cancer Genome Consortium Accelerating Research in Genomic Oncology (ICGC ARGO), whole-genome sequencing of 81 cases from Japanese gastric cancer with various histological subtypes has been conducted. \nThis study aims to reveal the landscape of structural variants (SV) in gastric cancer and analyze mutational and rearrangement signatures simultaneously","abstract":"As a contribution to The International Cancer Genome Consortium Accelerating Research in Genomic Oncology (ICGC ARGO), whole-genome sequencing of 81 cases from Japanese gastric cancer with various histological subtypes has been conducted. \nThis study aims to reveal the landscape of structural variants (SV) in gastric cancer and analyze mutational and rearrangement signatures simultaneously","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-22T03:01:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006052","title":"Microenvironment subtypes and association with tumor cell mutations and antigen expression in follicular lymphoma","description":"Follicular lymphoma (FL) is a B-cell lymphoma with a complex tumor microenvironment that is rich in non-malignant immune cells. We applied single-cell RNA-sequencing to characterize the immune microenvironment of FL. This provides a classification framework of the FL microenvironment, their association with FL genotypes and antigen presentation, and informs different potential immunotherapeutic strategies.","abstract":"Follicular lymphoma (FL) is a B-cell lymphoma with a complex tumor microenvironment that is rich in non-malignant immune cells. We applied single-cell RNA-sequencing to characterize the immune microenvironment of FL. This provides a classification framework of the FL microenvironment, their association with FL genotypes and antigen presentation, and informs different potential immunotherapeutic strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-22T09:48:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006053","title":"Insights from genome-wide data from Thailand and Laos","description":"We provide the first detailed insights into the genetic profiles of Thai/Lao ethnolinguistic groups, which should be helpful for reconstructing human genetic history in MSEA and selecting populations for participation in ongoing whole genome sequence and biomedical studies","abstract":"We provide the first detailed insights into the genetic profiles of Thai/Lao ethnolinguistic groups, which should be helpful for reconstructing human genetic history in MSEA and selecting populations for participation in ongoing whole genome sequence and biomedical studies","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-22T10:48:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006054","title":"A Phase Ib/II Study of Regorafenib and Paclitaxel in Beyond First-line Advanced Esophagogastric Carcinoma (REPEAT)","description":"Regorafenib showed promising results in gastric cancer. We aimed to assess the tolerability of regorafenib and paclitaxel in advanced esophagogastric cancer (EGC) patients refractory to first-line treatment and explore potential biomarkers.. We performed enzyme-linked \r\nimmunosorbent assay measurements of galectin-1, RNA sequencing, and shallow whole\u0002genome sequencing of metastatic tumor biopsies for biomarker analyses.","abstract":"Regorafenib showed promising results in gastric cancer. We aimed to assess the tolerability of regorafenib and paclitaxel in advanced esophagogastric cancer (EGC) patients refractory to first-line treatment and explore potential biomarkers.","study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-31T13:50:25.479888+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006055","title":"Oncogenic cooperation in a human de novo T-ALL model","description":"We previously modelled T-cell acute lymphoblastic leukemia (T-ALL) by over-expressing four oncogenes (activated NOTCH1, LMO2, TAL1, and BMI1) in healthy human umbilical cord blood cells through lentiviral transduction (Kusakabe et al, Nat Commun 10, 2913 (2019). https://doi.org/10.1038/s41467-019-10510-8). We have now tested individual effects of the four oncogenes by transducing human cells with all possible combinations of one, two, three, and four oncogenes. We also tested the effects of additional known T-ALL oncogenes including HOXA9, LYL1, MEF2C, NXK2.1, TLX1, and TLX3.\n\nIn addition to culture in vitro on OP9-DL1 feeders, we also injected transduced cells into immunodeficient NSG mice. We observed differing abilities of the various oncogene combinations to support growth in vitro and frank leukemia in vivo. This study includes RNA-seq data from samples of transduced cells cultured in vitro as well as cells harvested from clinically moribund mice after development of leukemia in vivo.","abstract":"We previously modelled T-cell acute lymphoblastic leukemia (T-ALL) by over-expressing four oncogenes (activated NOTCH1, LMO2, TAL1, and BMI1) in healthy human umbilical cord blood cells through lentiviral transduction (Kusakabe et al, Nat Commun 10, 2913 (2019). https://doi.org/10.1038/s41467-019-10510-8). We have now tested individual effects of the four oncogenes by transducing human cells with all possible combinations of one, two, three, and four oncogenes. We also tested the effects of additional known T-ALL oncogenes including HOXA9, LYL1, MEF2C, NXK2.1, TLX1, and TLX3.\n\nIn addition to culture in vitro on OP9-DL1 feeders, we also injected transduced cells into immunodeficient NSG mice. We observed differing abilities of the various oncogene combinations to support growth in vitro and frank leukemia in vivo. This study includes RNA-seq data from samples of transduced cells cultured in vitro as well as cells harvested from clinically moribund mice after development of leukemia in vivo.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-22T22:04:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006056","title":"Whole Genome sequencing of colorectal cancer patients (SG-BULK-3)","description":"The study was approved by the institutional review board of Singhealth (2018-2795). Ten 5-µm tissue sections were cut using standard microtomy techniques. Each collected cell population was then extracted using the allprep kit. Extracted material was then quantified using a Qubit fluorometer.","abstract":"The study was approved by the institutional review board of Singhealth (2018-2795). Ten 5-µm tissue sections were cut using standard microtomy techniques. Each collected cell population was then extracted using the allprep kit. Extracted material was then quantified using a Qubit fluorometer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-23T03:50:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006057","title":"The genomic landscape of pediatric renal cell carcinomas","description":"Pediatric renal cell carcinomas (RCC) differ from their adult counterparts not only in histologic subtypes, but also in clinical characteristics and outcome. However, the underlying biology is still largely unclear. For this reason, we performed whole-exome and transcriptome sequencing analyses on a cohort of 25 pediatric RCC patients with various histologic subtypes, including 10 MiT family translocation (MiT) and 10 papillary RCCs. In this cohort of pediatric RCC, we find only limited genomic overlap with adult RCC, even within the same histologic subtype. Recurrent somatic mutations in genes not previously reported in RCC were detected, such as in CCDC168, PLEKHA1, VWF, and MAP3K9. Our papillary pediatric RCCs, which represent the largest cohort to date with comprehensive molecular profiling in this age group, appeared as a distinct genomic subtype differing in terms of gene mutations and gene expression patterns not only from MiT-RCC, but also from their adult counterparts","abstract":"Pediatric renal cell carcinomas (RCC) differ from their adult counterparts not only in histologic subtypes, but also in clinical characteristics and outcome. However, the underlying biology is still largely unclear. For this reason, we performed whole-exome and transcriptome sequencing analyses on a cohort of 25 pediatric RCC patients with various histologic subtypes, including 10 MiT family translocation (MiT) and 10 papillary RCCs. In this cohort of pediatric RCC, we find only limited genomic overlap with adult RCC, even within the same histologic subtype. Recurrent somatic mutations in genes not previously reported in RCC were detected, such as in CCDC168, PLEKHA1, VWF, and MAP3K9. Our papillary pediatric RCCs, which represent the largest cohort to date with comprehensive molecular profiling in this age group, appeared as a distinct genomic subtype differing in terms of gene mutations and gene expression patterns not only from MiT-RCC, but also from their adult counterparts","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006058","title":"Analysis of recent shared ancestry in a familial cohort identifies coding and noncoding autism spectrum disorder variants","description":"Autism spectrum disorder (ASD) is a collection of neurodevelopmental disorders characterized by deficits in social communication and restricted, repetitive patterns of behavior or interests. ASD is highly heritable, but genetically and phenotypically heterogeneous, reducing the power to identify causative genes. We performed whole genome sequencing (WGS) in an ASD cohort of 68 individuals from 22 families enriched for recent shared ancestry. We identified an average of 3.07 million variants per genome, of which an average of 112,512 were rare. We mapped runs of homozygosity (ROHs) in affected individuals and found an average genomic homozygosity of 9.65%, consistent with expectations for multiple generations of consanguineous unions. We identified potentially pathogenic rare exonic or splice site variants in 12 known (including KMT2C, SCN1A, SPTBN1, SYNE1, ZNF292) and 12 candidate (including CHD5, GRB10, PPP1R13B) ASD genes. Furthermore, we annotated noncoding variants in ROHs with brain-specific regulatory elements and identified putative disease-causing variants within brain-specific promoters and enhancers for 5 known ASD and neurodevelopmental disease genes (ACTG1, AUTS2, CTNND2, CNTNAP4, SPTBN4). We also identified copy number variants in two known ASD and neurodevelopmental disease loci in two affected individuals. In total we identified potentially etiological variants in known ASD or neurodevelopmental disease genes for ~61% (14/23) of affected individuals. We combined WGS with homozygosity mapping and regulatory element annotations to identify candidate ASD variants. Our analyses add to the growing number of ASD genes and variants and emphasize the importance of leveraging recent shared ancestry to map disease variants in complex neurodevelopmental disorders.","abstract":"Autism spectrum disorder (ASD) is a collection of neurodevelopmental disorders characterized by deficits in social communication and restricted, repetitive patterns of behavior or interests. ASD is highly heritable, but genetically and phenotypically heterogeneous, reducing the power to identify causative genes. We performed whole genome sequencing (WGS) in an ASD cohort of 68 individuals from 22 families enriched for recent shared ancestry. We identified an average of 3.07 million variants per genome, of which an average of 112,512 were rare. We mapped runs of homozygosity (ROHs) in affected individuals and found an average genomic homozygosity of 9.65%, consistent with expectations for multiple generations of consanguineous unions. We identified potentially pathogenic rare exonic or splice site variants in 12 known (including KMT2C, SCN1A, SPTBN1, SYNE1, ZNF292) and 12 candidate (including CHD5, GRB10, PPP1R13B) ASD genes. Furthermore, we annotated noncoding variants in ROHs with brain-specific regulatory elements and identified putative disease-causing variants within brain-specific promoters and enhancers for 5 known ASD and neurodevelopmental disease genes (ACTG1, AUTS2, CTNND2, CNTNAP4, SPTBN4). We also identified copy number variants in two known ASD and neurodevelopmental disease loci in two affected individuals. In total we identified potentially etiological variants in known ASD or neurodevelopmental disease genes for ~61% (14/23) of affected individuals. We combined WGS with homozygosity mapping and regulatory element annotations to identify candidate ASD variants. Our analyses add to the growing number of ASD genes and variants and emphasize the importance of leveraging recent shared ancestry to map disease variants in complex neurodevelopmental disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-24T16:11:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006059","title":"Chromatin profiles classify castration-resistant prostate cancers suggesting therapeutic targets","description":"Untreated prostate cancers rely on androgen receptor (AR) signaling for growth and survival, forming the basis for the initial efficacy of androgen deprivation therapy (ADT). Yet, the disease can relapse and progress to a lethal stage termed castration-resistant prostate cancer (CRPC). Reactivation of AR signaling represents the most common driver of CRPC growth and next generation AR signaling inhibitors (ARSIs) are now used in combination with ADT as a first line therapy. However, ARSIs can result in selective pressure generating AR-independent tumors. The transition from AR-dependence frequently accompanies a change in phenotype resembling developmental trans-differentiation or ‘lineage plasticity’. Neuroendocrine prostate cancer, which lacks a defined pathologic classification, is the most studied type of lineage plasticity. However, most AR-null tumors do not exhibit neuroendocrine features and are classified as ‘double-negative prostate cancer’, the drivers of which are poorly defined. Lineage plasticity studies in CRPC are limited by the lack of genetically defined patient-derived models that recapitulate the disease spectrum. \nTo address this, we developed a biobank of organoids generated from patient biopsies to study the landscape of metastatic CRPC and allow for functional validation assays. Proteins called transcription factors (TFs) are drivers of tumor lineage plasticity. To identify the key TFs that drive the growth of AR-independent tumors, we integrated epigenetic and transcriptomic data generated from CRPC models. \nBy presenting a map of the chromatin accessibility and transcriptomic landscape of CRPC using a diverse biobank of organoids, PDXs and cell lines that recapitulate the heterogeneity of metastatic prostate cancer, we validate CRPC-AR and CRPC-NE subtypes and reveal two subtypes of AR-negative/low samples as well as their respective masterTFs. Additional analysis revealed a model in which YAP, TAZ, TEAD and AP-1 function together and drive oncogenic growth in CRPC-SCL samples. Overall, we show here how an approach to stratify CRPC patients into four subtypes using their transcriptomic signatures can potentially inform upon appropriate clinical decisions.","abstract":"Untreated prostate cancers rely on androgen receptor (AR) signaling for growth and survival, forming the basis for the initial efficacy of androgen deprivation therapy (ADT). Yet, the disease can relapse and progress to a lethal stage termed castration-resistant prostate cancer (CRPC). Reactivation of AR signaling represents the most common driver of CRPC growth and next generation AR signaling inhibitors (ARSIs) are now used in combination with ADT as a first line therapy. However, ARSIs can result in selective pressure generating AR-independent tumors. The transition from AR-dependence frequently accompanies a change in phenotype resembling developmental trans-differentiation or ‘lineage plasticity’. Neuroendocrine prostate cancer, which lacks a defined pathologic classification, is the most studied type of lineage plasticity. However, most AR-null tumors do not exhibit neuroendocrine features and are classified as ‘double-negative prostate cancer’, the drivers of which are poorly defined. Lineage plasticity studies in CRPC are limited by the lack of genetically defined patient-derived models that recapitulate the disease spectrum. \nTo address this, we developed a biobank of organoids generated from patient biopsies to study the landscape of metastatic CRPC and allow for functional validation assays. Proteins called transcription factors (TFs) are drivers of tumor lineage plasticity. To identify the key TFs that drive the growth of AR-independent tumors, we integrated epigenetic and transcriptomic data generated from CRPC models. \nBy presenting a map of the chromatin accessibility and transcriptomic landscape of CRPC using a diverse biobank of organoids, PDXs and cell lines that recapitulate the heterogeneity of metastatic prostate cancer, we validate CRPC-AR and CRPC-NE subtypes and reveal two subtypes of AR-negative/low samples as well as their respective masterTFs. Additional analysis revealed a model in which YAP, TAZ, TEAD and AP-1 function together and drive oncogenic growth in CRPC-SCL samples. Overall, we show here how an approach to stratify CRPC patients into four subtypes using their transcriptomic signatures can potentially inform upon appropriate clinical decisions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-24T21:59:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006060","title":"Genetics of non-syndromic idiopathic autism spectrum disorders in India","description":"The study explores the genetic architecture of patients diagnosed with non-syndromic autism spectrum disorders (according to the DSM-V criteria) in India. Patients were previously screened for aneuploidies using chromosomal G-banded karyotyping (at 500 band resolution) and Fragile-X using TP-PCR. Whole exome sequencing was performed on germline DNA from 100 idiopathic patients. Target enrichment was carried out using either Agilent SureSelect V6 or SureSelect Clinical Research Exome V2 kits. Pooled libraries were sequenced on Illumina HiSeq platform at an average coverage of 80-100x in 2x150bp configuration.","abstract":"The study explores the genetic architecture of patients diagnosed with non-syndromic autism spectrum disorders (according to the DSM-V criteria) in India. Patients were previously screened for aneuploidies using chromosomal G-banded karyotyping (at 500 band resolution) and Fragile-X using TP-PCR. Whole exome sequencing was performed on germline DNA from 100 idiopathic patients. Target enrichment was carried out using either Agilent SureSelect V6 or SureSelect Clinical Research Exome V2 kits. Pooled libraries were sequenced on Illumina HiSeq platform at an average coverage of 80-100x in 2x150bp configuration.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-25T12:36:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006061","title":"TMBur: A Distributable Tumor Mutation Burden Approach","description":null,"abstract":"We present a distributable tumor mutation burden (TMB) analysis suite, TMBur, to address the need for TMB estimate consistency in distributed projects that span jurisdictions. TMBur estimates are derived from whole genome sequencing (WGS) data, providing a measure of somatic mutation burden across the entire genome. TMBur reports a TMB estimate for coding space, protein-coding mutations, a pseudo-panel approach, and microsatellite instability values. We demonstrate the reproducibility of TMBur at multiple analysis centers and the clinical value of these estimates in predicting response to immune checkpoint inhibitors (ICIs).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006062","title":"A multi-center genome-wide association study for nasopharyngeal carcinoma","description":null,"abstract":"We performed a genome-wide association study (GWAS) for nasopharyngeal carcinoma (NPC), using a multi-center study (4083 NPC cases and 4811 controls). We derived a PRS from the GWAS and validated its performance in additional study samples.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-28T06:41:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006063","title":"Enhanced cortical neural stem cell identity through SMAD/WNT inhibition in human cerebral organoids facilitates emergence of outer radial glial cells","description":"Cerebral organoids exhibit broad regional heterogeneity accompanied by limited cortical cellular diversity despite the tremendous upsurge in derivation methods, suggesting inadequate patterning of early neural stem cells (NSCs). Here we show that a short and early dual-SMAD/WNT inhibition course is necessary and sufficient for establishing robust and lasting cortical organoid NSC identity, efficiently suppressing of non-cortical NSC fates, while other widely used methods are inconsistent in their cortical NSC specification capacity. Accordingly, this method selectively enriches for outer radial glia (oRG) NSCs, which cytoarchitecturally demarcate well-defined outer sub-ventricular (oSVZ)-like regions propagating from superiorly radially organized, apical cortical rosette NSCs. Finally, this method culminates in the emergence of molecularly distinct deep and upper cortical layer neurons, and reliably uncovers cortex-specific microcephaly defects. Thus, a short SMAD/WNT inhibition is critical for establishing a rich cortical cell repertoire that enables mirroring fundamental molecular and cytoarchitectural features of cortical development and meaningful disease modeling.","abstract":"Cerebral organoids exhibit broad regional heterogeneity accompanied by limited cortical cellular diversity despite the tremendous upsurge in derivation methods, suggesting inadequate patterning of early neural stem cells (NSCs). Here we show that a short and early dual-SMAD/WNT inhibition course is necessary and sufficient for establishing robust and lasting cortical organoid NSC identity, efficiently suppressing of non-cortical NSC fates, while other widely used methods are inconsistent in their cortical NSC specification capacity. Accordingly, this method selectively enriches for outer radial glia (oRG) NSCs, which cytoarchitecturally demarcate well-defined outer sub-ventricular (oSVZ)-like regions propagating from superiorly radially organized, apical cortical rosette NSCs. Finally, this method culminates in the emergence of molecularly distinct deep and upper cortical layer neurons, and reliably uncovers cortex-specific microcephaly defects. Thus, a short SMAD/WNT inhibition is critical for establishing a rich cortical cell repertoire that enables mirroring fundamental molecular and cytoarchitectural features of cortical development and meaningful disease modeling.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-28T07:30:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006064","title":"Targeted_NanoSeq_Heart","description":"Targeted NanoSeq in the heart from a number of donors, including donors with no past medical history of heart issues, as well as those with cardiomyopathy.","abstract":"Investigating the mutational landscape of a large number of heart samples.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006065","title":"11pcw_fetus_hdbr_15951_WGMS","description":"Whole genome methylation sequencing of the tissues of an 11 pcw fetus.","abstract":"Whole genome methylation sequencing of the tissues of an 11 pcw fetus.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006066","title":"Paediatric_CNS_tumour_autopsy_WGMS","description":"Whole genome methylation sequencing of normal and cancerous tissues from paediatric patients with diffuse midline gliomas.","abstract":"Whole genome methylation sequencing of normal and cancerous tissues from paediatric patients with diffuse midline gliomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006067","title":"Metagenomic sequencing of patient cerebrospinal fluid","description":null,"abstract":"Twenty-one cerebrospinal fluid samples, in which a known pathogen had been positively identified by available clinical techniques, were subjected to metagenomic DNA sequencing using massive parallel sequencing. Fourteen samples contained minute levels of Epstein-Barr virus. Pathogen sequences were detected in fifteen samples.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006068","title":"Integrative analysis of non-small cell lung cancer patient-derived xenografts identifies unique proteotypes associated with patient outcomes","description":"Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. Only a fraction of NSCLC harbour actionable driver mutations and there is an urgent need for patient-derived model systems that will enable the development of new targeted therapies. NSCLC and other cancers display profound proteome remodelling compared to normal tissue that is not predicted by DNA or RNA analyses. We generated  NSCLC patient-derived xenografts (PDXs) that recapitulate the histology and molecular features of primary NSCLC. Here, we completed whole exome sequencing on 122 NSCLC PDXs.","abstract":"Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. Only a fraction of NSCLC harbour actionable driver mutations and there is an urgent need for patient-derived model systems that will enable the development of new targeted therapies. NSCLC and other cancers display profound proteome remodelling compared to normal tissue that is not predicted by DNA or RNA analyses. We generated  NSCLC patient-derived xenografts (PDXs) that recapitulate the histology and molecular features of primary NSCLC. Here, we completed whole exome sequencing on 122 NSCLC PDXs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-28T17:07:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006069","title":"Genomic landscape of malignant peripheral nerve sheath tumor (MPNST)","description":"Neurofibromatosis type 1 (NF1) is the most common tumor predisposition syndrome, and is associated with an aggressive soft-tissue sarcoma, malignant peripheral nerve sheath tumours (MPNSTs), the greatest cause of morbidity and mortality in people with NF1. The only potentially curative therapy involves surgery which is not always possible. Even therapy with curative intent is associated with poor overall survival for both sporadic and NF1-related MPNSTs. The development of novel therapies has been largely hindered by a lack of understanding of the molecular events underpinning MPNST pathogenesis. This is a comprehensive multi-omic study of MPNST evolution based on whole genome sequencing and transcriptomic data.","abstract":"Neurofibromatosis type 1 (NF1) is the most common tumor predisposition syndrome, and is associated with an aggressive soft-tissue sarcoma, malignant peripheral nerve sheath tumours (MPNSTs), the greatest cause of morbidity and mortality in people with NF1. The only potentially curative therapy involves surgery which is not always possible. Even therapy with curative intent is associated with poor overall survival for both sporadic and NF1-related MPNSTs. The development of novel therapies has been largely hindered by a lack of understanding of the molecular events underpinning MPNST pathogenesis. This is a comprehensive multi-omic study of MPNST evolution based on whole genome sequencing and transcriptomic data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-02-28T19:25:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006070","title":"Exome_sequencing_of_South_African_tumours","description":"We wish to perform whole exome sequencing on oesophageal SCC tumours from South African patients.  South African has a particularly high incidence of oesophageal SCC and we wish to try and understand the underlying cause of this.","abstract":"We wish to perform whole exome sequencing on oesophageal SCC tumours from South African patients.  South African has a particularly high incidence of oesophageal SCC and we wish to try and understand the underlying cause of this.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006071","title":"Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity","description":null,"abstract":"Investigation of prostate cancer landscape through spatial transcriptomics.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006072","title":"Clear cell sarcoma sequencing data","description":"This study shares DNA and RNA sequencing data from Clear cell sarcoma patients","abstract":"This study shares DNA and RNA sequencing data from Clear cell sarcoma patients","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-01T17:23:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006073","title":"Genomic and transcriptomic analysis of baseline PDAC patients' tumors from the OXIRI phase 1b clinical trial","description":"This study was aimed at investigating the genomic and transcriptomic features associated with response to the OXIRI regimen (oxaliplatin, irinotecan, capecitabine) in pancreatic ductal adenocarcinoma (PDAC) tumors. We performed whole-exome sequencing (WES) and RNA sequencing (RNA-seq) on baseline tumor samples obtained from 8 patients recruited in the OXIRI phase 1b clinical trial (NCT02368860).","abstract":"This study was aimed at investigating the genomic and transcriptomic features associated with response to the OXIRI regimen (oxaliplatin, irinotecan, capecitabine) in pancreatic ductal adenocarcinoma (PDAC) tumors. We performed whole-exome sequencing (WES) and RNA sequencing (RNA-seq) on baseline tumor samples obtained from 8 patients recruited in the OXIRI phase 1b clinical trial (NCT02368860).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-02T02:04:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006074","title":"Thrombosis related with COVID-19 in 100 spanish subject","description":null,"abstract":"The study of the genetic basis of the risk of thrombosis to stratify COVID-19 patients","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006075","title":"RNAsequencing of large collection of metastatic colorectal cancer xenografts","description":null,"abstract":"long story short","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006076","title":"HSC_population_dynamics_in_perturbation___76F1_samples","description":"The aim of this project is to characterise how the systemic environment shapes the clonal landscape in \nadult humans and how perturbations affect this landscape. We are collecting longitudinal samples from \npatients before and after chemotherapy, in order to perform whole genome sequencing on their HSCs \nand, using patterns of shared and unique mutations, construct a phylogenetic tree of each patient’s \nHSCs. This will allow us to interrogate how clonal composition changes in response to chemotherapy, \nshedding insight into the fitness of mutations with respect to age and treatment.\nThe questions I want to answer: \n1. Are mutations that gave some HSCs an advantage, which resulted in their clonal expansion, still \nadvantageous in the new environment? Does chemotherapy favour some mutations over others? \n2. How do chemotherapies of different intensities affect the clonal landscape of HSCs? \n3. How does ageing affect the ability of the hematopoietic system to recover after chemotherapy? Are \nany clinical variables associated with improved recovery? \n4. Does the population of HSCs remain unchanged? \n5. How do different chemotherapies contribute to mutagenesis of HSCs?","abstract":"Background \nWith age, somatic mutations accumulate in normal dividing cells, including hematopoietic stem cells \n(HSCs). It appears that some mutations provide HSCs with a fitness advantage, allowing their mutant \ndaughter blood cells to disproportionately expand (Jaiswal &amp; Ebert, 2019). The phenomenon is termed \nclonal hematopoiesis (CH) and it is associated with ageing as well as hematologic malignancies, \ncardiovascular disease and all-cause mortality (Genovese et al., 2014; Jaiswal &amp; Ebert, 2019). \nPreliminary evidence suggests that after a perturbation such as cancer therapy, the composition of \nclones, which dominate the hematopoietic system, changes (Bolton, 2020). However, the studies \ncarried out until now have analysed CH at the population level, but little is known about the process at \nan individual level. Moreover, no study until now has addressed how perturbations of the systemic \nenvironment affect the clonal composition of blood at the single-cell level. \nCohort Description\nWe will take peripheral blood samples from 1 normal individual and 14 patients undergoing \nchemotherapy for the treatment of lymphoma with confirmed absence of bone marrow involvement. The \nchemotherapy-treated cohort will consist of 4 younger adults (aged under 55 years) and 8 older adults \n(aged over 70 years) who will all be receiving R- CHOP for treating diffuse large B-cell lymphoma as \nwell as 2 younger adults who are receiving a more intensive chemotherapy regimen such as BEACOPP \nor ABVD for the treatment of Hodgkin’s lymphoma. The described design will allow us to compare the \nresponse of the hematopoietic system at different ages to chemotherapy of different intensities, as well \nas provide a control to ensure longitudinal changes are not observed in normal, healthy individuals.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006077","title":"HSC_population_dynamics_in_perturbation___75M1_samples","description":"The aim of this project is to characterise how the systemic environment shapes the clonal landscape in \nadult humans and how perturbations affect this landscape. We are collecting longitudinal samples from \npatients before and after chemotherapy, in order to perform whole genome sequencing on their HSCs \nand, using patterns of shared and unique mutations, construct a phylogenetic tree of each patient’s \nHSCs. This will allow us to interrogate how clonal composition changes in response to chemotherapy, \nshedding insight into the fitness of mutations with respect to age and treatment.\nThe questions I want to answer: \n1. Are mutations that gave some HSCs an advantage, which resulted in their clonal expansion, still \nadvantageous in the new environment? Does chemotherapy favour some mutations over others? \n2. How do chemotherapies of different intensities affect the clonal landscape of HSCs? \n3. How does ageing affect the ability of the hematopoietic system to recover after chemotherapy? Are \nany clinical variables associated with improved recovery? \n4. Does the population of HSCs remain unchanged? \n5. How do different chemotherapies contribute to mutagenesis of HSCs?","abstract":"Background \nWith age, somatic mutations accumulate in normal dividing cells, including hematopoietic stem cells \n(HSCs). It appears that some mutations provide HSCs with a fitness advantage, allowing their mutant \ndaughter blood cells to disproportionately expand (Jaiswal &amp; Ebert, 2019). The phenomenon is termed \nclonal hematopoiesis (CH) and it is associated with ageing as well as hematologic malignancies, \ncardiovascular disease and all-cause mortality (Genovese et al., 2014; Jaiswal &amp; Ebert, 2019). \nPreliminary evidence suggests that after a perturbation such as cancer therapy, the composition of \nclones, which dominate the hematopoietic system, changes (Bolton, 2020). However, the studies \ncarried out until now have analysed CH at the population level, but little is known about the process at \nan individual level. Moreover, no study until now has addressed how perturbations of the systemic \nenvironment affect the clonal composition of blood at the single-cell level. \nCohort Description\nWe will take peripheral blood samples from 1 normal individual and 14 patients undergoing \nchemotherapy for the treatment of lymphoma with confirmed absence of bone marrow involvement. The \nchemotherapy-treated cohort will consist of 4 younger adults (aged under 55 years) and 8 older adults \n(aged over 70 years) who will all be receiving R- CHOP for treating diffuse large B-cell lymphoma as \nwell as 2 younger adults who are receiving a more intensive chemotherapy regimen such as BEACOPP \nor ABVD for the treatment of Hodgkin’s lymphoma. The described design will allow us to compare the \nresponse of the hematopoietic system at different ages to chemotherapy of different intensities, as well \nas provide a control to ensure longitudinal changes are not observed in normal, healthy individuals","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006078","title":"HSC_population_dynamics_in_perturbation___44M1_samples","description":"The aim of this project is to characterise how the systemic environment shapes the clonal landscape in \nadult humans and how perturbations affect this landscape. We are collecting longitudinal samples from \npatients before and after chemotherapy, in order to perform whole genome sequencing on their HSCs \nand, using patterns of shared and unique mutations, construct a phylogenetic tree of each patient’s \nHSCs. This will allow us to interrogate how clonal composition changes in response to chemotherapy, \nshedding insight into the fitness of mutations with respect to age and treatment.\nThe questions I want to answer: \n1. Are mutations that gave some HSCs an advantage, which resulted in their clonal expansion, still \nadvantageous in the new environment? Does chemotherapy favour some mutations over others? \n2. How do chemotherapies of different intensities affect the clonal landscape of HSCs? \n3. How does ageing affect the ability of the hematopoietic system to recover after chemotherapy? Are \nany clinical variables associated with improved recovery? \n4. Does the population of HSCs remain unchanged? \n5. How do different chemotherapies contribute to mutagenesis of HSCs?","abstract":"Background \nWith age, somatic mutations accumulate in normal dividing cells, including hematopoietic stem cells \n(HSCs). It appears that some mutations provide HSCs with a fitness advantage, allowing their mutant \ndaughter blood cells to disproportionately expand (Jaiswal &amp; Ebert, 2019). The phenomenon is termed \nclonal hematopoiesis (CH) and it is associated with ageing as well as hematologic malignancies, \ncardiovascular disease and all-cause mortality (Genovese et al., 2014; Jaiswal &amp; Ebert, 2019). \nPreliminary evidence suggests that after a perturbation such as cancer therapy, the composition of \nclones, which dominate the hematopoietic system, changes (Bolton, 2020). However, the studies \ncarried out until now have analysed CH at the population level, but little is known about the process at \nan individual level. Moreover, no study until now has addressed how perturbations of the systemic \nenvironment affect the clonal composition of blood at the single-cell level. \nCohort Description\nWe will take peripheral blood samples from 1 normal individual and 14 patients undergoing \nchemotherapy for the treatment of lymphoma with confirmed absence of bone marrow involvement. The \nchemotherapy-treated cohort will consist of 4 younger adults (aged under 55 years) and 8 older adults \n(aged over 70 years) who will all be receiving R- CHOP for treating diffuse large B-cell lymphoma as \nwell as 2 younger adults who are receiving a more intensive chemotherapy regimen such as BEACOPP \nor ABVD for the treatment of Hodgkin’s lymphoma. The described design will allow us to compare the \nresponse of the hematopoietic system at different ages to chemotherapy of different intensities, as well \nas provide a control to ensure longitudinal changes are not observed in normal, healthy individuals.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006079","title":"Comprehensive Molecular Profiling Identifies Features of Disease Resistance to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer","description":null,"abstract":"Comprehensive Molecular Profiling Identifies Features of Disease Resistance to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006080","title":"Cancer sequencing study","description":null,"abstract":"test","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006081","title":"Dummy study","description":null,"abstract":"Publication extract","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006082","title":"cancer test study","description":null,"abstract":"cancer test study","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006083","title":"RNAseq analysis on metastatic Colorectal Cancer xenografts","description":null,"abstract":"Bank of metastatic colorectal cancer (mCRC) of Patient Derived Xenografts (PDXs)","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006084","title":"HCA_Skin_Disease_HS_WSSS_RNA_NCL","description":"WSSS Deep dive of diseased human adult skin","abstract":"WSSS Deep dive of diseased human adult skin - Hidradenitis Suppurativa","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006085","title":"To determine the genomic profiles of Triple Negative Breast Cancers (COH cohort)","description":"Specific BRCA and immune configurations determine optimal response to platinum-based chemotherapy in triple negative breast and ovarian carcinomas (COH_TNBC_WGS)","abstract":"Specific BRCA and immune configurations determine optimal response to platinum-based chemotherapy in triple negative breast and ovarian carcinomas (COH_TNBC_WGS)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-03T13:30:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006086","title":"HCA_Gut_Disease_Crohns_Helmsley_RNA","description":"Single cell gut atlas in Crohn’s Disease","abstract":"This projects encompasses paediatric patient samples from healthy children and those diagnosed with Crohn’s Disease. We will perform scRNAseq on terminal ileum and colon (sigmoid or ascending) biopsies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006087","title":"HCA_Gut_Disease_Crohns_Helmsley_Organoid_RNA","description":"Single cell of intestinal organoids in health and Crohn’s Disease","abstract":"This projects encompasses organoids derived from paediatric patient samples from healthy children and those diagnosed with Crohn’s Disease. We will perform scRNAseq on organoids in different stimulation conditions.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006088","title":"The evolutionary dynamics of human colorectal cancer using single-gland spatial multi-omic profiling of DNA, RNA and chromatin.","description":null,"abstract":"Deciphering the mechanisms of colorectal cancer growth, progression and dissemination in each individual patient,","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-03T19:19:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006089","title":"Genomic History of Siberia","description":null,"abstract":"The aim of this study was to provide for a better understanding of the genetic interactions between Siberian peoples, with a focus on disentangling shared ancestry from prehistoric migrations and contact.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-03T21:02:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006090","title":"The Spatial Heterogeneity in Multiple Myeloma - from the Subclonal Architecture to the Immune Microenvironment (partly hipo_K08K)","description":"Multiple myeloma (MM) cells show pronounced heterogeneity not only within a given patient but also between spatially separated tumor loci in the bone marrow. Understanding this spatial heterogeneity is emerging as a critical challenge for the successful treatment of the disease. Yet, our understanding of spatial differences in the subclonal architecture, molecular signatures and interactions with the tumor microenvironment remains very limited.\nTo address this shortcoming, we performed bulk and single-cell multi-region sequencing, including random bone marrow samples from the iliac crest and paired imaging-guided focal lesion specimens from 15 newly diagnosed MM patients. We found a median of 5 subclones per patient and unique subclones in focal lesions. Central features of spatial heterogeneity included a consistent down-regulation of the chemoattractant cytokines CXCL7 and CXCL12 in focal lesion tumor cells as well as a significant depletion of macrophages in the focal lesion microenvironment. In contrast, a site-specific expansion of T-cell clones was not detected in focal lesions. In conclusion, our results demonstrate the relevance of considering spatial heterogeneity with potential implications for immunotherapies and molecular studies analyzing the role of gene signatures and MM-microenvironment interactions in disease progression.","abstract":"Multiple myeloma (MM) cells show pronounced heterogeneity not only within a given patient but also between spatially separated tumor loci in the bone marrow. Understanding this spatial heterogeneity is emerging as a critical challenge for the successful treatment of the disease. Yet, our understanding of spatial differences in the subclonal architecture, molecular signatures and interactions with the tumor microenvironment remains very limited.\nTo address this shortcoming, we performed bulk and single-cell multi-region sequencing, including random bone marrow samples from the iliac crest and paired imaging-guided focal lesion specimens from 15 newly diagnosed MM patients. We found a median of 5 subclones per patient and unique subclones in focal lesions. Central features of spatial heterogeneity included a consistent down-regulation of the chemoattractant cytokines CXCL7 and CXCL12 in focal lesion tumor cells as well as a significant depletion of macrophages in the focal lesion microenvironment. In contrast, a site-specific expansion of T-cell clones was not detected in focal lesions. In conclusion, our results demonstrate the relevance of considering spatial heterogeneity with potential implications for immunotherapies and molecular studies analyzing the role of gene signatures and MM-microenvironment interactions in disease progression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-03T23:11:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006091","title":"Res1_H23_exp1_MC_04_03_22","description":"1 sample is pure plasmid DNA and 8 samples are cell pellets for genomic DNA extraction.\nCRISPR PCR1 and PCR2 indexing - Please use standard Kozuke primers.","abstract":"1 sample is pure plasmid DNA and 8 samples are cell pellets for genomic DNA extraction.\nCRISPR PCR1 and PCR2 indexing - Please use standard Kozuke primers.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-04T08:58:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006092","title":"Res1_HT29_exp1_MC_02_03_22","description":"1 sample is pure plasmid DNA and 10 samples are cell pellets for genomic DNA extraction.\nCRISPR PCR1 and PCR2 indexing - Please use standard Kozuke primers.","abstract":"1 sample is pure plasmid DNA and 10 samples are cell pellets for genomic DNA extraction.\nCRISPR PCR1 and PCR2 indexing - Please use standard Kozuke primers.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-04T09:05:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006093","title":"Res1_HT29_exp2_MC_03_03_22","description":"1 sample is pure plasmid DNA and 10 samples are cell pellets for genomic DNA extraction.\nCRISPR PCR1 and PCR2 indexing - Please use standard Kozuke primers.","abstract":"1 sample is pure plasmid DNA and 10 samples are cell pellets for genomic DNA extraction.\nCRISPR PCR1 and PCR2 indexing - Please use standard Kozuke primers.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-04T09:09:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006094","title":"Hodgkin_project___mutational_burden_of_chemotherapy_in_normal_blood","description":"This study aims to further investigate the mutational burden induced by chemotherapy in the normal stem and progenitor cell of individuals treated for Hodgkin's lymphoma. Single cell derived progenitor colonies have been grown and DNA extracted. 5-10 colonies from 12 individuals exposed to either ABVD, EscBEACOPP or EscBEACOPDac will undergo whole genome sequencing to address the question of the extent of mutational impact of these different regimens.","abstract":"This study aims to further investigate the mutational burden induced by chemotherapy in the normal stem and progenitor cell of individuals treated for Hodgkin's lymphoma. Single cell derived progenitor colonies have been grown and DNA extracted. 5-10 colonies from 12 individuals exposed to either ABVD, EscBEACOPP or EscBEACOPDac will undergo whole genome sequencing to address the question of the extent of mutational impact of these different regimens.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006095","title":"Genotyping study","description":null,"abstract":"primary and relapsed neurob","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006096","title":"Tumour evolvability metrics predict recurrence in advanced localised prostate cancer (tumour data)","description":null,"abstract":"There is a need for quantitative measurements of evolutionary metrics in controlled clinical trials with long term follow-up information. This is particularly true in advanced localised prostate cancer, which can recur more than a decade after diagnosis. Here we mapped genomic intra-tumour heterogeneity in 642 tumour samples from 114 patients who took part in the IMRT and DELINEATE clinical trials, for which full clinical information and 12y median follow-up was available. We concomitantly assessed phenotypic (morphological) heterogeneity using Deep Learning in 1,923 histological sections from 250 IMRT patients (fully overlapping with the genetic set). This study shows that combining genomics with AI-aided histopathology in clinical trials leads to novel clinical biomarkers.\nThis EGA repository contains data produced from tumour samples using low coverage whole genome sequencing and a prostate cancer specific gene panel data following compression of unique molecular identifiers.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-04T14:48:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006097","title":"test","description":null,"abstract":"test","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006098","title":"Tumour evolvability metrics predict recurrence in advanced localised prostate cancer (normal data)","description":null,"abstract":"There is a need for quantitative measurements of evolutionary metrics in controlled clinical trials with long term follow-up information. This is particularly true in advanced localised prostate cancer, which can recur more than a decade after diagnosis. Here we mapped genomic intra-tumour heterogeneity in 642 tumour samples from 114 patients who took part in the IMRT and DELINEATE clinical trials, for which full clinical information and 12y median follow-up was available. We concomitantly assessed phenotypic (morphological) heterogeneity using Deep Learning in 1,923 histological sections from 250 IMRT patients (fully overlapping with the genetic set). This study shows that combining genomics with AI-aided histopathology in clinical trials leads to novel clinical biomarkers.\nThis EGA repository contains data produced from tumour samples using low coverage whole genome sequencing and a prostate cancer specific gene panel data following compression of unique molecular identifiers.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-04T14:50:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006099","title":"First test submission","description":null,"abstract":"5-10 sentences to describe the study.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006100","title":"First in vivo investigation of the impact of PARP inhibition with rucaparib alone and in combination with atezolizumab: results of the phase Ib COUPLET clinical study in advanced gynecologic and triple-negative breast cancers","description":null,"abstract":"We explored the combination of the PARPi rucaparib and the anti-PD-L1 monoclonal antibody atezolizumab in biomarker-selected populations of patients with advanced gynecologic cancers or TNBC. The study evaluated the safety profile and potential pharmacokinetic (PK) interactions of the combination. Transcriptome profiling and in situ analysis of pre-treatment, rucaprib run-in and post rucaparib plus atezolizumab combination tissues revealed interesting changes in DNA damaging repair, cell cycle, cell death, and tumor immune microenvironment.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006101","title":"Whole Genome sequencing of colorectal cancer patients (SG-BULK-4)","description":"The study was approved by the institutional review board of Singhealth (2018-2795). Ten 5-µm tissue sections were cut using standard microtomy techniques. Each collected cell population was then extracted using the allprep kit. Extracted material was then quantified using a Qubit fluorometer.","abstract":"The study was approved by the institutional review board of Singhealth (2018-2795). Ten 5-µm tissue sections were cut using standard microtomy techniques. Each collected cell population was then extracted using the allprep kit. Extracted material was then quantified using a Qubit fluorometer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-05T05:55:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006102","title":"A genome-wide association study for nasopharyngeal carcinoma in Hong Kong population","description":null,"abstract":"We performed a genome-wide association study (GWAS) for nasopharyngeal carcinoma (NPC) in Hong Kong population (423 NPC cases and 573 controls). We derived a PRS from the GWAS and validate its performance in additional study samples.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-06T08:18:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006103","title":"High-throughput telomere length measurement at nucleotide resolution using the PacBio high fidelity sequencing platform","description":"Telomeres are specialized nucleoprotein structures at the ends of linear chromosomes that are essential for the stability as well as the complete replication of the human genome. The progressive shortening of steady-state telomere length in normal human somatic cells is a promising biomarker for age-associated diseases. However, there remain substantial challenges in quantifying telomere length in clinics and research laboratories due to the lack of accurate and high-throughput telomere length measurement method. Here, we describe a novel workflow to capture and analyze telomeres accurately at the single-nucleotide resolution. By using newly designed telobaits that are complementary to the single-stranded G-rich 3’ telomeric overhangs, we can specifically and efficiently capture full-length telomeres and subject them to single-molecule real-time (SMRT) sequencing. We show that the telomere length can be measured at nucleotide resolution using the PacBio high fidelity (HiFi) sequencing platform, which provides the necessary accuracy and throughput to uncover the steady-state telomere length distribution in human culture cell lines as well as clinical patient samples. This new method is a valuable tool not only in population-wide epidemiology studies but also for the longitudinal assessment of telomere attrition in individuals. Our results also reveal the extreme heterogeneity of telomeric variant sequences (TVSs) that is dispersed throughout the telomere repeat region. Importantly, the unique distribution pattern and sequence of TVSs in individuals may be used as a fingerprint for sample identification. In addition, the presence of TVSs disrupts the continuity of the canonical (5’-TTAGGG-3’)n telomere repeats, which could affect the binding of shelterin complexes at the chromosomal ends. Therefore, TVSs may act as a form of genetic polymorphisms that impairs telomere protection. Together with the absolute telomere length in each individual, TVSs may have profound implications in human aging and diseases.","abstract":"Telomeres are specialized nucleoprotein structures at the ends of linear chromosomes that are essential for the stability as well as the complete replication of the human genome. The progressive shortening of steady-state telomere length in normal human somatic cells is a promising biomarker for age-associated diseases. However, there remain substantial challenges in quantifying telomere length in clinics and research laboratories due to the lack of accurate and high-throughput telomere length measurement method. Here, we describe a novel workflow to capture and analyze telomeres accurately at the single-nucleotide resolution. By using newly designed telobaits that are complementary to the single-stranded G-rich 3’ telomeric overhangs, we can specifically and efficiently capture full-length telomeres and subject them to single-molecule real-time (SMRT) sequencing. We show that the telomere length can be measured at nucleotide resolution using the PacBio high fidelity (HiFi) sequencing platform, which provides the necessary accuracy and throughput to uncover the steady-state telomere length distribution in human culture cell lines as well as clinical patient samples. This new method is a valuable tool not only in population-wide epidemiology studies but also for the longitudinal assessment of telomere attrition in individuals. Our results also reveal the extreme heterogeneity of telomeric variant sequences (TVSs) that is dispersed throughout the telomere repeat region. Importantly, the unique distribution pattern and sequence of TVSs in individuals may be used as a fingerprint for sample identification. In addition, the presence of TVSs disrupts the continuity of the canonical (5’-TTAGGG-3’)n telomere repeats, which could affect the binding of shelterin complexes at the chromosomal ends. Therefore, TVSs may act as a form of genetic polymorphisms that impairs telomere protection. Together with the absolute telomere length in each individual, TVSs may have profound implications in human aging and diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-07T03:54:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006104","title":"HCA_Bone_Foetal_WSSS_Dev_RNA","description":"This study involves mapping the development of the fetal skeleton, in order to understand the process of ossification and skeletal maturation throughout the first and second trimester.","abstract":"There is limited literature that examines the development of the fetal skeletal system in the fetus at the single-cell resolution. Similarly, there is a lack of deep appreciation of this process in the second trimester of fetal development, when woven bone from intramembranous and endochondral begins to remodel and form definitively. We aim to collect normal first and second trimester fetal bone samples, throughout the skeleton. We will analyze bone populations, including the cranium, skull base, long bones and intact joints connecting bones at the spine, hips and knee. We will then use single-nuclei RNA and ATAC sequencing to map the development of these populations, and key steps that govern their identities throughout the second trimester. The proposed comparative analysis of ossification across anatomical regions will provide a deeper understanding of skeletal maturation and form a basis for understanding cell-type compositional and epigenomic perturbations in disease and in development, aging and adulthood.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006105","title":"Profiling of 27 type 2 diabetes GWAS loci using next-generation (NG) capture C in a human beta-cell model","description":"Most type 2 diabetes association signals are due to variants that impact gene regulation but identifying the genes they impact is challenging. We generated interaction profiles at 27 T2D GWAS loci using next-generation (NG) capture C in a human beta-cell model ( EndoC-betaH1) and contrasted our maps with public Hi-C/promoter capture Hi-C maps in EndoC-betaH1 cells or human islets.","abstract":"Most type 2 diabetes association signals are due to variants that impact gene regulation but identifying the genes they impact is challenging. We generated interaction profiles at 27 T2D GWAS loci using next-generation (NG) capture C in a human beta-cell model ( EndoC-betaH1) and contrasted our maps with public Hi-C/promoter capture Hi-C maps in EndoC-betaH1 cells or human islets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-08T01:08:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006106","title":"Single cell analyses of transcriptome and epigenome in neuroblastoma infiltrated bone marrow","description":"We report transcriptional and genome-wide ATAC-seq analyses at single cell resolution of 16 bone marrow samples with and without neuroblastoma infiltration. Our samples span across several neuroblastoma models, including MYCN amplified, ATRX mutated, and sporadic (lacking either alteration).","abstract":"We report transcriptional and genome-wide ATAC-seq analyses at single cell resolution of 16 bone marrow samples with and without neuroblastoma infiltration. Our samples span across several neuroblastoma models, including MYCN amplified, ATRX mutated, and sporadic (lacking either alteration).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-08T09:34:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006107","title":"Adult B-precursor acute lymphoblastic leukemia transcriptomes","description":"Bone marrow or peripheral blood samples were collected of adult patients at first diagnosis of B-precursor acute lymphoblastic leukemia. RNA was isolated from mononuclear cells and subjected to mRNA library prep using Poly-A selection and sequencing on a NovaSeq 6000 system. Obtained gene expression profiles and gene fusion calls were used to allocate samples to molecular disease subtypes.","abstract":"Bone marrow or peripheral blood samples were collected of adult patients at first diagnosis of B-precursor acute lymphoblastic leukemia. RNA was isolated from mononuclear cells and subjected to mRNA library prep using Poly-A selection and sequencing on a NovaSeq 6000 system. Obtained gene expression profiles and gene fusion calls were used to allocate samples to molecular disease subtypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-09T06:28:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006108","title":"Exploring_the_influence_of_mutagens_on_the_transcriptome_in_single_cell_derived_lung_colonies_RNA","description":"This study aims to characterize the transcriptomic landscape of single-cell derived colonies from lung tissue of normal bronchial epithelial cells from patients with various smoking histories upon influence of selected mutagens. Single-cell derived colonies have been created from patients that underwent broncoscopy, as described in the work published by Yoshida and colleagues (https://www.nature.com/articles/s41586-020-1961-1/). Here, we will follow-up on this work by characterizing colonies with near-normal mutation burden that have been exposed to selected mutagens over a certain period of time in order to determine the landscape of transcriptomic alterations in these cells","abstract":"This study aims to characterize the transcriptomic landscape of single-cell derived colonies from lung tissue of normal bronchial epithelial cells from patients with various smoking histories upon influence of selected mutagens. Single-cell derived colonies have been created from patients that underwent broncoscopy, as described in the work published by Yoshida and colleagues (https://www.nature.com/articles/s41586-020-1961-1/). Here, we will follow-up on this work by characterizing colonies with near-normal mutation burden that have been exposed to selected mutagens over a certain period of time in order to determine the landscape of transcriptomic alterations in these cells.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006109","title":"Exploring_the_influence_of_mutagens_on_the_genome_in_single_cell_derived_lung_colonies_Duplex","description":"This study aims to characterize the transcriptomic landscape of single-cell derived colonies from lung tissue of normal bronchial epithelial cells from patients with various smoking histories upon influence of selected mutagens. Single-cell derived colonies have been created from patients that underwent broncoscopy, as described in the work published by Yoshida and colleagues (https://www.nature.com/articles/s41586-020-1961-1/). Here, we will follow-up on this work by characterizing colonies with near-normal mutation burden that have been exposed to selected mutagens over a certain period of time in order to determine the landscape of genomic alterations in these cells","abstract":"This study aims to characterize the transcriptomic landscape of single-cell derived colonies from lung tissue of normal bronchial epithelial cells from patients with various smoking histories upon influence of selected mutagens. Single-cell derived colonies have been created from patients that underwent broncoscopy, as described in the work published by Yoshida and colleagues (https://www.nature.com/articles/s41586-020-1961-1/). Here, we will follow-up on this work by characterizing colonies with near-normal mutation burden that have been exposed to selected mutagens over a certain period of time in order to determine the landscape of genomic alterations in these cells","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006110","title":"Whole-exome sequencing of Non-muscle Invasive Bladder cancer (NMIBC)","description":null,"abstract":"This WES cohort includes 93 Non-muscle Invasive Bladder cancer (NMIBC) samples and 8 Muscle Invasive Bladder cancer (MIBC) samples.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006111","title":"RNAseq Iron-Treated iPSC-derived Microglia","description":null,"abstract":"Iron accumulation in microglia has been observed in Alzheimer’s disease and other neurodegenerative disorders and is thought to contribute to disease progression through various mechanisms including neuroinflammation. To study the interaction between iron accumulation and inflammation, we treated human induced pluripotent stem cell-derived microglia (iPSC-MG) with an increasing concentration of iron, in combination with inflammatory stimuli such as interferon gamma and amyloid β, and performed RNA sequencing.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006112","title":"RNAseq Iron-Treated iPSC-derived Microglia","description":"Iron accumulation in microglia has been observed in Alzheimer’s disease and other neurodegenerative disorders and is thought to contribute to disease progression through various mechanisms including neuroinflammation. To study the interaction between iron accumulation and inflammation, we treated human induced pluripotent stem cell-derived microglia (iPSC-MG) with an increasing concentration of iron, in combination with inflammatory stimuli such as interferon gamma and amyloid β, and performed RNA sequencing.","abstract":"Iron accumulation in microglia has been observed in Alzheimer’s disease and other neurodegenerative disorders and is thought to contribute to disease progression through various mechanisms including neuroinflammation. To study the interaction between iron accumulation and inflammation, we treated human induced pluripotent stem cell-derived microglia (iPSC-MG) with an increasing concentration of iron, in combination with inflammatory stimuli such as interferon gamma and amyloid β, and performed RNA sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-10T08:36:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006113","title":"Spatio-temporal analysis of prostate tumors in situ suggests pre-existence of treatment-resistant clones","description":"The molecular mechanisms underlying lethal castration-resistant prostate cancer remain poorly understood, with intratumoral heterogeneity a likely contributing factor. To examine the temporal aspects of resistance, we analyzed tumor heterogeneity in needle biopsies collected before and after treatment with androgen deprivation therapy. By doing so, we were able to couple clinical responsiveness and morphological information such as Gleason score to transcriptome-wide data. Our data-driven analysis of transcriptomes identified several distinct intratumoral cell populations, characterized by their unique gene expression profiles. Strikingly, certain cell populations present before treatment exhibited gene expression profiles that matched those of resistant tumor cell clusters, present after treatment. We confirmed that these clusters were resistant by the localization of active androgen receptors to the nuclei in cancer cells post-treatment. Our data also demonstrated that most stromal cells adjacent to resistant clusters do not express the androgen receptor, and we identified differentially expressed genes for these cells. Altogether, this study shows the potential to increase the power in predicting resistant tumors.","abstract":"The molecular mechanisms underlying lethal castration-resistant prostate cancer remain poorly understood, with intratumoral heterogeneity a likely contributing factor. To examine the temporal aspects of resistance, we analyzed tumor heterogeneity in needle biopsies collected before and after treatment with androgen deprivation therapy. By doing so, we were able to couple clinical responsiveness and morphological information such as Gleason score to transcriptome-wide data. Our data-driven analysis of transcriptomes identified several distinct intratumoral cell populations, characterized by their unique gene expression profiles. Strikingly, certain cell populations present before treatment exhibited gene expression profiles that matched those of resistant tumor cell clusters, present after treatment. We confirmed that these clusters were resistant by the localization of active androgen receptors to the nuclei in cancer cells post-treatment. Our data also demonstrated that most stromal cells adjacent to resistant clusters do not express the androgen receptor, and we identified differentially expressed genes for these cells. Altogether, this study shows the potential to increase the power in predicting resistant tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-10T11:37:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006114","title":"Whole Genome sequencing of colorectal cancer patients (SG-BULK-5)","description":"The study was approved by the institutional review board of Singhealth (2018-2795). Ten 5-µm tissue sections were cut using standard microtomy techniques. Each collected cell population was then extracted using the allprep kit. Extracted material was then quantified using a Qubit fluorometer.","abstract":"The study was approved by the institutional review board of Singhealth (2018-2795). Ten 5-µm tissue sections were cut using standard microtomy techniques. Each collected cell population was then extracted using the allprep kit. Extracted material was then quantified using a Qubit fluorometer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-11T03:59:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006115","title":"Differentially methylated CpGs in response to growth hormone administration in children with idiopathic short stature","description":"Background: Recombinant human growth hormone (rhGH) has shown a great growth-promoting potential in children with idiopathic short stature (ISS). However, the response to rhGH differs across individuals, largely due to genetic and epigenetic heterogeneity. Since epigenetic marks on the methylome can be dynamically influenced by GH, we performed a comprehensive pharmaco-epigenomics analysis of DNA methylation changes associated with long-term rhGH administration in children with ISS.\n\nResults: We measured DNA methylation profiles before and after GH treatment (with a duration of ~18 months in average) on 47 healthy children using customized methylC-seq capture sequencing. Their changes were compared and associated with changes in plasma IGF1 by adjusting sex, age, treatment duration, and estimated blood proportions. We observed a considerable inter-individual heterogeneity of DNA methylation changes responding to GH treatment. We identified 267 response-associated differentially methylated cytosines (DMC) that were enriched in promoter regions, CpG islands and blood cell-type specific regulatory elements. Furthermore, the genes associated with these DMCs were enriched in the biology process of \"cell development\", \"neuron differentiation\" and \"developmental growth\", and in the TGF-beta signaling pathway, PPAR Alpha pathway, endoderm differentiation pathway, adipocytokine signaling pathway as well as PI3K-Akt signaling pathway, and cAMP signaling pathway.\n\nConclusion: Our study provides a first insight in DNA methylation changes associated with rhGH administration, which may help understand mechanisms of epigenetic regulation on GH-responsive genes.","abstract":"Background: Recombinant human growth hormone (rhGH) has shown a great growth-promoting potential in children with idiopathic short stature (ISS). However, the response to rhGH differs across individuals, largely due to genetic and epigenetic heterogeneity. Since epigenetic marks on the methylome can be dynamically influenced by GH, we performed a comprehensive pharmaco-epigenomics analysis of DNA methylation changes associated with long-term rhGH administration in children with ISS.\n\nResults: We measured DNA methylation profiles before and after GH treatment (with a duration of ~18 months in average) on 47 healthy children using customized methylC-seq capture sequencing. Their changes were compared and associated with changes in plasma IGF1 by adjusting sex, age, treatment duration, and estimated blood proportions. We observed a considerable inter-individual heterogeneity of DNA methylation changes responding to GH treatment. We identified 267 response-associated differentially methylated cytosines (DMC) that were enriched in promoter regions, CpG islands and blood cell-type specific regulatory elements. Furthermore, the genes associated with these DMCs were enriched in the biology process of \"cell development\", \"neuron differentiation\" and \"developmental growth\", and in the TGF-beta signaling pathway, PPAR Alpha pathway, endoderm differentiation pathway, adipocytokine signaling pathway as well as PI3K-Akt signaling pathway, and cAMP signaling pathway.\n\nConclusion: Our study provides a first insight in DNA methylation changes associated with rhGH administration, which may help understand mechanisms of epigenetic regulation on GH-responsive genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-11T08:34:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006116","title":"Genomic History of the Solomon Islands","description":"The aim of this study was to provide for a better understanding of the genetic relationships among and between populations of Near and Remote Oceania, with a focus on the initial settlement of the Solomon Islands and their role in the first dispersal of people from Near into Remote Oceania.\nIrina Pugach, Ana T Duggan, D Andrew Merriwether, Françoise R Friedlaender, Jonathan S Friedlaender, Mark Stoneking, \"The Gateway from Near into Remote Oceania: New Insights from Genome-Wide Data\", Molecular Biology and Evolution, Volume 35, Issue 4, April 2018, Pages 871–886","abstract":"The aim of this study was to provide for a better understanding of the genetic relationships among and between populations of Near and Remote Oceania, with a focus on the initial settlement of the Solomon Islands and their role in the first dispersal of people from Near into Remote Oceania.\nIrina Pugach, Ana T Duggan, D Andrew Merriwether, Françoise R Friedlaender, Jonathan S Friedlaender, Mark Stoneking, \"The Gateway from Near into Remote Oceania: New Insights from Genome-Wide Data\", Molecular Biology and Evolution, Volume 35, Issue 4, April 2018, Pages 871–886","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-11T11:13:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006117","title":"CDK4 phosphorylation predicts high sensitivity of malignant pleural mesotheliomas to CDK4/6 inhibition","description":null,"abstract":"Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited therapeutic options. In this study, we evaluated the impact of CDK4/6 inhibition by palbociclib in a large panel of MPM cell lines, including 19 patient-derived primary cell lines, using a variety of approaches including RNA sequencing. Palbociclib used alone sufficed to strongly and durably inhibit the proliferation of 23 out of 28 MPM cell lines, indicating a unique sensitivity of MPM to CDK4/6 inhibition. Importantly, insensitivity to palbociclib was mostly explained by the lack of active T172-phosphorylated CDK4. This was associated with the high p16INK4A (CDKN2A) levels that accompany RB1 defects or inactivation, and also (unexpectedly) cyclin E1 overexpression in the presence of wild-type RB1. Prolonged treatment with palbociclib irreversibly inhibited proliferation despite re-induction of cell cycle genes upon drug washout. A senescence-associated secretory phenotype (SASP) including various potentially immunogenic components was also irreversibly induced. Phosphorylated CDK4 was detected in 80% of MPM tumors indicating their intrinsic sensitivity to CDK4/6 inhibitors. The absence of this phosphorylation in some highly proliferative MPM tumors was linked to partial deletions of RB1, leading to very high p16 (CDKN2A) expression. Our study strongly supports the clinical evaluation of CDK4/6 inhibitory drugs for MPM treatment, in monotherapy or combination therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-11T16:39:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006118","title":"Conserved features of TERT promoter duplications reveal an activation mechanism that mimics hotspot mutations in cancer","description":"Mutations in the TERT promoter are the single most common non-coding mutation in cancer and represent the genetic underpinnings of tumor cell immortality. Beyond the two most common point mutations, G228A and G250A, which selectively recruit the ETS factor GABP to activate TERT, the significance of other variants in the TERT promoter are unknown. We identified duplications of wildtype sequence within the core promoter region of TERT in 7 different cancer types that have strikingly similar features including size, insertion position, and inclusion of one of the native ETS motifs. Each duplication activates the TERT promoter to a similar level as G228A and G250A and is critically dependent on the insertion site. The GABP tetramer binds to the TERT duplicated promoter sequence by virtue of the native ETS motif and its duplicated version with precise spacing, and it is necessary for the transcriptional activation by all duplications tested. Spatiotemporal analysis in a multifocal glioblastoma shows the duplication is clonal and its activation of TERT is readily detectable at the single cell level and in bulk tumor tissue. We conclude that recurrent TERT promoter duplications of the native ETS sequence are functionally and mechanistically equivalent to the hotspot mutations that confer tumor cell immortality. The shared mechanism of these divergent somatic genetic alterations suggests a strong selective pressure for recruitment of the GABP tetramer to activate TERT.","abstract":"Mutations in the TERT promoter are the single most common non-coding mutation in cancer and represent the genetic underpinnings of tumor cell immortality. Beyond the two most common point mutations, G228A and G250A, which selectively recruit the ETS factor GABP to activate TERT, the significance of other variants in the TERT promoter are unknown. We identified duplications of wildtype sequence within the core promoter region of TERT in 7 different cancer types that have strikingly similar features including size, insertion position, and inclusion of one of the native ETS motifs. Each duplication activates the TERT promoter to a similar level as G228A and G250A and is critically dependent on the insertion site. The GABP tetramer binds to the TERT duplicated promoter sequence by virtue of the native ETS motif and its duplicated version with precise spacing, and it is necessary for the transcriptional activation by all duplications tested. Spatiotemporal analysis in a multifocal glioblastoma shows the duplication is clonal and its activation of TERT is readily detectable at the single cell level and in bulk tumor tissue. We conclude that recurrent TERT promoter duplications of the native ETS sequence are functionally and mechanistically equivalent to the hotspot mutations that confer tumor cell immortality. The shared mechanism of these divergent somatic genetic alterations suggests a strong selective pressure for recruitment of the GABP tetramer to activate TERT.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-12T00:10:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006119","title":"Total RNA sequencing of RNA from testicular tissue","description":null,"abstract":"We aimed to determine whether gene expression and splicing is altered in M1911 with infertility due to round spermatid arrest. To this end we performed total RNA sequencing of RNA from testicular tissue of this man.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-12T12:00:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006120","title":"Stromal-induced epithelial-mesenchymal transition induces drug resistance in acute lymphoblastic leukemia","description":"Bone marrow (BM) microenvironment-induced drug resistance in acute lymphoblastic leukemia (ALL) is thought to be mediated by intercellular interaction of leukemic cells with BM niches, but the mechanistic basis of resistance is poorly understood. Here, we genomic and functional analyses, we show that ALL-BM mesenchymal stromal cells (MSC) interactions encompass direct cell-cell adhesion via integrin α4β1, uni-directional secretion of soluble factors from MSC to ALL, and bidirectional transfer of cellular vesicles through tunneling nanotubes. We show that this crosstalk drives an epithelial-mesenchymal transition (EMT)-like program in ALL cells adhering to MSC, thereby triggering stem cell-like features including drug resistance and survival advantage. Moreover, single-cell RNA sequencing of cell line and primary ALL samples identified a hybrid cell state derived from B-ALL adhered to MSC, that exhibits both B-ALL and MSC gene signatures that are orchestrated by an EMT-like program. Multiple EMT-activating pathways including WNT/β-catenin, cytokine/STAT3, TGFβ, NOTCH1, and NF-κB-dependent signaling pathways are activated in MSC-adherent ALL cells; however, only the inhibition of either WNT/β-catenin or cytokine/STAT3 pathway could attenuate the survival and drug resistance of ALL cells adherent to MSC. Notably, we identified that this hybrid cell state exhibited elevated WNT/β-catenin-mediated transcriptional activity. Finally, we show that blocking of the interaction of β-catenin and CBP interaction abrogates the survival and drug resistance of ALL cells adhered to MSC, indicating that targeting of an EMT-like program is potential therapeutic regimen in targeting cell extrinsically acquired drug resistance in ALL.","abstract":"Bone marrow (BM) microenvironment-induced drug resistance in acute lymphoblastic leukemia (ALL) is thought to be mediated by intercellular interaction of leukemic cells with BM niches, but the mechanistic basis of resistance is poorly understood. Here, we genomic and functional analyses, we show that ALL-BM mesenchymal stromal cells (MSC) interactions encompass direct cell-cell adhesion via integrin α4β1, uni-directional secretion of soluble factors from MSC to ALL, and bidirectional transfer of cellular vesicles through tunneling nanotubes. We show that this crosstalk drives an epithelial-mesenchymal transition (EMT)-like program in ALL cells adhering to MSC, thereby triggering stem cell-like features including drug resistance and survival advantage. Moreover, single-cell RNA sequencing of cell line and primary ALL samples identified a hybrid cell state derived from B-ALL adhered to MSC, that exhibits both B-ALL and MSC gene signatures that are orchestrated by an EMT-like program. Multiple EMT-activating pathways including WNT/β-catenin, cytokine/STAT3, TGFβ, NOTCH1, and NF-κB-dependent signaling pathways are activated in MSC-adherent ALL cells; however, only the inhibition of either WNT/β-catenin or cytokine/STAT3 pathway could attenuate the survival and drug resistance of ALL cells adherent to MSC. Notably, we identified that this hybrid cell state exhibited elevated WNT/β-catenin-mediated transcriptional activity. Finally, we show that blocking of the interaction of β-catenin and CBP interaction abrogates the survival and drug resistance of ALL cells adhered to MSC, indicating that targeting of an EMT-like program is potential therapeutic regimen in targeting cell extrinsically acquired drug resistance in ALL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-14T02:08:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006121","title":"Peripheral blood DNA methylation profiles of Crohn's disease patients with endoscopic post-operative recurrence","description":null,"abstract":"In this study, we investigated the DNA methylome from peripheral blood to investigate the differences between patients with and without endoscopic post operative recurrence.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006122","title":"The evolutionary dynamics of human colorectal cancer using single-gland spatial multi-omic profiling of DNA, RNA and chromatin.","description":null,"abstract":"Deciphering the mechanisms of colorectal cancer growth, progression and dissemination in each individual patient,","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-14T19:35:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006123","title":"Genetic immune escape landscape in primary and metastatic cancer","description":"Immune surveillance escape is a hallmark of tumorigenesis1. Multiple studies have characterized the immune escape landscape across several untreated early-stage primary cancer types2–4. However, whether late-stage treated metastatic tumors present differences in genetic immune escape (GIE) prevalence and dynamics remains unclear. Here, we performed a pan-cancer characterization of GIE prevalence across six immune escape pathways in 6,457 uniformly processed Whole Genome Sequencing (WGS) tumor samples including 58 cancer types from 1,943 primary untreated patients and 4,514 metastatic patients. To effectively address the complexity of the Human Leukocyte Antigen (HLA-I) locus and to characterize its tumor status, we developed LILAC, an open-source integrative framework. We demonstrate that one in four tumors harbor GIE alterations, with high mechanistic and frequency variability across cancer types. GIE prevalence is highly consistent between primary and metastatic tumors for most cancer types with few exceptions such as prostate and thyroid carcinomas that have increased immune evasion frequencies in metastatic tumors. Positive selection analysis revealed that GIE alterations are frequently selected for in tumor evolution and that focal LOH of HLA-I, unlike non-focal LOH of HLA-I, tends to lose the HLA allele that presents the largest neoepitope repertoire. We also unraveled tumor genomic features contributing to immune escape incidence, including DNA repair deficiency, APOBEC activity, tobacco associated mutation load and viral DNA integration. Finally, there is a strong tendency for mid and high tumor mutation burden (TMB) tumors to preferentially select LOH of HLA-I for GIE whereas hypermutated samples favor global immune evasion strategies. Our results indicate that genetic immune escape is generally a pre-metastatic event during tumor evolution and that tumors adapt different strategies depending on their neoepitope burden.","abstract":"Immune surveillance escape is a hallmark of tumorigenesis1. Multiple studies have characterized the immune escape landscape across several untreated early-stage primary cancer types2–4. However, whether late-stage treated metastatic tumors present differences in genetic immune escape (GIE) prevalence and dynamics remains unclear. Here, we performed a pan-cancer characterization of GIE prevalence across six immune escape pathways in 6,457 uniformly processed Whole Genome Sequencing (WGS) tumor samples including 58 cancer types from 1,943 primary untreated patients and 4,514 metastatic patients. To effectively address the complexity of the Human Leukocyte Antigen (HLA-I) locus and to characterize its tumor status, we developed LILAC, an open-source integrative framework. We demonstrate that one in four tumors harbor GIE alterations, with high mechanistic and frequency variability across cancer types. GIE prevalence is highly consistent between primary and metastatic tumors for most cancer types with few exceptions such as prostate and thyroid carcinomas that have increased immune evasion frequencies in metastatic tumors. Positive selection analysis revealed that GIE alterations are frequently selected for in tumor evolution and that focal LOH of HLA-I, unlike non-focal LOH of HLA-I, tends to lose the HLA allele that presents the largest neoepitope repertoire. We also unraveled tumor genomic features contributing to immune escape incidence, including DNA repair deficiency, APOBEC activity, tobacco associated mutation load and viral DNA integration. Finally, there is a strong tendency for mid and high tumor mutation burden (TMB) tumors to preferentially select LOH of HLA-I for GIE whereas hypermutated samples favor global immune evasion strategies. Our results indicate that genetic immune escape is generally a pre-metastatic event during tumor evolution and that tumors adapt different strategies depending on their neoepitope burden.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-15T14:34:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006124","title":"Spatial atlas of clonal copy number alterations in co-existing benign and malignant tissue","description":"Defining the transition from benign to malignant tissue is fundamental to improve early diagnosis of cancer. Here, we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We employed spatially resolved transcriptomics to infer spatial copy number variations in &gt;120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.","abstract":"Defining the transition from benign to malignant tissue is fundamental to improve early diagnosis of cancer. Here, we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We employed spatially resolved transcriptomics to infer spatial copy number variations in &gt;120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-15T15:06:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006125","title":"Engineered Human Primary T Cell transcriptome study","description":"Study of transcriptome responses to different human T cell engineering approaches.","abstract":"Study of transcriptome responses to different human T cell engineering approaches.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-15T17:50:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006126","title":"early-stage ESCC sequencing study","description":"We performed a comprehensive multi-omics analysis of 786 trace-tumor-samples from 154 esophageal squamous cell carcinoma phase (ESCC) patients, covering 9 histopathological stages in 3 phases as nontumor phase (NT phase), intraepithelial neoplasia phase (IEN phase), and ESCC phase. Proteogenomics elucidated the stage-specific molecular characterization and defined the cancer-driving waves along with the mutation accumulation in EC progression. The integrated multi-omics uncovered the chromosome 3q gain was the key event in the transmit from the NT to IEN phase, disclosed the top mutation of TP53 enhanced cell cycle and DNA replication in the IEN phase, and revealed the ESCC phase mutations of AKAP9 and MCAF1 elevated glycolysis and Wnt signaling, respectively. Furthermore, the trajectory analysis identified 6 major tracks related to different clinical features during ESCC progression. Growingly enhanced and hyperphosphorylated phosphoglycerate kinase 1 (PGK1, S203) was detected and considered as a drug target in ESCC progression. Collectively, this study provides insight into the understanding of ESCC molecular mechanism and a valuable resource for the development of therapeutic targets.","abstract":"We performed a comprehensive multi-omics analysis of 786 trace-tumor-samples from 154 esophageal squamous cell carcinoma phase (ESCC) patients, covering 9 histopathological stages in 3 phases as nontumor phase (NT phase), intraepithelial neoplasia phase (IEN phase), and ESCC phase. Proteogenomics elucidated the stage-specific molecular characterization and defined the cancer-driving waves along with the mutation accumulation in EC progression. The integrated multi-omics uncovered the chromosome 3q gain was the key event in the transmit from the NT to IEN phase, disclosed the top mutation of TP53 enhanced cell cycle and DNA replication in the IEN phase, and revealed the ESCC phase mutations of AKAP9 and MCAF1 elevated glycolysis and Wnt signaling, respectively. Furthermore, the trajectory analysis identified 6 major tracks related to different clinical features during ESCC progression. Growingly enhanced and hyperphosphorylated phosphoglycerate kinase 1 (PGK1, S203) was detected and considered as a drug target in ESCC progression. Collectively, this study provides insight into the understanding of ESCC molecular mechanism and a valuable resource for the development of therapeutic targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-16T06:30:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006127","title":"RNASeq of Calcoco2 in beta and fat cell lines","description":"Investigation of the function of Calcoco2 by knocking it down in beta and fat cell lines.","abstract":"Investigation of the function of Calcoco2 by knocking it down in beta and fat cell lines.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-16T06:49:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006128","title":"HCA_Immune_UAI_Paediatric_WSSS_RNA_Managed_Access","description":"Comparison of immune populations in adenoid tissue in patients with and without history of otitis media","abstract":"Comparison of immune populations in adenoid tissue in patients with and without history of otitis media","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006129","title":"HCA_Immune_UAI_Paediatric_WSSS_Spatial_Managed_Access","description":"Comparison of immune populations in adenoid tissue in patients with and without history of otitis media","abstract":"Comparison of immune populations in adenoid tissue in patients with and without history of otitis media","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006130","title":"Vietnam_Rotavirus_Vaccine_Perturbation_Study","description":"This study assesses the contribution of host genetics to live-attenuated rotavirus vaccine (Rotarix) response, in a cohort of approx. 800 infants in HCMC, Vietnam. Patients are whole-genome sequenced, and longitudinal measurements of the blood transcriptome are taken before and after vaccine doses. This genetic and transcriptomic data is integrated with serological, clinical, and vaccine failure phenotypes. The study aims to characterise genetic variation (quantitative trait loci) that influences longitudinal transcriptomic response and other vaccine phenotypes such as vaccine induced antibody titres and vaccine failure events, whilst forming hypotheses regarding the immune mechanisms by which these variants have their effects. Genetic variation in the HLA region is of particular interest, as it is known to be associated with responses to multiple licensed vaccines. Whole genome sequencing data from patient blood samples will allow us to infer genome-wide SNP variation, structural variation, and variation in HLA alleles. The study is run in collaboration with the Oxford University Clinical Research Unit (OUCRU) in Ho Chi Minh City, Vietnam. Recruitment, sampling, clinical work, serological work, active surveillance for vaccine failure, and microbiological work will be based at OUCRU. RNA-seq, whole genome sequencing, and computational analysis will be performed at the Wellcome Sanger Institute.\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"This study assesses the contribution of host genetics to live-attenuated rotavirus vaccine (Rotarix) response, in a cohort of approx. 800 infants in HCMC, Vietnam. Patients are whole-genome sequenced, and longitudinal measurements of the blood transcriptome are taken before and after vaccine doses. This genetic and transcriptomic data is integrated with serological, clinical, and vaccine failure phenotypes. The study aims to characterise genetic variation (quantitative trait loci) that influences longitudinal transcriptomic response and other vaccine phenotypes such as vaccine induced antibody titres and vaccine failure events, whilst forming hypotheses regarding the immune mechanisms by which these variants have their effects. Genetic variation in the HLA region is of particular interest, as it is known to be associated with responses to multiple licensed vaccines. Whole genome sequencing data from patient blood samples allows us to infer genome-wide SNP variation, structural variation, and variation in HLA alleles; and test their association with vaccine outcome phenotypes.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006131","title":"Cell Rep","description":null,"abstract":"Testing only","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006132","title":"Denisova admixture in Southeast Asia and Oceania","description":"Genome-wide data from populations from south Asia, Southeast Asia, and Oceania were analyzed for signatures of Denisova admixture to infer the history of human migration to this part of the world","abstract":"Genome-wide data from populations from south Asia, Southeast Asia, and Oceania were analyzed for signatures of Denisova admixture to infer the history of human migration to this part of the world","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-17T13:15:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006133","title":"Discriminating Th17.1 cell driven sarcoidosis-like inflammation from relapse after anti-BCMA CAR T cells in multiple myeloma","description":"We present a case study on sarcoidosis-like flare-up after Idecabtagen Vicleucel (Ide-cel), a BCMA targeting CAR T cell therapy, and identified a Th17.1 driven autoimmune mechanism as the biological underpinning of this phenomenon using single-cell RNA-seq analysis. Furthermore, single-cell RNA-seq allowed to discriminate between immune-mediated changes and true relapse after CAR T cell treatment.","abstract":"We present a case study on sarcoidosis-like flare-up after Idecabtagen Vicleucel (Ide-cel), a BCMA targeting CAR T cell therapy, and identified a Th17.1 driven autoimmune mechanism as the biological underpinning of this phenomenon using single-cell RNA-seq analysis. Furthermore, single-cell RNA-seq allowed to discriminate between immune-mediated changes and true relapse after CAR T cell treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-18T11:05:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006134","title":"Longitudinal monitoring of disease burden and response using ctDNA from dried blood spots in xenograft models","description":null,"abstract":"Whole genome sequencing (WGS) of circulating tumour DNA (ctDNA) is now a clinically important biomarker for predicting therapy response, disease burden and disease progression. However, the translation of ctDNA monitoring into vital pre-clinical PDX models has not been possible owing to low circulating blood volumes in small rodents. Here, we describe the longitudinal detection and monitoring of ctDNA from minute volumes of blood in PDX mice. We developed a xenograft Tumour Fraction (xTF) metric using shallow WGS of dried blood spots (DBS), and demonstrate its application to quantify disease burden, monitor treatment response and predict disease outcome in a pre-clinical study of PDX mice. Further, we show how our DBS-based ctDNA assay can be used to detect gene-specific copy number changes and examine the copy number landscape over time. Use of sequential DBS ctDNA assays could transform future trial designs in both mice and patients.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-18T12:52:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006135","title":"Stage-specific gene and transcript dynamics in human male germ cells","description":"The testis is one of the most transcriptionallyactive organs, however how germ cell differentiation is controlled at the molecular level remains largely unknown. To study global transcriptional dynamics during human spermatogenesis we sequenced total RNA of human testicular biopsies with 5 specific histological phenotypes: Sertoli cell-only (SCO, n=3), spermatogenic arrests at the spermatogonial (SPG, n=4), spermatocyte (SPC, n=3), and spermatid (SPD, n=3) level, as well as normal spermatogenesis (Normal, n=3). To our knowledge, this work provides the most complete capture of the transcriptome and its dynamics during human spermatogenesis to date.","abstract":"The testis is one of the most transcriptionallyactive organs, however how germ cell differentiation is controlled at the molecular level remains largely unknown. To study global transcriptional dynamics during human spermatogenesis we sequenced total RNA of human testicular biopsies with 5 specific histological phenotypes: Sertoli cell-only (SCO, n=3), spermatogenic arrests at the spermatogonial (SPG, n=4), spermatocyte (SPC, n=3), and spermatid (SPD, n=3) level, as well as normal spermatogenesis (Normal, n=3). To our knowledge, this work provides the most complete capture of the transcriptome and its dynamics during human spermatogenesis to date.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-18T18:07:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006136","title":"single cell RNA-seq and ATAC-seq of human fetal forebrain tissue","description":"Oligodendrogenesis in the human central nervous system has been mainly observed at the second trimester of gestation, a much later developmental stage compared to mouse. Here we characterize the transcriptomic neural diversity in the human forebrain at post conceptual weeks (PCW) 8 to 10, using single-cell RNA-Seq. We find evidence of the emergence of a first wave of oligodendrocyte lineage cells as early as PCW 8, which we also confirm at the epigenomic level with single-cell ATAC-Seq. Using regulatory network inference, we predict key transcriptional events leading to the specification of oligodendrocyte precursor cells (OPCs).  Moreover, by profiling the spatial expression of fifty key genes using In Situ Sequencing (ISS), we identify regions in the human ventral fetal forebrain where oligodendrogenesis first occurs. Our results indicate evolutionary conservation of the first wave of oligodendrogenesis between mouse and human and describe regulatory mechanisms involved in human OPC specification.","abstract":"Oligodendrogenesis in the human central nervous system has been mainly observed at the second trimester of gestation, a much later developmental stage compared to mouse. Here we characterize the transcriptomic neural diversity in the human forebrain at post conceptual weeks (PCW) 8 to 10, using single-cell RNA-Seq. We find evidence of the emergence of a first wave of oligodendrocyte lineage cells as early as PCW 8, which we also confirm at the epigenomic level with single-cell ATAC-Seq. Using regulatory network inference, we predict key transcriptional events leading to the specification of oligodendrocyte precursor cells (OPCs).  Moreover, by profiling the spatial expression of fifty key genes using In Situ Sequencing (ISS), we identify regions in the human ventral fetal forebrain where oligodendrogenesis first occurs. Our results indicate evolutionary conservation of the first wave of oligodendrogenesis between mouse and human and describe regulatory mechanisms involved in human OPC specification.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-19T08:41:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006137","title":"Smoking-dependent expression alterations in nasal epithelium reveal immune impairment linked to germline variation and lung cancer risk","description":null,"abstract":"To examine whether clinical risk stratification can be improved upon by\nthe addition of genetic data, and to explore the mechanisms of the persisting\nrisk in former smokers, we have analyzed transcriptomic data from accessible\nairway tissues of 487 subjects. We developed a model to assess smoking\nassociated gene expression changes and their reversibility after smoking is\nstopped, in both healthy subjects and clinic patients. We find persistent smokingassociated immune alterations to be a hallmark of the clinic patients. Integrating\nprevious GWAS data using a transcriptional network approach, we demonstrate\nthat the same immune and interferon related pathways are strongly enriched for\ngenes linked to known genetic risk factors, demonstrating a causal relationship\nbetween immune alteration and lung cancer risk. Finally, we used accessible\nairway transcriptomic data to derive a non-invasive lung cancer risk classifier.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-03-22T17:12:33.650723+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006138","title":"Drug screen in iPSC-Neurons identifies nucleoside analogs as inhibitors of (G4C2)n expression in C9orf72 ALS/FTD","description":"To investigate the mode of action and potential side-effects we analyzed differential gene expression in\npost-mitotic C9orf72 iPSC-Neurons by RNAseq","abstract":"To investigate the mode of action and potential side-effects we analyzed differential gene expression in\npost-mitotic C9orf72 iPSC-Neurons by RNAseq","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-21T00:58:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006139","title":"The transcriptomic response of skeletal muscle in life-long high-level trained and untrained men and women after acute exercise","description":"To investigate the influence of lifelong exercise training on the response of skeletal muscle to a bout of acute exercise we generated global transcriptomic data from long-term endurance (8 men, 8 women) and strength (8 men, 8 women) trained individuals and healthy age-matched untrained controls (8 men, 8 women). Skeletal muscle biopsies were taken from M. vastus lateralis before, directly after, and after 1h and 3hrs following acute exercise. All subjects completed one bout of acute endurance exercise and one bout of acute resistance exercise, separated by 4-8 weeks. All 384 samples were multiplexed in 4 lanes and sequenced (2x250bp paired end) on the Illumina NovaSeq 6000.","abstract":"To investigate the influence of lifelong exercise training on the response of skeletal muscle to a bout of acute exercise we generated global transcriptomic data from long-term endurance (8 men, 8 women) and strength (8 men, 8 women) trained individuals and healthy age-matched untrained controls (8 men, 8 women). Skeletal muscle biopsies were taken from M. vastus lateralis before, directly after, and after 1h and 3hrs following acute exercise. All subjects completed one bout of acute endurance exercise and one bout of acute resistance exercise, separated by 4-8 weeks. All 384 samples were multiplexed in 4 lanes and sequenced (2x250bp paired end) on the Illumina NovaSeq 6000.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-21T11:08:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006140","title":"Loss of Epigenetic Barrier is Required for Enhancer Hijacking-Mediated Oncogenic Transcription","description":"Structural variants (SVs) involving enhancer hijacking can disrupt chromatin topologies to cause oncogene activation in cancer genomes, yet the molecular determinants for the transcriptional output of enhancer hijacking remain largely unknown. We developed a multimodal approach to integrate genome sequencing, chromosome conformation, and sequence-based deep learning for quantitative analysis of transcriptional effects and structural reorganization imposed by SVs in leukemic genomes. We identified candidate pathogenic SVs including recurrent t(5;14) translocations that cause the hijacking of BCL11B enhancers for oncogenic activation of TLX3-dependent transcriptional programs. By engineering patient-associated t(5;14) in isogenic leukemia cells, we uncovered an uncharacterized mechanism whereby DNA methylation serves as an epigenetic barrier to enhancer hijacking and loss of epigenetic barrier is a molecular determinant for the transcriptional output of pathogenic SVs. Hence, leveraging the epigenetic barriers of SV-mediated oncogenic programs may provide new opportunities to reprogram gene regulation as epigenetic therapies in human disease.","abstract":"Structural variants (SVs) involving enhancer hijacking can disrupt chromatin topologies to cause oncogene activation in cancer genomes, yet the molecular determinants for the transcriptional output of enhancer hijacking remain largely unknown. We developed a multimodal approach to integrate genome sequencing, chromosome conformation, and sequence-based deep learning for quantitative analysis of transcriptional effects and structural reorganization imposed by SVs in leukemic genomes. We identified candidate pathogenic SVs including recurrent t(5;14) translocations that cause the hijacking of BCL11B enhancers for oncogenic activation of TLX3-dependent transcriptional programs. By engineering patient-associated t(5;14) in isogenic leukemia cells, we uncovered an uncharacterized mechanism whereby DNA methylation serves as an epigenetic barrier to enhancer hijacking and loss of epigenetic barrier is a molecular determinant for the transcriptional output of pathogenic SVs. Hence, leveraging the epigenetic barriers of SV-mediated oncogenic programs may provide new opportunities to reprogram gene regulation as epigenetic therapies in human disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-21T14:39:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006141","title":"Integrated single-cell profiling dissects cell-state-specific enhancer landscapes of human tumor infiltrating T cells.","description":null,"abstract":"Despite extensive studies on the chromatin landscape of exhausted T cells, the transcriptional wiring underlying functional and dysfunctional states of human tumor infiltrating lymphocytes (TILs) is incompletely understood. Here, we identify tissue-specific and general gene-regulatory landscapes in the wide breadth of CD8+ TIL functional states covering four cancer entities using single-cell chromatin profiling. We map enhancer-promoter interactions in human TILs by integrating single-cell chromatin accessibility with single-cell RNA-seq data from tumor entity-matching samples and prioritize key elements by super enhancer analysis. Our analysis reveals a human core chromatin trajectory to TIL dysfunction and identifies key enhancers, transcriptional regulators, and deregulated target genes involved in this process. Finally, we validate enhancer regulation at loci encoding PD1, TCF1, and TIM3 by targeting non-coding regulatory elements with potent CRISPR activators and repressors. In summary, our study advances the understanding of molecular regulation of TIL (dys-)function and provides a framework for modulating immunotherapeutic relevant TIL genes via their enhancers.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-21T16:03:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006142","title":"Genome-wide cell-free DNA termini in patients with cancer","description":"The structure, fragmentation patterns and terminal sequences of cell-free DNA (cfDNA) are altered by nucleases and biological mechanisms in the blood of cancer patients. \nThe cfDNA fragment-end composition recovered from low coverage WGS (&lt;1 fold coverage) using a bespoke software (FrEIA) is aberrant in the plasma from cancer patient (n = 418, 655 samples) compared to controls (n = 117). As a standalone test FrEIA allows detection down to ~0.2% tumor fraction in vitro and in silico at 95% specificity, leading to a sensitivity of ~71% for detecting lung cancer (14/22 stage I-II, 27/38 stage III, 92/127 stage IV) and ~68% for detecting esophageal adenocarcinoma (26/44 stage II, 46/62 stage III). \nAdditional cfDNA biological patterns can be  combined with FrEIA increasing the diagnostic potential of low coverage WGS at minimal cost (mean AUROC = 0.96). Integrating multiple cfDNA biological signal augments the diagnostic performance of liquid biopsy.","abstract":"The structure, fragmentation patterns and terminal sequences of cell-free DNA (cfDNA) are altered by nucleases and biological mechanisms in the blood of cancer patients. \nThe cfDNA fragment-end composition recovered from low coverage WGS (&lt;1 fold coverage) using a bespoke software (FrEIA) is aberrant in the plasma from cancer patient (n = 418, 655 samples) compared to controls (n = 117). As a standalone test FrEIA allows detection down to ~0.2% tumor fraction in vitro and in silico at 95% specificity, leading to a sensitivity of ~71% for detecting lung cancer (14/22 stage I-II, 27/38 stage III, 92/127 stage IV) and ~68% for detecting esophageal adenocarcinoma (26/44 stage II, 46/62 stage III). \nAdditional cfDNA biological patterns can be  combined with FrEIA increasing the diagnostic potential of low coverage WGS at minimal cost (mean AUROC = 0.96). Integrating multiple cfDNA biological signal augments the diagnostic performance of liquid biopsy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-22T07:42:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006143","title":"FACS sorting of ploidy populations in an undifferentiated soft tissue sarcoma for RRBS","description":"Groups of cells belonging to different ploidy populations (based on PI staining) were collected from an undifferentiated soft tissue sarcoma. The different ploidy populations underwent RRBS, after which copy number signatures for the ploidy-sorted populations and the bulk population were extracted.","abstract":"Groups of cells belonging to different ploidy populations (based on PI staining) were collected from an undifferentiated soft tissue sarcoma. The different ploidy populations underwent RRBS, after which copy number signatures for the ploidy-sorted populations and the bulk population were extracted.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-22T09:29:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006144","title":"USARC 10X Genomics Single Cell DNA Sequencing Data","description":"We investigated the impact of ploidy heterogeneity on copy number inference at a single cell level using fluorescence-activated cell sorted (FACS) nuclei from an undifferentiated soft tissue sarcoma. FACS revealed the presence of three aberrant subpopulations, including a haploid, a near diploid and a whole genome doubled population. Once sorted, single cell nuclei underwent whole genome sequencing using the chromium CNV single cell DNA library kit (10X Genomics). We sequenced single normal nuclei (2n) and single aberrant / tumour nuclei (1n, 2n and 2n+).","abstract":"We investigated the impact of ploidy heterogeneity on copy number inference at a single cell level using fluorescence-activated cell sorted (FACS) nuclei from an undifferentiated soft tissue sarcoma. FACS revealed the presence of three aberrant subpopulations, including a haploid, a near diploid and a whole genome doubled population. Once sorted, single cell nuclei underwent whole genome sequencing using the chromium CNV single cell DNA library kit (10X Genomics). We sequenced single normal nuclei (2n) and single aberrant / tumour nuclei (1n, 2n and 2n+).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-22T09:46:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006145","title":"Tracing the timing of twinning using somatic mutations","description":"We use whole-genome sequencing of monozygotic twins to detect somatic mutations to infer the cellular history of the twinning event. We recruited monozygotic twins with varying degrees of fetal membranes to compare the twinning events between theses subsets.","abstract":"We use whole-genome sequencing of monozygotic twins to detect somatic mutations to infer the cellular history of the twinning event. We recruited monozygotic twins with varying degrees of fetal membranes to compare the twinning events between theses subsets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006146","title":"UPD detection from trio WGS","description":"We implemented a pipeline to detect uniparental disomy from the whole-genome sequence data of parent-child trio. It can detect both uniparental isodisomy and uniparental heterodisomy, and provides a visual plot for interpretation.","abstract":"We implemented a pipeline to detect uniparental disomy from the whole-genome sequence data of parent-child trio. It can detect both uniparental isodisomy and uniparental heterodisomy, and provides a visual plot for interpretation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006147","title":"Whole exome sequencing study of cholesteatoma patients from affected families","description":"This study used whole exome sequencing on 21 patients with cholesteatoma from 10 families in order to identify variants that may attribute to cholesteatoma aetiology.","abstract":"This study used whole exome sequencing on 21 patients with cholesteatoma from 10 families in order to identify variants that may attribute to cholesteatoma aetiology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-23T09:18:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006148","title":"Genomic profiling of metastatic basal cell carcinoma reveals candidate drivers of disease and therapeutic targets","description":null,"abstract":"We assessed the clinicopathologic characteristics of 17 patients with metastatic BCC and pursued whole-exome sequencing of tumor and germline DNA from 8 patients. Genomic profiling revealed aberrant activation of Hedgehog signaling, alterations in regulators of GLI transcriptional activity, in kinases and members of Notch and Hippo signaling. Matched local recurrences of primary BCCs and metastases from three patients provided evidence of a clonal origin in all cases. Mutations in genes associated with YAP inhibition and negative regulation of WNT signaling were found exclusively in hematogenously-spread lung metastases. Metastatic BCCs were enriched for mutations in YAP/TAZ binding domain of TEAD transcriptional factors, RET, HGF and PI3K/AKT signaling compared with an independent cohort of low clinical risk BCCs. Our results implicate Hippo, WNT and PI3K/AKT dysregulation in metastatic progression of BCCs, making these potential therapeutic targets in metastatic disease.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-24T04:33:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006149","title":"Innovate_UK___MinLib_Screen","description":"The study aims to perform genome-wide loss-of-function CRISPR-Cas9 screens across genetically annotated human organoid lines to identify synthetic-lethal interaction between cancer genomes and targeted gene deletions.  These screens are performed using the Human minimal library system on cancer lines and patient derived organoids.  \n\nAll sequencing is performed on PCR products from the amplification of gRNA segments introduced into the lines.","abstract":"The goal of this project is to identify genetic drivers of cancers and use these results to probe novel drug targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006150","title":"Innovate_UK___Dual_guide_Screen","description":"he study aims to perform genome-wide loss-of-function CRISPR-Cas9 screens across genetically annotated human organoid lines/Cell lines to identify target combinations in KRAS-mutant colorectal lines.  \nAll sequencing is performed on PCR products from the amplification of gRNA segments introduced into the lines.","abstract":"The goal of this project is to identify genetic drivers of cancers and use these results to probe novel drug targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006151","title":"HSC_population_dynamics_in_perturbation___71F1_samples","description":"The aim of this project is to characterise how the systemic environment shapes the clonal landscape in \nadult humans and how perturbations affect this landscape. We are collecting longitudinal samples from \npatients before and after chemotherapy, in order to perform whole genome sequencing on their HSCs \nand, using patterns of shared and unique mutations, construct a phylogenetic tree of each patient’s \nHSCs. This will allow us to interrogate how clonal composition changes in response to chemotherapy, \nshedding insight into the fitness of mutations with respect to age and treatment.\nThe questions I want to answer: \n1. Are mutations that gave some HSCs an advantage, which resulted in their clonal expansion, still \nadvantageous in the new environment? Does chemotherapy favour some mutations over others? \n2. How do chemotherapies of different intensities affect the clonal landscape of HSCs? \n3. How does ageing affect the ability of the hematopoietic system to recover after chemotherapy? Are \nany clinical variables associated with improved recovery? \n4. Does the population of HSCs remain unchanged? \n5. How do different chemotherapies contribute to mutagenesis of HSCs?","abstract":"Background \nWith age, somatic mutations accumulate in normal dividing cells, including hematopoietic stem cells \n(HSCs). It appears that some mutations provide HSCs with a fitness advantage, allowing their mutant \ndaughter blood cells to disproportionately expand (Jaiswal &amp; Ebert, 2019). The phenomenon is termed \nclonal hematopoiesis (CH) and it is associated with ageing as well as hematologic malignancies, \ncardiovascular disease and all-cause mortality (Genovese et al., 2014; Jaiswal &amp; Ebert, 2019). \nPreliminary evidence suggests that after a perturbation such as cancer therapy, the composition of \nclones, which dominate the hematopoietic system, changes (Bolton, 2020). However, the studies \ncarried out until now have analysed CH at the population level, but little is known about the process at \nan individual level. Moreover, no study until now has addressed how perturbations of the systemic \nenvironment affect the clonal composition of blood at the single-cell level. \nCohort Description\nWe will take peripheral blood samples from 1 normal individual and 14 patients undergoing \nchemotherapy for the treatment of lymphoma with confirmed absence of bone marrow involvement. The \nchemotherapy-treated cohort will consist of 4 younger adults (aged under 55 years) and 8 older adults \n(aged over 70 years) who will all be receiving R- CHOP for treating diffuse large B-cell lymphoma as \nwell as 2 younger adults who are receiving a more intensive chemotherapy regimen such as BEACOPP \nor ABVD for the treatment of Hodgkin’s lymphoma. The described design will allow us to compare the \nresponse of the hematopoietic system at different ages to chemotherapy of different intensities, as well \nas provide a control to ensure longitudinal changes are not observed in normal, healthy individuals.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006152","title":"HSC_population_dynamics_in_perturbation___80M1_samples","description":"The aim of this project is to characterise how the systemic environment shapes the clonal landscape in \nadult humans and how perturbations affect this landscape. We are collecting longitudinal samples from \npatients before and after chemotherapy, in order to perform whole genome sequencing on their HSCs \nand, using patterns of shared and unique mutations, construct a phylogenetic tree of each patient’s \nHSCs. This will allow us to interrogate how clonal composition changes in response to chemotherapy, \nshedding insight into the fitness of mutations with respect to age and treatment.\nThe questions I want to answer: \n1. Are mutations that gave some HSCs an advantage, which resulted in their clonal expansion, still \nadvantageous in the new environment? Does chemotherapy favour some mutations over others? \n2. How do chemotherapies of different intensities affect the clonal landscape of HSCs? \n3. How does ageing affect the ability of the hematopoietic system to recover after chemotherapy? Are \nany clinical variables associated with improved recovery? \n4. Does the population of HSCs remain unchanged? \n5. How do different chemotherapies contribute to mutagenesis of HSCs?","abstract":"Background \nWith age, somatic mutations accumulate in normal dividing cells, including hematopoietic stem cells \n(HSCs). It appears that some mutations provide HSCs with a fitness advantage, allowing their mutant \ndaughter blood cells to disproportionately expand (Jaiswal &amp; Ebert, 2019). The phenomenon is termed \nclonal hematopoiesis (CH) and it is associated with ageing as well as hematologic malignancies, \ncardiovascular disease and all-cause mortality (Genovese et al., 2014; Jaiswal &amp; Ebert, 2019). \nPreliminary evidence suggests that after a perturbation such as cancer therapy, the composition of \nclones, which dominate the hematopoietic system, changes (Bolton, 2020). However, the studies \ncarried out until now have analysed CH at the population level, but little is known about the process at \nan individual level. Moreover, no study until now has addressed how perturbations of the systemic \nenvironment affect the clonal composition of blood at the single-cell level. \nCohort Description\nWe will take peripheral blood samples from 1 normal individual and 14 patients undergoing \nchemotherapy for the treatment of lymphoma with confirmed absence of bone marrow involvement. The \nchemotherapy-treated cohort will consist of 4 younger adults (aged under 55 years) and 8 older adults \n(aged over 70 years) who will all be receiving R- CHOP for treating diffuse large B-cell lymphoma as \nwell as 2 younger adults who are receiving a more intensive chemotherapy regimen such as BEACOPP \nor ABVD for the treatment of Hodgkin’s lymphoma. The described design will allow us to compare the \nresponse of the hematopoietic system at different ages to chemotherapy of different intensities, as well \nas provide a control to ensure longitudinal changes are not observed in normal, healthy individuals.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006153","title":"HSC_population_dynamics_in_perturbation___42F1_samples","description":"The aim of this project is to characterise how the systemic environment shapes the clonal landscape in \nadult humans and how perturbations affect this landscape. We are collecting longitudinal samples from \npatients before and after chemotherapy, in order to perform whole genome sequencing on their HSCs \nand, using patterns of shared and unique mutations, construct a phylogenetic tree of each patient’s \nHSCs. This will allow us to interrogate how clonal composition changes in response to chemotherapy, \nshedding insight into the fitness of mutations with respect to age and treatment.\nThe questions I want to answer: \n1. Are mutations that gave some HSCs an advantage, which resulted in their clonal expansion, still \nadvantageous in the new environment? Does chemotherapy favour some mutations over others? \n2. How do chemotherapies of different intensities affect the clonal landscape of HSCs? \n3. How does ageing affect the ability of the hematopoietic system to recover after chemotherapy? Are \nany clinical variables associated with improved recovery? \n4. Does the population of HSCs remain unchanged? \n5. How do different chemotherapies contribute to mutagenesis of HSCs?","abstract":"Background \nWith age, somatic mutations accumulate in normal dividing cells, including hematopoietic stem cells \n(HSCs). It appears that some mutations provide HSCs with a fitness advantage, allowing their mutant \ndaughter blood cells to disproportionately expand (Jaiswal &amp; Ebert, 2019). The phenomenon is termed \nclonal hematopoiesis (CH) and it is associated with ageing as well as hematologic malignancies, \ncardiovascular disease and all-cause mortality (Genovese et al., 2014; Jaiswal &amp; Ebert, 2019). \nPreliminary evidence suggests that after a perturbation such as cancer therapy, the composition of \nclones, which dominate the hematopoietic system, changes (Bolton, 2020). However, the studies \ncarried out until now have analysed CH at the population level, but little is known about the process at \nan individual level. Moreover, no study until now has addressed how perturbations of the systemic \nenvironment affect the clonal composition of blood at the single-cell level. \nCohort Description\nWe will take peripheral blood samples from 1 normal individual and 14 patients undergoing \nchemotherapy for the treatment of lymphoma with confirmed absence of bone marrow involvement. The \nchemotherapy-treated cohort will consist of 4 younger adults (aged under 55 years) and 8 older adults \n(aged over 70 years) who will all be receiving R- CHOP for treating diffuse large B-cell lymphoma as \nwell as 2 younger adults who are receiving a more intensive chemotherapy regimen such as BEACOPP \nor ABVD for the treatment of Hodgkin’s lymphoma. The described design will allow us to compare the \nresponse of the hematopoietic system at different ages to chemotherapy of different intensities, as well \nas provide a control to ensure longitudinal changes are not observed in normal, healthy individuals.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006154","title":"Detection of uniparental disomy from genome sequencing of family trio","description":"We created a bioinformatics pipeline to detect uniparental disomy from whole genome sequence data of family trios. We use inheritance patterns of single nucleotide polymorphisms to identify uniparental disomy events.","abstract":"We created a bioinformatics pipeline to detect uniparental disomy from whole genome sequence data of family trios. We use inheritance patterns of single nucleotide polymorphisms to identify uniparental disomy events.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-24T19:22:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006155","title":"Detection of maternal DNA contamination in the placenta","description":"We use whole-genome sequencing of monozygotic (and dizygotic) twins to detect somatic mutations to infer the cellular history of the twinning event. We recruited monozygotic twins with varying degrees of fetal membranes to compare the twinning events between theses subsets. We used blood, buccal epithelial cell, placenta, and umbilical cord to trace the embryonic somatic mutations. Using the somatic mutations from various tissues we infer the approximate timing of twinning in each monozygotic twin subtypes.","abstract":"We use whole-genome sequencing of monozygotic (and dizygotic) twins to detect somatic mutations to infer the cellular history of the twinning event. We recruited monozygotic twins with varying degrees of fetal membranes to compare the twinning events between theses subsets. We used blood, buccal epithelial cell, placenta, and umbilical cord to trace the embryonic somatic mutations. Using the somatic mutations from various tissues we infer the approximate timing of twinning in each monozygotic twin subtypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-24T21:55:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006156","title":"HCA_Thymus_Paediatric_CZI_Spatial","description":"Spatial transcriptome analysis of thymic cells from children with syndromic diseases such as Trisomy 21 and inflammatory/autoimmune diseases such as myasthenia gravis.","abstract":"Spatial transcriptome analysis of thymic cells from children with syndromic diseases such as Trisomy 21 and inflammatory/autoimmune diseases such as myasthenia gravis. Our group has previously performed atlasing of the healthy human thymus using single cell transcriptomics and obtained an unprecedented understanding of human thymus throughout development. In this study, we intend to survey diseased human thymus and compare this to healthy to obtain a better understanding of thymic dysfunction in human diseases. The diseases we will survey include congenital conditions such as Down's syndrome, CHARGE syndrome, DiGeorge syndrome as well as acquired diseases such as myasthenia gravis and thymic hyperplasia. We intend to perform genetic and genomic study on the samples, including expression analysis. This will not only help us to understand the cells and molecular pathways affected in dysfunctional thymus; but may also lead to generalisable understandings in human genetic diseases and inflammatory/autoimmune diseases. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-25T10:35:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006157","title":"miRNA regulation of monocyte expressed inflammatory genes in patients with inflammatory bowel disease","description":null,"abstract":"MicroRNAs are critical regulators of gene expression controlling cellular processes including inflammation. We explored their role in the pathogenesis of inflammatory bowel disease (IBD), and identified reduced expression of miR-374a-5p in IBD monocytes that correlated with a module of up- regulated genes related to the inflammatory response.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-25T15:54:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006158","title":"Exome sequencing in CLL re-treated with venetoclax","description":null,"abstract":"The aim of this study was to identify mutational and genetic drivers of sensitivity and resistance to venetoclax and BCR inhibitors. Sequential samples were used to track the variant allele frequencies of driver mutations and copy number alterations. These were used to infer sub-clonal architecture through sequential therapies.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-26T19:24:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006159","title":"Epigenomic data of Human muscle stem cell","description":"To profile the epigenomic landscape of Human muscle stem cell, ChIP-seq of histone marks , WGBS and RNA-seq data were generated.","abstract":"To profile the epigenomic landscape of Human muscle stem cell, ChIP-seq of histone marks , WGBS and RNA-seq data were generated.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-28T08:03:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006160","title":"HCA_Lung_Adult_discovAIR_DNA","description":"WSSS Deep Dive for Adult Lung DNA only. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Human Cell Atlas for lung - Adult DNA work. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006161","title":"Enhancer profiling to identify identifies epigenetic markers of endocrine resistance in metastatic castration resistant prostate cancer patients","description":null,"abstract":"Using fresh-frozen metastatic samples from mCRPC patients enrolled in a phase II clinical trial, collected prior and post to androgen receptor (AR) targeted therapy, we epigenetically profiled enhancer and promoter activity using H3K27ac chromatin immunoprecipitation sequencing to identify regions which enable response prediction. These regions were further queried for association with specific candidate factors that drive resistance to hormonal suppression revealing new therapeutic options for mCRPC patients.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-28T10:12:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006162","title":"ALK inhibitor resistance - preclinical","description":null,"abstract":"Study of resistance to ALK inhibition in neuroblastoma - cell one data","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006163","title":"ALK inhibitor resistance - clinical","description":null,"abstract":"Study of the mechanisms of resistance to ALK inhibition in neuroblastoma.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006164","title":"Validation of a targeted sequencing panel for multiple myeloma","description":null,"abstract":"Here we provide a validated panel for targeted sequencing and analysis of myeloma and other plasma cell dyscrasias to identify the common genomic abnormalities that are diagnostic, prognostic, and clinically actionable. This panel can identify the common immunoglobulin translocations and copy number abnormalities currently detected by FISH, as well as less common translocations, MYC rearrangements, and mutations that are not currently tested for in a standard manner. We hope that adoption of a common sequencing panel will improve patient diagnostics and can be used to assist in risk stratification at diagnosis or post-treatment to guide therapeutic decision making.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-29T17:50:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006165","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__gall_bladder","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, head and neck, bladder, gall bladder, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"he Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, head and neck, bladder, gall bladder, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006166","title":"Molecular landscape of blastic plasmacytoid dendritic cell neoplasm","description":"Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive malignancy assumed to originate from plasmacytoid dendritic cells (pDCs), which mostly affects the skin, bone marrow and lymph nodes and sequentially other organ systems. We applied paired WES/RNA-seq combined with genome-wide copy-number analysis to characterize 47 BPDCN patients regarding mutational drivers, cytogenetic aberrations and gene-expression profiles.","abstract":"Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive malignancy assumed to originate from plasmacytoid dendritic cells (pDCs), which mostly affects the skin, bone marrow and lymph nodes and sequentially other organ systems. We applied paired WES/RNA-seq combined with genome-wide copy-number analysis to characterize 47 BPDCN patients regarding mutational drivers, cytogenetic aberrations and gene-expression profiles.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-30T14:09:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006167","title":"LCM-ATACseq on human lung macrophages","description":"In this study we employed Laser Capture Microdissection (LCM) for the multimodal profiling of lung macrophages cell populations as a function of location within the healthy tissue. In detail, macrophage mini-bulks (~100 cells) were collected from 4 healthy human donors in 5 different locations of the airways (a total of 20 biopsies), including parenchyma (L1 – lower left lobe (LLL); L6 – 80% distance from LLL tip), trachea (L2), bronchi (L3 – 1st/2nd generation; L5 – 3rd/4th generation), and processed for ATAC-seq.","abstract":"In this study we employed Laser Capture Microdissection (LCM) for the multimodal profiling of lung macrophages cell populations as a function of location within the healthy tissue. In detail, macrophage mini-bulks (~100 cells) were collected from 4 healthy human donors in 5 different locations of the airways (a total of 20 biopsies), including parenchyma (L1 – lower left lobe (LLL); L6 – 80% distance from LLL tip), trachea (L2), bronchi (L3 – 1st/2nd generation; L5 – 3rd/4th generation), and processed for ATAC-seq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-30T14:41:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006168","title":"LCM-RNAseq on human lung macrophages","description":"In the reported study, we employed Laser Capture Microdissection (LCM) for the transcriptome profiling of lung macrophages cells populations as a function of location within the healthy tissue. In detail, macrophage mini-bulks (100 cells each) were collected by LCM from 4 healthy human donors in 5 different locations of the airways (a total of 20 biopsies), including parenchyma (L1 – lower left lobe (LLL); L6 – 80% distance from LLL tip), trachea (L2), bronchi (L3 – 1st/2nd generation; L5 – 3rd/4th generation) and processed for RNA-seq.","abstract":"In the reported study, we employed Laser Capture Microdissection (LCM) for the transcriptome profiling of lung macrophages cells populations as a function of location within the healthy tissue. In detail, macrophage mini-bulks (100 cells each) were collected by LCM from 4 healthy human donors in 5 different locations of the airways (a total of 20 biopsies), including parenchyma (L1 – lower left lobe (LLL); L6 – 80% distance from LLL tip), trachea (L2), bronchi (L3 – 1st/2nd generation; L5 – 3rd/4th generation) and processed for RNA-seq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-30T14:41:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006169","title":"Res1_PC9_exp1_MC_29_03_22","description":"8 cell pellet samples for genomic DNA extraction.\nCRISPR PCR1 and PCR2 indexing - Please use standard Kosuke primers.","abstract":"8 cell pellet samples for genomic DNA extraction.\nCRISPR PCR1 and PCR2 indexing - Please use standard Kosuke primers.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-30T15:21:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006170","title":"Res1_PC9_exp2_MC_01_04_22","description":"8 cell pellet samples for genomic DNA extraction.\nCRISPR PCR1 and PCR2 indexing - Please use standard Kosuke primers.","abstract":"8 cell pellet samples for genomic DNA extraction.\nCRISPR PCR1 and PCR2 indexing - Please use standard Kosuke primers.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-30T15:31:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006171","title":"The cell free DNA methylome of primary and metastatic prostate tumors -- CRPC samples, VPC","description":"Metastatic prostate cancer remains a major clinical challenge. Liquid biopsy is emerging as a promising tool in disease management and provides valuable opportunities to gain insights into the underlying biology. Here, we used the highly sensitive, methylated DNA immunoprecipitation coupled to next generation sequencing (MeDIP) technology, to interrogate the cell-free DNA methylomes across localized and metastatic prostate cancer.","abstract":"Metastatic prostate cancer remains a major clinical challenge. Liquid biopsy is emerging as a promising tool in disease management and provides valuable opportunities to gain insights into the underlying biology. Here, we used the highly sensitive, methylated DNA immunoprecipitation coupled to next generation sequencing (MeDIP) technology, to interrogate the cell-free DNA methylomes across localized and metastatic prostate cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006172","title":"A Dose Escalation Study of Efmarodocokin Alfa (UTTR1147A) in Healthy Volunteers and Patients with Ulcerative Colitis","description":"Background: The interleukin-22 cytokine (IL-22) has demonstrated efficacy in nonclinical colitis models with a non-immunosuppressive mechanism-of-action. Efmarodocokin alfa (UTTR1147A) is a fusion protein agonist that links IL-22 to the crystallizable fragment (Fc) of human immunoglobulin (IgG4) for improved pharmacokinetic characteristics, but with a mutation to minimize Fc effector functions.\nMethods: This randomized, phase 1b study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of repeat intravenous dosing of efmarodocokin alfa in healthy volunteers (HVs; n=32) and patients with ulcerative colitis (UC; n=24) at 30–90 µg/kg doses given biweekly (Q2W) or monthly (Q4W) (6:2 active:placebo per cohort).\nResults: The most common adverse events (AEs) were on-target dermatological effects (dry skin, erythema, and pruritus) that were reversible. Dose-limiting non-serious dermatological AEs (severe dry skin, erythema, exfoliation, and discomfort) were seen in two HVs and one patient at 90 ug/kg Q2W. Pharmacokinetics were generally dose-proportional across the dose levels tested, but patients demonstrated lower drug exposures relative to HVs at the same dose. IL-22 serum biomarkers and IL-22 responsive genes in colon biopsies were induced with active treatment. Patients demonstrated changes in microbiota composition following active treatment, thereby reversing baseline dysbiosis. Clinical response was observed in 7/18 active- and 1/6 placebo-treated patients; clinical remission was observed in 5/18 active- and 0/6 placebo-treated patients.","abstract":"Background: The interleukin-22 cytokine (IL-22) has demonstrated efficacy in nonclinical colitis models with a non-immunosuppressive mechanism-of-action. Efmarodocokin alfa (UTTR1147A) is a fusion protein agonist that links IL-22 to the crystallizable fragment (Fc) of human immunoglobulin (IgG4) for improved pharmacokinetic characteristics, but with a mutation to minimize Fc effector functions.\nMethods: This randomized, phase 1b study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of repeat intravenous dosing of efmarodocokin alfa in healthy volunteers (HVs; n=32) and patients with ulcerative colitis (UC; n=24) at 30–90 µg/kg doses given biweekly (Q2W) or monthly (Q4W) (6:2 active:placebo per cohort).\nResults: The most common adverse events (AEs) were on-target dermatological effects (dry skin, erythema, and pruritus) that were reversible. Dose-limiting non-serious dermatological AEs (severe dry skin, erythema, exfoliation, and discomfort) were seen in two HVs and one patient at 90 ug/kg Q2W. Pharmacokinetics were generally dose-proportional across the dose levels tested, but patients demonstrated lower drug exposures relative to HVs at the same dose. IL-22 serum biomarkers and IL-22 responsive genes in colon biopsies were induced with active treatment. Patients demonstrated changes in microbiota composition following active treatment, thereby reversing baseline dysbiosis. Clinical response was observed in 7/18 active- and 1/6 placebo-treated patients; clinical remission was observed in 5/18 active- and 0/6 placebo-treated patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-31T00:47:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006173","title":"Phase 1 CX-5461 Trial (Canadian Cancer Trials Group Trial IND.231)","description":"CX-5461 is a G-quadruplex stabilizer that exhibits synthetic lethality in homologous recombination (HR) deficient models. In this multicentre Phase Ib trial in patients with solid tumors, 40 patients were treated across 10 dose levels (50 - 650 mg/m2) to determine the recommended phase II dose (RP2D), and evaluate safety, tolerability, pharmacokinetics. Defective HR was explored as a predictive biomarker. CX-5461 was generally well tolerated, with a RP2D of 475 mg/m2 d1, 8 and 15 every 4 weeks, and dose limiting toxicities of phototoxicity. Responses were observed in 10% of patients, primarily in patients with defective HR (ORR 14%). Reversion mutations in PALB2 and BRCA2 were detected on progression following initial response in germline carriers, confirming the underlying synthetic lethal mechanism. In vitro characterization of UV sensitization showed this toxicity is related to the CX-5461 chemotype, independent of G4 synthetic lethality. These results establish clinical proof-of-concept for this first-in class G4 stabilizer.","abstract":"CX-5461 is a G-quadruplex stabilizer that exhibits synthetic lethality in homologous recombination (HR) deficient models. In this multicentre Phase Ib trial in patients with solid tumors, 40 patients were treated across 10 dose levels (50 - 650 mg/m2) to determine the recommended phase II dose (RP2D), and evaluate safety, tolerability, pharmacokinetics. Defective HR was explored as a predictive biomarker. CX-5461 was generally well tolerated, with a RP2D of 475 mg/m2 d1, 8 and 15 every 4 weeks, and dose limiting toxicities of phototoxicity. Responses were observed in 10% of patients, primarily in patients with defective HR (ORR 14%). Reversion mutations in PALB2 and BRCA2 were detected on progression following initial response in germline carriers, confirming the underlying synthetic lethal mechanism. In vitro characterization of UV sensitization showed this toxicity is related to the CX-5461 chemotype, independent of G4 synthetic lethality. These results establish clinical proof-of-concept for this first-in class G4 stabilizer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-31T18:39:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006174","title":"Small molecule inhibitors of LOXL synergize with 5-AZA to restore erythropoiesis in myeloid neoplasms","description":"Objectives: Bone marrow (BM) stroma and microenvironmental factors in the BM milieu of myeloid neoplasms are increasingly being recognized as novel perspective therapeutic targets. Lysyl oxidases (LOX/LOXL) are crucial enzymes that cross-link collagen and contribute to the deposition of aberrant stiff extracellular matrix (ECM) in the BM of patients with myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). Here, we studied whether inhibition of LOX/LOXL enzymes produced by BM-derived MSCs favors the differentiation of MDS/MPN hematopoietic stem cell and progenitor cells (HPSCs) and enhances the effects of 5-azacytidine (5-AZA).\n\nMethods: Primary co-cultures of MSCs and HPSCs were established from n=31 MDS/MPN patients and treated with the pan-LOX/LOXL inhibitor PXS-5505, 5-AZA or the combination of both for 4 days. At the end of co-culture, HSPC differentiation was assessed by CFU assays and flow cytometry. In some of the experiments, MSCs monolayers were pre-treated or not with PXS-5505 for 6 days and decellularized using 20 mM ammonia. Subsequently, autologous HSPCs were cultured on ECM matrices in the presence of 5-AZA or PXS-5505 + 5-AZA combination with or without inhibitors of integrin signaling such as blebbistatin, Y-27632 and αvβ3-integrin blocking antibodies. Patient-derived xenografts (PDX) were established in NSG mice based on intrafemoral co-injection of HSPCs and autologous MSCs. PDX were treated with 3 cycles of 5-AZA (75 mg/m2), PXS-5505 (30 mg/kg on alternate days for the duration of 5-AZA treatment) or combination of both.\n\nResults: MSCs of MDS and MPN patients displayed significant overexpression of LOX/LOXL transcripts as compared to healthy age-matched controls. Remarkably, LOX/LOXL inhibition in MSCs/HSPCs co-cultures increased erythroid differentiation of patient HSPCs that had suboptimal or no response to 5-AZA alone. From a total of n=31 advanced stage MDS/MPN patients, n=11 (35.5%) responded to the combination treatment, which was evidenced by a significant increase of CD235a+CD45- erythroid cell production compared to 5-AZA/PXS/untreated arms (p&lt;0.05). Of note, combination treatment with 5-AZA + PXS-5505 facilitated differentiation of CD235+ erythroid progenitors from HSPCs sub-clones with low mutational VAFs. The presence of MSCs was necessary for the effects of the combination treatment and required direct cell contacts between MSCs and HSPCs. Moreover, PXS-5505-mediated alterations of the ECM composition alone were sufficient to induce erythroid\n\ndifferentiation. Inhibition of integrin-mediated signaling using blebbistatin, Y-27632 and αvβ3-integrin antibodies completely abrogated the effects of PXS-5505 induced erythroid differentiation. In vivo, the combination of PXS-5505 + 5-AZA favored erythroid differentiation of HSPCs and confirmed the in-vitro results. The combination treatment of 5-AZA + PXS-5505 induced the greatest reduction of disease burden as assessed by decrease of spleen indexes, total engraftment rates, BM fibrosis and mutational VAF profiles.\n\nConclusions: The combination of 5-AZA + LOX/LOXL inhibitor PXS-5505 in MDS and MPN synergistically restores erythropoietic differentiation of primary HSPCs. The effect is dependent of contact interaction between HSPCs and niche components, such as MSCs and MSCs-derived ECM. Our data propose a strong rationale for a BM niche targeted combination treatment with 5-AZA + PXS-5505 in transfusion dependent MDS and MPN, which will be assessed in forthcoming clinical trials.","abstract":"Objectives: Bone marrow (BM) stroma and microenvironmental factors in the BM milieu of myeloid neoplasms are increasingly being recognized as novel perspective therapeutic targets. Lysyl oxidases (LOX/LOXL) are crucial enzymes that cross-link collagen and contribute to the deposition of aberrant stiff extracellular matrix (ECM) in the BM of patients with myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). Here, we studied whether inhibition of LOX/LOXL enzymes produced by BM-derived MSCs favors the differentiation of MDS/MPN hematopoietic stem cell and progenitor cells (HPSCs) and enhances the effects of 5-azacytidine (5-AZA).\n\nMethods: Primary co-cultures of MSCs and HPSCs were established from n=31 MDS/MPN patients and treated with the pan-LOX/LOXL inhibitor PXS-5505, 5-AZA or the combination of both for 4 days. At the end of co-culture, HSPC differentiation was assessed by CFU assays and flow cytometry. In some of the experiments, MSCs monolayers were pre-treated or not with PXS-5505 for 6 days and decellularized using 20 mM ammonia. Subsequently, autologous HSPCs were cultured on ECM matrices in the presence of 5-AZA or PXS-5505 + 5-AZA combination with or without inhibitors of integrin signaling such as blebbistatin, Y-27632 and αvβ3-integrin blocking antibodies. Patient-derived xenografts (PDX) were established in NSG mice based on intrafemoral co-injection of HSPCs and autologous MSCs. PDX were treated with 3 cycles of 5-AZA (75 mg/m2), PXS-5505 (30 mg/kg on alternate days for the duration of 5-AZA treatment) or combination of both.\n\nResults: MSCs of MDS and MPN patients displayed significant overexpression of LOX/LOXL transcripts as compared to healthy age-matched controls. Remarkably, LOX/LOXL inhibition in MSCs/HSPCs co-cultures increased erythroid differentiation of patient HSPCs that had suboptimal or no response to 5-AZA alone. From a total of n=31 advanced stage MDS/MPN patients, n=11 (35.5%) responded to the combination treatment, which was evidenced by a significant increase of CD235a+CD45- erythroid cell production compared to 5-AZA/PXS/untreated arms (p&lt;0.05). Of note, combination treatment with 5-AZA + PXS-5505 facilitated differentiation of CD235+ erythroid progenitors from HSPCs sub-clones with low mutational VAFs. The presence of MSCs was necessary for the effects of the combination treatment and required direct cell contacts between MSCs and HSPCs. Moreover, PXS-5505-mediated alterations of the ECM composition alone were sufficient to induce erythroid\n\ndifferentiation. Inhibition of integrin-mediated signaling using blebbistatin, Y-27632 and αvβ3-integrin antibodies completely abrogated the effects of PXS-5505 induced erythroid differentiation. In vivo, the combination of PXS-5505 + 5-AZA favored erythroid differentiation of HSPCs and confirmed the in-vitro results. The combination treatment of 5-AZA + PXS-5505 induced the greatest reduction of disease burden as assessed by decrease of spleen indexes, total engraftment rates, BM fibrosis and mutational VAF profiles.\n\nConclusions: The combination of 5-AZA + LOX/LOXL inhibitor PXS-5505 in MDS and MPN synergistically restores erythropoietic differentiation of primary HSPCs. The effect is dependent of contact interaction between HSPCs and niche components, such as MSCs and MSCs-derived ECM. Our data propose a strong rationale for a BM niche targeted combination treatment with 5-AZA + PXS-5505 in transfusion dependent MDS and MPN, which will be assessed in forthcoming clinical trials.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-03-31T20:32:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006175","title":"Characterization of Cell Free Plasma Methyl-DNA From Xenografted Tumors to Guide the Selection of Diagnostic Markers for Early-Stage Cancers","description":"Circulating cell-free methyl-DNA (mcfDNA) contains promising cancer markers but its low abundance and possibly diverse origin pose challenges toward the accurate diagnosis of early stage cancers. By whole-genome bisulfite sequencing (WGBS) of cell-free DNA (cfDNA) from about 0.5 mL plasma of mice xenografted with human tumors, we obtained and aligned the reads to the human genome, filtered out the mouse and carrier bacterial sequences, and confirmed the tumor origin of methyl-cfDNA (mctDNA) by methylation-sensitive restriction enzyme digestion prior to species-specific PCR. We estimated that human tumor-specific reads (ctDNA) or mctDNA comprised about 0.29 or 0.01%, respectively of the xenograft mouse cfDNA, and about 0.029 or 0.001% of the cfDNA of human early stage cancer patients. Similar WGBS of early stage (0-II, node- and metastasis-free) breast, lung or colorectal cancer samples identified hundreds of specific DMRs (differentially methylated regions) compared to healthy controls. Their association with tumourigenesis was supported by stage-dependent methylation, tumor suppressor or oncogene clusters, and genes also identified in the xenograft samples. Using 20 three-cancer-common and 17 colorectal cancer-specific DMRs in combination (top 0.0018% of the WGBS methylation clusters) was sufficient to distinguish the stage I colorectal cancers from breast and lung cancers and healthy controls. Our data thus confirmed the tumor origin of mctDNA by sequence specificity, and provide a selection threshold for authentic tumor mctDNA markers toward precise diagnosis of early stage cancers solely by top DMRs in combination.\n\nBiological Materials were provided by the Ontario Tumour Bank, which is funded by the Ontario Institute for Cancer Research\n\nReference for citation: Ling Liu, Jinghua Feng, Julian Polimeni, Manli Zhang, Hai Nguyen, Urmi Das, Xu Zhang, Harminder Singh, Xiao-Jian Yao, Etienne Leygue, Sam K.P. Kung, and Xie J. Characterization of cell free plasma methyl-DNA from xenografted tumours to guide the selection of diagnostic markers for early-stage cancers. Frontiers in Oncology, 2021 Feb. 5. DOI: 10.3389/fonc.2021.615821.","abstract":"Circulating cell-free methyl-DNA (mcfDNA) contains promising cancer markers but its low abundance and possibly diverse origin pose challenges toward the accurate diagnosis of early stage cancers. By whole-genome bisulfite sequencing (WGBS) of cell-free DNA (cfDNA) from about 0.5 mL plasma of mice xenografted with human tumors, we obtained and aligned the reads to the human genome, filtered out the mouse and carrier bacterial sequences, and confirmed the tumor origin of methyl-cfDNA (mctDNA) by methylation-sensitive restriction enzyme digestion prior to species-specific PCR. We estimated that human tumor-specific reads (ctDNA) or mctDNA comprised about 0.29 or 0.01%, respectively of the xenograft mouse cfDNA, and about 0.029 or 0.001% of the cfDNA of human early stage cancer patients. Similar WGBS of early stage (0-II, node- and metastasis-free) breast, lung or colorectal cancer samples identified hundreds of specific DMRs (differentially methylated regions) compared to healthy controls. Their association with tumourigenesis was supported by stage-dependent methylation, tumor suppressor or oncogene clusters, and genes also identified in the xenograft samples. Using 20 three-cancer-common and 17 colorectal cancer-specific DMRs in combination (top 0.0018% of the WGBS methylation clusters) was sufficient to distinguish the stage I colorectal cancers from breast and lung cancers and healthy controls. Our data thus confirmed the tumor origin of mctDNA by sequence specificity, and provide a selection threshold for authentic tumor mctDNA markers toward precise diagnosis of early stage cancers solely by top DMRs in combination.\n\nBiological Materials were provided by the Ontario Tumour Bank, which is funded by the Ontario Institute for Cancer Research\n\nReference for citation: Ling Liu, Jinghua Feng, Julian Polimeni, Manli Zhang, Hai Nguyen, Urmi Das, Xu Zhang, Harminder Singh, Xiao-Jian Yao, Etienne Leygue, Sam K.P. Kung, and Xie J. Characterization of cell free plasma methyl-DNA from xenografted tumours to guide the selection of diagnostic markers for early-stage cancers. Frontiers in Oncology, 2021 Feb. 5. DOI: 10.3389/fonc.2021.615821.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-01T02:13:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006176","title":"Genomic insights into the population history of the Resande or Swedish Travellers","description":null,"abstract":"In the present work we analyze for the first time from a genetic perspective the Resande population, a minority ethnic group from Sweden that has been scarcely studied and historically persecuted. We studied their origins and demographic history by using genome-wide array data and whole mitochondrial sequences.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-01T12:09:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006177","title":"Kidney_Tumour_Extension_Exome_DNA","description":"We propose to build a genetic knowledge bank of Wilms tumour that integrates clinical outcome data with a genetic, epigenetic, and transcriptomic survey of 1,000 Wilms tumours.","abstract":"The purpose of the knowledge bank is to serve as a community resource and to address the following specific questions about Wilms tumour: (1) Do genetic, epigenetic, or transcriptional features predict outcome and thus lend themselves to treatment stratification? (2) What are the genetic drivers of Wilms tumour, considering the entire histological spectrum of Wilms tumour including the most common subtypes classified as intermediate risk?","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006178","title":"Kidney_Tumour_Extension_Exome_RNA","description":"We propose to build a genetic knowledge bank of Wilms tumour that integrates clinical outcome data with a genetic, epigenetic, and transcriptomic survey of 1,000 Wilms tumours.","abstract":"The purpose of the knowledge bank is to serve as a community resource and to address the following specific questions about Wilms tumour: (1) Do genetic, epigenetic, or transcriptional features predict outcome and thus lend themselves to treatment stratification? (2) What are the genetic drivers of Wilms tumour, considering the entire histological spectrum of Wilms tumour including the most common subtypes classified as intermediate risk?","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006179","title":"Tumor Evolution in Small Cell Lung Cancer","description":null,"abstract":"Small cell lung cancer (SCLC) is a highly aggressive tumor that accounts for 15% of all lung cancers. SCLC patients are commonly diagnosed at a late stage, which complicates surgical resections. Therefore, the current standard of care is a platinum-based chemotherapy, and recently a combination with anti-PD-L1 therapy . SCLC patients initially respond well to this treatment, but quickly relapse with a therapy-resistant tumor. Targeted therapies have not been identified, which leaves no other effective treatment options. The clinical performance quickly deteriorates at the time of relapse, resulting in a poor 5-year overall survival rate of less than 2%.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006180","title":"Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis","description":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","abstract":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006181","title":"The BC Cancer Agency's Personalized Onco-Genomics Project","description":null,"abstract":"The BC Cancer Agency's Personalized Onco-Genomics (POG) Project involves molecular and clinical characterization of individual cancer patients to guide their treatment. The project aims to use whole genome and transcriptome data together with patient information to match treatments to cancer driver alterations and support clinical decision-making. Incorporating genomic data into decision-making should enable more rational development of treatment plans, facilitate enrollment into appropriate clinical trials and potentially identify less toxic and more effective therapeutic options.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006182","title":"Study title","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006183","title":"Study title","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006184","title":"Mapping genetic effects on cell type-specific chromatin accessibility using single nucleus ATAC-seq","description":"Gene regulation is highly cell type-specific and understanding the function of non-coding genetic variants associated with complex traits requires molecular phenotyping at cell type resolution. In this study we performed single nucleus ATAC-seq (snATAC-seq) and genotyping in peripheral blood mononuclear cells from 13 individuals. We mapped chromatin accessibility QTLs (caQTLs) in each immune cell type and sub-type in a subset of 10 samples of European genetic ancestry.","abstract":"Gene regulation is highly cell type-specific and understanding the function of non-coding genetic variants associated with complex traits requires molecular phenotyping at cell type resolution. In this study we performed single nucleus ATAC-seq (snATAC-seq) and genotyping in peripheral blood mononuclear cells from 13 individuals. We mapped chromatin accessibility QTLs (caQTLs) in each immune cell type and sub-type in a subset of 10 samples of European genetic ancestry.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-05T01:20:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006185","title":"Variants from a subset of genes from WES of adult AML patient samples","description":"The aim if this study was to identify variants in a specific list of genes in samples from adult AML patients. The gene list includes DNA repair and mitochondrial respiratory chain genes.","abstract":"The aim if this study was to identify variants in a specific list of genes in samples from adult AML patients. The gene list includes DNA repair and mitochondrial respiratory chain genes.","study_type":"Other","pubmed_ids":[29891941],"external_links":null,"is_released":true,"released_date":"2022-04-05T03:07:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006186","title":"Dual spatially resolved transcriptomics for human host-pathogen colocalization studies in FFPE tissue sections","description":"Technologies to study localized host-pathogen interactions are urgently needed. Here, we present a spatial transcriptomics approach to simultaneously capture host and pathogen transcriptome-wide spatial gene expression information from human formalin-fixed paraffin-embedded (FFPE) tissue sections at a near single-cell resolution. We demonstrate this methodology in lung samples from COVID-19 patients and validate our spatial detection of SARS-CoV-2 against RNAScope and in situ sequencing. Host-pathogen colocalization analysis identified putative modulators of SARS-CoV-2 infection in human lung cells. Our approach provides new insights into host response to pathogen infection through the simultaneous, unbiased detection of two transcriptomes in FFPE samples.","abstract":"Technologies to study localized host-pathogen interactions are urgently needed. Here, we present a spatial transcriptomics approach to simultaneously capture host and pathogen transcriptome-wide spatial gene expression information from human formalin-fixed paraffin-embedded (FFPE) tissue sections at a near single-cell resolution. We demonstrate this methodology in lung samples from COVID-19 patients and validate our spatial detection of SARS-CoV-2 against RNAScope and in situ sequencing. Host-pathogen colocalization analysis identified putative modulators of SARS-CoV-2 infection in human lung cells. Our approach provides new insights into host response to pathogen infection through the simultaneous, unbiased detection of two transcriptomes in FFPE samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-05T06:52:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006187","title":"Case Report: Precision medicine target revealed by in-vitro modelling of relapsed, refractory ALL from a child with neurofibromatosis","description":"Children with neurofibromatosis have a higher risk of developing juvenile myelomonocytic leukaemia and acute myeloid leukaemia, but rarely develop B-cell acute lymphoblastic leukaemia (B-ALL). Through in-vitro modelling, a novel NF1 p.L2467 frameshift (fs) mutation identified in a relapsed/refractory Ph-like B-ALL patient with neurofibromatosis demonstrated cytokine independence and increased RAS signalling, indicative of leukaemic transformation. Furthermore, these cells were sensitive to the MEK inhibitors trametinib and mirdametinib. Bi-allelic NF1 loss of function may be a contributing factor to relapse and with sensitivity to MEK inhibitors, suggests a novel precision medicine target in the setting of neurofibromatosis patients with B-ALL.","abstract":"Children with neurofibromatosis have a higher risk of developing juvenile myelomonocytic leukaemia and acute myeloid leukaemia, but rarely develop B-cell acute lymphoblastic leukaemia (B-ALL). Through in-vitro modelling, a novel NF1 p.L2467 frameshift (fs) mutation identified in a relapsed/refractory Ph-like B-ALL patient with neurofibromatosis demonstrated cytokine independence and increased RAS signalling, indicative of leukaemic transformation. Furthermore, these cells were sensitive to the MEK inhibitors trametinib and mirdametinib. Bi-allelic NF1 loss of function may be a contributing factor to relapse and with sensitivity to MEK inhibitors, suggests a novel precision medicine target in the setting of neurofibromatosis patients with B-ALL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-05T16:05:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006188","title":"5' Single cell RNA sequencing of pre-treatment tissues from lung cancer patients receiving immunotherapy","description":null,"abstract":"We performed single-cell RNA sequencing (scRNA-seq) for 96,505 cells derived from 33 pre-treatment fresh tissues from 26 lung cancer patients. Most of the samples were collected from lymph nodes, followed by bronchus, lung, brain, liver, and pleural effusion. The extensive single cell profiles delineated the tumor-intrinsic properties and immune cell dynamics associated with immune checkpoint inhibitor responses.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006189","title":"3' Single cell RNA sequencing of pre-treatment tissues from lung cancer patients receiving immunotherapy","description":null,"abstract":"We performed single-cell RNA sequencing (scRNA-seq) for 96,505 cells derived from 33 pre-treatment fresh tissues from 26 lung cancer patients. Most of the samples were collected from lymph nodes, followed by bronchus, lung, brain, liver, and pleural effusion. The extensive single cell profiles delineated the tumor-intrinsic properties and immune cell dynamics associated with immune checkpoint inhibitor responses.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006190","title":"SWeet treat index in finnish children","description":null,"abstract":"Excess sugar consumption is common among youth and can have adverse health effects. However, the relationship between saliva microbiota and sugar consumption remains sparsely studied. We aimed to explore diversity, composition and functional capacities of saliva microbiota in 11–13-year-old Finnish children with low and high sweet treat consumption.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006191","title":"Molecular and clinical diversity in primary central nervous system lymphoma: a LOC Network study","description":"Primary central nervous system lymphoma (PCNSL) is a distinct extranodal lymphoma presenting with limited stage disease but variable response rates to treatment despite homogenous pathological presentation. The likely underlying molecular heterogeneity and its clinical impact is poorly understood.\nWe performed a comprehensive genome-wide analysis of 147 PCNSL from fresh-frozen tumor tissue from immunocompetent, treatment naïve PCNSL patients, employing whole-exome sequencing, assessment of somatic copy number alterations and DNA methylation, and RNA expression. These data were integrated and correlated with the clinico-radiological characteristics and outcomes of the patients. We validated our results in an independent series of 93 PCNSL formalin-fixed, paraffin-embedded (FFPE) samples.\nConsensus clustering of multi-omics data identified four robust, non-overlapping, prognostically significant clusters (CS) within PCNSL. The CS1 group, characterized by high proliferation and Polycomb Repressive Complex 2 (PRC2) complex activity had an intermediate outcome between CS2/CS3 and CS4. Patients who had PCNSL with an “immune-hot” (CS4) profile had the most favorable clinical outcome. In contrast, patients with the immune-cold hypermethylated CS2 and the heterogenous-immune CS3 groups had a poor prognosis. Nearly all PCNSL patients with meningeal infiltration harbored HIST1H1E mutations, enriched in the CS3 group. The integrated analysis suggests that the CS4 group may be more susceptible to immunotherapy.\tThe integration of genome-wide data from multi-omics data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that significantly improved the current clinical stratification. This molecular classification using FFPE samples facilitates routine use in clinical practice and provides potential precision-medicine strategies in PCNSL.","abstract":"Primary central nervous system lymphoma (PCNSL) is a distinct extranodal lymphoma presenting with limited stage disease but variable response rates to treatment despite homogenous pathological presentation. The likely underlying molecular heterogeneity and its clinical impact is poorly understood.\nWe performed a comprehensive genome-wide analysis of 147 PCNSL from fresh-frozen tumor tissue from immunocompetent, treatment naïve PCNSL patients, employing whole-exome sequencing, assessment of somatic copy number alterations and DNA methylation, and RNA expression. These data were integrated and correlated with the clinico-radiological characteristics and outcomes of the patients. We validated our results in an independent series of 93 PCNSL formalin-fixed, paraffin-embedded (FFPE) samples.\nConsensus clustering of multi-omics data identified four robust, non-overlapping, prognostically significant clusters (CS) within PCNSL. The CS1 group, characterized by high proliferation and Polycomb Repressive Complex 2 (PRC2) complex activity had an intermediate outcome between CS2/CS3 and CS4. Patients who had PCNSL with an “immune-hot” (CS4) profile had the most favorable clinical outcome. In contrast, patients with the immune-cold hypermethylated CS2 and the heterogenous-immune CS3 groups had a poor prognosis. Nearly all PCNSL patients with meningeal infiltration harbored HIST1H1E mutations, enriched in the CS3 group. The integrated analysis suggests that the CS4 group may be more susceptible to immunotherapy.\tThe integration of genome-wide data from multi-omics data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that significantly improved the current clinical stratification. This molecular classification using FFPE samples facilitates routine use in clinical practice and provides potential precision-medicine strategies in PCNSL.","study_type":"Other","pubmed_ids":[36402300],"external_links":null,"is_released":true,"released_date":"2022-04-06T14:23:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006192","title":"The cell free DNA methylome of primary and metastatic prostate tumors -- CRPC samples, Barrier","description":"Metastatic prostate cancer remains a major clinical challenge. Liquid biopsy is emerging as a promising tool in disease management and provides valuable opportunities to gain insights into the underlying biology. Here, we used the highly sensitive, methylated DNA immunoprecipitation coupled to next generation sequencing (MeDIP) technology, to interrogate the cell-free DNA methylomes across localized and metastatic prostate cancer.","abstract":"Metastatic prostate cancer remains a major clinical challenge. Liquid biopsy is emerging as a promising tool in disease management and provides valuable opportunities to gain insights into the underlying biology. Here, we used the highly sensitive, methylated DNA immunoprecipitation coupled to next generation sequencing (MeDIP) technology, to interrogate the cell-free DNA methylomes across localized and metastatic prostate cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006193","title":"The cell free DNA methylome of primary and metastatic prostate tumors -- CRPC samples, VPC validation","description":"Metastatic prostate cancer remains a major clinical challenge. Liquid biopsy is emerging as a promising tool in disease management and provides valuable opportunities to gain insights into the underlying biology. Here, we used the highly sensitive, methylated DNA immunoprecipitation coupled to next generation sequencing (MeDIP) technology, to interrogate the cell-free DNA methylomes across localized and metastatic prostate cancer.","abstract":"Metastatic prostate cancer remains a major clinical challenge. Liquid biopsy is emerging as a promising tool in disease management and provides valuable opportunities to gain insights into the underlying biology. Here, we used the highly sensitive, methylated DNA immunoprecipitation coupled to next generation sequencing (MeDIP) technology, to interrogate the cell-free DNA methylomes across localized and metastatic prostate cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006194","title":"The cell free DNA methylome of primary and metastatic prostate tumors -- CRPC samples, WCDT","description":"Metastatic prostate cancer remains a major clinical challenge. Liquid biopsy is emerging as a promising tool in disease management and provides valuable opportunities to gain insights into the underlying biology. Here, we used the highly sensitive, methylated DNA immunoprecipitation coupled to next generation sequencing (MeDIP) technology, to interrogate the cell-free DNA methylomes across localized and metastatic prostate cancer.","abstract":"Metastatic prostate cancer remains a major clinical challenge. Liquid biopsy is emerging as a promising tool in disease management and provides valuable opportunities to gain insights into the underlying biology. Here, we used the highly sensitive, methylated DNA immunoprecipitation coupled to next generation sequencing (MeDIP) technology, to interrogate the cell-free DNA methylomes across localized and metastatic prostate cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006195","title":"RNA sequencing of AD, MCI and control OM cells","description":"Total RNA sequencing of cultured OM cells derived from patients with Alzheimer's disease (AD), individuals with mild cognitive impairment (MCI) and cognitively healthy controls.","abstract":"Total RNA sequencing of cultured OM cells derived from patients with Alzheimer's disease (AD), individuals with mild cognitive impairment (MCI) and cognitively healthy controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-07T10:46:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006196","title":"Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy","description":"We studied a group of melanoma patients treated with neoadjuvant BRAF/MEK-targeted therapy (NCT02231775, n=51), and observed significantly higher rates of major pathologic response (MPR= &lt;10% viable tumor at resection) and improved recurrence-free survival (RFS) in females versus males (MPR-66% versus 14%, p=0.001; RFS-64% versus 32% at 2 years, p=0.021). Findings were validated in a several additional cohorts 2-4 patients with unresectable metastatic melanoma treated with BRAF and/or MEK-targeted therapy (n=664 patients in total), demonstrating improved progression-free survival (PFS) and overall survival (OS) in females versus males in several of these studies. Studies in pre-clinical models demonstrated significantly impaired anti-tumor activity in male versus female BRAF/MEK-treated mice (p=0.006), with significantly higher expression of androgen receptor (AR) in tumors of male and female BRAF/MEK-treated mice versus control (p=0.0006 and 0.0025). Pharmacologic inhibition of AR signaling improved responses to BRAF/MEK-targeted therapy in male and female mice (p=0.018 and p=0.003), whereas induction of AR signaling (via testosterone administration) was associated with significantly impaired response to BRAF/MEK-targeted therapy in males and females (p=0.021 and p&lt;0.0001).","abstract":"We studied a group of melanoma patients treated with neoadjuvant BRAF/MEK-targeted therapy (NCT02231775, n=51), and observed significantly higher rates of major pathologic response (MPR= &lt;10% viable tumor at resection) and improved recurrence-free survival (RFS) in females versus males (MPR-66% versus 14%, p=0.001; RFS-64% versus 32% at 2 years, p=0.021). Findings were validated in a several additional cohorts 2-4 patients with unresectable metastatic melanoma treated with BRAF and/or MEK-targeted therapy (n=664 patients in total), demonstrating improved progression-free survival (PFS) and overall survival (OS) in females versus males in several of these studies. Studies in pre-clinical models demonstrated significantly impaired anti-tumor activity in male versus female BRAF/MEK-treated mice (p=0.006), with significantly higher expression of androgen receptor (AR) in tumors of male and female BRAF/MEK-treated mice versus control (p=0.0006 and 0.0025). Pharmacologic inhibition of AR signaling improved responses to BRAF/MEK-targeted therapy in male and female mice (p=0.018 and p=0.003), whereas induction of AR signaling (via testosterone administration) was associated with significantly impaired response to BRAF/MEK-targeted therapy in males and females (p=0.021 and p&lt;0.0001).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-07T20:15:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006197","title":"Bone_marrow_failure_project","description":"This project aims to investigate the clonal evolution of acute leukaemia, through the analysis of sequential samples from initially one individual (may in the future be expanded to include more). The individual in the study has a congenital neutropenia syndrome and has more recently developed acute myeloid leukemia. Sequential blood and bone marrow samples from this individual are available,\nincluding to the time of leukemia development. These samples will initially be sent to York (under the ethics of David Kent) and used to grow single-cell derived stem and progenitor colonies. Extracted DNA from the colonies will then be sent to the Sanger for sequencing.\nWhole genome sequencing data from the colonies will allow investigation of haematopoietic clonal changes preceding and and contributing to the leukaemia development. We will also perform targeted sequencing on bulk cell populations, including monocytes, T cells and B cells.","abstract":"This project aims to investigate the clonal evolution of acute leukaemia, through the analysis of sequential samples from initially one individual (may in the future be expanded to include more). The individual in the study has a congenital neutropenia syndrome and has more recently developed acute myeloid leukemia. Sequential blood and bone marrow samples from this individual are available,\nincluding to the time of leukemia development. These samples will initially be sent to York (under the ethics of David Kent) and used to grow single-cell derived stem and progenitor colonies. Extracted DNA from the colonies will then be sent to the Sanger for sequencing.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006198","title":"Heat selection enables highly scalable methylome profiling in cell-free DNA for noninvasive monitoring of cancer patients","description":"Genome-wide analysis of cell-free DNA (cfDNA) methylation profile has been recognized as a promising approach for sensitive and specific detection of many cancers. However, scaling such genome-wide assays for clinical translation is impractical due to the high cost of whole genome bisulfite sequencing. We have shown that the small fraction of GC-rich genome is highly enriched in CpG sites and disproportionately harbors the majority of cancer-specific methylation signature. Here, we report on the simple but effective Heat enrichment of CpG-rich regions for Bisulfite Sequencing (Heatrich-BS) platform that allows for focused methylation profiling in these highly informative regions. Our novel method and bioinformatics algorithm enable accurate tumor burden estimation with high sensitivity and quantitative tracking of colorectal cancer patient’s response to treatment, at much reduced sequencing cost suitable for frequent monitoring. We also show, for the first time, tumor epigenetic subtyping from cfDNA using Heatrich-BS, which could enable patient stratification from non-invasive liquid biopsy. As such, Heatrich-BS holds great potential for highly scalable screening and regular monitoring of cancer using liquid biopsy.","abstract":"Genome-wide analysis of cell-free DNA (cfDNA) methylation profile has been recognized as a promising approach for sensitive and specific detection of many cancers. However, scaling such genome-wide assays for clinical translation is impractical due to the high cost of whole genome bisulfite sequencing. We have shown that the small fraction of GC-rich genome is highly enriched in CpG sites and disproportionately harbors the majority of cancer-specific methylation signature. Here, we report on the simple but effective Heat enrichment of CpG-rich regions for Bisulfite Sequencing (Heatrich-BS) platform that allows for focused methylation profiling in these highly informative regions. Our novel method and bioinformatics algorithm enable accurate tumor burden estimation with high sensitivity and quantitative tracking of colorectal cancer patient’s response to treatment, at much reduced sequencing cost suitable for frequent monitoring. We also show, for the first time, tumor epigenetic subtyping from cfDNA using Heatrich-BS, which could enable patient stratification from non-invasive liquid biopsy. As such, Heatrich-BS holds great potential for highly scalable screening and regular monitoring of cancer using liquid biopsy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-11T11:08:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006199","title":"DNAme_heritability_in_solid_tissues","description":"We will attempt to overlay DNAme and RNA sequencing data onto the phylogenetic trees built using somatic mutation information. This will allow us to investigate whether there are any downstream transcriptional consequences of driver mutations. There is a growing interest in understanding whether the  somatic mutation driven clonal expansions seen in ageing morphologically normal tissues have any phenotypic consequences. this study will be conducted in a range of solid tissues (e.g. endometrium, ageing prostate)\n\n\nSecondly, it will facilitate the estimation of heritability of methylation and transcriptional states. On one hand, this will help answer a very fundamental question pertaining to what a “cell state” is. Notably, a recent paper reports that clonally heritable gene expression changes lead to significant transcriptional diversity within cells labelled as being of the same “type” (CD8memory) based on cell surface markers 9. Of particular importance to the field of ageing is estimating the heritability of DNA methylation, which has emerged as a powerful indicator of biological and chronological ageing in recent years10. There is extensive evidence suggesting that different methylation loci show different heritability and that some are more influenced by extrinsic factors whereas others seem to be under internal, developmental control11. Our study will be the first to offer a quantitative estimation of this by using the somatic mutation phylogenetic tree as a reference.","abstract":"Multi-omics study of somatic evolution in solid tissues","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006200","title":"Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer","description":"Chromosomal instability is a major challenge to patient stratification and targeted drug development for high-grade serous ovarian carcinoma (HGSOC). Here we show that somatic copy number alterations (SCNAs) in frequently amplified HGSOC cancer genes significantly correlate with gene expression and methylation status. We identified five prevalent clonal driver SCNAs (chromosomal amplifications encompassing MYC, PIK3CA, CCNE1, KRAS and TERT) from multi-regional HGSOC data and reasoned that their strong selection should prioritise them as key biomarkers for targeted therapies. We used primary HGSOC spheroid models to test interactions between in vitro targeted therapy and SCNAs. MYC chromosomal copy number was associated with in-vitro and clinical response to paclitaxel and in-vitro response to mTORC1/2 inhibition. Activation of the mTOR survival pathway in the context of MYC-amplified HGSOC was statistically associated with increased prevalence of SCNAs in genes from the PI3K pathway. Co-occurrence of amplifications in MYC and genes from the PI3K pathway was independently observed in squamous lung cancer and triple negative breast cancer. These results suggest that identifying co-occurrence of clonal driver SCNA genes could be used to tailor therapeutics for precision medicine.","abstract":"Chromosomal instability is a major challenge to patient stratification and targeted drug development for high-grade serous ovarian carcinoma (HGSOC). Here we show that somatic copy number alterations (SCNAs) in frequently amplified HGSOC cancer genes significantly correlate with gene expression and methylation status. We identified five prevalent clonal driver SCNAs (chromosomal amplifications encompassing MYC, PIK3CA, CCNE1, KRAS and TERT) from multi-regional HGSOC data and reasoned that their strong selection should prioritise them as key biomarkers for targeted therapies. We used primary HGSOC spheroid models to test interactions between in vitro targeted therapy and SCNAs. MYC chromosomal copy number was associated with in-vitro and clinical response to paclitaxel and in-vitro response to mTORC1/2 inhibition. Activation of the mTOR survival pathway in the context of MYC-amplified HGSOC was statistically associated with increased prevalence of SCNAs in genes from the PI3K pathway. Co-occurrence of amplifications in MYC and genes from the PI3K pathway was independently observed in squamous lung cancer and triple negative breast cancer. These results suggest that identifying co-occurrence of clonal driver SCNA genes could be used to tailor therapeutics for precision medicine.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-11T11:55:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006201","title":"Serum proteomics of aortic diseases","description":"Aortic diseases are a rare but potentially life-threatening condition. We present a serum proteomic study for a spectrum of aortic diseases including thoracic aortic aneurysms (n = 11), chronic dissections (n = 9), acute aortic dissections (n = 11), and surgically treated dissections (n = 19) as well as healthy controls (n = 10) and patients of coronary heart disease (n = 10) to represent non-aortic cardiovascular disease. In total, we identified and quantified 425 proteins across all 70 samples. The different aortic diseases represented distinguishable proteome profiles. We identified protein clusters that positively or negatively correlate with disease severity, including increase of cytosolic tissue leakage proteins and decrease of components of the coagulation and complement system. Further, we identified a serum proteome fingerprint of acute aortic dissections, consisting, among others, of enriched inflammatory markers such as C-reactive protein and members of the S100 protein family. The study underlines the applicability of serum proteomics for the investigation of aortic diseases and highlights the possibility to establish disease-specific prognostic markers.","abstract":"Aortic diseases are a rare but potentially life-threatening condition. We present a serum proteomic study for a spectrum of aortic diseases including thoracic aortic aneurysms (n = 11), chronic dissections (n = 9), acute aortic dissections (n = 11), and surgically treated dissections (n = 19) as well as healthy controls (n = 10) and patients of coronary heart disease (n = 10) to represent non-aortic cardiovascular disease. In total, we identified and quantified 425 proteins across all 70 samples. The different aortic diseases represented distinguishable proteome profiles. We identified protein clusters that positively or negatively correlate with disease severity, including increase of cytosolic tissue leakage proteins and decrease of components of the coagulation and complement system. Further, we identified a serum proteome fingerprint of acute aortic dissections, consisting, among others, of enriched inflammatory markers such as C-reactive protein and members of the S100 protein family. The study underlines the applicability of serum proteomics for the investigation of aortic diseases and highlights the possibility to establish disease-specific prognostic markers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-11T13:40:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006202","title":"Separation, characterization, and identification of individuals from multi-person blood mixtures with single cell transcriptome sequencing and a novel bioinformatics pipeline","description":"We report a deconvolution and identification strategy of scRNA-seq datasets using mixed PMBCs data. After sequencing the data were processed with the de-goulash pipeline and analyzed with aim to identify and aquire biogeogrpahical ancestry of the involved individuals. The study includes samples of biological mixtures and in silico mixtures.","abstract":"We report a deconvolution and identification strategy of scRNA-seq datasets using mixed PMBCs data. After sequencing the data were processed with the de-goulash pipeline and analyzed with aim to identify and aquire biogeogrpahical ancestry of the involved individuals. The study includes samples of biological mixtures and in silico mixtures.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-11T14:38:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006203","title":"A method for multiplexed full-length single-molecule sequencing of the human mitochondrial genome","description":"Here we describe a method to target, multiplex and sequence full-length, native single-molecule the human mitochondrial genome utilizing the RNA-guided DNA endonuclease Cas9.","abstract":"Here we describe a method to target, multiplex and sequence full-length, native single-molecule the human mitochondrial genome utilizing the RNA-guided DNA endonuclease Cas9.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-12T08:51:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006204","title":"Molecular Classification of Hormone Sensitive and Castration Resistant prostate cancer, using non-negative matrix factorization molecular subtyping","description":"We aim to identify molecular subtypes of prostate cancer using consensus non-negative matrix factorization and correlate these with existing biomarkers to inform future immunotherapeutic strategies.","abstract":"We aim to identify molecular subtypes of prostate cancer using consensus non-negative matrix factorization and correlate these with existing biomarkers to inform future immunotherapeutic strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-13T01:02:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006205","title":"Genetic and methylation profiles distinguish benign, malignant and spitzoid melanocytic tumors","description":"Genetic and methylation profiles distinguish benign, malignant and spitzoid melanocytic tumors","abstract":"Genetic and methylation profiles distinguish benign, malignant and spitzoid melanocytic tumors","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-13T19:22:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006206","title":"ATAC Sequencing of 4 CLL patient samples","description":"ATAC Sequencing of 4 CLL patient samples investigating differences by IGHV mutation status and trisomy 12.","abstract":"ATAC Sequencing of 4 CLL patient samples investigating differences by IGHV mutation status and trisomy 12.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-14T09:03:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006207","title":"Mutational_burden_in_oesophagus_in_high_incidence_SCC_countries","description":"We wish to get an accurate picture of the mutational burden in the oesophageal epithelium in regions of the world that have a high oesophageal SCC incidence.","abstract":"We wish to get an accurate picture of the mutational burden in the oesophageal epithelium in regions of the world that have a high oesophageal SCC incidence.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006208","title":"Molecular_QTLs_of_Human_umbilical_vein_endothelial_cells__HUVECs_","description":"We aim to characterise the range of phenotypic variation in gene expression, epigenetic regulation and intermediate functional phenotypes and its underlying genetic determinants in primary Human umbilical vein endothelial cells (HUVECs) samples We will measure gene expression by RNA sequencing (RNA-seq), genome functionality by ATAC-sequencing (ATAC-seq, to determine which regions are in an open chromatin state) and by determining H3 lysine 27acetylation (H3K27ac), a marker of active transcriptional enhancers, localisation genome wide by chromatin immunoprecipitation coupled with sequencing (ChIP-seq).","abstract":"We aim to characterise the range of phenotypic variation in gene expression, epigenetic regulation and intermediate functional phenotypes and its underlying genetic determinants in primary Human umbilical vein endothelial cells (HUVECs) samples We will measure gene expression by RNA sequencing (RNA-seq), genome functionality by ATAC-sequencing (ATAC-seq, to determine which regions are in an open chromatin state) and by determining H3 lysine 27acetylation (H3K27ac), a marker of active transcriptional enhancers, localisation genome wide by chromatin immunoprecipitation coupled with sequencing (ChIP-seq).","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-14T13:21:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006209","title":"Assessment_of_mutational_signatures_in_hacats_following_8MOP_and_UVA_treatment","description":"DNA from the epidermis of patients given PUVA treatment (psoralen and UVA) appear to have a distinctive mutational signature.  We wish to confirm this signature is genuinely down to the PUVA treatment by dosing a commercial skin cell line with 8MOP and psoralen (both independently and together).","abstract":"DNA from the epidermis of patients given PUVA treatment (psoralen and UVA) appear to have a distinctive mutational signature.  We wish to confirm this signature is genuinely down to the PUVA treatment by dosing a commercial skin cell line with 8MOP and psoralen (both independently and together).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006210","title":"Salivary Gland Cancer TSO500 dataset","description":null,"abstract":"Salivary gland cancer (SGC) is a rare cancer for which systemic treatment options are limited. Therefore, it is important to characterize its genetic landscape in search for actionable aberrations. This research aimed to identify these actionable aberrations by NGS-based analysis of DNA (single and multiple nucleotide variants, copy number variants, microsatellite instability and tumor mutational burden) in a large cohort of SGC patients.\nDNA was extracted from archival tissue of 119 patients with various SGC subtypes and sequenced using a targeted NGS panel encompassing 523 cancer related genes (TruSight Oncology 500, TSO500). The 119 patients included 46 AdCC patients, 43 SDC patients, 15 MEC patients, 9 AciCC patients and 6 patients with other subtypes (1 secretory carcinoma, 1 polymorphic adenocarcinoma (PAC), 1 adenocarcinoma NOS, 1 myoepithelial carcinoma, 1 epithelial/myoepithelial carcinoma and 1 mixed PAC/myoepithelial carcinoma). Median exon coverage ranged from 80-904 (median 308) unique reads and the median percentage of exon coverage with at least 100 unique reads was median 96.6% in these 119 samples.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006211","title":"Gremlin 1 + fibroblastic niche maintains dendritic cell homeostasis in lymphoid tissues","description":"Although cross-species transcriptional analysis has been generated for DCs37, transcriptomic conservation between mouse and human FRCs at single-cell resolution has been unclear. To test whether GREM1+ FRCs might also play a role in DC homeostasis in humans, we performed scRNA-seq of CD45–PDPN+ stromal cells, as well as CD45+CD11c+ immune cells from healthy human LNs of three donors.","abstract":"Although cross-species transcriptional analysis has been generated for DCs37, transcriptomic conservation between mouse and human FRCs at single-cell resolution has been unclear. To test whether GREM1+ FRCs might also play a role in DC homeostasis in humans, we performed scRNA-seq of CD45–PDPN+ stromal cells, as well as CD45+CD11c+ immune cells from healthy human LNs of three donors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-16T19:32:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006212","title":"WXS and RNA-seq for 22 patients treated with radiation + immunotherapy","description":"Over 500 active clinical trials are investigating combination radiation (RT) and immune checkpoint blockade (ICB) as a cancer treatment; however, the majority of trials have found no positive interaction. We performed a comprehensive molecular analysis of a randomized phase I clinical trial of patients with non-small cell lung cancer (NSCLC) treated with concurrent or sequential ablative RT and ICB. Concurrent treatment was superior to sequential treatment in augmenting local and distant tumor responses and improving overall survival in a subset of patients with highly aneuploid tumors, but not in those with less aneuploid tumors. Our analysis suggested that concurrent treatment eliminated immunologically cold aneuploid tumors better than sequential treatment and improved patient outcomes. In addition, we report that RT alone decreased intratumoral cytotoxic effector T cell and adaptive immune gene expression signatures, in contrast to upregulation of key immune pathways after concurrent administration of RT and ICB. Our findings distinguish the differential genomic and transcriptomic effects of RT versus RT and ICB and challenge the prevailing paradigm that local ablative RT beneficially stimulates the immune response. We propose the use of tumor aneuploidy as a novel biomarker and therapeutic target in personalizing treatment approaches for patients with NSCLC treated with RT and ICB.","abstract":"Over 500 active clinical trials are investigating combination radiation (RT) and immune checkpoint blockade (ICB) as a cancer treatment; however, the majority of trials have found no positive interaction. We performed a comprehensive molecular analysis of a randomized phase I clinical trial of patients with non-small cell lung cancer (NSCLC) treated with concurrent or sequential ablative RT and ICB. Concurrent treatment was superior to sequential treatment in augmenting local and distant tumor responses and improving overall survival in a subset of patients with highly aneuploid tumors, but not in those with less aneuploid tumors. Our analysis suggested that concurrent treatment eliminated immunologically cold aneuploid tumors better than sequential treatment and improved patient outcomes. In addition, we report that RT alone decreased intratumoral cytotoxic effector T cell and adaptive immune gene expression signatures, in contrast to upregulation of key immune pathways after concurrent administration of RT and ICB. Our findings distinguish the differential genomic and transcriptomic effects of RT versus RT and ICB and challenge the prevailing paradigm that local ablative RT beneficially stimulates the immune response. We propose the use of tumor aneuploidy as a novel biomarker and therapeutic target in personalizing treatment approaches for patients with NSCLC treated with RT and ICB.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-17T15:53:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006213","title":"Somatic L1 retrotranspositions in normal human cells","description":"Genomic mutations accumulate in normal cells during lifetime; however, somatic mosaicism generated by mobilization of transposable elements is not well understood. Here, we explored whole-genome sequences of single-cell expanded clones to illustrate the mutational landscape produced by L1. In addition, we analyzed promoter DNA methylation status of retrotransposition-competent L1 and read-through RNA expression profiles to investigate the epigenetic regulation of L1 activity.","abstract":"Genomic mutations accumulate in normal cells during lifetime; however, somatic mosaicism generated by mobilization of transposable elements is not well understood. Here, we explored whole-genome sequences of single-cell expanded clones to illustrate the mutational landscape produced by L1. In addition, we analyzed promoter DNA methylation status of retrotransposition-competent L1 and read-through RNA expression profiles to investigate the epigenetic regulation of L1 activity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-18T15:22:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006214","title":"scRNA mCRC PDO","description":"scRNA of five mCRC organoids in basal conditions","abstract":"scRNA of five mCRC organoids in basal conditions","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-19T11:22:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006215","title":"Transcriptomic analysis of peripheral blood dendritic cells and monocytes from patients with familial chilblain lupus and hetereozygous mutations in TREX1","description":null,"abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-19T18:27:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006216","title":"Whole-Exome Sequencing in a TGCT Mexican cohort to elucidate platinum-based therapy response","description":null,"abstract":"In this study we conducted the Whole-Exome Sequencing in 39 Mexican patients widely clinical-described Testicular Germ Cell Tumors.\nWe characterized genomic profile from platinum-based chemotherapy response both CNVs and SNVs context. \nWe uncovered a novel variant with chemosensitivity biomarker potential, as well as DNA breakpoints in genes were investigated might represent an interesting research opportunity.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006217","title":"The Gut Microbiome of liver transplant recipients","description":null,"abstract":"TransplantLines is designed as a single-centre, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the cross-sectional data from liver transplant recipients is.asdf","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006218","title":"Clonal hematopoiesis is associated with adverse outcomes in patients with COVID-19","description":"Clonal hematopoiesis of indeterminate potential (CHIP) is defined as the occurrence of an expanded proportion of mature blood cells derived from a mutant hematopoietic precursor without evidence of hematological malignancies. The principle behind this is that the somatic mutation confers a fitness advantage to the cell in which it arose. Different clinical consequences are linked with this expansion. Early evidence of an association with higher mortality risk was provided. This was not related to higher rates of cancer but was associated in particular with increased cardiovascular mortality. Mechanistically, inflammatory processes are not only related to the development of clonal hematopoiesis, but in turn it is also a driver of inflammation. Besides pulmonary symptoms, COVID-19 evokes complex extra-pulmonary manifestations driving the pathophysiology. Among them, both inflammatory and cardiac-associated mechanisms have been deciphered. With the aim of assessing the impact of clonal hematopoiesis on the pathophysiology of COVID-19, hospitalized patients with severe or critical course were evaluated for the presence of CHIP driver mutations and, more importantly, the association with the clinical picture.","abstract":"Clonal hematopoiesis of indeterminate potential (CHIP) is defined as the occurrence of an expanded proportion of mature blood cells derived from a mutant hematopoietic precursor without evidence of hematological malignancies. The principle behind this is that the somatic mutation confers a fitness advantage to the cell in which it arose. Different clinical consequences are linked with this expansion. Early evidence of an association with higher mortality risk was provided. This was not related to higher rates of cancer but was associated in particular with increased cardiovascular mortality. Mechanistically, inflammatory processes are not only related to the development of clonal hematopoiesis, but in turn it is also a driver of inflammation. Besides pulmonary symptoms, COVID-19 evokes complex extra-pulmonary manifestations driving the pathophysiology. Among them, both inflammatory and cardiac-associated mechanisms have been deciphered. With the aim of assessing the impact of clonal hematopoiesis on the pathophysiology of COVID-19, hospitalized patients with severe or critical course were evaluated for the presence of CHIP driver mutations and, more importantly, the association with the clinical picture.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-25T07:46:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006219","title":"scRNAseq_of_newly_diagnosed_IBD","description":"We will perform scRNAseq of newly diagnosed IBD patient terminal ileum and blood, and patients will be longitudinally followed up\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Next QQ we will perform scRNAseq of newly diagnosed IBD patient terminal ileum and blood, and patients will be longitudinally followed up. Addenbrooke’s Endoscopy team make new diagnoses for approximately 7 patients per year, and so we would like to get a head start by collection of these rare samples now. Funds will enable us to perform 3’v3.1 scRNAseq of terminal ileum and blood (6000 cells per sample) and NovaSeq (6 samples per lane) for 10 patients or fewer patients and multiple timepoints.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-25T09:23:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006220","title":"Test study","description":null,"abstract":"This is a test study. Oh yeah.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006221","title":"test","description":null,"abstract":"tesr","study_type":"Exome Sequencing","pubmed_ids":[12345678],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006222","title":"MGP Panel: a comprehensive targeted genomics panel for molecular profiling of multiple myeloma patients","description":"We designed a comprehensive multiple myeloma (MM) targeted sequencing panel to identify common genomic abnormalities in a single assay and validated it against known standards. The panel comprised 228 genes/exons for mutations, 6 regions for translocations, and 56 regions for copy number abnormalities (CNAs). Toward panel validation, targeted sequencing was conducted on 233 patient samples and further validated using clinical fluorescence in situ hybridization (FISH) (translocations), multiplex ligation probe analysis (MLPA) (CNAs), whole genome sequencing (WGS) (CNAs, mutations, translocations) or droplet digital PCR (ddPCR) of known standards (mutations). Canonical IgH translocations were detected in 43.2% of patients by sequencing, and aligned with FISH except for one patient. CNAs determined by sequencing and MLPA for 22 regions were comparable in 103 samples and concordance between platforms was R2=0.969. VAFs for 74 mutations were compared between sequencing and ddPCR with concordance of R2=0.9849. In summary, we have developed a targeted sequencing panel that is as robust or superior to FISH and WGS. This molecular panel is cost effective, comprehensive, clinically actionable and can be routinely deployed to assist risk stratification at diagnosis or post-treatment to guide sequencing of therapies.","abstract":"We designed a comprehensive multiple myeloma (MM) targeted sequencing panel to identify common genomic abnormalities in a single assay and validated it against known standards. The panel comprised 228 genes/exons for mutations, 6 regions for translocations, and 56 regions for copy number abnormalities (CNAs). Toward panel validation, targeted sequencing was conducted on 233 patient samples and further validated using clinical fluorescence in situ hybridization (FISH) (translocations), multiplex ligation probe analysis (MLPA) (CNAs), whole genome sequencing (WGS) (CNAs, mutations, translocations) or droplet digital PCR (ddPCR) of known standards (mutations). Canonical IgH translocations were detected in 43.2% of patients by sequencing, and aligned with FISH except for one patient. CNAs determined by sequencing and MLPA for 22 regions were comparable in 103 samples and concordance between platforms was R2=0.969. VAFs for 74 mutations were compared between sequencing and ddPCR with concordance of R2=0.9849. In summary, we have developed a targeted sequencing panel that is as robust or superior to FISH and WGS. This molecular panel is cost effective, comprehensive, clinically actionable and can be routinely deployed to assist risk stratification at diagnosis or post-treatment to guide sequencing of therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-25T10:05:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006223","title":"HCA_Gut_Adult_WSSS_Spatial__Oxford","description":"Spatial Cell atlas of the human adult gut","abstract":"Human Cell Atlas for gut - Adult RNA work. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006224","title":"Engineered_cartilage__deriving_design_principles_from_human_developmental_pathways","description":"Engineered cartilage: deriving design principles from human developmental pathways","abstract":"Engineered cartilage: deriving design principles from human developmental pathways","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-25T11:39:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006225","title":"The Gut Microbiome of renal transplant recipient Longitudinal","description":null,"abstract":"TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the longitudinal data from renal and liver transplant recipients is.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006226","title":"The Gut Microbiome of liver transplant recipients Cross sectional","description":null,"abstract":"TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the cross-sectional data from liver transplant recipients is.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006227","title":"The Gut Microbiome of renal transplant recipients Cross sectional","description":null,"abstract":"TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the cross-sectional data from renal transplant recipients is.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006228","title":"Serum Proteome Profiling Identifies Early Markers of Therapeutic Response to Neoadjuvant Chemotherapy of Breast Cancer","description":null,"abstract":"We performed a proteomic serum profiling of patients with non-metastasized breast cancer (BC) who received neoadjuvant chemotherapy (NACT). Samples were collected at three timepoints during NACT. Furthermore, we compared serum samples of BC patients pre-NACT to a control group of healthy volunteers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-25T14:13:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006229","title":"Biomarker Data from KATHERINE: A Phase III Study of Adjuvant Trastuzumab Emtansine versus Trastuzumab in Patients with Residual Invasive Disease after Neoadjuvant Therapy for HER2-Positive Breast Cancer","description":null,"abstract":"KATHERINE (NCT01772472) compared adjuvant trastuzumab emtansine (T-DM1) and trastuzumab following neoadjuvant HER2-targeted therapy and chemotherapy in patients with residual invasive breast cancer at surgery. Exploratory analyses investigated the relationship between invasive disease-free survival (IDFS) and HER2 protein expression/gene amplification, PIK3CA hotspot mutations, and gene expression of HER2, PD-L1, CD8, predefined immune signatures, and Prediction Analysis of Microarray 50 intrinsic molecular subtypes. T-DM1 improved IDFS versus trastuzumab across major biomarker subgroups. High versus low HER2 gene expression in the surgical residual tumor sample was associated with worse outcomes with trastuzumab (HR, 2.02; 95% confidence interval [CI], 1.32–3.11), but IDFS with T-DM1 was independent of HER2 expression level (HR, 1.01; 95% CI, 0.56–1.83). Low PD-L1 gene expression in the surgical residual tumor sample was associated with worse outcomes with trastuzumab (HR, 0.66; 95% CI, 0.44–1.00), but not T-DM1 (HR, 1.05; 95% CI, 0.59–1.87). PIK3CA mutations were not prognostic.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-26T00:39:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006230","title":"Extensive patient-to-patient single nuclei transcriptome heterogeneity in pheochromocytomas and paragangliomas","description":"Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors of varied genetic makeup, associated with high cardiovascular morbidity and a variable risk of malignancy. We focused on PCPG tumors with germline SDHB and RET mutations, representing distinct prognostic groups with worse or better prognoses, respectively. We applied single-nuclei RNA sequencing (snRNA-seq) on tissue samples from 11 patients.","abstract":"Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors of varied genetic makeup, associated with high cardiovascular morbidity and a variable risk of malignancy. We focused on PCPG tumors with germline SDHB and RET mutations, representing distinct prognostic groups with worse or better prognoses, respectively. We applied single-nuclei RNA sequencing (snRNA-seq) on tissue samples from 11 patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-26T11:25:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006231","title":"Targeted_NanoSeq__TIL_","description":"Exome NanoSeq in tumour-infiltrating lymphocytes from various cancer types.","abstract":"Investigating the driver landscape in tumour-infiltrating lymphocytes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006232","title":"Salivary Gland Cancer TSO500 dataset","description":"Salivary gland cancer (SGC) is a rare cancer for which systemic treatment options are limited. Therefore, it is important to characterize its genetic landscape in search for actionable aberrations. This research aimed to identify these actionable aberrations by NGS-based analysis of DNA (single and multiple nucleotide variants, copy number variants, microsatellite instability and tumor mutational burden) in a large cohort of SGC patients.\nDNA was extracted from archival tissue of 119 patients with various SGC subtypes and sequenced using a targeted NGS panel encompassing 523 cancer related genes (TruSight Oncology 500, TSO500). The 119 patients included 46 AdCC patients, 43 SDC patients, 15 MEC patients, 9 AciCC patients and 6 patients with other subtypes (1 secretory carcinoma, 1 polymorphic adenocarcinoma (PAC), 1 adenocarcinoma NOS, 1 myoepithelial carcinoma, 1 epithelial/myoepithelial carcinoma and 1 mixed PAC/myoepithelial carcinoma). Median exon coverage ranged from 80-904 (median 308) unique reads and the median percentage of exon coverage with at least 100 unique reads was median 96.6% in these 119 samples.","abstract":"Salivary gland cancer (SGC) is a rare cancer for which systemic treatment options are limited. Therefore, it is important to characterize its genetic landscape in search for actionable aberrations. This research aimed to identify these actionable aberrations by NGS-based analysis of DNA (single and multiple nucleotide variants, copy number variants, microsatellite instability and tumor mutational burden) in a large cohort of SGC patients.\nDNA was extracted from archival tissue of 119 patients with various SGC subtypes and sequenced using a targeted NGS panel encompassing 523 cancer related genes (TruSight Oncology 500, TSO500). The 119 patients included 46 AdCC patients, 43 SDC patients, 15 MEC patients, 9 AciCC patients and 6 patients with other subtypes (1 secretory carcinoma, 1 polymorphic adenocarcinoma (PAC), 1 adenocarcinoma NOS, 1 myoepithelial carcinoma, 1 epithelial/myoepithelial carcinoma and 1 mixed PAC/myoepithelial carcinoma). Median exon coverage ranged from 80-904 (median 308) unique reads and the median percentage of exon coverage with at least 100 unique reads was median 96.6% in these 119 samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-27T13:01:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006233","title":"Comprehensive epigenomic profiling reveals the extent of disease-specific chromatin states and informs drug target discovery in ankylosing spondylitis","description":"Ankylosing spondylitis (AS) is a common, highly heritable inflammatory arthritis characterised by enthesitis of the spine and sacroiliac joints. Genome-wide association studies have revealed &gt;100 genetic associations but their functional effects remain largely unresolved. Here, we present a comprehensive transcriptomic and epigenomic map of disease-relevant blood immune cell subsets from AS patients and healthy controls. We report differential disease signatures for specific genomic regions from individual -omic modalities and multi-omic integration, showing enrichment at genetically associated loci and evidence for altered monocyte function in AS. We link putative functional SNPs with cognate genes using high-resolution Capture-C at 10 loci, including PTGER4 and ETS1. We also show how disease-specific functional genomic data can be integrated with GWAS evidence to enhance therapeutic target discovery. This study combines multiple epigenetic and transcriptional analysis with GWAS to identify cell types, candidate drug target genes and transcriptional regulation of likely pathogenic relevance.","abstract":"Ankylosing spondylitis (AS) is a common, highly heritable inflammatory arthritis characterised by enthesitis of the spine and sacroiliac joints. Genome-wide association studies have revealed &gt;100 genetic associations but their functional effects remain largely unresolved. Here, we present a comprehensive transcriptomic and epigenomic map of disease-relevant blood immune cell subsets from AS patients and healthy controls. We report differential disease signatures for specific genomic regions from individual -omic modalities and multi-omic integration, showing enrichment at genetically associated loci and evidence for altered monocyte function in AS. We link putative functional SNPs with cognate genes using high-resolution Capture-C at 10 loci, including PTGER4 and ETS1. We also show how disease-specific functional genomic data can be integrated with GWAS evidence to enhance therapeutic target discovery. This study combines multiple epigenetic and transcriptional analysis with GWAS to identify cell types, candidate drug target genes and transcriptional regulation of likely pathogenic relevance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-28T12:16:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006234","title":"Hereditary_Cerebellar_Ataxias___Whole_Genome_Sequencing___2021","description":"Looking to identify mutations in order to validate that lines we have classified as from Ataxia patients contain the disease relevant mutations. This will allow us to publish on the existance of these lines which are now commercially avalable. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Looking to identify mutations in order to validate that lines we have classified as from Ataxia patients contain the disease relevant mutations. This will allow us to publish on the existance of these lines which are now commercially avalable.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-28T12:26:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006235","title":"Whole exome sequencing of PMBCL","description":"Whole exome sequencing of 8 PMBCL samples and paired normal samples and 14 unpaired PMCL samples.","abstract":"Whole exome sequencing of 8 PMBCL samples and paired normal samples and 14 unpaired PMCL samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-29T00:40:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006236","title":"glioblastoma single cell RNAseq","description":"Understanding the cellular origin and differentiation status of glioblastoma is critical to resolve the etiology of the disease. we profile 18 patient glioblastomas by single cell RNA sequencing (scRNAseq). From this, we uncovered two principal cell-of-origin relations. Each lineage displays unique directional differentiation trajectories and transcriptional cores from the naïve cell populations. Thus, glioblastoma is defined by robust cell lineage features which may provide insights into the cell origin of the diseases.","abstract":"Understanding the cellular origin and differentiation status of glioblastoma is critical to resolve the etiology of the disease. we profile 18 patient glioblastomas by single cell RNA sequencing (scRNAseq). From this, we uncovered two principal cell-of-origin relations. Each lineage displays unique directional differentiation trajectories and transcriptional cores from the naïve cell populations. Thus, glioblastoma is defined by robust cell lineage features which may provide insights into the cell origin of the diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-29T13:35:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006237","title":"A brain precursor atlas reveals the acquisition of developmental-like states in adult cerebral tumours","description":"We generated a single-cell RNA-seq atlas capturing over 100,000 cells spanning all stages of the mouse cerebral development. By examining data from over 100 cerebral tumour samples, our study reveals that, despite the phenotypic/genotypic differences between the tumour types, they are all comprised of developmental sublineages that map most closely to embryonic or juvenile stages of development.","abstract":"We generated a single-cell RNA-seq atlas capturing over 100,000 cells spanning all stages of the mouse cerebral development. By examining data from over 100 cerebral tumour samples, our study reveals that, despite the phenotypic/genotypic differences between the tumour types, they are all comprised of developmental sublineages that map most closely to embryonic or juvenile stages of development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-04-29T14:54:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006238","title":"Breast carcinomas with osteoclast-like giant cells: a comprehensive clinico-pathological and molecular portrait and evidence of RANK-L expression","description":null,"abstract":"Breast carcinomas (BC) with osteoclast-like giant cells (OGC) are rare. Despite their distinct stromal features, their molecular characteristics remain unknown. \nThe goal of this study was to report a detailed clinico-pathological and molecular characterization of breast carcinomas with osteoclast-like giant cells (OGC) diagnosed at our institution between 2000 and 2021.\nCases were further classified as invasive carcinomas of no special type with OGC (OGC-IC NST) or metaplastic carcinomas (MC) with OGC (OGC-MC). \nRNA-seq was performed on fresh-frozen tissue from seven OGC-IC NST, two OGC-MC, seven control IC NST cases without OGC (Ctl-IC NST) (selected to show IHC subtypes, grade and stage comparable to those of OGC-IC NST), and two control MC cases without OGC (Ctl-MC).","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006239","title":"Breast carcinomas with osteoclast-like giant cells: a comprehensive clinico-pathological and molecular portrait and evidence of RANK-L expression","description":null,"abstract":"Breast carcinomas (BC) with osteoclast-like giant cells (OGC) are rare. Despite their distinct stromal features, their molecular characteristics remain unknown. \nThe goal of this study was to report a detailed clinico-pathological and molecular characterization of breast carcinomas with osteoclast-like giant cells (OGC) diagnosed at our institution between 2000 and 2021.\nCases were further classified as invasive carcinomas of no special type with OGC (OGC-IC NST) or metaplastic carcinomas (MC) with OGC (OGC-MC). \nWES was performed on 7 OGC-IC NST and on one OGC-MC, as well as on matched germline DNA. Tumor DNA was extracted from fresh-frozen tumor tissue.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006240","title":"PIAMA nasal RNAseq data","description":"This study included nasal gene expression data collected from nasal brushes of adolescents in PIAMA birth cohort.","abstract":"This study included nasal gene expression data collected from nasal brushes of adolescents in PIAMA birth cohort.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-01T09:48:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006241","title":"CITE-seq for peripheral blood samples of 5 breast cancer patients","description":null,"abstract":"We have 5 breast cancer patients who received VEN therapy. We collected their peripheral blood samples before and after long-term Venetoclax treatment. We apply CITE-seq protocol to these samples. This collection contains the all CITE-seq data for patients.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-01T16:54:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006242","title":"RNA-sequencing of mechanical stress induced osteoarthritis-like damage in aged human cartilage explants treated with the anti-deiodinase iopanoic acid","description":"The current study aimed to confirm chondroprotective effects of the D2 inhibitor iopanoic acid (IOP) in an ex vivo aged human osteochondral explant model in which injurious mechanical stress is applied to inflict OA-like damage. This dataset contains RNA-seq (Illumina HiSeq X ten) of osteochondral explant cartilage from aged human patients that underwent a joint replacement surgery due to OA (N=10 donors; n=21 explants).","abstract":"The current study aimed to confirm chondroprotective effects of the D2 inhibitor iopanoic acid (IOP) in an ex vivo aged human osteochondral explant model in which injurious mechanical stress is applied to inflict OA-like damage. This dataset contains RNA-seq (Illumina HiSeq X ten) of osteochondral explant cartilage from aged human patients that underwent a joint replacement surgery due to OA (N=10 donors; n=21 explants).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-02T10:14:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006243","title":"The Gut Microbiome of renal transplant recipients – Cross-sectional","description":null,"abstract":"TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the cross-sectional data from renal transplant recipients is.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006244","title":"The Gut Microbiome of liver transplant recipients – Cross-sectional","description":null,"abstract":"TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the cross-sectional data from liver transplant recipients is.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006245","title":"The Gut Microbiome of renal transplant recipients – Longitudinal","description":null,"abstract":"TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the longitudinal data from renal and liver transplant recipients is.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006246","title":"Single-cell RNA-seq data from 3 HGSOC patient-derived organoids and corresponding tumor or ascites","description":null,"abstract":"The broad research use of organoids from high-grade serous ovarian carcinoma (HGSOC) has been hampered by low success rates of culture establishment and scarcity of fresh tumor material. Here we describe a novel method that enabled generation and long-term expansion of a HGSOC organoid biobank with efficacy markedly improved over previous reports (55% vs. 23-38%). We established organoids from cryopreserved material, demonstrating the feasibility of using frozen tissue biobanks for HGSOC organoid derivation. Organoids recapitulated patient-specific genomic landscapes and retained the phenotypic heterogeneity of original samples. Organoid drug responses correlated with clinical treatment outcomes, but only for organoids maintained in human plasma-like medium (HPLM), highlighting the importance of relevant culture conditions in organoid-based functional assays. Taken together, we introduce a resource for efficient development and use of HGSOC organoids from cryopreserved material in ovarian cancer research.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-02T12:03:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006247","title":"Genomics characterization of BRAF-V600E colorectal cancer patients treated with anti-BRAF/EGFR","description":null,"abstract":"Anti-BRAF/EGFR combinatorial therapy was recently approved by the FDA and EMA for the treatment of metastatic BRAF-V600E colorectal cancer (CRCBRAF-V600E), however the underlying genetic determinants of its anti-tumoral efficacy remain unknown. Using whole-exome sequencing data in an internal cohort of CRCBRAF-V600E treated with anti-BRAF/EGFR ± combinatorial therapies, we discovered that patients with MSS-RNF43mutated tumors achieved a higher ORR in comparison with MSI-RNF43mutated and MSS-RNF43wild-type. Multivariate analysis of an external validation cohort showed improved PFS and OS of MSS-RNF43mutated in comparison with MSS-RNF43wild-type. In vitro assessment of RNF43 mutations identified in MSS tumors showed a loss-of-function effect. Overall, our findings support a crucial role of the RNF43-dependent modulation of the WNT pathway in the antitumor activity of anti-BRAF/EGFR ± combinatorial therapies and may guide patient stratification strategies for future clinical studies.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-02T16:15:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006248","title":"Enrichment of oral-derived bacteria in inflamed colorectal tumors and distinct associations of Fusobacterium in the mesenchymal subtype","description":null,"abstract":"The association between colorectal cancer (CRC) clinical variables and Fusobacterium, but not other intra-tumoral bacteria, has been extensively studied. Here we leveraged whole-transcriptome sequencing from 807 CRC tumor samples from the AVANT phase III trial to dually characterize tumor gene expression and intra-tumoral bacteria. After stringent filtering, 74 high-confidence taxa were identified. 17 of these species, including 4 Fusobacterium spp., were classified as orally-derived and had a robust signal within right-sided, MSI-H, and BRAF mutant tumors. Across consensus molecular subtypes (CMS), integration of Fusobacterium animalis presence and tumor gene expression revealed that F. animalis had the greatest number of associations in mesenchymal CMS4 tumors, despite an overall lower prevalence than in immune CMS1 tumors. Pathway analysis within CMS4 revealed that F. animalis, but not other highly prevalent species, was uniquely associated with pathways for collagen degradation and formation as well as IL-6 and IL-1 cytokine signaling. These associations could explain in part why Fusobacterium has been previously associated with reduced survival in mesenchymal populations. Overall, this study identified oral-derived bacteria, including Fusobacterium, as broadly more prevalent in inflamed CRC tumors compared to the other subtypes, and the association of intra-tumoral bacteria on tumor gene expression is context- and species-specific.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006249","title":"Molecular characterization of a renal cell carcinoma PDX cohort","description":null,"abstract":"Patient-derived xenograft (PDX) models represent an essential tool for the preclinical evaluation of novel targeted therapies and their combinations. In this project, we molecularly characterized a comprehensive panel of RCC PDX models with well conserved molecular and pathological features over multiple passages. PDX samples were subjected to next generation sequencing (NGS). Characterization of cancer-relevant features including driver mutations or cellular processes was performed using mutational and gene expression data in order to identify potential biomarker or treatment targets in RCC. In summary, we reported a newly established and molecularly characterized panel of RCC PDX models with high relevance for translational preclinical research.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-05T11:02:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006250","title":"DNAme_heritability_in_solid_tissues__LCM_DNA_","description":"We will attempt to overlay DNAme and RNA sequencing data onto the phylogenetic trees built using somatic mutation information. This will allow us to investigate whether there are any downstream transcriptional consequences of driver mutations. There is a growing interest in understanding whether the  somatic mutation driven clonal expansions seen in ageing morphologically normal tissues have any phenotypic consequences. this study will be conducted in a range of solid tissues (e.g. endometrium, ageing prostate)\n\n\nSecondly, it will facilitate the estimation of heritability of methylation and transcriptional states. On one hand, this will help answer a very fundamental question pertaining to what a “cell state” is. Notably, a recent paper reports that clonally heritable gene expression changes lead to significant transcriptional diversity within cells labelled as being of the same “type” (CD8memory) based on cell surface markers 9. Of particular importance to the field of ageing is estimating the heritability of DNA methylation, which has emerged as a powerful indicator of biological and chronological ageing in recent years10. There is extensive evidence suggesting that different methylation loci show different heritability and that some are more influenced by extrinsic factors whereas others seem to be under internal, developmental control11. Our study will be the first to offer a quantitative estimation of this by using the somatic mutation phylogenetic tree as a reference.","abstract":"Multi-omics study of somatic evolution in solid tissues","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006251","title":"Accumulation of copy number alterations and clinical progression across advanced prostate cancer","description":"The burden of copy number alterations positively associated with radiologically-evident distant metastases at diagnosis (P=0.00006) and showed a non-linear relationship with clinical outcome on univariable and multivariable analysis, characterised by a sharp increase in the relative risk of progression (P=0.003) and death (P=0.045) for each unit increase, stabilising into more modest increases with higher burdens. This association between copy number burden and outcome was similar in each of the four metastatic states. Copy number loss occurred significantly more frequently than gain at the lowest copy number burden quartile (q=4.1X10-6). Loss of segments in chromosome 5q21-22 and gains at 8q21-24, respectively including CHD1 and cMYC, occurred more frequently in cases with higher copy number alteration (for either region: Kolmogorov–Smirnov distance, 0.5; adjusted P&lt;0.0001). Copy number alterations showed variability across tumor regions in the same prostate. This variance associated with increased risk of distant metastases (Kruskal-Wallis test P=0.037).","abstract":"The burden of copy number alterations positively associated with radiologically-evident distant metastases at diagnosis (P=0.00006) and showed a non-linear relationship with clinical outcome on univariable and multivariable analysis, characterised by a sharp increase in the relative risk of progression (P=0.003) and death (P=0.045) for each unit increase, stabilising into more modest increases with higher burdens. This association between copy number burden and outcome was similar in each of the four metastatic states. Copy number loss occurred significantly more frequently than gain at the lowest copy number burden quartile (q=4.1X10-6). Loss of segments in chromosome 5q21-22 and gains at 8q21-24, respectively including CHD1 and cMYC, occurred more frequently in cases with higher copy number alteration (for either region: Kolmogorov–Smirnov distance, 0.5; adjusted P&lt;0.0001). Copy number alterations showed variability across tumor regions in the same prostate. This variance associated with increased risk of distant metastases (Kruskal-Wallis test P=0.037).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-05T21:22:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006252","title":"The University of Hong Kong Gastric Cancer Organoids RHO Signaling Study","description":"Objective: Cell-cell (CC) and cell-matrix (CM) adhesions are essential for epithelial cell survival, yet dissociation-induced apoptosis is frequently circumvented in malignant cells. \nDesign: We explored CC and CM dependence in 58 gastric cancer (GC) organoids by withdrawing either ROCK inhibitor, matrix, or both, to evaluate their tumorigenic potential in terms of apoptosis resistance, correlation with oncogenic driver mutations and clinical behaviour. We performed mechanistic studies to determine the role of diffuse-type GC drivers: ARHGAP fusions, RHOA, and CDH1, in modulating CC (CCi) or CM (CMi) adhesion independence. \nResults: 97% of the tumour organoids were CMi, 66% were CCi and 52% were resistant to double withdrawal (CCi/CMi), while normal organoids were neither CMi nor CCi. Clinically, the CCi/CMi phenotype was associated with an infiltrative tumour edge and advanced tumour stage. Moreover, the CCi/CMi transcriptome signature was associated with poor patient survival when applied to 3 public GC datasets. CCi/CMi and CCi phenotypes were enriched in diffuse-type GC organoids, especially in those with oncogenic driver perturbation of RHO signalling via RHOA mutation or ARHGAP fusions. Inducible knockout of ARHGAP fusions in CCi/CMi tumour organoids led to re-sensitization to CC/CM dissociation-induced apoptosis, upregulation of focal adhesion and tight junction genes, partial reversion to a more normal cystic phenotype, and inhibited xenograft formation. Normal gastric organoids engineered with CDH1 or RHOA mutations became CMi or CCi, respectively. \nConclusions: The CCi/CMi phenotype has a critical role in malignant transformation and tumour progression, offering new mechanistic information on RHO-ROCK pathway inhibition that contributes to GC pathogenicity.","abstract":"Objective: Cell-cell (CC) and cell-matrix (CM) adhesions are essential for epithelial cell survival, yet dissociation-induced apoptosis is frequently circumvented in malignant cells. \nDesign: We explored CC and CM dependence in 58 gastric cancer (GC) organoids by withdrawing either ROCK inhibitor, matrix, or both, to evaluate their tumorigenic potential in terms of apoptosis resistance, correlation with oncogenic driver mutations and clinical behaviour. We performed mechanistic studies to determine the role of diffuse-type GC drivers: ARHGAP fusions, RHOA, and CDH1, in modulating CC (CCi) or CM (CMi) adhesion independence. \nResults: 97% of the tumour organoids were CMi, 66% were CCi and 52% were resistant to double withdrawal (CCi/CMi), while normal organoids were neither CMi nor CCi. Clinically, the CCi/CMi phenotype was associated with an infiltrative tumour edge and advanced tumour stage. Moreover, the CCi/CMi transcriptome signature was associated with poor patient survival when applied to 3 public GC datasets. CCi/CMi and CCi phenotypes were enriched in diffuse-type GC organoids, especially in those with oncogenic driver perturbation of RHO signalling via RHOA mutation or ARHGAP fusions. Inducible knockout of ARHGAP fusions in CCi/CMi tumour organoids led to re-sensitization to CC/CM dissociation-induced apoptosis, upregulation of focal adhesion and tight junction genes, partial reversion to a more normal cystic phenotype, and inhibited xenograft formation. Normal gastric organoids engineered with CDH1 or RHOA mutations became CMi or CCi, respectively. \nConclusions: The CCi/CMi phenotype has a critical role in malignant transformation and tumour progression, offering new mechanistic information on RHO-ROCK pathway inhibition that contributes to GC pathogenicity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-06T07:02:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006253","title":"SARS-CoV-2 impacts the transcriptome and epigenome at the maternal-fetal interface during pregnancy","description":"SARS-CoV-2 infection during pregnancy is associated with increased incidences of adverse pregnancy outcomes, including preterm birth, stillbirth, and preeclampsia. Direct placental infection is rarely observed, which suggests that pregnancy complications associated with COVID-19 are likely the consequences involving the maternal inflammatory response. The maternal-fetal interface plays a vital role in achieving a successful pregnancy and is frequently disrupted in pregnancy complications. Therefore, elucidating the molecular pathways impacted by SARS-CoV-2 infection at the maternal-fetal interface is imperative for the understanding of the pathogenesis of COVID-19-related adverse pregnancy outcomes. Here, we generated in-depth profiles, at both bulk and single-nuclei resolutions, of the transcriptomes and epigenomes of the maternal-fetal interface from COVID-19 patients and control donors. We discovered that SARS-CoV-2 infection at late pregnancy induced activation in immune cells via upregulation of interferon inducible genes. Concomitantly, angiogenesis pathway was dysregulated in endothelial cells and fibroblasts.  These changes in gene expression were accompanied by concordant alteration to the chromatin states at corresponding cis-regulatory elements. Notably, retrotransposons were dysregulated in specific elements serving as enhancers for endogenous genes. In particular, reduced activities of LTR8B elements were functionally linked to the downregulation of Pregnancy-Specific Glycoprotein (PSG) genes and other pregnancy-related genes in syncytiotrophoblasts in the COVID-19 samples. Taken together, we demonstrate the involvement of non-coding sequences in the dysregulation of immunomodulation and angiogenesis at the maternal-fetal interface of pregnancies infected with SARS-CoV-2.","abstract":"SARS-CoV-2 infection during pregnancy is associated with increased incidences of adverse pregnancy outcomes, including preterm birth, stillbirth, and preeclampsia. Direct placental infection is rarely observed, which suggests that pregnancy complications associated with COVID-19 are likely the consequences involving the maternal inflammatory response. The maternal-fetal interface plays a vital role in achieving a successful pregnancy and is frequently disrupted in pregnancy complications. Therefore, elucidating the molecular pathways impacted by SARS-CoV-2 infection at the maternal-fetal interface is imperative for the understanding of the pathogenesis of COVID-19-related adverse pregnancy outcomes. Here, we generated in-depth profiles, at both bulk and single-nuclei resolutions, of the transcriptomes and epigenomes of the maternal-fetal interface from COVID-19 patients and control donors. We discovered that SARS-CoV-2 infection at late pregnancy induced activation in immune cells via upregulation of interferon inducible genes. Concomitantly, angiogenesis pathway was dysregulated in endothelial cells and fibroblasts.  These changes in gene expression were accompanied by concordant alteration to the chromatin states at corresponding cis-regulatory elements. Notably, retrotransposons were dysregulated in specific elements serving as enhancers for endogenous genes. In particular, reduced activities of LTR8B elements were functionally linked to the downregulation of Pregnancy-Specific Glycoprotein (PSG) genes and other pregnancy-related genes in syncytiotrophoblasts in the COVID-19 samples. Taken together, we demonstrate the involvement of non-coding sequences in the dysregulation of immunomodulation and angiogenesis at the maternal-fetal interface of pregnancies infected with SARS-CoV-2.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006254","title":"Germline sequencing","description":"Detection of SNVs/indels in the germline of pediatric cancer patients with a focus on CHEK2 germline variants.","abstract":"Detection of SNVs/indels in the germline of pediatric cancer patients with a focus on CHEK2 germline variants.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-07T15:09:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006255","title":"STEMBANCC collection of well-characterised patient-derived iPS cells","description":null,"abstract":"STEMBANCC is a source of well-characterised, patient-derived iPS cells that can help researchers study diseases, develop new treatments, and test the efficacy and safety of new drugs.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006256","title":"HCA_Skin_Adult_WSSS_Spatial_Oxford_Managed_Access","description":"WSSS Deep dive of diseased human adult skin","abstract":"Spatial transcriptome analysis of diseased human adult skin","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006257","title":"The Gut Microbiome of renal transplant recipients – Cross-sectional","description":"TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the cross-sectional data from renal transplant recipients is.","abstract":"TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the cross-sectional data from renal transplant recipients is.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-09T14:24:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006258","title":"The Gut Microbiome of liver transplant recipients – Cross-sectional + Longitudinal (renal and liver)","description":"TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the cross-sectional data from liver transplant recipients and longitudinal data from renal and liver transplant recipients.","abstract":"TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the cross-sectional data from liver transplant recipients and longitudinal data from renal and liver transplant recipients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-09T14:25:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006259","title":"The Gut Microbiome of renal transplant recipients – Longitudinal","description":"TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the longitudinal data from renal and liver transplant recipients is.","abstract":"TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the longitudinal data from renal and liver transplant recipients is.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006260","title":"Discovery of a highly widespread bacteriophage family and its associations to metabolic syndrome gut microbiomes","description":"There is significant interest in altering the course of cardiometabolic disease development via the gut microbiome. Nevertheless, the highly abundant phage members of the complex gut ecosystem -which impact gut bacteria- remain understudied. Here, we characterized gut virome changes associated with metabolic syndrome (MetS), a highly prevalent clinical condition preceding cardiometabolic disease, in 196 participants with a combination of whole genome shotgun and virus\n\nlike particle sequencing. MetS gut virome populations exhibited decreased richness and diversity, but larger inter-individual variation. These populations were enriched in phages infecting Bacteroidaceae and depleted in those infecting Ruminococcaeae. Differential abundance analysis identified eighteen viral clusters (VCs) as significantly associated with either MetS or healthy viromes. Among these are a MetS-associated Roseburia VC that is related to healthy control-associated Faecalibacterium and Oscillibacter VCs. Further analysis of these VCs revealed the Candidatus Heliusviridae, a highly widespread gut phage lineage found in 90+% of the participants. The identification of the temperate Ca. Heliusviridae provides a novel starting point to a better understanding of the effect that phages have on their bacterial hosts and the role that this plays in MetS","abstract":"There is significant interest in altering the course of cardiometabolic disease development via the gut microbiome. Nevertheless, the highly abundant phage members of the complex gut ecosystem -which impact gut bacteria- remain understudied. Here, we characterized gut virome changes associated with metabolic syndrome (MetS), a highly prevalent clinical condition preceding cardiometabolic disease, in 196 participants with a combination of whole genome shotgun and virus\n\nlike particle sequencing. MetS gut virome populations exhibited decreased richness and diversity, but larger inter-individual variation. These populations were enriched in phages infecting Bacteroidaceae and depleted in those infecting Ruminococcaeae. Differential abundance analysis identified eighteen viral clusters (VCs) as significantly associated with either MetS or healthy viromes. Among these are a MetS-associated Roseburia VC that is related to healthy control-associated Faecalibacterium and Oscillibacter VCs. Further analysis of these VCs revealed the Candidatus Heliusviridae, a highly widespread gut phage lineage found in 90+% of the participants. The identification of the temperate Ca. Heliusviridae provides a novel starting point to a better understanding of the effect that phages have on their bacterial hosts and the role that this plays in MetS","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-09T14:50:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006261","title":"Molecular determinants of outcomes in relapsed or refractory mantle cell lymphoma treated with ibrutinib or temsirolimus in the MCL3001 (RAY) trial","description":"Mantle cell lymphoma (MCL) is a rare, incurable lymphoma subtype characterized by heterogeneous outcomes. In order to better understand the clinical behavior and response to treatment, powerful predictive biomarkers are needed. Using residual archived material from patients enrolled in the MCL3001 (RAY) study, we performed a detailed analysis of gene expression and genetic sequencing. This phase III clinical trial randomized patients with relapsed or refractory MCL to treatment with either ibrutinib or temsirolimus. We confirmed the prognostic capability of the RNA expression proliferation assay MCL35 in this cohort treated with novel agents, which outperformed the simplified MCL International Prognostic Index in discriminating patients with different outcomes. Regardless of treatment arm, we demonstrated that this assay captures the risk conferred by known biological factors, such as increased MYC-expression, blastoid morphology, aberrations of TP53, and truncated CCND1 3’untranslated region. We further showed the negative impact of BIRC3 mutations/deletions on outcomes in this cohort, and identified that deletion of chromosome 8p23.3 also has a deleterious effect on survival. Restricted to patients with deletions/alterations in TP53, ibrutinib appeared to abrogate the deleterious impact on outcome. These data illustrate the potential to perform a molecular analysis of predictive biomarkers from routine patient samples that can meaningfully inform clinical practice.","abstract":"Mantle cell lymphoma (MCL) is a rare, incurable lymphoma subtype characterized by heterogeneous outcomes. In order to better understand the clinical behavior and response to treatment, powerful predictive biomarkers are needed. Using residual archived material from patients enrolled in the MCL3001 (RAY) study, we performed a detailed analysis of gene expression and genetic sequencing. This phase III clinical trial randomized patients with relapsed or refractory MCL to treatment with either ibrutinib or temsirolimus. We confirmed the prognostic capability of the RNA expression proliferation assay MCL35 in this cohort treated with novel agents, which outperformed the simplified MCL International Prognostic Index in discriminating patients with different outcomes. Regardless of treatment arm, we demonstrated that this assay captures the risk conferred by known biological factors, such as increased MYC-expression, blastoid morphology, aberrations of TP53, and truncated CCND1 3’untranslated region. We further showed the negative impact of BIRC3 mutations/deletions on outcomes in this cohort, and identified that deletion of chromosome 8p23.3 also has a deleterious effect on survival. Restricted to patients with deletions/alterations in TP53, ibrutinib appeared to abrogate the deleterious impact on outcome. These data illustrate the potential to perform a molecular analysis of predictive biomarkers from routine patient samples that can meaningfully inform clinical practice.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006262","title":"Induced pluripotent stem cell lines (iPSC lines) produced from skin and blood cells.","description":"The IMBA stem cell bank, iPSC Biobank, is a collection of induced pluripotent stem cell lines (iPSC lines) produced from skin and blood cells. The iPSC Biobank is integrated into the IMBA Stem Cell Core Facility. It stores and provides high-quality reference control panels of iPSC clones as a tool to the research community.  The resource is available to all scientists and commercial institutions. The ethical guidelines of the iPSC Biobank are always based on prevailing laws and internal regulations.","abstract":"The IMBA stem cell bank, iPSC Biobank, is a collection of induced pluripotent stem cell lines (iPSC lines) produced from skin and blood cells. The iPSC Biobank is integrated into the IMBA Stem Cell Core Facility. It stores and provides high-quality reference control panels of iPSC clones as a tool to the research community.  The resource is available to all scientists and commercial institutions. The ethical guidelines of the iPSC Biobank are always based on prevailing laws and internal regulations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-11T12:14:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006263","title":"Single-cell analysis reveals transcriptomic and epigenomic impacts on the maternal-fetal interface upon SARS-CoV-2 infection","description":"During pregnancy, the maternal-fetal interface plays vital roles in fetal development. Its disruption is frequently found in pregnancy complications. Recent works show increased incidences of adverse pregnancy outcomes in COVID-19 patients; however, the mechanism remains unclear. Here, we analyzed the molecular impacts of SARS-CoV-2 infection on the maternal-fetal interface. Generating bulk and single-nucleus transcriptomic and epigenomic profiles from COVID-19 patients and control samples, we discovered aberrant immune activation and angiogenesis patterns in distinct cells from patients. Surprisingly, retrotransposons were also dysregulated in specific cell types. Notably, reduced enhancer activities of LTR8B elements were functionally linked to the downregulation of Pregnancy-Specific Glycoprotein genes in syncytiotrophoblasts. Our findings revealed that SARS-CoV-2 infection induced significant changes to the epigenome and transcriptome at the maternal-fetal interface, which may be associated with pregnancy complications.","abstract":"During pregnancy, the maternal-fetal interface plays vital roles in fetal development. Its disruption is frequently found in pregnancy complications. Recent works show increased incidences of adverse pregnancy outcomes in COVID-19 patients; however, the mechanism remains unclear. Here, we analyzed the molecular impacts of SARS-CoV-2 infection on the maternal-fetal interface. Generating bulk and single-nucleus transcriptomic and epigenomic profiles from COVID-19 patients and control samples, we discovered aberrant immune activation and angiogenesis patterns in distinct cells from patients. Surprisingly, retrotransposons were also dysregulated in specific cell types. Notably, reduced enhancer activities of LTR8B elements were functionally linked to the downregulation of Pregnancy-Specific Glycoprotein genes in syncytiotrophoblasts. Our findings revealed that SARS-CoV-2 infection induced significant changes to the epigenome and transcriptome at the maternal-fetal interface, which may be associated with pregnancy complications.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-12T04:42:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006264","title":"Parkinson's sequencing study","description":null,"abstract":"Dummy","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006265","title":"Bulk and single-cell AML RNA-seq post ex vivo culture","description":"Bulk and single-cell RNA-seq performed on primary AML blasts cultured ex vivo for 3 days in standard or niche-like conditions.","abstract":"Bulk and single-cell RNA-seq performed on primary AML blasts cultured ex vivo for 3 days in standard or niche-like conditions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-12T11:33:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006266","title":"Genetic Determinants of Mannose-binding Lectin Activity Predispose to Thromboembolic Complications in Critical COVID-19","description":null,"abstract":"A recent study demonstrated that the complement recognition protein Mannose-binding lectin (MBL) can bind to glycosylated SARS-CoV-2 spike protein. Binding activated complement in a spike-dependent manner and inhibited SARS-CoV-2 in in vitro models. Furthermore, genetic variants near or in the MBL2 gene that encodes MBL in humans were suggested to be associated with COVID-19 requiring hospitalization.\nHere, we carried out genetic and biochemical analyses of MBL activity in plasma in a multi-center cohort of critically ill COVID-19 patients, and interrogated the publicly available summary statistics from the COVID-19 Human Genetics Initiative (COVID-19 HGI). We find no evidence that genetic variants that determine activity of the MBL pathway are associated with hospitalization or intensive care admission due to SARS-CoV-2 infection. Instead, we demonstrate that MBL2 haplotypes determine risk for thrombotic complications in critically ill COVID-19 patients. Specifically, genetically determined MBL activity confers risk for pulmonary embolism in a U-shaped manner, where haplotypes associated with intermediate MBL activity are protective. Our results demonstrate a complement-dependent mechanism for COVID-19 associated thrombosis and provide an example of how genetic variation in the innate immune system modulates thrombosis risk.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-12T15:12:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006267","title":"Transcriptome analysis of samples derived from GBM tumors, and relevant cell lines established and maintained at 5% or 20% oxygen.","description":"The goal of the study was to compare the transcriptome of patient-derived serum-free GBM cell lines to that of parental GBM tumors. For each patient, three samples were analyzed: GBM tumor, cell line growing at 5% oxygen, and cell line growing at 20% oxygen. Analysis demonstrated the enrichement in cell cycle and DNA repair gene expression in cell lines when compared to parental tumor sample. Moreover, cells cultured at 5% oxygen maintained hypoxia, carbon metabolism and tumor progression transcriptional pattern characteristic for GBM.","abstract":"The goal of the study was to compare the transcriptome of patient-derived serum-free GBM cell lines to that of parental GBM tumors. For each patient, three samples were analyzed: GBM tumor, cell line growing at 5% oxygen, and cell line growing at 20% oxygen. Analysis demonstrated the enrichement in cell cycle and DNA repair gene expression in cell lines when compared to parental tumor sample. Moreover, cells cultured at 5% oxygen maintained hypoxia, carbon metabolism and tumor progression transcriptional pattern characteristic for GBM.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-12T19:09:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006268","title":"ATM germline variants in a young adult with chronic lymphocytic leukemia:  8 years of genomic evolution","description":null,"abstract":"Whole-genome sequencing (WGS) and single-cell DNA sequencing (scDNA-seq) data of longitudinal samples covering 8 years of CLL evolution. The studied CLL was diagnosed in a young adult carrying three ATM germline variants.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-13T09:26:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006269","title":"Pathobionts in the tumour microbiota predict survival following resection for colorectal cancer","description":null,"abstract":"The gut microbiota is implicated in the pathogenesis of colorectal cancer (CRC). We aimed to map the CRC mucosal microbiota and metabolome and define the influence of the tumoral microbiota on oncological outcomes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006270","title":"SLE_Map_Main_Study__Single_Cell_Profiling_of_SLE","description":"This project aims to build a sc-eQTL map from PBMCs from 300 SLE patients and 200 healthy volunteers, stimulated with three types of stimuli and profiled at two time points. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Systemic Lupus Erythematosus (SLE) is an debilitating autoimmune condition and the development of novel therapies for SLE has been challenging. The aim of this study is to use sc-RNA-Seq to understand the functional effect of key genetic variants that have been associated with the disease. We will use  transcriptome profiling to generate a single cell eQTL map of gene expression regulation in PBMCs from individuals with SLE.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006271","title":"Monozygotic_twins_with_hereditary_spherocytosis_and_MPNHereditary_spherocytosis_in_twins","description":"Monozygotic twins with hereditary spherocytosis and MPN","abstract":"Monozygotic twins with hereditary spherocytosis and MPN","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006272","title":"Precise reconstruction of the tumor microenvironment using bulk RNA-seq and a unique machine learning-based algorithm trained on artificial transcriptomes","description":null,"abstract":"Cellular deconvolution algorithms virtually reconstruct tissue composition by analyzing the gene expression of complex tissues. Here, we present the decision tree machine learning algorithm, Kassandra, trained on a broad collection of &gt; 9,400 tissue and blood sorted cell RNA profiles to accurately reconstruct the tumor microenvironment (TME). Bioinformatic correction for technical and biological variability, aberrant cancer cell expression inclusion, and the accurate quantification and normalization of transcript expression increased the stability and robustness of Kassandra. Performance was validated on over 4,000 H&amp;E tissue slides and more than 1,000 normal and tumor tissues by comparison with cytometric, immunohistochemical or single-cell RNA-seq measurements. Kassandra accurately deconvolved stromal and immune elements of blood and tumors, revealing the role of the TME in tumor pathogenesis. Digital TME reconstruction revealed that the presence of PD1-positive CD8+ T cells strongly correlated with immunotherapy response and increased the predictive potential of established biomarkers, indicating that Kassandra could potentially be utilized in future clinical applications.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-14T14:48:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006273","title":"RFX6-mediated dysregulation defines human β cell dysfunction in early type 2 diabetes","description":null,"abstract":"A hallmark of type 2 diabetes (T2D), a major cause of world-wide morbidity and mortality, is dysfunction of insulin-producing pancreatic islet β cells. T2D genome-wide association studies (GWAS) have identified hundreds of signals, mostly in the non-coding genome and overlapping β cell regulatory elements, but translating these into biological mechanisms has been challenging. To identify early disease-driving events, we performed single cell spatial proteomics, sorted cell transcriptomics, and assessed islet physiology on pancreatic tissue from short-duration T2D and control donors. Here, through integrative analyses of these diverse modalities, we show that multiple gene regulatory modules are associated with early-stage T2D β cell-intrinsic defects. One notable example is the transcription factor RFX6, which we show is a highly connected β cell hub gene that is reduced in T2D and governs a gene regulatory network associated with insulin secretion defects and T2D GWAS variants. We validated the critical role of RFX6 in β cells through direct perturbation in primary human islets followed by physiological and single nucleus multiome profiling, which showed reduced dynamic insulin secretion and large-scale changes in the β cell transcriptome and chromatin accessibility landscape. Understanding the molecular mechanisms of complex, systemic diseases necessitates integration of signals from multiple molecules, cells, organs, and individuals and thus we anticipate this approach will be a useful template to identify and validate key regulatory networks and master hub genes for other diseases or traits with GWAS data.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-14T18:35:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006274","title":"Whole Exome Sequencing of Schizophrenia cases and controls performed at the Broad Institute on a cohort from Bristol, UK","description":null,"abstract":"The Schizophrenia Exome Sequencing Meta-analysis (SCHEMA) consortium is a large multi-site collaboration dedicated to aggregating, generating, and analyzing high-throughput sequencing data of schizophrenia patients to improve our understanding of disease architecture and advance gene discovery.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-09-09T16:01:02.499789+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006275","title":"Characterization of alternative promoter usage in advanced prostate cancer","description":null,"abstract":"In this study, we use deep whole genome transcriptome sequencing to show promoter activity changes during progression from normal prostate cells to advanced prostate disease. We show how androgen signaling and somatic alterations such as loss of the tumor suppressor RB1 or the activation of the ERG oncogene are linked to activity of transcription factors at noncanonical promoters. Alternative promoter usage analysis more accurately reflects changes in TF network during disease progression and in response to therapy. Lastly, we use matched whole genome methylation data to demonstrate a link between methylation and alternative promoter activity, dramatically improving the strength of association between gene expression and methylation data.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-16T23:06:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006276","title":"Germline variant analysis in childhood AML","description":"Analysis of rare germline variants in childhood AML in a large panel of cancer predisposition genes (n=216) compiled from literature review, and including genes involved in familial hematological malignancies (HM) and bone marrow failure (BMF) syndromes. The prevalence of extremely rare variants in the combined childhood AML cohort (n=72) was compared to that in the Medical Genome Reference Bank (MGRB; n=2570) comprising individuals aged at least 70 years with no history of cardiovascular disease, dementia or cancer. This showed a significant increase of rare alleles in childhood AML for 100% of subset comparisons. Next additional stringent filtering was applied to determine predicted damaging germline predisposition variants. Overall,  21% of the Australian cohort and 25% of the TARGET cohort presented germline variants predicted to be damaging predisposition variants.","abstract":"Analysis of rare germline variants in childhood AML in a large panel of cancer predisposition genes (n=216) compiled from literature review, and including genes involved in familial hematological malignancies (HM) and bone marrow failure (BMF) syndromes. The prevalence of extremely rare variants in the combined childhood AML cohort (n=72) was compared to that in the Medical Genome Reference Bank (MGRB; n=2570) comprising individuals aged at least 70 years with no history of cardiovascular disease, dementia or cancer. This showed a significant increase of rare alleles in childhood AML for 100% of subset comparisons. Next additional stringent filtering was applied to determine predicted damaging germline predisposition variants. Overall,  21% of the Australian cohort and 25% of the TARGET cohort presented germline variants predicted to be damaging predisposition variants.","study_type":"Other","pubmed_ids":[34521114],"external_links":null,"is_released":true,"released_date":"2022-05-17T05:21:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006277","title":"HCA_Brain_Foetal_WSSS_Dev_Spatial","description":"This study involves mapping the development of the fetal brainstem, in order to understand the process of brainstem nuclei formation across the first trimester.","abstract":"The fetal brainstem contains various regionally organised neuronal nuclei that project autonomic and motor efferents to a diversity of anatomical regions of the body, thus regulating visceral and peripheral functions such as cardiac physiology, lymphoid organ activity, and movement. It remains unclear how transcriptional regulatory networks control the establishment of the regional identities of these distinct nuclei, which are tied to their function. Here, we aim to profile the developing fetal human brainstem using single-cell and spatial transcriptomics technologies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006278","title":"HCA_Female_Reproductive_Adult_EU_H2020_HUTER_RNA","description":"HCA Female Reproductive Adult EU H2020 HUTER RNA","abstract":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetics and genomic analysis which will include single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. Findings may be validated using in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of the cells to generate organoids (HIOs). Data dissemination: We will submit any data generated from this project to the Human Cell Atlas data coordination platform (DCP). The DCP is hosted at EMBL-EBI, providing multiple cloud platforms to host the data and data portals that will ensure rapid open access to the scientific community and opportunities to develop novel analysis tools. The HCA governance structure will ensure that uniform metadata is collected, that quality control standards are in place and that primary analysis pipelines make the data easily available for future analysis.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006279","title":"HCA_Urogenital_Foetal_WSSS_Spatial","description":"Characterizing developmental trajectories and immune composition of the urinary tract at single-cell resolution","abstract":"Through development, the fetal bladder and kidney become populated by immune populations originating in nascent haematopoietic organs. These cells reside alongside stromal and epithelial compartments of the tissue, and engage in complex niche interactions. In this project we will use single-cell RNA sequencing, single-cell ATAC sequencing, and spatial genomics methods to develop an integrated model for the spatio-temporal pattern of cell-cell interactions and gene expression programmes determining leukocyte tissue residence and function in the urinary tract during fetal development.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006280","title":"A method for multiplexed full-length single-molecule sequencing of the human mitochondrial genome","description":null,"abstract":"Methods to reconstruct the mitochondrial DNA (mtDNA) sequence using short-read sequencing come with an inherent bias due to amplification and mapping. They can fail to determine the phase of variants, to capture multiple deletions and to cover the mitochondrial genome evenly. Long-read whole genome sequencing is prohibitively expensive for the purpose of mtDNA heteroplasmy detection and often does not represent the full mtDNA length. Here we describe a method to target, multiplex and sequence at high coverage full-length human mitochondrial genomes as native single-molecules, utilizing the RNA-guided DNA endonuclease Cas9. Combining Cas9 induced breaks, that define the mtDNA beginning and end of the sequencing reads, as barcodes, we achieve high demultiplexing specificity and delineation of the full-length of the mtDNA, regardless of the structural variant pattern. The long-read sequencing data is analysed with a pipeline where our newly developed software baldur efficiently detects single nucleotide heteroplasmy to below 1%, physically determines phase and can accurately disentangle complex deletions. Our workflow is a unique tool for studying mtDNA variation in health and disease, and will accelerate mitochondrial research.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-17T12:39:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006281","title":"COPD and neutrophils","description":"Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small airway inflammation, emphysema and severe breathing difficulties. Low-grade systemic inflammation is an established hallmark of severe disease, however, the molecular changes in peripheral immune cells remain far from understood. We combined multi-color flow cytometry with single-cell RNA sequencing and showed that blood neutrophil numbers are significantly increased in COPD and they are a heterogeneous population. A transcriptomic state that expressed interferon response genes correlated with alveolar damage and acute exacerbations. Furthermore, bronchoalveolar neutrophils expressed gene signatures corresponding to certain blood neutrophil states. Last, our data in a murine model of cigarette smoke exposure demonstrated that bone marrow neutrophil progenitors are expanded in smoke-treated animals and display signs of immune activation. Our study provides evidence that COPD systemic inflammation may derive from an activated haematopoietic precursor compartment.","abstract":"Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small airway inflammation, emphysema and severe breathing difficulties. Low-grade systemic inflammation is an established hallmark of severe disease, however, the molecular changes in peripheral immune cells remain far from understood. We combined multi-color flow cytometry with single-cell RNA sequencing and showed that blood neutrophil numbers are significantly increased in COPD and they are a heterogeneous population. A transcriptomic state that expressed interferon response genes correlated with alveolar damage and acute exacerbations. Furthermore, bronchoalveolar neutrophils expressed gene signatures corresponding to certain blood neutrophil states. Last, our data in a murine model of cigarette smoke exposure demonstrated that bone marrow neutrophil progenitors are expanded in smoke-treated animals and display signs of immune activation. Our study provides evidence that COPD systemic inflammation may derive from an activated haematopoietic precursor compartment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-17T16:28:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006282","title":"Evolutionary histories of breast cancer and related clones","description":null,"abstract":"We performed multi-sampling of cancer and clonally-related non-cancer lobules from surgically obtained specimens of breast tissues using laser-capture microdissection, followed by whole genome sequencing (WGS) to reconstruct the life history of cancer and related clones. We also established single cell derived organoids from normal mammary epithelia and evaluated the somatic mutations by WGS to estimate the mutation accumulation rate in normal cells, which enabled us to infer the timing of early driver events during cancer development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-18T02:38:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006283","title":"Altered neutrophil and granulopoiesis biology underlie a poor outcome sepsis endotype","description":null,"abstract":"The maladaptive response to infection leading to the clinical syndrome of sepsis is highly heterogeneous, confounding immunotherapy trials. Here we establish the pathophysiology of a sepsis response endotype informative for immune state, disease severity, outcome and therapy. We applied whole blood single-cell multiomics (272,993 cells, n=39 individuals) and found patients with this endotype had increased IL1R2+ immature neutrophils, confirmed using CyTOF (n=41 samples) and RNA-sequencing (n=677 individuals), and upregulated STAT3 programs with plasma cytokine profiles of emergency granulopoiesis (EG). We characterised sepsis hematopoietic stem cells (29,336 cells, n=27 samples) with multiomics, and demonstrated endotype-specific EG transcriptional skewing together with STAT3 and EG master regulator CEBPB epigenetic signatures. Our findings establish an immunohematopoietic basis for a deleterious sepsis endotype and nominate IL-6/G-CSF as potential therapeutic targets.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-18T11:18:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006284","title":"COVID-19 GWAS in Japanese","description":"The Japan COVID-19 Task Force (JCTF) was established in early 2020 as a nation-wide multicenter consortium to overcome the COVID-19 pandemic in Japan. We conducted a genome-wide association study (GWAS) involving 2,393 Japanese COVID-19 cases collected in initial pandemic waves with 3,289 controls. GWAS genotyping was performed using Infinium Asian Screening Array (Illumina, USA).","abstract":"The Japan COVID-19 Task Force (JCTF) was established in early 2020 as a nation-wide multicenter consortium to overcome the COVID-19 pandemic in Japan. We conducted a genome-wide association study (GWAS) involving 2,393 Japanese COVID-19 cases collected in initial pandemic waves with 3,289 controls. GWAS genotyping was performed using Infinium Asian Screening Array (Illumina, USA).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-19T09:28:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006285","title":"Deep whole genome sequencing identifies recurrent genomic alterations in breast cancer cell lines and patient derived xenograft models","description":"Breast cancer cell lines (BCCLs) and patient-derived xenografts (PDX) are the most frequently used models in breast cancer research. Despite their widespread usage, genome sequencing of these models is incomplete, with previous studies only focusing on targeted gene panels, whole exome or shallow whole genome sequencing. Here we describe deep whole genome sequencing (WGS) of commonly used BCCL and PDX models using the Illumina X10 platform with an average ~ 60x coverage.","abstract":"Breast cancer cell lines (BCCLs) and patient-derived xenografts (PDX) are the most frequently used models in breast cancer research. Despite their widespread usage, genome sequencing of these models is incomplete, with previous studies only focusing on targeted gene panels, whole exome or shallow whole genome sequencing. Here we describe deep whole genome sequencing (WGS) of commonly used BCCL and PDX models using the Illumina X10 platform with an average ~ 60x coverage.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-20T03:23:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006286","title":"Combination of CDK4/6 with BET-bromodomain and PI3K/mTOR inhibitors in medulloblastoma in vitro and in vivo","description":"Despite improvement in the treatment of medulloblastoma (MB) over the last years, numerous patients with MYC- and MYCN-driven tumors still fail the current therapeutic regimen.  The retinoblastoma (RB) pathway is often compromised in MB with RB remaining intact suggesting that CDK4/6 inhibition might represent a therapeutic strategy for which drug combination remains understudied.  Using tumor lines grown in stem cell conditions referred as tumorspheres as well as tumor cells freshly dissociated from the brain of mice harboring intracranial patient-derived xenografts (PDX) of Group3 (G3) and Sonic Hedgehog (SHH) MB, we conducted high throughput drug combination screens using the CDK4/6 inhibitor (CDK4/6i) ribociclib as an anchor and 87 oncology drugs approved by FDA or currently in clinical trials.  Bromodomain and extra terminal (BET) and PI3K/mTOR inhibitors potentiated ribociclib’s inhibition of proliferation in G3 and SHH MB.  A reverse combination screen using BET inhibitor JQ1 as the anchor, revealed the three FDA approved CDK4/6i as the most potentiating drugs. Those synergistic combinations were tested in vivo in mice intracranially implanted with G3 and SHH MB tumor cells. Ribociclib showed single agent activity in several in vivo MB models.  However, despite in vitro synergy, combinations of ribociclib with JQ1 and ribociclib with the PI3K/mTOR inhibitor paxalisib failed to improve the survival of MB bearing mice compared to ribociclib alone.  Our data illustrates the difficulty in translating in vitro findings to in vivo for brain tumors partly due to insufficient free brain concentration and altered signaling pathways activation in vitro compared to in vivo.","abstract":"Despite improvement in the treatment of medulloblastoma (MB) over the last years, numerous patients with MYC- and MYCN-driven tumors still fail the current therapeutic regimen.  The retinoblastoma (RB) pathway is often compromised in MB with RB remaining intact suggesting that CDK4/6 inhibition might represent a therapeutic strategy for which drug combination remains understudied.  Using tumor lines grown in stem cell conditions referred as tumorspheres as well as tumor cells freshly dissociated from the brain of mice harboring intracranial patient-derived xenografts (PDX) of Group3 (G3) and Sonic Hedgehog (SHH) MB, we conducted high throughput drug combination screens using the CDK4/6 inhibitor (CDK4/6i) ribociclib as an anchor and 87 oncology drugs approved by FDA or currently in clinical trials.  Bromodomain and extra terminal (BET) and PI3K/mTOR inhibitors potentiated ribociclib’s inhibition of proliferation in G3 and SHH MB.  A reverse combination screen using BET inhibitor JQ1 as the anchor, revealed the three FDA approved CDK4/6i as the most potentiating drugs. Those synergistic combinations were tested in vivo in mice intracranially implanted with G3 and SHH MB tumor cells. Ribociclib showed single agent activity in several in vivo MB models.  However, despite in vitro synergy, combinations of ribociclib with JQ1 and ribociclib with the PI3K/mTOR inhibitor paxalisib failed to improve the survival of MB bearing mice compared to ribociclib alone.  Our data illustrates the difficulty in translating in vitro findings to in vivo for brain tumors partly due to insufficient free brain concentration and altered signaling pathways activation in vitro compared to in vivo.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-20T21:24:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006287","title":"Study to re-use","description":null,"abstract":"Abstract","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006288","title":"Combined – whole blood and skin fibroblasts - transcriptomic analysis in Psoriatic arthritis.","description":"Whole blood RNA sequencing was performed longitudinally in 27 subjects with PsA at the beginning, one month and six months after treatment and response to therapy was defined at 6 months. As control groups 7 healthy individuals and 9 subjects with rheumatoid arthritis were recruited combined with public RNA-sequencing datasets from patients with psoriasis and systemic lupus erythematous.  Differential expression analysis and weighted gene co-expression network analysis were performed to identify gene expression signatures, while deconvolution and flow cytometry to characterize the peripheral blood immune cell profile. RNA sequencing of skin fibroblasts was performed in a subset of affected (n=3) and healthy individuals (n=3) combined with CellChat to identify the blood-skin fibroblasts interaction network.","abstract":"Whole blood RNA sequencing was performed longitudinally in 27 subjects with PsA at the beginning, one month and six months after treatment and response to therapy was defined at 6 months. As control groups 7 healthy individuals and 9 subjects with rheumatoid arthritis were recruited combined with public RNA-sequencing datasets from patients with psoriasis and systemic lupus erythematous.  Differential expression analysis and weighted gene co-expression network analysis were performed to identify gene expression signatures, while deconvolution and flow cytometry to characterize the peripheral blood immune cell profile. RNA sequencing of skin fibroblasts was performed in a subset of affected (n=3) and healthy individuals (n=3) combined with CellChat to identify the blood-skin fibroblasts interaction network.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-21T14:20:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006289","title":"An alternative splicing modulator decreases mutant HTT and improves the molecular fingerprint in Huntington’s disease patient neurons","description":"Huntington's disease (HD) is a neurodegenerative disorder caused by poly-Q expansion in the Huntingtin (HTT) protein. Here, we delineate elevated mutant HTT (mHTT) levels in patient-derived cells including fibroblasts and iPSC derived cortical neurons using a GLP approved HTT assay. HD patients’ fibroblasts and cortical neurons recapitulate aberrant alternative splicing as a molecular fingerprint of HD. Branaplam is a splicing modulator currently tested in a phase II study in HD (NCT05111249). The drug lowers total HTT (tHTT) and mHTT levels in fibroblasts, iPSC, cortical progenitors, and neurons in a dose dependent manner at an IC50 consistently below 10nm without inducing cellular toxicity. Branaplam promotes inclusion of non-annotated novel exons. Amongst, a 115bp frameshift-inducing exon in the HTT transcript in Branaplam treated cells from Ctrl and HD patients leading to a profound reduction of HTT RNA and protein levels. Importantly, Branaplam ameliorates aberrant alternative splicing in HD patients’ fibroblasts and cortical neurons. These findings highlight the applicability of splicing modulators in the treatment of CAG repeat disorders and decipher their molecular effects associated with the pharmacokinetic and -dynamic properties in patient-derived cellular models.","abstract":"Huntington's disease (HD) is a neurodegenerative disorder caused by poly-Q expansion in the Huntingtin (HTT) protein. Here, we delineate elevated mutant HTT (mHTT) levels in patient-derived cells including fibroblasts and iPSC derived cortical neurons using a GLP approved HTT assay. HD patients’ fibroblasts and cortical neurons recapitulate aberrant alternative splicing as a molecular fingerprint of HD. Branaplam is a splicing modulator currently tested in a phase II study in HD (NCT05111249). The drug lowers total HTT (tHTT) and mHTT levels in fibroblasts, iPSC, cortical progenitors, and neurons in a dose dependent manner at an IC50 consistently below 10nm without inducing cellular toxicity. Branaplam promotes inclusion of non-annotated novel exons. Amongst, a 115bp frameshift-inducing exon in the HTT transcript in Branaplam treated cells from Ctrl and HD patients leading to a profound reduction of HTT RNA and protein levels. Importantly, Branaplam ameliorates aberrant alternative splicing in HD patients’ fibroblasts and cortical neurons. These findings highlight the applicability of splicing modulators in the treatment of CAG repeat disorders and decipher their molecular effects associated with the pharmacokinetic and -dynamic properties in patient-derived cellular models.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-22T17:02:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006290","title":"Oral tongue cancer sequencing study","description":null,"abstract":"Total RNA was isolated from oral tongue cancer samples and prepared libraries were performed on RNA sequencing with HiSeq 2500 (Illumina Inc., San Diego, CA).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006291","title":"Oral tongue cancer sequencing study","description":null,"abstract":"DNA was extracted from oral tongue cancer and paired adjacent normal tissues and amplified for 16S ribosomal DNA. The extracted DNA was profiled for 16S sequencing using MiSeq (Illumina Inc., San Diego, CA).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006292","title":"Oral tongue cancer sequencing study","description":null,"abstract":"DNA was extracted from oral tongue cancer and paired adjacent normal tissues and whole exome sequencing was performed on a HiSeq 2000 (Illumina Inc., San Diego, CA).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006293","title":"Oncogenic chimeric transcription factors drive tumor-specific transcription, processing, and translation of silent genomic regions","description":"Many cancers are characterized by gene fusions encoding oncogenic chimeric transcription factors (TFs) such as EWS::FLI1 in Ewing sarcoma (EwS). Here, we find that EWS::FLI1 induces the robust expression of a specific set of novel spliced and polyadenylated transcripts within otherwise transcriptionally silent regions of the genome. These neogenes (NGs) are virtually undetectable in large collections of normal tissues or non-EwS tumors and can be silenced by CRISPR interference at regulatory EWS::FLI1-bound microsatellites. Ribosome profiling and proteomics further show that some NGs are translated into highly EwS-specific peptides. More generally, we show that hundreds of NGs can be detected in diverse cancers characterized by chimeric TFs. Altogether, this study identifies the transcription, processing, and translation of novel, specific, highly expressed multi-exonic transcripts from otherwise silent regions of the genome as a new activity of aberrant TFs in cancer.","abstract":"Many cancers are characterized by gene fusions encoding oncogenic chimeric transcription factors (TFs) such as EWS::FLI1 in Ewing sarcoma (EwS). Here, we find that EWS::FLI1 induces the robust expression of a specific set of novel spliced and polyadenylated transcripts within otherwise transcriptionally silent regions of the genome. These neogenes (NGs) are virtually undetectable in large collections of normal tissues or non-EwS tumors and can be silenced by CRISPR interference at regulatory EWS::FLI1-bound microsatellites. Ribosome profiling and proteomics further show that some NGs are translated into highly EwS-specific peptides. More generally, we show that hundreds of NGs can be detected in diverse cancers characterized by chimeric TFs. Altogether, this study identifies the transcription, processing, and translation of novel, specific, highly expressed multi-exonic transcripts from otherwise silent regions of the genome as a new activity of aberrant TFs in cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-23T15:07:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006294","title":"Whole genome sequencing of multifocal small intestinal neuroendocrine tumors","description":null,"abstract":"To better understand the molecular mechanisms underlying the growth and development of multifocal SI-NETs, we performed a comprehensive genomic characterization of 75 synchronous primary tumors, 15 metastases, and corresponding normal samples from 13 patients with multifocal ileal NETs using whole genome sequencing.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-23T19:02:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006295","title":"Whole exome and genome sequencing investigations of perinatal death","description":null,"abstract":"Perinatal death, of a fetus or newborn, is a devastating event for families. Following nationwide multicentre recruitment, we assessed ‘genomic autopsy’ as an adjunct to standard autopsy for 200 families who experienced perinatal death, and provided a definite or candidate genetic diagnosis in 105 families. From this understudied cohort, half of the (candidate) diagnoses were phenotype expansions or novel disease genes, revealing previously unknown in-utero presentations of existing developmental disorders, and genomic disorders that are likely incompatible with life. Among the definite diagnoses, 43% were recessively or dominantly inherited, posing a 25% or 50% recurrence risk for future pregnancies. Ten families used their diagnosis for preimplantation or prenatal diagnosis of 12 pregnancies, facilitating the delivery of ten healthy newborns and management of two affected pregnancies. We emphasize the clinical importance of genomic investigations of perinatal death, with short turn-around times, enabling accurate counselling and options for families to prevent recurrence.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-24T03:19:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006296","title":"A protein-based oncopanel as straight forward option in comparison to target sequencing in HNSCC","description":null,"abstract":"Head and neck squamous cell carcinoma are a heterogeneous group of cancer and have limited therapy options after primary treatment fails. Therefore, additional information about the biology of the tumor is essential.\nWe analyzed tumor samples of 31 patients with a genomic (oncomine panel, ThermoFisher, Waltham, MA, USA) and a proteomic, immmohistochemical approach (oncopanel) and compared the results of their overlapping genes.\nWe found no strong correlation between both approaches and saw a higher proportion of expression of markers in the immunohistochemical approach. \nSummarized we can conclude, that both approaches complement one another and can be applied side-by-side to identify the best treatment option for HNSCC patients.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006297","title":"Low input capture Hi-C (liCHi-C) identifies promoter-enhancer interactions at high-resolution","description":null,"abstract":"Long-range interactions between regulatory elements and promoters are key in gene transcriptional control; however, their study requires large amounts of starting material, which is not compatible with clinical scenarios nor the study of rare cell populations. Here we introduce low input capture Hi-C (liCHi-C), as a cost-effective, flexible method to map and robustly compare promoter interactomes at high resolution. As a proof of its broad applicability, we implement liCHi-C to study normal and malignant human hematopoietic hierarchy in clinical samples. We demonstrate that the dynamic promoter architecture identifies developmental trajectories and orchestrates transcriptional transitions during cell-state commitment. Moreover, liCHi-C enables the identification of new disease-relevant cell types, genes and pathways potentially deregulated by non-coding alterations at distal regulatory elements. Finally, we show that liCHi-C can be harnessed to uncover genome-wide structural variants, resolve their breakpoints and infer their pathogenic effects. Collectively, our optimized liCHi-C method expands the study of 3D chromatin organization to unique, low-abundance cell populations, and offers an opportunity to uncover novel factors and regulatory networks involved in disease pathogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006298","title":"The immunopeptidome landscape associated with T cell infiltration, inflammation   and immune-editing in lung cancer","description":"One key barrier for improving efficacy of cancer immunotherapy remains patient stratification. While patients with CD3+CD8+ T cell inflamed ‘hot’ tumors typically show better response to immune checkpoint inhibitors, it is still unknown if the repertoire of HLA bound peptides (HLAp) presented in ‘hot’ and ‘cold’ tumors is substantially different. We surveyed 61 tumor regions and adjacent non-malignant lung tissues from eight lung cancer patients and performed deep antigen discovery combining immunopeptidomics, genomics, bulk and spatial transcriptomics and explored the heterogenic expression and presentation of tumor (neo)antigens. We associated diverse immune cell populations with the immunopeptidome in CD3+CD8+ T cell excluded, infiltrated, hot and cold tumors and found evidence for lack of immune-editing and higher presentation efficiency of tumor antigens in cold and CD3+CD8+ T cell excluded tumors. This could have implications for the choice of combination therapies tailored to the patient’s mutanome and microenvironment.","abstract":"One key barrier for improving efficacy of cancer immunotherapy remains patient stratification. While patients with CD3+CD8+ T cell inflamed ‘hot’ tumors typically show better response to immune checkpoint inhibitors, it is still unknown if the repertoire of HLA bound peptides (HLAp) presented in ‘hot’ and ‘cold’ tumors is substantially different. We surveyed 61 tumor regions and adjacent non-malignant lung tissues from eight lung cancer patients and performed deep antigen discovery combining immunopeptidomics, genomics, bulk and spatial transcriptomics and explored the heterogenic expression and presentation of tumor (neo)antigens. We associated diverse immune cell populations with the immunopeptidome in CD3+CD8+ T cell excluded, infiltrated, hot and cold tumors and found evidence for lack of immune-editing and higher presentation efficiency of tumor antigens in cold and CD3+CD8+ T cell excluded tumors. This could have implications for the choice of combination therapies tailored to the patient’s mutanome and microenvironment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-24T09:35:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006299","title":"RP-1843 Arcagen - Gastrointestinal rare cancers (GI)","description":"Arcagen is an EORTC/SPECTA pan-European project that aims to recruit 1000 rare cancer patients from different tumour domains of EURACAN. This study collected samples from advanced or metastatic rare cancer from patients older than 12, and analysed them using Foundation Medicine next-generation sequencing (NGS) panels (FoundationOne CDx for FFPE samples or FoundationOne Liquid CDx for blood samples). \n\nHere we are submitting two datasets that contain NGS files from gastrointestinal rare cancers (n=119):\n- Dataset 1 (32 patients): Mesothelioma of the peritoneum (n=21) and Pseudomyxoma peritonei/mucinous adenocarcinoma of the appendix (n=11)\n- Dataset 2 (87 patients):  Intra-hepatic cholangiocarcinoma (n=47), Extra-hepatic, cholangiocarcinoma (n=16), Not specified Cholangiocarcinoma (n=9), Small bowel adenocarcinoma (n=6) and other rare GI cancer (n=9)","abstract":"Arcagen is an EORTC/SPECTA pan-European project that aims to recruit 1000 rare cancer patients from different tumour domains of EURACAN. This study collected samples from advanced or metastatic rare cancer from patients older than 12, and analysed them using Foundation Medicine next-generation sequencing (NGS) panels (FoundationOne CDx for FFPE samples or FoundationOne Liquid CDx for blood samples). \n\nHere we are submitting two datasets that contain NGS files from gastrointestinal rare cancers (n=119):\n- Dataset 1 (32 patients): Mesothelioma of the peritoneum (n=21) and Pseudomyxoma peritonei/mucinous adenocarcinoma of the appendix (n=11)\n- Dataset 2 (87 patients):  Intra-hepatic cholangiocarcinoma (n=47), Extra-hepatic, cholangiocarcinoma (n=16), Not specified Cholangiocarcinoma (n=9), Small bowel adenocarcinoma (n=6) and other rare GI cancer (n=9)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-24T14:33:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006300","title":"Human Developmental Biology Resource (HDBR) abnormal fetal samples","description":"The HDBR (www.hdbr.org) is a human embryonic and fetal tissue bank supplying registered researchers with access to these valuable research materials up to 22 weeks post-conception (PMC4640175). All of the samples collected are analysed for chromosomal abnormalities, and all samples with an abnormal phenotype are either analysed by SNP array, or exome sequenced. This dataset is generated from those abnormal samples that have been analysed by exome sequencing. To request access to this dataset, or if any researcher is interested in obtaining tissue from any of the samples HDBR collect, please email enquiries@hdbr.org.","abstract":"The HDBR (www.hdbr.org) is a human embryonic and fetal tissue bank supplying registered researchers with access to these valuable research materials up to 22 weeks post-conception (PMC4640175). All of the samples collected are analysed for chromosomal abnormalities, and all samples with an abnormal phenotype are either analysed by SNP array, or exome sequenced. This dataset is generated from those abnormal samples that have been analysed by exome sequencing. To request access to this dataset, or if any researcher is interested in obtaining tissue from any of the samples HDBR collect, please email enquiries@hdbr.org.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-24T14:48:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006301","title":"iSITE__Investigation_of_Somatic_alterations_in_Tumours_of_the_Eye_spatial","description":"iSITE: Investigation of Somatic alterations in Tumours of the Eye_spatial","abstract":"Modern DNA sequencing technologies enable researchers to identify mutations that have been acquired during the lifetime of patients (somatic mutations). Some of these somatic mutations occur in cancer genes and increase the risk of developing cancer. This study will apply such sequencing technologies to cancers of the eye (ocular melanoma) in order to identify mutations associated with these cancers. Sequencing patients at different stages of their disease will allows us to build a timeline of the order of mutations that occur at each stage. We can use this information to understand how these cancers develop, spread (metastasise) and respond to treatment. Furthermore, we will look at which of these somatic mutations are present in the blood, by collecting blood samples and sequencing fragments of DNA which have been released by tumours into the bloodstream (circulating tumour DNA, ctDNA). This will determine whether ctDNA can be used as a way of monitoring mutations present in the tumour. This study will provide much needed insight into a rare and understudied cancer type, with the long-term aim of improving the survival of patients by identifying key mutations to develop novel therapies against.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006302","title":"HCA_Yolk_Sac_Foetal_WSSS_Spatial","description":"HCA Yolk Sac Foetal WSSS Spatial","abstract":"Spatial transcriptome analysis of foetal Yolk sac. The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions. Data dissemination: We will submit any data generated from this project to the Human Cell Atlas data coordination platform (DCP). The DCP is hosted at EMBL-EBI, providing multiple cloud platforms to host the data and data portals that will ensure rapid open access to the scientific community and opportunities to develop novel analysis tools.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006303","title":"HCA_Gut_Adult_WSSS_RNA","description":"Single-cell and VDJ sequencing of adult intestinal tissues from upper and lower gastrointestinal tract.","abstract":"Abstract: This project encompasses sequencing cells from healthy adult organ donor intestinal tissues from multiple anatomical regions. We will perform single cell RNA and VDJ sequencing of intestinal cells to comprehensively survey differences along the GI tract. The tissues/samples will be also used for protocol optimization and enrichment of epithelial vs stromal populations.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006304","title":"Real_time_ssRNAseq_flow_pilot","description":"Real time ssRNAseq flow pilot","abstract":"Leukymia sample flow pilot","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-24T16:44:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006305","title":"Low input capture Hi-C (liCHi-C) identifies promoter-enhancer interactions at high-resolution.","description":null,"abstract":"Long-range interactions between regulatory elements and promoters are key in gene transcriptional control; however, their study requires large amounts of starting material, which is not compatible with clinical scenarios nor the study of rare cell populations. Here we introduce low input capture Hi-C (liCHi-C), as a cost-effective, flexible method to map and robustly compare promoter interactomes at high resolution. As a proof of its broad applicability, we implement liCHi-C to study normal and malignant human hematopoietic hierarchy in clinical samples. We demonstrate that the dynamic promoter architecture identifies developmental trajectories and orchestrates transcriptional transitions during cell-state commitment. Moreover, liCHi-C enables the identification of new disease-relevant cell types, genes and pathways potentially deregulated by non-coding alterations at distal regulatory elements. Finally, we show that liCHi-C can be harnessed to uncover genome-wide structural variants, resolve their breakpoints and infer their pathogenic effects. Collectively, our optimized liCHi-C method expands the study of 3D chromatin organization to unique, low-abundance cell populations, and offers an opportunity to uncover novel factors and regulatory networks involved in disease pathogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-24T18:52:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006306","title":"Clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancers defined by genomic analysis","description":"Ductal Carcinoma In Situ (DCIS) is the most common form of pre-invasive \nbreast cancer and despite treatment a small fraction (5-10%) of DCIS\npatients present with invasive disease many years later.  A fundamental\nbiologic question is whether the invasive disease recurring in the same\nbreast is established by  tumor cells in the initial DCIS or\nrepresents  new unrelated disease.  To address this question, we\nperformed genomic analyses on the initial pure DCIS lesion and paired\ninvasive recurrent tumors in 95 patients together with single cell DNA\nsequencing in a subset of cases.  Our data shows that in 75% the\ninvasive recurrence was clonally related to the initial DCIS,\nsuggesting that the tumor cells were not eliminated during the initial\ntreatment with surgery +/- radiotherapy. Surprisingly however, 18% were\nclonally unrelated to the DCIS, representing new independent lineages,\nand 7% of cases were ambiguous.  Our findings show that although DCIS\nis often the precursor of  invasive recurrence, a significant fraction\nof invasive recurrences are unrelated to the initial DCIS. This\nknowledge is essential for accurate risk evaluation of DCIS treatment\nde-escalation strategies and the identification of predictive\nbiomarkers.","abstract":"Ductal Carcinoma In Situ (DCIS) is the most common form of pre-invasive \nbreast cancer and despite treatment a small fraction (5-10%) of DCIS\npatients present with invasive disease many years later.  A fundamental\nbiologic question is whether the invasive disease recurring in the same\nbreast is established by  tumor cells in the initial DCIS or\nrepresents  new unrelated disease.  To address this question, we\nperformed genomic analyses on the initial pure DCIS lesion and paired\ninvasive recurrent tumors in 95 patients together with single cell DNA\nsequencing in a subset of cases.  Our data shows that in 75% the\ninvasive recurrence was clonally related to the initial DCIS,\nsuggesting that the tumor cells were not eliminated during the initial\ntreatment with surgery +/- radiotherapy. Surprisingly however, 18% were\nclonally unrelated to the DCIS, representing new independent lineages,\nand 7% of cases were ambiguous.  Our findings show that although DCIS\nis often the precursor of  invasive recurrence, a significant fraction\nof invasive recurrences are unrelated to the initial DCIS. This\nknowledge is essential for accurate risk evaluation of DCIS treatment\nde-escalation strategies and the identification of predictive\nbiomarkers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-25T08:54:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006307","title":"Interrogating_gastrointestinal_tumour_resistance_and_metastasis_with_functional_precision_oncology_at_single_cell_resolution","description":"Pilot experiment to explore the heterogeneity of the colorectal organoid samples using scRNA-seq. We are planning to generate 20,000 single cells for scRNA-seq and after accounting for sequencing capture efficiency, have around 10,000 single cells available for further downstream analysis.","abstract":"Genomic characterisation of large cancer cell line panels with high-throughput drug screens enables the discovery of drug response biomarkers, cancer precision medicine, and subsequently, improved patient outcomes. Resistance to cancer therapeutics and their combinations remains a significant hurdle in improving patient outcomes. A key driver for this is the dynamic genomic heterogeneity associated within tumours. Clearly defining cellular contexts when a tumour exhibits sensitivity to therapeutics is critical to overcome tumour resistance and prevent clinical trial failure. Single-cell RNA-sequencing (scRNA-seq) has enabled further investigation of the tumour microenvironment, cell states, and plasticity. Recent cell atlasing efforts using scRNA-seq profiling has been applied to normal and cancer tissue from the esophagus and the colon. However, in-depth single-cell analysis of perturbed cancer cells arising from these cancers are lacking. Understanding how tumours develop over time and predicting their response to therapeutics is important to enable precision medicine.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006308","title":"A Risk Score Incorporating Low Pass Whole Genome Sequencing of Cell Free DNA from Patients Receiving CD19 CAR T-Cell Therapy for Large B-Cell Lymphoma","description":null,"abstract":"Patients (pts) with relapsed or refractory large B-cell lymphomas (rrLBCL) can achieve long-term remission after CD19 chimeric antigen receptor T-cell therapy (CART), but more than half of recipients will experience treatment failure. High pretreatment tumor burden by elevated LDH, metabolic tumor volume, or circulating tumor DNA (ctDNA) levels by clonotype sequencing are associated with inferior outcomes. Low pass whole genome sequencing (lpWGS) is a highly simplified assay capable of identifying copy number alterations (CNA) from cell free DNA (cfDNA) in blood and requires less time, cost, and sample volume to perform vs. other cfDNA sequencing methods; it may be an efficient and precise proxy for tumor burden to identify pts at high risk of progression after CART. Here, we performed lpWGS on pretreatment plasma samples from pts who received CART for rrLBCL and incorporated it into a prognostic risk model.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-26T21:50:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006309","title":"HNF1A haploinsufficiency causes decreased insulin expression, dysregulation of pancreatic progenitor signature genes and affects chromatin accessibility","description":null,"abstract":"Heterozygous mutations in the transcription factor Hepatocyte Nuclear Factor 1 alpha (HNF1A) are one of the most frequent causes of Maturity Onset Diabetes of the Young (MODY), yet the mechanisms by which mutations cause diabetes are not fully understood. Defects in pancreatic islet-cell development are thought to be a key mechanism but have been challenging to study since murine models of HNF1A-MODY do not fully recapitulate the human phenotype. The generation of endocrine β-like cells from hiPSC in vitro provides a method by which a human cell-based model can be used to understand the underlying pathology of HNF1A-MODY.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-27T00:18:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006310","title":"The immunopeptidome landscape associated with T cell infiltration, inflammation and immune-editing in lung cancer","description":null,"abstract":"One key barrier for improving efficacy of cancer immunotherapy remains patient stratification. While patients with CD3+CD8+ T cell inflamed ‘hot’ tumors typically show better response to immune checkpoint inhibitors, it is still unknown if the repertoire of HLA bound peptides (HLAp) presented in ‘hot’ and ‘cold’ tumors is substantially different. We surveyed 61 tumor regions and adjacent non-malignant lung tissues from eight lung cancer patients and performed deep antigen discovery combining immunopeptidomics, genomics, bulk and spatial transcriptomics and explored the heterogeneous expression and presentation of tumor (neo)antigens. We associated diverse immune cell populations with the immunopeptidome in CD3+CD8+ T cell excluded, infiltrated, hot and cold tumors and found evidence for lack of immune-editing and higher presentation efficiency of tumor antigens in cold and CD3+CD8+ T cell excluded tumors. This could have implications for the choice of combination therapies tailored to the patient’s mutanome and microenvironment.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006311","title":"HCA_Immune_Aging_Biology_RNA","description":"This project aims to generate a human lymphoid tissue atlas over space (multiple sites) and time (over 7 decades of life) using high-resolution single cell multiomics and spatial genomics approaches. For that, scRNAseq and multiome will be performed on cells from the spleen, lymph nodes, bone marrow and blood of 15 donors. In addition, multiome will be performed in stroma cells isolated from spleen and lymph nodes. Lastly, spatial transcriptomics will be performed in spleen and lymph nodes to assess cell location and tissue organisation changes with age.","abstract":"The immune system aging is responsible for the defective ability to fight infections, the lower protection obtained upon vaccination, and the increased susceptibility to cancer and autoimmune diseases in older individuals. Several alterations of the immune system that occur with aging have been described as key to immunosenescence. It is the case of the degeneration of primary lymphoid organs, the alteration of T and B cell repertoire diversity, or the abnormal systemic levels of pro-inflammatory immune mediators observed in older individuals. Notably, little is known of how human secondary lymphoid organs change with age, even though most of the immune cells reside in primary and secondary organs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006312","title":"Multiple_myeloma_precursor_genomics","description":"Whole genome sequencing of up to 45  multiple myeloma precursor samples and matched normals pairs.","abstract":"Whole genome sequencing of up to 45  multiple myeloma precursor samples and matched normals pairs.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-27T12:13:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006313","title":"Single cell transcriptomics of hESC-derived midbrain dopaminergic neurons generated by a new human development-based protocol","description":"Recent advances in stem cell technologies provide new opportunities for regenerative medicine and Parkinson’s disease modelling. However, the precise composition and quality of human embryonic stem cell (hESC)-derived preparations at the single cell level, compared to endogenous brain standards, remains to be determined. In addition, multiple developmental pathways important for midbrain dopaminergic (mDA) neuron development remain to be implemented in hESCs. Here we use mouse developmental knowledge and human single cell RNA-sequencing (scRNA-seq) data to generate a new development-based protocol to differentiate hESCs into mDA neurons. We found that Laminin 511, dual WNT activation with CHIR99021 and WNT5A, together with FGF8b, improved different aspects of midbrain patterning. Moreover, mDA neurogenesis and differentiation were enhanced by activation of liver X receptors and inhibition of fibroblast growth factor signaling. Analysis of hESC-derived midbrain cultures by scRNA-seq revealed multiple hESC-derived clusters, which resembled those in the endogenous human ventral midbrain. Moreover, high quality mDA neurons were detected and found to progressively acquire functionality in vitro. Thus, we hereby provide a hESC differentiation protocol that recapitulates several aspects of endogenous mDA neuron development, and a strategy to determine cell composition and quality of hESC-derived preparations that can be useful for disease modeling and cell therapy.","abstract":"Recent advances in stem cell technologies provide new opportunities for regenerative medicine and Parkinson’s disease modelling. However, the precise composition and quality of human embryonic stem cell (hESC)-derived preparations at the single cell level, compared to endogenous brain standards, remains to be determined. In addition, multiple developmental pathways important for midbrain dopaminergic (mDA) neuron development remain to be implemented in hESCs. Here we use mouse developmental knowledge and human single cell RNA-sequencing (scRNA-seq) data to generate a new development-based protocol to differentiate hESCs into mDA neurons. We found that Laminin 511, dual WNT activation with CHIR99021 and WNT5A, together with FGF8b, improved different aspects of midbrain patterning. Moreover, mDA neurogenesis and differentiation were enhanced by activation of liver X receptors and inhibition of fibroblast growth factor signaling. Analysis of hESC-derived midbrain cultures by scRNA-seq revealed multiple hESC-derived clusters, which resembled those in the endogenous human ventral midbrain. Moreover, high quality mDA neurons were detected and found to progressively acquire functionality in vitro. Thus, we hereby provide a hESC differentiation protocol that recapitulates several aspects of endogenous mDA neuron development, and a strategy to determine cell composition and quality of hESC-derived preparations that can be useful for disease modeling and cell therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-27T14:40:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006314","title":"Loss of RREB1 in pancreatic beta cells reduces cellular insulin content and affects endocrine cell gene expression","description":"Genome-wide studies have uncovered multiple independent signals at the RREB1 locus associated with altered type 2 diabetes risk and related glycemic traits. However, little is known about the function of the zinc finger transcription factor RREB1 in glucose homeostasis or how changes in its expression and/or function influences diabetes risk.","abstract":"Genome-wide studies have uncovered multiple independent signals at the RREB1 locus associated with altered type 2 diabetes risk and related glycemic traits. However, little is known about the function of the zinc finger transcription factor RREB1 in glucose homeostasis or how changes in its expression and/or function influences diabetes risk.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-27T23:28:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006315","title":"Submission to re-use","description":null,"abstract":"Abstract","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006316","title":"EWSR1-TFCP2 in an adolescent represents an extremely rare and aggressive form of intraosseous spindle cell rhabdomyosarcomas","description":null,"abstract":"The WHO Classification of Tumors of Soft Tissue and Bone subdivides rhabdomyosarcomas (RMS) into alveolar, embryonal, pleomorphic, and spindle cell RMS. Advances in molecular genetic diagnostics have made it possible to identify new RMS subgroups within traditional morphological entities. One of these subgroups comprises rare tumors characterized by epithelioid and spindle cell morphology, highly aggressive clinical course with pronounced tendency to intraosseous growth, and the presence of pathognomonic recurring genetic aberrations — chimeric genes/transcripts EWSR1::TFCP2, FUS::TFCP2, or MEIS1::NCOA2. Starting from 2018, only 26 reported cases of RMS have been assigned to this subgroup. The rarity of such tumors hampers their correct diagnostics for both anatomic pathologists and molecular oncologists. Here we describe a clinical case of intraosseous spindle cell RMS expressing EWSR1::TFCP2 fusion gene, encountered for the first time in our practice, in a 16-year-old female patient presenting with mandibular lesion. The diagnostic process took considerable time and involved RNA sequencing — a high-throughput method of molecular genetic research. The tumor was extremely aggressive, showing resistance to polychemotherapy, radiation therapy, and crizotinib targeted therapy, with the fatal outcome.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006317","title":"Shallow nanopore RNA sequencing enables transcriptome profiling for precision cancer medicine (Hipo_021)","description":null,"abstract":"Transcriptome profiling is a mainstay of translational cancer research and is increasingly finding its way into precision oncology. While bulk RNA sequencing (RNA-seq) is widely available, high costs and long data return time are limiting factors for clinical applications. We investigated a portable nanopore long-read sequencing device (MinION, Oxford Nanopore Technologies) for transcriptome profiling of tumors. In particular, we investigated the impact of lower coverage than that of larger sequencing devices by comparing shallow nanopore RNA-seq data with short-read RNA-seq data generated using reversible dye terminator technology (Illumina) for ten samples representing four cancer types. Coupled with ShaNTi (Shallow Nanopore Sequencing for Transcriptomics), a newly developed data processing pipeline, a turnaround time of five days was achieved. The correlation of normalized gene-level counts between nanopore and Illumina RNA-seq was high for MinION but not for very low-throughput Flongle flow cells (r = 0.89 and r = 0.24, respectively). A cost-saving approach based on multiplexing of four samples per MinION flow cell maintained a high correlation with Illumina data (r = 0.56 – 0.86). In addition, we compared the utility of nanopore and Illumina RNA-seq data for analysis tools commonly applied in translational oncology: (i) Shallow nanopore and Illumina RNA-seq were equally useful for inferring signaling pathway activities with PROGENy. (ii) Highly expressed genes encoding kinases targeted by clinically approved small-molecule inhibitors were reliably identified by shallow nanopore RNA-seq. (iii) In tumor microenvironment composition analysis, quanTIseq performed better than CIBERSORT, likely due to higher average expression of the gene set used for deconvolution. (iv) Shallow nanopore RNA-seq was successfully applied to validate known gene fusions by breakpoint analysis. These findings suggest that shallow nanopore RNA-seq enables rapid, cost-effective, and biologically meaningful transcriptome profiling of tumors and warrants further exploration in precision cancer medicine studies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-05-30T22:55:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006318","title":"Incidence of dysplasia in AML patients","description":null,"abstract":"Clonal evolution in acute myeloid leukemia (AML) originates long before diagnosis and is a dynamic process that may affect survival. However, it remains uninvestigated during routine diagnostic workup. We hypothesized that the mutational status of bone marrow dysplastic cells and leukemic blasts, analyzed at the onset of AML using integrated multidimensional flow cytometry (MFC) immunophenotyping and sorting (FACS) with next-generation sequencing (NGS), could reconstruct leukemogenesis. Dysplastic cells were detected by MFC in 285 of 348 (82%) newly-diagnosed AML patients. Presence of dysplasia according to MFC and WHO criteria had no prognostic value in the elderly. NGS of dysplastic cells and blasts isolated at diagnosis identified three evolutionary patterns: stable (n=12/21), branching (n=4/21) and clonal evolution (n=5/21). In patients achieving complete response, integrated MFC and FACS with NGS showed persistent measurable residual disease (MRD) in phenotypically normal cell types, as well as the acquisition of genetic traits associated with treatment resistance. Furthermore, whole-exome sequencing of dysplastic and leukemic cells at diagnosis and of MRD uncovered different clonal involvement in dysplastic myelo-erythropoiesis, leukemic transformation and chemoresistance. Altogether, we showed that it is possible to reconstruct leukemogenesis in ~80% of newly-diagnosed AML patients, using techniques that are commonly available in clinical laboratories.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006319","title":"Additional sequencing of CAIRO2 samples","description":"Additional sequencing of CAIRO2 study","abstract":"Additional sequencing of CAIRO2 study","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006320","title":"Childhood Cancer Model Atlas","description":"we establish a single-site collection of 243 cell lines, including 207 paediatric cancer cell lines representing 14 distinct extracranial and brain childhood tumour types. We subjected 164 paediatric cancer cell lines to multi-omic analyses across three dimensions (DNA-sequencing, RNA-sequencing, DNA methylation) to classify them based on clinically relevant molecular subtypes.","abstract":"we establish a single-site collection of 243 cell lines, including 207 paediatric cancer cell lines representing 14 distinct extracranial and brain childhood tumour types. We subjected 164 paediatric cancer cell lines to multi-omic analyses across three dimensions (DNA-sequencing, RNA-sequencing, DNA methylation) to classify them based on clinically relevant molecular subtypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-01T03:09:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006321","title":"Fragment ends of circulating microbial DNA as signatures for infectious diseases","description":"Fragment ends of circulating microbial DNA as signatures for infectious diseases","abstract":"Fragment ends of circulating microbial DNA as signatures for infectious diseases","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-02T07:26:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006322","title":"COPD and neutrophils sc","description":"Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small airway inflammation, emphysema and severe breathing difficulties. Low-grade systemic inflammation is an established hallmark of severe disease, however, the molecular changes in peripheral immune cells remain far from understood. We combined multi-color flow cytometry with single-cell RNA sequencing and showed that blood neutrophil numbers are significantly increased in COPD and they are a heterogeneous population. A transcriptomic state that expressed interferon response genes correlated with alveolar damage and acute exacerbations. Furthermore, bronchoalveolar neutrophils expressed gene signatures corresponding to certain blood neutrophil states. Last, our data in a murine model of cigarette smoke exposure demonstrated that bone marrow neutrophil progenitors are expanded in smoke-treated animals and display signs of immune activation. Our study provides evidence that COPD systemic inflammation may derive from an activated haematopoietic precursor compartment.","abstract":"Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small airway inflammation, emphysema and severe breathing difficulties. Low-grade systemic inflammation is an established hallmark of severe disease, however, the molecular changes in peripheral immune cells remain far from understood. We combined multi-color flow cytometry with single-cell RNA sequencing and showed that blood neutrophil numbers are significantly increased in COPD and they are a heterogeneous population. A transcriptomic state that expressed interferon response genes correlated with alveolar damage and acute exacerbations. Furthermore, bronchoalveolar neutrophils expressed gene signatures corresponding to certain blood neutrophil states. Last, our data in a murine model of cigarette smoke exposure demonstrated that bone marrow neutrophil progenitors are expanded in smoke-treated animals and display signs of immune activation. Our study provides evidence that COPD systemic inflammation may derive from an activated haematopoietic precursor compartment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-03T14:48:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006323","title":"COPD and neutrophils sc rhapsody","description":"Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small airway inflammation, emphysema and severe breathing difficulties. Low-grade systemic inflammation is an established hallmark of severe disease, however, the molecular changes in peripheral immune cells remain far from understood. We combined multi-color flow cytometry with single-cell RNA sequencing and showed that blood neutrophil numbers are significantly increased in COPD and they are a heterogeneous population. A transcriptomic state that expressed interferon response genes correlated with alveolar damage and acute exacerbations. Furthermore, bronchoalveolar neutrophils expressed gene signatures corresponding to certain blood neutrophil states. Last, our data in a murine model of cigarette smoke exposure demonstrated that bone marrow neutrophil progenitors are expanded in smoke-treated animals and display signs of immune activation. Our study provides evidence that COPD systemic inflammation may derive from an activated haematopoietic precursor compartment.","abstract":"Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small airway inflammation, emphysema and severe breathing difficulties. Low-grade systemic inflammation is an established hallmark of severe disease, however, the molecular changes in peripheral immune cells remain far from understood. We combined multi-color flow cytometry with single-cell RNA sequencing and showed that blood neutrophil numbers are significantly increased in COPD and they are a heterogeneous population. A transcriptomic state that expressed interferon response genes correlated with alveolar damage and acute exacerbations. Furthermore, bronchoalveolar neutrophils expressed gene signatures corresponding to certain blood neutrophil states. Last, our data in a murine model of cigarette smoke exposure demonstrated that bone marrow neutrophil progenitors are expanded in smoke-treated animals and display signs of immune activation. Our study provides evidence that COPD systemic inflammation may derive from an activated haematopoietic precursor compartment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-05T08:23:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006324","title":"Integrative modeling of tumor genomes and epigenomes for enhanced cancer diagnosis by cell-free DNA","description":null,"abstract":"3784 Cell-free DNA WGS bam files were generated on the MGI and Illumina platform. WGS paired reads were mapped to hg19 human reference genome.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006325","title":"Integrative modeling of tumor genomes and epigenomes for enhanced cancer diagnosis by cell-free DNA","description":null,"abstract":"3784 whole genome sequencing bam files were generated from plasma cell-free DNA of healthy individuals and patients with cancer. Paired reads were mapped to hg19 human reference genome.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006326","title":"Somatic_mutation_in_edited_cholangiocyte_organoids_WGS","description":"Characterisation of mutation rates and patterns in edited human cholangiocyte organoids (WGS)","abstract":"Characterisation of mutation rates and patterns in edited human cholangiocyte organoids (WGS)","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-06T09:07:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006327","title":"Detection of early seeding of Richter transformation in chronic lymphocytic leukemia","description":"Dataset accompanying the study entitled “Detection of early seeding of Richter transformation in chronic lymphocytic leukemia” (Nadeu et al. Nature Medicine 2022), which includes the analysis of longitudinal samples of 19 chronic lymphocytic leukemia patients developing Richter transformation.","abstract":"Dataset accompanying the study entitled “Detection of early seeding of Richter transformation in chronic lymphocytic leukemia” (Nadeu et al. Nature Medicine 2022), which includes the analysis of longitudinal samples of 19 chronic lymphocytic leukemia patients developing Richter transformation.","study_type":"Other","pubmed_ids":[35953718],"external_links":null,"is_released":true,"released_date":"2022-06-06T12:38:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006328","title":"Long-read sequencing for cell-free DNA analysis (human)","description":"In this study, we compared the two long-read sequencing platforms, namely the single-molecule real-time sequencing by Pacific Biosciences and nanopore sequencing by Oxford Nanopore Technologies, for the analysis of cell-free DNA from plasma. Cell-free DNA from plasma samples of 31 pregnant women at different trimesters, 6 hepatitis B carriers, and 8 patients with hepatocellular carcinoma were sequenced with the two platforms.","abstract":"In this study, we compared the two long-read sequencing platforms, namely the single-molecule real-time sequencing by Pacific Biosciences and nanopore sequencing by Oxford Nanopore Technologies, for the analysis of cell-free DNA from plasma. Cell-free DNA from plasma samples of 31 pregnant women at different trimesters, 6 hepatitis B carriers, and 8 patients with hepatocellular carcinoma were sequenced with the two platforms.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-07T08:14:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006329","title":"Long-read sequencing for cell-free DNA analysis (mouse)","description":"In this study, we compared the two long-read sequencing platforms, namely the single-molecule real-time sequencing by Pacific Biosciences and nanopore sequencing by Oxford Nanopore Technologies, for the analysis of cell-free DNA from plasma. Artificial mixtures of sonicated human and mouse DNA at different sizes were sequenced with the two platforms.","abstract":"In this study, we compared the two long-read sequencing platforms, namely the single-molecule real-time sequencing by Pacific Biosciences and nanopore sequencing by Oxford Nanopore Technologies, for the analysis of cell-free DNA from plasma. Artificial mixtures of sonicated human and mouse DNA at different sizes were sequenced with the two platforms.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-07T08:14:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006330","title":"Spatial multi-omic map of human myocardial infarction","description":"Myocardial infarction is a leading cause of mortality worldwide 1 . While advances have been made\nin acute treatment, an incomplete understanding of remodelling processes has limited the\neffectiveness of therapies to reduce late-stage mortality 2 . Here, we generate an integrative high-\nresolution map of human cardiac remodelling after myocardial infarction using single-cell gene\nexpression, chromatin accessibility, and spatial transcriptomic profiling of multiple physiological\nzones at distinct time points in myocardium from myocardial infarction and control patients.\nMultimodal data integration allowed us to evaluate cardiac cell-type compositions at increased\nresolution, yielding insights into changes of the cardiac transcriptome and epigenome through the\nidentification of distinct tissue structures of injury, repair and remodelling. We identified and\nvalidated disease-specific cardiac cell-states of major cell-types and analysed them in their spatial\ncontext, evaluating their dependency on other cell-types. Our data elucidates molecular principles\nof human myocardial tissue organisation, recapitulating a gradual cardiomyocyte and myeloid\ncontinuum following ischemic injury. In total, our study provides an integrative molecular map of\nhuman myocardial infarction and represents an essential reference for the field and paves the way\nfor advanced mechanistic and therapeutic studies of cardiac disease.","abstract":"Myocardial infarction is a leading cause of mortality worldwide 1 . While advances have been made\nin acute treatment, an incomplete understanding of remodelling processes has limited the\neffectiveness of therapies to reduce late-stage mortality 2 . Here, we generate an integrative high-\nresolution map of human cardiac remodelling after myocardial infarction using single-cell gene\nexpression, chromatin accessibility, and spatial transcriptomic profiling of multiple physiological\nzones at distinct time points in myocardium from myocardial infarction and control patients.\nMultimodal data integration allowed us to evaluate cardiac cell-type compositions at increased\nresolution, yielding insights into changes of the cardiac transcriptome and epigenome through the\nidentification of distinct tissue structures of injury, repair and remodelling. We identified and\nvalidated disease-specific cardiac cell-states of major cell-types and analysed them in their spatial\ncontext, evaluating their dependency on other cell-types. Our data elucidates molecular principles\nof human myocardial tissue organisation, recapitulating a gradual cardiomyocyte and myeloid\ncontinuum following ischemic injury. In total, our study provides an integrative molecular map of\nhuman myocardial infarction and represents an essential reference for the field and paves the way\nfor advanced mechanistic and therapeutic studies of cardiac disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-07T09:37:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006331","title":"Intratumoural heterogeneity and immune modulation in lung adenocarcinoma of female smokers and never smokers","description":"Lung cancer is still the leading cause of cancer death worldwide despite declining smoking prevalence in industrialised countries. Although lung cancer is highly associated with smoking status, a significant proportion of lung cancer cases develop in patients who never smoked, with an observable bias towards female never smokers. A better understanding of lung cancer heterogeneity and immune system involvement during tumour evolution and progression in never smokers is therefore highly warranted. We employed single nucleus transcriptomics of surgical lung adenocarcinoma (LADC) and normal lung tissue samples from patients with or without smoking history. Immune cells as well as fibroblasts and endothelial cells respond to tobacco smoke exposure by inducing a highly inflammatory state in normal lung tissue. In the presence of LADC, we identified differentially expressed transcriptional programmes in macrophages and cancer-associated fibroblasts, providing insight into how the niche favours tumour progression. Within tumours, we distinguished eight subpopulations of neoplastic cells in female smokers and never smokers. Through pseudotemporal ordering, we inferred a trajectory towards two differentiated tumour cell states implicated in cancer progression and invasiveness. A proliferating cell population sustaining tumour growth exhibits differential immune modulating signatures in both patient groups. Our results resolve cellular heterogeneity and immune interactions in LADC, with a special emphasis on female never smokers and implications for the design of therapeutic approaches.","abstract":"Lung cancer is still the leading cause of cancer death worldwide despite declining smoking prevalence in industrialised countries. Although lung cancer is highly associated with smoking status, a significant proportion of lung cancer cases develop in patients who never smoked, with an observable bias towards female never smokers. A better understanding of lung cancer heterogeneity and immune system involvement during tumour evolution and progression in never smokers is therefore highly warranted. We employed single nucleus transcriptomics of surgical lung adenocarcinoma (LADC) and normal lung tissue samples from patients with or without smoking history. Immune cells as well as fibroblasts and endothelial cells respond to tobacco smoke exposure by inducing a highly inflammatory state in normal lung tissue. In the presence of LADC, we identified differentially expressed transcriptional programmes in macrophages and cancer-associated fibroblasts, providing insight into how the niche favours tumour progression. Within tumours, we distinguished eight subpopulations of neoplastic cells in female smokers and never smokers. Through pseudotemporal ordering, we inferred a trajectory towards two differentiated tumour cell states implicated in cancer progression and invasiveness. A proliferating cell population sustaining tumour growth exhibits differential immune modulating signatures in both patient groups. Our results resolve cellular heterogeneity and immune interactions in LADC, with a special emphasis on female never smokers and implications for the design of therapeutic approaches.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-07T15:13:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006332","title":"A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in normal tissues","description":null,"abstract":"Targeted sequencing of 153 genes obtained from clinically annotated post-mortem tissue bulk samples, derived from whole-body donors that are routinely used for educational purposes at human anatomy units. We validated this post-mortem approach using UV-exposed and unexposed epidermal skin tissues and confirm the presence of positively selected NOTCH1/2-, TP53- and FAT1-driven clones. No selection signals were detected in a set of immune genes or housekeeping genes. Additionally, we provide the first evidence for smoking-induced clonal changes in oral epithelia, likely underlying the origin of head and neck carcinogenesis.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-07T16:14:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006333","title":"Genome-wide data from medieval German Jews show that the Ashkenazi founder event pre-dated the 14th century","description":"The Ashkenazi Jewish (AJ) population, which has its recent origins largely in Eastern and Central Europe, carries dozens of Mendelian pathogenic variants likely due to medieval founder events. However, little is known about these events or the early origins of the population. We report the first DNA data from historical-era AJ, from 33 individuals whose remains were rescued during salvage excavations of the medieval Jewish cemetery of Erfurt, Germany, dated to the 14th century. The Erfurt individuals are genetically similar to modern AJ and have substantial Southern European ancestry. However, the Erfurt individuals also show variability in Eastern European-related ancestry not present in modern AJ. The genetic variability was correlated with oxygen isotope ratios in tooth enamel, implying differential exposure to water sources during childhood and thus diverse geographic origins. About a third of the Erfurt individuals carried the K1a1b1a Ashkenazi-specific mitochondrial DNA haplogroup, and we detect in the Erfurt individuals 11 pathogenic variants known to affect AJ today, including alleles in the genes BRCA1, GBA, F11, CLRN1, and G6PC. Together with high genome-wide levels of runs of homozygosity, these observations suggest that the Erfurt community descended from a population that had already experienced the major reduction in size that also affected modern AJ. Modeling identical-by-descent haplotypes shows that the Erfurt founder event was more severe than expected based on reconstructions from modern AJ, implying substructure in medieval AJ whereby different groups have experienced different founder event intensities. Our results suggest that the AJ founder event and the acquisition of the main sources of AJ ancestry pre-dated the 14th century, while highlighting late medieval genetic heterogeneity no longer present in modern AJ.","abstract":"The Ashkenazi Jewish (AJ) population, which has its recent origins largely in Eastern and Central Europe, carries dozens of Mendelian pathogenic variants likely due to medieval founder events. However, little is known about these events or the early origins of the population. We report the first DNA data from historical-era AJ, from 33 individuals whose remains were rescued during salvage excavations of the medieval Jewish cemetery of Erfurt, Germany, dated to the 14th century. The Erfurt individuals are genetically similar to modern AJ and have substantial Southern European ancestry. However, the Erfurt individuals also show variability in Eastern European-related ancestry not present in modern AJ. The genetic variability was correlated with oxygen isotope ratios in tooth enamel, implying differential exposure to water sources during childhood and thus diverse geographic origins. About a third of the Erfurt individuals carried the K1a1b1a Ashkenazi-specific mitochondrial DNA haplogroup, and we detect in the Erfurt individuals 11 pathogenic variants known to affect AJ today, including alleles in the genes BRCA1, GBA, F11, CLRN1, and G6PC. Together with high genome-wide levels of runs of homozygosity, these observations suggest that the Erfurt community descended from a population that had already experienced the major reduction in size that also affected modern AJ. Modeling identical-by-descent haplotypes shows that the Erfurt founder event was more severe than expected based on reconstructions from modern AJ, implying substructure in medieval AJ whereby different groups have experienced different founder event intensities. Our results suggest that the AJ founder event and the acquisition of the main sources of AJ ancestry pre-dated the 14th century, while highlighting late medieval genetic heterogeneity no longer present in modern AJ.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006334","title":"Targeting the bicarbonate transporter SLC4A4 overcomes immunosuppression and immunotherapy resistance in pancreatic cancer","description":"Targeting the bicarbonate transporter SLC4A4 overcomes immunosuppression and immunotherapy resistance in pancreatic cancer","abstract":"Targeting the bicarbonate transporter SLC4A4 overcomes immunosuppression and immunotherapy resistance in pancreatic cancer","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-08T16:44:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006335","title":"Somatic_mutations_in_individuals_with_BAP1_germline_predispositions__Duplex_","description":"The process of how somatic mutation accumulate in the human lifecycle have only been started to be determined. Individuals with tumour predisposition syndromes, including germline deficiencies in the chromatin remodelling gene BAP1, have so far not been systematically investigated for the accumulation of somatic mutations. Furthermore, the rates at which somatic mutations accumulate, contributing to the development of mesotheliomas, renal cell carcinomas or uveal melanoma in these individuals have not been investigated. Here, we will collaborate with Michele Carbone, an internationally renown researcher in the area of mesothelioma and BAP1 germline predispositions to investigate the landscape of somatic mutations in DNA extracted from buccal swabs, blood as well as skin and cultured fibroblasts from live donors. To process these samples, we are using an ultra-high resolution sequencing method (Nanoseq) that was recently developed and patented in the group. Application of the method to these samples could result in findings with translational value for carriers of similar germline deficiencies.","abstract":"The process of how somatic mutation accumulate in the human lifecycle have only been started to be determined. Individuals with tumour predisposition syndromes, including germline deficiencies in the chromatin remodelling gene BAP1, have so far not been systematically investigated for the accumulation of somatic mutations. Furthermore, the rates at which somatic mutations accumulate, contributing to the development of mesotheliomas, renal cell carcinomas or uveal melanoma in these individuals have not been investigated. Here, we will collaborate with Michele Carbone, an internationally renown researcher in the area of mesothelioma and BAP1 germline predispositions to investigate the landscape of somatic mutations in DNA extracted from buccal swabs, blood as well as skin and cultured fibroblasts from live donors. To process these samples, we are using an ultra-high resolution sequencing method (Nanoseq) that was recently developed and patented in the group. Application of the method to these samples could result in findings with translational value for carriers of similar germline deficiencies.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006336","title":"Genomics of drug sensitivity in acute lymphoblastic leukemia","description":"Genomics of drug sensitivity in acute lymphoblastic leukemia","abstract":"Genomics of drug sensitivity in acute lymphoblastic leukemia","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-09T16:03:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006337","title":"HCA_WGS_Adult_Wellcome","description":"Human Cell Atlas - WGS Adult","abstract":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006338","title":"HCA_WGS_Foetal_Wellcome","description":"Human Cell Atlas - WGS Foetal","abstract":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006339","title":"Platelet RNAseq data for SLFN14 K219N patients","description":"Pathogenic missense variants in SLFN14, which encodes an RNA endoribonuclease protein that regulates rRNA degradation, are known to cause inherited thrombocytopenia with impaired platelet aggregation and ATP secretion. Despite rather mild laboratory defects, these patients display an obvious bleeding phenotype. The function of SLFN14 in megakaryocyte (MK) and platelet biology is unknown. This study aims to characterize the platelet transcriptome in patients with a SLFN14 K219N variant and model the disease in the immortalized megakaryocyte cell line imMKCL. Total platelet RNA was sequenced for two patients and 19 healthy controls. Differential gene expression analysis yielded a total of 2999 and 2888 significantly (|log2FC|&gt;1, FDR&lt;0.05) up- and downregulated genes, respectively. Remarkably, these downregulated genes were not enriched for any biological pathway while upregulated genes were enriched for pathways involved in (mitochondrial) translation and transcription with a significant upregulation of 134 ribosomal protein genes (RPG). Heterozygous and homozygous SLFN14 K219N imMKCL showed a defect in MK differentiation that aggravated during cell passaging of undifferentiated cells and in proplatelet formation. SLFN14 defective platelets and MK showed signs of rRNA degradation while this was absent in undifferentiated imMKCL cells. Upregulation of RPG through increased mTOR signaling in SLFN14 K219N MK seems to be a compensatory response for rRNA degradation. Indeed, mTOR inhibition with rapamycin resulted in further enhanced rRNA degradation in SLFN14 K219N MK. Taken together, our study indicates dysregulation of mTOR-regulated ribosomal biogenesis as the disease mechanism for SLFN14-related thrombocytopenia.","abstract":"Pathogenic missense variants in SLFN14, which encodes an RNA endoribonuclease protein that regulates rRNA degradation, are known to cause inherited thrombocytopenia with impaired platelet aggregation and ATP secretion. Despite rather mild laboratory defects, these patients display an obvious bleeding phenotype. The function of SLFN14 in megakaryocyte (MK) and platelet biology is unknown. This study aims to characterize the platelet transcriptome in patients with a SLFN14 K219N variant and model the disease in the immortalized megakaryocyte cell line imMKCL. Total platelet RNA was sequenced for two patients and 19 healthy controls. Differential gene expression analysis yielded a total of 2999 and 2888 significantly (|log2FC|&gt;1, FDR&lt;0.05) up- and downregulated genes, respectively. Remarkably, these downregulated genes were not enriched for any biological pathway while upregulated genes were enriched for pathways involved in (mitochondrial) translation and transcription with a significant upregulation of 134 ribosomal protein genes (RPG). Heterozygous and homozygous SLFN14 K219N imMKCL showed a defect in MK differentiation that aggravated during cell passaging of undifferentiated cells and in proplatelet formation. SLFN14 defective platelets and MK showed signs of rRNA degradation while this was absent in undifferentiated imMKCL cells. Upregulation of RPG through increased mTOR signaling in SLFN14 K219N MK seems to be a compensatory response for rRNA degradation. Indeed, mTOR inhibition with rapamycin resulted in further enhanced rRNA degradation in SLFN14 K219N MK. Taken together, our study indicates dysregulation of mTOR-regulated ribosomal biogenesis as the disease mechanism for SLFN14-related thrombocytopenia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-10T09:22:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006340","title":"Genetic and epigenetic variation at regulatory regions contribute to cancer evolution under endocrine treatment","description":"Comprehensive profiling of hormone-dependent breast cancer (HDBC) has identified hundreds of protein-coding alterations contributing to cancer initiation, but only a handful have been linked to endocrine therapy resistance, potentially contributing to 40% of relapses. If other mechanisms underlie the evolution of HDBC under adjuvant therapy is currently unknown. In this work, we employ integrative functional genomics to dissect the contribution of cis-regulatory elements (CREs) to cancer evolution by focusing on 12 megabases of non-coding DNA, including clonal enhancers, gene promoters, and boundaries of topologically associating domains. Massive parallel perturbation in vitro reveals context-dependent roles for many of these CREs, with a specific impact on dormancy entrance and endocrine therapy resistance9. Profiling of CRE somatic alterations in a unique, longitudinal cohort of patients treated with endocrine therapies identifies non-coding changes involved in therapy resistance. Overall, our data uncover actionable transient transcriptional programs critical for dormant persister cells and unveil new regulatory nodes driving evolutionary trajectories towards disease progression.","abstract":"Comprehensive profiling of hormone-dependent breast cancer (HDBC) has identified hundreds of protein-coding alterations contributing to cancer initiation, but only a handful have been linked to endocrine therapy resistance, potentially contributing to 40% of relapses. If other mechanisms underlie the evolution of HDBC under adjuvant therapy is currently unknown. In this work, we employ integrative functional genomics to dissect the contribution of cis-regulatory elements (CREs) to cancer evolution by focusing on 12 megabases of non-coding DNA, including clonal enhancers, gene promoters, and boundaries of topologically associating domains. Massive parallel perturbation in vitro reveals context-dependent roles for many of these CREs, with a specific impact on dormancy entrance and endocrine therapy resistance9. Profiling of CRE somatic alterations in a unique, longitudinal cohort of patients treated with endocrine therapies identifies non-coding changes involved in therapy resistance. Overall, our data uncover actionable transient transcriptional programs critical for dormant persister cells and unveil new regulatory nodes driving evolutionary trajectories towards disease progression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-10T10:50:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006341","title":"An analysis of the impact of TRAF3 high impact variants on B and T cell transcriptomes","description":null,"abstract":"Tumour necrosis factor receptor-associated factor 3 (TRAF3) is a central regulator of immunity, but its role in humans has not been fully defined. Transcriptomic analysis of patients with high impact variants in TRAF3, which resulted in haploinsufficiency, revealed increased activation of NF-KB2 pathway in B and T cells .","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006342","title":"Molecular determinants of outcomes in relapsed mantle cell lymphoma treated with ibrutinib or temsirolimus in the MCL3001 (RAY) trial","description":null,"abstract":"Mantle cell lymphoma (MCL) is a rare, incurable lymphoma subtype characterized by heterogeneous outcomes. In order to better understand the clinical behavior and response to treatment, powerful predictive biomarkers are needed. Using residual archived material from patients enrolled in the MCL3001 (RAY) study, we performed a detailed analysis of gene expression and genetic sequencing. This phase III clinical trial randomized patients with relapsed or refractory MCL to treatment with either ibrutinib or temsirolimus. We confirmed the prognostic capability of the RNA expression proliferation assay MCL35 in this cohort treated with novel agents, which outperformed the simplified MCL International Prognostic Index in discriminating patients with different outcomes. Regardless of treatment arm, we demonstrated that this assay captures the risk conferred by known biological factors, such as increased MYC-expression, blastoid morphology, aberrations of TP53, and truncated CCND1 3’untranslated region. We further showed the negative impact of BIRC3 mutations/deletions on outcomes in this cohort, and identified that deletion of chromosome 8p23.3 also has a deleterious effect on survival. Restricted to patients with deletions/alterations in TP53, ibrutinib appeared to abrogate the deleterious impact on outcome. These data illustrate the potential to perform a molecular analysis of predictive biomarkers from routine patient samples that can meaningfully inform clinical practice.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-10T17:17:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006343","title":"Single cell genomic variation induced by mutational processes in cancer","description":"How cell-to-cell copy number alterations that underpin genomic instability in human cancers drive genomic and phenotypic variation, and consequently cancer evolution, remains understudied. Here, applying scaled single cell whole genome sequencing to wildtype, TP53-deficient and TP53/BRCA1/2-deficient mammary epithelial cells (n=13,818 genomes) and primary triple negative breast (TNBC) and high grade serous ovarian cancers (HGSC) (n=22,057 genomes), we identified three distinct ‘foreground’ mutational patterns defined by cell-to-cell copy number and structural variation properties occurring in the ‘background’ of cancer-associated genomic instability. Cell and clone-specific high level amplifications (HLAMPs), parallel allele-specific copy number alterations and copy number segment length variation (serrate structural variations) exhibited measurable phenotypic and evolutionary consequences. Clone-specific HLAMPs in known oncogenes were highly prevalent in fold back inversion (FBI)-bearing tumors and associated with increased clone-to-clone phenotypic variation in gene expression inferred from matched single cell RNASeq. Parallel allele-specific alterations were linked with phylogenetically determined evolutionary diversity and clone-specific mono-allelic expression. Serrate patterns present across all clones were increased in FBI tumors, most prominently on a tetraploid background and were highly correlated with increased genomic diversity of cellular populations. Taken together, we show that cell-to-cell structural-copy number variation significantly impacts the phenotypes and evolutionary diversity of TNBC and HGSC, revealing previously hidden genomic states of cancer cells.","abstract":"How cell-to-cell copy number alterations that underpin genomic instability in human cancers drive genomic and phenotypic variation, and consequently cancer evolution, remains understudied. Here, applying scaled single cell whole genome sequencing to wildtype, TP53-deficient and TP53/BRCA1/2-deficient mammary epithelial cells (n=13,818 genomes) and primary triple negative breast (TNBC) and high grade serous ovarian cancers (HGSC) (n=22,057 genomes), we identified three distinct ‘foreground’ mutational patterns defined by cell-to-cell copy number and structural variation properties occurring in the ‘background’ of cancer-associated genomic instability. Cell and clone-specific high level amplifications (HLAMPs), parallel allele-specific copy number alterations and copy number segment length variation (serrate structural variations) exhibited measurable phenotypic and evolutionary consequences. Clone-specific HLAMPs in known oncogenes were highly prevalent in fold back inversion (FBI)-bearing tumors and associated with increased clone-to-clone phenotypic variation in gene expression inferred from matched single cell RNASeq. Parallel allele-specific alterations were linked with phylogenetically determined evolutionary diversity and clone-specific mono-allelic expression. Serrate patterns present across all clones were increased in FBI tumors, most prominently on a tetraploid background and were highly correlated with increased genomic diversity of cellular populations. Taken together, we show that cell-to-cell structural-copy number variation significantly impacts the phenotypes and evolutionary diversity of TNBC and HGSC, revealing previously hidden genomic states of cancer cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-10T20:43:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006344","title":"Placebo-only arm transcriptomic analysis of the phase 3 PROTECT clinical trial","description":"It is poorly understood how the tumor immune microenvironment influences disease recurrence in localized clear cell renal cell carcinoma (ccRCC). Here we perform whole-transcriptomic profiling of 236 tumors from patients assigned to the placebo-only arm of a randomized, adjuvant clinical trial for high-risk localized ccRCC. Unbiased pathway analysis identifies myeloid-derived interleukin-6 (IL-6) as a key mediator. Furthermore, a novel myeloid gene signature strongly correlates with disease recurrence and overall survival on uni- and multivariate analysis and is linked to TP53 inactivation across multiple datasets.","abstract":"It is poorly understood how the tumor immune microenvironment influences disease recurrence in localized clear cell renal cell carcinoma (ccRCC). Here we perform whole-transcriptomic profiling of 236 tumors from patients assigned to the placebo-only arm of a randomized, adjuvant clinical trial for high-risk localized ccRCC. Unbiased pathway analysis identifies myeloid-derived interleukin-6 (IL-6) as a key mediator. Furthermore, a novel myeloid gene signature strongly correlates with disease recurrence and overall survival on uni- and multivariate analysis and is linked to TP53 inactivation across multiple datasets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-13T13:33:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006345","title":"Genetic regulation of gene expression in human brain cell types","description":"We leveraged single nuclei RNA-seq from 192 human brain samples to map cis-eQTLs in 8 brain cell types. We found extensive cell-type specific genetic effect on gene expression and integrated our results with GWAS to identify putative novel risk genes for brain disorders and the cell types in which the disease mechanisms are likely active.","abstract":"We leveraged single nuclei RNA-seq from 192 human brain samples to map cis-eQTLs in 8 brain cell types. We found extensive cell-type specific genetic effect on gene expression and integrated our results with GWAS to identify putative novel risk genes for brain disorders and the cell types in which the disease mechanisms are likely active.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-14T08:59:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006346","title":"Clonal_dynamics_and_mutation_burden_in_male_germline_","description":"This work aim to study clonal dynamics of pathogenic mutations in male germline. Using Nanoseq method, sperm from normal panel will be compared with sperm from men who have either clinical phynotypes or they have child(ren) with germline predisposition syndromes.","abstract":"Inherited cancers play a major role in about 5 to 10 percent of all cancers. It is increasingly apparent that many inherited cancer syndromes arise through new mutations acquired most likely in germline of fathers. Most of the burden of high-penetrance germline predisposition to cancer arises through mutations acquired during spermatogenesis. However, little is known about mutagenesis within the hierarchy of spermatogenesis or factors that influence rates of mutation in the testes. It is likely that mutations in spermatogonia stem cells that confer weaker selective advantage and generate smaller clonal expansions in the testes, become enrich in sperms and transmit to the next generations. However, due to the low sensitivity of standard genomic approaches, subclonal mutations that may only be present in small contiguous areas within testes have been poorly investigated.  \n\nThis proposal aims to measure the mutational burden of pathogenic variants in sperms and to identify the processes that underlie their acquisition.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-14T10:03:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006347","title":"Single cell whole genome sequencing of high hyperdiploid acute lymphoblastic leukemia","description":"This dataset was collected from viable bone marrow cells obtained at diagnosis from nine patients with high hyperdiploid ALL and one normal bone marrow sample. All samples were subjected to low pass single cell whole genome sequencing with the median sequencing coverage of 0.02x. Single nuclei in G0/G1 phase were isolated using a fluorescence-activated cell sorting (FACS) cytometer. DNA libraries were constructed and associated next-generation sequencing was carried out by European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Further details regarding the DNA libraries construction are available by Bos et. al., 2019 (https://link.springer.com/protocol/10.1007/978-1-4939-8931-7_15). The dataset has been used for copy number aberrations analysis.","abstract":"This dataset was collected from viable bone marrow cells obtained at diagnosis from nine patients with high hyperdiploid ALL and one normal bone marrow sample. All samples were subjected to low pass single cell whole genome sequencing with the median sequencing coverage of 0.02x. Single nuclei in G0/G1 phase were isolated using a fluorescence-activated cell sorting (FACS) cytometer. DNA libraries were constructed and associated next-generation sequencing was carried out by European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Further details regarding the DNA libraries construction are available by Bos et. al., 2019 (https://link.springer.com/protocol/10.1007/978-1-4939-8931-7_15). The dataset has been used for copy number aberrations analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-14T10:41:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006348","title":"The admixture histories of Cabo Verde","description":null,"abstract":"From the 15th to the 19th century, the Trans-Atlantic Slave-Trade influenced the genetic and cultural diversity of numerous populations. We explore genomic and linguistic data from the nine islands of Cabo Verde, the earliest European colony of the era in Africa, a major Slave-Trade platform between the 16th and 19th centuries, and a previously uninhabited location ideal for investigating early admix-ture events between Europeans and Africans. We find that genetic admixture in Cabo Verde occurred primarily between Iberian and Senegambian populations, although forced and voluntary migrations to the archipelago involved numerous other populations. Inter-individual genetic and linguistic variation recapitulate geographic distribution of individuals’ birth-places across Cabo Verdean islands, suggest-ing that Kriolu language variants have developed together with genetic divergences. Furthermore, we find that admixture occurred both early in each island, long before the 18th-century massive TAST deportations triggered by the expansion of plantation economy in Africa and the Americas, and after this era mostly during the abolition of the TAST and of slavery in European colonial empires. Our results illustrate how shifting socio-cultural relationships between enslaved and non-enslaved commu-nities shaped enslaved-African descendants’ genomic diversity and structure on both sides of the Atlantic.\n\"The genetic and linguistic admixture histories of the islands of Cabo Verde\" by Laurent R et al. eLife 2023 (DOI: https://doi.org/10.7554/eLife.79827 - URL: https://elifesciences.org/articles/79827)","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-14T18:14:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006349","title":"Targeted sequencing of mutation hotspots in urine cell-pellet DNA for bladder cancer genes","description":null,"abstract":"Targeted sequencing of mutation hotspots in urine cell-pellet DNA was performed for 28 bladder cancer associated genes, on a total of 884 specimens. Of the total set, n=690 represented bladder cancer negative specimens, and n=194 were bladder cancer positive specimens.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006350","title":"molecular profiles of serum-derived extracellular vesicles in high-grade serous ovarian cancer","description":"Patients with high-grade serous ovarian cancer (HGSC) who have no visible residual disease (R0) after primary surgery have the best clinical outcomes, followed by patients who undergo neoadjuvant chemotherapy (NACT) and have response enabling interval cytoreductive surgery. Clinically useful predictive biomarkers for such distinctions are still lacking. Extracellular vesicles (EVs) have been recognized as liquid biopsy-based biomarkers for early cancer detection and disease surveillance in other disease settings. In this study, we performed extensive molecular characterization of serum-derived EVs and correlated them with therapeutic outcomes in patients with HGSC.","abstract":"Patients with high-grade serous ovarian cancer (HGSC) who have no visible residual disease (R0) after primary surgery have the best clinical outcomes, followed by patients who undergo neoadjuvant chemotherapy (NACT) and have response enabling interval cytoreductive surgery. Clinically useful predictive biomarkers for such distinctions are still lacking. Extracellular vesicles (EVs) have been recognized as liquid biopsy-based biomarkers for early cancer detection and disease surveillance in other disease settings. In this study, we performed extensive molecular characterization of serum-derived EVs and correlated them with therapeutic outcomes in patients with HGSC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-14T21:18:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006351","title":"Rhabdoid tumor sequencing data","description":"This study contains sequencing DNA and RNA sequencing data for rhabdoid tumors","abstract":"This study contains sequencing DNA and RNA sequencing data for rhabdoid tumors","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-15T00:35:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006352","title":"Brain tumor sequencing data","description":"This study contains tumor DNA (with matched normal) for 1 medulloblastoma and 1 ependymoma patient. Tumor RNA sequencing data is also present for the medulloblastoma patient","abstract":"This study contains tumor DNA (with matched normal) for 1 medulloblastoma and 1 ependymoma patient. Tumor RNA sequencing data is also present for the medulloblastoma patient","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-15T00:35:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006353","title":"Diffuse Intrinsic Pontine Glioma","description":"This study contains DNA and RNA sequencing data for 5 DIPG patients. All patients have tumor DNA data, 4 have matched normal DNA data and 3 have tumor RNA seq data","abstract":"This study contains DNA and RNA sequencing data for 5 DIPG patients. All patients have tumor DNA data, 4 have matched normal DNA data and 3 have tumor RNA seq data","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-15T00:35:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006354","title":"Acute myeloid leukemia sequencing data","description":"This study contains tumor DNA and RNA sequencing data for 1 AML patient","abstract":"This study contains tumor DNA and RNA sequencing data for 1 AML patient","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-15T00:35:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006355","title":"Glioma sequencing data","description":"This study contains sequencing data for various glioma subtypes (astrocytoma, glioblastoma, diffuse midline glioma).","abstract":"This study contains sequencing data for various glioma subtypes (astrocytoma, glioblastoma, diffuse midline glioma).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-15T00:35:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006356","title":"Soft tissue sarcoma sequencing data","description":null,"abstract":"This study contains DNA and RNA sequencing data for various soft tissue sarcomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-15T00:35:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006357","title":"early-Duodenal Cancer sequencing study","description":"...","abstract":"...","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-15T05:54:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006358","title":"Clonal dominance defines metastatic dissemination in pancreatic cancer","description":"Using patient-derived cells from a pancreatic ductal adenocarcinoma, we created orthotopic clonal replica tumors to trace in an unbiased fashion clonal lineage dynamics of unperturbed tumor expansion and dissemination over time. The model revealed the complex multifaced nature of tumor clonal expansion and uncovered brisk changes in fitness that lead to a continuous reshuffling of tumor clonal architecture and alternating clonal dominance as a distinct feature of cancer growth. Paired analysis of clonal lineages in primary and secondary sites revealed fitness in the primary tumor as a major contributor to dissemination, although other clonal intrinsic and extrinsic factors may contribute to metastatic process. Molecular characterization of lineages with differential metastatic potential identified actionable strategy to suppress dissemination at the subclonal level.","abstract":"Using patient-derived cells from a pancreatic ductal adenocarcinoma, we created orthotopic clonal replica tumors to trace in an unbiased fashion clonal lineage dynamics of unperturbed tumor expansion and dissemination over time. The model revealed the complex multifaced nature of tumor clonal expansion and uncovered brisk changes in fitness that lead to a continuous reshuffling of tumor clonal architecture and alternating clonal dominance as a distinct feature of cancer growth. Paired analysis of clonal lineages in primary and secondary sites revealed fitness in the primary tumor as a major contributor to dissemination, although other clonal intrinsic and extrinsic factors may contribute to metastatic process. Molecular characterization of lineages with differential metastatic potential identified actionable strategy to suppress dissemination at the subclonal level.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-15T20:20:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006359","title":"HCA_Heart_Adult_Wellcome_DNA","description":"Human Cell Atlas - WGS Adult Heart","abstract":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetic and genomic analysis, expression analysis, non-identifiable video imaging, and cell line and organoid production as well as computational algorithms to predict cellular developmental trajectories and cell-cell interactions.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-16T08:35:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006360","title":"HCA_Amnion_RNA","description":"Using single-cell and spatial genomics methods to interogate amnion profiles - The amnion is an essential membrane surrounding the embryo. In primates, the epiblast differentiates into the amniotic ectoderm, which goes on to form part of the amnion proper. However, given the primate-specific nature of this tissue, very little is understood as to the mechanisms of its specification and maturation. Here, we will characterise the human amnion from donated fetal samples for the first time. By defining the key markers and expression patterns of this tissue, we will provide a valuable resource for both embryological knowledge and markers to define and develop in vitro systems.","abstract":"Using single-cell and spatial genomics methods to interogate amnion profiles.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006361","title":"Subgroup-specific gene expression profiles and mixed epistasis in chronic lymphocytic leukemia (HIPO, H005)","description":null,"abstract":"Despite the extensive catalogue of recurrent mutations in chronic lymphocytic leukaemia (CLL), molecular driving events and the resulting range of disease phenotypes remain incompletely understood. To study the molecular heterogeneity of CLL, we performed RNA-sequencing on 184 CLL patient samples (H005). Unsupervised analysis revealed two major orthogonal axes of gene expression variation: the first one represented the mutational status of the immunoglobulin heavy variable (IGHV) genes, and concomitantly, the three-group stratification of CLL by global DNA methylation. The second axis aligned with trisomy 12 status and affected chemokine, MAPK and mTOR signaling. We discovered non-additive effects (epistasis) of IGHV mutation status and trisomy 12 on multiple phenotypes, including the expression of 893 genes and ex-vivo drug responses. Multiple types of epistasis were observed, including synergy, buffering, suppression and inversion, suggesting that molecular understanding of disease heterogeneity requires studying them together. We searched for differentially expressed genes associated with major gene mutations and copy-number aberrations and detected strong signatures for SF3B1, BRAF and TP53, as well as del(17)(p13), del(13)(q14) and del(11)(q22.3) beyond dosage effect. \nOur study reveals previously underappreciated gene expression signatures for (epi)genomic variants in CLL and the presence of epistasis between them.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-17T15:15:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006362","title":"Juntendo Muscle Study (JMS)","description":"Skeletal muscle fiber type distribution has implications for human health, muscle function and performance. This knowledge has been gathered using labor intensive and costly methodology that limited these studies. This data was used to present a new method based on muscle tissue RNA sequencing data to estimate the distribution of skeletal muscle fiber types from frozen human samples, allowing for larger number of individuals to be tested in a cost and labor efficient way. Muscle biopsies were taken from the vastus lateralis muscle of 23 human subjects from Japan. Samples were sequenced on the NextSeq® 500/550 (Illumina).","abstract":"Skeletal muscle fiber type distribution has implications for human health, muscle function and performance. This knowledge has been gathered using labor intensive and costly methodology that limited these studies. This data was used to present a new method based on muscle tissue RNA sequencing data to estimate the distribution of skeletal muscle fiber types from frozen human samples, allowing for larger number of individuals to be tested in a cost and labor efficient way. Muscle biopsies were taken from the vastus lateralis muscle of 23 human subjects from Japan. Samples were sequenced on the NextSeq® 500/550 (Illumina).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-17T16:06:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006363","title":"Muscle SATellite cell study (MSAT)","description":"Skeletal muscle fiber type distribution has implications for human health, muscle function and performance. This knowledge has been gathered using labor-intensive and costly methodology that limited these studies. This data was used to present a new method based on muscle tissue RNA sequencing data to estimate the distribution of skeletal muscle fiber types from frozen human samples, allowing for larger number of individuals to be tested in a cost and labor efficient way. Muscle biopsies were taken from the vastus lateralis muscle of 39 Swedish male subjects. Samples were sequenced on the NextSeq® 500/550 (Illumina).","abstract":"Skeletal muscle fiber type distribution has implications for human health, muscle function and performance. This knowledge has been gathered using labor-intensive and costly methodology that limited these studies. This data was used to present a new method based on muscle tissue RNA sequencing data to estimate the distribution of skeletal muscle fiber types from frozen human samples, allowing for larger number of individuals to be tested in a cost and labor efficient way. Muscle biopsies were taken from the vastus lateralis muscle of 39 Swedish male subjects. Samples were sequenced on the NextSeq® 500/550 (Illumina).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-17T16:06:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006364","title":"Single-cell multi-omics of human clonal hematopoiesis reveals that DNMT3A R882 mutations perturb early progenitor states through selective hypomethylation.","description":null,"abstract":"Somatic mutations in cancer genes have been ubiquitously detected in clonal expansions across healthy human tissue, including in clonal hematopoiesis. However, mutated and wildtype cells are morphologically and phenotypically similar, limiting the ability to link genotypes with cellular phenotypes. To overcome this limitation, we leveraged multi-modality single-cell sequencing, capturing the mutation with transcriptomes and methylomes in progenitors from individuals with DNMT3A R882 mutated clonal hematopoiesis. DNMT3A mutations resulted in myeloid over lymphoid bias, and in expansion of immature myeloid progenitors primed toward megakaryocytic-erythroid fate. We observed dysregulated expression of lineage and leukemia stem cell markers. DNMT3A R882 led to preferential hypomethylation of polycomb repressive complex 2 targets and a specific sequence motif. Notably, the hypomethylation motif is enriched in binding motifs of key hematopoietic transcription factors, serving as a potential mechanistic link between DNMT3A R882 mutations and aberrant transcriptional phenotypes. Thus, single-cell multi-omics pave the road to defining the downstream consequences of mutations that drive human clonal mosaicism.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-17T18:40:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006365","title":"Widespread hypertranscription in aggressive human cancers","description":"Cancers are often defined by the dysregulation of specific transcriptional programs; however, the importance of global transcriptional changes is less understood. Hypertranscription is the genome-wide increase in RNA output. Hypertranscription’s prevalence, underlying drivers and prognostic significance are undefined in primary human cancer. This is due in part to limitations of expression profiling methods, which assume equal RNA output between samples. Here, we developed a computational method to directly measure hypertranscription in 7,494 human tumors, spanning 31 cancer types. Hypertranscription is ubiquitous across cancer, especially in aggressive disease. It defines patient subgroups with worse survival, even within well-established subtypes. Our data suggest that loss of transcriptional suppression underpins the hypertranscriptional phenotype. Single-cell analysis reveals hypertranscriptional clones, which dominate transcript production regardless of their size. Finally, patients with hypertranscribed mutations have improved response to immune checkpoint therapy. Our results provide fundamental insights into gene dysregulation across human cancers and may prove useful in identifying patients that would benefit from novel therapies.","abstract":"Cancers are often defined by the dysregulation of specific transcriptional programs; however, the importance of global transcriptional changes is less understood. Hypertranscription is the genome-wide increase in RNA output. Hypertranscription’s prevalence, underlying drivers and prognostic significance are undefined in primary human cancer. This is due in part to limitations of expression profiling methods, which assume equal RNA output between samples. Here, we developed a computational method to directly measure hypertranscription in 7,494 human tumors, spanning 31 cancer types. Hypertranscription is ubiquitous across cancer, especially in aggressive disease. It defines patient subgroups with worse survival, even within well-established subtypes. Our data suggest that loss of transcriptional suppression underpins the hypertranscriptional phenotype. Single-cell analysis reveals hypertranscriptional clones, which dominate transcript production regardless of their size. Finally, patients with hypertranscribed mutations have improved response to immune checkpoint therapy. Our results provide fundamental insights into gene dysregulation across human cancers and may prove useful in identifying patients that would benefit from novel therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-17T19:25:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006366","title":"Chromatin immunoprecipitation followed by sequencing combined with transcription factor (TF) motif identification and transcriptome analyses revealed different patterns of REST binding and its proximal TF motifs in IDH wild-type and mutant gliomas","description":null,"abstract":"We studied consequences of REST knockdown in IDH wild-type and mutant U87 cells. Chromatin immunoprecipitation followed by sequencing combined with transcription factor (TF) motif identification and transcriptome analyses revealed different patterns of REST binding and its proximal TF motifs in IDH wild-type and mutant U87 cells. Moreover, we identified putative targets of  REST as related to ECM organization and cell differentiation.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006367","title":"Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis","description":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","abstract":"To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF&lt;5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A&gt;T, p.(Lys3326Ter)BRCA2 p.Lys332X variant,  which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G&gt;A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006368","title":"Allelic overload and its clinical modifier effect in Bardet-Biedl syndrome","description":null,"abstract":"ardet-Biedl syndrome (BBS, MIM #209900) is a clinically and genetically heterogeneous rare multisystemic disease. BBS is usually inherited as an autosomal recessive Mendelian trait with variable intra- and inter-familial severity. The penetrance and/or phenotypic expressivity of causative biallelic BBS variants are modulated in some families by the presence of oligogenic modifiers. In those families, a third mutation in a second gene has been correlated with an earlier onset or a more severe specific phenotype in the carrier BBS patients due to a probable modifying effect. The goal of this project focuses on establishing and understanding new potential oligogenic combinations that may explain the clinical variability in BBS-affected families.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006369","title":"RNA-seq analysis of metastatic prostate cancer solid tumor biopsies","description":"The prevalence and features of treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC) are not well characterized in the era of modern androgen receptor (AR)–targeting therapy. We sought to characterize the clinical and genomic features of t-SCNC in a multi-institutional prospective study. Patients with progressive, metastatic castration-resistant prostate cancer (mCRPC) underwent metastatic tumor biopsy and were followed for survival. t-SCNC is present in nearly one fifth of patients with mCRPC and is associated with shortened survival.","abstract":"The prevalence and features of treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC) are not well characterized in the era of modern androgen receptor (AR)–targeting therapy. We sought to characterize the clinical and genomic features of t-SCNC in a multi-institutional prospective study. Patients with progressive, metastatic castration-resistant prostate cancer (mCRPC) underwent metastatic tumor biopsy and were followed for survival. t-SCNC is present in nearly one fifth of patients with mCRPC and is associated with shortened survival.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-20T19:02:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006370","title":"Transcriptome sequencing in monozygotic twins discordant for Mayer-Rokitansky-Küster-Hauser syndrome","description":null,"abstract":"In this study, we sought to identify differences in gene expression between sporadic cases of Mayer-Rokitansky-Küster-Hauser syndrome and affected individuals of monozygotic discordant twins using transcriptome sequencing of rudiment uterine tissue.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-20T21:44:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006371","title":"Genome sequencing in monozygotic twins discordant for Mayer-Rokitansky-Küster-Hauser syndrome","description":null,"abstract":"In this study, we sought to identify the genetic causes of Mayer-Rokitansky-Küster-Hauser syndrome in monozygotic discordant twins using whole genome sequencing of blood of twin pairs as well as uterine tissue of the affected twins.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-20T21:44:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006372","title":"Presence of rare potential pathogenic variants in subjects under 65 years old with very severe or fatal COVID‑19","description":"Rare variants affecting host defense against pathogens could be involved in COVID‑19 severity and\nmay help explain fatal outcomes in young and middle‑aged patients. Our aim was to report the\npresence of rare genetic variants in certain genes, by using whole exome sequencing, in a selected\ngroup of COVID‑19 patients under 65 years who required intubation or resulting in death (n = 44).\nTo this end, different etiopathogenic mechanisms were explored using gene prioritization‑based\nanalysis in which genes involved in immune response, immunodeficiencies or blood coagulation\nwere studied. We detected 44 different variants of interest, in 29 different patients (66%). Some of\nthese variants were previously described as pathogenic and were located in genes mainly involved\nin immune response. A network analysis, including the 42 genes with candidate variants, showed\nthree main components, consisting of 25 highly interconnected genes related to immune response\nand two additional networks composed by genes enriched in carbohydrate metabolism and in DNA\nmetabolism and repair processes. In conclusion, we have detected candidate variants that may\npotentially influence COVID‑19 outcome in our cohort of patients. Further studies are needed to\nconfirm the ultimate role of the genetic variants described in the present study on COVID‑19 severity.","abstract":"Rare variants affecting host defense against pathogens could be involved in COVID‑19 severity and\nmay help explain fatal outcomes in young and middle‑aged patients. Our aim was to report the\npresence of rare genetic variants in certain genes, by using whole exome sequencing, in a selected\ngroup of COVID‑19 patients under 65 years who required intubation or resulting in death (n = 44).\nTo this end, different etiopathogenic mechanisms were explored using gene prioritization‑based\nanalysis in which genes involved in immune response, immunodeficiencies or blood coagulation\nwere studied. We detected 44 different variants of interest, in 29 different patients (66%). Some of\nthese variants were previously described as pathogenic and were located in genes mainly involved\nin immune response. A network analysis, including the 42 genes with candidate variants, showed\nthree main components, consisting of 25 highly interconnected genes related to immune response\nand two additional networks composed by genes enriched in carbohydrate metabolism and in DNA\nmetabolism and repair processes. In conclusion, we have detected candidate variants that may\npotentially influence COVID‑19 outcome in our cohort of patients. Further studies are needed to\nconfirm the ultimate role of the genetic variants described in the present study on COVID‑19 severity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-21T09:13:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006373","title":"Longitudinal ctDNA in Uveal Melanoma","description":"Assess the efficacy of using multi-modal ctDNA analysis to detect relapse in patients with uveal melanoma","abstract":"Assess the efficacy of using multi-modal ctDNA analysis to detect relapse in patients with uveal melanoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-21T18:02:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006374","title":"Pathogenic  variants  damage cell compositions and single cell transcription in cardiomyopathies","description":"Pathogenic variants in genes that cause dilated (DCM) and arrhythmogenic cardiomyopathies (ACM) convey high risks for the development of heart failure (HF) through unknown mechanisms. Using single nucleus RNA sequencing (snRNAseq), we characterized the transcriptome of 880,000 nuclei from 18 control and 61 failing, non-ischemic human hearts with pathogenic variants in DCM and ACM genes or idiopathic disease. We performed genotype-stratified analyses of the ventricular cell lineages and transcriptional states. The resultant DCM and ACM ventricular cell atlas demonstrated distinct right and left ventricular responses, highlighting genotype-associated pathways, intercellular interactions, and differential gene expression at single cell resolution. Together these data illuminate both shared and distinct cellular and molecular architectures of human HF and suggest novel candidate therapeutic targets.","abstract":"Pathogenic variants in genes that cause dilated (DCM) and arrhythmogenic cardiomyopathies (ACM) convey high risks for the development of heart failure (HF) through unknown mechanisms. Using single nucleus RNA sequencing (snRNAseq), we characterized the transcriptome of 880,000 nuclei from 18 control and 61 failing, non-ischemic human hearts with pathogenic variants in DCM and ACM genes or idiopathic disease. We performed genotype-stratified analyses of the ventricular cell lineages and transcriptional states. The resultant DCM and ACM ventricular cell atlas demonstrated distinct right and left ventricular responses, highlighting genotype-associated pathways, intercellular interactions, and differential gene expression at single cell resolution. Together these data illuminate both shared and distinct cellular and molecular architectures of human HF and suggest novel candidate therapeutic targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-22T12:34:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006375","title":"An Atlas of Cells in the Human Tonsil","description":"Palatine tonsils are secondary lymphoid organs representing the first line of immunological defense against inhaled or ingested pathogens. Here, we provide a comprehensive census of cell types forming the human tonsil by applying single cell transcriptome, epigenome, proteome and adaptive immune repertoire as well as spatial transcriptomics, resulting in an atlas of &gt;350,000 cells. We provide a glossary of over one hundred annotated cell types and states, and disentangle gene regulatory mechanisms that drive cells through specialized lineage trajectories. Exemplarily, we stratify multiple tonsil-resident myeloid slancyte subtypes, establish a distant BCL6 superenhancer as locally active in both follicle-associated T and B cells, and describe SIX5 as a potentially novel transcriptional regulator of plasma cell maturation. Further, our atlas is  a reference map to understand  alterations observed in disease, here we discover immune-phenotype plasticity in tumoral cells and microenvironment shifts of mantle cell lymphomas (MCL). To facilitate such reference-based analysis, we develop HCATonsilData and SLOcatoR, a computational framework that provides programmatic and modular access to our dataset; and allows the straightforward annotation of future single-cell profiles from secondary lymphoid organs.","abstract":"Palatine tonsils are secondary lymphoid organs representing the first line of immunological defense against inhaled or ingested pathogens. Here, we provide a comprehensive census of cell types forming the human tonsil by applying single cell transcriptome, epigenome, proteome and adaptive immune repertoire as well as spatial transcriptomics, resulting in an atlas of &gt;350,000 cells. We provide a glossary of over one hundred annotated cell types and states, and disentangle gene regulatory mechanisms that drive cells through specialized lineage trajectories. Exemplarily, we stratify multiple tonsil-resident myeloid slancyte subtypes, establish a distant BCL6 superenhancer as locally active in both follicle-associated T and B cells, and describe SIX5 as a potentially novel transcriptional regulator of plasma cell maturation. Further, our atlas is  a reference map to understand  alterations observed in disease, here we discover immune-phenotype plasticity in tumoral cells and microenvironment shifts of mantle cell lymphomas (MCL). To facilitate such reference-based analysis, we develop HCATonsilData and SLOcatoR, a computational framework that provides programmatic and modular access to our dataset; and allows the straightforward annotation of future single-cell profiles from secondary lymphoid organs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-22T13:04:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006376","title":"SARS-CoV-2 host genetics and COVID-19 outcomes in admixed Brazilians with extreme phenotypes","description":"COVID-19 comprises clinical outcomes of SARS-CoV-2 infection and is highly heterogeneous, ranging from asymptomatic individuals to deceased young adults without comorbidities. There is growing evidence that host genetics play an important role in COVID-19 severity, including inborn errors of immunity, age-related inflammation and immunosenescence. This study proposes a strategy of subject’s ascertainment based on phenotypic extremes to take part in genomic studies and elucidate intrinsic risk factors involved in COVID-19 severe outcomes. Different cohorts were collected and submitted to Next-Generation Sequencing (Whole exome and whole genome sequencing).","abstract":"COVID-19 comprises clinical outcomes of SARS-CoV-2 infection and is highly heterogeneous, ranging from asymptomatic individuals to deceased young adults without comorbidities. There is growing evidence that host genetics play an important role in COVID-19 severity, including inborn errors of immunity, age-related inflammation and immunosenescence. This study proposes a strategy of subject’s ascertainment based on phenotypic extremes to take part in genomic studies and elucidate intrinsic risk factors involved in COVID-19 severe outcomes. Different cohorts were collected and submitted to Next-Generation Sequencing (Whole exome and whole genome sequencing).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-22T15:17:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006377","title":"Plasma whole genome sequencing from patients with stage IV colorectal cancer and microsatellite instability","description":"This study aims to explore genomic features of cancer in plasma WGS data from patients with advanced colorectal cancer. Cell-free DNA (cfDNA) was extracted from plasma using the QIAamp Circulating Nucleic Acid Kit. Libraries were prepared with 5 to 250 ng of cfDNA using the NEBNext DNA Library Prep Kit.","abstract":"This study aims to explore genomic features of cancer in plasma WGS data from patients with advanced colorectal cancer. Cell-free DNA (cfDNA) was extracted from plasma using the QIAamp Circulating Nucleic Acid Kit. Libraries were prepared with 5 to 250 ng of cfDNA using the NEBNext DNA Library Prep Kit.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-22T15:39:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006378","title":"Whole genome landscape of 25 metastatic cutaneous squamous cell carcinoma cSCC patients","description":"whole genome sequencing on lymph node metastases and blood DNA from 25 cSCC patients with regional metastases of the head and neck. We designed a multifaceted computational analysis at the whole genome level to provide a more comprehensive perspective of the genomic landscape of metastatic cSCC. This study contains the majority of 15 samples which are previously submitted in  EGAC00001001100.","abstract":"whole genome sequencing on lymph node metastases and blood DNA from 25 cSCC patients with regional metastases of the head and neck. We designed a multifaceted computational analysis at the whole genome level to provide a more comprehensive perspective of the genomic landscape of metastatic cSCC. This study contains the majority of 15 samples which are previously submitted in  EGAC00001001100.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-23T13:28:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006379","title":"Genetic_Determinants_of_the_Transcriptomic_Immune_Trajectory_During_Pregnancy","description":"During pregnancy the maternal immune system must maintain a balance between tolerating the developing fetus and preserving mechanisms for protection against infection. Symptoms of autoimmune diseases such as rheumatoid arthritis can alleviate during pregnancy and flare following delivery, suggesting that understanding the modulation of the immune system during pregnancy could be informative for understanding autoimmune disease mechanisms. The maternal immune system is known to change during pregnancy, shifting from a pro-inflammatory (first trimester) to an anti-inflammatory state (second trimester) and finally to renewed inflammation (third trimester) (Mor et al. 2010). There have been few previous studies measuring the maternal systemic transcriptomic response during pregnancy, but those that have been conducted provide some molecular data supporting the observed functional changes in the maternal immune system. The majority of these previous studies have been conducted on small cohorts (10s of patients) (Weix et al. 2012, Mittal et al. 2015, Knight et al. 2018) but a recent study in Japan has recruited ~300 women and collected samples for RNA at three time points (2nd trimester, 3rd trimester and 1 month after delivery) (Sugawara et al. 2019). With cohorts of 100s of individuals, eQTL mapping can be used to highlight specific variants that may contribute to how the maternal immune system responds to the different stages of pregnancy and therefore the role of genetics in shaping the immune trajectory. The Pregnancy Outcome Prediction Study (POPs2) will be recruiting a second cohort of 4,000 (plus 250 samples recruited before study was suspended due COVID19) women at the Rosie Hospital, Cambridge starting in January 2020. Blood is collected at weeks 12, 20, 28 and 36 in addition to DNA samples (mother, father and baby), placenta biopsies and cord blood. We propose to include a PAXgene tube during the blood collection in addition to the currently established sampling, which would provide a unique opportunity to profile the maternal transcriptomic response during pregnancy and integrate it with genetic data. We propose generating genotyping and bulk RNAsequencing data from maternal whole blood across the four time points for the first 1,250 women. This would allow the following questions to be addressed: - Which genes are differentially expressed across pregnancy and how variable are they across the cohort? - Which DNA variants are associated with altered expression of a gene (eQTL)? - Which eQTLs are being modified (either magnified or dampened) over time during pregnancy? We propose to conduct an analysis while recruitment is ongoing (for example the first 100 women with four completed time points) to assess whether all four time points are necessary, or if the sampling strategy can be adjusted to cover fewer time points but a greater proportion of the cohort. This study design will allow us to identify which eQTL effects are being modified (either magnified or dampened) by an environmental perturbation (i.e. pregnancy) in vivo. These in vivo Eqtl interactions will give us insight into the regulatory mechanisms responsible for the modulation of the immune response during pregnancy, and could therefore be informative for identifying new drug targets for immune modulation therapies. This proposed project will complement the ongoing cellular mapping of immune cells in the environment of the maternal-foetal interface during pregnancy being conducted by the Vento-Tormo group (CellGen). Blood samples for Genotyping will be sent directly to the genotyping facility outsourced.","abstract":"We are generating bulk RNA-sequencing data from maternal whole blood across the four time points for 1,000 women. This would allow us to determine which genes are differentially expressed across pregnancy and how variable are they across the cohort.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006380","title":"Bulk-tissue RNA-sequencing paired nuclear and cytoplasmic fractions of anterior prefrontal cortex, cerebellar cortex and putamen tissues from post-mortem neuropathologically-confirmed control individuals.","description":"Gaining insight into the genetic regulation of gene expression in human brain is key to the interpretation of genome-wide association studies for major neurological and neuropsychiatric diseases. Expression quantitative trait loci (eQTL) analyses have largely been used to achieve this, providing valuable insights into the genetic regulation of steady-state RNA in human brain, but not distinguishing between molecular processes regulating transcription and stability. RNA quantification within cellular fractions can disentangle these processes in cell types and tissues which are challenging to model in vitro. We investigated the underlying molecular processes driving the genetic regulation of gene expression specific to a cellular fraction using allele-specific expression (ASE). Applying ASE analysis to genomic and transcriptomic data from paired nuclear and cytoplasmic fractions of anterior prefrontal cortex, cerebellar cortex and putamen tissues from 4 post-mortem neuropathologically-confirmed control human brains, we demonstrate that a significant proportion of genetic regulation of gene expression occurs post-transcriptionally in the cytoplasm, with genes undergoing this form of regulation more likely to be synaptic. These findings have implications for understanding the structure of gene expression regulation in human brain, and importantly the interpretation of rapidly growing single-nucleus brain RNA-sequencing and eQTL datasets, where cytoplasm-specific regulatory events could be missed.","abstract":"Gaining insight into the genetic regulation of gene expression in human brain is key to the interpretation of genome-wide association studies for major neurological and neuropsychiatric diseases. Expression quantitative trait loci (eQTL) analyses have largely been used to achieve this, providing valuable insights into the genetic regulation of steady-state RNA in human brain, but not distinguishing between molecular processes regulating transcription and stability. RNA quantification within cellular fractions can disentangle these processes in cell types and tissues which are challenging to model in vitro. We investigated the underlying molecular processes driving the genetic regulation of gene expression specific to a cellular fraction using allele-specific expression (ASE). Applying ASE analysis to genomic and transcriptomic data from paired nuclear and cytoplasmic fractions of anterior prefrontal cortex, cerebellar cortex and putamen tissues from 4 post-mortem neuropathologically-confirmed control human brains, we demonstrate that a significant proportion of genetic regulation of gene expression occurs post-transcriptionally in the cytoplasm, with genes undergoing this form of regulation more likely to be synaptic. These findings have implications for understanding the structure of gene expression regulation in human brain, and importantly the interpretation of rapidly growing single-nucleus brain RNA-sequencing and eQTL datasets, where cytoplasm-specific regulatory events could be missed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-28T15:20:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006381","title":"HSP90 inhibitor resistant cell line","description":"Genetic analysis of K562 cell which are resistant against HSP90 inhibitors.","abstract":"Genetic analysis of K562 cell which are resistant against HSP90 inhibitors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-28T15:33:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006382","title":"Single-cell study of 14 childhood medulloblastoma patients","description":null,"abstract":"Medulloblastoma intra-tumoural genetic heterogeneity and clonal evolution, and their role in disease pathogenesis and clinical behaviour, are poorly understood. We used single-cell whole-genome sequencing (sc-WGS) to reconstruct the natural history and temporal evolution of 14 medulloblastomas, representing its major clinico-molecular sub-classes. We identified wholly-clonal tumours which displayed single-clone expansion (i.e. linear evolution); all were observed in favourable-outcome sub-classes (i.e. MBWNT and infant MBSHH). In contrast, remaining tumours harboured sub-clonal structures which displayed punctuated or gradual trajectories; highest-risk sub-classes, typically characterised by MYC-amplification (MBGroup3) or TP53-mutation (MBSHH), and linked to genomic instability and LCA pathology, were most clonally-diverse. Clinically-adopted biomarkers were typically early-clonal/initiating events, representing exploitable targets for early-disease detection; in analyses of spatially-distinct tumour regions, a single biopsy was sufficient to assess their status.  sc-WGS revealed events not previously appreciated in bulk tumour analysis, which arose later and/or sub-clonally and more commonly displayed spatial diversity; their clinical significance and role in disease evolution post-diagnosis now require establishment. In summary, our findings reveal diverse modes of tumour initiation and clonal evolution in the major medulloblastoma sub-classes, highlighting their pathogenic relevance and clinical potential.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006383","title":"Exome & MiSeq sequencing of individuals with Huntington's disease","description":"The age at onset of motor symptoms in Huntington's disease (HD) is driven by HTT CAG repeat length but modified by other genes. In this study, we used exome sequencing of 683 patients with HD with extremes of onset or phenotype relative to CAG length to identify rare variants associated with clinical effect. We discovered damaging coding variants in candidate modifier genes identified in previous genome-wide association studies associated with altered HD onset or severity. Variants in FAN1 clustered in its DNA-binding and nuclease domains and were associated predominantly with earlier-onset HD. Nuclease activities of purified variants in vitro correlated with residual age at motor onset of HD. Mutating endogenous FAN1 to a nuclease-inactive form in an induced pluripotent stem cell model of HD led to rates of CAG expansion similar to those observed with complete FAN1 knockout. Together, these data implicate FAN1 nuclease activity in slowing somatic repeat expansion and hence onset of HD.","abstract":"The age at onset of motor symptoms in Huntington's disease (HD) is driven by HTT CAG repeat length but modified by other genes. In this study, we used exome sequencing of 683 patients with HD with extremes of onset or phenotype relative to CAG length to identify rare variants associated with clinical effect. We discovered damaging coding variants in candidate modifier genes identified in previous genome-wide association studies associated with altered HD onset or severity. Variants in FAN1 clustered in its DNA-binding and nuclease domains and were associated predominantly with earlier-onset HD. Nuclease activities of purified variants in vitro correlated with residual age at motor onset of HD. Mutating endogenous FAN1 to a nuclease-inactive form in an induced pluripotent stem cell model of HD led to rates of CAG expansion similar to those observed with complete FAN1 knockout. Together, these data implicate FAN1 nuclease activity in slowing somatic repeat expansion and hence onset of HD.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-28T20:59:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006384","title":"Identifying unique response and resistance mechanisms of targeted BET degradation","description":null,"abstract":"Targeted protein degradation is a transformative drug discovery strategy that employs bifunctional compounds to repurpose endogenous ubiquitin ligases to direct proteasomal degradation of targeted proteins. However, it is unknown whether target removal is the single most important cellular effect contributing to therapeutic outcome following degrader treatments. In the manuscript accompanied with this dataset, we find that proteolytic products generated by the proteasome play an active role in inducing cell death. Utilizing well-characterized BET family degraders, we show that induced degradation of the BRD4 long isoform (BRD4-L) exposes neo-amino termini that achieve a gain-of-function mechanism. Importantly, in BET degrader-resistant cells, resistance to the effects of gain-of-function peptides underlies the disconnect between largely unaltered BRD4 degradation and muted caspase activation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006385","title":"CNV profile in HSP90 inhibitor resistant K562 cells","description":"Analysis of the acquired copy number profile in K562 cell which got resistant against HSP90 inhibitors.","abstract":"Analysis of the acquired copy number profile in K562 cell which got resistant against HSP90 inhibitors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-29T15:32:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006386","title":"H3Africa - African Collaborative Center for Microbiome and Genomics Research","description":"The African Collaborative Center for Microbiome and Genomics Research is a multi-institutional collaborative research project. The objectives of the project are to collaborate and implement high impact integrative epidemiology and genomics research into discovery of biomarkers associated with cervical carcinogenesis. Specifically ACCME links and leverages existing funded research and program activities at the collaborating institutions to study the interaction between vaginal microbiome, host genetic factors and molecular variants of Human Papilloma Virus (HPV) to determine correlates of viral persistence in the causal pathway of cervical cancer, a major cause of preventable mortality in Nigeria and other parts of sub-Saharan Africa. This research offers several opportunities to advance understanding of cervical carcinogenesis, viral oncogenesis, new biomarker discovery and risk stratification by genotype in a cohort of African women.\n\nThe datasets are found here\nhttps://www.ncbi.nlm.nih.gov/bioproject/254017","abstract":"The African Collaborative Center for Microbiome and Genomics Research is a multi-institutional collaborative research project. The objectives of the project are to collaborate and implement high impact integrative epidemiology and genomics research into discovery of biomarkers associated with cervical carcinogenesis. Specifically ACCME links and leverages existing funded research and program activities at the collaborating institutions to study the interaction between vaginal microbiome, host genetic factors and molecular variants of Human Papilloma Virus (HPV) to determine correlates of viral persistence in the causal pathway of cervical cancer, a major cause of preventable mortality in Nigeria and other parts of sub-Saharan Africa. This research offers several opportunities to advance understanding of cervical carcinogenesis, viral oncogenesis, new biomarker discovery and risk stratification by genotype in a cohort of African women.\n\nThe datasets are found here\nhttps://www.ncbi.nlm.nih.gov/bioproject/254017","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006387","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__bladder","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, head and neck, bladder, gall bladder, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, head and neck, bladder, gall bladder, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006388","title":"Detection and genomic analysis of BRAF fusions in Juvenile Pilocytic Astrocytoma through the combination and integration of multi-omic data","description":"Juvenile Pilocytic Astrocytoma (JPAs) are highly vascular tumors and show pervasive immune infiltration, which can lead to low tumor cell purity in clinical samples. In some instances, this results in gene fusions that are difficult to detect with conventional omics approaches including RNA-Seq. To this effect, we applied RNA-Seq as well as linked-read whole-genome sequencing and in situ Hi-C as new approaches to detect and characterize low-frequency gene fusions at the genomic, transcriptomic and spatial level. Overall, we demonstrate the power of integrating multi-omic datasets to identify low frequency fusions and characterize the JPA genome at high resolution.","abstract":"Juvenile Pilocytic Astrocytoma (JPAs) are highly vascular tumors and show pervasive immune infiltration, which can lead to low tumor cell purity in clinical samples. In some instances, this results in gene fusions that are difficult to detect with conventional omics approaches including RNA-Seq. To this effect, we applied RNA-Seq as well as linked-read whole-genome sequencing and in situ Hi-C as new approaches to detect and characterize low-frequency gene fusions at the genomic, transcriptomic and spatial level. Overall, we demonstrate the power of integrating multi-omic datasets to identify low frequency fusions and characterize the JPA genome at high resolution.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-06-30T15:24:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006389","title":"Unraveling the genetics of transformed splenic marginal zone lymphoma","description":null,"abstract":"Whole-genome sequencing, NGS and CNA arrays of splenic marginal zone lymphomas at diagnosis and transformation","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006390","title":"HAPIEE Cohort (Siberian branch) blood DNA methylation data (Illumina EPIC arrays)","description":null,"abstract":"The HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe) study is a prospective cohort study designed to investigate the effect of classical and non-conventional risk factors and social and psychosocial factors on cardiovascular and other non-communicable diseases in eastern Europe and the FSU.\nBaseline data collection in the HAPIEE study was conducted using a comprehensive questionnaire, medical examination and the collection of venous blood samples. The protocol included assessment of history of cardiovascular and other chronic diseases, lifestyle habits and health, socio-economic circumstances, objective measurement of blood pressure (BP), anthropometric parameters and physical performance.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006391","title":"TULIPs in PFA (ChIP-Seq support)","description":null,"abstract":"ChIP-seq for H3K9me3 and H3K27me3 on PFA samples","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006392","title":"Single-cell study of 14 childhood medulloblastoma patients","description":null,"abstract":"Medulloblastoma intra-tumoural genetic heterogeneity and clonal evolution, and their role in disease pathogenesis and clinical behaviour, are poorly understood. We used single-cell whole-genome sequencing (sc-WGS) to reconstruct the natural history and temporal evolution of 14 medulloblastomas, representing its major clinico-molecular sub-classes. We identified wholly-clonal tumours which displayed single-clone expansion (i.e. linear evolution); all were observed in favourable-outcome sub-classes (i.e. MBWNT and infant MBSHH). In contrast, remaining tumours harboured sub-clonal structures which displayed punctuated or gradual trajectories; highest-risk sub-classes, typically characterised by MYC-amplification (MBGroup3) or TP53-mutation (MBSHH), and linked to genomic instability and LCA pathology, were most clonally-diverse. Clinically-adopted biomarkers were typically early-clonal/initiating events, representing exploitable targets for early-disease detection; in analyses of spatially-distinct tumour regions, a single biopsy was sufficient to assess their status.  sc-WGS revealed events not previously appreciated in bulk tumour analysis, which arose later and/or sub-clonally and more commonly displayed spatial diversity; their clinical significance and role in disease evolution post-diagnosis now require establishment. In summary, our findings reveal diverse modes of tumour initiation and clonal evolution in the major medulloblastoma sub-classes, highlighting their pathogenic relevance and clinical potential.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-01T10:26:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006393","title":"Homologous recombination deficiency derived from whole-genome sequencing predicts platinum response in triple-negative breast cancers","description":"To identify predictive biomarkers of response and resistance to platinum agents in PDX models of triple-negative breast cancer","abstract":"To identify predictive biomarkers of response and resistance to platinum agents in PDX models of triple-negative breast cancer","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-01T11:17:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006394","title":"Chromatin accessibility changes in hiPSC-derived neurons after BDNF and KCl stimulations","description":"Brain-Derived Neurotrophic Factor (BDNF) is crucial for neuronal survival, differentiation, synaptic plasticity, memory formation, and neurocognitive health. Molecular mechanisms of BDNF promoting cellular survival and synaptic plasticity have been intensely studied, yet its role in genome regulation is obscure. Using human induced pluripotent stem cell (hiPSC)-derived neurons via lentiviral delivery of the neuronal transcription factor Ngn2, we performed a temporal profiling (1h, 6h and 10h) of chromatin accessibility upon BDNF treatment or depolarization (KCl) to identify BDNF-specific chromatin-to-gene expression programs.","abstract":"Brain-Derived Neurotrophic Factor (BDNF) is crucial for neuronal survival, differentiation, synaptic plasticity, memory formation, and neurocognitive health. Molecular mechanisms of BDNF promoting cellular survival and synaptic plasticity have been intensely studied, yet its role in genome regulation is obscure. Using human induced pluripotent stem cell (hiPSC)-derived neurons via lentiviral delivery of the neuronal transcription factor Ngn2, we performed a temporal profiling (1h, 6h and 10h) of chromatin accessibility upon BDNF treatment or depolarization (KCl) to identify BDNF-specific chromatin-to-gene expression programs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-01T13:04:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006395","title":"Quantitative Exploratory Proteomics Analysis of Glioblastoma in Initial and Recurrent Tumors","description":null,"abstract":"Glioblastoma samples from 11 patients were obtained at initial and recurrent tumor stages. Proteins were extracted, identified and quantified via tandem mass spectrometry based on a TMT isobaric labelling approach. Quatitative proteomics reveals 146 differentially abundant proteins using a patient-matched statistical modelling. Analysis of proteolytic processing reveals differential proteolytic patterns in recurrent tumors. Proteogenomics reveals the presense of 30 single-amino acid variants present in glioblastoma tumor and 1 of those as increased in recurrent tumor.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-01T13:41:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006396","title":"CD8+ Tumor-Infiltrating Lymphocyte Abundance is a Positive Prognostic Indicator in Nasopharyngeal Cancer","description":"This retrospective tissue study explores the prognostic significance of tumour-infiltrating lymphocyte (TIL) populations in NPC, using a combination of RNA sequencing and immunohistochemistry.","abstract":"This retrospective tissue study explores the prognostic significance of tumour-infiltrating lymphocyte (TIL) populations in NPC, using a combination of RNA sequencing and immunohistochemistry.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-04T04:45:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006397","title":"Combined targeting of BRD4-associated Promoter Activation and NFKB Immunomodulation in ARID1A-mutated Gastric Adenocarcinoma","description":"Gastric cancer (GC) a leading causes of cancer-related deaths worldwide, with ARID1A identified as the second most frequently mutated driver gene in GC. This study involves comprehensive genomic profiling of a Singaporean cohort of over 200 GC patients to characterize the mutational signatures associated with ARID1A inactivation across various molecular subtypes of GC. The findings highlight a potential therapeutic approach for ARID1A-mutated GCs, targeting both tumor-intrinsic mechanisms (BRD4-associated promoter activation) and extrinsic immunomodulatory pathways (NFKB signaling).","abstract":"Gastric cancer (GC) a leading causes of cancer-related deaths worldwide, with ARID1A identified as the second most frequently mutated driver gene in GC. This study involves comprehensive genomic profiling of a Singaporean cohort of over 200 GC patients to characterize the mutational signatures associated with ARID1A inactivation across various molecular subtypes of GC. The findings highlight a potential therapeutic approach for ARID1A-mutated GCs, targeting both tumor-intrinsic mechanisms (BRD4-associated promoter activation) and extrinsic immunomodulatory pathways (NFKB signaling).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-04T09:33:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006398","title":"Multi-omics analyses of airway host-microbe interactions in chronic obstructive pulmonary disease identify potential therapeutic interventions","description":"The mechanistic role of the airway microbiome in chronic obstructive pulmonary disease (COPD) remains largely unexplored. We present a landscape of airway microbe-host interactions in COPD through an in-depth profiling of the sputum metagenome, metabolome, host transcriptome and proteome from 99 COPD patients and 36 healthy individuals in China.","abstract":"The mechanistic role of the airway microbiome in chronic obstructive pulmonary disease (COPD) remains largely unexplored. We present a landscape of airway microbe-host interactions in COPD through an in-depth profiling of the sputum metagenome, metabolome, host transcriptome and proteome from 99 COPD patients and 36 healthy individuals in China.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-04T15:12:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006399","title":"HSP90 inhibitor resistant cell lines","description":null,"abstract":"Genetic analysis of resistance mechanisms against HSP90 inhibitors in K562 cell line.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006400","title":"Molecular profiling of EBV associated diffuse large B-cell lymphoma","description":"We describe distinct molecular mechanisms leading to recurrent activation of JAK-STAT signaling, perturbation of epigenetic regulators as well as other direct targetable alterations such as PD-L1 amplification and overexpression contributing to immune evasion of lymphoma cells. Using the LymphGen 2.0 classifier, we combine data of recurrent mutations, somatic copy number alterations, and structural variants in an integrative analysis . For the first time, we reveal that less than 20% of primary EBV+ DLBCLs can be attributed to established molecular clusters of DLBCL NOS emphasizing the unique molecular character of this disease.","abstract":"We describe distinct molecular mechanisms leading to recurrent activation of JAK-STAT signaling, perturbation of epigenetic regulators as well as other direct targetable alterations such as PD-L1 amplification and overexpression contributing to immune evasion of lymphoma cells. Using the LymphGen 2.0 classifier, we combine data of recurrent mutations, somatic copy number alterations, and structural variants in an integrative analysis . For the first time, we reveal that less than 20% of primary EBV+ DLBCLs can be attributed to established molecular clusters of DLBCL NOS emphasizing the unique molecular character of this disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-05T12:33:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006401","title":"Study of the microenvironment of angioimmunoblastic T-cell lymphoma","description":null,"abstract":"Angioimmunoblastic T-cell lymphoma (AITL) is proposed to be initiated by age-related clonal hematopoiesis (ACH) with TET2 mutations, whereas the G17V RHOA mutation in immature cells with TET2 mutations promotes development of T follicular helper-like tumor cells. We investigated the mechanism by which TET2-mutant immune cells enable AITL development. Single-cell RNA-sequencing of human AITL samples revealed significant expansion of aberrant B cells. The genes expressed in aberrantly expanded GCB cells in murine tumors were also broadly expressed in the B-lineage cells of TET2-mutant human AITL.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-06T03:10:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006402","title":"Proteogenomics reveals two distinct biological pilocytic astrocytoma subgroups","description":"Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and driven by aberrant MAPK signaling, typically mediated by BRAF alterations. While five-year overall survival rates exceed 95%, tumor recurrence constitutes a major clinical challenge in incompletely resected tumors despite chemotherapeutic or radiation based therapies. Therefore, we used proteogenomics to discern the biological heterogeneity of PA to improve classification of this tumor entity and identify novel therapeutic targets. \n\nOur proteogenomics approach integrates RNA sequencing and LC/MS-based proteomic profiling data from a cohort of 58 confirmed, primary PA samples. An integrative genomics approach was conducted to discern the biological heterogeneity of PA and to identify aberrant pathway activation in these biological subgroups. \n\nIn summary, Pilocytic astrocytomas segregate into two groups where younger patients are significantly associated with Group 1. Importantly, we validate the two distinct biological subgroups in two non-overlapping cohorts. The biological heterogeneity seen here may improve biological classification and reveal novel therapeutic targets specifically useful for non-resectable tumors with high risk of recurrent or progressive disease.","abstract":"Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and driven by aberrant MAPK signaling, typically mediated by BRAF alterations. While five-year overall survival rates exceed 95%, tumor recurrence constitutes a major clinical challenge in incompletely resected tumors despite chemotherapeutic or radiation based therapies. Therefore, we used proteogenomics to discern the biological heterogeneity of PA to improve classification of this tumor entity and identify novel therapeutic targets. \n\nOur proteogenomics approach integrates RNA sequencing and LC/MS-based proteomic profiling data from a cohort of 58 confirmed, primary PA samples. An integrative genomics approach was conducted to discern the biological heterogeneity of PA and to identify aberrant pathway activation in these biological subgroups. \n\nIn summary, Pilocytic astrocytomas segregate into two groups where younger patients are significantly associated with Group 1. Importantly, we validate the two distinct biological subgroups in two non-overlapping cohorts. The biological heterogeneity seen here may improve biological classification and reveal novel therapeutic targets specifically useful for non-resectable tumors with high risk of recurrent or progressive disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-06T12:29:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006403","title":"Genome-wide association studies of colorectal cancer risk","description":null,"abstract":"Cases of colorectal cancer and controls have been genotyped using a variety of Illumina genotyping arrays. Some of the studies used additional controls from other datasets from Scotland - the Lothian Birth Cohorts (https://www.ed.ac.uk/lothian-birth-cohorts/data-access-collaboration) and Generation Scotland (https://www.ed.ac.uk/generation-scotland/for-researchers/access). Separate access should be sought for these datasets.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006404","title":"Sex chromosome aneuploidies give rise to changes in the circular RNA profile","description":"Purpose\nThe landscape of circular RNAs (circRNAs), an important class of non-coding RNAs that regulate gene expression, has never been described in human disorders of sex chromosome aneuploidies. We profiled circRNAs in Turner syndrome females (45,X;TS) and Klinefelter syndrome males (47,XXY; KS) to investigate how circRNAs respond to a missing or an extra X chromosome. \nMethods\nSamples of blood, muscle and fat were collected from individuals with TS (n = 33) and KS (n = 22) and from male (n = 16) and female (n = 44) controls. CircRNAs were identified using a combination of circRNA identification pipelines (CIRI2, CIRCexplorer2 and circRNA_finder). \nResults\nDifferential expression of circRNAs was observed throughout the genome in TS and KS, in all tissues. The host-genes from which several of these circRNAs were derived, were associated with known phenotypic traits. Furthermore, several differentially expressed circRNAs had the potential to capture micro RNAs that targeted protein-coding genes with altered expression in TS and KS. \nConclusion\nSex chromosome aneuploidies introduce pervasive changes in the circRNA transcriptome, demonstrating that the genomic changes in these syndromes are more complex than hitherto thought. CircRNAs may help explain some of the genomic and phenotypic traits observed in these syndromes.","abstract":"Purpose\nThe landscape of circular RNAs (circRNAs), an important class of non-coding RNAs that regulate gene expression, has never been described in human disorders of sex chromosome aneuploidies. We profiled circRNAs in Turner syndrome females (45,X;TS) and Klinefelter syndrome males (47,XXY; KS) to investigate how circRNAs respond to a missing or an extra X chromosome. \nMethods\nSamples of blood, muscle and fat were collected from individuals with TS (n = 33) and KS (n = 22) and from male (n = 16) and female (n = 44) controls. CircRNAs were identified using a combination of circRNA identification pipelines (CIRI2, CIRCexplorer2 and circRNA_finder). \nResults\nDifferential expression of circRNAs was observed throughout the genome in TS and KS, in all tissues. The host-genes from which several of these circRNAs were derived, were associated with known phenotypic traits. Furthermore, several differentially expressed circRNAs had the potential to capture micro RNAs that targeted protein-coding genes with altered expression in TS and KS. \nConclusion\nSex chromosome aneuploidies introduce pervasive changes in the circRNA transcriptome, demonstrating that the genomic changes in these syndromes are more complex than hitherto thought. CircRNAs may help explain some of the genomic and phenotypic traits observed in these syndromes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-07T12:58:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006405","title":"Somatic_mutation_in_edited_cholangiocyte_organoids_NanoSeq","description":"Characterisation of mutation rates and patterns in edited human cholangiocyte organoids (NanoSeq)","abstract":"Characterisation of mutation rates and patterns in edited human cholangiocyte organoids (NanoSeq)","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-07T14:57:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006406","title":"DNA methylation-based prognostic subtypes of chordoma tumors in tissue","description":"Chordomas are rare malignant bone cancers of the skull-base and spine. Patient survival is variable and not reliably predicted using clinical factors or molecular features. This study identifies prognostic epigenetic\nchordoma subtypes that are detected noninvasively using plasma methylomes.\nMethylation profiles of 68 chordoma surgical samples were obtained between 1996 and 2018 across three international centers along with matched plasma methylomes where available.\nConsensus clustering identified two stable tissue clusters with a disease-specific survival difference that was independent of clinical factors in a multivariate Cox analysis (HR = 14.2, 95%CI: 2.1–94.8, P = 0.0063). Immune-related pathways with genes hypomethylated at promoters and increased immune cell abundance were observed in the poorperforming “Immune-infiltrated” subtype. Cell-to-cell interaction plus extracellular matrix pathway hypomethylation and higher tumor purity were observed in the better-performing “Cellular” subtype. The findings were validated in additional DNA methylation and RNA sequencing datasets as well as with immunohistochemical staining. Plasma methylomes distinguished chordomas from other clinical differential diagnoses by applying fifty chordoma-versusother binomial generalized linear models in random 20% testing sets (mean AUROC = 0.84, 95%CI: 0.52–1.00). Tissue-based and plasma-based methylation signals were highly correlated in both prognostic clusters. Additionally, leave-one-out models accurately classified all tumors into their correct cluster based on plasma methylation data.\nHere, we show the first identification of prognostic epigenetic chordoma subtypes and first use of plasma methylome based biomarkers to noninvasively diagnose and subtype chordomas. These results may transform patient management by allowing treatment aggressiveness to be balanced with patient risk according to prognosis.","abstract":"Chordomas are rare malignant bone cancers of the skull-base and spine. Patient survival is variable and not reliably predicted using clinical factors or molecular features. This study identifies prognostic epigenetic\nchordoma subtypes that are detected noninvasively using plasma methylomes.\nMethylation profiles of 68 chordoma surgical samples were obtained between 1996 and 2018 across three international centers along with matched plasma methylomes where available.\nConsensus clustering identified two stable tissue clusters with a disease-specific survival difference that was independent of clinical factors in a multivariate Cox analysis (HR = 14.2, 95%CI: 2.1–94.8, P = 0.0063). Immune-related pathways with genes hypomethylated at promoters and increased immune cell abundance were observed in the poorperforming “Immune-infiltrated” subtype. Cell-to-cell interaction plus extracellular matrix pathway hypomethylation and higher tumor purity were observed in the better-performing “Cellular” subtype. The findings were validated in additional DNA methylation and RNA sequencing datasets as well as with immunohistochemical staining. Plasma methylomes distinguished chordomas from other clinical differential diagnoses by applying fifty chordoma-versusother binomial generalized linear models in random 20% testing sets (mean AUROC = 0.84, 95%CI: 0.52–1.00). Tissue-based and plasma-based methylation signals were highly correlated in both prognostic clusters. Additionally, leave-one-out models accurately classified all tumors into their correct cluster based on plasma methylation data.\nHere, we show the first identification of prognostic epigenetic chordoma subtypes and first use of plasma methylome based biomarkers to noninvasively diagnose and subtype chordomas. These results may transform patient management by allowing treatment aggressiveness to be balanced with patient risk according to prognosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-07T15:59:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006407","title":"Early dexamethasone therapy does not influence pulmonary fibroproliferation in COVID-19","description":null,"abstract":"Coronavirus disease 2019 (COVID-19) patients can develop pulmonary fibroproliferation (PF), which is associated with worse outcome. We investigated the influence of early dexamethasone (DEXA) treatment on the clinical course of PF, clinical fibrosis markers, and on the clinical efficacy of steroids to treat PF. Furthermore, we explored leukocytic transcriptome profiles associated with PF.\n191 critically ill COVID-19 patients spanning two treatment cohorts were included: the pre-DEXA (n=67) and the DEXA cohort (n=124). Effects of corticosteroid treatment on circulating fibrosis markers, ventilatory parameters, and clinical outcomes were analyzed between PF and no PF patients within both cohorts. Longitudinal transcriptome profiles of 52 pre-DEXA patients were determined using RNA sequencing.\nPF incidence was 28% and 25% in the pre-DEXA and DEXA cohort, respectively (p=0.61). Time on ventilator, length of stay in ICU (pre-DEXA: 42 [29-49] vs 18 [13-27] days, p&lt;0.001; DEXA: 42 [28-57] vs 13 [7-24] days, p&lt;0.001) and mortality (pre-DEXA: 47% vs 15%, p=0.009; DEXA: 61% vs 19%, p&lt;0.001) were higher in the PF groups compared to the no PF groups within both cohorts, but outcomes were comparable between PF patients of both cohorts. Several pathways were upregulated in PF patients compared to no PF patients, including inflammatory and coagulation pathways.\nIn patients with COVID-19 ARDS, PF is associated with upregulated coagulation, inflammation, and neutrophil extracellular trap-related pathways as well as prolonged ICU length of stay and mortality. Early dexamethasone treatment neither influences the incidence or clinical course of PF, nor clinical outcome.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006408","title":"Genomic landscape and molecularly-informed therapy in thymic carcinoma and other advanced thymic epithelial tumors (H021, HIPO)","description":"The molecular landscape of malignant thymic epithelial tumors (TET) is largely unknown. To better understand and target these clinically challenging entities, we characterize 81 patients harboring 46 thymus carcinomas (TC), 8 neuroendocrine tumors of the thymus (NET) and 27 thymomas using WGS/WES, transcriptome and methylome analysis. TC harbor different molecular alterations compared to thymoma and NET and have higher tumor mutational burden than thymomas. 14/76 TET patients show (likely) pathogenic germline alterations. Composite biomarker analysis indicates homologous repair deficiency in a subset of patients. We identify immunologically hot and cold TC. Cold TC show significantly shorter overall survival. 71/81 patients receive molecularly-informed therapy recommendations, which are applied in 28/71 cases leading to a DCR of 60% and an ORR of 24% (both n=25). 8/23 patients reach PFS ratios &gt; 1.3, seven of them having TC.","abstract":"The molecular landscape of malignant thymic epithelial tumors (TET) is largely unknown. To better understand and target these clinically challenging entities, we characterize 81 patients harboring 46 thymus carcinomas (TC), 8 neuroendocrine tumors of the thymus (NET) and 27 thymomas using WGS/WES, transcriptome and methylome analysis. TC harbor different molecular alterations compared to thymoma and NET and have higher tumor mutational burden than thymomas. 14/76 TET patients show (likely) pathogenic germline alterations. Composite biomarker analysis indicates homologous repair deficiency in a subset of patients. We identify immunologically hot and cold TC. Cold TC show significantly shorter overall survival. 71/81 patients receive molecularly-informed therapy recommendations, which are applied in 28/71 cases leading to a DCR of 60% and an ORR of 24% (both n=25). 8/23 patients reach PFS ratios &gt; 1.3, seven of them having TC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-08T08:23:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006409","title":"miRNA profiling of kidney transplant recipients and the risk of cytomegalovirus infection","description":null,"abstract":"In this study we aimed to determine if there was a particular miRNA profile between kidney transplant recipients with late cytomegalovirus (CMV) infection versus kidney transplant recipients not developing late CMV infection. We extracted miRNAs from whole blood specimens from 12 patients and obtained a miRNA profile by miRnome sequencing.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006410","title":"RNA sequencing data of 142 samples from 142 patients with HER2+ breast cancer treated with letrozole or tamoxifen (SOLTI PAMELA trial)","description":"PAMELA (NCT01973660) is a non-randomized, open-label, multicentric, prospective translational research study in stage I-IIIA HER2+ breast cancer designed to evaluate the ability of the PAM50 intrinsic subtypes to predict pCR in the breast (pCRB) following 18 weeks of neoadjuvant lapatinib and trastuzumab (+/- hormonal therapy if hormone receptor [HR] positive). Patients with HR+ disease received letrozole (if postmenopausal) or tamoxifen (if pre-menopausal). The primary objective was to compare the pCRB rates of the HER2-E versus the non-HER2-E subtypes in the intent-to-treat population.","abstract":"PAMELA (NCT01973660) is a non-randomized, open-label, multicentric, prospective translational research study in stage I-IIIA HER2+ breast cancer designed to evaluate the ability of the PAM50 intrinsic subtypes to predict pCR in the breast (pCRB) following 18 weeks of neoadjuvant lapatinib and trastuzumab (+/- hormonal therapy if hormone receptor [HR] positive). Patients with HR+ disease received letrozole (if postmenopausal) or tamoxifen (if pre-menopausal). The primary objective was to compare the pCRB rates of the HER2-E versus the non-HER2-E subtypes in the intent-to-treat population.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-08T12:30:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006411","title":"Induction Failure in Childhood and Young Adult T-cell Acute Lymphoblastic Leukemia","description":null,"abstract":"We carried out WGS and RNAseq on a cohort of 48 children and young adults with induction failure in T-cell Acute Lymphoblastic Leukemia (T-ALL) to identify genomic drivers of treatment resistance. The study includes WGS for 33 tumour/normal pairs and 15 tumour-only samples. In addition, there is RNAseq data for 37 cases.","study_type":"Cancer Genomics","pubmed_ids":[37098241],"external_links":null,"is_released":true,"released_date":"2022-07-08T16:13:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006412","title":"Brain_Disease_Wellcome_Leap_Delta_Mouse_Tissue_DNA","description":"Investigating how the tumour microenvironment regulates glioblastoma cell states using genomic analysis_mouse data.","abstract":"Complimentary to the human brain Leap Delta studies (which investigaties how the tumour microenvironment regulates glioblastoma cell states) this study aims to optimise new and existing DNA protocols using mouse tissue prior to use in human samples.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006413","title":"Brain_Disease_Wellcome_Leap_Delta_Mouse_Tissue_RNA","description":"Utilising Single-Nucleus sequencing to investigate how the tumour microenvironment regulates glioblastoma cell states_mouse data","abstract":"Complimentary to the human brain Leap Delta studies (which investigaties how the tumour microenvironment regulates glioblastoma cell states) this study aims to optimise new and existing RNA protocols using mouse tissue prior to use in human samples.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006414","title":"Brain_Disease_Wellcome_Leap_Delta_Mouse_Tissue_spatial","description":"Utilising spatial methods to investigate how the tumour microenvironment regulates glioblastoma cell states_mouse data","abstract":"Complimentary to the human brain Leap Delta studies (which investigaties how the tumour microenvironment regulates glioblastoma cell states) this study aims to optimise new and existing spatial protocols using mouse tissue prior to use in human samples.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006415","title":"Transcriptome profiling of GCTB cell lines","description":null,"abstract":"Transcriptome profiling of three established giant cell tumour of bone (GCTB) cell lines. Cell lines consist of neoplastic \"stromal\" cells harboring a heterozygous H3F3A p.G34W mutation. Data was used in a study (Venneker et al., 2022) to determine H3F3A-WT/MT expression ratios, to identify pathogenic variants, and to examine the expression levels of epigenetic modifiers and regulators.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006416","title":"Test","description":null,"abstract":"TBA\nTBA2\nTBA3\nNovel test\nThis is the final test. Edit on the submit. Second edit","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006417","title":"INDIA","description":"We collected PBMCs from 10 Indian and 10 Dutch individuals before BCG vaccination and 10-12 post-vaccination. We assessed the open chromatin profiles under baseline conditions, and the transcriptomic profiles upon stimulation with Influenza and SARS-CoV-2.","abstract":"We collected PBMCs from 10 Indian and 10 Dutch individuals before BCG vaccination and 10-12 post-vaccination. We assessed the open chromatin profiles under baseline conditions, and the transcriptomic profiles upon stimulation with Influenza and SARS-CoV-2.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-11T15:46:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006418","title":"Identifying cancer patients from GC-patterned fragment ends of cell-free DNA","description":"One of the most intriguing characteristics of cell-free DNA (cfDNA) from plasma is the sequence at the ends of the fragments.  Several previous studies have shown that these end-sequences are somewhat different in cancer patients than in healthy individuals.  While investigating this characteristic, we noticed that the bases at the 5’-ends of a double-stranded fragment were highly correlated with the GC content of that particular fragment. This led us to develop a method, called MendSeqS (Modified End-based sequencing System), that incorporates the correlation between end-motifs and GC content into the analysis of shallow whole genome sequencing (WGS) data. MendSeqS was able to classify patients with a sensitivity of 92-94% at a specificity of 95% in cohorts comprised of a total of 236 patients with cancer and 272 without cancer. MendSeqS could in principle be combined with other methods of cfDNA analysis to enhance cancer detection.","abstract":"One of the most intriguing characteristics of cell-free DNA (cfDNA) from plasma is the sequence at the ends of the fragments.  Several previous studies have shown that these end-sequences are somewhat different in cancer patients than in healthy individuals.  While investigating this characteristic, we noticed that the bases at the 5’-ends of a double-stranded fragment were highly correlated with the GC content of that particular fragment. This led us to develop a method, called MendSeqS (Modified End-based sequencing System), that incorporates the correlation between end-motifs and GC content into the analysis of shallow whole genome sequencing (WGS) data. MendSeqS was able to classify patients with a sensitivity of 92-94% at a specificity of 95% in cohorts comprised of a total of 236 patients with cancer and 272 without cancer. MendSeqS could in principle be combined with other methods of cfDNA analysis to enhance cancer detection.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006419","title":"Repurposing azacitidine and carboplatin to prime immune checkpoint blockade-resistant melanoma for anti-PD-L1 re-challenge","description":"Purpose: Drug repurposing offers the opportunity for chemotherapy to be used to re-establish sensitivity to immune checkpoint blockade (ICB) therapy. Here we investigated the clinical and translational aspects of an early phase II study of azacitidine and carboplatin priming for anti-PDL1 immunotherapy (Avelumab) in patients with advanced ICB-resistant melanoma.\nExperimental Design: 20 participants with ICB resistant metastatic melanoma received 2 x 4-week cycles of azacitidine and carboplatin followed by ICB re-challenge with anti-PD-L1 avelumab. The primary objective was overall response rate after priming and ICB re-challenge. Secondary objectives were Clinical benefit rate (CBR), progression-free survival (PFS) and overall survival (OS). Translational correlation analysis of HLA-A and PD-L1 expression, RNA-seq and reduced representation bisulfite sequencing (RRBS) of biopsies at baseline, after priming and after 6 cycles of avelmuab was performed. \nResults: The ORR determined after azacitidine and carboplatin priming was 10% (2/20) with 2 partial responses (PR). The ORR determined after priming followed by 6 cycles of avelumab (week 22) was 10%, with 2/20 participants achieving iPR. The CBR for azacitidine and carboplatin priming was 65% (13/20) and after priming followed by 6 cycles of avelumab CBR was 35% (n = 7/20). The median PFS was 18.0 weeks (95% CI: 14.87 – 21.13 weeks) and the median OS was 47.86 weeks (95% CI: 9.67 – 86.06 weeks). Translational correlation analysis confirmed HLA-A generally increased after priming with azacitidine and carboplatin, particularly if it was absent at the start of treatment. Average methylation of CpGs across the HLA-A locus was decreased after priming and T-cells, in particular CD8+, showed the greatest increase in infiltration.\nConclusions: Priming with azacitidine and carboplatin can induce disease stabilization and re-sensitisation to ICB for metastatic melanoma.","abstract":"Purpose: Drug repurposing offers the opportunity for chemotherapy to be used to re-establish sensitivity to immune checkpoint blockade (ICB) therapy. Here we investigated the clinical and translational aspects of an early phase II study of azacitidine and carboplatin priming for anti-PDL1 immunotherapy (Avelumab) in patients with advanced ICB-resistant melanoma.\nExperimental Design: 20 participants with ICB resistant metastatic melanoma received 2 x 4-week cycles of azacitidine and carboplatin followed by ICB re-challenge with anti-PD-L1 avelumab. The primary objective was overall response rate after priming and ICB re-challenge. Secondary objectives were Clinical benefit rate (CBR), progression-free survival (PFS) and overall survival (OS). Translational correlation analysis of HLA-A and PD-L1 expression, RNA-seq and reduced representation bisulfite sequencing (RRBS) of biopsies at baseline, after priming and after 6 cycles of avelmuab was performed. \nResults: The ORR determined after azacitidine and carboplatin priming was 10% (2/20) with 2 partial responses (PR). The ORR determined after priming followed by 6 cycles of avelumab (week 22) was 10%, with 2/20 participants achieving iPR. The CBR for azacitidine and carboplatin priming was 65% (13/20) and after priming followed by 6 cycles of avelumab CBR was 35% (n = 7/20). The median PFS was 18.0 weeks (95% CI: 14.87 – 21.13 weeks) and the median OS was 47.86 weeks (95% CI: 9.67 – 86.06 weeks). Translational correlation analysis confirmed HLA-A generally increased after priming with azacitidine and carboplatin, particularly if it was absent at the start of treatment. Average methylation of CpGs across the HLA-A locus was decreased after priming and T-cells, in particular CD8+, showed the greatest increase in infiltration.\nConclusions: Priming with azacitidine and carboplatin can induce disease stabilization and re-sensitisation to ICB for metastatic melanoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-12T05:15:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006420","title":"Repurposing azacitidine and carboplatin to prime immune checkpoint blockade-resistant melanoma for anti-PD-L1 re-challenge","description":"Purpose: Drug repurposing offers the opportunity for chemotherapy to be used to re-establish sensitivity to immune checkpoint blockade (ICB) therapy. Here we investigated the clinical and translational aspects of an early phase II study of azacitidine and carboplatin priming for anti-PDL1 immunotherapy (Avelumab) in patients with advanced ICB-resistant melanoma.\nExperimental Design: 20 participants with ICB resistant metastatic melanoma received 2 x 4-week cycles of azacitidine and carboplatin followed by ICB re-challenge with anti-PD-L1 avelumab. The primary objective was overall response rate after priming and ICB re-challenge. Secondary objectives were Clinical benefit rate (CBR), progression-free survival (PFS) and overall survival (OS). Translational correlation analysis of HLA-A and PD-L1 expression, RNA-seq and reduced representation bisulfite sequencing (RRBS) of biopsies at baseline, after priming and after 6 cycles of avelmuab was performed. \nResults: The ORR determined after azacitidine and carboplatin priming was 10% (2/20) with 2 partial responses (PR). The ORR determined after priming followed by 6 cycles of avelumab (week 22) was 10%, with 2/20 participants achieving iPR. The CBR for azacitidine and carboplatin priming was 65% (13/20) and after priming followed by 6 cycles of avelumab CBR was 35% (n = 7/20). The median PFS was 18.0 weeks (95% CI: 14.87 – 21.13 weeks) and the median OS was 47.86 weeks (95% CI: 9.67 – 86.06 weeks). Translational correlation analysis confirmed HLA-A generally increased after priming with azacitidine and carboplatin, particularly if it was absent at the start of treatment. Average methylation of CpGs across the HLA-A locus was decreased after priming and T-cells, in particular CD8+, showed the greatest increase in infiltration.\nConclusions: Priming with azacitidine and carboplatin can induce disease stabilization and re-sensitisation to ICB for metastatic melanoma.","abstract":"Purpose: Drug repurposing offers the opportunity for chemotherapy to be used to re-establish sensitivity to immune checkpoint blockade (ICB) therapy. Here we investigated the clinical and translational aspects of an early phase II study of azacitidine and carboplatin priming for anti-PDL1 immunotherapy (Avelumab) in patients with advanced ICB-resistant melanoma.\nExperimental Design: 20 participants with ICB resistant metastatic melanoma received 2 x 4-week cycles of azacitidine and carboplatin followed by ICB re-challenge with anti-PD-L1 avelumab. The primary objective was overall response rate after priming and ICB re-challenge. Secondary objectives were Clinical benefit rate (CBR), progression-free survival (PFS) and overall survival (OS). Translational correlation analysis of HLA-A and PD-L1 expression, RNA-seq and reduced representation bisulfite sequencing (RRBS) of biopsies at baseline, after priming and after 6 cycles of avelmuab was performed. \nResults: The ORR determined after azacitidine and carboplatin priming was 10% (2/20) with 2 partial responses (PR). The ORR determined after priming followed by 6 cycles of avelumab (week 22) was 10%, with 2/20 participants achieving iPR. The CBR for azacitidine and carboplatin priming was 65% (13/20) and after priming followed by 6 cycles of avelumab CBR was 35% (n = 7/20). The median PFS was 18.0 weeks (95% CI: 14.87 – 21.13 weeks) and the median OS was 47.86 weeks (95% CI: 9.67 – 86.06 weeks). Translational correlation analysis confirmed HLA-A generally increased after priming with azacitidine and carboplatin, particularly if it was absent at the start of treatment. Average methylation of CpGs across the HLA-A locus was decreased after priming and T-cells, in particular CD8+, showed the greatest increase in infiltration.\nConclusions: Priming with azacitidine and carboplatin can induce disease stabilization and re-sensitisation to ICB for metastatic melanoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-12T06:25:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006421","title":"Cystic fibrosis multi-omics study","description":"Cystic fibrosis (CF) is a genetic disorder affecting approximately 1 in 2,500 people in the UK. Here, we generated a number of high-throughput sequence data sets for monocytes and neutrophils from CF patients and matched healthy volunteers (HV); including ChIP-Seq (H3K27Ac), chromatin accessibility (ATAC-Seq), and transcript/gene expression (RNA-Seq) data. Analysis of gene expression and epigenetic profiles demonstrates a robust innate immune gene expression profile that distinguishes CF and HV during periods of disease exacerbation. Upregulation of pathways responsible for the production of proinflammatory cytokines is described.","abstract":"Cystic fibrosis (CF) is a genetic disorder affecting approximately 1 in 2,500 people in the UK. Here, we generated a number of high-throughput sequence data sets for monocytes and neutrophils from CF patients and matched healthy volunteers (HV); including ChIP-Seq (H3K27Ac), chromatin accessibility (ATAC-Seq), and transcript/gene expression (RNA-Seq) data. Analysis of gene expression and epigenetic profiles demonstrates a robust innate immune gene expression profile that distinguishes CF and HV during periods of disease exacerbation. Upregulation of pathways responsible for the production of proinflammatory cytokines is described.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-12T10:02:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006422","title":"Atypical teratoid/rhabdoid tumoroids reveal subgroup-specific drug vulnerabilities","description":"Atypical teratoid/rhabdoid tumors (ATRTs) represent a rare, but aggressive pediatric brain tumor entity. They are genetically defined by mutations in SWI/SNF chromatin remodeling complex members SMARCB1 or SMARCA4. ATRTs can be subdivided in different molecular subgroups based on their epigenetic profiles. Although recent studies suggest that the different subgroups have distinct clinical features, subgroup-specific treatment regimens have not been developed thus far. This is hampered by the lack of pre-clinical in vitro models representative of the different molecular subgroups. Here, we describe the establishment of ATRT tumoroid models from the ATRT-MYC and ATRT-SHH subgroups. We demonstrate that ATRT tumoroids retain subtype-specific epigenetic and gene expression profiles. High throughput drug screens on our ATRT tumoroids revealed distinct drug sensitivities between and within ATRT subgroups. Our ATRT tumoroids represent the first pediatric brain tumor organoid model, providing representative pre-clinical models allowing for the development of subtype-specific therapies.","abstract":"Atypical teratoid/rhabdoid tumors (ATRTs) represent a rare, but aggressive pediatric brain tumor entity. They are genetically defined by mutations in SWI/SNF chromatin remodeling complex members SMARCB1 or SMARCA4. ATRTs can be subdivided in different molecular subgroups based on their epigenetic profiles. Although recent studies suggest that the different subgroups have distinct clinical features, subgroup-specific treatment regimens have not been developed thus far. This is hampered by the lack of pre-clinical in vitro models representative of the different molecular subgroups. Here, we describe the establishment of ATRT tumoroid models from the ATRT-MYC and ATRT-SHH subgroups. We demonstrate that ATRT tumoroids retain subtype-specific epigenetic and gene expression profiles. High throughput drug screens on our ATRT tumoroids revealed distinct drug sensitivities between and within ATRT subgroups. Our ATRT tumoroids represent the first pediatric brain tumor organoid model, providing representative pre-clinical models allowing for the development of subtype-specific therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-12T21:36:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006423","title":"GWAS genotype data of Japanese","description":"GWAS genotype data of the Japanese population (N=2,380) were collected at Osaka University and the affiliated medical institutes. GWAS genotyping was performed using Infinium Asian Screening Array (Illumina, USA).","abstract":"GWAS genotype data of the Japanese population (N=2,380) were collected at Osaka University and the affiliated medical institutes. GWAS genotyping was performed using Infinium Asian Screening Array (Illumina, USA).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-13T06:48:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006424","title":"Updated RNA-seq data from WCDT metastatic Castration-Resistant Prostate Cancer (mCRPC)","description":"The goal of this study is to characterize the transcriptional landscape of advanced prostate cancer","abstract":"The goal of this study is to characterize the transcriptional landscape of advanced prostate cancer","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006425","title":"Prostate cancer ancestral genomic disparity","description":"Prostate cancer is characterised by significant global disparity; mortality rates in SubSaharan Africa are double to quadruple those in Eurasia. Hypothesising unknown interplay between genetic and non-genetic factors, tumour genome profiling envisages contributing mutational processes. Through whole-genome sequencing of treatment-naïve prostate cancer from 183 ethnically/globally distinct patients (African versus European), we generate the largest cancer genomics resource for Sub-Saharan Africa. Identifying ~2 million somatic variants, Africans carried the greatest burden. We describe a new molecular taxonomy using all mutational types and ethno39 geographic identifiers, including Asian. Defined as Global Mutational Subtypes (GMS) A–D, although Africans presented within all subtypes, we found GMS-B to be ‘African-specific’ and GMS-D ‘African-predominant’, including Admixed and European Africans. Conversely, Europeans from Australia, Africa and Brazil predominated within ‘mutationally-quiet’ and ethnically/globally ‘universal’ GMS-A, while European Australians shared a higher mutational burden with Africans in GMS45 C. GMS predicts clinical outcomes; reconstructing cancer timelines suggests four evolutionary trajectories with different mutation rates (GMS-A, low 0.968/year versus D, highest 1.315/year). Our data suggest both common genetic factors across extant populations and regional environmental factors contributing to carcinogenesis, analogous to gene-environment interaction defined here as a different effect of an environmental surrounding in persons with different ancestries or vice versa. We anticipate GMS acting as a proxy to intrinsic and extrinsic mutational processes in cancers, promoting global inclusion in landmark studies.","abstract":"Prostate cancer is characterised by significant global disparity; mortality rates in SubSaharan Africa are double to quadruple those in Eurasia. Hypothesising unknown interplay between genetic and non-genetic factors, tumour genome profiling envisages contributing mutational processes. Through whole-genome sequencing of treatment-naïve prostate cancer from 183 ethnically/globally distinct patients (African versus European), we generate the largest cancer genomics resource for Sub-Saharan Africa. Identifying ~2 million somatic variants, Africans carried the greatest burden. We describe a new molecular taxonomy using all mutational types and ethno39 geographic identifiers, including Asian. Defined as Global Mutational Subtypes (GMS) A–D, although Africans presented within all subtypes, we found GMS-B to be ‘African-specific’ and GMS-D ‘African-predominant’, including Admixed and European Africans. Conversely, Europeans from Australia, Africa and Brazil predominated within ‘mutationally-quiet’ and ethnically/globally ‘universal’ GMS-A, while European Australians shared a higher mutational burden with Africans in GMS45 C. GMS predicts clinical outcomes; reconstructing cancer timelines suggests four evolutionary trajectories with different mutation rates (GMS-A, low 0.968/year versus D, highest 1.315/year). Our data suggest both common genetic factors across extant populations and regional environmental factors contributing to carcinogenesis, analogous to gene-environment interaction defined here as a different effect of an environmental surrounding in persons with different ancestries or vice versa. We anticipate GMS acting as a proxy to intrinsic and extrinsic mutational processes in cancers, promoting global inclusion in landmark studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-13T11:02:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006426","title":"FL86_Blood__Exome_","description":"Standard whole exome sequencing of sorted blood populations.","abstract":"Investigating the driver landscape in sorted blood populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006427","title":"Dataset with genome-wide array data from 64 Tunisian and 45 Moroccan individuals.","description":null,"abstract":"In this study we assess and characterize the genetic influence from trans-Saharan migrations in current-day North Africans focussing in two sides of the Maghreb: Tunisia in the east and Morocco in the west. Tunisian individuals were sampled in the city of Tunis, and Moroccan individuals were sampled in different urban areas in the country.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-13T13:21:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006428","title":"Palbociclib resistance analyses on breast cancer bone metastasis PDX","description":"Identify mecanisms of metastatic breast cancer resistance to palbociclib by RNAseq analyses.","abstract":"Identify mecanisms of metastatic breast cancer resistance to palbociclib by RNAseq analyses.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-13T13:55:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006429","title":"Analyses of IACS-010759 treatment resistance on breast cancer bone metastases","description":"Identification of biological mecanisms involved in resistance of breast cancer bone metastases to IACS treatment.","abstract":"Identification of biological mecanisms involved in resistance of breast cancer bone metastases to IACS treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-13T16:01:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006430","title":"HCA_Immune_Aging_Biology_Spatial","description":"This project aims to generate a human lymphoid tissue atlas over space (multiple sites) and time (over 7 decades of life) using high-resolution single cell multiomics and spatial genomics approaches. For that, scRNAseq and multiome will be performed on cells from the spleen, lymph nodes, bone marrow and blood of 15 donors. In addition, multiome will be performed in stroma cells isolated from spleen and lymph nodes. Lastly, spatial transcriptomics will be performed in spleen and lymph nodes to assess cell location and tissue organisation changes with age.","abstract":"The immune system aging is responsible for the defective ability to fight infections, the lower protection obtained upon vaccination, and the increased susceptibility to cancer and autoimmune diseases in older individuals. Several alterations of the immune system that occur with aging have been described as key to immunosenescence. It is the case of the degeneration of primary lymphoid organs, the alteration of T and B cell repertoire diversity, or the abnormal systemic levels of pro-inflammatory immune mediators observed in older individuals. Notably, little is known of how human secondary lymphoid organs change with age, even though most of the immune cells reside in primary and secondary organs.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006431","title":"Whole exome-sequencing of pediatric and adult H3-K27M diffuse midline glioma","description":"H3-K27M mutant difffuse midline gliomas across different age groups and anatomical locations were profiled by WES.","abstract":"H3-K27M mutant difffuse midline gliomas across different age groups and anatomical locations were profiled by WES.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-15T10:44:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006432","title":"Malignant mesothelioma EWAS on European prospective study","description":null,"abstract":"Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer mainly caused by asbestos exposure. Specific and sensitive non-invasive biomarkers may facilitate and enhance screening programs for the early detection of cancer.\nWe investigated DNA methylation (DNAm) profiles in MPM pre-diagnostic blood samples in a case–control study nested in the European Prospective Investigation into Cancer and nutrition (EPIC) cohort, aiming to characterise DNAm biomarkers associated with MPM. From the EPIC cohort, we included samples from 134 participants who developed MPM during 20 years of follow up and from 134 matched, cancer-free, controls.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-15T15:37:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006433","title":"ctDNA quantification  in Ewing sarcoma patients","description":"Background. Treatment stratification and response assessment in pediatric sarcomas has relied on imaging studies and surgical/histopathological evidence of vital tumor cells. Such studies and evidence collection processes often involve radiation and/or general anesthesia in children. Cell-free circulating tumor DNA (ctDNA) detection in blood plasma is one available method of so-called liquid biopsies that has been shown to correlate qualitatively and quantitatively to some extent with the existence of vital tumor cells in the body. Our clinical observational study focused on the utility and feasibility of ctDNA detection in pediatric Ewing sarcoma (EWS) as a marker of minimal residual disease (MRD).\nPatients and Methods. We performed whole genome sequencing to identify the exact breakpoints in tumors known to carry the EWS-FLI1 fusion gene. Patient-specific fusion breakpoints were tracked in peripheral blood plasma using digital droplet PCR (ddPCR) before, during, and after therapy in six consecutive children and young adults with EWS. Presence and levels of fusion breakpoints were correlated with clinical disease courses. The genetic changes in the tumors were defined, and inter- and intra-individual changes in the tumor DNA copy loads were observed over time.\nResults. We show that the detection of ctDNA in the peripheral blood of EWS patients i) is feasible in the clinical routine and ii) allows for the longitudinal real-time monitoring of MRD activity in children and young adults. Although changing ctDNA levels correlated well with clinical outcome within patients, between patients, a high variability was observed (inter-individually) for the six patients described here.\nConclusions. ctDNA detection by ddPCR is a highly sensitive, specific, feasible, and highly accurate method that can be applied in EWS for follow-up assessments as an additional surrogate parameter for clinical MRD monitoring and, potentially, also for treatment stratification in the near future.","abstract":"Background. Treatment stratification and response assessment in pediatric sarcomas has relied on imaging studies and surgical/histopathological evidence of vital tumor cells. Such studies and evidence collection processes often involve radiation and/or general anesthesia in children. Cell-free circulating tumor DNA (ctDNA) detection in blood plasma is one available method of so-called liquid biopsies that has been shown to correlate qualitatively and quantitatively to some extent with the existence of vital tumor cells in the body. Our clinical observational study focused on the utility and feasibility of ctDNA detection in pediatric Ewing sarcoma (EWS) as a marker of minimal residual disease (MRD).\nPatients and Methods. We performed whole genome sequencing to identify the exact breakpoints in tumors known to carry the EWS-FLI1 fusion gene. Patient-specific fusion breakpoints were tracked in peripheral blood plasma using digital droplet PCR (ddPCR) before, during, and after therapy in six consecutive children and young adults with EWS. Presence and levels of fusion breakpoints were correlated with clinical disease courses. The genetic changes in the tumors were defined, and inter- and intra-individual changes in the tumor DNA copy loads were observed over time.\nResults. We show that the detection of ctDNA in the peripheral blood of EWS patients i) is feasible in the clinical routine and ii) allows for the longitudinal real-time monitoring of MRD activity in children and young adults. Although changing ctDNA levels correlated well with clinical outcome within patients, between patients, a high variability was observed (inter-individually) for the six patients described here.\nConclusions. ctDNA detection by ddPCR is a highly sensitive, specific, feasible, and highly accurate method that can be applied in EWS for follow-up assessments as an additional surrogate parameter for clinical MRD monitoring and, potentially, also for treatment stratification in the near future.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-16T11:49:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006434","title":"Exploring germline and somatic mutagenesis in the extended family with germline pathogenic variant in POLD1","description":"This study aimed to estimate the influence of POLD1 L474P on somatic and germline mutagenesis.\nWe studied the mutation rate and spectra in germline and soma in an extended family harboring the\nPOLD1 c.1421T&amp;gt;C p.(Leu474Pro) pathogenic variant. The study includes WGS data for DNA\nextracted from blood, fibroblasts or buccal swabs from the 16 family members, from DNA obtained\nsingle-cell derived colonies obtained from immortalized fibroblasts for 8 of 16 family members and from the same single-cell derived immortalized fibroblasts after approximately 40 passages for 6 out of 8 family members. Additionaly, study includes WXS sequencing for 1 tumor FFPE sample and adjacent normal tissue from the individual from one family member.","abstract":"This study aimed to estimate the influence of POLD1 L474P on somatic and germline mutagenesis.\nWe studied the mutation rate and spectra in germline and soma in an extended family harboring the\nPOLD1 c.1421T&amp;gt;C p.(Leu474Pro) pathogenic variant. The study includes WGS data for DNA\nextracted from blood, fibroblasts or buccal swabs from the 16 family members, from DNA obtained\nsingle-cell derived colonies obtained from immortalized fibroblasts for 8 of 16 family members and from the same single-cell derived immortalized fibroblasts after approximately 40 passages for 6 out of 8 family members. Additionaly, study includes WXS sequencing for 1 tumor FFPE sample and adjacent normal tissue from the individual from one family member.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-18T10:43:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006435","title":"HCA_Bladder_Adult_Clatworthy_RNA","description":"Cell atlas of the human bladder","abstract":"RNA-Seq for bladder cells The aim of this study to assess the single cell gene expression profile in the bladder. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006436","title":"HCA_Thymus_Disease_DiGeorge_Transplant_Alex_Kreins_Wellcome_Fellowship_RNA","description":"Single cell transcriptomics study of thymic transplant biopsies","abstract":"Allogeneic thymus transplantation is the only curative therapy for complete DiGeorge Syndrome (cDGS), a rare severe primary immunodeficiency characterised by athymia. GOSH is one of only two centres worldwide to offer this treatment. Despite a lack of major histocompatibility complex (MHC)-matching between donor and host, transplanted thymus becomes repopulated by recipient bone marrow derived precursor cells and supports development of functional T-cells. The mechanisms underlying thymopoiesis in this context are poorly understood, but over time we observe reconstitution of T-cell immunity, with the ability to produce host naïve T-cells showing a broad T-cell receptor (TCR) repertoire and to generate MHC-restricted T-cell proliferative responses. Although lifesaving, the achieved immunological reconstitution is typically not complete with circulating T-cell numbers usually remaining below the age related normal ranges. Additionally, we observe persistence of donor-derived T-cells of unknown clinical significance. To gain more insight into the mechanisms by which MHC-mismatched transplanted thymus supports T-cell development with self-tolerance, as well as into the basis of suboptimal T-cell immunity, we now aim to investigate immune reconstitution after thymus transplantation in further detail by using single-cell transcriptomics, applied to thymic transplant biopsies and peripheral blood samples collected during standard post-transplant patient care. By identifying which lineages of host- derived cells repopulate the thymic tissue after transplantation, we will be able to address the role of MHC in positive and negative T-cell selection during T-cell differentiation. We will also be able to clarify the exact ontogeny of the persistent donor T-cells, as well as their possible role. Understanding the mechanisms of action of HLA-mismatched transplanted thymus will contribute to treatment optimisation. Additionally, our research provides a unique opportunity to further investigate key immunological concepts, such as tolerance and autoimmunity, challenging existing paradigms in thymus immunology.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-18T12:29:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006437","title":"HCA_Thymus_Disease_DiGeorge_Transplant_Alex_Kreins_Wellcome_Fellowship_Spatial","description":"Spatial transcriptomics study of thymic transplant biopsies","abstract":"Allogeneic thymus transplantation is the only curative therapy for complete DiGeorge Syndrome (cDGS), a rare severe primary immunodeficiency characterised by athymia. GOSH is one of only two centres worldwide to offer this treatment. Despite a lack of major histocompatibility complex (MHC)-matching between donor and host, transplanted thymus becomes repopulated by recipient bone marrow derived precursor cells and supports development of functional T-cells. The mechanisms underlying thymopoiesis in this context are poorly understood, but over time we observe reconstitution of T-cell immunity, with the ability to produce host naïve T-cells showing a broad T-cell receptor (TCR) repertoire and to generate MHC-restricted T-cell proliferative responses. Although lifesaving, the achieved immunological reconstitution is typically not complete with circulating T-cell numbers usually remaining below the age related normal ranges. Additionally, we observe persistence of donor-derived T-cells of unknown clinical significance. To gain more insight into the mechanisms by which MHC-mismatched transplanted thymus supports T-cell development with self-tolerance, as well as into the basis of suboptimal T-cell immunity, we now aim to investigate immune reconstitution after thymus transplantation in further detail by using single-cell transcriptomics, applied to thymic transplant biopsies and peripheral blood samples collected during standard post-transplant patient care. By identifying which lineages of host- derived cells repopulate the thymic tissue after transplantation, we will be able to address the role of MHC in positive and negative T-cell selection during T-cell differentiation. We will also be able to clarify the exact ontogeny of the persistent donor T-cells, as well as their possible role. Understanding the mechanisms of action of HLA-mismatched transplanted thymus will contribute to treatment optimisation. Additionally, our research provides a unique opportunity to further investigate key immunological concepts, such as tolerance and autoimmunity, challenging existing paradigms in thymus immunology.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-18T12:41:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006438","title":"Diagnostic yield of Affymentrix Optima Microarray in autism spectrum disorder in India","description":null,"abstract":"The study explores the diagnostic yield of Affymetrix Optima Microarray in patients diagnosed with non-syndromic autism spectrum disorders (according to the DSM-V criteria) in India. Patients were previously screened for aneuploidies using chromosomal G-banded karyotyping (at 500 band resolution) and Fragile-X using TP-PCR. Affymetrix Optima Microarray was performed on germline DNA from 100 idiopathic patients. This submission comprises of phenotypic characteristics along with access to raw genetic data (CEL files) under controlled access.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006439","title":"Copy Number Variation using Affymetrix Optima Array","description":"Diagnostic yield of affymetrix optima microarray in patients with non-syndromic autism spectrum disorders in India.","abstract":"Diagnostic yield of affymetrix optima microarray in patients with non-syndromic autism spectrum disorders in India.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-18T13:35:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006440","title":"Genetic regulation of RNA splicing in human pancreatic islets","description":"Genetic variants that influence transcriptional regulation in pancreatic islets play a major role in the susceptibility to type 2 diabetes (T2D). For many susceptibility loci, however, the mechanisms are unknown. To this end, we examined splicing and gene expression QTLs (sQTLs and eQTLs) in pancreatic islets from 399 human donors from publicly available cohorts and in-house data. Here we provide newly generated RNA-seq data and genotyping array data from 101 donors.","abstract":"Genetic variants that influence transcriptional regulation in pancreatic islets play a major role in the susceptibility to type 2 diabetes (T2D). For many susceptibility loci, however, the mechanisms are unknown. To this end, we examined splicing and gene expression QTLs (sQTLs and eQTLs) in pancreatic islets from 399 human donors from publicly available cohorts and in-house data. Here we provide newly generated RNA-seq data and genotyping array data from 101 donors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-18T15:07:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006441","title":"Transcriptome profiling of three giant cell tumour of bone cell lines","description":"Transcriptome profiling of three established giant cell tumour of bone (GCTB) cell lines on the BGISEQ-500 platform (PE100). Cell lines consist of neoplastic \"stromal\" cells harboring a heterozygous H3F3A p.G34W mutation. Data was used in a study (Venneker et al., Histone deacetylase inhibitors as a therapeutic strategy to eliminate neoplastic “stromal” cells from giant cell tumors of bone, 2022) to determine H3F3A-WT/MT expression ratios, to identify pathogenic variants, and to examine the expression levels of epigenetic modifiers and regulators.","abstract":"Transcriptome profiling of three established giant cell tumour of bone (GCTB) cell lines on the BGISEQ-500 platform (PE100). Cell lines consist of neoplastic \"stromal\" cells harboring a heterozygous H3F3A p.G34W mutation. Data was used in a study (Venneker et al., Histone deacetylase inhibitors as a therapeutic strategy to eliminate neoplastic “stromal” cells from giant cell tumors of bone, 2022) to determine H3F3A-WT/MT expression ratios, to identify pathogenic variants, and to examine the expression levels of epigenetic modifiers and regulators.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-19T09:56:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006442","title":"Time-dependent characterization of CNS response in COVID-19","description":"Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 primarily affects the respiratory system, but the observation of diverse neurological symptoms indicates that other organs, including the brain, may be involved. The pathophysiological mechanisms of COVID-19-associated effects on the central nervous system (CNS) have become clearer during the past two years. Nevertheless, the precise CNS-specific molecular mechanisms are still elusive and raise several questions. To further elucidate the host response at brain tissue level, we profiled single-nucleus transcriptomes and performed proteomics from olfactory mucosa, olfactory bulb, medulla oblongata and cerebellum at different timepoints of the disease in individuals who died of COVID-19 and underwent rapid autopsy.","abstract":"Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 primarily affects the respiratory system, but the observation of diverse neurological symptoms indicates that other organs, including the brain, may be involved. The pathophysiological mechanisms of COVID-19-associated effects on the central nervous system (CNS) have become clearer during the past two years. Nevertheless, the precise CNS-specific molecular mechanisms are still elusive and raise several questions. To further elucidate the host response at brain tissue level, we profiled single-nucleus transcriptomes and performed proteomics from olfactory mucosa, olfactory bulb, medulla oblongata and cerebellum at different timepoints of the disease in individuals who died of COVID-19 and underwent rapid autopsy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-19T10:12:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006443","title":"Engineered_cartilage__deriving_design_principles_from_human_developmental_pathways","description":"Engineered cartilage: deriving design principles from human developmental pathways","abstract":"Engineered cartilage: deriving design principles from human developmental pathways","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-19T12:20:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006444","title":"Airway Dysbiosis Accelerates Lung Function Decline in Chronic Obstructive Pulmonary Disease","description":"This repository contains human sample derived microbiome full-length 16S rRNA sequencing data for sputum samples in COPD patients. The project goal is to understand the association of the lung microbiome with accelerated lung function decline in COPD patients.","abstract":"This repository contains human sample derived microbiome full-length 16S rRNA sequencing data for sputum samples in COPD patients. The project goal is to understand the association of the lung microbiome with accelerated lung function decline in COPD patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-19T14:14:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006445","title":"T cell reactivity of MHC epitopes","description":"By using &gt;36,000 immunogenicity assay results, we developed a method to identify peptide-MHC complexes whose structural alignment facilitates T cell reaction. Our method accurately predicted neoepitopes for MHC II as well as MHC I that were responsive to checkpoint blockade when applied to &amp;gt;1,200 samples of various tumor types and on-therapy melanoma samples. To investigate selection by spontaneous immunity at the single epitope level, we analyzed the frequency spectrum of &amp;gt;25 million mutations in &amp;gt;9,000 treatment-naïve tumors in association with &amp;gt;100 immune phenotypes. MHC II immunogenicity specifically lowered variant frequencies in tumors under high immune pressure particularly with high TCR clonality and MHC II expression.","abstract":"By using &gt;36,000 immunogenicity assay results, we developed a method to identify peptide-MHC complexes whose structural alignment facilitates T cell reaction. Our method accurately predicted neoepitopes for MHC II as well as MHC I that were responsive to checkpoint blockade when applied to &amp;gt;1,200 samples of various tumor types and on-therapy melanoma samples. To investigate selection by spontaneous immunity at the single epitope level, we analyzed the frequency spectrum of &amp;gt;25 million mutations in &amp;gt;9,000 treatment-naïve tumors in association with &amp;gt;100 immune phenotypes. MHC II immunogenicity specifically lowered variant frequencies in tumors under high immune pressure particularly with high TCR clonality and MHC II expression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-21T04:13:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006446","title":"HCA_Brain_Foetal_SFARI_RNA","description":"Study of ASD genes in foetal brain","abstract":"Autism is a multifactorial spectrum of neurodevelopmental disorders with complex genetic traits underlying their etiology. To hypothesize whether genes implicated in the Autism Spectrum Disorder (ASD) affect the development or function of specific brain circuits, researchers often intersect ASD gene lists with transcriptomic datasets of the human cerebral cortex across development. Remarkably, some of these genes express in a regional manner across the rostro-caudal axis of the prenatal cortex, implicating spatially distinct subtypes of subplate neurons in ASD. However, we lack high-quality validation of such spatiotemporal expression patterns of ASD genes in subplate neurons and other neural types on intact human brain tissue.We hypothesize that understanding the cell type, region and age-specific expression patterns of ASD genes in the human brain represents a major step towards understanding the etiology of the disorder. Here, we seek funding to initiate an open-access resource of Spatio-Temporal Autism Gene Expression (STAGE) where we will survey intact human brain tissue using novel spatial transcriptomic methods. In this pilot proposal, we hypothesize that regional populations of human subplate neurons show ASD-linked gene expression and we propose to validate these patterns in situ in the prenatal and adult human cerebral cortex using spatial transcriptomic technologies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006447","title":"HCA_Brain_Foetal_SFARI_spatial","description":"Spatial study of ASD genes in foetal brain","abstract":"Autism is a multifactorial spectrum of neurodevelopmental disorders with complex genetic traits underlying their etiology. To hypothesize whether genes implicated in the Autism Spectrum Disorder (ASD) affect the development or function of specific brain circuits, researchers often intersect ASD gene lists with transcriptomic datasets of the human cerebral cortex across development. Remarkably, some of these genes express in a regional manner across the rostro-caudal axis of the prenatal cortex, implicating spatially distinct subtypes of subplate neurons in ASD. However, we lack high-quality validation of such spatiotemporal expression patterns of ASD genes in subplate neurons and other neural types on intact human brain tissue.We hypothesize that understanding the cell type, region and age-specific expression patterns of ASD genes in the human brain represents a major step towards understanding the etiology of the disorder. Here, we seek funding to initiate an open-access resource of Spatio-Temporal Autism Gene Expression (STAGE) where we will survey intact human brain tissue using novel spatial transcriptomic methods. In this pilot proposal, we hypothesize that regional populations of human subplate neurons show ASD-linked gene expression and we propose to validate these patterns in situ in the prenatal and adult human cerebral cortex using spatial transcriptomic technologies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006448","title":"HCA_Brain_Adult_SFARI_RNA","description":"Study of ASD genes in adult brain","abstract":"Autism is a multifactorial spectrum of neurodevelopmental disorders with complex genetic traits underlying their etiology. To hypothesize whether genes implicated in the Autism Spectrum Disorder (ASD) affect the development or function of specific brain circuits, researchers often intersect ASD gene lists with transcriptomic datasets of the human cerebral cortex across development. Remarkably, some of these genes express in a regional manner across the rostro-caudal axis of the prenatal cortex, implicating spatially distinct subtypes of subplate neurons in ASD. However, we lack high-quality validation of such spatiotemporal expression patterns of ASD genes in subplate neurons and other neural types on intact human brain tissue.We hypothesize that understanding the cell type, region and age-specific expression patterns of ASD genes in the human brain represents a major step towards understanding the etiology of the disorder. Here, we seek funding to initiate an open-access resource of Spatio-Temporal Autism Gene Expression (STAGE) where we will survey intact human brain tissue using novel spatial transcriptomic methods. In this pilot proposal, we hypothesize that regional populations of human subplate neurons show ASD-linked gene expression and we propose to validate these patterns in situ in the prenatal and adult human cerebral cortex using spatial transcriptomic technologies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006449","title":"HCA_Brain_Adult_SFARI_spatial","description":"Spatial study of ASD genes in adult brain","abstract":"Autism is a multifactorial spectrum of neurodevelopmental disorders with complex genetic traits underlying their etiology. To hypothesize whether genes implicated in the Autism Spectrum Disorder (ASD) affect the development or function of specific brain circuits, researchers often intersect ASD gene lists with transcriptomic datasets of the human cerebral cortex across development. Remarkably, some of these genes express in a regional manner across the rostro-caudal axis of the prenatal cortex, implicating spatially distinct subtypes of subplate neurons in ASD. However, we lack high-quality validation of such spatiotemporal expression patterns of ASD genes in subplate neurons and other neural types on intact human brain tissue.We hypothesize that understanding the cell type, region and age-specific expression patterns of ASD genes in the human brain represents a major step towards understanding the etiology of the disorder. Here, we seek funding to initiate an open-access resource of Spatio-Temporal Autism Gene Expression (STAGE) where we will survey intact human brain tissue using novel spatial transcriptomic methods. In this pilot proposal, we hypothesize that regional populations of human subplate neurons show ASD-linked gene expression and we propose to validate these patterns in situ in the prenatal and adult human cerebral cortex using spatial transcriptomic technologies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006450","title":"COVID_19_Bayraktar_Core_spatial","description":"Understanding the immune response to SARS-CoV-2 using spatial genomics and transcriptomics.","abstract":"Spatial transcriptomics will be performed on COVID-19 samples to gain further understanding of the the immune response to SARS-CoV-2.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006451","title":"Detection of specific alterations in brain tumor patients.","description":null,"abstract":"Malignant brain tumors present an enormous challenge due to their genetic heterogeneity and difficult access impeding a precise diagnosis. Numerous genetic alterations have been described and some of them can assist in personalized therapy of glioma patients. Brain biopsy is an invasive procedure with potential deleterious complications. Liquid biopsy from patient’s serum may provide more precise diagnostics and better selection of personalized therapy from a simple blood draw.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006452","title":"WGS of PMBCL","description":null,"abstract":"We performed whole-genome sequencing of 14 paired tumor and normal samples of primary mediastinal B-cell lymphomas. Enrichment of somatic mutations and structural variants and mutational signature were studied.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-22T02:08:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006453","title":"Whole-Exome Sequencing analyses in tamoxifen-associated endometrial cancer","description":"An increased incidence of endometrial cancer has been described for patients that have received tamoxifen to treat breast cancer. Using samples from endometrial tumors, isolated from surgivcal specimens of patients who previously received tamoxifen treatment for breast cancer, we aimed to identify whether there are specific somatic mutations enriched in this population, relative to endometrial tumors from the general population. For this, WES was performed on matched endometrial tumors and healthy tissue (n=21).","abstract":"An increased incidence of endometrial cancer has been described for patients that have received tamoxifen to treat breast cancer. Using samples from endometrial tumors, isolated from surgivcal specimens of patients who previously received tamoxifen treatment for breast cancer, we aimed to identify whether there are specific somatic mutations enriched in this population, relative to endometrial tumors from the general population. For this, WES was performed on matched endometrial tumors and healthy tissue (n=21).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-22T09:56:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006454","title":"Effect_of_platinum_on_whole_blood_NanoSeq","description":"Whole-genome NanoSeq to assess the effect of platinum chemotherapy on the mutation burden and signatures found in whole blood.","abstract":"Whole-genome NanoSeq to assess the effect of platinum chemotherapy on the mutation burden and signatures found in whole blood.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-22T13:28:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006455","title":"TP53 alterations are associated with poor survival in patients with primary mediastinal nonseminoma germ cell tumors","description":null,"abstract":"Primary mediastinal nonseminoma germ cell tumors (PMNSGCT) represent a clinically distinct subgroup of nonseminoma germ cell tumors (GCT) and are considered poor risk according to the IGCCCG classification. In this study we aimed to evaluate PMNSGCT specific genomic landscape and correlate specific somatic alterations with clinical outcomes. Archival tumor specimens were analyzed from 28 patients with mediastinal GCT (3 seminoma and 25 nonseminoma). High-density tumor areas were selected for DNA extraction and subject to targeted sequencing of 578 pan-cancer genes. Three patients (11%) were identified as karyotype XXY (Klinefelter Syndrome). We identified 16/28 (57%) tumor samples with amplification of chromosome 12p, 3/28 (11%) with amplification of chromosome X and 2/28 (7%) with deletion of chromosome Y. Somatic mutations were detected in 19/28 (68%) samples. The most frequently mutated genes were: TP53 (13/28; 46%), KIT (5/28; 18%) and KRAS (5/28; 18%). No TP53 alterations were detected in the seminoma samples. Overall, deleterious TP53 alterations were identified in 14/28 (50%) specimens and were associated with significantly reduced overall survival (HR: 7.16; p=0.012).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006456","title":"Genomic analysis and evolutionary modeling of breast and larynx cancer, based on specimens from Polish population","description":"We explore the genomic characteristics of the original dataset of breast and larynx cancer specimens of several cell types from the collection of the Department of Applied Radiology of the Maria Sklodowska-Curie National Research Institute of Oncology, Krakow (Poland) Branch and Institute of Human Genetics Polish Academy of Sciences. DNA from paired tissue samples from primary tumor locations and concurrent metastasis to regional lymph nodes was sequenced and matched to controls. A range of genomic analyses was carried out, such as estimation of variant allele frequencies (VAF) and copy number variation (CNV). They show that subsets of variants from primary tumors are present in metastatic lymph nodes and that the CNV pattern is similar, but not identical to that known in the literature. In addition to that, we fit the VAF data to theoretical site frequency spectra predicted by multiple models found in the literature. Analysis suggests existence of secondary advantageous subclones arising on the clonal background as well as of a number of neutral or slightly deleterious passenger mutations.","abstract":"We explore the genomic characteristics of the original dataset of breast and larynx cancer specimens of several cell types from the collection of the Department of Applied Radiology of the Maria Sklodowska-Curie National Research Institute of Oncology, Krakow (Poland) Branch and Institute of Human Genetics Polish Academy of Sciences. DNA from paired tissue samples from primary tumor locations and concurrent metastasis to regional lymph nodes was sequenced and matched to controls. A range of genomic analyses was carried out, such as estimation of variant allele frequencies (VAF) and copy number variation (CNV). They show that subsets of variants from primary tumors are present in metastatic lymph nodes and that the CNV pattern is similar, but not identical to that known in the literature. In addition to that, we fit the VAF data to theoretical site frequency spectra predicted by multiple models found in the literature. Analysis suggests existence of secondary advantageous subclones arising on the clonal background as well as of a number of neutral or slightly deleterious passenger mutations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-23T22:18:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006457","title":"Chromatin activation profiling of stereotyped chronic lymphocytic leukemias reveals a subset #8 specific signature","description":"The chromatin activation landscape of major subsets of chronic lymphocytic leukemia (CLL) with stereotyped B-cell receptor immunoglobulin is currently unknown. Here, we report the results of a whole-genome chromatin profiling of histone 3 lysine 27 acetylation of 18 CLLs from subsets #1, #2, #4, and #8 which were compared against non-stereotyped CLLs and normal B cell subpopulations. Although subsets #1, #2, and #4 were similar to their non-stereotyped CLL counterparts with concordant somatic hypermutation status, subset #8 displayed a remarkably different chromatin activation profile.","abstract":"The chromatin activation landscape of major subsets of chronic lymphocytic leukemia (CLL) with stereotyped B-cell receptor immunoglobulin is currently unknown. Here, we report the results of a whole-genome chromatin profiling of histone 3 lysine 27 acetylation of 18 CLLs from subsets #1, #2, #4, and #8 which were compared against non-stereotyped CLLs and normal B cell subpopulations. Although subsets #1, #2, and #4 were similar to their non-stereotyped CLL counterparts with concordant somatic hypermutation status, subset #8 displayed a remarkably different chromatin activation profile.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-25T14:46:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006458","title":"HIPSCI_TF_Multiome_seq","description":"The technology for generating cell types in-vitro and for controlling their identity remains limited due to the lack of predictive and causal models of transcriptional regulation that reliably work across 100s of cell types. To fill the gap, we are developing a tool, built from first principles, that predicts combinations of context-defining and context-dependent transcription factors (TFs) for every cell subpopulation by taking in chromatin accessibility and gene expression data from the same cell. In this project, we plan to systematically validate the model through experimental activation of 400 TF combinations in induced pluripotent stem cells and measure outcomes on both transcriptome and chromatin accessibility. For this purpose, we will express transcription factors in hIPSCs either with exogenous cDNA expression or with CRISPR-activation of endogenous genes. Following 4 days we will collect and sort cells for cDNA/gRNA expression, isolate nuclei and run 10X-Multiome (Gene Expression+ATAC) seq. we will identify effect of transcription factor activation on transcriptome and chromatin accesibility by sequencing Gene expression and ATAC libraries obtained from 10X. Additionally, to identfy dynamics of TF acitivation, we will analyse selected TF combinations in 5 different time points by 10X scRNAseq.","abstract":"The major bottleneck for in vitro translational research is the availability of disease-relevant cellular contexts. Similarly, the emerging possibility of reversing the disease states back to health using in-vivo gene therapies is constrained by tools for controlling existing cell types. The technology for generating cell types in-vitro and for controlling their identity remains limited due to the lack of predictive and causal models of transcriptional regulation that reliably work across 100s of cell types. For example, specific subtypes of inhibitory neurones are being explored as a treatment for epilepsy but are challenging to generate due to subtype-defining transcription factors (TFs) being reused in other cell types. To fill the gap, we are developing a tool, built from first principles, that predicts combinations of context-defining and context-dependent TFs for every cell subpopulation by taking in 1) chromatin accessibility and gene expression data from the same cell (multiome) and 2) DNA sequence for predicting TF binding. Crucially, the tool leverages large scale cell atlases to derive a transcriptional regulation model comprehensively representing a broad range of cell types. Here, we seek funding to systematically validate the model through experimental activation of 400 TF combinations in induced pluripotent stem cells. This experiment would establish a proof of concept derivation of 10s of previously inaccessible disease-relevant cell subtypes that can then be dissected in vitro - with the ultimate goal of creating a platform to accelerate generating and controlling novel cell types for disease modelling and therapy.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006459","title":"Case Report: early contribution of germline and nevi genetic alterations to a rapidly-progressing Cutaneous Melanoma Patient","description":null,"abstract":"Background. Cutaneous Melanoma is a skin cancer with a high mutational burden and a high metastatic rate. Early genetic alterations and biomarkers of distant progression are a point of interest. Adding to germline-susceptibility loci, almost 30% of melanomas arise from precursor benign nevi lesions, constituting a source for malignant transformation.\nCase Presentation. Patient#009 developed a primary tumor over a pre-existing nevus, followed by regional and distant metastases, deceasing 7 months after diagnosis. To search for the genetic contribution to this rapid progression, longitudinal whole-exome sequencing analysis was performed on germline, nevi, primary tumor, and a metastatic lymph node. Tumor-associated nevus was analyzed splitted into two sections, adjacent and distant to the tumor. Differential SNP/INDEL and CNV gene alterations, with functional impact on key pathways and cancer hallmarks in each step of evolution, were discerned. \nGermline-trunk SNP were detected with stable allele-frequency from germline to metastasis; mainly affecting DNA-repair genes, promoting genomic instability. Early somatic-trunk alterations, detected in nevi and persisting in primary tumor and metastasis, included BRAFV600E and focal CNV with copy loss of several genes involved in DNA repair, cytoskeleton regulation, intercellular connections, chemokines and vesicular transport, acquiring additional cancer-hallmarks. Adjacent and distant nevi were rich in alterations, presenting differential SNP and CNV alterations. \nUpon tumor transformation, a marked increase in CNV over SNP alterations were detected. Both the number of SNP and CNV-affected genes, including known driver genes, increased throughout progression, although TMB levels remained lower than expected for melanomas. Typical alterations of  BRAFV600E tumors related to intrinsic resistance to BRAF-inhibitors were detected, including BRAF amplification and loss of NF1, PTEN, CDKN2A/B and TP53 surveillance genes. Finally, numerous metastatic alterations were detected, further promoting tumor progression.\nConclusions. In this patient, a longitudinal WES analysis was performed, from germline to benign and tumor lesions, revealing a sequential and cumulative pattern of genetic alterations, where germline and nevi somatic events contributed early to its rapid clinical progression. In this case report, we found that nevi can be genetically heterogeneous entities, providing a fertile precursor for melanoma transformation and progression, in which prognostic biomarkers should be further studied.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-25T20:26:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006460","title":"RaScALL: Rapid screening of RNA-seq in acute lymphoblastic leukaemia","description":"RNA-sequencing (RNA-seq) efforts in acute lymphoblastic leukaemia (ALL) have identified numerous prognostically significant genomic alterations which can guide diagnostic risk stratification and treatment choices when detected early. However, a full RNA-seq Bioinformatics workflow is time-consuming and costly in a clinical setting where rapid detection and accurate reporting of clinically relevant alterations are essential. To accelerate the identification of ALL-specific alterations (including gene fusions, single nucleotide variants and focal gene deletions), we developed the rapid screening tool RaScALL, capable of identifying more than 100 prognostically significant lesions directly from raw sequencing reads. RaScALL uses the k-mer based targeted detection tool km and known ALL variant information to achieve a high degree of accuracy for reporting subtype defining genomic alterations compared to standard alignment-based pipelines. Gene fusions, including difficult to detect fusions involving EPOR and DUX4, were accurately identified in 98% (164 samples) of reported cases in a 180-patient Australian study cohort and 95% (n=63) of samples in a North American validation cohort. Pathogenic sequence variants were correctly identified in 75% of tested samples, including all cases involving subtype defining variants PAX5 p.P80R (n=12) and IKZF1 p.N159Y (n=4). Accurate detection of intragenic IKZF1 deletions resulting in aberrant transcript isoforms was also detectable with 98% accuracy. Importantly, the median analysis time for detection of all targeted alterations averaged 22 minutes per sample, significantly shorter than standard alignment-based approaches, ensuring accerelated risk-stratification and therapeutic triage.","abstract":"RNA-sequencing (RNA-seq) efforts in acute lymphoblastic leukaemia (ALL) have identified numerous prognostically significant genomic alterations which can guide diagnostic risk stratification and treatment choices when detected early. However, a full RNA-seq Bioinformatics workflow is time-consuming and costly in a clinical setting where rapid detection and accurate reporting of clinically relevant alterations are essential. To accelerate the identification of ALL-specific alterations (including gene fusions, single nucleotide variants and focal gene deletions), we developed the rapid screening tool RaScALL, capable of identifying more than 100 prognostically significant lesions directly from raw sequencing reads. RaScALL uses the k-mer based targeted detection tool km and known ALL variant information to achieve a high degree of accuracy for reporting subtype defining genomic alterations compared to standard alignment-based pipelines. Gene fusions, including difficult to detect fusions involving EPOR and DUX4, were accurately identified in 98% (164 samples) of reported cases in a 180-patient Australian study cohort and 95% (n=63) of samples in a North American validation cohort. Pathogenic sequence variants were correctly identified in 75% of tested samples, including all cases involving subtype defining variants PAX5 p.P80R (n=12) and IKZF1 p.N159Y (n=4). Accurate detection of intragenic IKZF1 deletions resulting in aberrant transcript isoforms was also detectable with 98% accuracy. Importantly, the median analysis time for detection of all targeted alterations averaged 22 minutes per sample, significantly shorter than standard alignment-based approaches, ensuring accerelated risk-stratification and therapeutic triage.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-26T09:08:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006461","title":"High-resolution lung adenocarcinoma expression subtypes identify tumors with dependencies on MET, CDK4, CDK6, and PD-L1","description":"Lung adenocarcinoma is one of the most common cancer types with various treatment modalities. However, better biomarkers to predict therapeutic response are still needed to improve precision medicine. We utilized a consensus hierarchical clustering approach on 509 LUAD cases from TCGA to identify five robust LUAD expression subtypes. We then integrated genomic (patient and cell line) and proteomic data to help define biomarkers of response to targeted therapies and immunotherapies. This approach defined subtypes with unique proteogenomic and dependency\nprofiles.","abstract":"Lung adenocarcinoma is one of the most common cancer types with various treatment modalities. However, better biomarkers to predict therapeutic response are still needed to improve precision medicine. We utilized a consensus hierarchical clustering approach on 509 LUAD cases from TCGA to identify five robust LUAD expression subtypes. We then integrated genomic (patient and cell line) and proteomic data to help define biomarkers of response to targeted therapies and immunotherapies. This approach defined subtypes with unique proteogenomic and dependency\nprofiles.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-26T15:25:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006462","title":"Multimodal Epigenetic Sequencing Analysis (MESA) of Cell-free DNA for Non-invasive Cancer Detection","description":"Multimodal characterization of cell-free DNA (cfDNA) in the blood can enable the sensitive and non-invasive detection of human cancers but remains technically challenging and costly. Here, we developed Multimodal Epigenetic Sequencing Analysis (MESA), a flexible and sensitive method of capturing and integrating multimodal epigenetic information of cfDNA using a single experimental assay, i.e., non-disruptive bisulfite-free methylation sequencing, such as Enzymatic Methyl-seq (EM-seq) and TET-assisted pyridine borane sequencing (TAPS). MESA can simultaneously infer cfDNA methylation, nucleosome occupancy, nucleosome fuzziness, and fragmentation profile for regions surrounding the promoters and polyadenylation sites (PASs). MESA’s integrated analysis of multimodal epigenetic features significantly improved the performance of cancer detection models compared to the usage of any single modality alone. MESA captures additional and highly complementary epigenetic information from cfDNA without additional experimental assays, highlighting the importance and clinical prospect of using multimodal epigenetic features for non-invasive cancer detection","abstract":"Multimodal characterization of cell-free DNA (cfDNA) in the blood can enable the sensitive and non-invasive detection of human cancers but remains technically challenging and costly. Here, we developed Multimodal Epigenetic Sequencing Analysis (MESA), a flexible and sensitive method of capturing and integrating multimodal epigenetic information of cfDNA using a single experimental assay, i.e., non-disruptive bisulfite-free methylation sequencing, such as Enzymatic Methyl-seq (EM-seq) and TET-assisted pyridine borane sequencing (TAPS). MESA can simultaneously infer cfDNA methylation, nucleosome occupancy, nucleosome fuzziness, and fragmentation profile for regions surrounding the promoters and polyadenylation sites (PASs). MESA’s integrated analysis of multimodal epigenetic features significantly improved the performance of cancer detection models compared to the usage of any single modality alone. MESA captures additional and highly complementary epigenetic information from cfDNA without additional experimental assays, highlighting the importance and clinical prospect of using multimodal epigenetic features for non-invasive cancer detection","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-27T08:50:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006463","title":"in silico drug target prediction for melanoma","description":"The in silico single gene deletion step was adapted to simulate the knock-out of all targets of a drug on an objective function such as growth or energy balance. Based on publicly available and in-house large scale transcriptomic data, metabolic models for melanoma were reconstructed, enabling the prediction of 28 candidate drugs and estimating their respective efficacy.","abstract":"The in silico single gene deletion step was adapted to simulate the knock-out of all targets of a drug on an objective function such as growth or energy balance. Based on publicly available and in-house large scale transcriptomic data, metabolic models for melanoma were reconstructed, enabling the prediction of 28 candidate drugs and estimating their respective efficacy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-27T11:37:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006464","title":"Colorectal cancer transcriptomics with primary and metastatic samples","description":"We performed RNAseq analysis of metastatic colorectal cancer from 16 patients. Normal adjacent tissue, primary tissue, and metastatic tissue were analyzed to uncover metastatic progression and difference between primary and distant metastatic lesions.","abstract":"We performed RNAseq analysis of metastatic colorectal cancer from 16 patients. Normal adjacent tissue, primary tissue, and metastatic tissue were analyzed to uncover metastatic progression and difference between primary and distant metastatic lesions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-27T12:49:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006465","title":"Colorectal cancer genomics with primary and metastatic samples","description":"We performed whole genome sequencing of metastatic colorectal cancer from 16 patients. Normal adjacent tissue, primary tissue, and metastatic tissue were analyzed to uncover metastatic progression and difference between primary and distant metastatic lesions.","abstract":"We performed whole genome sequencing of metastatic colorectal cancer from 16 patients. Normal adjacent tissue, primary tissue, and metastatic tissue were analyzed to uncover metastatic progression and difference between primary and distant metastatic lesions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-27T12:49:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006466","title":"Multi-focal genomic dissection of synchronous primary and metastatic tissue from de novo metastatic prostate cancer","description":"De novo metastatic prostate cancer is highly aggressive, but the paucity of routinely-collected tissue in this setting has hindered genomic stratification and jeopardizes precision oncology efforts. Here, we leveraged a rare study of surgical intervention in 43 de novo metastatic prostate cancers to assess somatic genotype across 607 synchronous primary and metastatic tissue foci plus circulating tumor DNA. Intra-prostate heterogeneity was pervasive and impacted clinically-relevant genes, resulting in frequent discordance between select primary-restricted foci and synchronous metastases. Additional complexity was driven in several instances by polyclonal metastatic seeding from the reservoir of phylogenetically-related primary populations. When simulating standard clinical practice relying on a single tissue focus, genomic heterogeneity plus highly variable per-sample tumor fraction caused false genotyping of dominant disease. However, in silico modeling demonstrated that analysis of multiple biopsy cores can rescue misassigned somatic genotypes. Our results define the relationship between synchronous treatment-naive primary and metastatic lesions in de novo metastatic prostate cancer and provide a framework for implementing genomics-guided patient management.","abstract":"De novo metastatic prostate cancer is highly aggressive, but the paucity of routinely-collected tissue in this setting has hindered genomic stratification and jeopardizes precision oncology efforts. Here, we leveraged a rare study of surgical intervention in 43 de novo metastatic prostate cancers to assess somatic genotype across 607 synchronous primary and metastatic tissue foci plus circulating tumor DNA. Intra-prostate heterogeneity was pervasive and impacted clinically-relevant genes, resulting in frequent discordance between select primary-restricted foci and synchronous metastases. Additional complexity was driven in several instances by polyclonal metastatic seeding from the reservoir of phylogenetically-related primary populations. When simulating standard clinical practice relying on a single tissue focus, genomic heterogeneity plus highly variable per-sample tumor fraction caused false genotyping of dominant disease. However, in silico modeling demonstrated that analysis of multiple biopsy cores can rescue misassigned somatic genotypes. Our results define the relationship between synchronous treatment-naive primary and metastatic lesions in de novo metastatic prostate cancer and provide a framework for implementing genomics-guided patient management.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-27T22:11:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006467","title":"Sequence-based gene expression in uterine and ovarian carcinosarcomas","description":null,"abstract":"Gynecologic carcinosarcomas (CS), including more generally uterine (endometrial) and less frequently ovarian localization, are histologically defined as biphasic neoplasms composed of carcinomatous (C) epithelial and sarcomatous (S) malignant components. We report a comprehensive analysis of 20 patients of macro-dissected samples of C and S components through RNA sequencing.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006468","title":"OAC RNASeq","description":"Please see our related publication, 'Molecular profiling to predict immunochemotherapy outcomes in esophageal adenocarcinoma'","abstract":"Please see our related publication, 'Molecular profiling to predict immunochemotherapy outcomes in esophageal adenocarcinoma'","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-28T12:21:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006469","title":"OAC scRNASeq","description":"Please see our related publication, 'Molecular profiling to predict immunochemotherapy outcomes in esophageal adenocarcinoma'","abstract":"Please see our related publication, 'Molecular profiling to predict immunochemotherapy outcomes in esophageal adenocarcinoma'","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-28T12:21:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006470","title":"OAC WGS","description":"Please see our related publication, 'Molecular profiling to predict immunochemotherapy outcomes in esophageal adenocarcinoma'","abstract":"Please see our related publication, 'Molecular profiling to predict immunochemotherapy outcomes in esophageal adenocarcinoma'","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-28T12:21:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006471","title":"HCA_Immune_UAI_Paediatric_Spatial_Managed_Access","description":"Comparison of immune populations in adenoid tissue in patients with and without history of otitis media","abstract":"Comparison of immune populations in adenoid tissue in patients with and without history of otitis media","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-28T13:37:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006472","title":"Multiple Tissue Monitoring in Huntington disease - RNAseq fibroblasts","description":"We examined whether peripheral tissues can serve as a source of readily accessible biological signatures at the RNA and protein level in Huntington disease (HD) patients. Under the MTM-HD study we generated large, high-quality human datasets from skeletal muscle, skin and adipose tissue, as well as primary human fibroblast lines to probe molecular changes in human pre-manifest and early manifest HD patients. We document the involvement of inflammation, energy metabolism and extracellular vesicle homeostasis. This demonstrates the potential to identify biological signatures from peripheral tissues in HD suitable as biomarkers in clinical trials.","abstract":"We examined whether peripheral tissues can serve as a source of readily accessible biological signatures at the RNA and protein level in Huntington disease (HD) patients. Under the MTM-HD study we generated large, high-quality human datasets from skeletal muscle, skin and adipose tissue, as well as primary human fibroblast lines to probe molecular changes in human pre-manifest and early manifest HD patients. We document the involvement of inflammation, energy metabolism and extracellular vesicle homeostasis. This demonstrates the potential to identify biological signatures from peripheral tissues in HD suitable as biomarkers in clinical trials.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-29T10:17:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006473","title":"Multiple Tissue Monitoring in Huntington disease - RNAseq adipose tissue","description":"We examined whether peripheral tissues can serve as a source of readily accessible biological signatures at the RNA and protein level in Huntington disease (HD) patients. Under the MTM-HD study we generated large, high-quality human datasets from skeletal muscle, skin and adipose tissue, as well as primary human fibroblast lines to probe molecular changes in human pre-manifest and early manifest HD patients. We document the involvement of inflammation, energy metabolism and extracellular vesicle homeostasis. This demonstrates the potential to identify biological signatures from peripheral tissues in HD suitable as biomarkers in clinical trials.","abstract":"We examined whether peripheral tissues can serve as a source of readily accessible biological signatures at the RNA and protein level in Huntington disease (HD) patients. Under the MTM-HD study we generated large, high-quality human datasets from skeletal muscle, skin and adipose tissue, as well as primary human fibroblast lines to probe molecular changes in human pre-manifest and early manifest HD patients. We document the involvement of inflammation, energy metabolism and extracellular vesicle homeostasis. This demonstrates the potential to identify biological signatures from peripheral tissues in HD suitable as biomarkers in clinical trials.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-29T10:18:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006474","title":"Multiple Tissue Monitoring in Huntington disease - RNAseq skeletal muscle","description":"We examined whether peripheral tissues can serve as a source of readily accessible biological signatures at the RNA and protein level in Huntington disease (HD) patients. Under the MTM-HD study we generated large, high-quality human datasets from skeletal muscle, skin and adipose tissue, as well as primary human fibroblast lines to probe molecular changes in human pre-manifest and early manifest HD patients. We document the involvement of inflammation, energy metabolism and extracellular vesicle homeostasis. This demonstrates the potential to identify biological signatures from peripheral tissues in HD suitable as biomarkers in clinical trials.","abstract":"We examined whether peripheral tissues can serve as a source of readily accessible biological signatures at the RNA and protein level in Huntington disease (HD) patients. Under the MTM-HD study we generated large, high-quality human datasets from skeletal muscle, skin and adipose tissue, as well as primary human fibroblast lines to probe molecular changes in human pre-manifest and early manifest HD patients. We document the involvement of inflammation, energy metabolism and extracellular vesicle homeostasis. This demonstrates the potential to identify biological signatures from peripheral tissues in HD suitable as biomarkers in clinical trials.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-29T10:19:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006475","title":"HCA_Skin_Disease_HS_RNA_NCL","description":"HCA Deep dive of diseased human adult skin","abstract":"HCA Deep dive of diseased human adult skin - Hidradenitis Suppurativa","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006476","title":"Molecular_QTLs_of_Human_umbilical_vein_endothelial_cells__HUVECs__","description":"We aim to characterise the range of phenotypic variation in gene expression, epigenetic regulation and intermediate functional phenotypes and its underlying genetic determinants in primary Human umbilical vein endothelial cells (HUVECs) samples We will measure gene expression by RNA sequencing (RNA-seq), genome functionality by ATAC-sequencing (ATAC-seq, to determine which regions are in an open chromatin state) and by determining H3 lysine 27acetylation (H3K27ac), a marker of active transcriptional enhancers, localisation genome wide by chromatin immunoprecipitation coupled with sequencing (ChIP-seq).","abstract":"We aim to characterise the range of phenotypic variation in gene expression, epigenetic regulation and intermediate functional phenotypes and its underlying genetic determinants in primary Human umbilical vein endothelial cells (HUVECs) samples We will measure gene expression by RNA sequencing (RNA-seq), genome functionality by ATAC-sequencing (ATAC-seq, to determine which regions are in an open chromatin state) and by determining H3 lysine 27acetylation (H3K27ac), a marker of active transcriptional enhancers, localisation genome wide by chromatin immunoprecipitation coupled with sequencing (ChIP-seq).","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-29T12:52:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006477","title":"The HLA ligandome of oropharyngeal squamous cell carcinomas reveals shared tumor-exclusive peptides for semi-personalized vaccination","description":"Immunotherapeutic strategies provide promising tools for the development of novel treatment options for OPSCC patients. An accurate selection of suitable target antigens is essential for the development of novel antigen-specific immunotherapeutic approaches. The study is the first to apply immunopeptidomic strategies to OPSCC and reveals naturally HLA-presented, tumor-associated peptides. The MS-based approach provides direct evidence for HLA presentation of tumor-associated potential T cell targets. These findings may serve as a basis for the development of T-cell-based immunotherapies.","abstract":"Immunotherapeutic strategies provide promising tools for the development of novel treatment options for OPSCC patients. An accurate selection of suitable target antigens is essential for the development of novel antigen-specific immunotherapeutic approaches. The study is the first to apply immunopeptidomic strategies to OPSCC and reveals naturally HLA-presented, tumor-associated peptides. The MS-based approach provides direct evidence for HLA presentation of tumor-associated potential T cell targets. These findings may serve as a basis for the development of T-cell-based immunotherapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-29T16:32:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006478","title":"Tumor microenvironment study of ovarian granulosa cell tumors","description":"Adult-type granulosa cell tumors (aGCT) are rare ovarian sex cord tumors with few\n41 effective treatments for recurrent disease. \nThe objective of this study was to compare global gene expression profiles and characterize the tumor microenvironment (TME) of primary and recurrent aGCTs in order to identify correlates of disease recurrence. Total RNA sequencing was performed on 24 pathologically confirmed, cryopreserved aGCT samples, including 8 primary and 16 recurrent tumors. A total of 31 differentially expressed genes were identified between primary and recurrent aGCT. TME analysis demonstrated significantly higher fractions of neutrophils and macrophages in recurrent tumors in conjunction with significantly lower fractions of cancer-associated fibroblasts and endothelial cells.","abstract":"Adult-type granulosa cell tumors (aGCT) are rare ovarian sex cord tumors with few\n41 effective treatments for recurrent disease. \nThe objective of this study was to compare global gene expression profiles and characterize the tumor microenvironment (TME) of primary and recurrent aGCTs in order to identify correlates of disease recurrence. Total RNA sequencing was performed on 24 pathologically confirmed, cryopreserved aGCT samples, including 8 primary and 16 recurrent tumors. A total of 31 differentially expressed genes were identified between primary and recurrent aGCT. TME analysis demonstrated significantly higher fractions of neutrophils and macrophages in recurrent tumors in conjunction with significantly lower fractions of cancer-associated fibroblasts and endothelial cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-29T19:32:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006479","title":"Comprehensive de novo variant discovery with HiFi long-read sequencing","description":"We performed whole-genome sequencing of 8 trios with intellectual disability using Pacbio HiFi long-reads. We then called variants with PBSV and Deepvariant. We filtered for high-quality de novo variants and validated them.","abstract":"We performed whole-genome sequencing of 8 trios with intellectual disability using Pacbio HiFi long-reads. We then called variants with PBSV and Deepvariant. We filtered for high-quality de novo variants and validated them.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-07-30T14:00:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006480","title":"HCA_Skin_Disease_Atopic_dermatitis_Wellcome_DNA_Managed_Access","description":"Multiomics of skin and PBMC samples from eczema patients, pre and post dupilumab treatment","abstract":"Multiomics of skin and PBMC samples from eczema patients, pre and post dupilumab treatment","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006481","title":"HCA_Skin_Disease_Atopic_dermatitis_Wellcome_RNA_Managed_Access","description":"Multomics of skin and PBMC samples from eczema patients, pre and post dupilumab treatment","abstract":"Multiomics of skin and PBMC samples from eczema patients, pre and post dupilumab treatment","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006482","title":"HCA_Skin_Disease_Atopic_dermatitis_Wellcome_Spatial_Managed_Access","description":"Spatial transcriptomics of skin and PBMC samples from eczema patients, pre and post dupilumab treatment","abstract":"Multiomics of skin and PBMC samples from eczema patients, pre and post dupilumab treatment","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-02T11:18:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006483","title":"HCA_Oesophagus_Regeneration_CASM_RNA","description":"Transcriptomics study of regenerating oesophagus cells","abstract":"Characterising the genomic and phenotypic changes that define injury and repair in the context of early carcinogenesis in the human oesophagus (sponge cell sampling) using 10x single cell techniques.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006484","title":"Cambridge_CCLG_GERM_Cell_Tumour_Behjati_WellcomeCore_DNA_Manager_Access","description":"Nuclear single cell and Visium of RMS tumors.","abstract":"The aim of this study is to study the genomes of ultra rare childhood tumours","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006485","title":"scCRISPR-screen in human monocyte derived macrophages","description":"To determine whether the hits derived from a genome-wide murine BMDM screen regulated human macrophage phenotypes, we established a framework that coupled genetic perturbation with phenotypic analysis at single-cell resolution in primary human monocyte-derived macrophages (MDM scCRISPR-seq).","abstract":"To determine whether the hits derived from a genome-wide murine BMDM screen regulated human macrophage phenotypes, we established a framework that coupled genetic perturbation with phenotypic analysis at single-cell resolution in primary human monocyte-derived macrophages (MDM scCRISPR-seq).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006486","title":"Blina_Tumour_project","description":"The aim of this study is to reconstruct the embryology of childhood tumours.","abstract":"The aim of this study is to reconstruct the embryology of childhood tumours.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-03T10:00:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006487","title":"Characterization of Arabian Peninsula whole exomes","description":"We conducted whole exome sequencing (using the SureSelect Human All Exon V5 + UTRs target enrichment kit) of 90 individuals from AP (23 from Saudi Arabia, 24 from Yemen, 24 from Oman and 19 from UAE).","abstract":"We conducted whole exome sequencing (using the SureSelect Human All Exon V5 + UTRs target enrichment kit) of 90 individuals from AP (23 from Saudi Arabia, 24 from Yemen, 24 from Oman and 19 from UAE).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-04T15:34:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006488","title":"SPECIAL: Dissecting the melanoma ecosystem one cell at the time during immunotherapy","description":"The aim of this study was to identify potential biomarkers of response to immunotherapy (anti-PD1-based) as well as gain understanding of the biological mechanism of therapy resistance (either intrinsic or acquired) in melanoma patients.  Single cell RNA sequencing was performed from pre- and on-treatment (2-3 weeks after immunotherapy) metastatic biopsies from stage III and IV melanoma patients.","abstract":"The aim of this study was to identify potential biomarkers of response to immunotherapy (anti-PD1-based) as well as gain understanding of the biological mechanism of therapy resistance (either intrinsic or acquired) in melanoma patients.  Single cell RNA sequencing was performed from pre- and on-treatment (2-3 weeks after immunotherapy) metastatic biopsies from stage III and IV melanoma patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-05T11:02:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006489","title":"Colorectal cancer study","description":"Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and non-matrix proteins. Although most MMPs are secreted as inactive proenzymes and they are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway.  It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C&gt;T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11’s protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.","abstract":"Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and non-matrix proteins. Although most MMPs are secreted as inactive proenzymes and they are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway.  It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C&gt;T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11’s protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-05T16:34:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006490","title":"Somatic copy number alteration and fragmentation analysis in circulating tumor DNA for cancer screening and treatment monitoring in colorectal cancer patients","description":"Background: Analysis of circulating free DNA (cfDNA) is a promising tool for personalized management of colorectal cancer (CRC) patients. Untargeted cfDNA analysis using whole-genome sequencing (WGS) does not need a priori knowledge of the patient´s mutation profile. \n\nMethods: Here we established LIquid biopsy Fragmentation, Epigenetic signature and Copy Number Alteration analysis (LIFE-CNA) using WGS with ~6x coverage for detection of circulating tumor DNA (ctDNA) in CRC patients as a marker for CRC detection and monitoring. \n\nResults: We describe the analytical validity and a clinical proof-of-concept of LIFE-CNA using a total of 259 plasma samples collected from 50 patients with stage I-IV CRC and 61 healthy controls. To reliably distinguish CRC patients from healthy controls, we determined cutoffs for the detection of ctDNA based on global and regional cfDNA fragmentation patterns, transcriptionally active chromatin sites, and SCNAs. We further combined global and regional fragmentation pattern into a machine learning classifier to accurately predict ctDNA for cancer detection. By following individual patients throughout their course of disease, we show that LIFE-CNA enables the reliable prediction of response or resistance to treatment up to 3.5 months before commonly used CEA.\n\nConclusion: In summary, we developed and validated a sensitive and cost-effective method for untargeted ctDNA detection at diagnosis as well as for treatment monitoring of all CRC patients based on genetic as well as non-genetic tumor-specific cfDNA features. Thus, once sensitivity and specificity have been externally validated, LIFE-CNA has the potential to be implemented into clinical practice. To the best of our knowledge, this is the first study to consider multiple genetic and non-genetic cfDNA features in combination with ML classifiers and to evaluate their potential in both cancer detection and treatment monitoring.","abstract":"Background: Analysis of circulating free DNA (cfDNA) is a promising tool for personalized management of colorectal cancer (CRC) patients. Untargeted cfDNA analysis using whole-genome sequencing (WGS) does not need a priori knowledge of the patient´s mutation profile. \n\nMethods: Here we established LIquid biopsy Fragmentation, Epigenetic signature and Copy Number Alteration analysis (LIFE-CNA) using WGS with ~6x coverage for detection of circulating tumor DNA (ctDNA) in CRC patients as a marker for CRC detection and monitoring. \n\nResults: We describe the analytical validity and a clinical proof-of-concept of LIFE-CNA using a total of 259 plasma samples collected from 50 patients with stage I-IV CRC and 61 healthy controls. To reliably distinguish CRC patients from healthy controls, we determined cutoffs for the detection of ctDNA based on global and regional cfDNA fragmentation patterns, transcriptionally active chromatin sites, and SCNAs. We further combined global and regional fragmentation pattern into a machine learning classifier to accurately predict ctDNA for cancer detection. By following individual patients throughout their course of disease, we show that LIFE-CNA enables the reliable prediction of response or resistance to treatment up to 3.5 months before commonly used CEA.\n\nConclusion: In summary, we developed and validated a sensitive and cost-effective method for untargeted ctDNA detection at diagnosis as well as for treatment monitoring of all CRC patients based on genetic as well as non-genetic tumor-specific cfDNA features. Thus, once sensitivity and specificity have been externally validated, LIFE-CNA has the potential to be implemented into clinical practice. To the best of our knowledge, this is the first study to consider multiple genetic and non-genetic cfDNA features in combination with ML classifiers and to evaluate their potential in both cancer detection and treatment monitoring.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-05T17:47:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006491","title":"Control of Focal Adhesion Kinase Activation by RUNX1-regulated miRNAs in high-risk AML","description":"We recently described a 16-gene expression signature for improved risk stratification of acute myeloid leukemia (AML) patients called the AML Prognostic Score (APS). A subset of APS high-risk AML patients showed increased levels of focal adhesion kinase (FAK), encoded by the Protein Tyrosine Kinase 2 (PTK2) gene, which was correlated with RUNX1 mutations. RUNX1 mutant cells are more sensitive to PTK2 inhibitors. As we were not able to detect RUNX1 binding sites in the PTK2 promoter, we hypothesized that RUNX1 might regulate micro(mi)RNAs that repress PTK2, such that loss-of-function RUNX1 mutations would result in reduced miRNA expression and derepression of PTK2. Examination of paired RNA-seq and miRNA-seq data from 301 AML cases revealed two miRNAs that positively correlated with RUNX1 expression, contained RUNX1 binding sites in their promoters and were predicted to target PTK2. We show that the hsa-let7a-2-3p and hsa-miR-135a-5p promoters are regulated by RUNX1, and that PTK2 is a direct target of both miRNAs. Even in the absence of RUNX1 mutations, hsa-let7a-2-3p and hsa-miR-135a-5p regulate PTK2 expression, and reduced expression of these two miRNAs sensitizes AML cells to PTK2 inhibition. These data explain how RUNX1 regulates PTK2, and identify potential miRNA biomarkers for targeting AML with PTK2 inhibitors.","abstract":"We recently described a 16-gene expression signature for improved risk stratification of acute myeloid leukemia (AML) patients called the AML Prognostic Score (APS). A subset of APS high-risk AML patients showed increased levels of focal adhesion kinase (FAK), encoded by the Protein Tyrosine Kinase 2 (PTK2) gene, which was correlated with RUNX1 mutations. RUNX1 mutant cells are more sensitive to PTK2 inhibitors. As we were not able to detect RUNX1 binding sites in the PTK2 promoter, we hypothesized that RUNX1 might regulate micro(mi)RNAs that repress PTK2, such that loss-of-function RUNX1 mutations would result in reduced miRNA expression and derepression of PTK2. Examination of paired RNA-seq and miRNA-seq data from 301 AML cases revealed two miRNAs that positively correlated with RUNX1 expression, contained RUNX1 binding sites in their promoters and were predicted to target PTK2. We show that the hsa-let7a-2-3p and hsa-miR-135a-5p promoters are regulated by RUNX1, and that PTK2 is a direct target of both miRNAs. Even in the absence of RUNX1 mutations, hsa-let7a-2-3p and hsa-miR-135a-5p regulate PTK2 expression, and reduced expression of these two miRNAs sensitizes AML cells to PTK2 inhibition. These data explain how RUNX1 regulates PTK2, and identify potential miRNA biomarkers for targeting AML with PTK2 inhibitors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-06T02:58:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006492","title":"RNAseq analysis on metastatic Colorectal Cancer xenografts samples","description":null,"abstract":"Bank of metastatic colorectal cancer (mCRC) of Patient Derived Xenografts (PDXs)","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-08T10:45:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006493","title":"scBCR-seq of LUAD","description":null,"abstract":"The goal is to study the dynamics of B cell receptors and to learn how the B cell reptoire changed in early LUADs.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006494","title":"TRACERx NSCLC - Whole exome multiregion sequencing data","description":null,"abstract":"TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-09T13:14:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006495","title":"Upper cortical layer-driven network impairment in schizophrenia","description":"Schizophrenia is one of the most wide-spread and complex mental disorders. To characterize the impact of schizophrenia, we performed single nucleus RNA sequencing (snRNA-seq) of &gt;220,000 neurons from the dorsolateral prefrontal cortex of patients with schizophrenia and matched controls. Additionally, &gt;115,000 neurons were analyzed topographically by immunohistochemistry. Compositional analysis of snRNA-seq data revealed a reduction in abundance of GABAergic neurons\nand a concomitant increase in principal neurons, most pronounced for upper cortical layer subtypes, which was substantiated by histological analysis. Many neuronal subtypes showed extensive transcriptomic changes, the most dramatic - in upper layer GABAergic neurons, including downregulation in energy metabolism and upregulation in neurotransmission. Transcription factor network analysis demonstrated a developmental origin of transcriptomic changes. Finally, Visium\nspatial transcriptomics further corroborated upper layer neuron vulnerability in schizophrenia. Overall, our results point towards general network impairment within upper cortical layers as a core substrate associated with schizophrenia symptomatology. Study is available on bioRxiv (https://doi.org/10.1101/2020.11.17.386458) and in upcoming publication.","abstract":"Schizophrenia is one of the most wide-spread and complex mental disorders. To characterize the impact of schizophrenia, we performed single nucleus RNA sequencing (snRNA-seq) of &gt;220,000 neurons from the dorsolateral prefrontal cortex of patients with schizophrenia and matched controls. Additionally, &gt;115,000 neurons were analyzed topographically by immunohistochemistry. Compositional analysis of snRNA-seq data revealed a reduction in abundance of GABAergic neurons\nand a concomitant increase in principal neurons, most pronounced for upper cortical layer subtypes, which was substantiated by histological analysis. Many neuronal subtypes showed extensive transcriptomic changes, the most dramatic - in upper layer GABAergic neurons, including downregulation in energy metabolism and upregulation in neurotransmission. Transcription factor network analysis demonstrated a developmental origin of transcriptomic changes. Finally, Visium\nspatial transcriptomics further corroborated upper layer neuron vulnerability in schizophrenia. Overall, our results point towards general network impairment within upper cortical layers as a core substrate associated with schizophrenia symptomatology. Study is available on bioRxiv (https://doi.org/10.1101/2020.11.17.386458) and in upcoming publication.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-09T15:33:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006496","title":"scRNA-Seq of Breast cancer CAF-S4/CAP cells","description":"Single-cell RNA-Seq data of CAF-S4 / CAP cells isolated from a total of 3 primary BC (surgical residues prior any treatment)","abstract":"Single-cell RNA-Seq data of CAF-S4 / CAP cells isolated from a total of 3 primary BC (surgical residues prior any treatment)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006497","title":"Bulk RNA-seq of stromal cells from multiple cancer types","description":"We sorted CD45-CD44+CD90+ stromal cells from multiple tumor types and performed bulk RNA-seq. The data allows to infer CAF programs active across indications.","abstract":"We sorted CD45-CD44+CD90+ stromal cells from multiple tumor types and performed bulk RNA-seq. The data allows to infer CAF programs active across indications.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-10T17:22:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006498","title":"Finding structural variation from the human skin fibroblast at the single-cell level","description":"Somatic structural variants (SVs) are widespread in cancer, but their impact on disease evolution is understudied due to a lack of methods to directly characterize their molecular consequences. We present a computational method, scNOVA, that integrates haplotype-resolved SV discovery with nucleosome occupancy analysis using Strand-seq, to functionally characterize SVs in single cells.","abstract":"Somatic structural variants (SVs) are widespread in cancer, but their impact on disease evolution is understudied due to a lack of methods to directly characterize their molecular consequences. We present a computational method, scNOVA, that integrates haplotype-resolved SV discovery with nucleosome occupancy analysis using Strand-seq, to functionally characterize SVs in single cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-10T19:00:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006499","title":"The Extracellular RNA Quality Control (exRNAQC) study (phase 2)","description":null,"abstract":"The use of blood-based extracellular RNA (exRNA) as clinical biomarker requires the implementation of a validated procedure for sample collection, processing and profiling. So far, no study has systematically addressed the pre-analytical variables affecting transcriptome analysis of exRNAs. In the first phase of the exRNAQC study, we evaluated 10 blood collection tubes, 3 time points between blood draw and downstream processing, and 8 RNA purification methods using the supplier-specified minimum and maximum biofluid input volumes. The impact of these pre-analytics is assessed by deep transcriptome profiling of both small and messenger RNA from healthy donors' plasma or serum. In this second phase, we assessed interactions between blood collection tubes, time points and purification methods.\n\nMore project info on bioRxiv (manuscript title: Performance of RNA purification kits and blood collection tubes in the Extracellular RNA Quality Control (exRNAQC) study) and https://oncornalab.ugent.be/project/exrnaqc/","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-11T11:13:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006500","title":"DERMATLAS__Syringocystadenoma_papilliferum_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are syringocystadenoma papilliferum (SCAP).","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are syringocystadenoma papilliferum (SCAP).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006501","title":"Long-term temporal stability of peripheral blood DNA methylation alterations in patients with inflammatory bowel disease.","description":"Introduction\nThere is great current interest in the potential application of DNA methylation alterations in peripheral blood as biomarkers of susceptibility, progression, and treatment response in inflammatory bowel disease (IBD). To date, the intra-individual stability of peripheral blood leukocyte (PBL) methylation in IBD patients, a key consideration in biomarker development, has not been characterised. Here, we studied the long-term stability of all probes located on the Illumina HumanMethylation EPIC BeadChip array.   \n\nMethods\nWe followed a cohort of 46 adult IBD patients (36 Crohn’s disease (CD), 10 ulcerative colitis (UC), median age 44 (IQR: 27-56), 50% female) that received standard care without any intervention at the Amsterdam UMC. Paired PBL samples were collected at two time points with a median 7 (range: 2-9) years in between. Differential methylation and intra-class correlation (ICC) analyses were used to identify time-associated differences and temporally stable CpGs, respectively. \n\nResults \nAround 60% of all CpG loci on the EPIC array presented poor (ICC &lt;0.50); 119,388 (≈14%) and 41,274 (≈5%) showed good (ICC ≥0.75) or excellent (ICC ≥0.90) intra-individual stability. Functional over-representation analyses of the stable methylated CpGs implicated genes involved in cell-cell signaling, adhesion and neurogenesis. Focusing on previously identified consistently differentially methylated positions indicated that 22 CD-, 11 UC-, and 24 IBD-associated loci demonstrated good stability (ICC ≥0.75) over time, where we observed a marked stability of CpG loci associated to the HLA genes.  \n\nConclusion\nOur data provide insight into the long-term stability of the PBL DNA methylome within an IBD context, facilitating the selection of biologically relevant and robust IBD-associated epigenetic biomarkers with increased potential for independent validation.","abstract":"Introduction\nThere is great current interest in the potential application of DNA methylation alterations in peripheral blood as biomarkers of susceptibility, progression, and treatment response in inflammatory bowel disease (IBD). To date, the intra-individual stability of peripheral blood leukocyte (PBL) methylation in IBD patients, a key consideration in biomarker development, has not been characterised. Here, we studied the long-term stability of all probes located on the Illumina HumanMethylation EPIC BeadChip array.   \n\nMethods\nWe followed a cohort of 46 adult IBD patients (36 Crohn’s disease (CD), 10 ulcerative colitis (UC), median age 44 (IQR: 27-56), 50% female) that received standard care without any intervention at the Amsterdam UMC. Paired PBL samples were collected at two time points with a median 7 (range: 2-9) years in between. Differential methylation and intra-class correlation (ICC) analyses were used to identify time-associated differences and temporally stable CpGs, respectively. \n\nResults \nAround 60% of all CpG loci on the EPIC array presented poor (ICC &lt;0.50); 119,388 (≈14%) and 41,274 (≈5%) showed good (ICC ≥0.75) or excellent (ICC ≥0.90) intra-individual stability. Functional over-representation analyses of the stable methylated CpGs implicated genes involved in cell-cell signaling, adhesion and neurogenesis. Focusing on previously identified consistently differentially methylated positions indicated that 22 CD-, 11 UC-, and 24 IBD-associated loci demonstrated good stability (ICC ≥0.75) over time, where we observed a marked stability of CpG loci associated to the HLA genes.  \n\nConclusion\nOur data provide insight into the long-term stability of the PBL DNA methylome within an IBD context, facilitating the selection of biologically relevant and robust IBD-associated epigenetic biomarkers with increased potential for independent validation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-12T09:52:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006502","title":"Immune microenvironment and lineage tracing help deciphering Rosette-forming GlioNeuronal Tumors: a multi-omic analysis of 9 cases","description":"Rosette-forming GlioNeuronal Tumor (RGNT) is a rare central nervous system neoplasm containing two components, glial and neuronal. The delineation of histological diagnosis of RGNT from similar low-grade tumors such as pilocytic astrocytoma (PA) and ganglioglioma (GG) may be challenging. We performed here a comprehensive molecular analysis of a cohort of tumors with same histology features to identify molecular characteristics of RGNT. \nA cohort of 9 rosette-forming tumors histologically-diagnosed were analyzed at molecular level using multimodal approaches as Whole Exome Sequencing (WES), RNAseq and methylome. In our cohort, 3 tumors were plotted within the Methylation Class-RGNT (MC-RGNT) characterized by FGFR1 mutation associated with PIK3CA or NF1 mutations. Transcriptome analysis was performed in 7 cases. RNAseq identified a “Hot” and a “Cold” transcriptomic group; the latter includes the 3 MC-RGNT and 1 MC-Pilocytic Astrocytoma and exhibited a “Cold” immune tumor microenvironment in comparison with the “Hot” group. The distinct immune cell content of both groups was confirmed by quantitative immunostainings. Get Set Enrichment Analysis showed that the “Cold” group had upregulated NOTCH pathway and mainly oligodendrocyte precursor cell and neuronal phenotypes while the “Hot” group exhibited predominantly astrocytic and neural stem cell phenotypes. In silico deconvolution identified the cerebellar granule cell lineage as a putative origin and as the cell context to understand the effects of genetic alterations and NOTCH signaling. \nHistological diagnosis of rosette-forming tumors encompasses heterogeneous tumor entities. Our study identified distinct tumor cell contexts and microenvironments as key features to better understand and manage these neoplasms.","abstract":"Rosette-forming GlioNeuronal Tumor (RGNT) is a rare central nervous system neoplasm containing two components, glial and neuronal. The delineation of histological diagnosis of RGNT from similar low-grade tumors such as pilocytic astrocytoma (PA) and ganglioglioma (GG) may be challenging. We performed here a comprehensive molecular analysis of a cohort of tumors with same histology features to identify molecular characteristics of RGNT. \nA cohort of 9 rosette-forming tumors histologically-diagnosed were analyzed at molecular level using multimodal approaches as Whole Exome Sequencing (WES), RNAseq and methylome. In our cohort, 3 tumors were plotted within the Methylation Class-RGNT (MC-RGNT) characterized by FGFR1 mutation associated with PIK3CA or NF1 mutations. Transcriptome analysis was performed in 7 cases. RNAseq identified a “Hot” and a “Cold” transcriptomic group; the latter includes the 3 MC-RGNT and 1 MC-Pilocytic Astrocytoma and exhibited a “Cold” immune tumor microenvironment in comparison with the “Hot” group. The distinct immune cell content of both groups was confirmed by quantitative immunostainings. Get Set Enrichment Analysis showed that the “Cold” group had upregulated NOTCH pathway and mainly oligodendrocyte precursor cell and neuronal phenotypes while the “Hot” group exhibited predominantly astrocytic and neural stem cell phenotypes. In silico deconvolution identified the cerebellar granule cell lineage as a putative origin and as the cell context to understand the effects of genetic alterations and NOTCH signaling. \nHistological diagnosis of rosette-forming tumors encompasses heterogeneous tumor entities. Our study identified distinct tumor cell contexts and microenvironments as key features to better understand and manage these neoplasms.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-12T16:35:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006503","title":"Histone modifications of cfDNA","description":null,"abstract":"Histone modifications of cfDNA","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-15T02:41:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006504","title":"Whole exome sequencing data of patients with resectable esophageal adenocarcinoma treated with neoadjuvant atezolizumab and chemoradiation (PERFECT)","description":"Whole exome sequencing was performed on matched tumor and normal DNA of patients with resectable esophageal adenocarcinoma that particpated in the PERFECT trial. The PERFECT trial is an open-label, single-arm, multicenter, phase II feasibility study (NCT03087864) investigating the safety and efficacy of atezolizumab, combined with neoadjuvant chemoradiotherapy and subsequent esophagectomy.","abstract":"Whole exome sequencing was performed on matched tumor and normal DNA of patients with resectable esophageal adenocarcinoma that particpated in the PERFECT trial. The PERFECT trial is an open-label, single-arm, multicenter, phase II feasibility study (NCT03087864) investigating the safety and efficacy of atezolizumab, combined with neoadjuvant chemoradiotherapy and subsequent esophagectomy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-03-12T15:08:08.253651+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006505","title":"NB evolution","description":null,"abstract":"Here, we quantify the somatic evolution of neuroblastomas\nby whole-genome sequencing, molecular clock analysis and population-genetic\nmodeling","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006506","title":"Solve-RD Cohort 1 ITHACA DF1+2 v1","description":null,"abstract":"Solve-RD data submitted to the ERN-ITHACA cohort for re-analysis (Data freeze 1+2) v1","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006507","title":"Solve-RD Cohort 1 GENTURIS DF1+2 v1","description":null,"abstract":"Solve-RD data submitted to the ERN-GENTURIS cohort for re-analysis (Data freeze 1+2) v1","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006508","title":"Solve-RD Cohort 1 EuroNMD DF1+2 v1","description":null,"abstract":"Solve-RD data submitted to the ERN-EuroNMD cohort for re-analysis (Data freeze 1+2) v1","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006509","title":"Solve-RD Cohort 1 RND DF1+2 v1","description":null,"abstract":"Solve-RD data submitted to the ERN-RND cohort for re-analysis (Data freeze 1+2) v1","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006510","title":"Reliable assessment of telomere maintenance mechanisms in neuroblastoma","description":"Telomere maintenance mechanisms (TMM) are a hallmark of high-risk neuroblastoma, and are conferred by activation of telomerase or alternative lengthening of telomeres (ALT). However, detection of TMM is not yet part of the clinical routine, and consensus on TMM detection, especially on ALT assessment, remains to be achieved.\nWe here propose a workflow to reliably detect TMM in neuroblastoma. We show that unambiguous classification is feasible following a stepwise approach that determines both, activation of telomerase and ALT. The workflow proposed in this study can be used in clinical routine and provides a framework to systematically and reliably determine telomere maintenance mechanisms for risk stratification and treatment allocation of neuroblastoma patients.","abstract":"Telomere maintenance mechanisms (TMM) are a hallmark of high-risk neuroblastoma, and are conferred by activation of telomerase or alternative lengthening of telomeres (ALT). However, detection of TMM is not yet part of the clinical routine, and consensus on TMM detection, especially on ALT assessment, remains to be achieved.\nWe here propose a workflow to reliably detect TMM in neuroblastoma. We show that unambiguous classification is feasible following a stepwise approach that determines both, activation of telomerase and ALT. The workflow proposed in this study can be used in clinical routine and provides a framework to systematically and reliably determine telomere maintenance mechanisms for risk stratification and treatment allocation of neuroblastoma patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-17T15:43:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006511","title":"ATAC-Seq on OCIAML-22 Fractions","description":"The donor AML patient (unsorted) that was used to generate OCI-AML22 was expanded for 3-4 months, then sorted for the indicated fraction (CD34p: CD34+; CD34m: CD34-)","abstract":"The donor AML patient (unsorted) that was used to generate OCI-AML22 was expanded for 3-4 months, then sorted for the indicated fraction (CD34p: CD34+; CD34m: CD34-)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-17T16:06:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006512","title":"RNA-Seq on OCIAML-22 Fractions","description":"The donor AML patient (unsorted) that was used to generate OCI-AML22 was expanded for the indicated number of days (Donor: 0 day, 12d: 12 days, 2m: 2 months, 3m: 3 months), then sorted for the indicated fraction (CD34p: CD34+; CD34m: CD34-, CD38m: CD38-, CD38m: CD38-).","abstract":"The donor AML patient (unsorted) that was used to generate OCI-AML22 was expanded for the indicated number of days (Donor: 0 day, 12d: 12 days, 2m: 2 months, 3m: 3 months), then sorted for the indicated fraction (CD34p: CD34+; CD34m: CD34-, CD38m: CD38-, CD38m: CD38-).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-17T16:06:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006513","title":"Whole Genome Sequencing on OCIAML-22","description":"Donor_OCIAML22_bulk: The donor (unsorted) that was used to generate OCI-AML22.\n\nOCI-AML22_bulk_1month_inVitro: The donor (unsorted) that was used to generate OCI-AML22 was expanded for 1 month in vitro, then sequenced.\n\nOCI-AML22_graft_CD34minus_WGS: The donor (unsorted) that was used to generate OCI-AML22 was expanded for 1 month in vitro, then injected in NSG-SGM3 mice. 21 weeks after injection, cells from 5 mice injected with 5 mice injected with 1475 cells per mice and 4 mice injected with 469 cells per mice were sorted. The human CD34- fraction was sequenced (CD45h+CD45m-7aad-annexinV-CD34-)\n\nOCI-AML22_graft_CD34positive_WGS: The donor (unsorted) that was used to generate OCI-AML22 was expanded for 1 month in vitro, then injected in NSG-SGM3 mice. 21 weeks after injection, cells from 5 mice injected with 5 mice injected with 1475 cells per mice and 4 mice injected with 469 cells per mice were sorted. The human CD34+ fraction was sequenced (CD45h+CD45m-7aad-annexinV-CD34+)","abstract":"Donor_OCIAML22_bulk: The donor (unsorted) that was used to generate OCI-AML22.\n\nOCI-AML22_bulk_1month_inVitro: The donor (unsorted) that was used to generate OCI-AML22 was expanded for 1 month in vitro, then sequenced.\n\nOCI-AML22_graft_CD34minus_WGS: The donor (unsorted) that was used to generate OCI-AML22 was expanded for 1 month in vitro, then injected in NSG-SGM3 mice. 21 weeks after injection, cells from 5 mice injected with 5 mice injected with 1475 cells per mice and 4 mice injected with 469 cells per mice were sorted. The human CD34- fraction was sequenced (CD45h+CD45m-7aad-annexinV-CD34-)\n\nOCI-AML22_graft_CD34positive_WGS: The donor (unsorted) that was used to generate OCI-AML22 was expanded for 1 month in vitro, then injected in NSG-SGM3 mice. 21 weeks after injection, cells from 5 mice injected with 5 mice injected with 1475 cells per mice and 4 mice injected with 469 cells per mice were sorted. The human CD34+ fraction was sequenced (CD45h+CD45m-7aad-annexinV-CD34+)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-17T16:06:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006514","title":"Molecular heterogeneity and commonalities in pancreatic cancer precursors with gastric and intestinal phenotype","description":null,"abstract":"Due to the limited number of modifiable risk factors, secondary prevention strategies based on early diagnosis represent the preferred route to improve the prognosis of pancreatic ductal adenocarcinoma (PDAC). Here, we provide a comparative morphogenetic analysis of PDAC precursors aiming at dissecting the process of carcinogenesis and tackling the heterogeneity of preinvasive lesions.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006515","title":"Teratoma_LCM_RNA","description":"RNA sequencing across a number of different germ cell tumours, included mixed components within the same tumour.","abstract":"This study aims to characterise the transcriptomic profile of germ cell tumours, in particular to develop a phylogenetic tree within mixed germ cell tumours to provide insight into their development and cell of origin, both of which are currently poorly understood","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006516","title":"LFS_tumour_LCM_RNA","description":"CM RNA-seq from human tumour samples aimed at characterising the expression landscape within tumours in patients with inherited cancer predisposition.","abstract":"Li-Fraumeni Syndrome (LFS) is caused by germline variants in tp53 leading to susceptibility to a multitude of cancer types including sarcoma, breast cancer, brain tumours, and adrenocortical carcinomas. Lifetime risk of cancer development in LFS is ~80% for men and ~100% for women. The aim of this study is to understand the timings of key driver events and transcriptional profiles in germline tp53 tumourigenesis and to identify novel opportunities for screening and treatment.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006517","title":"Multi-region RNA sequencing of tumour regions and tumour-adjacent normal lung tissue","description":"TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC).","abstract":"TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-19T12:10:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006518","title":"Gene signature for predicting homologous recombination deficiency in triple-negative breast cancer","description":"We developed a gene expression-based classifier for homologous recombination deficiency (HRD) in breast cancer patients using WES and RNA-seq data obtained from 94 TNBC samples from a Malaysian hospital-based cohort (MyBrCa). This classifier was able to predict for high levels of a mutational signature associated with HRD in an additional MyBrCa TNBC validation cohort (this EGA study) as well as in TNBCs from TCGA. We also validated the classifier on a NanoString platform with both fresh frozen and FFPE tissue.","abstract":"We developed a gene expression-based classifier for homologous recombination deficiency (HRD) in breast cancer patients using WES and RNA-seq data obtained from 94 TNBC samples from a Malaysian hospital-based cohort (MyBrCa). This classifier was able to predict for high levels of a mutational signature associated with HRD in an additional MyBrCa TNBC validation cohort (this EGA study) as well as in TNBCs from TCGA. We also validated the classifier on a NanoString platform with both fresh frozen and FFPE tissue.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-19T13:28:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006519","title":"Genetic variants of the COL4A3, COL4A4, and COL4A5 genes contribute to thinned glomerular basement membrane lesions in sporadic IgA nephropathy patients","description":"Contribution of pathogenic COL4A3/COL4A4/COL4A5 variants to sporadic IgAN is still unclear. Whole exome sequencing was performed in sporadic IgAN patients with thinned glomerular basement membrane lesions and variations in COL4A3/COL4A4/COL4A5 genes were screened and evaluated. 37 different diagnostic variants in COL4A3/COL4A4/COL4A5 gene in 38 patients (31.1%) were identified.","abstract":"Contribution of pathogenic COL4A3/COL4A4/COL4A5 variants to sporadic IgAN is still unclear. Whole exome sequencing was performed in sporadic IgAN patients with thinned glomerular basement membrane lesions and variations in COL4A3/COL4A4/COL4A5 genes were screened and evaluated. 37 different diagnostic variants in COL4A3/COL4A4/COL4A5 gene in 38 patients (31.1%) were identified.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-22T03:23:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006520","title":"ATAC-seq/ChIP part","description":"Epigenetics: ATAC-seq and ChIP-seq data","abstract":"Epigenetics: ATAC-seq and ChIP-seq data","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-22T09:49:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006521","title":"RNA-seq SE","description":"Transcriptomics of single-end RNA-seq data","abstract":"Transcriptomics of single-end RNA-seq data","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-22T09:49:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006522","title":"RNA-seq PE","description":"Transcriptomics of paired-end RNA-seq data","abstract":"Transcriptomics of paired-end RNA-seq data","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-22T09:49:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006523","title":"RRBS data from TRACERx non-small cell lung cancer (NSCLC) tumours and matched normal adjacent tissue.","description":"TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC). \n\nThis study looks at multi-region RRBS data from the TRACERx cohort selected for quantity of material available and high tumour purity","abstract":"TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC). \n\nThis study looks at multi-region RRBS data from the TRACERx cohort selected for quantity of material available and high tumour purity","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-22T21:33:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006524","title":"Identification of an age-related Parkinson’s disease risk factor that regulates sulfur metabolism","description":null,"abstract":"To better understand age-related PD pathogenesis, we modeled PD with directly reprogrammed dopaminergic neurons (iDA) which preserve donor aging signatures. By transcriptome analysis and immunohistochemistry on postmortem tissues, we identified a sulfurtransferase, TSTD1, to be upregulated in aged and diseased individuals. TSTD1 catalyzes sulfur transfer from thiosulfate to glutathione (GSH). GSH and cysteine were significantly decreased in dopaminergic (DA) neurons with TSTD1 overexpression. We hypothesize that TSTD1 upregulation in aged and PD individuals could disrupt sulfur metabolism which compromises anti-oxidant capacity and energy production in neurons; both of these mechanisms have been implicated as triggers for DA neuronal degeneration in PD.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006525","title":"test","description":null,"abstract":"dsad","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006526","title":"Paired WGS data from Wilms Tumors","description":"Paired whole genome sequencing tumor normal samples of pediatric Wilms tumors","abstract":"Paired whole genome sequencing tumor normal samples of pediatric Wilms tumors","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-23T15:49:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006527","title":"Characterization of Leukemic Stem Cells in DNMT3Amut and NPM1mut AMLs","description":"Trascriptomic profile of FACS-sorted LSCs from diagnostic DNMT3Amut and NPM1mut AML patients using a novel sorting strategy. Briefly, positive selection for GPR56 and a negative selection for NKG2DLigands were used to enrich for LSCs in both CD34+ and CD34- subpopulations. Primary samples were retrospectively collected based on their mutational profile.","abstract":"Trascriptomic profile of FACS-sorted LSCs from diagnostic DNMT3Amut and NPM1mut AML patients using a novel sorting strategy. Briefly, positive selection for GPR56 and a negative selection for NKG2DLigands were used to enrich for LSCs in both CD34+ and CD34- subpopulations. Primary samples were retrospectively collected based on their mutational profile.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-23T16:12:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006528","title":"Renal Cell Carcinoma Tumors From S-TRAC trial (NCT00375674) Whole Transcriptome Sequencing","description":"We report a comprehensive genomic and transcriptomic analysis of tumor samples from 171 patients at high risk for recurrent renal cell carcinoma post nephrectomy from the S-TRAC trial (NCT00375674). We identify gene expression signatures, including STRAC11 (derived from the sunitinib-treated population). The overlap in key elements captured in these gene expression signatures, which include genes representative of the tumor stroma microenvironment, regulatory T cell, and myeloid cells, suggests they are likely to be both prognostic and predictive of the anti-angiogenic effect in the adjuvant setting. These signatures also point to the identification of potential therapeutic targets for development in adjuvant renal cell carcinoma, such as MERTK and TDO2. Finally, our findings suggest that while anti-angiogenic adjuvant therapy might be important, it may not be sufficient to prevent recurrence and other factors such as immune response and that tumor environment may be of greater importance.","abstract":"We report a comprehensive genomic and transcriptomic analysis of tumor samples from 171 patients at high risk for recurrent renal cell carcinoma post nephrectomy from the S-TRAC trial (NCT00375674). We identify gene expression signatures, including STRAC11 (derived from the sunitinib-treated population). The overlap in key elements captured in these gene expression signatures, which include genes representative of the tumor stroma microenvironment, regulatory T cell, and myeloid cells, suggests they are likely to be both prognostic and predictive of the anti-angiogenic effect in the adjuvant setting. These signatures also point to the identification of potential therapeutic targets for development in adjuvant renal cell carcinoma, such as MERTK and TDO2. Finally, our findings suggest that while anti-angiogenic adjuvant therapy might be important, it may not be sufficient to prevent recurrence and other factors such as immune response and that tumor environment may be of greater importance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-23T18:52:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006529","title":"Renal Cell Carcinoma Tumors From S-TRAC trial (NCT00375674) Exome Sequencing","description":"We report a comprehensive genomic and transcriptomic analysis of tumor samples from 171 patients at high risk for recurrent renal cell carcinoma post nephrectomy from the S-TRAC trial (NCT00375674). We identify gene expression signatures, including STRAC11 (derived from the sunitinib-treated population). The overlap in key elements captured in these gene expression signatures, which include genes representative of the tumor stroma microenvironment, regulatory T cell, and myeloid cells, suggests they are likely to be both prognostic and predictive of the anti-angiogenic effect in the adjuvant setting. These signatures also point to the identification of potential therapeutic targets for development in adjuvant renal cell carcinoma, such as MERTK and TDO2. Finally, our findings suggest that while anti-angiogenic adjuvant therapy might be important, it may not be sufficient to prevent recurrence and other factors such as immune response and that tumor environment may be of greater importance.","abstract":"We report a comprehensive genomic and transcriptomic analysis of tumor samples from 171 patients at high risk for recurrent renal cell carcinoma post nephrectomy from the S-TRAC trial (NCT00375674). We identify gene expression signatures, including STRAC11 (derived from the sunitinib-treated population). The overlap in key elements captured in these gene expression signatures, which include genes representative of the tumor stroma microenvironment, regulatory T cell, and myeloid cells, suggests they are likely to be both prognostic and predictive of the anti-angiogenic effect in the adjuvant setting. These signatures also point to the identification of potential therapeutic targets for development in adjuvant renal cell carcinoma, such as MERTK and TDO2. Finally, our findings suggest that while anti-angiogenic adjuvant therapy might be important, it may not be sufficient to prevent recurrence and other factors such as immune response and that tumor environment may be of greater importance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-23T18:52:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006530","title":"Complex patterns of genomic heterogeneity identified in 42 tumor samples and ctDNA of a pulmonary atypical carcinoid patient","description":null,"abstract":"This study describes genomic tumor evolution and dissemination of a pulmonary carcinoid donated by a single generous patient. It highlights the critical role of chromosomal alterations in tumor initiation and the potential of ctDNA analysis to represent genomically heterogeneous disease.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-23T23:32:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006531","title":"Bulk RNA data from Wilms Tumors","description":"Bulk RNA-seq data of pediatric Wilms tumors","abstract":"Bulk RNA-seq data of pediatric Wilms tumors","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-24T10:57:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006532","title":"Somatic Inactivation of Breast Cancer Predisposition Genes in Tumours Associated with Pathogenic Germline Variants","description":"Breast cancers (BC) from susceptibility gene carriers, including BRCA1/2, PALB2 and RAD51C, have been shown to have bi-allelic loss in the respective genes and be associated with triple-negative (TN) BC and distinctive somatic mutational signatures. Tumour sequencing thus presents an orthogonal approach to assess the role of candidate genes in BC development.","abstract":"Breast cancers (BC) from susceptibility gene carriers, including BRCA1/2, PALB2 and RAD51C, have been shown to have bi-allelic loss in the respective genes and be associated with triple-negative (TN) BC and distinctive somatic mutational signatures. Tumour sequencing thus presents an orthogonal approach to assess the role of candidate genes in BC development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-24T12:50:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006533","title":"Neuroblastoma Evolution","description":"Here, we quantify the somatic evolution of neuroblastomas by deep (80x) whole-genome sequencing, molecular clock analysis and population-genetic modeling in a comprehensive cohort (Hipo_K09R) covering all subtypes.","abstract":"Here, we quantify the somatic evolution of neuroblastomas by deep (80x) whole-genome sequencing, molecular clock analysis and population-genetic modeling in a comprehensive cohort (Hipo_K09R) covering all subtypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-24T15:25:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006534","title":"Single-cell RNA-seq of human kidney tumors","description":"The aim of this study is to analyze the transcriptomic information of fresh single cells originating from human clear cell renal cell carcinomas (ccRCC). Samples have been experimentally enriched in malignant cells in order to address specific questions regarding heterogeneity and clonality in ccRCC. Samples include one set of long-term frozen and thawed single cells in order to explore the impact of liquid nitrogen freezing on ccRCC single cells.","abstract":"The aim of this study is to analyze the transcriptomic information of fresh single cells originating from human clear cell renal cell carcinomas (ccRCC). Samples have been experimentally enriched in malignant cells in order to address specific questions regarding heterogeneity and clonality in ccRCC. Samples include one set of long-term frozen and thawed single cells in order to explore the impact of liquid nitrogen freezing on ccRCC single cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-25T09:59:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006535","title":"Characterizing the tumor immune microenvironment of ependymomas using targeted gene expression profiles and RNA-sequencing the pros and cons","description":"RNA sequencing data of a collection of 6 pediatric ependymoma cases","abstract":"RNA sequencing data of a collection of 6 pediatric ependymoma cases","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-25T12:57:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006536","title":"Breast_quadrants_WGS","description":"This study aims to define the molecular features of normal breast tissues in individuals with evidence of BRCA1 promoter methylation.","abstract":"Recent research has identified BRCA1 promoter methylation in cord blood at levels consistent with mosaicism. BRCA1 methylation in blood  is also associated with an elevated risk of high grade serous ovarian cancer and triple negative breast cancer. However, how BRCA1 methylation spatially manifests in breast tissue is unclear. In this study we aim to establish whether this marker is detectable in normal and cancerous breast tissues and if it is, what spatial patterns it might takes. This will be achieved using a cohort of breast tissue samples from individuals with breast cancer. Samples of normal tissue were obtained from all four quadrants of the breast. We will ascertain the genomic and epigenetic features of both tumours and microscopic anatomical regions of the normal breast. We will identify mutational signatures that indicate the functional loss of BRCA1 and construct spatial maps of epigenetic and genetic features.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006537","title":"single nuclei RNASeq of 5 regions of the human prenatal brain","description":"Data generated through single nuclei RNA sequencing on 5 regions of the brain (frontal cortex, ganglionic eminence, hippocampus, thalamus and cerebellum) from 3 fetuses (two of 14 and one of 15 post-conception weeks, all female). Tissue was acquired from the MRC-Wellcome Trust Human Developmental Biology Resource (HDBR) with ethical approval.  \n\nsnRNA-seq libraries were prepared from ∼10,000 nuclei from each sample using Chromium Single Cell 3ʹ (v3) reagents (10X Genomics). Quality control of libraries was performed using the Agilent 5200 Fragment Analyzer before sequencing on an Illumina NovaSeq 6000 to a depth of at least 865 million (median = 1.01 billion) read pairs per library. Raw sequencing data were converted into FASTQ files.\n\nFor a full description of data generation, please see Cameron et al, Biological Psychiatry 2022, https://doi.org/10.1016/j.biopsych.2022.06.033.","abstract":"Data generated through single nuclei RNA sequencing on 5 regions of the brain (frontal cortex, ganglionic eminence, hippocampus, thalamus and cerebellum) from 3 fetuses (two of 14 and one of 15 post-conception weeks, all female). Tissue was acquired from the MRC-Wellcome Trust Human Developmental Biology Resource (HDBR) with ethical approval.  \n\nsnRNA-seq libraries were prepared from ∼10,000 nuclei from each sample using Chromium Single Cell 3ʹ (v3) reagents (10X Genomics). Quality control of libraries was performed using the Agilent 5200 Fragment Analyzer before sequencing on an Illumina NovaSeq 6000 to a depth of at least 865 million (median = 1.01 billion) read pairs per library. Raw sequencing data were converted into FASTQ files.\n\nFor a full description of data generation, please see Cameron et al, Biological Psychiatry 2022, https://doi.org/10.1016/j.biopsych.2022.06.033.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-25T21:28:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006538","title":"Single-cell multi-omics of relapse/refractory multiple myeloma patients (Hipo K08K/H067/K43R)","description":"Therapy resistance in cancers is ingrained in complex clonal dynamics. While the major clonal population in a tumour might respond well to the employed intervention, minor clones will eventually mutate, consequently acquiring a selective advantage and drug resistance. Hence, to improve cancer therapy, it is crucial to understand the mechanisms behind clonal evolution. Here, we applied single-cell transcriptomics and epigenomics, as well as whole-genome sequencing to 15 patients with relapsed/refractory multiple myeloma (RRMM). By profiling longitudinal samples throughout varying treatment regimens, we were able to interrogate patterns of evolution across patients. In particular, by defining clones based on copy number aberrations (CNAs), we found evidence for the majority of clones being diminished but not fully eradicated during treatment.","abstract":"Therapy resistance in cancers is ingrained in complex clonal dynamics. While the major clonal population in a tumour might respond well to the employed intervention, minor clones will eventually mutate, consequently acquiring a selective advantage and drug resistance. Hence, to improve cancer therapy, it is crucial to understand the mechanisms behind clonal evolution. Here, we applied single-cell transcriptomics and epigenomics, as well as whole-genome sequencing to 15 patients with relapsed/refractory multiple myeloma (RRMM). By profiling longitudinal samples throughout varying treatment regimens, we were able to interrogate patterns of evolution across patients. In particular, by defining clones based on copy number aberrations (CNAs), we found evidence for the majority of clones being diminished but not fully eradicated during treatment.","study_type":"Other","pubmed_ids":[37390336],"external_links":null,"is_released":true,"released_date":"2022-08-26T11:29:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006539","title":"cfDNA in Hereditary And High-Risk Malignancies (CHARM)","description":"Our goal is to improve early cancer detection by developing a blood test to predict cancer development in carriers using circulating DNA. As carriers develop cancer, they may have pre-cancerous cells which release this DNA into the blood (cell-free DNA; cfDNA), which can be detected with novel genetic technologies. We propose to use three complementary cfDNA assays:shallow whole genome sequencing (sWGS), Liquid-Biopsy Sequencing (LB-Seq) and Cell-free Methylated DNA Immunoprecipitation and High-throughput Sequencing (cfMeDip-Seq) for early cancer detection.","abstract":"Our goal is to improve early cancer detection by developing a blood test to predict cancer development in carriers using circulating DNA. As carriers develop cancer, they may have pre-cancerous cells which release this DNA into the blood (cell-free DNA; cfDNA), which can be detected with novel genetic technologies. We propose to use three complementary cfDNA assays:shallow whole genome sequencing (sWGS), Liquid-Biopsy Sequencing (LB-Seq) and Cell-free Methylated DNA Immunoprecipitation and High-throughput Sequencing (cfMeDip-Seq) for early cancer detection.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-26T19:23:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006540","title":"Robust methylation-based classification of brain tumours using nanopore sequencing","description":"Background: DNA methylation-based classification of cancer provides a comprehensive molecular approach to diagnose tumours. In fact, DNA methylation profiling of human brain tumours already profoundly impacts clinical neuro-oncology. However, current implementations using hybridization microarrays are time-consuming and costly. We recently reported on shallow nanopore whole-genome sequencing for rapid and cost-effective generation of genome-wide 5-methylcytosine profiles as input to supervised classification. Here, we demonstrate that this approach allows to discriminate a wide spectrum of primary brain tumours.\nResults: Using public reference data of 82 distinct tumour entities, we performed nanopore genome sequencing on N=382 tissue samples covering 46 brain tumour (sub)types. Using bootstrap sampling in a cohort of N = 56 cases, we find that a minimum set of 1,000 random CpG features is sufficient for high-confidence classification by ad hoc random forests. We implemented score recalibration as confidence measure for interpretation in a clinical context and empirically determined a platform-specific threshold in a randomly sampled discovery cohort (N = 185). Applying this cut-off to an independent validation series (N = 184) yielded 148 classifiable cases (sensitivity 80.4%) and demonstrated 100 % specificity. Cross-lab validation demonstrated robustness with concordant results across four laboratories in 10/11 (90.9%) cases. In a prospective benchmarking (N = 15), median time to results was 21.1 hours. \nConclusions: In conclusion, nanopore sequencing allows robust and rapid methylation-based classification across the full spectrum of brain tumours. Platform-specific confidence scores facilitate clinical implementation for which prospective evaluation is warranted and ongoing.","abstract":"Background: DNA methylation-based classification of cancer provides a comprehensive molecular approach to diagnose tumours. In fact, DNA methylation profiling of human brain tumours already profoundly impacts clinical neuro-oncology. However, current implementations using hybridization microarrays are time-consuming and costly. We recently reported on shallow nanopore whole-genome sequencing for rapid and cost-effective generation of genome-wide 5-methylcytosine profiles as input to supervised classification. Here, we demonstrate that this approach allows to discriminate a wide spectrum of primary brain tumours.\nResults: Using public reference data of 82 distinct tumour entities, we performed nanopore genome sequencing on N=382 tissue samples covering 46 brain tumour (sub)types. Using bootstrap sampling in a cohort of N = 56 cases, we find that a minimum set of 1,000 random CpG features is sufficient for high-confidence classification by ad hoc random forests. We implemented score recalibration as confidence measure for interpretation in a clinical context and empirically determined a platform-specific threshold in a randomly sampled discovery cohort (N = 185). Applying this cut-off to an independent validation series (N = 184) yielded 148 classifiable cases (sensitivity 80.4%) and demonstrated 100 % specificity. Cross-lab validation demonstrated robustness with concordant results across four laboratories in 10/11 (90.9%) cases. In a prospective benchmarking (N = 15), median time to results was 21.1 hours. \nConclusions: In conclusion, nanopore sequencing allows robust and rapid methylation-based classification across the full spectrum of brain tumours. Platform-specific confidence scores facilitate clinical implementation for which prospective evaluation is warranted and ongoing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-28T11:24:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006541","title":"Germline variants in patients with dual primary malignancies of the breast and lung","description":null,"abstract":"Multiple primary cancers (MPC) can occur in individuals due to an inherited predisposition. This study aimed to identify germline variants associated with dual primary cancers of the breast and lung.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006542","title":"Significant and pervasive effects of RNA degradation on Nanopore direct RNA sequencing","description":"Abstract \nOxford Nanopore direct RNA sequencing (DRS) is capable of sequencing complete RNA molecules and accurately measuring gene and isoform expression. However, as DRS is designed to profile intact RNA, expression quantification may be more heavily dependent upon RNA integrity than alternate RNA-seq methodologies. It is currently unclear how RNA degradation impacts DRS or if it can be corrected for. To assess the impact of RNA integrity on DRS we performed a degradation time-series using SH-SY5Y neuroblastoma cells. Our results demonstrate that degradation is a significant and pervasive factor that can bias DRS measurements, including a reduction in library complexity resulting in an overrepresentation of short genes and isoforms. Degradation also biases differential expression analyses; however, we find explicit correction can almost fully recover meaningful biological signal. In addition, DRS provided less biased profiling of partially degraded samples than nanopore cDNA-PCR sequencing. Overall, we find samples with RIN &gt; 9.5 can be treated as undegraded and samples with RIN &gt; 7 can be utilised for DRS with appropriate correction. These results establish the suitability of DRS for a wide range of samples, including partially degraded in-vivo clinical and post-mortem samples, whilst limiting the confounding effect of degradation on expression quantification.","abstract":"Abstract \nOxford Nanopore direct RNA sequencing (DRS) is capable of sequencing complete RNA molecules and accurately measuring gene and isoform expression. However, as DRS is designed to profile intact RNA, expression quantification may be more heavily dependent upon RNA integrity than alternate RNA-seq methodologies. It is currently unclear how RNA degradation impacts DRS or if it can be corrected for. To assess the impact of RNA integrity on DRS we performed a degradation time-series using SH-SY5Y neuroblastoma cells. Our results demonstrate that degradation is a significant and pervasive factor that can bias DRS measurements, including a reduction in library complexity resulting in an overrepresentation of short genes and isoforms. Degradation also biases differential expression analyses; however, we find explicit correction can almost fully recover meaningful biological signal. In addition, DRS provided less biased profiling of partially degraded samples than nanopore cDNA-PCR sequencing. Overall, we find samples with RIN &gt; 9.5 can be treated as undegraded and samples with RIN &gt; 7 can be utilised for DRS with appropriate correction. These results establish the suitability of DRS for a wide range of samples, including partially degraded in-vivo clinical and post-mortem samples, whilst limiting the confounding effect of degradation on expression quantification.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-29T05:33:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006543","title":"Creation and manipulation of genomic files","description":null,"abstract":"Creation and manipulation of all type of files used in a downstream analysis of genomic data (from fastq files to vcf files).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006544","title":"Nasal brushes part 1","description":null,"abstract":"Nasal Brushes scRNA-seq healthy and asthma pt 1","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006545","title":"Duplexseq_of_the_interstrand_crosslinks_WGS","description":"One of the most dangerous forms of DNA damage are interstrand crosslinks (ICLs), which covalently crosslink the two strands of the DNA double helix. The repair of these lesions is crucial for cellular survival due to their ability to block transcription and DNA replication. Initially, the major pathway that has been described in ICL repair involves a network of 22 genes that are mutated in a severe human genetic disease known as Fanconi Anemia (FA). \nUsing synthetic lethality screens in the near-haploid human HAP1 cell line, we recently identified two potentially novel regulators of ICL repair, C1orf112 and THAP12. Loss of C1orf112 and THAP12 causes hypersensitivity to ICL-inducing DNA damaging agents, such as Mitomycin C (MMC). Additionally, C1orf112-depleted cells show elevated levels of micronuclei and accumulation of DNA damage in S-phase. To better understand how C1orf112 and THAP12 mediate the repair of ICLs, we want to perform mutational signature analysis, using the BotSeq method. Therefore, WT, C1orf112 and THAP12 knockout cells were cultured in vehicle or MMC treated conditions for 10 days and the genomic DNA was isolated. FANCA and FANCD2 knockout cells are taken along as controls in this experimental setting.","abstract":"One of the most dangerous forms of DNA damage are interstrand crosslinks (ICLs), which covalently crosslink the two strands of the DNA double helix. The repair of these lesions is crucial for cellular survival due to their ability to block transcription and DNA replication. Initially, the major pathway that has been described in ICL repair involves a network of 22 genes that are mutated in a severe human genetic disease known as Fanconi Anemia (FA). \nUsing synthetic lethality screens in the near-haploid human HAP1 cell line, we recently identified two potentially novel regulators of ICL repair, C1orf112 and THAP12. Loss of C1orf112 and THAP12 causes hypersensitivity to ICL-inducing DNA damaging agents, such as Mitomycin C (MMC). Additionally, C1orf112-depleted cells show elevated levels of micronuclei and accumulation of DNA damage in S-phase. To better understand how C1orf112 and THAP12 mediate the repair of ICLs, we want to perform mutational signature analysis, using the BotSeq method. Therefore, WT, C1orf112 and THAP12 knockout cells were cultured in vehicle or MMC treated conditions for 10 days and the genomic DNA was isolated. FANCA and FANCD2 knockout cells are taken along as controls in this experimental setting.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-30T14:23:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006546","title":"Placenta_NanoSeq","description":"Whole-genome NanoSeq to assess the mutational processes that occur across pregnancies following different clinical courses.","abstract":"Whole-genome NanoSeq to assess the mutational processes that occur across pregnancies following different clinical courses.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006547","title":"A catalog of the genetic causes of Hereditary Angioedema in the Canary Islands (Spain)","description":"Hereditary angioedema (HAE) is a rare disease where known causes involve C1 inhibitor dysfunction or dysregulation of the kinin cascade. The updated HAE management guidelines recommend performing genetic tests to reach a precise diagnosis. Unfortunately, genetic tests are still uncommon in the diagnosis routine. Here, we characterized for the first time the genetic causes of HAE in affected families from the Canary Islands (Spain). Whole-exome sequencing data was obtained from 41 affected patients and unaffected relatives from 29 unrelated families identified in the archipelago. The Hereditary Angioedema Database Annotation (HADA) tool was used for pathogenicity classification and causal variant prioritization among the genes known to cause HAE. Manual reclassification of prioritized variants was used in those families lacking known causal variants. We detected a total of eight different variants causing HAE in this patient series, affecting essentially SERPING1 and F12 genes, one of them being a novel SERPING1 variant (c.686-12A&amp;gt;G) with a predicted splicing effect which was reclassified as likely pathogenic in one family. Altogether, the diagnostic yield by assessing previously reported causal genes and considering variant reclassifications according to the American College of Medical Genetics guidelines reached 66.7% (95% Confidence Interval [CI]: 30.1-91.0) in families with more than one affected member and 10.0% (95% CI: 1.8-33.1) among cases without family information for the disease. Despite the genetic causes of many patients remain to be identified, our results reinforce the need of genetic tests as first-tier diagnostic tool in this disease, as recommended by the international WAO/EAACI guidelines for the management of HAE.","abstract":"Hereditary angioedema (HAE) is a rare disease where known causes involve C1 inhibitor dysfunction or dysregulation of the kinin cascade. The updated HAE management guidelines recommend performing genetic tests to reach a precise diagnosis. Unfortunately, genetic tests are still uncommon in the diagnosis routine. Here, we characterized for the first time the genetic causes of HAE in affected families from the Canary Islands (Spain). Whole-exome sequencing data was obtained from 41 affected patients and unaffected relatives from 29 unrelated families identified in the archipelago. The Hereditary Angioedema Database Annotation (HADA) tool was used for pathogenicity classification and causal variant prioritization among the genes known to cause HAE. Manual reclassification of prioritized variants was used in those families lacking known causal variants. We detected a total of eight different variants causing HAE in this patient series, affecting essentially SERPING1 and F12 genes, one of them being a novel SERPING1 variant (c.686-12A&amp;gt;G) with a predicted splicing effect which was reclassified as likely pathogenic in one family. Altogether, the diagnostic yield by assessing previously reported causal genes and considering variant reclassifications according to the American College of Medical Genetics guidelines reached 66.7% (95% Confidence Interval [CI]: 30.1-91.0) in families with more than one affected member and 10.0% (95% CI: 1.8-33.1) among cases without family information for the disease. Despite the genetic causes of many patients remain to be identified, our results reinforce the need of genetic tests as first-tier diagnostic tool in this disease, as recommended by the international WAO/EAACI guidelines for the management of HAE.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-30T15:17:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006548","title":"Placenta_WES","description":"Examining the selective pressure underpinning mutagenesis in placentas.","abstract":"Examining the selective pressure underpinning mutagenesis in placentas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006549","title":"Oesophageal_Diseases_LCMWGS_","description":"Comprehensive clonal analysis of oesophageal diseases with an increased cancer risk using LCM-WGS.","abstract":"Oesophageal cancer is the 6th most common cause of cancer death worldwide with an overall 5 year survival of 10-25%. State of the art sequencing technologies have demonstrated that canonical driver mutations occur in normal tissues across organ types, challenging traditional understanding of clonal evolution in cancer development and presenting the opportunity to detect hidden genomic alterations in tissues with an increased cancer risk. This study aims to comprehensively identify the genomic alterations in benign oesophageal diseases with an increased cancer risk, including Chagas mega-oesophagus in 200 cases. Through combined duplex sequencing and Laser Capture Microdissection we aim to reconstruct the landscape of these diseases in unprecedented detail.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006550","title":"Base-resolution quantitative UV lesion footprinting by Capture CPD-seq reveals distinct damage signatures for DNA-binding proteins","description":null,"abstract":"Here, we expose cells or naked DNA to UV light followed by deep base-resolution quantification of the principal UV damage lesion, the cyclobutane pyrimidine dimer (CPD), at select human promoter regions using targeted CPD sequencing (Capture CPD-seq). This allowed per-base quantification of local stimulatory as well as inhibitory effects on UV damage formation. Our work reveals widespread and potent modulation of UV damage by proteins in regulatory regions while providing proof of principle for base-resolution study of protein-DNA interactions using light and sequencing.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006551","title":"Adult human kidney organoids originate from CD24+ cells and represent an advanced model for adult polycystic kidney disease","description":"Adult kidney organoids have been described as strictly tubular epithelial and termed tubuloids. While the cellular origin of tubuloids has remained elusive, here we report that they originate from a distinct CD24+ epithelial subpopulation. Long-term-cultured CD24+-derived tubuloids represent a functional human kidney tubule. We show that kidney tubuloids can be used to model the most common inherited kidney disease, namely autosomal dominant polycystic kidney disease (ADPKD), reconstituting the phenotypic hallmark of this disease with cyst formation. Single-cell RNA sequencing of CRISPR/Cas9 gene-edited PKD1 and PKD2 knockout tubuloids and human ADPKD and control tissue show similarities in upregulation of disease-driving genes. Furthermore, in a proof of concept, we demonstrate that tolvaptan, the only approved drug for ADPKD, shows a significant effect on cyst size in tubuloids but no effect in a pluripotent-stem-cell-derived model. Thus, tubuloids derive from a tubular epithelial subpopulation and represent an advanced model for ADPKD disease modeling.","abstract":"Adult kidney organoids have been described as strictly tubular epithelial and termed tubuloids. While the cellular origin of tubuloids has remained elusive, here we report that they originate from a distinct CD24+ epithelial subpopulation. Long-term-cultured CD24+-derived tubuloids represent a functional human kidney tubule. We show that kidney tubuloids can be used to model the most common inherited kidney disease, namely autosomal dominant polycystic kidney disease (ADPKD), reconstituting the phenotypic hallmark of this disease with cyst formation. Single-cell RNA sequencing of CRISPR/Cas9 gene-edited PKD1 and PKD2 knockout tubuloids and human ADPKD and control tissue show similarities in upregulation of disease-driving genes. Furthermore, in a proof of concept, we demonstrate that tolvaptan, the only approved drug for ADPKD, shows a significant effect on cyst size in tubuloids but no effect in a pluripotent-stem-cell-derived model. Thus, tubuloids derive from a tubular epithelial subpopulation and represent an advanced model for ADPKD disease modeling.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-08-31T16:11:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006552","title":"Synthetic genotypes and phenotypes of 500.000 individuals","description":"The goal of our study is to establish a pipeline for creating synthetic genotype and phenotype data on a Biobank scale. Such data can be used for developing new methodologies of analysis of common and rare diseases without risking de-identifying the underlying samples.","abstract":"The goal of our study is to establish a pipeline for creating synthetic genotype and phenotype data on a Biobank scale. Such data can be used for developing new methodologies of analysis of common and rare diseases without risking de-identifying the underlying samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-01T15:13:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006553","title":"Integrative modeling of tumor genomes and epigenomes for enhanced cancer diagnosis by cell-free DNA.","description":"3784 whole genome sequencing bam files were generated from plasma cell-free DNA of healthy individuals and patients with cancer. Paired reads were mapped to hg19 human reference genome.","abstract":"3784 whole genome sequencing bam files were generated from plasma cell-free DNA of healthy individuals and patients with cancer. Paired reads were mapped to hg19 human reference genome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-01T16:50:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006554","title":"A living biobank of patient-derived ductal carcinoma in situ Mouse-INtraDuctal xenografts identifies factors associated with risk of invasive progression","description":"Create a living biobank of patient-derived ductal carcinoma in situ (DCIS) Mouse-INtraDuctal (MIND) xenografts to find factors explaining invasive growth. Samples exist of both primary and pdx samples. Invasive growth was scored in the pdx.","abstract":"Create a living biobank of patient-derived ductal carcinoma in situ (DCIS) Mouse-INtraDuctal (MIND) xenografts to find factors explaining invasive growth. Samples exist of both primary and pdx samples. Invasive growth was scored in the pdx.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-02T08:03:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006555","title":"Ovarian carcinosarcoma genomics and eribulin response","description":"Ovarian carcinosarcoma (OCS) is an aggressive and rare tumour type with limited treatment options. OCS is hypothesised to develop via the combination theory, with a single progenitor resulting in carcinomatous and sarcomatous components, or alternatively via the conversion theory, with the sarcomatous component developing from the carcinomatous component through epithelial-to-mesenchymal transition (EMT). In this study, we analysed DNA variants from isolated carcinoma and sarcoma components to show that OCS from 18 women is monoclonal. RNA sequencing indicated the carcinoma components were more mesenchymal when compared with pure epithelial ovarian carcinomas, supporting the conversion theory and suggesting that EMT is important in the formation of these tumours.","abstract":"Ovarian carcinosarcoma (OCS) is an aggressive and rare tumour type with limited treatment options. OCS is hypothesised to develop via the combination theory, with a single progenitor resulting in carcinomatous and sarcomatous components, or alternatively via the conversion theory, with the sarcomatous component developing from the carcinomatous component through epithelial-to-mesenchymal transition (EMT). In this study, we analysed DNA variants from isolated carcinoma and sarcoma components to show that OCS from 18 women is monoclonal. RNA sequencing indicated the carcinoma components were more mesenchymal when compared with pure epithelial ovarian carcinomas, supporting the conversion theory and suggesting that EMT is important in the formation of these tumours.","study_type":"Other","pubmed_ids":[36206301],"external_links":null,"is_released":true,"released_date":"2022-09-05T05:56:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006556","title":"Datasetarnau2","description":null,"abstract":"Test the submission of more that 1 dataset","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006557","title":"Sequencing Data of HGSC patient-derived cell lines and organoids","description":null,"abstract":"Sequencing data of HGSC patient-derived cell lines and organoids, and possible fresh frozen tumor samples from same patients.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-05T12:55:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006558","title":"H3Africa - Kidney Disease Research Network","description":"Chronic kidney disease (CKD) affects an estimated 14% of adults in sub-Saharan Africa but very little research has been done on the etiology, progression and prevention of CKD on the continent. As part of the Human Heredity and Health in Africa (H3A) Consortium, the H3Africa Kidney Disease Research Network was established to study prevalent forms of kidney disease in sub-Saharan Africa and increase the capacity for genetics and genomics research. The study is performing comprehensive phenotypic characterization with analysis of environmental and genetic factors from seven clinical centers in two African countries (Ghana and Nigeria) over a five-year period. Approximately 4,000 participants with specified kidney disease diagnoses and 4000 control participants will be enrolled in the four African countries. In addition, approximately 50 families with hereditary glomerular disease will be enrolled. The study includes both pediatric and adult participants ages &lt;1 to 74yrs across a broad spectrum of kidney diseases secondary to hypertension, diabetes, human immunodeficiency virus, sickle cell disease, biopsy-proven glomerular disease and CKD of unknown origin. Clinical and demographic data with biospecimens are collected for assessment of clinical, biochemical and genetic markers of kidney disease.","abstract":"Chronic kidney disease (CKD) affects an estimated 14% of adults in sub-Saharan Africa but very little research has been done on the etiology, progression and prevention of CKD on the continent. As part of the Human Heredity and Health in Africa (H3A) Consortium, the H3Africa Kidney Disease Research Network was established to study prevalent forms of kidney disease in sub-Saharan Africa and increase the capacity for genetics and genomics research. The study is performing comprehensive phenotypic characterization with analysis of environmental and genetic factors from seven clinical centers in two African countries (Ghana and Nigeria) over a five-year period. Approximately 4,000 participants with specified kidney disease diagnoses and 4000 control participants will be enrolled in the four African countries. In addition, approximately 50 families with hereditary glomerular disease will be enrolled. The study includes both pediatric and adult participants ages &lt;1 to 74yrs across a broad spectrum of kidney diseases secondary to hypertension, diabetes, human immunodeficiency virus, sickle cell disease, biopsy-proven glomerular disease and CKD of unknown origin. Clinical and demographic data with biospecimens are collected for assessment of clinical, biochemical and genetic markers of kidney disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-05T13:25:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006559","title":"Single-cell ATAC-seq analysis for COVID19 patients","description":"While SARS-CoV-2 infection causes mild respiratory disease in most individuals, a small group of patients develops severe COVID-19. Dysfunctional innate immune responses have been identified to contribute to differences in COVID-19 severity, but the key regulators are still unknown. Here, we present an integrative single-cell epigenetics, transcriptomic, and genetics analysis of peripheral blood mononuclear cells from hospitalized and convalescent COVID-19 patients. In classical monocytes, we identified 41.3% of significantly up-regulated genes in hospitalized COVID-19 patients potentially induced by differential chromatin accessibility. Sub-clustering and motif-enrichment analyses of monocytes reveal disease condition-specific regulation by transcription factors, such as C/EBPs and SPI1, and their targets, including a long-noncoding RNA LUCAT1, which further regulates interferon responses and is associated with the need for oxygen supply of COVID-19 patients. The interaction between C/EBPs and LUCAT1 was validated through loss-of-function experiments. Finally, we investigated genetic risk variants that exhibit allele-specific open chromatin (ASoC) in promoters/enhancers of COVID-19 patients. Integrating our data with publicly available expression quantitative trait loci and chromosomal interactions indicates that ASoC SNP rs6800484-C is associated with lower expression of CCR2, which may contributeto higher viral loads in lungs and higher risk of COVID-19 hospitalization. Altogether, our study highlights the diverse genetic and epigenetic regulators that contribute to the innate immune responses of different COVID-19 patients.","abstract":"While SARS-CoV-2 infection causes mild respiratory disease in most individuals, a small group of patients develops severe COVID-19. Dysfunctional innate immune responses have been identified to contribute to differences in COVID-19 severity, but the key regulators are still unknown. Here, we present an integrative single-cell epigenetics, transcriptomic, and genetics analysis of peripheral blood mononuclear cells from hospitalized and convalescent COVID-19 patients. In classical monocytes, we identified 41.3% of significantly up-regulated genes in hospitalized COVID-19 patients potentially induced by differential chromatin accessibility. Sub-clustering and motif-enrichment analyses of monocytes reveal disease condition-specific regulation by transcription factors, such as C/EBPs and SPI1, and their targets, including a long-noncoding RNA LUCAT1, which further regulates interferon responses and is associated with the need for oxygen supply of COVID-19 patients. The interaction between C/EBPs and LUCAT1 was validated through loss-of-function experiments. Finally, we investigated genetic risk variants that exhibit allele-specific open chromatin (ASoC) in promoters/enhancers of COVID-19 patients. Integrating our data with publicly available expression quantitative trait loci and chromosomal interactions indicates that ASoC SNP rs6800484-C is associated with lower expression of CCR2, which may contributeto higher viral loads in lungs and higher risk of COVID-19 hospitalization. Altogether, our study highlights the diverse genetic and epigenetic regulators that contribute to the innate immune responses of different COVID-19 patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-05T13:58:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006560","title":"Single-cell RNA-seq analysis for COVID19 patients","description":"While SARS-CoV-2 infection causes mild respiratory disease in most individuals, a small group of patients develops severe COVID-19. Dysfunctional innate immune responses have been identified to contribute to differences in COVID-19 severity, but the key regulators are still unknown. Here, we present an integrative single-cell epigenetics, transcriptomic, and genetics analysis of peripheral blood mononuclear cells from hospitalized and convalescent COVID-19 patients. In classical monocytes, we identified 41.3% of significantly up-regulated genes in hospitalized COVID-19 patients potentially induced by differential chromatin accessibility. Sub-clustering and motif-enrichment analyses of monocytes reveal disease condition-specific regulation by transcription factors, such as C/EBPs and SPI1, and their targets, including a long-noncoding RNA LUCAT1, which further regulates interferon responses and is associated with the need for oxygen supply of COVID-19 patients. The interaction between C/EBPs and LUCAT1 was validated through loss-of-function experiments. Finally, we investigated genetic risk variants that exhibit allele-specific open chromatin (ASoC) in promoters/enhancers of COVID-19 patients. Integrating our data with publicly available expression quantitative trait loci and chromosomal interactions indicates that ASoC SNP rs6800484-C is associated with lower expression of CCR2, which may contributeto higher viral loads in lungs and higher risk of COVID-19 hospitalization. Altogether, our study highlights the diverse genetic and epigenetic regulators that contribute to the innate immune responses of different COVID-19 patients.","abstract":"While SARS-CoV-2 infection causes mild respiratory disease in most individuals, a small group of patients develops severe COVID-19. Dysfunctional innate immune responses have been identified to contribute to differences in COVID-19 severity, but the key regulators are still unknown. Here, we present an integrative single-cell epigenetics, transcriptomic, and genetics analysis of peripheral blood mononuclear cells from hospitalized and convalescent COVID-19 patients. In classical monocytes, we identified 41.3% of significantly up-regulated genes in hospitalized COVID-19 patients potentially induced by differential chromatin accessibility. Sub-clustering and motif-enrichment analyses of monocytes reveal disease condition-specific regulation by transcription factors, such as C/EBPs and SPI1, and their targets, including a long-noncoding RNA LUCAT1, which further regulates interferon responses and is associated with the need for oxygen supply of COVID-19 patients. The interaction between C/EBPs and LUCAT1 was validated through loss-of-function experiments. Finally, we investigated genetic risk variants that exhibit allele-specific open chromatin (ASoC) in promoters/enhancers of COVID-19 patients. Integrating our data with publicly available expression quantitative trait loci and chromosomal interactions indicates that ASoC SNP rs6800484-C is associated with lower expression of CCR2, which may contributeto higher viral loads in lungs and higher risk of COVID-19 hospitalization. Altogether, our study highlights the diverse genetic and epigenetic regulators that contribute to the innate immune responses of different COVID-19 patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-05T13:58:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006561","title":"Mechanisms of duodenal adenoma development in familial polyposis syndromes","description":null,"abstract":"Duodenal polyposis is an important cause of morbidity and mortality in the inherited tumour syndromes Familial Adenomatous Polyposis (FAP) and MUTYH-associated Polyposis (MAP), yet this process remains poorly understood. This study aimed to identify genes that are mutated in FAP and MAP duodenal adenomas and their cellular consequences for duodenal tumorigenesis. Whole exome and whole transcriptome sequencing of 70 duodenal adenomas from patients with FAP and MAP identified putative drivers of duodenal tumorigenesis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006562","title":"The effect of the 7R allele on the DRD4 risk tolerance locus is independent of background risk in Senegalese fishermen","description":null,"abstract":"It has been shown that living in risky environments, as well as having a risky occupation, can moderate risk-tolerance. Despite the involvement of dopamine in the expectation of reward described by neurobiologists, a GWAS study was not able to demonstrate a genetic contribution of genes involved in the dopaminergic pathway in risk attitudes and gene candidate studies gave contrasting results. We test the possibility that a genetic effect of the DRD4-7R allele in risk-taking behavior could be modulated by environmental factors. We show that the increase in risk-tolerance due to the 7R allele is independent of the environmental risk in two populations in Northern Senegal, one of which is exposed to a very high risk due to dangerous fishing.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006563","title":"Single cell transcriptome profiling of childhood soft tissue sarcomas","description":"Single cell transcriptome profiling of childhood soft tissue sarcomas","abstract":"Single cell transcriptome profiling of childhood soft tissue sarcomas","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-05T16:42:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006564","title":"Circulating miRNA profiling","description":null,"abstract":"A number of studies have demonstrated a key role of miRNA isolated from cells as disease-specific biomarkers of autoimmune rheumatic disease. \n\nCirculating miRNA-19b can be a biomarker of disease progression and treatment response to baricitinib in rheumatoid arthritis patients through miRNA profiling of monocytes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006565","title":"Hematopoietic differentiation at single-cell resolution in NPM1-mutated AML","description":"To investigate the relationship between somatic mutations and phenotypic hematologic differentiation at the single-cell level, we used a droplet-based multi-omics single-cell platform on eleven NPM1-mutated AML diagnostic samples. We developed a bioinformatics framework to perform phylogeny-driven genotype correction, that allowed us to study 52 103 single cells. Intra-leukemic genetic heterogeneity was detectable in all patients, including a branched architecture in nine of them, always owing to co-occurring signaling mutations. We identified two groups of NPM1-mutated AML, one characterized by a progenitor immunophenotype and a second one with a predominant monocytic differentiation. We also identified various degrees of intra-leukemic immunophenotype heterogeneity, sometimes associated with strong genetic/phenotype correlations.","abstract":"To investigate the relationship between somatic mutations and phenotypic hematologic differentiation at the single-cell level, we used a droplet-based multi-omics single-cell platform on eleven NPM1-mutated AML diagnostic samples. We developed a bioinformatics framework to perform phylogeny-driven genotype correction, that allowed us to study 52 103 single cells. Intra-leukemic genetic heterogeneity was detectable in all patients, including a branched architecture in nine of them, always owing to co-occurring signaling mutations. We identified two groups of NPM1-mutated AML, one characterized by a progenitor immunophenotype and a second one with a predominant monocytic differentiation. We also identified various degrees of intra-leukemic immunophenotype heterogeneity, sometimes associated with strong genetic/phenotype correlations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-05T19:10:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006566","title":"Oesophageal_Diseases_Dupseq","description":"Comprehensive clonal analysis of oesopahgeal diseases with an increased cancer risk using Dup-Seq","abstract":"Oesophageal cancer is the 6th most common cause of cancer death worldwide with an overall 5 year survival of 10-25%. State of the art sequencing technologies have demonstrated that canonical driver mutations occur in normal tissues across organ types, challenging traditional understanding of clonal evolution in cancer development and presenting the opportunity to detect hidden genomic alterations in tissues with an increased cancer risk. This study aims to comprehensively identify the genomic alterations in benign oesophageal diseases with an increased cancer risk, including Chagas mega-oesophagus in 200 cases. Through combined duplex sequencing and Laser Capture Microdissection we aim to reconstruct the landscape of these diseases in unprecedented detail.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006567","title":"Deciphering somatic mosaic structural variation in human blood lineages using single-cell multiomics","description":"Somatic mosaicism (SM), referring to the presence of somatic mutations in sub-populations of cells within healthy individuals, is associated with an increased risk of a variety of diseases, including cancer. Blood is at particularly high risk of SM, given its rapid turnover and functionally- heterogeneous cell-type composition. While the roles of point mutations and large-scale rearrangements in blood SM have been scrutinised in recent years, the functional impact of mosaic structural variants (mSVs) remains poorly understood.\nUsing haplotype-resolved single-cell multi-omics, we explored the mSV landscape of human hematopoietic stem and progenitor cells (HSPCs).","abstract":"Somatic mosaicism (SM), referring to the presence of somatic mutations in sub-populations of cells within healthy individuals, is associated with an increased risk of a variety of diseases, including cancer. Blood is at particularly high risk of SM, given its rapid turnover and functionally- heterogeneous cell-type composition. While the roles of point mutations and large-scale rearrangements in blood SM have been scrutinised in recent years, the functional impact of mosaic structural variants (mSVs) remains poorly understood.\nUsing haplotype-resolved single-cell multi-omics, we explored the mSV landscape of human hematopoietic stem and progenitor cells (HSPCs).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-06T12:51:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006568","title":"Single-cell transcriptome landscape of developing fetal gonads defines somatic cell lineage specification in humans","description":"We present the comprehensive transcriptional dynamics of cell types populating the male and female developing gonads at a single-cell level. We recovered the gene expression programs of around 128,000 single cells derived from 17 fetal testes and 16 fetal ovaries from 5 to 12 postconceptional weeks. The resulting dataset provides an unprecedented overview of this key period in sex determination and gonadal development.","abstract":"We present the comprehensive transcriptional dynamics of cell types populating the male and female developing gonads at a single-cell level. We recovered the gene expression programs of around 128,000 single cells derived from 17 fetal testes and 16 fetal ovaries from 5 to 12 postconceptional weeks. The resulting dataset provides an unprecedented overview of this key period in sex determination and gonadal development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-06T13:56:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006569","title":"scRNA-seq analysis of human fetal gonads and mesonephroi, first trimester","description":null,"abstract":"The goal of this study is to understand the cellular events underlying the early differentiation of the human fetal genital tract. For this purpose, we captured and sequenced cells from gonads and/or mesonephroi between 5 and 12 postconceptional weeks (PCW) using the 10x Genomics Chromium™ Single Cell 3' RNA analysis solution. These include five individuals (gonads + mesonephroi) at 5 PCW and 19 individuals (mesonephroi only) from 6 to 12 PCW.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006570","title":"scRNA-seq analysis of DHH-manipulated human fetal testes","description":null,"abstract":"The goal of this study is to understand how the differentiation of testicular cell lineages is affected when manipulating the DHH signaling pathway. For this purpose, we captured and sequenced cells from 7 postconceptional weeks human fetal testes (N=4 individuals) after organotypic cultures with known receptor agonist (SAG), antagonist (cyclopamine), or in control conditions (DMSO) using the 10x Genomics Chromium™ Single Cell 3' RNA analysis solution.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006571","title":"scRNA-seq analysis of ibuprofen-treated human fetal gonads","description":null,"abstract":"The goal of this study is to identify the cellular targets of Ibuprofen in human fetal gonads and the corresponding altered gene pathways. Manipulations were performed during organotypic cultures of 8-10 postconceptional weeks (PCW) testes (N=3 individuals) and 10-12 PCW ovaries (N=3 individuals), and the scRNA-seq experiments were performed using the 10x Genomics Chromium™ Single Cell 3' RNA analysis solution.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006572","title":"HSC_colony_many_years_post_allogeneic_bone_marrow_transplant___Bait_set_3","description":"This study looks at human donors and recipients of allogeneic blood &amp; marrow marrow transplantation. Each transplant \"pair\" (donor &amp; recipient) underwent the transplant procedure 10 -30 years prior to sampling - the majority for an underlying diagnosis of leukemia.  We will perform whole-genome sequencing on tens to hundreds of single HSPC (haematopoietic stem and progenitor cell)-derived colonies per individual. We will infer the phylogeny of these cells (those from both donor &amp; recipient within a pair) by analysing the somatically acquired mutations within each cell. The structure of the phylogeny will allow estimates of hitherto unknown parameters such as the number of HSCs that engraft long-term, the dynamics of the engraftment process on the HSC level, and the additional mutation burden acquired through the arduous transplant procedure.\nThis TGS part of the study is used for assessing the contribution of clones to mature blood subsets, and better timing mutations relative to transplantation.","abstract":"We propose the use of whole genome sequencing, along with state-of-the-art phylogenetic methods, to reconstruct the dynamics of stem cell engraftment in patients undergoing allogeneic stem cell transplantation for haematological disease:\n\t\n-\tHow many infused haematopoietic stem cells successfully engraft and contribute to subsequent haematopoiesis in human recipients?\n-\tWhat is the time course and phylogenetic structure of stem cell reconstitution?\n-\tAre the outputs of individual engrafting stem_cells biased towards particular lineages e.g. myeloid vs B/T lymphoid?\n\nWithin our study cohort we anticipate a variety of recipient/ donor characteristics, conditioning regimens (myeloablative or reduced-intensity) and other transplant variables (e.g. transplanted cell dose).  Although this study will not have statistical power to draw definitive conclusions on how these differences affect transplant phylodynamics it will establish proof of principle for this type of analysis and inform hypotheses for future studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-06T14:28:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006573","title":"Longitudinal monitoring of cell-free DNA methylation in ALK-positive non-small cell lung cancer patients","description":"Here, we performed genome-wide 5-mC profiling in plasma of metastatic ALK-rearranged non-small cell lung cancer (NSCLC) patients receiving tyrosine kinase inhibitor therapy. We established a strategy to identify ALK-specific 5-mC changes from cfDNA and demonstrated the suitability of the identified markers for cancer detection, prognosis and therapy monitoring. Longitudinal plasma samples (n = 79) of 21 ALK-positive NSCLC patients and 13 healthy donors were collected alongside 15 ALK-positive tumor tissue and 10 healthy lung tissue specimens. All plasma and tissue samples were analyzed by cell-free DNA methylation immunoprecipitation sequencing to generate genome-wide 5-mC profiles. Information on genomic alterations (i.e., somatic mutations/fusions and copy number alterations) determined in matched plasma samples were available from previous studies.","abstract":"Here, we performed genome-wide 5-mC profiling in plasma of metastatic ALK-rearranged non-small cell lung cancer (NSCLC) patients receiving tyrosine kinase inhibitor therapy. We established a strategy to identify ALK-specific 5-mC changes from cfDNA and demonstrated the suitability of the identified markers for cancer detection, prognosis and therapy monitoring. Longitudinal plasma samples (n = 79) of 21 ALK-positive NSCLC patients and 13 healthy donors were collected alongside 15 ALK-positive tumor tissue and 10 healthy lung tissue specimens. All plasma and tissue samples were analyzed by cell-free DNA methylation immunoprecipitation sequencing to generate genome-wide 5-mC profiles. Information on genomic alterations (i.e., somatic mutations/fusions and copy number alterations) determined in matched plasma samples were available from previous studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-06T15:33:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006574","title":"Erasmus MC COVID-19 cohort-associated connected datasets study","description":null,"abstract":"As part of a multidisciplinary consortium (https://recodid.eu/), the study aims at connecting clinical-epidemiological (CE) data with further datasets from research on many other aspects of SARS-CoV-2. This study includes CE data for a cohort of 151 PCR-confirmed COVID-19 individuals from a group of 273 patients who were admitted to the hospital with a respiratory infection or respiratory failure in 2020-2021.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-06T16:53:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006575","title":"Whole-genome sequencing in gastric cancer (part2)","description":"we analysis structural variations (SVs) and mutational signatures via whole-genome sequencing of 168 GCs. Our data demonstrates diverse models of complex SVs operative in GC, which lead to high-level amplification of oncogenes. We find varying proportion of tandem-duplications (TDs) among individuals and identify 24 TD hotspots involving well-established cancer genes such as CCND1, ERBB2 and MYC.","abstract":"we analysis structural variations (SVs) and mutational signatures via whole-genome sequencing of 168 GCs. Our data demonstrates diverse models of complex SVs operative in GC, which lead to high-level amplification of oncogenes. We find varying proportion of tandem-duplications (TDs) among individuals and identify 24 TD hotspots involving well-established cancer genes such as CCND1, ERBB2 and MYC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-07T04:35:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006576","title":"Long-read sequencing of diagnosis and post-therapy medulloblastoma reveals complex rearrangement patterns and epigenetic signatures","description":"Cancer genomes harbor a broad spectrum of structural variants (SV) driving tumorigenesis, a relevant subset of which are likely to escape discovery in short reads. We employed Oxford Nanopore Technologies (ONT) sequencing in a paired diagnostic and post-therapy medulloblastoma to unravel the haplotype-resolved somatic genetic and epigenetic landscape. We assemble complex rearrangements and such associated with telomeric sequences, including a 1.55 Megabasepair chromothripsis event. We uncover a complex SV pattern termed \"templated insertion thread\", characterized by short (mostly less than 1kb) insertions showing prevalent self-concatenation into highly amplified structures of up to 50kbp in size. Templated insertion threads occur in 3% of cancers, with a prevalence ranging to 74% in liposarcoma, and frequent colocalization with chromothripsis. We also perform long-read based methylome profiling and discover allele-specific methylation (ASM) effects, complex rearrangements exhibiting differential methylation, and differential promoter methylation in seven cancer-driver genes. Our study shows the potential of long-read sequencing in cancer.","abstract":"Cancer genomes harbor a broad spectrum of structural variants (SV) driving tumorigenesis, a relevant subset of which are likely to escape discovery in short reads. We employed Oxford Nanopore Technologies (ONT) sequencing in a paired diagnostic and post-therapy medulloblastoma to unravel the haplotype-resolved somatic genetic and epigenetic landscape. We assemble complex rearrangements and such associated with telomeric sequences, including a 1.55 Megabasepair chromothripsis event. We uncover a complex SV pattern termed \"templated insertion thread\", characterized by short (mostly less than 1kb) insertions showing prevalent self-concatenation into highly amplified structures of up to 50kbp in size. Templated insertion threads occur in 3% of cancers, with a prevalence ranging to 74% in liposarcoma, and frequent colocalization with chromothripsis. We also perform long-read based methylome profiling and discover allele-specific methylation (ASM) effects, complex rearrangements exhibiting differential methylation, and differential promoter methylation in seven cancer-driver genes. Our study shows the potential of long-read sequencing in cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-07T15:46:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006577","title":"The genomic landscape of acute lymphoblastic leukemia with intrachromosomal amplification of chromosome 21","description":"Use scRNA-seq data from 4 iAMP21 patients to study the clonal evolution of iAMP21.","abstract":"Use scRNA-seq data from 4 iAMP21 patients to study the clonal evolution of iAMP21.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-07T22:05:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006578","title":"Transcriptomic profiles of chronic lymphocytic leukemia before and after frontline therapy: 5-year results from the randomized CLL14 study","description":null,"abstract":"BCL2 inhibition by venetoclax has become one of the backbones in the treatment of chronic lymphocytic leukemia (CLL). While high rates of undetectable minimal residual disease (uMRD) have been observed at the end of venetoclax-combination therapies, the biological drivers of response or non-response have so far not been elucidated. Furthermore, long-term clinical outcomes of patients after venetoclax exposure are still limited.\nIn this randomized study, patients with previously untreated CLL received either 1-year venetoclax-obinutuzumab (Ven-Obi) or chlorambucil-Obi (Clb-Obi) therapy (NCT02242942). The primary endpoint of the study was investigator-assessed progression-free survival (PFS) and secondary endpoints included MRD by next generation sequencing and overall survival. CD19-enriched blood from patients before therapy and at relapse was subjected to RNA sequencing (RNAseq) for exploratory analyses.\nAfter a median follow-up of 65.4 months (interquartile range 52.6-69.4), PFS was significantly superior for Ven-Obi compared to Clb-Obi (median not reached [nr] vs 36.4 months; hazard ratio [HR] 0.35 [95% CI 0.26-0.46], p&lt;0.0001). At 5 years after randomization, the estimated PFS rate was 62.6% after Ven-Obi and 27.0% after Clb-Obi. Multivariable analyses indicated deletion 17p and lymph node size ≥5 cm as independent adverse prognostic factors for PFS in patients treated with Ven-Obi, and unmutated IGHV status, deletion 17p, deletion 11q, complex karyotype and lymph node size ≥5cm in patients treated with Clb-Obi.\nPatients with MRD6 (&lt;10-6) had a significantly longer PFS than pts who had MRD4 (&lt;10-4, ≥10-5) or MRD+ (≥10-4), but not MRD5 (&lt;10-5, ≥10-6). MRD+ status was associated with increased expression of multi-drug resistance gene ABCB1, whereas MRD6 was associated with BCL2L11 (BIM) expression. Inflammatory response pathways, including upregulation of IL2RB, LCP2 and BST2 genes, were enriched in MRD+ patients, suggesting a role in impaired response to BCL2 inhibition.\nThese data indicate sustained long-term efficacy of fixed-duration Ven-Obi in patients with previously untreated CLL that is based on potent MRD reduction. The distinct transcriptomic profile of non-responders suggests possible biological vulnerabilities that could be leveraged to improve treatment efficacy and outcomes.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006579","title":"Collection_and_QC_study_only","description":"Collection and QC study only","abstract":"Collection and QC study only","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006580","title":"Whole_Genome_Methylation_sequencing_of_colonies_from_monozygotic_twins_with_hereditary_spherocytosis","description":"Whole Genome methylation analysis of colonies from monozygotic twins with hereditary spherocytosis.","abstract":"Whole Genome methylation analysis of colonies from monozygotic twins with hereditary spherocytosis.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006581","title":"Whole_Genome_Methylation_sequencing_of_CML_colonies","description":"Whole Genome methylation analysis of CML colonies","abstract":"Whole Genome methylation analysis of CML colonies","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006582","title":"Whole transcriptome profiling of liquid biopsies from tumour xenografted mouse models: validation cohort","description":"While cell-free DNA (cfDNA) in liquid biopsies is widely being used and investigated, free circulating RNA (extracellular RNA, exRNA) has the potential to improve therapy response monitoring and cancer detection due to its dynamic nature. A fundamental open question hampering the initiation of large-scale liquid biopsy collections for tumour exRNA analysis is that it remains unclear in which blood subcompartment tumour-derived exRNAs primarily reside. We set out to develop a host-xenograft deconvolution framework, exRNAxeno, with cDNA mapping strategies to either a combined human-mouse reference genome or both species genomes in parallel, that can be applied to exRNA sequencing data from liquid biopsies of human xenograft mouse models, enabling to distinguish (human) tumoural RNA from (murine) host RNA, and as such to specifically analyse tumour-derived exRNA. Subsequently, the preferred exRNAxeno combination pipeline was applied to total exRNA sequencing data from blood platelets and three plasma fractions from a breast cancer patient-derived and neuroblastoma cell line-derived xenograft mouse model. We show that tumoural exRNA concentrations are not determined by plasma platelet levels, while host exRNA concentrations increase with platelet content. Furthermore, a large variability in exRNA levels and gene content across individual mice is observed. In general, the tumoural gene detectability in plasma is correlated with the RNA expression levels in the tumour tissue or cancer cell line. Our results unravel new aspects of tumour-derived exRNA biology in xenograft mouse models.","abstract":"While cell-free DNA (cfDNA) in liquid biopsies is widely being used and investigated, free circulating RNA (extracellular RNA, exRNA) has the potential to improve therapy response monitoring and cancer detection due to its dynamic nature. A fundamental open question hampering the initiation of large-scale liquid biopsy collections for tumour exRNA analysis is that it remains unclear in which blood subcompartment tumour-derived exRNAs primarily reside. We set out to develop a host-xenograft deconvolution framework, exRNAxeno, with cDNA mapping strategies to either a combined human-mouse reference genome or both species genomes in parallel, that can be applied to exRNA sequencing data from liquid biopsies of human xenograft mouse models, enabling to distinguish (human) tumoural RNA from (murine) host RNA, and as such to specifically analyse tumour-derived exRNA. Subsequently, the preferred exRNAxeno combination pipeline was applied to total exRNA sequencing data from blood platelets and three plasma fractions from a breast cancer patient-derived and neuroblastoma cell line-derived xenograft mouse model. We show that tumoural exRNA concentrations are not determined by plasma platelet levels, while host exRNA concentrations increase with platelet content. Furthermore, a large variability in exRNA levels and gene content across individual mice is observed. In general, the tumoural gene detectability in plasma is correlated with the RNA expression levels in the tumour tissue or cancer cell line. Our results unravel new aspects of tumour-derived exRNA biology in xenograft mouse models.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-08T11:51:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006583","title":"RNAseq of liver harvested from CDAHFD mice treated for 8 weeks with either the MGAT2 inhibitor compound BMS-963272 or vehicle","description":"This experiment consists of RNAseq of liver harvested from CDAHFD mice treated for 8 weeks with either the MGAT2 inhibitor compound BMS-963272 (N = 10) or with vehicle (N = 10).","abstract":"This experiment consists of RNAseq of liver harvested from CDAHFD mice treated for 8 weeks with either the MGAT2 inhibitor compound BMS-963272 (N = 10) or with vehicle (N = 10).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-08T19:37:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006584","title":"RNAseq of jejunum (small intestine) harvested from CDAHFD mice treated for 8 weeks with either the MGAT2 inhibitor compound BMS-963272 or vehicle","description":"This experiment consists of RNAseq of jejunum (small intestine) harvested from CDAHFD mice treated for 8 weeks with either the MGAT2 inhibitor compound BMS-963272 (N = 14) or with vehicle (N = 14).","abstract":"This experiment consists of RNAseq of jejunum (small intestine) harvested from CDAHFD mice treated for 8 weeks with either the MGAT2 inhibitor compound BMS-963272 (N = 14) or with vehicle (N = 14).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-08T20:11:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006585","title":"Somatic mutations predict an aggressive phenotype in meningioma but do not drive grade progression","description":"A subset of meningiomas progress in histopathological grade and drivers of progression are poorly understood. We aimed to identify somatic mutations and copy number alterations (CNAs) associated with grade progression in a unique matched tumour dataset.\nUtilising a prospective database, we identified 10 patients with meningiomas that had undergone grade progression and for whom matched pre- and post-progression tissue (n=50 samples) was available for targeted next-generation sequencing.\nMutations in NF2 were identified in 4/10 patients, 94% were non-skull base tumours. In one patient, three different NF2 mutations were identified in four tumours. NF2 mutated tumours showed large scale CNAs, with highly recurrent losses in 1p, 10, 22q, and frequent CNAs on chromosomes 2, 3 and 4. There was a correlation between grade and CNAs in a subset of patients. In two patients with sphenoid wing Grade III tumours without detected NF2 mutations, a STAT6-NAB2 inversion was identified. Two patients with tumours without detected NF2 mutations showed a combination of loss and high gain on chromosome 17q. Mutations in SETD2, TP53, TERT promoter and NF2 were not uniform across recurrent tumours and did not correspond with grade progression.\nMeningiomas that progress in grade generally have a mutational profile already detectable in the pre-progressed tumour, suggesting an aggressive phenotype . CNA profiling shows frequent alterations in NF2 mutated tumours compared to non NF2 mutated tumours and the pattern of CNAs may be associated with grade progression in a subset of cases.","abstract":"A subset of meningiomas progress in histopathological grade and drivers of progression are poorly understood. We aimed to identify somatic mutations and copy number alterations (CNAs) associated with grade progression in a unique matched tumour dataset.\nUtilising a prospective database, we identified 10 patients with meningiomas that had undergone grade progression and for whom matched pre- and post-progression tissue (n=50 samples) was available for targeted next-generation sequencing.\nMutations in NF2 were identified in 4/10 patients, 94% were non-skull base tumours. In one patient, three different NF2 mutations were identified in four tumours. NF2 mutated tumours showed large scale CNAs, with highly recurrent losses in 1p, 10, 22q, and frequent CNAs on chromosomes 2, 3 and 4. There was a correlation between grade and CNAs in a subset of patients. In two patients with sphenoid wing Grade III tumours without detected NF2 mutations, a STAT6-NAB2 inversion was identified. Two patients with tumours without detected NF2 mutations showed a combination of loss and high gain on chromosome 17q. Mutations in SETD2, TP53, TERT promoter and NF2 were not uniform across recurrent tumours and did not correspond with grade progression.\nMeningiomas that progress in grade generally have a mutational profile already detectable in the pre-progressed tumour, suggesting an aggressive phenotype . CNA profiling shows frequent alterations in NF2 mutated tumours compared to non NF2 mutated tumours and the pattern of CNAs may be associated with grade progression in a subset of cases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-09T03:22:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006586","title":"Early Colorectal Cancer sequencing study","description":null,"abstract":"we performed whole-exome sequencing (WES) of 106 samples of 37 cases","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006587","title":"Clonal_dynamics_and_mutation_burden_in_male_germline___WGS__CamIVF_","description":"This work aims to study clonal dynamics of pathogenic mutations in male germline. WGS of blood samples provided by IVF clinic patients will be integrated with the sperm samples from a paired study.","abstract":"Little is known about mutagenesis within the hierarchy of spermatogenesis or factors that influence rates of mutation in the testes/sperm. It is likely that mutations in spermatogonia stem cells that confer weaker selective advantage and generate smaller clonal expansions in the testes, become enrich in sperms and transmit to the next generations. However, due to the low sensitivity of standard genomic approaches, subclonal mutations that may only be present in small contiguous areas within testes have been poorly investigated.  Additionally the links of these mutations to male fertility are poorly understood.\n\nThis proposal aims to measure the mutational burden of pathogenic variants in sperm and to identify the processes that underlie their acquisition and their links to fertility.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006588","title":"Clonal_dynamics_and_mutation_burden_in_male_germline___DupSeq__CamIVF_","description":"This work aims to study clonal dynamics of pathogenic mutations in male germline using targeted NanoSeq in sperm samples provided by IVF clinic patients and a custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Little is known about mutagenesis within the hierarchy of spermatogenesis or factors that influence rates of mutation in the testes/sperm. It is likely that mutations in spermatogonia stem cells that confer weaker selective advantage and generate smaller clonal expansions in the testes, become enrich in sperms and transmit to the next generations. However, due to the low sensitivity of standard genomic approaches, subclonal mutations that may only be present in small contiguous areas within testes have been poorly investigated.  Additionally the links of these mutations to male fertility are poorly understood.\n\nThis proposal aims to measure the mutational burden of pathogenic variants in sperm and to identify the processes that underlie their acquisition and their links to fertility.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006589","title":"Clonal_dynamics_and_mutation_burden_in_male_germline___DupSeq__TubulesOxford_","description":"This work aims to study clonal dynamics of pathogenic mutations in male germline using exome NanoSeq of sections of seminiferous tubules from tissue donors. An exome panel will be used to achieve high coverage across coding regions to interrogate known and novel drivers.","abstract":"Little is known about mutagenesis within the hierarchy of spermatogenesis or factors that influence rates of mutation in the testes/sperm. It is likely that mutations in spermatogonia stem cells that confer weaker selective advantage and generate smaller clonal expansions in the testes, become enrich in sperms and transmit to the next generations. However, due to the low sensitivity of standard genomic approaches, subclonal mutations that may only be present in small contiguous areas within testes have been poorly investigated.\n\nThis proposal aims to investigate the mutational landscape in seminiferous tubules.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006590","title":"Breast_Quadrants","description":"This study aims to define the molecular features of normal breast tissues in individuals with evidence of BRCA1 promoter methylation.","abstract":"Recent research has identified BRCA1 promoter methylation in cord blood at levels consistent with mosaicism. BRCA1 methylation in blood  is also associated with an elevated risk of high grade serous ovarian cancer and triple negative breast cancer. However, how BRCA1 methylation spatially manifests in breast tissue is unclear. In this study we aim to establish whether this marker is detectable in normal and cancerous breast tissues and if it is, what spatial patterns it might takes. This will be achieved using a cohort of breast tissue samples from individuals with breast cancer. Samples of normal tissue were obtained from all four quadrants of the breast. We will ascertain the genomic and epigenetic features of both tumours and microscopic anatomical regions of the normal breast. We will identify mutational signatures that indicate the functional loss of BRCA1 and construct spatial maps of epigenetic and genetic features.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006591","title":"Real-time analysis of the cancer genome and fragmentome from plasma and urine short and long cell-free DNA using Nanopore sequencing","description":"Cell-free DNA (cfDNA) can be isolated from blood and/or urine of cancer patients and analyzed with sequencing. Unfortunately, most conventional short-read sequencing methods are technically challenging, labor intensive and time consuming, requiring several days but more typically weeks to obtain interpretable data which are limited by a bias for short cfDNA fragments.\nHere, we demonstrate that with Oxford Nanopore Technologies sequencing  we can achieve economical and ultra-fast delivery of clinical data from liquid biopsies.  \nOur ‘ITSFASTR’ approach is able to deliver copy number aberrations, and cfDNA fragmentation profiles in less than 24 hours from sample collection. The tumor-derived cfDNA fraction calculated from lung cancer patient plasma and urine from bladder cancer patients was highly correlated (R=0.98) to the tumor fraction calculated from conventional short-read sequencing of the same samples. cfDNA size profile and fragmentation patterns in plasma and urine exhibited the typical cfDNA features yet with a significantly higher proportion of informative fragments that exceed 300bp, exhibiting similar tumor fraction than shorter size fragments. Notably, comprehensive fragment-end composition and nucleosome profiling near transcription start sites can be determined from the same data. \nWe propose that ITSFASTR is the first point-of-care solution for obtaining genomic and fragmentomic results from liquid biopsies.","abstract":"Cell-free DNA (cfDNA) can be isolated from blood and/or urine of cancer patients and analyzed with sequencing. Unfortunately, most conventional short-read sequencing methods are technically challenging, labor intensive and time consuming, requiring several days but more typically weeks to obtain interpretable data which are limited by a bias for short cfDNA fragments.\nHere, we demonstrate that with Oxford Nanopore Technologies sequencing  we can achieve economical and ultra-fast delivery of clinical data from liquid biopsies.  \nOur ‘ITSFASTR’ approach is able to deliver copy number aberrations, and cfDNA fragmentation profiles in less than 24 hours from sample collection. The tumor-derived cfDNA fraction calculated from lung cancer patient plasma and urine from bladder cancer patients was highly correlated (R=0.98) to the tumor fraction calculated from conventional short-read sequencing of the same samples. cfDNA size profile and fragmentation patterns in plasma and urine exhibited the typical cfDNA features yet with a significantly higher proportion of informative fragments that exceed 300bp, exhibiting similar tumor fraction than shorter size fragments. Notably, comprehensive fragment-end composition and nucleosome profiling near transcription start sites can be determined from the same data. \nWe propose that ITSFASTR is the first point-of-care solution for obtaining genomic and fragmentomic results from liquid biopsies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-09T15:19:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006592","title":"Whole_exome_sequencing_human_oesophagus","description":"As a control for our CRISPR studies we wish to undertake a whole exome screen of normal oesophagus to look for potential new drivers of clonal expansion.","abstract":"As a control for our CRISPR studies we wish to undertake a whole exome screen of normal oesophagus to look for potential new drivers of clonal expansion.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006593","title":"Whole-Transcriptomic Profiling of Sorted Human Renal Cell Carcinoma Immune Populations","description":"It is poorly understood how the tumor immune micro-environment influences disease progression in renal cell carcinoma (RCC). Here we performed whole-transcriptomic profiling of immune cell populations which were derived from RCC patients representing distinct flow-sorted immune lineages.","abstract":"It is poorly understood how the tumor immune micro-environment influences disease progression in renal cell carcinoma (RCC). Here we performed whole-transcriptomic profiling of immune cell populations which were derived from RCC patients representing distinct flow-sorted immune lineages.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-09T16:02:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006594","title":"RNA sequencing of AD, MCI and control ONS cells","description":null,"abstract":"We  have generated human olfactory neurosphere-derived (ONS) cells from individuals with AD or mild cognitive impairment (MCI), and their cognitively healthy controls, and performed global RNA sequencing to determine gene expression changes in ONS cells.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-12T11:21:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006595","title":"High-throughput telomere length measurement at nucleotide resolution using the PacBio high fidelity sequencing platform, P49-P104 and run1 replicates","description":"Telomeres are specialized nucleoprotein structures at the ends of linear chromosomes that are essential for the stability as well as the complete replication of the human genome. The progressive shortening of steady-state telomere length in normal human somatic cells is a promising biomarker for age-associated diseases. However, there remain substantial challenges in quantifying telomere length in clinics and research laboratories due to the lack of accurate and high-throughput telomere length measurement method. Here, we describe a novel workflow to capture and analyze telomeres accurately at the single-nucleotide resolution. By using newly designed telobaits that are complementary to the single-stranded G-rich 3’ telomeric overhangs, we can specifically and efficiently capture full-length telomeres and subject them to single-molecule real-time (SMRT) sequencing. We show that the telomere length can be measured at nucleotide resolution using the PacBio high fidelity (HiFi) sequencing platform, which provides the necessary accuracy and throughput to uncover the steady-state telomere length distribution in human culture cell lines as well as clinical patient samples. This new method is a valuable tool not only in population-wide epidemiology studies but also for the longitudinal assessment of telomere attrition in individuals. Our results also reveal the extreme heterogeneity of telomeric variant sequences (TVSs) that is dispersed throughout the telomere repeat region. Importantly, the unique distribution pattern and sequence of TVSs in individuals may be used as a fingerprint for sample identification. In addition, the presence of TVSs disrupts the continuity of the canonical (5’-TTAGGG-3’)n telomere repeats, which could affect the binding of shelterin complexes at the chromosomal ends. Therefore, TVSs may act as a form of genetic polymorphisms that impairs telomere protection. Together with the absolute telomere length in each individual, TVSs may have profound implications in human aging and diseases.","abstract":"Telomeres are specialized nucleoprotein structures at the ends of linear chromosomes that are essential for the stability as well as the complete replication of the human genome. The progressive shortening of steady-state telomere length in normal human somatic cells is a promising biomarker for age-associated diseases. However, there remain substantial challenges in quantifying telomere length in clinics and research laboratories due to the lack of accurate and high-throughput telomere length measurement method. Here, we describe a novel workflow to capture and analyze telomeres accurately at the single-nucleotide resolution. By using newly designed telobaits that are complementary to the single-stranded G-rich 3’ telomeric overhangs, we can specifically and efficiently capture full-length telomeres and subject them to single-molecule real-time (SMRT) sequencing. We show that the telomere length can be measured at nucleotide resolution using the PacBio high fidelity (HiFi) sequencing platform, which provides the necessary accuracy and throughput to uncover the steady-state telomere length distribution in human culture cell lines as well as clinical patient samples. This new method is a valuable tool not only in population-wide epidemiology studies but also for the longitudinal assessment of telomere attrition in individuals. Our results also reveal the extreme heterogeneity of telomeric variant sequences (TVSs) that is dispersed throughout the telomere repeat region. Importantly, the unique distribution pattern and sequence of TVSs in individuals may be used as a fingerprint for sample identification. In addition, the presence of TVSs disrupts the continuity of the canonical (5’-TTAGGG-3’)n telomere repeats, which could affect the binding of shelterin complexes at the chromosomal ends. Therefore, TVSs may act as a form of genetic polymorphisms that impairs telomere protection. Together with the absolute telomere length in each individual, TVSs may have profound implications in human aging and diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-12T17:13:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006596","title":"Transcriptomic profiles of chronic lymphocytic leukemia before and after frontline therapy: 5-year results from the randomized CLL14 study","description":"CLL14 (NCT02242942) is a multinational, open-label Phase III study designed to compare venetoclax-obinutuzumab (Ven-Obi) versus chlorambucil-obinutuzumab (Clb-Obi) in previously untreated patients with CLL and co-existing conditions. Between Aug 7, 2015, and Aug 4, 2016, 432 patients were enrolled and randomly assigned to receive either venetoclax plus obinutuzumab (Ven-Obi, n=216) or chlorambucil plus obinutuzumab (Clb-Obi, n=216). In both study arms, patients received fixed-duration treatment of overall 12 cycles, each cycle 28 days long, and entered subsequent post-treatment surveillance. Peripheral blood samples were collected before the start of therapy, as well as every 3-6 months during and after therapy, including at the time of disease progression. The primary endpoint of the study was progression-free survival, secondary endpoints included overall response rate, minimal residual disease response, and overall survival. The primary read-out was conducted after a median follow-up of 28.1 months, when the primary endpoint was met with 30 primary end-point events (disease progression or death) in the Ven-Obi arm and 77 in the Clb-Obi arm (hazard ratio, 0.35; 95% confidence interval [CI], 0.23 to 0.53;P&lt;0.001). Follow-up is ongoing until 9 years after the last patient enrollment. In an exploratory analysis, bulk RNAseq was conducted with CD19-enriched blood from patients before start of therapy (418 patients) and at first relapse (44 patients).","abstract":"CLL14 (NCT02242942) is a multinational, open-label Phase III study designed to compare venetoclax-obinutuzumab (Ven-Obi) versus chlorambucil-obinutuzumab (Clb-Obi) in previously untreated patients with CLL and co-existing conditions. Between Aug 7, 2015, and Aug 4, 2016, 432 patients were enrolled and randomly assigned to receive either venetoclax plus obinutuzumab (Ven-Obi, n=216) or chlorambucil plus obinutuzumab (Clb-Obi, n=216). In both study arms, patients received fixed-duration treatment of overall 12 cycles, each cycle 28 days long, and entered subsequent post-treatment surveillance. Peripheral blood samples were collected before the start of therapy, as well as every 3-6 months during and after therapy, including at the time of disease progression. The primary endpoint of the study was progression-free survival, secondary endpoints included overall response rate, minimal residual disease response, and overall survival. The primary read-out was conducted after a median follow-up of 28.1 months, when the primary endpoint was met with 30 primary end-point events (disease progression or death) in the Ven-Obi arm and 77 in the Clb-Obi arm (hazard ratio, 0.35; 95% confidence interval [CI], 0.23 to 0.53;P&lt;0.001). Follow-up is ongoing until 9 years after the last patient enrollment. In an exploratory analysis, bulk RNAseq was conducted with CD19-enriched blood from patients before start of therapy (418 patients) and at first relapse (44 patients).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-13T19:18:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006597","title":"Defective homologous recombination in HCC","description":null,"abstract":"Backgrounds and Aims: We performed an in-depth examination of pathogenic germline (PGVs) and somatic variants in DNA damage response (DDR) genes in hepatocellular carcinoma (HCC) to explore their clinical and genomic impacts. \nApproach and Results: We used a merged whole exome or RNA sequencing dataset derived from in-house (n=230) and TCGA (n=362) databases of multiethnic HCC samples. We also evaluated synthetic lethal approaches targeting mutations in homologous recombination (HR) genes using HCC cells selected from five public-access genomic databases of human cancer cell lines. A total of 110 PGVs in DDR pathways in 96 patients were selected. Of the PGV carriers, 44 were HR-altered and found to be independently associated with poorer disease-free survival after HCC resection. The most frequently altered HR gene in both germline and somatic tissues was POLQ, and this variant was detected in 22.7% (10/44) and 23.8% (5/21) of all the corresponding carriers, respectively. PGVs in HR were significantly associated with upregulation of proliferation and replication-related genes, and familial risk of HCC. Samples harboring PGVs in HR with loss-of-heterozygosity were most strongly correlated with the genomic footprints of deficient HR, such as mutation burden and denovoSig2 (analogous to COSMIC 3), and poor outcome. Pharmacologic experiments with HCC cells defective in BRCA2 or POLQ suggested that tumors with this phenotype are synthetic lethal with poly(ADP-ribose) polymerase inhibitors.\nConclusions: Our findings suggest that germline HR defects in HCC tend to confer a poor prognosis and result in distinctive genomic scarring. Tests of the clinical benefits of HR-directed treatments in the affected patients are needed.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006598","title":"Treatment-mediated selection of lethal prostate cancer clones defined by copy number architectures","description":"Despite initial responses to hormone treatment, metastatic prostate cancer invariably evolves to a lethal state. To characterize the intra-patient relationships of metastases that evade treatment, we performed genome- wide copy number profiling and bespoke approaches targeting the androgen receptor (AR) on 142 metastatic regions from 10 organs harvested post-mortem from nine men who died from prostate cancer. We identified diverse and patient-unique alterations clustering around the AR in metastases from every patient with evidence of independent acquisition of related genomic changes within an individual and, in some patients, the co-existence of AR-neutral clones. Using the genomic boundaries of pan-autosome copy number change, we confirmed a common clone of origin across metastases and diagnostic biopsies; and identified in individual patients, clusters of metastases occupied by dominant clones with diverged autosomal copy number alterations. Autosome-defined clusters were characterized by cluster-specific AR gene architectures that in two index cases were topologically more congruent than by chance (p-values 0.03, 3.07x10-8). Integration with anatomical site suggested patterns of spread and points of genomic divergence. Copy number boundaries identified treatment-selected clones with putatively distinct lethal trajectories.","abstract":"Despite initial responses to hormone treatment, metastatic prostate cancer invariably evolves to a lethal state. To characterize the intra-patient relationships of metastases that evade treatment, we performed genome- wide copy number profiling and bespoke approaches targeting the androgen receptor (AR) on 142 metastatic regions from 10 organs harvested post-mortem from nine men who died from prostate cancer. We identified diverse and patient-unique alterations clustering around the AR in metastases from every patient with evidence of independent acquisition of related genomic changes within an individual and, in some patients, the co-existence of AR-neutral clones. Using the genomic boundaries of pan-autosome copy number change, we confirmed a common clone of origin across metastases and diagnostic biopsies; and identified in individual patients, clusters of metastases occupied by dominant clones with diverged autosomal copy number alterations. Autosome-defined clusters were characterized by cluster-specific AR gene architectures that in two index cases were topologically more congruent than by chance (p-values 0.03, 3.07x10-8). Integration with anatomical site suggested patterns of spread and points of genomic divergence. Copy number boundaries identified treatment-selected clones with putatively distinct lethal trajectories.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-14T12:48:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006599","title":"Defective homologous recombination in HCC","description":"Backgrounds and Aims: We performed an in-depth examination of pathogenic germline (PGVs) and somatic variants in DNA damage response (DDR) genes in hepatocellular carcinoma (HCC) to explore their clinical and genomic impacts. \n\nApproach and Results: We used a merged whole exome or RNA sequencing dataset derived from in-house (n=230) and TCGA (n=362) databases of multiethnic HCC samples.","abstract":"Backgrounds and Aims: We performed an in-depth examination of pathogenic germline (PGVs) and somatic variants in DNA damage response (DDR) genes in hepatocellular carcinoma (HCC) to explore their clinical and genomic impacts. \n\nApproach and Results: We used a merged whole exome or RNA sequencing dataset derived from in-house (n=230) and TCGA (n=362) databases of multiethnic HCC samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-14T13:23:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006600","title":"Genomic landscape of DS-ALL","description":null,"abstract":"We analyzed the genomic landscape of 295 samples of acute lymphoblastic leukemia in children with Down syndrome. By integrating paired leukemia-germline whole genome sequencing (n=244) and whole transcriptome sequencing (n=249), we classified DS-ALL into 16 subtypes, each characterized with unique genomic alterations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-14T20:25:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006601","title":"Cetuximab treatment of metastasis-derived organoids (LMO)","description":null,"abstract":"Dataset of organoids both treated with the targeted drug Cetuximab and placebo","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-15T10:11:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006602","title":"HLF COPD Transcriptomics","description":"We generated transcriptomes of primary human lung fibroblasts (HLFs) isolated from distal parenchyma of ex-smoker controls and COPD patients, with both mild and severe disease. RNA sequencing analysis demonstrated dysregulation of genes involved in proliferation, DNA repair, and extracellular matrix organization.","abstract":"We generated transcriptomes of primary human lung fibroblasts (HLFs) isolated from distal parenchyma of ex-smoker controls and COPD patients, with both mild and severe disease. RNA sequencing analysis demonstrated dysregulation of genes involved in proliferation, DNA repair, and extracellular matrix organization.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-15T13:00:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006603","title":"HLF COPD DNA Methylomics","description":null,"abstract":"Patients with chronic obstructive pulmonary disease (COPD) are still waiting for curative treatments. Considering the environmental cause of COPD (e.g., cigarette smoke) and disease phenotypes, including stem-cell senescence and impaired differentiation, we hypothesized that COPD will be associated with altered epigenetic signaling in lung cells. We generated genome-wide DNA methylation maps at single CpG resolution of primary human lung fibroblasts (HLFs) isolated from distal parenchyma of ex-smoker controls and COPD patients, with both mild and severe disease. The epigenetic landscape is markedly changed in lung fibroblasts across COPD stages, with DNA methylation changes occurring predominantly in regulatory regions, including promoters and enhancers.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-15T13:00:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006604","title":"Hi-C analysis of metastatic prostate tumors","description":"DNA strands have a complex and highly structured three-dimensional shape within the nucleus that has profound but poorly characterized impacts on transcriptional activity. Herein, we performed the first integrated deep Hi-C sequencing on 80 metastatic castration-resistant prostate cancer biopsy samples from the West Coast Dream Team consortium.","abstract":"DNA strands have a complex and highly structured three-dimensional shape within the nucleus that has profound but poorly characterized impacts on transcriptional activity. Herein, we performed the first integrated deep Hi-C sequencing on 80 metastatic castration-resistant prostate cancer biopsy samples from the West Coast Dream Team consortium.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-15T13:21:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006605","title":"DNA and RNA sequencing data from Ovarian Carcinosarcoma patients from the Glasgow Cohort.","description":"In this study, we analysed DNA and RNA sequencing data from Ovarian Carcinosarcoma patients, from isolated carcinoma and sarcoma components and investigated DNA variants as well as gene expression. Genomic analyses from this data and further investigation from preclinical models of ovarian carcinosarcoma support the conversion theory for disease development and indicate that microtubule inhibitors could be used to suppress EMT and stimulate anti-tumour immunity.","abstract":"In this study, we analysed DNA and RNA sequencing data from Ovarian Carcinosarcoma patients, from isolated carcinoma and sarcoma components and investigated DNA variants as well as gene expression. Genomic analyses from this data and further investigation from preclinical models of ovarian carcinosarcoma support the conversion theory for disease development and indicate that microtubule inhibitors could be used to suppress EMT and stimulate anti-tumour immunity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-15T15:27:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006606","title":"Molecular_QTLs_of_Human_umbilical_vein_endothelial_cells__HUVECs__","description":"We aim to characterise the range of phenotypic variation in gene expression, epigenetic regulation and intermediate functional phenotypes and its underlying genetic determinants in primary Human umbilical vein endothelial cells (HUVECs) samples We will measure gene expression by RNA sequencing (RNA-seq), genome functionality by ATAC-sequencing (ATAC-seq, to determine which regions are in an open chromatin state) and by determining H3 lysine 27acetylation (H3K27ac), a marker of active transcriptional enhancers, localisation genome wide by chromatin immunoprecipitation coupled with sequencing (ChIP-seq).","abstract":"We aim to characterise the range of phenotypic variation in gene expression, epigenetic regulation and intermediate functional phenotypes and its underlying genetic determinants in primary Human umbilical vein endothelial cells (HUVECs) samples We will measure gene expression by RNA sequencing (RNA-seq), genome functionality by ATAC-sequencing (ATAC-seq, to determine which regions are in an open chromatin state) and by determining H3 lysine 27acetylation (H3K27ac), a marker of active transcriptional enhancers, localisation genome wide by chromatin immunoprecipitation coupled with sequencing (ChIP-seq).","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-16T09:27:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006607","title":"Targeted_NanoSeq__Oesophagus_","description":"Targeted NanoSeq in oesophagus samples from a number of donors, including donors with and without malignancy. Samples may contain pre-malignant histology A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across a large number of oesophagus specimens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006608","title":"Targeted_NanoSeq__Skin_","description":"argeted NanoSeq in skin samples from a number of donors, including donors with and without malignancy. Samples may contain pre-malignant histology A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across a large number of skin specimens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006609","title":"Long-read sequencing for cell-free DNA analysis (human pacbio)","description":"8 pregnant women at the 3rd trimesters, 4 hepatitis B carriers, and 4 patients  with hepatocellular carcinoma","abstract":"8 pregnant women at the 3rd trimesters, 4 hepatitis B carriers, and 4 patients  with hepatocellular carcinoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-19T09:47:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006610","title":"The clinical utility of genomics in childhood cancer extends beyond targetable mutations - WGS data","description":"We deeply sequenced 864 cancer-associated genes and the complete genomes and transcriptomes for 300 pediatric and adolescent/young adult (AYA) patients with poor prognosis or rare tumors. Using integrative somatic-germline analyses, we assessed the clinical utility of cancer genomics in this population. Clinically actionable variants were identified in 56% of patients.  Improved diagnostic accuracy led to modified management in a subset. Therapeutically targetable variants, found in 54% of patients, were of unanticipated timing and type, with over 20% of these derived from the germline. Enrichment in corroborating mutational signature 3 (‘BRCAness’) in patients with germline homologous recombination defects suggests they are drivers of pediatric cancers and potential targets for PARP inhibition. Comprehensive somatic-germline cancer genomic profiling is useful at multiple points in the care trajectory for pediatric/AYA patients, supporting its integration into early clinical management. Re-biopsy at the time of relapse should be considered, and specific attention to mutational burden is indicated. Defective DNA repair genes in the germline may represent important targetable drivers.","abstract":"We deeply sequenced 864 cancer-associated genes and the complete genomes and transcriptomes for 300 pediatric and adolescent/young adult (AYA) patients with poor prognosis or rare tumors. Using integrative somatic-germline analyses, we assessed the clinical utility of cancer genomics in this population. Clinically actionable variants were identified in 56% of patients.  Improved diagnostic accuracy led to modified management in a subset. Therapeutically targetable variants, found in 54% of patients, were of unanticipated timing and type, with over 20% of these derived from the germline. Enrichment in corroborating mutational signature 3 (‘BRCAness’) in patients with germline homologous recombination defects suggests they are drivers of pediatric cancers and potential targets for PARP inhibition. Comprehensive somatic-germline cancer genomic profiling is useful at multiple points in the care trajectory for pediatric/AYA patients, supporting its integration into early clinical management. Re-biopsy at the time of relapse should be considered, and specific attention to mutational burden is indicated. Defective DNA repair genes in the germline may represent important targetable drivers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-19T15:19:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006611","title":"Multiomic profiling of in vitro differentiated human T-cell subsets derived from CD34+ umbilical cord blood","description":null,"abstract":"To characterize the molecular changes that accompany human T-cell differentiation, we generated RNA-seq, ChIP-seq and whole genome bisulfite sequencing data from T-cell subsets derived in vitro from human CD34+ umbilical cord blood.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006612","title":"Hi-C analysis of metastatic prostate tumors - Part 2","description":"DNA strands have a complex and highly structured three-dimensional shape within the nucleus that has profound but poorly characterized impacts on transcriptional activity. Herein, we performed the first integrated deep Hi-C sequencing on 80 metastatic castration-resistant prostate cancer biopsy samples from the West Coast Dream Team consortium.","abstract":"DNA strands have a complex and highly structured three-dimensional shape within the nucleus that has profound but poorly characterized impacts on transcriptional activity. Herein, we performed the first integrated deep Hi-C sequencing on 80 metastatic castration-resistant prostate cancer biopsy samples from the West Coast Dream Team consortium.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-19T23:00:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006613","title":"Tumorigenic role of Musashi-2 in aggressive mantle cell lymphoma","description":"SOX11 is overexpressed in the highly aggressive conventional mantle cell lymphoma (MCL) but rarely in the indolent non-nodal MCL subtype. We performed RNA-seq of SOX11+ and SOX11- MCLs to search for SOX11-regulated genes that contributed to MCL clinical evolution, identifying Musashi-2 (MSI2) stem cell-related gene. By performing RNA-seq upon MSI2 knockdown or inhibition in MCL, we identified MSI2 as a potential target to inhibit drug resistance in aggressive MCLs.","abstract":"SOX11 is overexpressed in the highly aggressive conventional mantle cell lymphoma (MCL) but rarely in the indolent non-nodal MCL subtype. We performed RNA-seq of SOX11+ and SOX11- MCLs to search for SOX11-regulated genes that contributed to MCL clinical evolution, identifying Musashi-2 (MSI2) stem cell-related gene. By performing RNA-seq upon MSI2 knockdown or inhibition in MCL, we identified MSI2 as a potential target to inhibit drug resistance in aggressive MCLs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-20T10:10:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006614","title":"Adaptive single-KIR+NKG2C+ NK cells expanded from superdonors show potent missing-self reactivity and efficiently control HLA-mismatched acute myeloid leukemia","description":null,"abstract":"Describe a novel GMP-compliant protocol to expand clinically relevant numbers of adaptive NK cells from third-party ‘superdonors’. These NK cells provide strong reactivity in a mouse model of AML as well as against primary AML blasts ex vivo. How this study might affect research, practice or policy:  These pre-clinical data demonstrate the feasibility of an NK cell-based cell therapy with a non-engineered and yet highly specific NK cell population, representing the first route to clinical testing of missing-self recognition.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-03-12T10:03:41.91476+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006615","title":"Mosaic_CRISPR_Drug_Combinations___Dual_Guide","description":"The study aims to perform genome-wide loss-of-function CRISPR-Cas9 screens across genetically annotated human cancer cell lines to identify target combinations. \nAll sequencing is performed on PCR products from the amplification of gRNA segments introduced into the lines.","abstract":"The goal of this project is to identify potential novel drug target combinations for use in cancer biology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006616","title":"The_Little_Princess_Knowledge_Bank_WES","description":"We propose to build a genetic knowledge bank of Wilms tumour that integrates clinical outcome\ndata with a genetic, epigenetic, and transcriptomic survey of 1,000 Wilms tumours","abstract":"The purpose of the knowledge bank is to serve as a community resource and to address the following specific\nquestions about Wilms tumour:\n(1) Do genetic, epigenetic, or transcriptional features predict outcome and thus lend themselves to\ntreatment stratification?\n(2) What are the genetic drivers of Wilms tumour, considering the entire histological spectrum of\nWilms tumour including the most common subtypes classified as intermediate risk?","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006617","title":"microRNA and isomiR profiling of Stage 1 epithelial ovarian carcinoma","description":null,"abstract":"Stage 1 epithelial ovarian cancer (EOC) has generally a favorable prognosis, but a significant percentage (30%) of patients relapse after treatment and die. The currently available markers are neither sensitive nor specific enough to predict the risk of relapse, thus low risk and high risk patients are treated in the same manner. \nThis study is a characterization  of microRNA and microRNA isoforms (isomiR) in a cohort of Stage 1 epithelial ovarian cancer samples collected from two independent tissue collections, as part of an effort to find new biomarkers with diagnostic and prognostic value.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-21T13:29:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006618","title":"Nasal brushes part 1","description":null,"abstract":"Nasal Brushes scRNA-seq healthy and asthma pt 1","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006619","title":"HG_G3424_Cherrypicking_of_IBD_Samples","description":"The overall objective is to test the hypothesis that clonal haematopoiesis (CH) is associated with immune-mediated inflammatory disease","abstract":"The overall objective is to test the hypothesis that clonal haematopoiesis (CH) is associated with immune-mediated inflammatory disease","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006620","title":"Spatial_transcriptomic_profiling_of_NTCU_treated_mice_VISIUM","description":"his study aims to characterize the ability of NTCU mice to serve as a model system for lung cancer development. For this purpose, 10X VISIUM spatial transcriptomics of mouse lungs at different time points after NTCU treatment as well as healthy, age-matched controls will be utilised to profile the phenotypic changes of cellular populations in the lung. We will compare the development through time as well as aim to characterise the abundance of immune cell populations in the mouse lung. Furthermore, we wil levaluate distinct spatial locations of these cellular populations in the lung.","abstract":"his study aims to characterize the ability of NTCU mice to serve as a model system for lung cancer development. For this purpose, 10X VISIUM spatial transcriptomics of mouse lungs at different time points after NTCU treatment as well as healthy, age-matched controls will be utilised to profile the phenotypic changes of cellular populations in the lung. We will compare the development through time as well as aim to characterise the abundance of immune cell populations in the mouse lung. Furthermore, we wil levaluate distinct spatial locations of these cellular populations in the lung.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006621","title":"Genetic characterization patients affected by Cancer of Unknown Primary","description":"The genetic changes sustaining the development of human Cancers of Unknown Primary (CUP) remain elusive. Here we report the genomic profiling of 14 rigorously selected CUP samples. Although no specific recurring mutation in known driver genes was found, a comparison of the mutational landscape of CUPs with that of most other human tumor types revealed a consistent change in diverse genes belonging to the axon guidance KEGG pathway.","abstract":"The genetic changes sustaining the development of human Cancers of Unknown Primary (CUP) remain elusive. Here we report the genomic profiling of 14 rigorously selected CUP samples. Although no specific recurring mutation in known driver genes was found, a comparison of the mutational landscape of CUPs with that of most other human tumor types revealed a consistent change in diverse genes belonging to the axon guidance KEGG pathway.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-22T16:25:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006622","title":"Single_cell_expression_analysis_of_inflammation_and_fibrosis_development_and_progression_in_Crohn_s_Disease","description":"Inflammatory Bowel Disease (IBD) currently affects more than 7 million people worldwide. Crohn’s Disease (CD) is one type of IBD that may cause fibrostenosing lesions in some patients, requiring surgical excision of parts of the bowel, as the fibrotic scar tissue can cause obstruction of the intestinal lumen. The development of more effective treatments is currently limited with the linear disease models which are not able to fully characterize the complex interactions between different cell types, function and states. This project will allow more detailed single-cell expression and molecular characterisation of both the processes of development and progression of inflammation and fibrosis, including why the terminal ileum and ascending colon are particularly susceptible. Current treatment strategies to manage Crohn’s Disease may involve targeting multiple inflammatory pathways simultaneously or sequentially and it will be crucial to understand how this may be influenced by the surrounding cell types and states. The work described here will be a strategic tool to investigate the clinical phenotype and complex biological interactions at the cellular level. The single-cell expression analysis will reveal the cellular types, sub-types and interactions within each sample.","abstract":"Inflammatory Bowel Disease (IBD) currently affects more than 7 million people worldwide. Crohn’s Disease (CD) is one type of IBD that may cause fibrostenosing lesions in some patients, requiring surgical excision of parts of the bowel, as the fibrotic scar tissue can cause obstruction of the intestinal lumen. The development of more effective treatments is currently limited with the linear disease models which are not able to fully characterize the complex interactions between different cell types, function and states. This project will allow more detailed single-cell expression and molecular characterisation of both the processes of development and progression of inflammation and fibrosis, including why the terminal ileum and ascending colon are particularly susceptible. Current treatment strategies to manage Crohn’s Disease may involve targeting multiple inflammatory pathways simultaneously or sequentially and it will be crucial to understand how this may be influenced by the surrounding cell types and states. The work described here will be a strategic tool to investigate the clinical phenotype and complex biological interactions at the cellular level. The single-cell expression analysis will reveal the cellular types, sub-types and interactions within each sample.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006623","title":"INCISE_WES","description":"British Society of Gastroenterology (BSG) guidelines are used to define patients who are eligible for follow-up colonoscopy.  Approximately only 50% of patients who undergo surveillance colonoscopies develop future polyps, which means many patients undergo an unpleasant, invasive procedure, at a considerable cost to the NHS and with little patient benefit.   Therefore, there is a need to improve the risk stratification tool for bowl cancer surveillance program. INCISE aims to create a new risk stratification tool to improve the BSG risk score by combining clinical data with immunohistochemistry, digital pathology, transcriptomics and genomics.","abstract":"British Society of Gastroenterology (BSG) guidelines are used to define patients who are eligible for follow-up colonoscopy.  Approximately only 50% of patients who undergo surveillance colonoscopies develop future polyps, which means many patients undergo an unpleasant, invasive procedure, at a considerable cost to the NHS and with little patient benefit.   Therefore, there is a need to improve the risk stratification tool for bowl cancer surveillance program. INCISE aims to create a new risk stratification tool to improve the BSG risk score by combining clinical data with immunohistochemistry, digital pathology, transcriptomics and genomics.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006624","title":"TransSCOT_WES","description":"TransSCOT is the translational arm of the SCOT trial, where samples of paraffin embedded tumour tissue (obtained at surgical resection of SCOT patient’s primary tumour prior to entry into the trial) and blood samples (serum sample and EDTA sample) were collected as part of a sub-study research initiative.  The SCOT trial (ISRCTN59757862) was an “international, randomised, phase 3, non-inferiority trial” involving adult patients with high-risk stage II or stage III colorectal cancer. Patients received either 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy, consisting of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin).  The study found that 3 months of oxaliplatin-containing adjuvant chemotherapy was, as anticipated, non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer.  In addition this treatment regime was found to be associated with less toxicity and better quality of life.  We would like to identify molecular and histological features of CRCs thereby obtaining clues about the underlying mechanisms of increased cancer risk.  We will use these for analysis with other clinicopathological variables, and its association with clinical outcome both by univariable and multivariable Cox proportional hazards regression analysis.","abstract":"TransSCOT is the translational arm of the SCOT trial, where samples of paraffin embedded tumour tissue (obtained at surgical resection of SCOT patient’s primary tumour prior to entry into the trial) and blood samples (serum sample and EDTA sample) were collected as part of a sub-study research initiative.  The SCOT trial (ISRCTN59757862) was an “international, randomised, phase 3, non-inferiority trial” involving adult patients with high-risk stage II or stage III colorectal cancer. Patients received either 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy, consisting of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin).  The study found that 3 months of oxaliplatin-containing adjuvant chemotherapy was, as anticipated, non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer.  In addition this treatment regime was found to be associated with less toxicity and better quality of life.  We would like to identify molecular and histological features of CRCs thereby obtaining clues about the underlying mechanisms of increased cancer risk.  We will use these for analysis with other clinicopathological variables, and its association with clinical outcome both by univariable and multivariable Cox proportional hazards regression analysis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006625","title":"Targeted_NanoSeq__Endometrium_","description":"Targeted NanoSeq on normal endometrial samples from a number of donors. Samples may contain pre-malignant histology A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape in the normal endometrium","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006626","title":"Targeted_NanoSeq__FallopianTube_","description":"Targeted NanoSeq on normal fallopian tube samples from a number of donors. Samples may contain pre-malignant histology A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape in normal fallopian tubes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006627","title":"DERMATLAS__Pilar_cyst_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are pilar cysts.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are pilar cysts.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006628","title":"IBD_RESPONSE","description":"IBD is a severely debilitating disease that affects around 1 in 200 people in the UK. The two common forms of IBD, ulcerative colitis (UC) and Crohn’s disease (CD), are characterised by chronic relapsing inflammation of the gastrointestinal tract. Current therapies are expensive, have major side-effects, and are ineffective in many patients. For example, 40% of patients do not respond to anti-TNFa therapy (“primary non-response”) and of the 60% that respond, 40% lose response (secondary loss of response), which is primarily thought to be due to development of anti-drug antibodies (ADAs). Up to 50% of CD patients and 15% of UC patients will ultimately require life-changing surgery for medically refractory disease. There is thus a clear need for more effective therapies and biomarkers that are predictive of disease progression and therapeutic response. Unfortunately, the biological basis of IBD and therapy response are incompletely understood. It is believed that patient outcomes are the result of interactions between genotype, the gut microbiome and the environment (e.g. smoking, diet, pathogens), all of which influence human cellular phenotypes.  Data from the study will answer the following questions: 1. What are the genes, cell-types and pathways that mediate risk of IBD? 2. What are the genes, cell-types and pathways that mediate disease progression and treatment response in IBD? 3. To what extent do single-cell transcriptomes in relevant cells predict disease course and treatment response? 4. What is the causal relationship between the gut microbiome, intestinal gene expression, TCR/BCR variation and IBD progression and drug response.","abstract":"Single cell sequencing of blood and gut biopsies ascertained from IBD patients before and after administration of first biologic therapy (mainly anti-TNFs).\nIBD is a severely debilitating disease that affects around 1 in 200 people in the UK. The two common forms of IBD, ulcerative colitis (UC) and Crohn’s disease (CD), are characterised by chronic relapsing inflammation of the gastrointestinal tract. Current therapies are expensive, have major side-effects, and are ineffective in many patients. For example, 40% of patients do not respond to anti-TNFa therapy (“primary non-response”) and of the 60% that respond, 40% lose response (secondary loss of response), which is primarily thought to be due to development of anti-drug antibodies (ADAs). Up to 50% of CD patients and 15% of UC patients will ultimately require life-changing surgery for medically refractory disease. There is thus a clear need for more effective therapies and biomarkers that are predictive of disease progression and therapeutic response. Unfortunately, the biological basis of IBD and therapy response are incompletely understood. It is thought that patient outcomes are the result of interactions between genotype, the gut microbiome and the environment (e.g. smoking, diet, pathogens), all of which influence host cell phenotypes. The longitudinal IBD-Response study has been funded by the MRC to assess these interactions, and their effect on patient outcomes, in a cohort of 1325 IBD patients recruited from up to 40 hospitals across the UK who are about to start their first biological therapy (mostly anti-TNFs). \nHere, we will generate 10X 3’ scRNA-seq data on blood samples ascertained from 1325 IBD-Response participants at week zero (prior to drug administration) and week 14 (after treatment). Sequencing of 2000-3000 cells per donor will be performed on an Illumina Novaseq, with 30-50,000 reads/cell.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006629","title":"Long-read sequencing of diagnosis and post-therapy medulloblastoma reveals complex rearrangement patterns and epigenetic signatures (Hipo_021)","description":"Cancer genomes harbor a broad spectrum of structural variants (SV) driving tumorigenesis, a relevant subset of which escape discovery using short-read sequencing. We employed Oxford Nanopore Technologies (ONT) long-read sequencing in a paired diagnostic and post- therapy medulloblastoma  to unravel the haplotype-resolved somatic genetic and epigenetic landscape. We assemble complex rearrangements and such associated with telomeric sequences, including a 1.55 Megabasepair chromothripsis event. We uncover a complex SV pattern termed ‘templated insertion thread’ (TI thread), characterized by short (mostly &lt;1kb) insertions showing prevalent self-concatenation into highly amplified structures of up to 50kbp in size. TI threads occur in 3% of cancers, with a prevalence ranging to 74% in liposarcoma, and frequent colocalization with chromothripsis. We also perform long-read based methylome profiling and discover allele-specific methylation (ASM) effects, complex rearrangements exhibiting differential methylation, and differential promoter methylation in cancer-driver genes. Our study shows the advantage of long-read sequencing in the discovery and characterization of complex somatic rearrangements.","abstract":"Cancer genomes harbor a broad spectrum of structural variants (SV) driving tumorigenesis, a relevant subset of which escape discovery using short-read sequencing. We employed Oxford Nanopore Technologies (ONT) long-read sequencing in a paired diagnostic and post- therapy medulloblastoma  to unravel the haplotype-resolved somatic genetic and epigenetic landscape. We assemble complex rearrangements and such associated with telomeric sequences, including a 1.55 Megabasepair chromothripsis event. We uncover a complex SV pattern termed ‘templated insertion thread’ (TI thread), characterized by short (mostly &lt;1kb) insertions showing prevalent self-concatenation into highly amplified structures of up to 50kbp in size. TI threads occur in 3% of cancers, with a prevalence ranging to 74% in liposarcoma, and frequent colocalization with chromothripsis. We also perform long-read based methylome profiling and discover allele-specific methylation (ASM) effects, complex rearrangements exhibiting differential methylation, and differential promoter methylation in cancer-driver genes. Our study shows the advantage of long-read sequencing in the discovery and characterization of complex somatic rearrangements.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-23T10:27:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006630","title":"Test Study for EGA using data from 1000 Genomes Project - Really small CRAM, BAM and VCF files used for testing","description":"This is a test study for EGA using data from 1000 Genomes Project - Phase 3, specifically created to add more diversity to the existing dataset EGAD00001003338. This Test Study should NOT be confused with the real study of 1000 Genomes Project - Phase 3. Specifically, this study encompasses 2 CRAM, BAM and VCF files, each not bigger than 200Kb, used for testing downloads and monitoring services, and their respective indexes: crai for crams, bai for bams, and tbi and csi for vcfs.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006631","title":"The Genetic Landscape of Ocular Adnexa MALT Lymphoma Reveals Frequent Aberrations in NFAT and MEF2B Signaling Pathways","description":"A comprehensive constellation of somatic non-silent mutations and copy number (CN) variations in ocular adnexa marginal zone lymphoma (OAMZL) is unknown. By utilizing whole-exome sequencing in 69 tumors we define the genetic landscape of OAMZL. Mutations and CN changes in CABIN1 (30%), RHOA (26%), TBL1XR1 (22%), and CREBBP (17%) and inactivation of TNFAIP3 (26%) were among the most common aberrations. Candidate cancer driver genes cluster in the B-cell receptor (BCR), NFkB, NOTCH and NFAT signaling pathways. One of the most commonly altered genes is CABIN1, a calcineurin inhibitor acting as a negative regulator of the NFAT and MEF2B transcriptional activity. CABIN1 deletions enhance BCR-stimulated NFAT and MEF2B transcriptional activity, while CABIN1 mutations enhance only MEF2B transcriptional activity by impairing binding of mSin3a to CABIN1. Our data provide an unbiased identification of genetically altered genes that may play a role in the molecular pathogenesis of OAMZL and serve as therapeutic targets.","abstract":"A comprehensive constellation of somatic non-silent mutations and copy number (CN) variations in ocular adnexa marginal zone lymphoma (OAMZL) is unknown. By utilizing whole-exome sequencing in 69 tumors we define the genetic landscape of OAMZL. Mutations and CN changes in CABIN1 (30%), RHOA (26%), TBL1XR1 (22%), and CREBBP (17%) and inactivation of TNFAIP3 (26%) were among the most common aberrations. Candidate cancer driver genes cluster in the B-cell receptor (BCR), NFkB, NOTCH and NFAT signaling pathways. One of the most commonly altered genes is CABIN1, a calcineurin inhibitor acting as a negative regulator of the NFAT and MEF2B transcriptional activity. CABIN1 deletions enhance BCR-stimulated NFAT and MEF2B transcriptional activity, while CABIN1 mutations enhance only MEF2B transcriptional activity by impairing binding of mSin3a to CABIN1. Our data provide an unbiased identification of genetically altered genes that may play a role in the molecular pathogenesis of OAMZL and serve as therapeutic targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-26T18:10:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006632","title":"Nasal epithelial cells of PCD and non-PCD patients grown at air-liquid interface for RNAseq analysis","description":"Raw RNAseq data files of genetically unsolved PCD patients used for transcriptomic analysis aming to uplift the diagnostic rate. The non-PCD patients were used as a clinical comparator to the PCD patients. Majority of the nasal epithelial cells used for RNAseq were cultured at an air-liquid interface for 21 days, unless the data file name indicates a different air-liquid-culture time-point.","abstract":"Raw RNAseq data files of genetically unsolved PCD patients used for transcriptomic analysis aming to uplift the diagnostic rate. The non-PCD patients were used as a clinical comparator to the PCD patients. Majority of the nasal epithelial cells used for RNAseq were cultured at an air-liquid interface for 21 days, unless the data file name indicates a different air-liquid-culture time-point.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-27T08:01:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006633","title":"Identification of neoantigen from MSI-CRC patient derived organoids and its application for targeting by autologous T cells","description":"Targeting neoantigens expressed only by tumor cells enable tumor destruction without unexpected damages to healthy tissues. Here, we identified neoantigens from  microsatellite instable (MSI) colorectal cancer (CRC) patient-derived organoids by genomics and immunopeptidomics approches. The neoantigens in this study were predicted  from frame-shift mutation by whole-genome sequencing and confirmed its presentation on organoids surface class I HLA molecules by mass spectrometry. We utilized these neoantigens to isolate neoantigen-specific CD8 T cells from autologous PBMC, and proved tumor organoids killing ability of the CD8 T cells, whereas it did not attack normal organoids. This study provides a platform to identify neoantigen from patient-derived cancer organoids and a model to validate T cell recognition, which could be useful for adoptive CD8 T cell transfer treatment for MSI-CRC patient.","abstract":"Targeting neoantigens expressed only by tumor cells enable tumor destruction without unexpected damages to healthy tissues. Here, we identified neoantigens from  microsatellite instable (MSI) colorectal cancer (CRC) patient-derived organoids by genomics and immunopeptidomics approches. The neoantigens in this study were predicted  from frame-shift mutation by whole-genome sequencing and confirmed its presentation on organoids surface class I HLA molecules by mass spectrometry. We utilized these neoantigens to isolate neoantigen-specific CD8 T cells from autologous PBMC, and proved tumor organoids killing ability of the CD8 T cells, whereas it did not attack normal organoids. This study provides a platform to identify neoantigen from patient-derived cancer organoids and a model to validate T cell recognition, which could be useful for adoptive CD8 T cell transfer treatment for MSI-CRC patient.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-27T10:08:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006634","title":"Targeted_NanoSeq_Buccal_IARC","description":"Targeted NanoSeq on frozen cell pellets obtained from buccal swabs collected by IARC.","abstract":"Targeted NanoSeq on frozen cell pellets obtained from buccal swabs collected by IARC.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006635","title":"Implementation of pediatric precision oncology into clinical practice: The individualized Therapies for Children with cancer program “iTHER”","description":"iTHER is a prospective national precision oncology program aiming to define tumor molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory pediatric tumors in order to identify relevant aberrations to inform treatment.\nFrom April 2017 to April 2021, 302 samples of 253 patients were included.  Comprehensive molecular profiling utilizing lcWGS, WES, RNAseq, Affymetrix, and/or 850k methylation profiling was performed for 226 samples. Germline pathogenic variants were identified in 16% of patients. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with priority levels very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%). Diagnosis was revised or refined in 8 patients (3.5%). Spatial and temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analysis.\nOf 137 patients with follow-up beyond 12 months, 21 molecularly matched treatments were applied in 19 patients (13.9%) with modest response. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial.\niTHER demonstrates feasibility of comprehensive molecular profiling across all ages, tumor types and stages in pediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants within a clinically relevant timeframe. Therefore, WES and RNAseq is implemented into standard clinical care at the Princess Máxima Center for all children. Improved access to targeted treatments within biology-driven combination trials is required to eventually improve survival.","abstract":"iTHER is a prospective national precision oncology program aiming to define tumor molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory pediatric tumors in order to identify relevant aberrations to inform treatment.\nFrom April 2017 to April 2021, 302 samples of 253 patients were included.  Comprehensive molecular profiling utilizing lcWGS, WES, RNAseq, Affymetrix, and/or 850k methylation profiling was performed for 226 samples. Germline pathogenic variants were identified in 16% of patients. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with priority levels very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%). Diagnosis was revised or refined in 8 patients (3.5%). Spatial and temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analysis.\nOf 137 patients with follow-up beyond 12 months, 21 molecularly matched treatments were applied in 19 patients (13.9%) with modest response. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial.\niTHER demonstrates feasibility of comprehensive molecular profiling across all ages, tumor types and stages in pediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants within a clinically relevant timeframe. Therefore, WES and RNAseq is implemented into standard clinical care at the Princess Máxima Center for all children. Improved access to targeted treatments within biology-driven combination trials is required to eventually improve survival.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006636","title":"HCA_Reproductive_Tract_Adult_RNA","description":"HCA Reproductive Tract Adult RNA","abstract":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetics and genomic analysis which will include single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. Findings may be validated using in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of the cells to generate organoids (HIOs). Data dissemination: We will submit any data generated from this project to the Human Cell Atlas data coordination platform (DCP). The DCP is hosted at EMBL-EBI, providing multiple cloud platforms to host the data and data portals that will ensure rapid open access to the scientific community and opportunities to develop novel analysis tools. The HCA governance structure will ensure that uniform metadata is collected, that quality control standards are in place and that primary analysis pipelines make the data easily available for future analysis.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-28T13:56:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006637","title":"HCA_Reproductive_Tract_Adult_Spatial","description":"HCA Reproductive Tract Adult Spatial","abstract":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetics and genomic analysis which will include single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. Findings may be validated using in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of the cells to generate organoids (HIOs). Data dissemination: We will submit any data generated from this project to the Human Cell Atlas data coordination platform (DCP). The DCP is hosted at EMBL-EBI, providing multiple cloud platforms to host the data and data portals that will ensure rapid open access to the scientific community and opportunities to develop novel analysis tools. The HCA governance structure will ensure that uniform metadata is collected, that quality control standards are in place and that primary analysis pipelines make the data easily available for future analysis.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006638","title":"HCA_Gonad_Adult_RNA","description":"HCA Gonad Adult RNA","abstract":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetics and genomic analysis which will include single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. Findings may be validated using in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of the cells to generate organoids (HIOs). Data dissemination: We will submit any data generated from this project to the Human Cell Atlas data coordination platform (DCP). The DCP is hosted at EMBL-EBI, providing multiple cloud platforms to host the data and data portals that will ensure rapid open access to the scientific community and opportunities to develop novel analysis tools. The HCA governance structure will ensure that uniform metadata is collected, that quality control standards are in place and that primary analysis pipelines make the data easily available for future analysis.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006639","title":"Exome_NanoSeq__Adipose_","description":"Exome NanoSeq in adipose samples from a number of donors, including donors with and without malignancy. Samples may contain pre-malignant histology. An exome panel will be used for driver discovery.","abstract":"Investigating the driver landscape in adipose tissue.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006640","title":"HCA_Gonad_Adult_Spatial","description":"HCA Gonad Adult Spatial","abstract":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess epigenetic and transcriptomic landscape of cells. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through genetics and genomic analysis which will include single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. Findings may be validated using in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of the cells to generate organoids (HIOs). Data dissemination: We will submit any data generated from this project to the Human Cell Atlas data coordination platform (DCP). The DCP is hosted at EMBL-EBI, providing multiple cloud platforms to host the data and data portals that will ensure rapid open access to the scientific community and opportunities to develop novel analysis tools. The HCA governance structure will ensure that uniform metadata is collected, that quality control standards are in place and that primary analysis pipelines make the data easily available for future analysis.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006641","title":"Molecular profiling of DLBCL harboring a MYC-rearrangment of patients treated in the HOVON130 trial","description":"A comprehensive NGS assay for simultaneous screening of mutations, copy number alterations, and translocations provides to unique opportunity to study these molecular features in a collection of clinical samples harboring a MYC-rearrangment.","abstract":"A comprehensive NGS assay for simultaneous screening of mutations, copy number alterations, and translocations provides to unique opportunity to study these molecular features in a collection of clinical samples harboring a MYC-rearrangment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006642","title":"The clinical utility of genomics in childhood cancer extends beyond targetable mutations - Cancer Panel data","description":"We deeply sequenced 864 cancer-associated genes and the complete genomes and transcriptomes for 300 pediatric and adolescent/young adult (AYA) patients with poor prognosis or rare tumors. Using integrative somatic-germline analyses, we assessed the clinical utility of cancer genomics in this population. Clinically actionable variants were identified in 56% of patients. Improved diagnostic accuracy led to modified management in a subset. Therapeutically targetable variants, found in 54% of patients, were of unanticipated timing and type, with over 20% of these derived from the germline. Enrichment in corroborating mutational signature 3 (‘BRCAness’) in patients with germline homologous recombination defects suggests they are drivers of pediatric cancers and potential targets for PARP inhibition. Comprehensive somatic-germline cancer genomic profiling is useful at multiple points in the care trajectory for pediatric/AYA patients, supporting its integration into early clinical management. Re-biopsy at the time of relapse should be considered, and specific attention to the mutational burden is indicated. Defective DNA repair genes in the germline may represent important targetable drivers.","abstract":"We deeply sequenced 864 cancer-associated genes and the complete genomes and transcriptomes for 300 pediatric and adolescent/young adult (AYA) patients with poor prognosis or rare tumors. Using integrative somatic-germline analyses, we assessed the clinical utility of cancer genomics in this population. Clinically actionable variants were identified in 56% of patients. Improved diagnostic accuracy led to modified management in a subset. Therapeutically targetable variants, found in 54% of patients, were of unanticipated timing and type, with over 20% of these derived from the germline. Enrichment in corroborating mutational signature 3 (‘BRCAness’) in patients with germline homologous recombination defects suggests they are drivers of pediatric cancers and potential targets for PARP inhibition. Comprehensive somatic-germline cancer genomic profiling is useful at multiple points in the care trajectory for pediatric/AYA patients, supporting its integration into early clinical management. Re-biopsy at the time of relapse should be considered, and specific attention to the mutational burden is indicated. Defective DNA repair genes in the germline may represent important targetable drivers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-28T15:39:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006643","title":"Capturing sex-specific and infertility-linked effects of assisted reproductive technologies on the cord blood DNA methylome","description":"Background: Children conceived through assisted reproduction are at an increased risk for growth and genomic imprinting disorders, often linked to DNA methylation defects. It has been suggested that assisted reproductive technologies (ART) and the underlying parental infertility can induce epigenetic instability, specifically interfering with DNA methylation reprogramming events during germ cell and preimplantation development. To date, human studies exploring the association between ART and DNA methylation defects report inconsistent or inconclusive results, likely due to population heterogeneity and the use of technologies with limited coverage of the epigenome. In our study, we explore the epigenetic risk of ART by comprehensively profiling the DNA methylome of 73 human cord blood samples from singleton pregnancies (n=36 control group, n=37 ART/infertility group) from a human prospective longitudinal birth cohort, the Design, Develop, Discover (3D) Study using a high resolution sequencing based custom capture panel that interrogates over 2.4 million autosomal CpGs in the genome. \nResults: the main findings We identified striking sex-specific effects of ART on cord blood DNA methylation patterning both genome-wide and for imprinted genes. When compared to less invasive procedures such as in utero insemination, more invasive ARTs (IVF, ICSI, embryo culture) resulted in more marked and distinct effects on the cord blood DNA methylome, including targeting of loci involved in development.  \nBackground: Children conceived through assisted reproduction are at an increased risk for growth and genomic imprinting disorders, often linked to DNA methylation defects. It has been suggested that assisted reproductive technologies (ART) and the underlying parental infertility can induce epigenetic instability, specifically interfering with DNA methylation reprogramming events during germ cell and preimplantation development. To date, human studies exploring the association between ART and DNA methylation defects report inconsistent or inconclusive results, likely due to population heterogeneity and the use of technologies with limited coverage of the epigenome. In our study, we explore the epigenetic risk of ART by comprehensively profiling the DNA methylome of 73 human cord blood samples from singleton pregnancies (n=36 control group, n=37 ART/infertility group) from a human prospective longitudinal birth cohort, the Design, Develop, Discover (3D) Study, using a high resolution sequencing based custom capture panel that interrogates over 2.4 million autosomal CpGs in the genome. \nResults:  We identified striking sex-specific effects of ART on cord blood DNA methylation patterning both genome-wide and for imprinted genes. When compared to less invasive procedures such as in utero insemination, more invasive ARTs (in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), embryo culture) resulted in more marked and distinct effects on the cord blood DNA methylome, including targeting of loci involved in development.  \nConclusions: Our study highlights the ability of a sensitive, targeted, sequencing based approach to uncover DNA methylation perturbations in cord blood associated with infertility and ART and influenced by offspring sex and ART technique invasiveness.","abstract":"Background: Children conceived through assisted reproduction are at an increased risk for growth and genomic imprinting disorders, often linked to DNA methylation defects. It has been suggested that assisted reproductive technologies (ART) and the underlying parental infertility can induce epigenetic instability, specifically interfering with DNA methylation reprogramming events during germ cell and preimplantation development. To date, human studies exploring the association between ART and DNA methylation defects report inconsistent or inconclusive results, likely due to population heterogeneity and the use of technologies with limited coverage of the epigenome. In our study, we explore the epigenetic risk of ART by comprehensively profiling the DNA methylome of 73 human cord blood samples from singleton pregnancies (n=36 control group, n=37 ART/infertility group) from a human prospective longitudinal birth cohort, the Design, Develop, Discover (3D) Study using a high resolution sequencing based custom capture panel that interrogates over 2.4 million autosomal CpGs in the genome. \nResults: the main findings We identified striking sex-specific effects of ART on cord blood DNA methylation patterning both genome-wide and for imprinted genes. When compared to less invasive procedures such as in utero insemination, more invasive ARTs (IVF, ICSI, embryo culture) resulted in more marked and distinct effects on the cord blood DNA methylome, including targeting of loci involved in development.  \nBackground: Children conceived through assisted reproduction are at an increased risk for growth and genomic imprinting disorders, often linked to DNA methylation defects. It has been suggested that assisted reproductive technologies (ART) and the underlying parental infertility can induce epigenetic instability, specifically interfering with DNA methylation reprogramming events during germ cell and preimplantation development. To date, human studies exploring the association between ART and DNA methylation defects report inconsistent or inconclusive results, likely due to population heterogeneity and the use of technologies with limited coverage of the epigenome. In our study, we explore the epigenetic risk of ART by comprehensively profiling the DNA methylome of 73 human cord blood samples from singleton pregnancies (n=36 control group, n=37 ART/infertility group) from a human prospective longitudinal birth cohort, the Design, Develop, Discover (3D) Study, using a high resolution sequencing based custom capture panel that interrogates over 2.4 million autosomal CpGs in the genome. \nResults:  We identified striking sex-specific effects of ART on cord blood DNA methylation patterning both genome-wide and for imprinted genes. When compared to less invasive procedures such as in utero insemination, more invasive ARTs (in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), embryo culture) resulted in more marked and distinct effects on the cord blood DNA methylome, including targeting of loci involved in development.  \nConclusions: Our study highlights the ability of a sensitive, targeted, sequencing based approach to uncover DNA methylation perturbations in cord blood associated with infertility and ART and influenced by offspring sex and ART technique invasiveness.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-28T21:47:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006644","title":"Multi-organ landscape of therapy-resistant melanoma","description":"Metastasis and failure of present-day therapies represent the most common causes of mortality in patients with cutaneous melanoma. To identify the underlying genetic and transcriptomic landscapes, here we analyzed multi-organ metastases and tumor-adjacent tissues from eleven rapid autopsies after treatment with MAPK inhibitor (MAPKi) and/or immune checkpoint blockade (ICB) and death due to acquired resistance. Either treatment elicits shared genetic alterations that suggest immune-evasive, cross-therapy resistance mechanisms. Large, non-clustered deletions, inversions, and inter-chromosomal translocations dominate rearrangements. Using 345 therapy-naïve TCGA melanoma and 131 patient-matched melanoma pre-and-post acquired resistance to only either treatment, we performed cross-cohort analyses to identify MAPKi and ICB as respective contributors to gene amplifications and deletions enriched in autopsy versus therapy-naïve tumors. Private/late mutations and structural variants display shifted mutational and rearrangement signatures, with MAPKi specifically selecting for signatures of defective homologous-recombination, mismatch, and base-excision repair. Transcriptomic signatures and cross-talks with tumor-adjacent macroenvironments nominate organ-specific adaptive pathways. An immune-desert, CD8+-macrophage-biased archetype, T-cell exhaustion, and type-2 immunity characterize the immune contexture. This multi-organ analysis of lethal, therapy-resistant melanoma presents preliminary insights with potential to improve therapeutic strategies.","abstract":"Metastasis and failure of present-day therapies represent the most common causes of mortality in patients with cutaneous melanoma. To identify the underlying genetic and transcriptomic landscapes, here we analyzed multi-organ metastases and tumor-adjacent tissues from eleven rapid autopsies after treatment with MAPK inhibitor (MAPKi) and/or immune checkpoint blockade (ICB) and death due to acquired resistance. Either treatment elicits shared genetic alterations that suggest immune-evasive, cross-therapy resistance mechanisms. Large, non-clustered deletions, inversions, and inter-chromosomal translocations dominate rearrangements. Using 345 therapy-naïve TCGA melanoma and 131 patient-matched melanoma pre-and-post acquired resistance to only either treatment, we performed cross-cohort analyses to identify MAPKi and ICB as respective contributors to gene amplifications and deletions enriched in autopsy versus therapy-naïve tumors. Private/late mutations and structural variants display shifted mutational and rearrangement signatures, with MAPKi specifically selecting for signatures of defective homologous-recombination, mismatch, and base-excision repair. Transcriptomic signatures and cross-talks with tumor-adjacent macroenvironments nominate organ-specific adaptive pathways. An immune-desert, CD8+-macrophage-biased archetype, T-cell exhaustion, and type-2 immunity characterize the immune contexture. This multi-organ analysis of lethal, therapy-resistant melanoma presents preliminary insights with potential to improve therapeutic strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-29T13:01:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006645","title":"H3Africa - Trauma And Neurobiology: Maternal stress and transgenerational impact. Search for Epigenetic Markers","description":"This project aims to characterize the transgenerational genomic impact of genocide exposure and post-traumatic stress disorder (PTSD) in women survivors of the Rwandan genocide and their offspring.","abstract":"This project aims to characterize the transgenerational genomic impact of genocide exposure and post-traumatic stress disorder (PTSD) in women survivors of the Rwandan genocide and their offspring.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-29T13:23:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006646","title":"Follicular Lymphoma Whole Genome and Transcriptome Sequencing","description":null,"abstract":"This study includes whole genome and transcriptome sequencing of 78 follicular lymphoma tumours and WGS of matched constitutional DNA.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-29T20:24:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006647","title":"WGS_11pcw_fetus_hdbr_16154_DNA","description":"Whole genome sequencing of the developing tissues of the human fetus to understand the temporospatial pattern of clone migration and mutational processes during human development.","abstract":"Mutations act as molecular barcodes detailing the origins of the cells that compose a tissue. To generate a high resolution map of the clonal origins and migration of cells during early human development, we will perform whole genome sequencing across the extensively sampled tissues of fetuses. Furthermore, the somatic mutations will reveal in utero mutational processes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006648","title":"Integrative pan-cancer genomic and transcriptomic analyses of refractory metastatic cancer","description":null,"abstract":"A pan-cancer cohort of 1031 patients resistant to systemic therapies or with no approved therapeutic options. It includes whole-exome sequencing of 569 tumor and matched-normal samples, and transcriptome sequencing of 947 tumor samples. Biopsies were taken at entry into precision medicine trials, often after diagnosed resistance. Comprehensive clinical information is available for all patients and include patient age at biospy, tumor primary site and histological subtype, biopsy site, treatments received prior to biopsy, blood assessment results at biopsy, metastatic site at biopsy, and survival time from the biopsy date.","study_type":"Other","pubmed_ids":[36862804],"external_links":null,"is_released":true,"released_date":"2022-09-30T20:46:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006649","title":"UCSF WCDT WGS/WGBS mCRPC","description":"This dataset contains 29 paired FASTQ files from whole-genome bisulfite sequencing (WGBS) assay performed on mCRPC tumors. Sequencing was performed using 150nt paired reads generated by a Novaseq 6000 instrument. It also contains whole-genome sequencing bam files aligned to hg38 using BWA from \n36 patients, with tumor and matched tumor-adjacent normal samples. Sequencing was generated using HiSeq X Ten.","abstract":"This dataset contains 29 paired FASTQ files from whole-genome bisulfite sequencing (WGBS) assay performed on mCRPC tumors. Sequencing was performed using 150nt paired reads generated by a Novaseq 6000 instrument. It also contains whole-genome sequencing bam files aligned to hg38 using BWA from \n36 patients, with tumor and matched tumor-adjacent normal samples. Sequencing was generated using HiSeq X Ten.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-09-30T22:23:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006650","title":"Multi-regional Sequencing Analysis Reveals Extensive Genetic Heterogeneity in Gastric Tumors from Latinos","description":null,"abstract":"We evaluated gastric intratumoral heterogeneity using multi-regional sequencing of &gt;700 cancer genes in 115 tumor biopsies from 32 patients, 29 who were Latinos. We found that only ~30% of all mutations were clonal and that only 61% of the known TCGA GC drivers harbored clonal mutations. Multiple clonal mutations were found in new candidate GC drivers such as EYS, FAT4, PCDHA1, RAD50, EXO1, RECQL4, and FSIP2. The genomically stable (GS) molecular subtype, which has the worse prognosis, was identified in 48% of our Latino patients, a fraction that was &gt;2.3-fold higher than in TCGA Asian and White patients. Only a third of all tumors harbored clonal pathogenic mutations in druggable genes, with most (93%) GS tumors lacking actionable clonal mutations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006651","title":"Germline sequencing","description":"Detection of SNV/indels in the germline of pediatric cancer patients with a focus on CHEK2 germline variants. Included in this EGA upload are the parents of the children in EGA uplodad EGAD00001008763.","abstract":"Detection of SNV/indels in the germline of pediatric cancer patients with a focus on CHEK2 germline variants. Included in this EGA upload are the parents of the children in EGA uplodad EGAD00001008763.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-02T13:46:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006652","title":"Intratumoral Heterogeneity and Clonal Evolution Induced by HPV Integration.","description":"The human papillomavirus (HPV) genome is integrated into host DNA in most HPV-positive cancers, but the consequences for chromosomal integrity are unknown. Continuous long-read sequencing of oropharyngeal cancers and cancer cell lines revealed a unique form of structural variation, termed heterocateny here, characterized by heterogeneous, interrelated, and repetative patterns of concatemerized virus and host DNA segments. Evidence of heterocateny was detected in extrachromosomal and/or intrachromosomal DNA in all cases. Unique breakpoint sequences shared across structurally heterogeneous virus-host concatemers within each cancer facilitated stepwise reconstruction of their evolution from a common molecular ancestor. This analysis revealed that unstable virus and virus-host concatemers in ecDNA or integrated form mediate insertion into and excision from chromosomes, capture, rearrangement, and rolling-circle amplification of host DNA, and chromosomal rearrangements. The data indicate that heterocatena is driven by the dynamic, aberrant replication and recombination of an oncogenic DNA virus, thereby extending known consequences of HPV integration to include promotion of intra-tumoral heterogeneity and clonal evolution.","abstract":"The human papillomavirus (HPV) genome is integrated into host DNA in most HPV-positive cancers, but the consequences for chromosomal integrity are unknown. Continuous long-read sequencing of oropharyngeal cancers and cancer cell lines revealed a unique form of structural variation, termed heterocateny here, characterized by heterogeneous, interrelated, and repetative patterns of concatemerized virus and host DNA segments. Evidence of heterocateny was detected in extrachromosomal and/or intrachromosomal DNA in all cases. Unique breakpoint sequences shared across structurally heterogeneous virus-host concatemers within each cancer facilitated stepwise reconstruction of their evolution from a common molecular ancestor. This analysis revealed that unstable virus and virus-host concatemers in ecDNA or integrated form mediate insertion into and excision from chromosomes, capture, rearrangement, and rolling-circle amplification of host DNA, and chromosomal rearrangements. The data indicate that heterocatena is driven by the dynamic, aberrant replication and recombination of an oncogenic DNA virus, thereby extending known consequences of HPV integration to include promotion of intra-tumoral heterogeneity and clonal evolution.","study_type":"Other","pubmed_ids":[36715691],"external_links":null,"is_released":true,"released_date":"2022-10-02T18:43:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006653","title":"Whole genome analysis of pediatric patients with medulloblastoma","description":"Cancer genomes often contain structural variations (SVs) in non-coding regions, while its impact on tumorigenesis is still unclear. Our goal is to discover genome folding changes resulted from SVs using InfoGenomeR and InfoHiC frameworks, which may reveal novel therapeutic targets. We applied our frameworks to five pediatric patients with medulloblastoma, revealing 3D genome changes of medulloblastoma driver genes.","abstract":"Cancer genomes often contain structural variations (SVs) in non-coding regions, while its impact on tumorigenesis is still unclear. Our goal is to discover genome folding changes resulted from SVs using InfoGenomeR and InfoHiC frameworks, which may reveal novel therapeutic targets. We applied our frameworks to five pediatric patients with medulloblastoma, revealing 3D genome changes of medulloblastoma driver genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-03T00:51:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006654","title":"Genome_Wide_CRISPR_Cas9_Single_Guide_Screening_of_Cell_Models","description":"The study will perform genome-wide loss-of-function CRISPR-Cas9 screens across human cancer cell models. \n\nIncludes screening data associated with T215 research projects and R&amp;D activity.","abstract":"The goal of this project is to perform genome-wide loss-of-function CRISPR-Cas9 screens across genetically human cancer cell models to identify synthetic-lethal interactions between cancer genomes and targeted gene deletions.  These results will be used to identify novel drug targets whose inhibition is lethal to cancer cells with specific molecular alterations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006655","title":"Li_Fraumeni_Syndrome_Inheritance_and_Tumourigenesis___DupSeq","description":"This work aim to study clonal dynamics of pathogenic mutations in male germline. Using Nanoseq method, sperm from normal panel will be compared with sperm from men who have either clinical phynotypes or they have child(ren) with germline predisposition syndromes.","abstract":"Inherited cancers play a major role in about 5 to 10 percent of all cancers. It is increasingly apparent that many inherited cancer syndromes arise through new mutations acquired most likely in germline of fathers. Most of the burden of high-penetrance germline predisposition to cancer arises through mutations acquired during spermatogenesis. However, little is known about mutagenesis within the hierarchy of spermatogenesis or factors that influence rates of mutation in the testes. It is likely that mutations in spermatogonia stem cells that confer weaker selective advantage and generate smaller clonal expansions in the testes, become enrich in sperms and transmit to the next generations. However, due to the low sensitivity of standard genomic approaches, subclonal mutations that may only be present in small contiguous areas within testes have been poorly investigated.  \n\nThis proposal aims to measure the mutational burden of pathogenic variants in sperms and to identify the processes that underlie their acquisition.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006656","title":"Exome sequencing from cfDNA blood samples. 159 samples at 2x101bp Illumina reads in Fastq format.","description":"Differential presence of exons (DPE) by next generation sequencing (NGS) is a method of interpretation of whole exome sequencing. This method has been proposed to design a predictive and diagnostic algorithm with clinical value in plasma from patients bearing colorectal cancer (CRC). The aim of the present study was to determine a common exonic signature to discriminate between different clinical pictures, such as non-metastatic, metastatic and non-disease (healthy), using a sustainable and novel technology in liquid biopsy.\nThrough DPE analysis, we determined the differences in DNA exon levels circulating in plasma between patients bearing CRC vs. healthy, patients bearing CRC metastasis vs. non-metastatic and patients bearing CRC metastasis vs. healthy comparisons.  We identified a set of 510 exons (469 up and 41 down) whose differential presence in plasma allowed us to group and classify between the three cohorts. Random forest classification (machine learning) was performed and an estimated out-of-bag (OOB) error rate of 35.9% was obtained and the predictive model had an accuracy of 75% with a confidence interval (CI) of 56.6-88.5.\nIn conclusion, the DPE analysis allowed us to discriminate between different patho-physiological status such as metastatic, non-metastatic and healthy donors. In addition, this analysis allowed us to obtain very significant values with respect to previous published results, since we increased the number of samples in our study. These results suggest that circulating DNA in patient’s plasma may be actively released by cells and may be involved in intercellular communication and, therefore, may play a pivotal role in malignant transformation (genometastasis).","abstract":"Differential presence of exons (DPE) by next generation sequencing (NGS) is a method of interpretation of whole exome sequencing. This method has been proposed to design a predictive and diagnostic algorithm with clinical value in plasma from patients bearing colorectal cancer (CRC). The aim of the present study was to determine a common exonic signature to discriminate between different clinical pictures, such as non-metastatic, metastatic and non-disease (healthy), using a sustainable and novel technology in liquid biopsy.\nThrough DPE analysis, we determined the differences in DNA exon levels circulating in plasma between patients bearing CRC vs. healthy, patients bearing CRC metastasis vs. non-metastatic and patients bearing CRC metastasis vs. healthy comparisons.  We identified a set of 510 exons (469 up and 41 down) whose differential presence in plasma allowed us to group and classify between the three cohorts. Random forest classification (machine learning) was performed and an estimated out-of-bag (OOB) error rate of 35.9% was obtained and the predictive model had an accuracy of 75% with a confidence interval (CI) of 56.6-88.5.\nIn conclusion, the DPE analysis allowed us to discriminate between different patho-physiological status such as metastatic, non-metastatic and healthy donors. In addition, this analysis allowed us to obtain very significant values with respect to previous published results, since we increased the number of samples in our study. These results suggest that circulating DNA in patient’s plasma may be actively released by cells and may be involved in intercellular communication and, therefore, may play a pivotal role in malignant transformation (genometastasis).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-03T14:33:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006657","title":"Nasal brushes analysis","description":"scRNA-seq samples from healthy and asthma donors part 1.","abstract":"scRNA-seq samples from healthy and asthma donors part 1.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-03T15:45:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006658","title":"Foetal_project_WGS","description":"The aim of this experiment is to reconstruct the phylogenetic spatial organisation of an embryo.","abstract":"The aim of this experiment is to reconstruct the phylogenetic spatial organisation of an embryo.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006659","title":"Gene copy number variation in pediatric mental illness in a general population","description":"We assessed the relationship of gene copy number variation (CNV) in mental health/neurodevelopmental traits and diagnoses, physical health, and cognitive biomarkers in a community sample of 7,100 unrelated European, and East Asian children and youth (Spit for Science). Diagnoses of mental health disorders were found in 17.5% of participants and 27.6% scored in the highest 10% on either or both ADHD and OCD trait measures. Clinically relevant CNVs were present in 3.9% of participants and were associated with elevated scores on a continuous measure of ADHD (p=5.0×10-3), on a cognitive biomarker of mental health (response inhibition (p=1.0×10-2)), and on prevalence of mental disorders (p=1.9×10-6, odds ratio: 3.09). With a rise of mental illness, our data establishes a baseline for delineating genetic contributors in paediatric-onset conditions.","abstract":"We assessed the relationship of gene copy number variation (CNV) in mental health/neurodevelopmental traits and diagnoses, physical health, and cognitive biomarkers in a community sample of 7,100 unrelated European, and East Asian children and youth (Spit for Science). Diagnoses of mental health disorders were found in 17.5% of participants and 27.6% scored in the highest 10% on either or both ADHD and OCD trait measures. Clinically relevant CNVs were present in 3.9% of participants and were associated with elevated scores on a continuous measure of ADHD (p=5.0×10-3), on a cognitive biomarker of mental health (response inhibition (p=1.0×10-2)), and on prevalence of mental disorders (p=1.9×10-6, odds ratio: 3.09). With a rise of mental illness, our data establishes a baseline for delineating genetic contributors in paediatric-onset conditions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-03T17:23:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006660","title":"Persistent Mutation Burden Drives Sustained Anti-Tumor Immune Responses","description":"Tumor mutation burden is an imperfect proxy of tumor foreignness and has therefore failed to consistently demonstrate clinical utility in predicting responses in the context of immunotherapy. We evaluated mutations in regions of the genome that are unlikely to undergo loss and discovered that clonal mutations in single-copy regions and those present in multiple copies per cell constitute a persistent tumor mutation burden (pTMB) that is linked with therapeutic response to immune checkpoint blockade. Persistent mutations were retained in the context of tumor evolution under selective pressure of immunotherapy and tumors with a high pTMB content were characterized by a more inflamed tumor microenvironment. pTMB imposes an evolutionary bottleneck that cancer cells cannot overcome and may thus drive sustained immunologic tumor control in the context of immunotherapy.","abstract":"Tumor mutation burden is an imperfect proxy of tumor foreignness and has therefore failed to consistently demonstrate clinical utility in predicting responses in the context of immunotherapy. We evaluated mutations in regions of the genome that are unlikely to undergo loss and discovered that clonal mutations in single-copy regions and those present in multiple copies per cell constitute a persistent tumor mutation burden (pTMB) that is linked with therapeutic response to immune checkpoint blockade. Persistent mutations were retained in the context of tumor evolution under selective pressure of immunotherapy and tumors with a high pTMB content were characterized by a more inflamed tumor microenvironment. pTMB imposes an evolutionary bottleneck that cancer cells cannot overcome and may thus drive sustained immunologic tumor control in the context of immunotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-03T19:34:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006661","title":"scRNA-seq of patient-derived PDAC organoids and matched CAFs","description":"We established direct three-dimensional (3D) co-cultures of primary PDAC organoids and patient-matched CAFs. Single-cell RNA sequencing was performed for three organoid/CAF pairs in mono- and co-culture to uncover transcriptional changes induced by tumor-stroma interaction. Single-cell RNA sequencing data evidenced induction of a pro-inflammatory phenotype in CAFs in co-cultures. Organoids showed increased expression of genes associated with epithelial-to-mesenchymal transition (EMT) in co-cultures and several potential receptor-ligand interactions related to EMT were identified, supporting a key role of CAF-driven induction of EMT in PDAC chemoresistance.","abstract":"We established direct three-dimensional (3D) co-cultures of primary PDAC organoids and patient-matched CAFs. Single-cell RNA sequencing was performed for three organoid/CAF pairs in mono- and co-culture to uncover transcriptional changes induced by tumor-stroma interaction. Single-cell RNA sequencing data evidenced induction of a pro-inflammatory phenotype in CAFs in co-cultures. Organoids showed increased expression of genes associated with epithelial-to-mesenchymal transition (EMT) in co-cultures and several potential receptor-ligand interactions related to EMT were identified, supporting a key role of CAF-driven induction of EMT in PDAC chemoresistance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-03T23:07:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006662","title":"RNA-seq of DF149 cells – a patient-derived xenograft model of ascites-derived, homologous recombination repair-proficient, high-grade serous ovarian carcinoma – cultured in vitro and isolated after 8 hours treatment with DMSO control (3 x biological replicates) and 2.5 µM CBL0137 (3 x biological replicates)","description":"Background: High-grade serous ovarian carcinomas (HGSCs) are a heterogeneous subtype of epithelial ovarian cancers and include serous cancers arising in the fallopian tube and peritoneum. These cancers are now subdivided into homologous recombination repair (HR)-deficient and proficient subgroups as this classification impacts on management and prognosis. PARP inhibitors (PARPi) have shown significant clinical efficacy, particularly as maintenance therapy following response to platinum based chemotherapy in BRCA-mutant or homologous recombination (HR)-deficient HGSCs in both the 1st and 2nd line settings. However, PARPi have limited clinical benefit in HR-proficient HGSCs which make up almost 50% of HGSC and improving outcomes in these patients is now a high priority due to the poor prognosis with current standard of care. There are a number of potential lines of investigation including efforts in sensitizing HR-proficient tumors to PARPi. Herein, we aimed to develop a novel combination therapy by targeting SSRP1 using a small molecule inhibitor CBL0137 with PARPi in HR-proficient HGSOCs.\nExperimental design: We tested anti-cancer activity of CBL0137 monotherapy using a panel of HGSOC cell lines and patient-derived tumor cells in vitro. RNA sequencing was used to map global transcriptomic changes in CBL0137-treated patient-derived HR-proficient HGSOC cells. We tested efficacy of CBL0137 in combination with PARPi using HGSOC cell lines and patient-derived tumor cells in vitro and in vivo.\nResults: We show that SSRP1 inhibition using a small molecule, CBL0137, that traps SSRP1 onto chromatin, exerts a significant anti-growth activity in vitro against HGSC cell lines and patient-derived tumor cells, and also reduces tumor burden in vivo. CBL0137 induced DNA repair deficiency via inhibition of the HR repair pathway and sensitized SSRP1-high HR-proficient HGSC cell lines and patient-derived tumor cells/xenografts to the PARPi, Olaparib in vitro and in vivo. CBL0137 also enhanced the efficacy of DNA damaging platinum-based chemotherapy in HGSC patient-derived xenografts.\nConclusion:\nOur findings strongly suggest that combination of CBL0137 and PARP inhibition represents a novel therapeutic strategy for HR-proficient HGSCs that express high levels of SSRP1 and should be investigated in the clinic.","abstract":"Background: High-grade serous ovarian carcinomas (HGSCs) are a heterogeneous subtype of epithelial ovarian cancers and include serous cancers arising in the fallopian tube and peritoneum. These cancers are now subdivided into homologous recombination repair (HR)-deficient and proficient subgroups as this classification impacts on management and prognosis. PARP inhibitors (PARPi) have shown significant clinical efficacy, particularly as maintenance therapy following response to platinum based chemotherapy in BRCA-mutant or homologous recombination (HR)-deficient HGSCs in both the 1st and 2nd line settings. However, PARPi have limited clinical benefit in HR-proficient HGSCs which make up almost 50% of HGSC and improving outcomes in these patients is now a high priority due to the poor prognosis with current standard of care. There are a number of potential lines of investigation including efforts in sensitizing HR-proficient tumors to PARPi. Herein, we aimed to develop a novel combination therapy by targeting SSRP1 using a small molecule inhibitor CBL0137 with PARPi in HR-proficient HGSOCs.\nExperimental design: We tested anti-cancer activity of CBL0137 monotherapy using a panel of HGSOC cell lines and patient-derived tumor cells in vitro. RNA sequencing was used to map global transcriptomic changes in CBL0137-treated patient-derived HR-proficient HGSOC cells. We tested efficacy of CBL0137 in combination with PARPi using HGSOC cell lines and patient-derived tumor cells in vitro and in vivo.\nResults: We show that SSRP1 inhibition using a small molecule, CBL0137, that traps SSRP1 onto chromatin, exerts a significant anti-growth activity in vitro against HGSC cell lines and patient-derived tumor cells, and also reduces tumor burden in vivo. CBL0137 induced DNA repair deficiency via inhibition of the HR repair pathway and sensitized SSRP1-high HR-proficient HGSC cell lines and patient-derived tumor cells/xenografts to the PARPi, Olaparib in vitro and in vivo. CBL0137 also enhanced the efficacy of DNA damaging platinum-based chemotherapy in HGSC patient-derived xenografts.\nConclusion:\nOur findings strongly suggest that combination of CBL0137 and PARP inhibition represents a novel therapeutic strategy for HR-proficient HGSCs that express high levels of SSRP1 and should be investigated in the clinic.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-04T04:06:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006663","title":"BinDel: software tool for detecting clinically significant microdeletions in low-coverage WGS-based NIPT samples","description":"Clinically pathogenic chromosomal microdeletions causing genetic disorders such as DiGeorge syndrome are rare genetic aberrations that can cause clinically relevant fetal and childhood developmental deficiencies. Clinical severity of such deficiencies depend on the exact genomic location and genes affected by the fetal chromosomal aberration. \n\nHere we present the BinDel, a novel region-aware microdeletion detection software package developed to infer clinically relevant microdeletion risk in low-coverage whole-genome sequencing NIPT data. To test BinDel, we quantified the impact of sequencing coverage, fetal DNA fraction, and region length on microdeletion risk detection accuracy. We also estimated BinDel accuracy on known microdeletion samples and clinically validated aneuploidy samples. \n\nBinDel identified each positive control sample as high risk. We also determined that it is critical to take into account that the sample with a detected high microdeletion risk does not have a full chromosome aneuploidy, as the latter can cause erroneous high microdeletion risk findings. We observed that lower sequencing coverage resulted in reduced microdeletion detection accuracy, and higher fetal fractions considerably increased the microdeletion detection accuracy, with coverage becoming increasingly relevant as fetal DNA fraction decreased.\n\nIn conclusion, we developed an R package-based software tool BinDel for inferring fetal microdeletion risks, which accurately identified all positive control samples with microdeletion or -duplication aberrations as high-risk samples.","abstract":"Clinically pathogenic chromosomal microdeletions causing genetic disorders such as DiGeorge syndrome are rare genetic aberrations that can cause clinically relevant fetal and childhood developmental deficiencies. Clinical severity of such deficiencies depend on the exact genomic location and genes affected by the fetal chromosomal aberration. \n\nHere we present the BinDel, a novel region-aware microdeletion detection software package developed to infer clinically relevant microdeletion risk in low-coverage whole-genome sequencing NIPT data. To test BinDel, we quantified the impact of sequencing coverage, fetal DNA fraction, and region length on microdeletion risk detection accuracy. We also estimated BinDel accuracy on known microdeletion samples and clinically validated aneuploidy samples. \n\nBinDel identified each positive control sample as high risk. We also determined that it is critical to take into account that the sample with a detected high microdeletion risk does not have a full chromosome aneuploidy, as the latter can cause erroneous high microdeletion risk findings. We observed that lower sequencing coverage resulted in reduced microdeletion detection accuracy, and higher fetal fractions considerably increased the microdeletion detection accuracy, with coverage becoming increasingly relevant as fetal DNA fraction decreased.\n\nIn conclusion, we developed an R package-based software tool BinDel for inferring fetal microdeletion risks, which accurately identified all positive control samples with microdeletion or -duplication aberrations as high-risk samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-04T09:10:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006664","title":"Whole genome sequencing of population control samples, including 100 quartet families from Inova Health Care Services.","description":null,"abstract":"This whole genome sequence dataset of 100 quartet families (400 samples) is a population control cohort from Inova Health Care Services (Falls Church, Virginia). The samples are collected under Inova’s Study entitled “First 1000 Days of Life and Beyond”. The samples were sequenced on the NovaSeq6000 platform. The dataset will facilitate discovery of medically relevant variants for a wider variety of studies in human disease and health by helping to further catalogue variation in control populations, and also to establish baseline tempo and modes of mutation. No similar dataset yet exists and research studies are being restricted because of this.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001006665","title":"single-cell RNA-Seq of colorectal cancer patient samples","description":null,"abstract":"We describe in a prospective cohort a novel CD8+ T effector memory population, which is characterized by high levels of Granzyme K (GZMK high CD8+ TEM) and correlated with CD15 high tumor infiltrating neutrophils. In this context, we performed single-cell RNA-Seq analysis on matched tumor and non-tumor adjacent unsorted tissues to define a gene signature of GZMK high CD8+ TEM. This was associated with worse prognosis on a larger independent cohort of CRC patients and of lung cancer (TCGA).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-05T12:27:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006666","title":"bulk RNA-Seq of colorectal cancer patient samples","description":null,"abstract":"Association between microbes and cancer has been reported repeatedly; however, it is not clear if molecular tumour properties are connected to specific microbial colonization patterns. This is due mainly to the current technical and analytical strategy limitations to characterise tumour-associated bacteria. Here, we propose an approach to detect bacterial signals in human RNA sequencing data and associate them with the clinical and molecular properties of the tumours. The method was tested on public datasets from The Cancer Genome Atlas and its accuracy was assessed on a new cohort of colorectal cancer patients. Our analysis shows that intratumoral microbiome composition is correlated with survival, anatomic location, microsatellite instability, consensus molecular subtype and immune cell infiltration in colon tumours. In particular, we find Faecalibacterium prausnitzii, Coprococcus comes, Bacteroides spp., Fusobacterium spp. and Clostridium spp. to be strongly associated with tumour properties. We implemented an approach to analyse concurrently clinical and molecular properties of the tumour and the composition of the associated microbiome. Our results may improve patient stratification and pave the path for mechanistic studies on microbiota-tumour crosstalk.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-05T12:46:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006667","title":"GermCellTumour_WGMS","description":"DNA and RNA sequencing across a number of different germ cell tumours, included mixed components within the same tumour.","abstract":"This study aims to characterise the genetic and transcriptomic profile of germ cell tumours, in particular to develop a phylogenetic tree within mixed germ cell tumours to provide insight into their development and cell of origin, both of which are currently poorly understood.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006668","title":"Whole genome sequencing of population control dataset of 100 quartet families","description":null,"abstract":"This whole genome sequence dataset of 100 quartet families (400 samples) is a population control cohort from Inova Health Care Services (Falls Church, Virginia). The samples are collected under Inova’s Study entitled “First 1000 Days of Life and Beyond”. The samples were sequenced on the NovaSeq6000 platform. The dataset will facilitate discovery of medically relevant variants for a wider variety of studies in human disease and health by helping to further catalogue variation in control populations, and also to establish baseline tempo and modes of mutation.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006669","title":"Molecular biomarkers in progression from refractory celiac disease to the lethal cancer variety enteropathy associated T cell lymphoma (EATL)","description":"Enteropathy associated T cell lymphoma (EATL) is frequently preceded by a state of refractoriness to the gluten-free diet, called “refractory celiac disease” or RCD. We aim to study which mutations and copy number aberrations are already manifest in RCD and to identify differences between RCD patients that do, and do not, develop EATL. We have applied whole exome sequencing to detect mutations and copy number aberration predictive for progression from RCD to EATL.","abstract":"Enteropathy associated T cell lymphoma (EATL) is frequently preceded by a state of refractoriness to the gluten-free diet, called “refractory celiac disease” or RCD. We aim to study which mutations and copy number aberrations are already manifest in RCD and to identify differences between RCD patients that do, and do not, develop EATL. We have applied whole exome sequencing to detect mutations and copy number aberration predictive for progression from RCD to EATL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-02-21T13:05:31.914974+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006670","title":"DNA methylation landscape of prostate cancer","description":"Metastases from primary prostate cancers to rare locations, such as the brain, are becoming more common due to longer life expectancy thanks to improved treatments. Epigenetic dysregulation is a feature of primary prostate cancer, and distinct DNA methylation profiles are associated with the mutually exclusive SPOP mutant or TMPRSS2-ERG fusion genetic backgrounds. Using a cohort of 42 patients with prostate cancer brain metastases (PCBM), with matched primary samples available for 17 patients, we carried out DNA methylation analysis using Illumina EPIC array. We examined the epigenetic distinction between primary PCa and PCBM, the association between epigenetic alterations and mutational background, and particular epigenetic alterations that may be associated with PCBM in particular. Multiregion sampling of PCBM revealed epigenetic heterogeneity in metastases. We found aberrant methylation in PCBM is associated with mutational background, PRC2 complex activity and upregulation of EZH2, an effect that is particularly pronounced in SPOP mutant PCBM. While we detected a hypermethylator phenotype in PCBM, we also observed hypomethylation occurring at the promoters of genes involved in neuroactive ligand-receptor interactions or the calcium signalling pathway, such as GABRB3 and GRM5, a change not observed in non-brain prostate cancer metastases.","abstract":"Metastases from primary prostate cancers to rare locations, such as the brain, are becoming more common due to longer life expectancy thanks to improved treatments. Epigenetic dysregulation is a feature of primary prostate cancer, and distinct DNA methylation profiles are associated with the mutually exclusive SPOP mutant or TMPRSS2-ERG fusion genetic backgrounds. Using a cohort of 42 patients with prostate cancer brain metastases (PCBM), with matched primary samples available for 17 patients, we carried out DNA methylation analysis using Illumina EPIC array. We examined the epigenetic distinction between primary PCa and PCBM, the association between epigenetic alterations and mutational background, and particular epigenetic alterations that may be associated with PCBM in particular. Multiregion sampling of PCBM revealed epigenetic heterogeneity in metastases. We found aberrant methylation in PCBM is associated with mutational background, PRC2 complex activity and upregulation of EZH2, an effect that is particularly pronounced in SPOP mutant PCBM. While we detected a hypermethylator phenotype in PCBM, we also observed hypomethylation occurring at the promoters of genes involved in neuroactive ligand-receptor interactions or the calcium signalling pathway, such as GABRB3 and GRM5, a change not observed in non-brain prostate cancer metastases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-07T10:18:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006671","title":"Targeted mutational profiling of circulating tumor DNA and matched tissue biopsies in high grade serous ovarian cancer patients","description":null,"abstract":"This study analyzed the mutational landscape (65 genes) of high grade serous ovarian cancer (HGS-EOC) over time. We used 18 patients from a previously published study (Paracchini et al., Clinical Cancer Res, 2021), and investigated somatic variants in tissue samples (33 biopsies) and in matched circulating tumor DNA (ctDNA) extracted from matched plasma samples at up to three different time points (43 plasma samples in total). The presence and the nature of the variants were evaluated in the tissue samples and over time (in ctDNA) for each patient.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006672","title":"Generation of two gene edited iPSC-lines carrying a DOX-inducible NGN2 expression cassette with and without GFP in the AAVS1 locus","description":null,"abstract":"The neuronal transcription factor NGN2 (Neurog2) can convert stem cells into functional neurons quickly and efficiently. In this study, two human induced pluripotent stem cell (iPSC) lines were engineered (from the parental line BIONi010-C) to contain DOX-inducible constructs of NGN2 either with or without T2a-eGFP into the safe-harbour locus AAVS1. The two cell lines, BIONi010-C-13 and BIONi010-C-15, respectively, remain pluripotent without DOX but differentiate to (GFP-positive) neurons when DOX is added without the need for differentiation factors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006673","title":"WGS of Basal Cell Carcinoma of skin reveals distinct mutational landscape and the role of HIPPO-YAP pathway in disease progression.","description":null,"abstract":"Basal Cell Carcinoma (BCC) is the commonest type of skin cancer which has not been yet studied by whole genome sequencing (WGS). We have assembled the largest to date BCC cohort representing major histological subtypes for genetic analysis by WGS (89), WES (310) and RNAseq (360).\nMutational profile in BCC is due to UV-light exposure, however it differs from melanoma by high fraction of COSMIC signature SBS7b mutations. We explained it by high contribution to mutagenesis in BCC of GC-rich early replicating regions, which in BCC are characterized by more condensed and difficult to repair chromatin. We report that loss of TP53 is the first event in BCC and precedes the loss of PTCH1. Moreover, we deduce from 17p copy neutral LOH regions that loss of TP53 results in a dramatic increase of mutation rates in BCC. In line with that BCC with TP53 mutations have 2.5-fold higher mutation burden than BCC with wt-TP53. We discovered novel BCC driver genes outside the Hh pathway. 65% of BCC harbor mutations in HIPPO-YAP and Contact Inhibition of Proliferation pathways: (FAT1(30%), NF2(9%), ARHGAP35(18%), CREBBP(21%), PTPN14(21%), LATS1(9%)). We validated the role of these genes in BCC cell line by siRNA screening followed by migration and proliferation assays. Promoter mutations of TERT were identified in 48% of BCC and resulted in its overexpression. High-risk morpheaform BCCs were different from low-risk BCCs by activation of HIPPO-YAP pathway and fibrotic types of tumor microenvironment. BCC with intrinsic resistance to vismodegib demonstrated a hyperactivation of HIPPO-YAP pathway.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006674","title":"Follicular lymphoma at diagnosis, treated in first line with immunochemotherapy","description":"We performed targeted NGS in Follicular lymphoma samples at diagnosis. Explored clinico-genetic correlations and assessed four clinical or clinicogenetic risk models (FLIPI, FLIPI-2, PRIMA-IP or m7-FLIPI-molecular score)  in patients with symptomatic FL who received frontline immunochemotherapy. Out of 191 patients with FL grade 1-3a, 109 were successfully genotyped. Treatment consisted on rituximab (R) plus CVP/CHOP (72.5%) or R-bendamustine (R-B) (27.5%).","abstract":"We performed targeted NGS in Follicular lymphoma samples at diagnosis. Explored clinico-genetic correlations and assessed four clinical or clinicogenetic risk models (FLIPI, FLIPI-2, PRIMA-IP or m7-FLIPI-molecular score)  in patients with symptomatic FL who received frontline immunochemotherapy. Out of 191 patients with FL grade 1-3a, 109 were successfully genotyped. Treatment consisted on rituximab (R) plus CVP/CHOP (72.5%) or R-bendamustine (R-B) (27.5%).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-10T08:35:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006675","title":"T cell responses of ALS patients","description":"In this project, we aimed to understand how T cell responses contribute to the disease progression of amyotrophic lateral sclerosis (ALS). The present data is on single-cell sequencing isolated from human cerebrospinal fluid (CSF) cells from both ALS patients (n=5) and controls (n=4). This analysis was conducted as part of a bigger project which is summarized in the section below.\n\nWe used flow cytometry to define T cell subsets and phenotypes in blood and CSF samples collected at the time of diagnosis on a cohort of 89 newly diagnosed ALS patients in Stockholm, Sweden. High frequency of CD4+FOXP3- effector T cells in blood and CSF was associated with poor survival whereas high frequency of activated regulatory T (Treg) cells and high ratio between activated and resting Treg cells in blood was associated with better survival. T cell profiles also predicted disease progression rate. On an independent cohort of cases and controls, we used single cell transcriptomics data to demonstrate that ALS patients had altered T cell gene expression patterns and clonally expanded CD4+ and CD8+ T cells in CSF. In summary, T cell responses contribute to disease progression of ALS, supporting modulation of adaptive immunity as a viable therapeutic option.","abstract":"In this project, we aimed to understand how T cell responses contribute to the disease progression of amyotrophic lateral sclerosis (ALS). The present data is on single-cell sequencing isolated from human cerebrospinal fluid (CSF) cells from both ALS patients (n=5) and controls (n=4). This analysis was conducted as part of a bigger project which is summarized in the section below.\n\nWe used flow cytometry to define T cell subsets and phenotypes in blood and CSF samples collected at the time of diagnosis on a cohort of 89 newly diagnosed ALS patients in Stockholm, Sweden. High frequency of CD4+FOXP3- effector T cells in blood and CSF was associated with poor survival whereas high frequency of activated regulatory T (Treg) cells and high ratio between activated and resting Treg cells in blood was associated with better survival. T cell profiles also predicted disease progression rate. On an independent cohort of cases and controls, we used single cell transcriptomics data to demonstrate that ALS patients had altered T cell gene expression patterns and clonally expanded CD4+ and CD8+ T cells in CSF. In summary, T cell responses contribute to disease progression of ALS, supporting modulation of adaptive immunity as a viable therapeutic option.","study_type":"Other","pubmed_ids":[36347843],"external_links":null,"is_released":true,"released_date":"2022-10-10T08:38:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006676","title":"DERMATLAS__Myopericytoma","description":"IVirtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are myopericytomas.","abstract":"IVirtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are myopericytomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-10T10:04:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006677","title":"The_saliva_microbiome_using_nanopore_sequencing","description":"This study aims to access the quality of the microbiome using Nanopore Q20+ sequencing of saliva microbiome.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The aim of this project is to pilot a method to identify novel transposable elements that carry antimicrobial resistance genes and the species they belong to from whole genome sequencing of mixed microbial saliva samples. Currently, a bioinformatics tool has been developed to identify novel insertion sequences from short-read metagenomes, but the short-read nature of this data limits the ability of repeat regions (of insertion sequences) to be resolved and genetic elements to be linked to species from their assemblies. Nanopore can counteract this by providing longer reads that span larger regions of the genome.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006678","title":"Longitudinal evaluation of serum microRNAs as biomarkers for neuroblastoma burden and therapeutic p53 reactivation","description":"Accurate assessment of treatment response and residual disease is indispensable for the evaluation of cancer treatment efficacy. However, performing tissue biopsies for longitudinal follow-up poses a major challenge in the management of solid tumours like neuroblastoma. In the present study, we evaluated whether circulating miRNAs are suitable to monitor neuroblastoma tumour burden and whether treatment-induced changes of miRNA abundance in the tumour are detectable in serum. We performed small RNA sequencing on longitudinally collected serum samples from mice carrying orthotopic neuroblastoma xenografts that were exposed to treatment with idasanutlin or temsirolimus. We identified 57 serum miRNAs to be differentially expressed upon xenograft tumour manifestation, out of which 21 were also found specifically expressed in the serum of human high-risk neuroblastoma patients. The murine serum levels of these 57 miRNAs correlated with tumour tissue expression and tumour volume, suggesting potential utility for monitoring tumour burden. In addition, we describe serum miRNAs that dynamically respond to p53 activation following treatment of engrafted mice with idasanutlin. We identified idasanutlin-induced serum miRNA expression changes upon one day and 11 days of treatment. By limiting to miRNAs with a tumour-related induction, we put forward hsa-miR-34a-5p as a potential pharmacodynamic biomarker of p53 activation in serum.","abstract":"Accurate assessment of treatment response and residual disease is indispensable for the evaluation of cancer treatment efficacy. However, performing tissue biopsies for longitudinal follow-up poses a major challenge in the management of solid tumours like neuroblastoma. In the present study, we evaluated whether circulating miRNAs are suitable to monitor neuroblastoma tumour burden and whether treatment-induced changes of miRNA abundance in the tumour are detectable in serum. We performed small RNA sequencing on longitudinally collected serum samples from mice carrying orthotopic neuroblastoma xenografts that were exposed to treatment with idasanutlin or temsirolimus. We identified 57 serum miRNAs to be differentially expressed upon xenograft tumour manifestation, out of which 21 were also found specifically expressed in the serum of human high-risk neuroblastoma patients. The murine serum levels of these 57 miRNAs correlated with tumour tissue expression and tumour volume, suggesting potential utility for monitoring tumour burden. In addition, we describe serum miRNAs that dynamically respond to p53 activation following treatment of engrafted mice with idasanutlin. We identified idasanutlin-induced serum miRNA expression changes upon one day and 11 days of treatment. By limiting to miRNAs with a tumour-related induction, we put forward hsa-miR-34a-5p as a potential pharmacodynamic biomarker of p53 activation in serum.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-10T14:09:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006679","title":"Identification of genomic aberrations in low-grade serous ovarian cancer","description":"Low-grade serous ovarian cancer (LGSOC) is a rare disease that occurs more frequently in younger women compared with high-grade disease. The current treatment is suboptimal, and better understanding of molecular pathogenesis of this disease is needed. In this study, we compared the whole genome sequences of LGSOCs from short-term and long-term survivors (defined as &lt;40 and &gt;60 months, respectively). Our goal was to identify novel genomic aberrations  in LGSOC, especially in short-term survivors.","abstract":"Low-grade serous ovarian cancer (LGSOC) is a rare disease that occurs more frequently in younger women compared with high-grade disease. The current treatment is suboptimal, and better understanding of molecular pathogenesis of this disease is needed. In this study, we compared the whole genome sequences of LGSOCs from short-term and long-term survivors (defined as &lt;40 and &gt;60 months, respectively). Our goal was to identify novel genomic aberrations  in LGSOC, especially in short-term survivors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-10T15:11:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006680","title":"Advanced molecular neuropathology to increase diagnostic accuracy in pediatric neurooncology","description":"To assess their utility in routine neuropathology, we prospectively integrated DNA methylation-based CNS tumor classification and targeted gene panel sequencing of tumor and constitutional DNA with blinded neuropathological reference diagnostics for a population-based cohort of &gt; 1,200 newly-diagnosed pediatric patients.","abstract":"To assess their utility in routine neuropathology, we prospectively integrated DNA methylation-based CNS tumor classification and targeted gene panel sequencing of tumor and constitutional DNA with blinded neuropathological reference diagnostics for a population-based cohort of &gt; 1,200 newly-diagnosed pediatric patients.","study_type":"Other","pubmed_ids":[36928815],"external_links":null,"is_released":true,"released_date":"2022-10-12T08:53:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006681","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__AA_study_UTC","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, head and neck, bladder, gall bladder, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \n\nThis sub-project will specifically investigate aristolochic exposure in Europe.\n\nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, head and neck, bladder, gall bladder, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \n\nThis sub-project will specifically investigate aristolochic exposure in Europe.\n\nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006682","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__AA_study_RCC","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, head and neck, bladder, gall bladder, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \n\nThis sub-project will specifically investigate aristolochic exposure in Europe.\n\nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, head and neck, bladder, gall bladder, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \n\nThis sub-project will specifically investigate aristolochic exposure in Europe.\n\nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006683","title":"Res1_H23_exp2_MC_13_07_22","description":"8 samples are cell pellets for genomic DNA extraction.\nCRISPR PCR1 and PCR2 indexing - Please use standard Kosuke primers.","abstract":"8 samples are cell pellets for genomic DNA extraction.\nCRISPR PCR1 and PCR2 indexing - Please use standard Kosuke primers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-12T16:48:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006684","title":"DERMATLAS__Myopericytoma_RNAseq","description":"IVirtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are myopericytomas.","abstract":"IVirtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are myopericytomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-12T16:49:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006685","title":"DERMATLAS__Tubular_adenoma_RNAseq","description":"IVirtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are tubular adenomas.","abstract":"IVirtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are tubular adenomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-12T16:50:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006686","title":"DERMATLAS__Tubular_adenoma","description":"IVirtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are tubular adenomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are tubular adenomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-12T16:50:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006687","title":"IBD_associated_dysplasia","description":"Our cohort consists of patients with Inflammatory Bowel Disease (IBD)-associated dysplasia of the colorectal epithelium.  All cases have follow-up neoplastic lesions at the same location which have either progressed to a higher grade of dysplasia/carcinoma (progressors) or which have remained at the same grade of dysplasia (non-progressors).  Genomic sequencing of this cohort will allow a comprehensive analysis of the mutational landscape and other changes of different grades of IBD-associated dysplasia, comparing progressors with non-progressors.  The key research questions are:\n-\tWhat genetic and genomic changes occur at the pre-cancer stage (in IBD associated colorectal neoplasia) and do these differ between progressor and non-progressor cases?  \n-\tAre any of these changes more common in the precursor specimens of the progressor cohort compared with the non-progressor cohort and could such changes potentially help predict which cases of dysplasia are at higher risk of progressing.","abstract":"Our cohort consists of patients with Inflammatory Bowel Disease (IBD)-associated dysplasia of the colorectal epithelium.  All cases have follow-up neoplastic lesions at the same location which have either progressed to a higher grade of dysplasia/carcinoma (progressors) or which have remained at the same grade of dysplasia (non-progressors).  Genomic sequencing of this cohort will allow a comprehensive analysis of the mutational landscape and other changes of different grades of IBD-associated dysplasia, comparing progressors with non-progressors.  The key research questions are:\n-\tWhat genetic and genomic changes occur at the pre-cancer stage (in IBD associated colorectal neoplasia) and do these differ between progressor and non-progressor cases?  \n-\tAre any of these changes more common in the precursor specimens of the progressor cohort compared with the non-progressor cohort and could such changes potentially help predict which cases of dysplasia are at higher risk of progressing.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006688","title":"Tocilizumab treatment leads to early resolution of myeloid dysfunction and lymphopenia in patients hospitalized with COVID-19","description":"Tocilizumab, an anti-interleukin-6 receptor inhibitor, is recommended in global treatment guidelines for patients hospitalized with severe COVID-19. Using proteomic and transcriptomic analysis, we characterized the immune profile and identified cellular and molecular pathways directly modified by tocilizumab in peripheral blood samples collected from patients enrolled in the COVACTA study, a phase 3, randomized, double-blind, placebo-controlled trial, to assess the efficacy and safety of tocilizumab in hospitalized patients with severe COVID-19 pneumonia. We identified factors predicting disease severity and clinical outcomes, including markers of inflammation, lymphopenia, myeloid dysfunction, and organ injury. Proteomic analysis confirmed a pharmacodynamic effect for tocilizumab. Transcriptomic analysis revealed that tocilizumab treatment leads to faster resolution of lymphopenia and myeloid dysfunction associated with severe COVID-19 thus supporting an underlying anti-inflammatory mechanism of action for the beneficial effects of tocilizumab in patients hospitalized with COVID-19.","abstract":"Tocilizumab, an anti-interleukin-6 receptor inhibitor, is recommended in global treatment guidelines for patients hospitalized with severe COVID-19. Using proteomic and transcriptomic analysis, we characterized the immune profile and identified cellular and molecular pathways directly modified by tocilizumab in peripheral blood samples collected from patients enrolled in the COVACTA study, a phase 3, randomized, double-blind, placebo-controlled trial, to assess the efficacy and safety of tocilizumab in hospitalized patients with severe COVID-19 pneumonia. We identified factors predicting disease severity and clinical outcomes, including markers of inflammation, lymphopenia, myeloid dysfunction, and organ injury. Proteomic analysis confirmed a pharmacodynamic effect for tocilizumab. Transcriptomic analysis revealed that tocilizumab treatment leads to faster resolution of lymphopenia and myeloid dysfunction associated with severe COVID-19 thus supporting an underlying anti-inflammatory mechanism of action for the beneficial effects of tocilizumab in patients hospitalized with COVID-19.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-13T00:40:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006689","title":"Genomic and ecologic characteristics of the airway microbial-mucosal complex","description":"Lung diseases due to infection and dysbiosis affect hundreds of millions of people world-wide. Microbial communities at the airway mucosal barrier are conserved and highly ordered, reflecting symbiosis and co-evolution with human host factors. We show here the results of the first systematic culture and whole-genome sequencing of the principal airway bacterial species. We match the gene content of bacterial isolates to human transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways that can sustain host interactions with the microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosal immunity in lung diseases of global significance.","abstract":"Lung diseases due to infection and dysbiosis affect hundreds of millions of people world-wide. Microbial communities at the airway mucosal barrier are conserved and highly ordered, reflecting symbiosis and co-evolution with human host factors. We show here the results of the first systematic culture and whole-genome sequencing of the principal airway bacterial species. We match the gene content of bacterial isolates to human transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways that can sustain host interactions with the microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosal immunity in lung diseases of global significance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-13T10:12:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006690","title":"RNA seq before and after cold pressor test","description":"The cold pressor test (CPT) is a widely used pain provocation test to investigate both pain tolerance and cardiovascular responses. Twenty-two females were phenotypically assessed before and after a CPT, and blood samples were taken for RNA-sequencing.","abstract":"The cold pressor test (CPT) is a widely used pain provocation test to investigate both pain tolerance and cardiovascular responses. Twenty-two females were phenotypically assessed before and after a CPT, and blood samples were taken for RNA-sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-13T11:41:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006691","title":"Molecular biomarkers for stratification periheral T cell lymphoma","description":"Peripheral T cell lymphoma (PTCL) is a diverse group of rare lymphoid malignancies with overall poor prognosis. Diverse biological mchanisms behind these diverse disease groups make targeted treatment challenging.\nBased on molecular biomarkers, more , the aim is to characterise more specific features for the different clinically defined PTCL for new future prognostic therapies.","abstract":"Peripheral T cell lymphoma (PTCL) is a diverse group of rare lymphoid malignancies with overall poor prognosis. Diverse biological mchanisms behind these diverse disease groups make targeted treatment challenging.\nBased on molecular biomarkers, more , the aim is to characterise more specific features for the different clinically defined PTCL for new future prognostic therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-01-22T08:29:13.696784+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006692","title":"Pre-neoplastic liver colonization by 11p15.5 altered mosaic cells in young children with hepatoblastoma","description":"In children, liver tumors are a heterogeneous group representing 1-2% of all cancers with the most common diagnosis being hepatoblastoma (HB). While HBs are predominantly sporadic, around 15% of cases develop as part of predisposition syndromes such as familial adenomatous polyposis (APC mutation) or Beckwith-Wiedemann (BWS; 11p15.5 locus altered). Here, we identified a mosaic genetic alteration of 11p15.5 locus in the liver in 17% of HB patients without a clinical diagnosis of BWS syndrome. These mosaic 11p15.5 alterations were never found in children with other types of liver tumor (hepatocellular carcinoma or adenoma, fibrolamellar carcinoma). Bulk transcriptomic analysis revealed the abundance of extracellular matrix, angiogenesis, and progenitor gene signatures in mosaic livers. In situ hybridization assay RNAscope allowed for the detection of 11p15.5 altered hepatocytes mosaicism in liver FFPE sections of HB patients presenting IGF2 overexpression and H19 downregulation together with an alteration of the zonal architecture of the liver. Spatial transcriptomics analysis revealed an overexpression of the IGF2 pathway, lipogenesis, and platelet activation in 11p15.5 altered hepatocytes. These data provide insights for 11p15.5 mosaicism detection as well as functional consequences of these alterations during the early steps of carcinogenesis.","abstract":"In children, liver tumors are a heterogeneous group representing 1-2% of all cancers with the most common diagnosis being hepatoblastoma (HB). While HBs are predominantly sporadic, around 15% of cases develop as part of predisposition syndromes such as familial adenomatous polyposis (APC mutation) or Beckwith-Wiedemann (BWS; 11p15.5 locus altered). Here, we identified a mosaic genetic alteration of 11p15.5 locus in the liver in 17% of HB patients without a clinical diagnosis of BWS syndrome. These mosaic 11p15.5 alterations were never found in children with other types of liver tumor (hepatocellular carcinoma or adenoma, fibrolamellar carcinoma). Bulk transcriptomic analysis revealed the abundance of extracellular matrix, angiogenesis, and progenitor gene signatures in mosaic livers. In situ hybridization assay RNAscope allowed for the detection of 11p15.5 altered hepatocytes mosaicism in liver FFPE sections of HB patients presenting IGF2 overexpression and H19 downregulation together with an alteration of the zonal architecture of the liver. Spatial transcriptomics analysis revealed an overexpression of the IGF2 pathway, lipogenesis, and platelet activation in 11p15.5 altered hepatocytes. These data provide insights for 11p15.5 mosaicism detection as well as functional consequences of these alterations during the early steps of carcinogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-13T14:45:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006693","title":"Whole Genome Sequences of 18th century African descended individuals from Charleston, South Carolina.","description":"This study presents Whole Genome Sequencing results from the Anson Street African Burial Ground Project, which is a community-based initiative aimed at understanding the histories of  37 Ancestors found during construction in Charleston, South Carolina. Here we report fastq files for all 37 Ancestors. DNA was extracted at the University of Tennessee-Knoxville following Dabney et al. 2013, and dual index libraries prepared using a modified NEBNext Ultra II kit with partial USER enzyme digestion. Libraries were then enriched for human genomic DNA (MyBaits) and sequenced on Illumina Platforms.","abstract":"This study presents Whole Genome Sequencing results from the Anson Street African Burial Ground Project, which is a community-based initiative aimed at understanding the histories of  37 Ancestors found during construction in Charleston, South Carolina. Here we report fastq files for all 37 Ancestors. DNA was extracted at the University of Tennessee-Knoxville following Dabney et al. 2013, and dual index libraries prepared using a modified NEBNext Ultra II kit with partial USER enzyme digestion. Libraries were then enriched for human genomic DNA (MyBaits) and sequenced on Illumina Platforms.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-13T15:45:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006694","title":"Single-cell atlas of multiple myeloma and precursor diseases","description":"Single cell profiling of small cohorts of myeloma precursor disease patient samples including monoclonal gammopathy of unknown significance and smoldering multiple myeloma have shown diverse evolutionary patterns and immune changes that occur early in the disease process. Using scRNAseq and scBCRseq in a large cohort of fifty-three patients with myeloma precursor disease in comparison with myeloma and normal donors we describe the early genomic drivers of malignant transformation and describe their divergent clonal expansion in hyperdiploid compared to non-hyperdiploid samples. We describe intra-patient heterogeneity with potential therapeutic implications as well as the distinct evolution patterns (linear/branching) from myeloma precursor disease to myeloma. Finally, we describe the unique adaptations of the microenvironment as a response to distinct genomic changes in myeloma cells. These results further our knowledge to characterize myeloma precursor disease evolution, inform individual patient progression risk stratification and identify potential biomarkers that could be clinically exploited.","abstract":"Single cell profiling of small cohorts of myeloma precursor disease patient samples including monoclonal gammopathy of unknown significance and smoldering multiple myeloma have shown diverse evolutionary patterns and immune changes that occur early in the disease process. Using scRNAseq and scBCRseq in a large cohort of fifty-three patients with myeloma precursor disease in comparison with myeloma and normal donors we describe the early genomic drivers of malignant transformation and describe their divergent clonal expansion in hyperdiploid compared to non-hyperdiploid samples. We describe intra-patient heterogeneity with potential therapeutic implications as well as the distinct evolution patterns (linear/branching) from myeloma precursor disease to myeloma. Finally, we describe the unique adaptations of the microenvironment as a response to distinct genomic changes in myeloma cells. These results further our knowledge to characterize myeloma precursor disease evolution, inform individual patient progression risk stratification and identify potential biomarkers that could be clinically exploited.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-14T00:34:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006695","title":"Tissue DNA, WBC DNA and cfDNA (deep-)sequencing of mCRC patients treated with doublet chemotherapy and anti-EGFR in the CAIRO5 study","description":"This study assessed whether ctDNA based treatment response monitoring could be performed in a tumor tissue-independent manner by combining ultra-deep targeted sequencing analyses of cfDNA with patient-matched white blood cell (WBC) derived DNA. In total, 183 cfDNA and 49 WBC samples, along with 28 tissue samples, from 52 metastatic colorectal cancer patients participating in the prospective phase III CAIRO5 clinical trial (NCT02162563) were analyzed using the PGDx elio plasma resolve assay.","abstract":"This study assessed whether ctDNA based treatment response monitoring could be performed in a tumor tissue-independent manner by combining ultra-deep targeted sequencing analyses of cfDNA with patient-matched white blood cell (WBC) derived DNA. In total, 183 cfDNA and 49 WBC samples, along with 28 tissue samples, from 52 metastatic colorectal cancer patients participating in the prospective phase III CAIRO5 clinical trial (NCT02162563) were analyzed using the PGDx elio plasma resolve assay.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-17T11:19:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006696","title":"Shallow sequencing of organoid/xenograft or human colorectal metastases","description":null,"abstract":"Bank of metastatic colorectal cancer Organoids and Xenografts","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-17T13:26:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006697","title":"Targeted Sequencing Xenturion","description":null,"abstract":"Targeted sequencing of paired organoids and xenografts from colorectal cancer metastasis","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-17T16:47:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006698","title":"Characterization of chromatin accessibility in metastatic prostate cancer","description":"The development of resistance to second-generation AR-signaling inhibitors (ARSIs) and progression to metastatic castrate-resistant prostate cancer (mCRPC) represents a huge obstacle to the improvement of patients’ clinical outcomes. Lineage plasticity is a common mechanism that drives the development of mCRPC by changing chromatin conformation at regulatory elements affecting downstream gene activity. ATAC-seq is a popular technique that measures accessible chromatin regions. To better understand of potential epigenomic mechanisms of ARSI resistance in prostate cancer, in this study, we performed ATAC-seq on 70 mCRPC tissue biopsies from the SU2C/PCF West Coast Dream Team (WCDT) cohort.","abstract":"The development of resistance to second-generation AR-signaling inhibitors (ARSIs) and progression to metastatic castrate-resistant prostate cancer (mCRPC) represents a huge obstacle to the improvement of patients’ clinical outcomes. Lineage plasticity is a common mechanism that drives the development of mCRPC by changing chromatin conformation at regulatory elements affecting downstream gene activity. ATAC-seq is a popular technique that measures accessible chromatin regions. To better understand of potential epigenomic mechanisms of ARSI resistance in prostate cancer, in this study, we performed ATAC-seq on 70 mCRPC tissue biopsies from the SU2C/PCF West Coast Dream Team (WCDT) cohort.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-17T20:16:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006699","title":"Clonal dynamics of human embryonic stem cells","description":null,"abstract":"We performed long-term culture and whole-genome sequencing for cell lines of human embryonic stem cells to investigate the genomic stability and conal dynamics during cultures.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006700","title":"Plasma DNA end analysis (mouse)","description":"Plasma DNA end analysis (mouse)","abstract":"Plasma DNA end analysis (mouse)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-18T06:52:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006701","title":"Cell-free DNA cleavages analysis (human)","description":"Cell-free DNA cleavages analysis (human)","abstract":"Cell-free DNA cleavages analysis (human)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-18T06:53:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006702","title":"Characterization of MCSP+ melanoma DCC and MelDCC lines","description":"To dissect the sequence of genotypic and phenotypic progression during early metastatic colonization, we searched for the earliest detectable disseminated cancer cells (DCC) and identified MCSP+ melanoma cells as strong candidates for metastasis founder cells (MFC) in lymph nodes. We isolated MCSP+ DCC from various stages of metastatic colony-formation, performed scRNA-seq and unravelled their phenotypic progression. Further we performed bulk sequencing on patient-derived DCC models (MelDCC) and showed that they exhibit an immunosuppressive activity on CD8 T cells.","abstract":"To dissect the sequence of genotypic and phenotypic progression during early metastatic colonization, we searched for the earliest detectable disseminated cancer cells (DCC) and identified MCSP+ melanoma cells as strong candidates for metastasis founder cells (MFC) in lymph nodes. We isolated MCSP+ DCC from various stages of metastatic colony-formation, performed scRNA-seq and unravelled their phenotypic progression. Further we performed bulk sequencing on patient-derived DCC models (MelDCC) and showed that they exhibit an immunosuppressive activity on CD8 T cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-19T13:23:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006703","title":"High-resolution testing of ctDNA dynamics predicts survival in metastatic NSCLC","description":"One of the great challenges of therapeutic oncology is determining who might achieve survival benefit from a particular therapy. Circulating tumor DNA (ctDNA) provides real-time assessments of patient prognosis and response to treatment using a simple blood draw. While ctDNA positivity is established as a poor prognostic factor, studies on longitudinal ctDNA dynamics have been small and non-randomized, with ctDNA assessments done at disparate time points. To address this, we performed high-sensitivity longitudinal ctDNA testing in 466 patients across 5 time points (1,954 samples total) in a randomized phase III study comparing different chemotherapy-immunotherapy combinations.  We leverage machine learning to jointly model multiple ctDNA metrics to predict overall survival in a training/testing framework. _   . Treatment initiation correlated with reductions in ctDNA levels, and training of our machine learning model suggests that assessment of ctDNA dynamics at C3D1 (cycle 3 day 1) of chemo-IO treatment may be optimal to predict OS. The model performs well in the hold-back test data, enabling stratification of patients with Stable Disease (SD) into high-risk vs low-intermediate-risk (HR = 3.2 [2.0-5.3], p &lt;0.001; median 7.1 versus 22.3 months respectively); similarly, the model stratifies patients with a Partial Response (PR) (HR =3.3 [1.7-6.4], p &lt;0.001; median 8.8 versus 28.6 months). Importantly, the model validates well in an external cohort of patients in a different treatment setting and assayed with a different ctDNA technology, in which model predictions similarly identified high-risk patients (OS HR=3.73 [1.83-7.60], logrank p=0.00012). Simulations of clinical trial scenarios employing our ctDNA model further suggest that early ctDNA testing outperforms early radiographic imaging for predicting trial outcomes (increasing the rate of ‘True Go’ decisions by 5.2 - 22.8% depending on the drug combination). Overall, we show that measuring ctDNA dynamics during the course of therapy dramatically improves patient risk stratification, and may provide a means to differentiate between competing therapies at an early time point during clinical trials.","abstract":"One of the great challenges of therapeutic oncology is determining who might achieve survival benefit from a particular therapy. Circulating tumor DNA (ctDNA) provides real-time assessments of patient prognosis and response to treatment using a simple blood draw. While ctDNA positivity is established as a poor prognostic factor, studies on longitudinal ctDNA dynamics have been small and non-randomized, with ctDNA assessments done at disparate time points. To address this, we performed high-sensitivity longitudinal ctDNA testing in 466 patients across 5 time points (1,954 samples total) in a randomized phase III study comparing different chemotherapy-immunotherapy combinations.  We leverage machine learning to jointly model multiple ctDNA metrics to predict overall survival in a training/testing framework. _   . Treatment initiation correlated with reductions in ctDNA levels, and training of our machine learning model suggests that assessment of ctDNA dynamics at C3D1 (cycle 3 day 1) of chemo-IO treatment may be optimal to predict OS. The model performs well in the hold-back test data, enabling stratification of patients with Stable Disease (SD) into high-risk vs low-intermediate-risk (HR = 3.2 [2.0-5.3], p &lt;0.001; median 7.1 versus 22.3 months respectively); similarly, the model stratifies patients with a Partial Response (PR) (HR =3.3 [1.7-6.4], p &lt;0.001; median 8.8 versus 28.6 months). Importantly, the model validates well in an external cohort of patients in a different treatment setting and assayed with a different ctDNA technology, in which model predictions similarly identified high-risk patients (OS HR=3.73 [1.83-7.60], logrank p=0.00012). Simulations of clinical trial scenarios employing our ctDNA model further suggest that early ctDNA testing outperforms early radiographic imaging for predicting trial outcomes (increasing the rate of ‘True Go’ decisions by 5.2 - 22.8% depending on the drug combination). Overall, we show that measuring ctDNA dynamics during the course of therapy dramatically improves patient risk stratification, and may provide a means to differentiate between competing therapies at an early time point during clinical trials.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-20T01:09:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006704","title":"Whole blood transcriptomic analysis of ANCA-associated vasculitis","description":"Whole blood mRNA sequencing from 30 patients with AAV (granulomatosis with polyangiitis/GPA, n=22) and microscopic polyangiitis (MPA, n=8) combined with functional enrichment and network analysis for aberrant pathways. Key genes and pathways were validated in an independent cohort of 18 AAV patients. Co-expression network and hierarchical clustering analysis, identified molecular endotypes. Multi-level transcriptional overlap analysis to SLE was based on our published data from 142 patients.","abstract":"Whole blood mRNA sequencing from 30 patients with AAV (granulomatosis with polyangiitis/GPA, n=22) and microscopic polyangiitis (MPA, n=8) combined with functional enrichment and network analysis for aberrant pathways. Key genes and pathways were validated in an independent cohort of 18 AAV patients. Co-expression network and hierarchical clustering analysis, identified molecular endotypes. Multi-level transcriptional overlap analysis to SLE was based on our published data from 142 patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-20T11:14:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006705","title":"Germline sequencing","description":"Detection of SNVs/ indels in the germline of pediatric cancer patients with a focus on CHEK2 germline variants","abstract":"Detection of SNVs/ indels in the germline of pediatric cancer patients with a focus on CHEK2 germline variants","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-20T14:07:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006706","title":"Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification (H021)","description":"Systemic pan-tumor analyses may reveal the significance of common features implicated in cancer immunogenicity and patient survival. Here, we provide a comprehensive multi-omics data set for 32 patients across 25 tumor types for proteogenomic-based discovery of neoantigens. By using an optimized computational approach, we discover a large number of tumor-specific and tumor-associated antigens. To create a pipeline for the identification of neoantigens in our cohort, we combine DNA and RNA sequencing with MS-based immunopeptidomics of tumor specimens, followed by the assessment of their immunogenicity and an in-depth validation process. We detect a broad variety of non-canonical HLA-binding peptides in the majority of patients demonstrating partially immunogenicity. Our validation process allows for the selection of 32 potential neoantigen candidates. The majority of neoantigen candidates originates from variants identified in the RNA data set, illustrating the relevance of RNA as a still understudied source of cancer antigens. This study underlines the importance of RNA-centered variant detection for the identification of shared biomarkers and potentially relevant neoantigen candidates.","abstract":"Systemic pan-tumor analyses may reveal the significance of common features implicated in cancer immunogenicity and patient survival. Here, we provide a comprehensive multi-omics data set for 32 patients across 25 tumor types for proteogenomic-based discovery of neoantigens. By using an optimized computational approach, we discover a large number of tumor-specific and tumor-associated antigens. To create a pipeline for the identification of neoantigens in our cohort, we combine DNA and RNA sequencing with MS-based immunopeptidomics of tumor specimens, followed by the assessment of their immunogenicity and an in-depth validation process. We detect a broad variety of non-canonical HLA-binding peptides in the majority of patients demonstrating partially immunogenicity. Our validation process allows for the selection of 32 potential neoantigen candidates. The majority of neoantigen candidates originates from variants identified in the RNA data set, illustrating the relevance of RNA as a still understudied source of cancer antigens. This study underlines the importance of RNA-centered variant detection for the identification of shared biomarkers and potentially relevant neoantigen candidates.","study_type":"Other","pubmed_ids":[37532709],"external_links":null,"is_released":true,"released_date":"2022-10-21T07:31:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006707","title":"The University of Hong Kong Colon Cancer GCV Study","description":"Background: Ganciclovir (GCV) is widely used in solid organ and hematopoietic stem cell transplant patients for prophylaxis and treatment of cytomegalovirus. It has long been considered a mutagen and carcinogen. However, the contribution of GCV to cancer incidence and other factors that influence its mutagenicity remains unknown.\nMethods: This retrospective cohort study analysed genomics data for 121,771 patients who had undergone targeted sequencing compiled by the Genomics Evidence Neoplasia Information Exchange (GENIE) or Foundation Medicine (FM). A statistical approach was developed to identify patients with GCV-associated mutational signature (GCVsig) from targeted sequenced data of tumour samples. Cell line exposure models were further used to quantify mutation burden and DNA damage caused by GCV and other antiviral and immunosuppressive drugs.\nResults: Mutational profiles from 22 of 121,771 patient samples in the GENIE and FM cohorts showed evidence of GCVsig. A diverse range of cancers was represented. All patients with detailed clinical history available had previously undergone solid organ transplantation and received GCV and mycophenolate treatment. RAS hotspot mutations associated with GCVsig¬¬ were present in 9 of the 22 samples, with all samples harbouring multiple GCV-associated protein-altering mutations in cancer driver genes. In vitro testing in cell lines showed that elevated DNA damage response and GCV¬sig are uniquely associated with GCV but not acyclovir, a structurally similar antiviral. Combination treatment of GCV with the immunosuppressant, mycophenolate mofetil (MMF), increased the misincorporation of GCV in genomic DNA and mutations attributed to GCVsig in cell lines and organoids.\nConclusions: In summary, GCV can cause a diverse range of cancers. Its mutagenicity may be potentiated by other therapies, such as mycophenolate, commonly co-prescribed with GCV for post-transplant patients. Further investigation of the optimal use of these drugs could help reduce GCV-associated mutagenesis in post-transplant patients.","abstract":"Background: Ganciclovir (GCV) is widely used in solid organ and hematopoietic stem cell transplant patients for prophylaxis and treatment of cytomegalovirus. It has long been considered a mutagen and carcinogen. However, the contribution of GCV to cancer incidence and other factors that influence its mutagenicity remains unknown.\nMethods: This retrospective cohort study analysed genomics data for 121,771 patients who had undergone targeted sequencing compiled by the Genomics Evidence Neoplasia Information Exchange (GENIE) or Foundation Medicine (FM). A statistical approach was developed to identify patients with GCV-associated mutational signature (GCVsig) from targeted sequenced data of tumour samples. Cell line exposure models were further used to quantify mutation burden and DNA damage caused by GCV and other antiviral and immunosuppressive drugs.\nResults: Mutational profiles from 22 of 121,771 patient samples in the GENIE and FM cohorts showed evidence of GCVsig. A diverse range of cancers was represented. All patients with detailed clinical history available had previously undergone solid organ transplantation and received GCV and mycophenolate treatment. RAS hotspot mutations associated with GCVsig¬¬ were present in 9 of the 22 samples, with all samples harbouring multiple GCV-associated protein-altering mutations in cancer driver genes. In vitro testing in cell lines showed that elevated DNA damage response and GCV¬sig are uniquely associated with GCV but not acyclovir, a structurally similar antiviral. Combination treatment of GCV with the immunosuppressant, mycophenolate mofetil (MMF), increased the misincorporation of GCV in genomic DNA and mutations attributed to GCVsig in cell lines and organoids.\nConclusions: In summary, GCV can cause a diverse range of cancers. Its mutagenicity may be potentiated by other therapies, such as mycophenolate, commonly co-prescribed with GCV for post-transplant patients. Further investigation of the optimal use of these drugs could help reduce GCV-associated mutagenesis in post-transplant patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-21T09:52:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006708","title":"Chemotherapy_effect_on_Parental_germline_WGS","description":"This work aims to investigate the effect of chemotherapy used in cancer treatment on the mutational load and clonal dynamics of pathogenic mutations in parental germline. WGS of blood samples / buccal swabs from families with either parent undergone chemotherapy will be integrated to study the mutations caused by different chemotherapy drugs and assess the transmitibility of these mutations.","abstract":"From recent studies there is evidence of mutations caused due to chemotherapy in the parents to be transmitted to offsprings leading to hypermutator phenotypes. This study aims to investigate the mutagenesis caused by various chemotherapy drugs within the parental germ cells and the likelihood of these mutations conferring some selective advantage and generate smaller clonal expansions and transmit to the next generations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006709","title":"HCA_Blood_Skin_Disease_Atopic_dermatitis___RNA___","description":"Multiomics of skin samples from eczema patients, pre and post dupilumab treatment","abstract":"The aim of this project is to use multi-omics approaches to comprehensively define the in situ transcriptome profile and molecular pathways present in atopic dermatitis and psoriasis skin and integrate these findings with existing suspension single cell datasets (e.g. Reynolds et al., Science 2021). We have collected longitudinal atopic dermatitis and psoriasis skin biopsies and matched blood samples pre- and post-treatment. These samples will be processed and analysed using established multi-omics approaches at the Wellcome Sanger Institute e.g. transcriptomic data will be generated from skin samples using the Visium Spatial Gene Expression protocol, followed by computational integration of single cell and spatial datasets in order to determine the relative abundance and position of cell types and states in distinct spatial locations within atopic dermatitis/psoriasis skin, including during treatment. Some samples (e.g. skin biopsies) will be initially partially processed at Newcastle University prior to transfer to Wellcome Sanger Institute for further processing and analysis. The project will provide the microanatomical definition of dynamic pathological cellular and molecular interactions underpinning perturbations in inflammatory skin disease to help derive new potential therapeutic targets.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006710","title":"Genomic profiling of subcutaneous patient derived xenograft models of solid childhood cancer","description":null,"abstract":"We established 70 subcutaneous PDX models from 16 different pediatric solid tumor subtypes and applied whole-exome sequencing (WES), whole-genome sequencing (WGS) and RNA sequencing (RNA-seq) to both PDX, matched patient tumor (PT) and germline samples. PDXs can generally recapitulate the genomic and transcriptomic features of their matched PT. However, we found a high somatic mutation discrepancy between PDXs and paired PTs in some cases and showed evidence of clonal selection.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-21T21:11:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006711","title":"Hexanucleotide repeat expansions in C9orf72 alter microglial responses and prevent a coordinated glial reaction in ALS","description":"Neuroinflammation is an important hallmark in amyotrophic lateral sclerosis (ALS). Experimental evidence has highlighted a role of microglia in the modulation of motor neuron degeneration. However, the exact contribution of microglia to both sporadic and genetic forms of ALS is still unclear. We generated single nuclei profiles of spinal cord and motor cortex from sporadic and C9orf72 ALS patients, as well as controls. We particularly focused on the transcriptomic responses of both microglia and astrocytes. We confirmed that C9orf72 is highly expressed in microglia and shows a diminished expression in carriers of the hexanucleotide repeat expansion (HRE). This resulted in an impaired response to disease, with specific deficits in phagocytic and lysosomal transcriptional pathways. Astrocytes also displayed a dysregulated response in C9orf72 ALS patients, remaining in a homeostatic state. This suggests that C9orf72 HRE alters a coordinated glial response, which ultimately would increase the risk for developing ALS. Our results indicate that C9orf72 HRE results in a selective microglial loss-of-function, likely impairing microglial-astrocyte communication and preventing a global glial response. This is relevant as it indicates that sporadic and familial forms of ALS may present a different cellular substrate, which is of great importance for patient stratification and treatment.","abstract":"Neuroinflammation is an important hallmark in amyotrophic lateral sclerosis (ALS). Experimental evidence has highlighted a role of microglia in the modulation of motor neuron degeneration. However, the exact contribution of microglia to both sporadic and genetic forms of ALS is still unclear. We generated single nuclei profiles of spinal cord and motor cortex from sporadic and C9orf72 ALS patients, as well as controls. We particularly focused on the transcriptomic responses of both microglia and astrocytes. We confirmed that C9orf72 is highly expressed in microglia and shows a diminished expression in carriers of the hexanucleotide repeat expansion (HRE). This resulted in an impaired response to disease, with specific deficits in phagocytic and lysosomal transcriptional pathways. Astrocytes also displayed a dysregulated response in C9orf72 ALS patients, remaining in a homeostatic state. This suggests that C9orf72 HRE alters a coordinated glial response, which ultimately would increase the risk for developing ALS. Our results indicate that C9orf72 HRE results in a selective microglial loss-of-function, likely impairing microglial-astrocyte communication and preventing a global glial response. This is relevant as it indicates that sporadic and familial forms of ALS may present a different cellular substrate, which is of great importance for patient stratification and treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-22T11:24:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006712","title":"DNA methylation-based classification of sinonasal tumors [Proteomics data]","description":"The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent previously misclassified adenoid cystic carcinomas. The repository includes the raw mass spectrometry-based proteomics data","abstract":"The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent previously misclassified adenoid cystic carcinomas. The repository includes the raw mass spectrometry-based proteomics data","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-23T12:42:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006713","title":"DNA methylation-based classification of sinonasal tumors [DNA sequencing]","description":"The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent previously misclassified adenoid cystic carcinomas.  This repository includes the results from DNA sequencing and mass spectrometry-based proteomics.","abstract":"The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent previously misclassified adenoid cystic carcinomas.  This repository includes the results from DNA sequencing and mass spectrometry-based proteomics.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-23T13:38:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006714","title":"A total of 40 Multiple Myeloma (MM) patients at clinical relapse who progressed during Proteasome Inhibitors (PIs) or Immunomodulating Drugs (IMiDs)-based therapies and who are assigned to antiCD38-based salvage treatments, will be enrolled. We will collect bone marrow (BM) and peripheral blood (PB) samples from patients at specific timepoints:      baseline (BM, PB and buccal swab)     every 3 month (PB)     achievement of response (≥ Very Good Partial Response (VGPR)) (BM and PB)     relapse or refractory status to antiCD38-based treatments (BM and PB) Samples will be processed and stored in the 'Hematological Laboratory' located in the University of Turin (Italy) for various proposed analyses: at specific time-points CD138+ (Plasma Cells-PCs) awill be immunomagnetically enriched from the BM mononuclear cells and frozen as viable cells in dimethyl sulfoxide (DMSO); PB mononuclear cells (PBMCs) will be isolated from whole blood by density-gradient centrifugation, and frozen as above; plasma fraction from PB and BM will be obtained by centrifugation and stored frozen; Neutrophils will be obtained at the time of enrollment as a source of control germline DNA and stored frozen.","description":"Aim 1: Evaluation of cell-intrinsic mechanisms on BM.\n\n    Whole Genome Sequencing (WGS) and Whole Exome Sequencing (WES) will be performed on marker CD138+ purified cells to evaluate their genomic profile, and on neutrophils to restrict the analysis to variants or structural abnormalities that have a clear somatic status, and are therefore specific to the tumor cells. In details:\n\n    Flow cytometry analysis will be performed on BM samples to examine potential determinants of immunotherapy sensitivity/resistance and the expression of specific targets including marker Cluster of Differentiation 38 (CD38) prior to treatment, at response and at relapse. We will evaluate MM percent positive cells and Mean Fluorescence Intensity (MFI) in order to monitor the antigen expression during the evolution of the disease. Receptor density will also be performed. Moreover the European cytoflow consortium of International Myeloma Foundation (EuroFlow-IMF) MM minimal residual disease (MRD) panel will be applied to monitor MRD in particular by using a multiepitope (ME) antiCD38 to detect possible determinants of resistance. Moreover this panel will allow us to monitor the phenotype evolution of the clonal population, looking in particular at the shift towards more immature cells, which has been suggested as a mechanism of resistance to bortezomib.\n\nAim 2: Evaluation of cell-extrinsic mechanism on BM and PB.\n\n    Flow Cytometry analysis of lymphocyte subpopulations will be performed in the same BM and PB to evaluate T-cells population (marker CD38+, marker Cluster of Differentiation 4 (CD4+), marker Cluster of Differentiation 8 (CD8+), Tregs cells) and other regulatory and suppressive immune populations like Myeloid-Derived Suppressor Cells (MDSCs). T cells will be measured at baseline, response and at relapse, and they could help in evaluating the interaction between B and T cell compartments in patients receiving immunotherapies. Moreover, evaluation of some immune checkpoints on T cells at baseline and post-treatment will be performed.\nT-lymphocytic subpopulations in responsive and non-responsive MM to identify potential suppressive signatures in the latter group. \n  BM biopsy: bone biopsies from MM patients at baseline and after Monoclonal Antibody Therapy (mAbs therapy) will be evaluated \n\nAim 3: After comprehensively characterizing the genomic and immunophenotypic features of CD138+ cells, and having a clear picture of the effector/suppressive immune population in MM, we will then correlate these features with clinical data. In detail, we will create a database including the following columns:\n\n    Baseline clinical characteristics\n    Prognostic factors: International Staging System (ISS), Revised International Staging System (R-ISS), Lactate Dehydrogenase (LDH), cytogenetic analysis by Fluorescence In Situ Hybridization test (FISH)\n    Prior therapies and relevant clinical results\n    Best response: responses will be defined according to the International Uniform Response Criteria. Responders are defined as subjects with at least a VGPR.\n    Duration of Response (DOR), Progression Free Survival (PFS), Overall survival (OS) and Time to Progression (TTP) data In this aim, we will look for correlation between biological features and disease response or lack thereof, to understand which cell-intrinsic and cell-extrinsic features are better predictors of response. Because of the time needed before disease response can be assessed, this analysis will be performed after at least 1 year of treatment or at earlier progression. In a first analysis, biological features will be associated with best response to treatment, PFS and other baseline clinical, prognostic and treatment variables using linear models. Subsequently, starting from year 3, when enough follow-up will allow a meaningful analysis of PFS and OS, Kaplan-Meier and Coxregression models will be fitted to identify possible independent prognostic factors.\n\nAlthough the relatively small size of the cohort will limit statistical power and the possibility to perform subgroup analysis, this attempt to identify biomarkers could improve the clinical management of the patient, by prioritizing the vast array of salvage treatments in MM and thus decreasing costs.","abstract":"Aim 1: Evaluation of cell-intrinsic mechanisms on BM.\n\n    Whole Genome Sequencing (WGS) and Whole Exome Sequencing (WES) will be performed on marker CD138+ purified cells to evaluate their genomic profile, and on neutrophils to restrict the analysis to variants or structural abnormalities that have a clear somatic status, and are therefore specific to the tumor cells. In details:\n\n    Flow cytometry analysis will be performed on BM samples to examine potential determinants of immunotherapy sensitivity/resistance and the expression of specific targets including marker Cluster of Differentiation 38 (CD38) prior to treatment, at response and at relapse. We will evaluate MM percent positive cells and Mean Fluorescence Intensity (MFI) in order to monitor the antigen expression during the evolution of the disease. Receptor density will also be performed. Moreover the European cytoflow consortium of International Myeloma Foundation (EuroFlow-IMF) MM minimal residual disease (MRD) panel will be applied to monitor MRD in particular by using a multiepitope (ME) antiCD38 to detect possible determinants of resistance. Moreover this panel will allow us to monitor the phenotype evolution of the clonal population, looking in particular at the shift towards more immature cells, which has been suggested as a mechanism of resistance to bortezomib.\n\nAim 2: Evaluation of cell-extrinsic mechanism on BM and PB.\n\n    Flow Cytometry analysis of lymphocyte subpopulations will be performed in the same BM and PB to evaluate T-cells population (marker CD38+, marker Cluster of Differentiation 4 (CD4+), marker Cluster of Differentiation 8 (CD8+), Tregs cells) and other regulatory and suppressive immune populations like Myeloid-Derived Suppressor Cells (MDSCs). T cells will be measured at baseline, response and at relapse, and they could help in evaluating the interaction between B and T cell compartments in patients receiving immunotherapies. Moreover, evaluation of some immune checkpoints on T cells at baseline and post-treatment will be performed.\nT-lymphocytic subpopulations in responsive and non-responsive MM to identify potential suppressive signatures in the latter group. \n  BM biopsy: bone biopsies from MM patients at baseline and after Monoclonal Antibody Therapy (mAbs therapy) will be evaluated \n\nAim 3: After comprehensively characterizing the genomic and immunophenotypic features of CD138+ cells, and having a clear picture of the effector/suppressive immune population in MM, we will then correlate these features with clinical data. In detail, we will create a database including the following columns:\n\n    Baseline clinical characteristics\n    Prognostic factors: International Staging System (ISS), Revised International Staging System (R-ISS), Lactate Dehydrogenase (LDH), cytogenetic analysis by Fluorescence In Situ Hybridization test (FISH)\n    Prior therapies and relevant clinical results\n    Best response: responses will be defined according to the International Uniform Response Criteria. Responders are defined as subjects with at least a VGPR.\n    Duration of Response (DOR), Progression Free Survival (PFS), Overall survival (OS) and Time to Progression (TTP) data In this aim, we will look for correlation between biological features and disease response or lack thereof, to understand which cell-intrinsic and cell-extrinsic features are better predictors of response. Because of the time needed before disease response can be assessed, this analysis will be performed after at least 1 year of treatment or at earlier progression. In a first analysis, biological features will be associated with best response to treatment, PFS and other baseline clinical, prognostic and treatment variables using linear models. Subsequently, starting from year 3, when enough follow-up will allow a meaningful analysis of PFS and OS, Kaplan-Meier and Coxregression models will be fitted to identify possible independent prognostic factors.\n\nAlthough the relatively small size of the cohort will limit statistical power and the possibility to perform subgroup analysis, this attempt to identify biomarkers could improve the clinical management of the patient, by prioritizing the vast array of salvage treatments in MM and thus decreasing costs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006715","title":"Multifocal cohort analysis unveils cell types associated with regional lymph node seeding in prostate cancer","description":"The aim of this project was to assess the effect of intratumor heterogeneity on pathological and molecular markers in locally advanced prostate cancer. We demonstrate how primary lesions with a higher metastatic potential more closely resemble the state in the metastatic lymph nodes, for some biological signatures. Finally, we developed a statistical procedure to identify the most likely seeding lesion and introduced a statistical testing procedure to leverage the intratumor heterogeneity to identify signatures that characterize the seeding lesion.","abstract":"The aim of this project was to assess the effect of intratumor heterogeneity on pathological and molecular markers in locally advanced prostate cancer. We demonstrate how primary lesions with a higher metastatic potential more closely resemble the state in the metastatic lymph nodes, for some biological signatures. Finally, we developed a statistical procedure to identify the most likely seeding lesion and introduced a statistical testing procedure to leverage the intratumor heterogeneity to identify signatures that characterize the seeding lesion.","study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-24T12:56:13.543278+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006716","title":"A single-cell transcriptional gradient in human cutaneous memory T cells restricts Th17/Tc17 identity","description":"We identified a gradated transcriptional program of coordinately regulated inflammation-suppressive genes in psoriatic resident memory T cells. This dataset includes bulk RNA-seq for CRISPR-based deactivation of two core components of this inflammation-suppressive program, ZFP36L2 and ZFP36, in human PBMCs. It also includes scRNA-seq of cutaneous immune cells from psoriasis patients before and during therapeutic IL-23 blockade.","abstract":"We identified a gradated transcriptional program of coordinately regulated inflammation-suppressive genes in psoriatic resident memory T cells. This dataset includes bulk RNA-seq for CRISPR-based deactivation of two core components of this inflammation-suppressive program, ZFP36L2 and ZFP36, in human PBMCs. It also includes scRNA-seq of cutaneous immune cells from psoriasis patients before and during therapeutic IL-23 blockade.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-26T23:48:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006717","title":"Pilot_For_Primary_Immunodeficiency_Cells_Wc10426_Single_Cell_Profiling","description":"Inborn errors of immunity (IEI) are a group of rare, inherited disorders in which mutations in immune genes lead to severe impairment of the immune system. As a proof-of-concept, we will focus on genes (CTLA4, STAT3, FOXP3, LRBA) that impair the function of Tregs and result in primary immunodeficiency. Tregs play a critical role in suppressing the immune response and depletion of Tregs results in inability to downregulate inflammation. The selected genes all affect different mechanisms of Treg functions (e.g. receptors, ligands, transcription factors), therefore, whole transcriptome profiling might reveal shared Treg signatures as well as point towards gene-specific footprints.","abstract":"Inborn errors of immunity (IEI) are a group of rare, inherited disorders in which mutations in immune genes lead to severe impairment of the immune system. In this study, we  analyzed cells from patients with mutations in genes involved in Treg function (CTLA4, STAT3, FOXP3, LRBA) and age-matched control individuals. Tregs play a critical role in suppressing the immune response and depletion of Tregs results in inability to downregulate inflammation. The selected genes all affect different mechanisms of Treg functions (e.g. receptors, ligands, transcription factors), therefore, whole transcriptome profiling might reveal shared Treg signatures as well as point towards gene-specific footprints.\nWe analysed gene expression, expression of a set of surface proteins and TCR/BCR repertoire in selected subsets of PBMCs at single cell level with Chromium 5’ 10X\ngenomics. Additionaly, for 16 individuals chosen across disease groups, we used BD Rhapsody to  analyse  surface protein markers and TCRs and gene expression with more sensitivity for a panel of ~400 T-cell specific genes.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006718","title":"Test Study for EGA using data from 1000 Genomes Project - Big CRAM, BAM, VCF and BCF files used for testing","description":"This is a test study for EGA using data from 1000 Genomes Project, specifically created to add more diversity to the existing dataset EGAD00001003338. This Test Study should NOT be confused with the real study of 1000 Genomes Project - Phase 3. Specifically, this study encompasses 4 CRAM, 4 BAM, 2 VCF and 2 BCF files, of different sizes (all above 1 GB), used for testing downloads and monitoring services. It also contains their respective indexes: crai for crams, bai for bams, tbi for vcfs and csi for bcfs.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2017-10-11T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006719","title":"Whole genome sequencing of AVM endothelial and non-endothelial cell fractions","description":"We previously identified somatic activating KRAS mutations in a majority of human arteriovenous malformations (AVMs), using whole exome sequencing, which were enhanced in AVM endothelial cell fractions. We have now performed whole genome sequencing on AVM endothelial and non-endothelial cell fractions, as well as paired blood samples, in order to identify further somatic mutations.","abstract":"We previously identified somatic activating KRAS mutations in a majority of human arteriovenous malformations (AVMs), using whole exome sequencing, which were enhanced in AVM endothelial cell fractions. We have now performed whole genome sequencing on AVM endothelial and non-endothelial cell fractions, as well as paired blood samples, in order to identify further somatic mutations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-28T19:55:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006720","title":"Sputum fungal microbiota in an overall healthy population in Guangdong province, China","description":"This repository contains raw sequencing data for sputum fungal microbiota in an overall healthy population in Guangdong province, China. The aim of the study is to provide a comprehensive insight on the multi-kingdom airway microbiome, how it may underlie the interplay between exposure and healthy outcomes, and whether it can be employed to inform airway health and diseases.","abstract":"This repository contains raw sequencing data for sputum fungal microbiota in an overall healthy population in Guangdong province, China. The aim of the study is to provide a comprehensive insight on the multi-kingdom airway microbiome, how it may underlie the interplay between exposure and healthy outcomes, and whether it can be employed to inform airway health and diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-29T11:05:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006721","title":"Sputum bacterial microbiota in an overall healthy population in Guangdong province, China","description":"This repository contains raw sequencing data for sputum fungal microbiota in an overall healthy population in Guangdong province, China. The aim of the study is to provide a comprehensive insight on the multi-kingdom airway microbiome, how it may underlie the interplay between exposure and healthy outcomes, and whether it can be employed to inform airway health and diseases.","abstract":"This repository contains raw sequencing data for sputum fungal microbiota in an overall healthy population in Guangdong province, China. The aim of the study is to provide a comprehensive insight on the multi-kingdom airway microbiome, how it may underlie the interplay between exposure and healthy outcomes, and whether it can be employed to inform airway health and diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-29T11:06:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001006722","title":"Multi-omics analysis of an individual with multiple pancreatic neuroendocrine tumours (panNETs)","description":null,"abstract":"Whole exome and RNASeq raw sequencing data for an individual with multiple pancreatic neuroendocrine tumours (panNETs). Age at diagnosis was 51. Tumour tissue and PBMCs were used for sequencing.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-31T12:17:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006723","title":"Deconvolution of bulk RNA-Seq using single cell RNA-Seq","description":"In this study single cell RNA-Seq data was used to train a deconvolution algorithm. The algorithm was validated on paired bulk RNA-Seq profiles.","abstract":"In this study single cell RNA-Seq data was used to train a deconvolution algorithm. The algorithm was validated on paired bulk RNA-Seq profiles.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-10-31T14:30:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006724","title":"Comprehensive Whole-Genome Sequence Annotation to Resolve the Genetic Architecture of Cerebral Palsy","description":null,"abstract":"Cerebral palsy (CP) is a permanent, non-progressive brain injury leading to movement and posture disorders. It can involve comorbidities, including other neurodevelopmental disorders (NDD). Genomic studies, focused mainly on the role of copy number variations (CNVs) identified using whole genome microarrays, and rare single nucleotide variants (SNVs) and insertions/deletions (indels) from exome sequencing, have shown that genomic changes have increasingly been found to play a role in etiology of CP and other NDDs. We applied Whole Genome Sequencing (WGS) to uncover a more complete landscape of genetic variations in both nuclear and mitochondrial DNA (CNVs, structural variations (SVs), SNVs, indels, tandem repeat (TR) variations, and mitochondrial DNA (mtDNA) variations) on a representative sample of individuals with CP recruited from CP-NET (Ontario) and the Canadian CP Registry. The cohort included 308 complete trio and four quartet families.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-01T14:17:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006725","title":"Whole genome sequencing dataset of 200 trio families from the CHILD cohort study.","description":null,"abstract":"This whole genome sequence dataset of 200 trio families (600 samples) is a population control cohort from CHILD cohort study. CHILD is the largest multidisciplinary, longitudinal, population-based birth cohort study in Canada and is designed to be one of the most informative studies of its kind in the world. The samples were sequenced on the HiSeqX platform. The dataset will facilitate discovery of medically relevant variants for a wider variety of studies in human disease and health by helping to further catalogue variation in control populations, and also to establish baseline tempo and modes of mutation. No similar dataset yet exists and research studies are being restricted because of this.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-01T15:42:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006726","title":"DERMATLAS__Pilar_cyst_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are pilar cysts.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are pilar cysts.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006727","title":"Bulk RNAseq of mCRC organoids","description":"Transcriptomic profiles of 6 mCRC organoids","abstract":"Transcriptomic profiles of 6 mCRC organoids","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-02T12:54:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006728","title":"Single cell RNA-sequencing of tissues from NSCLC patients treated with chemoimmunotherapy","description":null,"abstract":"The goal of this study is to characterize immune cell populations by single cell RNA-sequencing (scRNA-seq) in tumor and uninvolved normal tissues from non-small cell lung cancer (NSCLC) patients with resectable non-small cell lung cancer and who received neoadjuvant chemoimmunotherapy. scRNA-seq was performed on seven pairs of tumor and normal tissues as well as one lymph node (LN) sample.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-02T14:23:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006729","title":"Targeted sequencing of brain AVM tissues","description":"We previously identified somatic activating KRAS mutations in a majority of human arteriovenous malformations (AVMs), using whole exome sequencing. We have now performed targeted sequencing on AVMS, investigating genes in the RAS-MAPK pathway, angiogenesis and brain vascular disorders among others.","abstract":"We previously identified somatic activating KRAS mutations in a majority of human arteriovenous malformations (AVMs), using whole exome sequencing. We have now performed targeted sequencing on AVMS, investigating genes in the RAS-MAPK pathway, angiogenesis and brain vascular disorders among others.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-02T17:25:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006730","title":"Measurement of SARS-CoV-2 variants fraction in infected alveolar cells","description":"With the continuous emergence of highly transmissible SARS-CoV-2 variants, the comparison of their infectivity has become a critical issue for public health. However, a direct assessment of the viral characteristic has been challenging due to the lack of appropriate experimental models and efficient methods. Here, we conducted full-length transcriptome sequencing of single human alveolar cells infected by multiple SARS-CoV-2 variants, including GR (B.1.1.119), Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (BA.1). Using unique mutations of each VOC, we calculated the fraction of VOCs in infected cells.","abstract":"With the continuous emergence of highly transmissible SARS-CoV-2 variants, the comparison of their infectivity has become a critical issue for public health. However, a direct assessment of the viral characteristic has been challenging due to the lack of appropriate experimental models and efficient methods. Here, we conducted full-length transcriptome sequencing of single human alveolar cells infected by multiple SARS-CoV-2 variants, including GR (B.1.1.119), Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (BA.1). Using unique mutations of each VOC, we calculated the fraction of VOCs in infected cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-03T02:31:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006731","title":"WGS of CD138+ samples collected from MM patients","description":"Deep WGS performed on samples collected from MM patients","abstract":"Deep WGS performed on samples collected from MM patients","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-03T04:40:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006732","title":"GENOMIC MUTATION LANDSCAPE OF SKIN CANCERS FROM DNA REPAIR-DEFICIENT XERODERMA PIGMENTOSUM PATIENTS","description":"Xeroderma pigmentosum (XP) is a genetic disorder caused by mutations in genes of the Nucleotide Excision Repair (NER) pathway (groups A-G) or in Translesion Synthesis (TLS) DNA polymerase η (group V). XP is associated with an increased skin cancer risk, reaching, for some groups, several thousand-fold compared to the general population. Here, we analyzed 38 skin cancer genomes from five XP groups. We found that the activity of NER determines heterogeneity of the mutation rates across skin cancer genomes and that transcription-coupled NER extends beyond the gene boundaries reducing the intergenic mutation rate. Mutational profile in XP-V tumors revealed the role of polymerase η in the error-free bypass of (i) rare TpG and TpA DNA lesions, (ii) 3’ nucleotides in pyrimidine dimers, and (iii) TpT photodimers. Our study unravels the genetic basis of skin cancer risk in XP and provides insights into the mechanisms reducing UV-induced mutagenesis in the general population.","abstract":"Xeroderma pigmentosum (XP) is a genetic disorder caused by mutations in genes of the Nucleotide Excision Repair (NER) pathway (groups A-G) or in Translesion Synthesis (TLS) DNA polymerase η (group V). XP is associated with an increased skin cancer risk, reaching, for some groups, several thousand-fold compared to the general population. Here, we analyzed 38 skin cancer genomes from five XP groups. We found that the activity of NER determines heterogeneity of the mutation rates across skin cancer genomes and that transcription-coupled NER extends beyond the gene boundaries reducing the intergenic mutation rate. Mutational profile in XP-V tumors revealed the role of polymerase η in the error-free bypass of (i) rare TpG and TpA DNA lesions, (ii) 3’ nucleotides in pyrimidine dimers, and (iii) TpT photodimers. Our study unravels the genetic basis of skin cancer risk in XP and provides insights into the mechanisms reducing UV-induced mutagenesis in the general population.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-03T06:21:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006733","title":"Non_Hodgkin_lymphoma_project___mutational_burden_of_chemotherapy_in_normal_blood","description":"his study aims to further investigate the mutational burden induced by chemotherapy in the normal stem and progenitor cell of individuals treated for Non -hodgkins lymphoma. Single cell derived progenitor colonies have been grown and DNA extracted. 5-10 colonies from a number of individuals exposed to chemotherapeutic regimens for lymphoma will undergo whole genome sequencing to address the question of the extent of mutational impact of these different regimens.","abstract":"This study aims to further investigate the mutational burden induced by chemotherapy in the normal stem and progenitor cell of individuals treated for Non -hodgkins lymphoma. Single cell derived progenitor colonies have been grown and DNA extracted. 5-10 colonies from a number of individuals exposed to chemotherapeutic regimens for lymphoma will undergo whole genome sequencing to address the question of the extent of mutational impact of these different regimens.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-03T12:15:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006734","title":"Targeted_NanoSeq__Stomach_","description":"Targeted NanoSeq in stomach samples from a number of donors, including donors with and without malignancy. Samples may contain pre-malignant histology A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across a large number of stomach specimens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006735","title":"MLL_leukemia_clonal_origin","description":"In order to study the clonal origin of MLL-rearranged childhood leukemia, we perform whole genome sequencing of single-cell-derived colonies of both normal and leukemic CD34+ cells in multiple patients. The primary question is the timing of: 1) the MLL translocation; 2) the leukemic expansion. To some extent and given certain assumptions this can be answered by sequencing only the leukemic cells and quantifying the number of shared mutations. Sequencing of normal HSPCs will gain additional insights. First, it will allow us to time the leukemic expansion in terms of divergence from the normal phylogenetic tree, providing an estimate less dependent on the number of shared mutations across leukemic cells. Second, it could provide additional timing markers, if used in conjunction with other data sources such as buccal swap DNA sequencing (gastrulation marker) and RNAseq data (in the case of females, X-inactivation timing). Third, comparison with the normal HSPC phylogenetic tree may show that the leukemia develops from an already expanded “normal” clade.","abstract":"In order to study the clonal origin of MLL-rearranged childhood leukemia, we perform whole genome sequencing of single-cell-derived colonies of both normal and leukemic CD34+ cells in multiple patients. The primary question is the timing of: 1) the MLL translocation; 2) the leukemic expansion. Sequencing of leukemic cells and normal HSPCs will allow us to time the leukemic expansion in terms of divergence from the normal phylogenetic tree and trace the fetal origins of MLL-rearranged leukemia.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006736","title":"NIBIT-M4 Clinical Trial samples","description":"Patients (N=14) with unresectable stage III/IV melanoma received escalating doses of guadecitabine 30, 45, or 60 mg/m2/day subcutaneously on days 1 to 5 every 3 weeks, and ipilimumab 3 mg/kg intravenously on day 1 every 3 weeks, starting 1 week after guadecitabine, for four cycles. \nPatient-wise genome-wide DNA methylation, Whole Exome and RNA sequencing were then performed for samples obtained by surgical removal or fine-needle biopsy at baseline (W0), week 4 (W4) and week 12 (W12) after treatment. For Whole Exome Sequencing profiling, normal matched skin tissue was available only for the first eight patients.","abstract":"Patients (N=14) with unresectable stage III/IV melanoma received escalating doses of guadecitabine 30, 45, or 60 mg/m2/day subcutaneously on days 1 to 5 every 3 weeks, and ipilimumab 3 mg/kg intravenously on day 1 every 3 weeks, starting 1 week after guadecitabine, for four cycles. \nPatient-wise genome-wide DNA methylation, Whole Exome and RNA sequencing were then performed for samples obtained by surgical removal or fine-needle biopsy at baseline (W0), week 4 (W4) and week 12 (W12) after treatment. For Whole Exome Sequencing profiling, normal matched skin tissue was available only for the first eight patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-04T14:39:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006737","title":"GOSH_Tumour_Embryology_Paediatric_Behjati_RNA_Managed_Access","description":"The aim of the study is to study thyroid development and function, and how this is altered in Down Syndrome and Thyroid Cancer.","abstract":"The aim of the study is to study thyroid development and function, and how this is altered in Down Syndrome and Thyroid Cancer.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-07T10:57:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006738","title":"HCA_Hormone_glands_Vento_spatial","description":"Study of the cross-talk between the hormone-producing glands from embryos at different ages for both males and females.","abstract":"Hormones are chemical messengers that are important in balancing different processing in adult life. They are secreted from hormone-producing glands to the bloodstream to act on distal organs in the body. Usually, they are present at a low amount and for a given time point. Dysregulation of hormonal levels has a direct impact on our physiological and psychological lifestyle. While the adult endocrine system is heavily studied, the molecular basics and dynamics of the endocrine system at embryonic stages are still understudied. As the interaction between hormones is essential for the proper development of the embryo, the activation time of these organs becomes a critical issue when it is related to their maturation during embryonic life. In this project, I will focus on studying the cross-talk between the hormone-producing glands from embryos at different ages for both males and females. I will generate a single-cell atlas by integrating transcriptome and chromatin accessibility state of the major hormone-producing glands, including the hypothalamus, pituitary, adrenal, pancreas, thyroid, gonads and placenta. Biosynthetic, transport and degradation pathways of various hormones will be constructed from transcriptomic data and crossed between the analysed organs to assess inter-organ interactions. Spatial transcriptomics and proteins imaging with be utilised to validate potential targets at the intact tissue level. Later, samples of glands pathologies will be included to study the systemic influence caused by the imbalanced cellular representation of a given organ. The study outcomes are important and of significant impact in understanding the timing and activity of the different hormones during embryonic life and can serve as a reference for studying the potential effect of hormonal imbalance on embryos during pregnancy.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006739","title":"Neoadjuvant Chemo or Combined Chemo-Radiation Therapy of Pancreatic Ductal Adenocarcinoma Yields Fundamentally Different Proteome Biology of the Residual Tumor Mass","description":"We performed data independent acquisition (DIA)-based proteomics to characterize the proteomes of 67 PDAC resection specimens. Patients received either neoadjuvant chemotherapy or neoadjuvant combined chemo-radiation therapy. We employed DIA, yielding a proteome coverage in excess of 3,500 proteins. The two neoadjuvant therapies yielded highly distinguishable proteome profiles of the residual tumor mass.","abstract":"We performed data independent acquisition (DIA)-based proteomics to characterize the proteomes of 67 PDAC resection specimens. Patients received either neoadjuvant chemotherapy or neoadjuvant combined chemo-radiation therapy. We employed DIA, yielding a proteome coverage in excess of 3,500 proteins. The two neoadjuvant therapies yielded highly distinguishable proteome profiles of the residual tumor mass.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-07T13:56:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006740","title":"Spectrum of SPTCL and HLH with HAVCR2 mutations","description":null,"abstract":"The study aimed to evaluate clinical variations and associated factors among patients with SPTCL and/or HLH with/without germline HAVCR2 mutations. Direct sequencing of HAVCR2Y82C was performed using DNA from patients with SPTCL and/or idiopathic HLH/HLH-like systemic illnesses. Whole exome sequencing was done in some selected cases with HAVCR2Y82C mutation.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006741","title":"Chromatin landscape of medulloblastoma reveals context dependent driver","description":"In this study, we defined subgroup specific chromatin landscape (H3K27ac, H3K27me3, RNA-Seq, 27ac hichip, WGS) of medulloblastoma to identify pathogenic epigenetic alterations that regulate expression of a context dependent driver gene.","abstract":"In this study, we defined subgroup specific chromatin landscape (H3K27ac, H3K27me3, RNA-Seq, 27ac hichip, WGS) of medulloblastoma to identify pathogenic epigenetic alterations that regulate expression of a context dependent driver gene.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-07T19:13:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006742","title":"DERMATLAS: Secretory carcinoma","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are a collection of different types of rare/infrequently-occurring skin tumours (with only a few cases of each).","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are a collection of different types of rare/infrequently-occurring skin tumours (with only a few cases of each).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006743","title":"DERMALTAS: Secretory carcinoma","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are a collection of different types of rare/infrequently-occurring skin tumours (with only a few cases of each).","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are a collection of different types of rare/infrequently-occurring skin tumours (with only a few cases of each).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006744","title":"Structural Expression of BMMF in tissues of colorectal, lung and pancreatic cancer patients","description":"Chronic inflammation, linked to the presence of bovine milk and meat factors (BMMF) and specific subsets of macrophages, results in oxygen radical synthesis and induction of mutations in DNA of actively replicating cells and replicating single stranded DNA (zur Hausen et al., 2017). Cancers arising from this process have been characterized as indirect carcinogenesis by infectious agents (without persistence of genes of the agent in premalignant or cancers cells). Here we investigate structural properties of pleomorphic vesicles, regularly identified by staining peritumour tissues of colorectal, lung and pancreatic cancer for expression of BMMF Rep. The latter represents a subgroup of BMMF1 proteins involved in replication of small single-stranded circular plasmids of BMMF, but most likely also contributing to pleomorphic vesicular structures found in the periphery of colorectal, lung and pancreatic cancers. Structurally dense regions are demonstrated in preselected areas of colorectal cancer, after staining with monoclonal antibodies against BMMF1 Rep. Similar structures were observed in human embryonic cells (HEK293TT) overexpressing Rep. These data suggest that Rep or Rep isoforms contribute to the structural formation of vesicles.","abstract":"Chronic inflammation, linked to the presence of bovine milk and meat factors (BMMF) and specific subsets of macrophages, results in oxygen radical synthesis and induction of mutations in DNA of actively replicating cells and replicating single stranded DNA (zur Hausen et al., 2017). Cancers arising from this process have been characterized as indirect carcinogenesis by infectious agents (without persistence of genes of the agent in premalignant or cancers cells). Here we investigate structural properties of pleomorphic vesicles, regularly identified by staining peritumour tissues of colorectal, lung and pancreatic cancer for expression of BMMF Rep. The latter represents a subgroup of BMMF1 proteins involved in replication of small single-stranded circular plasmids of BMMF, but most likely also contributing to pleomorphic vesicular structures found in the periphery of colorectal, lung and pancreatic cancers. Structurally dense regions are demonstrated in preselected areas of colorectal cancer, after staining with monoclonal antibodies against BMMF1 Rep. Similar structures were observed in human embryonic cells (HEK293TT) overexpressing Rep. These data suggest that Rep or Rep isoforms contribute to the structural formation of vesicles.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-08T15:14:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006745","title":"RNA_sequencing_on_longitudinal_sepsis_samples_from_the_GAinS_study","description":"Sepsis is a heterogeneous clinical syndrome defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The Genomic Advances in Sepsis (GAinS) study has recruited ~2000 adult patients with sepsis due to community acquired pneumonia or faecal peritonitis upon admission to intensive care units across the UK. We have previously used whole blood gene expression data, primarily focusing on the first day in ICU, to explore patient heterogeneity and identify subgroups informative for prognosis and response to treatment. Here, we aim to investigate disease progression and patient variability over time by generating RNA sequencing data on serial samples from the same patients. The dataset will comprise 190 samples taken on the 1st, 3rd, and 5th days of ICU admission.","abstract":"Sepsis is a heterogeneous clinical syndrome defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The Genomic Advances in Sepsis (GAinS) study has recruited ~2000 adult patients with sepsis due to community acquired pneumonia or faecal peritonitis upon admission to intensive care units across the UK. We have previously used whole blood gene expression data, primarily focusing on the first day in ICU, to explore patient heterogeneity and identify subgroups informative for prognosis and response to treatment. Here, we aim to investigate disease progression and patient variability over time by generating RNA sequencing data on serial samples from the same patients. The dataset will comprise 190 samples taken on the 1st, 3rd, and 5th days of ICU admission.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006746","title":"Human primary and metastatic colorectal cancer (CRC) samples","description":null,"abstract":"Bank of human both primary and metastastic colorectal cancer sample RNAseq","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-09T11:14:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006747","title":"Targeted therapy of advanced parathyroid carcinoma guided by genomic and transcriptomic profiling (hipo_021)","description":"Parathyroid carcinoma (PC) is an orphan malignancy with a high risk of recurrence after surgery. Tumor-directed systemic treatments for PC are not established. We used whole-genome and RNA sequencing in four patients with advanced PC to identify molecular alterations that could guide clinical management. In two cases, the genomic and transcriptomic profiles provided targets for experimental therapies that resulted in biochemical response and prolonged disease stabilization: (i) immune checkpoint inhibition with pembrolizumab based on high tumor mutational burden and a single-base substitution signature associated with APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) overactivation; (ii) multi-receptor tyrosine kinase inhibition with lenvatinib due to overexpression of FGFR1 and RET and, later in the course of disease, PARP inhibition with olaparib prompted by signs of defective homologous recombination DNA repair. In addition, our data provided new insights into the molecular landscape of PC with respect to the genome-wide footprints of specific mutational processes and pathogenic germline alterations. These data underscore the potential of comprehensive molecular analyses to improve care for patients with ultra-rare cancers based on insight into disease biology.","abstract":"Parathyroid carcinoma (PC) is an orphan malignancy with a high risk of recurrence after surgery. Tumor-directed systemic treatments for PC are not established. We used whole-genome and RNA sequencing in four patients with advanced PC to identify molecular alterations that could guide clinical management. In two cases, the genomic and transcriptomic profiles provided targets for experimental therapies that resulted in biochemical response and prolonged disease stabilization: (i) immune checkpoint inhibition with pembrolizumab based on high tumor mutational burden and a single-base substitution signature associated with APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) overactivation; (ii) multi-receptor tyrosine kinase inhibition with lenvatinib due to overexpression of FGFR1 and RET and, later in the course of disease, PARP inhibition with olaparib prompted by signs of defective homologous recombination DNA repair. In addition, our data provided new insights into the molecular landscape of PC with respect to the genome-wide footprints of specific mutational processes and pathogenic germline alterations. These data underscore the potential of comprehensive molecular analyses to improve care for patients with ultra-rare cancers based on insight into disease biology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-09T14:20:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006748","title":"DERMATLAS__Malignant_proliferating_pilar_tumour_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Malignant proliferating pilar tumours.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Malignant proliferating pilar tumours.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006749","title":"DERMATLAS__Cellular_neurothekeoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Cellular neurothekeomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Cellular neurothekeomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006750","title":"DERMATLAS__Cellular_neurothekeoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Cellular neurothekeomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Cellular neurothekeomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006751","title":"DERMATLAS__Myoepithelial_carcinoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Myoepithelial carcinomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Myoepithelial carcinomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006752","title":"DERMATLAS__Myoepithelial_carcinoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Myoepithelial carcinomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Myoepithelial carcinomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006753","title":"DERMATLAS__Pilomatrix_carcinoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Pilomatrix carcinomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Pilomatrix carcinomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006754","title":"DERMATLAS__Pilomatrix_carcinoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Pilomatrix carcinomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Pilomatrix carcinoma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006755","title":"Human pan-cancer plasma cfRNA study - raw data","description":"This study contains mRNA capture sequencing data from plasma of 266 different human donors. The first, pan-cancer, cohort covers 25 high-grade to metastatic cancer types (8 cancer patients per type) and a control group (8 healthy donors). The validation cohort comprises additional plasma samples from ovarian, prostate and uterine cancer patients (12 per type) as well as additional samples from controls (22 new and 8 repeated). \nSamples were sequenced on a NovaSeq 6000 and are provided in FASTQ format.","abstract":"This study contains mRNA capture sequencing data from plasma of 266 different human donors. The first, pan-cancer, cohort covers 25 high-grade to metastatic cancer types (8 cancer patients per type) and a control group (8 healthy donors). The validation cohort comprises additional plasma samples from ovarian, prostate and uterine cancer patients (12 per type) as well as additional samples from controls (22 new and 8 repeated). \nSamples were sequenced on a NovaSeq 6000 and are provided in FASTQ format.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-10T10:31:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006756","title":"Exome_NanoSeq__Salivary_Gland_","description":"Whole Exome NanoSeq in minor salivary gland samples from subjects with Primary Sjogrens' Syndrome (PSS) and controls. PSS samples contain regions of lymphocyte infiltration, which will be dissected using the LCM and sequenced separately from the remaining tissue.","abstract":"Investigating the mutation landscape of the minor salivary glands in Primary Sjogrens' Syndrome and healthy controls using novel NanoSeq (Duplex) technology.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006757","title":"Enrichment of oral-derived bacteria in inflamed colorectal tumors and distinct associations of Fusobacterium in the mesenchymal subtype","description":"The association between colorectal cancer (CRC) clinical variables and Fusobacterium, but not other intra-tumoral bacteria, has been extensively studied. Here we leveraged whole-transcriptome sequencing from 807 CRC tumor samples from the AVANT phase III trial to dually characterize tumor gene expression and intra-tumoral bacteria. After stringent filtering, 74 high-confidence taxa were identified. 17 of these species, including 4 Fusobacterium spp., were classified as orally-derived and had a robust signal within right-sided, MSI-H, and BRAF mutant tumors. Across consensus molecular subtypes (CMS), integration of Fusobacterium animalis presence and tumor gene expression revealed that F. animalis had the greatest number of associations in mesenchymal CMS4 tumors, despite an overall lower prevalence than in immune CMS1 tumors. Pathway analysis within CMS4 revealed that F. animalis, but not other highly prevalent species, was uniquely associated with pathways for collagen degradation and formation as well as IL-6 and IL-1 cytokine signaling. These associations could explain in part why Fusobacterium has been previously associated with reduced survival in mesenchymal populations. Overall, this study identified oral-derived bacteria, including Fusobacterium, as broadly more prevalent in inflamed CRC tumors compared to the other subtypes, and the association of intra-tumoral bacteria on tumor gene expression is context- and species-specific.","abstract":"The association between colorectal cancer (CRC) clinical variables and Fusobacterium, but not other intra-tumoral bacteria, has been extensively studied. Here we leveraged whole-transcriptome sequencing from 807 CRC tumor samples from the AVANT phase III trial to dually characterize tumor gene expression and intra-tumoral bacteria. After stringent filtering, 74 high-confidence taxa were identified. 17 of these species, including 4 Fusobacterium spp., were classified as orally-derived and had a robust signal within right-sided, MSI-H, and BRAF mutant tumors. Across consensus molecular subtypes (CMS), integration of Fusobacterium animalis presence and tumor gene expression revealed that F. animalis had the greatest number of associations in mesenchymal CMS4 tumors, despite an overall lower prevalence than in immune CMS1 tumors. Pathway analysis within CMS4 revealed that F. animalis, but not other highly prevalent species, was uniquely associated with pathways for collagen degradation and formation as well as IL-6 and IL-1 cytokine signaling. These associations could explain in part why Fusobacterium has been previously associated with reduced survival in mesenchymal populations. Overall, this study identified oral-derived bacteria, including Fusobacterium, as broadly more prevalent in inflamed CRC tumors compared to the other subtypes, and the association of intra-tumoral bacteria on tumor gene expression is context- and species-specific.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-11T16:55:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006758","title":"The Iberian Roma genetic variant server","description":"The Roma are the most numerous ethnic minority in Europe. The Iberian Roma arrived in the Iberian Peninsula five centuries ago and still today, they keep a strong group identity. Demographic and cultural reasons lie behind a high rate of Mendelian disease often related to founder variants. We have analysed exome data from 119 Iberian Roma individuals collected from 2018 to 2020. A database of variant frequency has been implemented (IRPVS) and made available online. We have analysed the carrier rate of founder private alleles as well as pathogenic variants present in the general population. Significant enrichment in structural variants involving gene clusters related to keratinization and epidermal growth suggest that evolutive mechanisms have developed towards climate and environmental adaptation. IRPVS can be accessed at http://irpvs.clinbioinfosspa.es/","abstract":"The Roma are the most numerous ethnic minority in Europe. The Iberian Roma arrived in the Iberian Peninsula five centuries ago and still today, they keep a strong group identity. Demographic and cultural reasons lie behind a high rate of Mendelian disease often related to founder variants. We have analysed exome data from 119 Iberian Roma individuals collected from 2018 to 2020. A database of variant frequency has been implemented (IRPVS) and made available online. We have analysed the carrier rate of founder private alleles as well as pathogenic variants present in the general population. Significant enrichment in structural variants involving gene clusters related to keratinization and epidermal growth suggest that evolutive mechanisms have developed towards climate and environmental adaptation. IRPVS can be accessed at http://irpvs.clinbioinfosspa.es/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-11T17:03:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006759","title":"Neutrophil extracellular traps have auto-catabolic activity and produce mononucleosome-associated circulating DNA","description":null,"abstract":"Because circulating DNA (cirDNA) are mainly detected as mononucleosome-associated circulating DNA (mono-N cirDNA) in blood apoptosis has until now been considered as the main source of cirDNA. The mechanism of cirDNA release into the circulation, however, is still not fully understood. This work addresses that knowledge gap, working from the postulate that neutrophil extracellular traps (NET) may be a source of cirDNA, and by investigating whether NET may directly produce mono-N cirDNA","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-13T17:22:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006760","title":"DERMATLAS__Malignant_proliferating_pilar_tumour_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Malignant proliferating pilar tumours.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Malignant proliferating pilar tumours.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006761","title":"DERMATLAS__Malignant_proliferating_pilar_tumour_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Malignant proliferating pilar tumours.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Malignant proliferating pilar tumours.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006762","title":"Single-cell transcriptomics identifies pathogenic T-helper 17.1 cells and pro-inflammatory monocytes in ICI-related pneumonitis","description":"ICI-pneumonitis is a frequent serious adverse event of cancer immunotherapy hinging on a cell-mediated immune response, though the exact pathophysiology is currently unknown. Using single-cell transcriptomics, an enrichment of pathogenic (TBX21, RORC, IFNG, IL17A, CSF2 expressing) T-helper 17.1 cells and pro-inflammatory (TNF, IL1B, IL6, IL23A expressing) monocytes was identified in ICI-pneumonitis bronchoalveolar lavage fluid, putatively engaging in a feedforward inflammatory loop. This finding yields several novel therapeutic targets for the treatment of ICI-pneumonitis. Most notably repurposing anti-IL-23 merits further research as a potential efficacious and safe treatment for ICI-pneumonitis.","abstract":"ICI-pneumonitis is a frequent serious adverse event of cancer immunotherapy hinging on a cell-mediated immune response, though the exact pathophysiology is currently unknown. Using single-cell transcriptomics, an enrichment of pathogenic (TBX21, RORC, IFNG, IL17A, CSF2 expressing) T-helper 17.1 cells and pro-inflammatory (TNF, IL1B, IL6, IL23A expressing) monocytes was identified in ICI-pneumonitis bronchoalveolar lavage fluid, putatively engaging in a feedforward inflammatory loop. This finding yields several novel therapeutic targets for the treatment of ICI-pneumonitis. Most notably repurposing anti-IL-23 merits further research as a potential efficacious and safe treatment for ICI-pneumonitis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-14T10:51:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006763","title":"We used genome-wide SNP data to understand the population and language contact situation between several ethnolinguistic groups in Northwestern Amazonia (NWA)","description":null,"abstract":"Provide new insights about the population history of NWA\nUnderstand the impacts of extensive population contact on patterns of genome-wide diversity patterns","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006764","title":"HCA_Commercial_iPSCS_PBMCs_Haniffa_RNA","description":"Single cell sequencing of skin organoids derived from commercial iPSCS with introduced PBMCs","abstract":"Single cell sequencing of skin organoids derived from commercial iPSCS with introduced PBMCs","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006765","title":"HCA_Commercial_iPSCS_PBMCs_Haniffa_Spatial","description":"Spatial single cell sequencing of skin organoids derived from commercial iPSCS with introduced PBMCs","abstract":"Spatial single cell sequencing of skin organoids derived from commercial iPSCS with introduced PBMCs","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006766","title":"Mechanisms of measurable residual disease resistance (MRD)  by comparing the transcriptional and genomic profiles of paired leukemic cells at diagnosis and after treatment","description":null,"abstract":"Failure to achieve complete response (CR) and the persistence of measurable residual disease (MRD) is associated with inferior survival in acute myeloid leukemia (AML). A better understanding of why therapies are unable to eradicate these residual leukemic cells could be relevant, particularly in elderly AML for which outcomes remain dismal despite increasing CR rates with novel combinations. However, there is virtually no data on the molecular traits of tumor cells persisting in patients achieving less than CR and those in CR but positive MRD (CR/MRD+). We analyzed mechanisms of resistance by comparing the transcriptional and genomic profile of paired leukemic cells at diagnosis and after treatment with semi-intensive chemotherapy or a hypomethylating agent, in patients achieving partial remission (PR) and CR/MRD+. To our knowledge, deep profiling of MRD cells has not been performed in elderly AML, and our results identified deregulated genes and recurrent mutations with limited or previously unknown role in AML pathobiology, which were associated with treatment resistance and inferior survival.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006767","title":"Data containing genome-wide SNP data from Northwestern Amazonia","description":"Provide new insights about the population history of NWA and identify the impact of intense population contact on patterns of genetic variation","abstract":"Provide new insights about the population history of NWA and identify the impact of intense population contact on patterns of genetic variation","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-14T13:42:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006768","title":"DERMATLAS__Proliferating_pilar_tumour_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are proliferating pilar tumours.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are proliferating pilar tumours.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006769","title":"BCR-ABL is enriched in S- and G2-cell cycle phases","description":"To address the unusually long duration of imatinib therapy for chronic myelogenous leukemia, we sought to understand the expression of BCR-ABL gene expression with different phases of the cell cycle.  A precedent for dynamic fusion oncoprotein expression already exists for the pediatric solid tumor, rhabdomyosarcoma.  Quantitative immunocytochemistry was conducted to compare the expression of BCR-ABL with markers of each cell cycle phase: CDK6 for G1, CDK2 for S, phospho-CDC2 for G2, and phospho-HH3 for M phase.  BCR-ABL expression was most strongly correlated with the G2 and S cell cycle phases.  Low BCR-ABL expression only coincided with high cell cycle marker expression for the G1.  BCR-ABL was rarely if at all expressed in M.  Our results suggest a possible explanation for the prolonged nature of imatinib therapy, which may be only effective on S- and G2-phase actively replicating leukemia cells.","abstract":"To address the unusually long duration of imatinib therapy for chronic myelogenous leukemia, we sought to understand the expression of BCR-ABL gene expression with different phases of the cell cycle.  A precedent for dynamic fusion oncoprotein expression already exists for the pediatric solid tumor, rhabdomyosarcoma.  Quantitative immunocytochemistry was conducted to compare the expression of BCR-ABL with markers of each cell cycle phase: CDK6 for G1, CDK2 for S, phospho-CDC2 for G2, and phospho-HH3 for M phase.  BCR-ABL expression was most strongly correlated with the G2 and S cell cycle phases.  Low BCR-ABL expression only coincided with high cell cycle marker expression for the G1.  BCR-ABL was rarely if at all expressed in M.  Our results suggest a possible explanation for the prolonged nature of imatinib therapy, which may be only effective on S- and G2-phase actively replicating leukemia cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-14T20:29:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006770","title":"Whole_exome_sequencing__LCM_Buccal_","description":"Laser capture microdissection of oral mucosa samples to identify somatic mutations, mutational signatures and copy number and structural variation.","abstract":"Laser capture microdissection of oral mucosa samples to identify somatic mutations, mutational signatures and copy number and structural variation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006771","title":"The BAF chromatin remodeling complex is a novel target of spliceosome dysregulation in SF3B1-mutated chronic lymphocytic leukemia","description":null,"abstract":"SF3B1 mutations are recurrent genetic aberrations in chronic lymphocytic leukemia (CLL) that are particularly enriched in the clinically aggressive stereotyped subset #2. To elucidate the effect of SF3B1 mutations on splicing, we performed RNA-sequencing on 100 CLL subset cases, including 35 subset #2 cases. Zooming in on subset #2, we identified 61 differentially expressed splicing events when comparing 17 SF3B1mut to 18 SF3B1wt cases. A key event concerned the inclusion of an alternative exon in BRD9, a BAF chromatin remodeling complex component. We also detected alternative splicing in 5 additional transcripts related to the BAF complex: ZEB1, PLSCR1, PAPD5, DCAF16, and DLST. Long-read RNA-sequencing confirmed these alternative splice transcripts. In conclusion, spliceosome dysregulation caused by mutated SF3B1 leads to multiple splicing events and altered BAF complex function, highlighting a potential novel therapeutic vulnerability in SF3B1mut CLL.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-15T10:27:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006772","title":"S3 Swedish schizophrenia case-control study","description":null,"abstract":"Genome-wide case-control association study in Sweden, with the aim to study the genetic basis of schizophrenia risk, disease severity and treatment resistance, as well as the interplay with environmental risk factors. The study cohort includes array-based data from whole blood-DNA. Population-based sampling was used to recruit cases with schizophrenia, based on data from the Swedish national patient register, as well as controls who had never been hospitalized for schizophrenia or bipolar disorder.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-15T13:40:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006773","title":"HCA_Lung_Adult_AO_Respire_Teichmann_RNA_Managed_Access_","description":"This project seeks to understand the link between T cell activation, effector function and cellular metabolism using single cell RNA sequencing and ATAC sequencing. Specifically this project focuses on immune responses in lung resident T cells and circulating T cells from healthy and asthmatic controls by activating with TCR and co-stimulation/cytokines relevant for asthma prior to sequencing.","abstract":"Dysregulated immune responses are a hallmark of inflammatory diseases such as asthma. The effector functions of immune cells, particularly T cells, are enabled and coordinated by metabolic changes. ","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006774","title":"MutWP1__CRUK_Grand_Challenge__matched_blood_Nanoseq","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-15T14:20:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006775","title":"Whole Genome Sequencing Data of High Grade Serous Ovarian Cancer","description":"Longitudinal whole genome sequencing data to study chemoresponse in ovarian cancer. These samples belong to an ongoing sample collection and the data already includes hundreds of samples from over 200 patients. Samples are from primary and metastatic tissues and ascites. All patients have been treated with platinum-taxane based chemotherapy and majority of them are diagnosed with high-grade serous ovarian cancer.","abstract":"Longitudinal whole genome sequencing data to study chemoresponse in ovarian cancer. These samples belong to an ongoing sample collection and the data already includes hundreds of samples from over 200 patients. Samples are from primary and metastatic tissues and ascites. All patients have been treated with platinum-taxane based chemotherapy and majority of them are diagnosed with high-grade serous ovarian cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-16T08:29:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006776","title":"Mitochondrial_DNA_copy_number_of_haematopoietic_cells__post_natal_","description":"Low coverage WGS (likely as low as 0.5X or below) could theoretically be used to infer the average mitochondrial copy number per cell of normal diploid cells. This will be applied to homogenous populations of haematopoietic stem cells and progenitors at different points during development/ adult life. In this study we will only look at post-natal samples i.e. cord blood and later.","abstract":"In Well-functioning mitochondria are of vital importance to maintaining haematopoietic stem cell function.  Understanding the number of copies of the mitochondrial DNA genome - and related to this, the number of mitochondria - is therefore of importance to understanding how mitochondrial copy number is maintained and regulated through life and different stages of haematopoietic differentiation.  This may also inform interpretation of mitochondrial DNA copy number estimates from single-cell derived colonies that have undergone differentiation.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006777","title":"consHLA: a Next Generation Sequencing Consensus-based HLA Typing Workflow Optimised for Pediatric Cancer Patients","description":null,"abstract":"Serology assays are current HLA typing standards, but gene sequencing could provide greater accuracy. Cancer patient care increasingly employs whole genome sequencing (WGS) and RNA sequencing (RNA-seq) data, making these datasets also available for typing. In such patients WGS and RNA-seq could provide independent datasets that could be combined to increase HLA typing accuracy and confidence, and profile HLA gene mutations and expression. We thus constructed a workflow that analyses these datasets for cancer patient HLA typing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006778","title":"Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence","description":"Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we perform longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. Strikingly, we observe that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19.","abstract":"Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we perform longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. Strikingly, we observe that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-17T09:33:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006779","title":"Host pathogen interaction long read transcriptome","description":"Our incomplete knowledge of the human transcriptome impairs the detection of disease-causing variants, in particular in transcripts only expressed under certain conditions. These transcripts are often lacking from reference transcript sets, such as Ensembl/GENCODE and RefSeq, and could be relevant for establishing genetic diagnoses. We present SUsPECT (Solving Unsolved Patient Exomes/gEnomes using Custom Transcriptomes), a pipeline based on the Ensembl Variant Effect Predictor (VEP) to predict variant impact on custom transcript sets, such as those generated by long-read RNA-sequencing, for downstream prioritization. Our pipeline predicts the functional consequence and likely deleteriousness scores for missense variants in the context of novel open reading frames predicted from any transcriptome. We demonstrate the utility of SUsPECT by uncovering potential mutational mechanisms of pathogenic variants in ClinVar that are predicted to be benign using the reference transcript annotation. In further support of SUsPECT’s utility, we identified an enrichment of immune-related variants predicted to have a more severe molecular consequence when annotating with a newly generated transcriptome from stimulated immune cells instead of the reference transcriptome. Our pipeline outputs crucial information for further prioritization of potentially disease-causing variants for any disease and will become increasingly useful as more long-read RNA sequencing datasets become available.","abstract":"Our incomplete knowledge of the human transcriptome impairs the detection of disease-causing variants, in particular in transcripts only expressed under certain conditions. These transcripts are often lacking from reference transcript sets, such as Ensembl/GENCODE and RefSeq, and could be relevant for establishing genetic diagnoses. We present SUsPECT (Solving Unsolved Patient Exomes/gEnomes using Custom Transcriptomes), a pipeline based on the Ensembl Variant Effect Predictor (VEP) to predict variant impact on custom transcript sets, such as those generated by long-read RNA-sequencing, for downstream prioritization. Our pipeline predicts the functional consequence and likely deleteriousness scores for missense variants in the context of novel open reading frames predicted from any transcriptome. We demonstrate the utility of SUsPECT by uncovering potential mutational mechanisms of pathogenic variants in ClinVar that are predicted to be benign using the reference transcript annotation. In further support of SUsPECT’s utility, we identified an enrichment of immune-related variants predicted to have a more severe molecular consequence when annotating with a newly generated transcriptome from stimulated immune cells instead of the reference transcriptome. Our pipeline outputs crucial information for further prioritization of potentially disease-causing variants for any disease and will become increasingly useful as more long-read RNA sequencing datasets become available.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-17T12:41:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006780","title":"Single-cell RNA and ATAC sequencing data analysis of human postmenopausal fallopian tube and ovary","description":"In this study, we used a combination of technologies, including Drop-seq, 10X single-cell RNA-seq (scRNA-seq), and single-cell assay on transposase accessible chromatin (scATAC-seq) to generate  a high-quality cell atlas that consists of four tissue sites from the reproductive tract of postmenopausal women. This atlas, by far the most comprehensive map of the postmenopausal female reproductive system to date, will pave the way to a better understanding of the pathophysiology of many diseases affecting older women.","abstract":"In this study, we used a combination of technologies, including Drop-seq, 10X single-cell RNA-seq (scRNA-seq), and single-cell assay on transposase accessible chromatin (scATAC-seq) to generate  a high-quality cell atlas that consists of four tissue sites from the reproductive tract of postmenopausal women. This atlas, by far the most comprehensive map of the postmenopausal female reproductive system to date, will pave the way to a better understanding of the pathophysiology of many diseases affecting older women.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-17T15:08:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006781","title":"Tertiary lymphoid structure signatures are associated with immune checkpoint inhibitor related acute interstitial nephritis","description":null,"abstract":"Tertiary lymphoid structures (TLSs) are associated with anti-tumor response following immune checkpoint inhibitor (ICI) therapy, but a commensurate observation of TLS is absent for immune related adverse events (irAEs) i.e. acute interstitial nephritis (AIN). \nWe hypothesized that TLS-associated inflammatory gene signatures are present in AIN and performed NanoString-based gene expression and multiplex 12-chemokine profiling on paired kidney tissue, urine and plasma specimens of 36 participants who developed acute kidney injury (AKI) on ICI therapy: AIN (18), acute tubular necrosis (9), or HTN nephrosclerosis (9). Increased T and B cell scores, a Th1-CD8+ T cell axis accompanied by interferon- and TNF superfamily signatures were detected in the ICI-AIN group. TLS signatures were significantly increased in AIN cases and supported by histopathological identification","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-17T16:59:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006782","title":"PDAC organoid genomic heterogeneity","description":"The establishment of patient-derived pancreatic cancer organoid culture in recent years creates an exciting opportunity for researchers to perform a wide range of in vitro studies on a model that closely recapitulates the tumor. Among the outstanding questions in pancreatic cancer biology are the causes and consequences of genomic heterogeneity observed in the disease. However, to use pancreatic cancer organoids as a model to study genomic variations, we need to first understand the degree of genomic heterogeneity and its stability within organoids. Here, we used single-cell whole-genome sequencing to investigate the genomic heterogeneity of two independent pancreatic cancer organoids, as well as their genomic stability with extended culture. Clonal populations with similar copy number profiles were observed within the organoids, and the proportion of these clones was shifted with extended culture, suggesting the growth advantage of some clones. However, sub-clonal genomic heterogeneity was also observed within each clonal population, indicating the genomic instability of the pancreatic cancer cells themselves. Furthermore, our transcriptomic analysis also revealed a positive correlation between copy number alterations and gene expression regulation, suggesting the “gene dosage” effect of these copy number alterations that translates to gene expression regulation.","abstract":"The establishment of patient-derived pancreatic cancer organoid culture in recent years creates an exciting opportunity for researchers to perform a wide range of in vitro studies on a model that closely recapitulates the tumor. Among the outstanding questions in pancreatic cancer biology are the causes and consequences of genomic heterogeneity observed in the disease. However, to use pancreatic cancer organoids as a model to study genomic variations, we need to first understand the degree of genomic heterogeneity and its stability within organoids. Here, we used single-cell whole-genome sequencing to investigate the genomic heterogeneity of two independent pancreatic cancer organoids, as well as their genomic stability with extended culture. Clonal populations with similar copy number profiles were observed within the organoids, and the proportion of these clones was shifted with extended culture, suggesting the growth advantage of some clones. However, sub-clonal genomic heterogeneity was also observed within each clonal population, indicating the genomic instability of the pancreatic cancer cells themselves. Furthermore, our transcriptomic analysis also revealed a positive correlation between copy number alterations and gene expression regulation, suggesting the “gene dosage” effect of these copy number alterations that translates to gene expression regulation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-20T10:31:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006783","title":"The genomic landscape of acute lymphoblastic leukemia with intrachromosomal amplification of chromosome 21","description":null,"abstract":"Use single cell whole genome sequencing data from one iAMP21 patient to study the clonal evolution of iAMP21.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006784","title":"Leukemia sequencing study","description":"A custom single-cell amplicon DNA sequencing panel was designed to cover relevant somatic mutations and common single nucleotide polymorphisms (panel CO303).\nFrozen bone marrow mononuclear cells were thawed, stained using the antibody-derived tags panel TotalSeq™-D Human Heme Oncology Cocktail, V1.0 (Biolegend) and loaded into Tapestri single-cell DNA genotyping platform (Mission Bio) to perform microfluidic encapsulation, lysis, and barcoding according to the manufacturer’s protocol (Chemistry V2, PN_3360A). \nDNA and ADT libraries were prepared and underwent 2x150bp paired-end sequencing on a NextSeq 500 platform (Illumina).","abstract":"A custom single-cell amplicon DNA sequencing panel was designed to cover relevant somatic mutations and common single nucleotide polymorphisms (panel CO303).\nFrozen bone marrow mononuclear cells were thawed, stained using the antibody-derived tags panel TotalSeq™-D Human Heme Oncology Cocktail, V1.0 (Biolegend) and loaded into Tapestri single-cell DNA genotyping platform (Mission Bio) to perform microfluidic encapsulation, lysis, and barcoding according to the manufacturer’s protocol (Chemistry V2, PN_3360A). \nDNA and ADT libraries were prepared and underwent 2x150bp paired-end sequencing on a NextSeq 500 platform (Illumina).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-21T17:06:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006785","title":"Integrative analysis of exome-seq, RNA-seq, ATAC-seq (bulk and single-cell), and Hi-C data generated from 3-D spatially mapped samples acquired during surgical resection from 10 patients diagnosed with IDH-WT glioblastoma","description":"Glioblastoma (GBM), the most common primary brain cancer in adults, remains incurable with no targeted therapies approved despite decades of investigation into its molecular landscape. Treatment failure is attributed to intratumoral heterogeneity in the GBM genome and epigenome, which foster tumor evolution and selection of resistant clones. However, tumor evolution and intratumoral heterogeneity remain poorly understood on the level of the whole tumor as most studies are based on single samples per patient and lack spatial context. Here, we have used 3-D neuronavigation during surgical resection for 10 primary IDH-WT GBM patients to collect 102 samples representing maximal tumor diversity, each mapped by 3-D spatial coordinates. We have applied a strategic set of genomic and epigenomic assays spanning multiple levels of resolution to discover, orthogonally validate, and functionally assess drivers of tumor evolution and intratumoral heterogeneity. These include extrachromosomal DNA amplifications, chromothripsis events, inversions, and translocations that disrupt both the GBM genome and epigenome while generating fusion transcripts and opportunities for therapeutic intervention. We define epigenomic programs that contribute to GBM evolution and intratumoral heterogeneity, revealing their 3-D spatial patterning within whole tumors and their cell type(s) of origin in single-cell data from the same tumor samples. Notably, we distinguish neuronal, glial, and immune programs aberrantly active in tumor cells from their counterparts in normal cells and discover NEUROD1, JUN/FOS, and NF1 transcription factors as key drivers of GBM evolution and growth. Collectively, these data provide unprecedented insight into GBM evolution and intratumoral heterogeneity from single-cell to whole-tumor resolution, redefining current understanding and providing a rich resource of targets for therapeutic investigation.","abstract":"Glioblastoma (GBM), the most common primary brain cancer in adults, remains incurable with no targeted therapies approved despite decades of investigation into its molecular landscape. Treatment failure is attributed to intratumoral heterogeneity in the GBM genome and epigenome, which foster tumor evolution and selection of resistant clones. However, tumor evolution and intratumoral heterogeneity remain poorly understood on the level of the whole tumor as most studies are based on single samples per patient and lack spatial context. Here, we have used 3-D neuronavigation during surgical resection for 10 primary IDH-WT GBM patients to collect 102 samples representing maximal tumor diversity, each mapped by 3-D spatial coordinates. We have applied a strategic set of genomic and epigenomic assays spanning multiple levels of resolution to discover, orthogonally validate, and functionally assess drivers of tumor evolution and intratumoral heterogeneity. These include extrachromosomal DNA amplifications, chromothripsis events, inversions, and translocations that disrupt both the GBM genome and epigenome while generating fusion transcripts and opportunities for therapeutic intervention. We define epigenomic programs that contribute to GBM evolution and intratumoral heterogeneity, revealing their 3-D spatial patterning within whole tumors and their cell type(s) of origin in single-cell data from the same tumor samples. Notably, we distinguish neuronal, glial, and immune programs aberrantly active in tumor cells from their counterparts in normal cells and discover NEUROD1, JUN/FOS, and NF1 transcription factors as key drivers of GBM evolution and growth. Collectively, these data provide unprecedented insight into GBM evolution and intratumoral heterogeneity from single-cell to whole-tumor resolution, redefining current understanding and providing a rich resource of targets for therapeutic investigation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-21T22:06:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006786","title":"Frequencies of variants in the Danish population","description":null,"abstract":"Complimation of variants calls from three idependent cohorts, allowing for calls of rare and common vairants. All samples derived from a Danish research projects with recruitment of individuals of Danish origin (N&gt; 8000). \nMinor allele counts below 5 are masked to keep information de-identified level s.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-22T09:33:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006787","title":"scRNAseq and scATACseq of placebo controlled-trial on MMR non-specific effects","description":"The project includes sequencing data of isolated PBMCs extracted from donors that received the MMR vaccine and donors that received placebo, both containg samples before and after the vaccine.\nIn total, 6 MMR-vaccinated and 6 Placebo donors for both timepoints were included in the scRNAseq data.\nIn total, 12 MMR-vaccinated and 12 Placebo donors for both timepoints were included in the scATACseq data.\n\nThe main goal of the project is studying the non-specific effects of the vaccine and its possible use as an inducer of trained immunity in vivo.","abstract":"The project includes sequencing data of isolated PBMCs extracted from donors that received the MMR vaccine and donors that received placebo, both containg samples before and after the vaccine.\nIn total, 6 MMR-vaccinated and 6 Placebo donors for both timepoints were included in the scRNAseq data.\nIn total, 12 MMR-vaccinated and 12 Placebo donors for both timepoints were included in the scATACseq data.\n\nThe main goal of the project is studying the non-specific effects of the vaccine and its possible use as an inducer of trained immunity in vivo.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-22T12:51:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006788","title":"Transcriptional_reprogramming_from_innate_immune_functions_to_a_pro_thrombotic_signature_upon_SARS_CoV_2_sensing_by_monocytes_in_COVID_19","description":"Alterations in the myeloid immune compartment have been observed in COVID-19, but the specific mechanisms underlying these impairments are not completely understood. Here we examined the functionality of classical CD14+ monocytes as a main myeloid cell component in well-defined cohorts of patients with mild and moderate COVID-19 during the acute phase of infection and compared them to that of healthy individuals. We found that ex vivo isolated CD14+ monocytes from mild and moderate COVID-19 patients display specific expression patterns of costimulatory and inhibitory receptors that clearly distinguish them from healthy monocytes, as well as an altered metabolic profile. In addition, decreased NFB activation in COVID-19 monocytes ex vivo is accompanied by an intact type I IFN antiviral response. Secondary pathogen sensing ex vivo led to a state of functional unresponsiveness characterized by a defect in pro-inflammatory cytokine expression, NFB-driven cytokine responses and defective type I IFN response in moderate COVID-19 monocytes, together with defects in the metabolic reprogramming that innate immune cells usually undergo upon pathogen sensing. Transcriptionally and functionally, COVID-19 monocytes switched their gene expression signature from canonical innate immune functions to a pro-thrombotic phenotype characterized by enrichment of pathways involved in hemostasis, immunothrombosis, platelet aggregation and other accessory pathways to platelet activation, accumulation and clot formation, including extracellular matrix reorganization, integrin cell surface interactions and signaling by PDGF. These results provide a potential mechanism by which innate immune dysfunction in COVID-19 may contribute to disease pathology","abstract":"Alterations in the myeloid immune compartment have been observed in COVID-19, but the specific mechanisms underlying these impairments are not completely understood. Here we examined the functionality of classical CD14+ monocytes as a main myeloid cell component in well-defined cohorts of patients with mild and moderate COVID-19 during the acute phase of infection and compared them to that of healthy individuals. We found that ex vivo isolated CD14+ monocytes from mild and moderate COVID-19 patients display specific expression patterns of costimulatory and inhibitory receptors that clearly distinguish them from healthy monocytes, as well as an altered metabolic profile. In addition, decreased NFB activation in COVID-19 monocytes ex vivo is accompanied by an intact type I IFN antiviral response. Secondary pathogen sensing ex vivo led to a state of functional unresponsiveness characterized by a defect in pro-inflammatory cytokine expression, NFB-driven cytokine responses and defective type I IFN response in moderate COVID-19 monocytes, together with defects in the metabolic reprogramming that innate immune cells usually undergo upon pathogen sensing. Transcriptionally and functionally, COVID-19 monocytes switched their gene expression signature from canonical innate immune functions to a pro-thrombotic phenotype characterized by enrichment of pathways involved in hemostasis, immunothrombosis, platelet aggregation and other accessory pathways to platelet activation, accumulation and clot formation, including extracellular matrix reorganization, integrin cell surface interactions and signaling by PDGF. These results provide a potential mechanism by which innate immune dysfunction in COVID-19 may contribute to disease pathology.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-22T14:06:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006789","title":"The molecular landscape of homologous recombination deficient, end-stage, high grade serous ovarian cancer","description":"High grade serous ovarian cancer (HGSC) is frequently characterized by homologous recombination (HR) DNA repair deficiency, and while most such tumors are sensitive to initial treatment, acquired resistance is common. We undertook a multi-omics approach to interrogating mechanisms of resistance, using multiple autopsy samples collected from 15 women with HR-deficient HGSC.","abstract":"High grade serous ovarian cancer (HGSC) is frequently characterized by homologous recombination (HR) DNA repair deficiency, and while most such tumors are sensitive to initial treatment, acquired resistance is common. We undertook a multi-omics approach to interrogating mechanisms of resistance, using multiple autopsy samples collected from 15 women with HR-deficient HGSC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-23T08:13:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006790","title":"BRCA2 GERMLINE MUTATIONS IDENTIFY GASTRIC CANCERS RESPONSIVE TO OLAPARIB","description":null,"abstract":"Treatment with PARP inhibitors (PARPi) has been approved in some tumors bearing a deficient Homologous Recombination (HR) system. Gastric cancer exhibits a mutational signature associated with HR failure in 7-12% of cases, suggesting that these patients might benefit from PARPi. We aimed at verifying whether a PARPi regimen may represent a window of opportunity for selected gastric cancer patients with loss-of-function mutations in genes of the HR pathway. Cell viability assays and preclinical trials showed that olaparib treatment was effective in  patient-derived xenografts (PDXs) harboring BRCA2 germline mutations and somatic inactivation of the second allele. Moreover, evaluation of HR deficiency and mutational signatures efficiently stratified responder vs non-responder PDXs.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006791","title":"DNA methylation atlas of normal human cell types","description":"DNA methylation is a fundamental epigenetic mark that governs chromatin organization, cell identity, and gene expression. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples.\nReplicates of the same cell-type are &gt;99.5% identical, demonstrating robustness of cell identity programs to genetic variation and environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny, and identifies methylation patterns retained since gastrulation. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hyper-methylated loci are rare and are enriched for CpG islands, polycomb targets, and CTCF binding sites, suggesting a novel role in shaping cell type-specific chromatin looping. The atlas provides an essential resource for interpretation of disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.","abstract":"DNA methylation is a fundamental epigenetic mark that governs chromatin organization, cell identity, and gene expression. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples.\nReplicates of the same cell-type are &gt;99.5% identical, demonstrating robustness of cell identity programs to genetic variation and environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny, and identifies methylation patterns retained since gastrulation. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hyper-methylated loci are rare and are enriched for CpG islands, polycomb targets, and CTCF binding sites, suggesting a novel role in shaping cell type-specific chromatin looping. The atlas provides an essential resource for interpretation of disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-23T11:23:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006792","title":"Targeted Resequencing of Otosclerosis Patients from Different Populations Replicates Results from a Previous Genome-Wide Association Study","description":null,"abstract":"Otosclerosis is one of the most common causes of hearing loss in young adults. It has a prevalence of 0.3–0.4% in the European population. Clinical symptoms usually occur between the second and fifth decade of life. Different studies have been performed to unravel the genetic architecture of the disease. Recently, a genome-wide association study (GWAS) identified 15 novel risk loci and replicated the regions of three previously reported candidate genes. In this study, seven candidate genes from the GWAS were resequenced using single molecule molecular inversion probes (smMIPs). smMIPs were used to capture the exonic regions and the 3′ and 5′ untranslated regions (UTR). Discovered variants were tested for association with the disease using single variant and gene-based association analysis. The single variant results showed that 13 significant variants were associated with otosclerosis. Associated variants were found in five of the seven genes studied here, including AHSG, LINC01482, MARK3, SUPT3H and RELN. Conversely, burden testing did not show a major role of rare variants in the disease. In conclusion, this study was able to replicate five out of seven candidate genes reported in the previous GWAS. This association is likely mainly driven by common variants.","study_type":"Resequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006793","title":"Molecular heterogeneity and commonalities in pancreatic cancer precursors with gastric and intestinal phenotype","description":"Due to the limited number of modifiable risk factors, secondary prevention strategies based on early diagnosis represent the preferred route to improve the prognosis of pancreatic ductal adenocarcinoma (PDAC). Here, we provide a comparative morphogenetic analysis of PDAC precursors aiming at dissecting the process of carcinogenesis and tackling the heterogeneity of preinvasive lesions.","abstract":"Due to the limited number of modifiable risk factors, secondary prevention strategies based on early diagnosis represent the preferred route to improve the prognosis of pancreatic ductal adenocarcinoma (PDAC). Here, we provide a comparative morphogenetic analysis of PDAC precursors aiming at dissecting the process of carcinogenesis and tackling the heterogeneity of preinvasive lesions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-23T15:08:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006794","title":"RNA-sequencing of ex vivo exhausted human antigen-specific T cells","description":"Tumor-specific T cells are frequently exhausted by chronic antigenic stimulation. To explore new pathways for reinvigoration of anti-tumor immune functions, we developed a human ex vivo exhaustion model by repetitive antigenic stimulation of primary CD8 T cells. This results in T cells that resemble patient-derived T cells in tumors on a phenotypic and transcriptional level.","abstract":"Tumor-specific T cells are frequently exhausted by chronic antigenic stimulation. To explore new pathways for reinvigoration of anti-tumor immune functions, we developed a human ex vivo exhaustion model by repetitive antigenic stimulation of primary CD8 T cells. This results in T cells that resemble patient-derived T cells in tumors on a phenotypic and transcriptional level.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-23T16:05:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006795","title":"RNA sequencing of spontaneous migraine attacks","description":null,"abstract":"Migraine is a common, polygenic disorder that is characterized by moderate to severe headache attacks that lasts for 4-72 hours. Migraine attacks are commonly treated with triptans, serotonin receptor agonists. However, the biological mechanisms of triptans are debated. We collected temporal RNA profiles on 24 migraine patients, using blood samples collected at a migraine attack and two hours after treatment with a triptan.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006796","title":"The genomic landscape of acute lymphoblastic leukemia with intrachromosomal amplification of chromosome 21","description":"Use single cell whole genome sequencing data from one iAMP21 patient SJBALL021901 to study the clonal evolution of iAMP21.","abstract":"Use single cell whole genome sequencing data from one iAMP21 patient SJBALL021901 to study the clonal evolution of iAMP21.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-24T12:13:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006797","title":"Shallow whole genome sequencing of tumor samples from SALTO trial","description":"Patients and methods: We analyzed tumor samples of 256 patients enrolled in the SALTO randomized controlled trial (RCT) who were randomized to receive treatments capecitabine or S-1, optionally supplemented with bevacizumab.  Chromosome 18q11.2-q12.1 copy number status was measured and correlated with PFS according to a predefined analysis plan with marker-treatment interaction as the primary end-point.","abstract":"Patients and methods: We analyzed tumor samples of 256 patients enrolled in the SALTO randomized controlled trial (RCT) who were randomized to receive treatments capecitabine or S-1, optionally supplemented with bevacizumab.  Chromosome 18q11.2-q12.1 copy number status was measured and correlated with PFS according to a predefined analysis plan with marker-treatment interaction as the primary end-point.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006798","title":"Single-cell level characterization of B cell depletion and repopulation following rituximab in systemic lupus erythematosus","description":"Rituximab, a CD20+ B cell depletion therapy, is frequently used in the treatment of systemic lupus erythematosus (SLE). However, variability in patient response highlights the need for a deeper understanding of the underlying immune cell dynamics of B cell depletion and repopulation. In this study, we conducted longitudinal single-cell profiling of nine SLE patients treated with rituximab from pretreatment to up to 15 months post-treatment. These were compared to eight healthy controls. We profiled PBMCs via 10X Genomics single-cell RNA, surface protein (CITE-seq), B cell receptor (BCR), and T cell receptor (TCR) sequencing and sequenced bulk BCR repertoires in parallel. For single cell sequencing, 10 pools were created with an equal number of cells from 4 samples each. Samples collected at different timepoints from the same patient were distributed across different pools to allow demultiplexing of individuals using genotypes captured from the scRNA-seq data. Libraries were pooled using a ratio of GEX:CITE:TCR:BCR=9:2:1:1 and were sequenced across two lanes of the NovaSeq 6000. For bulk BCR sequencing, individual samples were demultiplexed using primer barcodes and paired-end BCR amplicon reads were merged prior to submission; data are provided as unmapped single-end reads.\n","abstract":"Rituximab, a CD20+ B cell depletion therapy, is frequently used in the treatment of systemic lupus erythematosus (SLE). However, variability in patient response highlights the need for a deeper understanding of the underlying immune cell dynamics of B cell depletion and repopulation. In this study, we conducted longitudinal single-cell profiling of nine SLE patients treated with rituximab from pretreatment to up to 15 months post-treatment. These were compared to eight healthy controls. We profiled PBMCs via 10X Genomics single-cell RNA, surface protein (CITE-seq), B cell receptor (BCR), and T cell receptor (TCR) sequencing and sequenced bulk BCR repertoires in parallel. For single cell sequencing, 10 pools were created with an equal number of cells from 4 samples each. Samples collected at different timepoints from the same patient were distributed across different pools to allow demultiplexing of individuals using genotypes captured from the scRNA-seq data. Libraries were pooled using a ratio of GEX:CITE:TCR:BCR=9:2:1:1 and were sequenced across two lanes of the NovaSeq 6000. For bulk BCR sequencing, individual samples were demultiplexed using primer barcodes and paired-end BCR amplicon reads were merged prior to submission; data are provided as unmapped single-end reads.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-24T12:54:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006799","title":"Targeted_NanoSeq__LEGACY_cohort_","description":"Targeted NanoSeq of fresh buccal swabs and blood samples obtained from patients longitudinally, with paired clinical data. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the longitudinal changes in driver landscape across a number of patients, in blood and buccum.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006800","title":"Characterization of a novel MEF2D-BCL9 fusion positive acute lymphoblastic leukemia cell line WXS","description":null,"abstract":"The lack of a well-characterized model system for many subtypes of leukemia hinders the development of targeted therapy and immunotherapy. A novel in-house-made pediatric MEF2D-BCL9 fusion positive acute lymphoblastic leukemia cell line was characterized. This cell line is highly presentative for the major clone of the original material and thus a valuable resource to examine novel therapeutic for MEF2D fused patients.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-28T12:37:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006801","title":"Characterization of a novel MEF2D-BCL9 fusion positive acute lymphoblastic leukemia cell line WXS derived","description":"The lack of a well-characterized model system for many subtypes of leukemia hinders the development of targeted therapy and immunotherapy. A novel in-house-made pediatric MEF2D-BCL9 fusion positive acute lymphoblastic leukemia cell line was characterized. This cell line is highly presentative for the major clone of the original material and thus a valuable resource to examine novel therapeutic for MEF2D fused patients.","abstract":"The lack of a well-characterized model system for many subtypes of leukemia hinders the development of targeted therapy and immunotherapy. A novel in-house-made pediatric MEF2D-BCL9 fusion positive acute lymphoblastic leukemia cell line was characterized. This cell line is highly presentative for the major clone of the original material and thus a valuable resource to examine novel therapeutic for MEF2D fused patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-28T12:57:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006802","title":"Characterization of a novel MEF2D-BCL9 fusion positive acute lymphoblastic leukemia cell line RNA-Seq","description":null,"abstract":"The lack of a well-characterized model system for many subtypes of leukemia hinders the development of targeted therapy and immunotherapy. A novel in-house-made pediatric MEF2D-BCL9 fusion positive acute lymphoblastic leukemia cell line was characterized. This cell line is highly presentative for the major clone of the original material and thus a valuable resource to examine novel therapeutic for MEF2D fused patients.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-28T13:02:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006803","title":"Characterization of a novel MEF2D-BCL9 fusion positive acute lymphoblastic leukemia cell line RNA-Seq derived","description":null,"abstract":"The lack of a well-characterized model system for many subtypes of leukemia hinders the development of targeted therapy and immunotherapy. A novel in-house-made pediatric MEF2D-BCL9 fusion positive acute lymphoblastic leukemia cell line was characterized. This cell line is highly presentative for the major clone of the original material and thus a valuable resource to examine novel therapeutic for MEF2D fused patients.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-28T13:10:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006804","title":"GOSH_Childhood_Tumours_Diseased_Behjati_CRUK_WGS","description":"Leukemia sample flow pilot.","abstract":"Leukemia sample flow pilot.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-29T10:37:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006805","title":"Highly sensitive liquid biopsy Duplex sequencing complements tissue biopsy to enhance detection of clinically relevant genetic variants","description":null,"abstract":"Background: Liquid biopsy (LB) is a promising complement to tissue biopsy for detection of clinically relevant genetic variants in cancer and mosaic diseases. A combined workflow to enable parallel tissue and LB analysis is required to maximize diagnostic yield for patients.\n\nMethods: We developed and validated a cost-efficient combined next-generation sequencing (NGS) workflow for both tissue and LB samples, and applied Duplex sequencing technology for highly accurate detection of low frequency variants in plasma. Clinically relevant cutoffs for variant reporting and quantification were established.\n\nResults: We investigated assay performance characteristics for very low amounts of clinically relevant variants. In plasma, the assay achieved 100% sensitivity and 92.3% positive predictive value (PPV) for single nucleotide variants (SNVs) and 91.7% sensitivity and 100% PPV for insertions and deletions (InDel) in clinically relevant hotspots with 0.5-5% variant allele frequencies (VAFs). We further established a cutoff for reporting variants (i.e. Limit of Blank, LOB) at 0.25% VAF and a cutoff for quantification (i.e. Limit of Quantification, LOQ) at 5% VAF in plasma for accurate clinical interpretation of analysis results. With our LB approach, we were able to identify the molecular cause of a clinically confirmed asymmetric overgrowth syndrome in a 10-year old child that would have remained undetected with tissue analysis as well as other molecular diagnostic approaches. \n\nConclusion: Our flexible and cost-efficient workflow allows analysis of both tissue and LB samples and provides clinically relevant cutoffs for variant reporting and precise quantification. Complementing tissue analysis by LB is likely to increase diagnostic yield for patients with molecular diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-29T11:40:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006806","title":"Targeted_NanoSeq__Spleen_","description":"Targeted NanoSeq in spleens from a number of healthy donors at the point of organ transplantation. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape in the spleen.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006807","title":"Detection of isoforms and genomic alterations by high-throughput full-length single-cell RNA sequencing in HGSOC","description":"Understanding the complex background of cancer requires genotype-phenotype information in single-cell resolution. Long-read single-cell RNA sequencing (scRNA-seq), capturing full-length transcripts, lacked the depth to provide this information so far. Here, we increased the PacBio sequencing depth to 12,000 reads per cell, leveraging multiple strategies, including artifact removal and transcript concatenation, and applied the technology to samples from three human ovarian cancer patients. Our approach captured 152,000 isoforms, of which over 52,000 were novel, detected cell type- and cell-specific isoform usage, and revealed differential isoform expression in tumor and mesothelial cells. Furthermore, we identified gene fusions, including a novel scDNA sequencing-validated IGF2BP2::TESPA1 fusion, which was misclassified as high TESPA1 expression in matched short-read data, and called somatic and germline mutations, confirming targeted NGS cancer gene panel results. With multiple new opportunities, especially for cancer biology, we envision long-read scRNA-seq to become increasingly relevant in oncology and personalized medicine.","abstract":"Understanding the complex background of cancer requires genotype-phenotype information in single-cell resolution. Long-read single-cell RNA sequencing (scRNA-seq), capturing full-length transcripts, lacked the depth to provide this information so far. Here, we increased the PacBio sequencing depth to 12,000 reads per cell, leveraging multiple strategies, including artifact removal and transcript concatenation, and applied the technology to samples from three human ovarian cancer patients. Our approach captured 152,000 isoforms, of which over 52,000 were novel, detected cell type- and cell-specific isoform usage, and revealed differential isoform expression in tumor and mesothelial cells. Furthermore, we identified gene fusions, including a novel scDNA sequencing-validated IGF2BP2::TESPA1 fusion, which was misclassified as high TESPA1 expression in matched short-read data, and called somatic and germline mutations, confirming targeted NGS cancer gene panel results. With multiple new opportunities, especially for cancer biology, we envision long-read scRNA-seq to become increasingly relevant in oncology and personalized medicine.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-29T14:21:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006808","title":"Loss of LGR4/GPR48 causes severe neonatal salt-wasting due to disrupted WNT signaling altering adrenal zonation","description":"Disorders of isolated mineralocorticoid deficiency causing potentially life-threatening salt-wasting crisis early in life have been associated with gene variants of aldosterone biosynthesis or resistance, but in some patients no such variants are found. WNT/β-catenin signaling is crucial for differentiation and maintenance of the aldosterone producing adrenal zona glomerulosa (zG). We describe a highly consanguineous family with multiple perinatal deaths or infants presenting at birth with failure to thrive, severe salt-wasting crises associated with isolated hypoaldosteronism, nail anomalies, short stature, and deafness. Whole exome sequencing revealed a homozygous splice variant in the R-SPONDIN receptor LGR4 gene (c.618-1G&gt;C) regulating WNT signaling. The resulting transcripts affected protein function and stability, and resulted in loss of Wnt/β-catenin signaling in vitro. The impact of LGR4 inactivation was analyzed by adrenal cortex specific ablation of Lgr4, using Lgr4Flox/Flox mated with Sf1:Cre mice. Inactivation of Lgr4 within the adrenal cortex in the mouse model caused decreased WNT signaling, aberrant zonation with deficient zG and reduced aldosterone production. Thus, human LGR4 mutations establish a direct link between LGR4 inactivation and decreased canonical WNT signaling with abnormal zG differentiation and endocrine function. Therefore, variants in WNT signaling and its regulators should systematically be considered in familial hyperreninemic hypoaldosteronism.","abstract":"Disorders of isolated mineralocorticoid deficiency causing potentially life-threatening salt-wasting crisis early in life have been associated with gene variants of aldosterone biosynthesis or resistance, but in some patients no such variants are found. WNT/β-catenin signaling is crucial for differentiation and maintenance of the aldosterone producing adrenal zona glomerulosa (zG). We describe a highly consanguineous family with multiple perinatal deaths or infants presenting at birth with failure to thrive, severe salt-wasting crises associated with isolated hypoaldosteronism, nail anomalies, short stature, and deafness. Whole exome sequencing revealed a homozygous splice variant in the R-SPONDIN receptor LGR4 gene (c.618-1G&gt;C) regulating WNT signaling. The resulting transcripts affected protein function and stability, and resulted in loss of Wnt/β-catenin signaling in vitro. The impact of LGR4 inactivation was analyzed by adrenal cortex specific ablation of Lgr4, using Lgr4Flox/Flox mated with Sf1:Cre mice. Inactivation of Lgr4 within the adrenal cortex in the mouse model caused decreased WNT signaling, aberrant zonation with deficient zG and reduced aldosterone production. Thus, human LGR4 mutations establish a direct link between LGR4 inactivation and decreased canonical WNT signaling with abnormal zG differentiation and endocrine function. Therefore, variants in WNT signaling and its regulators should systematically be considered in familial hyperreninemic hypoaldosteronism.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-29T15:39:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006809","title":"Study of Korean Parkinson's Disease","description":null,"abstract":"Single nucleotide variants (SNVs) associated with Parkinson’s disease (PD) have been investigated mainly through genome-wide association studies. Here, we conducted whole genome sequencing of 410 PD patients and 200 healthy individuals of the Korean population and identified disease-related SNVs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006810","title":"Quantitative and qualitative mutational impact of ionizing radiation on normal cells","description":"The comprehensive genomic impact of ionizing radiation (IR), a carcinogen, on healthy somatic cells remains unclear. Using large-scale whole-genome sequencing of clones expanded from irradiated murine and human single cells, we revealed that IR induces a characteristic spectrum of short nucleotide deletions and structural variations (SVs), including balanced inversions, translocations, composite SVs (deletion-insertion, deletion-inversion, and deletion-translocation composites), and complex genomic rearrangements (CGRs), including chromoplexy, chromothripsis, and SV by breakage-fusion-bridge cycles. Our findings suggest that 1 Gy of IR exposure causes an average of 2.33 mutational events per Gb genome, comprising 2.15 insertion-and-deletions, 0.17 SVs, and 0.01 CGRs, despite a high level of inter-cellular stochasticity. The mutational burden was dependent on total irradiation dose, regardless of dose rate and cell type. The findings were further validated in IR-induced secondary cancers and single cells without clonalization. Overall, our study highlights the comprehensive and clear picture of IR effects on normal mammalian genomes.","abstract":"The comprehensive genomic impact of ionizing radiation (IR), a carcinogen, on healthy somatic cells remains unclear. Using large-scale whole-genome sequencing of clones expanded from irradiated murine and human single cells, we revealed that IR induces a characteristic spectrum of short nucleotide deletions and structural variations (SVs), including balanced inversions, translocations, composite SVs (deletion-insertion, deletion-inversion, and deletion-translocation composites), and complex genomic rearrangements (CGRs), including chromoplexy, chromothripsis, and SV by breakage-fusion-bridge cycles. Our findings suggest that 1 Gy of IR exposure causes an average of 2.33 mutational events per Gb genome, comprising 2.15 insertion-and-deletions, 0.17 SVs, and 0.01 CGRs, despite a high level of inter-cellular stochasticity. The mutational burden was dependent on total irradiation dose, regardless of dose rate and cell type. The findings were further validated in IR-induced secondary cancers and single cells without clonalization. Overall, our study highlights the comprehensive and clear picture of IR effects on normal mammalian genomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006811","title":"Study of Korean Parkinson's disease","description":"Single nucleotide variants (SNVs) associated with Parkinson’s disease (PD) have been investigated mainly through genome-wide association studies. Here, we conducted whole genome sequencing of 410 PD patients and 200 healthy individuals of the Korean population and identified disease-related SNVs.","abstract":"Single nucleotide variants (SNVs) associated with Parkinson’s disease (PD) have been investigated mainly through genome-wide association studies. Here, we conducted whole genome sequencing of 410 PD patients and 200 healthy individuals of the Korean population and identified disease-related SNVs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-30T06:11:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006812","title":"Korean Parkinson's Disease Study","description":null,"abstract":"Single nucleotide variants (SNVs) associated with Parkinson’s disease (PD) have been investigated mainly through genome-wide association studies. Here, we conducted whole genome sequencing of 410 PD patients and 200 healthy individuals of the Korean population and identified disease-related SNVs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006813","title":"FFPE, buffycoat and cell free DNA from N. German esophagus cancer patients - 2021","description":"We recruited 28 patients and sequenced samples from their FFPE tissue, full blood buffy coat and plasma cell free DNA from diagnosis and other, longitudinal time points. The cell free DNA was sequenced ultra-deeply.  The IDT PanCancer panel was used for targeted enrichment. Aims: detection of primary tumor mutations in cell free DNA, overlap and difference in mutation profiles between primary tumor, metastases and cell free DNA.","abstract":"We recruited 28 patients and sequenced samples from their FFPE tissue, full blood buffy coat and plasma cell free DNA from diagnosis and other, longitudinal time points. The cell free DNA was sequenced ultra-deeply.  The IDT PanCancer panel was used for targeted enrichment. Aims: detection of primary tumor mutations in cell free DNA, overlap and difference in mutation profiles between primary tumor, metastases and cell free DNA.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-30T08:15:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006814","title":"Gene expression profiling of HGCC patient-derived Glioblastoma Cell Lines (ISPA-GBM)","description":null,"abstract":"Glioblastoma multiforme (GBM) is one of the most aggressive types of cancer and exhibits a profound genetic and epigenetic heterogeneity, making the development of an effective treatment a major challenge. The recent incorporation of molecular features into the diagnosis of GBM patients has led to an improved categorisation into different tumour subtypes with different prognosis and disease management. In this work, we have exploited the benefits of genome-wide multiomic approaches to identify potential molecular vulnerabilities existing on GBM patients. Integration of gene expression (this study) and DNA methylation data (arrayexpress entry E-MTAB-12473) from patient-derived GBM stem cell lines (pd-GBSCs) has revealed the presence of major sources of GBM variability, pinpointing subtype-specific tumour vulnerabilities amenable for pharmacological interventions. This dataset contains the transcriptional profiling (RNAseq) of 9 patient-derived Glioblastoma Cell Lines obtained from the HGCC resource and 4 non-tumoral brains from the Hospital Universitario Central de Asturias (ISPA-HUCA).","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006815","title":"DERMATLAS__Hidradenocarcinoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Hidradenocarcinoma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Hidradenocarcinoma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006816","title":"DERMATLAS__Proliferating_pilar_tumour_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are proliferating pilar tumours.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are squamoid proliferating pilar tumours.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006817","title":"RNAseq PDX samples from patients AML007 and AML013","description":null,"abstract":"Comparison for PDX subjected to different treatment: AraC, Bay, Combo (AraC+Bay)","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006818","title":"The impact of BNT162b2 mRNA vaccine against SARS-CoV-2 on adaptive and innate immune responses","description":"The mRNA-based BNT162b2 protects against severe disease and mortality caused by SARS-CoV-2 through induction of specific antibody and T-cell responses. Much less is known about its broad effects on immune responses against other pathogens. In the present study, we investigated the specific adaptive immune responses induced by BNT162b2 vaccination against various SARS-CoV-2 variants, as well as its effects on the responsiveness of human immune cells upon stimulation with heterologous viral, bacterial, and fungal pathogens. BNT162b2 vaccination induced effective humoral and cellular immunity against SARS-CoV-2 that started to wane after six months. We also observed long-term transcriptional changes in immune cells after vaccination, as assessed by RNA sequencing. Additionally, vaccination with BNT162b2 modulated innate immune responses as measured by the production of inflammatory cytokines when stimulated with various microbial stimuli other than SARS-CoV-2, including higher IL-1/IL-6 release and decreased production of IFN-α. Altogether, these data expand our knowledge regarding the overall immunological effects of this new class of vaccines and underline the need of additional studies to elucidate their effects on both innate and adaptive immune responses.","abstract":"The mRNA-based BNT162b2 protects against severe disease and mortality caused by SARS-CoV-2 through induction of specific antibody and T-cell responses. Much less is known about its broad effects on immune responses against other pathogens. In the present study, we investigated the specific adaptive immune responses induced by BNT162b2 vaccination against various SARS-CoV-2 variants, as well as its effects on the responsiveness of human immune cells upon stimulation with heterologous viral, bacterial, and fungal pathogens. BNT162b2 vaccination induced effective humoral and cellular immunity against SARS-CoV-2 that started to wane after six months. We also observed long-term transcriptional changes in immune cells after vaccination, as assessed by RNA sequencing. Additionally, vaccination with BNT162b2 modulated innate immune responses as measured by the production of inflammatory cytokines when stimulated with various microbial stimuli other than SARS-CoV-2, including higher IL-1/IL-6 release and decreased production of IFN-α. Altogether, these data expand our knowledge regarding the overall immunological effects of this new class of vaccines and underline the need of additional studies to elucidate their effects on both innate and adaptive immune responses.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-30T10:54:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006819","title":"Erythroid/megakaryocytic differentiation confers BCL-XL dependency and venetoclax resistance in acute myeloid leukemia","description":"Myeloid neoplasms with erythroid or megakaryocytic differentiation include pure erythroid leukemia (PEL), myelodysplastic syndrome (MDS) with erythroid features, and acute megakaryoblastic leukemia (FAB M7) and are characterized by poor prognosis and limited treatment options. Here, we investigate the drug sensitivity landscape of these rare malignancies. We show that acute myeloid leukemia (AML) cells with erythroid or megakaryocytic differentiation depend on the anti-apoptotic protein BCL-XL, rather than BCL-2, using combined ex vivo drug sensitivity testing, genetic perturbation, and transcriptomic profiling. Single-cell and bulk transcriptomics of patient samples with erythroid and megakaryoblastic leukemias identified high BCL2L1 expression compared to other subtypes of AML and other hematological malignancies, where BCL2 and MCL1 were more prominent. Our results suggest targeting BCL-XL as a potential therapy option in erythroid/megakaryoblastic leukemias and highlight an AML subgroup with potentially reduced sensitivity to venetoclax-based treatments.","abstract":"Myeloid neoplasms with erythroid or megakaryocytic differentiation include pure erythroid leukemia (PEL), myelodysplastic syndrome (MDS) with erythroid features, and acute megakaryoblastic leukemia (FAB M7) and are characterized by poor prognosis and limited treatment options. Here, we investigate the drug sensitivity landscape of these rare malignancies. We show that acute myeloid leukemia (AML) cells with erythroid or megakaryocytic differentiation depend on the anti-apoptotic protein BCL-XL, rather than BCL-2, using combined ex vivo drug sensitivity testing, genetic perturbation, and transcriptomic profiling. Single-cell and bulk transcriptomics of patient samples with erythroid and megakaryoblastic leukemias identified high BCL2L1 expression compared to other subtypes of AML and other hematological malignancies, where BCL2 and MCL1 were more prominent. Our results suggest targeting BCL-XL as a potential therapy option in erythroid/megakaryoblastic leukemias and highlight an AML subgroup with potentially reduced sensitivity to venetoclax-based treatments.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-30T13:19:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006820","title":"NPY methylated ctDNA is a promising biomarker for treatment response monitoring in metastatic colorectal cancer","description":null,"abstract":"Abstract\nPurpose \nAnalysis of methylation markers in liquid biopsies is a promising technique for the follow-up of metastatic colorectal cancer (mCRC) patients, since they can be used in all patients, regardless of their mutational status. Therefore, we studied the value of NPY methylation analysis in circulating tumor DNA (ctDNA) for accurate response monitoring in mCRC patients in the PANIB trial.\nExperimental design\nThe PANIB trial was a randomized phase two trial designed to compare FOLFOX plus panitumumab and FOLFOX plus bevacizumab in patients with RAS wild-type unresectable mCRC. The results of sequential liquid biopsies were correlated with results of imaging.\nResults\nForty patients were included from six Belgian hospitals. Analysis of the liquid biopsies revealed that higher baseline levels of methylated ctDNA was associated with a significantly shorter overall survival (HR, 1.015; 95% CI 1.005 -1.025 and p=0.002). Furthermore, thirty-seven patients provided at least two liquid biopsies. Thirty-one of them showed a decrease in the methylation ratio after the start of therapy, which corresponded with stable disease or response on imaging at the first evaluation.\nWhen comparing the panitumumab and bevacizumab arm, significantly higher objective response and early tumor shrinkage rates were observed in the panitumumab arm (p=0.048 and p=0.015, respectively). However, due to a small study population, the trial was underpowered to detect a significant difference in survival. \nConclusions\nThe results of this study confirm that baseline methylated ctDNA is a prognostic marker and indicate that NPY methylation is a promising marker for response monitoring in patients with mCRC","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-11-30T16:17:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006821","title":"Tumor educated platelets for BrCA","description":null,"abstract":"We developed classifiers for the detection of (early) breast cancer based on tumor educated platelets (TEPs).","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-01T07:32:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006822","title":"TCR targeting FLT3 D835Y mutation","description":"We identified a T-cell receptor (TCR) reactive to the recurrent FLT3 D835Y mutation in the tyrosine-kinase domain. To validate the elimination efficacy of leukemia cells, we transplanted human acute myeloid leukemia (AML) cells with FLT3 D835Y mutations into NSG-SGM3 mice and treated either with TCR FLT3 D835Y redirected T cells, or control TCR (TCR 1G4). After treatment, we performed flow sorting of AML blasts (CD3-CD19-) and primary T cells (CD3+CD8+orCD4+CD19-CD33-) and performed whole-exome sequencing.","abstract":"We identified a T-cell receptor (TCR) reactive to the recurrent FLT3 D835Y mutation in the tyrosine-kinase domain. To validate the elimination efficacy of leukemia cells, we transplanted human acute myeloid leukemia (AML) cells with FLT3 D835Y mutations into NSG-SGM3 mice and treated either with TCR FLT3 D835Y redirected T cells, or control TCR (TCR 1G4). After treatment, we performed flow sorting of AML blasts (CD3-CD19-) and primary T cells (CD3+CD8+orCD4+CD19-CD33-) and performed whole-exome sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006823","title":"Profiling of childhood neuroblastoma and the immune microenvironment by single-cell sequencing of RNA and TCR","description":"Neuroblastoma tumor cells and their tumor microenvironment are studied by single-cell RNA sequencing of primary neuroblastoma tumors and neuroblastoma-infiltrated tissues/metastases. Both diagnostic samples, taken pre-treatment and samples taken after induction chemotherapy at surgical resection and biopsies from relapse samples are included.  For a number of patients single-cell RNA sequencing of blood samples (controls) are included and additionally we  performed single-cell T cell receptor sequencing (TCR) on the tumor and blood samples. With this study, we will focus on identifying differences in tumor cells and their (immune) microenvironment 1) before and after treatment or at relapse and 2) between primary tumors and infiltrated tissues/metastases. Moreover, with TCR sequencing we aim to unveil immune cell dynamics in patients with neuroblastoma.","abstract":"Neuroblastoma tumor cells and their tumor microenvironment are studied by single-cell RNA sequencing of primary neuroblastoma tumors and neuroblastoma-infiltrated tissues/metastases. Both diagnostic samples, taken pre-treatment and samples taken after induction chemotherapy at surgical resection and biopsies from relapse samples are included.  For a number of patients single-cell RNA sequencing of blood samples (controls) are included and additionally we  performed single-cell T cell receptor sequencing (TCR) on the tumor and blood samples. With this study, we will focus on identifying differences in tumor cells and their (immune) microenvironment 1) before and after treatment or at relapse and 2) between primary tumors and infiltrated tissues/metastases. Moreover, with TCR sequencing we aim to unveil immune cell dynamics in patients with neuroblastoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-01T09:17:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006824","title":"Transcriptional_Landscape_in_Healthy_Breast","description":"LCM RNAseq of healthy breast tissue","abstract":"Investigating impact of driver events on transcriptome in healthy breast.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006825","title":"Aplastic_anaemia_colonies_WGS","description":"Aplastic anaemia blood colony WGS","abstract":"Aplastic anaemia blood colony WGS","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006826","title":"Epigenome-wide association study of cocaine use disorder in postmortem human brain tissue","description":"We aimed to identify cocaine use disorder associated DNA methylation alterations in the Brodmann Area 9 brain region.","abstract":"We aimed to identify cocaine use disorder associated DNA methylation alterations in the Brodmann Area 9 brain region.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-01T11:17:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006827","title":"Aplastic_anaemia_bulk_Nanoseq","description":"Aplastic anaemia blood Nanoseq","abstract":"Aplastic anaemia blood Nanoseq","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006828","title":"Schwachmann_Diamond_Nanoseq","description":"SDS blood Nanoseq","abstract":"SDS blood Nanoseq","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006829","title":"Chronic_myeloid_leukaemia_Nanoseq","description":"CML blast crisis Nanoseq","abstract":"CML blast crisis Nanoseq","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006830","title":"Circulating DNA reveals a specific higher fragmentation of Y chromosome","description":null,"abstract":"Chromosomal variability of DNA degradation in blood remains largely unknown. Here we show that (i) the size profiles of total circulating DNA (cirDNA) and DNA fragments originated from autosomes and chromosome X in blood plasma are homogeneous and have remarkably low variability among healthy individuals, (ii) Y chromosome Y has a distinct fragment cirDNA size profile in blood and its fragment fraction in blood decreases with age. These results indicate a higher fragmentation of the Y chromosome and an increased susceptibility to degradation compared to other chromosomes.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006831","title":"Dynamics of sequence and structural cell-free DNA landscapes in small-cell lung cancer","description":"Patients with small-cell lung cancer (SCLC) have an exceptionally poor prognosis, calling for improved real-time non-invasive biomarkers of therapeutic response. We performed targeted error-correction sequencing on 171 serial plasmas and matched white blood cell (WBC) DNA from 33 patients with metastatic SCLC who received systemic treatment with chemotherapy or immunotherapy-containing regimens. Tumor-derived sequence alterations and plasma aneuploidy were evaluated serially and combined to assess changes in total cell-free tumor load (cfTL). Longitudinal dynamic changes in cfTL were monitored to determine circulating cell-free tumor DNA (ctDNA) molecular response during therapy. Combined tiered analyses of tumor-derived sequence alterations and plasma aneuploidy allowed for assessment of ctDNA molecular response in all patients. Molecular responses captured the therapeutic effect and long-term clinical outcomes in a more accurate and rapid manner compared to radiographic imaging. Patients with sustained molecular responses had longer overall (log-rank p=0.0006) and progression-free (log-rank p&lt;0.0001) survival, with molecular responses detected on average 4 weeks earlier than imaging. ctDNA analyses provide a rapid approach for the assessment of early on-therapy molecular responses and have important implications for the management of patients with SCLC, including the development of improved strategies for real-time tumor burden monitoring.","abstract":"Patients with small-cell lung cancer (SCLC) have an exceptionally poor prognosis, calling for improved real-time non-invasive biomarkers of therapeutic response. We performed targeted error-correction sequencing on 171 serial plasmas and matched white blood cell (WBC) DNA from 33 patients with metastatic SCLC who received systemic treatment with chemotherapy or immunotherapy-containing regimens. Tumor-derived sequence alterations and plasma aneuploidy were evaluated serially and combined to assess changes in total cell-free tumor load (cfTL). Longitudinal dynamic changes in cfTL were monitored to determine circulating cell-free tumor DNA (ctDNA) molecular response during therapy. Combined tiered analyses of tumor-derived sequence alterations and plasma aneuploidy allowed for assessment of ctDNA molecular response in all patients. Molecular responses captured the therapeutic effect and long-term clinical outcomes in a more accurate and rapid manner compared to radiographic imaging. Patients with sustained molecular responses had longer overall (log-rank p=0.0006) and progression-free (log-rank p&lt;0.0001) survival, with molecular responses detected on average 4 weeks earlier than imaging. ctDNA analyses provide a rapid approach for the assessment of early on-therapy molecular responses and have important implications for the management of patients with SCLC, including the development of improved strategies for real-time tumor burden monitoring.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-01T17:20:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006832","title":"The role of MALT1 in driving IBN resistance in MCL","description":"The bulk RNA-seq dataset was generated for the cell lines below and used for two major purposes:\n1.\tDEG analysis and GSEA analysis comparing IBN-R and IBN-S cells\n2.\tDEG analysis and GSEA analysis comparing MCL cells with/without MI-2 treatment.","abstract":"The bulk RNA-seq dataset was generated for the cell lines below and used for two major purposes:\n1.\tDEG analysis and GSEA analysis comparing IBN-R and IBN-S cells\n2.\tDEG analysis and GSEA analysis comparing MCL cells with/without MI-2 treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-01T22:32:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006833","title":"Malignant progression of an ancestral bone marrow clone harboring a CIC-NUTM2A fusion in isolated myeloid sarcoma","description":"Myeloid sarcoma is a rare condition consisting of extramedullary myeloid blasts found in association with acute myeloid leukemia (AML) or, in the absence of bone marrow involvement. We identified an infant with isolated myeloid sarcoma whose bone marrow was negative for involvement by flow cytometry. Sequencing revealed the fusion oncogene CIC-NUTM2A and identified the sarcoma to be clonally evolved from the bone marrow which carried the fusion despite the absence of pathology. Murine modeling confirmed the ability of the fusion to transform hematopoietic cells and identified receptor tyrosine kinase signaling activation consistent with disruption of the CIC transcriptional repressor. These findings extend the definition of CIC-rearranged malignancies to include hematologic disease, provide insight into the mechanism of oncogenesis, and demonstrate the importance of molecular analysis and tracking of bone marrow involvement over the course of treatment in myeloid sarcoma, including patients that lack flow cytometric evidence of leukemia at diagnosis.","abstract":"Myeloid sarcoma is a rare condition consisting of extramedullary myeloid blasts found in association with acute myeloid leukemia (AML) or, in the absence of bone marrow involvement. We identified an infant with isolated myeloid sarcoma whose bone marrow was negative for involvement by flow cytometry. Sequencing revealed the fusion oncogene CIC-NUTM2A and identified the sarcoma to be clonally evolved from the bone marrow which carried the fusion despite the absence of pathology. Murine modeling confirmed the ability of the fusion to transform hematopoietic cells and identified receptor tyrosine kinase signaling activation consistent with disruption of the CIC transcriptional repressor. These findings extend the definition of CIC-rearranged malignancies to include hematologic disease, provide insight into the mechanism of oncogenesis, and demonstrate the importance of molecular analysis and tracking of bone marrow involvement over the course of treatment in myeloid sarcoma, including patients that lack flow cytometric evidence of leukemia at diagnosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-02T04:25:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006834","title":"Y90 radioembolization followed by intravenous Nivolumab for advanced hepatocellular carcinoma","description":"To evaluate the efficacy of combination therapy with ICI and RT in patients, a Phase II trial (CA209-678) was conducted to investigate the efficacy and safety of Y90-RE followed by nivolumab in patients with advanced HCC (NCT03033446, n = 36). Interestingly, the ORR was found to be 30.6% in all patients and 43.5% when restricted to patients with only intrahepatic tumors, suggesting possible synergism between Y90-RE and ICI. Here we present whole exome sequencing (WES) and RNA-seq data for 33 patients treated with Y90 radioembolization followed with Nivolumab.","abstract":"To evaluate the efficacy of combination therapy with ICI and RT in patients, a Phase II trial (CA209-678) was conducted to investigate the efficacy and safety of Y90-RE followed by nivolumab in patients with advanced HCC (NCT03033446, n = 36). Interestingly, the ORR was found to be 30.6% in all patients and 43.5% when restricted to patients with only intrahepatic tumors, suggesting possible synergism between Y90-RE and ICI. Here we present whole exome sequencing (WES) and RNA-seq data for 33 patients treated with Y90 radioembolization followed with Nivolumab.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-02T08:25:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006835","title":"Overlapping features of therapy-related and de novo NPM1-mutated AML","description":null,"abstract":"NPM1-mutated AML represents a WHO leukemia entity with unique pathological and clinical features. Little is known about the characteristics of “therapy-related” NPM1-mutated AML.\n\nWe compared the genetics, transcriptional profile and clinical outcome of therapy-related NPM1-mutated AML (t-NPM1 AML), de-novo NPM1-mutated AML (dn-NPM1 AML) and therapy-related AML with wild-type NPM1 (t-AML). A normal karyotype was more frequent in t-NPM1 AML (n=78/96 cases, 88%) and dn-NPM1 (n=1986/2394,88%) than in t-AML (n=103/390,28%; p &lt;0.001). DNMT3A and TET2 were mutated in 43% and 40% of t-NPM1 AML (n=107), similar to dn-NPM1 (n=88, 48% and 30%; p-values &gt;0.1), but more frequently than t-AML (n=162; 14% and 10%; p-values &lt;0.001). TP53 and PPM1D, typically mutated in t-AML, were consistently wild-type in t-NPM1 AML (97% and 96%). t-NPM1 and dn-NPM1 AML were transcriptionally similar, displaying upregulation of HOX genes and down-regulation of CD133 and CD34. With a median follow-up of 62 months, 3-year overall survival (OS) for t-NPM1 AML (n=96), dn-NPM1 AML (n=2394) and t-AML (n=390) was 54%, 60% and 31%. In multivariable analysis OS was similar for the two NPM1-mutated groups (HR 0.9, 95%CI 0.65–1.25, p=0.45) but better in t-NPM1 AML than t-AML (HR 1.86, 95%CI 1.30–2.68, p&lt;0.001). Relapse-free survival did not differ between t-NPM1 and dn-NPM1 AML (HR 1.02, 95%CI 0.72-1.467, p=0.90) but was significantly higher in t-NPM1 AML than t-AML (HR 1.77, 95%CI 1.19-2.64, p=0.0045).t-NPM1 and dn-NPM1 AML have similar clinical, genomic and transcriptomic features, suggesting that they should be classified as a single disease entity","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006836","title":"Single cell RNA sequencing of bone marrow mononuclear cells","description":"Bone marrow aspirates were obtained from patients with relapsed/refractory large B cell lymphoma (rrLBCL), mononuclear cells isolated by ficoll density-gradient centrifugation, and loaded onto a 10X Chromium for single cell RNA-sequencing using 5’ chemistry without prior cryopreservation. Healthy donor bone marrow mononuclear cells were obtained from healthy allogeneic stem cell transplant donors and analyzed following viable cryopreservation.","abstract":"Bone marrow aspirates were obtained from patients with relapsed/refractory large B cell lymphoma (rrLBCL), mononuclear cells isolated by ficoll density-gradient centrifugation, and loaded onto a 10X Chromium for single cell RNA-sequencing using 5’ chemistry without prior cryopreservation. Healthy donor bone marrow mononuclear cells were obtained from healthy allogeneic stem cell transplant donors and analyzed following viable cryopreservation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-02T14:10:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006837","title":"Orphan_Tumour_Study_NB_sNuc_WGS","description":"The aim of this study is to investigate the genomic landscape of human cancer.","abstract":"The aim of this study is to investigate the genomic landscape of human cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-02T14:27:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006838","title":"Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial","description":"The IMagyn050 trial (NCT03038100), which evaluated the efficacy of Atezo vs placebo (Pla) with carboplatin, paclitaxel and bevacizumab (CPB) in front line ovarian cancer patient (pts), did not meet its co-primary endpoints of PFS in ITT or PD-L1+ (Moore et al. JCO 2021). The aim of this exploratory study was to evaluate whether patients with BRCA1/2-mutated or homologous recombination-deficient (HRD) ovarian cancers benefitted from atezolizumab in the phase III IMagyn050 (NCT03038100) trial. Methods: Patients with newly diagnosed ovarian cancer were randomized to either atezolizumab or placebo with standard chemotherapy and bevacizumab. PD-L1 status of tumor-infiltrating immune cells was determined centrally (VENTANA SP142 assay). Genomic alterations, including deleterious BRCA1/2 alterations, genomic loss of heterozygosity (gLOH), tumor mutation burden (TMB), and microsatellite instability (MSI), were evaluated using the FoundationOne assay. HRD was defined as gLOH ≥16%, regardless of BRCA1/2 mutation status. Potential associations between progression-free survival (PFS) and genomic biomarkers were evaluated using standard correlation analyses and log-rank of Kaplan-Meier estimates. Results Among biomarker-evaluable samples, 22% (234/1050) harbored BRCA1/2 mutations and 46% (446/980) were HRD. Median TMB was low irrespective of BRCA1/2 or HRD. Only 3% (29/1024) had TMB ≥10 mut/Mb and 0.3% (3/1022) were MSI-high. PFS was better in BRCA2-mutated versus BRCA2-non-mutated tumors and in HRD versus proficient tumors. PD-L1 positivity (≥1% expression on immune cells) was associated with HRD but not BRCA1/2 mutations. PFS was not improved by adding atezolizumab in BRCA2-mutated or HRD tumors; there was a trend toward enhanced PFS with atezolizumab in BRCA1-mutated tumors. Conclusion Most ovarian tumors have low TMB despite BRCA1/2 mutations or HRD. Neither BRCA1/2 mutation nor HRD predicted enhanced benefit from atezolizumab. This is the first randomized double-blind trial in ovarian cancer demonstrating that genomic instability triggered by BRCA1/2 mutation or HRD is not associated with improved sensitivity to immune checkpoint inhibitors.","abstract":"The IMagyn050 trial (NCT03038100), which evaluated the efficacy of Atezo vs placebo (Pla) with carboplatin, paclitaxel and bevacizumab (CPB) in front line ovarian cancer patient (pts), did not meet its co-primary endpoints of PFS in ITT or PD-L1+ (Moore et al. JCO 2021). The aim of this exploratory study was to evaluate whether patients with BRCA1/2-mutated or homologous recombination-deficient (HRD) ovarian cancers benefitted from atezolizumab in the phase III IMagyn050 (NCT03038100) trial. Methods: Patients with newly diagnosed ovarian cancer were randomized to either atezolizumab or placebo with standard chemotherapy and bevacizumab. PD-L1 status of tumor-infiltrating immune cells was determined centrally (VENTANA SP142 assay). Genomic alterations, including deleterious BRCA1/2 alterations, genomic loss of heterozygosity (gLOH), tumor mutation burden (TMB), and microsatellite instability (MSI), were evaluated using the FoundationOne assay. HRD was defined as gLOH ≥16%, regardless of BRCA1/2 mutation status. Potential associations between progression-free survival (PFS) and genomic biomarkers were evaluated using standard correlation analyses and log-rank of Kaplan-Meier estimates. Results Among biomarker-evaluable samples, 22% (234/1050) harbored BRCA1/2 mutations and 46% (446/980) were HRD. Median TMB was low irrespective of BRCA1/2 or HRD. Only 3% (29/1024) had TMB ≥10 mut/Mb and 0.3% (3/1022) were MSI-high. PFS was better in BRCA2-mutated versus BRCA2-non-mutated tumors and in HRD versus proficient tumors. PD-L1 positivity (≥1% expression on immune cells) was associated with HRD but not BRCA1/2 mutations. PFS was not improved by adding atezolizumab in BRCA2-mutated or HRD tumors; there was a trend toward enhanced PFS with atezolizumab in BRCA1-mutated tumors. Conclusion Most ovarian tumors have low TMB despite BRCA1/2 mutations or HRD. Neither BRCA1/2 mutation nor HRD predicted enhanced benefit from atezolizumab. This is the first randomized double-blind trial in ovarian cancer demonstrating that genomic instability triggered by BRCA1/2 mutation or HRD is not associated with improved sensitivity to immune checkpoint inhibitors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-02T22:09:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006839","title":"Detection of rare mutations, copy number variation, and DNA methylation in the same template DNA molecules","description":"The analysis of cell-free DNA (cfDNA) from plasma offers great promise for the earlier detection of cancer. At present, changes in DNA sequence, methylation, or copy number are the most sensitive ways to detect the presence of cancer. To further increase the sensitivity of such assays with limited amounts of sample, it would be useful to be able to evaluate the same template molecules for all these changes. Here we report an approach, called MethylSaferSeqS, that achieves this goal, and can be applied to any standard library preparation method suitable for massively parallel sequencing. The innovative step was to copy both strands of each DNA-barcoded molecule with a primer that allows the subsequent separation of the original strands (retaining their 5-methylcytosine residues) from the copied strands (in which the 5-methylcytosine residues are replaced with unmodified cytosine residues). The epigenetic and genetic alterations present in the DNA molecules can then be obtained from the original and copied strands, respectively. We applied this approach to plasma from 265 individuals, including 198 with cancers of the pancreas, ovary, lung and colon, and found the expected patterns of mutations, copy number alterations, and methylation. Furthermore, we could determine which original template DNA molecules were methylated and/or mutated. MethylSaferSeqS should be useful for addressing a variety of questions relating genetics and epigenetics in the future.","abstract":"The analysis of cell-free DNA (cfDNA) from plasma offers great promise for the earlier detection of cancer. At present, changes in DNA sequence, methylation, or copy number are the most sensitive ways to detect the presence of cancer. To further increase the sensitivity of such assays with limited amounts of sample, it would be useful to be able to evaluate the same template molecules for all these changes. Here we report an approach, called MethylSaferSeqS, that achieves this goal, and can be applied to any standard library preparation method suitable for massively parallel sequencing. The innovative step was to copy both strands of each DNA-barcoded molecule with a primer that allows the subsequent separation of the original strands (retaining their 5-methylcytosine residues) from the copied strands (in which the 5-methylcytosine residues are replaced with unmodified cytosine residues). The epigenetic and genetic alterations present in the DNA molecules can then be obtained from the original and copied strands, respectively. We applied this approach to plasma from 265 individuals, including 198 with cancers of the pancreas, ovary, lung and colon, and found the expected patterns of mutations, copy number alterations, and methylation. Furthermore, we could determine which original template DNA molecules were methylated and/or mutated. MethylSaferSeqS should be useful for addressing a variety of questions relating genetics and epigenetics in the future.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006840","title":"Multimodal_Single_cell_Assessment_of_T_cell_Proliferation_Trajectory","description":"In this project, we aim to perform multimodal assessment of primary T-cells to establish the genetic and epigenetic underpinnings of T-cell proliferation. We aim to pursue understanding of T-cell proliferation on a transcriptomic, proteomic and epigenetic level.","abstract":"Immune-mediated diseases result from complex aetiologies, largely summarised as dysregulation in the complex interactions between genetic variation and the environment. The spectrum of immunopathologies share underlying mechanisms (see Review: Wu et al., 2015).\nVarious studies have associated CD4+ T-cells in immune-mediated disease – using statistical fine mapping (Farh et al., 2015), changes in chromatin accessibility (Soskic et al. 2018) and classical immunological studies (Review: Skapenko et al., 2005). \nFundamental to T-cell activity is proliferation. Following activation of the T-cell receptor and co-stimulation from CD28, Naïve and Memory T-cells will proliferate through clonal expansion. \nInterestingly, non-specific stimulation from anti-CD3 and anti-CD28 results in distinct peaks of proliferation, indicating a non-uniform response to stimulation. The heterogeneity in response to stimulation has been studied in CD8+ T-cells (Plambeck et al., 2022, Marchingo et al., 2016), however CD4+ proliferation remains a largely unreported topic. \nPrevious studies in the Trynka lab have performed transcriptional mapping of CD4+ T-cells following stimulation (Soskic et al., 2022), in which a subpopulation of lowly-activated T-cells were identified. This poses question of the spectrum of activation following stimulation and the resulting influence on proliferation. \nThis study will provide a valuable insight into understanding the heterogeneity in T-cell proliferation. The dataset provides potential for independent insights, whilst bridging previous datasets generated in the Trynka lab (Soskic et al., 2022, Soskic  et al., 2018). Given the recognised role of T-cells in the aetiology of immune-mediated pathologies, this study has potential to gain deeper understanding of the genetic underpinnings of disease.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006841","title":"Subcutaneous adipose tissues of NAFLD patients","description":null,"abstract":"Adipocyte hypertrophy and expression of adipokines in subcutaneous adipose tissue (SAT) have been linked to steatosis, nonalcoholic steatohepatitis (NASH) and fibrosis in morbidly obese (BMI ≥ 40 kg/ m2) subjects. It is unknown if this is also true for subjects with NAFLD with lesser degrees of obesity (BMI &amp;lt; 35 kg/m2). Thirty-two subjects with biopsy-proven NAFLD and 15 non-diabetic controls matched for BMI underwent fine-needle biopsies of SAT. Adipocyte volume was calculated. RNA- sequencing of SAT was performed in a subset of 20 NAFLD patients. Adipocyte volume and gene expression levels were correlated to the presence of NASH or significant fibrosis. Subjects with NAFLD had larger adipocyte volume compared with controls, (1939 pL, 95% CI 1130–1662 vs. 854 pL, 95% CI 781–926, p &amp;lt; 0.001). There was no association between adipocyte volume and the presence of NASH. Gene expression of adipokines previously described to correlate with NASH in morbid obesity, was\nnot associated with NASH or fibrosis. Our results suggest that persons with NAFLD have larger SAT adipocytes compared with controls and that adipocytes are involved in the pathophysiology of hepatic steatosis in NAFLD. However, adipocyte volume was not associated with NASH or fibrosis in NAFLD subjects with varying degrees of obesity.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006842","title":"Liver NPCs single cell project","description":"Independent of their inflammatory phenotype, macrophages are key orchestrators of hepatic metabolism. Non-alcoholic fatty liver disease (NAFLD), often observed in obese individuals, is among the most common causes of cirrhosis, the end-stage of chronic liver disease that may necessitates liver transplantation. While multiple populations of macrophages have been described in the human liver, their function and turnover in obese patients, who are at high risk of developing NAFLD and cirrhosis, is currently unknown. Herein we identified a specific human population of resident liver macrophages that protects against the metabolic impairment associated with obesity. Strikingly, by studying the dynamics of liver macrophages in individuals undergoing liver transplantation using markers of donor-recipient mismatch, we discovered that liver macrophage turnover differs dramatically in humans and in mice. Using single cell techniques, flow cytometry and functional validation approaches in human 3D cultures, we discovered that the proportion of the protective resident liver macrophages decreases during obesity. Considering the failure of drugs blocking monocyte infiltration to blunt liver fibrosis in clinical trials, our study indicates that resident macrophages could be a better therapeutic target to combat NAFLD progression into life-threatening liver diseases.","abstract":"Independent of their inflammatory phenotype, macrophages are key orchestrators of hepatic metabolism. Non-alcoholic fatty liver disease (NAFLD), often observed in obese individuals, is among the most common causes of cirrhosis, the end-stage of chronic liver disease that may necessitates liver transplantation. While multiple populations of macrophages have been described in the human liver, their function and turnover in obese patients, who are at high risk of developing NAFLD and cirrhosis, is currently unknown. Herein we identified a specific human population of resident liver macrophages that protects against the metabolic impairment associated with obesity. Strikingly, by studying the dynamics of liver macrophages in individuals undergoing liver transplantation using markers of donor-recipient mismatch, we discovered that liver macrophage turnover differs dramatically in humans and in mice. Using single cell techniques, flow cytometry and functional validation approaches in human 3D cultures, we discovered that the proportion of the protective resident liver macrophages decreases during obesity. Considering the failure of drugs blocking monocyte infiltration to blunt liver fibrosis in clinical trials, our study indicates that resident macrophages could be a better therapeutic target to combat NAFLD progression into life-threatening liver diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006843","title":"TK-EPN862 - Patient-dervied xenograft model of Posterior Fossa A Ependymoma - WGS","description":null,"abstract":"Ependymomas (EPN) are the third most common malignant brain cancer in children. Treatment strategies for pediatric EPN have remained unchanged over recent decades, with 10-year survival rates stagnating at just 67% for children aged 0-14 years. Moreover, patients who survive treatment for the most common subtype of pediatric EPN (posterior fossa A (PFA)), often suffer long-term neurological side effects as a result of therapy. It is evident that there is a need for safer, more effective treatments for pediatric EPN patients. There are ten distinct subgroups of EPN, each with their own molecular and prognostic features. To identify and facilitate the testing of new treatments for EPN, in vivo laboratory models representative of the diverse molecular subtypes are required. Here, we describe the establishment of a patient-derived orthotopic xenograft (PDOX) model of PFA EPN, derived from a metastatic cranial lesion. Patient and PDOX tumors were analyzed using immunohistochemistry, DNA methylation profiling, whole genome sequencing (WGS) and RNA sequencing. Both patient and PDOX tumors classified as PFA EPN by methylation profiling, and shared similar histological features consistent with this molecular subgroup. RNA sequencing revealed that gene expression patterns were maintained across the primary and metastatic tumors, as well as the PDOX. Copy number profiling revealed gains of chromosomes 7, 8 and 19, and loss of chromosomes 2q and 6q in the PDOX and matched patient tumor. No clinically significant single nucleotide variants were identified, consistent with the low mutation rates observed in PFA EPN. Overexpression of EZHIP RNA and protein, a common feature of PFA EPN, was also observed. Despite the aggressive nature of the tumor in the patient, this PDOX was unable to be maintained past two passages in vivo. Others who have successfully developed PDOX models report some of the lowest success rates for EPN compared to other pediatric brain cancer types attempted, with loss of tumorigenicity not uncommon, highlighting the challenge in propagating these tumors in the laboratory. Here, we discuss our collective experiences with PFA EPN PDOX model generation and propose potential approaches to improve future success in establishing preclinical EPN models.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-06T04:34:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006844","title":"TK-EPN862 - Patient-dervied xenograft model of Posterior Fossa A Ependymoma - RNAseq","description":"Ependymomas (EPN) are the third most common malignant brain cancer in children. Treatment strategies for pediatric EPN have remained unchanged over recent decades, with 10-year survival rates stagnating at just 67% for children aged 0-14 years. Moreover, patients who survive treatment for the most common subtype of pediatric EPN (posterior fossa A (PFA)), often suffer long-term neurological side effects as a result of therapy. It is evident that there is a need for safer, more effective treatments for pediatric EPN patients. There are ten distinct subgroups of EPN, each with their own molecular and prognostic features. To identify and facilitate the testing of new treatments for EPN, in vivo laboratory models representative of the diverse molecular subtypes are required. Here, we describe the establishment of a patient-derived orthotopic xenograft (PDOX) model of PFA EPN, derived from a metastatic cranial lesion. Patient and PDOX tumors were analyzed using immunohistochemistry, DNA methylation profiling, whole genome sequencing (WGS) and RNA sequencing. Both patient and PDOX tumors classified as PFA EPN by methylation profiling, and shared similar histological features consistent with this molecular subgroup. RNA sequencing revealed that gene expression patterns were maintained across the primary and metastatic tumors, as well as the PDOX. Copy number profiling revealed gains of chromosomes 7, 8 and 19, and loss of chromosomes 2q and 6q in the PDOX and matched patient tumor. No clinically significant single nucleotide variants were identified, consistent with the low mutation rates observed in PFA EPN. Overexpression of EZHIP RNA and protein, a common feature of PFA EPN, was also observed. Despite the aggressive nature of the tumor in the patient, this PDOX was unable to be maintained past two passages in vivo. Others who have successfully developed PDOX models report some of the lowest success rates for EPN compared to other pediatric brain cancer types attempted, with loss of tumorigenicity not uncommon, highlighting the challenge in propagating these tumors in the laboratory. Here, we discuss our collective experiences with PFA EPN PDOX model generation and propose potential approaches to improve future success in establishing preclinical EPN models","abstract":"Ependymomas (EPN) are the third most common malignant brain cancer in children. Treatment strategies for pediatric EPN have remained unchanged over recent decades, with 10-year survival rates stagnating at just 67% for children aged 0-14 years. Moreover, patients who survive treatment for the most common subtype of pediatric EPN (posterior fossa A (PFA)), often suffer long-term neurological side effects as a result of therapy. It is evident that there is a need for safer, more effective treatments for pediatric EPN patients. There are ten distinct subgroups of EPN, each with their own molecular and prognostic features. To identify and facilitate the testing of new treatments for EPN, in vivo laboratory models representative of the diverse molecular subtypes are required. Here, we describe the establishment of a patient-derived orthotopic xenograft (PDOX) model of PFA EPN, derived from a metastatic cranial lesion. Patient and PDOX tumors were analyzed using immunohistochemistry, DNA methylation profiling, whole genome sequencing (WGS) and RNA sequencing. Both patient and PDOX tumors classified as PFA EPN by methylation profiling, and shared similar histological features consistent with this molecular subgroup. RNA sequencing revealed that gene expression patterns were maintained across the primary and metastatic tumors, as well as the PDOX. Copy number profiling revealed gains of chromosomes 7, 8 and 19, and loss of chromosomes 2q and 6q in the PDOX and matched patient tumor. No clinically significant single nucleotide variants were identified, consistent with the low mutation rates observed in PFA EPN. Overexpression of EZHIP RNA and protein, a common feature of PFA EPN, was also observed. Despite the aggressive nature of the tumor in the patient, this PDOX was unable to be maintained past two passages in vivo. Others who have successfully developed PDOX models report some of the lowest success rates for EPN compared to other pediatric brain cancer types attempted, with loss of tumorigenicity not uncommon, highlighting the challenge in propagating these tumors in the laboratory. Here, we discuss our collective experiences with PFA EPN PDOX model generation and propose potential approaches to improve future success in establishing preclinical EPN models","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-06T04:38:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006845","title":"The genome-wide mutational consequences of DNA hypomethylation","description":null,"abstract":"DNA methylation is important for establishing and maintaining cell identity and for genomic stability. This is achieved by regulating the accessibility of regulatory and transcriptional elements and the compaction of subtelomeric, centromeric, and other inactive genomic regions. Carcinogenesis is accompanied by a global loss in DNA methylation, which facilitates the transformation of cells. Cancer hypomethylation may also cause genomic instability, for example through interference with the protective function of telomeres and centromeres. However, understanding the role(s) of hypomethylation in tumor evolution is incomplete because the precise mutational consequences of global hypomethylation have thus far not been systematically assessed. Here we made genome-wide inventories of all possible genetic variation that accumulates in single cells upon the long-term global hypomethylation by CRISPR/CAS9-mediated conditional knockdown of DNMT1. Depletion of DNMT1 results in a genomewide reduction in DNA methylation levels. Hypomethylated cells show reduced proliferation rates, reactivation of the inactive X-chromosome and abnormal nuclear morphologies. Prolonged hypomethylation is accompanied by increased chromosomal instability. However, there is no increase in mutational burden, enrichment for certain mutational signatures or structural changes to the genome. We conclude that the primary consequence of global hypomethylation is chromosomal instability and does not necessarily lead to other small-scale or structural mutational effects.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-06T08:09:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006846","title":"CD3 positive T cells isolated from blood after dry immersion of eight healthy volunteers","description":null,"abstract":"The next step of deep space exploration is manned missions to Moon and Mars. For safe space missions for crew members, it is important to better understand the impact of space flight on the immune system, how to prevent and counteract them. We here studied the effects of 21 days dry immersion (DI) bed exposure on the transcriptomes of T cell isolated from blood samples of eight healthy volunteers. Samples were collected at day 7 before DI, at day 7, 14, and 21 during DI, and at day 7 post-DI. RNA sequencing of CD3+ T cells revealed transcriptional alterations across all time points, with the most drastic changes occurring 14 days after DI exposure. Established T cell gene subsets for differentiation and activation such as CD69, JUNB, and SOCS1/3 were downregulated. Among the upregulated genes were IL2RA, IL2RB, and IL7RA, encoding the IL-2 and IL-7 receptors, and their transcriptional regulator ETS-1, needed for naïve T cell proliferation and differentiation. At day 21, CD3+ T cell transcriptomes showed evidence of adaptation with a transcriptional profile resembling that of 7 days pre-DI. At 7 days post-DI, T cells had changes in gene transcription comparable to the alterations found at 7 and 14 days of DI. This data suggests that T cells adapt by rewiring their transcriptomes in response to simulated weightlessness, and that remodeling queues persist when re-exposed to normal gravity.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006847","title":"scRNASeq of human innate lymphoid cells from different compartments","description":"Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) cells and ILC1s. We identifiy a population of “liver-type” ILC1s with transcriptional, phenotypic, and functional features distinct from those of conventional and liver-resident NK cells as well as from other previously described human ILC1 subsets. LT-ILC1s were CD49a+CD94+CD200R1+, expressed the transcription factor T-BET, do not express the activating receptor NKp80, or the transcription factor EOMES. Similar to NK cells, liver-type ILC1s produce IFN-γ, TNF-α, and GM-CSF; however, liver-type ILC1s also produce IL-2 and lack perforin and granzyme B. Liver- type ILC1s are expanded in cirrhotic liver tissues, and they can be produced from blood-derived ILC precursors in vitro in the presence of TGF-β1 and liver sinusoidal endothelial cells. Cells with similar signature and function can also be found in tonsil and intestinal tissues. Collectively, our study identifies and classifies a population of human cross-tissue ILC1s.","abstract":"Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) cells and ILC1s. We identifiy a population of “liver-type” ILC1s with transcriptional, phenotypic, and functional features distinct from those of conventional and liver-resident NK cells as well as from other previously described human ILC1 subsets. LT-ILC1s were CD49a+CD94+CD200R1+, expressed the transcription factor T-BET, do not express the activating receptor NKp80, or the transcription factor EOMES. Similar to NK cells, liver-type ILC1s produce IFN-γ, TNF-α, and GM-CSF; however, liver-type ILC1s also produce IL-2 and lack perforin and granzyme B. Liver- type ILC1s are expanded in cirrhotic liver tissues, and they can be produced from blood-derived ILC precursors in vitro in the presence of TGF-β1 and liver sinusoidal endothelial cells. Cells with similar signature and function can also be found in tonsil and intestinal tissues. Collectively, our study identifies and classifies a population of human cross-tissue ILC1s.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-06T10:06:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006848","title":"cfDNA dataset from extracelular vesicles and paired non-fractionated samples","description":"Liquid biopsies contain multiple analytes that can be mined to improve the detection and management of cancer. Beyond cell-free DNA (cfDNA), mutations have been detected in DNA associated with extracellular vesicles (EV-DNA). The genome-wide composition and structure of EV-DNA remains poorly characterized, and whether circulating EVs are enriched in tumor signal compared to unfractionated cfDNA is still unclear. \nHere, using whole genome sequencing from selected lung cancer patients with a relatively high cfDNA tumor content &gt;5%, we determined that the tumor fraction and heterogeneity are comparable between DNA associated with small (&lt;200 nm) EVs and matched plasma cfDNA. DNA in EV fractions, obtained with standardized size-exclusion chromatography, are comprised of short ~150-180 bp fragments and long &gt;1000 bp fragments that are poor in tumor signal. Other fractions only exhibit short fragments with similar tumor DNA content. The composition in bases at the end of EV-DNA fragments, as well as their fragmentation patterns are similar to total plasma cfDNA. Mitochondrial DNA however is relatively enriched in EV fractions. \nOur results suggests that cfDNA in plasma may be of dual nature, either bound to proteins (including the nucleosome) but also associated to EVs. cfDNA associated to small EV (including exosomes) is however not preferentially enriched in tumor signal.","abstract":"Liquid biopsies contain multiple analytes that can be mined to improve the detection and management of cancer. Beyond cell-free DNA (cfDNA), mutations have been detected in DNA associated with extracellular vesicles (EV-DNA). The genome-wide composition and structure of EV-DNA remains poorly characterized, and whether circulating EVs are enriched in tumor signal compared to unfractionated cfDNA is still unclear. \nHere, using whole genome sequencing from selected lung cancer patients with a relatively high cfDNA tumor content &gt;5%, we determined that the tumor fraction and heterogeneity are comparable between DNA associated with small (&lt;200 nm) EVs and matched plasma cfDNA. DNA in EV fractions, obtained with standardized size-exclusion chromatography, are comprised of short ~150-180 bp fragments and long &gt;1000 bp fragments that are poor in tumor signal. Other fractions only exhibit short fragments with similar tumor DNA content. The composition in bases at the end of EV-DNA fragments, as well as their fragmentation patterns are similar to total plasma cfDNA. Mitochondrial DNA however is relatively enriched in EV fractions. \nOur results suggests that cfDNA in plasma may be of dual nature, either bound to proteins (including the nucleosome) but also associated to EVs. cfDNA associated to small EV (including exosomes) is however not preferentially enriched in tumor signal.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-06T10:33:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006849","title":"Exploring responses of glioblastoma patient-derived cell cultures to drugs reveals new therapeutic opportunities","description":null,"abstract":"Glioblastomas (GBM) are common primary brain tumors in adults. Despite advances in neurosurgery, radio- and\nchemotherapy, the median survival of GBM patients remains 15 months. Several molecular GBM subtypes\nassociated with alterations of signaling pathways, affecting patient survival and responses to treatments were\ndefined. Recent large-scale genomic, transcriptomic and epigenetic analyses have shown the cellular and\nmolecular heterogeneity of GBMs, which hampers the outcomes of standard therapies. We have derived 13\nGBM-derived cell cultures from fresh tumor specimens and characterized them molecularly using RNAseq,\nimmunoblotting and immunocytochemistry. Evaluation of proneural (OLIG2, IDH1 R132H , TP53 and PDGFRα),\nclassical (EGFR) and mesenchymal markers (CHI3L1/YKL40, CD44 and phospho-STAT3), as well as expression\nof pluripotency (SOX2, OLIG2, NESTIN) and differentiation (GFAP, MAP2, β-Tubulin III) markers revealed the\nstriking inter-tumor heterogeneity of primary GBM cell cultures. Upregulated expression of VIMENTIN, N-\nCADHERIN and CD44 at mRNA/protein levels suggested increased epithelial to mesenchymal transition (EMT) in\nmost studied cell cultures. The effects of temozolomide (TMZ) or doxorubicin (DOX) were tested in three GBM-\nderived cell cultures with different methylation status of the MGMT promoter. Amongst TMZ- or DOX-treated\ncultures the strongest accumulation of apoptotic markers: caspase 7 and PARP was found in WG4 cells with\nmethylated MGMT suggesting that its methylation status predicts vulnerability to both drugs. As many GBM-\nderived cells showed high EGFR levels, we tested the effects of AG1478, an EGFR inhibitor, on downstream\nsignaling pathways. Interestingly, AG1478 reduced active, phospho-STAT3 levels and inhibition of active STAT3\naugmented antitumor effects of DOX in three tested cell cultures. Altogether, our findings show that GBM-derived\ncell cultures mimic the considerable tumor heterogeneity and identifying patient-specific signaling vulnerabilities\nallows for a combinatorial treatment overcoming therapy resistance.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006850","title":"Exploring responses of Glioblastoma patient-derived cell cultures to drugs reveals new therapeutic opportunities","description":null,"abstract":"Glioblastomas (GBM) are common primary brain tumors in adults. Despite advances in neurosurgery, radio- and\nchemotherapy, the median survival of GBM patients remains 15 months. Several molecular GBM subtypes\nassociated with alterations of signaling pathways, affecting patient survival and responses to treatments were\ndefined. Recent large-scale genomic, transcriptomic and epigenetic analyses have shown the cellular and\nmolecular heterogeneity of GBMs, which hampers the outcomes of standard therapies. We have derived 13\nGBM-derived cell cultures from fresh tumor specimens and characterized them molecularly using RNAseq,\nimmunoblotting and immunocytochemistry. Evaluation of proneural (OLIG2, IDH1 R132H , TP53 and PDGFRα),\nclassical (EGFR) and mesenchymal markers (CHI3L1/YKL40, CD44 and phospho-STAT3), as well as expression\nof pluripotency (SOX2, OLIG2, NESTIN) and differentiation (GFAP, MAP2, β-Tubulin III) markers revealed the\nstriking inter-tumor heterogeneity of primary GBM cell cultures. Upregulated expression of VIMENTIN, N-\nCADHERIN and CD44 at mRNA/protein levels suggested increased epithelial to mesenchymal transition (EMT) in\nmost studied cell cultures. The effects of temozolomide (TMZ) or doxorubicin (DOX) were tested in three GBM-\nderived cell cultures with different methylation status of the MGMT promoter. Amongst TMZ- or DOX-treated\ncultures the strongest accumulation of apoptotic markers: caspase 7 and PARP was found in WG4 cells with\nmethylated MGMT suggesting that its methylation status predicts vulnerability to both drugs. As many GBM-\nderived cells showed high EGFR levels, we tested the effects of AG1478, an EGFR inhibitor, on downstream\nsignaling pathways. Interestingly, AG1478 reduced active, phospho-STAT3 levels and inhibition of active STAT3\naugmented antitumor effects of DOX in three tested cell cultures. Altogether, our findings show that GBM-derived\ncell cultures mimic the considerable tumor heterogeneity and identifying patient-specific signaling vulnerabilities\nallows for a combinatorial treatment overcoming therapy resistance.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006851","title":"Multiregion Whole Exome and Smart-Seq3 single cell RNA sequencing of  Breast Tumors","description":"Multiple regions were cut out of each tumor extracted form  breast cancer patients and two experiments were run:\n\n- Whole exome sequencing on each of the regions plus an adjacent normal tissue sample\n- Smart-Seq3 Single cell RNA sequencing on EPCAM+ CD45- sorted cells from different tumor regions","abstract":"Multiple regions were cut out of each tumor extracted form  breast cancer patients and two experiments were run:\n\n- Whole exome sequencing on each of the regions plus an adjacent normal tissue sample\n- Smart-Seq3 Single cell RNA sequencing on EPCAM+ CD45- sorted cells from different tumor regions","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-06T14:34:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006852","title":"Whole Exome sequencing, bulk RNA sequencing and single cell RNA sequencing","description":null,"abstract":"Purpose: Genomic studies have identified new subsets of aggressive prostate cancer (PCa) with poor prognosis (e.g., neuroendocrine prostate cancer [NEPC], PCa with DNA Damage Response (DDR) alterations or PCa resistant to androgen-receptor pathway inhibitors [ARPI]). Development of novel therapies relies on the availability of relevant preclinical models. \n\nExperimental Design: NEPC (n = 5), DDR (n = 7), MSI-high (n=1) patient-derived xenografts (PDXs) were established from 51 patients with metastatic PCa enrolled in MATCH-R trial (NCT NCT02517892). PDX-derived organoids (PDXO) (n=16) and patient-derived organoids (PDO) (n=6) were developed to perform drug screening. Histopathology and treatment response were characterized. Molecular profiling was performed by whole-exome sequencing (WES, n =13), RNA sequencing (n =13), and single-cell RNA sequencing (n = 14). WES and RNA-seq data from patient tumors were compared with the models.\n\nResults: Our PDXs captured both common and rare molecular phenotypes as well as their molecular drivers, including alterations of BRCA2, CDK12, MSI-high status and NEPC. RNA sequencing profiling demonstrated broad representation of PCa subtypes. ScRNA-seq indicate that PDXs reproduce the cellular and molecular intra tumor heterogeneity. WES of matched patient tumors showed preservation of most genetic driver alterations. PDXOs and PDOs preserve drug sensitivity of the matched tissue and can be used to determine drug sensitivity.\n\nConclusions: Our models reproduce the phenotypic and genomic features of both common and aggressive PCa variants and capture their molecular heterogeneity. Successfully developed aggressive-variants PCa preclinical models provide an important preclinical tool to predict tumor response to anti-cancer therapy and study mechanisms of resistance.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006853","title":"Functional_changes_associated_with_drivers_in_chronic_liver_disease__LCM_RNAseq_","description":"Recently, recurrent mutations in genes involved in lipid metabolism and insulin pathway have been identified in the liver of patients with non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ARLD). While preliminary data suggests that these mutations are pathogenic and may be contributing to disease phenotype, the functional consequences of these abberrations are not fully understood. This study will aim to characterize the downstream effects of somatic mutations recurrent in liver tissue of patients with chronic liver disease. The data in this study will be generated by RNA sequencing of laser capture microdissections. The gene expression data will be then matched to genomic and lipidomic data from adjacent tissue sections to infer genotype-phenotype associations.","abstract":"This study will aim to characterize the downstream effects of somatic mutations recurrent in liver tissue of patients with chronic liver disease. The data in this study will be generated by RNA sequencing of laser capture microdissections. The gene expression data will be then matched to genomic and lipidomic data from adjacent tissue sections to infer genotype-phenotype associations.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006854","title":"Platelets sequester extracellular DNA, capturing tumour-derived and free fetal DNA","description":null,"abstract":"Platelets are small (2 – 5 μm), multi-functional cells that originate from megakaryocytes in the bone marrow and lung1. Platelets are anucleate but contain RNAs derived from parent megakaryocytes and the necessary translational machinery for protein synthesis. During cell death and aberrant mitosis, nucleated cells release chromosomal DNA that is rapidly fragmented, resulting in ‘cell free’ DNA in plasma (cfDNA). An excess of cfDNA is deleterious. Given their ability to sense and internalize pathogen-derived nucleic acids, we hypothesized that platelets may play a role in the clearance of endogeneous cfDNA. Here we reveal that despite the absence of a nucleus, platelets contain a repertoire of DNA fragments that map across the nuclear genome, in addition to mitochondrial DNA. We show that this DNA is acquired from non-megakaryocyte lineage cells, demonstrating the presence of fetal DNA in maternal platelets and cancer cell-derived DNA in platelets from patients with pre-malignant and overt solid cancers. This study establishes a role for platelets in the sequestration of cfDNA, an aspect of platelet biology that has not previously been highlighted, with broad applicability for minimally-invasive liquid biopsy. As platelets are readily isolated and continuously circulate through tissues, they are ideal ‘sentinels’ for genetic perturbations.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-06T18:19:18+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006855","title":"Analyzing the expression profiles of genes in ureters with and without indwelling stents using RNAseq ","description":"The objective of the work is to explore the pathways and mechanisms driving inflammation and fibrosis in stented ureters. In total, 6 pigs underwent cystoscopic unilateral ureteral stent insertion for 14 days. Ureteral tissue was harvested in 3 pigs, while the remaining 3 pigs had their stents removed, and were recovered for 7 days. Three separate pigs served as controls. Stents cause significant inflammation and fibrosis of ureters. Gene set enrichment analysis confirmed fibrotic changes and tissue proliferation and suggests that epithelial-mesenchymal transition is a driver of fibrosis.","abstract":"The objective of the work is to explore the pathways and mechanisms driving inflammation and fibrosis in stented ureters. In total, 6 pigs underwent cystoscopic unilateral ureteral stent insertion for 14 days. Ureteral tissue was harvested in 3 pigs, while the remaining 3 pigs had their stents removed, and were recovered for 7 days. Three separate pigs served as controls. Stents cause significant inflammation and fibrosis of ureters. Gene set enrichment analysis confirmed fibrotic changes and tissue proliferation and suggests that epithelial-mesenchymal transition is a driver of fibrosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-06T20:01:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006856","title":"Early on-treatment changes in circulating tumor DNA fraction and response to enzalutamide or abiraterone in metastatic castration-resistant prostate cancer","description":"On-treatment circulating tumor DNA (ctDNA) quantification is touted as a surrogate biomarker for understanding metastatic cancer response to systemic therapy, but there is relatively little supporting data from standardized patient cohorts. Here, in a prospective observational cohort, we demonstrate that 4-week on-treatment changes in plasma ctDNA levels can accurately identify metastatic castration-resistant prostate cancer that will progress within 6 months of initiating first-line abiraterone or enzalutamide treatment. On-treatment ctDNA measurements outperformed existing clinical variables for predicting disease response and were also closely associated with differential overall survival. Although optimal timing of blood collections and thresholds for ctDNA detection will require further testing, our data highlights the potential for sequential ctDNA measurements to provide an early and reliable read-out for therapy response. The high accuracy of this information suggests that ctDNA could be useful for guiding clinical trials of therapy changes in initially non-responsive metastatic cancers.","abstract":"On-treatment circulating tumor DNA (ctDNA) quantification is touted as a surrogate biomarker for understanding metastatic cancer response to systemic therapy, but there is relatively little supporting data from standardized patient cohorts. Here, in a prospective observational cohort, we demonstrate that 4-week on-treatment changes in plasma ctDNA levels can accurately identify metastatic castration-resistant prostate cancer that will progress within 6 months of initiating first-line abiraterone or enzalutamide treatment. On-treatment ctDNA measurements outperformed existing clinical variables for predicting disease response and were also closely associated with differential overall survival. Although optimal timing of blood collections and thresholds for ctDNA detection will require further testing, our data highlights the potential for sequential ctDNA measurements to provide an early and reliable read-out for therapy response. The high accuracy of this information suggests that ctDNA could be useful for guiding clinical trials of therapy changes in initially non-responsive metastatic cancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-07T01:13:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006857","title":"Rifaximin stimulates nitrogen detoxification by PXR-independent mechanisms in human small intestinal organoids","description":"To study the effects of rifaximin on human small intestinal (hSI) organoids, we performed RNAseq in PXR knockdown hSI compared to control hSI.","abstract":"To study the effects of rifaximin on human small intestinal (hSI) organoids, we performed RNAseq in PXR knockdown hSI compared to control hSI.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-07T09:43:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006858","title":"Genome_Wide_CRISPR_Screens_to_Establish_SGE_Candidate_Target_Genes_in_T_cell_Line_Models","description":"We propose to perform 3 genome-wide CRISPR screens using pre-established MinLib Guide library (Goncalves et al., 2021) in Jurkat T-cell Line and Primary T-cells using a T-cell relevant phenotype.","abstract":"T-cell lines are widely-used as models for assessing T-cell function. The Jurkat cell line is one of the most studied and characterised. However, T-cell lines are immortalised and cell signalling pathways intrinsically dysregulated, thus limiting their translatability to primary cell biology.\nWe aim to perform three pooled genome-wide CRISPR screens in Cas9+ Jurkat cells and primary T-cells in order to identify candidate target genes. These screens will assess two phenotypes in Jurkat cells; essentiality and a T-cell relevant phenotype.\nGene hits from the independent screens can be compared to identify which genes could be translatable from the T-cell line model to primary T-cell biology. These genes can be taken forward for investigations in the T-cell line models having validate the effects observed will be representative. Such investigations include saturation genome editing, whereby the effect of individual variants within a target gene are evaluated to establish a variant effect map (Findlay et al., 2018).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006859","title":"Low Grade Serous Ovarian Cancer Exome Sequencing Scotland and The Netherlands","description":null,"abstract":"To characterize the most common variants present in LGSOC from samples collected in Scotland and The Netherlands","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006860","title":"Exome sequencing of HCV+ lymphoma","description":"The present retrospective study aimed to explore the genetic landscape of a well-characterized series of 34 HCV-associated B-cell lymphomas from the observational multicentric ANRS HC-13 Lympho-C Study using tumor and matched germline whole exome sequencing (WES). It reported the first series of VHC-positive lymphoma patients analyzed by WES. Our results provide an overview of the genetic landscape associated to HCV-related B-cell lymphomas and highlight some novel putative candidate genes.","abstract":"The present retrospective study aimed to explore the genetic landscape of a well-characterized series of 34 HCV-associated B-cell lymphomas from the observational multicentric ANRS HC-13 Lympho-C Study using tumor and matched germline whole exome sequencing (WES). It reported the first series of VHC-positive lymphoma patients analyzed by WES. Our results provide an overview of the genetic landscape associated to HCV-related B-cell lymphomas and highlight some novel putative candidate genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-07T10:48:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006861","title":"DERMATLAS__Hidradenocarcinoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are hidradenocarcinoma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are hidradenocarcinoma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006862","title":"Infinity_Illumina_for_blood_colonies_EMseq","description":"Technology assessment by Mike Quail - trial samples. Infinity Illumina synthetic reads","abstract":"Technology assessment by Mike Quail - trial samples. Infinity Illumina synthetic reads","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006863","title":"Childhood B-cell acute lymphoblastic leukemia genomic and transcriptomic data","description":"The aim of the two studies was: 1) to genetically characterise childhood leukemia patients that lacked established cytogenetic abnormalities (termed B-other leukemia) and assess the clinical features of recurrent genetic abnormalities. 2) Assess the accuracy of whole genome sequencing as a diagnostic genetic test in childhood leukemia, relative to other traditional methods (karyotyping, FISH, MLPA) and whole transcriptome sequencing. As a result, this study includes targeted DNA-sequencing, whole genome sequencing and whole transcriptome sequencing data on childhood leukemia patients enrolled on UK clinical trials (UKALL2003 and UKALL2011).","abstract":"The aim of the two studies was: 1) to genetically characterise childhood leukemia patients that lacked established cytogenetic abnormalities (termed B-other leukemia) and assess the clinical features of recurrent genetic abnormalities. 2) Assess the accuracy of whole genome sequencing as a diagnostic genetic test in childhood leukemia, relative to other traditional methods (karyotyping, FISH, MLPA) and whole transcriptome sequencing. As a result, this study includes targeted DNA-sequencing, whole genome sequencing and whole transcriptome sequencing data on childhood leukemia patients enrolled on UK clinical trials (UKALL2003 and UKALL2011).","study_type":"Cancer Genomics","pubmed_ids":[36658389,36550215],"external_links":null,"is_released":true,"released_date":"2024-11-25T11:27:05.077467+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006864","title":"T cell landscape definition by multi-omics identifies galectin-9 as novel immunotherapy target in chronic lymphocytic leukemia (CLL)","description":"Failure of immunotherapy after applying checkpoint inhibitors or CAR-T cells is linked to T cell exhaustion. Here, we explored the T cell landscape in chronic lymphocytic leukemia (CLL) by single-cell omics analyses of blood, bone marrow and lymph node samples of patients and spleen samples of a CLL mouse model. By single-cell RNA- sequencing, mass cytometry (CyTOF), and multiplex image analysis of tissue microarrays, we defined the spectrum of phenotypes and transcriptional programs of T cells and and their differentiation state trajectories. We identified disease-specific accumulation of distinct regulatory T cell subsets and T cells harboring an exhausted phenotype exclusively in the CLL lymph node tissue. Integration of TCR data revealed a clonal expansion of CD8+ precursor exhausted T cells, suggesting their reactivity for CLL cells. Interactome analyses identified the TIM3 ligand Galectin-9 as novel immunoregulatory molecule in CLL. Blocking of Galectin-9 in CLL-bearing mice slowed down disease development and reduced the number of TIM3 expressing T cells. Galectin-9 expression correlated with shorter survival of CLL patients. Thus, Galectin-9 contributes to immune escape in CLL and represents a novel target for immunotherapy.","abstract":"Failure of immunotherapy after applying checkpoint inhibitors or CAR-T cells is linked to T cell exhaustion. Here, we explored the T cell landscape in chronic lymphocytic leukemia (CLL) by single-cell omics analyses of blood, bone marrow and lymph node samples of patients and spleen samples of a CLL mouse model. By single-cell RNA- sequencing, mass cytometry (CyTOF), and multiplex image analysis of tissue microarrays, we defined the spectrum of phenotypes and transcriptional programs of T cells and and their differentiation state trajectories. We identified disease-specific accumulation of distinct regulatory T cell subsets and T cells harboring an exhausted phenotype exclusively in the CLL lymph node tissue. Integration of TCR data revealed a clonal expansion of CD8+ precursor exhausted T cells, suggesting their reactivity for CLL cells. Interactome analyses identified the TIM3 ligand Galectin-9 as novel immunoregulatory molecule in CLL. Blocking of Galectin-9 in CLL-bearing mice slowed down disease development and reduced the number of TIM3 expressing T cells. Galectin-9 expression correlated with shorter survival of CLL patients. Thus, Galectin-9 contributes to immune escape in CLL and represents a novel target for immunotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-08T15:15:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006865","title":"Atypical teratoid/rhabdoid tumoroids reveal subgroup-specific drug vulnerabilities WGS","description":"Atypical teratoid/rhabdoid tumors (ATRTs) represent a rare, but aggressive pediatric brain tumor entity. They are genetically uniquely defined by alterations in the SWI/SNF chromatin remodeling complex members SMARCB1 or SMARCA4. ATRTs can be further classified in different molecular subgroups based on their epigenetic profiles. Although recent studies suggest that the different subgroups have distinct clinical features, subgroup-specific treatment regimens have not been developed thus far. This is hampered by the lack of pre-clinical in vitro models representative of the different molecular subgroups. Here, we describe the establishment of ATRT tumoroid models from the ATRT-MYC and ATRT-SHH subgroups. We demonstrate that ATRT tumoroids retain subgroup-specific epigenetic and gene expression profiles. High throughput drug screens on our ATRT tumoroids revealed distinct drug sensitivities between and within ATRT-MYC and ATRT-SHH subgroups. Whereas ATRT-MYC universally displayed high sensitivity to multi-targeted tyrosine kinase inhibitors, ATRT-SHH showed a more heterogeneous response with a subset showing high sensitivity to Notch inhibitors, which corresponded to high expression of Notch receptors. Our ATRT tumoroids represent the first pediatric brain tumor organoid model, providing a representative pre-clinical model which enables the development of subgroup-specific therapies.","abstract":"Atypical teratoid/rhabdoid tumors (ATRTs) represent a rare, but aggressive pediatric brain tumor entity. They are genetically uniquely defined by alterations in the SWI/SNF chromatin remodeling complex members SMARCB1 or SMARCA4. ATRTs can be further classified in different molecular subgroups based on their epigenetic profiles. Although recent studies suggest that the different subgroups have distinct clinical features, subgroup-specific treatment regimens have not been developed thus far. This is hampered by the lack of pre-clinical in vitro models representative of the different molecular subgroups. Here, we describe the establishment of ATRT tumoroid models from the ATRT-MYC and ATRT-SHH subgroups. We demonstrate that ATRT tumoroids retain subgroup-specific epigenetic and gene expression profiles. High throughput drug screens on our ATRT tumoroids revealed distinct drug sensitivities between and within ATRT-MYC and ATRT-SHH subgroups. Whereas ATRT-MYC universally displayed high sensitivity to multi-targeted tyrosine kinase inhibitors, ATRT-SHH showed a more heterogeneous response with a subset showing high sensitivity to Notch inhibitors, which corresponded to high expression of Notch receptors. Our ATRT tumoroids represent the first pediatric brain tumor organoid model, providing a representative pre-clinical model which enables the development of subgroup-specific therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-09T10:40:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006866","title":"Atypical teratoid/rhabdoid tumoroids reveal subgroup-specific drug vulnerabilities RNA-Seq","description":"Atypical teratoid/rhabdoid tumors (ATRTs) represent a rare, but aggressive pediatric brain tumor entity. They are genetically uniquely defined by alterations in the SWI/SNF chromatin remodeling complex members SMARCB1 or SMARCA4. ATRTs can be further classified in different molecular subgroups based on their epigenetic profiles. Although recent studies suggest that the different subgroups have distinct clinical features, subgroup-specific treatment regimens have not been developed thus far. This is hampered by the lack of pre-clinical in vitro models representative of the different molecular subgroups. Here, we describe the establishment of ATRT tumoroid models from the ATRT-MYC and ATRT-SHH subgroups. We demonstrate that ATRT tumoroids retain subgroup-specific epigenetic and gene expression profiles. High throughput drug screens on our ATRT tumoroids revealed distinct drug sensitivities between and within ATRT-MYC and ATRT-SHH subgroups. Whereas ATRT-MYC universally displayed high sensitivity to multi-targeted tyrosine kinase inhibitors, ATRT-SHH showed a more heterogeneous response with a subset showing high sensitivity to Notch inhibitors, which corresponded to high expression of Notch receptors. Our ATRT tumoroids represent the first pediatric brain tumor organoid model, providing a representative pre-clinical model which enables the development of subgroup-specific therapies.","abstract":"Atypical teratoid/rhabdoid tumors (ATRTs) represent a rare, but aggressive pediatric brain tumor entity. They are genetically uniquely defined by alterations in the SWI/SNF chromatin remodeling complex members SMARCB1 or SMARCA4. ATRTs can be further classified in different molecular subgroups based on their epigenetic profiles. Although recent studies suggest that the different subgroups have distinct clinical features, subgroup-specific treatment regimens have not been developed thus far. This is hampered by the lack of pre-clinical in vitro models representative of the different molecular subgroups. Here, we describe the establishment of ATRT tumoroid models from the ATRT-MYC and ATRT-SHH subgroups. We demonstrate that ATRT tumoroids retain subgroup-specific epigenetic and gene expression profiles. High throughput drug screens on our ATRT tumoroids revealed distinct drug sensitivities between and within ATRT-MYC and ATRT-SHH subgroups. Whereas ATRT-MYC universally displayed high sensitivity to multi-targeted tyrosine kinase inhibitors, ATRT-SHH showed a more heterogeneous response with a subset showing high sensitivity to Notch inhibitors, which corresponded to high expression of Notch receptors. Our ATRT tumoroids represent the first pediatric brain tumor organoid model, providing a representative pre-clinical model which enables the development of subgroup-specific therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-09T10:54:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006867","title":"Study","description":null,"abstract":"Study","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006868","title":"Smart-seq3 scRNA-seq of cells from primary (OV2295) and metastatic (OV2295R2) high-grade serous ovarian cancer cell-line","description":"In this project, single cells extracted from two  high-grade serous ovarian cancer cell-lines,  one primary (OV2295) and one metastatic (OV2295R2), where split into two 384 well plates and libraries were prepared using Smart-seq3 single cell RNA sequencing (Hagemann-Jensen et al, 2020).","abstract":"In this project, single cells extracted from two  high-grade serous ovarian cancer cell-lines,  one primary (OV2295) and one metastatic (OV2295R2), where split into two 384 well plates and libraries were prepared using Smart-seq3 single cell RNA sequencing (Hagemann-Jensen et al, 2020).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-12T15:37:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006869","title":"Whole genome sequencing to detect spontaneous acquired mutations in mismatch repair-deficient human colon organoids","description":null,"abstract":"Individual outgrowing organoids surviving the medium-based selection were manually picked and propagated as clonal lines for a couple of passages to avoid unexpected mutation accumulation before being harvested for WGS/WES. 1 µg of DNA was used for WGS/WES by Agilent SureSelect V7 kit, with 8Gb per sample (50X average mapped) data throughput, sequencing on NovaSeq 150PE","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006870","title":"Population_based_analysis_of_POT1_variants_in_a_cutaneous_melanoma_case_control_cohort","description":"Pathogenic germline variants in the protection of telomeres 1 gene (POT1) have been associated with predisposition to a range of tumor types, including melanoma, glioma, leukemia and cardioangiosarcoma. We sequenced all coding exons of the POT1 gene in 2,929 European-descent melanoma cases and 3,298 controls, identifying 43 protein-changing genetic variants. We performed functional studies on each of these variants and explored their possible contribution to disease risk.","abstract":"Pathogenic germline variants in the protection of telomeres 1 gene (POT1) have been associated with predisposition to a range of tumor types, including melanoma, glioma, leukemia and cardioangiosarcoma. We sequenced all coding exons of the POT1 gene in 2,929 European-descent melanoma cases and 3,298 controls, identifying 43 protein-changing genetic variants. We performed functional studies on each of these variants and explored their possible contribution to disease risk.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-13T15:31:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006871","title":"RNAseq of paired primary and locally recurrent IDHwt GBM","description":"Perform RNAseq of paired primary and locally recurrent IDHwt GBM following standard treatment.","abstract":"Perform RNAseq of paired primary and locally recurrent IDHwt GBM following standard treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-14T10:19:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006872","title":"BE_screens_of_WRN_gene_in_MSI_models","description":"We will take advantage of a base-editing screening strategy to engineer mutations in the WRN gene by deep mutagenesis. Two MSI-H cell lines sensitive to WRNi will be genetically modified to express doxycycline-inducible ABE and CBE base editors through a knock-in strategy. Moreover, we will design a pooled library of ~4000 gRNAs targeting the WRN gene plus appropriate controls gRNAs. Library-transduced cells will be selected with WRNi to identify WRN mutations able to interfere with the activity of WRNi.","abstract":"The aim of this project is modeling acquired resisstance to WRN inhibitors by implementing a base-editing screening strategy to engineer mutations in the WRN gene by deep mutagenesis. Library-transduced MSI cells will be selected with WRN inhibitors to identify WRN mutations able to interfere with their activity.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-14T14:09:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006873","title":"Targeted DNA sequencing on 37 Merkel Cell Carcinomas from New Zealand with known Merkel cell polyomavirus status","description":"To determine the genomic landscape of NZ virus-negative MCCs (VN-MCC), assess genomic evolution in metastases, and catalogue the distribution of TP53 and RB1 variants from international studies.","abstract":"To determine the genomic landscape of NZ virus-negative MCCs (VN-MCC), assess genomic evolution in metastases, and catalogue the distribution of TP53 and RB1 variants from international studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-14T20:32:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006874","title":"WGS of MAPKi acquired resistant samples from patients and PDX models","description":"Blocking cancer genomic instability, which generates diverse variants that enable rapid adaptations, may prevent tumor escape from therapies. We show that, after MAPK inhibitor (MAPKi) therapy in patients and patient-derived xenografts, acquired-resistant genomes of metastatic cutaneous melanoma accumulate amplicons of resistance-driver, non-homologous end-joining (NHEJ), and homologous recombination repair (HRR) genes within complex genomic rearrangements (CGRs) and extrachromosomal circular DNAs (ecDNAs). Also, chromothriptic genomic regions enrich for mutations and may engender ecDNAs and CGRs. Overall, somatic mutations within ecDNA- and CGR-amplicons enrich for HRR signatures, and, in acquired resistance, ecDNA (versus CGR) mutations enrich for APOBEC3 signatures. Breakpoint-sequence analysis suggests NHEJ as critical to double-stranded DNA break repair underlying CGR and ecDNA formation. In vivo, NHEJ-targeting by a DNA-PKCS inhibitor prevented acquired MAPKi-resistance by reducing the size of ecDNAs and CGRs early on combination treatment. Thus, targeting the cause(s), as opposed to the consequences, of genomic instability prevents acquired resistance.","abstract":"Blocking cancer genomic instability, which generates diverse variants that enable rapid adaptations, may prevent tumor escape from therapies. We show that, after MAPK inhibitor (MAPKi) therapy in patients and patient-derived xenografts, acquired-resistant genomes of metastatic cutaneous melanoma accumulate amplicons of resistance-driver, non-homologous end-joining (NHEJ), and homologous recombination repair (HRR) genes within complex genomic rearrangements (CGRs) and extrachromosomal circular DNAs (ecDNAs). Also, chromothriptic genomic regions enrich for mutations and may engender ecDNAs and CGRs. Overall, somatic mutations within ecDNA- and CGR-amplicons enrich for HRR signatures, and, in acquired resistance, ecDNA (versus CGR) mutations enrich for APOBEC3 signatures. Breakpoint-sequence analysis suggests NHEJ as critical to double-stranded DNA break repair underlying CGR and ecDNA formation. In vivo, NHEJ-targeting by a DNA-PKCS inhibitor prevented acquired MAPKi-resistance by reducing the size of ecDNAs and CGRs early on combination treatment. Thus, targeting the cause(s), as opposed to the consequences, of genomic instability prevents acquired resistance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-15T03:21:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006875","title":"Kings_Hepatoblastoma_Behjati_WGS_Managed_Access","description":"A study of the development of liver based tumours.","abstract":"A study of the development of liver based tumours.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-15T11:41:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006876","title":"Kings_Hepatoblastoma_Behjati_RNA_Managed_Access","description":"A study of the development of liver based tumours.","abstract":"A study of the development of liver based tumours.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-15T10:45:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006877","title":"Kings_Hepatoblastoma_Behjati_Nanoseq_Managed_Access","description":"A study of the development of liver based tumours.","abstract":"A study of the development of liver based tumours.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-15T10:49:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006878","title":"Short-read whole genome sequencing identifies causative variants in most individuals with previously unexplained aniridia","description":null,"abstract":"Classical aniridia is a highly penetrant autosomal dominant disorder characterised by congenital absence of the iris, foveal hypoplasia, optic disc anomalies and an adult-onset progressive opacification of the cornea. &gt;90% of classical aniridia is caused by heterozygous, loss of function mutations affecting the PAX6 locus. Short-read whole genome sequencing was performed on 51 (39 affected) individuals from 37 different families who had screened negative for mutations in the PAX6 coding region. Likely causative mutations were identified in 22/37 (59%) families. In 19/22 families the causative genomic changes have an interpretable deleterious impact on the PAX6 locus. 1/19 has a heterozygous PAX6 frameshift variant missed on previous screens. 4/19 have single nucleotide variants affecting essential splice sites of PAX6 5’ non-coding exons. 2/19 have deep intronic SNV resulting in gain of a donor spice site. In 12/19 the causative mutations are large-scale structural variants (SV); 5 have partial or whole gene deletions of PAX6, 3 have deletions encompassing critical PAX6 cis-regulatory elements, 2 have balanced inversions with disruptive breakpoints within the PAX6 locus and 2 have complex rearrangements disrupting PAX6. The remaining 3/22 families have deletions encompassing FOXC1 (a known cause of atypical aniridia).  Seven of the causative mutations occurred de novo and one co-segregated with the familial aniridia. We were unable to establish inheritance status in the remaining probands. No plausibly causative SNVs were identified in PAX6 cis-regulatory elements. Whole genome sequencing has proven to be an effective diagnostic test in most individuals with previously unexplained aniridia.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006879","title":"Non-muscle Invasive Bladder Cancer Molecular Subtypes Predict Differential Response to Intravesical Bacillus Calmette-Guérin","description":"The recommended treatment for patients with high-risk non-muscle invasive bladder cancer (HR-NMIBC) is tumor resection followed by adjuvant Bacillus Calmette-Guérin (BCG) bladder instillations. However, only 50% of patients benefit from this therapy. In case of progression to advanced disease, patients must undergo a radical cystectomy with significant morbidity and have a poor clinical outcome. Identifying tumors least likely to respond to BCG can translate into alternative treatments, such as early radical cystectomy or novel targeted or immunotherapies. Here we present molecular profiling of 132 BCG-naive, HR-NMIBC patients, and 44 post-BCG recurrences (34 matched), which uncovered three distinct BCG Response Subtypes (BRS1-3). Patients with BRS3 tumors have reduced recurrence and progression-free survival compared to BRS1-2. BRS3 tumors expressed high EMT-basal markers and had an immunosuppresive profile, which was confirmed with spatial proteomics. Tumors which recurred post-BCG were enriched for BRS3. BRS stratification was validated in a second cohort of 151 BCG-naive HR-NMIBC patients and the molecular subtypes outperformed guideline recommended risk stratification based on clinicopathological variables. For clinical application, we validated that a commercially approved assay was able to accurately predict BRS3 tumors (AUROC 0.86). Our findings provide a potential clinical tool for improved identification of HR-NMIBC patients at the highest risk of progression, which can be used to select patients for early radical cystectomy or novel subtype-directed therapies.","abstract":"The recommended treatment for patients with high-risk non-muscle invasive bladder cancer (HR-NMIBC) is tumor resection followed by adjuvant Bacillus Calmette-Guérin (BCG) bladder instillations. However, only 50% of patients benefit from this therapy. In case of progression to advanced disease, patients must undergo a radical cystectomy with significant morbidity and have a poor clinical outcome. Identifying tumors least likely to respond to BCG can translate into alternative treatments, such as early radical cystectomy or novel targeted or immunotherapies. Here we present molecular profiling of 132 BCG-naive, HR-NMIBC patients, and 44 post-BCG recurrences (34 matched), which uncovered three distinct BCG Response Subtypes (BRS1-3). Patients with BRS3 tumors have reduced recurrence and progression-free survival compared to BRS1-2. BRS3 tumors expressed high EMT-basal markers and had an immunosuppresive profile, which was confirmed with spatial proteomics. Tumors which recurred post-BCG were enriched for BRS3. BRS stratification was validated in a second cohort of 151 BCG-naive HR-NMIBC patients and the molecular subtypes outperformed guideline recommended risk stratification based on clinicopathological variables. For clinical application, we validated that a commercially approved assay was able to accurately predict BRS3 tumors (AUROC 0.86). Our findings provide a potential clinical tool for improved identification of HR-NMIBC patients at the highest risk of progression, which can be used to select patients for early radical cystectomy or novel subtype-directed therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-15T13:44:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006880","title":"Transcriptomes_of_normal_and_neoplastic_breast_tissues","description":"LCM guided multiregion RNA sequencing of breast tissues to examine genotype-phenotype relationships in evolving cancers","abstract":"To understand the diverse evolutionary trajectories of healthy and cancerous breast tissue cells we are using spatially resolved molecular analyses in normal tissues and breast cancers from the earliest stage of disease (pre-invasive), through to the stages of tissue invasion. Laser capture microscopy and genomic profiling data has revealed the extent of genomic diversity in the breast samples studied here. In this study we will perform LCM of z-stack tissue sections to derive the genotype-phenotype relationships at play.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006881","title":"Atypical teratoid/rhabdoid tumoroids reveal subgroup-specific drug vulnerabilities DNA-Methylation","description":"Atypical teratoid/rhabdoid tumors (ATRTs) represent a rare, but aggressive pediatric brain tumor entity. They are genetically uniquely defined by alterations in the SWI/SNF chromatin remodeling complex members SMARCB1 or SMARCA4. ATRTs can be further classified in different molecular subgroups based on their epigenetic profiles. Although recent studies suggest that the different subgroups have distinct clinical features, subgroup-specific treatment regimens have not been developed thus far. This is hampered by the lack of pre-clinical in vitro models representative of the different molecular subgroups. Here, we describe the establishment of ATRT tumoroid models from the ATRT-MYC and ATRT-SHH subgroups. We demonstrate that ATRT tumoroids retain subgroup-specific epigenetic and gene expression profiles. High throughput drug screens on our ATRT tumoroids revealed distinct drug sensitivities between and within ATRT-MYC and ATRT-SHH subgroups. Whereas ATRT-MYC universally displayed high sensitivity to multi-targeted tyrosine kinase inhibitors, ATRT-SHH showed a more heterogeneous response with a subset showing high sensitivity to Notch inhibitors, which corresponded to high expression of Notch receptors. Our ATRT tumoroids represent the first pediatric brain tumor organoid model, providing a representative pre-clinical model which enables the development of subgroup-specific therapies.","abstract":"Atypical teratoid/rhabdoid tumors (ATRTs) represent a rare, but aggressive pediatric brain tumor entity. They are genetically uniquely defined by alterations in the SWI/SNF chromatin remodeling complex members SMARCB1 or SMARCA4. ATRTs can be further classified in different molecular subgroups based on their epigenetic profiles. Although recent studies suggest that the different subgroups have distinct clinical features, subgroup-specific treatment regimens have not been developed thus far. This is hampered by the lack of pre-clinical in vitro models representative of the different molecular subgroups. Here, we describe the establishment of ATRT tumoroid models from the ATRT-MYC and ATRT-SHH subgroups. We demonstrate that ATRT tumoroids retain subgroup-specific epigenetic and gene expression profiles. High throughput drug screens on our ATRT tumoroids revealed distinct drug sensitivities between and within ATRT-MYC and ATRT-SHH subgroups. Whereas ATRT-MYC universally displayed high sensitivity to multi-targeted tyrosine kinase inhibitors, ATRT-SHH showed a more heterogeneous response with a subset showing high sensitivity to Notch inhibitors, which corresponded to high expression of Notch receptors. Our ATRT tumoroids represent the first pediatric brain tumor organoid model, providing a representative pre-clinical model which enables the development of subgroup-specific therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-16T08:07:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006882","title":"HCA_Gut_Adult_RBC_RCN_Teichmann_DNA","description":"Animal studies have demonstrated that resident memory T (Trm) cells provide enhanced protective responses to a broad array of tissue-tropic pathogens, thus making Trm cells promising targets for novel vaccination strategies. However, the biological pathways that enable the long-term survival of Trm cells are poorly understood in humans. Here, we will employ a unique human intestinal transplantation setting that allows us to study the retention of persistent T cells in the grafts and the temporal development of resident T-cell populations from recruited recipient T cells. We will integrate high resolution transcriptomics, epigenetics, proteomics and immune repertoire single-cell data from purified intestinal T cells. These single-cell multiomics approaches will uncover the diversity and differentiation of the T cell populations in the human intestine, allowing us to temporally resolve the generation and maintenance of gut resident T cells.","abstract":"Animal studies have demonstrated that resident memory T (Trm) cells provide enhanced protective responses to a broad array of tissue-tropic pathogens, thus making Trm cells promising targets for novel vaccination strategies. However, the biological pathways that enable the long-term survival of Trm cells are poorly understood in humans. Here, we will employ a unique human intestinal transplantation setting that allows us to study the retention of persistent T cells in the grafts and the temporal development of resident T-cell populations from recruited recipient T cells. We will integrate high resolution transcriptomics, epigenetics, proteomics and immune repertoire single-cell data from purified intestinal T cells. These single-cell multiomics approaches will uncover the diversity and differentiation of the T cell populations in the human intestine, allowing us to temporally resolve the generation and maintenance of gut resident T cells","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006883","title":"ctDNA to predict risk of progression and death after trifluridin/tipiracil therapy","description":"Background. Late-line treatment in metastatic colorectal cancer (mCRC) can improve the prognosis. However, not every patient has a benefit and may experience severe side effects. Thus, predictive/prognostic biomarkers are urgently needed. Despite many promising results, the role of circulating tumor DNA (ctDNA) analysis in trifluridin/tipiracil (FTD/TPI) treated mCRC patients is so far still elusive.\nStudy design. This prospective non-interventional translational biomarker phase II study enrolled 30 metastatic CRC patients treated with FTD/TPI. The primary study aim was to identify a molecular biomarker to predict overall survival (OS) benefit upon FTD/TPI treatment.\nMethods. mCRC patients (60% male, 40% female) with FTD/TPI therapy were included. Molecular profiling in cell-free DNA from plasma was performed prior to treatment and on average 4, 8 and 12 weeks after FTD/TPI initiation. Tumor levels were assessed as the highest variant allele frequency (hVAF) and correlated with OS. Uni- and multivariate analyses for survival were performed with clinical variables. Multivariate analyses for survival and treatment efficacy were adjusted to age, gender and ECOG performance status. \nResults. Compared to previous data, our disease control rate of 30% was lower with a median OS of 8.1 months and a median PFS of 3.2 months. At baseline (BL) and the first two follow-ups (FU), a hVAF cut-off of 7.5% was most discriminative (BL HR 0.39 95% CI 0.16 - 0.98 P=0.0212, FU1 HR 0.30 95% CI 0.12 -0.77 P=0.0021, FU2 HR 0.23 95% CI 0.08-0.70 P=0.0004) whereas at the last follow-up the stratification was most pronounced at a 15% cut-off. An elevated hVAF trajectory over time was associated with a higher risk of death.\nConclusion. ctDNA is detectable in a high proportion of mCRC patients. Changes in ctDNA levels are associated with survival among FTD/TPI therapy and may identify patients who benefit most from treatment in these late-stage disease.","abstract":"Background. Late-line treatment in metastatic colorectal cancer (mCRC) can improve the prognosis. However, not every patient has a benefit and may experience severe side effects. Thus, predictive/prognostic biomarkers are urgently needed. Despite many promising results, the role of circulating tumor DNA (ctDNA) analysis in trifluridin/tipiracil (FTD/TPI) treated mCRC patients is so far still elusive.\nStudy design. This prospective non-interventional translational biomarker phase II study enrolled 30 metastatic CRC patients treated with FTD/TPI. The primary study aim was to identify a molecular biomarker to predict overall survival (OS) benefit upon FTD/TPI treatment.\nMethods. mCRC patients (60% male, 40% female) with FTD/TPI therapy were included. Molecular profiling in cell-free DNA from plasma was performed prior to treatment and on average 4, 8 and 12 weeks after FTD/TPI initiation. Tumor levels were assessed as the highest variant allele frequency (hVAF) and correlated with OS. Uni- and multivariate analyses for survival were performed with clinical variables. Multivariate analyses for survival and treatment efficacy were adjusted to age, gender and ECOG performance status. \nResults. Compared to previous data, our disease control rate of 30% was lower with a median OS of 8.1 months and a median PFS of 3.2 months. At baseline (BL) and the first two follow-ups (FU), a hVAF cut-off of 7.5% was most discriminative (BL HR 0.39 95% CI 0.16 - 0.98 P=0.0212, FU1 HR 0.30 95% CI 0.12 -0.77 P=0.0021, FU2 HR 0.23 95% CI 0.08-0.70 P=0.0004) whereas at the last follow-up the stratification was most pronounced at a 15% cut-off. An elevated hVAF trajectory over time was associated with a higher risk of death.\nConclusion. ctDNA is detectable in a high proportion of mCRC patients. Changes in ctDNA levels are associated with survival among FTD/TPI therapy and may identify patients who benefit most from treatment in these late-stage disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-16T12:24:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006884","title":"Molecular evolution of classic Hodgkin lymphoma revealed through whole genome sequencing of Hodgkin and Reed Sternberg cells","description":"Here we leveraged whole genome structural variant copy number analysis to report the first whole genome sequencing landscape of HRS cells and reconstruct the chronology and likely etiology\nof pathogenic events prior to the clinical diagnosis of cHL.","abstract":"Here we leveraged whole genome structural variant copy number analysis to report the first whole genome sequencing landscape of HRS cells and reconstruct the chronology and likely etiology\nof pathogenic events prior to the clinical diagnosis of cHL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-19T03:02:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006885","title":"Transcriptomic analysis of liver CD8+ T cells","description":"Sorted single CD8+T cells expressing CD14 from human liver for SMARTSeq2.\n\nLivers processed: Kucykowicz et al STAR Prot 2022:pubmed.ncbi.nlm.nih.gov/35516846/ \n\nPublished: Pallett et al Nature 2022\nTissue CD14+CD8+T-cells are reprogrammed by myeloid cells and modulated by LPS\n\nThe liver is bathed in bacterial products including LPS transported from the intestinal portal vasculature, but maintains a state of tolerance exploited by persistent pathogens and tumours1,2,3,4. The cellular basis mediating this tolerance, yet allowing a switch to immunity or immunopathology, needs to be better understood for successful immunotherapy of liver diseases. Here we show that a variable proportion of CD8+T-cells compartmentalised in the human liver co-stain for CD14 and other prototypic myeloid membrane proteins; CD14+CD8+T-cells preferentially accumulate within the donor pool in liver allografts, amongst hepatic virus-specific and tumour-infiltrating responses, and in cirrhotic ascites. CD14+CD8+T-cells exhibit increased turnover, activation and constitutive immunomodulatory features with high homeostatic IL-10/IL-2 production directly ex vivo, and an enhanced capacity to rapidly produce antiviral/anti-tumour cytokines upon TCR engagement. This CD14+CD8+T-cell profile can be recapitulated by acquisition of membrane proteins, including the LPS receptor complex, from mononuclear phagocytes, resulting in augmented tumour killing by TCR-redirected T-cells in vitro. CD14+CD8+T-cells express integrins and chemokine receptors favouring interactions with the local stroma, which can promote their induction through CXCL12. LPS can also increase the frequency of CD14+CD8+T-cells in vitro and in vivo, and skew their function towards the production of chemotactic and regenerative cytokines. Thus, bacterial products in the gut-liver axis and tissue stromal factors can tune liver immunity by driving myeloid instruction of CD8+T-cells with immunomodulatory capacity. \n\nFor the analysis of the single cell transcriptome two intrahepatic perfusate samples were isolated and frozen at -80 'C for storage prior to transportation to Newcastle, UK. Once thawed in pre-warmed HBSS containing 0.001% DNaseI, intrahepatic leukocytes were sorted by FACS to index classical mononuclear phagocytes (MNP) defined as Singlets, CD3-CD56-CD19-CD14hiHLA-DR+ or CD14± CD8+T-cells as follows: Singlets, CD3+CD56-CD19-CD4-CD8+V7.2- and split in to CD14± based on an isotype control. Single cells were sorted into 96-well skirted LoBind plates (Eppendorf) containing 5 µL lysis buffer (TCL buffer [Qiagen], supplemented with 1% b-mercaptoethanol [Sigma Aldrich; Merck]) on a BD Bioscience FACSFusion. The sorted plates were subsequently immediately sealed, centrifuged, and placed on dry ice to flash-freeze the cell lysate and stored at -80 'C. \n\nA modified SMART-seq2 protocol57 was performed on the single flow cytometry sorted-cells as previously described58. After cDNA generation, libraries were prepared (384 cells per library) using the Illumina Nextera XT kit (Illumina). Each library was sequenced to achieve a minimum depth of 1-2 million raw reads per cell using an Illumina HiSeq 4000 using v. 4 SBS chemistry to generate 75-bp paired-end reads.","abstract":"Sorted single CD8+T cells expressing CD14 from human liver for SMARTSeq2.\n\nLivers processed: Kucykowicz et al STAR Prot 2022:pubmed.ncbi.nlm.nih.gov/35516846/ \n\nPublished: Pallett et al Nature 2022\nTissue CD14+CD8+T-cells are reprogrammed by myeloid cells and modulated by LPS\n\nThe liver is bathed in bacterial products including LPS transported from the intestinal portal vasculature, but maintains a state of tolerance exploited by persistent pathogens and tumours1,2,3,4. The cellular basis mediating this tolerance, yet allowing a switch to immunity or immunopathology, needs to be better understood for successful immunotherapy of liver diseases. Here we show that a variable proportion of CD8+T-cells compartmentalised in the human liver co-stain for CD14 and other prototypic myeloid membrane proteins; CD14+CD8+T-cells preferentially accumulate within the donor pool in liver allografts, amongst hepatic virus-specific and tumour-infiltrating responses, and in cirrhotic ascites. CD14+CD8+T-cells exhibit increased turnover, activation and constitutive immunomodulatory features with high homeostatic IL-10/IL-2 production directly ex vivo, and an enhanced capacity to rapidly produce antiviral/anti-tumour cytokines upon TCR engagement. This CD14+CD8+T-cell profile can be recapitulated by acquisition of membrane proteins, including the LPS receptor complex, from mononuclear phagocytes, resulting in augmented tumour killing by TCR-redirected T-cells in vitro. CD14+CD8+T-cells express integrins and chemokine receptors favouring interactions with the local stroma, which can promote their induction through CXCL12. LPS can also increase the frequency of CD14+CD8+T-cells in vitro and in vivo, and skew their function towards the production of chemotactic and regenerative cytokines. Thus, bacterial products in the gut-liver axis and tissue stromal factors can tune liver immunity by driving myeloid instruction of CD8+T-cells with immunomodulatory capacity. \n\nFor the analysis of the single cell transcriptome two intrahepatic perfusate samples were isolated and frozen at -80 'C for storage prior to transportation to Newcastle, UK. Once thawed in pre-warmed HBSS containing 0.001% DNaseI, intrahepatic leukocytes were sorted by FACS to index classical mononuclear phagocytes (MNP) defined as Singlets, CD3-CD56-CD19-CD14hiHLA-DR+ or CD14± CD8+T-cells as follows: Singlets, CD3+CD56-CD19-CD4-CD8+V7.2- and split in to CD14± based on an isotype control. Single cells were sorted into 96-well skirted LoBind plates (Eppendorf) containing 5 µL lysis buffer (TCL buffer [Qiagen], supplemented with 1% b-mercaptoethanol [Sigma Aldrich; Merck]) on a BD Bioscience FACSFusion. The sorted plates were subsequently immediately sealed, centrifuged, and placed on dry ice to flash-freeze the cell lysate and stored at -80 'C. \n\nA modified SMART-seq2 protocol57 was performed on the single flow cytometry sorted-cells as previously described58. After cDNA generation, libraries were prepared (384 cells per library) using the Illumina Nextera XT kit (Illumina). Each library was sequenced to achieve a minimum depth of 1-2 million raw reads per cell using an Illumina HiSeq 4000 using v. 4 SBS chemistry to generate 75-bp paired-end reads.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-19T16:14:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006886","title":"One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids","description":"Recent optimization of CRISPR/Cas9-mediated genome engineering has resulted in the development of base editors that can efficiently mediate C&gt;T and A&gt;G transitions. Combining these genome engineering tools with human adult stem cell (ASC)-derived organoid technology holds promise for disease modeling. Here, we demonstrate the application of base editors for the generation of complex tumor models in human ASC-derived hepatocyte, endometrial and intestinal organoids. First, using conventional and evolved Cas9-variants, we show efficacy of both cytosine and adenine base editors and use them to model four hot-spot point mutations in CTNNB1 in hepatocyte organoids. Next, we apply C&gt;T base editors in endometrial organoids to insert nonsense mutations in PTEN and demonstrate tumorigenicity even in the heterozygous state. Furthermore, we use cytosine base editors for simultaneous oncogene activation (PIK3CA) and tumor-suppressor inactivation (APC and TP53). To increase the flexibility of base editor multiplexing, we then combine SpCas9 and SaCas9 base editors for simultaneous C&gt;T and A&gt;G editing at individual target sites. Finally, we show the power of base editor multiplexing by modeling colorectal tumorigenesis in a single step by simultaneously transfecting sgRNA’s targeting four cancer genes.\n\nSeven clonal organoid lines and one bulk wild-type control sample were paired-end whole-genome sequenced using the Illumina Novaseq 6000 system. We sequenced four clonal intestinal organoid lines harbouring engineered TP53 and FBXW7 mutations as well as three lines targeted for oncogenic APC/TP53/PIK3CA/SMAD4 mutations. This WGS showed, as previously reported, a genome-wide increase in C&gt;T mutations due to C&gt;T base editor off-target activity, which is not enriched in predicted off-target regions based on the sgRNA sequences. Furthermore, we confirmed the absence of editing-induced driver mutations and lack of off-target mutational hotspots created by the genomic engineering.","abstract":"Recent optimization of CRISPR/Cas9-mediated genome engineering has resulted in the development of base editors that can efficiently mediate C&gt;T and A&gt;G transitions. Combining these genome engineering tools with human adult stem cell (ASC)-derived organoid technology holds promise for disease modeling. Here, we demonstrate the application of base editors for the generation of complex tumor models in human ASC-derived hepatocyte, endometrial and intestinal organoids. First, using conventional and evolved Cas9-variants, we show efficacy of both cytosine and adenine base editors and use them to model four hot-spot point mutations in CTNNB1 in hepatocyte organoids. Next, we apply C&gt;T base editors in endometrial organoids to insert nonsense mutations in PTEN and demonstrate tumorigenicity even in the heterozygous state. Furthermore, we use cytosine base editors for simultaneous oncogene activation (PIK3CA) and tumor-suppressor inactivation (APC and TP53). To increase the flexibility of base editor multiplexing, we then combine SpCas9 and SaCas9 base editors for simultaneous C&gt;T and A&gt;G editing at individual target sites. Finally, we show the power of base editor multiplexing by modeling colorectal tumorigenesis in a single step by simultaneously transfecting sgRNA’s targeting four cancer genes.\n\nSeven clonal organoid lines and one bulk wild-type control sample were paired-end whole-genome sequenced using the Illumina Novaseq 6000 system. We sequenced four clonal intestinal organoid lines harbouring engineered TP53 and FBXW7 mutations as well as three lines targeted for oncogenic APC/TP53/PIK3CA/SMAD4 mutations. This WGS showed, as previously reported, a genome-wide increase in C&gt;T mutations due to C&gt;T base editor off-target activity, which is not enriched in predicted off-target regions based on the sgRNA sequences. Furthermore, we confirmed the absence of editing-induced driver mutations and lack of off-target mutational hotspots created by the genomic engineering.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-20T13:40:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006887","title":"Chronic lymphocytic leukemia IGHV somatic hypermutation detection by targeted capture next-generation sequencing","description":"Somatic hypermutation (SHM) status of the immunoglobulin heavy variable (IGHV) gene locus plays a crucial role in determining the prognosis and treatment of patients with chronic lymphocytic leukemia (CLL). A common approach for determining SHM status is multiplex PCR of the IGH gene followed by Sanger sequencing; however, this technique is low throughput, vulnerable to failure, and does not allow multiplexing with other molecular diagnostic assays. Here we designed and validated a DNA targeted capture approach that allows the assessment of IGHV SHM status as a sub-module of a larger next-generation sequencing (NGS) assay. We developed an end-to-end assay that takes as input raw FASTQ files and outputs a report containing IGHV SHM status and V-allele usage following the guidelines of the European Research Initiative on CLL (ERIC). We validated the approach on 35 CLL patient samples, 34 of which were previously characterized using Sanger sequencing. The targeted capture NGS panel identified the SHM status of 34 of 35 CLL patients. We showed 100% sensitivity and specificity among the 33 CLL samples with both NGS and Sanger calls. Furthermore, we demonstrated that this panel can be combined with additional targeted capture panels to detect common and prognostically important CLL single nucleotide variants (SNV) and insertion/deletion (indel) variants as well as copy number variants (del17p). Thus, a targeted capture approach to IGHV SHM detection can be easily integrated into broader sequencing panels, allowing broad CLL prognostication in a single molecular assay.","abstract":"Somatic hypermutation (SHM) status of the immunoglobulin heavy variable (IGHV) gene locus plays a crucial role in determining the prognosis and treatment of patients with chronic lymphocytic leukemia (CLL). A common approach for determining SHM status is multiplex PCR of the IGH gene followed by Sanger sequencing; however, this technique is low throughput, vulnerable to failure, and does not allow multiplexing with other molecular diagnostic assays. Here we designed and validated a DNA targeted capture approach that allows the assessment of IGHV SHM status as a sub-module of a larger next-generation sequencing (NGS) assay. We developed an end-to-end assay that takes as input raw FASTQ files and outputs a report containing IGHV SHM status and V-allele usage following the guidelines of the European Research Initiative on CLL (ERIC). We validated the approach on 35 CLL patient samples, 34 of which were previously characterized using Sanger sequencing. The targeted capture NGS panel identified the SHM status of 34 of 35 CLL patients. We showed 100% sensitivity and specificity among the 33 CLL samples with both NGS and Sanger calls. Furthermore, we demonstrated that this panel can be combined with additional targeted capture panels to detect common and prognostically important CLL single nucleotide variants (SNV) and insertion/deletion (indel) variants as well as copy number variants (del17p). Thus, a targeted capture approach to IGHV SHM detection can be easily integrated into broader sequencing panels, allowing broad CLL prognostication in a single molecular assay.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-20T22:05:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006888","title":"GWAS study on multiple sclerosis","description":null,"abstract":"This is a genome wide association study (GWAS) of disease progression in multiple sclerosis (MS). The study involved a total of 12584 cases recruited from multiple centres around the world and tested at 7.8 million common autosomal single nucleotide variants. The data from the European cases (n=4853) are included in this EGA submission in 10 country specific data sub-sets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006889","title":"Whole genome sequencing of microcephaly and primordial dwarfism","description":null,"abstract":"Whole genome sequencing of families with microcephaly and primordial dwarfism. 273 samples including probands and unaffected family members.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006890","title":"Genomic_profiling_of_ALL__TGS","description":"Targeted sequencing of up to 1500 Adult ALL diagnosis samples","abstract":"Targeted sequencing of up to 1500 Adult ALL diagnosis samples","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006891","title":"Targeted_NanoSeq__Aneurysm_","description":"Targeted NanoSeq in vascular aneurysm samples from a number of donors to explore the role of somatic mutations. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape in vascular aneurysms.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006892","title":"Targeted_NanoSeq__Kidney_","description":"Targeted NanoSeq in kidney samples from a number of donors to explore the role of somatic mutations. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape in kidneys.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006893","title":"MASH","description":"MASH","abstract":"MASH","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006894","title":"Tracing early predictors of glioma evolution under therapy","description":"Clonal evolution drives cancer progression and therapeutic resistance. Recent studies revealed divergent longitudinal trajectories in gliomas, but early molecular traits steering post-treatment cancer evolution remain unclear. We analyzed sequencing data of 544 initial-recurrent adult diffuse glioma pairs to identify genomic and transcriptomic early predictors of tumor evolution in each molecular subtype.","abstract":"Clonal evolution drives cancer progression and therapeutic resistance. Recent studies revealed divergent longitudinal trajectories in gliomas, but early molecular traits steering post-treatment cancer evolution remain unclear. We analyzed sequencing data of 544 initial-recurrent adult diffuse glioma pairs to identify genomic and transcriptomic early predictors of tumor evolution in each molecular subtype.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-22T01:52:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006895","title":"Familial pulmonary fibrosis associated with telomere dysfunction and a variant affecting function of NAF1 gene","description":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is a rare progressive scarring lung disease with poor prognosis. TERT and TERC gene mutations are the most common genetic defects in monogenic forms of IPF, despite a genetic cause cannot be established in up to 70% of these cases. To identify the causes of IPF in a Spanish family, we performed whole-exome sequencing and measured telomere shortening (TS). We found TS and multisystem involvement in different members. A novel likely pathogenic mutation predicting a premature stop codon in NAF1 gene was identified in one affected member, while genetic anticipation with TS was observed in non-carriers.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006896","title":"Determining_the_mutation_burden_in_distinct_histological_regions_of_the_proximal_airway__Duplex_","description":"This study aims to determine accurate mutation burdens and signatures in distinct histological regions of the proximal airway of the lung. For this purpose, laser-capture microdissected tissue regions, including submucosal glands, ducts and bronchial epithelium from individuals with different smoking histories will be utilised as an input for nanorate sequencing. This work is directly following up on work published by Yoshida and colleagues (https://www.nature.com/articles/s41586-020-1961-1/).","abstract":"This study aims to determine accurate mutation burdens and signatures in distinct histological regions of the proximal airway of the lung. For this purpose, laser-capture microdissected tissue regions, including submucosal glands, ducts and bronchial epithelium from individuals with different smoking histories will be utilised as an input for nanorate sequencing. This work is directly following up on work published by Yoshida and colleagues (https://www.nature.com/articles/s41586-020-1961-1/).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006897","title":"Determining_the_mutation_burden_in_non_invasive_lung_samples__Duplex_","description":"This study aims to characterize the mutational landscape of non-invasive lung samples, including nasal, laryngeal, as well as trachea samples using whole-genome Nanorate sequencing. In particular, we are interested in determining accurate mutation burdens and signatures in patients with extensive smoking history. The data generated here will be utilised for follow-up in vitro assays for assessing the immunogenicity of bronchial epithelium clones.","abstract":"This study aims to characterize the mutational landscape of non-invasive lung samples, including nasal, laryngeal, as well as trachea samples using whole-genome Nanorate sequencing. In particular, we are interested in determining accurate mutation burdens and signatures in patients with extensive smoking history. The data generated here will be utilised for follow-up in vitro assays for assessing the immunogenicity of bronchial epithelium clones.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006898","title":"Non-viral precision T cell receptor replacement for personalized cell therapy","description":"The T cell receptor (TCR) provides the fine specificity of T cells to recognize mutations in cancer cells 1-3. We developed a clinical-grade approach based on CRISPR/Cas9 non-viral precision genome editing to simultaneously knock-out the two endogenous TCR genes, TCRα (TRAC) and TCRβ (TRBC), and insert in the TRAC locus the two chains of a neoantigen-specific TCR (neoTCR), isolated from the patient’s own circulating T cells using a personalized library of soluble predicted neoantigen-HLA capture reagents. Sixteen patients with refractory solid cancers received up to three distinct neoTCR-transgenic cell products, each expressing a patient-specific neoTCR, in a cell dose-escalation, first-in-human phase 1 clinical trial (NCT03970382). One patient had grade 1 cytokine release syndrome, and one grade 3 encephalitis. All had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease, and the other 11 had disease progression as best response on therapy. NeoTCR-transgenic T cells were detected in tumour biopsies post-infusion at frequencies higher than the native TCRs pre-infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs recognizing mutational neoantigens, the simultaneous knock-out of the endogenous TCR and knock-in of the neoTCRs using single-step, non-viral precision genome editing, the manufacturing of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene edited neoTCR T cell products, and the ability of the transgenic T cells to traffic to the patients’ tumours.","abstract":"The T cell receptor (TCR) provides the fine specificity of T cells to recognize mutations in cancer cells 1-3. We developed a clinical-grade approach based on CRISPR/Cas9 non-viral precision genome editing to simultaneously knock-out the two endogenous TCR genes, TCRα (TRAC) and TCRβ (TRBC), and insert in the TRAC locus the two chains of a neoantigen-specific TCR (neoTCR), isolated from the patient’s own circulating T cells using a personalized library of soluble predicted neoantigen-HLA capture reagents. Sixteen patients with refractory solid cancers received up to three distinct neoTCR-transgenic cell products, each expressing a patient-specific neoTCR, in a cell dose-escalation, first-in-human phase 1 clinical trial (NCT03970382). One patient had grade 1 cytokine release syndrome, and one grade 3 encephalitis. All had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease, and the other 11 had disease progression as best response on therapy. NeoTCR-transgenic T cells were detected in tumour biopsies post-infusion at frequencies higher than the native TCRs pre-infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs recognizing mutational neoantigens, the simultaneous knock-out of the endogenous TCR and knock-in of the neoTCRs using single-step, non-viral precision genome editing, the manufacturing of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene edited neoTCR T cell products, and the ability of the transgenic T cells to traffic to the patients’ tumours.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-22T16:58:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006899","title":"Fetal Alcohol Spectrum Disorder (FASD) Genome-wide Gene Expression","description":null,"abstract":"Fetal alcohol syndrome (FAS) encompasses the mental and physical deficiencies in children of mothers who were exposed to alcohol during pregnancy. We previously identified differences in DNA methylation associated with FAS subphenotypes. To investigate whether the previously identified differences in DNA methylation were associated with differences in expression, we examined the gene expression levels from peripheral blood in the current study obtained from the same cohort as described in Cobben et al. 2019.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006900","title":"Dynamic multilayer-omics analysis in insect venom-anaphylactic patients","description":null,"abstract":"Allergen-specific immunotherapy (AIT) is the only curative option for allergic diseases. However, with the exception of insect-venom AIT, allergy cure still remains an elusive goal for most patients. We applied a multilayer-omics approach to simultaneously reveal the early-stage peripheral immune and gut microbiota landscape in venom-allergy patients (VAP) versus pollen-allergy patients (PAP) under ultra-rush or conventional up-dosing AIT.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006901","title":"Leukemia sequencing study","description":null,"abstract":"Adult low hypodiploid ALL samples from diagnosis were sequencing using a targeted sequencing approach focusing on recurrent altered genes. Paired remission samples were included to identify pre-leukemic alterations in non tumoral cells.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006902","title":"PD-L1 blockade in combination with carboplatin as immune induction in metastatic lobular breast cancer: the GELATO-trial","description":"Invasive lobular breast cancer (ILC) is the second most common histological breast cancer subtype but published data on trials specific for ILC are so far lacking. Translational research revealed that a subset of ILCs may be immune-related and more sensitive to DNA-damaging agents such as platinum. In murine ILC models, synergy between immune checkpoint blockade and platinum has been observed. Here, we tested this concept in the phase II, GELATO-trial (NCT03147040), in which patients with metastatic ILC were treated with weekly carboplatin (AUC 1.5) as immune induction treatment for 12 weeks and atezolizumab (PD-L1 blockade; every three weeks) from the third week onwards until disease progression. Four out of 23 evaluable patients had a partial response (17%, 95%CI 5-39%) and two patients had stable disease for at least 24 weeks, resulting in a clinical benefit rate of 26% (95%CI 10-48%). Out of these six patients, four patients had triple-negative ILC (TN-ILC). In serial biopsies of metastatic lesions, we observed higher CD8 T-cell infiltration, expression of immune checkpoints, and exhausted T cells upon carboplatin/PD-L1 blockade. This is the first report of a clinical trial specifically for ILC and we demonstrate promising anti-tumor activity of atezolizumab with carboplatin as immune induction, in particular for TN-ILC. While activity of carboplatin/PD-L1 blockade in classical ER+ ILC was limited, our translational data yield important insights for the design of highly needed clinical trials in ILC.","abstract":"Invasive lobular breast cancer (ILC) is the second most common histological breast cancer subtype but published data on trials specific for ILC are so far lacking. Translational research revealed that a subset of ILCs may be immune-related and more sensitive to DNA-damaging agents such as platinum. In murine ILC models, synergy between immune checkpoint blockade and platinum has been observed. Here, we tested this concept in the phase II, GELATO-trial (NCT03147040), in which patients with metastatic ILC were treated with weekly carboplatin (AUC 1.5) as immune induction treatment for 12 weeks and atezolizumab (PD-L1 blockade; every three weeks) from the third week onwards until disease progression. Four out of 23 evaluable patients had a partial response (17%, 95%CI 5-39%) and two patients had stable disease for at least 24 weeks, resulting in a clinical benefit rate of 26% (95%CI 10-48%). Out of these six patients, four patients had triple-negative ILC (TN-ILC). In serial biopsies of metastatic lesions, we observed higher CD8 T-cell infiltration, expression of immune checkpoints, and exhausted T cells upon carboplatin/PD-L1 blockade. This is the first report of a clinical trial specifically for ILC and we demonstrate promising anti-tumor activity of atezolizumab with carboplatin as immune induction, in particular for TN-ILC. While activity of carboplatin/PD-L1 blockade in classical ER+ ILC was limited, our translational data yield important insights for the design of highly needed clinical trials in ILC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-24T21:56:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006903","title":"Tracking the evolution of Therapy-Related Myeloid Neoplasms using chemotherapy signatures","description":"Patients treated with cytotoxic therapies, including autologous stem cell transplantation, are at risk for developing therapy-related myeloid neoplasms (tMN). Pre-leukemic clones (i.e., clonal hematopoiesis; CH) are detectable years before the development of these aggressive malignancies, though the genomic events leading to transformation and expansion are not well-defined. Here, leveraging distinctive chemotherapy-associated mutational signatures from whole-genome sequencing data and targeted sequencing of pre-chemotherapy samples, we reconstruct the evolutionary life-history of 39 therapy-related myeloid malignancies. A dichotomy is revealed, in which neoplasms with evidence of chemotherapy-induced mutagenesis from platinum and melphalan are hypermutated and enriched for complex structural variants (i.e., chromothripsis) while neoplasms with non-mutagenic chemotherapy exposures are genomically similar to de novo acute myeloid leukemia. Using chemotherapy-associated mutational signatures as temporal barcodes linked to a discrete clinical exposure in each patient’s life, we estimate that several complex events and genomic drivers are acquired after chemotherapy is administered. For patients with prior multiple myeloma who were treated with high-dose melphalan and autologous stem cell transplantation, we demonstrate that tMN can develop from either a reinfused CH clone that escapes chemotherapy exposure and is selected following reinfusion, or from TP53-mutant CH that survives direct myeloablative conditioning and acquires melphalan-induced DNA-damage. Overall, we reveal a novel mode of tMN progression that is not reliant on direct mutagenesis or even exposure to chemotherapy. Conversely, for tMN that evolve under the influence of chemotherapy-induced mutagenesis, distinct chemotherapies not only select pre-existing CH, but also promote the acquisition of recurrent genomic drivers.","abstract":"Patients treated with cytotoxic therapies, including autologous stem cell transplantation, are at risk for developing therapy-related myeloid neoplasms (tMN). Pre-leukemic clones (i.e., clonal hematopoiesis; CH) are detectable years before the development of these aggressive malignancies, though the genomic events leading to transformation and expansion are not well-defined. Here, leveraging distinctive chemotherapy-associated mutational signatures from whole-genome sequencing data and targeted sequencing of pre-chemotherapy samples, we reconstruct the evolutionary life-history of 39 therapy-related myeloid malignancies. A dichotomy is revealed, in which neoplasms with evidence of chemotherapy-induced mutagenesis from platinum and melphalan are hypermutated and enriched for complex structural variants (i.e., chromothripsis) while neoplasms with non-mutagenic chemotherapy exposures are genomically similar to de novo acute myeloid leukemia. Using chemotherapy-associated mutational signatures as temporal barcodes linked to a discrete clinical exposure in each patient’s life, we estimate that several complex events and genomic drivers are acquired after chemotherapy is administered. For patients with prior multiple myeloma who were treated with high-dose melphalan and autologous stem cell transplantation, we demonstrate that tMN can develop from either a reinfused CH clone that escapes chemotherapy exposure and is selected following reinfusion, or from TP53-mutant CH that survives direct myeloablative conditioning and acquires melphalan-induced DNA-damage. Overall, we reveal a novel mode of tMN progression that is not reliant on direct mutagenesis or even exposure to chemotherapy. Conversely, for tMN that evolve under the influence of chemotherapy-induced mutagenesis, distinct chemotherapies not only select pre-existing CH, but also promote the acquisition of recurrent genomic drivers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2022-12-26T20:00:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006904","title":"Separation of chronic myeloid leukemia stem cells from normal hematopoietic stem cells at single-cell resolution","description":"Chronic myeloid leukemia (CML) is a clonal disease, initiated and sustained by a subpopulation of CML stem cells (CML-SC) containing the BCR::ABL1 oncogene. Genetic markers that enrich for CML-SC have been identified, including CD26 being most specific. Genome sequencing analysis remain yet to be performed at single cell level in order to determine differences and heterogeneity in the genetic profile of CML-SC versus normal hematopoietic stem cells (HSC). Here we show that CD26 and CD33 separate CML-SC from normal HSC in freshly isolated bone marrow samples from newly diagnosed CML patients. DNA sequencing confirms that single CML-SC derived colonies are positive for BCR::ABL1 and harbor a recurrent set of patient-specific clonal somatic mutations across different CML-SC derived colonies. In contrast, marker-negative (CD26-CD33-) HSC from the same patients are negative for the BCR::ABL1 oncogene and do not carry recurrent, clonal mutation across different colonies. These results support the concept that CD26/CD33 expression separates genetically defined, clonal mutant CML-SC from normal HSC that carry individual sets of random mutations in CML patients.\nWe provide whole exome DNA sequencing data for 23 clinical samples of CML-SC plus two buccal swipes derived normal samples. CML samples are comprised of 4 to 8 replicates from two patients, at diagnosis and after treatment. Single CML stem cells before treatment and single non-transformed HSC at remission were selected from bone marrow samples by FACS, according to genetic markers CD33+CD26+ at diagnosis and CD33+CD26-/CD33-CD26- at remission. WES libraries of colony forming assays derived CML-SC and HSC populations were prepared using Agilent SureSelect Human All Exon V6 kit and sequenced running 150 cycles (2x 75bp paired-end) on an Illumina NextSeq 500 platform. Following GATK best practices for somatic mutation calling, novel CML variants and random mutation events during remission phase were obtained.","abstract":"Chronic myeloid leukemia (CML) is a clonal disease, initiated and sustained by a subpopulation of CML stem cells (CML-SC) containing the BCR::ABL1 oncogene. Genetic markers that enrich for CML-SC have been identified, including CD26 being most specific. Genome sequencing analysis remain yet to be performed at single cell level in order to determine differences and heterogeneity in the genetic profile of CML-SC versus normal hematopoietic stem cells (HSC). Here we show that CD26 and CD33 separate CML-SC from normal HSC in freshly isolated bone marrow samples from newly diagnosed CML patients. DNA sequencing confirms that single CML-SC derived colonies are positive for BCR::ABL1 and harbor a recurrent set of patient-specific clonal somatic mutations across different CML-SC derived colonies. In contrast, marker-negative (CD26-CD33-) HSC from the same patients are negative for the BCR::ABL1 oncogene and do not carry recurrent, clonal mutation across different colonies. These results support the concept that CD26/CD33 expression separates genetically defined, clonal mutant CML-SC from normal HSC that carry individual sets of random mutations in CML patients.\nWe provide whole exome DNA sequencing data for 23 clinical samples of CML-SC plus two buccal swipes derived normal samples. CML samples are comprised of 4 to 8 replicates from two patients, at diagnosis and after treatment. Single CML stem cells before treatment and single non-transformed HSC at remission were selected from bone marrow samples by FACS, according to genetic markers CD33+CD26+ at diagnosis and CD33+CD26-/CD33-CD26- at remission. WES libraries of colony forming assays derived CML-SC and HSC populations were prepared using Agilent SureSelect Human All Exon V6 kit and sequenced running 150 cycles (2x 75bp paired-end) on an Illumina NextSeq 500 platform. Following GATK best practices for somatic mutation calling, novel CML variants and random mutation events during remission phase were obtained.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-03T09:29:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006905","title":"Mechanism of action and resistance to Trastuzumab Deruxtecan in patients with metastatic breast cancer: the DAISY trial","description":null,"abstract":"Trastuzumab deruxtecan (T-DXd) is an anti-HER2 (human epidermal growth factor receptor 2) antibody-drug conjugate which has previously shown efficacy in patients with HER2-overexpressing and HER2-low metastatic breast cancer (mBC).  However, the mechanisms of action and resistance of this drug remain partially unclear. DAISY (NCT04132960) is a phase II, open-label study that included patients with mBC whose disease progressed after at least one line of chemotherapy in the metastatic setting. Patients were enrolled in three cohorts according to HER2 expression determined by immunohistochemistry (IHC); cohort 1: HER2-overexpressing (HER2 IHC 3+ or HER2 IHC 2+/ISH+, n=72), cohort 2: HER2-low (HER2 IHC2+/ISH- or HER2 IHC 1+, n=74), and cohort 3: HER2 IHC 0 mBC (n=40). Patients were treated with T-DXd 5.4 mg/kg every 3 weeks until disease progression or unacceptable toxicity. In the full analysis set population (n=177), the confirmed objective response rate (ORR) was of 70.6% (95% CI: 58.3-81) in cohort 1, 37.5% (95% CI: 26.4-49.7) in cohort 2, and 29.7% (95% CI: 15.9-47) in cohort 3 (p &lt;0.0001).  The median progression-free survival (PFS) was 11.1 months (95% CI: 8.5-14.4) in cohort 1, 6.7 months (95% CI: 4.4-8.3) in cohort 2, and 4.2 months (95% CI: 2-5.7); in cohort 3. Cohort 1 was significantly associated with longer PFS (adjusted HR: 0.53, 95% IC: 0.34-0.84, p=0.007), and cohort 3 with shorter PFS (adjusted HR: 1.96, 95% IC: 1.21-3.15, p=0.006) as compared to cohort 2. Exploratory analyses showed that HER2 spatial distribution predicted T-DXd response in patients with HER2-overexpressing mBC and that the transcriptomic response to T-DXd was different according to HER2 expression. No quantitative modulation of tumor microenvironment was observed after 6 to 8 weeks of treatment. Finally, recurrent mutations of the DNA repair gene SLX4 were identified in 20% of samples at resistance (4/20) as compared to 2% in baseline samples (2/88), suggesting that SLX4 mutations could mediate secondary resistance to T-DXd. These data suggest that HER2 is a key determinant of T-DXd efficacy. However, an antitumor activity is also observed in a subgroup of patients without detectable HER2 expression and resistance could be partially mediated by payload sensitivity.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-04T14:26:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006906","title":"Genetic landscape of ENKTCL","description":null,"abstract":"Whole-exome sequencing (WES) data of tumor-normal pairs from 40 ENKTCL patients and RNA sequencing (RNA-seq) data of tumors from 20 ENKTCL patients and genetically manipulated cell line (MSN overexpression) and mouse model (MSN conventional knockout) for functional analysis of MSN.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-04T14:43:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006907","title":"germline variants in children with hematological cancer","description":"Trio parent-child whole exome sequencing has been used to identify cancer predisposing syndrome (CPS) in our pediatric patients with hematological cancer, and it was identified in 3.8%  of the total number of patients(131).","abstract":"Trio parent-child whole exome sequencing has been used to identify cancer predisposing syndrome (CPS) in our pediatric patients with hematological cancer, and it was identified in 3.8%  of the total number of patients(131).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-04T23:34:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006908","title":"IACS treatment on breast cancer bone metastases","description":"Off-target effect of IACS on breast cancer bone metastases.","abstract":"Off-target effect of IACS on breast cancer bone metastases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-05T12:01:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006909","title":"Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection","description":"SARS-CoV-2 vaccine immunogenicity varies between individuals, and immune responses correlate with vaccine efficacy. Using data from 1,076 participants enrolled in ChAdOx1 nCov-19 vaccine efficacy trials in the United Kingdom, we find that inter-individual variation in normalised antibody responses against SARS-CoV-2 spike (S) and its receptor binding domain (RBD) at 28 days following first vaccination   shows genome-wide significant association with major histocompatibility complex (MHC) class II alleles. The most statistically significant association with higher levels of anti-RBD antibody was HLA-DQB1*06 (P=3.2 x 10-9), which we replicate in 1,677 additional vaccinees. Individuals carrying HLA-DQB1*06 alleles were less likely to experience PCR-confirmed breakthrough infection during the Wuhan and Alpha-variant waves compared to non-carriers (HR 0.63, 0.42-0.93, P=0.02). We identify a distinct S-derived peptide that is predicted to bind effectively to HLA-DQB1*06 compared to other equivalent alleles, and find evidence of increased spike-specific memory B-cell responses in HLA-DQB1*06 carriers at 84 days post first vaccination. Our results demonstrate association of HLA type with COVID-19 vaccine antibody response and risk of breakthrough infection, with implications for future vaccine design and implementation.","abstract":"SARS-CoV-2 vaccine immunogenicity varies between individuals, and immune responses correlate with vaccine efficacy. Using data from 1,076 participants enrolled in ChAdOx1 nCov-19 vaccine efficacy trials in the United Kingdom, we find that inter-individual variation in normalised antibody responses against SARS-CoV-2 spike (S) and its receptor binding domain (RBD) at 28 days following first vaccination   shows genome-wide significant association with major histocompatibility complex (MHC) class II alleles. The most statistically significant association with higher levels of anti-RBD antibody was HLA-DQB1*06 (P=3.2 x 10-9), which we replicate in 1,677 additional vaccinees. Individuals carrying HLA-DQB1*06 alleles were less likely to experience PCR-confirmed breakthrough infection during the Wuhan and Alpha-variant waves compared to non-carriers (HR 0.63, 0.42-0.93, P=0.02). We identify a distinct S-derived peptide that is predicted to bind effectively to HLA-DQB1*06 compared to other equivalent alleles, and find evidence of increased spike-specific memory B-cell responses in HLA-DQB1*06 carriers at 84 days post first vaccination. Our results demonstrate association of HLA type with COVID-19 vaccine antibody response and risk of breakthrough infection, with implications for future vaccine design and implementation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-06T03:55:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006910","title":"Whole Exome and RNA sequencing of synchronous female bilateral breast cancers","description":null,"abstract":"Synchronous bilateral breast cancer (sBBC) occurs after both breasts have been affected by the same germline genetics and environmental exposures.  For a genome-scale molecular characterization of sBBC, we performed tumor-normal whole exome sequencing (WES) and tumor RNAseq on a cohort of 6 patients with sBBC who were treated with neoadjuvant chemotherapy (NAC), including pre-NAC samples and post-NAC samples when there was residual disease.  We also performed tumor-normal WES on a validation cohort of 7 patients with sBBC treated with front-line surgery.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-06T14:37:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006911","title":"The genomic diversity of Taiwanese Austronesian groups: implications for the ‘Into and Out of Taiwan’ models","description":null,"abstract":"The origin and dispersal of the Austronesian language family, one of the largest and most widespread in the world, have long attracted the attention of linguists, archaeologists, and geneticists. Even though there is a growing consensus that Taiwan is the source of the spread of Austronesian languages, little is known about the migration patterns of the early Austronesians who settled in and left Taiwan, i.e., the “Into-Taiwan” and “Out-of-Taiwan” events. In particular, the genetic diversity/structure within Taiwan and how this relates to the Into/Out-of-Taiwan events is largely unexplored, because most genomic studies have largely utilized data from just two of the 16 recognized highland Austronesian groups in Taiwan. In this study, we generated the largest genome-wide dataset for Taiwanese Austronesians to date, including six highland groups and one lowland group from across the island, and two Taiwanese Han groups. We identified fine scale genomic structure in Taiwan, inferred the ancestry profile of the ancestors of Austronesians, and found that the southern Taiwanese Austronesians show excess genetic affinities toward the Austronesians outside of Taiwan. Our findings thus shed new light on the Into and Out-of-Taiwan dispersals.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-06T16:37:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006912","title":"scRNA-seq to analyse the influence of different culture conditions on gene expression of duodenum organoids","description":"      We used scRNA-seq to analyse the influence of different culture conditions, including conventional medium (HOM),\n      an ingredient-reduced culture medium containing only EGF, Noggin and R-spondin (ENR),\n      and ENR with Wnt3A addback (ENR+Wnt3A) on the gene expression of duodenum organoids.\n      \n      For full details of methods please see our associated publication\n      \"Identifying phenotype-genotype-function coupling in 3D organoid imaging using Shape, Appearance and Motion Phenotype Observation Tool (SPOT)\".\n      ","abstract":"      We used scRNA-seq to analyse the influence of different culture conditions, including conventional medium (HOM),\n      an ingredient-reduced culture medium containing only EGF, Noggin and R-spondin (ENR),\n      and ENR with Wnt3A addback (ENR+Wnt3A) on the gene expression of duodenum organoids.\n      \n      For full details of methods please see our associated publication\n      \"Identifying phenotype-genotype-function coupling in 3D organoid imaging using Shape, Appearance and Motion Phenotype Observation Tool (SPOT)\".\n      ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-09T17:35:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006913","title":"Clinical utility of combined low-pass whole genome and targeted sequencing in liquid biopsies for diagnosis and monitoring of pediatric solid tumors","description":"We designed a liquid biopsy (LB) platform employing Low-Pass Whole Genome Sequencing (LP-WGS)\nand targeted sequencing of cell-free (cf) DNA isolated from plasma for detecting genome-wide copy\nnumber alterations and targeted gene fusions in pediatric solid tumors. A total of 143 plasma samples\nwere analyzed from 19 controls (patients with non-oncologic diagnoses) and 73 patients, including 44\nwith bone or soft tissue sarcomas, 12 with renal tumors, 10 with germ cell tumors, 5 with hepatic\ntumors, and 2 with thyroid tumors.","abstract":"We designed a liquid biopsy (LB) platform employing Low-Pass Whole Genome Sequencing (LP-WGS)\nand targeted sequencing of cell-free (cf) DNA isolated from plasma for detecting genome-wide copy\nnumber alterations and targeted gene fusions in pediatric solid tumors. A total of 143 plasma samples\nwere analyzed from 19 controls (patients with non-oncologic diagnoses) and 73 patients, including 44\nwith bone or soft tissue sarcomas, 12 with renal tumors, 10 with germ cell tumors, 5 with hepatic\ntumors, and 2 with thyroid tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-09T19:52:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006914","title":"transcriptome analysis of NK cells sorted from PBMCs at baseline and after addition of a T cell dependent bispecific antibody (TDB)","description":null,"abstract":"We found that treatment with the TDB mosunetuzumab in patients resulted in natural killer (NK) cell activation in the peripheral blood. We modeled this phenomenon using PBMCs in vitro and found that TDB-mediated killing activated NK cells, increasing natural killing and antibody dependent cytotoxic (ADCC) function. To define TDB-mediated NK cell activation, we sorted NK cells from PBMCs at baseline and after TDB treatment and performed RNAseq.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-09T20:31:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006915","title":"The University of Hong Kong Gastric Cancer Drug Treatment Study","description":"Targetable drivers governing to 5-fluorouracil and cisplatin (5FU+CDDP) resistance remain elusive due to the paucity of physiologically and therapeutically relevant models. Accordingly, we established 5FU+CDDP resistant intestinal subtype GC patient-derived organoid lines. JAK/STAT signaling and its downstream, adenosine deaminases acting on RNA 1 (ADAR1), are shown to be concomitantly upregulated in the resistant lines. ADAR1 was demonstrated to confer chemoresistance and self-renewal in an RNA editing-dependent manner. WES-seq coupled with RNA-seq identified enrichment of hyperedited lipid metabolism genes in the resistant lines. Mechanistically, ADAR1-mediated A-to-I editing on 3’UTR of stearoyl-CoA desaturase (SCD1) increased binding of KH domain-containing, RNA-binding, signal transduction-associated 1 (KHDRBS1), thereby augmenting SCD1 mRNA stability. Consequently, SCD1 facilitates lipid droplet formation to alleviate chemotherapy-induced ER stress and enhances self-renewal through increasing β-catenin expression. Pharmacological inhibition of SCD1 abrogated chemoresistance and tumor-initiating cell frequency. Clinically, high proteomic level of ADAR1 and SCD1, or high SCD1 editing/ADAR1 mRNA signature score predicts a worse prognosis. Together, we unveiled a novel actionable target to circumvent chemoresistance.","abstract":"Targetable drivers governing to 5-fluorouracil and cisplatin (5FU+CDDP) resistance remain elusive due to the paucity of physiologically and therapeutically relevant models. Accordingly, we established 5FU+CDDP resistant intestinal subtype GC patient-derived organoid lines. JAK/STAT signaling and its downstream, adenosine deaminases acting on RNA 1 (ADAR1), are shown to be concomitantly upregulated in the resistant lines. ADAR1 was demonstrated to confer chemoresistance and self-renewal in an RNA editing-dependent manner. WES-seq coupled with RNA-seq identified enrichment of hyperedited lipid metabolism genes in the resistant lines. Mechanistically, ADAR1-mediated A-to-I editing on 3’UTR of stearoyl-CoA desaturase (SCD1) increased binding of KH domain-containing, RNA-binding, signal transduction-associated 1 (KHDRBS1), thereby augmenting SCD1 mRNA stability. Consequently, SCD1 facilitates lipid droplet formation to alleviate chemotherapy-induced ER stress and enhances self-renewal through increasing β-catenin expression. Pharmacological inhibition of SCD1 abrogated chemoresistance and tumor-initiating cell frequency. Clinically, high proteomic level of ADAR1 and SCD1, or high SCD1 editing/ADAR1 mRNA signature score predicts a worse prognosis. Together, we unveiled a novel actionable target to circumvent chemoresistance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006916","title":"Vitamin C boosts DNA demethylation in TET2 germline mutation carriers","description":"We recently identified a family with lymphoma predisposition where a heterozygous truncating germline mutation in TET2 segregated with nodular lymphocyte predominant Hodgkin lymphoma.  In a clinical trial of one year, we investigated the effects of oral 1 g/day vitamin C supplementation on DNA methylation by analyzing genome-wide DNA methylation and gene expression patterns from the family members.","abstract":"We recently identified a family with lymphoma predisposition where a heterozygous truncating germline mutation in TET2 segregated with nodular lymphocyte predominant Hodgkin lymphoma.  In a clinical trial of one year, we investigated the effects of oral 1 g/day vitamin C supplementation on DNA methylation by analyzing genome-wide DNA methylation and gene expression patterns from the family members.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-10T05:52:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006917","title":"DERMATLAS__Naevus_sebaceous_WES","description":"IVirtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Naevus sebaceous.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Naevus sebaceous.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006918","title":"DERMATLAS__Naevus_sebaceous_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Naevus sebaceous.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Naevus sebaceous.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006919","title":"Genomic and epigenomic study of Japanese renal cell carcinoma including WGS, RNA-seq, ATAC-seq, and methyl-seq","description":"We performed whole-genomic and transcriptomic sequencing of more than 100 Japanese renal cell carcinoma (RCC) cases, including clear cell RCC, papillary RCC, chromophobe RCC, and TFE3-translocated RCC. In addition, we conducted epigenome sequencing analyses: the assay for transposase-accessible chromatin sequencing (ATAC-seq) and enzymatic methyl sequencing.","abstract":"We performed whole-genomic and transcriptomic sequencing of more than 100 Japanese renal cell carcinoma (RCC) cases, including clear cell RCC, papillary RCC, chromophobe RCC, and TFE3-translocated RCC. In addition, we conducted epigenome sequencing analyses: the assay for transposase-accessible chromatin sequencing (ATAC-seq) and enzymatic methyl sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-12T02:18:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006920","title":"van Hijfte GBM dataset 2022/A (single-nucleus RNA-seq)","description":"van Hijfte GBM dataset 2022/A (single-nucleus RNA-seq)\n\n1x GBM","abstract":"van Hijfte GBM dataset 2022/A (single-nucleus RNA-seq)\n\n1x GBM","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-12T12:48:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006921","title":"WGS of pancreatic cancer organoids","description":null,"abstract":"Whole genome sequencing of pancreatic cancer organoids","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006922","title":"Somatic_mutation_and_clonal_evolution_in_the_pancreas__Twist_exome_","description":"In this study, we aim to characterise the landscape of mutation and clonal selection in the pancreas. The data in this study will be generated by whole-exome sequencing of laser-dissected microbiopsies from the pancreas. The samples utilised in this study will include acini, ducts and islets from transplant donors.","abstract":"In this study, we aim to characterise the landscape of mutation and clonal selection in the pancreas. The data in this study will be generated by whole-exome sequencing of laser-dissected microbiopsies from the pancreas. The samples utilised in this study will include acini, ducts and islets from transplant donors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006923","title":"Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA","description":"These data relate to Abbosh et al 2023 'Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA'. Some patients were included in this work that were excluded from the other TRACERx 421 papers (Frankell et al and Al-bakir et al) often due to exclusion criteria in the TRACERx clinical trial. Reasons include partial contamination with C&gt;A artefact mutational signature (CRUK0480 ,0490) which were included for ctDNA detection analyses using high confidence clonal mutations but not clonality analyses, incomplete resection at primary surgery (CRUK0291, 0234, 0230, 0387, 0622) and a concurrent oesophageal second primary cancer (CRUK0498). The primary tissue exome sequencing for these patients that were used in this study are included in this repository. Deep targeted sequencing of (median 200) tumour specific mutations in plasma for 1069 samples from 198 TRACERx patients are also included. Additional details related to these patients and samples can be found in the supplementary or data repositories from Frankell et al and Abbosh et al.","abstract":"These data relate to Abbosh et al 2023 'Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA'. Some patients were included in this work that were excluded from the other TRACERx 421 papers (Frankell et al and Al-bakir et al) often due to exclusion criteria in the TRACERx clinical trial. Reasons include partial contamination with C&gt;A artefact mutational signature (CRUK0480 ,0490) which were included for ctDNA detection analyses using high confidence clonal mutations but not clonality analyses, incomplete resection at primary surgery (CRUK0291, 0234, 0230, 0387, 0622) and a concurrent oesophageal second primary cancer (CRUK0498). The primary tissue exome sequencing for these patients that were used in this study are included in this repository. Deep targeted sequencing of (median 200) tumour specific mutations in plasma for 1069 samples from 198 TRACERx patients are also included. Additional details related to these patients and samples can be found in the supplementary or data repositories from Frankell et al and Abbosh et al.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-13T10:08:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006924","title":"Genetic Predisposition Determines the Therapeutic Responses in Females with Spontaneous Preterm Birth History","description":"Preterm birth is the leading cause for neonatal mortality and morbidity worldwide, but its molecular etiologies was limitedly documented and the therapeutical development lacked progress. The only medication to date, progesterone, has been reported to result in discordant treatment effectiveness from clinical trials. To stratify the underlying genetics of preterm birth, we harvested peipheral blood from 48 females with preterm birth history, who received \nweekly intramuscular injections of Makena from gestational week 16 to 36 for Whole Genome Sequencing. Our downstream analysis identified a panel of genetic variants with myometrium specific functions that significantly result in inferior therapeutical responses on clinical.","abstract":"Preterm birth is the leading cause for neonatal mortality and morbidity worldwide, but its molecular etiologies was limitedly documented and the therapeutical development lacked progress. The only medication to date, progesterone, has been reported to result in discordant treatment effectiveness from clinical trials. To stratify the underlying genetics of preterm birth, we harvested peipheral blood from 48 females with preterm birth history, who received \nweekly intramuscular injections of Makena from gestational week 16 to 36 for Whole Genome Sequencing. Our downstream analysis identified a panel of genetic variants with myometrium specific functions that significantly result in inferior therapeutical responses on clinical.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006925","title":"The Landscape of N-6 Methyladenosine in Primary Localized Prostate Cancer","description":"Using meRIP-sequencing, we profiled N-6 methyladenosine (m6A) in a cohort of 148 primary prostate cancer samples as part of the Canadian Prostate Cancer Genome Network project (CPC-GENE). Paired-end sequencing of 150 bp reads were mapped to GRCh38.p13 using annotations from gencode.v34.chr_patch_hapl_scaff.annotation.gtf. Peaks were called using MeTPeak, joint peaks were identified and IP reads were quantitated, normalized and adjusted using Input reads to obtain estimates of m6A abundance.","abstract":"Using meRIP-sequencing, we profiled N-6 methyladenosine (m6A) in a cohort of 148 primary prostate cancer samples as part of the Canadian Prostate Cancer Genome Network project (CPC-GENE). Paired-end sequencing of 150 bp reads were mapped to GRCh38.p13 using annotations from gencode.v34.chr_patch_hapl_scaff.annotation.gtf. Peaks were called using MeTPeak, joint peaks were identified and IP reads were quantitated, normalized and adjusted using Input reads to obtain estimates of m6A abundance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-14T05:50:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006926","title":"Blood transcriptome profiling links immunity to disease severity in myotonic dystrophy type 1 (DM1).","description":"The blood transcriptome was examined in relation to disease severity in type I myotonic dystrophy (DM1) patients who participated in the Observational Prolonged Trial In DM1 to Improve QoL- Standards (OPTIMISTIC) study. This sought to a) ascertain if transcriptome changes were associated with increasing disease severity, as measured by the muscle impairment rating scale (MIRS) and b) es-tablish if these changes in mRNA expression and associated biological pathways were also observed in the Dystrophia Myotonica Biomarker Discovery Initiative (DMBDI) microarray dataset in blood (with equivalent MIRS/DMPK repeat length). The changes in gene expression were compared using a number of complementary pathways, gene ontology and upstream regulator analyses, which suggested that symptom severity in DM1 was linked to transcriptomic alterations in innate and adaptive im-munity associated with muscle wasting. Future studies should explore the role of immunity in DM1 in more detail to assess its relevance to DM1.","abstract":"The blood transcriptome was examined in relation to disease severity in type I myotonic dystrophy (DM1) patients who participated in the Observational Prolonged Trial In DM1 to Improve QoL- Standards (OPTIMISTIC) study. This sought to a) ascertain if transcriptome changes were associated with increasing disease severity, as measured by the muscle impairment rating scale (MIRS) and b) es-tablish if these changes in mRNA expression and associated biological pathways were also observed in the Dystrophia Myotonica Biomarker Discovery Initiative (DMBDI) microarray dataset in blood (with equivalent MIRS/DMPK repeat length). The changes in gene expression were compared using a number of complementary pathways, gene ontology and upstream regulator analyses, which suggested that symptom severity in DM1 was linked to transcriptomic alterations in innate and adaptive im-munity associated with muscle wasting. Future studies should explore the role of immunity in DM1 in more detail to assess its relevance to DM1.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-16T16:25:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006927","title":"Genomic profiling of localized (lFL) and systemic follicular lymphoma (sFL) reveals novel insights into FL pathogenesis","description":"At diagnosis, the majority of FL presents with symptomatic disease in advanced/systemic stages of FL (sFL). In contrast only around 10 to 15% of cFL are diagnosed in localized stages (lFL). The biological knowledge is mainly based on data derived from global sFL analysis and only small cohorts of lFL were characterized intensively so far. It is well-known that the hallmark BCL2 translocation is less frequently observed in lFL. Furthermore, lFL differs from sFL concerning their gene expression and their N-glycosylation profiles. In consequence, comprehensive global analysis with CNA profiling and whole exome sequencing was performed in a large cohort of lFL. Additionally, the mutational profile as well as the CNA landscape of lFL and sFL, as well as for BCL2 translocation-positive and  -negative was compared.","abstract":"At diagnosis, the majority of FL presents with symptomatic disease in advanced/systemic stages of FL (sFL). In contrast only around 10 to 15% of cFL are diagnosed in localized stages (lFL). The biological knowledge is mainly based on data derived from global sFL analysis and only small cohorts of lFL were characterized intensively so far. It is well-known that the hallmark BCL2 translocation is less frequently observed in lFL. Furthermore, lFL differs from sFL concerning their gene expression and their N-glycosylation profiles. In consequence, comprehensive global analysis with CNA profiling and whole exome sequencing was performed in a large cohort of lFL. Additionally, the mutational profile as well as the CNA landscape of lFL and sFL, as well as for BCL2 translocation-positive and  -negative was compared.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-17T10:37:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006928","title":"Identifying rare genetic variants in 21 highly multiplex autism families","description":null,"abstract":"Neurodevelopmental conditions with a genetic component, such as autism, are a highly heritable heterogeneous group. Large-scale genetic studies, predominantly focussing on simplex families and clinical diagnoses of autism have identified hundreds of genes associated with autism. Yet, the contribution of these classes of genes to multiplex families and autistic traits still warrants investigation. Here, we conducted whole-genome sequencing of 21 highly multiplex autism families, with at least three autistic individuals in each family, to prioritise genes associated with autism. Using a combination of both autistic traits and clinical diagnosis of autism, we identify rare variants in genes associated with autism, and related neurodevelopmental conditions in multiple families. We identify a modest excess of these variants in autistic individuals compared to individuals without an autism diagnosis. Finally, we identify a convergence of the genes identified in molecular pathways related to development and neurogenesis. In sum, our analysis provides initial evidence to demonstrate the value of integrating autism diagnosis and autistic traits to prioritise genes.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-17T11:07:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006929","title":"CYP2C19 long-read sequencing","description":"Inter-individual differences in drug response based on genetic variations can lead to drug toxicity and treatment inefficacy. A large part of this variability is caused by genetic variants in pharmacogenes. Unfortunately, the Single Nucleotide Variant (SNV) panels currently used in clinical pharmacogenomic (PGx) testing are unable to detect all genetic variability in these genes. Long-read sequencing, on the other hand, has been shown to be able to resolve complex (pharmaco)genes. In this study we have assessed the added value of long-read sequencing for PGx focusing on the clinically important and highly polymorphic CYP2C19 gene. With a capture-based long-read sequencing panel we were able to characterize the entire region and assign variants to their allele of origin (phasing), resulting in the identification of 813 unique variants in 37 samples. To assess the clinical utility of this data we have compared the performance of three different *-allele tools (Aldy, PharmCat and PharmaKU) which are specifically designed to assign clinical haplotypes to pharmacogenes based on all input variants. We conclude that long-read sequencing can improve our ability to characterize the CYP2C19 locus, help to identify novel haplotypes and that *-allele tools are an useful asset in phenotype prediction. Ultimately, this approach could help to better predict an individual’s drug response and improve therapy outcomes.","abstract":"Inter-individual differences in drug response based on genetic variations can lead to drug toxicity and treatment inefficacy. A large part of this variability is caused by genetic variants in pharmacogenes. Unfortunately, the Single Nucleotide Variant (SNV) panels currently used in clinical pharmacogenomic (PGx) testing are unable to detect all genetic variability in these genes. Long-read sequencing, on the other hand, has been shown to be able to resolve complex (pharmaco)genes. In this study we have assessed the added value of long-read sequencing for PGx focusing on the clinically important and highly polymorphic CYP2C19 gene. With a capture-based long-read sequencing panel we were able to characterize the entire region and assign variants to their allele of origin (phasing), resulting in the identification of 813 unique variants in 37 samples. To assess the clinical utility of this data we have compared the performance of three different *-allele tools (Aldy, PharmCat and PharmaKU) which are specifically designed to assign clinical haplotypes to pharmacogenes based on all input variants. We conclude that long-read sequencing can improve our ability to characterize the CYP2C19 locus, help to identify novel haplotypes and that *-allele tools are an useful asset in phenotype prediction. Ultimately, this approach could help to better predict an individual’s drug response and improve therapy outcomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-17T12:04:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006930","title":"Impact_of_radiotherapy_on_DNA_damage_and_repair_in_sarcoma_NanoSeq","description":"Investigation of the impact of radiotherapy on DNA damage and repair in sarcoma by whole-genome NanoSeq.","abstract":"Investigation of the impact of radiotherapy on DNA damage and repair in sarcoma by whole-genome NanoSeq.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006931","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__AA_study_urine","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, head and neck, bladder, gall bladder, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \n\nThis sub-project will specifically investigate aristolochic exposure in Europe.\n\nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, head and neck, bladder, gall bladder, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \n\nThis sub-project will specifically investigate aristolochic exposure in Europe.\n\nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006932","title":"Multiome_HB","description":"Hepatoblastoma (HB) cells display strong phenotypic heterogeneity with a major impact on drug response, but the underlying mechanisms are poorly understood. Here, we use a single-cell multi-omic strategy to unravel the molecular determinants of this plasticity. HB display a continuum of single-cell states between hepatocytic (scH), liver progenitor (scLP) and mesenchymal (scM) differentiation poles, with an intermediate scH/LP population bordering scLP and scH areas in spatial transcriptomics. Chromatin accessibility landscapes reveal the gene regulatory networks of each differentiation pole, and the sequence of transcription factor activation underlying cell state transitions. Single-cell mapping of somatic alterations reveals the clonal architecture of each tumor, showing that each genetic subclone displays its own range of cellular plasticity across differentiation poles. The most scLP subclones, overexpressing stem cell and DNA repair genes, proliferate faster after neo-adjuvant chemotherapy. These results highlight how the interplay of clonal evolution and epigenetic plasticity shapes the potential of HB subclones to respond to chemotherapy.","abstract":"Hepatoblastoma (HB) cells display strong phenotypic heterogeneity with a major impact on drug response, but the underlying mechanisms are poorly understood. Here, we use a single-cell multi-omic strategy to unravel the molecular determinants of this plasticity. HB display a continuum of single-cell states between hepatocytic (scH), liver progenitor (scLP) and mesenchymal (scM) differentiation poles, with an intermediate scH/LP population bordering scLP and scH areas in spatial transcriptomics. Chromatin accessibility landscapes reveal the gene regulatory networks of each differentiation pole, and the sequence of transcription factor activation underlying cell state transitions. Single-cell mapping of somatic alterations reveals the clonal architecture of each tumor, showing that each genetic subclone displays its own range of cellular plasticity across differentiation poles. The most scLP subclones, overexpressing stem cell and DNA repair genes, proliferate faster after neo-adjuvant chemotherapy. These results highlight how the interplay of clonal evolution and epigenetic plasticity shapes the potential of HB subclones to respond to chemotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-17T15:22:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006934","title":"Isala Citizen Science Project: Cross-sectional branch","description":"The Isala Citizen Science Project, is named after the first female doctor in Belgium, Isala Van Diest (1842-1916). In a co-creative way, volunteers provided samples and data, proposed research objectives and survey questions, and helped to disseminate and interpret the objectives and results through different media platforms, jointly breaking taboos on women’s and vaginal health. In Flow 1, we collected a single sample from a cross-section of the population, characterized the microbiome, and associated it with data collected in questionnaires. Here, we provide extensive sample meta-data for over 3000 women who completed questionnaires on their lifestyle, diet, health, contraceptive use and environment.","abstract":"The Isala Citizen Science Project, is named after the first female doctor in Belgium, Isala Van Diest (1842-1916). In a co-creative way, volunteers provided samples and data, proposed research objectives and survey questions, and helped to disseminate and interpret the objectives and results through different media platforms, jointly breaking taboos on women’s and vaginal health. In Flow 1, we collected a single sample from a cross-section of the population, characterized the microbiome, and associated it with data collected in questionnaires. Here, we provide extensive sample meta-data for over 3000 women who completed questionnaires on their lifestyle, diet, health, contraceptive use and environment.","study_type":"Other","pubmed_ids":[34765924],"external_links":null,"is_released":true,"released_date":"2023-01-17T16:12:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006935","title":"Bolleboom-Gao peri-tumoral snRNA-seq glioblastoma dataset 2022/A","description":"Bolleboom-Gao peri-tumoral snRNA-seq glioblastoma dataset 2022/A","abstract":"Bolleboom-Gao peri-tumoral snRNA-seq glioblastoma dataset 2022/A","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-17T19:08:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006936","title":"A machine learning classifier for DNA repair defects using plasma DNA.","description":null,"abstract":"We present DARC Sign (DnA Repair Classification SIGNatures); a public machine learning tool leveraging clinically-practical liquid biopsy specimens for simultaneously identifying multiple types of metastatic prostate cancer DDR deficiencies. We posit that it will be useful for understanding differential responses to DDR-directed therapies in ongoing clinical trials and may ultimately enable prospective identification of prostate cancers with phenotypic evidence of DDR deficiency.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006937","title":"TNBC ctDNA Targeted Panel","description":"Circulating tumour DNA (ctDNA) detection in liquid biopsy is an emerging alternative to tissue biopsy, but its utility in treatment response monitoring and prognosis in triple negative breast cancer (TNBC) remains to be well understood. In this study, we determined the presence of early stage TNBC ctDNA detectable actionable mutations with a clinically validated hotspot treatment indication panel. Sequencing of plasma DNA from 130 TNBC patients collected within 7 months of primary treatment completion revealed that 7.7% had detectable residual disease with a hotspot panel. Among neoadjuvant treated patients, we observed a trend where patients with incomplete pathologic response and positive ctDNA within 7 months of treatment completion were at risk of reduced progression free survival. We propose that a high risk subset of early TNBC patients treated in NAT protocols may be identifiable by combining tissue response and sensitive ctDNA detection.","abstract":"Circulating tumour DNA (ctDNA) detection in liquid biopsy is an emerging alternative to tissue biopsy, but its utility in treatment response monitoring and prognosis in triple negative breast cancer (TNBC) remains to be well understood. In this study, we determined the presence of early stage TNBC ctDNA detectable actionable mutations with a clinically validated hotspot treatment indication panel. Sequencing of plasma DNA from 130 TNBC patients collected within 7 months of primary treatment completion revealed that 7.7% had detectable residual disease with a hotspot panel. Among neoadjuvant treated patients, we observed a trend where patients with incomplete pathologic response and positive ctDNA within 7 months of treatment completion were at risk of reduced progression free survival. We propose that a high risk subset of early TNBC patients treated in NAT protocols may be identifiable by combining tissue response and sensitive ctDNA detection.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-18T20:07:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006938","title":"WTOS_Tumours_Diseased_Behjati_WellcomeCore_Managed_Access","description":"SMARCA4/B1 driven tumours","abstract":"SMARCA4/B1 driven tumours","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006939","title":"Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions(H021/INF)","description":"Many rare cancers are not well understood, and pathogenesis-directed therapies are often lacking, resulting in poor patient outcomes. Leveraging two (inter)national precision oncology trials that enroll large numbers of rare cancers, we investigated the clinical, histopathologic, molecular, and functional characteristics of rhabdomyosarcoma (RMS) with fusions of FUS or EWSR1 to the TFCP2 transcription factor, a recently discovered ultra-rare entity whose classification, pathogenesis, and optimal treatment are unclear. Unusually for fusion-driven sarcomas, most cases had highly rearranged genomes, including chromothripsis, and signs of defective homologous recombination DNA repair. All tumors showed extreme expression of a truncated TERT variant and the ALK receptor tyrosine kinase, which was additionally affected by intragenic deletions and aberrant splicing, resulting in the expression of shortened variants in 58% of cases. Three ALK variants were oncogenic in immortalized cells, and patient-derived tumor cells expressing two variants responded to certain ALK inhibitors. Other recurrent alterations included CDKN2A/MTAP co-deletions and mutations in PAPPA2, encoding an IGFBP5-specific proteinase, in 67% and 25% of cases, respectively. DNA methylation analysis, along with 19 other soft-tissue sarcoma classes, revealed a close relationship with undifferentiated sarcoma but not other RMS subtypes, suggesting that TFCP2-rearranged RMS is a separate entity, possibly arising from a distinct cell of origin. Expression of TFCP2 fusions in immortalized human cells blocked late myogenic differentiation and significantly induced genes that were also highly expressed in patient tumors, including ALK, TERT, and two known regulators of skeletal muscle cells, IGFBP5 and PTH1R. Genome-wide chromatin profiling demonstrated direct binding of FUS-TFCP2 to the ALK and TERT loci outside their regular promoters, which correlated with the expression of alternative transcript variants. Finally, FUS-TFCP2 inhibited the repair of DNA double-strand breaks in immortalized cells, rendering them sensitive to treatment with cisplatin. This study provides insight into the pathogenesis and therapeutic vulnerabilities of a new RMS subtype and illustrates the value of linking comprehensive molecular diagnostics and functional annotation within multicenter consortia to improve the understanding and clinical management of rare cancers.","abstract":"Many rare cancers are not well understood, and pathogenesis-directed therapies are often lacking, resulting in poor patient outcomes. Leveraging two (inter)national precision oncology trials that enroll large numbers of rare cancers, we investigated the clinical, histopathologic, molecular, and functional characteristics of rhabdomyosarcoma (RMS) with fusions of FUS or EWSR1 to the TFCP2 transcription factor, a recently discovered ultra-rare entity whose classification, pathogenesis, and optimal treatment are unclear. Unusually for fusion-driven sarcomas, most cases had highly rearranged genomes, including chromothripsis, and signs of defective homologous recombination DNA repair. All tumors showed extreme expression of a truncated TERT variant and the ALK receptor tyrosine kinase, which was additionally affected by intragenic deletions and aberrant splicing, resulting in the expression of shortened variants in 58% of cases. Three ALK variants were oncogenic in immortalized cells, and patient-derived tumor cells expressing two variants responded to certain ALK inhibitors. Other recurrent alterations included CDKN2A/MTAP co-deletions and mutations in PAPPA2, encoding an IGFBP5-specific proteinase, in 67% and 25% of cases, respectively. DNA methylation analysis, along with 19 other soft-tissue sarcoma classes, revealed a close relationship with undifferentiated sarcoma but not other RMS subtypes, suggesting that TFCP2-rearranged RMS is a separate entity, possibly arising from a distinct cell of origin. Expression of TFCP2 fusions in immortalized human cells blocked late myogenic differentiation and significantly induced genes that were also highly expressed in patient tumors, including ALK, TERT, and two known regulators of skeletal muscle cells, IGFBP5 and PTH1R. Genome-wide chromatin profiling demonstrated direct binding of FUS-TFCP2 to the ALK and TERT loci outside their regular promoters, which correlated with the expression of alternative transcript variants. Finally, FUS-TFCP2 inhibited the repair of DNA double-strand breaks in immortalized cells, rendering them sensitive to treatment with cisplatin. This study provides insight into the pathogenesis and therapeutic vulnerabilities of a new RMS subtype and illustrates the value of linking comprehensive molecular diagnostics and functional annotation within multicenter consortia to improve the understanding and clinical management of rare cancers.","study_type":"Other","pubmed_ids":[38168093],"external_links":null,"is_released":true,"released_date":"2023-01-19T12:40:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006940","title":"Methylation_Landscape_in_Breast","description":"LCM Methylation of healthy and cancerous breast tissue","abstract":"Investigating age-associated methylation patterns in healthy and cancerous breast tissue","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006941","title":"MutWP1__CRUK_Grand_Challenge__RCC_Nanoseq","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006942","title":"Clonal architecture and genomic features of smoking versus non-smoking oncogene-driven East-Asian non-small cell lung cancer","description":"Unlike smoking-related non-small cell lung cancers (NSCLC), oncogene-driven tumors are characterized by low mutational burdens and complex genomic landscapes. However, the clonal architecture and genomic landscape of the oncogene-driven tumors in smokers remains unknown. Here, we investigate the impact of tobacco smoking on the genomic and transcriptomic alterations in the context of oncogene-driven NSCLC.","abstract":"Unlike smoking-related non-small cell lung cancers (NSCLC), oncogene-driven tumors are characterized by low mutational burdens and complex genomic landscapes. However, the clonal architecture and genomic landscape of the oncogene-driven tumors in smokers remains unknown. Here, we investigate the impact of tobacco smoking on the genomic and transcriptomic alterations in the context of oncogene-driven NSCLC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-20T02:27:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006943","title":"SLCas9_JAK2_HT_29_21_12_22","description":"samples from cell pellets that have been processed to purified PCR2 samples using standard Kosuke primers and one DNA plasmid sample.","abstract":"samples from cell pellets that have been processed to purified PCR2 samples using standard Kosuke primers and one DNA plasmid sample.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006944","title":"Genotype data from 'Dense sampling of ethnic groups within African countries reveals fine-scale genetic structure and extensive historical admixture.'","description":"Previous studies have highlighted how African genomes have been shaped by a complex series of historical events. Despite this, genome-wide data has only been obtained from a small proportion of present-day ethnolinguistic groups. By analysing new autosomal genetic variation data of 1333 individuals from over 150 ethnic groups from Cameroon, Republic of the Congo, Ghana, Nigeria and Sudan, we demonstrate a previously underappreciated fine-scale level of\ngenetic structure within these countries, for example correlating with historical polities in western Cameroon. By comparing genetic variation patterns among populations, we infer that many northern Cameroonian and Sudanese groups share genetic links with multiple geographically disparate populations, likely resulting from long-distance migrations. In Ghana and Nigeria, we infer signatures of intermixing dated to over 2000 years ago, corresponding to reports of environmental transformations possibly related to climate change. We also infer recent intermixing signals in multiple African populations, including Congolese, that likely relates to the expansions of Bantu language-speaking peoples.","abstract":"Previous studies have highlighted how African genomes have been shaped by a complex series of historical events. Despite this, genome-wide data has only been obtained from a small proportion of present-day ethnolinguistic groups. By analysing new autosomal genetic variation data of 1333 individuals from over 150 ethnic groups from Cameroon, Republic of the Congo, Ghana, Nigeria and Sudan, we demonstrate a previously underappreciated fine-scale level of\ngenetic structure within these countries, for example correlating with historical polities in western Cameroon. By comparing genetic variation patterns among populations, we infer that many northern Cameroonian and Sudanese groups share genetic links with multiple geographically disparate populations, likely resulting from long-distance migrations. In Ghana and Nigeria, we infer signatures of intermixing dated to over 2000 years ago, corresponding to reports of environmental transformations possibly related to climate change. We also infer recent intermixing signals in multiple African populations, including Congolese, that likely relates to the expansions of Bantu language-speaking peoples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-20T11:29:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006945","title":"Comprehensive epigenomic profiling reveals the extent of disease-specific chromatin states and informs drug target discovery in ankylosing spondylitis","description":"Ankylosing spondylitis (AS) is a common, highly heritable inflammatory arthritis characterised by enthesitis of the spine and sacroiliac joints. Genome-wide association studies have revealed &amp;gt;100 genetic associations but their functional effects remain largely unresolved. Here, we present a comprehensive transcriptomic and epigenomic map of disease-relevant blood immune cell subsets from AS patients and healthy controls. We report differential disease signatures for specific genomic regions from individual -omic modalities and multi-omic integration, showing enrichment at genetically associated loci and evidence for altered monocyte function in AS. We link putative functional SNPs with cognate genes using high-resolution Capture-C at 10 loci, including PTGER4 and ETS1. We also show how disease-specific functional genomic data can be integrated with GWAS evidence to enhance therapeutic target discovery. This study combines multiple epigenetic and transcriptional analysis with GWAS to identify cell types, candidate drug target genes and transcriptional regulation of likely pathogenic relevance.","abstract":"Ankylosing spondylitis (AS) is a common, highly heritable inflammatory arthritis characterised by enthesitis of the spine and sacroiliac joints. Genome-wide association studies have revealed &amp;gt;100 genetic associations but their functional effects remain largely unresolved. Here, we present a comprehensive transcriptomic and epigenomic map of disease-relevant blood immune cell subsets from AS patients and healthy controls. We report differential disease signatures for specific genomic regions from individual -omic modalities and multi-omic integration, showing enrichment at genetically associated loci and evidence for altered monocyte function in AS. We link putative functional SNPs with cognate genes using high-resolution Capture-C at 10 loci, including PTGER4 and ETS1. We also show how disease-specific functional genomic data can be integrated with GWAS evidence to enhance therapeutic target discovery. This study combines multiple epigenetic and transcriptional analysis with GWAS to identify cell types, candidate drug target genes and transcriptional regulation of likely pathogenic relevance.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-20T11:45:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006946","title":"Genomic Analysis of a Metastatic Fusion-negative Embryonal Rhabdomyosarcoma","description":null,"abstract":"Autopsy-derived, later snap-frozen tissue fragments from a 5-year-old female with recurrent metastatic fusion-negative embryonal rhabdomyosarcoma (RMS) primary tumor of the left thigh were analyzed.  No quality matched tissue was available.  Prior panel analysis identified 2 prominent genetic changes:  NRAS Q61K, PIK3CA H1047R, CDKN2A/B loss, and ERBB3 overexpression.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-20T21:41:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006947","title":"Case Report: Rare IKZF1 gene fusions identified in neonate with congenital KMT2A-rearranged Acute Lymphoblastic Leukemia","description":"Here we describe a rare case of congenital KMT2Ar ALL presenting with co-occurring IKZF1 gene fusions and a predictably aggressive disease trajectory. We report for the first time, the novel IKZF1::TUT1 and KDM2A::IKZF1 gene fusions. Rearrangements in-volving KMT2A are commonly retained in relapsed infant ALL, however, in this case the KMT2A::AFF1 gene fusion did not appear to be the lesion driving leukemic relapse. Instead, our data suggest that relapse was driven by IKZF1::TUT1. This gene fusion remained in all samples investigated, including the on-blinatumomab therapy sample taken immediately prior to relapse. Conversely, the KMT2A::AFF1 gene fusion was only detected in the diagnosis and refractory post-induction samples highlighting a key role for IKZF1::TUT1 in disease pathogenesis. Intriguingly, both IKZF1 gene fusions are predicted to be out-of-frame, however, our data demonstrate the IKZF1 gene is still expressed. This is not unprecedented and it has previously been observed that out-of-frame fusions can cause transcriptional activation/repression of genes involved in the fusions leading to increases or decreases of their expression and the as-sociated functional outcomes.","abstract":"Here we describe a rare case of congenital KMT2Ar ALL presenting with co-occurring IKZF1 gene fusions and a predictably aggressive disease trajectory. We report for the first time, the novel IKZF1::TUT1 and KDM2A::IKZF1 gene fusions. Rearrangements in-volving KMT2A are commonly retained in relapsed infant ALL, however, in this case the KMT2A::AFF1 gene fusion did not appear to be the lesion driving leukemic relapse. Instead, our data suggest that relapse was driven by IKZF1::TUT1. This gene fusion remained in all samples investigated, including the on-blinatumomab therapy sample taken immediately prior to relapse. Conversely, the KMT2A::AFF1 gene fusion was only detected in the diagnosis and refractory post-induction samples highlighting a key role for IKZF1::TUT1 in disease pathogenesis. Intriguingly, both IKZF1 gene fusions are predicted to be out-of-frame, however, our data demonstrate the IKZF1 gene is still expressed. This is not unprecedented and it has previously been observed that out-of-frame fusions can cause transcriptional activation/repression of genes involved in the fusions leading to increases or decreases of their expression and the as-sociated functional outcomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-22T01:25:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006948","title":"Blood Transcriptome Profiling Links Immunity to Disease Severity in Myotonic Dystrophy Type 1 (DM1)","description":null,"abstract":"The blood transcriptome was examined in relation to disease severity in type I myotonic dystrophy (DM1) patients who participated in the Observational Prolonged Trial In DM1 to Improve QoL- Standards (OPTIMISTIC) study. This sought to (a) ascertain if transcriptome changes were associated with increasing disease severity, as measured by the muscle impairment rating scale (MIRS), and (b) establish if these changes in mRNA expression and associated biological pathways were also observed in the Dystrophia Myotonica Biomarker Discovery Initiative (DMBDI) microarray dataset in blood (with equivalent MIRS/DMPK repeat length). The changes in gene expression were compared using a number of complementary pathways, gene ontology and upstream regulator analyses, which suggested that symptom severity in DM1 was linked to transcriptomic alterations in innate and adaptive immunity associated with muscle-wasting. Here, we explore the molecular signatures in RNA sequencing data from blood associated with disease severity as measured in DM1 patients with less than 400 CTG-repeat length size in the DMPK gene in blood. These DM1 patients participated in the OPTIMISTIC study. This approach involved stratifying those within the OPTIMISTIC study into different patient groups with different degrees of disease severity (as measured by the muscle-impairment rating scale (MIRS)) and assessed at baseline. Patients were divided into groups with mild (MIRS 1–2) and severe (MIRS 3–5) neuromuscular symptoms with different DMPK repeat length characteristics.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006949","title":"Pre-diagnostic saliva microbiota of Finnish children with autoimmune diseases","description":"Pre-diagnostic saliva microbiota samples of Finnish children (aged 11/12 years). This is a case-control study, where case refers to the children who developed Type 1 DM or IBD later in life and control refers to the children who were free from these diseases. The aim of the study was to find biomarkers in saliva microbiota that may help us predict DM or IBD before the onset of these diseases.","abstract":"Pre-diagnostic saliva microbiota samples of Finnish children (aged 11/12 years). This is a case-control study, where case refers to the children who developed Type 1 DM or IBD later in life and control refers to the children who were free from these diseases. The aim of the study was to find biomarkers in saliva microbiota that may help us predict DM or IBD before the onset of these diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-23T07:41:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006950","title":"Genotype data of Japanese","description":"Genotype data of the Japanese population (N=142) were collected at Osaka University. Genotyping was performed using Infinium Asian Screening Array (Illumina, USA).","abstract":"Genotype data of the Japanese population (N=142) were collected at Osaka University. Genotyping was performed using Infinium Asian Screening Array (Illumina, USA).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-24T05:11:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006951","title":"Lung Adenocarcinoma Promotion by Air Pollutants","description":"A complete understanding of how environmental carcinogenic exposures promote cancer formation is lacking. Over 70 years ago, tumour formation was proposed to occur in a two step process: an initiating step which induces mutations in normal tissue, followed by a promoter step which triggers cancer development. Recent evidence has revealed healthy human tissue contains a patchwork of clones harbouring oncogenic mutations.This led us to hypothesise that environmental particulate matter measuring PM2.5, known to be associated with lung cancer risk, might promote lung cancer by acting on pre-existing cells harbouring oncogenic mutations in normal lung tissue. Here we use a combination of WGS and RNA-seq of mouse tumours from pollution-exposed mice to examine the impact of particulate matter on mutagenesis and gene expression respectively.","abstract":"A complete understanding of how environmental carcinogenic exposures promote cancer formation is lacking. Over 70 years ago, tumour formation was proposed to occur in a two step process: an initiating step which induces mutations in normal tissue, followed by a promoter step which triggers cancer development. Recent evidence has revealed healthy human tissue contains a patchwork of clones harbouring oncogenic mutations.This led us to hypothesise that environmental particulate matter measuring PM2.5, known to be associated with lung cancer risk, might promote lung cancer by acting on pre-existing cells harbouring oncogenic mutations in normal lung tissue. Here we use a combination of WGS and RNA-seq of mouse tumours from pollution-exposed mice to examine the impact of particulate matter on mutagenesis and gene expression respectively.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-24T10:25:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006952","title":"The immunological characterization of expanded tumor-infiltrating lymphocytes in renal cell carcinoma patients","description":"In this study, we comprehensively characterized the non-expanded and expanded tumor-infiltrating lymphocytes (TILs) from treatment-naïve RCC patients, as well as the corresponding “young” TILs (pre-REP TILs) and “rapidly expanded” TILs (REP TILs) following a clinical-grade TIL production protocol. From our scRNA+TCRαβ-seq and TCRβ-seq analyses, we show that the REP protocol preferentially favors the expansion CD4+ T-cells that originate from small T-cell clones in the tumor microenvironment (TME), indicating that the large, exhausted T-cell clones in the tumor do not expand during the protocol. We further identified RCC-associated TCR motifs that were validated in multiple TCRαβ-seq and scRNA+TCRαβ-seq datasets, as well as quantified the RCC-associated TCRs from the REP protocol. Overall, the T-cells carrying the RCC-associated TCRs remained high in the tumors and corresponding pre-REP TILs, but the frequency was reduced in the REP TILs. Furthermore, the overall anti-viral TCRs remained low throughout the REP protocol. Our results provide an in-depth understanding of the origin, phenotype, and specificity of the TCRs in RCC TILs.","abstract":"In this study, we comprehensively characterized the non-expanded and expanded tumor-infiltrating lymphocytes (TILs) from treatment-naïve RCC patients, as well as the corresponding “young” TILs (pre-REP TILs) and “rapidly expanded” TILs (REP TILs) following a clinical-grade TIL production protocol. From our scRNA+TCRαβ-seq and TCRβ-seq analyses, we show that the REP protocol preferentially favors the expansion CD4+ T-cells that originate from small T-cell clones in the tumor microenvironment (TME), indicating that the large, exhausted T-cell clones in the tumor do not expand during the protocol. We further identified RCC-associated TCR motifs that were validated in multiple TCRαβ-seq and scRNA+TCRαβ-seq datasets, as well as quantified the RCC-associated TCRs from the REP protocol. Overall, the T-cells carrying the RCC-associated TCRs remained high in the tumors and corresponding pre-REP TILs, but the frequency was reduced in the REP TILs. Furthermore, the overall anti-viral TCRs remained low throughout the REP protocol. Our results provide an in-depth understanding of the origin, phenotype, and specificity of the TCRs in RCC TILs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-24T14:54:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006953","title":"Clonal B-cell expansions preceding multiple myeloma may affect treatment monitoring","description":null,"abstract":"The cell of origin and pathogenesis of multiple myeloma (MM) remains controversial. Here, we used single-cell and bulk sequencing to show that immature and mature stages of the B lineage carry the B-cell receptor of MM cells. These clonal B-cell expansions precede key genetic alterations that are exclusive in MM cells, are detectable at diagnosis and after therapy, and may interfere with serological assessment of treatment efficacy.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006954","title":"Single-cell sequencing of adipose-derived mesenchymal stromal cells and dermal fibroblasts","description":null,"abstract":"Single-cell sequencing of adipose-derived mesenchymal stromal cells and fibroblasts.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-25T10:04:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006955","title":"Understanding_the_transcriptomic_consequences_of_driver_mutations_in_IBD_clonal_expansions_through_laser_capture_microscopy_whole_exome_sequencing","description":"Inflammatory bowel disease (IBD), which is divided into Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic autoinflammatory condition characterized by repeated flares of intestinal inflammation. Three recent studies showed higher mutation rates in IBD affected crypts and that inflammation shapes tissue remodelling leading to positive selection and clonal expansion of crypts harbouring driver mutations. The three studies identified mutations in genes related to IL-17 signaling, cytokine and pattern recognition receptor pathways, rarely affected in colorectal cancer. These studies suggested that clonal expansions are protected from immune-related degradation through pro-apoptosis resistance and that somatic mutagenesis might contribute to the inflammatory process. We aim to expand on this previous work to further validate and define the presented hypotheses by expanding our analysis to RNA by obtaining DNA and RNA from single crypts in IBD patients using laser-capture microdissection (LCM).\n\nWe will collect fresh frozen colonic biopsies and perform exonic and transcriptomic analysis of IBD crypts to investigate the effects of driver muations on the transcriptome. We will use LCM to perform whole-exome and RNA-sequencing of single colonic crypts in IBD patients. Moreover, if exome sequencing appears limited to achieve accurate phylogeny building for some crypts, whole-genome sequencing will be also employed. Later, computational analysis will include phylogeny reconstruction, driver identification and differential gene expression analysis.","abstract":"We will collect fresh frozen colonic biopsies and perform exonic and transcriptomic analysis of IBD crypts to unravel the effects of driver mutations on the transcriptome. We will use LCM whole-exome and RNA-sequencing of single colonic crypts in IBD patients to achieve these goals. If exome sequencing appears limited to achieve accurate phylogeny building for some crypts, whole-genome sequencing will be used instead. Later, computational analysis will include phylogeny reconstruction, driver identification and differential gene expression analysis","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006956","title":"Understanding_the_transcriptomic_consequences_of_driver_mutations_in_IBD_clonal_expansions_through_laser_capture_microscopy_RNA_sequencing","description":"Inflammatory bowel disease (IBD), which is divided into Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic autoinflammatory condition characterized by repeated flares of intestinal inflammation. Three recent studies showed higher mutation rates in IBD affected crypts and that inflammation shapes tissue remodelling leading to positive selection and clonal expansion of crypts harbouring driver mutations. The three studies identified mutations in genes related to IL-17 signaling, cytokine and pattern recognition receptor pathways, rarely affected in colorectal cancer. These studies suggested that clonal expansions are protected from immune-related degradation through pro-apoptosis resistance and that somatic mutagenesis might contribute to the inflammatory process. We aim to expand on this previous work to further validate and define the presented hypotheses by expanding our analysis to RNA by obtaining DNA and RNA from single crypts in IBD patients using laser-capture microdissection (LCM).\n\nWe will collect fresh frozen colonic biopsies and perform exonic and transcriptomic analysis of IBD crypts to investigate the effects of driver muations on the transcriptome. We will use LCM to perform whole-exome and RNA-sequencing of single colonic crypts in IBD patients. Moreover, if exome sequencing appears limited to achieve accurate phylogeny building for some crypts, whole-genome sequencing will be also employed. Later, computational analysis will include phylogeny reconstruction, driver identification and differential gene expression analysis.","abstract":"We will collect fresh frozen colonic biopsies and perform exonic and transcriptomic analysis of IBD crypts to unravel the effects of driver mutations on the transcriptome. We will use LCM whole-exome and RNA-sequencing of single colonic crypts in IBD patients to achieve these goals. If exome sequencing appears limited to achieve accurate phylogeny building for some crypts, whole-genome sequencing will be used instead. Later, computational analysis will include phylogeny reconstruction, driver identification and differential gene expression analysis","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006957","title":"Somatic_Mutations_in_Rheumatoid_Samples_Twist_Exome","description":"The study will explore genetic changes (somatic mutations) that occur throughout life in human joints and in degenerative joint diseases. The data in this study will be generated by whole-exome sequencing of laser-dissected microbiopsies from the synovium of patients with a range of degenerative joint diseases.","abstract":"The study will explore genetic changes (somatic mutations) that occur throughout life in human joints and in degenerative joint diseases. The data in this study will be generated by whole-exome sequencing of laser-dissected microbiopsies from the synovium of patients with a range of degenerative joint diseases.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006958","title":"The multifaceted genomic history of Ashaninka from Amazonian Peru","description":"Genome-wide profiles of Ashaninkas from Peruvian Amazonia reveal two genetic subgroups.\nAshaninka ancestors derived from a south-north migration from southeastern South America.\nThe Ashaninka1 subgroup testifies to an Arawakan-Caribbean genetic link in the Early Ceramic Age.\nThe Ashaninka2 subgroup had recent interactions with Andean and Pacific Indigenous populations.","abstract":"Genome-wide profiles of Ashaninkas from Peruvian Amazonia reveal two genetic subgroups.\nAshaninka ancestors derived from a south-north migration from southeastern South America.\nThe Ashaninka1 subgroup testifies to an Arawakan-Caribbean genetic link in the Early Ceramic Age.\nThe Ashaninka2 subgroup had recent interactions with Andean and Pacific Indigenous populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-26T12:31:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006959","title":"PELICAN45 RNAseq Dataset","description":"To better understand the biology of prostate cancer, we performed RNAseq in cancerous (primary and metastatic) and noncancerous tissues in the PELICAN45 cohort. The PELICAN45 RNAseq samples include androgen-deprived metastasis samples from the PELICAN33 consenting rapid autopsy study participants, whose identifiers are A1, A2, etc.  The PELICAN45 RNAseq dataset also includes data from non-androgen deprived metastases in an additional 12 men. These samples are identified as PB50, PB133, etc.","abstract":"To better understand the biology of prostate cancer, we performed RNAseq in cancerous (primary and metastatic) and noncancerous tissues in the PELICAN45 cohort. The PELICAN45 RNAseq samples include androgen-deprived metastasis samples from the PELICAN33 consenting rapid autopsy study participants, whose identifiers are A1, A2, etc.  The PELICAN45 RNAseq dataset also includes data from non-androgen deprived metastases in an additional 12 men. These samples are identified as PB50, PB133, etc.","study_type":"Other","pubmed_ids":[25830880,27148588,29662167,29728311,32025007,33033260,34337548],"external_links":null,"is_released":true,"released_date":"2023-01-27T10:15:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006960","title":"The effector program of human CD8 T cells can promote both target cell killing and tissue remodeling","description":null,"abstract":"CD8 T lymphocytes are classically viewed as cytotoxic T cells. Whether human CD8 T cells can, in parallel, induce a regenerative program is not understood. Here, antigen-specific assay systems revealed that human CD8 T cells not only mediated cytotoxicity, but also promoted bystander fibroblast and epithelial cell activation, leading to the production of tissue regenerative factors. Tissue remodeling by CD8 T cells could be inhibited by blocking the epidermal growth factor receptor or the effector cytokines IFN- and TNF. The regenerative program also enhanced tumor spheroid and primary organoid growth. Using single-cell chromatin accessibility and gene expression analysis, we identified a tissue-resident CD8 T cell population in healthy donor skin and adipose tissue with a strong TCR clonal relation to blood PD1+TIGIT+ CD8 T cells with tissue remodeling abilities. Our findings may help to understand CD8 in the tumor micromilieu and become relevant for the design of CD8 T-cell therapies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-28T07:52:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006961","title":"IDH mutant Glioma methylation analysis and prognostic signatures","description":null,"abstract":"Genomic profiling of diffuse glioma has advanced our understanding of the disease, where clinically relevant subtypes are defined by presence or absence of somatic mutations in the isocitrate dehydrogenase (IDH) genes and co-deletion of chromosome arms 1p and 19q. However, there remains considerable variability in outcome of each of these glioma subtypes and no known predictors to help direct clinical decision making. We present results of work that focuses on characterizing a methylation signature that can be predictive of outcome in diffuse gliomas. In addition, we performed integrative molecular analysis and identified HOX gene methylation and expression as important factors related to clinically and biologically relevant integrative molecular\nsubtypes in IDH mutant (IDHmut) Lower Grade Glioma (LGG).","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006962","title":"Clonal dynamics of normal hepatocyte expansions in homeostatic human livers and their association with the biliary epithelium","description":"BAM files containing paired-end mtDNA sequencing data from morphologically normal human liver. CCO-proficient hepatocytes acquired from livers in which clonal CCO-deficient hepatocyte patches had been previously identified. Individual BAM files are named according to their patch, line and sample location, where PT denotes tissue near to the portal triad (PT), central hepatic vein (CV) and midway between these two structures (Mid). \"Stroma\" control samples were used for identifying germ-line variants. Sequenced on NextSeq 500 platform.","abstract":"BAM files containing paired-end mtDNA sequencing data from morphologically normal human liver. CCO-proficient hepatocytes acquired from livers in which clonal CCO-deficient hepatocyte patches had been previously identified. Individual BAM files are named according to their patch, line and sample location, where PT denotes tissue near to the portal triad (PT), central hepatic vein (CV) and midway between these two structures (Mid). \"Stroma\" control samples were used for identifying germ-line variants. Sequenced on NextSeq 500 platform.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-01-31T13:22:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006963","title":"GCparagon: Evaluation and correction of GC biases in cell-free DNA at the fragment level","description":"We present GCparagon, a two-stage algorithm for computing and correcting GC biases in cell-free DNA (cfDNA) samples. The length of the highly fragmented cfDNAs and the number of GC bases are essential parameters in the calculations. Regions of low mappability, known reference genome assembly errors and regions surrounding assembly gaps are excluded from the bias computation. GCparagon outputs a bias matrix and an optional tagged BAM file with GC bias balance weights as alignment tags. Parallelization allows calculation of a GC bias estimate in less than 2 minutes per sample with between 99.0% and 99.9% of fragments already corrected. We propose that GCparagon can help standardize cfDNA applications and evaluate the impact of GC bias on algorithms used in the analysis of liquid biopsy data.","abstract":"We present GCparagon, a two-stage algorithm for computing and correcting GC biases in cell-free DNA (cfDNA) samples. The length of the highly fragmented cfDNAs and the number of GC bases are essential parameters in the calculations. Regions of low mappability, known reference genome assembly errors and regions surrounding assembly gaps are excluded from the bias computation. GCparagon outputs a bias matrix and an optional tagged BAM file with GC bias balance weights as alignment tags. Parallelization allows calculation of a GC bias estimate in less than 2 minutes per sample with between 99.0% and 99.9% of fragments already corrected. We propose that GCparagon can help standardize cfDNA applications and evaluate the impact of GC bias on algorithms used in the analysis of liquid biopsy data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-01T13:09:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006964","title":"A novel Patient-Derived 3D Model Recapitulates Mantle Cell Lymphoma Lymph Node Signaling, Immune Profile and in vivo Ibrutinib Responses","description":"RNA-seq data from CD20+ sorted cells obtained from peripheral blood Mantle Cell Lymphoma patients. These samples were unstimulated after thawing or stimulated during 7 days in culture as described in Araujo-Ayala F et. al.","abstract":"RNA-seq data from CD20+ sorted cells obtained from peripheral blood Mantle Cell Lymphoma patients. These samples were unstimulated after thawing or stimulated during 7 days in culture as described in Araujo-Ayala F et. al.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-01T16:52:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006965","title":"Chronic lymphocytic leukemia patient-derived xenografts recapitulate clonal evolution to Richter transformation","description":"Whole-genome sequencing (WGS) and RNA-seq data from patient-derived xenografts (PDXs) obtained from CLL and RT primary samples as described in Playa-Albinyana et al.","abstract":"Whole-genome sequencing (WGS) and RNA-seq data from patient-derived xenografts (PDXs) obtained from CLL and RT primary samples as described in Playa-Albinyana et al.","study_type":"Other","pubmed_ids":[38017105],"external_links":null,"is_released":true,"released_date":"2023-02-01T17:44:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006966","title":"RNA-seq on bronchial brushings collected in controlled human exposure to diesel exhaust","description":"COPA study examined the impact of short-term exposure on airway epithelium transcriptome. It was a randomized, double-blind, controlled human exposure study to diesel exhaust with a crossover design. This human study was registered on clinicaltrials.gov with the identifier NCT02236039.","abstract":"COPA study examined the impact of short-term exposure on airway epithelium transcriptome. It was a randomized, double-blind, controlled human exposure study to diesel exhaust with a crossover design. This human study was registered on clinicaltrials.gov with the identifier NCT02236039.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-01T18:29:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006967","title":"Personalized Onco-Genomic Project for pediatric and adolescent patients in British Columbia","description":"This is an extension of the BC Cancer Agency's Personalized Onco-Genomics (POG) project to children and adolescents treated at BC Children's Hospital. The project provides access to whole genome and transcriptome sequencing, and integrated bioinformatics analyses, of relapsed, refractory or poor prognosis cancers with an aim to identify actionable variants that can inform clinical decision making.","abstract":"This is an extension of the BC Cancer Agency's Personalized Onco-Genomics (POG) project to children and adolescents treated at BC Children's Hospital. The project provides access to whole genome and transcriptome sequencing, and integrated bioinformatics analyses, of relapsed, refractory or poor prognosis cancers with an aim to identify actionable variants that can inform clinical decision making.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-01T22:25:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006968","title":"Longitudinal peripheral blood DNA methylation profiling of endoscopic response to tofacitinib in moderate-to-severe ulcerative colitis patients","description":null,"abstract":"Despite proven clinical efficacy of tofacitinib in ulcerative colitis (UC), merely 31.3% of patients achieve mucosal healing at week 8. Therefore, predictive biomarkers that allow for pre-treatment selection are urgently needed. Here, we performed a longitudinal case-control study investigating whether the DNA methylome of peripheral blood (PB) was capable of prognostically predicting response to tofacitinib. We prospectively recruited moderate-to-severe adult UC patients, scheduled to start tofacitinib treatment and measured their PB DNA methylation profiles prior to treatment during baseline endoscopy (T1; N = 31), after 8 weeks (T2; N = 17) and for a subset after a median of 20 weeks (T3; N = 8) into treatment using the Illumina Infinium HumanMethylation EPIC BeadChip. After 8 weeks of treatment, patients were categorized as responders (R) or non-responders (NR) based on a centrally read endoscopic evaluation in combination with steroid-free clinical response and/or biochemical response. Samples taken at T1 were used for biomarker identification and classification analyses using stability selected gradient boosting.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-02T07:43:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006969","title":"HCA_Female_Reproductive_Endometriosis_Magda_Funds_Spatial_Managed_Access","description":"HCA Female Reproductive Endometriosis_spatial","abstract":"A collaborative multi-institute project, using single cell atlasing and spatial techniques on endometrium samples and endometriosis cases to investigate endometriosis disease mechanisms, and endometrial cell biology.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006970","title":"Single-cell RNA-seq and spatial transcriptomics data for the sarcoidosis baseline project","description":"Granulomas are lumps of immune cells that can form in various organs. Most granulomas appear unstructured, yet they have some resemblance to lymphoid organ formation. To better understand granuloma formation, we performed single-cell sequencing and spatial transcriptomics on granulomas from patients with sarcoidosis and bioinformatically reconstructed the underlying gene-regulatory networks. We discovered an immune stimulatory environment in granulomas that repurposed transcriptional programs associated with lymphoid organ development. Granuloma formation followed characteristic spatial patterns and involved genes linked to immunometabolism, cytokine and chemokine signaling, and extracellular matrix remodeling. Three cell types emerged as key players in granuloma formation: metabolically reprogrammed macrophages, cytokine-producing Th17.1 cells, and fibroblasts with inflammatory and tissue remodeling phenotypes. Pharmacological inhibition of one of the identified processes attenuated granuloma formation in a sarcoidosis mouse model. We show that human granulomas adopt characteristic aspects of normal lymphoid organ development in aberrant combinations, indicating that granulomas constitute aberrant lymphoid organs.","abstract":"Granulomas are lumps of immune cells that can form in various organs. Most granulomas appear unstructured, yet they have some resemblance to lymphoid organ formation. To better understand granuloma formation, we performed single-cell sequencing and spatial transcriptomics on granulomas from patients with sarcoidosis and bioinformatically reconstructed the underlying gene-regulatory networks. We discovered an immune stimulatory environment in granulomas that repurposed transcriptional programs associated with lymphoid organ development. Granuloma formation followed characteristic spatial patterns and involved genes linked to immunometabolism, cytokine and chemokine signaling, and extracellular matrix remodeling. Three cell types emerged as key players in granuloma formation: metabolically reprogrammed macrophages, cytokine-producing Th17.1 cells, and fibroblasts with inflammatory and tissue remodeling phenotypes. Pharmacological inhibition of one of the identified processes attenuated granuloma formation in a sarcoidosis mouse model. We show that human granulomas adopt characteristic aspects of normal lymphoid organ development in aberrant combinations, indicating that granulomas constitute aberrant lymphoid organs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-02T09:38:12+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006971","title":"HCA_Female_Reproductive_Endometriosis_Magda_Funds_RNA_Managed_Access","description":"HCA Female Reproductive Endometriosis_RNA","abstract":"A collaborative multi-institute project, using single cell atlasing and spatial techniques on endometrium samples and endometriosis cases to investigate endometriosis disease mechanisms, and endometrial cell biology.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006972","title":"HCA_Female_Reproductive_Endometriosis_Magda_Funds_DNA_Managed_Access","description":"HCA Female Reproductive Endometriosis_DNA","abstract":"A collaborative multi-institute project, using single cell atlasing and spatial techniques on endometrium samples and endometriosis cases to investigate endometriosis disease mechanisms, and endometrial cell biology.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006973","title":"Treated and control Patient Derived Xenografts of colorectal cancer (CRC) samples","description":null,"abstract":"Bank of treateed and control PDXs metastastic colorectal cancer sample RNAseq","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-02T13:50:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006974","title":"Effect_of_ADCY7_risk_variant_on_immune_cells","description":"we hypothesize that genetic variants affecting genes involved in cAMP metabolism could lead to an abnormal inflammatory response, contributing to the increased risk of developing IBD. Our group has reported a missense variant in an enzyme called adenylate cyclase 7(ADCY7). This missense variant (p.Asp439Glu, rs78534766) doubles the risk of ulcerative colitis (OR=2.19) and is predicted to alter protein function (PolyPhen=1). In addition to ADCY7, other IBD risk variants have been described in intronic regions of ADCY3 (ADCY7 isoenzyme).\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We aim to define the role of rs78534766 (ADCY7 missense variant, A) and ADCY3 risk locus (tagged by rs11676272, G) in gene expression in immune cells. Our preliminary data show that indels induced by CRISPR/Cas9 on ADCY7 gene in T cells lead to an increase in TNF-α production, suggesting a possible role of this gene in cytokine regulation and/or cell activation. Here, we propose to analyse the transcriptional consequences of carrying ADCY7 risk variant (rs78534766, A) or ADCY3 risk locus (12 genetic variants in high LD R2 &gt;0.95 and tagged by rs11676272, G- eQTL for ADCY3 in T cells ) in blood cells.\nWe will sort neutrophils, T cells and monocytes from peripheral blood of risk variant carriers or non-carriers followed by bulk RNA-sequencing. These experiments will inform us on: a) the blood cell type(s) in which these risk variants are active and b) which biological pathways these genetic variants modulate. In parallel, we will use blood samples from the same individuals to compare secretion of TNF-α (as suggested by CRISPR experiments) and production of cAMP (measurement of ADCY7 and ADCY3 activity). We have recently been granted the approval from the NIHR BioResource for Translational Research to recruit five volunteers for each genotype (due to low frequency of risk allele in rs78534766, heterozygous will be recalled) for a pilot experiment.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006975","title":"A capture-based next-generation sequencing panel for the molecular characterization of chronic lymphocytic leukemia","description":null,"abstract":"Capture-based next-generation sequencing (NGS) data generated using a custom chronic lymphocytic leukemia (CLL) gene panel designed to capture driver gene mutations, copy number alterations and immunoglobulin gene rearrangements. Samples from two different cohorts (retrospective, 25 patients; prospective, 87 patients).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-02T13:54:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006976","title":"B Cell Receptor Study From Metastatic Breast Cancer Tumour Samples","description":"B and T cells are key components of the adaptive immune system and play an important role in anti-cancer immunity. In this study, we performed an integrative analysis of the B cell and T cell repertoires across 27 metastatic breast tumours obtained from 8 donors with therapy-resistant lethal metastatic breast cancer at the time of a warm autopsy.","abstract":"B and T cells are key components of the adaptive immune system and play an important role in anti-cancer immunity. In this study, we performed an integrative analysis of the B cell and T cell repertoires across 27 metastatic breast tumours obtained from 8 donors with therapy-resistant lethal metastatic breast cancer at the time of a warm autopsy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-02T15:39:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006977","title":"NanoString nCounter® PanCancer IO 360™on anti-PD1/anti-PD1+CTLA4 in patients with metastatic melanoma","description":"Patients with advanced melanoma were treated with standard-of-care single agent anti-PD-1 (nivolumab or pembrolizumab) or a combined anti-PD-1+anti-CTLA-4 (ipilimumab) therapy. Patients were retrospectively identified, based on formalin-fixed paraffin-embedded (FFPE) tissue availability. \nTotal RNA was isolated from macro-dissected FFPE tissue sections using the AllPrep DNA/RNA FFPE Kit (Qiagen) or High Pure FFPET RNA Isolation Kit (Roche) according to the manufacturer’s instructions. RNA quantity was assessed on Qubit, and RNA integrity was assessed using the Tapestation system (Agilent). Total RNA samples (60ng/ul, total 200ng) were used as input for the NanoString PanCancer IO360 Panel, run on the nCounter MAX/FLEX prep station and scanner. Samples were hybridised for 20hrs, and each cartridge contained a panel standard.","abstract":"Patients with advanced melanoma were treated with standard-of-care single agent anti-PD-1 (nivolumab or pembrolizumab) or a combined anti-PD-1+anti-CTLA-4 (ipilimumab) therapy. Patients were retrospectively identified, based on formalin-fixed paraffin-embedded (FFPE) tissue availability. \nTotal RNA was isolated from macro-dissected FFPE tissue sections using the AllPrep DNA/RNA FFPE Kit (Qiagen) or High Pure FFPET RNA Isolation Kit (Roche) according to the manufacturer’s instructions. RNA quantity was assessed on Qubit, and RNA integrity was assessed using the Tapestation system (Agilent). Total RNA samples (60ng/ul, total 200ng) were used as input for the NanoString PanCancer IO360 Panel, run on the nCounter MAX/FLEX prep station and scanner. Samples were hybridised for 20hrs, and each cartridge contained a panel standard.","study_type":"Other","pubmed_ids":[37055772],"external_links":null,"is_released":true,"released_date":"2023-02-03T01:24:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006978","title":"Exome_sequencing_of_UK_Birth_Cohorts___Born_in_Bradford","description":"We propose to exome sequence birth cohorts with near complete population coverage (thus addressing the ascertainment biases of previous studies), which have detailed longitudinal cognitive and educational data on parents and children, and for which genotyping chip data are readily available.","abstract":"Birth cohort studies involve repeated surveys of large numbers of individuals from birth and throughout their lives. They collect information useful for a wide range of life course research domains, and biological samples which can be used to derive data from an increasing collection of omic technologies. This rich source of longitudinal data, when combined with genomic data, offers the scientific community valuable insights from population genetics to rare disease associations.\n\nAvon Longitudinal Study of Parents and Children (ALSPAC)recruited 14,775 babies of predominantly White ethnicity in the Avon county of south-west England between 1991 and 1992. Born in Bradford (BiB) is similarly focused on a particular local area, the city of Bradford in the north of England, and recruited 13,858 babies between 2007 and 2011, of whom ~41% self-report as white British and ~59% as other ethnicities, predominantly Pakistani. Millennium Cohort Study (MCS) is a national cohort that recruited 18,827 children born between 2000 and 2002, intentionally over-sampling areas with high child poverty, large ethnic minority populations, and smaller UK nations (Wales, Scotland and Northern Ireland)\n\n \n\nAvailable here is a subset of exome-sequenced parents and children from these studies (CRAMS and post-QC VCFs) as detailed in this data note.\n\n \n\nPhenotypic data is also available  by submitting an application to the corresponding cohort:\n\nhttps://borninbradford.nhs.uk/ [borninbradford.nhs.uk]","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-06T14:56:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006979","title":"Novel Immunodeficiency caused by homozygous mutation of SLC19A1 discovered by exome sequencing of one affected proband.","description":null,"abstract":"The male proband suffered from infancy oral lesions, recurrent fever, diarrhea, vomiting, atopic dermatitis, dark discoloration patches on his skin and lip fissures; he suffered from anemia (megaloblastic), thrombocytopenia, hypogammaglobulinemia and lymphopenia; his growth and development are delayed. Whole exome sequencing identified only one variant predicted to have high impact and to potentially explain the patient’s phenotype, a homozygous missense chr21:46950793:C:T (hg19) SLC19A1 NM_194255:c.1042G&gt;A (p.G348R). Sanger sequencing and segregation analysis confirmed the presence of the homozygous SLC19A1 c.1042G&gt;A (G348R) missense variant in the proband, with a heterozygous state in his family. The same homozygous SLC19A1 variant was identified in a distantly-related male patient with a similar phenotype presentation, while his healthy family members were heterozygous. SLC19A1 is a folate transporter, and thus folic acid supplementation was performed for the proband: platelet counts normalized rapidly and anemia improved; hair and skin discoloration, mouth lesions and chronic diarrhea improved. In contrast, neurological and developmental issues remained unchanged and treatment had only a partial effect on the immune system. This further confirmed the causal role of SLC19A1 for the proband's condition.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006980","title":"scRNA-seq of total bone marrow mononuclear cells and CD3+ T cells of multiple myeloma patients and healthy donors","description":"The study includes 50 scRNA-seq samples of bone marrow aspirates of 11 multiple myeloma patients and 3 healthy donors generated with the 10x Genomics platform (Chromium Single Cell 3’ Solution v2). For the multiple myeloma patients, paired longitudinal samples are available from initial diagnosis and long-term surivor state. For each patient and timepoint, total bone marrow mononuclear cells and CD3+ T cells have been sequenced separately.","abstract":"The study includes 50 scRNA-seq samples of bone marrow aspirates of 11 multiple myeloma patients and 3 healthy donors generated with the 10x Genomics platform (Chromium Single Cell 3’ Solution v2). For the multiple myeloma patients, paired longitudinal samples are available from initial diagnosis and long-term surivor state. For each patient and timepoint, total bone marrow mononuclear cells and CD3+ T cells have been sequenced separately.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-06T16:03:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006981","title":"HLA-DR is absent in primitive macrophages through epigenetic silencing of master regulator CIITA","description":"The earliest macrophages are generated during embryonic development from erythro-myeloid progenitors (EMPs) via primitive haematopoiesis. This process is poorly understood in humans and in the mouse is thought to be spatially restricted to the yolk sac. Human fetal placental macrophages, Hofbauer cells (HBC), arise during the primitive haematopoietic wave at ~18 days post conception. Here we identify a population of placental erythro-myeloid progenitors (PEMPs) in the early human placenta that give rise to HBC. PEMP are fetal CD34+CD43+ progenitors found exclusively at early gestational timepoints. Transcriptomic analyses reveal that PEMP have conserved features of primitive yolk sac EMPs, including the lack of HLF expression. Using in vitro single-cell culture experiments we show that PEMP generate HBC-like cells that completely lack HLA-DR expression  and demonstrate that this is a conserved feature of all macrophages generated by primitive haematopoiesis in humans. Finally, we demonstrate that the class II transactivator, CTIIA, the master regulator HLA-DR expression, is epigenetically silenced during primitive haematopoiesis, leading to HLA-DRneg macrophages. These findings demonstrate that HBC are derived locally from PEMP and establish the human placenta as an additional site of primitive haematopoiesis.","abstract":"The earliest macrophages are generated during embryonic development from erythro-myeloid progenitors (EMPs) via primitive haematopoiesis. This process is poorly understood in humans and in the mouse is thought to be spatially restricted to the yolk sac. Human fetal placental macrophages, Hofbauer cells (HBC), arise during the primitive haematopoietic wave at ~18 days post conception. Here we identify a population of placental erythro-myeloid progenitors (PEMPs) in the early human placenta that give rise to HBC. PEMP are fetal CD34+CD43+ progenitors found exclusively at early gestational timepoints. Transcriptomic analyses reveal that PEMP have conserved features of primitive yolk sac EMPs, including the lack of HLF expression. Using in vitro single-cell culture experiments we show that PEMP generate HBC-like cells that completely lack HLA-DR expression  and demonstrate that this is a conserved feature of all macrophages generated by primitive haematopoiesis in humans. Finally, we demonstrate that the class II transactivator, CTIIA, the master regulator HLA-DR expression, is epigenetically silenced during primitive haematopoiesis, leading to HLA-DRneg macrophages. These findings demonstrate that HBC are derived locally from PEMP and establish the human placenta as an additional site of primitive haematopoiesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-06T18:04:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006982","title":"Diet driven microbial ecology underpins associations between cancer immunotherapy outcomes and the gut microbiome","description":"This study profiled baseline gut (fecal) microbiota signatures and dietary patterns of 103 trial patients from Australia and the Netherlands treated with neoadjuvant ICIs for high risk resectable metastatic melanoma and performed an integrated analysis with data from 115 patients with melanoma treated with ICIs in the United States. We observed geographically distinct microbial signatures of response and immune-related adverse events. Overall, response rates were higher in Ruminococcaceae-dominated microbiomes than in Bacteroidaceae-dominated microbiomes. Poor response was associated with lower fiber and omega 3 fatty acid consumption and elevated levels of C-reactive protein in the peripheral circulation at baseline.","abstract":"This study profiled baseline gut (fecal) microbiota signatures and dietary patterns of 103 trial patients from Australia and the Netherlands treated with neoadjuvant ICIs for high risk resectable metastatic melanoma and performed an integrated analysis with data from 115 patients with melanoma treated with ICIs in the United States. We observed geographically distinct microbial signatures of response and immune-related adverse events. Overall, response rates were higher in Ruminococcaceae-dominated microbiomes than in Bacteroidaceae-dominated microbiomes. Poor response was associated with lower fiber and omega 3 fatty acid consumption and elevated levels of C-reactive protein in the peripheral circulation at baseline.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-06T18:25:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006983","title":"Study of complex rearrangements and mutational signatures in neuroblastoma heterogeneous risk groups.","description":"Neuroblastoma is a pediatric solid tumor characterized by strong clinical heterogeneity. Although certain complex genomic alterations, such as extrachromosomal DNA amplifications (ecDNA), are associated with adverse outcome and have been recurrently detected in neuroblastomas, the mutational processes involved in their generation remain largely unclear. By examining the topography of complex rearrangements along with mutational signatures derived from all variant classes, we identify previously unrecognized co-occurring mutational footprints, which we termed mutational scenarios. We demonstrate that clinical neuroblastoma heterogeneity is linked to differences in the processes driving these mutational scenarios. Whereas high-risk MYCN-amplified neuroblastoma genomes were characterized by signs of replication slippage and stress, homologous recombination-associated signatures defined high-risk non-MYCN-amplified patients. Non-high-risk neuroblastomas, on the other hand, were marked by footprints of chromosome missegregation and TOP1 mutational activity. This analysis provides a systematic perspective on the repertoire of mutational patterns that contribute to clinical neuroblastoma heterogeneity.","abstract":"Neuroblastoma is a pediatric solid tumor characterized by strong clinical heterogeneity. Although certain complex genomic alterations, such as extrachromosomal DNA amplifications (ecDNA), are associated with adverse outcome and have been recurrently detected in neuroblastomas, the mutational processes involved in their generation remain largely unclear. By examining the topography of complex rearrangements along with mutational signatures derived from all variant classes, we identify previously unrecognized co-occurring mutational footprints, which we termed mutational scenarios. We demonstrate that clinical neuroblastoma heterogeneity is linked to differences in the processes driving these mutational scenarios. Whereas high-risk MYCN-amplified neuroblastoma genomes were characterized by signs of replication slippage and stress, homologous recombination-associated signatures defined high-risk non-MYCN-amplified patients. Non-high-risk neuroblastomas, on the other hand, were marked by footprints of chromosome missegregation and TOP1 mutational activity. This analysis provides a systematic perspective on the repertoire of mutational patterns that contribute to clinical neuroblastoma heterogeneity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-07T08:43:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006984","title":"RNA sequencing of CCO- and CCO+ human hepatocytes","description":"RNAseq data from Passman et al 2023. Clonal CCO-deficient hepatocyte patches and nearby CCO-proficient hepatocytes were identified in morphologically normal human livers and sampled at varying distances along the PT-CV axis. Samples are named according to their location within the liver lobule, with \"PT\" denoting samples abutting the portal triad, \"CV\" denoting samples abutting the central hepatic vein, and \"Mid\" sampled acquired midway between these structures.\n\nNormal human liver is thought to be generally quiescent, however clonal hepatocyte expansions have been observed but neither their cellular source nor their expansion dynamics have been determined. Knowing the hepatocyte cell of origin, and their subsequent dynamics and trajectory within the human liver will provide an important basis to understand disease-associated dysregulation.\n\nHere we use in vivo lineage tracing and a combination of methylation sequence analysis to demonstrate normal human hepatocyte ancestry. We exploit next generation mitochondrial sequencing to determine hepatocyte clonal expansion dynamics across spatially-distinct areas of laser-capture microdissected clones, in tandem with computational modelling in morphologically-normal human liver.","abstract":"RNAseq data from Passman et al 2023. Clonal CCO-deficient hepatocyte patches and nearby CCO-proficient hepatocytes were identified in morphologically normal human livers and sampled at varying distances along the PT-CV axis. Samples are named according to their location within the liver lobule, with \"PT\" denoting samples abutting the portal triad, \"CV\" denoting samples abutting the central hepatic vein, and \"Mid\" sampled acquired midway between these structures.\n\nNormal human liver is thought to be generally quiescent, however clonal hepatocyte expansions have been observed but neither their cellular source nor their expansion dynamics have been determined. Knowing the hepatocyte cell of origin, and their subsequent dynamics and trajectory within the human liver will provide an important basis to understand disease-associated dysregulation.\n\nHere we use in vivo lineage tracing and a combination of methylation sequence analysis to demonstrate normal human hepatocyte ancestry. We exploit next generation mitochondrial sequencing to determine hepatocyte clonal expansion dynamics across spatially-distinct areas of laser-capture microdissected clones, in tandem with computational modelling in morphologically-normal human liver.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-07T12:38:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006985","title":"Teratoma_WGS","description":"DNA and RNA sequencing across a number of different germ cell tumours, included mixed components within the same tumour.","abstract":"This study aims to characterise the genetic and transcriptomic profile of germ cell tumours, in particular to develop a phylogenetic tree within mixed germ cell tumours to provide insight into their development and cell of origin, both of which are currently poorly understood.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006986","title":"Reprogramming of stroma-derived chemokine networks drives the loss of tissue organization in nodal B cell lymphoma","description":"Here, we utilized single-cell and spatial mapping to interrogate the mechanisms directing tissue architecture in human lymph nodes (LN) and its disruption in nodal B cell lymphoma. Specifically, we mapped the cellular landscape of follicular lymphoma (FL; n=6) and diffuse large B cell lymphoma (DLBCL; n=8) alongside non-malignant reactive LNs (rLN; n=5) using single-cell RNA sequencing. Our data support the central role of LN-resident stromal cells in chemokine-driven lymphocyte zonation and reveal an inflammatory feedback loop fueled by tumor-reactive T cells, triggering stromal remodeling, progressive loss of homeostatic chemokine gradients and tissue organization from non-malignant to FL and DLBCL. Collectively, our results highlight the principles of LN organization and suggest how lymphoma-induced microenvironmental reprogramming drives loss of tissue organization.","abstract":"Here, we utilized single-cell and spatial mapping to interrogate the mechanisms directing tissue architecture in human lymph nodes (LN) and its disruption in nodal B cell lymphoma. Specifically, we mapped the cellular landscape of follicular lymphoma (FL; n=6) and diffuse large B cell lymphoma (DLBCL; n=8) alongside non-malignant reactive LNs (rLN; n=5) using single-cell RNA sequencing. Our data support the central role of LN-resident stromal cells in chemokine-driven lymphocyte zonation and reveal an inflammatory feedback loop fueled by tumor-reactive T cells, triggering stromal remodeling, progressive loss of homeostatic chemokine gradients and tissue organization from non-malignant to FL and DLBCL. Collectively, our results highlight the principles of LN organization and suggest how lymphoma-induced microenvironmental reprogramming drives loss of tissue organization.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-07T15:31:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006987","title":"SMARCA4-associated schwannomatosis","description":null,"abstract":"Our study showcases a family that has a germline likely pathogenic SMARCA4 variant and presented with multiple schwannomas. Immunohistochemical, whole exome sequencing and methylation analyses on the proband and her affected mother's samples suggest that SMARCA4 was the cause of the schwannomas, rather than the Chromosome 22q schwannomatosis genes. Our results lead us to propose SMARCA4 as a candidate schwannomatosis gene.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006988","title":"Multiomic Sequencing of Paired Primary and Metastatic Small Bowel Carcinoids","description":"Small bowel carcinoids are insidious tumors that often have metastatic spread at the time of diagnosis. Limited studies on the mutational landscape of carcinoids indicate that the tumors have a relatively low mutational burden. Loss of chromosome 18q and loss of CDKN1B have been reported in a minority of tumors. The development of targeted therapies will depend upon the identification of mutations that drive the pathogenesis and metastasis of carcinoid tumors.","abstract":"Small bowel carcinoids are insidious tumors that often have metastatic spread at the time of diagnosis. Limited studies on the mutational landscape of carcinoids indicate that the tumors have a relatively low mutational burden. Loss of chromosome 18q and loss of CDKN1B have been reported in a minority of tumors. The development of targeted therapies will depend upon the identification of mutations that drive the pathogenesis and metastasis of carcinoid tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-08T00:47:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006989","title":"Pharmacogenomic profiling reveals molecular features of chemotherapy resistance in IDH wild type primary glioblastoma","description":"We stratified 69 primary IDH-wt GBM patients into TMZ-resistant (n = 29) and sensitive (n = 40) groups, using TMZ screening of the corresponding patient-derived glioma stem-like cells (GSCs). Genomic and transcriptomic features were then examined to identify TMZ-associated molecular alterations. Subsequently, we developed a machine learning (ML) model to predict TMZ response from combined signatures. Moreover, TMZ response in multisector samples (52 tumor sectors from 18 cases) was evaluated to validate findings and investigate the impact of intra-tumoral heterogeneity on TMZ efficacy.","abstract":"We stratified 69 primary IDH-wt GBM patients into TMZ-resistant (n = 29) and sensitive (n = 40) groups, using TMZ screening of the corresponding patient-derived glioma stem-like cells (GSCs). Genomic and transcriptomic features were then examined to identify TMZ-associated molecular alterations. Subsequently, we developed a machine learning (ML) model to predict TMZ response from combined signatures. Moreover, TMZ response in multisector samples (52 tumor sectors from 18 cases) was evaluated to validate findings and investigate the impact of intra-tumoral heterogeneity on TMZ efficacy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-08T03:57:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006990","title":"A single cell view on host immune transcriptional response to in vivo BCG-induced trained immunity","description":null,"abstract":"Bacillus Calmette-Guerin (BCG) vaccination is a prototype model for the study of trained immunity (TI) in humans, and results in a more effective response of innate immune cells upon stimulation with heterologous stimuli. Here we investigated the heterogeneity of TI induction by single-cell RNA-seq of immune cells collected from 156 samples. We observed that both monocytes and CD8+ T cells showed heterologous transcriptional responses to lipopolysaccharide, with an active crosstalk between these two cell types. Furthermore, the interferon-gamma pathway was crucial in BCG-induced TI, and it was up-regulated in functional high-responders. Data-driven analyses and functional experiments revealed STAT1 to be one of the important transcription factors for TI shared in all newly identified monocyte sub-populations. Finally, we reported the role of type I interferon-related and neutrophil-related TI transcriptional programs in patients with sepsis. These findings provided comprehensive insights into the importance of monocyte heterogeneity during TI in humans.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-08T08:50:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006991","title":"Christina","description":"Christina","abstract":"Christina","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006992","title":"Molecular analysis of cancer genomes in children with Lynch syndrome: exploring causal associations","description":"Molecular characterization of 20 tumors of 18 children with Lynch syndrome to investigate causality. This characterization includes the investigation of second hits, tumor mutational load, mutational signatures and MMR protein expression.","abstract":"Molecular characterization of 20 tumors of 18 children with Lynch syndrome to investigate causality. This characterization includes the investigation of second hits, tumor mutational load, mutational signatures and MMR protein expression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-09T15:44:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006993","title":"Genomic landscape of ETMR","description":null,"abstract":"ETMRs are increasingly recognized as one of the most common, lethal infant embryonal brain tumors, driven by an oncogenic C19MC amplification. However, little is known about the ETMR genome and how it contributes to histologic and clinical heterogeneity. Herein, we performed systematic whole genome and RNA-sequencing and single cell RNA-sequencing analysis to further interrogate the ETMR genome and transcriptome.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006994","title":"Single cell multi-omic study of H3-K27M mutant diffuse midline glioma across age and location","description":"Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in childhood diffuse midline gliomas (DMGs) of the pons, but are also increasingly recognized in adult DMGs. Their potential heterogeneity at different ages and midline locations are vastly understudied. Here, through dissecting the single-cell transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We conducted multi-omic profiling of 50 H3-K27M mutant patient tumors. We performed deep full-length Smart-seq2 fresh single-cell (n=18) or frozen single-nucleus (n=25) RNA-sequencing (sc/snRNA-seq) of 43 tumors). We additionally analyzed the open chromatin profiles of 8 tumors utilizing the single-cell/nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq)","abstract":"Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in childhood diffuse midline gliomas (DMGs) of the pons, but are also increasingly recognized in adult DMGs. Their potential heterogeneity at different ages and midline locations are vastly understudied. Here, through dissecting the single-cell transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We conducted multi-omic profiling of 50 H3-K27M mutant patient tumors. We performed deep full-length Smart-seq2 fresh single-cell (n=18) or frozen single-nucleus (n=25) RNA-sequencing (sc/snRNA-seq) of 43 tumors). We additionally analyzed the open chromatin profiles of 8 tumors utilizing the single-cell/nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-09T20:25:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006995","title":"Germline variants in childhood cutaneous melanoma","description":null,"abstract":"Germline variants in individuals with cutaneous melanoma diagnosed prior to 18 years of age.","study_type":"Exome Sequencing","pubmed_ids":[36863448],"external_links":null,"is_released":true,"released_date":"2023-02-10T04:02:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001006996","title":"X chromosome dosage and the genetic impact across human tissues","description":null,"abstract":"Sex chromosome aneuploidies (SCAs) gives rise to a broad range of phenotypic traits and diseases. Previous studies based on peripheral blood samples have suggested the presence of ripple effects, caused by altered X chromosome dosage, affecting the methylome and transcriptome. If these alterations can be connected to disease specific tissues, and thereby having clinical implication for the phenotype, remains to be elucidated. We performed a comprehensive analysis of X chromosome dosage on the methylome and transcriptome in blood, fat and muscle tissue from individuals with 45,X, 46,XX, 46,XY and 47,XXY. X chromosome dosage affected the methylome and transcriptome globally across all chromosomes in a highly tissue specific manner. Furthermore, 45,X and 47,XXY demonstrated a divergent pattern of methylation and gene expression, with predominantly hypomethylation and gene downregulation in 45,X and hypermethylation and gene upregulation in 47,XXY. In fat and muscle, a pronounced effect of sex was observed. Moreover, we identified X chromosomal genes deviating from the classic X chromosome dosage compensation theory and a regulatory function of Y chromosomal genes on X chromosomal genes. Fourteen X chromosomal genes were downregulated in 45,X and upregulated in 47,XXY, respectively, in all three tissues (AKAP17A, CD99, DHRSX, EIF2S3, GTPBP6, JPX, KDM6A, PP2R3B, PUDP, SLC25A6, TSIX, XIST, ZBED1, ZFX). These genes may be central in the epigenetic and genomic regulation of sex chromosome aneuploidies. In conclusion, we highlight a complex effect of X dosage on the methylome and transcriptome, elucidating both shared and non-shared gene regulatory mechanism between SCAs as well as tissue-specific regulation.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006997","title":"DERMATLAS__Syringocystadenoma_papilliferum_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are syringocystadenoma papilliferum (SCAP).","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are syringocystadenoma papilliferum (SCAP).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006998","title":"Targeted_NanoSeq_from_non_invasive_breast_milk_samples","description":"Targeted NanoSeq in non-invasive samples from individuals with genetic predisposition (BRCA1, BRCA2) or generally high-risk for breast cancer. In addition, samples from womean at intermediate risk will be sequenced. A custom-designed panel of ~200 genes, SNPs and copy number regions will be used to achieve high depth coverage (aiming for ~1000X at panel sites). The driver landscape different risk groups as well as between breast tissue and breast milk will be compared. Overall, we aim to assess the predictive value of somatic mutations for cancer risk prediction.","abstract":"Targeted NanoSeq in non-invasive samples from individuals with genetic predisposition (BRCA1, BRCA2) or generally high-risk for breast cancer. In addition, samples from womean at intermediate risk will be sequenced. A custom-designed panel of ~200 genes, SNPs and copy number regions will be used to achieve high depth coverage (aiming for ~1000X at panel sites). The driver landscape different risk groups as well as between breast tissue and breast milk will be compared. Overall, we aim to assess the predictive value of somatic mutations for cancer risk prediction.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001006999","title":"PhIP-Seq LLD","description":"Bacteriophage Immunoprecipitation Sequencing (PhIP-Seq) of LLD participants. Libraries and protocol were developed in the Weizmann Institute of Science. Two different libraries were used, containing microbial and other immunological peptides respectively.","abstract":"Bacteriophage Immunoprecipitation Sequencing (PhIP-Seq) of LLD participants. Libraries and protocol were developed in the Weizmann Institute of Science. Two different libraries were used, containing microbial and other immunological peptides respectively.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-13T10:03:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007000","title":"Humoral and cellular immune perturbations in immune checkpoint inhibitor-related myositis and myocarditis","description":null,"abstract":"Understanding the predictors and mechanisms of severe, organ-specific autoimmune toxicities of immune checkpoint inhibitors (ICI) is critical to optimal use of these promising agents. Immune-mediated myositis and myocarditis are potentially life-threatening toxicities of ICI. Because these immune-related adverse events (irAE) are exceedingly rare, little is known about their underlying biologic features. By accessing a cohort of almost 400 patients treated with ICI, we were able to study the humoral and cellular features of six patients with myositis/myocarditis irAE. As has been noted with other irAE, features of these toxicities differed somewhat from non-ICI-related comparable conditions. For instance, we did not observe clear autoantibody profiles distinguishing these cases from control patients with no toxicity. However, we did identify a distinct pattern of immune dysregulation in myositis/myocarditis cases, apparent in cytokine, cellular, and gene expression profiles. Among these cases, a single fatal myocarditis irAE featured unique baseline and post-treatment immune parameters. This information could aid in development of individualized monitoring and early detection measures.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007001","title":"Biomarker Screen for Efficacy of Oncolytic Virotherapy in Patient-derived Pancreatic Cancer Cultures","description":"Pancreatic ductal adenocarcinoma (PDAC) is a tumour entity with unmet medical need. To assess the therapeutic potential of oncolytic virotherapy (OVT) against PDAC, different oncolytic viruses (OVs) are currently investigated in clinical trials. However, systematic comparisons of these different OVs in terms of efficacy against PDAC and biomarkers predicting therapeutic response are lacking. We screened fourteen patient-derived PDAC cultures for their sensitivity to five clinically relevant OVs, namely serotype 5 adenovirus Ad5-hTERT, herpes virus T-VEC, measles vaccine strain MV-NIS, reovirus jin-3, and protoparvovirus H 1PV using live cell analysis, quantification of viral genome/gene expression, cell viability as well as cytotoxicity assays. Sensitivity was correlated with transcriptome profiles to identify potential predictive biomarkers for response to OVT. Patient-derived PDAC cultures showed individual response patterns to OV treatment. Twelve of fourteen cultures were responsive to at least one OV, with no single OV proving superior or inferior across all cultures. Known host factors for distinct viruses were retrieved as potential biomarkers. Compared to the basal-like molecular subtype, the quasi-mesenchymal subtype of PDAC was more sensitive to H-1PV, jin-3, and T-VEC. Expression of viral entry receptors did not correlate with sensitivity to OV treatment. Rather, cellular pathways controlling immunological, metabolic, and proliferative signalling appeared to determine outcome. For instance, high baseline expression of interferon-stimulated genes (ISGs) correlated with relative resistance to oncolytic measles virus, whereas cGAS expression was associated with exceptional response. Combination treatment of MV-NIS with a cGAS inhibitor improved tumour cell killing in several PDAC cultures.","abstract":"Pancreatic ductal adenocarcinoma (PDAC) is a tumour entity with unmet medical need. To assess the therapeutic potential of oncolytic virotherapy (OVT) against PDAC, different oncolytic viruses (OVs) are currently investigated in clinical trials. However, systematic comparisons of these different OVs in terms of efficacy against PDAC and biomarkers predicting therapeutic response are lacking. We screened fourteen patient-derived PDAC cultures for their sensitivity to five clinically relevant OVs, namely serotype 5 adenovirus Ad5-hTERT, herpes virus T-VEC, measles vaccine strain MV-NIS, reovirus jin-3, and protoparvovirus H 1PV using live cell analysis, quantification of viral genome/gene expression, cell viability as well as cytotoxicity assays. Sensitivity was correlated with transcriptome profiles to identify potential predictive biomarkers for response to OVT. Patient-derived PDAC cultures showed individual response patterns to OV treatment. Twelve of fourteen cultures were responsive to at least one OV, with no single OV proving superior or inferior across all cultures. Known host factors for distinct viruses were retrieved as potential biomarkers. Compared to the basal-like molecular subtype, the quasi-mesenchymal subtype of PDAC was more sensitive to H-1PV, jin-3, and T-VEC. Expression of viral entry receptors did not correlate with sensitivity to OV treatment. Rather, cellular pathways controlling immunological, metabolic, and proliferative signalling appeared to determine outcome. For instance, high baseline expression of interferon-stimulated genes (ISGs) correlated with relative resistance to oncolytic measles virus, whereas cGAS expression was associated with exceptional response. Combination treatment of MV-NIS with a cGAS inhibitor improved tumour cell killing in several PDAC cultures.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-14T14:44:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007002","title":"Myeloid-specific KDM6B inhibition sensitizes Glioblastoma to PD1 blockade","description":"Glioblastoma (GBM) tumors are enriched in immune-suppressive myeloid cells and are refractory  to immune checkpoint therapy (ICT). Targeting epigenetic pathways to reprogram the functional  phenotype of immune-suppressive myeloid cells to overcome resistance to ICT remains  unexplored. Single-cell and spatial transcriptomic analyses of human GBM tumors demonstrated  high expression of an epigenetic enzyme - histone 3 lysine 27 demethylase (KDM6B) in intra-tumoral immune-suppressive myeloid cell subsets. Importantly, myeloid-cell specific Kdm6b  deletion enhanced pro-inflammatory pathways and improved survival in GBM tumor-bearing  mice. Mechanistic studies elucidated that the absence of Kdm6b enhances antigen-presentation,  interferon response and phagocytosis in myeloid cells by inhibiting mediators of immune  suppression including Mafb, Socs3 and Sirpa. Further, pharmacological inhibition of KDM6B mirrored the functional phenotype of Kdm6b deleted myeloid cells and enhanced anti-PD1 efficacy. Thus, this study identified KDM6B as an epigenetic regulator of the functional phenotype  of myeloid cell subsets and a potential therapeutic target to improve response to ICT.","abstract":"Glioblastoma (GBM) tumors are enriched in immune-suppressive myeloid cells and are refractory  to immune checkpoint therapy (ICT). Targeting epigenetic pathways to reprogram the functional  phenotype of immune-suppressive myeloid cells to overcome resistance to ICT remains  unexplored. Single-cell and spatial transcriptomic analyses of human GBM tumors demonstrated  high expression of an epigenetic enzyme - histone 3 lysine 27 demethylase (KDM6B) in intra-tumoral immune-suppressive myeloid cell subsets. Importantly, myeloid-cell specific Kdm6b  deletion enhanced pro-inflammatory pathways and improved survival in GBM tumor-bearing  mice. Mechanistic studies elucidated that the absence of Kdm6b enhances antigen-presentation,  interferon response and phagocytosis in myeloid cells by inhibiting mediators of immune  suppression including Mafb, Socs3 and Sirpa. Further, pharmacological inhibition of KDM6B mirrored the functional phenotype of Kdm6b deleted myeloid cells and enhanced anti-PD1 efficacy. Thus, this study identified KDM6B as an epigenetic regulator of the functional phenotype  of myeloid cell subsets and a potential therapeutic target to improve response to ICT.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-15T05:14:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007003","title":"Relevance of TMPRSS2, CD163/CD206 and CD33 in clinical severity stratification of COVID-19","description":"Our main objective is to incorporate new markers to classify COVID-19 patients based on mild or severe disease progression. To achieve this, we characterize SNP genotypes in critical genes involved in SARS-CoV infection (ACE2 (rs2285666), MX1 (rs469390), and TMPRSS2 (rs2070788) variants) and study the monocyte population by mass cytometry (CyTOF). Finally, the results obtained will be integrated to search for the best set of predictors of disease aggressiveness.","abstract":"Our main objective is to incorporate new markers to classify COVID-19 patients based on mild or severe disease progression. To achieve this, we characterize SNP genotypes in critical genes involved in SARS-CoV infection (ACE2 (rs2285666), MX1 (rs469390), and TMPRSS2 (rs2070788) variants) and study the monocyte population by mass cytometry (CyTOF). Finally, the results obtained will be integrated to search for the best set of predictors of disease aggressiveness.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-15T12:30:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007004","title":"CAGEKID: Cancer Genomics of the Kidney - Targeted Sequencing","description":"The aim of CAGEKID is to carry out comprehensive detection of DNA markers for conventional (clear cell) renal carcinoma. The project includes complete analysis of somatic and constitutional DNA variation, methylation patterns and expression in a large number of constitutional/tumor pairs. CAGEKID is a part of the International Cancer Genome Consortium, ICGC.","abstract":"The aim of CAGEKID is to carry out comprehensive detection of DNA markers for conventional (clear cell) renal carcinoma. The project includes complete analysis of somatic and constitutional DNA variation, methylation patterns and expression in a large number of constitutional/tumor pairs. CAGEKID is a part of the International Cancer Genome Consortium, ICGC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-15T14:13:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007005","title":"Somatic_mutations_in_the_pancreas__LCM_RE_NanoSeq_","description":"Investigating the mutation burden and mutational signatures in normal and pre-malignant pancreatic tissue.","abstract":"Investigating the mutation burden and mutational signatures in normal and pre-malignant pancreatic tissue.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007006","title":"A machine learning classifier for DNA repair defects using plasma DNA","description":null,"abstract":"We present DARC Sign (DnA Repair Classification SIGNatures); a public machine learning tool leveraging clinically-practical liquid biopsy specimens for simultaneously identifying multiple types of metastatic prostate cancer DDR deficiencies. We posit that it will be useful for understanding differential responses to DDR-directed therapies in ongoing clinical trials and may ultimately enable prospective identification of prostate cancers with phenotypic evidence of DDR deficiency.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-15T17:00:56+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007007","title":"ASXL1 mutations are associated with a response to alvocidib and 5-azacytidine combination in myelodysplastic syndromes","description":null,"abstract":"Inhibitors of anti-apoptotic BCL-2 family proteins in combination with chemotherapy and hypomethylating agents (HMAs) are promising therapeutic approaches in acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS). Alvocidib, a cyclin-dependent kinase 9 (CDK9) inhibitor and indirect transcriptional repressor of the anti-apoptotic factor MCL-1, has previously shown clinical activity in AML. A phase 1b/2 study with alvocidib and HMA 5-Azacytidine (5-AZA) or decitabine in higher-risk patients with MDS has recently tested these substance combinations in this patient group (NCT03593915). Biomarkers for response to the alvocidib + 5-AZA in MDS patients could further improve this treatment concept. In this study, we performed a comprehensive in vitro assessment of alvocidib and 5-AZA effects in a cohort of n=45 high-risk MDS patients. Our data revealed additive cytotoxic effects of the combination treatment. Mutational profiling of MDS samples identified ASXL1 mutations as predictors of response in univariable and multivariable analyses. Further, increased response rates were associated with higher gene-expression of the pro-apoptotic factor NOXA in ASXL1 mutated MDS samples. The higher sensitivity of ASXL1 mutant cells to the alvocidib + 5-AZA treatment was confirmed in vivo in ASXL1Y588X transgenic mice. Overall, our study demonstrated augmented activity for the alvocidib + 5-AZA combination in higher-risk MDS and identified ASXL1 mutations as a biomarker of response for potential stratification studies","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007008","title":"Quantitative analysis of a novel DNA hypermethylation panel for lung cancer diagnosis","description":null,"abstract":"Non-diagnostic findings in Transbronchial Lung Biopsy (TBLB) and Endobronchial Ultrasound-guided Transbronchial Lung Biopsy (EBUS-TBLB) are not uncommon. A challenge is to improve lung cancer detection by TBLB/EBUS-TBLB. In order to improve the diagnostic yield of bronchoscopy, we used 850K methylation chip to identify methylation sites that distinguish malignant from benign lung nodules.We found that the combination of HOXA7, SHOX2,and SCT methylation analysis has the best diagnostic yield in 123 bronchial washing (sensitivity: 74·1%; AUC: 0·851) and 172 brushing samples (sensitivity: 86·1%; AUC: 0·915). We developed a kit comprising these three genes and validated the kit in 329 unique bronchial washing samples, 397 unique brushing samples, and 179 unique patients with both washing and brushing samples. The diagnostic accuracy of the panel alone in lung cancer diagnosis was 86·9%, 91·2% and 95% in bronchial washing, brushing, and washing+brushing samples, respectively. The panel's sensitivity in combination with cytology, rapid on-site evaluation (ROSE), and histology in lung cancer diagnosis was 90·8% and 95.8% in bronchial washing and brushing samples, respectively, and 100% in washing+brushing samples. Quantitative analysis of the three-gene panel improves lung cancer diagnosis by bronchoscopy.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-16T18:01:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007010","title":"Whole exome sequencing in family trios reveals de novo mutations associated to Type 1 Diabetes Mellitus","description":null,"abstract":"This study is to identify de novo mutations in 13 trios from singleton families that contribute to the genetic basis of T1DM through the application of whole-exome sequencing (WES). Our results demonstrate that trio-based WES is a powerful approach for identifying new candidate genes for the pathogenesis of T1D. Genotyping and functional annotation of the discovered de novo variants on a large cohort is recommended to ascertain their association to disease pathogenesis.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007011","title":"Genome wide variation in the Angolan Namib desert reveals unique Pre-Bantu ancestry","description":"The populations of the Angolan Namib Desert have been largely neglected in previous surveys of the genomic landscape of southern Africa. Although at present, the Namib is culturally dominated by Southwest Bantu-speaking cattle-herders, the region exhibits an extraordinary ethnographic diversity which includes an array of semi-nomadic peoples whose subsistence strategies fall outside the traditional division between foraging and food production and can thus be referred to as “peripatetic”. Among these small-scale populations are the last speakers of the Kwadi branch of the Khoe-Kwadi language family associated with the introduction of pastoralism into southern Africa (Kwepe), as well as a range of groups whose origins remain enigmatic (Kwisi, Twa and Tjimba). Using genome-wide data from 208 individuals belonging to nine ethnically diverse groups from the Angolan Namib and adjacent areas (Kwepe, Kwisi, Twa, Tjimba, !Xun, Kuvale, Himba, Nyaneka, Ovimbundu) in combination with published data from other regions of Africa, we reconstruct in detail the histories of contact emerging from pre-historic migrations to southern Africa and show that peripatetic groups from southwestern Angola stand out for exhibiting elevated levels of an unique, regionally-specific and highly divergent Pre-Bantu ancestry. These findings highlight the importance of the Namib for understanding the deep genetic structure of Africa.","abstract":"The populations of the Angolan Namib Desert have been largely neglected in previous surveys of the genomic landscape of southern Africa. Although at present, the Namib is culturally dominated by Southwest Bantu-speaking cattle-herders, the region exhibits an extraordinary ethnographic diversity which includes an array of semi-nomadic peoples whose subsistence strategies fall outside the traditional division between foraging and food production and can thus be referred to as “peripatetic”. Among these small-scale populations are the last speakers of the Kwadi branch of the Khoe-Kwadi language family associated with the introduction of pastoralism into southern Africa (Kwepe), as well as a range of groups whose origins remain enigmatic (Kwisi, Twa and Tjimba). Using genome-wide data from 208 individuals belonging to nine ethnically diverse groups from the Angolan Namib and adjacent areas (Kwepe, Kwisi, Twa, Tjimba, !Xun, Kuvale, Himba, Nyaneka, Ovimbundu) in combination with published data from other regions of Africa, we reconstruct in detail the histories of contact emerging from pre-historic migrations to southern Africa and show that peripatetic groups from southwestern Angola stand out for exhibiting elevated levels of an unique, regionally-specific and highly divergent Pre-Bantu ancestry. These findings highlight the importance of the Namib for understanding the deep genetic structure of Africa.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-17T10:40:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007012","title":"cis-eQTL mapping of TB-T2D comorbidity in a SA cohort","description":"506 samples from the Western Cape, South Africa, were genotyped on the Illumina H3A array (~2.3 M Markers) to discern which ancestry-specific genetic variants are associated with differentially expressed genes in TB-T2D comorbid patients compared to T2D, and in TB patients compared to healthy controls.","abstract":"506 samples from the Western Cape, South Africa, were genotyped on the Illumina H3A array (~2.3 M Markers) to discern which ancestry-specific genetic variants are associated with differentially expressed genes in TB-T2D comorbid patients compared to T2D, and in TB patients compared to healthy controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007013","title":"NEC","description":"This multi-centre, non-randomized, open-label, phase II trial (NCT03016338), assessed niraparib monotherapy (cohort 1, C1), or niraparib and dostarlimab (cohort 2, C2) in patients with recurrent serous or endometrioid endometrial carcinoma. The primary endpoint was clinical benefit rate (CBR). Secondary outcomes were safety and objective response rate (ORR). Translational research was an exploratory outcome. Potential biomarkers were evaluated in archival tissue by immunohistochemistry and next generation sequencing panel. Feasibility of liquid biopsy by ctDNA was assessed.","abstract":"This multi-centre, non-randomized, open-label, phase II trial (NCT03016338), assessed niraparib monotherapy (cohort 1, C1), or niraparib and dostarlimab (cohort 2, C2) in patients with recurrent serous or endometrioid endometrial carcinoma. The primary endpoint was clinical benefit rate (CBR). Secondary outcomes were safety and objective response rate (ORR). Translational research was an exploratory outcome. Potential biomarkers were evaluated in archival tissue by immunohistochemistry and next generation sequencing panel. Feasibility of liquid biopsy by ctDNA was assessed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-17T19:07:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007014","title":"Whole genome, RNA-seq and single-cell Multiome profile of multiple myeloma","description":null,"abstract":"Bispecific antibodies targeting CD3 on T cells and GPRC5D on plasma cells (talquetamab)\ndemonstrate promising efficacy in multiple myeloma. However, disease progression\nfrequently occurs within a year, and the mechanisms of acquired resistance are unknown.\nHere, we use a single-cell multi-omic strategy to explore the mechanisms of talquetamab\nresistance in two patients. In the first patient, a pre-existing 12p deletion encompassing\nGPRC5D locus allowed the emergence of seven resistant subclones at relapse, each\nharboring a distinct second hit leading to the bi-allelic inactivation of the target. In the\nsecond patient, resistant cells displayed a complete loss of GPRC5D expression due to the\nlong-range epigenetic silencing of its promoter and enhancer regions. Thus, acquired\ntalquetamab resistance can result from the genetic or epigenetic inactivation of GPRC5D.\nInvestigating the molecular profiles of target genes may help guiding the choice of\nimmunotherapy and early detection of resistance in multiple myeloma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-20T08:33:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007015","title":"MSI in Lynch syndrome","description":null,"abstract":"Individuals with Lynch syndrome are at increased hereditary risk of colorectal and endometrial carcinomas with microsatellite instability (MSI-H) and mismatch repair-deficiency (dMMR), which make these tumors vulnerable to therapy with immune checkpoint inhibitors. Our aim is to assess how often other tumor types in these individuals share these characteristics. MSI status, somatic second hit alterations and immunohistochemistry-based MMR status were analyzed in 236 non-colorectal (non-CRC) and non-endometrial (non-EC) malignant tumors.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007016","title":"Neuroblastoma heterogeneity","description":"Neuroblastoma is a pediatric solid tumor characterized by strong clinical heterogeneity. Although certain complex genomic alterations, such as extrachromosomal DNA amplifications (ecDNA), are associated with adverse outcomes and have been recurrently detected in neuroblastomas, the mutational processes involved in their generation remain largely unclear. By examining the topography of complex rearrangements along with mutational signatures derived from all variant classes, we identify previously unrecognized co-occurring mutational footprints, which we termed mutational scenarios. We demonstrate that clinical neuroblastoma heterogeneity is linked to differences in the processes driving these mutational scenarios. Whereas high-risk MYCN-amplified neuroblastoma genomes were characterized by signs of replication slippage and stress, homologous recombination-associated signatures defined high-risk non-MYCN-amplified patients. Non-high-risk neuroblastomas, on the other hand, were marked by footprints of chromosome missegregation and TOP1 mutational activity. This analysis provides a systematic perspective on the repertoire of mutational patterns that contribute to clinical neuroblastoma heterogeneity.","abstract":"Neuroblastoma is a pediatric solid tumor characterized by strong clinical heterogeneity. Although certain complex genomic alterations, such as extrachromosomal DNA amplifications (ecDNA), are associated with adverse outcomes and have been recurrently detected in neuroblastomas, the mutational processes involved in their generation remain largely unclear. By examining the topography of complex rearrangements along with mutational signatures derived from all variant classes, we identify previously unrecognized co-occurring mutational footprints, which we termed mutational scenarios. We demonstrate that clinical neuroblastoma heterogeneity is linked to differences in the processes driving these mutational scenarios. Whereas high-risk MYCN-amplified neuroblastoma genomes were characterized by signs of replication slippage and stress, homologous recombination-associated signatures defined high-risk non-MYCN-amplified patients. Non-high-risk neuroblastomas, on the other hand, were marked by footprints of chromosome missegregation and TOP1 mutational activity. This analysis provides a systematic perspective on the repertoire of mutational patterns that contribute to clinical neuroblastoma heterogeneity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-20T09:49:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007017","title":"Epigenome-wide methylation analysis of colorectal carcinoma, adenoma and normal tissue reveals novel biomarkers addressing unmet clinical needs","description":"Studies about CRC biomarker discovery have focused on methylation patterns in normal and colorectal tumor tissue, leading to a lack of knowledge of methylation in adenomas. Therefore, we performed the first epigenome-wide study to compare the epigenomes of all three tissue types combined, and to identify discriminatory biomarkers. Public Illumina MethylEPIC® data was collected from 552 normal, 118 carcinoma and 116 adenoma samples. Pairwise analyses were performed for discovery of differentially methylated probes (DMPs). We identified 693 813, 620 643 and 558 897 DMPs when comparing normal vs carcinoma, normal vs adenoma and adenoma vs carcinoma respectively. To double evidence (DE) these DMPs, analysis of Illumina 450K data from public datasets was performed. Through this analysis, 13 DE DMPs with │Δβ│≥0.3 were identified for adenoma vs carcinoma. A binary logistic regression model was generated to evaluate the discriminatory potential of these DE DMPS. The model was validated in an in-house experimental methylation dataset of 13 adenoma and 9 carcinoma samples. Our classifier reached a cross-validated AUC of 0.996 and 0.855 in the discovery and validation datasets respectively. A sensitivity and specificity of 96% and 95% were reached, with an overall accuracy of 96%. Our analysis show that methylation biomarkers have the potential to discriminate between normal, precursor and carcinoma tissues of the colorectum. More importantly, we highlight the power of the methylome, showing that DMPs can be used as biomarkers in the clinic to identify colorectal adenoma and carcinoma. ","abstract":"Studies about CRC biomarker discovery have focused on methylation patterns in normal and colorectal tumor tissue, leading to a lack of knowledge of methylation in adenomas. Therefore, we performed the first epigenome-wide study to compare the epigenomes of all three tissue types combined, and to identify discriminatory biomarkers. Public Illumina MethylEPIC® data was collected from 552 normal, 118 carcinoma and 116 adenoma samples. Pairwise analyses were performed for discovery of differentially methylated probes (DMPs). We identified 693 813, 620 643 and 558 897 DMPs when comparing normal vs carcinoma, normal vs adenoma and adenoma vs carcinoma respectively. To double evidence (DE) these DMPs, analysis of Illumina 450K data from public datasets was performed. Through this analysis, 13 DE DMPs with │Δβ│≥0.3 were identified for adenoma vs carcinoma. A binary logistic regression model was generated to evaluate the discriminatory potential of these DE DMPS. The model was validated in an in-house experimental methylation dataset of 13 adenoma and 9 carcinoma samples. Our classifier reached a cross-validated AUC of 0.996 and 0.855 in the discovery and validation datasets respectively. A sensitivity and specificity of 96% and 95% were reached, with an overall accuracy of 96%. Our analysis show that methylation biomarkers have the potential to discriminate between normal, precursor and carcinoma tissues of the colorectum. More importantly, we highlight the power of the methylome, showing that DMPs can be used as biomarkers in the clinic to identify colorectal adenoma and carcinoma. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-20T12:59:19+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007018","title":"Circulating tumor DNA of classical Hodgkin lymphoma","description":null,"abstract":"Our study of adult patients with previously untreated cHL aims at: i) identifying subgroups of patients with phenotype- and outcome-associated molecular signatures; ii) testing and validating baseline ctDNA load as a prognostic biomarker; iii) testing if ctDNA can be used for the early identification of chemoresistance.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007019","title":"Neuroblastoma heterogeneity","description":"Neuroblastoma is a pediatric solid tumor characterized by strong clinical heterogeneity. Although certain complex genomic alterations, such as extrachromosomal DNA amplifications (ecDNA), are associated with adverse outcomes and have been recurrently detected in neuroblastomas, the mutational processes involved in their generation remain largely unclear. By examining the topography of complex rearrangements along with mutational signatures derived from all variant classes, we identify previously unrecognized co-occurring mutational footprints, which we termed mutational scenarios. We demonstrate that clinical neuroblastoma heterogeneity is linked to differences in the processes driving these mutational scenarios. Whereas high-risk MYCN-amplified neuroblastoma genomes were characterized by signs of replication slippage and stress, homologous recombination-associated signatures defined high-risk non-MYCN-amplified patients. Non-high-risk neuroblastomas, on the other hand, were marked by footprints of chromosome missegregation and TOP1 mutational activity. This analysis provides a systematic perspective on the repertoire of mutational patterns that contribute to clinical neuroblastoma heterogeneity.","abstract":"Neuroblastoma is a pediatric solid tumor characterized by strong clinical heterogeneity. Although certain complex genomic alterations, such as extrachromosomal DNA amplifications (ecDNA), are associated with adverse outcomes and have been recurrently detected in neuroblastomas, the mutational processes involved in their generation remain largely unclear. By examining the topography of complex rearrangements along with mutational signatures derived from all variant classes, we identify previously unrecognized co-occurring mutational footprints, which we termed mutational scenarios. We demonstrate that clinical neuroblastoma heterogeneity is linked to differences in the processes driving these mutational scenarios. Whereas high-risk MYCN-amplified neuroblastoma genomes were characterized by signs of replication slippage and stress, homologous recombination-associated signatures defined high-risk non-MYCN-amplified patients. Non-high-risk neuroblastomas, on the other hand, were marked by footprints of chromosome missegregation and TOP1 mutational activity. This analysis provides a systematic perspective on the repertoire of mutational patterns that contribute to clinical neuroblastoma heterogeneity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-21T08:29:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007020","title":"X chromosome dosage and the impact on the methylation pattern across human tissues","description":null,"abstract":"Sex chromosome aneuploidies (SCAs) gives rise to a broad range of phenotypic traits and diseases. We performed a comprehensive analysis of X chromosome dosage on the methylome in blood, fat and muscle tissue from individuals with 45,X, 46,XX, 46,XY and 47,XXY","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007021","title":"Single-cell dissection of the immune response after a myocardial infarction","description":null,"abstract":"The immune response plays a pivotal role in initiating cardiac repair and remodeling in both the acute and chronic phase after ST-Elevated myocardial infarction (STEMI). To dissect the longitudinal character of the immune response in STEMI patients over time, we performed single-cell RNA-sequencing (scRNA-seq) on a total of 95,995 peripheral blood mononuclear cells (PBMCs) collected from 38 STEMI patients at hospital admission, 24 hours (acute phase) and 6-8 weeks (chronic phase) after STEMI. Additionally, comparison to healthy controls was performed using previously generated scRNA-seq data on 33,878 PBMCs from 38 age- and sex-matched healthy controls from the Dutch population cohort Lifelines DEEP.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-21T15:19:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007022","title":"Covid19 RNAseq Fastq files","description":"RNA Sequencing using Illumina’s TruSeq Stranded Total RNA with RiboZero Globin depletion library pre-kit and sequencing on the NovaSeq 6000.","abstract":"RNA Sequencing using Illumina’s TruSeq Stranded Total RNA with RiboZero Globin depletion library pre-kit and sequencing on the NovaSeq 6000.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-21T17:20:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007023","title":"Integrated single cell analysis in transformed follicular lymphoma","description":"Histological transformation of follicular lymphoma to aggressive form occurs 2-3% per year with poor outcome. Divergent evolution and an altered tumour-microenvironment (TME) have been implicated during transformation. However, phenotypic consequences of this evolution and its implication in TME remain unknown. To address this, we performed single cell whole genome and whole transcriptome sequencing of paired pre/post transformation patient samples. We further performed scWTS of additional samples from patients without transformation. Our analysis revealed evolutionary dynamics of transformation at unprecedented resolution. Integration of scWGS and scWTS identified pathways upregulated during evolution. scWTS analysis revealed a shifting TME landscape, with an exhausted signature emerging during transformation. Using multi-color immunofluorescence we transferred these findings to a TME-based transformation biomarker, subsequently validated in independent pretreatment cohorts. Taken together, our results provide a comprehensive view of the combined genomic and phenotypic evolution of malignant cells during transformation, and shifting cross-talk between malignant cells and TME.","abstract":"Histological transformation of follicular lymphoma to aggressive form occurs 2-3% per year with poor outcome. Divergent evolution and an altered tumour-microenvironment (TME) have been implicated during transformation. However, phenotypic consequences of this evolution and its implication in TME remain unknown. To address this, we performed single cell whole genome and whole transcriptome sequencing of paired pre/post transformation patient samples. We further performed scWTS of additional samples from patients without transformation. Our analysis revealed evolutionary dynamics of transformation at unprecedented resolution. Integration of scWGS and scWTS identified pathways upregulated during evolution. scWTS analysis revealed a shifting TME landscape, with an exhausted signature emerging during transformation. Using multi-color immunofluorescence we transferred these findings to a TME-based transformation biomarker, subsequently validated in independent pretreatment cohorts. Taken together, our results provide a comprehensive view of the combined genomic and phenotypic evolution of malignant cells during transformation, and shifting cross-talk between malignant cells and TME.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-21T19:36:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007024","title":"RNAseq analysis on metastasis-derived organoids (LMO)","description":null,"abstract":"Bank of metastasis-derived organoids (LMO)","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-22T15:55:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007025","title":"Shot-gun stool metagenomics and colorectal cancer risk.","description":"This study aims to identify metagenomics biomarkers in colorectal cancer (CRC). The study includes 156 samples of shot-gun stool metagenomics, corresponding to 51 patients with CRC, 54 patients with high-risk adenoma, and 51 healthy controls. The sequencing libraries were prepared with 2 µg of total DNA using the Nextera XT DN Sample Prep Kit (Illumina, San Diego, CA, USA). Sequencing was performed at 150 nucleotides, paired-end, using an Illumina HiSeq 4000 platform.","abstract":"This study aims to identify metagenomics biomarkers in colorectal cancer (CRC). The study includes 156 samples of shot-gun stool metagenomics, corresponding to 51 patients with CRC, 54 patients with high-risk adenoma, and 51 healthy controls. The sequencing libraries were prepared with 2 µg of total DNA using the Nextera XT DN Sample Prep Kit (Illumina, San Diego, CA, USA). Sequencing was performed at 150 nucleotides, paired-end, using an Illumina HiSeq 4000 platform.","study_type":"Other","pubmed_ids":[36077748],"external_links":null,"is_released":true,"released_date":"2023-02-22T16:19:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007026","title":"Parallel sequencing of extrachromosomal circular DNAs and transcriptomes in single cancer cells","description":null,"abstract":"Oncogenic extrachromosomal DNAs (ecDNA) are common in cancers, but many questions about their origin, structural dynamics and impact on intratumor heterogeneity are still unresolved. Here we describe scEC&amp;T-seq, a method for parallel isolation and sequencing of extrachromosomal circular DNAs and full-length mRNA from single human cells. By applying scEC&amp;T-seq to cancer cells, we not only describe intercellular differences in ecDNA content, but also investigate their structural heterogeneity and transcriptional impact. We reveal that whereas oncogene-containing ecDNA elements are clonally present in cancer cells and drive intercellular oncogene expression differences, other small circular DNAs also captured by scEC&amp;T-seq are mostly private to individual cancer cells, indicating differences in selection and propagation. Moreover, scEC&amp;T-seq uncovers intercellular differences in ecDNA structure, which allowed the inference of ecDNA structural dynamics and point to circular recombination as a potential mechanism of ecDNA evolution. We envision that our method may enable the analysis of yet unknown prerequisites for the maintenance of both small and large circular DNA in cancers, but also in the context of other diseases and normal cellular development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-22T16:36:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007027","title":"Reconstruction of the personal information from human genome reads in gut metagenome sequencing data","description":"Human DNA present in fecal samples can result in a small number of human reads in gut shotgun metagenomic sequencing data. However, it is currently unclear how much personal information can be reconstructed from such reads and this has not been quantitatively evaluated. Such a quantitative evaluation is necessary to clarify the ethical concerns related to data sharing and to enable the efficient use of human genetic information in stool samples, such as for research and forensics. Here, we used genomic approaches to reconstruct personal information from fecal metagenomes of 343 Japanese individuals with associated human genotype data. Our approach can be used to quantify the personal information contained within gut metagenome data.","abstract":"Human DNA present in fecal samples can result in a small number of human reads in gut shotgun metagenomic sequencing data. However, it is currently unclear how much personal information can be reconstructed from such reads and this has not been quantitatively evaluated. Such a quantitative evaluation is necessary to clarify the ethical concerns related to data sharing and to enable the efficient use of human genetic information in stool samples, such as for research and forensics. Here, we used genomic approaches to reconstruct personal information from fecal metagenomes of 343 Japanese individuals with associated human genotype data. Our approach can be used to quantify the personal information contained within gut metagenome data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-23T02:05:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007028","title":"Ribosomal depleted RNA-Sequencing data of fetal astrocytes derived from TSC and VWM","description":null,"abstract":"Astrocytes are critical in development and everyday function. Astrocytopathies, diseases which are characterized by the deterioration or dysfunction of astrocytes, such as Tuberous Sclerosis Complex (TSC) and Vanishing White Matter (VWM), are often associated with neurological impairment and can be fatal. Reactive astrocytes can be proinflammatory and neurotoxic, states which are enhanced when exposed to the inflammatory cytokine IL1ß and the reactive oxidative species (ROS), such as H2O2. We investigated the transcriptomic perturbations during cellular stress in vitro in astrocytes derived from TSC and VWM. Both the linear and circular RNA (circRNA) profiles were investigated in this study.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007029","title":"A novel transcriptional signature identifies T-cell infiltration in high-risk paediatric cancer","description":"Background\nMolecular profiling of the tumour immune microenvironment (TIME) has enabled the rational choice of immunotherapies in some adult cancers. In contrast, the TIME of paediatric cancers is relatively unexplored. We speculated that a more refined appreciation of the TIME in childhood cancers, rather than a reliance on commonly used biomarkers such as tumour mutation burden (TMB), neoantigen load and PD-L1 expression, is an essential prerequisite for improved immunotherapies in childhood solid cancers.\nMethods\nWe combined immunohistochemistry (IHC) with RNA-sequencing and whole genome sequencing across a diverse spectrum of high-risk paediatric cancers to develop an alternative, expression-based signature associated with CD8+ T-cell infiltration of the TIME. Further, we explored transcriptional features of immune archetypes, T-cell receptor sequencing diversity, assessed the relationship between CD8+ and CD4+ abundance by IHC and deconvolution predictions, and assessed common adult biomarkers such as neoantigen load and TMB.\nResults\nA novel 15-gene immune signature, Immune Paediatric Signature Score (IPASS), was identified. Using this signature, we estimate up to 31% of high-risk cancers harbour infiltrating T-cells. In addition, we showed that PD-L1 protein expression is poorly correlated with PD-L1 RNA expression and TMB and neoantigen load are not predictive of T-cell infiltration in paediatrics. Furthermore, deconvolution algorithms are only weakly correlated with IHC measurements of T-cells.\nConclusions\nOur data provides new insights into the variable immune-suppressive mechanisms dampening responses in paediatric solid cancers. Effective immune-based interventions in\nhigh-risk paediatric cancer will require individualised analysis of the TIME.","abstract":"Background\nMolecular profiling of the tumour immune microenvironment (TIME) has enabled the rational choice of immunotherapies in some adult cancers. In contrast, the TIME of paediatric cancers is relatively unexplored. We speculated that a more refined appreciation of the TIME in childhood cancers, rather than a reliance on commonly used biomarkers such as tumour mutation burden (TMB), neoantigen load and PD-L1 expression, is an essential prerequisite for improved immunotherapies in childhood solid cancers.\nMethods\nWe combined immunohistochemistry (IHC) with RNA-sequencing and whole genome sequencing across a diverse spectrum of high-risk paediatric cancers to develop an alternative, expression-based signature associated with CD8+ T-cell infiltration of the TIME. Further, we explored transcriptional features of immune archetypes, T-cell receptor sequencing diversity, assessed the relationship between CD8+ and CD4+ abundance by IHC and deconvolution predictions, and assessed common adult biomarkers such as neoantigen load and TMB.\nResults\nA novel 15-gene immune signature, Immune Paediatric Signature Score (IPASS), was identified. Using this signature, we estimate up to 31% of high-risk cancers harbour infiltrating T-cells. In addition, we showed that PD-L1 protein expression is poorly correlated with PD-L1 RNA expression and TMB and neoantigen load are not predictive of T-cell infiltration in paediatrics. Furthermore, deconvolution algorithms are only weakly correlated with IHC measurements of T-cells.\nConclusions\nOur data provides new insights into the variable immune-suppressive mechanisms dampening responses in paediatric solid cancers. Effective immune-based interventions in\nhigh-risk paediatric cancer will require individualised analysis of the TIME.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-24T02:56:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007030","title":"Targeted sequence of MDS cases treated with azacitidine","description":null,"abstract":"This is a study in which clonal changes of driver genes were examined by sequencing marrow and blood samples before and after azacitidine treatment for myelodysplastic syndromes and related diseases. This archive is a set of bam files analyzed in this study.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007031","title":"Spatial transcriptomic paired treatment naive and residual HGSOC","description":null,"abstract":"Single cell analysis and spatial transcriptomics reveal that the content in the ECM-producing ANTXR1+ CAF-S1 cluster (ECM-myCAF) decreases the most after chemotherapy in HGSOC. Moreover, functional assays using ECM-myCAF from HGSOC demonstrate for the first time that ECM-myCAF reduce CD8+ T cell cytotoxicity through a Yes Associated Protein 1 (YAP1)-dependent mechanism. Thus, chemotherapy inhibits YAP1-signaling pathway in ECM-myCAF, which promotes CD8+ T lymphocyte re-infiltration and paves the way to new therapy in HGSOC","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007032","title":"scRNAseq CAF HGSOC","description":"Single cell analysis and spatial transcriptomics reveal that the content in the ECM-producing ANTXR1+ CAF-S1 cluster (ECM-myCAF) decreases the most after chemotherapy in HGSOC. Moreover, functional assays using ECM-myCAF from HGSOC demonstrate for the first time that ECM-myCAF reduce CD8+ T cell cytotoxicity through a Yes Associated Protein 1 (YAP1)-dependent mechanism. Thus, chemotherapy inhibits YAP1-signaling pathway in ECM-myCAF, which promotes CD8+ T lymphocyte re-infiltration and paves the way to new therapy in HGSOC","abstract":"Single cell analysis and spatial transcriptomics reveal that the content in the ECM-producing ANTXR1+ CAF-S1 cluster (ECM-myCAF) decreases the most after chemotherapy in HGSOC. Moreover, functional assays using ECM-myCAF from HGSOC demonstrate for the first time that ECM-myCAF reduce CD8+ T cell cytotoxicity through a Yes Associated Protein 1 (YAP1)-dependent mechanism. Thus, chemotherapy inhibits YAP1-signaling pathway in ECM-myCAF, which promotes CD8+ T lymphocyte re-infiltration and paves the way to new therapy in HGSOC","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007033","title":"A PROSTATE TUMORGRAFT PANEL TO ACCELERATE PRECISION MEDICINE","description":"The management of advanced prostate cancer (PCa) has strongly evolved in the last decade with the introduction of the next generation of androgen receptor pathway inhibitors which have considerably improved patient outcomes. Most recently, the investigation of genomic landscape has provided targetable molecular alterations such as homologous gene DNA repair defects correlated with response to PARP inhibitors. Despite these significant advances, while localized PCa is generally associated with favorable outcome, metastatic PCa is currently considered incurable. For further investigations in precision treatment, the development of preclinical models representing the complex prostate tumor heterogeneity are mandatory. Accordingly, we aimed to establish a resource of patient-derived xenograft (PDX) models that exemplify each phase of this multistage disease for accurate and rapid evaluation of candidate therapies.","abstract":"The management of advanced prostate cancer (PCa) has strongly evolved in the last decade with the introduction of the next generation of androgen receptor pathway inhibitors which have considerably improved patient outcomes. Most recently, the investigation of genomic landscape has provided targetable molecular alterations such as homologous gene DNA repair defects correlated with response to PARP inhibitors. Despite these significant advances, while localized PCa is generally associated with favorable outcome, metastatic PCa is currently considered incurable. For further investigations in precision treatment, the development of preclinical models representing the complex prostate tumor heterogeneity are mandatory. Accordingly, we aimed to establish a resource of patient-derived xenograft (PDX) models that exemplify each phase of this multistage disease for accurate and rapid evaluation of candidate therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-24T13:57:37+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007034","title":"Clonal_dynamics_and_mutation_burden_in_male_germline___WES__TubulesOxford_","description":"This work aims to study clonal dynamics of pathogenic mutations in male germline using exome NanoSeq of sections of seminiferous tubules from tissue donors. An exome panel will be used to achieve high coverage across coding regions to interrogate known and novel drivers.","abstract":"Little is known about mutagenesis within the hierarchy of spermatogenesis or factors that influence rates of mutation in the testes/sperm. It is likely that mutations in spermatogonia stem cells that confer weaker selective advantage and generate smaller clonal expansions in the testes, become enrich in sperms and transmit to the next generations. However, due to the low sensitivity of standard genomic approaches, subclonal mutations that may only be present in small contiguous areas within testes have been poorly investigated.\n\nThis proposal aims to investigate the mutational landscape in seminiferous tubules.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007035","title":"Single cell epigenomic study of H3-K27M mutant diffuse midline glioma across age and location","description":"Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in childhood diffuse midline gliomas (DMGs) of the pons, but are also increasingly recognized in adult DMGs. Their potential heterogeneity at different ages and midline locations are vastly understudied. Here, through dissecting the single-cell epigenomic architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We analyzed the open chromatin profiles of 8 tumors utilizing the single-cell/nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq)","abstract":"Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in childhood diffuse midline gliomas (DMGs) of the pons, but are also increasingly recognized in adult DMGs. Their potential heterogeneity at different ages and midline locations are vastly understudied. Here, through dissecting the single-cell epigenomic architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We analyzed the open chromatin profiles of 8 tumors utilizing the single-cell/nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-24T17:54:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007036","title":"Whole-genome sequencing across 449 samples spanning 47 ethnolinguistic groups provides insights into genetic diversity in Nigeria","description":"African populations have been drastically underrepresented in genomics research and failure to capture the genetic diversity across the numerous ethnolinguistic groups (ELGs) found in the continent has hindered the equity of precision medicine initiatives globally. Here, we describe the whole-genome sequencing of 449 Nigerian individuals across 47 unique self-reported ELGs. Population structure analysis reveals genetic differentiation amongst our ELGs, consistent with previous findings. From the 36 million SNPs and indels discovered in our dataset, we provide a high-level catalog of both novel and medically-relevant variation present across the ELGs. These results emphasize the value of this resource for genomics research, with added granularity by representing multiple ELGs from Nigeria. Our results also underscore the potential of using these cohorts with larger sample sizes to improve our understanding of human ancestry and health in Africa.","abstract":"African populations have been drastically underrepresented in genomics research and failure to capture the genetic diversity across the numerous ethnolinguistic groups (ELGs) found in the continent has hindered the equity of precision medicine initiatives globally. Here, we describe the whole-genome sequencing of 449 Nigerian individuals across 47 unique self-reported ELGs. Population structure analysis reveals genetic differentiation amongst our ELGs, consistent with previous findings. From the 36 million SNPs and indels discovered in our dataset, we provide a high-level catalog of both novel and medically-relevant variation present across the ELGs. These results emphasize the value of this resource for genomics research, with added granularity by representing multiple ELGs from Nigeria. Our results also underscore the potential of using these cohorts with larger sample sizes to improve our understanding of human ancestry and health in Africa.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-24T18:31:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007037","title":"AG Test Case","description":"Bar","abstract":"Bar","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007038","title":"An IL-1β driven neutrophil-stromal cell axis fosters a BAFF-rich microenvironment in multiple myeloma","description":"The bone marrow is continuously occupied by high numbers of neutrophils, and a tumor-supportive bias of these cells could significantly impact bone marrow-confined malignancies. In multiple myeloma, the bone marrow is characterized by inflammatory stromal cells with the potential to influence neutrophils. Here, we investigated myeloma-associated alterations in marrow neutrophils and the impact of stromal inflammation on neutrophil function. Mature neutrophils in myeloma marrow are activated and tumor-supportive, transcribing increased levels of pro-inflammatory cytokines, including IL-1β, and myeloma cell survival factors, such as the BCMA-ligand BAFF. Neutrophils were re-activated after first-line treatment, while this regimen reduced, but did not normalize, stromal inflammation. Interactions with inflammatory stroma induced neutrophil activation, including BAFF secretion, in a STAT3-dependent manner and once activated, neutrophils gained the ability to reciprocally induce stromal activation. Combined, our data define the presence of a neutrophil-stromal cell feed-forward loop driving tumor-supportive inflammation that could impact disease recurrence.","abstract":"The bone marrow is continuously occupied by high numbers of neutrophils, and a tumor-supportive bias of these cells could significantly impact bone marrow-confined malignancies. In multiple myeloma, the bone marrow is characterized by inflammatory stromal cells with the potential to influence neutrophils. Here, we investigated myeloma-associated alterations in marrow neutrophils and the impact of stromal inflammation on neutrophil function. Mature neutrophils in myeloma marrow are activated and tumor-supportive, transcribing increased levels of pro-inflammatory cytokines, including IL-1β, and myeloma cell survival factors, such as the BCMA-ligand BAFF. Neutrophils were re-activated after first-line treatment, while this regimen reduced, but did not normalize, stromal inflammation. Interactions with inflammatory stroma induced neutrophil activation, including BAFF secretion, in a STAT3-dependent manner and once activated, neutrophils gained the ability to reciprocally induce stromal activation. Combined, our data define the presence of a neutrophil-stromal cell feed-forward loop driving tumor-supportive inflammation that could impact disease recurrence.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-26T17:53:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007039","title":"Molecular features of adenomas predicting metachronous colorectal cancer: a nested-case control study","description":"\"Background &amp; Aims: Current morphological features defining advanced adenomas (size ≥10 mm, high grade dysplasia or &gt;25% villous component) cannot optimally distinguish individuals at high-risk or low-risk of metachronous colorectal cancer (me-CRC), which may result in suboptimal surveillance. Certain DNA copy number alterations are associated with adenoma-to-carcinoma progression (cancer-associated events; CAEs). We aimed to evaluate whether CAEs can better predict an individual’s risk of me-CRC than the morphological advanced adenoma features. \nMethods: In this nested case-control study, 529 individuals with a single adenoma at their first colonoscopy were selected from a Norwegian adenoma cohort. DNA copy number profiles were determined, by means of low-coverage whole genome sequencing. We assessed the prevalence of CAEs in advanced and non-advanced adenomas and its association with me-CRC. For the latter, cases (with CRC) were matched to controls (without CRC), with the same follow-up period as cases, as well as age and sex. Subsequently, odds ratios (OR) for the association of the presence of an advanced adenoma or a molecularly-defined high-risk adenoma with me-CRC were calculated. \nResults: Molecular high-risk features were observed in 85/267 (32%) of advanced adenomas and in 27/262 (10%) of non-advanced adenomas. Me-CRC was more strongly associated with advanced adenomas (OR 3.58; 95% CI 2.27-5.72) than with molecular high-risk adenomas (OR 1.90; 95% CI 1.14–3.16). After adjusting for other variables, only advanced adenoma remained significantly associated with me-CRC (OR 3.39; 95% CI 2.10–5.55).\nConclusion:  Molecularly-defined high-risk adenomas were associated with me-CRC, but the association of advanced adenoma with me-CRC was stronger. \"\n\nProject goal: Evaluate the value of DNA copy numbers alterations detected in  a baseline adenoma, in the prediction of risk of metachronous CRC","abstract":"\"Background &amp; Aims: Current morphological features defining advanced adenomas (size ≥10 mm, high grade dysplasia or &gt;25% villous component) cannot optimally distinguish individuals at high-risk or low-risk of metachronous colorectal cancer (me-CRC), which may result in suboptimal surveillance. Certain DNA copy number alterations are associated with adenoma-to-carcinoma progression (cancer-associated events; CAEs). We aimed to evaluate whether CAEs can better predict an individual’s risk of me-CRC than the morphological advanced adenoma features. \nMethods: In this nested case-control study, 529 individuals with a single adenoma at their first colonoscopy were selected from a Norwegian adenoma cohort. DNA copy number profiles were determined, by means of low-coverage whole genome sequencing. We assessed the prevalence of CAEs in advanced and non-advanced adenomas and its association with me-CRC. For the latter, cases (with CRC) were matched to controls (without CRC), with the same follow-up period as cases, as well as age and sex. Subsequently, odds ratios (OR) for the association of the presence of an advanced adenoma or a molecularly-defined high-risk adenoma with me-CRC were calculated. \nResults: Molecular high-risk features were observed in 85/267 (32%) of advanced adenomas and in 27/262 (10%) of non-advanced adenomas. Me-CRC was more strongly associated with advanced adenomas (OR 3.58; 95% CI 2.27-5.72) than with molecular high-risk adenomas (OR 1.90; 95% CI 1.14–3.16). After adjusting for other variables, only advanced adenoma remained significantly associated with me-CRC (OR 3.39; 95% CI 2.10–5.55).\nConclusion:  Molecularly-defined high-risk adenomas were associated with me-CRC, but the association of advanced adenoma with me-CRC was stronger. \"\n\nProject goal: Evaluate the value of DNA copy numbers alterations detected in  a baseline adenoma, in the prediction of risk of metachronous CRC","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-27T09:04:35+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007040","title":"Targeted_NanoSeq_ccRCC_Pilot","description":"Targeted NanoSeq of ccRCC tumours to determine their subclonal diversity.","abstract":"Pilot project to identify subclonal diversity of clear cell renal cell carcinoma tumours.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007041","title":"IMI-RHAPSODY data","description":"Molecular data of large diabetes cohorts was generated to identify markers of diabetes progression measured as time to insulin initiation","abstract":"Molecular data of large diabetes cohorts was generated to identify markers of diabetes progression measured as time to insulin initiation","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-27T11:11:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007042","title":"Methylation-based classification of human mesenchymal chondrosarcoma","description":"We applied methylome and copy number profiling to a set of 45 well characterized MCS cases to evaluate their potential diagnostic value. Notably, the findings were reproducible also when analysing the round cell and cartilaginous component separately. Furthermore, four outliers were identified by methylome profiling for which the diagnosis had to be revised. Methylome profiling represents a sensitive, specific and reliable tool to support the diagnosis of MCS, particularly if only the round cell component is obtained in a biopsy and the diagnosis is not suspected. It can furthermore aid in confirming the diagnosis in case RNA sequencing for the HEY1::NCOA2 fusion transcript is not available.","abstract":"We applied methylome and copy number profiling to a set of 45 well characterized MCS cases to evaluate their potential diagnostic value. Notably, the findings were reproducible also when analysing the round cell and cartilaginous component separately. Furthermore, four outliers were identified by methylome profiling for which the diagnosis had to be revised. Methylome profiling represents a sensitive, specific and reliable tool to support the diagnosis of MCS, particularly if only the round cell component is obtained in a biopsy and the diagnosis is not suspected. It can furthermore aid in confirming the diagnosis in case RNA sequencing for the HEY1::NCOA2 fusion transcript is not available.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-27T14:42:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007043","title":"Gtag&T single-cell genome and transcriptome data","description":"This submission contains single-cell genome and transcriptome data that is used for the following manuscript: https://doi.org/10.1101/2023.01.13.521174. All Illumina data deposited here is retrieved from HCC38(BL) cell lines and a melanoma PDX model as described in the paper.","abstract":"This submission contains single-cell genome and transcriptome data that is used for the following manuscript: https://doi.org/10.1101/2023.01.13.521174. All Illumina data deposited here is retrieved from HCC38(BL) cell lines and a melanoma PDX model as described in the paper.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-27T14:57:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007044","title":"Single-cell RNA-seq of cervix and placenta","description":"Placental trophoblasts have been detected in cervical smears early in gestation, creating opportunities for non-invasive prenatal diagnosis. However, trophoblast isolation is limited by the lack of a cell catalogue and molecular profile of cervical smears. To establish an atlas and to explore the potential of single-cell RNA-sequencing to detect cervical trophoblasts, 10,539 single-cell transcriptomes from 12 non-invasive exocervical smears from pregnant women were profiled. In addition, we characterized 34,565 cells from six placental biopsies. We uncovered a novel extravillous trophoblast cell subtype characterized by epithelial marker genes and reduced HLA-G expression. Integration of both cell atlases demonstrated surprisingly similar expression profiles between maternal epithelial cells and placental extravillous trophoblasts, indicating that these trophoblasts retained epithelial properties without an invasive mesenchymal phenotype. Additionally, differential expression analysis identified novel markers discriminating cervical and placental cell types. Those analyses may contribute to trophoblast discovery and isolation from cervical smears.","abstract":"Placental trophoblasts have been detected in cervical smears early in gestation, creating opportunities for non-invasive prenatal diagnosis. However, trophoblast isolation is limited by the lack of a cell catalogue and molecular profile of cervical smears. To establish an atlas and to explore the potential of single-cell RNA-sequencing to detect cervical trophoblasts, 10,539 single-cell transcriptomes from 12 non-invasive exocervical smears from pregnant women were profiled. In addition, we characterized 34,565 cells from six placental biopsies. We uncovered a novel extravillous trophoblast cell subtype characterized by epithelial marker genes and reduced HLA-G expression. Integration of both cell atlases demonstrated surprisingly similar expression profiles between maternal epithelial cells and placental extravillous trophoblasts, indicating that these trophoblasts retained epithelial properties without an invasive mesenchymal phenotype. Additionally, differential expression analysis identified novel markers discriminating cervical and placental cell types. Those analyses may contribute to trophoblast discovery and isolation from cervical smears.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-27T15:31:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007045","title":"Germline genome sequencing samples from the Hereditary Cancer Syndromes (ICCon) Cancer Flagship","description":"A prospective study of individuals with suspicion of a hereditary cancer syndrome for whom previous clinical targeted genetic testing was either not informative or was not available. To identify pathogenic disease-causing variants explaining participant presentation, germline whole-genome sequencing and a comprehensive cancer virtual gene panel analysis were undertaken.","abstract":"A prospective study of individuals with suspicion of a hereditary cancer syndrome for whom previous clinical targeted genetic testing was either not informative or was not available. To identify pathogenic disease-causing variants explaining participant presentation, germline whole-genome sequencing and a comprehensive cancer virtual gene panel analysis were undertaken.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-02-28T05:42:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007046","title":"HG_TP10518_SLE_MAP_WGS","description":"This project aims to build a sc-eQTL map from PBMCs from 300 SLE patients and 200 healthy volunteers, stimulated with three types of stimuli and profiled at two time points.","abstract":"Systemic Lupus Erythematosus (SLE) is an debilitating autoimmune condition and the development of novel therapies for SLE has been challenging. The aim of this study is to use sc-RNA-Seq to understand the functional effect of key genetic variants that have been associated with the disease. We will use  transcriptome profiling to generate a single cell eQTL map of gene expression regulation in PBMCs from individuals with SLE.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007047","title":"VRK3 depletion in Pontine Diffuse Midline Glioma (DMG)-K27 altered cells","description":null,"abstract":"In order to investigate possible mechanisms underlying the phenotype of cell fitness decline observed following decrease of VRK3 in pontine DMG-K27 altered cells 7, we examined differences in global gene expression. RNA-seq was performed 44h and 60h post-transduction with two distinct shRNAs targeting VRK3 to be able to evaluate the early impact of VRK3 knock-down (KD) in four independent in vitro models of DMG","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-01T10:32:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007048","title":"Covid19 WGS BAM files","description":"The Samples were collected from Saint James's Hospital, Dublin, and after informed consent Extracted Genomic DNA samples were prepared and sequenced using the Automated Illumina TruSeq PCR-free methodology.","abstract":"The Samples were collected from Saint James's Hospital, Dublin, and after informed consent Extracted Genomic DNA samples were prepared and sequenced using the Automated Illumina TruSeq PCR-free methodology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-01T10:59:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007049","title":"Genome-wide DNA Copy Number Analysis of high hyperdiploid acute lymphoblastic leukemia","description":null,"abstract":"This dataset included samples with high hyperdiploid acute lymphoblastic leukemia (ALL) that were collected from four different cohorts: the Division of Clinical Genetics, Lund University, Sweden. All samples were genotyped using Affymetrix SNP Array or Illumina's BeadArray platform. This dataset has been used for copy number aberrations analysis for high hyperdiploid ALL.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-01T12:09:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007050","title":"Covid19 RNAseq BAM files","description":"RNA Sequencing using Illumina’s TruSeq Stranded Total RNA with RiboZero Globin depletion library pre-kit and sequencing on the NovaSeq 6000.","abstract":"RNA Sequencing using Illumina’s TruSeq Stranded Total RNA with RiboZero Globin depletion library pre-kit and sequencing on the NovaSeq 6000.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-01T14:21:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007051","title":"RNAseq analysis on primary sites Colorectal Cancer xenografts (PRX) samples","description":null,"abstract":"Bank of primary sites (PRs) colorectal cancer of Patient Derived Xenografts (PDXs)","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-02T09:05:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007052","title":"Timing chromosomal amplification events using patterns of somatic mutations in high hyperdiploid acute lymphoblastic leukemia","description":"This dataset included samples with high hyperdiploid acute lymphoblastic leukemia (ALL) collected from the Division of Clinical Genetics, Lund University, Sweden. All samples were subjected to whole genome sequencing using the Illumina HiSeqX platform. Paired-end sequencing (2x150bp) was done to ~60x coverage for diagnostic samples and ~30x coverage for remission samples. The paired-end reads were aligned to the human reference genome GRCh37 (https://www.ncbi.nlm.nih.gov/assembly/GCF_000001405.25/) by the Burrows-Wheeler Aligner tool (version 0.7.17). Duplicate reads marking and local realignment were performed by GATK (version 4.0.11.0).","abstract":"This dataset included samples with high hyperdiploid acute lymphoblastic leukemia (ALL) collected from the Division of Clinical Genetics, Lund University, Sweden. All samples were subjected to whole genome sequencing using the Illumina HiSeqX platform. Paired-end sequencing (2x150bp) was done to ~60x coverage for diagnostic samples and ~30x coverage for remission samples. The paired-end reads were aligned to the human reference genome GRCh37 (https://www.ncbi.nlm.nih.gov/assembly/GCF_000001405.25/) by the Burrows-Wheeler Aligner tool (version 0.7.17). Duplicate reads marking and local realignment were performed by GATK (version 4.0.11.0).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-02T13:19:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007053","title":"Whole genome and whole exome sequencing of serial biopsies of relapsed/refractory diffuse large B-cell lymphoma.","description":"Purpose: Diffuse large B-cell lymphoma (DLBCL) is cured in more than 60% of patients, but outcomes remain poor for patients experiencing disease progression or relapse (refractory or relapsed DLBCL [rrDLBCL]), particularly if these events occur early. Although previous studies examining cohorts of rrDLBCL have identified features that are enriched at relapse, few have directly compared serial biopsies to uncover biological and evolutionary dynamics driving rrDLBCL. Here, we sought to confirm the relationship between relapse timing and outcomes after second-line (immuno)chemotherapy and determine the evolutionary dynamics that underpin that relationship.\n\nPatients and methods: Outcomes were examined in a population-based cohort of 221 patients with DLBCL who experienced progression/relapse after frontline treatment and were treated with second-line (immuno)chemotherapy with an intention-to-treat with autologous stem-cell transplantation (ASCT). Serial DLBCL biopsies from a partially overlapping cohort of 129 patients underwent molecular characterization, including whole-genome or whole-exome sequencing in 73 patients.\n\nResults: Outcomes to second-line therapy and ASCT are superior for late relapse (&gt;2 years postdiagnosis) versus primary refractory (&lt;9 months) or early relapse (9-24 months). Diagnostic and relapse biopsies were mostly concordant for cell-of-origin classification and genetics-based subgroup. Despite this concordance, the number of mutations exclusive to each biopsy increased with time since diagnosis, and late relapses shared few mutations with their diagnostic counterpart, demonstrating a branching evolution pattern. In patients with highly divergent tumors, many of the same genes acquired new mutations independently in each tumor, suggesting that the earliest mutations in a shared precursor cell constrain tumor evolution toward the same genetics-based subgroups at both diagnosis and relapse.\n\nConclusion: These results suggest that late relapses commonly represent genetically distinct and chemotherapy-naïve disease and have implications for optimal patient management.","abstract":"Purpose: Diffuse large B-cell lymphoma (DLBCL) is cured in more than 60% of patients, but outcomes remain poor for patients experiencing disease progression or relapse (refractory or relapsed DLBCL [rrDLBCL]), particularly if these events occur early. Although previous studies examining cohorts of rrDLBCL have identified features that are enriched at relapse, few have directly compared serial biopsies to uncover biological and evolutionary dynamics driving rrDLBCL. Here, we sought to confirm the relationship between relapse timing and outcomes after second-line (immuno)chemotherapy and determine the evolutionary dynamics that underpin that relationship.\n\nPatients and methods: Outcomes were examined in a population-based cohort of 221 patients with DLBCL who experienced progression/relapse after frontline treatment and were treated with second-line (immuno)chemotherapy with an intention-to-treat with autologous stem-cell transplantation (ASCT). Serial DLBCL biopsies from a partially overlapping cohort of 129 patients underwent molecular characterization, including whole-genome or whole-exome sequencing in 73 patients.\n\nResults: Outcomes to second-line therapy and ASCT are superior for late relapse (&gt;2 years postdiagnosis) versus primary refractory (&lt;9 months) or early relapse (9-24 months). Diagnostic and relapse biopsies were mostly concordant for cell-of-origin classification and genetics-based subgroup. Despite this concordance, the number of mutations exclusive to each biopsy increased with time since diagnosis, and late relapses shared few mutations with their diagnostic counterpart, demonstrating a branching evolution pattern. In patients with highly divergent tumors, many of the same genes acquired new mutations independently in each tumor, suggesting that the earliest mutations in a shared precursor cell constrain tumor evolution toward the same genetics-based subgroups at both diagnosis and relapse.\n\nConclusion: These results suggest that late relapses commonly represent genetically distinct and chemotherapy-naïve disease and have implications for optimal patient management.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-02T17:53:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007054","title":"PhIP-Seq data","description":"Inflammatory bowel diseases (IBD), e.g. Crohn’s disease (CD) and ulcerative colitis\n(UC), are chronic immune-mediated inflammatory diseases. A comprehensive\noverview of an IBD-specific antibody epitope repertoire is, however, lacking. We\nleveraged a high-throughput phage-displayed immunoprecipitation sequencing\n(PhIP-seq) workflow to identify antibodies against 344,000 antimicrobial, immune and\nfood antigens in 497 IBD patients.","abstract":"Inflammatory bowel diseases (IBD), e.g. Crohn’s disease (CD) and ulcerative colitis\n(UC), are chronic immune-mediated inflammatory diseases. A comprehensive\noverview of an IBD-specific antibody epitope repertoire is, however, lacking. We\nleveraged a high-throughput phage-displayed immunoprecipitation sequencing\n(PhIP-seq) workflow to identify antibodies against 344,000 antimicrobial, immune and\nfood antigens in 497 IBD patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-03T12:29:34+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007055","title":"Single cell RNA-seq from AD and PS patients","description":"We applied single cell immune profiling to gain a holistic view from immune cells infiltrating the skin to circulating immune cells, facilitating a better understanding of the two diseases in their entirety, and the identification of potential type-2 or type-3-disease-driving mechanisms.","abstract":"We applied single cell immune profiling to gain a holistic view from immune cells infiltrating the skin to circulating immune cells, facilitating a better understanding of the two diseases in their entirety, and the identification of potential type-2 or type-3-disease-driving mechanisms.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-06T07:49:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007056","title":"Mitochondrial_DNA_copy_number_of_haematopoietic_cells__foetal__WGS","description":"Low coverage WGS (likely as low as 0.5X or below) could theorretically be used to infer the average mitochondrial copy number per cell of normal diploid cells. This will be applied to homogenous populations of haematopoietic stem cells and progenitors at different points during development/ adult life. In this study we will only look at foetal samples.","abstract":"Well-functioning mitochondria are of vital importance to maintaining haematopoietic stem cell function.  Understanding the number of copies of the mitochondrial DNA genome - and related to this, the number of mitochondria - is therefore of importance to understanding how mitochondrial copy number is maintained and regulated through life and different stages of haematopoietic differentiation.  This may also inform interpretation of mitochondrial DNA copy number estimates fom single-cell derived colonies that have undergone differentiation.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007057","title":"Ultrasensitive detection of minor allele fractions in maternal samples based on microhaplotype analysis","description":"Background: Tools for quantifying and studying genetic variation in heterogeneous cell populations have a limited sensitivity. However, many biological problems require ultrasensitive genetic deconvolution of cell mixtures. The detection of fetal cells in cervical samples from pregnant women presents such a challenge.\nMethods: Using deep sequencing of microhaplotype loci and analysis of the error profiles in genetically pure and mixed samples, we increase the sensitivity for minor allele detection and demonstrate the potential for paternal allele detection in cervical samples from pregnant women. \nResults: Using artificial DNA mixtures, we show that unique alleles can be readily identified in mixtures with a ratio of 1 in 10,000 (0.01%). By applying this method on ten non-invasive cervical samples from pregnant women we could identify the presence of paternal alleles in half of the samples. Unexpectedly, we demonstrate those alleles not to be of fetal origin but of sperm. \nConclusions: We developed a novel method that can deconvolute genetic mixtures to at least 0.01%, which can be applied to study minor allele fractions in genetic mixtures and, for example, could aid in trophoblast cell detection in maternal blood or cervix. Our results demonstrate the importance of discriminating fetal and paternal alleles when analyzing cervical fetal cells and may pinpoint a potential cause of erroneous results in previous trophoblast isolation studies.","abstract":"Background: Tools for quantifying and studying genetic variation in heterogeneous cell populations have a limited sensitivity. However, many biological problems require ultrasensitive genetic deconvolution of cell mixtures. The detection of fetal cells in cervical samples from pregnant women presents such a challenge.\nMethods: Using deep sequencing of microhaplotype loci and analysis of the error profiles in genetically pure and mixed samples, we increase the sensitivity for minor allele detection and demonstrate the potential for paternal allele detection in cervical samples from pregnant women. \nResults: Using artificial DNA mixtures, we show that unique alleles can be readily identified in mixtures with a ratio of 1 in 10,000 (0.01%). By applying this method on ten non-invasive cervical samples from pregnant women we could identify the presence of paternal alleles in half of the samples. Unexpectedly, we demonstrate those alleles not to be of fetal origin but of sperm. \nConclusions: We developed a novel method that can deconvolute genetic mixtures to at least 0.01%, which can be applied to study minor allele fractions in genetic mixtures and, for example, could aid in trophoblast cell detection in maternal blood or cervix. Our results demonstrate the importance of discriminating fetal and paternal alleles when analyzing cervical fetal cells and may pinpoint a potential cause of erroneous results in previous trophoblast isolation studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-06T16:24:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007058","title":"cis-eQTL mapping of TB-T2D comorbidity in SA cohort","description":null,"abstract":"The validation of genome-wide association signals for tuberculosis (TB) susceptibility as well as the development of type 2 diabetes (T2D) across diverse populations are ongoing challenges. In addition, the ancestry-specific variants (coding and non-coding) that contribute to previously identified differentially expressed genes (DEG) in patients with TB, T2D and comorbid TB-T2D, remain unknown. Identifying ancestry-specific expression quantitative trait loci (eQTLs) can aid in distinguishing the most probable disease-causing variants for population-specific therapeutic interventions. Therefore, this study conducted cis-eQTL mapping in TB, T2D and TB-T2D patients to identify variants associated with DEG. Both genotyping (Infinium H3A array with ~2.3 M markers) and RNA sequencing data of 96 complex multi-way admixed South Africans were used for this purpose. Importantly, both global-and local ancestry adjustment were included in statistical analysis to account for complex admixture. Unique gene-variant pairs were associated with TB-T2D on chromosome 7p22 whilst adjusting for Bantu-speaking African ancestry (PRKAR1B:rs4464850; P=7.68e-07) and Khoe-San ancestry (PRKAR1B:rs117842122; P=3.66e-07). In addition, IFITM3 (a biomarker for the development of TB) was associated with three eSNPs (rs11025530, rs3808990, and rs10896664) on chromosome 11p15 while adjusting for Khoe-San ancestry. Our results also indicated that the upregulation of the NLRP6 inflammasome is strongly associated with people with TB-T2D while adjusting for Khoe-San ancestry. Three African-specific eGenes (NLRP6, IFITM3 and PRKAR1B) would have been missed if local ancestry adjustment was not conducted. This study determined a list of ancestry-specific eQTLs in TB-T2D patients that could potentially guide the search for new therapeutic targets for TB-T2D in African populations.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007059","title":"cis-eQTL mapping of TB-T2D comorbidity in a five-way admixed SA cohort","description":"The aim of the study was to identify ancestry-specific genetic variants associated with differentially expressed genes in TB-T2D comorbid patients compared to T2D patients, as well as between TB patients and healthy controls. Both global and local ancestry was incorporated in regression models to account for the genetic heterogeneity in our complex multi-way admixed population.","abstract":"The aim of the study was to identify ancestry-specific genetic variants associated with differentially expressed genes in TB-T2D comorbid patients compared to T2D patients, as well as between TB patients and healthy controls. Both global and local ancestry was incorporated in regression models to account for the genetic heterogeneity in our complex multi-way admixed population.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-08T08:47:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007060","title":"RNA sequencing data of 257 samples from 106 patients with HR+/HER2- breast cancer treated with AC plus paclitaxel or letrozole plus ribociclib (SOLTI-1402 CORALLEEN trial)","description":"Early-stage Luminal B breast cancer is frequent and is a major cause of breast cancer death due to its poor prognosis. Our proposal aims to study the biology behind the sensitivity and resistance of Luminal B breast cancer to chemotherapy (CHT) or a non-CHT regimen composed of hormone therapy in combination with ribociclib, a CDK4/6 inhibitor. To accomplish this, we first completed the SOLTI-1402 CORALLEEN phase II trial, a study where 106 patients with early-stage Luminal B breast cancer were randomized to standard neoadjuvant CHT for 6 months, or neoadjuvant letrozole and ribociclib for 6 months. After treatment, patients underwent surgery. The primary results of the study, which showed that the response rate to letrozole+ribociclib was similar to CHT, was reported (Prat et al; Lancet Oncol). Tumor biopsies were available at baseline, week 3 and surgery. A total of 257 samples were analyzed using the Illumina TruSeq Stranded Total RNA w/Ribo Zero Gold with MiSeq in TGL (Sequencer NovaSeq S4/PE/100x).","abstract":"Early-stage Luminal B breast cancer is frequent and is a major cause of breast cancer death due to its poor prognosis. Our proposal aims to study the biology behind the sensitivity and resistance of Luminal B breast cancer to chemotherapy (CHT) or a non-CHT regimen composed of hormone therapy in combination with ribociclib, a CDK4/6 inhibitor. To accomplish this, we first completed the SOLTI-1402 CORALLEEN phase II trial, a study where 106 patients with early-stage Luminal B breast cancer were randomized to standard neoadjuvant CHT for 6 months, or neoadjuvant letrozole and ribociclib for 6 months. After treatment, patients underwent surgery. The primary results of the study, which showed that the response rate to letrozole+ribociclib was similar to CHT, was reported (Prat et al; Lancet Oncol). Tumor biopsies were available at baseline, week 3 and surgery. A total of 257 samples were analyzed using the Illumina TruSeq Stranded Total RNA w/Ribo Zero Gold with MiSeq in TGL (Sequencer NovaSeq S4/PE/100x).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-08T12:09:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007061","title":"Germline whole genome sequencing of patients with Li-Fraumeni syndrome","description":"Five hundred ng to 1 ug of genomic DNA was submitted to The Centre for Applied Genomics (TCAG) at The Hospital for Sick Children for genomic library preparation and whole genome sequencing. DNA samples were quantified using the Qubit High Sensitivity Assay and purity was assessed using the Nanodrop OD 260/280 ratio. Approximately 500-700 ng of DNA was used as input material for library preparation using the Illumina TruSeq PCR-free DNA Library Prep Kit following the manufacturer’s recommended protocol. In brief, DNA was fragmented to 400 bp on average using sonication on a Covaris LE220 instrument. Fragmented DNA was end-repaired, A-tailed and indexed TruSeq Illumina adapters with overhang-T were added to the DNA. Libraries were then validated on a Bioanalyzer DNA High Sensitivity chip to check for size and absence of primer dimers and quantified by qPCR using Kapa Library Quantification Illumina/ABI Prism Kit protocol (KAPA Biosystems). Validated libraries were pooled in equimolar quantities and paired-end sequenced on an Illumina HiSeq X platform following Illumina’s recommended protocol to generate paired-end reads of 150-bases in length and an average depth of 40X. FASTQ files were aligned to the hg19 reference genome using BWA-mem v0.78. PCR duplicates were marked with Picard MarkDuplicates v1.1.08, and base recalibration and realignment was performed using GATK v2.8.1.","abstract":"Five hundred ng to 1 ug of genomic DNA was submitted to The Centre for Applied Genomics (TCAG) at The Hospital for Sick Children for genomic library preparation and whole genome sequencing. DNA samples were quantified using the Qubit High Sensitivity Assay and purity was assessed using the Nanodrop OD 260/280 ratio. Approximately 500-700 ng of DNA was used as input material for library preparation using the Illumina TruSeq PCR-free DNA Library Prep Kit following the manufacturer’s recommended protocol. In brief, DNA was fragmented to 400 bp on average using sonication on a Covaris LE220 instrument. Fragmented DNA was end-repaired, A-tailed and indexed TruSeq Illumina adapters with overhang-T were added to the DNA. Libraries were then validated on a Bioanalyzer DNA High Sensitivity chip to check for size and absence of primer dimers and quantified by qPCR using Kapa Library Quantification Illumina/ABI Prism Kit protocol (KAPA Biosystems). Validated libraries were pooled in equimolar quantities and paired-end sequenced on an Illumina HiSeq X platform following Illumina’s recommended protocol to generate paired-end reads of 150-bases in length and an average depth of 40X. FASTQ files were aligned to the hg19 reference genome using BWA-mem v0.78. PCR duplicates were marked with Picard MarkDuplicates v1.1.08, and base recalibration and realignment was performed using GATK v2.8.1.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-08T23:31:51+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007062","title":"Spatiotemporal Genomic Profiling of Intestinal Metaplasia Reveals Clonal Dynamics of Gastric Cancer Progression","description":null,"abstract":"Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa\nassociated with increased gastric cancer (GC) risk. We analyzed &gt;1200 gastric\nsamples (1152 IMs) from &gt;690 subjects from a 10-year prospective study. We\nidentified 26 IM driver genes in diverse pathways including chromatin regulation\n(ARID1A) and intestinal homeostasis (SOX9), largely occurring as subclonal events.\nAnalysis of clonal dynamics between and within subjects, and also longitudinally\nacross time, revealed that IM clones are likely transient but increase in size upon\nprogression to dysplasia, with eventual transmission of genetic events to paired\nGCs. Single-cell and spatial profiling highlighted changes in tissue ecology and\nlineage heterogeneity in IM, including an intestinal stem-cell dominant cellular\ncompartment linked to early malignancy. Expanded transcriptome profiling revealed\nexpression-based molecular subtypes of IM, including a body-resident\n“pseudoantralized” subtype associated with incomplete histology, antral/intestinal cell\ntypes, ARID1A mutations, inflammation, and microbial communities normally\nassociated with the healthy oral tract. We demonstrate that combined clinic-genomic\nmodels outperform clinical-only models in predicting IMs likely to progress. By\nhighlighting strategies for accurately identifying IM patients at high GC risk and a role\nfor microbial dysbiosis in IM progression, our results raise opportunities for GC\nprecision prevention and interception.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007063","title":"Whole_Genome_Landscape_in_Breast","description":"LCM whole genome sequencing of healthy and cancerous breast tissue","abstract":"Investigating age-associated methylation patterns in healthy and cancerous breast tissue","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007064","title":"Linked-read based analysis of Medulloblastomas","description":"Medulloblastoma (MB) is the most common type of malignant pediatric brain tumor with group 4 medulloblastomas (G4 MBs) accounting for 40% of cases of medulloblastomas.  The molecular mechanisms that underlie this subgroup are still poorly understood. Point mutations are detected in a large number of genes at low incidence per gene while the detection of complex structural variants (SVs) in recurrently affected gene typically requires the application of long-read technologies. Here, we applied linked-read sequencing, which combines the long-range genome information of long-read sequencing with the high base pair accuracy of short read sequencing and very low sample input requirements.","abstract":"Medulloblastoma (MB) is the most common type of malignant pediatric brain tumor with group 4 medulloblastomas (G4 MBs) accounting for 40% of cases of medulloblastomas.  The molecular mechanisms that underlie this subgroup are still poorly understood. Point mutations are detected in a large number of genes at low incidence per gene while the detection of complex structural variants (SVs) in recurrently affected gene typically requires the application of long-read technologies. Here, we applied linked-read sequencing, which combines the long-range genome information of long-read sequencing with the high base pair accuracy of short read sequencing and very low sample input requirements.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-10T14:26:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007065","title":"Single-cell multiomic atlas of human retinal organoid development","description":null,"abstract":"In order to provide multi-omic resolution to human retinal organoid developmental dynamics, we performed scRNA-seq and scATAC-seq from the same cell suspension across a time course (6-46 weeks) of human retinal organoid development. We also performed scMultiome experiments on the same cells at week-15 and week-36. This data set covers all the retinal organoid single-cell genomic data generated from the 01F49i-N-B7 (B7) cell line.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007066","title":"Genomic determinants of therapy response in ETV6-RUNX1 leukemia","description":null,"abstract":"ETV6-RUNX1 (E::R) subgroup is the second most frequent form of B cell acute lymphoblastic leukemia (B-ALL) in childhood. This subgroup of ALL generally presents with low-risk features and responds well to chemotherapy with ensuing favorable prognosis. Some patients, however, have a slow response to induction treatment and carry increased risk for relapse. The aim of this study is to identify genetic differences between E::R cases stratified by MRD (NOPHO ALL2008 protocol), and to identify potential mediators of poor therapy response.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-10T17:11:53+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007067","title":"Spatiotemporal Genomic Profiling of Intestinal Metaplasia Reveals Clonal Dynamics of Gastric Cancer Progression","description":"Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We analyzed 1256 gastric samples (1152 IMs) from 692 subjects from a 10-year prospective study. We identified 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9), largely occurring as subclonal events. Analysis of clonal dynamics between and within subjects, and also longitudinally across time, revealed that IM clones are likely transient but increase in size upon progression to dysplasia, with eventual transmission of genetic events to paired GCs. Single-cell and spatial profiling highlighted changes in tissue ecology and lineage heterogeneity in IM, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling revealed expression-based molecular subtypes of IM, including a body-resident “pseudoantralized” subtype associated with incomplete histology, antral/intestinal cell types, ARID1A mutations, inflammation, and microbial communities normally associated with the healthy oral tract. We demonstrate that combined clinical-genomic models outperform clinical-only models in predicting IMs likely to progress. Our results raise opportunities for GC precision prevention and interception by highlighting strategies for accurately identifying IM patients at high GC risk and a role for microbial dysbiosis in IM progression.","abstract":"Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We analyzed 1256 gastric samples (1152 IMs) from 692 subjects from a 10-year prospective study. We identified 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9), largely occurring as subclonal events. Analysis of clonal dynamics between and within subjects, and also longitudinally across time, revealed that IM clones are likely transient but increase in size upon progression to dysplasia, with eventual transmission of genetic events to paired GCs. Single-cell and spatial profiling highlighted changes in tissue ecology and lineage heterogeneity in IM, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling revealed expression-based molecular subtypes of IM, including a body-resident “pseudoantralized” subtype associated with incomplete histology, antral/intestinal cell types, ARID1A mutations, inflammation, and microbial communities normally associated with the healthy oral tract. We demonstrate that combined clinical-genomic models outperform clinical-only models in predicting IMs likely to progress. Our results raise opportunities for GC precision prevention and interception by highlighting strategies for accurately identifying IM patients at high GC risk and a role for microbial dysbiosis in IM progression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-11T11:07:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007068","title":"-","description":"-","abstract":"-","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007069","title":"test","description":null,"abstract":"test","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007070","title":"RNA-seq of PDAC patient-derived xenograft tumors","description":null,"abstract":"We developed a novel antibody-drug conjugate (ADC), C6-EBET. To analyze mechanism of action of C6-EBET, we obtained bulk and single cell RNA-seq data of two patient-derived xenograft (PDX) models derived from pancreatic ductal adenocarcinoma (PDAC) patients. The two PDX models were treated with gemcitabine, C6-EBET or a non-targeting control ADC (HEL3-EBET), and then gene expression changes were analyzed with bulk RNA-seq. In addition, we characterized stromal cells of the two PDX models with scRNA-seq.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-13T01:25:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007071","title":"cfDNAme allows early prediction of PE","description":"Preeclampsia (PE) is a leading cause for peripartal morbidity, especially if developing early in gestation. To enable prophylaxis to prevent PE, it is essential that pregnancies at risk of PE are identified early, in the first trimester. To identify patients at risk, we profiled methylomes of plasma-derived cell-free DNA (cfDNA) from pregnant women. We detected DNA methylation differences between control and PE pregnancies that enable risk stratification of patients, at PE diagnosis but also presymptomatically, around 12 weeks of gestation.","abstract":"Preeclampsia (PE) is a leading cause for peripartal morbidity, especially if developing early in gestation. To enable prophylaxis to prevent PE, it is essential that pregnancies at risk of PE are identified early, in the first trimester. To identify patients at risk, we profiled methylomes of plasma-derived cell-free DNA (cfDNA) from pregnant women. We detected DNA methylation differences between control and PE pregnancies that enable risk stratification of patients, at PE diagnosis but also presymptomatically, around 12 weeks of gestation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-13T06:58:36+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007072","title":"LOGGIC Core BioClinical Data Bank: Added clinical value of RNA-Seq in an international molecular diagnostic registry for pediatric low-grade glioma patients","description":null,"abstract":"The international, multicenter registry LOGGIC Core BioClinical Data Bank aims to enhance the understanding of tumor biology in pediatric low-grade glioma (pLGG) and provide clinical and molecular data to support treatment decisions and interventional trial participation. Hence, the question arises whether implementation of RNA sequencing (RNA-Seq) using Fresh Frozen (FrFr) tumor tissue in addition to gene panel and DNA methylation analysis improves diagnostic accuracy and provides additional clinical benefit. RNA-Seq was performed on 125 of the samples for which FrFr tumor tissue was available. We confirmed KIAA1549::BRAF-fusion (n=71), BRAF V600E-mutation (n=12) and alterations in FGFR1 (n=14) as the most frequent alterations, among other common molecular drivers (n=12). . N=16 cases (13%) presented rare gene fusions (e.g. TPM3::NTRK1, EWSR1::VGLL1, SH3PXD2A::HTRA1, PDGFB::LRP1, GOPC::ROS1). In n=27 cases (22%), RNA-Seq detected a driver alteration not otherwise identified (22/27 actionable). The rate of driver alteration detection was hereby increased from 75% to 97%. Furthermore, FGFR1 ITD (n=6) were only detected by RNA-Seq using current bioinformatics pipelines, leading to a change in analysis protocols.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-13T09:11:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007073","title":"Modelling_structural_variants_in_disease","description":"Oxford nanopore long read sequencing (ideally 20-30 kb reads) of two monoclonal HEK293T cell lines that have ~ 200 copies of recombinase sites (loxP) inserted in repetitive elements throughout the genome. There will be four samples. Two are uninduced and two are induced with the Cre recombinase. We wish to identify the number and location of all loxP sites in the uninduced samples and characterise the genomic rearrangements arising from Cre recombination in the induced samples","abstract":"We have cell lines with ~ 200 loxP sites integrated in repetitive LINE1 elements. We wish to reconstruct the genome of these cell lines and map the location and exact number of the loxP sites. Then we will introduce rearrangements in the cell lines by induction with the Cre recombinase. We will follow up on the structural variants generated by long read sequencing","study_type":"Synthetic Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007074","title":"Clonally resolved single-cell multi-omics identifies routes of cellular differentiation in actue myeloid leukemia","description":null,"abstract":"Single-cell whole transcriptome and surface marker expression was generated for 24 samples of 19 AML patients and a healthy reference sample. Libraries to increase the coverage of the mitochondrial genome and selected nuclear variants were obtained following a protocol termed Optimized 10x. Exome sequencing was performed on 15 patients to identify nuclear variants. To discover mitochondrial variants, bulk ATAC was carried out in 9 patients. MutaSeq (a modified version of SmartSeq2) was performed on 3 samples of cohort A. Targeted DNA sequencing of single-cell derived colonies was generated for one patient.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007075","title":"DNA methylation of peripheral blood leukocytes from patients with Li-Fraumeni syndrome","description":"Genomic DNA (~ 1 μg) from LFS patients was treated using sodium bisulfite (Qiagen) converting unmethylated cytosine to uracil but leaving methylated cytosine intact. These samples were then hybridized to the HumanMethylation450 BeadChip or HumanMethylationEPIC BeadChip from Illumina at the Centre for Applied Genomics (TCAG) at the Hospital for Sick Children using the manufacturer’s recommended protocol.","abstract":"Genomic DNA (~ 1 μg) from LFS patients was treated using sodium bisulfite (Qiagen) converting unmethylated cytosine to uracil but leaving methylated cytosine intact. These samples were then hybridized to the HumanMethylation450 BeadChip or HumanMethylationEPIC BeadChip from Illumina at the Centre for Applied Genomics (TCAG) at the Hospital for Sick Children using the manufacturer’s recommended protocol.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-13T14:54:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007076","title":"Treatment stratification and biomarker validation using patient-derived head and neck cancer organoids","description":"Background\nOrganoids are three-dimensional structures that can be grown from patient-derived material including carcinomas. These in vitro models can be cryopreserved to generate “living” biobanks that reflect patient heterogeneity. Head and neck cancer (HNC) is a collective term used for tumors arising in the head and neck area, including squamous cell carcinomas (HNSCC) and adenocarcinoma of the salivary gland. Methods to culture patient-derived HNC organoids have previously been described. \nMethods\nOrganoids were derived from resection or biopsy material of patients included between 2016 and 2022. Organoids were characterised with immunohistochemistry and whole exome sequencing (WES) and exposed to chemo-, radio- and targeted-therapies. CRISPR/Cas9-based gene editing was applied to validate proposed biomarkers. \nResults \nWe have extended our previously published organoid biobank to a total of 110 organoid models, some of which were characterised by histology and WES. Organoids recapitulated both single nucleotide variants and copy number alterations as found in patient HNSCC samples. Organoid and patient response to radiotherapy (RT; primary (n=6) and adjuvant (n=15)) could be compared in 21 HNC cases. In the adjuvant RT group, organoids derived from patients that relapsed were more resistant to RT in vitro, showing potential for guiding treatment options in this subset of patients. \nConclusion\nTaken together, these results indicate illustrate the potential of organoids as a diagnostic tool in personalised medicine for HNC and indicate the potential of this technology for biomarker discovery and validation within the context of relevant patient heterogeneity.","abstract":"Background\nOrganoids are three-dimensional structures that can be grown from patient-derived material including carcinomas. These in vitro models can be cryopreserved to generate “living” biobanks that reflect patient heterogeneity. Head and neck cancer (HNC) is a collective term used for tumors arising in the head and neck area, including squamous cell carcinomas (HNSCC) and adenocarcinoma of the salivary gland. Methods to culture patient-derived HNC organoids have previously been described. \nMethods\nOrganoids were derived from resection or biopsy material of patients included between 2016 and 2022. Organoids were characterised with immunohistochemistry and whole exome sequencing (WES) and exposed to chemo-, radio- and targeted-therapies. CRISPR/Cas9-based gene editing was applied to validate proposed biomarkers. \nResults \nWe have extended our previously published organoid biobank to a total of 110 organoid models, some of which were characterised by histology and WES. Organoids recapitulated both single nucleotide variants and copy number alterations as found in patient HNSCC samples. Organoid and patient response to radiotherapy (RT; primary (n=6) and adjuvant (n=15)) could be compared in 21 HNC cases. In the adjuvant RT group, organoids derived from patients that relapsed were more resistant to RT in vitro, showing potential for guiding treatment options in this subset of patients. \nConclusion\nTaken together, these results indicate illustrate the potential of organoids as a diagnostic tool in personalised medicine for HNC and indicate the potential of this technology for biomarker discovery and validation within the context of relevant patient heterogeneity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-14T09:18:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007077","title":"ACT-Discover: identifying karyotype heterogeneity in pancreatic cancer evolution using ctDNA","description":"Background\nLiquid biopsies, and the dynamic tracking of somatic mutations within circulating tumour DNA (ctDNA) can provide insight into the dynamics of cancer evolution and the intra-tumour heterogeneity that fuels treatment resistance. However, identifying and tracking dynamic changes in somatic copy-number alterations (SCNAs), which have been associated with poor outcome and metastasis, using ctDNA is challenging. Pancreatic adenocarcinoma is a disease which has been considered to harbour early punctuated events in its evolution, leading to an early fitness peak, with minimal further subclonal evolution.\n\nMethods\nTo interrogate the role of SCNAs in pancreatic adenocarcinoma cancer evolution, we applied whole-exome sequencing of 55 longitudinal cell-free DNA (cfDNA) samples taken from 24 patients (including 8 from whom a patient-derived xenograft (PDX) was derived) with metastatic disease prospectively recruited into a clinical trial. We developed a method, Aneuploidy in Circulating Tumour DNA (ACT-Discover), that leverages haplotype phasing of paired tumour biopsies or PDXs to identify SCNAs in cfDNA with greater sensitivity. \n\nResults \nSCNAs were observed within 28 of 47 evaluable cfDNA samples. Of these events, 30% could only be identified by harnessing the haplotype-aware approach leveraged in ACT-Discover. The exceptional purity of PDX tumours enabled near-complete phasing of genomic regions in allelic imbalance, highlighting an important auxiliary function of PDXs. Finally, although the classical model of pancreatic cancer evolution emphasises the importance of early, homogenous somatic events as a key requirement for cancer development, ACT-Discover identified substantial heterogeneity of SCNAs, including parallel focal and arm-level events, affecting different parental alleles within individual tumours. Indeed, ongoing acquisition of SCNAs was identified within tumours throughout the disease course, including within an untreated metastatic tumour. \n\nConclusions \nThis work demonstrates the power of haplotype phasing to study genomic variation in cfDNA samples and reveals undiscovered intra-tumour heterogeneity with important scientific and clinical implications. Implementation of ACT-Discover could lead to important insights from existing cohorts, or underpin future prospective studies seeking to characterise the landscape of tumour evolution through liquid biopsy.","abstract":"Background\nLiquid biopsies, and the dynamic tracking of somatic mutations within circulating tumour DNA (ctDNA) can provide insight into the dynamics of cancer evolution and the intra-tumour heterogeneity that fuels treatment resistance. However, identifying and tracking dynamic changes in somatic copy-number alterations (SCNAs), which have been associated with poor outcome and metastasis, using ctDNA is challenging. Pancreatic adenocarcinoma is a disease which has been considered to harbour early punctuated events in its evolution, leading to an early fitness peak, with minimal further subclonal evolution.\n\nMethods\nTo interrogate the role of SCNAs in pancreatic adenocarcinoma cancer evolution, we applied whole-exome sequencing of 55 longitudinal cell-free DNA (cfDNA) samples taken from 24 patients (including 8 from whom a patient-derived xenograft (PDX) was derived) with metastatic disease prospectively recruited into a clinical trial. We developed a method, Aneuploidy in Circulating Tumour DNA (ACT-Discover), that leverages haplotype phasing of paired tumour biopsies or PDXs to identify SCNAs in cfDNA with greater sensitivity. \n\nResults \nSCNAs were observed within 28 of 47 evaluable cfDNA samples. Of these events, 30% could only be identified by harnessing the haplotype-aware approach leveraged in ACT-Discover. The exceptional purity of PDX tumours enabled near-complete phasing of genomic regions in allelic imbalance, highlighting an important auxiliary function of PDXs. Finally, although the classical model of pancreatic cancer evolution emphasises the importance of early, homogenous somatic events as a key requirement for cancer development, ACT-Discover identified substantial heterogeneity of SCNAs, including parallel focal and arm-level events, affecting different parental alleles within individual tumours. Indeed, ongoing acquisition of SCNAs was identified within tumours throughout the disease course, including within an untreated metastatic tumour. \n\nConclusions \nThis work demonstrates the power of haplotype phasing to study genomic variation in cfDNA samples and reveals undiscovered intra-tumour heterogeneity with important scientific and clinical implications. Implementation of ACT-Discover could lead to important insights from existing cohorts, or underpin future prospective studies seeking to characterise the landscape of tumour evolution through liquid biopsy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-14T09:52:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007078","title":"Clonally resolved single-cell multi-omics identifies routes of cellular differentiation in acute myeloid leukemia","description":"In this study we generated single-cell whole transcriptome and surface marker expression data for 24 samples of 19 AML patients as well as one healthy donor. We followed the CITEseq protocol with the 3' 10x Genomics scRNAseq kit version 3.1 To increase the coverage of the mitochondrial genome we generated mitochondrial libraries following a protocol termed Optimized 10x. Based on TAPseq, we generated libraries to increase the coverage of selected nuclear SNVs. Exome sequencing was generated for 15 patients to identify nuclear variants. Bulk ATAC was obtained for 9 samples to facilitate the discovery of mitochondrial SNVs. MutaSeq (modified version of SmartsSeq2) was performed on cells from 3 patients. Targeted DNAseq from single-cell derived colonies was generated for 1 patient.","abstract":"In this study we generated single-cell whole transcriptome and surface marker expression data for 24 samples of 19 AML patients as well as one healthy donor. We followed the CITEseq protocol with the 3' 10x Genomics scRNAseq kit version 3.1 To increase the coverage of the mitochondrial genome we generated mitochondrial libraries following a protocol termed Optimized 10x. Based on TAPseq, we generated libraries to increase the coverage of selected nuclear SNVs. Exome sequencing was generated for 15 patients to identify nuclear variants. Bulk ATAC was obtained for 9 samples to facilitate the discovery of mitochondrial SNVs. MutaSeq (modified version of SmartsSeq2) was performed on cells from 3 patients. Targeted DNAseq from single-cell derived colonies was generated for 1 patient.","study_type":"Other","pubmed_ids":[37098346],"external_links":null,"is_released":true,"released_date":"2023-03-14T11:34:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007079","title":"Transgenerational transmission of reproductive and metabolic dysfunction in the male progeny of polycystic ovary syndrome","description":"The transgenerational maternal effects of PCOS in female progeny have been revealed. As there are evidence that a male equivalent of PCOS may exist, we asked whether sons born to mother with PCOS (PCOS-sons) transmit reproductive and metabolic phenotypes to their male progeny. Here, in a Swedish nationwide register-based cohort and a clinical case-control study from Chile we found that PCOS-sons are more often obese and dyslipidemic. Their serum miRNAs are found to potentially regulate PCOS-risk genes. Our prenatal androgenized PCOS-like mouse model with or without diet-induced obesity confirmed that reproductive and metabolic dysfunctions in F1 male offspring are passed down to F3. Small non-coding RNAs (sncRNAs) sequencing of F1-F3 sperm revealed distinct differentially expressed (DE) sncRNAs across generations in the androgenized, obese, and obese and androgenized lineages, respectively. Notably, common targets between transgenerational DEsncRNAs in mouse sperm and in PCOS-sons serum indicate similar effects of maternal hyperandrogenism. These findings strengthen the translational relevance highlighting a previously underappreciated risk of reproductive and metabolic dysfunction via the male germline transmission and potential molecular markers to study in future generations.","abstract":"The transgenerational maternal effects of PCOS in female progeny have been revealed. As there are evidence that a male equivalent of PCOS may exist, we asked whether sons born to mother with PCOS (PCOS-sons) transmit reproductive and metabolic phenotypes to their male progeny. Here, in a Swedish nationwide register-based cohort and a clinical case-control study from Chile we found that PCOS-sons are more often obese and dyslipidemic. Their serum miRNAs are found to potentially regulate PCOS-risk genes. Our prenatal androgenized PCOS-like mouse model with or without diet-induced obesity confirmed that reproductive and metabolic dysfunctions in F1 male offspring are passed down to F3. Small non-coding RNAs (sncRNAs) sequencing of F1-F3 sperm revealed distinct differentially expressed (DE) sncRNAs across generations in the androgenized, obese, and obese and androgenized lineages, respectively. Notably, common targets between transgenerational DEsncRNAs in mouse sperm and in PCOS-sons serum indicate similar effects of maternal hyperandrogenism. These findings strengthen the translational relevance highlighting a previously underappreciated risk of reproductive and metabolic dysfunction via the male germline transmission and potential molecular markers to study in future generations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-14T16:01:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007080","title":"Genetic heritage of the Baphuthi highlights an over-ethnicised notion of 'Bushman' in the Maloti-Drakensberg, southern Africa","description":"Using contemporary people as proxies for ancient communities is a contentious but necessary practice in anthropology. In southern Africa, the distinction between the Cape KhoeSan and eastern KhoeSan remains unclear as ethnicity labels have been changed through time and most communities were decimated if not extirpated. The eastern KhoeSan may have had genetic distinctions from neighbouring communities who speak Bantu languages and KhoeSan further away, alternatively the identity may not have been tied to any notion of biology, instead denoting communities with a nomadic 'lifeway' distinct from African agro-pastoralism. The Baphuthi of the 1800s in the Maloti-Drakensberg, southern Africa had a substantial KhoeSan constituency and a lifeway of nomadism, cattle raiding, and horticulture. Baphuthi heritage could provide insights into the history of the eastern KhoeSan. We examine genetic affinities of 23 Baphuthi to discern whether the narrative of KhoeSan descent reflects distinct genetic ancestry. Genome-wide SNP data (Illumina GSA) were merged with 52 global populations, for 160K SNPs. Genetic analyses show no support for a unique eastern KhoeSan ancestry distinct from other KhoeSan or southern Bantu-speakers. The Baphuthi have strong affinities with early-arriving southern Bantu-speaking (Nguni) communities, as the later-arriving non-Nguni show strong evidence of recent African admixture possibly related to Late-Iron Age migrations. The references to communities as 'San',and 'Bushman' in historic literature has often been misconstrued as notions of ethnic/biological distinctions. The terms may have reflected ambiguous references to non-sedentary polities instead, as seems to be the case for the eastern ‘Bushman’ heritage of the Baphuthi.","abstract":"Using contemporary people as proxies for ancient communities is a contentious but necessary practice in anthropology. In southern Africa, the distinction between the Cape KhoeSan and eastern KhoeSan remains unclear as ethnicity labels have been changed through time and most communities were decimated if not extirpated. The eastern KhoeSan may have had genetic distinctions from neighbouring communities who speak Bantu languages and KhoeSan further away, alternatively the identity may not have been tied to any notion of biology, instead denoting communities with a nomadic 'lifeway' distinct from African agro-pastoralism. The Baphuthi of the 1800s in the Maloti-Drakensberg, southern Africa had a substantial KhoeSan constituency and a lifeway of nomadism, cattle raiding, and horticulture. Baphuthi heritage could provide insights into the history of the eastern KhoeSan. We examine genetic affinities of 23 Baphuthi to discern whether the narrative of KhoeSan descent reflects distinct genetic ancestry. Genome-wide SNP data (Illumina GSA) were merged with 52 global populations, for 160K SNPs. Genetic analyses show no support for a unique eastern KhoeSan ancestry distinct from other KhoeSan or southern Bantu-speakers. The Baphuthi have strong affinities with early-arriving southern Bantu-speaking (Nguni) communities, as the later-arriving non-Nguni show strong evidence of recent African admixture possibly related to Late-Iron Age migrations. The references to communities as 'San',and 'Bushman' in historic literature has often been misconstrued as notions of ethnic/biological distinctions. The terms may have reflected ambiguous references to non-sedentary polities instead, as seems to be the case for the eastern ‘Bushman’ heritage of the Baphuthi.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-14T18:26:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007081","title":"PEACE melanoma 14","description":"Understanding the evolutionary pathways to metastasis and resistance to immune checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here we present the most comprehensive intra-patient metastatic melanoma dataset assembled to date as part of the PEACE research autopsy programme, including exome, panel-sequenced, RNA-seq, and single-cell whole-genome sequencing samples from 14 ICI-treated patients. The main goals of the project are to decipher the evolutionary dynamics of melanoma metastases and to elucidate mechnisms of resistance to therapies.","abstract":"Understanding the evolutionary pathways to metastasis and resistance to immune checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here we present the most comprehensive intra-patient metastatic melanoma dataset assembled to date as part of the PEACE research autopsy programme, including exome, panel-sequenced, RNA-seq, and single-cell whole-genome sequencing samples from 14 ICI-treated patients. The main goals of the project are to decipher the evolutionary dynamics of melanoma metastases and to elucidate mechnisms of resistance to therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-15T10:58:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007082","title":"Covid19 WGS Variant analysis","description":"The Samples were collected from Saint James's Hospital, Dublin and after informed consent Extracted Genomic DNA samples were prepared and sequenced using the Automated Illumina TruSeq PCR-free methodology. The raw reads aligned with GRCh38 human genome and variant calling has been accomplished by GATK. The resulted GVCF and vcf has been submitted as variant analysis.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-15T14:48:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007083","title":"Spatial transcriptomics reveal topological immune landscapes of Asian head and neck angiosarcoma","description":"Angiosarcomas are rare malignant tumors of the endothelium, arising commonly from the head and neck region (AS-HN) and recently associated with ultraviolet (UV) exposure and human herpesvirus-7 (HHV-7) infection. We examined 81 cases of angiosarcomas, including 47 cases of AS-HN, integrating information from whole genome sequencing, gene expression profiling and spatial transcriptomics (10X Visium). In the AS-HN cohort, we observed recurrent somatic mutations in CSMD3 (18%), LRP1B (18%), MUC16 (18%), POT1 (16%) and TP53 (16%). UV-positive AS-HN harbored significantly higher tumor mutation burden (TMB) than UV-negative cases (p=0.0294). NanoString profiling identified three clusters with distinct tumor inflammation signature (TIS) scores (p&lt;0.001). Spatial transcriptomics revealed topological profiles of the tumor microenvironment, identifying dominant but tumor-excluded inflammatory signals in “immune-hot” cases and immune foci even in otherwise “cold” cases. In conclusion, spatial transcriptomics reveal the tumor immune landscape of angiosarcoma, and in combination with multi-omic information, may improve implementation of treatment strategies.","abstract":"Angiosarcomas are rare malignant tumors of the endothelium, arising commonly from the head and neck region (AS-HN) and recently associated with ultraviolet (UV) exposure and human herpesvirus-7 (HHV-7) infection. We examined 81 cases of angiosarcomas, including 47 cases of AS-HN, integrating information from whole genome sequencing, gene expression profiling and spatial transcriptomics (10X Visium). In the AS-HN cohort, we observed recurrent somatic mutations in CSMD3 (18%), LRP1B (18%), MUC16 (18%), POT1 (16%) and TP53 (16%). UV-positive AS-HN harbored significantly higher tumor mutation burden (TMB) than UV-negative cases (p=0.0294). NanoString profiling identified three clusters with distinct tumor inflammation signature (TIS) scores (p&lt;0.001). Spatial transcriptomics revealed topological profiles of the tumor microenvironment, identifying dominant but tumor-excluded inflammatory signals in “immune-hot” cases and immune foci even in otherwise “cold” cases. In conclusion, spatial transcriptomics reveal the tumor immune landscape of angiosarcoma, and in combination with multi-omic information, may improve implementation of treatment strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-16T17:21:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007084","title":"sWGS of Pap test smears from healthy donors and HGSOC patients and matched tumor tissue","description":"Shallow whole genome sequencing was performed on Pap test smears considering at least 10 M reads per sample. The cohort consists of 77 samples from healthy women, i.e. no tumor diagnosis, and 65 samples from women with a diagnosis of high-grade serous ovarian cancer (HGSOC) taken months or years before diagnosis. \n44 primary tumor samples matched to the respective HGSOC patients were sequenced in the same manner as the Pap test smears.","abstract":"Shallow whole genome sequencing was performed on Pap test smears considering at least 10 M reads per sample. The cohort consists of 77 samples from healthy women, i.e. no tumor diagnosis, and 65 samples from women with a diagnosis of high-grade serous ovarian cancer (HGSOC) taken months or years before diagnosis. \n44 primary tumor samples matched to the respective HGSOC patients were sequenced in the same manner as the Pap test smears.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-17T08:43:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007085","title":"Papua New Guinean Genome Altitude Project","description":null,"abstract":"High-coverage whole genome sequences were collected to study patterns of genomic variation across the broad geography of Papua New Guinea. This region has experienced an extremely complex demographic history, including repeated bouts of admixture with archaic and modern human groups. This dataset reports whole genome sequences for 163  individuals from different regions (Mt Wilhelm, Daru, Port Moresby). Particular attention has been paid in the original study to genomic signals that are informative for population history, and adaptive history, including admixture with archaic hominins and the role of modern human admixture during the late Pleistocene and Holocene.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-17T10:43:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007086","title":"The impact of mutational clonality in predicting the response to anti-PD-L1/PD-L1 in advanced urothelial cancer","description":"The advent of immune checkpoint inhibitors (ICI) has radically changed the management and therapeutic treatment landscape for patients with cancer. It has been shown that the use of these inhibitors can result in long-term complete remissions even in cases with advanced stages of the disease. However, only a small fraction of patients respond to the treatment. A better understanding of which factors could drive this clinical benefit is fundamental to building more accurate predictive biomarkers and developing alternative therapeutic options for patients who are unlikely to benefit.  In order to address this issue, we have generated and analyzed whole exome sequencing (WES) and RNA sequencing (RNASeq) data from a cohort of metastatic urothelial carcinoma patients (N = 27) treated with ICI such as anti-PD-(L)1 monoclonal antibodies.","abstract":"The advent of immune checkpoint inhibitors (ICI) has radically changed the management and therapeutic treatment landscape for patients with cancer. It has been shown that the use of these inhibitors can result in long-term complete remissions even in cases with advanced stages of the disease. However, only a small fraction of patients respond to the treatment. A better understanding of which factors could drive this clinical benefit is fundamental to building more accurate predictive biomarkers and developing alternative therapeutic options for patients who are unlikely to benefit.  In order to address this issue, we have generated and analyzed whole exome sequencing (WES) and RNA sequencing (RNASeq) data from a cohort of metastatic urothelial carcinoma patients (N = 27) treated with ICI such as anti-PD-(L)1 monoclonal antibodies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-17T13:28:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007087","title":"Evolutionary landscape of clonal hematopoiesis in 3359 individuals from the general population","description":"This project contains longitudinal data for processed somatic variant calls and data on core phenotypic variables for 3359 community-based individuals ≥60 years, a sub-cohort of the population-based Lifelines cohort (167,729 participants). Cases with peripheral blood count abnormalities and population-based controls were included. Next-generation sequencing data were generated with a median time period of 43 months between baseline and follow-up visit. For 327 individuals a third visit sample was included. Error-corrected sequencing was performed using single-molecule tagged molecular inversion probes targeting 27 myeloid and lymphoid driver genes. The threshold for variant calling was set at ≥1% VAF and ≥10 consensus variant reads. Details on sample selection, sequencing technique, variant calling procedures and data curation are described (van Zeventer et al. 2023).","abstract":"This project contains longitudinal data for processed somatic variant calls and data on core phenotypic variables for 3359 community-based individuals ≥60 years, a sub-cohort of the population-based Lifelines cohort (167,729 participants). Cases with peripheral blood count abnormalities and population-based controls were included. Next-generation sequencing data were generated with a median time period of 43 months between baseline and follow-up visit. For 327 individuals a third visit sample was included. Error-corrected sequencing was performed using single-molecule tagged molecular inversion probes targeting 27 myeloid and lymphoid driver genes. The threshold for variant calling was set at ≥1% VAF and ≥10 consensus variant reads. Details on sample selection, sequencing technique, variant calling procedures and data curation are described (van Zeventer et al. 2023).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-17T14:40:00+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007088","title":"Nasal Polyp RNAsequencing, Skaraborg Sweden","description":"Whole-transcriptome sequencing (RNAseq) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and controls. Differential expression patterns in genes involved in cilia, viral defense and NKT-cell specific pathways, suggesting a role of viral immunity in combination with cilia functionality in CRSwNP.","abstract":"Whole-transcriptome sequencing (RNAseq) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and controls. Differential expression patterns in genes involved in cilia, viral defense and NKT-cell specific pathways, suggesting a role of viral immunity in combination with cilia functionality in CRSwNP.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-18T09:07:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007089","title":"Quantitative analysis of a novel DNA hypermethylation panel for lung cancer diagnosis using bronchial specimens","description":"Non-diagnostic findings in Transbronchial Lung Biopsy (TBLB) and Endobronchial Ultrasound-guided Transbronchial Lung Biopsy (EBUS-TBLB) are not uncommon. A challenge is to improve lung cancer detection by TBLB/EBUS-TBLB. In order to improve the diagnostic yield of bronchoscopy, we used 850K methylation chip to identify methylation sites that distinguish malignant from benign lung nodules.We found that the combination of HOXA7, SHOX2,and SCT methylation analysis has the best diagnostic yield in 123 bronchial washing (sensitivity: 74·1%; AUC: 0·851) and 172 brushing samples (sensitivity: 86·1%; AUC: 0·915). We developed a kit comprising these three genes and validated the kit in 329 unique bronchial washing samples, 397 unique brushing samples, and 179 unique patients with both washing and brushing samples. The diagnostic accuracy of the panel alone in lung cancer diagnosis was 86·9%, 91·2% and 95% in bronchial washing, brushing, and washing+brushing samples, respectively. The panel's sensitivity in combination with cytology, rapid on-site evaluation (ROSE), and histology in lung cancer diagnosis was 90·8% and 95.8% in bronchial washing and brushing samples, respectively, and 100% in washing+brushing samples. Quantitative analysis of the three-gene panel improves lung cancer diagnosis by bronchoscopy.","abstract":"Non-diagnostic findings in Transbronchial Lung Biopsy (TBLB) and Endobronchial Ultrasound-guided Transbronchial Lung Biopsy (EBUS-TBLB) are not uncommon. A challenge is to improve lung cancer detection by TBLB/EBUS-TBLB. In order to improve the diagnostic yield of bronchoscopy, we used 850K methylation chip to identify methylation sites that distinguish malignant from benign lung nodules.We found that the combination of HOXA7, SHOX2,and SCT methylation analysis has the best diagnostic yield in 123 bronchial washing (sensitivity: 74·1%; AUC: 0·851) and 172 brushing samples (sensitivity: 86·1%; AUC: 0·915). We developed a kit comprising these three genes and validated the kit in 329 unique bronchial washing samples, 397 unique brushing samples, and 179 unique patients with both washing and brushing samples. The diagnostic accuracy of the panel alone in lung cancer diagnosis was 86·9%, 91·2% and 95% in bronchial washing, brushing, and washing+brushing samples, respectively. The panel's sensitivity in combination with cytology, rapid on-site evaluation (ROSE), and histology in lung cancer diagnosis was 90·8% and 95.8% in bronchial washing and brushing samples, respectively, and 100% in washing+brushing samples. Quantitative analysis of the three-gene panel improves lung cancer diagnosis by bronchoscopy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-18T14:54:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007090","title":"Point-of-care monitoring of head and neck cancer treatment response and recurrence development using nanopore-based ctDNA consensus sequencing","description":null,"abstract":"Levels of circulating tumor DNA (ctDNA) in liquid biopsies may serve as a sensitive biomarker for real-time, minimally-invasive tumor diagnostics and monitoring. However, detecting ctDNA is challenging, as much fewer than 5% of the cell-free DNA in the blood typically originates from the tumor. To detect lowly abundant molecules, extremely sensitive sequencing methods are required. We developed a new technique, CyclomicsSeq, which is based on Oxford Nanopore sequencing of concatenated copies of a single DNA molecule, and applied this to amplicon(s) of TP53 in patients with advanced head and neck cancer squamous cell carcinoma (HNSCC) and healthy controls.","study_type":"Forensic or Paleo-genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-19T19:05:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007091","title":"Cell-to-cell variability in Myc dynamics drives transcriptional heterogeneity in cancer cells","description":null,"abstract":"Cell-to-cell heterogeneity is vital for tumor evolution and survival. How cancer cells achieve and exploit this heterogeneity remains an active area of research. Here we identify c-Myc as a highly heterogeneously expressed transcription factor, and an orchestrator of transcriptional and phenotypic diversity in cancer cells. By monitoring endogenous c-Myc protein in individual living cells, we uncovered the surprising pulsatile nature of c-Myc expression and the extensive cell-to-cell variability in its dynamics. We further demonstrated that heterogeneity in c-Myc dynamics leads to variable target gene transcription, and that timing of c-Myc expression predicts cell-cycle progression rates and drug sensitivities. Together, our data advocates for a model in which cancer cells increase the heterogeneity of functionally diverse transcription factors such as c-Myc to rapidly survey transcriptional landscapes and survive stress.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-20T16:42:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007092","title":"Multiple Myeloma follow-up sequencing study","description":"A total of 40 Multiple Myeloma (MM) patients at clinical relapse who progressed during Proteasome Inhibitors (PIs) or Immunomodulating Drugs (IMiDs)-based therapies and who are assigned to antiCD38-based salvage treatments, will be enrolled. We will collect bone marrow (BM) and peripheral blood (PB) samples from patients at specific timepoints: baseline (BM, PB and buccal swab) every 3 month (PB) achievement of response (≥ Very Good Partial Response (VGPR)) (BM and PB) relapse or refractory status to antiCD38-based treatments (BM and PB) Samples will be processed and stored in the \"Hematological Laboratory\" located in the University of Turin (Italy) for various proposed analyses: at specific time-points CD138+ (Plasma Cells-PCs) awill be immunomagnetically enriched from the BM mononuclear cells and frozen as viable cells in dimethyl sulfoxide (DMSO); PB mononuclear cells (PBMCs) will be isolated from whole blood by density-gradient centrifugation, and frozen as above; plasma fraction from PB and BM will be obtained by centrifugation and stored frozen; Neutrophils will be obtained at the time of enrollment as a source of control germline DNA and stored frozen.","abstract":"A total of 40 Multiple Myeloma (MM) patients at clinical relapse who progressed during Proteasome Inhibitors (PIs) or Immunomodulating Drugs (IMiDs)-based therapies and who are assigned to antiCD38-based salvage treatments, will be enrolled. We will collect bone marrow (BM) and peripheral blood (PB) samples from patients at specific timepoints: baseline (BM, PB and buccal swab) every 3 month (PB) achievement of response (≥ Very Good Partial Response (VGPR)) (BM and PB) relapse or refractory status to antiCD38-based treatments (BM and PB) Samples will be processed and stored in the \"Hematological Laboratory\" located in the University of Turin (Italy) for various proposed analyses: at specific time-points CD138+ (Plasma Cells-PCs) awill be immunomagnetically enriched from the BM mononuclear cells and frozen as viable cells in dimethyl sulfoxide (DMSO); PB mononuclear cells (PBMCs) will be isolated from whole blood by density-gradient centrifugation, and frozen as above; plasma fraction from PB and BM will be obtained by centrifugation and stored frozen; Neutrophils will be obtained at the time of enrollment as a source of control germline DNA and stored frozen.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-20T17:01:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007093","title":"Long-term organoid culture of a small intestinal neuroendocrine tumor","description":"Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and highly heterogeneous neoplasms whose incidence has\nmarkedly increased over the last decades. A grading system based on the tumor cells' proliferation index predicts high-risk for G3\nNETs. However, low-to-intermediate grade (G1/G2) NETs have an unpredictable clinical course that varies from indolent to highly\nmalignant. Cultures of human cancer cells enable to perform functional perturbation analyses that are instrumental to enhance our\nunderstanding of cancer biology. To date, no tractable and reliable long-term culture of G1/G2 NET has been reported to permit\ndisease modeling and pharmacological screens. Here, we report of the first long-term culture of a G2 metastatic small intestinal\nNET that preserves the main genetic drivers of the tumor and retains expression patterns of the endocrine cell lineage.\nReplicating the tissue, this long-term culture showed a low proliferation index, and yet it could be propagated continuously\nwithout dramatic changes in the karyotype. The model was readily available for pharmacological screens using targeted agents\nand as expected, showed low tumorigenic capacity in vivo. Overall, this is the first long-term culture of NETs to faithfully\nrecapitulate many aspects of the original neuroendocrine tumor.","abstract":"Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and highly heterogeneous neoplasms whose incidence has\nmarkedly increased over the last decades. A grading system based on the tumor cells' proliferation index predicts high-risk for G3\nNETs. However, low-to-intermediate grade (G1/G2) NETs have an unpredictable clinical course that varies from indolent to highly\nmalignant. Cultures of human cancer cells enable to perform functional perturbation analyses that are instrumental to enhance our\nunderstanding of cancer biology. To date, no tractable and reliable long-term culture of G1/G2 NET has been reported to permit\ndisease modeling and pharmacological screens. Here, we report of the first long-term culture of a G2 metastatic small intestinal\nNET that preserves the main genetic drivers of the tumor and retains expression patterns of the endocrine cell lineage.\nReplicating the tissue, this long-term culture showed a low proliferation index, and yet it could be propagated continuously\nwithout dramatic changes in the karyotype. The model was readily available for pharmacological screens using targeted agents\nand as expected, showed low tumorigenic capacity in vivo. Overall, this is the first long-term culture of NETs to faithfully\nrecapitulate many aspects of the original neuroendocrine tumor.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-21T09:11:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007094","title":"Epigenetic landscape of mixed phenotype leukemias","description":"Leukemias with ambiguous lineage comprise a number of loosely defined entities, often without a clear mechanistic basis. Here, we investigated a group of such leukemias with a CpG Island Methylator Phenotype (CIMP), previously identified as CEBPA-silenced AML. Transcriptomics and epigenomics analyses revealed a hybrid myeloid/lymphoid epigenetic landscape, whereas genetic alterations were heterogenous. This suggests that CIMP leukemias are defined by their shared epigenetic profile rather than a common genetic lesion. Gene expression enrichment showed strong similarity with ETP-ALL and an early lymphoid progenitor cell of origin. Accordingly, integration of differential methylation and expression revealed widespread silencing of myeloid transcription factors (TFs), among which CEBPA was key for differentiation arrest. Hypermethylation also resulted in loss of CTCF binding, accompanied by a few changes in chromatin interactions involving critical TFs like KLF4. In conclusion, epigenetic dysregulation, and not genetic lesions, explain the mixed phenotype of a group of CIMP leukemias resembling ETP-ALL.","abstract":"Leukemias with ambiguous lineage comprise a number of loosely defined entities, often without a clear mechanistic basis. Here, we investigated a group of such leukemias with a CpG Island Methylator Phenotype (CIMP), previously identified as CEBPA-silenced AML. Transcriptomics and epigenomics analyses revealed a hybrid myeloid/lymphoid epigenetic landscape, whereas genetic alterations were heterogenous. This suggests that CIMP leukemias are defined by their shared epigenetic profile rather than a common genetic lesion. Gene expression enrichment showed strong similarity with ETP-ALL and an early lymphoid progenitor cell of origin. Accordingly, integration of differential methylation and expression revealed widespread silencing of myeloid transcription factors (TFs), among which CEBPA was key for differentiation arrest. Hypermethylation also resulted in loss of CTCF binding, accompanied by a few changes in chromatin interactions involving critical TFs like KLF4. In conclusion, epigenetic dysregulation, and not genetic lesions, explain the mixed phenotype of a group of CIMP leukemias resembling ETP-ALL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-21T10:08:16+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007095","title":"BMP4 and temozolomide synergize in the majority of patient derived glioblastoma cultures","description":"The poor prognosis of patients with glioblastoma is partly due to resistance to standard treatment, which combines chemoradiation using temozolomide (TMZ). The concept of cancer stem cells provided new insight into tumor resistance and management, and isolated Glioblastoma stem-like cells (GSCs) which contribute to this therapy resistance. Bone morphogenetic protein 4 (BMP4) is a differentiation factor that stimulates astroglial differentiation of such GSCs, thereby reducing their self-renewal. Exposing GSCs to BMP4 could therefore sensitize them to chemotherapy with TMZ, but previous studies with various treatment paradigms have produced contradictory results in this matter. Therefore, we re-defined the optimal treatment paradigm for the combination of TMZ and BMP4 and subsequently re-assessed the inter-tumoral variability in response to co-treatment with TMZ+BMP4 in vitro. First, the simultaneous treatment was found more effective than sequential therapy. Second, after application of our optimized treatment protocol, 70% of a total of 20 patient-derived glioblastoma cultures showed synergy when the treatments were combined. The synergistic effect was a result of increased cellular apoptosis and not of decreased proliferation. Comparative RNA-sequencing suggested that combination treatment results in decreased MAPK signaling. We conclude that addition of BMP4 to standard therapy with TMZ could enlarge the group of patients with good therapeutic response.","abstract":"The poor prognosis of patients with glioblastoma is partly due to resistance to standard treatment, which combines chemoradiation using temozolomide (TMZ). The concept of cancer stem cells provided new insight into tumor resistance and management, and isolated Glioblastoma stem-like cells (GSCs) which contribute to this therapy resistance. Bone morphogenetic protein 4 (BMP4) is a differentiation factor that stimulates astroglial differentiation of such GSCs, thereby reducing their self-renewal. Exposing GSCs to BMP4 could therefore sensitize them to chemotherapy with TMZ, but previous studies with various treatment paradigms have produced contradictory results in this matter. Therefore, we re-defined the optimal treatment paradigm for the combination of TMZ and BMP4 and subsequently re-assessed the inter-tumoral variability in response to co-treatment with TMZ+BMP4 in vitro. First, the simultaneous treatment was found more effective than sequential therapy. Second, after application of our optimized treatment protocol, 70% of a total of 20 patient-derived glioblastoma cultures showed synergy when the treatments were combined. The synergistic effect was a result of increased cellular apoptosis and not of decreased proliferation. Comparative RNA-sequencing suggested that combination treatment results in decreased MAPK signaling. We conclude that addition of BMP4 to standard therapy with TMZ could enlarge the group of patients with good therapeutic response.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-21T10:33:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007096","title":"Comprehensive Copy Number Aberration analysis by digital Multiplex Ligation-dependent Probe Amplification in pediatric acute lymphoblastic leukemia","description":null,"abstract":"In this study a next-generation sequencing based method was applied to comprehensively screen for recurrent, disease-relevant copy number aberrations in a cohort of Hungarian patients. Diagnostic bone marrow samples from 260 children with B-cell acute lymphoblastic leukemia and were investigated by digital multiplex ligation-dependent probe amplification using the disease-specific D007 probemix. Whole chromosome gains and losses, as well as subchromosomal copy number aberrations were simultaneously profiled.","study_type":"Cancer Genomics","pubmed_ids":[31857684],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007097","title":"Gene expression profiles in paediatric ETV6-RUNX1 leukemia","description":null,"abstract":"ETV6-RUNX1 (E::R) subgroup is the second most frequent form of B cell acute lymphoblastic leukemia (B-ALL) in childhood. This subgroup of ALL generally presents with low-risk features and responds well to chemotherapy with ensuing favorable prognosis. Some patients, however, have a slow response to induction treatment and carry increased risk for relapse. The aim of this study is to identify differences in gene expression between E::R cases stratified by MRD (NOPHO ALL2008 protocol), and to identify potential mediators of poor therapy response.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-21T12:54:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007098","title":"JAK/STAT signaling promotes the emergence of regenerative cell states in ulcerative colitis","description":null,"abstract":"The intestinal epithelium forms a barrier to the lumen and ensures uptake of vital nutrients. During inflammatory diseases, such as ulcerative colitis (UC), this barrier is compromised. Here, we perform single-cell RNA sequencing (scRNA-seq) of epithelial cells and outline patterns of cell fate decisions in healthy individuals and patients with UC. We demonstrate that lineage biased progenitors are major sources of normal tissue replenishment, and that patterns of cell behavior are profoundly altered in UC. We furthermore identify unique regenerative cell states linked to JAK/STAT activation extending into the non-inflamed areas of the colon. In organoid models, this can be mimicked by cytokine mediated activation of JAK/STAT leading to the emergence of cell populations with regenerative potential. These findings have profound implications for our understanding of tissue regeneration and illustrates how cytokine signaling influences cell fate decisions. This suggests widespread consequences in patients with chronic ulcerative conditions.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-21T13:49:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007099","title":"Implementation of pediatric precision oncology into clinical practice: The individualized Therapies for Children with cancer program “iTHER”","description":"iTHER is a prospective national precision oncology program aiming to define tumor molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory pediatric tumors in order to identify relevant aberrations to inform treatment.\nFrom April 2017 to April 2021, 302 samples of 253 patients were included.  Comprehensive molecular profiling utilizing lcWGS, WES, RNAseq, Affymetrix, and/or 850k methylation profiling was performed for 226 samples. Germline pathogenic variants were identified in 16% of patients. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with priority levels very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%). Diagnosis was revised or refined in 8 patients (3.5%). Spatial and temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analysis.\nOf 137 patients with follow-up beyond 12 months, 21 molecularly matched treatments were applied in 19 patients (13.9%) with modest response. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial.\niTHER demonstrates feasibility of comprehensive molecular profiling across all ages, tumor types and stages in pediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants within a clinically relevant timeframe. Therefore, WES and RNAseq is implemented into standard clinical care at the Princess Máxima Center for all children. Improved access to targeted treatments within biology-driven combination trials is required to eventually improve survival.","abstract":"iTHER is a prospective national precision oncology program aiming to define tumor molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory pediatric tumors in order to identify relevant aberrations to inform treatment.\nFrom April 2017 to April 2021, 302 samples of 253 patients were included.  Comprehensive molecular profiling utilizing lcWGS, WES, RNAseq, Affymetrix, and/or 850k methylation profiling was performed for 226 samples. Germline pathogenic variants were identified in 16% of patients. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with priority levels very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%). Diagnosis was revised or refined in 8 patients (3.5%). Spatial and temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analysis.\nOf 137 patients with follow-up beyond 12 months, 21 molecularly matched treatments were applied in 19 patients (13.9%) with modest response. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial.\niTHER demonstrates feasibility of comprehensive molecular profiling across all ages, tumor types and stages in pediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants within a clinically relevant timeframe. Therefore, WES and RNAseq is implemented into standard clinical care at the Princess Máxima Center for all children. Improved access to targeted treatments within biology-driven combination trials is required to eventually improve survival.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-21T14:42:13+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007100","title":"The genomic landscape of squamous cell carcinoma of the head and neck with lymphatic metastasis","description":null,"abstract":"Using whole exome sequencing, we characterized samples of matched primary tumor (PT) and lymph node metastatic (LNM) tissues from 104 HNSCC patients for which comprehensive clinical data with the median follow up of 4 years is available. This cohort displays substantial intra-patient heterogeneity: matched PTs and LNMs share on average 44% of mutations but mutations in HNSCC cancer genes are typically present in both PTs and matched LNMs. The evolutionary timing of driver alterations differed between HPV-positive and HPV-negative HNSCC.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007101","title":"Cancer sequencing for somatic variant calling","description":"This dataset includes WES and RNAseq for 11 patients with metastatic melanoma, lung, kidney, and stomach cancers, enrolled in phase I clinical trials of TIL ACT (NCT03475134 &amp; NCT04643574). WES was performed on matched cancer and healthy tissues, whereas RNAseq was performed on cancer tissues, using Illumina HiSeq 2500/4000 and Illumina NextSeq 550 systems.","abstract":"This dataset includes WES and RNAseq for 11 patients with metastatic melanoma, lung, kidney, and stomach cancers, enrolled in phase I clinical trials of TIL ACT (NCT03475134 &amp; NCT04643574). WES was performed on matched cancer and healthy tissues, whereas RNAseq was performed on cancer tissues, using Illumina HiSeq 2500/4000 and Illumina NextSeq 550 systems.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-22T11:51:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007102","title":"Meckel_Cambridge_Behjati_WellcomeCore_DNA_Managed_Access","description":"We will compare normal bowel with bowel effected by Meckels.","abstract":"We will compare normal bowel with bowel effected by Meckels.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007103","title":"Genomic profiling of Rare Tumors","description":"Utilizing the rare and unique patient samples provided by Pattern Medicine, LLC, MD Anderson will molecularly characterize rare cancer samples, and potentially generate a collection of preclinical models to enable identification of novel therapeutic targets and concepts, as well as evaluation of innovative treatment strategies.","abstract":"Utilizing the rare and unique patient samples provided by Pattern Medicine, LLC, MD Anderson will molecularly characterize rare cancer samples, and potentially generate a collection of preclinical models to enable identification of novel therapeutic targets and concepts, as well as evaluation of innovative treatment strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-22T13:46:33+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007104","title":"Whole Exome Sequencing data of six chRCC tumors corresponding to three patients","description":"Mammalian target of rapamycin (mTOR) is a central regulator of mammalian metabolism and physiology. Aberrant hyperactivation of the mTOR pathway promotes tumor growth and metastasis, and can also promote tumor resistance to chemotherapy and cancer drugs; this makes mTOR an attractive cancer therapeutic target. mTOR inhibitors have been approved to treat cancer; however, the mechanisms underlying drug sensitivity remain poorly understood. Here, whole exome sequencing of three chromophobe renal cell carcinoma (chRCC) patients with exceptional mTOR inhibitor sensitivity revealed that all three patients shared somatic mutations in the deubiquitinase USP9X. The clonal characteristics of the mutations, which were amassed by studying multiple patients’ primary and metastatic samples from various years, together with the low USP9X mutation rate in unselected chRCC series, reinforced a causal link between USP9X and mTOR inhibitor sensitivity. Rapamycin treatment of USP9X-depleted HeLa and renal cancer 786-O cells, along with the pharmacological inhibition of USP9X, confirmed that this protein plays a role in patients’ sensitivity to mTOR inhibition. USP9X was not found to exert a direct effect on mTORC1, but subsequent ubiquitylome analyses identified p62 as a direct USP9X target. Increased p62 ubiquitination and the augmented rapamycin effect upon bortezomib treatment, together with the results of p62 and LC3 immunofluorescence assays, suggested that dysregulated autophagy in USP9X-depleted cells can have a synergistic effect with mTOR inhibitors. In summary, we show that USP9X constitutes a potential novel marker of sensitivity to mTOR inhibitors in chRCC patients, and represents a clinical strategy for increasing the sensitivity to these drugs.","abstract":"Mammalian target of rapamycin (mTOR) is a central regulator of mammalian metabolism and physiology. Aberrant hyperactivation of the mTOR pathway promotes tumor growth and metastasis, and can also promote tumor resistance to chemotherapy and cancer drugs; this makes mTOR an attractive cancer therapeutic target. mTOR inhibitors have been approved to treat cancer; however, the mechanisms underlying drug sensitivity remain poorly understood. Here, whole exome sequencing of three chromophobe renal cell carcinoma (chRCC) patients with exceptional mTOR inhibitor sensitivity revealed that all three patients shared somatic mutations in the deubiquitinase USP9X. The clonal characteristics of the mutations, which were amassed by studying multiple patients’ primary and metastatic samples from various years, together with the low USP9X mutation rate in unselected chRCC series, reinforced a causal link between USP9X and mTOR inhibitor sensitivity. Rapamycin treatment of USP9X-depleted HeLa and renal cancer 786-O cells, along with the pharmacological inhibition of USP9X, confirmed that this protein plays a role in patients’ sensitivity to mTOR inhibition. USP9X was not found to exert a direct effect on mTORC1, but subsequent ubiquitylome analyses identified p62 as a direct USP9X target. Increased p62 ubiquitination and the augmented rapamycin effect upon bortezomib treatment, together with the results of p62 and LC3 immunofluorescence assays, suggested that dysregulated autophagy in USP9X-depleted cells can have a synergistic effect with mTOR inhibitors. In summary, we show that USP9X constitutes a potential novel marker of sensitivity to mTOR inhibitors in chRCC patients, and represents a clinical strategy for increasing the sensitivity to these drugs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-22T15:16:04+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007105","title":"Genomic Landscape of Follicular Lymphoma Across a Wide Spectrum of Clinical Behaviors","description":null,"abstract":"Dataset accompanying the study entitled \"Genomic Landscape of Follicular Lymphoma Across a Wide Spectrum of Clinical Behaviors\", which includes data from a next generation sequencing panel capturing 121 genes recurrently altered in B-cell lymphomas in 55 diagnostic and 10 relapse follicular lymphoma samples selected based on their need of treament and timing of relapse.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-22T16:41:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007106","title":"Covid19 WGS Raw Read files","description":"The Samples were collected from Saint James's Hospital, Dublin and after informed consent Extracted Genomic DNA samples were prepared and sequenced using the Automated Illumina TruSeq PCR-free methodology.","abstract":"The Samples were collected from Saint James's Hospital, Dublin and after informed consent Extracted Genomic DNA samples were prepared and sequenced using the Automated Illumina TruSeq PCR-free methodology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-22T17:59:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007107","title":"TIGIT is the central player in T-cell suppression associated with CAR T-cell relapse in mantle cell lymphoma","description":null,"abstract":"Background\nChimeric antigen receptor (CAR) T-cell therapy using brexucabtagene autoleucel (BA) induces remission in many patients with mantle cell lymphoma (MCL), and BA is the only CAR T-cell therapy approved by the FDA for MCL. However, development of relapses to BA is recognized with poor patient outcomes. Multiple CAR T-cell therapies have been approved for other lymphomas and the resistance mechanisms have been investigated. However, the mechanisms underlying BA relapse in MCL have not been investigated and whether any previously reported resistance mechanisms apply to BA-relapsed patients with MCL is unknown.\n\nMethods\nTo interrogate BA resistance mechanisms in MCL, we performed single-cell RNA sequencing on 39 longitudinally collected samples from 15 BA-treated patients, and multiplex cytokine profiling on 80 serial samples from 20 patients.\n\nResults\nWe demonstrate that after BA relapse, the proportion of T cells, especially cytotoxic T cells (CTLs), decreased among non-tumor cells, while the proportion of myeloid cells correspondingly increased. TIGIT, LAG3, and CD96 were the predominant checkpoint molecules expressed on exhausted T cells and CTLs; only TIGIT was significantly increased after relapse. CTLs expanded during remission, and then contracted during relapse with upregulated TIGIT expression. Tumor cells also acquired TIGIT expression after relapse, leading to the enhanced interaction of tumor cell TIGIT with monocyte CD155/PVR. In myeloid cells, post-relapse HLA-II expression was reduced relative to pretreatment and during remission. Myeloid-derived suppressor cells (MDSCs) were enriched after relapse with elevated expression of activation markers, including CLU (clusterin) and VCAN (versican). Extracellular chemokines (CCL4, CXCL9, CXCL13), soluble checkpoint inhibitors (sPD-L1, sTIM3, s4-1BB), and soluble receptors (sIL-2R, sTNFRII) were decreased during remission but elevated after relapse.\n\nConclusions\nOur data demonstrate that multiple tumor-intrinsic and -extrinsic factors are associated with T-cell suppression and BA relapse. Among these, TIGIT appears to be the central player given its elevated expression after BA relapse in not only CTLs but also MCL cells. The acquisition of TIGIT expression on tumor cells is MCL-specific and has not been reported in other CAR T-treated diseases. Together, our data suggest that co-targeting TIGIT may prevent CAR T relapses and thus promote long-term progression-free survival in MCL patients.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007108","title":"Long-term organoid culture of a small intestinal neuroendocrine tumor rna-seq","description":"Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and highly heterogeneous neoplasms whose incidence has\nmarkedly increased over the last decades. A grading system based on the tumor cells' proliferation index predicts high-risk for G3\nNETs. However, low-to-intermediate grade (G1/G2) NETs have an unpredictable clinical course that varies from indolent to highly\nmalignant. Cultures of human cancer cells enable to perform functional perturbation analyses that are instrumental to enhance our\nunderstanding of cancer biology. To date, no tractable and reliable long-term culture of G1/G2 NET has been reported to permit\ndisease modeling and pharmacological screens. Here, we report of the first long-term culture of a G2 metastatic small intestinal\nNET that preserves the main genetic drivers of the tumor and retains expression patterns of the endocrine cell lineage.\nReplicating the tissue, this long-term culture showed a low proliferation index, and yet it could be propagated continuously\nwithout dramatic changes in the karyotype. The model was readily available for pharmacological screens using targeted agents\nand as expected, showed low tumorigenic capacity in vivo. Overall, this is the first long-term culture of NETs to faithfully\nrecapitulate many aspects of the original neuroendocrine tumor.","abstract":"Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and highly heterogeneous neoplasms whose incidence has\nmarkedly increased over the last decades. A grading system based on the tumor cells' proliferation index predicts high-risk for G3\nNETs. However, low-to-intermediate grade (G1/G2) NETs have an unpredictable clinical course that varies from indolent to highly\nmalignant. Cultures of human cancer cells enable to perform functional perturbation analyses that are instrumental to enhance our\nunderstanding of cancer biology. To date, no tractable and reliable long-term culture of G1/G2 NET has been reported to permit\ndisease modeling and pharmacological screens. Here, we report of the first long-term culture of a G2 metastatic small intestinal\nNET that preserves the main genetic drivers of the tumor and retains expression patterns of the endocrine cell lineage.\nReplicating the tissue, this long-term culture showed a low proliferation index, and yet it could be propagated continuously\nwithout dramatic changes in the karyotype. The model was readily available for pharmacological screens using targeted agents\nand as expected, showed low tumorigenic capacity in vivo. Overall, this is the first long-term culture of NETs to faithfully\nrecapitulate many aspects of the original neuroendocrine tumor.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-23T08:46:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007109","title":"Oesophageal_Adenocarcinoma_Organoid_ONT","description":"Oxford Nanopore Sequencing of 5 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical resection of the tumour. All model derivations took place with the CGaP facility in Sanger. This Oxford Nanopore data will be combined with other sequencing data in order to generate accurate reference cancer genomes.","abstract":"There is complex interplay between underlying genetic sequence and epigenetic factors, however this interplay is still illusive. Massively reconstructed cancer genomes can be used in order to better understand this relationship. Five oesophageal adenocarcinoma organoids will be sequenced using long read sequencing technologies and will be profiled for a range of epigenetic marks. Combination of genetic and epigenetic data will allow the thorough characterisation of reference cancer genomes and will provide novel insights into mechanisms of gene regulation.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007110","title":"Single-cell and bulk RNA-sequencing of nivolumab-treated glioblastoma","description":"Glioblastoma is a highly aggressive type of brain tumour for which there is no curative treatment available. Immunotherapies have shown limited responses in unselected glioblastoma patients, and it is currently not well understood what separates the few responders from the non-responders at the cellular and molecular level. Here we investigate the phenotypic and transcriptional evolutionary dynamics at single-cell resolution during nivolumab immune checkpoint treatment of eight glioblastoma patients enrolled in a translational phase I/II clinical trial.","abstract":"Glioblastoma is a highly aggressive type of brain tumour for which there is no curative treatment available. Immunotherapies have shown limited responses in unselected glioblastoma patients, and it is currently not well understood what separates the few responders from the non-responders at the cellular and molecular level. Here we investigate the phenotypic and transcriptional evolutionary dynamics at single-cell resolution during nivolumab immune checkpoint treatment of eight glioblastoma patients enrolled in a translational phase I/II clinical trial.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-23T11:41:46+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007111","title":"Genetic Determinants of Transcriptional Variation in Primary Human Monocytes Across Multiple Contexts","description":"Monocytes undergo global gene expression changes upon stimulation, thus a significant proportion of eQTL are specific to activation state. Here we systematically explore determinants of gene and transcript expression in monocytes from 185 individuals in the untreated state and post-exposure to IFNγ or lipopolysaccharide (LPS).","abstract":"Monocytes undergo global gene expression changes upon stimulation, thus a significant proportion of eQTL are specific to activation state. Here we systematically explore determinants of gene and transcript expression in monocytes from 185 individuals in the untreated state and post-exposure to IFNγ or lipopolysaccharide (LPS).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-23T11:45:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007112","title":"RNA stability controlled by m6A methylation contributes to X-to-autosome dosage compensation in mammals","description":"In mammals, X-chromosomal genes are expressed from a single copy since males (XY) possess a single X chromosome, while females (XX) undergo X inactivation. To compensate for this reduction in dosage compared to two active copies of autosomes, it has been proposed that genes from the active X chromosome exhibit dosage compensation. However, the existence and mechanism of X-to-autosome dosage compensation are still under debate. Here, we show that X-chromosomal transcripts are reduced in m6A modifications and more stable compared to their autosomal counterparts. Acute depletion of m6A selectively stabilises autosomal transcripts, resulting in perturbed dosage compensation in mouse embryonic stem cells. We propose that higher stability of X-chromosomal transcripts is directed by lower levels of m6A, indicating that mammalian dosage compensation is partly regulated by epitranscriptomic RNA modifications.","abstract":"In mammals, X-chromosomal genes are expressed from a single copy since males (XY) possess a single X chromosome, while females (XX) undergo X inactivation. To compensate for this reduction in dosage compared to two active copies of autosomes, it has been proposed that genes from the active X chromosome exhibit dosage compensation. However, the existence and mechanism of X-to-autosome dosage compensation are still under debate. Here, we show that X-chromosomal transcripts are reduced in m6A modifications and more stable compared to their autosomal counterparts. Acute depletion of m6A selectively stabilises autosomal transcripts, resulting in perturbed dosage compensation in mouse embryonic stem cells. We propose that higher stability of X-chromosomal transcripts is directed by lower levels of m6A, indicating that mammalian dosage compensation is partly regulated by epitranscriptomic RNA modifications.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-23T12:49:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007113","title":"TIGIT is the central player in T-cell suppression associated with CAR T-cell relapse in mantle cell lymphoma","description":null,"abstract":"Background\nChimeric antigen receptor (CAR) T-cell therapy using brexucabtagene autoleucel (BA) induces remission in many patients with mantle cell lymphoma (MCL), and BA is the only CAR T-cell therapy approved by the FDA for MCL. However, development of relapses to BA is recognized with poor patient outcomes. Multiple CAR T-cell therapies have been approved for other lymphomas and the resistance mechanisms have been investigated. However, the mechanisms underlying BA relapse in MCL have not been investigated and whether any previously reported resistance mechanisms apply to BA-relapsed patients with MCL is unknown.\nMethods\nTo interrogate BA resistance mechanisms in MCL, we performed single-cell RNA sequencing on 39 longitudinally collected samples from 15 BA-treated patients, and multiplex cytokine profiling on 80 serial samples from 20 patients.\nResults\nWe demonstrate that after BA relapse, the proportion of T cells, especially cytotoxic T cells (CTLs), decreased among non-tumor cells, while the proportion of myeloid cells correspondingly increased. TIGIT, LAG3, and CD96 were the predominant checkpoint molecules expressed on exhausted T cells and CTLs; only TIGIT was significantly increased after relapse. CTLs expanded during remission, and then contracted during relapse with upregulated TIGIT expression. Tumor cells also acquired TIGIT expression after relapse, leading to the enhanced interaction of tumor cell TIGIT with monocyte CD155/PVR. In myeloid cells, post-relapse HLA-II expression was reduced relative to pretreatment and during remission. Myeloid-derived suppressor cells (MDSCs) were enriched after relapse with elevated expression of activation markers, including CLU (clusterin) and VCAN (versican). Extracellular chemokines (CCL4, CXCL9, CXCL13), soluble checkpoint inhibitors (sPD-L1, sTIM3, s4-1BB), and soluble receptors (sIL-2R, sTNFRII) were decreased during remission but elevated after relapse.\nConclusions\nOur data demonstrate that multiple tumor-intrinsic and -extrinsic factors are associated with T-cell suppression and BA relapse. Among these, TIGIT appears to be the central player given its elevated expression after BA relapse in not only CTLs but also MCL cells. The acquisition of TIGIT expression on tumor cells is MCL-specific and has not been reported in other CAR T-treated diseases. Together, our data suggest that co-targeting TIGIT may prevent CAR T relapses and thus promote long-term progression-free survival in MCL patients.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-23T14:25:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007114","title":"WES_sequencing___Zambia","description":"We wish to sequence normal oesophageal epithelium and tumours from Zambian cancer patients to try and understand any differences in the mutational landscape in this country which has been shown to have a high incidence of oesophageal SCC.","abstract":"We wish to sequence normal oesophageal epithelium and tumours from Zambian cancer patients to try and understand any differences in the mutational landscape in this country which has been shown to have a high incidence of oesophageal SCC.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007115","title":"Effects of 2DG, Galactose, or Oligomycin on the epigenome remodeling induce by T cells activation.","description":"T cell activation is known to require a metabolic shift towards glycolysis, triggered by TCR-engagement . To substantiate the role of glycolysis in transcriptional reprogramming during antigen-driven T cell activation, we utilized a well-established ex-vivo model to recapitulate the process of antigen stimulation without the requirement for additional antigen-presenting cells . We initially explored and validated the conditions for both metabolic and epigenetic reprogramming. Antigen-mediated CD4+ T cells activation initiates context-specific gene-expression programs that drive effector functions and cell fates through changes in the epigenetic landscape . To evaluate global changes in histone modifications, we isolated CD4+ T cells from peripheral blood (PB) of healthy control (HC) human donors and either maintained them in resting conditions or stimulated with anti-CD3/CD28 for 24h. Rapid changes in the CD4+ epigenome and transcriptome were observed within 24h as measured by RNA-sequencing (RNA-seq) and H3K27ac chromatin immunoprecipitation followed by DNA-sequencing (ChIP-seq).To explore the requirement for metabolic reprogramming in regulating transcriptional responses after initial TCR engagement, CD4+ T cells from PB of healthy donors were isolated and activated in either the presence or absence of oligomycin (inhibitor of ATP synthase blocking the production of ATP by OXPHOS), 2-deoxyglucose (2DG; competitively inhibiting production of glucose-6-phosphate from glucose), or replacement of glucose with galactose. Galactose is metabolized through glycolysis, utilizing the Leloir pathway which is energy neutral, forcing cells to use all the pyruvate production to sustain the TCA cycle for OXPHOS and ATP synthesis at the expense of lactate production. Employing ChIP-seq and RNA-seq, inhibition of OXPHOS-mediated ATP production by oligomycin had only a limited effect on H3K27-acetylation or activation-induced transcription during the first 24h of activation. In contrast, inhibition of glycolysis by 2DG treatment compromised both H3K27-acetylation and transcriptional changes. However, under conditions of galactose-metabolism where lactate production is abrogated, activated CD4+ T cells were still able to globally remodel H3K27 acetylation and reprogram the transcriptome.","abstract":"T cell activation is known to require a metabolic shift towards glycolysis, triggered by TCR-engagement . To substantiate the role of glycolysis in transcriptional reprogramming during antigen-driven T cell activation, we utilized a well-established ex-vivo model to recapitulate the process of antigen stimulation without the requirement for additional antigen-presenting cells . We initially explored and validated the conditions for both metabolic and epigenetic reprogramming. Antigen-mediated CD4+ T cells activation initiates context-specific gene-expression programs that drive effector functions and cell fates through changes in the epigenetic landscape . To evaluate global changes in histone modifications, we isolated CD4+ T cells from peripheral blood (PB) of healthy control (HC) human donors and either maintained them in resting conditions or stimulated with anti-CD3/CD28 for 24h. Rapid changes in the CD4+ epigenome and transcriptome were observed within 24h as measured by RNA-sequencing (RNA-seq) and H3K27ac chromatin immunoprecipitation followed by DNA-sequencing (ChIP-seq).To explore the requirement for metabolic reprogramming in regulating transcriptional responses after initial TCR engagement, CD4+ T cells from PB of healthy donors were isolated and activated in either the presence or absence of oligomycin (inhibitor of ATP synthase blocking the production of ATP by OXPHOS), 2-deoxyglucose (2DG; competitively inhibiting production of glucose-6-phosphate from glucose), or replacement of glucose with galactose. Galactose is metabolized through glycolysis, utilizing the Leloir pathway which is energy neutral, forcing cells to use all the pyruvate production to sustain the TCA cycle for OXPHOS and ATP synthesis at the expense of lactate production. Employing ChIP-seq and RNA-seq, inhibition of OXPHOS-mediated ATP production by oligomycin had only a limited effect on H3K27-acetylation or activation-induced transcription during the first 24h of activation. In contrast, inhibition of glycolysis by 2DG treatment compromised both H3K27-acetylation and transcriptional changes. However, under conditions of galactose-metabolism where lactate production is abrogated, activated CD4+ T cells were still able to globally remodel H3K27 acetylation and reprogram the transcriptome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-27T09:38:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007116","title":"Covid19 Transcriptomic Data analysis in Irish Population","description":"The Samples were collected from Saint James's Hospital, Dublin and after informed consent. RNA-Sequencing library preparation was performed using the Illumina TruSeq Stranded Total RNA Library Prep Globin kit (20020612) with an input amount of 100 – 1000 ng. Library preparation was automated and processed using a Hamilton NGS Star. Library quality was assessed using the Roche KAPA Library Quantification Kit (7960298001) and GX Caliper HS Assay (CLS760672, 760517), run on Roche Lightcycler 480 II and Perkin Elmer LabChip GX Touch analyser respectively. Libraries were pooled and sequenced (75bp PE) on an Illumina NovaSeq 6000 instrument using NovaSeq 6000 S2 Reagent Kit v1.5 (20028314) targeting 50M paired reads. Raw data (BCL format) were demultiplexed and converted to FASTQ format using BCL2FastQ (Illumina). Adapters were trimmed using Skewer (PMID: 24925680) and QC assessed using FASTQC. STAR (PMID: 23104886) was used to align reads to the reference genome (GRCh38/hg38) as well as to the transcriptome (GENCODE v. 25). Quality of the RNA alignment was assessed using Picard QC. Gene and isoform quantification was performed using RSEM (PMID: 21816040). The study shares expression data (gene.results) and chimeric.junction.out.","abstract":"The Samples were collected from Saint James's Hospital, Dublin and after informed consent. RNA-Sequencing library preparation was performed using the Illumina TruSeq Stranded Total RNA Library Prep Globin kit (20020612) with an input amount of 100 – 1000 ng. Library preparation was automated and processed using a Hamilton NGS Star. Library quality was assessed using the Roche KAPA Library Quantification Kit (7960298001) and GX Caliper HS Assay (CLS760672, 760517), run on Roche Lightcycler 480 II and Perkin Elmer LabChip GX Touch analyser respectively. Libraries were pooled and sequenced (75bp PE) on an Illumina NovaSeq 6000 instrument using NovaSeq 6000 S2 Reagent Kit v1.5 (20028314) targeting 50M paired reads. Raw data (BCL format) were demultiplexed and converted to FASTQ format using BCL2FastQ (Illumina). Adapters were trimmed using Skewer (PMID: 24925680) and QC assessed using FASTQC. STAR (PMID: 23104886) was used to align reads to the reference genome (GRCh38/hg38) as well as to the transcriptome (GENCODE v. 25). Quality of the RNA alignment was assessed using Picard QC. Gene and isoform quantification was performed using RSEM (PMID: 21816040). The study shares expression data (gene.results) and chimeric.junction.out.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-27T11:59:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007117","title":"Identification of Long Non-coding RNA Biomarker of Human Lupus Nephritis Disease Activity","description":"Total RNA sequencing was performed on whole blood samples from 74 Lupus nephritis (LN) patients and 20 healthy controls. Differential expression analysis and weighted gene co-expression network analysis were performed to characterise expression changes of long non-coding RNAs (lncRNAs) in LN and identify lncRNAs with a key role in disease activity that could be used as potential blood-based biomarkers.","abstract":"Total RNA sequencing was performed on whole blood samples from 74 Lupus nephritis (LN) patients and 20 healthy controls. Differential expression analysis and weighted gene co-expression network analysis were performed to characterise expression changes of long non-coding RNAs (lncRNAs) in LN and identify lncRNAs with a key role in disease activity that could be used as potential blood-based biomarkers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-27T14:18:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007118","title":"Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes","description":"DNA methylation variations are prevalent in human obesity but evidence of a causative role in disease pathogenesis is limited. Here, we combine epigenome-wide association and integrative genomics to investigate the impact of adipocyte DNA methylation variations in human obesity. We discover extensive DNA methylation changes that are robustly associated with obesity (N=190 samples, 691 loci in subcutaneous and 173 loci in visceral adipocytes, P&lt;1x10-7). We connect obesity-associated methylation variations to transcriptomic changes at &gt;500 target genes, and identify putative methylation-transcription factor interactions. Through Mendelian Randomisation, we infer causal effects of methylation on obesity and obesity-induced metabolic disturbances at 59 independent loci. Targeted methylation sequencing, CRISPR-activation and gene silencing in adipocytes, further identifies regional methylation variations, underlying regulatory elements and novel cellular metabolic effects. Our results indicate DNA methylation is an important determinant of human obesity and its metabolic complications, and reveal mechanisms through which altered methylation may impact adipocyte functions.","abstract":"DNA methylation variations are prevalent in human obesity but evidence of a causative role in disease pathogenesis is limited. Here, we combine epigenome-wide association and integrative genomics to investigate the impact of adipocyte DNA methylation variations in human obesity. We discover extensive DNA methylation changes that are robustly associated with obesity (N=190 samples, 691 loci in subcutaneous and 173 loci in visceral adipocytes, P&lt;1x10-7). We connect obesity-associated methylation variations to transcriptomic changes at &gt;500 target genes, and identify putative methylation-transcription factor interactions. Through Mendelian Randomisation, we infer causal effects of methylation on obesity and obesity-induced metabolic disturbances at 59 independent loci. Targeted methylation sequencing, CRISPR-activation and gene silencing in adipocytes, further identifies regional methylation variations, underlying regulatory elements and novel cellular metabolic effects. Our results indicate DNA methylation is an important determinant of human obesity and its metabolic complications, and reveal mechanisms through which altered methylation may impact adipocyte functions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-27T15:07:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007119","title":"RNA sequencing of a glioblastoma PDX cohort","description":"Patient-derived xenograft (PDX) models represent an essential tool for the preclinical evaluation of novel targeted therapies and their combinations. In this project, we molecularly characterized a comprehensive panel of glioma PDX models with well conserved molecular and pathological features over multiple passages. PDX samples were subjected to next generation sequencing (NGS). Characterization of cancer-relevant features including driver mutations or cellular processes was performed using mutational and gene expression data in order to identify potential biomarker or treatment targets in glioblastoma. In summary, we reported a newly established and molecularly characterized panel of glioma PDX models with high relevance for translational preclinical research.","abstract":"Patient-derived xenograft (PDX) models represent an essential tool for the preclinical evaluation of novel targeted therapies and their combinations. In this project, we molecularly characterized a comprehensive panel of glioma PDX models with well conserved molecular and pathological features over multiple passages. PDX samples were subjected to next generation sequencing (NGS). Characterization of cancer-relevant features including driver mutations or cellular processes was performed using mutational and gene expression data in order to identify potential biomarker or treatment targets in glioblastoma. In summary, we reported a newly established and molecularly characterized panel of glioma PDX models with high relevance for translational preclinical research.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-27T15:12:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007120","title":"Paired diagnostic and relapse medulloblastoma sequencing","description":"Whole exome and targeted panel sequencing in a cohort of paired diagnostic and relapse medulloblastoma samples.","abstract":"Whole exome and targeted panel sequencing in a cohort of paired diagnostic and relapse medulloblastoma samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-27T16:06:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007121","title":"Spatial genomic, biochemical, and cellular mechanisms drive meningioma heterogeneity and evolution","description":null,"abstract":"Intratumor heterogeneity underlies cancer evolution and treatment resistance1–5, but mechanisms driving intratumor heterogeneity that can be targeted to overcome treatment resistance are poorly understood. Meningiomas are the most common primary intracranial tumors and are resistant to all medical therapies6,7. High-grade meningiomas cause significant neurological morbidity and mortality and are distinguished from low-grade meningiomas by increased intratumor heterogeneity8. Here we integrate spatial transcriptomic and spatial protein profiling approaches across high-grade meningiomas to identify genomic and biochemical mechanisms linking intratumor heterogeneity to the molecular, temporal, and spatial evolution of cancer. We show divergent intratumor gene and protein expression programs distinguish high-grade meningiomas that are otherwise grouped together by current clinical classification systems. Analyses of matched pairs of primary and recurrent meningiomas reveal spatial expansion of subclonal copy number variants underlies treatment resistance and tumor recurrence. To translate these findings to clinical practice, we use epigenetic editing and lineage tracing approaches in human meningioma organoid models to identify molecular therapy combinations that target intratumor heterogeneity and block tumor growth. Our results establish a new foundation for personalized medical therapy to treat patients with high-grade meningiomas and provide a framework for understanding mechanisms and therapeutic vulnerabilities driving cancer heterogeneity and evolution.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007122","title":"Molecular profiling identifies at least 3 distinct types of post-transplant lymphoproliferative disorder involving CNS","description":null,"abstract":"Post-transplant lymphoproliferative disorder (PTLD) involving the central nervous system (CNS) is a rare complication of transplantation. Robust histopathologic prognostic biomarkers and the genomic landscape of PTLD with CNS involvement have yet to be defined. In this multi-institutional study, we performed clinicopathologic examination, targeted next-generation DNA sequencing (NGS), and chromosomal copy number analysis on a cohort of 24 patients with PTLD involving the CNS. Twenty-one patients had PTLD with exclusive CNS involvement, whereas three also had involvement of other systemic sites. We identified three distinct types of PTLD involving the CNS: 1) Sporadic primary CNS large B-cell lymphoma-like (EBV-negative) with MYD88 and CD79B mutations similar to EBV-negative primary CNS-DLBCL in immunocompetent adult patients; 2) Systemic Ras-driven with HRAS or NRAS mutations with both systemic and CNS involvement; 3) EBV-driven CNS-limited type with lack of systemic involvement, EBV-positivity, and an absence of oncogenic alterations. Pathologic evaluation identified Ki-67 labeling index &gt;80% and mean mitotic count &gt;2 per high power field as significant prognostic factors associated with worse overall survival in all PTLD cases, as well as in patients with EBV-positive PTLD with exclusive CNS involvement. Together, we reveal that PTLD involving the CNS is a heterogenous disease category that consists of at least three types based on integration of molecular alterations, EBV status, and presence or absence of extra-CNS systemic involvement, which we speculate are biologically distinct and might necessitate different treatments.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007123","title":"RNA-Seq of clonal endocrine therapy resistant cell lines","description":null,"abstract":"We barcoded endocrine therapy sensitive cell lines (MCF7 and T47D) and rendered them resistant to commonly applied first line endocrine therapeutics (Tamoxifen and estrogen deprivation). Next, we isolated single cell clones of endocrine therapy resistant populations and subjected clonal cell lines to RNA-Seq.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007124","title":"RNA-Seq on GeparSixto tissue samples","description":"RNA-Seq on GeparSixto tissue samples","abstract":"RNA-Seq on GeparSixto tissue samples","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-28T10:48:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007125","title":"T-cell receptor sequencing of tumor-infiltrating lymphocytes (TIL) in breast cancer","description":"The spatial distribution of tumor-infiltrating lymphocytes (TIL) predicts breast cancer outcome and response to systemic therapy, highlighting the importance of an intact tissue structure for characterizing patients’ tumors. Here, we present ST-FFPE, a spatial transcriptomics method for the analysis of formalin-fixed paraffin-embedded samples, which opens the possibility of interrogating widely available archival tissue. The method involves extraction, exome capture and sequencing of RNA from different tumor compartments microdissected by laser-capture, and can be used to study the cellular composition of various tumor environments. Focusing on triple-negative breast cancer (TNBC), we characterized T cells, B cells, dendritic cells, fibroblasts and endothelial cells in both stromal and intra-epithelial compartments. We found a highly variable spatial distribution of immune cell subsets among tumors. This analysis revealed that the immune repertoires of intra-epithelial T and B cells were consistently less diverse than those of stromal T and B cells. T-cell receptor (TCR) sequencing confirmed a reduced diversity and revealed higher clonality of intra-epithelial T cells relative to the corresponding stromal T cells. Analysis of the top ten dominant clonotypes in the two compartments showed a majority of shared but also some unique clonotypes both in stromal and intra-epithelial T cells. Hyperexpanded clonotypes were more abundant among intra-epithelial than stromal T cells. These findings validate the ST-FFPE method and suggest an accumulation of antigen-specific T cells within tumor core. Because ST-FFPE is readily applicable for analysis of previously collected tissue samples, it could be useful for rapid assessment of intratumoral cellular heterogeneity in multiple disease and treatment settings.","abstract":"The spatial distribution of tumor-infiltrating lymphocytes (TIL) predicts breast cancer outcome and response to systemic therapy, highlighting the importance of an intact tissue structure for characterizing patients’ tumors. Here, we present ST-FFPE, a spatial transcriptomics method for the analysis of formalin-fixed paraffin-embedded samples, which opens the possibility of interrogating widely available archival tissue. The method involves extraction, exome capture and sequencing of RNA from different tumor compartments microdissected by laser-capture, and can be used to study the cellular composition of various tumor environments. Focusing on triple-negative breast cancer (TNBC), we characterized T cells, B cells, dendritic cells, fibroblasts and endothelial cells in both stromal and intra-epithelial compartments. We found a highly variable spatial distribution of immune cell subsets among tumors. This analysis revealed that the immune repertoires of intra-epithelial T and B cells were consistently less diverse than those of stromal T and B cells. T-cell receptor (TCR) sequencing confirmed a reduced diversity and revealed higher clonality of intra-epithelial T cells relative to the corresponding stromal T cells. Analysis of the top ten dominant clonotypes in the two compartments showed a majority of shared but also some unique clonotypes both in stromal and intra-epithelial T cells. Hyperexpanded clonotypes were more abundant among intra-epithelial than stromal T cells. These findings validate the ST-FFPE method and suggest an accumulation of antigen-specific T cells within tumor core. Because ST-FFPE is readily applicable for analysis of previously collected tissue samples, it could be useful for rapid assessment of intratumoral cellular heterogeneity in multiple disease and treatment settings.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-28T14:24:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007126","title":"GM adipose tissue study","description":"The Greek Metabolic (GM) adipose study was carried out in 106 individuals living in Greece and consists of genotyping data (chip), RNA-Seq and ATAC-Seq (for a subset of individuals) data from paired biopsies of Subcutaneous and Visceral adipose tissue. eQTL mapping was performed to study gene regulation and findings compared to those from adipose tissue GTEX data. The focus of this project was to study an underexplored population living in different environmental conditions in order to reveal novel regulatory effects for genes that shape complex traits and disease risk. Our results highlight the utility of modest-sized studies in adding to our understanding of the molecular basis of complex traits and to the identification of mechanisms that drive disease in specific tissues.","abstract":"The Greek Metabolic (GM) adipose study was carried out in 106 individuals living in Greece and consists of genotyping data (chip), RNA-Seq and ATAC-Seq (for a subset of individuals) data from paired biopsies of Subcutaneous and Visceral adipose tissue. eQTL mapping was performed to study gene regulation and findings compared to those from adipose tissue GTEX data. The focus of this project was to study an underexplored population living in different environmental conditions in order to reveal novel regulatory effects for genes that shape complex traits and disease risk. Our results highlight the utility of modest-sized studies in adding to our understanding of the molecular basis of complex traits and to the identification of mechanisms that drive disease in specific tissues.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-29T13:33:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007127","title":"Human lymphoma plasma cfRNA - raw data","description":"This study contains total RNA sequencing data from plasma of 65 different human donors: 30 diffuse large B-cell lymphoma patients, 13 primary mediastinal large B-cell lymphoma patients and 22 cancer-free controls.","abstract":"This study contains total RNA sequencing data from plasma of 65 different human donors: 30 diffuse large B-cell lymphoma patients, 13 primary mediastinal large B-cell lymphoma patients and 22 cancer-free controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-30T15:13:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007128","title":"Spatial and temporal transcriptomics of medulloblastoma with chromothripsis identifies multiple genetic clones that resist to treatment and lead to relapse","description":"From all paediatric brain tumours, medulloblastomas with chromothripsis, a form of genome instability leading to massive genome rearrangements, are particularly aggressive. To dissect the complex biology underlying the aggressiveness of chromothriptic medulloblastomas, we applied spatial transcriptomics to i) chromothriptic and non-chromothriptic medulloblastomas from the same molecular subgroup (n=13) and ii) patient-derived xenografts from chromothriptic medulloblastoma, from the minimal residual disease stage to regrown tumours (n=11). Chromothriptic medulloblastomas showed higher spatial intra-tumour heterogeneity, proliferation and stemness, but lower immune infiltration and differentiation, as compared with non-chromothriptic medulloblastomas. Spatial mapping of genetic clones identified phenotypic features such as degree of differentiation, proliferation and immune infiltration enriched in specific clones. Cells from multiple genetic clones resisted treatment and gave rise to relapse in patient-derived xenografts of chromothriptic medulloblastoma. We identified a potential role of tumour microtubes in treatment resistance in chromothriptic medulloblastoma.","abstract":"From all paediatric brain tumours, medulloblastomas with chromothripsis, a form of genome instability leading to massive genome rearrangements, are particularly aggressive. To dissect the complex biology underlying the aggressiveness of chromothriptic medulloblastomas, we applied spatial transcriptomics to i) chromothriptic and non-chromothriptic medulloblastomas from the same molecular subgroup (n=13) and ii) patient-derived xenografts from chromothriptic medulloblastoma, from the minimal residual disease stage to regrown tumours (n=11). Chromothriptic medulloblastomas showed higher spatial intra-tumour heterogeneity, proliferation and stemness, but lower immune infiltration and differentiation, as compared with non-chromothriptic medulloblastomas. Spatial mapping of genetic clones identified phenotypic features such as degree of differentiation, proliferation and immune infiltration enriched in specific clones. Cells from multiple genetic clones resisted treatment and gave rise to relapse in patient-derived xenografts of chromothriptic medulloblastoma. We identified a potential role of tumour microtubes in treatment resistance in chromothriptic medulloblastoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-30T15:42:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007129","title":"DERMATLAS__Trichoblastoma_and_Trichoepithelioma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Trichoblastomas and Trichoepitheliomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Trichoblastomas and Trichoepitheliomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007130","title":"DERMATLAS__Trichoblastoma_and_Trichoepithelioma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Trichoblastomas and Trichoepitheliomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Trichoblastomas and Trichoepitheliomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007131","title":"Archaeogenomic distinctiveness of the Isthmo-Colombian area","description":null,"abstract":"Ancient Isthmian genomes address anthropological questions on pre-contact burials.\nThe comparison with modern Panamanians highlights genomic structure on the Isthmus.\nA genomic component drives the Isthmian groups on a distinctive variability axis.\nA previously unknown Pleistocene ancestry identified in the Isthmo-Colombian area.","study_type":"Forensic or Paleo-genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-31T13:54:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007132","title":"DERMATLAS__Trichoadenoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Trichoadenomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Trichoadenomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007133","title":"DERMATLAS__Trichoadenoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Trichoadenomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Trichoadenomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007134","title":"DERMATLAS__Trichofolliculoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Trichofolliculomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Trichofolliculomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007135","title":"DERMATLAS__Trichofolliculoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Trichofolliculomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Trichofolliculomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007136","title":"T cell receptor repertoire sequencing reveals chemotherapy-driven clonal expansion in colorectal liver metastases","description":"Colorectal liver metastasis (CLM) is a leading cause of colorectal cancer mortality, and the response to immune checkpoint inhibition (ICI) in microsatellite stable CRC has been disappointing. Administration of cytotoxic chemotherapy may cause increased density of tumour infiltrating T cells, which has been associated with improved response to ICI. This study aimed to quantify and characterize T cell infiltration in CLM using T cell receptor (TCR) repertoire sequencing. Eighty-five resected CLM from patients included in the Oslo CoMet study were subjected to TCR repertoire sequencing. Thirty-five and 15 patients had received neoadjuvant chemotherapy (NACT) within a short or long interval, respectively, prior to resection, while 35 patients had not been exposed to NACT. T cell fractions were calculated, repertoire clonality was analysed based on Hill evenness curves, and TCR sequential convergence was assessed using network analysis.\nIncreased T cell fractions (10.6% vs 6.3%) were detected in CLM exposed to NACT within a short interval prior to resection, while modestly increased clonality was observed in NACT exposed tumours independently of the timing of NACT administration and surgery. While private clones made up &gt;90% of detected clones, network connectivity analysis revealed that public clones contributed the majority of TCR sequence convergence.\nTCR repertoire sequencing can be used to quantify T cell infiltration and clonality in clinical samples. This study provides evidence to support chemotherapy-driven T cell clonal expansion in CLM in a clinical context.","abstract":"Colorectal liver metastasis (CLM) is a leading cause of colorectal cancer mortality, and the response to immune checkpoint inhibition (ICI) in microsatellite stable CRC has been disappointing. Administration of cytotoxic chemotherapy may cause increased density of tumour infiltrating T cells, which has been associated with improved response to ICI. This study aimed to quantify and characterize T cell infiltration in CLM using T cell receptor (TCR) repertoire sequencing. Eighty-five resected CLM from patients included in the Oslo CoMet study were subjected to TCR repertoire sequencing. Thirty-five and 15 patients had received neoadjuvant chemotherapy (NACT) within a short or long interval, respectively, prior to resection, while 35 patients had not been exposed to NACT. T cell fractions were calculated, repertoire clonality was analysed based on Hill evenness curves, and TCR sequential convergence was assessed using network analysis.\nIncreased T cell fractions (10.6% vs 6.3%) were detected in CLM exposed to NACT within a short interval prior to resection, while modestly increased clonality was observed in NACT exposed tumours independently of the timing of NACT administration and surgery. While private clones made up &gt;90% of detected clones, network connectivity analysis revealed that public clones contributed the majority of TCR sequence convergence.\nTCR repertoire sequencing can be used to quantify T cell infiltration and clonality in clinical samples. This study provides evidence to support chemotherapy-driven T cell clonal expansion in CLM in a clinical context.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-03-31T14:16:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007137","title":"DERMATLAS__Apocrine_carcinoma_skin_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Apocrine carcinomas of the skin.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Apocrine carcinomas of the skin.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007138","title":"DERMATLAS__Apocrine_carcinoma_skin_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Apocrine carcinomas of the skin.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Apocrine carcinomas of the skin.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007139","title":"COVRES-NI-UU-Genomics: Understanding the host-virus response in non-hospitalised versus hospitalised patients","description":null,"abstract":"The SARS-CoV-2 (COVID19) pandemic continues globally and a better understanding of the drivers of disease severity and how to treat COVID-19 are desperately needed. It is unclear why some infected individuals experience mild symptoms, while others experience severe symptoms with rapid disease progression and death in the worst cases. The COVRES project aims to generate patient genomic data and other biological and clinical features to stratify SARS-CoV-2 positive patients by disease severity risk (non-hospitalised versus hospitalised). This study involved RNA sequencing of PCR confirmed SARS-CoV-2 positive patients recruited in Northern Ireland by Personalised Medicine Centre, School of Medicine, Ulster University.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007140","title":"COVRES-NI-UU-RNASeq: Understanding the host-virus response in non-hospitalised versus hospitalised patients","description":null,"abstract":"The SARS-CoV-2 (COVID19) pandemic continues globally and a better understanding of the drivers of disease severity and how to treat COVID-19 are desperately needed. It is unclear why some infected individuals experience mild symptoms, while others experience severe symptoms with rapid disease progression and death in the worst cases. The COVRES project aims to generate patient genomic data and other biological and clinical features to stratify SARS-CoV-2 positive patients by disease severity risk (non-hospitalised versus hospitalised). This study involved RNA sequencing of PCR confirmed SARS-CoV-2 positive patients recruited in Northern Ireland by Personalised Medicine Centre, School of Medicine, Ulster University.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007141","title":"Prospective cohort of patients with Multiple Sclerosis and controls","description":"The Sys4MS cohort comprises 350 patients with Multiple Sclerosis and 90 healthy controls with 2 years of follow-up. The following variables are available at baseline assessment: demographics, clinical scales, disease subtype and duration, MS therapies, brain MRI (volumetry and lesion load), retinal thicknesses by OCT, GWAS, cytomics, and phosphoproteomics. At the end of the follow-up 2 years later, the variables available are clinical scales, classification as NEDA and disease progression, brain MRI and retinal thicknesses.","abstract":"The Sys4MS cohort comprises 350 patients with Multiple Sclerosis and 90 healthy controls with 2 years of follow-up. The following variables are available at baseline assessment: demographics, clinical scales, disease subtype and duration, MS therapies, brain MRI (volumetry and lesion load), retinal thicknesses by OCT, GWAS, cytomics, and phosphoproteomics. At the end of the follow-up 2 years later, the variables available are clinical scales, classification as NEDA and disease progression, brain MRI and retinal thicknesses.","study_type":"Other","pubmed_ids":[35658739,35772194],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007142","title":"Prospective cohort of patients with Multiple Sclerosis","description":"The Sys4MS cohort comprises 350 patients with MS and 90 controls with 2 years of follow-up. At baseline, the following information is available: demographics, clinical scales, disease subtype, disease duration, use of disease-modifying drugs, brain MRI (volumetry and lesion load), retinal thicknesses by OCT, GWAS, cytometry, and phosphoproteomics. At the end of the follow-up, the information available is clinical scales, disease progression, NEDA, brain MRI, and OCT.","abstract":"The Sys4MS cohort comprises 350 patients with MS and 90 controls with 2 years of follow-up. At baseline, the following information is available: demographics, clinical scales, disease subtype, disease duration, use of disease-modifying drugs, brain MRI (volumetry and lesion load), retinal thicknesses by OCT, GWAS, cytometry, and phosphoproteomics. At the end of the follow-up, the information available is clinical scales, disease progression, NEDA, brain MRI, and OCT.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007143","title":"Persister cell phenotypes contribute to poor patient outcomes after neoadjuvant chemotherapy in PDAC (Hipo_015)","description":null,"abstract":"Neoadjuvant chemotherapy can improve the survival of patients with borderline and unresectable pancreatic ductal adenocarcinoma (PDAC), however, heterogeneous responses to chemotherapy remain a significant clinical challenge. Here, we performed RNAseq (n=97) and multiplexed immunofluorescence (n=122) on chemo-naïve and post-chemotherapy (post-CTX) resected patient samples (chemoradiotherapy excluded) to define the molecular and cellular impact of neoadjuvant chemotherapy. Transcriptome analysis combined with high resolution mapping of whole tissue sections identified GATA6 (Classical), KRT17 (Basal-like) and Cytochrome P450 3A (CYP3A) co-expressing cells that were preferentially enriched in post-CTX resected samples. The persistence of GATA6Hi and KRT17Hi cells post-CTX was significantly associated with poor survival after mFOLFIRINOX (mFFX), but not gemcitabine. Analysis of organoid models derived from chemo-naïve and post-CTX samples, demonstrated that CYP3A expression is a predictor of chemotherapy response and that CYP3A-expressing drug detoxification pathways can metabolize the prodrug irinotecan, a constituent of mFFX. Taken together, these findings identify CYP3A-expressing drug-resistant cell phenotypes in residual disease that may ultimately inform adjuvant treatment selection.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-03T08:28:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007144","title":"IL7-receptor expression is frequent in T-cell acute lymphoblastic leukemia and predicts sensitivity to JAK-inhibition","description":"T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a dismal prognosis related to refractory/relapsing diseases, raising the need for new targeted-therapies. Activating mutations of the IL7-receptor pathway genes (IL7Rp) play a proven leukemia-supportive role in T-ALL. JAK-inhibitors such as ruxolitinib have recently demonstrated preclinical efficacy. However, prediction markers for sensitivity to JAK-inhibitors are still lacking. Herein, we show that IL7R (CD127) expression is more frequent (~70%) than IL7Rp-mutations in T-ALL (~30%). We compared the so-called non-expressers (no IL7R-expression/IL7Rp-mutation), expressers (IL7R-expression without IL7Rp-mutation) and mutants (IL7Rp-mutations). Integrative multi-omics analysis outlined IL7R-deregulation in virtually all T-ALL subtypes, at the epigenetic-level in non-expressers, genetic-level in mutants, and post-transcriptional level in expressers. Ex-vivo data using primary-derived xenografts support that IL7Rp is functional whenever the IL7R is expressed, regardless of the IL7Rp mutational status. Consequently, ruxolitinib impaired T-ALL survival in both expressers and mutants. Interestingly, we show that expressers displayed ectopic IL7R-expression and IL7Rp-addiction conferring a deeper sensitivity to ruxolitinib. Conversely, mutants were more sensitive to venetoclax than expressers. Overall, combination of ruxolitinib and venetoclax resulted in synergistic effects in both groups. We illustrate the clinical relevance of this association by reporting achievement of complete remission in two patients with refractory/relapsed-T-ALL. This provides proof of concept for translation of this strategy into clinics as bridge to transplant. Altogether, IL7R-expression can be used as a biomarker for sensitivity to JAK-inhibition, thereby expanding the fraction of T-ALL patients eligible to ruxolitinib up to nearly ~70% of T-ALL.","abstract":"T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a dismal prognosis related to refractory/relapsing diseases, raising the need for new targeted-therapies. Activating mutations of the IL7-receptor pathway genes (IL7Rp) play a proven leukemia-supportive role in T-ALL. JAK-inhibitors such as ruxolitinib have recently demonstrated preclinical efficacy. However, prediction markers for sensitivity to JAK-inhibitors are still lacking. Herein, we show that IL7R (CD127) expression is more frequent (~70%) than IL7Rp-mutations in T-ALL (~30%). We compared the so-called non-expressers (no IL7R-expression/IL7Rp-mutation), expressers (IL7R-expression without IL7Rp-mutation) and mutants (IL7Rp-mutations). Integrative multi-omics analysis outlined IL7R-deregulation in virtually all T-ALL subtypes, at the epigenetic-level in non-expressers, genetic-level in mutants, and post-transcriptional level in expressers. Ex-vivo data using primary-derived xenografts support that IL7Rp is functional whenever the IL7R is expressed, regardless of the IL7Rp mutational status. Consequently, ruxolitinib impaired T-ALL survival in both expressers and mutants. Interestingly, we show that expressers displayed ectopic IL7R-expression and IL7Rp-addiction conferring a deeper sensitivity to ruxolitinib. Conversely, mutants were more sensitive to venetoclax than expressers. Overall, combination of ruxolitinib and venetoclax resulted in synergistic effects in both groups. We illustrate the clinical relevance of this association by reporting achievement of complete remission in two patients with refractory/relapsed-T-ALL. This provides proof of concept for translation of this strategy into clinics as bridge to transplant. Altogether, IL7R-expression can be used as a biomarker for sensitivity to JAK-inhibition, thereby expanding the fraction of T-ALL patients eligible to ruxolitinib up to nearly ~70% of T-ALL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-03T16:37:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007145","title":"The Sys4MS cohort: a prospective cohort of patients with Multiple Sclerosis and omics","description":null,"abstract":"The sys4MS cohort comprises 350 patients with Multiple Sclerosis (MS) and 9 controls, with 2 years of follow-up. Baseline data includes demographics, clinical scales, disease duration and subtype and use of disease-modifying drugs, brain MRI (volumetry and lesion load), retinal thickness by OCT, genomics (GWAS), cytomics, and phosphoproteomics. Data at the end of follow-up includes clinical scales, brain MRI and OCT.","study_type":"Other","pubmed_ids":[32139439,35658739,35772194],"external_links":null,"is_released":true,"released_date":"2023-04-03T21:14:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007146","title":"Molecular analysis of cancer genomes in children with Lynch syndrome: exploring causal associations","description":"Lynch syndrome (LS) predisposes to cancer in adulthood and is caused by heterozygous germline variants in a mismatch repair (MMR) gene. Recent studies show an increased prevalence of LS among children with cancer, suggesting a causal relationship. For LS-spectrum (LSS) cancers, including high-grade gliomas and colorectal cancer, causality has been supported by typical MMR-related tumor characteristics, but for non-LSS cancers, causality is unclear. This dataset contains 5 patients with Lynch Syndrome from the INFORM registry.","abstract":"Lynch syndrome (LS) predisposes to cancer in adulthood and is caused by heterozygous germline variants in a mismatch repair (MMR) gene. Recent studies show an increased prevalence of LS among children with cancer, suggesting a causal relationship. For LS-spectrum (LSS) cancers, including high-grade gliomas and colorectal cancer, causality has been supported by typical MMR-related tumor characteristics, but for non-LSS cancers, causality is unclear. This dataset contains 5 patients with Lynch Syndrome from the INFORM registry.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-04T10:59:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007147","title":"Convergent evolution drives therapy resistance in DNA repair-deficient mCRPC","description":"These are FASTQ files obtained from RNA-sequencing and DNA-sequencing of tumor biopsies obtained from metastatic castration-resistant prostate tumors. Patients were treated with multiple lines of therapy with samples obtained at the time of rapid autopsy following the CASCADE protocol. Multiple biopsies were obtained from each patient under guidance of pathology. DNA were analyzed by high-depth whole genome, exome, and targeted sequencing. RNA were analyzed using a Nugen amplification protocol as described in Quigley Cell 2018.","abstract":"These are FASTQ files obtained from RNA-sequencing and DNA-sequencing of tumor biopsies obtained from metastatic castration-resistant prostate tumors. Patients were treated with multiple lines of therapy with samples obtained at the time of rapid autopsy following the CASCADE protocol. Multiple biopsies were obtained from each patient under guidance of pathology. DNA were analyzed by high-depth whole genome, exome, and targeted sequencing. RNA were analyzed using a Nugen amplification protocol as described in Quigley Cell 2018.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-04T22:59:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007148","title":"IBD_RESPONSE_Metagenomics__PREDICCT_","description":"Prognostic effect of Environmental factors in Crohn’s and Colitis Study (PREdiCCt) is a study of patients with Crohn’s disease and ulcerative colitis recruited in clinical remission and followed over 24-48m under the point of flare or no-flare. Stool samples have been collected at baseline and at flare. Samples have had microbial DNA extracted at University of Edinburgh and will be transferred to Sanger Institute for metagenomic sequencing. Data from these samples will be used as controls to validate metagenomic data that will be collected as part of the IBD-RESPONSE project.","abstract":"The IBD RESPONSE study will collect host genetic and stool microbiome profiles at multiple time-points across 1125 inflammatory bowel disease (IBD) patients upon their first treatment with either anti-TNF or anti-integrin biological therapy (including an estimated 1500 treatment episodes). This project will also include a significant replication dataset, using new treatment episodes in microbiome samples already collected by the cross-sectional PREdiCCt cohort. The primary aims of this research are to identify microbial predictors of treatment response (including bacterial species and microbial functional pathways), to establish whether different microbes may predict success or failure of different biological therapies, and to establish the predictive power of the microbiome in treatment response.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007149","title":"HG_TP11057_Prognostic_effect_of_Environmental_factors_in_Crohn_s_and_Colitis_Study__PREdiCCt_","description":"1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"PREdiCCt is a study of patients with Crohn’s disease and ulcerative colitis recruited in clinical remission and followed over 24-48m under the point of flare or no-flare. Stool samples have been collected at baseline and at flare. Samples have had microbial DNA extracted at University of Edinburgh and are stored pending transfer to Sanger Institute for metagenomic sequencing. Following metagenomic sequencing and quality control of the Institution’s Material, Sanger will provide data to the Institution.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007150","title":"CD_METARESPONSE_Metagenomics","description":"CD-metaRESPONSE study is a sub-study of the IBD-RESPONSE study. It is a large-scale metagenomics and metabonomics study run by the IBD BioResource which aims to identify predictors of biologic (especially anti-TNF, but (especially anti-TNF, but including ustekinumab and vedolizumab) treatment response and develop a decision-support algorithm based on microbes, their metabolites, genomic signatures and clinical data.","abstract":"The CD-METARESPONSE study will collect host genetic and stool microbiome profiles at multiple time-points across 200 patients upon their first treatment with either anti-TNF or anti-integrin biological therapy .The primary aims of this research are to identify microbial predictors of treatment response (including bacterial species and microbial functional pathways), to establish whether different microbes may predict success or failure of different biological therapies, and to establish the predictive power of the microbiome in treatment response.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007151","title":"HCA_Gut_Paediatric_Hirschsprung_s_disease_Teichmann_RNA_Managed_Access_","description":"This study involves atlasing the development of the postnatal gut nervous system in order to elucidate the pathogenic mechanisms of Hirschsprung disease.","abstract":"Hirschsprung’s disease (HD) is congenital condition where the enteric neurons and glia are absent in parts of the bowel. HD is a genetic disease in which enteric ganglia development is implicated. Currently, the interplay between causal HD genes and development of the enteric neuron system remains obscure. Here, we will combine whole genome sequencing, single nuclei multiomic analysis (10x multiome, scRNA+scATAC) and spatial transcriptomics analysis on frozen HD and healthy colonic tissue to uncover the mechanisms of HD pathogenesis","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-05T14:36:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007152","title":"HCA_Gut_Paediatric_Hirschsprung_s_disease_Teichmann_Spatial_Managed_Access_","description":"This study involves atlasing the development of the postnatal gut nervous system in order to elucidate the pathogenic mechanisms of Hirschsprung disease.","abstract":"Hirschsprung’s disease (HD) is congenital condition where the enteric neurons and glia are absent in parts of the bowel. HD is a genetic disease in which enteric ganglia development is implicated. Currently, the interplay between causal HD genes and development of the enteric neuron system remains obscure. Here, we will combine spatial transcriptomics analysis on frozen HD and healthy colonic tissue, whole genome sequencing and single nuclei multiomic analysis (10x multiome, scRNA+scATAC) to uncover the mechanisms of HD pathogenesis.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-05T15:07:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007153","title":"DDD_GSA_Genotyping","description":"This study involved genotyping ~3300 parent-offspring trios from the Deciphering Developmental Disorders study on the Illumina Global Screening Array. The goal was to use these data to investigate the polygenic contribution to neurodevelopmental disorders.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This study involved genotyping ~3300 parent-offspring trios from the Deciphering Developmental Disorders study on the Illumina Global Screening Array. The goal was to use these data to investigate the polygenic contribution to neurodevelopmental disorders.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007154","title":"Exome-wide study of renal operational tolerance - Illumina 2000","description":null,"abstract":"We performed an exome-wide association study comparing the distribution of moderate to high impact variants in 36 tolerant patients (with Illumina 1500 and Illumina 2000), selected for genetic homogeneity using principal component analysis, and 192 controls, using an optimal sequence-kernel association test adjusted for small samples.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007155","title":"Exome-wide study of renal operational tolerance - Illumina 1500","description":null,"abstract":"We performed an exome-wide association study comparing the distribution of moderate to high impact variants in 36 tolerant patients (with Illumina 1500 and Illumina 2000), selected for genetic homogeneity using principal component analysis, and 192 controls, using an optimal sequence-kernel association test adjusted for small samples.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007156","title":"Cachexia - Non-Cachexia Metagenome Analysis","description":"Cancer cachexia has been linked to gut bacterial alterations, but alterations of gut viruses, mostly bacteriophages, have not yet been explored. We performed shotgun metagenomic sequencing of DNA from stool samples of 78 cachectic and 42 non-cachectic cancer patients. K-mer-based matching to reference databases revealed abundance variations of bacteria and viruses. Beyond bacterial alterations, cachectic patients exhibited significantly lower bacteriophage abundance, predominantly affecting Caudovirales and Siphoviridae species (double-stranded DNA) but also Inoviridae and Microviridae families (single-stranded DNA).","abstract":"Cancer cachexia has been linked to gut bacterial alterations, but alterations of gut viruses, mostly bacteriophages, have not yet been explored. We performed shotgun metagenomic sequencing of DNA from stool samples of 78 cachectic and 42 non-cachectic cancer patients. K-mer-based matching to reference databases revealed abundance variations of bacteria and viruses. Beyond bacterial alterations, cachectic patients exhibited significantly lower bacteriophage abundance, predominantly affecting Caudovirales and Siphoviridae species (double-stranded DNA) but also Inoviridae and Microviridae families (single-stranded DNA).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-07T17:04:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007157","title":"Elevated cfDNA after exercise is derived primarily from mature polymorphonuclear neutrophils, with a minor contribution of cardiomyocytes","description":null,"abstract":"Strenuous physical exercise causes a massive elevation in the concentration of circulating cell-free DNA (cfDNA), which correlates with effort intensity and duration. The cellular sources and physiological drivers of this phenomenon are unknown. Using methylation patterns of cfDNA and associated histones, we show that cfDNA in exercise originates mostly in extramedullary polymorphonuclear neutrophils. Strikingly, the concentration of cardiomyocyte cfDNA increases after a marathon, consistent with elevated troponin levels and indicating low-level, delayed cardiac cell death. Physical impact, low oxygen levels and elevated core body temperature contribute to the release of neutrophil cfDNA, while muscle contraction, increased heart rate, beta-adrenergic signaling or steroid treatment fail to cause elevation of cfDNA. Physical training reduces the release of neutrophil cfDNA after a standard exercise, revealing an inverse relationship between exercise-induced cfDNA release and training level. We speculate that the release of cfDNA from neutrophils in exercise relates to the activation of neutrophils in the context of exercise-induced muscle damage.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-08T19:55:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007158","title":"The Sys4MS cohort of patients with Multiple Sclerosis","description":"Prospective cohort of 350 MS patients and 90 Healthy Controls","abstract":"Prospective cohort of 350 MS patients and 90 Healthy Controls","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007159","title":"Evaluation of triple negative breast cancer with heterogeneous immune infiltration","description":"Identification of potential RNA markers fir TILs infiltration in patients with triple negative breast cancer with heterogeneous immune infiltration.","abstract":"Identification of potential RNA markers fir TILs infiltration in patients with triple negative breast cancer with heterogeneous immune infiltration.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-11T11:58:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007160","title":"Exploring high-throughput drug sensitivity testing in neuroblastoma cell lines and patient-derived tumor organoids in the era of precision medicine","description":"Despite druggable events in 80% of neuroblastoma patients within the Princess Máxima Center precision medicine program 'iTHER', clinical uptake of treatment recommendations has been low, and the clinical impact for individual patients remains hard to predict. This stresses the need for a method integrating genomics and transcriptomics with functional approaches into therapeutic decision making.\nWe aimed to launch an online repository integrating genomics and transcriptomics with high-throughput drug screening (HTS) of nineteen commonly used neuroblastoma cell lines and fourteen generated neuroblastoma patient-derived organoids (NBL-PDOs) to improve identification of molecularly matched therapies and support clinical uptake. Cell lines, NBL-PDOs and their parental tumors were characterized utilizing (lc)WGS, WES and RNAseq. Cells were exposed to a ~200 compound library, and viability was assessed using CellTiterGlo or MTT. Molecular and HTS results were transferred to the R2 platform (http://r2platform.com/pmc_nb_drugs/), in which a comprehensive suite of visualizations and analysis options were implemented.\nAs a result, a powerful reference set of cell lines is available, reflecting distinct known pharmacologic vulnerabilities, including resistance of TP53-inactivated lines to MDM2 inhibitor idasanutlin; ALK-inhibitor sensitivity in ALK-activated lines, and sensitivity of an ATM-deleted cell line to PARP- and CHEK1-inhibitors. Novel established NBL-PDOs retained molecular features of their parental tumor and again reflected established drug sensitivities. However, HTS also identified additional therapeutic vulnerabilities in vitro, such as a striking correlation between a positive mesenchymal signature and sensitivity to BCL2-inhibitor venetoclax. Finally, we explored personalized drug sensitivities within iTHER, demonstrating HTS can support genomic and transcriptomic results, thereby strengthening the rationale for clinical uptake. Furthermore, in vitro insensitivity may avoid ineffective treatments. Lastly, novel treatment options may be identified, as indicated by sensitivity to ponatinib correlating with overexpression of RET or KIT.\nIn conclusion, we established a dynamic publicly available dataset with detailed genomic, transcriptomic, and pharmacological annotation of classical neuroblastoma cell lines as well as NBL-PDOs, representing the heterogeneous landscape of neuroblastoma. We anticipate that in vitro drug screening will be complementary to genomic-guided precision medicine by supporting clinical decision making, thereby improving prognosis for all neuroblastoma patients in the future.","abstract":"Despite druggable events in 80% of neuroblastoma patients within the Princess Máxima Center precision medicine program 'iTHER', clinical uptake of treatment recommendations has been low, and the clinical impact for individual patients remains hard to predict. This stresses the need for a method integrating genomics and transcriptomics with functional approaches into therapeutic decision making.\nWe aimed to launch an online repository integrating genomics and transcriptomics with high-throughput drug screening (HTS) of nineteen commonly used neuroblastoma cell lines and fourteen generated neuroblastoma patient-derived organoids (NBL-PDOs) to improve identification of molecularly matched therapies and support clinical uptake. Cell lines, NBL-PDOs and their parental tumors were characterized utilizing (lc)WGS, WES and RNAseq. Cells were exposed to a ~200 compound library, and viability was assessed using CellTiterGlo or MTT. Molecular and HTS results were transferred to the R2 platform (http://r2platform.com/pmc_nb_drugs/), in which a comprehensive suite of visualizations and analysis options were implemented.\nAs a result, a powerful reference set of cell lines is available, reflecting distinct known pharmacologic vulnerabilities, including resistance of TP53-inactivated lines to MDM2 inhibitor idasanutlin; ALK-inhibitor sensitivity in ALK-activated lines, and sensitivity of an ATM-deleted cell line to PARP- and CHEK1-inhibitors. Novel established NBL-PDOs retained molecular features of their parental tumor and again reflected established drug sensitivities. However, HTS also identified additional therapeutic vulnerabilities in vitro, such as a striking correlation between a positive mesenchymal signature and sensitivity to BCL2-inhibitor venetoclax. Finally, we explored personalized drug sensitivities within iTHER, demonstrating HTS can support genomic and transcriptomic results, thereby strengthening the rationale for clinical uptake. Furthermore, in vitro insensitivity may avoid ineffective treatments. Lastly, novel treatment options may be identified, as indicated by sensitivity to ponatinib correlating with overexpression of RET or KIT.\nIn conclusion, we established a dynamic publicly available dataset with detailed genomic, transcriptomic, and pharmacological annotation of classical neuroblastoma cell lines as well as NBL-PDOs, representing the heterogeneous landscape of neuroblastoma. We anticipate that in vitro drug screening will be complementary to genomic-guided precision medicine by supporting clinical decision making, thereby improving prognosis for all neuroblastoma patients in the future.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-12T10:58:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007161","title":"Neuroblastoma tumors by bulk RNAseq, from Berlanga et al, 2022","description":"To prouve the relevance of the use of PDX models derived from patient's tumors.","abstract":"To prouve the relevance of the use of PDX models derived from patient's tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-12T14:06:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007162","title":"A GWAS of Progression in Multiple Sclerosis","description":"This is a genome wide association study (GWAS) of disease progression in multiple sclerosis (MS). The study involved a total of 12584 cases recruited from multiple centres around the world and tested at 7.8 million common autosomal single nucleotide variants. The data from the European cases (n=4853) are included in this EGA submission in 10 country specific data sub-sets.","abstract":"This is a genome wide association study (GWAS) of disease progression in multiple sclerosis (MS). The study involved a total of 12584 cases recruited from multiple centres around the world and tested at 7.8 million common autosomal single nucleotide variants. The data from the European cases (n=4853) are included in this EGA submission in 10 country specific data sub-sets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-12T15:26:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007163","title":"Oesophageal_Adenocarcinoma_Organoid_PacBio","description":"PacBio Sequencing of 6 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical resection of the tumour. All model derivations took place with the CGaP facility in Sanger.  This PacBio data will be combined with other sequencing data in order to generate accurate reference cancer genomes.","abstract":"There is complex interplay between underlying genetic sequence and epigenetic factors, however this interplay is still illusive. Massively reconstructed cancer genomes can be used in order to better understand this relationship. Six oesophageal adenocarcinoma organoids will be sequenced using long read sequencing technologies and will be profiled for a range of epigenetic marks. Combination of genetic and epigenetic data will allow the thorough characterisation of reference cancer genomes and will provide novel insights into mechanisms of gene regulation.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-13T09:09:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007164","title":"Spatial and temporal intra-tumoural heterogeneity in advanced High-Grade Serous Ovarian Cancer: implications for surgical and clinical outcomes","description":"Limited evidence exists on the extent and impact of spatial and temporal heterogeneity of high grade serous ovarian cancer (HGSOC) on tumour evolution and patients surgical and clinical outcome. We investigated this through systematic mapping of multi-site tumours at initial presentation and matched relapse from 49 chemo-naïve HGSOC patients with high tumour load, operated upfront. \nOur data provides a unique insight into the tumour evolution and metastatic pathways of HGSOC across time and space, how this\ncomplexity relates to surgical and clinical outcome and its consequences on clinical decision-making.","abstract":"Limited evidence exists on the extent and impact of spatial and temporal heterogeneity of high grade serous ovarian cancer (HGSOC) on tumour evolution and patients surgical and clinical outcome. We investigated this through systematic mapping of multi-site tumours at initial presentation and matched relapse from 49 chemo-naïve HGSOC patients with high tumour load, operated upfront. \nOur data provides a unique insight into the tumour evolution and metastatic pathways of HGSOC across time and space, how this\ncomplexity relates to surgical and clinical outcome and its consequences on clinical decision-making.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-13T11:59:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007165","title":"RNAseq","description":"Familial Mediterranean Fever (FMF) is a prototypical periodic fever syndrome caused by genetic variation in MEFV. While it is known that especially IL-1β responses are dysregulated in FMF, its innate immune landscape has not been comprehensively described. Therefore, we extensively characterized the function of monocytes and neutrophils in patients with FMF in between disease attacks, as well as their circulating inflammatory proteome. We found that monocyte IL-1 and IL-6 production was enhanced following a range of stimulations, in concordance with alterations in the plasma inflammatory proteome. In contrast, neutrophil function in FMF was normal. Additionally, ATAC-seq and RNA-seq analyses revealed important epigenetic and transcriptional reprogramming arguing for monocyte function dysregulation. Interestingly, chromatin-accessibility was down-regulated in genomic regions related to cellular responses. This argues that the primary immune dysregulation in monocytes due to MEFV mutations leads to a chronic inflammatory profile that is subsequently associated with counterregulatory epigenetic and transcriptional changes reminiscent of tolerance (rather than trained immunity) induction. These data increase our understanding of the innate immune changes in FMF, that can be used in the design of novel approaches to manage chronic inflammation of these patients.","abstract":"Familial Mediterranean Fever (FMF) is a prototypical periodic fever syndrome caused by genetic variation in MEFV. While it is known that especially IL-1β responses are dysregulated in FMF, its innate immune landscape has not been comprehensively described. Therefore, we extensively characterized the function of monocytes and neutrophils in patients with FMF in between disease attacks, as well as their circulating inflammatory proteome. We found that monocyte IL-1 and IL-6 production was enhanced following a range of stimulations, in concordance with alterations in the plasma inflammatory proteome. In contrast, neutrophil function in FMF was normal. Additionally, ATAC-seq and RNA-seq analyses revealed important epigenetic and transcriptional reprogramming arguing for monocyte function dysregulation. Interestingly, chromatin-accessibility was down-regulated in genomic regions related to cellular responses. This argues that the primary immune dysregulation in monocytes due to MEFV mutations leads to a chronic inflammatory profile that is subsequently associated with counterregulatory epigenetic and transcriptional changes reminiscent of tolerance (rather than trained immunity) induction. These data increase our understanding of the innate immune changes in FMF, that can be used in the design of novel approaches to manage chronic inflammation of these patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-13T12:28:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007166","title":"ATACseq","description":"ATACseq data for this study.","abstract":"ATACseq data for this study.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-13T12:28:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007167","title":"Transcriptomic classes of BCR-ABL1 lymphoblastic leukemia","description":"In BCR-ABL1 lymphoblastic leukemia, treatment heterogeneity to tyrosine kinase inhibitors (TKIs), especially in the absence of kinase domain mutations in BCR-ABL1, is poorly understood. Through deep molecular profiling, we uncovered three transcriptomic subtypes of BCR-ABL1 lymphoblastic leukemia, each representing a maturation arrest at a stage of B-cell progenitor differentiation. An earlier arrest was associated with lineage promiscuity, treatment refractoriness, and poor patient outcomes. A later arrest was associated with lineage fidelity, deep and durable leukemia remissions, and improved patient outcomes. Each maturation arrest was marked by specific genomic events that control different transition points in B-cell development. Interestingly, these events were absent in BCR-ABL1+ pre-leukemic stem cells isolated from patients regardless of subtype, which supports that transcriptomic phenotypes are determined downstream of the leukemia-initialing event. Overall, our data indicate that treatment response and TKI-efficacy is an unexpected outcome of the differentiation stage at which this leukemia transforms.","abstract":"In BCR-ABL1 lymphoblastic leukemia, treatment heterogeneity to tyrosine kinase inhibitors (TKIs), especially in the absence of kinase domain mutations in BCR-ABL1, is poorly understood. Through deep molecular profiling, we uncovered three transcriptomic subtypes of BCR-ABL1 lymphoblastic leukemia, each representing a maturation arrest at a stage of B-cell progenitor differentiation. An earlier arrest was associated with lineage promiscuity, treatment refractoriness, and poor patient outcomes. A later arrest was associated with lineage fidelity, deep and durable leukemia remissions, and improved patient outcomes. Each maturation arrest was marked by specific genomic events that control different transition points in B-cell development. Interestingly, these events were absent in BCR-ABL1+ pre-leukemic stem cells isolated from patients regardless of subtype, which supports that transcriptomic phenotypes are determined downstream of the leukemia-initialing event. Overall, our data indicate that treatment response and TKI-efficacy is an unexpected outcome of the differentiation stage at which this leukemia transforms.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-13T18:14:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007168","title":"Expression profiles from human naïve B cells infected with EBV or activated with heat-inactivated EBV, respectively.","description":null,"abstract":"Expression profiles from primary naïve B cells from healthy donors. Cells were infected with EBV or activated with heat-inactivated EBV, respectively. RNA samples were isolated at 0, 1, and 4 days post-infection / post-activation. \n\nRNA Samples were isolated at 0 and 2 days post-infection / post-activation.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007169","title":"Machine learning to detect the SINEs of cancer","description":"We previously described an approach called RealSeqS to evaluate aneuploidy in plasma cell-free DNA (cfDNA) through the amplification of ~350,000 repeated elements with a single primer. We hypothesized that an unbiased evaluation of the large amount of sequencing data obtained with RealSeqS might reveal other differences between plasma samples from patients with and without cancer. This hypothesis was tested through the development of a novel machine-learning approach called Alu Profile Learning Using Sequencing (A-PLUS) and its application to samples from 5108 individuals, 2037 with cancer and the remainder without cancer. Samples from cancer patients and controls were pre-specified into four cohorts used for: 1) model training, 2) analyte integration and threshold determination, 3) validation, and 4) reproducibility. A-PLUS alone provided a sensitivity of 40.5% across 11 different cancer types  in the Validation Cohort, at a specificity of 98.5%. Combining A-PLUS with aneuploidy and 8 common protein biomarkers detected 51% of 1167 cancers at 98.9% specificity.  We found that part of the power of A-PLUS could be ascribed to a single feature – the global reduction of AluS sub-family elements in the circulating DNA of cancer patients.  We confirmed this reduction through the analysis of another independent dataset obtained with a very different approach (whole genome sequencing). The evaluation of Alu elements therefore has the potential to enhance the performance of several methods designed for the earlier detection of cancer.","abstract":"We previously described an approach called RealSeqS to evaluate aneuploidy in plasma cell-free DNA (cfDNA) through the amplification of ~350,000 repeated elements with a single primer. We hypothesized that an unbiased evaluation of the large amount of sequencing data obtained with RealSeqS might reveal other differences between plasma samples from patients with and without cancer. This hypothesis was tested through the development of a novel machine-learning approach called Alu Profile Learning Using Sequencing (A-PLUS) and its application to samples from 5108 individuals, 2037 with cancer and the remainder without cancer. Samples from cancer patients and controls were pre-specified into four cohorts used for: 1) model training, 2) analyte integration and threshold determination, 3) validation, and 4) reproducibility. A-PLUS alone provided a sensitivity of 40.5% across 11 different cancer types  in the Validation Cohort, at a specificity of 98.5%. Combining A-PLUS with aneuploidy and 8 common protein biomarkers detected 51% of 1167 cancers at 98.9% specificity.  We found that part of the power of A-PLUS could be ascribed to a single feature – the global reduction of AluS sub-family elements in the circulating DNA of cancer patients.  We confirmed this reduction through the analysis of another independent dataset obtained with a very different approach (whole genome sequencing). The evaluation of Alu elements therefore has the potential to enhance the performance of several methods designed for the earlier detection of cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007170","title":"Convergent evolution drives therapy resistance in DNA repair-deficient mCRPC - WGS","description":null,"abstract":"These are FASTQ files obtained from RNA-sequencing and DNA-sequencing of tumor biopsies obtained from metastatic castration-resistant prostate tumors. Patients were treated with multiple lines of therapy with samples obtained at the time of rapid autopsy following the CASCADE protocol. Multiple biopsies were obtained from each patient under guidance of pathology. DNA were analyzed by high-depth whole genome, exome, and targeted sequencing. RNA were analyzed using a Nugen amplification protocol as described in Quigley Cell 2018.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007171","title":"A Machine Learning Tool Integrating Circulating Cell-Free DNA Methylation with Clinical Variables for Non-Invasive Diagnosis of Liver Graft Pathology","description":"Liver Transplant Recipients (LTRs) with elevated liver enzymes can develop graft injury due to various etiologies, such as T-cell mediated rejection (TCMR) and NASH (NASH-LT). While liver biopsy is the gold standard method for diagnosis of graft pathology, it is invasive and is associated with risks. The goal of our study was to develop a Machine Learning (ML) tool integrating clinical variables with methylation patterns on circulating DNA in plasma as a non-invasive diagnostic tool of graft injury. We generated methylation profiles of circulating DNA in a pilot study of 43 LTRs (11 NASH-LT, 19 TCMR, and 13 Control-LT), and developed an L2 multinomial logistic regression ML approach across 101 bootstrapped models to distinguish between the graft conditions. NASH was associated with distinctive methylation patterns on genes involved in fatty acid metabolism, while methylation of platelet-derived growth factors was identified in patients with TCMR. Our ML model achieved a mean multi-classification accuracy of 0.91, with mean specificity and sensitivity of 0.94 and 0.91, respectively. The model was found to be particularly adept at detecting TCMR and Control-LT, with true positive rates (TPRs) of 95% and 90%, and areas under the curve (AUROC) of 0.992 and 0.985, respectively. For NASH-LT, the models achieved a performance with a TPR of 82% and an AUROC of 0.991. These preliminary results suggest that our newly developed ML tool, leveraging cell-free DNA methylation and clinical variables, is a promising non-invasive classifier of graft pathology.","abstract":"Liver Transplant Recipients (LTRs) with elevated liver enzymes can develop graft injury due to various etiologies, such as T-cell mediated rejection (TCMR) and NASH (NASH-LT). While liver biopsy is the gold standard method for diagnosis of graft pathology, it is invasive and is associated with risks. The goal of our study was to develop a Machine Learning (ML) tool integrating clinical variables with methylation patterns on circulating DNA in plasma as a non-invasive diagnostic tool of graft injury. We generated methylation profiles of circulating DNA in a pilot study of 43 LTRs (11 NASH-LT, 19 TCMR, and 13 Control-LT), and developed an L2 multinomial logistic regression ML approach across 101 bootstrapped models to distinguish between the graft conditions. NASH was associated with distinctive methylation patterns on genes involved in fatty acid metabolism, while methylation of platelet-derived growth factors was identified in patients with TCMR. Our ML model achieved a mean multi-classification accuracy of 0.91, with mean specificity and sensitivity of 0.94 and 0.91, respectively. The model was found to be particularly adept at detecting TCMR and Control-LT, with true positive rates (TPRs) of 95% and 90%, and areas under the curve (AUROC) of 0.992 and 0.985, respectively. For NASH-LT, the models achieved a performance with a TPR of 82% and an AUROC of 0.991. These preliminary results suggest that our newly developed ML tool, leveraging cell-free DNA methylation and clinical variables, is a promising non-invasive classifier of graft pathology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-17T20:30:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007172","title":"Establishment and characterization of an Epstein-Barr virus-positive cell line from a non-keratinizing differentiated primary nasopharyngeal carcinoma","description":"Nasopharyngeal carcinoma (NPC), a cancer that is etiologically associated with the Epstein-Barr virus (EBV), is endemic in Southern China and Southeast Asia. The scarcity of representative NPC cell lines owing to the frequent loss of EBV episomes following prolonged propagation and compromised authenticity of previous models underscores the critical need for new EBV-positive NPC models. Herein, we describe the establishment of a new EBV-positive NPC cell line, designated NPC268 from a primary non-keratinizing, differentiated NPC tissue. NPC268 can undergo productive lytic reactivation of EBV and is highly tumorigenic in immunodeficient mice. Whole-genome sequencing (WGS) revealed close similarities with the tissue of origin, including large chromosomal rearrangements, while whole-genome bisulfite sequencing (WGBS) and RNA sequencing demonstrated a hypomethylated genome and enrichment in immune-related pathways, respectively.","abstract":"Nasopharyngeal carcinoma (NPC), a cancer that is etiologically associated with the Epstein-Barr virus (EBV), is endemic in Southern China and Southeast Asia. The scarcity of representative NPC cell lines owing to the frequent loss of EBV episomes following prolonged propagation and compromised authenticity of previous models underscores the critical need for new EBV-positive NPC models. Herein, we describe the establishment of a new EBV-positive NPC cell line, designated NPC268 from a primary non-keratinizing, differentiated NPC tissue. NPC268 can undergo productive lytic reactivation of EBV and is highly tumorigenic in immunodeficient mice. Whole-genome sequencing (WGS) revealed close similarities with the tissue of origin, including large chromosomal rearrangements, while whole-genome bisulfite sequencing (WGBS) and RNA sequencing demonstrated a hypomethylated genome and enrichment in immune-related pathways, respectively.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-18T08:24:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007173","title":"H3Africa - An integrated approach to the identification of genetic determinants of susceptibility to trypanosomiasis","description":"The over-arching aim of this network is to improve the health of people living in some of the poorest countries in the world that carry a disproportionate burden of infectious diseases. Despite their importance, the study of many tropical diseases has lagged behind that of diseases of developed countries. This network will redress the balance by performing high quality research into two neglected tropical diseases, human African Trypanosomiasis (HAT) and schistosomiasis. Our aim is to investigate the genetic determinants of the human reservoirs of HAT and schistosomiasis, filling an important knowledge gap, while extending and strengthening the underpinning infrastructure to deliver these scientific objectives in particular by developing the next generation of African geneticists.","abstract":"The over-arching aim of this network is to improve the health of people living in some of the poorest countries in the world that carry a disproportionate burden of infectious diseases. Despite their importance, the study of many tropical diseases has lagged behind that of diseases of developed countries. This network will redress the balance by performing high quality research into two neglected tropical diseases, human African Trypanosomiasis (HAT) and schistosomiasis. Our aim is to investigate the genetic determinants of the human reservoirs of HAT and schistosomiasis, filling an important knowledge gap, while extending and strengthening the underpinning infrastructure to deliver these scientific objectives in particular by developing the next generation of African geneticists.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-18T08:52:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007174","title":"Targeted_NanoSeq__Testis_","description":"Targeted NanoSeq in testes from a number of donors, both healthy and with pathology. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across a large number of testes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007175","title":"Exome_NanoSeq__Thyroid_","description":"Exome NanoSeq in thyroid from a number of donors, both healthy and with pathology.","abstract":"Investigating the driver landscape in thyroid, in both health and disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-18T11:35:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007176","title":"Targeted_NanoSeq__Breast_","description":"Targeted NanoSeq in breast tissue from a number of healthy donors. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across a large number of breast specimens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007177","title":"Exome_NanoSeq__Dermal_fibroblasts_","description":"Exome NanoSeq in dermal fibroblasts of healthy patients. These will be obtained through LCM and cell population isolation protocols.","abstract":"Investigating the driver landscape in dermal fibroblasts.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007178","title":"Exome_NanoSeq__Adrenal_","description":"Exome NanoSeq in adrenal glands from a number of donors, both healthy and with pathology.","abstract":"Investigating the driver landscape in adrenals, in both health and disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007179","title":"Targeted_NanoSeq__Lung_","description":"Targeted NanoSeq in testes from a number of donors, both healthy and with pathology. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across a large number of testes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007180","title":"Chip_seq_oesophageal_adenocarcinoma_","description":"There is complex interplay between underlying genetic sequence and epigenetic factors, however this interplay is still illusive. Massively reconstructed cancer genomes can be used in order to better understand this relationship. Six oesophageal adenocarcinoma organoids will be sequenced using long read sequencing technologies and will be profiled for a range of epigenetic marks. Combination of genetic and epigenetic data will allow the thorough characterisation of reference cancer genomes and will provide novel insights into mechanisms of gene regulation.\nDescription:\nChip-seq Sequencing of 5 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical rescetion of the tumour. All model derivations took place with the CGaP facility in Sanger.","abstract":"There is complex interplay between underlying genetic sequence and epigenetic factors, however this interplay is still illusive. Massively reconstructed cancer genomes can be used in order to better understand this relationship. Six oesophageal adenocarcinoma organoids will be sequenced using long read sequencing technologies and will be profiled for a range of epigenetic marks. Combination of genetic and epigenetic data will allow the thorough characterisation of reference cancer genomes and will provide novel insights into mechanisms of gene regulation.\nDescription:\nChip-seq Sequencing of 5 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical rescetion of the tumour. All model derivations took place with the CGaP facility in Sanger.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-18T12:22:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007181","title":"Primary_DIPG_expression_profiles","description":"In this study, we used RNA-sequencing gene expression profiling in order to characterize specific phenotypic traits in DIPG. Seventeen primary tumor samples stereotactically biopsied at diagnosis by neurosurgeons in the Necker-Enfants Malades hospital (Paris, France) and snap-frozen for RNA extraction and subsequent poly-A mRNA purification.","abstract":"In this study, we used RNA-sequencing gene expression profiling in order to characterize specific phenotypic traits in DIPG. Seventeen primary tumor samples stereotactically biopsied at diagnosis by neurosurgeons in the Necker-Enfants Malades hospital (Paris, France) and snap-frozen for RNA extraction and subsequent poly-A mRNA purification.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-18T13:18:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007182","title":"3D-GSC_expression_profiles","description":"In this study, we used RNA-sequencing gene expression profiling in order to characterize specific phenotypic traits in DIPG-derived glioma stem cell (GSC) models. Twenty-two primary GSC models derived from biopsies collected at diagnosis were cultured in an ECM-mimicking compound before for RNA extraction and subsequent rRNA-depletion and sequencing .","abstract":"In this study, we used RNA-sequencing gene expression profiling in order to characterize specific phenotypic traits in DIPG-derived glioma stem cell (GSC) models. Twenty-two primary GSC models derived from biopsies collected at diagnosis were cultured in an ECM-mimicking compound before for RNA extraction and subsequent rRNA-depletion and sequencing .","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-18T13:18:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007183","title":"Targeted_NanoSeq_Liver_GRCh37","description":"Targeted NanoSeq in livers from a number of donors, including donors with no past medical history of liver issues, as well as those with diabetes mellitus, non-alcoholic fatty liver disease, alcoholic liver disease, and cirrhosis of other aetiology. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across a large number of liver specimens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007184","title":"Accuracy and repeatability of epigenome-based signatures trained on Illumina MethylationEPIC BeadChip data","description":"Illumina DNA methylation microarrays are popular tools for discovering methylation patterns that enable epigenome-based trait prediction. To ensure reliable and accurate predictions, the robustness of the methylation assay is critical. This dataset comprises technical quadruplicate llumina MethylationEPIC (v1.0) data from matched cervical and blood samples, derived from four individuals, to evaluate the precision of methylation values and the repeatability of epigenome-based models trained to predict disease and aging. Fresh, and frozen blood were treated as separate tissue types, so the data stems from 4 * 4 * 3 = 48 microarrays.","abstract":"Illumina DNA methylation microarrays are popular tools for discovering methylation patterns that enable epigenome-based trait prediction. To ensure reliable and accurate predictions, the robustness of the methylation assay is critical. This dataset comprises technical quadruplicate llumina MethylationEPIC (v1.0) data from matched cervical and blood samples, derived from four individuals, to evaluate the precision of methylation values and the repeatability of epigenome-based models trained to predict disease and aging. Fresh, and frozen blood were treated as separate tissue types, so the data stems from 4 * 4 * 3 = 48 microarrays.","study_type":"Other","pubmed_ids":[39289706],"external_links":null,"is_released":true,"released_date":"2023-04-18T22:13:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007185","title":"Kings_Hepatoblastoma_Behjati_Nanoseq_Managed_Access_GRCh37","description":"A study of the development of liver based tumours - using 1000Genomes_hs37d5 Ensembl 75 ref.","abstract":"A study of the development of liver based tumours - using 1000Genomes_hs37d5 Ensembl 75 ref.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007186","title":"Structural variant analysis of homologous recombination-deficient genomes","description":"Homologous recombination (HR) deficiency causes DNA breaks and cytogenetic aberrations. Paradoxically, the types of DNA rearrangements specifically associated with HR-deficient cancers only minimally impact chromosomal structure. Addressing this, we combined a genome graph analysis of short-read whole genome sequencing (WGS) profiles across thousands of tumors with deep linked-read (LR) WGS of 46 BRCA1 or BRCA2 mutant breast cancers to discover a distinct class of HR deficiency-enriched rearrangements called reciprocal pairs.  LR WGS showed that reciprocal pairs with identical rearrangement orientations gave rise to one of two distinct chromosomal outcomes, distinguishable only with long molecule data.  While one (cis) outcome corresponded to the copy and pasting of a small segment to a distant site, a second (trans) outcome was a quasi-balanced translocation or multi-megabase inversion with substantial (10kb) duplications at each junction. The full spectrum of reciprocal pair outcomes could be explained by an HR-independent replication restart repair mechanism. LR WGS additionally identified single-strand annealing (SSA) as a BRCA2-deficiency specific repair pathway in human cancers. Replication restart- and SSA-associated SVs improved BRCA1- vs. BRCA2- deficiency classification and identified metastatic cancer cases with favorable chemotherapy responses. Our data reveal classes of BRCA1- and BRCA2-deficiency specific rearrangements as drivers of cytogenetic aberrations in HR deficient cells.","abstract":"Homologous recombination (HR) deficiency causes DNA breaks and cytogenetic aberrations. Paradoxically, the types of DNA rearrangements specifically associated with HR-deficient cancers only minimally impact chromosomal structure. Addressing this, we combined a genome graph analysis of short-read whole genome sequencing (WGS) profiles across thousands of tumors with deep linked-read (LR) WGS of 46 BRCA1 or BRCA2 mutant breast cancers to discover a distinct class of HR deficiency-enriched rearrangements called reciprocal pairs.  LR WGS showed that reciprocal pairs with identical rearrangement orientations gave rise to one of two distinct chromosomal outcomes, distinguishable only with long molecule data.  While one (cis) outcome corresponded to the copy and pasting of a small segment to a distant site, a second (trans) outcome was a quasi-balanced translocation or multi-megabase inversion with substantial (10kb) duplications at each junction. The full spectrum of reciprocal pair outcomes could be explained by an HR-independent replication restart repair mechanism. LR WGS additionally identified single-strand annealing (SSA) as a BRCA2-deficiency specific repair pathway in human cancers. Replication restart- and SSA-associated SVs improved BRCA1- vs. BRCA2- deficiency classification and identified metastatic cancer cases with favorable chemotherapy responses. Our data reveal classes of BRCA1- and BRCA2-deficiency specific rearrangements as drivers of cytogenetic aberrations in HR deficient cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-20T02:25:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007187","title":"RNA sequencing of primary B-cells infected with EBV virus","description":null,"abstract":"Expression profiles from primary naïve B cells from healthy donors. Cells were infected with EBV or activated with heat-inactivated EBV, respectively. Additionally cells were treated with 5ng/ml CpG or a BCR-crosslinking mixture in presence or absence of 10µM Linrodostat (IDO1 inhibitor). RNA samples were isolated at 0, 1, 2 and 4 days post-infection / post-activation.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-04-16T10:05:53.77495+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007188","title":"Transposable elements are co-opted as oncogenic regulatory elements by lineage-specific transcription factors in prostate cancer","description":null,"abstract":"Transposable elements hold regulatory functions that impact cell fate determination by controlling gene expression, which when altered can promote oncogenesis 1,2. Despite accounting for half of the human genome 3, little is known about the transcriptional mechanisms that confer regulatory properties to transposable elements in pluripotent, and mature versus oncogenic cell states. Through positional analysis over repetitive DNA sequences of H3K27ac ChIP-seq data from 32 different normal cell and tissue states, we report pluripotent stem and mature cell states-specific “regulatory transposable elements”. Those specific to pluripotent stem cells are binding sites for the pluripotency factors NANOG, SOX2 and OCT4. In mature cell and tissue states, regulatory transposable elements are docking sites for lineage-specific transcription factors, such as AR and FOXA1 in benign prostate epithelium. Expanding the positional analysis to localized prostate tumors, we show how cancer cell states dependent on AR share regulatory transposable elements with pluripotent stem cells. Using CRISPRi genome hacking technology, we demonstrate the requirement for regulatory Tigger3a transposable elements for the growth of AR-dependent prostate cancer. Together, our results suggest that oncogenesis arises in part from hijacking transposable elements into regulatory elements for lineage-specific transcription factors.\nStatement of significance\nWe show that oncogenesis relies on co-opting transposable elements from pluripotent stem cells as regulatory elements altering the recruitment of lineage specific transcription factors. We further discover how co-option is dependent on active chromatin states with important implications for developing treatment options against cancer drivers in the repetitive DNA.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-20T15:07:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007189","title":"HGSOC organoid sequencing study","description":null,"abstract":"High-grade serous ovarian carcinoma (HGSOC) is the most genomically complex cancer, characterized by ubiquitous TP53 mutation, profound chromosomal instability and heterogeneity. The mutational processes driving chromosomal instability in HGSOC can be distinguished by specific copy number signatures. To develop clinically relevant models of these mutational processes we derived 15 continuous HGSOC patient-derived organoids (PDOs) and characterized them using bulk transcriptomic, bulk genomic, single cell genomic, and drug sensitivity assays. We show that HGSOC PDOs comprise communities of different clonal populations and represent models of different causes of chromosomal instability including homologous recombination deficiency, chromothripsis, tandem-duplicator phenotype and whole genome duplication. We also show that these PDOs can be used as exploratory tools to study transcriptional effects of copy number alterations as well as compound-sensitivity tests. In summary, HGSOC PDO cultures provide validated genomic models for studies of specific mutational processes and precision therapeutics.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-20T16:45:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007190","title":"Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO)","description":null,"abstract":"154 patients received lapatinib, 149 trastuzumab, and 152 the combination. pCR rate was significantly higher in the group given lapatinib and trastuzumab (78 of 152 patients [51·3%; 95% CI 43·1-59·5]) than in the group given trastuzumab alone (44 of 149 patients [29·5%; 22·4-37·5]; difference 21·1%, 9·1-34·2, p=0·0001). We recorded no significant difference in pCR between the lapatinib (38 of 154 patients [24·7%, 18·1-32·3]) and the trastuzumab (difference -4·8%, -17·6 to 8·2, p=0·34) groups. No major cardiac dysfunctions occurred. Frequency of grade 3 diarrhoea was higher with lapatinib (36 patients [23·4%]) and lapatinib plus trastuzumab (32 [21·1%]) than with trastuzumab (three [2·0%]). Similarly, grade 3 liver-enzyme alterations were more frequent with lapatinib (27 [17·5%]) and lapatinib plus trastuzumab (15 [9·9%]) than with trastuzumab (11 [7·4%]).","study_type":"RNASeq","pubmed_ids":[22257673,27684533,31377477],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007191","title":"Accessibility Over Transposable Elements Reveals Genetic Determinants of Stemness Properties in Normal and Leukemic Hematopoiesis","description":null,"abstract":"Despite most acute myeloid leukemia (AML) patients achieving complete remission after induction chemotherapy, two thirds of patients will relapse with fatal disease within 5 years. AML is organized as a cellular hierarchy sustained by leukemia stem cells (LSC) at the apex, with LSC properties directly linked to tumor progression, therapy failure and disease relapse 1–3. Despite the central role of LSC in poor patient outcomes, little is known of the genetic determinants of their stemness properties 4–6. Although much AML research focuses on mutational processes and their impact on gene expression programs, the genetic determinants of cell state properties including stemness expand beyond mutations, relying on the genetic architecture captured in the chromatin of each cell 7–9. As LSCs share many functional and molecular properties with normal hematopoietic stem cells (HSC), we identified genetic determinants of primitive populations enriched for LSCs and HSCs in comparison with their downstream mature progeny by investigating their chromatin accessibility. Our work reveals how distinct transposable element (TE) subfamilies are used in primitive versus mature populations, functioning as docking sites for stem cell-associated regulators of genome topology or lineage-specific transcription regulators in primitive and mature populations, respectively. We further show how TE subfamilies accessible in LSCs define docking sites for several oncogenic drivers in AML, including LYL1. Using chromatin accessibility profiles from a cohort of AML patients, we further show the clinical utility of our TE accessibility-based LSCTE121 scoring scheme to identify patients with high rates of relapse. Collectively, our work reveals how different accessible TE subfamilies serve as genetic determinants of stemness properties in normal and leukemic hematopoietic stem cells.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-21T17:15:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007192","title":"Enhanced detection of MRD with cfDNA Fragmentomics.","description":null,"abstract":"The circulating tumor DNA (ctDNA) mutation-based approach shows limited performance in minimal residual disease (MRD) detection, especially for landmark MRD detection at an early-stage cancer after surgery. Here, we describe a cell-free DNA (cfDNA) fragmentomics-based method in MRD detection of resectable non-small cell lung cancer using whole genome sequencing, and the cfDNA-fragmentomics showed a great sensitivity in predicting prognosis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-23T15:07:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007193","title":"Human resident liver myeloid cells protect against metabolic stress in obesity","description":null,"abstract":"Independent of their inflammatory phenotype, macrophages are key orchestrators of hepatic metabolism. Non-alcoholic fatty liver disease (NAFLD) often occurs in obese individuals and is among the most common causes of cirrhosis, the terminal chronic liver disease that may necessitate liver transplantation. While multiple populations of macrophages have been described in the human liver, their function and turnover in obese patients at high risk of developing NAFLD and cirrhosis is currently unknown. Herein we identified a specific human population of resident liver myeloid cells that protects against the metabolic impairment associated with obesity. By studying the turnover of liver myeloid cells in individuals undergoing liver transplantation using markers of donor-recipient mismatch, we made the novel discovery that liver myeloid cell turnover differs between humans and mice. Using single cell techniques and flow cytometry we determined that the proportion of the protective resident liver myeloid cells, denoted liver myeloid cells 2 (LM2), decreases during obesity. Functional validation approaches using human 2D and 3D cultures revealed that the presence of LM2 ameliorates the oxidative stress associated with obese conditions. Our study indicates that resident myeloid cells could be a therapeutic target to decrease the oxidative stress associated with NAFLD.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007194","title":"Human liver NPCs single cell project","description":"Independent of their inflammatory phenotype, macrophages are key orchestrators of hepatic metabolism. Non-alcoholic fatty liver disease (NAFLD) often occurs in obese individuals and is among the most common causes of cirrhosis, the terminal chronic liver disease that may necessitate liver transplantation. While multiple populations of macrophages have been described in the human liver, their function and turnover in obese patients at high risk of developing NAFLD and cirrhosis is currently unknown. Herein we identified a specific human population of resident liver myeloid cells that protects against the metabolic impairment associated with obesity. By studying the turnover of liver myeloid cells in individuals undergoing liver transplantation using markers of donor-recipient mismatch, we made the novel discovery that liver myeloid cell turnover differs between humans and mice. Using single cell techniques and flow cytometry we determined that the proportion of the protective resident liver myeloid cells, denoted liver myeloid cells 2 (LM2), decreases during obesity. Functional validation approaches using human 2D and 3D cultures revealed that the presence of LM2 ameliorates the oxidative stress associated with obese conditions. Our study indicates that resident myeloid cells could be a therapeutic target to decrease the oxidative stress associated with NAFLD.","abstract":"Independent of their inflammatory phenotype, macrophages are key orchestrators of hepatic metabolism. Non-alcoholic fatty liver disease (NAFLD) often occurs in obese individuals and is among the most common causes of cirrhosis, the terminal chronic liver disease that may necessitate liver transplantation. While multiple populations of macrophages have been described in the human liver, their function and turnover in obese patients at high risk of developing NAFLD and cirrhosis is currently unknown. Herein we identified a specific human population of resident liver myeloid cells that protects against the metabolic impairment associated with obesity. By studying the turnover of liver myeloid cells in individuals undergoing liver transplantation using markers of donor-recipient mismatch, we made the novel discovery that liver myeloid cell turnover differs between humans and mice. Using single cell techniques and flow cytometry we determined that the proportion of the protective resident liver myeloid cells, denoted liver myeloid cells 2 (LM2), decreases during obesity. Functional validation approaches using human 2D and 3D cultures revealed that the presence of LM2 ameliorates the oxidative stress associated with obese conditions. Our study indicates that resident myeloid cells could be a therapeutic target to decrease the oxidative stress associated with NAFLD.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-23T22:45:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007195","title":"Developing somatic copy number and mutation calling tools for a bespoke sequencing platform","description":"We previously developed a linked-read sequencing platform (DigiPico) for analysing whole cancer genomes from picogram quantities of tumour DNA. The aim of this study was to develop and evaluate the specialised computational approaches required to obtain clinically useful results from the raw data. To this end, we performed matched DigiPico, bulk tumour and germline WGS on samples from four patients.","abstract":"We previously developed a linked-read sequencing platform (DigiPico) for analysing whole cancer genomes from picogram quantities of tumour DNA. The aim of this study was to develop and evaluate the specialised computational approaches required to obtain clinically useful results from the raw data. To this end, we performed matched DigiPico, bulk tumour and germline WGS on samples from four patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-24T10:37:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007196","title":"Genomic landscape of normal and breast cancer tissues in a Hungarian pilot cohort","description":null,"abstract":"We performed whole-genome sequencing of two Hungarian breast cancer cohorts by using WGS and the Illumina TruSight Oncology 500 assay and we compared our results with that observed in various European populations. \nWe have characterized (i) the most frequently mutated canonical cancer-related genes in the germline genomes of Hungarian patients with breast cancer; (ii) we explored genes most commonly affected by somatic mutations and (iii) we have analyzed the copy-number alterations and somatic mutational landscape","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007197","title":"Monocyte Spike-in RNASeq","description":"Please see our related publication, 'Tumor monocyte content predicts immunochemotherapy outcomes in esophageal adenocarcinoma'.","abstract":"Please see our related publication, 'Tumor monocyte content predicts immunochemotherapy outcomes in esophageal adenocarcinoma'.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-24T15:37:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007198","title":"Single-cell analysis reveals transcriptomic and epigenomic impacts on the maternal-fetal interface upon SARS-CoV-2 infection","description":null,"abstract":"During pregnancy, the maternal-fetal interface plays vital roles in fetal development. Its disruption is frequently found in pregnancy complications. Recent works show increased incidences of adverse pregnancy outcomes in COVID-19 patients; however, the mechanism remains unclear. Here, we analyzed the molecular impacts of SARS-CoV-2 infection on the maternal-fetal interface. Generating bulk and single-nucleus transcriptomic and epigenomic profiles from COVID-19 patients and control samples, we discovered aberrant immune activation and angiogenesis patterns in distinct cells from patients. Surprisingly, retrotransposons were also dysregulated in specific cell types. Notably, reduced enhancer activities of LTR8B elements were functionally linked to the downregulation of Pregnancy-Specific Glycoprotein genes in syncytiotrophoblasts. Our findings revealed that SARS-CoV-2 infection induced significant changes to the epigenome and transcriptome at the maternal-fetal interface, which may be associated with pregnancy complications.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007199","title":"Targeted_NanoSeq_Liver_LiverPanelV1","description":"Targeted NanoSeq in livers from a number of donors, including donors with no past medical history of liver issues, as well as those with diabetes mellitus, non-alcoholic fatty liver disease, alcoholic liver disease, and cirrhosis of other aetiology. A custom-designed liver panel will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across a large number of liver specimens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007200","title":"The genetic history of the southern Andes from present-day Mapuche ancestry","description":"We generate genome-wide data from 64 participants from three Mapuche populations in Southern Chile: Pehuenche, Lafkenche, and Huilliche. Broadly, we describe three main ancestry blocks with a common origin, which characterize the Southern Cone, the Central Andes, and Amazonia. Within the Southern Cone, ancestors of the Mapuche lineages differentiated from those of the Far South during the Middle Holocene, and did not experience further migration waves from the north. We find that the deep genetic split between the Central and Southern Andes is followed by instances of gene flow, which may have accompanied the southward spread of cultural traits from the Central Andes, including crops and loanwords from Quechua into Mapudungun (the language of the Mapuche). Our findings add new perspectives on the genetic (pre)history of South America, from first settlement through to the present-day indigenous presence. Follow-up fieldwork took these results back to the indigenous communities to contextualize the genetic narrative alongside indigenous knowledge and perspectives.","abstract":"We generate genome-wide data from 64 participants from three Mapuche populations in Southern Chile: Pehuenche, Lafkenche, and Huilliche. Broadly, we describe three main ancestry blocks with a common origin, which characterize the Southern Cone, the Central Andes, and Amazonia. Within the Southern Cone, ancestors of the Mapuche lineages differentiated from those of the Far South during the Middle Holocene, and did not experience further migration waves from the north. We find that the deep genetic split between the Central and Southern Andes is followed by instances of gene flow, which may have accompanied the southward spread of cultural traits from the Central Andes, including crops and loanwords from Quechua into Mapudungun (the language of the Mapuche). Our findings add new perspectives on the genetic (pre)history of South America, from first settlement through to the present-day indigenous presence. Follow-up fieldwork took these results back to the indigenous communities to contextualize the genetic narrative alongside indigenous knowledge and perspectives.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-26T12:56:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007201","title":"Methylation profiles in patients with blastic plasmacytoid dendritic cell neoplasm","description":"We added 7 additional samples to our previous cohort (EGAS00001006166). Each samples comprises RNA-seq and whole exome sequencing data. Methylation EPIC Array data have been deposited in Gene Expression Omnibus (GEO) under accession number GSE230487.","abstract":"We added 7 additional samples to our previous cohort (EGAS00001006166). Each samples comprises RNA-seq and whole exome sequencing data. Methylation EPIC Array data have been deposited in Gene Expression Omnibus (GEO) under accession number GSE230487.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-27T08:21:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007202","title":"Targeted_EMSeq___Development","description":"Development of a targeted methylation assay to determine the cell-type composition of a sample.","abstract":"Development of a targeted methylation assay to determine the cell-type composition of a sample","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-04-27T16:29:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007203","title":"SARS-CoV-2, SARS-CoV, MERS-CoV and HCoV-229E-infected human airway epithelial cell cultures","description":null,"abstract":"Here, we analyzed the transcriptome of primary human bronchial epithelial cells (PBEC), differentiated at the air-liquid interface (ALI) after infection with equal plaque forming units (PFUs) of SARS-CoV-2, SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV) and HCoV-229E using bulk RNA sequencing (RNA-seq) at 24, 48 and 72 hours post infection (n=5).","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007204","title":"Bacterial SNPs in the human gut microbiome associate with host BMI","description":"Genome-wide association studies (GWAS) have revolutionized the field of genetics, providing numerous associations between human SNPs and health traits. Likewise, metagenome-wide association studies (MWAS) between bacterial SNPs and human traits can suggest mechanistic links between the microbiota and its host. However, very few such studies have been done to date, in part due to the large number of samples required to address the variable coverage of bacteria across samples and the fact that most bacteria are present in only a subset of the population. Here, we devised an MWAS framework to detect SNPs and associate them with host phenotypes systematically. We recruited and obtained gut metagenomic samples from a cohort of 7,190 healthy individuals and discovered 1,358 statistically significant associations between a bacterial SNP and host body mass index (BMI). To address the possible effects of population structure and linkage disequilibrium, we applied a clumping procedure, and found 40 independent associations between SNPs and host BMI. We uncovered BMI-associated SNPs in the genomes of 27 bacterial species, even though the relative abundance of 12 of these species was not associated with the phenotype. We separated genome-wide sub-species variations from local associations in individual SNPs, and demonstrated how this framework can highlight specific bacterial functions of interest. Our results demonstrate the importance of considering nucleotide-level diversity in microbiome studies and pave the way toward a better understanding of interpersonal gut microbiome differences and their health implications.","abstract":"Genome-wide association studies (GWAS) have revolutionized the field of genetics, providing numerous associations between human SNPs and health traits. Likewise, metagenome-wide association studies (MWAS) between bacterial SNPs and human traits can suggest mechanistic links between the microbiota and its host. However, very few such studies have been done to date, in part due to the large number of samples required to address the variable coverage of bacteria across samples and the fact that most bacteria are present in only a subset of the population. Here, we devised an MWAS framework to detect SNPs and associate them with host phenotypes systematically. We recruited and obtained gut metagenomic samples from a cohort of 7,190 healthy individuals and discovered 1,358 statistically significant associations between a bacterial SNP and host body mass index (BMI). To address the possible effects of population structure and linkage disequilibrium, we applied a clumping procedure, and found 40 independent associations between SNPs and host BMI. We uncovered BMI-associated SNPs in the genomes of 27 bacterial species, even though the relative abundance of 12 of these species was not associated with the phenotype. We separated genome-wide sub-species variations from local associations in individual SNPs, and demonstrated how this framework can highlight specific bacterial functions of interest. Our results demonstrate the importance of considering nucleotide-level diversity in microbiome studies and pave the way toward a better understanding of interpersonal gut microbiome differences and their health implications.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-04T09:33:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007205","title":"RNA-Sequencing data of patient derived normal fibroblasts (NFs), cancer associated fibroblasts (CAFs) and tumor spheroid samples","description":"RNA-Sequencing data of patient derived normal fibroblasts (NFs), cancer associated fibroblasts (CAFs) and tumor spheroid samples performed in the context of the characterization of an IL1R1 positive CAF population in CRC tumour samples.","abstract":"RNA-Sequencing data of patient derived normal fibroblasts (NFs), cancer associated fibroblasts (CAFs) and tumor spheroid samples performed in the context of the characterization of an IL1R1 positive CAF population in CRC tumour samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-04T14:02:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007206","title":"Whole_genome_sequencing_for_understanding_the_T_cell_response_to_biological_therapeutics","description":"This whole genome sequencing will be performed to accompany the experiments undertaken in the study: HG_Understanding the T cell response to biological therapeutic. In this study, three donors have been treated in a co-culture of T cells and macrophages in the presence or absence of anti-TNF-alpha. Single cell RNA sequencing has been performed and data will be analysed. As these samples have been pooled, whole genome sequencing will be undertaken in order to deconvolute samples and work out each of the donors and conditions.","abstract":"This whole genome sequencing will be performed to accompany the experiments undertaken in the study: HG_Understanding the T cell response to biological therapeutic. In this study, three donors have been treated in a co-culture of T cells and macrophages in the presence or absence of anti-TNF-alpha. Single cell RNA sequencing has been performed and data will be analysed. As these samples have been pooled, whole genome sequencing will be undertaken in order to deconvolute samples and work out each of the donors and conditions.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007207","title":"scRNA-seq analysis Identifies Hepatic IL-13-Producing ILC3-Like Cells Potentially Linked to Liver Fibrosis","description":null,"abstract":"This study investigates the role of intrahepatic innate lymphoid cells (ILCs) in chronic liver disease by characterizing these cells in both healthy and fibrotic livers. Using flow cytometry and single-cell RNA sequencing, we analyzed 50 livers and compared them with colon, tonsil tissue, and peripheral blood to study ILC differentiation, plasticity, and cytokine effects on primary human HSteCs. We discovered a predominant, unconventional IL-13-producing ILC3-like cell, specifically enriched in human liver and more prevalent in fibrotic livers. The ILC3-derived IL-13 induced proinflammatory gene upregulation in HSteCs, implicating a potential role in hepatic fibrogenesis. Additionally, we identified KLRG1-expressing ILC precursors as potential progenitors of these hepatic IL-13+ ILC3-like cells.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-05T12:19:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007208","title":"Blood_single_cell_colony_mutational_and_clonal_landscape","description":"This work aims at investigating the functional impact on cell fitness and clonal dynamics of pathogenic mutations in normal tissues as well as their role in driving cancer initiation. Low input WGS will be performed on blood sample of patients with an inherited cancer predisposition syndrome and used to investigate the mutational and clonal landscape in healthy and cancer tissues.","abstract":"Recent studies have revealed that healthy tissues can harbour cancer driven mutations. However how those mutations induce clonal expansion and how they impact tissue maintenance, ageing and transformation to cancer still requires further investigation.\nThis study aims at identifying cancer driver mutations in normal a cancer tissues of patients with an hereditary cancer syndromes and their role in clonal expiation.\nHematopoietic and progenitor cells will be collected from patient blood samples. Single HSPC will allow to growth in vitro and form a single cell colony. Colony will be then processed for Low input whole genome sequencing.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007209","title":"FGFR-driven urothelial cancer","description":null,"abstract":"We performed a global mutational landscape analysis using tumor samples from the 47 urothelial cancer patients included in MATCH-R or MOSCATO studies, with advanced metastatic disease and WES available (RNAseq is included for 38 patient samples). The most frequently altered genes were TP53 (51%), FGFR3 (34%), and KMT2D (34%).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007210","title":"Clinical Activity of Combined Telomerase Vaccination and Pembrolizumab in Advanced Melanoma: Results from a Phase I Trial","description":"Thirty patients with advanced melanoma were recruited to a clinical trial investigating the therapeutic cancer vaccine, UV1, in combination with pembrolizumab. Whole exome sequencing was performed on melanoma biopsies to determine tumor mutational burden and association with response to therapy. RNA sequencing of matched tumor biopsies to evaluate gene expression profiles at baseline and post-treatment.","abstract":"Thirty patients with advanced melanoma were recruited to a clinical trial investigating the therapeutic cancer vaccine, UV1, in combination with pembrolizumab. Whole exome sequencing was performed on melanoma biopsies to determine tumor mutational burden and association with response to therapy. RNA sequencing of matched tumor biopsies to evaluate gene expression profiles at baseline and post-treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-05T20:10:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007211","title":"WGS","description":"Whole-genome sequencing of pancreatic cancer organoids and matched germline controls.","abstract":"Whole-genome sequencing of pancreatic cancer organoids and matched germline controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-06T05:59:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007212","title":"RNAseq","description":"RNAseq of pancreatic cancer organoids.","abstract":"RNAseq of pancreatic cancer organoids.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-06T05:59:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007213","title":"deep-learning-powered tissue deconvolution for cfDNA","description":"Plasma cell-free DNA (cfDNA) is a noninvasive biomarker for cell death of all organs. Deciphering the tissue origin of cfDNA can reveal abnormal cell death because of diseases, which has great clinical potential in disease detection and monitoring. Despite the great promise, the sensitive and accurate quantification of tissue-derived cfDNA remains challenging to existing methods due to the limited characterization of tissue methylation and the reliance on unsupervised methods. To fully exploit the clinical potential of tissue-derived cfDNA, here we present one of the largest comprehensive and high-resolution methylation atlas based on 521 noncancer tissue samples spanning 29 major types of human tissues. We systematically identified fragment-level tissue-specific methylation patterns and extensively validated them in orthogonal datasets. Based on the rich tissue methylation atlas, we develop the first supervised tissue deconvolution approach, a deep-learning-powered model, cfSort, for sensitive and accurate tissue deconvolution in cfDNA. On the benchmarking data, cfSort showed superior sensitivity and accuracy compared to the existing methods. We further demonstrated the clinical utilities of cfSort with two potential applications: aiding disease diagnosis and monitoring treatment side effects. The tissue-derived cfDNA fraction estimated from cfSort reflected the clinical outcomes of the patients. In summary, the tissue methylation atlas and cfSort enhanced the performance of tissue deconvolution in cfDNA, thus facilitating cfDNA-based disease detection and longitudinal treatment monitoring.","abstract":"Plasma cell-free DNA (cfDNA) is a noninvasive biomarker for cell death of all organs. Deciphering the tissue origin of cfDNA can reveal abnormal cell death because of diseases, which has great clinical potential in disease detection and monitoring. Despite the great promise, the sensitive and accurate quantification of tissue-derived cfDNA remains challenging to existing methods due to the limited characterization of tissue methylation and the reliance on unsupervised methods. To fully exploit the clinical potential of tissue-derived cfDNA, here we present one of the largest comprehensive and high-resolution methylation atlas based on 521 noncancer tissue samples spanning 29 major types of human tissues. We systematically identified fragment-level tissue-specific methylation patterns and extensively validated them in orthogonal datasets. Based on the rich tissue methylation atlas, we develop the first supervised tissue deconvolution approach, a deep-learning-powered model, cfSort, for sensitive and accurate tissue deconvolution in cfDNA. On the benchmarking data, cfSort showed superior sensitivity and accuracy compared to the existing methods. We further demonstrated the clinical utilities of cfSort with two potential applications: aiding disease diagnosis and monitoring treatment side effects. The tissue-derived cfDNA fraction estimated from cfSort reflected the clinical outcomes of the patients. In summary, the tissue methylation atlas and cfSort enhanced the performance of tissue deconvolution in cfDNA, thus facilitating cfDNA-based disease detection and longitudinal treatment monitoring.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-07T01:18:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007214","title":"Genome-wide sequencing of (cell-free) DNA from Nipple aspirate fluid of Breast cancer patients","description":null,"abstract":"Levels of circulating tumor DNA (ctDNA) in liquid biopsies may serve as a sensitive biomarker for real-time, minimally-invasive tumor diagnostics and monitoring. Nipple aspirate fluid (NAF) is a bodily fluid that can be obtained non-invasively with little discomfort through nipple aspiration. Due to its proximity to the breast, NAF contains many biomarkers that can be used for breast cancer detection and treatment monitoring. It may also be a new source for cell-free DNA (cfDNA). We used Illumina Novaseq sequencing and CyclomicsSeq to sequence cell-free DNA in plasma and nipple aspirate fluid of breast cancer patients.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-08T12:32:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007215","title":"EPI-Dx: Epidemiological Investigation of Peptide Signatures, Immunity, Genetic Predisposition, and Changes in SARS-CoV-2","description":null,"abstract":"The consortium of the EPI-Dx project consists of ATLAS Biolabs, in.vent Diagnostica and MicroDiscovery and is funded by the German Federal Ministry of Education and Research, BMBF. The recruitment of 500 patients and provision of specimen material for this study was carried out by in.vent Diagnostica. The laboratory analysis at ATLAS Biolabs includes (i) pre-processing and preparation of the samples, including DNA extraction from blood and RNA extraction from corresponding smear material (ii) molecular genetic analysis using next-generation sequencing (NGS) and microarray technologies and (iii) a first bioinformatics analysis and evaluation of the genetic data. The analysis of biomarkers is carried out by MicroDiscovery. The overall goal of the project is to identify candidates for a diagnostic panel that will enable individualised predictions of potential disease progression and enhance health care response strategies.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007216","title":"TB-DAR Genotyping Study","description":"Active TB patients (sputum smear-positive and GeneXpert-positive) recruited at the Temeke District Hospital in Dar es Salaam, Tanzania, as part of a prospective study that ran between November 2013 and June 2022 (TB-DAR cohort).","abstract":"Active TB patients (sputum smear-positive and GeneXpert-positive) recruited at the Temeke District Hospital in Dar es Salaam, Tanzania, as part of a prospective study that ran between November 2013 and June 2022 (TB-DAR cohort).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-08T15:48:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007217","title":"Transcriptome analyses of a large cohort of adult B cell acute lymphoblastic leukemia samples","description":null,"abstract":"High-risk-relapsed/refractory adult Philadelphia-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL) is a great challenge due to limited possibilities to achieve and maintain a complete response. This also applies to cases with extramedullary (EM) involvement that have poor outcome and no accepted standard therapeutic approaches. The incidence of EM localization in relapsed/refractory B-ALL is poorly investigated: data on patients treated with blinatunomab reported a 40% rate. Some responses were reported in EM relapsed/refractory B-ALL by inotuzumab ozogamicin or CAR-T treatments. However molecular mechanisms of response or refractoriness are usually investigated neither at medullary nor at EM sites. In the complex scenario of pluri-relapsed/refractory B-ALL patients, new target therapies are needed.\nOur analysis started from the case of an adult pluri-relapsed Ph B-ALL patient, poorly sensitive to inotuzumab ozogamicin, DLI and blinatumomab in EM disease, who achieved a durable/complete response after treatment with the BCL2-inhibitor venetoclax. The molecular characterization of medullary and EM samples revealed a tyrosine kinase domain JAK1 mutation in bone marrow and EM samples at relapse. By comparing the expression level of BCL2- and JAK/STAT pathway-related genes between the patient samples, 136 adult JAK1wt B-ALL and 15 healthy controls, we identified differentially expressed genes, including LIFR, MTOR, SHigh-risk-relapsed/refractory adult Philadelphia-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL) is a great challenge due to limited possibilities to achieve and maintain a complete response. This also applies to cases with extramedullary (EM) involvement that have poor outcome and no accepted standard therapeutic approaches. The incidence of EM localization in relapsed/refractory B-ALL is poorly investigated: data on patients treated with blinatunomab reported a 40% rate. Some responses were reported in EM relapsed/refractory B-ALL by inotuzumab ozogamicin or CAR-T treatments. However molecular mechanisms of response or refractoriness are usually investigated neither at medullary nor at EM sites. In the complex scenario of pluri-relapsed/refractory B-ALL patients, new target therapies are needed.\nOur analysis started from the case of an adult pluri-relapsed Ph B-ALL patient, poorly sensitive to inotuzumab ozogamicin, DLI and blinatumomab in EM disease, who achieved a durable/complete response after treatment with the BCL2-inhibitor venetoclax. The molecular characterization of medullary and EM samples revealed a tyrosine kinase domain JAK1 mutation in bone marrow and EM samples at relapse. By comparing the expression level of BCL2- and JAK/STAT pathway-related genes between the patient samples, 136 adult JAK1wt B-ALL and 15 healthy controls, we identified differentially expressed genes, including LIFR, MTOR, SOCS1/2, BCL2/BCL2L1 that are variably modulated at the diverse time-points and might explain the prolonged response to venetoclax (particularly in the EM site, which was partially affected by previous therapies). \nOur results suggest that the deep molecular characterization of both medullary and EM samples is fundamental to identify effective and personalized targeted therapies.OCS1/2, BCL2/BCL2L1 that are variably modulated at the diverse time-points and might explain the prolonged response to venetoclax (particularly in the EM site, which was partially affected by previous therapies). \nOur results suggest that the deep molecular characterization of both medullary and EM samples is fundamental to identify effective and personalized targeted therapies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-08T16:14:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007218","title":"Genomics_of_acral_lentiginous_melanoma_WGS","description":"Melanoma is the most aggressive type of skin cancer, causing about 75% of dermatological cancer deaths. Acral lentiginous melanoma (ALM) is the most common subtype of melanoma in admixed Latin American populations, but very few tumour genomes and exomes, all from European-descent individuals, have been analysed across several studies. Because of this, the genomic landscape of ALM is mostly unknown. Our aim in this project is to define this landscape and identify driver somatic alterations by whole-genome sequencing.","abstract":"Melanoma is the most aggressive type of skin cancer, causing about 75% of dermatological cancer deaths. Acral lentiginous melanoma (ALM) is the most common subtype of melanoma in admixed Latin American populations, but very few tumour genomes and exomes, all from European-descent individuals, have been analysed across several studies. Because of this, the genomic landscape of ALM is mostly unknown. Our aim in this project is to define this landscape and identify driver somatic alterations by whole-genome sequencing.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007219","title":"Digital tEchnology For Lung Cancer Treatment","description":"The aim of the DEFLeCT project (Digital tEchnology For Lung Cancer Treatment) is to generate a technological platform for precision medicine in order to set predictive personalised algorithms for patient diagnosis and therapy. All resectable patients having histologically confirmed stage IB-IIIA non-small cell lung cancer(NSCLC) will be enrolled in the PROMOLE study, a related and ongoing observational prospective clinical study, for tissue sampling. A large biobank of lung cancer samples and the corresponding healthy tissues and biological components (ie, blood, stools, etc.) with complete clinical, pathological and molecular information will be collected. The project will lay the basis of a knowledge hub and qualified technology aimed not only at answering the medical and scientific community's questions, but also meant to be useful to individual patients by predicting the response to adjuvant and second-line drugs in case of relapse of the disease.","abstract":"The aim of the DEFLeCT project (Digital tEchnology For Lung Cancer Treatment) is to generate a technological platform for precision medicine in order to set predictive personalised algorithms for patient diagnosis and therapy. All resectable patients having histologically confirmed stage IB-IIIA non-small cell lung cancer(NSCLC) will be enrolled in the PROMOLE study, a related and ongoing observational prospective clinical study, for tissue sampling. A large biobank of lung cancer samples and the corresponding healthy tissues and biological components (ie, blood, stools, etc.) with complete clinical, pathological and molecular information will be collected. The project will lay the basis of a knowledge hub and qualified technology aimed not only at answering the medical and scientific community's questions, but also meant to be useful to individual patients by predicting the response to adjuvant and second-line drugs in case of relapse of the disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-09T17:39:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007220","title":"Origination of Ovarian Cancer is Dependent on Specific Aneuploidy Landscape","description":"Ovarian high-grade serous carcinoma (HGSC), a highly chromosomally instable malignancy, develops through sequential stages of precursors in fallopian tubes including histologically unremarkable but TP53 mutated clones (p53 signature) and serous tubal intraepithelial carcinoma (STIC). Here, we applied RealSeqS to assess aneuploidy in 127 microdissected tubal regions. We found nearly all p53 signatures lost the entire Chr17 chromosome, offering a “two-hit” mechanism of both TP53 and BRCA1 in BRCA1 germline mutation carriers. Proliferatively active STICs harbor gains of 19q12 (CCNE1), 19q13.2, 8q24 (MYCyc), or 8q arm, while proliferatively dormant STICs show 22q loss. Based on aneuploidy patterns in a training set (n= 67), we developed an algorithm, REAL-FAST, to classify NFTE and STICs into 5 clusters. In an independent validation set (n= 72), REAL-FAST was able to detect STIC/HGSC with high sensitivity and specificity. Taken together, REAL-FAST promises a molecular test for diagnosing HGSC precursor lesions based on specific aneuploidy patterns.","abstract":"Ovarian high-grade serous carcinoma (HGSC), a highly chromosomally instable malignancy, develops through sequential stages of precursors in fallopian tubes including histologically\nunremarkable but TP53 mutated clones (p53 signature) and serous tubal intraepithelial\ncarcinoma (STIC). Here, we applied RealSeqS to assess aneuploidy in 127 microdissected\ntubal regions. We found nearly all p53 signatures lost the entire Chr17 chromosome, offering a “two-hit” mechanism of both TP53 and BRCA1 in BRCA1 germline mutation carriers. Proliferatively active STICs harbor gains of 19q12 (CCNE1), 19q13.2, 8q24 (MYCyc), or 8q arm, while proliferatively dormant STICs show 22q loss. Based on aneuploidy patterns in a training set (n= 67), we developed an algorithm, REAL-FAST, to classify NFTE and STICs into 5 clusters. In an independent validation set (n= 72), REAL-FAST was able to detect STIC/HGSC with high sensitivity and specificity. Taken together, REAL-FAST promises a molecular test for diagnosing HGSC precursor lesions based on specific aneuploidy patterns.","study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-11-06T14:29:43.769573+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007221","title":"RNAseq of Soft Tissue Sarcomas","description":"Exon capture RNAseq of 25 soft tissue sarcomas.","abstract":"Exon capture RNAseq of 25 soft tissue sarcomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-09T23:30:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007222","title":"Integrated genetic analysis of primary CNS lymphoma","description":null,"abstract":"Immunodeficiency-related Epstein-Barr-virus-positive (EBV+) primary CNS lymphoma (PCNSL) represents a distinct clinical entity with an inferior prognosis compared to EBV--disease. Genetic alterations that drive EBV-related CNS lymphomagenesis remain unclear precluding targeted therapies. In this study, we performed whole-exome sequencing of 5 paired (tumor and germline control) and 13 unpaired (tumor only) EBV+ PCNSL as well as 2 EBV- controls.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-10T06:14:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007223","title":"Whole exome sequencing (WES) of previously untreated AML samples","description":"MNC were isolated from bone of 95 AML patients at initial diagnosis via Ficoll gradient. WES has been performed on all 95 samples.","abstract":"MNC were isolated from bone of 95 AML patients at initial diagnosis via Ficoll gradient. WES has been performed on all 95 samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-10T09:15:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007224","title":"PDAC_phylogenetics__LCM_WGS_","description":"Phylogenetic exploration of the pancreas including normal pancreatic tissue, premalignant lesions, and pancreatic ductal adenocarcinoma resections (tumour and adjacent normal). A range of different approaches will be used including LCM and ribboning with sequencing including LCM-B (whole genome and whole exome) as well as NanoSeq.","abstract":"Deciphering the phylogenetics of pancreatic ductal adenocarcinoma, from normal through to malignant tissue.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007225","title":"PDAC_phylogenetics__LCM_WES_","description":"Phylogenetic exploration of the pancreas including normal pancreatic tissue, premalignant lesions, and pancreatic ductal adenocarcinoma resections (tumour and adjacent normal). A range of different approaches will be used including LCM and ribboning with sequencing including LCM-B (whole genome and whole exome) as well as NanoSeq.","abstract":"Deciphering the phylogenetics of pancreatic ductal adenocarcinoma, from normal through to malignant tissue.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007226","title":"PanIN___PDAC_phylogenetics__EMseq_","description":"Phylogenetic exploration of the pancreas including normal pancreatic tissue, premalignant lesions, and pancreatic ductal adenocarcinoma resections (tumour and adjacent normal). A range of different approaches will be used including LCM and ribboning with sequencing including LCM-B (whole genome and whole exome) as well as NanoSeq.","abstract":"Deciphering the phylogenetics of pancreatic ductal adenocarcinoma, from normal through to malignant tissue.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007227","title":"Analysis of circulating miRNAs for the identification of new prognostic and predictive markers in gastro-entero-pancreatic neuroendocrine tumour (GEP-NET)","description":null,"abstract":"The aim of the study is to analyze the pattern of miRNA expression in the peripheral blood of GEP-NET patients (liquid biopsy) in order to identify a prognostic miRNA signature that correlates with 18FDG–PET status thus, with tumor metabolism and clinical parameeters such as 68Gallium-PET SUVmax.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-10T13:11:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007228","title":"Chromatin_accessibility_profiling_of_PBMC_in_the_ELGH_cohort","description":"This data set contains 10x genomics single cell ATAC profiling of PBMC from the blood donors participating in the East London Genes and Health (ELGH) study. Each individually tagged library contains 20,000 individual PBMC sourced from 10-13 individual donors that require deconvolution of to be analysed separately.     \n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"The Cardinal project is a large scale single cell transcriptomics project analysing human PBMC's. The main aim of the study is to generate a reference data set of gene expression measurements in human immune cells that could be used in quantitative trait loci analysis (QTL). The study will be constructed from several thousand donors from both UK British and South Asia populations enabling the association of rare variants and non-European alleles with changes in gene expression levels in specific cell types. Participants within the study have been extensively phenotyped with genome wide association data sets being generated or available. Enabling the integration of genetic associated changes in gene expression with GWAS for traits and disease. This data set contains 10x genomics single cell ATAC profiling of PBMC from the blood donors (n=&gt;100) participating in the Genes and Health  study. Each individually tagged library contains 20,000 individual PBMC sourced from 10-13 individual donors that require deconvolution of to be analysed separately.     ","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007229","title":"A transcriptomic approach to understand patient susceptibility to pneumonia after abdominal surgery","description":"Rationale\n\tNosocomial infections are a major healthcare challenge, developing in over 20% of patients aged 45 or over undergoing major-abdominal surgery, with postoperative pneumonia associated with an almost five-fold increase in 30-day mortality.  \n\nObjectives\nTo describe immune-pathways and gene-networks altered following major-abdominal surgery and identify transcriptomic patterns associated with postoperative pneumonia. \n\nMethods and Measurements\nFrom a prospective consecutive cohort (n=150) undergoing major-abdominal surgery whole-blood RNA was collected preoperatively and at three time-points postoperatively (2-6, 24 and 48hrs). Twelve patients diagnosed with postoperative pneumonia and 27 matched patients remaining infection-free were identified for analysis with RNA-sequencing.\n\nMain Results\nCompared to preoperative sampling, 3,639 genes were upregulated and 5,043 downregulated at 2-6hrs. Pathway-analysis demonstrated innate-immune activation with neutrophil-degranulation and Toll-like-receptor signalling upregulation alongside adaptive-immune suppression. Cell-type deconvolution of preoperative RNA-sequencing revealed elevated S100A8/9-high neutrophils alongside reduced naïve CD4 T-cells in those later developing pneumonia. Preoperatively, a gene-signature characteristic of neutrophil-degranulation was associated with postoperative pneumonia acquisition (P=0.00092). A previously reported Sepsis Response Signature (SRSq) score, reflecting neutrophil-dysfunction and a more dysregulated host response, at 48hrs postoperatively, differed between patients subsequently developing pneumonia and those remaining infection-free (P=0.045). Analysis of the novel neutrophil gene-signature and SRSq scores in independent major-abdominal surgery and polytrauma cohorts indicated good predictive performance in identifying patients suffering later infection.\n\nConclusions\nMajor-abdominal surgery acutely upregulates innate-immune pathways while simultaneously suppressing adaptive-immune pathways. This is more prominent in patients developing postoperative pneumonia. Preoperative transcriptomic signatures characteristic of neutrophil-degranulation and postoperative SRSq scores may be useful predictors of subsequent pneumonia risk.","abstract":"Rationale\n\tNosocomial infections are a major healthcare challenge, developing in over 20% of patients aged 45 or over undergoing major-abdominal surgery, with postoperative pneumonia associated with an almost five-fold increase in 30-day mortality.  \n\nObjectives\nTo describe immune-pathways and gene-networks altered following major-abdominal surgery and identify transcriptomic patterns associated with postoperative pneumonia. \n\nMethods and Measurements\nFrom a prospective consecutive cohort (n=150) undergoing major-abdominal surgery whole-blood RNA was collected preoperatively and at three time-points postoperatively (2-6, 24 and 48hrs). Twelve patients diagnosed with postoperative pneumonia and 27 matched patients remaining infection-free were identified for analysis with RNA-sequencing.\n\nMain Results\nCompared to preoperative sampling, 3,639 genes were upregulated and 5,043 downregulated at 2-6hrs. Pathway-analysis demonstrated innate-immune activation with neutrophil-degranulation and Toll-like-receptor signalling upregulation alongside adaptive-immune suppression. Cell-type deconvolution of preoperative RNA-sequencing revealed elevated S100A8/9-high neutrophils alongside reduced naïve CD4 T-cells in those later developing pneumonia. Preoperatively, a gene-signature characteristic of neutrophil-degranulation was associated with postoperative pneumonia acquisition (P=0.00092). A previously reported Sepsis Response Signature (SRSq) score, reflecting neutrophil-dysfunction and a more dysregulated host response, at 48hrs postoperatively, differed between patients subsequently developing pneumonia and those remaining infection-free (P=0.045). Analysis of the novel neutrophil gene-signature and SRSq scores in independent major-abdominal surgery and polytrauma cohorts indicated good predictive performance in identifying patients suffering later infection.\n\nConclusions\nMajor-abdominal surgery acutely upregulates innate-immune pathways while simultaneously suppressing adaptive-immune pathways. This is more prominent in patients developing postoperative pneumonia. Preoperative transcriptomic signatures characteristic of neutrophil-degranulation and postoperative SRSq scores may be useful predictors of subsequent pneumonia risk.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-10T16:32:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007230","title":"Multiomic profiling of pleomorphic rhabdomyosarcoma","description":"Rhabdomyosarcoma (RMS) describes rare soft-tissue tumors that exhibit features of skeletal muscle differentiation. The most common subtypes in children are alveolar and embryonal rhabdomyosarcoma, with the alveolar subtype characterized by PAX3/7 fusions. A lesser known and rarer subtype, pleomorphic rhabdomyosarcoma (PRMS), occurs most frequently in adults vetween the ages of 40 and 50. This pleomorphic subtype is often misdiagnosed and little is known about its molecular characterization. Here, we conducted comprehensive genomic, transcriptomic, and methylation profiling of these tumors.","abstract":"Rhabdomyosarcoma (RMS) describes rare soft-tissue tumors that exhibit features of skeletal muscle differentiation. The most common subtypes in children are alveolar and embryonal rhabdomyosarcoma, with the alveolar subtype characterized by PAX3/7 fusions. A lesser known and rarer subtype, pleomorphic rhabdomyosarcoma (PRMS), occurs most frequently in adults vetween the ages of 40 and 50. This pleomorphic subtype is often misdiagnosed and little is known about its molecular characterization. Here, we conducted comprehensive genomic, transcriptomic, and methylation profiling of these tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-10T18:04:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007231","title":"WGS of KCNQ2 R201C patient derived iPSC and its isogenic line","description":null,"abstract":"Using prime editing, we generated an isogenic line of an iPSC line of an individual with a pathogenic KCNQ2 R201C mutation. WGS on the mutant line and two isogenic clones was performed to identify potential off target effects","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-11T12:49:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007232","title":"HCA_Kidney_Disease_CZI_RNA_Managed_Access","description":"Transcriptome analysis of kidney biopsies from patients with kidney disease","abstract":"This project aims to characterise patient kidney biopsies more rigorously than is currently possible, using techniques such as transcriptomics and spatial analysis to define molecular markers of kidney disease which accurately classify patients into different groups on the basis of their underlying pathology. More confident categorisation of disease will ensure patients receive diseasespecific therapy. Specific molecular markers will be investigated to understand if they can help to predict patient outcomes and response to treatment, and whether information about peripheral immune responses or the microbiome can assist with prognostication. Long term, the goal is to be able to clarify the disease mechanisms underpinning pathological changes, potentially enabling the development of novel, targeted treatment strategies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007233","title":"Pilot_For_SCRNA_of_SLE_Mexico","description":"This is a pilot study of 10 samples for single cell RNAseq profiling of lupus patients from Mexico. This will a pilot study aiming to understand the impact of Mexican ancestry in the development of autoimune disease.","abstract":"This is a pilot study of 10 samples for single cell RNAseq profiling of lupus patients from Mexico. This will a pilot study aiming to understand the impact of Mexican ancestry in the development of autoimune disease.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007234","title":"HCA_Kidney_Disease_CZI_Spatial_Managed_Access","description":"Spatial transcriptome analysis of kidney biopsies from patients with kidney disease","abstract":"This project aims to characterise patient kidney biopsies more rigorously than is currently possible, using techniques such as transcriptomics and spatial analysis to define molecular markers of kidney disease which accurately classify patients into different groups on the basis of their underlying pathology. More confident categorisation of disease will ensure patients receive diseasespecific therapy. Specific molecular markers will be investigated to understand if they can help to predict patient outcomes and response to treatment, and whether information about peripheral immune responses or the microbiome can assist with prognostication. Long term, the goal is to be able to clarify the disease mechanisms underpinning pathological changes, potentially enabling the development of novel, targeted treatment strategies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007235","title":"Dataset with genome-wide array data from Algerian Amazigh (Chaoui and Mozabite) and non-Amazigh individuals","description":"In this study we perform a genetic characterization of different Amazigh populations in Algeria and assess the impact of recent demography on their genomes.","abstract":"In this study we perform a genetic characterization of different Amazigh populations in Algeria and assess the impact of recent demography on their genomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-14T20:00:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007236","title":"Whole-Exome Sequences from Imazighen and non-Imazghen from Algeria","description":"Study of high-coverage whole-exome sequences from Amazigh (Tamazight-speakers) and non-Amazigh individuals (Arab-speakers) from Algeria to analyze the impact of demography in functional genomic variation in the complex demographic context of North Africa. Amazigh individuals were sampled in Oum El Bouaghi, Batna, Khenchela, and Ghardaïa, and non-Amazigh individuals were sampled in Algiers.","abstract":"Study of high-coverage whole-exome sequences from Amazigh (Tamazight-speakers) and non-Amazigh individuals (Arab-speakers) from Algeria to analyze the impact of demography in functional genomic variation in the complex demographic context of North Africa. Amazigh individuals were sampled in Oum El Bouaghi, Batna, Khenchela, and Ghardaïa, and non-Amazigh individuals were sampled in Algiers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-14T20:46:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007237","title":"Analysis of a cohort of familial ademomatous polyposis patients bearing APC gene mutation","description":"large number of colorectal adenomas with high risk of evolving into colorectal tumors. Mutations of the Adenomatous polyposis coli (APC) gene is often at the origin of this disease, as well as of a high percentage of spontaneous colorectal tumors. APC is therefore considered a tumor suppressor gene. While the role of APC in intestinal epithelium homeostasis is well characterized, its importance in immune responses remains ill defined. We investigated an array of immune cell features in FAP subjects carrying APC mutations. A group of 12 FAP subjects and age and sex-matched healthy controls were studied. In particular, the expression of 579 immune response genes was analyzed in whole blood cells using the Nanostring nCounter Human Immunology kit v2. (Cuche C. et al. Frontiers in Immunology, 2023, in press)","abstract":"large number of colorectal adenomas with high risk of evolving into colorectal tumors. Mutations of the Adenomatous polyposis coli (APC) gene is often at the origin of this disease, as well as of a high percentage of spontaneous colorectal tumors. APC is therefore considered a tumor suppressor gene. While the role of APC in intestinal epithelium homeostasis is well characterized, its importance in immune responses remains ill defined. We investigated an array of immune cell features in FAP subjects carrying APC mutations. A group of 12 FAP subjects and age and sex-matched healthy controls were studied. In particular, the expression of 579 immune response genes was analyzed in whole blood cells using the Nanostring nCounter Human Immunology kit v2. (Cuche C. et al. Frontiers in Immunology, 2023, in press)","study_type":"Other","pubmed_ids":[35417240,37533857],"external_links":null,"is_released":true,"released_date":"2023-05-15T10:40:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007238","title":"cfDNA dataset from the urine supernatant of ovarian cancer patients and healthy controls","description":"Background\n\nOvarian cancer is the deadliest gynecological malignancy worldwide, due to frequent diagnosis at advanced stage. Simple and non-invasive methods for earlier and accurate detection are urgently needed. Here, the presence of tumor-derived DNA in home-collected urine, cervicovaginal self-samples and clinician-taken cervical scrapes of ovarian cancer patients was explored by DNA methylation and copy number analysis.\n\nMethods\n\nA total of 428 samples (urine, cervicovaginal self-samples, and clinician-taken cervical scrapes) of 110 healthy controls and 54 patients with benign (n=25) or malignant (n=29) ovarian masses were analyzed. Different urine fractions were examined (full void urine, urine supernatant, and urine sediment). All samples were tested for 12 methylation markers by quantitative methylation-specific PCR. Shallow whole-genome sequencing was performed to detect copy number aberrations and verify the presence of tumor-derived DNA.\n\nResults\n\nFull void urine was most discriminatory between healthy controls and ovarian cancer patients (C2CD4D, p=0.008; CDO1, p=0.022; MAL, p=0.008), followed by cervical scrapes (C2CD4D, p=0.001; CDO1, p=0.004). A significant difference between benign and malignant ovarian masses was only observed for GHSR in the urine sediment (p=0.024). Methylation levels in cervicovaginal self-samples did not discriminate between healthy controls, benign and malignant ovarian masses. Copy number changes were identified in 17% of urine supernatant samples and smaller fragment sizes were seen in urine supernatant samples with a high tumor fraction.\n\nConclusions\n\nThis study demonstrates the presence of ovarian cancer-derived DNA in home-collected urine. Additional studies are warranted to further explore the clinical applicability of this approach.","abstract":"Background\n\nOvarian cancer is the deadliest gynecological malignancy worldwide, due to frequent diagnosis at advanced stage. Simple and non-invasive methods for earlier and accurate detection are urgently needed. Here, the presence of tumor-derived DNA in home-collected urine, cervicovaginal self-samples and clinician-taken cervical scrapes of ovarian cancer patients was explored by DNA methylation and copy number analysis.\n\nMethods\n\nA total of 428 samples (urine, cervicovaginal self-samples, and clinician-taken cervical scrapes) of 110 healthy controls and 54 patients with benign (n=25) or malignant (n=29) ovarian masses were analyzed. Different urine fractions were examined (full void urine, urine supernatant, and urine sediment). All samples were tested for 12 methylation markers by quantitative methylation-specific PCR. Shallow whole-genome sequencing was performed to detect copy number aberrations and verify the presence of tumor-derived DNA.\n\nResults\n\nFull void urine was most discriminatory between healthy controls and ovarian cancer patients (C2CD4D, p=0.008; CDO1, p=0.022; MAL, p=0.008), followed by cervical scrapes (C2CD4D, p=0.001; CDO1, p=0.004). A significant difference between benign and malignant ovarian masses was only observed for GHSR in the urine sediment (p=0.024). Methylation levels in cervicovaginal self-samples did not discriminate between healthy controls, benign and malignant ovarian masses. Copy number changes were identified in 17% of urine supernatant samples and smaller fragment sizes were seen in urine supernatant samples with a high tumor fraction.\n\nConclusions\n\nThis study demonstrates the presence of ovarian cancer-derived DNA in home-collected urine. Additional studies are warranted to further explore the clinical applicability of this approach.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-15T10:54:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007239","title":"Genetic scoring guide for personalized risk assessment in pediatric B-cell precursor Acute Lymphoblastic Leukemia","description":"In this study a next-generation sequencing based method was applied to comprehensively screen for recurrent, disease-relevant copy number aberrations in a cohort of Hungarian patients. Diagnostic bone marrow samples from 260 children with B-cell acute lymphoblastic leukemia and were investigated by digital multiplex ligation-dependent probe amplification using the disease-specific D007 probemix. Whole chromosome gains and losses, as well as subchromosomal copy number aberrations were simultaneously profiled.","abstract":"In this study a next-generation sequencing based method was applied to comprehensively screen for recurrent, disease-relevant copy number aberrations in a cohort of Hungarian patients. Diagnostic bone marrow samples from 260 children with B-cell acute lymphoblastic leukemia and were investigated by digital multiplex ligation-dependent probe amplification using the disease-specific D007 probemix. Whole chromosome gains and losses, as well as subchromosomal copy number aberrations were simultaneously profiled.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-15T11:32:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007240","title":"Enhancer plasticity in endometrial tumorigenesis demarcates non-coding driver mutations and alterations in 3D genome organization to boost oncogene expression","description":"Understand whether and how ERα can drive endometrial tumorigenesis. Study the mechanisms that lead to endometrial tumor progression and metastasis formation.","abstract":"Understand whether and how ERα can drive endometrial tumorigenesis. Study the mechanisms that lead to endometrial tumor progression and metastasis formation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-15T16:25:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007241","title":"Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease","description":"Population level variation and molecular mechanisms behind insulin secretion in response to carbohydrate, protein, and fat remain uncharacterized despite ramifications for personalized nutrition. We now define prototypical insulin secretion dynamics in response to the three macronutrients in islets from 140 cadaveric donors, including those diagnosed with type 2 diabetes. We leverage the insulin response heterogeneity and use transcriptomics and proteomics to identify molecular pathways of specific nutrient responsiveness. Surprisingly, we find robust insulin secretion to fatty acid stimulus in ~8% of donors, challenging the idea that fat has negligible effects on insulin release. Distinct islet proteomes with differences in metabolic signalling networks convey this hyper-responsiveness to fat relative to carbohydrate. By comparing human islets to human embryonic stem cell-derived islet clusters, we show that, unlike glucose-responsiveness, fat hyper-responsiveness is equivalent and may be a hallmark of functionally immature cells. Our study represents the first comparison of dynamic responses to nutrients and multi-omics analysis in human insulin secreting cells. Responses of different people’s islets to carbohydrate, protein, and fat lay the groundwork for personalized nutrition.","abstract":"Population-level variation and molecular mechanisms behind insulin secretion in response to carbohydrates, protein, and fat remain uncharacterized despite implications for personalized therapeutic nutrition. We now define prototypical insulin secretion dynamics in response to the three macronutrients in islets from over 100 cadaveric donors, including those previously diagnosed with type 2 diabetes. This dataset includes the transcriptomic sequencing data from the islets of 96 donors.","study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-05-15T21:00:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007242","title":"Single-cell decoding of drug induced transcriptomic reprogramming in triple negative breast cancers","description":"Background\n\nThe encoding of cell intrinsic drug resistance states in breast cancer reflects the contributions of genomic and non-genomic variations and requires accurate estimation of clonal fitness from co-measurement of transcriptomic and genomic data. Somatic copy number (CN) variation is the dominant mutational mechanism leading to transcriptional variation and notably contributes to platinum chemotherapy resistance cell states. Here, we deploy time series measurements of triple negative breast cancer (TNBC) single-cell transcriptomes, along with co-measured single-cell CN fitness, identifying genomic and transcriptomic mechanisms in drug associated transcriptional cell states.\n\nResults\n\nWe present scRNA-seq data (53,641 filtered cells) from serial passaging TNBC patient-derived xenograft (PDX) experiments spanning 2.5 years, matched with genomic single-cell CN data from the same samples. Our findings reveal distinct clonal responses within TNBC tumors exposed to platinum. Clones with high drug fitness undergo clonal sweeps and show subtle transcriptional reversion, while those with weak fitness exhibit dynamic transcription upon drug withdrawal. Pathway analysis highlights convergence on epithelial-mesenchymal transition and cytokine signaling, associated with resistance. Furthermore, pseudotime analysis demonstrates hysteresis in transcriptional reversion, indicating generation of new intermediate transcriptional states upon platinum exposure.\n\nConclusions\n\nWithin a polyclonal tumor, clones with strong genotype-associated fitness under platinum remained fixed, minimizing transcriptional reversion upon drug withdrawal. Conversely, clones with weaker fitness display non-genomic transcriptional plasticity. This suggests CN-associated and CN-independent transcriptional states could both contribute to platinum resistance. The dominance of genomic or non-genomic mechanisms within polyclonal tumors has implications for drug sensitivity, restoration and re-treatment strategies.","abstract":"Background\n\nThe encoding of cell intrinsic drug resistance states in breast cancer reflects the contributions of genomic and non-genomic variations and requires accurate estimation of clonal fitness from co-measurement of transcriptomic and genomic data. Somatic copy number (CN) variation is the dominant mutational mechanism leading to transcriptional variation and notably contributes to platinum chemotherapy resistance cell states. Here, we deploy time series measurements of triple negative breast cancer (TNBC) single-cell transcriptomes, along with co-measured single-cell CN fitness, identifying genomic and transcriptomic mechanisms in drug associated transcriptional cell states.\n\nResults\n\nWe present scRNA-seq data (53,641 filtered cells) from serial passaging TNBC patient-derived xenograft (PDX) experiments spanning 2.5 years, matched with genomic single-cell CN data from the same samples. Our findings reveal distinct clonal responses within TNBC tumors exposed to platinum. Clones with high drug fitness undergo clonal sweeps and show subtle transcriptional reversion, while those with weak fitness exhibit dynamic transcription upon drug withdrawal. Pathway analysis highlights convergence on epithelial-mesenchymal transition and cytokine signaling, associated with resistance. Furthermore, pseudotime analysis demonstrates hysteresis in transcriptional reversion, indicating generation of new intermediate transcriptional states upon platinum exposure.\n\nConclusions\n\nWithin a polyclonal tumor, clones with strong genotype-associated fitness under platinum remained fixed, minimizing transcriptional reversion upon drug withdrawal. Conversely, clones with weaker fitness display non-genomic transcriptional plasticity. This suggests CN-associated and CN-independent transcriptional states could both contribute to platinum resistance. The dominance of genomic or non-genomic mechanisms within polyclonal tumors has implications for drug sensitivity, restoration and re-treatment strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-16T00:17:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007243","title":"Early and longlasting epigenetic damage to muscle stem cells in critical illness myopathy","description":null,"abstract":"Critical illness myopathy (CIM) is a devastating acquired muscle wasting disease caused by prolonged immobilization during critical illness. The impact on rehabilitation, hospital costs, and quality of life is enormous. Muscular atrophy persists without known cause. We asked whether satellite cells, the stem cells of skeletal muscle, lose their ability to regenerate muscle because of injury during the onset of CIM. We performed within the first days after admission to the ICU skeletal muscle biopsies in 35 critically ill patients without preexisting neuromuscular disorders with very high risk of developing CIM. Skeletal muscle stem cells were isolated, amplified and characterized for their myogenic profile. The epigenetic fingerprint was characterized by RNA-Seq, immunofluorescence, analysis of DNA breaks, and ATAC-Seq analysis. CIM primary early myoblasts were also transplanted into immunodeficient NOG mice to assess their regenerative potential. Compared to normal and non-CIM-ICU controls, we found dramatic epigenetic changes in CIM samples . The entire chromatin structure and histone 1 was lost leading to DNA breaks. Functionally, CIM myoblasts had a defect in building new muscle fibers.  Our results demonstrate global and lasting epigenetic changes in human muscle stem cells that occur during the first days of critical illness, therefore providing a valid explanation for the insufficient capacity to regenerate muscle strength in CIM patients.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007244","title":"Genomic analyses to identify metabolic vulnerabilities","description":"Genomic analyses to identify metabolic vulnerabilities on PDX samples","abstract":"Genomic analyses to identify metabolic vulnerabilities on PDX samples","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-16T10:24:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007245","title":"Pre-existing immunity drives the response to neoadjuvant chemotherapy in esophageal adenocarcinoma","description":"Esophageal adenocarcinoma (EAC) is a highly aggressive tumor. Patients with locally advanced disease undergo neoadjuvant chemotherapy (nCT) before surgery, however fewer than 30% of treated patients achieve a pathological complete response associated with increased 5-year overall survival. We set out to elucidate the mechanisms the response to nCT by multi-dimensional profiling of pre-treatment tumor biopsies and blood samples from EAC patients. In particular we performed whole exome sequencing (WES) and RNAseq on n=26 baseline EAC tumor; two additional EAC samples underwent only WES. WES on matched peripheral blood mononuclear cells (PBMCs) were used as germline control.","abstract":"Esophageal adenocarcinoma (EAC) is a highly aggressive tumor. Patients with locally advanced disease undergo neoadjuvant chemotherapy (nCT) before surgery, however fewer than 30% of treated patients achieve a pathological complete response associated with increased 5-year overall survival. We set out to elucidate the mechanisms the response to nCT by multi-dimensional profiling of pre-treatment tumor biopsies and blood samples from EAC patients. In particular we performed whole exome sequencing (WES) and RNAseq on n=26 baseline EAC tumor; two additional EAC samples underwent only WES. WES on matched peripheral blood mononuclear cells (PBMCs) were used as germline control.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-16T10:29:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007246","title":"Aplastic_anaemia_methylation","description":"The somatic mutational landscape of Aplastic anaemia colonies will be characterized using EMSEQ. Samples have been sourced from the Cambridge Biobank.","abstract":"The somatic mutational landscape of of Aplastic anaemia colonies will be characterized using EMSEQ. Samples have been sourced from the Cambridge Biobank.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007247","title":"Transcriptomic analysis of cell-of-origin CNS neuroblastoma, FOXR2 activated","description":"The transcription factor FOXR2 is the universal driver of childhood central nervous system neuroblastoma, FOXR2 activated (NB-FOXR2). NB-FOXR2 tumors arise exclusively in the brain hemispheres, and despite morphological similarities to other pediatric brain tumors, they are a molecularly distinct entity based on DNA methylation profiling. The cell-of-origin is unknown. Here, we profiled a cohort of rare NB-FOXR2 tumors by bulk and single-cell transcriptomics. Through systematic comparative analyses, we delineate tumor transcriptional states and candidate cell-of-origin. More broadly, we demonstrate systematic molecular profiling of childhood cancers to orient oncogenic targeting for in vivo modeling, a critical resource for the study of rare tumors and development of therapeutics.","abstract":"The transcription factor FOXR2 is the universal driver of childhood central nervous system neuroblastoma, FOXR2 activated (NB-FOXR2). NB-FOXR2 tumors arise exclusively in the brain hemispheres, and despite morphological similarities to other pediatric brain tumors, they are a molecularly distinct entity based on DNA methylation profiling. The cell-of-origin is unknown. Here, we profiled a cohort of rare NB-FOXR2 tumors by bulk and single-cell transcriptomics. Through systematic comparative analyses, we delineate tumor transcriptional states and candidate cell-of-origin. More broadly, we demonstrate systematic molecular profiling of childhood cancers to orient oncogenic targeting for in vivo modeling, a critical resource for the study of rare tumors and development of therapeutics.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-16T17:23:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007248","title":"Single molecule genome-wide mutation profiles of cell-free DNA for non-invasive detection of cancer","description":"Somatic mutations are a hallmark of tumorigenesis and may be useful for non-invasive diagnosis of cancer. We analyzed whole-genome sequencing (WGS) data from 2,511 individuals in the Pan-Cancer Analysis of Whole Genomes (PCAWG) study as well as 489 individuals from four prospective cohorts and found distinct regional and mutation type specific frequencies in tissue and cell-free DNA (cfDNA) of cancer patients that were associated with replication timing and other chromatin features. A machine learning model using genome-wide mutational profiles combined with other features and followed by CT imaging detected &gt;90% of lung cancer patients, including those with stage I and II disease. The fixed model was validated in an independent cohort, detected patients with cancer earlier than standard approaches, and could be used to monitor response to therapy. This approach lays the groundwork for non-invasive cancer detection using genome-wide mutation features that may facilitate cancer screening and monitoring.","abstract":"Somatic mutations are a hallmark of tumorigenesis and may be useful for non-invasive diagnosis of cancer. We analyzed whole-genome sequencing (WGS) data from 2,511 individuals in the Pan-Cancer Analysis of Whole Genomes (PCAWG) study as well as 489 individuals from four prospective cohorts and found distinct regional and mutation type specific frequencies in tissue and cell-free DNA (cfDNA) of cancer patients that were associated with replication timing and other chromatin features. A machine learning model using genome-wide mutational profiles combined with other features and followed by CT imaging detected &gt;90% of lung cancer patients, including those with stage I and II disease. The fixed model was validated in an independent cohort, detected patients with cancer earlier than standard approaches, and could be used to monitor response to therapy. This approach lays the groundwork for non-invasive cancer detection using genome-wide mutation features that may facilitate cancer screening and monitoring.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-16T19:06:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007249","title":"Whole genome sequencing of patients with or at risk for HCC","description":"Liver cancer is a major cause of cancer mortality worldwide. Screening individuals at high risk, including those with cirrhosis and viral hepatitis, provides an avenue for improved survival, but current screening methods are inadequate. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome analyses to evaluate 724 individuals from the United States, the European Union, or Hong Kong with hepatocellular carcinoma (HCC) or who were at average or high-risk for HCC. Using a machine learning model that incorporated multifeature fragmentome data, the sensitivity for detecting cancer was 88% in an average-risk population at 98% specificity and 85% among high-risk individuals at 80% specificity. We validated these results in an independent population. cfDNA fragmentation changes reflected genomic and chromatin changes in liver cancer, including from transcription factor binding sites. These findings provide a biological basis for changes in cfDNA fragmentation in patients with liver cancer and provide an accessible approach for noninvasive cancer detection.","abstract":"Liver cancer is a major cause of cancer mortality worldwide. Screening individuals at high risk, including those with cirrhosis and viral hepatitis, provides an avenue for improved survival, but current screening methods are inadequate. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome analyses to evaluate 724 individuals from the United States, the European Union, or Hong Kong with hepatocellular carcinoma (HCC) or who were at average or high-risk for HCC. Using a machine learning model that incorporated multifeature fragmentome data, the sensitivity for detecting cancer was 88% in an average-risk population at 98% specificity and 85% among high-risk individuals at 80% specificity. We validated these results in an independent population. cfDNA fragmentation changes reflected genomic and chromatin changes in liver cancer, including from transcription factor binding sites. These findings provide a biological basis for changes in cfDNA fragmentation in patients with liver cancer and provide an accessible approach for noninvasive cancer detection.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-16T19:18:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007250","title":"H3Africa - Genomic Characterization and Surveillance of Microbial Threats in West Africa","description":"Viral diseases are remarkably heterogeneous in their presentation and clinical course. Although diseases such as Lassa Fever and Ebola Virus Disease are thought to be severe and rapidly fatal, they can often present with mild symptoms or remain asymptomatic. Host genetic variability is likely an important mediator of this heterogeneity. Complete characterization of the clinical, laboratory, and host genetic features of these illnesses is not only imperative to rapid diagnosis and effective clinical care, but also important for further scientific study. In this project, we propose to address this need through deep characterization of the clinical and laboratory features of viral disease and through study of genetic mediators of resistance to Lassa Fever and Ebola Virus Disease. Will carry out deep clinical characterization and laboratory assessment of viral febrile cases at two West African Collaborative Centers, and will use this data to develop prognostic models using cutting-edge tools in exploratory data visualization and machine learning. Investigate host genetic factors of Lassa Fever and Ebola Virus Disease through genome-wide association studies. We will then develop field-deployable genotyping assays for the top-associated variants, and apply them in new cohorts to replicate our findings and investigate patterns of genetic resistance in clinical subgroups. This project can shed light on the clinical manifestations of viral illness and their host genetic mediators, leading to potential new insights in disease biology and pathophysiology. We will also create a rich resource of clinical, laboratory, and genetic data for these illnesses in two countries in West Africa, which will serve as a foundation for advancing the clinical care and scientific study of viral disease in the region.","abstract":"Viral diseases are remarkably heterogeneous in their presentation and clinical course. Although diseases such as Lassa Fever and Ebola Virus Disease are thought to be severe and rapidly fatal, they can often present with mild symptoms or remain asymptomatic. Host genetic variability is likely an important mediator of this heterogeneity. Complete characterization of the clinical, laboratory, and host genetic features of these illnesses is not only imperative to rapid diagnosis and effective clinical care, but also important for further scientific study. In this project, we propose to address this need through deep characterization of the clinical and laboratory features of viral disease and through study of genetic mediators of resistance to Lassa Fever and Ebola Virus Disease. Will carry out deep clinical characterization and laboratory assessment of viral febrile cases at two West African Collaborative Centers, and will use this data to develop prognostic models using cutting-edge tools in exploratory data visualization and machine learning. Investigate host genetic factors of Lassa Fever and Ebola Virus Disease through genome-wide association studies. We will then develop field-deployable genotyping assays for the top-associated variants, and apply them in new cohorts to replicate our findings and investigate patterns of genetic resistance in clinical subgroups. This project can shed light on the clinical manifestations of viral illness and their host genetic mediators, leading to potential new insights in disease biology and pathophysiology. We will also create a rich resource of clinical, laboratory, and genetic data for these illnesses in two countries in West Africa, which will serve as a foundation for advancing the clinical care and scientific study of viral disease in the region.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-17T08:05:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007251","title":"Targeted_NanoSeq__FAP_cohort_","description":"Targeted NanoSeq of fresh buccal swabs obtained from patients with inherited tumour predisposition syndromes (Familial Adenomatous Polyposis (FAP)). A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the buccal driver landscape in patients with inherited tumour predisposition syndromes (FAP).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007252","title":"Deciphering the molecular basis of ophtalmogenetic diseases: sequencing the whole genome using a long reads approach.","description":null,"abstract":"The principal objective of this project is to delve deeper into the molecular basis of RD by exploring the whole genome using long reads sequencing. We selected 36 samples from patients that have been subject of clinical exome, WES and/or WGS sequencing, are still with no conclusive diagnosis, and phenotypes could be explained by the presence of a structural variant. We used nanopore long reads sequencing due to its capability to explore non-coding regions as well as to search for complex structural variants besides the usual single variants calling.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007253","title":"Clonal_selection_after_gene_therapy_in_SCD___Duplex_sequencing","description":"This study includes the targeted duplex sequencing data relating to this study.  A custom targeted panel was used including 29 AML-associated genes, and a set of mutations from driver-containing clones that were sequenced during the WGS tree-building phase of the study.  Targeted sequencing is performed on each of 6 individuals included at the study at at least 3 time points per individual: one prior to gene therapy, and two post-therapy time points.","abstract":"Gene therapy (GT) provides a potentially curative treatment option for patients with sickle cell disease (SCD). However, the occurrence of myeloid malignancies in clinical trials has prompted concern, with several postulated mechanisms. To interrogate these, we used hematopoietic stem cell (HSC) clonal tracking by whole genome sequencing to map the somatic mutation and clonal landscape of gene modified and unmodified HSCs. Whole genome sequencing was performed on 2,592 single stem and progenitor cell-derived colonies from six SCD patients at pre- and post-GT timepoints. Our results showed that pre-GT phylogenetic trees in SCD are highly polyclonal and mutation burdens per cell were elevated in some, but not all, patients. The number of engrafting clones active at ≤3 years post-transplantation varied between 3,000 to 80,000. Post-GT, no clonal expansions were identified amongst gene modified or unmodified cells; however, an increased frequency of potential driver mutations associated with myeloid neoplasms or clonal hematopoiesis (DNMT3A- and EZH2-mutated clones in particular) were seen in both genetically modified and unmodified cells suggesting positive selection of mutant clones during gene therapy. This work sheds light on the mutational landscape and HSC clonal dynamics in gene therapy for SCD and highlights enhanced fitness of some HSCs harboring pre-existing driver mutations following gene therapy. Future studies should define the long-term fate of mutant clones including any contribution to expansions associated with myeloid neoplasms.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-18T12:29:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007254","title":"Transcriptomics identifies blunted immunomodulatory effects of vitamin D in people with multiple sclerosis","description":"Vitamin D deficiency is a risk factor for developing multiple sclerosis (MS). However, the immune effects of vitamin D in people with MS are not well understood. We analyzed transcriptomic datasets generated by RNA sequencing of immune cell subsets (CD4+, CD8+ T cells, B cells, monocytes) from 33 healthy controls and 33 untreated MS cases. We utilized a traditional bioinformatic pipeline and weighted gene co-expression network analysis (WGCNA) to determine genes and pathways correlated with endogenous vitamin D. In controls, CD4+ and CD8+ T cells had 1079 and 1188 genes, respectively, whose expressions were correlated with plasma 25-hydroxyvitamin D level (P&lt;0.05). Functional enrichment analysis identified association with TNF-alpha and MAPK signaling. In CD4+ T cells of controls, vitamin D level was associated with expression levels of several genes proximal to multiple sclerosis risk loci (P=0.01). Genes differentially associated with endogenous vitamin D by case-control status were enriched in TNF-alpha signaling via NF-κB. WGCNA suggested a blunted response to vitamin D in cases relative to controls. Collectively, our findings provide further evidence for the immune effects of vitamin D, and demonstrate a differential immune response to vitamin D in cases relative to controls, highlighting a possible mechanism contributing to MS pathophysiology.","abstract":"Vitamin D deficiency is a risk factor for developing multiple sclerosis (MS). However, the immune effects of vitamin D in people with MS are not well understood. We analyzed transcriptomic datasets generated by RNA sequencing of immune cell subsets (CD4+, CD8+ T cells, B cells, monocytes) from 33 healthy controls and 33 untreated MS cases. We utilized a traditional bioinformatic pipeline and weighted gene co-expression network analysis (WGCNA) to determine genes and pathways correlated with endogenous vitamin D. In controls, CD4+ and CD8+ T cells had 1079 and 1188 genes, respectively, whose expressions were correlated with plasma 25-hydroxyvitamin D level (P&lt;0.05). Functional enrichment analysis identified association with TNF-alpha and MAPK signaling. In CD4+ T cells of controls, vitamin D level was associated with expression levels of several genes proximal to multiple sclerosis risk loci (P=0.01). Genes differentially associated with endogenous vitamin D by case-control status were enriched in TNF-alpha signaling via NF-κB. WGCNA suggested a blunted response to vitamin D in cases relative to controls. Collectively, our findings provide further evidence for the immune effects of vitamin D, and demonstrate a differential immune response to vitamin D in cases relative to controls, highlighting a possible mechanism contributing to MS pathophysiology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-19T08:48:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007255","title":"Colon adenomas and adenocarcinomas and matched mucosae","description":"Whole exome sequencing in sporadic colorectal cancers (CRC) and advanced adenomas (Ad-As), and their paired healthy mucosa, for a deeper understanding of the biology of this cancer.","abstract":"Whole exome sequencing in sporadic colorectal cancers (CRC) and advanced adenomas (Ad-As), and their paired healthy mucosa, for a deeper understanding of the biology of this cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-19T10:22:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007256","title":"Low_input_RNA_seq_oesophagus","description":"We wish to understand changes in the transcriptome of the oesophageal epithelium both through ageing and under various selection pressures.","abstract":"We wish to understand changes in the transcriptome of the oesophageal epithelium both through ageing and under various selection pressures.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007257","title":"Methylome profiling of epithelioid sarcoma","description":"Explore the methylome landscape of epithelioid sarcoma using array data.","abstract":"Explore the methylome landscape of epithelioid sarcoma using array data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-20T06:31:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007258","title":"BRCA-deficiency/HRD in individuals with HBOC","description":null,"abstract":"Individuals with a germline pathogenic variant (gPV) in BRCA1 or BRCA2 are at a high hereditary risk to develop breast and ovarian carcinomas with BRCA-deficiency and Homologous Recombination Deficiency (HRD) that can be detected by genomic scars such as Large-Scale State Transitions (LSTs). These phenotypes renders the tumors sensitive to PARP inhibitors. Here, we aim to investigate the fraction of non-breast and non-ovarian malignancies that have BRCA-deficiency and HRD features. From Dutch pathology departments non-breast and non-ovarian malignancies were collected, which were investigated for somatic second hit alterations via targeted next-generation sequencing (n=180) and for the presence of HRD via shallow whole genome sequencing (n=192).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007259","title":"An isogenic human iPSC model unravels neurodevelopmental abnormalities in SMA","description":"Whether neurodevelopmental defects underlie the selective neuronal death that characterizes neurodegenerative diseases is becoming an intriguing question. To address it, we focused on the motor neuron (MN) disease Spinal Muscular Atrophy (SMA), caused by reduced levels of the ubiquitous protein SMN. Taking advantage of the first isogenic human induced pluripotent stem cell-derived SMA model that we have generated and a spinal cord organoid system, here we report that the relative and temporal expression of early neural progenitor and MN markers is altered in SMA. Furthermore, the corrected isogenic controls only partially reverse these abnormalities. These findings raise the relevant clinical implication that SMN-increasing treatments might not fully amend SMA pathological phenotypes. The approach we have taken demonstrates that the discovery of new disease mechanisms is greatly improved by using human isogenic models. Moreover, our study implies that SMA has a developmental component that might trigger the MN degeneration.","abstract":"Whether neurodevelopmental defects underlie the selective neuronal death that characterizes neurodegenerative diseases is becoming an intriguing question. To address it, we focused on the motor neuron (MN) disease Spinal Muscular Atrophy (SMA), caused by reduced levels of the ubiquitous protein SMN. Taking advantage of the first isogenic human induced pluripotent stem cell-derived SMA model that we have generated and a spinal cord organoid system, here we report that the relative and temporal expression of early neural progenitor and MN markers is altered in SMA. Furthermore, the corrected isogenic controls only partially reverse these abnormalities. These findings raise the relevant clinical implication that SMN-increasing treatments might not fully amend SMA pathological phenotypes. The approach we have taken demonstrates that the discovery of new disease mechanisms is greatly improved by using human isogenic models. Moreover, our study implies that SMA has a developmental component that might trigger the MN degeneration.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-22T19:57:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007260","title":"Comprehensive Profiling of the Human Fecal Proteome from IBD Patients with DIA-MS Enables Evaluation of Disease-Relevant Proteins","description":null,"abstract":"Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is characterized by chronic gastrointestinal inflammation. A high unmet need exists for non-invasive biomarkers in IBD to detect mucosal inflammation to monitor changes in disease severity and guide treatment decisions. Fecal proteomics has the potential to allow frequent, non-invasive monitoring of biomarkers in stool of IBD patients, however the fecal proteome remains underexplored. Here a data-independent acquisition LC-MS/MS approach was used to profile the human fecal proteome in two independent cohorts of IBD patients and healthy controls (HC) to identify non-invasive biomarkers reflective of disease activity. 688 human proteins were quantified, with 523 measured in both cohorts. In UC stool 96 proteins were differentially abundant and in CD stool 126 proteins were differentially abundant compared to HC stool (absolute log2 fold change &gt;1, p-value &lt;0.05). Many of these fecal proteins are associated with infiltrating immune cells and ulceration/rectal bleeding, which are hallmarks of IBD pathobiology. Mapping of the identified fecal proteins to a whole blood single-cell RNA sequencing data set revealed the involvement of various immune cell subsets to the IBD fecal proteome. Findings from this study not only confirmed the presence of established fecal biomarkers for IBD, such as calprotectin and lactoferrin, but also revealed new fecal proteins from multiple pathways known to be dysregulated in IBD. These novel proteins could serve as potential non-invasive biomarkers to monitor specific aspects of IBD disease activity which could expedite clinical development of novel therapeutic targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007261","title":"Spatial tumor microenvironment characterization and outcome of relapsed/refractory classic Hodgkin lymphoma","description":"About half of relapsed or refractory classic Hodgkin lymphoma (r/r CHL) patients succumb to their disease after high dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT). Here, we aimed at describing spatially resolved tumor microenvironment (TME) ecosystems to establish novel biomarkers associated with treatment failure in r/r CHL.","abstract":"About half of relapsed or refractory classic Hodgkin lymphoma (r/r CHL) patients succumb to their disease after high dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT). Here, we aimed at describing spatially resolved tumor microenvironment (TME) ecosystems to establish novel biomarkers associated with treatment failure in r/r CHL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-23T07:03:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007262","title":"Gene expression of neutrophils in response to Mtb infection in persons living with HIV","description":null,"abstract":"To determine if there is differential gene expression response to Mycobacterium tuberculosis in neutrophils from persons living with HIV who remain tuberculin skin test (TST) and inteferon gamma release assay (IGRA) negative and have no tuberculosis history (HITTIN) compared to persons living with HIV and no previous TB but TST and IGRA positive (HIT).","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-23T09:17:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007263","title":"Cardiovascular disease biomarkers derived from circulating cell-free DNA methylation","description":"Acute coronary syndrome (ACS) remains a major cause of worldwide mortality. The syndrome occurs when blood flow to the heart muscle is decreased or blocked, causing muscle tissues to die or malfunction. There are three main types of ACS: Non-ST-elevation myocardial infarction, ST-elevation myocardial infarction, and unstable angina. The treatment depends on the type of ACS, and this is decided by a combination of clinical findings, such as electrocardiogram and plasma biomarkers. Circulating cell-free DNA (ccfDNA) is proposed as an additional marker for ACS since the damaged tissues can release DNA to the bloodstream. We used ccfDNA methylation profiles for differentiating between the ACS types and provided computational tools to repeat similar analysis for other diseases. We leveraged cell type specificity of DNA methylation to deconvolute the ccfDNA cell types of origin and to find methylation-based biomarkers that stratify patients. We identified hundreds of methylation markers associated with ACS types and validated them in an independent cohort. Many such markers were associated with genes involved in cardiovascular conditions and inflammation. ccfDNA methylation showed promise as a non-invasive diagnostic for acute coronary events. These methods are not limited to acute events, and may be used for chronic cardiovascular diseases as well.","abstract":"Acute coronary syndrome (ACS) remains a major cause of worldwide mortality. The syndrome occurs when blood flow to the heart muscle is decreased or blocked, causing muscle tissues to die or malfunction. There are three main types of ACS: Non-ST-elevation myocardial infarction, ST-elevation myocardial infarction, and unstable angina. The treatment depends on the type of ACS, and this is decided by a combination of clinical findings, such as electrocardiogram and plasma biomarkers. Circulating cell-free DNA (ccfDNA) is proposed as an additional marker for ACS since the damaged tissues can release DNA to the bloodstream. We used ccfDNA methylation profiles for differentiating between the ACS types and provided computational tools to repeat similar analysis for other diseases. We leveraged cell type specificity of DNA methylation to deconvolute the ccfDNA cell types of origin and to find methylation-based biomarkers that stratify patients. We identified hundreds of methylation markers associated with ACS types and validated them in an independent cohort. Many such markers were associated with genes involved in cardiovascular conditions and inflammation. ccfDNA methylation showed promise as a non-invasive diagnostic for acute coronary events. These methods are not limited to acute events, and may be used for chronic cardiovascular diseases as well.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-23T10:29:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007264","title":"Molecular EPISTOP: Comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years","description":null,"abstract":"We present a comprehensive multi-omic analysis of the EPISTOP prospective clinical trial of early intervention with vigabatrin for pre-symptomatic epilepsy treatment in Tuberous Sclerosis Complex (TSC), in which 93 infants with TSC were followed from birth to age 2 years, seeking biomarkers of epilepsy development. Vigabatrin had profound effects on many metabolites, increasing serum deoxycytidine monophosphate (dCMP) levels 52-fold. Most serum proteins and metabolites, and blood RNA species showed significant change with age. Thirty-nine proteins, metabolites, and genes showed significant differences between age-matched control and TSC infants. Six also showed a progressive difference in expression between control, TSC without epilepsy, and TSC with epilepsy groups. A multivariate approach using enrollment samples identified multiple 3-variable predictors of epilepsy, with the best having a positive predictive value of 0.987.  This rich dataset will enable further discovery and analysis of developmental effects, and associations with seizure development in TSC.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007265","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__RCC_SBS12_study","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Grand Challenges award, funded by Cancer Research UK.\n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, head and neck, bladder, gall bladder, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \n\nThis sub-project will specifically investigate SBS12.\n\nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Grand Challenges Award, funded by Cancer Research UK. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, head and neck, bladder, gall bladder, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \n\nThis sub-project will specifically investigate SBS12.\n\nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007266","title":"Somatic_mutation_in_edited_cholangiocyte_organoids__Targeted_NanoSeq_","description":"Characterisation of mutation rates and patterns in edited human cholangiocyte organoids (Targeted NanoSeq)","abstract":"Characterisation of mutation rates and patterns in edited human cholangiocyte organoids (Targeted NanoSeq)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-24T09:06:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007267","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__Kidney_EXT","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Grand Challenges award, funded by Cancer Research UK.\n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, head and neck, bladder, gall bladder, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \n\nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Grand Challenges award, funded by Cancer Research UK.\n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, head and neck, bladder, gall bladder, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \n\nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007268","title":"Single-cell multi-omics defines the cell-type specific impact of splicing aberrations in human hematopoietic clonal outgrowths","description":null,"abstract":"RNA splicing factors are recurrently affected by alteration-of-function mutations in clonal blood disorders, highlighting the importance of splicing regulation in hematopoiesis. The main goal of this project was to use a single cell multi-omics approach to investigate and understand the impact that SF3B1 mutations have on the splicing landscape of hematopoetic stem cells and in turn how this leads to human hematopoetic clonal outgrowths.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007269","title":"Whole-genome sequencing of Himalayan populations","description":"Whole-genome sequencing of 60 individuals from 15 Himalayan populations using the Illumina-B HiSeq X platform. These data are part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/.","abstract":"Whole-genome sequencing of 60 individuals from 15 Himalayan populations using the Illumina-B HiSeq X platform. These data are part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-25T09:27:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007270","title":"Patients and HCs CD8 RNA sequencing","description":null,"abstract":"The NFAT family of transcription factors plays central roles in adaptive immunity in murine models, however, their contribution to human immune homeostasis remains poorly defined. In a multigenerational pedigree, we identified three patients carrying germline biallelic missense variants in NFATC1, presenting with recurrent infections, hypogammaglobulinemia and decreased antibody responses. The compound heterozygous NFATC1 variants identified in the patients caused decreased stability and reduced binding of DNA and interacting proteins. We observed defects in early activation and proliferation of T and B cells from these patients, amenable to reconstitution upon genetic rescue. Following stimulation, T-cell activation and proliferation were impaired, reaching that of healthy controls with delay indicative of an adaptive capacity of the cells. Assessment of the metabolic capacity of patient T cells, revealed that NFATc1-dysfunction rendered T cells unable to engage in glycolysis following stimulation, although oxidative metabolic processes were intact. We hypothesized that NFATc1-mutant T cells could compensate for the energy deficit due to defective glycolysis by enhanced lipid metabolism as an adaptation, leading to a delayed, but not lost activation responses. Indeed, we observed increased 13C-labelled palmitate incorporation into citrate indicating higher fatty acid oxidation and we demonstrated that metformin and rosiglitazone improved patient T-cell effector functions. Collectively, enabled by our molecular dissection of NFATC1 mutations and extending the role of NFATc1 in human immunity beyond receptor signaling, and reveal evidence of metabolic plasticity in the context of impaired glycolysis observed in patient T cells to remedy delayed effector responses.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007271","title":"scRNAseq for patients with immunodeficiency and HCs","description":"The NFAT family of transcription factors plays central roles in adaptive immunity in murine models, however, their contribution to human immune homeostasis remains poorly defined. In a multigenerational pedigree, we identified three patients carrying germline biallelic missense variants in NFATC1, presenting with recurrent infections, hypogammaglobulinemia and decreased antibody responses. The compound heterozygous NFATC1 variants identified in the patients caused decreased stability and reduced binding of DNA and interacting proteins. We observed defects in early activation and proliferation of T and B cells from these patients, amenable to reconstitution upon genetic rescue. Following stimulation, T-cell activation and proliferation were impaired, reaching that of healthy controls with delay indicative of an adaptive capacity of the cells. Assessment of the metabolic capacity of patient T cells, revealed that NFATc1-dysfunction rendered T cells unable to engage in glycolysis following stimulation, although oxidative metabolic processes were intact. We hypothesized that NFATc1-mutant T cells could compensate for the energy deficit due to defective glycolysis by enhanced lipid metabolism as an adaptation, leading to a delayed, but not lost activation responses. Indeed, we observed increased 13C-labelled palmitate incorporation into citrate indicating higher fatty acid oxidation and we demonstrated that metformin and rosiglitazone improved patient T-cell effector functions. Collectively, enabled by our molecular dissection of NFATC1 mutations and extending the role of NFATc1 in human immunity beyond receptor signaling, and reveal evidence of metabolic plasticity in the context of impaired glycolysis observed in patient T cells to remedy delayed effector responses.","abstract":"The NFAT family of transcription factors plays central roles in adaptive immunity in murine models, however, their contribution to human immune homeostasis remains poorly defined. In a multigenerational pedigree, we identified three patients carrying germline biallelic missense variants in NFATC1, presenting with recurrent infections, hypogammaglobulinemia and decreased antibody responses. The compound heterozygous NFATC1 variants identified in the patients caused decreased stability and reduced binding of DNA and interacting proteins. We observed defects in early activation and proliferation of T and B cells from these patients, amenable to reconstitution upon genetic rescue. Following stimulation, T-cell activation and proliferation were impaired, reaching that of healthy controls with delay indicative of an adaptive capacity of the cells. Assessment of the metabolic capacity of patient T cells, revealed that NFATc1-dysfunction rendered T cells unable to engage in glycolysis following stimulation, although oxidative metabolic processes were intact. We hypothesized that NFATc1-mutant T cells could compensate for the energy deficit due to defective glycolysis by enhanced lipid metabolism as an adaptation, leading to a delayed, but not lost activation responses. Indeed, we observed increased 13C-labelled palmitate incorporation into citrate indicating higher fatty acid oxidation and we demonstrated that metformin and rosiglitazone improved patient T-cell effector functions. Collectively, enabled by our molecular dissection of NFATC1 mutations and extending the role of NFATc1 in human immunity beyond receptor signaling, and reveal evidence of metabolic plasticity in the context of impaired glycolysis observed in patient T cells to remedy delayed effector responses.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-25T11:55:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007272","title":"Single-cell functional genomics of natural killer cell evasion in blood cancers","description":null,"abstract":"Natural killer (NK) cells are emerging as a promising therapeutic option in cancer. To better understand how cancer cells evade NK cells, we studied interacting NK and blood cancer cells using single-cell and genome-scale functional genomics screens. We combined multiplexed single-cell RNA-sequencing of interacting NK cells and cancer cells, PRISM-based profiling of NK cell sensitivity across a panel of blood cancer cell lines, and genome-scale and single-cell transcriptomics CRISPR screens of cancer-cell intrinsic NK cell resistance mechanisms.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007273","title":"Patients and HCs ATACseq","description":null,"abstract":"The NFAT family of transcription factors plays central roles in adaptive immunity in murine models, however, their contribution to human immune homeostasis remains poorly defined. In a multigenerational pedigree, we identified three patients carrying germline biallelic missense variants in NFATC1, presenting with recurrent infections, hypogammaglobulinemia and decreased antibody responses. The compound heterozygous NFATC1 variants identified in the patients caused decreased stability and reduced binding of DNA and interacting proteins. We observed defects in early activation and proliferation of T and B cells from these patients, amenable to reconstitution upon genetic rescue. Following stimulation, T-cell activation and proliferation were impaired, reaching that of healthy controls with delay indicative of an adaptive capacity of the cells. Assessment of the metabolic capacity of patient T cells, revealed that NFATc1-dysfunction rendered T cells unable to engage in glycolysis following stimulation, although oxidative metabolic processes were intact. We hypothesized that NFATc1-mutant T cells could compensate for the energy deficit due to defective glycolysis by enhanced lipid metabolism as an adaptation, leading to a delayed, but not lost activation responses. Indeed, we observed increased 13C-labelled palmitate incorporation into citrate indicating higher fatty acid oxidation and we demonstrated that metformin and rosiglitazone improved patient T-cell effector functions. Collectively, enabled by our molecular dissection of NFATC1 mutations and extending the role of NFATc1 in human immunity beyond receptor signaling, and reveal evidence of metabolic plasticity in the context of impaired glycolysis observed in patient T cells to remedy delayed effector responses.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007274","title":"DERMATLAS__Cutaneous_gd_T_cell_lymphoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Cutaneous gd T-cell lymphoma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Cutaneous gd T-cell lymphoma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007275","title":"DERMATLAS__Microcystic_adnexal_carcinoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Microcystic adnexal carcinoma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Microcystic adnexal carcinoma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007276","title":"DERMATLAS__Microcystic_adnexal_carcinoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Microcystic adnexal carcinoma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Microcystic adnexal carcinoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007277","title":"DERMATLAS__Microvenular_hemangioma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Microvenular hemangioma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Microvenular hemangioma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007278","title":"DERMATLAS__Microvenular_hemangioma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Microvenular hemangioma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Microvenular hemangioma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007279","title":"DERMATLAS__Spindle_cell_lipoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Spindle cell lipoma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Spindle cell lipoma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007280","title":"DERMATLAS__Spindle_cell_lipoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Spindle cell lipoma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Spindle cell lipoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007281","title":"DERMATLAS__Palisaded_encapsulated_neuroma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Palisaded encapsulated neuroma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Palisaded encapsulated neuroma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007282","title":"DERMATLAS__Palisaded_encapsulated_neuroma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Palisaded encapsulated neuroma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Palisaded encapsulated neuroma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007283","title":"DERMATLAS__Pigmented_spindle_cell_nevus_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Pigmented spindle cell nevus.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Pigmented spindle cell nevus.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007284","title":"DERMATLAS__Pigmented_spindle_cell_nevus_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Pigmented spindle cell nevus.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Pigmented spindle cell nevus.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007285","title":"Sensitive early cancer detection by depleting background cell-free DNA to enrich tumor signals","description":"Methylation of cell-free DNA (cfDNA) is a highly promising feature for non-invasive cancer detection and localization. While current approaches with cfDNA methylation can reliably detect late-stage cancer, early cancer detection is challenging because the fraction of tumor cfDNA in the blood of early-stage cancer patients can be very low, e.g. less than 0.1%. Here we propose the cfDx method to address the above challenges in early cancer detection. cfDx contains a targeted panel and an experimental protocol. The cfDx panel exhaustively contains genome regions consistently hypomethylated in the background cfDNA. By removing the background DNA in those panel regions, tumor or pathological cfDNA in those regions, if any, shall be enriched and stand out. The cfDx method provides the following advantages for cancer detection: (1) Enrich tumor cfDNA, increasing the sensitivity and reducing the sequencing cost. (2) Bypass conversion. To evaluate the cfDx method for early cancer detection, we apply cfDx to cfDNA samples of 614 individuals, including 240 early-stage (I and II) patients with breast, colon, kidney, liver, lung, ovarian, stomach cancer, and 374 individuals without cancer (including patients with various other diseases. The cfDx method demonstrated superior performance in cancer detection and locating. To further evaluate the performance of the conversion-free cfDx method, we developed a cfDx panel targeting the same genomic regions but without the C-&gt;T conversion. We applied the panel to a sub-cohort of 156 patients with the conversion-free cfDx protocol and confirmed that the performance of the cfDx method without conversion is only marginally lower than the one with conversion, opening the possibility of the cfDx method for low-input cfDNA materials. Finally, we demonstrate that with increasing sample sizes, the detection power of our system continues to improve.","abstract":"Methylation of cell-free DNA (cfDNA) is a highly promising feature for non-invasive cancer detection and localization. While current approaches with cfDNA methylation can reliably detect late-stage cancer, early cancer detection is challenging because the fraction of tumor cfDNA in the blood of early-stage cancer patients can be very low, e.g. less than 0.1%. Here we propose the cfDx method to address the above challenges in early cancer detection. cfDx contains a targeted panel and an experimental protocol. The cfDx panel exhaustively contains genome regions consistently hypomethylated in the background cfDNA. By removing the background DNA in those panel regions, tumor or pathological cfDNA in those regions, if any, shall be enriched and stand out. The cfDx method provides the following advantages for cancer detection: (1) Enrich tumor cfDNA, increasing the sensitivity and reducing the sequencing cost. (2) Bypass conversion. To evaluate the cfDx method for early cancer detection, we apply cfDx to cfDNA samples of 614 individuals, including 240 early-stage (I and II) patients with breast, colon, kidney, liver, lung, ovarian, stomach cancer, and 374 individuals without cancer (including patients with various other diseases. The cfDx method demonstrated superior performance in cancer detection and locating. To further evaluate the performance of the conversion-free cfDx method, we developed a cfDx panel targeting the same genomic regions but without the C-&gt;T conversion. We applied the panel to a sub-cohort of 156 patients with the conversion-free cfDx protocol and confirmed that the performance of the cfDx method without conversion is only marginally lower than the one with conversion, opening the possibility of the cfDx method for low-input cfDNA materials. Finally, we demonstrate that with increasing sample sizes, the detection power of our system continues to improve.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007286","title":"Multi-omic analysis of the tumor microenvironment shows clinical correlations in Ph1 study of atezolizumab +/- SoC in MM","description":"Multiple myeloma (MM) remains incurable, and treatment of relapsed/refractory (R/R) disease is challenging. There is an unmet need for more targeted therapies in this setting; deep cellular and molecular phenotyping of the tumor and microenvironment in MM could help guide such therapies. This phase 1b study (NCT02431208) evaluated the safety and efficacy of the anti-programmed death-ligand 1 monoclonal antibody atezolizumab (Atezo) alone or in combination with the standard of care (SoC) treatments lenalidomide (Len) or pomalidomide (Pom) and/or daratumumab (Dara) in patients with R/R MM. Study endpoints included incidence of adverse events (AEs) and overall response rate (ORR). A novel unsupervised integrative multi-omic analysis was performed using RNA sequencing, mass cytometry immunophenotyping, and proteomic profiling of baseline and on-treatment bone marrow samples from patients receiving Atezo monotherapy or Atezo+Dara. A similarity network fusion (SNF) algorithm was applied to preprocessed data. Eighty-five patients were enrolled. Treatment-emergent deaths occurred in 2 patients; both deaths were considered unrelated to study treatment. ORRs ranged from 11.1% (Atezo+Len cohorts, n=18) to 83.3% (Atezo+Dara+Pom cohort, n=6). High-dimensional multi-omic profiling of the tumor microenvironment and integrative SNF analysis revealed novel correlations between cellular and molecular features of the tumor and immune microenvironment, patient selection criteria, and clinical outcome. Atezo monotherapy and SoC combinations were safe in this patient population and demonstrated some evidence of clinical efficacy. Integrative analysis of high dimensional genomics and immune data identified novel clinical correlations that may inform patient selection criteria and outcome assessment in future immunotherapy studies for myeloma.","abstract":"Multiple myeloma (MM) remains incurable, and treatment of relapsed/refractory (R/R) disease is challenging. There is an unmet need for more targeted therapies in this setting; deep cellular and molecular phenotyping of the tumor and microenvironment in MM could help guide such therapies. This phase 1b study (NCT02431208) evaluated the safety and efficacy of the anti-programmed death-ligand 1 monoclonal antibody atezolizumab (Atezo) alone or in combination with the standard of care (SoC) treatments lenalidomide (Len) or pomalidomide (Pom) and/or daratumumab (Dara) in patients with R/R MM. Study endpoints included incidence of adverse events (AEs) and overall response rate (ORR). A novel unsupervised integrative multi-omic analysis was performed using RNA sequencing, mass cytometry immunophenotyping, and proteomic profiling of baseline and on-treatment bone marrow samples from patients receiving Atezo monotherapy or Atezo+Dara. A similarity network fusion (SNF) algorithm was applied to preprocessed data. Eighty-five patients were enrolled. Treatment-emergent deaths occurred in 2 patients; both deaths were considered unrelated to study treatment. ORRs ranged from 11.1% (Atezo+Len cohorts, n=18) to 83.3% (Atezo+Dara+Pom cohort, n=6). High-dimensional multi-omic profiling of the tumor microenvironment and integrative SNF analysis revealed novel correlations between cellular and molecular features of the tumor and immune microenvironment, patient selection criteria, and clinical outcome. Atezo monotherapy and SoC combinations were safe in this patient population and demonstrated some evidence of clinical efficacy. Integrative analysis of high dimensional genomics and immune data identified novel clinical correlations that may inform patient selection criteria and outcome assessment in future immunotherapy studies for myeloma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-26T02:16:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007287","title":"Exome_NanoSeq__Aplastic_anaemia_","description":"The mutational landscape of aplastic anaemia will be characterized using whole exome nanoseq. Samples have been sourced from the Cambridge Biobank.","abstract":"The somatic mutational landscape of aplastic anaemia will be characterized using whole exome nanoseq. Samples have been sourced from the Cambridge Biobank.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007288","title":"Comprehensive single-cell genome analysis at nucleotide resolution using the PTA Analysis Toolbox","description":"We developed a comprehensive bioinformatic workflow, called the PTA Analysis Toolbox (PTATO), to accurately detect single base substitutions, insertions-deletions (indels) and structural variants in PTA-based WGS data. PTATO includes a machine learning approach and filtering based on recurrency to distinguish PTA-artefacts from true mutations with high sensitivity (up to 90%), outperforming existing bioinformatic approaches. Our results show that PTATO enables studying somatic mutagenesis in the genomes of single cells with unprecedented sensitivity and accuracy.","abstract":"We developed a comprehensive bioinformatic workflow, called the PTA Analysis Toolbox (PTATO), to accurately detect single base substitutions, insertions-deletions (indels) and structural variants in PTA-based WGS data. PTATO includes a machine learning approach and filtering based on recurrency to distinguish PTA-artefacts from true mutations with high sensitivity (up to 90%), outperforming existing bioinformatic approaches. Our results show that PTATO enables studying somatic mutagenesis in the genomes of single cells with unprecedented sensitivity and accuracy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-26T09:09:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007289","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__AA_study_urine_TargetedNanoSeq","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, head and neck, bladder, gall bladder, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \n\nThis sub-project will specifically investigate aristolochic exposure in Europe.\n\nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, head and neck, bladder, gall bladder, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Sanger Institute. Non-tumour DNA is also studied for some cancer types. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \n\nThis sub-project will specifically investigate aristolochic exposure in Europe.\n\nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007290","title":"Proteomic Analysis of Non-Muscle Invasive and Muscle Invasive Bladder Cancer Highlights Distinct Subgroups With Metabolic, Matrisomal, and Immune Hallmarks","description":"We present the proteome biology of bladder cancer based on a cohort comprising treatment-naïve non-muscle invasive (NMIBC, N=17) and treatment-naïve muscle-invasive bladder cancer (MIBC, N=51), as well as neoadjuvant-treated MIBC (N=11); using formalin-fixed, paraffin-embedded samples and data-independent acquisition yielding &gt;8,000 protein identifications. The NMIBC proteome reveals two subgroups that represent cell adhesion or lipid metabolism biology. MIBC, compared to NMIBC, shows an altered metabolic proteome together with enrichment of extracellular matrix (ECM), immune response, and complement proteins; in line with three proteomic MIBC subgroups that represent ECM, metabolic, or immune signatures. The ECM and immune subgroups are enriched for markers of M2-like tumor-associated macrophages and dendritic cells, while markers for natural killer cells are exclusive for the ECM subgroup, and markers for cytotoxic T-cells are a hallmark of the immune subgroup. Infiltration of CD8+ PD1+ positive cytotoxic T cells correlated with PD-L1 expression of MIBC, as demonstrated by multiplex immunofluorescence analysis. The metabolic subgroup presents a comparably immune-depleted microenvironment. YAP1 signaling is particularly prominent in the ECM subgroup. The protein BSCL2 emerges as a prognostic marker for MIBC. We highlight increased endogenous proteolysis in MIBC alongside the upregulation of matrix metalloproteases exceeding the upregulation of their endogenous inhibitors. Genomic panel sequencing underlines prevalent FGFR3 mutations in NMIBC and prevalent TP53 mutations in MIBC, but a genomic underpinning of the MIBC subgroups remains elusive. Proteogenomic analysis yields protein-level evidence for more than 1,300 single amino acid variants. The proteomes of neoadjuvant-treated MIBC resembled treatment-naïve MIBC. Tumor-stroma interaction of MIBC was further investigated by proteomic analysis of patient-derived xenografts of MIBC. Our study adds to the proteome-level understanding of bladder cancer.","abstract":"We present the proteome biology of bladder cancer based on a cohort comprising treatment-naïve non-muscle invasive (NMIBC, N=17) and treatment-naïve muscle-invasive bladder cancer (MIBC, N=51), as well as neoadjuvant-treated MIBC (N=11); using formalin-fixed, paraffin-embedded samples and data-independent acquisition yielding &gt;8,000 protein identifications. The NMIBC proteome reveals two subgroups that represent cell adhesion or lipid metabolism biology. MIBC, compared to NMIBC, shows an altered metabolic proteome together with enrichment of extracellular matrix (ECM), immune response, and complement proteins; in line with three proteomic MIBC subgroups that represent ECM, metabolic, or immune signatures. The ECM and immune subgroups are enriched for markers of M2-like tumor-associated macrophages and dendritic cells, while markers for natural killer cells are exclusive for the ECM subgroup, and markers for cytotoxic T-cells are a hallmark of the immune subgroup. Infiltration of CD8+ PD1+ positive cytotoxic T cells correlated with PD-L1 expression of MIBC, as demonstrated by multiplex immunofluorescence analysis. The metabolic subgroup presents a comparably immune-depleted microenvironment. YAP1 signaling is particularly prominent in the ECM subgroup. The protein BSCL2 emerges as a prognostic marker for MIBC. We highlight increased endogenous proteolysis in MIBC alongside the upregulation of matrix metalloproteases exceeding the upregulation of their endogenous inhibitors. Genomic panel sequencing underlines prevalent FGFR3 mutations in NMIBC and prevalent TP53 mutations in MIBC, but a genomic underpinning of the MIBC subgroups remains elusive. Proteogenomic analysis yields protein-level evidence for more than 1,300 single amino acid variants. The proteomes of neoadjuvant-treated MIBC resembled treatment-naïve MIBC. Tumor-stroma interaction of MIBC was further investigated by proteomic analysis of patient-derived xenografts of MIBC. Our study adds to the proteome-level understanding of bladder cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-26T11:28:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007291","title":"Elucidating the heterogeneity of immunotherapy response and immune-related toxicities by longitudinal ctDNA and immune cell compartment tracking in lung cancer","description":null,"abstract":"Purpose: Although immunotherapy is the mainstay of therapy for advanced non-small cell lung cancer (NSCLC), robust biomarkers of clinical response are lacking. The heterogeneity of clinical responses together with the limited value of radiographic response assessments to timely and accurately predict therapeutic effect -especially in the setting of stable disease- call for the development of molecularly-informed real-time minimally invasive predictive biomarkers. In addition to capturing tumor regression, liquid biopsies may be informative in evaluating immune-related adverse events (irAEs).\nExperimental design: We investigated longitudinal changes in circulating tumor DNA (ctDNA) in patients with metastatic NSCLC who received immunotherapy-based regimens. Using ctDNA targeted error-correction sequencing together with matched sequencing of white blood cells and tumor tissue, we tracked serial changes in cell-free tumor load (cfTL) and determined molecular response for each patient. Peripheral T-cell repertoire dynamics were serially assessed and evaluated together with plasma protein expression profiles.\nResults: Molecular response, defined as complete clearance of cfTL, was significantly associated with progression-free (log-rank p=0.0003) and overall survival (log-rank p=0.01) and was particularly informative in capturing differential survival outcomes among patients with radiographically stable disease. For patients who developed irAEs, peripheral blood T-cell repertoire reshaping, assessed by significant TCR clonotypic expansions and regressions were noted on-treatment.\nConclusions: Molecular responses assist with interpretation of heterogeneous clinical responses especially for patients with stable disease. Our complementary assessment of the tumor and immune compartments by liquid biopsies provides an approach for monitoring of clinical benefit and immune-related toxicities for patients with NSCLC receiving immunotherapy.\nStatement of translational relevance: Longitudinal dynamic changes in cell-free tumor load and reshaping of the peripheral T-cell repertoire capture clinical outcomes and immune-related toxicities during immunotherapy for patients with non-small cell lung cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-26T19:21:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007292","title":"The genomic landscape of recurrent ovarian high grade serous carcinoma: the BriTROC-1 study","description":"The BriTROC-1 study, spanning 15 centres across the United Kingdom, is a prospective observational project investigating putative causes of relapse in high-grade serous carcinoma (HGSC). Potential genomic changes associated with disease recurrence are examined by studying paired tumour samples collected from patients at diagnosis and after relapse after receiving platinum based chemotherapy. Shallow whole genome sequencing and targeted amplicon sequencing are used to identify copy number aberrations and short variants respectively.","abstract":"The BriTROC-1 study, spanning 15 centres across the United Kingdom, is a prospective observational project investigating putative causes of relapse in high-grade serous carcinoma (HGSC). Potential genomic changes associated with disease recurrence are examined by studying paired tumour samples collected from patients at diagnosis and after relapse after receiving platinum based chemotherapy. Shallow whole genome sequencing and targeted amplicon sequencing are used to identify copy number aberrations and short variants respectively.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-27T18:23:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007293","title":"GWAS on covid-19 severity and susceptibility in the province of Bergamo, Italy","description":"This is a case-control GWAS that involved the voluntary recruitment of inhabitants of the Bergamo province via an online questionnaire. We collected detailed clinical data and verified all information through personal interviews. Cases (severe COVID-19; G1) and controls (mild or asymptomatic COVID-19, G2; non-infected, G3) were matched by age, sex and risk factors","abstract":"This is a case-control GWAS that involved the voluntary recruitment of inhabitants of the Bergamo province via an online questionnaire. We collected detailed clinical data and verified all information through personal interviews. Cases (severe COVID-19; G1) and controls (mild or asymptomatic COVID-19, G2; non-infected, G3) were matched by age, sex and risk factors","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007294","title":"Genomics-based characterization and personalized treatment in pleural and peritoneal mesothelioma","description":null,"abstract":"Malignant mesothelioma is a rare and aggressive tumor originating in 80% of cases from pleura (malignant pleural mesothelioma, MPM) and in 10% from peritoneum (malignant peritoneal mesothelioma, MPeM). Our cohort comprised patients with MPM and MPeM that were enrolled in MASTER (HIPO_021), a prospective precision oncology registry trial conducted by the National Center for Tumor Diseases (NCT) Heidelberg/Dresden and the German Cancer Consortium (DKTK) addressing adults with rare advanced-stage cancer across histologies. We performed WGS, WES, transcriptome analysis, and germline analysis. Results informed a dedicated molecular tumor board (MTB) leading to therapy recommendations. Progression-free survival of the first treatment according to an MTB recommendation (PFS2) was compared to the last prior systemic treatment (PFS1) in each patient (PFSratio). Mutated genes (SNVs, InDels, fusions, homozygous deletions) in more than 3 patients listed in COSMIC’s Cancer Gene Census were BAP1, NF2, PBRM1, ARID2, SETD2, B2M, SETDB1, DDX3X and TP53. Signs of defective homologous recombination were detected in most patients. Our findings suggest efficacy of personalized therapies in MPM/MPeM. They underscore the need for further clinical investigation into HR deficiency in MPM/MPeM beyond BAP1 alterations.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-04-11T09:12:29.549464+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007295","title":"Exploration of neuroblastoma xenograft models for tumor extracellular RNA profiling in murine blood plasma","description":null,"abstract":"Minimally invasive liquid biopsies are becoming increasingly important in the diagnosis and treatment follow-up of cancer patients, including children with neuroblastoma. Such biopsies contain various biomarker types, including extracellular RNA (exRNA) that has the potential to reflect dynamic changes in the tumor. However, for this type of biomarker, it is challenging to distinguish tumor-derived from normal signals. To overcome this limitation, xenograft models serve as a practical tool. In a mouse engrafted with human tumor cells, human exRNA is by definition originating from the tumor, whereas murine exRNA is host-derived. To study treatment response by monitoring tumor-derived exRNA, xenograft models with a high release of tumor exRNA into the circulation are desirable. However, it remains unclear which factors determine this release. The aim of this study was to evaluate whether and to what extent the cell line, its engraftment site, or the tumor size influence the amount of tumoral exRNA detected in blood plasma. To that end, four different neuroblastoma cell lines were engrafted in immunocompromised mice. Grafts were performed subcutaneously in the flank or orthotopically in the adrenal gland. Tumor sizes were monitored by caliper measurements (subcutaneous grafts), or MRI scans (orthotopic grafts) and blood was collected via terminal cardiac puncture to evaluate the tumoral exRNA fraction. We demonstrate that tumoral exRNA levels are highly dependent on the cell line used. Also, the volume of subcutaneous tumor grafts is an important factor, with 1000 mm3 as a minimal size for sufficient release. Orthotopic engraftment potentially results in superior levels of tumoral exRNA. These factors should therefore be carefully considered when performing experiments to study circulating RNA biomarkers.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-30T13:43:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007296","title":"Human data for chromatin accessibility (ATAC-Seq and scATAC-Seq) and transcriptome (RNA-Seq and scRNA-Seq) in eight B-cell precursors, from HSC to Naive B cells","description":"We generated paired transcriptomic (RNA-Seq) and chromatin accessibility (ATAC-Seq) profiles from 8 immune cell populations representing the early lymphoid hematopoietic differentiation stages along the B cell lineage: HSC, CLP, pro-B, pre-B, Immature B, Transitional B, Naive B CD5-, Naive B CD5+. Cell populations were isolated from healthy adult human bone marrow precursors and peripheral blood (n=13) following a predefined sorting strategy. For each donor, a subset of different cell type populations was obtained. \nAdditionally, to explore the continuous dynamic of RNA and ATAC, we generated a single-cell sample of human CD34+ B cell precursors.","abstract":"We generated paired transcriptomic (RNA-Seq) and chromatin accessibility (ATAC-Seq) profiles from 8 immune cell populations representing the early lymphoid hematopoietic differentiation stages along the B cell lineage: HSC, CLP, pro-B, pre-B, Immature B, Transitional B, Naive B CD5-, Naive B CD5+. Cell populations were isolated from healthy adult human bone marrow precursors and peripheral blood (n=13) following a predefined sorting strategy. For each donor, a subset of different cell type populations was obtained. \nAdditionally, to explore the continuous dynamic of RNA and ATAC, we generated a single-cell sample of human CD34+ B cell precursors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-30T14:30:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007297","title":"Clinical outcomes and immune correlates of response to nivolumab plus chemoradiotherapy in women with locally-advanced cervical cancer – NiCOL study","description":"Concurrent chemoradiotherapy (CRT) with blockade of the PD-1 pathway may enhance immune-mediated tumor control through increased phagocytosis, cell death, and antigen presentation. The NiCOL phase 1 trial was designed to determine safety, tolerance, and immune correlates of response to the PD-1 blocking antibody, nivolumab, with and following concurrent CRT in 16 women with locally advanced cervical cancer (LACC). Three patients experienced grade 3 dose-limiting toxicities. The overall response rate was 93.8% [95%CI: 69.8%-99.8%] with a 2-year PFS of 75% [95% CI: 56.5%-99.5%]. Compared to patients with progressive disease (PD), progression-free (PF) subjects showed a brisker stromal immune infiltrate, higher proximity of tumor-infiltrating CD3+ T cells to PD-L1+ tumor cells and of Foxp3+ T cells to proliferating CD11c+ myeloid cells. PF had higher baseline levels of PD-1 on EMRA CD4+ T cells and ICOS-L on tumor-associated macrophages (TAMs) vs PD, which instead displayed enhanced PD-L1 expression on TAMs and higher, circulating frequencies of proliferating Tregs at baseline. Concomitant nivolumab plus definitive CRT is safe and associated with encouraging PFS rates. Further validation in the subset of LACC displaying pre-existing, adaptive immune activation is warranted.","abstract":"Concurrent chemoradiotherapy (CRT) with blockade of the PD-1 pathway may enhance immune-mediated tumor control through increased phagocytosis, cell death, and antigen presentation. The NiCOL phase 1 trial was designed to determine safety, tolerance, and immune correlates of response to the PD-1 blocking antibody, nivolumab, with and following concurrent CRT in 16 women with locally advanced cervical cancer (LACC). Three patients experienced grade 3 dose-limiting toxicities. The overall response rate was 93.8% [95%CI: 69.8%-99.8%] with a 2-year PFS of 75% [95% CI: 56.5%-99.5%]. Compared to patients with progressive disease (PD), progression-free (PF) subjects showed a brisker stromal immune infiltrate, higher proximity of tumor-infiltrating CD3+ T cells to PD-L1+ tumor cells and of Foxp3+ T cells to proliferating CD11c+ myeloid cells. PF had higher baseline levels of PD-1 on EMRA CD4+ T cells and ICOS-L on tumor-associated macrophages (TAMs) vs PD, which instead displayed enhanced PD-L1 expression on TAMs and higher, circulating frequencies of proliferating Tregs at baseline. Concomitant nivolumab plus definitive CRT is safe and associated with encouraging PFS rates. Further validation in the subset of LACC displaying pre-existing, adaptive immune activation is warranted.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-30T14:37:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007298","title":"Early ctDNA molecular response captures therapeutic response in the first stage of CCTG BR.36 ctDNA-directed, multi-center phase II study of molecular response adaptive immunotherapy in non-small cell lung cancer","description":null,"abstract":"Circulating tumor DNA (ctDNA) has shown promise in capturing primary resistance to immunotherapy. BR.36 is a multi-center, randomized, ctDNA-directed, phase II trial of molecular response-adaptive immuno-chemotherapy for patients with lung cancer (NCT04093167). Consisting of 2 independent stages, the primary objectives of stage 1 were to ascertain ctDNA response, determine optimal timing and concordance with radiologic RECIST response. Liquid biopsy analyses utilized a validated tumor-agnostic white blood cell DNA-informed next-generation sequencing approach. Maximal mutant allele fraction clearance on C3D1 signified molecular response (mR).  The trial met its primary endpoint, with a sensitivity of ctDNA response for RECIST response of 82% (90% CI:52%-97%) and a specificity of 75% (90% CI:56.5%-88.5%). Median time to ctDNA response was 2.1 months (90% CI:1.5-2.6) and patients with mR attained longer progression-free (5.03 vs 2.6 months) and overall survival (not reached vs 7.23 months). These findings are incorporated into the ctDNA-interventional randomized second stage of the trial.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-30T19:24:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007299","title":"Circulating tumor DNA, pathological and immunologic responses to neoadjuvant nivolumab or nivolumab plus relatlimab and chemoradiotherapy in resectable esophageal/gastroesophageal junction cancer","description":null,"abstract":"Gastroesophageal tumor kinetics during immune checkpoint inhibition (ICI) remain poorly understood. We report a phase II trial that evaluated neoadjuvant nivolumab (arm A) or nivolumab-relatlimab (arm B) in combination with chemoradiotherapy in 32 patients with resectable gastroesophageal cancer together with an in-depth evaluation of pathological, molecular and functional immune responses (NCT03044613). Patients with undetectable circulating tumor DNA (ctDNA) post-ICI induction, pre- and post-operatively had a significantly longer RFS and OS. Cell-free tumor load contraction was reflective of neoantigen-specific T-cell responses. Our findings highlight tumor kinetics during ICI that may open a therapeutic window for future intervention.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-30T19:34:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007300","title":"RNAseq of Colorectal cancer organoid-stroma biobank cohort","description":"In colorectal cancers (CRC) the tumor microenvironment plays a key role for prognosis and therapy efficacy. Patient-derived tumor organoids (PDTOs) show enormous potential for preclinical testing, however, in purely epithelial cultures features including the ‘consensus molecular subtypes’ (CMS) are largely eradicated. To better reflect cell heterogeneity, we established the CRC organoid-stroma biobank of matched PDTOs and cancer-associated fibroblasts (CAFs) from 30 patients. Context-specific phenotyping showed that xenotransplantation or co-culture with CAFs restores the individual transcriptomic status and instructs subtype-specific stromal gene expression. Furthermore, co-culture exposed CMS4-specific resistance to Gefitinib and SN-38 and revealed prognostic gene expression signatures. Chemogenomic library screening identified patient- and therapy-dependent mechanisms of stromal resistance including MET as common target. Our results demonstrate that CRC phenotypes are encrypted in the cancer epithelium in a plastic fashion that strongly depends on the context. Consequently, CAFs are essential for faithful representation of molecular subtypes and therapy responses ex vivo.","abstract":"In colorectal cancers (CRC) the tumor microenvironment plays a key role for prognosis and therapy efficacy. Patient-derived tumor organoids (PDTOs) show enormous potential for preclinical testing, however, in purely epithelial cultures features including the ‘consensus molecular subtypes’ (CMS) are largely eradicated. To better reflect cell heterogeneity, we established the CRC organoid-stroma biobank of matched PDTOs and cancer-associated fibroblasts (CAFs) from 30 patients. Context-specific phenotyping showed that xenotransplantation or co-culture with CAFs restores the individual transcriptomic status and instructs subtype-specific stromal gene expression. Furthermore, co-culture exposed CMS4-specific resistance to Gefitinib and SN-38 and revealed prognostic gene expression signatures. Chemogenomic library screening identified patient- and therapy-dependent mechanisms of stromal resistance including MET as common target. Our results demonstrate that CRC phenotypes are encrypted in the cancer epithelium in a plastic fashion that strongly depends on the context. Consequently, CAFs are essential for faithful representation of molecular subtypes and therapy responses ex vivo.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-30T20:36:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007301","title":"WES of Colorectal cancer organoid-stroma biobank cohort","description":"In colorectal cancers (CRC) the tumor microenvironment plays a key role for prognosis and therapy efficacy. Patient-derived tumor organoids (PDTOs) show enormous potential for preclinical testing, however, in purely epithelial cultures features including the ‘consensus molecular subtypes’ (CMS) are largely eradicated. To better reflect cell heterogeneity, we established the CRC organoid-stroma biobank of matched PDTOs and cancer-associated fibroblasts (CAFs) from 30 patients. Context-specific phenotyping showed that xenotransplantation or co-culture with CAFs restores the individual transcriptomic status and instructs subtype-specific stromal gene expression. Furthermore, co-culture exposed CMS4-specific resistance to Gefitinib and SN-38 and revealed prognostic gene expression signatures. Chemogenomic library screening identified patient- and therapy-dependent mechanisms of stromal resistance including MET as common target. Our results demonstrate that CRC phenotypes are encrypted in the cancer epithelium in a plastic fashion that strongly depends on the context. Consequently, CAFs are essential for faithful representation of molecular subtypes and therapy responses ex vivo.","abstract":"In colorectal cancers (CRC) the tumor microenvironment plays a key role for prognosis and therapy efficacy. Patient-derived tumor organoids (PDTOs) show enormous potential for preclinical testing, however, in purely epithelial cultures features including the ‘consensus molecular subtypes’ (CMS) are largely eradicated. To better reflect cell heterogeneity, we established the CRC organoid-stroma biobank of matched PDTOs and cancer-associated fibroblasts (CAFs) from 30 patients. Context-specific phenotyping showed that xenotransplantation or co-culture with CAFs restores the individual transcriptomic status and instructs subtype-specific stromal gene expression. Furthermore, co-culture exposed CMS4-specific resistance to Gefitinib and SN-38 and revealed prognostic gene expression signatures. Chemogenomic library screening identified patient- and therapy-dependent mechanisms of stromal resistance including MET as common target. Our results demonstrate that CRC phenotypes are encrypted in the cancer epithelium in a plastic fashion that strongly depends on the context. Consequently, CAFs are essential for faithful representation of molecular subtypes and therapy responses ex vivo.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-30T20:36:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007302","title":"Baseline RNAseq analysis of POETIC Good/Poor Responders to aromatase inhibitors based on change in Ki67","description":null,"abstract":"Using RNAseq, we compare the 15% of poorest responders (PRs, n=177) as measured by proportional Ki67 changes after 2 weeks of neoadjuvant aromatase inhibitors to good responders (GRs, n=190) selected from the top 50% responders in the POETIC trial and matched for baseline Ki67 categories. In the POETIC trial, 4,480 postmenopausal women with primary ER+ BC were randomised 2:1 to receive either treatment with a non-steroidal AI (letrozole or anastrozole) for 2 weeks before and 2 weeks after surgery or to no perisurgical treatment. Only AI-treated patients with HER2- tumors, paired baseline and surgery Ki67 available, and baseline Ki67 immunohistochemistry (IHC) &gt;10% (to minimise imprecision in proportional Ki67 falls) were included for selection. Data is baseline RNAseq analysis of POETIC Good/Poor Responders to aromatase inhibitors based on change in Ki67.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-31T08:36:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007303","title":"Targeted exome DNA sequencing analysis of POETIC Good/Poor Responders to aromatase inhibitors based on change in Ki67","description":null,"abstract":"Using RNAseq, we compare the 15% of poorest responders (PRs, n=177) as measured by proportional Ki67 changes after 2 weeks of neoadjuvant aromatase inhibitors to good responders (GRs, n=190) selected from the top 50% responders in the POETIC trial and matched for baseline Ki67 categories. In the POETIC trial, 4,480 postmenopausal women with primary ER+ BC were randomised 2:1 to receive either treatment with a non-steroidal AI (letrozole or anastrozole) for 2 weeks before and 2 weeks after surgery or to no perisurgical treatment. Only AI-treated patients with HER2- tumors, paired baseline and surgery Ki67 available, and baseline Ki67 immunohistochemistry (IHC) &gt;10% (to minimise imprecision in proportional Ki67 falls) were included for selection. Data is targeted exome DNA sequencing analysis of POETIC Good/Poor Responders to aromatase inhibitors based on change in Ki67.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-31T08:36:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007304","title":"Transcriptomic analysis of the three monocytic subsets in health and SLE","description":"We performed mRNA sequencing in the three monocytic subpopulations being the CD14+CD16- classical monocytes, CD14+CD16+ intermediate monocytes and CD14-CD16+ non-classical monocytes from 7 SLE patients with high disease activity (SLEDAI≥8 or PGA&gt;1.5) and 8 age-sex matched healthy individuals (HI) (45 samples sequenced in total). Differential expression analysis and GSEA were performed in order to characterize the transcriptome profile and the disease-specific signatures of each monocytic subset in SLE.","abstract":"We performed mRNA sequencing in the three monocytic subpopulations being the CD14+CD16- classical monocytes, CD14+CD16+ intermediate monocytes and CD14-CD16+ non-classical monocytes from 7 SLE patients with high disease activity (SLEDAI≥8 or PGA&gt;1.5) and 8 age-sex matched healthy individuals (HI) (45 samples sequenced in total). Differential expression analysis and GSEA were performed in order to characterize the transcriptome profile and the disease-specific signatures of each monocytic subset in SLE.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007305","title":"Healthy human B-lymphopoiesis RNA-Seq reference using FACS sorted bone marrow aspirates","description":null,"abstract":"To define a transcriptomic reference of human B lymphopoiesis, bone marrow aspirates were obtained from n=4 healthy donors (study registration DRKS00023583). After immunodensity cell separation, samples were FACS-sorted into 7 established lymphopoietic differentiation stages. RNA was extracted from 5,000-320,000 cells per differentiation stage and subjected to ultra-low-input RNA sequencing after generation of stranded sequencing libraries.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-31T14:14:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007306","title":"Machine learning guided signal enrichment for ultrasensitive plasma tumor burden monitoring","description":"Development of a novel machine learning guided ctDNA detection platform for use in liquid biopsy detection and therapeutic monitoring of solid tumors in several clinical contexts. Included are WGS alignments from our study.","abstract":"Development of a novel machine learning guided ctDNA detection platform for use in liquid biopsy detection and therapeutic monitoring of solid tumors in several clinical contexts. Included are WGS alignments from our study.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-05-31T15:34:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007307","title":"Human subsistence and signatures of selection on chemosensory genes","description":null,"abstract":"Chemosensation (olfaction, taste) is essential for detecting and assessing foods, such that dietary shifts elicit evolutionary changes in vertebrate chemosensory genes. The transition from hunting and gathering to agriculture dramatically altered how humans acquire food. Recent genetic and linguistic studies suggest agriculture may have precipitated olfactory degeneration. Here, we explore the effects of subsistence behaviors on olfactory (OR) and taste (TASR) receptor genes among rainforest foragers and neighboring agriculturalists in Africa and Southeast Asia. We analyze 378 functional OR and 26 functional TASR genes in 133 individuals across populations in Uganda (Twa, Sua, BaKiga) and the Philippines (Agta, Mamanwa, Manobo) with differing subsistence histories. We find no evidence of relaxed selection on chemosensory genes in agricultural populations. However, we identify subsistence-related signatures of local adaptation on chemosensory genes within each geographic region. Our results highlight the importance of culture, subsistence economy, and drift in human chemosensory perception.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-01T08:52:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007308","title":"Cell-free DNA sequencing data of healthy control, atrophic gastritis, and gastric cancer patients’ blood","description":null,"abstract":"In this study, cell-free DNA sequencing is performed to obtain a personalized genetic profile of cell-free DNA during the course of gastric cancer. The study involves control, premalignant (atrophic gastritis), and malignant gastric cancer cases. Detected variant alleles and determined fractions during the course of a disease, will show the possible application of cfDNA as a minimally-invasive biomarker for not only early gastric cancer diagnostics but also for disease state monitoring.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-02T21:20:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007309","title":"Therapeutic vulnerabilities in CCA from different etiologies identified using integrative multi-omics enhancer activity profiling","description":null,"abstract":"Through integrative analysis of enhancer and transcriptomic landscapes of CCA from diverse populations, we identified 3 distinct groups, associated with different etiologies, that were enriched in unique pathways. The first group (ESTRO) displayed aberrant enhancer activation in estrogen signaling, and were comprised of mostly fluke-associated CCAs. Another group (OXPHO) displayed activated oxidative phosphorylation pathways, and were associated with hypermethylated BAP1 and IDH-mutant CCAs. Immune-related pathways were activated in the final group (IMMUN), made up of an immunogenic CCA subtype as well as CCA with aristolochic acid mutational signatures. Drug inhibitors of identified enriched pathways reduced tumor growth in in vitro and in vivo models.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-03T09:05:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007310","title":"GWAS on covid-19 severity and susceptibility in the province of Bergamo, Italy","description":"This is a case-control GWAS that involved the voluntary recruitment of inhabitants of the Bergamo province via an online questionnaire. We collected detailed clinical data and verified all information through personal interviews. Cases (severe COVID-19; G1) and controls (mild or asymptomatic COVID-19, G2; non-infected, G3) were matched by age, sex and risk factors","abstract":"This is a case-control GWAS that involved the voluntary recruitment of inhabitants of the Bergamo province via an online questionnaire. We collected detailed clinical data and verified all information through personal interviews. Cases (severe COVID-19; G1) and controls (mild or asymptomatic COVID-19, G2; non-infected, G3) were matched by age, sex and risk factors","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-05T14:21:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007311","title":"Multi-omic analysis of myxopapillary ependymomas","description":null,"abstract":"Ependymomas (EPTs) are tumors of the central nervous system (CNS) that occur in both children and adults. DNA methylation profiling has identified 9 ependymoma subtypes, 3 subtypes in each of the 3 regions of the CNS were EPTs occur (the spine, posterior fossa and supratentorial). However, only two of the supratentorial subgroups have been found to have recurrent somatic mutation with fusions involving RELA or YAP1. We used RNA-Seq and linked-read sequencing to determine whether we could identify any structural variants or resulting fusions missed by array-based technologies in spinal myxopapillary ependymomas (MPEs). We detected extensive copy number variants in the MPEs, but no somatic structural variants. Using the RNA-Seq, we discovered a recurrent NEDD1 fusion in the MPEs which was not found to be exclusive to this subtype.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007312","title":"MAVE_SGE_v0_3_1","description":"New study to reflect change in protocol following on from study 7135","abstract":"To define the function of every nucleotide and all genetic variants in human and other genomes at scale","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007313","title":"ExHiBITT shows that microbiome from colon biopsies, caecal fluid from colonoscopies and faecal samples shape different microbiome-host interactions","description":"The objective of the colonoscopy study is to carry out the 16s sequencing of colon biopsies and faecal samples provided in ExHiBITT study to compare potential fluctuations in the microbiota of different sites.","abstract":"The objective of the colonoscopy study is to carry out the 16s sequencing of colon biopsies and faecal samples provided in ExHiBITT study to compare potential fluctuations in the microbiota of different sites.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-06T10:01:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007314","title":"Investigation of different library preparation and tissue of origin deconvolution methods for urine and plasma cfDNA methylome analysis","description":"In this study, a single- and a double-stranded library preparation approach was evaluated with respect to their technical biases when applied on cfDNA from plasma and urine. This study thus outlines potential limitations of double-stranded library preparation for methylation analysis of cfDNA especially for urinary cfDNA. While the double-stranded method allows jagged end analysis in addition to TOO analysis, it leads to significant methylation bias in urinary cfDNA, which single-stranded methods can overcome.","abstract":"In this study, a single- and a double-stranded library preparation approach was evaluated with respect to their technical biases when applied on cfDNA from plasma and urine. This study thus outlines potential limitations of double-stranded library preparation for methylation analysis of cfDNA especially for urinary cfDNA. While the double-stranded method allows jagged end analysis in addition to TOO analysis, it leads to significant methylation bias in urinary cfDNA, which single-stranded methods can overcome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-06T12:38:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007315","title":"Langerhan_cell_histiocytosis_WGS","description":"The somatic mutational landscape of langerhan cell histiocytosis will be characterized using WGS.","abstract":"The somatic mutational landscape of of langerhan cell histiocytosis will be characterized using EMSEQ. Samples have been sourced from Newcastle University.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007316","title":"Exome_NanoSeq__Buccals_","description":"Exome NanoSeq in buccal swab samples obtained from patients with a wide range of clinical phenotypes.","abstract":"Investigating the driver landscape in buccals cells, in both health and disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-06T15:25:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007317","title":"Single-cell RNA-sequencing of CD34+ bone marrow cells from patients with SLE, healthy individuals and umbilical cord blood samples","description":"All immune cells that contribute to the pathogenesis of systemic lupus erythematosus (SLE) derive from adult haematopoietic stem and progenitor cells (HSPCs) within the bone marrow (BM). We reasoned that the fundamental abnormalities in the disease can be traced back to HSPCs. The aim of this study was to delineate human haematopoietic CD34+ progenitor subpopulations and to identify deregulated pathways in each subpopulation in SLE as compared to healthy controls and umbilical cord blood samples. This study revealed both quantitative-as evidenced by decreased numbers of non-proliferating early progenitors and qualitative differences- characterized by an IFN signature, which is known to drive loss of function and depletion of HSPCs.","abstract":"All immune cells that contribute to the pathogenesis of systemic lupus erythematosus (SLE) derive from adult haematopoietic stem and progenitor cells (HSPCs) within the bone marrow (BM). We reasoned that the fundamental abnormalities in the disease can be traced back to HSPCs. The aim of this study was to delineate human haematopoietic CD34+ progenitor subpopulations and to identify deregulated pathways in each subpopulation in SLE as compared to healthy controls and umbilical cord blood samples. This study revealed both quantitative-as evidenced by decreased numbers of non-proliferating early progenitors and qualitative differences- characterized by an IFN signature, which is known to drive loss of function and depletion of HSPCs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-07T07:26:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007318","title":"Multiomics analyses of ALS prefrontal cortex tissue","description":null,"abstract":"We performed a multiomic analysis of the prefrontal cortex from 51 sporadic ALS patients and 50 control subjects, aiming to characterize early disease mechanisms in ALS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-05-06T12:10:03.456196+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007319","title":"Understanding_splicing_using_deep_mutational_scanning","description":"Deep mutational scanning experiments to investigate the effect of mutations (substitutions, indels) on alternative splicing to gain insight in splicing regulatory sequences, to improve variant splicing variants classification and antisense oligonucleotide design.","abstract":"Deep mutational scanning experiments to investigate the effect of mutations (substitutions, indels) on alternative splicing to gain insight in splicing regulatory sequences, to improve variant splicing variants classification and antisense oligonucleotide design.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007320","title":"Langerhan_cell_histiocytosis_EMseq","description":"The somatic mutational landscape of langerhan cell histiocytosis will be characterized using EMseq","abstract":"The somatic mutational landscape of of langerhan cell histiocytosis will be characterized using EMSEQ. Samples have been sourced from Newcastle University.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007321","title":"Possible DNA damage after paternal exposure to ionizing radiation in radar technicians","description":"Effects of accidental and prolonged radiation exposure on the human germline remain a topic of medical interest. Transgenerational signatures of ionizing radiation exposure are primarily implicated to be clustered de-novo mutations (cDNMs, multiple de-novo mutations within 20bp). We sequenced the whole genome of 110 children from 70 families (Radar cohort). The father in this cohort were exposed to 0-353mSv of ionizing radiation and serve as exposed samples.","abstract":"Effects of accidental and prolonged radiation exposure on the human germline remain a topic of medical interest. Transgenerational signatures of ionizing radiation exposure are primarily implicated to be clustered de-novo mutations (cDNMs, multiple de-novo mutations within 20bp). We sequenced the whole genome of 110 children from 70 families (Radar cohort). The father in this cohort were exposed to 0-353mSv of ionizing radiation and serve as exposed samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-07T12:12:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007322","title":"Plate_based_gDNA_sequencing_of_human_cells_using_transposase_based_methods","description":"This study aims to develop a new single cell genomics method similar to duplex sequencing (such as the Nanoseq method used in CASM). It is a plate based and uses Tn5 transposase. We are setting up test libraries from single cells derived from single cell colonies and primary cells.","abstract":"CASM is currently leading the emerging field of somatic mutation in normal tissues, which has led to exciting discoveries and multiple high-impact publications in the past few years. This is the result of a considerable investment in R&amp;D, which led to the establishment of the duplex sequencing (Nanoseq). In this protocol we aim to develop a new single cell DNA sequencing method with nano basepair error rate similar to duplex sequencing  methods.\n\nSingle cell DNA duplex sequencing will dramatically improve our ability to detect causal mutations and lead to discovery of novel pathways that derive disease progression and tumorigenesis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007323","title":"A longitudinal single-cell atlas of treatment response in pediatric AML","description":"Pediatric acute myeloid leukemia (pAML) is a disease characterized by heterogeneous cellular composition, driver alterations and prognosis. Characterization of this heterogeneity and how it affects treatment response remains relatively understudied in pediatric patients. We therefore used single-cell RNA sequencing and single-cell ATAC sequencing to profile 684,031 diagnosis, remission and relapse cells from 28 patients representing different pAML subtypes. Analysis revealed that at diagnosis, cellular compositions differed between distinct subgroups. Upon relapse, cellular hierarchies transitioned towards a more primitive state regardless of subtype. These primitive cells were distinct compared to cells at diagnosis, having underrepresentation of transcriptional programs involved in myeloid differentiation while programs commonly found in other lineages were overrepresented. In a subset of patients, this appeared to accompany the appearance of a B-lymphoid-like hierarchy. Together, our data reveal the emergence of apparent subtype-specific plasticity upon treatment and inform on potential novel therapeutic angles to target these cell populations.","abstract":"Pediatric acute myeloid leukemia (pAML) is a disease characterized by heterogeneous cellular composition, driver alterations and prognosis. Characterization of this heterogeneity and how it affects treatment response remains relatively understudied in pediatric patients. We therefore used single-cell RNA sequencing and single-cell ATAC sequencing to profile 684,031 diagnosis, remission and relapse cells from 28 patients representing different pAML subtypes. Analysis revealed that at diagnosis, cellular compositions differed between distinct subgroups. Upon relapse, cellular hierarchies transitioned towards a more primitive state regardless of subtype. These primitive cells were distinct compared to cells at diagnosis, having underrepresentation of transcriptional programs involved in myeloid differentiation while programs commonly found in other lineages were overrepresented. In a subset of patients, this appeared to accompany the appearance of a B-lymphoid-like hierarchy. Together, our data reveal the emergence of apparent subtype-specific plasticity upon treatment and inform on potential novel therapeutic angles to target these cell populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-07T20:44:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007324","title":"Analysis of Loose Ends in Cancer Genome Structure","description":"Short-read sequencing (SRS) forms the basis of our understanding of cancer genome evolution, yet it is widely thought to be inadequate for detecting structural variants (SVs). To understand the nature of cancer SVs missed by SRS, we introduce the concept of \"loose ends\" - sites of missing rearrangements revealed by balancing copy number (CN) across the genomic intervals and adjacencies of a genome graph.","abstract":"Short-read sequencing (SRS) forms the basis of our understanding of cancer genome evolution, yet it is widely thought to be inadequate for detecting structural variants (SVs). To understand the nature of cancer SVs missed by SRS, we introduce the concept of \"loose ends\" - sites of missing rearrangements revealed by balancing copy number (CN) across the genomic intervals and adjacencies of a genome graph.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-07T22:46:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007325","title":"Targeted_NanoSeq__Chromosomal_Instability_Syndromes_","description":"Chromosome instability syndromes, such as Fanconi anaemia or Bloom syndrome, are clinically distinct syndromes characterized by unique pattern of chromosomal damage. These syndromes are associated with a predisposition to cancer, including haematological malignancies. Blood cells in patients with these syndromes might be affected by unique catalogue of driver mutations associated with a cancer predisposition. In this study, we study the driver landscape of blood cells in patients with chromosomal instability syndromes using Targeted (exome) Nanoseq (aiming for ~100X).","abstract":"Blood cells in patients with these syndromes might be affected by unique catalogue of driver mutations associated with a cancer predisposition. In this study, we study the driver landscape of blood cells in patients with chromosomal instability syndromes using Targeted (exome) Nanoseq (aiming for ~100X).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007326","title":"Identifying_The_Effects_Of_Human_Gene_Knockouts_In_Immune_Cells_Using_Single_Cell_Transcriptomics","description":"Around 100 individuals from a community-based cohort that have rare protein truncating variants predicted to affect 22 immune-related genes were recalled. Single-cell RNA profiling was performed on blood samples from these individuals. The goal was to characterise the effect of the gene mutations on the blood transcriptome and immune processes.","abstract":"Loss-of-function variants (LoFs) can serve as naturally-occurring gene ‘knockouts’, allowing in vivo human studies on the function and expression of affected genes (and suggest potential drug targets). We aim to study LoFs in genes associated with immune traits and their effects on the immune cell transcriptome. We have recalled around 100 individuals from Genes and Health with LoFs in immune genes in order to perform single-cell RNA profiling (and other molecular assays) on blood samples collected from these individuals. We hypothesise that there will be decreased expression of gene transcripts that harbour these LoFs. Subsequently, these effects may result in changes in gene expression in whole pathways and cell type proportions. These differences could lead to immune traits that can be further analysed in the participants’ health records.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007327","title":"Pediatric Patient-Derived-Xenograft development in MAPPYACTS – international pediatric cancer precision medicine trial in relapsed and refractory tumors","description":"Pediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962).\n\nTo date, 131 PDX models were established following heterotopical and/or orthotopical implantation in immunocompromised mice: 76 sarcomas, 25 other solid tumors, 12 central nervous system tumors, 15 acute leukemias, and 3 lymphomas. PDX establishment rate was 43%. Histology, whole exome and RNA sequencing revealed a high concordance with the primary patient’s tumor profile, human leukocyte-antigen characteristics and specific metabolic pathway signatures. A detailed patient molecular characterization, including specific mutations prioritized in the clinical molecular tumor boards are provided. Ninety models were shared with the IMI2 ITCC Paediatric Preclinical Proof-of-concept Platform (IMI2 ITCC-P4) for further exploitation.\n\nThis new PDX biobank of unique recurrent childhood cancers provides an essential support for basic and translational research and new treatments development in advanced pediatric malignancies.","abstract":"Pediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962).\n\nTo date, 131 PDX models were established following heterotopical and/or orthotopical implantation in immunocompromised mice: 76 sarcomas, 25 other solid tumors, 12 central nervous system tumors, 15 acute leukemias, and 3 lymphomas. PDX establishment rate was 43%. Histology, whole exome and RNA sequencing revealed a high concordance with the primary patient’s tumor profile, human leukocyte-antigen characteristics and specific metabolic pathway signatures. A detailed patient molecular characterization, including specific mutations prioritized in the clinical molecular tumor boards are provided. Ninety models were shared with the IMI2 ITCC Paediatric Preclinical Proof-of-concept Platform (IMI2 ITCC-P4) for further exploitation.\n\nThis new PDX biobank of unique recurrent childhood cancers provides an essential support for basic and translational research and new treatments development in advanced pediatric malignancies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-08T13:10:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007328","title":"Single-cell characterization of PBMCs from Crohn's disease patients responders and non-responders to vedolizumab","description":null,"abstract":"The goal of this project was to identify differences at a single-cell level between Crohn's disease patients that were classified as responders and non-responders to vedolizumab. PBMC samples were taken at time of response assessment.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007329","title":"Molecular_and_immune_landscape_and_etiology_of_acral_lentiginous_melanoma_WES","description":"Acral lentiginous melanoma (ALM) is a rare subtype of melanoma associated with poor survival. Unlike other cutaneous melanoma subtypes, ALM has not been linked to sun exposure, and much of its risk factors and exposures remain unknown. The clinical, pathological, and genomic characteristics of ALM are also distinct from sun-exposed melanomas. To better understand the etiology, prevention, and treatment of ALM, studies that comprehensively characterize the genomic, transcriptomic, and immune landscape of ALM are needed. So far, such studies have been limited by small sample sizes (n = 1–122); some had a limited number of genes tested, and many did not have both DNA and RNA sequencing data. In addition, Mediterranean populations are also under-represented in melanoma research in general. \n \nNCI is conducting a study of ALM which assembles clinical and epidemiologic data, pathology images, and biospecimens from participating centers in the Mediterranean region. DNA and RNA were extracted for whole-exome sequencing (WES) and RNA sequencing.","abstract":"Acral lentiginous melanoma (ALM) is a rare subtype of melanoma associated with poor survival. Unlike other cutaneous melanoma subtypes, ALM has not been linked to sun exposure, and much of its risk factors and exposures remain unknown. The clinical, pathological, and genomic characteristics of ALM are also distinct from sun-exposed melanomas. To better understand the etiology, prevention, and treatment of ALM, studies that comprehensively characterize the genomic, transcriptomic, and immune landscape of ALM are needed. So far, such studies have been limited by small sample sizes (n = 1–122); some had a limited number of genes tested, and many did not have both DNA and RNA sequencing data. In addition, Mediterranean populations are also under-represented in melanoma research in general. \n \nNCI is conducting a study of ALM which assembles clinical and epidemiologic data, pathology images, and biospecimens from participating centers in the Mediterranean region. DNA and RNA were extracted for whole-exome sequencing (WES) and RNA sequencing.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007330","title":"DECONVOLUTION OF HEMATOPOIETIC STEM/PROGENITOR CELL SIGNALING IN HUMAN AML","description":"A comprehensive taxonomy of the predicted interactions between LEPR + stromal niches, HSPCs and adaptive/innate immune cells in the human NBM and AML","abstract":"A comprehensive taxonomy of the predicted interactions between LEPR + stromal niches, HSPCs and adaptive/innate immune cells in the human NBM and AML","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-09T15:15:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007331","title":"H3Africa - Stroke Investigative Research and Education Networks","description":"Although stroke is a discrete phenotype, it is the clinical culmination of several complex and interacting biological processes, precipitated by various genetic and environmental factors, thereby making ready analyses of its underlying mechanisms a challenge. However, the formulation of successful tailor-made prevention strategies for limiting the immense personal and societal burden of stroke in Sub-Saharan Africa (SSA) is contingent on a better understanding of the predisposing risk factors for stroke in the region, which may not necessarily match the nature of stroke risk factors described among other people on other continents. Indeed, the underlying risk factors for stroke in SSA have hitherto not been comprehensively characterized, and currently there is a paucity of expertise, experience, and infrastructure in genomics and environmental research in SSA, to initiate and sustain such investigation. We seek to establish the Stroke Investigative Research and Education Network (SIREN) as a multidisciplinary collaborative research network of investigators in SSA and the United States collectively focused on exploring ways to promote a better understanding of the genetic and environmental risk factors for stroke among people of African ancestry. SIREN will evaluate unique contributors to stroke in SSA and compare these findings with those in a cohort of African American stroke survivors, all while simultaneously building sustainable capacities in phenomics, biobanking, genomics, biostatistics and bioinformatics for future high-level investigation of stroke and other vascular disease entities in SSA.","abstract":"Although stroke is a discrete phenotype, it is the clinical culmination of several complex and interacting biological processes, precipitated by various genetic and environmental factors, thereby making ready analyses of its underlying mechanisms a challenge. However, the formulation of successful tailor-made prevention strategies for limiting the immense personal and societal burden of stroke in Sub-Saharan Africa (SSA) is contingent on a better understanding of the predisposing risk factors for stroke in the region, which may not necessarily match the nature of stroke risk factors described among other people on other continents. Indeed, the underlying risk factors for stroke in SSA have hitherto not been comprehensively characterized, and currently there is a paucity of expertise, experience, and infrastructure in genomics and environmental research in SSA, to initiate and sustain such investigation. We seek to establish the Stroke Investigative Research and Education Network (SIREN) as a multidisciplinary collaborative research network of investigators in SSA and the United States collectively focused on exploring ways to promote a better understanding of the genetic and environmental risk factors for stroke among people of African ancestry. SIREN will evaluate unique contributors to stroke in SSA and compare these findings with those in a cohort of African American stroke survivors, all while simultaneously building sustainable capacities in phenomics, biobanking, genomics, biostatistics and bioinformatics for future high-level investigation of stroke and other vascular disease entities in SSA.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-09T16:29:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007332","title":"Bone marrow single cell genomics from blood cancer samples","description":"The overall goal of this study was to characterize bone marrow cells based on their transcriptome, surface protein expression and BCR- and TCR VDJ-profile for accurate identification of clinically relevant cell states.  This project has received funding from the European Union Horizon 2020 research and innovation programme under grant agreement No 824110 (EASI-Genomics)","abstract":"The overall goal of this study was to characterize bone marrow cells based on their transcriptome, surface protein expression and BCR- and TCR VDJ-profile for accurate identification of clinically relevant cell states.  This project has received funding from the European Union Horizon 2020 research and innovation programme under grant agreement No 824110 (EASI-Genomics)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-09T22:10:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007333","title":"Detection of somatic mutations of angioimmunoblastic T-cell lymphoma","description":null,"abstract":"AITL tumor samples were used for whole exome sequencing. Somatic mutations were identified.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-11T07:07:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007334","title":"Facial Skin Biophysical Multi-Parameter and Microbiome-Based Korean Skin Cutoype (KSC) Determination","description":"In this study, we conducted an integrated analysis of skin measurements, clinical BSTI surveys, and the skin microbiome of 950 Korean subjects to examine the ideal skin microbiome-biophysical association. By utilizing four skin biophysical parameters, we identified four distinct Korean Skin Cutotypes (KSCs) and categorized the subjects into three aging groups based on their age distribution. We established strong connections between 15 core genera and the four KSC types within the three aging groups, revealing three prominent clusters of the facial skin microbiome. Together with skin microbiome variations, skin tone/elasticity distinguishes aging groups while oiliness/hydration distinguishes individual differences within aging groups. Our study provides prospective reality data for customized skin care based on the microbiome environment of each skin type.","abstract":"In this study, we conducted an integrated analysis of skin measurements, clinical BSTI surveys, and the skin microbiome of 950 Korean subjects to examine the ideal skin microbiome-biophysical association. By utilizing four skin biophysical parameters, we identified four distinct Korean Skin Cutotypes (KSCs) and categorized the subjects into three aging groups based on their age distribution. We established strong connections between 15 core genera and the four KSC types within the three aging groups, revealing three prominent clusters of the facial skin microbiome. Together with skin microbiome variations, skin tone/elasticity distinguishes aging groups while oiliness/hydration distinguishes individual differences within aging groups. Our study provides prospective reality data for customized skin care based on the microbiome environment of each skin type.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-12T06:13:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007335","title":"FGFR-driven urothelial cancer","description":null,"abstract":"We performed a global mutational landscape analysis using tumor samples from the 47 urothelial cancer patients included in MATCH-R or MOSCATO studies, with advanced metastatic disease and WES available (RNAseq is included for 38 patient samples). The most frequently altered genes were TP53 (51%), FGFR3 (34%), and KMT2D (34%).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-12T13:17:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007336","title":"Breast cancer sequencing data","description":null,"abstract":"Human breast cancer sequencing datasets, which include spatial and single-cell antigen receptor repertoire profiling and spatial and single-cell transcriptomics (10x genomics). This study includes multiple samples from two individual HER2+ patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-12T14:15:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007337","title":"Tonsil Sequencing dataset","description":null,"abstract":"Human tonsil tissue sequencing datasets, which include spatial antigen receptor repertoire profiling and spatial transcriptomics (Visium). This study includes two samples.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-12T14:16:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007338","title":"Molecular_and_immune_landscape_and_etiology_of_acral_lentiginous_melanoma_RNAseq","description":"Acral lentiginous melanoma (ALM) is a rare subtype of melanoma associated with poor survival. Unlike other cutaneous melanoma subtypes, ALM has not been linked to sun exposure, and much of its risk factors and exposures remain unknown. The clinical, pathological, and genomic characteristics of ALM are also distinct from sun-exposed melanomas. To better understand the etiology, prevention, and treatment of ALM, studies that comprehensively characterize the genomic, transcriptomic, and immune landscape of ALM are needed. So far, such studies have been limited by small sample sizes (n = 1–122); some had a limited number of genes tested, and many did not have both DNA and RNA sequencing data. In addition, Mediterranean populations are also under-represented in melanoma research in general. \n \nNCI is conducting a study of ALM which assembles clinical and epidemiologic data, pathology images, and biospecimens from participating centers in the Mediterranean region. DNA and RNA were extracted for whole-exome sequencing (WES) and RNA sequencing.","abstract":"Acral lentiginous melanoma (ALM) is a rare subtype of melanoma associated with poor survival. Unlike other cutaneous melanoma subtypes, ALM has not been linked to sun exposure, and much of its risk factors and exposures remain unknown. The clinical, pathological, and genomic characteristics of ALM are also distinct from sun-exposed melanomas. To better understand the etiology, prevention, and treatment of ALM, studies that comprehensively characterize the genomic, transcriptomic, and immune landscape of ALM are needed. So far, such studies have been limited by small sample sizes (n = 1–122); some had a limited number of genes tested, and many did not have both DNA and RNA sequencing data. In addition, Mediterranean populations are also under-represented in melanoma research in general. \n \nNCI is conducting a study of ALM which assembles clinical and epidemiologic data, pathology images, and biospecimens from participating centers in the Mediterranean region. DNA and RNA were extracted for whole-exome sequencing (WES) and RNA sequencing.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007339","title":"Long-read sequencing identifies a common transposition haplotype predisposing for CLCNKB deletions","description":"Long-read whole genome sequencing, long-read long-range PCR sequencing, targetted long fragment long-read sequencing data of the CLCNKA/CLCNKB locus in 27 Bartter syndrome patients.\nMultiple different deletion alleles are identified and a new common transposition haplotype predisposing for CLCNKB deletions is described.","abstract":"Long-read whole genome sequencing, long-read long-range PCR sequencing, targetted long fragment long-read sequencing data of the CLCNKA/CLCNKB locus in 27 Bartter syndrome patients.\nMultiple different deletion alleles are identified and a new common transposition haplotype predisposing for CLCNKB deletions is described.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-12T15:37:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007340","title":"Linked-read based analysis of high-grade gliomas genomes","description":null,"abstract":"Research over the last decade has shown that pediatric high-grade gliomas (pHGGs) are separate entities from adult gliomas with distinct molecular profiles. While pHGGs are mainly characterized by the presence or absence of mutually exclusive mutations in histone-encoding genes (H3F3A or HIST1H3B) or IDH1/2, many other genes have been found to be recurrently co-mutated, deleted, amplified, and affected by structural variants all of which may serve as potential therapeutic targets. We used linked-read sequencing to determine whether we could characterize the spectrum of different types of mutation that affect recurrently mutated genes in HGGs. We show that linked-reads can be used to identify point mutations, structural variants, copy number changes as well as extrachromosomal DNA using minimal gDNA input (&lt;10ng) making them an attractive option for clinical diagnosis.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007341","title":"Total proteome and phosphoproteome profiling of Diffuse Midline Glioma","description":null,"abstract":"Deep proteomics profiling including total proteome and phosphoproteome of diffuse midline glioma tissues were carried out to identify differentially expressed proteins and differentially phosphorylated proteins in DMG tissues compared to normal brains.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-12T21:38:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007342","title":"Methylproteome profiling of Diffuse Midline Glioma","description":null,"abstract":"Global protein methylation of DMG tissues was profiled using LC-MS3 to identify differentially methylated proteins in DMG tissues compared to normal brains were identified.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-12T21:38:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007343","title":"ATAC-Seq of healthy and IBD blood samples","description":"PBMCs from blood samples of 9 age- and gender-matched healthy subjects and 25 IBD patients were isolated through a Ficoll density gradient and used to isolate live CD4 T cells through a magnetic cell isolation kit (Miltenyi Biotec). Twelve thousand live CD4 T cells were then used to prepare ATAC-Seq libraries. Briefly, crude nuclei of live CD4+ T cells were treated with Tagment DNA buffer and Tagment DNA Enzyme (Nextera DNA Library Prep Kit, Illumina), and then the DNA was purified by MinElute PCR Purification Kit (Qiagen). Transposed DNA fragments were amplified using specific adapters followed by purification with MinElute PCR Purification Kit (Qiagen). Fragments from 240-360pb were selected in the PippinHT system (Sage Science). The quality of the library and its DNA concentration were assessed by Bioanalyzer instruments (Agilent Technologies) and ultimately submitted for sequencing using Illumina HiSeq 2500 sequencer, V4 chemistry.","abstract":"PBMCs from blood samples of 9 age- and gender-matched healthy subjects and 25 IBD patients were isolated through a Ficoll density gradient and used to isolate live CD4 T cells through a magnetic cell isolation kit (Miltenyi Biotec). Twelve thousand live CD4 T cells were then used to prepare ATAC-Seq libraries. Briefly, crude nuclei of live CD4+ T cells were treated with Tagment DNA buffer and Tagment DNA Enzyme (Nextera DNA Library Prep Kit, Illumina), and then the DNA was purified by MinElute PCR Purification Kit (Qiagen). Transposed DNA fragments were amplified using specific adapters followed by purification with MinElute PCR Purification Kit (Qiagen). Fragments from 240-360pb were selected in the PippinHT system (Sage Science). The quality of the library and its DNA concentration were assessed by Bioanalyzer instruments (Agilent Technologies) and ultimately submitted for sequencing using Illumina HiSeq 2500 sequencer, V4 chemistry.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-12T23:23:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007344","title":"ATAC-Seq of inflamed and non-inflamed biopsies","description":"Inflamed and non-inflamed biopsies were digested for 45 minutes at 37ºC with collagenase from Clostridium histolyticum (Sigma). Suspension cells were then stained with an antibody cocktail to sort live CD8-CD4+ T cells. After isolating crude nuclei of two thousand live CD4+ T cells, they were treated with Tagment DNA buffer and Tagment DNA Enzyme (Nextera DNA Library Prep Kit, Illumina), and then the DNA was purified by MinElute PCR Purification Kit (Qiagen). Transposed DNA fragments were amplified using specific adapters followed by purification with MinElute PCR Purification Kit (Qiagen). Fragments from 240-360pb were selected in the PippinHT system (Sage Science). The quality of the library and its DNA concentration were assessed by Bioanalyzer instruments (Agilent Technologies) and ultimately submitted for sequencing using Illumina HiSeq 2500 sequencer, V4 chemistry.","abstract":"Inflamed and non-inflamed biopsies were digested for 45 minutes at 37ºC with collagenase from Clostridium histolyticum (Sigma). Suspension cells were then stained with an antibody cocktail to sort live CD8-CD4+ T cells. After isolating crude nuclei of two thousand live CD4+ T cells, they were treated with Tagment DNA buffer and Tagment DNA Enzyme (Nextera DNA Library Prep Kit, Illumina), and then the DNA was purified by MinElute PCR Purification Kit (Qiagen). Transposed DNA fragments were amplified using specific adapters followed by purification with MinElute PCR Purification Kit (Qiagen). Fragments from 240-360pb were selected in the PippinHT system (Sage Science). The quality of the library and its DNA concentration were assessed by Bioanalyzer instruments (Agilent Technologies) and ultimately submitted for sequencing using Illumina HiSeq 2500 sequencer, V4 chemistry.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-12T23:23:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007345","title":"ATAC-Seq of CD4 T cell subsets","description":"Blood samples were taken from 4 age-matched healthy volunteers (two males and two females), and naïve CD4 T cells were isolated using the naïve CD4+ T Cell Isolation Kit II, human (Miltenyi Biotec). Two hundred thousand cells were plated in a 96-well\n\nplate, activated with Dynabeads Human T-activator CD3/CD28 (bead-to-cell ratio of 1:1, as recommended by the manufacturer) (ThermoFisher Scientific) and polarized towards CD4 T cell subtypes (Teff, Th1, Th2, rTh17, pTh17, and Treg cells) with specific cocktails of recombinant cytokines and neutralizing antibodies (see details in the material and methods) for each subset. At day 4 post-stimulation, forty thousand cells were used to perform ATAC-Seq on CD4 T cell subtypes. Again, crude nuclei of live CD4+ T cell subsets were treated with Tagment DNA buffer and Tagment DNA Enzyme (Nextera DNA Library Prep Kit, Illumina), and then the DNA was purified by MinElute PCR Purification Kit (Qiagen). Transposed DNA fragments were amplified using specific adapters followed by purification with MinElute PCR Purification Kit (Qiagen). Fragments from 240-360pb were selected in the PippinHT system (Sage Science). The quality of the library and its DNA concentration were assessed by Bioanalyzer instruments (Agilent Technologies) and ultimately submitted for sequencing using Illumina HiSeq 2500 sequencer, V4 chemistry.","abstract":"Blood samples were taken from 4 age-matched healthy volunteers (two males and two females), and naïve CD4 T cells were isolated using the naïve CD4+ T Cell Isolation Kit II, human (Miltenyi Biotec). Two hundred thousand cells were plated in a 96-well\n\nplate, activated with Dynabeads Human T-activator CD3/CD28 (bead-to-cell ratio of 1:1, as recommended by the manufacturer) (ThermoFisher Scientific) and polarized towards CD4 T cell subtypes (Teff, Th1, Th2, rTh17, pTh17, and Treg cells) with specific cocktails of recombinant cytokines and neutralizing antibodies (see details in the material and methods) for each subset. At day 4 post-stimulation, forty thousand cells were used to perform ATAC-Seq on CD4 T cell subtypes. Again, crude nuclei of live CD4+ T cell subsets were treated with Tagment DNA buffer and Tagment DNA Enzyme (Nextera DNA Library Prep Kit, Illumina), and then the DNA was purified by MinElute PCR Purification Kit (Qiagen). Transposed DNA fragments were amplified using specific adapters followed by purification with MinElute PCR Purification Kit (Qiagen). Fragments from 240-360pb were selected in the PippinHT system (Sage Science). The quality of the library and its DNA concentration were assessed by Bioanalyzer instruments (Agilent Technologies) and ultimately submitted for sequencing using Illumina HiSeq 2500 sequencer, V4 chemistry.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-12T23:23:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007346","title":"Modulation of the peripheral blood immune cell transcriptome by vitamin D3 supplementation in people with a first demyelinating event: a randomized placebo-controlled trial","description":"Vitamin D deficiency is a risk factor for developing multiple sclerosis (MS). Both in vitro and animal studies suggest an immunomodulatory effect of vitamin D. The PrevANZ trial, a phase IIb randomized placebo-controlled trial of oral vitamin D3 supplementation in people with a first demyelinating event (FDE), was conducted to determine if supplementation can prevent recurrent disease activity in this cohort at high risk of developing definite MS. As a sub-study of this trial, we used whole blood transcriptomic analyses to investigate the effect of vitamin D3 supplementation on peripheral immune cells in people with an FDE, and to gain insight into potential mechanisms by which vitamin D3 may regulate MS risk and disease activity. The PrevANZ trial randomized participants to 1000 IU, 5000 IU or 10,000 IU daily of oral vitamin D3 or placebo. Peripheral blood was collected at baseline and 12 weeks in PAXgene Blood RNA tubes. Transcriptomic datasets were generated by RNA sequencing.","abstract":"Vitamin D deficiency is a risk factor for developing multiple sclerosis (MS). Both in vitro and animal studies suggest an immunomodulatory effect of vitamin D. The PrevANZ trial, a phase IIb randomized placebo-controlled trial of oral vitamin D3 supplementation in people with a first demyelinating event (FDE), was conducted to determine if supplementation can prevent recurrent disease activity in this cohort at high risk of developing definite MS. As a sub-study of this trial, we used whole blood transcriptomic analyses to investigate the effect of vitamin D3 supplementation on peripheral immune cells in people with an FDE, and to gain insight into potential mechanisms by which vitamin D3 may regulate MS risk and disease activity. The PrevANZ trial randomized participants to 1000 IU, 5000 IU or 10,000 IU daily of oral vitamin D3 or placebo. Peripheral blood was collected at baseline and 12 weeks in PAXgene Blood RNA tubes. Transcriptomic datasets were generated by RNA sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-14T01:23:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007347","title":"'IL-17A-Producing ILC3s and Duodenal Adenoma in FAP'","description":"Familial Adenomatous Polyposis (FAP) is a hereditary tumor syndrome that significantly enhances the risk of duodenal adenomas, with variations observed even among carriers of the same genetic variant. In this study, intestinal ILCs were isolated from 82 FAP and 26 non-FAP patients and analyzed through flow cytometry, qRT-PCR, and bulkRNA-sequencing. The data revealed a heightened frequency of ILC3s in FAP patients, and increased IL-17A production of duodenal NKp44(-)ILC3s was associated with FAP. Significant elevations in IL1B, IL23A, and DLL4 mRNA expression levels were found in FAP duodenal adenoma tissue, along with enhanced expression of DUOX2 and DUOXA2. The results suggest the involvement of IL-17A-producing NKp44(-)ILC3s in duodenal adenoma formation in FAP.","abstract":"Familial Adenomatous Polyposis (FAP) is a hereditary tumor syndrome that significantly enhances the risk of duodenal adenomas, with variations observed even among carriers of the same genetic variant. In this study, intestinal ILCs were isolated from 82 FAP and 26 non-FAP patients and analyzed through flow cytometry, qRT-PCR, and bulkRNA-sequencing. The data revealed a heightened frequency of ILC3s in FAP patients, and increased IL-17A production of duodenal NKp44(-)ILC3s was associated with FAP. Significant elevations in IL1B, IL23A, and DLL4 mRNA expression levels were found in FAP duodenal adenoma tissue, along with enhanced expression of DUOX2 and DUOXA2. The results suggest the involvement of IL-17A-producing NKp44(-)ILC3s in duodenal adenoma formation in FAP.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-14T09:32:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007348","title":"Molecular features predict hepatoblastoma survival","description":"Hepatoblastoma is the most frequent pediatric liver cancer. The current treatments lead to 80% of survival rate at 5 years. In this study, we evaluated the clinical relevance of molecular features to identify patients at risk of chemoresistance, relapse and death of disease.\nAll the clinical data of 86 children with hepatoblastoma were retrospectively collected. Pathological slides were reviewed, and tumor DNA sequencing (by whole exome, whole genome or target) and transcriptomic profiling with RNAseq or 300-genes panel were performed. Associations between the clinical, pathological, mutational and transcriptomic data were investigated.\nHigh-risk patients represented 44% of our series and the median age at diagnosis was 21.9 months (range: 0-208). Alterations of the WNT/ß-catenin pathway and of the 11p15.5 imprinted locus were identified in 98% and 74% of the tumors, respectively. Other cancer driver genes mutations were only found in less than 11% of tumors. After neoadjuvant chemotherapy, disease-specific survival and poor response to neoadjuvant chemotherapy were associated with ‘Liver Progenitor’ (p=0.00049, p&lt;0.0001) and ‘Immune Cold’ (p=0.0011, p&lt;0.0001) transcriptomic tumor subtypes, SBS35 cisplatin mutational signature (p=0.018, p=0.001), mutations in rare cancer driver genes (p=0.0039, p=0.0017) and embryonal predominant histological type (p=0.0013, p=0.0077), respectively. Integration of the clinical and molecular features revealed a cluster of molecular markers associated with resistance to chemotherapy and survival, enlightening transcriptomic ‘Immune Cold’ and Liver Progenitor’ as a predictor of survival independent of the clinical features.\nResponse to neoadjuvant chemotherapy and survival in children treated for hepatoblastoma are associated with genomic and pathological features independently of the clinical features.","abstract":"Hepatoblastoma is the most frequent pediatric liver cancer. The current treatments lead to 80% of survival rate at 5 years. In this study, we evaluated the clinical relevance of molecular features to identify patients at risk of chemoresistance, relapse and death of disease.\nAll the clinical data of 86 children with hepatoblastoma were retrospectively collected. Pathological slides were reviewed, and tumor DNA sequencing (by whole exome, whole genome or target) and transcriptomic profiling with RNAseq or 300-genes panel were performed. Associations between the clinical, pathological, mutational and transcriptomic data were investigated.\nHigh-risk patients represented 44% of our series and the median age at diagnosis was 21.9 months (range: 0-208). Alterations of the WNT/ß-catenin pathway and of the 11p15.5 imprinted locus were identified in 98% and 74% of the tumors, respectively. Other cancer driver genes mutations were only found in less than 11% of tumors. After neoadjuvant chemotherapy, disease-specific survival and poor response to neoadjuvant chemotherapy were associated with ‘Liver Progenitor’ (p=0.00049, p&lt;0.0001) and ‘Immune Cold’ (p=0.0011, p&lt;0.0001) transcriptomic tumor subtypes, SBS35 cisplatin mutational signature (p=0.018, p=0.001), mutations in rare cancer driver genes (p=0.0039, p=0.0017) and embryonal predominant histological type (p=0.0013, p=0.0077), respectively. Integration of the clinical and molecular features revealed a cluster of molecular markers associated with resistance to chemotherapy and survival, enlightening transcriptomic ‘Immune Cold’ and Liver Progenitor’ as a predictor of survival independent of the clinical features.\nResponse to neoadjuvant chemotherapy and survival in children treated for hepatoblastoma are associated with genomic and pathological features independently of the clinical features.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007349","title":"Organoid_Derivation_Project___GRCh38___TGS","description":"Generation of normal and cancer organoids for sequencing as part of the WTSI-CRUK international collaboration with NCI (in HCMI) to generate the next generation of cancer cell lines.","abstract":"Generation of normal and cancer organoids for sequencing as part of the WTSI-CRUK international collaboration with NCI (in HCMI) to generate the next generation of cancer cell lines.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-16T15:40:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007350","title":"A circulating biomarker for severity of facioscapulohumeral muscular dystrophy","description":"Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, incurable skeletal myopathy. Clinical trials for FSHD are hindered by heterogeneous biomarkers poorly associated with clinical severity, requiring invasive muscle biopsy. Macroscopically FSHD presents with slow fatty replacement of muscle, rapidly accelerated by inflammation. Mis-expression of the transcription factor DUX4 is currently accepted to underlie FSHD pathogenesis and mechanisms including PAX7 target gene repression have been proposed. \nHere we perform RNA-sequencing on MRI guided inflamed (n=24) and isogenic non-inflamed (n=24) muscle biopsies from the same clinically characterised FSHD patients, alongside isogenic peripheral blood mononucleated cells from a subset of patients (n=13), and unaffected controls. We employ multivariate models to evaluate the clinical associations of 5 published FSHD transcriptomic biomarkers.\nWe demonstrate that PAX7 target gene repression can discriminate control, inflamed and non-inflamed FSHD muscle independently of age and sex (p&lt;0.013), while the discriminatory power of DUX4 target genes is limited to distinguishing FSHD muscle from control. Importantly, the level of PAX7 target gene repression in non-inflamed muscle associates with clinical assessments of FSHD severity (p=0.04). DUX4 target gene biomarkers in FSHD muscle show associations with lower limb fat fraction and D4Z4 array length, but not clinical assessment. Lastly, PAX7 target gene repression in FSHD muscle correlates with the level in isogenic peripheral blood mononucleated cells (p=0.002). A refined PAX7 target gene biomarker comprising 143/601 PAX7 target genes computed in peripheral blood (the FSHD muscle-blood biomarker) associates with clinical severity in FSHD patients (p&lt;0.036). Our new circulating biomarker validates as a classifier of clinical severity in an independent data set of 54 FSHD patient blood samples, with improved power in older patients (p=0.03). \nIn summary, we present the minimally invasive FSHD muscle-blood biomarker of FSHD clinical severity valid in patient muscle and blood, with potential utility in routine disease monitoring and clinical trials.","abstract":"Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, incurable skeletal myopathy. Clinical trials for FSHD are hindered by heterogeneous biomarkers poorly associated with clinical severity, requiring invasive muscle biopsy. Macroscopically FSHD presents with slow fatty replacement of muscle, rapidly accelerated by inflammation. Mis-expression of the transcription factor DUX4 is currently accepted to underlie FSHD pathogenesis and mechanisms including PAX7 target gene repression have been proposed. \nHere we perform RNA-sequencing on MRI guided inflamed (n=24) and isogenic non-inflamed (n=24) muscle biopsies from the same clinically characterised FSHD patients, alongside isogenic peripheral blood mononucleated cells from a subset of patients (n=13), and unaffected controls. We employ multivariate models to evaluate the clinical associations of 5 published FSHD transcriptomic biomarkers.\nWe demonstrate that PAX7 target gene repression can discriminate control, inflamed and non-inflamed FSHD muscle independently of age and sex (p&lt;0.013), while the discriminatory power of DUX4 target genes is limited to distinguishing FSHD muscle from control. Importantly, the level of PAX7 target gene repression in non-inflamed muscle associates with clinical assessments of FSHD severity (p=0.04). DUX4 target gene biomarkers in FSHD muscle show associations with lower limb fat fraction and D4Z4 array length, but not clinical assessment. Lastly, PAX7 target gene repression in FSHD muscle correlates with the level in isogenic peripheral blood mononucleated cells (p=0.002). A refined PAX7 target gene biomarker comprising 143/601 PAX7 target genes computed in peripheral blood (the FSHD muscle-blood biomarker) associates with clinical severity in FSHD patients (p&lt;0.036). Our new circulating biomarker validates as a classifier of clinical severity in an independent data set of 54 FSHD patient blood samples, with improved power in older patients (p=0.03). \nIn summary, we present the minimally invasive FSHD muscle-blood biomarker of FSHD clinical severity valid in patient muscle and blood, with potential utility in routine disease monitoring and clinical trials.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-19T09:29:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007351","title":"Assessing mitochondrial bioenergetics in coronary artery disease: A translational left ventricular tissue study in humans (The AMBITION study).","description":"Severe or recurrent myocardial ischemia can lead to long-term left ventricular (LV) dysfunction and heart failure in patients with coronary artery disease (CAD). In this study, we assessed for chronic metabolomic and transcriptomic adaptations within LV myocardium of patients with evidence of preoperative inducible ischemia undergoing coronary artery bypass grafting (CABG). During surgery, paired transmural LV biopsies were acquired on the beating heart from a region of inducible ischemia (determined by stress perfusion cardiovascular magnetic resonance), and a remote LV segment. From 33 patients, 63 LV biopsies were acquired on the beating heart during CABG, comparing to analysis of LV samples from 11 donor hearts. The global myocardial ATP/ADP ratio was reduced in CAD patients as compared to donor LV tissue with increased expression of oxidative phosphorylation (OXPHOS) genes encoding the electron transport chain complexes across multiple cell types. Paired analyses of biopsies obtained during CABG from LV segments with or without inducible ischemia revealed no significant difference in the ATP/ADP ratio, broader metabolic profile or expression of ventricular cardiomyocyte genes implicated in OXPHOS. Finally, differential metabolite analysis suggested dysregulation of several intermediates in patients with impaired LVEF; this notably included the tricyclic acid cycle metabolite, succinate. Overall, our results suggest that viable human myocardium in patients with stable CAD has global alterations in bioenergetic and transcriptional profile without large regional differences between areas with or without inducible ischemia.","abstract":"Severe or recurrent myocardial ischemia can lead to long-term left ventricular (LV) dysfunction and heart failure in patients with coronary artery disease (CAD). In this study, we assessed for chronic metabolomic and transcriptomic adaptations within LV myocardium of patients with evidence of preoperative inducible ischemia undergoing coronary artery bypass grafting (CABG). During surgery, paired transmural LV biopsies were acquired on the beating heart from a region of inducible ischemia (determined by stress perfusion cardiovascular magnetic resonance), and a remote LV segment. From 33 patients, 63 LV biopsies were acquired on the beating heart during CABG, comparing to analysis of LV samples from 11 donor hearts. The global myocardial ATP/ADP ratio was reduced in CAD patients as compared to donor LV tissue with increased expression of oxidative phosphorylation (OXPHOS) genes encoding the electron transport chain complexes across multiple cell types. Paired analyses of biopsies obtained during CABG from LV segments with or without inducible ischemia revealed no significant difference in the ATP/ADP ratio, broader metabolic profile or expression of ventricular cardiomyocyte genes implicated in OXPHOS. Finally, differential metabolite analysis suggested dysregulation of several intermediates in patients with impaired LVEF; this notably included the tricyclic acid cycle metabolite, succinate. Overall, our results suggest that viable human myocardium in patients with stable CAD has global alterations in bioenergetic and transcriptional profile without large regional differences between areas with or without inducible ischemia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-19T11:34:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007352","title":"SVUH Under-50 CRC","description":null,"abstract":"Determine genomic anomalies in under-50's patients developing colorectal cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007353","title":"Macrophage_Ontogeny___EMseq","description":"Macrophages play critical roles in human disease through defence, regulation and repair . Once thought to arise from monocytes, recent data indicate that they originate and renew in diverse ways . Microglia arise from primitive yolk sac progenitors and remain independent of definitive haematopoiesis . Kupffer cells and alveolar macrophages are formed by fetal liver monocytes but become independent of haematopoiesis, unless perturbed . In many tissues, notably skin and gut, both long-lived primitive origin and recently recruited haematogenous macrophages can be found; their origin and mode of homeostasis linked to profound functional differences. We and others have shown that parallels exist in humans, using transplantation and genetic deficiency . However, these are perturbed states, populations such as microglia are difficult to access, and the potential founding role of the human yolk sac has not been interrogated \nIn this study we will be performing WGS of hundreds of single-cell derived foetal colonies/ organoids, derived from a tissues originating from all three germ layers (ectoderm, mesoderm and endoderm), as well as non-embryonic tissues such as the yolk sac. This will be used to define a foetal developmental phylogeny where mutations characterising different developmental lineages are defined.  These mutations will be used to design a custom bait set that will be applied in a high depth targeted sequencing approach of a braod array of foetal tissues/ cell types to help define their developmental origins and dynamics.","abstract":"Acquired somatic mutation is a pervasive influence on the genomes of multicellular organisms, inevitably playing a major role in human disease. 1) Somatic mutation offers a fate-mapping tool to probe lineage relationships, previously only accessible in animals. 2) Within haematopoiesis, mutations generate age-related clonal populations, causing subtle yet prevalent acceleration of morbidity. 3) Mutation leads to neoplasia, at times manifest as idiopathic inflammatory disease. My proposal concerns these three aspects of somatic mutation, in relation to the biology of human macrophages. I examine their origin, which may prove critical in resilience to neurodegenerative disease (Aim 1), their potential to accelerate vascular and inflammatory disease in clonal haematopoiesis (Aim 2), and their induction of inflammation when re-wired by neoplastic transformation (Aim 3). Together these define novel and potentially highly exploitable mechanisms of pathology in humans.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007354","title":"The_Little_Princess_Knowledge_Bank_Dupseq","description":"We propose to build a genetic knowledge bank of Wilms tumour that integrates clinical outcome\ndata with a genetic, epigenetic, and transcriptomic survey of 1,000 Wilms tumours.","abstract":"The purpose of the knowledge bank is to serve as a community resource and to address the following specific\nquestions about Wilms tumour:\n(1) Do genetic, epigenetic, or transcriptional features predict outcome and thus lend themselves to\ntreatment stratification?\n(2) What are the genetic drivers of Wilms tumour, considering the entire histological spectrum of\nWilms tumour including the most common subtypes classified as intermediate risk?","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007355","title":"The genomic landscape of GCs","description":"whole-genome sequencing of 168 paired GCs.","abstract":"whole-genome sequencing of 168 paired GCs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-19T14:49:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007356","title":"Intercellular nanotube-mediated mitochondrial transfer enhances T-cell metabolic fitness and antitumor efficacy","description":"We found that bone marrow-derived mesenchymal stromal cells (MSC) establish nanotubular connections with T cells in a Talin 2 (TLN2)-dependent manner and leveraged these intercellular highways to supply new mitochondria to CD8+ T cells. In this experiment we analyzed the transcriptional profile of T cells co-cultured with MSC containing MSC derived Mitochondria (MitoPositive), T cells co-cultured with MSC not containing MSC derived Mitochondria and control T cells.","abstract":"We found that bone marrow-derived mesenchymal stromal cells (MSC) establish nanotubular connections with T cells in a Talin 2 (TLN2)-dependent manner and leveraged these intercellular highways to supply new mitochondria to CD8+ T cells. In this experiment we analyzed the transcriptional profile of T cells co-cultured with MSC containing MSC derived Mitochondria (MitoPositive), T cells co-cultured with MSC not containing MSC derived Mitochondria and control T cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-19T15:18:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007357","title":"Molecular Plasticity Results in Oncofetal Reprogramming and Therapeutic Vulnerabilities in Juvenile Myelomonocytic Leukemia","description":"Aberrant fetal gene expression in cancer is considered to facilitate tumor-specific cellular plasticity by hijacking features of embryogenesis, inflammation, and immunosuppression. In early childhood cancers, prenatal origins might explain preserved fetal gene signatures. In adult malignancies, the reactivation of fetal-like gene expression profiles is considered as a consequence of onco-fetal reprogramming (OFR). Although this phenomenon is often associated with aggressive disease and poor outcome, underlying molecular mechanisms remain elusive. Furthermore, the role of OFR in childhood malignancies is subject to speculation. \nIn the present study we demonstrate that an aggressive form of childhood cancer, high-risk juvenile myelomonocytic leukemia (JMML), is characterized by OFR in hematopoietic stem cells (HSC) that is directly driven by oncogenic RAS signaling. Single-cell transcriptome and low-input DNA methylome analyses of JMML patient samples revealed widespread epigenomic and transcriptomic aberrations, which provided evidence that the disease-initiating cells reside within the HSC compartment. In depth analysis of JMML HSCs revealed complex disease- and subtype-specific patterns characterized by fetal-like expression signatures combined with a predominantly postnatal epigenetic landscape, suggesting onco-fetal reprogramming. To experimentally test this, we employed a JMML mouse model in which we demonstrated that postnatal activation of RAS signaling is sufficient to induce fetal-like molecular signatures in HSCs. In patients, onco-fetal reprogramming triggers variegated developmental programs, leading to altered priming, immune activation, and chronic inflammation of high-risk HSCs. \nMulti-omics analysis of JMML stem cells identified several epitype-specific surface proteins as novel biomarkers for high-risk JMML. Among those factors was CD52, which has previously been described as a fetal stem cell marker. Immunotherapeutic targeting of CD52 led to reduced leukemic engraftment and increased survival in a patient-derived xenograft mouse model, providing a preclinical rationale for further assessment of a CD52-targeted treatment of high-risk JMML. \nThis study implicates oncogenic RAS signaling in the process of onco-fetal reprogramming and demonstrates how aberrantly expressed genes can be identified and leveraged for risk-stratification and the development of novel treatment strategies, as exemplified by an anti-CD52 treatment.","abstract":"Aberrant fetal gene expression in cancer is considered to facilitate tumor-specific cellular plasticity by hijacking features of embryogenesis, inflammation, and immunosuppression. In early childhood cancers, prenatal origins might explain preserved fetal gene signatures. In adult malignancies, the reactivation of fetal-like gene expression profiles is considered as a consequence of onco-fetal reprogramming (OFR). Although this phenomenon is often associated with aggressive disease and poor outcome, underlying molecular mechanisms remain elusive. Furthermore, the role of OFR in childhood malignancies is subject to speculation. \nIn the present study we demonstrate that an aggressive form of childhood cancer, high-risk juvenile myelomonocytic leukemia (JMML), is characterized by OFR in hematopoietic stem cells (HSC) that is directly driven by oncogenic RAS signaling. Single-cell transcriptome and low-input DNA methylome analyses of JMML patient samples revealed widespread epigenomic and transcriptomic aberrations, which provided evidence that the disease-initiating cells reside within the HSC compartment. In depth analysis of JMML HSCs revealed complex disease- and subtype-specific patterns characterized by fetal-like expression signatures combined with a predominantly postnatal epigenetic landscape, suggesting onco-fetal reprogramming. To experimentally test this, we employed a JMML mouse model in which we demonstrated that postnatal activation of RAS signaling is sufficient to induce fetal-like molecular signatures in HSCs. In patients, onco-fetal reprogramming triggers variegated developmental programs, leading to altered priming, immune activation, and chronic inflammation of high-risk HSCs. \nMulti-omics analysis of JMML stem cells identified several epitype-specific surface proteins as novel biomarkers for high-risk JMML. Among those factors was CD52, which has previously been described as a fetal stem cell marker. Immunotherapeutic targeting of CD52 led to reduced leukemic engraftment and increased survival in a patient-derived xenograft mouse model, providing a preclinical rationale for further assessment of a CD52-targeted treatment of high-risk JMML. \nThis study implicates oncogenic RAS signaling in the process of onco-fetal reprogramming and demonstrates how aberrantly expressed genes can be identified and leveraged for risk-stratification and the development of novel treatment strategies, as exemplified by an anti-CD52 treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007358","title":"Selective advantage of mutant stem cells in human clonal hematopoiesis is associated with attenuated response to inflammation and aging","description":"In this study we characterised the consequences of DNMT3A- and TET2-mutations in human clonal haematopoiesis. We screened 195 bone marrow samples for mutations by targeted DNA sequencing, and sequenced 99 paired peripheral blood samples to compare mutation detection between bone marrow and blood.\nWe performed single-cell analysis with TARGET-seq+ on 13 samples (4 controls and 9 clonal haematopoiesis samples), which combines single-cell genotyping for targeted mutations with whole transcriptome sequencing on FACS sorted cells. Single-cell genotyping and transcriptomes were sequenced separately and linked by common single-cell identifiers.","abstract":"In this study we characterised the consequences of DNMT3A- and TET2-mutations in human clonal haematopoiesis. We screened 195 bone marrow samples for mutations by targeted DNA sequencing, and sequenced 99 paired peripheral blood samples to compare mutation detection between bone marrow and blood.\nWe performed single-cell analysis with TARGET-seq+ on 13 samples (4 controls and 9 clonal haematopoiesis samples), which combines single-cell genotyping for targeted mutations with whole transcriptome sequencing on FACS sorted cells. Single-cell genotyping and transcriptomes were sequenced separately and linked by common single-cell identifiers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-20T14:29:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007359","title":"Molecular and immune profiles linked to androgen response categories in metastatic castration-resistant prostate cancers (mCRPC)","description":null,"abstract":"A known heterogeneous disease, prostate cancer can be broadly categorized into androgen responsive and androgen indifferent groups. Robust biomarkers to identify them and enable the development of therapeutic strategies specific to each, remain to be defined. We conducted a dynamic, modular clinical trial in which 192 men with mCRPC were segregated based on Satisfactory (≥ 50% PSA decline from baseline and &lt;5 CTC/7.5mL) vs Unsatisfactory marker status after 8-weeks of abiraterone acetate, prednisone and apalutamide (ApA). Those with Satisfactory status (n=128, 67%) were randomized to continue ApA alone (Module 2A) or with ipilimumab (Module 2B). Median overall survival (OS) and 95% CI was 46.4 (39.2, 68.2) months and 41.4 (33.3, 49.9) months respectively. Patients with Unsatisfactory marker status (n=64, 33%) had carboplatin+cabazitaxel chemotherapy added to ApA (Module 3) and had an OS and 95% CI of 18.7 (14.3, 26.3) months. Tissue availability/evaluability and defects in ≥ 2 of p53, RB1 and PTEN (also known as the aggressive variant prostate cancer molecular profile, AVPCm) in baseline tumor metastatic biopsies were associated with Unsatisfactory marker status at 8-weeks. Exploratory bulk RNA sequencing analyses revealed enrichment in the Unsatisfactory group of SPP1+ and IGFBP+ macrophages, as well as druggable myeloid cell markers. These results support the use of modular trial designs to enrich for therapeutically relevant subgroups of mCRPC, and link tumor biopsy evaluability, the AVPCm and immunosuppressive macrophage subsets to androgen indifference in mCRPC.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007360","title":"DNA methylation for the early detection of ovarian cancer in liquid biopsies","description":null,"abstract":"The plasma cell-free DNA (cfDNA) profile from ovarian cancer patients contains multiple hypermethylated patterns compared to women with benign adnexal masses. We quantified the methylation differences between diagnosed ovarian cancer patients and healthy individuals.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007361","title":"Bulk RNA-sequencing of classical monocytes from Crohn's disease patients responders and non-responders to vedolizumab","description":null,"abstract":"The goal of this project was to validate transcriptional differences between classical monocytes obtained from Crohn's disease patients that were classified as responders and non-responders to vedolizumab. PBMC samples were taken at time of response assessment.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007362","title":"Mapping the epigenomic landscape of human monocytes following innate immune activation reveals context-specific mechanisms driving endotoxin tolerance","description":"Background\nMonocytes are key mediators of innate immunity to infection, undergoing profound and dynamic changes in epigenetic state and immune function which are broadly protective but may be dysregulated in disease. Here, we aimed to advance understanding of epigenetic regulation following innate immune activation, acutely and in endotoxin tolerant states.\nMethods\nWe exposed human primary monocytes from healthy donors (n=6) to interferon-γ or differing combinations of endotoxin (lipopolysaccharide), including acute response (2hr) and two models of endotoxin tolerance: repeated stimulations (6+6hr) and prolonged exposure to endotoxin (24hr). Another subset of monocytes was left untreated (naïve). We identified context-specific regulatory elements based on epigenetic signatures for chromatin accessibility (ATAC-seq) and regulatory non-coding RNAs from total RNA sequencing.\nResults\nWe present an atlas of differential gene expression for endotoxin and interferon response, identifying widespread context specific changes. Across assayed states, only 24-29% of genes showing differential exon usage are also differential at the gene level. Overall, 19.9% (6884 of 34616) of repeatedly observed ATAC peaks were differential in at least one condition, the majority upregulated on stimulation and located in distal regions (64.1% vs 45.9% of non-differential peaks) within which sequences were less conserved than non-differential peaks. We identified enhancer-derived RNA signatures specific to different monocyte states that correlated with chromatin accessibility changes. The endotoxin tolerance models showed distinct chromatin accessibility and transcriptomic signatures, with integrated analysis identifying genes and pathways involved in the inflammatory response, detoxification, metabolism and wound healing. We leveraged eQTL mapping for the same monocyte activation states to link potential enhancers with specific genes, identifying 1,946 unique differential ATAC peaks with 1,340 expression associated genes. We further use this to inform understanding of reported GWAS, for example involving FCHO1 and coronary artery disease. \nConclusion\nThis study reports context-specific regulatory elements based on transcriptomic profiling and epigenetic signatures for enhancer-derived RNAs and chromatin accessibility in immune tolerant monocyte states, and demonstrates the informativeness of linking such elements and eQTL to inform future mechanistic studies aimed at defining therapeutic targets of immunosuppression and diseases.","abstract":"Background\nMonocytes are key mediators of innate immunity to infection, undergoing profound and dynamic changes in epigenetic state and immune function which are broadly protective but may be dysregulated in disease. Here, we aimed to advance understanding of epigenetic regulation following innate immune activation, acutely and in endotoxin tolerant states.\nMethods\nWe exposed human primary monocytes from healthy donors (n=6) to interferon-γ or differing combinations of endotoxin (lipopolysaccharide), including acute response (2hr) and two models of endotoxin tolerance: repeated stimulations (6+6hr) and prolonged exposure to endotoxin (24hr). Another subset of monocytes was left untreated (naïve). We identified context-specific regulatory elements based on epigenetic signatures for chromatin accessibility (ATAC-seq) and regulatory non-coding RNAs from total RNA sequencing.\nResults\nWe present an atlas of differential gene expression for endotoxin and interferon response, identifying widespread context specific changes. Across assayed states, only 24-29% of genes showing differential exon usage are also differential at the gene level. Overall, 19.9% (6884 of 34616) of repeatedly observed ATAC peaks were differential in at least one condition, the majority upregulated on stimulation and located in distal regions (64.1% vs 45.9% of non-differential peaks) within which sequences were less conserved than non-differential peaks. We identified enhancer-derived RNA signatures specific to different monocyte states that correlated with chromatin accessibility changes. The endotoxin tolerance models showed distinct chromatin accessibility and transcriptomic signatures, with integrated analysis identifying genes and pathways involved in the inflammatory response, detoxification, metabolism and wound healing. We leveraged eQTL mapping for the same monocyte activation states to link potential enhancers with specific genes, identifying 1,946 unique differential ATAC peaks with 1,340 expression associated genes. We further use this to inform understanding of reported GWAS, for example involving FCHO1 and coronary artery disease. \nConclusion\nThis study reports context-specific regulatory elements based on transcriptomic profiling and epigenetic signatures for enhancer-derived RNAs and chromatin accessibility in immune tolerant monocyte states, and demonstrates the informativeness of linking such elements and eQTL to inform future mechanistic studies aimed at defining therapeutic targets of immunosuppression and diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-22T09:42:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007363","title":"Towards standardized whole exome sequencing (WES) for cancer patients: lessons from a multicentric pilot study","description":"A growing number of druggable targets and national initiatives for precision oncology necessitate broader genomic profiling for many cancer patients. Whole exome sequencing (WES) offers unbiased analysis of the entire coding sequence, segmentation-based detection of copy number alterations (CNAs), and accurate determination of complex biomarkers including tumor mutational burden (TMB), homologous recombination repair deficiency (HRD), and microsatellite instability (MSI).\nTo assess the inter-institution variability of clinical WES, we performed a comparative pilot study between German Centers of Personalized Medicine (ZPMs) from five participating institutions. Tumor and matched normal DNA from 30 patients were analyzed using custom sequencing protocols and bioinformatic pipelines.\n Calling of somatic variants was highly concordant with a sensitivity between 91-95% and a positive predictive value (PPV) of 82-95% compared with a three-institution consensus and full agreement for 16 of 17 druggable targets. Deviations were observed for cases with low VAF or coverage, differing annotations, and different filter protocols. CNAs showed overall agreement in 76% for the genomic sequence with high wet-lab variability. Complex biomarkers correlated strongly between institutions (HRD: 0.79-1, TMB: 0.97-0.99) and all institutions agreed on microsatellite instability.\nThis study will contribute to the development of quality control frameworks for comprehensive genomic profiling and sheds light onto parameters that require stringent standardization.","abstract":"A growing number of druggable targets and national initiatives for precision oncology necessitate broader genomic profiling for many cancer patients. Whole exome sequencing (WES) offers unbiased analysis of the entire coding sequence, segmentation-based detection of copy number alterations (CNAs), and accurate determination of complex biomarkers including tumor mutational burden (TMB), homologous recombination repair deficiency (HRD), and microsatellite instability (MSI).\nTo assess the inter-institution variability of clinical WES, we performed a comparative pilot study between German Centers of Personalized Medicine (ZPMs) from five participating institutions. Tumor and matched normal DNA from 30 patients were analyzed using custom sequencing protocols and bioinformatic pipelines.\n Calling of somatic variants was highly concordant with a sensitivity between 91-95% and a positive predictive value (PPV) of 82-95% compared with a three-institution consensus and full agreement for 16 of 17 druggable targets. Deviations were observed for cases with low VAF or coverage, differing annotations, and different filter protocols. CNAs showed overall agreement in 76% for the genomic sequence with high wet-lab variability. Complex biomarkers correlated strongly between institutions (HRD: 0.79-1, TMB: 0.97-0.99) and all institutions agreed on microsatellite instability.\nThis study will contribute to the development of quality control frameworks for comprehensive genomic profiling and sheds light onto parameters that require stringent standardization.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-22T12:21:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007364","title":"WES sequencing of TRACERx NSCLC patient-derived xenograft models","description":"WES sequencing of TRACERx NSCLC patient-derived xenograft models","abstract":"WES sequencing of TRACERx NSCLC patient-derived xenograft models","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-22T13:42:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007365","title":"Serial TERT rearrangement breakpoint quantification in circulating tumor DNA enables minimal residual disease monitoring in patients with neuroblastoma","description":"Approximately 30% of high-risk neuroblastomas harbor genomic TERT rearrangements at diagnosis, resulting in high TERT transcript levels and active telomerase. Combined with mutations in the RAS/MAPK/ALK signaling transduction network, these patients have a dismal prognosis. Our objective was to establish a liquid biopsy-based monitoring strategy for this particularly vulnerable patient subgroup, for whom no in-time molecular diagnostic tools exist to date. Detection and quantification of TERT rearrangement breakpoints in cell-free tumor DNA circulating in peripheral blood and bone marrow plasma from patients with TERT-driven neuroblastoma improved minimal residual disease monitoring and early relapse detection in individual patients. TERT rearrangement breakpoints, as a single marker or combined with mutations in the RAS/MAPK/ALK signaling transduction network, can be reliably analyzed from 1ng DNA using droplet digital PCR assays fit for clinical routine use. TERT rearrangement breakpoints are reflected in cell-free tumor DNA and can serve as robust biomarkers for disease activity.","abstract":"Approximately 30% of high-risk neuroblastomas harbor genomic TERT rearrangements at diagnosis, resulting in high TERT transcript levels and active telomerase. Combined with mutations in the RAS/MAPK/ALK signaling transduction network, these patients have a dismal prognosis. Our objective was to establish a liquid biopsy-based monitoring strategy for this particularly vulnerable patient subgroup, for whom no in-time molecular diagnostic tools exist to date. Detection and quantification of TERT rearrangement breakpoints in cell-free tumor DNA circulating in peripheral blood and bone marrow plasma from patients with TERT-driven neuroblastoma improved minimal residual disease monitoring and early relapse detection in individual patients. TERT rearrangement breakpoints, as a single marker or combined with mutations in the RAS/MAPK/ALK signaling transduction network, can be reliably analyzed from 1ng DNA using droplet digital PCR assays fit for clinical routine use. TERT rearrangement breakpoints are reflected in cell-free tumor DNA and can serve as robust biomarkers for disease activity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-22T14:33:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007366","title":"Mesenchymal stem cells and fibroblasts underly microvascular proliferation and are associated with immunosuppression and poor outcome in glioma","description":null,"abstract":"Immunotherapies are revolutionary cancer treatments, but resistance in solid tumors such as glioma is well-established. Cancer-associated fibroblasts are emerging as important stromal elements that contribute to treatment resistance and immunosuppression. However, cancer-associated fibroblasts and their theoretical cells of origin, mesenchymal stem cells, have not been resolved at the single-cell level directly from human glioma tissue. There is evidence that mesenchymal stem cells reside in the perivascular niche. Thus, we hypothesized glioma-associated mesenchymal stem cells and fibroblasts could be found in the perivascular niche and that they contribute to local immunosuppression and pathology such as microvascular proliferation. Microvascular proliferation is a defining histopathologic feature of high-grade glioma and independent poor prognostic marker in glioma, brain metastases, and other systemic cancers. Developing targets against microvascular proliferation could lead to biomarkers and treatments to halt progression. In this study, we demonstrate that mesenchymal stem cells and fibroblasts, herein referred to as perivascular stromal cells, underly microvascular proliferation in contrast to the classical teaching it is due to endothelial cell hyperplasia. Furthermore, we capture perivascular stromal cells in a single-cell RNA velocity analysis that suggests mesenchymal stem cells are fibroblast progenitors. With signal transduction network generation and digital spatial profiling, we show these cells participate in immunosuppressive crosstalk with myeloid cell populations in the perivascular niche. Lastly, we identify a gene signature rich in extracellular matrix molecules derived from perivascular stromal cells that have undergone microvascular proliferation with implications on overall survival in glioma and five other cancers.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007367","title":"bulk TCR-seq data IMCISION","description":"We performed bulk TCR sequencing (Adaptive Biotechnologies, Seattle, WA) on peripheral blood monocytic cells (PBMCs) from 9 HNSCC patients enrolled in the IMCISION trial (Vos et al. 2021) that responded to anti-PD-1 and anti-CTLA4 combination immunotherapy. DNA was extracted from PBMCs that were isolated from pre-treatment and on-treatment blood.","abstract":"We performed bulk TCR sequencing (Adaptive Biotechnologies, Seattle, WA) on peripheral blood monocytic cells (PBMCs) from 9 HNSCC patients enrolled in the IMCISION trial (Vos et al. 2021) that responded to anti-PD-1 and anti-CTLA4 combination immunotherapy. DNA was extracted from PBMCs that were isolated from pre-treatment and on-treatment blood.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-23T11:37:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007368","title":"scRNA-seq and scTCR-seq data IMCISION","description":"We performed single cell RNA and TCR sequencing (10x Genomics) on immune infiltrates (CD45+ cells) from 18 HNSCC patients enrolled in the IMCISION trial (Vos et al. 2021). Viable immune cells were isolated from pre-treatment and on-treatment primary tumor biopsies of 10 patients responding (1 partial pathological response and 9 major pathological responses) and 7 patients non-responding to anti-PD-1 and anti-CTLA4 combination immunotherapy. One patient treated with anti-PD-1 monotherapy (1 major pathological response) was included in the dataset.","abstract":"We performed single cell RNA and TCR sequencing (10x Genomics) on immune infiltrates (CD45+ cells) from 18 HNSCC patients enrolled in the IMCISION trial (Vos et al. 2021). Viable immune cells were isolated from pre-treatment and on-treatment primary tumor biopsies of 10 patients responding (1 partial pathological response and 9 major pathological responses) and 7 patients non-responding to anti-PD-1 and anti-CTLA4 combination immunotherapy. One patient treated with anti-PD-1 monotherapy (1 major pathological response) was included in the dataset.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-23T11:38:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007369","title":"Cellular composition of spheres derived from lymph nodes of lung cancer patients","description":"To decipher the cell type composition within single spheres we performed RNA-Seq of 25 selected spheres of 4 different categories (including 8 signature-/balanced, 9 signature+/balanced, 1 signature-/aberrant, 7 signature+/aberrant). To track the individual cell types within single spheres we performed deconvolution analysis.","abstract":"To decipher the cell type composition within single spheres we performed RNA-Seq of 25 selected spheres of 4 different categories (including 8 signature-/balanced, 9 signature+/balanced, 1 signature-/aberrant, 7 signature+/aberrant). To track the individual cell types within single spheres we performed deconvolution analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-23T15:31:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007370","title":"Sclerosing Epithelioid Fibrosarcoma sequencing data","description":null,"abstract":"This study shares DNA and RNA sequencing data from SEF patients","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-23T17:04:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007371","title":"Siblings of a pancreatic adenocarcinoma patient: FPC Data Analysis","description":null,"abstract":"Genome and transcriptome sequence data from siblings of a pancreatic adenocarcinoma patient (POG_patient_28427)","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007372","title":"Mechanism of action and resistance to Trastuzumab Deruxtecan in patients with metastatic breast cancer","description":null,"abstract":"A phase II clinical trial (NCT04132960) of 179 breast cancer patients. Whole-exome sequencing is available for 110 tumor samples and 85 blood samples. The samples were collected at entry into the trial for 89 patients and upon progression for 21 patients, with 11 patients sampled at both time points.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-24T21:59:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007373","title":"High-resolution, patient-level dissection of IL-23 blockade in cutaneous psoriasis","description":"Psoriasis vulgaris and other chronic inflammatory diseases improve markedly with therapeutic blockade of IL-23 signaling in T cells, but the genetic mechanisms of response remain poorly understood. We single-cell transcriptomically profiled CD45+ immune cells isolated from lesional psoriatic skin before and after IL-23 blockade. In clinically responsive patients, a psoriatic transcriptional signature in skin-resident memory T cells was sharply attenuated. In contrast, poorly responsive patients were distinguished by enduring T17 cell activation, a mechanism distinct from alternative cytokine signaling or downstream resistance. Spatial transcriptomic analysis suggests that successful IL-23 blockade requires dampening of &gt; 90% of IL-17-induced signaling in lymphocyte-adjacent keratinocytes, an unexpectedly high threshold. We also detected a subset of persistent, disease-specific T17 abnormalities in responsive patients, revealing an irreversible cell identity that may necessitate ongoing IL-23 inhibition. Collectively, our data establishes a patient-level paradigm for dissecting response to immunomodulatory treatments.","abstract":"Psoriasis vulgaris and other chronic inflammatory diseases improve markedly with therapeutic blockade of IL-23 signaling in T cells, but the genetic mechanisms of response remain poorly understood. We single-cell transcriptomically profiled CD45+ immune cells isolated from lesional psoriatic skin before and after IL-23 blockade. In clinically responsive patients, a psoriatic transcriptional signature in skin-resident memory T cells was sharply attenuated. In contrast, poorly responsive patients were distinguished by enduring T17 cell activation, a mechanism distinct from alternative cytokine signaling or downstream resistance. Spatial transcriptomic analysis suggests that successful IL-23 blockade requires dampening of &gt; 90% of IL-17-induced signaling in lymphocyte-adjacent keratinocytes, an unexpectedly high threshold. We also detected a subset of persistent, disease-specific T17 abnormalities in responsive patients, revealing an irreversible cell identity that may necessitate ongoing IL-23 inhibition. Collectively, our data establishes a patient-level paradigm for dissecting response to immunomodulatory treatments.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-25T16:09:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007374","title":"Genome-wide DNA methylation sequencing identifies epigenetic perturbations in the upper airways under long-term exposure to moderate levels of ambient air pollution","description":"While the link between exposure to high levels of ambient particulate matter (PM) and increased incidences of respiratory and cardiovascular diseases is widely recognized, recent epidemiological studies have shown that low PM concentrations are equally associated with adverse health effects. As DNA methylation is one of the main mechanisms by which cells regulate and stabilize gene expression, changes in the methylome could constitute early indicators of dysregulated signaling pathways. So far, little is known about PM-associated DNA methylation changes in the upper airways, the first point of contact between airborne pollutants and the human body. Here, we focused on cells of the upper respiratory tract and assessed their genome-wide DNA methylation pattern to explore exposure-associated early regulatory changes. Using a mobile epidemiological laboratory, nasal lavage samples were collected from a cohort of 60 adults that lived in districts with records of low (Simmerath) or moderate (Stuttgart) PM10 levels in Germany. PM10 concentrations were verified by particle measurements on the days of the sample collection and genome-wide DNA methylation was determined by enzymatic methyl sequencing at single-base resolution. We identified 231 differentially methylated regions (DMRs) between moderately and lowly PM10 exposed individuals. A high proportion of DMRs overlapped with regulatory elements, and DMR target genes were involved in pathways regulating cellular redox homeostasis and immune response. In addition, we found distinct changes in DNA methylation of the HOXA gene cluster whose methylation levels have previously been linked to air pollution exposure but also to carcinogenesis in several instances. The findings of this study suggest that regulatory changes in upper airway cells occur at PM10 levels below current European thresholds, some of which may be involved in the development of air pollution-related diseases.","abstract":"While the link between exposure to high levels of ambient particulate matter (PM) and increased incidences of respiratory and cardiovascular diseases is widely recognized, recent epidemiological studies have shown that low PM concentrations are equally associated with adverse health effects. As DNA methylation is one of the main mechanisms by which cells regulate and stabilize gene expression, changes in the methylome could constitute early indicators of dysregulated signaling pathways. So far, little is known about PM-associated DNA methylation changes in the upper airways, the first point of contact between airborne pollutants and the human body. Here, we focused on cells of the upper respiratory tract and assessed their genome-wide DNA methylation pattern to explore exposure-associated early regulatory changes. Using a mobile epidemiological laboratory, nasal lavage samples were collected from a cohort of 60 adults that lived in districts with records of low (Simmerath) or moderate (Stuttgart) PM10 levels in Germany. PM10 concentrations were verified by particle measurements on the days of the sample collection and genome-wide DNA methylation was determined by enzymatic methyl sequencing at single-base resolution. We identified 231 differentially methylated regions (DMRs) between moderately and lowly PM10 exposed individuals. A high proportion of DMRs overlapped with regulatory elements, and DMR target genes were involved in pathways regulating cellular redox homeostasis and immune response. In addition, we found distinct changes in DNA methylation of the HOXA gene cluster whose methylation levels have previously been linked to air pollution exposure but also to carcinogenesis in several instances. The findings of this study suggest that regulatory changes in upper airway cells occur at PM10 levels below current European thresholds, some of which may be involved in the development of air pollution-related diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-26T09:30:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007375","title":"Analysis of the Elements Involved in the Enrichment of a Panel of Genomic Regions by Nanopore Sequencing Using Adaptive Sampling","description":"DNA sequencing using nanopore technologies with the affordable MinION device is useful for the identification and characterization of structural variants, long haplotypes, sequencing of repetitive regions and identification of epigenetic modifications. The main limitation of this approach is the low coverage obtained, which might be avoided by adaptive sampling, a computationally controlled method of enrichment for targeted genomic regions. This study dissects the factors involved in the enrichment by adaptive sampling of a panel of 18 human genome regions containing 20 genes implicated in breast cancer sequenced in 16 patients with familial breast cancer negative for NGS screening. An average coverage of 2.0x was obtained for the whole genome and 5.1x for selected regions. Sequencing time was the main factor improving coverage. The selection of long reads (&amp;gt;1 Kb) did not improve the enrichment. The length of the selected region, which in our study ranged from 126 to 565 Kb, did not play a significant role in enrichment. However, the region containing PMS2 showed significantly lower coverage, which could be explained by the high number of PMS2 pseudogenes (N = 14), which were also enriched. Our study shows new evidence of enrichment obtained by adaptive sampling in a panel of genomic regions and shows parameters, the relevance of sequencing time and the role of pseudogenes, that improve the enrichment yield with no library reloading or GPU use, data useful for a more efficient application of this procedure in future studies.","abstract":"DNA sequencing using nanopore technologies with the affordable MinION device is useful for the identification and characterization of structural variants, long haplotypes, sequencing of repetitive regions and identification of epigenetic modifications. The main limitation of this approach is the low coverage obtained, which might be avoided by adaptive sampling, a computationally controlled method of enrichment for targeted genomic regions. This study dissects the factors involved in the enrichment by adaptive sampling of a panel of 18 human genome regions containing 20 genes implicated in breast cancer sequenced in 16 patients with familial breast cancer negative for NGS screening. An average coverage of 2.0x was obtained for the whole genome and 5.1x for selected regions. Sequencing time was the main factor improving coverage. The selection of long reads (&amp;gt;1 Kb) did not improve the enrichment. The length of the selected region, which in our study ranged from 126 to 565 Kb, did not play a significant role in enrichment. However, the region containing PMS2 showed significantly lower coverage, which could be explained by the high number of PMS2 pseudogenes (N = 14), which were also enriched. Our study shows new evidence of enrichment obtained by adaptive sampling in a panel of genomic regions and shows parameters, the relevance of sequencing time and the role of pseudogenes, that improve the enrichment yield with no library reloading or GPU use, data useful for a more efficient application of this procedure in future studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-26T10:05:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007376","title":"RNA-Seq of RTT patient-derived cells","description":"Using a direct reprogramming method, human dermal fibroblasts from a Rett Syndrome (RTT) individual and a healthy control were used to generate neurons. RNA from fibroblasts, induced neuronal progenitor cells and neurons of patient-derived and control cells were sequenced to study the differentiation process and the differences between RTT and wildtype cells.","abstract":"Using a direct reprogramming method, human dermal fibroblasts from a Rett Syndrome (RTT) individual and a healthy control were used to generate neurons. RNA from fibroblasts, induced neuronal progenitor cells and neurons of patient-derived and control cells were sequenced to study the differentiation process and the differences between RTT and wildtype cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007377","title":"NeuroFlux_DNAseq","description":"The goal of this project is to discover suppressors and enhancers of autophagy and lysosome dysfunction in neurodegenerative disease. We will perform FACS based whole-genome CRISPR screens in human iPSC derived neurons possessing monogenic neurodegenerative mutations (Alzheimer’s, Parkinson’s and Niemann Pick disease).","abstract":"The goal of this project is to discover suppressors and enhancers of autophagy and lysosome dysfunction in neurodegenerative disease. We will perform FACS based whole-genome CRISPR screens in human iPSC derived neurons possessing monogenic neurodegenerative mutations (Alzheimer’s, Parkinson’s and Niemann Pick disease).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007378","title":"multi-region sequencing data of PDACs","description":null,"abstract":"Tumor samples were prepared under the Gastrointestinal Cancer Rapid Medical Donation Program at the Johns Hopkins Hospital, cut from frozen sections and reviewed from microdissection and H&amp;E staining in order to select ones with high cellularity. DNA extraction was done using DNeasy Blood &amp; Tissue Kits for frozen samples following the manufacturer’s guideline. Extracted DNAs were processed on an Illumina HiSeq 2500 in a paired end mode using the Agilent SureSelect V4 chemistry in the Integrated Genomics Operation (IGO) at Memorial Sloan Kettering Cancer Center (New York, NY).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007379","title":"Multi-region sequencing of PDAC patients","description":null,"abstract":"Multi-region tumor samples were cut from frozen sections or FFPEs and reviewed from microdissection and H&amp;E staining in order to select ones with high cellularity. DNA extraction was done using DNeasy Blood &amp; Tissue Kits for frozen samples following the manufacturer’s guideline. Extracted DNAs were processed on an Illumina HiSeq 2500 in a paired end mode using the Agilent SureSelect V4 chemistry in the Integrated Genomics Operation (IGO) at Memorial Sloan Kettering Cancer Center (New York, NY).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-26T22:32:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007380","title":"Separation, characterization, and identification of individuals from multi-person blood mixtures with single cell ATAC-seq","description":"We report a deconvolution and identification strategy of scATAC-seq datasets using mixed PMBCs data. After sequencing the data were processed with the de-goulash pipeline and analyzed with aim to identify and acquire biogeogrpahical ancestry of the involved individuals. The study includes samples of biological mixtures and in silico mixtures in different mixed ration and cell volumes.","abstract":"We report a deconvolution and identification strategy of scATAC-seq datasets using mixed PMBCs data. After sequencing the data were processed with the de-goulash pipeline and analyzed with aim to identify and acquire biogeogrpahical ancestry of the involved individuals. The study includes samples of biological mixtures and in silico mixtures in different mixed ration and cell volumes.","study_type":"Forensic or Paleo-genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-08T14:33:25.704467+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007381","title":"SNP array ARID1B patients","description":"SNP array ARID1B patients.\nData from PBMCs and iPSCs.","abstract":"SNP array ARID1B patients.\nData from PBMCs and iPSCs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-27T12:03:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007382","title":"NK cell dynamics in myeloma patients reveal persistent reduction of cytotoxic NK cells from diagnosis to relapse","description":"Natural killer (NK) cells mediate the cytotoxic immune response against multiple myeloma and are important effector cells in immune therapies through antibody-dependent cellular cytotoxicity. Here, we used single-cell transcriptomics, flow cytometry and functional assays to investigate the bone marrow NK cell compartment of myeloma patients at diagnosis, during treatment and after relapse. The bone marrow of myeloma patients is characterized by a reduction in conventional cytotoxic NK cells that persists throughout treatment. We show in 20% of newly diagnosed myeloma patients that an altered balance between cytotoxic and cytokine-producing NK cells translates into a reduced cytotoxic ability in response to therapeutic antibodies. The relative loss of cytotoxic NK cells persists at relapse and is accompanied by an expansion of IFN-responsive NK cells. These findings reveal previously unappreciated alterations in bone marrow NK cell composition and highlight the importance of understanding the bone marrow immune system in patients receiving immunotherapies.","abstract":"Natural killer (NK) cells mediate the cytotoxic immune response against multiple myeloma and are important effector cells in immune therapies through antibody-dependent cellular cytotoxicity. Here, we used single-cell transcriptomics, flow cytometry and functional assays to investigate the bone marrow NK cell compartment of myeloma patients at diagnosis, during treatment and after relapse. The bone marrow of myeloma patients is characterized by a reduction in conventional cytotoxic NK cells that persists throughout treatment. We show in 20% of newly diagnosed myeloma patients that an altered balance between cytotoxic and cytokine-producing NK cells translates into a reduced cytotoxic ability in response to therapeutic antibodies. The relative loss of cytotoxic NK cells persists at relapse and is accompanied by an expansion of IFN-responsive NK cells. These findings reveal previously unappreciated alterations in bone marrow NK cell composition and highlight the importance of understanding the bone marrow immune system in patients receiving immunotherapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007383","title":"Recurrent DNMT3B gene rearrangements are associated with unfavorable outcome in dicentric (9;20)-positive pediatric BCP-ALL","description":"The dicentric chromosome dic(9;20)(p11∼13;q11), occurs in 2% of pediatric acute lymphoblastic leukemia (ALL) cases. However, the prognostic significance of the dic(9;20) alterations and the mechanism in which these alterations drive leukemogenesis remains elusive. Our study describes the demographic, clinical, prognostic, and molecular characteristics of the dic(9;20)-positive ALL in a cohort of 57 pediatric BCP-ALL patients. Targeted RNA-seq and Array CGH analysis unraveled heterogeneous breakpoints on chromosomes 9 and 20 and frequent deletions of the IKZF1 gene. Together with the intrinsic susceptibility for deletions in CDKN2A, CDKN2B, and PAX5 genes in the dic(9;20)-positive ALL, these patients are eligible for treatment escalation in the AIEOP-BFM ALL 2017 clinical study. Survival analysis revealed poor 5-year event-free survival (pEFS) of 69% in dic(9;20)-positive ALL cases, compared to BCP-ALL patients enrolled in modern treatment studies. Strikingly, we identified six dic(9;20)-positive cases with rearrangements involving the DNMT3B gene, and poor 5-year pEFS of 25% (SE = 20%), compared to 79% (SE = 9%) for the remaining cohort (P = 0.011). Despite the loss of the methyltransferase domain of the DNMT3B gene in most cases with DNMT3B rearrangements, we did not observe major changes in the global methylation patterns. Differential gene expression analysis of DNMT3B-rearranged ALL unraveled a dysregulation of genes involved in hematopoiesis, lymphocyte maturation, and the PI3K/AKT signaling pathway. After confirmation in an independent cohort, DNMT3B-rearranged ALL cases should be considered high-risk for relapse and treated accordingly. \nWe provide clinical data sets of Array CGH, targeted RNA-seq, total RNA-seq, whole genome bisulfite (WGBS) and whole genome DNA sequencing (WGS) obtained from bone marrow (BM) or peripheral blood (PB) mononuclear cells of 57 pediatric patients with dicentric chromosome dic(9;20) positive Acute lymphocytic leukemia (ALL), from which in 6 cases DNMT3B gene rearrangement was identified. This data is complemented by total RNA-seq and WGBS of samples from 4 additional ALL patients with a t(12;21) translocation and ETV6-RUNX1 gene fusion. DNA was isolated from BM or PB lymphocytes using Qiagen QIAamp DNA Blood Midi Kit to perform i) Array CGH of 58 dic(9;20) positive samples by hybridizing 500ng DNA using a Agilent 400K SurePrint G3 Custom CGH Human Genome Microarray (e-Array design 84704) ii) WGBS of 6 DNMT3B rearrangement positive samples and 4 ETV6-RUNX1 positive samples using Tecan TrueMethyl oxBS-Seq module for library preparation and Illumina NovaSeq 6000 platform to run 2x151 cycles iii) WGS of DNMT3B rearrangement positive samples using Illumina Lotus DNA Library Prep Kit followed by sequencing running 2x160 cycles on an Illumina NovaSeq 6000 platform. RNA was isolated from PB lymphocytes using the PerkinElmer Chemagic 360 instrument, followed by i) targeted RNA-seq of 56 dic(9;20) positive samples prepared using Illumina TruSight RNA Pan-Cancer Panel and sequenced on an Illumina MiSeq platform running 2x75 cycles ii) total RNA-seq of 6 DNMT3B rearrangement positive samples and 4 ETV6-RUNX1 positive samples utilizing TruSeq Stranded Total RNA Library Prep Gold kit and running 2x100 cycles on an Illumina NovaSeq 6000 platform.","abstract":"The dicentric chromosome dic(9;20)(p11∼13;q11), occurs in 2% of pediatric acute lymphoblastic leukemia (ALL) cases. However, the prognostic significance of the dic(9;20) alterations and the mechanism in which these alterations drive leukemogenesis remains elusive. Our study describes the demographic, clinical, prognostic, and molecular characteristics of the dic(9;20)-positive ALL in a cohort of 57 pediatric BCP-ALL patients. Targeted RNA-seq and Array CGH analysis unraveled heterogeneous breakpoints on chromosomes 9 and 20 and frequent deletions of the IKZF1 gene. Together with the intrinsic susceptibility for deletions in CDKN2A, CDKN2B, and PAX5 genes in the dic(9;20)-positive ALL, these patients are eligible for treatment escalation in the AIEOP-BFM ALL 2017 clinical study. Survival analysis revealed poor 5-year event-free survival (pEFS) of 69% in dic(9;20)-positive ALL cases, compared to BCP-ALL patients enrolled in modern treatment studies. Strikingly, we identified six dic(9;20)-positive cases with rearrangements involving the DNMT3B gene, and poor 5-year pEFS of 25% (SE = 20%), compared to 79% (SE = 9%) for the remaining cohort (P = 0.011). Despite the loss of the methyltransferase domain of the DNMT3B gene in most cases with DNMT3B rearrangements, we did not observe major changes in the global methylation patterns. Differential gene expression analysis of DNMT3B-rearranged ALL unraveled a dysregulation of genes involved in hematopoiesis, lymphocyte maturation, and the PI3K/AKT signaling pathway. After confirmation in an independent cohort, DNMT3B-rearranged ALL cases should be considered high-risk for relapse and treated accordingly. \nWe provide clinical data sets of Array CGH, targeted RNA-seq, total RNA-seq, whole genome bisulfite (WGBS) and whole genome DNA sequencing (WGS) obtained from bone marrow (BM) or peripheral blood (PB) mononuclear cells of 57 pediatric patients with dicentric chromosome dic(9;20) positive Acute lymphocytic leukemia (ALL), from which in 6 cases DNMT3B gene rearrangement was identified. This data is complemented by total RNA-seq and WGBS of samples from 4 additional ALL patients with a t(12;21) translocation and ETV6-RUNX1 gene fusion. DNA was isolated from BM or PB lymphocytes using Qiagen QIAamp DNA Blood Midi Kit to perform i) Array CGH of 58 dic(9;20) positive samples by hybridizing 500ng DNA using a Agilent 400K SurePrint G3 Custom CGH Human Genome Microarray (e-Array design 84704) ii) WGBS of 6 DNMT3B rearrangement positive samples and 4 ETV6-RUNX1 positive samples using Tecan TrueMethyl oxBS-Seq module for library preparation and Illumina NovaSeq 6000 platform to run 2x151 cycles iii) WGS of DNMT3B rearrangement positive samples using Illumina Lotus DNA Library Prep Kit followed by sequencing running 2x160 cycles on an Illumina NovaSeq 6000 platform. RNA was isolated from PB lymphocytes using the PerkinElmer Chemagic 360 instrument, followed by i) targeted RNA-seq of 56 dic(9;20) positive samples prepared using Illumina TruSight RNA Pan-Cancer Panel and sequenced on an Illumina MiSeq platform running 2x75 cycles ii) total RNA-seq of 6 DNMT3B rearrangement positive samples and 4 ETV6-RUNX1 positive samples utilizing TruSeq Stranded Total RNA Library Prep Gold kit and running 2x100 cycles on an Illumina NovaSeq 6000 platform.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-27T15:32:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007384","title":"Genome-wide Low-depth Cell-free DNA Fragmentomics Analyses Enable Discrimination Early-stage Breast Cancers from Benign Nodules","description":null,"abstract":"In this multi-center cohort study, our objective is to develop a non-invasive liquid biopsy assay utilizing cfDNA fragmentomics low-depth WGS and machine learning for detecting early-stage BC patients among women with benign nodules (BNs). Furthermore, our study provides a combinational method of non-invasive cfDNA fragmentomics with standard image findings to improve the accuracy of early-stage BC detection, thereby reducingover-diagnosis and unnecessary biopsies in clinical practice.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007385","title":"Atypical B cells and impaired SARS-CoV-2 neutralisation following heterologous vaccination in the elderly","description":"Age is a major risk factor for hospitalization and death after SARS-CoV-2 infection, even in vaccinees. Suboptimal responses to a primary vaccination course have been reported in the elderly, but there is little information regarding the impact of age on responses to booster third doses. Here we show that individuals 70 or older who received a primary two dose schedule with AZD1222 and booster third dose with mRNA vaccine achieved significantly lower neutralizing antibody responses against SARS-CoV-2 spike pseudotyped virus compared to those below 70 at one month post booster. Neither the concentration of serum binding anti spike IgG antibody, nor the frequency of spike- specific B cells showed differences by age grouping. Impaired neutralization potency and breadth post-third dose in the elderly was associated with enrichment of circulating “atypical” spike-specific B cells expressing CD11c and FCRL5. Presence of these atypical B cells was confirmed by scRNA seq. However, when considering individuals who received three doses of mRNA vaccine, we did not observe statistically significant differences in neutralization or enrichment in atypical B cells by age grouping following dose 3. Together, our data reveal impaired neutralising antibody responses in the elderly after heterologous vaccination with AdV followed by mRNA booster dose, but not in homologous three dose mRNA vaccination highlighting that different vaccine formats differentially instruct the memory B cell response.","abstract":"Age is a major risk factor for hospitalization and death after SARS-CoV-2 infection, even in vaccinees. Suboptimal responses to a primary vaccination course have been reported in the elderly, but there is little information regarding the impact of age on responses to booster third doses. Here we show that individuals 70 or older who received a primary two dose schedule with AZD1222 and booster third dose with mRNA vaccine achieved significantly lower neutralizing antibody responses against SARS-CoV-2 spike pseudotyped virus compared to those below 70 at one month post booster. Neither the concentration of serum binding anti spike IgG antibody, nor the frequency of spike- specific B cells showed differences by age grouping. Impaired neutralization potency and breadth post-third dose in the elderly was associated with enrichment of circulating “atypical” spike-specific B cells expressing CD11c and FCRL5. Presence of these atypical B cells was confirmed by scRNA seq. However, when considering individuals who received three doses of mRNA vaccine, we did not observe statistically significant differences in neutralization or enrichment in atypical B cells by age grouping following dose 3. Together, our data reveal impaired neutralising antibody responses in the elderly after heterologous vaccination with AdV followed by mRNA booster dose, but not in homologous three dose mRNA vaccination highlighting that different vaccine formats differentially instruct the memory B cell response.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-28T09:45:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007386","title":"AT2 COPD Methylomics","description":"We generated genome-wide DNA methylation maps at single CpG resolution of primary human lung AT2 cells isolated from distal parenchyma of ex-smoker controls and COPD patients, with both mild and severe disease","abstract":"We generated genome-wide DNA methylation maps at single CpG resolution of primary human lung AT2 cells isolated from distal parenchyma of ex-smoker controls and COPD patients, with both mild and severe disease","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-28T13:34:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007387","title":"AT2 COPD Transcriptomics","description":"We generated transcriptomes of primary human lung AT2 cells isolated from distal parenchyma of ex-smoker controls and COPD patients, with both mild and severe disease.","abstract":"We generated transcriptomes of primary human lung AT2 cells isolated from distal parenchyma of ex-smoker controls and COPD patients, with both mild and severe disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-28T13:38:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007388","title":"Whole-genome sequencing of twins with Castleman disease and an unaffected sibling.","description":null,"abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007389","title":"Targeting TRIP13 in Wilms Tumor with Nuclear Export Inhibitors","description":"Wilms tumor (WT) is the most common renal malignancy of childhood. Despite improvements in the overall survival, relapse occurs in ~15% of patients with favorable histology WT (FHWT). Half of these patients will succumb to their disease. Identifying novel targeted therapies in a systematic manner remains challenging in part due to the lack of faithful preclinical in vitro models. We established ten short-term patient-derived WT cell lines and characterized these models using low-coverage whole genome sequencing, whole exome sequencing and RNA-sequencing, which demonstrated that these ex-vivo models faithfully recapitulate WT biology. We then performed targeted RNAi and CRISPR-Cas9 loss-of-function screens and identified the nuclear export genes (XPO1 and KPNB1) as strong vulnerabilities. We observed that these models are sensitive to nuclear export inhibition using the FDA approved therapeutic agent, selinexor (KPT-330). Selinexor treatment of FHWT suppressed TRIP13 expression, which was required for survival. We further identified in vitro and in vivo synergy between selinexor and doxorubicin, a chemotherapy used in high risk FHWT. Taken together, we identified XPO1 inhibition with selinexor as a potential therapeutic option to treat FHWTs and in combination with doxorubicin, leads to durable remissions in vivo.","abstract":"Wilms tumor (WT) is the most common renal malignancy of childhood. Despite improvements in the overall survival, relapse occurs in ~15% of patients with favorable histology WT (FHWT). Half of these patients will succumb to their disease. Identifying novel targeted therapies in a systematic manner remains challenging in part due to the lack of faithful preclinical in vitro models. We established ten short-term patient-derived WT cell lines and characterized these models using low-coverage whole genome sequencing, whole exome sequencing and RNA-sequencing, which demonstrated that these ex-vivo models faithfully recapitulate WT biology. We then performed targeted RNAi and CRISPR-Cas9 loss-of-function screens and identified the nuclear export genes (XPO1 and KPNB1) as strong vulnerabilities. We observed that these models are sensitive to nuclear export inhibition using the FDA approved therapeutic agent, selinexor (KPT-330). Selinexor treatment of FHWT suppressed TRIP13 expression, which was required for survival. We further identified in vitro and in vivo synergy between selinexor and doxorubicin, a chemotherapy used in high risk FHWT. Taken together, we identified XPO1 inhibition with selinexor as a potential therapeutic option to treat FHWTs and in combination with doxorubicin, leads to durable remissions in vivo.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-28T21:35:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007390","title":"Single cell landscape of Multicentric Castleman Disease in monozygotic twins","description":null,"abstract":"Idiopathic Multicentric Castleman Disease (iMCD) is a rare IL-6-driven hematological disorder characterized by systemic lymphadenopathy, elevated immunoglobulin levels, and prominent plasmacytosis in the bone marrow and lymph nodes. Here, we present an unusual occurrence of iMCD in identical twins. Using single cell sequencing, we identified nodal endothelial cells and fibroblastic reticular cells as the source of IL-6 signals. An “inflammatory” peripheral monocytosis enriched for the expression of S100A family genes was evident in both twins, as well as a group of monocytes expressing cytotoxic gene signatures in the affected twin with milder clinical manifestations.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-29T17:14:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007391","title":"Dissecting_the_Genetic_basis_of_Melioidosis_Infection","description":"Melioidosis is a neglected tropical infectious disease caused by a soil bacterium Burkholderia pseudomallei. In Thailand, it is the leading cause of sepsis and the mortality of melioidosis is 40%. Diabetes mellitus (DM) is a major comorbidity with more than half of melioidosis cases being diabetic. There are interesting interactions between diabetic status, susceptibility to melioidosis and outcome that require additional investigation. Melioidosis displays broad clinical manifestations with severity ranging from skin abscesses to severe sepsis and death. Current diagnostic testing relies on blood culture which usually takes up to 4 days, a stage by which approximately 20% of all melioidosis cases undergo septic shock and become fatal. Funded by Wellcome Trust, we have established a cohort of melioidosis patients (n= 549), as well as healthy controls (n = 506) and other infection controls (n= 190) from the same population in Thailand. The cohort combines the unusual combination of host and pathogen samples to allow multi-omic data generation and the identification of interactions between them. We have already generated bulk RNA-sequencing data for  1030 participants, which is currently undergoing analysis in collaboration with the Davenport group from the Sanger Human Genetic department. In this preliminary analysis, we have identified differential gene expression signatures between survivors and non-survivors. Through a collaboration with Dr Davenport, we are in the process of conducting whole genome sequencing (15X WGS) for a subset of the cohort (n = 560). This will help us address the role of genetic variation in driving the observed differences in gene expression between survivors and non-survivors. In addition to this, we also aim to identify the interactions between host and pathogen variants, as well as their influence on host transcriptomic response to melioidosis. A generation of 15x WGS on the remaining 658 individuals will maximise power to detect the pathogen-host interactions across the cohort.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Melioidosis, a deadly infectious disease prevalent in Thailand is caused by an environmental bacterium Burkholderia pseudomallei. We established a cohort of 549 melioidosis patients, 506 healthy controls, and 190 infection controls from individuals living in the disease endemic area to investigate the interplay between host and pathogen. Preliminary analysis of bulk RNA-sequencing data from 1,030 participants from the cohort has revealed gene expression signatures distinguishing survivors from non-survivors. Through collaboration with the Davenport group (Human Genomics), we are conducting whole genome sequencing (15x) on a subset of 560 individuals to explore the role of genetic variation. By performing additional 15x WGS on the remaining 658 participants, we will maximise the detection of pathogen-host interactions. This will ultimately result in better understanding of the melioidosis susceptibility and outcomes.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007392","title":"RCC_subclonality_by_targeted_nanoseq","description":"This study uses duplex sequencing to explore subclonal selection in RCC, to answer whether selection is confined by either previous genomic events or the microenvironment.","abstract":"Targeted duplex sequencing is used to explore subclonality in kidney cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007393","title":"Efficacy of nivolumab in pediatric cancers with high mutation burden and mismatch-repair deficiency","description":"Purpose: Checkpoint-inhibitors have limited efficacy for children with unselected solid and brain tumors. We report the first prospective pediatric trial (NCT02992964) using nivolumab exclusively for refractory non-hematological cancers harboring tumor mutation burden (TMB) ≥5 mutations/megabase (mut/Mb) and/or mismatch-repair deficiency (MMRD).\n\nPatients and methods: Twenty patients were screened, and ten ultimately included in the response cohort of whom nine had TMB &gt;10mut/Mb (three initially eligible based on MMRD) and one patient had TMB between 5-10 mut/Mb.\n\nResults: Delayed immune responses contributed to best overall response of 50%, improving on initial objective responses (20%) and leading to 2-year overall survival (OS) of 50% (95% CI; 27, 93). Four children, including three with refractory malignant gliomas are in complete remission at a median follow-up of 37-months (range: 32.4-60), culminating in 2-year OS of 43% (95% CI; 18.2, 100). Biomarker analyses confirmed benefit in children with germline MMRD, microsatellite instability, higher activated and lower regulatory circulating T-cells. Stochastic mutation accumulation driven by underlying germline MMRD impacted the tumor microenvironment, contributing to delayed responses. No benefit was observed in the single patient with a MMR-proficient tumour and TMB 7.4 mut/Mb.\n\nConclusions: Nivolumab resulted in durable responses and prolonged survival for the first time in a pediatric trial of refractory hypermutated cancers including malignant gliomas. Novel biomarkers identified here need to be translated rapidly to clinical care to identify children who can benefit from checkpoint-inhibitors, including for upfront management of their cancers.","abstract":"Purpose: Checkpoint-inhibitors have limited efficacy for children with unselected solid and brain tumors. We report the first prospective pediatric trial (NCT02992964) using nivolumab exclusively for refractory non-hematological cancers harboring tumor mutation burden (TMB) ≥5 mutations/megabase (mut/Mb) and/or mismatch-repair deficiency (MMRD).\n\nPatients and methods: Twenty patients were screened, and ten ultimately included in the response cohort of whom nine had TMB &gt;10mut/Mb (three initially eligible based on MMRD) and one patient had TMB between 5-10 mut/Mb.\n\nResults: Delayed immune responses contributed to best overall response of 50%, improving on initial objective responses (20%) and leading to 2-year overall survival (OS) of 50% (95% CI; 27, 93). Four children, including three with refractory malignant gliomas are in complete remission at a median follow-up of 37-months (range: 32.4-60), culminating in 2-year OS of 43% (95% CI; 18.2, 100). Biomarker analyses confirmed benefit in children with germline MMRD, microsatellite instability, higher activated and lower regulatory circulating T-cells. Stochastic mutation accumulation driven by underlying germline MMRD impacted the tumor microenvironment, contributing to delayed responses. No benefit was observed in the single patient with a MMR-proficient tumour and TMB 7.4 mut/Mb.\n\nConclusions: Nivolumab resulted in durable responses and prolonged survival for the first time in a pediatric trial of refractory hypermutated cancers including malignant gliomas. Novel biomarkers identified here need to be translated rapidly to clinical care to identify children who can benefit from checkpoint-inhibitors, including for upfront management of their cancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-06-30T20:35:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007394","title":"Copy numbers in resectable gastric cancer treated with surgery alone","description":"Purpose: Gastric cancer is a heterogeneous disease requiring stratification to recognize its underlying biology and variable clinical outcome. The Cancer Genome Atlas (TCGA) recognizes four molecular subgroups: Epstein-Barr virus positive (EBV+) and microsatellite instable (MSI) with superior survival compared to genomically stable (GS) and chromosomal instable (CIN). Since classification criteria to distinguish GS from CIN were not defined, alternative markers such as Lauren’s histopathology or CDH1/p53 immunohistochemistry are commonly applied. Here we compared survival of gastric cancer subgroups determined by four methods.\nExperimental Design: EBV- and microsatellite stable tumors from a total of 309 patients treated with surgery alone were assigned to subgroups by: (i) specific copy number aberrations as determined by TCGA (GS or CIN), (ii) genome instability index (GII; high or low), (iii) Lauren’s classification (diffuse or intestinal), and (iv) CDH1/p53 immunohistochemistry (IHC; aberrant CDH1, normal-, or aberrant p53 expression). Subgroups were associated with cancer-related survival (CRS).\nResults: Five-year CRS was 42.0% for diffuse and 49.5% for intestinal type tumors, and 57.8% for GS and 41.6% for CIN tumors. Classification by GII or CDH1/p53 IHC did not correlate with CRS. The combination of TCGA and Lauren classifications resulted in four distinct subgroups. Five-year CRS for GS-intestinal (n=24), GS-diffuse (n=57), CIN-intestinal (n=142) and CIN-diffuse (n=86) was 61.4%, 56.5%, 47.6%, and 31.5%, respectively.\nConclusions: TCGA’s GS and CIN have additional prognostic value to Lauren’s diffuse and intestinal subgroups in gastric cancer. GS-intestinal, GS-diffuse, CIN-intestinal and CIN-diffuse constitute biologically distinct entities and are suggested as stratification variables for future studies.","abstract":"Purpose: Gastric cancer is a heterogeneous disease requiring stratification to recognize its underlying biology and variable clinical outcome. The Cancer Genome Atlas (TCGA) recognizes four molecular subgroups: Epstein-Barr virus positive (EBV+) and microsatellite instable (MSI) with superior survival compared to genomically stable (GS) and chromosomal instable (CIN). Since classification criteria to distinguish GS from CIN were not defined, alternative markers such as Lauren’s histopathology or CDH1/p53 immunohistochemistry are commonly applied. Here we compared survival of gastric cancer subgroups determined by four methods.\nExperimental Design: EBV- and microsatellite stable tumors from a total of 309 patients treated with surgery alone were assigned to subgroups by: (i) specific copy number aberrations as determined by TCGA (GS or CIN), (ii) genome instability index (GII; high or low), (iii) Lauren’s classification (diffuse or intestinal), and (iv) CDH1/p53 immunohistochemistry (IHC; aberrant CDH1, normal-, or aberrant p53 expression). Subgroups were associated with cancer-related survival (CRS).\nResults: Five-year CRS was 42.0% for diffuse and 49.5% for intestinal type tumors, and 57.8% for GS and 41.6% for CIN tumors. Classification by GII or CDH1/p53 IHC did not correlate with CRS. The combination of TCGA and Lauren classifications resulted in four distinct subgroups. Five-year CRS for GS-intestinal (n=24), GS-diffuse (n=57), CIN-intestinal (n=142) and CIN-diffuse (n=86) was 61.4%, 56.5%, 47.6%, and 31.5%, respectively.\nConclusions: TCGA’s GS and CIN have additional prognostic value to Lauren’s diffuse and intestinal subgroups in gastric cancer. GS-intestinal, GS-diffuse, CIN-intestinal and CIN-diffuse constitute biologically distinct entities and are suggested as stratification variables for future studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-02T18:30:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007395","title":"An analysis of enhancer-promoter connectivity alterations","description":null,"abstract":"The study uncovers epigenomic changes associated with dexamethasone response heterogeneity in myeloma cells, revealing rewired promoter-enhancer interactions and DNA loop stabilization","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007396","title":"Evaluation of somatic mutations in urine samples as a non-invasive method for the detection and molecular classification of endometrial cancer","description":"Purpose: Current diagnostic methods for endometrial cancer lack specificity, leading to many women undergoing invasive procedures. The aim of this study was to evaluate somatic mutations in urine to accurately discriminate endometrial cancer patients from controls.\nExperimental Design: Overall, 72 samples were analyzed using next-generation sequencing with molecular identifiers targeting 47 genes. We evaluated urine supernatant samples from women with endometrial cancer (n=19) and age-matched controls (n=20). Cell pellets from urine and plasma samples from seven cases were sequenced; further, we also evaluated paired tumor samples from all cases. Finally, immunohistochemical markers for molecular profiling were evaluated in all tumor samples.\nResults: Overall, we were able to identify mutations in DNA from urine supernatant samples in 100% of endometrial cancers. In contrast, only one control (5%) showed variants at a variant allele frequency (VAF)≥2% in the urine supernatant samples. The molecular classification obtained by using tumor samples and urine samples showed good agreement. Analyses in paired samples revealed a higher number of mutations and VAFs in urine supernatants than in urine cell pellets and blood samples.\nConclusions: Evaluation of somatic mutations using urine samples may offer a user-friendly and reliable tool for endometrial cancer detection and molecular classification. The diagnostic performance for endometrial cancer detection was very high, and cases could be molecularly classified using these noninvasive and self-collected samples. Additional multi-center evaluations using larger sample sizes are needed to validate the results and understand the potential of urine samples for the early detection and prognosis of endometrial cancer.","abstract":"Purpose: Current diagnostic methods for endometrial cancer lack specificity, leading to many women undergoing invasive procedures. The aim of this study was to evaluate somatic mutations in urine to accurately discriminate endometrial cancer patients from controls.\nExperimental Design: Overall, 72 samples were analyzed using next-generation sequencing with molecular identifiers targeting 47 genes. We evaluated urine supernatant samples from women with endometrial cancer (n=19) and age-matched controls (n=20). Cell pellets from urine and plasma samples from seven cases were sequenced; further, we also evaluated paired tumor samples from all cases. Finally, immunohistochemical markers for molecular profiling were evaluated in all tumor samples.\nResults: Overall, we were able to identify mutations in DNA from urine supernatant samples in 100% of endometrial cancers. In contrast, only one control (5%) showed variants at a variant allele frequency (VAF)≥2% in the urine supernatant samples. The molecular classification obtained by using tumor samples and urine samples showed good agreement. Analyses in paired samples revealed a higher number of mutations and VAFs in urine supernatants than in urine cell pellets and blood samples.\nConclusions: Evaluation of somatic mutations using urine samples may offer a user-friendly and reliable tool for endometrial cancer detection and molecular classification. The diagnostic performance for endometrial cancer detection was very high, and cases could be molecularly classified using these noninvasive and self-collected samples. Additional multi-center evaluations using larger sample sizes are needed to validate the results and understand the potential of urine samples for the early detection and prognosis of endometrial cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-03T13:21:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007397","title":"scRNAsequencing of in vitro expanded limbal stem cells of aniridia donors","description":"Identifying potential heterogeneity and expression differences within Aniridia limbal stem cells.","abstract":"Identifying potential heterogeneity and expression differences within Aniridia limbal stem cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-04T07:54:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007398","title":"Total RNA sequencing from the TNT trial (NCT00532727)","description":"Primary tumours from 186 TNT participants (13 matched recurrences) were profiled using total RNA-sequencing. Four transcriptional DDR-related and 25 immune-related signatures were evaluated. We assessed their association with objective-response-rate (ORR) and progression-free-survival (PFS) and performed conditional inference forest clustering to integrate multi-modal data.","abstract":"Primary tumours from 186 TNT participants (13 matched recurrences) were profiled using total RNA-sequencing. Four transcriptional DDR-related and 25 immune-related signatures were evaluated. We assessed their association with objective-response-rate (ORR) and progression-free-survival (PFS) and performed conditional inference forest clustering to integrate multi-modal data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-04T09:50:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007399","title":"shallow WGS and deep targeted panel on ctDNA in rhabdomyosarcomas","description":"The genomic spectrum of rhabdomyosarcoma (RMS) progression from primary to relapse is not fully understood. In this study we investigate 35 patients with relapsed RMS from two contributing institutions, 18 fusion-positive (FP-RMS) and 17 fusion-negative RMS (FN-RMS). Targeted DNA or whole exome sequencing (WES) was used to detect alterations in paired primary/relapsed samples. In 10 cases, circulating tumor DNA (ctDNA) from multiple timepoints through clinical care and progression was analyzed for feasibility of liquid biopsy in monitoring treatment response/relapse. ctDNA alterations were evaluated using a targeted custom RMS panel (36 genes) at high coverage for single nucleotide variation and fusion detection, and a shallow whole genome sequencing for copy number variation. FP-RMS had a stable genome with relapse, with the most common secondary alterations : CDKN2A/B, MYCN and CDK4 alterations, being already present at diagnosis and impacting overall survival. FP-RMS lacking major secondary events at baseline acquired recurrent MYCN and AKT1 alterations. FN-RMS acquired a higher number of new alterations, most commonly SMARCA2 missense mutations. ctDNA analyses detected pathognomonic variants in all RMS patients at diagnosis, regardless of FP/FN or type of alterations, while at relapse selected alterations were confirmed in 86% of FP-RMS and 100% FN-RMS. Moreover, a higher number of fusion reads was detected with increased disease burden and at relapse in patients following a fatal outcome. These results underscore patterns of tumor progression within a relatively stable genomic landscape and provide rationale for using liquid biopsy to monitor treatment response.","abstract":"The genomic spectrum of rhabdomyosarcoma (RMS) progression from primary to relapse is not fully understood. In this study we investigate 35 patients with relapsed RMS from two contributing institutions, 18 fusion-positive (FP-RMS) and 17 fusion-negative RMS (FN-RMS). Targeted DNA or whole exome sequencing (WES) was used to detect alterations in paired primary/relapsed samples. In 10 cases, circulating tumor DNA (ctDNA) from multiple timepoints through clinical care and progression was analyzed for feasibility of liquid biopsy in monitoring treatment response/relapse. ctDNA alterations were evaluated using a targeted custom RMS panel (36 genes) at high coverage for single nucleotide variation and fusion detection, and a shallow whole genome sequencing for copy number variation. FP-RMS had a stable genome with relapse, with the most common secondary alterations : CDKN2A/B, MYCN and CDK4 alterations, being already present at diagnosis and impacting overall survival. FP-RMS lacking major secondary events at baseline acquired recurrent MYCN and AKT1 alterations. FN-RMS acquired a higher number of new alterations, most commonly SMARCA2 missense mutations. ctDNA analyses detected pathognomonic variants in all RMS patients at diagnosis, regardless of FP/FN or type of alterations, while at relapse selected alterations were confirmed in 86% of FP-RMS and 100% FN-RMS. Moreover, a higher number of fusion reads was detected with increased disease burden and at relapse in patients following a fatal outcome. These results underscore patterns of tumor progression within a relatively stable genomic landscape and provide rationale for using liquid biopsy to monitor treatment response.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-04T10:27:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007400","title":"Genome-wide cell-free DNA biological patterns in patients with cancer","description":"The structure of cell-free DNA (cfDNA) is altered in the blood of cancer patients. From whole genome sequencing we retrieved the cfDNA fragment-end composition using a new software (FrEIA), as well as the cfDNA size and tumor fraction in three independent cohorts (n=925 cancer from &gt;10 types and 321 control samples). At 95% specificity, we detect 72% of cancer samples using at least one cfDNA measure, including 64% of early-stage cancer (n=220). cfDNA detection correlates with a shorter overall (p=0.018) and recurrence-free (p=0.006) survival in patients with resectable esophageal adenocarcinoma. Integrating cfDNA measures with machine learning in an independent test set (n=396 cancer, 90 controls) achieve a detection accuracy of 82% and AUROC of 96%. In conclusion, harnessing the biological features of cfDNA can improve at no-extra cost the diagnostic performance of liquid biopsies.","abstract":"The structure of cell-free DNA (cfDNA) is altered in the blood of cancer patients. From whole genome sequencing we retrieved the cfDNA fragment-end composition using a new software (FrEIA), as well as the cfDNA size and tumor fraction in three independent cohorts (n=925 cancer from &gt;10 types and 321 control samples). At 95% specificity, we detect 72% of cancer samples using at least one cfDNA measure, including 64% of early-stage cancer (n=220). cfDNA detection correlates with a shorter overall (p=0.018) and recurrence-free (p=0.006) survival in patients with resectable esophageal adenocarcinoma. Integrating cfDNA measures with machine learning in an independent test set (n=396 cancer, 90 controls) achieve a detection accuracy of 82% and AUROC of 96%. In conclusion, harnessing the biological features of cfDNA can improve at no-extra cost the diagnostic performance of liquid biopsies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-04T10:42:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007401","title":"Seq-ing the SINEs of Central Nervous System Tumors in Cerebrospinal Fluid","description":"It is often challenging to distinguish cancerous from non-cancerous lesions in the brain using conventional diagnostic approaches. We introduce an analytic technique called Real-CSF to detect cancers of the central nervous system from evaluation of DNA in the cerebrospinal fluid (CSF). Short interspersed nuclear elements (SINEs) are PCR-amplified with a single primer pair and the PCR products are evaluated by next generation sequencing. Real-CSF assesses genome wide copy number alterations as well as focal amplifications of selected oncogenes.  Real-CSF was applied to 280 CSF samples and correctly identified 67% of 184 cancers and 96% of 96 non-cancerous brain lesions.  CSF analysis was considerably more sensitive than standard of care cytology and plasma cell-free DNA analysis in the same patients.  Real-CSF therefore has the capacity to be used in combination with other clinical, radiologic, and laboratory-based data to inform the diagnosis and management of patients with suspected cancers of the brain.","abstract":"It is often challenging to distinguish cancerous from non-cancerous lesions in the brain using conventional diagnostic approaches. We introduce an analytic technique called Real-CSF to detect cancers of the central nervous system from evaluation of DNA in the cerebrospinal fluid (CSF). Short interspersed nuclear elements (SINEs) are PCR-amplified with a single primer pair and the PCR products are evaluated by next generation sequencing. Real-CSF assesses genome wide copy number alterations as well as focal amplifications of selected oncogenes.  Real-CSF was applied to 280 CSF samples and correctly identified 67% of 184 cancers and 96% of 96 non-cancerous brain lesions.  CSF analysis was considerably more sensitive than standard of care cytology and plasma cell-free DNA analysis in the same patients.  Real-CSF therefore has the capacity to be used in combination with other clinical, radiologic, and laboratory-based data to inform the diagnosis and management of patients with suspected cancers of the brain.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007402","title":"Single-cell multi-omics defines the cell-type-specific impact of splicing aberrations in human hematopoietic clonal outgrowths","description":null,"abstract":"RNA splicing factors are recurrently mutated in clonal blood disorders, but understanding the impact of dysregulated splicing in hematopoiesis remains challenging. To overcome technical limitations, we integrated Genotyping of Transcriptomes (GoT) with long-read single-cell transcriptome profiling and proteogenomics for single-cell profiling of transcriptomes, surface proteins, somatic mutations, and RNA splicing (GoT-Splice). We applied GoT-Splice to bone marrow progenitors from myelodysplastic syndrome (MDS) patients with mutations int core splicing factor SF3B1. SF3B1mut cells were enriched in the megakaryocytic-erythroid lineage, with expansion of SF3B1mut erythroid progenitor cells. We uncovered distinct cryptic 3’ splice site usage across progenitor populations and stage-specific aberrant splicing during erythroid differentiation. Profiling SF3B1-mutated clonal hematopoiesis samples revealed that erythroid lineage bias and cell-type specific cryptic 3’ splice site usage in SF3B1mut cells precede overt MDS. Collectively, GoT-Splice defines cell-type specific impacts of somatic mutations on RNA splicing, from early clonal outgrowths to overt neoplasia, directly in human samples.","study_type":"Cancer Genomics","pubmed_ids":[37582363],"external_links":null,"is_released":true,"released_date":"2023-07-05T19:32:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007403","title":"checup","description":"Sequencing data from a phase II study of nivolumab and ipilimumab in recurrent or refractory cancer of unknown primary (CheCUP trial)","abstract":"Sequencing data from a phase II study of nivolumab and ipilimumab in recurrent or refractory cancer of unknown primary (CheCUP trial)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-06T09:11:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007404","title":"Genomic and immune signatures predict clinical outcome in newly diagnosed multiple myeloma treated with immunotherapy regimens","description":null,"abstract":"Despite improving outcomes, 40% of patients with newly diagnosed multiple myeloma (NDMM) treated with daratumumab, an CD38-targeted monoclonal antibody, progress prematurely. By integrating tumor whole genome (WGS) and microenvironment single-cell RNA sequencing from upfront phase-II trials using carfilzomib, lenalidomide and dexamethasone with/without daratumumab (DKRd) (NCT03290950 and NCT02937571), we show how distinct genomic drivers including high APOBEC mutational activity, deletion of IKFZ3, TENT5C, RPL5, and gain(8q) impact clinical outcomes. Furthermore, the evaluation of paired-marrow profiles, taken before and after eight cycles of DKRd, shows that the NK-cells before treatment, disappearance of sustained immune activation (i.e., B-cell and T-cells), and monocyte expansion over time is predictive of sustained minimal residual disease negativity. Overall, this study shows that there is a complex interplay between tumor cells and immune microenvironment which is predictive of clinical outcome and the depth of treatment response in NDMM treated with CD38-targeted monoclonal antibody.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-06T09:46:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007405","title":"Cohesin Mutations in AML","description":"Cohesin shapes the nuclear chromatin architecture, including enhancer-promoter interactions,\nand its components, of which especially STAG2 and RAD21, are frequently mutated in myeloid\nmalignancies. To elucidate mechanisms of leukemogenesis associated with cohesin mutations\nin humans, we comprehensively characterized genetic, epigenetic, transcriptional, and\nchromatin conformational changes in acute myeloid leukemia (AML). To corroborate our\nfindings, we performed complementary siRNA-mediated depletion of STAG2, its paralogue\nSTAG1 or RAD21 in cord blood-derived CD34+ primary human hematopoietic stem and\nprogenitor cells (HSPCs). We show that STAG2 mutations consistently lead to the loss of\nSTAG2 protein and are associated with a specific set of co-occurring mutations, while STAG1\nwas never mutated in AML. Loss of STAG2 was frequently compensated by STAG1. Still,\nspecific loci displayed altered cohesin occupancy, gene expression and corresponding changes\nin local chromatin activation as measured by H3K27ac enrichment and chromatin accessibility.\nHigh-throughput chromosome conformation capture (in-situ Hi-C) revealed significantly\naltered chromatin looping in cohesin-mutated AMLs, including weakened enhancer-promoter\ncontacts with reduced, cohesin-dependent promoter activity. In HSPCs, we detected\ntranscriptomic and epigenetic effects overlapping STAG2-mutant AML-specific changes\nfollowing STAG2 knockdown (KD), that were not invoked by the depletion of STAG1. We\nalso found that STAG2 loss in cultured HSPCs impaired the differentiation capacity, especially\nerythroid colony formation which maintained HSPC-like gene expression. This work\nestablishes STAG2 as a key regulator of cohesin-associated chromatin architecture, gene\nexpression and differentiation in the human hematopoietic system and identifies candidate\ntarget genes that may be implicated in leukemogenesis.","abstract":"Cohesin shapes the nuclear chromatin architecture, including enhancer-promoter interactions,\nand its components, of which especially STAG2 and RAD21, are frequently mutated in myeloid\nmalignancies. To elucidate mechanisms of leukemogenesis associated with cohesin mutations\nin humans, we comprehensively characterized genetic, epigenetic, transcriptional, and\nchromatin conformational changes in acute myeloid leukemia (AML). To corroborate our\nfindings, we performed complementary siRNA-mediated depletion of STAG2, its paralogue\nSTAG1 or RAD21 in cord blood-derived CD34+ primary human hematopoietic stem and\nprogenitor cells (HSPCs). We show that STAG2 mutations consistently lead to the loss of\nSTAG2 protein and are associated with a specific set of co-occurring mutations, while STAG1\nwas never mutated in AML. Loss of STAG2 was frequently compensated by STAG1. Still,\nspecific loci displayed altered cohesin occupancy, gene expression and corresponding changes\nin local chromatin activation as measured by H3K27ac enrichment and chromatin accessibility.\nHigh-throughput chromosome conformation capture (in-situ Hi-C) revealed significantly\naltered chromatin looping in cohesin-mutated AMLs, including weakened enhancer-promoter\ncontacts with reduced, cohesin-dependent promoter activity. In HSPCs, we detected\ntranscriptomic and epigenetic effects overlapping STAG2-mutant AML-specific changes\nfollowing STAG2 knockdown (KD), that were not invoked by the depletion of STAG1. We\nalso found that STAG2 loss in cultured HSPCs impaired the differentiation capacity, especially\nerythroid colony formation which maintained HSPC-like gene expression. This work\nestablishes STAG2 as a key regulator of cohesin-associated chromatin architecture, gene\nexpression and differentiation in the human hematopoietic system and identifies candidate\ntarget genes that may be implicated in leukemogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-06T13:15:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007406","title":"Whole genome sequencing of individuals from Latvia: the first step towards the population-specific reference of genetic variation","description":null,"abstract":"Understanding the extent of human genetic variation through whole genome sequencing (WGS) is limited by the scarce availability of genome sequences from underrepresented populations, even within Europe. Latvia represents a population with the highest degree of Western-European hunter-gatherer genetic ancestry and additional genetic data from Latvia has a potential to improve genomics research globally. To address this issue, we utilised the MGI DNBSEQTM platform to sequence 502 individuals from the Genome Database of Latvian Population as representatives of the Latvian population. Here we present a high-coverage WGS dataset, which allowed us to identify more than 19 million variants, of which 3.3% are not represented in gnomAD and dbSNP databases. We provide a detailed assessment of variant type, location, function, medical relevance and novelty of identified genetic variants. Principal component analysis (PCA) shows the clustering of the Latvian population inside the European sample, but distinct from other 1000G European populations. Additionally, we constructed a population-specific reference panel and compared its performance in imputation with the 1000G dataset. Our findings demonstrate that the Latvian population-specific reference panel performs better for common and low-frequency variants, both in terms of total count and accuracy, when compared to 1000G panel. In summary, our study provides the first data for a regional reference genome that will serve as a cornerstone for the development of precision medicine and will complement the global genome dataset to improve understanding of human genetic variation.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007407","title":"WGS_non_malignant_colon_and_colorectal_cancer","description":"The incidence of early onset colorectal cancer (eoCRC) has been increasing over the last few decades. Results from the whole genome sequencing of 982 colorectal cancers in the Mutographs study have identified several mutational signatures associated with the microbiome, including the COSMIC reference signature SBS88. This signature is caused by exposure to Colibactin, a toxin produced by strains of Escherichia Coli which carry the pks pathogenicity island. The mutation burden of SBS88 was positively correlated with the age standardised rate (ASR) of CRC and was significantly more frequent in eoCRC. In addition, previous studies of the normal colon have shown that colibactin exposure likely occurs within the first decade of life. These results together suggest that the microbiome is contributing to the increase in eoCRC, and that it might be possible to assess the risk of eoCRC and/or control eoCRC incidence by monitoring the gut microbiome. This study aims to sequence both colorectal cancer and non-malignant colon to establish whether there is a causal relationship between colibactin exposure and eoCRC.","abstract":"The incidence of early onset colorectal cancer (eoCRC) has been increasing over the last few decades. Results from the whole genome sequencing of 982 colorectal cancers in the Mutographs study have identified several mutational signatures associated with the microbiome, including the COSMIC reference signature SBS88. This signature is caused by exposure to Colibactin, a toxin produced by strains of Escherichia Coli which carry the pks pathogenicity island. The mutation burden of SBS88 was positively correlated with the age standardised rate (ASR) of CRC and was significantly more frequent in eoCRC. In addition, previous studies of the normal colon have shown that colibactin exposure likely occurs within the first decade of life. These results together suggest that the microbiome is contributing to the increase in eoCRC, and that it might be possible to assess the risk of eoCRC and/or control eoCRC incidence by monitoring the gut microbiome. This study aims to sequence both colorectal cancer and non-malignant colon to establish whether there is a causal relationship between colibactin exposure and eoCRC.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007408","title":"Spatial transcriptomics in triple negative breast cancer","description":null,"abstract":"Intratumoral heterogeneity (ITH) is one of the leading drivers of therapeutic resistance and is associated with poor survival (Jamal-Hanjani et al, Clin Can Res 2015; doi:10.1200/JCO.2011.39.5624, doi:10.1093/jnci/djr545, doi:10.1038/nm.3886, doi:10.1093/annonc/mdy024). While Ttriple negative breast cancer (TNBC) is known to be highly heterogeneous, both at the genomic and transcriptomic levels, . Sspatial information on the tumortumour  organization and cell composition in TNBC is lacking. Here, we investigated TNBC tumortumour architecture including its microenvironment using spatial transcriptomics on a series of 94 TNBC samples. Following a pure histomorphological characterization of the samples, spatial expression deconvolution of the histomorphological compartments was performed for an in-depth characterization description of the tumortumour and stroma organization and composition of each TNBC molecular subtype. Furthermore, a detailed molecular characterization of tertiary lymphoid structures (TLS) led to the identification of a gene signatures shown to be strongly associated to disease outcome and response to immunotherapy in several tumortumour types beyond TNBC. A stepwise clustering analysis identified nine distinct TNBC ecotypes, further validated in external datasets. Several ecotypes were associated with disease outcome and characterized by potentially actionable features. This is the largest TNBC series providing a comprehensive insight into the complexity of TNBC ecosystem with potential clinical relevance, opening avenues for the tailoring of treatments tailoring including immunotherapy.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007409","title":"Diagnosis of multisystem inflammatory syndrome in children by a whole-blood transcriptional signature","description":"To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki Disease (KD), bacterial infections and viral infections.\nChildren presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020-April 2021 were prospectively recruited. Whole blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C to those from children with KD, definite bacterial and viral infections. Data deposited here comprises samples from patients recruited into the DIAMONDS study.","abstract":"To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki Disease (KD), bacterial infections and viral infections.\nChildren presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020-April 2021 were prospectively recruited. Whole blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C to those from children with KD, definite bacterial and viral infections. Data deposited here comprises samples from patients recruited into the DIAMONDS study.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-06T15:47:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007410","title":"Nanoseq_non_malignant_colon_and_colorectal_cancer","description":"The incidence of early onset colorectal cancer (eoCRC) has been increasing over the last few decades. Results from the whole genome sequencing of 982 colorectal cancers in the Mutographs study have identified several mutational signatures associated with the microbiome, including the COSMIC reference signature SBS88. This signature is caused by exposure to Colibactin, a toxin produced by strains of Escherichia Coli which carry the pks pathogenicity island. The mutation burden of SBS88 was positively correlated with the age standardised rate (ASR) of CRC and was significantly more frequent in eoCRC. In addition, previous studies of the normal colon have shown that colibactin exposure likely occurs within the first decade of life. These results together suggest that the microbiome is contributing to the increase in eoCRC, and that it might be possible to assess the risk of eoCRC and/or control eoCRC incidence by monitoring the gut microbiome. This study aims to sequence both colorectal cancer and non-malignant colon to establish whether there is a causal relationship between colibactin exposure and eoCRC.","abstract":"The incidence of early onset colorectal cancer (eoCRC) has been increasing over the last few decades. Results from the whole genome sequencing of 982 colorectal cancers in the Mutographs study have identified several mutational signatures associated with the microbiome, including the COSMIC reference signature SBS88. This signature is caused by exposure to Colibactin, a toxin produced by strains of Escherichia Coli which carry the pks pathogenicity island. The mutation burden of SBS88 was positively correlated with the age standardised rate (ASR) of CRC and was significantly more frequent in eoCRC. In addition, previous studies of the normal colon have shown that colibactin exposure likely occurs within the first decade of life. These results together suggest that the microbiome is contributing to the increase in eoCRC, and that it might be possible to assess the risk of eoCRC and/or control eoCRC incidence by monitoring the gut microbiome. This study aims to sequence both colorectal cancer and non-malignant colon to establish whether there is a causal relationship between colibactin exposure and eoCRC.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007411","title":"Analysis of enhancer-promoter connectivity alterations","description":"The study uncovers epigenomic changes associated with dexamethasone response heterogeneity in myeloma cells, revealing rewired promoter-enhancer interactions and DNA loop stabilization","abstract":"The study uncovers epigenomic changes associated with dexamethasone response heterogeneity in myeloma cells, revealing rewired promoter-enhancer interactions and DNA loop stabilization","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-07T08:38:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007412","title":"Genomic evolution and transcriptional changes in the evolution of prostate cancer into neuroendocrine and ductal carcinoma types","description":"Prostate cancer is typically of acinar adenocarcinoma type but can occasionally present as neuro-endocrine and/or ductal type carcinoma. These are associated with clinically aggressive disease and the former often arises on a background of androgen deprivation therapy, although it can al-so arise de novo. Two prostate cancer cases were sequenced by exome capture from archival tis-sue. Case 1 was de novo small cell neuroendocrine carcinoma and ductal adenocarcinoma with 3 longitudinal samples over 5 years. Case 2 was a single time point after development of treatment related neuroendocrine prostate carcinoma. Case 1 showed whole genome doubling in all sam-ples and focal amplification of AR in all samples except the first time point. Phylogenetic analysis revealed a common ancestry for the ductal and small cell carcinoma. Case 2 showed 13q loss (involving RB1) in both adenocarcinoma and small cell carcinoma regions, and 3p gain, 4p loss, 17p loss (involving TP53) in the latter. By using highly curated samples, we demonstrate for the first time that small cell neuroendocrine and ductal prostatic carcinoma can have a common an-cestry and the process of evolution over time. We highlight whole genome doubling in a patient with prostate cancer relapse, reinforcing its poor prognostic nature.","abstract":"Prostate cancer is typically of acinar adenocarcinoma type but can occasionally present as neuro-endocrine and/or ductal type carcinoma. These are associated with clinically aggressive disease and the former often arises on a background of androgen deprivation therapy, although it can al-so arise de novo. Two prostate cancer cases were sequenced by exome capture from archival tis-sue. Case 1 was de novo small cell neuroendocrine carcinoma and ductal adenocarcinoma with 3 longitudinal samples over 5 years. Case 2 was a single time point after development of treatment related neuroendocrine prostate carcinoma. Case 1 showed whole genome doubling in all sam-ples and focal amplification of AR in all samples except the first time point. Phylogenetic analysis revealed a common ancestry for the ductal and small cell carcinoma. Case 2 showed 13q loss (involving RB1) in both adenocarcinoma and small cell carcinoma regions, and 3p gain, 4p loss, 17p loss (involving TP53) in the latter. By using highly curated samples, we demonstrate for the first time that small cell neuroendocrine and ductal prostatic carcinoma can have a common an-cestry and the process of evolution over time. We highlight whole genome doubling in a patient with prostate cancer relapse, reinforcing its poor prognostic nature.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-09T19:52:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007413","title":"Microbiome confounders and quantitative profiling challenge established microbial targets in colorectal cancer developmental stages","description":null,"abstract":"Despite significant progress, recognized microbiota confounders and advances in absolute microbiome quantification remain underused in cancer microbiome research. Here, we study the fecal microbiota of 589 patients at different stages of CRC development. Quantitative Microbiome Profiling based on 16S RNA amplicon-sequencing combined with rigorous confounder control, identified microbiota covariates.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-02-23T13:34:32.962702+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007414","title":"DERMATLAS__Fibroxanthoma_and_Pleomorphic_Dermal_Sarcoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Fibroxanthoma and Pleomorphic Dermal Sarcoma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Fibroxanthoma and Pleomorphic Dermal Sarcoma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007415","title":"Mutational_burden_in_oesophagus_following_chemotherapy_and_radiotherapy_treatment_WGS","description":"We wish to assess the changes in signature and mutational burden in patients who have undergone either chemotherapy or chemotherapy + radiotherapy.  Using duplex sequencing will assess the mutational landscape in oesophageal epithelia in patients who have undergone these treatment regimes.","abstract":"We wish to assess the changes in signature and mutational burden in patients who have undergone either chemotherapy or chemotherapy + radiotherapy.  Using duplex sequencing will assess the mutational landscape in oesophageal epithelia in patients who have undergone these treatment regimes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-12T15:50:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007416","title":"The_effects_of_chemotherapy_and_radiation_in_human_oesophageal_epithelium__low_input","description":"Human oesophagus is a patchwork of competing mutant clones. We wish to see how this patchwork is altered under the extreme selection pressures of chemotherapy and radiotherapy both individually and combined.  We will sequence 0.25mm diameter punch biopsies from patients who have undergone chemotherapy and radiotherapy to assess how the mutational landscape has changed.","abstract":"Human oesophagus is a patchwork of competing mutant clones. We wish to see how this patchwork is altered under the extreme selection pressures of chemotherapy and radiotherapy both individually and combined.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-12T15:54:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007417","title":"The_effects_of_chemotherapy_and_radiation_in_human_oesophageal_epithelium","description":"Human oesophagus is a patchwork of competing mutant clones. We wish to see how this patchwork is altered under the extreme selection pressures of chemotherapy and radiotherapy both individually and combined.  We will sequence 2mm2 contiguous pieces of oesophageal epithelium from patients who have undergone chemotherapy and radiotherapy to assess how the mutational landscape has changed.","abstract":"Human oesophagus is a patchwork of competing mutant clones. We wish to see how this patchwork is altered under the extreme selection pressures of chemotherapy and radiotherapy both individually and combined.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-12T16:00:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007418","title":"The_effects_of_chemotherapy_and_radiation_in_human_oesophageal_epithelium_NS_V1_5","description":"Validation of new V1.5 sequencing kit","abstract":"Validation of new V1.5 sequencing kit","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007419","title":"HCA_Immune_Adult_CIDP_RNA_Managed_Access","description":"Leveraging single-cell sequencing technologies to shed light on the immune aetiology of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)","abstract":"The project will involve performing single-cell sequencing on immune cells extracted from the blood and spinal fluid of individuals with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in order to understand the immune mechanism driving the disorder. Data generated from patients with CIDP will be compared and contrasted to thatgenerated from “controls” (mostly patient with benign intracranial hypertension who require repeated lumbar punctures). The project may also involve performing spatial transcriptomics (using the 10X visium platform) of a small number of nerve biopsies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-12T16:52:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007420","title":"ctDNA: A Promising Biomarker for Predicting Recurrence in BRAF-negative Melanoma Patients The Journal of Molecular Diagnostics","description":"For patients with BRAF wild-type stage III and IV melanoma, there is an urgent clinical need to identify prognostic biomarkers and biomarkers predictive of treatment response. Circulating tumour DNA (ctDNA) is emerging as a blood-based biomarker and has shown promising results for many cancers, including melanoma. Methods: The purpose of this study was to identify targetable, tumour-derived mutations in patient blood that may lead to treatment alternatives and improved outcomes for BRAF-negative melanoma patients. Using a CAPP-seq pan-cancer gene panel, ctDNA from 150 plasma samples (n=106 patients) were assessed, including serial blood collections for a subset of patients (n=16). Results: Circulating tumour DNA (ctDNA) variants were detected in 85% of the patients, all in targetable pathways such as VEGFR, EGFR, PI3K/AKT, Bcl2/mTOR, ALK/MET, CDK4/6. Stage IV patients with low ctDNA concentrations, &lt;10ng/ml, had significantly better disease-specific survival and progression free survival. Patients with both high concentration of ctDNA and any detectable ctDNA variants had the worst prognosis. Additionally, these results indicated that longitudinal changes in ctDNA correlated with treatment response and disease progression determined by radiology. Conclusion: This study confirms that ctDNA has potential to be used as a non-invasive liquid biopsy to identify recurrent disease and detect targetable variants in patients with late-stage melanoma.","abstract":"For patients with BRAF wild-type stage III and IV melanoma, there is an urgent clinical need to identify prognostic biomarkers and biomarkers predictive of treatment response. Circulating tumour DNA (ctDNA) is emerging as a blood-based biomarker and has shown promising results for many cancers, including melanoma. Methods: The purpose of this study was to identify targetable, tumour-derived mutations in patient blood that may lead to treatment alternatives and improved outcomes for BRAF-negative melanoma patients. Using a CAPP-seq pan-cancer gene panel, ctDNA from 150 plasma samples (n=106 patients) were assessed, including serial blood collections for a subset of patients (n=16). Results: Circulating tumour DNA (ctDNA) variants were detected in 85% of the patients, all in targetable pathways such as VEGFR, EGFR, PI3K/AKT, Bcl2/mTOR, ALK/MET, CDK4/6. Stage IV patients with low ctDNA concentrations, &lt;10ng/ml, had significantly better disease-specific survival and progression free survival. Patients with both high concentration of ctDNA and any detectable ctDNA variants had the worst prognosis. Additionally, these results indicated that longitudinal changes in ctDNA correlated with treatment response and disease progression determined by radiology. Conclusion: This study confirms that ctDNA has potential to be used as a non-invasive liquid biopsy to identify recurrent disease and detect targetable variants in patients with late-stage melanoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007421","title":"Prognostic markers of DNA methylation and NGS sequencing in progressive glioblastoma from the EORTC-26101 trial","description":"These dataset contains NGS data from 380 samples from the EORTC-26101 clinical trial for patients with progressive glioblastoma.","abstract":"These dataset contains NGS data from 380 samples from the EORTC-26101 clinical trial for patients with progressive glioblastoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-13T08:38:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007422","title":"RCC_microenvironment_WES","description":"This study aims to determine the driver landscape of the tumour microenvironment in RCC. The samples are minibulk samples for each major cell lineage. WES is used as the yields are too low for high-depth targetted nanoseq.","abstract":"WES of flow-sorted mini-bulks of the TME.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007423","title":"Identification of IQCH as a calmodulin-associated protein required for sperm motility in humans","description":null,"abstract":"We searched for causal genes / variants for a single asthenozoospermia patient by exome sequencing. We identified two homozygous deleterious variants in IQCH and MAP7D3. We showed the cumulative pathological impact of gene mutations and identifies IQCH as a key protein required for sperm motility and capacitation.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007424","title":"Childhood_Cancer_Paediatric_Behjati_SRF_Targeted_Nanoseq_TE_96389176_Managed_Access","description":"An exploratory study using targeted NanoSeq on a bait set of common paediatric cancer genes and cancer predisposition genes to assess mutations, mutational signatures, treatment effect, risk of relapse and to study the development of childhood cancer.","abstract":"An exploratory study using targeted NanoSeq on a bait set of common paediatric cancer genes and cancer predisposition genes to assess mutations, mutational signatures, treatment effect, risk of relapse and to study the development of childhood cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-13T12:36:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007425","title":"Childhood_Cancer_Foetal_Behjati_SRF_Targeted_Nanoseq_TE_96389176_Managed_Access_Foetal","description":"An exploratory study using targeted NanoSeq on a bait set of common paediatric cancer genes and cancer predisposition genes to assess mutations, mutational signatures, treatment effect, risk of relapse and to study the development of childhood cancer.","abstract":"An exploratory study using targeted NanoSeq on a bait set of common paediatric cancer genes and cancer predisposition genes to assess mutations, mutational signatures, treatment effect, risk of relapse and to study the development of childhood cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007426","title":"Translation of non-canonical open reading frames as a cancer cell survival mechanism in childhood medulloblastoma","description":"A hallmark of high-risk childhood medulloblastoma is the dysregulation of RNA translation. Currently, it is unknown whether medulloblastoma dysregulates the translation of putatively oncogenic non-canonical open reading frames. To address this question, we performed ribosome profiling of 32 medulloblastoma tissues and cell lines and observed widespread non-canonical ORF translation. We then developed a step-wise approach to employ multiple CRISPR-Cas9 screens to elucidate functional non-canonical ORFs implicated in medulloblastoma cell survival. We determined that multiple lncRNA-ORFs and upstream open reading frames (uORFs) exhibited selective functionality independent of the main coding sequence. One of these, ASNSD1-uORF or ASDURF, was upregulated, associated with the MYC family oncogenes, and was required for medulloblastoma cell survival through engagement with the prefoldin-like chaperone complex. Our findings underscore the fundamental importance of non-canonical ORF translation in medulloblastoma and provide a rationale to include these ORFs in future cancer genomics studies seeking to define new cancer targets.","abstract":"A hallmark of high-risk childhood medulloblastoma is the dysregulation of RNA translation. Currently, it is unknown whether medulloblastoma dysregulates the translation of putatively oncogenic non-canonical open reading frames. To address this question, we performed ribosome profiling of 32 medulloblastoma tissues and cell lines and observed widespread non-canonical ORF translation. We then developed a step-wise approach to employ multiple CRISPR-Cas9 screens to elucidate functional non-canonical ORFs implicated in medulloblastoma cell survival. We determined that multiple lncRNA-ORFs and upstream open reading frames (uORFs) exhibited selective functionality independent of the main coding sequence. One of these, ASNSD1-uORF or ASDURF, was upregulated, associated with the MYC family oncogenes, and was required for medulloblastoma cell survival through engagement with the prefoldin-like chaperone complex. Our findings underscore the fundamental importance of non-canonical ORF translation in medulloblastoma and provide a rationale to include these ORFs in future cancer genomics studies seeking to define new cancer targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-13T13:47:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007427","title":"Single-cell proteogenomics of MDS upon AZA","description":"To study the evolution of the clonal molecular and cellular architecture of MDS upon the treatment with AZA, we performed scDNA-seq of an amplicon panel of 53 genes recurrently mutated in myeloid malignancies, as well as typically lost or gain DNA regions, and scProt-seq of 42 cell-surface proteins to provide a simultaneous landscape of the genetic setting and immunophenotype using the Tapestri platform (MissionBio). We sequenced thousands of cells from 14 MDS patients, where paired bone marrow samples were obtained at the timepoint of diagnosis and after AZA treatment.","abstract":"To study the evolution of the clonal molecular and cellular architecture of MDS upon the treatment with AZA, we performed scDNA-seq of an amplicon panel of 53 genes recurrently mutated in myeloid malignancies, as well as typically lost or gain DNA regions, and scProt-seq of 42 cell-surface proteins to provide a simultaneous landscape of the genetic setting and immunophenotype using the Tapestri platform (MissionBio). We sequenced thousands of cells from 14 MDS patients, where paired bone marrow samples were obtained at the timepoint of diagnosis and after AZA treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-13T15:23:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007428","title":"Genomic evolution and transcriptional changes in the evolution of prostate cancer into neuroendocrine and ductal carcinoma types (RNAseq)","description":"Prostate cancer is typically of acinar adenocarcinoma type but can occasionally present as neuro-endocrine and/or ductal type carcinoma. These are associated with clinically aggressive disease and the former often arises on a background of androgen deprivation therapy, although it can al-so arise de novo. Two prostate cancer cases were sequenced by exome capture from archival tis-sue. Case 1 was de novo small cell neuroendocrine carcinoma and ductal adenocarcinoma with 3 longitudinal samples over 5 years. Case 2 was a single time point after development of treatment related neuroendocrine prostate carcinoma. Case 1 showed whole genome doubling in all sam-ples and focal amplification of AR in all samples except the first time point. Phylogenetic analysis revealed a common ancestry for the ductal and small cell carcinoma. Case 2 showed 13q loss (involving RB1) in both adenocarcinoma and small cell carcinoma regions, and 3p gain, 4p loss, 17p loss (involving TP53) in the latter. By using highly curated samples, we demonstrate for the first time that small cell neuroendocrine and ductal prostatic carcinoma can have a common an-cestry and the process of evolution over time. We highlight whole genome doubling in a patient with prostate cancer relapse, reinforcing its poor prognostic nature.","abstract":"Prostate cancer is typically of acinar adenocarcinoma type but can occasionally present as neuro-endocrine and/or ductal type carcinoma. These are associated with clinically aggressive disease and the former often arises on a background of androgen deprivation therapy, although it can al-so arise de novo. Two prostate cancer cases were sequenced by exome capture from archival tis-sue. Case 1 was de novo small cell neuroendocrine carcinoma and ductal adenocarcinoma with 3 longitudinal samples over 5 years. Case 2 was a single time point after development of treatment related neuroendocrine prostate carcinoma. Case 1 showed whole genome doubling in all sam-ples and focal amplification of AR in all samples except the first time point. Phylogenetic analysis revealed a common ancestry for the ductal and small cell carcinoma. Case 2 showed 13q loss (involving RB1) in both adenocarcinoma and small cell carcinoma regions, and 3p gain, 4p loss, 17p loss (involving TP53) in the latter. By using highly curated samples, we demonstrate for the first time that small cell neuroendocrine and ductal prostatic carcinoma can have a common an-cestry and the process of evolution over time. We highlight whole genome doubling in a patient with prostate cancer relapse, reinforcing its poor prognostic nature.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-13T16:50:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007429","title":"Formalin_fixed_tissue_sequencing__RE_NanoSeq_","description":"This study aims to examine the feasibility, efficacy, and accuracy of restriction enzyme NanoSeq in tissues fixed in formalin. This has thought to be limited due to the DNA crosslinks introduced in the fixation process. By using nanorate error-corrected duplex sequencing, we hope to establish the mutation burden and signatures within formalin-fixed tissues and compare with non-formalin fixed tissues, to assess the excess error rate, if any. Initially this is limited to pancreas and AMSBIO samples as we have the largest cohorts providing the necessary age ranges. Following this pilot project, we will likely look to expand the tissues sequenced to further confirm the observations.","abstract":"Investigating the mutation burden and mutational signatures in formalin-fixed tissues.\nInvestigating the feasibility, efficacy, and accuracy of using NanoSeq in formalin-fixed tissues.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007430","title":"Patient-derived organoids identify tailored therapeutic options and determinants of plasticity in sarcomatoid urothelial bladder cancer","description":null,"abstract":"Sarcomatoid Urothelial Bladder Cancer (SARC) is a rare and aggressive histological subtype of bladder cancer for which therapeutic options are limited and experimental models are lacking. In this study, we established and characterized the first long-term 3D organoid-like model derived from a SARC patient (SarBC-01). High-throughput drug screening identified drug candidates active against SARC cells exclusively, or UroCa cells exclusively, or both. Among those, a subset of targeted drugs was specifically effective in SARC cells, such as agents targeting the Glucocorticoid Receptor (GR) pathway. In two independent patient cohorts, GR was found to be significantly more expressed, at mRNA and protein level, in SARC as compared to UroCa tumor samples. Further, glucocorticoid treatment impaired the mesenchymal morphology, abrogated the invasive ability of SARC cells, and led to transcriptomic changes associated with reversion of epithelial-to-mesenchymal transition, at single-cell level. Altogether, our study highlights the power of organoids for precision oncology and for providing key insights into factors driving rare tumor entities.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-13T21:45:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007431","title":"Genomic characterization of hepatocellular carcinoma in Hispanic patients","description":"The genomic DNA was extracted from paired tumor and adjacent non-tumor samples of 27 Hispanic HCC patients. The TruSeq Rapid Exome Library Prep kit (Illumina, CA) was used to capture the coding regions of the human genome. The 100 bp paired-end sequencing of every 6-plex whole exome library pool was performed on an Illumina HiSeq 3000 system according to the manufacturer’s recommended protocol to achieve an average coverage of ~100X. The paired-end reads were aligned to the human reference genome (hg19) with decoy sequences (as used in the 1000 Genomes Project) using BWA software. The duplicate reads were marked and removed using Picard and SAMtools, respectively. Local realignment around insertions/deletions (indels) and base quality recalibration were performed using GATK.","abstract":"The genomic DNA was extracted from paired tumor and adjacent non-tumor samples of 27 Hispanic HCC patients. The TruSeq Rapid Exome Library Prep kit (Illumina, CA) was used to capture the coding regions of the human genome. The 100 bp paired-end sequencing of every 6-plex whole exome library pool was performed on an Illumina HiSeq 3000 system according to the manufacturer’s recommended protocol to achieve an average coverage of ~100X. The paired-end reads were aligned to the human reference genome (hg19) with decoy sequences (as used in the 1000 Genomes Project) using BWA software. The duplicate reads were marked and removed using Picard and SAMtools, respectively. Local realignment around insertions/deletions (indels) and base quality recalibration were performed using GATK.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-13T23:56:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007432","title":"Regenerative effects of MSC treatment on busulfan-induced small intestine damaged organoids.","description":"Allogenic hematopoietic stem cell transplantation (HSCT) is a curative treatment for leukemia and a range of non-malignant disorders. The success of the therapy is hampered by occurrence of acute graft-versus-host disease (aGvHD); an inflammatory response damaging recipient organs, with gut, liver, and skin being the most susceptible. Intestinal GvHD injury is often a life-threatening complication in patients unresponsive to steroid treatment. Second-line available therapies are immunosuppressants or mesenchymal stromal/stem cell (MSC) infusions. Data from our institution and others demonstrate rescue of approximately 40-50% of patients suffering from aGvHD with mesenchymal stromal/stem cells (MSCs) and minor side effects. Although promising, the better understanding of MSC mode of action and patient response to MSC-based therapy is essential to improve this lifesaving treatment. Here, we developed a novel 3D co-culture model of human small intestinal organoids and MSCs, which allows to study the regenerative effects of MSCs on intestinal epithelium in a more physiologically relevant setting than existing in vitro systems. Using this model we mimicked chemotherapy-mediated damage of the intestinal epithelium. The treatment with busulfan, the chemotherapeutic commonly used as conditioning regiment before the HSCT, affected pathways regulating EMT, proliferation, and apoptosis in small intestinal organoids, as shown by transcriptomic and proteomic analysis. The co-culture of busulfan treated intestinal organoids with MSCs reversed the effects of busulfan on the transcriptome and proteome of intestinal epithelium, which we also confirmed by functional evaluation of proliferation and apoptosis. Collectively, we demonstrate that our novel in vitro co-culture system is a new valuable tool to facilitate the investigation of the molecular mechanisms behind the therapeutic effects of MSCs on damaged intestinal epithelium.","abstract":"Allogenic hematopoietic stem cell transplantation (HSCT) is a curative treatment for leukemia and a range of non-malignant disorders. The success of the therapy is hampered by occurrence of acute graft-versus-host disease (aGvHD); an inflammatory response damaging recipient organs, with gut, liver, and skin being the most susceptible. Intestinal GvHD injury is often a life-threatening complication in patients unresponsive to steroid treatment. Second-line available therapies are immunosuppressants or mesenchymal stromal/stem cell (MSC) infusions. Data from our institution and others demonstrate rescue of approximately 40-50% of patients suffering from aGvHD with mesenchymal stromal/stem cells (MSCs) and minor side effects. Although promising, the better understanding of MSC mode of action and patient response to MSC-based therapy is essential to improve this lifesaving treatment. Here, we developed a novel 3D co-culture model of human small intestinal organoids and MSCs, which allows to study the regenerative effects of MSCs on intestinal epithelium in a more physiologically relevant setting than existing in vitro systems. Using this model we mimicked chemotherapy-mediated damage of the intestinal epithelium. The treatment with busulfan, the chemotherapeutic commonly used as conditioning regiment before the HSCT, affected pathways regulating EMT, proliferation, and apoptosis in small intestinal organoids, as shown by transcriptomic and proteomic analysis. The co-culture of busulfan treated intestinal organoids with MSCs reversed the effects of busulfan on the transcriptome and proteome of intestinal epithelium, which we also confirmed by functional evaluation of proliferation and apoptosis. Collectively, we demonstrate that our novel in vitro co-culture system is a new valuable tool to facilitate the investigation of the molecular mechanisms behind the therapeutic effects of MSCs on damaged intestinal epithelium.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-14T11:16:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007433","title":"The Gut Microbiome of lung transplant recipients and healthy controls","description":null,"abstract":"TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains 282 samples collected both cross-sectionally and longitudinally from lung transplant recipients as well as 68 samples from healthy controls. Metagenomics library preparation and sequencing were done at MGI as part of the Million Microbiome of Humans Project (MMHP).","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007434","title":"Clonal_dynamics_and_mutation_burden_in_male_germline___Targeted_NanoSeq__CamIVF_","description":"This work aims to study clonal dynamics of pathogenic mutations in male germline using targeted NanoSeq in sperm samples provided by IVF clinic patients and a custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Little is known about mutagenesis within the hierarchy of spermatogenesis or factors that influence rates of mutation in the testes/sperm. It is likely that mutations in spermatogonia stem cells that confer weaker selective advantage and generate smaller clonal expansions in the testes, become enrich in sperms and transmit to the next generations. However, due to the low sensitivity of standard genomic approaches, subclonal mutations that may only be present in small contiguous areas within testes have been poorly investigated.  Additionally the links of these mutations to male fertility are poorly understood.\n\nThis proposal aims to measure the mutational burden of pathogenic variants in sperm and to identify the processes that underlie their acquisition and their links to fertility.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007435","title":"Targeted_NanoSeq__Breast_health_and_disease_","description":"We will apply targeted nanoseq to neoplastic and normal breast tissues from individuals with a cancer and a known or suspected hypermutator phenotype. The very low error rate of nanoseq is hoped to provide a more accurate view of the cell to cell diversity and operation of selection in these cases.","abstract":"Breast cancers with an unusually high mutation burden detected using conventional whole genome sequencing (WGS) approaches are described as having a hypermutator phenotype. The high rate of diversity generation in hypermutator cancers can provide an opportunity to explore the action of positive and negative selection operating in different scenarios. Combining regional sampling and WGS can expose some of the evolutionary patterns that result in moderate-large clonal expansions. Yet, we know little about the rate or nature of selection operating to generate cell to cell diversity and the overall driver burden. Here we take advantage of the extremely low error rate of targeted nanoseq to ascertain the burden of mutations within known cancer genes in breast tissues from individuals with hypermutator tumours. For tumours, by comparing to WGS analyses where we have pre-existing knowledge of the gross phylogenetic tree structure we will ascertain whether we can reliably distinguish between mutations drawn from different clonal population sizes such as: clonal, large subclonal and minor subclonal with the latter falling below the detection threshold using conventional genomic sequencing. We will examine selection processes operating within the different population sizes, especially in the terminal, rarer clones that will be invisible to standard WGS. In normal tissues we will explore the mutation burden, mutational processes and selection patterns operating.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007436","title":"Finding structural variation and functional consequences from primary acute myeloid leukemia cells with complex karyotype (CK-AML) at the single-cell level","description":null,"abstract":"In this study, we aimed to extend our understanding of the intra-tumor heterogeneity evolution in CK-AML and exemplify the translational relevance of single-cell clonal evolution analyses. To achieve this, we leveraged two single-cell multi-omics frameworks, scNOVA and CITE-seq, to link genotype, epigenome and phenotype of four primary CK-AML patients, and coupled this with functional xenotransplantation assays.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-17T08:48:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007437","title":"HCA_Gut_Paediatric_Hirschsprung_s_disease_Teichmann_WGS_Managed_Access","description":"This study involves atlasing the development of the postnatal gut nervous system in order to elucidate the pathogenic mechanisms of Hirschsprung disease.","abstract":"Hirschsprung’s disease (HD) is congenital condition where the enteric neurons and glia are absent in parts of the bowel. HD is a genetic disease in which enteric ganglia development is implicated. Currently, the interplay between causal HD genes and development of the enteric neuron system remains obscure. Here, we will combine whole genome sequencing, single nuclei multiomic analysis (10x multiome, scRNA+scATAC) and spatial transcriptomics analysis on frozen HD and healthy colonic tissue to uncover the mechanisms of HD pathogenesis","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-17T09:28:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007438","title":"Intra-prostatic tumour evolution, steps in metastatic spread and histogenomic associations revealed by integration of multi-region whole genome sequencing with histopathological features","description":"We performed whole genome sequencing on 42 prostate cancer samples from the prostate, seminal vesicles and regional lymph nodes of five treatment-naive patients with locally advanced disease who underwent radical prostatectomy. Using cancer cell fractions computed from single nucleotide variants and copy number alterations, we reconstructed the tumour phylogenies, which in turn allowed us to infer key molecular steps in the progression of prostate cancer in these individuals. We mapped the clonal composition of cancer sampled across the prostate in each individual and inferred the routes of spread of cancer cells within the prostate and to seminal vesicles and lymph nodes.","abstract":"We performed whole genome sequencing on 42 prostate cancer samples from the prostate, seminal vesicles and regional lymph nodes of five treatment-naive patients with locally advanced disease who underwent radical prostatectomy. Using cancer cell fractions computed from single nucleotide variants and copy number alterations, we reconstructed the tumour phylogenies, which in turn allowed us to infer key molecular steps in the progression of prostate cancer in these individuals. We mapped the clonal composition of cancer sampled across the prostate in each individual and inferred the routes of spread of cancer cells within the prostate and to seminal vesicles and lymph nodes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-17T11:24:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007439","title":"DERMATLAS__Myxoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Myxomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Myxomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007440","title":"DERMATLAS__Myxoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Myxoma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Myxoma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007441","title":"DERMATLAS__Extramammary_Paget_Disease_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Extramammary Paget Disease.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Extramammary Paget Disease.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007442","title":"DERMATLAS__Extramammary_Paget_Disease_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Extramammary Paget Disease.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Extramammary Paget Disease.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007443","title":"DERMATLAS__Myofibroma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Myofibroma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Myofibroma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007444","title":"DERMATLAS__Myofibroma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Myofibroma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Myofibroma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007445","title":"CUPiD, a cfDNA methylation-based tissue-of-origin classifier for Cancers of Unknown Primary","description":null,"abstract":"Cancers of Unknown Primary (CUP) remains a diagnostic and therapeutic challenge due to biological heterogeneity and poor responses to standard chemotherapy. Predicting tissue-of-origin (TOO)  molecularly could help refine this diagnosis, with tissue acquisition barriers mitigated via liquid biopsies. However, TOO liquid biopsies have yet to be explored in CUP cohorts. Using publicly available DNA methylation data, we developed a machine learning classifier termed CUPiD with accurate TOO predictions across 29 tumour classes. We tested CUPiD on 143 cfDNA samples from patients with 13 cancer types alongside 27 non-cancer controls, with overall sensitivity of 87.1% and specificity of 97.9%. CUPiD predictions for a further 41 patients with CUP were made for 78.0% of cases, of which 71.9% were clinically consistent with a subsequent or suspected primary tumour diagnosis. Combining CUPiD with cfDNA mutation data demonstrated potential diagnosis re-classification and/or treatment change in this hard-to-treat cancer group.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-17T15:16:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007446","title":"TallFlow: Lineage tracing of immunophenotypic sub populations in T-cell Acute lymphoblastic leukemia by (sc-)WGS","description":null,"abstract":"To examine the genetic clonality of immunophenotypic subpopulations in T-cell Acute lymphoblastic leukaemia. Using single-cell WGS and bulk-sorted populations we aim to perform retrospective lineage tracing of these phenotypic subclones to study plasticity.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-06-03T16:02:18.468321+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007447","title":"CRISPR_Cas9_screens_in_organoids_treated_with_MEKi","description":"In this study, the researchers will perform CRISPR-Cas9 screens in organoids derived from patient-derived xenografts, focusing on both KRAS-dependent and KRAS-independent organoids. The purpose of these screens is to identify genes whose knockout or modification affects sensitivity to MEK inhibitors, which are drugs targeting the MEK signaling pathway. By transducing a genetic library into the organoids and treating them with MEK inhibitors, the study aims to observe how the knockout or modification of certain genes influences the organoids' response to MEK inhibition. The identification of specific genes involved in MEK inhibitor sensitivity, particularly in the context of KRAS-dependence, can provide valuable insights into potential therapeutic targets and improve the effectiveness of MEK inhibitor treatments.","abstract":"In this study, organoids derived from patient-derived xenografts will undergo CRISPR-Cas9 screens to identify genes influencing sensitivity to MEK inhibitors. Specifically, KRAS-dependent or KRAS-independent organoids will be selected for analysis in order to assess the impact of gene modifications on MEK inhibition response.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007448","title":"Molecular analysis of surgical margin tissue to guide resection extent in oropharyngeal squamous cell carcinoma (OPSCC)","description":null,"abstract":"How does the methylome of a histologically negative surgical margin compare to the primary tumor and contralateral healthy mucosa?\nIn this study of 71 primary tumors (TU), 38 clear resection margin (RM), and 16 contralateral healthy mucosae (HM) samples, methylation analysis revealed that despite the resemblance between HM and RM, from a methylation standpoint, RM exhibits similarities to TU, most significantly in recurrent cases.\nOur analysis suggests that features exhibiting similar methylation patterns between TU and RM could characterize margin tissue at risk of disease recurrence.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007449","title":"Methylome study on human spermatogenic cells","description":null,"abstract":"DNA methylation is an important regulator of the chromatin structure and is necessary for gene expression stability and maintenance of cell identitiy. However, to which extent DNA methylation changes during the key differentiation steps of human spermatogenesis remains largely unkown. Here, we generated genome wide methylomes (Enzymatic Methyl-sequencing) of human undifferentiated spermatogonia (Undiff), differentiating spermatogonia (Diff), tetraploid spermatocytes (4C) and haploid spermatids (1C) obtained from testicular tissues of three patients with qualitatively and quantitatively normal spermatogenesis (control, CTR). We also generated Undiff, Diff and 4C methylomes from two patients with impaired spermatogenesis (cryptozoospermic, CZ). Our study is the first to report about DNA methylation changes during human spermatogenesis.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-19T08:50:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007450","title":"RSV infection of primary bronchial epithelial cells in asthma","description":"Primary bronchial epithelial cells derived from healthy donors and asthma patients were differentiated in Air-Liquid-Interface condition and infected with the respiratory syncytial virus. Single-cell RNA sequencing analysis of these cultures was used to study the transcriptomic response of the cells to RSV.","abstract":"Primary bronchial epithelial cells derived from healthy donors and asthma patients were differentiated in Air-Liquid-Interface condition and infected with the respiratory syncytial virus. Single-cell RNA sequencing analysis of these cultures was used to study the transcriptomic response of the cells to RSV.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-20T08:51:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007451","title":"Machine Learning Signal Enrichment for Ultrasensitive Plasma Tumor Burden Monitoring","description":"In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole genome sequencing (WGS). We now introduce MRD-EDGE, a composite machine learning-guided WGS ctDNA single nucleotide variant (SNV) and copy number variant (CNV) detection platform designed to increase signal enrichment. MRD-EDGESNV uses deep learning and a ctDNA-specific feature space to increase SNV signal-to-noise enrichment in WGS by 300X compared to previous WGS error suppression. MRD-EDGECNV also reduces the degree of aneuploidy needed for ultrasensitive CNV detection through WGS from 1 Gb to 200 Mb, thereby expanding its applicability to a wider range of solid tumors. We harness the improved performance to identify MRD following surgery in multiple cancer types, track changes in tumor burden in response to neoadjuvant immunotherapy in non-small cell lung cancer (NSCLC) and demonstrate ctDNA shedding in precancerous colorectal adenomas. Finally, the radical signal-to-noise enrichment in MRD-EDGESNV enables de novo mutation calling in melanoma and small cell lung cancer (SCLC) without matched tumor, yielding clinically informative TF monitoring for patients on immune checkpoint inhibition (ICI).","abstract":"In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole genome sequencing (WGS). We now introduce MRD-EDGE, a composite machine learning-guided WGS ctDNA single nucleotide variant (SNV) and copy number variant (CNV) detection platform designed to increase signal enrichment. MRD-EDGESNV uses deep learning and a ctDNA-specific feature space to increase SNV signal-to-noise enrichment in WGS by 300X compared to previous WGS error suppression. MRD-EDGECNV also reduces the degree of aneuploidy needed for ultrasensitive CNV detection through WGS from 1 Gb to 200 Mb, thereby expanding its applicability to a wider range of solid tumors. We harness the improved performance to identify MRD following surgery in multiple cancer types, track changes in tumor burden in response to neoadjuvant immunotherapy in non-small cell lung cancer (NSCLC) and demonstrate ctDNA shedding in precancerous colorectal adenomas. Finally, the radical signal-to-noise enrichment in MRD-EDGESNV enables de novo mutation calling in melanoma and small cell lung cancer (SCLC) without matched tumor, yielding clinically informative TF monitoring for patients on immune checkpoint inhibition (ICI).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-20T17:10:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007452","title":"Transcriptional network analysis of peripheral blood leukocyte subsets in Multiple Sclerosis","description":null,"abstract":"Multiple Sclerosis (MS) is a disabling autoinflammatory disease of the central nervous system (CNS), associated with both environmental and genetic risk factors. Although &gt;230 risk-SNPs have been identified as associated with MS to date, the mechanisms by which they contribute to MS risk, remain elusive.  Our approach to address this issue is based on the hypothesis that complex genetic phenotypes are driven by coordinated expression of transcriptional regulatory networks. We, therefore, constructed a gene co-expression network from microarray expression analyses of five purified peripheral blood leukocyte (PBL) subsets of 76 relapsing/remitting (RR) MS patients and 104 healthy controls (HC). These analyses identified a major module of networked genes that play key roles in cell-mediated cytotoxicity and were downregulated in monocytes of MS patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007453","title":"Whole_Genome_Sequencing_OMELib__Cord_blood_","description":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the Cambridge Biobank.","abstract":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the Cambridge Biobank.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-21T09:23:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007454","title":"RNA_Seq_OMELib__Cord_blood_","description":"The transcriptional landscape of haematopoietic cells will be characterized by RNA Seq following amplification of RNA/cDNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the Cambridge Biobank.","abstract":"The transcriptional landscape of haematopoietic cells will be characterized by RNA Seq following amplification of RNA/cDNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the Cambridge Biobank.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-21T09:28:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007455","title":"HSC_population_dynamics_in_perturbation___73F_samples","description":"The aim of this project is to characterise how the systemic environment shapes the clonal landscape in adult humans and how perturbations affect this landscape. We are collecting longitudinal samples from patients before and after chemotherapy, in order to perform whole genome sequencing on their HSCs and, using patterns of shared and unique mutations, construct a phylogenetic tree of each patient’s HSCs. This will allow us to interrogate how clonal composition changes in response to chemotherapy, shedding insight into the fitness of mutations with respect to age and treatment. \nThe questions I want to answer: \n1. Are mutations that gave some HSCs an advantage, which resulted in their clonal expansion, still advantageous in the new environment? Does chemotherapy favour some mutations over others? \n2. How do chemotherapies of different intensities affect the clonal landscape of HSCs? \n3. How does ageing affect the ability of the hematopoietic system to recover after chemotherapy? Are any clinical variables associated with improved recovery? \n4. Does the population of HSCs remain unchanged?\n5. How do different chemotherapies contribute to mutagenesis of HSCs?","abstract":"Background \nWith age, somatic mutations accumulate in normal dividing cells, including hematopoietic stem cells (HSCs). It appears that some mutations provide HSCs with a fitness advantage, allowing their mutant daughter blood cells to disproportionately expand (Jaiswal &amp; Ebert, 2019). The phenomenon is termed clonal hematopoiesis (CH) and it is associated with ageing as well as hematologic malignancies, cardiovascular disease and all-cause mortality (Genovese et al., 2014; Jaiswal &amp; Ebert, 2019). Preliminary evidence suggests that after a perturbation such as cancer therapy, the composition of clones, which dominate the hematopoietic system, changes (Bolton, 2020). However, the studies carried out until now have analysed CH at the population level, but little is known about the process at an individual level. Moreover, no study until now has addressed how perturbations of the systemic environment affect the clonal composition of blood at the single-cell level. \nCohort Description \nWe will take peripheral blood samples from 1 normal individual and 14 patients undergoing chemotherapy for the treatment of lymphoma with confirmed absence of bone marrow involvement. The chemotherapy-treated cohort will consist of 4 younger adults (aged under 55 years) and 8 older adults (aged over 70 years) who will all be receiving R- CHOP for treating diffuse large B-cell lymphoma as well as 2 younger adults who are receiving a more intensive chemotherapy regimen such as BEACOPP or ABVD for the treatment of Hodgkin’s lymphoma. The described design will allow us to compare the response of the hematopoietic system at different ages to chemotherapy of different intensities, as well as provide a control to ensure longitudinal changes are not observed in normal, healthy individuals.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007456","title":"HSC_population_dynamics_in_perturbation___75F_samples__normal_control_","description":"The aim of this project is to characterise how the systemic environment shapes the clonal landscape in adult humans and how perturbations affect this landscape. We are collecting longitudinal samples from patients before and after chemotherapy, in order to perform whole genome sequencing on their HSCs and, using patterns of shared and unique mutations, construct a phylogenetic tree of each patient’s HSCs. This will allow us to interrogate how clonal composition changes in response to chemotherapy, shedding insight into the fitness of mutations with respect to age and treatment. \nThe questions I want to answer: \n1. Are mutations that gave some HSCs an advantage, which resulted in their clonal expansion, still advantageous in the new environment? Does chemotherapy favour some mutations over others? \n2. How do chemotherapies of different intensities affect the clonal landscape of HSCs? \n3. How does ageing affect the ability of the hematopoietic system to recover after chemotherapy? Are any clinical variables associated with improved recovery? \n4. Does the population of HSCs remain unchanged?\n5. How do different chemotherapies contribute to mutagenesis of HSCs?","abstract":"Background \nWith age, somatic mutations accumulate in normal dividing cells, including hematopoietic stem cells (HSCs). It appears that some mutations provide HSCs with a fitness advantage, allowing their mutant daughter blood cells to disproportionately expand (Jaiswal &amp; Ebert, 2019). The phenomenon is termed clonal hematopoiesis (CH) and it is associated with ageing as well as hematologic malignancies, cardiovascular disease and all-cause mortality (Genovese et al., 2014; Jaiswal &amp; Ebert, 2019). Preliminary evidence suggests that after a perturbation such as cancer therapy, the composition of clones, which dominate the hematopoietic system, changes (Bolton, 2020). However, the studies carried out until now have analysed CH at the population level, but little is known about the process at an individual level. Moreover, no study until now has addressed how perturbations of the systemic environment affect the clonal composition of blood at the single-cell level. \nCohort Description \nWe will take peripheral blood samples from 1 normal individual and 14 patients undergoing chemotherapy for the treatment of lymphoma with confirmed absence of bone marrow involvement. The chemotherapy-treated cohort will consist of 4 younger adults (aged under 55 years) and 8 older adults (aged over 70 years) who will all be receiving R- CHOP for treating diffuse large B-cell lymphoma as well as 2 younger adults who are receiving a more intensive chemotherapy regimen such as BEACOPP or ABVD for the treatment of Hodgkin’s lymphoma. The described design will allow us to compare the response of the hematopoietic system at different ages to chemotherapy of different intensities, as well as provide a control to ensure longitudinal changes are not observed in normal, healthy individuals.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007457","title":"Spatial transcriptomics of triple negative breast cancers","description":null,"abstract":"Intratumoral heterogeneity (ITH) is one of the leading drivers of therapeutic resistance and is associated with poor survival (Jamal-Hanjani et al, Clin Can Res 2015; doi:10.1200/JCO.2011.39.5624, doi:10.1093/jnci/djr545, doi:10.1038/nm.3886, doi:10.1093/annonc/mdy024). While triple negative breast cancer (TNBC) is known to be highly heterogeneous at the genomic and transcriptomic levels, spatial information on the tumour  organization and cell composition is lacking. Here, we investigated TNBC tumour architecture including its microenvironment using spatial transcriptomics on a series of 94 TNBC samples. Following a pure histomorphological characterization of the samples, spatial expression deconvolution of the histomorphological compartments was performed for an in-depth description of the tumour and stroma organization and composition of each TNBC molecular subtype. Furthermore, a detailed molecular characterization of tertiary lymphoid structures (TLS) led to the identification of a gene signatures shown to be strongly associated to disease outcome and response to immunotherapy in several tumour types beyond TNBC. A stepwise clustering analysis identified nine distinct TNBC ecotypes, further validated in external datasets. Several ecotypes were associated with disease outcome and characterized by potentially actionable features. This is the largest TNBC series providing a comprehensive insight into the complexity of TNBC ecosystem with potential clinical relevance, opening avenues for the tailoring of treatments including immunotherapy.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007458","title":"Whole Genome sequencing of Angolan and Mozambican individuals","description":"To support the continued discovery and cataloguing of genomic variation in human populations and to further our understanding of the Bantu Expansion, we sequenced the genomes of 291 individuals from Cabinda, a northern exclave of Angola, and 49 individuals from Maputo, the capital of Mozambique. Utilising the power and flexibility of these whole-genome sequencing datasets, we discover rare variation, fine-scale population structure, and perform analyses using haplotype-based inference tools and our own model-based simulation framework to reconstruct complex dispersals of Bantu speak-ing populations across sub-Saharan Africa.","abstract":"To support the continued discovery and cataloguing of genomic variation in human populations and to further our understanding of the Bantu Expansion, we sequenced the genomes of 291 individuals from Cabinda, a northern exclave of Angola, and 49 individuals from Maputo, the capital of Mozambique. Utilising the power and flexibility of these whole-genome sequencing datasets, we discover rare variation, fine-scale population structure, and perform analyses using haplotype-based inference tools and our own model-based simulation framework to reconstruct complex dispersals of Bantu speak-ing populations across sub-Saharan Africa.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-24T15:17:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007459","title":"Elucidating the molecular landscape of KRAS/BRAF mutant colorectal cancers","description":null,"abstract":"Colorectal Cancer (CRC) is a highly heterogeneous group of diseases, with distinctive genetic and epigenetic alterations. CRC tumors bearing KRAS or BRAF mutations still remain resistant to new therapies. Thus, this augments the necessity to reveal new therapeutic targets in mutKRAS/BRAF, which may account for up to 50% of the total CRC patients. To this end, we investigated primary untreated CRC tumors (WES &amp; RNA-Seq) from 28 Greek patients for their systematic molecular characterization and stratification into diverse groups based on their microsatellite instability (MSI) status and KRAS/BRAF genetic variations, in order to unravel novel targets and putative personalized treatment interventions.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007460","title":"Knoll et al Identification of drug candidates targeting monocyte reprogramming in people living with HIV","description":"Introduction\r\nPeople living with HIV (PLHIV) are characterized by functional reprogramming of innate immune cells even after long-term antiretroviral therapy (ART). In order to assess technical feasibility of omics technologies for application to larger cohorts, we compared multiple omics layers.\r\nMethods\r\nBulk and single-cell transcriptomics, flow cytometry, proteomics, chromatin landscape analysis by ATAC-seq as well as ex vivo drug stimulation was performed in a small number of blood samples derived from PLHIV and healthy controls from the 200-HIV cohort study.\r\nResults\r\nSingle-cell RNA-seq analysis revealed that most immune cells in peripheral blood of PLHIV are altered in their transcriptomes and that a specific functional monocyte state previously described in acute HIV infection is still existing in PLHIV while other monocyte cell states are only occurring acute infection. Moreover, a reverse transcriptome approach on a rather small number of PLHIV was sufficient to identify drug candidates for reversing the transcriptional phenotype of monocytes in PLHIV.\r\nDiscussion\r\nThese scientific findings and technological advancements for clinical application of single-cell transcriptomics form the basis for the larger 2000-HIV multicenter cohort study on PLHIV, for which a combination of bulk and single-cell transcriptomics will be included as the leading technology to determine disease endotypes in PLHIV and to predict disease trajectories and outcomes.\r\n","abstract":"Following the demonstration of its life-saving effect in clinical trials, dexamethasone quickly became standard-of-care in the treatment of severe COVID-19. Beneficial effects were reported for patients requiring supplemental oxygen or invasive mechanical ventilation. Yet, a substantial proportion of patients still progressed to a critical condition or succumbed to the disease, despite timely initiation of glucocorticoid treatment. No molecular or cellular correlate of this beneficial treatment response has been defined. Here, we identify distinct cellular and molecular changes in circulating immune cells in patients with COVID-19 elicited in response to dexamethasone treatment. The most profound transcriptional changes in response to dexamethasone treatment were noted in monocytes and in B cells. In monocytes, we observed a reversal of hallmark signatures previously associated with COVID-19 severity, and the induction of a specific monocyte substate enriched in glucocorticoid response gene expression which we here refer to as dexamethasone response cluster. Molecular responses to dexamethasone treatment were directly linked to clinical outcome, since the reversal of pathogenic signatures and induction of glucocorticoid response genes were enriched in patients who survived the disease in response to dexamethasone treatment. Cellular responsiveness of circulating monocytes was thus identified as a correlate of clinical response to dexamethasone treatment. Changes in monocyte transcriptomes could also be linked to epigenetic alterations highlighting early differences in monocytes of dexamethasone responders and non-responders. Further, monocyte single-cell transcriptome-derived signatures were enriched in whole blood transcriptomes from patients with fatal outcome in two independent cohorts, highlighting the potential clinical value for early identification of non-responders who are refractory to dexamethasone treatment. Overall, our findings indicate that the life-saving effects of dexamethasone in COVID-19 patients are linked to a specific immunomodulatory effect based on the reversion of monocyte dysregulation. Our study elucidates the potential mechanism of action of one of the most efficient and cost-effective drugs for the treatment of COVID-19. It further highlights the potential of single-cell omics for monitoring target engagement of immunomodulatory drugs and for the stratification of patients for precision medicine approaches.","study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-12-11T16:11:34.254489+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007461","title":"Knoll et al.: The life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation","description":"Following the demonstration of its life-saving effect in clinical trials, dexamethasone quickly became standard-of-care in the treatment of severe COVID-19. Beneficial effects were reported for patients requiring supplemental oxygen or invasive mechanical ventilation. Yet, a substantial proportion of patients still progressed to a critical condition or succumbed to the disease, despite timely initiation of glucocorticoid treatment. No molecular or cellular correlate of this beneficial treatment response has been defined. Here, we identify distinct cellular and molecular changes in circulating immune cells in patients with COVID-19 elicited in response to dexamethasone treatment. The most profound transcriptional changes in response to dexamethasone treatment were noted in monocytes and in B cells. In monocytes, we observed a reversal of hallmark signatures previously associated with COVID-19 severity, and the induction of a specific monocyte substate enriched in glucocorticoid response gene expression which we here refer to as dexamethasone response cluster. Molecular responses to dexamethasone treatment were directly linked to clinical outcome, since the reversal of pathogenic signatures and induction of glucocorticoid response genes were enriched in patients who survived the disease in response to dexamethasone treatment. Cellular responsiveness of circulating monocytes was thus identified as a correlate of clinical response to dexamethasone treatment. Changes in monocyte transcriptomes could also be linked to epigenetic alterations highlighting early differences in monocytes of dexamethasone responders and non-responders. Further, monocyte single-cell transcriptome-derived signatures were enriched in whole blood transcriptomes from patients with fatal outcome in two independent cohorts, highlighting the potential clinical value for early identification of non-responders who are refractory to dexamethasone treatment. Overall, our findings indicate that the life-saving effects of dexamethasone in COVID-19 patients are linked to a specific immunomodulatory effect based on the reversion of monocyte dysregulation. Our study elucidates the potential mechanism of action of one of the most efficient and cost-effective drugs for the treatment of COVID-19. It further highlights the potential of single-cell omics for monitoring target engagement of immunomodulatory drugs and for the stratification of patients for precision medicine approaches.","abstract":"Following the demonstration of its life-saving effect in clinical trials, dexamethasone quickly became standard-of-care in the treatment of severe COVID-19. Beneficial effects were reported for patients requiring supplemental oxygen or invasive mechanical ventilation. Yet, a substantial proportion of patients still progressed to a critical condition or succumbed to the disease, despite timely initiation of glucocorticoid treatment. No molecular or cellular correlate of this beneficial treatment response has been defined. Here, we identify distinct cellular and molecular changes in circulating immune cells in patients with COVID-19 elicited in response to dexamethasone treatment. The most profound transcriptional changes in response to dexamethasone treatment were noted in monocytes and in B cells. In monocytes, we observed a reversal of hallmark signatures previously associated with COVID-19 severity, and the induction of a specific monocyte substate enriched in glucocorticoid response gene expression which we here refer to as dexamethasone response cluster. Molecular responses to dexamethasone treatment were directly linked to clinical outcome, since the reversal of pathogenic signatures and induction of glucocorticoid response genes were enriched in patients who survived the disease in response to dexamethasone treatment. Cellular responsiveness of circulating monocytes was thus identified as a correlate of clinical response to dexamethasone treatment. Changes in monocyte transcriptomes could also be linked to epigenetic alterations highlighting early differences in monocytes of dexamethasone responders and non-responders. Further, monocyte single-cell transcriptome-derived signatures were enriched in whole blood transcriptomes from patients with fatal outcome in two independent cohorts, highlighting the potential clinical value for early identification of non-responders who are refractory to dexamethasone treatment. Overall, our findings indicate that the life-saving effects of dexamethasone in COVID-19 patients are linked to a specific immunomodulatory effect based on the reversion of monocyte dysregulation. Our study elucidates the potential mechanism of action of one of the most efficient and cost-effective drugs for the treatment of COVID-19. It further highlights the potential of single-cell omics for monitoring target engagement of immunomodulatory drugs and for the stratification of patients for precision medicine approaches.","study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-26T17:30:45.141615+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007462","title":"Relation between transcriptome, karyotype and age in cases of sex chromosome aneuploidies.","description":"Why women live longer than men is still an open question in human biology. Sex chromosomes have been proposed to play a role in the observed sex gap in longevity, and the Y male chromosome has been suspected of having a potential toxic genomic impact on male longevity. It has been hypothesized that transposable element (TE) repression declines with age, potentially leading to detrimental effects such as somatic mutations and disrupted gene expression, which may accelerate the aging process. Given that the Y chromosome is rich in repeats, age-related increases in TE expression could be more pronounced in males, likely contributing to their reduced longevity compared to females. In this work, we first studied whether TE expression is associated with the number of sex chromosomes in humans. We analyzed blood transcriptomic data obtained from individuals of different karyotype compositions: 46,XX females (normal female karyotype), 46,XY males (normal male karyotype), as well as males with abnormal karyotypes, such as 47,XXY, and 47,XYY.","abstract":"Why women live longer than men is still an open question in human biology. Sex chromosomes have been proposed to play a role in the observed sex gap in longevity, and the Y male chromosome has been suspected of having a potential toxic genomic impact on male longevity. It has been hypothesized that transposable element (TE) repression declines with age, potentially leading to detrimental effects such as somatic mutations and disrupted gene expression, which may accelerate the aging process. Given that the Y chromosome is rich in repeats, age-related increases in TE expression could be more pronounced in males, likely contributing to their reduced longevity compared to females. In this work, we first studied whether TE expression is associated with the number of sex chromosomes in humans. We analyzed blood transcriptomic data obtained from individuals of different karyotype compositions: 46,XX females (normal female karyotype), 46,XY males (normal male karyotype), as well as males with abnormal karyotypes, such as 47,XXY, and 47,XYY.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-25T10:34:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007463","title":"Establishment and characterization of a new Pseudomonas aeruginosa infection model using 2D airway organoids and dual RNA sequencing","description":null,"abstract":"Pseudomonas aeruginosa is a Gram-negative bacterium that is notorious for infections in the airway of cystic fibrosis (CF) subjects. Often, these infections become chronic, leading to higher morbidity and mortality rates. Bacterial quorum sensing (QS) coordinates the expression of virulence factors and the formation of biofilms at a population level. QS has become the focus of attention for development of alternatives to antimicrobials targeting P. aeruginosa infections. However, a better understanding of the bacteria-host interaction, and the role of QS in infection, is required. In this study, we set up a new P. aeruginosa infection model, using 2D airway organoids derived from healthy and CF individuals. Using dual RNA-sequencing, we dissected their interaction, focusing on the role of QS. As expected, P. aeruginosa induced epithelial inflammation. However, QS signaling did not affect the epithelial airway cells. The epithelium influenced several infection-related processes of P. aeruginosa, including metabolic changes, induction of type 3 and type 6 secretion systems (T3SS and T6SS), and increased expression of antibiotic resistance genes, including mexXY efflux pump and several porins. Interestingly, the epithelium influenced the regulation by QS of the type 2 (T2SS) and T6SS. Finally, we compared our model with in vivo P. aeruginosa transcriptomic datasets, from samples directly isolated from the airways of CF subjects. This shows that our model recapitulates important aspects of in vivo infection, like enhanced denitrification, betaine/choline metabolism, increased antibiotic resistance, as well as an overall decrease of motility-related genes. This relevant infection model is interesting for future investigations, helping to reduce the burden of P. aeruginosa infections in CF.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007464","title":"Spatiotemporal evolution and inter-patient heterogeneity in primary and recurrent/metastatic head and neck squamous cell carcinoma","description":"Head and neck cancer squamous cell carcinomas (HNSCCs) are heterogeneous in terms of origin and aetiology. In addition, there is uncertainty about the spatiotemporal genetic evolution from initial diagnosis to recurrence/metastasis (R/M) after primary treatments and further disease progression following systemic treatment. Changes in the genetic profile have implications on the selection of appropriate treatments for patients, especially in the era of targeted therapies and immunotherapies. Here, we analysed a cohort of 11 HNSCC patients with metachronous R/M, among whom nine had paired primary and R/M samples suitable for next-generation sequencing (multiple R/M samples collected at different time points were available for some of the patients). At the genomic level, the R/M samples shared a fraction of the somatic single nucleotide variants (SNVs) with the index primary tumours, but they also acquired many additional mutations, while losing only a few others. A similar behaviour was also observed when examining the changes of mutational signatures between primary and R/M samples. Overall, R/M appeared thus more genetically diverse than the respective primary tumours. The transcriptomic analysis showed that R/M samples had lower immune cell infiltration and several genes related to immune response were significantly downregulated compared to the primary samples. Our results underline the importance of analysing multiple samples per patient to obtain a more complete picture of the patient’s tumour and advocates a re-biopsy in the event of R/M and treatment failure, in order to select the most appropriate therapeutic strategy.","abstract":"Head and neck cancer squamous cell carcinomas (HNSCCs) are heterogeneous in terms of origin and aetiology. In addition, there is uncertainty about the spatiotemporal genetic evolution from initial diagnosis to recurrence/metastasis (R/M) after primary treatments and further disease progression following systemic treatment. Changes in the genetic profile have implications on the selection of appropriate treatments for patients, especially in the era of targeted therapies and immunotherapies. Here, we analysed a cohort of 11 HNSCC patients with metachronous R/M, among whom nine had paired primary and R/M samples suitable for next-generation sequencing (multiple R/M samples collected at different time points were available for some of the patients). At the genomic level, the R/M samples shared a fraction of the somatic single nucleotide variants (SNVs) with the index primary tumours, but they also acquired many additional mutations, while losing only a few others. A similar behaviour was also observed when examining the changes of mutational signatures between primary and R/M samples. Overall, R/M appeared thus more genetically diverse than the respective primary tumours. The transcriptomic analysis showed that R/M samples had lower immune cell infiltration and several genes related to immune response were significantly downregulated compared to the primary samples. Our results underline the importance of analysing multiple samples per patient to obtain a more complete picture of the patient’s tumour and advocates a re-biopsy in the event of R/M and treatment failure, in order to select the most appropriate therapeutic strategy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-25T14:07:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007465","title":"BCL3-rearrangements in B-cell lymphoid neoplasms occur in two breakpoint clusters associated with different diseases","description":null,"abstract":"Whole-genome sequencing, RNA-seq and DNA methylation data of B-cell lymphoid neoplasms with BCL3 rearrangement.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-25T18:11:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007466","title":"Effective reprogramming of patient-derived M2-polarized glioblastoma-associated microglia/macrophages by treatment with GW2580","description":"Purpose: Targeting immunosuppressive and pro-tumorigenic glioblastoma-associated macrophages and microglial cells (GAMs) has great potential to improve patient outcomes. Colony stimulating factor-1 receptor (CSF1R) has emerged as a promising target for reprogramming anti-inflammatory M2-like GAMs. However, treatment data on patient-derived, tumor-educated GAMs and their influence on the adaptive immunity are lacking. \nExperimental Design: CD11b+-GAMs freshly isolated from patient tumors were treated with CSF1R-targeting drugs PLX3397, BLZ945, and GW2580. Phenotypical changes upon treatment were assessed using RNAseq. Changes in GAM activation were confirmed in a complex patient-derived 3D tumor organoid model serving as a tumor avatar. \nResults: The most effective reprogramming of GAMs was observed upon GW2580 treatment, which led to the downregulation of M2-related markers, IL-6, and IL-10, ERK1/2 and MAPK signaling pathways, while M1-like markers and gene set enrichment indicating activated MHC-II presentation were substantially increased. Moreover, treatment of patient-derived glioblastoma organoids with GW2580 confirmed successful reprogramming.","abstract":"Purpose: Targeting immunosuppressive and pro-tumorigenic glioblastoma-associated macrophages and microglial cells (GAMs) has great potential to improve patient outcomes. Colony stimulating factor-1 receptor (CSF1R) has emerged as a promising target for reprogramming anti-inflammatory M2-like GAMs. However, treatment data on patient-derived, tumor-educated GAMs and their influence on the adaptive immunity are lacking. \nExperimental Design: CD11b+-GAMs freshly isolated from patient tumors were treated with CSF1R-targeting drugs PLX3397, BLZ945, and GW2580. Phenotypical changes upon treatment were assessed using RNAseq. Changes in GAM activation were confirmed in a complex patient-derived 3D tumor organoid model serving as a tumor avatar. \nResults: The most effective reprogramming of GAMs was observed upon GW2580 treatment, which led to the downregulation of M2-related markers, IL-6, and IL-10, ERK1/2 and MAPK signaling pathways, while M1-like markers and gene set enrichment indicating activated MHC-II presentation were substantially increased. Moreover, treatment of patient-derived glioblastoma organoids with GW2580 confirmed successful reprogramming.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-26T11:11:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007467","title":"AML FLT3 TCR study","description":"We identified a T-cell receptor (TCR) reactive to the recurrent FLT3 D835Y mutation in the tyrosine-kinase domain frequently expressed in acute myeloid leukemia (AML). To validate the TCRs' elimination efficacy of leukemic cells, we transplanted human AML cells with FLT3 D835Y mutation into NSG-SGM3 mice and treated either with TCR FLT3 D835Y redirected T cells, or control TCR (TCR 1G4). After treatment, we performed flow sorting of human AML cells from the mice (mCD45-hCD45+hCD3-hCD19-) and compared to primary AML blasts (hCD3-hCD19-) and primary T cells (hCD3+hCD8+orhCD4+hCD19-hCD33-) by whole-exome sequencing.","abstract":"We identified a T-cell receptor (TCR) reactive to the recurrent FLT3 D835Y mutation in the tyrosine-kinase domain frequently expressed in acute myeloid leukemia (AML). To validate the TCRs' elimination efficacy of leukemic cells, we transplanted human AML cells with FLT3 D835Y mutation into NSG-SGM3 mice and treated either with TCR FLT3 D835Y redirected T cells, or control TCR (TCR 1G4). After treatment, we performed flow sorting of human AML cells from the mice (mCD45-hCD45+hCD3-hCD19-) and compared to primary AML blasts (hCD3-hCD19-) and primary T cells (hCD3+hCD8+orhCD4+hCD19-hCD33-) by whole-exome sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-07-27T08:48:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007468","title":"Origin of residual tumor masses in BRCA1/2-driven ovarian carcinomas treated by neoadjuvant chemotherapy: selection of preexisting BRCA1/2-proficient tumor cells but not the gain of second ORF-restoring mutation","description":null,"abstract":"Tubo-ovarian carcinomas (OCs) are highly sensitive to platinum-based neoadjuvant chemotherapy (NACT) but almost never demonstrate complete pathologic response. We analyzed paired primary and residual tumor tissues from 30 patients with hereditary BRCA1/2-driven OCs who were treated by carboplatin/paclitaxel NACT. BRCA1/2 and TP53 genes were analyzed by the next-generation sequencing (NGS). The ratio between TP53 mutation-specific vs. wild-type reads was considered to monitor the proportion of tumor and non-tumor cells in the tissue sample, and the ratio between BRCA1/2 mutated and wild-type reads was used to estimate the presence of cells with the loss or retention of heterozygosity (LOH or ROH, respectively).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007469","title":"Comprehensive Characterization of Early Relapse and End-Stage Relapsed Refractory Multiple Myeloma (HIPO K08K/H067/H021+nonHIPO)","description":null,"abstract":"Treatments incorporating autologous transplantation (ASCT), proteasome inhibitors (PIs), and immunomodulatory drugs (IMIDs) induce deep and durable remissions in most multiple myeloma (MM) patients, resulting in prolonged survival. Yet, patients who suffer from early relapse within 2 years of treatment initiation or become refractory to PIs and IMIDs still have a dismal outcome. The mutational landscape in early relapsed MM (ERMM) and relapsed/refractory MM (RRMM) has been comprehensively described. Several aberrations are associated with these two types of high-risk disease but little is known about the biological difference between them. To this end, we have comparatively and sequentially analyzed whole genome and RNA sequencing data from ERMM, RRMM and newly diagnosed MM patients (NDMM) without relapse.\nAccording to our results ERMM and RRMM are biologically distinct entities of MM. While ERMM is characterized by inactivation of tumor suppressors and upregulation of gene sets associated with hypoxia and glycolysis, RRMM shows mutations in multiple gene networks, upregulation of ribosomal protein pseudogenes with unknown function and a signature linked to defective DNA repair, suggesting multifactorial mechanisms that lead from first relapse to end-stage relapsed refractory disease. Comparing paired samples, we did not observe major difference in evolution patterns between ERMM and RRMM. Yet, the low prevalence of the melphalan MM1 signature in ERMM suggests selection of pre-existing clones in this entity. In contrast, single tumor cells exposed to melphalan are often the precursors of clones dominating at the RRMM stage, indicating that first-line ASCT has a long-term effect on MM evolution.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-23T00:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007470","title":"Rapid, economical diagnostic classification of ATRT molecular subgroup using NanoString nCounter platform","description":null,"abstract":"Rapid, cost-effective, and accurate ATRT subgrouping assay","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007471","title":"SARS-CoV2 mRNA-vaccination-induced Immunological Memory in Human Non-Lymphoid and Lymphoid Tissues","description":null,"abstract":"SARS-CoV2 mRNA vaccination-induced CD4+ Th cells were isolated based on activation marker expression from human bone marrow (n=3), lung (n=5), liver (n=4) and paired blood samples (to liver donors, n=4) of virus-naive vaccinees after Spike peptide mix stimulation in vitro. The 10X platform was used for single cell transcriptome analysis, along with T cell receptor clonotype analysis in a total of 1985 cells. Samples were sequenced on a NovaSeq 6000 (Illumina).","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007472","title":"scATAC-seq and combined scRNA-seq of the human first trimester neurodevelopment","description":null,"abstract":"Analysis of the chromatin landscape and paired gene expression across the developing human brain to provide a comprehensive single cell atlas during the first trimester (6 -13 post-conceptional weeks).","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-03T15:45:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007473","title":"RNAseq data of phamacotyping samples","description":null,"abstract":"Leukemia can arise at different nodes of the hematopoietic differentiation hierarchy, but the impact of the state of developmental arrest on drug sensitivity is unclear. Applying network-based analyses to single-cell transcriptomes of human B cells, we first defined genome-wide signaling circuitry for each B-cell differentiation stage. Using this reference, we comprehensively mapped the developmental states of 203 childhood B-cell acute lymphoblastic leukemia (B-ALL) and revealed its strong correlation with leukemia sensitivity to L-asparaginase, a common chemotherapeutic agent. Further single-cell-multi-omic analyses of primary blasts from B-ALL patients revealed marked intra-leukemia heterogeneity in L-asparaginase response: resistance linked to pre-pro-B-like cells and sensitivity to pro-B-like population. By targeting BCL2, the key driver genes in pre-pro-B-like cell signaling network, venetoclax significantly potentiated asparaginase efficacy in vitro and in vivo. We demonstrate a single-cell systems pharmacology framework to predict effective combination therapies based on intra-leukemia heterogeneity in developmental state, with broad applications beyond B-ALL.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007474","title":"Epithelioid haemangioendothelioma (EHE) case series from the Stafford Fox Rare Cancer Program","description":"Nine EHE cases with comprehensive histologic and molecular profiling from the Walter and Eliza Hall Institute of Medical Research Stafford Fox Rare Cancer Program were collated via nation-wide referral to the Australian Rare Cancer Portal. Molecular analysis of RNA, DNA or both was possible in seven of nine cases. Survival was highly variable and unrelated to molecular profile.  DNA sequences for two cases are deposited here.","abstract":"Nine EHE cases with comprehensive histologic and molecular profiling from the Walter and Eliza Hall Institute of Medical Research Stafford Fox Rare Cancer Program were collated via nation-wide referral to the Australian Rare Cancer Portal. Molecular analysis of RNA, DNA or both was possible in seven of nine cases. Survival was highly variable and unrelated to molecular profile.  DNA sequences for two cases are deposited here.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-04T02:11:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007475","title":"Ultra-fast deep-learned pediatric CNS tumor classification.","description":"The primary treatment of CNS tumors starts with a neurosurgical resection in order to obtain tumor tissue for diagnosis and to reduce tumor load and mass effect. The neurosurgeon has to decide between radical resection versus a more conservative strategy to prevent surgical morbidity. The prognostic impact of a radical resection varies between tumor types. However due to a lack of pre-operative tissue-based diagnostics, limited knowledge of the precise tumor type is available at the time of surgery. Current standard practice includes preoperative imaging and intraoperative histological analysis, but these are not always conclusive. After surgery, histopathological and molecular tests are performed to diagnose the precise tumor type. The results may indicate that an additional surgery is needed or that the initial surgery could have been less radical. Using rapid Nanopore sequencing, a sparse methylation profile can be directly obtained during surgery, making it ideally suited to enable intraoperative diagnostics. We developed a state-of-the-art neural-network approach called Sturgeon, to deliver trained models that are lightweight and universally applicable across patients and sequencing depths. We demonstrate our method to be accurate and fast enough to provide a correct diagnosis with as little as 20 to 40 minutes of sequencing data in 45 out of 49 pediatric samples, and inconclusive results in the other four. In four intraoperative cases we achieved a turnaround time of 60-90 minutes from sample biopsy to result; well in time to impact surgical decision making. We conclude that machine-learned diagnosis based on intraoperative sequencing can assist neurosurgical decision making, allowing neurological comorbidity to be avoided or preventing additional surgeries.","abstract":"The primary treatment of CNS tumors starts with a neurosurgical resection in order to obtain tumor tissue for diagnosis and to reduce tumor load and mass effect. The neurosurgeon has to decide between radical resection versus a more conservative strategy to prevent surgical morbidity. The prognostic impact of a radical resection varies between tumor types. However due to a lack of pre-operative tissue-based diagnostics, limited knowledge of the precise tumor type is available at the time of surgery. Current standard practice includes preoperative imaging and intraoperative histological analysis, but these are not always conclusive. After surgery, histopathological and molecular tests are performed to diagnose the precise tumor type. The results may indicate that an additional surgery is needed or that the initial surgery could have been less radical. Using rapid Nanopore sequencing, a sparse methylation profile can be directly obtained during surgery, making it ideally suited to enable intraoperative diagnostics. We developed a state-of-the-art neural-network approach called Sturgeon, to deliver trained models that are lightweight and universally applicable across patients and sequencing depths. We demonstrate our method to be accurate and fast enough to provide a correct diagnosis with as little as 20 to 40 minutes of sequencing data in 45 out of 49 pediatric samples, and inconclusive results in the other four. In four intraoperative cases we achieved a turnaround time of 60-90 minutes from sample biopsy to result; well in time to impact surgical decision making. We conclude that machine-learned diagnosis based on intraoperative sequencing can assist neurosurgical decision making, allowing neurological comorbidity to be avoided or preventing additional surgeries.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-04T13:42:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007476","title":"Genomic Profiling Reveals Chemotherapy-Related Clonal Hematopoiesis in High-Grade Serous Ovarian Cancer","description":null,"abstract":"Clonal hematopoiesis (CH) is identified as the presence of clonal populations of hematopoietic stem cells (HSC) that, due to fitness advance, might give rise to clonally expanded populations, and eventually hematological malignancies. Clonal hematopoiesis of indeterminate potential (CHIP) is instead defined as the outgrowth of a single HSC clone driven by acquired somatic mutation, in the absence of hematological abnormalities. According to the current literature, CHIP mutations occur with an allele frequency of at least 2% in peripheral blood (in the absence of a morphological variation in blood cells). This definition, even if shared by many, is still incomplete, due to the possibility for less frequent mutations of giving rise to hematopoietic clones. Previous studies have indicated the association of CH with aging and with a higher risk of developing secondary hematologic malignancies in cancer patients treated with chemotherapy agents; on the other hand, less is known about the correlation between presence of a CHIP mutation and the outcome of chemotherapy. To investigate this specific issue, we performed an in depth characterization of CHIP variants on a highly selected group of patients with high-grade serous ovarian cancer (HGSC) before and after neoadjuvant chemotherapy; while previous CHIP studies are largely based on known hematologic genes and used targeted gene panels, our study aims at discovering novel candidate CHIP mutations, considering a lower variant allele frequency (VAF). Comprehensive ultra-high-depth whole exome sequencing using unique molecular barcode technology was performed on plasma-derived cfDNA and matched white blood cells (WBC) DNA from pre- (n=20) and post-NACT (n=20) samples of patients with HGSC who showed excellent (n=5, ER) or poor response (n=5, PR) to NACT.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007477","title":"Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations","description":null,"abstract":"Esophageal squamous cell carcinoma (ESCC) has a high disease burden in sub-Saharan Africa and has a very poor prognosis. Genome-wide association studies of ESCC in predominantly East Asian populations indicate a substantial genetic contribution to its etiology, but no genome-wide studies have been done in populations of African ancestry. Here we report a genome-wide association study in 1,686 African ESCC patients and 3,217 population-matched controls to investigate its genetic etiology.  A novel, genome-wide significant risk locus was identified on chromosome 9 upstream of FAM120A (rs12379660, P=4.58x10-8, odds ratio=1.28, 95% confidence interval=1.22-1.34), and a potential African-specific risk locus was identified on chromosome 2 (rs142741123, P=5.49x10-8) within MYO1B. FAM120A is a component of oxidative stress-induced survival signals, and the associated variants at the FAM120A locus co-localized with highly significant cis-eQTLs in FAM120AOS in both esophageal mucosa and esophageal muscularis tissue. A trans-ethnic meta-analysis was then performed with the African ESCC study and a Chinese ESCC study in a combined total of 3,699 ESCC cases and 5,918 controls which identified three genome-wide significant loci on chromosome 9 at FAM120A (rs12379660, Pmeta=9.36x10-10), chromosome 10 at PLCE1 (rs7099485, Pmeta=1.48x10-8) and chromosome 22 at CHEK2 (rs1033667, Pmeta=1.47x10-9). This indicates the existence of both shared and distinct genetic risk loci for ESCC in African and Asian populations.   Our genome-wide association study of ESCC conducted in a population of African ancestry indicates a substantial genetic contribution to ESCC risk in Africa.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-08T09:44:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007478","title":"Single cell RNA sequencing of cerebrospinal fluid","description":"Single-cell RNA sequencing of cells isolated from cerebrospinal fluid from 81 individuals with multiple sclerosis (n=33) or other neurological disease (n=48) using 10x Genomics 3’ expression (v2 chemistry).","abstract":"Single-cell RNA sequencing of cells isolated from cerebrospinal fluid from 81 individuals using 10X Genomics 3’ expression (v2 chemistry).","study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-26T17:35:06.939008+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007479","title":"DLBCLR","description":"Evaluating gene expression in DLBCL using a quantitative nuclease protection assay","abstract":"Evaluating gene expression in DLBCL using a quantitative nuclease protection assay","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-08T20:05:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007480","title":"ROBUST (NCT02285062)","description":null,"abstract":"Efficacy and Safety Study of Lenalidomide Plus R-CHOP Chemotherapy Versus Placebo Plus R-CHOP Chemotherapy in Untreated ABC Type Diffuse Large B-cell Lymphoma","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007481","title":"Oncoprint GSCCs","description":"Glioblastoma (GBM) remains the most malignant primary brain tumor, with a median survival rarely exceeding 2 years. Tumor heterogeneity and an immunosuppressive microenvironment are key factors contributing to the poor response rates of current therapeutic approaches. GBM-associated macrophages (GAMs) often exhibit immunosuppressive features that promote tumor progression. However, their dynamic interactions with GBM tumor cells remain poorly understood. Here, we used patient-derived GBM stem cell cultures and combined single-cell RNA sequencing of GAM-GBM co-cultures and real-time in vivo monitoring of GAM-GBM interactions in orthotopic zebrafish xenograft models to provide insight into the cellular, molecular, and spatial heterogeneity. Our analyses revealed substantial heterogeneity across GBM patients in GBM-induced GAM polarization and the ability to attract and activate GAMs – features that correlated with patient survival. Differential gene expression analysis, immunohistochemistry on original tumor samples, and knock-out experiments in zebrafish subsequently identified LGALS1 as a primary regulator of immunosuppression. Overall, our work highlights that GAM-GBM interactions can be studied in a clinically relevant way using co-cultures and avatar models, while offering new opportunities to identify promising immune-modulating targets.","abstract":"Glioblastoma (GBM) remains the most malignant primary brain tumor, with a median survival rarely exceeding 2 years. Tumor heterogeneity and an immunosuppressive microenvironment are key factors contributing to the poor response rates of current therapeutic approaches. GBM-associated macrophages (GAMs) often exhibit immunosuppressive features that promote tumor progression. However, their dynamic interactions with GBM tumor cells remain poorly understood. Here, we used patient-derived GBM stem cell cultures and combined single-cell RNA sequencing of GAM-GBM co-cultures and real-time in vivo monitoring of GAM-GBM interactions in orthotopic zebrafish xenograft models to provide insight into the cellular, molecular, and spatial heterogeneity. Our analyses revealed substantial heterogeneity across GBM patients in GBM-induced GAM polarization and the ability to attract and activate GAMs – features that correlated with patient survival. Differential gene expression analysis, immunohistochemistry on original tumor samples, and knock-out experiments in zebrafish subsequently identified LGALS1 as a primary regulator of immunosuppression. Overall, our work highlights that GAM-GBM interactions can be studied in a clinically relevant way using co-cultures and avatar models, while offering new opportunities to identify promising immune-modulating targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-09T08:53:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007482","title":"Single-cell profiling of co-cultures of GSCCs and macrophages","description":"Glioblastoma (GBM) remains the most malignant primary brain tumor, with a median survival rarely exceeding 2 years. Tumor heterogeneity and an immunosuppressive microenvironment are key factors contributing to the poor response rates of current therapeutic approaches. GBM-associated macrophages (GAMs) often exhibit immunosuppressive features that promote tumor progression. However, their dynamic interactions with GBM tumor cells remain poorly understood. Here, we used patient-derived GBM stem cell cultures and combined single-cell RNA sequencing of GAM-GBM co-cultures and real-time in vivo monitoring of GAM-GBM interactions in orthotopic zebrafish xenograft models to provide insight into the cellular, molecular, and spatial heterogeneity. Our analyses revealed substantial heterogeneity across GBM patients in GBM-induced GAM polarization and the ability to attract and activate GAMs – features that correlated with patient survival. Differential gene expression analysis, immunohistochemistry on original tumor samples, and knock-out experiments in zebrafish subsequently identified LGALS1 as a primary regulator of immunosuppression. Overall, our work highlights that GAM-GBM interactions can be studied in a clinically relevant way using co-cultures and avatar models, while offering new opportunities to identify promising immune-modulating targets.","abstract":"Glioblastoma (GBM) remains the most malignant primary brain tumor, with a median survival rarely exceeding 2 years. Tumor heterogeneity and an immunosuppressive microenvironment are key factors contributing to the poor response rates of current therapeutic approaches. GBM-associated macrophages (GAMs) often exhibit immunosuppressive features that promote tumor progression. However, their dynamic interactions with GBM tumor cells remain poorly understood. Here, we used patient-derived GBM stem cell cultures and combined single-cell RNA sequencing of GAM-GBM co-cultures and real-time in vivo monitoring of GAM-GBM interactions in orthotopic zebrafish xenograft models to provide insight into the cellular, molecular, and spatial heterogeneity. Our analyses revealed substantial heterogeneity across GBM patients in GBM-induced GAM polarization and the ability to attract and activate GAMs – features that correlated with patient survival. Differential gene expression analysis, immunohistochemistry on original tumor samples, and knock-out experiments in zebrafish subsequently identified LGALS1 as a primary regulator of immunosuppression. Overall, our work highlights that GAM-GBM interactions can be studied in a clinically relevant way using co-cultures and avatar models, while offering new opportunities to identify promising immune-modulating targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-09T08:53:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007483","title":"Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of DYRK1A","description":"We describe recurrent chromothripsis and structural variation of chromosome 21 in a subset of patients in blast phase of a myeloproliferative neoplasm (BP-MPN), which alongside other structural variants leads to amplification of a region of chromosome 21 in ~25% of patients (‘chr21amp’). Chr21amp BP-MPN has a particularly aggressive and treatment-resistant phenotype. Here we provide high-depth whole genome sequencing (WGS) in five chr21amp BP-MPN cases, to a median coverage of 81x [range 77-86] and purity 79% [range 58-88%].","abstract":"We describe recurrent chromothripsis and structural variation of chromosome 21 in a subset of patients in blast phase of a myeloproliferative neoplasm (BP-MPN), which alongside other structural variants leads to amplification of a region of chromosome 21 in ~25% of patients (‘chr21amp’). Chr21amp BP-MPN has a particularly aggressive and treatment-resistant phenotype. Here we provide high-depth whole genome sequencing (WGS) in five chr21amp BP-MPN cases, to a median coverage of 81x [range 77-86] and purity 79% [range 58-88%].","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007484","title":"Discrepancies in Tumour Mutation Burden (TMB) reporting from sequential Endobronchial ultrasound trans bronchial needle aspiration (EBUS TBNA) samples within single lymph node stations","description":"Introduction: Tumour Mutation Burden (TMB) is a potential biomarker for immune therapies. Identifying factors that may affect TMB prediction is key to its utility as biomarker for treatment options. Here we investigated parameters that might affect TMB using cytology smears obtained from endobronchial ultrasound transbronchial needle aspiration (EBUS TBNA)-sampled malignant lymph nodes, which are often the only diagnostic samples collected in patients with advanced lung cancer.\nMethods: Individual Diff-Quik cytology smears were prepared for each needle pass from the same enlarged malignant mediastinal lymph nodes. DNA extracted from smears of each pass underwent sequencing using a large gene panel sequencing (TSO500, Illumina). TMB was estimated for each individual needle pass using the TSO500 Local App v. 2.0 (Illumina).\nResults: Twenty patients had two or more Diff-Quik smears (total 45 smears) which passed sequencing quality control. Average TMB for all smears was 8.7 ± 5.0 mutations per megabase (Mb). Sixteen of the 20 patients had paired samples with minimal differences in TMB score (average difference 1.3 ± 0.85). Paired samples from 13 patients had concordant TMB in terms of scores being below or above a threshold of 10 mutations/Mb. Samples from seven patients had discrepant TMB, with four cases in particular exhibiting an average difference of 11.3 ± 2.7 mutations/Mb. Factors affecting TMB calling involved tumour content of the samples, the amount of DNA used in sequencing as well as bone fide intra tumour heterogeneity between paired samples. \nConclusions: TMB assessment is feasible from EBUS-TBNA derived Diff-Quik slides from a single needle pass. Repeated samples of one or more lymph nodes have minimal variation in TMB in most cases (80%), suggesting accuracy of the test overall. To enhance accuracy of the result, care should be taken in relation to the tumour content of the cytology smear. Further, clinicians should be aware that even slight differences in lymph node site selection could give rise to variable genomics and discrepant TMB due to tumour heterogeneity. Therefore, it would be reasonable for multi-lymph node site analysis of TMB to be performed using EBUS TBNA aspirates from different easily accessible lymph nodes. Further investigations need to determine whether these samples should be combined as one sample or tested separately.","abstract":"Introduction: Tumour Mutation Burden (TMB) is a potential biomarker for immune therapies. Identifying factors that may affect TMB prediction is key to its utility as biomarker for treatment options. Here we investigated parameters that might affect TMB using cytology smears obtained from endobronchial ultrasound transbronchial needle aspiration (EBUS TBNA)-sampled malignant lymph nodes, which are often the only diagnostic samples collected in patients with advanced lung cancer.\nMethods: Individual Diff-Quik cytology smears were prepared for each needle pass from the same enlarged malignant mediastinal lymph nodes. DNA extracted from smears of each pass underwent sequencing using a large gene panel sequencing (TSO500, Illumina). TMB was estimated for each individual needle pass using the TSO500 Local App v. 2.0 (Illumina).\nResults: Twenty patients had two or more Diff-Quik smears (total 45 smears) which passed sequencing quality control. Average TMB for all smears was 8.7 ± 5.0 mutations per megabase (Mb). Sixteen of the 20 patients had paired samples with minimal differences in TMB score (average difference 1.3 ± 0.85). Paired samples from 13 patients had concordant TMB in terms of scores being below or above a threshold of 10 mutations/Mb. Samples from seven patients had discrepant TMB, with four cases in particular exhibiting an average difference of 11.3 ± 2.7 mutations/Mb. Factors affecting TMB calling involved tumour content of the samples, the amount of DNA used in sequencing as well as bone fide intra tumour heterogeneity between paired samples. \nConclusions: TMB assessment is feasible from EBUS-TBNA derived Diff-Quik slides from a single needle pass. Repeated samples of one or more lymph nodes have minimal variation in TMB in most cases (80%), suggesting accuracy of the test overall. To enhance accuracy of the result, care should be taken in relation to the tumour content of the cytology smear. Further, clinicians should be aware that even slight differences in lymph node site selection could give rise to variable genomics and discrepant TMB due to tumour heterogeneity. Therefore, it would be reasonable for multi-lymph node site analysis of TMB to be performed using EBUS TBNA aspirates from different easily accessible lymph nodes. Further investigations need to determine whether these samples should be combined as one sample or tested separately.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-10T04:16:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007485","title":"Standard_Whole_Exome_Sequencing__AplasticAnaemia_","description":"The somatic mutational landscape of aplastic anaemia will be characterized Standard Whole Exome Sequencing. Samples have been sourced from the Cambridge Biobank.","abstract":"The somatic mutational landscape of aplastic anaemia will be characterized using Standard Whole Exome Sequencing. Samples have been sourced from the Cambridge Biobank.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007486","title":"Subclonal somatic copy number alterations emerge and dominate in recurrent osteosarcoma","description":"Multiple large-scale genomic profiling efforts have been undertaken in osteosarcoma to define the genomic drivers of tumorigenesis, therapeutic response, and disease recurrence. The spatial and temporal intratumor heterogeneity could also play a role in promoting tumor growth and treatment resistance. Here, we conducted longitudinal whole-genome sequencing of 37 tumor samples from eight patients with osteosarcoma that relapsed or became refractory to initial therapy. We found that the chemoresistant population in recurrent osteosarcoma is subclonal at diagnosis, emerges at the time of primary resection due to selective pressure from neoadjuvant chemotherapy, and is characterized by unique oncogenic amplifications.","abstract":"Multiple large-scale genomic profiling efforts have been undertaken in osteosarcoma to define the genomic drivers of tumorigenesis, therapeutic response, and disease recurrence. The spatial and temporal intratumor heterogeneity could also play a role in promoting tumor growth and treatment resistance. Here, we conducted longitudinal whole-genome sequencing of 37 tumor samples from eight patients with osteosarcoma that relapsed or became refractory to initial therapy. We found that the chemoresistant population in recurrent osteosarcoma is subclonal at diagnosis, emerges at the time of primary resection due to selective pressure from neoadjuvant chemotherapy, and is characterized by unique oncogenic amplifications.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-10T15:28:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007487","title":"Optimizing single-cell transcriptomic discrimination of atopic dermatitis versus psoriasis vulgaris","description":"Optimizing single-cell transcriptomic discrimination of atopic dermatitis versus psoriasis vulgaris","abstract":"Optimizing single-cell transcriptomic discrimination of atopic dermatitis versus psoriasis vulgaris","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-10T21:03:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007488","title":"Single cell transcriptomics of human adrenal gland reveal chromosomal alterations in adrenocortical cells","description":"Adrenocortical cells get replenished throughout our lifetime and as such they are a cellular population of high interest in relation to adrenocortical tumours. Single cell transcriptomics of human adrenal gland were performed to identify rare subpopulations of cells, dynamics of cellular turnover and clone expansions in the adrenal cortex. The adrenal gland of this particular individual is characterized by the presence of mutant clone charecterized by aneuploidy in chromosomes 8, 9, 13 and 22,  occupying the zona glomerulosa and zona fasciculata. Differential expression analysis of the mutant cells revealed upregulation of MC2R (adrenocorticotropic hormone receptor), CYP21A2, HSD3B2 genes (enzymes involved in cortisol production). Overall, this donor sample is an example of clonal tissue expansions carrying chromosomal rearrangements that likely impact organ morphology and function but are seemingly benign.","abstract":"Adrenocortical cells get replenished throughout our lifetime and as such they are a cellular population of high interest in relation to adrenocortical tumours. Single cell transcriptomics of human adrenal gland were performed to identify rare subpopulations of cells, dynamics of cellular turnover and clone expansions in the adrenal cortex. The adrenal gland of this particular individual is characterized by the presence of mutant clone charecterized by aneuploidy in chromosomes 8, 9, 13 and 22,  occupying the zona glomerulosa and zona fasciculata. Differential expression analysis of the mutant cells revealed upregulation of MC2R (adrenocorticotropic hormone receptor), CYP21A2, HSD3B2 genes (enzymes involved in cortisol production). Overall, this donor sample is an example of clonal tissue expansions carrying chromosomal rearrangements that likely impact organ morphology and function but are seemingly benign.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-11T12:26:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007489","title":"Sequencing of Ovarian Cancer","description":null,"abstract":"To confirm that our new methylation assay named iMethyl had better predictive power than previous measures such as tumor mutation burden (TMB) and neoantigen load (NeoAg), whole-exome sequencing (n=37) and RNA sequencing (n=36) were also performed in ovarian cancer. The libraries were quantified by Qubit and 2200 Tapestation, and sequenced on an Illumina HiSeq 2500 platform with 2 × 100 bp paired ends. The target coverage for the normal samples and tumor samples was × 50 and x 100, respectively.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007490","title":"Sequencing of Breast Cancer","description":null,"abstract":"To confirm that our new methylation assay named iMethyl had better predictive power than previous measures such as tumor mutation burden (TMB) and neoantigen load (NeoAg), whole-exome sequencing (n=76) and RNA sequencing (n=53) were also performed in breast cancer. The libraries were quantified by Qubit and 2200 Tapestation, and sequenced on an Illumina HiSeq 2500 platform with 2 × 100 bp paired ends. The target coverage for the normal samples and tumor samples was × 50 and x 100, respectively.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007491","title":"Advanced iPSC-CMs maturation by integrating maturation medium, nanopatterning, and electrical stimulation","description":null,"abstract":"The generation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offers an unlimited source of patient-specific human cardiomyocytes. However, the use of iPSC-CM in vitro-models to guide the clinic selection of particular drugs for individual patients remains a vision. A major limitation represents the immature phenotype of iPSC-CMs, which alters their sensitivity towards physiological and pathophysiological stimuli, cardioactive drugs or toxic substances, in comparison to adult cardiomyocytes (CMs). In this study, we aim to generate iPSC-CMs with an advanced maturation state by combining the use of MM with the alignment of the cells on nanopatterned surfaces (NP) and induction of an increased contractile workload by electrical stimulation (ES). Under the combined influence of MM, NP and ES, iPSC-CMs develop a more complex cellular structure, increased mitochondrial content and enhanced electrophysiological properties. Furthermore, the response of iPSC-CMs matured under influence of MM, NP and ES to isoprenaline as well as verapamil differs to less mature iPSC-CMs cultured in B27-medium. Taken together, our results reveal that the combination of MM, NP and ES strongly improves the maturation state of iPSC-CMs and that this advanced maturation state critically affects the cell behavior in functional studies as well as response to cardioactive drugs.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-14T10:15:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007492","title":"A new myeloma subtype defined by undetectable CTCs","description":null,"abstract":"There is evidence suggesting that multiple myeloma (MM) circulating tumor cells (CTCs) are responsible for the disease spreading inside and outside the bone marrow. However, some patients unexpectedly have no CTCs at diagnosis. We hypothesized that the absence of CTCs defines a specific MM subtype with unique clinical and biological features. CTCs were assessed using next-generation flow cytometry in 1,665 patients: 467 monoclonal gammopathy of undetermined significance (MGUS), 346 smoldering (SMM) 652 newly diagnosed (NDMM) and 200 with relapsed/refractory (RRMM) disease enrolled in PETHEMA/GEM studies. The frequency of patients with undetectable CTCs progressively decreased (P &lt;.001) from MGUS (54%) to SMM (21%), NDMM (8%) and RRMM (11%). Undetectable CTCs was an independent prognostic factor associated with inferior risk of progression in SMM (hazard ratio [HR]: 0.38; P =.042), as well as longer progression-free (HR: 0.25; P &lt;.001) and overall survival (HR: 0.24; P =.014) in NDMM. When compared to other NDMM patients, those with undetectable CTCs showed clinical features partially resembling macrofocal disease, as well as different genetic and transcriptional profiles linked to a lower incidence of +1q21 and del(1p32). Together, these results endorse the recognition of patients with undetectable CTCs as a new biological and clinical subtype of MM.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007493","title":"Methylation-based deconvolution of cell-free DNA","description":null,"abstract":"Plasma cell-free DNA (cfDNA) released mainly by dying cells preserves the epigenetic characteristics of its cellular origin and in the presence of cancer part of this may originate from tumour cells. Here we exploit methylation features to estimate tissue contribution to plasma cfDNA sample focused on multi-cancer typing. Our method uses a reference atlas of tissues specific methylation markers to estimate relative contribution of each reference entity in a cfDNA sample thereby aiding in identifying the tissue of origin of the cancer in a cfDNA sample.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-14T15:48:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007494","title":"test","description":null,"abstract":"test","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007495","title":"HCA_Muscle_Adult_Wellcome_RNA_Managed_Access","description":"Transcriptomic analysis of skeletal muscle, to understand the mechanisms of muscle ageing.","abstract":"Teichmann lab from Sanger Institute will perform gene expression analysis on the skeletal muscle biopsies and sections provided by Newcastle University to uncover mechanisms of muscle ageing. In recent years Teichmann lab has established a strong expertise in nuclei isolation, single-nuclei/single-cell RNA-sequencing, ATAC-sequencing and corresponding data analysis from multiple tissues, including human intercostal muscle.Hence, we plan to perform nuclei isolation from the skeletal muscle biopsies followed by singlenuclei RNA-sequencing and ATAC-sequencing. We will process and analyze the following data to uncover the diversity of cell types and myonuclei specific to vastus lateralis muscle and how it changes over time. We will also use the data to uncover cell-type specific changes in gene expression and chromatin accessibility that accompany ageing. Finally, we will use spatial transcriptomic approaches and imaging to place changes in the gene expression and cell type composition with age in the context of the skeletal muscle architecture.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-15T13:34:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007496","title":"Exceptional Outcomes in a Phase Ib Study Combining PARP and MEK Inhibition, With or Without Anti-PD-L1, for BRCA-Wildtype Platinum-Sensitive Recurrent Ovarian Cancer","description":"To evaluate regimens combining PARP and MEK inhibition, with or without PD-L1 inhibition, for BRCA-wildtype platinum-sensitive recurrent ovarian cancer (PSROC).","abstract":"To evaluate regimens combining PARP and MEK inhibition, with or without PD-L1 inhibition, for BRCA-wildtype platinum-sensitive recurrent ovarian cancer (PSROC).","study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007497","title":"RNASeq Javelin head and neck 100","description":null,"abstract":"Immune checkpoint blockade (ICB) has improved patient outcomes in \nmultiple cancers, including head and neck squamous cell carcinomas \n(HNSCC), yet many patients do not benefit. Combination therapies \nintegrating immunotherapy are benefitting patients but the drivers of \nefficacy are not understood.  \nHere we report genomic, microenvironmental, and tumor microbiome \ncorrelates of efficacy to avelumab combined with standard of care \nchemoradiotherapy (CRT) in the phase 3 randomized, double-blinded, \nplacebo-controlled study in patients with locally advanced squamous \ncell carcinoma of the head and neck JAVELIN Head and Neck 100 \n(NCT02952586).","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-16T09:19:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007498","title":"Epigenetic reprogramming shapes monocytes and heterologous T cell derived cytokine responses in BCG vaccination","description":null,"abstract":"Epigenetic reprogramming plays an important role in the development of immune memory characteristics in both innate (trained immunity) and adaptive immune cells following BCG vaccination. However, the influence of dynamic DNA methylation changes on immunological responses after BCG remains poorly understood. To address this, we conducted a longitudinal study in 284 healthy Dutch individuals, profiling genome-wide DNA methylation at baseline, 14 days, and 90 days post- in vivo Bacillus Calmette-Guérin (BCG) vaccination. Distinct patterns of DNA methylation changes emerged in the short and long term after BCG vaccination. Baseline DNA methylation were associated with increased interferon-γ (IFN-γ) production upon Staphylococcus aureus stimulation, with kisspeptin regulation being one of the pathways involved in IFN-γ production. We observed associations between BCG-induced DNA methylation changes and trained immunity responses, including increased IFN-γ and IL-1β production from PBMCs upon S. aureus stimulation. Moreover, DNA methylation changes mediated the impact of genetic variants on trained immunity responses. Sex-specific alterations in DNA methylation were identified after BCG vaccination, along with sex-specific associations with innate immune memory. Our findings highlight BCG-induced immune-related epigenetic memory through dynamic DNA methylation changes, shaping both monocyte and T cell-derived cytokine responses.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-16T10:51:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007499","title":"The genomic echoes of the last Green Sahara on the Fulani and Sahelian people","description":null,"abstract":"By performing high coverage whole genome sequencing of the Sahelian Fulani herders, we confirmed the presence of a non-negligible non-sub-Saharan ancestry component that was further analyzed in the frame of the available ancient DNA data, possibly tracing its origin back to the last Green Sahara 12,000-5,000 years ago.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-16T15:21:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007500","title":"Somatic_mutations_in_DNA_damage_associated_rare_diseases__Duplex_","description":"Genomic instability is a hallmark of ageing. Throughout life, both exogenous and endogenous mutational processes result in distinct damage to our DNA, consequently leading to increased genomic instability with age. Defects in the nucleotide excision repair (NER) pathway, which primarily responds to single-strand mutations, have been found to be associated with increased genome instability. However, they have also been shown to give rise to a number of premature ageing disorders, referred to as progeroid syndromes. Although the origin of these diseases is known, our knowledge about the course of disease is limited. In part, this can be explained by the short-life span of individuals suffering from premature ageing phenotypes, including but not limited to increased cancer risk, attenuated growth, cachexia or neurodegeneration. \n\nIn this study, we propose to investigate the contribution of somatic mutations to DNA damage accumulated in individuals with progeroid syndromes. We will assess the mutation and indel burden in a variety of individuals with alterations in genes such as ATM, FANCA, XPG, ERCC6L6, DNMT3B, ZBTB25, BRCA1, BLM or MSH2 as well as others. Although most of the syndromes show distinct ageing phenotypes, we will systematically analyse DNA extracted from peripheral blood mononuclear cells (PBMCs) and buccal epithelium. Extracted DNA will be utilised for nanorate sequencing, a newly developed duplex sequencing protocol, which will enable us to accurately detect somatic mutations as well as small insertions and deletions (indels), mutational signatures and underlying processes of DNA damage. Overall, we anticipate the proposed study to improve our understanding of the role of somatic mutations in accelerated ageing phenotypes.","abstract":"Genomic instability is a hallmark of ageing. Throughout life, both exogenous and endogenous mutational processes result in distinct damage to our DNA, consequently leading to increased genomic instability with age. Defects in the nucleotide excision repair (NER) pathway, which primarily responds to single-strand mutations, have been found to be associated with increased genome instability. However, they have also been shown to give rise to a number of premature ageing disorders, referred to as progeroid syndromes. Although the origin of these diseases is known, our knowledge about the course of disease is limited. In part, this can be explained by the short-life span of individuals suffering from premature ageing phenotypes, including but not limited to increased cancer risk, attenuated growth, cachexia or neurodegeneration. \n\nIn this study, we propose to investigate the contribution of somatic mutations to DNA damage accumulated in individuals with progeroid syndromes. We will assess the mutation and indel burden in a variety of individuals with alterations in genes such as ATM, FANCA, XPG, ERCC6L6, DNMT3B, ZBTB25, BRCA1, BLM or MSH2 as well as others. Although most of the syndromes show distinct ageing phenotypes, we will systematically analyse DNA extracted from peripheral blood mononuclear cells (PBMCs) and buccal epithelium. Extracted DNA will be utilised for nanorate sequencing, a newly developed duplex sequencing protocol, which will enable us to accurately detect somatic mutations as well as small insertions and deletions (indels), mutational signatures and underlying processes of DNA damage. Overall, we anticipate the proposed study to improve our understanding of the role of somatic mutations in accelerated ageing phenotypes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007501","title":"Clinical and genetic factors associated with tumor response to neoadjuvant (chemo)radiotherapy, survival and recurrence risk in rectal cancer","description":"Rectal cancer poses challenges in preoperative treatment response, with up to 30% achieving a complete response (CR). Personalized treatment relies on accurate identification of responders at diagnosis. This study aimed to unravel CR determinants, overall survival (OS), and time to recurrence (TTR) using clinical and targeted sequencing data. Analyzing 402 patients undergoing preoperative treatment, tumor stage, size, and treatment emerged as robust response predictors. CR rates were higher in smaller, early-stage, and intensively treated tumors. Targeted sequencing analyzed 216 cases, while 120 patients provided hotspot mutation data. KRAS mutation dramatically reduced CR odds by over 50% (odds ratio [OR]=0.3 in the targeted sequencing and OR=0.4 hotspot cohorts, respectively). In contrast, SMAD4 and SYNE1 mutations were associated with higher CR rates (OR=6.0 and 6.8, respectively). Favorable OS was linked to younger age, CR, and low baseline carcinoembryonic antigen levels. Notably, CR and an APC mutation increased TTR, while a BRAF mutation negatively affected TTR. Beyond tumor burden, SMAD4 and SYNE1 mutations significantly influenced CR. KRAS mutations independently correlated with radiotherapy resistance, and BRAF mutations heightened recurrence risk. Intriguingly, nonresponding tumors with initially small sizes carried a higher risk of recurrence. These findings offer insights into rectal cancer treatment response, guiding personalized therapeutic strategies. By uncovering factors impacting CR, OS, and TTR, this study underscores the importance of tailored approaches for rectal cancer patients. These findings, based on extensive analysis and mutation data, pave the way for personalized interventions, optimizing outcomes in the challenges of rectal cancer preoperative treatment.","abstract":"Rectal cancer poses challenges in preoperative treatment response, with up to 30% achieving a complete response (CR). Personalized treatment relies on accurate identification of responders at diagnosis. This study aimed to unravel CR determinants, overall survival (OS), and time to recurrence (TTR) using clinical and targeted sequencing data. Analyzing 402 patients undergoing preoperative treatment, tumor stage, size, and treatment emerged as robust response predictors. CR rates were higher in smaller, early-stage, and intensively treated tumors. Targeted sequencing analyzed 216 cases, while 120 patients provided hotspot mutation data. KRAS mutation dramatically reduced CR odds by over 50% (odds ratio [OR]=0.3 in the targeted sequencing and OR=0.4 hotspot cohorts, respectively). In contrast, SMAD4 and SYNE1 mutations were associated with higher CR rates (OR=6.0 and 6.8, respectively). Favorable OS was linked to younger age, CR, and low baseline carcinoembryonic antigen levels. Notably, CR and an APC mutation increased TTR, while a BRAF mutation negatively affected TTR. Beyond tumor burden, SMAD4 and SYNE1 mutations significantly influenced CR. KRAS mutations independently correlated with radiotherapy resistance, and BRAF mutations heightened recurrence risk. Intriguingly, nonresponding tumors with initially small sizes carried a higher risk of recurrence. These findings offer insights into rectal cancer treatment response, guiding personalized therapeutic strategies. By uncovering factors impacting CR, OS, and TTR, this study underscores the importance of tailored approaches for rectal cancer patients. These findings, based on extensive analysis and mutation data, pave the way for personalized interventions, optimizing outcomes in the challenges of rectal cancer preoperative treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-17T10:19:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007502","title":"Single-cell RNA-seq data from 5 normal fallopian tube tissue.","description":null,"abstract":"Long interspersed nuclear elements (LINE-1s or L1s) are a group of retrotransposons that can copy themselves within a genome. In our species, it is the most successful transposon in nucleotide content. L1 expression is generally mild in normal human tissues, but the activity has been shown to increase significantly in many tumor types. Only few studies have examined L1 expression at single-cell resolution, thus it is undetermined whether L1 reactivation occurs solely in malignant cells within tumors. One of the cancer types with frequent L1 activity is high-grade serous ovarian carcinoma (HGSOC). Here, we identified locus-specific L1 expression with 3′ single-cell RNA sequencing in pre- and post-chemotherapy HGSOC sample pairs from 11 patients, and in fallopian tube samples from five healthy women. Although L1 expression quantification with the chosen technique was challenging due to the repetitive nature of L1 elements, we found evidence of L1 expression. The expression levels were similar in samples taken before and after neoadjuvant chemotherapy, indicating that L1 transcriptional activity was unaffected by clinical platinum-taxane treatment. Furthermore, we found that L1 activity was negatively associated with the expression of MYC target genes, a finding that supports earlier literature of MYC being an L1 suppressor.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007503","title":"Personalized therapy and penile squamous cell carcinoma:exploring the molecular landscape","description":null,"abstract":"Fifty percent of cases of penile squamous cell carcinoma (PSCC) are associated with HPV infection. PSCC is an aggressive tumour characterized by early locoregional spread and a high risk for disseminated disease. Treatment of localized tumours is associated with significant morbidity while management of advanced disease is often treatment refractory. Our previous research of HPV-driven vulvar carcinoma uncovered several novel mutations, including FGFR-3, which could be used as potential targets in precision medicine therapy. In the current study we will explore the significance of HPV infection in PSCC and analyze the mutational burden of both HPV and non-HPV driven PSCC tumours. Transcriptome sequencing will be performed on archival tissue microdissected from FFPE blocks to identify mutations in oncogenes that could be used as targets in precision medicine treatments. A search of our archived tissues has identified 54 patients diagnosed and treated for PSCC. The size of our patient cohort is ample to complete our initial sequencing studies. We believe that these initial investigations will provide the necessary framework towards developing novel treatment strategies for this often fatal disease.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007504","title":"Personalized therapy and penile squamous cell carcinoma:exploring the molecular landscape","description":null,"abstract":"Fifty percent of cases of penile squamous cell carcinoma (PSCC) are associated with HPV infection. PSCC is an aggressive tumour characterized by early locoregional spread and a high risk for disseminated disease. Treatment of localized tumours is associated with significant morbidity while management of advanced disease is often treatment refractory. Our previous research of HPV-driven vulvar carcinoma uncovered several novel mutations, including FGFR-3, which could be used as potential targets in precision medicine therapy. In the current study we will explore the significance of HPV infection in PSCC and analyze the mutational burden of both HPV and non-HPV driven PSCC tumours. Transcriptome sequencing will be performed on archival tissue microdissected from FFPE blocks to identify mutations in oncogenes that could be used as targets in precision medicine treatments. A search of our archived tissues has identified 54 patients diagnosed and treated for PSCC. The size of our patient cohort is ample to complete our initial sequencing studies. We believe that these initial investigations will provide the necessary framework towards developing novel treatment strategies for this often fatal disease.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007505","title":"SECRETO Oral metagenome study","description":"The main goal of the project is to study the associations between the oral metagenome and young-onset cryptogenic ischemic stroke (CIS). The dataset includes information for n=329 participants who underwent saliva sampling. Participants for the SECRETO Oral study were enrolled between December 2013 and November 2019. Shotgun metagenomic sequencing was performed using the Illumina NovaSeq 6000 platform.","abstract":"The main goal of the project is the study the associations between the oral metagenome and young-onset cryptogenic ischemic stroke (CIS). The dataset contains data for n=329 participants who underwent saliva sampling. Participants for the SECRETO Oral study were recruited between December 2013 and November 2019. Shotgun metagenomic sequencing was performed using the Illumina NovaSeq 6000 platform.","study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-26T12:43:44.954055+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007506","title":"Towards_complete_mutagenesis_of_the_human__foldome_","description":"In this project we quantify the effects on stability and binding of high order mutations in protein cores and interaction interfaces. This allows us to background average mutational effects and epistatic interactions as we build models highly accurate at predicting the effects of high order mutations relevant in the clinics and in protein engineering.","abstract":"Mutational effects and epistatic interactions are highly dependent on the genetic background in which they occur. Therefore, models based on single or double mutational effects measured in the WT background often display limited performance at predicting the effects of higher order mutations, which are important in the clinics (variant classification, pathogen immune evasion, etc.) as well as in protein design and engineering. In this project, we build combinatorial libraries in protein cores and quantify the effect of high order mutations in protein stability, and use this data to train models able to background-average the energetic effects of single mutations as well as pairwise and high order interactions. We use a similar approach to train models with background-averaged energetics in the binding interfaces of protein interacting pairs. As a result we obtain models able to predict the effects of high order mutations in stability and binding affinity-involved hot spots with greater accuracy than thosed based in lower order mutagenesis datasets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007507","title":"Whole genome sequencing of 108 epileptic patients from CENet cohort","description":"Epileptic patients have been sequenced as part of the CENet cohort which is composed of patients with Genetic Generalized Epilepsy (GGE) or Non-Acquired Focal Epilepsy (NAFE) collected in CHUM Research Center in Montreal. Patients were diagnosed by epileptologists. The clinical epilepsy phenotype was classified according to the current classification by the International League against Epilepsy (ILAE).\nLibraries preparation and whole-genome sequencing: gDNA was cleaned up using ZR-96 DNA Clean &amp; ConcentratorTM-5 Kit (Zymo) prior to being quantified using the Quant-iTTM PicoGreen dsDNA Assay Kit (Life Technologies) and its integrity assessed on agarose gels. Libraries were generated using the TruSeq DNA PCR-Free Library Preparation Kit (Illumina) according to the manufacturer’s recommendations. Libraries were quantified using the Quant-iTTM PicoGreen dsDNA Assay Kit (Life Technologies) and the Kapa Illumina GA with Revised Primers-SYBR Fast Universal kit (Kapa Biosystems). Average size fragment was determined using a LabChip GX (PerkinElmer) instrument. The libraries were denatured in 0.05N NaOH and diluted to 8pM using HT1 buffer. The clustering was done on a Illumina cBot and the flowcell was ran on a HiSeq 2500 for 2x125 cycles (paired-end mode) using v4 chemistry and following the manufacturer's instructions. A phiX library was used as a control and mixed with libraries at 0.01 level.\nBioinformatics: The Illumina control software was HCS 2.2.58, the real-time analysis program was RTA v. 1.18.64. Program bcl2fastq v1.8.4 was used to demultiplex samples and generate fastq reads. The filtered reads were aligned to reference Homo_sapiens assembly b37. Each readset was aligned to create a .cram file.","abstract":"Epileptic patients have been sequenced as part of the CENet cohort which is composed of patients with Genetic Generalized Epilepsy (GGE) or Non-Acquired Focal Epilepsy (NAFE) collected in CHUM Research Center in Montreal. Patients were diagnosed by epileptologists. The clinical epilepsy phenotype was classified according to the current classification by the International League against Epilepsy (ILAE).\nLibraries preparation and whole-genome sequencing: gDNA was cleaned up using ZR-96 DNA Clean &amp; ConcentratorTM-5 Kit (Zymo) prior to being quantified using the Quant-iTTM PicoGreen dsDNA Assay Kit (Life Technologies) and its integrity assessed on agarose gels. Libraries were generated using the TruSeq DNA PCR-Free Library Preparation Kit (Illumina) according to the manufacturer’s recommendations. Libraries were quantified using the Quant-iTTM PicoGreen dsDNA Assay Kit (Life Technologies) and the Kapa Illumina GA with Revised Primers-SYBR Fast Universal kit (Kapa Biosystems). Average size fragment was determined using a LabChip GX (PerkinElmer) instrument. The libraries were denatured in 0.05N NaOH and diluted to 8pM using HT1 buffer. The clustering was done on a Illumina cBot and the flowcell was ran on a HiSeq 2500 for 2x125 cycles (paired-end mode) using v4 chemistry and following the manufacturer's instructions. A phiX library was used as a control and mixed with libraries at 0.01 level.\nBioinformatics: The Illumina control software was HCS 2.2.58, the real-time analysis program was RTA v. 1.18.64. Program bcl2fastq v1.8.4 was used to demultiplex samples and generate fastq reads. The filtered reads were aligned to reference Homo_sapiens assembly b37. Each readset was aligned to create a .cram file.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-18T14:40:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007508","title":"ExomeSeq Neoantigen Immunogenicity Landscapes","description":"Immune checkpoint blockade (ICB) therapy is a cornerstone of oncologic treatment for patients with advanced stage non-small cell lung cancer (NSCLC) and other malignancies.  Neoantigen immunoediting drives ICB efficacy, yet the fundamental physiochemical characteristics of neoantigens and how neoantigen immunogenicity shapes treatment response remains poorly understood.  To help address these questions, a prospective clinical trial of NSCLC patients treated with nivolumab was conducted.  We assessed genomic alterations in tumors from 58 patients and performed large-scale neoepitope immunogenicity analyses, before and during treatment (CheckMate153, CA209-153). Tumors were analyzed by whole-exome and transcriptome sequencing. In responding patients, loss of mutation and neoantigen burden early during therapy associated with clinical benefit.  We evaluated the immunogenicity of 1,453 candidate neoantigens and identified 502 neopeptides that bound to MHC I and 196 neopeptides that were immunogenically recognized by T cells in the setting of nivolumab treatment.  These T cell reactive neoantigens were differentially present in clonal populations that underwent distinctive evolutionary trajectories across responders and nonresponders.  Mapping these neoantigens to tumor clonal dynamics and clinical response revealed strong selection against immunogenic neoantigen harboring clones compared to non-immunogenic clones. Using this large collection of neoantigens, we identified position specific amino acid features related to immunogenicity, which we used to develop and validate an immunogenicity score.  Changes in the genomic and neoantigen immunogenicity landscapes were accompanied by temporal changes in the tumor microenvironment.  Nivolumab-induced microenvironmental evolution in NSCLC shared some similarities with that in melanoma, yet critical differences in immunologic programs were apparent from comparative network analysis between tumor types. This study provides unprecedented molecular portraits of the neoantigen landscapes underlying nivolumab’s mechanism of action.","abstract":"Immune checkpoint blockade (ICB) therapy is a cornerstone of oncologic treatment for patients with advanced stage non-small cell lung cancer (NSCLC) and other malignancies.  Neoantigen immunoediting drives ICB efficacy, yet the fundamental physiochemical characteristics of neoantigens and how neoantigen immunogenicity shapes treatment response remains poorly understood.  To help address these questions, a prospective clinical trial of NSCLC patients treated with nivolumab was conducted.  We assessed genomic alterations in tumors from 58 patients and performed large-scale neoepitope immunogenicity analyses, before and during treatment (CheckMate153, CA209-153). Tumors were analyzed by whole-exome and transcriptome sequencing. In responding patients, loss of mutation and neoantigen burden early during therapy associated with clinical benefit.  We evaluated the immunogenicity of 1,453 candidate neoantigens and identified 502 neopeptides that bound to MHC I and 196 neopeptides that were immunogenically recognized by T cells in the setting of nivolumab treatment.  These T cell reactive neoantigens were differentially present in clonal populations that underwent distinctive evolutionary trajectories across responders and nonresponders.  Mapping these neoantigens to tumor clonal dynamics and clinical response revealed strong selection against immunogenic neoantigen harboring clones compared to non-immunogenic clones. Using this large collection of neoantigens, we identified position specific amino acid features related to immunogenicity, which we used to develop and validate an immunogenicity score.  Changes in the genomic and neoantigen immunogenicity landscapes were accompanied by temporal changes in the tumor microenvironment.  Nivolumab-induced microenvironmental evolution in NSCLC shared some similarities with that in melanoma, yet critical differences in immunologic programs were apparent from comparative network analysis between tumor types. This study provides unprecedented molecular portraits of the neoantigen landscapes underlying nivolumab’s mechanism of action.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-18T15:03:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007509","title":"RNASeq Neoantigen Immunogenicity Landscape","description":"Immune checkpoint blockade (ICB) therapy is a cornerstone of oncologic treatment for patients with advanced stage non-small cell lung cancer (NSCLC) and other malignancies.  Neoantigen immunoediting drives ICB efficacy, yet the fundamental physiochemical characteristics of neoantigens and how neoantigen immunogenicity shapes treatment response remains poorly understood.  To help address these questions, a prospective clinical trial of NSCLC patients treated with nivolumab was conducted.  We assessed genomic alterations in tumors from 58 patients and performed large-scale neoepitope immunogenicity analyses, before and during treatment (CheckMate153, CA209-153). Tumors were analyzed by whole-exome and transcriptome sequencing. In responding patients, loss of mutation and neoantigen burden early during therapy associated with clinical benefit.  We evaluated the immunogenicity of 1,453 candidate neoantigens and identified 502 neopeptides that bound to MHC I and 196 neopeptides that were immunogenically recognized by T cells in the setting of nivolumab treatment.  These T cell reactive neoantigens were differentially present in clonal populations that underwent distinctive evolutionary trajectories across responders and nonresponders.  Mapping these neoantigens to tumor clonal dynamics and clinical response revealed strong selection against immunogenic neoantigen harboring clones compared to non-immunogenic clones. Using this large collection of neoantigens, we identified position specific amino acid features related to immunogenicity, which we used to develop and validate an immunogenicity score.  Changes in the genomic and neoantigen immunogenicity landscapes were accompanied by temporal changes in the tumor microenvironment.  Nivolumab-induced microenvironmental evolution in NSCLC shared some similarities with that in melanoma, yet critical differences in immunologic programs were apparent from comparative network analysis between tumor types. This study provides unprecedented molecular portraits of the neoantigen landscapes underlying nivolumab’s mechanism of action.","abstract":"Immune checkpoint blockade (ICB) therapy is a cornerstone of oncologic treatment for patients with advanced stage non-small cell lung cancer (NSCLC) and other malignancies.  Neoantigen immunoediting drives ICB efficacy, yet the fundamental physiochemical characteristics of neoantigens and how neoantigen immunogenicity shapes treatment response remains poorly understood.  To help address these questions, a prospective clinical trial of NSCLC patients treated with nivolumab was conducted.  We assessed genomic alterations in tumors from 58 patients and performed large-scale neoepitope immunogenicity analyses, before and during treatment (CheckMate153, CA209-153). Tumors were analyzed by whole-exome and transcriptome sequencing. In responding patients, loss of mutation and neoantigen burden early during therapy associated with clinical benefit.  We evaluated the immunogenicity of 1,453 candidate neoantigens and identified 502 neopeptides that bound to MHC I and 196 neopeptides that were immunogenically recognized by T cells in the setting of nivolumab treatment.  These T cell reactive neoantigens were differentially present in clonal populations that underwent distinctive evolutionary trajectories across responders and nonresponders.  Mapping these neoantigens to tumor clonal dynamics and clinical response revealed strong selection against immunogenic neoantigen harboring clones compared to non-immunogenic clones. Using this large collection of neoantigens, we identified position specific amino acid features related to immunogenicity, which we used to develop and validate an immunogenicity score.  Changes in the genomic and neoantigen immunogenicity landscapes were accompanied by temporal changes in the tumor microenvironment.  Nivolumab-induced microenvironmental evolution in NSCLC shared some similarities with that in melanoma, yet critical differences in immunologic programs were apparent from comparative network analysis between tumor types. This study provides unprecedented molecular portraits of the neoantigen landscapes underlying nivolumab’s mechanism of action.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-18T15:03:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007510","title":"Immune landscape of oncohistone-mutant gliomas reveals diverse myeloid populations and tumor-promoting behavior","description":"Histone H3-mutant gliomas are deadly brain tumors characterized by a dysregulated epigenome and stalled differentiation. In contrast to the extensive datasets available on tumor cells, limited information exists on their tumor microenvironment (TME), including the immune infiltrate. Here, we characterize the TME of H3.3K27M and G34R/V-mutant gliomas, and multiple H3.3K27M mouse models, using transcriptomic and proteomic, including spatial single-cell approaches. Resolution of immune lineages indicates uniform high-infiltration of H3-mutant gliomas with diverse myeloid populations, high-level expression of immune checkpoints, and scarce lymphoid cells, findings uniformly reproduced in all H3.3K27M models tested. We show these myeloid populations communicate with H3-mutant cells mediating immunosuppression and sustaining tumor formation and maintenance. Dual inhibition of myeloid cells and immune checkpoints showed significant therapeutic benefit in pre-clinical syngeneic models. Our findings provide valuable characterization of the TME of oncohistone-mutant gliomas, and insights into means to modulate the myeloid infiltrate for the benefit of patients.","abstract":"Histone H3-mutant gliomas are deadly brain tumors characterized by a dysregulated epigenome and stalled differentiation. In contrast to the extensive datasets available on tumor cells, limited information exists on their tumor microenvironment (TME), including the immune infiltrate. Here, we characterize the TME of H3.3K27M and G34R/V-mutant gliomas, and multiple H3.3K27M mouse models, using transcriptomic and proteomic, including spatial single-cell approaches. Resolution of immune lineages indicates uniform high-infiltration of H3-mutant gliomas with diverse myeloid populations, high-level expression of immune checkpoints, and scarce lymphoid cells, findings uniformly reproduced in all H3.3K27M models tested. We show these myeloid populations communicate with H3-mutant cells mediating immunosuppression and sustaining tumor formation and maintenance. Dual inhibition of myeloid cells and immune checkpoints showed significant therapeutic benefit in pre-clinical syngeneic models. Our findings provide valuable characterization of the TME of oncohistone-mutant gliomas, and insights into means to modulate the myeloid infiltrate for the benefit of patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-18T21:26:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007511","title":"Shared and distinct features of immune checkpoint therapy-induced myocarditis and myositis","description":"Immune checkpoint therapies (ICTs) can induce life-threatening immune-related adverse events including myocarditis and myositis, which are rare and often concurrent. The molecular pathways and immune subsets underlying these toxicities remain poorly understood.","abstract":"Immune checkpoint therapies (ICTs) can induce life-threatening immune-related adverse events including myocarditis and myositis, which are rare and often concurrent. The molecular pathways and immune subsets underlying these toxicities remain poorly understood.","study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-22T10:32:41.904842+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007512","title":"Single cell transcriptomic landscape of pediatric B-cell acute lymphoblastic leukemia: dissection of transcriptional heterogeneity and B-cell developmental state","description":"Introduction: Genomic analyses of bulk ALL samples have improved our understanding of the genetic basis and risk stratification of B-ALL, but do not directly examine intratumor heterogeneity or enable inference of leukemia developmental state and cell of origin.    Methods: We profiled 89 B-ALL samples by single-cell RNA-seq (scRNA-seq) (10X Genomics 5’v2) and compared them to a scRNA-seq reference map of normal human B-cell development. Results: Analysis of heterogeneity of inferred DNA copy number alterations at single cell level showed that aneuploid ALL with near haploidy and hyperdiploid harbor chromosomal losses or gains in all blasts, consistent with early, synchronous origin rather than sequential accumulation. Intra-sample heterogeneity was driven by five gene expression signatures: cell cycle, metabolism, differentiation, inflammation, refining leukemic subtyping. An atlas of B cell development was established to map B-ALL samples to specific developmental states. Hyperdiploid samples resembled pro-B cells, while MEF2D-r and TCF3::PBX1 showed high pre-B abundance. Patients with high early lymphoid abundance had poorer outcomes. Conclusions: Understanding variation in transcriptional programs and developmental states of B-ALL blasts by sc transcriptome refines existing clinical and genomic classifications and provides novel prognostic markers.","abstract":"Introduction: Genomic analyses of bulk ALL samples have improved our understanding of the genetic basis and risk stratification of B-ALL, but do not directly examine intratumor heterogeneity or enable inference of leukemia developmental state and cell of origin.    Methods: We profiled 89 B-ALL samples by single-cell RNA-seq (scRNA-seq) (10X Genomics 5’v2) and compared them to a scRNA-seq reference map of normal human B-cell development. Results: Analysis of heterogeneity of inferred DNA copy number alterations at single cell level showed that aneuploid ALL with near haploidy and hyperdiploid harbor chromosomal losses or gains in all blasts, consistent with early, synchronous origin rather than sequential accumulation. Intra-sample heterogeneity was driven by five gene expression signatures: cell cycle, metabolism, differentiation, inflammation, refining leukemic subtyping. An atlas of B cell development was established to map B-ALL samples to specific developmental states. Hyperdiploid samples resembled pro-B cells, while MEF2D-r and TCF3::PBX1 showed high pre-B abundance. Patients with high early lymphoid abundance had poorer outcomes. Conclusions: Understanding variation in transcriptional programs and developmental states of B-ALL blasts by sc transcriptome refines existing clinical and genomic classifications and provides novel prognostic markers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-21T21:03:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007513","title":"Systematic analysis of paralogous regions in 41,755 exomes uncovers clinically relevant variation","description":"As part of the study \"Systematic analysis of paralogous regions in 41,755 exomes uncovers clinically relevant variation\" we wanted to identiffy the SNVs that are located in STRC and which ones in STRCP1. For this we applied targeted long-read sequencing.","abstract":"As part of the study \"Systematic analysis of paralogous regions in 41,755 exomes uncovers clinically relevant variation\" we wanted to identiffy the SNVs that are located in STRC and which ones in STRCP1. For this we applied targeted long-read sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-22T07:53:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007514","title":"Low-coverage whole-genome sequencing of cancer and healthy plasma circulating DNA","description":null,"abstract":"Plasma samples from patients with melanoma (stage II/III/IV) and breast cancer (stage IV) as well as healthy individuals were subjected to whole-genome sequencing to generate low-coverage (&lt;10x) sequencing datasets.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007515","title":"AfricanNeo ModernDNA Study","description":null,"abstract":"With the largest genomic dataset to date of Bantu-speaking populations, including newly generated data of modern-day and ancient DNA from previously unsampled regions in Africa, we shed fresh light on the expansion of peoples speaking Bantu languages that started ~4000 years ago in western Africa. We have genotyped 1,763 participants, including 1,487 Bantu speakers from 143 populations across 14 African countries. Our comprehensive genetic analysis of the expansion of people speaking Bantu languages reveals a complex history of serial founder events, variable levels of contact with local groups, and spread-over-spread events.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007516","title":"RAGE engagement by SARS-CoV-2 enables monocyte infection and underlies COVID-19 severity","description":null,"abstract":"The spread of SARS-CoV-2 has fuelled the COVID-19 pandemic with its enduring medical and socioeconomic challenges due to subsequent waves and long-term consequences of great concern. Here we chart the molecular basis of COVID-19 pathogenesis, by analysing patients’ immune response at single-cell resolution across disease course and severity. This approach confirms cell subpopulation-specific dysregulation in COVID-19 across disease course and severity and identifies a severity-associated activation of the receptor for advanced glycation endproduct (RAGE) pathway in monocytes.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007517","title":"AfricanNeo Genotyped Dataset","description":"With the largest genomic dataset to date of Bantu-speaking populations, including newly generated data of modern-day and ancient DNA from previously unsampled regions in Africa, we shed fresh light on the expansion of peoples speaking Bantu languages that started ~4000 years ago in western Africa. We have genotyped 1,763 participants, including 1,487 Bantu speakers from 143 populations across 14 African countries, and generated whole-genome sequences from 12 Late Iron Age individuals. Our comprehensive genetic analysis of the expansion of people speaking Bantu languages reveals a complex history of serial founder events, variable levels of contact with local groups, and spread-over-spread events.","abstract":"With the largest genomic dataset to date of Bantu-speaking populations, including newly generated data of modern-day and ancient DNA from previously unsampled regions in Africa, we shed fresh light on the expansion of peoples speaking Bantu languages that started ~4000 years ago in western Africa. We have genotyped 1,763 participants, including 1,487 Bantu speakers from 143 populations across 14 African countries, and generated whole-genome sequences from 12 Late Iron Age individuals. Our comprehensive genetic analysis of the expansion of people speaking Bantu languages reveals a complex history of serial founder events, variable levels of contact with local groups, and spread-over-spread events.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007518","title":"scRNA-seq, scTCR-seq and bulk RNAseq on HNSCC patients treated with ICB","description":null,"abstract":"We performed single cell RNA and TCR sequencing (10x Genomics) on immune infiltrates (CD45+ cells) from 18 HNSCC patients enrolled in the IMCISION trial (Vos et al. 2021). Viable immune cells were isolated from pre-treatment and on-treatment primary tumor biopsies of 10 patients responding (1 partial pathological response and 9 major pathological responses) and 7 patients non-responding to anti-PD-1 and anti-CTLA4 combination immunotherapy. One patient treated with anti-PD-1 monotherapy (1 major pathological response) was included in the dataset.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007519","title":"AfricanNeo aDNA Study","description":"With the largest genomic dataset to date of Bantu-speaking populations, including newly generated data of modern-day and ancient DNA from previously unsampled regions in Africa, we shed fresh light on the expansion of peoples speaking Bantu languages that started ~4000 years ago in western Africa. We have generated whole-genome sequences from 12 Late Iron Age individuals. Our comprehensive genetic analysis of the expansion of people speaking Bantu languages reveals a complex history of serial founder events, variable levels of contact with local groups, and spread-over-spread events.","abstract":"With the largest genomic dataset to date of Bantu-speaking populations, including newly generated data of modern-day and ancient DNA from previously unsampled regions in Africa, we shed fresh light on the expansion of peoples speaking Bantu languages that started ~4000 years ago in western Africa. We have generated whole-genome sequences from 12 Late Iron Age individuals. Our comprehensive genetic analysis of the expansion of people speaking Bantu languages reveals a complex history of serial founder events, variable levels of contact with local groups, and spread-over-spread events.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-22T16:38:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007520","title":"Genomic profiling of IBC","description":"We collected matched pretreatment blood and tumor samples from 19 patients with primary TN-IBC enrolled in a phase II clinical trial (NCT02876107). Patients were treated with neoadjuvant chemotherapy (NAC) or the anti-EGFR antibody panitumumab (PmAb) plus NAC (PmAb/NAC). We conducted whole-exome sequencing, RNA sequencing, and CIBERSORT analyses for these TN-IBC samples and compare the genetic and molecular profiles with similarly analyzed stage III TN-non-IBC patient samples. We also compared the genetic and molecular characteristics of TN-IBC in patients who had a pathologic complete response (pCR) to NAC or PmAb/NAC treatment, a suitable surrogate endpoint for IBC, with those who did not have pCR (non-pCR).","abstract":"We collected matched pretreatment blood and tumor samples from 19 patients with primary TN-IBC enrolled in a phase II clinical trial (NCT02876107). Patients were treated with neoadjuvant chemotherapy (NAC) or the anti-EGFR antibody panitumumab (PmAb) plus NAC (PmAb/NAC). We conducted whole-exome sequencing, RNA sequencing, and CIBERSORT analyses for these TN-IBC samples and compare the genetic and molecular profiles with similarly analyzed stage III TN-non-IBC patient samples. We also compared the genetic and molecular characteristics of TN-IBC in patients who had a pathologic complete response (pCR) to NAC or PmAb/NAC treatment, a suitable surrogate endpoint for IBC, with those who did not have pCR (non-pCR).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-22T17:56:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007521","title":"FFPE WGS for optimizing mutation signature extraction from archival HGSC samples","description":"HGSC cases were selected for which matched fresh frozen and FFPE samples were available from the same tissue specimens.  Fresh frozen, FFPE and normal blood were subject to WGS for the purpose of assessing the possibility of using FFPE WGS in place of fresh frozen for somatic mutation calling","abstract":"HGSC cases were selected for which matched fresh frozen and FFPE samples were available from the same tissue specimens.  Fresh frozen, FFPE and normal blood were subject to WGS for the purpose of assessing the possibility of using FFPE WGS in place of fresh frozen for somatic mutation calling","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-22T22:48:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007522","title":"CITE-seq of patient-matched decidua parietalis and decidua basalis","description":null,"abstract":"The objective of this study was to examine the impact of placentation during the first trimester of human pregnancy on the uterine mucosa and associated immune cells. To differentiate between the systemic effects commonly associated with pregnancy and the local effects resulting from placental invasion and cell interactions, the decidua parietalis was used as an in-patient control. Unlike the decidua basalis, which is infiltrated by placental cells, the decidua parietalis is a part of the maternal uterine mucosa that does not come into contact with the placenta. This distinction provided a valuable perspective for isolating and understanding the specific effects of placentation.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007523","title":"Molecular Profile of Meningiomas in Brazilian Patients","description":null,"abstract":"Meningiomas are the most common primary intracranial tumors in adults. Although the current World Health Organization (WHO) classification of meningiomas only considers histopathological features, the latest integrated molecular characterization of these tumors is providing a better understanding of their biology and allowing the identification of prognostic subgroups and therapeutic biomarkers. We performed whole exome sequencing using paired fresh frozen tissue and blood from 27 meningiomas. We identified mutational signatures, somatic variants and copy number alterations (CNAs) and associated with patients' clinicopathological features. This comprehensive genomic study of Brazilian meningiomas showed that the patients exhibited a similar profile that reported in other populations. We also identified some recurrent variants potentially associated with targeted therapies.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007524","title":"UKF_Paediatric_Tumours_Behjati_WellcomeCore_RNA_Managed_Access","description":"Children born with DS have a substantially higher risk of developing childhood leukaemia. Approximately 10% are diagnosed with a preleukemic condition at birth; transient abnormal myelopoiesis (TAM). Of these, 20% - 30% of cases may progress to myeloid leukaemia associated with DS (MLDS) by the age of five. We are interested in directly characterizing the transcriptional changes underlying this stepwise development of TAM and MLDS.","abstract":"Children born with DS have a substantially higher risk of developing childhood leukaemia. Approximately 10% are diagnosed with a preleukemic condition at birth; transient abnormal myelopoiesis (TAM). Of these, 20% - 30% of cases may progress to myeloid leukaemia associated with DS (MLDS) by the age of five. We are interested in directly characterizing the transcriptional changes underlying this stepwise development of TAM and MLDS.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-23T15:20:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007525","title":"Integrative genomic analyses of European intrahepatic cholangiocarcinoma: new ROS1 fusion gene and PBX1 as prognostic marker","description":null,"abstract":"Cholangiocarcinoma (CCA) is a fatal cancer of the bile duct with a poor prognosis due to limited therapeutic options. Intrahepatic CCA (iCCA) is particularly rising worldwide and its molecular basis is just emerging. Environmental factors contribute to regional differences in mutation spectrum with European iCCA patients being underrepresented in systematic genomic and transcriptomic studies. Here we describe an integrated whole exome sequencing and transcriptomic study of 37 iCCAs of German patients. We observed as most frequently mutated genes ARID1A (14%) and IDH1, BAP1, TP53, KRAS, and ATM each in 8% of patients. We identified FGFR2::BICC1 fusions in two tumors and FGFR2::KCTD1 and TMEM106B::ROS1 as new fusions and therapeutic targets for iCCA. Using a data integration framework, we identified PBX1 as a new central regulatory gene for iCCA. We performed an extended screen by targeted sequencing of additional 40 CCAs. In the joint analysis, IDH1 (13%), BAP1 (10%), TP53 (9%), KRAS (7%), ARID1A (7%), NF1 (5%), and ATM (5%) were the most frequently mutated genes and we found PBX1 to show copy gain in 20% of tumors. Considering other studies, amplifications of PBX1 tend to occur in European iCCAs in contrast to liver fluke-associated Asian iCCAs. Analyzing an additional European cohort of iCCA, we found PBX1 protein expression to be a marker for poor prognosis. Overall, our findings add insight into key molecular alterations of iCCA, reveal new targetable fusion genes, and suggest PBX1 as a new modulator of the disease.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-24T10:20:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007526","title":"WXS Normal Samples Javelin head and neck 100","description":null,"abstract":"Immune checkpoint blockade (ICB) has improved patient outcomes in multiple cancers, including head and neck squamous cell carcinomas (HNSCC), yet many patients do not benefit. Combination therapies integrating immunotherapy are benefitting patients but the drivers of efficacy are not understood.  Here we report genomic, microenvironmental, and tumor microbiome correlates of efficacy to avelumab combined with standard of care chemoradiotherapy (CRT) in the phase 3 randomized, double-blinded, placebo-controlled study in patients with locally advanced squamous cell carcinoma of the head and neck JAVELIN Head and Neck 100 (NCT02952586).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-24T21:44:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007527","title":"Evolutionary trajectories of IDH-mutant astrocytoma identify molecular grading markers related to cell cycling","description":"To study the evolutionary processes that drive malignant transformation in IDH-mutant astrocytomas, we performed multi-omics on a large cohort of matched initial and recurrent tumor samples. We find that genome-wide DNA-methylation levels decreased over time, mainly in patients with high-grade recurrences. DNA-demethylation was lifted from specific loci associated with DNA replication, and was associated with upregulation of cell cycling associated genes. Upregulation of cell cycling genes occurred predominantly in proliferating tumor cells, and was associated with tumor grade. Temporal DNA-demethylation and upregulation of cell cycling were hardly affected by chemo- and/or radiotherapy, indicating treatment does not affect the course of disease.\nFurther, we defined a DNA-methylation based signature associated with tumor grade and poor prognostic genetic events, with a prognostic power stronger than CDKN2A/B deletion. We validated its prognostic power on primary tumor samples of patients included in the CATNON randomized phase 3 clinical trial. Therefore this model can serve as a molecular grading marker for IDH-mutant astrocytomas.","abstract":"To study the evolutionary processes that drive malignant transformation in IDH-mutant astrocytomas, we performed multi-omics on a large cohort of matched initial and recurrent tumor samples. We find that genome-wide DNA-methylation levels decreased over time, mainly in patients with high-grade recurrences. DNA-demethylation was lifted from specific loci associated with DNA replication, and was associated with upregulation of cell cycling associated genes. Upregulation of cell cycling genes occurred predominantly in proliferating tumor cells, and was associated with tumor grade. Temporal DNA-demethylation and upregulation of cell cycling were hardly affected by chemo- and/or radiotherapy, indicating treatment does not affect the course of disease.\nFurther, we defined a DNA-methylation based signature associated with tumor grade and poor prognostic genetic events, with a prognostic power stronger than CDKN2A/B deletion. We validated its prognostic power on primary tumor samples of patients included in the CATNON randomized phase 3 clinical trial. Therefore this model can serve as a molecular grading marker for IDH-mutant astrocytomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-06-25T17:25:49.158084+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007528","title":"RNA sequencing of control OM cells exposed to traffic-related air pollutants","description":null,"abstract":"Total RNA sequencing of olfactory mucosa (OM) cells derived from cognitively healthy individuals exposed to traffic-related ultrafine particles (UFPs) for 24h and 72h in submerged cultures. The UFPs used for exposures were: A0, A20 and Euro6. Exposures were compared to the corresponding blank samples.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-28T10:20:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007529","title":"RAGE engagement by SARS-CoV-2 enables monocyte infection and underlies COVID-19 severity","description":null,"abstract":"The spread of SARS-CoV-2 has fuelled the COVID-19 pandemic with its enduring medical and socioeconomic challenges due to subsequent waves and long-term consequences of great concern. Here we chart the molecular basis of COVID-19 pathogenesis, by analysing patients’ immune response at single-cell resolution across disease course and severity. This approach confirms cell subpopulation-specific dysregulation in COVID-19 across disease course and severity and identifies a severity-associated activation of the receptor for advanced glycation endproduct (RAGE) pathway in monocytes.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-28T11:52:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007530","title":"Mevalonate Metabolism fuels pro-inflammatory function of Vd2 T cells","description":null,"abstract":"Mevalonate metabolism is essential for proper functioning of eukaryotic cells. Widely prescribed drugs, like statins and bisphosphonates, inhibit specific enzymes in the mevalonate pathway and modulate immune responses. Intermediate metabolites of the pathway activate innate-like Vd2 T cells, while bisphosphonates effectively expand these cells for potential therapeutic use. Yet, the role of the mevalonate metabolism in Vd2 T cells is poorly defined. We show that in vitro and in vivo inhibition of the mevalonate metabolism results in compromised cytokine production and cytotoxic activity of Vd2 T cells. Impaired Vd2 T cell function is accompanied by global transcriptome changes. Protein prenylation and kinome analysis unraveled dysregulated signaling pathways as the leading cause of the reduced effector function of Vd2 T cells upon mevalonate pathway inhibition. Our findings reveal the importance of mevalonate metabolism for the proper functioning of Vd2 T cells and provides important considerations for improving their therapeutic use.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-28T14:29:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007531","title":"Aberrant EZHIP Expression Drives Tumorigenesis in Osteosarcoma","description":null,"abstract":"Osteosarcomas (OS) are aggressive bone tumors characterized by extensive structural variation, and rare recurrent oncogenic driver mutations. Here, we identify ectopic expression of the oncohistone-mimic EZHIP in more than 20% of patients, in two independent OS cohorts. Through gain- and loss-of-function experiments, we provide evidence that EZHIP expression is oncogenic, increasing the aggressive features of OS in vitro and in vivo. EZHIP-mediated epigenetic rewiring promotes reactivation of developmental transcriptional programs and stalled differentiation of mesenchymal progenitors, which are skewed towards smooth muscle commitment at the expense of other lineages. Our findings of EZHIP expression as a prevalent driver in OS provide new insights into pathogenic pathways and therapeutic alternatives for this debilitating cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-28T18:54:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007532","title":"Peripheral blood DNA methylation of Crohn's disease patients starting treatment with adalimumab, vedolizumab or ustekinumab","description":"In the current study we performed a longitudinal case-control study comparing the peripheral blood DNA methylome of Crohn's disease (CD) patients that were classified as responders and non-responders to adalimumab, vedolizumab, and ustekinumab. Patients with active CD were prospectively recruited and followed up for around 27 weeks into treatment during which response assessment took place. Response was defined as a strict combination of endoscopic- (≥50% reduction in SES-CD score) combined with either corticosteroid-free clinical- (≥3 point drop87 in HBI or HBI ≤4 and no systemic steroids) and/or biochemical response (C-reactive protein (CRP) and fecal calprotectin reduction ≥50% or ≤5 g/mL and fecal calprotectin ≤250 µg/g).","abstract":"In the current study we performed a longitudinal case-control study comparing the peripheral blood DNA methylome of Crohn's disease (CD) patients that were classified as responders and non-responders to adalimumab, vedolizumab, and ustekinumab. Patients with active CD were prospectively recruited and followed up for around 27 weeks into treatment during which response assessment took place. Response was defined as a strict combination of endoscopic- (≥50% reduction in SES-CD score) combined with either corticosteroid-free clinical- (≥3 point drop87 in HBI or HBI ≤4 and no systemic steroids) and/or biochemical response (C-reactive protein (CRP) and fecal calprotectin reduction ≥50% or ≤5 g/mL and fecal calprotectin ≤250 µg/g).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-28T21:37:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007533","title":"Convergent evolution of extrachromosomal DNA drives therapy resistance in DNA repair-deficient mCRPC","description":null,"abstract":"Targeted cancer therapies can prolong the lives of men with metastatic castration resistant prostate cancer (mCRPC). However, these treatments also selectively favor the growth of tumor cells that harbor therapy resistance, and mCRPC is currently lethal. It has been challenging to study factors influencing how therapy resistance develops in this setting because few autopsy studies of have been performed in the settings of DNA-repair deficient mCRPC. Here, we assessed how resistance to targeted cancer therapies evolved in an autopsy cohort of 53 mCRPC tumors from six such men. This dataset includes paired FASTQ files from targeted sequencing, exome sequencing, and RNA-seq conducted on these biopsies.\nPatients were treated with multiple lines of therapy with samples obtained at the time of rapid autopsy following the CASCADE protocol. Multiple biopsies were obtained from each patient under guidance of pathology. DNA were analyzed by high-depth whole genome, exome, and targeted sequencing with a NovaSeq 6000. RNA were analyzed using a Nugen amplification protocol as described in Quigley Cell 2018.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007534","title":"RNA sequencing on intestinal biopsies from inflammatory bowel disease patients treated with vehicle control, MEK inhibitor, or infliximab","description":"By investigating an intergenic haplotype on chr21q22, independently linked to inflammatory bowel disease (IBD), ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis, we discover that the causal gene, ETS2, is a master regulator of inflammatory responses in human macrophages and delineate how the risk haplotype increases ETS2 expression. Using a database of cellular signatures, we identified drugs that could modulate this pathway. To validate the anti-inflammatory activity of one class of small molecules ex vivo, we obtained biopsies from patients with active IBD and cultured these biopsies with a selective, non-ATP competitive MEK inhibitor (PD-0325901), infliximab (positive control), or DMSO (vehicle control) for 18 hours, then performed RNA sequencing.","abstract":"By investigating an intergenic haplotype on chr21q22, independently linked to inflammatory bowel disease (IBD), ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis, we discover that the causal gene, ETS2, is a master regulator of inflammatory responses in human macrophages and delineate how the risk haplotype increases ETS2 expression. Using a database of cellular signatures, we identified drugs that could modulate this pathway. To validate the anti-inflammatory activity of one class of small molecules ex vivo, we obtained biopsies from patients with active IBD and cultured these biopsies with a selective, non-ATP competitive MEK inhibitor (PD-0325901), infliximab (positive control), or DMSO (vehicle control) for 18 hours, then performed RNA sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-29T12:10:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007535","title":"Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO)","description":null,"abstract":"154 patients received lapatinib, 149 trastuzumab, and 152 the combination. pCR rate was significantly higher in the group given lapatinib and trastuzumab (78 of 152 patients [51·3%; 95% CI 43·1-59·5]) than in the group given trastuzumab alone (44 of 149 patients [29·5%; 22·4-37·5]; difference 21·1%, 9·1-34·2, p=0·0001). We recorded no significant difference in pCR between the lapatinib (38 of 154 patients [24·7%, 18·1-32·3]) and the trastuzumab (difference -4·8%, -17·6 to 8·2, p=0·34) groups. No major cardiac dysfunctions occurred. Frequency of grade 3 diarrhoea was higher with lapatinib (36 patients [23·4%]) and lapatinib plus trastuzumab (32 [21·1%]) than with trastuzumab (three [2·0%]). Similarly, grade 3 liver-enzyme alterations were more frequent with lapatinib (27 [17·5%]) and lapatinib plus trastuzumab (15 [9·9%]) than with trastuzumab (11 [7·4%]).","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007536","title":"GOSH_Paediatric_Tumour_23P108_WSSS_WGS_Managed_Access","description":"We have a case of two siblings (twins) who were born with nodular blue rashes over their body. The first twin had a large periorbital subcutaneous mass which was diagnosed as infantile undifferentiated sarcoma. This baby was too systematically unwell for chemotherapy and died at 12 days of age. The second sibling received two cycles of emergency chemotherapy however died due to disease progression and secondary haemorrhage at 2 months of age. Post-mortem normal and tumour samples have been taken. In addition to placental tissue and parental germline DNA, the goal will be to investigate intra-uterine transfer of sarcoma and the phylogenetic relationship of tumours in both twins.","abstract":"We have a case of two siblings (twins) who were born with nodular blue rashes over their body. The first twin had a large periorbital subcutaneous mass which was diagnosed as infantile undifferentiated sarcoma. This baby was too systematically unwell for chemotherapy and died at 12 days of age. The second sibling received two cycles of emergency chemotherapy however died due to disease progression and secondary haemorrhage at 2 months of age. Post-mortem normal and tumour samples have been taken. In addition to placental tissue and parental germline DNA, the goal will be to investigate intra-uterine transfer of sarcoma and the phylogenetic relationship of tumours in both twins.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-29T14:38:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007537","title":"Addenbrookes_Paediatric_Tumour_G17228_WSSS_WGS_Managed_Access","description":"This child was diagnosed and succumbed to a stage 4S Neuroblastoma, these usually have an extremely good prognosis however in this case, uniquely presented with aggressive disease. This presents us with the opportunity to establish if the stage 4S disease was metastatic or had synchronous primary tumours, as well as analysis regarding the genetic relationship between normal and tumour.","abstract":"This child was diagnosed and succumbed to a stage 4S Neuroblastoma, these usually have an extremely good prognosis however in this case, uniquely presented with aggressive disease. This presents us with the opportunity to establish if the stage 4S disease was metastatic or had synchronous primary tumours, as well as analysis regarding the genetic relationship between normal and tumour.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007538","title":"The effects of inhaled corticosteroids on healthy airways","description":null,"abstract":"Rationale: The effects of inhaled corticosteroids (ICS) on healthy airways are poorly defined. \nObjectives:  To delineate the effects of ICS on gene expression in healthy airways, without confounding caused by changes in disease-related genes and disease-related alterations in ICS-responsiveness. \nMethods: Randomised open-label bronchoscopy study of high dose ICS therapy in 30 healthy adult volunteers randomised 2:1 to i) fluticasone propionate 500 mcg bd or ii) no treatment, for 4 weeks. Laboratory staff were blinded to allocation. Biopsies and brushings were analysed by immunohistochemistry, bulk RNA sequencing, DNA methylation array and metagenomics.\nMeasurements and main results: ICS induced small between-group differences in blood and lamina propria eosinophils numbers, but not in other immunopathological features, blood neutrophils, FeNO, FEV1, microbiome or DNA methylation. ICS treatment upregulated 72 genes in brushings and 53 genes in biopsies, and downregulated 82 genes in brushings and 416 genes in biopsies. The most downregulated genes in both tissues were canonical markers of type-2 inflammation (FCER1A, CPA3, IL33, CLEC10A, SERPINB10 and CCR5), T cell-mediated adaptive immunity (TARP, TRBC1, TRBC2, PTPN22, TRAC, CD2, CD8A, HLA-DQB2, CD96, PTPN7), B cell immunity (CD20, immunoglobulin heavy and light chains), and innate immunity, including CD48, Hobit, RANTES, Langerin and GFI1. An IL-17-dependent gene signature was not upregulated by ICS.\nConclusions: In healthy airways, 4-week ICS exposure reduces gene expression related to both innate and adaptive immunity, and reduces markers of type-2 inflammation. This implies that homeostasis in health involves tonic type-2 signalling in the airway mucosa, which is exquisitely sensitive to ICS.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-07-22T17:17:01.788475+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007539","title":"CTD-ILD_BALF_and_blood_scRNA-seq_data","description":null,"abstract":"we analyzed immune cells in BALF and blood samples from patients with newly developed CTD-ILD using single-cell RNA sequencing. We aimed to clarify the pathogenesis of SS-ILD and investigate its characteristics in terms of the distribution and gene expression in BALF and blood immune cells in detail compared to other diseases.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-30T08:29:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007540","title":"GLASS-NL DNA-methylation Study","description":null,"abstract":"Low-grade IDH-mutant glioma are notoriously unpredictable and knowledge on the evolutionary trajectories is limited. The GLASS-NL consortium performed methylome profiling on paired initial and recurrent IDH-mutant astrocytoma tumours to elucidate the temporal changes in DNA-methylation. Whole-exome sequencing data and RNA-sequencing data from these samples are submitted separately.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007541","title":"CASM_Epithelioids_Adult_Martincorena_RNA","description":"Single-cell sequencing of epithelioid cultures","abstract":"Epithelioids are a new type of 3D primary culture that recapitulate the structure, organisation and cell type specialisation of epithelia, and can grow stably in vitro without the need of passages for many months. We have been able to generate epithelioid cultures from a variety of human and mouse tissues, including skin, oesophagus, oral, trachea, bladder and endometrium, among others. The goal of this study is to use single-cell RNA sequencing to study how well these cultures recapitulate the cell type and cell state composition of a range of epithelial tissues.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007542","title":"Massively parallel functional dissection of schizophrenia associated non-coding genetic variants","description":"Schizophrenia (SCZ) is a severe mental disorder affecting 1% of the world population.  SCZ is characterized by an underlying genetic architecture that is highly polygenic. Genome wide association studies have identified thousands of genetic variants that are statistically linked to the disease. However, the translation of these associations into insights on the pathomechanisms has been challenging because the causal genetic variants, their molecular function, and their target genes remain largely unknown. To address these questions, we combined induced pluripotent stem cell technology with a massively parallel variant annotation pipeline (MVAP) to functionally characterize 35,000 SCZ associated non-coding genetic variants.  This approach identified a set of 620 (1.7%) single nucleotide polymorphisms as functional on the molecular level in a highly cell type and condition specific fashion. Subsequent multi-modal integration of epigenomic data combined with CRISPR screening in human neurons enabled us to systematically translate SCZ variant associations into target genes, biological processes, and ultimately alterations of neuronal physiology. These results provide a new high-resolution map of functional variant-gene combinations and offer comprehensive biological insights into the developmental context and stimulus dependent molecular processes modulated by SCZ genetic variation beyond statistical association.","abstract":"Schizophrenia (SCZ) is a severe mental disorder affecting 1% of the world population.  SCZ is characterized by an underlying genetic architecture that is highly polygenic. Genome wide association studies have identified thousands of genetic variants that are statistically linked to the disease. However, the translation of these associations into insights on the pathomechanisms has been challenging because the causal genetic variants, their molecular function, and their target genes remain largely unknown. To address these questions, we combined induced pluripotent stem cell technology with a massively parallel variant annotation pipeline (MVAP) to functionally characterize 35,000 SCZ associated non-coding genetic variants.  This approach identified a set of 620 (1.7%) single nucleotide polymorphisms as functional on the molecular level in a highly cell type and condition specific fashion. Subsequent multi-modal integration of epigenomic data combined with CRISPR screening in human neurons enabled us to systematically translate SCZ variant associations into target genes, biological processes, and ultimately alterations of neuronal physiology. These results provide a new high-resolution map of functional variant-gene combinations and offer comprehensive biological insights into the developmental context and stimulus dependent molecular processes modulated by SCZ genetic variation beyond statistical association.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-30T10:53:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007543","title":"Spatial_Transcriptomics_Visium_Pilot_Study_Of_Terminal_Ileum","description":"We will perform spatial transcriptomics (ST) of terminal ileum to inform on epithelial cell markers of the crypt-villus axis. This will aid our TI cell atlas study (manuscript in progress) and inform on whether our biopsies are suitable for ST as we are banking biopsies for future validation by genotype studies.\nCurrently, these studies are not available for human tissue, only mouse spatial genomics studies have been performed using laser capture-RNAseq. These experiments have identified different functions of enterocytes located at the top and bottom of villi in mice.","abstract":"We will perform spatial transcriptomics (ST) of terminal ileum to inform on epithelial cell markers of the crypt-villus axis. This will aid our TI cell atlas study (manuscript in progress) and inform on whether our biopsies are suitable for ST as we are banking biopsies for future validation by genotype studies.\nThe aims of this study are : \n\n1: Explore transcriptomics of cell at crypt-villus axis location to support human TI atlas. Visium Cyassist resolution is approximate 1-10 cell resolution on average /spot.\n2: To inform on the effects of dissociation cell protocol followed to perform scRNAseq experiments. Note that biopsies are fixed and embedded in wax for long term storage vs. ice digest for scRNAseq.\n3: Protocol development to check our processing and storage is adequate, and we are ready to rapidly validate genotype-specific studies i.e. single cell eQTL mapping validation","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007544","title":"TSG-6+ Cancer-Associated Fibroblasts Modulate Myeloid Cell Responses and Impair Anti-Tumor Response to Immune Checkpoint Therapy","description":null,"abstract":"Resistance to immune checkpoint therapy (ICT) presents a growing clinical challenge. The tumor microenvironment (TME) and its components, namely tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), play a pivotal role in ICT resistance; however, the underlying mechanisms remain under investigation. In this study, we identified expression of the protein TNF-Stimulated Factor 6 (TSG-6) in ICT-resistant pancreatic tumors, compared to ICT-sensitive melanoma tumors, both in mouse and human. TSG-6 was expressed by CAFs within the TME, where suppressive macrophages expressing Arg1, Mafb, and Mrc1, along with TSG-6 ligand Cd44, predominated. TSG-6 induced expression of these genes in bone-marrow derived macrophages, indicating a direct role in regulating immunosuppressive myeloid phenotypes. Importantly, TSG-6 inhibition in combination with ICT improved therapy response and survival in tumor-bearing mice by reducing macrophage abundance and increasing CD8 T cells. Overall, our findings propose TSG-6 as a novel therapeutic target to enhance ICT responses in non-responsive tumors.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007545","title":"Machine learning guided signal enrichment for ultrasensitive plasma tumor burden monitoring","description":"In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole genome sequencing (WGS). We now introduce MRD-EDGE, a composite machine learning-guided WGS ctDNA single nucleotide variant (SNV) and copy number variant (CNV) detection platform designed to increase signal enrichment. MRD-EDGESNV uses deep learning and a ctDNA-specific feature space to increase SNV signal-to-noise enrichment in WGS by 300X compared to previous WGS error suppression. MRD-EDGECNV also reduces the degree of aneuploidy needed for ultrasensitive CNV detection through WGS from 1 Gb to 200 Mb, thereby expanding its applicability to a wider range of solid tumors. We harness the improved performance to identify MRD following surgery in multiple cancer types, track changes in tumor burden in response to neoadjuvant immunotherapy in non-small cell lung cancer (NSCLC) and demonstrate ctDNA shedding in precancerous colorectal adenomas. Finally, the radical signal-to-noise enrichment in MRD-EDGESNV enables de novo mutation calling in melanoma and small cell lung cancer (SCLC) without matched tumor, yielding clinically informative TF monitoring for patients on immune checkpoint inhibition (ICI).","abstract":"In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole genome sequencing (WGS). We now introduce MRD-EDGE, a composite machine learning-guided WGS ctDNA single nucleotide variant (SNV) and copy number variant (CNV) detection platform designed to increase signal enrichment. MRD-EDGESNV uses deep learning and a ctDNA-specific feature space to increase SNV signal-to-noise enrichment in WGS by 300X compared to previous WGS error suppression. MRD-EDGECNV also reduces the degree of aneuploidy needed for ultrasensitive CNV detection through WGS from 1 Gb to 200 Mb, thereby expanding its applicability to a wider range of solid tumors. We harness the improved performance to identify MRD following surgery in multiple cancer types, track changes in tumor burden in response to neoadjuvant immunotherapy in non-small cell lung cancer (NSCLC) and demonstrate ctDNA shedding in precancerous colorectal adenomas. Finally, the radical signal-to-noise enrichment in MRD-EDGESNV enables de novo mutation calling in melanoma and small cell lung cancer (SCLC) without matched tumor, yielding clinically informative TF monitoring for patients on immune checkpoint inhibition (ICI).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-31T04:08:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007546","title":"GLASS-NL DNA-Methylation","description":null,"abstract":"Low-grade IDH-mutant glioma are notoriously unpredictable and knowledge on the evolutionary trajectories is limited. The GLASS-NL consortium performed methylome profiling on paired initial and recurrent IDH-mutant astrocytoma tumours to elucidate the temporal changes in DNA-methylation. Whole-exome sequencing data and RNA-sequencing data from these samples are submitted separately.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-31T12:49:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007547","title":"Study of PD-1 negative CD8 effector T-cells in advanced HCC with single-cell sequencing","description":null,"abstract":"Immune checkpoint inhibitors (CPI) have dramatically changed the treatment landscape of advanced HCC (aHCC), but factors associated with response/resistance to CPI remain to be elucidated. The main aim of this project was to identify features associated with response and/or resistance to checkpoint inhibitors in advanced HCC at the single-cell resolution. We subjected both pre-treatment tissue biopsies and serial peripheral blood mononuclear cell (PBMC) samples of aHCC patients (n=44) treated with systemic therapy to droplet-based single-cell transcriptome (scRNAseq) and T-cell receptor sequencing (scTCRseq) using Chromium Single Cell V(D)J Solution. Doing so, we obtained high quality transcriptomic data for tissue biopsies and PBMC samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-08-31T21:25:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007548","title":"Tonsillitis Immunochip study","description":null,"abstract":"This is the tonsillitis genotype data from the following publication:\nThe Psoriasis Risk Allele HLA-C*06:02 Shows Evidence of Association with Chronic or Recurrent Streptococcal Tonsillitis\n\nhttps://pubmed.ncbi.nlm.nih.gov/30037793/\n\nAbstract: Pharyngeal tonsillitis is one of the most common upper respiratory tract infections, and group A streptococcus is the most important bacterial pathogen causing it. While most patients experience tonsillitis only rarely, a subset of patients suffers from recurrent or chronic tonsillitis or pharyngitis. The predisposing factors for recurring or chronic forms of this disease are not yet fully understood, but genetic predisposition has been suggested. A genetic association study using Illumina's Immunochip single-nucleotide polymorphism (SNP) array was performed to search for new genetic biomarkers in pharyngeal tonsillitis. More than 100,000 SNPs relevant to immune-mediated diseases were analyzed in a cohort of 95 patients subjected to tonsillectomy due to recurrent/chronic tonsillitis and 504 controls. Genetic association between the cases and controls showed strongest association with two peaks in the HLA locus (odds ratio [OR], 3.7 to 4.7; P = 4.9 × 10-6 to 5.7 × 10-6). Further analysis with imputed classical HLA alleles suggested the known psoriasis risk allele HLA-C*06:02 as a risk factor for tonsillitis (P = 4.8 × 10-4; OR, 2.3). In addition, the imputed HLA haplotype HLA-C*06:02/HLA-B*57:01, a reported risk haplotype in psoriasis, had the strongest risk for tonsillitis (P = 3.2 × 10-4; OR, 6.5). These findings further support the previously reported link between streptococcal throat infections and psoriasis.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007549","title":"Targeted_NanoSeq_across_species__multiple_tissues_","description":"Application of targeted nanoseq to various tissues from non-human species to learn about clonal evolution across the tree of life.","abstract":"Application of targeted nanoseq to various tissues from non-human species to learn about clonal evolution across the tree of life.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007550","title":"Effects of busulfan, fludarabine and clofarabine treatment on human small intestinal organoids generated from healthy donors","description":"The intestine is vulnerable to chemotherapy-induced toxicity due to its high epithelial proliferative rate, making gut toxicity an off-target effect in several cancer treatments, including conditioning regimens for allogeneic hematopoietic cell transplantation (HSCT). In HSCT, intestinal damage is an important factor in the development of Graft-versus-Host Disease (GVHD), an immune complication in which donor immune cells attack the recipient's tissues. Here, we developed a novel human intestinal organoid-based 3D model system to study the effects of chemotherapy-induced intestinal epithelial damage at the RNA level. We show that chemotherapy conditioning specifically reprograms the intestinal epithelial transcriptome after treatment with either busulfan (3.5μM), fludarabine (15μM) or clofarabine (0.5μM) for 24h. This knowledge can potentially enable us to understand which changes undergo in healthy tissues upon conditioning and how those are related with immune activation typical in GVHD.","abstract":"The intestine is vulnerable to chemotherapy-induced toxicity due to its high epithelial proliferative rate, making gut toxicity an off-target effect in several cancer treatments, including conditioning regimens for allogeneic hematopoietic cell transplantation (HSCT). In HSCT, intestinal damage is an important factor in the development of Graft-versus-Host Disease (GVHD), an immune complication in which donor immune cells attack the recipient's tissues. Here, we developed a novel human intestinal organoid-based 3D model system to study the effects of chemotherapy-induced intestinal epithelial damage at the RNA level. We show that chemotherapy conditioning specifically reprograms the intestinal epithelial transcriptome after treatment with either busulfan (3.5μM), fludarabine (15μM) or clofarabine (0.5μM) for 24h. This knowledge can potentially enable us to understand which changes undergo in healthy tissues upon conditioning and how those are related with immune activation typical in GVHD.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-01T09:08:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007551","title":"GLASS-NL RNA-sequencing Study","description":null,"abstract":"Low-grade IDH-mutant glioma are notoriously unpredictable and knowledge on the evolutionary trajectories is limited. The GLASS-NL consortium sequenced RNA from paired initial and recurrent IDH-mutant astrocytoma tumours to elucidate the temporal changes in gene expression. Whole-exome sequencing data and DNA-methylation array data from these samples are submitted separately.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-04-12T09:17:46.276019+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007552","title":"RNA sequencing in primary inflammatory (TPP) macrophages treated with a MEK1/2 inhibitor","description":"By investigating an intergenic haplotype on chr21q22, independently linked to inflammatory bowel disease (IBD), ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis, we discover that the causal gene, ETS2, is a master regulator of inflammatory responses in human macrophages and delineate how the risk haplotype increases ETS2 expression. Using a database of cellular signatures, we identified drugs that could modulate this pathway. To validate the anti-inflammatory activity of one class of small molecules in vitro, we treated TPP macrophages with vehicle control or a selective, non-ATP competitive MEK inhibitor (PD-0325901) at 2 doses (100nM and 500nM) and performed RNA sequencing.","abstract":"By investigating an intergenic haplotype on chr21q22, independently linked to inflammatory bowel disease (IBD), ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis, we discover that the causal gene, ETS2, is a master regulator of inflammatory responses in human macrophages and delineate how the risk haplotype increases ETS2 expression. Using a database of cellular signatures, we identified drugs that could modulate this pathway. To validate the anti-inflammatory activity of one class of small molecules in vitro, we treated TPP macrophages with vehicle control or a selective, non-ATP competitive MEK inhibitor (PD-0325901) at 2 doses (100nM and 500nM) and performed RNA sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-01T11:56:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007553","title":"RNA sequencing in primary inflammatory (TPP) macrophages following deletion of a disease-associated gene desert at chr21q22, disruption of ETS2, or treatment of ETS2-edited macrophages with a HIF1α stabiliser.","description":"GWAS studies in five different inflammatory diseases have identified a strong genetic association at a gene desert at the chr21q22 locus. We have shown that this locus contains a monocyte/macrophage-specific enhancer that regulates ETS2 - a gene whose role in primary human monocytes/macrophages is incompletely understood. We therefore used a CRISPR-Cas9-based approach to delete the enhancer region or to disrupt ETS2, and performed RNA-sequencing to examine the transcriptional consequences. One effect of ETS2 disruption was upregulation of genes involved in aerobic respiration and oxidative phosphorylation. We therefore treated ETS2-edited inflammatory macrophages with roxadustat, a HIF1α stabiliser that can promote glycolysis via HIF1α-mediated metabolic reprogramming, and performed RNA-sequencing to determine whether this drug might rescue the transcriptional effects of ETS2 disruption.","abstract":"GWAS studies in five different inflammatory diseases have identified a strong genetic association at a gene desert at the chr21q22 locus. We have shown that this locus contains a monocyte/macrophage-specific enhancer that regulates ETS2 - a gene whose role in primary human monocytes/macrophages is incompletely understood. We therefore used a CRISPR-Cas9-based approach to delete the enhancer region or to disrupt ETS2, and performed RNA-sequencing to examine the transcriptional consequences. One effect of ETS2 disruption was upregulation of genes involved in aerobic respiration and oxidative phosphorylation. We therefore treated ETS2-edited inflammatory macrophages with roxadustat, a HIF1α stabiliser that can promote glycolysis via HIF1α-mediated metabolic reprogramming, and performed RNA-sequencing to determine whether this drug might rescue the transcriptional effects of ETS2 disruption.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-01T11:57:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007554","title":"RNA sequencing in primary human macrophages overexpressing ETS2","description":"We investigated an intergenic haplotype on chr21q22, linked to five different inflammatory diseases, and discovered a mechanism that orchestrates macrophage responses during chronic inflammation. We delineated how the risk haplotype increases expression of the causal gene, ETS2, and demonstrated that ETS2 is necessary for inflammatory macrophage effector functions. To establish whether ETS2 is sufficient to drive inflammatory responses, we overexpressed ETS2 in a dose-dependent manner and performed RNA-sequencing to characterise the transcriptional effects.","abstract":"We investigated an intergenic haplotype on chr21q22, linked to five different inflammatory diseases, and discovered a mechanism that orchestrates macrophage responses during chronic inflammation. We delineated how the risk haplotype increases expression of the causal gene, ETS2, and demonstrated that ETS2 is necessary for inflammatory macrophage effector functions. To establish whether ETS2 is sufficient to drive inflammatory responses, we overexpressed ETS2 in a dose-dependent manner and performed RNA-sequencing to characterise the transcriptional effects.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-01T12:33:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007555","title":"Oxidative phosphorylation is a key ontogenetic feature of monocyte immunometabolism promoting myeloid differentiation after birth","description":"Neonates primarily rely on innate immunity, yet their inflammatory\nresponses to microbes, particularly those of monocytes, are usually restricted\ncompared to adults. This is controversially interpreted as immaturity increasing\nthe risk of sepsis or essential programming allowing immune adaptation after\nbirth. Which changes the cellular immunometabolism undergoes after birth and its role in these concepts are poorly defined.\nHere, we applied transcriptomic, metabolic, and immunological\napproaches and found that monocytes exhibit an\ninverse ontogenetic balance of immunometabolism. Our data show that glycolysis in\nmonocytes increases within the first year of life and fuels their inflammatory\nresponsiveness. In contrast, oxidative phosphorylation (OXPHOS) is high in\nneonatal monocytes supporting myeloid differentiation but declines only gradually\nduring the first five years of life. Treatment of neonatal monocytes with\nlipopolysaccharide induces an adult-like immunometabolic phenotype. Ketogenic\ndiet restricts glycolysis in adult monocytes, but cannot reactivate OXPHOS and\nrevive a neonatal-like immunometabolic phenotype, suggesting that neonatal\nmetabolism is hardwired and cannot be restored by simple dietary changes. Transcriptional\nnetwork and population-wide human variation analyses identified E2F1, MYB, STAT1 and FLI1 as important regulators of age-dependent cell functions and related energy demands in human monocytes.\nCollectively, our findings show that restricted glycolysis and increased OXPHOS are a physiological programming in neonatal monocytes. Premature switching to an adult-like metabolism could untimely enhance inflammatory responses and disrupt important myeloid differentiation, whereas microbial challenges accumulating during childhood seem to induce an essential gradual metabolic switch.","abstract":"Neonates primarily rely on innate immunity, yet their inflammatory\nresponses to microbes, particularly those of monocytes, are usually restricted\ncompared to adults. This is controversially interpreted as immaturity increasing\nthe risk of sepsis or essential programming allowing immune adaptation after\nbirth. Which changes the cellular immunometabolism undergoes after birth and its role in these concepts are poorly defined.\nHere, we applied transcriptomic, metabolic, and immunological\napproaches and found that monocytes exhibit an\ninverse ontogenetic balance of immunometabolism. Our data show that glycolysis in\nmonocytes increases within the first year of life and fuels their inflammatory\nresponsiveness. In contrast, oxidative phosphorylation (OXPHOS) is high in\nneonatal monocytes supporting myeloid differentiation but declines only gradually\nduring the first five years of life. Treatment of neonatal monocytes with\nlipopolysaccharide induces an adult-like immunometabolic phenotype. Ketogenic\ndiet restricts glycolysis in adult monocytes, but cannot reactivate OXPHOS and\nrevive a neonatal-like immunometabolic phenotype, suggesting that neonatal\nmetabolism is hardwired and cannot be restored by simple dietary changes. Transcriptional\nnetwork and population-wide human variation analyses identified E2F1, MYB, STAT1 and FLI1 as important regulators of age-dependent cell functions and related energy demands in human monocytes.\nCollectively, our findings show that restricted glycolysis and increased OXPHOS are a physiological programming in neonatal monocytes. Premature switching to an adult-like metabolism could untimely enhance inflammatory responses and disrupt important myeloid differentiation, whereas microbial challenges accumulating during childhood seem to induce an essential gradual metabolic switch.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-01T12:56:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007556","title":"Lower respiratory tract single cell and neutrophil extracellular trap profiling of COVID-19-associated pulmonary aspergillosis","description":null,"abstract":"COVID-19-associated pulmonary aspergillosis (CAPA) is a frequent, severe superinfection with the fungus Aspergillus affecting critically ill COVID-19 patients. The pathophysiology of this infection is still largely unknown. We performed an explorative study by performing single-cell RNA sequencing (scRNA-seq) on 43 bronchoalveolar lavage (BAL) fluid samples from 39 mechanically ventilated COVID-19 patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-01T14:41:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007557","title":"WGS data of an individual with Unicentric Castleman Disease","description":null,"abstract":"Whole-genome sequencing was done on the lymph node and blood samples from an individual with Unicentric Castleman Disease","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007558","title":"Detecting and quantifying clonal selection in somatic mosaicism","description":"In this study, we introduce a scalable method to identify clonal selection in an individual tissue, agnostic of the underlying mutations. To study clonal selection in the haematopoietic system, we performed whole genome sequencing on bone marrow CD34+ haematopoietic stem and progenitor cells from 22 non-leukemic individuals, 30-89 years of age. We performed 90x whole genome sequencing for all samples and re-sequenced 19 samples with sufficient DNA to a total target coverage of 270x. Whole genome sequencing of hair follicle DNA from the same individuals was used as germline control. In addition, we sequenced unseparated bone marrow mononuclear cells, CD3-CD34- bone marrow mononuclear cells, and peripheral blood granulocytes from 14 samples. Samples were collected from individuals undergoing hip replacement surgery as part of the Mechanisms of Age-Related Clonal Haematopoiesis (MARCH) Study (REC Ref: 17/YH/0382).","abstract":"In this study, we introduce a scalable method to identify clonal selection in an individual tissue, agnostic of the underlying mutations. To study clonal selection in the haematopoietic system, we performed whole genome sequencing on bone marrow CD34+ haematopoietic stem and progenitor cells from 22 non-leukemic individuals, 30-89 years of age. We performed 90x whole genome sequencing for all samples and re-sequenced 19 samples with sufficient DNA to a total target coverage of 270x. Whole genome sequencing of hair follicle DNA from the same individuals was used as germline control. In addition, we sequenced unseparated bone marrow mononuclear cells, CD3-CD34- bone marrow mononuclear cells, and peripheral blood granulocytes from 14 samples. Samples were collected from individuals undergoing hip replacement surgery as part of the Mechanisms of Age-Related Clonal Haematopoiesis (MARCH) Study (REC Ref: 17/YH/0382).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-03T09:37:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007559","title":"IMPRESS: Improved Methylation Profiling using Restriction Enzymes and smMIP Sequencing, Combined with New Biomarker Panel, Creating Multi-Cancer Detection Assay","description":null,"abstract":"We developed a methylation detection technique called IMPRESS (Improved Methylation Profiling using Restriction Enzymes and smMIP Sequencing), which combines four methylation-sensitive restriction enzymes (MSREs) and single-molecule Molecular Inversion Probes (MIPs) to capture DNA methylation. We used this technique for the development of a multi-cancer detection assay for eight of the most lethal cancer types worldwide. We selected 1,791 CpG sites that are at least 20% higher methylated in tumor tissue compared to normal tissue. These sites were analysed with the IMPRESS technique in 35 blood samples, 111 tumor samples and 114 normal samples. Finally, a classifier model was built to predict the status of each sample. \nWe present the successful development of IMPRESS. Validation of three target sites with ddPCR showed only small differences between the three targets, suggesting that IMPRESS performs at least equally well as a gold standard ddPCR technique. The final classifier model discriminating tumor from normal samples was built with 358 CpG target sites and reached a sensitivity of 0.95 and a specificity of 0.91. Importantly, we demonstrated IMPRESS’s applicability in cfDNA from liquid biopsies.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007560","title":"Determining genome-wide binding of ETS2 by CUT&RUN in primary human macrophages","description":null,"abstract":"We investigated an intergenic haplotype on chr21q22 that is associated with five different inflammatory diseases and discovered a mechanism that orchestrates macrophage responses during chronic inflammation. We delineated how the risk haplotype increases expression of the causal gene, ETS2, and showed that the pathway regulated by ETS2 is both necessary and sufficient for human macrophage responses during chronic inflammation. To better characterise ETS2 binding across the genome - and thereby identify ETS2 target genes - we performed Cleavage-Under-Targets-and-Release-Using-Nuclease (CUT&amp;RUN) in inflammatory (TPP) macrophages. Anti-ETS2 (ThermoFisher) or IgG control (Cell Signaling) antibodies were used for targeted digestion of chromatin. Library preparation was performed according to a protocols.IO protocol (dx.doi.org/10.17504/protocols.io.bagaibse) using the NEBNext Ultra II DNA Library Prep Kit. Size selection was performed using AMPure XP beads (Beckman Coulter) and fragment sizes were determined using an Agilent 2100 Bioanalyzer (High Sensitivity DNA kit). Equimolar pools of indexed libraries were sequenced. Raw data are provided as 100 bp paired-end Illumina reads from n = 2 donors.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-04T12:23:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007561","title":"Sequential Antigen-loss and Branching Evolution in Lymphoma after Anti-CD19 and Anti-CD20 Targeted T Cell Engaging Immunotherapy","description":"CD19 CAR T cells and CD20 targeting T cell engaging bispecific antibodies have been approved in B-cell Non-Hodgkin lymphoma lately, heralding a new clinical setting where patients are treated with both approaches, sequentially.  The aim of our study was to investigate the selective pressure of CD19 and CD20 directed therapy on the clonal architecture in lymphoma. Using a broad analytical pipeline, we identified truncating mutations in the gene encoding CD20 conferring antigen loss in 80% of patients relapsing from CD20 bispecs. Pronounced T cell exhaustion was identified in cases with progressive disease and retained CD20 expression. We also confirmed CD19 loss after CAR T cell therapy and report the case of sequential CD19 and CD20 loss. We observed branching evolution with re-emergence of CD20 positive subclones at later time points and spatial heterogeneity for CD20 expression in response to targeted therapy. Our results highlight immunotherapy as an evolutionary bottleneck selecting for antigen-loss variants but also complex evolutionary pathways underlying disease progression from these novel therapies.","abstract":"CD19 CAR T cells and CD20 targeting T cell engaging bispecific antibodies have been approved in B-cell Non-Hodgkin lymphoma lately, heralding a new clinical setting where patients are treated with both approaches, sequentially.  The aim of our study was to investigate the selective pressure of CD19 and CD20 directed therapy on the clonal architecture in lymphoma. Using a broad analytical pipeline, we identified truncating mutations in the gene encoding CD20 conferring antigen loss in 80% of patients relapsing from CD20 bispecs. Pronounced T cell exhaustion was identified in cases with progressive disease and retained CD20 expression. We also confirmed CD19 loss after CAR T cell therapy and report the case of sequential CD19 and CD20 loss. We observed branching evolution with re-emergence of CD20 positive subclones at later time points and spatial heterogeneity for CD20 expression in response to targeted therapy. Our results highlight immunotherapy as an evolutionary bottleneck selecting for antigen-loss variants but also complex evolutionary pathways underlying disease progression from these novel therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-04T12:51:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007562","title":"H3K27ac ChIP-seq in primary inflammatory (TPP) macrophages","description":"We investigated an intergenic haplotype on chr21q22, linked to five different inflammatory diseases, and identified the molecular mechanism by which the risk haplotype increases expression of the causal gene, ETS2. This mechanism was predicted to alter enhancer activity at the disease-associated locus. We therefore performed H3K27ac ChIP-seq in inflammatory macrophages from minor and major allele homozygotes at the causal allele and investigated the effect on enhancer activity.  In doing so, we mechanistically delineated how the risk haplotype increases expression of ETS2.","abstract":"We investigated an intergenic haplotype on chr21q22, linked to five different inflammatory diseases, and identified the molecular mechanism by which the risk haplotype increases expression of the causal gene, ETS2. This mechanism was predicted to alter enhancer activity at the disease-associated locus. We therefore performed H3K27ac ChIP-seq in inflammatory macrophages from minor and major allele homozygotes at the causal allele and investigated the effect on enhancer activity.  In doing so, we mechanistically delineated how the risk haplotype increases expression of ETS2.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-04T21:47:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007563","title":"Immune and clinicopathological features predict HER2-positive breast cancer prognosis in the neoadjuvant NeoALTTO and CALGB 40601 trials","description":"The identification of prognostic drivers in patients receiving neoadjuvant therapy is crucial for treatment optimization in HER2-positive breast cancer, with the immune microenvironment being a key factor. Here, we investigated the complexity of B and T cell receptor (BCR and TCR) repertoires, reflecting antigen-specific immune response, in the context of two phase III trials, namely NeoALTTO and CALGB 40601, evaluating neoadjuvant paclitaxel with trastuzumab and/or lapatinib in women affected by HER2-positive breast cancer. BCR/TCR features were heterogeneous, and BCR measures describing clonal expansion demonstrated independent prognostic value. A model developed in NeoALTTO and validated in CALGB 40601 predicted event-free survival (EFS) by integrating hormone receptor and clinical nodal status, treatment response (breast pCR)breast pathological complete response (pCR) as well as tumor-infiltrating lymphocytes and BCR evenness, measuring the equality of BCR clonal distribution. The HER2-EveNT score derived from the model allows the identification of patients with 5-year EFS &gt; 90%, and, in those not achieving pCR, of a subgroup of immune-enriched tumors with an excellent outcome despite residual disease.","abstract":"The identification of prognostic drivers in patients receiving neoadjuvant therapy is crucial for treatment optimization in HER2-positive breast cancer, with the immune microenvironment being a key factor. Here, we investigated the complexity of B and T cell receptor (BCR and TCR) repertoires, reflecting antigen-specific immune response, in the context of two phase III trials, namely NeoALTTO and CALGB 40601, evaluating neoadjuvant paclitaxel with trastuzumab and/or lapatinib in women affected by HER2-positive breast cancer. BCR/TCR features were heterogeneous, and BCR measures describing clonal expansion demonstrated independent prognostic value. A model developed in NeoALTTO and validated in CALGB 40601 predicted event-free survival (EFS) by integrating hormone receptor and clinical nodal status, treatment response (breast pCR)breast pathological complete response (pCR) as well as tumor-infiltrating lymphocytes and BCR evenness, measuring the equality of BCR clonal distribution. The HER2-EveNT score derived from the model allows the identification of patients with 5-year EFS &gt; 90%, and, in those not achieving pCR, of a subgroup of immune-enriched tumors with an excellent outcome despite residual disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-06T13:40:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007564","title":"Single cell multiomics of human spermatogenesis","description":null,"abstract":"Gametogenesis, the production of oocytes and sperm, ensures the faithful transmission of genetic material to the next generation. In males, spermatogenesis occurs in the testes, which contain the complete developmental progression of germ cells alongside the required supporting somatic cells. Defects in this fundamental process lead to infertility. However, the precise regulatory programs that govern spermatogenesis are unknown. The aim of this project is to identify the gene regulatory networks that drive human spermatogenesis.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007565","title":"Complex structural variation patterns in pediatric solid tumors","description":"In this study, we performed systematic characterization of  chromoplexy, chromothripsis and extrachromosomal DNA across five types of pediatric solid tumors: neuroblastoma, Ewing sarcoma, Wilms tumor, hepatoblastoma and rhabdomyosarcoma. Almost half of all tumors had at least one complex SV and we  identified candidate pathogenic events that affect genes or chromosomal alterations known to be relevant in these cancer types. In conclusion, complex SVs are prevalent and highly pathogenic in pediatric solid tumors.","abstract":"In this study, we performed systematic characterization of  chromoplexy, chromothripsis and extrachromosomal DNA across five types of pediatric solid tumors: neuroblastoma, Ewing sarcoma, Wilms tumor, hepatoblastoma and rhabdomyosarcoma. Almost half of all tumors had at least one complex SV and we  identified candidate pathogenic events that affect genes or chromosomal alterations known to be relevant in these cancer types. In conclusion, complex SVs are prevalent and highly pathogenic in pediatric solid tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-07T09:56:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007566","title":"Exome_NanoSeq__Pan_body_","description":"Exome NanoSeq in different tissues from a number of donors, both healthy and with pathology.","abstract":"Investigating the driver landscape in a range of tissues, in both health and disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007567","title":"Korea4K: whole genome sequences of 4,157 Koreans with 107 phenotypes derived from extensive health check-ups","description":null,"abstract":"Here, we present 4,157 whole-genome sequences (Korea4K) coupled with 107 health check-up parameters as the largest genomic resource of the Korean Genome Project. Collectively, Korea4K provides not only the largest Korean genome data but also corresponding health check-up parameters and novel genome-phenome associations. The large-scale pathological whole-genome-wide omics data will become a powerful set for genome-phenome level association studies to discover causal markers for the prediction and diagnosis of health conditions in future studies.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007568","title":"Mesenchymal niche in myelodysplastic hematopoiesis at single cell resolution","description":null,"abstract":"ExomeSequencing of bone marrow and germline samples","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007569","title":"Single-cell RNA-seq of peripheral blood mononuclear cells in classic Hodgkin lymphoma","description":"Classic Hodgkin lymphoma (cHL) is a largely MHC class I-negative tumor with recurrent 9p24.1/ PD-L1/ PD-L2 copy gains and the highest reported response rates to PD-1 blockade. We utilized scRNA sequencing to characterize the peripheral immune response to PD-1 blockade and more broadly define non-CD8+ dependent mechanisms of immune evasion in cHL. Peripheral blood mononuclear cells were obtained from 20 patients with relapsed/refractory (R/R) cHL treated with PD-1 blockade (nivolumab) on the CheckMate 205 clinical trial (paired samples from cycle 1 day 1 [C1D1] and cycle 4 day 1 [C4D1]), 11 patients with newly diagnosed, previously untreated cHL and 13 healthy donors.","abstract":"Classic Hodgkin lymphoma (cHL) is a largely MHC class I-negative tumor with recurrent 9p24.1/ PD-L1/ PD-L2 copy gains and the highest reported response rates to PD-1 blockade. We utilized scRNA sequencing to characterize the peripheral immune response to PD-1 blockade and more broadly define non-CD8+ dependent mechanisms of immune evasion in cHL. Peripheral blood mononuclear cells were obtained from 20 patients with relapsed/refractory (R/R) cHL treated with PD-1 blockade (nivolumab) on the CheckMate 205 clinical trial (paired samples from cycle 1 day 1 [C1D1] and cycle 4 day 1 [C4D1]), 11 patients with newly diagnosed, previously untreated cHL and 13 healthy donors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-10T05:05:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007570","title":"Single-cell RNA-seq of murine splenocytes from Bcl6tg/+ and Cd70-/-; Bcl6tg/+ diffuse large B-cell lymphoma mouse models and Cd70-/- and wild-type controls.","description":null,"abstract":"We previously defined 5 diffuse large B-cell lymphoma (DLBCL) clusters each with specific genetic alterations and identified potential genetic bases for immune evasion. In our series, CD70 inactivating mutations and copy loss were the most frequent potential genetic bases of immune evasion. CD70 mutations were significantly more abundant in Cluster 1, which also exhibited recurrent BCL6 translocations. CD70 activation of CD27+ T cells promotes T-cell expansion and immune surveillance of normal and malignant B cells. To assess the consequences of Cd70 deficiency and perturbed CD70/CD27 co-stimulation on Bcl6-driven lymphomagenesis, we crossed previously generated Bcl6tg/+ and Cd70-/- mice to obtain Cd70-/-; Bcl6tg/+ animals, which had a significantly increased incidence of DLBCL, largely involving the spleen. We utilized splenic scRNA sequencing to characterize the anti-tumor immune responses in Cd70-/-; Bcl6tg/+ and Bcl6tg/+ mice and compared them to Cd70-/- and wild-type controls. Spleens were harvested from 6 asymptomatic animals in each cohort at 6, 14 and 18 months and from 6-8 mice euthanized for lymphoma development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007571","title":"CS Baby Biome","description":null,"abstract":"CS Baby Biome randomized control trial aims to investigate if the timing of intrapartum antibiotics given to mother influences the infant gut microbiome composition. The study was performed in women delivering via elective CS, who received antibiotics prior to skin incision, or after umbilical cord clamping.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-11T10:56:40+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007572","title":"Cell culture differentiation and proliferation conditions influence the in vitro regeneration of the human airway epithelium","description":"The human airway mucociliary epithelium can be recapitulated in vitro using primary cells cultured in an Air-Liquid Interface (ALI), a reliable surrogate to perform pathophysiological studies. As tremendous variations exist between media used for ALI-cultured human airway epithelial cells, our study aimed to evaluate at a single-cell level the impact of several media (e.g. BEGMTM, PneumaCultTM, “Half&amp;Half” and “Clancy”) on cell type distribution. Our work revealed the impact of these media on cell composition, gene expression profile, cell signaling or epithelial shape. We found higher proportions of multiciliated cells in PneumaCultTM-ALI and Half&amp;Half, stronger EGF signaling from basal cells in BEGMTM-ALI, differential expression of the SARS-CoV-2 entry factor ACE2, and distinct secretomes transcripts depending on media used. We also established that proliferation in PneumaCultTM-Ex Plus favored secretory cells fate, showing the key influence of proliferation media on late differentiation epithelial characteristics. Altogether, our data offer a comprehensive repertoire for evaluating the effects of culture conditions on airway epithelial differentiation and will help to choose the most relevant medium according to the phenomenon to be investigated such as cilia or mucus biology or viral infection. We detail useful parameters that should be explored to document airway epithelial cell fate and shaping.","abstract":"The human airway mucociliary epithelium can be recapitulated in vitro using primary cells cultured in an Air-Liquid Interface (ALI), a reliable surrogate to perform pathophysiological studies. As tremendous variations exist between media used for ALI-cultured human airway epithelial cells, our study aimed to evaluate at a single-cell level the impact of several media (e.g. BEGMTM, PneumaCultTM, “Half&amp;Half” and “Clancy”) on cell type distribution. Our work revealed the impact of these media on cell composition, gene expression profile, cell signaling or epithelial shape. We found higher proportions of multiciliated cells in PneumaCultTM-ALI and Half&amp;Half, stronger EGF signaling from basal cells in BEGMTM-ALI, differential expression of the SARS-CoV-2 entry factor ACE2, and distinct secretomes transcripts depending on media used. We also established that proliferation in PneumaCultTM-Ex Plus favored secretory cells fate, showing the key influence of proliferation media on late differentiation epithelial characteristics. Altogether, our data offer a comprehensive repertoire for evaluating the effects of culture conditions on airway epithelial differentiation and will help to choose the most relevant medium according to the phenomenon to be investigated such as cilia or mucus biology or viral infection. We detail useful parameters that should be explored to document airway epithelial cell fate and shaping.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-11T15:41:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007573","title":"Low-coverage whole genome sequencing for a highly selective cohort of severe COVID-19 patients","description":"Background\nDespite advances in identification of genetic markers associated to severe COVID-19, the full genetic characterisation of the disease remains elusive. Imputation of low-coverage whole genome sequencing (lcWGS) has emerged as a competitive method to study such disease-related genetic markers as they enable genotyping of most common genetic variants used for genome wide association studies. This study aims at exploring the potential use of imputation in lcWGS for a highly selected severe COVID-19 patient cohort.\n\nFindings\nWe generated an imputed dataset of 79 variant call format (VCF) patient files using the GLIMPSE1 tool, each containing, on average, 9.5 million single nucleotide variants. The validation assessment of imputation accuracy yielded a squared Pearson correlation of approximately 0.97 across sequencing platforms, showing that GLIMPSE1 can be used to confidently impute variants with minor allele frequency up to approximately 2% in Spanish ancestry individuals. We conducted a comprehensive analysis on the patient cohort, examining hospitalisation and intensive care utilisation, sex and age-based differences, and clinical phenotypes using a standardised set of medical terms specifically developed to characterise severe COVID-19 symptoms for this cohort.\n\nConclusion\nThis dataset highlights the utility and accuracy of lcWGS imputation in the study of COVID-19 severity, setting a precedent for other applications in resource-constrained environments. The methods and findings presented here may be leveraged in future genomic projects, providing vital insights for health challenges like COVID-19.","abstract":"Background\nDespite advances in identification of genetic markers associated to severe COVID-19, the full genetic characterisation of the disease remains elusive. Imputation of low-coverage whole genome sequencing (lcWGS) has emerged as a competitive method to study such disease-related genetic markers as they enable genotyping of most common genetic variants used for genome wide association studies. This study aims at exploring the potential use of imputation in lcWGS for a highly selected severe COVID-19 patient cohort.\n\nFindings\nWe generated an imputed dataset of 79 variant call format (VCF) patient files using the GLIMPSE1 tool, each containing, on average, 9.5 million single nucleotide variants. The validation assessment of imputation accuracy yielded a squared Pearson correlation of approximately 0.97 across sequencing platforms, showing that GLIMPSE1 can be used to confidently impute variants with minor allele frequency up to approximately 2% in Spanish ancestry individuals. We conducted a comprehensive analysis on the patient cohort, examining hospitalisation and intensive care utilisation, sex and age-based differences, and clinical phenotypes using a standardised set of medical terms specifically developed to characterise severe COVID-19 symptoms for this cohort.\n\nConclusion\nThis dataset highlights the utility and accuracy of lcWGS imputation in the study of COVID-19 severity, setting a precedent for other applications in resource-constrained environments. The methods and findings presented here may be leveraged in future genomic projects, providing vital insights for health challenges like COVID-19.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-11T16:31:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007574","title":"Idiosyncratic and generic single nuclei and spatial transcriptional patterns in papillary and anaplastic thyroid cancers","description":"Thyroid cancer is the most common endocrine malignancy. This dataset encompasses two types of thyroid cancer : anaplastic which is the most de-differentiated and aggressive one, and papillary which is the most common one. We profiled 14 patients, including 10 papillary and 4 anaplastic thyroid carcinomas, using both single nuclei RNA sequencing and spatial transcriptomics to link single cell resolution RNA sequencing with tissue morphology and better understand inter and intratumoral thyroid cancer heterogeneity.","abstract":"Thyroid cancer is the most common endocrine malignancy. This dataset encompasses two types of thyroid cancer : anaplastic which is the most de-differentiated and aggressive one, and papillary which is the most common one. We profiled 14 patients, including 10 papillary and 4 anaplastic thyroid carcinomas, using both single nuclei RNA sequencing and spatial transcriptomics to link single cell resolution RNA sequencing with tissue morphology and better understand inter and intratumoral thyroid cancer heterogeneity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-11T18:05:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007575","title":"Structural and Non-Coding Variants Increase the Diagnostic Yield of Clinical Whole Genome Sequencing for Rare Diseases","description":null,"abstract":"Although whole genome sequencing is increasingly used for the diagnosis of patients with rare disease, diagnostic yields often disappointingly low. We undertook WGS on a cohort of 122 unrelated RD patients and applied a bioinformatics pipeline that would allow an in-depth interrogation of the genome to provide a comprehensive analysis of all variant types. Our results demonstrate that structural, splice-site and intronic variants make a substantial contribution to diagnostic yield and therefore that comprehensive analysis of the entire genome is essential to maximise the value of clinical WGS.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-13T09:20:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007576","title":"Single Cell Track and Trace: live cell labelling and temporal transcriptomics via nanobiopsy","description":null,"abstract":"Single-cell RNA sequencing has revolutionised our understanding of cellular heterogeneity, but whether using isolated cells or more recent spatial transcriptomics approaches, these methods require isolation and lysis of the cell under investigation. This provides a snapshot of the cell transcriptome from which dynamic trajectories, such as those that trigger cell state transitions, can only be inferred. Here, we present cellular nanobiopsy: a platform that enables simultaneous labelling and sampling from a single cell without killing it. The technique is based on scanning ion conductance microscopy (SICM) and uses a double-barrel nanopipette with one barrel able to inject a fluorescent dye and the other used as an electrochemical syringe to extract femtolitre-volumes of cytosol. We used the nanobiopsy to longitudinally profile the transcriptome of single glioblastoma (GBM) brain tumour cells in vitro over 72hrs with and without standard treatment. Our results suggest that treatment either induces or selects for more transcriptionally stable cells. We envision the nanobiopsy will transform standard single-cell transcriptomics from a static analysis into a dynamic and temporal assay.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007577","title":"CDK4 phosphorylation status and rational use for combining CDK4/6 and BRAF/MEK inhibition in advanced thyroid carcinomas","description":null,"abstract":"Background: CDK4/6 inhibitors (CDK4/6i) have been established as standard treatment against advanced Estrogen Receptor-positive breast cancers. These drugs are being tested against several cancers, including in combinations with other therapies. We identified the T172-phosphorylation of CDK4 as the step determining its activity, retinoblastoma protein (RB) inactivation, cell cycle commitment and sensitivity to CDK4/6i. Poorly differentiated (PDTC) and anaplastic (ATC) thyroid carcinomas, the latter considered one of the most lethal human malignancies, represent major clinical challenges. Several molecular evidence suggest that CDK4/6i could be considered for treating these advanced thyroid cancers.\nMethods: We analyzed by two-dimensional gel electrophoresis the CDK4 modification profile and the presence of T172-phosphorylated CDK4 in a collection of 98 fresh-frozen tissues and in 21 cell lines. A sub-cohort of samples was characterized by RNA sequencing and immunohistochemistry. Sensitivity to CDK4/6i (palbociclib and abemaciclib) was assessed by BrdU incorporation/viability assays. Treatment of cell lines with CDK4/6i and combination with BRAF/MEK inhibitors (dabrafenib/trametinib) was comprehensively evaluated by western blot, characterization of immunoprecipitated CDK4 and CDK2 complexes and clonogenic assays.\nResults: CDK4 phosphorylation was detected in all well-differentiated thyroid carcinomas (n=29), 19/20 PDTC, 16/23 ATC and 18/21 thyroid cancer cell lines, including 11 ATC-derived ones. Tumors and cell lines without phosphorylated CDK4 presented very high p16CDKN2A levels, which were associated with proliferative activity. Absence of CDK4 phosphorylation in cell lines was associated with CDK4/6i insensitivity. RB1 defects (the primary cause of intrinsic CDK4/6i resistance) were not found in 5/7 tumors without detectable phosphorylated CDK4. A previously developed 11-gene expression signature identified the likely unresponsive tumors, lacking CDK4 phosphorylation. In cell lines, palbociclib synergized with dabrafenib/trametinib by completely and permanently arresting proliferation. These combinations prevented resistance mechanisms induced by palbociclib, most notably Cyclin E1-CDK2 activation and a paradoxical stabilization of phosphorylated CDK4 complexes.\nConclusion: Our study supports further clinical evaluation of CDK4/6i and their combination with anti-BRAF/MEK therapies as a novel effective treatment against advanced thyroid tumors. Moreover, the complementary use of our 11 genes predictor with p16/KI67 evaluation could represent a prompt tool for recognizing the intrinsically CDK4/6i insensitive patients, who are potentially better candidates to immediate chemotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-14T14:57:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007578","title":"Peripheral blood DNA methylome in adalimumab-treated patients with rheumatoid arthritis","description":"Background and aims\nRheumatoid arthritis (RA) patients are currently treated with biological agents mostly aimed at cytokine blockade such as anti-TNFα therapy. Currently, there are no biomarkers to predict therapy response to these agents. Here, we aimed to predict response to adalimumab (ADA) treatment in RA patients using DNA methylation in peripheral blood\n\nMethods\nDNA methylation profiling on whole peripheral blood from 92 RA patients before the start of  adalimumab (ADA) was determined using Illumina HumanMethylationEPIC BeadChip Array. After 6 months, treatment response was assessed according to the Alliance of Associations for Rheumatology (EULAR) criteria for disease response. Patients were classified as responders (DAS28&lt;3.2 or decrease of 1.2 points) or as non-responders (DAS28&gt;5.1 or decrease of less than 0.6 points). Machine learning models were built with gradient boosting and stability selection models to predict response prior to ADA treatment with predictor DNA methylation markers.\n\nResults\nWe demonstrated a 27-feature panel of DNA methylation markers or CpG classifiers that predict response in RA patients treated with ADA. Forty-nine patients were assigned as responder and 43 patients assigned as non-responders. We differentiate responders from non-responders with a high sensitivity (AUC 0.76). The predictor CpGs annotated to genes involved in immunological- and pathophysiological pathways related to RA such as T-cell signaling, B-cell pathology and angiogenesis.\n\nConclusion\nOur findings indicate that DNA methylation signatures discriminate responders and non-responders to ADA treatment and can serve as a tool for therapy prediction.","abstract":"Background and aims\nRheumatoid arthritis (RA) patients are currently treated with biological agents mostly aimed at cytokine blockade such as anti-TNFα therapy. Currently, there are no biomarkers to predict therapy response to these agents. Here, we aimed to predict response to adalimumab (ADA) treatment in RA patients using DNA methylation in peripheral blood\n\nMethods\nDNA methylation profiling on whole peripheral blood from 92 RA patients before the start of  adalimumab (ADA) was determined using Illumina HumanMethylationEPIC BeadChip Array. After 6 months, treatment response was assessed according to the Alliance of Associations for Rheumatology (EULAR) criteria for disease response. Patients were classified as responders (DAS28&lt;3.2 or decrease of 1.2 points) or as non-responders (DAS28&gt;5.1 or decrease of less than 0.6 points). Machine learning models were built with gradient boosting and stability selection models to predict response prior to ADA treatment with predictor DNA methylation markers.\n\nResults\nWe demonstrated a 27-feature panel of DNA methylation markers or CpG classifiers that predict response in RA patients treated with ADA. Forty-nine patients were assigned as responder and 43 patients assigned as non-responders. We differentiate responders from non-responders with a high sensitivity (AUC 0.76). The predictor CpGs annotated to genes involved in immunological- and pathophysiological pathways related to RA such as T-cell signaling, B-cell pathology and angiogenesis.\n\nConclusion\nOur findings indicate that DNA methylation signatures discriminate responders and non-responders to ADA treatment and can serve as a tool for therapy prediction.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-17T07:46:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007579","title":"Degeneration of Lung Capillary Endothelial Cells in Pulmonary Arterial Hypertension","description":null,"abstract":"Pulmonary arterial hypertension (PAH) involves progressive cellular accumulation leading to obstructive remodeling of the pulmonary microvasculature. To understand this process, we analyzed parenchymal samples from 7 idiopathic PAH patients and 7 controls using single-nucleus (snRNAseq) and spatial transcriptomics (MERFISH). Our snRNA-Seq dataset comprising 71,530 cells, reveals 39 distinct cell-types, cross-referenced with the human lung cell atlas v.1. These analyses identify reductions in microvascular endothelial cells and specific subtypes of monocytes/macrophages infiltrating airspaces, characteristic of late-stage PAH. MERFISH experiments confirm capillary loss in PAH, with significant alterations in BMP/TGF and endothelin signaling, as well as glutamine synthesis. Macrophage adhesion, aggregation, and activation, coincide with remodeling of the distal pulmonary vessels, supporting these findings.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-18T09:06:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007580","title":"Korea4K: whole genome sequences of 4,157 Koreans with 107 phenotypes derived from extensive health check-ups","description":"Here, we present 4,157 whole-genome sequences (Korea4K) coupled with 107 health check-up parameters as the largest genomic resource of the Korean Genome Project. Collectively, Korea4K provides not only the largest Korean genome data but also corresponding health check-up parameters and novel genome-phenome associations. The large-scale pathological whole-genome-wide omics data will become a powerful set for genome-phenome level association studies to discover causal markers for the prediction and diagnosis of health conditions in future studies.","abstract":"Here, we present 4,157 whole-genome sequences (Korea4K) coupled with 107 health check-up parameters as the largest genomic resource of the Korean Genome Project. Collectively, Korea4K provides not only the largest Korean genome data but also corresponding health check-up parameters and novel genome-phenome associations. The large-scale pathological whole-genome-wide omics data will become a powerful set for genome-phenome level association studies to discover causal markers for the prediction and diagnosis of health conditions in future studies.","study_type":"Other","pubmed_ids":[38626723],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007581","title":"whole exome sequencing of lung adenocarcinoma","description":null,"abstract":"Little is known of the geospatial architecture of individual cell populations in lung adenocarcinoma (LUAD) evolution. Here, we performed whole exome sequencing of one LUAD, in addition to single-cell RNA sequencing of cells from 16 LUADs and 47 multi-region normal lung tissues of defined spatial proximities from the tumors. Our multi-region single-cell sequencing analyses unravel cell populations, states, and phenotypes in the spatial and ecological evolution LUAD from the lung that comprise high-potential targets for early interception.","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007582","title":"Establishment and characterization of circulating tumor cells-derived organoids from metastatic breast cancer patients.","description":"Over the last decade, molecular stratification and associated therapies have greatly improved the treatment options and prognosis of patients diagnosed with breast cancer. However, metastatic disease remains incurable. Breast cancer cells mainly spread to the lung, liver, bone and brain and circulating tumor cells (CTCs) that migrate in the lymphatics or blood have been implicated as the cellular source of metastasis. Detailed molecular and functional characterization of patient CTCs remains poor due to their low number in patient’s bloodstream. In addition, CTCs are difficult to culture and expand ex vivo. Here we have established a novel method for culturing and unlimitedly expanding breast cancer patient-derived CTCs in CTC-derived organoids (CDOs). Our platform can serve as a foundation for serial longitudinal isolation and expansion of breast cancer cells from peripheral blood. This may enable the identification and functional validation of therapy resistance mechanisms during disease progression, which can be used for new approaches in precision medicine.","abstract":"Over the last decade, molecular stratification and associated therapies have greatly improved the treatment options and prognosis of patients diagnosed with breast cancer. However, metastatic disease remains incurable. Breast cancer cells mainly spread to the lung, liver, bone and brain and circulating tumor cells (CTCs) that migrate in the lymphatics or blood have been implicated as the cellular source of metastasis. Detailed molecular and functional characterization of patient CTCs remains poor due to their low number in patient’s bloodstream. In addition, CTCs are difficult to culture and expand ex vivo. Here we have established a novel method for culturing and unlimitedly expanding breast cancer patient-derived CTCs in CTC-derived organoids (CDOs). Our platform can serve as a foundation for serial longitudinal isolation and expansion of breast cancer cells from peripheral blood. This may enable the identification and functional validation of therapy resistance mechanisms during disease progression, which can be used for new approaches in precision medicine.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-19T10:37:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007583","title":"WXS Tumor Samples Javelin head and neck 100","description":null,"abstract":"Immune checkpoint blockade (ICB) has improved patient outcomes in \nmultiple cancers, including head and neck squamous cell carcinomas \n(HNSCC), yet many patients do not benefit. Combination therapies \nintegrating immunotherapy are benefitting patients but the drivers of \nefficacy are not understood.  Here we report genomic, microenvironmental, and tumor microbiome \ncorrelates of efficacy to avelumab combined with standard of care \nchemoradiotherapy (CRT) in the phase 3 randomized, double-blinded, \nplacebo-controlled study in patients with locally advanced squamous \ncell carcinoma of the head and neck JAVELIN Head and Neck 100 \n(NCT02952586).","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-22T08:37:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007584","title":"Germline variants in patients diagnosed with both uveal and cutaneous melanoma","description":"We sequenced the constitutional DNA from patients affected by both uveal and cutaneous melanoma.","abstract":"We sequenced the constitutional DNA from patients affected by both uveal and cutaneous melanoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-22T13:07:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007585","title":"Exploring the cell-free total RNA transcriptome in diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma patients as biomarker source in blood plasma liquid biopsies","description":"The goal of this study was to investigate cell-free RNA (cfRNA) biomarkers in DLBCL and PMBCL patients. Blood plasma samples (n=168) and matched diagnostic formalin-fixed paraffin-embedded (FFPE) tissue samples (n=69) of DLBCL patients, PMBCL patients and healthy controls were collected between 2016-2021. Plasma samples were collected at diagnosis, at interim evaluation, after treatment, and in case of refractory or relapsed disease. RNA was extracted from 200 µl plasma using the miRNeasy serum/plasma kit and from FFPE tissue using the miRNeasy FFPE kit. RNA was subsequently sequenced on a NovaSeq 6000 instrument using the SMARTer Stranded Total RNA-seq pico v3 library preparation kit.","abstract":"The goal of this study was to investigate cell-free RNA (cfRNA) biomarkers in DLBCL and PMBCL patients. Blood plasma samples (n=168) and matched diagnostic formalin-fixed paraffin-embedded (FFPE) tissue samples (n=69) of DLBCL patients, PMBCL patients and healthy controls were collected between 2016-2021. Plasma samples were collected at diagnosis, at interim evaluation, after treatment, and in case of refractory or relapsed disease. RNA was extracted from 200 µl plasma using the miRNeasy serum/plasma kit and from FFPE tissue using the miRNeasy FFPE kit. RNA was subsequently sequenced on a NovaSeq 6000 instrument using the SMARTer Stranded Total RNA-seq pico v3 library preparation kit.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-25T15:08:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007586","title":"Targeted_NanoSeq__FAP_cohort_","description":"Targeted NanoSeq of fresh buccal swabs obtained from patients with inherited tumour predisposition syndromes (Familial Adenomatous Polyposis (FAP)). A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the buccal driver landscape in patients with inherited tumour predisposition syndromes (FAP).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007587","title":"RE_NanoSeq__Supernatants_","description":"RE-NanoSeq in epithelial cultures grown in-vitro from healthy epithelium such as bladder urothelium and oral epithelia. Samples obtained include the original colony and supernatants extracted containing cells at time points and different exposure. RE-NanoSeq will be used to determine whether exposures alter the mutation burden or mutational signatures of the cultured cells.","abstract":"RE-NanoSeq in epithelial cultures grown in-vitro from healthy epithelium such as bladder urothelium and oral epithelia. Samples obtained include the original colony and supernatants extracted containing cells at time points and different exposure. RE-NanoSeq will be used to determine whether exposures alter the mutation burden or mutational signatures of the cultured cells.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007588","title":"Birth_Cohort_BiB","description":"Wellcome Sanger Institute (WSI) proposes to exome sequence approximately 34,500 individuals from the ALSPAC, Born in Bradford (BiB) and Fenland cohorts. This proposal will supplement WSI core-funding from the Wellcome Trust to enable comprehensive sequencing of the ALSPAC and BiB cohorts. This proposal builds upon exome sequencing of subsets of the ALSPAC and BiB cohorts that has been conducted at WSI over the past 18 months.","abstract":"The ALSPAC and BiB datasets are world-leading cohorts with respect to multi-dimensional longitudinal assessment of child development, and as such they complement existing UK adult cohort data assets such as the UKBiobank exome and genome sequencing data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-09-28T16:20:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007589","title":"Prediction of tumor-specific splicing from somatic mutations as a source of neoantigen candidates","description":"Splicing is dysregulated in many tumors and may result in tumor-specific transcripts that can encode neoantigens, which are promising targets for cancer immunotherapy. Detecting tumor-specific splicing is challenging because many non-canonical splice junctions identified in tumor transcriptomes also appear in healthy tissues. However, somatic mutations can disrupt canonical splicing motifs or create novel ones leading to true tumor-specific targets.\n\nHere, we developed splice2neo to integrate the predicted splice effects from somatic mutations with splice junctions detected in tumor RNA-seq for individual cancer patients. Using splice2neo, we excluded canonical splice junctions and splice junctions from healthy tissue samples, annotated resulting transcript and peptide sequences, and integrated targeted re-quantification of supporting RNA-seq reads. By analyzing melanoma patient cohorts, we established a stringent detection rule to predict splice junctions as mutation-derived and tumor-specific targets. In an independent melanoma cohort, we identified 1.7 target splice junctions per tumor with an estimated false discovery rate of less than 5% and established tumor-specificity using additional healthy tissue samples. For individual examples of exon skipping events, we confirmed the expression in tumor-derived RNA by quantitative real-time PCR experiments. Most target splice junctions encoded at least one neoepitope candidate with predicted MHC-I or MHC-II binding. Compared to neoepitope candidates derived from non-synonymous point mutations, the splicing-derived neoepitope candidates had a lower self-similarity to corresponding wild-type peptides.\n\nIdentifying mutation-derived and tumor-specific splice junctions can lead to additional neoantigen candidates to expand the target repertoire for cancer immunotherapies.","abstract":"Splicing is dysregulated in many tumors and may result in tumor-specific transcripts that can encode neoantigens, which are promising targets for cancer immunotherapy. Detecting tumor-specific splicing is challenging because many non-canonical splice junctions identified in tumor transcriptomes also appear in healthy tissues. However, somatic mutations can disrupt canonical splicing motifs or create novel ones leading to true tumor-specific targets.\n\nHere, we developed splice2neo to integrate the predicted splice effects from somatic mutations with splice junctions detected in tumor RNA-seq for individual cancer patients. Using splice2neo, we excluded canonical splice junctions and splice junctions from healthy tissue samples, annotated resulting transcript and peptide sequences, and integrated targeted re-quantification of supporting RNA-seq reads. By analyzing melanoma patient cohorts, we established a stringent detection rule to predict splice junctions as mutation-derived and tumor-specific targets. In an independent melanoma cohort, we identified 1.7 target splice junctions per tumor with an estimated false discovery rate of less than 5% and established tumor-specificity using additional healthy tissue samples. For individual examples of exon skipping events, we confirmed the expression in tumor-derived RNA by quantitative real-time PCR experiments. Most target splice junctions encoded at least one neoepitope candidate with predicted MHC-I or MHC-II binding. Compared to neoepitope candidates derived from non-synonymous point mutations, the splicing-derived neoepitope candidates had a lower self-similarity to corresponding wild-type peptides.\n\nIdentifying mutation-derived and tumor-specific splice junctions can lead to additional neoantigen candidates to expand the target repertoire for cancer immunotherapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007590","title":"SMARCB1 loss activates patient-specific distal oncogenic enhancers in malignant rhabdoid tumors","description":"Malignant rhabdoid tumor (MRT) is a highly malignant and often lethal childhood cancer. MRTs are genetically defined by bi-allelic inactivating mutations in SMARCB1, a member of the BRG1/BRM-associated factors (BAF) chromatin remodeling complex. Mutations in BAF complex members are common in human cancer, yet their contribution to tumorigenesis remains in many cases poorly understood. Here, we studied derailed regulatory landscapes as a consequence of SMARCB1 loss in the context of MRT. Our multi-omics approach on patient-derived MRT organoids revealed a dramatic reshaping of the regulatory landscape upon SMARCB1 reconstitution. Chromosome conformation capture experiments subsequently revealed patient-specific looping of distal enhancer regions with the promoter of the MYC oncogene. This intertumoral heterogeneity in MYC enhancer utilization is also present in patient MRT tissues as shown by combined single-cell RNA-seq and ATAC-seq. We show that loss of SMARCB1 drives patient-specific epigenetic reprogramming underlying MRT tumorigenesis.","abstract":"Malignant rhabdoid tumor (MRT) is a highly malignant and often lethal childhood cancer. MRTs are genetically defined by bi-allelic inactivating mutations in SMARCB1, a member of the BRG1/BRM-associated factors (BAF) chromatin remodeling complex. Mutations in BAF complex members are common in human cancer, yet their contribution to tumorigenesis remains in many cases poorly understood. Here, we studied derailed regulatory landscapes as a consequence of SMARCB1 loss in the context of MRT. Our multi-omics approach on patient-derived MRT organoids revealed a dramatic reshaping of the regulatory landscape upon SMARCB1 reconstitution. Chromosome conformation capture experiments subsequently revealed patient-specific looping of distal enhancer regions with the promoter of the MYC oncogene. This intertumoral heterogeneity in MYC enhancer utilization is also present in patient MRT tissues as shown by combined single-cell RNA-seq and ATAC-seq. We show that loss of SMARCB1 drives patient-specific epigenetic reprogramming underlying MRT tumorigenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-10-02T13:39:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007591","title":"Massively_parallel_mutagenesis_of_human_transcription_factors___1__Pilot_Project","description":"Transcription factors (TF) play key roles in physiology and disease, yet most TF mutations documented in ClinVar (70%, 4681 missense variants) are classified as uncertain significance. In addition, targeting TFs is generally considered ‘undruggable’. To tackle these challenges, we aim to build reference atlases of TF variant effects to discriminate pathological from benign variants and to systematically identify allosteric sites in TFs for a potentially druggable therapeutic target. In this pilot study proposal, we will set up experimental pipelines to systematically examine mutational effects in 10 diverse human TF and their DNA-binding domains. We will do so by combining massively parallel mutagenesis with two sets of bacteria-based assays, one to examine the stability (Spectinomycin ‘tripartite’ sandwich assay) and the other to examine the DNA-binding (bacterial one-hybrid assay).","abstract":"Transcription factors (TF) recognize and bind to specific DNA sequences to regulate gene expression. TFs play key roles in physiology and disease. So far, 6,679 missense variants are documented in TFs in ClinVar (search in Jan 2023) with 70% (4681 missense variants) classified as uncertain significance. TFs lack enzymatic activity and function via molecular recruitment (protein-protein interactions) and so are considered very challenging drug targets or ‘undruggable’ (Henley and Koehler 2021). The major exception to this is the nuclear receptor (NR) family of TFs (e.g. oestrogen receptor) that bind small molecule ligands (hormones) that allosterically activate or inhibit their activity.  These natural allosteric sites of NRs have been successfully targeted with many different clinically approved small molecules to activate or inhibit their activity, making them major drug targets.\n\nTwo major challenges in TF research are: (1) to build reference atlases of variant effects to discriminate pathological from benign variants and to determine disease variant mechanisms of action and (2) to systematically identify allosteric sites in TFs.  The identification of an allosterically active surface pocket on a TF would transform it from being considered an undruggable to a potentially druggable therapeutic target.\n\nIn the Lehner lab, we have previously developed the first general approach to identifying allosteric sites in proteins. The method uses ‘multi-dimensional’ mutagenesis where the effects of mutations are quantified on both the molecular activity of a protein (e.g. binding) and its abundance (solubility).  Repeating this in multiple genetic backgrounds (e.g. shallow double mutagenesis) provides sufficient experimental data to infer the underlying causal biophysical effects of mutations (free energies of folding and binding), allowing the global mapping of allosteric communication in a protein (Faure et al. 2022; Weng et al. 2022).  \n\nHere we will apply this strategy to human TFs, using DNA-binding as the functional readout of protein activity. This proposal is to perform a pilot study to set up the experimental pipeline and to produce (1) reference variant effect maps and (2) allosteric atlases for 10 diverse human TF DNA-binding domains.  If successful, we will then submit a second RCP to scale the project to target hundreds of human TFs","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007592","title":"Lifelines-NEXT newborn cohort","description":null,"abstract":"The Lifelines-NEXT is a cohort of newborns followed up from birth up to the age of 1 year and later. The cohort includes approximately 1,500 newborns and their mothers from the 3 provinces of the Northern Netherlands.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007593","title":"Low-coverage whole-genome sequencing of cancer and healthy plasma circulating DNA","description":null,"abstract":"Plasma samples from patients with melanoma (stage II/III/IV) and breast cancer (stage IV) as well as healthy individuals were subjected to  low-coverage whole-genome sequencing (less than 10x average depth).","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-10-03T14:58:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007594","title":"RE_NanoSeq___TwinsUK_Blood","description":"Utilising restriction enzyme NanoSeq, we hope to explore the somatic mutation burden and mutational signatures in blood from TwinsUK donors. These donors have paired buccal swabs and data from this will help contextualise that work.","abstract":"Investigating the somatic mutation landscape, particularly the mutation burden and mutational signatures, in twins with paired buccal swabs.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007595","title":"Targeted_NanoSeq___TwinsUK_Blood","description":"Utilising Targeted NanoSeq, we hope to explore the driver landscape in unprecedented detail in donors from TwinsUK. These donors have paired buccal swabs and data from this will help contextualise that work.","abstract":"Investigating the driver landscape in blood from twins with paired buccal swabs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-10-04T08:29:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007596","title":"Exome_NanoSeq___Sorted_Blood","description":"Exome NanoSeq to explore the driver landscape in sorted blood populations from donors in health and disease.","abstract":"Exploring the driver landscape in individual populations of cells from blood, across health, disease, and ageing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007597","title":"Identification of nonsense mediated decay inhibitors that can alter the tumor immune landscape","description":"Despite exciting developments in cancer immunotherapy, its broad application is limited by the paucity of targetable antigens on the cell surface. As an intrinsic cellular pathway, nonsense mediated decay (NMD) conceals neoantigens through the destruction of the RNA products from genes harboring truncating mutations. Here we report the development of a new high throughput screen, based on the ratiometric analysis of transcripts. This screen revealed a previously known drug, LY3023414, as a potent disruptor of NMD and traced its effectiveness to its capacity to inhibit SMG1’s phosphorylation of UPF1. This led us to design a novel SMG1 inhibitor, KVS0001, and demonstrate it elevates expression of transcripts and proteins resulting from truncating mutations in vivo and in vitro. Most importantly, KVS0001 concomitantly increased the presentation of HLA class I-associated peptides from NMD-downregulated proteins on the surface of cancer cells. KVS0001 provides new opportunities for studying NMD and the diseases in which NMD plays a role, including cancer and inherited diseases.","abstract":"Despite exciting developments in cancer immunotherapy, its broad application is limited by the paucity of targetable antigens on the cell surface. As an intrinsic cellular pathway, nonsense mediated decay (NMD) conceals neoantigens through the destruction of the RNA products from genes harboring truncating mutations. Here we report the development of a new high throughput screen, based on the ratiometric analysis of transcripts. This screen revealed a previously known drug, LY3023414, as a potent disruptor of NMD and traced its effectiveness to its capacity to inhibit SMG1’s phosphorylation of UPF1. This led us to design a novel SMG1 inhibitor, KVS0001, and demonstrate it elevates expression of transcripts and proteins resulting from truncating mutations in vivo and in vitro. Most importantly, KVS0001 concomitantly increased the presentation of HLA class I-associated peptides from NMD-downregulated proteins on the surface of cancer cells. KVS0001 provides new opportunities for studying NMD and the diseases in which NMD plays a role, including cancer and inherited diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007598","title":"Integrative Multi-Omics Enhancer Activity Profiling Identifies Therapeutic Vulnerabilities in Cholangiocarcinoma of Different Etiologies","description":"Objectives: Cholangiocarcinoma (CCA) is a heterogeneous malignancy with high mortality and dismal prognosis, and an urgent clinical need for new therapies. Knowledge of the CCA epigenome is largely limited to aberrant DNA methylation. Dysregulation of enhancer activities has been identified to affect carcinogenesis and leveraged for new therapies but is uninvestigated in CCA. Our aim is to identify potential therapeutic targets in different subtypes of CCA through enhancer profiling.\nDesign: Integrative multi-omics enhancer activity profiling of diverse CCA was performed. A panel of diverse CCA cell lines, patient-derived and cell line-derived xenografts were used to study identified enriched pathways and vulnerabilities. NanoString, multiplex immunohistochemistry staining and single-cell spatial transcriptomics were used to explore immunogenicity of diverse CCA.\nResults: We identified 3 distinct groups, associated with different etiologies and unique pathways. Drug inhibitors of identified pathways reduced tumor growth in in-vitro and in-vivo models. The first group (ESTRO), with mostly fluke-associated CCAs, displayed activation in estrogen signaling and were sensitive to MTOR inhibitors. Another group (OXPHO), with mostly BAP1 and IDH-mutant CCAs, displayed activated oxidative phosphorylation pathways, and were sensitive to oxidative phosphorylation inhibitors. Immune-related pathways were activated in the final group (IMMUN), made up of an immunogenic CCA subtype and CCA with aristolochic acid (AA) mutational signatures. Intra-tumor differences in AA mutation load were correlated to intra-tumor variation of different immune cell populations.\nConclusion: Our study elucidates the mechanisms underlying enhancer dysregulation and deepens understanding of different tumorigenesis processes in distinct CCA subtypes, with potential significant therapeutics and clinical benefits.","abstract":"Objectives: Cholangiocarcinoma (CCA) is a heterogeneous malignancy with high mortality and dismal prognosis, and an urgent clinical need for new therapies. Knowledge of the CCA epigenome is largely limited to aberrant DNA methylation. Dysregulation of enhancer activities has been identified to affect carcinogenesis and leveraged for new therapies but is uninvestigated in CCA. Our aim is to identify potential therapeutic targets in different subtypes of CCA through enhancer profiling.\nDesign: Integrative multi-omics enhancer activity profiling of diverse CCA was performed. A panel of diverse CCA cell lines, patient-derived and cell line-derived xenografts were used to study identified enriched pathways and vulnerabilities. NanoString, multiplex immunohistochemistry staining and single-cell spatial transcriptomics were used to explore immunogenicity of diverse CCA.\nResults: We identified 3 distinct groups, associated with different etiologies and unique pathways. Drug inhibitors of identified pathways reduced tumor growth in in-vitro and in-vivo models. The first group (ESTRO), with mostly fluke-associated CCAs, displayed activation in estrogen signaling and were sensitive to MTOR inhibitors. Another group (OXPHO), with mostly BAP1 and IDH-mutant CCAs, displayed activated oxidative phosphorylation pathways, and were sensitive to oxidative phosphorylation inhibitors. Immune-related pathways were activated in the final group (IMMUN), made up of an immunogenic CCA subtype and CCA with aristolochic acid (AA) mutational signatures. Intra-tumor differences in AA mutation load were correlated to intra-tumor variation of different immune cell populations.\nConclusion: Our study elucidates the mechanisms underlying enhancer dysregulation and deepens understanding of different tumorigenesis processes in distinct CCA subtypes, with potential significant therapeutics and clinical benefits.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007599","title":"Granulocytes samples from myeloproliferative neoplasms","description":null,"abstract":"We have analyzed the clonal dynamics of non-driver genes in a cohort of 144 JAK2V617F mutated PV and ET patients receiving hydroxyurea (HU) therapy. Targeted next-generation sequencing was performed before HU treatment and at the timepoint of best molecular response JAK2V617F. The presence of non-driver mutations before initiating HU therapy was not associated with clinicohematological and molecular response as well as the clonal dynamics of non-driver mutations were not related to the evolution dynamics of JAK2V617F mutated PV and ET patients. However, an increase or appearance of progression-related mutations in DNA damage repair genes were observed during HU treatment.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007600","title":"Haplotyping project","description":"Haplotyping project","abstract":"Haplotyping project","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-05-06T12:05:47.724822+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007601","title":"PRADO trial - Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab plus nivolumab in stage III melanoma","description":"The PRADO trial tested a personalized response-directed treatment approach based on the pathologic response after neoadjuvant ipilimumab plus nivolumab in stage III melanoma patients. In patients achieving a major pathologic response, in their index lymph node (the largest lymph node metastasis at baseline), therapeutic lymph node dissection (TLND) and adjuvant therapy were omitted. Patients with partial response underwent TLND only, whereas patients with pathologic non-response underwent TLND and adjuvant systemic therapy ± synchronous radiotherapy.\nBiomarker analyses based on baseline RNA sequencing data were performed in order to find features that are associated with major pathologic response.","abstract":"The PRADO trial tested a personalized response-directed treatment approach based on the pathologic response after neoadjuvant ipilimumab plus nivolumab in stage III melanoma patients. In patients achieving a major pathologic response, in their index lymph node (the largest lymph node metastasis at baseline), therapeutic lymph node dissection (TLND) and adjuvant therapy were omitted. Patients with partial response underwent TLND only, whereas patients with pathologic non-response underwent TLND and adjuvant systemic therapy ± synchronous radiotherapy.\nBiomarker analyses based on baseline RNA sequencing data were performed in order to find features that are associated with major pathologic response.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-10-11T10:47:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007602","title":"Functional single-cell characterization of immune aplastic anemia shows convergence of NK and NK-like CD8+ T cells with disease-associated TCR signature","description":"Immune aplastic anemia (AA) is a life-threatening bone marrow (BM) failure disorder driven by an autoimmune T cell attack against the hematopoietic stem and progenitor cells (HSPCs). However, the autoantigen targets and the role of other immune cells are unknown. Here, by analyzing an international cohort of 156 AA patients with scRNA+TCRαβ-seq, TCRβ-seq, flow cytometry, and plasma cytokine profiling with comparisons to healthy controls and patients with other hematological disorders, we identify NK cells and CD8+ TEMRA cells expressing NK receptors with AA-associated TCRβ-seq motifs as the most dysregulated immune cell populations in AA BM. Functional co-culture experiments with scRNA-TCRαβ-seq readout utilizing primary HSPCs and immune cells provide evidence that NK cellscannot kill HSPCs alone, but sensitize them to CD8+ T cell-mediated killing. Furthermore, HSPCs induce strong activation of T cell clones with CD8+ TEMRA NK-like phenotype and AA-associated TCR motifs. Our results reveal the convergent evolution of innate and adaptive immune cells in AA, where NK cells support CD8+ T cell-mediated autoimmunity.","abstract":"Immune aplastic anemia (AA) is a life-threatening bone marrow (BM) failure disorder driven by an autoimmune T cell attack against the hematopoietic stem and progenitor cells (HSPCs). However, the autoantigen targets and the role of other immune cells are unknown. Here, by analyzing an international cohort of 156 AA patients with scRNA+TCRαβ-seq, TCRβ-seq, flow cytometry, and plasma cytokine profiling with comparisons to healthy controls and patients with other hematological disorders, we identify NK cells and CD8+ TEMRA cells expressing NK receptors with AA-associated TCRβ-seq motifs as the most dysregulated immune cell populations in AA BM. Functional co-culture experiments with scRNA-TCRαβ-seq readout utilizing primary HSPCs and immune cells provide evidence that NK cellscannot kill HSPCs alone, but sensitize them to CD8+ T cell-mediated killing. Furthermore, HSPCs induce strong activation of T cell clones with CD8+ TEMRA NK-like phenotype and AA-associated TCR motifs. Our results reveal the convergent evolution of innate and adaptive immune cells in AA, where NK cells support CD8+ T cell-mediated autoimmunity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-10-11T10:53:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007603","title":"HCA_Thymus_Organoid_ThyDesign_RNA","description":"Single cell RNA sequencing of cells from thymic organoids, which include differentiating human iPSCs and mouse stromal cells. There are many different T cell subsets which carry out different immune functions. Examples include cytotoxic CD8+ T cells that protect us against infection and cancer, and suppressive T regulatory cells (Tregs) that keep immune reactions under control. The power of T cells has been harnessed and widely applied in various fields of clinical medicine. Current examples include chimeric antigen receptor (CAR) T cells in cancer immunotherapy [1, 2]. At the same time, Tregs with their special suppressive function, have been used in autoimmune diseases and solid organ transplantation [3, 4] to try to establish tolerance. The thymus is a unique organ where T cells mature and develop into different lineages. Our lab has recently elucidated a comprehensive transcriptional network of T cell development by performing single-cell RNA-seq in human thymus across different developmental stages i.e. embryo, fetus, child, and adult (manuscript under revision at Science). We now have a good understanding of which transcription factors are involved in development of different T cell lineages in vivo. A recent paper from Montel-Hagen et al. [5] has built the most efficient in vitro system to date in order to generate mature T cells from stem cells including induced pluripotent stem cells (iPSCs) utilising an artificial thymic organoid system (ATO). The main output from this current ATO system is CD8 single positive T cells, with very few CD4 T cells and even fewer Tregs. We aim to induce expression of the key transcription factors identified from our human thymus sequencing study, to engineer T cell development towards Tregs in this in vitro system. Our end goal is to generate ‘off-the-shelf’ suppressive Tregs. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Single cell RNA sequencing of cells from thymic organoids, which include differentiating human iPSCs and mouse stromal cells. There are many different T cell subsets which carry out different immune functions. Examples include cytotoxic CD8+ T cells that protect us against infection and cancer, and suppressive T regulatory cells (Tregs) that keep immune reactions under control. The power of T cells has been harnessed and widely applied in various fields of clinical medicine. Current examples include chimeric antigen receptor (CAR) T cells in cancer immunotherapy [1, 2]. At the same time, Tregs with their special suppressive function, have been used in autoimmune diseases and solid organ transplantation [3, 4] to try to establish tolerance. The thymus is a unique organ where T cells mature and develop into different lineages. Our lab has recently elucidated a comprehensive transcriptional network of T cell development by performing single-cell RNA-seq in human thymus across different developmental stages i.e. embryo, fetus, child, and adult (manuscript under revision at Science). We now have a good understanding of which transcription factors are involved in development of different T cell lineages in vivo. A recent paper from Montel-Hagen et al. [5] has built the most efficient in vitro system to date in order to generate mature T cells from stem cells including induced pluripotent stem cells (iPSCs) utilising an artificial thymic organoid system (ATO). The main output from this current ATO system is CD8 single positive T cells, with very few CD4 T cells and even fewer Tregs. We aim to induce expression of the key transcription factors identified from our human thymus sequencing study, to engineer T cell development towards Tregs in this in vitro system. Our end goal is to generate ‘off-the-shelf’ suppressive Tregs. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007604","title":"Functional single-cell characterization of immune aplastic anemia shows convergence of NK and NK-like CD8+ T cells with disease-associated TCR signature","description":"Immune aplastic anemia (AA) is a life-threatening bone marrow (BM) failure disorder driven by an autoimmune T cell attack against the hematopoietic stem and progenitor cells (HSPCs). However, the autoantigen targets and the role of other immune cells are unknown. Here, by analyzing an international cohort of 156 AA patients with scRNA+TCRαβ-seq, TCRβ-seq, flow cytometry, and plasma cytokine profiling with comparisons to healthy controls and patients with other hematological disorders, we identify NK cells and CD8+ TEMRA cells expressing NK receptors with AA-associated TCRβ-seq motifs as the most dysregulated immune cell populations in AA BM. Functional co-culture experiments with scRNA-TCRαβ-seq readout utilizing primary HSPCs and immune cells provide evidence that NK cellscannot kill HSPCs alone, but sensitize them to CD8+ T cell-mediated killing. Furthermore, HSPCs induce strong activation of T cell clones with CD8+ TEMRA NK-like phenotype and AA-associated TCR motifs. Our results reveal the convergent evolution of innate and adaptive immune cells in AA, where NK cells support CD8+ T cell-mediated autoimmunity.","abstract":"Immune aplastic anemia (AA) is a life-threatening bone marrow (BM) failure disorder driven by an autoimmune T cell attack against the hematopoietic stem and progenitor cells (HSPCs). However, the autoantigen targets and the role of other immune cells are unknown. Here, by analyzing an international cohort of 156 AA patients with scRNA+TCRαβ-seq, TCRβ-seq, flow cytometry, and plasma cytokine profiling with comparisons to healthy controls and patients with other hematological disorders, we identify NK cells and CD8+ TEMRA cells expressing NK receptors with AA-associated TCRβ-seq motifs as the most dysregulated immune cell populations in AA BM. Functional co-culture experiments with scRNA-TCRαβ-seq readout utilizing primary HSPCs and immune cells provide evidence that NK cellscannot kill HSPCs alone, but sensitize them to CD8+ T cell-mediated killing. Furthermore, HSPCs induce strong activation of T cell clones with CD8+ TEMRA NK-like phenotype and AA-associated TCR motifs. Our results reveal the convergent evolution of innate and adaptive immune cells in AA, where NK cells support CD8+ T cell-mediated autoimmunity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-10-12T09:50:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007605","title":"Mammalian_genome_scramble","description":"The research project aims to introduce megabases of exogenous DNA into human cancer cell lines to transform our understanding of gene regulation and function. Using advanced genome engineering techniques, the team will insert large sequences containing entire regulatory networks into cells. This will allow for empirical testing of computational models predicting gene expression, chromatin accessibility, 3D genomic conformation, and gene essentiality. The data generated will refine these models, enhancing their predictive accuracy. The project has the potential to revolutionize personalized medicine, gene therapy, and our fundamental understanding of human genetics.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"The research project aims to introduce megabases of exogenous DNA into human cancer cell lines to transform our understanding of gene regulation and function. Using advanced genome engineering techniques, the team will insert large sequences containing entire regulatory networks into cells. This will allow for empirical testing of computational models predicting gene expression, chromatin accessibility, 3D genomic conformation, and gene essentiality. The data generated will refine these models, enhancing their predictive accuracy. The project has the potential to revolutionize personalized medicine, gene therapy, and our fundamental understanding of human genetics.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007606","title":"Somatic mutations associate with clonal expansion of CD8+ T cells","description":null,"abstract":"Somatic mutations in T cells can cause cancer but also have implications for immunological diseases and cell therapies. The mutation spectrum in non-malignant T cells is unclear. Here, we examined somatic mutations in CD4+ and CD8+ T cells from 90 patients with hematological and immunological disorders and used T cell receptor (TCR) and single-cell sequencing to link mutations with T cell expansions and phenotypes. CD8+ cells had higher mutation burden than CD4+ cells. Notably, the biggest variant allele frequency (VAF) of non-synonymous variants was higher than synonymous variants in CD8+ T cells, indicating non-random distribution. The non-synonymous VAF in CD8+ T cells strongly correlated with the TCR frequency, but not age. We identified mutated pathways essential for T cell function or recurrently mutated in lymphoid neoplasia. Single-cell sequencing revealed cytotoxic Temra phenotypes of mutated T cells. Our findings suggest that somatic mutations contribute to CD8+ T cell expansions without malignant transformation.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-10-12T12:15:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007607","title":"_HG__WC11110___Pilot_analyses_protein_domains_up_to_400nt_","description":"We have benchmarked using deep mutagenesis &gt;5 protein selection systems, finding the abundancePCA protein-fragment complementation system correlates best with reference in vitro stability measurements. A less well categorised tripartite sandwich assay has shown complementary results for protein stability. Through advancements in oligo synthesis longer domains can now be examined, we will use these two assays to generate stability information for a pilot of longer human protein domains that will feed future DMS design.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"The vast majority of variants on human protein-coding genes – including the most studied disease genes – are variants of uncertain significance, meaning that their phenotypic effects and their contribution to human disease are unknown. In order to carry out their functions, proteins need to fold into stable spatial conformations: their native structures. Accordingly, reduced protein fold stability or solubility is the most common mechanism by which missense mutations can lead to disease.\n\nRecently, deep learning algorithms methods have leveraged the large amounts of structural data for a wide range of proteins generated throughout decades of work in the structural biology community to accurately predict protein structure from sequence alone. This type of approach could be readily applied to many other traits of proteins; however, datasets of sufficient diversity and depth are lacking.\n\nIn order to begin to close this gap, one of our goals is to quantify the effects of mutations on the stability/folding of all intracellular human protein domains using massively scalable selection systems. The resulting data will serve as reference datasets for clinical variant interpretation, will allow the identification of disease mechanisms (quantifying the contribution of reduced protein stability as the disease mechanism for individual variants, genes and diseases), and will generate reference datasets to benchmark and train predictors of protein stability.\n\nIn the first stage of this project, we have targeted 1000 human small protein domains (&lt;85 aa) focusing on human disease genes. We have so far been using single mutant oligonucleotide libraries provided by BGI, and we expect this first stage of the project to be finished by summer 2023. Our goal is to extend this approach to an additional 1000 domains in order to cover all small (&lt;85 AA) protein domain families encoded in the human genome, with each domain family covered by at least 2 examples (and in a subset of cases, by many more examples per domain family).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007608","title":"Single_cell_RNA_Five_prime_profiling_of_PBMC_in_the_ELGH_cohort","description":"This data set contains 10x genomics single cell 5' profiling of PBMC from the blood donors participating in the East London Genes and Health (ELGH) study. Each individually tagged library contains 20,000 individual PBMC sourced from 10-13 individual donors that require deconvolution of to be analysed separately.     ","abstract":"The Cardinal project is a large scale single cell transcriptomics project analysing human PBMC's. The main aim of the study is to generate a reference data set of gene expression measurements in human immune cells that could be used in quantitative trait loci analysis (QTL). The study will be constructed from several thousand donors from both UK British and South Asia populations enabling the association of rare variants and non-European alleles with changes in gene expression levels in specific cell types. Participants within the study have been extensively phenotyped with genome wide association data sets being generated or available. Enabling the integration of genetic associated changes in gene expression with GWAS for traits and disease. This data set contains 10x genomics single cell 5' profiling of PBMC from the blood donors (n=&gt;100) participating in the Genes and Health  study. Each individually tagged library contains 20,000 individual PBMC sourced from 10-13 individual donors that require deconvolution of to be analysed separately.     ","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007609","title":"Shallow whole genome sequencing of FOCUS study","description":"Shallow whole genome sequencing of tumors from patients included in the FOCUS clinical trial. performed to calculate assocations of irinotecan with copy-number alterations.","abstract":"Shallow whole genome sequencing of tumors from patients included in the FOCUS clinical trial. performed to calculate assocations of irinotecan with copy-number alterations.","study_type":"Other","pubmed_ids":[17630037,25394515],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007610","title":"Omni-C data from Cornelia de Lange patients","description":null,"abstract":"Omni-C experiments with 2 control and 3 Cornelia De Lange patients to study the 3D genome organization defects. For each sample we have two biological replicates and to have enough coverage duplicate libraries were prepared for each sample.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007611","title":"A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1","description":"Tumor microtubes (TMs) connect glioma cells to a network with considerable relevance for tumor progression and therapy resistance. The determination of TM-interconnectivity in individual tumors has been challenging and the impact on patient survival unresolved. Here, a connectivity signature from single-cell RNA-sequenced (scRNA-Seq) xenografted primary glioblastoma (GB) cells has been established using a dye uptake methodology, confirmed with recording of cellular calcium epochs and validated with clinical correlations. Astrocyte-like and mesenchymal-like GB cells have the highest connectivity signature scores in scRNA-sequenced patient-derived xenografts and patient samples. In large GB cohorts, network connectivity correlated with the mesenchymal subtype and dismal patient survival. CHI3L1 has been identified and validated as a robust molecular marker of connectivity with functional relevance. The connectivity signature allows novel insights into brain tumor biology, provides a proof-of-principle that tumor cell TM-connectivity is relevant for patients’ prognosis, and serves as a robust prognostic biomarker.","abstract":"Tumor microtubes (TMs) connect glioma cells to a network with considerable relevance for tumor progression and therapy resistance. The determination of TM-interconnectivity in individual tumors has been challenging and the impact on patient survival unresolved. Here, a connectivity signature from single-cell RNA-sequenced (scRNA-Seq) xenografted primary glioblastoma (GB) cells has been established using a dye uptake methodology, confirmed with recording of cellular calcium epochs and validated with clinical correlations. Astrocyte-like and mesenchymal-like GB cells have the highest connectivity signature scores in scRNA-sequenced patient-derived xenografts and patient samples. In large GB cohorts, network connectivity correlated with the mesenchymal subtype and dismal patient survival. CHI3L1 has been identified and validated as a robust molecular marker of connectivity with functional relevance. The connectivity signature allows novel insights into brain tumor biology, provides a proof-of-principle that tumor cell TM-connectivity is relevant for patients’ prognosis, and serves as a robust prognostic biomarker.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-10-20T09:06:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007612","title":"Testing_genome_property_predictions__HiC_","description":"The research project aims to introduce megabases of exogenous DNA into human cancer cell lines to transform our understanding of gene regulation and function. Using advanced genome engineering techniques, the team will insert large sequences containing entire regulatory networks into cells. This will allow for empirical testing of computational models predicting gene expression, chromatin accessibility, 3D genomic conformation, and gene essentiality. The data generated will refine these models, enhancing their predictive accuracy. The project has the potential to revolutionize personalized medicine, gene therapy, and our fundamental understanding of human genetics.","abstract":"The research project aims to introduce megabases of exogenous DNA into human cancer cell lines to transform our understanding of gene regulation and function. Using advanced genome engineering techniques, the team will insert large sequences containing entire regulatory networks into cells. This will allow for empirical testing of computational models predicting gene expression, chromatin accessibility, 3D genomic conformation, and gene essentiality. The data generated will refine these models, enhancing their predictive accuracy. The project has the potential to revolutionize personalized medicine, gene therapy, and our fundamental understanding of human genetics.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007613","title":"Genome_Scramble__PromethION_","description":"The research project aims to introduce megabases of exogenous DNA into human cancer cell lines to transform our understanding of gene regulation and function. Using advanced genome engineering techniques, the team will insert large sequences containing entire regulatory networks into cells. This will allow for empirical testing of computational models predicting gene expression, chromatin accessibility, 3D genomic conformation, and gene essentiality. The data generated will refine these models, enhancing their predictive accuracy. The project has the potential to revolutionize personalized medicine, gene therapy, and our fundamental understanding of human genetics.","abstract":"The research project aims to introduce megabases of exogenous DNA into human cancer cell lines to transform our understanding of gene regulation and function. Using advanced genome engineering techniques, the team will insert large sequences containing entire regulatory networks into cells. This will allow for empirical testing of computational models predicting gene expression, chromatin accessibility, 3D genomic conformation, and gene essentiality. The data generated will refine these models, enhancing their predictive accuracy. The project has the potential to revolutionize personalized medicine, gene therapy, and our fundamental understanding of human genetics.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007614","title":"WES_sequencing_in_chemotherapy_samples","description":"We wish to sequence normal oesophageal epithelium from cancer patients who have undergone chemotherapy treatment to understand how the mutational landscape changes.","abstract":"We wish to sequence normal oesophageal epithelium from cancer patients who have undergone chemotherapy treatment to understand how the mutational landscape changes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007615","title":"TransplantLines Gut Microbiome study","description":"Kidney transplant recipients (KTR) have impaired health-related quality of life (HRQoL) and suffer from intestinal dysbiosis. Increasing evidence shows that gut health and HRQoL are tightly related in the general population. We investigate the association between the gut microbiome and HRQoL in KTR, using metagenomic sequencing data from fecal samples collected from 507 KTR.","abstract":"Kidney transplant recipients (KTR) have impaired health-related quality of life (HRQoL) and suffer from intestinal dysbiosis. Increasing evidence shows that gut health and HRQoL are tightly related in the general population. We investigate the association between the gut microbiome and HRQoL in KTR, using metagenomic sequencing data from fecal samples collected from 507 KTR.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007616","title":"GOSH_Childhood_Leukemia_Behjati_WellcomeCore_RNA","description":"Paediatric single-cell archival project\nThis project is taking sequential samples of children with B-cell acute lymphoblastic leukaemia (B-ALL) treated at Great Ormond Street Hospital (GOSH) between 2011 and the present day. Patients selected, are those that have done badly (e.g. had to escalate treatment, relapsed or died) despite having apparently \"\"good\"\" or \"\"intermediate\"\" risk cytogenetics, and often also had immunotherapy (e.g., the bi-specific T-cell engager blinatumomab) because of this. Using samples from key treatment-points, we hope to better characterise their disease and treatment response, to re-define understandings of risk for patients who did unexpectedly poorly. Additionally, we hope to define the disease/immunological factors that determine response to increasingly used immunotherapies within the field of paediatric B-ALL. \n\nEach of the samples will be viably frozen bone marrow-derived mononuclear cells. They will come in Eppendorf's, frozen and de-anonymised, from GOSH. We plan to primarily do single cell analysis (GEX, BCR +/-TCR), and then tumour-only WGS and bulk-RNA expression on left-over","abstract":"Paediatric single-cell archival project\nThis project is taking sequential samples of children with B-cell acute lymphoblastic leukaemia (B-ALL) treated at Great Ormond Street Hospital (GOSH) between 2011 and the present day. Patients selected, are those that have done badly (e.g. had to escalate treatment, relapsed or died) despite having apparently \"\"good\"\" or \"\"intermediate\"\" risk cytogenetics, and often also had immunotherapy (e.g., the bi-specific T-cell engager blinatumomab) because of this. Using samples from key treatment-points, we hope to better characterise their disease and treatment response, to re-define understandings of risk for patients who did unexpectedly poorly. Additionally, we hope to define the disease/immunological factors that determine response to increasingly used immunotherapies within the field of paediatric B-ALL. \n\nEach of the samples will be viably frozen bone marrow-derived mononuclear cells. They will come in Eppendorf's, frozen and de-anonymised, from GOSH. We plan to primarily do single cell analysis (GEX, BCR +/-TCR), and then tumour-only WGS and bulk-RNA expression on left-over","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-10-24T15:22:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007617","title":"GOSH_Childhood_Leukemia_Behjati_WellcomeCore_DNA","description":"Archival DNA project\nThis project aims to examine the genetic features of children with paediatric B-cell acute lymphoblastic leukaemia, treated on a historical trial (UKALLX, running from 1985-1990) who had reasonable survival rates, despite only receiving two out of the five treatment blocks they would receive today. Using extracted DNA from 350 children, the projects aims to utilise modern sequencing techniques to determine the genetic drivers of their leukaemia, and correlate this with their clinical outcomes. We hope to use this information to better identify which subtypes we can treatment-reduce, whilst maintaining treatment efficacy. \n\nEach of the samples are DNA extracted from the diagnostic bone marrow samples of patients. They are coming as extracted DNA in Eppendorf tubes from Great Ormond Street Hospital at fridge temperature (e.g. 4 degrees centigrade). Of note, as they were extracted many years ago, a proportion of the samples appear to have no liquid in them but will have lyophilised DNA that can be extracted.","abstract":"Archival DNA project\nThis project aims to examine the genetic features of children with paediatric B-cell acute lymphoblastic leukaemia, treated on a historical trial (UKALLX, running from 1985-1990) who had reasonable survival rates, despite only receiving two out of the five treatment blocks they would receive today. Using extracted DNA from 350 children, the projects aims to utilise modern sequencing techniques to determine the genetic drivers of their leukaemia, and correlate this with their clinical outcomes. We hope to use this information to better identify which subtypes we can treatment-reduce, whilst maintaining treatment efficacy. \n\nEach of the samples are DNA extracted from the diagnostic bone marrow samples of patients. They are coming as extracted DNA in Eppendorf tubes from Great Ormond Street Hospital at fridge temperature (e.g. 4 degrees centigrade). Of note, as they were extracted many years ago, a proportion of the samples appear to have no liquid in them but will have lyophilised DNA that can be extracted.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007618","title":"RNA sequencing of in vitro generated suppressive myeloid cells using parental and Sialidase expressing A549 cancer cell lines","description":null,"abstract":"Fresh peripheral blood mononuclear cells of four human donors were cultured together with either lung adenocarcinoma A549 cancer cells or A549-expressing H1N1 Sialidase cancer cells. These treatments induced the differentiation of donor cells into immunosuppressive MDSC-like cells, which were further subjected to bulk RNA sequencing. Computational analysis of RNA-Seq profiles of these cells was applied to understand the differences in their suppressive capacities.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-10-25T14:36:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007619","title":"High_resolution_multimodal_map_of_CD4__T_cell_activation_","description":"Naive and memory CD4+ T-cells will be isolated from the blood of 12 healthy individuals. A sample of blood from each donor will also be collected for genotyping.The cells will be stimulated with anti-CD3/anti-CD28/anti-CD2 and harvested at 12 time points of activation, including a resting sample. The 12 time points cover early (0h, 1h, 3h, 6h, 12h, 16h), middle (24h, 40h, 3 days) and late (4 days, 5 days, 5+ days) cell states of T cell activation. At each time point, donors will be pooled together before CITE-seq staining, sorted on viability and superloaded on a ChromiumX (180K cells loaded) for single-cell transcriptomics.","abstract":"T-cell activation is one of the fundamental processes underpinning immune response and is directed by highly dynamic processes with granular transcriptional, functional and morphological changes between cell types. This project constructs a high-resolution map of these processes during an activation time course in primary human naïve and memory CD4+ T-cells, capturing early (0h, 1h, 3h, 6h, 12h, 16h), middle (24h, 40h, 3 days) and late (4 days, 5 day and 5+ days) events across 12 donors. From the same population of cells, we will quantify single-cell transcriptomics and targeted surface proteome via 10X genomics, morphological features and biological processes (i.e: mitochondrial activity) via high-content imaging and secreted proteomics via Olink. The donors will also be genotyped to link the transcriptomic data to the other modalities.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007620","title":"Mutational_mapping_of_amyloid_fibril_formation__Mutagenesis_of_Amyloid_Protein_Sequences_","description":"The first goal of this project is to generate massive datasets that can feed machine learning algorithms to dissect the principles of amyloid formation and use these to design sequences where amyloid formation is specifically engineered or prevented. The second goal is to measure millions of interactions between mutations to build a model of the nucleating state for key amyloid sequences that cause human disease.","abstract":"The aggregation of proteins into insoluble fibrils is an unresolved phenomenon implicated in more than 40 incurable human diseases, including Alzheimer's disease and most types of dementia. To understand and accurately predict and modulate amyloid formation, here we plan to generate massive datasets that can feed machine learning algorithms to dissect the principles of amyloid formation and use these to design sequences where amyloid formation is specifically engineered or prevented. In addition, in order to provide the mechanistic  information needed to develop targeted approaches that prevent or slow down amyloif formatino, in this project we also plan to measure millions of interactions between mutations and use them to build a model of the nucleating state for key amyloid sequences that cause human disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007621","title":"HCA_Kidney_Adult_AZ_DNA_Managed_Access","description":"Investigation of tissue immunity in chronic kidney disease","abstract":"Chronic kidney disease (CKD) is characterized by failure and pathological remodeling of the kidney parenchyma in response to a variety of kidney pathologies. Tissue fibrosis and interstitial immune infiltrates are prominent histological features. In this study we aim to delineate the molecular signatures associated with pathological features of CKD and to compare these to healthy controls. By assaying kidneys across different disease stages, we will develop new insights into the development of pathological tissue remodeling. Using spatial transcriptomics, scRNAseq, and multiplexed imaging, we will build multidimensional models of the disease process, and nominate translationally significant pathways and targets.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007622","title":"HCA_Kidney_Adult_AZ_RNA_Managed_Access","description":"Investigation of tissue immunity in chronic kidney disease","abstract":"Chronic kidney disease (CKD) is characterized by failure and pathological remodeling of the kidney parenchyma in response to a variety of kidney pathologies. Tissue fibrosis and interstitial immune infiltrates are prominent histological features. In this study we aim to delineate the molecular signatures associated with pathological features of CKD and to compare these to healthy controls. By assaying kidneys across different disease stages, we will develop new insights into the development of pathological tissue remodeling. Using spatial transcriptomics, scRNAseq, and multiplexed imaging, we will build multidimensional models of the disease process, and nominate translationally significant pathways and targets.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-10-27T13:15:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007623","title":"HCA_Kidney_Adult_AZ_Spatial_Managed_Access","description":"Investigation of tissue immunity in chronic kidney disease","abstract":"Chronic kidney disease (CKD) is characterized by failure and pathological remodeling of the kidney parenchyma in response to a variety of kidney pathologies. Tissue fibrosis and interstitial immune infiltrates are prominent histological features. In this study we aim to delineate the molecular signatures associated with pathological features of CKD and to compare these to healthy controls. By assaying kidneys across different disease stages, we will develop new insights into the development of pathological tissue remodeling. Using spatial transcriptomics, scRNAseq, and multiplexed imaging, we will build multidimensional models of the disease process, and nominate translationally significant pathways and targets.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007624","title":"Identification of drug candidates targeting monocyte reprogramming in people living with HIV","description":null,"abstract":"We have previously illustrated in a cross-sectional cohort study that people living with HIV (PLHIV) are characterized by functional reprogramming of innate immune cells (van der Heijden et al., 2021a). In order to assess technical feasibility of omics technologies for application to larger cohorts, we compared bulk and single-cell transcriptomics as well as chromatin landscape analysis by ATAC-seq in a small number of blood samples derived from PLHIV and healthy controls from the 200-HIV cohort study. In particular, 1) single-cell RNA-seq analysis revealed that most immune cells in peripheral blood of PLHIV are altered in their transcriptomes, 2) that a specific functional monocyte state previously described in acute HIV infection is still existing in PLHIV while other monocyte cell states are only occurring in acute HIV, and 3) that a reverse transcriptome approach on a rather small number of PLHIV is sufficient to identify drug candidates for reversing the transcriptional phenotype of monocytes in PLHIV. These scientific findings and technological advancements for clinical application of single-cell transcriptomics form the basis for the larger 2000-HIV multicenter cohort study on PLHIV (Vos et al., 2022), for which a combination of bulk and single-cell transcriptomics will be included as the leading technology to determine disease endotypes in PLHIV and to predict disease trajectories and outcomes.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007625","title":"High_resolution_multimodal_map_of_CD4__T_cell_activation","description":"Naive and memory CD4+ T-cells will be isolated from the blood of 12 healthy individuals. The cells will be stimulated with anti-CD3/anti-CD28/anti-CD2 and harvested at 12 time points of activation, including a resting sample. The 12 time points cover early (0h, 1h, 3h, 6h, 12h, 16h), middle (24h, 40h, 3 days) and late (4 days, 5 days, 5+ days) cell states of T cell activation. At each time point, donors will be pooled together before CITE-seq staining, sorted on viability and superloaded on a ChromiumX (180K cells loaded) for single-cell transcriptomics. A sample of blood from each donor will also be collected for genotyping.","abstract":"T-cell activation is one of the fundamental processes underpinning immune response and is directed by highly dynamic processes with granular transcriptional, functional and morphological changes between cell types. This project constructs a high-resolution map of these processes during an activation time course in primary human naïve and memory CD4+ T-cells, capturing early (0h, 1h, 3h, 6h, 12h, 16h), middle (24h, 40h, 3 days) and late (4 days, 5 day and 5+ days) events across 12 donors. From the same population of cells, we will quantify single-cell transcriptomics and targeted surface proteome via 10X genomics, morphological features and biological processes (i.e: mitochondrial activity) via high-content imaging and secreted proteomics via Olink. The donors will also be genotyped to link the transcriptomic data to the other modalities.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007626","title":"EBNA2 ChIP-Re-ChIP in primary B-cells infected with EBV virus","description":null,"abstract":"EBNA2 ChIP-Re-ChIP in primary bulk B cells 4 days post EBV-infection with B95-8. DNA binding elements of the viral master regulator EBNA2, EBNA2-CBF transcription factor complex or EBNA2-EBF1 transcription factor complex were analyzed to identify virally targeted genes.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-04-16T10:07:00.025496+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007627","title":"Differential gene expression in the colon mucosa of irritable bowel syndrome patients with diarrhea-predominant symptoms.","description":null,"abstract":"The aim of this study is to characterize the pathophysiology of the irritable bowel syndrome (IBS) on the functional level and in parallel on the gene expression level. For this purpose RNAseq of mucosal biopsies was performed. The data from the differential expression analysis will be further processed by Ingenuity Pathway Analysis (IPA) software to gather Information on activated or inhibited signaling pathways in the disease.","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007628","title":"DERMATLAS__Leiomyosarcoma_WES","description":"irtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are leiomyosarcomas.","abstract":"irtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are leiomyosarcomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-10-31T10:04:03+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007629","title":"DERMATLAS__Leiomyoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are leiomyomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are leiomyomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-10-31T10:13:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007630","title":"DERMATLAS__Leiomyoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are leiomyomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are leiomyomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-10-31T10:22:26+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007631","title":"DERMATLAS__Leiomyosarcoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are leiomyosarcomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are leiomyosarcomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-10-31T10:27:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007632","title":"Targeted_NanoSeq_of_DNA_damage_associated_rare_diseases","description":"Genomic instability is a hallmark of ageing. Throughout life, both exogenous and endogenous mutational processes result in distinct damage to our DNA, consequently leading to increased genomic instability with age. Defects in the nucleotide excision repair (NER) pathway, which primarily responds to single-strand mutations, have been found to be associated with increased genome instability. However, they have also been shown to give rise to a number of premature ageing disorders, referred to as progeroid syndromes. Although the origin of these diseases is known, our knowledge about the course of disease is limited. In part, this can be explained by the short-life span of individuals suffering from premature ageing phenotypes, including but not limited to increased cancer risk, attenuated growth, cachexia or neurodegeneration. \n\nIn this study, we propose to investigate the contribution of somatic mutations and the clonal landscape to DNA damage accumulated in individuals with progeroid syndromes. We will assess the mutation and indel burden in a variety of individuals with alterations in genes such as ATM, FANCA, XPG, ERCC6L6, DNMT3B, ZBTB25, BRCA1, BLM or MSH2 as well as others. Although most of the syndromes show distinct ageing phenotypes, we will systematically analyse DNA extracted from peripheral blood mononuclear cells (PBMCs) and buccal epithelium. Extracted DNA will be utilised for targeted nanorate sequencing, a newly developed duplex sequencing protocol, which will enable us to accurately detect somatic mutations as well as small insertions and deletions (indels), mutational signatures and underlying processes of DNA damage. In addition, we will investigate the clonal landscape in progeroid syndromes. Overall, we anticipate the proposed study to improve our understanding of the role of somatic mutations in accelerated ageing phenotypes.","abstract":"Genomic instability is a hallmark of ageing. Throughout life, both exogenous and endogenous mutational processes result in distinct damage to our DNA, consequently leading to increased genomic instability with age. Defects in the nucleotide excision repair (NER) pathway, which primarily responds to single-strand mutations, have been found to be associated with increased genome instability. However, they have also been shown to give rise to a number of premature ageing disorders, referred to as progeroid syndromes. Although the origin of these diseases is known, our knowledge about the course of disease is limited. In part, this can be explained by the short-life span of individuals suffering from premature ageing phenotypes, including but not limited to increased cancer risk, attenuated growth, cachexia or neurodegeneration. \n\nIn this study, we propose to investigate the contribution of somatic mutations and the clonal landscape to DNA damage accumulated in individuals with progeroid syndromes. We will assess the mutation and indel burden in a variety of individuals with alterations in genes such as ATM, FANCA, XPG, ERCC6L6, DNMT3B, ZBTB25, BRCA1, BLM or MSH2 as well as others. Although most of the syndromes show distinct ageing phenotypes, we will systematically analyse DNA extracted from peripheral blood mononuclear cells (PBMCs) and buccal epithelium. Extracted DNA will be utilised for targeted nanorate sequencing, a newly developed duplex sequencing protocol, which will enable us to accurately detect somatic mutations as well as small insertions and deletions (indels), mutational signatures and underlying processes of DNA damage. In addition, we will investigate the clonal landscape in progeroid syndromes. Overall, we anticipate the proposed study to improve our understanding of the role of somatic mutations in accelerated ageing phenotypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007633","title":"VariantMedium: Sensitive and generalizable somatic point mutation calling with 3D DenseNets trained and evaluated on experimental confirmation data","description":"This study contains whole-exome sequencing (WES) and results of targeted deep-sequencing data of three matched tumor and normal cell lines, with two technical WES replicates each. The calls by Mutect2, Strelka2, and VariantMedium  were confirmed using targeted deep sequencing on Illumina Miseq The targeted deep sequencing was performed in three runs and the results are summarized under VCF files, with labels determined for point mutations and insertion-deletions.","abstract":"This study contains whole-exome sequencing (WES) and results of targeted deep-sequencing data of three matched tumor and normal cell lines, with two technical WES replicates each. The calls by Mutect2, Strelka2, and VariantMedium  were confirmed using targeted deep sequencing on Illumina Miseq The targeted deep sequencing was performed in three runs and the results are summarized under VCF files, with labels determined for point mutations and insertion-deletions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007634","title":"Targeted_NanoSeq_Airway_____exploring_the_influence_of_mutagens_on_the_genome_in_single_cell_derived_lung_colonies","description":"Targeted NanoSeq in polyclonal samples from patients and treated with a panel of mutegens (including vaping), as well as samples from re-exposing never-smoker clones to cigarette smoking extract for 3 months. The driver landscape across different experimental conditions will be compared.","abstract":"Investigating the influence of smoking related mutagens on the genome in single-cell derived lung colonies and polyclonal airway tissues. The aim of this study is to better understand the driver landscape and dynamics in airways under the selection pressure posed by different mutagens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007635","title":"snRNA-seq analysis in multinucleated myogenic FSHD cells identifies heterogeneous FSHD transcriptome signatures associated with embryonic-like program activation and oxidative stress-induced apoptosis","description":"The sporadic nature of DUX4 expression in FSHD muscle challenges comparative transcriptome analyses between FSHD and control samples. A variety of DUX4 and FSHD-associated transcriptional changes have been identified, but bulk RNA-seq strategies prohibit comprehensive analysis of their spatiotemporal relation, interdependence and role in the disease process. In this study, we used single-nucleus RNA-sequencing of nuclei isolated from patient- and control-derived multinucleated primary myotubes to investigate the cellular heterogeneity in FSHD. Taking advantage of the increased resolution in snRNA-sequencing of fully differentiated myotubes, two distinct populations of DUX4-affected nuclei could be defined by their transcriptional profiles. Our data provides insights into the differences between these two populations and suggests heterogeneity in two well-known FSHD-associated transcriptional aberrations: increased oxidative stress and inhibition of myogenic differentiation. Additionally, we provide evidence that DUX4-affected nuclei share transcriptome features with early embryonic cells beyond the well-described cleavage stage, progressing into the 8-cell and blastocyst stages. Altogether, our data suggests that the FSHD transcriptional profile is defined by a mixture of individual and sometimes mutually exclusive DUX4-induced responses and cellular state-dependent downstream effects.","abstract":"The sporadic nature of DUX4 expression in FSHD muscle challenges comparative transcriptome analyses between FSHD and control samples. A variety of DUX4 and FSHD-associated transcriptional changes have been identified, but bulk RNA-seq strategies prohibit comprehensive analysis of their spatiotemporal relation, interdependence and role in the disease process. In this study, we used single-nucleus RNA-sequencing of nuclei isolated from patient- and control-derived multinucleated primary myotubes to investigate the cellular heterogeneity in FSHD. Taking advantage of the increased resolution in snRNA-sequencing of fully differentiated myotubes, two distinct populations of DUX4-affected nuclei could be defined by their transcriptional profiles. Our data provides insights into the differences between these two populations and suggests heterogeneity in two well-known FSHD-associated transcriptional aberrations: increased oxidative stress and inhibition of myogenic differentiation. Additionally, we provide evidence that DUX4-affected nuclei share transcriptome features with early embryonic cells beyond the well-described cleavage stage, progressing into the 8-cell and blastocyst stages. Altogether, our data suggests that the FSHD transcriptional profile is defined by a mixture of individual and sometimes mutually exclusive DUX4-induced responses and cellular state-dependent downstream effects.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-02-06T11:28:45.373599+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007636","title":"COVID_19_Challenge_2_WOOE_RNA_Managed_Access","description":"Single-cell profiling of healthy adult volunteers that were inoculated with SARS-CoV-2.","abstract":"Single-cell profiling of seronegative and seropositive humans that were inoculated with SARS-CoV-2. The cellular response during SARS-CoV-2 infection is profiled using single-cell transcriptomics, CITE-seq and single cell adaptive immune receptor (TCR) profiling by sampling PBMCs and nasal swabs before and at multiple time points during SARS-CoV-2 infection. This one-of-a-kind cellular map will give unique temporal resolution of how nasal and circulating immune cells respond to SARS-CoV-2 exposure and infection.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-11-08T10:27:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007637","title":"MLL_leukemia_clonal_origin___bulk","description":"In order to study the clonal origin of MLL-rearranged childhood leukemia, we perform whole genome sequencing of single-cell-derived colonies of both normal and leukemic CD34+ cells in multiple patients. The primary question is the timing of: 1) the MLL translocation; 2) the leukemic expansion. To some extent and given certain assumptions this can be answered by sequencing only the leukemic cells and quantifying the number of shared mutations. Sequencing of normal HSPCs will gain additional insights. First, it will allow us to time the leukemic expansion in terms of divergence from the normal phylogenetic tree, providing an estimate less dependent on the number of shared mutations across leukemic cells. Second, it could provide additional timing markers, if used in conjunction with other data sources such as buccal swab DNA sequencing (gastrulation marker) and RNAseq data (in the case of females, X-inactivation timing). Third, comparison with the normal HSPC phylogenetic tree may show that the leukemia develops from an already expanded “normal” clade.  Here, we perform whole genome sequencing of bulk leukemia samples.","abstract":"In order to study the clonal origin of MLL-rearranged childhood leukemia, we perform whole genome sequencing of single-cell-derived colonies of both normal and leukemic CD34+ cells in multiple patients. The primary question is the timing of: 1) the MLL translocation; 2) the leukemic expansion. Sequencing of leukemic cells and normal HSPCs will allow us to time the leukemic expansion in terms of divergence from the normal phylogenetic tree and trace the fetal origins of MLL-rearranged leukemia.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007638","title":"Crosstalk of iFibro and FOLR2+ macrophages in CKD","description":"Crosstalk of iFibro and FOLR2+ macrophages in CKD","abstract":"Crosstalk of iFibro and FOLR2+ macrophages in CKD","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007639","title":"Clinical validity of post-surgery circulating tumor DNA testing in stage III colon cancer patients treated  with adjuvant chemotherapy: the PROVENC3 study","description":"This study assessed the clinical validity of post-surgery ctDNA detection in patients with stage III CRC treated with ACT. Blood was collected pre-surgery, post-surgery and post-ACT for 210 patients. Tumor-informed detection of ctDNA was performed through integrated whole genome sequencing (WGS) analyses of formalin-fixed paraffin-embedded tumor tissue DNA (80x), germline PBMC DNA (40x), and plasma cell-free DNA (30x). Liquid biopsy results show a worse TTR for ctDNA-positive compared to ctDNA-negative patients (HR: 6.1, [95%CI: 3.3-10.8], P&lt;0.001), with 38% of patients that ultimately experienced a recurrence being ctDNA-positive post-surgery. In conclusion, post-surgery ctDNA detection by tumor-informed WGS is a strong prognostic biomarker in stage III colon cancer patients.","abstract":"This study assessed the clinical validity of post-surgery ctDNA detection in patients with stage III CRC treated with ACT. Blood was collected pre-surgery, post-surgery and post-ACT for 210 patients. Tumor-informed detection of ctDNA was performed through integrated whole genome sequencing (WGS) analyses of formalin-fixed paraffin-embedded tumor tissue DNA (80x), germline PBMC DNA (40x), and plasma cell-free DNA (30x). Liquid biopsy results show a worse TTR for ctDNA-positive compared to ctDNA-negative patients (HR: 6.1, [95%CI: 3.3-10.8], P&lt;0.001), with 38% of patients that ultimately experienced a recurrence being ctDNA-positive post-surgery. In conclusion, post-surgery ctDNA detection by tumor-informed WGS is a strong prognostic biomarker in stage III colon cancer patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007640","title":"Birth_Cohort_ALSPAC","description":"Wellcome Sanger Institute (WSI) proposes to exome sequence approximately 34,500 individuals from the ALSPAC, Born in Bradford (BiB) and Fenland cohorts. This proposal will supplement WSI core-funding from the Wellcome Trust to enable comprehensive sequencing of the ALSPAC and BiB cohorts. This proposal builds upon exome sequencing of subsets of the ALSPAC and BiB cohorts that has been conducted at WSI over the past 18 months.","abstract":"The ALSPAC and BiB datasets are world-leading cohorts with respect to multi-dimensional longitudinal assessment of child development, and as such they complement existing UK adult cohort data assets such as the UKBiobank exome and genome sequencing data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-11-14T12:38:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007641","title":"A dysfunctional T cell gene signature for predicting non-response to PD-1 blockade in non-small cell lung cancer that is suitable for routine clinical diagnostics","description":"Since PD-1 blockade is only effective in a minority of patients with advanced stage NSCLC, biomarkers are needed to guide treatment decisions. Tumor infiltration by PD-1T TILs, a dysfunctional tumor-infiltrating lymphocyte (TIL) pool with tumor-reactive capacity, can be detected by digital quantitative IHC and has been established as a novel predictive biomarker in NSCLC. To facilitate translation of this biomarker to the clinic, we here aimed to develop a robust RNA signature reflecting a tumor’s PD-1T TIL status.,mRNA expression analysis using Nanostring was performed in baseline tumor samples from 41 advanced stage NSCLC patients treated with nivolumab that were selected based on PD-1T TIL infiltration by IHC. Samples were included as training cohort (n=41) to develop a predictive gene signature. This signature was independently validated in a second cohort (n=42). Primary outcome was disease control at 12 months (DC 12m) and secondary outcome was progression-free and overall survival. ,Regularized regression analysis yielded a signature using 12 out of 56 differentially expressed genes between PD-1T IHC high tumors from patients with DC 12m and PD-1T IHC low tumors from patients with progressive disease (PD). In the validation cohort 6/6 (100%) patients with DC 12m and 23/36 (64%) with PD were correctly classified with an NPV of 100% and a PPV of 32%.,The PD-1T mRNA signature showed a similar high sensitivity and high NPV as the digital IHC quantification of PD-1T TILs. This provides a straightforward approach allowing for easy implementation in a routine diagnostic clinical setting.","abstract":"Since PD-1 blockade is only effective in a minority of patients with advanced stage NSCLC, biomarkers are needed to guide treatment decisions. Tumor infiltration by PD-1T TILs, a dysfunctional tumor-infiltrating lymphocyte (TIL) pool with tumor-reactive capacity, can be detected by digital quantitative IHC and has been established as a novel predictive biomarker in NSCLC. To facilitate translation of this biomarker to the clinic, we here aimed to develop a robust RNA signature reflecting a tumor’s PD-1T TIL status.,mRNA expression analysis using Nanostring was performed in baseline tumor samples from 41 advanced stage NSCLC patients treated with nivolumab that were selected based on PD-1T TIL infiltration by IHC. Samples were included as training cohort (n=41) to develop a predictive gene signature. This signature was independently validated in a second cohort (n=42). Primary outcome was disease control at 12 months (DC 12m) and secondary outcome was progression-free and overall survival. ,Regularized regression analysis yielded a signature using 12 out of 56 differentially expressed genes between PD-1T IHC high tumors from patients with DC 12m and PD-1T IHC low tumors from patients with progressive disease (PD). In the validation cohort 6/6 (100%) patients with DC 12m and 23/36 (64%) with PD were correctly classified with an NPV of 100% and a PPV of 32%.,The PD-1T mRNA signature showed a similar high sensitivity and high NPV as the digital IHC quantification of PD-1T TILs. This provides a straightforward approach allowing for easy implementation in a routine diagnostic clinical setting.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007642","title":"Exome_NanoSeq___Bladder","description":"Exome NanoSeq in bladders from a number of donors, including donors with and without malignancy. Samples may contain pre-malignant histology.","abstract":"Investigating the driver landscape across a large number of bladder specimens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007643","title":"Exome_NanoSeq___Breast","description":"Exome NanoSeq in breast tissue from a number of donors.","abstract":"Investigating the driver landscape across a large number of breast specimens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007644","title":"Exome_NanoSeq___Stomach","description":"Exome NanoSeq in stomach samples from a number of donors, including donors with and without malignancy. Samples may contain pre-malignant histology.","abstract":"Investigating the driver landscape across a large number of stomach specimens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007645","title":"Exome_NanoSeq___Endometrium","description":"Exome NanoSeq on endometrial samples from a number of donors. Samples may contain pre-malignant histology.","abstract":"Investigating the driver landscape in the normal endometrium","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007646","title":"Targeted_NanoSeq___Adrenal","description":"Targeted NanoSeq in adrenal glands from a number of donors, both healthy and with pathology.","abstract":"Investigating the driver landscape in adrenals, in both health and disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007647","title":"Targeted_NanoSeq___Thyroid","description":"Targeted NanoSeq in thyroid from a number of donors, both healthy and with pathology.","abstract":"Investigating the driver landscape in thyroid, in both health and disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-11-16T14:19:41+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007648","title":"Isogut__Isoform_usage_in_healthy_and_Crohn_s_disease_gut_biopsies_using_long_read_single_cell_sequencing","description":"In this project, our first aim will be to understand the cell-type and of gene isoforms in the gut. Secondly, we aim to establish the role of these isoforms in health and Crohn’s disease gut biopsies.Third, we are interested in lowly-used isoforms. Addressing these three aims will provide evidence that understanding alternative splicing regulation is core to understanding gene expression regulation and disease-associated genetic variation in the context of complex diseases. \nOur proposal is to use unfragmented cDNA from gut biopsies that were previously dissociated into single cells using an established tissue dissociation protocol and the 10X Genomics single-cell 3’ GEM kit to perform single-cell long-read RNA-seq as part of the terminal ileum atlas project. After obtaining unfragmented cDNA, our protocol will bifurcate from the terminal ileum project at the library preparation step. Specifically, we will use the MAS-seq kit from Pacbio (PN: 102-659-600), which concatenates 16 cDNA molecules in a single array of 12-14 kbp. The resulting arrays will then be sequenced on the Revio sequencer from Pacbio. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Single-cell long-read sequencing enables an unprecedented look into the isoform landscape of single-cells. Previous work in our lab (MacroMap) has shown the relevance of genetic variation that underpins alternative splicing in complex diseases. With the newly-developed library preparation kit from Pacbio (MAS-seq), high-throughput single-cell long-read sequencing has become feasible. Our project aims are three-fold:\n1-Establishing a single-cell isoform atlas for the healthy gut. Currently, the gene expression atlas is being built by our group and others, but an isoform atlas for the gut is still lacking and technically challenging with short-read single-cell data. We will use 8 healthy gut samples for this purpose.\n2-Profiling the differential isoform usage landscape between 8 healthy and 8 Crohn’s disease gut biopsies. This will identify a set of potentially pathological isoforms in their relevant cellular context.\n3- Our previous work also showed the particular relevance of lowly-used isoforms in immune-disease genetics. Using one SMRT cell per sample (&gt;110 million full-length reads per sample in Pacbio’s runs), we will have enough coverage to uncover lowly-used and potentially previously unannotated isoforms","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007649","title":"Analysis of monochorionic dizygotic twin chimera","description":"Single-cell RNA-sequencing of peripheral blood mononuclear cells of monochorionic dizygotic twins were used to understand the composition of their blood cells. In addition, single-cell isolated buccal epithelial cells were subjected to low-input whole-genome sequencing.","abstract":"Single-cell RNA-sequencing of peripheral blood mononuclear cells of monochorionic dizygotic twins were used to understand the composition of their blood cells. In addition, single-cell isolated buccal epithelial cells were subjected to low-input whole-genome sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007650","title":"Early evolutionary branching across spatial domains predisposes to clonal replacement under chemotherapy in neuroblastoma","description":"Neuroblastoma (NB) is one of the most lethal childhood cancers due its propensity to treatment resistance. By spatial mapping of subclone geographies before and after chemotherapy across 89 tumor regions from 12 NBs, we find that densely packed territories of closely related subclones present at diagnosis are replaced under effective treatment by islands of distantly related survivor subclones, originating from a different most recent ancestor compared to lineages dominating before treatment. Conversely, in tumors that progressed under treatment, ancestors of subclones dominating later in disease are present already at diagnosis. Chemotherapy treated xenografts and cell culture models replicates these two contrasting scenarios and shows branching evolution to be a constant feature of proliferating NB cells. Phylogenies based on whole genome sequencing of 505 individual NB cells indicate that a rich repertoire of parallel subclones, emerges already with the first oncogenic mutations and lays the foundation for clonal replacement under treatment.","abstract":"Neuroblastoma (NB) is one of the most lethal childhood cancers due its propensity to treatment resistance. By spatial mapping of subclone geographies before and after chemotherapy across 89 tumor regions from 12 NBs, we find that densely packed territories of closely related subclones present at diagnosis are replaced under effective treatment by islands of distantly related survivor subclones, originating from a different most recent ancestor compared to lineages dominating before treatment. Conversely, in tumors that progressed under treatment, ancestors of subclones dominating later in disease are present already at diagnosis. Chemotherapy treated xenografts and cell culture models replicates these two contrasting scenarios and shows branching evolution to be a constant feature of proliferating NB cells. Phylogenies based on whole genome sequencing of 505 individual NB cells indicate that a rich repertoire of parallel subclones, emerges already with the first oncogenic mutations and lays the foundation for clonal replacement under treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-11-21T10:23:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007651","title":"BRCA1_methylation_timing_LCM_WGS","description":"BRCA1 promoter methylation can predispose to the development of aggressive cancers of the breast by causing homologous recombination deficiency(HRD). Emerging evidence reveals that methylation of the BRCA1 promoter can sometimes be detected at low levels in blood samples and this seems to be predictive of future future breast cancer diagnosis.  It is currently unknown why and when this event might occur during the individuals lifetime,  yet establishing this will be important for developing screening interventions.","abstract":"In this study  individuals with breast cancer were screened for detectable BRCA1 methylation in a blood draw and in their breast tumour (affecting the same same allele). From eligible individuals, single cell derived colonies (5,000-10,000 cells) were derived from lymphocytes from a peripheral blood draw (fresh citrate) grown for 14 days. DNA was extracted from each colony (Picopure) and BRCA1 methylation status determined. Where a subset of colonies were confirmed to have BRCA1 methylation all of these colonies and a control set (upto ~100) non methylated colonies were selected for combined EM-seq and WGS sequencing. \n\nThe genome wide methylation and genomic data will be used to infer the evolutionary timing of the BRCA1 methylation event in addition to any potential associated events.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007652","title":"BRCA1_methylation_timing_EMseq","description":"BRCA1 promoter methylation can predispose to the development of aggressive cancers of the breast by causing homologous recombination deficiency(HRD). Emerging evidence reveals that methylation of the BRCA1 promoter can sometimes be detected at low levels in blood samples and this seems to be predictive of future future breast cancer diagnosis.  It is currently unknown why and when this event might occur during the individuals lifetime,  yet establishing this will be important for developing screening interventions.","abstract":"In this study  individuals with breast cancer were screened for detectable BRCA1 methylation in a blood draw and in their breast tumour (affecting the same same allele). From eligible individuals, single cell derived colonies (5,000-10,000 cells) were derived from lymphocytes from a peripheral blood draw (fresh citrate) grown for 14 days. DNA was extracted from each colony (Picopure) and BRCA1 methylation status determined. Where a subset of colonies were confirmed to have BRCA1 methylation all of these colonies and a control set (upto ~100) non methylated colonies were selected for combined EM-seq and WGS sequencing. \n\nThe genome wide methylation and genomic data will be used to infer the evolutionary timing of the BRCA1 methylation event in addition to any potential associated events.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007653","title":"Lymphoma_WGS","description":"The somatic mutational landscape of lymphoma will be characterized using LCMB-WGS.","abstract":"The somatic mutational landscape of lymphoma will be characterized using LCMB-WGS","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-11-22T13:13:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007654","title":"DERMATLAS__Myoepithelioma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are: myoepithelioma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are: myoepithelioma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007655","title":"DERMATLAS__Myoepithelioma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are: myoepithelioma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are: myoepithelioma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007656","title":"Exome_nanoseq_paediatric_autopsy","description":"Exome NanoSeq across a range of tissues taken at autopsy from patients with lethal paediatric brain tumours.","abstract":"Investigating the driver landscape in the background normal tissues of patients with brain tumours.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007657","title":"Mapping_genetic_variants_underlying_gene_regulation_in_healthy_intestinal_cell_types_to_identify_novel_IBD_drug_targets","description":"We are generating single cell data (10X Genomics and Illumina) to investigate the transcriptome and epigenomic data quality of nuclei isolated from gut tissue. We have developed several nuclei isolation protocols from fresh and cryopreserved tissue samples and prepared snRNAseq from these experiments. These results will inform us which nuclei isolation protocol and tissue input are perfoming best to be implement it on our main project to study transcriptome and epigenomic landscape on gut tissue on healthy and Crohn's disease patients.\nThe results will help us to optimize our workflow for sample processing in larger numbers per batch, thereby reducing batch and processing bias variation while lowering our current cost per sample for scRNAseq data. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"We are generating single cell data to investigate the transcriptome and epigenomic data quality of nuclei isolated from gut tissue obtained by several protocols from fresh and cryostored gut biopsy samples.\nThe outcome from these experiments will inform us which nuclei isolation protocol and tissue input are perfoming best single cell transcriptome data. Furthermore, will also help us to optimize our workflow for sample processing in batches to avoid bias effect between samples and to investigate integration methods for transcriptomic and epigenomic data generated from the same tissue.\nThe chosen protocol will be implement on our main project to study transcriptome and epigenomic landscape on gut tissue on healthy and Crohn's disease patients which include a larger cohort of samples.","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007658","title":"Buccal Sample Methylation for Breast Cancer Detection","description":"This study encompasses buccal sample DNA methylation (IlluminaMethylationEPIC array) from breast cancer cases and healthy age-matched controls.","abstract":"This study encompasses buccal sample DNA methylation (IlluminaMethylationEPIC array) from breast cancer cases and healthy age-matched controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-12-01T12:14:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007659","title":"JAGUAR__Mapping_the_impact_of_genetic_variation_on_immune_regulation_in_diverse_Latin_American_populations","description":"JAGUAR: mapping the impact of genetic variation on immune regulation in diverse Latin American populations Study description                                                                                                                                                                                The project JAGUAR creates a multimodal cell atlas of peripheral immune cells from individuals from across seven Latin American countries, reflecting the diverse ancestries within each country. By linking the gene and protein expression  with ancestry and rare coding variants information, we aim to explain how  they interact in creating healthy immune phenotypes.                                                                                                                                                           \nDataset title                                                                                                                                                                                        \nWhole genome sequencing and whole exome sequencing of healthy participants of the project Jaguar                  \nDataset description                                                                                                                                                                        \nWhole genome sequencing (shallow) and whole exome sequencing (deep) of 600 healthy participants of the project Jaguar.  Raw sequencing data as fastq files and genotyping data as VCF files.       \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Project JAGUAR focuses on building a comprehensive map of the impact of ancestral genetic diversity on the composition and regulation of the response of the immune system in seven LATAM populations. We are biobanking PBMC samples from 1080 individuals. Sampled groups within each country are balanced by sex and age, we also collect information about self-described ethnicity, health, environment and lifestyle. The currently funded activities will deliver a multimodal atlas of peripheral immune cells based on a representative twenty individuals per population (140 individuals in total), comprising 15% of the final JAGUAR cohort. LATAM individuals have a variable percentage of admixture, and self-reported ethnicity is unreliable. Therefore, we would like to make an informed decision for selecting the 20 individuals using genetic data. The blended exome-genomes data will enable more accurate inference of ancestry and rare coding variants, altogether providing much richer genetic information for these globally under-represented populations. The data will also be used for any downstream analysis, such as the interpretation of the multimodal single-cell datasets, sc-eQTL mapping.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007660","title":"Unraveling mutagenic processes influencing the tumor mutational patterns of individuals with Constitutional Mismatch Repair Deficiency","description":"Constitutional mismatch repair deficiency (CMMRD), caused by bi-allelic germline variants in one of the mismatch repair (MMR) genes, is a childhood cancer predisposition syndrome that often results in the development of multiple tumors early in life. A better understanding of mutational processes driving subsequent CMMRD tumors could advance optimal treatment. Therefore, we performed a genomic characterization of 41 tumors from 17 individuals with CMMRD. Mutational patterns in these tumors were found to be influenced by multiple factors, including the affected MMR genes, tumor types and somatic polymerase proofreading mutations. Temozolomide treatment left prominent mutational signatures in two second primary hematologic malignancies. Furthermore, a novel indel signature was found in 54% of the tumors, characterized by one base pair cytosine insertions in cytosine homopolymers. In conclusion, the analysis of sequential tumors in individuals with CMMRD reveals diverse mutational patterns influenced by the underlying mutated MMR gene, tumor type and treatment history.","abstract":"Constitutional mismatch repair deficiency (CMMRD), caused by bi-allelic germline variants in one of the mismatch repair (MMR) genes, is a childhood cancer predisposition syndrome that often results in the development of multiple tumors early in life. A better understanding of mutational processes driving subsequent CMMRD tumors could advance optimal treatment. Therefore, we performed a genomic characterization of 41 tumors from 17 individuals with CMMRD. Mutational patterns in these tumors were found to be influenced by multiple factors, including the affected MMR genes, tumor types and somatic polymerase proofreading mutations. Temozolomide treatment left prominent mutational signatures in two second primary hematologic malignancies. Furthermore, a novel indel signature was found in 54% of the tumors, characterized by one base pair cytosine insertions in cytosine homopolymers. In conclusion, the analysis of sequential tumors in individuals with CMMRD reveals diverse mutational patterns influenced by the underlying mutated MMR gene, tumor type and treatment history.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-12-05T12:59:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007661","title":"Targeted and shallow whole genome sequencing identifies therapeutic opportunities in p53abn endometrial cancers","description":"Purpose:\nShallow whole genome sequencing (sWGS) can detect copy number (CN) aberrations. In high-grade serous ovarian (HGSOC) sWGS identified CN signatures such as homologous recombination deficiency (HRD) to direct therapy. We applied sWGS with targeted sequencing to p53abn endometrial cancers (ECs) to identify additional prognostic stratification and therapeutic opportunities.\n\nExperimental Design:\nsWGS and targeted panel sequencing was performed on formalin-fixed paraffin-embedded p53abn ECs. CN alterations, mutational data and CN signatures were derived, and associations to clinicopathologic and outcomes data were assessed.\n\nResults:\nIn 187 p53abn ECs, 5 distinct CN signatures were identified. Signature 5 was associated with BRCA1/2 CN loss with features similar to HGSOC HRD signature. 22% potential HRD cases were identified, 35 patients with signature 5, and 8 patients with BRCA1/2 somatic mutations. Signatures 3 and 4 were associated with whole genome duplication, and CCNE1, ERBB2 and MYC amplifications, with mutations in PIK3CA enriched in signature 3. We observed improved overall survival (OS) for patients with signature 2 and worse OS for signatures 1 and 3. 28% of patients had CCNE1 amplification and this subset was enriched with carcinosarcoma histotype. 34% of patients, across all histotypes, had ERBB2 amplification and/or HER2 overexpression on immunohistochemistry, which was associated with worse outcomes. Mutations in PPP2R1A (29%) and FBXW7 (16%) were among the top 5 most common mutations.\n\nConclusions:\nsWGS and targeted sequencing identified therapeutic opportunities in 75% of p53abn EC patients. Further research is needed to determine the efficacy of treatments targeting these identified pathways within p53abn ECs.","abstract":"Purpose:\nShallow whole genome sequencing (sWGS) can detect copy number (CN) aberrations. In high-grade serous ovarian (HGSOC) sWGS identified CN signatures such as homologous recombination deficiency (HRD) to direct therapy. We applied sWGS with targeted sequencing to p53abn endometrial cancers (ECs) to identify additional prognostic stratification and therapeutic opportunities.\n\nExperimental Design:\nsWGS and targeted panel sequencing was performed on formalin-fixed paraffin-embedded p53abn ECs. CN alterations, mutational data and CN signatures were derived, and associations to clinicopathologic and outcomes data were assessed.\n\nResults:\nIn 187 p53abn ECs, 5 distinct CN signatures were identified. Signature 5 was associated with BRCA1/2 CN loss with features similar to HGSOC HRD signature. 22% potential HRD cases were identified, 35 patients with signature 5, and 8 patients with BRCA1/2 somatic mutations. Signatures 3 and 4 were associated with whole genome duplication, and CCNE1, ERBB2 and MYC amplifications, with mutations in PIK3CA enriched in signature 3. We observed improved overall survival (OS) for patients with signature 2 and worse OS for signatures 1 and 3. 28% of patients had CCNE1 amplification and this subset was enriched with carcinosarcoma histotype. 34% of patients, across all histotypes, had ERBB2 amplification and/or HER2 overexpression on immunohistochemistry, which was associated with worse outcomes. Mutations in PPP2R1A (29%) and FBXW7 (16%) were among the top 5 most common mutations.\n\nConclusions:\nsWGS and targeted sequencing identified therapeutic opportunities in 75% of p53abn EC patients. Further research is needed to determine the efficacy of treatments targeting these identified pathways within p53abn ECs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-12-05T19:49:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007662","title":"HCA_Heart_Adult_Wellcome_ONT_RNA_Managed_Access","description":"Long read single cell resolution RNA sequencing of human cardiac cells","abstract":"This is a beta test, applying Oxford Nanopore Technology sequencing on previously-generated 10X scRNAseq libraries. This will provide new insights into transcript isoform expression across the heart.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007663","title":"HCA_Heart_Foetal_Wellcome_ONT_RNA","description":"Long read single cell resolution RNA sequencing of human cardiac cells","abstract":"This is a beta test, applying Oxford Nanopore Technology sequencing on previously-generated 10X scRNAseq libraries. This will provide new insights into transcript isoform expression across the heart.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007664","title":"Stratton__WGS_FFPE_studies_HNC","description":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. \n\n\nThis pilot study will investigate opportunities for detecting mutational signatures in samples fixed in formalin and embedded in paraffin (FFPE) for variable lengths of time.","abstract":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. \n\nThis pilot study will investigate opportunities for detecting mutational signatures in samples fixed in formalin and embedded in paraffin (FFPE) for variable lengths of time.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007665","title":"HCA_Urogenital_Foetal_Clatworthy_RNA","description":"Characterizing developmental trajectories and immune composition of the urinary tract at single-cell resolution","abstract":"Through development, the fetal bladder and kidney become populated by immune populations originating in nascent haematopoietic organs. These cells reside alongside stromal and epithelial compartments of the tissue, and engage in complex niche interactions. In this project we will use single-cell RNA sequencing, single-cell ATAC sequencing, and spatial genomics methods to develop an integrated model for the spatio-temporal pattern of cell-cell interactions and gene expression programmes determining leukocyte tissue residence and function in the urinary tract during fetal development.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007666","title":"DNA-methylation variability in normal mucosa of patients with adenomatous polyps: a marker of field cancerization","description":"A study linking DNA methylation modifications in the normal mucosa of the right colon in individuals with adenomatous polyp formation","abstract":"Background: The phenomenon of field cancerization reflects the transition of normal cells into those predisposed to cancer. Assessing the scope and intensity of this process in the colon may support risk prediction and colorectal cancer prevention.\nMethods: The SWEPIC study, encompassing 1,111 participants for DNA methylation analysis and a subset of 84 for RNA-seq, was employed to detect field cancerization in individuals with adenomatous polyps (AP). Methylation variations were evaluated for their discriminative capability, including in external cohorts, genomic localization, clinical correlations, and associated RNA expression patterns.\nResults: Normal cecal tissue of individuals harboring an AP in the proximal colon manifested dysregulated DNA methylation compared to tissue from healthy individuals at 558 unique loci. Leveraging these adenoma-related differentially variable and methylated CpGs (aDVMCs), our classifier discerned between healthy and AP-adjacent tissues across SWEPIC datasets (cross-validated ROC AUC: [0.63-0.81]), including within age-stratified cohorts. This discriminative capacity was validated in three external sets, differentiating healthy from cancer-adjacent tissue (ROC AUC: [0.82-0.88]). Notably, aDVMC dysregulation correlated with polyp multiplicity. More than 50% of aDVMCs were significantly associated with age. These aDVMCs were enriched in active regions of the genome (p under 0.001) and associated genes exhibited altered expression in AP-adjacent tissues.\nConclusions: Our findings underscore the early onset of field cancerization in the right colon during the neoplastic transformation process. A more extensive validation of aDVMC dysregulation as a stratification tool could pave the way for enhanced surveillance approaches, especially given its linkage to adenoma emergence.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2023-12-08T12:57:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007667","title":"HCA_Skin_Disease_Atopic_Dermatitis_Wellcome_RNA_Managed_Access","description":"Defining the spatial transcriptome and cell-cell interactions in atopic dermatitis skin","abstract":"Atopic eczema (eczema) is the most common inflammatory skin disease, with a lifetime prevalence of 10-15% and the leading cause of disease burden conferred by skin disease. Eczema drugs targeting Th2 immune mediators have recently been approved, including the biologic Dupilumab and Janus Kinase (JAK) inhibitors. However, the response is highly heterogeneous, meaning patients often cycle through multiple drugs for disease control. Understanding the molecular drivers of treatment response is necessary to shift from trial-and-error to data-driven drug allocation, to optimise efficacy, reduce time to remission, avoid treatment switches, drug-related morbidity and improve cost effectiveness. The BEACON eczema drug trial will be the largest platform trial worldwide to directly compare the effectiveness and tolerability of standard and targeted eczema drugs. The mechanistic BEACON-omics study will utilise longitudinal single-cell multiomics and spatial genomics skin profiling of samples collected from carefully phenotyped patients (using gold standard clinical outcomes) of responders and non-responders from each of the BEACON treatment arms (dupilumab, JAK1 inhibitor and methotrexate) to identify novel mechanisms of drug action in these patients, which will inform drug innovation efforts and pave the way for future target discovery.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007668","title":"HCA_Skin_Disease_Atopic_Dermatitis_Wellcome_Spatial_Managed_Access","description":"Defining the spatial transcriptome and cell-cell interactions in atopic dermatitis skin","abstract":"Atopic eczema (eczema) is the most common inflammatory skin disease, with a lifetime prevalence of 10-15% and the leading cause of disease burden conferred by skin disease. Eczema drugs targeting Th2 immune mediators have recently been approved, including the biologic Dupilumab and Janus Kinase (JAK) inhibitors. However, the response is highly heterogeneous, meaning patients often cycle through multiple drugs for disease control. Understanding the molecular drivers of treatment response is necessary to shift from trial-and-error to data-driven drug allocation, to optimise efficacy, reduce time to remission, avoid treatment switches, drug-related morbidity and improve cost effectiveness. The BEACON eczema drug trial will be the largest platform trial worldwide to directly compare the effectiveness and tolerability of standard and targeted eczema drugs. The mechanistic BEACON-omics study will utilise longitudinal single-cell multiomics and spatial genomics skin profiling of samples collected from carefully phenotyped patients (using gold standard clinical outcomes) of responders and non-responders from each of the BEACON treatment arms (dupilumab, JAK1 inhibitor and methotrexate) to identify novel mechanisms of drug action in these patients, which will inform drug innovation efforts and pave the way for future target discovery.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007669","title":"HCA_Blood_Disease_Atopic_Dermatitis_Wellcome_RNA_Managed_Access","description":"Defining the spatial transcriptome and cell-cell interactions in atopic dermatitis skin","abstract":"Atopic eczema (eczema) is the most common inflammatory skin disease, with a lifetime prevalence of 10-15% and the leading cause of disease burden conferred by skin disease. Eczema drugs targeting Th2 immune mediators have recently been approved, including the biologic Dupilumab and Janus Kinase (JAK) inhibitors. However, the response is highly heterogeneous, meaning patients often cycle through multiple drugs for disease control. Understanding the molecular drivers of treatment response is necessary to shift from trial-and-error to data-driven drug allocation, to optimise efficacy, reduce time to remission, avoid treatment switches, drug-related morbidity and improve cost effectiveness. The BEACON eczema drug trial will be the largest platform trial worldwide to directly compare the effectiveness and tolerability of standard and targeted eczema drugs. The mechanistic BEACON-omics study will utilise longitudinal single-cell multiomics and spatial genomics skin profiling of samples collected from carefully phenotyped patients (using gold standard clinical outcomes) of responders and non-responders from each of the BEACON treatment arms (dupilumab, JAK1 inhibitor and methotrexate) to identify novel mechanisms of drug action in these patients, which will inform drug innovation efforts and pave the way for future target discovery.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007670","title":"HCA_Thymus_Foetal_Thydesign_RNA","description":"T cells are central to adaptive immunity and thus crucial for understanding and treating human disease. While extensively studied in model organisms, translating this knowledge to humans can sometimes be limited by their rapid cross-species evolution and diverse","abstract":"This study aims to address this gap by studying GRNs directly in the human thymus. To this end, we will apply single nuclei multiomic profiling (10x multiome, scRNA+scATAC) to study thymic cells from the foetal and paediatric human thymus.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007671","title":"DERMATLAS__Cutaneous_gd_T_cell_lymphoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Cutaneous gd T-cell lymphoma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\nThe cases in this cohort are Cutaneous gd T-cell lymphoma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007672","title":"HCA_Skin_Adult_BSTOP_Haniffa_RNA_Managed_Access","description":"Defining the immune landscape of inflammatory disease using multi-omics approaches","abstract":"The introduction of biologic therapies has transformed outcomes for people with psoriasis over recent years. However, despite apparent clinical resolution on treatment, psoriasis will inevitably recur following drug withdrawal, commonly at previously lesional sites. A better understanding of the key cell types and their interactions involved in resolved and recurring skin may reveal the events leading to the shift from resolved skin to recurrence. High-resolution single-cell gene expression and ATAC sequencing may help to realize this goal, ultimately informing novel strategies for future clinical practice.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007673","title":"HCA_Skin_Adult_BSTOP_Haniffa_Spatial_Managed_Access","description":"Defining the immune landscape of inflammatory disease using multi-omics approaches","abstract":"The introduction of biologic therapies has transformed outcomes for people with psoriasis over recent years. However, despite apparent clinical resolution on treatment, psoriasis will inevitably recur following drug withdrawal, commonly at previously lesional sites. A better understanding of the key cell types and their interactions involved in resolved and recurring skin may reveal the events leading to the shift from resolved skin to recurrence. High-resolution single-cell gene expression and ATAC sequencing may help to realize this goal, ultimately informing novel strategies for future clinical practice.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007674","title":"Mitochondrial DNA mosaicism in human somatic cells","description":"Genomic alterations accumulate in the somatic cells throughout an individual’s lifetime. Recent sequencing studies have documented widespread mutations in the nuclear genome and the frequent clonal competition of normal cells carrying mutations. However, the landscape of mitochondrial DNA (mtDNA) heteroplasmy in normal human tissues is poorly understood. In this study, we investigated the whole genome sequences (WGSs) of 2,096 clones established from non-neoplastic healthy single cells obtained from 31 donors. In addition, we analyzed 31 WGSs of neoplastic cells, including 12 clones established from adenomatous polyps from one individual with MUTYH-associated polyposis and 19 matched colorectal carcinomas from individuals who donated normal colorectal clones.","abstract":"Genomic alterations accumulate in the somatic cells throughout an individual’s lifetime. Recent sequencing studies have documented widespread mutations in the nuclear genome and the frequent clonal competition of normal cells carrying mutations. However, the landscape of mitochondrial DNA (mtDNA) heteroplasmy in normal human tissues is poorly understood. In this study, we investigated the whole genome sequences (WGSs) of 2,096 clones established from non-neoplastic healthy single cells obtained from 31 donors. In addition, we analyzed 31 WGSs of neoplastic cells, including 12 clones established from adenomatous polyps from one individual with MUTYH-associated polyposis and 19 matched colorectal carcinomas from individuals who donated normal colorectal clones.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007675","title":"Community efforts can form the ground to unravel complex biology of the human neuronal landscape to understand neurodegeneration","description":"Precise determination of cellular identity and molecular phenotypes through advanced high-throughput technologies is crucial for understanding intricate tissue functions, especially in complex organs like the brain. This becomes pivotal for a comprehensive mapping of cell identities throughout the human brain to unravel its function. In this study, we present findings from a multi-center investigation involving seven genome centers. We analyzed single-nucleus transcriptomes obtained from NeuN+ neurons from the putamen and caudate nucleus of both healthy individuals and Parkinson's Disease (PD) patients. Our results demonstrate the potential for establishing community-wide standards, fostering collaborative networks, and enhancing brain cell classification efforts. We propose a transcriptional architecture that encodes synaptic communication patterns in the striatum, comprising of cell-adhesion molecules (CAMs), transmitter/modulator receptors, ion channels, signaling proteins, neuropeptides, vesicular release components, and transcription factors. This classification serves as a foundation for finely mapping and integrating publicly available datasets, showcasing the value of deep sampling in defined brain regions for comprehensive brain-wide analyses. Importantly, this nomenclature can serve as a template for other brain regions. Crucially, our proposed molecular phenotypes enable the precise mapping of cellular alterations in Parkinson's Disease. Transcriptional changes predominantly occur in specific cell states of medium spiny neurons within the putamen matrix, leading to increased excitability. Additionally, a disbalance in specific interneuron cell states is associated with heightened glutamatergic signaling, further contributing to increased overall excitability.","abstract":"Precise determination of cellular identity and molecular phenotypes through advanced high-throughput technologies is crucial for understanding intricate tissue functions, especially in complex organs like the brain. This becomes pivotal for a comprehensive mapping of cell identities throughout the human brain to unravel its function. In this study, we present findings from a multi-center investigation involving seven genome centers. We analyzed single-nucleus transcriptomes obtained from NeuN+ neurons from the putamen and caudate nucleus of both healthy individuals and Parkinson's Disease (PD) patients. Our results demonstrate the potential for establishing community-wide standards, fostering collaborative networks, and enhancing brain cell classification efforts. We propose a transcriptional architecture that encodes synaptic communication patterns in the striatum, comprising of cell-adhesion molecules (CAMs), transmitter/modulator receptors, ion channels, signaling proteins, neuropeptides, vesicular release components, and transcription factors. This classification serves as a foundation for finely mapping and integrating publicly available datasets, showcasing the value of deep sampling in defined brain regions for comprehensive brain-wide analyses. Importantly, this nomenclature can serve as a template for other brain regions. Crucially, our proposed molecular phenotypes enable the precise mapping of cellular alterations in Parkinson's Disease. Transcriptional changes predominantly occur in specific cell states of medium spiny neurons within the putamen matrix, leading to increased excitability. Additionally, a disbalance in specific interneuron cell states is associated with heightened glutamatergic signaling, further contributing to increased overall excitability.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007676","title":"Characterization of the molecular signature of human monocytes in aging and myelodysplastic syndrome","description":"Deep immunophenotypic profiling of peripheral blood immune cells from young and older control subjects as well as patients with MDS was initially performed, using mass cytometry to identify monocyte subpopulations. Abundance of monocyte subpopulations separated the samples from patients with MDS from elderly control subjects was identified. Therefore, targeted immunophenotyping of monocytes was also performed with flow cytometry and RNA sequencing from isolated CD14+ peripheral blood longitudinally in 26 subjects, six young healthy individuals, nine older healthy individuals and eleven patients with MDS.","abstract":"Deep immunophenotypic profiling of peripheral blood immune cells from young and older control subjects as well as patients with MDS was initially performed, using mass cytometry to identify monocyte subpopulations. Abundance of monocyte subpopulations separated the samples from patients with MDS from elderly control subjects was identified. Therefore, targeted immunophenotyping of monocytes was also performed with flow cytometry and RNA sequencing from isolated CD14+ peripheral blood longitudinally in 26 subjects, six young healthy individuals, nine older healthy individuals and eleven patients with MDS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007677","title":"Multi-omic analysis of Down Syndrome in thyroid","description":"Background: Down syndrome (DS) is a chromosomal disorder characterized by trisomy of chromosome 21 and is associated with various health problems. Congenital thyroid dysfunction is a common endocrine abnormality in DS, but its exact cause remains unknown. This work aimed at studying the etiology of congenital thyroid dysfunction in DS.\nMethods: Thyroid tissue of fetuses with DS (n=4) and fetuses without a genetic/developmental abnormality (n=5) were analyzed using histopathological evaluation, RNA sequencing (RNA-seq), and DNA methylation (DNAm) profiling.\nResults: Histological examination showed abnormally developed DS thyroid tissue compared to non-DS/healthy tissue. RNA-seq analysis showed numerous differences in gene expression between DS and healthy thyroid tissue, including significant downregulation of thyroid genes FOXE1, IYD and DIO2. Gene set enrichment analysis showed disruption of vital cellular processes and functions in DS fetal thyroid tissue. Analysis of DNAm and expression quantitative trait methylation (eQTM) analysis identified functional and biologically relevant associations, that can be linked to plausible disrupted pathways in DS.\nConclusions: Based on these observations, we conclude that congenital non-autoimmune thyroid dysfunction in DS is probably a DS-specific form of thyroid dysfunction, characterized by abnormal thyroid development, altered expression of genes that regulate thyroid development and hormone production, and altered expression and DNAm of genes pertaining to numerous vital pathways leading to significant metabolic disturbances. The disturbances as investigated by multi-omics analyses (RNA-seq, DNAm and eQTM analyses) are widely spread over the genome, and presumably caused by the direct and downstream effects of overexpressed chromosome 21 genes (dosage effect), and (epi)genomic disturbances.","abstract":"Background: Down syndrome (DS) is a chromosomal disorder characterized by trisomy of chromosome 21 and is associated with various health problems. Congenital thyroid dysfunction is a common endocrine abnormality in DS, but its exact cause remains unknown. This work aimed at studying the etiology of congenital thyroid dysfunction in DS.\nMethods: Thyroid tissue of fetuses with DS (n=4) and fetuses without a genetic/developmental abnormality (n=5) were analyzed using histopathological evaluation, RNA sequencing (RNA-seq), and DNA methylation (DNAm) profiling.\nResults: Histological examination showed abnormally developed DS thyroid tissue compared to non-DS/healthy tissue. RNA-seq analysis showed numerous differences in gene expression between DS and healthy thyroid tissue, including significant downregulation of thyroid genes FOXE1, IYD and DIO2. Gene set enrichment analysis showed disruption of vital cellular processes and functions in DS fetal thyroid tissue. Analysis of DNAm and expression quantitative trait methylation (eQTM) analysis identified functional and biologically relevant associations, that can be linked to plausible disrupted pathways in DS.\nConclusions: Based on these observations, we conclude that congenital non-autoimmune thyroid dysfunction in DS is probably a DS-specific form of thyroid dysfunction, characterized by abnormal thyroid development, altered expression of genes that regulate thyroid development and hormone production, and altered expression and DNAm of genes pertaining to numerous vital pathways leading to significant metabolic disturbances. The disturbances as investigated by multi-omics analyses (RNA-seq, DNAm and eQTM analyses) are widely spread over the genome, and presumably caused by the direct and downstream effects of overexpressed chromosome 21 genes (dosage effect), and (epi)genomic disturbances.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007678","title":"Investigating_the_clonal_dynamics_in_respiratory_tracts_with_cystic_fibrosis","description":"The aim of this project is to better understand the mutational landscape and its interaction with the microbiome in the airways from patients with cystic fibrosis. Whole genome sequencing data will be generated by laser captured microdissection (LCM) with fresh frozen bronchus and lung parenchymal tissues.","abstract":"Cystic fibrosis (CF) is a genetic disease leading to significant dysbiosis, particularly in the lungs. One critical cause of poor outcomes in CF patients is chronic lung infections. As a result, this project will be investigating the clonal dynamics and the interactions between mutational patterns and microbial colonisation in CF respiratory tracts using LCM, aiming to better characterise the pathophysiology and stratification of the disease.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007679","title":"Investigating_the_clonal_dynamics_in_interstitial_lung_diseases_using_laser_captured_microdissection","description":"This study aims to characterise the mutational landscape and identify driver mutations in interstitial lung diseases (ILDs) including idiopathic pulmonary fibrosis, secondary pulmonary fibrosis overlapping with autoimmune conditions as well as stage IV sarcoidosis. Here, we will perform laser-captured microdissection and generate whole genome sequencing data with fresh frozen bronchus and lung parenchymal tissues from patients with ILDs in order to better understand the driving force of these diseases.","abstract":"This study aims to characterise the mutational landscape and identify driver mutations in interstitial lung diseases (ILDs) including idiopathic pulmonary fibrosis, secondary pulmonary fibrosis overlapping with autoimmune conditions as well as stage IV sarcoidosis. Here, we will perform laser-captured microdissection and generate whole genome sequencing data with fresh frozen bronchus and lung parenchymal tissues from patients with ILDs in order to better understand the driving force of these diseases.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-01-04T14:28:17+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007680","title":"Targeting the p53 pathway to treat Malignant Rhabdoid and High-Risk Atypical Teratoid Rhabdoid Tumors","description":"Rhabdoid tumors (RTs) predominantly affect young children and are among the deadliest pediatric solid tumors. Despite multimodal therapy consisting of surgery, radiation, and chemotherapy, children with these tumors have median survival of less than one year. RTs can arise throughout the body, including the central nervous system (CNS) where they are called atypical teratoid rhabdoid tumors (AT/RTs), and in extra-CNS locations such as the kidneys and other soft tissues where they are designated malignant RTs (MRTs). We previously identified MDM2 and MDM4 as therapeutic vulnerabilities in RTs and showed that treatment with the MDM2 inhibitor idasanutlin increased survival in mice bearing MRT xenografts. However, the therapeutic potential of idasanutlin in CNS RT tumors is unknown. Single agent therapies are prone to resistance and show limited clinical benefit on their own. Therefore, we sought to identify combination strategies incorporating idasanutlin that would be effective in both CNS and extra-CNS RTs. Here, we show that the XPO1 inhibitor selinexor increased nuclear retention of p53 and potentiated idasanutlin-induced p53 pathway activation and cytotoxicity in AT/RT and MRT cell lines in vitro. Importantly, combination therapy limited acquired resistance through TP53 mutation.  In vivo, combination therapy was well-tolerated, reduced tumor burden, and increased survival in orthotopic models of both AT/RT and MRT. Our results demonstrate that combining idasanutlin with selinexor is a promising therapeutic strategy for children with rhabdoid tumors.","abstract":"Rhabdoid tumors (RTs) predominantly affect young children and are among the deadliest pediatric solid tumors. Despite multimodal therapy consisting of surgery, radiation, and chemotherapy, children with these tumors have median survival of less than one year. RTs can arise throughout the body, including the central nervous system (CNS) where they are called atypical teratoid rhabdoid tumors (AT/RTs), and in extra-CNS locations such as the kidneys and other soft tissues where they are designated malignant RTs (MRTs). We previously identified MDM2 and MDM4 as therapeutic vulnerabilities in RTs and showed that treatment with the MDM2 inhibitor idasanutlin increased survival in mice bearing MRT xenografts. However, the therapeutic potential of idasanutlin in CNS RT tumors is unknown. Single agent therapies are prone to resistance and show limited clinical benefit on their own. Therefore, we sought to identify combination strategies incorporating idasanutlin that would be effective in both CNS and extra-CNS RTs. Here, we show that the XPO1 inhibitor selinexor increased nuclear retention of p53 and potentiated idasanutlin-induced p53 pathway activation and cytotoxicity in AT/RT and MRT cell lines in vitro. Importantly, combination therapy limited acquired resistance through TP53 mutation.  In vivo, combination therapy was well-tolerated, reduced tumor burden, and increased survival in orthotopic models of both AT/RT and MRT. Our results demonstrate that combining idasanutlin with selinexor is a promising therapeutic strategy for children with rhabdoid tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007681","title":"Mutational_burden_in_skin_following_UV_treatment_Nanoseq","description":"We wish to assess the changes in mutational burden in patients under going UV treatment for psoriasis.  Using duplex sequencing we will assess mutational burden in traditionally sun exposed (arm) and non-sun exposed (buttock) skin epidermis both pre and post UV treatment.","abstract":"We wish to assess the changes in mutational burden in patients under going UV treatment for psoriasis.  Using duplex sequencing we will assess mutational burden in traditionally sun exposed (arm) and non-sun exposed (buttock) skin epidermis both pre and post UV treatment.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-01-05T10:12:02+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007682","title":"Mutational_burden_in_skin_following_UV_treatment_WGS","description":"We wish to assess the changes in mutational burden in patients under going UV treatment for psoriasis.  Using duplex sequencing we will assess mutational burden in traditionally sun exposed (arm) and non-sun exposed (buttock) skin epidermis both pre and post UV treatment.","abstract":"We wish to assess the changes in mutational burden in patients under going UV treatment for psoriasis.  Using duplex sequencing we will assess mutational burden in traditionally sun exposed (arm) and non-sun exposed (buttock) skin epidermis both pre and post UV treatment.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-01-05T10:15:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007683","title":"Leap_Dynamic_Resilience___Adipose_RNA_Managed_Access","description":"Leap Dynamic Resilience - Adipose","abstract":"This project is funded under the Dynamic Resilience programme which aims to address the questions: How do we measure and identify who is at greatest risk of health deterioration after a stress event? Why do some people stay in good health and others not? (In particular, why is it that people who appear equally frail using steady state measures can show very different dynamic responses to stressor events?What causes increased risk of health deterioration after a stress event (independent of individual disease states)? How can we promote dynamic resilience and thus healthy aging for a greater number of people worldwide?","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007684","title":"Leap_Dynamic_Resilience___Tonsil_RNA_Managed_Access","description":"Leap Dynamic Resilience - Tonsil","abstract":"This project is funded under the Dynamic Resilience programme which aims to address the questions: How do we measure and identify who is at greatest risk of health deterioration after a stress event? Why do some people stay in good health and others not? (In particular, why is it that people who appear equally frail using steady state measures can show very different dynamic responses to stressor events?What causes increased risk of health deterioration after a stress event (independent of individual disease states)? How can we promote dynamic resilience and thus healthy aging for a greater number of people worldwide?","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007685","title":"Mosaic_CRISPR_Drug_Combinations___Dual_Guide_EGA","description":"The study aims to perform genome-wide loss-of-function CRISPR-Cas9 screens across genetically annotated human cancer cell lines to identify target combinations. \nAll sequencing is performed on PCR products from the amplification of gRNA segments introduced into the lines.","abstract":"The goal of this project is to identify potential novel drug target combinations for use in cancer biology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007686","title":"Identification of the cause of juvenile parkinsonism in a case_SYNJ1","description":"This study aimed to elucidate the genetic causes underlying the Juvenile\r\nParkinsonism diagnosed in a girl using whole-exome sequencing, analysis\r\nof CAG repeats, RNA sequencing analysis on fibroblasts, and metabolite\r\nidentification. As a result, a homozygous missense mutation SNP T/C\r\n(rs2254562) in SYNJ1 and alteration in metabolism were identified.","abstract":"This study aimed to elucidate the genetic causes underlying the Juvenile\nParkinsonism diagnosed in a girl using whole-exome sequencing, analysis\nof CAG repeats, RNA sequencing analysis on fibroblasts, and metabolite\nidentification. As a result, a homozygous missense mutation SNP T/C\n(rs2254562) in SYNJ1 and alteration in metabolism were identified.","study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-17T12:00:01.319015+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007687","title":"HCA_Thymus_Paediatric_ThyDesign_RNA_Managed_Access","description":"T cells are central to adaptive immunity and thus crucial for understanding and treating human disease. While extensively studied in model organisms, translating this knowledge to humans can sometimes be limited by their rapid cross-species evolution and diverse","abstract":"This study aims to address this gap by studying GRNs directly in the human thymus. To this end, we will apply single nuclei multiomic profiling (10x multiome, scRNA+scATAC) to study thymic cells from the foetal and paediatric human thymus.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-01-17T12:27:45+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007688","title":"Targeted_NanoSeq_for_deep_subclonal_selection_in_ccRCC","description":"Targeted NanoSeq of ccRCC tumours to characterise their deep subclonal landscape and patterns of selection.","abstract":"This study will use Targeted NanoSeq of ccRCC tumours to characterise their deep subclonal landscape and patterns of selection.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007689","title":"Pleuritis_LCM_RE_NanoSeq","description":"Restriction enzyme NanoSeq in pleura of donors with evidence of pleural plaques with and without exposure to asbestos.","abstract":"Investigation of the mutational lanscape of pleura with evidence of pleural plaques.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007690","title":"Pleuritis_LCM_Targeted_NanoSeq","description":"Targeted NanoSeq in pleura of donors with evidence of pleural plaques with and without exposure to asbestos.","abstract":"Investigation of the mutational landscape of pleura with evidence of pleural plaques.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007691","title":"Integration of molecular data for the identification of biomarkers associated with castration resistance in prostate cancer","description":"The present study seeks to assess at the level of expression and metabolic pathways involved, which elements may regulate aggressiveness and resistance to treatment in prostate cancer (PC). Thus, an RNA capture panel has been designed to analyze the expression of the main genes involved in prostate functionality and in the development and progression of cancer in samples of prostate tissue (fresh and FFPE) and plasma; both from PC patients at different stages and control individuals. The analysis of the expression of these genes would allow, thanks to the previous background of the group, to strengthen the application of a prognostic and predictive molecular biomarker, offering a better personalized treatment in this pathology.","abstract":"The present study seeks to assess at the level of expression and metabolic pathways involved, which elements may regulate aggressiveness and resistance to treatment in prostate cancer (PC). Thus, an RNA capture panel has been designed to analyze the expression of the main genes involved in prostate functionality and in the development and progression of cancer in samples of prostate tissue (fresh and FFPE) and plasma; both from PC patients at different stages and control individuals. The analysis of the expression of these genes would allow, thanks to the previous background of the group, to strengthen the application of a prognostic and predictive molecular biomarker, offering a better personalized treatment in this pathology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007692","title":"Single  cell transcriptomics in a pilot study of prostate cancer biopsies","description":"This study is based on single cell transcriptomic analysis of prostate biopsies. A total of 17 patients who used fusion biopsy technology were analysed. Fusion biopsy technology combines MRI and ultrasound images, creating a clearer picture to help locate suspicious areas of prostate cancer. In the study, each patient had tissue taken from the targeted area and from a more distant area. As a result, 34 paired samples were analysed.","abstract":"This study is based on single cell transcriptomic analysis of prostate biopsies. A total of 17 patients who used fusion biopsy technology were analysed. Fusion biopsy technology combines MRI and ultrasound images, creating a clearer picture to help locate suspicious areas of prostate cancer. In the study, each patient had tissue taken from the targeted area and from a more distant area. As a result, 34 paired samples were analysed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007693","title":"Application of genomics in the treatment of prostate cancer, a new step towards precision medicine","description":"This study is based on the sequencing of a panel of genes using next-generation technologies to obtain a large amount of genetic information associated with prostate cancer. This panel includes coding and adjacent non-coding regions of drug metabolising genes as well as those involved in the development and aggressiveness of prostate cancer. To date, 162 samples from patients who respond well to hormone therapy, 106 samples from patients who develop resistance to hormone therapy and 109 control samples have been analysed.","abstract":"This study is based on the sequencing of a panel of genes using next-generation technologies to obtain a large amount of genetic information associated with prostate cancer. This panel includes coding and adjacent non-coding regions of drug metabolising genes as well as those involved in the development and aggressiveness of prostate cancer. To date, 162 samples from patients who respond well to hormone therapy, 106 samples from patients who develop resistance to hormone therapy and 109 control samples have been analysed.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007694","title":"Comprehensive Deep Sequencing Atlas in HCC tumors","description":"Establishment of a comprehensive deep sequencing atlas focused on Hepatocellular Carcinoma (HCC) tumors, employing Whole Genome Sequencing (WGS), RNA Sequencing (RNAseq), and Whole Exome Sequencing (WES). The atlas aims to unravel the intricate genetic landscape of HCC, providing a detailed characterization of genomic alterations, transcriptomic profiles, and key mutations associated with this liver cancer. The integration of WGS, RNAseq, and WES data offers a holistic perspective, facilitating a deeper understanding of the molecular mechanisms driving HCC pathogenesis. The resulting atlas serves as a valuable resource for researchers, clinicians, and the broader scientific community, contributing to advancements in HCC diagnostics, prognostics, and therapeutic interventions.","abstract":"Establishment of a comprehensive deep sequencing atlas focused on Hepatocellular Carcinoma (HCC) tumors, employing Whole Genome Sequencing (WGS), RNA Sequencing (RNAseq), and Whole Exome Sequencing (WES). The atlas aims to unravel the intricate genetic landscape of HCC, providing a detailed characterization of genomic alterations, transcriptomic profiles, and key mutations associated with this liver cancer. The integration of WGS, RNAseq, and WES data offers a holistic perspective, facilitating a deeper understanding of the molecular mechanisms driving HCC pathogenesis. The resulting atlas serves as a valuable resource for researchers, clinicians, and the broader scientific community, contributing to advancements in HCC diagnostics, prognostics, and therapeutic interventions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-01-23T09:52:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007695","title":"Mutational_burden_in_oesophagus__nanoseq_","description":"We wish to accurately assess mutational burden and signature from patients of different ages using clonal oesophageal epithelium and duplex-seq.  We will also attempt to look for differences between smokers and non-smokers and individuals with different levels of alcohol consumption.","abstract":"We wish to accurately assess mutational burden and signature from patients of different ages using clonal oesophageal epithelium and duplex-seq.  We will also attempt to look for differences between smokers and non-smokers and individuals with different levels of alcohol consumption.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-01-23T12:58:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007696","title":"Clonal_human_oesophagus_punches","description":"We wish we perform whole genome sequencing on known clonal libraries of human oesophagus to provide a detailed investigation into differences in mutational burden, copy number and mutational signatures both within and between individuals.","abstract":"We wish we perform whole genome sequencing on known clonal libraries of human oesophagus to provide a detailed investigation into differences in mutational burden, copy number and mutational signatures both within and between individuals.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-01-23T13:04:28+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007697","title":"Single_cell_and_spatial_analysis_of_clonal_architecture_in_spatial_tissue_","description":"The study aims to develop a novel single cell analysis approach that enables simultaneous detection of mutations, transcriptional profiling and spatial mapping of individual cells and to apply the approach to unravel the molecular mechanisms regulating clonal expansion in tissues upon ageing","abstract":"Healthy cells accumulate mutations throughout their life. \nAge-related accumulation of somatic mutations can disrupt cellular function and result in altered tissue homeostasis. Among those, so called driver mutation favour clonal expansion. \nMutation-driven dominant clones have been observed in nearly all tissues, and widely in the hematopoietic system.\nAccumulation of cancer-associated mutations result in clonal expansion and generation of a pre-malignant status.\nIn the hematopoetic system, only stem cell, HSCs, have the capacity for self-renewal and for differentiation into all the different lineages. Clonal expansion driven by accumulation of mutations in the HSCs is refereed as clonal haematopoiesis and is associated with an increased risk of myeloid leukaemia and non-haematological diseases.\nStudying somatic mutations in normal tissues is particularly challenging due to the difficulty of detecting mutations present in single cells or small clones within the tissue. While very recent technological advances are beginning to enable identification of somatic mutation in healthy tissues, the mechanism governing clonal expansion remains elusive. \nUsing cutting edge single cell analysis methods( slide-tag and droplet based single cell RNA-sequencing)  and integrating different sequencing technologies the project aims at producing an innovative dataset to study mutation drive clonal expansion in a variety of tissues in the context of ageing or disease","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007698","title":"Targeted_NanoSeq_frozen_liver_pilot","description":"Targeted NanoSeq in background liver tissue from a number of donors, including donors with and without malignancy, though the samples are only of surrounding background liver tissue, rather than tumour. Each sample has a paired FFPE sample of background liver tissue to compare sequencing output from FFPE v fresh frozen liver tissue.","abstract":"Investigating the driver landscape across chronic liver disease, comparing targeted NanoSeq sequencing output from historical FFPE liver tissue, to paired fresh frozen tissue from the same donor.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007699","title":"Targeted_NanoSeq_FFPE_paired_liver_pilot","description":"Targeted NanoSeq in background liver tissue from a number of donors, including donors with and without malignancy, though the samples are only of surrounding background liver tissue, rather than tumour. Each sample has a paired fresh-frozen sample of background liver tissue to compare sequencing output from FFPE v fresh frozen liver tissue.","abstract":"Investigating the driver landscape across chronic liver disease, comparing targeted NanoSeq sequencing output from historical FFPE liver tissue, to paired fresh frozen tissue from the same donor.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007700","title":"GWAS membranous nephropathy Stanescu et al., 2011 UK cohort, chr2 region of interest, imputed","description":"334 biopsy-confirmed membranous nephropathy (MN) cases and 349 ethnically matched healthy controls: the British cohort of the Stanescu et al., 2011 GWAS. Genotyped and imputed region of interest on chromosome 2 (hg19 chr2:160500000-161500000), as used to determine Neanderthal introgression near the PLA2R1 MN risk locus (lead SNP: rs4664308).","abstract":"334 biopsy-confirmed membranous nephropathy (MN) cases and 349 ethnically matched healthy controls: the British cohort of the Stanescu et al., 2011 GWAS. Genotyped and imputed region of interest on chromosome 2 (hg19 chr2:160500000-161500000), as used to determine Neanderthal introgression near the PLA2R1 MN risk locus (lead SNP: rs4664308).","study_type":"Other","pubmed_ids":[21323541],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007701","title":"DERMATLAS__Porocarcinoma_WES_NovaseqX","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Pigmented spindle cell nevus.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Pigmented spindle cell nevus.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007702","title":"DERMATLAS__Poroma_WES_NovaseqX","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are poromas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are poromas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007703","title":"NOTCH1 fusion genes in pediatric T-cell lymphoblastic lymphoma hallmark a common high-risk subgroup with blood TARC levels as possible biomarker","description":"T-cell lymphoblastic lymphoma (T-LBL) is a common pediatric malignancy accounting for approximately 20% of the non-Hodgkin lymphomas during childhood. Survival rates of T-LBL are ~80%, but outcome after relapse is dismal, with salvage rates reaching only ~15. Considering the extremely poor prognosis after relapse and absence of clinically relevant high-risk genetics, there is an urgent need for the identification of molecular risk factors and new prognostic biomarkers in T-LBL, as well as identification of new therapeutic strategies. In this study we present a novel entity of high-risk pediatric T-LBL patients characterized by previously unknown NOTCH1 gene fusions and highly elevated blood TARC levels","abstract":"T-cell lymphoblastic lymphoma (T-LBL) is a common pediatric malignancy accounting for approximately 20% of the non-Hodgkin lymphomas during childhood. Survival rates of T-LBL are ~80%, but outcome after relapse is dismal, with salvage rates reaching only ~15. Considering the extremely poor prognosis after relapse and absence of clinically relevant high-risk genetics, there is an urgent need for the identification of molecular risk factors and new prognostic biomarkers in T-LBL, as well as identification of new therapeutic strategies. In this study we present a novel entity of high-risk pediatric T-LBL patients characterized by previously unknown NOTCH1 gene fusions and highly elevated blood TARC levels","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-01-31T13:42:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007704","title":"Human NXPE1 mediates variation in sialic acid O-acetylation in Colon Tissue","description":"Sialylation, and its modifications, have important consequences for development, differentiation and immune system regulation in nearly all human tissues. An accounting of all the genes responsible for modifying sialic acids is incomplete, with only one pathway for O-acetylation being well-defined in humans. Using whole genome sequencing of normal human colorectal tissue we identify a haplotype on chromosome 11 that is associated with differences in mild periodic acid Schiff staining (mPAS), a marker of acetylation of sialic acids. Of the genes in this region, only SNPs from NXPE1 correlate perfectly in a validation data set. NXPE1 protein expression by IHC also correlates with mPAS staining patterns in homozygous, as well as heterozygous colon crypts that have undergone spontaneous gain of the mPAS phenotype. Manipulation of NXPE1 expression with CRISPR-Cas9 causes changes to modified sialic acid levels in both 2D cell line and 3D normal colon organoid models. These findings suggest NXPE1 may cause O-acetylation of sialic acids in colorectal tissue, potentially defining NXPE as a new family of sialic acid-modifying genes.","abstract":"Sialylation, and its modifications, have important consequences for development, differentiation and immune system regulation in nearly all human tissues. An accounting of all the genes responsible for modifying sialic acids is incomplete, with only one pathway for O-acetylation being well-defined in humans. Using whole genome sequencing of normal human colorectal tissue we identify a haplotype on chromosome 11 that is associated with differences in mild periodic acid Schiff staining (mPAS), a marker of acetylation of sialic acids. Of the genes in this region, only SNPs from NXPE1 correlate perfectly in a validation data set. NXPE1 protein expression by IHC also correlates with mPAS staining patterns in homozygous, as well as heterozygous colon crypts that have undergone spontaneous gain of the mPAS phenotype. Manipulation of NXPE1 expression with CRISPR-Cas9 causes changes to modified sialic acid levels in both 2D cell line and 3D normal colon organoid models. These findings suggest NXPE1 may cause O-acetylation of sialic acids in colorectal tissue, potentially defining NXPE as a new family of sialic acid-modifying genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-01-31T14:15:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007705","title":"DERMATLAS__Poroma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are poromas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are poromas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-02-01T10:37:11+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007706","title":"Targeted_NanoSeq_liver_needle_biopsy_pilot","description":"Targeted NanoSeq in small volume needle biopsies of background liver tissue. To ascertain minimal length of needle biopsy which can reliably yield enough DNA for targeted NanoSeq.","abstract":"Understanding DNA yields from samples taken from small volume routine diagnostic needle biopsies will allow us to utilise a wealth of liver tissue surplus to diagnostic clinical requirements. These findings will be applied to the wider MASLD cohort.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007707","title":"Targeted_NanoSeq_FFPE_paired_liver_pilot_repaired","description":"Targeted NanoSeq in background liver tissue from a number of donors, including donors with and without malignancy, though the samples are only of surrounding background liver tissue, rather than tumour. Each sample has a paired fresh-frozen sample of background liver tissue to compare sequencing output from FFPE v fresh frozen liver tissue.","abstract":"Investigating the driver landscape across chronic liver disease, comparing targeted NanoSeq sequencing output from historical FFPE liver tissue, to paired fresh frozen tissue from the same donor. \n3 arms to the study - Fresh frozen (Control), FFPE (unrepaired, standard library preparation), FFPE repaired with UDG enzyme removal of uracil artefacts.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007708","title":"Evaluation of EBUS-TBNA Aspirates from Advanced NSCLC for Comprehensive Sequencing Platforms Including Whole Genome Sequencing","description":"Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is often the only source of tumor tissue from patients with advanced, inoperable lung cancer. EBUS-TBNA aspirates are used for the diagnosis, staging, and genomic testing to inform therapy options. Here we extracted DNA and RNA from 220 EBUS-TBNA aspirates to evaluate their suitability for whole genome (WGS), whole exome (WES), and comprehensive panel sequencing. For a subset of 40 cases, the same nucleic acid extraction was sequenced using WGS, WES, and the TruSight Oncology 500 assay. Genomic features were compared between sequencing platforms and compared with those reported by clinical testing. A total of 204 aspirates (92.7%) had sufficient DNA (100 ng) for comprehensive panel sequencing, and 109 aspirates (49.5%) had sufficient material for WGS. Comprehensive sequencing platforms detected all seven clinically reported tier 1 actionable mutations, an additional three (7%) tier 1 mutations, six (15%) tier 2–3 mutations, and biomarkers of potential immunotherapy benefit (tumor mutation burden and microsatellite instability). As expected, WGS was more suited for the detection and discovery of emerging novel biomarkers of treatment response. WGS could be performed in half of all EBUS-TBNA aspirates, which points to the enormous potential of EBUS-TBNA as source material for large, well-curated discovery-based studies for novel and more effective predictors of treatment response. Comprehensive panel sequencing is possible in the vast majority of fresh EBUS-TBNA aspirates and enhances the detection of actionable mutations over current clinical testing.","abstract":"Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is often the only source of tumor tissue from patients with advanced, inoperable lung cancer. EBUS-TBNA aspirates are used for the diagnosis, staging, and genomic testing to inform therapy options. Here we extracted DNA and RNA from 220 EBUS-TBNA aspirates to evaluate their suitability for whole genome (WGS), whole exome (WES), and comprehensive panel sequencing. For a subset of 40 cases, the same nucleic acid extraction was sequenced using WGS, WES, and the TruSight Oncology 500 assay. Genomic features were compared between sequencing platforms and compared with those reported by clinical testing. A total of 204 aspirates (92.7%) had sufficient DNA (100 ng) for comprehensive panel sequencing, and 109 aspirates (49.5%) had sufficient material for WGS. Comprehensive sequencing platforms detected all seven clinically reported tier 1 actionable mutations, an additional three (7%) tier 1 mutations, six (15%) tier 2–3 mutations, and biomarkers of potential immunotherapy benefit (tumor mutation burden and microsatellite instability). As expected, WGS was more suited for the detection and discovery of emerging novel biomarkers of treatment response. WGS could be performed in half of all EBUS-TBNA aspirates, which points to the enormous potential of EBUS-TBNA as source material for large, well-curated discovery-based studies for novel and more effective predictors of treatment response. Comprehensive panel sequencing is possible in the vast majority of fresh EBUS-TBNA aspirates and enhances the detection of actionable mutations over current clinical testing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-02-01T23:03:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007709","title":"A proof-of-concept study of sequential treatment with the HDAC inhibitor vorinostat following BRAF and MEK inhibitors in BRAFV600 mutated melanoma","description":"\"Purpose:\nDevelopment of resistance limits the clinical benefit of BRAF and MEK inhibitors (BRAFi/MEKi) in BRAFV600 mutated melanoma. It has been shown that short-term treatment (14 days) with vorinostat was able to initiate apoptosis of the resistant tumor cells. We aimed to assess the anti-tumor activity of sequential treatment with vorinostat following BRAFi/MEKi in patients with BRAFV600 melanoma who progressed after initial response to BRAFi/MEKi. \n\nPatients and Methods: \nPatients with BRAFi/MEKi resistant BRAFV600 melanoma were treated with vorinostat 360 mg QD for 14 days followed by BRAFi/MEKi. The primary endpoint was an objective response rate of progressive lesions of at least 30% according to RECIST 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, pharmacokinetics of vorinostat and translational molecular analyses using ctDNA and tumor biopsies. \n\nResults:\nTwenty-six patients with progressive BRAFi/MEKi resistant BRAFV600 mutated melanoma received treatment with vorinostat. Twenty-two patients were evaluable for response. The ORR was 9% (one complete response for 31.2 months and one partial response for 14.9 months.  Median PFS and OS were 1.4 and 5.4 months, respectively. Common adverse events were fatigue (23%) and nausea (19%). ctDNA analysis showed emerging secondary mutations in NRAS and MEK in eight patients at time of BRAFi/MEKi resistance. Elimination of these mutations by vorinostat treatment was observed in three patients. \n\nConclusions:\nIntermittent treatment with vorinostat in patients with resistant BRAFV600 mutated melanoma is well tolerated. Although the primary endpoint of this study was not met, durable anti-tumor responses were observed in a minority of patients (9%). \n\"","abstract":"\"Purpose:\nDevelopment of resistance limits the clinical benefit of BRAF and MEK inhibitors (BRAFi/MEKi) in BRAFV600 mutated melanoma. It has been shown that short-term treatment (14 days) with vorinostat was able to initiate apoptosis of the resistant tumor cells. We aimed to assess the anti-tumor activity of sequential treatment with vorinostat following BRAFi/MEKi in patients with BRAFV600 melanoma who progressed after initial response to BRAFi/MEKi. \n\nPatients and Methods: \nPatients with BRAFi/MEKi resistant BRAFV600 melanoma were treated with vorinostat 360 mg QD for 14 days followed by BRAFi/MEKi. The primary endpoint was an objective response rate of progressive lesions of at least 30% according to RECIST 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, pharmacokinetics of vorinostat and translational molecular analyses using ctDNA and tumor biopsies. \n\nResults:\nTwenty-six patients with progressive BRAFi/MEKi resistant BRAFV600 mutated melanoma received treatment with vorinostat. Twenty-two patients were evaluable for response. The ORR was 9% (one complete response for 31.2 months and one partial response for 14.9 months.  Median PFS and OS were 1.4 and 5.4 months, respectively. Common adverse events were fatigue (23%) and nausea (19%). ctDNA analysis showed emerging secondary mutations in NRAS and MEK in eight patients at time of BRAFi/MEKi resistance. Elimination of these mutations by vorinostat treatment was observed in three patients. \n\nConclusions:\nIntermittent treatment with vorinostat in patients with resistant BRAFV600 mutated melanoma is well tolerated. Although the primary endpoint of this study was not met, durable anti-tumor responses were observed in a minority of patients (9%). \n\"","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-04-02T09:10:24.345029+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007710","title":"Nala GSI GSAv3 PGx Study","description":"Background: Microarrays are a well-established and widely adopted technology capable of interrogating hundreds of thousands of loci across the human genome. Combined with imputation to cover common variants not included in the chip design, they offer a cost-effective solution for large-scale genetic studies. Beyond research applications, this technology can be applied for testing pharmacogenomics, nutrigenetics, and complex disease risk prediction. However, establishing clinical reporting workflows requires a thorough evaluation of the assay's performance, which is achieved through validation studies. In this study, we performed pre-clinical validation of a genetic testing workflow based on the Illumina Global Screening Array for 25 pharmacogenomic-related genes. \nMethods: To evaluate the accuracy of our workflow, we conducted multiple pre-clinical validation studies. Here, we present the results of accuracy and precision assessments, involving a total of 73 cell lines. These assessments encompass reference materials from the Genome-In-A-Bottle (GIAB), the Genetic Testing Reference Material Coordination Program (GeT-RM) projects, as well as additional samples from the 1000 Genomes project (1KGP). We conducted an accuracy assessment of genotype calls for target loci in each indication against established truth sets. \nResults: In our per-sample analysis, we observed a mean analytical sensitivity of 99.39% and specificity 99.98%. We further assessed the accuracy of star-allele calls by relying on established diplotypes in the GeT-RM catalogue or calls made based on 1KGP genotyping. On average, we detected a diplotype concordance rate of 96.47% across 14 pharmacogenomic-related genes with star allele-calls. Lastly, we evaluated the reproducibility of our findings across replicates and observed 99.48% diplotype and 100 % phenotype inter-run concordance. \nConclusion: Our comprehensive validation study demonstrates the robustness and reliability of the developed workflow, supporting its readiness for further development for applied testing.","abstract":"Background: Microarrays are a well-established and widely adopted technology capable of interrogating hundreds of thousands of loci across the human genome. Combined with imputation to cover common variants not included in the chip design, they offer a cost-effective solution for large-scale genetic studies. Beyond research applications, this technology can be applied for testing pharmacogenomics, nutrigenetics, and complex disease risk prediction. However, establishing clinical reporting workflows requires a thorough evaluation of the assay's performance, which is achieved through validation studies. In this study, we performed pre-clinical validation of a genetic testing workflow based on the Illumina Global Screening Array for 25 pharmacogenomic-related genes. \nMethods: To evaluate the accuracy of our workflow, we conducted multiple pre-clinical validation studies. Here, we present the results of accuracy and precision assessments, involving a total of 73 cell lines. These assessments encompass reference materials from the Genome-In-A-Bottle (GIAB), the Genetic Testing Reference Material Coordination Program (GeT-RM) projects, as well as additional samples from the 1000 Genomes project (1KGP). We conducted an accuracy assessment of genotype calls for target loci in each indication against established truth sets. \nResults: In our per-sample analysis, we observed a mean analytical sensitivity of 99.39% and specificity 99.98%. We further assessed the accuracy of star-allele calls by relying on established diplotypes in the GeT-RM catalogue or calls made based on 1KGP genotyping. On average, we detected a diplotype concordance rate of 96.47% across 14 pharmacogenomic-related genes with star allele-calls. Lastly, we evaluated the reproducibility of our findings across replicates and observed 99.48% diplotype and 100 % phenotype inter-run concordance. \nConclusion: Our comprehensive validation study demonstrates the robustness and reliability of the developed workflow, supporting its readiness for further development for applied testing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-02-05T11:57:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007711","title":"Karyotype Evolution in Response to Chemoradiotherapy and Upon Recurrence of Esophageal Adenocarcinomas","description":"The genome of esophageal adenocarcinoma (EAC) is highly unstable and might evolve over time. Here, we track karyotype evolution in EACs in response to treatment and upon recurrence through multi-region and longitudinal analysis. To this end, we introduce L-PAC, a bio-informatics technique that allows inference of absolute copy number aberrations (CNA) of low-purity samples by leveraging information of high-purity samples from the same cancer. Quantitative analysis of matched absolute CNAs reveals that the amount of karyotype evolution induced by chemoradiotherapy (CRT) is predictive for early recurrence and depends on the initial level of karyotype intra-tumor heterogeneity. We observe that CNAs acquired in response to CRT are partially reversed back to the initial state upon recurrence. CRT hence alters the fitness landscape to which tumors can adjust by adapting their karyotype. Together, our results indicate that karyotype plasticity contributes to therapy resistance of EACs.","abstract":"The genome of esophageal adenocarcinoma (EAC) is highly unstable and might evolve over time. Here, we track karyotype evolution in EACs in response to treatment and upon recurrence through multi-region and longitudinal analysis. To this end, we introduce L-PAC, a bio-informatics technique that allows inference of absolute copy number aberrations (CNA) of low-purity samples by leveraging information of high-purity samples from the same cancer. Quantitative analysis of matched absolute CNAs reveals that the amount of karyotype evolution induced by chemoradiotherapy (CRT) is predictive for early recurrence and depends on the initial level of karyotype intra-tumor heterogeneity. We observe that CNAs acquired in response to CRT are partially reversed back to the initial state upon recurrence. CRT hence alters the fitness landscape to which tumors can adjust by adapting their karyotype. Together, our results indicate that karyotype plasticity contributes to therapy resistance of EACs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-03-07T11:37:26.936733+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007712","title":"CD8-targeted IL-2 unleashes tumor-specific immunity in human cancer tissue by reviving the dysfunctional T cell pool","description":"Tumor-specific CD8+ T cells are key effectors of antitumor immunity but are often rendered dysfunctional in the tumor microenvironment. Immune checkpoint blockade can restore antitumor T cell function in some patients, however most do not respond to this therapy, often despite T cell infiltration in their tumors. We here explored a CD8-targeted IL-2 fusion molecule (CD8-IL2) to selectively reactivate intratumoral CD8+ T cells in patient-derived tumor fragments. Treatment with CD8-IL2 broadly armed intratumoral CD8+ T cells with enhanced effector capacity, thereby specifically enabling reinvigoration of the dysfunctional T cell pool to elicit potent immune activity. Notably, the revival of dysfunctional T cells to mediate effector activity by CD8-IL2 depended on simultaneous antigen recognition and was quantitatively and qualitatively superior to that achieved by PD-1 blockade. Finally, CD8-IL2 was able to functionally reinvigorate T cells in tumors resistant to anti-PD-1, underscoring its potential as a novel treatment strategy for cancer patients.","abstract":"Tumor-specific CD8+ T cells are key effectors of antitumor immunity but are often rendered dysfunctional in the tumor microenvironment. Immune checkpoint blockade can restore antitumor T cell function in some patients, however most do not respond to this therapy, often despite T cell infiltration in their tumors. We here explored a CD8-targeted IL-2 fusion molecule (CD8-IL2) to selectively reactivate intratumoral CD8+ T cells in patient-derived tumor fragments. Treatment with CD8-IL2 broadly armed intratumoral CD8+ T cells with enhanced effector capacity, thereby specifically enabling reinvigoration of the dysfunctional T cell pool to elicit potent immune activity. Notably, the revival of dysfunctional T cells to mediate effector activity by CD8-IL2 depended on simultaneous antigen recognition and was quantitatively and qualitatively superior to that achieved by PD-1 blockade. Finally, CD8-IL2 was able to functionally reinvigorate T cells in tumors resistant to anti-PD-1, underscoring its potential as a novel treatment strategy for cancer patients.","study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-02T09:09:45.315473+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007713","title":"Stratton__LCMB_FFPE_studies_HNC","description":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. \n\n\nThis pilot study will investigate opportunities for detecting mutational signatures in samples fixed in formalin and embedded in paraffin (FFPE) for variable lengths of time.","abstract":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. \n\nThis pilot study will investigate opportunities for detecting mutational signatures in samples fixed in formalin and embedded in paraffin (FFPE) for variable lengths of time.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007714","title":"HCA_Female_Reproductive_Paediatric_CZI_Spatial","description":"HCA Female Reproductive Paediatric CZI Spatial Managed Access","abstract":"This project proposes to profile cortex from children ovaries from a unique tissue acquisition resource: a biobank of cryopreserved tissue of the ovarian cortex from children undergoing cancer treatment. Samples are collected prior to cancer treatment and cryopreserved for future fertility treatments, and a variety of spatial techniques (such as 10x visium) will be used to profile pre- and postpubertal ovaries.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007715","title":"Comprehensive Analysis Of Off-Target And On-Target Effects Resulting From Liver-Directed Crispr-Cas9–Mediated Gene Targeting With Adeno-Associated Viral Vectors","description":"Comprehensive genome-wide studies are needed to assess the consequences of adeno-associated virus (AAV) vector–mediated CRISPR-Cas–based gene editing. In this study, we evaluated CRISPR-Cas-mediated on-target and off-target effects and examined the genomic integration events of AAV vectors employed to deliver the CRISPR-Cas components to the liver in neonatal mice. The guide RNA (gRNA) was specifically designed to target the coagulation factor IX gene (F9). Whole-genome sequencing (WGS) was conducted to examine the on-target and off-target insertions/deletions (indels). Genome-wide AAV integration events were identified by WGS and Shearing Extension Primer Tag Selection Ligation-Mediated PCR (S-EPTS/LM-PCR). On-target editing events were quantified using the CRISPResso algorithm, revealing efficient CRISPR targeting (36.45 ± 18.29%) in the F9 locus. In contrast, off-target effects were very rare or below the WGS detection limit since only one single putative insertion was detected out of 118 reads (n = 3), based on &gt;100 computationally predicted off-target sites. S-EPTS/LM-PCR analysis demonstrated that AAV integration occurred most frequently in close proximity to the CRISPR-Cas9 targeted locus in the F9 gene when the F9-specific gRNA was used. This was not the case when a scrambled control gRNA was employed. This suggests that AAV genomes are preferentially captured by CRISPR-Cas9–induced double-strand breaks. In contrast, the large majority of AAV integrations were not in proximity to any of 5000 putative computationally predicted off-target sites (median distance of 70 kb). This is consistent with a low risk of off-target effects after in vivo liver-directed CRISPR-Cas9 gene editing likely due to the specific gRNA design and the transient expression of the CRISPCas9 components in the neonatal dividing hepatocytes. These AAV integrations outside the F9 locus likely represent canonical CRISPR-Cas9–independent AAV integrations. In conclusion, S-EPTS/LM-PCR is an attractive platform to assess the on-target and off-target consequences of CRISPR-Cas9–mediated gene editing in vivo.","abstract":"Comprehensive genome-wide studies are needed to assess the consequences of adeno-associated virus (AAV) vector–mediated CRISPR-Cas–based gene editing. In this study, we evaluated CRISPR-Cas-mediated on-target and off-target effects and examined the genomic integration events of AAV vectors employed to deliver the CRISPR-Cas components to the liver in neonatal mice. The guide RNA (gRNA) was specifically designed to target the coagulation factor IX gene (F9). Whole-genome sequencing (WGS) was conducted to examine the on-target and off-target insertions/deletions (indels). Genome-wide AAV integration events were identified by WGS and Shearing Extension Primer Tag Selection Ligation-Mediated PCR (S-EPTS/LM-PCR). On-target editing events were quantified using the CRISPResso algorithm, revealing efficient CRISPR targeting (36.45 ± 18.29%) in the F9 locus. In contrast, off-target effects were very rare or below the WGS detection limit since only one single putative insertion was detected out of 118 reads (n = 3), based on &gt;100 computationally predicted off-target sites. S-EPTS/LM-PCR analysis demonstrated that AAV integration occurred most frequently in close proximity to the CRISPR-Cas9 targeted locus in the F9 gene when the F9-specific gRNA was used. This was not the case when a scrambled control gRNA was employed. This suggests that AAV genomes are preferentially captured by CRISPR-Cas9–induced double-strand breaks. In contrast, the large majority of AAV integrations were not in proximity to any of 5000 putative computationally predicted off-target sites (median distance of 70 kb). This is consistent with a low risk of off-target effects after in vivo liver-directed CRISPR-Cas9 gene editing likely due to the specific gRNA design and the transient expression of the CRISPCas9 components in the neonatal dividing hepatocytes. These AAV integrations outside the F9 locus likely represent canonical CRISPR-Cas9–independent AAV integrations. In conclusion, S-EPTS/LM-PCR is an attractive platform to assess the on-target and off-target consequences of CRISPR-Cas9–mediated gene editing in vivo.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007716","title":"Luminal breast epithelial cells from wildtype and BRCA mutation carriers harbor copy number alterations commonly associated with breast cancer","description":"Cancer-associated mutations have been documented in normal tissues, but the prevalence and nature of somatic copy number alterations and their role in tumor initiation and evolution is not well understood.  Here, using single cell DNA sequencing, we describe the landscape of CNA variants in >48,000 breast epithelial cells from women with normal or high risk of developing breast cancer. Individual cells with one or two of a specific subset of CNAs (e.g. 1q gain and 16q, 22q, 7q, and 10q loss) are detectable in almost all breast tissues and, in those from BRCA1 or BRCA2 mutations carriers, occurs prior to loss of heterozygosity (LOH) of the wildtype alleles. These CNAs, which are among the most common associated with ductal carcinoma in situ (DCIS) and malignant breast tumors, are enriched almost exclusively in luminal cells and are generally absent from basal myoepithelial cells. Allele-specific analysis of the enriched CNAs reveals that each allele was independently altered, demonstrating convergent evolution of these CNAs in an individual breast. Tissues from BRCA1 or BRCA2 mutation carriers contained a small percentage of cells with extreme aneuploidy, featuring loss of TP53, LOH of BRCA1 or BRCA2, and multiple breast cancer-associated CNAs in addition to one or more of the common CNAs in 1q, 10q or 16q. Notably, cells with intermediate levels of CNAs were not detected, arguing against a stepwise gradual accumulation of CNAs. Overall, our findings demonstrate that chromosomal alterations in normal breast epithelium including from high risk women, link early stage CNAs to clonally expanded tumor genomes .","abstract":"Brugge DLP Study ABSTRACT","study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-14T15:14:43.781551+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007717","title":"noninvasive lung cancer subtyping","description":"Accurate diagnosis of lung cancer is important for treatment decision-making. Currently, the gold standard for diagnosing histological subtypes of lung cancer relies on tumor biopsies. Recently, liquid biopsy, particularly cell-free DNA (cfDNA), has shown promising results in cancer detection and classification. In this study, we investigated the potential of cfDNA methylome for the noninvasive classification of lung cancer histological subtypes. Specifically, we focused on the two most prevalent lung cancer subtypes, lung adenocarcinoma and lung squamous cell carcinoma. Using a fragment-based marker discovery approach, we identified robust subtype-specific methylation markers from tumor samples. These markers were successfully validated in independent cohorts and associated with subtype-specific transcription activity. Leveraging these markers, we constructed a subtype classification model using cfDNA methylation profiles, achieving an AUC of 0.808 in the cross-validation and an AUC of 0.747 in the independent validation. Additionally, tumor copy number variations inferred from cfDNA methylome analysis revealed potential implications for treatment selection. In summary, our study demonstrates the potential of cfDNA methylome analysis for noninvasively lung cancer subtyping, offering insights for cancer monitoring and early detection.","abstract":"Accurate diagnosis of lung cancer is important for treatment decision-making. Currently, the gold standard for diagnosing histological subtypes of lung cancer relies on tumor biopsies. Recently, liquid biopsy, particularly cell-free DNA (cfDNA), has shown promising results in cancer detection and classification. In this study, we investigated the potential of cfDNA methylome for the noninvasive classification of lung cancer histological subtypes. Specifically, we focused on the two most prevalent lung cancer subtypes, lung adenocarcinoma and lung squamous cell carcinoma. Using a fragment-based marker discovery approach, we identified robust subtype-specific methylation markers from tumor samples. These markers were successfully validated in independent cohorts and associated with subtype-specific transcription activity. Leveraging these markers, we constructed a subtype classification model using cfDNA methylation profiles, achieving an AUC of 0.808 in the cross-validation and an AUC of 0.747 in the independent validation. Additionally, tumor copy number variations inferred from cfDNA methylome analysis revealed potential implications for treatment selection. In summary, our study demonstrates the potential of cfDNA methylome analysis for noninvasively lung cancer subtyping, offering insights for cancer monitoring and early detection.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-02-15T01:46:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007718","title":"_Targeted_NanoSeq_paired_liver_pilot_FFPE_unrepaired","description":"Targeted NanoSeq in background liver tissue from a number of donors, including donors with and without malignancy, though the samples are only of surrounding background liver tissue, rather than tumour. Each sample has a paired fresh-frozen sample of background liver tissue to compare sequencing output from FFPE v fresh frozen liver tissue.","abstract":"Comparing targeted NanoSeq sequencing output from historical FFPE liver tissue, to paired fresh frozen tissue from the same donor - to assess DNA yield, single strand drop out and error rates compared to fresh frozen control. FFPE tissue will undergo 3 arms - unrepaired (standard FFPE DNA extraction kit), repaired with UNG (Qiagen advanced FFPE kit) or with NEB advanced FFPE repair kit","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007719","title":"Exome_NanoSeq___early_stage_MASLD_and_healthy_liver","description":"Exome NanoSeq in fresh frozen liver tissue from a number of donors, including donors with and without malignancy. To understand the driver landscape in earlier disease stages and help to curate an up to date gene panel for the spectrum of steatotic liver disease.","abstract":"Investigating the driver landscape across a large number of liver specimens spanning the early stages of MASLD. Initial pilot of small number of samples to assess DNA yield and quality from fine bore needle biopsies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007720","title":"Families_Affected_by_Rare_Developmental_Disorders_Germline_Targeted_NanoSeq","description":"This work aims to study clonal dynamics of pathogenic mutations in male germline using targeted NanoSeq in sperm DNA provided by fathers who have had a children with a develpmental disorder caused by a deno mutation using a custom-designed panel of ~250 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"As men age, the risk of pathogenic mutations in sperm increases, elevating the chances of having a child with a developmental disorder or cancer syndrome. With rising parental ages, the incidence of such disorders in children is growing. There is considerable variation in risk between individuals which we've successfully quantified pathogenic sperm mutations from healthy individuals using NanoSeq. This project aims to sequence the sperm of 140 fathers who have already had children with a clinical disorder to assess their risk of recurrence in future pregnancies. This will assess how the clonal landscape of pathogenic mutations in sperm and risk of fathering a child with a clinical disorder varies for this ascertained cohort compared to the general population.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-02-16T11:35:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007721","title":"LFStumourLCMEMSeq","description":"LCM EM-seq from human tumour samples aimed at characterising the methylation landscape within tumours in patients with inherited cancer predisposition.","abstract":"Li-Fraumeni Syndrome (LFS) is caused by germline variants in tp53 leading to susceptibility to a multitude of cancer types including sarcoma, breast cancer, brain tumours, and adrenocortical carcinomas. Lifetime risk of cancer development in LFS is ~80% for men and ~100% for women. The aim of this study is to understand the timings of key driver events and transcriptional profiles in germline tp53 tumourigenesis and to identify novel opportunities for screening and treatment.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007722","title":"Exome_NanoSeq__China_NCI_DEE_buccal_cells_","description":"Exome NanoSeq in buccal cells obtained from the NCI China cohort, This cohort consists of patients with, and without, bladder cancer who have provided buccal swabs. These patients have been exposed to diesel exhaust fumes. We hope to study the driver landscape in this condition, in addition to paired urothelial samples. This is in collaboration with IARC, based in Lyon, France.","abstract":"Investigating the driver landscape in buccal cells from a diverse cohort, with and without bladder cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007723","title":"Exome_NanoSeq__China_NCI_DEE_urothelial_cells_","description":"Exome NanoSeq in urothelial cells obtained from the NCI China cohort, This cohort consists of patients with, and without, bladder cancer who have provided urine cell pellets. These patients have been exposed to diesel exhaust fumes. We hope to study the driver landscape in this condition, in addition to paired buccal samples. This is in collaboration with IARC, based in Lyon, France.","abstract":"Investigating the driver landscape in urothelial cells from a diverse cohort, with and without bladder cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007724","title":"Exome_NanoSeq__China_NCI_PAH_buccal_cells_","description":"Exome NanoSeq in buccal cells obtained from the NCI China cohort, This cohort consists of patients with, and without, lung cancer who have provided buccal swabs. These patients have been exposed to polycyclic aromatic hydrocarbons and the cohort consists of smokers and non-smokers. This is in collaboration with IARC, based in Lyon, France.","abstract":"Investigating the driver landscape in buccal cells from a diverse cohort, with and without lung cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007725","title":"Targeted_NanoSeq__China_NCI_PAH_buccal_cells_","description":"Targeted NanoSeq in buccal cells obtained from the NCI China cohort, This cohort consists of patients with, and without, lung cancer who have provided buccal swabs. These patients have been exposed to polycyclic aromatic hydrocarbons and the cohort consists of smokers and non-smokers. This is in collaboration with IARC, based in Lyon, France.","abstract":"Investigating the driver landscape in buccal cells from a diverse cohort, with and without lung cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007726","title":"Targeted_NanoSeq__China_NCI_DEE_urothelial_cells_","description":"Targeted NanoSeq in urothelial cells obtained from the NCI China cohort, This cohort consists of patients with, and without, bladder cancer who have provided urine cell pellets. These patients have been exposed to diesel exhaust fumes. We hope to study the driver landscape in this condition, in addition to paired buccal samples. This is in collaboration with IARC, based in Lyon, France.","abstract":"Investigating the driver landscape in urothelial cells from a diverse cohort, with and without bladder cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007727","title":"Targeted_NanoSeq__China_NCI_DEE_buccal_cells_","description":"Targeted NanoSeq in buccal cells obtained from the NCI China cohort, This cohort consists of patients with, and without, bladder cancer who have provided buccal swabs. These patients have been exposed to diesel exhaust fumes. We hope to study the driver landscape in this condition, in addition to paired urothelial samples. This is in collaboration with IARC, based in Lyon, France.","abstract":"Investigating the driver landscape in buccal cells from a diverse cohort, with and without bladder cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007728","title":"Targeted_NanoSeq__Taiwan_NCI_buccal_cells_","description":"Targeted NanoSeq in buccal cells obtained from the NCI Taiwan cohort, This cohort consists of patients with, and without, oral cancer, in addition to dysplasia and risk factors for oral cancer. We hope to sequence the driver landscape of these donors in order to understand more about the risk of developing oral cancers. This is in collaboration with IARC, based in Lyon, France.","abstract":"Investigating the driver landscape in buccal cells from a diverse cohort, with and without risk factors for oral cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007729","title":"Exome_NanoSeq__Taiwan_NCI_buccal_cells_","description":"Exome NanoSeq in buccal cells obtained from the NCI Taiwan cohort, This cohort consists of patients with, and without, oral cancer, in addition to dysplasia and risk factors for oral cancer. We hope to sequence the driver landscape of these donors in order to understand more about the risk of developing oral cancers. This is in collaboration with IARC, based in Lyon, France.","abstract":"Investigating the driver landscape in buccal cells from a diverse cohort, with and without risk factors for oral cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007730","title":"Exome_NanoSeq__ESTAMPA_cervical_cells_","description":"Exome NanoSeq in cervical cells obtained from the ESTAMPA cohort, a multicentre study based in Latin America. These samples have been stored and processed  Lyon, France. We hope to explore the driver landscape in healthy cervical cells, both with and without human papillomavirus, as well as in pre-cancerous lesions. \n\n\nhttps://www.thelancet.com/journals/lanam/article/PIIS2667-193X(23)00167-9/fulltext\nhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0272205","abstract":"Investigating the driver landscape in cervical cells from a diverse cohort, with and without risk factors for cervical carcinoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007731","title":"Targeted_NanoSeq__ESTAMPA_cervical_cells_","description":"Targeted NanoSeq in cervical cells obtained from the ESTAMPA cohort, a multicentre study based in Latin America. These samples have been stored and processed  Lyon, France. We hope to explore the driver landscape in healthy cervical cells, both with and without human papillomavirus, as well as in pre-cancerous lesions. \n\n\nhttps://www.thelancet.com/journals/lanam/article/PIIS2667-193X(23)00167-9/fulltext\nhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0272205","abstract":"Investigating the driver landscape in cervical cells from a diverse cohort, with and without risk factors for cervical carcinoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007732","title":"Understanding_the_epigenetic_landscape_of_seminiferous_tubules_throughout_lifespan","description":"We will use LCM to perform whole-genome and enzyme methyl sequencing of individual seminiferous tubules of human individuals, together with matched colonic crypts. Later, computational analysis will include phylogeny reconstruction, driver identification and analysis of the methylation landscape across lifespan.","abstract":"Over the course of an individual's lifetime, human cells accumulate mutations. The rate of mutation has been shown to differ drastically between somatic and germline tissues. Concretely, in spermatogonia, which are the stem cells from which sperm are generated and from which most genetic variation in the human population. The low mutation rates in spermatogonia were attributed to low rates of ubiquitous mutational processes and may be partially attributable to a low rate of cell division in basal spermatogonia. These results highlight similarities and differences in the maintenance of the germline and soma.\n\nWe will use LCM to perform whole-genome and enzyme methyl sequencing of individual seminiferous tubules of human individuals, together with matched colonic crypts. Later, computational analysis will include phylogeny reconstruction, driver identification and analysis of the methylation landscape across lifespan.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007733","title":"Understanding_the_methylation_landscape_of_colonic_crypts_in_IBD","description":"Inflammatory bowel disease (IBD), which is divided into Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic autoinflammatory condition characterized by repeated flares of intestinal inflammation. Three recent studies showed higher mutation rates in IBD affected crypts and that inflammation shapes tissue remodelling leading to positive selection and clonal expansion of crypts harbouring driver mutations. The three studies identified mutations in genes related to IL-17 signaling, cytokine and pattern recognition receptor pathways, rarely affected in colorectal cancer. These studies suggested that clonal expansions are protected from immune-related degradation through pro-apoptosis resistance and that somatic mutagenesis might contribute to the inflammatory process. We aim to expand on this previous work to further validate and define the presented hypotheses by expanding our analysis to Methylation by obtaining DNA and Methylation data from single crypts in IBD patients using laser-capture microdissection (LCM).\n\nWe will collect fresh frozen colonic biopsies and perform LCM whole-genome and enzyme-methyl sequencing. Later, computational analysis will include phylogeny reconstruction, driver identification and differential methylation analysis.","abstract":"We will collect fresh frozen colonic biopsies and perform LCM whole-genome and enzyme-methyl sequencing. Later, computational analysis will include phylogeny reconstruction, driver identification and differential methylation analysis","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007734","title":"Microbiome confounders and quantitative profiling  CRC","description":"Despite significant progress, recognized microbiota confounders and advances in absolute microbiome quantification remain underused in cancer microbiome research. Here, we study the fecal microbiota of 589 patients at different stages of CRC development. Quantitative Microbiome Profiling based on 16S RNA amplicon-sequencing combined with rigorous confounder control, identified microbiota covariates.","abstract":"Despite significant progress, recognized microbiota confounders and advances in absolute microbiome quantification remain underused in cancer microbiome research. Here, we study the fecal microbiota of 589 patients at different stages of CRC development. Quantitative Microbiome Profiling based on 16S RNA amplicon-sequencing combined with rigorous confounder control, identified microbiota covariates.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007735","title":"TB_Disease_Wellcome_LEAP_Delta_Tissue_Spatial","description":"Spatial transcriptomics study of TB diseased tissue.","abstract":"Spatial transcriptomics study of TB diseased tissue.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007736","title":"DERMATLAS__Superficial_acral_fibromyxoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Superficial acral fibromyxomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Superficial acral fibromyxomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007737","title":"DERMATLAS__Superficial_acral_fibromyxoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Superficial acral fibromyxomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Superficial acral fibromyxomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007738","title":"HCA_Immune_Disease_Haniffa_RNA_Managed_Access","description":"Precision targeting of Primary Central Nervous System Lymphoma and its tumour microenvironment","abstract":"This study aims to collect fresh tissue biopsies in patients with primary CNS lymphoma and to use single cell transcriptomics with linked surface antigen profiling (CITEseq), spatial transcriptomics (Visium) and computational analyses to investigate the landscape of PCNSL tumours and the interactions between ECs, macrophages and PCNSL cells. I will explore the wider context of these interactions in a larger cohort of PCNSL and control testicular lymphoma biopsies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007739","title":"HCA_Immune_Disease_Haniffa_Spatial_Managed_Access","description":"Precision targeting of Primary Central Nervous System Lymphoma and its tumour microenvironment","abstract":"This study aims to collect fresh tissue biopsies in patients with primary CNS lymphoma and to use single cell transcriptomics with linked surface antigen profiling (CITEseq), spatial transcriptomics (Visium) and computational analyses to investigate the landscape of PCNSL tumours and the interactions between ECs, macrophages and PCNSL cells. I will explore the wider context of these interactions in a larger cohort of PCNSL and control testicular lymphoma biopsies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007740","title":"RE_NanoSeq___TwinsUK_Buccal","description":"Utilising restriction enzyme NanoSeq, we hope to explore the somatic mutation burden and mutational signatures in buccal cells from TwinsUK donors. Some donors have paired blood samples and data from this will help contextualise that work. All donors have paired Targeted NanoSeq data from buccal swabs.","abstract":"Investigating the somatic mutation landscape of buccal cells, particularly the mutation burden and mutational signatures, in twins.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-02-29T09:56:14+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007741","title":"HCA_Immune_Tumour_Organoid_co_culture_Teichmann_Garnett_OD_RNA","description":"We will examine the transcriptomic and epigenetic responses of the tumour cells to immune cell co-cultures using a cohort of cancer organoids representing a spectrum of solid tumours, including colorectal, pancreatic, esophageal, and ovarian cancer21–24, using single-cell multi- omics.","abstract":"Large-scale genomic analyses and single-cell atlases have shed light on the heterogeneity of the immune composition across tumour types5–9. However, as the studied samples represent a snapshot of the dynamic tumour-immune interface, how tumour cell states respond to challenges by the immune system remains largely unexplored. Thus, it is not known if cancers derived from different tissues, harboring different genetic alterations, or cancer cells in distinct differentiation states within the same tumour respond differently to immune challenge in order to evade elimination.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007742","title":"Isoform-level profiling of m6A modifications in human brain","description":"Oxford Nanopore direct RNA sequencing (DRS) can quantify isoform expression, modifications and polyA tail lengths, enabling simultaneous investigation of the transcriptome and epitranscriptome. We applied DRS to three post-mortem human brain regions: prefrontal cortex, caudate nucleus and cerebellum.","abstract":"Oxford Nanopore direct RNA sequencing (DRS) can quantify isoform expression, modifications and polyA tail lengths, enabling simultaneous investigation of the transcriptome and epitranscriptome. We applied DRS to three post-mortem human brain regions: prefrontal cortex, caudate nucleus and cerebellum.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-03-04T02:05:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007743","title":"ATACseq_in_oesophageal_epithelium","description":"We wish to try and understand differences in chromatin accessibility in both oesophageal epithelium  between people of different ages and skin epidermis between sites of different sun exposure.","abstract":"We wish to try and understand differences in chromatin accessibility in both oesophageal epithelium  between people of different ages and skin epidermis between sites of different sun exposure.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007744","title":"RNA isoform repertoire of neuropsychiatric risk genes in human brain","description":"Neuropsychiatric disorders are highly complex conditions and the risk of developing a disorder has been tied to hundreds of genomic variants that alter the expression and/or products (isoforms) made by risk genes. However, how these genes contribute to disease risk and onset through altered expression and RNA splicing is not well understood. Here we show our current understanding of gene isoforms is far from complete and reveal the precise splicing profiles of neuropsychiatric disorder risk genes. Combining our new bioinformatic pipeline IsoLamp with nanopore long-read amplicon sequencing, we deeply profiled the RNA isoform repertoire of 31 high-confidence neuropsychiatric disorder risk genes in human brain. We show most risk genes are more complex than previously reported, identifying 443 novel isoforms and 28 novel exons, including isoforms which alter protein domains, and genes such as ATG13 and GATAD2A where most expression was from previously undiscovered isoforms. The greatest isoform diversity was present in the schizophrenia risk gene ITIH4. Mass spectrometry of brain protein isolates confirmed translation of a novel exon skipping event in ITIH4, suggesting a new regulatory mechanism for this gene in brain. Our results emphasize the widespread presence of previously undetected RNA and protein isoforms in brain and provide an effective approach to address this knowledge gap. Uncovering the isoform repertoire of neuropsychiatric risk genes will underpin future analyses of the functional impact these isoforms have on neuropsychiatric disorders, enabling the translation of genomic findings into a pathophysiological understanding of disease.","abstract":"Neuropsychiatric disorders are highly complex conditions and the risk of developing a disorder has been tied to hundreds of genomic variants that alter the expression and/or products (isoforms) made by risk genes. However, how these genes contribute to disease risk and onset through altered expression and RNA splicing is not well understood. Here we show our current understanding of gene isoforms is far from complete and reveal the precise splicing profiles of neuropsychiatric disorder risk genes. Combining our new bioinformatic pipeline IsoLamp with nanopore long-read amplicon sequencing, we deeply profiled the RNA isoform repertoire of 31 high-confidence neuropsychiatric disorder risk genes in human brain. We show most risk genes are more complex than previously reported, identifying 443 novel isoforms and 28 novel exons, including isoforms which alter protein domains, and genes such as ATG13 and GATAD2A where most expression was from previously undiscovered isoforms. The greatest isoform diversity was present in the schizophrenia risk gene ITIH4. Mass spectrometry of brain protein isolates confirmed translation of a novel exon skipping event in ITIH4, suggesting a new regulatory mechanism for this gene in brain. Our results emphasize the widespread presence of previously undetected RNA and protein isoforms in brain and provide an effective approach to address this knowledge gap. Uncovering the isoform repertoire of neuropsychiatric risk genes will underpin future analyses of the functional impact these isoforms have on neuropsychiatric disorders, enabling the translation of genomic findings into a pathophysiological understanding of disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-03-05T00:12:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007745","title":"DERMATLAS__SG_basal_cell_adenoma_and_adenocarcinoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are SG basal cell adenomas and adenocarcinomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are SG basal cell adenomas and adenocarcinomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-03-07T11:24:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007746","title":"DERMATLAS__SG_basal_cell_adenoma_and_adenocarcinoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are SG basal cell adenomas and adenocarcinomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are SG basal cell adenomas and adenocarcinomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-03-07T11:26:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007747","title":"Understanding_the_transcriptomic_consequences_of_driver_mutations_in_IBD_clonal_expansions_through_laser_capture_microscopy_whole_exome_sequencing_and_RNA_sequencing","description":"We will collect fresh frozen colonic biopsies to perform exonic and transcriptomic analysis of IBD crypts. We will use LCM to perform whole-exome and RNA-sequencing of single colonic crypts in IBD patients. Moreover, if exome sequencing appears limited to achieve accurate phylogeny building for some crypts, whole-genome sequencing will be also employed. Later, computational analysis will include phylogeny reconstruction, driver identification and differential gene expression analysis. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"In inflammatory bowel disease (IBD) clonal expansions outside the confines of the crypt have been previously reported. Here, we will provide LCM RNA sequencing and DNA sequencing from individual crypts to better understand the role of clonal expansions and the transcriptomic effects of driver mutations in IBD. This dataset will contain RNA-seq and whole-exome sequencing data generated with Illumina Novaseq.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007748","title":"Understanding_the_transcriptomic_consequences_of_driver_mutations_in_IBD_clonal_expansions_through_laser_capture_microscopy_whole_exome_sequencing_and_RNA_sequencing","description":"We will collect fresh frozen colonic biopsies to perform exonic and transcriptomic analysis of IBD crypts. We will use LCM to perform whole-exome and RNA-sequencing of single colonic crypts in IBD patients. Moreover, if exome sequencing appears limited to achieve accurate phylogeny building for some crypts, whole-genome sequencing will be also employed. Later, computational analysis will include phylogeny reconstruction, driver identification and differential gene expression analysis. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"In inflammatory bowel disease (IBD) clonal expansions outside the confines of the crypt have been previously reported. Here, we will provide LCM RNA sequencing and DNA sequencing from individual crypts to better understand the role of clonal expansions and the transcriptomic effects of driver mutations in IBD. This dataset will contain RNA-seq and whole-exome sequencing data generated with Illumina Novaseq.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007749","title":"MPS - triads","description":"MPS - triads","abstract":"MPS - triads","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007750","title":"Whole blood transcriptomics analysis in Antiphospholipid syndrome in patients with Systemic Lupus Erythematosus","description":"We analyzed whole-blood RNA-sequencing data from 299 SLE patients (108 SLE-aPL-positive, including 67 SLE-APS; 191 SLE-aPL-negative) and 72 matched healthy controls (HC).  Pathway enrichment analysis, unsupervised WGCNA analysis and machine learning were applied to distinguish disease endotypes. Deconvolution analysis was performed to characterize the peripheral blood immune cell profile.","abstract":"We analyzed whole-blood RNA-sequencing data from 299 SLE patients (108 SLE-aPL-positive, including 67 SLE-APS; 191 SLE-aPL-negative) and 72 matched healthy controls (HC).  Pathway enrichment analysis, unsupervised WGCNA analysis and machine learning were applied to distinguish disease endotypes. Deconvolution analysis was performed to characterize the peripheral blood immune cell profile.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007751","title":"Childhood_Cancer_Foetal_Behjati_SRF_WGS_Nanoseq_Managed_Access","description":"An exploratory study using WGS NanoSeq on a bait set of common paediatric cancer genes and cancer predisposition genes to assess mutations, mutational signatures, treatment effect, risk of relapse and to study the development of childhood cancer.","abstract":"An exploratory study using WGS NanoSeq on a bait set of common paediatric cancer genes and cancer predisposition genes to assess mutations, mutational signatures, treatment effect, risk of relapse and to study the development of childhood cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007752","title":"Evolution_of_MSI_status_in_cancer","description":"The aims of this study are to investigate the evolution of MSI status in cancer progression.","abstract":"The aims of this study are to investigate the evolution of MSI status in cancer progression.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007753","title":"NEOPREDICT-Lung: Neoadjuvant Immunotherapy for Resectable NSCLC","description":"Links via:\nDOI: https://doi.org/10.1038/s41591-024-02965-0\nPubMed: https://pubmed.ncbi.nlm.nih.gov/38689060/\nJournal: https://www.nature.com/articles/s41591-024-02965-0\n\nAbstract \n\nAntibodies targeting the immune checkpoint molecules PD-1, PD-L1 and CTLA-4 administered alone or in combination with chemotherapy are standard of care in most patients with metastatic non-small cell lung cancers. When given prior to curative surgery, tumor responses and improved event-free survival are achieved. New antibody combinations may be more efficacious and tolerable. In an ongoing, open-label phase II study, 60 biomarker-unselected, treatment-naïve patients with resectable non-small cell lung cancer were randomized to receive two preoperative doses of nivolumab (anti-PD-1) with or without relatlimab (anti-LAG-3) antibody therapy. The primary study endpoint was feasibility of surgery within 43 days, which was met by all patients. Curative resection was achieved in 95% of patients. Secondary endpoints included pathological and radiographic response rates, pathologically complete resection rates, disease-free and overall survival rates, and safety. Major pathological (≤10% viable tumor cells) and objective radiographic responses were achieved in 27% and 10% (nivolumab), and 30% and 27% (nivolumab and relatlimab) of patients, respectively. In 100% (nivolumab) and 90% (nivolumab and relatlimab) of patients tumors and lymph nodes were pathologically completely resected. With 12 months median duration of follow-up, disease-free survival and overall survival rates at 12 months were 89% and 93% (nivolumab), and 93% and 100% (nivolumab and relatlimab). Both treatments were safe with grade ≥ 3 treatment-emergent adverse events reported in 10% and 13% of patients per study arm. Exploratory analyses provided insights into biological processes triggered by preoperative immunotherapy. This study establishes the feasibility and safety of dual targeting of PD-1 and LAG-3 prior to lung cancer surgery.","abstract":"Links via:\nDOI: https://doi.org/10.1038/s41591-024-02965-0\nPubMed: https://pubmed.ncbi.nlm.nih.gov/38689060/\nJournal: https://www.nature.com/articles/s41591-024-02965-0\n\nAbstract \n\nAntibodies targeting the immune checkpoint molecules PD-1, PD-L1 and CTLA-4 administered alone or in combination with chemotherapy are standard of care in most patients with metastatic non-small cell lung cancers. When given prior to curative surgery, tumor responses and improved event-free survival are achieved. New antibody combinations may be more efficacious and tolerable. In an ongoing, open-label phase II study, 60 biomarker-unselected, treatment-naïve patients with resectable non-small cell lung cancer were randomized to receive two preoperative doses of nivolumab (anti-PD-1) with or without relatlimab (anti-LAG-3) antibody therapy. The primary study endpoint was feasibility of surgery within 43 days, which was met by all patients. Curative resection was achieved in 95% of patients. Secondary endpoints included pathological and radiographic response rates, pathologically complete resection rates, disease-free and overall survival rates, and safety. Major pathological (≤10% viable tumor cells) and objective radiographic responses were achieved in 27% and 10% (nivolumab), and 30% and 27% (nivolumab and relatlimab) of patients, respectively. In 100% (nivolumab) and 90% (nivolumab and relatlimab) of patients tumors and lymph nodes were pathologically completely resected. With 12 months median duration of follow-up, disease-free survival and overall survival rates at 12 months were 89% and 93% (nivolumab), and 93% and 100% (nivolumab and relatlimab). Both treatments were safe with grade ≥ 3 treatment-emergent adverse events reported in 10% and 13% of patients per study arm. Exploratory analyses provided insights into biological processes triggered by preoperative immunotherapy. This study establishes the feasibility and safety of dual targeting of PD-1 and LAG-3 prior to lung cancer surgery.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-03-19T14:33:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007754","title":"Understanding_the_methylation_landscape_of_colonic_crypts_in_IBD_through_whole_genome_and_methylation_sequencing","description":"Whole-genome sequencing data of crypts in inflammatory bowel disease patients.","abstract":"Whole-genome sequencing data of crypts in inflammatory bowel disease patients.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007755","title":"Exome_NanoSeq__AdrenocorticalCarcinomaLFS","description":"Exome NanoSeq in adrenocortical carcinomas from a number of Li-Fraumeni syndrome patients.","abstract":"Investigating the driver landscape across a large number of ACC specimens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007756","title":"Targeted_NanoSeq___AdrenocorticalCarcinomaLFS","description":"Targeted NanoSeq in adrenocortical carcinomas from a number of Li-Fraumeni syndrome patients.","abstract":"Investigating the driver landscape in adrenocortical carcinomas of Li-Fraumeni syndrome patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007757","title":"Whole_Genome_Sequencing_OMELib__LCH_","description":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the Newcastle.","abstract":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the Newcastle.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007758","title":"RNA_Seq_OMELib__LCH_","description":"The transcriptional landscape of haematopoietic cells will be characterized by RNA Seq following amplification of RNA/cDNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the Newcastle.","abstract":"The transcriptional landscape of haematopoietic cells will be characterized by RNA Seq following amplification of RNA/cDNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the Newcastle.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007759","title":"Whole_Genome_Sequencing_PTALib__Lymphoma_","description":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from CSCI.","abstract":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from CSCI.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007760","title":"Exome_NanoSeq__Brain_and_Neurons_","description":"Exome NanoSeq in a number of different brain regions and isolated neurons, from a number of donors. Samples are obtained from patients without a neurological medical history, and those with known Alzheimers dementia.","abstract":"Investigating the driver landscape in the brain and nervous system, across a number of donors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007761","title":"MPN_Tissue_WGS_NanoSeq","description":"An exploration of the somatic mutational landscape of a patient with myeloproliferative neoplasm (MPN) and squamous cell carcinoma (SCC). In particular this study aims to identify mutational signatures present in SCC lesion compared to a region of healthy skin, especially searching for the presence of signatures specific to hydroxycarbamide from previous chemotherapy treatment.","abstract":"An exploration of the somatic mutational landscape of a patient with myeloproliferative neoplasm (MPN) and squamous cell carcinoma (SCC). In particular this study aims to identify mutational signatures present in SCC lesion compared to a region of healthy skin, especially searching for the presence of signatures specific to hydroxycarbamide from previous chemotherapy treatment.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-03-22T08:57:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007762","title":"IBD_Whole_Exome_Sequencing","description":"Whole exome sequencing of patients with Inflammatory Bowel Disease. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"In this study we will undertake whole-exome sequencing of UK IBD cases, this data will be combined with that from IBD cases we have already whole-genome sequenced in the past recent years.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007763","title":"Hypothesis Testing for Predictive Variables","description":"Hypothesis Testing for Predictive Variables","abstract":"Hypothesis Testing for Predictive Variables","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007764","title":"PREGO reference panel - 3234 individuals from Western France. Individuals' birthplaces are available in epsg.io/2154 (RGF93 v1 / Lambert-93 -- France) coordinates.","description":null,"abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-03-27T08:45:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007765","title":"IDH- and H3-wildtype high-grade gliomas in teenage and young adults","description":"Whole exome sequencing of high grade gliomas occurring in teenagers and young adults between the ages of 13 and 30. This study combines methylation array profiling, whole exome sequencing and fusion panel sequencing to provide an integrated diagnosis of tumours in this age group.","abstract":"Whole exome sequencing of high grade gliomas occurring in teenagers and young adults between the ages of 13 and 30. This study combines methylation array profiling, whole exome sequencing and fusion panel sequencing to provide an integrated diagnosis of tumours in this age group.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007766","title":"Discovery of immunotherapy targets for pediatric solid and brain tumors by exon-level expression","description":"Immunotherapy with chimeric antigen receptor T cells for pediatric solid and brain tumors is constrained by available targetable antigens. Cancer-specific exons present a promising reservoir of targets; however, these have not been explored and validated systematically in a pan-cancer fashion. To identify cancer specific exon targets, we analyze 1,532 RNA-seq datasets from 16 types of pediatric solid and brain tumors for comparison with normal tissues using a newly developed workflow. We find 2,933 exons in 157 genes encoding proteins of the surfaceome or matrisome with high cancer specificity either at the gene (n=148) or the alternatively spliced isoform (n=9) level. Expression of selected alternatively spliced targets, including the EDB domain of fibronectin 1, and gene targets, such as COL11A1, are validated in pediatric patient derived xenograft tumors. We generate T cells expressing chimeric antigen receptors specific for the EDB domain or COL11A1 and demonstrate that these have antitumor activity. The full target list, explorable via an interactive web portal (https://cseminer.stjude.org/), provides a rich resource for developing immunotherapy of pediatric solid and brain tumors using gene or AS targets with high expression specificity in cancer.","abstract":"Immunotherapy with chimeric antigen receptor T cells for pediatric solid and brain tumors is constrained by available targetable antigens. Cancer-specific exons present a promising reservoir of targets; however, these have not been explored and validated systematically in a pan-cancer fashion. To identify cancer specific exon targets, we analyze 1,532 RNA-seq datasets from 16 types of pediatric solid and brain tumors for comparison with normal tissues using a newly developed workflow. We find 2,933 exons in 157 genes encoding proteins of the surfaceome or matrisome with high cancer specificity either at the gene (n=148) or the alternatively spliced isoform (n=9) level. Expression of selected alternatively spliced targets, including the EDB domain of fibronectin 1, and gene targets, such as COL11A1, are validated in pediatric patient derived xenograft tumors. We generate T cells expressing chimeric antigen receptors specific for the EDB domain or COL11A1 and demonstrate that these have antitumor activity. The full target list, explorable via an interactive web portal (https://cseminer.stjude.org/), provides a rich resource for developing immunotherapy of pediatric solid and brain tumors using gene or AS targets with high expression specificity in cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-03-27T19:04:29+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007767","title":"Genomic and transcriptomic landscape of T-cell lymphoblastic lymphoma compared to T-cell acute lymphoblastic leukemia: similar subtypes and different fusions","description":"Due to the lower incidence of T-LBL and difficulties in obtaining diagnostic T-LBL material, extensive research on T-LBL has been hampered whereas genetic aberrations in T-ALL are thoroughly characterized. Given the similarities and differences between T-LBL and T-ALL, the question has been raised whether T-LBL and T-ALL represent two different diseases or different manifestations of the same disease. This study aims to identify the genomic and transcriptomic landscape of T-LBL and compare the findings to what is found T-ALL. Comparison of the molecular aberrations between T-LBL and T-ALL can provide insights into the overlap and differences in malignant development between the two entities, which could lead to improved risk stratification in T-LBL in order to eventually adapt T-LBL treatment protocols based on molecular-genetic prognostic factors.","abstract":"Due to the lower incidence of T-LBL and difficulties in obtaining diagnostic T-LBL material, extensive research on T-LBL has been hampered whereas genetic aberrations in T-ALL are thoroughly characterized. Given the similarities and differences between T-LBL and T-ALL, the question has been raised whether T-LBL and T-ALL represent two different diseases or different manifestations of the same disease. This study aims to identify the genomic and transcriptomic landscape of T-LBL and compare the findings to what is found T-ALL. Comparison of the molecular aberrations between T-LBL and T-ALL can provide insights into the overlap and differences in malignant development between the two entities, which could lead to improved risk stratification in T-LBL in order to eventually adapt T-LBL treatment protocols based on molecular-genetic prognostic factors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-04-02T12:31:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007768","title":"Clonal_haematopoiesis_in_healthy_volunteers","description":"Targeted sequencing of healthy volunteers for the presence of clonal haematopoiesis mutations.","abstract":"Clonal haematopoiesis increases in prevalence with advancing age. here, we seek to identify CH carriers from a group of 282 healthy volunteers. Carriers of CH will be recalled for additional studies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007769","title":"Whole_Genome_Sequencing_OMELib__Lymph_","description":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the CSCI.","abstract":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the CSCI.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007770","title":"RNA_Seq_OMELib__Lymph_","description":"The transcriptional landscape of haematopoietic cells will be characterized by RNA Seq following amplification of RNA/cDNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the CSCI.","abstract":"The transcriptional landscape of haematopoietic cells will be characterized by RNA Seq following amplification of RNA/cDNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the CSCI.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007771","title":"Differentiation-associated ISG expression of NK cells in chronic viral hepatitis","description":"Little is known about the effects of ISGs on NK cell responses in chronic viral hepatitis. Here, we determined the expression, regulation and function of ISGs in NK cells with respect to phenotype and function, we performed high-throughput single cell RNA sequencing of circulating CD3-CD56+ NK cells from healthy donors (HD) and patients with chronic HBV or HCV infections.","abstract":"Little is known about the effects of ISGs on NK cell responses in chronic viral hepatitis. Here, we determined the expression, regulation and function of ISGs in NK cells with respect to phenotype and function, we performed high-throughput single cell RNA sequencing of circulating CD3-CD56+ NK cells from healthy donors (HD) and patients with chronic HBV or HCV infections.","study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-23T12:16:11.320347+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007772","title":"LCM_WES__Thyroid_","description":"Whole exome sequencing through the low-input DNA pipeline in thyroid samples. Tissue will be processed either from laser capture microdissection or directly from bulk frozen/fixed/paraffin-embedded tissue. Insights will be gained here directly from the sequencing but also from using the data as a matched normal in Exome Nanoseq. Thyroid samples will be obtained from patients with and without thyroid disease.","abstract":"Investigating the driver landscape in thyroid, in both health and disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-04-09T14:19:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007773","title":"Repli-seq data for 'Replication timing alterations are associated with mutation acquisition during tumour evolution in breast and lung cancer'","description":"The essential process of DNA replication timing during each cell cycle is highly regulated ensuring the correct duplication of the genome. The extent and importance of alterations in this process during malignant transformation has not been extensively explored. Here, we evaluate the impact of altered replication timing (ART) on cancer evolution by analysing replication-timing sequencing of cancer and normal cell lines and 952 whole-genome sequenced lung and breast tumours. We find 6%-18% of the cancer genome displays ART. Genomic regions with a change from early to late replication exhibit an increased mutation rate and distinct mutational signatures, while regions changing from late to early contain genes with increased expression and present a preponderance of APOBEC3-mediated mutation clusters and associated driver mutations. We demonstrate that ART is a relatively early event during cancer evolution and that ART may have a stronger correlation with mutation acquisition than alterations in chromatin structure.","abstract":"The essential process of DNA replication timing during each cell cycle is highly regulated ensuring the correct duplication of the genome. The extent and importance of alterations in this process during malignant transformation has not been extensively explored. Here, we evaluate the impact of altered replication timing (ART) on cancer evolution by analysing replication-timing sequencing of cancer and normal cell lines and 952 whole-genome sequenced lung and breast tumours. We find 6%-18% of the cancer genome displays ART. Genomic regions with a change from early to late replication exhibit an increased mutation rate and distinct mutational signatures, while regions changing from late to early contain genes with increased expression and present a preponderance of APOBEC3-mediated mutation clusters and associated driver mutations. We demonstrate that ART is a relatively early event during cancer evolution and that ART may have a stronger correlation with mutation acquisition than alterations in chromatin structure.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-04-09T14:20:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007774","title":"RENanoSeq__Investigating_the_clonal_dynamics_in_interstitial_lung_diseases_using_laser_captured_microdissection","description":"This study aims to characterise the mutational landscape and identify driver mutations in interstitial lung diseases (ILDs) including idiopathic pulmonary fibrosis, seccondary pulmonary fibrosis overlapping with autoimmune conditions as well as stage IV sarcoidosis. Here, we will perform laser-captured microdissection and generate RE-NanoSeq data with fresh frozen bronchus and lung parenchymal tissues from patients with ILDs in order to better understand the mutational processes in these diseases.","abstract":"This study aims to characterise the mutational landscape and identify driver mutations in interstitial lung diseases (ILDs) including idiopathic pulmonary fibrosis, seccondary pulmonary fibrosis overlapping with autoimmune conditions as well as stage IV sarcoidosis. Here, we will perform laser-captured microdissection and generate RE-NanoSeq data with fresh frozen bronchus and lung parenchymal tissues from patients with ILDs in order to better understand the mutational processes in these diseases.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007775","title":"Single_cell_eQTL_mapping_in_IBD_and_defining_the_transcriptomic_predictors_of_responsiveness_to_biologic_therapies_in_IBD","description":"Study Description                                                                                                                                                                        \n10x genomics experiments are conducted to generate single cell transcriptomics data. The 10x scRNAseq experiments are overloaded by multiplexing 1-5 donors into one pool. Overloading increases the chance of doublets being captured in a single gel emulsion bead. Currently, doublets are removed from downstream analyses, wasting the money spent on sequencing them and increasing the cost of sequencing a singlet (e.g. 40K cells = 0.053p/singlet but 47.5 K cells = 0.056p/singlet, internal rates with 50K reads/cell).  When overloading 10X reactions you can multiplex donors per 10X reaction and deconvolute expression data by genotype. To deconvolute, the blended genome exome pipeline is being considered as the method for generating genotyping data and has the advantage to get both whole exome data at high coverage sequencing (~30X) and whole genome sequencing at low coverage(~4X).  Whole blood samples collected as part of the main study will be sent to scientific operations sample management team for DNA extraction and quality control. Then samples will be passed on to the sequencing team for sample preparation, library preparation and sequencing on the Blended genome exome pipeline.                                                                                                                                                                      \nData set Title                                                                                                                                                                                            \nWhole genome and exome sequencing of IBD Patients recruited as part of the IBD-RESPONSE study                          \nDatset Description                                                                                                                                                                             \nWhole genome sequencing (shallow) and whole exome sequencing (deep) of 1250 participants of the IBD-RESPONSE study.  Raw sequencing data as fastq files and genotyping data as VCF files.       \nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"IBD is a severely debilitating disease that affects around 1 in 200 people in the UK. The two common forms of IBD, ulcerative colitis (UC) and Crohn’s disease (CD), are characterised by chronic relapsing inflammation of the gastrointestinal tract. Current therapies are expensive, have major side-effects, and are ineffective in many patients. For example, 40% of patients do not respond to anti-TNFa therapy (“primary non-response”) and of the 60% that respond, 40% lose response within first year of treatment (secondary loss of response), which is primarily thought to be due to development of anti-drug antibodies (ADAs). Up to 50% of CD patients and 15% of UC patients will ultimately require life-changing surgery for medically refractory disease. There is thus a clear need for more effective therapies and biomarkers that are predictive of disease progression and therapeutic response. Unfortunately, the biological basis of IBD and therapy response are incompletely understood. It is believed that patient outcomes are the result of interactions between genotype, gut microbiome and environment (e.g. smoking, diet, pathogens), all of which influence human cellular phenotypes. The longitudinal IBD-Response study has been funded by the MRC to asses these interactions, and their effect on patient outcomes, in a cohort of 1325 IBD patients recruited from 40 hospitals across the UK who are about to start their first biological therapy (mostly anti-TNFs). With the Blended Genome Exome pipeline, we will be able to generate whole exome sequencing at 30X-40X coverage and whole genome sequencing a low coverage sequencing 3-4X . This has recently launched in DNA pipelines at WSI. \nWe generate single-cell RNA sequencing on PBMCs samples ascertained from blood samples of IBD-Response participants at week zero (baseline sample -prior to drug administration) and week 14 (after drug treatment). To being for cost-efficient we are multiplexing these samples in the 10x single cell RNA sequencing assay (scRNASeq) and genotyping data is needed be able to deconvolute expression data from multiplexed samples.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007776","title":"Exome_NanoSeq___Skin_with_or_without_inflammatory_disease","description":"Exome NanoSeq of skin samples from a number of donors, including donors with and without chronic skin inflammatory disease.","abstract":"Exome NanoSeq of skin samples from a number of donors, including donors with and without chronic skin inflammatory disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007777","title":"LCM_Exome___Skin_with_or_without_inflammatory_skin_disease","description":"Investigating the driver landscape across diverse cell types in the skin with or without chronic skin inflammatory diseases.","abstract":"Investigating the driver landscape across diverse cell types in the skin with or without chronic skin inflammatory diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007778","title":"Targeted_NanoSeq___Skin_with_or_without_inflammatory_skin_disease","description":"Investigating the driver landscape across diverse cell types in the skin with or without chronic skin inflammatory diseases.","abstract":"Investigating the driver landscape across diverse cell types in the skin with or without chronic skin inflammatory diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007779","title":"HCA_Embryo_Foetal_Dev_RNA","description":"Detailed single cell atlas of whole human embryos","abstract":"We propose to generate an in-depth single cell and spatial atlas of human embryos during late organogenesis, at 6/7 post conception weeks (PCW). We will deploy genomics technologies to profile single cells from dissociated tissues and within intact tissue sections, and deploy cutting-edge computational methods to reconstruct, in silico, a three-dimensional atlas of the whole human embryo. \n\nDetailed single cell atlas of whole human embryos\nDeliverables: Complete whole embryo atlas datasets by high-throughput genomics profiling (single cell RNA-sequencing (scRNA-seq), single nuclear RNA-sequencing (snRNA-seq), and accessible chromatin sequencing (ATAC-seq)); and spatial transcriptomics (ST, e.g. 10x Genomics Visium), in situ sequencing (ISS) and multiplex smFISH analysis of tissue sections.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007780","title":"WG_NanoSeq__Carrier_RNA_pilot_","description":"Whole genome NanoSeq with sonication and mung bean exonuclease library preparation on samples extracted with and without carrier RNA. The purpose of this study is to assess whether library preparation in this fashion introduces specific errors into the library preparation and sequencing. This will be important as we move towards using LCM and Targeted/Exome NanoSeq more often. The data generated will be of use to the pancreas NormSeq projects.","abstract":"Whole genome NanoSeq with sonication and mung bean exonuclease library preparation on samples extracted with and without carrier RNA. The purpose of this study is to assess whether library preparation in this fashion introduces specific errors into the library preparation and sequencing. This will be important as we move towards using LCM and Targeted/Exome NanoSeq more often. The data generated will be of use to the pancreas NormSeq projects.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007781","title":"Targeted_NanoSeq__FAP_CUH_Tissue_Bank_","description":"Investigating tissue samples from patients with the inherited tumour predisposition syndrome Familial Adenomatous Polyposis (FAP). We intend to explore the clonality, mutation burden, mutational signatures, copy number variation, structural variation, and driver mutations. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across different tissues in patients with FAP.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007782","title":"LCM_WES__FAP_CUH_Tissue_Bank_","description":"Investigating tissue samples from patients with the inherited tumour predisposition syndrome Familial Adenomatous Polyposis (FAP). We intend to explore the clonality, mutation burden, mutational signatures, copy number variation, structural variation, and driver mutations.","abstract":"Investigating the driver landscape across different tissues in patients with FAP.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007783","title":"Genome-wide DNA Methylation Analysis Reveals a Unique Methylation Pattern for Pleural Mesothelioma Compared to Healthy Pleura and Other Lung Diseases","description":null,"abstract":null,"study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-04-17T16:04:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007784","title":"T Cell Receptor sequencing (TCRseq) was applied to investigate TCR repertoires in 173 post-infection COVID-19 patients.","description":"The cohort included 98 mild and 75 severe cases with a median age of 53. We amplified and sequenced the TCR β chain Complementary Determining Region 3 (CDR3b) and performed bioinformatic analyses to assess repertoire diversity, clonality, and V/J allelic usage between age, sex and severity groups. CDR3b amino acid sequence inference was performed by clustering structural motifs and filtering validated reactive CDR3b to COVID-19.","abstract":"The cohort included 98 mild and 75 severe cases with a median age of 53. We amplified and sequenced the TCR β chain Complementary Determining Region 3 (CDR3b) and performed bioinformatic analyses to assess repertoire diversity, clonality, and V/J allelic usage between age, sex and severity groups. CDR3b amino acid sequence inference was performed by clustering structural motifs and filtering validated reactive CDR3b to COVID-19.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007785","title":"MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__Colorectal___NCCJ","description":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","abstract":"The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. \n\nDifferent patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. \nThrough an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007786","title":"Genomic_Advances_in_Sepsis__GAinS__genotyping","description":"This cohort comprises a subset of pateints enrolled in the Genomic Advances in Sepsis (GAinS) study, an established biobank of adult sepsis patients. Patients with sepsis due to community acquired pneumonia or faecal peritonitis were recruited from 35 hospitals across the UK from 2005-2018, with samples for functional genomics and detailed clinical information collected over the first five days of ICU admission. DNA was extracted from buffy coat or whole blood samples using the Qiagen DNA extraction protocol, the automated Maxwell Blood purification kit (Promega), or the QIAamp Blood Midi kit protocol (Qiagen). Genotyping data were generated using the Illumina HumanOmniExpress BeadChip (295 patients), the Infinium CoreExome BeadChip (655 patients), and the Infinium Global Screening Array BeadChip (307 patients). Genotyping QC and imputation into the Haplotype Reference Consortium was perfomed within each batch. The datasets were combined and following post-imputation filtering data were available on 1168 samples. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"This cohort comprises a subset of pateints enrolled in the Genomic Advances in Sepsis (GAinS) study, an established biobank of adult sepsis patients. Patients with sepsis due to community acquired pneumonia or faecal peritonitis were recruited from 35 hospitals across the UK from 2005-2018, with samples for functional genomics and detailed clinical information collected over the first five days of ICU admission. DNA was extracted from buffy coat or whole blood samples using the Qiagen DNA extraction protocol, the automated Maxwell Blood purification kit (Promega), or the QIAamp Blood Midi kit protocol (Qiagen). Genotyping data were generated using the Illumina HumanOmniExpress BeadChip (295 patients), the Infinium CoreExome BeadChip (655 patients), and the Infinium Global Screening Array BeadChip (307 patients). Genotyping QC and imputation into the Haplotype Reference Consortium was perfomed within each batch. The datasets were combined and following post-imputation filtering data were available on 1168 samples. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-04-22T11:18:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007787","title":"SMRT-seq methylation analysis","description":"SMRT-seq methylation analysis","abstract":"SMRT-seq methylation analysis","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007788","title":"Cancer_Whole_Genome_Nanoseq","description":"We propose to build a genetic knowledge bank of Wilms tumour that integrates clinical outcome\ndata with a genetic, epigenetic, and transcriptomic survey of 1,000 Wilms tumours.","abstract":"The purpose of the knowledge bank is to serve as a community resource and to address the following specific\nquestions about Wilms tumour:\n(1) Do genetic, epigenetic, or transcriptional features predict outcome and thus lend themselves to\ntreatment stratification?\n(2) What are the genetic drivers of Wilms tumour, considering the entire histological spectrum of\nWilms tumour including the most common subtypes classified as intermediate risk?","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007789","title":"Exome_sequencing_of_UK_Birth_Cohorts___Millennium_Cohort_Study","description":"We propose to exome sequence birth cohorts with near complete population coverage (thus addressing the ascertainment biases of previous studies), which have detailed longitudinal cognitive and educational data on parents and children, and for which genotyping chip data are readily available.","abstract":"Birth cohort studies involve repeated surveys of large numbers of individuals from birth and throughout their lives. They collect information useful for a wide range of life course research domains, and biological samples which can be used to derive data from an increasing collection of omic technologies. This rich source of longitudinal data, when combined with genomic data, offers the scientific community valuable insights from population genetics to rare disease associations.\n\nAvon Longitudinal Study of Parents and Children (ALSPAC)recruited 14,775 babies of predominantly White ethnicity in the Avon county of south-west England between 1991 and 1992. Born in Bradford (BiB) is similarly focused on a particular local area, the city of Bradford in the north of England, and recruited 13,858 babies between 2007 and 2011, of whom ~41% self-report as white British and ~59% as other ethnicities, predominantly Pakistani. Millennium Cohort Study (MCS) is a national cohort that recruited 18,827 children born between 2000 and 2002, intentionally over-sampling areas with high child poverty, large ethnic minority populations, and smaller UK nations (Wales, Scotland and Northern Ireland)\n\n \n\nAvailable here is a subset of exome-sequenced parents and children from these studies (CRAMS and post-QC VCFs) as detailed in this data note.\n\n \n\nPhenotypic data is also available  by submitting an application to the corresponding cohort:\n\nhttps://cls.ucl.ac.uk/cls-studies/millennium-cohort-study/ [cls.ucl.ac.uk]","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-04-25T11:31:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007790","title":"Families_Affected_by_Rare_Developmental_Disorders_Long_Read","description":"This work aims to study transmission of pathogenic mutations using long read sequencing of DNA provided by families with a child with a developmental disorder caused by a de novo mutation.","abstract":"As men age, the risk of pathogenic mutations in sperm increases, elevating the chances of having a child with a developmental disorder or cancer syndrome. With rising parental ages, the incidence of such disorders in children is growing. This work aims to study transmission of pathogenic mutations using long read sequencing of DNA provided by families with a child with a developmental disorder caused by a de novo mutation.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007791","title":"HCA_Kidney_Adult_CZI_M2M_DNA_Managed_Access","description":"Investigation of tissue immunity of HiP-CT imaged kidneys","abstract":"The goal of biomedical imaging is in understanding intact human organs from the organ to the cellular scale in three dimensions. To achieve this, hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique is performed using the European Synchrotron Radiation Facility (ESRF)’s Extremely Brilliant Source (EBS). HiP-CT perform non-destructive, three-dimensional (3D) scans with hierarchically increasing resolution to provide a structural overview of whole human kidney followed by higher-resolution volume of interest in kidneys with varying degrees of presentation from normal/control kidneys to some degree of fibrosis and chronic kidney disease (CKD). HiP-CT 3D imaging provides macroscopic organ scale to the microscopic organotypic individual specialised cells and functional units such as the glomeruli in intact human kidneys. Subsequently, downstream analyses including spatial transcriptomic, confocal microscopic evaluation and bioinformatics modelling maps and provides organisational and morphological features that are fundamental to understanding system-level behaviours in healthy and disease kidneys such as CKD.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007792","title":"HCA_Kidney_Adult_CZI_M2M_RNA_Managed_Access","description":"Investigation of tissue immunity of HiP-CT imaged kidneys","abstract":"The goal of biomedical imaging is in understanding intact human organs from the organ to the cellular scale in three dimensions. To achieve this, hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique is performed using the European Synchrotron Radiation Facility (ESRF)’s Extremely Brilliant Source (EBS). HiP-CT perform non-destructive, three-dimensional (3D) scans with hierarchically increasing resolution to provide a structural overview of whole human kidney followed by higher-resolution volume of interest in kidneys with varying degrees of presentation from normal/control kidneys to some degree of fibrosis and chronic kidney disease (CKD). HiP-CT 3D imaging provides macroscopic organ scale to the microscopic organotypic individual specialised cells and functional units such as the glomeruli in intact human kidneys. Subsequently, downstream analyses including spatial transcriptomic, confocal microscopic evaluation and bioinformatics modelling maps and provides organisational and morphological features that are fundamental to understanding system-level behaviours in healthy and disease kidneys such as CKD.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007793","title":"HCA_Kidney_Adult_CZI_M2M_Spatial_Managed_Access","description":"Investigation of tissue immunity of HiP-CT imaged kidneys","abstract":"The goal of biomedical imaging is in understanding intact human organs from the organ to the cellular scale in three dimensions. To achieve this, hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique is performed using the European Synchrotron Radiation Facility (ESRF)’s Extremely Brilliant Source (EBS). HiP-CT perform non-destructive, three-dimensional (3D) scans with hierarchically increasing resolution to provide a structural overview of whole human kidney followed by higher-resolution volume of interest in kidneys with varying degrees of presentation from normal/control kidneys to some degree of fibrosis and chronic kidney disease (CKD). HiP-CT 3D imaging provides macroscopic organ scale to the microscopic organotypic individual specialised cells and functional units such as the glomeruli in intact human kidneys. Subsequently, downstream analyses including spatial transcriptomic, confocal microscopic evaluation and bioinformatics modelling maps and provides organisational and morphological features that are fundamental to understanding system-level behaviours in healthy and disease kidneys such as CKD.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007794","title":"Pan_body_Human_Tissue_WGMS","description":"Exploration of the somatic and epimutational landscape of humans. This study comprises of a pan-body investigation of mutational burden, variant allele frequency (VAF), mutational signature presence, and methylation changes across multiple tissue types. The study utilizes laser-capture microdissection to isolate tissue samples followed by WGMS obtain genomic data and enable the construction of phylogenetic trees.","abstract":"Exploration of the somatic and epimutational landscape of humans. This study comprises of a pan-body investigation of mutational burden, variant allele frequency (VAF), mutational signature presence, and methylation changes across multiple tissue types. The study utilizes laser-capture microdissection to isolate tissue samples followed by WGMS obtain genomic data and enable the construction of phylogenetic trees.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007795","title":"Pan_body_Human_Tissue_WGS_LCMB","description":"Exploration of the somatic and epimutational landscape of humans. This study comprises of a pan-body investigation of mutational burden, variant allele frequency (VAF), mutational signature presence, and methylation changes across multiple tissue types. The study utilizes laser-capture microdissection to isolate tissue samples followed by WGMS obtain genomic data and enable the construction of phylogenetic trees.","abstract":"Exploration of the somatic and epimutational landscape of humans. This study comprises of a pan-body investigation of mutational burden, variant allele frequency (VAF), mutational signature presence, and methylation changes across multiple tissue types. The study utilizes laser-capture microdissection to isolate tissue samples followed by WGMS obtain genomic data and enable the construction of phylogenetic trees.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007796","title":"Exome_NanoSeq__PDAC_adjacent_normal_","description":"Investigating the driver landscape of the normal pancreas adjacent to pancreatic ductal adenocarcinoma using an exome-wide panel.","abstract":"Investigating the driver landscape of the normal pancreas adjacent to pancreatic ductal adenocarcinoma using an exome-wide panel.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007797","title":"Targeted_NanoSeq__PDAC_adjacent_normal_","description":"Investigating the driver landscape of normal pancreatic tissue adjacent to pancreatic ductal adenocarcinoma using a custom-designed panel of ~200 genes.","abstract":"Investigating the driver landscape of normal pancreatic tissue adjacent to pancreatic ductal adenocarcinoma using a custom-designed panel of ~200 genes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007798","title":"NovaSeqX_WGS__cord_blood_","description":"The new implementation of NovaSeq X brings new error profiles. The purpose of this study is to identify the error profiles using whole genome sequencing of ultra-low mutation burden samples (cord blood). The result of this will be the development of a mask to filter out common artefactual mutations and sites. This is a high priority in the department given the significant cost savings.","abstract":"The new implementation of NovaSeq X brings new error profiles. The purpose of this study is to identify the error profiles using whole genome sequencing of ultra-low mutation burden samples (cord blood). The result of this will be the development of a mask to filter out common artefactual mutations and sites. This is a high priority in the department given the significant cost savings.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007799","title":"NovaSeqX_WES__cord_blood_","description":"The new implementation of NovaSeq X brings new error profiles. The purpose of this study is to identify the error profiles using whole exome sequencing of ultra-low mutation burden samples (cord blood). The result of this will be the development of a mask to filter out common artefactual mutations and sites. This is a high priority in the department given the significant cost savings.","abstract":"The new implementation of NovaSeq X brings new error profiles. The purpose of this study is to identify the error profiles using whole exome sequencing of ultra-low mutation burden samples (cord blood). The result of this will be the development of a mask to filter out common artefactual mutations and sites. This is a high priority in the department given the significant cost savings.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007800","title":"NK_single_cell_profiling","description":"The experiment will be divided in 2 steps (1/ pilot, 2/ main dataset). NK cells will be isolated from the blood of healthy individuals (1 donor for pilot, 3 for main). The cells will be expanded in vitro and stimulated at day 14 with different stimuli (e.g. co-culture with K562) for 4 hours (+unstimulated control sample). After stimulation, cells will be collected and sorted based on viability, NK purity (CD56) and activation level (CD107a). Samples will be pooled together with cell hashing then stained with CITE-seq TotalSeq cocktail and loaded on a ChromiumX for single-cell transcriptomics. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Natural killer (NK) cells are lymphoid cells playing a key role in the immune response. In the scope of project IMMERSE (OTAR3086), our objective is to isolate NK cells from healthy individuals, perturb hundreds of genes using CRISPR tools, and subsequently assess the impact on transcriptomics at a single-cell upon stimulation. Only a few limited single-cell datasets have been published and little is known on the diversity of this specific immune cell type and the effects of activation on impact gene expression. In this study, we aim to generate a novel single-cell transcriptomics and targeted proteomics dataset from in vitro expanded NK cells in response to various stimuli.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007801","title":"Treg Atlas","description":"Tissue adaptation is required for regulatory T (Treg) cells to function within organs. Whether this program shares similarities between different tissue-localized immune populations is poorly understood. Here, we addressed this by analyzing single-cell chromatin accessibility data, including the transposable element (TE) landscape, of CD45+ immune cells from different tissues. We identified features of organ-specific tissue adaptation across different immune cells. Focusing on tissue-Treg cells, e\nfound that the Treg tissue adaptation program was conserved in other issue-localized immune cells, such as amphiregulin-producing Th17 cells. Accessible TEs can act as regulatory elements but their contribution to issue adaptation is unclear. TE landscape analysis revealed an enrichment of specific transcription factor binding motifs in TE regions within accessible chromatin peaks. TEs, specifically from the LTR family, were located in enhancer regions and associated with tissue adaptation. These findings broaden our understanding of immune tissue-residency, an important step towards organ-specific immune interventions.","abstract":"Tissue adaptation is required for regulatory T (Treg) cells to function within organs. Whether this program shares similarities between different tissue-localized immune populations is poorly understood. Here, we addressed this by analyzing single-cell chromatin accessibility data, including the transposable element (TE) landscape, of CD45+ immune cells from different tissues. We identified features of organ-specific tissue adaptation across different immune cells. Focusing on tissue-Treg cells, e\nfound that the Treg tissue adaptation program was conserved in other issue-localized immune cells, such as amphiregulin-producing Th17 cells. Accessible TEs can act as regulatory elements but their contribution to issue adaptation is unclear. TE landscape analysis revealed an enrichment of specific transcription factor binding motifs in TE regions within accessible chromatin peaks. TEs, specifically from the LTR family, were located in enhancer regions and associated with tissue adaptation. These findings broaden our understanding of immune tissue-residency, an important step towards organ-specific immune interventions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007802","title":"Addenbrookes_Paediatric_Tumour_TB22_01901_WGS_Managed_Access","description":"A PM Case with the presence of a right lung ALK - Pleuro Pulmonary Blastoma.","abstract":"A PM Case with the presence of a right lung ALK - Pleuro Pulmonary Blastoma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007803","title":"To_profile_the_landscape_of_sebaceous_tumours___RNA","description":"Sebaceous tumours are a rare cutaneous cancer with potential for aggressive behaviour. However, limited information is available on these cancers with few published cases. Here we wish to exome sequence these cancers to define the first genomic landscape for this malignancy. We will extract RNA from formalin-fixed, paraffin-embedded (FFPE) cores. Cores may be obtained from lesional and non-lesional tissues of primaries as well as matching metastases. The extracted RNA will be used for RNA sequencing.","abstract":"Sebaceous tumours are a rare cutaneous cancer with potential for aggressive behaviour. However, limited information is available on these cancers with few published cases. Here we wish to exome sequence these cancers to define the first genomic landscape for this malignancy. We will extract RNA from formalin-fixed, paraffin-embedded (FFPE) cores. Cores may be obtained from lesional and non-lesional tissues of primaries as well as matching metastases. The extracted RNA will be used for RNA sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-05-13T10:34:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007804","title":"DERMATLAS__Cribriform_carcinoma_skin_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Cribriform carcinoma of the skin.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Cribriform carcinoma of the skin.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007805","title":"DERMATLAS__Cribriform_carcinoma_skin_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Cribriform carcinoma of the skin.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Cribriform carcinoma of the skin.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007806","title":"DERMATLAS__Endocrine_mucin_producing_sweat_gland_carcinoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Endocrine mucin-producing sweat gland carcinoma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Endocrine mucin-producing sweat gland carcinoma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007807","title":"DERMATLAS__Endocrine_mucin_producing_sweat_gland_carcinoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Endocrine mucin-producing sweat gland carcinoma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Endocrine mucin-producing sweat gland carcinoma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007808","title":"DERMATLAS__Mucinous_carcinoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Mucinous carcinomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Mucinous carcinomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007809","title":"DERMATLAS__Mucinous_carcinoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Mucinous carcinomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Mucinous carcinomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007810","title":"WGS____CDH1_HDGC","description":"Whole-genome sequencing data of gastric organoids and biopsies from healthy and HDGC patients.","abstract":"Whole-genome sequencing data of gastric organoids and biopsies from healthy and HDGC patients.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007811","title":"RNAseq___CDH1_HDGC","description":"RNAseq of gastric organoids and biopsies from healthy and HDGC patients.","abstract":"Investigating the transcriptome of gastric organoids and biopsies from healthy and HDGC patients.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007812","title":"EMSeq_CDH1_HDGC","description":"Enzyme-methyl sequencing data of gastric organoids and biopsies from healthy and HDGC patients.","abstract":"Investigating the epigenome of gastric organoids and biopsies from healthy and HDGC patients.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007813","title":"Exome_NanoSeq___CDH1_HDGC","description":"Exome NanoSeq of gastric organoids and biopsies from healthy and HDGC patients.","abstract":"Investigating the driver landscape of gastric organoids and biopsies from healthy and HDGC patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007814","title":"Cancer_Cell_Model_RNA_Sequencing_","description":"RNA-Seq of cancer cell models.","abstract":"RNA-Seq of cancer cell models.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007815","title":"Methylome of medulloblastoma data (MB_COMICS cohort)","description":null,"abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-05-15T11:12:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007816","title":"Genetic Effects on the Skin Methylome in Healthy Older Twins","description":null,"abstract":"Whole skin DNA methylation variation has been implicated in several diseases, including melanoma, but its genetic basis has not yet been characterised. Using bulk skin tissue samples from 414 healthy female UK twins, we performed twin-based heritability and methylation Quantitative Trait Loci (meQTL) analyses for &gt;400,000 DNA methylation sites. We find that the human skin DNA methylome is on average less heritable than previously estimated in blood and other tissues (mean heritability: 10.02%). MeQTL analysis identified local genetic effects influencing DNA methylation at 18.8% (76,442) of tested CpG sites, as well as 1,775 CpG sites associated with at least one distal genetic variant. As a functional follow-up we performed skin expression QTL (eQTL) analyses in a partially overlapping sample of 604 female twins. Colocalisation analysis identified over 3,500 shared genetic effects affecting thousands of CpG sites (10,067) and genes (4,475). Mediation analysis of putative colocalised gene-CpG pairs identified 114 genes with evidence for eQTL effects being mediated by DNA methylation in skin, including in genes implicated skin disease such as ALOX12 and CSPG4. We further explored the relevance of skin meQTLs to skin disease, and found that skin meQTLs and CpGs under genetic influence were enriched for multiple skin-related genome-wide and epigenome-wide association signals, including for melanoma and psoriasis. Our findings give insights into the regulatory landscape of epigenomic variation in skin.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-05-15T13:19:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007817","title":"This study aims to evaluate the relationship between cardiometabolic risk factors and the most common genetic variation (SNPs)","description":"Comprehensive data on lifestyle-related modifiable factors, sociodemographic, anthropometric, economic, biochemical, and genetic markers related to the occurrence of cardiometabolic diseases as part of the observational cross-sectional survey “2015 Health Survey of São Paulo with Focus on Nutrition (2015 ISA-Nutrition)”, a population-based study. Data of 805218 SNPs for 841 individuals was genotyped using the Axiom™ 2.0 Precision Medicine Research Array in the Thermo Fisher Scientific laboratory (Affymetrix Inc, Santa Clara, CA).","abstract":"Comprehensive data on lifestyle-related modifiable factors, sociodemographic, anthropometric, economic, biochemical, and genetic markers related to the occurrence of cardiometabolic diseases as part of the observational cross-sectional survey “2015 Health Survey of São Paulo with Focus on Nutrition (2015 ISA-Nutrition)”, a population-based study. Data of 805218 SNPs for 841 individuals was genotyped using the Axiom™ 2.0 Precision Medicine Research Array in the Thermo Fisher Scientific laboratory (Affymetrix Inc, Santa Clara, CA).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007818","title":"This study aims to evaluate the relationship between cardiometabolic risk factors and the most common genetic variation (SNPs)","description":"Comprehensive data on lifestyle-related modifiable factors, sociodemographic, anthropometric, economic, biochemical, and genetic markers related to the occurrence of cardiometabolic diseases as part of the observational cross-sectional survey “2015 Health Survey of Sao Paulo with Focus on Nutrition (2015 ISA-Nutrition)”, a population-based study. Data of 805218 SNPs for 841 individuals was genotyped using the Axiom™ 2.0 Precision Medicine Research Array in the Thermo Fisher Scientific laboratory (Affymetrix Inc, Santa Clara, CA).","abstract":"Comprehensive data on lifestyle-related modifiable factors, sociodemographic, anthropometric, economic, biochemical, and genetic markers related to the occurrence of cardiometabolic diseases as part of the observational cross-sectional survey “2015 Health Survey of Sao Paulo with Focus on Nutrition (2015 ISA-Nutrition)”, a population-based study. Data of 805218 SNPs for 841 individuals was genotyped using the Axiom™ 2.0 Precision Medicine Research Array in the Thermo Fisher Scientific laboratory (Affymetrix Inc, Santa Clara, CA).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-05-16T12:44:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007819","title":"Benchmarking for alignment and variant calling","description":"Background: Lung cancer is a heterogeneous disease and the primary cause of cancer-related mortality worldwide. Somatic mutations, including large structural variants, are important biomarkers in lung cancer for selecting targeted therapy. Genomic studies in lung cancer have been conducted using short-read sequencing. Emerging long-read sequencing technologies are a promising alternative to study somatic structural variants, however there is no current consensus on how to process data and call somatic events. In this study, we preformed whole genome sequencing of lung cancer and matched non-tumour samples using long and short read sequencing to comprehensively benchmark three sequence aligners and six structural variant callers comprised of four generic callers (Sniffles2, cuteSV, SVIM and DELLY in generic mode) and two somatic callers (nanomonsv and DELLY in somatic modes). \nResults: Different combinations of aligners and variant callers influenced somatic structural variant detection. The choice of caller had a significant influence on somatic structural variant detection in terms of variant type, size, sensitivity, and accuracy. The performance of each variant caller was assessed by comparing to somatic structural variants identified by short read sequencing. When compared to somatic structural variants detected with short read sequencing, more events were detected with long read sequencing. The mean recall of somatic variant events identified by short read sequencing was higher for the somatic callers (64%) than generic callers (52%), with nanomonsv (69%) showing the best performance.\nConclusion: Long read sequencing can identify somatic structural variants. The longer reads have the potential to improve our understanding of cancer development and inform personalized cancer treatment.","abstract":"Background: Lung cancer is a heterogeneous disease and the primary cause of cancer-related mortality worldwide. Somatic mutations, including large structural variants, are important biomarkers in lung cancer for selecting targeted therapy. Genomic studies in lung cancer have been conducted using short-read sequencing. Emerging long-read sequencing technologies are a promising alternative to study somatic structural variants, however there is no current consensus on how to process data and call somatic events. In this study, we preformed whole genome sequencing of lung cancer and matched non-tumour samples using long and short read sequencing to comprehensively benchmark three sequence aligners and six structural variant callers comprised of four generic callers (Sniffles2, cuteSV, SVIM and DELLY in generic mode) and two somatic callers (nanomonsv and DELLY in somatic modes). \nResults: Different combinations of aligners and variant callers influenced somatic structural variant detection. The choice of caller had a significant influence on somatic structural variant detection in terms of variant type, size, sensitivity, and accuracy. The performance of each variant caller was assessed by comparing to somatic structural variants identified by short read sequencing. When compared to somatic structural variants detected with short read sequencing, more events were detected with long read sequencing. The mean recall of somatic variant events identified by short read sequencing was higher for the somatic callers (64%) than generic callers (52%), with nanomonsv (69%) showing the best performance.\nConclusion: Long read sequencing can identify somatic structural variants. The longer reads have the potential to improve our understanding of cancer development and inform personalized cancer treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-05-17T01:38:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007820","title":"Targeted_NanoSeq__Coeliac_","description":"Targeted NanoSeq in coeliac disease, focusing on the immune cells infiltrating tissue, in addition to other relevant histologies. The primary tissue is anticipated to be small intestine, such as duodenal biopsies, but this might also extend to other tissues such as the GI tract and the skin. This will be undertaken with a custom panel targeting epithelial and lymphocyte drivers.","abstract":"Investigating the driver landscape in coeliac disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007821","title":"HCA_Immune_NK_Teichmann_Garnett_OD_RNA","description":"The study focuses on less studied cell populations, including adaptive NK cells and innate-like T cells, in order to discover new avenues for cellular immunotherapies.","abstract":"We first aim to map the transcriptional and epigenomic states of adaptive natural killer and innate T cells under different circumstances modeling various microenvironmental challenges to understand the potential phenotypic perturbations imposed on the cells during the course of cell therapy. This will allow us to identify desirable highly functional states as well as undesirable dysfunctional states induced by the microenvironmental perturbations. Such perturbations include interaction with the cancer cells but also interactions with other cells of the microenvironment, as well as various cytokine milieus.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007822","title":"Fenland_Exomes","description":"Wellcome Sanger Institute proposes to exome sequence approximately 34,500 individuals from the ALSPAC, Born in Bradford (BiB) and Fenland cohorts. This proposal will supplement WSI core-funding from the Wellcome Trust to enable comprehensive sequencing of the ALSPAC and BiB cohorts.\n1) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Exome sequencing of the Fenland cohort will empower genetic analysis of a large cohort focused on metabolic diseases with rich longitudinal lifestyle and health information enabling analyses of genetic and environmental contributions to disease. The addition of exome sequencing to these longitudinal cohorts will allow the rigourous assessment of the contribution of rare genetic coding variation to the phenotypic measures collected in these cohorts. Published and unpublished studies of rare protein coding variation in other cohorts (e.g., UKBiobank) have shown the power of this approach and the relevance of this form of genetic variation across broad classes of phenotypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007823","title":"Leap_Dynamic_Resilience___Liver_RNA_Managed_Access","description":"Leap Dynamic Resilience - Liver","abstract":"This project is funded under the Dynamic Resilience programme which aims to address the questions: How do we measure and identify who is at greatest risk of health deterioration after a stress event? Why do some people stay in good health and others not? (In particular, why is it that people who appear equally frail using steady state measures can show very different dynamic responses to stressor events?What causes increased risk of health deterioration after a stress event (independent of individual disease states)? How can we promote dynamic resilience and thus healthy aging for a greater number of people worldwide?","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007824","title":"Blended_genome_exome_sequencing_of_the_Drakenstein_Child_Health_Study","description":"This project continues in a similar vein to the exome sequencing we (the Martin and Hurles groups) have conducted in three British birth cohorts (ALSPAC, Millennium Cohort Study and Born in Bradford). In brief, the goal is to study longitudinal effects of genetic variation on cognitive and behavioural traits in childhood and adolescence, with a view to understanding causes of incomplete penetrance in neurodevelopmental disorders. The British birth cohorts comprise individuals of predominantly European ancestry. We have some very interesting results from these showing that the effect of rare variants on cognition decrease across childhood whereas common variant effects increase. We would like to extend this to other ancestry groups from different environmental settings, to see whether these results hold. However, there is a dearth of appropriate samples with DNA and cognitive/behavioural traits collected longitudinally throughout childhood. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"The Drakenstein Child Health Study, based in Western Cape, South Africa. It comprises ~1,110 mother-child duos recruited while the mother was pregnant between 2012-2015. The cohort was collected from a  isiXhosa-speaking black African community and from an Afrikaans-speaking mixed race community (known as ‘coloured’ in South Africa). These communities are characterised by low rates of educational attainment, high rates of HIV exposure, high prevalence of maternal psychological distress and high rates of drug and alcohol usage (including during pregnancy). Thus, there are substantial differences from the British birth cohorts we have examined so far, in addition to the ancestry differences.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007825","title":"DNAme_heritability_in_solid_tissues__LCM_DNA___NovaSeqX__","description":"Exploring methylation patterns in tissues such as endometrium, colon, stomach, and duodenum. SequenceScape study ID 6891. Updated humfres to reflect new AMSBIO humfre. This study is sequenced using the NovaSeqX platform.","abstract":"Exploring methylation patterns in tissues such as endometrium, colon, stomach, and duodenum.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007826","title":"DNAme_heritability_in_solid_tissues__NovaSeqX__","description":"Pilot study exploring methylation patterns in tissues such as endometrium, colon, stomach, and duodenum. SequenceScape study ID 6855. Updated humfres to reflect new AMSBIO humfre. This study is sequenced on the NovaSeqX platform.","abstract":"Pilot study exploring methylation patterns in tissues such as endometrium, colon, stomach, and duodenum.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007827","title":"LCMB_WGS_masld_NovaSeqX","description":"LCM-B whole-genome sequencing of steatotic livers with histological correlate from laser capture microdissections.","abstract":"Investigating the driver landscape across chronic liver disease, comparing histological correlate to clonal architecture.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007828","title":"Targeted_NanoSeq_FFPE_paired_liver_pilot","description":"Targeted NanoSeq in background liver tissue from a number of donors, including donors with and without malignancy, though the samples are only of surrounding background liver tissue, rather than tumour. Each sample has a paired fresh-frozen sample of background liver tissue to compare sequencing output from FFPE v fresh frozen liver tissue.","abstract":"Investigating the driver landscape across chronic liver disease, comparing targeted NanoSeq sequencing output from historical FFPE liver tissue, to paired fresh frozen tissue from the same donor.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007829","title":"Genomic characterization of a patient with AGS and CdLS transcriptomic comparison of his monocytes against healthy and disease control samples","description":"In this study, we describe an extreme genetic phenotype of two simultaneous genetic lesions, leading to broad alterations in immunophenotype and transcriptome. Whole Exome Sequencing and RNA-Sequencing of CD14+ monocytes was performed on the case patient, and RNA-sequencing was also performed on disease (Systemic Lupus Erythematosus) and healthy controls.","abstract":"In this study, we describe an extreme genetic phenotype of two simultaneous genetic lesions, leading to broad alterations in immunophenotype and transcriptome. Whole Exome Sequencing and RNA-Sequencing of CD14+ monocytes was performed on the case patient, and RNA-sequencing was also performed on disease (Systemic Lupus Erythematosus) and healthy controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007830","title":"CordBlood_EMseq","description":"Cord blood samples will be used to generate a normal panel for use in NovaseqX platform","abstract":"Cord blood samples will be used to generate a normal panel for use in NovaseqX platform","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007831","title":"Measuring the Efficiency of Purging by Nonrandom Mating in Human Populations","description":null,"abstract":"Human populations harbor a high concentration of deleterious genetic variants. Here, we tested the hypothesis that non-random mating practices affect the distribution of these variants, through exposure in the homozygous state, leading to their purging from the population gene pool.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-05-29T12:54:44+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007832","title":"Whole Genome Sequence and RNASeq Samples for Lung Cancer","description":"Short Read Whole Genome Sequence and RNASeq Samples for Lung Cancer","abstract":"Short Read Whole Genome Sequence and RNASeq Samples for Lung Cancer","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-05-30T05:33:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007833","title":"PTA__thyroid_","description":"Investigation into thyroid pathologies utilising single cell/nuclei genome sequencing.","abstract":"Investigation into thyroid pathologies utilising single cell/nuclei genome sequencing.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-05-30T13:17:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007834","title":"PTA_clonal_hematopiesis_","description":"Investigating clonal architecture in clonal haematopoiesis","abstract":"Investigation clonal dynamics in aged medullary and extramedullary haematopoiesis utilising single cell/nuclei genome sequencing.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007835","title":"Targeted_NanoSeq_from_non_invasive_oesophageal_samples","description":"Targeted NanoSeq of non-invasive oesophageal samples from individuals with normal, pre-malignant disease and oesophageal cancer. Both the buccal and a custom-designed targeted sequencing panel of ~300 genes will be used to achieve high depth coverage (aiming for ~500 - 1000dx at panel sites). The driver landscape across different disease phenotypes will be compared to evaluate strategies for risk prediction of oesophageal cancer development.","abstract":"Investigating the driver landscape across individuals at low, intermediate and high-risk for developing oesophageal cancer utilizing non-invasive oesophageal samples with the aim to create prognostic value for cancer risk prediction.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007836","title":"IBD_RESPONSE","description":"IBD is a severely debilitating disease that affects around 1 in 200 people in the UK. The two common forms of IBD, ulcerative colitis (UC) and Crohn’s disease (CD), are characterised by chronic relapsing inflammation of the gastrointestinal tract. Current therapies are expensive, have major side-effects, and are ineffective in many patients. For example, 40% of patients do not respond to anti-TNFa therapy (“primary non-response”) and of the 60% that respond, 40% lose response (secondary loss of response), which is primarily thought to be due to development of anti-drug antibodies (ADAs). Up to 50% of CD patients and 15% of UC patients will ultimately require life-changing surgery for medically refractory disease. There is thus a clear need for more effective therapies and biomarkers that are predictive of disease progression and therapeutic response. Unfortunately, the biological basis of IBD and therapy response are incompletely understood. It is believed that patient outcomes are the result of interactions between genotype, the gut microbiome and the environment (e.g. smoking, diet, pathogens), all of which influence human cellular phenotypes.  Data from the study will answer the following questions: 1. What are the genes, cell-types and pathways that mediate risk of IBD? 2. What are the genes, cell-types and pathways that mediate disease progression and treatment response in IBD? 3. To what extent do single-cell transcriptomes in relevant cells predict disease course and treatment response? 4. What is the causal relationship between the gut microbiome, intestinal gene expression, TCR/BCR variation and IBD progression and drug response.","abstract":"Single cell sequencing of blood and gut biopsies ascertained from IBD patients before and after administration of first biologic therapy (mainly anti-TNFs).\nIBD is a severely debilitating disease that affects around 1 in 200 people in the UK. The two common forms of IBD, ulcerative colitis (UC) and Crohn’s disease (CD), are characterised by chronic relapsing inflammation of the gastrointestinal tract. Current therapies are expensive, have major side-effects, and are ineffective in many patients. For example, 40% of patients do not respond to anti-TNFa therapy (“primary non-response”) and of the 60% that respond, 40% lose response (secondary loss of response), which is primarily thought to be due to development of anti-drug antibodies (ADAs). Up to 50% of CD patients and 15% of UC patients will ultimately require life-changing surgery for medically refractory disease. There is thus a clear need for more effective therapies and biomarkers that are predictive of disease progression and therapeutic response. Unfortunately, the biological basis of IBD and therapy response are incompletely understood. It is thought that patient outcomes are the result of interactions between genotype, the gut microbiome and the environment (e.g. smoking, diet, pathogens), all of which influence host cell phenotypes. The longitudinal IBD-Response study has been funded by the MRC to assess these interactions, and their effect on patient outcomes, in a cohort of 1325 IBD patients recruited from up to 40 hospitals across the UK who are about to start their first biological therapy (mostly anti-TNFs). \nHere, we will generate 10X 5’ scRNA-seq data (including V(D)J sequencing) on gut biopsies samples ascertained from up to 650 IBD-Response participants undergoing routine colonoscopies during the course of the study. Sequencing of 2000-3000 cells per donor will be performed on Illumina Novaseq, with 30-50,000 reads/cell.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007837","title":"Whole_Genome_Sequencing_PTALib__LCH_","description":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from Newcastle.","abstract":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from Newcastle.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007838","title":"Ultima_ppmSeq_WES__cord_blood_","description":"This study is to explore the sequencing data produced by the Ultima ppmSeq system. The purpose of this study is to identify the error profiles using whole exome sequencing of ultra-low mutation burden samples (cord blood). The result of this will be the development of a mask to filter out common artefactual mutations and sites. This is a high priority in the department given the significant cost savings.","abstract":"The new implementation of NovaSeq X brings new error profiles. The purpose of this study is to identify the error profiles using whole exome sequencing of ultra-low mutation burden samples (cord blood). The result of this will be the development of a mask to filter out common artefactual mutations and sites. This is a high priority in the department given the significant cost savings.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007839","title":"Ultima_ppmSeq_WGS__cord_blood_","description":"This study is to explore the sequencing data produced by the Ultima ppmSeq system. The purpose of this study is to identify the error profiles using whole genome sequencing of ultra-low mutation burden samples (cord blood). The result of this will be the development of a mask to filter out common artefactual mutations and sites. This is a high priority in the department given the significant cost savings.","abstract":"The new implementation of NovaSeq X brings new error profiles. The purpose of this study is to identify the error profiles using whole exome sequencing of ultra-low mutation burden samples (cord blood). The result of this will be the development of a mask to filter out common artefactual mutations and sites. This is a high priority in the department given the significant cost savings.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007840","title":"Tyrol Lifestyle Atlas: Intermittent Fasting Methylation Data","description":"This study explored methylation, clinical, and other molecular alterations longitudinally over the course of intermittent fasting in healthy women aged 30 to 60. Here, we present methylation data from three matched sample types - buccal, cervical, and blood - longitudinally over the course of six months (baseline, month 2, month 4, and month 6).","abstract":"This study explored methylation, clinical, and other molecular alterations longitudinally over the course of intermittent fasting in healthy women aged 30 to 60. Here, we present methylation data from three matched sample types - buccal, cervical, and blood - longitudinally over the course of six months (baseline, month 2, month 4, and month 6).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-06-13T09:15:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007841","title":"Tyrol Lifestyle Atlas: Smoking Cessation Methylation Data","description":"This study explored methylation, clinical, and other molecular alterations longitudinally over the course of smoking cessatio in healthy women aged 30 to 60. Here, we present methylation data from three matched sample types - buccal, cervical, and blood - longitudinally over the course of six months (baseline, month 2, month 4, and month 6).","abstract":"This study explored methylation, clinical, and other molecular alterations longitudinally over the course of smoking cessatio in healthy women aged 30 to 60. Here, we present methylation data from three matched sample types - buccal, cervical, and blood - longitudinally over the course of six months (baseline, month 2, month 4, and month 6).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-06-13T09:21:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007842","title":"Tyrol Lifestyle Atlas: Intermittent Fasting 16s Microbiome Data","description":"This study explored 16s microbiome, clinical, and other molecular alterations longitudinally over the course of intermittent fasting in healthy women aged 30 to 60. Here, we present 16s microbiome data from two matched sample types - saliva and faecal (baseline, month 2, month 4, and month 6).","abstract":"This study explored 16s microbiome, clinical, and other molecular alterations longitudinally over the course of intermittent fasting in healthy women aged 30 to 60. Here, we present 16s microbiome data from two matched sample types - saliva and faecal (baseline, month 2, month 4, and month 6).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007843","title":"Tyrol Lifestyle Atlas: Smoking Cessation 16s Microbiome Data","description":"This study explored 16s microbiome, clinical, and other molecular alterations longitudinally over the course of smoking cessation in healthy women aged 30 to 60. Here, we present 16s microbiome data from two matched sample types - saliva and faecal (baseline, month 2, month 4, and month 6).","abstract":"This study explored 16s microbiome, clinical, and other molecular alterations longitudinally over the course of smoking cessation in healthy women aged 30 to 60. Here, we present 16s microbiome data from two matched sample types - saliva and faecal (baseline, month 2, month 4, and month 6).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-08-12T15:00:33.642042+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007844","title":"Array-based methylation analysis of SDHB-deficient pheochromocytoma and paraganglioma","description":null,"abstract":null,"study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-06-14T04:20:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007845","title":"WES__Prominent__oesophagus","description":"Oesophageal carcinoma incidence varies across the world.  We wish to investigate the reasons behind this using high depth sequencing of normal oesophageal epithelium.","abstract":"Oesophageal carcinoma incidence varies across the world.  We wish to investigate the reasons behind this using high depth sequencing of normal oesophageal epithelium.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007846","title":"Nanoseq__Prominent__oesophagus","description":"Oesophageal carcinoma incidence varies across the world.  We wish to investigate the reasons behind this using nanorate sequencing of normal oesophageal epithelium.","abstract":"Oesophageal carcinoma incidence varies across the world.  We wish to investigate the reasons behind this using nanorate sequencing of normal oesophageal epithelium.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007847","title":"GOSH_Paediatric_Tumour_23P134_WGS_Managed_Access","description":"ATRT/MRT Post mortem","abstract":"ATRT/MRT Post mortem","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007848","title":"HCA_Heart_Adult_Wellcome_spatial","description":"Spatial transcriptome analysis of the human heart","abstract":"Cell Atlas of the human heart The aim of this project is to profile human heart on a single-cell level. Cardiac human tissue will be sampled from adult donors and will be processed for 10X single cell and single nuclei RNA sequencing and spatial transcriptomics. This data is part of a pre-publication release.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-06-18T12:17:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007849","title":"Whole blood transcriptomic analysis in Rheumatoid arthritis-associated interstitial lung disease (RA-ILD)","description":"Whole blood RNA sequencing was performed longitudinally in 11 subjects with RA-ILD before starting major immunosuppression therapy. As control groups 7 healthy individuals and 9 subjects with rheumatoid arthritis were used. Differential expression analysis, pathway analysis and weighted gene co-expression network analysis were performed to identify gene expression signatures.","abstract":"Whole blood RNA sequencing was performed longitudinally in 11 subjects with RA-ILD before starting major immunosuppression therapy. As control groups 7 healthy individuals and 9 subjects with rheumatoid arthritis were used. Differential expression analysis, pathway analysis and weighted gene co-expression network analysis were performed to identify gene expression signatures.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007850","title":"Investigating Host Genetic Risk Factors for Tuberculosis in Highly Endemic South African Populations","description":"It is apparent from our recent population genetic and admixture mapping work 1–3 that a substantial part of the ancestral input into the South African Coloured (SAC) population is from the San or Khoe groups, which are not well represented in publicly available genetic databases. It is a reasonable assumption that the SAC population in the Western Cape may have derived more genetic input from the present KhoeSan population in the Northern Cape than the San residing in Namibia. It was concluded by our group that it is indeed the southern African KhoeSan group, the ≠Khomani, that best represent the KhoeSan contribution seen in the SAC 4. More recently, it has been shown that there are ancestry related increases in TB susceptibility, especially with increased Bantu-speaking African and KhoeSan ancestry 5. We aim to elucidate the epidemiological and human-host genetic risk factors for TB and the immunological pathways modulating TB infection.  \n\nThe proposed sub-study will enroll people evaluated for TB at Northern Cape community health clinics and their contacts from their households and/or community. We will conduct a demographic interview, collect saliva, which will be used for genetic analysis, and blood to determine latent TB infection status and capture immunological responses to mycobacterial infections at the cellular level and RNA sequencing.","abstract":"It is apparent from our recent population genetic and admixture mapping work 1–3 that a substantial part of the ancestral input into the South African Coloured (SAC) population is from the San or Khoe groups, which are not well represented in publicly available genetic databases. It is a reasonable assumption that the SAC population in the Western Cape may have derived more genetic input from the present KhoeSan population in the Northern Cape than the San residing in Namibia. It was concluded by our group that it is indeed the southern African KhoeSan group, the ≠Khomani, that best represent the KhoeSan contribution seen in the SAC 4. More recently, it has been shown that there are ancestry related increases in TB susceptibility, especially with increased Bantu-speaking African and KhoeSan ancestry 5. We aim to elucidate the epidemiological and human-host genetic risk factors for TB and the immunological pathways modulating TB infection.  \n\nThe proposed sub-study will enroll people evaluated for TB at Northern Cape community health clinics and their contacts from their households and/or community. We will conduct a demographic interview, collect saliva, which will be used for genetic analysis, and blood to determine latent TB infection status and capture immunological responses to mycobacterial infections at the cellular level and RNA sequencing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007851","title":"LCM_WES__adrenal_gland_","description":"Whole exome sequencing in adrenal glands from a number of donors, both healthy and with pathology.","abstract":"Investigating the driver landscape in adrenals, in both health and disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007852","title":"Profiling Chromatin Accessibility in Humans Using Adenine Methylation and Long-Read Sequencing","description":"This dataset includes raw nanopore, base-called, and 6mA frequency data for EcoGII-treated NA12878 and MCF7 chromatin samples. It also includes raw nanopore data for the HG002 EcoGII-treated DNA.","abstract":"This dataset includes raw nanopore, base-called, and 6mA frequency data for EcoGII-treated NA12878 and MCF7 chromatin samples. It also includes raw nanopore data for the HG002 EcoGII-treated DNA.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-06-19T18:17:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007853","title":"Exome_NanoSeq__Pancreatic_Islets_","description":"Exome NanoSeq in islets from pancreata from a number of donors, primarily those without a known malignancy. Samples may contain pre-malignant histology and may also come from those with non-malignant diseases of the pancreas, such as diabetes mellitus.","abstract":"Investigating the driver landscape across a large number of pancreatic islets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007854","title":"XClone for analyzing somatic copy number alterations","description":"Somatic copy number alterations (CNAs) are major mutations that contribute to the development and progression of various cancers. Despite a few computational methods proposed to detect CNAs from single-cell transcriptomic data, the technical sparsity of such data makes it challenging to identify allele-specific CNAs, particularly in complex clonal structures. In this study, we present a statistical method, XClone, that strengthens the signals of read depth and allelic imbalance by effective smoothing on cell neighborhood and gene coordinate graphs to detect haplotype-aware CNAs from scRNA-seq data. By applying XClone to multiple datasets with challenging compositions, we demonstrated its ability to robustly detect different types of allele-specific CNAs and potentially indicate whole genome duplication, therefore enabling the discovery of corresponding subclones and the dissection of their phenotypic impacts.","abstract":"Somatic copy number alterations (CNAs) are major mutations that contribute to the development and progression of various cancers. Despite a few computational methods proposed to detect CNAs from single-cell transcriptomic data, the technical sparsity of such data makes it challenging to identify allele-specific CNAs, particularly in complex clonal structures. In this study, we present a statistical method, XClone, that strengthens the signals of read depth and allelic imbalance by effective smoothing on cell neighborhood and gene coordinate graphs to detect haplotype-aware CNAs from scRNA-seq data. By applying XClone to multiple datasets with challenging compositions, we demonstrated its ability to robustly detect different types of allele-specific CNAs and potentially indicate whole genome duplication, therefore enabling the discovery of corresponding subclones and the dissection of their phenotypic impacts.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-06-25T03:07:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007855","title":"A GWAS study with the AlpeDPD study cohort","description":"A genome-wide association study (GWAS) with patients treated with fluoropyrimidines was performed to identify genetic variants linked to the severe fluoropyrimidine-related toxicity.","abstract":"A genome-wide association study (GWAS) with patients treated with fluoropyrimidines was performed to identify genetic variants linked to the severe fluoropyrimidine-related toxicity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-07-02T08:06:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007856","title":"Li_Fraumeni_Syndrome_Inheritance_and_Tumourigenesis___TargetedDupSeq_","description":"This work aim to study clonal dynamics of pathogenic mutations in male germline. Using Nanoseq method, sperm from normal panel will be compared with sperm from men who have either clinical phynotypes or they have child(ren) with germline predisposition syndromes.","abstract":"Inherited cancers play a major role in about 5 to 10 percent of all cancers. It is increasingly apparent that many inherited cancer syndromes arise through new mutations acquired most likely in germline of fathers. Most of the burden of high-penetrance germline predisposition to cancer arises through mutations acquired during spermatogenesis. However, little is known about mutagenesis within the hierarchy of spermatogenesis or factors that influence rates of mutation in the testes. It is likely that mutations in spermatogonia stem cells that confer weaker selective advantage and generate smaller clonal expansions in the testes, become enrich in sperms and transmit to the next generations. However, due to the low sensitivity of standard genomic approaches, subclonal mutations that may only be present in small contiguous areas within testes have been poorly investigated. This proposal aims to measure the mutational burden of pathogenic variants in sperms and to identify the processes that underlie their acquisition","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007857","title":"RNA sequencing of lung fibroblasts","description":"RNA sequencing of lung fibroblasts","abstract":"RNA sequencing of lung fibroblasts","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007858","title":"Pancreas_phylogenetics_NovaSeq_X_EMSeq__dual_WGS_EMSeq_","description":"Exploring phylogenetics within pancreas samples from health and disease. This study is related to the enzymatic methylation sequencing component.","abstract":"Exploring phylogenetics within pancreas samples from health and disease. This study is related to the enzymatic methylation sequencing component.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007859","title":"Pancreas_phylogenetics_NovaSeq_X_WGS__dual_WGS_EMSeq_","description":"Exploring phylogenetics within pancreas samples from health and disease. This study is related to the whole genome component.","abstract":"Exploring phylogenetics within pancreas samples from health and disease. This study is related to the whole genome component.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007860","title":"LCM_WGS___Skin_with_or_without_inflammatory_skin_disease","description":"Whole genome sequencing through the low-input DNA pipeline of skin samples. Tissue will be processed either from laser capture microdissection. Insights will be gained here directly from the sequencing but also from using the data as a matched normal in Exome LCM-B or nanoseq. Skin samples will be obtained from patients with and without chronic inflammatory skin disease.","abstract":"Investigating the driver landscape and mutational processes across diverse cell types in the skin with or without chronic skin inflammatory diseases.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007861","title":"Clonal_dynamics_and_selective_pressures_of_haematopoietic_stem_cell_transplant","description":"This study will involve WGS of single-cell derived colonies from related age-mismatched transplant recipients and donors, followed by phylogeny reconstruction and analysis.","abstract":"Haematopoietic stem cell transplant (HSCT) is a vital life-saving treatment that remains the only curative option for many patients with haematological malignancies and inherited bone marrow disorders.  However, significant morbidity and mortality of the treatment remain a major problem, and better understanding of the biology of HSCT is a major goal as a means of improving outcomes. This project is focussed on two aspects of understanding HSCT.\n\n(1)\tSelective pressures during HSCT\nPrevious work suggests that exaggerated/ altered selective pressures during the HSCT procedure play a major role in shaping the clonal landscape in the recipient, leading to an increased ‘oligoclonality’ compared to recipients. However, the components of the complex transplant procedure during which these pressures operate is unclear. For example, they may operate at the time of cell mobilization, cell manipulation, cryopreservation, engraftment or the time of post-transplant complications. By looking for evidence of selection on different genes at various points during the transplant procedure, and in patients who have experienced different transplant protocols, we hope to better understand the timing and nature of this selection.\n\n(2)\tImpact of cell intrinsic factors vs bone marrow environment on the clonal landscape of ageing blood\nRecent work has demonstrated that with increasing age there is a trend towards oligoclonality of the haematopoietic system, with the emergence of a number of dominant clones.  In some cases, clonal evolution may eventually result in haematological malignancies.  However, the degree to which cell intrinsic vs cell extrinsic mechanisms (e.g. the bone marrow microenvironment) shape this trend is unclear.  The performance of age-mismatched allogeneic HSCT provides a unique opportunity to understand the relative importance of these factors. For example, in some cases HSCs from very young donors are transplanted into elderly recipients, and in some cases, HSCs from elderly donors are transplanted into young recipients.  In such cases, the bone marrow microenvironment will remain that of the recipient, while the cell intrinsic factors will reflect those of the donor.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007862","title":"Exome_NanoSeq__FFPE_thyroid_","description":"Exploring the driver landscape in thyroids fixed in formalin, in health and disease.","abstract":"Exploring the driver landscape in thyroids fixed in formalin, in health and disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007863","title":"Targeted_NanoSeq__FFPE_thyroid_","description":"Exploring the driver landscape in thyroids fixed in formalin, in health and disease.","abstract":"Exploring the driver landscape in thyroids fixed in formalin, in health and disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007864","title":"Stratton__LCMB_FFPE_studies_RCC","description":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. \n\nThis pilot study will investigate opportunities for detecting mutational signatures in samples fixed in formalin and embedded in paraffin (FFPE) for variable lengths of time.","abstract":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. \n\nThis pilot study will investigate opportunities for detecting mutational signatures in samples fixed in formalin and embedded in paraffin (FFPE) for variable lengths of time.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007865","title":"Stratton__LCMB_FFPE_studies_CRC","description":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. \n\nThis pilot study will investigate opportunities for detecting mutational signatures in samples fixed in formalin and embedded in paraffin (FFPE) for variable lengths of time.","abstract":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. \n\nThis pilot study will investigate opportunities for detecting mutational signatures in samples fixed in formalin and embedded in paraffin (FFPE) for variable lengths of time.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007866","title":"Pharmacogenomic Analysis Reveals New Therapeutic Options for Pleural Mesothelioma","description":"Background: Pleural mesothelioma (PM) urgently requires novel effective treatments. Drug repurposing is a relevant strategy to discover new therapeutic options among well-known drugs used in clinical practice. This study aimed to identify new therapies in the context of molecular heterogeneity of PM.\nMethods: We performed a multi-omics study of the largest cohort of patient-derived primary PM cell lines (n=58) to date, using whole exome sequencing, RNA sequencing and methylome analysis. We also conducted a large-scale drug screening of over 1300 compounds on a subset of cell lines (n=11), as well as an extension screen (n=48) for selected drugs of interest. The best candidates were validated using 3D culture and mouse models. \n Results: We demonstrated that the molecular landscape of the cell lines cohort recapitulates the main findings in tumours and revealed new specific features of PM. The large-scale drug screening and subsequent validations highlighted notably strong sensitivity to entinostat and fluvastatin. Importantly, both compounds displayed same efficacy in 2D and 3D culture models and single treatment prolonged survival in vivo similarly or even better than standard chemotherapy. Strikingly, combining entinostat treatment with anti-PD1 led to cures in some mice and immunized them against tumour cells.\nConclusions: Among several candidates, we identified entinostat, notably in combination with immune checkpoint inhibitor, and to a lesser extent fluvastatin, as promising therapeutic options for patients. We believe our study provides a valuable resource that could contribute to advances in the field and warrants further clinical investigation.","abstract":"Background: Pleural mesothelioma (PM) urgently requires novel effective treatments. Drug repurposing is a relevant strategy to discover new therapeutic options among well-known drugs used in clinical practice. This study aimed to identify new therapies in the context of molecular heterogeneity of PM.\nMethods: We performed a multi-omics study of the largest cohort of patient-derived primary PM cell lines (n=58) to date, using whole exome sequencing, RNA sequencing and methylome analysis. We also conducted a large-scale drug screening of over 1300 compounds on a subset of cell lines (n=11), as well as an extension screen (n=48) for selected drugs of interest. The best candidates were validated using 3D culture and mouse models. \n Results: We demonstrated that the molecular landscape of the cell lines cohort recapitulates the main findings in tumours and revealed new specific features of PM. The large-scale drug screening and subsequent validations highlighted notably strong sensitivity to entinostat and fluvastatin. Importantly, both compounds displayed same efficacy in 2D and 3D culture models and single treatment prolonged survival in vivo similarly or even better than standard chemotherapy. Strikingly, combining entinostat treatment with anti-PD1 led to cures in some mice and immunized them against tumour cells.\nConclusions: Among several candidates, we identified entinostat, notably in combination with immune checkpoint inhibitor, and to a lesser extent fluvastatin, as promising therapeutic options for patients. We believe our study provides a valuable resource that could contribute to advances in the field and warrants further clinical investigation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-07-11T14:20:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007867","title":"Nanoseq__Zambia__oesophagus","description":"Oesophageal carcinoma incidence varies across the world.  We wish to investigate the reasons behind this using nanorate sequencing of normal oesophageal epithelium from Zambia an area of particularly high incidence.","abstract":"Oesophageal carcinoma incidence varies across the world.  We wish to investigate the reasons behind this using nanorate sequencing of normal oesophageal epithelium from Zambia an area of particularly high incidence.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007868","title":"UV_treatment_Bl6_and_Albino_mice___Nanoseq","description":"We wish to investigate the mutational landscape in albino and bl6 mice when exposed to UV light.","abstract":"We wish to investigate the mutational landscape in albino and bl6 mice when exposed to UV light.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007869","title":"Families_Affected_by_Rare_Developmental_Disorders_WGS","description":"This work aims to study transmission of pathogenic mutations using trio WGS of DNA provided by families with a child with a developmental disorder caused by a de novo mutation.","abstract":"As men age, the risk of pathogenic mutations in sperm increases, elevating the chances of having a child with a developmental disorder or cancer syndrome. With rising parental ages, the incidence of such disorders in children is growing. This work aims to study transmission of pathogenic mutations using long read sequencing of DNA provided by families with a child with a developmental disorder caused by a de novo mutation.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-07-16T15:27:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007870","title":"Somatic_mutation_and_clonal_evolution_in_the_pancreas_NovaSeq_X__WGS_","description":"Investigating the somatic mutation landscape in normal, diseased and pre-malignant pancreatic tissue.","abstract":"Investigating the somatic mutation landscape in normal, diseased and pre-malignant pancreatic tissue.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007871","title":"Somatic_mutational_landscape_in_individuals_with_germline_cancer_predisposition_WGS","description":"This work aims to study the somatic impact, in normal and malignant tissues, of varying germline cancer predisposition syndromes.","abstract":"A multitude pathogenic germline variants are known to cause a broad spectrum of cancer predispostion. The underlying mechanism that leads to variable penetrance and expressivity associated with these variants, in a tissue specific manner, is poorly understood. Using serially sampled specimens from individuals with different underlying germline predisposition to cancer, we aim to elucidate the underlying somatic mutational landscape and clonal dynamics that explain the wide spectrum of clinical phenotype.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-07-16T18:26:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007872","title":"Somatic_mutational_landscape_in_individuals_with_germline_cancer_predisposition_DupSeq","description":"This work aims to study the somatic impact, in normal and malignant tissues, of varying germline cancer predisposition syndromes.","abstract":"A multitude pathogenic germline variants are known to cause a broad spectrum of cancer predisposition. The underlying mechanism that leads to variable penetrance and expressivity associated with these variants, in a tissue specific manner, is poorly understood. Using serially sampled specimens from individuals with different underlying germline predisposition to cancer, we aim to elucidate the underlying somatic mutational landscape and clonal dynamics that explain the wide spectrum of clinical phenotype.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007873","title":"PD-L1 blockade immunotherapy rewires cancer-induced emergency myelopoiesis","description":"Introduction\nImmune checkpoint blockade (ICB) immunotherapy has revolutionized cancer treatment, demonstrating exceptional clinical responses in a wide range of cancers. Despite the success, a significant proportion of patients still fail to respond, highlighting the existence of unappreciated mechanisms of immunotherapy resistance. Delineating such mechanisms is paramount to minimize immunotherapy failures and optimize the clinical benefit.\nMethods\n In this study, we treated tumour-bearing mice with PD-L1 blockage antibody (aPD-L1) immunotherapy, to investigate its effects on cancer-induced emergency myelopoiesis, focusing on bone marrow HSPCs. We examined the impact of aPD-L1 treatment on HSPC quiescence, proliferation, transcriptomic profile, and functionality.\nResults\nHerein, we reveal that aPD-L1 in tumour-bearing mice targets the hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (ΒΜ), mediating their exit from quiescence and promoting their proliferation. Notably, disruption of the PDL1/PD1 axis induces transcriptomic reprogramming in HSPCs, observed in both individuals with Hodgkin lymphoma (HL) and tumour-bearing mice, shifting towards an inflammatory state. Furthermore, HSPCs from aPDL1-treated mice demonstrated resistance to cancer-induced emergency myelopoiesis, evidenced by a lower generation of MDSCs compared to control-treated mice.\n Discussion:\nOur findings shed light on unrecognized mechanisms of action of ICB immunotherapy in cancer, which involves targeting of BM-driven HSPCs and reprogramming of cancer-induced emergency myelopoiesis.","abstract":"Introduction\nImmune checkpoint blockade (ICB) immunotherapy has revolutionized cancer treatment, demonstrating exceptional clinical responses in a wide range of cancers. Despite the success, a significant proportion of patients still fail to respond, highlighting the existence of unappreciated mechanisms of immunotherapy resistance. Delineating such mechanisms is paramount to minimize immunotherapy failures and optimize the clinical benefit.\nMethods\n In this study, we treated tumour-bearing mice with PD-L1 blockage antibody (aPD-L1) immunotherapy, to investigate its effects on cancer-induced emergency myelopoiesis, focusing on bone marrow HSPCs. We examined the impact of aPD-L1 treatment on HSPC quiescence, proliferation, transcriptomic profile, and functionality.\nResults\nHerein, we reveal that aPD-L1 in tumour-bearing mice targets the hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (ΒΜ), mediating their exit from quiescence and promoting their proliferation. Notably, disruption of the PDL1/PD1 axis induces transcriptomic reprogramming in HSPCs, observed in both individuals with Hodgkin lymphoma (HL) and tumour-bearing mice, shifting towards an inflammatory state. Furthermore, HSPCs from aPDL1-treated mice demonstrated resistance to cancer-induced emergency myelopoiesis, evidenced by a lower generation of MDSCs compared to control-treated mice.\n Discussion:\nOur findings shed light on unrecognized mechanisms of action of ICB immunotherapy in cancer, which involves targeting of BM-driven HSPCs and reprogramming of cancer-induced emergency myelopoiesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-07-18T10:11:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007874","title":"HSC_population_dynamics_in_perturbation___80M1_samples___WGMS","description":"The aim of this project is to characterise how the systemic environment shapes the clonal landscape in adult humans and how perturbations affect this landscape. In collaboration with Dr George Follows at Addenbrooke’s, we have collected longitudinal samples from patients before and after chemotherapy, and performed whole genome sequencing on their hematopoietic stem cells (HSCs). Using patterns of shared and unique mutations, we constructed phylogenetic trees of each patient’s HSCs. We now also wish to perform whole genome methylation sequencing to understand whether methylation changes accompany clonal expansions occuring in perturbation. \nThe main questions I intend to address are:\n1. Are methylation changes that gave some HSCs an advantage, which resulted in their clonal expansion, still advantageous in the new environment? Does chemotherapy favour some methylation changes over others? \n2. How do chemotherapies of different intensities affect the clonal landscape of HSCs? \n3. How does ageing affect the ability of the hematopoietic system to recover after chemotherapy? Are any clinical variables associated with improved recovery? \n4. Does the population of HSCs remain unchanged? \n5. How do different chemotherapies contribute to (methylation) mutagenesis of HSCs? \n6. Are any methylation changes present in cells which do not have a driver mutation, yet they proliferate at an accelerated pace?","abstract":"Background\n\nWith age, somatic mutations accumulate in normal dividing cells, including hematopoietic stem cells (HSCs). It appears that some mutations provide HSCs with a fitness advantage, allowing their mutant daughter blood cells to disproportionately expand (Jaiswal &amp; Ebert, 2019). The phenomenon is termed clonal hematopoiesis (CH) and it is associated with ageing as well as hematologic malignancies, cardiovascular disease and all-cause mortality (Genovese et al., 2014; Jaiswal &amp; Ebert, 2019). Preliminary evidence suggests that after a perturbation such as cancer therapy, the composition of clones, which dominate the hematopoietic system, changes (Bolton, 2020). However, the studies carried out until now have analysed CH at the population level, but little is known about the process at an individual level. Moreover, no study until now has addressed how perturbations of the systemic environment affect the clonal composition of blood at the single-cell level.\nMethods\n\nMy study proposes to investigate haematopoietic stem cell dynamics in 4 groups of individuals:\n1.\tYounger adults (younger than 55) who have been diagnosed with diffuse large B-cell lymphoma (DLBCL) and will be treated with R-CHOP\n2.\tOlder adults (older than 70 years) who have been diagnosed with DLBCL and will be treated with R-CHOP or R-mini-CHOP\n3.\tYounger adults who have been diagnosed with Hodgkin’s lymphoma (a more aggressive lymphoma than DLBCL) and will be receiving BEACOPP or ABVD (a chemotherapy treatment that is more aggressive than R-CHOP)\n4.\tA normal, healthy adult individual to serve as control.\n\nFor these experiments, the initial sample is between 100 and 200 single cell-derived HSC colonies per time point, which will be obtained from each individual’s peripheral blood.  I aim to ‘phenotype’ the colonies in a number of ways.   Firstly, I will track the growth rate and size of each colony.  Secondly, I will phenotype the spectrum of individual cells produced in each colony.  Thirdly, I will assay colony response to in vitro perturbations, such as chemotherapy and elevated oxygen levels (which result in increased levels of reactive oxygen species).  Fourthly, I will assess variability at the methylation level. \n\nThe colonies will then undergo whole genome sequencing to a depth of 10x (given that colonies are single cell-derived, this is adequate coverage for calling mutations, especially those shared by more than one colony). Somatic mutations, are then called by the Shearwater algorithm. From patterns of shared and unique mutations across the colonies, I will reconstruct the phylogenetic tree underpinning the clonal relationships of the cells identified.  From the pattern of branch points (coalescences), which represent symmetric HSC divisions, phylodynamic models can be used to estimate the size of the total HSC pool from which the cells are derived. Furthermore, the combined phylogeny of each individual’s pre- and post-chemotherapy samples allows one to compare and contrast clades which are expanding or diminishing with the perturbation. We will also be able to identify any variation in mutation rates and signatures over the human lifespan.\n\nFor a subset of samples, we will undertake whole genome methylation sequencing on a number of cells from each colony. Knowing the cells' phylogeny, we will be able to find heritable methylation changes and understand if they enable clonal expansion (of particular interest for driverless clones) as well as whether rate of methylation change increases during chemotherapy.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007875","title":"Whole_Genome_Sequencing_PTALib__CML_Transformation_","description":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from CBSB.","abstract":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from CBSB.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007876","title":"DNA methylation of Odontogenic myxoma","description":"Odontogenic myxoma is a rare, benign and locally aggressive tumor that develops in the tooth-bearing regions of the jaw. The molecular mechanisms underlying odontogenic myxomas are unknown and no diagnostic markers are available so far. The aim of this study was to analyze DNA methylation and copy number alterations in odontogenic myxomas to identify new molecular signatures for diagnostic decision-making.","abstract":"Odontogenic myxoma is a rare, benign and locally aggressive tumor that develops in the tooth-bearing regions of the jaw. The molecular mechanisms underlying odontogenic myxomas are unknown and no diagnostic markers are available so far. The aim of this study was to analyze DNA methylation and copy number alterations in odontogenic myxomas to identify new molecular signatures for diagnostic decision-making.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007877","title":"Metabolic profiling of patient-derived organoids reveals nucleotide synthesis as a metabolic vulnerability in malignant rhabdoid tumors","description":"Malignant rhabdoid tumor (MRT) is one of the most aggressive childhood cancers for which no effective treatment options are available. Reprogramming of cellular metabolism is an important hallmark of cancer, with various metabolism-based drugs being approved cancer treatment. In this study, we use patient derived tumor organoids (tumoroids) to map the metabolic landscape of several pediatric cancers. Combining gene expression analyses and metabolite profiling using mass spectrometry, we find nucleotide biosynthesis to be a particular vulnerability of MRT. Treatment of MRT tumoroids with de novo nucleotide synthesis inhibitors lowers nucleotide levels in MRT tumoroids and induces apoptosis. Lastly, we demonstrate invivo efficacy of methotrexate in an MRT PDX mouse model. Our study revealsnucleotide biosynthesis as an MRT-specific metabolic vulnerability, which can ultimately lead to better treatment options for children suffering from this lethal pediatric malignancy.","abstract":"Malignant rhabdoid tumor (MRT) is one of the most aggressive childhood cancers for which no effective treatment options are available. Reprogramming of cellular metabolism is an important hallmark of cancer, with various metabolism-based drugs being approved cancer treatment. In this study, we use patient derived tumor organoids (tumoroids) to map the metabolic landscape of several pediatric cancers. Combining gene expression analyses and metabolite profiling using mass spectrometry, we find nucleotide biosynthesis to be a particular vulnerability of MRT. Treatment of MRT tumoroids with de novo nucleotide synthesis inhibitors lowers nucleotide levels in MRT tumoroids and induces apoptosis. Lastly, we demonstrate invivo efficacy of methotrexate in an MRT PDX mouse model. Our study revealsnucleotide biosynthesis as an MRT-specific metabolic vulnerability, which can ultimately lead to better treatment options for children suffering from this lethal pediatric malignancy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-07-23T10:15:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007878","title":"WES__Investigating_the_clonal_dynamics_in_interstitial_lung_diseases_using_laser_captured_microdissection","description":"This study aims to characterise the mutational landscape and identify driver mutations in interstitial lung diseases (ILDs) including idiopathic pulmonary fibrosis, seccondary pulmonary fibrosis overlapping with autoimmune conditions as well as stage IV sarcoidosis. Here, we will perform laser-captured microdissection and generate WES data with fresh frozen bronchus and lung parenchymal tissues from patients with ILDs in order to better understand the mutational processes in these diseases.","abstract":"This study aims to characterise the mutational landscape and identify driver mutations in interstitial lung diseases (ILDs) including idiopathic pulmonary fibrosis, seccondary pulmonary fibrosis overlapping with autoimmune conditions as well as stage IV sarcoidosis. Here, we will perform laser-captured microdissection and generate WES data with fresh frozen bronchus and lung parenchymal tissues from patients with ILDs in order to better understand the mutational processes in these diseases.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007879","title":"Somatic_mutational_landscape_in_individuals_with_germline_cancer_predisposition_Targeted","description":"his work aims to study the somatic impact, in normal and malignant tissues, of varying germline cancer predisposition syndromes.","abstract":"A multitude pathogenic germline variants are known to cause a broad spectrum of cancer predispostion. The underlying mechanism that leads to variable penetrance and expressivity associated with these variants, in a tissue specific manner, is poorly understood. Using serially sampled specimens from individuals with different underlying germline predisposition to cancer, we aim to elucidate the underlying somatic mutational landscape and clonal dynamics that explain the wide spectrum of clinical phenotype.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007880","title":"Sjogren_s_scRNA_project","description":"The study aims at understanding the functional consequences of Sjogren's syndrome driver mutations at single cell resolution","abstract":"Sjogren’s Disease(SjD) is a systemic autoimmune disease characterized by exocrine dysfunction.  It involves gene microenvironment interactions leading to infiltration of immune cells, however its pathogenesis and the mechanisms driving exocine dysfunction remain to be understood. The aim of the project is to identity the mutations in resident immune cells of SJD patients and how those impact immune epithelial cell crosstalks and tissue dysfunction","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007881","title":"DERMATLAS__Hobnail_hemangioma_WES","description":"IVirtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Hobnail hemangiomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Hobnail hemangiomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007882","title":"DERMATLAS__Hobnail_hemangioma_RNAseq","description":"IVirtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Hobnail hemangiomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Hobnail hemangiomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007883","title":"Dermatlas__Perineuroma_Wes","description":"IVirtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Perineuromas.","abstract":"IVirtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Perineuromas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007884","title":"Dermatlas__Perineuroma_RNAseq","description":"IVirtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Perineuromas.","abstract":"IVirtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Perineuromas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007885","title":"DERMATLAS__Malignant_mxed_tumour_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are: malignant mixed tumour.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are: malignant mixed tumour.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007886","title":"WGS of eHHV-6B-positive Japanese","description":"Short-read WGS datasets of 15 eHHV-6B-positive Japanese subjects (Illumina WGS) and long-read WGS datasets of 3 eHHV-6B-positive Japanese subjects with SLE (PacBio 30x HiFi long-read sequencing).","abstract":"Short-read WGS datasets of 15 eHHV-6B-positive Japanese subjects (Illumina WGS) and long-read WGS datasets of 3 eHHV-6B-positive Japanese subjects with SLE (PacBio 30x HiFi long-read sequencing).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-07-30T08:28:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007887","title":"Autoimmune_liver_disease_exome_targeted_nanoseq","description":"Whole Exome and Targeted NanoSeq of autoimmune liver disease (AIH/PBC/PSC) samples.","abstract":"Part of the development of the chronic liver disease somatic mutational atlas - studying the adaptive mutational pathways developed by hepatocytes on their path towards end-stage liver disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007888","title":"Wilson_disease_exome_targeted_nanoseq","description":"Whole Exome and Targeted NanoSeq of Wilson disease samples.","abstract":"Part of the development of the chronic liver disease somatic mutational atlas - studying the adaptive mutational pathways developed by hepatocytes on their path towards end-stage liver disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007889","title":"Neuroblastoma_Cambridge_Behjati_WellcomeCore_WGS","description":"High-risk neuroblastoma is treated with intensive chemotherapy, and most patients will receive myeloablative therapy followed by an autologous stem cell transplant. Survivors have a 100-fold risk of developing acute myeloid leukaemia within the 10 years that follow relative to the general population. Our study will investigate at high resolution the effects of chemotherapy on the bone marrow for one child with high-risk neuroblastoma. Single cell derived blood colonies from both before and after treatment have been cultured and will be sequenced, allowing us to determine the mutations at the single cell level before and after chemotherapy, and to quantify effects of chemotherapy on the clonal dynamics of the haematopoietic stem cell pool.’ Whole Genome Study.","abstract":"High-risk neuroblastoma is treated with intensive chemotherapy, and most patients will receive myeloablative therapy followed by an autologous stem cell transplant. Survivors have a 100-fold risk of developing acute myeloid leukaemia within the 10 years that follow relative to the general population. Our study will investigate at high resolution the effects of chemotherapy on the bone marrow for one child with high-risk neuroblastoma. Single cell derived blood colonies from both before and after treatment have been cultured and will be sequenced, allowing us to determine the mutations at the single cell level before and after chemotherapy, and to quantify effects of chemotherapy on the clonal dynamics of the haematopoietic stem cell pool.’ Whole Genome Study.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007890","title":"Neuroblastoma_Cambridge_Behjati_WellcomeCore_EMseq","description":"High-risk neuroblastoma is treated with intensive chemotherapy, and most patients will receive myeloablative therapy followed by an autologous stem cell transplant. Survivors have a 100-fold risk of developing acute myeloid leukaemia within the 10 years that follow relative to the general population. Our study will investigate at high resolution the effects of chemotherapy on the bone marrow for one child with high-risk neuroblastoma. Single cell derived blood colonies from both before and after treatment have been cultured and will be sequenced, allowing us to determine the mutations at the single cell level before and after chemotherapy, and to quantify effects of chemotherapy on the clonal dynamics of the haematopoietic stem cell pool.’ Whole Genome Study.","abstract":"High-risk neuroblastoma is treated with intensive chemotherapy, and most patients will receive myeloablative therapy followed by an autologous stem cell transplant. Survivors have a 100-fold risk of developing acute myeloid leukaemia within the 10 years that follow relative to the general population. Our study will investigate at high resolution the effects of chemotherapy on the bone marrow for one child with high-risk neuroblastoma. Single cell derived blood colonies from both before and after treatment have been cultured and will be sequenced, allowing us to determine the mutations at the single cell level before and after chemotherapy, and to quantify effects of chemotherapy on the clonal dynamics of the haematopoietic stem cell pool.’ EMseq study.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007891","title":"Phosphoproteomics adds value to treatment recommendations in molecular tumor boards","description":"Precision oncology approaches employing genomics-guided targeted therapies for individual patients have provided significant survival benefits in several cancer types. However, low response rates in most solid malignancies, many patients without actionable genomic lesions, and increasing evidence that non-genomic mechanisms may play an important role in tumors indicate that genomics alone is often insufficient to inform and guide the clinical care of patients. Here, we show for the first time that comprehensive (phospho)proteome profiling is feasible and informative in a real-world prospective precision oncology setting. We developed a novel tumor pathway activity (TUPAC) scoring methodology that provides a holistic perspective on dysregulated receptor tyrosine kinase (RTK) signaling in individual patients. Based on 919 tumor tissue profiles of patients enrolled in the national NCT/DKTK MASTER study and the INFORM registry trial, we illustrate how TUPAC scoring can be used to uncover individual tumor biology in rare cancers and demonstrate that TUPAC methodology identifies EGFR-driven sarcomas despite the absence of genetic EGFR alterations. Overall, our work demonstrates the utility of the additional phosphoproteome data layer to enhance therapeutic recommendations in molecular tumor boards.","abstract":"Precision oncology approaches employing genomics-guided targeted therapies for individual patients have provided significant survival benefits in several cancer types. However, low response rates in most solid malignancies, many patients without actionable genomic lesions, and increasing evidence that non-genomic mechanisms may play an important role in tumors indicate that genomics alone is often insufficient to inform and guide the clinical care of patients. Here, we show for the first time that comprehensive (phospho)proteome profiling is feasible and informative in a real-world prospective precision oncology setting. We developed a novel tumor pathway activity (TUPAC) scoring methodology that provides a holistic perspective on dysregulated receptor tyrosine kinase (RTK) signaling in individual patients. Based on 919 tumor tissue profiles of patients enrolled in the national NCT/DKTK MASTER study and the INFORM registry trial, we illustrate how TUPAC scoring can be used to uncover individual tumor biology in rare cancers and demonstrate that TUPAC methodology identifies EGFR-driven sarcomas despite the absence of genetic EGFR alterations. Overall, our work demonstrates the utility of the additional phosphoproteome data layer to enhance therapeutic recommendations in molecular tumor boards.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-08-05T14:16:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007892","title":"HCA_Commercial_iPSCS_PBMCs_Haniffa_RNA","description":"Single cell sequencing of skin organoids derived from commercial iPSCS with introduced PBMCs\n\n","abstract":"This project uses so-called molecular barcodes (LARRY barcodes) to track how all the different cell types in human skin arise from stem cells. The overall project goals are to (i) gain a deeper understanding of skin development, (ii) establish models to study a variety of skin diseases, and (iii) provide a new powerful platform for the discovery of new therapeutics.\n","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007893","title":"Whole_Genome_Sequencing_PTALib__AA_","description":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from CBSB.","abstract":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from CBSB.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007894","title":"WGS_PNH_blood_colonies","description":"Exploration of the somatic and methylation landscape of PNH. Samples have been sourced from Leeds","abstract":"Exploration of the somatic and methylation landscape of PNH. Samples have been sourced from Leeds","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007895","title":"WGMS_PNH_blood_colonies","description":"Exploration of the somatic and methylation landscape of PNH. Samples have been sourced from Leeds","abstract":"Exploration of the somatic and methylation landscape of PNH. Samples have been sourced from Leeds","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007896","title":"Somatic_mutations_in_the_pancreas__LCM_RE_NanoSeq_neats_","description":"Matched normals required for investigating the mutation burden and mutational signatures in normal, diseased, and pre-malignant pancreatic tissue.","abstract":"Matched normals required for investigating the mutation burden and mutational signatures in normal, diseased, and pre-malignant pancreatic tissue.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007897","title":"HCA_Kidney_Adult_Perfusion_Wellcome_RNA_Managed_Access","description":"A response cell atlas of the human kidney","abstract":"The parenchymal cells of the kidney and tissue resident immune cells together mount responses to immune challenges and initiators of disease. These responses may spatially zonated within the organ and context specific. In this project, we perform normothermic normoxic machine perfusion, and challenge the kidney using specific perturbations. By interrogating the responses to stimulation with disease-relevant perturbations using single cell and spatial genomics methods, we aim to generate an atlas of cell type specific response states and the patterns of spatiotemporal regulation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007898","title":"Childhood_Cancer_Paediatric_Behjati_SRF_WGS_Nanoseq_Managed_Access","description":"An exploratory study using WGS NanoSeq on a bait set of common paediatric cancer genes and cancer predisposition genes to assess mutations, mutational signatures, treatment effect, risk of relapse and to study the development of childhood cancer.","abstract":"An exploratory study using WGS NanoSeq on a bait set of common paediatric cancer genes and cancer predisposition genes to assess mutations, mutational signatures, treatment effect, risk of relapse and to study the development of childhood cancer.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-08-12T17:17:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007899","title":"The University of Hong Kong Intestinal Metaplasia Organoids Study","description":"Background: Gastric intestinal metaplasia (IM) is a pre-cancerous stage spanning   a morphological spectrum that is poorly represented by human cell line models.\nObjective: We aim to establish and characterize human IM cell models to better understand IM progression along the cancer spectrum.\nDesign: A large human gastric IM organoid (IMO) cohort (n=28), their clonal derivatives and normal gastric organoids (n=42) for comparison were established. Comprehensive multi-omics profiling and functional characterization were performed.\nResults: Single-cell transcriptomes revealed IMO cells spanning a spectrum from hybrid gastric/intestinal to advanced intestinal differentiation. Their lineage trajectories connected different cycling and quiescent stem and progenitors, highlighting differences in gastric to IM transition and the potential origin of IM from STMN1 cycling isthmus stem cells. Hybrid IMOs showed impaired differentiation potential, high lineage plasticity beyond gastric or intestinal fates, and reactivation of a fetal gene program. \nCell populations in gastric IM and cancer tissues were highly similar to those derived from IMOs and exhibited a fetal signature. Genomically, IMOs showed elevated mutation burden, frequent chromosome 20 gain, and epigenetic de-regulation of many intestinal and gastric genes. Functionally, IMOs were FGF10 independent and showed downregulated FGFR2. Several IMOs exhibited a cell-matrix adhesion independent (CMi) subpopulation that displayed chromosome 20 gain but lacked key cancer driver mutations, potentially representing the earliest neoplastic precursor of IM-induced gastric cancer.\nConclusions: Overall, our IM organoid biobank captured the heterogeneous nature of IM, revealing mechanistic insights on IM pathogenesis and progression, offering an ideal platform for studying early gastric neoplastic transformation and chemoprevention.","abstract":"Background: Gastric intestinal metaplasia (IM) is a pre-cancerous stage spanning   a morphological spectrum that is poorly represented by human cell line models.\nObjective: We aim to establish and characterize human IM cell models to better understand IM progression along the cancer spectrum.\nDesign: A large human gastric IM organoid (IMO) cohort (n=28), their clonal derivatives and normal gastric organoids (n=42) for comparison were established. Comprehensive multi-omics profiling and functional characterization were performed.\nResults: Single-cell transcriptomes revealed IMO cells spanning a spectrum from hybrid gastric/intestinal to advanced intestinal differentiation. Their lineage trajectories connected different cycling and quiescent stem and progenitors, highlighting differences in gastric to IM transition and the potential origin of IM from STMN1 cycling isthmus stem cells. Hybrid IMOs showed impaired differentiation potential, high lineage plasticity beyond gastric or intestinal fates, and reactivation of a fetal gene program. \nCell populations in gastric IM and cancer tissues were highly similar to those derived from IMOs and exhibited a fetal signature. Genomically, IMOs showed elevated mutation burden, frequent chromosome 20 gain, and epigenetic de-regulation of many intestinal and gastric genes. Functionally, IMOs were FGF10 independent and showed downregulated FGFR2. Several IMOs exhibited a cell-matrix adhesion independent (CMi) subpopulation that displayed chromosome 20 gain but lacked key cancer driver mutations, potentially representing the earliest neoplastic precursor of IM-induced gastric cancer.\nConclusions: Overall, our IM organoid biobank captured the heterogeneous nature of IM, revealing mechanistic insights on IM pathogenesis and progression, offering an ideal platform for studying early gastric neoplastic transformation and chemoprevention.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-08-13T06:55:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007900","title":"Mutational Mechanisms in Multiply Relapsed Pediatric Acute Lymphoblastic Leukemia","description":"Pediatric acute lymphoblastic leukemia (ALL) is marked by low mutational load at initial diagnosis, which increases at relapse. To determine which processes are active in (relapsed) ALL and how they behave during disease progression before and after therapy, we performed whole genome sequencing on tumor samples of 29 multiply relapsed ALL patients. Mutational load increased upon relapse in 28 patients and every subsequent relapse in 22 patients, with UV-like damage, APOBEC activity, reactive oxygen species, thiopurine-associated damage and an unknown therapy component driving mutagenesis. Thiopurines were the most prominent source of new mutations in relapse, affecting over half of the studied patients and causing potential relapse-driving mutations in multiple patients. Mutational processes often affected patients over longer time periods, but could also occur in isolated events, suggesting the requirement of additional triggers. Our data pose mutational processes as prominent secondary drivers with an important role in ALL development and progression.","abstract":"Pediatric acute lymphoblastic leukemia (ALL) is marked by low mutational load at initial diagnosis, which increases at relapse. To determine which processes are active in (relapsed) ALL and how they behave during disease progression before and after therapy, we performed whole genome sequencing on tumor samples of 29 multiply relapsed ALL patients. Mutational load increased upon relapse in 28 patients and every subsequent relapse in 22 patients, with UV-like damage, APOBEC activity, reactive oxygen species, thiopurine-associated damage and an unknown therapy component driving mutagenesis. Thiopurines were the most prominent source of new mutations in relapse, affecting over half of the studied patients and causing potential relapse-driving mutations in multiple patients. Mutational processes often affected patients over longer time periods, but could also occur in isolated events, suggesting the requirement of additional triggers. Our data pose mutational processes as prominent secondary drivers with an important role in ALL development and progression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-08-13T09:28:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007901","title":"WENanoSeq__Investigating_the_clonal_dynamics_in_interstitial_lung_diseases_using_laser_captured_microdissection","description":"This study aims to characterise the mutational landscape and identify driver mutations in interstitial lung diseases (ILDs) including idiopathic pulmonary fibrosis, secondary pulmonary fibrosis overlapping with autoimmune conditions as well as stage IV sarcoidosis. Here, we will perform laser-captured microdissection and generate Whole exome NanoSeq data with fresh frozen bronchus and lung parenchymal tissues from patients with ILDs in order to better understand the mutational processes in these diseases.","abstract":"This study aims to characterise the mutational landscape and identify driver mutations in interstitial lung diseases (ILDs) including idiopathic pulmonary fibrosis, secondary pulmonary fibrosis overlapping with autoimmune conditions as well as stage IV sarcoidosis. Here, we will perform laser-captured microdissection and generate Whole exome NanoSeq data with fresh frozen bronchus and lung parenchymal tissues from patients with ILDs in order to better understand the mutational processes in these diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007902","title":"Rearrangements of viral and human genomes at human papillomavirus integration events and their allele-specific impacts on cancer genome regulation","description":null,"abstract":"The Oxford Nanopore long-read analysis of 72 cervical cancer genomes discovered genomic and epigenomic dysregulation originating at sites of human papillomavirus (HPV) integration. The integration events had allele-specific effects on the genome, methylome, and transcriptome, which sometimes resulted in the activation of cancer genes.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007903","title":"DERMATLAS__Malignant_mixed_tumour_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are: malignant mixed tumour.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are: malignant mixed tumour.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007904","title":"Tubulointerstitial fibrosis is the histological hallmark of chronic kidney disease (CKD). Hypoxia and inflammation (i.e., interleukin (IL)-1β signalling) are independent mediators of tubulointerstitial fibrosis. However, the physiological response of human kidney tubular cells to IL-1β/IL-1RI signalling under the hypoxic conditions of CKD is poorly understood and remains a clinical imperative for therapeutic targeting. This study reports that hypoxia and IL-1β act in synergy to trigger cell cycle arrest/cellular senescence of ex vivo patient-derived primary proximal tubular epithelial cells (PTECs).","description":"Hypoxia and interleukin (IL)-1β are independent mediators of tubulointerstitial fibrosis, the histological hallmark of chronic kidney disease (CKD). Here, we examine how hypoxia and IL-1β act in synergy to augment maladaptive proximal tubular epithelial cell (PTEC) repair in human CKD. Ex vivo patient-derived PTECs were cultured under normoxic (21% O2) or hypoxic (1% O2) conditions in the absence or presence of IL-1β and examined for maladaptive repair signatures. Hypoxic PTECs incubated with IL-1β displayed a discrete transcriptomic profile distinct from PTECs cultured under hypoxia alone, IL-1β alone or under normoxia. Hypoxia+IL-1β-treated PTECs had 692 ‘unique’ differentially expressed genes (DEGs) compared to normoxic PTECs, with ‘cell cycle’ the most significantly enriched KEGG pathway based on ‘unique’ down-regulated DEGs (including CCNA2, CCNB1 and CCNB2). Hypoxia+IL-1β-treated PTECs displayed signatures of cellular senescence, with reduced proliferation, G2/M cell cycle arrest, elevated senescence-associated β-galactosidase (SA-β-gal) activity and increased production of pro-inflammatory/fibrotic senescence-associated secretory phenotype (SASP) factors compared to normoxic conditions. Treatment of Hypoxia+IL-1β-treated PTECs with either a senolytic drug combination, quercetin+dasatinib, or a type I IL-1 receptor (IL-1RI) neutralizing antibody attenuated senescent cell burden. Our data identify a mechanism whereby hypoxia in combination with IL-1β/IL-1RI signalling trigger PTEC senescence, providing novel therapeutic and diagnostic check-points for restoring tubular regeneration in human CKD.","abstract":"Hypoxia and interleukin (IL)-1β are independent mediators of tubulointerstitial fibrosis, the histological hallmark of chronic kidney disease (CKD). Here, we examine how hypoxia and IL-1β act in synergy to augment maladaptive proximal tubular epithelial cell (PTEC) repair in human CKD. Ex vivo patient-derived PTECs were cultured under normoxic (21% O2) or hypoxic (1% O2) conditions in the absence or presence of IL-1β and examined for maladaptive repair signatures. Hypoxic PTECs incubated with IL-1β displayed a discrete transcriptomic profile distinct from PTECs cultured under hypoxia alone, IL-1β alone or under normoxia. Hypoxia+IL-1β-treated PTECs had 692 ‘unique’ differentially expressed genes (DEGs) compared to normoxic PTECs, with ‘cell cycle’ the most significantly enriched KEGG pathway based on ‘unique’ down-regulated DEGs (including CCNA2, CCNB1 and CCNB2). Hypoxia+IL-1β-treated PTECs displayed signatures of cellular senescence, with reduced proliferation, G2/M cell cycle arrest, elevated senescence-associated β-galactosidase (SA-β-gal) activity and increased production of pro-inflammatory/fibrotic senescence-associated secretory phenotype (SASP) factors compared to normoxic conditions. Treatment of Hypoxia+IL-1β-treated PTECs with either a senolytic drug combination, quercetin+dasatinib, or a type I IL-1 receptor (IL-1RI) neutralizing antibody attenuated senescent cell burden. Our data identify a mechanism whereby hypoxia in combination with IL-1β/IL-1RI signalling trigger PTEC senescence, providing novel therapeutic and diagnostic check-points for restoring tubular regeneration in human CKD.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-08-22T05:16:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007905","title":"HCA_Bone_Marrow_LEAP_project_RNA","description":"Using single-cell and spatial genomics methods to profile the in vivo and in vitro engineered bone marrow micro-environments","abstract":"During hematopoiesis, the bone marrow microenvironment triggers specific signalling in hematopoietic stem cells (HSCs), inducing their differentiation into multiple immune lineages. A main constraint in the field is the lack of human in vitro models to recapitulate this process and provide mechanistic insights into the early steps of immune cell differentiation. Here, we aim to generate the first artificial bone marrow microenvironment in a dish to mechanistically dissect how it shapes immune cell identity and function in humans. We will combine single-cell and spatial genomics methods to profile the in vivo and in vitro engineered models. This work has relevant translational opportunities for immunotherapy, regenerative medicine and the catalysation of chimeric antigen-immune cells (CAR-immune cells), opening up new avenues in hematopoiesis research.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007906","title":"Parkinson's Families Project","description":"SNP array data of 698 individuals with early onset and/or familial Parkinson's disease.","abstract":"SNP array data of 698 individuals with early onset and/or familial Parkinson's disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-08-23T13:48:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007907","title":"DERMATLAS__Apocrine_carcinoma_breast_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are apocrine carcinoma of the breast, to compare to their cutaneous counterpart.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are apocrine carcinoma of the breast, to compare to their cutaneous counterpart.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007908","title":"DERMATLAS__Apocrine_carcinoma_breast_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n        The cases in this cohort are apocrine carcinoma of the breast, to compare to their cutaneous counterpart.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are apocrine carcinoma of the breast, to compare to their cutaneous counterpart.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007909","title":"DERMATLAS__Syringoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Syringomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Syringomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007910","title":"DERMATLAS__Syringoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Syringomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Syringomas.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007911","title":"Organoid drug profiling identifies methotrexate as a therapy for SCCOHT, a rare pediatric cancer","description":"Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and lethal tumor in adolescent and young adult patients. Currently, there is no standard-of-care treatment for these patients. Reliable models that represent this disease and can be used for translational research are scarce. To model SCCOHTs, we have established eight patient-derived tumoroid lines from tumor lesions of three patients with SCCOHT. The tumoroids recapitulate genomic and transcriptomic characteristics of the corresponding patient tumors and capture intrapatient tumor heterogeneity. Organoid drug profiling using a library of 153 clinical compounds identified methotrexate as an effective and selective drug against SCCOHTs with a clinically relevant IC50 of 35 nmol/L. RNA sequencing demonstrated that methotrexate induced TP53 pathway activation and apoptosis. These data underscore that organoid technology can support the design of therapeutic strategies for rare cancers.","abstract":"Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and lethal tumor in adolescent and young adult patients. Currently, there is no standard-of-care treatment for these patients. Reliable models that represent this disease and can be used for translational research are scarce. To model SCCOHTs, we have established eight patient-derived tumoroid lines from tumor lesions of three patients with SCCOHT. The tumoroids recapitulate genomic and transcriptomic characteristics of the corresponding patient tumors and capture intrapatient tumor heterogeneity. Organoid drug profiling using a library of 153 clinical compounds identified methotrexate as an effective and selective drug against SCCOHTs with a clinically relevant IC50 of 35 nmol/L. RNA sequencing demonstrated that methotrexate induced TP53 pathway activation and apoptosis. These data underscore that organoid technology can support the design of therapeutic strategies for rare cancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-08-26T13:57:41+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007912","title":"Single cell whole genome sequencing of primary and metastatic samples with Direct Library Preparation (DLP+)","description":"Single cell whole genome sequencing of primary and metastatic samples with Direct Library Preparation (DLP+)","abstract":"Single cell whole genome sequencing of primary and metastatic samples with Direct Library Preparation (DLP+)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-08-27T14:28:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007913","title":"LCM_WGS__Thyroid_","description":"Whole genome sequencing through the low-input DNA pipeline in thyroid samples. Tissue will be processed either from laser capture microdissection or directly from bulk frozen/fixed/paraffin-embedded tissue. Insights will be gained here directly from the sequencing but also from using the data as a matched normal in Exome Nanoseq. Thyroid samples will be obtained from patients with and without thyroid disease.","abstract":"Investigating the driver landscape in thyroid, in both health and disease.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-08-28T14:39:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007914","title":"Test GWAS Data for Training and Computational Benchmarking","description":null,"abstract":"Background: Test GWAS Data for training and\n      computational benchmaring is often needed. This data set has\n      been generated from real Africa data to try to approximate LD,\n      population structure and site allele spectrum. The data has been\n      de-identified but as further protection of participants we\n      require participants to agree to conditions that they will not\n      attempt to re-identify samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-09-03T15:41:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007915","title":"Northern Ireland COhort for the Longitudinal study of Ageing","description":"The Northern Ireland COhort for the Longitudinal study of Ageing \n(NICOLA) is a representative sample of ~8,500 people from across \nNorthern Ireland. The study, which was set up in 2012, aims to \nunderstand what it is like to grow older in Northern Ireland.\n\n• NICOLA has a strong focus on molecular biomarkers \nso there is complementary genetic, epigenetic and \ntranscriptomic data available for a subset of individuals.\n• We inherit much of our DNA from our parents while a \nsmall amount of this material changes as we get older. \nIn NICOLA we have 551,839 directly genotyped and \n18,148,478 imputed Single Nucleotide Polymorphisms \n(SNPs) currently available for 2969 participants.\n• Summary statistics for the association of these gene \npolymorphisms with ~30 phenotypes were generated.\n• Epigenetics provides a link between our inherited DNA \nand environmental influences from a person’s diet, \nmedication and lifestyle. NICOLA has the epigenetic \nquality controlled profiles of 1984 individuals arising from \nvariations in DNA methylation at 862,927 genetic sites.","abstract":"The Northern Ireland COhort for the Longitudinal study of Ageing \n(NICOLA) is a representative sample of ~8,500 people from across \nNorthern Ireland. The study, which was set up in 2012, aims to \nunderstand what it is like to grow older in Northern Ireland.\n\n• NICOLA has a strong focus on molecular biomarkers \nso there is complementary genetic, epigenetic and \ntranscriptomic data available for a subset of individuals.\n• We inherit much of our DNA from our parents while a \nsmall amount of this material changes as we get older. \nIn NICOLA we have 551,839 directly genotyped and \n18,148,478 imputed Single Nucleotide Polymorphisms \n(SNPs) currently available for 2969 participants.\n• Summary statistics for the association of these gene \npolymorphisms with ~30 phenotypes were generated.\n• Epigenetics provides a link between our inherited DNA \nand environmental influences from a person’s diet, \nmedication and lifestyle. NICOLA has the epigenetic \nquality controlled profiles of 1984 individuals arising from \nvariations in DNA methylation at 862,927 genetic sites.","study_type":"Other","pubmed_ids":[36899371,37011634],"external_links":null,"is_released":true,"released_date":"2024-09-09T12:37:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007916","title":"Drug screening reveals new insight for chemoresistant hepatoblastoma","description":"Hepatoblastoma (HB) is the most prevalent form of pediatric liver cancer. Although the standard treatment, primarily based on cisplatin, is effective in 80% of patients, it falls short in high-risk cases due to the development of chemoresistance. \nTo identify new therapies overcoming this resistance, we screened 101 individual therapeutic compounds and 58 combinations, across 8 pediatric liver cancer cell lines. We identified ATR as a critical target to reverse cisplatin resistance. The ATR inhibitor elimusertib demonstrated the greatest synergy with cisplatin in 2D and 3D cultures and in subcutaneous xenograft models of cisplatin-resistant HB. This combination was found to enhance DNA damage and induces apoptosis through strong p53 activation.  \nIn conclusion, our study underscores the crucial role of ATR in cisplatin resistance and highlights the promising anti-proliferative effects of the Elimusertib/Cisplatin combination in cisplatin-resistant HB models, offering a potential new therapeutic option for treating high-risk and refractory HB.","abstract":"Hepatoblastoma (HB) is the most prevalent form of pediatric liver cancer. Although the standard treatment, primarily based on cisplatin, is effective in 80% of patients, it falls short in high-risk cases due to the development of chemoresistance. \nTo identify new therapies overcoming this resistance, we screened 101 individual therapeutic compounds and 58 combinations, across 8 pediatric liver cancer cell lines. We identified ATR as a critical target to reverse cisplatin resistance. The ATR inhibitor elimusertib demonstrated the greatest synergy with cisplatin in 2D and 3D cultures and in subcutaneous xenograft models of cisplatin-resistant HB. This combination was found to enhance DNA damage and induces apoptosis through strong p53 activation.  \nIn conclusion, our study underscores the crucial role of ATR in cisplatin resistance and highlights the promising anti-proliferative effects of the Elimusertib/Cisplatin combination in cisplatin-resistant HB models, offering a potential new therapeutic option for treating high-risk and refractory HB.","study_type":"Other","pubmed_ids":[41325782],"external_links":null,"is_released":true,"released_date":"2024-09-10T13:27:18+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007917","title":"Targeted_NanoSeq___Sorted_Blood","description":"Targeted NanoSeq to explore the driver landscape in sorted blood populations from donors in health and disease.","abstract":"Exploring the driver landscape in individual populations of cells from blood, across health, disease, and ageing","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007918","title":"Exome_NanoSeq___Ulcerative_Colitis","description":"Exome NanoSeq in colonic ulcerative colitis samples from a number of donors across different inflammation states.","abstract":"Investigating the driver landscape across a large number of colon specimens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007919","title":"Targeted_NanoSeq__Ulcerative_Colitis_","description":"Targeted NanoSeq in colonic ulcerative colitis samples from a number of donors across different inflammation states. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).","abstract":"Investigating the driver landscape across a large number of colon specimens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007920","title":"Spatial and temporal genomics of glioblastoma identifies phylogenetic trajectories of tumor evolution","description":null,"abstract":"Therapy resistance in glioblastoma remains an unmet clinical challenge. To more deeply understand tumor evolution, we generated genomic data from multi-regional and longitudinal samples that could power phylogenetic analyses. Together with long range mutation phasing, these data and a novel analytic framework captured evolutionary adaptations to local and systemic selective pressures. Phasing revealed that most mutations were acquired in cis, highlighting a previously unappreciated role for strand-specific mutagenesis in glioblastoma. Certain mutational signatures were associated with major clonal differentiation events, including SBS11 (temozolomide resistance), and SBS23, significantly enriched in recurrences. DNA mismatch repair deficiency signatures SBS6 and SBS15 arose independently of each other and differentially affected ECM and cytoskeleton-related pathways. Intriguingly, SBS15 had a significant association with improved survival, while SBS6 was significantly associated with non-hotspot POLD1 and POLE mutations. These novel findings extend our current understanding of the etiology and impact of mutagenic processes during glioblastoma evolution.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007921","title":"Stratton__WGS___Identification_of_Early_Life_Exposures_in_Paediatric_Colonic_Crypts_of_Healthy_Individuals","description":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. Whole genome sequencing of colon crypts from healthy paediatric individuals for identification of early life exposure to carcinogens.\n","abstract":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. Whole genome sequencing of colon crypts from healthy paediatric individuals for identification of early life exposure to carcinogens.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-09-16T11:01:34+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007922","title":"Clonal_dynamics_and_the_mutational_landscape_in_PTEN_hamartoma_tumour_syndrome___WGS","description":"This work aims to study the somatic impact, in normal and malignant tissues, of varying germline cancer predisposition syndromes.","abstract":"A multitude pathogenic germline variants are known to cause a broad spectrum of cancer predispostion. The underlying mechanism that leads to variable penetrance and expressivity associated with these variants, in a tissue specific manner, is poorly understood. Using serially sampled specimens from individuals with different underlying germline predisposition to cancer, we aim to elucidate the underlying somatic mutational landscape and clonal dynamics that explain the wide spectrum of clinical phenotype.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007923","title":"Clonal_dynamics_and_the_mutational_landscape_in_PTEN_hamartoma_tumour_syndrome___DupSeq","description":"This work aims to study the somatic impact, in normal and malignant tissues, of varying germline cancer predisposition syndromes.","abstract":"A multitude pathogenic germline variants are known to cause a broad spectrum of cancer predispostion. The underlying mechanism that leads to variable penetrance and expressivity associated with these variants, in a tissue specific manner, is poorly understood. Using serially sampled specimens from individuals with different underlying germline predisposition to cancer, we aim to elucidate the underlying somatic mutational landscape and clonal dynamics that explain the wide spectrum of clinical phenotype.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007924","title":"Clonal_dynamics_and_the_mutational_landscape_in_PTEN_hamartoma_tumour_syndrome___Targeted_NanoSeq","description":"This work aims to study the somatic impact, in normal and malignant tissues, of varying germline cancer predisposition syndromes.","abstract":"A multitude pathogenic germline variants are known to cause a broad spectrum of cancer predispostion. The underlying mechanism that leads to variable penetrance and expressivity associated with these variants, in a tissue specific manner, is poorly understood. Using serially sampled specimens from individuals with different underlying germline predisposition to cancer, we aim to elucidate the underlying somatic mutational landscape and clonal dynamics that explain the wide spectrum of clinical phenotype.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007925","title":"Study cancers in a cohort of cancer and noncancer patients.","description":"Study cancers in a cohort of cancer and noncancer patients.","abstract":"Study cancers in a cohort of cancer and noncancer patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007926","title":"Clonal Driver Neoantigen Loss under EGFR TKI and Immune Selection Pressures","description":"NNN","abstract":"NNN","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-09-20T08:42:08+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007927","title":"Whole_Genome_Sequencing_OMELib__Cord_NSX_","description":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the CBSB.","abstract":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the CBSB.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007928","title":"RNA_Seq_OMELib__Cord_Blood___NSX_","description":"The transcriptional landscape of haematopoietic cells will be characterized by RNA Seq following amplification of RNA/cDNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the CBSB.","abstract":"The transcriptional landscape of haematopoietic cells will be characterized by RNA Seq following amplification of RNA/cDNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the CBSB.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007929","title":"WGS_Determining_the_mutation_burden_in_non_invasive_lung_samples","description":"The aim of this study is to investigate the mutational landscape in non-invasive samples from human upper airway. This project is for generating the standard WGS dataset as germline controls from the whole blood samples.","abstract":"The aim of this study is to investigate the mutational landscape in non-invasive samples from human upper airway. This project is for generating the standard WGS dataset as germline controls from the whole blood samples.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007930","title":"Mapping the human hematopoietic stem and progenitor cell hierarchy through integrated single-cell proteomics and transcriptomics","description":"Single-cell transcriptomics (scRNA-seq) has enabled the characterization of cell state heterogeneity and recapitulation of differentiation trajectories. However, since proteins are the main functional entities in cells, the exclusive use of mRNA measurements comes at the risk of missing important biological information. Here we leverage recent technological advances in single-cell proteomics by Mass Spectrometry (scp-MS) to generate the first scp-MS dataset of an in vivo differentiation hierarchy encompassing over 2,500 human CD34+ hematopoietic stem and progenitor cells. Through integration with scRNA-seq, we identify proteins that are important for stem cell quiescence, which were not indicated by their mRNA transcripts, and demonstrate functional expression covariance during differentiation that is only detectable on protein level. Finally, we show that modeling translation dynamics can infer cell progression during differentiation and explain 45% more protein variation from mRNA than linear correlation. Our work serves as a framework for future single-cell multi-omics studies across biological systems.","abstract":"Single-cell transcriptomics (scRNA-seq) has enabled the characterization of cell state heterogeneity and recapitulation of differentiation trajectories. However, since proteins are the main functional entities in cells, the exclusive use of mRNA measurements comes at the risk of missing important biological information. Here we leverage recent technological advances in single-cell proteomics by Mass Spectrometry (scp-MS) to generate the first scp-MS dataset of an in vivo differentiation hierarchy encompassing over 2,500 human CD34+ hematopoietic stem and progenitor cells. Through integration with scRNA-seq, we identify proteins that are important for stem cell quiescence, which were not indicated by their mRNA transcripts, and demonstrate functional expression covariance during differentiation that is only detectable on protein level. Finally, we show that modeling translation dynamics can infer cell progression during differentiation and explain 45% more protein variation from mRNA than linear correlation. Our work serves as a framework for future single-cell multi-omics studies across biological systems.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-09-20T11:45:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007931","title":"Stratton__WGS_NovaseqX_non_malignant_colon_and_colorectal_cancer","description":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. This study will explore the incidence of early onset colorectal cancer (eoCRC) has been increasing over the last few decades. Results from the whole genome sequencing of 982 colorectal cancers in the Mutographs study have identified several mutational signatures associated with the microbiome, including the COSMIC reference signature SBS88. This signature is caused by exposure to Colibactin, a toxin produced by strains of Escherichia Coli which carry the pks pathogenicity island. The mutation burden of SBS88 was positively correlated with the age standardised rate (ASR) of CRC and was significantly more frequent in eoCRC. In addition, previous studies of the normal colon have shown that colibactin exposure likely occurs within the first decade of life. These results together suggest that the microbiome is contributing to the increase in eoCRC, and that it might be possible to assess the risk of eoCRC and/or control eoCRC incidence by monitoring the gut microbiome. This study aims to sequence both colorectal cancer and non-malignant colon to establish whether there is a causal relationship between colibactin exposure and eoCRC. ","abstract":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. This study will explore the incidence of early onset colorectal cancer (eoCRC) has been increasing over the last few decades. Results from the whole genome sequencing of 982 colorectal cancers in the Mutographs study have identified several mutational signatures associated with the microbiome, including the COSMIC reference signature SBS88. This signature is caused by exposure to Colibactin, a toxin produced by strains of Escherichia Coli which carry the pks pathogenicity island. The mutation burden of SBS88 was positively correlated with the age standardised rate (ASR) of CRC and was significantly more frequent in eoCRC. In addition, previous studies of the normal colon have shown that colibactin exposure likely occurs within the first decade of life. These results together suggest that the microbiome is contributing to the increase in eoCRC, and that it might be possible to assess the risk of eoCRC and/or control eoCRC incidence by monitoring the gut microbiome. This study aims to sequence both colorectal cancer and non-malignant colon to establish whether there is a causal relationship between colibactin exposure and eoCRC. ","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007932","title":"Analysis_of_T_Cell_Activation_and_Treg_Suppression","description":"Isolated regulatory T cells from healthy donors are expanded and subjected to gene-editing using CRISPR/Cas9 to delete genes associated with immune diseases. Changes in expression of the expanding Tregs are measured at multiple timepoints by RNA sequencing. These edited Tregs (eTregs) are then placed in a co-culture of naïve T cells and macrophages. We performed scRNA sequencing to assess regulation of T cell activation. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"T-cell activation is tightly regulated by delivery of stimulatory signals through antigen-presenting cells and suppressive capacity exerted by regulatory T cells. Here, we have isolated Tregs from blood of healthy donors which were then activated using anti-CD3 anti-CD28. RNA-sequencing was performed to identify changes in gene-expression at three timepoints in order to identify changes in gene-expression caused by the expansion process. The expanded Tregs are then subjected to CRISPR/Cas9-editing and then co-cultured along with isolated naïve T-cells and polarised macrophages from the same healthy donor in the presence of anti-CD3 to identify genes linked to Treg suppressive capability. Single-cell gene expression was then performed on co-cultures containing CRISPR-Cas9-edited Tregs from 3 healthy donors in order to identify the genetic background of T-cell activation and Treg suppression.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007933","title":"HG_TP10476_JAGUAR_","description":"The aim of Project JAGUAR is to characterise immune cell population from Latin American populations and to characterise regulatory networks and mechanisms influenced by genetic variation.","abstract":"The aim of Project JAGUAR is to characterise immune cell population from Latin American populations and to characterise regulatory networks and mechanisms influenced by genetic variation. Blood Samples will be collected from a total of 1,080 participants from 7 Latin American countries -Mexico, Chile, Brazil, Peru, Uruguay, Colombia and Argentina. PBMCs will be isolated at sites, aliquoted into a minimum of 3 tubes, frozen and shipped to Sanger. Whole blood sample will be aliquoted at sites and shipped to Sanger for DNA extraction and whole genome sequencing. Transcriptome, proteome and chromatin accessibility profiling will be combined to build a high resolution multimodal cell atlas of T cells, monocytes, B cells, NKs and dendritic cells subpopulations from these samples. We aim to achieve the following:\n\n1. To deeply characterize the immune cell composition across the LATAM populations.\n2. To characterise regulatory networks and mechanisms influenced by genetic variation across LATAM populations\n3. To build at LATAM PBMC biobank for future studies such as those linking genetic variants to changes in gene expression.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007934","title":"Multi-Layered Molecular Profiling Informs the Diagnosis and Targeted Therapy of Desmoplastic Small Round Cell Tumor","description":"Desmoplastic small  round cell tumor (DSRCT) is an ultra-rare soft tissue sarcoma with dismal prognosis and limited therapeutic options. \nHere, we identified individual therapeutic targets in a cohort of 30 DSRCT patients by  use of multilayered molecular profiling (genomic, transcriptomic, and (phospho-)proteomic analyses) within the DKFZ NCT DKTK MASTER program.\n28 of the 30 patients received at least one personalized treatment recommendation. In line with the observation that DSRCTs are an entity with a low mutational load, most of the treatment recommendations were based on target gene or -protein expression. 13 patients received a recommended therapy, resulting in  four partial responses, four stable diseases, and five progressive diseases. Eight of 13 patients received the multi tyrosine kinase inhibitor pazopanib, with mixed response. Based on high ERBB2 expression levels, two patients received the antibody drug conjugate trastuzumab deruxtecan (T-DXd), showed exceptional, long-lasting responses and are currently (8/2024) still on treatment and progression-free. We detected high ERBB2 protein expression in all DSRCT samples with proteome data (n = 9), which suggests that ERBB2 may be a particularly useful therapeutic target for DSRCT patients. For one of the two exceptional responders we did not detect a substantial ERBB2/HER2 overexpression, which may indicate that T-DXd could also be efficacious in DSRCT patients with low levels of HER2, as also described for breast cancer patients.\nIn conclusion, multi-omic molecular profiling revealed personalized therapeutic targets in patients with DSRCT with HER2 targeting, with T-DXd as a promising therapeutic option for this ultra-rare and difficult-to-treat tumor entity.","abstract":"Desmoplastic small  round cell tumor (DSRCT) is an ultra-rare soft tissue sarcoma with dismal prognosis and limited therapeutic options. \nHere, we identified individual therapeutic targets in a cohort of 30 DSRCT patients by  use of multilayered molecular profiling (genomic, transcriptomic, and (phospho-)proteomic analyses) within the DKFZ NCT DKTK MASTER program.\n28 of the 30 patients received at least one personalized treatment recommendation. In line with the observation that DSRCTs are an entity with a low mutational load, most of the treatment recommendations were based on target gene or -protein expression. 13 patients received a recommended therapy, resulting in  four partial responses, four stable diseases, and five progressive diseases. Eight of 13 patients received the multi tyrosine kinase inhibitor pazopanib, with mixed response. Based on high ERBB2 expression levels, two patients received the antibody drug conjugate trastuzumab deruxtecan (T-DXd), showed exceptional, long-lasting responses and are currently (8/2024) still on treatment and progression-free. We detected high ERBB2 protein expression in all DSRCT samples with proteome data (n = 9), which suggests that ERBB2 may be a particularly useful therapeutic target for DSRCT patients. For one of the two exceptional responders we did not detect a substantial ERBB2/HER2 overexpression, which may indicate that T-DXd could also be efficacious in DSRCT patients with low levels of HER2, as also described for breast cancer patients.\nIn conclusion, multi-omic molecular profiling revealed personalized therapeutic targets in patients with DSRCT with HER2 targeting, with T-DXd as a promising therapeutic option for this ultra-rare and difficult-to-treat tumor entity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-09-26T09:22:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007935","title":"HCA_Gut_Teichmann_MM_RNA_Managed_Access","description":"This study aims to profile gut tissue of infants, primarily those born preterm (defined as babies born alive before 37 weeks of pregnancy are completed). To that end, we will generate single cell RNA-seq data of leftover intestinal tissue collected during resection surgeries, which will enable a better understanding of early life gut development.","abstract":"The gastrointestinal (GI) tract performs diverse roles related to digestion, barrier function, immune regulation, and the absorption of nutrients. As a result, understanding its development and maturation is important for ensuring proper health and growth throughout the lifespan. While we have previously generated data characterizing fetal, pediatric, and adult intestinal development, we aim to further expand this dataset with samples from preterm and neonatal gut. This data will be critical in evaluating the possibility of multiple developmental conditions in preterm infants, including necrotizing enterocolitis.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007936","title":"HCA_Immune_PBMC_Teichmann_LK_RNA_managed_acces","description":"The aim of this study is to characterise CD8 T cell populations that are specific to prevalent viruses in the healthy blood donors. We obtained PBMC samples from a commercial supplier that have been HLA-typed and pre-tested for reactivity against EBV, CMV, and influenza using ELISPOT and peptide pool stimulation.","abstract":" In this study, we are investigating cellular heterogeneity in transcriptomic signatures and T cell receptor (TCR) repertoire overlap for n=15 PBMC samples, which are analysed with the 10x Genomics BEAM-T protocol followed by single cell-sequencing.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-09-26T15:29:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007937","title":"Novel paediatric case of a spinal high-grade astrocytoma with piloid features in a patient with Noonan Syndrome","description":"Noonan Syndrome (NS) is associated with an increased risk of low-grade central nervous system tumours in children but only very rarely associated with high-grade gliomas. Here we describe the first reported case of a spinal high-grade astrocytoma with piloid features (HGAP) in a child with NS. This case was a diagnostic and treatment dilemma, prior to whole-genome germline and tumour sequencing, tumour transcriptome sequencing and DNA methylation analysis. The methylation profile matched strongly with HGAP and sequencing identified somatic FGFR1 and NF1 variants and a PTPN11 germline pathogenic variant. Therapeutic targets were identified but also alterations novel to HGAP such as differential expression of VEGFA and PD-L1. The germline PTPN11 finding has not been previously described in individuals with HGAP.  This case underscores the power of precision medicine from a diagnostic, therapeutic and clinical management perspective, and describes an association between HGAP and NS which has not previously been reported.","abstract":"Noonan Syndrome (NS) is associated with an increased risk of low-grade central nervous system tumours in children but only very rarely associated with high-grade gliomas. Here we describe the first reported case of a spinal high-grade astrocytoma with piloid features (HGAP) in a child with NS. This case was a diagnostic and treatment dilemma, prior to whole-genome germline and tumour sequencing, tumour transcriptome sequencing and DNA methylation analysis. The methylation profile matched strongly with HGAP and sequencing identified somatic FGFR1 and NF1 variants and a PTPN11 germline pathogenic variant. Therapeutic targets were identified but also alterations novel to HGAP such as differential expression of VEGFA and PD-L1. The germline PTPN11 finding has not been previously described in individuals with HGAP.  This case underscores the power of precision medicine from a diagnostic, therapeutic and clinical management perspective, and describes an association between HGAP and NS which has not previously been reported.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-09-26T23:30:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007938","title":"UTSW_steatotic_liver_disease","description":"Whole Exome and Targeted NanoSeq of steatotic liver disease (ArLD/MASLD) from donors as part of UTSW/WTSI collaboration.","abstract":"Part of the development of the chronic liver disease somatic mutational atlas - studying the adaptive mutational pathways developed by hepatocytes on their path towards end-stage liver disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007939","title":"UTSW_rare_liver_path","description":"Whole Exome and Targeted NanoSeq of rare chronic liver disease pathologies from donors as part of UTSW/WTSI collaboration.","abstract":"Part of the development of the chronic liver disease somatic mutational atlas - studying the adaptive mutational pathways developed by hepatocytes on their path towards end-stage liver disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007940","title":"AIH_lymphocytes_exome","description":"Whole exome and targeted nanoseq of laser capture microdissected lymphocyte clusters in autoimmune hepatitis.","abstract":"Part of the development of the chronic liver disease somatic mutational atlas - studying the adaptive mutational pathways developed by hepatocytes on their path towards end-stage liver disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007941","title":"Ewing and Ewing-like-sarcoma tumoroid biobank reveals distinct drug sensitivities: translocation makes the difference","description":"Ewing sarcoma (ES) and Ewing-like sarcomas (ELS) are highly aggressive tumors found in soft tissues and bone of mostly children and young adults. Despite being different in many aspects, including genetics, possible cell-of-origin, and pathology, patients with any of these entities all receive the same therapeutic regimen. Currently, there is a lack of preclinical cell models that can predict drug response of these entities in vitro. Here, we describe a pediatric ES and ELS tumor organoid (tumoroid) biobank containing tumoroids with different translocations, including EWSR1::FLI1, EWSR1::ERG, CIC::DUX4, and BCOR-rearrangements. Using histology, whole genome sequencing and RNA sequencing, we demonstrate that these tumoroids retain key properties of their matching patient tumors. In addition, we traced tumor subclones in the tumoroids across patient-matched longitudinal samples, which showed that cellular heterogeneity was maintained. We subsequently performed drug screening on the tumoroid models, which unveiled entity-specific drug sensitivity to various cytotoxic compounds and targeted compounds, including MCL-1 inhibitors for CIC::DUX4 sarcomas. Taken together, this newly established ES and ELS patient-derived tumoroid biobank generates a unique source of material for future basic cancer research and drug-screening.","abstract":"Ewing sarcoma (ES) and Ewing-like sarcomas (ELS) are highly aggressive tumors found in soft tissues and bone of mostly children and young adults. Despite being different in many aspects, including genetics, possible cell-of-origin, and pathology, patients with any of these entities all receive the same therapeutic regimen. Currently, there is a lack of preclinical cell models that can predict drug response of these entities in vitro. Here, we describe a pediatric ES and ELS tumor organoid (tumoroid) biobank containing tumoroids with different translocations, including EWSR1::FLI1, EWSR1::ERG, CIC::DUX4, and BCOR-rearrangements. Using histology, whole genome sequencing and RNA sequencing, we demonstrate that these tumoroids retain key properties of their matching patient tumors. In addition, we traced tumor subclones in the tumoroids across patient-matched longitudinal samples, which showed that cellular heterogeneity was maintained. We subsequently performed drug screening on the tumoroid models, which unveiled entity-specific drug sensitivity to various cytotoxic compounds and targeted compounds, including MCL-1 inhibitors for CIC::DUX4 sarcomas. Taken together, this newly established ES and ELS patient-derived tumoroid biobank generates a unique source of material for future basic cancer research and drug-screening.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-10-02T11:03:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007942","title":"WENanoSeq___Investigating_the_Role_of_Somatic_Mutations_in_Inflammatory_Liver_Disease","description":"This is an exploratory study aimed at investigating the mutational landscape in inflammatory liver diseases and assessing its relevance to the initiation and progression of these diseases.\nWe aim to \n1.\tIdentify genetic alterations in inflammatory liver diseases.\n2.\tDetermine which cell populations harbour with genetic alterations.\n3.\tCharacterise the functional role of the genetic alterations.","abstract":"Inflammatory liver diseases are mediated by acute or chronic tissue inflammation in the liver which can lead to fibrosis and cirrhosis. There can be several causes of liver inflammation including autoimmunity, chemical exposure and viruses. Autoimmune liver disease such as autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are debilitating conditions where the immune system attacks different parts of the liver. The cause of these conditions is unknown, and most treatments are ineffective with liver transplantation often being required as the disease progresses.\n\nGenetic and environmental factors contribute to the variability in the disease course and response to treatment among different individuals. It is not clear if the mutations found in the different tissues of the liver can play a part in the development and progression of these diseases. \n\nThis study aims to use novel methods to identify mutations that drive progression or protect the cells from inflammatory damage to identify in the different types of tissues of individuals with inflammatory liver diseases.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007943","title":"LCMB___Investigating_the_Role_of_Somatic_Mutations_in_Inflammatory_Liver_Disease","description":"This is an exploratory study aimed at investigating the mutational landscape in inflammatory liver diseases and assessing its relevance to the initiation and progression of these diseases.\nWe aim to \n1.\tIdentify genetic alterations in inflammatory liver diseases.\n2.\tDetermine which cell populations harbour with genetic alterations.\n3.\tCharacterise the functional role of the genetic alterations.","abstract":"Inflammatory liver diseases are mediated by acute or chronic tissue inflammation in the liver which can lead to fibrosis and cirrhosis. There can be several causes of liver inflammation including autoimmunity, chemical exposure and viruses. Autoimmune liver disease such as autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are debilitating conditions where the immune system attacks different parts of the liver. The cause of these conditions is unknown, and most treatments are ineffective with liver transplantation often being required as the disease progresses.\n\nGenetic and environmental factors contribute to the variability in the disease course and response to treatment among different individuals. It is not clear if the mutations found in the different tissues of the liver can play a part in the development and progression of these diseases. \n\nThis study aims to use novel methods to identify mutations that drive progression or protect the cells from inflammatory damage to identify in the different types of tissues of individuals with inflammatory liver diseases.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007944","title":"Methylation Array and WGS Data for 'Oligodendrogliomas originate in early childhood, accelerate growth through clonal evolution and have predictable recurrence times'","description":"Oligodendrogliomas are slowly growing central-nervous-system tumors that inevitably progress. Here, we elucidate how genetic evolution shapes growth and recurrence of these tumors by combining deep whole-genome sequencing of primary-relapse pairs with molecular clock analysis and mathematical inference. We find that oligodendrogliomas originate in childhood and evolve over decades with increasing growth rate. Growth acceleration is linked to subclonal selection, with TERT promoter mutations having strong impact. Weaker selection was associated with mutations in CIC, NOTCH1, ZBTB20 or ATM, or was not associated with known drivers. Relapse tumors showed ongoing subclonal selection, with or without known drivers. The time to recurrence of individual resected oligodendrogliomas was determined jointly by the growth rate of the primary tumor and the extent of surgical resection. Thus, our findings indicate that the dynamics of tumor evolution and recurrence can be predicted, on a personalized basis, using genome sequencing of the primary tumor.","abstract":"Oligodendrogliomas are slowly growing central-nervous-system tumors that inevitably progress. Here, we elucidate how genetic evolution shapes growth and recurrence of these tumors by combining deep whole-genome sequencing of primary-relapse pairs with molecular clock analysis and mathematical inference. We find that oligodendrogliomas originate in childhood and evolve over decades with increasing growth rate. Growth acceleration is linked to subclonal selection, with TERT promoter mutations having strong impact. Weaker selection was associated with mutations in CIC, NOTCH1, ZBTB20 or ATM, or was not associated with known drivers. Relapse tumors showed ongoing subclonal selection, with or without known drivers. The time to recurrence of individual resected oligodendrogliomas was determined jointly by the growth rate of the primary tumor and the extent of surgical resection. Thus, our findings indicate that the dynamics of tumor evolution and recurrence can be predicted, on a personalized basis, using genome sequencing of the primary tumor.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007945","title":"Multi-omics analysis of cocaine use disorder in postmortem brain tissue of the ventral striatum [Proteomics data to study EGAS50000000623]","description":"We performed a multi-omics analysis of cocaine use disorder in postmortem human brain tissue of the ventral striatum in N=41 individuals (N=20 CUD cases, N=21 non-affected individuals). From the postmortem brain tissue samples, we generated miRNA-seq, RNA-seq, proteomics, and snRNA-seq data. The miRNA-seq, RNA-seq and snRNA-seq datasets can be found in the EGA under study ID EGAS50000000623. Proteomics data is deposited under study ID EGAS00001007945 (this study). \nThe proteomic dataset was obtained using TMT-labeling. Measurement was performed on an Orbitrap Fusion Lumos device.","abstract":"We performed a multi-omics analysis of cocaine use disorder in postmortem human brain tissue of the ventral striatum in N=41 individuals (N=20 CUD cases, N=21 non-affected individuals). From the postmortem brain tissue samples, we generated miRNA-seq, RNA-seq, proteomics, and snRNA-seq data. The miRNA-seq, RNA-seq and snRNA-seq datasets can be found in the EGA under study ID EGAS50000000623. Proteomics data is deposited under study ID EGAS00001007945 (this study). \nThe proteomic dataset was obtained using TMT-labeling. Measurement was performed on an Orbitrap Fusion Lumos device.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-10-10T13:02:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007946","title":"PTA_thyroid__RNA_","description":"Exploring the somatic mutations in single cells derived from the thyroid","abstract":"Exploring the somatic mutations in single cells derived from the thyroid","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-10-11T09:29:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007947","title":"PTA_PBMCs__DNA_","description":"Exploring the somatic mutations in single cells derived from the blood.","abstract":"Exploring the somatic mutations in single cells derived from the blood.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007948","title":"PTA_PBMCs__RNA_","description":"Exploring the somatic mutations in single cells derived from the blood.","abstract":"Exploring the somatic mutations in single cells derived from the blood.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007949","title":"Targeted_NanoSeq__parathyroids_","description":"Exploring somatic mutations in parathyroid glands in health and disease","abstract":"Exploring somatic mutations in parathyroid glands in health and disease","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007950","title":"Exome_NanoSeq__parathyroids_","description":"Exploring somatic mutations in parathyroid glands in health and disease","abstract":"Exploring somatic mutations in parathyroid glands in health and disease","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007951","title":"LCM_WES__parathyroids_","description":"Exploring somatic mutations in parathyroid glands in health and disease","abstract":"Exploring somatic mutations in parathyroid glands in health and disease","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007952","title":"HCA_Heart_Cardiomyocytes_Teichmann_JP_RNA","description":"Cardiomyocytes differentiated from human pluripotent stem cells will be perturbed e.g. by transcription factor overexpression or addition of cytokines/metabolites, and harvested for single cell sequencing. This will enable the comparison of phenotype and gene regulation between perturbed and baseline states, guiding understanding of cardiomyocyte phenotype regulation","abstract":"Recent single-cell atlases of the human developing and adult heart have provided unprecedented resolution of cardiac cells. Cardiomyocytes, a major cell type of the heart, have been extensively profiled to reveal a spectrum of phenotypes, from contractile to conductive. However, in vitro models of cardiomyocytes retain foetal characteristics and lack the phenotypic diversity, maturity and specificity observed in vivo. This project employs a perturbation approach i.e. altering transcription factor expression or targeting cells with a metabolite/cytokine, to measure the differences in gene regulation in in vitro-derived cardiomyocytes under perturbed conditions and thus guide understanding of the regulatory principles of cardiomyocyte phenotypes, with the ultimate goal of guiding the precision engineering of cardiomyocytes subtypes in vitro. ","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007953","title":"Spatial whole-genome sequencing study in gallbladder adenocarcinoma","description":"Intratumoral heterogeneity and Darwinian selection are the core mechanism of cancer progression. Here, we illustrate the comprehensive landscapes of genomic heterogeneity and evolution of cancer subclones at the microscopic level using whole-genome sequences from 29 micropatches obtained from gallbladder adenocarcinoma.","abstract":"Intratumoral heterogeneity and Darwinian selection are the core mechanism of cancer progression. Here, we illustrate the comprehensive landscapes of genomic heterogeneity and evolution of cancer subclones at the microscopic level using whole-genome sequences from 29 micropatches obtained from gallbladder adenocarcinoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007954","title":"Single-cell RNA-sequencing of CSF cells and PBMCs from individuals with neurological disorders","description":"We undertook single-cell RNA sequencing to establish gene expression and lymphocyte receptor sequences of  CSF and peripheral blood leukocytes derived from patients with a variety of inflammatory, infectious and non-inflammatory neurological disorders. The aim of the study was the investigation of functional changes of the cells involved in neuroinflammatory responses.","abstract":"We undertook single-cell RNA sequencing to establish gene expression and lymphocyte receptor sequences of  CSF and peripheral blood leukocytes derived from patients with a variety of inflammatory, infectious and non-inflammatory neurological disorders. The aim of the study was the investigation of functional changes of the cells involved in neuroinflammatory responses.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-10-16T15:07:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007955","title":"PhIP-seq of Japanese patients with SLE","description":"Bacteriophage Immunoprecipitation Sequencing (PhIP-Seq) datasets of three eHHV-6B-positive SLE patients (three technical replicates), six eHHV-6B-negative SLE patients (three technical replicates), and a negative control lacking sera or plasma (12 technical replicates; Illumina NextSeq) and sequencing data of HHV-6 peptide phage library (two technical replicates; Illumina NextSeq).","abstract":"Bacteriophage Immunoprecipitation Sequencing (PhIP-Seq) datasets of three eHHV-6B-positive SLE patients (three technical replicates), six eHHV-6B-negative SLE patients (three technical replicates), and a negative control lacking sera or plasma (12 technical replicates; Illumina NextSeq) and sequencing data of HHV-6 peptide phage library (two technical replicates; Illumina NextSeq).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-10-18T06:06:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007956","title":"Single_cell_HSC_colony_WGS_gene_therapy_trials___Phase2","description":"This study looks at patients undergoing gene therapy for genetic blood  and immune disorders, in particular sickle cell disease. From each patient, single blood HSPC colonies are grown from patient blood at multiple time points: pre gene transduction, post-transduction,  and post-infusion (at several time points).  Whole-genome sequencing will be performed on DNA from these colonies and somatically-acquired mutations will be called. Using these mutations, a phylogeny of these cells can be inferred and further inferences can be made about the gene therapy transduction and engraftment steps.","abstract":"Sickle cell disease (SCD) is an inherited disorder causing considerable morbidity and mortality due to polymerisation of sickle haemoglobin causing deformation of red cells and vaso-occlusion in multiple organs. It is associated with an increased risk of leukemia. Understanding the reasons behind this is particularly important as we move into an era where transplantation and cellular therapies are becoming increasingly utilized. We will be assessing mutational signatures and burdens in normal blood cells, as well as the burden of expanded clones harbouring driver mutations in patients with SCD. We will be comparing these to an age and ethnically matched control cohort (where possible) to better understand how SCD impacts the mutation landscape and clonal dynamics of the haematopoietic system.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007957","title":"Integrated genomic analysis for HCC","description":"Liver cancer is a common malignancy and is the third cause of cancer-related death in the world and hepatocellular carcinoma (HCC) is the major type of liver cancer, accounting for ~90% of cases. Only 20 ~ 30% of patients can benefit from combined immunotherapy and targeted therapy due to the high inter-tumor heterogeneity of HCC. This work aims to identify homogeneous and robust molecular subtypes in HCC based on a large, homogenous and well-annotated cohort. We performed whole genome/exome sequencing (WGS/WES) and/or RNA sequencing (RNA-seq) on 529 HCC from 461 patients collected mainly in France. Based on the great consistence between genomic and transcriptomic data, we identified 9 robust HCC subtypes mainly based on driver mutations. And we further characterized HCC subtypes using genomic, transcriptomic and clinicopathological features. Among 9 subtypes, 5 subtypes belonged to chromosome instable tumors, while 3 subtypes belonged to chromosome stable tumors. In addition, our subtypes were associated with prognosis and we also found different distributions of subtypes across various features, such as etiology and gender. Our study provided a robust molecular classification based on a large HCC dataset from Western country, it improves our understanding of the mechanisms of carcinogenesis and will facilitate development of genome-based precision medicine in HCC.","abstract":"Liver cancer is a common malignancy and is the third cause of cancer-related death in the world and hepatocellular carcinoma (HCC) is the major type of liver cancer, accounting for ~90% of cases. Only 20 ~ 30% of patients can benefit from combined immunotherapy and targeted therapy due to the high inter-tumor heterogeneity of HCC. This work aims to identify homogeneous and robust molecular subtypes in HCC based on a large, homogenous and well-annotated cohort. We performed whole genome/exome sequencing (WGS/WES) and/or RNA sequencing (RNA-seq) on 529 HCC from 461 patients collected mainly in France. Based on the great consistence between genomic and transcriptomic data, we identified 9 robust HCC subtypes mainly based on driver mutations. And we further characterized HCC subtypes using genomic, transcriptomic and clinicopathological features. Among 9 subtypes, 5 subtypes belonged to chromosome instable tumors, while 3 subtypes belonged to chromosome stable tumors. In addition, our subtypes were associated with prognosis and we also found different distributions of subtypes across various features, such as etiology and gender. Our study provided a robust molecular classification based on a large HCC dataset from Western country, it improves our understanding of the mechanisms of carcinogenesis and will facilitate development of genome-based precision medicine in HCC.","study_type":"Other","pubmed_ids":[42156413],"external_links":null,"is_released":true,"released_date":"2024-10-18T10:52:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007958","title":"PROFILE_Metagenomics","description":"Crohn's disease is a chronic, relapsing form of inflammatory bowel disease (IBD) characterised by recurrent flares that can lead to progressive bowel damage. Convential drug therapies for IBD patients involve steroids treatment and advance biological immunomodulators to keep patients into remission. For newly diagnosed patients, disease progression and response to treatment is higly unpredictable however diverse studies suggest that earlier therapeutical intervention results in better clinical outcome and mitigates the need of surgical resection. There is a need for the identification of robust biomarkers that can predict treatment response to range of biologics used for treatment in IBD pathology. \nLimited data from small and heterogeneous IBD patient population indicates an association between treatment outcome and diverse gut microbiome. Aditionally recent inmmune oncology research has identified that certain gut bacteria are associated with response of lack of response to immune modifying treatment.\nUnderstanding the impact of the gut microbiome on medical treatment response in IBD patients and the identification of biomarkers for stratification of patients with regards to disease progression and treatment response is one of the priorities in the clinical research for IBD. Stool samples were collected from PROFILE (PRedicting Outcomes For Crohn's disease using a moLecular biomarker) cohort.  PROFILE was a multicentre, open-label, biomarker-stratified, randomised controlled trial that enrolled adults with newly diagnosed active Crohn's disease.\nThis project will have three specific aims: 1. Explore the role of the microbiome in treatment response and resolution of inflammation 2. Test the capacity of a microbiome-based classification algorithm to predict treatment response 3. Crossreplicate microbiome associations and predictive algorithms in an independent UK-based cohort (IBD-RESPONSE) Sequencing\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Crohn's disease is a chronic, relapsing form of inflammatory bowel disease (IBD) characterised by recurrent flares that can lead to progressive bowel damage. Convential drug therapies for IBD patients involve steroids treatment and advance biological immunomodulators to keep patients into remission. For newly diagnosed patients, disease progression and response to treatment is higly unpredictable however diverse studies suggest that earlier therapeutical intervention results in better clinical outcome and mitigates the need of surgical resection. There is a need for the identification of robust biomarkers that can predict treatment response to range of biologics used for treatment of IBD pathology. \nUnderstanding the impact of the gut microbiome on medical treatment response in IBD patients and the identification of biomarkers for stratification of patients with regards to disease progression and treatment response is one of the priorities IBD clinical research.\nIBD-RESPONSE aims to characterise microbial markers of treatment response and natural disease history in people living with IBD. Stool samples were collected from PROFILE (PRedicting Outcomes For Crohn's disease using a moLecular biomarker) cohort. PROFILE was a study set up to compare the impact of step-up or top-down therapy with biologics on disease outcomes on newly diagnosed active Crohn's disease.\nUsing metagenomic sequencing, we will characterise the bacterial microbiome of baseline and follow-up stool samples collected as part of PROFILE. Bacterial microbiome features will be correlated with treatment response across the two trial arms and natural history of disease. These data will also be used as a validation dataset for predictive models of treatment responsiveness, built as part of IBD-RESPONSE.\nThis project will have three specific aims: 1. Explore the role of the microbiome in treatment response and resolution of inflammation 2. Test the capacity of a microbiome-based classification algorithm to predict treatment response 3. Crossreplicate microbiome associations and predictive algorithms in an independent UK-based cohort (IBD-RESPONSE) Sequencing","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007959","title":"ACED__Targeted_NanoSeq_for_deep_subclonal_selection_in_ccRCC","description":"Targeted NanoSeq of ccRCC tumours to characterise their deep subclonal landscape and patterns of selection.","abstract":"This study will use Targeted NanoSeq of ccRCC tumours to characterise their deep subclonal landscape and patterns of selection.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007960","title":"Placenta_Trophoblast_Core_RNA_Managed_Access","description":"Study of the role of metabolism during trophoblast differentiation and invasion.","abstract":"In this project, we aim to characterise novel molecular mechanisms governing human early placentation. Specifically, we will study the role of metabolism during trophoblast differentiation and invasion, the placental epithelial like-cells. To achieve this, we will apply single-cell multi-omics approaches to a wide variety of in vitro placental models, such as trophoblast stem cells and trophoblast organoids (blastocyst-derived and tissue-derived).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007961","title":"Genomic_Integrity_and_Safety_of_Stem_cell_Therapy_in_haemoglobinopathies_including_Sickle_Cell_Disease_TargetedNanoseq","description":"This study will involve collecting blood samples from 100 patients with sickle cell disease and 100 matched controls. Granulocytes will be isolated and the DNA extracted. From this, several sequencing approaches will be applied to help better understand the mutational and selective pressures  on blood stem cells in sickle cell disease. We plan to do:\n- Targeted NanoSeq with maximal duplex coverage up to ~4000X (with a custom panel, TE-93170215 (SCD v1))\n- Standard or low-input WGS to get the germline context that may impact the above\n- If there are insufficient mutation calls from the targeted nanoseq, additional RE-NanoSeq may be applied to better define the mutation burdens and signatures.\nThis part of the study focuses on the targeted NanoSeq.","abstract":"Sickle cell disease (SCD) is an inherited disorder causing considerable morbidity and mortality due to polymerisation of sickle haemoglobin causing deformation of red cells and vaso-occlusion in multiple organs. It is associated with an increased risk of leukemia. Understanding the reasons behind this is particularly important as we move into an era where transplantation and cellular therapies are becoming increasingly utilized. We will be assessing mutational signatures and burdens in normal blood cells, as well as the burden of expanded clones harbouring driver mutations in patients with SCD. We will be comparing these to an age and ethnically matched control cohort (where possible) to better understand how SCD impacts the mutation landscape and clonal dynamics\nof the haematopoietic system.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007962","title":"High volume culture initiating in vitro evolution in neuroblastoma cell lines","description":"Despite the advent of advanced molecular prognostic tools, it is still difficult to predict the course of disease for cancer patients at the individual level. This lack of predictability is also reflected in many experimental cancer model systems, begging the question of whether certain biological aspects of cancer (eg. growth, evolution etc.) can ever be anticipated or if there remains an inherent unpredictability to cancer, similar to other complex biological systems. We demonstrate by a combination of agent-based mathematical modelling, analysis of patient-derived xenograft systems from multiple cancer types, and in-vitro culture that certain conditions may invoke chaotic fluctuations in the clonal landscape of cancer growth. Our findings indicate that under those conditions, the cancer genome may behave as a complex dynamic system, making its long-term evolution inherently unpredictable.","abstract":"Despite the advent of advanced molecular prognostic tools, it is still difficult to predict the course of disease for cancer patients at the individual level. This lack of predictability is also reflected in many experimental cancer model systems, begging the question of whether certain biological aspects of cancer (eg. growth, evolution etc.) can ever be anticipated or if there remains an inherent unpredictability to cancer, similar to other complex biological systems. We demonstrate by a combination of agent-based mathematical modelling, analysis of patient-derived xenograft systems from multiple cancer types, and in-vitro culture that certain conditions may invoke chaotic fluctuations in the clonal landscape of cancer growth. Our findings indicate that under those conditions, the cancer genome may behave as a complex dynamic system, making its long-term evolution inherently unpredictable.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007963","title":"Response_SLE","description":"a","abstract":"a","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007964","title":"Noorani__Oesophageal_Diseases_Targeted_Nanoseq","description":"Oesophageal cancer is the 6th most common cause of cancer death worldwide with an overall 5 year survival of 10-25%. State of the art sequencing technologies have demonstrated that canonical driver mutations occur in normal tissues across organ types, challenging traditional understanding of clonal evolution in cancer development and presenting the opportunity to detect hidden genomic alterations in tissues with an increased cancer risk. This study aims to comprehensively identify the genomic alterations in benign oesophageal diseases with an increased cancer risk, including Chagas mega-oesophagus in 200 cases. Through combined duplex sequencing and Laser Capture Microdissection we aim to reconstruct the landscape of these diseases in unprecedented deail.","abstract":"Comprehensive clonal analysis of oesophageal diseases with an increased cancer risk using Exome Nanoseq","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007965","title":"Noorani__Oesophageal_Diseases_Exome_Nanoseq","description":"Oesophageal cancer is the 6th most common cause of cancer death worldwide with an overall 5 year survival of 10-25%. State of the art sequencing technologies have demonstrated that canonical driver mutations occur in normal tissues across organ types, challenging traditional understanding of clonal evolution in cancer development and presenting the opportunity to detect hidden genomic alterations in tissues with an increased cancer risk. This study aims to comprehensively identify the genomic alterations in benign oesophageal diseases with an increased cancer risk, including Chagas mega-oesophagus in 200 cases. Through combined duplex sequencing and Laser Capture Microdissection we aim to reconstruct the landscape of these diseases in unprecedented deail.","abstract":"Comprehensive clonal analysis of oesophageal diseases with an increased cancer risk using Exome Nanoseq","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007966","title":"Double mutant DNMT3A AML: a unique subtype","description":"Mutation of DNMT3A, encoding a de novo methyltransferase essential for cytosine methylation, is a common early event in clonal hematopoiesis (CH) and adult acute myeloid leukemia (AML). Spontaneous deamination of methylated cytosines damages DNA, which is repaired by the base excision repair (BER) enzymes MBD4 and TDG. Congenital MBD4-deficiency has been linked to early-onset CH and AML, and is marked by exceedingly high levels of DNA damage and mutation of DNMT3A. Strikingly, wildtype (WT) DNMT3A binds TDG, thereby potentiating its repair activity. Since TDG is the only remaining BER enzyme in MBD4-deficient AML patients capable of repairing methylation damage, we investigated whether mutant DNMT3A negatively affects the repair function of TDG. We found that, whereas WT DNMT3A stimulates TDG function, mutant DNMT3A impairs TDG-mediated repair of DNA damage in vitro. In light of this finding and to extrapolate our observations to the broader AML patient population, we investigate here the genetic profiles and survival outcomes of AML patients with single (SM) versus double mutant (DM) DNMT3A. DM DNMT3A AML patients show a characteristic driver mutation landscape and reduced overall survival when compared to SM DNMT3A AML patients. Importantly, whole-genome sequencing showed a trend for increased DNA damage in primary DM DNMT3A AML samples, especially when DNMT3A mutations are located at the DNMT3A-TDG interaction interface.","abstract":"Mutation of DNMT3A, encoding a de novo methyltransferase essential for cytosine methylation, is a common early event in clonal hematopoiesis (CH) and adult acute myeloid leukemia (AML). Spontaneous deamination of methylated cytosines damages DNA, which is repaired by the base excision repair (BER) enzymes MBD4 and TDG. Congenital MBD4-deficiency has been linked to early-onset CH and AML, and is marked by exceedingly high levels of DNA damage and mutation of DNMT3A. Strikingly, wildtype (WT) DNMT3A binds TDG, thereby potentiating its repair activity. Since TDG is the only remaining BER enzyme in MBD4-deficient AML patients capable of repairing methylation damage, we investigated whether mutant DNMT3A negatively affects the repair function of TDG. We found that, whereas WT DNMT3A stimulates TDG function, mutant DNMT3A impairs TDG-mediated repair of DNA damage in vitro. In light of this finding and to extrapolate our observations to the broader AML patient population, we investigate here the genetic profiles and survival outcomes of AML patients with single (SM) versus double mutant (DM) DNMT3A. DM DNMT3A AML patients show a characteristic driver mutation landscape and reduced overall survival when compared to SM DNMT3A AML patients. Importantly, whole-genome sequencing showed a trend for increased DNA damage in primary DM DNMT3A AML samples, especially when DNMT3A mutations are located at the DNMT3A-TDG interaction interface.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-10-25T09:38:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001007967","title":"Transcriptomics-driven classification of ALAL","description":"Acute leukemia of ambiguous lineage (ALAL) is a rare, poor-prognosis subtype of acute leukemia that cannot be assigned to a single hematopoietic lineage. Although ALAL patients are typically treated with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) regimens, optimal treatment choice is hindered by their lineage ambiguity. Therefore, we investigated the added value of transcriptomics for improving lineage assignment, currently based mainly on surface markers. First, we used an in-house pipeline to comprehensively detect genetic lesions in RNA-sequencing data (n=23) with a sensitivity &gt;90%, as confirmed by targeted DNA sequencing. Second, we compared ALAL gene expression profiles (GEPs) with representative AML (n=145), B-ALL (n=223) and T-ALL (n=85) cases. In a principal component analysis, ALALs did not form a separate group, but clustered with AML, B-ALL or T-ALL. Accordingly, a machine learning classifier trained with GEPs of acute leukemias segregated 20/23 ALALs into myeloid-, B- or T-lymphoid leukemia. These 20 cases harbored genetic abnormalities consistent with the classifier-assigned leukemia. Furthermore, ALAL GEPs were deconvoluted with single-cell transcriptional profiles of normal hematopoietic cells using CIBERSORTx, revealing enrichment for signatures of lineages corresponding to the leukemic type predicted by our algorithm. The classifier was validated on an external ALAL cohort (n=24), assigning 75% of the patients to a lineage matching their immunophenotypic and methylation profiles. In conclusion, integrative analysis of RNA-sequencing data can accurately classify most ALAL cases. The pipeline and classifier developed in our study are valuable tools to improve ALAL diagnosis and guide therapeutic decisions.","abstract":"Acute leukemia of ambiguous lineage (ALAL) is a rare, poor-prognosis subtype of acute leukemia that cannot be assigned to a single hematopoietic lineage. Although ALAL patients are typically treated with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) regimens, optimal treatment choice is hindered by their lineage ambiguity. Therefore, we investigated the added value of transcriptomics for improving lineage assignment, currently based mainly on surface markers. First, we used an in-house pipeline to comprehensively detect genetic lesions in RNA-sequencing data (n=23) with a sensitivity &gt;90%, as confirmed by targeted DNA sequencing. Second, we compared ALAL gene expression profiles (GEPs) with representative AML (n=145), B-ALL (n=223) and T-ALL (n=85) cases. In a principal component analysis, ALALs did not form a separate group, but clustered with AML, B-ALL or T-ALL. Accordingly, a machine learning classifier trained with GEPs of acute leukemias segregated 20/23 ALALs into myeloid-, B- or T-lymphoid leukemia. These 20 cases harbored genetic abnormalities consistent with the classifier-assigned leukemia. Furthermore, ALAL GEPs were deconvoluted with single-cell transcriptional profiles of normal hematopoietic cells using CIBERSORTx, revealing enrichment for signatures of lineages corresponding to the leukemic type predicted by our algorithm. The classifier was validated on an external ALAL cohort (n=24), assigning 75% of the patients to a lineage matching their immunophenotypic and methylation profiles. In conclusion, integrative analysis of RNA-sequencing data can accurately classify most ALAL cases. The pipeline and classifier developed in our study are valuable tools to improve ALAL diagnosis and guide therapeutic decisions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-11-04T09:38:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007968","title":"HCA_Endometrium_Ferring_RNA","description":"improve current endometrial in vitro models by incorporating the macrophage cell lineage into robust co-cultures.","abstract":"\"This project aims to improve current endometrial in vitro models by incorporating the macrophage cell lineage into robust co-cultures. \nOur aims are to - 1) establish a co-culture model with endometrial organoids and tissue-resident macrophages 2) to replicate monocyte recruitment and differentiation into macrophages within endometrial co-cultures and 3) to determine the function and molecular mechanisms of endometrial macrophages. The single cell transcriptome sequencing data in this study is used to validate and interrogate our approaches in achieving these aims\n\"","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007969","title":"Dynamics of circulating tumor DNA in acute myeloid leukemia (AML) patients who undergo allogeneic transplantation","description":"Allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative option for many patients with acute myeloid leukemia (AML). With the increasing use of non-myeloablative conditioning regimens, it is widely assumed that the cytotoxic conditioning itself does not eradicate all leukemia cells. Instead, the donor-derived immune cells are believed to eliminate residual leukemia cells over time. This so-called graft-versus-leukemia (GvL) is postulated to be the primary mechanism by which allo-HCT achieves sustained remissions in patients with AML. However, the precise quantification of GvL effects and its contribution to leukemia eradication has not yet been demonstrated by sequential, highly sensitive measurements of residual disease at various time points following allo-HCT. In the current study, we employed a novel, highly sensitive and specific plasma-based assay to track mutations in the leukemia cells of 14 patients before and after allo-HCT. If the primary therapeutic benefit of allo-HCT is truly mediated through a GvL effect, we hypothesized that leukemia cells would persist following cytotoxic conditioning and would often be reduced after post-transplant immunosuppression was discontinued. In the majority of patients (11 of 14, 79%), the conditioning used for allo-HCT did not eradicate the leukemia cells. In seven of these 11 patients, the leukemia cells persisted until immunosuppression was discontinued, at which time the persistent leukemia cells were reduced or eradicated. These results demonstrate the feasibility of using circulating tumor DNA (ctDNA) as a dynamic marker of GvL as well as minimal residual disease for patients with AML undergoing alloHCT, and have substantial implications for their management.","abstract":"Allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative option for many patients with acute myeloid leukemia (AML). With the increasing use of non-myeloablative conditioning regimens, it is widely assumed that the cytotoxic conditioning itself does not eradicate all leukemia cells. Instead, the donor-derived immune cells are believed to eliminate residual leukemia cells over time. This so-called graft-versus-leukemia (GvL) is postulated to be the primary mechanism by which allo-HCT achieves sustained remissions in patients with AML. However, the precise quantification of GvL effects and its contribution to leukemia eradication has not yet been demonstrated by sequential, highly sensitive measurements of residual disease at various time points following allo-HCT. In the current study, we employed a novel, highly sensitive and specific plasma-based assay to track mutations in the leukemia cells of 14 patients before and after allo-HCT. If the primary therapeutic benefit of allo-HCT is truly mediated through a GvL effect, we hypothesized that leukemia cells would persist following cytotoxic conditioning and would often be reduced after post-transplant immunosuppression was discontinued. In the majority of patients (11 of 14, 79%), the conditioning used for allo-HCT did not eradicate the leukemia cells. In seven of these 11 patients, the leukemia cells persisted until immunosuppression was discontinued, at which time the persistent leukemia cells were reduced or eradicated. These results demonstrate the feasibility of using circulating tumor DNA (ctDNA) as a dynamic marker of GvL as well as minimal residual disease for patients with AML undergoing alloHCT, and have substantial implications for their management.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-11-04T14:58:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007970","title":"Bone marrow NK cells from individuals with multiple myeloma and controls","description":"Malignant plasma cells in multiple myeloma patients reside in the bone marrow and continuously interact with local immune cells. Progression and therapy response are influenced by this immune environment, highlighting the need for a detailed understanding of endogenous immune responses to malignant plasma cells. Here we used the 5TGM1 murine transfer model of multiple myeloma to dissect early immune responses to myeloma cells. We modeled stable and progressive disease by transferring 5TGM1 murine myeloma cells into C57Bl/6 mice and KaLwRij mice respectively. We used flow cytometry and single-cell and bulk transcriptomic analyses to characterize differential immune responses in stable and progressive disease. Transfer of 5TGM1 cells in C57Bl/6 mice led to stable disease with low tumor burden in a subset of animals. Stable disease was associated with sustained activation and expansion of NK cells, ILC1, and CD8+ T cells, a response that was lost upon disease progression. Single cell RNA-sequencing of immune cells and bulk RNA sequencing of immune and mesenchymal stromal cells implicated activation of interferon responses as a central immune pathway during stable disease. Experimentally, neutralization of IFNg significantly increased myeloma development and progression in C57Bl/6 mice, testifying to the importance of this pathway in early disease control. In conclusion, we provide a framework for studying immune responses to multiple myeloma progression in immunocompetent and genetically modifiable mice and highlight the importance of bone marrow immunity in tumor control.","abstract":"Malignant plasma cells in multiple myeloma patients reside in the bone marrow and continuously interact with local immune cells. Progression and therapy response are influenced by this immune environment, highlighting the need for a detailed understanding of endogenous immune responses to malignant plasma cells. Here we used the 5TGM1 murine transfer model of multiple myeloma to dissect early immune responses to myeloma cells. We modeled stable and progressive disease by transferring 5TGM1 murine myeloma cells into C57Bl/6 mice and KaLwRij mice respectively. We used flow cytometry and single-cell and bulk transcriptomic analyses to characterize differential immune responses in stable and progressive disease. Transfer of 5TGM1 cells in C57Bl/6 mice led to stable disease with low tumor burden in a subset of animals. Stable disease was associated with sustained activation and expansion of NK cells, ILC1, and CD8+ T cells, a response that was lost upon disease progression. Single cell RNA-sequencing of immune cells and bulk RNA sequencing of immune and mesenchymal stromal cells implicated activation of interferon responses as a central immune pathway during stable disease. Experimentally, neutralization of IFNg significantly increased myeloma development and progression in C57Bl/6 mice, testifying to the importance of this pathway in early disease control. In conclusion, we provide a framework for studying immune responses to multiple myeloma progression in immunocompetent and genetically modifiable mice and highlight the importance of bone marrow immunity in tumor control.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007971","title":"Chemo_liver_zonation","description":"Exome nanoseq of laser capture microdissected hepatocyte zones in patients with and without chemotherapy exposure.","abstract":"Assessing impact of chemotherapy metabolism on the driver landscape in liver tissue.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007972","title":"Masld_spectrum_targeted_nanoseq","description":"Targeted NanoSeq of MASLD across the disease spectrum.","abstract":"Part of the development of the chronic liver disease somatic mutational atlas - studying the adaptive mutational pathways developed by hepatocytes on their path towards end-stage liver disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007973","title":"Impact_of_patient_specific_factors_on_the_cellular_fitness_of_somatic_alterations_in_human_kidneys___WGS","description":"This is a collaborative project that aims to understand which processes are driving tumour growth. We have identified a large cohort of patients who have longitudinal growth data prior to surgery. By linking phylogenetic reconstruction with growth, we can then calculate the relative fitness advantage of both somatic events and patient specific risk factors.","abstract":"Through multiregional whoel genome sequencing and targeted duplex sequencing of a large range of kidney cancers with longitunal growth data, we aim to: \n•\tAccurately determine the fitness of driver mutations within a single tumour by relating tumour phylogenomic reconstruction and volumetric tumour growth \n•\tExplain the variance in fitness of common driver mutations \n•\tPredict tumour future behaviour or assess the benefit of preventative strategies?","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007974","title":"Impact_of_patient_specific_factors_on_the_cellular_fitness_of_somatic_alterations_in_human_kidneys___RNA","description":"This is a collaborative project that aims to understand which processes are driving tumour growth. We have identified a large cohort of patients who have longitudinal growth data prior to surgery. By linking phylogenetic reconstruction with growth, we can then calculate the relative fitness advantage of both somatic events and patient specific risk factors.","abstract":"Through multiregional whoel genome sequencing and targeted duplex sequencing of a large range of kidney cancers with longitunal growth data, we aim to: \n•\tAccurately determine the fitness of driver mutations within a single tumour by relating tumour phylogenomic reconstruction and volumetric tumour growth \n•\tExplain the variance in fitness of common driver mutations \n•\tPredict tumour future behaviour or assess the benefit of preventative strategies?","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007975","title":"ASD","description":"Autism spectrum disorder (ASD) is an increasingly recognized childhood developmental disability. We use LRS to interrogate the methylation pattern associated with the SVs and phase the SV haplotypes to further clarify their contribution to disorder. LRS allows insight into the genome and methylome that allow us to uncover variant complexity and contribution that was previously unseen with SRS. Ultimately, this furthers precision diagnosis and contributes to individualized treatment for affected individuals and their families within the clinic.","abstract":"Autism spectrum disorder (ASD) is an increasingly recognized childhood developmental disability. We use LRS to interrogate the methylation pattern associated with the SVs and phase the SV haplotypes to further clarify their contribution to disorder. LRS allows insight into the genome and methylome that allow us to uncover variant complexity and contribution that was previously unseen with SRS. Ultimately, this furthers precision diagnosis and contributes to individualized treatment for affected individuals and their families within the clinic.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007976","title":"HCA_Blood_Disease_Atopic_Dermatitis_BEACONomics_DNA_Managed_Access","description":"Defining the spatial transcriptome and cell-cell interactions in atopic dermatitis skin","abstract":"Atopic eczema (eczema) is the most common inflammatory skin disease, with a lifetime prevalence of 10-15% and the leading cause of disease burden conferred by skin disease. Eczema drugs targeting Th2 immune mediators have recently been approved, including the biologic Dupilumab and Janus Kinase (JAK) inhibitors. However, the response is highly heterogeneous, meaning patients often cycle through multiple drugs for disease control. Understanding the molecular drivers of treatment response is necessary to shift from trial-and-error to data-driven drug allocation, to optimise efficacy, reduce time to remission, avoid treatment switches, drug-related morbidity and improve cost effectiveness. The BEACON eczema drug trial will be the largest platform trial worldwide to directly compare the effectiveness and tolerability of standard and targeted eczema drugs. The mechanistic BEACON-omics study will utilise longitudinal single-cell multiomics and spatial genomics skin profiling of samples collected from carefully phenotyped patients (using gold standard clinical outcomes) of responders and non-responders from each of the BEACON treatment arms (dupilumab, JAK1 inhibitor and methotrexate) to identify novel mechanisms of drug action in these patients, which will inform drug innovation efforts and pave the way for future target discovery.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007977","title":"Defining_The_Biological_Basis_Of_Staphylococcus_Aureus_Carriage","description":"Staphylococcus aureus is a major cause of infection worldwide. This bacterium persistently colonises the nose (its natural niche) in around 20% of the population, which increases their risk of S. aureus infection. Why some people carry S. aureus while others never do is not understood, but is likely to reflect a complex trait influenced by multiple factors. This may include the human genome, host immunity, the nasal microbiota, bacterial-nasal epithelial cell interactions and lifestyle choices. We propose that key determinants for S. aureus carriage can be defined in a powered cohort study in which these parameters are established.","abstract":"Staphylococcus aureus is a major cause of infection worldwide. This bacterium persistently colonises the nose (its natural niche) in around 20% of the population, which increases their risk of S. aureus infection. Why some people carry S. aureus while others never do is not understood, but is likely to reflect a complex trait influenced by multiple factors. This may include the human genome, host immunity, the nasal microbiota, bacterial-nasal epithelial cell interactions and lifestyle choices. We propose that key determinants for S. aureus carriage can be defined in a powered cohort study in which these parameters are established. Our study will capitalise on an existing cohort (INTERVAL) of healthy volunteers who have been extensively characterised through human genome sequencing and phenotypic profiling. We will screen 25,000 INTERVAL participants for S. aureus carriage, and using sequencing methods define their nasal microbiota composition. We will use existing as well as generate additional data on lifestyle. These datasets will be mined during a series of genome-wide and phenotypic association studies to identify factors that influence the nasal microbiota and S. aureus carrier status. Selected phenotypic and genetic variants of interest will then be tested in relevant experimental systems.","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007978","title":"LiFTS___Trecandis_Seq","description":"Single analysis of patients with Li_fraumeni Syndrome using a novel multi-omic single cell approach , Trencandis-Seq, that allow simultaneous analysis of mutations and transcriptome.","abstract":"Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with high risks for a broad spectrum of cancers including early-onset cancers. The lifetime risks of cancer for women and men with  LFS are 90% and 70%, respectively, with 50% of cancers occur prior to age 40 years. \nLFS is associated with a germline pathogenic variant in TP53 gene, however the mechanism by which the mutation causes malignant transformation are still unknown. \nIn this study multiple tissues from LFS patients will be analysed using a novel single cell multi omic approach that allow simultaneous  profiling of genotype, transcriptome profiling and cellular enabling to better understand the functional consequences of TP53 mutations and their role in driving malignant transformation.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007979","title":"Molecular_Profiles_and_Genetic_Origins_of_Ancestral_Phenotypic_Diversity_in_SLE__Whole_Genome_sequencing","description":"This cohort comprises patients with systemic lupus erythematosus (SLE) who were recruited from several sites across the UK and Australia including King’s College Hospital NHS Foundation Trust, Guy's and St Thomas' NHS Foundation Trust, Imperial College Healthcare NHS Trust and the Monash Lupus Clinic, Melbourne. Individuals with self-reported African or Afro-Caribbean, European, East Asian, Indigenous Australian, and South Asian ancestries were prioritised for recruitment. Whole blood samples from 420 SLE patients and 90 healthy donors have been collected for DNA extraction and whole genome sequencing. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Systemic lupus erythematosus (SLE) is a complex, multisystem autoimmune disease with a highly hetergoenous clinical presentation. The prevalence of SLE is higher in many non-European populations and genetic ancestry has been shown to influence disease severity, organ involvement and response to treatment. Patients with SLE and healthy controls were recruited from sites across the UK and Australia, and samples collected for functional genomics analysis to understand the molecular mechanisms and genetic factors contributing to heterogeneity in disease presentation.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007980","title":"Molecular_Profiles_and_Genetic_Origins_of_Ancestral_Phenotypic_Diversity_in_SLE__RNA_sequencing","description":"This cohort comprises patients with systemic lupus erythematosus (SLE) who were recruited from several sites across the UK and Australia including King’s College Hospital NHS Foundation Trust, Guy's and St Thomas' NHS Foundation Trust, Imperial College Healthcare NHS Trust and the Monash Lupus Clinic, Melbourne. Individuals with self-reported African or Afro-Caribbean, European, East Asian, Indigenous Australian, and South Asian ancestries were prioritised for recruitment. Whole blood samples from 610 SLE patients and 90 healthy donors have been collected for RNA extraction and bulk RNA-sequencing. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Systemic lupus erythematosus (SLE) is a complex, multisystem autoimmune disease with a highly hetergoenous clinical presentation. The prevalence of SLE is higher in many non-European populations and genetic ancestry has been shown to influence disease severity, organ involvement and response to treatment. Patients with SLE and healthy controls were recruited from sites across the UK and Australia, and samples collected for functional genomics analysis to understand the molecular mechanisms and genetic factors contributing to heterogeneity in disease presentation.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007981","title":"Spatial transcriptomics analysis of HPV-dependent and HPV-independent vulval squamous cell carcinoma","description":"In this study we have used sequencing-based spatial transcriptomics (ST) optimised for FFPE tissue to investigate gene expression in a cohort of HPVi and HPVd VSCC, including assessment of pre-invasive LS, HSIL and DVIN and associated inflammation. Our data indicate significant differences in gene expression between VSCC of different aetiologies, with marked differences in immune-related gene expression both within the invasive disease and in peri-tumoural inflammatory areas.","abstract":"In this study we have used sequencing-based spatial transcriptomics (ST) optimised for FFPE tissue to investigate gene expression in a cohort of HPVi and HPVd VSCC, including assessment of pre-invasive LS, HSIL and DVIN and associated inflammation. Our data indicate significant differences in gene expression between VSCC of different aetiologies, with marked differences in immune-related gene expression both within the invasive disease and in peri-tumoural inflammatory areas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-11-13T13:24:59+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007982","title":"CD4_CD8_single_cell_CRISPR_profiling","description":"Step 1: pilot CRISPR screen with scRNA-seq readout (10 targets, 10x with GEX, CRISPR guide and citeseq libraries - we will also require 1 test sample for long read with PACBBio).\n\nStep 2: main screen (100s targets, 10x with GEX, CRISPR guide and citeseq libraries)\nCD4+ or CD8+ T cells are isolated from the blood of healthy individuals, expanded in vitro and edited using either CRISPRko orCRISPR activation. After selection, cells were re-stimulated at day 10 and collected at different time points after restimulation. Samples were pooled together with cell hashing then stained with CITE-seq TotalSeq cocktail and loaded on a ChromiumX for single-cell transcriptomics. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"CD4+ and CD8+ T cells are lymphoid cells playing a key role in the immune response. In the scope of this project, we will isolate these cells from healthy individuals, perturb hundreds of genes using CRISPR tools, and subsequently assess the impact on transcriptomics at a single-cell upon stimulation. Dat will be used to better understand the effect of these disease\nassociated genes on T cell function.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007983","title":"Molecular_Profiles_and_Genetic_Origins_of_Ancestral_Phenotypic_Diversity_in_SLE__RNA_sequencing","description":"This cohort comprises patients with systemic lupus erythematosus (SLE) who were recruited from several sites across the UK and Australia including King’s College Hospital NHS Foundation Trust, Guy's and St Thomas' NHS Foundation Trust, Imperial College Healthcare NHS Trust and the Monash Lupus Clinic, Melbourne. Individuals with self-reported African or Afro-Caribbean, European, East Asian, Indigenous Australian, and South Asian ancestries were prioritised for recruitment. Whole blood samples from 610 SLE patients and 90 healthy donors have been collected for RNA extraction and bulk RNA-sequencing. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Systemic lupus erythematosus (SLE) is a complex, multisystem autoimmune disease with a highly hetergoenous clinical presentation. The prevalence of SLE is higher in many non-European populations and genetic ancestry has been shown to influence disease severity, organ involvement and response to treatment. Patients with SLE and healthy controls were recruited from sites across the UK and Australia, and samples collected for functional genomics analysis to understand the molecular mechanisms and genetic factors contributing to heterogeneity in disease presentation.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007984","title":"Molecular_Profiles_and_Genetic_Origins_of_Ancestral_Phenotypic_Diversity_in_SLE__Whole_Genome_sequencing","description":"This cohort comprises patients with systemic lupus erythematosus (SLE) who were recruited from several sites across the UK and Australia including King’s College Hospital NHS Foundation Trust, Guy's and St Thomas' NHS Foundation Trust, Imperial College Healthcare NHS Trust and the Monash Lupus Clinic, Melbourne. Individuals with self-reported African or Afro-Caribbean, European, East Asian, Indigenous Australian, and South Asian ancestries were prioritised for recruitment. Whole blood samples from 420 SLE patients and 90 healthy donors have been collected for DNA extraction and whole genome sequencing. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Systemic lupus erythematosus (SLE) is a complex, multisystem autoimmune disease with a highly hetergoenous clinical presentation. The prevalence of SLE is higher in many non-European populations and genetic ancestry has been shown to influence disease severity, organ involvement and response to treatment. Patients with SLE and healthy controls were recruited from sites across the UK and Australia, and samples collected for functional genomics analysis to understand the molecular mechanisms and genetic factors contributing to heterogeneity in disease presentation.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007985","title":"CDK4/6 inhibition in advanced chordoma: final results of the NCT PMO-1601","description":"Background. Chordoma is a rare bone tumor with no approved systemic therapy. Inactivation of the tumor suppressor p16 (encoded by CDKN2A) leads to aberrant cyclin D-CDK4/6-RB pathway activity, which can be inhibited by palbociclib in chordoma cell lines.\nPatients and Methods. We conducted a phase II single-arm, open-labeled trial on palbociclib in adult patients with advanced chordomas with p16 loss (by immunohistochemistry) or CDKN2A loss (by genomic analysis) and CDK4/6 and RB1 presence (by immunohistochemistry or RNA-Sequencing). Patients received 125mg palbociclib once daily for 21 days in a 28-day cycle. The study used a Simon optimal 2-stage design. The primary endpoint was disease control rate after six cycles. Response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints included progression-free survival, overall survival, and biomarker analysis. The study was considered positive if 25% of patients reached the primary endpoint. \nResults. Between December 2017 and April 2023, 28 patients (median age 60 years, range 31-84) were enrolled. After a median follow-up of 28 months, the disease control rate was 39%, with 11 out of 28 patients achieving stable disease. No objective responses were observed. The median progression-free survival was 5.6 months, and the median overall survival was 24.6 months. Treatment was well tolerated without new safety signals. CDKN2A deletions were the most common genomic alterations underlying p16 loss and were accompanied by MTAP co-deletion. There was no correlation between responder phenotypes by immunohistochemistry and outcome. RNA-based analysis showed heterogeneous pathways deregulation at study entry suggesting underlying primary resistance mechanisms\nConclusion. This trial met its primary endpoint with a 39% disease control rate, though antitumor activity was modest. Molecularly tailored combination therapies should be considered to improve efficacy. (ClinicalTrials.gov number, NCT03110744).","abstract":"Background. Chordoma is a rare bone tumor with no approved systemic therapy. Inactivation of the tumor suppressor p16 (encoded by CDKN2A) leads to aberrant cyclin D-CDK4/6-RB pathway activity, which can be inhibited by palbociclib in chordoma cell lines.\nPatients and Methods. We conducted a phase II single-arm, open-labeled trial on palbociclib in adult patients with advanced chordomas with p16 loss (by immunohistochemistry) or CDKN2A loss (by genomic analysis) and CDK4/6 and RB1 presence (by immunohistochemistry or RNA-Sequencing). Patients received 125mg palbociclib once daily for 21 days in a 28-day cycle. The study used a Simon optimal 2-stage design. The primary endpoint was disease control rate after six cycles. Response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints included progression-free survival, overall survival, and biomarker analysis. The study was considered positive if 25% of patients reached the primary endpoint. \nResults. Between December 2017 and April 2023, 28 patients (median age 60 years, range 31-84) were enrolled. After a median follow-up of 28 months, the disease control rate was 39%, with 11 out of 28 patients achieving stable disease. No objective responses were observed. The median progression-free survival was 5.6 months, and the median overall survival was 24.6 months. Treatment was well tolerated without new safety signals. CDKN2A deletions were the most common genomic alterations underlying p16 loss and were accompanied by MTAP co-deletion. There was no correlation between responder phenotypes by immunohistochemistry and outcome. RNA-based analysis showed heterogeneous pathways deregulation at study entry suggesting underlying primary resistance mechanisms\nConclusion. This trial met its primary endpoint with a 39% disease control rate, though antitumor activity was modest. Molecularly tailored combination therapies should be considered to improve efficacy. (ClinicalTrials.gov number, NCT03110744).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-12-01T12:14:59.928661+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007986","title":"Aberrant RNA-splicing (neojunctions) offers a new source for targets, and our neoantigen discovery platform (SNIPP) characterizes a novel class of clonally-expressed splicing-derived neoantigens that elicit a CD8+ T-cell-mediated tumor killing response.","description":"RESULTS: Our pipeline identified 789 public neojunctions, with 32 neojunctions concurrently identified in transcriptomic and proteomic glioma data and predicted to be presented by HLA-A*02:01 with high confidence. IVS and subsequent 10x VDJ scRNA-seq identified TCR clonotypes reactive against neojunctions in RPL22 (n=7) and GNAS (n=1), the latter being highly intratumorally-conserved (detected in &gt; 90% of spatially-mapped biopsies across 17/56 patients (26.78%)). TCR-transduced T-cells demonstrated recognition and immunogenic activation against endogenously processed and presented neoantigens in multiple GBM PDX cell lines. Furthermore, IDH1-mutant oligodendroglioma samples demonstrated significantly elevated expression of neojunctions over IDH1-mutant astrocytoma and IDH1wt subtypes. Differential gene expression (DESeq2) identified decreased expression of splicing factors due to oligodendroglioma-specific co-deletion of Chromosomes 1p/19q. siRNA knockdown of these splicing factors (e.g. SF3A3, SNRPD2) in IDH1wt glioma cells resulted in significantly increased expression of corresponding neojunctions.","abstract":"RESULTS: Our pipeline identified 789 public neojunctions, with 32 neojunctions concurrently identified in transcriptomic and proteomic glioma data and predicted to be presented by HLA-A*02:01 with high confidence. IVS and subsequent 10x VDJ scRNA-seq identified TCR clonotypes reactive against neojunctions in RPL22 (n=7) and GNAS (n=1), the latter being highly intratumorally-conserved (detected in &gt; 90% of spatially-mapped biopsies across 17/56 patients (26.78%)). TCR-transduced T-cells demonstrated recognition and immunogenic activation against endogenously processed and presented neoantigens in multiple GBM PDX cell lines. Furthermore, IDH1-mutant oligodendroglioma samples demonstrated significantly elevated expression of neojunctions over IDH1-mutant astrocytoma and IDH1wt subtypes. Differential gene expression (DESeq2) identified decreased expression of splicing factors due to oligodendroglioma-specific co-deletion of Chromosomes 1p/19q. siRNA knockdown of these splicing factors (e.g. SF3A3, SNRPD2) in IDH1wt glioma cells resulted in significantly increased expression of corresponding neojunctions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007987","title":"Stratton__WGS___human_non_malignant_colon","description":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. This study will explore the methylation landscape of normal colonic crypts with and without Colibactin exposure.","abstract":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. This study will explore the methylation landscape of normal colonic crypts with and without Colibactin exposure.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007988","title":"Stratton__WGMS___human_non_malignant_colon","description":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. This study will explore the methylation landscape of normal colonic crypts with and without Colibactin exposure. ","abstract":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. This study will explore the methylation landscape of normal colonic crypts with and without Colibactin exposure.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007989","title":"NF1_Cambridge_Behjati_WellcomeCore_WGS","description":"We have shown that histologically normal tissues from patients with neurofibromatosis exhibit frequent second hits that inactivate the wild-type NF1 allele (work under review). Inactivation of both copies of NF1, therefore, is not sufficient to transform a tissue to malignancy. Previous studies, however, have found the inactivation of both copies of NF1 to be the only discernible driver events in certain low grade tumours. This raises the question, therefore, as to why two hits sometimes transform a cell to a low grade tumour and sometimes do not. We hope to resolve this through a multiomic study that compares histologically normal cells with two NF1 hits with tumours with two NF1 hits.","abstract":"We have shown that histologically normal tissues from patients with neurofibromatosis exhibit frequent second hits that inactivate the wild-type NF1 allele (work under review). Inactivation of both copies of NF1, therefore, is not sufficient to transform a tissue to malignancy. Previous studies, however, have found the inactivation of both copies of NF1 to be the only discernible driver events in certain low grade tumours. This raises the question, therefore, as to why two hits sometimes transform a cell to a low grade tumour and sometimes do not. We hope to resolve this through a multiomic study that compares histologically normal cells with two NF1 hits with tumours with two NF1 hits.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007990","title":"Orphan_Tumour_Study_NB_RNA","description":"The aim of this study is to investigate the transcriptional landscape of human cancer.","abstract":"The aim of this study is to investigate the transcriptional landscape of human cancer.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007991","title":"DeepCell","description":"Generate a perturbation atlas on colorectal organoids to investigate cellular plasticity at the single cell level.","abstract":"Generate a perturbation atlas on colorectal organoids to investigate cellular plasticity at the single cell level.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007992","title":"NPM1_Positive_Acute_Myeloid_Leukaemia_Development_WGS","description":"Bone marrow samples were obtained from four patients with NPM1 positive acute myeloid leukaemia at three timepoints, namely at diagnosis, after induction of remission and at relapse. By undertaking whole genome sequencing of these samples, and establishing the mutational burden at each stage, we hope to delineate the way cells transition from pre-leukaemia to leukaemia and approximate how long this takes.","abstract":"Bone marrow samples were obtained from four patients with NPM1 positive acute myeloid leukaemia at three timepoints, namely at diagnosis, after induction of remission and at relapse. By undertaking whole genome sequencing of these samples, and establishing the mutational burden at each stage, we hope to delineate the way cells transition from pre-leukaemia to leukaemia and approximate how long this takes.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007993","title":"Myeloid_Malignancies_in_patients_with_TBD_WES","description":"A cohort of patients with telomere biology disorders (TBD) with a known genetic basis. TBD patients commonly develop clonal haematopoiesis driven by rescue mutations that mitigate the effect of a shortened telomere. These people can then develop myeloid malignancies like myelodysplastic syndromes and acute myeloid leukaemia. Here, we will search for such mutations to understand how they rescue short telomeres and how they lead to myeloid malignancies.","abstract":"A cohort of patients with telomere biology disorders (TBD) with a known genetic basis. TBD patients commonly develop clonal haematopoiesis driven by rescue mutations that mitigate the effect of a shortened telomere. These people can then develop myeloid malignancies like myelodysplastic syndromes and acute myeloid leukaemia. Here, we will search for such mutations to understand how they rescue short telomeres and how they lead to myeloid malignancies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007994","title":"Molecular_Profiles_and_Genetic_Origins_of_Ancestral_Phenotypic_Diversity_in_SLE__RNA_sequencing","description":"This cohort comprises patients with systemic lupus erythematosus (SLE) who were recruited from several sites across the UK and Australia including King’s College Hospital NHS Foundation Trust, Guy's and St Thomas' NHS Foundation Trust, Imperial College Healthcare NHS Trust and the Monash Lupus Clinic, Melbourne. Individuals with self-reported African or Afro-Caribbean, European, East Asian, Indigenous Australian, and South Asian ancestries were prioritised for recruitment. Whole blood samples from 610 SLE patients and 90 healthy donors have been collected for RNA extraction and bulk RNA-sequencing. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Systemic lupus erythematosus (SLE) is a complex, multisystem autoimmune disease with a highly hetergoenous clinical presentation. The prevalence of SLE is higher in many non-European populations and genetic ancestry has been shown to influence disease severity, organ involvement and response to treatment. Patients with SLE and healthy controls were recruited from sites across the UK and Australia, and samples collected for functional genomics analysis to understand the molecular mechanisms and genetic factors contributing to heterogeneity in disease presentation.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007995","title":"Molecular_Profiles_and_Genetic_Origins_of_Ancestral_Phenotypic_Diversity_in_SLE__Whole_Genome_sequencing","description":"This cohort comprises patients with systemic lupus erythematosus (SLE) who were recruited from several sites across the UK and Australia including King’s College Hospital NHS Foundation Trust, Guy's and St Thomas' NHS Foundation Trust, Imperial College Healthcare NHS Trust and the Monash Lupus Clinic, Melbourne. Individuals with self-reported African or Afro-Caribbean, European, East Asian, Indigenous Australian, and South Asian ancestries were prioritised for recruitment. Whole blood samples from 420 SLE patients and 90 healthy donors have been collected for DNA extraction and whole genome sequencing. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Systemic lupus erythematosus (SLE) is a complex, multisystem autoimmune disease with a highly hetergoenous clinical presentation. The prevalence of SLE is higher in many non-European populations and genetic ancestry has been shown to influence disease severity, organ involvement and response to treatment. Patients with SLE and healthy controls were recruited from sites across the UK and Australia, and samples collected for functional genomics analysis to understand the molecular mechanisms and genetic factors contributing to heterogeneity in disease presentation.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007996","title":"WGS_CML_Blast_Crisis_Bulk_Sorts","description":"The mutational landscape of specific flow sorted haematopoietic cell populations will be characterized by WGS.","abstract":"The mutational landscape of specific flow sorted haematopoietic cell populations will be characterized by WGS. Samples have been sourced from CBSB.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007997","title":"LCMB_WGS_LCH_Bulk","description":"The mutational landscape of specific flow sorted haematopoietic cell populations from LCH patients will be characterized by WGS.","abstract":"The mutational landscape of specific flow sorted haematopoietic cell populations from LCH patients will be characterized by WGS. Samples have been sourced from Newcastle University.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001007998","title":"MethylationEPIC BeadChip samples of pre- and post-5ZA-treated head and neck cancer patients refractory to anto-PD-1 therapy","description":"Background\nImmune checkpoint blockade (ICB) is an effective treatment in a subset of patients diagnosed with head and neck squamous cell carcinoma (HNSCC); however, most patients are refractory.\n\nMethods\nIn a non-randomized, open-label phase 1b clinical trial, participants with recurrent and/or metastatic (R/M) HNSCC were treated with low-dose 5’azacytidine (5’aza) daily for either 5- or 10-days in combination with fixed doses of durvalumab and tremelimumab after progression on ICB therapy. The primary objective was to assess the biologically effective dose of 5’aza as determined by molecular changes in paired baseline and on-treatment tumor biopsies; the secondary objective was safety. \n\nResults\nThirty-eight percent (3/8) of participants with evaluable paired tissue samples had a greater than 2-fold increase from baseline in interferon-gamma (IFN-ɣ) signature and CD274 (programmed cell death protein 1 ligand, PD-L1) expression within the tumor microenvironment (TME), which was associated with increased CD8+ T cell infiltration and decreased infiltration of CD4+ T regulatory cells. The mean neutrophil-to-lymphocyte ratio (NLR) decreased by greater than 50%, from 14.2 (SD 22.6) to 6.9 (SD 5.2). Median overall survival (OS) was 16.3 months (95% CI 1.9, NA) and 2-year OS rate was 24.7% (95% CI: 4.5%, 53.2%) with 58% (7/12) of treated participants demonstrated prolonged OS of greater than 12 months. \n\nConclusion\nOur findings suggest that low-dose 5’aza can reprogram systemic host immune responses and the local TME to increase IFN-ɣ and PD-L1 expression. The increased expression of these established biomarkers correlated with prolonged OS upon re-challenge with ICB.","abstract":"Background\nImmune checkpoint blockade (ICB) is an effective treatment in a subset of patients diagnosed with head and neck squamous cell carcinoma (HNSCC); however, most patients are refractory.\n\nMethods\nIn a non-randomized, open-label phase 1b clinical trial, participants with recurrent and/or metastatic (R/M) HNSCC were treated with low-dose 5’azacytidine (5’aza) daily for either 5- or 10-days in combination with fixed doses of durvalumab and tremelimumab after progression on ICB therapy. The primary objective was to assess the biologically effective dose of 5’aza as determined by molecular changes in paired baseline and on-treatment tumor biopsies; the secondary objective was safety. \n\nResults\nThirty-eight percent (3/8) of participants with evaluable paired tissue samples had a greater than 2-fold increase from baseline in interferon-gamma (IFN-ɣ) signature and CD274 (programmed cell death protein 1 ligand, PD-L1) expression within the tumor microenvironment (TME), which was associated with increased CD8+ T cell infiltration and decreased infiltration of CD4+ T regulatory cells. The mean neutrophil-to-lymphocyte ratio (NLR) decreased by greater than 50%, from 14.2 (SD 22.6) to 6.9 (SD 5.2). Median overall survival (OS) was 16.3 months (95% CI 1.9, NA) and 2-year OS rate was 24.7% (95% CI: 4.5%, 53.2%) with 58% (7/12) of treated participants demonstrated prolonged OS of greater than 12 months. \n\nConclusion\nOur findings suggest that low-dose 5’aza can reprogram systemic host immune responses and the local TME to increase IFN-ɣ and PD-L1 expression. The increased expression of these established biomarkers correlated with prolonged OS upon re-challenge with ICB.","study_type":"Other","pubmed_ids":[40091844],"external_links":null,"is_released":true,"released_date":"2024-12-10T15:46:30+01:00","is_deprecated":false},
{"accession_id":"EGAS00001007999","title":"Sequencing_tonsil_epithelium","description":"Tonsils can undergo long term chronic inflammation.  We wish to investigate if/how this impacts the epithelia landscape.  Tonsils from patients undergoing tonsillectomy will be collected and the epithelia removed.  The epithelia will be dissected into 2mm2 grids and sequenced at high depth using a targeted bait panel.","abstract":"Tonsils can undergo long term chronic inflammation.  We wish to investigate if/how this impacts the epithelia landscape.  Tonsils from patients undergoing tonsillectomy will be collected and the epithelia removed.  The epithelia will be dissected into 2mm2 grids and sequenced at high depth using a targeted bait panel.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008000","title":"UTSW_viral_hepatitis","description":"Whole Exome and Targeted NanoSeq of donors with exposure to viral hepatitis (HBV/HCV) to establish the driver landscape in this specific aetiology.","abstract":"Part of the development of the chronic liver disease somatic mutational atlas - studying the adaptive mutational pathways developed by hepatocytes on their path towards end-stage liver disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008001","title":"Stratton__WGS___RCC___Japan","description":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies.","abstract":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-12-13T08:52:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008002","title":"Single-cell spatial analysis of pediatric high-grade glioma reveals a novel population of immunosuppressive and tumor-promoting SPP1+/GPNMB+ myeloid cells","description":null,"abstract":"Pediatric-type diffuse high-grade gliomas (pHGG) are the leading cause of pediatric cancer-related deaths. Immunotherapy recently emerged as a promising novel treatment opportunity, but so far, clinical responses remain limited to only a small proportion of pHGG patients. Therefore, more insights into the pHGG’s tumor immune microenvironment, the target of immunotherapy, are urgently needed. As emerging evidence in other cancers points to the spatial architecture of the tumor immune microenvironment as a major determinant of therapeutic efficacy, we employed single-cell spatial analysis at the proteomic and transcriptomic level by combining cyclical immunofluorescence imaging and Spatial Molecular Imaging. We analyzed 32 patient-derived pHGG samples assembled into a tissue microarray and mapped their single-cell spatial landscapes. Our findings revealed that the tumor immune microenvironment is dominated by myeloid cells, including brain-resident microglia and monocyte-derived macrophages, with limited T cells. A large proportion of these myeloid cells expressed mesenchymal-like genes and were found to be positive for SPP1 and GPNMB. Spatial analysis uncovered that these cells were positioned close to mesenchymal-like tumor cells, but negatively correlated with the location of CD8+ T cells. SPP1+/GPNMB+ cells express genes related to immunosuppression and epithelial-to-mesenchymal transition, suggesting that SPP1+/GPNMB+ cells are an important component of the immunosuppressive tumor microenvironment of pHGG, and may serve as a potential novel therapeutic target.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008003","title":"WGS_of_matched_blood__Deep_subclonal_selection_in_ccRCC__IARC__","description":"WGS of matched normal samples from ccRCC patients to aid variant calling and copy number characterisation. This will be used to interpret Targeted NanoSeq data characterising their deep subclonal landscape and patterns of selection.","abstract":"This study will involve WGS of a set of ccRCC tumours and their matched normals to identify copy number changes. This will put into context the Targeted NanoSeq data characterising their deep subclonal landscape and patterns of selection.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008004","title":"Fragmentation signatures in cancer patients are similar to those in patients with vascular and autoimmune diseases","description":"The analysis of fragmentation patterns in plasma cell-free DNA (cfDNA) has been shown to distinguish individuals with cancer from healthy controls in multiple case-controlled studies. However, there have been few studies that investigate various types cfDNA fragmentomics patterns in individuals with other diseases. For this purpose, we developed a comprehensive metric, called fragmentation signatures, that integrated the distributions of fragment positioning, fragment length, and fragment end-motifs. Using this metric, we found that individuals with venous thromboembolism, systemic lupus erythematosus, dermatomyositis, or scleroderma had cfDNA fragmentation signatures that closely mimicked those found in individuals with advanced cancers. Furthermore, these signatures were highly correlated with increases in inflammatory markers in the blood. Though these data put substantial limitations on the specificity of fragmentomics-based tests for cancer diagnostics, they also offer ways to improve the interpretability of such tests. Moreover, they should lead to a better understanding of the cells – most likely inflammatory cells - from which plasma cfDNA is derived.","abstract":"The analysis of fragmentation patterns in plasma cell-free DNA (cfDNA) has been shown to distinguish individuals with cancer from healthy controls in multiple case-controlled studies. However, there have been few studies that investigate various types cfDNA fragmentomics patterns in individuals with other diseases. For this purpose, we developed a comprehensive metric, called fragmentation signatures, that integrated the distributions of fragment positioning, fragment length, and fragment end-motifs. Using this metric, we found that individuals with venous thromboembolism, systemic lupus erythematosus, dermatomyositis, or scleroderma had cfDNA fragmentation signatures that closely mimicked those found in individuals with advanced cancers. Furthermore, these signatures were highly correlated with increases in inflammatory markers in the blood. Though these data put substantial limitations on the specificity of fragmentomics-based tests for cancer diagnostics, they also offer ways to improve the interpretability of such tests. Moreover, they should lead to a better understanding of the cells – most likely inflammatory cells - from which plasma cfDNA is derived.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008005","title":"MECOM represses myeloid differentiation through CEBPA downregulation in AML","description":"Transcription factor MECOM, located at 3q26, is essential for hematopoietic stem cells (HSCs) in healthy individuals. Enhancer translocations, due to 3q26 rearrangements, drive out-of-context MECOM expression in an aggressive subtype of leukemia (AML). Aberrantly expressed MECOM is essential for the survival and immature phenotype of these leukemia cells. Direct depletion of MECOM using an endogenous auxin-inducible degron rapidly upregulates expression of myeloid differentiation factor CEBPA. MECOM depletion is also accompanied by a severe loss of CD34 expression and gain of mature myeloid cell surface marker CD15. MECOM exerts its inhibitory effect on differentiation by binding to the +42kb CEBPA enhancer, which is essential for neutrophil development. This is partially dependent on the interaction between MECOM and its essential co-repressor CTBP2, a potential target in this type of AML. We demonstrate that CEBPA overexpression can bypass the MECOM-mediated block of differentiation. In addition, AML patients with MECOM overexpression through enhancer hijacking show significantly reduced CEBPA. Our study provides insight into the mechanism by which MECOM maintains the stem cell state in AML. Furthermore, CEBPA levels are an important read-out for successful targeting of MECOM in 3q26-rearranged AML.","abstract":"Transcription factor MECOM, located at 3q26, is essential for hematopoietic stem cells (HSCs) in healthy individuals. Enhancer translocations, due to 3q26 rearrangements, drive out-of-context MECOM expression in an aggressive subtype of leukemia (AML). Aberrantly expressed MECOM is essential for the survival and immature phenotype of these leukemia cells. Direct depletion of MECOM using an endogenous auxin-inducible degron rapidly upregulates expression of myeloid differentiation factor CEBPA. MECOM depletion is also accompanied by a severe loss of CD34 expression and gain of mature myeloid cell surface marker CD15. MECOM exerts its inhibitory effect on differentiation by binding to the +42kb CEBPA enhancer, which is essential for neutrophil development. This is partially dependent on the interaction between MECOM and its essential co-repressor CTBP2, a potential target in this type of AML. We demonstrate that CEBPA overexpression can bypass the MECOM-mediated block of differentiation. In addition, AML patients with MECOM overexpression through enhancer hijacking show significantly reduced CEBPA. Our study provides insight into the mechanism by which MECOM maintains the stem cell state in AML. Furthermore, CEBPA levels are an important read-out for successful targeting of MECOM in 3q26-rearranged AML.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2024-12-28T08:02:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008006","title":"WENanoSeq_Determining_the_mutation_burden_in_non_invasive_lung_samples","description":"The aim of this study is to investigate the mutational landscape in non-invasive samples from human upper airway. Whole-exome NanoSeq data will be generated using multi-regional biopsies from patients going through head and neck cancer screening.","abstract":"The aim of this study is to investigate the mutational landscape in non-invasive samples from human upper airway. Whole-exome NanoSeq data will be generated using multi-regional biopsies from patients going through head and neck cancer screening.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008007","title":"WENanosSeq___Investigating_the_clonal_dynamics_in_respiratory_tracts_with_cystic_fibrosis","description":"The aim of this project is to better understand the mutational landscape and its interaction with the microbiome in the airways from patients with cystic fibrosis. Whole exome NanoSeq data will be generated by laser captured microdissection (LCM) with fresh frozen bronchus and lung parenchymal tissues.","abstract":"Cystic fibrosis (CF) is a genetic disease leading to significant dysbiosis, particularly in the lungs. One critical cause of poor outcomes in CF patients is chronic lung infections. As a result, this project will be investigating the clonal dynamics and the interactions between mutational patterns and microbial colonisation in CF respiratory tracts using LCM, aiming to better characterise the pathophysiology and stratification of the disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008008","title":"Single_cell_HSC_coloniy_WGS_gene_therapy_trials___Phase2","description":"This study looks at patients undergoing gene therapy for genetic blood  and immune disorders, in particular sickle cell disease. From each patient, single blood HSPC colonies are grown from patient blood at multiple time points: pre gene transduction, post-transduction,  and post-infusion (at several time points).  Whole-genome sequencing will be performed on DNA from these colonies and somatically-acquired mutations will be called. Using these mutations, a phylogeny of these cells can be inferred and further inferences can be made about the gene therapy transduction and engraftment steps.","abstract":"Sickle cell disease (SCD) is an inherited disorder causing considerable morbidity and mortality due to polymerisation of sickle haemoglobin causing deformation of red cells and vaso-occlusion in multiple organs. It is associated with an increased risk of leukemia. Understanding the reasons behind this is particularly important as we move into an era where transplantation and cellular therapies are becoming increasingly utilized. We will be assessing mutational signatures and burdens in normal blood cells, as well as the burden of expanded clones harbouring driver mutations in patients with SCD. We will be comparing these to an age and ethnically matched control cohort (where possible) to better understand how SCD impacts the mutation landscape and clonal dynamics\nof the haematopoietic system.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008009","title":"Genomic_Integrity_and_Safety_of_Stem_cell_Therapy_in_haemoglobinopathies_including_Sickle_Cell_Disease_WGS","description":"This study will involve collecting blood samples from 100 patients with sickle cell disease and 100 matched controls. Granulocytes will be isolated and the DNA extracted. From this, several sequencing approaches will be applied to help better understand the mutational and selective pressures  on blood stem cells in sickle cell disease. We plan to do:\n- Targeted NanoSeq with maximal duplex coverage up to ~4000X (with a custom panel)\n- Standard or low-input WGS to get the germline context that may impact the above\n- If there are insufficient mutation calls from the targeted nanoseq, additional RE-NanoSeq may be applied to better define the mutation burdens and signatures.\nThis part of the study focuses on the whole-genome sequencing.","abstract":"Sickle cell disease (SCD) is an inherited disorder causing considerable morbidity and mortality due to polymerisation of sickle haemoglobin causing deformation of red cells and vaso-occlusion in multiple organs. It is associated with an increased risk of leukemia. Understanding the reasons behind this is particularly important as we move into an era where transplantation and cellular therapies are becoming increasingly utilized. We will be assessing mutational signatures and burdens in normal blood cells, as well as the burden of expanded clones harbouring driver mutations in patients with SCD. We will be comparing these to an age and ethnically matched control cohort (where possible) to better understand how SCD impacts the mutation landscape and clonal dynamics\nof the haematopoietic system.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008010","title":"Gene expression profiling in pregnancy-associated breast cancer","description":"Gene expression profiling by nCounter BC360 panel (Nanostring) gene expression by nCounter BC360 panel (Nanostring) to identify altered pathways and key genes involved in pregnancy-associated breast cancer. Tumor specimens derived from breast cancer patients participating in the following studies sponsored by GEICAM: GEICAM/2012-03, GEICAM/2017-07, and EpiGEICAM.","abstract":"Gene expression profiling by nCounter BC360 panel (Nanostring) gene expression by nCounter BC360 panel (Nanostring) to identify altered pathways and key genes involved in pregnancy-associated breast cancer. Tumor specimens derived from breast cancer patients participating in the following studies sponsored by GEICAM: GEICAM/2012-03, GEICAM/2017-07, and EpiGEICAM.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008011","title":"Preclinical Pediatric Molecular Analysis for Therapy Choice (MATCH)","description":"Purpose:  Pediatric solid tumors arise from diverse tissues during development and exhibit a wide range of molecular, cellular and genetic features. This diversity, combined with the low incidence of pediatric cancer makes it increasingly difficult to personalize therapy for individual patients based on the unique features of their tumors. Therefore, well-credentialed preclinical models that capture the diversity and heterogeneity of pediatric solid tumors are essential for identifying molecular targeted therapeutics for precision medicine. \nExperimental Design:  Here, we report 281 orthotopic patient derived xenografts (O-PDXs) from 224 patients representing 24 different types of pediatric solid tumors. We have performed genomic characterization of the O-PDXs and compared them to their corresponding patient tumors. To demonstrate the feasibility and utility of using such a diverse collection of O-PDXs in preclinical studies, we performed a preclinical pediatric precision medicine trial based on the NCI-COG Pediatric MATCH trial enrollment criteria. We also tested molecular targeted therapy for a novel oncogenic fusion recently reported in pediatric melanoma and precision drug delivery using nano-liposomal irinotecan. \nResults: In the preclinical match study, we identified one specific single agent response to LY3023414 in an osteosarcoma model with a TSC2 variant of unknown significance. Combinations of nano-liposomal irinotecan were effective in treating both Ewing sarcoma and rhabdomyosarcoma xenografts.\nConclusion:  Our studies demonstrate the value of large, well-credentialed preclinical models for future precision medicine in pediatric oncology using single agents, drug combinations and novel drug formulations.","abstract":"Purpose:  Pediatric solid tumors arise from diverse tissues during development and exhibit a wide range of molecular, cellular and genetic features. This diversity, combined with the low incidence of pediatric cancer makes it increasingly difficult to personalize therapy for individual patients based on the unique features of their tumors. Therefore, well-credentialed preclinical models that capture the diversity and heterogeneity of pediatric solid tumors are essential for identifying molecular targeted therapeutics for precision medicine. \nExperimental Design:  Here, we report 281 orthotopic patient derived xenografts (O-PDXs) from 224 patients representing 24 different types of pediatric solid tumors. We have performed genomic characterization of the O-PDXs and compared them to their corresponding patient tumors. To demonstrate the feasibility and utility of using such a diverse collection of O-PDXs in preclinical studies, we performed a preclinical pediatric precision medicine trial based on the NCI-COG Pediatric MATCH trial enrollment criteria. We also tested molecular targeted therapy for a novel oncogenic fusion recently reported in pediatric melanoma and precision drug delivery using nano-liposomal irinotecan. \nResults: In the preclinical match study, we identified one specific single agent response to LY3023414 in an osteosarcoma model with a TSC2 variant of unknown significance. Combinations of nano-liposomal irinotecan were effective in treating both Ewing sarcoma and rhabdomyosarcoma xenografts.\nConclusion:  Our studies demonstrate the value of large, well-credentialed preclinical models for future precision medicine in pediatric oncology using single agents, drug combinations and novel drug formulations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-01-15T15:44:10+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008012","title":"Neuroblastoma_Cambridge_Behjati_WellcomeCore_Bulk_RNA","description":"High-risk neuroblastoma is treated with intensive chemotherapy, and most patients will receive myeloablative therapy followed by an autologous stem cell transplant. Survivors have a 100-fold risk of developing acute myeloid leukaemia within the 10 years that follow relative to the general population. Our study will investigate at high resolution the effects of chemotherapy on the bone marrow for one child with high-risk neuroblastoma. Single cell derived blood colonies from both before and after treatment have been cultured and will be sequenced, allowing us to determine the mutations at the single cell level before and after chemotherapy, and to quantify effects of chemotherapy on the clonal dynamics of the haematopoietic stem cell pool.’ Whole Genome Study.","abstract":"High-risk neuroblastoma is treated with intensive chemotherapy, and most patients will receive myeloablative therapy followed by an autologous stem cell transplant. Survivors have a 100-fold risk of developing acute myeloid leukaemia within the 10 years that follow relative to the general population. Our study will investigate at high resolution the effects of chemotherapy on the bone marrow for one child with high-risk neuroblastoma. Single cell derived blood colonies from both before and after treatment have been cultured and will be sequenced, allowing us to determine the mutations at the single cell level before and after chemotherapy, and to quantify effects of chemotherapy on the clonal dynamics of the haematopoietic stem cell pool.’ Whole Genome Study.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008013","title":"Gene expression profiling in pregnancy-associated breast cancer","description":null,"abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-01-16T13:25:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008014","title":"Comparison of WGBS, EPIC array, EM-seq, and Nanopore sequencing in assessing DNA methylation marks","description":"Bisulfite sequencing has long been the default method for analyzing methylation marks due to its single base resolution. However, the associated DNA degradation poses a concern for fragmented samples. Although several methods have been proposed to circumvent this issue, there has yet to be a clear consensus on which method is best suited for detecting methylation. We present an overview of the two mostly used and two alternative approaches: whole-genome bisulfite sequencing (WGBS), Illumina methylation microarray (EPIC), Enzymatic Methyl-sequencing (EM-seq) and third-generation sequencing by Oxford Nanopore Technologies (ONT). We evaluated DNA methylation levels in three human genomes derived from tissue, cell line, and whole blood.","abstract":"Bisulfite sequencing has long been the default method for analyzing methylation marks due to its single base resolution. However, the associated DNA degradation poses a concern for fragmented samples. Although several methods have been proposed to circumvent this issue, there has yet to be a clear consensus on which method is best suited for detecting methylation. We present an overview of the two mostly used and two alternative approaches: whole-genome bisulfite sequencing (WGBS), Illumina methylation microarray (EPIC), Enzymatic Methyl-sequencing (EM-seq) and third-generation sequencing by Oxford Nanopore Technologies (ONT). We evaluated DNA methylation levels in three human genomes derived from tissue, cell line, and whole blood.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008015","title":"ucfDNA workflows for molecular profiling of malignant disease","description":"Urinary cell-free DNA (ucfDNA) is a promising liquid biopsy analyte obtained by a non-invasive sampling method, particularly valuable in urological cancers due to the proximity of biofluids to the tumor site. However, extremely high fragmentation and low abundance of ucfDNA pose significant analytical challenges. Improper handling and storage can severely affect ucfDNA quality, necessitating optimized pre-analytical workflows for clinical applications. We evaluated multiple pre-analytical workflows, including urine stabilization approaches against unstabilized urine samples. Our results demonstrated that without stabilization, ucfDNA degraded rapidly and minimal quantities remaining after 72 hours. In contrast, urine stabilization preserved ucfDNA integrity, enabling successful downstream analyses, including digital PCR and next-generation sequencing, for mutation detection in cancer-related genes and genome wide copy number profiling. These findings underscore the critical role of stabilization for a reliable ucfDNA analysis and highlight its potential in molecular diagnostics as a complementary tool to plasma-based liquid biopsies.\n ","abstract":"Urinary cell-free DNA (ucfDNA) is a promising liquid biopsy analyte obtained by a non-invasive sampling method, particularly valuable in urological cancers due to the proximity of biofluids to the tumor site. However, extremely high fragmentation and low abundance of ucfDNA pose significant analytical challenges. Improper handling and storage can severely affect ucfDNA quality, necessitating optimized pre-analytical workflows for clinical applications. We evaluated multiple pre-analytical workflows, including urine stabilization approaches against unstabilized urine samples. Our results demonstrated that without stabilization, ucfDNA degraded rapidly and minimal quantities remaining after 72 hours. In contrast, urine stabilization preserved ucfDNA integrity, enabling successful downstream analyses, including digital PCR and next-generation sequencing, for mutation detection in cancer-related genes and genome wide copy number profiling. These findings underscore the critical role of stabilization for a reliable ucfDNA analysis and highlight its potential in molecular diagnostics as a complementary tool to plasma-based liquid biopsies.\n ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008016","title":"Single-cell atlas of > 1.5 million PBMC with multi-layer omics data in Japanese","description":"Osaka Atlas of Immune Cells (OASIS) is multi-omics immune cell atlas from 235 Japanese including COVID-19 patients and healthy subjects. The 5’ single-cell transcriptomics data profiled over 1,500,000 peripheral blood mononuclear cells (PBMCs). OASIS links these single-cell transcriptomics data with host genetics, plasma proteomics, and metagenomics data.","abstract":"Osaka Atlas of Immune Cells (OASIS) is multi-omics immune cell atlas from 235 Japanese including COVID-19 patients and healthy subjects. The 5’ single-cell transcriptomics data profiled over 1,500,000 peripheral blood mononuclear cells (PBMCs). OASIS links these single-cell transcriptomics data with host genetics, plasma proteomics, and metagenomics data.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-01-27T10:25:08+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008017","title":"Vivo_bulk_Behjati_WellcomeCore_RNAseq","description":"Whilst some genomic features of rhabdomyosarcoma are employed in diagnosis and risk stratification in current protocols, new genomic biomarker discovery has been frustrated by small study sample sizes, or necessary focus on a small number of genes/regions of interest. The VIVO biobank currently stores pathological samples from over 600 patients with RMS.  This study has coordinated high quality and detailed clinical annotation of these samples, facilitating the identification of a cohort of clinical outliers and matched controls. These will undergo extensive whole genomic and transcriptomic sequencing to identify novel risk biomarkers and further delineate the genomic landscape of RMS.","abstract":"Whilst some genomic features of rhabdomyosarcoma are employed in diagnosis and risk stratification in current protocols, new genomic biomarker discovery has been frustrated by small study sample sizes, or necessary focus on a small number of genes/regions of interest. The VIVO biobank currently stores pathological samples from over 600 patients with RMS.  This study has coordinated high quality and detailed clinical annotation of these samples, facilitating the identification of a cohort of clinical outliers and matched controls. These will undergo extensive whole genomic and transcriptomic sequencing to identify novel risk biomarkers and further delineate the genomic landscape of RMS.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008018","title":"Leukaemia_Cambridge_Behjati_Wellcome_Core_EMseq","description":"Understanding methylation across paediatric leukaemias.\n\nPaediatric leukaemias are known to be defined by genetic risk categories, that partly determine their clinical outcome. However, patients with apparently “good risk” genetic lesions often relapse, or have resistant disease. To understand why this occurs, we are going to undertake EM-seq of children who have done badly, and those who have done well, alongside whole genome sequencing. For a subset of children, we have also done single-cell RNA sequencing at multiple treatment timepoints, where we plan to link their methylation status, to their gene expression at a single-cell level.","abstract":"Understanding methylation across paediatric leukaemias.\n\nPaediatric leukaemias are known to be defined by genetic risk categories, that partly determine their clinical outcome. However, patients with apparently “good risk” genetic lesions often relapse, or have resistant disease. To understand why this occurs, we are going to undertake EM-seq of children who have done badly, and those who have done well, alongside whole genome sequencing. For a subset of children, we have also done single-cell RNA sequencing at multiple treatment timepoints, where we plan to link their methylation status, to their gene expression at a single-cell level.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-01-29T13:15:23+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008019","title":"VIVO_Behjati_Wellcome_Core_WGS","description":"Whilst some genomic features of rhabdomyosarcoma are employed in diagnosis and risk stratification in current protocols, new genomic biomarker discovery has been frustrated by small study sample sizes, or necessary focus on a small number of genes/regions of interest. The VIVO biobank currently stores pathological samples from over 600 patients with RMS.  This study has coordinated high quality and detailed clinical annotation of these samples, facilitating the identification of a cohort of clinical outliers and matched controls. These will undergo extensive whole genomic and transcriptomic sequencing to identify novel risk biomarkers and further delineate the genomic landscape of RMS.","abstract":"Whilst some genomic features of rhabdomyosarcoma are employed in diagnosis and risk stratification in current protocols, new genomic biomarker discovery has been frustrated by small study sample sizes, or necessary focus on a small number of genes/regions of interest. The VIVO biobank currently stores pathological samples from over 600 patients with RMS.  This study has coordinated high quality and detailed clinical annotation of these samples, facilitating the identification of a cohort of clinical outliers and matched controls. These will undergo extensive whole genomic and transcriptomic sequencing to identify novel risk biomarkers and further delineate the genomic landscape of RMS.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008020","title":"DNAme_heritability_in_solid_tissues__LCM_RNA___NovaSeqX__","description":"Exploring methylation patterns in tissues such as endometrium, colon, stomach, and duodenum. SequenceScape study ID 6891 and relationship with RNAseq. Updated humfres to reflect new AMSBIO humfre. This study is sequenced using the NovaSeqX platform.","abstract":"Exploring methylation patterns in tissues such as endometrium, colon, stomach, and duodenum.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008021","title":"NGS based Aspergillus detection in liquid biopsies of immunocompromised patients","description":null,"abstract":"In immunocompromised pediatric patients, Invasive Pulmonary Aspergillosis (IPA) is a significant threat. While Next-Generation Sequencing (NGS) holds promise in evaluating fungal DNA levels in IPA patients for timely antifungal interventions, standardized NGS-based assessments are lacking. The aim of this study was optimization of the workflow mNGS tailored to Aspergillus detection in liquid biopsy samples. Therefore we applied shotgun Illumina sequencing to liquid biopsy samples, such as Blood plasma or bronchoalveolar lavage (BAL) fluid, with the objective of sequencing intact microbial whole-cell DNA wcDNA or small DNA molecules from degraded microbes (i.e. cell-free DNA, cfDNA). We isolated cfDNA and wcDNA from BAL fluid supernatant and cfDNA from plasma, constructing sequencing libraries using either single-stranded or double-stranded ligation methods. In total, this study encompassed 27 pediatric patients, including 7 diagnosed with probable IPA and 20 external immunocompromised controls (9 plasma samples and 11 BAL fluid supernatants).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-01-30T13:24:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008022","title":"TIRE-seq: an Integrated Sample Extraction and Transcriptomics Workflow for High Throughput Perturbation Studies","description":"TIRE-seq is a novel RNA sequencing method that integrates mRNA purification directly into library preparation, eliminating separate RNA extraction. The technique demonstrated utility across three biological applications, including capturing transcriptional changes in human T cells, identifying genes driving murine dendritic cell differentiation, and analyzing the dose-response effects of temozolomide on patient-derived neurospheres. With its simplified approach and high sequencing efficiency, TIRE-seq offers a cost-effective solution for large-scale gene expression studies.","abstract":"TIRE-seq is a novel RNA sequencing method that integrates mRNA purification directly into library preparation, eliminating separate RNA extraction. The technique demonstrated utility across three biological applications, including capturing transcriptional changes in human T cells, identifying genes driving murine dendritic cell differentiation, and analyzing the dose-response effects of temozolomide on patient-derived neurospheres. With its simplified approach and high sequencing efficiency, TIRE-seq offers a cost-effective solution for large-scale gene expression studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008023","title":"Three-dimensional patient-derived models of glioblastoma retain intra-tumoral heterogeneity","description":"The intra- and inter- tumoral heterogeneity of glioblastoma represents a significant therapeutic challenge, as well as difficulty in generating reliable models for in vitro studies. Here, we quantify the tumor cell composition from matched patient-derived neurospheres (PDN) and organoids (PDO) established from the same primary tumor using a series of multi-omic interrogations, relative to primary tissue","abstract":"The intra- and inter- tumoral heterogeneity of glioblastoma represents a significant therapeutic challenge, as well as difficulty in generating reliable models for in vitro studies. Here, we quantify the tumor cell composition from matched patient-derived neurospheres (PDN) and organoids (PDO) established from the same primary tumor using a series of multi-omic interrogations, relative to primary tissue","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-01-31T01:25:39+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008024","title":"Epigenetic reprogramming mediates monocyte and heterologous T cell-derived cytokine responses after BCG vaccination","description":"Epigenetic reprogramming plays an important role in shaping immune memory traits within both innate (trained immunity) and adaptive immune cells following Bacillus Calmette-Guérin (BCG) vaccination. However, the precise impact of dynamic DNA methylation alterations on immunological responses after BCG vaccination remains inadequately elucidated. To address this knowledge gap, we conducted a comprehensive study by integrating longitudinal analysis and systems biology approaches. We established a cohort of 284 healthy Dutch individuals, capturing data on genetics, cytokine responses to ex vivo stimulation and genome-wide DNA methylation at baseline, as well as at 14 days and 90 days after BCG vaccination. Our findings revealed distinct patterns of DNA methylation alternations in the short- and long-term following BCG vaccination. Moreover, we established that baseline DNA methylation profiles exert influence on the change in interferon-γ (IFN-γ) production upon heterologous (Staphylococcus aureus, S. aureus) stimulation before and after BCG vaccination. Specifically, we identified the regulation of kisspeptin as a novel pathway implicated in the modulation of IFN-γ production, and this finding has been substantiated through experiment validation. We also observed associations between BCG-induced DNA methylation changes and increased IFN-γ and Interleukin-1 β (IL-1β) production upon S. aureus stimulation. Interestingly, by integrating with genetic, epigenetic, and cytokine response data from the same individuals, mediation analysis demonstrates that most of the identified DNA methylation changes play a mediating role between genetic variants and cytokine responses, for example, the changes of cg21375332 near SLC12A3 gene mediated the regulation of genetic variants on IFN-γ changes after BCG vaccination. Sex-specific effects consistently manifested in DNA methylation changes after BCG vaccination and in the association between baseline methylation and cytokine responses. Together, our findings provide deeper insights into immune response mechanisms, crucial for developing effective epigenetic-based medical interventions for personalized medicine.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008025","title":"Genomic_Integrity_and_Safety_of_Stem_cell_Therapy_in_haemoglobinopathies_including_Sickle_Cell_Disease_RENanoSeq","description":"This study will involve collecting blood samples from 100 patients with sickle cell disease and 100 matched controls. Granulocytes will be isolated and the DNA extracted. From this, several sequencing approaches will be applied to help better understand the mutational and selective pressures  on blood stem cells in sickle cell disease. We plan to do:\n- RE Nanoseq i.e. duplex sequencing WGS to get reliable mutation burdens and profiles\n- Targeted NanoSeq with maximal duplex coverage up to ~4000X (with a custom panel, TE-93170215 (SCD v1))\n- Standard or low-input WGS to get the germline context that may impact the above\n- If there are insufficient mutation calls from the targeted nanoseq, additional RE-NanoSeq may be applied to better define the mutation burdens and signatures.\nThis part of the study focuses on the WGS RE-NanoSeq.","abstract":"Sickle cell disease (SCD) is an inherited disorder causing considerable morbidity and mortality due to polymerisation of sickle haemoglobin causing deformation of red cells and vaso-occlusion in multiple organs. It is associated with an increased risk of leukemia. Understanding the reasons behind this is particularly important as we move into an era where transplantation and cellular therapies are becoming increasingly utilized. We will be assessing mutational signatures and burdens in normal blood cells, as well as the burden of expanded clones harbouring driver mutations in patients with SCD. We will be comparing these to an age and ethnically matched control cohort (where possible) to better understand how SCD impacts the mutation landscape and clonal dynamics\nof the haematopoietic system.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008026","title":"Interferon-related inflammaging links epigenetic age acceleration to multimorbidity","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008027","title":"Interferon-related inflammaging links epigenetic age acceleration to multimorbidity","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008028","title":"Interferon-related inflammaging links epigenetic age acceleration to multimorbidity","description":null,"abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008029","title":"Interferon-related inflammaging links epigenetic age acceleration to multimorbidity","description":null,"abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-02-06T06:13:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008030","title":"Interferon-related inflammaging links epigenetic age acceleration to multimorbidity","description":null,"abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-02-06T06:15:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008031","title":"Interferon-related inflammaging links epigenetic age acceleration to multimorbidity","description":null,"abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-02-06T06:16:32+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008032","title":"Genome-wide association study identifies common variants associated with breast cancer in South African Black women","description":"Genome-wide association studies (GWAS) have characterized the contribution of common variants to the development of breast cancer (BC) in populations of European descent, however no GWAS have been reported in resident African populations. This GWAS included 2,485 resident African BC cases and 1,101 population matched controls. Two risk loci were identified, one on chromosome 15, located between UNC13C and RAB27A (rs7181788, p = 1.01x10-08) and a second in an intron of USP22 on chromosome 17 (rs899342, p = 4.62x10-08). RAB27A is a member of the RAS oncogene family associated with invasive growth and metastasis, and UNC13C is involved in tumor progression. The rs899342 SNP is an eQTL for expression of USP22 in a wide range of tissues. Several genome-wide significant signals were detected in a hormone receptor subtype analysis. Comparison of a meta-analysis of other African ancestry BC GWAS datasets predominantly of West African ancestry with our South African data showed limited evidence of shared risk loci, suggesting potential heterogeneity in genetic risk factors for breast cancer in different African populations. A European ancestry derived polygenic risk model for BC was applied to our data, explaining only 0.79% of variance, with an area under the curve of 0.56. This study identified genetic risk factors for BC in a resident African population, but larger studies in this and other African populations are needed to further define the contribution of common variants to BC risk.","abstract":"Genome-wide association studies (GWAS) have characterized the contribution of common variants to the development of breast cancer (BC) in populations of European descent, however no GWAS have been reported in resident African populations. This GWAS included 2,485 resident African BC cases and 1,101 population matched controls. Two risk loci were identified, one on chromosome 15, located between UNC13C and RAB27A (rs7181788, p = 1.01x10-08) and a second in an intron of USP22 on chromosome 17 (rs899342, p = 4.62x10-08). RAB27A is a member of the RAS oncogene family associated with invasive growth and metastasis, and UNC13C is involved in tumor progression. The rs899342 SNP is an eQTL for expression of USP22 in a wide range of tissues. Several genome-wide significant signals were detected in a hormone receptor subtype analysis. Comparison of a meta-analysis of other African ancestry BC GWAS datasets predominantly of West African ancestry with our South African data showed limited evidence of shared risk loci, suggesting potential heterogeneity in genetic risk factors for breast cancer in different African populations. A European ancestry derived polygenic risk model for BC was applied to our data, explaining only 0.79% of variance, with an area under the curve of 0.56. This study identified genetic risk factors for BC in a resident African population, but larger studies in this and other African populations are needed to further define the contribution of common variants to BC risk.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-02-06T07:54:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008033","title":"Molecularly matched targeted therapies plus radiotherapy in patients with newly diagnosed glioblastoma without MGMT promoter hypermethylation (N2M2/NOA-20 phase I/IIa umbrella trial)","description":"Background: Patients with glioblastoma without MGMT promoter hypermethylation are unlikely to benefit from temozolomide (TMZ). Trials aiming at replacing TMZ with targeted agents in not molecularly selected patient populations have failed. \nMethods: This phase I/IIa umbrella trial aimed at showing safety, feasibility, and preliminary efficacy of targeted compounds in addition to standard radiotherapy initiated within 42 days postoperatively. Molecular diagnostics and bioinformatic evaluation are performed within 28 days after surgery. Stratification for treatment takes place in five subtrials, including alectinib, idasanutlin, palbociclib, vismogedib and temsirolimus, according to the best matching molecular alteration. Patients without matching alterations are randomized between subtrials without strong biomarkers using atezolizumab and asunercept and TMZ as standard of care. Primary objective of the phase I parts of the trial was dose finding or dose validation. In the phase IIa trials, centrally determined progression-free survival at six months (PFS-6) is used as endpoint for efficacy with interim analyses for futility (H0: p=0.231). \nResults: From May 2018 through July 2022, 301 patients were enrolled and 228 treated in 13 German NOA sites. The alectinib and vismodegib subtrials were closed since no molecularly matching patients were accrued; the idasanutlin subtrial was closed prior to the optimal dose at nine patients at discretion of the company providing the drug. The TMZ subtrial showed a PFS-6 of 18.52% (10/54 patients) (p=0.831) and a median overall survival (OS) of 12.1 months. Asunercept: PFS-6 of 15.4% (4/26) (p=0.8825) and OS of 12.8 months. Atezolizumab: PFS-6 of 21.4% (9/42) (p=0.660) and OS of 11.7 months. Palbociclib with patients demonstrating CDK4 amplification or CDKN2A/B codeletion: PFS-6 of 24.4% (10/41) (p=0.4823) and OS of 12.6 months. Temsirolimus with patients demonstrating mTOR activation: PFS-6 of 39.1% (18/46) (p=0.0109) and OS of 15.4 months. The regimen-limiting toxicity (RLT)-rate is 34.8%, which is insignificantly above the predefined unacceptable rate for RLTs of 30%. Most RLTs had severity grade 3, one RLT had severity grade 4. No RLTs resulted in death. Conclusions: N2M2 allows for elaborate molecular testing being integrated into the treatment decision and efficient determination of treatment activity for patients with newly diagnosed glioblastoma. There is clinical activity of temsirolimus in patients with tumors harboring an activated mTOR pathway although this is not positively prognostic without mTOR inhibition; there is no clinical activity for asunercept and atezolizumab in not molecularly selected patients and also palbociclib in molecularly selected patients.","abstract":"Background: Patients with glioblastoma without MGMT promoter hypermethylation are unlikely to benefit from temozolomide (TMZ). Trials aiming at replacing TMZ with targeted agents in not molecularly selected patient populations have failed. \nMethods: This phase I/IIa umbrella trial aimed at showing safety, feasibility, and preliminary efficacy of targeted compounds in addition to standard radiotherapy initiated within 42 days postoperatively. Molecular diagnostics and bioinformatic evaluation are performed within 28 days after surgery. Stratification for treatment takes place in five subtrials, including alectinib, idasanutlin, palbociclib, vismogedib and temsirolimus, according to the best matching molecular alteration. Patients without matching alterations are randomized between subtrials without strong biomarkers using atezolizumab and asunercept and TMZ as standard of care. Primary objective of the phase I parts of the trial was dose finding or dose validation. In the phase IIa trials, centrally determined progression-free survival at six months (PFS-6) is used as endpoint for efficacy with interim analyses for futility (H0: p=0.231). \nResults: From May 2018 through July 2022, 301 patients were enrolled and 228 treated in 13 German NOA sites. The alectinib and vismodegib subtrials were closed since no molecularly matching patients were accrued; the idasanutlin subtrial was closed prior to the optimal dose at nine patients at discretion of the company providing the drug. The TMZ subtrial showed a PFS-6 of 18.52% (10/54 patients) (p=0.831) and a median overall survival (OS) of 12.1 months. Asunercept: PFS-6 of 15.4% (4/26) (p=0.8825) and OS of 12.8 months. Atezolizumab: PFS-6 of 21.4% (9/42) (p=0.660) and OS of 11.7 months. Palbociclib with patients demonstrating CDK4 amplification or CDKN2A/B codeletion: PFS-6 of 24.4% (10/41) (p=0.4823) and OS of 12.6 months. Temsirolimus with patients demonstrating mTOR activation: PFS-6 of 39.1% (18/46) (p=0.0109) and OS of 15.4 months. The regimen-limiting toxicity (RLT)-rate is 34.8%, which is insignificantly above the predefined unacceptable rate for RLTs of 30%. Most RLTs had severity grade 3, one RLT had severity grade 4. No RLTs resulted in death. Conclusions: N2M2 allows for elaborate molecular testing being integrated into the treatment decision and efficient determination of treatment activity for patients with newly diagnosed glioblastoma. There is clinical activity of temsirolimus in patients with tumors harboring an activated mTOR pathway although this is not positively prognostic without mTOR inhibition; there is no clinical activity for asunercept and atezolizumab in not molecularly selected patients and also palbociclib in molecularly selected patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-02-10T08:39:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008034","title":"Short-term fasting before living kidney donation has an immune-modulatory effect","description":"Background: Short-Term Fasting (STF) is an intervention reducing the intake of calories, without causing undernutrition or micronutrient-related malnutrition. It aims to systemically improve resilience against acute stress. Several (pre-)clinical studies have suggested protective effects of STF, marking the systemic effects STF can induce in respect to surgery and ischemia-reperfusion injury. In addition, STF also affects the number of circulating immune cells. We aim to determine the effect of STF on the abundance and phenotype of different immune cell populations.\nMethods: Thirty participants were randomly selected from the FAST clinical trial,  including living kidneys donors, randomised to a STF-diet or control arm. In an observational cohort sub-study we prospectively included 30 patients who donated blood samples repeatedly during study runtime. Using flow cytometry analyses, immune cell phenotyping was performed on peripheral blood mononuclear cells. Three panels were designed to investigate the presence and activation status of peripheral T cells, B cells, dendritic cells (DCs) and myeloid cells.\nResults: Eight participants were excluded due to sample constraints. Baseline characteristics showed no significant differences, except for fasting duration. Weight changes were minimal and non-significant across different time intervals, with slight trends towards long-term weight loss pre-surgery. Glucose, insulin, and β-hydroxybutyrate levels differed significantly between groups, reflecting adherence to the fasting diet. Flow cytometry analysis revealed no baseline differences between groups, with high variability within each group. We observed significant changes in immune cell populations due to fasting, particularly in B cells, T cells, and DCs.\nDiscussion: In this study, we found that STF changes the levels and phenotype of immune cells, reducing abundance and activation of T cells and regulatory T cells, increased presence of (naïve) B cells, and elevation of type 1 conventional DCs. Further research should focus on the clinical implications of the changes in immune cell populations and significance of these observed immunological changes.\nBackground: Short-Term Fasting (STF) is an intervention reducing the intake of calories, without causing undernutrition or micronutrient-related malnutrition. It aims to systemically improve resilience against acute stress. Several (pre-)clinical studies have suggested protective effects of STF, marking the systemic effects STF can induce in respect to surgery and ischemia-reperfusion injury. In addition, STF also affects the number of circulating immune cells. We aim to determine the effect of STF on the abundance and phenotype of different immune cell populations.\nMethods: Thirty participants were randomly selected from the FAST clinical trial,  including living kidneys donors, randomised to a STF-diet or control arm. In an observational cohort sub-study we prospectively included 30 patients who donated blood samples repeatedly during study runtime. Using flow cytometry analyses, immune cell phenotyping was performed on peripheral blood mononuclear cells. Three panels were designed to investigate the presence and activation status of peripheral T cells, B cells, dendritic cells (DCs) and myeloid cells.\nResults: Eight participants were excluded due to sample constraints. Baseline characteristics showed no significant differences, except for fasting duration. Weight changes were minimal and non-significant across different time intervals, with slight trends towards long-term weight loss pre-surgery. Glucose, insulin, and β-hydroxybutyrate levels differed significantly between groups, reflecting adherence to the fasting diet. Flow cytometry analysis revealed no baseline differences between groups, with high variability within each group. We observed significant changes in immune cell populations due to fasting, particularly in B cells, T cells, and DCs.\nDiscussion: In this study, we found that STF changes the levels and phenotype of immune cells, reducing abundance and activation of T cells and regulatory T cells, increased presence of (naïve) B cells, and elevation of type 1 conventional DCs. Further research should focus on the clinical implications of the changes in immune cell populations and significance of these observed immunological changes.","abstract":"Background: Short-Term Fasting (STF) is an intervention reducing the intake of calories, without causing undernutrition or micronutrient-related malnutrition. It aims to systemically improve resilience against acute stress. Several (pre-)clinical studies have suggested protective effects of STF, marking the systemic effects STF can induce in respect to surgery and ischemia-reperfusion injury. In addition, STF also affects the number of circulating immune cells. We aim to determine the effect of STF on the abundance and phenotype of different immune cell populations.\nMethods: Thirty participants were randomly selected from the FAST clinical trial,  including living kidneys donors, randomised to a STF-diet or control arm. In an observational cohort sub-study we prospectively included 30 patients who donated blood samples repeatedly during study runtime. Using flow cytometry analyses, immune cell phenotyping was performed on peripheral blood mononuclear cells. Three panels were designed to investigate the presence and activation status of peripheral T cells, B cells, dendritic cells (DCs) and myeloid cells.\nResults: Eight participants were excluded due to sample constraints. Baseline characteristics showed no significant differences, except for fasting duration. Weight changes were minimal and non-significant across different time intervals, with slight trends towards long-term weight loss pre-surgery. Glucose, insulin, and β-hydroxybutyrate levels differed significantly between groups, reflecting adherence to the fasting diet. Flow cytometry analysis revealed no baseline differences between groups, with high variability within each group. We observed significant changes in immune cell populations due to fasting, particularly in B cells, T cells, and DCs.\nDiscussion: In this study, we found that STF changes the levels and phenotype of immune cells, reducing abundance and activation of T cells and regulatory T cells, increased presence of (naïve) B cells, and elevation of type 1 conventional DCs. Further research should focus on the clinical implications of the changes in immune cell populations and significance of these observed immunological changes.\nBackground: Short-Term Fasting (STF) is an intervention reducing the intake of calories, without causing undernutrition or micronutrient-related malnutrition. It aims to systemically improve resilience against acute stress. Several (pre-)clinical studies have suggested protective effects of STF, marking the systemic effects STF can induce in respect to surgery and ischemia-reperfusion injury. In addition, STF also affects the number of circulating immune cells. We aim to determine the effect of STF on the abundance and phenotype of different immune cell populations.\nMethods: Thirty participants were randomly selected from the FAST clinical trial,  including living kidneys donors, randomised to a STF-diet or control arm. In an observational cohort sub-study we prospectively included 30 patients who donated blood samples repeatedly during study runtime. Using flow cytometry analyses, immune cell phenotyping was performed on peripheral blood mononuclear cells. Three panels were designed to investigate the presence and activation status of peripheral T cells, B cells, dendritic cells (DCs) and myeloid cells.\nResults: Eight participants were excluded due to sample constraints. Baseline characteristics showed no significant differences, except for fasting duration. Weight changes were minimal and non-significant across different time intervals, with slight trends towards long-term weight loss pre-surgery. Glucose, insulin, and β-hydroxybutyrate levels differed significantly between groups, reflecting adherence to the fasting diet. Flow cytometry analysis revealed no baseline differences between groups, with high variability within each group. We observed significant changes in immune cell populations due to fasting, particularly in B cells, T cells, and DCs.\nDiscussion: In this study, we found that STF changes the levels and phenotype of immune cells, reducing abundance and activation of T cells and regulatory T cells, increased presence of (naïve) B cells, and elevation of type 1 conventional DCs. Further research should focus on the clinical implications of the changes in immune cell populations and significance of these observed immunological changes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-02-10T10:43:01+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008035","title":"healthy kidney tissue from Wilms tumor patients","description":null,"abstract":"healthy kidney tissue from Wilms tumor patients (of which diagnostics normally sequences tumor), part of the FIURTT clinical study : Hoeijmakers","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008036","title":"HCA_Foetal_Behjati_WellcomeCore_EMseq","description":"An exploratory study of the methylation pattern in foetal tissues, especially liver, which will yield insight into the early epigenetic processes in the developing foetus, as well as serve as normal control data for comparison with paediatric liver tumours.","abstract":"An exploratory study of the methylation pattern in foetal tissues, especially liver, which will yield insight into the early epigenetic processes in the developing foetus, as well as serve as normal control data for comparison with paediatric liver tumours.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008037","title":"DERMATLAS__Rare_cutaneous_tumour_collection_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are all rare skin tumours.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are all rare skin tumours.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008038","title":"DERMATLAS__Rare_cutaneous_tumours_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are all rare skin tumours.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are all rare skin tumours.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008039","title":"Patient-derived tumoroids from CIC::DUX4 rearranged sarcoma identify MCL1 as a therapeutic target","description":"High-risk sarcomas, such as metastasized and relapsed Ewing and CIC-rearranged sarcomas, currently lack effective curative systemic treatment options. Precision medicine approaches offer hope and among them ex vivo drug response profiling of patient-derived tumor cells emerges as a promising novel tool to identify effective drugs for individual patients.\nHere, we established ex vivo culture conditions to propagate Ewing and CIC::DUX4-sarcomas as tumoroids in a co-clinical manner. These models retained their original molecular and functional characteristics, including recurrent ARID1A mutations, and serve as tumor avatars suitable for large-scale drug testing. Indeed, screening a large drug library on a small living biobank of such tumors not only revealed distinct response differences between the two entities, but also identified an exceptional dependency of CIC::DUX4-sarcoma cells on MCL1. Mechanistically. MCL1 was identified as a direct target gene of the CIC::DUX4 fusion protein. Genetic and pharmacological inhibition of MCL1 induced rapid apoptosis in CIC::DUX4-sarcoma cells and inhibited tumor growth in a xenograft model. Thus, MCL1 represents a potential novel therapeutic target for CIC::DUX4-sarcoma.\nOverall, our study highlights the feasibility of co-clinical drug response profiling for individual sarcoma cases and suggests that prospective tests, to evaluate its clinical benefit are highly warranted.","abstract":"High-risk sarcomas, such as metastasized and relapsed Ewing and CIC-rearranged sarcomas, currently lack effective curative systemic treatment options. Precision medicine approaches offer hope and among them ex vivo drug response profiling of patient-derived tumor cells emerges as a promising novel tool to identify effective drugs for individual patients.\nHere, we established ex vivo culture conditions to propagate Ewing and CIC::DUX4-sarcomas as tumoroids in a co-clinical manner. These models retained their original molecular and functional characteristics, including recurrent ARID1A mutations, and serve as tumor avatars suitable for large-scale drug testing. Indeed, screening a large drug library on a small living biobank of such tumors not only revealed distinct response differences between the two entities, but also identified an exceptional dependency of CIC::DUX4-sarcoma cells on MCL1. Mechanistically. MCL1 was identified as a direct target gene of the CIC::DUX4 fusion protein. Genetic and pharmacological inhibition of MCL1 induced rapid apoptosis in CIC::DUX4-sarcoma cells and inhibited tumor growth in a xenograft model. Thus, MCL1 represents a potential novel therapeutic target for CIC::DUX4-sarcoma.\nOverall, our study highlights the feasibility of co-clinical drug response profiling for individual sarcoma cases and suggests that prospective tests, to evaluate its clinical benefit are highly warranted.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-02-17T11:17:15+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008040","title":"The Human Phenotype Project (HPP) is a large-scale deep-phenotype prospective longitudinal and ethnically diverse cohort","description":"The Human Phenotype Project (HPP) is a large-scale deep-phenotype prospective longitudinal and ethnically diverse cohort and biobank that we established. To date, approximately 28,000 participants have enrolled in the study, with over 13,000 having completed their initial visit. The project is aimed at identifying novel molecular signatures with diagnostic, prognostic and therapeutic value, and at developing AI-based predictive models for disease onset and progression. A unique feature of the HPP is its deep and longitudinal profiling that includes medical history, lifestyle and nutritional habits, vital signs, anthropometrics, blood tests, continuous glucose and sleep monitoring, imaging modalities and molecular profiling of the transcriptome, genetics, gut, vaginal and oral microbiome, metabolome and immune system. For several of these modalities, the HPP is the first or largest cohort of its kind. Our analyses of this data provide novel insights into the variation of phenotypes with age and ethnicity, highlighting the importance of having ethnically diverse cohorts and the need for establishing age-dependent norms. We demonstrate how the HPP can be used to unravel personalized molecular signatures of disease by comparison to patient-specific and disease-specific matched healthy controls. Leveraging the extensive dietary and lifestyle HPP data, we systematically identify associations between lifestyle factors and health outcomes. Finally, we present a multi-modal foundation AI model that is trained using self-supervised learning on diet and CGM data and outperforms existing methods in predicting future onset of disease. We extend this AI framework to integrate all data modalities of each subject as a continuous sequence of diverse medical events, creating a digital twin that can simulate interventions and predict health trajectories and outcomes.","abstract":"The Human Phenotype Project (HPP) is a large-scale deep-phenotype prospective longitudinal and ethnically diverse cohort and biobank that we established. To date, approximately 28,000 participants have enrolled in the study, with over 13,000 having completed their initial visit. The project is aimed at identifying novel molecular signatures with diagnostic, prognostic and therapeutic value, and at developing AI-based predictive models for disease onset and progression. A unique feature of the HPP is its deep and longitudinal profiling that includes medical history, lifestyle and nutritional habits, vital signs, anthropometrics, blood tests, continuous glucose and sleep monitoring, imaging modalities and molecular profiling of the transcriptome, genetics, gut, vaginal and oral microbiome, metabolome and immune system. For several of these modalities, the HPP is the first or largest cohort of its kind. Our analyses of this data provide novel insights into the variation of phenotypes with age and ethnicity, highlighting the importance of having ethnically diverse cohorts and the need for establishing age-dependent norms. We demonstrate how the HPP can be used to unravel personalized molecular signatures of disease by comparison to patient-specific and disease-specific matched healthy controls. Leveraging the extensive dietary and lifestyle HPP data, we systematically identify associations between lifestyle factors and health outcomes. Finally, we present a multi-modal foundation AI model that is trained using self-supervised learning on diet and CGM data and outperforms existing methods in predicting future onset of disease. We extend this AI framework to integrate all data modalities of each subject as a continuous sequence of diverse medical events, creating a digital twin that can simulate interventions and predict health trajectories and outcomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-02-18T15:06:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008041","title":"Triple_Neg_ET_WGS_LCMB","description":"Triple Neg ET blood colonies WGS","abstract":"Triple Neg ET blood colonies WGS","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008042","title":"WGS___Panbody_Evaluation_of_Somatic_Mutagenesis_in_LFS","description":"Comparative evaluation of somatic mutagenesis and clonal dynamics across multiple tissue types amongst individuals with inherited cancer predisposition syndromes.","abstract":"WGS of paediatric colonic crypts extracted using laser capture microscopy to identify carcinogens early in life.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008043","title":"CROATIA-Korcula Study","description":null,"abstract":"The CROATIA-Korcula study aims to identify genes influencing risk factors for common diseases such as heart disease, diabetes, glaucoma and stroke.  It examines a family-based, cross-sectional genetics population cohort of adult volunteers recruited in the island of Korčula, Croatia between 2007 and 2014. The genetic research cohort study was established to identify genetic variants, both common and rare, increasing risk of disease. This isolated population has a number of characteristics, the most important being the very large number of distant relatives, which are favourable for the identification of rare variants influencing disease risk. This study describes whole genome sequencing (TruSeq Nano, Illumina) run on a HiSeqX  platform at 30X coverage on 200 individuals best capturing the genetic variation of the entire cohort (N= 2701); they were selected using ANCHAP, an identity by descent inference tool (PMID 23361219).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-02-20T15:41:47+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008044","title":"Whole_Genome_Sequencing_OMELib__LCHPaed_","description":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the Newcastle.","abstract":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the Newcastle.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008045","title":"RNA_Seq_OMELib__LCHPaed_","description":"The transcriptional landscape of haematopoietic cells will be characterized by scRNA-sequencing. Libraries were created using the ResolveOME v1 protocol. Samples have been sourced from the Newcastle","abstract":"The transcriptional landscape of haematopoietic cells will be characterized by scRNA-sequencing. Libraries were created using the ResolveOME v1 protocol. Samples have been sourced from the Newcastle","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008046","title":"Whole_Genome_Sequencing_OMELib__AA_","description":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the Biobank.","abstract":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the Biobank.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008047","title":"RNA_Seq_OMELib__AA_","description":"The transcriptional landscape of haematopoietic cells will be characterized by scRNA-sequencing. Libraries were created using the ResolveOME v1 protocol. Samples have been sourced from the Biobank.","abstract":"The transcriptional landscape of haematopoietic cells will be characterized by scRNA-sequencing. Libraries were created using the ResolveOME v1 protocol. Samples have been sourced from the Biobank","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008048","title":"Leukaemia_Cambridge_Behjati_WellcomeCore_Targeted_Nanoseq_TE_96207414","description":"Targeted nanosequencing of childhood leukaemias\nWe have a large, expanding,  cohort of childhood leukaemias, from Great Ormond Street Hospital, in London, who have undergone scRNA sequencing +/- WGS. To better understand the clonal composition and evolution of these cancers we are planning to use targeted nanosequencing. Over different treatment timepoints we aim to understand which genes are under selection and are the bottlenecks for the development of deadly clones. Alongside this we aim to study mutation in normal tissues, as these children undergo treatment with mutagenic chemotherapy.","abstract":"Targeted nanosequencing of childhood leukaemias\nWe have a large, expanding,  cohort of childhood leukaemias, from Great Ormond Street Hospital, in London, who have undergone scRNA sequencing +/- WGS. To better understand the clonal composition and evolution of these cancers we are planning to use targeted nanosequencing. Over different treatment timepoints we aim to understand which genes are under selection and are the bottlenecks for the development of deadly clones. Alongside this we aim to study mutation in normal tissues, as these children undergo treatment with mutagenic chemotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008049","title":"Somatic mutation profiles in non-tobacco smoking and non-alcohol drinking South African female esophageal squamous cell carcinoma patients of African ancestry","description":"Tumor and normal paired WES data from 15 South African female patients with esophageal squamous cell carcinoma","abstract":"Tumor and normal paired WES data from 15 South African female patients with esophageal squamous cell carcinoma","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008050","title":"Single cell RNA sequencing reveals induced bifurcated differentiation after RUNX1::RUNX1T1 depletion in patient-derived leukemic blasts","description":null,"abstract":"Chromosomal rearrangements that generate novel fusion genes are a hallmark of acute myeloid leukemia (AML). These rearrangements are usually the initiating events of leukemogenesis and maintain their expression throughout the progression to the final leukaemic stage. Due to their exclusive presence in pre-leukemic and leukemic cells, fusion genes represent ideal cancer-specific therapeutic targets. However, most fusion proteins pose significant challenges for conventional drug development. Furthermore, while the functions of fusion proteins have been extensively studied in model systems, their roles in primary patient cells remain poorly understood. In this study, we demonstrate that primary AML cells harboring the chromosomal translocation t(8;21) are critically dependent on the corresponding fusion gene, RUNX1::RUNX1T1, to suppress differentiation and maintain stemness. Silencing RUNX1::RUNX1T1 expression using siRNA-loaded lipid nanoparticles induces significant changes in chromatin accessibility, redirecting the leukemia-associated transcriptional network towards a myeloid differentiation program. Single-cell analyses reveal that this transcriptional reprogramming is associated with the depletion of immature stem and progenitor-like cell populations, accompanied by an expansion of granulocytic and eosinophilic/mast cell-like populations with impaired self-renewal capacity. These findings underscore the essential role of RUNX1::RUNX1T1 in sustaining AML and highlight the therapeutic potential of targeting fusion gene expression in primary AML cells.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-02-24T14:42:25+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008051","title":"A standardised framework for robust fragmentomic feature extraction from cell-free DNA sequencing data","description":"Fragmentomic features of cell-free DNA represent promising non-invasive biomarkers for cancer diagnosis. However, a lack of systematic evaluation of biases in feature quantification has hindered the adoption of such applications. We compared features derived from whole-genome sequencing of ten healthy donors using nine library kits and ten data-processing routes, and validated them in 1,182 plasma samples from published studies. Our results clarify the variations resulting from library preparation and feature quantification methods. We designed the Trim Align Pipeline and the cfDNAPro R package as unified interfaces for data pre-processing, feature extraction, and visualisation, aiming to standardise multimodal feature engineering and integration for machine learning.","abstract":"Fragmentomic features of cell-free DNA represent promising non-invasive biomarkers for cancer diagnosis. However, a lack of systematic evaluation of biases in feature quantification has hindered the adoption of such applications. We compared features derived from whole-genome sequencing of ten healthy donors using nine library kits and ten data-processing routes, and validated them in 1,182 plasma samples from published studies. Our results clarify the variations resulting from library preparation and feature quantification methods. We designed the Trim Align Pipeline and the cfDNAPro R package as unified interfaces for data pre-processing, feature extraction, and visualisation, aiming to standardise multimodal feature engineering and integration for machine learning.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-02-24T15:27:57+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008052","title":"Targeted_NanoSeq___Panbody_Evaluation_of_Somatic_Mutagenesis_in_LFS","description":"Panbody evaluation of somatic driver mutations in individuals with LFS using Targeted NanoSeq","abstract":"Panbody evaluation of somatic driver mutations in individuals with LFS using Targeted NanoSeq","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008053","title":"Discordant_Monozygotic_Twins_ALS (Epigenetics)","description":"We conducted a multi-omics study on a monozygotic twin pair discordant for amyotrophic lateral sclerosis. Here, we submit epigenetic data from EPIC array.","abstract":"We conducted a multi-omics study on a monozygotic twin pair discordant for amyotrophic lateral sclerosis. Here, we submit epigenetic data from EPIC array.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-02-25T11:45:55+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008054","title":"Microarray data of endocrine-resistant and endocrine-sensitive breast cancer patients.","description":"Microarray data of endocrine-resistant and endocrine-sensitive breast cancer patients.","abstract":"Microarray data of endocrine-resistant and endocrine-sensitive breast cancer patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008055","title":"Genomic Landscape and Clonal Architecture in Pediatric Myeloid Neoplasms with Chromosome 7 Deletions","description":"Full and partial loss of chromosome 7 (del7, 7q-) are prevalent cytogenetic abnormalities in pediatric myeloid neoplasms resulting in haploinsufficiency of key hematopoietic regulators on chromosome 7. While the genomic landscape of myeloid neoplasms in adults with del7 and 7q- has been described, pediatric patients with similar chromosome 7  losses have not been compiled into a single, comprehensive study utilizing modern sequencing strategies. To this end, we assembled a cohort of 108 pediatric and young adult patients representing a mixture of diagnoses. Using WGS, WES, and RNAseq, we compared the co-occurring mutations and gene expression levels in our cohort to those found in pediatric and young adult patients with two intact copies of chromosome 7. We also performed single-cell multi-omics on a subset of eight samples.","abstract":"Full and partial loss of chromosome 7 (del7, 7q-) are prevalent cytogenetic abnormalities in pediatric myeloid neoplasms resulting in haploinsufficiency of key hematopoietic regulators on chromosome 7. While the genomic landscape of myeloid neoplasms in adults with del7 and 7q- has been described, pediatric patients with similar chromosome 7  losses have not been compiled into a single, comprehensive study utilizing modern sequencing strategies. To this end, we assembled a cohort of 108 pediatric and young adult patients representing a mixture of diagnoses. Using WGS, WES, and RNAseq, we compared the co-occurring mutations and gene expression levels in our cohort to those found in pediatric and young adult patients with two intact copies of chromosome 7. We also performed single-cell multi-omics on a subset of eight samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-02-26T21:39:44+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008056","title":"Clonal tracing with somatic epimutations reveals dynamics of blood aging","description":"In this study, we generated comprehensive single-cell multi-omic datasets from bone marrow samples collected from 13 donors spanning a wide age range. We applied the scTAMseq protocol to profile DNA methylation and nuclear mutations obtained from 7 total bone marrow aspirates (donors A.1-A.7) and 6 CD34+-enriched bone marrow samples ((donors B.1-B.5 &amp; X.1). Complementary surface marker expression data were acquired by integrating CITE-seq into the scTAMseq workflow (scTAMseq_prot). Targeted RNA sequencing (scTAMARA_rna) was performed alongside scTAMARA_DNA on one CD34+-enriched sample (X.1). Additionally, a dedicated mitochondrial panel (TAMITO_seq) was employed on a peripheral blood sample from a healthy donor (X.2) to assess mitochondrial heterogeneity and facilitate lineage tracing.","abstract":"In this study, we generated comprehensive single-cell multi-omic datasets from bone marrow samples collected from 13 donors spanning a wide age range. We applied the scTAMseq protocol to profile DNA methylation and nuclear mutations obtained from 7 total bone marrow aspirates (donors A.1-A.7) and 6 CD34+-enriched bone marrow samples ((donors B.1-B.5 &amp; X.1). Complementary surface marker expression data were acquired by integrating CITE-seq into the scTAMseq workflow (scTAMseq_prot). Targeted RNA sequencing (scTAMARA_rna) was performed alongside scTAMARA_DNA on one CD34+-enriched sample (X.1). Additionally, a dedicated mitochondrial panel (TAMITO_seq) was employed on a peripheral blood sample from a healthy donor (X.2) to assess mitochondrial heterogeneity and facilitate lineage tracing.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-02-28T11:10:20+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008057","title":"Targeted_NanoSeq__neuroimmune_","description":"Exploring the somatic mutation landscape of neuroimmunology disorders such as demyelination syndromes.","abstract":"Exploring the somatic mutation landscape of neuroimmunology disorders such as demyelination syndromes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008058","title":"Exome_NanoSeq__neuroimmune_","description":"Exploring the somatic mutation landscape of neuroimmunology disorders such as demyelination syndromes.","abstract":"Exploring the somatic mutation landscape of neuroimmunology disorders such as demyelination syndromes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008059","title":"Beyond BRCA deficiency: Clinical and molecular predictors of survival in patients with BRCA-deficient tubo-ovarian high-grade serous carcinoma","description":"Homologous recombination DNA repair deficient (HRD) tumors account for about 50% of tubo-ovarian high-grade serous carcinomas (HGSC) and are associated with a high response to platinum-based chemotherapy. However, a subset of patients with HRD tumors have unexpected resistance to chemotherapy and experience short survival. Our study compared BRCA-deficient and proficient HGSC among patients with short (&lt;3 years, the lowest quartile of overall survival (OS)) versus longer-term (&gt;3 year OS) to identify prognostic markers and potential therapeutic opportunities.  Primary tumors from a cohort of patients with advanced-stage HGSC (n=154) enriched for those with HRD tumors and short survival (n=42) were analyzed using whole-genome sequencing, bulk RNA-sequencing, and DNA methylation profiling. A subset of HRD tumors (n=143) were characterized for immune cell densities by multiplex immunofluorescence. Clinicopathological features were assessed in 1,389 patients with HGSC, including 282 with pathogenic germline BRCA variants (gBRCApv). Findings were validated in two international HGSC cohorts: the Ovarian Tumor Tissue Analysis consortium (n=5,875) and Multisciplinary Ovarian Cancer Outcome Group (n=895).\n\nIn gBRCApv-carriers, residual disease following surgical cytoreduction was not associated with shorter OS unlike in non-carriers where it was strongly associated. While most patients with gBRCApv had a more favorable OS compared to non-carriers, a survival advantage was not apparent in those with variants located outside of BRCA1 exon 10/23 and BRCA2 exon 11/27. Patient survival correlated with HRD score, such that those with a score ≥63 had significantly longer OS compared to those with HRD scores of 42-63 and &lt;42. While higher HRD scores were associated with better survival outcomes, most gBRCApv carriers with a short survival had tumor HRD scores that exceeded the threshold typically considered predictive of a good response to carboplatin or PARP inhibitors. BRCA2-deficient HGSC with loss of the tumor suppressor NF1 was associated with exceptionally favorable outcome (median OS 17 years), whereas amplification of both PIK3CA and RAD21, was associated with poor outcome in BRCA2-deficient HGSC (median OS 2.9 years). The density of tumor-infiltrating CD8+ PD-1+ T cells was prognostic for OS in gBRCApv-carriers.\n\nIn summary, rather than simply the presence or absence of a germline BRCA pathological variant influencing patient survival, the co-occurrence of specific somatic gene alterations, the extent of immune cell infiltration, the level of homologous recombination deficiency, and BRCA-variant location may modify clinical outcomes in patients with BRCA-deficient HGSC. Analysis of exceptional outcome patients, in this case gBRCApv-carriers with an atypically short survival, may identify determinants of outcome applicable to the wider HGSC patient population.","abstract":"Homologous recombination DNA repair deficient (HRD) tumors account for about 50% of tubo-ovarian high-grade serous carcinomas (HGSC) and are associated with a high response to platinum-based chemotherapy. However, a subset of patients with HRD tumors have unexpected resistance to chemotherapy and experience short survival. Our study compared BRCA-deficient and proficient HGSC among patients with short (&lt;3 years, the lowest quartile of overall survival (OS)) versus longer-term (&gt;3 year OS) to identify prognostic markers and potential therapeutic opportunities.  Primary tumors from a cohort of patients with advanced-stage HGSC (n=154) enriched for those with HRD tumors and short survival (n=42) were analyzed using whole-genome sequencing, bulk RNA-sequencing, and DNA methylation profiling. A subset of HRD tumors (n=143) were characterized for immune cell densities by multiplex immunofluorescence. Clinicopathological features were assessed in 1,389 patients with HGSC, including 282 with pathogenic germline BRCA variants (gBRCApv). Findings were validated in two international HGSC cohorts: the Ovarian Tumor Tissue Analysis consortium (n=5,875) and Multisciplinary Ovarian Cancer Outcome Group (n=895).\n\nIn gBRCApv-carriers, residual disease following surgical cytoreduction was not associated with shorter OS unlike in non-carriers where it was strongly associated. While most patients with gBRCApv had a more favorable OS compared to non-carriers, a survival advantage was not apparent in those with variants located outside of BRCA1 exon 10/23 and BRCA2 exon 11/27. Patient survival correlated with HRD score, such that those with a score ≥63 had significantly longer OS compared to those with HRD scores of 42-63 and &lt;42. While higher HRD scores were associated with better survival outcomes, most gBRCApv carriers with a short survival had tumor HRD scores that exceeded the threshold typically considered predictive of a good response to carboplatin or PARP inhibitors. BRCA2-deficient HGSC with loss of the tumor suppressor NF1 was associated with exceptionally favorable outcome (median OS 17 years), whereas amplification of both PIK3CA and RAD21, was associated with poor outcome in BRCA2-deficient HGSC (median OS 2.9 years). The density of tumor-infiltrating CD8+ PD-1+ T cells was prognostic for OS in gBRCApv-carriers.\n\nIn summary, rather than simply the presence or absence of a germline BRCA pathological variant influencing patient survival, the co-occurrence of specific somatic gene alterations, the extent of immune cell infiltration, the level of homologous recombination deficiency, and BRCA-variant location may modify clinical outcomes in patients with BRCA-deficient HGSC. Analysis of exceptional outcome patients, in this case gBRCApv-carriers with an atypically short survival, may identify determinants of outcome applicable to the wider HGSC patient population.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-03-03T21:44:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008060","title":"Genetic origins of the Kiritimati population from central-eastern Micronesia","description":"The migration of Austronesian-speaking populations through Oceania has intrigued researchers for decades. The Kiribati islands, situated along the boundaries of Micronesia and Polynesia, provide a crucial link in this migration. We analyzed the genome-wide data of the Kiritimati population of Kiribati to uncover their genetic origins and connections with other Oceanian groups. Our study reveals that the Kiritimati population primarily exhibits Remote Oceanian-related ancestry associated with ancient Lapita and present-day Polynesian populations. In addition, our identity-by-descent analysis identifies populations from Philippines as their closest relatives in Island Southeast Asia. The genetic links between Kiritimati, ancient Lapita, and modern Polynesians underscore the shared ancestry and continuous gene flow across these regions. This genetic continuity and ongoing links are supported by linguistic and cultural evidence, illustrating a complex history of migration and admixture in Oceania.","abstract":"The migration of Austronesian-speaking populations through Oceania has intrigued researchers for decades. The Kiribati islands, situated along the boundaries of Micronesia and Polynesia, provide a crucial link in this migration. We analyzed the genome-wide data of the Kiritimati population of Kiribati to uncover their genetic origins and connections with other Oceanian groups. Our study reveals that the Kiritimati population primarily exhibits Remote Oceanian-related ancestry associated with ancient Lapita and present-day Polynesian populations. In addition, our identity-by-descent analysis identifies populations from Philippines as their closest relatives in Island Southeast Asia. The genetic links between Kiritimati, ancient Lapita, and modern Polynesians underscore the shared ancestry and continuous gene flow across these regions. This genetic continuity and ongoing links are supported by linguistic and cultural evidence, illustrating a complex history of migration and admixture in Oceania.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-03-04T13:35:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008061","title":"Nf1_Cambridge_Behjati_Wellcome_Core_Sc_Rna","description":"We have shown that histologically normal tissues from patients with neurofibromatosis exhibit frequent second hits that inactivate the wild-type NF1 allele (work under review). Inactivation of both copies of NF1, therefore, is not sufficient to transform a tissue to malignancy. Previous studies, however, have found the inactivation of both copies of NF1 to be the only discernible driver events in certain low grade tumours. This raises the question, therefore, as to why two hits sometimes transform a cell to a low grade tumour and sometimes do not. We hope to resolve this through a multiomic study that compares histologically normal cells with two NF1 hits with tumours with two NF1 hits.","abstract":"We have shown that histologically normal tissues from patients with neurofibromatosis exhibit frequent second hits that inactivate the wild-type NF1 allele (work under review). Inactivation of both copies of NF1, therefore, is not sufficient to transform a tissue to malignancy. Previous studies, however, have found the inactivation of both copies of NF1 to be the only discernible driver events in certain low grade tumours. This raises the question, therefore, as to why two hits sometimes transform a cell to a low grade tumour and sometimes do not. We hope to resolve this through a multiomic study that compares histologically normal cells with two NF1 hits with tumours with two NF1 hits.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008062","title":"Single-cell RNA-sequencing of a multi-region pleural mesothelioma case","description":"Single-cell RNA-sequencing from three distant regions of an epithelioid pleural mesothelioma case.","abstract":"Single-cell RNA-sequencing from three distant regions of an epithelioid pleural mesothelioma case.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-03-04T19:39:38+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008063","title":"Limited Association between HRR Gene Alterations and HRD in Molecular Tumor Board Cancer Samples: Who should be tested for HRD?","description":"Alterations in Homologous Recombination Repair (HRR) Pathway genes have been found to be associated with HR-Deficiency (HRD), which is an approved biomarker for PARP Inhibitor (PARPi) treatment. The aim of a Molecular Tumor Board (MTB) is to identify molecular alterations in cancer patients with advanced tumors that may suggest off-label treatment options. So far, few studies have analyzed the presence of HRR gene mutations and their association with HRD outside of clinical studies. Currently, no data on HRD testing in the setting of a MTB have been published. For the present study, a cohort of 237 patients encompassing 24 different tumor entities was collected from the MTB of the Comprehensive Cancer Center Erlangen-EMN. \nWe show that an elevated Genomic Instability Score (GIS ≥ 42) can occur in samples with and without mutations in HRR-related genes. Overall, 38.1% of cancer samples with BRCA1/2 mutations, 10.9% of tumors with alterations in HRR genes other than BRCA1/2, and 4.3% of cancer samples without HRR gene mutations harbored an elevated GIS. Notably, our data show that various inactivating BRCA1/2 mutations are not associated with an elevated GIS.\nTaken together, panCancer assessment of HRD in addition to BRCA1/2 and other HRR gene mutational analysis is recommended to guide decisions regarding PARPi treatment. Further studies are needed to establish thresholds for GIS in non-ovarian cancer entities. Finally, HRD can be observed in 4.3% of BRCA1/2 and other HRR gene wildtype cancer samples, and may emerge as an independent biomarker for PARPi in the future.","abstract":"Alterations in Homologous Recombination Repair (HRR) Pathway genes have been found to be associated with HR-Deficiency (HRD), which is an approved biomarker for PARP Inhibitor (PARPi) treatment. The aim of a Molecular Tumor Board (MTB) is to identify molecular alterations in cancer patients with advanced tumors that may suggest off-label treatment options. So far, few studies have analyzed the presence of HRR gene mutations and their association with HRD outside of clinical studies. Currently, no data on HRD testing in the setting of a MTB have been published. For the present study, a cohort of 237 patients encompassing 24 different tumor entities was collected from the MTB of the Comprehensive Cancer Center Erlangen-EMN. \nWe show that an elevated Genomic Instability Score (GIS ≥ 42) can occur in samples with and without mutations in HRR-related genes. Overall, 38.1% of cancer samples with BRCA1/2 mutations, 10.9% of tumors with alterations in HRR genes other than BRCA1/2, and 4.3% of cancer samples without HRR gene mutations harbored an elevated GIS. Notably, our data show that various inactivating BRCA1/2 mutations are not associated with an elevated GIS.\nTaken together, panCancer assessment of HRD in addition to BRCA1/2 and other HRR gene mutational analysis is recommended to guide decisions regarding PARPi treatment. Further studies are needed to establish thresholds for GIS in non-ovarian cancer entities. Finally, HRD can be observed in 4.3% of BRCA1/2 and other HRR gene wildtype cancer samples, and may emerge as an independent biomarker for PARPi in the future.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-03-05T13:51:43+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008064","title":"Delineation of the heterogeneous molecular landscape of HRS cells and their biological contributions to forming comprehensive TME ecosystems.","description":"The tissue architecture of classic Hodgkin Lymphoma (CHL) is unique among cancers and characterized by rare malignant Hodgkin and Reed-Sternberg cells that are co-evolving in a complex ecosystem of immune cells in the tumor microenvironment. The lack of a comprehensive systems-level interrogation has hindered the description of disease heterogeneity and clinically relevant molecular subtypes. Here, we employed an integrative, multimodal approach to characterize CHL tumors using malignant cell sequencing, spatial transcriptomics and imaging mass cytometry. We identified four molecular subtypes (CST, CN913, STB, and CN2P) each characterized by distinct clinical features, mutational patterns, malignant cell gene expression profiles, and spatial architecture of immune cell populations. Functional modeling of CSF2RB mutations, a characteristic feature of CST, revealed dysregulated oncogenic signaling and changes in tumor microenvironment crosstalk. These findings highlight the significance of multi-dimensional profiling in elucidating patterns of molecular alterations that drive immune ecosystems and underlie therapeutically exploitable vulnerabilities.","abstract":"The tissue architecture of classic Hodgkin Lymphoma (CHL) is unique among cancers and characterized by rare malignant Hodgkin and Reed-Sternberg cells that are co-evolving in a complex ecosystem of immune cells in the tumor microenvironment. The lack of a comprehensive systems-level interrogation has hindered the description of disease heterogeneity and clinically relevant molecular subtypes. Here, we employed an integrative, multimodal approach to characterize CHL tumors using malignant cell sequencing, spatial transcriptomics and imaging mass cytometry. We identified four molecular subtypes (CST, CN913, STB, and CN2P) each characterized by distinct clinical features, mutational patterns, malignant cell gene expression profiles, and spatial architecture of immune cell populations. Functional modeling of CSF2RB mutations, a characteristic feature of CST, revealed dysregulated oncogenic signaling and changes in tumor microenvironment crosstalk. These findings highlight the significance of multi-dimensional profiling in elucidating patterns of molecular alterations that drive immune ecosystems and underlie therapeutically exploitable vulnerabilities.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-01-27T16:06:32.538318+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008065","title":"Human_NK_exhaustion_RNAseq","description":"Human peripheral blood Natural Killer cells have been expanded in culture and treated in particular ways to induce exhaustion. This aims to provide a complete characterisation of these treatments at the transcriptome level.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Human peripheral blood Natural Killer cells have been expanded in culture and treated in particular ways to induce exhaustion. This aims to provide a complete characterisation of these treatments at the transcriptome level.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008066","title":"Human_CD8_T_exhaustion_RNAseq","description":"Human peripheral blood CD8 T cells have been expanded with multiple rounds of stimulation to induce exhaustion. This aims to provide a complete characterisation of these temporal changes at the transcriptome level.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Human peripheral blood CD8 T cells have been expanded with multiple rounds of stimulation to induce exhaustion. This aims to provide a complete characterisation of these temporal changes at the transcriptome level.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008067","title":"Sequencing of patient tissue and patient derived organoids in colon cancer","description":"Multiome (ATAC + RNA) sequencing of cancerous primary tissue and cancer organoids derived from the same patient. Nanopore and whole exome sequencing of selected samples.","abstract":"Multiome (ATAC + RNA) sequencing of cancerous primary tissue and cancer organoids derived from the same patient. Nanopore and whole exome sequencing of selected samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-03-13T13:30:27+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008068","title":"Detection of cancers three years prior to diagnosis using plasma cell-free DNA","description":"A major goal of early cancer detection is to identify subclinical disease when the tumor burden is low, so that treatments are more effective. But how early can cancers be detected prior to clinical signs or symptoms? This question can be answered only through the evaluation of participants whose clinical course has not been altered by the study itself. We here describe such an evaluation, performed on prospectively collected plasma samples from the Atherosclerosis Risk in Communities (ARIC) study, including 26 participants diagnosed with cancer and 26 matched controls. At the index time point, eight of these 52 participants scored positively with a multicancer early detection (MCED) blood test. All eight of these participants were diagnosed with cancer within 4 months after blood collection. In six of these 8 participants, we were able to assess an earlier plasma sample collected 3.1 to 3.5 years prior to clinical diagnosis. In four of these six participants, the same mutations detected by the MCED test could be identified, but at 8.6 to 79-fold lower levels. These results demonstrate that it is possible to detect circulating tumor DNA (ctDNA) more than three years prior to clinical diagnosis, and provide benchmark sensitivities required for the success of ctDNA-based tests for this purpose.","abstract":"A major goal of early cancer detection is to identify subclinical disease when the tumor burden is low, so that treatments are more effective. But how early can cancers be detected prior to clinical signs or symptoms? This question can be answered only through the evaluation of participants whose clinical course has not been altered by the study itself. We here describe such an evaluation, performed on prospectively collected plasma samples from the Atherosclerosis Risk in Communities (ARIC) study, including 26 participants diagnosed with cancer and 26 matched controls. At the index time point, eight of these 52 participants scored positively with a multicancer early detection (MCED) blood test. All eight of these participants were diagnosed with cancer within 4 months after blood collection. In six of these 8 participants, we were able to assess an earlier plasma sample collected 3.1 to 3.5 years prior to clinical diagnosis. In four of these six participants, the same mutations detected by the MCED test could be identified, but at 8.6 to 79-fold lower levels. These results demonstrate that it is possible to detect circulating tumor DNA (ctDNA) more than three years prior to clinical diagnosis, and provide benchmark sensitivities required for the success of ctDNA-based tests for this purpose.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-03-13T16:21:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008069","title":"Epi2Diag","description":" Genomic DNA was extracted from whole blood\n      and bisulfite converted using the EZ DNA Methylation Lightning\n      Kit (Zymo research). DNA methylation profile was then derived\n      using Illumina’s Infinium EPIC array v2.0. in accordance with\n      the manufacturer’s protocol at the ASGARD-Rouen genomic\n      platform (Inserm U1245, University of Rouen and Rouen University Hospital, Rouen France) on an Illumina NextSeq550 scanner. ","abstract":"Raw methylation array data (Illumina EPIC v2.0. arrays) of patients with rare neurodevelopmental disorders (Idat files) obtained from DNA isolated from whole blood in the purpose of investigating new episignatures and providing independent validation datasets for existing episignatures.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008070","title":"Epi2Diag","description":" Genomic DNA was extracted from whole blood\n      and bisulfite converted using the EZ DNA Methylation Lightning\n      Kit (Zymo research). DNA methylation profile was then derived\n      using Illumina’s Infinium EPIC array v2.0. in accordance with\n      the manufacturer’s protocol at the ASGARD-Rouen genomic\n      platform (Inserm U1245, University of Rouen and Rouen University Hospital, Rouen France) on an Illumina NextSeq550 scanner. ","abstract":"Raw methylation array data (Illumina EPIC v2.0. arrays) of patients with rare neurodevelopmental disorders (Idat files) obtained from DNA isolated from whole blood in the purpose of investigating new episignatures and providing independent validation datasets for existing episignatures.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-03-15T11:57:21+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008071","title":"RRBS data from TRACERx non-small cell lung cancer (NSCLC) tumours and matched normal adjacent tissue.","description":"TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC).","abstract":"TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-03-17T08:51:52+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008072","title":"Atypical tetrasomy 18 in a hepatoblastoma patient","description":"Constitutive aneuploidy often underlies developmental defects, while copy-number alterations are recurrent somatic events in cancers. Rarely, mosaic aneuploidy links developmental defects and cancer development, yet its molecular basis remains elusive.\nWe report the first cancer case in a tetrasomy 18 patient—a female who developed hepatoblastoma at age two and remains recurrence-free 24 months post-surgery and chemotherapy. Whole-genome sequencing and Fluorescent in situ hybridization (FISH) uncovered a complex rearrangement with eight breakpoints between 18p11.32 to 18q12.1, present in 10% of liver and blood cells. Haplotype analysis revealed a pre-zygotic origin, with mosaicism arising from early rescue by loss of the rearranged chromosome. Strikingly, all tumor cells retained this rearranged chromosome. Single-nucleus RNA-seq of liver and hepatoblastoma tissue traced the aneuploidy’s evolution during gametogenesis, organogenesis, and tumorigenesis. This study provides insights into mechanisms of aneuploidy-driven cancer, highlighting the interplay of mosaicism, developmental defects, and tumor evolution in a rare genetic syndrome.","abstract":"Constitutive aneuploidy often underlies developmental defects, while copy-number alterations are recurrent somatic events in cancers. Rarely, mosaic aneuploidy links developmental defects and cancer development, yet its molecular basis remains elusive.\nWe report the first cancer case in a tetrasomy 18 patient—a female who developed hepatoblastoma at age two and remains recurrence-free 24 months post-surgery and chemotherapy. Whole-genome sequencing and Fluorescent in situ hybridization (FISH) uncovered a complex rearrangement with eight breakpoints between 18p11.32 to 18q12.1, present in 10% of liver and blood cells. Haplotype analysis revealed a pre-zygotic origin, with mosaicism arising from early rescue by loss of the rearranged chromosome. Strikingly, all tumor cells retained this rearranged chromosome. Single-nucleus RNA-seq of liver and hepatoblastoma tissue traced the aneuploidy’s evolution during gametogenesis, organogenesis, and tumorigenesis. This study provides insights into mechanisms of aneuploidy-driven cancer, highlighting the interplay of mosaicism, developmental defects, and tumor evolution in a rare genetic syndrome.","study_type":"Other","pubmed_ids":[42019868],"external_links":null,"is_released":true,"released_date":"2025-03-17T11:15:31+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008073","title":"The G2 gene expression signature and MYC overexpression are independent poor prognostic factors in childhood high-grade osteosarcoma","description":"Purpose\nIn high-grade osteosarcoma, prognostic factors at diagnosis are insufficient for stratifying patients into relevant subgroups. Recently, a transcriptomic study developed the G1/G2 gene expression signature, in which the G2 signature was associated with unfavorable survival. An orthogonal study identified MYC amplification as an unfavorable prognostic factor using targeted next-generation sequencing. The purpose of this study was to validate the independent prognostic value and to investigate the combined prognostic value of the G1/G2 signature with, MYC amplification and/or MYC expression for survival prediction. \nMaterial and methods\nThis study included pediatric and adolescent patients with high-grade osteosarcoma. RNA sequencing was performed in 48 patients. Whole-exome sequencing was performed in 40 patients. Gene expression signature scores, MYC amplification (defined as &gt; 7 copies) and MYC expression levels were calculated. Multivariable Cox proportional hazards analysis was performed for event-free survival (EFS) (primary endpoint) and overall survival (OS) (secondary endpoint). \nResults\nIn the full cohort, the 3-year event-free survival rate was 37%. In multivariable Cox regression analysis with metastatic disease stage (n=21, 44%) as covariate, the G2 signature and MYC expression were independently associated with worse outcomes in terms of EFS (Hazard ratio (HR) 3.32, 95% confidence interval (CI) 1.34-8.21 and HR 3.38, 95%-CI 1.71-6.66, respectively) and OS (HR 4.07, 95%-CI 1.19-13.9 and HR 2.88, 95%-CI 1.22-6.76, respectively). MYC amplification was not associated with EFS or OS in univariable analysis (HR 1.88, 95% -CI 0.74-4.77 and HR 0.79, 95%-CI 0.21-3.05, respectively). \nConclusion \nThe G2 gene expression signature and MYC expression were independently associated with unfavorable outcomes in a pediatric cohort of patients with high-grade osteosarcoma. The combined prognostic value warrants further prospective validation and could potentially serve as a stratification marker for future osteosarcoma treatment protocols.","abstract":"Purpose\nIn high-grade osteosarcoma, prognostic factors at diagnosis are insufficient for stratifying patients into relevant subgroups. Recently, a transcriptomic study developed the G1/G2 gene expression signature, in which the G2 signature was associated with unfavorable survival. An orthogonal study identified MYC amplification as an unfavorable prognostic factor using targeted next-generation sequencing. The purpose of this study was to validate the independent prognostic value and to investigate the combined prognostic value of the G1/G2 signature with, MYC amplification and/or MYC expression for survival prediction. \nMaterial and methods\nThis study included pediatric and adolescent patients with high-grade osteosarcoma. RNA sequencing was performed in 48 patients. Whole-exome sequencing was performed in 40 patients. Gene expression signature scores, MYC amplification (defined as &gt; 7 copies) and MYC expression levels were calculated. Multivariable Cox proportional hazards analysis was performed for event-free survival (EFS) (primary endpoint) and overall survival (OS) (secondary endpoint). \nResults\nIn the full cohort, the 3-year event-free survival rate was 37%. In multivariable Cox regression analysis with metastatic disease stage (n=21, 44%) as covariate, the G2 signature and MYC expression were independently associated with worse outcomes in terms of EFS (Hazard ratio (HR) 3.32, 95% confidence interval (CI) 1.34-8.21 and HR 3.38, 95%-CI 1.71-6.66, respectively) and OS (HR 4.07, 95%-CI 1.19-13.9 and HR 2.88, 95%-CI 1.22-6.76, respectively). MYC amplification was not associated with EFS or OS in univariable analysis (HR 1.88, 95% -CI 0.74-4.77 and HR 0.79, 95%-CI 0.21-3.05, respectively). \nConclusion \nThe G2 gene expression signature and MYC expression were independently associated with unfavorable outcomes in a pediatric cohort of patients with high-grade osteosarcoma. The combined prognostic value warrants further prospective validation and could potentially serve as a stratification marker for future osteosarcoma treatment protocols.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-03-17T12:49:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008074","title":"Nucleotide insufficiency induced by p53 deficiency leads to replication stress driving genomic instability.","description":"P53 plays a critical role in preventing DNA damage accumulation by activating repair processes, inducing cell cycle arrest, or triggering apoptosis. Loss of p53 leads to replication stress and genomic instability, yet the mechanisms underlying these effects and their contribution to catastrophic events like chromothripsis remain poorly understood. Using patient-derived fibroblasts with germline p53 variants that spontaneously undergo chromothripsis, as well as p53-downregulated fibroblasts, we discovered that p53 loss disrupts the balance between nucleotide consumption and production by increasing transcription and decreasing nucleotide biosynthesis, respectively. This imbalance results in insufficient nucleotide pools, leading to replication stress. We further demonstrated that this replication stress triggers telomere dysfunction and micronuclei formation, ultimately causing chromothripsis. Supplementing nucleosides or inhibiting transcription rescued replication stress and genomic instability. We also observed the emergence of dominant chromothriptic clones, which exhibited normal DNA replication, telomere stabilization, and extrachromosomal circular DNA structures, highlighting critical features for clonal selection and expansion.","abstract":"P53 plays a critical role in preventing DNA damage accumulation by activating repair processes, inducing cell cycle arrest, or triggering apoptosis. Loss of p53 leads to replication stress and genomic instability, yet the mechanisms underlying these effects and their contribution to catastrophic events like chromothripsis remain poorly understood. Using patient-derived fibroblasts with germline p53 variants that spontaneously undergo chromothripsis, as well as p53-downregulated fibroblasts, we discovered that p53 loss disrupts the balance between nucleotide consumption and production by increasing transcription and decreasing nucleotide biosynthesis, respectively. This imbalance results in insufficient nucleotide pools, leading to replication stress. We further demonstrated that this replication stress triggers telomere dysfunction and micronuclei formation, ultimately causing chromothripsis. Supplementing nucleosides or inhibiting transcription rescued replication stress and genomic instability. We also observed the emergence of dominant chromothriptic clones, which exhibited normal DNA replication, telomere stabilization, and extrachromosomal circular DNA structures, highlighting critical features for clonal selection and expansion.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-03-19T08:20:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008075","title":"Profiling_vaccine_mediated_and_natural_immunity_to_Vibrio_cholerae_through_sequencing_approaches_during_the_2024_cholera_outbreak_Zambia_trans","description":"Gene expression of PBMCs collected from vaccinated and convalescent cholera patients in Zambia. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Cholera is a disease of significant global health burden and is characterised by acute watery diarrhoea and severe dehydration. In Zambia, the 2023 - 2024 cholera outbreak resulted in approximately 20,000 cases and 700 deaths. The oral cholera vaccine, Shanchol™, was used to aid outbreak control, but the majority of patients received one instead of the recommended two doses due to supply shortages. While the difference in natural and vaccine-mediated immunity to cholera in Zambia has been previously explored through serological assays, here we describe the heterogeneity in gene expression of peripheral blood mononuclear cells collected from vaccinated and convalescent cholera patients in Zambia. The immune response inferred from this transcriptomic sequencing was also correlated with the gut microbiome composition of these individuals. These approaches allow us to describe the role of cellular immunity in long-term protection against cholera.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008076","title":"Zambia_Oesophagus_section_sequencing","description":"We wish to understand changes in the DNA and transcriptome of the oesophageal epithelium in areas of high ESCC incidence","abstract":"We wish to understand changes in the DNA and transcriptome of the oesophageal epithelium in areas of high ESCC incidence","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008077","title":"Low_input_RNA_seq_oesophagus_Zambia","description":"We wish to understand changes in the transcriptome of the oesophageal epithelium in areas of high ESCC incidence","abstract":"We wish to understand changes in the transcriptome of the oesophageal epithelium in areas of high ESCC incidence","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008078","title":"Aplastic_Anaemia_Bulk_LCMB_WGS","description":"The mutational landscape of haematopoietic cells will be characterized by LCMB-WGS. Samples have been sourced from Cambridge Blood and Stem Cell Biobank (CBSB).","abstract":"The mutational landscape of haematopoietic cells will be characterized by LCMB-WGS. Samples have been sourced from Cambridge Blood and Stem Cell Biobank (CBSB).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008079","title":"Diagnostic Exome Sequencing","description":null,"abstract":"Diagnostic Exome Sequencing","study_type":"Exome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008080","title":"Optical genome mapping was performed for 85 samples with large repeat expansions in RFC1, DMPK, or CNBP. Subsequently we determined exact repeat sizes and repeat stability.","description":"Short tandem repeats (STRs) are common variations in human genomes that frequently expand or contract, causing genetic disorders, mainly when expanded. Traditional diagnostic methods for identifying these expansions, such as repeat-primed PCR and Southern blotting, are often labor-intensive, locus-specific, and are unable to precisely determine long repeat expansions. Sequencing-based methods, though capable of genome-wide detection, are limited by inaccuracy (short-read technologies) and high associated costs (long-read technologies).\n\nThis study evaluated optical genome mapping (OGM) as an efficient, accurate approach for measuring STR lengths and assessing somatic stability in 85 samples with known pathogenic repeat expansions in DMPK, CNBP, and RFC1, causing myotonic dystrophy types 1 and 2 and cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), respectively. Three workflows—manual de novo assembly, local guided assembly (local-GA), and a molecule distance script—were applied, of which the latter two were developed as part of this study to assess the repeat sizes and somatic repeat stability.\n\nOGM successfully identified 84/85 (98.8%) of the pathogenic expansions, distinguishing between wild-type and expanded alleles or between two expanded alleles in recessive cases, with greater accuracy than standard of care (SOC) for long repeats and no apparent upper size limit. Notably, OGM detected somatic instability in a subset of DMPK, CNBP, and RFC1 samples. These findings suggest OGM could advance diagnostic accuracy for large repeat expansions, providing a more comprehensive genome-wide assay for repeat expansion disorders by measuring exact repeat lengths and somatic instability across multiple loci simultaneously.\n","abstract":"Short tandem repeats (STRs) are common variations in human genomes that frequently expand or contract, causing genetic disorders, mainly when expanded. Traditional diagnostic methods for identifying these expansions, such as repeat-primed PCR and Southern blotting, are often labor-intensive, locus-specific, and are unable to precisely determine long repeat expansions. Sequencing-based methods, though capable of genome-wide detection, are limited by inaccuracy (short-read technologies) and high associated costs (long-read technologies).\n\nThis study evaluated optical genome mapping (OGM) as an efficient, accurate approach for measuring STR lengths and assessing somatic stability in 85 samples with known pathogenic repeat expansions in DMPK, CNBP, and RFC1, causing myotonic dystrophy types 1 and 2 and cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), respectively. Three workflows—manual de novo assembly, local guided assembly (local-GA), and a molecule distance script—were applied, of which the latter two were developed as part of this study to assess the repeat sizes and somatic repeat stability.\n\nOGM successfully identified 84/85 (98.8%) of the pathogenic expansions, distinguishing between wild-type and expanded alleles or between two expanded alleles in recessive cases, with greater accuracy than standard of care (SOC) for long repeats and no apparent upper size limit. Notably, OGM detected somatic instability in a subset of DMPK, CNBP, and RFC1 samples. These findings suggest OGM could advance diagnostic accuracy for large repeat expansions, providing a more comprehensive genome-wide assay for repeat expansion disorders by measuring exact repeat lengths and somatic instability across multiple loci simultaneously.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008081","title":"Profiling_the_Microbiome_of_Early_Life_Gut_Samples","description":"The human gut microbiome (GM), defined as the microorganisms that reside in the human gastrointestinal tract, has been identified as critical for normal intestinal development and physiology. However, to-date, the majority of studies characterizing the gut microbiome has relied on stool samples, thereby limiting insights into the regionality of the gut and how its microbiota differs along its length. As a result, this project seeks to profile the adjacent microbiota of various regions along the intestinal tract from pediatric intestinal tissue and their associated mucosal washes, enabling insights into tissue-specific microbiomes. Due to the expected low microbial biomass of these samples, donor stool (when available) will also be metagenomically profiled as positive controls, which will enable us to benchmark our low-biomass processing methods with existing protocols. By sampling pediatric patients of diverse ages and health statuses, this metagenomic data will also be valuable for understanding the gut microbiome of the developing human gut across time and space. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"The human gut microbiome (GM), defined as the microorganisms that reside in the human gastrointestinal tract, has been identified as critical for normal intestinal development and physiology. However, to-date, the majority of studies characterizing the gut microbiome has relied on stool samples, thereby limiting insights into the regionality of the gut and how its microbiota differs along its length. As a result, this project seeks to profile the adjacent microbiota of various regions along the intestinal tract from pediatric intestinal tissue and their associated mucosal washes, enabling insights into tissue-specific microbiomes. Due to the expected low microbial biomass of these samples, donor stool (when available) will also be metagenomically profiled as positive controls, which will enable us to benchmark our low-biomass processing methods with existing protocols. By sampling pediatric patients of diverse ages and health statuses, this metagenomic data will also be valuable for understanding the gut microbiome of the developing human gut across time and space. ","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-03-24T10:00:07+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008082","title":"Whole-genome sequencing study of uveal melanoma","description":"Uveal melanoma is the most common primary intraocular cancer, characterized by metastasis-related mortality. Here, we explored whole-genome sequences from 40 primary uveal melanomas to illustrate the landscape of genomic mutations and investigate their association with prognosis.","abstract":"Uveal melanoma is the most common primary intraocular cancer, characterized by metastasis-related mortality. Here, we explored whole-genome sequences from 40 primary uveal melanomas to illustrate the landscape of genomic mutations and investigate their association with prognosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008083","title":"Brain_Disease_Wellcome_Leap_Delta_Tissue_ATAC","description":"Single cell and spatial multi-omic atlas of glioblastoma","abstract":"Cancer cells display heterogeneous and dynamic states in glioblastoma, but how these malignant states arise and whether they follow a tractable cellular trajectory across tumours is poorly understood. Here, we generate a deep single cell and spatial multi-region atlas of 12 isocitrate dehydrogenase wild-type (IDH-wt) primary glioblastomas that integrates transcriptomic, epigenomic and genomic analysis to comprehensively characterise their tumour heterogeneity. The datasets in this study include sequencing data from single nuclei joint transcriptome- and chromatin accessibility-sequencing (“multiome” snRNA+ATAC-seq, 10x Genomics).","study_type":"Gene Regulation Study","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-03-24T16:51:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008084","title":"Intratumoral Ploidy Dynamics in HCC","description":"Hepatocellular carcinoma (HCC) ranks as the fourth leading cause of cancer-related deaths. Effective therapies are limited, highlighting the critical need for stratification biomarkers to improve prognosis and predict treatment response. Polyploidization or hyperploidization, an early event observed in many solid cancers, may offer such potential. Here, we developed a new high throughput in situ quantitative approach to assess HCC ploidy profiles. This novel method highlights the presence of both Diploid (DP-) and Hyperploid (HP-) HCCs. RNA-seq profiling classified hyperploid HCCs as belonging to the proliferation subclass, predicting unfavourable clinical outcomes, and revealing a gene expression signature indicative of stemness. Spatially reconstructing nuclear ploidy also revealed DP/HP-HCCs with hyperploid nuclei forming discrete clusters within a predominantly diploid background. Remarkably, these emerging hyperploid foci shared a portion of their transcriptomic programme with fully developed hyperploid HCCs and displayed a signature of genomic instability, including upregulation of multiple DNA repair pathways in response to replication-associated DNA damage. Importantly, spatial transcriptomics of DP/HP HCC demonstrated that hyperploid tumor hepatocytes arise through whole-genome doubling of diploid tumor hepatocytes. Collectively, our findings underscore the prognostic value of nuclear ploidy profiling in HCC and suggest that hyperploid HCCs evolve clonally from intratumor hyperploid foci during tumor progression.","abstract":"Hepatocellular carcinoma (HCC) ranks as the fourth leading cause of cancer-related deaths. Effective therapies are limited, highlighting the critical need for stratification biomarkers to improve prognosis and predict treatment response. Polyploidization or hyperploidization, an early event observed in many solid cancers, may offer such potential. Here, we developed a new high throughput in situ quantitative approach to assess HCC ploidy profiles. This novel method highlights the presence of both Diploid (DP-) and Hyperploid (HP-) HCCs. RNA-seq profiling classified hyperploid HCCs as belonging to the proliferation subclass, predicting unfavourable clinical outcomes, and revealing a gene expression signature indicative of stemness. Spatially reconstructing nuclear ploidy also revealed DP/HP-HCCs with hyperploid nuclei forming discrete clusters within a predominantly diploid background. Remarkably, these emerging hyperploid foci shared a portion of their transcriptomic programme with fully developed hyperploid HCCs and displayed a signature of genomic instability, including upregulation of multiple DNA repair pathways in response to replication-associated DNA damage. Importantly, spatial transcriptomics of DP/HP HCC demonstrated that hyperploid tumor hepatocytes arise through whole-genome doubling of diploid tumor hepatocytes. Collectively, our findings underscore the prognostic value of nuclear ploidy profiling in HCC and suggest that hyperploid HCCs evolve clonally from intratumor hyperploid foci during tumor progression.","study_type":"Other","pubmed_ids":[41297676],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008085","title":"Optical genome mapping enables accurate testing of large repeat expansions","description":"Optical genome mapping was performed for 85 samples with large repeat expansions in RFC1, DMPK, or CNBP. Subsequently we determined exact repeat sizes and repeat stability.","abstract":"Short tandem repeats (STRs) are common variations in human genomes that frequently expand or contract, causing genetic disorders, mainly when expanded. Traditional diagnostic methods for identifying these expansions, such as repeat-primed PCR and Southern blotting, are often labor-intensive, locus-specific, and are unable to precisely determine long repeat expansions. Sequencing-based methods, though capable of genome-wide detection, are limited by inaccuracy (short-read technologies) and high associated costs (long-read technologies). This study evaluated optical genome mapping (OGM) as an efficient, accurate approach for measuring STR lengths and assessing somatic stability in 85 samples with known pathogenic repeat expansions in DMPK, CNBP, and RFC1, causing myotonic dystrophy types 1 and 2 and cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), respectively. Three workflows—manual de novo assembly, local guided assembly (local-GA), and a molecule distance script—were applied, of which the latter two were developed as part of this study to assess the repeat sizes and somatic repeat stability. OGM successfully identified 84/85 (98.8%) of the pathogenic expansions, distinguishing between wild-type and expanded alleles or between two expanded alleles in recessive cases, with greater accuracy than standard of care (SOC) for long repeats and no apparent upper size limit. Notably, OGM detected somatic instability in a subset of DMPK, CNBP, and RFC1 samples. These findings suggest OGM could advance diagnostic accuracy for large repeat expansions, providing a more comprehensive genome-wide assay for repeat expansion disorders by measuring exact repeat lengths and somatic instability across multiple loci simultaneously.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008086","title":"Genetic Landscape of Hepatocellular Adenoma","description":"Hepatocellular adenoma (HCA) is a rare liver tumor with variable risk of complications and malignant transformation. We performed a comprehensive genetic analysis in a large patient cohort, combining germline and somatic data. Common and rare inherited variants were associated with specific clinical features, while somatic mutations contributed to the molecular classification of tumor subtypes. Integration of both germline and somatic profiles revealed distinct patterns linked to multifocality, histology, and subtype distribution. These results refine the genetic architecture of HCA and support a classification framework based on combined molecular features to improve diagnosis and risk stratification.","abstract":"Hepatocellular adenoma (HCA) is a rare liver tumor with variable risk of complications and malignant transformation. We performed a comprehensive genetic analysis in a large patient cohort, combining germline and somatic data. Common and rare inherited variants were associated with specific clinical features, while somatic mutations contributed to the molecular classification of tumor subtypes. Integration of both germline and somatic profiles revealed distinct patterns linked to multifocality, histology, and subtype distribution. These results refine the genetic architecture of HCA and support a classification framework based on combined molecular features to improve diagnosis and risk stratification.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008087","title":"Single_cell_RNA_seq_using_Pip_seq__Particle_templated_instant_partition_sequencing__from_peripheral_blood_mononuclear_cells_in_a_South_Asian_cohort","description":"Single cell RNA-seq was generated from peripheral blood mononuclear cells (PBMC) using the Fluent Bioscience PiP-seq technology. PBMC were obtained from donors as part of the Genes and Health consortium. These are individuals of Pakistani and Bangladeshi heritage collected from London and Bradford in the United Kingdom. The dataset consists of approximately 100 donors at a depth of &gt;10,000 cells per donor. Sequencing was performed on the Illumina Novaseq platform to an average depth of 35,000 reads per cell. Donors were pooled and deconvoluted into individual datasets using cohort genotypes with CellSNP and Vireo software. \n\nThis data is held in the EGA under managed access in concordance with terms set out by the Genes and Health consortium.","abstract":"Single cell RNA-seq was generated from peripheral blood mononuclear cells (PBMC) using the Fluent Bioscience PiP-seq technology. PBMC were obtained from donors as part of the Genes and Health consortium. These are individuals of Pakistani and Bangladeshi heritage collected from London and Bradford in the United Kingdom. The dataset consists of approximately 100 donors at a depth of &gt;10,000 cells per donor. Sequencing was performed on the Illumina Novaseq platform to an average depth of 35,000 reads per cell. Donors were pooled and deconvoluted into individual datasets using cohort genotypes with CellSNP and Vireo software. \n\nThis data is held in the EGA under managed access in concordance with terms set out by the Genes and Health consortium.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008088","title":"Stratton__WGS___CRC","description":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. ","abstract":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. ","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008089","title":"LCM_WES_wilson_NovaSeqX","description":"Whole exome sequencing of laser capture microdissected hepatocytes from donors with Wilson disease.","abstract":"Investigating the driver landscape across chronic liver disease, comparing histological correlate to clonal architecture.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008090","title":"PacBio_NanoSeq_Development","description":"R&amp;D project testing the compatibility of NanoSeq library preparation processes with PacBio sequencing.","abstract":"This study will use Targeted NanoSeq of ccRCC tumours to characterise their deep subclonal landscape and patterns of selection.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008091","title":"Hca_Gut_Teichmann_Mm_Spatial_Managed_Access","description":"This study aims to profile gut tissue of infants, primarily those born preterm (defined as babies born alive before 37 weeks of pregnancy are completed). To that end, we will generate spatial transcriptomic data of leftover intestinal tissue collected during resection surgeries, which will enable a better understanding of early life gut development. \n","abstract":"The gastrointestinal (GI) tract performs diverse roles related to digestion, barrier function, immune regulation, and the absorption of nutrients. As a result, understanding its development and maturation is important for ensuring proper health and growth throughout the lifespan. While we have previously generated data characterizing fetal, pediatric, and adult intestinal development, we aim to further expand this dataset with samples from preterm and neonatal gut. This data will be critical in evaluating the possibility of multiple developmental conditions in preterm infants, including necrotizing enterocolitis. \n","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008092","title":"Whole exome and RNA sequencing of organoid samples derived from TRACERx patients","description":"Immune checkpoint blockade in non-small cell lung cancer (NSCLC) rarely leads to complete tumour remission, suggesting that tumours harbour subpopulations of cancer cells that can escape immune predation. However, while tumours consist of multiple genetically distinct clones, the extent to which separate tumour subclones differ intrinsically in their functional capacity for immune evasion remains largely unexplored. This has been challenging to address due to an inability to isolate and propagate individual tumour subclones from human cancers. Here, we leverage the multi-region TRACERx lung cancer evolution study to generate a patient-derived platform that allows the functional analysis of immune escape at single clone resolution. We generated libraries of &gt;20 separate NSCLC organoid lines per patient by isolating individual (clonal) organoids established from multiple spatially separated tumour regions. Each organoid subline was co-cultured with autologous tumour infiltrating lymphocytes (TIL) to evaluate their capacity to elicit a T cell response. Organoid lines derived from separate tumour regions, or from single clones within individual regions, differ vastly in their capacity to elicit a T cell response, showing the coexistence of intrinsically immune evading (‘hot’) and non-evading (‘cold’) clones in the same primary tumour. Organoid lines escaping T cell recognition represent genetically and transcriptionally unique subclones with a distinct evolutionary history, showing that evolutionary sculpting of subclonal diversity can have functional consequences for anti-tumour immunity. Notably, the identification of immune-evasive subclones would not have been possible using computational approaches alone, highlighting the unique value of functional co-culture platforms. This patient-derived functional co-culture platform reveals that tumour evolution can give rise to distinct cancer clones with intrinsic differences in immune evasion capacity and provides an approach to prospectively identify, isolate and characterise immune evading subclones from patients with cancer.","abstract":"Immune checkpoint blockade in non-small cell lung cancer (NSCLC) rarely leads to complete tumour remission, suggesting that tumours harbour subpopulations of cancer cells that can escape immune predation. However, while tumours consist of multiple genetically distinct clones, the extent to which separate tumour subclones differ intrinsically in their functional capacity for immune evasion remains largely unexplored. This has been challenging to address due to an inability to isolate and propagate individual tumour subclones from human cancers. Here, we leverage the multi-region TRACERx lung cancer evolution study to generate a patient-derived platform that allows the functional analysis of immune escape at single clone resolution. We generated libraries of &gt;20 separate NSCLC organoid lines per patient by isolating individual (clonal) organoids established from multiple spatially separated tumour regions. Each organoid subline was co-cultured with autologous tumour infiltrating lymphocytes (TIL) to evaluate their capacity to elicit a T cell response. Organoid lines derived from separate tumour regions, or from single clones within individual regions, differ vastly in their capacity to elicit a T cell response, showing the coexistence of intrinsically immune evading (‘hot’) and non-evading (‘cold’) clones in the same primary tumour. Organoid lines escaping T cell recognition represent genetically and transcriptionally unique subclones with a distinct evolutionary history, showing that evolutionary sculpting of subclonal diversity can have functional consequences for anti-tumour immunity. Notably, the identification of immune-evasive subclones would not have been possible using computational approaches alone, highlighting the unique value of functional co-culture platforms. This patient-derived functional co-culture platform reveals that tumour evolution can give rise to distinct cancer clones with intrinsic differences in immune evasion capacity and provides an approach to prospectively identify, isolate and characterise immune evading subclones from patients with cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-04-08T11:39:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008093","title":"WGS chromosomal integrity check of engineered CRISRPi/a-NGN2 hiPSC clones","description":"low coverage WGS of knock-in hiPSC lines to confirm chromosomal integrity. Inducible NGN2 from the AAVS1 safe-harbour (via TALENs). CRISPRi/a expression cassettes inserted to the CLYBL safe-harbour using TALENs.","abstract":"genetic modification design;genotype design","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008094","title":"Phenotypic CRISPRi screens to infer cell fitness effects, ROS accumulation and cell cycle progression of perturbing schizophrenia risk genes","description":"Human iPSCs were transduced with the pool of gRNAs (n = 275) targeting 65 schizophrenia risk genes at a low MOI (0.2). After selection with puromycin, cells were either maintained as hiPSCs, or differentiated to neural progenitors or induced neurons. Seven days post differentiation induction, cells were harvested and gRNA distributions compared via Amplicon-seq. As additional negative controls, gRNA Amplicon-seq libraries were prepared from the plasmid DNA and from cell lines which lack the expression of a Cas effector protein (HEK293T, NIH-3T3).   sorted/unsorted populations of indicated cells after incorporation with EdU and following CRISPRi of 65 schizophrenia risk genes. Aim is to assess if specific CRISPRi perturbations impact cell cycle and proliferation in the indicated hiPSC-derived neuronal cell types.For the phenotypic EdU-incorporation screen, hiPSCs, NPCs and induced neurons with transduced with the pool of gRNAs were gated for cells in G1-, S-, or G2-phase and sorted &gt;1,000-fold representation. Cells were washed with PBS and pellets snap frozen in liquid nitrogen for subsequent genomic DNA extraction and Amplicon-seq library preparation of gRNAs.   hiPSCs were labelled for lipophilic and hydrophilic compartments of ROS accumulation in hiPSC-derived NPCs and neurons following the repression of 65 schizophrenia-associated genes.    Cells were harvested and FAC-sorted, while binning them based on their ROS accumulation into fluorescently low (0 – 30 % of distribution), medium (35 – 70 %) and high (75 – 100 %) groups. Cells were sorted above a representation of 1,000x, washed with PBS and cell pellets snap frozen in liquid nitrogen for subsequent genomic DNA extraction and Amplicon-seq library preparation of gRNAs.","abstract":"genetic modification design;development or differentiation design;compound treatment design","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008095","title":"DERMATLAS_BCC_RNA","description":"This experiment uses single-cell and spatial transcriptomics to map the molecular landscape of 70+ skin cancers, aiding diagnosis, treatment, and understanding of disease progression.","abstract":"Aim to understand the genetics and genomics of over 70 different skin cancers to improve clinical practice, patient management and targeted therapies. This project wil generate single cell and spatial transcriptomic data to map the molecular landscape of these skin tumours to improve our understanding of disease. This dataset will also provide a foundational resource to understand the finer differences between tumour types and also in non-metastatic vs metastatic disease.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008096","title":"Moonshot CRC samples with RRBS and WGBS","description":"Aberrant methylation is a hallmark of cancer, but bulk tumor data is confounded by admixed normal cells and copy number changes. Here, we introduce Copy number-Aware Methylation Deconvolution Analysis of Cancers (CAMDAC; https://github.com/VanLoo-lab/CAMDAC), which outputs tumor purity, allele-specific copy number, and deconvolved methylation rates. We apply CAMDAC to 122 multi-region samples from 38 TRACERx non-small cell lung cancers profiled by reduced representation bisulfite sequencing (RRBS), and 6 samples from Moonshot colorectal cancers with both RRBS and whole genome bisulfite sequencing. CAMDAC copy number profiles parallel those derived from genome sequencing and highlight widespread chromosomal instability. Deconvolved polymorphism-independent methylation rates enable unbiased tumor-normal and tumor-tumor differential methylation calling. Read phasing validates CAMDAC methylation rates and directly links genotype and epitype. We show increased epigenetic instability in adenocarcinoma vs. squamous cell carcinoma, frequent hypermethylation at sites carrying somatic mutations, and parallel copy number losses and methylation changes at imprinted loci. Unlike bulk methylomes, CAMDAC profiles recapitulate tumor phylogenies and evidence distinct patterns of epigenetic heterogeneity in lung cancer. ","abstract":"Aberrant methylation is a hallmark of cancer, but bulk tumor data is confounded by admixed normal cells and copy number changes. Here, we introduce Copy number-Aware Methylation Deconvolution Analysis of Cancers (CAMDAC; https://github.com/VanLoo-lab/CAMDAC), which outputs tumor purity, allele-specific copy number, and deconvolved methylation rates. We apply CAMDAC to 122 multi-region samples from 38 TRACERx non-small cell lung cancers profiled by reduced representation bisulfite sequencing (RRBS), and 6 samples from Moonshot colorectal cancers with both RRBS and whole genome bisulfite sequencing. CAMDAC copy number profiles parallel those derived from genome sequencing and highlight widespread chromosomal instability. Deconvolved polymorphism-independent methylation rates enable unbiased tumor-normal and tumor-tumor differential methylation calling. Read phasing validates CAMDAC methylation rates and directly links genotype and epitype. We show increased epigenetic instability in adenocarcinoma vs. squamous cell carcinoma, frequent hypermethylation at sites carrying somatic mutations, and parallel copy number losses and methylation changes at imprinted loci. Unlike bulk methylomes, CAMDAC profiles recapitulate tumor phylogenies and evidence distinct patterns of epigenetic heterogeneity in lung cancer. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008097","title":"Combined MEK and PARP inhibition enhances radiation response in rectal cancer","description":"Rectal cancer is most frequently diagnosed at a locally advanced stage and treated by neoadjuvant chemoradiation. Current efforts to improve treatment outcome are focused on intensifying neoadjuvant chemotherapy, which is however associated with higher levels of toxicity. To discover alternative strategies, we established patient-derived rectal cancer organoids (PDOs) that reflect clinical radiosensitivity and used these organoids to screen 1596 drug-radiation combinations. We found that inhibitors of RAS-MAPK signaling, especially MEK inhibitors, strongly enhance radiation response. Mechanistically, MEK inhibitors suppressed radiation-induced activation of RAS-MAPK signaling, and selectively downregulated RAD51, a key component of the homologous recombination DNA repair pathway. Through testing drug-drug-radiation combinations in organoids and cell lines, we identified that a combined PARP and MEK inhibition can further enhance radiosensitivity of colorectal cancers, which was confirmed in mouse xenograft models. Our data support clinical testing of MEK and PARP combination therapy with radiation in locally advanced rectal cancers as an alternative to chemoradiation","abstract":"Rectal cancer is most frequently diagnosed at a locally advanced stage and treated by neoadjuvant chemoradiation. Current efforts to improve treatment outcome are focused on intensifying neoadjuvant chemotherapy, which is however associated with higher levels of toxicity. To discover alternative strategies, we established patient-derived rectal cancer organoids (PDOs) that reflect clinical radiosensitivity and used these organoids to screen 1596 drug-radiation combinations. We found that inhibitors of RAS-MAPK signaling, especially MEK inhibitors, strongly enhance radiation response. Mechanistically, MEK inhibitors suppressed radiation-induced activation of RAS-MAPK signaling, and selectively downregulated RAD51, a key component of the homologous recombination DNA repair pathway. Through testing drug-drug-radiation combinations in organoids and cell lines, we identified that a combined PARP and MEK inhibition can further enhance radiosensitivity of colorectal cancers, which was confirmed in mouse xenograft models. Our data support clinical testing of MEK and PARP combination therapy with radiation in locally advanced rectal cancers as an alternative to chemoradiation","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008098","title":"Sequencing_Red_Cell_Micronuclei_WGS","description":"This project aims to characterise through genomic sequencing a type of micronucleus (MN) within red blood cells called Howell Jolly (HJ) bodies. These nuclear remnants are thought to be a result of chromosomal instability and by understanding their genetic composition we hope to delineate the aetiology of their formation. ","abstract":"Aim: To isolate MN-containing red cells and determine the origin and DNA composition of these structures using single cell sequencing. \nMethods: A variety of splenectomised patients will be recruited for sample donation. Heparinised human whole blood will be fixed in methanol. The MN-containing mature red cells (isolated on the basis of CD71-negativity and and PI-positivity) will be individually sorted into a 384 well plate and prepared for genomic sequencing. A portion of MN-containing red cells will also be sequenced in bulk. \nAnticipated results: We expect that the types of genomic DNA fragments elucidated from this sequencing will provide insights into regions of chromosomal fragility. Different patterns of DNA damage may also be seen depending on the clinical background of the donor. ","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008099","title":"ChIPseq data (H3K27me3, H3K4me1, H3K4me3, H3K9me3) for 3 patient derived cell lines","description":"TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC).","abstract":"TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008100","title":"Targeted scifi-RNA-seq of 65 schizophrenia-implicated genes in NPCs and neurons (TAP-seq)","description":"Targeted single-cell sequencing (TAP-seq; Schraivogel et al. 2020) of 65 schizophrenia risk genes with CRISPRi perturbations in hiPSC-derived NPCs and neurons.","abstract":"genetic modification design","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008101","title":"Chromatin accessibility profiling of hiPSC-derived NPCs and induced neurons following CRISPRa of TCF4 and ZEB1","description":"hiPSCs (n=3) were transduced with two gRNAs targeting the TSS of TCF4, ZEB1 or with non-targeting control gRNAs. After puromycin selection, cells were differentiated to NPCs or induced neurons. 50-100K cells were collected at day 7 after initiating differentiation and bulk ATAC-seq libraries were prepared using in-house produced Tn5.","abstract":"development or differentiation design;genotype design;genetic modification design","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008102","title":"Gene expression profiling of hiPSCs and derived NPCs following CRISPRi of EHMT2 (or NT-ctrl)","description":"hiPSCs were transduced with non-targeting control gRNA-lentiviruses (NT-ctrl) or with gRNA-lentiviruses targeting the TSS of EHMT2. After puromycin selection, cells were either maintained as hiPSCs or differentiated to NPCs via dual SMADi.  At day 7 of differentiation, cells were harvested, total RNA extracted and mRNA-sequencing libraries prepared.","abstract":"genetic modification design;development or differentiation design","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008103","title":"Assessing the suitability of formalin-fixed paraffin-embedded (FFPE) tissue for genome-wide association studies (GWAS)","description":"This study evaluates the feasibility of conducting genome-wide association studies (GWAS) using DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue. Genotyping results from paired FFPE and blood samples were compared using both microarray technology and low-coverage whole-genome sequencing (lcWGS). The analysis demonstrated high concordance between FFPE- and blood-derived genotypes. Although both platforms performed well, microarrays achieved significantly higher recall and precision and currently offer greater cost-effectiveness and computational efficiency. These findings support the suitability of FFPE-derived DNA for GWAS, with microarrays representing the preferred approach at present. However, the broader variant detection enabled by lcWGS may represent an additional advantage to be explored in future studies, particularly in diverse populations.","abstract":"This study evaluates the feasibility of conducting genome-wide association studies (GWAS) using DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue. Genotyping results from paired FFPE and blood samples were compared using both microarray technology and low-coverage whole-genome sequencing (lcWGS). The analysis demonstrated high concordance between FFPE- and blood-derived genotypes. Although both platforms performed well, microarrays achieved significantly higher recall and precision and currently offer greater cost-effectiveness and computational efficiency. These findings support the suitability of FFPE-derived DNA for GWAS, with microarrays representing the preferred approach at present. However, the broader variant detection enabled by lcWGS may represent an additional advantage to be explored in future studies, particularly in diverse populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-04-14T16:09:21+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008104","title":"Somatic mutations in ALS genes in the motor cortex of sporadic ALS patients","description":"Several lines of evidence suggest that amyotrophic lateral sclerosis (ALS) pathology starts focally and spreads within the central nervous system (CNS). We leveraged DNA and RNA sequencing data from ALS autopsy tissue to explore the presence of somatic mosaic variants in sporadic ALS (sALS) cases. Deep targeted sequencing of known ALS disease genes from motor cortex tissue revealed enrichment of somatic variants in sALS compared to familial ALS (fALS) with a monogenic cause and an increased pathogenicity of mosaic mutations in known ALS mutational hot spots. Experimental validation of the\nvariants identified that the somatic FUS variant p.E516X leads to nucleo-cytoplasmic mislocalization and aggregation. Additionally, somatic variant calling from single-cell RNA-sequencing data of sALS tissue showed an accumulation of somatic variants in excitatory neurons. Collectively, using a multi-modal approach, our findings suggest that somatic mutations within the motor cortex, especially in excitatory neurons, may contribute to the development of sALS.","abstract":"Several lines of evidence suggest that amyotrophic lateral sclerosis (ALS) pathology starts focally and spreads within the central nervous system (CNS). We leveraged DNA and RNA sequencing data from ALS autopsy tissue to explore the presence of somatic mosaic variants in sporadic ALS (sALS) cases. Deep targeted sequencing of known ALS disease genes from motor cortex tissue revealed enrichment of somatic variants in sALS compared to familial ALS (fALS) with a monogenic cause and an increased pathogenicity of mosaic mutations in known ALS mutational hot spots. Experimental validation of the\nvariants identified that the somatic FUS variant p.E516X leads to nucleo-cytoplasmic mislocalization and aggregation. Additionally, somatic variant calling from single-cell RNA-sequencing data of sALS tissue showed an accumulation of somatic variants in excitatory neurons. Collectively, using a multi-modal approach, our findings suggest that somatic mutations within the motor cortex, especially in excitatory neurons, may contribute to the development of sALS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008105","title":"Sequencing_tonsil_epithelium_Dupseq","description":"Tonsils can undergo long term chronic inflammation.  We wish to investigate if/how this impacts the epithelia landscape.  Tonsils from patients undergoing tonsillectomy will be collected and the epithelia removed.  The epithelia will be dissected into 2mm2 grids and Dupseq performed to understand burden and signatures.","abstract":"Tonsils can undergo long term chronic inflammation.  We wish to investigate if/how this impacts the epithelia landscape.  Tonsils from patients undergoing tonsillectomy will be collected and the epithelia removed.  The epithelia will be dissected into 2mm2 grids and Dupseq performed to understand burden and signatures.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008106","title":"Spatial and multi-omic profiling reveals genes and pathways associated with cytotoxic lymphocyte infiltration in malignant rhabdoid tumor","description":"Malignant rhabdoid tumors (MRTs) are aggressive pediatric cancers with poor outcomes. MRTs exhibit low tumor mutational burden, yet recent studies reported immune cell infiltration. Here, we used spatial transcriptomics and multi-omics to explore molecular and cellular features associated with immune cell infiltration in MRT. We identified a diverse set of tumor antigens (TAs) expressed by MRT cells and showed that genes associated with the IRF1 signaling pathway and antigen processing/presentation are significantly correlated with cytotoxic lymphocyte infiltration. A subset of MRTs with high CD8+ T cell infiltration also exhibited increased expression of a skeletal muscle developmental program. Additionally, we found that the M1/M2 macrophage ratio strongly correlated with cytotoxic lymphocyte infiltration and identified genes and regulatory networks that potentially play roles in M2-like tumor-associated macrophages. ","abstract":"Malignant rhabdoid tumors (MRTs) are aggressive pediatric cancers with poor outcomes. MRTs exhibit low tumor mutational burden, yet recent studies reported immune cell infiltration. Here, we used spatial transcriptomics and multi-omics to explore molecular and cellular features associated with immune cell infiltration in MRT. We identified a diverse set of tumor antigens (TAs) expressed by MRT cells and showed that genes associated with the IRF1 signaling pathway and antigen processing/presentation are significantly correlated with cytotoxic lymphocyte infiltration. A subset of MRTs with high CD8+ T cell infiltration also exhibited increased expression of a skeletal muscle developmental program. Additionally, we found that the M1/M2 macrophage ratio strongly correlated with cytotoxic lymphocyte infiltration and identified genes and regulatory networks that potentially play roles in M2-like tumor-associated macrophages. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008107","title":"This study generated Oxford Nanopore long read sequencing data of cancer cell line mixtures for validating long-read variant calls in cancer genomics","description":"Long-read sequencing (LRS) improves genome alignment and facilitates resolving variants in complex genomic regions, making it a promising approach for cancer variant detection and biomarker discovery. Here, we evaluate the performance of LRS to detect somatic variants across different tumour purities and sequencing depths by comparing to somatic variants from short-read sequencing. We generated experimental mixtures of cancer cell lines and matched normal cell lines to simulate 10 tumour purities (ranging from 0 to 100% tumour content). This resulted in 22 samples which were sequenced using whole genome LRS to a targeted depth of 60x and somatic variants were identified. We downsampled sequencing data to explore the optimal read depth for somatic variant detection. Our results show that long-read variant calling tools achieve recall rates comparable to short-read gold standards. While a tumour sequencing depth of 30x to 60× is generally sufficient for detecting common variants, particularly structural variants (SVs), sequencing the matched normal sample at adequate depth is crucial for accuracy. Notably, we found variants unique to LRS that may represent real and previously undetected events. This study highlights key factors for optimising cancer genome sequencing with LRS and provides a comprehensive dataset of cell line mixtures for future research and tool development.","abstract":"Long-read sequencing (LRS) improves genome alignment and facilitates resolving variants in complex genomic regions, making it a promising approach for cancer variant detection and biomarker discovery. Here, we evaluate the performance of LRS to detect somatic variants across different tumour purities and sequencing depths by comparing to somatic variants from short-read sequencing. We generated experimental mixtures of cancer cell lines and matched normal cell lines to simulate 10 tumour purities (ranging from 0 to 100% tumour content). This resulted in 22 samples which were sequenced using whole genome LRS to a targeted depth of 60x and somatic variants were identified. We downsampled sequencing data to explore the optimal read depth for somatic variant detection. Our results show that long-read variant calling tools achieve recall rates comparable to short-read gold standards. While a tumour sequencing depth of 30x to 60× is generally sufficient for detecting common variants, particularly structural variants (SVs), sequencing the matched normal sample at adequate depth is crucial for accuracy. Notably, we found variants unique to LRS that may represent real and previously undetected events. This study highlights key factors for optimising cancer genome sequencing with LRS and provides a comprehensive dataset of cell line mixtures for future research and tool development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-04-17T08:05:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008108","title":"A cycling, progenitor-like cell population at the root of atypical teratoid rhabdoid tumor subtype differentiation trajectories.","description":"Background: Atypical teratoid rhabdoid tumors (ATRTs), characterized by the loss of SMARCB1, are among the most lethal pediatric central nervous system (CNS) tumors. Three molecular subtypes have been identified, each defined by distinct molecular and clinical features. No subtype-specific treatments are available, highlighting the necessity to better understand inter- and intra-subtype heterogeneity.\n\nMethods: We generated a single-nucleus transcriptome atlas of ATRTs, validated by single-cell ATAC-seq and spatial transcriptomics, to study subtype-specific differentiation trajectories.\n\nResults: We identified brain progenitor-like expression profiles within unique subtype-specific differentiation lineages. A shared cycling, progenitor-like cell population, interspersed throughout tumors, was observed across all ATRT samples. Moreover, we demonstrate that subtype-specific differentiation trajectories can be induced pharmacologically in ATRT tumoroids directing tumor cells towards a non-proliferative, mature phenotype.\n\nConclusions: Our study reveals that ATRT subtypes exhibit signaling trajectories mirroring normal fetal brain development, enabling the development of maturation therapies tailored towards ATRTs.\n","abstract":"Background: Atypical teratoid rhabdoid tumors (ATRTs), characterized by the loss of SMARCB1, are among the most lethal pediatric central nervous system (CNS) tumors. Three molecular subtypes have been identified, each defined by distinct molecular and clinical features. No subtype-specific treatments are available, highlighting the necessity to better understand inter- and intra-subtype heterogeneity.\n\nMethods: We generated a single-nucleus transcriptome atlas of ATRTs, validated by single-cell ATAC-seq and spatial transcriptomics, to study subtype-specific differentiation trajectories.\n\nResults: We identified brain progenitor-like expression profiles within unique subtype-specific differentiation lineages. A shared cycling, progenitor-like cell population, interspersed throughout tumors, was observed across all ATRT samples. Moreover, we demonstrate that subtype-specific differentiation trajectories can be induced pharmacologically in ATRT tumoroids directing tumor cells towards a non-proliferative, mature phenotype.\n\nConclusions: Our study reveals that ATRT subtypes exhibit signaling trajectories mirroring normal fetal brain development, enabling the development of maturation therapies tailored towards ATRTs.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-04-17T09:16:59+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008109","title":"Individual genotyping data for 1,637 patients in treatment for AUD and 795 controls","description":"Two case samples are included in this study.The first one corresponds to 933 participants who met the diagnostic criteria for AUD according to the DSM-5 that were recruited among treatment-seeking subjects at six different Hospitals from the Addictive Disorders Network (Red de Trastornos Adictivos, RTA). The second one is constituted by 704 alcohol abuse/dependence cases, according to DSM-IV criteria, from Galicia, North West Spain. Subjects were mainly patients attending Addictive Disorders Assistance Units from the main healthcare areas of Galicia. and blood banks. \n\nControl data corresponds to 795 Galician, mainly from blood donors at the Galician Transfusion Center of Santiago de Compostela. \n\nThe RTA samples were genotyped with the Axiom Spain Biobank Array (ThermoFisher Scientific), which contains ~750,000 SNPs across the genome. The Galician samples were genotyped with the Infinium PsychArray BeadChip (Illumina), comprising ~550,000 SNPs. ","abstract":"Two case samples are included in this study.The first one corresponds to 933 participants who met the diagnostic criteria for AUD according to the DSM-5 that were recruited among treatment-seeking subjects at six different Hospitals from the Addictive Disorders Network (Red de Trastornos Adictivos, RTA). The second one is constituted by 704 alcohol abuse/dependence cases, according to DSM-IV criteria, from Galicia, North West Spain. Subjects were mainly patients attending Addictive Disorders Assistance Units from the main healthcare areas of Galicia. and blood banks. \n\nControl data corresponds to 795 Galician, mainly from blood donors at the Galician Transfusion Center of Santiago de Compostela. \n\nThe RTA samples were genotyped with the Axiom Spain Biobank Array (ThermoFisher Scientific), which contains ~750,000 SNPs across the genome. The Galician samples were genotyped with the Infinium PsychArray BeadChip (Illumina), comprising ~550,000 SNPs. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008110","title":"Multiome sequencing of primary colon tissue and derived organoids","description":"Multiome (ATAC + RNA) sequencing of primary colon tissue and organoids derived from the same donors.","abstract":"Multiome (ATAC + RNA) sequencing of primary colon tissue and organoids derived from the same donors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-04-25T11:55:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008111","title":"Validation of cfDNA fragmentome analyses for early detection of liver cancer","description":null,"abstract":"Hepatocellular carcinoma (HCC) is the third leading cause of cancer death globally and its prevalence is increasing in North America and Europe due to metabolic and emerging risk factors.  Here, we show that the DELFI (DNA evaluation of fragments for early interception) approach using cell-free DNA (cfDNA) fragmentation profiles and machine learning can detect HCC across diverse populations and can be enhanced by incorporating patient clinical risk and protein concentrations from the same blood sample.  Using a locked DELFI model trained on plasma samples from 208 high-risk patients with or without HCC we analyzed 375 individuals in two distinct cohorts, including 244 participants with HCC and 132 without cancer, and found that DELFI detected HCC across all stages, diverse etiologies and outperformed the commonly used alpha-fetoprotein (AFP) marker. A combined approach using DELFI, AFP, and clinical risk achieved a high sensitivity in early and late-stage cancers in both cohorts, and was more sensitive than reported AFP and ultrasound performance for early-stage disease.  Characteristics of the cfDNA fragmentome, including genome-wide chromatin and mutational profiles, were altered in patients with HCC, including those with metabolic risk factors and aflatoxin exposure. This study validates the genome-wide fragmentome approach for non-invasive detection of HCC and provides insights into the origins of altered cfDNA and circulating proteins for populations at risk.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-04-26T03:03:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008112","title":"Cancer of Low survival and UnMet Need – Pathologist Initiated","description":"Despite significant advances in diagnostic cancer histopathology, a subset of tumors remain unable to be classified using WHO criteria. The resulting diagnostic uncertainty can result in inappropriate clinical management and negative patient outcomes. We investigated whether combining histopathology with whole genome and transcriptome sequencing (WGTS) could improve the classification of tumors that posed diagnostic dilemmas despite extensive histopathology and standard molecular work-up at a quaternary oncology center. We successfully sequenced 45 tumors from an initial set of 54 unclassified tumors (83% success rate). A confident diagnosis was made for 38/45 tumors (84%). Additionally, potential treatment targets were identified in 21/45 tumors (47%). Theoretical comparison with alternative assays demonstrated that WGTS was uniquely capable of detecting critical diagnostic findings in 15/38 tumors (39%). This work supports augmenting histopathology and standard molecular pathology with WGTS in the classification of difficult-to-diagnose tumors.","abstract":"Despite significant advances in diagnostic cancer histopathology, a subset of tumors remain unable to be classified using WHO criteria. The resulting diagnostic uncertainty can result in inappropriate clinical management and negative patient outcomes. We investigated whether combining histopathology with whole genome and transcriptome sequencing (WGTS) could improve the classification of tumors that posed diagnostic dilemmas despite extensive histopathology and standard molecular work-up at a quaternary oncology center. We successfully sequenced 45 tumors from an initial set of 54 unclassified tumors (83% success rate). A confident diagnosis was made for 38/45 tumors (84%). Additionally, potential treatment targets were identified in 21/45 tumors (47%). Theoretical comparison with alternative assays demonstrated that WGTS was uniquely capable of detecting critical diagnostic findings in 15/38 tumors (39%). This work supports augmenting histopathology and standard molecular pathology with WGTS in the classification of difficult-to-diagnose tumors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-04-28T05:30:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008113","title":"Hepatoblastoma_Cambridge_Behjati_WellcomeCore_EMseq","description":"An exploratory study of paediatric liver tumours and adjacent normal tissue. The project will seek to 1) identify differences in methylation between platinum treated and platinum naïve cases, and 2) investigate the epigenetic consequences of Beckwith-Wiedemann syndrome, which several of these children have. ","abstract":"An exploratory study of paediatric liver tumours and adjacent normal tissue. The project will seek to 1) identify differences in methylation between platinum treated and platinum naïve cases, and 2) investigate the epigenetic consequences of Beckwith-Wiedemann syndrome, which several of these children have. ","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008114","title":"Aberrant basal cell clonal dynamics shape early lung carcinogenesis","description":"Lung PCA - whole exome multiregion sequencing data from human preinvasive airway biopsies","abstract":"Lung PCA - whole exome multiregion sequencing data from human preinvasive airway biopsies","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-04-30T23:35:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008115","title":"Whole_Genome_Sequencing_OMELib__CML_","description":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification).","abstract":"The mutational landscape of haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA(primary template-directed amplification).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008116","title":"RNA_Seq_OMELib__CML_","description":"The transcriptional landscape of haematopoietic cells will be characterized by scRNA-sequencing. Libraries were created using the ResolveOME v2 protocol.","abstract":"The transcriptional landscape of haematopoietic cells will be characterized by scRNA-sequencing. Libraries were created using the ResolveOME v2 protocol.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008117","title":" Plasma MicroRNA Signatures of Aging","description":"Background. MicroRNAs are small non-coding RNAs that regulate gene expression post-transcriptionally and show differential expression in various tissues with aging phenotypes. Detectable in circulation, extracellular microRNAs reflect (patho)physiological processes and hold promise as biomarkers for healthy aging and age-related diseases. This study aimed to explore plasma extracellular microRNAs as biological aging indicator and their associations with health outcomes using population-level data.\n\nMethods. We quantified plasma expression levels of 2,083 extracellular microRNAs using targeted RNA-sequencing in 2,684 participants from the population-based Rotterdam Study cohort. The training and test sets included 1,930 participants from the advanced-aged initial and second subcohort (RS-I/RS-II; median age: 70.6), while the validation set comprised 754 participants from the middle-aged fourth subcohort (RS-IV; median age: 53.5). Based on 591 microRNAs well-expressed in plasma, we examined differential expression of microRNAs with chronological age, PhenoAge –a composite score of age and nine multi-system blood biomarkers–, the frailty index, and mortality. Next, elastic net models were employed to construct composite microRNA-based aging biomarkers predicting chronological age (mirAge), PhenoAge (mirPA), frailty index (mirFI), and mortality (mirMort). The association of these aging biomarkers with different age-related health outcomes was assessed using Cox Proportional Hazard, linear regression, and logistic regression models in the test and validation sets.\n\nResults. We identified 188 microRNAs differentially expressed with chronological age within the RS-I/RS-II advanced-aged population (ntraining=1158, ntest=772), of which 177 microRNAs (94.1%) were replicated in the middle-aged RS-IV subcohort (nvalidation=754). Moreover, 227 miRNAs showed robust associations with PhenoAge, 61 with FI, and 16 with ten-year mortality independent of chronological age. Subsequently, we constructed four plasma microRNA-based aging biomarkers: mirAge with 108, mirPA with 153, mirFI with 81, and mirMort with 50 miRNAs. Elevated scores on these microRNA-based aging biomarkers were associated with unfavorable health outcomes, including lower subjective physical functioning and self-reported health and increased mortality and frailty risk, but not with first- or multi-morbidity. Overall, larger effect estimates were observed for mirPA, mirFI, and mirMort compared to mirAge. \n\nConclusions. This study describes distinct plasma microRNA-aging signatures and introduces four microRNA-based aging biomarkers with potential to identify accelerated aging and age-related decline, providing insights into the intricate process of human aging.\n","abstract":"Background. MicroRNAs are small non-coding RNAs that regulate gene expression post-transcriptionally and show differential expression in various tissues with aging phenotypes. Detectable in circulation, extracellular microRNAs reflect (patho)physiological processes and hold promise as biomarkers for healthy aging and age-related diseases. This study aimed to explore plasma extracellular microRNAs as biological aging indicator and their associations with health outcomes using population-level data.\n\nMethods. We quantified plasma expression levels of 2,083 extracellular microRNAs using targeted RNA-sequencing in 2,684 participants from the population-based Rotterdam Study cohort. The training and test sets included 1,930 participants from the advanced-aged initial and second subcohort (RS-I/RS-II; median age: 70.6), while the validation set comprised 754 participants from the middle-aged fourth subcohort (RS-IV; median age: 53.5). Based on 591 microRNAs well-expressed in plasma, we examined differential expression of microRNAs with chronological age, PhenoAge –a composite score of age and nine multi-system blood biomarkers–, the frailty index, and mortality. Next, elastic net models were employed to construct composite microRNA-based aging biomarkers predicting chronological age (mirAge), PhenoAge (mirPA), frailty index (mirFI), and mortality (mirMort). The association of these aging biomarkers with different age-related health outcomes was assessed using Cox Proportional Hazard, linear regression, and logistic regression models in the test and validation sets.\n\nResults. We identified 188 microRNAs differentially expressed with chronological age within the RS-I/RS-II advanced-aged population (ntraining=1158, ntest=772), of which 177 microRNAs (94.1%) were replicated in the middle-aged RS-IV subcohort (nvalidation=754). Moreover, 227 miRNAs showed robust associations with PhenoAge, 61 with FI, and 16 with ten-year mortality independent of chronological age. Subsequently, we constructed four plasma microRNA-based aging biomarkers: mirAge with 108, mirPA with 153, mirFI with 81, and mirMort with 50 miRNAs. Elevated scores on these microRNA-based aging biomarkers were associated with unfavorable health outcomes, including lower subjective physical functioning and self-reported health and increased mortality and frailty risk, but not with first- or multi-morbidity. Overall, larger effect estimates were observed for mirPA, mirFI, and mirMort compared to mirAge. \n\nConclusions. This study describes distinct plasma microRNA-aging signatures and introduces four microRNA-based aging biomarkers with potential to identify accelerated aging and age-related decline, providing insights into the intricate process of human aging.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-01T11:51:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008118","title":"Raw bulk TCRseq data fromTIL and non-TIL expanded TRACERx samples in the manuscript Bulk TCRseq from TRACERx samples from 'Subclonal immune evasion in non-small cell lung cancer'  ","description":"Immune checkpoint blockade in non-small cell lung cancer (NSCLC) rarely leads to complete tumour remission, suggesting that tumours harbour subpopulations of cancer cells that can escape immune predation. However, while tumours consist of multiple genetically distinct clones, the extent to which separate tumour subclones differ intrinsically in their functional capacity for immune evasion remains largely unexplored. This has been challenging to address due to an inability to isolate and propagate individual tumour subclones from human cancers. Here, we leverage the multi-region TRACERx lung cancer evolution study to generate a patient-derived platform that allows the functional analysis of immune escape at single clone resolution. We generated libraries of &gt;20 separate NSCLC organoid lines per patient by isolating individual (clonal) organoids established from multiple spatially separated tumour regions. Each organoid subline was co-cultured with autologous tumour infiltrating lymphocytes (TIL) to evaluate their capacity to elicit a T cell response. Organoid lines derived from separate tumour regions, or from single clones within individual regions, differ vastly in their capacity to elicit a T cell response, showing the coexistence of intrinsically immune evading (‘cold) and non-evading (‘hot) clones in the same primary tumour. Organoid lines escaping T cell recognition represent genetically and transcriptionally unique subclones with a distinct evolutionary history, showing that evolutionary sculpting of subclonal diversity can have functional consequences for anti-tumour immunity. Notably, the identification of immune-evasive subclones would not have been possible using computational approaches alone, highlighting the unique value of functional co-culture platforms. This patient-derived functional co-culture platform reveals that tumour evolution can give rise to distinct cancer clones with intrinsic differences in immune evasion capacity and provides an approach to prospectively identify, isolate and characterise immune evading subclones from patients with cancer.","abstract":"Immune checkpoint blockade in non-small cell lung cancer (NSCLC) rarely leads to complete tumour remission, suggesting that tumours harbour subpopulations of cancer cells that can escape immune predation. However, while tumours consist of multiple genetically distinct clones, the extent to which separate tumour subclones differ intrinsically in their functional capacity for immune evasion remains largely unexplored. This has been challenging to address due to an inability to isolate and propagate individual tumour subclones from human cancers. Here, we leverage the multi-region TRACERx lung cancer evolution study to generate a patient-derived platform that allows the functional analysis of immune escape at single clone resolution. We generated libraries of &gt;20 separate NSCLC organoid lines per patient by isolating individual (clonal) organoids established from multiple spatially separated tumour regions. Each organoid subline was co-cultured with autologous tumour infiltrating lymphocytes (TIL) to evaluate their capacity to elicit a T cell response. Organoid lines derived from separate tumour regions, or from single clones within individual regions, differ vastly in their capacity to elicit a T cell response, showing the coexistence of intrinsically immune evading (‘cold) and non-evading (‘hot) clones in the same primary tumour. Organoid lines escaping T cell recognition represent genetically and transcriptionally unique subclones with a distinct evolutionary history, showing that evolutionary sculpting of subclonal diversity can have functional consequences for anti-tumour immunity. Notably, the identification of immune-evasive subclones would not have been possible using computational approaches alone, highlighting the unique value of functional co-culture platforms. This patient-derived functional co-culture platform reveals that tumour evolution can give rise to distinct cancer clones with intrinsic differences in immune evasion capacity and provides an approach to prospectively identify, isolate and characterise immune evading subclones from patients with cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-02T09:20:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008119","title":"Inquiring the potential of donor derived CD19-CAR TSCM to treat B-cell malignancies.","description":"Relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) is associated with poor survival in advanced B-cell malignancies. Donor-derived CD19-CAR T cells offer the potential for durable remissions but are limited by poor engraftment, expansion, and persistence. We report results from a sequential Phase 1 study (NCT01087294) in which patients with B-cell malignancies relapsed after alloHSCT received either donor-derived standard or stem cell memory T (TSCM)-enriched CD19-CAR T cells without lymphodepletion preconditioning. CAR TSCM cells exhibited delayed but superior expansion and persistence, leading to higher complete remission rates (45% vs. 10%) for doses &lt; 3×108 CAR T cells. Despite their potency, CAR TSCM cells induced milder cytokine-mediated toxicities, driven by IFN-γ rather than IL-6, as observed in standard CAR T cell recipients. While both T cell products differentiated into effectors, only CAR TSCM cells robustly reconstituted the stem-like compartment. Longitudinal clonal-tracking revealed CAR TSCM cells were maintained by clonal succession, whereas standard CAR T cells persisted through maintenance or attrition of early-expanded clones. Unlike standard CAR T cells, CAR TSCM treatment failure was primarily due to tumor- and host-related factors rather than intrinsic T cell defects. These findings establish TSCM cells as a safe and highly effective CAR T cell platform.","abstract":"Relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) is associated with poor survival in advanced B-cell malignancies. Donor-derived CD19-CAR T cells offer the potential for durable remissions but are limited by poor engraftment, expansion, and persistence. We report results from a sequential Phase 1 study (NCT01087294) in which patients with B-cell malignancies relapsed after alloHSCT received either donor-derived standard or stem cell memory T (TSCM)-enriched CD19-CAR T cells without lymphodepletion preconditioning. CAR TSCM cells exhibited delayed but superior expansion and persistence, leading to higher complete remission rates (45% vs. 10%) for doses &lt; 3×108 CAR T cells. Despite their potency, CAR TSCM cells induced milder cytokine-mediated toxicities, driven by IFN-γ rather than IL-6, as observed in standard CAR T cell recipients. While both T cell products differentiated into effectors, only CAR TSCM cells robustly reconstituted the stem-like compartment. Longitudinal clonal-tracking revealed CAR TSCM cells were maintained by clonal succession, whereas standard CAR T cells persisted through maintenance or attrition of early-expanded clones. Unlike standard CAR T cells, CAR TSCM treatment failure was primarily due to tumor- and host-related factors rather than intrinsic T cell defects. These findings establish TSCM cells as a safe and highly effective CAR T cell platform.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-05T10:33:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008120","title":"TEST","description":"TEST","abstract":"TEST","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008121","title":"H3K4me3, IgG, and Input ChIP-seq in overexpression of pLV Control, CS-FL and CS-ΔEx4 in SW1116 cells.","description":"none","abstract":"none","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-06T13:53:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008122","title":"IDH-wildtype untreated human glioblatoma samples (GB-UK cohort), published in Noorani & Haughey et al 2025.","description":"Extrachromosomal DNA (ecDNA) oncogene amplification is associated with treatment resistance and shorter survival in cancer. Currently, the spatial dynamics of ecDNA, and their evolutionary impact, are poorly understood. Here, we investigate the spatiotemporal evolution of ecDNA by integrating computational modeling with samples from 94 treatment-naive human IDH wild-type glioblastoma patients. Random ecDNA segregation combined with ecDNA-conferred fitness advantages induce distinct spatial ecDNA copy number patterns which depend on ecDNA oncogenic makeup. EGFR-ecDNAs often reach high copy numbers and confer strong fitness advantages. In contrast, PDGFRA-ecDNAs reach lower copy numbers and confer weaker fitness advantages. EGFR structural variants occur exclusively on ecDNA, arise from and are intermixed with wild-type EGFR-ecDNAs. Computational modeling suggests wild-type and variant EGFR-ecDNAs often accumulate before clonal expansion. Using a genetically engineered mouse model, we confirm that the accumulation of oncogenic ecDNA prior to clonal expansion under strong positive selection is observable both in vivo and in vitro in mouse neural stem cells. Intermixed wild-type and variant ecDNAs remain prevalent at diagnosis, as less fit wild-type ecDNAs hitchhike on strongly selected variant EGFR-ecDNAs. A dN/dS analysis in the Genomics England cohort further suggests positive selection of variants on EGFR-ecDNAs but not PDGFRA-ecDNAs in glioblastoma. Overall, our results suggest ecDNA oncogenic makeup determines unique evolutionary trajectories in glioblastoma. New concepts like ecDNA tumor clonality, ecDNA heteroplasmy and multi-species ecDNAs require a refined evolutionary interpretation of genomic data in a large subset of glioblastoma patients and likely other solid cancers.","abstract":"Extrachromosomal DNA (ecDNA) oncogene amplification is associated with treatment resistance and shorter survival in cancer. Currently, the spatial dynamics of ecDNA, and their evolutionary impact, are poorly understood. Here, we investigate the spatiotemporal evolution of ecDNA by integrating computational modeling with samples from 94 treatment-naive human IDH wild-type glioblastoma patients. Random ecDNA segregation combined with ecDNA-conferred fitness advantages induce distinct spatial ecDNA copy number patterns which depend on ecDNA oncogenic makeup. EGFR-ecDNAs often reach high copy numbers and confer strong fitness advantages. In contrast, PDGFRA-ecDNAs reach lower copy numbers and confer weaker fitness advantages. EGFR structural variants occur exclusively on ecDNA, arise from and are intermixed with wild-type EGFR-ecDNAs. Computational modeling suggests wild-type and variant EGFR-ecDNAs often accumulate before clonal expansion. Using a genetically engineered mouse model, we confirm that the accumulation of oncogenic ecDNA prior to clonal expansion under strong positive selection is observable both in vivo and in vitro in mouse neural stem cells. Intermixed wild-type and variant ecDNAs remain prevalent at diagnosis, as less fit wild-type ecDNAs hitchhike on strongly selected variant EGFR-ecDNAs. A dN/dS analysis in the Genomics England cohort further suggests positive selection of variants on EGFR-ecDNAs but not PDGFRA-ecDNAs in glioblastoma. Overall, our results suggest ecDNA oncogenic makeup determines unique evolutionary trajectories in glioblastoma. New concepts like ecDNA tumor clonality, ecDNA heteroplasmy and multi-species ecDNAs require a refined evolutionary interpretation of genomic data in a large subset of glioblastoma patients and likely other solid cancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008123","title":"A cycling, progenitor-like cell population at the root of atypical teratoid rhabdoid tumor subtype differentiation trajectories","description":null,"abstract":"Atypical teratoid rhabdoid tumors (ATRTs), characterized by the loss of SMARCB1, are among the most lethal pediatric central nervous system (CNS) tumors. Three molecular subtypes have been identified, each defined by distinct molecular and clinical features. No subtype-specific treatments are available, highlighting the need to better understand inter- and intra-subtype heterogeneity. Here, we generated a single-nucleus transcriptome atlas of ATRTs, validated by single-cell ATAC-seq and spatial transcriptomics, to study subtype-specific differentiation trajectories. We identified brain progenitor-like expression profiles within unique subtype-specific differentiation lineages. A shared cycling, progenitor-like cell population, interspersed throughout tumors, was observed across all ATRT samples. Moreover, we demonstrate that subtype-specific differentiation trajectories can be induced pharmacologically in ATRT tumoroids directing tumor cells towards a non-proliferative, mature phenotype. Our study reveals that ATRT subtypes exhibit signaling trajectories mirroring normal fetal brain development, potentially enabling the development of maturation therapies tailored towards ATRTs.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-07T09:48:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008124","title":"Multidimensional, comprehensive longitudinal molecular profiling over a 20-year life-time history of a tumor guides personalized treatment and drives an exceptional outcome in a metastatic breast cancer patient ","description":"Precision oncology-protocols based on genomic-sequencing are entering clinical practice in metastatic breast cancer (mBC) delivering therapy-algorithms driven by the individual molecular biomarker-landscape. However, current approaches are largely confined to single tissue lesion-profiling omitting evolutionary drifts underlying treatment-failure and often display limited therapeutic options for targeting co-occurent tumor vulnerabilities. \nWithin the CATCH precision oncology platform, we present extensive multi-regional and sequential molecular profiling of one patient with initially HR+/HER- mBC spanning the entire disease continuum of approximately 20 years (14 years eBC + 6 years mBC) by inferring 6 tissue and &gt;50 blood-based liquid biopsy (LBx) time-points. Integrative tissue analyses, including routine-IHC and multi-omics profiling (whole-exome/-RNA-sequencing), captured several distinct biological entities and a subtype-switch from HR+/HER2- to TNBC, accompanied by persistence of a PIK3CA mutation (p.H1047Y). Newly emergent, pivotal actionable biomarkers (ERBB2 p.G776V) refined the formal TNBC-classification and informed consecutive complex combinatorial therapy-lines contributing to an extraordinary clinical outcome.\nTissue-based biomarker-guided therapy algorithms were complemented by a high-frequency multi-parametric LBx-workup -including tumormarker (TM), circulating tumor cells (CTC), and cell-free tumor DNA (ctDNA). Semi-quantitative LBx analyses largely displayed inter-assay concordance and even outperformed standard imaging in predicting treatment response. The LBx-landscape faithfully recapitulated clinically-relevant mutations identified in the tissue and  sub-clonal resistance mechanisms on ctDNA level. Sequential quantification of CTC-based HER2-expression highlighted the ongoing relevance of the ERBB2-axis. \nIn summary, the integrative N-of-1 picture -leveraging multidimensional orthogonal profiling in a mBC patient- provides a real-world proof-of-concept that intensified monitoring of the tumor dynamics can improve clinical decision-making and outcome. The multidisciplinary approach realizes the full potential of precision oncology to repurpose biomarker-driven therapies and outlines a next-generation personalized healthcare strategy for mBC to impact patient outcome. ","abstract":"Precision oncology-protocols based on genomic-sequencing are entering clinical practice in metastatic breast cancer (mBC) delivering therapy-algorithms driven by the individual molecular biomarker-landscape. However, current approaches are largely confined to single tissue lesion-profiling omitting evolutionary drifts underlying treatment-failure and often display limited therapeutic options for targeting co-occurent tumor vulnerabilities. \nWithin the CATCH precision oncology platform, we present extensive multi-regional and sequential molecular profiling of one patient with initially HR+/HER- mBC spanning the entire disease continuum of approximately 20 years (14 years eBC + 6 years mBC) by inferring 6 tissue and &gt;50 blood-based liquid biopsy (LBx) time-points. Integrative tissue analyses, including routine-IHC and multi-omics profiling (whole-exome/-RNA-sequencing), captured several distinct biological entities and a subtype-switch from HR+/HER2- to TNBC, accompanied by persistence of a PIK3CA mutation (p.H1047Y). Newly emergent, pivotal actionable biomarkers (ERBB2 p.G776V) refined the formal TNBC-classification and informed consecutive complex combinatorial therapy-lines contributing to an extraordinary clinical outcome.\nTissue-based biomarker-guided therapy algorithms were complemented by a high-frequency multi-parametric LBx-workup -including tumormarker (TM), circulating tumor cells (CTC), and cell-free tumor DNA (ctDNA). Semi-quantitative LBx analyses largely displayed inter-assay concordance and even outperformed standard imaging in predicting treatment response. The LBx-landscape faithfully recapitulated clinically-relevant mutations identified in the tissue and  sub-clonal resistance mechanisms on ctDNA level. Sequential quantification of CTC-based HER2-expression highlighted the ongoing relevance of the ERBB2-axis. \nIn summary, the integrative N-of-1 picture -leveraging multidimensional orthogonal profiling in a mBC patient- provides a real-world proof-of-concept that intensified monitoring of the tumor dynamics can improve clinical decision-making and outcome. The multidisciplinary approach realizes the full potential of precision oncology to repurpose biomarker-driven therapies and outlines a next-generation personalized healthcare strategy for mBC to impact patient outcome. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008125","title":"Sequencing data from a highly cost-effective cell-free DNA methylome test","description":"Plasma cell-free DNA (cfDNA), originating from multiple organs, holds significant potential for non-invasive diagnostics and prognostics. Current cfDNA methylation assays primarily focus on single clinical indications by targeting specific genomic loci. In contrast, comprehensive profiling of cfDNA methylome can enable simultaneous detection of multiple diseases by capturing organ-specific methylation signatures, thereby offering a holistic view of health, when disease etiology is unclear or when conventional biochemical diagnostics are unavailable. However, deep sequencing required for sensitive detection of methylation abnormalities remains prohibitively expensive, limiting widespread clinical use. To overcome this barrier, we developed MethylScan, a highly cost-effective approach for cfDNA methylome sequencing. We demonstrated its broad clinical utility in a cohort of 1,061 individuals across diverse applications, including multi-cancer detection in general population, liver cancer surveillance in high-risk individuals, liver disease classification, identification of organ abnormalities, and race prediction from cfDNA.","abstract":"Plasma cell-free DNA (cfDNA), originating from multiple organs, holds significant potential for non-invasive diagnostics and prognostics. Current cfDNA methylation assays primarily focus on single clinical indications by targeting specific genomic loci. In contrast, comprehensive profiling of cfDNA methylome can enable simultaneous detection of multiple diseases by capturing organ-specific methylation signatures, thereby offering a holistic view of health, when disease etiology is unclear or when conventional biochemical diagnostics are unavailable. However, deep sequencing required for sensitive detection of methylation abnormalities remains prohibitively expensive, limiting widespread clinical use. To overcome this barrier, we developed MethylScan, a highly cost-effective approach for cfDNA methylome sequencing. We demonstrated its broad clinical utility in a cohort of 1,061 individuals across diverse applications, including multi-cancer detection in general population, liver cancer surveillance in high-risk individuals, liver disease classification, identification of organ abnormalities, and race prediction from cfDNA.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-07T21:33:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008126","title":"IDH-wildtype untreated human glioblastoma samples (GB-UK cohort), published in Noorani & Haughey et al 2025.","description":"Extrachromosomal DNA (ecDNA) oncogene amplification is associated with treatment resistance and shorter survival in cancer. Currently, the spatial dynamics of ecDNA, and their evolutionary impact, are poorly understood. Here, we investigate the spatiotemporal evolution of ecDNA by integrating computational modeling with samples from 94 treatment-naive human IDH wild-type glioblastoma patients. Random ecDNA segregation combined with ecDNA-conferred fitness advantages induce distinct spatial ecDNA copy number patterns which depend on ecDNA oncogenic makeup. EGFR-ecDNAs often reach high copy numbers and confer strong fitness advantages. In contrast, PDGFRA-ecDNAs reach lower copy numbers and confer weaker fitness advantages. EGFR structural variants occur exclusively on ecDNA, arise from and are intermixed with wild-type EGFR-ecDNAs. Computational modeling suggests wild-type and variant EGFR-ecDNAs often accumulate before clonal expansion. Using a genetically engineered mouse model, we confirm that the accumulation of oncogenic ecDNA prior to clonal expansion under strong positive selection is observable both in vivo and in vitro in mouse neural stem cells. Intermixed wild-type and variant ecDNAs remain prevalent at diagnosis, as less fit wild-type ecDNAs hitchhike on strongly selected variant EGFR-ecDNAs. A dN/dS analysis in the Genomics England cohort further suggests positive selection of variants on EGFR-ecDNAs but not PDGFRA-ecDNAs in glioblastoma. Overall, our results suggest ecDNA oncogenic makeup determines unique evolutionary trajectories in glioblastoma. New concepts like ecDNA tumor clonality, ecDNA heteroplasmy and multi-species ecDNAs require a refined evolutionary interpretation of genomic data in a large subset of glioblastoma patients and likely other solid cancers.","abstract":"Extrachromosomal DNA (ecDNA) oncogene amplification is associated with treatment resistance and shorter survival in cancer. Currently, the spatial dynamics of ecDNA, and their evolutionary impact, are poorly understood. Here, we investigate the spatiotemporal evolution of ecDNA by integrating computational modeling with samples from 94 treatment-naive human IDH wild-type glioblastoma patients. Random ecDNA segregation combined with ecDNA-conferred fitness advantages induce distinct spatial ecDNA copy number patterns which depend on ecDNA oncogenic makeup. EGFR-ecDNAs often reach high copy numbers and confer strong fitness advantages. In contrast, PDGFRA-ecDNAs reach lower copy numbers and confer weaker fitness advantages. EGFR structural variants occur exclusively on ecDNA, arise from and are intermixed with wild-type EGFR-ecDNAs. Computational modeling suggests wild-type and variant EGFR-ecDNAs often accumulate before clonal expansion. Using a genetically engineered mouse model, we confirm that the accumulation of oncogenic ecDNA prior to clonal expansion under strong positive selection is observable both in vivo and in vitro in mouse neural stem cells. Intermixed wild-type and variant ecDNAs remain prevalent at diagnosis, as less fit wild-type ecDNAs hitchhike on strongly selected variant EGFR-ecDNAs. A dN/dS analysis in the Genomics England cohort further suggests positive selection of variants on EGFR-ecDNAs but not PDGFRA-ecDNAs in glioblastoma. Overall, our results suggest ecDNA oncogenic makeup determines unique evolutionary trajectories in glioblastoma. New concepts like ecDNA tumor clonality, ecDNA heteroplasmy and multi-species ecDNAs require a refined evolutionary interpretation of genomic data in a large subset of glioblastoma patients and likely other solid cancers.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-08-01T12:50:08.002999+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008127","title":"Sequencing data from MethylScan assay on plasma","description":"Machine learning models in biomedical research are often hindered by demographic imbalances in clinical datasets, leading to biased predictions that disadvantage minority populations. Existing bias correction methods face limitations in handling the heterogeneity of biomedical data and the complexity of demographic influences. Here, we present DeBias, a computational framework for mitigating demographic biases in high-dimensional biomedical datasets. DeBias eliminates bias-associated subspaces within the entire feature space using control samples and enables global bias correction across all features, effectively preserving disease-specific signals while minimizing demographic distortions. To demonstrate its effectiveness, we applied DeBias to cfDNA methylation data for cancer detection. It achieved a &gt;6-fold reduction in the number of features containing biases and outperformed existing methods in improving the cancer detection performance for minority populations. Our method represented a promising step toward developing machine learning models that are more accurate, reliable, and equitable for minority populations.","abstract":"Machine learning models in biomedical research are often hindered by demographic imbalances in clinical datasets, leading to biased predictions that disadvantage minority populations. Existing bias correction methods face limitations in handling the heterogeneity of biomedical data and the complexity of demographic influences. Here, we present DeBias, a computational framework for mitigating demographic biases in high-dimensional biomedical datasets. DeBias eliminates bias-associated subspaces within the entire feature space using control samples and enables global bias correction across all features, effectively preserving disease-specific signals while minimizing demographic distortions. To demonstrate its effectiveness, we applied DeBias to cfDNA methylation data for cancer detection. It achieved a &gt;6-fold reduction in the number of features containing biases and outperformed existing methods in improving the cancer detection performance for minority populations. Our method represented a promising step toward developing machine learning models that are more accurate, reliable, and equitable for minority populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-10T00:25:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008128","title":"Characterization of UV DNA damage in B-cell precursor acute lymphoblastic leukemia","description":null,"abstract":"We characterized B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients that present with the mutational signature SBS7a. We found clear subtype specificity, but presence of SBS7a did not seem linked to heterogeneity within subtypes. To further distinguish the incidence of SBS7a in pediatric cancer we analyzed a pan-cancer WGS cohort and identified frequent SBS7a in anaplastic large cell lymphomas. As SBS7a is commonly found in skin cancers and has been linked to UV-light induced DNA damage, we compared the features of UV-light induced DNA damage in skin cancer and SBS7a in ALL, and found high similarity. We found no defects in UV damage response pathways in SBS7a-positive samples, indicating no additional UV vulnerability. Additionally, transcriptomic data showed no differences between samples with and without SBS7a. Finally we looked into the moment of exposure to the source of SBS7a by deep sequencing of diagnosis-relapse pairs and single cell whole genome sequencing of diagnosis samples with high SBS7a.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-12T10:29:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008129","title":"Oesophageal_carcinoma_mutational_signature_in_South_African_patients","description":"We wish to perform WGS on oesophageal SCC tumour and blood samples from South African patients to attempt to identify any mutational signature which may link to environmental influences.","abstract":"We wish to perform WGS on oesophageal SCC tumour and blood samples from South African patients to attempt to identify any mutational signature which may link to environmental influences.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008130","title":"DERMATLAS__Rare_human_skin_tumours_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n      The cases in this cohort are a collection of different types of rare/infrequently-occurring skin tumours.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n      The cases in this cohort are a collection of different types of rare/infrequently-occurring skin tumours.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008131","title":"DERMATLAS__Rare_human_skin_tumours_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n      The cases in this cohort are a collection of different types of rare/infrequently-occurring skin tumours.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n      The cases in this cohort are a collection of different types of rare/infrequently-occurring skin tumours.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008132","title":"PMBCL IRF4 study","description":"This submission included the scRNA-seq samples included in the Somatic IRF4 mutations drive disease-defining hallmarks and thymic tropism in \nprimary mediastinal large B-cell lymphoma study","abstract":"This submission included the scRNA-seq samples included in the Somatic IRF4 mutations drive disease-defining hallmarks and thymic tropism in \nprimary mediastinal large B-cell lymphoma study","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008133","title":"A complex chromosomal rearrangement (CCR) was resolved at the nucleotide level by whole genome long read sequencing using PacBio sequencing platform.","description":"A complex chromosomal rearrangement (CCR) involving 7 chromosomes and 11 breakpoints was resolved at the nucleotide level by whole genome long read sequencing using PacBio sequencing platform.","abstract":"A complex chromosomal rearrangement (CCR) involving 7 chromosomes and 11 breakpoints was resolved at the nucleotide level by whole genome long read sequencing using PacBio sequencing platform.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-14T13:08:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008134","title":"The circulating cell-free DNA landscape in sepsis is dominated by impaired liver clearance","description":"Circulating cell-free DNA (cfDNA) is a promising molecular biomarker. However, its utility in severe infection remains poorly understood. Here, we isolated cfDNA from sepsis patients and controls, demonstrating a 41-fold increase in the amount of cfDNA in circulation during disease. We used sequencing to reconstruct cfDNA methylomes, fragmentation profiles, and nucleosome footprints across 58 samples. We observed no difference in cfDNA composition between patients and controls, challenging the idea that cfDNA increases due to higher immune cell death during sepsis. Instead, we suggest that liver dysfunction prevents efficient clearance of cfDNA during disease. This was supported by fragmentation and end-motif patterns, both of which showed evidence of cfDNA being exposed to circulating nucleases for a prolonged period, proportionally to the extent of liver dysfunction. Variation in cfDNA of megakaryocyte-erythroid progenitor origin was also a significant contributor in sepsis, increasing over time. Moreover, we showed that cfDNA retains nucleosome footprints with cell type-specific gene activity information. We developed a novel approach to study nucleosome phasing that successfully recovers tissue-specific signatures. By combining this with single-cell data, we demonstrated that sepsis patients with liver dysfunction have higher amounts of cfDNA derived from Kupffer cells and the liver parenchyma. In conclusion, we present the first high-throughput multi-modal study of cfDNA during sepsis, which will serve as a reference point for future studies on the role of this biomarker in critical illness.","abstract":"Circulating cell-free DNA (cfDNA) is a promising molecular biomarker. However, its utility in severe infection remains poorly understood. Here, we isolated cfDNA from sepsis patients and controls, demonstrating a 41-fold increase in the amount of cfDNA in circulation during disease. We used sequencing to reconstruct cfDNA methylomes, fragmentation profiles, and nucleosome footprints across 58 samples. We observed no difference in cfDNA composition between patients and controls, challenging the idea that cfDNA increases due to higher immune cell death during sepsis. Instead, we suggest that liver dysfunction prevents efficient clearance of cfDNA during disease. This was supported by fragmentation and end-motif patterns, both of which showed evidence of cfDNA being exposed to circulating nucleases for a prolonged period, proportionally to the extent of liver dysfunction. Variation in cfDNA of megakaryocyte-erythroid progenitor origin was also a significant contributor in sepsis, increasing over time. Moreover, we showed that cfDNA retains nucleosome footprints with cell type-specific gene activity information. We developed a novel approach to study nucleosome phasing that successfully recovers tissue-specific signatures. By combining this with single-cell data, we demonstrated that sepsis patients with liver dysfunction have higher amounts of cfDNA derived from Kupffer cells and the liver parenchyma. In conclusion, we present the first high-throughput multi-modal study of cfDNA during sepsis, which will serve as a reference point for future studies on the role of this biomarker in critical illness.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008135","title":"NanoSeq__LCM____Characterising_smoking_effects_on_the_AhR_pathway","description":"The aim of this study is to investigate the mechanisms of the increased mutation burden induced by smoking related mutagens (e.g. Benzo-a-pyrene). Here we use trachea biopsies from patients with distinct smoking status to dissect subpopulation marked by KRT5 and KRT13 and assess the sensitivity of different cells against smoking related mutagenesis. ","abstract":"The aim of this study is to investigate the mechanisms of the increased mutation burden induced by smoking related mutagens (e.g. Benzo-a-pyrene). Here we use trachea biopsies from patients with distinct smoking status to dissect subpopulation marked by KRT5 and KRT13 and assess the sensitivity of different cells against smoking related mutagenesis. ","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008136","title":"RENanoSeq____Studying_the_differences_between_airway_low__and_high__mutant_airway_basal_cells","description":"The aim of this study is to further profiling a subset of human airway basal cells that are intrinsically protected against tobacco smoke induced mutagenesis and how they respond to mutagen treatment. This dataset will include the RENanoSeq data generated from BaP treated high- and low-mutant basal cell colonies. ","abstract":"The aim of this study is to further profiling a subset of human airway basal cells that are intrinsically protected against tobacco smoke induced mutagenesis and how they respond to mutagen treatment. This dataset will include the RENanoSeq data generated from BaP treated high- and low-mutant basal cell colonies.   ","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008137","title":"RNASeq____Studying_the_differences_between_airway_low__and_high__mutant_airway_basal_cells","description":"The aim of this study is to further profiling a subset of human airway basal cells that are intrinsically protected against tobacco smoke induced mutagenesis and how they respond to mutagen treatment. This dataset will include the RNASeq data generated from BaP treated high- and low-mutant basal cell colonies. ","abstract":"The aim of this study is to further profiling a subset of human airway basal cells that are intrinsically protected against tobacco smoke induced mutagenesis and how they respond to mutagen treatment. This dataset will include the RNASeq data generated from BaP treated high- and low-mutant basal cell colonies. ","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008138","title":"Targeted_Determining_the_mutation_burden_in_non_invasive_lung_samples","description":"The aim of this study is to investigate the mutational landscape in non-invasive samples from human upper airway. Targeted NanoSeq data will be generated using multi-regional biopsies from patients going through head and neck cancer screening. ","abstract":"The aim of this study is to investigate the mutational landscape in non-invasive samples from human upper airway. Targeted NanoSeq data will be generated using multi-regional biopsies from patients going through head and neck cancer screening.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008139","title":"Clonal B cells in MM and AL","description":"We performed whole exome sequencing (WES) on highly-purified MM and AL samples to define in which B-cell development stage the driver genetic alterations are present. ","abstract":"We performed whole exome sequencing (WES) on highly-purified MM and AL samples to define in which B-cell development stage the driver genetic alterations are present. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008140","title":"Selective targeting of TBXT with DARPins identifies regulatory networks and therapeutic vulnerabilities in chordoma","description":"The embryonic transcription factor TBXT (brachyury) drives chordoma, a spinal neoplasm without effective drug therapies. TBXT’s regulatory network is poorly understood, and strategies to disrupt its activity for therapeutic purposes are lacking. We developed designed ankyrin repeat proteins that block TBXT-DNA binding (T-DARPins). In chordoma cells, T-DARPins reduced cell cycle progression, spheroid formation, and tumor growth in mice and induced signs of senescence and differentiation. Transcriptomic and proteomic analyses identified gene networks involved in cell cycle regulation, embryonic cell identity, and interferon response and revealed features of regulome components, such as druggability for future translational studies and the fine-tuning of TBXT downstream effectors through IGFBP3. Finally, we found high interferon signaling in chordoma cell lines and patient tumors, which was promoted by TBXT and associated with sensitivity to JAK2 inhibitors. These findings demonstrate the potential of DARPins for probing nuclear proteins to understand the regulatory networks of transcription factor-driven cancers, including entry points for therapies that warrant testing in patients.","abstract":"The embryonic transcription factor TBXT (brachyury) drives chordoma, a spinal neoplasm without effective drug therapies. TBXT’s regulatory network is poorly understood, and strategies to disrupt its activity for therapeutic purposes are lacking. We developed designed ankyrin repeat proteins that block TBXT-DNA binding (T-DARPins). In chordoma cells, T-DARPins reduced cell cycle progression, spheroid formation, and tumor growth in mice and induced signs of senescence and differentiation. Transcriptomic and proteomic analyses identified gene networks involved in cell cycle regulation, embryonic cell identity, and interferon response and revealed features of regulome components, such as druggability for future translational studies and the fine-tuning of TBXT downstream effectors through IGFBP3. Finally, we found high interferon signaling in chordoma cell lines and patient tumors, which was promoted by TBXT and associated with sensitivity to JAK2 inhibitors. These findings demonstrate the potential of DARPins for probing nuclear proteins to understand the regulatory networks of transcription factor-driven cancers, including entry points for therapies that warrant testing in patients.","study_type":"Other","pubmed_ids":[40901948],"external_links":null,"is_released":true,"released_date":"2025-05-16T13:12:47+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008141","title":"High-throughput single-cell multiome of schizophrenia risk genes in hiPSC-derived NPCs and induced neurons using scifiRNA-seq & scifiATAC-seq","description":"High-throughput single-cell RNA-seq libraries (scifi-RNA-seq) and ATAC-seq libraries (scifi-ATAC-seq) following the knockdown of 65 schizophrenia-linked genes in hiPSC-derived NPCs and induced neurons. gRNA enrichment libraries were constructed from full-length cDNA (scifiRNA-seq) as described in the attached protocol, using a hemi-nested PCR approach.    Datasets named H5FWFDMXY_NPC_scifi_RT_001-024.* and H5FWFDMXY_Neuron_scifi_RT_001-024.* are the demultiplexed RNA single-cell RNA-seq.  Datasets connected to GBY49_Neuron_gRNA_enrichment and  GBY49_NPC_gRNA_enrichment libraries correspond gRNA enrichment and assignment of single cells to gRNA perturbations, with the barcode (potentially as reverse complement) indicated in the file name.   The 2 single-cell ATAC-seq libraires scifiATAC_scCRISPRi_Neuron and scifiATAC_scCRISPRi_NPC have been sequenced twice and are provided as 4 mulitplexed datasets which can be demuliplexed using the following barcodes: scCRISPRi_scifiATAC_001:ACAGGCTTCGT; scCRISPRi_scifiATAC_002:CTGGCAACGTA; scCRISPRi_scifiATAC_003:ATAAGTTAATT; scCRISPRi_scifiATAC_004:CCCATACCGAG; scCRISPRi_scifiATAC_005:AATTCACACGA; scCRISPRi_scifiATAC_006:GAACTAATTAT; scCRISPRi_scifiATAC_007:AGGAATTAGCC; scCRISPRi_scifiATAC_008:CACGACCTTCT; scCRISPRi_scifiATAC_009:ACCCCCTCACG; scCRISPRi_scifiATAC_010:CCTTTAGCCTA; scCRISPRi_scifiATAC_011:GAAGCCACTTC; scCRISPRi_scifiATAC_012:CGCTATGCGAT; scCRISPRi_scifiATAC_013:CTGGCTCGCCG; scCRISPRi_scifiATAC_014:CGTTTTCAAAT; scCRISPRi_scifiATAC_015:TCCAGAAAGGG; scCRISPRi_scifiATAC_016:CGCTGCAGTCA; scCRISPRi_scifiATAC_017:AACTTGATCGT; scCRISPRi_scifiATAC_018:GTCAGCATTTC; scCRISPRi_scifiATAC_019:CTTCAGGTAGC; scCRISPRi_scifiATAC_020:GTGTAGTTCCT; scCRISPRi_scifiATAC_021:TGACCGGCCGA; scCRISPRi_scifiATAC_022:ACGCTGGAAAA; scCRISPRi_scifiATAC_023:CGGCTACGATT; scCRISPRi_scifiATAC_024:TCGTAGTTTAC","abstract":"genetic modification design","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008142","title":"Single-cell multiome (RNA-seq & ATAC-seq) libraries constructed with the 10x Single Cell ATAC + Gene Expression kit following differentiation of hiPSCs to NPCs and induced neurons","description":"single-cell multiome (RNA-seq &amp; ATAC-seq) libraries constructed with the 10x Single Cell ATAC + Gene Expression kit following differentiation of hiPSCs to NPCs and induced neurons following CRISPRi of SOX5, SATB2, and SETD1A. Guide RNA identities were recovered through targeted amplification of the CROP-seq vector-derived transcript.","abstract":"genetic modification design","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008143","title":"Single-cell multiome over the course of in vitro NGN2-driven differentiation of hiPSCs to induced neurons using the commercial 10x Single Cell ATAC + Gene Expression workflow","description":"10X single-cell multiome (ATAC-seq and RNA-seq) libraries constructed with the 10x Singlle Cell ATAC + Gene Expression kit over the course of NGN2-driven differentiation of hiPSCs to induced neurons","abstract":"development or differentiation design","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008144","title":"Single-cell chromatin accessibility profiling of hiPSC-derived neurons following the 10x Single Cell ATAC kit","description":"Human iPSCs were differentiated via ectopic expression of NGN2 and scATAC-seq libraries prepared using the 10x Single Cell ATAC kit. This study was generated for a comparison with the single cell ATAC data from EGAS00001008141 ","abstract":"development or differentiation design","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008145","title":"Nala TAS-LRS PGx Study","description":"A study validating the use of TAS-LRS for clinical PGx reporting.","abstract":"Pharmacogenomics (PGx) testing improves medication safety and efficacy by identifying genetic variants that affect drug response. \n      However, current technologies often fail to resolve complex loci, detect structural variants, or phase alleles accurately. \n      Here, we present an end-to-end PGx workflow based on Targeted Adaptive Sampling-Long Read Sequencing (TAS-LRS), integrating a streamlined laboratory protocol with a bioinformatics pipeline that includes a novel CYP2D6 caller. \n      Using 1,000 ng of DNA and three-sample multiplexing on a single PromethION flow cell, the assay achieves consistent on-target (25x) and off-target (3x) coverage, enabling accurate, haplotype-resolved testing of 35 pharmacogenes alongside genome-wide genotyping from off-target reads. \n      We further developed the workflow into a clinically ready service and validated its performance across 17 reference and clinical samples. The assay demonstrated high concordance for small variants (99.9%) and structural variants (&gt;95%), with phased diplotypes and metabolizer phenotypes reaching 97.7% and 98.0% concordance, respectively. \n      Improved calls were observed in 12 genes due to enhanced genotyping, phasing, or novel allele detection. In addition, off-target reads supported accurate genome-wide imputation, comparable to short-read sequencing and superior to microarrays. \n      These results establish the feasibility of long-read sequencing for clinical PGx testing and position TAS-LRS as a scalable solution combining both targeted and genome-wide utility.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008146","title":"This study aimed to identify the genes that contributed to male infertility by whole exome sequencing of duo/trios in the Indian cohort.","description":"The study aimed to identify the genetic architecture of idiopathic male infertility patients in India. Patients were initially screened for aneuploidies and microdeletions using chromosomal G-banding karyotyping (at 500 band resolution) and Yq microdeletion by multiplex PCR. Whole exome sequencing was performed on germline DNA from 40 idiopathic male infertility patients and their parent(s). Target enrichment was performed using the Twist Biosciences Human Core Exome capture kit. Pooled libraries were sequenced on an Illumina NovaSeq X Plus sequencing platform at an average coverage of &gt;80-100x.","abstract":"The study aimed to identify the genetic architecture of idiopathic male infertility patients in India. Patients were initially screened for aneuploidies and microdeletions using chromosomal G-banding karyotyping (at 500 band resolution) and Yq microdeletion by multiplex PCR. Whole exome sequencing was performed on germline DNA from 40 idiopathic male infertility patients and their parent(s). Target enrichment was performed using the Twist Biosciences Human Core Exome capture kit. Pooled libraries were sequenced on an Illumina NovaSeq X Plus sequencing platform at an average coverage of &gt;80-100x.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008147","title":"Structural Variation in 1,019 Diverse Humans based on Long-Read Sequencing","description":"Long-read sequencing data of 1,019 humans covering 26 populations from the 1000 Genomes Project. Alignments are based on the T2T-CHM13 v2.0 reference  (T2T-CHM13 + chrY) with PARs on chrY hard masked to N and mitochondrion replaced with rCRS.","abstract":"Long-read sequencing data of 1,019 humans covering 26 populations from the 1000 Genomes Project. Alignments are based on the T2T-CHM13 v2.0 reference  (T2T-CHM13 + chrY) with PARs on chrY hard masked to N and mitochondrion replaced with rCRS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008148","title":"DERMATLAS__Kaposiform_hemangioendothelioma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Kaposiform hemangioendotheliomas.","abstract":" Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Kaposiform hemangioendotheliomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008149","title":"DERMATLAS__Kaposiform_hemangioendothelioma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Kaposiform hemangioendotheliomas.","abstract":" Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Kaposiform hemangioendotheliomas.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008150","title":"PDX_models_from_Latin_America_RNAseq","description":"Acral melanoma (AM) is a subtype of cutaneous melanoma that occurs on glabrous skin of the hands and feet (palms, soles and nail apparatus) and which is relatively more common in non-European descent populations such as those of Latin America. Compared to other subtypes, it is poorly studied and experimental models that faithfully reproduce human AM features are urgently needed. We report the generation and preliminary characterisation of a collection of patient-derived xenografts of acral melanomas (AM-PDX) from Latin-American patients. PDX came from Brazilian and Mexican patients cared for at the Instituto Nacional de Câncer (INCA) and the Instituto Nacional de Cancerologia (INCan). The majority of the samples are acral lentiginous melanomas, ulcerated, with &gt; 4mm Breslow depth and &gt; 2 mitosis / mm2. Samples were mechanically fragmented and subcutaneously implanted in NSG mice and then collected for molecular analysis. ","abstract":"Acral melanoma (AM) is a subtype of cutaneous melanoma that occurs on glabrous skin of the hands and feet (palms, soles and nail apparatus) and which is relatively more common in non-European descent populations such as those of Latin America. Compared to other subtypes, it is poorly studied and experimental models that faithfully reproduce human AM features are urgently needed. We report the generation and preliminary characterisation of a collection of patient-derived xenografts of acral melanomas (AM-PDX) from Latin-American patients. PDX came from Brazilian and Mexican patients cared for at the Instituto Nacional de Câncer (INCA) and the Instituto Nacional de Cancerologia (INCan). The majority of the samples are acral lentiginous melanomas, ulcerated, with &gt; 4mm Breslow depth and &gt; 2 mitosis / mm2. Samples were mechanically fragmented and subcutaneously implanted in NSG mice and then collected for molecular analysis. ","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-19T14:02:38+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008151","title":"Data generated as part of the study 'Single-cell mapping of regulatory DNA:Protein interactions.'","description":"Gene expression is coordinated by a multitude of transcription factors (TFs), whose binding to the genome is directed through multiple interconnected epigenetic signals, including chromatin accessibility and histone modifications. These complex networks have been shown to be disrupted during aging, disease, and cancer. However, profiling these networks across diverse cell types and states has been limited due to the technical constraints of existing methods for mapping DNA:Protein interactions in single cells. As a result, a critical gap remains in understanding where TFs or other chromatin remodelers bind to DNA and how these interactions are perturbed in pathological contexts. To address this challenge, we developed a transformative single-cell immuno-tethering DNA:Protein mapping technology. By coupling a species-specific antibody-binding nanobody to a cytosine base editing enzyme, this approach enables profiling of even weak or transient factor binding to DNA, a task that was previously unachievable in single cells. Thus, our Docking &amp; Deamination followed by sequencing (D&amp;D-seq) technique induces cytosine-to-uracil edits in genomic regions bound by the target protein, offering a novel means to capture DNA:Protein interactions with unprecedented resolution. Importantly, this technique can be seamlessly incorporated into common single-cell multiomics workflows, enabling multimodal analysis of gene regulation in single cells. In this study, we used ATAC-seq and scATAC-seq to define open chromatin regions as a functional readout for transcription factors activity.\nWe tested the ability of D&amp;D-seq to record TF binding both in bulk and at the single-cell level by profiling CTCF and GATA family members, obtaining high specificity and efficiency, with clear identification of TF footprint and signal retention in the targeted cell subpopulations. Furthermore, the deamination reaction showed minimal off-target activity, with high concordance to bulk ChIP-seq reference data. Applied to primary human peripheral blood mononuclear cells (PBMCs), D&amp;D-seq successfully identified CTCF binding sites and enabled integration with advanced machine-learning algorithms for predicting 3D chromatin structure. Furthermore, we integrated D&amp;D-seq with single-cell genotyping to assess the impact of IDH2 mutations on CTCF binding in a human clonal hematopoiesis sample, uncovering altered binding and chromatin co-accessibility patterns in mutant cells. Altogether, D&amp;D-seq represents an important technological advance enabling the direct mapping of TF or chromatin remodeler binding to the DNA in primary human samples, opening new avenues for understanding chromatin and transcriptional regulation in health and disease.","abstract":"Gene expression is coordinated by a multitude of transcription factors (TFs), whose binding to the genome is directed through multiple interconnected epigenetic signals, including chromatin accessibility and histone modifications. These complex networks have been shown to be disrupted during aging, disease, and cancer. However, profiling these networks across diverse cell types and states has been limited due to the technical constraints of existing methods for mapping DNA:Protein interactions in single cells. As a result, a critical gap remains in understanding where TFs or other chromatin remodelers bind to DNA and how these interactions are perturbed in pathological contexts. To address this challenge, we developed a transformative single-cell immuno-tethering DNA:Protein mapping technology. By coupling a species-specific antibody-binding nanobody to a cytosine base editing enzyme, this approach enables profiling of even weak or transient factor binding to DNA, a task that was previously unachievable in single cells. Thus, our Docking &amp; Deamination followed by sequencing (D&amp;D-seq) technique induces cytosine-to-uracil edits in genomic regions bound by the target protein, offering a novel means to capture DNA:Protein interactions with unprecedented resolution. Importantly, this technique can be seamlessly incorporated into common single-cell multiomics workflows, enabling multimodal analysis of gene regulation in single cells. In this study, we used ATAC-seq and scATAC-seq to define open chromatin regions as a functional readout for transcription factors activity.\nWe tested the ability of D&amp;D-seq to record TF binding both in bulk and at the single-cell level by profiling CTCF and GATA family members, obtaining high specificity and efficiency, with clear identification of TF footprint and signal retention in the targeted cell subpopulations. Furthermore, the deamination reaction showed minimal off-target activity, with high concordance to bulk ChIP-seq reference data. Applied to primary human peripheral blood mononuclear cells (PBMCs), D&amp;D-seq successfully identified CTCF binding sites and enabled integration with advanced machine-learning algorithms for predicting 3D chromatin structure. Furthermore, we integrated D&amp;D-seq with single-cell genotyping to assess the impact of IDH2 mutations on CTCF binding in a human clonal hematopoiesis sample, uncovering altered binding and chromatin co-accessibility patterns in mutant cells. Altogether, D&amp;D-seq represents an important technological advance enabling the direct mapping of TF or chromatin remodeler binding to the DNA in primary human samples, opening new avenues for understanding chromatin and transcriptional regulation in health and disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008152","title":"Idiopathic Scoliosis (SNP-array & WES study)","description":"This study aimed to investigate the genetic basis of severe idiopathic scoliosis (IS) using whole exome sequencing (WES) and SNP array methods. We intended to identify structural and point genetic variations contributing to the development of IS. By analyzing intraoperatively collected articular processes (AP) and blood (BL) samples from 70 unrelated individuals with IS, we sought to uncover pathogenic copy number variants (CNVs), regions of homozygosity (ROH), and single-nucleotide variants (SNVs) linked to the condition.\n\nEGAD00001015758","abstract":"This study aimed to investigate the genetic basis of severe idiopathic scoliosis (IS) using whole exome sequencing (WES) and SNP array methods. We intended to identify structural and point genetic variations contributing to the development of IS. By analyzing intraoperatively collected articular processes (AP) and blood (BL) samples from 70 unrelated individuals with IS, we sought to uncover pathogenic copy number variants (CNVs), regions of homozygosity (ROH), and single-nucleotide variants (SNVs) linked to the condition.\n\nEGAD00001015758","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008153","title":"Methylation Biomarkers can Distinguish Pleural Mesothelioma from Healthy Pleura and other Pleural Pathologies","description":"Pleural mesothelioma (PM) is a rare cancer type. This study developed a methylation-based biomarker assay to distinguish PM from healthy pleura and other pleural conditions. By analyzing methylation data, 744 hypermethylated CpG sites specific to PM were identified and validated with high accuracy. Using the bisulfite-free IMPRESS technique, the assay was further validated in a diverse cohort, showing strong performance in distinguishing tumoral from non-tumoral samples and PM from pleural metastases. These findings support the assay’s potential as a robust diagnostic tool for PM.","abstract":"Pleural mesothelioma (PM) is a rare cancer type. This study developed a methylation-based biomarker assay to distinguish PM from healthy pleura and other pleural conditions. By analyzing methylation data, 744 hypermethylated CpG sites specific to PM were identified and validated with high accuracy. Using the bisulfite-free IMPRESS technique, the assay was further validated in a diverse cohort, showing strong performance in distinguishing tumoral from non-tumoral samples and PM from pleural metastases. These findings support the assay’s potential as a robust diagnostic tool for PM.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008154","title":"Tumor-associated neutrophil 1 precursors impair homologous DNA repair and promote sensitivity to PARP-inhibition","description":"Tumor evolution is one of the major mechanisms responsible for acquiring therapy resistant and more aggressive cancer clones. Whether the tumor microenvironment through immune-mediated mechanisms might promote the development of more aggressive cancer types is crucial for the identification of additional therapeutical opportunities. Here, we identify a subset of tumor-associated neutrophils, defined as tumor-associated neutrophil precursors (PreNeu). These PreNeu are enriched in highly proliferative hormone-dependent breast cancers and impair DNA repair capacity","abstract":"Tumor evolution is one of the major mechanisms responsible for acquiring therapy resistant and more aggressive cancer clones. Whether the tumor microenvironment through immune-mediated mechanisms might promote the development of more aggressive cancer types is crucial for the identification of additional therapeutical opportunities. Here, we identify a subset of tumor-associated neutrophils, defined as tumor-associated neutrophil precursors (PreNeu). These PreNeu are enriched in highly proliferative hormone-dependent breast cancers and impair DNA repair capacity","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008155","title":"Cross-species Comparison Reveals Therapeutic Vulnerabilities Halting Glioblastoma Progression","description":"The growth of a tumor is tightly linked to the distribution of its cells\nalong a continuum of activation states. Here, we systematically\ndecode the activation state architecture (ASA) in a glioblastoma (GBM)\npatient cohort through comparison to adult murine neural stem cells.\nModelling of these data forecast how tumor cells organize to sustain\ngrowth and identifies rate of activation as the main predictor of\ngrowth. Accordingly, patients with a higher quiescence fraction exhibit\nimproved outcomes. Further, DNA methylation arrays enable ASA-\nrelated patient stratification. Comparison of healthy and malignant\ngene expression dynamics reveals dysregulation of the Wnt-\nantagonist SFRP1 at the quiescence to activation transition. SFRP1\noverexpression renders GBM quiescent and increases overall survival\nof tumor-bearing mice. Surprisingly, it does so through\nreprogramming the tumor’s stem-like methylome into an astrocyte-\nlike one. Our findings offer a framework for patient stratification with\nprognostic value, biomarker identification, and therapeutic avenues to\nhalt GBM progression.","abstract":"The growth of a tumor is tightly linked to the distribution of its cells\nalong a continuum of activation states. Here, we systematically\ndecode the activation state architecture (ASA) in a glioblastoma (GBM)\npatient cohort through comparison to adult murine neural stem cells.\nModelling of these data forecast how tumor cells organize to sustain\ngrowth and identifies rate of activation as the main predictor of\ngrowth. Accordingly, patients with a higher quiescence fraction exhibit\nimproved outcomes. Further, DNA methylation arrays enable ASA-\nrelated patient stratification. Comparison of healthy and malignant\ngene expression dynamics reveals dysregulation of the Wnt-\nantagonist SFRP1 at the quiescence to activation transition. SFRP1\noverexpression renders GBM quiescent and increases overall survival\nof tumor-bearing mice. Surprisingly, it does so through\nreprogramming the tumor’s stem-like methylome into an astrocyte-\nlike one. Our findings offer a framework for patient stratification with\nprognostic value, biomarker identification, and therapeutic avenues to\nhalt GBM progression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-22T07:29:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008156","title":"VIVO_Behjati_WellcomeCore_EMseq","description":"Whilst some genomic features of rhabdomyosarcoma are employed in diagnosis and risk stratification in current protocols, new genomic biomarker discovery has been frustrated by small study sample sizes, or necessary focus on a small number of genes/regions of interest. The VIVO biobank currently stores pathological samples from over 600 patients with RMS.  This study has coordinated high quality and detailed clinical annotation of these samples, facilitating the identification of a cohort of clinical outliers and matched controls. These will undergo extensive whole genomic and transcriptomic sequencing to identify novel risk biomarkers and further delineate the genomic landscape of RMS. ","abstract":"Whilst some genomic features of rhabdomyosarcoma are employed in diagnosis and risk stratification in current protocols, new genomic biomarker discovery has been frustrated by small study sample sizes, or necessary focus on a small number of genes/regions of interest. The VIVO biobank currently stores pathological samples from over 600 patients with RMS.  This study has coordinated high quality and detailed clinical annotation of these samples, facilitating the identification of a cohort of clinical outliers and matched controls. These will undergo extensive whole genomic and transcriptomic sequencing to identify novel risk biomarkers and further delineate the genomic landscape of RMS. ","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008157","title":"High-Resolution Spatial Transcriptomics Uncover Epidermal-Dermal Divergences in Merkel Cell Carcinoma: Spatial Context Reshapes the Gene Expression Landscape","description":"Merkel cell carcinoma (MCC) is an aggressive malignancy with neuroendocrine differentiation marked by high plasticity, often manifesting as rapid therapy resistance. Although the cell-of-origin is presumed to be epithelial, epidermal localization of MCC is rarely observed, largely because in situ MCC is typically an incidental finding. Nevertheless, a subset of MCC tumors exhibits epidermotropism, wherein tumor cells are present in the epidermis. The behavior of cancer cells is profoundly influenced by the tumor microenvironment and interactions with neighboring cells. Notably, the normal counterparts of the cancer’s cell-of-origin have been shown to attenuate tumor aggressiveness. Thus, epidermotropic MCC presents a unique opportunity to explore the potential role of surrounding keratinocytes in modulating tumor cell behavior. While the epidermotropic tumor nests share histological resemblance with their dermal counterparts, their transcriptomic profiles remain unexplored. Here, we employed high-definition spatial and single cell transcriptomics to dissect the gene expression profiles of epidermotropic MCC cells, comparing them to MCC cells in the tumor core and those adjacent to blood vessels. Notably, epidermotropic MCC cells exhibit a transcriptomic signature reminiscent of cutaneous squamous cell carcinoma, characterized by upregulation of genes encoding keratins, S100A proteins, as well as calmodulin-like proteins 3 and 5. Mechanistically, this keratinocytic differentiation is associated with enhanced p63 activity, leading to the upregulation of PERP. Collectively, our study demonstrates that MCC cells can adopt a keratinocytic differentiation program in response to microenvironmental cues, underscoring the remarkable phenotypic plasticity of this malignancy and the importance of the tumor microenvironment for tumor characteristics.","abstract":"Merkel cell carcinoma (MCC) is an aggressive malignancy with neuroendocrine differentiation marked by high plasticity, often manifesting as rapid therapy resistance. Although the cell-of-origin is presumed to be epithelial, epidermal localization of MCC is rarely observed, largely because in situ MCC is typically an incidental finding. Nevertheless, a subset of MCC tumors exhibits epidermotropism, wherein tumor cells are present in the epidermis. The behavior of cancer cells is profoundly influenced by the tumor microenvironment and interactions with neighboring cells. Notably, the normal counterparts of the cancer’s cell-of-origin have been shown to attenuate tumor aggressiveness. Thus, epidermotropic MCC presents a unique opportunity to explore the potential role of surrounding keratinocytes in modulating tumor cell behavior. While the epidermotropic tumor nests share histological resemblance with their dermal counterparts, their transcriptomic profiles remain unexplored. Here, we employed high-definition spatial and single cell transcriptomics to dissect the gene expression profiles of epidermotropic MCC cells, comparing them to MCC cells in the tumor core and those adjacent to blood vessels. Notably, epidermotropic MCC cells exhibit a transcriptomic signature reminiscent of cutaneous squamous cell carcinoma, characterized by upregulation of genes encoding keratins, S100A proteins, as well as calmodulin-like proteins 3 and 5. Mechanistically, this keratinocytic differentiation is associated with enhanced p63 activity, leading to the upregulation of PERP. Collectively, our study demonstrates that MCC cells can adopt a keratinocytic differentiation program in response to microenvironmental cues, underscoring the remarkable phenotypic plasticity of this malignancy and the importance of the tumor microenvironment for tumor characteristics.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-22T13:54:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008158","title":"CMML_WGS","description":"Whole genome sequencing to determine HSC phylogeny in MDS and clonal haematopoiesis patients undergoing treatment with hypomethylating agents","abstract":"Whole genome sequencing to determine HSC phylogeny in MDS and clonal haematopoiesis patients undergoing treatment with hypomethylating agents.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008159","title":"CMML_WGMS","description":"Whole genome methylation sequencing to determine HSC phylogeny in MDS and clonal haematopoiesis patients undergoing treatment with hypomethylating agents.","abstract":"Whole genome methylation sequencing to determine HSC phylogeny in MDS and clonal haematopoiesis patients undergoing treatment with hypomethylating agents.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008160","title":"Early_Cutaneous_T_Cell_Lymphoma__CTCL__","description":"This project aims to define, profile and investigate the landscape of CTCL disease progression and treatment resistance using a variety of single-cell and single-nuclei omics sequencing methods (e.g. multiome sequencing and proteomics), whole genome sequencing, and spatial transcriptomics and proteomics (e.g. Visium, Xenium and high-plex protein expression). ","abstract":"Cutaneous T cell lymphoma (CTCL) is a rare type of non-Hodgkin lymphoma that affects the skin and can present with varying prognoses. Despite recent advances in the understanding of the malignant T cells involved in CTCL, the tumour microenvironment (TME) and its impact on disease progression and therapy resistance remain largely unknown. This project aims to define, profile and investigate the landscape of CTCL disease progression and treatment resistance using a variety of single-cell and single-nuclei omics sequencing methods (e.g. multiome sequencing and proteomics), whole genome sequencing, and spatial transcriptomics and proteomics (e.g. Visium, Xenium and high-plex protein expression). ","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008161","title":"Single cell TCRseq data fromTIL and non-TIL expanded TRACERx samples in the manuscript Bulk TCRseq from TRACERx samples from 'Subclonal immune evasion in non-small cell lung cancer'  ","description":"Immune checkpoint blockade in non-small cell lung cancer (NSCLC) rarely leads to complete tumour remission, suggesting that tumours harbour subpopulations of cancer cells that can escape immune predation. However, while tumours consist of multiple genetically distinct clones, the extent to which separate tumour subclones differ intrinsically in their functional capacity for immune evasion remains largely unexplored. This has been challenging to address due to an inability to isolate and propagate individual tumour subclones from human cancers. Here, we leverage the multi-region TRACERx lung cancer evolution study to generate a patient-derived platform that allows the functional analysis of immune escape at single clone resolution. We generated libraries of &gt;20 separate NSCLC organoid lines per patient by isolating individual (clonal) organoids established from multiple spatially separated tumour regions. Each organoid subline was co-cultured with autologous tumour infiltrating lymphocytes (TIL) to evaluate their capacity to elicit a T cell response. Organoid lines derived from separate tumour regions, or from single clones within individual regions, differ vastly in their capacity to elicit a T cell response, showing the coexistence of intrinsically immune evading (‘cold) and non-evading (‘hot) clones in the same primary tumour. Organoid lines escaping T cell recognition represent genetically and transcriptionally unique subclones with a distinct evolutionary history, showing that evolutionary sculpting of subclonal diversity can have functional consequences for anti-tumour immunity. Notably, the identification of immune-evasive subclones would not have been possible using computational approaches alone, highlighting the unique value of functional co-culture platforms. This patient-derived functional co-culture platform reveals that tumour evolution can give rise to distinct cancer clones with intrinsic differences in immune evasion capacity and provides an approach to prospectively identify, isolate and characterise immune evading subclones from patients with cancer.","abstract":"Immune checkpoint blockade in non-small cell lung cancer (NSCLC) rarely leads to complete tumour remission, suggesting that tumours harbour subpopulations of cancer cells that can escape immune predation. However, while tumours consist of multiple genetically distinct clones, the extent to which separate tumour subclones differ intrinsically in their functional capacity for immune evasion remains largely unexplored. This has been challenging to address due to an inability to isolate and propagate individual tumour subclones from human cancers. Here, we leverage the multi-region TRACERx lung cancer evolution study to generate a patient-derived platform that allows the functional analysis of immune escape at single clone resolution. We generated libraries of &gt;20 separate NSCLC organoid lines per patient by isolating individual (clonal) organoids established from multiple spatially separated tumour regions. Each organoid subline was co-cultured with autologous tumour infiltrating lymphocytes (TIL) to evaluate their capacity to elicit a T cell response. Organoid lines derived from separate tumour regions, or from single clones within individual regions, differ vastly in their capacity to elicit a T cell response, showing the coexistence of intrinsically immune evading (‘cold) and non-evading (‘hot) clones in the same primary tumour. Organoid lines escaping T cell recognition represent genetically and transcriptionally unique subclones with a distinct evolutionary history, showing that evolutionary sculpting of subclonal diversity can have functional consequences for anti-tumour immunity. Notably, the identification of immune-evasive subclones would not have been possible using computational approaches alone, highlighting the unique value of functional co-culture platforms. This patient-derived functional co-culture platform reveals that tumour evolution can give rise to distinct cancer clones with intrinsic differences in immune evasion capacity and provides an approach to prospectively identify, isolate and characterise immune evading subclones from patients with cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-23T13:04:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008162","title":"Noorani_UGI_Early_Onset_LCMB","description":"Oesophageal cancer is the 6th most common cause of cancer death worldwide with an overall 5 year survival of 10-25%. State of the art sequencing technologies have demonstrated that canonical driver mutations occur in normal tissues across organ types, challenging traditional understanding of clonal evolution in cancer development and presenting the opportunity to detect hidden genomic alterations in tissues with an increased cancer risk. This study aims to comprehensively identify the genomic alterations in benign oesophageal diseases with an increased cancer risk, including Chagas mega-oesophagus in 200 cases. Through combined duplex sequencing and Laser Capture Microdissection we aim to reconstruct the landscape of these diseases in unprecedented detail.","abstract":"Comprehensive clonal analysis of early onset upper GI cancer &amp; normals - LCMB Samples","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008163","title":"Noorani_UGI_Early_Onset_re_nanoseq","description":"Oesophageal cancer is the 6th most common cause of cancer death worldwide with an overall 5 year survival of 10-25%. State of the art sequencing technologies have demonstrated that canonical driver mutations occur in normal tissues across organ types, challenging traditional understanding of clonal evolution in cancer development and presenting the opportunity to detect hidden genomic alterations in tissues with an increased cancer risk. This study aims to comprehensively identify the genomic alterations in benign oesophageal diseases with an increased cancer risk, including Chagas mega-oesophagus in 200 cases. Through combined duplex sequencing and Laser Capture Microdissection we aim to reconstruct the landscape of these diseases in unprecedented detail.","abstract":"Comprehensive clonal analysis of early onset upper GI cancer &amp; normals - re-nanoseq samples","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008164","title":"Noorani_UGI_Match_Normals","description":"Oesophageal cancer is the 6th most common cause of cancer death worldwide with an overall 5 year survival of 10-25%. State of the art sequencing technologies have demonstrated that canonical driver mutations occur in normal tissues across organ types, challenging traditional understanding of clonal evolution in cancer development and presenting the opportunity to detect hidden genomic alterations in tissues with an increased cancer risk. This study aims to comprehensively identify the genomic alterations in benign oesophageal diseases with an increased cancer risk, including Chagas mega-oesophagus in 200 cases. Through combined duplex sequencing and Laser Capture Microdissection we aim to reconstruct the landscape of these diseases in unprecedented detail.","abstract":"Match Normals used for germline comparison in comprehensive clonal analysis of oesopahgeal diseases with an increased cancer risk","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008165","title":"Noorani_UGI_Achalasia_LCMB","description":"Oesophageal cancer is the 6th most common cause of cancer death worldwide with an overall 5 year survival of 10-25%. State of the art sequencing technologies have demonstrated that canonical driver mutations occur in normal tissues across organ types, challenging traditional understanding of clonal evolution in cancer development and presenting the opportunity to detect hidden genomic alterations in tissues with an increased cancer risk. This study aims to comprehensively identify the genomic alterations in benign oesophageal diseases with an increased cancer risk, including Chagas mega-oesophagus in 200 cases. Through combined duplex sequencing and Laser Capture Microdissection we aim to reconstruct the landscape of these diseases in unprecedented detail.","abstract":"Achalasia Cohort LCMB Samples","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008166","title":"Noorani_UGI_Achalasia_re_nanoseq","description":"Oesophageal cancer is the 6th most common cause of cancer death worldwide with an overall 5 year survival of 10-25%. State of the art sequencing technologies have demonstrated that canonical driver mutations occur in normal tissues across organ types, challenging traditional understanding of clonal evolution in cancer development and presenting the opportunity to detect hidden genomic alterations in tissues with an increased cancer risk. This study aims to comprehensively identify the genomic alterations in benign oesophageal diseases with an increased cancer risk, including Chagas mega-oesophagus in 200 cases. Through combined duplex sequencing and Laser Capture Microdissection we aim to reconstruct the landscape of these diseases in unprecedented detail.","abstract":"Achalasia Cohort re-nanoseq Samples","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008167","title":"Noorani_UGI_Inherited_LCMB","description":"Oesophageal cancer is the 6th most common cause of cancer death worldwide with an overall 5 year survival of 10-25%. State of the art sequencing technologies have demonstrated that canonical driver mutations occur in normal tissues across organ types, challenging traditional understanding of clonal evolution in cancer development and presenting the opportunity to detect hidden genomic alterations in tissues with an increased cancer risk. This study aims to comprehensively identify the genomic alterations in benign oesophageal diseases with an increased cancer risk, including Chagas mega-oesophagus in 200 cases. Through combined duplex sequencing and Laser Capture Microdissection we aim to reconstruct the landscape of these diseases in unprecedented detail.","abstract":"Inherited Cancer Risk in UGI - LCMB Samples","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008168","title":"Protracted iNSC conversion","description":"Transcription factor-based direct conversion of somatic cells represents an interesting avenue for generating induced neural stem cells (iNSCs) from peripheral blood without transit through a pluripotent stage. While this paradigm has been shown to be associated with epigenetic de-aging, the dynamics of this process have remained unclear. Here, we used overexpression of the two reprogramming factors SOX2 and cMYC to generate iNSC from erythroid progenitors of donors ranging from neonatal to 101 years of age. Using an epigenetic clock algorithm, we corroborated our previous finding that iNSCs generated from aged donors show pronounced epigenetic de-aging, preserving around 13 % and 5 % of the original donor age at low and high passages, respectively. Studying the dynamic of epigenetic de-aging during iNSC conversion across time, we found that this process is largely protracted, continuing for several weeks and even beyond forced neuronal differentiation of iNSCs. Transcriptomic differences between young and old donor-derived iNSCs dissipate with extended time in conversion, too. Concordant with this observation, established iNSC lines lack age-associated cellular hallmarks, similar to induced pluripotent stem cells and their derivatives. Interestingly, time course analysis of DNA methylation and RNA sequencing data revealed that acquisition of a bona fide NSC signature extends greatly beyond the time point when proliferative PAX6-positive iNSCs emerge. The unexpected slow dynamics of these processes makes iNSC conversion an attractive model for dissecting the mechanisms underlying somatic transdifferentiation and de-aging.","abstract":"Transcription factor-based direct conversion of somatic cells represents an interesting avenue for generating induced neural stem cells (iNSCs) from peripheral blood without transit through a pluripotent stage. While this paradigm has been shown to be associated with epigenetic de-aging, the dynamics of this process have remained unclear. Here, we used overexpression of the two reprogramming factors SOX2 and cMYC to generate iNSC from erythroid progenitors of donors ranging from neonatal to 101 years of age. Using an epigenetic clock algorithm, we corroborated our previous finding that iNSCs generated from aged donors show pronounced epigenetic de-aging, preserving around 13 % and 5 % of the original donor age at low and high passages, respectively. Studying the dynamic of epigenetic de-aging during iNSC conversion across time, we found that this process is largely protracted, continuing for several weeks and even beyond forced neuronal differentiation of iNSCs. Transcriptomic differences between young and old donor-derived iNSCs dissipate with extended time in conversion, too. Concordant with this observation, established iNSC lines lack age-associated cellular hallmarks, similar to induced pluripotent stem cells and their derivatives. Interestingly, time course analysis of DNA methylation and RNA sequencing data revealed that acquisition of a bona fide NSC signature extends greatly beyond the time point when proliferative PAX6-positive iNSCs emerge. The unexpected slow dynamics of these processes makes iNSC conversion an attractive model for dissecting the mechanisms underlying somatic transdifferentiation and de-aging.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008169","title":"Pooled scRNA-seq of iPSC-derived neural stem cells from ADHD and control individuals","description":"This dataset comprises paired-end FASTQ files from single-cell RNA sequencing (scRNA-seq) of neural stem cells (NSCs) derived from induced pluripotent stem cells (iPSCs). The iPSCs were reprogrammed from somatic cells (keratinocytes, PBMCs, or lymphoblastoid cell lines) collected from individuals diagnosed with attention-deficit hyperactivity disorder (ADHD) and age-matched healthy controls (ages 6–18 years).\n\nReprogramming was carried out using the non-integrative Sendai virus system (CytoTune-iPS 2.0, Thermo Fisher Scientific), introducing OCT3/4, SOX2, KLF4, and cMYC. iPSCs were cultured in Essential 8 medium on vitronectin and underwent rigorous quality control including immunocytochemistry, qRT-PCR, mycoplasma testing, and SNP genotyping (Illumina Global Screening Array). NSCs were generated using a standardized neural induction protocol and validated via qRT-PCR and immunostaining for markers including PAX6, SOX2, NESTIN, TUJ1, and FOXG1.\n\nTwo independent scRNA-seq multiplexed experiments were performed: Experiment 1 (ADHD: n = 7; Control: n = 6) and Experiment 2 (ADHD: n = 9; Control: n = 7). Samples were pooled and demultiplexed using the Ensemblex algorithm, incorporating prior genotype data. After quality control filtering (&gt;500 unique RNA molecules per cell), 30,433 single-cell transcriptomes were retained. Differential gene expression analysis was conducted to identify transcriptional signatures associated with ADHD compared to controls.","abstract":"This dataset comprises paired-end FASTQ files from single-cell RNA sequencing (scRNA-seq) of neural stem cells (NSCs) derived from induced pluripotent stem cells (iPSCs). The iPSCs were reprogrammed from somatic cells (keratinocytes, PBMCs, or lymphoblastoid cell lines) collected from individuals diagnosed with attention-deficit hyperactivity disorder (ADHD) and age-matched healthy controls (ages 6–18 years).\n\nReprogramming was carried out using the non-integrative Sendai virus system (CytoTune-iPS 2.0, Thermo Fisher Scientific), introducing OCT3/4, SOX2, KLF4, and cMYC. iPSCs were cultured in Essential 8 medium on vitronectin and underwent rigorous quality control including immunocytochemistry, qRT-PCR, mycoplasma testing, and SNP genotyping (Illumina Global Screening Array). NSCs were generated using a standardized neural induction protocol and validated via qRT-PCR and immunostaining for markers including PAX6, SOX2, NESTIN, TUJ1, and FOXG1.\n\nTwo independent scRNA-seq multiplexed experiments were performed: Experiment 1 (ADHD: n = 7; Control: n = 6) and Experiment 2 (ADHD: n = 9; Control: n = 7). Samples were pooled and demultiplexed using the Ensemblex algorithm, incorporating prior genotype data. After quality control filtering (&gt;500 unique RNA molecules per cell), 30,433 single-cell transcriptomes were retained. Differential gene expression analysis was conducted to identify transcriptional signatures associated with ADHD compared to controls.","study_type":"Other","pubmed_ids":[33662736,33667761,36800023,37004448,39241453],"external_links":null,"is_released":true,"released_date":"2025-05-26T14:17:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008170","title":"PacBio Rare Disease Study","description":"This study leverages PacBio HiFi long-read sequencing technology to comprehensively analyze the genomic architecture of rare diseases. By generating highly accurate, long-read sequences, we aim to resolve complex structural variants, repeat expansions, and other genomic features that are often missed by short-read sequencing. Our approach facilitates improved variant detection and interpretation, advancing the understanding of rare disease etiology and enabling more precise genetic diagnoses.","abstract":"This study leverages PacBio HiFi long-read sequencing technology to comprehensively analyze the genomic architecture of rare diseases. By generating highly accurate, long-read sequences, we aim to resolve complex structural variants, repeat expansions, and other genomic features that are often missed by short-read sequencing. Our approach facilitates improved variant detection and interpretation, advancing the understanding of rare disease etiology and enabling more precise genetic diagnoses.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-26T14:53:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008171","title":"Genetics of male infertility in India","description":"The study comprises of whole exome and genome files of infertile males of Indian origin.","abstract":"The study comprises of whole exome and genome files of infertile males of Indian origin.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-27T08:29:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008172","title":"Early_Pregnancy_CUH_spatial","description":"Characterizing ectopic pregnancies using single cell and spatial methods\n","abstract":"Characterizing ectopic pregnancies using single cell and spatial methods\n","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008173","title":"B cell receptor silencing reveals origin and dependencies of high-grade B cell lymphomas with MYC and BCL2 rearrangements","description":"High-grade B cell lymphomas with MYC and BCL2 rearrangements (HGBCL-DH-BCL2) represent highly aggressive Germinal center (GC) derived B cell malignancies with dismal prognosis and limited therapeutic options. In the present study, we investigated the expression of BCR complex components, including immunoglobulin (IG) heavy (H) and light (L) chains, and CD79A and CD79B signaling subunits in HGBCL-DH-BCL2, scoring 65% of cases with undetectable IGH immunoreactivity (IGHUND). Transcriptomics (bulk RNA-seq) and genetic (whole exome/genome sequencing) analyses indicated that IGHUND and IGH+ HGBCL-DH-BCL2 lymphomas represent distinct biological entities. Specifically, IGHUND HGBCL-DH-BCL2 exhibit a GC DZ-like molecular program, and select subset-specific gene mutations pointing to distinct evolutionary trajectories respect to the IGH+ counterparts. IG profiling revealed that IGHUND HGBCL-DH-BCL2 preserved potentially productive, hypermutated IGH variable (V) gene rearrangements, indicating a selective advantage conferred to the malignant B cells by residual IGH molecules. Accordingly, disruption of the productively rearranged IGHG1 gene in BCRnull HGBCL-DH-BCL2 cell line model confirmed the dependency on IGH expression for optimal fitness. Using transcriptomics and in situ RNA-scope analysis, we reported that IGHUND HGBCL-DH-BCL2 originated from IG-class switched GC B cells, while IGH-expressing tumors were selected for continuous IGM expression. Moreover, while IGH+ HGBCL-DH-BCL2 favor IGM/IG-Kappa expression, IGHUND counterparts complete IG-Lambda light chain rearrangements. Notably, BCR silencing, caused by accelerated IGH turnover and reduced IGH expression, precedes HGBCL-DH-BCL2 onset, inducing RAG1/2-dependent IG light chain editing and eventually facilitating t(8;22)/IGL::MYC translocations. Finally, IGH silencing observed in HGBCL-DH-BCL2 cell models, which leads to intracellular retention/silencing of CD79B, results in reduced sensitivity to the CD79B-targeting antibody-drug conjugate Polatuzumab-vedotin. Collectively, HGBCL-DH-BCL2 originates from isotype-switched t(14;18)+ GC B cells that undergo IG light chain editing fuelling intra-clonal diversification, BCR silencing, and the acquisition of t(8;22) translocation, while preserving IGH dependency.","abstract":"High-grade B cell lymphomas with MYC and BCL2 rearrangements (HGBCL-DH-BCL2) represent highly aggressive Germinal center (GC) derived B cell malignancies with dismal prognosis and limited therapeutic options. In the present study, we investigated the expression of BCR complex components, including immunoglobulin (IG) heavy (H) and light (L) chains, and CD79A and CD79B signaling subunits in HGBCL-DH-BCL2, scoring 65% of cases with undetectable IGH immunoreactivity (IGHUND). Transcriptomics (bulk RNA-seq) and genetic (whole exome/genome sequencing) analyses indicated that IGHUND and IGH+ HGBCL-DH-BCL2 lymphomas represent distinct biological entities. Specifically, IGHUND HGBCL-DH-BCL2 exhibit a GC DZ-like molecular program, and select subset-specific gene mutations pointing to distinct evolutionary trajectories respect to the IGH+ counterparts. IG profiling revealed that IGHUND HGBCL-DH-BCL2 preserved potentially productive, hypermutated IGH variable (V) gene rearrangements, indicating a selective advantage conferred to the malignant B cells by residual IGH molecules. Accordingly, disruption of the productively rearranged IGHG1 gene in BCRnull HGBCL-DH-BCL2 cell line model confirmed the dependency on IGH expression for optimal fitness. Using transcriptomics and in situ RNA-scope analysis, we reported that IGHUND HGBCL-DH-BCL2 originated from IG-class switched GC B cells, while IGH-expressing tumors were selected for continuous IGM expression. Moreover, while IGH+ HGBCL-DH-BCL2 favor IGM/IG-Kappa expression, IGHUND counterparts complete IG-Lambda light chain rearrangements. Notably, BCR silencing, caused by accelerated IGH turnover and reduced IGH expression, precedes HGBCL-DH-BCL2 onset, inducing RAG1/2-dependent IG light chain editing and eventually facilitating t(8;22)/IGL::MYC translocations. Finally, IGH silencing observed in HGBCL-DH-BCL2 cell models, which leads to intracellular retention/silencing of CD79B, results in reduced sensitivity to the CD79B-targeting antibody-drug conjugate Polatuzumab-vedotin. Collectively, HGBCL-DH-BCL2 originates from isotype-switched t(14;18)+ GC B cells that undergo IG light chain editing fuelling intra-clonal diversification, BCR silencing, and the acquisition of t(8;22) translocation, while preserving IGH dependency.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008174","title":"Spatio-temporal Profiling of a Rhabdoid Tumor Case Study","description":"Background\nImmune checkpoint inhibition (ICI) has revolutionized oncology, offering extended survival and long-term remission in previously incurable cancers. While highly effective in tumors with high mutational burden, lowly mutated cancers, including pediatric malignancies, present low response rate and limited predictive biomarkers.\n\nPatients and methods\nWe present a framework for the identification and validation of tumor-reactive T cells as a biomarker to quantify ICI efficacy and as candidates for a personalized TCR-T cell therapy. Therefore, we profiled a pediatric malignant rhabdoid tumor patient with complete remission after ICI therapy using deep single-cell T cell receptor (TCR) repertoire sequencing of the tumor microenvironment (TME) and the peripheral blood.\n\nResults\nTracking T cell dynamics longitudinally from the tumor to cells in circulation over a time course of 12 months revealed a systemic response and durable clonal expansion of tumor-resident and ICI-induced TCR clonotypes. We functionally validated tumor reactivity of TCRs identified from the TME and the blood by co-culturing patient-derived tumor cells with TCR-engineered autologous T cells. Here, we observed unexpectedly high frequencies of tumor-reactive TCR clonotypes in the TME and confirmed T cell dynamics in the blood post-ICI to predict tumor-reactivity.\n\nConclusion\nThese findings strongly support spatio-temporal tracking of T cell activity in response to ICI to inform therapy efficacy and to serve as a source of tumor-reactive TCRs for personalized TCR-T designs.","abstract":"Background\nImmune checkpoint inhibition (ICI) has revolutionized oncology, offering extended survival and long-term remission in previously incurable cancers. While highly effective in tumors with high mutational burden, lowly mutated cancers, including pediatric malignancies, present low response rate and limited predictive biomarkers.\n\nPatients and methods\nWe present a framework for the identification and validation of tumor-reactive T cells as a biomarker to quantify ICI efficacy and as candidates for a personalized TCR-T cell therapy. Therefore, we profiled a pediatric malignant rhabdoid tumor patient with complete remission after ICI therapy using deep single-cell T cell receptor (TCR) repertoire sequencing of the tumor microenvironment (TME) and the peripheral blood.\n\nResults\nTracking T cell dynamics longitudinally from the tumor to cells in circulation over a time course of 12 months revealed a systemic response and durable clonal expansion of tumor-resident and ICI-induced TCR clonotypes. We functionally validated tumor reactivity of TCRs identified from the TME and the blood by co-culturing patient-derived tumor cells with TCR-engineered autologous T cells. Here, we observed unexpectedly high frequencies of tumor-reactive TCR clonotypes in the TME and confirmed T cell dynamics in the blood post-ICI to predict tumor-reactivity.\n\nConclusion\nThese findings strongly support spatio-temporal tracking of T cell activity in response to ICI to inform therapy efficacy and to serve as a source of tumor-reactive TCRs for personalized TCR-T designs.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-28T08:23:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008175","title":"Methylation data for Genomic landscapes of endometrioid and mucinous ovarian cancers and morphologically similar tumor types","description":null,"abstract":"While endometrioid and mucinous ovarian carcinomas represent nearly a fifth of ovarian cancers, their molecular characteristics and pathologic origins are poorly understood. To identify the genomic and epigenomic alterations characteristic of these ovarian cancer subtypes and to evaluate links to morphologically similar tumors from other sites, we performed a combination of sequence, copy number, mutation signature, and rearrangement analyses from tumor samples and matched normal tissues of 133 patients, as well as methylation analyses of these tumors and tissues of 150 patients from the Cancer Genome Atlas. Genomic analyses included samples from patients with ovarian endometrioid (n=44), ovarian mucinous (n=43), uterine endometrioid (n=15), and gastrointestinal mucinous carcinomas (n=31), including mucinous carcinomas of the stomach, colon, and pancreas. In addition to identifying genes previously known to be involved in these tumors, we identified alterations in RAD51C, NOTCH4, SMARCA1/4 and JAK1 in ovarian endometrioid, ESR1 in uterine endometrioid, and SMARCA4 in ovarian mucinous carcinomas. Whole genome sequencing revealed rearrangements involving PTEN, NF1, and NF2 in ovarian endometrioid carcinomas, and NF1 and MED1 in ovarian mucinous carcinomas. The number of alterations and affected genes as well as genome-wide methylation profiles were not distinguishable between ovarian and uterine endometrioid carcinomas, supporting the hypothesis that these tumors share a tissue of origin. In contrast, mutation and methylation patterns in ovarian mucinous carcinomas were different from gastrointestinal mucinous carcinomas. These analyses provide insights into the genomic landscapes and origins of mucinous and endometrioid ovarian carcinomas, providing new avenues for early clinical intervention and management of patients with these cancers. ","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-29T17:10:30+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008176","title":"Whole-genome sequencing and transcriptome sequencing of sarcoma patient tumors used for 3D model generation in the MASTER precision oncology registry","description":"Sarcomas are rare and biologically heterogeneous mesenchymal malignancies with limited availability of representative patient-derived models. We established a collection of individualized three-dimensional (3D) sarcoma cultures, i.e. organoids and spheroids, from patients enrolled in the MASTER trial, a precision oncology registry led by the German Cancer Research Center (DKFZ), the National Center for Tumor Diseases (NCT) Heidelberg and Dresden and the German Cancer Consortium (DKTK). This repository provides whole-genome sequencing (WGS) and bulk RNA sequencing data from the original patient tumors used for model generation. The dataset enables molecular comparison of primary patient tissue with sequencing data from derived cultures and offers a resource for studying sarcoma biology, subtype-specific features, and microenvironmental dependencies.","abstract":"Sarcomas are rare and biologically heterogeneous mesenchymal malignancies with limited availability of representative patient-derived models. We established a collection of individualized three-dimensional (3D) sarcoma cultures, i.e. organoids and spheroids, from patients enrolled in the MASTER trial, a precision oncology registry led by the German Cancer Research Center (DKFZ), the National Center for Tumor Diseases (NCT) Heidelberg and Dresden and the German Cancer Consortium (DKTK). This repository provides whole-genome sequencing (WGS) and bulk RNA sequencing data from the original patient tumors used for model generation. The dataset enables molecular comparison of primary patient tissue with sequencing data from derived cultures and offers a resource for studying sarcoma biology, subtype-specific features, and microenvironmental dependencies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008177","title":"Transcriptomic predictors of survival for palbociclib + endocrine therapy vs. capecitabine in aromatase inhibitor-resistant breast cancer from GEICAM/2013-02 PEARL","description":"We examined transcriptomic tumor features associated with survival from GEICAM/2013-02 PEARL, a phase III trial of palbociclib + ET vs. capecitabine in aromatase inhibitor-resistant HR+/HER2- MBC. PAM50 intrinsic subtype predicted PFS differences between palbociclib + ET and capecitabine, and lower B-cell-associated gene expression predicted longer OS with palbociclib + ET vs. capecitabine. These features may help identify HR+/HER2- tumors resistant to further ET-based treatment with CDK4/6 inhibitors.","abstract":"We examined transcriptomic tumor features associated with survival from GEICAM/2013-02 PEARL, a phase III trial of palbociclib + ET vs. capecitabine in aromatase inhibitor-resistant HR+/HER2- MBC. PAM50 intrinsic subtype predicted PFS differences between palbociclib + ET and capecitabine, and lower B-cell-associated gene expression predicted longer OS with palbociclib + ET vs. capecitabine. These features may help identify HR+/HER2- tumors resistant to further ET-based treatment with CDK4/6 inhibitors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-05-30T16:58:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008178","title":"Spatially_resolved_host_pathogen_interactions_across_the_cystic_fibrosis_lung","description":"Our aim is to adapt existing spatial transcriptomic methods to capture both host and bacterial transcripts in parallel in order to identify host-pathogen interactions across the lungs of cystic fibrosis patients.\n\nAIMS\n1.\tSpatial diversity in pathogen virulence gene expression and subclonal composition across the lung\n\n\n2.\tSpatial transcriptomics approach using bacterial virulence panel from FFPE tissue blocks collected from CF explanted lungs \n\n\n3.\tOverlay host spatial transcriptomics of lung tissues from cystic fibrosis to uncover host-pathogen interactions\n\nThis study is for the RNAseq portion of the project.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Bacterial infections of CF patients with Mycobacterium abscessus and Pseudomonas aeruginosa are very difficult to treat, and therefore almost all adults with CF are chronically colonised with at least one of these pathogens. The duration of these infections allows the evolution of subclonal diversity and adaptation to the lung environment over time.\nHowever, in addition to temporal diversity it is thought there may be significant spatial diversity in microbial populations across the lung. The anatomy lung is highly compartmentalized and heterogenous in terms of macrostructures in addition to the distribution of cell types, creating diverse microenvironmental niches for bacteria to exploit. In this study we are exploring the spatial genomic and transcriptomic diversity of CF pathogens  and the resident host cells across lung tissue to better understand host-pathogen interactions.     \n","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008179","title":"High_plex_and_high_resolution_spatial_profiling_of_human_thymi_during_development__and_ageing_","description":"High-plex and high-resolution spatial profiling of human thymi during development, and ageing.","abstract":"\"The thymus is a primary lymphoid organ that provides an essential environment for T lymphocyte precursors to differentiate into naive T cells. In our previous work we used single-cell RNA sequencing to study T cell development directly in the human thymus, providing new insights into the diversity and dynamics of thymic cell types during development (Park 2020, Science). More recently, we have applied spatial transcriptomics at 50 μm resolution with high-resolution low-plex approaches to profile thymic architecture and infer the location of thymic cell types in foetal and paediatric samples (Yayon, Kedlian, Boehme 2024, Nature). \nIn this study, we will use high-plexity and high-resolution spatial transcriptomics, complemented with paired single-cell transcriptomics data from adjacent sections, and multiplexed immunostaining assays to profile human thymi during foetal and paediatric development, and ageing. This will allow us to capture temporal changes in the molecular profiles and spatial organisation of developing T cells and various resident stromal and immune cell populations. This approach aims to reveal how thymus morphology, cellular composition, spatial niches and cell function change across the lifespan.\n\"","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008180","title":"Single_cell_profiling_of_human_thymi_during_development_and_ageing","description":"Single cell profiling of human thymi during development and ageing","abstract":"The thymus is a primary lymphoid organ that provides an essential environment for T lymphocyte precursors to differentiate into naive T cells. In our previous work we used single-cell RNA sequencing to study T cell development directly in the human thymus, providing new insights into the diversity and dynamics of thymic cell types during development (Park 2020, Science). More recently, we have applied spatial transcriptomics at 50 μm resolution with high-resolution low-plex approaches to profile thymic architecture and infer the location of thymic cell types in foetal and paediatric samples (Yayon, Kedlian, Boehme 2024, Nature). \nIn this study, we will use high-plexity and high-resolution spatial transcriptomics, complemented with paired single-cell transcriptomics data from adjacent sections, and multiplexed immunostaining assays to profile human thymi during foetal and paediatric development, and ageing. This will allow us to capture temporal changes in the molecular profiles and spatial organisation of developing T cells and various resident stromal and immune cell populations. This approach aims to reveal how thymus morphology, cellular composition, spatial niches and cell function change across the lifespan.\n","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008181","title":"scRNA-seq to study interactions between HSPCs, BMSCs and immune microenvironment","description":"Mechanisms of clonal evolution in myeloid neoplasms remain incompletely understood. Darwinian theory predicts that the (micro)environment of clone-propagating stem cells may contribute to clonal selection. Here, we provide data fitting this model, establishing a relationship between stromal niche inflammation, inflammatory stress in HSPCs, clonal resistance and leukemic evolution in human MDS.","abstract":"Mechanisms of clonal evolution in myeloid neoplasms remain incompletely understood. Darwinian theory predicts that the (micro)environment of clone-propagating stem cells may contribute to clonal selection. Here, we provide data fitting this model, establishing a relationship between stromal niche inflammation, inflammatory stress in HSPCs, clonal resistance and leukemic evolution in human MDS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-06-03T12:40:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008182","title":"RNA-seq of CD34+ HSPCs from LRMDS patients","description":"To profile transcriptional alterations of HSPCs in LR-MDS patients, 7AAD−CD45+Lin-CD235a−CD34+ cells were isolated from healthy donors and LR-MDS patients for RNA sequencing. ","abstract":"To profile transcriptional alterations of HSPCs in LR-MDS patients, 7AAD−CD45+Lin-CD235a−CD34+ cells were isolated from healthy donors and LR-MDS patients for RNA sequencing. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-06-03T12:49:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008183","title":"DERMATLAS__Cribriform_carcinoma_breast_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are cribriform carcinoma of the breast, to compare to their cutaneous counterpart.","abstract":" Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are apocrine carcinoma of the breast, to compare to their cribriform counterpart.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008184","title":"DERMATLAS__Cribriform_carcinoma_breast_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n        The cases in this cohort are apocrine carcinoma of the breast, to compare to their cribriform counterpart.","abstract":" Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are apocrine carcinoma of the breast, to compare to their cribriform counterpart.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008185","title":"Short and Long read RNA sequence data for HKCI-10. Data of all the samples were stored in compressed format.","description":"RNA sequence data for HKCI-10. The HKCI-10 sample is inhouse cell line derived from HCC samples. There are 2 matched short and long read RNA sequencing samples.  Data of all the samples were stored in compressed format.","abstract":"RNA sequence data for HKCI-10. Data of all the samples were stored in compressed format.","study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008186","title":"KAT6A and KAT7 Histone Acetyltransferase Complexes Are Molecular Dependencies and Therapeutic Targets in NUP98-Rearranged Acute Myeloid Leukemia","description":"NUP98 fusion oncoproteins (FOs) are a hallmark of childhood acute myeloid leukemia (AML). NUP98 FOs drive leukemogenesis through phase-separated condensate formation and maintenance of an active chromatin landscape at stem cell-associated genes in cooperation with epigenetic regulators. Here we show that MYST family histone acetyltransferase (HAT) complex proteins including KAT6A/MOZ, KAT7/HBO1, and the common KAT6A/7 complex subunit BRPF1 associate with NUP98 FOs on chromatin and within condensates.  MYST HATs are molecular dependencies in NUP98-rearranged (NUP98-r) leukemia, and genetic inactivation or pharmacologic inhibition of Kat6a and Kat7 impairs NUP98-r cell fitness. KAT6A/7 inhibition decreased global H3K23ac levels, displaced NUP98::HOXA9 from chromatin at the Meis1 locus, and led to myeloid cell differentiation. Additionally, KAT6A/7 inhibition decreased leukemic burden in multiple NUP98-r leukemia xenograft mouse models, synergized with Menin inhibitor treatment, and was efficacious in Menin inhibitor-resistant cells. In summary, we show that MYST family HATs are therapeutically actionable dependencies in NUP98-r AML.","abstract":"NUP98 fusion oncoproteins (FOs) are a hallmark of childhood acute myeloid leukemia (AML). NUP98 FOs drive leukemogenesis through phase-separated condensate formation and maintenance of an active chromatin landscape at stem cell-associated genes in cooperation with epigenetic regulators. Here we show that MYST family histone acetyltransferase (HAT) complex proteins including KAT6A/MOZ, KAT7/HBO1, and the common KAT6A/7 complex subunit BRPF1 associate with NUP98 FOs on chromatin and within condensates.  MYST HATs are molecular dependencies in NUP98-rearranged (NUP98-r) leukemia, and genetic inactivation or pharmacologic inhibition of Kat6a and Kat7 impairs NUP98-r cell fitness. KAT6A/7 inhibition decreased global H3K23ac levels, displaced NUP98::HOXA9 from chromatin at the Meis1 locus, and led to myeloid cell differentiation. Additionally, KAT6A/7 inhibition decreased leukemic burden in multiple NUP98-r leukemia xenograft mouse models, synergized with Menin inhibitor treatment, and was efficacious in Menin inhibitor-resistant cells. In summary, we show that MYST family HATs are therapeutically actionable dependencies in NUP98-r AML.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008187","title":"Multi-modal analysis of pediatric pilocytic astrocytomas reveals tumor location-associated cellular and transcriptional heterogeneity","description":null,"abstract":"Background: Pilocytic astrocytomas (PAs) are the most common pediatric central nervous system (CNS) tumors, which present with limited genetic but significant clinical heterogeneity. Current treatment strategies are partly effective, but tumors often progress, and patients experience long-term side effects, highlighting the need for additional novel therapeutic approaches. A promising alternative approach could be targeting the tumor immune microenvironment (TIME), however, a comprehensive overview of the TIME of PAs across different anatomical tumor locations is currently lacking. Methods: We employed a multi-modal, integrative approach using single-nucleus and bulk RNA-sequencing alongside high-dimensional immunofluorescence imaging and flow cytometry to elucidate the transcriptional landscape and cellular composition of pediatric PAs across tumor locations. Results: Our analysis uncovered neoplastic cell transcriptional heterogeneity reflective of  aberrant glial differentiation. Moreover, we provided a detailed characterization of the TIME, revealing pro-inflammatory brain-resident microglia and abundant activated monocyte-derived macrophages and T cells. Deconvolution of bulk RNA-sequencing data revealed variation in tumor and TIME composition across anatomical tumor locations.  Suprasellar tumors additionally exhibited increased expression of immune-related genes compared to tumors arising in other anatomical locations. Conclusions: Together, our multi-modal in-depth characterization provides detailed insights into the transcriptional and cellular heterogeneity of pediatric PAs across distinct anatomical tumor locations, which could aid in the development of novel (immuno)therapeutic approaches.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-06-06T10:53:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008188","title":"Brain_Disease_Wellcome_Leap_Delta_Tissue__Phase_2_RNA","description":"Utilising Single-Nucleus sequencing to investigate how the tumour microenvironment regulates glioblastoma cell states.","abstract":"Utilising Single-Nucleus sequencing and spatial technologies to investigate how the tumour microenvironment regulates glioblastoma cell states. (Phase 2 data, refer to study 6716 for Phase 1 transcriptome data).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008189","title":"Identifying genetic variants that alter TCR usage in the peripheral repertoire","description":"The relationship between genetic variation and CD8+ T-cell receptor (TCR) repertoire usage in patients receiving Immune Checkpoint Blockade (ICB) therapy for cancer is unexplored. We have conducted a genome-wide and human leukocyte antigen (HLA)-focused analysis of CD8+ T-cell TCR repertoire to identify genetic determinants of variable gene (V-gene) and CDR3 K-mer usage from samples taken prior to and after ICB (n=250). We identify 11 cis and 10 trans V-gene associations, primarily to the MHC, that meet genome-wide significance. TCR clones containing HLA associated V-genes were less stable across treatment, whilst at the single-cell level, genetically associated clones demonstrate subset enrichment and increased tumor reactivity expression profiles. Notably, patients with HLA-matched TCR clones demonstrate improved overall survival. Our work indicates a complex relationship between genotype and TCR repertoire in the context of ICB treatment, with novel implications for understanding factors relating to therapeutic response and patient outcomes.","abstract":"The relationship between genetic variation and CD8+ T-cell receptor (TCR) repertoire usage in patients receiving Immune Checkpoint Blockade (ICB) therapy for cancer is unexplored. We have conducted a genome-wide and human leukocyte antigen (HLA)-focused analysis of CD8+ T-cell TCR repertoire to identify genetic determinants of variable gene (V-gene) and CDR3 K-mer usage from samples taken prior to and after ICB (n=250). We identify 11 cis and 10 trans V-gene associations, primarily to the MHC, that meet genome-wide significance. TCR clones containing HLA associated V-genes were less stable across treatment, whilst at the single-cell level, genetically associated clones demonstrate subset enrichment and increased tumor reactivity expression profiles. Notably, patients with HLA-matched TCR clones demonstrate improved overall survival. Our work indicates a complex relationship between genotype and TCR repertoire in the context of ICB treatment, with novel implications for understanding factors relating to therapeutic response and patient outcomes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008190","title":"Fragmentomics Uncover Non-Mutational HRD Features","description":"Homologous recombination deficiency (HRD) is a key biomarker in prostate cancer (PCa), predicting response to PARP inhibitors and platinum-based therapies. However, current diagnostics often rely solely on BRCA1/2 mutations or genomic scars, missing cases driven by other mechanisms. Tissue-based testing is further limited by tumor heterogeneity and biopsy challenges in metastatic bone disease. Here, we applied a comprehensive multimodal approach to assess HRD in 106 advanced PCa patients using circulating tumor DNA (ctDNA). This included targeted sequencing of homologous recombination repair (HRR) genes, low-pass WGS for genomic instability (sHRD), WES for mutational signatures, and cfDNA fragmentomics and chromatin accessibility profiling. BRCA2 was the most frequently altered gene, often co-occurring with PTEN loss. High sHRD scores correlated with BRCA2/RB1 loss, somatic copy number alterations, and poor survival. HRD tumors showed enrichment of SBS3/ID6 signatures, altered fragment lengths, and reduced accessibility at zinc finger transcription factor sites. These results support ctDNA-based multimodal profiling as a non-invasive strategy for HRD detection and stratification.","abstract":"Homologous recombination deficiency (HRD) is a key biomarker in prostate cancer (PCa), predicting response to PARP inhibitors and platinum-based therapies. However, current diagnostics often rely solely on BRCA1/2 mutations or genomic scars, missing cases driven by other mechanisms. Tissue-based testing is further limited by tumor heterogeneity and biopsy challenges in metastatic bone disease. Here, we applied a comprehensive multimodal approach to assess HRD in 106 advanced PCa patients using circulating tumor DNA (ctDNA). This included targeted sequencing of homologous recombination repair (HRR) genes, low-pass WGS for genomic instability (sHRD), WES for mutational signatures, and cfDNA fragmentomics and chromatin accessibility profiling. BRCA2 was the most frequently altered gene, often co-occurring with PTEN loss. High sHRD scores correlated with BRCA2/RB1 loss, somatic copy number alterations, and poor survival. HRD tumors showed enrichment of SBS3/ID6 signatures, altered fragment lengths, and reduced accessibility at zinc finger transcription factor sites. These results support ctDNA-based multimodal profiling as a non-invasive strategy for HRD detection and stratification.","study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008191","title":"Epithelial Subpopulations Prognostic of Treatment Outcomes in Nasopharyngeal Cancer","description":"Intratumoral and intertumoral heterogeneity in nasopharyngeal carcinoma (NPC) has been inadequately studied, particularly regarding clonal evolution and relapse. \n\nWe conducted a paired multi-tissue single-cell RNA sequencing (scRNA-seq) study involving 74 untreated non-metastatic NPC patients at initial diagnosis. We analyzed copy number and single nucleotide variations to identify neoplastic subpopulations and their clonal evolutionary history. Clustering and survival analyses were conducted to correlate epithelial subpopulations with relapse-free survival (RFS). \n\nA total of 84,187 epithelial cells were profiled. Over a median follow-up of 40.7 months, 5 (7%) patients relapsed early. Nine major epithelial subpopulations were identified. Notably the LY6D-positive neoplastic secretory-primed basal cells (SPB), particularly SPB1, which were enriched with chemoresistant and radioresistant genes, were found to correlate strongly with early relapse. Multivariable Cox regression indicated that neoplastic SPB1 presence and LY6D expression were independent prognostic factors for RFS. V49G mutation of ATPAF1 in neoplastic SPB1 was linked to early relapse and a unique evolutionary trajectory.\n\nTo conclude, LY6D-positive neoplastic cells, especially the SPB1 subpopulation and its ATPAF1 mutant, enriched with chemoresistant and radioresistant genes, are associated with an increased risk of early relapse in NPC.","abstract":"Intratumoral and intertumoral heterogeneity in nasopharyngeal carcinoma (NPC) has been inadequately studied, particularly regarding clonal evolution and relapse. \n\nWe conducted a paired multi-tissue single-cell RNA sequencing (scRNA-seq) study involving 74 untreated non-metastatic NPC patients at initial diagnosis. We analyzed copy number and single nucleotide variations to identify neoplastic subpopulations and their clonal evolutionary history. Clustering and survival analyses were conducted to correlate epithelial subpopulations with relapse-free survival (RFS). \n\nA total of 84,187 epithelial cells were profiled. Over a median follow-up of 40.7 months, 5 (7%) patients relapsed early. Nine major epithelial subpopulations were identified. Notably the LY6D-positive neoplastic secretory-primed basal cells (SPB), particularly SPB1, which were enriched with chemoresistant and radioresistant genes, were found to correlate strongly with early relapse. Multivariable Cox regression indicated that neoplastic SPB1 presence and LY6D expression were independent prognostic factors for RFS. V49G mutation of ATPAF1 in neoplastic SPB1 was linked to early relapse and a unique evolutionary trajectory.\n\nTo conclude, LY6D-positive neoplastic cells, especially the SPB1 subpopulation and its ATPAF1 mutant, enriched with chemoresistant and radioresistant genes, are associated with an increased risk of early relapse in NPC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008192","title":"Targeted_NanoSeq__salivary_gland_","description":"Exploring the somatic mutation landscape of salivary gland disorders.","abstract":"Exploring the somatic mutation landscape of salivary gland disorders.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008193","title":"DERMATLAS__SCC_and_BCC_EMseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are SCC and BCC for a methylation study.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are SCC and BCC for a methylation study.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008194","title":"LCMB_WGS_human_HSPC","description":"The objective of this project is to define the impact of ageing on haematopoietic stem cells by performing molecular and functional single cell analysis of HSPC from young and aged human donors. \nHuman hematopoietic stem cells and progenitors (CD34+ cells) will be isolated from the bone marrow of young (&lt;35 years) and aged (&gt;60 years) adults without haematological disorders. CD34+ cells for each donor will undergo several experimental procedures. We will generate colonies from single cells and genotype them to build a phylogenetic tree and assess clonality. DNA extracted from colonies will undergo whole genome sequencing, with the goal of generating a phylogenetic tree.\n","abstract":"The objective of this project is to define the impact of ageing on haematopoietic stem cells by performing molecular and functional single cell analysis of HSPC from young and aged human donors. \nHuman hematopoietic stem cells and progenitors (CD34+ cells) will be isolated from the bone marrow of young (&lt;35 years) and aged (&gt;60 years) adults without haematological disorders. CD34+ cells for each donor will undergo several experimental procedures. We will generate colonies from single cells and genotype them to build a phylogenetic tree and assess clonality. DNA extracted from colonies will undergo whole genome sequencing, with the goal of generating a phylogenetic tree.\n","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008195","title":"Multimodal plasma and urinary cell-free DNA profiling improves risk stratification in newly diagnosed prostate cancer","description":"Prostate cancer (PCa) is a heterogeneous disease, impeding early detection and risk stratification. Liquid biopsies (LBx) enable minimally invasive tumor profiling, but circulating tumor-derived DNA (ctDNA) detection remains difficult, particularly in early-stage PCa. We developed a multimodal LBx approach combining genomic and epigenomic cell-free DNA (cfDNA) features in plasma and urine from newly diagnosed PCa patients to improve early characterization of PCa and risk stratification of aggressive disease. Plasma and urine samples from 55 localized PCa (lPCa) patients, 18 advanced PCa (aPCa) patients, and 36 cancer-free controls were subjected to low-coverage whole-genome sequencing and methylated DNA immunoprecipitation sequencing to assess fragmentation, chromosomal instability, and methylation in cfDNA. This complementary approach yielded a 45% ctDNA detection rate in newly diagnosed PCa. Major differences were observed between aPCa and controls, reflecting increasing signals with tumor progression. Epigenomic cfDNA features differentiated lPCa from aPCa, and ctDNA was detected in 46% of PCa patients with prostate-specific antigen &lt;10 ng/ml, suggesting potential for risk stratification. This study highlights the value of multimodal LBx approaches for early characterization of primary PCa and identification of aggressive disease at initial diagnosis. Integration into clinical workflows could complement diagnostics and support personalized decision-making tailored to patients’ PCa risk profiles. ","abstract":"Prostate cancer (PCa) is a heterogeneous disease, impeding early detection and risk stratification. Liquid biopsies (LBx) enable minimally invasive tumor profiling, but circulating tumor-derived DNA (ctDNA) detection remains difficult, particularly in early-stage PCa. We developed a multimodal LBx approach combining genomic and epigenomic cell-free DNA (cfDNA) features in plasma and urine from newly diagnosed PCa patients to improve early characterization of PCa and risk stratification of aggressive disease. Plasma and urine samples from 55 localized PCa (lPCa) patients, 18 advanced PCa (aPCa) patients, and 36 cancer-free controls were subjected to low-coverage whole-genome sequencing and methylated DNA immunoprecipitation sequencing to assess fragmentation, chromosomal instability, and methylation in cfDNA. This complementary approach yielded a 45% ctDNA detection rate in newly diagnosed PCa. Major differences were observed between aPCa and controls, reflecting increasing signals with tumor progression. Epigenomic cfDNA features differentiated lPCa from aPCa, and ctDNA was detected in 46% of PCa patients with prostate-specific antigen &lt;10 ng/ml, suggesting potential for risk stratification. This study highlights the value of multimodal LBx approaches for early characterization of primary PCa and identification of aggressive disease at initial diagnosis. Integration into clinical workflows could complement diagnostics and support personalized decision-making tailored to patients’ PCa risk profiles. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-06-11T13:39:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008196","title":"EPICYCLE: a confirmatory preclinical study of the anti-rhabdomyosarcoma efficacy of BET bromodomain and cyclin-dependent kinase 9 inhibitors","description":"Introduction: Hypothesis-driven academic research identifies candidate interventions with likely disease-specific effects. Yet, many candidate drugs fail upon further development, emphasizing the need for acquisition of more robust preclinical data. The overarching goal of this study was to assess the feasibility of planning and executing a confirmatory preclinical trial in an academic research setting. \nExperimental procedures: As BET bromodomain protein 4 (BRD4) and cyclin-dependent kinase 9 (CDK9) inhibitors may represent promising candidates for the treatment of PAX3::FOXO1 (P3F)-positive rhabdomyosarcoma (RMS), an investigator-initiated confirmatory preclinical study was established to validate their synergistic effects. Multicenter, randomized, blinded experiments were guided by a preclinical study protocol, which specified study endpoints, sample sizes, statistical approach, and quality measures. Study endpoints were cell proliferation, organoid growth, and apoptosis of 7 low-passage, P3F+ patient derived xenograft (PDX)-derived RMS cell cultures, penetrance of P3F+ mouse RMS xenografts, and growth of 9 P3F+ PDX tumors in mice.  \nResults: The primary objective of the study – to confirm synergistic anti-RMS effects of BRD4 and CDK9 inhibition – was not met. Post-hoc analyses support that single-agent JQ1 and the combination effectively reduced the growth and viability of P3F+ RMS cells ex vivo with adequate on-target activity as evidenced by reduced expression of P3F, MYCN, MYOG, and MYOD. Yet, in vivo growth assays were flawed by lower xenograft penetrance, variable xenograft latency, substantial gastrointestinal toxicity, and a lack of on-target activity for drugs administered in vivo. Gender stratification of in vivo assays and quality control measures were carried out successfully.  \nConclusions: Confirmatory preclinical trials allow for robust assessment of the efficacy of candidate interventions and reduce bias in academic research. The study platform established here provides a framework that may be adapted to other confirmatory preclinical efforts. \n","abstract":"Introduction: Hypothesis-driven academic research identifies candidate interventions with likely disease-specific effects. Yet, many candidate drugs fail upon further development, emphasizing the need for acquisition of more robust preclinical data. The overarching goal of this study was to assess the feasibility of planning and executing a confirmatory preclinical trial in an academic research setting. \nExperimental procedures: As BET bromodomain protein 4 (BRD4) and cyclin-dependent kinase 9 (CDK9) inhibitors may represent promising candidates for the treatment of PAX3::FOXO1 (P3F)-positive rhabdomyosarcoma (RMS), an investigator-initiated confirmatory preclinical study was established to validate their synergistic effects. Multicenter, randomized, blinded experiments were guided by a preclinical study protocol, which specified study endpoints, sample sizes, statistical approach, and quality measures. Study endpoints were cell proliferation, organoid growth, and apoptosis of 7 low-passage, P3F+ patient derived xenograft (PDX)-derived RMS cell cultures, penetrance of P3F+ mouse RMS xenografts, and growth of 9 P3F+ PDX tumors in mice.  \nResults: The primary objective of the study – to confirm synergistic anti-RMS effects of BRD4 and CDK9 inhibition – was not met. Post-hoc analyses support that single-agent JQ1 and the combination effectively reduced the growth and viability of P3F+ RMS cells ex vivo with adequate on-target activity as evidenced by reduced expression of P3F, MYCN, MYOG, and MYOD. Yet, in vivo growth assays were flawed by lower xenograft penetrance, variable xenograft latency, substantial gastrointestinal toxicity, and a lack of on-target activity for drugs administered in vivo. Gender stratification of in vivo assays and quality control measures were carried out successfully.  \nConclusions: Confirmatory preclinical trials allow for robust assessment of the efficacy of candidate interventions and reduce bias in academic research. The study platform established here provides a framework that may be adapted to other confirmatory preclinical efforts. \n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008197","title":"The genomic landscape of relapsed infant and childhood KMT2A-rearranged acute leukemia","description":"To study the mechanisms of relapse in KMT2A-rearranged (KMT2A-r) acute lymphoblastic (ALL) and acute myeloid leukemia (AML), we performed whole-genome and exome sequencing of infants and children with relapsed ALL/AML (n=36), and longitudinal deep-sequencing of 257 samples in 30 patients. Somatic alterations in drug-response genes, most commonly in TP53 and IKZF1 (64%), were highly enriched in early relapse ALL (79%, 9-36 months after diagnosis), but rare in very early relapse ALL (&lt;9 months, 9%). A marked chemotherapy-exposure signature was detected for mutations in early relapse ALL but not in very early ALL or AML relapse, in line with different mechanisms of relapse. Longitudinal analyses could track residual leukemia cells, clonal drug responses, and the upcoming relapse. These results highlight that KMT2A-r ALL and AML evade therapy differently and provide new insights into the mechanisms of relapse in this highly lethal form of pediatric acute leukemia.","abstract":"To study the mechanisms of relapse in KMT2A-rearranged (KMT2A-r) acute lymphoblastic (ALL) and acute myeloid leukemia (AML), we performed whole-genome and exome sequencing of infants and children with relapsed ALL/AML (n=36), and longitudinal deep-sequencing of 257 samples in 30 patients. Somatic alterations in drug-response genes, most commonly in TP53 and IKZF1 (64%), were highly enriched in early relapse ALL (79%, 9-36 months after diagnosis), but rare in very early relapse ALL (&lt;9 months, 9%). A marked chemotherapy-exposure signature was detected for mutations in early relapse ALL but not in very early ALL or AML relapse, in line with different mechanisms of relapse. Longitudinal analyses could track residual leukemia cells, clonal drug responses, and the upcoming relapse. These results highlight that KMT2A-r ALL and AML evade therapy differently and provide new insights into the mechanisms of relapse in this highly lethal form of pediatric acute leukemia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-06-12T09:30:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008198","title":"Aneuploidy in Pancreatic Cancer","description":"Aneuploidy in Pancreatic Cancer","abstract":"Aneuploidy in Pancreatic Cancer","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-06-12T14:06:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008199","title":"Detection of human brain cancers using genomic and immune cell characterization of cerebrospinal fluid through CSF-BAM","description":"Detection of human brain cancers using genomic and immune cell characterization of cerebrospinal fluid through CSF-BAM","abstract":"Detection of human brain cancers using genomic and immune cell characterization of cerebrospinal fluid through CSF-BAM","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-06-12T19:56:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008200","title":"Single-Gene vs. Panel Sequencing in Advanced HR+/HER2− Breast Cancer","description":"Background: Hormone receptor-positive (HR+)/HER2-negative (HER2−) breast cancer is the most common subtype of breast cancer, with biomarker-driven therapies improving outcomes. Liquid biopsies, which analyze circulating tumor DNA (ctDNA), are increasingly essential in clinical management, offering a minimally invasive approach to assess somatic alterations and guide therapy decisions. However, the choice of assay directly affects clinical utility and global access to validated testing platforms remains inconsistent. To address these challenges, this study aimed to compare the performance of single-gene and panel-based sequencing for detecting PIK3CA mutations in HR+/HER2− breast cancer and evaluate the added value of broader genomic profiling in guiding treatment decisions.\n\nPatients and methods: We conducted a prospective, multicenter study comparing our previously established SiMSen-Seq (SSS) assay, a single-gene method targeting PIK3CA hotspot mutations, with the AVENIO ctDNA Expanded assay, enriching for 77 clinically relevant cancer genes. Additionally, tumor fractions were estimated with mFAST-SeqS by assessing chromosomal aneuploidy. We analyzed 161 plasma samples collected from 146 patients with HR+/HER2− advanced breast cancer before starting a new line of palliative therapy.\n\nResults: High concordance (92.6%) was observed between SSS and AVENIO for PIK3CA mutation detection, with accurate variant allele frequency (VAF) quantification confirmed by Bland-Altman analysis and linear mixed-effects modeling. AVENIO identified additional PIK3CA mutations in 19% of samples as well as other actionable alterations, including ESR1 mutations (17.5%) and PI3K pathway alterations (40.6%). Panel sequencing improved the interpretation of negative liquid biopsy results by integrating tumor fraction and VAF metrics.\n\nConclusions: Panel sequencing assays such as AVENIO provide broader genomic coverage, enhance the detection of actionable mutations and refine the interpretation of negative liquid biopsy findings. These findings support the integration of comprehensive ctDNA profiling into routine clinical practice for HR+/HER2− advanced breast cancer while highlighting the need for improved assay accessibility and expanded genomic targets.\n","abstract":"Background: Hormone receptor-positive (HR+)/HER2-negative (HER2−) breast cancer is the most common subtype of breast cancer, with biomarker-driven therapies improving outcomes. Liquid biopsies, which analyze circulating tumor DNA (ctDNA), are increasingly essential in clinical management, offering a minimally invasive approach to assess somatic alterations and guide therapy decisions. However, the choice of assay directly affects clinical utility and global access to validated testing platforms remains inconsistent. To address these challenges, this study aimed to compare the performance of single-gene and panel-based sequencing for detecting PIK3CA mutations in HR+/HER2− breast cancer and evaluate the added value of broader genomic profiling in guiding treatment decisions.\n\nPatients and methods: We conducted a prospective, multicenter study comparing our previously established SiMSen-Seq (SSS) assay, a single-gene method targeting PIK3CA hotspot mutations, with the AVENIO ctDNA Expanded assay, enriching for 77 clinically relevant cancer genes. Additionally, tumor fractions were estimated with mFAST-SeqS by assessing chromosomal aneuploidy. We analyzed 161 plasma samples collected from 146 patients with HR+/HER2− advanced breast cancer before starting a new line of palliative therapy.\n\nResults: High concordance (92.6%) was observed between SSS and AVENIO for PIK3CA mutation detection, with accurate variant allele frequency (VAF) quantification confirmed by Bland-Altman analysis and linear mixed-effects modeling. AVENIO identified additional PIK3CA mutations in 19% of samples as well as other actionable alterations, including ESR1 mutations (17.5%) and PI3K pathway alterations (40.6%). Panel sequencing improved the interpretation of negative liquid biopsy results by integrating tumor fraction and VAF metrics.\n\nConclusions: Panel sequencing assays such as AVENIO provide broader genomic coverage, enhance the detection of actionable mutations and refine the interpretation of negative liquid biopsy findings. These findings support the integration of comprehensive ctDNA profiling into routine clinical practice for HR+/HER2− advanced breast cancer while highlighting the need for improved assay accessibility and expanded genomic targets.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-10-13T15:49:34.063823+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008201","title":"Inflammatory microenvironment impairs the therapeutic effect of daratumumab-lenalidomide in multiple myeloma","description":"Daratumumab and lenalidomide (DR) combination therapy has improved outcomes in multiple myeloma (MM), but some patients still experience poor responses. To understand the factors influencing treatment resistance, we performed single-cell RNA sequencing on bone marrow samples from 21 newly diagnosed MM patients enrolled in the IFM2017-03 trial, classifying them as complete responders (CR, n=11) or non-/poor responders (NR, n=10). NR patients exhibited pro-inflammatory bone marrow microenvironment (BME) characterized by elevated cytokine signaling. Classical and Nonclassical monocytes in NR patients displayed gene expression signals associated with impaired phagocytosis and interferon-associated monocytes upregulated NF-kB-related genes, while CD54dim NK cells in NR patients expressed lower levels of CD16, a marker associated with antibody-dependent cellular cytotoxicity. Furthermore, tumor cells from NR patients also showed enhanced NF-kB activation, which was correlated with increased inflammatory gene expression and poor prognosis. A random forest model based on 34 NF-kB-related genes accurately distinguished CR from NR patients (AUC = 0.96), and a refined model using the top eight genes maintained strong predictive power for bone marrow (AUC = 0.92) and peripheral blood samples (AUC = 0.77). These findings suggest that an inflamed BME and NF-kB signaling contribute to DR resistance, offering potential targets for overcoming poor responses.","abstract":"Daratumumab and lenalidomide (DR) combination therapy has improved outcomes in multiple myeloma (MM), but some patients still experience poor responses. To understand the factors influencing treatment resistance, we performed single-cell RNA sequencing on bone marrow samples from 21 newly diagnosed MM patients enrolled in the IFM2017-03 trial, classifying them as complete responders (CR, n=11) or non-/poor responders (NR, n=10). NR patients exhibited pro-inflammatory bone marrow microenvironment (BME) characterized by elevated cytokine signaling. Classical and Nonclassical monocytes in NR patients displayed gene expression signals associated with impaired phagocytosis and interferon-associated monocytes upregulated NF-kB-related genes, while CD54dim NK cells in NR patients expressed lower levels of CD16, a marker associated with antibody-dependent cellular cytotoxicity. Furthermore, tumor cells from NR patients also showed enhanced NF-kB activation, which was correlated with increased inflammatory gene expression and poor prognosis. A random forest model based on 34 NF-kB-related genes accurately distinguished CR from NR patients (AUC = 0.96), and a refined model using the top eight genes maintained strong predictive power for bone marrow (AUC = 0.92) and peripheral blood samples (AUC = 0.77). These findings suggest that an inflamed BME and NF-kB signaling contribute to DR resistance, offering potential targets for overcoming poor responses.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-07-02T14:35:27.821785+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008202","title":"RE_NanoSeq___Panbody_Evaluation_of_Somatic_Mutagenesis_in_LFS","description":"Panbody evaluation of somatic driver mutations in individuals with LFS using Targeted NanoSeq","abstract":"Panbody evaluation of somatic driver mutations in individuals with LFS using Targeted NanoSeq","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008203","title":"Impact_of_chemotherapy_on_the_male_germline___Targeted_NanoSeq","description":"This work aims to study how chemotherapy alters the mutation burden and clonal landscape in the male germline under different treatment regimens.","abstract":"As men age, the risk of pathogenic mutations in sperm increases, elevating the chances of having a child with a developmental disorder or cancer syndrome. It has been found that chemotherapy can sometimes cause hypermutation in sperm. However the degree and consistency with which chemotherapy has this effect is poorly understood. In this study we will sequence the sperm of men before and after chemotherapy treatment to detect what changes have occurred in their sperm mutational landscape.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008204","title":"Addenbrookes_Paediatric_Tumour_G17228_Wellcome_Core_RNA","description":"This child was diagnosed and succumbed to a stage 4S Neuroblastoma, these usually have an extremely good prognosis however in this case, uniquely presented with aggressive disease. This presents us with the opportunity to establish if the stage 4S disease was metastatic or had synchronous primary tumours, as well as analysis regarding the genetic relationship between normal and tumour.  Bulk RNA study.","abstract":"This child was diagnosed and succumbed to a stage 4S Neuroblastoma, these usually have an extremely good prognosis however in this case, uniquely presented with aggressive disease. This presents us with the opportunity to establish if the stage 4S disease was metastatic or had synchronous primary tumours, as well as analysis regarding the genetic relationship between normal and tumour.  Bulk RNA study","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008205","title":"Shaping the Genetic Landscape of Northeast India","description":"The genetic landscape of South Asia is intriguing. In a vast geographical region like India, mostly genes follow geography. Moreover, at neighbouring regions like East and Southeast Asia, language is the major denominator of the genes. However, these are not just the two alternatives, in many geographical pockets, ethnicity plays a stronger role than either of these. Being a crossroad of South and Southeast Asia, the Himalayan region is mostly populated by the people speaking the Trans-Himalayan language. Archaeological and anthropological studies suggest migration and cultural diffusion in this region with the Tibetan plateau in the North. To understand this complex pattern, we have performed a fine-grained genetic analysis of the major Mizo population and its various clans living at the Himalayan geography. We have investigated 110 individuals belonging to seven different clans of Mizo people for hundred thousand of autosomal markers. In contrast to the East and Southeast Asian genetic landscape, our results suggested that the fine-scaled genetic structure of Northeast India is much more complex and mixture of interplay between languages, ethnicity and geography. Allelic frequency-based analyses indicated that a novel Trans-Himalayan ancestry unite all the populations of this region.","abstract":"The genetic landscape of South Asia is intriguing. In a vast geographical region like India, mostly genes follow geography. Moreover, at neighbouring regions like East and Southeast Asia, language is the major denominator of the genes. However, these are not just the two alternatives, in many geographical pockets, ethnicity plays a stronger role than either of these. Being a crossroad of South and Southeast Asia, the Himalayan region is mostly populated by the people speaking the Trans-Himalayan language. Archaeological and anthropological studies suggest migration and cultural diffusion in this region with the Tibetan plateau in the North. To understand this complex pattern, we have performed a fine-grained genetic analysis of the major Mizo population and its various clans living at the Himalayan geography. We have investigated 110 individuals belonging to seven different clans of Mizo people for hundred thousand of autosomal markers. In contrast to the East and Southeast Asian genetic landscape, our results suggested that the fine-scaled genetic structure of Northeast India is much more complex and mixture of interplay between languages, ethnicity and geography. Allelic frequency-based analyses indicated that a novel Trans-Himalayan ancestry unite all the populations of this region.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008206","title":"DERMATLAS__Schwannoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Schwannomas.","abstract":" Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Schwannomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008207","title":"DERMATLAS__Schwannoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Schwannoma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Schwannoma.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008208","title":"DERMATLAS__Superficial_angiomyxoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Superficial angiomyxoma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Superficial angiomyxoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008209","title":"DERMATLAS__Superficial_angiomyxoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Superficial angiomyxoma.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are Superficial angiomyxoma.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008210","title":"Distinct Neurovascular Gene Regulatory Landscapes Link Small Vessel Disease and Alzheimer’s Risk, Revealing Immune and Vascular Genetic Contributions and Potential Therapeutic Targets","description":"Cerebral small vessel disease (SVD) is frequently comorbid with Alzheimer’s disease (AD) and vascular brain endothelial cells (BECs) are enriched for the expression of genes associated with AD genetic risk. However, the gene regulatory landscapes of neurovascular cells and their intersection with genetic risk for disease remains unexplored. Here we have generated gene regulomes for human BECs, mural cells and other brain cell types to show that AD heritability is primarily immune-related and that it shows modest enrichment in BECs. By contrast, genetic risk for SVD is enriched across cells of the neurovascular unit, including astrocytes. Enhancer-to-gene interactomes implicate amyloid processes in both AD and SVD, though the risk genes are mostly distinct for the two disorders. Motifs for putative partners of lineage transcription factors in microglia and BECs were enriched for AD and SVD variants at genes linked to disease pathways. Gene prioritization and enrichment analyses further identified potential repurposable drugs for AD. Our findings highlight novel regulatory mechanisms and therapeutic targets within the neurovascular system.","abstract":"Cerebral small vessel disease (SVD) is frequently comorbid with Alzheimer’s disease (AD) and vascular brain endothelial cells (BECs) are enriched for the expression of genes associated with AD genetic risk. However, the gene regulatory landscapes of neurovascular cells and their intersection with genetic risk for disease remains unexplored. Here we have generated gene regulomes for human BECs, mural cells and other brain cell types to show that AD heritability is primarily immune-related and that it shows modest enrichment in BECs. By contrast, genetic risk for SVD is enriched across cells of the neurovascular unit, including astrocytes. Enhancer-to-gene interactomes implicate amyloid processes in both AD and SVD, though the risk genes are mostly distinct for the two disorders. Motifs for putative partners of lineage transcription factors in microglia and BECs were enriched for AD and SVD variants at genes linked to disease pathways. Gene prioritization and enrichment analyses further identified potential repurposable drugs for AD. Our findings highlight novel regulatory mechanisms and therapeutic targets within the neurovascular system.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008211","title":"Mutation_burden_in_the_female_germline___RE_NanoSeq","description":"This work aims to quantify mutation burden directly from oocytes, demonstrating mutation accumulation in female germ cells.","abstract":"As humans age mutations accumulate in all cells, including reproductive cell types such as spermatogonia and oocytes. Mutation rates in these cell types have previous been inferred from family trio studies of de novo mutations. The introduction of duplex sequencing methods such as NanoSeq have recently enabled accurate sequence of non-clonal cell types, including sperm, directly validating male mutation rate. Here we apply NanoSeq to oocytes to directly quantify mutations in the female germline. ","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008212","title":"Segmental_cherry_angioma_case","description":"Cherry angiomas are common benign blood vessel growths on the skin. In this study we characterise mutational profile of a cherry angioma and adjacent skin biopsied from a patient with multiple lesions with segmental presentation.  ","abstract":"Cherry angiomas are common benign blood vessel growths on the skin. In this study we characterise mutational profile of a cherry angioma and adjacent skin biopsied from a patient with multiple lesions with segmental presentation.  ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-06-23T09:37:25+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008213","title":"Multimodal Spatial-Omics Reveal Co-Evolution of Alveolar Progenitors and Proinflammatory Niches in Progression of Lung Precursor Lesions","description":"The co-evolution and interactions of different cell subsets in progression of precursor lesions to lung adenocarcinoma (LUAD) are incompletely understood. We generated spatial transcriptomic maps of 56 human precursor lesions and LUADs from 25 patients and of an independent cohort of 36 lesions from 19 patients, analyzing a total of 486,519 spots and 5.4 million cells. We identify region-specific expression programs that distinguish precursors from LUADs. Spatially-resolved clonal architectures reveal patient-specific heterogeneity in evolution of precursors to LUADs. We find epithelial alveolar progenitors expressing tumor-associated meta-programs and residing in niches enriched with proinflammatory IL1B high macrophages. Epithelial-proinflammatory niches are prevalent in precursor lesions but become less frequent in LUADs. These niches are conserved in mice and promote alveolar progenitor growth. Targeting inflammation alone or in combination with immune checkpoint blockade in precancerous phase reduces alveolar progenitors. Epithelial-inflammatory niches are stage-specific, shape early LUAD development and represent promising targets for interception.","abstract":"The co-evolution and interactions of different cell subsets in progression of precursor lesions to lung adenocarcinoma (LUAD) are incompletely understood. We generated spatial transcriptomic maps of 56 human precursor lesions and LUADs from 25 patients and of an independent cohort of 36 lesions from 19 patients, analyzing a total of 486,519 spots and 5.4 million cells. We identify region-specific expression programs that distinguish precursors from LUADs. Spatially-resolved clonal architectures reveal patient-specific heterogeneity in evolution of precursors to LUADs. We find epithelial alveolar progenitors expressing tumor-associated meta-programs and residing in niches enriched with proinflammatory IL1B high macrophages. Epithelial-proinflammatory niches are prevalent in precursor lesions but become less frequent in LUADs. These niches are conserved in mice and promote alveolar progenitor growth. Targeting inflammation alone or in combination with immune checkpoint blockade in precancerous phase reduces alveolar progenitors. Epithelial-inflammatory niches are stage-specific, shape early LUAD development and represent promising targets for interception.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008214","title":"PMBCL IRF4 study","description":"Disease-defining signatures in lymphomas, driven by intricate molecular mechanisms, have advanced molecular taxonomies, refined classification, and may guide clinical management; however, the role of these signatures in driving disease hallmarks including subtype-specific organotropism remains largely unexplored. Primary mediastinal large B-cell lymphoma (PMBCL) is an exemplary lymphoma characterized by disease manifestations in the thymic niche, unique genetic alterations and immune escape. Here, we identified IRF4-C99R mutations uniquely occurring in PMBCL through mutational meta-analysis of large-scale datasets. Our functional studies, integrating multi-omics approaches with genome editing in PMBCL cells, revealed that IRF4-C99R contributes to a differentiation block phenotype. Specifically, we showed that IRF4-C99R reduces its binding to the ISRE motif within PRDM1, which encodes a key transcriptional regulator of B-cell differentiation, resulting in decreased PRDM1 expression. Additionally, IRF4-C99R suppresses TNIK, a key IFNγ pathway regulator, by impairing ISRE motif binding, thereby reducing IFNγ signaling and increasing thymus and activation-regulated chemokine (TARC) expression, which drives TARC-mediated chemotaxis of T regulatory cells. We also revealed that IRF4-C99R upregulates Ephrin Type-B Receptor 1 (EPHB1) through non-canonical AICE motif binding, and showed that overexpression of EPHB1 in an immunocompetent syngeneic lymphoma model influenced organotropism to favor thymic localization, without affecting tumor burden in other organs. IRF4-C99R mutation-induced phenotypes were validated in primary PMBCL tissues using single-nuclei RNA sequencing, confirming that the molecular mechanisms observed in vitro align with the pathophysiology of PMBCL in patients. Together, these findings demonstrate how a single genetic mutation orchestrates the coordinated regulation of hallmark traits including thymus-specific tropism in PMBCL.","abstract":"Disease-defining signatures in lymphomas, driven by intricate molecular mechanisms, have advanced molecular taxonomies, refined classification, and may guide clinical management; however, the role of these signatures in driving disease hallmarks including subtype-specific organotropism remains largely unexplored. Primary mediastinal large B-cell lymphoma (PMBCL) is an exemplary lymphoma characterized by disease manifestations in the thymic niche, unique genetic alterations and immune escape. Here, we identified IRF4-C99R mutations uniquely occurring in PMBCL through mutational meta-analysis of large-scale datasets. Our functional studies, integrating multi-omics approaches with genome editing in PMBCL cells, revealed that IRF4-C99R contributes to a differentiation block phenotype. Specifically, we showed that IRF4-C99R reduces its binding to the ISRE motif within PRDM1, which encodes a key transcriptional regulator of B-cell differentiation, resulting in decreased PRDM1 expression. Additionally, IRF4-C99R suppresses TNIK, a key IFNγ pathway regulator, by impairing ISRE motif binding, thereby reducing IFNγ signaling and increasing thymus and activation-regulated chemokine (TARC) expression, which drives TARC-mediated chemotaxis of T regulatory cells. We also revealed that IRF4-C99R upregulates Ephrin Type-B Receptor 1 (EPHB1) through non-canonical AICE motif binding, and showed that overexpression of EPHB1 in an immunocompetent syngeneic lymphoma model influenced organotropism to favor thymic localization, without affecting tumor burden in other organs. IRF4-C99R mutation-induced phenotypes were validated in primary PMBCL tissues using single-nuclei RNA sequencing, confirming that the molecular mechanisms observed in vitro align with the pathophysiology of PMBCL in patients. Together, these findings demonstrate how a single genetic mutation orchestrates the coordinated regulation of hallmark traits including thymus-specific tropism in PMBCL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008215","title":"Clinically Actionable Genomic and Transcriptomic Landscape of Advanced Neuroendocrine Neoplasms","description":"Epithelial neuroendocrine neoplasms (NENs) rare a rare and heterogeneous group of malignancies with limited treatment options. Comprehensive molecular characterization may reveal novel therapeutic opportunities for these clinically challenging tumors. We performed whole-genome/exome and transcriptome sequencing in 168 patients with advanced NENs from diverse anatomic origins, followed by evaluation of real-world outcomes associated with molecularly guided interventions. Our analysis revealed substantial molecular heterogeneity across advanced NENs, including distinct genetic profiles between low- and high-grade tumors and alterations specific to particular tissues of origin. In total, 144 patients (85.7%) received molecularly guided treatment recommendations. Our outcome data underscore the clinical utility of broad molecular profiling for patients with advanced NENs who have exhausted standard treatment options.","abstract":"Epithelial neuroendocrine neoplasms (NENs) rare a rare and heterogeneous group of malignancies with limited treatment options. Comprehensive molecular characterization may reveal novel therapeutic opportunities for these clinically challenging tumors. We performed whole-genome/exome and transcriptome sequencing in 168 patients with advanced NENs from diverse anatomic origins, followed by evaluation of real-world outcomes associated with molecularly guided interventions. Our analysis revealed substantial molecular heterogeneity across advanced NENs, including distinct genetic profiles between low- and high-grade tumors and alterations specific to particular tissues of origin. In total, 144 patients (85.7%) received molecularly guided treatment recommendations. Our outcome data underscore the clinical utility of broad molecular profiling for patients with advanced NENs who have exhausted standard treatment options.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS00001008216","title":"HCA_Genotyping_Adult_Teichmann_DNA_Managed_Access","description":"This project involves a genotyping dataset generated using the UK Biobank Axiom™ Array Kit from donor samples provided by the Cambridge Biorepository for Translational Medicine (CBTM). The dataset includes high-quality genome-wide array data suitable for a broad range of research applications in genomics and translational medicine.","abstract":"The array platform provides comprehensive coverage of common and low-frequency genetic variants across the genome, making this dataset a valuable resource for studies aiming to investigate the relationship between genetic variation and other molecular layers, such as transcriptomics, epigenomics, or proteomics. Researchers can leverage this dataset to explore genetic associations with disease phenotypes, identify expression quantitative trait loci (eQTLs), integrate multi-omics data, or perform fine-mapping and variant annotation in the context of functional genomics. This resource supports efforts to better understand the biological mechanisms underlying complex traits and diseases, and to advance precision medicine through the integration of genomic data with other biological and clinical information.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008217","title":"PEACE lung - Whole exome multiregion sequencing data","description":"PEACE lung - Whole exome multiregion sequencing data","abstract":"PEACE lung - Whole exome multiregion sequencing data","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-06-27T17:27:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008218","title":"Oncogenic and immunological targets for matched therapy of pediatric blood cancer patients: Dutch iTHER study experience","description":null,"abstract":"Over the past ten years, institutional and national molecular tumor boards have been implemented for relapsed or refractory pediatric cancer to prioritize targeted drugs for individualized treatment based on actionable oncogenic lesions, including the Dutch iTHER platform. Hematological malignancies form a minority in precision medicine studies. Here, we report on 56 iTHER leukemia/lymphoma patients for which we considered cell surface markers and oncogenic aberrations as actionable events, supplemented with ex vivo drug sensitivity for six patients. Prior to iTHER registration, 34% of the patients had received allogeneic hematopoietic cell transplantation (HCT) and 18% CAR-T therapy. For 51 patients (91%), a sample with sufficient tumor percentage (≥20%), required for comprehensive diagnostic testing, was obtained. Up to 10 oncogenic actionable events were prioritized in 49/51 patients and immunotherapy targets were identified in all profiled patients. Targeted treatment(s) based on the iTHER advice were given to 24 of 51 patients (47%), including immunotherapy in 17 patients, a targeted drug matching an oncogenic aberration in 12 patients, and a drug based on ex vivo drug sensitivity in one patient, resulting in objective responses and a bridge to HCT in the majority of the patients. In conclusion, comprehensive profiling of relapsed/refractory hematological malignancies showed multiple oncogenic and immunotherapy targets for a precision medicine approach, which requires multidisciplinary expertise to prioritize the best treatment options for this rare, heavily pre-treated, pediatric population.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-03T09:09:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008219","title":"Modelling_selective_vulnerability_of_C9orf72_ALS","description":"Modelling selective vulnerability of C9orf72 ALS","abstract":"Patient derived induced pluripotent lines (iPSC) lines will be used to model the molecular and cellular vulnerability of C9orf72 hexanucleotide repeat extension associated Amyotrophic lateral sclerosis (ALS).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008220","title":"Molecular characterisation of paediatric PDX cells before and after 3D RASTRUM bioprinting","description":"This dataset is a part of the publication and contains source data for comparative analysis of the molecular (TSO500, RNAseq) characteristics between patient-derived xenograft (PDX) cells from high-risk paediatric neuroblastoma and sarcoma models before and after 3D bioprinting using RASTRUM Bioprinter.","abstract":"This dataset is a part of the publication and contains source data for comparative analysis of the molecular (TSO500, RNAseq) characteristics between patient-derived xenograft (PDX) cells from high-risk paediatric neuroblastoma and sarcoma models before and after 3D bioprinting using RASTRUM Bioprinter.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-04T08:17:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008221","title":"Epigenetic age deceleration reflects fitness improvements following a six-month endurance exercise intervention","description":"Epigenetic clocks are emerging as promising biomarkers of biological aging, yet their sensitivity to short-term interventions remains unclear. This pilot study investigates whether the GrimAge clock can capture the effects of a six-month cycling-based endurance exercise training intervention, with cardiorespiratory fitness (VO₂ max) and body composition as primary outcomes. We enrolled 42 adults aged 35-65, of whom 38 completed the study and 33 adhered to the protocol (&gt;66% adherence). Participants demonstrated significant improvements in VO₂ max (+20%, P &lt; 0.001) and body composition (P &lt; 0.001). High-quality epigenetic data preprocessing yielded highly reproducible GrimAge estimates (&lt; 2 months measurement error), which strongly correlated with chronological age (R² = 0.86, P &lt; 0.001). On average, GrimAge decreased by 7.44 months relative to the expected trajectory (P = 0.012), reflecting improvements in VO₂ max (R² = 0.27, P = 0.002) but not body composition changes. Notably, GrimAge changes strongly correlated with fluctuations in leukocyte composition, particularly neutrophil fraction (R² = 0.74, P &lt; 0.001). Adjusting for leukocyte composition improved consistency in GrimAge changes, aligning them with additional intervention outcomes and explaining up to 81% of variance. These findings demonstrate that GrimAge is responsive to short-term endurance training, serving as a meaningful biomarker of improved cardiorespiratory fitness, while also capturing immune system variability. This study supports the use of GrimAge in evaluating longevity interventions and highlights the importance of accounting for leukocyte composition in epigenetic aging research.","abstract":"Epigenetic clocks are emerging as promising biomarkers of biological aging, yet their sensitivity to short-term interventions remains unclear. This pilot study investigates whether the GrimAge clock can capture the effects of a six-month cycling-based endurance exercise training intervention, with cardiorespiratory fitness (VO₂ max) and body composition as primary outcomes. We enrolled 42 adults aged 35-65, of whom 38 completed the study and 33 adhered to the protocol (&gt;66% adherence). Participants demonstrated significant improvements in VO₂ max (+20%, P &lt; 0.001) and body composition (P &lt; 0.001). High-quality epigenetic data preprocessing yielded highly reproducible GrimAge estimates (&lt; 2 months measurement error), which strongly correlated with chronological age (R² = 0.86, P &lt; 0.001). On average, GrimAge decreased by 7.44 months relative to the expected trajectory (P = 0.012), reflecting improvements in VO₂ max (R² = 0.27, P = 0.002) but not body composition changes. Notably, GrimAge changes strongly correlated with fluctuations in leukocyte composition, particularly neutrophil fraction (R² = 0.74, P &lt; 0.001). Adjusting for leukocyte composition improved consistency in GrimAge changes, aligning them with additional intervention outcomes and explaining up to 81% of variance. These findings demonstrate that GrimAge is responsive to short-term endurance training, serving as a meaningful biomarker of improved cardiorespiratory fitness, while also capturing immune system variability. This study supports the use of GrimAge in evaluating longevity interventions and highlights the importance of accounting for leukocyte composition in epigenetic aging research.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-08T12:29:16+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008222","title":"Relapse CHL study","description":"Classical Hodgkin Lymphoma (CHL) is characterized by a complex tumor microenvironment (TME) that supports disease progression. While immune cell recruitment by Hodgkin and Reed–Sternberg (HRS) cells is well-documented, the role of non-malignant B cells in relapse remains unclear. Using single-cell RNA sequencing (scRNA-seq) on paired diagnostic and relapsed CHL samples, we identified distinct shifts in B cell populations, particularly an enrichment of naïve B cells and a reduction of memory B cells in early-relapse compared to late-relapse and newly diagnosed CHL. The enrichment of naïve B cells in early relapse biopsies was confirmed in independent validation cohorts using scRNA-seq and immunohistochemistry. Notably, naïve B cells in early-relapse samples exhibited high expression of LGALS9, an immunosuppressive molecule known to interact with T cell immunoglobulin and mucin domain 3 (TIM-3) on regulatory T cells (Tregs). Cell-cell interaction analysis revealed the importance of interactions between LGALS9+ naïve B cells and TIM-3+ Tregs in the early-relapse setting. Spatial analysis by imaging mass cytometry confirmed close proximity of LGALS9+ naïve B cells with TIM-3⁺ CD4⁺ T cells and HRS cells, pointing to their role in shaping an immunosuppressive niche. Our findings highlight a previously unrecognized population of LGALS9⁺ naïve B cells with immunoregulatory potential in early-relapse CHL and provide new insights into the spatial and transcriptional architecture of the relapsed TME in CHL.","abstract":"Classical Hodgkin Lymphoma (CHL) is characterized by a complex tumor microenvironment (TME) that supports disease progression. While immune cell recruitment by Hodgkin and Reed–Sternberg (HRS) cells is well-documented, the role of non-malignant B cells in relapse remains unclear. Using single-cell RNA sequencing (scRNA-seq) on paired diagnostic and relapsed CHL samples, we identified distinct shifts in B cell populations, particularly an enrichment of naïve B cells and a reduction of memory B cells in early-relapse compared to late-relapse and newly diagnosed CHL. The enrichment of naïve B cells in early relapse biopsies was confirmed in independent validation cohorts using scRNA-seq and immunohistochemistry. Notably, naïve B cells in early-relapse samples exhibited high expression of LGALS9, an immunosuppressive molecule known to interact with T cell immunoglobulin and mucin domain 3 (TIM-3) on regulatory T cells (Tregs). Cell-cell interaction analysis revealed the importance of interactions between LGALS9+ naïve B cells and TIM-3+ Tregs in the early-relapse setting. Spatial analysis by imaging mass cytometry confirmed close proximity of LGALS9+ naïve B cells with TIM-3⁺ CD4⁺ T cells and HRS cells, pointing to their role in shaping an immunosuppressive niche. Our findings highlight a previously unrecognized population of LGALS9⁺ naïve B cells with immunoregulatory potential in early-relapse CHL and provide new insights into the spatial and transcriptional architecture of the relapsed TME in CHL.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008223","title":"Stratton__RE_NanoSeq___Identification_of_Early_Life_Exposures_in_Paediatric_Colonic_Crypts_of_Healthy_Individuals","description":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. This study will evaluate mutational burdens and signatures in paediatric colonic epithelium from non-cancerous donors.","abstract":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. This study will evaluate mutational burdens and signatures in paediatric colonic epithelium from non-cancerous donors.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008224","title":"Sequencing_oesophageal_epithelium_structures","description":"High depth targeted sequencing of structures in human oesophageal epithelium","abstract":"High depth targeted sequencing of structures in human oesophageal epithelium","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008225","title":"H3K27me3-mediated epigenetic repression regulates neuroblastoma development and contributes to biological heterogeneity","description":"Characterization of the H3K27me3 repressive landscape in neuroblastoma tumor samples.","abstract":"Characterization of the H3K27me3 repressive landscape in neuroblastoma tumor samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-14T14:45:50+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008226","title":"Copy number profile of ctDNA in ovarian cancer patients","description":"This study analyzes the copy number profiles from circulating tumor DNA (ctDNA) in plasma samples withdrawn from ovarian cancer patients, in a subset of samples from the MITO16A clinical trial.","abstract":"This study analyzes the copy number profiles from circulating tumor DNA (ctDNA) in plasma samples withdrawn from ovarian cancer patients, in a subset of samples from the MITO16A clinical trial.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-16T13:03:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008227","title":"Capturing disease severity in LIS1-lissencephaly reveals proteostasis dysregulation in patient-derived forebrain organoids","description":"Lissencephaly is a developmental cortical malformation characterized by reduced to absent gyri and a disorganized cortex, often leading to severe impairments in affected individuals and a reduced life expectancy. Heterozygous mutations in the LIS1 gene, encoding a regulator of the microtubule motor dynein, cause lissencephaly with different clinical severities. While the clinical disease spectrum correlates with the degree of lissencephaly, location and type of mutation may not. We leveraged forebrain-type organoids from LIS1-lissencephaly patients, diagnosed with mild, moderate or severe lissencephaly to investigate, in a cytoarchitecture and multi-omics approach, how the severity degree in patients might relate to specific mutations in the LIS1 gene. We questioned which processes during cortical development might be differentially affected by severity grade, and whether they could be pharmacologically targeted. We found alterations in neurodevelopment often with a severity-dependent gradient. Specifically, we identified alterations of the cytoarchitecture, progenitor cell homeostasis and neurogenesis. Particularly important disease-linked molecular mechanisms were microtubule destabilization, WNT-signaling, and perturbed cadherin- and unfolded protein-binding. Some mechanisms exhibited a severity-dependent gradient, or were specific to a severe grade. We present strategies to reverse phenotypic changes in LIS1-patient organoids, and an in silico approach with therapeutic potential. Thus, we show that different LIS1-severity grades can be recapitulated in vitro, that there is a direct link between the phenotype and genotype, that organoid-based disease modeling can identify molecular underpinnings of malformations of cortical development and that organoids provide a valid platform to develop and test therapeutic strategies.","abstract":"Lissencephaly is a developmental cortical malformation characterized by reduced to absent gyri and a disorganized cortex, often leading to severe impairments in affected individuals and a reduced life expectancy. Heterozygous mutations in the LIS1 gene, encoding a regulator of the microtubule motor dynein, cause lissencephaly with different clinical severities. While the clinical disease spectrum correlates with the degree of lissencephaly, location and type of mutation may not. We leveraged forebrain-type organoids from LIS1-lissencephaly patients, diagnosed with mild, moderate or severe lissencephaly to investigate, in a cytoarchitecture and multi-omics approach, how the severity degree in patients might relate to specific mutations in the LIS1 gene. We questioned which processes during cortical development might be differentially affected by severity grade, and whether they could be pharmacologically targeted. We found alterations in neurodevelopment often with a severity-dependent gradient. Specifically, we identified alterations of the cytoarchitecture, progenitor cell homeostasis and neurogenesis. Particularly important disease-linked molecular mechanisms were microtubule destabilization, WNT-signaling, and perturbed cadherin- and unfolded protein-binding. Some mechanisms exhibited a severity-dependent gradient, or were specific to a severe grade. We present strategies to reverse phenotypic changes in LIS1-patient organoids, and an in silico approach with therapeutic potential. Thus, we show that different LIS1-severity grades can be recapitulated in vitro, that there is a direct link between the phenotype and genotype, that organoid-based disease modeling can identify molecular underpinnings of malformations of cortical development and that organoids provide a valid platform to develop and test therapeutic strategies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-16T14:59:42+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008228","title":"HCA_Genotyping_Adult_Teichmann_DNA","description":"This project involves a genotyping dataset generated using the UK Biobank Axiom™ Array Kit from donor samples provided by the Cambridge Biorepository for Translational Medicine (CBTM). The dataset includes high-quality genome-wide array data suitable for a broad range of research applications in genomics and translational medicine.","abstract":"The array platform provides comprehensive coverage of common and low-frequency genetic variants across the genome, making this dataset a valuable resource for studies aiming to investigate the relationship between genetic variation and other molecular layers, such as transcriptomics, epigenomics, or proteomics. Researchers can leverage this dataset to explore genetic associations with disease phenotypes, identify expression quantitative trait loci (eQTLs), integrate multi-omics data, or perform fine-mapping and variant annotation in the context of functional genomics. This resource supports efforts to better understand the biological mechanisms underlying complex traits and diseases, and to advance precision medicine through the integration of genomic data with other biological and clinical information.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-17T13:49:48+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008229","title":"Neoantigen Peptides derived from V(D)J-recombined Immunoglobulins Drive Outgrowth of Cytolytic CD8+ T-cells","description":null,"abstract":"Non-Hodgkin Lymphomas (NHL) are a diverse group of solid tumors that primarily originate fromlymphoid tissues, with B-cell derived (B-) NHL accounting for up to 90% of all cases. B-NHL tumorsresult from B-cells that have undergone V(D)J gene rearrangements and express immunoglobulinscontaining sequences not encoded by germline DNA. As such, these sequences may lead to thegeneration of neoantigens. These neoantigens might induce autologous CD8+ T-cell responses, that inpatients with B-NHL tumors might have failed to effectively reject the tumor. Recent studies haveidentified CD4+ T-cells specific to neoantigen peptides in mantle-cell lymphoma. This studyinvestigates the potential of utilizing existing neoantigen-specific CD8+ T-cells for immunotherapy. Weanalyzed 34 B-NHL tumor samples from children for the presence of immunoglobulin-derivedneoantigen peptides. We identified these using V(D)J recombination prediction software and HLA-A2binding, and synthesized nonamer peptides for functional testing. Our results demonstrate that B-NHLpatients possess CD8+ T-cell clones with specificity to immunoglobulin-derived neoantigens, capableof inducing cytotoxic responses. These findings suggest that targeting neoantigen-specific CD8+ T-cellsmay offer a promising therapeutic strategy for various B-NHL subtypes, including Burkitt lymphoma,diffuse large B-cell lymphoma, and primary mediastinal large B-cell lymphoma.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-18T11:59:19+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008230","title":"CRISPR_Screening_of_Brazilian_Acral_Melanoma_Cell_Lines","description":"Perform CRISPR Screening in acral melanoma cell lines, using a genome-wide gRNA library, aiming to identify genes essential for their survival and proliferation. The results will aid the identification of key genes and pathways implicated in acral melanoma progression, paving the way to understand the disease and offer potential targets for precision therapies to this subtype of melanoma.  ","abstract":"Acral melanoma, a subtype of melanoma characterized by its occurrence on palms, soles, and beneath the nails, presents unique challenges in diagnosis and treatment due to its distinct genetic and environmental factors. Despite recent advancements in targeted therapies for melanoma, the efficacy of treatments in acral melanoma remains limited, emphasizing the urgent need for a deeper understanding of its genetic landscape. CRISPR-based functional genomics screening has emerged as a powerful tool for uncovering genetic dependencies and potential therapeutic targets in various cancers. In this project, we present the results of CRISPR screening performed on acral melanoma cell lines to identify genes essential for cell survival and proliferation collectively termed “fitness\". Through this screening approach, we aim to elucidate the molecular mechanisms underlying the pathogenesis of acral melanoma and identify novel therapeutic vulnerabilities. Our findings reveal key genetic drivers and pathways implicated in acral melanoma progression, offering potential targets for the development of precision therapies tailored to this aggressive subtype of melanoma. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-18T15:51:02+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008231","title":"PDX_models_from_Latin_America_Xenofiltered_WES","description":"Acral melanoma (AM) is a subtype of cutaneous melanoma that occurs on glabrous skin of the hands and feet (palms, soles and nail apparatus) and which is relatively more common in non-European descent populations such as those of Latin America. Compared to other subtypes, it is poorly studied and experimental models that faithfully reproduce human AM features are urgently needed. We report the generation and preliminary characterisation of a collection of patient-derived xenografts of acral melanomas (AM-PDX) from Latin-American patients. PDX came from Brazilian and Mexican patients cared for at the Instituto Nacional de Câncer (INCA) and the Instituto Nacional de Cancerologia (INCan). The majority of the samples are acral lentiginous melanomas, ulcerated, with &gt; 4mm Breslow depth and &gt; 2 mitosis / mm2. Samples were mechanically fragmented and subcutaneously implanted in NSG mice and then collected for molecular analysis.","abstract":"Acral melanoma (AM) is a subtype of cutaneous melanoma that occurs on glabrous skin of the hands and feet (palms, soles and nail apparatus) and which is relatively more common in non-European descent populations such as those of Latin America. Compared to other subtypes, it is poorly studied and experimental models that faithfully reproduce human AM features are urgently needed. We report the generation and preliminary characterisation of a collection of patient-derived xenografts of acral melanomas (AM-PDX) from Latin-American patients. PDX came from Brazilian and Mexican patients cared for at the Instituto Nacional de Câncer (INCA) and the Instituto Nacional de Cancerologia (INCan). The majority of the samples are acral lentiginous melanomas, ulcerated, with &gt; 4mm Breslow depth and &gt; 2 mitosis / mm2. Samples were mechanically fragmented and subcutaneously implanted in NSG mice and then collected for molecular analysis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-22T13:36:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008232","title":"PDX_models_from_Latin_America_RNAseq_Xenofiltered","description":"Acral melanoma (AM) is a subtype of cutaneous melanoma that occurs on glabrous skin of the hands and feet (palms, soles and nail apparatus) and which is relatively more common in non-European descent populations such as those of Latin America. Compared to other subtypes, it is poorly studied and experimental models that faithfully reproduce human AM features are urgently needed. We report the generation and preliminary characterisation of a collection of patient-derived xenografts of acral melanomas (AM-PDX) from Latin-American patients. PDX came from Brazilian and Mexican patients cared for at the Instituto Nacional de Câncer (INCA) and the Instituto Nacional de Cancerologia (INCan). The majority of the samples are acral lentiginous melanomas, ulcerated, with &gt; 4mm Breslow depth and &gt; 2 mitosis / mm2. Samples were mechanically fragmented and subcutaneously implanted in NSG mice and then collected for molecular analysis. ","abstract":"Acral melanoma (AM) is a subtype of cutaneous melanoma that occurs on glabrous skin of the hands and feet (palms, soles and nail apparatus) and which is relatively more common in non-European descent populations such as those of Latin America. Compared to other subtypes, it is poorly studied and experimental models that faithfully reproduce human AM features are urgently needed. We report the generation and preliminary characterisation of a collection of patient-derived xenografts of acral melanomas (AM-PDX) from Latin-American patients. PDX came from Brazilian and Mexican patients cared for at the Instituto Nacional de Câncer (INCA) and the Instituto Nacional de Cancerologia (INCan). The majority of the samples are acral lentiginous melanomas, ulcerated, with &gt; 4mm Breslow depth and &gt; 2 mitosis / mm2. Samples were mechanically fragmented and subcutaneously implanted in NSG mice and then collected for molecular analysis. ","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-22T13:42:13+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008233","title":"Cold Ischemia Study","description":"This study aimed to evaluate the impact of cold ischemia time on the expression of cancer-related genes, particularly those involved in hypoxia, apoptosis, and epithelial-to-mesenchymal transition (EMT). We performed RNA sequencing on 54 normal colon mucosa samples from nine patients undergoing colorectal cancer surgeries, freezing samples at predefined intervals ranging from 0 to 60 minutes. A total of 44 differentially expressed genes (DEGs) (p &lt; 0.05) were identified when comparing samples frozen immediately (T0) with those frozen after 60 minutes (T5). ","abstract":"This study aimed to evaluate the impact of cold ischemia time on the expression of cancer-related genes, particularly those involved in hypoxia, apoptosis, and epithelial-to-mesenchymal transition (EMT). We performed RNA sequencing on 54 normal colon mucosa samples from nine patients undergoing colorectal cancer surgeries, freezing samples at predefined intervals ranging from 0 to 60 minutes. A total of 44 differentially expressed genes (DEGs) (p &lt; 0.05) were identified when comparing samples frozen immediately (T0) with those frozen after 60 minutes (T5). ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-23T08:34:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008234","title":"Analysis of the co-occurrence of LOY and CHIP in Alzheimer's disease patients and control individuals using whole-exome sequencing (WES)","description":"We performed deep whole-exome sequencing of FACS-isolated CD4+ T lymphocytes, NK and myeloid cells from men with AD and controls exhibiting either LOY or retention of Y chromosome (ROY). We found 39 sequence variants in known (canonical) myeloid driver genes of clonal hematopoiesis (MD-CH) and known lymphoid driver genes (LD-CH), and maximally 14 (35%) of these could co-exist with LOY within the same clone. We further describe 192 unknown drivers of clonal hematopoiesis (UD-CH), which were markedly enriched in AD-LOY individuals (odds ratio=4.8, Benjamini-Hochberg-adjusted p=0.041), and over 20% of these variants were protein-truncating. In myeloid cells, the total burden of all detected drivers correlated with the percentage of LOY cells (Spearman ρ=0.52, adjusted p=0.00041).","abstract":"We performed deep whole-exome sequencing of FACS-isolated CD4+ T lymphocytes, NK and myeloid cells from men with AD and controls exhibiting either LOY or retention of Y chromosome (ROY). We found 39 sequence variants in known (canonical) myeloid driver genes of clonal hematopoiesis (MD-CH) and known lymphoid driver genes (LD-CH), and maximally 14 (35%) of these could co-exist with LOY within the same clone. We further describe 192 unknown drivers of clonal hematopoiesis (UD-CH), which were markedly enriched in AD-LOY individuals (odds ratio=4.8, Benjamini-Hochberg-adjusted p=0.041), and over 20% of these variants were protein-truncating. In myeloid cells, the total burden of all detected drivers correlated with the percentage of LOY cells (Spearman ρ=0.52, adjusted p=0.00041).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-25T08:18:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008235","title":"WGS_of_Somatic_Mosaicism_of_BRCA1_Methylation_in_Malignant_and_Nonmalignant_Breast_Tissue","description":"WGS of Somatic Mosaicism of BRCA1 Methylation in Malignant and Nonmalignant Breast Tissue","abstract":"WGS of Somatic Mosaicism of BRCA1 Methylation in Malignant and Nonmalignant Breast Tissue","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-25T09:04:04+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008236","title":"EMseq_of_Somatic_Mosaicism_of_BRCA1_Methylation_in_Malignant_and_Nonmalignant_Breast_Tissue","description":"EMseq of Somatic Mosaicism of BRCA1 Methylation in Malignant and Nonmalignant Breast Tissue","abstract":"EMseq of Somatic Mosaicism of BRCA1 Methylation in Malignant and Nonmalignant Breast Tissue","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-25T09:05:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008237","title":"CMML_Bulk_WGS","description":"Whole genome sequencing to determine HSC phylogeny in MDS and clonal haematopoiesis patients undergoing treatment with hypomethylating agents.","abstract":"Whole genome sequencing to determine HSC phylogeny in MDS and clonal haematopoiesis patients undergoing treatment with hypomethylating agents.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-25T09:20:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008238","title":"ATACseq of primary fibroblasts and iPSC-derived endoderm cells in CPRF patients with LSD1 mutations and healthy controls","description":"Primary fibroblasts or iPSC-derived endoderm cells from two CPRF patients carrying distinct heterozygous point mutations in histone demethylase LSD1/KDM1A and their healthy fathers were expanded and split into two cell culture wells and independently passaged twice before cell collection. Nuclei were isolated from the two biological replicates of each individual-derived fibroblasts and used for bulk ATAC-seq library preparation. Libraries were sequenced in paired-end mode on Illumina NextSeq 500. ","abstract":"genotype design;family based design;disease state design;biological replicate;compound treatment design;cell type comparison design","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-25T11:28:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008239","title":"Carcinoma of Unknown Primary (CUP): A comparison across tissue and liquid biomarkers (CUP-COMP) study","description":"The Carcinoma of Unknown Primary (CUP): A comparison across tissue and liquid biomarkers (CUP-COMP) study (NCT: NCT04750109) was sponsored by The Christie NHS Foundation Trust and funded by Innovate UK. Data generated include: A) Whole genome sequencing* of paired germline blood and tumour tissue B) Whole genome sequencing *of germline blood only C) Next-generation sequencing of circulating tumour DNA (FoundationOne Liquid CDX) D) Next-generation sequencing of tumour tissue (FoudationOne CDX) *Whole genome sequencing - germline sample at 30x coverage and somatic sample at 75x coverage performed by Illumina NovaSeq 6000 instrument in the 150bp PE read mode.","abstract":"The Carcinoma of Unknown Primary (CUP): A comparison across tissue and liquid biomarkers (CUP-COMP) study (NCT: NCT04750109) was sponsored by The Christie NHS Foundation Trust and funded by Innovate UK. Data generated include: A) Whole genome sequencing* of paired germline blood and tumour tissue B) Whole genome sequencing *of germline blood only C) Next-generation sequencing of circulating tumour DNA (FoundationOne Liquid CDX) D) Next-generation sequencing of tumour tissue (FoudationOne CDX) *Whole genome sequencing - germline sample at 30x coverage and somatic sample at 75x coverage performed by Illumina NovaSeq 6000 instrument in the 150bp PE read mode.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-25T11:28:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008240","title":"Gene expression profiling by RNAseq of multiple cell types derived from patients with LSD1 mutations and healthy controls, and in isogenic cell lines with LSD1 mutation introduced by CRISPR-Cas9","description":"Cell lines (fibroblasts, reprogrammed from them hiPSCs and differentiated from hiPSCs endoderm, mesoderm and neuronal cells) derived from two male CPRF patients carrying distinct LSD1 mtuations and their healthy fathers as controls were subjected to gene expression analysis by bulk RNAseq to identify mis-regulated genes. Some cell lines were subject to treatment with HDAC inhibitor valproic acid (VPA) or DMSO as controls and also underwent RNAseq analysis. Two isogenic LSD1 mutant hiPSC lines with CRISPR-edited Family B LSD1 mutation were also used for RNAseq analysis (after endoderm differentiation, with or without VPA treatment).","abstract":"genotype design;disease state design;biological replicate;compound treatment design;family based design;cell type comparison design","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-25T14:08:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008241","title":"Osteosarcoma_multiregion_characterisation___WGS","description":"Characterisation of osteosarcoma across multiple regions of primary tumours, local recurrences and metastases using whole genome sequencing, methylation and transcriptomics. This study contains the WGS data.","abstract":"Osteosarcoma tumours typically have highly rearranged genomes. In this study, we investigate the mechanisms driving genomic instability and formation of complex rearrangements, as well as the phenotypic impact of these alterations on tumour biology. ","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-25T14:19:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008242","title":"ChIP-seq profiling of H3K4me1 and H3K27ac in iPSCs and iPSC-derived endoderm cells in CPRF patients with LSD1 mutations and healthy controls","description":"LSD1 patient (children) and control (healthy fathers) derived iPSCs and endoderm differentiated cells were expanded and harvested for ChIP-seq experiment following the procedure described in Trovato et al, PMID: 39214979. Cells were cross-linked in PFA, sonicated and soluble fractions were collected for IP with H3K4me1 or H3K27ac antibodies. Sequencing libraries were prepared using the NEBNext Ultra II DNA Library Preparation Kit (New England Biolabs) and sequenced on Illumina NextSeq 500 (75 bp in single-end mode).","abstract":"replicate design;family based design;disease state design;cell type comparison design;genotype design;binding site identification design","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-25T14:22:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008243","title":"Osteosarcoma_multiregion_characterisation___Methylation","description":"Characterisation of osteosarcoma across multiple regions of primary tumours, local recurrences and metastases using whole genome sequencing, methylation and transcriptomics. This study contains the methylation data.","abstract":"Osteosarcoma tumours typically have highly rearranged genomes. In this study, we investigate the mechanisms driving genomic instability and formation of complex rearrangements, as well as the phenotypic impact of these alterations on tumour biology. ","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-25T14:32:05+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008244","title":"Macrophage_ontogeny_LCMB","description":"The origins of different tissue macrophages will be characterized by mutational analyses of WGS sequencing data created from LCMB WGS libraries. Samples have been sourced from Newcastle","abstract":"The origins of different tissue macrophages will be characterized by mutational analyses of WGS sequencing data created from LCMB WGS libraries. Samples have been sourced from Newcastle","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008245","title":"OMKar","description":"The whole genome karyotype refers to the sequence of large chromosomal segments that make up an individuals genotype. karyotype analysis, which includes descriptions of aneuploidies and other rearrangements is crucial for understanding genetic risk factors, for diagnosis, treatment decisions, and genetic counseling linked to constitutional disorders. The current karyotyping standard is based on microscopic examination of chromosomes, a complex process that requires high expertise and offers Mb scale resolution. Optical Genome Mapping (OGM) technology can identify large DNA lesions in a cost-effective manner. In this paper, we developed OMKar, a method that uses OGM data to create a virtual karyotype. OMKar processes Structural (SV) and Copy Number (CN) Variants as inputs and encodes them into a compact breakpoint graph. It recomputes copy numbers using Integer Linear Programming to maintain CN balance and then identifies constrained Eulerian paths representing entire donor chromosomes. In tests using 38 whole genome simulations of constitutional disorders, OMKar reconstructed the karyotype with 88% precision and 95% recall on SV concordance and 95% Jaccard score on CN concordance. We applied OMKar to 50 prenatal, 41 postnatal, and 63 parental samples from ten different sites. OMKar reconstructed the correct karyotype in 144 out of 154 samples, covering 25 of 25 aneuploidies, 32 of 32 balanced translocations, and 72 of 82 unbalanced variations. Detected constitutional disorders included Cri-du-chat, Wolf-Hirschhorn, Prader-Willi deletions, Down, and Turner syndromes. Importantly, it identified a plausible genetic mechanism for five cases of constitutional disorder that were not detected by other technologies. Together, these results demonstrate the robustness of OMKar for OGM-based karyotyping.","abstract":"The whole genome karyotype refers to the sequence of large chromosomal segments that make up an individuals genotype. karyotype analysis, which includes descriptions of aneuploidies and other rearrangements is crucial for understanding genetic risk factors, for diagnosis, treatment decisions, and genetic counseling linked to constitutional disorders. The current karyotyping standard is based on microscopic examination of chromosomes, a complex process that requires high expertise and offers Mb scale resolution. Optical Genome Mapping (OGM) technology can identify large DNA lesions in a cost-effective manner. In this paper, we developed OMKar, a method that uses OGM data to create a virtual karyotype. OMKar processes Structural (SV) and Copy Number (CN) Variants as inputs and encodes them into a compact breakpoint graph. It recomputes copy numbers using Integer Linear Programming to maintain CN balance and then identifies constrained Eulerian paths representing entire donor chromosomes. In tests using 38 whole genome simulations of constitutional disorders, OMKar reconstructed the karyotype with 88% precision and 95% recall on SV concordance and 95% Jaccard score on CN concordance. We applied OMKar to 50 prenatal, 41 postnatal, and 63 parental samples from ten different sites. OMKar reconstructed the correct karyotype in 144 out of 154 samples, covering 25 of 25 aneuploidies, 32 of 32 balanced translocations, and 72 of 82 unbalanced variations. Detected constitutional disorders included Cri-du-chat, Wolf-Hirschhorn, Prader-Willi deletions, Down, and Turner syndromes. Importantly, it identified a plausible genetic mechanism for five cases of constitutional disorder that were not detected by other technologies. Together, these results demonstrate the robustness of OMKar for OGM-based karyotyping.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-28T20:53:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008246","title":"Influence of age on molecular changes and treatment stratification in multimodal glioblastoma therapy","description":"Background: The increasing life expectancy has led to a rise in high-grade gliomas, particularly in patients of older age. The impact of chronological age, associated molecular changes and contributing factors on therapy response, progression-free survival (PFS) and overall survival (OS) remain uncertain.\nMethods: Between January 1st, 2016, and December 31th, 2021, patients with glioblastoma IDH-wt (CNS WHO grade 4) were included. RNA- and T-cell receptor sequencing was performed in a subset of patients. Primary outcome parameters were extent of resection (EOR), progression free- and overall survival. Multivariate analysis was performed to identify independent predictors of survival. \nResults: A total of 286 patients were included. The mean age was 66.4 years. Chronological age did not correlate with overall survival (r=0.12). With age, tumor immune composition changed towards macrophages with M2 phenotype and decreased numbers of CD8+ and neutrophiles. Aging related genes were not enriched. Beyond 69.5 years of age, despite similar PFS (p=0.0783), OS (p&lt;0.0001) was significantly shorter, compared to younger patients. Extent of resection and adjuvant radiochemotherapy were significant predictors of OS (p&lt;0.0001). No difference in PFS and OS was found between younger and older patients treated with maximal safe resection, followed by concomitant RT and chemotherapy and adjuvant chemotherapy.\nConclusions: This study suggests that age alone should not be the sole determinant in therapeutic decision-making for glioblastoma patients. Gross total resection and adjuvant therapy, tailored to individual clinical status, significantly impact survival outcomes. Patient-specific treatment strategies are important to minimize undertreatment and optimize therapeutic outcomes in older patients.\n","abstract":"Background: The increasing life expectancy has led to a rise in high-grade gliomas, particularly in patients of older age. The impact of chronological age, associated molecular changes and contributing factors on therapy response, progression-free survival (PFS) and overall survival (OS) remain uncertain.\nMethods: Between January 1st, 2016, and December 31th, 2021, patients with glioblastoma IDH-wt (CNS WHO grade 4) were included. RNA- and T-cell receptor sequencing was performed in a subset of patients. Primary outcome parameters were extent of resection (EOR), progression free- and overall survival. Multivariate analysis was performed to identify independent predictors of survival. \nResults: A total of 286 patients were included. The mean age was 66.4 years. Chronological age did not correlate with overall survival (r=0.12). With age, tumor immune composition changed towards macrophages with M2 phenotype and decreased numbers of CD8+ and neutrophiles. Aging related genes were not enriched. Beyond 69.5 years of age, despite similar PFS (p=0.0783), OS (p&lt;0.0001) was significantly shorter, compared to younger patients. Extent of resection and adjuvant radiochemotherapy were significant predictors of OS (p&lt;0.0001). No difference in PFS and OS was found between younger and older patients treated with maximal safe resection, followed by concomitant RT and chemotherapy and adjuvant chemotherapy.\nConclusions: This study suggests that age alone should not be the sole determinant in therapeutic decision-making for glioblastoma patients. Gross total resection and adjuvant therapy, tailored to individual clinical status, significantly impact survival outcomes. Patient-specific treatment strategies are important to minimize undertreatment and optimize therapeutic outcomes in older patients.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-07-29T21:36:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008247","title":"Tumor and Circulating Biomarkers in FLC","description":"Fibrolamellar hepatocellular carcinoma (FLC) is a very rare primary liver cancer occurring in young adult with a normal liver. Currently, no serum tumor biomarker is available in clinical practice as serum AFP level is not increased in these patients. This study aims to identify tumor biomarkers specific of fibrolamellar hepatocellular carcinoma also detectable in the blood of the patients in order to use it as a non-invasive biomarkers for the diagnosis of fibrolamellar hepatocellular carcinoma and the follow-up under treatment.","abstract":"Fibrolamellar hepatocellular carcinoma (FLC) is a very rare primary liver cancer occurring in young adult with a normal liver. Currently, no serum tumor biomarker is available in clinical practice as serum AFP level is not increased in these patients. This study aims to identify tumor biomarkers specific of fibrolamellar hepatocellular carcinoma also detectable in the blood of the patients in order to use it as a non-invasive biomarkers for the diagnosis of fibrolamellar hepatocellular carcinoma and the follow-up under treatment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008248","title":"PDX_models_from_Latin_America_WGS_","description":"Acral melanoma (AM) is a subtype of cutaneous melanoma that occurs on glabrous skin of the hands and feet (palms, soles and nail apparatus) and which is relatively more common in non-European descent populations such as those of Latin America. Compared to other subtypes, it is poorly studied and experimental models that faithfully reproduce human AM features are urgently needed. We report the generation and preliminary characterisation of a collection of patient-derived xenografts of acral melanomas (AM-PDX) from Latin-American patients. PDX came from Brazilian and Mexican patients cared for at the Instituto Nacional de Câncer (INCA) and the Instituto Nacional de Cancerologia (INCan). The majority of the samples are acral lentiginous melanomas, ulcerated, with &gt; 4mm Breslow depth and &gt; 2 mitosis / mm2. Samples were mechanically fragmented and subcutaneously implanted in NSG mice and then collected for molecular analysis. ","abstract":"Acral melanoma (AM) is a subtype of cutaneous melanoma that occurs on glabrous skin of the hands and feet (palms, soles and nail apparatus) and which is relatively more common in non-European descent populations such as those of Latin America. Compared to other subtypes, it is poorly studied and experimental models that faithfully reproduce human AM features are urgently needed. We report the generation and preliminary characterisation of a collection of patient-derived xenografts of acral melanomas (AM-PDX) from Latin-American patients. PDX came from Brazilian and Mexican patients cared for at the Instituto Nacional de Câncer (INCA) and the Instituto Nacional de Cancerologia (INCan). The majority of the samples are acral lentiginous melanomas, ulcerated, with &gt; 4mm Breslow depth and &gt; 2 mitosis / mm2. Samples were mechanically fragmented and subcutaneously implanted in NSG mice and then collected for molecular analysis. ","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008249","title":"Integrative Multi-Omics and Drug Sensitivity Profiling Reveals Potential Predictive Biomarkers in Pediatric Solid Tumors from the INFORM Registry","description":"Cure rates for childhood malignancies using established therapy protocols have increased to an average of 80% but have reached a plateau. Moreover, survival rates are particularly low for some pediatric tumors (such as high-risk Group3 medulloblastomas, osteosarcomas, Ewing sarcomas, high-risk neuroblastomas and high-grade gliomas) and dismal for patients with relapsed malignancies. A functional drug response profiling platform for pediatric solid and brain tumors has been established within the INFORM program to identify patient-specific vulnerabilities, biomarkers and unravel molecular mechanisms associated with drug response profiles for clinical translation. Here, we perform a multi-omics analysis using drug sensitivity profiles, genomic, and transcriptomic data of 81 pediatric solid tumor samples. The integrative analysis revealed two multi-omics signatures with high drug sensitivity predictivity. One signature highlighted neuroblastoma samples with sensitivity to navitoclax (a BCL-2 family inhibitor). A second signature was significantly specific to a subset of Wilms tumors harboring the SIX1 (Q177R) hotspot mutation, which had high expression of MGAM, PTPN14, STAT4 and KDM2B and high sensitivity to MEK inhibitors. A patient-specific causal interaction network analysis elucidated the potential biological mechanism of action between MEK inhibitors and the SIX1 mutation in n = 6 Wilms tumor samples.","abstract":"Cure rates for childhood malignancies using established therapy protocols have increased to an average of 80% but have reached a plateau. Moreover, survival rates are particularly low for some pediatric tumors (such as high-risk Group3 medulloblastomas, osteosarcomas, Ewing sarcomas, high-risk neuroblastomas and high-grade gliomas) and dismal for patients with relapsed malignancies. A functional drug response profiling platform for pediatric solid and brain tumors has been established within the INFORM program to identify patient-specific vulnerabilities, biomarkers and unravel molecular mechanisms associated with drug response profiles for clinical translation. Here, we perform a multi-omics analysis using drug sensitivity profiles, genomic, and transcriptomic data of 81 pediatric solid tumor samples. The integrative analysis revealed two multi-omics signatures with high drug sensitivity predictivity. One signature highlighted neuroblastoma samples with sensitivity to navitoclax (a BCL-2 family inhibitor). A second signature was significantly specific to a subset of Wilms tumors harboring the SIX1 (Q177R) hotspot mutation, which had high expression of MGAM, PTPN14, STAT4 and KDM2B and high sensitivity to MEK inhibitors. A patient-specific causal interaction network analysis elucidated the potential biological mechanism of action between MEK inhibitors and the SIX1 mutation in n = 6 Wilms tumor samples.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-08-01T11:26:01+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008250","title":"Genome-wide methylation detection and episignature analysis using PacBio long-read sequencing","description":null,"abstract":null,"study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-08-01T13:33:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008251","title":"Hepatoblastoma tumoroid biobank as a key resource for tumour genetics","description":null,"abstract":"Hepatoblastoma (HB) is a paediatric liver malignancy, originating from liver precursor cells. Over 90% of the cases have a mutation in exon 3 of CTNNB1. In this study we present a fully genetically characterised HB tumoroid biobank to allow study into disease progression and clonal evolution in vitro.  \nWe established a tumoroid biobank of 14 tumoroid lines from 9 different patients. All tumours and tumoroids were characterised using whole genome sequencing (WGS) and histology. Tumour and tumoroid samples show similarities on cell morphology and -catenin staining, indicating a large resemblance between tumour and tumoroid. We found the same pathogenic variant in CTNBB1 in HB samples and matching tumoroids. Furthermore, we observed similar copy number variants (CNVs) in tumour samples and matched tumoroids as well as similar mutations, albeit with a higer variant allele frequency (VAF), indicating a high tumour purity in vitro. Besides the driver mutation in CTNNB1, we also observed a high occurrence of variants in ARID1A, albeit single nucleotide variants (SNVs) or CNVs in 56% of patients. Additionally, we observed gains in MYC as described previously. In samples obtained before and after treatment, a clear increase in mutational load could be observed that was mainly attributed to a chemotherapy signature. In this study, we feature a set of 8 samples from the same patient,of which 6 samples were obtained after treatment. All samples carry a previously undescribed mutation in BCL6 and loss of ARID1A. The BCL6 mutation is located in the zinc finger domain of BCL6 and predicted to be pathogenic by Alphamissense. We also observed variation in mutations found in the different samples obtained at different locations from the same tumour. indicating a heterogeneous tumour where we select for different clones in different tumoroid samples. \nTaken together, this biobank allows us to study tumour development by the availability of samples both before and after treatment and clonal evolution of HB by studying up to 8 different samples from the same patient","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-08-04T07:27:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008252","title":"The_Little_Princess_Knowledge_Bank_EMseq","description":"We propose to build a genetic knowledge bank of Wilms tumour that integrates clinical outcome data with a genetic, epigenetic, and transcriptomic survey of 1,000 Wilms tumours.\nThe purpose of the knowledge bank is to serve as a community resource and to address the following specific questions about Wilms tumour: (1) Do genetic, epigenetic, or transcriptional features predict outcome and thus lend themselves to treatment stratification? (2) What are the genetic drivers of Wilms tumour, considering the entire histological spectrum of Wilms tumour including the most common subtypes classified as intermediate risk?","abstract":"We propose to build a genetic knowledge bank of Wilms tumour that integrates clinical outcome data with a genetic, epigenetic, and transcriptomic survey of 1,000 Wilms tumours.\nThe purpose of the knowledge bank is to serve as a community resource and to address the following specific questions about Wilms tumour: (1) Do genetic, epigenetic, or transcriptional features predict outcome and thus lend themselves to treatment stratification? (2) What are the genetic drivers of Wilms tumour, considering the entire histological spectrum of Wilms tumour including the most common subtypes classified as intermediate risk?","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008253","title":"Genomic_and_transcriptomic_changes_in_gliobastoma_","description":"Analysis of of copy number variation and  transcriptional consequences in glioblastoma\n","abstract":"Glioblastoma multiforme (GBM) is an aggressive type of brain tumour that is currently incurable. It is the most common type of primary malignant brain tumour in adults. GBM presents a high level of inter and intra tumour heterogeneity at genetic and transcriptional level. The project in collaboration with GBM-space aims at defining the clonal structure of GBM samples, identifying Copy number variations and their impact on tumour cell transcriptome and mechanism of expansion. ","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008254","title":"Colorectal Microenvironment Spatial Mapping","description":"In colorectal cancer (CRC), interactions between tumor and immune cells within the tumor microenvironment are critical drivers of tumorigenesis, immune evasion, prognosis, and therapeutic response. Therefore, a deeper understanding of the spatial organization of cancer and immune cells within the CRC microenvironment is urgently needed. In this study, we aimed to characterize distinct cell populations and patterns of spatial gene expression associated with CRC tumorigenesis and immune infiltration.\n\nSpatial transcriptomics (ST) was performed on CRC and adjacent normal tissues to investigate the patterns of gene expression. Integrative ST data and publicly available single-cell RNA sequencing (scRNA-seq) data analysis tools were used for data integration, dimension reduction, clustering, and differential expression analysis.\n\nThis study identified novel immunosuppressive cell populations and immune regulatory factors in CRC. Further functional validation of these findings will be essential to assess their potential as therapeutic targets.","abstract":"In colorectal cancer (CRC), interactions between tumor and immune cells within the tumor microenvironment are critical drivers of tumorigenesis, immune evasion, prognosis, and therapeutic response. Therefore, a deeper understanding of the spatial organization of cancer and immune cells within the CRC microenvironment is urgently needed. In this study, we aimed to characterize distinct cell populations and patterns of spatial gene expression associated with CRC tumorigenesis and immune infiltration.\n\nSpatial transcriptomics (ST) was performed on CRC and adjacent normal tissues to investigate the patterns of gene expression. Integrative ST data and publicly available single-cell RNA sequencing (scRNA-seq) data analysis tools were used for data integration, dimension reduction, clustering, and differential expression analysis.\n\nThis study identified novel immunosuppressive cell populations and immune regulatory factors in CRC. Further functional validation of these findings will be essential to assess their potential as therapeutic targets.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-08-06T14:02:32+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008255","title":"test","description":"test","abstract":"test","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008256","title":"Organ_maturation_in_preparation_for_birth__Peds_RFA__to_develop_a_tissue__resource_and_a_single_cell_atlas_of_organ_development_and_maturation_for__dissemination_among_the_scientific_and_clinical_community__RNA","description":"Knowledge about abnormal organ development is important to understand pathology and to develop novel treatment approaches for individuals with congenital and acquired disease. Most of our current understanding is based on examination of tissues from the embryo and early foetus, collected from women undergoing termination of pregnancy in the first trimester (third) of pregnancy. There is very little known about normal and abnormal organ development from a developmental perspective during the crucial last two-thirds of pregnancy when much remodelling of foetal tissues occurs. This study will generate a single-cell atlas of late-foetal lungs, blood, heart, bone and immune organs. \n","abstract":"Collaboration with Marko Nikolic to study gene expression and cellular heterogeneity changes in third trimester lung and blood tissue samples (samples obtained from UCLH and GOSH). The grant was awarded under the CZI paediatric grant\n","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-08-07T10:26:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008257","title":"Understanding_the_development_of_resident_memory_T_cells__Trm__in_the_human_small_intestine_using_integrative_multiomic_approaches__Adult_RNA","description":"Animal studies have demonstrated that resident memory T (Trm) cells provide enhanced protective responses to a broad array of tissue-tropic pathogens, thus making Trm cells promising targets for novel vaccination strategies. However, the biological pathways that enable the long-term survival of Trm cells are poorly understood in humans. Here, we will employ a unique human intestinal transplantation setting that allows us to study the retention of persistent T cells in the grafts and the temporal development of resident T-cell populations from recruited recipient T cells. We will integrate high resolution transcriptomics, epigenetics, proteomics and immune repertoire single-cell data from purified intestinal T cells. These single-cell multiomics approaches will uncover the diversity and differentiation of the T cell populations in the human intestine, allowing us to temporally resolve the generation and maintenance of gut resident T cells.\n","abstract":"Animal studies have demonstrated that resident memory T (Trm) cells provide enhanced protective responses to a broad array of tissue-tropic pathogens, thus making Trm cells promising targets for novel vaccination strategies. However, the biological pathways that enable the long-term survival of Trm cells are poorly understood in humans. Here, we will employ a unique human intestinal transplantation setting that allows us to study the retention of persistent T cells in the grafts and the temporal development of resident T-cell populations from recruited recipient T cells. We will integrate high resolution transcriptomics, epigenetics, proteomics and immune repertoire single-cell data from purified intestinal T cells. These single-cell multiomics approaches will uncover the diversity and differentiation of the T cell populations in the human intestine, allowing us to temporally resolve the generation and maintenance of gut resident T cells\n","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-08-07T12:54:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008258","title":"Whole genome sequencing of tumor samples from advanced pre-treated NSCLC patients recruited in a phase I/II single-arm trial utilising CVA21, an oncolytic coxsackie virus, in combination with pembrolizumab.","description":"Acquired or de novo resistance to immune checkpoint inhibitors occurs in the majority of advanced non-small cell lung cancers (NSCLC). There is an unmet need to improve outcomes for patients with this condition. Oncolytic viruses represent an attractive treatment approach due to their dual activity in inducing tumor cell lysis directly and potentially augmenting anti-tumor immunity. Here, we present the safety, efficacy and translational findings from a phase I/II single-arm trial utilising CVA21, an oncolytic coxsackie virus, in combination with pembrolizumab in patients with advanced pre-treated NSCLC. We performed paired biopsies pre- and post-treatment in 10 patients who received intravenous CVA21 and pembrolizumab, 8 of whom had prior treatment with immune checkpoint inhibitor (ICI) therapy. Whole genome sequencing and spatial proteomics were performed to comprehensively characterise the response to CVA21. Combination CVA21/pembrolizumab (anti PD-1) therapy was well tolerated with no serious treatment-related adverse events. Partial responses were seen in two patients with prior acquired anti-PD-1 resistance and disease stabilisation in 6 patients, giving a clinical benefit rate of 80%. High baseline tumor mutational burden and PD-L1 expression were observed in patients with better response to treatment. Interestingly, an increase in antigen presentation and CD8+ T cell infiltration was observed on treatment compared with baseline in patients with better progression-free survival. This study demonstrates the potential of CVA21 to modulate the immunogenicity of tumor cells and remodelling the tumor microenvironment, providing novel insights for patient selection for trials involving novel immunotherapeutic approaches.","abstract":"Acquired or de novo resistance to immune checkpoint inhibitors occurs in the majority of advanced non-small cell lung cancers (NSCLC). There is an unmet need to improve outcomes for patients with this condition. Oncolytic viruses represent an attractive treatment approach due to their dual activity in inducing tumor cell lysis directly and potentially augmenting anti-tumor immunity. Here, we present the safety, efficacy and translational findings from a phase I/II single-arm trial utilising CVA21, an oncolytic coxsackie virus, in combination with pembrolizumab in patients with advanced pre-treated NSCLC. We performed paired biopsies pre- and post-treatment in 10 patients who received intravenous CVA21 and pembrolizumab, 8 of whom had prior treatment with immune checkpoint inhibitor (ICI) therapy. Whole genome sequencing and spatial proteomics were performed to comprehensively characterise the response to CVA21. Combination CVA21/pembrolizumab (anti PD-1) therapy was well tolerated with no serious treatment-related adverse events. Partial responses were seen in two patients with prior acquired anti-PD-1 resistance and disease stabilisation in 6 patients, giving a clinical benefit rate of 80%. High baseline tumor mutational burden and PD-L1 expression were observed in patients with better response to treatment. Interestingly, an increase in antigen presentation and CD8+ T cell infiltration was observed on treatment compared with baseline in patients with better progression-free survival. This study demonstrates the potential of CVA21 to modulate the immunogenicity of tumor cells and remodelling the tumor microenvironment, providing novel insights for patient selection for trials involving novel immunotherapeutic approaches.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-08-08T07:38:49+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008259","title":"Whole exome sequencing data for paired non-serous endometrial and ovarian carcinomas from 27 patients with concurrent tumours. ","description":"Introduction: Concurrent non-serous endometrial and ovarian tumours are often managed clinically as two separate primary tumours, but almost all exhibit evidence of a genomic relationship.\n\nMethodology: This study investigates the extent of relatedness using whole exome sequencing, which was performed on paired non-serous endometrial and ovarian carcinomas from 27 patients with concurrent tumours in a cohort with detailed clinicopathological annotation. Four whole exome sequencing-derived parameters (mutation, mutational burden, mutational signatures and mutant allele tumour heterogeneity scores) were used to develop a novel unsupervised model for the assessment of genomic similarity to infer genomic relatedness of paired tumours.\n\nResults: This novel model demonstrated genomic relatedness across all four parameters in all tumour pairs. Mutations in PTEN, ARID1A, CTNNB1, KMT2D and PIK3CA occurred most frequently and 24 of 27 (89 %) tumour pairs shared identical mutations in at least one of these genes, with all pairs sharing mutations in a number of other genes. Ovarian endometriosis, CTNNB1 exon 3 mutation, and progression and death from disease were present across the similarity ranking. Mismatch repair deficiency was associated with less genomically similar pairs.\n\nDiscussion: Although there was diversity across the cohort, the presence of genomic similarity in all paired tumours supports the hypothesis that concurrent non-serous endometrial and ovarian carcinomas are genomically related and may have arisen from a common origin.\n\nKeywords: Co-existing; Concurrent; Endometrial carcinoma; Genomics; Mutation; Ovarian carcinoma; Paired tumours; Tumour mutational burden.","abstract":"Introduction: Concurrent non-serous endometrial and ovarian tumours are often managed clinically as two separate primary tumours, but almost all exhibit evidence of a genomic relationship.\n\nMethodology: This study investigates the extent of relatedness using whole exome sequencing, which was performed on paired non-serous endometrial and ovarian carcinomas from 27 patients with concurrent tumours in a cohort with detailed clinicopathological annotation. Four whole exome sequencing-derived parameters (mutation, mutational burden, mutational signatures and mutant allele tumour heterogeneity scores) were used to develop a novel unsupervised model for the assessment of genomic similarity to infer genomic relatedness of paired tumours.\n\nResults: This novel model demonstrated genomic relatedness across all four parameters in all tumour pairs. Mutations in PTEN, ARID1A, CTNNB1, KMT2D and PIK3CA occurred most frequently and 24 of 27 (89 %) tumour pairs shared identical mutations in at least one of these genes, with all pairs sharing mutations in a number of other genes. Ovarian endometriosis, CTNNB1 exon 3 mutation, and progression and death from disease were present across the similarity ranking. Mismatch repair deficiency was associated with less genomically similar pairs.\n\nDiscussion: Although there was diversity across the cohort, the presence of genomic similarity in all paired tumours supports the hypothesis that concurrent non-serous endometrial and ovarian carcinomas are genomically related and may have arisen from a common origin.\n\nKeywords: Co-existing; Concurrent; Endometrial carcinoma; Genomics; Mutation; Ovarian carcinoma; Paired tumours; Tumour mutational burden.","study_type":"Other","pubmed_ids":[38986422],"external_links":null,"is_released":true,"released_date":"2025-08-08T14:32:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008260","title":"Placental_genomics_EMseq","description":"The aim of this study is to define the mutational landscape of placentas.","abstract":"The aim of this study is to define the mutational landscape of placentas.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008261","title":"Mutational dynamics of triple negative breast cancer over neoadjuvant chemotherapy treatment reveal frequent whole genome duplication events","description":"Background\nTriple-negative breast cancer (TNBC) is associated with poor survival rate and high genomic instability, generating complex tumour genomes. However, the processes generating this complexity are poorly studied over time. Here, we study the temporal dynamics of TNBC somatic mutations, revealing major transitions in tumour genome evolution, from diagnostic biopsies, through treatment, to cancer remission or recurrence.\n\nMethods\nDeep whole exome sequencing and CUTseq, a reduced representation whole genome sequencing approach, were performed in parallel, to comprehensively identify short nucleotide variants (SNVs), copy number alterations (CNAs) and aneuploidies genome-wide. We profiled (N=74) tumour samples from 22 patients across the course of disease, including spatially diverse samples from many tumours, allowing us to observe the gain and loss of candidate driver variants over time.\n\nResults\nAs expected, tumour infiltrating lymphocyte (TIL) levels and residual cancer burden (RCB) score were negatively correlated, with good responses to neoadjuvant chemotherapy (NACT) seen in pre-treatment samples with high infiltration. In general, SNV mutational burden remained stable across disease progression and RCB classes. Recurrent SNVs across the cohort implicated several known TNBC driver genes in disease progression and response to treatment, with TP53, MICA, CYP2D6, BRCA1 and BRCA2 frequently altered. However, the presence of candidate driver SNVs in these genes often varied throughout a patient’s treatment, including the loss of those seen in a given driver gene in pre-treatment samples, but gain of novel variants in the same gene at later time points. Dramatic structural dynamics were seen in all tumours, including abundant CNA including chromosome arm aneuploidies seen in pre-treatment samples, followed by frequent loss of these alterations post-treatment, and their re-emergence at recurrence. Whole genome duplication (WGD) events appear to drive these dynamics, with a higher frequency of pre-treatment WGD seen in patients with the best response to NACT.\n\nConclusions\nComprehensive longitudinal profiling demonstrates the complex interplay of SNVs and copy number alterations during TNBC progression, leading to diverse evolutionary trajectories and patient outcomes. Complex mutational patterns emerge as important features during progression, with WGD events emerging as potential candidate biomarkers of response at both tumour establishment and recurrence.","abstract":"Background\nTriple-negative breast cancer (TNBC) is associated with poor survival rate and high genomic instability, generating complex tumour genomes. However, the processes generating this complexity are poorly studied over time. Here, we study the temporal dynamics of TNBC somatic mutations, revealing major transitions in tumour genome evolution, from diagnostic biopsies, through treatment, to cancer remission or recurrence.\n\nMethods\nDeep whole exome sequencing and CUTseq, a reduced representation whole genome sequencing approach, were performed in parallel, to comprehensively identify short nucleotide variants (SNVs), copy number alterations (CNAs) and aneuploidies genome-wide. We profiled (N=74) tumour samples from 22 patients across the course of disease, including spatially diverse samples from many tumours, allowing us to observe the gain and loss of candidate driver variants over time.\n\nResults\nAs expected, tumour infiltrating lymphocyte (TIL) levels and residual cancer burden (RCB) score were negatively correlated, with good responses to neoadjuvant chemotherapy (NACT) seen in pre-treatment samples with high infiltration. In general, SNV mutational burden remained stable across disease progression and RCB classes. Recurrent SNVs across the cohort implicated several known TNBC driver genes in disease progression and response to treatment, with TP53, MICA, CYP2D6, BRCA1 and BRCA2 frequently altered. However, the presence of candidate driver SNVs in these genes often varied throughout a patient’s treatment, including the loss of those seen in a given driver gene in pre-treatment samples, but gain of novel variants in the same gene at later time points. Dramatic structural dynamics were seen in all tumours, including abundant CNA including chromosome arm aneuploidies seen in pre-treatment samples, followed by frequent loss of these alterations post-treatment, and their re-emergence at recurrence. Whole genome duplication (WGD) events appear to drive these dynamics, with a higher frequency of pre-treatment WGD seen in patients with the best response to NACT.\n\nConclusions\nComprehensive longitudinal profiling demonstrates the complex interplay of SNVs and copy number alterations during TNBC progression, leading to diverse evolutionary trajectories and patient outcomes. Complex mutational patterns emerge as important features during progression, with WGD events emerging as potential candidate biomarkers of response at both tumour establishment and recurrence.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-08-15T15:16:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008262","title":"HCA_Embryo_Foetal_Dev_DNA","description":"Detailed genomic atlas of whole human embryos","abstract":"We propose to generate an in-depth single cell, spatial atlas and whole genome sequencing of human embryos during late organogenesis, between 6/11 post conception weeks (PCW). We will deploy genomics technologies to profile single cells from dissociated tissues and within intact tissue sections, and deploy cutting-edge computational methods to reconstruct, in silico, a three-dimensional atlas of the whole human embryo. Detailed single cell atlas of whole human embryos Deliverables: Complete whole embryo atlas datasets by high-throughput genomics profiling (single cell RNA-sequencing (scRNA-seq), single nuclear RNA-sequencing (snRNA-seq), and accessible chromatin sequencing (ATAC-seq)); and spatial transcriptomics (ST, e.g. 10x Genomics Visium), in situ sequencing (ISS) and multiplex smFISH analysis of tissue sections.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008264","title":"Peruvian Population Genomics: Unraveling the Genetic Landscape and Admixture Dynamics of Urban Populations","description":"Genome-wide study of human populations living in Peruvian urban areas","abstract":"Latin American populations exhibit high genetic and phenotypic diversity shaped by complex admixture histories yet remain underrepresented in genomic research. Here, we analyze genome-wide data from 432 urban individuals across 13 regions of Peru, including 346 newly genotyped from the Peruvian Genome Project. We revealed fine-scale population structure and demographic patterns shaped by both ancient and recent events. Indigenous American ancestries in urban individuals trace back to ancient north-south interactions consisted with archaeological records, while admixture events occurring within the last 8–10 generations involved sources already admixed between distinct ancestral lineages. Identity-by-descent analyses reveal sustained gene flow in southern Peru, while effective population size trends highlight demographic stability in Lima over the past 25 generations. Sex-biased admixture patterns suggest Indigenous ancestry contribution preferentially mediated by females. These findings offer a comprehensive view of Peru's genetic heritage, advancing our understanding of human genetic diversity and historical demographic processes in Latin America.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-08-21T05:29:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008265","title":"Genome-wide gene expression analysis following CRISPRi of transposable elements","description":"human induced pluripotent stem cells constitutely expressing the CRISPRi machinery were transduced with gRNAs targeting genomic regions of transposable elements (TEs), and differentiated to neural progenitor cells. The aim of the study was to annotate the function of these TEs in the context of early neurodevelopmental processes.","abstract":"genetic modification design","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-08-25T16:41:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008266","title":"Enzymatic_Methylation_sequencing_of_Outlier_rhabdomyosarcoma_tumour_tissue","description":"Whilst some genomic features of rhabdomyosarcoma are employed in diagnosis and risk stratification in current protocols, new genomic biomarker discovery has been frustrated by small study sample sizes, or necessary focus on a small number of genes/regions of interest.This study has coordinated a high quality and detailed clinical annotation of a cohort of samples, facilitating the identification of a cohort of clinical outliers and matched controls. These will undergo extensive whole genomic and transcriptomic sequencing to identify novel risk biomarkers and further delineate the genomic landscape of RMS.\n","abstract":"Whilst some genomic features of rhabdomyosarcoma are employed in diagnosis and risk stratification in current protocols, new genomic biomarker discovery has been frustrated by small study sample sizes, or necessary focus on a small number of genes/regions of interest.This study has coordinated a high quality and detailed clinical annotation of a cohort of samples, facilitating the identification of a cohort of clinical outliers and matched controls. These will undergo extensive whole genomic and transcriptomic sequencing to identify novel risk biomarkers and further delineate the genomic landscape of RMS.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008267","title":"Enzymatic_Methylation_sequencing_of_Outlier_rhabdomyosarcoma_tumour_tissue","description":"Whilst some genomic features of rhabdomyosarcoma are employed in diagnosis and risk stratification in current protocols, new genomic biomarker discovery has been frustrated by small study sample sizes, or necessary focus on a small number of genes/regions of interest.This study has coordinated a high quality and detailed clinical annotation of a cohort of samples, facilitating the identification of a cohort of clinical outliers and matched controls. These will undergo extensive whole genomic and transcriptomic sequencing to identify novel risk biomarkers and further delineate the genomic landscape of RMS.\n","abstract":"Whilst some genomic features of rhabdomyosarcoma are employed in diagnosis and risk stratification in current protocols, new genomic biomarker discovery has been frustrated by small study sample sizes, or necessary focus on a small number of genes/regions of interest.This study has coordinated a high quality and detailed clinical annotation of a cohort of samples, facilitating the identification of a cohort of clinical outliers and matched controls. These will undergo extensive whole genomic and transcriptomic sequencing to identify novel risk biomarkers and further delineate the genomic landscape of RMS.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008268","title":"Bulk_RNA_sequencing_of_Outlier_rhabdomyosarcoma_tumour_tissue","description":"Whilst some genomic features of rhabdomyosarcoma are employed in diagnosis and risk stratification in current protocols, new genomic biomarker discovery has been frustrated by small study sample sizes, or necessary focus on a small number of genes/regions of interest.This study has coordinated a high quality and detailed clinical annotation of a cohort of samples, facilitating the identification of a cohort of clinical outliers and matched controls. These will undergo extensive whole genomic and transcriptomic sequencing to identify novel risk biomarkers and further delineate the genomic landscape of RMS.\n","abstract":"Whilst some genomic features of rhabdomyosarcoma are employed in diagnosis and risk stratification in current protocols, new genomic biomarker discovery has been frustrated by small study sample sizes, or necessary focus on a small number of genes/regions of interest.This study has coordinated a high quality and detailed clinical annotation of a cohort of samples, facilitating the identification of a cohort of clinical outliers and matched controls. These will undergo extensive whole genomic and transcriptomic sequencing to identify novel risk biomarkers and further delineate the genomic landscape of RMS.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008269","title":"Spatial-temporal MPNST evolution","description":"Understanding the spatial and temporal dynamics of tumour evolution is crucial for determining the drivers of cancer progression. Here, we comprehensively profile a primary malignant peripheral nerve sheath tumour (MPNST) and its recurrence with a multi-omic and spatial approach at single-cell resolution. Leveraging the extensive heterogeneity in copy number aberrations (CNAs) as a native barcoding system, we fully resolve the evolutionary tree of this tumour revealing multi-furcations suggestive of ongoing chromosomal instability. We show gene dosage effects contribute to phenotypic diversity and are predominantly linear with the exception of FOS in a specific subclone. Using laser capture microdissection, we performed spatial lineage tracing in a human tumour, elucidating the relationship between local expansions and interactions between tumour cells and the microenvironment. Our study illustrates the power of integrating spatial multi-omics at both bulk and single-cell levels to dissect cancer evolution and link genotype to phenotype in detail. These findings offer insights into tumour development and demonstrate the potential of single-cell techniques to characterise individual spatial subclones.","abstract":"Understanding the spatial and temporal dynamics of tumour evolution is crucial for determining the drivers of cancer progression. Here, we comprehensively profile a primary malignant peripheral nerve sheath tumour (MPNST) and its recurrence with a multi-omic and spatial approach at single-cell resolution. Leveraging the extensive heterogeneity in copy number aberrations (CNAs) as a native barcoding system, we fully resolve the evolutionary tree of this tumour revealing multi-furcations suggestive of ongoing chromosomal instability. We show gene dosage effects contribute to phenotypic diversity and are predominantly linear with the exception of FOS in a specific subclone. Using laser capture microdissection, we performed spatial lineage tracing in a human tumour, elucidating the relationship between local expansions and interactions between tumour cells and the microenvironment. Our study illustrates the power of integrating spatial multi-omics at both bulk and single-cell levels to dissect cancer evolution and link genotype to phenotype in detail. These findings offer insights into tumour development and demonstrate the potential of single-cell techniques to characterise individual spatial subclones.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008270","title":"Whole_genome_sequencing_of_rhabdomyosarcoma_tumouroids","description":"The aim of this study is to investigate the genomic landscape of human cancer.\n","abstract":"Rhabdomyosarcoma is a paediatric soft tissue cancer arising from developing muscle. A subset of these tumours harbours a somatic fusion involving the FOXO1 gene, which strongly correlates with poor clinical outcomes and defines a molecularly high-risk group. These fusion-positive cancers are characterized by a gene expression profile resembling mature muscle cells, while fusion-negative tumours typically appear less differentiated.To better understand the cellular origins of lethality in fusion-negative rhabdomyosarcoma, we analysed single-cell transcriptomic profiles and validated our findings using nuclear RNA-sequencing, chromatin accessibility assays, spatial transcriptomics, functional perturbation studies, and external datasets. Our findings highlight a common high-risk cell state that transcends traditional subtype classifications in rhabdomyosarcoma and may inform future therapeutic targeting strategies.\n","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-08-28T10:58:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008271","title":"Single_cell_RNA_sequencing_of_rhabdomyosarcoma_tumour_tissue","description":"The aim of this study is to investigate the genomic landscape of human cancer.\n","abstract":"Rhabdomyosarcoma is a paediatric soft tissue cancer arising from developing muscle. A subset of these tumours harbours a somatic fusion involving the FOXO1 gene, which strongly correlates with poor clinical outcomes and defines a molecularly high-risk group. These fusion-positive cancers are characterized by a gene expression profile resembling mature muscle cells, while fusion-negative tumours typically appear less differentiated.To better understand the cellular origins of lethality in fusion-negative rhabdomyosarcoma, we analysed single-cell transcriptomic profiles and validated our findings using nuclear RNA-sequencing, chromatin accessibility assays, spatial transcriptomics, functional perturbation studies, and external datasets. Our findings highlight a common high-risk cell state that transcends traditional subtype classifications in rhabdomyosarcoma and may inform future therapeutic targeting strategies.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-08-28T10:58:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008272","title":"Molecular subtypes of pancreatic neuroendocrine tumors mutated in MEN1/DAXX/ ATRX explain biological variability","description":"Pancreatic Neuroendocrine Tumors (PanNETs) most probably arise from the islets of Langerhans, although direct evidence is still lacking. About 40% of non-functioning (NF) PanNETs harbour mutations in MEN1, often in conjunction with alterations in DAXX/ATRX. Despite the homogeneous genetic background, the ADM (mutation in DAXX/ATRX and MEN1) group is heterogeneous regarding molecular features and response to treatment. To explore the molecular and clinical heterogeneity within this group, we integrated transcriptomic and DNA methylation data from 36 and 93 samples, respectively. Using a multi-omic approach we described a two-level hierarchy separating PanNET subtypes mutated in MEN1, DAXX and ATRX. \nFirst, DNA methylation discriminates ADM-PanNET from PanNET mutated in MEN1 only (α-like).  Compared to α-like, all ADM tumors exhibit DNA methylation changes at enhancer and lowly methylated regions as well as at peri-centromeric and telomeric regions, associated with alternative lengthening of telomeres, increased chromosomal instability, and enhanced proliferative capacity. At a second level, transcriptomic analysis revealed three distinct ADM subtypes: ADM hypoxic, ADM NST (No Special Type), and ADM immunosuppressive. The ADM hypoxic subtype is characterized by strong hypoxia signature, likely regulated epigenetically. The ADM NST subtype appears to be primarily driven by epigenetic changes that promote proliferation. The ADM immunosuppressive is highly enriched in immune component and strong metastasis-like signature.  While all the three subtypes are highly associated with liver metastasis formation and invasion, the ADM immunosuppressive are significantly smaller (&lt;2.5 cm p.value=0.023) despite displaying aggressive molecular features.\nBy defining these three novel ADM subtypes, our study provides a refined framework for understanding PanNET heterogeneity. This classification underscores potential diagnostic markers and highlights distinct biological vulnerabilities that may inform the development of subtype-tailored therapeutic strategies.\n","abstract":"Pancreatic Neuroendocrine Tumors (PanNETs) most probably arise from the islets of Langerhans, although direct evidence is still lacking. About 40% of non-functioning (NF) PanNETs harbour mutations in MEN1, often in conjunction with alterations in DAXX/ATRX. Despite the homogeneous genetic background, the ADM (mutation in DAXX/ATRX and MEN1) group is heterogeneous regarding molecular features and response to treatment. To explore the molecular and clinical heterogeneity within this group, we integrated transcriptomic and DNA methylation data from 36 and 93 samples, respectively. Using a multi-omic approach we described a two-level hierarchy separating PanNET subtypes mutated in MEN1, DAXX and ATRX. \nFirst, DNA methylation discriminates ADM-PanNET from PanNET mutated in MEN1 only (α-like).  Compared to α-like, all ADM tumors exhibit DNA methylation changes at enhancer and lowly methylated regions as well as at peri-centromeric and telomeric regions, associated with alternative lengthening of telomeres, increased chromosomal instability, and enhanced proliferative capacity. At a second level, transcriptomic analysis revealed three distinct ADM subtypes: ADM hypoxic, ADM NST (No Special Type), and ADM immunosuppressive. The ADM hypoxic subtype is characterized by strong hypoxia signature, likely regulated epigenetically. The ADM NST subtype appears to be primarily driven by epigenetic changes that promote proliferation. The ADM immunosuppressive is highly enriched in immune component and strong metastasis-like signature.  While all the three subtypes are highly associated with liver metastasis formation and invasion, the ADM immunosuppressive are significantly smaller (&lt;2.5 cm p.value=0.023) despite displaying aggressive molecular features.\nBy defining these three novel ADM subtypes, our study provides a refined framework for understanding PanNET heterogeneity. This classification underscores potential diagnostic markers and highlights distinct biological vulnerabilities that may inform the development of subtype-tailored therapeutic strategies.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-08-29T15:08:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008273","title":"Single_cell_RNA_sequencing_of_rhabdomyosarcoma_tumouroids","description":"The aim of this study is to investigate the genomic landscape of human cancer.\n","abstract":"Rhabdomyosarcoma is a paediatric soft tissue cancer arising from developing muscle. A subset of these tumours harbours a somatic fusion involving the FOXO1 gene, which strongly correlates with poor clinical outcomes and defines a molecularly high-risk group. These fusion-positive cancers are characterized by a gene expression profile resembling mature muscle cells, while fusion-negative tumours typically appear less differentiated.To better understand the cellular origins of lethality in fusion-negative rhabdomyosarcoma, we analysed single-cell transcriptomic profiles and validated our findings using nuclear RNA-sequencing, chromatin accessibility assays, spatial transcriptomics, functional perturbation studies, and external datasets. Our findings highlight a common high-risk cell state that transcends traditional subtype classifications in rhabdomyosarcoma and may inform future therapeutic targeting strategies.\n","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-01T14:48:45+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008274","title":"Whole_Genome_sequencing_of_rhabdomyosarcoma_tumour_tissue","description":"The aim of this study is to investigate the genomic landscape of human cancer.\n","abstract":"Rhabdomyosarcoma is a paediatric soft tissue cancer arising from developing muscle. A subset of these tumours harbours a somatic fusion involving the FOXO1 gene, which strongly correlates with poor clinical outcomes and defines a molecularly high-risk group. These fusion-positive cancers are characterized by a gene expression profile resembling mature muscle cells, while fusion-negative tumours typically appear less differentiated.To better understand the cellular origins of lethality in fusion-negative rhabdomyosarcoma, we analysed single-cell transcriptomic profiles and validated our findings using nuclear RNA-sequencing, chromatin accessibility assays, spatial transcriptomics, functional perturbation studies, and external datasets. Our findings highlight a common high-risk cell state that transcends traditional subtype classifications in rhabdomyosarcoma and may inform future therapeutic targeting strategies.\n","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-01T14:49:09+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008275","title":"Single_cell_RNA_sequencing_of_rhabdomyosarcoma_tumour_tissue","description":"The aim of this study is to investigate the genomic landscape of human cancer.\n","abstract":"Rhabdomyosarcoma is a paediatric soft tissue cancer arising from developing muscle. A subset of these tumours harbours a somatic fusion involving the FOXO1 gene, which strongly correlates with poor clinical outcomes and defines a molecularly high-risk group. These fusion-positive cancers are characterized by a gene expression profile resembling mature muscle cells, while fusion-negative tumours typically appear less differentiated.To better understand the cellular origins of lethality in fusion-negative rhabdomyosarcoma, we analysed single-cell transcriptomic profiles and validated our findings using nuclear RNA-sequencing, chromatin accessibility assays, spatial transcriptomics, functional perturbation studies, and external datasets. Our findings highlight a common high-risk cell state that transcends traditional subtype classifications in rhabdomyosarcoma and may inform future therapeutic targeting strategies.\n","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-01T14:49:31+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008276","title":"Single_cell_ATAC_sequencing_of_rhabdomyosarcoma_tumour_tissue","description":"The aim of this study is to investigate the genomic landscape of human cancer.\n","abstract":"Rhabdomyosarcoma is a paediatric soft tissue cancer arising from developing muscle. A subset of these tumours harbours a somatic fusion involving the FOXO1 gene, which strongly correlates with poor clinical outcomes and defines a molecularly high-risk group. These fusion-positive cancers are characterized by a gene expression profile resembling mature muscle cells, while fusion-negative tumours typically appear less differentiated.To better understand the cellular origins of lethality in fusion-negative rhabdomyosarcoma, we analysed single-cell transcriptomic profiles and validated our findings using nuclear RNA-sequencing, chromatin accessibility assays, spatial transcriptomics, functional perturbation studies, and external datasets. Our findings highlight a common high-risk cell state that transcends traditional subtype classifications in rhabdomyosarcoma and may inform future therapeutic targeting strategies.\n","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-01T14:49:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008277","title":"Whole_Genome_sequencing_of_rhabdomyosarcoma_tumour_tissue","description":"The aim of this study is to investigate the genomic landscape of human cancer.\n","abstract":"Rhabdomyosarcoma is a paediatric soft tissue cancer arising from developing muscle. A subset of these tumours harbours a somatic fusion involving the FOXO1 gene, which strongly correlates with poor clinical outcomes and defines a molecularly high-risk group. These fusion-positive cancers are characterized by a gene expression profile resembling mature muscle cells, while fusion-negative tumours typically appear less differentiated.To better understand the cellular origins of lethality in fusion-negative rhabdomyosarcoma, we analysed single-cell transcriptomic profiles and validated our findings using nuclear RNA-sequencing, chromatin accessibility assays, spatial transcriptomics, functional perturbation studies, and external datasets. Our findings highlight a common high-risk cell state that transcends traditional subtype classifications in rhabdomyosarcoma and may inform future therapeutic targeting strategies.\n","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-01T14:49:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008278","title":"Bulk_RNA_sequencing_of_rhabdomyosarcoma_tumour_tissue","description":"The aim of this study is to investigate the genomic landscape of human cancer.\n","abstract":"Rhabdomyosarcoma is a paediatric soft tissue cancer arising from developing muscle. A subset of these tumours harbours a somatic fusion involving the FOXO1 gene, which strongly correlates with poor clinical outcomes and defines a molecularly high-risk group. These fusion-positive cancers are characterized by a gene expression profile resembling mature muscle cells, while fusion-negative tumours typically appear less differentiated.To better understand the cellular origins of lethality in fusion-negative rhabdomyosarcoma, we analysed single-cell transcriptomic profiles and validated our findings using nuclear RNA-sequencing, chromatin accessibility assays, spatial transcriptomics, functional perturbation studies, and external datasets. Our findings highlight a common high-risk cell state that transcends traditional subtype classifications in rhabdomyosarcoma and may inform future therapeutic targeting strategies.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-01T14:50:10+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008279","title":"Single_cell_ATAC_sequencing_of_rhabdomyosarcoma_tumour_tissue","description":"The aim of this study is to investigate the genomic landscape of human cancer.\n","abstract":"Rhabdomyosarcoma is a paediatric soft tissue cancer arising from developing muscle. A subset of these tumours harbours a somatic fusion involving the FOXO1 gene, which strongly correlates with poor clinical outcomes and defines a molecularly high-risk group. These fusion-positive cancers are characterized by a gene expression profile resembling mature muscle cells, while fusion-negative tumours typically appear less differentiated.To better understand the cellular origins of lethality in fusion-negative rhabdomyosarcoma, we analysed single-cell transcriptomic profiles and validated our findings using nuclear RNA-sequencing, chromatin accessibility assays, spatial transcriptomics, functional perturbation studies, and external datasets. Our findings highlight a common high-risk cell state that transcends traditional subtype classifications in rhabdomyosarcoma and may inform future therapeutic targeting strategies.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-01T14:50:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008280","title":"Whole_Genome_sequencing_of_rhabdomyosarcoma_tumour_tissue","description":"The aim of this study is to investigate the genomic landscape of human cancer.\n","abstract":"Rhabdomyosarcoma is a paediatric soft tissue cancer arising from developing muscle. A subset of these tumours harbours a somatic fusion involving the FOXO1 gene, which strongly correlates with poor clinical outcomes and defines a molecularly high-risk group. These fusion-positive cancers are characterized by a gene expression profile resembling mature muscle cells, while fusion-negative tumours typically appear less differentiated.To better understand the cellular origins of lethality in fusion-negative rhabdomyosarcoma, we analysed single-cell transcriptomic profiles and validated our findings using nuclear RNA-sequencing, chromatin accessibility assays, spatial transcriptomics, functional perturbation studies, and external datasets. Our findings highlight a common high-risk cell state that transcends traditional subtype classifications in rhabdomyosarcoma and may inform future therapeutic targeting strategies.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-01T14:50:36+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008281","title":"Single_cell_RNA_sequencing_of_rhabdomyosarcoma_tumour_tissue","description":"The aim of this study is to investigate the genomic landscape of human cancer.\n","abstract":"Rhabdomyosarcoma is a paediatric soft tissue cancer arising from developing muscle. A subset of these tumours harbours a somatic fusion involving the FOXO1 gene, which strongly correlates with poor clinical outcomes and defines a molecularly high-risk group. These fusion-positive cancers are characterized by a gene expression profile resembling mature muscle cells, while fusion-negative tumours typically appear less differentiated.To better understand the cellular origins of lethality in fusion-negative rhabdomyosarcoma, we analysed single-cell transcriptomic profiles and validated our findings using nuclear RNA-sequencing, chromatin accessibility assays, spatial transcriptomics, functional perturbation studies, and external datasets. Our findings highlight a common high-risk cell state that transcends traditional subtype classifications in rhabdomyosarcoma and may inform future therapeutic targeting strategies.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-01T14:51:03+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008282","title":"Bulk_RNA_sequencing_of_rhabdomyosarcoma_tumour_tissue","description":"The aim of this study is to investigate the genomic landscape of human cancer.\n","abstract":"Rhabdomyosarcoma is a paediatric soft tissue cancer arising from developing muscle. A subset of these tumours harbours a somatic fusion involving the FOXO1 gene, which strongly correlates with poor clinical outcomes and defines a molecularly high-risk group. These fusion-positive cancers are characterized by a gene expression profile resembling mature muscle cells, while fusion-negative tumours typically appear less differentiated.To better understand the cellular origins of lethality in fusion-negative rhabdomyosarcoma, we analysed single-cell transcriptomic profiles and validated our findings using nuclear RNA-sequencing, chromatin accessibility assays, spatial transcriptomics, functional perturbation studies, and external datasets. Our findings highlight a common high-risk cell state that transcends traditional subtype classifications in rhabdomyosarcoma and may inform future therapeutic targeting strategies.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-01T14:51:15+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008283","title":"Single_cell_ATAC_sequencing_of_rhabdomyosarcoma_tumour_tissue","description":"The aim of this study is to investigate the genomic landscape of human cancer.\n","abstract":"Rhabdomyosarcoma is a paediatric soft tissue cancer arising from developing muscle. A subset of these tumours harbours a somatic fusion involving the FOXO1 gene, which strongly correlates with poor clinical outcomes and defines a molecularly high-risk group. These fusion-positive cancers are characterized by a gene expression profile resembling mature muscle cells, while fusion-negative tumours typically appear less differentiated.To better understand the cellular origins of lethality in fusion-negative rhabdomyosarcoma, we analysed single-cell transcriptomic profiles and validated our findings using nuclear RNA-sequencing, chromatin accessibility assays, spatial transcriptomics, functional perturbation studies, and external datasets. Our findings highlight a common high-risk cell state that transcends traditional subtype classifications in rhabdomyosarcoma and may inform future therapeutic targeting strategies.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-01T14:51:27+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008284","title":"Human_UV_Skin_PFPE_Sections___RNA","description":"This study will involve sectioning PAXgene-fixed paraffin embedded (PFPE) blocks of human skin, taken from patients before and after a narrow-band UV-B exposure regime. Following sectioning, non-epidermal tissues will be removed and RNA extracted from the epidermis for low-input sequencing. This will reveal the transcriptional changes that are induced by UV, considering factors such as skin pigmentation, UV dose and time since last UV exposure.","abstract":"Within the epidermis, UV irradiation has numerous roles in shaping the somatic mutational landscape. These include induction of DNA damage and promotion of clonal expansion, thus acting as a tumour initiator and tumour promoter. The response to UV varies greatly across individuals, with factors such as skin pigmentation contributing to this variability. This study will involve sectioning PFPE blocks of human skin, taken from patients before and after exposure to NB-UVB. Following RNA extraction, the transcriptional changes induced by NB-UVB will be revealed, and the variation across genotypes will be investigated.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008285","title":"Noorani_UGI_Inherited_Targeted_Nanoseq","description":"Oesophageal cancer is the 6th most common cause of cancer death worldwide with an overall 5 year survival of 10-25%. State of the art sequencing technologies have demonstrated that canonical driver mutations occur in normal tissues across organ types, challenging traditional understanding of clonal evolution in cancer development and presenting the opportunity to detect hidden genomic alterations in tissues with an increased cancer risk. This study aims to comprehensively identify the genomic alterations in benign oesophageal diseases with an increased cancer risk, including Chagas mega-oesophagus in 200 cases. Through combined duplex sequencing and Laser Capture Microdissection we aim to reconstruct the landscape of these diseases in unprecedented deail.","abstract":"Inherited Cancer Risk in UGI - Targeted-Nanoseq Samples","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008286","title":"Tumor-agnostic plasma approach for pleural mesothelioma","description":"Pleural Mesothelioma is an aggressive tumor with poor prognosis. Tumor monitoring is difficult since tumor biopsies are often inaccessible and standard imaging approaches lack sensitivity.\nWe propose a tumor-agnostic liquid-biopsy approach called Janus-seq to monitor tumor dynamics using a multiple layers, such as fragmentomics, tumor fraction, and somatic copy number alterations. Further, a targeted approach was applied to the same library preparation to sequence 178 cancer-related genes to detect somatic nucleotide variants.","abstract":"Pleural Mesothelioma is an aggressive tumor with poor prognosis. Tumor monitoring is difficult since tumor biopsies are often inaccessible and standard imaging approaches lack sensitivity.\nWe propose a tumor-agnostic liquid-biopsy approach called Janus-seq to monitor tumor dynamics using a multiple layers, such as fragmentomics, tumor fraction, and somatic copy number alterations. Further, a targeted approach was applied to the same library preparation to sequence 178 cancer-related genes to detect somatic nucleotide variants.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008287","title":"DERMATLAS__Cutaneous_angiosarcoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are cutaneous angiosarcomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are cutaneous angiosarcomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008288","title":"DERMATLAS__Cutaneous_angiosarcoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are cutaneous angiosarcomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are cutaneous angiosarcomas.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008289","title":"Targeted_NanoSeq_of_Paediatric_IBD_Lymphocytes","description":"Targeted NanoSeq of Paediatric IBD Lymphocytes","abstract":"Targeted NanoSeq of Paediatric IBD Lymphocytes","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008290","title":"CLD_targeted_nanoseq","description":"Targeted nanoseq of chronic liver disease using bespoke Twist targeted liver panel.","abstract":"Part of the development of the chronic liver disease somatic mutational atlas - studying the adaptive mutational pathways developed by hepatocytes on their path towards end-stage liver disease.  ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008291","title":"WGS_long_read__human_panbody_tissues","description":"Bulk long-read sequencing to support resoving haplotype and phasing short-read data.","abstract":"Bulk long-read sequencing to support resoving haplotype and phasing short-read data.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008292","title":"Targeted_NanoSeq___Investigating_the_Role_of_Somatic_Mutations_in_Inflammatory_Liver_Disease","description":"This is an exploratory study aimed at investigating the mutational landscape in inflammatory liver diseases and assessing its relevance to the initiation and progression of these diseases.\n\nWe aim to \n1.\tIdentify genetic alterations in inflammatory liver diseases.\n2.\tDetermine which cell populations harbour with genetic alterations.\n3.\tCharacterise the functional role of the genetic alterations.\n","abstract":"Inflammatory liver diseases are mediated by acute or chronic tissue inflammation in the liver which can lead to fibrosis and cirrhosis. There can be several causes of liver inflammation including autoimmunity, chemical exposure and viruses. Autoimmune liver disease such as autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are debilitating conditions where the immune system attacks different parts of the liver. The cause of these conditions is unknown, and most treatments are ineffective with liver transplantation often being required as the disease progresses.\n\nGenetic and environmental factors contribute to the variability in the disease course and response to treatment among different individuals. It is not clear if the mutations found in the different tissues of the liver can play a part in the development and progression of these diseases. \n\nThis study aims to use novel methods to identify mutations that drive progression or protect the cells from inflammatory damage to identify in the different types of tissues of individuals with inflammatory liver diseases.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008293","title":"Immunodeficiency syndrome caused by LCP1 mutations","description":"Severe congenital neutropenia (SCN) is characterized by neutropenia, recurrent infections and an increased leukemia risk. Multiple genetic defects underlying SCN have been identified, but a genetic diagnosis is still lacking in a significant proportion of patients. Here, we report three independent pedigrees with autosomal dominant variants in LCP1. Variants c.740-1G&gt;T and c.740-20_744del resulted in the same alternatively spliced RNA product, causing an in-frame deletion (p.A247_E254del). Variant c.509C&gt;T in the third pedigree resulted in p.S170L. Variant carriers suffer from neutropenia, poor or complete lack of response to G-CSF treatment, and variable degrees of lymphopenia. Patients with A247_E254del presented with tetraploid cells in the bone marrow, indicative of disturbed cytokinesis. In one of these kindreds, two individuals developed acute leukemia. G-CSF non-responsiveness and defective cell cycling were repaired upon correction of the LCP1 A247_E254del variant in patient-derived induced pluripotent stem cells, supporting the monogenic origin of the disease. Indicative of their gain-of-function, both A247_E254del and S170L variants increased F-actin bundling and formation of abnormal protrusions. Single-cell transcriptome analysis of A247_E254del bone marrow-derived hematopoietic stem and progenitor cells (HSPCs) showed deregulation of signaling pathways controlling mitosis in multi-lineage and lymphoid-primed HSPC subsets. We conclude that activating LCP1 variants cause a new autosomal dominant hematopoietic disorder. Depending on the consequences of the LCP1 variants for protein structure, patients may suffer from G-CSF refractory severe neutropenia, lymphopenia, defective cytokinesis and predisposition to leukemia. ","abstract":"Severe congenital neutropenia (SCN) is characterized by neutropenia, recurrent infections and an increased leukemia risk. Multiple genetic defects underlying SCN have been identified, but a genetic diagnosis is still lacking in a significant proportion of patients. Here, we report three independent pedigrees with autosomal dominant variants in LCP1. Variants c.740-1G&gt;T and c.740-20_744del resulted in the same alternatively spliced RNA product, causing an in-frame deletion (p.A247_E254del). Variant c.509C&gt;T in the third pedigree resulted in p.S170L. Variant carriers suffer from neutropenia, poor or complete lack of response to G-CSF treatment, and variable degrees of lymphopenia. Patients with A247_E254del presented with tetraploid cells in the bone marrow, indicative of disturbed cytokinesis. In one of these kindreds, two individuals developed acute leukemia. G-CSF non-responsiveness and defective cell cycling were repaired upon correction of the LCP1 A247_E254del variant in patient-derived induced pluripotent stem cells, supporting the monogenic origin of the disease. Indicative of their gain-of-function, both A247_E254del and S170L variants increased F-actin bundling and formation of abnormal protrusions. Single-cell transcriptome analysis of A247_E254del bone marrow-derived hematopoietic stem and progenitor cells (HSPCs) showed deregulation of signaling pathways controlling mitosis in multi-lineage and lymphoid-primed HSPC subsets. We conclude that activating LCP1 variants cause a new autosomal dominant hematopoietic disorder. Depending on the consequences of the LCP1 variants for protein structure, patients may suffer from G-CSF refractory severe neutropenia, lymphopenia, defective cytokinesis and predisposition to leukemia. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-03T17:02:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008294","title":"Delivering precision oncology in metastatic breast cancer: Clinical impact of comprehensive genomic profiling within the CATCH platform","description":"Metastatic breast cancer (mBC) remains a significant clinical challenge,\ndespite advances in treatment. This study reports the results of the CATCH platform, a comprehensive genomic and transcriptomic profiling initiative for patients with mBC, aiming to identify actionable alterations and guide treatment decisions.  412 patients with mBC undergoing profiling were analyzed, revealing actionable mutations in *PIK3CA*, *AKT1*, *ESR1*, and *BRCA1/2* being the most frequent.  Molecularly-guided treatment was implemented in 44.4% of patients, demonstrating a disease control rate of 58.6% and an objective response rate of 27.0%. Patients benefiting from the MTB-guided treatment showed a significantly prolonged progression-free survival (PFS) ratio (PFS2/PFS1 ≥1.5) in one third of cases. Notably, 16.7% of patients harbored mutations in inherited cancer predisposition genes, highlighting the potential for genetic counseling. The CATCH platform demonstrates the feasibility and benefit of comprehensive molecular profiling in mBC, offering a pathway towards personalized treatment strategies and improved patient outcomes. Further expansion of this platform and integration with clinical trials are warranted to fully assess long-term benefits and address challenges in translating precision oncology into routine clinical practice.","abstract":"Metastatic breast cancer (mBC) remains a significant clinical challenge,\ndespite advances in treatment. This study reports the results of the CATCH platform, a comprehensive genomic and transcriptomic profiling initiative for patients with mBC, aiming to identify actionable alterations and guide treatment decisions.  412 patients with mBC undergoing profiling were analyzed, revealing actionable mutations in *PIK3CA*, *AKT1*, *ESR1*, and *BRCA1/2* being the most frequent.  Molecularly-guided treatment was implemented in 44.4% of patients, demonstrating a disease control rate of 58.6% and an objective response rate of 27.0%. Patients benefiting from the MTB-guided treatment showed a significantly prolonged progression-free survival (PFS) ratio (PFS2/PFS1 ≥1.5) in one third of cases. Notably, 16.7% of patients harbored mutations in inherited cancer predisposition genes, highlighting the potential for genetic counseling. The CATCH platform demonstrates the feasibility and benefit of comprehensive molecular profiling in mBC, offering a pathway towards personalized treatment strategies and improved patient outcomes. Further expansion of this platform and integration with clinical trials are warranted to fully assess long-term benefits and address challenges in translating precision oncology into routine clinical practice.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008295","title":"CUT&RUN-sequencing identifies PTK7 as a direct Wnt target in patient-derived colorectal cancer organoids","description":"The aberrant activation of Wnt/β-catenin signaling by APC mutations is a hallmark of colorectal cancer (CRC), but targeting Wnt signaling therapeutically has proven challenging. Deciphering the molecular effects of mutant APC-driven Wnt activation is crucial to enable the discovery of novel therapeutic targets. Here, we employ CUT&amp;RUN-sequencing in patient-derived CRC organoids derived from two donors to dissect the transcriptional regulation by β-catenin in CRC. This analysis identified several genes of interest for CRC development as potential β-catenin target genes. Among these, we characterize PTK7, a co-receptor of the Wnt pathway and stem cell marker, as a main transcriptional target of β-catenin in CRC. We confirm that the expression of PTK7 is directly regulated by β-catenin in a comprehensive panel of CRC models. We demonstrate that APC mutations introduced by CRISPR/Cas9 result in the upregulation of PTK7 expression in human colon organoids, underlining the relevance of this upregulation during CRC carcinogenesis. Finally, we show that PTK7 promotes proliferation in CRC models without definitively affecting canonical Wnt signaling. Together, these results suggest that PTK7, which can be potentially targeted by existing drugs, is a Wnt target gene that contributes to oncogenic growth in CRC.","abstract":"The aberrant activation of Wnt/β-catenin signaling by APC mutations is a hallmark of colorectal cancer (CRC), but targeting Wnt signaling therapeutically has proven challenging. Deciphering the molecular effects of mutant APC-driven Wnt activation is crucial to enable the discovery of novel therapeutic targets. Here, we employ CUT&amp;RUN-sequencing in patient-derived CRC organoids derived from two donors to dissect the transcriptional regulation by β-catenin in CRC. This analysis identified several genes of interest for CRC development as potential β-catenin target genes. Among these, we characterize PTK7, a co-receptor of the Wnt pathway and stem cell marker, as a main transcriptional target of β-catenin in CRC. We confirm that the expression of PTK7 is directly regulated by β-catenin in a comprehensive panel of CRC models. We demonstrate that APC mutations introduced by CRISPR/Cas9 result in the upregulation of PTK7 expression in human colon organoids, underlining the relevance of this upregulation during CRC carcinogenesis. Finally, we show that PTK7 promotes proliferation in CRC models without definitively affecting canonical Wnt signaling. Together, these results suggest that PTK7, which can be potentially targeted by existing drugs, is a Wnt target gene that contributes to oncogenic growth in CRC.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-04T10:58:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008296","title":"Common genetic determinants of dynamic human in vivo immune response to Mycobacterium tuberculosis. ","description":"This cohort includes individuals with Tuberculosis (TB) enrolled in the Human Immune Response Variation (HIRV) study. TB remains a significant global health challenge.  Although many people are infected with the bacteria that cause TB, only some go on to develop the disease, and the reasons for this remain unclear. The aim of this study is to investigate whether individual susceptibility to TB is mediated by genetic variation in immune response to infection. DNA was extracted from cryopreserved whole blood samples from 267 participants using the QIAamp spin column kit. Genotyping was done with the Illumina Infinium Global Diversity Array, and data were imputed using the Michigan Imputation Server with the Haplotype Reference Consortium panel r1.1 as the reference.","abstract":"This cohort includes individuals with Tuberculosis (TB) enrolled in the Human Immune Response Variation (HIRV) study. TB remains a significant global health challenge.  Although many people are infected with the bacteria that cause TB, only some go on to develop the disease, and the reasons for this remain unclear. The aim of this study is to investigate whether individual susceptibility to TB is mediated by genetic variation in immune response to infection. DNA was extracted from cryopreserved whole blood samples from 267 participants using the QIAamp spin column kit. Genotyping was done with the Illumina Infinium Global Diversity Array, and data were imputed using the Michigan Imputation Server with the Haplotype Reference Consortium panel r1.1 as the reference.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008297","title":"Validation of a Genome-Wide Polygenic Score for Body Mass Index in South Asians","description":"Genotyping data of BMI model markers generated using Global Screening Array (Illumina Inc.)\n","abstract":"Genotyping data of BMI model markers generated using Global Screening Array (Illumina Inc.)\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008298","title":"Duplex sequencing in NF2-related schwannomatosis","description":"Background: Schwannomatosis (SWN) is a rare tumor predisposition syndrome caused by pathogenic variants in NF2, SMARCB1, or LZTR1. Mosaicism contributes to up to 30% of de novo NF2-related cases, but its role in  SMARCB1- and LZTR1-related SWN remains unclear. Accurate molecular classification is critical for clinical management, yet overlapping phenotypes complicate diagnosis. Because standard diagnostics have limited sensitivity and often require tumor tissue, we evaluated whether ultra-sensitive duplex sequencing of blood-derived DNA improves mosaic variant detection in SWN.\nMethods: We developed a duplex sequencing assay targeting NF2, SMARCB1, and LZTR1 and analyzed 102 individuals with suspected SWN previously negative for constitutional pathogenic variants, along with 35 controls. \nResults: Duplex sequencing identified low-level mosaic NF2 pathogenic variants in 11% of cases (11/102), with variant allele frequencies as low as 0.06%. In all patients with available tumor material (8/11), blood and tumor findings were concordant. No mosaic pathogenic variants were detected in SMARCB1 or LZTR1. Controls showed no deleterious variants except one LZTR1 splice-site variant. \nConclusions: Duplex sequencing enables robust detection of ultra-low-frequency NF2 variants in SWN and complements existing diagnostic workflows. This approach may reduce dependence on tumor tissue in NF2-related SWN, improve differential diagnosis, and support patient management and genetic counseling. \n","abstract":"Background: Schwannomatosis (SWN) is a rare tumor predisposition syndrome caused by pathogenic variants in NF2, SMARCB1, or LZTR1. Mosaicism contributes to up to 30% of de novo NF2-related cases, but its role in  SMARCB1- and LZTR1-related SWN remains unclear. Accurate molecular classification is critical for clinical management, yet overlapping phenotypes complicate diagnosis. Because standard diagnostics have limited sensitivity and often require tumor tissue, we evaluated whether ultra-sensitive duplex sequencing of blood-derived DNA improves mosaic variant detection in SWN.\nMethods: We developed a duplex sequencing assay targeting NF2, SMARCB1, and LZTR1 and analyzed 102 individuals with suspected SWN previously negative for constitutional pathogenic variants, along with 35 controls. \nResults: Duplex sequencing identified low-level mosaic NF2 pathogenic variants in 11% of cases (11/102), with variant allele frequencies as low as 0.06%. In all patients with available tumor material (8/11), blood and tumor findings were concordant. No mosaic pathogenic variants were detected in SMARCB1 or LZTR1. Controls showed no deleterious variants except one LZTR1 splice-site variant. \nConclusions: Duplex sequencing enables robust detection of ultra-low-frequency NF2 variants in SWN and complements existing diagnostic workflows. This approach may reduce dependence on tumor tissue in NF2-related SWN, improve differential diagnosis, and support patient management and genetic counseling. \n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-07T20:38:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008299","title":"Lung_Cell_Atlas__Paediatric_RNA","description":"Single cell sequencing will be carried out by multiome profiling (RNAseq and ATACseq). Additonal modalities may be examined. Spatial profiling may involve Visium, Curio and other technologies. This data set will feed into a larger analysis of the human lungs over development, that aims to detail all the cell types of the human lungs and airways and will extend current knowledge by providing chromatin accessibility data that will allow us to link GWAS data and identify regulatory networks and then compare these against fetal and adult data sets\n","abstract":"As part of the CZI funded lung seed network, we are profiling paediatric lung samples, at both the single cell and the spatial level.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-08T12:49:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008300","title":"Lung_Cell_Atlas__Paediatric_Spatial","description":"Single cell sequencing will be carried out by multiome profiling (RNAseq and ATACseq). Additonal modalities may be examined. Spatial profiling may involve Visium, Curio and other technologies. This data set will feed into a larger analysis of the human lungs over development, that aims to detail all the cell types of the human lungs and airways and will extend current knowledge by providing chromatin accessibility data that will allow us to link GWAS data and identify regulatory networks and then compare these against fetal and adult data sets\n","abstract":"As part of the CZI funded lung seed network, we are profiling paediatric lung samples, at spatial and the single cell level.\n","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-08T12:57:23+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008302","title":"Diseased_heart_analysis__RNA_Adult","description":"Samples for this project are taken from adult human hearts which have been preserved using 2 different methods (cold static storage on ice, and hypothermic perfusion). Samples have been acquired at various time points during post-preservation normothermic perfusion. The aim of the project is to assess the transcriptional changes caused by these differing methods of preservation.\n","abstract":"Samples for this project are taken from adult human hearts which have been preserved using 2 different methods (cold static storage on ice, and hypothermic perfusion). Samples have been acquired at various time points during post-preservation normothermic perfusion.\n","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-08T14:33:17+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008303","title":"TRON tumor-naïve ctDNA detection ","description":"Circulating tumor DNA (ctDNA) detection offers non-invasive monitoring of cancer from blood samples. While tumor-informed approaches are sensitive, their clinical application is limited by cost, tissue availability, and turnaround time. In contrast, tumor-naïve assays are more rapid and broadly applicable but often sacrifice sensitivity.\nHere, we present DEEPctMUT, a computational pipeline for tumor-naïve ctDNA detection that integrates unique molecular identifiers (UMIs) with three complementary error-polishing strategies: (1) machine learning-based sequencing error suppression, (2) deep learning-based background noise filtering (DeepES), and (3) removal of clonal hematopoietic mutations using matched peripheral blood. We designed an efficient sequencing panel and developed and validated DEEPctMUT using cell lines, spike-in samples, healthy and CRC plasma samples. DEEPctMUT accurately detected mutations down to a 0.03% VAF, outperforming other tumor-naïve methods. In a head-to-head comparison, our pipeline identified pre-surgical CRC cases with 100% accuracy, whereas the Roche Avenio Surveillance Kit achieved only 50% sensitivity. Furthermore, a highly versatile panel-independent model in DEEPctMUT could improve existing Roche Avenio performance without further Avenio specific training. We make the extensive ground truth data and the fully adaptable DEEPctMUT pipeline and models available. \nOur findings underscore that advanced error polishing methods can effectively compensate for the absence of matched tumor information, enabling sensitive ctDNA detection.\n","abstract":"Circulating tumor DNA (ctDNA) detection offers non-invasive monitoring of cancer from blood samples. While tumor-informed approaches are sensitive, their clinical application is limited by cost, tissue availability, and turnaround time. In contrast, tumor-naïve assays are more rapid and broadly applicable but often sacrifice sensitivity.\nHere, we present DEEPctMUT, a computational pipeline for tumor-naïve ctDNA detection that integrates unique molecular identifiers (UMIs) with three complementary error-polishing strategies: (1) machine learning-based sequencing error suppression, (2) deep learning-based background noise filtering (DeepES), and (3) removal of clonal hematopoietic mutations using matched peripheral blood. We designed an efficient sequencing panel and developed and validated DEEPctMUT using cell lines, spike-in samples, healthy and CRC plasma samples. DEEPctMUT accurately detected mutations down to a 0.03% VAF, outperforming other tumor-naïve methods. In a head-to-head comparison, our pipeline identified pre-surgical CRC cases with 100% accuracy, whereas the Roche Avenio Surveillance Kit achieved only 50% sensitivity. Furthermore, a highly versatile panel-independent model in DEEPctMUT could improve existing Roche Avenio performance without further Avenio specific training. We make the extensive ground truth data and the fully adaptable DEEPctMUT pipeline and models available. \nOur findings underscore that advanced error polishing methods can effectively compensate for the absence of matched tumor information, enabling sensitive ctDNA detection.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008304","title":"Extended Follow-up of a Response-Guided Bladder-Sparing Treatment Approach for Muscle-Invasive Bladder Cancer and Monitoring of Plasma and Urine Tumor DNA","description":"Neoadjuvant systemic therapy yields pathological complete responses in some patients with muscle-invasive bladder cancer (MIBC), suggesting select patients may avoid cystectomy. We previously reported the results of the HCRN GU16-257 trial exploring a response-guided approach to MIBC in which patients achieving a clinical complete response (cCR) after gemcitabine, cisplatin, and nivolumab could forgo cystectomy. Here we report long-term follow-up and explore circulating tumor DNA (ctDNA) and urine tumor DNA (utDNA) to refine future patient selection. At 47-months median follow-up, cCR status was prognostic for metastasis-free and overall survival. Three-year bladder-intact survival among cCR patients was 69%. Undetectable baseline ctDNA was associated with exceptionally low metastatic risk. Among non-cCR patients, undetectable ctDNA at restaging (prior to definitive local therapy) was associated with better metastasis-free survival. Detectable utDNA in cCR patients was associated with inferior bladder-intact survival. These findings establish a framework for incorporating ctDNA and utDNA into response-guided bladder-sparing paradigms.","abstract":"Neoadjuvant systemic therapy yields pathological complete responses in some patients with muscle-invasive bladder cancer (MIBC), suggesting select patients may avoid cystectomy. We previously reported the results of the HCRN GU16-257 trial exploring a response-guided approach to MIBC in which patients achieving a clinical complete response (cCR) after gemcitabine, cisplatin, and nivolumab could forgo cystectomy. Here we report long-term follow-up and explore circulating tumor DNA (ctDNA) and urine tumor DNA (utDNA) to refine future patient selection. At 47-months median follow-up, cCR status was prognostic for metastasis-free and overall survival. Three-year bladder-intact survival among cCR patients was 69%. Undetectable baseline ctDNA was associated with exceptionally low metastatic risk. Among non-cCR patients, undetectable ctDNA at restaging (prior to definitive local therapy) was associated with better metastasis-free survival. Detectable utDNA in cCR patients was associated with inferior bladder-intact survival. These findings establish a framework for incorporating ctDNA and utDNA into response-guided bladder-sparing paradigms.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-08T15:03:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008305","title":"Patient-derived pediatric brain tumor organoids faithfully recapitulate primary tumors","description":"Extensive molecular analysis by many groups has revealed a heterogeneous landscape of embryonal brain tumors, including medulloblastoma (MB) and atypical teratoid/rhabdoid tumor (ATRT). MB, the most common malignant pediatric brain tumor, is comprised of four molecularly distinct subgroups: Wingless (WNT), Sonic Hedgehog (SHH), Group 3 (G3), and Group 4 (G4). Among these, MB-SHH harboring MYCN amplification and TP53 mutation and MB-G3 with MYC overexpression or amplification constitute the most aggressive tumors, have the poorest clinical outcomes, and lack effective therapeutic options for recurrent disease. Here we describe the establishment of tumor organoid (TO) models from patient-derived orthotopic xenografts (PDOX) of MYCN-amplified and TP53-mutant MB-SHH, MYC-amplified MB-G3 and two ATRT which all grew in mice when reimplanted into the cortices of naïve recipient animals (TOX). Methylation, bulk and single-cell RNA sequencing, and whole genome sequencing demonstrated that TOs and TOXs faithfully recapitulated the molecular landscape and heterogeneity of PDOXs and primary patient tumors compared to established cell lines. The development of TOs will facilitate in vitro high-throughput drug or CRISPR screens without the need for use tumor-bearing mice. This will also accelerate the identification and validation of new vulnerabilities and in vivo preclinical testing toward clinical trials.","abstract":"Extensive molecular analysis by many groups has revealed a heterogeneous landscape of embryonal brain tumors, including medulloblastoma (MB) and atypical teratoid/rhabdoid tumor (ATRT). MB, the most common malignant pediatric brain tumor, is comprised of four molecularly distinct subgroups: Wingless (WNT), Sonic Hedgehog (SHH), Group 3 (G3), and Group 4 (G4). Among these, MB-SHH harboring MYCN amplification and TP53 mutation and MB-G3 with MYC overexpression or amplification constitute the most aggressive tumors, have the poorest clinical outcomes, and lack effective therapeutic options for recurrent disease. Here we describe the establishment of tumor organoid (TO) models from patient-derived orthotopic xenografts (PDOX) of MYCN-amplified and TP53-mutant MB-SHH, MYC-amplified MB-G3 and two ATRT which all grew in mice when reimplanted into the cortices of naïve recipient animals (TOX). Methylation, bulk and single-cell RNA sequencing, and whole genome sequencing demonstrated that TOs and TOXs faithfully recapitulated the molecular landscape and heterogeneity of PDOXs and primary patient tumors compared to established cell lines. The development of TOs will facilitate in vitro high-throughput drug or CRISPR screens without the need for use tumor-bearing mice. This will also accelerate the identification and validation of new vulnerabilities and in vivo preclinical testing toward clinical trials.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-09T17:37:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008306","title":"Toward PRecisiOn Medicine for the Prediction of Treatment Response in Major Depressive Disorder through Stratification of Combined Clinical and Omics Signatures","description":"Major depressive disorder (MDD) is the most common psychiatric disorder worldwide. Pharmacotherapy is the standard first-line treatment, yet only one third of patients respond to the initial trial and about 30% develop treatment-resistant depression (TRD), which is associated with specific clinical and molecular features.\n\nThe PROMPT project aims to develop a precision medicine algorithm for early identification of non-responders. The study is organized in two phases: Phase 1 includes a retrospective cohort of 300 MDD patients (150 TRD and 150 responders) and Phase 2 follows a naturalistic cohort of MDD patients to validate the predictive performance of the algorithm under real-world conditions. Both phases include deep clinical and molecular profiling (genomic, transcriptomic and miRNomic data from both phases) of MDD patients.\n\nFurther information is available at the project website https://www.prompt-depression.org/\n and at the Zenodo community repository https://zenodo.org/communities/prompt_depression\n.","abstract":"Major depressive disorder (MDD) is the most common psychiatric disorder worldwide. Pharmacotherapy is the standard first-line treatment, yet only one third of patients respond to the initial trial and about 30% develop treatment-resistant depression (TRD), which is associated with specific clinical and molecular features.\n\nThe PROMPT project aims to develop a precision medicine algorithm for early identification of non-responders. The study is organized in two phases: Phase 1 includes a retrospective cohort of 300 MDD patients (150 TRD and 150 responders) and Phase 2 follows a naturalistic cohort of MDD patients to validate the predictive performance of the algorithm under real-world conditions. Both phases include deep clinical and molecular profiling (genomic, transcriptomic and miRNomic data from both phases) of MDD patients.\n\nFurther information is available at the project website https://www.prompt-depression.org/\n and at the Zenodo community repository https://zenodo.org/communities/prompt_depression\n.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008307","title":"OPEN_IBD_single_cell_Transcriptomics","description":"Open-IBD will deliver a step-change in our ability to build robust therapeutic hypotheses and identify biomarkers for inflammatory bowel disease (IBD; encompassing Crohn’s disease (CD) and ulcerative colitis (UC)) susceptibility and progression. We will collect whole blood and stool samples at diagnosis, month 3, 6, 9, 12, 18 and 24, alongside gut biopsies at diagnosis and month 12 at colonoscopy or flexible sigmoidoscopy. \n\nWe will generate single cell Transcriptomics data from PBMCs isolated from blood collected at baseline and month 12 after. We will generate 5’ single-cell RNAseq data through the Sanger Institute’s high-throughput single-cell 10x pipeline. 10 samples will be multiplexed per 10X reaction, with an average output of 5000 single cells per donor aiming for a sequencing coverage of 50K reads/cell","abstract":"Open-IBD, a longitudinal multi-omics inception cohort in IBD to address this unmet need. Studying the biology of IBD from the point of diagnosis, without the confounders of time, uncontrolled inflammation and exposure to multiple therapies, provides an unparalleled opportunity for deriving biomarkers and mechanistic insights that aid the discovery and validation of therapeutic targets in IBD.\n\n1,000 IBD research participants will be recruited from diagnostic referral pathways between primary and secondary care from seven NHS sites by co-applicants across the United Kingdom. \n\nOpen-IBD focuses on deriving blood and tissue single-cell transcriptome, alongside gut and stool microbiome and virome data. \n\nOpen-IBD will deliver a step-change in our ability to build robust therapeutic hypotheses and identify biomarkers for inflammatory bowel disease (IBD; encompassing Crohn’s disease (CD) and ulcerative colitis (UC)) susceptibility and progression. We will collect whole blood and stool samples at diagnosis, month 3, 6, 9, 12, 18 and 24, alongside gut biopsies at diagnosis and month 12 at colonoscopy or flexible sigmoidoscopy. \n\nBy collecting outcome and disease progression data of these patients for up to four years we will:\nProvide a deep multi-omic characterisation of early-stage IBD (approximately 1:1 CD:UC) in a large cohort of 1,000 newly diagnosed patients.\nIdentify molecular, cellular, bacterial and viral biomarkers of long-term outcomes in IBD, including disease progression and drug response.\nNominate causal factors driving IBD pathology, including in individuals with progressive disease that is difficult to manage using existing therapies.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008309","title":"Validation of a genome-wide polygenic score for body mass index in South Asians","description":"Genotyping data of BMI model markers generated using Global Screening Array (Illumina Inc.)\n","abstract":"Obesity is a complex disorder, manifested by the interaction of inherited and environmental factors and modulated by a person’s lifestyle habits. India has witnessed more than a two-fold increase in the number of overweight adults in the last 30 years. The polygenic risk score (PRS) quantitatively measures an individual’s risk for common diseases. The PRS for obesity have been validated in the Caucasian population but not in the South Asian (SAS) population. In this study, we benchmarked and validated the existing genome-wide PRS model of obesity with 2.1 million variants in the SAS population. We analyzed a total of 14,263 individuals from three different South Asian cohorts. We compared the risk score with the body mass index (BMI) categories (underweight, normal weight, overweight, and obese) in all three cohorts. High PRS was associated with increased BMI in all the three cohorts. This study also compared validation results from another population-specific PRS model for the BMI. We conclude that high PRS is associated with high BMI in South Asians. Our study suggests that the PRS score can perhaps be an early predictor of overweight and obesity in the South Asian population.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-13T17:49:55+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008310","title":"Pan-cancer MSI and Lynch syndrome ","description":"The study aimed to systematically study MSI/ MMRd status in tumour DNA and germline mutations in mismatch repair (MMR) genes across a unique, large and heterogeneous group of commonly observed non-colorectal  gastrointestinal and genitourinary tumours in the Indian population.  \n","abstract":"The study aimed to systematically study MSI/ MMRd status in tumour DNA and germline mutations in mismatch repair (MMR) genes across a unique, large and heterogeneous group of commonly observed non-colorectal  gastrointestinal and genitourinary tumours in the Indian population.  \n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008311","title":"DERMATLAS__Basaloid_tumour_case_study_WGS","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are a familial basaloid tumour.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are a familial basaloid tumour.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008312","title":"DERMATLAS__Basaloid_tumour_case_study_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are a familial basaloid tumour.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are a familial basaloid tumour.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008313","title":"DERMATLAS__Basaloid_tumour_case_study_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are a familial basaloid tumour.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are a familial basaloid tumour.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008314","title":"Pleuritis_lymphocyte_LCM_Targeted_NanoSeq","description":"Targeted NanoSeq in pleura of donors with evidence of pleuritis with and without exposure to asbestos.","abstract":"Investigation of the mutational landscape of pleura with evidence of lymphocyte infiltration.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008315","title":"Epigenetic profiling of acute myeloid leukemia","description":"To investigate the epigenetic heterogeneity of acute myeloid leukemia (AML), we analyzed a cohort of AML patients using ATAC-seq (n=1563), targeted-capture sequencing (n=1563), and RNA-seq (n=1398). Subsets of cases were also analyzed using EPIC DNA methylation array (n=424), ChIP-seq (for H3K27ac (n=234), H3K27me3 (n=217), SMC1 (n=209), CTCF (n=218), and RPB1 (n=220)), and single-cell RNA- and ATAC-seq (n=36). ","abstract":"To investigate the epigenetic heterogeneity of acute myeloid leukemia (AML), we analyzed a cohort of AML patients using ATAC-seq (n=1563), targeted-capture sequencing (n=1563), and RNA-seq (n=1398). Subsets of cases were also analyzed using EPIC DNA methylation array (n=424), ChIP-seq (for H3K27ac (n=234), H3K27me3 (n=217), SMC1 (n=209), CTCF (n=218), and RPB1 (n=220)), and single-cell RNA- and ATAC-seq (n=36). ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-19T06:15:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008316","title":"GWAS of SJS/TEN in Thai population","description":"This study looks at the Phenytoin-Induced SJS/TEN development based on SNP genotyping data of 1965 individuals from Thailand. Their normal DNAs were genotyped on Illumina HumanOmniExpressExome-8 v1.2 array.","abstract":"This study looks at the Phenytoin-Induced SJS/TEN development based on SNP genotyping data of 1965 individuals from Thailand. Their normal DNAs were genotyped on Illumina HumanOmniExpressExome-8 v1.2 array.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-21T19:14:54+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008317","title":"Bulk_RNA_sequencing_of_rhabdomyosarcoma_tumour_tissue","description":"The aim of this study is to investigate the genomic landscape of human cancer.\n","abstract":"Rhabdomyosarcoma is a paediatric soft tissue cancer arising from developing muscle. A subset of these tumours harbours a somatic fusion involving the FOXO1 gene, which strongly correlates with poor clinical outcomes and defines a molecularly high-risk group. These fusion-positive cancers are characterized by a gene expression profile resembling mature muscle cells, while fusion-negative tumours typically appear less differentiated.To better understand the cellular origins of lethality in fusion-negative rhabdomyosarcoma, we analysed single-cell transcriptomic profiles and validated our findings using nuclear RNA-sequencing, chromatin accessibility assays, spatial transcriptomics, functional perturbation studies, and external datasets. Our findings highlight a common high-risk cell state that transcends traditional subtype classifications in rhabdomyosarcoma and may inform future therapeutic targeting strategies.\n","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008318","title":"Targeted_NanoSeq__SLE_","description":"Exploring the somatic mutation landscape of SLE.","abstract":"Exploring the somatic mutation landscape of SLE.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008319","title":"H3Africa - Deciphering Developmental Disorders in Africa","description":"Developmental disorders are typically rare conditions, causing an impairment in physical, learning, language, or behavioural areas. Genetic heterogeneity and highly variable clinical manifestations make diagnosing developmental disorders particularly challenging. Developmental disorders are increasing in prevalence in low- and middle-income countries, partly due to effective prevention and treatment of infectious diseases leading to a decrease in childhood mortality.\nNew sequencing technologies are used effectively in the diagnosis of rare diseases and results can impact clinical practice significantly. \n\nDespite this international trend, very little implementation of these new approaches has taken place in low-resource settings, especially in Africa. The Deciphering Developmental Disorders in Africa (DDD-Africa) study aims to take advantage of an unbiased genotype-driven approach to improve healthcare services for patients. The study aims to recruit and perform detailed clinical phenotyping and exome sequencing (ES) on 500 African patients with a developmental disorder in whom a genetic diagnosis has not been confirmed. Where available, parents are also included in sequencing efforts.\n\nThe project has two active research sites in Johannesburg (South Africa) and Kinshasa (Democratic Republic of Congo) representing diversity in geography, clinical, socio-economic, genetic and environmental factors.","abstract":"Developmental disorders are typically rare conditions, causing an impairment in physical, learning, language, or behavioural areas. Genetic heterogeneity and highly variable clinical manifestations make diagnosing developmental disorders particularly challenging. Developmental disorders are increasing in prevalence in low- and middle-income countries, partly due to effective prevention and treatment of infectious diseases leading to a decrease in childhood mortality.\nNew sequencing technologies are used effectively in the diagnosis of rare diseases and results can impact clinical practice significantly. \n\nDespite this international trend, very little implementation of these new approaches has taken place in low-resource settings, especially in Africa. The Deciphering Developmental Disorders in Africa (DDD-Africa) study aims to take advantage of an unbiased genotype-driven approach to improve healthcare services for patients. The study aims to recruit and perform detailed clinical phenotyping and exome sequencing (ES) on 500 African patients with a developmental disorder in whom a genetic diagnosis has not been confirmed. Where available, parents are also included in sequencing efforts.\n\nThe project has two active research sites in Johannesburg (South Africa) and Kinshasa (Democratic Republic of Congo) representing diversity in geography, clinical, socio-economic, genetic and environmental factors.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-23T07:08:51+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008320","title":"Targeted_NanoSeq__Carotid_Atheroma_","description":"Exploring the somatic mutation landscape of carotid atheroma.","abstract":"Exploring the somatic mutation landscape of carotid atheroma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008321","title":"Integrative spatial and multi-omic profiling in bladder cancer links L1 retrotransposition to extrachromosomal DNA, genomic instability, and viral mimicry response","description":"Bladder cancer is one of the most frequent cancers and shows high recurrence rates. Despite recent advances, key knowledge gaps remain in understanding the molecular mechanisms of disease progression, which would support the development of early detection methods and effective personalized treatments. We apply integrated multi-omics and spatial analyses in a cohort of 49 bladder cancer patients to comprehensively profile genetic, epigenetic, transcriptomic, and spatial features of bladder cancer, alongside cell-free DNA blood analysis. Combining low-pass whole-genome cell-free DNA sequencing, Oxford Nanopore long-read tumor DNA sequencing, RNA-sequencing, and spatial transcriptomics, we provide insights into molecular alterations driving bladder cancer. We show frequent somatic LINE-1 (L1) insertions, with up to more than 500 insertions per tumor. We find that L1 insertions are active and occur early in bladder cancer development. We link aberrant somatic L1 insertion in bladder cancer with downstream genomic rearrangements and chromosomal instability, with an excess of structural variants and extrachromosomal DNA (ecDNA) in patients with particularly high L1 counts. By detecting ecDNA within tissue architecture using spatial transcriptomics, we identify the localization of ecDNA to distinct spatial clusters with differential expression of APOBEC3B and immune response pathways. These results, combined with replication timing analysis and gene set enrichment analysis (GSEA), offer evidence for the previously hypothesized viral mimicry response to L1 retrotransposition, mediated via APOBEC3B-editing, the cGAS-STING pathway, and RIG-I and MDA5 responses.","abstract":"Bladder cancer is one of the most frequent cancers and shows high recurrence rates. Despite recent advances, key knowledge gaps remain in understanding the molecular mechanisms of disease progression, which would support the development of early detection methods and effective personalized treatments. We apply integrated multi-omics and spatial analyses in a cohort of 49 bladder cancer patients to comprehensively profile genetic, epigenetic, transcriptomic, and spatial features of bladder cancer, alongside cell-free DNA blood analysis. Combining low-pass whole-genome cell-free DNA sequencing, Oxford Nanopore long-read tumor DNA sequencing, RNA-sequencing, and spatial transcriptomics, we provide insights into molecular alterations driving bladder cancer. We show frequent somatic LINE-1 (L1) insertions, with up to more than 500 insertions per tumor. We find that L1 insertions are active and occur early in bladder cancer development. We link aberrant somatic L1 insertion in bladder cancer with downstream genomic rearrangements and chromosomal instability, with an excess of structural variants and extrachromosomal DNA (ecDNA) in patients with particularly high L1 counts. By detecting ecDNA within tissue architecture using spatial transcriptomics, we identify the localization of ecDNA to distinct spatial clusters with differential expression of APOBEC3B and immune response pathways. These results, combined with replication timing analysis and gene set enrichment analysis (GSEA), offer evidence for the previously hypothesized viral mimicry response to L1 retrotransposition, mediated via APOBEC3B-editing, the cGAS-STING pathway, and RIG-I and MDA5 responses.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008322","title":"ARHGAP11A Maintains Cortical Progenitor Identity Through RHOA–ROCK Signalling During Human Brain Development","description":"Mammalian brain development involves coordinated progenitor amplification, migration, and differentiation. Apical progenitors (APs) establish the ventricular zone (VZ) and are key determinants of brain size and complexity. Rho-family guanosine triphosphatases (Rho GTPases) regulate cytoskeletal dynamics and AP behaviour, but how specific Rho GTPase-activating proteins (Rho GAPs) influence progenitor identity and VZ architecture remains unclear. Using human forebrain organoids, we investigated the Rho GAP ARHGAP11A in human corticogenesis. CRISPR/Cas9-mediated ARHGAP11A knockout revealed its essential role in maintaining VZ integrity. Loss of ARHGAP11A impaired neuroepithelial organisation and randomised mitotic cleavage plane orientation via the RHOA–ROCK–actin axis. This led to premature AP delamination, AP depletion, and reduced cell density and glial numbers. Pharmacological inhibition of RHOA or ROCK rescued these defects, highlighting ARHGAP11A’s role in cytoskeletal remodelling to maintain cortical progenitors. Our findings establish ARHGAP11A as a critical regulator of AP identity and VZ integrity, with broad implications for human corticogenesis.","abstract":"Mammalian brain development involves coordinated progenitor amplification, migration, and differentiation. Apical progenitors (APs) establish the ventricular zone (VZ) and are key determinants of brain size and complexity. Rho-family guanosine triphosphatases (Rho GTPases) regulate cytoskeletal dynamics and AP behaviour, but how specific Rho GTPase-activating proteins (Rho GAPs) influence progenitor identity and VZ architecture remains unclear. Using human forebrain organoids, we investigated the Rho GAP ARHGAP11A in human corticogenesis. CRISPR/Cas9-mediated ARHGAP11A knockout revealed its essential role in maintaining VZ integrity. Loss of ARHGAP11A impaired neuroepithelial organisation and randomised mitotic cleavage plane orientation via the RHOA–ROCK–actin axis. This led to premature AP delamination, AP depletion, and reduced cell density and glial numbers. Pharmacological inhibition of RHOA or ROCK rescued these defects, highlighting ARHGAP11A’s role in cytoskeletal remodelling to maintain cortical progenitors. Our findings establish ARHGAP11A as a critical regulator of AP identity and VZ integrity, with broad implications for human corticogenesis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-09-24T10:45:52+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008323","title":"Addenbrookes_Paediatric_Tumour_G17228_Wellcome_Core_Emseq","description":"This child was diagnosed and succumbed to a stage 4S Neuroblastoma, these usually have an extremely good prognosis however in this case, uniquely presented with aggressive disease. This presents us with the opportunity to establish if the stage 4S disease was metastatic or had synchronous primary tumours, as well as analysis regarding the genetic relationship between normal and tumour.  Emseq study.","abstract":"This child was diagnosed and succumbed to a stage 4S Neuroblastoma, these usually have an extremely good prognosis however in this case, uniquely presented with aggressive disease. This presents us with the opportunity to establish if the stage 4S disease was metastatic or had synchronous primary tumours, as well as analysis regarding the genetic relationship between normal and tumour.  Emseq study.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008324","title":"Machine Learning Uncovers Previously Undetectable Genetic Deletions in Cancer Panel Sequencing","description":"We developed a novel machine-learning pipeline for detection of genetic deletions and zygosity evaluation within MASTERsg, a precision oncology program using the TSO500 DNA gene panel to identify targetable alterations in advanced cancers. The TSO500 pipeline detects copy number variations (CNVs) through bin count averaging but may miss focal CNVs not meeting thresholds. As a proof-of-concept we used deletions in PTEN, which confer sensitivity to mTOR and Akt inhibition. An Extreme Gradient Boosting model trained on tumor samples with PTEN deletions and PTEN wild-type status enabled the correct identification of missed focal deletions, which were subsequently confirmed by immunohistochemistry. Additional cases of PTEN loss could be identified in 34 of 204 previously profiled, seemingly uneventful samples, which were validated in 75% of stainable cases. The findings underscore the substantial clinical potential of this method to uncover therapeutically relevant alterations beyond established diagnostic pipelines.","abstract":"We developed a novel machine-learning pipeline for detection of genetic deletions and zygosity evaluation within MASTERsg, a precision oncology program using the TSO500 DNA gene panel to identify targetable alterations in advanced cancers. The TSO500 pipeline detects copy number variations (CNVs) through bin count averaging but may miss focal CNVs not meeting thresholds. As a proof-of-concept we used deletions in PTEN, which confer sensitivity to mTOR and Akt inhibition. An Extreme Gradient Boosting model trained on tumor samples with PTEN deletions and PTEN wild-type status enabled the correct identification of missed focal deletions, which were subsequently confirmed by immunohistochemistry. Additional cases of PTEN loss could be identified in 34 of 204 previously profiled, seemingly uneventful samples, which were validated in 75% of stainable cases. The findings underscore the substantial clinical potential of this method to uncover therapeutically relevant alterations beyond established diagnostic pipelines.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008325","title":"CG_Reproductive_A_MV_EndoBH_Spatial_Vento_Managed","description":"A collaborative multi-institute project, using single cell atlasing and spatial techniques on endometrium samples and endometriosis cases to investigate endometriosis disease mechanisms, and endometrial cell biology (BH = 22/0009 - Oxford).","abstract":"A collaborative multi-institute project, using single cell atlasing and spatial techniques on endometrium samples and endometriosis cases to investigate endometriosis disease mechanisms, and endometrial cell biology (BH = 22/0009 - Oxford).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008326","title":"WGS, DuplexSeq and NanoSeq genomic data from histologically normal tissue in cancer patients","description":"The extent to which mutagenic and non-mutagenic processes, including cancer treatment, contribute to somatic evolution in histologically normal tissue remains unclear. We subjected 168 cancer-free normal samples representing 16 different organs from 22 patients with metastatic cancer enrolled in the PEACE research autopsy study to high-depth duplex panel sequencing (coverage &gt;20,000x). In every sample we identified somatic mutations (range 170 - 2,978) at exceedingly low variant allele frequencies (median VAF 0.0000323), consistent with a patchwork of mutated cells in normal tissue. By analysing the mutational spectra of each sample, we extracted 16 distinct single base substitution mutational signatures, reflecting somatic mutational processes that have moulded the genomes of normal cells. Signatures were found to be associated with diverse aetiologies, including alcohol-related mutation acquisition in liver tissue, smoking-induced mutagenesis in lung and cardiac tissue, and multiple distinct treatment-induced processes, which correlated with treatment and its duration. On average, in this cohort in which patients had each received several lines of anti-cancer therapy, exogenous sources, including treatment-related mutagenesis, underpinned &gt;40% of mutations in liver samples, yet &lt;10% in brain samples. Finally, we observed clear differences in the extent and effects of selection in different tissues, with positive selection in certain tissues, including lung (TP53, EGFR and PIK3CA), liver (NF2L2) and spleen (BRAF, NOTCH2), and limited selection in others, such as brain and cardiac. Over 25% of driver mutations in normal tissue exposed to systemic anti-cancer therapy, including mutations in TP53, could be attributed to treatment-induced mutagenesis. Immunotherapy, while not associated with mutagenesis, was linked to an excess of driver mutations in PPM1D and TP53, illustrating how non-mutagenic treatment can sculpt somatic evolution. Our study reveals the rich tapestry of mutational processes and driver mutations in cancer-free normal tissue, and the profound impact of cancer therapeutic and life-time environmental exposures on normal tissue somatic evolution.","abstract":"The extent to which mutagenic and non-mutagenic processes, including cancer treatment, contribute to somatic evolution in histologically normal tissue remains unclear. We subjected 168 cancer-free normal samples representing 16 different organs from 22 patients with metastatic cancer enrolled in the PEACE research autopsy study to high-depth duplex panel sequencing (coverage &gt;20,000x). In every sample we identified somatic mutations (range 170 - 2,978) at exceedingly low variant allele frequencies (median VAF 0.0000323), consistent with a patchwork of mutated cells in normal tissue. By analysing the mutational spectra of each sample, we extracted 16 distinct single base substitution mutational signatures, reflecting somatic mutational processes that have moulded the genomes of normal cells. Signatures were found to be associated with diverse aetiologies, including alcohol-related mutation acquisition in liver tissue, smoking-induced mutagenesis in lung and cardiac tissue, and multiple distinct treatment-induced processes, which correlated with treatment and its duration. On average, in this cohort in which patients had each received several lines of anti-cancer therapy, exogenous sources, including treatment-related mutagenesis, underpinned &gt;40% of mutations in liver samples, yet &lt;10% in brain samples. Finally, we observed clear differences in the extent and effects of selection in different tissues, with positive selection in certain tissues, including lung (TP53, EGFR and PIK3CA), liver (NF2L2) and spleen (BRAF, NOTCH2), and limited selection in others, such as brain and cardiac. Over 25% of driver mutations in normal tissue exposed to systemic anti-cancer therapy, including mutations in TP53, could be attributed to treatment-induced mutagenesis. Immunotherapy, while not associated with mutagenesis, was linked to an excess of driver mutations in PPM1D and TP53, illustrating how non-mutagenic treatment can sculpt somatic evolution. Our study reveals the rich tapestry of mutational processes and driver mutations in cancer-free normal tissue, and the profound impact of cancer therapeutic and life-time environmental exposures on normal tissue somatic evolution.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008327","title":"Transcriptional_changes_in_blood_after_chemotherapy","description":"We are studying changes in the mutational landscape in blood before and after chemotherapy.  To complement this we wish to perform RNAseq on the same samples to try and assess changes in cell populations as well as the transcriptome.","abstract":"We are studying changes in the mutational landscape in blood before and after chemotherapy.  To complement this we wish to perform RNAseq on the same samples to try and assess changes in cell populations as well as the transcriptome.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008328","title":"DERMATLAS__OHSU_tumour_case_study_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The case in this cohort is an unusual presentation of a basaloid tumour.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The case in this cohort is an unusual presentation of a basaloid tumour.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-10-01T16:04:12+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008329","title":"DERMATLAS__OHSU_tumour_case_study_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The case in this cohort is an unusual presentation of a basaloid tumour.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The case in this cohort is an unusal presentation of a basaloid tumour.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-10-01T16:07:57+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008330","title":"The ITCC-P4 PDX platform of pediatric cancers for preclinical testing","description":"Cancer is the leading cause of disease-related deaths among children in high-income countries. Tumor heterogeneity and lack of mechanism-of-action-based therapeutic options are key challenges to overcome in order to improve pediatric cancer patients’ survival. Here, we report the EU-IMI-2 funded public-private partnership “ITCC-Pediatric Preclinical Proof-of-Concept Platform” (ITCC-P4), which has built a large repertoire of patient-derived xenograft (PDX) models, representing all major solid pediatric cancer types, for in vivo drug testing. Three-hundred-fifty-three PDX models from diagnostic and relapsed pediatric cancers have been established and molecularly characterized, together with matched germline/tumor samples. As proof-of-concept, we present in vivo drug screening data in neuroblastoma and rhabdomyosarcoma models. PDX data, accessible at http://r2platform.com/itcc-p4, allow the selection of models based on oncogenic drivers and/or potential biomarkers for preclinical testing. Operated by a non-profit entity (www.itccp4.com), this sustainable platform aids academic and industrial researchers in developing and prioritizing innovative therapies for pediatric cancer.","abstract":"Cancer is the leading cause of disease-related deaths among children in high-income countries. Tumor heterogeneity and lack of mechanism-of-action-based therapeutic options are key challenges to overcome in order to improve pediatric cancer patients’ survival. Here, we report the EU-IMI-2 funded public-private partnership “ITCC-Pediatric Preclinical Proof-of-Concept Platform” (ITCC-P4), which has built a large repertoire of patient-derived xenograft (PDX) models, representing all major solid pediatric cancer types, for in vivo drug testing. Three-hundred-fifty-three PDX models from diagnostic and relapsed pediatric cancers have been established and molecularly characterized, together with matched germline/tumor samples. As proof-of-concept, we present in vivo drug screening data in neuroblastoma and rhabdomyosarcoma models. PDX data, accessible at http://r2platform.com/itcc-p4, allow the selection of models based on oncogenic drivers and/or potential biomarkers for preclinical testing. Operated by a non-profit entity (www.itccp4.com), this sustainable platform aids academic and industrial researchers in developing and prioritizing innovative therapies for pediatric cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-10-02T12:47:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008331","title":"sWGS of Neo-RT plasma cfDNA","description":"Neo-RT (NCT03818100) is a non-randomised, single-arm feasibility study of neoadjuvant radiotherapy and endocrine therapy in women with ER+, HER2-breast cancer that is grade 1 or 2 (grade 3 was allowed if chemotherapy contraindicated), with palpable size equal to or greater than 20mm, such that radiotherapy may facilitate BCS.","abstract":"Neo-RT (NCT03818100) is a non-randomised, single-arm feasibility study of neoadjuvant radiotherapy and endocrine therapy in women with ER+, HER2-breast cancer that is grade 1 or 2 (grade 3 was allowed if chemotherapy contraindicated), with palpable size equal to or greater than 20mm, such that radiotherapy may facilitate BCS.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008332","title":"Single-cell and spatial transcriptomic profiling of hormone-naïve localised prostate cancer","description":"Localised prostate cancers (PCa) are heterogeneous and multifocal, with diverse outcomes. Current prognostic methods are epithelium-centric, overlooking the complex cellular landscape within the tumour microenvironment (TME), which remains incompletely characterised. We performed a comprehensive analysis of cancerous and adjacent-benign cores from 24 patients with hormone therapy-naïve localised PCa using single-cell RNA-sequencing. By integrating copy number variation and transcriptional signatures, we classified epithelial cells across a malignant spectrum, revealing widespread molecular perturbation. We found an expansion of Club cell phenotypes, suggestive of Luminal dedifferentiation. We also performed a detailed annotation of stromal phenotypes, focusing on fibroblasts, and identified a novel peri-neural fibroblast population. Spatial transcriptomics elucidated the precise anatomical distribution of CAFs within the PCa TME. This study provides a valuable foundation for advancing our understanding of PCa pathobiology and developing a comprehensive cellular model of the disease.","abstract":"Localised prostate cancers (PCa) are heterogeneous and multifocal, with diverse outcomes. Current prognostic methods are epithelium-centric, overlooking the complex cellular landscape within the tumour microenvironment (TME), which remains incompletely characterised. We performed a comprehensive analysis of cancerous and adjacent-benign cores from 24 patients with hormone therapy-naïve localised PCa using single-cell RNA-sequencing. By integrating copy number variation and transcriptional signatures, we classified epithelial cells across a malignant spectrum, revealing widespread molecular perturbation. We found an expansion of Club cell phenotypes, suggestive of Luminal dedifferentiation. We also performed a detailed annotation of stromal phenotypes, focusing on fibroblasts, and identified a novel peri-neural fibroblast population. Spatial transcriptomics elucidated the precise anatomical distribution of CAFs within the PCa TME. This study provides a valuable foundation for advancing our understanding of PCa pathobiology and developing a comprehensive cellular model of the disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-10-05T23:20:43+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008333","title":"Leukaemia_Cambridge_Behjati_WellcomeCore_Targeted_Nanoseq_TE_91275970","description":"Targeted nanosequencing of childhood leukaemias\nWe have a large, expanding,  cohort of childhood leukaemias, from Great Ormond Street Hospital, in London, who have undergone scRNA sequencing +/- WGS. To better understand the clonal composition and evolution of these cancers we are planning to use targeted nanosequencing. Over different treatment timepoints we aim to understand which genes are under selection and are the bottlenecks for the development of deadly clones. Alongside this we aim to study mutation in normal tissues, as these children undergo treatment with mutagenic chemotherapy. ","abstract":"Targeted nanosequencing of childhood leukaemias\nWe have a large, expanding,  cohort of childhood leukaemias, from Great Ormond Street Hospital, in London, who have undergone scRNA sequencing +/- WGS. To better understand the clonal composition and evolution of these cancers we are planning to use targeted nanosequencing. Over different treatment timepoints we aim to understand which genes are under selection and are the bottlenecks for the development of deadly clones. Alongside this we aim to study mutation in normal tissues, as these children undergo treatment with mutagenic chemotherapy. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008334","title":"Whole_exome_sequencing_of_Severe_Insulin_Resistant_patients_inactive_","description":"Illumina paired-end sequencing of whole- exome pulldown DNA from Severe Insulin Resistant patients.","abstract":"Over the last 10 years or so candidate gene re-sequencing in individuals with severe insulin resistance syndromes has led to the discovery of genes (e.g. INSR, LMNA, PPARG, AKT2, PPP1R3, CIDEC, AS160, etc)  that when mutated are causative of those particular phenotypes. However, many insulin resistant patients exist for whom the underlying causative mutation(s) remains unknown.  We have initiated a study targeted at re-sequencing the whole exome in a subset of individuals selected on the basis of their phenotype and likely mode of inheritance in an attempt to identify additional likely causal variants.  Candidate causal variants will be confirmed by follow-up co-segregation analysis in affected families and further analysis in additional cases and/or downstream functional and clinical follow up.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008335","title":"CG_Multi_P_iPSC_WGS_Nanoseq_Behjati","description":"Human iPSC cell line study","abstract":"Human iPSC cell line study","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-10-08T16:23:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008336","title":"Foetal_Macrophage_Ontogeny___Targeted","description":"The origins of different tissue macrophages will be characterized by mutational analyses of targeted sequencing data created from sorted cells. Samples have been sourced from Newcastle.","abstract":"The origins of different tissue macrophages will be characterized by mutational analyses of targeted sequencing data created from sorted cells. Samples have been sourced from Newcastle.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008337","title":"DecodeME: The World’s Largest ME/CFS Study","description":"Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a common, disabling illness. It affects more females than males, and in most cases, starts after an infection. Little is known about the biological mechanisms that cause ME/CFS, despite many attempts to uncover them, and it has no effective treatments.\n \nTo understand ME/CFS better, our study, DecodeME, compared the DNA of 15,579 people with ME/CFS with the DNA of 259,909 people without ME/CFS, all of European descent. DNA is a molecule that makes up our genes. Our genes make many different molecules called proteins, each of which does very specific things in the body. Finding variations in genes that differ between people with or without a disease can therefore point to what causes it.\n \nWe found that people with ME/CFS are more likely to carry certain DNA differences in eight regions of their genome, and so these variants tell us about possible biological causes of ME/CFS. However, as these differences are also often found in people without ME/CFS they cannot cleanly separate who is at risk and who is not, and therefore do not provide a definitive test. Most of these regions contain several genes.\n \nOur methods did not allow us to conclusively locate the ones most relevant to ME/CFS in each region, but public data allowed us to pick out the most likely ones. Three of the most likely genes produce proteins that respond to an infection. Another likely gene is related to chronic pain. None are related to depression or anxiety. We found nothing to explain why more females than males get ME/CFS.\n \nOverall, DecodeME shows that ME/CFS is partly caused by genes related to the immune and nervous systems.","abstract":"Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a common, disabling illness. It affects more females than males, and in most cases, starts after an infection. Little is known about the biological mechanisms that cause ME/CFS, despite many attempts to uncover them, and it has no effective treatments.\n \nTo understand ME/CFS better, our study, DecodeME, compared the DNA of 15,579 people with ME/CFS with the DNA of 259,909 people without ME/CFS, all of European descent. DNA is a molecule that makes up our genes. Our genes make many different molecules called proteins, each of which does very specific things in the body. Finding variations in genes that differ between people with or without a disease can therefore point to what causes it.\n \nWe found that people with ME/CFS are more likely to carry certain DNA differences in eight regions of their genome, and so these variants tell us about possible biological causes of ME/CFS. However, as these differences are also often found in people without ME/CFS they cannot cleanly separate who is at risk and who is not, and therefore do not provide a definitive test. Most of these regions contain several genes.\n \nOur methods did not allow us to conclusively locate the ones most relevant to ME/CFS in each region, but public data allowed us to pick out the most likely ones. Three of the most likely genes produce proteins that respond to an infection. Another likely gene is related to chronic pain. None are related to depression or anxiety. We found nothing to explain why more females than males get ME/CFS.\n \nOverall, DecodeME shows that ME/CFS is partly caused by genes related to the immune and nervous systems.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-10-13T16:18:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008338","title":"Lung Cohort for the UNITE study","description":"Lung Cohort for the UNITE study","abstract":"Lung Cohort for the UNITE study","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008339","title":"Stratton__Somatic_mutations_in_benign_and_malignant_kidney_diseases___LCMB_WGS","description":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. Here, we will study somatic mutations in benign and malignant kidney tissue samples, including their matched normal tissues, to better understand mutational signatures, burdens, driver selection within these conditions. ","abstract":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. \n\nSomatic mutational profiles in oligomutated and polyclonal tissues such as the kidney have not been well studied using whole-genome sequencing as it has been previously cost-prohibitive due to the sequencing error rates of WGS. This study will focus on applying duplex sequencing to study benign and malignant kidney conditions, and also apply WGS and whole-exome sequencing to study possible clonal populations within the kidneys (and their matched controls such as blood).   ","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008340","title":"Stratton__Somatic_mutations_in_benign_and_malignant_kidney_diseases___DupSeq","description":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. \n\nHere, we will study somatic mutations in benign and malignant kidney tissue samples, including their matched normal tissues, to better understand mutational signatures, burdens, driver selection within these conditions. ","abstract":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. \n\nSomatic mutational profiles in oligomutated and polyclonal tissues such as the kidney have not been well studied using whole-genome sequencing as it has been previously cost-prohibitive due to the sequencing error rates of WGS. This study will focus on applying duplex sequencing to study benign and malignant kidney conditions, and also apply WGS and whole-exome sequencing to study possible clonal populations within the kidneys (and their matched controls such as blood).   ","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008341","title":"Stratton__Somatic_mutations_in_benign_and_malignant_kidney_diseases_WES","description":"he Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. Here, we will study somatic mutations in benign and malignant kidney tissue samples, including their matched normal tissues, to better understand mutational signatures, burdens, driver selection within these conditions. ","abstract":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. \n\nSomatic mutational profiles in oligomutated and polyclonal tissues such as the kidney have not been well studied using whole-genome sequencing as it has been previously cost-prohibitive due to the sequencing error rates of WGS. This study will focus on applying duplex sequencing to study benign and malignant kidney conditions, and also apply WGS and whole-exome sequencing to study possible clonal populations within the kidneys (and their matched controls such as blood).   ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008342","title":"CG_A_CRC_RNA_OTAR_3092_Managed","description":"Single-cell RNA-sequencing to identify the cell populations composing CRC.","abstract":"\"Single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (STx) offer an unprecedented opportunity to identify the cell populations composing CRC and to map in great detail how transcriptomic states change in spatial cell-to-cell interactions of immune and tumour cells, and also between cytolytic and regulatory immune cell types. Furthermore, STx technologies offer the possibility to examine distribution of different cancer clones (2) in CRC and their interactions with diverse immune cells. This will provide vital data about the clonal structure of CRC in response to immunogenic control and a unique opportunity to evaluate the performance and interaction of putative targets within different CRC clones.\n\"","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008343","title":"Ovarian Cohort for the UNITE study","description":"Ovarian Cohort for the UNITE study\t","abstract":"Ovarian Cohort for the UNITE study\t","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008344","title":"CG_Reproductive_A_DM_Site_1_RNA_LEAP_MVS_Managed","description":"\"LEAP-MVS_DM_Site1 - Understanding the heterogeneity of reproduction related tissues by multi-level analyses and organoid and\ncell line derivation\"","abstract":"\"LEAP-MVS_DM_Site1 - Understanding the heterogeneity of reproduction related tissues by multi-level analyses and organoid and\ncell line derivation\"","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008345","title":"Noorani_UGI_EVT_10X","description":"Analysis of endoluminal vacuum therapy sponges from patients with oesophageal perforations or anastomotic leak to assess oesophageal healing.","abstract":"NOORANI_UGI_EVT_10X","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008346","title":"European BestAgeing Study on microRNA candidates for cardiovascular disease","description":"Background: Circulating miRNAs have emerged as promising biomarker candidates due to their stability and their role in regulating key pathological pathways in cardiovascular disease (CVD). Yet, large-scale, multicenter studies examining their diagnostic and prognostic potential are scarce. This study evaluates the potential of miRNA expression profiles to inform disease classification and risk stratification across major CVD phenotypes, including acute coronary syndrome (ACS), chronic coronary artery disease (CAD), dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM), in a large, multicenter European cohort.\nMethods: We assessed genome-wide miRNA expression profiles in a total of 1,209 cardiovascular patients and 848 controls in a uniform, standardized fashion, which renders this study one of the largest prospective miRNA studies. To focus on only the most biologically plausible miRNAs for clinical translation, we mined all original studies of miRNA candidates in CVD and performed differential miRNA expression and enrichment analysis. We then trained disease-specific binary classification models to evaluate the diagnostic potential of miRNA signatures. Finally, we evaluated prognosis and disease severity based on distinct miRNA levels. \nResults: 634 original abstracts were identified, detailing 166 ACS, 181 CAD, 56 DCM, and 182 ICM miRNAs. Without further optimization, the signatures of a priori miRNAs already yielded very good diagnostic performance with ROC AUC of 0.83 – 0.95. There was an improvement when considering additional miRNAs in a discovery setting. Interestingly, in ACS, CAD and DCM we observed a significantly worse prognosis in probands with higher scores in the miRNA signatures, indicating additional prognostic information.\nConclusions: The European BestAgeing miRNA study reveals emerging associations of several miRNA signatures with cardiovascular disease discrimination and prognostication, providing a foundation for future external validation and potential clinical translation of this class of markers. ","abstract":"Background: Circulating miRNAs have emerged as promising biomarker candidates due to their stability and their role in regulating key pathological pathways in cardiovascular disease (CVD). Yet, large-scale, multicenter studies examining their diagnostic and prognostic potential are scarce. This study evaluates the potential of miRNA expression profiles to inform disease classification and risk stratification across major CVD phenotypes, including acute coronary syndrome (ACS), chronic coronary artery disease (CAD), dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM), in a large, multicenter European cohort.\nMethods: We assessed genome-wide miRNA expression profiles in a total of 1,209 cardiovascular patients and 848 controls in a uniform, standardized fashion, which renders this study one of the largest prospective miRNA studies. To focus on only the most biologically plausible miRNAs for clinical translation, we mined all original studies of miRNA candidates in CVD and performed differential miRNA expression and enrichment analysis. We then trained disease-specific binary classification models to evaluate the diagnostic potential of miRNA signatures. Finally, we evaluated prognosis and disease severity based on distinct miRNA levels. \nResults: 634 original abstracts were identified, detailing 166 ACS, 181 CAD, 56 DCM, and 182 ICM miRNAs. Without further optimization, the signatures of a priori miRNAs already yielded very good diagnostic performance with ROC AUC of 0.83 – 0.95. There was an improvement when considering additional miRNAs in a discovery setting. Interestingly, in ACS, CAD and DCM we observed a significantly worse prognosis in probands with higher scores in the miRNA signatures, indicating additional prognostic information.\nConclusions: The European BestAgeing miRNA study reveals emerging associations of several miRNA signatures with cardiovascular disease discrimination and prognostication, providing a foundation for future external validation and potential clinical translation of this class of markers. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-10-27T09:59:40+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008347","title":"Genetic and Genomic Landscape of Hemochromatosis Hepatocellular Carcinoma","description":"Hemochromatosis is a Mendelian genetic disorder characterized by systemic iron overload, which increases the risk of developing hepatocellular carcinoma (HCC). This study aims to investigate the genetic and molecular mechanisms underlying HCC in patients with hemochromatosis, to improve understanding of disease progression and identify potential therapeutic targets","abstract":"Hemochromatosis is a Mendelian genetic disorder characterized by systemic iron overload, which increases the risk of developing hepatocellular carcinoma (HCC). This study aims to investigate the genetic and molecular mechanisms underlying HCC in patients with hemochromatosis, to improve understanding of disease progression and identify potential therapeutic targets","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008348","title":"CD4_co_stim_CRISPR_screen","description":"CD4 T cells will be isolated from blood of healthy individuals. The cells will be edited in vitro through transduction of a pooled lentiviral library (to introduce dual guide RNA to the cells) and Cas9 protein electroporated at day 2 and day 3, respectively. Under puromycin selection, cells will be expanded until day 10. At day 10, cells will be stimulated (modified B cell line or commercial reagents) for roughly 3 days. At this point, CD4 T cells will be sorted based on their phenotypic profile. Pooled CRISPR library will be generated by amplifying guideRNA using 2 step PCR process. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Lymphocytes are key in the adaptive immune response but genetic knowledge in these cell types roles remain somewhat unexplored. This project aims to seek for gene hits involved in specific lymphocytic function to drawing a detailed map in the mechanisms underpinning immune cell phenotypes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008349","title":"European BestAgeing Study on microRNA candidates for cardiovascular disease","description":"Background: Circulating miRNAs have emerged as promising biomarker candidates due to their stability and their role in regulating key pathological pathways in cardiovascular disease (CVD). Yet, large-scale, multicenter studies examining their diagnostic and prognostic potential are scarce. This study evaluates the potential of miRNA expression profiles to inform disease classification and risk stratification across major CVD phenotypes, including acute coronary syndrome (ACS), chronic coronary artery disease (CAD), dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM), in a large, multicenter European cohort.\nMethods: We assessed genome-wide miRNA expression profiles in a total of 1,209 cardiovascular patients and 848 controls in a uniform, standardized fashion, which renders this study one of the largest prospective miRNA studies. To focus on only the most biologically plausible miRNAs for clinical translation, we mined all original studies of miRNA candidates in CVD and performed differential miRNA expression and enrichment analysis. We then trained disease-specific binary classification models to evaluate the diagnostic potential of miRNA signatures. Finally, we evaluated prognosis and disease severity based on distinct miRNA levels. \nResults: 634 original abstracts were identified, detailing 166 ACS, 181 CAD, 56 DCM, and 182 ICM miRNAs. Without further optimization, the signatures of a priori miRNAs already yielded very good diagnostic performance with ROC AUC of 0.83 – 0.95. There was an improvement when considering additional miRNAs in a discovery setting. Interestingly, in ACS, CAD and DCM we observed a significantly worse prognosis in probands with higher scores in the miRNA signatures, indicating additional prognostic information.\nConclusions: The European BestAgeing miRNA study reveals emerging associations of several miRNA signatures with cardiovascular disease discrimination and prognostication, providing a foundation for future external validation and potential clinical translation of this class of markers. ","abstract":"Background: Circulating miRNAs have emerged as promising biomarker candidates due to their stability and their role in regulating key pathological pathways in cardiovascular disease (CVD). Yet, large-scale, multicenter studies examining their diagnostic and prognostic potential are scarce. This study evaluates the potential of miRNA expression profiles to inform disease classification and risk stratification across major CVD phenotypes, including acute coronary syndrome (ACS), chronic coronary artery disease (CAD), dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM), in a large, multicenter European cohort.\nMethods: We assessed genome-wide miRNA expression profiles in a total of 1,209 cardiovascular patients and 848 controls in a uniform, standardized fashion, which renders this study one of the largest prospective miRNA studies. To focus on only the most biologically plausible miRNAs for clinical translation, we mined all original studies of miRNA candidates in CVD and performed differential miRNA expression and enrichment analysis. We then trained disease-specific binary classification models to evaluate the diagnostic potential of miRNA signatures. Finally, we evaluated prognosis and disease severity based on distinct miRNA levels. \nResults: 634 original abstracts were identified, detailing 166 ACS, 181 CAD, 56 DCM, and 182 ICM miRNAs. Without further optimization, the signatures of a priori miRNAs already yielded very good diagnostic performance with ROC AUC of 0.83 – 0.95. There was an improvement when considering additional miRNAs in a discovery setting. Interestingly, in ACS, CAD and DCM we observed a significantly worse prognosis in probands with higher scores in the miRNA signatures, indicating additional prognostic information.\nConclusions: The European BestAgeing miRNA study reveals emerging associations of several miRNA signatures with cardiovascular disease discrimination and prognostication, providing a foundation for future external validation and potential clinical translation of this class of markers. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008350","title":"Transcriptomic Study of Alcohol Liver Disease","description":"The dataset provides gene expression profiles to elucidate molecular mechanisms underlying alcohol related liver disease in non-tumor and tumor liver (hepatocellular carcinoma) samples","abstract":"The dataset provides gene expression profiles to elucidate molecular mechanisms underlying alcohol related liver disease in non-tumor and tumor liver (hepatocellular carcinoma) samples","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008351","title":"CG_Multi_P_iPSC_WGS_Behjati","description":"Human iPSC cell line study WGS","abstract":"Human iPSC cell line study WGS","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-10-29T11:03:48+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008352","title":"Whole-genome sequencing and transcriptome sequencing of patient tumors used for functional patient stratification in the MASTER precision oncology registry","description":"To date therapeutic decision making in rare tumors remains particularly challenging in rare tumors, where molecular profiling provides diagnostic insights but often lacks direct therapeutic consequences. we established a biopsy-compatible and scalable drug sensitivity testing platform that enables for ex vivo screening of 87 clinically relevant anti-cancer agents using minimal input. This repository provides whole-genome sequencing (WGS) and bulk RNA sequencing data from the original patient tumors of the tested samples enrolled in the MASTER trial, a precision oncology registry led by the German Cancer Research Center (DKFZ), the National Center for Tumor Diseases (NCT) Heidelberg and Dresden and the German Cancer Consortium (DKTK). The dataset enables molecular association of in vitro drug sensitivity with sequencing data from the tested sample and provides an insight into potential actionable alterations.","abstract":"To date therapeutic decision making in rare tumors remains particularly challenging in rare tumors, where molecular profiling provides diagnostic insights but often lacks direct therapeutic consequences. we established a biopsy-compatible and scalable drug sensitivity testing platform that enables for ex vivo screening of 87 clinically relevant anti-cancer agents using minimal input. This repository provides whole-genome sequencing (WGS) and bulk RNA sequencing data from the original patient tumors of the tested samples enrolled in the MASTER trial, a precision oncology registry led by the German Cancer Research Center (DKFZ), the National Center for Tumor Diseases (NCT) Heidelberg and Dresden and the German Cancer Consortium (DKTK). The dataset enables molecular association of in vitro drug sensitivity with sequencing data from the tested sample and provides an insight into potential actionable alterations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008353","title":"Endocrine therapy reprogramming of breast cancer facilitates metastatic escape via upregulation of P-Rex1/Rac1 signalling","description":"The estrogen receptor (ER) drives growth in ~70% of breast cancers, and endocrine therapies prevent recurrence. However, 30% of patients recur, with many fatal cases occurring late (after &gt;5 years), presenting a challenge due to their often non-proliferative nature and limited options. To study this, we generated slow-growing resistant cells that form small primary tumours but readily metastasize. Single-cell RNA sequencing (scRNAseq) revealed that endocrine therapy reprograms these cells, notably upregulating the Rac1 signalling component P-Rex1. We found in clinical cohorts that P-Rex1 in high in ER+ breast cancer. Intravital imaging demonstrated that Rac1 signalling is active in ER+ cells following endocrine therapy. Targeting the Rac1 pathway with small molecule inhibitors (NSC23766, R-ketorolac) reduced survival and motility in resistant cells, inhibited in vivo Rac1 activity, and reduced tumour burden when combined with tamoxifen in a drug-refractory patient-derived xenograft. This work identifies the P-Rex1/Rac1 axis, as a potential therapeutic target for late recurring ER+ breast cancer.","abstract":"The estrogen receptor (ER) drives growth in ~70% of breast cancers, and endocrine therapies prevent recurrence. However, 30% of patients recur, with many fatal cases occurring late (after &gt;5 years), presenting a challenge due to their often non-proliferative nature and limited options. To study this, we generated slow-growing resistant cells that form small primary tumours but readily metastasize. Single-cell RNA sequencing (scRNAseq) revealed that endocrine therapy reprograms these cells, notably upregulating the Rac1 signalling component P-Rex1. We found in clinical cohorts that P-Rex1 in high in ER+ breast cancer. Intravital imaging demonstrated that Rac1 signalling is active in ER+ cells following endocrine therapy. Targeting the Rac1 pathway with small molecule inhibitors (NSC23766, R-ketorolac) reduced survival and motility in resistant cells, inhibited in vivo Rac1 activity, and reduced tumour burden when combined with tamoxifen in a drug-refractory patient-derived xenograft. This work identifies the P-Rex1/Rac1 axis, as a potential therapeutic target for late recurring ER+ breast cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-11-03T01:03:06+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008354","title":"TBD_Whole_exome_NanoSeq","description":"In patients with monogenic short telomeres, somatic rescue mutations have been documented in many cases; these can arrest telomere attrition or promote elongation. We expect that deep sequencing of patients with telomere biology disorders will determine the mutational landscape associated with these disorders and also permit the discovery of novel rescue mechanisms. ","abstract":"Aim: To establish the landscape of somatic mutations in patients with telomere biology disorders\nMethods: DNA derived from peripheral blood will be sequenced using whole exome Nanoseq\nFuture studies: Candidates from this exome sequencing will be selected and more deeply sequencing using a targeted panel, and validated experimentally to determine the mechanisms of rescue. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008355","title":"Targeted_Nanoseq___Skin_Autoimmune_Diseases","description":"Skin samples with autoimmune diseases are interrogated with NanoSeq to reveal somatic mutations in lymphocytes and keratinocytes. ","abstract":"Skin autoimmune diesases comprise of many heterogeneous conditions. Recent studies of systemic autoimmune conditions identified recurrent, polyclonal somatic mutations in lymphocytes. This study asks if such mutations exist in skin autoimmune conditions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008356","title":"Skeletal_muscle_Targeted_NanoSeq","description":"Targeted NanoSeq in skeletal muscle of donors with across age and varying levels of sarcopenia.","abstract":"Investigation of the mutational landscape of sarcopenia in skeletal muscle.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008357","title":"Exome_NanoSeq_Skin_____Skin_Autoimmune_Diseases","description":"Skin samples with autoimmune diseases are interrogated with NanoSeq to reveal somatic mutations in lymphocytes and keratinocytes. ","abstract":"Skin autoimmune diesases comprise of many heterogeneous conditions. Recent studies of systemic autoimmune conditions identified recurrent, polyclonal somatic mutations in lymphocytes. This study asks if such mutations exist in skin autoimmune conditions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008358","title":"Targeted_NanoSeq___Investigating_the_clonal_dynamics_in_respiratory_tracts_with_cystic_fibrosis","description":"The aim of this project is to better understand the mutational landscape and its interaction with the microbiome in the airways from patients with cystic fibrosis. Targeted NanoSeq data will be generated by laser captured microdissection (LCM) and tissue ribboning with fresh frozen bronchus and lung parenchymal tissues. ","abstract":"Cystic fibrosis (CF) is a genetic disease leading to significant dysbiosis, particularly in the lungs. One critical cause of poor outcomes in CF patients is chronic lung infections. As a result, this project will be investigating the clonal dynamics and the interactions between mutational patterns and microbial colonisation in CF respiratory tracts using LCM, aiming to better characterise the pathophysiology and stratification of the disease. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008359","title":"Stratton__The_role_of_microbiome_derived_mutagenic_exposures_of_the_normal_colorectal_epithelium_in_causation_of_colorectal_cancer_","description":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. Here, we will study somatic mutations in benign and malignant kidney tissue samples, including their matched normal tissues, to better understand mutational signatures, burdens, driver selection within these conditions. ","abstract":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. Here, we will study somatic mutations in benign and malignant kidney tissue samples, including their matched normal tissues, to better understand mutational signatures, burdens, driver selection within these conditions. ","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008360","title":"HG_DIAMONDS_RNA","description":"The DIAMONDS (Diagnosis and Management of Febrile Illness using RNA Personalised Molecular Signature Diagnosis cohort was established to create a biobank of samples and clinical data collected from patients presenting with fever and diagnosed with diverse infectious and inflammatory conditions. To date, over 12,000 patients have been recruited across 15 countries (12 in Europe plus Nepal, Gambia and Taiwan). The cohort includes detailed phenotyping information which has been used by clinical working groups to rigorously categorise participants for example into definite viral and definite bacterial infection. The cohort is predominantly paediatric but includes vulnerable people such as pregnant women, neonates and the elderly. This biobank offers us an opportunity to generate bulk RNA-seq and blended WGS/WES data for a subset of patients to address some of the specific research questions our team are currently tackling.\nResearch questions:\n1. Is SRS group associated with more severe illness in this broader cohort which spans neonatal to elderly patients?\n2. How much does host genetics contribute to SRS group membership?\n3. Do we observe differential splicing between different infection types (or specific infections)?\n4. Can we identify examples of outlying gene expression, particularly in paediatric samples and link this to genetic variants?\n5. Can we use eQTL interactions to understand more about variation in the response to infection?\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"The DIAMONDS (Diagnosis and Management of Febrile Illness using RNA Personalised Molecular Signature Diagnosis cohort was established to create a biobank of samples and clinical data collected from patients presenting with fever and diagnosed with diverse infectious and inflammatory conditions. To date, over 12,000 patients have been recruited across 15 countries (12 in Europe plus Nepal, Gambia and Taiwan). The cohort includes detailed phenotyping information which has been used by clinical working groups to rigorously categorise participants for example into definite viral and definite bacterial infection. The cohort is predominantly paediatric but includes vulnerable people such as pregnant women, neonates and the elderly. This biobank offers us an opportunity to generate bulk RNA-seq and blended WGS/WES data for a subset of patients to address some of the specific research questions our team are currently tackling.\nResearch questions:\n1. Is SRS group associated with more severe illness in this broader cohort which spans neonatal to elderly patients?\n2. How much does host genetics contribute to SRS group membership?\n3. Do we observe differential splicing between different infection types (or specific infections)?\n4. Can we identify examples of outlying gene expression, particularly in paediatric samples and link this to genetic variants?\n5. Can we use eQTL interactions to understand more about variation in the response to infection?","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008361","title":"HG_DIAMONDS_DNA","description":"The DIAMONDS (Diagnosis and Management of Febrile Illness using DNA Personalised Molecular Signature Diagnosis cohort was established to create a biobank of samples and clinical data collected from patients presenting with fever and diagnosed with diverse infectious and inflammatory conditions. To date, over 12,000 patients have been recruited across 15 countries (12 in Europe plus Nepal, Gambia and Taiwan). The cohort includes detailed phenotyping information which has been used by clinical working groups to rigorously categorise participants for example into definite viral and definite bacterial infection. The cohort is predominantly paediatric but includes vulnerable people such as pregnant women, neonates and the elderly. This biobank offers us an opportunity to generate bulk RNA-seq and blended WGS/WES data for a subset of patients to address some of the specific research questions our team are currently tackling.\nResearch questions:\n1. Is SRS group associated with more severe illness in this broader cohort which spans neonatal to elderly patients?\n2. How much does host genetics contribute to SRS group membership?\n3. Do we observe differential splicing between different infection types (or specific infections)?\n4. Can we identify examples of outlying gene expression, particularly in paediatric samples and link this to genetic variants?\n5. Can we use eQTL interactions to understand more about variation in the response to infection?\n","abstract":"The DIAMONDS (Diagnosis and Management of Febrile Illness using DNA Personalised Molecular Signature Diagnosis cohort was established to create a biobank of samples and clinical data collected from patients presenting with fever and diagnosed with diverse infectious and inflammatory conditions. To date, over 12,000 patients have been recruited across 15 countries (12 in Europe plus Nepal, Gambia and Taiwan). The cohort includes detailed phenotyping information which has been used by clinical working groups to rigorously categorise participants for example into definite viral and definite bacterial infection. The cohort is predominantly paediatric but includes vulnerable people such as pregnant women, neonates and the elderly. This biobank offers us an opportunity to generate bulk RNA-seq and blended WGS/WES data for a subset of patients to address some of the specific research questions our team are currently tackling.\nResearch questions:\n1. Is SRS group associated with more severe illness in this broader cohort which spans neonatal to elderly patients?\n2. How much does host genetics contribute to SRS group membership?\n3. Do we observe differential splicing between different infection types (or specific infections)?\n4. Can we identify examples of outlying gene expression, particularly in paediatric samples and link this to genetic variants?\n5. Can we use eQTL interactions to understand more about variation in the response to infection?\n","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008362","title":"Oesophageal_Adenocarcinoma_Organoid_Assemblies","description":"Genome assemblies of 5 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical resection of the tumour. All model derivations took place with the CGaP facility in Sanger. Composed of PacBio, and short read HiC data combined to generate accurate reference cancer genomes.","abstract":"There is complex interplay between underlying genetic sequence and epigenetic factors, however this interplay is still illusive. Massively reconstructed cancer genomes can be used in order to better understand this relationship. Five oesophageal adenocarcinoma organoids were be sequenced using long read sequencing technologies and were profiled for a range of epigenetic marks. Combination of genetic and epigenetic data  allows the thorough characterisation of reference cancer genomes and will provide novel insights into mechanisms of gene regulation","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008363","title":"LC-MS/MS-based proteomics study for the exploratory characterisation of immunohistologically-defined breast cancer subtypes.","description":"Background: Breast cancer classification is based on immunohistochemical (IHC) expression patterns, which are important for prognosis and predictive for treatment response. In this study, we analyzed the proteomic profiles of IHC-defined breast cancer.\nMethods: 117 formalin-fixed, paraffin-embedded tumor samples and 16 corresponding adjacent non-neoplastic tissues were analyzed using liquid chromatography – tandem mass spectrometry. DIA data analysis was conducted using DIA-NN using a predicted spectral library. Differential analysis was conducted using the LIMMA package.\nResults: Proteomic analysis revealed significant differences between tumor and adjacent non-neoplastic tissues as well as expression patterns partially aligning with IHC classification. Specifically, triple-negative breast cancer showed increased expression of proteins related to cell proliferation and immunity but reduced for some metabolic processes, while luminal A and B subtypes were each separated into two subclusters, one of which exhibited increased stromal protein expression in both cases.\nConclusions: We expanded upon the protein profiles of major breast cancer subtypes, confirming traditional IHC findings. The identification of distinct proteomic subgroups within the luminal A and luminal B subtypes suggests that proteomic analysis could provide a more detailed understanding of these cancers, potentially leading to new diagnostic or treatment strategies.\n","abstract":"Background: Breast cancer classification is based on immunohistochemical (IHC) expression patterns, which are important for prognosis and predictive for treatment response. In this study, we analyzed the proteomic profiles of IHC-defined breast cancer.\nMethods: 117 formalin-fixed, paraffin-embedded tumor samples and 16 corresponding adjacent non-neoplastic tissues were analyzed using liquid chromatography – tandem mass spectrometry. DIA data analysis was conducted using DIA-NN using a predicted spectral library. Differential analysis was conducted using the LIMMA package.\nResults: Proteomic analysis revealed significant differences between tumor and adjacent non-neoplastic tissues as well as expression patterns partially aligning with IHC classification. Specifically, triple-negative breast cancer showed increased expression of proteins related to cell proliferation and immunity but reduced for some metabolic processes, while luminal A and B subtypes were each separated into two subclusters, one of which exhibited increased stromal protein expression in both cases.\nConclusions: We expanded upon the protein profiles of major breast cancer subtypes, confirming traditional IHC findings. The identification of distinct proteomic subgroups within the luminal A and luminal B subtypes suggests that proteomic analysis could provide a more detailed understanding of these cancers, potentially leading to new diagnostic or treatment strategies.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008364","title":"Proteomic Characterization of sporadic clear cell renal cell carcinoma 2025","description":"Clear cell renal cell carcinoma (ccRCC) frequently develops a fibrotic pseudocapsule (PC) at the tumor boundary, yet its implications in the disease remain incompletely defined. We performed DIA-based proteomics on formalin-fixed paraffin-embedded (FFPE) specimens of sporadic ccRCC from 153 patients, comprising 142 tumor, 123 pseudocapsule (PC), and 121 non-malignant adjacent tissue (NAT) samples. The PC displayed a distinctive proteomic signature, characterized by matrix accumulation, enhanced remodeling, and ECM-cell signaling, consistent with a signaling-competent boundary and active growth factor sequestration, rather than a passive fibrotic barrier. Within the tumor, we observed canonical metabolic reprogramming with upregulated glycolysis and hypoxia markers and suppression of aerobic metabolism, accompanied by strong cell-cycle and pro-angiogenic signatures. Immune programs included increased antigen processing and presentation, together with elevated inflammasome and pyroptosis signatures. T-cell markers were enriched in the PC, indicating an immune-active boundary. Among tumors, we identified five distinct proteomic subtypes (C1–C5) spanning proliferative/mitotic, metabolic, immune/EMT/mTOR, and ECM phenotypes. Semi-specific peptide analysis indicated elevated endogenous proteolysis in the tumor and varied across clusters, with C1 and C5 showing the greatest proteolytic burden. Mechanotransduction features showed only modest PC elevation but were dominated by inter-patient variation. The present study defines a matrix-rich, signaling-active pseudocapsule and a classification of heterogeneous tumor subtypes in sporadic ccRCC. The framework provides a compartment-resolved, cluster-informed approach, and it highlights actionable axes of potential clinical relevance. ","abstract":"Clear cell renal cell carcinoma (ccRCC) frequently develops a fibrotic pseudocapsule (PC) at the tumor boundary, yet its implications in the disease remain incompletely defined. We performed DIA-based proteomics on formalin-fixed paraffin-embedded (FFPE) specimens of sporadic ccRCC from 153 patients, comprising 142 tumor, 123 pseudocapsule (PC), and 121 non-malignant adjacent tissue (NAT) samples. The PC displayed a distinctive proteomic signature, characterized by matrix accumulation, enhanced remodeling, and ECM-cell signaling, consistent with a signaling-competent boundary and active growth factor sequestration, rather than a passive fibrotic barrier. Within the tumor, we observed canonical metabolic reprogramming with upregulated glycolysis and hypoxia markers and suppression of aerobic metabolism, accompanied by strong cell-cycle and pro-angiogenic signatures. Immune programs included increased antigen processing and presentation, together with elevated inflammasome and pyroptosis signatures. T-cell markers were enriched in the PC, indicating an immune-active boundary. Among tumors, we identified five distinct proteomic subtypes (C1–C5) spanning proliferative/mitotic, metabolic, immune/EMT/mTOR, and ECM phenotypes. Semi-specific peptide analysis indicated elevated endogenous proteolysis in the tumor and varied across clusters, with C1 and C5 showing the greatest proteolytic burden. Mechanotransduction features showed only modest PC elevation but were dominated by inter-patient variation. The present study defines a matrix-rich, signaling-active pseudocapsule and a classification of heterogeneous tumor subtypes in sporadic ccRCC. The framework provides a compartment-resolved, cluster-informed approach, and it highlights actionable axes of potential clinical relevance. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008365","title":"Tumour_profiling_from_Danish_biliary_tract_cancer_patients_receiving_immune_checkpoint_inhibitors","description":"Bulk RNA-seq of tumour biopsies from the CheckPAC clinical trial","abstract":"As part of the CheckPAC trial (NCT02866383), our collaborators at Herlev Hospital (Denmark) randomised patients with advanced biliary tract cancer (BTC) to receive different regimens of immune checkpoint inhibitors (ICIs), with a subset of patients benefiting from this treatment. This project aims to perform bulk RNA-seq from baseline BTC biopsy specimens to identify host and microbial transcriptomic signatures correlating with response and stool microbial composition.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008366","title":"CG_Tongue_P_BW_RNA_Behjati_Managed","description":"Beckwith-Wiedemann syndrome (BWS) is a congenital disorder associated with overgrowth and predisposition to certain cancers, caused by abnormalities in the methylation of regulatory regions on chr11p. Patients often present with hemi-hypertrophy, i.e., overgrowth of certain body parts, such as the tongue, only on one side of their body. Tongue resection surgery is often done to improve patients’ life quality. In this study, we perform multimodal sequencing of resected tongues to compare the overgrown and non-overgrown sides to understand why the phenotype is seen only on one side of the body. By comparing the left and right side of the body, we can understand the lineage relationships of cells with alterations in chr11p methylation and the transcriptional consequences of those changes depending on the context (overgrown vs non-overgrown side).","abstract":"Beckwith-Wiedemann syndrome (BWS) is a congenital disorder associated with overgrowth and predisposition to certain cancers, caused by abnormalities in the methylation of regulatory regions on chr11p. Patients often present with hemi-hypertrophy, i.e., overgrowth of certain body parts, such as the tongue, only on one side of their body. Tongue resection surgery is often done to improve patients’ life quality. In this study, we perform multimodal sequencing of resected tongues to compare the overgrown and non-overgrown sides to understand why the phenotype is seen only on one side of the body. By comparing the left and right side of the body, we can understand the lineage relationships of cells with alterations in chr11p methylation and the transcriptional consequences of those changes depending on the context (overgrown vs non-overgrown side).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008367","title":"LiFTS_LCMB_WGS","description":"Profiling of mutational and clonal landscape of blood derived single cell colonies from patients with Li_fraumeni Syndrome ","abstract":"Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with high risks for a broad spectrum of cancers including early-onset cancers. The lifetime risks of cancer for women and men with  LFS are 90% and 70%, respectively, with 50% of cancers occur prior to age 40 years. \nLFS is associated with a germline pathogenic variant in TP53 gene, however the mechanism by which the mutation causes malignant transformation are still unknown. \nIn this study blood derived single cell colonies from LFS patients will be analysed through the LCMB pipeline and the data used to investigate the mutational and clonal profile and then build phylogenies of the hematopoetic tissues ","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008368","title":"CG_Tongue_P_BW_ATAC_Behjati_Managed","description":"Beckwith-Wiedemann syndrome (BWS) is a congenital disorder associated with overgrowth and predisposition to certain cancers, caused by abnormalities in the methylation of regulatory regions on chr11p. Patients often present with hemi-hypertrophy, i.e., overgrowth of certain body parts, such as the tongue, only on one side of their body. Tongue resection surgery is often done to improve patients’ life quality. In this study, we perform multimodal sequencing of resected tongues to compare the overgrown and non-overgrown sides to understand why the phenotype is seen only on one side of the body. By comparing the left and right side of the body, we can understand the lineage relationships of cells with alterations in chr11p methylation and the transcriptional consequences of those changes depending on the context (overgrown vs non-overgrown side).","abstract":"Beckwith-Wiedemann syndrome (BWS) is a congenital disorder associated with overgrowth and predisposition to certain cancers, caused by abnormalities in the methylation of regulatory regions on chr11p. Patients often present with hemi-hypertrophy, i.e., overgrowth of certain body parts, such as the tongue, only on one side of their body. Tongue resection surgery is often done to improve patients’ life quality. In this study, we perform multimodal sequencing of resected tongues to compare the overgrown and non-overgrown sides to understand why the phenotype is seen only on one side of the body. By comparing the left and right side of the body, we can understand the lineage relationships of cells with alterations in chr11p methylation and the transcriptional consequences of those changes depending on the context (overgrown vs non-overgrown side).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008369","title":"CRISPR_screens_in_primary_human_Tregs","description":"Regulatory T cells (Tregs) play a role in maintaining immune homeostasis by suppressing the pro-inflammatory activities of other immune cells, which is achieved through the expression of surface markers with suppressive functions. We will perform pooled CRISPR screens on Tregs isolated from blood of healthy donors using a targeted library to identify knockouts that either enhance or diminish the expression of these molecules on Tregs. The Tregs will be sorted by FACS based on their phenotypic profile and pooled CRISPR libraries will be generated by amplifying guide RNA using a 2 step PCR process. These findings will provide insights into the pathways governing Treg suppressive activity and how they can be modulated for the treatment of inflammatory diseases.","abstract":"Regulatory T cells (Tregs) play a crucial role in maintaining immune homeostasis by suppressing the pro-inflammatory activities of other immune cells. Recent research has shown that the heritability of inflammatory bowel disease (IBD) is enriched in Treg-specific enhancers, suggesting that impaired Treg function contributes to disease susceptibility. Understanding the genetic and molecular mechanisms that regulate Treg activity is therefore a promising avenue for identifying potential therapeutic targets for autoinflammatory conditions. We will conduct pooled CRISPR screens using a targeted library to identify gene knockouts that either enhance or diminish the expression of these molecules. These findings will provide critical insights into the pathways governing Treg suppressive activity and how they can be modulated to develop new treatments for IBD and other autoimmune diseases. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008370","title":"ONT_and_PacBio_long_read_sequencing","description":"Sequence samples using long-read technologies in order to verify the signal we found in single-cell derived colonies from the same individual can be retrieved in single molecules. We will generate both ONT and PacBio data in order to compare and contrast how the two methods perform. Lastly, we will develop novel computational methods to reconstruct phylogenetic trees from long-read sequencing data.","abstract":"Sequence samples using long-read technologies in order to verify the signal we found in single-cell derived colonies from the same individual can be retrieved in single molecules. We will generate both ONT and PacBio data in order to compare and contrast how the two methods perform. Lastly, we will develop novel computational methods to reconstruct phylogenetic trees from long-read sequencing data.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008371","title":"Neuroimmune_iPS_WGS","description":"Innate and adaptive immune responses play an important role in the genesis or progression of many neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Amyotrophic Lateral Sclerosis (ALS). Single cell and spatial transcriptomics of human brain samples have identified the presence of many different disease-specific microglial states and T cell infiltration; however, it is still unclear what the underlying cellular mechanisms are, at what stages in disease progression immune cells are protective or detrimental, whether there are shared mechanisms across diseases and how genetic predispositions affect these processes. The NeuroImmune Project aims to understand the signals or pathological features driving disease-associated microglial states, the underlying cellular mechanisms that define these states, and their downstream effects on other cell types including T cells, astrocytes and neurons. The project will employ large-scale spatial and single cell analysis of hiPSC models that have been matched to patient samples with similar polygenic risk scores (PRS) or causal mutations. The analysis will aim to identify cell signalling pathways, cell-cell interactions and downstream pathways that are involved within and across neurodegenerative disease which would be good targets for therapeutic intervention. \n\nWe are performing long read whole genome sequencing of the hiPSC lines to be used in this study (mainly from the IPMAR collection) to look for common, rare and structural variants that are associated with cellular phenotypes and to select genetically matched patient and hiPSC samples for comparison.\n\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"Innate and adaptive immune responses play an important role in the genesis or progression of many neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Amyotrophic Lateral Sclerosis (ALS). Single cell and spatial transcriptomics of human brain samples have identified the presence of many different disease-specific microglial states and T cell infiltration; however, it is still unclear what the underlying cellular mechanisms are, at what stages in disease progression immune cells are protective or detrimental, whether there are shared mechanisms across diseases and how genetic predispositions affect these processes. The NeuroImmune Project aims to understand the signals or pathological features driving disease-associated microglial states, the underlying cellular mechanisms that define these states, and their downstream effects on other cell types including T cells, astrocytes and neurons. The project will employ large-scale spatial and single cell analysis of hiPSC models that have been matched to patient samples with similar polygenic risk scores (PRS) or causal mutations. The analysis will aim to identify cell signalling pathways, cell-cell interactions and downstream pathways that are involved within and across neurodegenerative disease which would be good targets for therapeutic intervention.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008372","title":"Single_molecule_somatic_mutation_detection","description":"PacBio high fidelity (HiFi) sequencing produces accurate long-reads using the complementary information contained within the double-stranded DNA. We hope to use the HiFi reads for single molecule somatic mutation detection across different species in the Darwin Tree of Life Project. We selected BC-1 cell-line with APOBEC-based mutagenesis and HT-115 cell-line POLE-based mutagenesis that predominantly produces SBS2 and SBS10 mutational signature, respectively. The somatic mutations in these cell-lines will act as positive controls and will enable us to distinguish substitution errors in HiFi reads from real somatic mutations. We will also perform systematic comparison between duplex sequencing and HiFi sequencing and determine the sensitivity and specificity of each approaches for single molecule somatic mutation detection. ","abstract":"Using single molecule somatic mutation detection methods, we aim to determine the mutation rate, mutational signatures and biological processes underpinning the mutational signatures across the normal tissues of different species in the Darwin Tree of Life Project. ","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008373","title":"mRNAseq of CRISPRa/i perturbation of ZNF331, ZNF10 and ZNF184 on hiPSCs","description":"Gene expression was assayed in non-differentiated hiPSCs bearing a Doxycycline-inducible NGN2 expression casette (unused in this assay) as well as either a CRISPRa or a CRISPRi stable expression casette. Cells were infected with Lentiviruses coding for gRNAs against either ZNF331, ZNF10, ZNF184 or against LacZ (used as NT control) and collected after 7 days of infection and antibiotic-based selection. For each perturbation condition, two or three biological replicates bearing different gRNAs were collected. Total RNA was extracted from cultured cells using the RNeasy Mini kit (Qiagen). mRNA-seq libraries were prepared from each sample using the NEBNext Ultra II RNA Library Prep Kit for Illumina and sequenced on an Illumina Nextseq 2000 platform (Read configuration: 132 cycles Read 1, 6 cycles index 1).","abstract":"genetic modification design","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008374","title":"mRNAseq of CRISPRi perturbation of ZNF331, ZNF10 and ZNF184 coupled to KCl stimulation on 50DIV hiGNs-mAstrocytes co-culture","description":"Gene expression was assayed in 50 DIV hiGNs differentiated from Doxycycline-inducible NGN2 expression casette-containing hiPSCs, which also bore a CRISPRi stable expression casette and were infected with Lentiviruses coding for gRNAs against either ZNF331, ZNF10, ZNF184 or against LacZ (used as NT control). Cells were collected after an O/N D-AP5 and TTX silencing followed by 4h of 55 mM KCl treatment. Controls (\"Basal\" condition) were only silenced. For each treatment condition, two biological replicates bearing different gRNAs were collected. Total RNA was extracted from cultured cells using the RNeasy Mini kit (Qiagen). mRNA-seq libraries were prepared from each sample using the NEBNext Ultra II RNA Library Prep Kit for Illumina and sequenced on an Element Biosciences AVITI System (Avidite Base Chemistry, Element Biosciences) (Read configuration: 132 cycles Read 1, 6 cycles index 1).","abstract":"compound treatment design;time series design;genetic modification design","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008375","title":"Total RNAseq of KCl stimulation timecourse on 50DIV hiGNs-mAstrocytes co-culture","description":"Gene expression was assayed in 50 DIV hiGNs differentiated from Doxycycline-inducible NGN2 expression casette-containing hiPSCs. Cells were collected after an O/N D-AP5 and TTX silencing followed by either 1, 2, 4 or 8 h of 55 mM KCl treatment. Controls (\"Basal\" condition) were only silenced. For each treatment condition, two biological replicates were collected. Total RNA was extracted from cultured cells using the RNeasy Mini kit (Qiagen). Total RNA-seq libraries were prepared from each sample using the NEB Next Ultra II rRNA depletion followed by directional RNA library prep kit for Illumina and sequenced on an Element Biosciences AVITI System (Avidite Base Chemistry, Element Biosciences) using a High-Output 150 cycle Kit. (Read configuration: 84 cycles Read 1, 84 cycles Read 2, 8 cycles index 1, 8 cycles index 2).","abstract":"compound treatment design;time series design","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008376","title":"ChIP-tagmentation-seq against H3K9me3 of CRISPRi perturbation of ZNF331, ZNF10 and ZNF184 coupled to KCl stimulation on 50DIV hiGNs-mAstrocytes co-culture","description":"ChIP-tagmentation-seq H3K9me3 signal was assayed in 50 DIV hiGNs differentiated from Doxycycline-inducible NGN2 expression casette-containing hiPSCs, which also bore a CRISPRi stable expression casette and were infected with Lentiviruses coding for gRNAs against either ZNF331, ZNF10, ZNF184 or against LacZ (used as NT control). Cells were collected after an O/N D-AP5 and TTX silencing followed by 4 h of 55 mM KCl treatment. Controls (\"Basal\" condition) were only silenced. For each treatment condition, two biological replicates bearing different gRNAs were collected. Sequencing libraries were prepared using a protocol optimized from the original ChIP-tagmentation-seq protocol (Schmidl et al. 2015), and used to detect interaction between DNA and target histone modifications. Briefly, fresh cells were harvested and its nuclei were isolated, fixed in 1% PFA and snap-frozen. Fixed-frozen nuclei were then sonicated and incubated with antibody-bound protein A beads. Immunoprecipitated DNA was next decrosslinked, proteinase K-treated and purified. Sequencing libraries were prepared via incubation of the naked DNA with Tn5. Sequencing adaptor-bound DNA was next PCR-amplified and barcoded, and finally sequenced on an Element Biosciences AVITI System (Avidite Base Chemistry, Element Biosciences) (Read configuration: 84 cycles Read 1, 84 cycles Read 2, 8 cycles index 1, 8 cycles index 2).","abstract":"compound treatment design;time series design;genetic modification design","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008377","title":"C&T-seq against H3K27ac of CRISPRi perturbation of ZNF331, ZNF10 and ZNF184 coupled to KCl stimulation on 50 DIV hiGNs-mAstrocytes co-culture","description":"C&amp;T-seq H3K27ac signal was assayed in 50 DIV hiGNs differentiated from Doxycycline-inducible NGN2 expression casette-containing hiPSCs, which also bore a CRISPRi stable expression casette and were infected with Lentiviruses coding for gRNAs against either ZNF331, ZNF10, ZNF184 or against LacZ (used as NT control). Cells were collected after an O/N D-AP5 and TTX silencing followed by 4 h of 55 mM KCl treatment. Controls (\"Basal\" condition) were only silenced. For each treatment condition, two biological replicates bearing different gRNAs were collected. Sequencing libraries were prepared using a protocol optimized from the original C&amp;T-seq protocol (Kaya-Okur et al. 2020), and used to detect interaction between DNA and target histone modifications. Briefly, fresh cells were harvested, its nuclei were isolated and permeabilized, bound to concavalin magnetic beads and incubated with the antibody for the modification of interest. Samples were then incubated with pA-Tn5 to cut the DNA surrounding the bound antibody as well as to introduce sequencing adaptors. Purified DNA was next PCR-amplified and barcoded, and finally sequenced in an Illumina NextSeq 2000 platform (Read configuration: 61 cycles Read 1, 8 cycles index 1, 61 cycles Read 2, 8 cycles index 2).","abstract":"compound treatment design;time series design;genetic modification design","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008378","title":"C&T-seq against H3K27ac of KCl stimulation timecourse on 50DIV hiGNs-mAstrocytes co-culture","description":"C&amp;T-seq H3K27ac signal was assayed in 50 DIV hiGNs differentiated from Doxycycline-inducible NGN2 expression casette-containing hiPSCs. Cells were collected after an O/N D-AP5 and TTX silencing followed by either 1, 2, 4 or 8 h of 55 mM KCl treatment. Controls (\"Basal\" condition) were only silenced. For each treatment condition, two technical replicates were collected. Sequencing libraries were prepared using a protocol optimized from the original C&amp;T-seq protocol (Kaya-Okur et al. 2020), and used to detect intereaction between DNA and target histone modifications. Briefly, fresh cells were harvested, its nuclei were isolated and permeabilized, bound to concavalin magnetic beads and incubated with the antibody for the modification of interest or IgG as control. Samples were then incubated with pA-Tn5 to cut the DNA surrounding the bound antibody as well as to introduce sequencing adaptors. Purified DNA was next PCR-amplified and barcoded, and finally sequenced in an Illumina NextSeq 2000 platform (Read configuration: 61 cycles Read 1, 8 cycles index 1, 61 cycles Read 2, 8 cycles index 2).","abstract":"compound treatment design;time series design","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008379","title":"mRNAseq of KCl stimulation timecourse on 50DIV hiGNs-mAstrocytes co-culture","description":"Gene expression was assayed in 50 DIV hiGNs differentiated from Doxycycline-inducible NGN2 expression casette-containing hiPSCs. Cells were collected after an O/N D-AP5 and TTX silencing followed by either 1, 2, 4 or 8 h of 55 mM KCl treatment. Controls (\"Basal\" condition) were only silenced. For each treatment condition, two biological replicates were collected. Total RNA was extracted from cultured cells using the RNeasy Mini kit (Qiagen). mRNA-seq libraries were prepared from each sample in technical duplicates (yielding 4 samples per condition) using the NEBNext Ultra II RNA Library Prep Kit for Illumina and sequenced in an Illumina NextSeq 500 platform (Read configuration: 75 cycles Read 1, 6 cycles index 1).","abstract":"compound treatment design;time series design","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008380","title":"The Jackson Laboratory Genetically Diverse Human Induced Pluripotent Stem Cell (GeDi hiPSC) Resource","description":"The Jackson Laboratory (JAX) Genetically Diverse (GeDi) Human Induced Pluripotent Stem Cell (hiPSC) Resource aims to establish a publicly available panel of well-characterized male and female clonal hiPSC lines derived from genetically diverse, healthy individuals. Donor participation is based on informed consent permitting the distribution of both the cell lines and associated genomic and transcriptomic data for academic and commercial research use. The initial data release includes eight GeDi hiPSC lines with whole-genome sequencing, DNA methylation profiles, bulk RNA-seq from undifferentiated and differentiated cell types, and Infinium Global Diversity Array genotypes. Future releases will expand the number of lines and data types. By combining high-quality, consented cell lines with comprehensive molecular profiling, the JAX GeDi Resource enables studies of how human genetic background and sex-specific variation influence cellular phenotypes, differentiation potential, and pharmacological responses.","abstract":"The Jackson Laboratory (JAX) Genetically Diverse (GeDi) Human Induced Pluripotent Stem Cell (hiPSC) Resource aims to establish a publicly available panel of well-characterized male and female clonal hiPSC lines derived from genetically diverse, healthy individuals. Donor participation is based on informed consent permitting the distribution of both the cell lines and associated genomic and transcriptomic data for academic and commercial research use. The initial data release includes eight GeDi hiPSC lines with whole-genome sequencing, DNA methylation profiles, bulk RNA-seq from undifferentiated and differentiated cell types, and Infinium Global Diversity Array genotypes. Future releases will expand the number of lines and data types. By combining high-quality, consented cell lines with comprehensive molecular profiling, the JAX GeDi Resource enables studies of how human genetic background and sex-specific variation influence cellular phenotypes, differentiation potential, and pharmacological responses.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008381","title":"A plasma protein biomarker signature that differentiates acute rheumatic fever from related clinical presentations","description":"Acute Rheumatic Fever (ARF) is a systemic inflammatory condition triggered by Group A Streptococcus infection, with timely diagnosis critical to prevent Rheumatic Heart Disease. ARF pathogenesis is poorly understood and diagnosis is based on clinical criteria. Here, we compared ARF cases and well-defined controls from two Uganda cohorts. We identified a 5-protein signature that discriminates ARF patients from clinically-similar conditions (receiver operating characteristic-area under the curve (ROC-AUC)=1.0, n=18 definite ARF vs n=9 known alternate diagnosis; ROC-AUC=0.97, n=18 definite ARF vs n=13 unknown alternate diagnosis), which retained very good diagnostic value in a validation cohort (ROC-AUC=0.83 n=26 definite ARF vs n=13 unknown alternate diagnosis). Pathway analysis identified the epithelial-mesenchymal transition pathway as highly-associated with acute ARF, suggesting that tissue damage and repair is central to ARF pathogenesis. Our findings require further validation, yet highlight the potential for proteomics to identify clinically useful diagnostic biomarkers that would revolutionise ARF diagnosis and treatment. ","abstract":"Acute Rheumatic Fever (ARF) is a systemic inflammatory condition triggered by Group A Streptococcus infection, with timely diagnosis critical to prevent Rheumatic Heart Disease. ARF pathogenesis is poorly understood and diagnosis is based on clinical criteria. Here, we compared ARF cases and well-defined controls from two Uganda cohorts. We identified a 5-protein signature that discriminates ARF patients from clinically-similar conditions (receiver operating characteristic-area under the curve (ROC-AUC)=1.0, n=18 definite ARF vs n=9 known alternate diagnosis; ROC-AUC=0.97, n=18 definite ARF vs n=13 unknown alternate diagnosis), which retained very good diagnostic value in a validation cohort (ROC-AUC=0.83 n=26 definite ARF vs n=13 unknown alternate diagnosis). Pathway analysis identified the epithelial-mesenchymal transition pathway as highly-associated with acute ARF, suggesting that tissue damage and repair is central to ARF pathogenesis. Our findings require further validation, yet highlight the potential for proteomics to identify clinically useful diagnostic biomarkers that would revolutionise ARF diagnosis and treatment. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2025-12-18T03:06:49+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008382","title":"Stratton__Tracing_Historical_and_Anatomic_Trends_in_Colorectal_Microbial_Genotoxin_Exposure_","description":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. Here, we will study somatic mutations in benign colorectal epithelial tissue samples, including their matched normal tissues, to better understand mutational signatures, with a particular focus on microbial genotoxin-associated signatures and their spatial and temporal distribution.","abstract":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. Here, we will study somatic mutations in benign colorectal epithelial tissue samples, including their matched normal tissues, to better understand mutational signatures, with a particular focus on microbial genotoxin-associated signatures and their spatial and temporal distribution.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008383","title":"Single cell multiome profiling of non-diabetic pancreatic islets reveals variability in cell type-specific regulation associated with diabetes risk","description":null,"abstract":"The extent of normal variability in the gene regulatory programs of individual cell types in the pancreas has not been described. In this study we mapped gene regulation in pancreatic cell types using single cell multiomic (joint RNA-seq and ATAC-seq) profiling in 28 non-diabetic donors in combination with single cell data in 38 additional donors from several studies. We identified associations with age, sex, BMI, and HbA1c, where gene regulatory responses were highly cell type- and phenotype-specific. In beta cells, older age associated with increased apoptosis and stress responses, decreased damage repair, and altered circadian-dependent transcription factor activity, while BMI associated with altered insulin secretion, and sex with chromatin organization. We identified 12.3k loci where genetic variants were QTLs for cis regulatory element (cRE) accessibility, of which a third had cell type- or lineage-specific effects and disrupted distinct transcription factor motifs. Variants at 153 diabetes and glycemic trait loci showed cell type QTL association, of which 26 loci were colocalized. Target genes of colocalized QTLs revealed novel disease genes, including DYRK3 for type 1 diabetes which promoted beta cell survival in stem cell models. Our findings reveal regulatory programs of pancreatic cell types in non-diabetic individuals and identify programs and genes that modulate risk of diabetes.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008384","title":"BergenTB___Profiling_TB_tissue_from_the_pre_antibiotic_era_RNAseq","description":"The pathology of tuberculosis in the lung is highly diverse, ranging from localized granulomas with\nminimal tissue damage in primary infection to extensive caseous necrosis, cavitation, and fibrosis in\nadvanced or reactivated disease. This variability is influenced by factors such as host immune\nresponse, bacterial load, and coexisting conditions, resulting in different manifestations. In modern\ntissue samples, disease pathology is often shaped by antibiotic therapy targeting MTB. To better\nunderstand TB pathology in untreated cases, we have obtained lung tissue from TB patients during the\npre-antibiotic era (1931–1947) from the pathology archives at the Gades Institute of Pathology in\nBergen, Norway. These samples will be analyzed using spatial transcriptomics on the 10X Genomics\nVisium and Xenium platforms to examine both MTB and human gene expression. Additionally, DNA will\nbe extracted for M. tuberculosis-specific bait capture and next-generation sequencing. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","abstract":"The pathology of tuberculosis in the lung is highly diverse, ranging from localized granulomas with\nminimal tissue damage in primary infection to extensive caseous necrosis, cavitation, and fibrosis in\nadvanced or reactivated disease. This variability is influenced by factors such as host immune\nresponse, bacterial load, and coexisting conditions, resulting in different manifestations. In modern\ntissue samples, disease pathology is often shaped by antibiotic therapy targeting MTB. To better\nunderstand TB pathology in untreated cases, we have obtained lung tissue from TB patients during the\npre-antibiotic era (1931–1947) from the pathology archives at the Gades Institute of Pathology in\nBergen, Norway. These samples will be analyzed using spatial transcriptomics on the 10X Genomics\nVisium and Xenium platforms to examine both MTB and human gene expression. Additionally, DNA will\nbe extracted for M. tuberculosis-specific bait capture and next-generation sequencing.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008385","title":"   Characterization of Oncogenic Protein Isoforms as Targets for Myelodysplastic Syndromes","description":"Myelodysplastic syndromes (MDS) are hematopoietic malignancies characterized by cytopenia, aberrant maturation, and a high risk of progression to secondary acute myeloid leukemia (AML). While significant advances have been made in understanding the genetic landscape of MDS, the regulatory mechanisms underlying clonal evolution and disease progression remain poorly defined. One crucial but largely unexplored aspect of MDS pathogenesis is the role of alternative splicing in shaping the proteome. Dysregulated splicing has been linked to malignant transformation, yet its consequences at the protein level, particularly in MDS, remain elusive. This study, funded within the PHRT initiative of the ETH domain, aimed at systematically characterizing MDS-specific or onco-specific protein isoforms (OPIs) resulting from alternative splicing events, with a focus on their potential as therapeutic targets. Specifically, we investigated structural and functional protein isoforms that could serve as novel candidates for immune-based therapies (e.g., T cell or NK cell approaches) or small-molecule inhibitors. To achieve this, we employed a multi-omics approach, integrating genomics data from a targeted panel sequencing for somatic mutation profiling, RNA sequencing (RNA-seq) for transcriptome analysis, and data-independent acquisition mass spectrometry (DIA-SWATH-MS) to provide a quantitative proteomic snapshot. The study is based on viably biobanked bone marrow mononuclear cells from in total 94 patient samples, including five healthy bone marrow controls.","abstract":"Myelodysplastic syndromes (MDS) are hematopoietic malignancies characterized by cytopenia, aberrant maturation, and a high risk of progression to secondary acute myeloid leukemia (AML). While significant advances have been made in understanding the genetic landscape of MDS, the regulatory mechanisms underlying clonal evolution and disease progression remain poorly defined. One crucial but largely unexplored aspect of MDS pathogenesis is the role of alternative splicing in shaping the proteome. Dysregulated splicing has been linked to malignant transformation, yet its consequences at the protein level, particularly in MDS, remain elusive. This study, funded within the PHRT initiative of the ETH domain, aimed at systematically characterizing MDS-specific or onco-specific protein isoforms (OPIs) resulting from alternative splicing events, with a focus on their potential as therapeutic targets. Specifically, we investigated structural and functional protein isoforms that could serve as novel candidates for immune-based therapies (e.g., T cell or NK cell approaches) or small-molecule inhibitors. To achieve this, we employed a multi-omics approach, integrating genomics data from a targeted panel sequencing for somatic mutation profiling, RNA sequencing (RNA-seq) for transcriptome analysis, and data-independent acquisition mass spectrometry (DIA-SWATH-MS) to provide a quantitative proteomic snapshot. The study is based on viably biobanked bone marrow mononuclear cells from in total 94 patient samples, including five healthy bone marrow controls.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008386","title":"Changes_in_mutational_landscape_after_chemotherapy","description":"We are studying changes in the mutational landscape in blood, buccal cells and urine before and after chemotherapy using targeted nanoseq","abstract":"We are studying changes in the mutational landscape in blood, buccal cells and urine before and after chemotherapy using targeted nanoseq","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008387","title":"VIVO_Behjati_WellcomeCore_T_Nanoseq","description":"Whilst some genomic features of rhabdomyosarcoma are employed in diagnosis and risk stratification in current protocols, new genomic biomarker discovery has been frustrated by small study sample sizes, or necessary focus on a small number of genes/regions of interest. The VIVO biobank currently stores pathological samples from over 600 patients with RMS.  This study has coordinated high quality and detailed clinical annotation of these samples, facilitating the identification of a cohort of clinical outliers and matched controls. These will undergo extensive whole genomic and transcriptomic sequencing to identify novel risk biomarkers and further delineate the genomic landscape of RMS. ","abstract":"Whilst some genomic features of rhabdomyosarcoma are employed in diagnosis and risk stratification in current protocols, new genomic biomarker discovery has been frustrated by small study sample sizes, or necessary focus on a small number of genes/regions of interest. The VIVO biobank currently stores pathological samples from over 600 patients with RMS.  This study has coordinated high quality and detailed clinical annotation of these samples, facilitating the identification of a cohort of clinical outliers and matched controls. These will undergo extensive whole genomic and transcriptomic sequencing to identify novel risk biomarkers and further delineate the genomic landscape of RMS. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008388","title":"Pleuritis_pleural_aspirate_Targeted_NanoSeq","description":"Targeted NanoSeq of pleural aspirates of donors with evidence of pleuritis with and without exposure to asbestos.","abstract":"Investigation of the mutational landscape of pleural aspirates with and without exposure to asbestos.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008389","title":"Microarray raw data on Chronic Thromboembolic Pulmonary Hypertension (CTEPH) endothelial cells, and a healthy control patients group","description":"Microarray raw data on Chronic Thromboembolic Pulmonary Hypertension (CTEPH) endothelial cells, and a healthy control patients group","abstract":"Microarray raw data on Chronic Thromboembolic Pulmonary Hypertension (CTEPH) endothelial cells, and a healthy control patients group","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008390","title":"Genome-wide evidence for the local ancestry of the Agotes from Navarra Spain","description":"The Agotes are among the most enigmatic minority social groups in the Iberian Peninsula, historically subjected to long-standing social marginalization by their non-Agote neighbors. Nowadays, most Agotes live in the small town of Bozate, (Baztan Valley, Navarra, Spain), but their origins remain disputed, with different hypotheses. In this study, we generated genome-wide genotype data from 125 newly sampled individuals from Bozate, the Baztan Valley and Navarra (Spain). Autosomal, sex chromosomes and mitochondrial microarray data are included in the Genome_Data_Agotes dataset.\n\nThe dataset from the Agotes Project was presented in the following article:\nGenome-wide evidence for the local ancestry of the Agotes from Navarra, Spain\nAlicia Portela-Estevez, Alin P. Acuna-Alonzo, Cesar A. Fortes-Lima, Elsa de Cabo, Amaya Gorostiza, Maitane Tirapu de Goni, Araxi O. Urrutia, Georgios Athanasiadis, Antonio Gonzalez-Martin. iScience, 2026, volume 29, issue 9, page 117229.\nhttps://doi.org/10.1016/j.isci.2026.117229","abstract":"The Agotes are among the most enigmatic minority social groups in the Iberian Peninsula, historically subjected to long-standing social marginalization by their non-Agote neighbors. Nowadays, most Agotes live in the small town of Bozate, (Baztan Valley, Navarra, Spain), but their origins remain disputed, with different hypotheses. In this study, we generated genome-wide genotype data from 125 newly sampled individuals from Bozate, the Baztan Valley and Navarra (Spain). Autosomal, sex chromosomes and mitochondrial microarray data are included in the Genome_Data_Agotes dataset.\n\nThe dataset from the Agotes Project was presented in the following article:\nGenome-wide evidence for the local ancestry of the Agotes from Navarra, Spain\nAlicia Portela-Estevez, Alin P. Acuna-Alonzo, Cesar A. Fortes-Lima, Elsa de Cabo, Amaya Gorostiza, Maitane Tirapu de Goni, Araxi O. Urrutia, Georgios Athanasiadis, Antonio Gonzalez-Martin. iScience, 2026, volume 29, issue 9, page 117229.\nhttps://doi.org/10.1016/j.isci.2026.117229","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-02-06T01:32:42+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008391","title":"Population history and genomic diversity in Burkina Faso","description":"For this project, DNA samples from 254 unrelated healthy individuals were genotyped using the Illumina Infinium H3Africa Consortium array (2,271,503 SNPs; BeadChip type: H3Africa_2019_20037295_B1) at the SNP&amp;SEQ Technology Platform (NGI/SciLifeLab Genomics, Sweden).","abstract":"For this project, DNA samples from 254 unrelated healthy individuals were genotyped using the Illumina Infinium H3Africa Consortium array (2,271,503 SNPs; BeadChip type: H3Africa_2019_20037295_B1) at the SNP&amp;SEQ Technology Platform (NGI/SciLifeLab Genomics, Sweden).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008392","title":"Genome-wide genotype data of Sahelian populations","description":"We collected samples from 376 individuals encompassing 16 populations across various locations within the Sahel/Savannah belt. We generated genome-wide genotype data of 376 participants using the Illumina Infinium H3Africa Consortium array (BeadChip type: H3Africa_2019_20037295_B1).","abstract":"We collected samples from 376 individuals encompassing 16 populations across various locations within the Sahel/Savannah belt. We generated genome-wide genotype data of 376 participants using the Illumina Infinium H3Africa Consortium array (BeadChip type: H3Africa_2019_20037295_B1).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008393","title":"Genome-wide study of populations from Central Africa","description":"We generated genome-wide genotype data using the Illumina Infinium H3Africa Consortium array (BeadChip type: TBD).","abstract":"We generated genome-wide genotype data using the Illumina Infinium H3Africa Consortium array (BeadChip type: TBD).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008394","title":"French Caribbean Genomic study","description":"We generated genome-wide genotype data using the Illumina Global Diversity array (BeadChip type: TBD).","abstract":"We generated genome-wide genotype data using the Illumina Global Diversity array (BeadChip type: TBD).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008395","title":"Microarray raw data on Chronic Thromboembolic Pulmonary Hypertension (CTEPH) endothelial cells, and a healthy control patients group","description":"Microarray raw data on Chronic Thromboembolic Pulmonary Hypertension (CTEPH) endothelial cells, and a healthy control patients group","abstract":"Microarray raw data on Chronic Thromboembolic Pulmonary Hypertension (CTEPH) endothelial cells, and a healthy control patients group","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008396","title":"LCM_WES_chronic_liver_disease","description":"Whole exome sequencing of laser capture microdissected cell populations from donors with chronic liver disease, including steatotic liver disease, viral hepatitis and inherited disorders amongst others.\n","abstract":"Investigating the driver landscape across chronic liver disease, comparing histological correlate to clonal architecture.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008397","title":"Clonal Evolution of Pediatric Acute Myeloid Leukemia and Its Contribution to Disease Relapse","description":"This series of genomic and RNA-sequencing data aims to investigate genetic and phenotypic changes between diagnosis and relapse of pediatric acute myeloid leukemia.","abstract":"This series of genomic and RNA-sequencing data aims to investigate genetic and phenotypic changes between diagnosis and relapse of pediatric acute myeloid leukemia.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008398","title":"Reactivation of a TAL1 progenitor cell enhancer region by non-coding somatic variants in T-lineage acute lymphoblastic leukemia","description":"Aberrant activation of TAL1, a key oncogenic driver, defines a major subgroup that accounts for ~30% of the childhood T-lineage acute lymphoblastic leukemia (T-ALL). We and others have shown that somatic non-coding mutations within upstream and intronic cis-regulatory regions of TAL1 contribute to transformation by creating binding sites for MYB and other transcription factors. However, activation mechanism of mutations in downstream enhancer regions where open chromatin and enhancer activity were found in hematopoietic progenitor cells, remains less understood. Here, we investigated cis-regulatory mechanisms mediated by somatic mutations occurring in an intergenic region located 29 kilobase pairs downstream of the canonical TAL1 transcription initiation site, involving 6% of T-ALLs that express TAL1. Epigenetic profiling was performed on human T-ALL cells from patient-derived xenograft (PDX) mouse models representing two different types of variants detected in patient samples which are either complex indels resulting in de novo MYB transcription factor binding sites (TFBSs) or internal tandem duplications (ITDs) encompassing canonical MYB TFBSs. Chromatin immunoprecipitation (ChIP) revealed binding of TAL1 core regulatory circuit (CRC) transcription factors MYB, GATA3, RUNX1, resulting in enhancer activity mediated by sequences significantly enriched for the mutant allele. Strikingly, ChIP-seq peaks for the repressive H3K27me3 mark and the active H3K27ac mark co-existed but enriched for different haplotypes at TAL1 exon 4. This resulted in allele-specific transcription of the short TAL1 isoform initiated at exon 4, reminiscent of enhancer-promoter interaction in progenitor cells during normal development. Furthermore, TAL1 T-ALLs harboring such variants are enriched for a lineage representing an earlier stage of T-cell development with cooperative driver mutations in CCND3 and MYB. These findings indicate that cell lineage may constrain the selection for cis-regulatory non-coding variants leading to reactivation of enhancers active in progenitor cells but silenced in differentiated lineages during normal development.","abstract":"Aberrant activation of TAL1, a key oncogenic driver, defines a major subgroup that accounts for ~30% of the childhood T-lineage acute lymphoblastic leukemia (T-ALL). We and others have shown that somatic non-coding mutations within upstream and intronic cis-regulatory regions of TAL1 contribute to transformation by creating binding sites for MYB and other transcription factors. However, activation mechanism of mutations in downstream enhancer regions where open chromatin and enhancer activity were found in hematopoietic progenitor cells, remains less understood. Here, we investigated cis-regulatory mechanisms mediated by somatic mutations occurring in an intergenic region located 29 kilobase pairs downstream of the canonical TAL1 transcription initiation site, involving 6% of T-ALLs that express TAL1. Epigenetic profiling was performed on human T-ALL cells from patient-derived xenograft (PDX) mouse models representing two different types of variants detected in patient samples which are either complex indels resulting in de novo MYB transcription factor binding sites (TFBSs) or internal tandem duplications (ITDs) encompassing canonical MYB TFBSs. Chromatin immunoprecipitation (ChIP) revealed binding of TAL1 core regulatory circuit (CRC) transcription factors MYB, GATA3, RUNX1, resulting in enhancer activity mediated by sequences significantly enriched for the mutant allele. Strikingly, ChIP-seq peaks for the repressive H3K27me3 mark and the active H3K27ac mark co-existed but enriched for different haplotypes at TAL1 exon 4. This resulted in allele-specific transcription of the short TAL1 isoform initiated at exon 4, reminiscent of enhancer-promoter interaction in progenitor cells during normal development. Furthermore, TAL1 T-ALLs harboring such variants are enriched for a lineage representing an earlier stage of T-cell development with cooperative driver mutations in CCND3 and MYB. These findings indicate that cell lineage may constrain the selection for cis-regulatory non-coding variants leading to reactivation of enhancers active in progenitor cells but silenced in differentiated lineages during normal development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008399","title":"PanCancer study","description":null,"abstract":"PanCancer study","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008400","title":"Spatial-temporal MPNST evolution - WGS","description":"Understanding the spatial and temporal dynamics of tumour evolution is crucial for determining the drivers of cancer progression. Here, we comprehensively profile a primary malignant peripheral nerve sheath tumour (MPNST) and its recurrence with a multi-omic and spatial approach at single-cell resolution. Leveraging the extensive heterogeneity in copy number aberrations (CNAs) as a native barcoding system, we fully resolve the evolutionary tree of this tumour revealing multi-furcations suggestive of ongoing chromosomal instability. We show gene dosage effects contribute to phenotypic diversity and are predominantly linear. Using laser capture microdissection, we performed spatial lineage tracing in a human tumour, elucidating the relationship between local expansions and interactions between tumour cells and the microenvironment.","abstract":"Understanding the spatial and temporal dynamics of tumour evolution is crucial for determining the drivers of cancer progression. Here, we comprehensively profile a primary malignant peripheral nerve sheath tumour (MPNST) and its recurrence with a multi-omic and spatial approach at single-cell resolution. Leveraging the extensive heterogeneity in copy number aberrations (CNAs) as a native barcoding system, we fully resolve the evolutionary tree of this tumour revealing multi-furcations suggestive of ongoing chromosomal instability. We show gene dosage effects contribute to phenotypic diversity and are predominantly linear. Using laser capture microdissection, we performed spatial lineage tracing in a human tumour, elucidating the relationship between local expansions and interactions between tumour cells and the microenvironment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008401","title":"CG_Reproductive_A__DM_Site_1_DNA_LEAP_MVS_Managed","description":"LEAP-MVS_DM_Site1 - Understanding the heterogeneity of reproduction related tissues by multi-level analyses and organoid and cell line derivation (genomic data)","abstract":"LEAP-MVS_DM_Site1 - Understanding the heterogeneity of reproduction related tissues by multi-level analyses and organoid and cell line derivation (DNA Study)","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008402","title":"CG_A_CRC_DNA_OTAR_3092_Managed","description":"Whole Genome sequencing to aid identification of cell populations composing CRC.","abstract":"\"Single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (STx) offer an unprecedented opportunity to identify the cell populations composing CRC and to map in great detail how transcriptomic states change in spatial cell-to-cell interactions of immune and tumour cells, and also between cytolytic and regulatory immune cell types. Furthermore, STx technologies offer the possibility to examine distribution of different cancer clones (2) in CRC and their interactions with diverse immune cells. This will provide vital data about the clonal structure of CRC in response to immunogenic control and a unique opportunity to evaluate the performance and interaction of putative targets within different CRC clones.\n\"","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008403","title":"Taste Receptor Gene Variants: Body Mass Index (BMI) and Longevity","description":"We evaluated differences in genotype and allele frequencies at the TAS1R2, TAS1R3, TAS2R38, and CD36 single-nucleotide polymorphisms (SNPs) and their associations with BMI and sex in two genetically and environmentally distinct populations: a cohort of near centenarian participants and a control cohort.","abstract":"We evaluated differences in genotype and allele frequencies at the TAS1R2, TAS1R3, TAS2R38, and CD36 single-nucleotide polymorphisms (SNPs) and their associations with BMI and sex in two genetically and environmentally distinct populations: a cohort of near centenarian participants and a control cohort.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-02-18T07:41:09+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008404","title":"Transcriptional and translational alterations induced by BET protein inhibition and its combination with Omaveloxolone in acute myeloid leukemia","description":"The inhibition of bromodomain and extra-terminal domain (BET) protein family achieved promising preclinical results as epigenetic therapy in acute myeloid leukemia (AML).  However, clinical data showed a limited activity of bromodomain inhibitor (BETi) as single agent. We aimed to investigate the role of hypoxia in the response of AML cells to BET inhibition in order to identify a novel therapeutic combination targeting leukemia stem-progenitor cells (LSPCs) in their niche.\nBETi maintained an anti-proliferative and pro-apoptotic activity at low oxygen concentration by modulating the leukemic transcriptional, translational and metabolic programs towards reduced ribosome biogenesis, altered polyamine metabolism and activation of a TNF- via NF-B signature at translational level, especially in hypoxic conditions. Accordingly, Omaveloxolone, a clinical-stage NF-B inhibitor and NFR2 activator approved for Friedreich’s ataxia, significantly enhanced the efficacy of BETi against AML cell lines in hypoxia and normoxia by reducing cell viability and enhancing apoptosis. At molecular level, the drug combination converged to the downregulation of MYC, the DNA replication and oxidative phosphorylation signatures while forcing the expression of antioxidant genes.\nOverall, the combination of BETi and Oma disrupts key metabolic and transcriptional programs essential to AML cell survival and LSPC maintenance in the hypoxic microenvironment.","abstract":"The inhibition of bromodomain and extra-terminal domain (BET) protein family achieved promising preclinical results as epigenetic therapy in acute myeloid leukemia (AML).  However, clinical data showed a limited activity of bromodomain inhibitor (BETi) as single agent. We aimed to investigate the role of hypoxia in the response of AML cells to BET inhibition in order to identify a novel therapeutic combination targeting leukemia stem-progenitor cells (LSPCs) in their niche.\nBETi maintained an anti-proliferative and pro-apoptotic activity at low oxygen concentration by modulating the leukemic transcriptional, translational and metabolic programs towards reduced ribosome biogenesis, altered polyamine metabolism and activation of a TNF- via NF-B signature at translational level, especially in hypoxic conditions. Accordingly, Omaveloxolone, a clinical-stage NF-B inhibitor and NFR2 activator approved for Friedreich’s ataxia, significantly enhanced the efficacy of BETi against AML cell lines in hypoxia and normoxia by reducing cell viability and enhancing apoptosis. At molecular level, the drug combination converged to the downregulation of MYC, the DNA replication and oxidative phosphorylation signatures while forcing the expression of antioxidant genes.\nOverall, the combination of BETi and Oma disrupts key metabolic and transcriptional programs essential to AML cell survival and LSPC maintenance in the hypoxic microenvironment.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-02-19T09:08:58+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008405","title":"Pan-cancer MSI and Lynch syndrome ","description":"This study comprises genome-wide SNP genotyping data generated from 24 human samples using the Illumina Global Screening Array (GSA) platform. Genomic DNA was extracted from peripheral blood samples and processed according to the manufacturer’s protocol. Genotyping was performed using the Infinium assay, producing raw intensity data in IDAT format.","abstract":"This study comprises genome-wide SNP genotyping data generated from 24 human samples using the Illumina Global Screening Array (GSA) platform. Genomic DNA was extracted from peripheral blood samples and processed according to the manufacturer’s protocol. Genotyping was performed using the Infinium assay, producing raw intensity data in IDAT format.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-02-20T08:24:05+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008406","title":"CG_NF1_Cambridge_Behjati_WellcomeCore_Spatial","description":"We have shown that histologically normal tissues from patients with neurofibromatosis exhibit frequent second hits that inactivate the wild-type NF1 allele (work under review). Inactivation of both copies of NF1, therefore, is not sufficient to transform a tissue to malignancy. Previous studies, however, have found the inactivation of both copies of NF1 to be the only discernible driver events in certain low grade tumours. This raises the question, therefore, as to why two hits sometimes transform a cell to a low grade tumour and sometimes do not. We hope to resolve this through a multiomic study that compares histologically normal cells with two NF1 hits with tumours with two NF1 hits.","abstract":"We have shown that histologically normal tissues from patients with neurofibromatosis exhibit frequent second hits that inactivate the wild-type NF1 allele (work under review). Inactivation of both copies of NF1, therefore, is not sufficient to transform a tissue to malignancy. Previous studies, however, have found the inactivation of both copies of NF1 to be the only discernible driver events in certain low grade tumours. This raises the question, therefore, as to why two hits sometimes transform a cell to a low grade tumour and sometimes do not. We hope to resolve this through a multiomic study that compares histologically normal cells with two NF1 hits with tumours with two NF1 hits.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008407","title":"Somatic mutations reveal the global spread trajectory and microevolution of Cavendish bananas","description":"Somatic mutations reveal the global spread trajectory and microevolution of Cavendish bananas","abstract":"Somatic mutations reveal the global spread trajectory and microevolution of Cavendish bananas","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008408","title":"Brazilian biorepository to support genome-wide association studies of colorectal, breast, and cervical cancer","description":"This study established a large-scale Brazilian biorepository to support cancer GWAS, replication studies, and polygenic risk score (PRS) evaluation for colorectal, breast, and cervical cancers. 4,062 participants have been enrolled, including cancer cases and cancer-free controls. Genotyping was performed in 2,844 participants using the Axiom 850K PMDA Array. Genetic ancestry inference confirmed Brazil’s highly admixed genetic background, with predominant European, followed by African, Native American, and Asian contributions. This biorepository provides a scalable resource to enable replication of genetic associations, assess the transferability of polygenic risk scores, and advance precision medicine in underrepresented populations.","abstract":"This study established a large-scale Brazilian biorepository to support cancer GWAS, replication studies, and polygenic risk score (PRS) evaluation for colorectal, breast, and cervical cancers. 4,062 participants have been enrolled, including cancer cases and cancer-free controls. Genotyping was performed in 2,844 participants using the Axiom 850K PMDA Array. Genetic ancestry inference confirmed Brazil’s highly admixed genetic background, with predominant European, followed by African, Native American, and Asian contributions. This biorepository provides a scalable resource to enable replication of genetic associations, assess the transferability of polygenic risk scores, and advance precision medicine in underrepresented populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-02-23T15:22:50+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008409","title":"Epigenetic ageing during the COVID-19 pandemic: global age acceleration, independent of SARS-CoV-2 infection","description":null,"abstract":"Introduction: The COVID-19 pandemic had profound effects for both infected and uninfected individuals. We aimed to identify acute and chronic epigenetic alterations from SARS-CoV-2 infection and/or lockdown measures. Methods: Both infected and uninfected participants from the TwinsUK cohort (n = 139) provided longitudinal whole-blood samples (Spring 2020, Spring 2021). Cross-sectional and longitudinal DNA methylome [DNAm] changes, including epigenetic ageing clocks, were assessed, and EWAS (Epigenome-Wide Association Studies) were performed. Changes in epigenetic ageing clocks were compared with longitudinal samples from an independent pre-pandemic cohort (n = 35, Nurses’ Health Study II cohort), assessed similarly. Results: Irrespective of SARS-CoV-2 infection, all individuals exhibited accelerated ageing from 2020 to 2021 (GrimAge clock age acceleration: p-value = 0.002, β = 0.99). In contrast, epigenetic data from paired samples from a separate pre-pandemic cohort, over a similar time period and assessed similarly, did not exhibit GrimAge acceleration. Epigenetic ageing did not differ between infected and uninfected individuals, or between recent and distant SARS-CoV-2 infection. Lastly, EWAS identified several putative changes in DNAm associated with recent, and distant, SARS-CoV-2 infection. Conclusions: Our longitudinal results suggest that the pandemic accelerated epigenetic ageing rates, irrespective of recent or distant SARS-CoV-2 infection.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008410","title":"Whole_Genome_Sequencing_PTALib__Healthy_","description":"The mutational landscape oh haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA (primary template-directed amplification).\nSamples have been sourced from CSCI.","abstract":"The mutational landscape oh haematopoietic cells will be characterized by WGS following amplification of DNA and preparation of libraries by PTA (primary template-directed amplification).\nSamples have been sourced from CSCI.\n","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008411","title":"PTA_Atrandi_Development","description":"Research and development project investigating the compatibility between Atrandi encapsulation and PTA library preparation.","abstract":"Research and development project investigating the compatibility between Atrandi encapsulation and PTA library preparation from the blood.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008412","title":"Profiling_gut_tissue_in_pre_term_infants__to_better_understand_early_life_gut_development_","description":"This study aims to profile gut tissue of infants. To that end, we will generate WGS data of leftover intestinal tissue collected during resection surgeries, which will enable a better understanding of early life gut development.","abstract":"The gastrointestinal (GI) tract performs diverse roles related to digestion, barrier function, immune regulation, and the absorption of nutrients. As a result, understanding its development and maturation is important for ensuring proper health and growth throughout the lifespan. While we have previously generated data characterizing fetal, pediatric, and adult intestinal development, we aim to further expand this dataset with samples from preterm and neonatal gut. This data will be critical in evaluating the possibility of multiple developmental gastrointestinal conditions","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008413","title":"CG_Skin_A_CTCL_RNA_Haniffa_Managed","description":"This project aims to define, profile and investigate the landscape of CTCL disease progression and treatment resistance using a variety of single-cell and single-nuclei omics sequencing methods (e.g. multiome sequencing and proteomics), whole genome sequencing, and spatial transcriptomics and proteomics (e.g. Visium, Xenium and high-plex protein expression).","abstract":"Cutaneous T cell lymphoma (CTCL) is a rare type of non-Hodgkin lymphoma that affects the skin and can present with varying prognoses. Despite recent advances in the understanding of the malignant T cells involved in CTCL, the tumour microenvironment (TME) and its impact on disease progression and therapy resistance remain largely unknown. \n\nThis project aims to define, profile and investigate the landscape of CTCL disease progression and treatment resistance using a variety of single-cell and single-nuclei omics sequencing methods (e.g. multiome sequencing and proteomics), whole genome sequencing, and spatial transcriptomics and proteomics (e.g. Visium, Xenium and high-plex protein expression).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008414","title":"Array-based DNA methylation analysis in blood from patients with Snijders Blok–Campeau syndrome (CHD3)","description":" DNA methylation array data generated using the Illumina Infinium MethylationEPIC BeadChip (v1.0 and v2.0) from whole-blood DNA of patients with Snijders Blok–Campeau syndrome (ORPHA:599082). Raw IDAT files were generated to identify differentially methylated regions in typical and atypical patients. ","abstract":" DNA methylation arrays from Illumina (EPICv1 and EPICv2) on CHD3-related developmental delay-speech delay-intellectual disability-abnormalities of vision-facial dysmorphism syndrome patients (Snijders Blok-Campeau syndrome) ","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-03-06T12:15:24+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008415","title":"DERMATLAS__Hidradenoma_WES","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are hidradenomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are hidradenomas.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008416","title":"DERMATLAS__Hidradenoma_RNAseq","description":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are hidradenomas.","abstract":"Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.  Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible\n       For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.\n       The cases in this cohort are hidradenomas.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008417","title":"Genome-wide genotyping and methylation data from Understanding Society","description":"Genome-wide genotyping and methylation data from Understanding Society. Please visit https://www.understandingsociety.ac.uk/ for further information.","abstract":"Genome-wide genotyping and methylation data from Understanding Society. Please visit https://www.understandingsociety.ac.uk/ for further information.","study_type":"Other","pubmed_ids":[28887542,41781971],"external_links":null,"is_released":true,"released_date":"2026-03-12T15:33:22+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008418","title":"Test importer Study","description":"The abstract is being edited on the WEBIN as a test.","abstract":"The abstract is being edited on the WEBIN as a test.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008419","title":"Dynamic APOBEC3A-associated mutagenesis shapes the genomic landscape of ETV6::RUNX1-positive B-cell precursor acute lymphoblastic leukemia","description":"Recent studies have shown that high APOBEC activity is associated with increased therapy evasion in adult cancer. However, APOBEC mutagenesis in pediatric cancer has not been thoroughly characterized. In this study, we determined the prevalence and molecular characteristics of APOBEC mutagenesis in pediatric BCP-ALL using whole genome sequencing, bulk RNA sequencing and single cell RNA sequencing. We show that APOBEC mutagenesis s intrinsic to ETV6::RUNX1-positive samples and can drive clonal heterogeneity through subclonal activity.","abstract":"Recent studies have shown that high APOBEC activity is associated with increased therapy evasion in adult cancer. However, APOBEC mutagenesis in pediatric cancer has not been thoroughly characterized. In this study, we determined the prevalence and molecular characteristics of APOBEC mutagenesis in pediatric BCP-ALL using whole genome sequencing, bulk RNA sequencing and single cell RNA sequencing. We show that APOBEC mutagenesis s intrinsic to ETV6::RUNX1-positive samples and can drive clonal heterogeneity through subclonal activity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-03-20T07:24:54+01:00","is_deprecated":false},
{"accession_id":"EGAS00001008420","title":"CG_Skin_A_DERMATLAS_SebT_DNA_Haniffa_Managed","description":"This project aims to study the genetics of over 70 skin cancers to better understand the disease and improve diagnosis, treatment, and patient care.","abstract":"Aim to understand the genetics and genomics of over 70 different skin cancers to improve clinical practice, patient management and targeted therapies. This project wil generate single cell and spatial transcriptomic data to map the molecular landscape of these skin tumours to improve our understanding of disease. This dataset will also provide a foundational resource to understand the finer differences between tumour types and also in non-metastatic vs metastatic disease.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008421","title":"CG_Skin_A_DERMATLAS_Hair_Follicle__DNA_Haniffa_Managed","description":"This project aims to study the genetics of over 70 skin cancers to better understand the disease and improve diagnosis, treatment, and patient care.","abstract":"Aim to understand the genetics and genomics of over 70 different skin cancers to improve clinical practice, patient management and targeted therapies. This project wil generate single cell and spatial transcriptomic data to map the molecular landscape of these skin tumours to improve our understanding of disease. This dataset will also provide a foundational resource to understand the finer differences between tumour types and also in non-metastatic vs metastatic disease.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008422","title":"CG_Skin_A_DERMATLAS_Vascular_DNA_Haniffa_Managed","description":"This project aims to study the genetics of over 70 skin cancers to better understand the disease and improve diagnosis, treatment, and patient care.","abstract":"Aim to understand the genetics and genomics of over 70 different skin cancers to improve clinical practice, patient management and targeted therapies. This project wil generate single cell and spatial transcriptomic data to map the molecular landscape of these skin tumours to improve our understanding of disease. This dataset will also provide a foundational resource to understand the finer differences between tumour types and also in non-metastatic vs metastatic disease.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008423","title":"ITM Resistance to Immune Checkpoint","description":"The development of in-transit metastases of melanoma (ITM) presents a distinct clinical challenge due to their potential for dissemination, propensity for recurrence, and the formation of latent lesions. While immune checkpoint blockade (ICB) has significantly improved melanoma outcomes, resistance emerges in nearly half of treated patients, with the underlying mechanisms, particularly in ITM, remaining poorly understood. The study of ITM provides a unique model for investigating the evolving cellular mechanisms driving metastatic progression and therapeutic resistance. Here, we apply single cell multiomics on ITM biopsies from patients that received anti-PD-1 monotherapy or combination anti-PD-1+CTLA-4 therapies. Our analysis revealed a tumor microenvironment dominated by melanocytes, with limited immune and stromal cell infiltration. Within this cohort, genetic heterogeneity and dedifferentiation within the melanocyte compartment were associated with ICB resistance and disease progression. In contrast, T cell clonal expansion and clone sharing among specific tissue-resident memory T cell subsets was associated with ICB response. Integration of multiomic data using a random forest machine learning analysis highlighted the association of cell type composition with treatment response, above clinical, pathological or genomic features. Our findings provide the first multiomic characterization of ITM in the context of ICB, underscoring the critical role of genomic and cellular heterogeneity in ICB response, resistance, and disease progression.","abstract":"The development of in-transit metastases of melanoma (ITM) presents a distinct clinical challenge due to their potential for dissemination, propensity for recurrence, and the formation of latent lesions. While immune checkpoint blockade (ICB) has significantly improved melanoma outcomes, resistance emerges in nearly half of treated patients, with the underlying mechanisms, particularly in ITM, remaining poorly understood. The study of ITM provides a unique model for investigating the evolving cellular mechanisms driving metastatic progression and therapeutic resistance. Here, we apply single cell multiomics on ITM biopsies from patients that received anti-PD-1 monotherapy or combination anti-PD-1+CTLA-4 therapies. Our analysis revealed a tumor microenvironment dominated by melanocytes, with limited immune and stromal cell infiltration. Within this cohort, genetic heterogeneity and dedifferentiation within the melanocyte compartment were associated with ICB resistance and disease progression. In contrast, T cell clonal expansion and clone sharing among specific tissue-resident memory T cell subsets was associated with ICB response. Integration of multiomic data using a random forest machine learning analysis highlighted the association of cell type composition with treatment response, above clinical, pathological or genomic features. Our findings provide the first multiomic characterization of ITM in the context of ICB, underscoring the critical role of genomic and cellular heterogeneity in ICB response, resistance, and disease progression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008424","title":"CG_Skin_Cell_Line_HipSci_Haniffa_CRISPR_iPSC_SkOs_RNA_RNA_Haniffa_Managed","description":"Conducting a pooled CRISPR KO screen during SkO development to identify the master regulator genes required for development of every skin cell lineage present within the SkOs.","abstract":"Conducting a pooled CRISPR KO screen during SkO development to identify the master regulator genes required for development of every skin cell lineage present within the SkOs.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008425","title":"Immunogenetic_landscape_of_individuals_with_rare_cancers_WGS","description":"Identify somatic mutations in immune cell subsets from TP53 and PTEN carriers of pathogenic germline mutations and highly predisposed to develop cancer.","abstract":"Li-Fraumeni Syndrome (LFS) and PTEN Hamartomous Tumor Syndrome (PHTS) are rare cancers predisposition syndromes caused by pathogenic germline variations in the two well-known tumor suppressor genes, TP53 and PTEN, respectively. Both syndromes are associated with a high, lifelong risk of a broad spectrum of cancers in LFS and PHTS individuals. The impact of mutated P53 and PTEN in immune surveillance and tumour progression has been observed in human and mouse models. While recent studies have highlighted a well-established link between immune dysregulation and an elevated risk of cancer, primarily due to the failure of immune surveillance, very few studies have shed light on our understanding of the impact of the loss-of-function in PTEN and p53, the impairment of the immune response in LFS and PHTS individuals, and their role in the development of malignancy. We have previously optimised a multicolour panel to phenotype and sort immune cell populations by using spectrum flow cytometry in those individuals.  This proposal aims to draw the immune landscape from the blood compartment and identify the molecular signatures of six key immune cell populations (CD4+ T naïve, CD4+ T memory, CD8+ T naïve, CD8+ T memory, Tregs and B cells). We will collect blood samples of LFS, PHTS and healthy individuals, ten from each group. Phenotyping immune cells with our panel and identification of immune dysregulation signatures of sorted cells through full transcriptomic. Quantification of somatic mutational burden and signatures will be performed using a high sensitivity and low error rate duplex sequencing method (NanoSeq). Plasma cytokine levels and secreted forms of p53 and PTEN will be quantified through Olink, a high-throughput and sensitive technique. Tackling the cellular and molecular functions of these important genes and their regulation of the immune system in highly predisposed individuals with cancer recurrence, will bring improved understanding of the relationship of the immune response and cancer development. These insights will provide invaluable information that could guide the risk stratification strategies, early intervention, provide putative immunomarkers of cancer susceptibility and identify putative targets for novel immunotherapeutic development.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008426","title":"Immunogenetic_landscape_of_individuals_with_rare_cancers_Targeted_nanoseq","description":"Identify somatic mutations in immune cell subsets from TP53 and PTEN carriers of pathogenic germline mutations and highly predisposed to develop cancer.","abstract":"Li-Fraumeni Syndrome (LFS) and PTEN Hamartomous Tumor Syndrome (PHTS) are rare cancers predisposition syndromes caused by pathogenic germline variations in the two well-known tumor suppressor genes, TP53 and PTEN, respectively. Both syndromes are associated with a high, lifelong risk of a broad spectrum of cancers in LFS and PHTS individuals. The impact of mutated P53 and PTEN in immune surveillance and tumour progression has been observed in human and mouse models. While recent studies have highlighted a well-established link between immune dysregulation and an elevated risk of cancer, primarily due to the failure of immune surveillance, very few studies have shed light on our understanding of the impact of the loss-of-function in PTEN and p53, the impairment of the immune response in LFS and PHTS individuals, and their role in the development of malignancy. We have previously optimised a multicolour panel to phenotype and sort immune cell populations by using spectrum flow cytometry in those individuals.  This proposal aims to draw the immune landscape from the blood compartment and identify the molecular signatures of six key immune cell populations (CD4+ T naïve, CD4+ T memory, CD8+ T naïve, CD8+ T memory, Tregs and B cells). We will collect blood samples of LFS, PHTS and healthy individuals, ten from each group. Phenotyping immune cells with our panel and identification of immune dysregulation signatures of sorted cells through full transcriptomic. Quantification of somatic mutational burden and signatures will be performed using a high sensitivity and low error rate duplex sequencing method (NanoSeq). Plasma cytokine levels and secreted forms of p53 and PTEN will be quantified through Olink, a high-throughput and sensitive technique. Tackling the cellular and molecular functions of these important genes and their regulation of the immune system in highly predisposed individuals with cancer recurrence, will bring improved understanding of the relationship of the immune response and cancer development. These insights will provide invaluable information that could guide the risk stratification strategies, early intervention, provide putative immunomarkers of cancer susceptibility and identify putative targets for novel immunotherapeutic development.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008427","title":"HCA_Immune_Adult_Haniffa_RNA_Managed_Access","description":"TBC\n","abstract":"tbc","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008428","title":"HCA_Immune_Adult_Vento_RNA_Managed_Access","description":"A cell atlas of primary immunodeficiencies","abstract":"A cell atlas of primary immunodeficiencies","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-04-02T13:45:14+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008429","title":"HCA_Endometrium_Vento_RNA","description":"HCA Endometrium Vento RNA\n","abstract":"The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. This study includes single cell and organoid derived endometrium data.\n","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008430","title":"Methylation changes study on ayahuasca healthy users ","description":"Psychedelic use has been shown to improve human mental health and well-being for periods\nexceeding six months, and is a major area of interest in psychiatry and neuroscience. While little\nis known about the mechanisms of action of psychedelics, these improvements may be\nmediated by epigenetic processes. However, most preclinical assays have focused on acute or\npost-acute effects in animal models and cell cultures, and little is known about the specific\nepigenetic changes in human healthy volunteers. Here, we conducted a case-control study to\nevaluate the impact of ayahuasca - a classic serotonergic psychedelic containing N,N-\ndimethyltryptamine (DMT) - on the saliva methylome of ayahuasca users, whose time since self-\nadministration ranged from &amp;lt;1 week to 6 months, compared with a matched control group. DNA\nmethylation levels were quantified using the Infinium MethylationEPIC v2.0 BeadChips\n(Illumina). We observed significant differential methylation between the two groups at 494 CpG\nsites (DMPs) and a long-term effect of these methylation changes. DMPs functional analysis\nrevealed enrichment for terms related to immunity, angiogenesis and regulating cell cycle.\nDifferentially methylated region (DMR) analysis identified 57 regions related to immunity,\nneuronal development and function, and the main metabolic pathways governing neuronal\nmaturation and activity. A total of 17 genes involved in neuronal function, cell energy and\nimmunity, were identified by both DMP and DMR analyses. The most significant differentially\nmethylated gene was USP18, which plays an important role in neuronal development and\nneuroinflammation regulation. These findings suggest that ayahuasca use may cause lasting\nchanges in DNA methylation at sites of potential relevance for neuronal development and\nimmunity.","abstract":"Psychedelic use has been shown to improve human mental health and well-being for periods\nexceeding six months, and is a major area of interest in psychiatry and neuroscience. While little\nis known about the mechanisms of action of psychedelics, these improvements may be\nmediated by epigenetic processes. However, most preclinical assays have focused on acute or\npost-acute effects in animal models and cell cultures, and little is known about the specific\nepigenetic changes in human healthy volunteers. Here, we conducted a case-control study to\nevaluate the impact of ayahuasca - a classic serotonergic psychedelic containing N,N-\ndimethyltryptamine (DMT) - on the saliva methylome of ayahuasca users, whose time since self-\nadministration ranged from &amp;lt;1 week to 6 months, compared with a matched control group. DNA\nmethylation levels were quantified using the Infinium MethylationEPIC v2.0 BeadChips\n(Illumina). We observed significant differential methylation between the two groups at 494 CpG\nsites (DMPs) and a long-term effect of these methylation changes. DMPs functional analysis\nrevealed enrichment for terms related to immunity, angiogenesis and regulating cell cycle.\nDifferentially methylated region (DMR) analysis identified 57 regions related to immunity,\nneuronal development and function, and the main metabolic pathways governing neuronal\nmaturation and activity. A total of 17 genes involved in neuronal function, cell energy and\nimmunity, were identified by both DMP and DMR analyses. The most significant differentially\nmethylated gene was USP18, which plays an important role in neuronal development and\nneuroinflammation regulation. These findings suggest that ayahuasca use may cause lasting\nchanges in DNA methylation at sites of potential relevance for neuronal development and\nimmunity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008431","title":"Genome-wide SNP array genotyping in the FutureMS cohort","description":"The FutureMS study is a prospective, population-based inception cohort of individuals with newly diagnosed relapsing–remitting multiple sclerosis recruited across Scotland prior to initiation of disease-modifying therapy. This dataset comprises genome-wide single nucleotide polymorphism (SNP) genotyping generated using high-density array technology in FutureMS participants and matched controls.\n\nGenotype data were generated to enable analyses of genetic susceptibility, including HLA imputation and polygenic risk profiling, and to support integrative analyses with multimodal phenotyping. Participants are deeply characterised with clinical, radiological, and biomarker data, enabling investigation of genetic determinants of disease risk, heterogeneity, and progression.\n\nThese data form part of a broader multi-omic resource designed to investigate the role of host genetics and environmental exposures, including viral factors such as Epstein–Barr virus, in the pathogenesis and early course of multiple sclerosis.","abstract":"The FutureMS study is a prospective, population-based inception cohort of individuals with newly diagnosed relapsing–remitting multiple sclerosis recruited across Scotland prior to initiation of disease-modifying therapy. This dataset comprises genome-wide single nucleotide polymorphism (SNP) genotyping generated using high-density array technology in FutureMS participants and matched controls.\n\nGenotype data were generated to enable analyses of genetic susceptibility, including HLA imputation and polygenic risk profiling, and to support integrative analyses with multimodal phenotyping. Participants are deeply characterised with clinical, radiological, and biomarker data, enabling investigation of genetic determinants of disease risk, heterogeneity, and progression.\n\nThese data form part of a broader multi-omic resource designed to investigate the role of host genetics and environmental exposures, including viral factors such as Epstein–Barr virus, in the pathogenesis and early course of multiple sclerosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008432","title":"Genome-wide DNA Methylation, Transcriptomic, and Whole Exome Sequencing Data from Baseline FFPE Tumour Biopsies of Advanced Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors","description":"Immune checkpoint inhibitors (ICI) have transformed the treatment of advanced non-small cell lung cancer (NSCLC); however, response rates remain low and current biomarkers such as PD-L1 expression and tumor mutational burden (TMB) show limited predictive accuracy. This study investigated how baseline molecular profiles impact ICI response in a real-world cohort of advanced NSCLC patients.\n\nMulti-omics data were generated from diagnostic formalin-fixed paraffin-embedded (FFPE) primary tumor biopsies of 32 advanced NSCLC patients treated with anti-PD1/PD-L1 therapy in a real-world clinical setting. Genome-wide DNA methylation profiling was performed using the Illumina Infinium MethylationEPIC array (n=32). Transcriptomic profiling was conducted by bulk RNA sequencing (n=30). Somatic mutational profiling was obtained by whole exome sequencing (WES) using matched peripheral blood mononuclear cells (PBMCs) as germline controls (n=15). ICI response was assessed by computed tomography scan at 3 and 6 months after the first ICI dose according to RECIST 1.1 criteria.","abstract":"Immune checkpoint inhibitors (ICI) have transformed the treatment of advanced non-small cell lung cancer (NSCLC); however, response rates remain low and current biomarkers such as PD-L1 expression and tumor mutational burden (TMB) show limited predictive accuracy. This study investigated how baseline molecular profiles impact ICI response in a real-world cohort of advanced NSCLC patients.\n\nMulti-omics data were generated from diagnostic formalin-fixed paraffin-embedded (FFPE) primary tumor biopsies of 32 advanced NSCLC patients treated with anti-PD1/PD-L1 therapy in a real-world clinical setting. Genome-wide DNA methylation profiling was performed using the Illumina Infinium MethylationEPIC array (n=32). Transcriptomic profiling was conducted by bulk RNA sequencing (n=30). Somatic mutational profiling was obtained by whole exome sequencing (WES) using matched peripheral blood mononuclear cells (PBMCs) as germline controls (n=15). ICI response was assessed by computed tomography scan at 3 and 6 months after the first ICI dose according to RECIST 1.1 criteria.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008433","title":"Towards Objective Anal Cancer Screening: From Swab-Based Genome-Wide Methylation Marker Discovery to Novel Test Development","description":"Anal high-grade squamous intraepithelial lesions (HSIL-AIN2/3) are precursors to anal cancer, and early detection and treatment through screening is crucial for effective cancer prevention. Current guidelines recommend anal swab-based screening and highlight the need for objective biomarkers to improve risk stratification. While DNA methylation markers have shown strong potential in anal biopsies, their performance in anal swabs is reduced, likely due to sample-type dependency. This study aimed to identify a DNA methylation classifier specifically derived from anal swabs of men who have sex with men living with HIV (MSMLWH) to enhance diagnostic accuracy. Genome-wide methylation profiling was performed on anal swabs from 36 HSIL-AIN3 cases, 34 controls (&lt;low-grade squamous intraepithelial lesions (&lt;LSIL)), and 7 anal cancer patients using the 850K Infinium MethylationEPIC BeadChip (Illumina). Candidate CpG sites were selected via logistic regression with adaptive multi-group ridge penalties using co-data and an empirical Bayes approach (ecpc). The top candidate markers were validated using quantitative methylation-specific PCR (qMSP) on an independent series of 204 swabs to identify an optimal methylation classifier. Ecpc analysis identified 50 CpG sites with a combined area-under-the-curve (AUC) of 0.80. All ten candidate markers evaluated by qMSP showed significant increases in methylation levels associated with disease severity (p&lt;0.001). From these, a 3-gene methylation classifier was identified, demonstrating excellent performance with an AUC of 0.80 (95% confidence interval:0.72-0.88) in distinguishing HSIL-AIN3+ from ≤LSIL. This study identified a robust 3-gene methylation classifier with strong potential for detecting HSIL-AIN3 and anal cancer when applied to anal swabs from MSMLWH. ","abstract":"Anal high-grade squamous intraepithelial lesions (HSIL-AIN2/3) are precursors to anal cancer, and early detection and treatment through screening is crucial for effective cancer prevention. Current guidelines recommend anal swab-based screening and highlight the need for objective biomarkers to improve risk stratification. While DNA methylation markers have shown strong potential in anal biopsies, their performance in anal swabs is reduced, likely due to sample-type dependency. This study aimed to identify a DNA methylation classifier specifically derived from anal swabs of men who have sex with men living with HIV (MSMLWH) to enhance diagnostic accuracy. Genome-wide methylation profiling was performed on anal swabs from 36 HSIL-AIN3 cases, 34 controls (&lt;low-grade squamous intraepithelial lesions (&lt;LSIL)), and 7 anal cancer patients using the 850K Infinium MethylationEPIC BeadChip (Illumina). Candidate CpG sites were selected via logistic regression with adaptive multi-group ridge penalties using co-data and an empirical Bayes approach (ecpc). The top candidate markers were validated using quantitative methylation-specific PCR (qMSP) on an independent series of 204 swabs to identify an optimal methylation classifier. Ecpc analysis identified 50 CpG sites with a combined area-under-the-curve (AUC) of 0.80. All ten candidate markers evaluated by qMSP showed significant increases in methylation levels associated with disease severity (p&lt;0.001). From these, a 3-gene methylation classifier was identified, demonstrating excellent performance with an AUC of 0.80 (95% confidence interval:0.72-0.88) in distinguishing HSIL-AIN3+ from ≤LSIL. This study identified a robust 3-gene methylation classifier with strong potential for detecting HSIL-AIN3 and anal cancer when applied to anal swabs from MSMLWH. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-04-09T08:38:33+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008434","title":"a cohort-scale multi-omic atlas of human colon organoids and matched primary tissue biopsies.","description":"As part of the Human Cell Atlas, we present a cohort-scale multi-omic atlas of human colon organoids and matched primary tissue biopsies. Using single-nucleus RNA and ATAC-seq, we provide a systematic assessment of inter-individual variability and organoid fidelity. We benchmark organoid quality, discovering that while organoids adapt to a regenerative state and lack specific stromal signals, they robustly preserve donor-specific properties and cellular architecture. This resource and benchmarking method facilitate the use of high-fidelity organoids for large-scale studies of human biology, population heterogeneity, and precision medicine.","abstract":"As part of the Human Cell Atlas, we present a cohort-scale multi-omic atlas of human colon organoids and matched primary tissue biopsies. Using single-nucleus RNA and ATAC-seq, we provide a systematic assessment of inter-individual variability and organoid fidelity. We benchmark organoid quality, discovering that while organoids adapt to a regenerative state and lack specific stromal signals, they robustly preserve donor-specific properties and cellular architecture. This resource and benchmarking method facilitate the use of high-fidelity organoids for large-scale studies of human biology, population heterogeneity, and precision medicine.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-04-10T15:58:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008435","title":"Targeted_NanoSeq__Ulcerative_Colitis___PBMCs_","description":"Targeted NanoSeq of sorted PBMC cell populations from patients with ulcerative colitis.","abstract":"Targeted NanoSeq of sorted PBMC cell populations from patients with ulcerative colitis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008436","title":"Targeted_EMSeq___Liver","description":"Targeted EMSeq of liver samples","abstract":"Targeted EMSeq of liver samples","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008437","title":"Changes_in_mutational_landscape_in_tonsil_epithelia","description":"We are studying changes in the mutational landscape in tonsil epithelia from patients with recurrent tonsillitis","abstract":"We are studying changes in the mutational landscape in tonsil epithelia from patients with recurrent tonsillitis","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008438","title":"CAR-myeloid therapy","description":"Chimeric antigen receptor (CAR) T-cell therapies have transformed the treatment of haematological malignancies but show limited efficacy against solid tumours. Here we report results from a first-in-human phase 1 dose-escalation study of MT-302, an mRNA–lipid nanoparticle therapy that programs myeloid cells in vivo to express a TROP2-directed CD89 CAR, bypassing the need for ex vivo cell manufacturing. Twenty-seven heavily pretreated patients with advanced epithelial cancers received biweekly intravenous infusions of MT-302 (0.005–0.15 mg kg⁻¹). Repeat dosing was feasible and well tolerated (mean 4 infusions; maximum 22), with limited RNA-associated reactogenicity and no grade ≥3 cytokine release syndrome; one reversible grade 4 immune effector cell-associated neurotoxicity syndrome (ICANS) event occurred at 0.15 mg kg⁻¹. In paired blood preparations and tumour biopsies, MT-302 induced CAR expression in myeloid and natural killer cells, increased effector cytokine and chemokine production, and remodelled the tumour microenvironment through pro-inflammatory macrophage polarisation, enhanced antigen presentation and T cell infiltration demonstrated by spatial transcriptomics. One patient with hormone receptor-positive breast cancer achieved a confirmed partial response and remained on therapy for 16 months. These results establish proof of mechanism for systemically delivered in vivo CAR programming and support further clinical development of MT-302.","abstract":"Chimeric antigen receptor (CAR) T-cell therapies have transformed the treatment of haematological malignancies but show limited efficacy against solid tumours. Here we report results from a first-in-human phase 1 dose-escalation study of MT-302, an mRNA–lipid nanoparticle therapy that programs myeloid cells in vivo to express a TROP2-directed CD89 CAR, bypassing the need for ex vivo cell manufacturing. Twenty-seven heavily pretreated patients with advanced epithelial cancers received biweekly intravenous infusions of MT-302 (0.005–0.15 mg kg⁻¹). Repeat dosing was feasible and well tolerated (mean 4 infusions; maximum 22), with limited RNA-associated reactogenicity and no grade ≥3 cytokine release syndrome; one reversible grade 4 immune effector cell-associated neurotoxicity syndrome (ICANS) event occurred at 0.15 mg kg⁻¹. In paired blood preparations and tumour biopsies, MT-302 induced CAR expression in myeloid and natural killer cells, increased effector cytokine and chemokine production, and remodelled the tumour microenvironment through pro-inflammatory macrophage polarisation, enhanced antigen presentation and T cell infiltration demonstrated by spatial transcriptomics. One patient with hormone receptor-positive breast cancer achieved a confirmed partial response and remained on therapy for 16 months. These results establish proof of mechanism for systemically delivered in vivo CAR programming and support further clinical development of MT-302.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008439","title":"Genomic platform specific polygenic risk scores impact breast cancer risk stratification","description":"Background: At present, there is no consensus on which genotyping platform should serve as the standard for clinical polygenic risk score (PRS) implementation. Previous studies have compared the overall performance and concordance of different genotyping and sequencing technologies; however, these analyses have generally averaged the results over the whole genome. We evaluated differences in a 313-variant breast cancer PRS (PRS313) across genomic platforms and their impact on risk stratification.\n\nMethods: We compare PRS313 derived from genotyping arrays (Global Screening Array [GSA], OncoArray-500K [OncoArray], Global Diversity Array [GDA], custom Axiom_PrecipV1 array [ThermoFisher]) and low-coverage genome sequencing (lc-WGS) in 2 cell lines and 92 individuals. Probes are designed for all variants on ThermoFisher (success rate: 259/313). Sanger sequencing profiles indels. Concordance of high-risk classification (PRS313scoresum &gt; 0.6) across platforms is assessed using Kappa statistics.\n\nResults: In saliva samples, indel concordance with Sanger sequencing varies widely (Kappa: 0.007-1.000). PRS313-ThermoFisher is predictable from other platforms using linear models, despite systematic differences. Greater agreement is observed between arrays with high imputation overlap (e.g., GDA ~ GSA slope=0.986). Agreement in high-risk classification before mean correction is moderate (Fleiss's Kappa=0.552) and improves after mean correction (Kappa=0.650). Arrays with similar designs show higher agreement before mean correction (Kappa=0.745). Mean correction narrows high-risk proportions from 4-45% to 15-21%. Overall, 26 of 92 samples are classified as high risk on at least one platform, but only 7 are high risk across all. When restricting to identical variants across all platforms for PRS313 calculation, the corresponding number of high-risk individuals are 24 and 11.\n\nConclusion: Our findings demonstrate that platform-specific variability can influence PRS313 estimates to potentially reclassify individuals around clinically relevant thresholds.","abstract":"Background: At present, there is no consensus on which genotyping platform should serve as the standard for clinical polygenic risk score (PRS) implementation. Previous studies have compared the overall performance and concordance of different genotyping and sequencing technologies; however, these analyses have generally averaged the results over the whole genome. We evaluated differences in a 313-variant breast cancer PRS (PRS313) across genomic platforms and their impact on risk stratification.\n\nMethods: We compare PRS313 derived from genotyping arrays (Global Screening Array [GSA], OncoArray-500K [OncoArray], Global Diversity Array [GDA], custom Axiom_PrecipV1 array [ThermoFisher]) and low-coverage genome sequencing (lc-WGS) in 2 cell lines and 92 individuals. Probes are designed for all variants on ThermoFisher (success rate: 259/313). Sanger sequencing profiles indels. Concordance of high-risk classification (PRS313scoresum &gt; 0.6) across platforms is assessed using Kappa statistics.\n\nResults: In saliva samples, indel concordance with Sanger sequencing varies widely (Kappa: 0.007-1.000). PRS313-ThermoFisher is predictable from other platforms using linear models, despite systematic differences. Greater agreement is observed between arrays with high imputation overlap (e.g., GDA ~ GSA slope=0.986). Agreement in high-risk classification before mean correction is moderate (Fleiss's Kappa=0.552) and improves after mean correction (Kappa=0.650). Arrays with similar designs show higher agreement before mean correction (Kappa=0.745). Mean correction narrows high-risk proportions from 4-45% to 15-21%. Overall, 26 of 92 samples are classified as high risk on at least one platform, but only 7 are high risk across all. When restricting to identical variants across all platforms for PRS313 calculation, the corresponding number of high-risk individuals are 24 and 11.\n\nConclusion: Our findings demonstrate that platform-specific variability can influence PRS313 estimates to potentially reclassify individuals around clinically relevant thresholds.","study_type":"Other","pubmed_ids":[41387625],"external_links":null,"is_released":true,"released_date":"2026-04-20T10:48:26+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008440","title":"Multi-omic data of subjects of FUSION study","description":"Finland-United States Investigation of NIDDM Genetics (FUSION) Study has sought to understand the genetic basis of type 2 diabetes (T2D) and diabetes-related traits including glucose, insulin, lipid levels, and obesity. We have performed extensive multi-omic characterization of the study subjects, including SNP array genotyping, whole genome/exome DNA sequencing of blood/tissue/iPSC cells generated from fibroblast, as well as RNAs. The study has provided crucial data for understanding molecular and cellular mechanisms of the disease-causing variants and their respective target genes. This set of data will be a valuable resource to the T2D community.","abstract":"Finland-United States Investigation of NIDDM Genetics (FUSION) Study has sought to understand the genetic basis of type 2 diabetes (T2D) and diabetes-related traits including glucose, insulin, lipid levels, and obesity. We have performed extensive multi-omic characterization of the study subjects, including SNP array genotyping, whole genome/exome DNA sequencing of blood/tissue/iPSC cells generated from fibroblast, as well as RNAs. The study has provided crucial data for understanding molecular and cellular mechanisms of the disease-causing variants and their respective target genes. This set of data will be a valuable resource to the T2D community.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-10-01T09:59:15.387501+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008441","title":"Sensitive detection of MYCN amplified neuroblastoma in blood samples with structural variants using whole genome sequencing","description":"MYCN high amplification in neuroblastoma indicates a high-risk diagnosis. Although this feature is routinely detected using tumor whole genome sequencing followed by copy number analysis, it remains unclear whether MYCN amplification can be detected in blood samples. Leveraging on recent progress in the error profiling of structural alterations (SVs), we hypothesize that copy number analysis coupled with SV detection can enable sensitive detection of MYCN amplification in blood samples. By using childhood neuroblastoma cohorts from three institutions, we demonstrate that standard whole genome sequencing (30-100X) of blood samples enables detection of MYCN amplification in 64% of cases with limit of detection as low as 0.01% and SV markers are superior to conventional copy number markers. Further, we demonstrate that buccal samples collected at diagnosis are less affected by circulating tumor DNAs for MYCN amplified neuroblastoma. Together, our findings indicate the power of SV analysis in liquid biopsies to ascertain high risk MYCN amplified neuroblastoma.","abstract":"MYCN high amplification in neuroblastoma indicates a high-risk diagnosis. Although this feature is routinely detected using tumor whole genome sequencing followed by copy number analysis, it remains unclear whether MYCN amplification can be detected in blood samples. Leveraging on recent progress in the error profiling of structural alterations (SVs), we hypothesize that copy number analysis coupled with SV detection can enable sensitive detection of MYCN amplification in blood samples. By using childhood neuroblastoma cohorts from three institutions, we demonstrate that standard whole genome sequencing (30-100X) of blood samples enables detection of MYCN amplification in 64% of cases with limit of detection as low as 0.01% and SV markers are superior to conventional copy number markers. Further, we demonstrate that buccal samples collected at diagnosis are less affected by circulating tumor DNAs for MYCN amplified neuroblastoma. Together, our findings indicate the power of SV analysis in liquid biopsies to ascertain high risk MYCN amplified neuroblastoma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-04-20T22:27:22+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008442","title":"NanoSeq___Characterising_smoking_effects_on_the_AhR_ihibitors_in_human_basal_cells_","description":"The aim of this study is to investigate the mechanisms of the increased mutation burden induced by smoking related mutagens (e.g. Benzo-a-pyrene). Here we use AhR inhibitors to assess how AhR pathway is involved in the mutagenic effects in human proximal and distal airways.  ","abstract":"The aim of this study is to investigate the mechanisms of the increased mutation burden induced by smoking related mutagens (e.g. Benzo-a-pyrene). Here we use AhR inhibitors to assess how AhR pathway is involved in the mutagenic effects in human proximal and distal airways.  ","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008443","title":"Host genotyping data from Dutch patients with and without cerebral infarction complicating pneumococcal meningitis","description":"Cerebral infarction is a frequent and devastating complication of pneumococcal meningitis, yet the underlying host mechanisms remain poorly defined. We performed a genome-wide association study in adults with pneumococcal meningitis to identify genetic variants associated with cerebral infarction. In this study, we included 744 patients with pneumococal meningitis from the Dutch MeninGene cohort. Samples were collected from adults (&gt;16 yrs) patients with CSF confirmed bacterial meningitis in the Netherlands between 2006 and 2015.","abstract":"Cerebral infarction is a frequent and devastating complication of pneumococcal meningitis, yet the underlying host mechanisms remain poorly defined. We performed a genome-wide association study in adults with pneumococcal meningitis to identify genetic variants associated with cerebral infarction. In this study, we included 744 patients with pneumococal meningitis from the Dutch MeninGene cohort. Samples were collected from adults (&gt;16 yrs) patients with CSF confirmed bacterial meningitis in the Netherlands between 2006 and 2015.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008444","title":"Methylation Analysis of iPSC model of MPNST progression","description":"Methylation analysis of the cells generated in our iPSC cellular model for the study of Malignant Peripheral Nerve Sheath Tumors (MPNST) progression.","abstract":"Methylation analysis of the cells generated in our iPSC cellular model for the study of Malignant Peripheral Nerve Sheath Tumors (MPNST) progression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008445","title":"Mapping the lineage-retained antigen landscape in neuroblastoma","description":"Neuroblastoma is among the deadliest pediatric solid tumors, and relapse is frequently driven by lineage plasticity between adrenergic (ADRN) and mesenchymal (MES) cell states that escape conventional and targeted therapies. This project aims to identify tumor antigens that are retained across both lineage states and are therefore suitable for T-cell–based immunotherapy resistant to lineage switching, including non-canonical antigens derived from the \"dark proteome.\" To support this aim, we generated paired RNA-sequencing and ribosome profiling (Ribo-seq) data from neuroblastoma cell lines, patient-derived tumor organoids, and primary patient tumors spanning ADRN and MES states. The RNA-seq data enable custom transcriptome assembly to recover non-reference and non-canonical transcripts, while Ribo-seq maps actively translated canonical and non-canonical open reading frames at codon resolution. Together these data provide the molecular substrate for systematic discovery of lineage-retained, translation-supported neuroblastoma antigens.","abstract":"Neuroblastoma is among the deadliest pediatric solid tumors, and relapse is frequently driven by lineage plasticity between adrenergic (ADRN) and mesenchymal (MES) cell states that escape conventional and targeted therapies. This project aims to identify tumor antigens that are retained across both lineage states and are therefore suitable for T-cell–based immunotherapy resistant to lineage switching, including non-canonical antigens derived from the \"dark proteome.\" To support this aim, we generated paired RNA-sequencing and ribosome profiling (Ribo-seq) data from neuroblastoma cell lines, patient-derived tumor organoids, and primary patient tumors spanning ADRN and MES states. The RNA-seq data enable custom transcriptome assembly to recover non-reference and non-canonical transcripts, while Ribo-seq maps actively translated canonical and non-canonical open reading frames at codon resolution. Together these data provide the molecular substrate for systematic discovery of lineage-retained, translation-supported neuroblastoma antigens.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-05-01T13:42:00+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008446","title":"BCG-DENMARK-SENIOR DNA methylation","description":null,"abstract":"DNA methylation data from the BCG-DENMARK-SENIOR cohort.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008447","title":"Homo_sapiens__GRCh38_15_plus_hs38d1___ensembl_90_transcriptome___star_","description":"Spatial Characterisation of the Human Pancreas in Type 1 Diabetes at Single Cell Resolution","abstract":"This project uses high-resolution Xenium spatial transcriptomics to characterise the cellular composition and organisation of the human pancreas in the context of type 1 diabetes (T1D). The aim is to map endocrine, exocrine, stromal, and immune cell populations within intact tissue and define their spatial relationships. We focus on identifying cell-type-specific transcriptional programs and potential cell–cell communication interactions within the pancreatic microenvironment. The data will be used to generate a spatially resolved atlas of pancreatic tissue and to support integrative analyses with complementary single-cell datasets. Overall, this work aims to provide a detailed framework for studying tissue architecture and cellular interactions relevant to T1D.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008448","title":"This is a test to check the WEBIN functionality","description":"Checking WEBIN functionality","abstract":"Checking WEBIN functionality","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008449","title":"Single-nucleus sequencing of fresh-frozen large cell neuroendocrine carcinoma","description":" \tHigh-grade pancreatic neuroendocrine carcinoma (panNEC) is a rare, aggressive cancer with limited tissue availability. Single-nucleus transcriptomics of five large-cell panNECs revealed two interesting neuroendocrine cell states: one highly proliferative with an aberrant brain-specific neuronal differentiation program and another stress-responsive state enriched for heat stress, hypoxia, and glycolysis. Our findings suggest potential therapeutic vulnerabilities, highlighting the need to evaluate the efficacy of combination therapies.","abstract":" \tHigh-grade pancreatic neuroendocrine carcinoma (panNEC) is a rare, aggressive cancer with limited tissue availability. Single-nucleus transcriptomics of five large-cell panNECs revealed two interesting neuroendocrine cell states: one highly proliferative with an aberrant brain-specific neuronal differentiation program and another stress-responsive state enriched for heat stress, hypoxia, and glycolysis. Our findings suggest potential therapeutic vulnerabilities, highlighting the need to evaluate the efficacy of combination therapies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-05-11T16:18:37+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008450","title":"Born in Bradford HRC-Imputed Genotyping Data","description":"This study contains genome-wide genotyping data for 16,246 participants of the Born in Bradford (BiB) cohort. Data includes participants genotyped on the Illumina Global Screening Array (GSA) and the Human CoreExome (HCE) array and separated by ancestry (European and South Asian). All data has been imputed using the Haplotype Reference Consortium (HRC) reference panel and is provided in PLINK binary format.","abstract":"This study contains genome-wide genotyping data for 16,246 participants of the Born in Bradford (BiB) cohort. Data includes participants genotyped on the Illumina Global Screening Array (GSA) and the Human CoreExome (HCE) array and separated by ancestry (European and South Asian). All data has been imputed using the Haplotype Reference Consortium (HRC) reference panel and is provided in PLINK binary format.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008451","title":"Genome-wide DNA Methylation, Transcriptomic, and Whole Exome Sequencing Data from Baseline FFPE Tumour Biopsies of Renal Cell Carcinoma Patients Treated with Immune Checkpoint Inhibitors","description":"This study investigated how baseline molecular profiles impact response to Immune checkpoint inhibitors (ICI) response in Renal Cell Carcinoma (RCC) patients.\n\nMulti-omics data were generated from diagnostic formalin-fixed paraffin-embedded (FFPE) primary tumor biopsies of a cohort of 33 RCC patients treated with anti-PD1/PD-L1/CTLA4 therapy. Genome-wide DNA methylation profiling was performed using the Illumina Infinium MethylationEPIC array (n=32). Transcriptomic profiling was conducted by bulk RNA sequencing (n=32). Somatic mutational profiling was obtained by whole exome sequencing (WES) (n=20). ICI response was assessed by computed tomography scan at 3 months after the first ICI dose according to RECIST 1.1 criteria.","abstract":"This study investigated how baseline molecular profiles impact response to Immune checkpoint inhibitors (ICI) response in Renal Cell Carcinoma (RCC) patients.\n\nMulti-omics data were generated from diagnostic formalin-fixed paraffin-embedded (FFPE) primary tumor biopsies of a cohort of 33 RCC patients treated with anti-PD1/PD-L1/CTLA4 therapy. Genome-wide DNA methylation profiling was performed using the Illumina Infinium MethylationEPIC array (n=32). Transcriptomic profiling was conducted by bulk RNA sequencing (n=32). Somatic mutational profiling was obtained by whole exome sequencing (WES) (n=20). ICI response was assessed by computed tomography scan at 3 months after the first ICI dose according to RECIST 1.1 criteria.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008452","title":"Stratton_Somatic_mutations_in_benign_and_malignant_kidney_diseases_TargetedNanoSeq","description":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. Here, we will study somatic mutations in benign and malignant kidney tissue samples, including their matched normal tissues, to better understand mutational signatures, burdens, driver selection within these conditions. ","abstract":"The Stratton team uses DNA sequencing for somatic mutations to advance understanding of the causes of cancer. In particular, the investigation of “mutational signatures”, which report the mutational processes operative over the lifetime of each individual, to understand whether they are generated by endogenous or exogenous exposures and the extent to which these vary between human populations. Our work brings together global cancer epidemiology and genomics and is particularly characterised by large-scale multinational studies. \n\nSomatic mutational profiles in oligomutated and polyclonal tissues such as the kidney have not been well studied using whole-genome sequencing as it has been previously cost-prohibitive due to the sequencing error rates of WGS. This study will focus on applying duplex sequencing to study benign and malignant kidney conditions, and also apply WGS and whole-exome sequencing to study possible clonal populations within the kidneys (and their matched controls such as blood).   ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008453","title":"CG_Tongue_P_BW_Spatial_Behjati_Managed","description":"Beckwith-Wiedemann syndrome (BWS) is a congenital disorder associated with overgrowth and predisposition to certain cancers, caused by abnormalities in the methylation of regulatory regions on chr11p. Patients often present with hemi-hypertrophy, i.e., overgrowth of certain body parts, such as the tongue, only on one side of their body. Tongue resection surgery is often done to improve patients’ life quality. In this study, we perform multimodal sequencing of resected tongues to compare the overgrown and non-overgrown sides to understand why the phenotype is seen only on one side of the body. By comparing the left and right side of the body, we can understand the lineage relationships of cells with alterations in chr11p methylation and the transcriptional consequences of those changes depending on the context (overgrown vs non-overgrown side).","abstract":"Beckwith-Wiedemann syndrome (BWS) is a congenital disorder associated with overgrowth and predisposition to certain cancers, caused by abnormalities in the methylation of regulatory regions on chr11p. Patients often present with hemi-hypertrophy, i.e., overgrowth of certain body parts, such as the tongue, only on one side of their body. Tongue resection surgery is often done to improve patients’ life quality. In this study, we perform multimodal sequencing of resected tongues to compare the overgrown and non-overgrown sides to understand why the phenotype is seen only on one side of the body. By comparing the left and right side of the body, we can understand the lineage relationships of cells with alterations in chr11p methylation and the transcriptional consequences of those changes depending on the context (overgrown vs non-overgrown side).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008454","title":"Time course of scRNA and ATAC along two oscillations of the segmentation clock in iPSC-derived presomitic mesoderm","description":"RNA levels and chromatin accessibility were assayed in a time course of the segmentation clock in iPSC-derived presomitic mesoderm. Cells were snap-frozen, then nuclei isolated and fixed in glyoxal and library generated according to the SUM-seq protocol (Yildiz et al. DOI: 10.1038/s41596-025-01310-0). Libraries were sequenced (paired-end) on AVITI.","abstract":"time series design","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008455","title":"Pharmacogenomic diversity across 12 understudied African populations from whole-exome sequencing","description":"Cohort study characterizing pharmacogenomic diversity across 12 previously understudied African populations. 127 individuals were recruited from the AIBST biobank under MRCZ ethics approval, spanning Kikuyu, Luo, Maasai and psychiatric-patient groups (Kenya); two ethnicity-unspecified cohorts (Tanzania); Igbo, Hausa, Yoruba (Nigeria); Venda (South Africa); and San and Shona (Zimbabwe). The cohort emphasizes ethnic groups absent or underrepresented in 1000 Genomes, gnomAD, and AGVP. Characteristics under investigation are pharmacogene variant frequencies, population-level differentiation, novel-variant pathogenicity, and predicted metabolizer phenotypes relevant to HIV, tuberculosis, and malaria therapeutics. Participants are healthy adults; this is not a case-control design. Data sharing is consented under AIBST/MRCZ terms for biomedical research, broadly aligned with Data Use Ontology codes for general research use (GRU) and health/medical/biomedical research (HMB).","abstract":"Cohort study characterizing pharmacogenomic diversity across 12 previously understudied African populations. 127 individuals were recruited from the AIBST biobank under MRCZ ethics approval, spanning Kikuyu, Luo, Maasai and psychiatric-patient groups (Kenya); two ethnicity-unspecified cohorts (Tanzania); Igbo, Hausa, Yoruba (Nigeria); Venda (South Africa); and San and Shona (Zimbabwe). The cohort emphasizes ethnic groups absent or underrepresented in 1000 Genomes, gnomAD, and AGVP. Characteristics under investigation are pharmacogene variant frequencies, population-level differentiation, novel-variant pathogenicity, and predicted metabolizer phenotypes relevant to HIV, tuberculosis, and malaria therapeutics. Participants are healthy adults; this is not a case-control design. Data sharing is consented under AIBST/MRCZ terms for biomedical research, broadly aligned with Data Use Ontology codes for general research use (GRU) and health/medical/biomedical research (HMB).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008456","title":"H3Africa - Pharmacogenomic diversity across 12 understudied African populations from whole-exome sequencing","description":"Cohort study characterizing pharmacogenomic diversity across 12 previously understudied African populations. 127 individuals were recruited from the AIBST biobank under MRCZ ethics approval, spanning Kikuyu, Luo, Maasai and psychiatric-patient groups (Kenya); two ethnicity-unspecified cohorts (Tanzania); Igbo, Hausa, Yoruba (Nigeria); Venda (South Africa); and San and Shona (Zimbabwe). The cohort emphasizes ethnic groups absent or underrepresented in 1000 Genomes, gnomAD, and AGVP. Characteristics under investigation are pharmacogene variant frequencies, population-level differentiation, novel-variant pathogenicity, and predicted metabolizer phenotypes relevant to HIV, tuberculosis, and malaria therapeutics. Participants are healthy adults; this is not a case-control design. Data sharing is consented under AIBST/MRCZ terms for biomedical research, broadly aligned with Data Use Ontology codes for general research use (GRU) and health/medical/biomedical research (HMB).\n","abstract":"Cohort study characterizing pharmacogenomic diversity across 12 previously understudied African populations. 127 individuals were recruited from the AIBST biobank under MRCZ ethics approval, spanning Kikuyu, Luo, Maasai and psychiatric-patient groups (Kenya); two ethnicity-unspecified cohorts (Tanzania); Igbo, Hausa, Yoruba (Nigeria); Venda (South Africa); and San and Shona (Zimbabwe). The cohort emphasizes ethnic groups absent or underrepresented in 1000 Genomes, gnomAD, and AGVP. Characteristics under investigation are pharmacogene variant frequencies, population-level differentiation, novel-variant pathogenicity, and predicted metabolizer phenotypes relevant to HIV, tuberculosis, and malaria therapeutics. Participants are healthy adults; this is not a case-control design. Data sharing is consented under AIBST/MRCZ terms for biomedical research, broadly aligned with Data Use Ontology codes for general research use (GRU) and health/medical/biomedical research (HMB).\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-05-25T11:04:58+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008457","title":"RNA-seq analysis of TEAD inhibition in pleural mesothelioma","description":"The Hippo pathway is frequently deregulated in pleural mesothelioma (PM), contributing significantly to tumor progression. The Hippo downstream effector, the TEAD-YAP/TAZ transcriptional complex, is a highly attractive therapeutic target, particularly TEAD transcription factors that can be targeted with available inhibitors. However, the respective roles of the four TEAD paralogs, TEAD1-4, and their contributions in PM remain poorly understood.\n\nIn this study, we conducted a comprehensive assessment of TEAD paralogs in PM. TEAD1 was identified as the most highly expressed TEAD gene in four independent PM cohorts. This over-representation was conserved at the protein level, whereas TEAD2 protein expression was weak. Using a large series of well-characterized patient-derived primary PM cell lines representative of tumor heterogeneity, together with seven TEAD inhibitors with defined in cellulo TEAD1-4 specificities, we showed that TEAD inhibition markedly affects cell viability in a wide range of cell lines, independently of Hippo pathway inactivation or YAP/TAZ-TEAD activation.\n\nImportantly, by integrating inhibitor screening, combined silencing of TEAD1-4 by RNA interference, and gene-editing dependency dataset analysis, TEAD1 emerged as the main contributor to cell viability in PM. However, effective inhibition of viability required simultaneous inhibition of at least TEAD1, TEAD3 and TEAD4. The RNA-seq data submitted here were generated as part of the transcriptomic profiling performed to characterize the molecular consequences of TEAD inhibition. These analyses showed that TEAD inhibition not only impacted cell-cycle programs but also activated inflammatory and interferon signaling pathways.\n\nOverall, this study clarifies the contribution of TEAD1-4 paralogs in PM, reinforces the therapeutic relevance of TEAD inhibition, and provides guidance for the development of future TEAD-targeted treatment strategies in this cancer.","abstract":"The Hippo pathway is frequently deregulated in pleural mesothelioma (PM), contributing significantly to tumor progression. The Hippo downstream effector, the TEAD-YAP/TAZ transcriptional complex, is a highly attractive therapeutic target, particularly TEAD transcription factors that can be targeted with available inhibitors. However, the respective roles of the four TEAD paralogs, TEAD1-4, and their contributions in PM remain poorly understood.\n\nIn this study, we conducted a comprehensive assessment of TEAD paralogs in PM. TEAD1 was identified as the most highly expressed TEAD gene in four independent PM cohorts. This over-representation was conserved at the protein level, whereas TEAD2 protein expression was weak. Using a large series of well-characterized patient-derived primary PM cell lines representative of tumor heterogeneity, together with seven TEAD inhibitors with defined in cellulo TEAD1-4 specificities, we showed that TEAD inhibition markedly affects cell viability in a wide range of cell lines, independently of Hippo pathway inactivation or YAP/TAZ-TEAD activation.\n\nImportantly, by integrating inhibitor screening, combined silencing of TEAD1-4 by RNA interference, and gene-editing dependency dataset analysis, TEAD1 emerged as the main contributor to cell viability in PM. However, effective inhibition of viability required simultaneous inhibition of at least TEAD1, TEAD3 and TEAD4. The RNA-seq data submitted here were generated as part of the transcriptomic profiling performed to characterize the molecular consequences of TEAD inhibition. These analyses showed that TEAD inhibition not only impacted cell-cycle programs but also activated inflammatory and interferon signaling pathways.\n\nOverall, this study clarifies the contribution of TEAD1-4 paralogs in PM, reinforces the therapeutic relevance of TEAD inhibition, and provides guidance for the development of future TEAD-targeted treatment strategies in this cancer.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008458","title":"Liver tumors in vascular liver disorders","description":"Primary liver tumors arising in vascular liver disorders are diagnostically challenging and their molecular features remain incompletely characterized. This study includes genomic and transcriptomic profiling of liver tumors and matched non-tumoral liver samples from patients with vascular liver disorders. Whole-genome sequencing, whole-exome sequencing and/or RNA sequencing were used to refine pathological classification, identify driver alterations, characterize copy-number and transcriptomic profiles, and support molecular diagnosis.","abstract":"Primary liver tumors arising in vascular liver disorders are diagnostically challenging and their molecular features remain incompletely characterized. This study includes genomic and transcriptomic profiling of liver tumors and matched non-tumoral liver samples from patients with vascular liver disorders. Whole-genome sequencing, whole-exome sequencing and/or RNA sequencing were used to refine pathological classification, identify driver alterations, characterize copy-number and transcriptomic profiles, and support molecular diagnosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008459","title":"NK_CD8_IMMERSE_CROPseq","description":"Parse CRISPR detect scRNAseq on human NK and CD8 T cells, pilot with a small bespoke guide library using different treatment and stimulations.\nThis data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/\nThis data has been described in the following article and its further analysis can be freely submitted for publication. For information on the proper use of data shared by the Wellcome Trust Sanger Institute (including information on acknowledgement), please see http://www.sanger.ac.uk/datasharing/\n","abstract":"Pilot study to determine is Parse CRISPR detect combined with Evercode WT can be used in a CROPseq experiment on human CD8 and NK cells. A small library of gene targeting and safe targeting guides were applied to the cells which were treated and stimulated with various agents. Libraries for whole transcriptome and CRISPR guides are present.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008460","title":"Born in Bradford DNA Methylation Data","description":"The Born in Bradford cohort DNA methylation data was generated using the Illumina Infinium MethylationEPIC Array v1.0, and contains methylation data for 1883 participants; 933 mothers and 950 children.","abstract":"The Born in Bradford cohort DNA methylation data was generated using the Illumina Infinium MethylationEPIC Array v1.0, and contains methylation data for 1883 participants; 933 mothers and 950 children.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008461","title":"Subclonal evolution in pleural mesothelioma","description":"A better understanding of intratumor heterogeneity in pleural mesothelioma (PM) is crucial to implementing precision medicine for this deadly cancer. Using single-cell RNA sequencing approaches on tumor samples and derived primary cell lines, we defined four phenotypic cell types, related to overall survival in larger bulk cohorts: epithelioid, sarcomatoid, intermediate, and non-differentiated. Some tumor samples showed intratumor phenotypic heterogeneity, always associated with subclonal evolution, in which sarcomatoid cells emerged from parental cells with an intermediate phenotype following the acquisition of copy-number variations. Subclones were conserved in cell lines and retained their specific phenotypes, suggesting high phenotypic heritability. Spatial transcriptomics validated the link between phenotypic and subclonal evolution, showing that subclonal cells were colocalized and exhibited specific morphologies within the tumor tissue. Our study provides a novel and comprehensive single-cell profiling of PM tumor cells and reveals a strong link between phenotypic evolution, clonal architecture, and tumor spatial organization.","abstract":"A better understanding of intratumor heterogeneity in pleural mesothelioma (PM) is crucial to implementing precision medicine for this deadly cancer. Using single-cell RNA sequencing approaches on tumor samples and derived primary cell lines, we defined four phenotypic cell types, related to overall survival in larger bulk cohorts: epithelioid, sarcomatoid, intermediate, and non-differentiated. Some tumor samples showed intratumor phenotypic heterogeneity, always associated with subclonal evolution, in which sarcomatoid cells emerged from parental cells with an intermediate phenotype following the acquisition of copy-number variations. Subclones were conserved in cell lines and retained their specific phenotypes, suggesting high phenotypic heritability. Spatial transcriptomics validated the link between phenotypic and subclonal evolution, showing that subclonal cells were colocalized and exhibited specific morphologies within the tumor tissue. Our study provides a novel and comprehensive single-cell profiling of PM tumor cells and reveals a strong link between phenotypic evolution, clonal architecture, and tumor spatial organization.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008462","title":"Time course of scCUT&Tag for H3K27Ac along two oscillations of the segmentation clock in iPSC-derived presomitic mesoderm","description":"H3K27Ac levels were assayed in a time course of the segmentation clock in iPSC-derived presomitic mesoderm. Cells were snap-frozen, then nuclei isolated and fixed in PFA and treated for multiplexed scCUT&amp;Tag. Libraries were sequenced (paired-end) on Illumina NextSeq 500.","abstract":"time series design","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008463","title":"Time course of scRNA-seq along two oscillations of the segmentation clock in iPSC-derived presomitic mesoderm","description":"RNA levels were assayed in a time course of the segmentation clock in iPSC-derived presomitic mesoderm. Cells were fixed using the Scale Biosciences Fixation Kit and treated for scRNA-seq using the Scale Biosciences 3-level scRNA-sequence kit according to the manufacturer's protocol. Libraries were sequenced (paired-end) on Illumina Nextseq 2000.","abstract":"time series design","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008464","title":"CG_Reproductive_A_MV_EndoDA_Spatial_Vento_Managed","description":"A collaborative multi-institute project, using single cell atlasing and spatial techniques on endometrium samples and endometriosis cases to investigate endometriosis disease mechanisms, and endometrial cell biology (BH = 22/0009 - Oxford).","abstract":"A collaborative multi-institute project, using single cell atlasing and spatial techniques on endometrium samples and endometriosis cases to investigate endometriosis disease mechanisms, and endometrial cell biology (BH = 22/0009 - Oxford).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008465","title":"OAC Operable Cohorts RNASeq Normal Tissue","description":null,"abstract":"Please see our related publication, 'Tumour DNA methylation subtypes and expression levels of CFISH (CXCL8, FCN1, IFI30, SLC11A1, HLA-DRA) predict response and overall survival to immunochemotherapy.'","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008466","title":"WGS__Prominent__oesophagus","description":"Oesophageal carcinoma incidence varies across the world.  We wish to investigate the reasons behind this using high depth sequencing of normal oesophageal epithelium.","abstract":"Oesophageal carcinoma incidence varies across the world.  We wish to investigate the reasons behind this using high depth sequencing of normal oesophageal epithelium.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008467","title":"Heterogeneous endocrine cell composition defines human islet functional phenotypes","description":null,"abstract":"Phenotyping and genotyping initiatives within the Integrated Islet Distribution Program (IIDP), the largest source of human islets for research in the U.S., provide standardized assessment of islet preparations distributed to researchers and enable the integration of multiple data types. Data from islets of the first 299 organ donors without diabetes analyzed using this pipeline highlights substantial heterogeneity in islet cell composition associated with hormone secretory traits, sex, reported race and ethnicity, genetically predicted ancestry, and genetic risk for type 2 diabetes (T2D). While α and β cell composition influenced insulin and glucagon secretory traits, the abundance of δ cells showed the strongest association with insulin secretion and was also associated with the genetic risk score (GRS) for T2D. These findings have important implications for understanding mechanisms underlying diabetes heterogeneity and islet dysfunction and may provide insight into strategies for personalized medicine and β cell replacement therapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-06-17T02:45:39+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008468","title":"TG001_10_year_analysis_WGS_LCMB","description":"The mutational landscape of haematopoietic cells will be characterized by LCMB-WGS","abstract":"The mutational landscape of haematopoietic cells will be characterized by LCMB-WGS","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008469","title":"OPEN_IBD_Genomics","description":"Open-IBD will deliver a step-change in our ability to build robust therapeutic hypotheses and identify biomarkers for inflammatory bowel disease (IBD; encompassing Crohn’s disease (CD) and ulcerative colitis (UC)) susceptibility and progression. We will recruit newly diagnose IBD patients and collect blood/gut tissue samples to generate whole genome sequencing data at 30X sequencing coverage. ","abstract":"Open-IBD, a longitudinal multi-omics inception cohort in IBD to address this unmet need. Studying the biology of IBD from the point of diagnosis, without the confounders of time, uncontrolled inflammation and exposure to multiple therapies, provides an unparalleled opportunity for deriving biomarkers and mechanistic insights that aid the discovery and validation of therapeutic targets in IBD. 1,000 IBD research participants will be recruited from diagnostic referral pathways between primary and secondary care from seven NHS sites by co-applicants across the United Kingdom. Open-IBD focuses on deriving blood and tissue single-cell transcriptome, alongside genomics data and gut and stool microbiome and virome data. Open-IBD will deliver a step-change in our ability to build robust therapeutic hypotheses and identify biomarkers for inflammatory bowel disease (IBD; encompassing Crohn’s disease (CD) and ulcerative colitis (UC)) susceptibility and progression. We will collect whole blood and stool samples at diagnosis, month 3, 6, 9, 12, 18 and 24, alongside gut biopsies at diagnosis and month 12 at colonoscopy or flexible sigmoidoscopy. By collecting outcome and disease progression data of these patients for up to four years we will: Provide a deep multi-omic characterisation of early-stage IBD (approximately 1:1 CD:UC) in a large cohort of 1,000 newly diagnosed patients. Identify molecular, cellular, bacterial and viral biomarkers of long-term outcomes in IBD, including disease progression and drug response. Nominate causal factors driving IBD pathology, including in individuals with progressive disease that is difficult to manage using existing therapies.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008470","title":"Genomic and fragmentomic landscapes of cell-free DNA in aging and disease","description":"Genome-wide analyses of cell-free DNA (cfDNA) are beginning to be used for non-invasive disease diagnosis, but these approaches have not been explored for detection of aging-related diseases.  We used low coverage whole genome sequencing (1-2x) to assess variation in cfDNA fragmentomes across 1446 individuals of varying ages with different comorbidities and genetic risk profiles. Analysis of cfDNA fragment characteristics revealed changes in overall concentration and size distributions, as well as alterations in genome-wide fragmentation profiles, chromosomal representation, repeat element landscapes, end-positions, and coverage at epigenetic regions in the circulation of aging individuals. cfDNA fragmentome characteristics were uniquely altered in a variety of human morbidities, including vascular, neurologic, and inflammatory diseases, and were independent predictors of patient outcomes in separate prospectively collected discovery (n=570) and validation (n=231) cohorts. cfDNA fragmentome-based analyses detected Alzheimer’s disease in aging individuals with varying germline risk profiles (n=645). These results identify changes in cfDNA fragmentomes in aging populations and highlight the potential of cfDNA liquid biopsies to provide snapshots of an individual’s physiologic state in health and disease.","abstract":"Genome-wide analyses of cell-free DNA (cfDNA) are beginning to be used for non-invasive disease diagnosis, but these approaches have not been explored for detection of aging-related diseases.  We used low coverage whole genome sequencing (1-2x) to assess variation in cfDNA fragmentomes across 1446 individuals of varying ages with different comorbidities and genetic risk profiles. Analysis of cfDNA fragment characteristics revealed changes in overall concentration and size distributions, as well as alterations in genome-wide fragmentation profiles, chromosomal representation, repeat element landscapes, end-positions, and coverage at epigenetic regions in the circulation of aging individuals. cfDNA fragmentome characteristics were uniquely altered in a variety of human morbidities, including vascular, neurologic, and inflammatory diseases, and were independent predictors of patient outcomes in separate prospectively collected discovery (n=570) and validation (n=231) cohorts. cfDNA fragmentome-based analyses detected Alzheimer’s disease in aging individuals with varying germline risk profiles (n=645). These results identify changes in cfDNA fragmentomes in aging populations and highlight the potential of cfDNA liquid biopsies to provide snapshots of an individual’s physiologic state in health and disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-06-19T09:16:29+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008471","title":"High clinical utility of comprehensive multi-omic molecular profiling of rare and hard-to-diagnose pediatric tumors","description":"The role of comprehensive genomic profiling for therapeutic decision-making is established in high-risk pediatric cancers, but its utility in rare and diagnostically challenging tumors is unclear. Here we report 123 non-high-risk patients enrolled in the Australian ZERO Childhood Cancer Program for diagnostic uncertainty, clinician request to address a specific molecular query, or other rare tumors. Comprehensive multi-omic profiling led to a change in diagnosis in 17.9% (22/123) of patients, with overall diagnostic utility in 35% (43/123). Molecular queries were resolved in 97.6% (40/41). Multi-omic results informed conventional management in 20.3% (25/123). Precision-guided therapy was recommended in 67.5% (83/123), and administered in 36.1% (30/83), with an objective response or prolonged (&gt;6 months) stable disease in 88.9% of evaluable cases (16/18). Findings were confirmed in an independent cohort from the Canadian KiCS program (n=41). In conclusion, in rare and diagnostically challenging pediatric tumors, multi-omic profiling improved diagnostic accuracy and informed clinical management, supporting its integration into routine care.","abstract":"The role of comprehensive genomic profiling for therapeutic decision-making is established in high-risk pediatric cancers, but its utility in rare and diagnostically challenging tumors is unclear. Here we report 123 non-high-risk patients enrolled in the Australian ZERO Childhood Cancer Program for diagnostic uncertainty, clinician request to address a specific molecular query, or other rare tumors. Comprehensive multi-omic profiling led to a change in diagnosis in 17.9% (22/123) of patients, with overall diagnostic utility in 35% (43/123). Molecular queries were resolved in 97.6% (40/41). Multi-omic results informed conventional management in 20.3% (25/123). Precision-guided therapy was recommended in 67.5% (83/123), and administered in 36.1% (30/83), with an objective response or prolonged (&gt;6 months) stable disease in 88.9% of evaluable cases (16/18). Findings were confirmed in an independent cohort from the Canadian KiCS program (n=41). In conclusion, in rare and diagnostically challenging pediatric tumors, multi-omic profiling improved diagnostic accuracy and informed clinical management, supporting its integration into routine care.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-06-20T09:38:35+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008472","title":"Expanding the utility of transcriptome analysis for mutation detection in high-risk childhood precision oncology","description":"In precision oncology, rapid and comprehensive mutation detection is essential for diagnosis, prognosis and treatment. Whole transcriptome sequencing (RNA-seq) offers unique advantages by capturing functional consequences of genomic alterations and has the potential to detect not only oncogenic fusions, but also a broad spectrum of clinically relevant mutations traditionally identified from DNA-based approaches.\nWe evaluated the utility of RNA-seq in a cohort of 477 high-risk paediatric tumours enrolled in the ZERO childhood cancer precision medicine programme with matched WGS data. A combination of reference-guided and reference-free RNA-seq algorithms were used to detect and interpret fusions and intragenic structural variants (SVs), resolving events from complex rearrangements and paralogous loci. \nRNA-seq detected 95% of gene fusions, including 33 missed by WGS. All intragenic SVs (100%) detected by WGS were also identified by RNA-seq and RNA-seq was essential for identification and/or interpretation of 30% of SVs. Additional functional insight such as aberrant splice-junctions and transcript abundance were critical for resolving pathogenicity. For single nucleotide variants and small insertions/deletions (SNVs/Indels), RNA-seq confirmed 92% and was essential for refining pathogenicity in 22% through allele-specific expression and splice assessment. These findings highlight RNA-seq as a critical complement to WGS, that transforms interpretation by adding functional context, thereby elevating diagnostic confidence and clinical decision-making.","abstract":"In precision oncology, rapid and comprehensive mutation detection is essential for diagnosis, prognosis and treatment. Whole transcriptome sequencing (RNA-seq) offers unique advantages by capturing functional consequences of genomic alterations and has the potential to detect not only oncogenic fusions, but also a broad spectrum of clinically relevant mutations traditionally identified from DNA-based approaches.\nWe evaluated the utility of RNA-seq in a cohort of 477 high-risk paediatric tumours enrolled in the ZERO childhood cancer precision medicine programme with matched WGS data. A combination of reference-guided and reference-free RNA-seq algorithms were used to detect and interpret fusions and intragenic structural variants (SVs), resolving events from complex rearrangements and paralogous loci. \nRNA-seq detected 95% of gene fusions, including 33 missed by WGS. All intragenic SVs (100%) detected by WGS were also identified by RNA-seq and RNA-seq was essential for identification and/or interpretation of 30% of SVs. Additional functional insight such as aberrant splice-junctions and transcript abundance were critical for resolving pathogenicity. For single nucleotide variants and small insertions/deletions (SNVs/Indels), RNA-seq confirmed 92% and was essential for refining pathogenicity in 22% through allele-specific expression and splice assessment. These findings highlight RNA-seq as a critical complement to WGS, that transforms interpretation by adding functional context, thereby elevating diagnostic confidence and clinical decision-making.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-06-21T23:24:07+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008473","title":"CG_Reproductive_A_MV_EndoDA_DNA_Vento_Managed","description":"A collaborative multi-institute project, using single cell atlasing and spatial techniques on endometrium samples and endometriosis cases to investigate endometriosis disease mechanisms, and endometrial cell biology (DA = 20/0002-50 BRNO).","abstract":"A collaborative multi-institute project, using single cell atlasing and spatial techniques on endometrium samples and endometriosis cases to investigate endometriosis disease mechanisms, and endometrial cell biology (DA = 20/0002-50 BRNO).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008474","title":"OAC Operable Cohorts RNASeq Tumour Tissue","description":null,"abstract":"Please see our related publication, 'Tumour DNA methylation subtypes and expression levels of CFISH (CXCL8, FCN1, IFI30, SLC11A1, HLA-DRA) predict response and overall survival to immunochemotherapy.'","study_type":"RNASeq","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008475","title":"PTA_IBD__DNA_","description":"Exploring the somatic mutations in single cells derived from inflammatory bowel disease.","abstract":"Exploring the somatic mutations in single cells derived from inflammatory bowel disease.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008476","title":"PTA_IBD__RNA_","description":"Exploring the transcriptome in single cells derived from inflammatory bowel disease.","abstract":"Exploring the transcriptome in single cells derived from inflammatory bowel disease.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008477","title":"Reference methylomes of endometrial and ectocervical epithelium","description":"Cellular heterogeneity complicates interpretation of DNA methylation biomarkers in cervicovaginal samples. We generated reference methylomes to identify markers specific to endometrial- and ectocervical epithelium-derived cells.","abstract":"Cellular heterogeneity complicates interpretation of DNA methylation biomarkers in cervicovaginal samples. We generated reference methylomes to identify markers specific to endometrial- and ectocervical epithelium-derived cells.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008478","title":"Genome-wide copy number analysis of pleural mesothelioma","description":"Genome-wide copy number analyses of treatment-naive tumors from 42 pleural mesothelioma patients were performed using the OncoScan CNV Assay for FFPE samples. The study cohort comprised nine sarcomatoid and 33 epithelioid pleural mesothelioma.","abstract":"Genome-wide copy number analyses of treatment-naive tumors from 42 pleural mesothelioma patients were performed using the OncoScan CNV Assay for FFPE samples. The study cohort comprised nine sarcomatoid and 33 epithelioid pleural mesothelioma.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008479","title":"Southern African pangenome assembly framework","description":"Constructing pangenome references to capture missing genomic variation is gaining momentum. Representing the greatest genetic diversity, Khoe-San genomes have much to contribute. Using high-fidelity pangenome technologies, we build reference-grade assemblies for three Khoe-San and two comparative European genomes (per-base accuracy 99.999%). Venn diagrams of pangenome inference using 44 public drafts and known Khoe-San variance reveals ~900,000 additional passed variants per assembled Khoe-San genome. Through Khoe-San Minigraph-Cactus alignment with public data, we identified 545,766 additional variants (GQ &gt; 50) in 66 short read derived Khoe-San genomes, with principal component confirmed clade separation. Besides pathogenic potential, among 1,837 protein-truncating variants, multigene networks central to\nolfaction and keratin functions appear significantly affected (FDR &lt; 0.022), with their phylogenetic patterns and likely long-read methylation, suggesting distinct Khoe-San evolutionary trajectories. Ultimately, establishing globally representative, genetically diverse reference resources will improve the discovery of clinically important population-specific variation for genomic medicine and evolutionary studies.","abstract":"Constructing pangenome references to capture missing genomic variation is gaining momentum. Representing the greatest genetic diversity, Khoe-San genomes have much to contribute. Using high-fidelity pangenome technologies, we build reference-grade assemblies for three Khoe-San and two comparative European genomes (per-base accuracy 99.999%). Venn diagrams of pangenome inference using 44 public drafts and known Khoe-San variance reveals ~900,000 additional passed variants per assembled Khoe-San genome. Through Khoe-San Minigraph-Cactus alignment with public data, we identified 545,766 additional variants (GQ &gt; 50) in 66 short read derived Khoe-San genomes, with principal component confirmed clade separation. Besides pathogenic potential, among 1,837 protein-truncating variants, multigene networks central to\nolfaction and keratin functions appear significantly affected (FDR &lt; 0.022), with their phylogenetic patterns and likely long-read methylation, suggesting distinct Khoe-San evolutionary trajectories. Ultimately, establishing globally representative, genetically diverse reference resources will improve the discovery of clinically important population-specific variation for genomic medicine and evolutionary studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008480","title":"ACED__Targeted_NanoSeq_for_deep_subclonal_selection_in_the_normal_kidney","description":"Targeted NanoSeq of normal kidney samples to characterise their deep subclonal landscape and patterns of selection. ","abstract":"This study will use Targeted NanoSeq of the normal kidney to characterise their deep subclonal landscape and patterns of selection.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008481","title":"NK_CD8_CRISPR_screens","description":"Human CD8 and NK cells are isolated from peripheral blood and transduced with bespoke CRISPR libraries to KO genes. These cells are expanded and then exposed to different conditions prior to stimulation and phenotypic sorting.","abstract":"Human CD8 and NK cells are isolated from peripheral blood and transduced with bespoke CRISPR libraries to KO genes. These cells are expanded and then exposed to different conditions prior to stimulation and phenotypic sorting. Genomic DNA is enriched for gRNA containing sequences which have Illumina adapters added and UDI tags. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008482","title":"Genome-wide association study of 3,087 patients with severe COVID-19 in the Japanese population","description":"The Japan COVID-19 Task Force (JCTF) is a nationwide cohort established to investigate the clinical and genetic characteristics of patients with COVID-19 in Japan. JCTF has enrolled more than 6,000 patients with COVID-19. In this study, we performed a genome-wide association study of 3,087 patients with severe COVID-19 and 55,896 population controls from Biobank Japan. We characterized structural haplotypes tagged by the GWAS lead variant.","abstract":"The Japan COVID-19 Task Force (JCTF) is a nationwide cohort established to investigate the clinical and genetic characteristics of patients with COVID-19 in Japan. JCTF has enrolled more than 6,000 patients with COVID-19. In this study, we performed a genome-wide association study of 3,087 patients with severe COVID-19 and 55,896 population controls from Biobank Japan. We characterized structural haplotypes tagged by the GWAS lead variant.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008483","title":"CG_Liver_A_King_s_Liver_Research_Biobank_Xenium_Lotfollahi_Managed","description":"Somatic mutations in normal and diseased hepatopancreaticobiliary tissues","abstract":"Characterise the somatic mutations in normal and diseased tissues and identify genomic biomarkers and mutational signatures in health and disease","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008484","title":"Single_cell_eQTL_mapping_of_immune_response_regulation_in_systemic_lupus_erythematosus_patients","description":"Systemic lupus erythematosus (SLE) is a complex, multisystem autoimmune disease driven by cell-type-specific regulatory networks. Single-cell expression quantitative trait locus (sc-eQTL) mapping provides a powerful approach to uncover how genetic variation influences immune cell function and transcriptional responses in SLE. 300 SLE patients from multiple ancestries and 11 healthy controls were recruited from two sites in London. We generated whole genome sequencing data and single cell gene expression (scRNA-seq), surface protein (CITE-seq) and B/T cell receptor (BCR/TCR) data from peripheral blood mononuclear cells. \n\nDNA library pools were sequenced using the Illumina NovaSeq6000 S4 platform, with 150-bp paired-end reads, aiming for 15x depth. Single cell data was generated using 10X Genomics Chromium platform with samples were multiplexed into 69 pools, each containing four to five samples. RNA, CITE, TCR, and BCR libraries were sequenced at a 10:1:1:1 ratio, respectively, using the Illumina NovaSeq6000 S4, with 100-bp paired-end reads. Pooled samples were demultiplexed using genotypes from whole genome sequencing data.","abstract":"Systemic lupus erythematosus (SLE) is a complex, multisystem autoimmune disease driven by cell-type-specific regulatory networks. Single-cell expression quantitative trait locus (sc-eQTL) mapping provides a powerful approach to uncover how genetic variation influences immune cell function and transcriptional responses in SLE. 300 SLE patients from multiple ancestries and 11 healthy controls were recruited from two sites in London. We generated whole genome sequencing data and single cell gene expression (scRNA-seq), surface protein (CITE-seq) and B/T cell receptor (BCR/TCR) data from peripheral blood mononuclear cells. \n\nDNA library pools were sequenced using the Illumina NovaSeq6000 S4 platform, with 150-bp paired-end reads, aiming for 15x depth. Single cell data was generated using 10X Genomics Chromium platform with samples were multiplexed into 69 pools, each containing four to five samples. RNA, CITE, TCR, and BCR libraries were sequenced at a 10:1:1:1 ratio, respectively, using the Illumina NovaSeq6000 S4, with 100-bp paired-end reads. Pooled samples were demultiplexed using genotypes from whole genome sequencing data.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008485","title":"Oncofusion-driven transcription unlocks a multilayered neoprotein landscape in Ewing sarcoma","description":null,"abstract":"Cancer-driving chromosomal translocations are primarily defined by the downstream cellular pathways they modulate to promote a malignant phenotype. In Ewing sarcoma (EwS), the chimeric EWSR1::ETS gene fusion proteins (primarily EWSR1::FLI1) extend this paradigm by systematically repurposing otherwise silent or “dark” genomic sequences to produce tumor-specific transcripts, termed neogenes. Here, we explore the EwS dark proteome by integrating long-read transcriptomes, (single-cell) translatomes, proteomes, and immunopeptidomes. We uncover thousands of EwS-specific transcript isoforms within 252 canonical genes, termed neoisoforms, impacting 12 core cellular pathways and key EwS genes including NKX2-2. Neoisoforms are recurrently translated across 48 patient tumors, with neoprotein synthesis rates exceeding those of traditional proteins. Neoisoforms give rise to 44 frameshifted neoproteins, a subset of which we validate as tumor-restricted by immunofluorescence microscopy and HLA-I immunopeptidomics, demonstrating endogenous neoprotein expression, localization, and antigen presentation. The EwS defining neoprotein with highest cancer-restricted expression is the 80-aa TRPM4-dORF, which could be detected in 27 out of 47 patient tumor proteomes, independently across 4 different proteomics datasets, and with 5 unique peptides. Mechanistically, TRPM4-dORF is translated from the 3'UTR of a canonical transcript through polyA readthrough, a phenomenon we find enriched among EwS neoisoform-bearing genes, suggesting that fusion-driven transcriptional rewiring may also alter translational fidelity at canonical loci. Collectively, our findings reframe oncofusion biology: EWSR1::ETS continuously induces transcription of novel translatable sequences, creating a repertoire of tumor-restricted neoproteins hidden in the so-called dark proteome that can be presented by HLA-I, revealing a new class of intracellular EwS-specific antigens with immunotherapeutic potential.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008486","title":"Whole-blood RNA-seq in AtezoBev-treated HCC","description":"This dataset contains RNA-sequencing BAM files generated from paired whole-blood RNA samples collected from patients with advanced hepatocellular carcinoma treated with first-line atezolizumab–bevacizumab immunotherapy. Samples were collected at baseline before the first infusion (T0) and immediately prior to the second infusion (T1). The dataset includes paired longitudinal samples from 24 patients, comprising 13 responders and 11 progressors. RNA sequencing was performed by Novogene using a GlobinClear-based non-directional mRNA library preparation strategy. These data support transcriptomic analyses of circulating immune activation, treatment response and resistance mechanisms under atezolizumab–bevacizumab therapy.\n","abstract":"This dataset contains RNA-sequencing BAM files generated from paired whole-blood RNA samples collected from patients with advanced hepatocellular carcinoma treated with first-line atezolizumab–bevacizumab immunotherapy. Samples were collected at baseline before the first infusion (T0) and immediately prior to the second infusion (T1). The dataset includes paired longitudinal samples from 24 patients, comprising 13 responders and 11 progressors. RNA sequencing was performed by Novogene using a GlobinClear-based non-directional mRNA library preparation strategy. These data support transcriptomic analyses of circulating immune activation, treatment response and resistance mechanisms under atezolizumab–bevacizumab therapy.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-07-03T14:03:46+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008487","title":"Targeted_EMSeq___Arthritis","description":"Targeted EMSeq of arthritis samples","abstract":"Targeted EMSeq of arthritis samples","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008488","title":"Targeted_EMSeq___Cancer_Predisposition___LFS","description":"Targeted EMSeq of cancer predisposition samples (Li-Fraumeni syndrome)","abstract":"Targeted EMSeq of cancer predisposition samples (Li-Fraumeni syndrome)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008489","title":"Targeted_EMSeq___Cancer_Predisposition___PTEN","description":"Targeted EMSeq of cancer predisposition samples (PTEN syndrome)","abstract":"Targeted EMSeq of cancer predisposition samples (PTEN syndrome)","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008490","title":"Targeted_EMSeq___Paediatric_IBD","description":"Targeted EMSeq of paediatric IBD samples","abstract":"Targeted EMSeq of paediatric IBD samples","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008491","title":"Targeted_EMSeq___Pleura","description":"Targeted EMSeq of pleural samples","abstract":"Targeted EMSeq of pleural samples","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008492","title":"Targeted_EMSeq___PSC_and_PBC","description":"Targeted EMSeq of PSC and PBC samples","abstract":"Targeted EMSeq of PSC and PBC samples","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008493","title":"Targeted_EMSeq___Skin_immune","description":"Targeted EMSeq of skin immune samples","abstract":"Targeted EMSeq of skin immune samples","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008494","title":"Preclinical trial supports dual inhibition of BCL2 and aurora kinase for MYCN-amplified high-risk neuroblastoma","description":"Half of all children with high-risk neuroblastoma experience relapse or have refractory disease. These children lack effective options, and few survive beyond 5 years. The BCL2 inhibitor venetoclax, combined with cyclophosphamide/topotecan, has clinical activity in relapsed and refractory neuroblastoma, however with severe treatment-emergent adverse events. Combination drug screening in patient-derived models identified approved drugs synergistic with venetoclax, including the aurora kinase inhibitor alisertib. We assessed venetoclax-alisertib in 22 diverse neuroblastoma PDX models using an n=1 clinical trial-like design. Venetoclax-alisertib induced objective response in all models but was particularly effective in models of MYCN-amplified disease (n=12), doubling median survival time compared to cyclophosphamide/topotecan, and outperforming venetoclax/cyclophosphamide/topotecan. The efficacy of venetoclax-alisertib was maintained with discontinuous schedules, minimizing hematological toxicity without substantially compromising activity. Venetoclax-alisertib was strikingly effective with anti-GD2 immunotherapy, allowing long-term survival of PDX-engrafted animals. Our findings support advancement of venetoclax-alisertib to clinical trial for neuroblastoma with or without anti-GD2 immunotherapy.","abstract":"Half of all children with high-risk neuroblastoma experience relapse or have refractory disease. These children lack effective options, and few survive beyond 5 years. The BCL2 inhibitor venetoclax, combined with cyclophosphamide/topotecan, has clinical activity in relapsed and refractory neuroblastoma, however with severe treatment-emergent adverse events. Combination drug screening in patient-derived models identified approved drugs synergistic with venetoclax, including the aurora kinase inhibitor alisertib. We assessed venetoclax-alisertib in 22 diverse neuroblastoma PDX models using an n=1 clinical trial-like design. Venetoclax-alisertib induced objective response in all models but was particularly effective in models of MYCN-amplified disease (n=12), doubling median survival time compared to cyclophosphamide/topotecan, and outperforming venetoclax/cyclophosphamide/topotecan. The efficacy of venetoclax-alisertib was maintained with discontinuous schedules, minimizing hematological toxicity without substantially compromising activity. Venetoclax-alisertib was strikingly effective with anti-GD2 immunotherapy, allowing long-term survival of PDX-engrafted animals. Our findings support advancement of venetoclax-alisertib to clinical trial for neuroblastoma with or without anti-GD2 immunotherapy.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-07-08T06:41:24+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008495","title":"Contains long-read whole transcriptome (cDNA-PCR) fastq data for 9 human post-mortem brain samples. Reads were generated using Oxford Nanopore Technologies PromethION flow cells.","description":"Quantifying the diversity of RNAs and proteins produced by cells is fundamental to the biological and clinical sciences. However, many RNAs and proteins remain uncharacterised, especially proteins translated from alternate RNA isoforms; untranslated regions and non-coding RNAs (ncRNAs), as well as the effects of DNA variation on protein sequences. Proteogenomics aims to characterize the complete proteome by integrating genomics and transcriptomics with proteomics but current tools have limitations in useability, analysis features and visualization of resulting data. To address these gaps, we developed GenomeProt, a user-friendly GUI-based tool for integrative proteogenomic analysis. We demonstrate its utility by integrating long-read RNA sequencing with mass-spectrometry-based proteomics to pinpoint proteoform expression generated by alternative splicing; discover potential novel, unannotated proteins in human brain samples (data are available via ProteomeXchange with identifier PXD080085); and quantify variant-containing peptides associated with treatment resistance in a melanoma xenograft model. GenomeProt brings the discovery power of proteogenomics to biologists, illuminating the hidden proteome.","abstract":"Quantifying the diversity of RNAs and proteins produced by cells is fundamental to the biological and clinical sciences. However, many RNAs and proteins remain uncharacterised, especially proteins translated from alternate RNA isoforms; untranslated regions and non-coding RNAs (ncRNAs), as well as the effects of DNA variation on protein sequences. Proteogenomics aims to characterize the complete proteome by integrating genomics and transcriptomics with proteomics but current tools have limitations in useability, analysis features and visualization of resulting data. To address these gaps, we developed GenomeProt, a user-friendly GUI-based tool for integrative proteogenomic analysis. We demonstrate its utility by integrating long-read RNA sequencing with mass-spectrometry-based proteomics to pinpoint proteoform expression generated by alternative splicing; discover potential novel, unannotated proteins in human brain samples (data are available via ProteomeXchange with identifier PXD080085); and quantify variant-containing peptides associated with treatment resistance in a melanoma xenograft model. GenomeProt brings the discovery power of proteogenomics to biologists, illuminating the hidden proteome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008496","title":"The Landscape of Chromosomal Instability in Pediatric Solid Tumors","description":null,"abstract":"\"Chromosomal instability (CIN) is characterized by ongoing structural and numerical chromosomal alterations. Recently, seventeen recurrent copy number signatures have been defined based on TCGA data, capturing distinct CIN processes in adult cancers. These CIN signatures can be used to predict disease aggressiveness and therapeutic resistance. However, the prevalence and characteristics of CIN in pediatric cancers remains largely unexplored. This limits insights into the underlying mechanisms and therapeutic potential of CIN in pediatric cancers.\n\nWe applied this CIN signature detection framework to whole-genome sequencing data generated from 312 pediatric solid tumors. CIN was detected in 68% of the tumors and de novo CIN signature extraction identified nine of the 17 TCGA CIN signatures in these pediatric CIN tumors. We highlight the most active CIN signatures in pediatric CIN tumors are characterized by impaired homologous recombination (IHR), replication stress, and high-level amplifications. Moreover, mutational analysis of the 376 putative CIN-related genes in pediatric CIN tumors revealed four genes (COPS3, ALKBH5, UBB and TP53) associated with the highest activity of IHR with replication-stress induced CIN. This CIN signature activity was further increased in pediatric CIN tumors with both TP53 mutations and whole-genome duplication (WGD). Lastly, complex structural variant (CSV) analysis revealed that 67% of the CIN tumors contain at least one CSV. These CIN tumors with CSVs demonstrated the highest activity in structural CIN signatures including IHR, replication stress and amplifications.\n\nWe present CIN signature analysis carried out in pediatric cancer and demonstrate a high prevalence of pediatric CIN as well as distinct mechanistic CIN etiologies. Pediatric CIN tumors are defined by a combination of CIN-related gene mutations, whole genome duplication events and complex structural variants that collectively increase CIN activity. Our findings capture the distinct landscape of CIN in pediatric solid tumors and reveal CIN signatures with actionable targets for potential future therapeutic intervention.\"","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008497","title":"Single-cell profiling of peripheral blood from treatment-naïve GBM patients and healthy donors.","description":"Glioblastoma (GBM) induces systemic immune reprogramming characterized by altered circulating myeloid and lymphoid populations. Single-cell profiling of peripheral blood from treatment-naïve GBM patients identified heterogeneous monocyte states, expansion of suppressive myeloid cells, reduced MHC class II expression and distinct GBM-associated immune signatures. These findings support peripheral blood immune profiling as a potential source of biomarkers in GBM.","abstract":"Glioblastoma (GBM) induces systemic immune reprogramming characterized by altered circulating myeloid and lymphoid populations. Single-cell profiling of peripheral blood from treatment-naïve GBM patients identified heterogeneous monocyte states, expansion of suppressive myeloid cells, reduced MHC class II expression and distinct GBM-associated immune signatures. These findings support peripheral blood immune profiling as a potential source of biomarkers in GBM.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-08-17T15:22:19.151008+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008498","title":"CG_Tongue_P_BW_BulkRNA_Behjati_Managed","description":"Beckwith-Wiedemann syndrome (BWS) is a congenital disorder associated with overgrowth and predisposition to certain cancers, caused by abnormalities in the methylation of regulatory regions on chr11p. Patients often present with hemi-hypertrophy, i.e., overgrowth of certain body parts, such as the tongue, only on one side of their body. Tongue resection surgery is often done to improve patients’ life quality. In this study, we perform multimodal sequencing of resected tongues to compare the overgrown and non-overgrown sides to understand why the phenotype is seen only on one side of the body. By comparing the left and right side of the body, we can understand the lineage relationships of cells with alterations in chr11p methylation and the transcriptional consequences of those changes depending on the context (overgrown vs non-overgrown side).","abstract":"Beckwith-Wiedemann syndrome (BWS) is a congenital disorder associated with overgrowth and predisposition to certain cancers, caused by abnormalities in the methylation of regulatory regions on chr11p. Patients often present with hemi-hypertrophy, i.e., overgrowth of certain body parts, such as the tongue, only on one side of their body. Tongue resection surgery is often done to improve patients’ life quality. In this study, we perform multimodal sequencing of resected tongues to compare the overgrown and non-overgrown sides to understand why the phenotype is seen only on one side of the body. By comparing the left and right side of the body, we can understand the lineage relationships of cells with alterations in chr11p methylation and the transcriptional consequences of those changes depending on the context (overgrown vs non-overgrown side).","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008499","title":"CG_Tongue_P_BW_WGS_Behjati_Managed","description":"Beckwith-Wiedemann syndrome (BWS) is a congenital disorder associated with overgrowth and predisposition to certain cancers, caused by abnormalities in the methylation of regulatory regions on chr11p. Patients often present with hemi-hypertrophy, i.e., overgrowth of certain body parts, such as the tongue, only on one side of their body. Tongue resection surgery is often done to improve patients’ life quality. In this study, we perform multimodal sequencing of resected tongues to compare the overgrown and non-overgrown sides to understand why the phenotype is seen only on one side of the body. By comparing the left and right side of the body, we can understand the lineage relationships of cells with alterations in chr11p methylation and the transcriptional consequences of those changes depending on the context (overgrown vs non-overgrown side).","abstract":"Beckwith-Wiedemann syndrome (BWS) is a congenital disorder associated with overgrowth and predisposition to certain cancers, caused by abnormalities in the methylation of regulatory regions on chr11p. Patients often present with hemi-hypertrophy, i.e., overgrowth of certain body parts, such as the tongue, only on one side of their body. Tongue resection surgery is often done to improve patients’ life quality. In this study, we perform multimodal sequencing of resected tongues to compare the overgrown and non-overgrown sides to understand why the phenotype is seen only on one side of the body. By comparing the left and right side of the body, we can understand the lineage relationships of cells with alterations in chr11p methylation and the transcriptional consequences of those changes depending on the context (overgrown vs non-overgrown side).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008500","title":"OPEN_IBD_Metagenomics","description":"Open-IBD, a longitudinal multi-omics inception cohort in IBD. Studying the biology of IBD from the point of diagnosis, without the confounders of time, uncontrolled inflammation and exposure to multiple therapies, provides an unparalleled opportunity for deriving biomarkers and mechanistic insights that aid the discovery and validation of therapeutic targets in IBD. 1000 confirmed newly diagnosed IBD patients will be sampled to collect intestinal biopsies at diagnosis and after one year from diagnosis. Blood and stool samples will be also collected at diagnosis and  months 3, 6, 9, 12, 18 and 24 after. DNA will be extracted from buffered preserved stools samples to generate metagenomic shotgun sequencing data from 3800 samples covering IBD baseline (1000) and 12 month follow ups samples (1000) and targeted IBD samples due to clinical scenarios of interest (1400) : disease progression/ presurgery samples/ samples previous and post treatment to advanced therapies. Additionally, metagenomics data will also be generated from non IBD stool samples collected at diagnosis time (400).","abstract":"Open-IBD, a longitudinal multi-omics inception cohort in IBD. Studying the biology of IBD from the point of diagnosis, without the confounders of time, uncontrolled inflammation and exposure to multiple therapies, provides an unparalleled opportunity for deriving biomarkers and mechanistic insights that aid the discovery and validation of therapeutic targets in IBD. 1000 confirmed newly diagnosed IBD patients will be sampled to collect intestinal biopsies at diagnosis and after one year from diagnosis. Blood and stool samples will be also collected at diagnosis and  months 3, 6, 9, 12, 18 and 24 after. DNA will be extracted from buffered preserved stools samples to generate metagenomic shotgun sequencing data from 3800 samples covering IBD baseline (1000) and 12 month follow ups samples (1000) and targeted IBD samples due to clinical scenarios of interest (1400) : disease progression/ presurgery samples/ samples previous and post treatment to advanced therapies. Additionally, metagenomics data will also be generated from non IBD stool samples collected at diagnosis time (400).","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008501","title":"Longuitudinal_scRNAseq_of_UC_cohort","description":"The diagnosis of anti–interleukin-10 positivity in patients with IBD may have implications for clinical decision making. There has been reported that presence of anti-IL 10 autoantibodies is associated to higher susceptibility risk for severe phenotypes of IBD. \n\nTo investigate this association, we collected samples ( blood and gut biopsies) from Ulcerative colitis patients with presence of anti-IL10 autoantibodies in serum before and after B cell depletion treatment to investigate this biological mechanism at single cell resolution. ","abstract":"The diagnosis of anti–interleukin-10 positivity in patients with IBD may have implications for clinical decision making. There has been reported that presence of anti-IL 10 autoantibodies is associated to higher susceptibility risk for severe phenotypes of IBD. \n\nTo investigate this association, we collected samples ( blood and gut biopsies) from Ulcerative colitis patients with presence of anti-IL10 autoantibodies in serum before and after B cell depletion treatment to investigate this biological mechanism at single cell resolution.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008502","title":"Tucan: Ultra-fast Methylation-based Classifier for pediatric solid tumors and lymphomas ","description":null,"abstract":"The high heterogeneity of pediatric cancers presents significant diagnostic challenges, underscoring the need for accurate classification. Although molecular profiling supports first-line diagnostics and guides treatment, it can delay final diagnosis.  While Nanopore-based methylation analysis has enabled rapid CNS tumor diagnosis, its application to pediatric solid tumors and lymphomas has remained largely unexplored. We developed Tucan, a classifier trained on 3,818 methylation array profiles representing 84 subtypes, designed to classify tumors from sparse Nanopore methylation data. In retrospective validation (n=514), Tucan generated confident predictions (CFT $\\geq$ 0.7) within 30 minutes of sequencing in 385 cases, achieving 372 correct diagnoses (F1-score: 0.98). In prospective testing (n=74; 63 classifiable), 52 samples reached the confidence threshold with 96\\% accuracy, confirming the original diagnosis in 47 cases and correctly refining or revising it in three. Together, Tucan enables rapid, high-confidence molecular classification of pediatric solid tumors and lymphomas.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008503","title":"Multi-omic dissection of molecular divergence underlying differential immune responses in Crohn's disease and ulcerative colitis","description":null,"abstract":"This study investigates molecular divergence underlying differential immune responses in Crohn's disease and ulcerative colitis using single-nucleus multiome profiling and immune stimulation data. This submission contains encrypted raw 10x Genomics single-cell multiome FASTQ files from batch 2 pooled PBMC libraries IBD1 and IBD2, including gene expression and chromatin accessibility libraries.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008504","title":"Investigating the host and pathogen interaction of TB disease","description":"This study sought to understand how TB patients interact with the infecting Mycobacterium tuberculosis lineage","abstract":"This study sought to understand how TB patients interact with the infecting Mycobacterium tuberculosis lineage","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008505","title":"Long-read whole-genome sequencing of ATLL","description":"Long-read whole-genome sequencing of three adult T-cell leukemia/lymphoma (ATLL) samples using PacBio Revio.","abstract":"Long-read whole-genome sequencing of three adult T-cell leukemia/lymphoma (ATLL) samples using PacBio Revio.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008506","title":"WGS_and_SNP_Characterization_of_Bladder_Cancer_Organoids","description":"Characterization of 6 patient-derived bladder cancer organoids by WGS and SNP analysis for later authentication. The organoids are originally derived by Colombia University and have been obtained by Sanger with associated HuMFre 25/0019. We would like to run SGP supported algorithms including Caveman, Pindel and Ascat for variant calling.","abstract":"Characterization of 6 patient-derived bladder cancer organoids by WGS and SNP analysis for later authentication.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008507","title":"CG_Tongue_P_BW_LongRead_Behjati_Managed","description":"Beckwith-Wiedemann syndrome (BWS) is a congenital disorder associated with overgrowth and predisposition to certain cancers, caused by abnormalities in the methylation of regulatory regions on chr11p. Patients often present with hemi-hypertrophy, i.e., overgrowth of certain body parts, such as the tongue, only on one side of their body. Tongue resection surgery is often done to improve patients’ life quality. In this study, we perform multimodal sequencing of resected tongues to compare the overgrown and non-overgrown sides to understand why the phenotype is seen only on one side of the body. By comparing the left and right side of the body, we can understand the lineage relationships of cells with alterations in chr11p methylation and the transcriptional consequences of those changes depending on the context (overgrown vs non-overgrown side).","abstract":"Beckwith-Wiedemann syndrome (BWS) is a congenital disorder associated with overgrowth and predisposition to certain cancers, caused by abnormalities in the methylation of regulatory regions on chr11p. Patients often present with hemi-hypertrophy, i.e., overgrowth of certain body parts, such as the tongue, only on one side of their body. Tongue resection surgery is often done to improve patients’ life quality. In this study, we perform multimodal sequencing of resected tongues to compare the overgrown and non-overgrown sides to understand why the phenotype is seen only on one side of the body. By comparing the left and right side of the body, we can understand the lineage relationships of cells with alterations in chr11p methylation and the transcriptional consequences of those changes depending on the context (overgrown vs non-overgrown side).","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008508","title":"Computational drug repurposing identifies N-acetylglucosamine as a potential therapeutic compound for CLN3 Batten disease","description":"Batten disease, also known as neuronal ceroid lipofuscinoses, is one of the most common causes of childhood dementia. It is characterized by the accumulation of lipofuscin in lysosomes, leading to loss of brain cell function, onset of dementia-like symptoms, vision loss and seizures and has extremely limited treatment options. Here, we performed computational drug repurposing analysis to identify existing compounds that may target Batten disease risk genes. A total of 81 candidate compounds were identified, 6 of which were selected based on clinical tractability for downstream testing in Batten disease (CLN3) iPSC-derived models. After confirming disease phenotype and drug candidate safety, CLN3 brain cell cultures treated with and without drug candidates underwent bulk RNA-seq to identify drug responses. One of the candidate drugs N-acetylglucosamine (GlcNAc) significantly upregulated Batten disease risk gene CLN5 expression and several other lysosomal markers within CLN3 brain cells, and modulated several pathways implicated in lysosomal storage disorders. Importantly, GlcNAc significantly reduced lipofuscin burden in both CLN3 iPSC-derived neurons and astrocytes, supporting its investigation as an additional therapy for Batten disease. ","abstract":"Batten disease, also known as neuronal ceroid lipofuscinoses, is one of the most common causes of childhood dementia. It is characterized by the accumulation of lipofuscin in lysosomes, leading to loss of brain cell function, onset of dementia-like symptoms, vision loss and seizures and has extremely limited treatment options. Here, we performed computational drug repurposing analysis to identify existing compounds that may target Batten disease risk genes. A total of 81 candidate compounds were identified, 6 of which were selected based on clinical tractability for downstream testing in Batten disease (CLN3) iPSC-derived models. After confirming disease phenotype and drug candidate safety, CLN3 brain cell cultures treated with and without drug candidates underwent bulk RNA-seq to identify drug responses. One of the candidate drugs N-acetylglucosamine (GlcNAc) significantly upregulated Batten disease risk gene CLN5 expression and several other lysosomal markers within CLN3 brain cells, and modulated several pathways implicated in lysosomal storage disorders. Importantly, GlcNAc significantly reduced lipofuscin burden in both CLN3 iPSC-derived neurons and astrocytes, supporting its investigation as an additional therapy for Batten disease. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008509","title":"HumanIslets Genomics: A multimodal resource reveals cellular-scale impact of common diabetes genetic risk","description":null,"abstract":"Discovery of common diabetes risk variants is approaching saturation, yet how largely non-coding variants converge to shape insulin secretion and dysglycemia has not been annotated at scale. Here, we establish HumanIslets Genomics, a multimodal resource linking common genetic variation in 427 post-mortem human islet donors to molecular and whole-islet cellular phenotyping. Integrating these data with existing datasets, we generate the largest genetic regulatory map of chromatin accessibility, gene expression, and protein abundance in human islets to date, colocalizing 534 genetic signals with glycemic traits and diabetes risk. We show that partitioned beta-cell diabetes polygenic risk identifies convergent cellular phenotypes not detected by whole-genome scores and stratifies islet cellular physiology and post-isolation quality traits with effects comparable to clinical and procurement covariates. Finally, we find that this risk acts through a distributed architecture, with many small effects accumulating into measurable changes in glycemic physiology. The resource is available at HumanIslets.com.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008510","title":"Tracing the spatial genomic evolution in the clonal history of follicular thyroid neoplasms","description":"Follicular thyroid neoplasms span follicular adenoma and minimally to widely invasive follicular carcinoma, a distinction made solely by capsular and/or vascular invasion on histology. To answer whether invasive potential is genomically encoded, we conducted 88 whole-genome sequencing from laser-capture microdissected micropatches, sampling non-invasive and invasive foci, and one lung metastasis from 13 follicular thyroid neoplasm patients (3 adenomas, 8 minimally invasive and 2 widely invasive carcinomas). Genomes were largely silent and endogenous in origin, with no consistent mutational difference between adenomas and carcinomas or between invasive and non-invasive regions of the same tumor. RAS status instead specified the mode of clonal evolution, which is neutral big-bang expansion in RAS-mutant tumors versus serial subclonal emergence with arm-level copy number change in RAS-wildtype tumors. And mutational timing resolved a ~3-decade lag phase preceding overt growth at ~0.6 cm/year, with an early-branching hypermutated lineage in the metastatic case. This dataset comprises somatic point mutations, copy number alterations, and rearrangements with clonal phylogenies across the adenoma–carcinoma spectrum.","abstract":"Follicular thyroid neoplasms span follicular adenoma and minimally to widely invasive follicular carcinoma, a distinction made solely by capsular and/or vascular invasion on histology. To answer whether invasive potential is genomically encoded, we conducted 88 whole-genome sequencing from laser-capture microdissected micropatches, sampling non-invasive and invasive foci, and one lung metastasis from 13 follicular thyroid neoplasm patients (3 adenomas, 8 minimally invasive and 2 widely invasive carcinomas). Genomes were largely silent and endogenous in origin, with no consistent mutational difference between adenomas and carcinomas or between invasive and non-invasive regions of the same tumor. RAS status instead specified the mode of clonal evolution, which is neutral big-bang expansion in RAS-mutant tumors versus serial subclonal emergence with arm-level copy number change in RAS-wildtype tumors. And mutational timing resolved a ~3-decade lag phase preceding overt growth at ~0.6 cm/year, with an early-branching hypermutated lineage in the metastatic case. This dataset comprises somatic point mutations, copy number alterations, and rearrangements with clonal phylogenies across the adenoma–carcinoma spectrum.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008511","title":"Cord_Blood_Colonies_WGS","description":"Whole genome sequencing to determine mutational landscape of cord blood colonies","abstract":"Whole genome sequencing to determine mutational landscape of cord blood colonies","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008512","title":"Cord_Blood_Colonies_WGMS","description":"Whole genome methylation sequencing to determine methylation landscape of cord blood colonies","abstract":"Whole genome methylation sequencing to determine methylation landscape of cord blood colonies","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008513","title":"Osteosarcoma_multiregion_characterisation___Xenium","description":"Characterisation of osteosarcoma across multiple regions of primary tumours, local recurrences and metastases using whole genome sequencing, methylation and transcriptomics. This study contains the Xenium data.","abstract":"Osteosarcoma tumours typically have highly rearranged genomes. In this study, we investigate the mechanisms driving genomic instability and formation of complex rearrangements, as well as the phenotypic impact of these alterations on tumour biology. ","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008514","title":"Whole_genome_sequencing_oesophageal_epithelium","description":"We wish to investigate copy number changes in normal human oesophageal epithelium.  ","abstract":"We wish to investigate copy number changes in normal human oesophageal epithelium.  ","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008515","title":"CG_Pancreas_A_nPOD_Biobank_T2D_Xenium_Lotfollahi_Managed","description":"Spatial Characterisation of the Human Pancreas in Type 2 Diabetes at Single Cell Resolution","abstract":"This project uses high-resolution Xenium spatial transcriptomics to characterise the cellular composition and organisation of the human pancreas in the context of type 2 diabetes (T2D). The aim is to map endocrine, exocrine, stromal, and immune cell populations within intact tissue and define their spatial relationships. We focus on identifying cell-type-specific transcriptional programs and potential cell–cell communication interactions within the pancreatic microenvironment. The data will be used to generate a spatially resolved atlas of pancreatic tissue and to support integrative analyses with complementary single-cell datasets. Overall, this work aims to provide a detailed framework for studying tissue architecture and cellular interactions relevant to T2D.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008516","title":"Genomic and Epigenomic Profiling in Brain Tumors: A Comparison of 5-Base, EPICv2, and Nanopore-sequencing","description":"This study systematically compares Illumina 5-base sequencing, Infinium EPICv2 microarrays, and Oxford Nanopore Technologies sequencing for integrated genomic and epigenomic profiling of fresh-frozen brain tumors. Using 16 samples initially diagnosed as glioblastoma, including 10 additionally analyzed by nanopore sequencing, we evaluated sequencing performance, coverage of difficult genomic regions, DNA methylation concordance, detection of somatic and copy-number alterations, and haplotype reconstruction. The results demonstrate the complementary strengths of these platforms: 5-base sequencing provides high accuracy, yield, and broad methylome coverage, while nanopore sequencing offers more uniform coverage of problematic regions and enables haplotype-resolved and allele-specific methylation analysis. Their integration may support the development of more comprehensive molecular profiling workflows for precision oncology.","abstract":"This study systematically compares Illumina 5-base sequencing, Infinium EPICv2 microarrays, and Oxford Nanopore Technologies sequencing for integrated genomic and epigenomic profiling of fresh-frozen brain tumors. Using 16 samples initially diagnosed as glioblastoma, including 10 additionally analyzed by nanopore sequencing, we evaluated sequencing performance, coverage of difficult genomic regions, DNA methylation concordance, detection of somatic and copy-number alterations, and haplotype reconstruction. The results demonstrate the complementary strengths of these platforms: 5-base sequencing provides high accuracy, yield, and broad methylome coverage, while nanopore sequencing offers more uniform coverage of problematic regions and enables haplotype-resolved and allele-specific methylation analysis. Their integration may support the development of more comprehensive molecular profiling workflows for precision oncology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008517","title":"The_Little_Princess_Knowledge_Bank_ScRNA","description":"We propose to build a genetic knowledge bank of Wilms tumour that integrates clinical outcome data with a genetic, epigenetic, and transcriptomic survey of 1,000 Wilms tumours. The purpose of the knowledge bank is to serve as a community resource and to address the following specific questions about Wilms tumour: (1) Do genetic, epigenetic, or transcriptional features predict outcome and thus lend themselves to treatment stratification? (2) What are the genetic drivers of Wilms tumour, considering the entire histological spectrum of Wilms tumour including the most common subtypes classified as intermediate risk?","abstract":"We propose to build a genetic knowledge bank of Wilms tumour that integrates clinical outcome data with a genetic, epigenetic, and transcriptomic survey of 1,000 Wilms tumours. The purpose of the knowledge bank is to serve as a community resource and to address the following specific questions about Wilms tumour: (1) Do genetic, epigenetic, or transcriptional features predict outcome and thus lend themselves to treatment stratification? (2) What are the genetic drivers of Wilms tumour, considering the entire histological spectrum of Wilms tumour including the most common subtypes classified as intermediate risk?","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008518","title":"Antigen-resolved remodeling of EBV-specific CD8⁺ T cell immunity in multiple sclerosis","description":"In this study, we use single-cell RNA and TCR sequencing to identify disease-specific transcriptional differences in CD8+ T cell control of EBV-infected B cells in MS. ","abstract":"In this study, we use single-cell RNA and TCR sequencing to identify disease-specific transcriptional differences in CD8+ T cell control of EBV-infected B cells in MS. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-08-04T01:33:56+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008519","title":"Long_read_single_sperm_whole_genome_sequencing","description":"Pilot study to establish single-cell long-read whole-genome sequencing (PacBio HiFi, ~10× per cell) of PTA-amplified single sperm and blood cells from two donors, and to characterise somatic mosaicism and clonal structure across germline and somatic lineages.","abstract":"Somatic mutations accumulate in every cell lineage throughout life, but resolving them in single cells at both base-pair and structural resolution remains technically challenging — particularly in the germline, where per-cell mutation burdens are low. Primary Template-directed Amplification (PTA) provides high-fidelity, even whole-genome amplification from single cells, and pairing it with PacBio HiFi long-read sequencing enables joint detection of single-nucleotide variants, indels, structural variants and copy-number changes, together with read-level haplotype phasing that short reads cannot provide.\nThis pilot study will establish and benchmark single-cell long-read PTA WGS on two cell types — single sperm (germline) and blood cells (somatic and constitutional reference) — from two donors, sequencing tens of cells per sample on PacBio HiFi at approximately 10× coverage per cell. We will (i) assess method performance, including coverage uniformity, allelic dropout, and sensitivity and false-discovery rates for SNVs, indels and SVs against the matched blood reference; and (ii) characterise somatic mosaicism and clonal structure within and between the sperm and blood compartments of each donor. The study will define the technical parameters and analysis workflow needed to scale single-cell long-read sequencing to larger germline and somatic-mosaicism cohorts.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008520","title":" Breast Cancer Atlas Research Consortium (BCARC)","description":"The Breast Cancer Atlas Research Consortium (BCARC) is an international translational research programme building a multi-modal atlas of breast cancer across subtypes, disease progression states, and treatment phases. Founding investigators span the Swarbrick Laboratory (Garvan Institute of Medical Research, Sydney), the Perou Laboratory (University of North Carolina at Chapel Hill), the Grimmond Laboratory (University of Melbourne Centre for Cancer Research), the Al'Khafaji Laboratory (Broad Institute of MIT and Harvard), and the Lundeberg Laboratory (KTH Royal Institute of Technology, Stockholm).\n\nSamples are drawn from primary and metastatic breast tumours together with matched adjacent tissues and where available, blood samples. All samples derive from participants consented under Garvan-approved research protocols. \n\nAccess is controlled and governed by the BCARC data access agreement; requests are reviewed by the Data Access Committee named in the associated policy record","abstract":"The Breast Cancer Atlas Research Consortium (BCARC) is an international translational research programme building a multi-modal atlas of breast cancer across subtypes, disease progression states, and treatment phases. Founding investigators span the Swarbrick Laboratory (Garvan Institute of Medical Research, Sydney), the Perou Laboratory (University of North Carolina at Chapel Hill), the Grimmond Laboratory (University of Melbourne Centre for Cancer Research), the Al'Khafaji Laboratory (Broad Institute of MIT and Harvard), and the Lundeberg Laboratory (KTH Royal Institute of Technology, Stockholm).\n\nSamples are drawn from primary and metastatic breast tumours together with matched adjacent tissues and where available, blood samples. All samples derive from participants consented under Garvan-approved research protocols. \n\nAccess is controlled and governed by the BCARC data access agreement; requests are reviewed by the Data Access Committee named in the associated policy record","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-08-06T09:11:20+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008521","title":"Targeted_NanoSeq___PSARC_and_ILD_","description":"This study aims to characterise the mutational landscape and identify driver mutations in auto-inflommatory lung disease and interstitial lung diseases (ILDs). Here, we will perform tissue ribboning and generate targeted NanoSeq data with fresh frozen bronchus and lung parenchymal tissues from patients with PSARC and ILDs in order to better understand the mutational processes in these diseases.      ","abstract":"This study aims to characterise the mutational landscape and identify driver mutations in auto-inflommatory lung disease and interstitial lung diseases (ILDs). Here, we will perform tissue ribboning and generate targeted NanoSeq data with fresh frozen bronchus and lung parenchymal tissues from patients with PSARC and ILDs in order to better understand the mutational processes in these diseases.      ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008522","title":"Whole-genome, methylome and transcriptome sequencing of human colorectal epithelial clones","description":"Epigenetic heterogeneity and its origin among somatic cells within the same cell-type remains poorly understood. By integrating whole-genome and whole-genome-methylome sequencing of 410 single-cell-derived colorectal epithelial clones from 15 donors, and transcriptome sequencing from most of the clones, we show that a somatic colorectal lineage accumulates ~1.2 million CpG epimutations by 60 years of age. Of these, ~0.75 million arise during early embryogenesis, which remain stable in somatic lineage for lifetime. The early embryonic epimutation rate exceeded 40,000 CpG changes per endogenous somatic mutation at the earliest molecular times, but declined to approximately ~150 changes per mutation by birth and remained at a similar level during postnatal ageing. These changes cluster at reproducible genomic hotspots, frequently overlap CpG islands and promoters, and are associated with persistent transcriptional differences. Early developmental epimutations also contribute to X-chromosome inactivation and escape in females, and loss-of-methylation at retrotransposition-competent LINE-1 source elements in adult colorectal epithelium. Finally, lineage-associated methylation patterns resolved phylogenetic branches not captured by somatic mutations alone. Our study establishes clonal multi-omics as a high-resolution framework for tracing the origin, persistence and functional consequences of somatic epigenetic mosaicism.\n","abstract":"Epigenetic heterogeneity and its origin among somatic cells within the same cell-type remains poorly understood. By integrating whole-genome and whole-genome-methylome sequencing of 410 single-cell-derived colorectal epithelial clones from 15 donors, and transcriptome sequencing from most of the clones, we show that a somatic colorectal lineage accumulates ~1.2 million CpG epimutations by 60 years of age. Of these, ~0.75 million arise during early embryogenesis, which remain stable in somatic lineage for lifetime. The early embryonic epimutation rate exceeded 40,000 CpG changes per endogenous somatic mutation at the earliest molecular times, but declined to approximately ~150 changes per mutation by birth and remained at a similar level during postnatal ageing. These changes cluster at reproducible genomic hotspots, frequently overlap CpG islands and promoters, and are associated with persistent transcriptional differences. Early developmental epimutations also contribute to X-chromosome inactivation and escape in females, and loss-of-methylation at retrotransposition-competent LINE-1 source elements in adult colorectal epithelium. Finally, lineage-associated methylation patterns resolved phylogenetic branches not captured by somatic mutations alone. Our study establishes clonal multi-omics as a high-resolution framework for tracing the origin, persistence and functional consequences of somatic epigenetic mosaicism.\n","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008523","title":"Raw sample data for ZERO Childhood Cancer Precision Medicine Program","description":"The Zero Childhood Cancer Program (ZERO) is Australia's first and most comprehensive precision medicine program for children and young people with cancer. Jointly led by the Children's Cancer Institute (CCI) and the Kids Cancer Centre at Sydney Children's Hospital, Randwick, it uses in-depth genomic analysis and laboratory testing to find personalised treatments for individual patients.","abstract":"The Zero Childhood Cancer Program (ZERO) is Australia's first and most comprehensive precision medicine program for children and young people with cancer. Jointly led by the Children's Cancer Institute (CCI) and the Kids Cancer Centre at Sydney Children's Hospital, Randwick, it uses in-depth genomic analysis and laboratory testing to find personalised treatments for individual patients.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-08-16T00:31:28+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008524","title":"Lung adenocarcinoma WHO histological classes contain distinct immune cell profiles","description":"Lung adenocarcinoma (LUAD) is classified internationally into six histological subtypes that predict clinical outcomes. Mutation analyses identify targets but provide less prognostic information than histological appearances. We therefore characterised relationships between WHO histological classification, common mutations, and underlying transcriptomic and immune profiles in 89 LUAD cases. Mutation profiles poorly correlated with histology or survival. Global gene expression was structured into 12 modules, identifying different tumour cells and pathways within WHO subtypes.","abstract":"To characterise relationships between WHO histological classification, common mutations, copy number aberrations and underlying transcriptomic and immune profiles in 89 lung adenocarcinoma (LUAD) cases have been studied.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008525","title":"Rapid, Comprehensive Methylation-Based Classification of Hematologic Malignancies by Nanopore Sequencing","description":null,"abstract":"Hematologic malignancies are diagnosed through a fragmented, sequential workup of morphology, immunophenotyping, cytogenetics, and molecular testing that can take days to weeks and is unavailable at many centers. DNA methylation profiling has transformed central nervous system tumor diagnosis, yet hematologic classifiers have remained confined to narrow acute leukemia panels. Here we present Lamprey, a deep-learning methylation classifier spanning 86 hematologic malignancy entities, trained on a reference cohort of 8,544 patients and deployed directly from nanopore sequencing. Lamprey is trained on simulated methylation profiles that reproduce the coverage sparsity and systematic caller bias of real nanopore data. Against blinded reference diagnoses across retrospective, external, and prospective cohorts, Lamprey exceeded 98% accuracy among classified cases. Lamprey reaches a confident call within minutes of a sequencing run, and cost as little as $82 per sample. Lamprey consolidates a sequential diagnostic workup into a single, rapid, same-day molecular readout.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008526","title":"CMML_TAP_Illumina__for_TAP_and_TAP_PCP_","description":"Whole genome methylation sequencing to determine HSC phylogeny in MDS and clonal haematopoiesis patients undergoing treatment with hypomethylating agents.","abstract":"Whole genome methylation sequencing to determine HSC phylogeny in MDS and clonal haematopoiesis patients undergoing treatment with hypomethylating agents.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008527","title":"CMML_5_base_Illumina__for_5B_and_5B_PCP_","description":"Whole genome methylation sequencing to determine HSC phylogeny in MDS and clonal haematopoiesis patients undergoing treatment with hypomethylating agents.","abstract":"Whole genome methylation sequencing to determine HSC phylogeny in MDS and clonal haematopoiesis patients undergoing treatment with hypomethylating agents.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008528","title":"CMML_WGS_Ultima_","description":"Whole genome methylation sequencing to determine HSC phylogeny in MDS and clonal haematopoiesis patients undergoing treatment with hypomethylating agents. ","abstract":"Whole genome methylation sequencing to determine HSC phylogeny in MDS and clonal haematopoiesis patients undergoing treatment with hypomethylating agents.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008529","title":"CMML_EMSeq_Ultima","description":"Whole genome methylation sequencing to determine HSC phylogeny in MDS and clonal haematopoiesis patients undergoing treatment with hypomethylating agents.","abstract":"Whole genome methylation sequencing to determine HSC phylogeny in MDS and clonal haematopoiesis patients undergoing treatment with hypomethylating agents.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008530","title":"CMML_TAP_Ultima","description":"Whole genome methylation sequencing to determine HSC phylogeny in MDS and clonal haematopoiesis patients undergoing treatment with hypomethylating agents.","abstract":"Whole genome methylation sequencing to determine HSC phylogeny in MDS and clonal haematopoiesis patients undergoing treatment with hypomethylating agents.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008531","title":"ScRNA-seq data of CPOs","description":"Raw matrices of scRNA-seq data of CTRL and LFS CPOs","abstract":"Raw matrices of scRNA-seq data of CTRL and LFS CPOs","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008532","title":"RNA-seq data of choroid plexus and telencephalic organoids","description":"RNA-seq data of choroid plexus and telencephalic organoids for LFS CPOs paper","abstract":"RNA-seq data of choroid plexus and telencephalic organoids for LFS CPOs paper","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008533","title":"RNA-seq data of Choroid Plexus Tumors","description":"RNA-seq data of CHoroid Plexus Tumors for LFS CPOs paper","abstract":"RNA-seq data of CHoroid Plexus Tumors for LFS CPOs paper","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008534","title":"Open_IBD_Virome","description":"Open-IBD, a longitudinal multi-omics inception cohort in IBD. Studying the biology of IBD from the point of diagnosis, without the confounders of time, uncontrolled inflammation and exposure to multiple therapies, provides an unparalleled opportunity for deriving biomarkers and mechanistic insights that aid the discovery and validation of therapeutic targets in IBD. 1000 confirmed newly diagnosed IBD patients will be sampled to collect intestinal biopsies at diagnosis and after one year from diagnosis. Blood and stool samples will be also collected at diagnosis and months 3, 6, 9, 12, 18 and 24 after. RNA and DNA will be extracted from buffered preserved stools samples to generate Virome shotgun sequencing data from 3800 samples covering IBD baseline (1000) and 12 month follow ups samples (1000) and targeted IBD samples due to clinical scenarios of interest (1400) : disease progression/ presurgery samples/ samples previous and post treatment to advanced therapies. Additionally, Virome data will also be generated from non IBD stool samples collected at diagnosis time (400). ","abstract":"Open-IBD, a longitudinal multi-omics inception cohort in IBD. Studying the biology of IBD from the point of diagnosis, without the confounders of time, uncontrolled inflammation and exposure to multiple therapies, provides an unparalleled opportunity for deriving biomarkers and mechanistic insights that aid the discovery and validation of therapeutic targets in IBD. 1000 confirmed newly diagnosed IBD patients will be sampled to collect intestinal biopsies at diagnosis and after one year from diagnosis. Blood and stool samples will be also collected at diagnosis and months 3, 6, 9, 12, 18 and 24 after. RNA and DNA will be extracted from buffered preserved stools samples to generate Virome shotgun sequencing data from 3800 samples covering IBD baseline (1000) and 12 month follow ups samples (1000) and targeted IBD samples due to clinical scenarios of interest (1400) : disease progression/ presurgery samples/ samples previous and post treatment to advanced therapies. Additionally, Virome data will also be generated from non IBD stool samples collected at diagnosis time (400). ","study_type":"Metagenomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008535","title":"Using a tumour-based classifier to identify genetic predisposition in Wilms tumour","description":null,"abstract":"Up to one-third of Wilms tumours (WTs) arise in the context of genetic or epigenetic predisposition, but identifying predisposed patients remains challenging because germline variants can be missed due to variable clinical presentation, mosaicism, and cryptic variants. We tested whether tumour-derived molecular patterns can reveal underlying predisposition independently of phenotype or germline findings.\nDNA methylation profiling of 138 WTs identified five molecular subgroups that captured biological and predisposition-associated heterogeneity, including enrichment for Beckwith-Wiedemann Spectrum tumours, and revealed a distinct WT1-driven subgroup. Cluster-guided reanalysis uncovered previously unrecognised WT1 pathogenic variants, including a newly identified germline variant that led to surveillance enrolment. A random forest classifier predicted WT1-driven tumours with ~90% accuracy across independent validation cohorts.\nTumour methylation profiling identifies biologically and clinically relevant WT subgroups and reliably detects a WT1-driven tumour methylation signature. This approach can guide targeted variant reanalysis, and uncover germline predisposition missed by standard diagnostic workflows.\n","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008536","title":"Comparative Genomic and Epigenomic Profiling of Brain Tumors Across Sequencing and Microarray Platforms","description":"This study systematically compared short-read 5-base sequencing, long-read Oxford Nanopore Technologies (ONT) sequencing, and Infinium EPICv2 microarrays for integrated genomic and epigenomic profiling of brain tumors. The cohort included 16 tumor samples initially diagnosed as glioblastoma, with 5-base and EPICv2 data available for all samples and ONT data for 10.","abstract":"This study systematically compared short-read 5-base sequencing, long-read Oxford Nanopore Technologies (ONT) sequencing, and Infinium EPICv2 microarrays for integrated genomic and epigenomic profiling of brain tumors. The cohort included 16 tumor samples initially diagnosed as glioblastoma, with 5-base and EPICv2 data available for all samples and ONT data for 10.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008537","title":"Spatial Omics Resolves Adrenergic and Mesenchymal Cell States in Neuroblastoma","description":"Neuroblastoma is a pediatric cancer arising from the developing sympathoadrenal lineage. Although cell lines derived from neuroblastoma patients have features of either adrenergic (ADRN) or mesenchymal (MES) cells, identifying MES cells in patient tumors is challenging and controversial. Here, to characterize intra- and inter-patient cellular heterogeneity, we analyze 54 neuroblastoma tumors spanning broad clinical, genetic, and histologic features using single-cell/single-nucleus RNA-sequencing (sc/snRNA-seq), bulk RNA-sequencing, spatial transcriptomics, and spatial proteomics. We show that tumor cells occupy distinct cellular neighborhoods separated from nonmalignant immune and stromal cells, yet established cell line-derived gene expression signatures fail to identify MES neuroblastoma cells. We therefore develop ADRN/MES signatures from early passage orthotopic patient-derived xenografts, enabling identification of MES tumor cells, validated by transcriptomic, epigenomic, proteomic, ultrastructural and functional assays. In patients, high MES gene expression correlates with worse event-free and overall survival. Together, this study provides a framework for defining clinically relevant neuroblastoma cell states.","abstract":"Neuroblastoma is a pediatric cancer arising from the developing sympathoadrenal lineage. Although cell lines derived from neuroblastoma patients have features of either adrenergic (ADRN) or mesenchymal (MES) cells, identifying MES cells in patient tumors is challenging and controversial. Here, to characterize intra- and inter-patient cellular heterogeneity, we analyze 54 neuroblastoma tumors spanning broad clinical, genetic, and histologic features using single-cell/single-nucleus RNA-sequencing (sc/snRNA-seq), bulk RNA-sequencing, spatial transcriptomics, and spatial proteomics. We show that tumor cells occupy distinct cellular neighborhoods separated from nonmalignant immune and stromal cells, yet established cell line-derived gene expression signatures fail to identify MES neuroblastoma cells. We therefore develop ADRN/MES signatures from early passage orthotopic patient-derived xenografts, enabling identification of MES tumor cells, validated by transcriptomic, epigenomic, proteomic, ultrastructural and functional assays. In patients, high MES gene expression correlates with worse event-free and overall survival. Together, this study provides a framework for defining clinically relevant neuroblastoma cell states.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-08-31T19:18:06+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008538","title":"OAC Operable Cohorts WGS","description":"Please see our related publication, 'Tumour DNA methylation subtypes and expression levels of CFISH (CXCL8, FCN1, IFI30, SLC11A1, HLA-DRA) predict response and overall survival to immunochemotherapy.'","abstract":"Please see our related publication, 'Tumour DNA methylation subtypes and expression levels of CFISH (CXCL8, FCN1, IFI30, SLC11A1, HLA-DRA) predict response and overall survival to immunochemotherapy.'","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008539","title":"OAC Operable Cohorts TAPS","description":"Please see our related publication, 'Tumour DNA methylation subtypes and expression levels of CFISH (CXCL8, FCN1, IFI30, SLC11A1, HLA-DRA) predict response and overall survival to immunochemotherapy.'","abstract":"Please see our related publication, 'Tumour DNA methylation subtypes and expression levels of CFISH (CXCL8, FCN1, IFI30, SLC11A1, HLA-DRA) predict response and overall survival to immunochemotherapy.'","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008540","title":"Multiome_profiling_of_bladder_cancer_organoids__snRNAseq_","description":"10X genomics Single-nucleus multiome profiling (ATAC-Seq+RNA-seq) of 6X bladder cancer organoid models to discover drivers of certain cell states. We will prepare these samples at CellGen and submit them for sequencing from there. ","abstract":"10X genomics Single-nucleus multiome profiling (ATAC-Seq+RNA-seq) of 6X bladder cancer organoid models to discover drivers of certain cell states. ","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008541","title":"Multiome_profiling_of_bladder_cancer_organoids__snATACseq_","description":"10X genomics Single-nucleus multiome profiling (ATAC-Seq+RNA-seq) of 6X bladder cancer organoid models to discover drivers of certain cell states. We will prepare these samples at CellGen and submit them for sequencing from there. ","abstract":"10X genomics Single-nucleus multiome profiling (ATAC-Seq+RNA-seq) of 6X bladder cancer organoid models to discover drivers of certain cell states.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008542","title":"SI cohort DNA methylation","description":null,"abstract":"Genome-wide DNA methylation profiles (Illumina Infinium MethylationEPIC array) from whole blood of 516 participants of the SI cohort.","study_type":"Epigenetics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008543","title":"Tumour DNA methylation subtypes and expression levels of CFISH (CXCL8, FCN1, IFI30, SLC11A1, HLA-DRA) predict response and overall survival to immunochemotherapy.","description":"Background:\n\nPredicting patient response to immunochemotherapy is vital but challenging and poorly studied in the (neo)adjuvant setting. We showed that tumour monocyte content (TMC) predicts overall survival of advanced oesophageal cancer (OC) in response to immunochemotherapy. We report clinical outcomes of 35 operable OC patients receiving ICI-based therapy, and molecular profiling of the unique phase-II LUD2015-005 trial treating 73 OC patients (38 advanced/inoperable and 35 operable) in the (neo)adjuvant setting.\n\nMethods:\n\nLUD2015-005 trial patients were treated with four-week immune checkpoint inhibitor (ICI)-only before combination with standard-of-care. Paired and longitudinally collected biopsies of tumour and multiple adjacent normal sites were bi-dissected to extract DNA and RNA. Whole-genome, DNA-methylome, single-cell and bulk RNA-sequencing data generated from the entire LUD2015-005 cohort were used for cell-deconvolution and data integration analysis.\n\nFindings:\n\nNeoadjuvant ICI-based combination therapy of operable OC in the LUD2015-005 trial revealed improved overall outcomes. Tumour monocytes contribute to tumour immune microenvironment (TiME) remodelling and associate with tumour reactive CD8+ T cells upon ICI+ chemotherapy/chemoradiotherapy. We identified five DNA-methylation subtypes with distinct TiME and a TMC-related five-gene signature CFISH (CXCL8, FCN1, IFI30, SLC11A1, HLA-DRA) as highly predictive biomarkers of overall survival in OC and beyond.\n\nConclusions:\n\nThese findings highlight the importance of the myeloid compartment in ICI response and the potential of CFISH and tumour DNA methylation in patient stratification for immunochemotherapy.\n\nFunding:\n\nThis work is mainly funded by Ludwig Institute for Cancer Research, CRUK Grants (A21998), (C30423/A2541), and NIHR Oxford Biomedical Research Centre. AstraZeneca UK Limited provided durvalumab and tremelimumab for LUD2015-005.","abstract":"Background:\n\nPredicting patient response to immunochemotherapy is vital but challenging and poorly studied in the (neo)adjuvant setting. We showed that tumour monocyte content (TMC) predicts overall survival of advanced oesophageal cancer (OC) in response to immunochemotherapy. We report clinical outcomes of 35 operable OC patients receiving ICI-based therapy, and molecular profiling of the unique phase-II LUD2015-005 trial treating 73 OC patients (38 advanced/inoperable and 35 operable) in the (neo)adjuvant setting.\n\nMethods:\n\nLUD2015-005 trial patients were treated with four-week immune checkpoint inhibitor (ICI)-only before combination with standard-of-care. Paired and longitudinally collected biopsies of tumour and multiple adjacent normal sites were bi-dissected to extract DNA and RNA. Whole-genome, DNA-methylome, single-cell and bulk RNA-sequencing data generated from the entire LUD2015-005 cohort were used for cell-deconvolution and data integration analysis.\n\nFindings:\n\nNeoadjuvant ICI-based combination therapy of operable OC in the LUD2015-005 trial revealed improved overall outcomes. Tumour monocytes contribute to tumour immune microenvironment (TiME) remodelling and associate with tumour reactive CD8+ T cells upon ICI+ chemotherapy/chemoradiotherapy. We identified five DNA-methylation subtypes with distinct TiME and a TMC-related five-gene signature CFISH (CXCL8, FCN1, IFI30, SLC11A1, HLA-DRA) as highly predictive biomarkers of overall survival in OC and beyond.\n\nConclusions:\n\nThese findings highlight the importance of the myeloid compartment in ICI response and the potential of CFISH and tumour DNA methylation in patient stratification for immunochemotherapy.\n\nFunding:\n\nThis work is mainly funded by Ludwig Institute for Cancer Research, CRUK Grants (A21998), (C30423/A2541), and NIHR Oxford Biomedical Research Centre. AstraZeneca UK Limited provided durvalumab and tremelimumab for LUD2015-005.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-09-07T10:43:53+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008544","title":"Comparative longitudinal scRNA-seq of PBMCs from IBD patients initiating biologic therapy alongside healthy age-matched controls","description":"In this study, we performed comparative longitudinal scRNA-seq of peripheral blood mononuclear cells (PBMCs) from 23 IBD patients initiating therapy with infliximab or ustekinumab, alongside healthy age-matched controls. Over 600,000 single-cell transcriptomes were profiled at baseline, two weeks, and six (anti-TNF) or eight (anti-[PR4.1]IL12/23) weeks post-treatment initiation, enabling high-resolution characterization of temporal immune-state transitions associated with both effective and ineffective therapeutic induction. We aimed to define candidate blood-based correlates of remission and non-remission and to benchmark shared versus therapy-context-specific immune programs We focused on myeloid, T -cell, and B -cell compartments and complemented the transcriptomic analyses with flow-cytometric, imaging-based, protein-level, and external dataset validation. This study provides a reference atlas of peripheral immune changes during anti-TNF and anti-IL-12/23 therapy and identifies candidate correlates for future biomarker development in IBD.","abstract":"In this study, we performed comparative longitudinal scRNA-seq of peripheral blood mononuclear cells (PBMCs) from 23 IBD patients initiating therapy with infliximab or ustekinumab, alongside healthy age-matched controls. Over 600,000 single-cell transcriptomes were profiled at baseline, two weeks, and six (anti-TNF) or eight (anti-[PR4.1]IL12/23) weeks post-treatment initiation, enabling high-resolution characterization of temporal immune-state transitions associated with both effective and ineffective therapeutic induction. We aimed to define candidate blood-based correlates of remission and non-remission and to benchmark shared versus therapy-context-specific immune programs We focused on myeloid, T -cell, and B -cell compartments and complemented the transcriptomic analyses with flow-cytometric, imaging-based, protein-level, and external dataset validation. This study provides a reference atlas of peripheral immune changes during anti-TNF and anti-IL-12/23 therapy and identifies candidate correlates for future biomarker development in IBD.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008545","title":"Homologous recombination deficiency detection in tumors of children with germline BRCA1, BRCA2 or PALB2 variants","description":null,"abstract":"We have collected whole genome sequencing data from 85 pediatric cancers of 80 patients with a heterozygous gPV in BRCA1, BRCA2 or PALB2, and assessed the presence of somatic second hits. The performance of markers for HR deficiency (HRD) was evaluated using seven cases of BRCA2-associated Fanconi anemia and an unselected cohort of 294 pediatric tumors. We have applied these markers to assess the HR status of tumors of pediatric BRCA1, BRCA2 or PALB2 gPV carriers.\nMarkers for HRD showed variable performance in pediatric cancer, with ID6 reaching the highest sensitivity and specificity. Although ID6 was detected in three tumors, only two osteosarcomas with a somatic second hit showed consistent evidence of HRD across multiple markers.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008546","title":"Targeted_NanoSeq___Somatic_mutations_in_oral_epithelium_of_Fanconi_Aneamia_patients","description":"Fanconi anaemia (FA) is a cancer-predisposition syndrome associated with a high risk of epithelial malignancies, providing an opportunity to study the earliest stages of carcinogenesis and their potential modification. In collaboration with the Rockefeller University, we are using buccal swabs as a non-invasive sampling strategy to characterise the somatic mutation and clonal landscape in oral epithelium from individuals with FA. By comparing patients exposed and unexposed to metformin, alongside previously characterised buccal epithelial cohorts (e.g. TwinsUK or BALANCE cohort), we aim to determine whether metabolic intervention is associated with changes in the burden and composition of mutant clones, including TP53-mutant populations. We might also receive blood samples as a comparator sample source, taking into account previous clinical history and metadata. ","abstract":"Fanconi anaemia (FA) is a cancer-predisposition syndrome associated with a high risk of epithelial malignancies, providing an opportunity to study the earliest stages of carcinogenesis and their potential modification. In collaboration with the Rockefeller University, we are using buccal swabs as a non-invasive sampling strategy to characterise the somatic mutation and clonal landscape in oral epithelium from individuals with FA. By comparing patients exposed and unexposed to metformin, alongside previously characterised buccal epithelial cohorts (e.g. TwinsUK or BALANCE cohort), we aim to determine whether metabolic intervention is associated with changes in the burden and composition of mutant clones, including TP53-mutant populations. We might also receive blood samples as a comparator sample source, taking into account previous clinical history and metadata.      ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008547","title":"Decellularized human bone scaffolds support hematopoietic stem and progenitor cell maintenance in a perfused 3D model of myelodysplastic neoplasms","description":"This study investigates hematopoietic and stromal cell states in a fully human perfusion-based three-dimensional bone marrow model using decellularized human trabecular bone. Single-cell RNA sequencing was performed on cultures generated with CD34+ cells from two patients with myelodysplastic neoplasms and two healthy donors. One MDS sample and one healthy donor sample were additionally profiled by Visium HD spatial transcriptomics to characterize spatial niche organization and disease-associated transcriptional states.","abstract":"This study investigates hematopoietic and stromal cell states in a fully human perfusion-based three-dimensional bone marrow model using decellularized human trabecular bone. Single-cell RNA sequencing was performed on cultures generated with CD34+ cells from two patients with myelodysplastic neoplasms and two healthy donors. One MDS sample and one healthy donor sample were additionally profiled by Visium HD spatial transcriptomics to characterize spatial niche organization and disease-associated transcriptional states.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008548","title":"CG_Brain_P_CBTN_Illumina_Spatial_Lee_Six_Managed","description":"This study aims to profile the spatial transcriptome of human skin and skin organoids using Illumina's new Spatial Technology. This assay uses a 1 um resolution lawn of barcoded oligos to capture mRNA from fresh frozen tissue sections. 3' RT is used to generate a cDNA library representative of the tissue transcriptome at 1 um resolution, which is subjected to short-read sequencing and reconciled with an image of the tissue sections to produce a spatial map of gene expression.","abstract":"This study aims to profile the spatial transcriptome of human skin and skin organoids using Illumina's new Spatial Technology. This assay uses a 1 um resolution lawn of barcoded oligos to capture mRNA from fresh frozen tissue sections. 3' RT is used to generate a cDNA library representative of the tissue transcriptome at 1 um resolution, which is subjected to short-read sequencing and reconciled with an image of the tissue sections to produce a spatial map of gene expression.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008549","title":"Neuroblastoma Single-Cell T Cell Receptor Atlas maps Subset-Specific Clonal Expansion and Inhibitory Receptors","description":null,"abstract":"T cell immunotherapies have shown first promise for pediatric high-risk neuroblastoma (HR-NB) patients, but their efficacy remains suboptimal. To enhance it, a better understanding of T cell states and inhibitory interactions in these MHC-Ilow tumors is required. We generated a comprehensive single-cell RNA,  and  T cell receptor (TCR) sequencing atlas encompassing &gt; 200.000 cells, of matched tumor and blood samples of 10 HR-NB patients, pre- and post-chemotherapy. CD8+ effector memory T cells were clonally expanded in patient blood and tumor, with signatures of T cell activation, but little evidence of tumor reactivity and low cytotoxic capacity in the tumor. Tumor-specific clonal expansion and gene signatures of tumor reactivity were observed in two CD4+ memory subsets with a Th17 and Tfh profile, respectively. In addition, tumors were enriched for V1+ T cells, particularly post-chemotherapy, which demonstrated clonal expansion in some patients and gene signatures of TCR engagement. These findings suggest that CD4+ and V1+ T cell subsets may act as key players in neuroblastoma immunity, while CD8+ T cells are hampered by low tumoral MHC-I expression. Importantly, we identified subset-specific and expansion-specific inhibitory receptors - CTLA4 (CD4+), TNFSF9 (CD8+) and FCRL6 and KIRs (V1+) which may serve as targets for immunotherapy. Overall, this single-cell atlas provides a comprehensive resource for deep characterization of T cell responses against neuroblastoma and a model for T cell reactivity. The identification of subset-specific inhibitory receptors may inform future strategies for more targeted immunotherapies.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008550","title":"Genome-wide SNP genotype and phenotype data from the Expanded National Nutrition Survey (ENNS), Philippines","description":"This study contains genome-wide SNP genotype data and associated phenotype data generated from participants of the Expanded National Nutrition Survey (ENNS) conducted by the Department of Science and Technology–Food and Nutrition Research Institute (DOST-FNRI), Philippines. Genotyping was performed using the Illumina Global Screening Array (GSA) v3.0 and the Thermo Fisher Axiom PanGenomiX Array. The associated phenotype dataset includes anthropometric, demographic, socioeconomic, and nutrition-related variables collected through standardized survey procedures. The dataset has been deposited to support reproducibility and secondary analyses of research on genetic determinants of nutritional status and related health outcomes. Access to individual-level data is controlled by the DOST-FNRI Data Access Committee and is granted only to qualified researchers whose proposed use is consistent with participant consent, ethical approvals, and applicable data protection requirements.","abstract":"This study contains genome-wide SNP genotype data and associated phenotype data generated from participants of the Expanded National Nutrition Survey (ENNS) conducted by the Department of Science and Technology–Food and Nutrition Research Institute (DOST-FNRI), Philippines. Genotyping was performed using the Illumina Global Screening Array (GSA) v3.0 and the Thermo Fisher Axiom PanGenomiX Array. The associated phenotype dataset includes anthropometric, demographic, socioeconomic, and nutrition-related variables collected through standardized survey procedures. The dataset has been deposited to support reproducibility and secondary analyses of research on genetic determinants of nutritional status and related health outcomes. Access to individual-level data is controlled by the DOST-FNRI Data Access Committee and is granted only to qualified researchers whose proposed use is consistent with participant consent, ethical approvals, and applicable data protection requirements.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008551","title":"CG_Multi_Multi_UCC_Behjati_WGS","description":"WGS of a family cohort suspected to contain an unusual multi-generational copy number change.","abstract":"WGS of a family cohort suspected to contain an unusual multi-generational copy number change.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008552","title":"Exome_Nanoseq__SDS_","description":"The mutational landscape of SDS will be characterized using whole exome nanoseq. Samples have been sourced from the Cambridge Blood and Stemcell Biobank (CBSB).","abstract":"The mutational landscape of SDS will be characterized using whole exome nanoseq. Samples have been sourced from the Cambridge Blood and Stemcell Biobank (CBSB).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008553","title":"Longitudinal analysis investigates expression signatures of anti-TNF therapy response in biopsies in inflammatory bowel disease","description":"We explored dynamics of therapy response in a cohort of IBD patients receiving first time infliximab therapy (18 patients) or first time vedolizumab therapy (14 patients). Biopsy samples were collected at up to 7 timepoints (from baseline to 14 weeks after therapy induction).","abstract":"We explored dynamics of therapy response in a cohort of IBD patients receiving first time infliximab therapy (18 patients) or first time vedolizumab therapy (14 patients). Biopsy samples were collected at up to 7 timepoints (from baseline to 14 weeks after therapy induction).","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008554","title":"Immunogenetics_landscape_of_individuals_with_rare_cancers_","description":"Identify somatic mutations in immune cell subsets from TP53 and PTEN carriers of pathogenic germline mutations and highly predisposed to develop cancer.","abstract":"Li-Fraumeni Syndrome (LFS) and PTEN Hamartomous Tumor Syndrome (PHTS) are rare cancers predisposition syndromes caused by pathogenic germline variations in the two well-known tumor suppressor genes, TP53 and PTEN, respectively. Both syndromes are associated with a high, lifelong risk of a broad spectrum of cancers in LFS and PHTS individuals. The impact of mutated P53 and PTEN in immune surveillance and tumour progression has been observed in human and mouse models. While recent studies have highlighted a well-established link between immune dysregulation and an elevated risk of cancer, primarily due to the failure of immune surveillance, very few studies have shed light on our understanding of the impact of the loss-of-function in PTEN and p53, the impairment of the immune response in LFS and PHTS individuals, and their role in the development of malignancy. We have previously optimised a multicolour panel to phenotype and sort immune cell populations by using spectrum flow cytometry in those individuals.  This proposal aims to draw the immune landscape from the blood compartment and identify the molecular signatures of six key immune cell populations (CD4+ T naïve, CD4+ T memory, CD8+ T naïve, CD8+ T memory, Tregs and B cells). We will collect blood samples of LFS, PHTS and healthy individuals, ten from each group. Phenotyping immune cells with our panel and identification of immune dysregulation signatures of sorted cells through full transcriptomic. Quantification of somatic mutational burden and signatures will be performed using a high sensitivity and low error rate duplex sequencing method (NanoSeq). Plasma cytokine levels and secreted forms of p53 and PTEN will be quantified through Olink, a high-throughput and sensitive technique. Tackling the cellular and molecular functions of these important genes and their regulation of the immune system in highly predisposed individuals with cancer recurrence, will bring improved understanding of the relationship of the immune response and cancer development. These insights will provide invaluable information that could guide the risk stratification strategies, early intervention, provide putative immunomarkers of cancer susceptibility and identify putative targets for novel immunotherapeutic development.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008555","title":"SGP_Martincorena_thyroid_Illumina__spatial_pilot_managed","description":"This study aims to profile the spatial transcriptome of human thyroid tissue using Illumina's new spatial transcriptomics StrataMap technology. This assay uses a 1 um resolution lawn of barcoded oligos to capture mRNA from fresh frozen tissue sections. 3' RT is used to generate a cDNA library representative of the tissue transcriptome at 1 um resolution, which is subjected to short-read sequencing and reconciled with an image of the tissue sections to produce a spatial map of gene expression.","abstract":"This study aims to profile the spatial transcriptome of human thyroid tissue using Illumina's new spatial transcriptomics StrataMap technology. This assay uses a 1 um resolution lawn of barcoded oligos to capture mRNA from fresh frozen tissue sections. 3' RT is used to generate a cDNA library representative of the tissue transcriptome at 1 um resolution, which is subjected to short-read sequencing and reconciled with an image of the tissue sections to produce a spatial map of gene expression.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008556","title":"RNA, CITE, and Methylation profiling in AML","description":"To characterize multiomic variance in acute myeloid leukemia, we generated DNA methylation data (Illumina MethylationEPIC; n=111 patients) and single-cell transcriptomic and surface-protein data (n=6 patients). The methylation data were integrated with existing bulk transcriptomic and targeted gene-panel sequencing data, mass-spectrometry-based proteomics and ex vivo drug profiling data. The CITE-seq data, from another cohort of patients, were used to examine  the resulting multiomic programs at single-cell resolution","abstract":"To characterize multiomic variance in acute myeloid leukemia, we generated DNA methylation data (Illumina MethylationEPIC; n=111 patients) and single-cell transcriptomic and surface-protein data (n=6 patients). The methylation data were integrated with existing bulk transcriptomic and targeted gene-panel sequencing data, mass-spectrometry-based proteomics and ex vivo drug profiling data. The CITE-seq data, from another cohort of patients, were used to examine  the resulting multiomic programs at single-cell resolution","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008557","title":"Structural variation in repeat elements is widespread in normal human tissues and in tumorigenesis","description":null,"abstract":"Somatic mosaicism is a fundamental source of genomic variation, yet the existence and developmental timing of large postzygotic structural variants remain largely unknown. We performed whole-genome long-read and short-read sequencing of DNA of multiple tissues from eight individuals (n=47 tissues; n=168 samples) to identify genome-wide mosaic structural variants. We found mosaic structural variation in every individual, impacting a median 285.2 kilobases per genome, and arising across tissues from all germ layers, consistent with both early and late developmental origins. Over 85% of mosaic structural variants were repeat-element mediated, with early embryonic variants clustering in early-replicating gene-rich regions, and post-gastrulation variants favoring late-replicating regions. Despite their large size and complexity, nearly half of evaluable structural variants were independently validated using a newly developed approach for identifying novel sequence breakpoints. Mosaic breakpoints were enriched within exons compared to germline variants, with 8.3% overlapping exons or cis-regulatory elements, suggesting that a substantial fraction of such changes may impact genome function. To extend these analyses in samples where long-read sequencing may not be possible, we measured genome-wide changes in repeat landscapes from short-read sequencing, recapitulating tissue-specific differences in mosaicism of structural variants. Using this approach, we characterized tumor- and tissue-specific variation in repeat elements across 15 cancer types, identifying changes across normal tissues, pre-cancer lesions, as well as early and advanced cancers. We found tumor-related repeat element variation to be similar in scale to that of mosaic variation across normal tissues. Tracking repeat landscape alterations in cell-free DNA provided a noninvasive approach for measuring tumor response during therapy. Our analyses revealed repeat-driven structural variation as a widespread phenomenon in health and disease.","study_type":"Cancer Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008558","title":"A cellular and vascular atlas of the breast tumor microenvironment with multi-resolution spatial transcriptomics","description":"Spatial transcriptomic profiling of human breast tumors to define high endothelial venule (HEV) states associated with tertiary lymphoid structures (TLSs). Includes 10x Genomics Visium data from 40 sections (33 tumor sections from 32 tumors, one profiled in duplicate, plus 7 matched uninvolved lymph nodes) and Visium HD data from 4 tumors. We identify a stromal \"primed\" HEV state carrying STING-associated and adhesive programs, and a mature TLS-associated state additionally marked by lymphotoxin-β receptor signaling, perivascular CCL19/CCL21 expression, and SPP1. Together these define a candidate endothelial maturation axis linked to TLS organization.","abstract":"Spatial transcriptomic profiling of human breast tumors to define high endothelial venule (HEV) states associated with tertiary lymphoid structures (TLSs). Includes 10x Genomics Visium data from 40 sections (33 tumor sections from 32 tumors, one profiled in duplicate, plus 7 matched uninvolved lymph nodes) and Visium HD data from 4 tumors. We identify a stromal \"primed\" HEV state carrying STING-associated and adhesive programs, and a mature TLS-associated state additionally marked by lymphotoxin-β receptor signaling, perivascular CCL19/CCL21 expression, and SPP1. Together these define a candidate endothelial maturation axis linked to TLS organization.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":true,"released_date":"2026-09-21T23:38:11+02:00","is_deprecated":false},
{"accession_id":"EGAS00001008559","title":"SNP array and WES profiling of bladder cancerized field","description":"Histologically normal tissues adjacent to tumors, the so-called cancerized field, contain molecular alterations that can provide insight into tumor development and its environment. However, the somatic copy number and single nucleotide variant landscape of the bladder cancerized field remains poorly characterized. Here we profiled 746 tumors, histologically normal adjacent tissue (NAT) and blood samples collected from 104 patients with bladder cancer by SNP array, and performed whole-exome sequencing analysis on 140 samples from 38 patients. We identified recurrent copy number alterations and oncogenic variants shared between tumors and matched NATs, consistent with their occurrence prior to tumor formation. These alterations affected two cancer-relevant pathways through distinct genetic mechanisms: FGFR signaling, via amplification of FRS2 within a recurrent 12q15 amplicon and FGFR3 variants, and chromatin remodeling, via co-amplification of YEATS4 within the same amplicon and (likely) oncogenic variants in KMT2D and KDM6A. The TERT promoter c.−124C&gt;T variant was the most prevalent shared event, detected in both NAT and tumor in 45% of patients. APOBEC-associated mutational signatures were detected in NATs and were significantly enriched in tumors, where they were restricted to clonal lineages shared with or specific to the tumor. Moreover, analysis of non-tumor samples revealed genomic alteration patterns that were not apparent from tumor samples alone, such as distinct chromosomal instability patterns associated with tumor advancement and smoking history, as well as higher copy number burden in males and in patients without a family history of cancer. Together, these findings demonstrate that histologically normal adjacent tissues harbor genomic alterations shared with bladder tumors and reveal features of cancer development that are not captured by tumor analysis alone.","abstract":"Histologically normal tissues adjacent to tumors, the so-called cancerized field, contain molecular alterations that can provide insight into tumor development and its environment. However, the somatic copy number and single nucleotide variant landscape of the bladder cancerized field remains poorly characterized. Here we profiled 746 tumors, histologically normal adjacent tissue (NAT) and blood samples collected from 104 patients with bladder cancer by SNP array, and performed whole-exome sequencing analysis on 140 samples from 38 patients. We identified recurrent copy number alterations and oncogenic variants shared between tumors and matched NATs, consistent with their occurrence prior to tumor formation. These alterations affected two cancer-relevant pathways through distinct genetic mechanisms: FGFR signaling, via amplification of FRS2 within a recurrent 12q15 amplicon and FGFR3 variants, and chromatin remodeling, via co-amplification of YEATS4 within the same amplicon and (likely) oncogenic variants in KMT2D and KDM6A. The TERT promoter c.−124C&gt;T variant was the most prevalent shared event, detected in both NAT and tumor in 45% of patients. APOBEC-associated mutational signatures were detected in NATs and were significantly enriched in tumors, where they were restricted to clonal lineages shared with or specific to the tumor. Moreover, analysis of non-tumor samples revealed genomic alteration patterns that were not apparent from tumor samples alone, such as distinct chromosomal instability patterns associated with tumor advancement and smoking history, as well as higher copy number burden in males and in patients without a family history of cancer. Together, these findings demonstrate that histologically normal adjacent tissues harbor genomic alterations shared with bladder tumors and reveal features of cancer development that are not captured by tumor analysis alone.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008560","title":"Cross-cohort reproducibility supports implementation of nanopore methylation sequencing for AI-assisted diagnosis of adult CNS tumors","description":"Accurate classification of central nervous system (CNS) tumors is essential for patient treatment and prognosis. Genome-wide DNA methylation profiling is now integral to WHO 2021 CNS5 classification. Although array-based methylation profiling with the Heidelberg classifier is widely used, a fast, more streamlined workflow is needed for broad implementation. We therefore evaluated the diagnostic equivalence of a nanopore workflow combining the deep learning-based Sturgeon v2 classifier with genome-wide copy number aberration (CNA) analysis against a WHO 2021 CNS5-compliant integrated reference diagnosis.","abstract":"Accurate classification of central nervous system (CNS) tumors is essential for patient treatment and prognosis. Genome-wide DNA methylation profiling is now integral to WHO 2021 CNS5 classification. Although array-based methylation profiling with the Heidelberg classifier is widely used, a fast, more streamlined workflow is needed for broad implementation. We therefore evaluated the diagnostic equivalence of a nanopore workflow combining the deep learning-based Sturgeon v2 classifier with genome-wide copy number aberration (CNA) analysis against a WHO 2021 CNS5-compliant integrated reference diagnosis.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008561","title":"Integrative epigenomic and transcriptomic analyses reveal regulatory epigenetic reprogramming in Kearns-Sayre syndrome","description":"Kearns-Sayre syndrome (KSS) is a rare mitochondrial disorder associated with single large-scale mitochondrial DNA deletions. This multicenter cross-sectional study investigates epigenomic and transcriptomic alterations in primary skin fibroblasts from 12 patients with KSS and 11 age- and sex-matched healthy controls. Genome-wide DNA methylation was profiled using the Illumina Infinium MethylationEPIC v2.0 BeadChip, and transcriptomic profiling was performed by paired-end RNA sequencing using the Illumina NovaSeq 6000 platform. Integrative analyses of DNA methylation and gene expression were performed to identify epigenetically regulated genes and molecular pathways potentially involved in KSS pathophysiology.","abstract":"Kearns-Sayre syndrome (KSS) is a rare mitochondrial disorder associated with single large-scale mitochondrial DNA deletions. This multicenter cross-sectional study investigates epigenomic and transcriptomic alterations in primary skin fibroblasts from 12 patients with KSS and 11 age- and sex-matched healthy controls. Genome-wide DNA methylation was profiled using the Illumina Infinium MethylationEPIC v2.0 BeadChip, and transcriptomic profiling was performed by paired-end RNA sequencing using the Illumina NovaSeq 6000 platform. Integrative analyses of DNA methylation and gene expression were performed to identify epigenetically regulated genes and molecular pathways potentially involved in KSS pathophysiology.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008562","title":"A South African genome-wide association study and multi-ancestry meta-analysis identifies novel loci associated with cervical cancer","description":"Cervical cancer is common in sub-Saharan Africa, with high mortality rates. However, most genome-wide association studies (GWAS) of cervical cancer have been performed in women of European and Asian ancestry. To identify additional novel loci associated with cervical cancer, we performed the first GWAS of cervical cancer in black South African women (n=2,912), followed by a multi-ancestry meta-analysis (n=515,135). We also performed fine mapping, functional annotation of associated loci, and assessed the performance of polygenic risk scores (PRS) derived from GWAS summary data from women of African, European, and East Asian ancestry. We identified four genome-wide significant novel loci, rs113842373 (GALNT13/RPRM),  rs6800994 (ZMAT3/PIK3CA), rs75372437 (ZMAT4), and rs2515273 (ANO1), associated with cervical cancer in black South African women. We further identified two novel loci, rs2213307 (HLA-DPA1:HLA-DPB1), and rs3132954 (TSBP1/BTNL2) associated with cervical cancer in a multi-ancestry meta-analysis.  Bayesian fine-mapping identified five loci (rs113842373, rs9810920, rs466502, rs2523496, and rs75372437) with posterior probabilities (PP) of causality &gt;0.99, driving the association. PRSs derived from multi-ancestry GWAS summary data provided improved prediction   (R2 =1.92%, p=1.07x 10-07) compared to those derived from ancestry-specific GWAS summary data. In conclusion, we identified novel loci associated with cervical cancer in women of diverse ancestry, with fine mapping revealing high PP causality loci. Multi-ancestry PRSs outperformed ancestry-specific PRSs for cervical cancer. Our findings highlight the importance and power of diversity in genetic studies in uncovering population-specific and shared genetic loci that contribute to cervical cancer susceptibility. ","abstract":"Cervical cancer is common in sub-Saharan Africa, with high mortality rates. However, most genome-wide association studies (GWAS) of cervical cancer have been performed in women of European and Asian ancestry. To identify additional novel loci associated with cervical cancer, we performed the first GWAS of cervical cancer in black South African women (n=2,912), followed by a multi-ancestry meta-analysis (n=515,135). We also performed fine mapping, functional annotation of associated loci, and assessed the performance of polygenic risk scores (PRS) derived from GWAS summary data from women of African, European, and East Asian ancestry. We identified four genome-wide significant novel loci, rs113842373 (GALNT13/RPRM),  rs6800994 (ZMAT3/PIK3CA), rs75372437 (ZMAT4), and rs2515273 (ANO1), associated with cervical cancer in black South African women. We further identified two novel loci, rs2213307 (HLA-DPA1:HLA-DPB1), and rs3132954 (TSBP1/BTNL2) associated with cervical cancer in a multi-ancestry meta-analysis.  Bayesian fine-mapping identified five loci (rs113842373, rs9810920, rs466502, rs2523496, and rs75372437) with posterior probabilities (PP) of causality &gt;0.99, driving the association. PRSs derived from multi-ancestry GWAS summary data provided improved prediction   (R2 =1.92%, p=1.07x 10-07) compared to those derived from ancestry-specific GWAS summary data. In conclusion, we identified novel loci associated with cervical cancer in women of diverse ancestry, with fine mapping revealing high PP causality loci. Multi-ancestry PRSs outperformed ancestry-specific PRSs for cervical cancer. Our findings highlight the importance and power of diversity in genetic studies in uncovering population-specific and shared genetic loci that contribute to cervical cancer susceptibility. ","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008563","title":"Biological sex structures immune remodeling associated with latent human cytomegalovirus infection","description":null,"abstract":"This study investigates sex-dependent systemic immune remodeling associated with latent human cytomegalovirus infection. This submission contains controlled-access raw paired-end H3K27ac ChIP-seq FASTQ files from human peripheral blood mononuclear cells used for descriptive chromatin profiling, together with the corresponding input control library.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008564","title":"CG_Pancreas_A_nPOD_Biobank_T2D_RNA_Lotfollahi_Managed","description":"Characterisation of the Human Pancreas in Type 2 Diabetes at Single Cell Resolution","abstract":"This project uses high-resolution single cell and spatial transcriptomics to characterise the cellular composition and organisation of the human pancreas in the context of type 2 diabetes (T2D). The aim is to map endocrine, exocrine, stromal, and immune cell populations within intact tissue and define their spatial relationships. We focus on identifying cell-type-specific transcriptional programs and potential cell–cell communication interactions within the pancreatic microenvironment. The data will be used to generate a spatially resolved atlas of pancreatic tissue and to support integrative analyses with complementary single-cell datasets. Overall, this work aims to provide a detailed framework for studying tissue architecture and cellular interactions relevant to T2D.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008565","title":"Congo genetic diversity","description":"This study characterises genetic diversity in hunter-gatherer and neighbouring farming communities in the northern Republic of the Congo. The dataset comprises genotype data from 287 individuals generated using the H3Africa genotyping array, providing a resource for investigating patterns of genetic diversity and population structure in Central African populations.","abstract":"This study characterises genetic diversity in hunter-gatherer and neighbouring farming communities in the northern Republic of the Congo. The dataset comprises genotype data from 287 individuals generated using the H3Africa genotyping array, providing a resource for investigating patterns of genetic diversity and population structure in Central African populations.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008566","title":"CG_Multi_P_23P108_Behjati_ScRNA_Managed","description":"We have a case of two siblings (twins) who were born with nodular blue rashes over their body. The first twin had a large periorbital subcutaneous mass which was diagnosed as infantile undifferentiated sarcoma. This baby was too systematically unwell for chemotherapy and died at 12 days of age. The second sibling received two cycles of emergency chemotherapy however died due to disease progression and secondary haemorrhage at 2 months of age. Post-mortem normal and tumour samples have been taken. In addition to placental tissue and parental germline DNA, the goal will be to investigate intra-uterine transfer of sarcoma and the phylogenetic relationship of tumours in both twins.","abstract":"We have a case of two siblings (twins) who were born with nodular blue rashes over their body. The first twin had a large periorbital subcutaneous mass which was diagnosed as infantile undifferentiated sarcoma. This baby was too systematically unwell for chemotherapy and died at 12 days of age. The second sibling received two cycles of emergency chemotherapy however died due to disease progression and secondary haemorrhage at 2 months of age. Post-mortem normal and tumour samples have been taken. In addition to placental tissue and parental germline DNA, the goal will be to investigate intra-uterine transfer of sarcoma and the phylogenetic relationship of tumours in both twins.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008567","title":"CG_Multi_P_G17228_Behjati_ScRNA_Managed","description":"This child was diagnosed and succumbed to a stage 4S Neuroblastoma, these usually have an extremely good prognosis however in this case, uniquely presented with aggressive disease. This presents us with the opportunity to establish if the stage 4S disease was metastatic or had synchronous primary tumours, as well as analysis regarding the genetic relationship between normal and tumour.","abstract":"This child was diagnosed and succumbed to a stage 4S Neuroblastoma, these usually have an extremely good prognosis however in this case, uniquely presented with aggressive disease. This presents us with the opportunity to establish if the stage 4S disease was metastatic or had synchronous primary tumours, as well as analysis regarding the genetic relationship between normal and tumour.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008568","title":"CG_Gastric_A_UCAM_Illumina_RNA_Lotfollahi_Managed","description":"This study aims to profile the spatial transcriptome of gastric tumours using Illumina's new Spatial Technology. This assay uses a 1 um resolution lawn of barcoded oligos to capture mRNA from fresh frozen tissue sections. 3' RT is used to generate a cDNA library representative of the tissue transcriptome at 1 um resolution, which is subjected to short-read sequencing and reconciled with an image of the tissue sections to produce a spatial map of gene expression.","abstract":"This study aims to profile the spatial transcriptome of gastric tumours using Illumina's new Spatial Technology. This assay uses a 1 um resolution lawn of barcoded oligos to capture mRNA from fresh frozen tissue sections. 3' RT is used to generate a cDNA library representative of the tissue transcriptome at 1 um resolution, which is subjected to short-read sequencing and reconciled with an image of the tissue sections to produce a spatial map of gene expression.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008569","title":"CG_Brain_Cell_Line_LEAP_Delta_Illumina_Spatial_Bayraktar_Open","description":"This study aims to profile the spatial transcriptome of human skin and skin organoids using Illumina's new Spatial Technology. This assay uses a 1 um resolution lawn of barcoded oligos to capture mRNA from fresh frozen tissue sections. 3' RT is used to generate a cDNA library representative of the tissue transcriptome at 1 um resolution, which is subjected to short-read sequencing and reconciled with an image of the tissue sections to produce a spatial map of gene expression.","abstract":"This study aims to profile the spatial transcriptome of human skin and skin organoids using Illumina's new Spatial Technology. This assay uses a 1 um resolution lawn of barcoded oligos to capture mRNA from fresh frozen tissue sections. 3' RT is used to generate a cDNA library representative of the tissue transcriptome at 1 um resolution, which is subjected to short-read sequencing and reconciled with an image of the tissue sections to produce a spatial map of gene expression.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008570","title":"CG_Pancreas_A_UCAM_Xenium_Lotfollahi_Managed","description":"Molecular biomarkers in pancreatic cyst fluid to improve diagnostic accuracy and malignancy risk assessment (PACE Study)","abstract":"Looking at the changes in the tumour microenvironment in patients with pancreatic, bile duct, or gallbladder cancer. The tumour microenvironment is the area of tissue around the tumour, and previous studies have shown that this plays an important role in controlling the aggressiveness of the tumour and also response to treatment.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008571","title":"This is a test on how XMLs look ","description":"Testing if abstract gets updated","abstract":"Testing if abstract gets updated","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008572","title":"1342_HUM_ML_DARA_PAMGEN","description":"Spot Malaria aims to bring together malaria genetics with epidemiological information across both time and space. The project has two distinct but complementary goals; to simplify genetic data reporting so that more users are able to analyse and interpret the key features of their data, focusing on what is of most importance for field research and malaria control in a timely manner; and to create an open access global observatory across time and space for genetic variation and other relevant metadata such as malaria prevalence and deployment of control measures. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Spot Malaria aims to bring together malaria genetics with epidemiological information across both time and space. The project has two distinct but complementary goals; to simplify genetic data reporting so that more users are able to analyse and interpret the key features of their data, focusing on what is of most importance for field research and malaria control in a timely manner; and to create an open access global observatory across time and space for genetic variation and other relevant metadata such as malaria prevalence and deployment of control measures.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008573","title":"1343_HUM_ET_GOLASSA_PAMGEN","description":"Spot Malaria aims to bring together malaria genetics with epidemiological information across both time and space. The project has two distinct but complementary goals; to simplify genetic data reporting so that more users are able to analyse and interpret the key features of their data, focusing on what is of most importance for field research and malaria control in a timely manner; and to create an open access global observatory across time and space for genetic variation and other relevant metadata such as malaria prevalence and deployment of control measures. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Spot Malaria aims to bring together malaria genetics with epidemiological information across both time and space. The project has two distinct but complementary goals; to simplify genetic data reporting so that more users are able to analyse and interpret the key features of their data, focusing on what is of most importance for field research and malaria control in a timely manner; and to create an open access global observatory across time and space for genetic variation and other relevant metadata such as malaria prevalence and deployment of control measures.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008574","title":"1344_HUM_CM_APINJOH_PAMGEN","description":"Spot Malaria aims to bring together malaria genetics with epidemiological information across both time and space. The project has two distinct but complementary goals; to simplify genetic data reporting so that more users are able to analyse and interpret the key features of their data, focusing on what is of most importance for field research and malaria control in a timely manner; and to create an open access global observatory across time and space for genetic variation and other relevant metadata such as malaria prevalence and deployment of control measures. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Spot Malaria aims to bring together malaria genetics with epidemiological information across both time and space. The project has two distinct but complementary goals; to simplify genetic data reporting so that more users are able to analyse and interpret the key features of their data, focusing on what is of most importance for field research and malaria control in a timely manner; and to create an open access global observatory across time and space for genetic variation and other relevant metadata such as malaria prevalence and deployment of control measures.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008575","title":"1345_HUM_MG_RANDRIANARIVELOJOSIA_PAMGEN","description":"Spot Malaria aims to bring together malaria genetics with epidemiological information across both time and space. The project has two distinct but complementary goals; to simplify genetic data reporting so that more users are able to analyse and interpret the key features of their data, focusing on what is of most importance for field research and malaria control in a timely manner; and to create an open access global observatory across time and space for genetic variation and other relevant metadata such as malaria prevalence and deployment of control measures. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/","abstract":"Spot Malaria aims to bring together malaria genetics with epidemiological information across both time and space. The project has two distinct but complementary goals; to simplify genetic data reporting so that more users are able to analyse and interpret the key features of their data, focusing on what is of most importance for field research and malaria control in a timely manner; and to create an open access global observatory across time and space for genetic variation and other relevant metadata such as malaria prevalence and deployment of control measures.","study_type":"Whole Genome Sequencing","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008576","title":"Human_Genetic_Interactions_","description":"Dual gene knockout using CRISPR to study human genetic interactions.","abstract":"R&amp;D project to see genetic interaction across human genome.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008577","title":"EuCARE (European Cohorts of Patients and Schools to Advance Response to Epidemics) is a Horizon Europe project addressing the COVID-19 pandemic and emerging SARS-CoV-2 variants. This submission contains pseudonymized clinical and laboratory data from","description":"EuCARE (European Cohorts of Patients and Schools to Advance Response to Epidemics) is a Horizon Europe project addressing the COVID-19 pandemic and emerging SARS-CoV-2 variants. This submission contains pseudonymized clinical and laboratory data from the EuCARE clinical cohort studies, which have enrolled over 50,000 patients across three cohorts: Hospitalised COVID-19 patients, Post-COVID long-term sequelae, and Health Care Workers (HCW). The studies evaluate the association between circulating SARS-CoV-2 variants and short, mid and long-term clinical outcomes. Data submitted here includes participant-level clinical variables collected as part of the EuCARE clinical cohort studies.","abstract":"EuCARE (European Cohorts of Patients and Schools to Advance Response to Epidemics) is a Horizon Europe project addressing the COVID-19 pandemic and emerging SARS-CoV-2 variants. This submission contains pseudonymized clinical and laboratory data from the EuCARE clinical cohort studies, which have enrolled over 50,000 patients across three cohorts: Hospitalised COVID-19 patients, Post-COVID long-term sequelae, and Health Care Workers (HCW). The studies evaluate the association between circulating SARS-CoV-2 variants and short, mid and long-term clinical outcomes. Data submitted here includes participant-level clinical variables collected as part of the EuCARE clinical cohort studies.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008578","title":"Spatial_profiling_of_human_testis_using_Xenium_and_Trencadis_Seq","description":"R&amp;D pilot to use Xenium and Trencadis-Seq for genome and transcriptome profiling of fresh-frozen human testis tissue. ","abstract":"This study will evaluate the feasibility and data quality of complementary genome and transcriptome profiling methods in human testis tissue. Fresh-frozen tissue will undergo histological assessment followed, where suitable, by Xenium spatial transcriptomic analysis and Trencadis-Seq profiling. Results will guide method development and decisions about expanding the study to additional tissue regions.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008579","title":"Oceania Genome Variation Project","description":null,"abstract":"Oceania and Island Southeast Asia have a rich, yet understudied, human genomic landscape. This region encompasses some of the first areas inhabited by humans following the out-of-Africa expansion, includes populations with the highest levels of archaic hominin introgression, and contains Pacific islands that are among the most remote continuously inhabited locations in the world. Here, we describe the first region-wide analysis of individuals from population groups spanning Oceania and its perimeter. In total we generate and analyze genome-wide data from 92 different populations, 58 separate islands, and 30 countries, covering one third of the planet. Leveraging this diverse dataset, we resolve genetic connections among islands, providing a detailed view of regional population structure and identifying the island groups involved in the settlement of several Polynesian Outliers. Ancestry-specific analyses allow us to deconvolve different layers of history, from tracing groups deriving their Austronesian ancestry via the Lapita expansion to quantifying variable archaic introgression across the basal Papuan component of Oceanians and Southeast Asians. Finally, we map biomedically relevant variants across Oceania and Southeast Asia, observing pronounced allele-frequency differences between population groups. Together, these findings refine models of oceanic settlement and admixture and establish a comprehensive reference that will advance global efforts to ensure fair and equitable representation in human genomics.","study_type":"Population Genomics","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008580","title":"CG_Multi_P_N4S_Lee_Six_Spatial_Managed","description":"Spatial analysis of children relating to N4S.","abstract":"Spatial analysis of children relating to N4S.","study_type":"Transcriptome Analysis","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008581","title":"Genome-wide DNA methylation profiling using the Illumina Infinium MethylationEPIC BeadChip array. This submission contains a subset of follicular lymphoma (FL),  diffuse large B-cell lymphoma (DLBCL), and normal B-cell reference samples.","description":"Follicular lymphoma (FL) has a highly variable clinical course, and a subset of patients experience early progression or histologic transformation to diffuse large B-cell lymphoma (DLBCL). Current prognostic models do not directly measure the extent to which an individual tumor has acquired biological features associated with transformation. We analyzed genome-wide DNA methylation profiles from 338 FL, 12 transformed FL, 145 de novo DLBCL, 20 reactive lymph nodes, and 36 normal B-cell reference samples. We derived a continuous methylation score representing each tumor's position along a spectrum from FL to DLBCL. FL tumors spanned a continuous methylation spectrum, with transformed FL occupying an intermediate position between FL and DLBCL. Within FL, higher scores were associated with greater mutation burden, enrichment of mutations in genes recurrently altered in FL, higher mitotic clock scores, and activation of proliferative and metabolic gene expression programs. Clinically, higher scores were significantly associated with a higher risk of transformation (HR 8.95, 95% CI 1.72-46.47; P = 0.009), independent of the Follicular Lymphoma International Prognostic Index. These findings demonstrate that DNA methylation captures a continuum of biological progression from FL toward DLBCL and identifies patients at increased risk of transformation.","abstract":"Follicular lymphoma (FL) has a highly variable clinical course, and a subset of patients experience early progression or histologic transformation to diffuse large B-cell lymphoma (DLBCL). Current prognostic models do not directly measure the extent to which an individual tumor has acquired biological features associated with transformation. We analyzed genome-wide DNA methylation profiles from 338 FL, 12 transformed FL, 145 de novo DLBCL, 20 reactive lymph nodes, and 36 normal B-cell reference samples. We derived a continuous methylation score representing each tumor's position along a spectrum from FL to DLBCL. FL tumors spanned a continuous methylation spectrum, with transformed FL occupying an intermediate position between FL and DLBCL. Within FL, higher scores were associated with greater mutation burden, enrichment of mutations in genes recurrently altered in FL, higher mitotic clock scores, and activation of proliferative and metabolic gene expression programs. Clinically, higher scores were significantly associated with a higher risk of transformation (HR 8.95, 95% CI 1.72-46.47; P = 0.009), independent of the Follicular Lymphoma International Prognostic Index. These findings demonstrate that DNA methylation captures a continuum of biological progression from FL toward DLBCL and identifies patients at increased risk of transformation.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS00001008582","title":"Fibroblasts confer epithelial immune priming and memory on colon organoid co-cultures","description":"Innate immune regulation at barrier organs needs to balance the effective response against pathogens with tolerance of the commensal microbiome. Myeloid cells are the main effectors of innate immunity, but many more cell types engage in innate immune signaling. Here we focus on the emerging immune-modulatory role of fibroblasts in the context of the colon’s mucosal barrier, where the exposure to a wide spectrum of microbes necessitates constant immune vigilance. We present a human organoid co-culture model that integrates colonic epithelial cells with fibroblasts but excludes myeloid and lymphoid cells, thereby allowing us to dissect native immune signaling among the non-hematopoietic cells. Our analyses uncover fibroblast-mediated immune priming of epithelial cells driven by the fibroblasts’ basal interferon production under homeostatic conditions. This immune priming provides enhanced protection against viral infection for the colon organoids, which is retained as immune memory for up to three weeks after removal of the fibroblasts. In summary, our study highlights the role of fibroblasts as mediators of immune priming and memory, both under homeostatic conditions and upon pathogen challenge; and it establishes a human organoid co-culture model for investigating immune interactions among non-hematopoietic structural cells, thereby contributing to a better understanding of stromal-epithelial crosstalk in immune homeostasis and mucosal immunity.","abstract":"Innate immune regulation at barrier organs needs to balance the effective response against pathogens with tolerance of the commensal microbiome. Myeloid cells are the main effectors of innate immunity, but many more cell types engage in innate immune signaling. Here we focus on the emerging immune-modulatory role of fibroblasts in the context of the colon’s mucosal barrier, where the exposure to a wide spectrum of microbes necessitates constant immune vigilance. We present a human organoid co-culture model that integrates colonic epithelial cells with fibroblasts but excludes myeloid and lymphoid cells, thereby allowing us to dissect native immune signaling among the non-hematopoietic cells. Our analyses uncover fibroblast-mediated immune priming of epithelial cells driven by the fibroblasts’ basal interferon production under homeostatic conditions. This immune priming provides enhanced protection against viral infection for the colon organoids, which is retained as immune memory for up to three weeks after removal of the fibroblasts. In summary, our study highlights the role of fibroblasts as mediators of immune priming and memory, both under homeostatic conditions and upon pathogen challenge; and it establishes a human organoid co-culture model for investigating immune interactions among non-hematopoietic structural cells, thereby contributing to a better understanding of stromal-epithelial crosstalk in immune homeostasis and mucosal immunity.","study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS0001000288","title":"Genentech Colon Cancer Screen","description":"Exome capture, RNA-Seq, whole genome sequencing of set of Colon Cancer samples.","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS0001000334","title":"Genentech Small Cell Lung Cancer (SCLC) Screen","description":"Genentech Colon Cancer Screen","abstract":null,"study_type":"Other","pubmed_ids":null,"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000001","title":"Age-dependent association of clonal hematopoiesis with COVID-19 mortality in patients over 60 years","description":"Genomic DNA extracted from peripheral blood of COVID-19 patients (n = 241 deceased, n = 239 survivors) was sequenced with the Myeloid Solutions™ panel of SOPHiA Genetics. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[36184726],"external_links":null,"is_released":true,"released_date":"2023-12-05T10:11:51.33797+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000003","title":"Test","description":"Test","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000005","title":"Nurminen et al (\"GP2Men\") Study Primary and Metastatic Prostate Cancer Whole Genome Sequence Data","description":"We used novel processing techniques to obtain whole genome data together with 3D anatomic and histomorphologic analysis in two men (GP5 and GP12) with high risk PrCa undergoing radical prostatectomy. A total of 22 whole genome-sequenced sites (16 primary cancer foci and 6 lymph node metastatic) were analyzed using evolutionary reconstruction tools and spatio-evolutionary models. Probability models were used to trace spatial and chronological origins of the primary tumor and metastases, chart their genetic drivers, and distinguish metastatic and non-metastatic subclones.\r\n","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-10-04T18:24:35.990952+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000006","title":"Full AfricanNeo ModernDNA Study","description":"With the largest genomic dataset to date of Bantu-speaking populations, including newly generated data of modern-day and ancient DNA from previously unsampled regions in Africa, we shed fresh light on the expansion of peoples speaking Bantu languages that started ~4000 years ago in western Africa. We have genotyped 1,763 participants, including 1,487 Bantu speakers from 143 populations across 14 African countries. Our comprehensive genetic analysis of the expansion of people speaking Bantu languages reveals a complex history of serial founder events, variable levels of contact with local groups, and spread-over-spread events.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-10-05T12:34:08.627113+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000007","title":"QuantSeq 3'-mRNAseq of pathogen-stimulated PBMCs","description":"5 donors, 4 stimuli, 2 time points","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-10-18T16:51:29.205237+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000008","title":"Breast cancer risk SNPs converge on estrogen receptor binding sites commonly shared between breast tumors to locally alter estrogen signalling output","description":"Evaluate the biology underlying inter-tumor cistromic heterogeneity of ER-alpha, in relation to genomic locations and germline variations between breast cancer tumors\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-10-16T12:12:14.323895+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000009","title":"Evaluation of the ERa binding region activity in breast and endometrial cancer","description":"Evaluate the activity of ERa binding site activity in breast and endometrial cancer.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[40494627],"external_links":null,"is_released":true,"released_date":"2023-10-19T09:40:51.827776+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000010","title":"Comprehensive NGS Profiling to Enable Detection of ALK Gene Rearrangements and MET Amplifications in Non-Small Cell Lung Cancer","description":"We evaluate the analytical performance of the PGDx™ elio™ tissue complete assay, a 505 gene next-generation sequencing (NGS) tissue-based assay, that has now been FDA-cleared for use by physicians to help guide treatment decisions for cancer patients, using a NSCLC cohort of 38 patients.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-10-10T11:55:59.777488+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000011","title":"Gene Expression Signature in Normal Mammary Gland from 83 Breast Cancer Patients Indicates Pre-tumorous Changes and Adverse Outcomes","description":"This study assessed the transcriptomic profiles of 242 samples from 83 breast cancer patients with\r\nunfavorable outcomes, including paired uninvolved mammary gland samples collected at varying\r\ndistances from primary lesions. As a reference, control samples from 53 mammoplasty individuals\r\nwithout cancer history were studied. A custom panel of 634 genes linked to breast cancer progression\r\nand metastasis was employed for expression profiling (targeted RNA sequencing), followed by whole-transcriptome (RNA sequencing) verification\r\nexperiments and statistical analyses to discern molecular signatures and their clinical relevance.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[38850108],"external_links":null,"is_released":true,"released_date":"2025-02-18T18:28:51.396515+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000012","title":"Systemic Lupus Erythematosus Serum Stimulation of Human Intestinal Organoids Induces Barrier Leakiness and Changes in Goblet Cell Differentiation","description":"Human intestinal epithelial cells are the interface between potentially harmful luminal content and basally residing immune cells. Their role is not only nutrient absorption but also the formation of a tight monolayer that constantly secretes mucus creating a multi-layered protective barrier. Alterations in this barrier can lead to increased gut permeability which is frequently seen in individuals with chronic extraintestinal autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). Despite recent advances in identifying alterations in gut microbiota composition in SLE patients, not much attention has been given to the epithelial barrier itself. To date, it remains largely unexplored which role and function intestinal epithelial cells have in SLE pathology. Here, we present a unique near-physiologic in vitro model specifically designed to examine the effects of SLE on the epithelial cells. We utilize human colon organoids that are stimulated with serum obtained from SLE patients. Combining bulk and single-cell RNA transcriptomic analysis with functional assays revealed that SLE serum stimulation induced a unique expression profile marked by a reduction of goblet cell marker expression and mucus composition. Additionally, organoids exhibited imbalanced cellulat composition along with enhanced paracellular permeability,mitochondrial function, and a type I interferon gene signature. Similarly, transcriptomic analysis of SLE human colon biopsies revealed a downregulation of epithelial secretory markers. Our work uncovers a crucial connection between SLE and intestinal homeostasis that might be promoted in vivo through the blood, offering insights into the causal connection of barrier dysfunction and autoimmune diseases.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000013","title":"Transcriptome Sequencing PPGL (2)","description":"RNA-Seq data (n=81) library preparation was performed as previously reported by Calsina et al 2023 using QuantSeq 3' mRNA-Seq Library Prep Kit FWD for Illumina (Lexogen, 015). The prepared libraries were subsequently sequenced on NovaSeq™ system (Illumina). To combine the new CNIO samples (n=81) with the CNIO+TCGA dataset generated in Calsina et al., 2023, RNA data were processed using ComBat-seq as described in that same article. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-30T14:42:41.672918+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000014","title":"Transcriptional Reference Map of Human Natural Killler Cells","description":"Here we performed single-cell RNA sequencing of both bulk NK and sorted NK subsets to establish a transcriptional reference map of human natural killer cells. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-10-26T18:13:18.617546+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000015","title":"Efficacy of two different FGFR-inhibitors in a patient with extrahepatic cholangiocarcinoma harboring an FGFR2 mutation","description":"Cholangiocarcinomas (CCAs) is a type of cancer with few effective systemic therapies. Elucidation of the molecular landscape of the disease from genomic studies based on next generation sequencing (NGS) has contributed to the introduction of new targeted therapies. One of these treatments consists of a class of small molecules that target members of the FGFR family of receptor tyrosine kinases. These drugs are effective and have been approved for cholangiocarcinomas with fusions or rearrangements of FGFR genes. In contrast, the role of these inhibitors in cholangiocarcinomas with mutations in FGFR genes is less well defined. We report here a patient with a cholangiocarcinoma bearing a FGFR2 p.Ser252Trp mutation. The patient was treated with two different FGFR inhibitors, as the first caused ocular toxicity. She obtained clinical benefit from both. This case illustrates the efficacy of FGFR inhibitors on cholangiocarcinoma with specific point mutations. This is the first case to report the clinical benefit of these drugs in FGFR2 p.Ser252Trp mutation. Clinical benefit can be sustained, as seen in our patient. Our case also shows that FGFR inhibitors-induced adverse effects, such as ocular toxicities, may not recur after re-challenge with an alternative drug of the same class.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-10-19T15:21:36.050174+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000016","title":"The genomic basis of childhood T-lineage acute lymphoblastic leukemia","description":"T-lineage acute lymphoblastic leukemia (T-ALL) is a high-risk tumor that has eluded comprehensive genomic characterization, in part due to the high frequency of non-coding genomic alterations resulting in oncogenic dysregulation. Here we report integrated genome and transcriptome sequencing of T-ALL tumor and remission samples obtained from over 1300 uniformly treated children with T-ALL, coupled with epigenomic and single cell analysis of malignant and normal T cell precursors. Integrated analysis identified 15 subtypes with distinct genomic drivers, gene expression, developmental state and outcome. Integration with chromatin topology analyses enabled elucidation of multiple mechanisms of enhancer deregulation that involve enhancers and genes in a subtype-specific fashion. We show that the immunophenotypically-described, high-risk entity of early T-cell precursor ALL is superseded by a broader category of leukemias of variable immunophenotype with diverse genomic alterations of a core set of genes encoding regulators of hematopoietic stem cell development. Numerous genetic alterations and disease subtypes emerged as independent predictors of survival and treatment failure in univariable and multivariable outcome models. These findings provide a roadmap for the classification, risk stratification and mechanistic understanding of this disease.\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-07T17:41:17.117025+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000017","title":"FEGA test","description":"testing the FEGA submnission workflow","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000018","title":"Identification and targeting of extremely high-risk gamma delta T-ALL in children","description":"Acute lymphoblastic leukemia expressing the gamma delta T cell receptor (γδ T-ALL) is an uncommon, poorly understood disease. We studied 200 pediatric γδ T-ALL enrolled on clinical trials to understand the clinical and genetic features of this disease, which showed variation in outcome according to age and genetic driver. γδ T-ALL diagnosed in children under three years of age was extremely high-risk and enriched for genetic alterations leading to both LMO2 activation and STAG2 inactivation. Using patient samples and isogenic cell lines, we show that inactivation of STAG2 profoundly perturbs chromatin organization by altering enhancer-promoter looping and results in deregulation of gene expression related to T-cell differentiation. High throughput drug screening identified a vulnerability in DNA repair pathways arising from STAG2 inactivation, which was efficaciously targeted by PARP inhibition. These data provide a diagnostic and therapeutic framework for classification and risk stratification of pediatric γδ T-ALL.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-11T11:28:01.953345+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000019","title":"BAM files of mapped reads from scDNAsequencing","description":"scDNAseq at low coverage of samples with different levels of ploidy: Low, High, Near and diploid (normal) plus a pool of Healthy HSPCs cells","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-11-07T14:14:15.517334+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000020","title":"Single-cell somatic copy number variants in brain using different amplification methods and reference genomes","description":"Low coverage paired end Illumina WGS from cells amplified with Picoplex, PTA, and droplet MDA. Two brains with Multiple System, Atrophy, one control, and non-brain controls (fibroblasts, NA12878)","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-12-27T12:59:38.666207+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000021","title":"A tumor focused approach to resolving the etiology of DNA mismatch repair deficient tumors classified as suspected Lynch syndrome","description":"Routine screening of tumors for DNA mismatch repair (MMR) deficiency (dMMR) in colorectal (CRC), endometrial (EC) and sebaceous skin (SST) tumors leads to a significant proportion of unresolved cases classified as suspected Lynch syndrome (SLS).  A tumor-focused testing approach reclassified 86.9% of SLS into Lynch syndrome, sporadic dMMR or MMR-proficient cases. These findings support the incorporation of tumor sequencing and alternate MLH1 methylation assays into clinical diagnostics to reduce the number of SLS patients and provide more appropriate surveillance and screening recommendations.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[37101184],"external_links":null,"is_released":true,"released_date":"2023-11-08T17:52:10.201664+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000022","title":"BRCA1 secondary splice-site mutations","description":"BRCA1 splice isoforms d11 and d11q can contribute to PARP inhibitor (PARPi) resistance by splicing-out mutation-containing exons, producing truncated, partially-functional proteins. However, the clinical impact and underlying drivers of BRCA1 exon skipping remain undetermined.\r\nWe analyzed nine ovarian and breast cancer patient derived xenografts (PDX) with BRCA1 exon 11 frameshift mutations for splice isoform expression and therapy response.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-02T11:17:46.301652+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000023","title":"The chemotherapeutic CX-5461 is extremely mutagenic and may increase cancer risk","description":"The chemotherapeutic agent CX-5461 or pidnarulex has been fast-tracked by the US FDA for treatment of BRCA1-, BRCA2-, and PALB2-mutated cancers. It is under investigation in Phase I/II clinical trials. Here we find that although CX-5461 exhibits synthetic lethality in BRCA1-/BRCA2-deficient cells, it also causes extensive, non-selective, collateral mutagenesis in all cells, to magnitudes that exceed known environmental carcinogens, raising public health concerns regarding its potential for promoting secondary cancers.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-11-15T16:45:10.675185+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000024","title":"A comprehensive genetic map of cytokine responses in Lyme borreliosis","description":"A study on the genetic determinants of immune response in patients diagnosed with Lyme borreliosis. Examining the link between genetic variants and cytokine response in more than 1,000 patients. ","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-14T17:13:32.896705+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000025","title":"Whole genome sequencing of Sinonasal hemangiopericytoma and patient derived cell line model","description":"Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) is a rare subtype of soft tissue sarcoma associated with NAB2-STAT6 gene fusions. This study established and characterized a novel SFT/HPC patient-derived cell line called SFT-S1 using whole genome sequencing.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-11-08T17:48:11.971415+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000026","title":"Methylome profiling of Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) and a patient derived cell-line model","description":"Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) is a rare subtype of soft tissue sarcoma associated with NAB2-STAT6 gene fusions. This study established and characterized a novel SFT/HPC patient-derived cell line called SFT-S1 using the twist human methylome panel.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-11-08T17:48:02.169599+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000027","title":"Evaluating potential drug candidates for the treament of Henamgiopericytoma on patient derived cell line models","description":"Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) is a rare subtype of soft tissue sarcoma associated with NAB2-STAT6 gene fusions. This study established and characterized a novel SFT/HPC patient-derived cell line called SFT-S1. Potential drug candidates that could be repurposed for the treatment of SFT/HPC were screened.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-11-08T17:48:05.826686+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000028","title":"Male breast cancer","description":"Male breast cancer (MBC) samples from PRONON to identify novel MBC\r\npredisposition genes through germline whole-exome sequencing in a total of 30\r\nunrelated Brazilian men with breast cancer, negative to BRCA1/BRCA2 germline\r\nPathogenic variants, and unselected for family history.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000029","title":"Human Brain Small Extracellular Vesicles Contain Selectively-Packaged, Full-Length mRNA","description":"Brain cells release and take up small extracellular vesicles (sEVs) containing bioactive nucleic acids. sEV exchange is hypothesized to contribute to stereotyped spread of neuropathological changes in the diseased brain. We assessed mRNA from sEVs of non-diseased (ND) and Alzheimer’s disease (AD) human postmortem brain, using short- and long-read sequencing.  sEV transcriptomes were distinct from bulk tissue, showing enrichment for multiple genes including mRNAs encoding ribosomal proteins and L1Hs transposable elements. AD versus ND sEVs showed enrichment of inflammation-related and depletion of synaptic signaling mRNAs. sEV mRNA from cultured murine primary neurons, astrocytes, or microglia showed similarities with human brain sEVs and revealed cell-type specific packaging. Nearly 80% of human brain sEV transcripts sequenced using long-read sequencing were full-length. Motif analyses of sEV-enriched full-length isoforms revealed RNA-binding proteins that may be associated with sEV loading.  Collectively, we show that mRNA in brain sEVs is selectively-packaged and altered by disease state.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-04T16:04:04.12213+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000030","title":"Multiomic spatial landscape of innate immune cells at central nervous system borders ","description":"The innate immune compartment of the human central nervous system (CNS) is highly diverseand includes several immune cell populations such as macrophages that are frequent in the brain parenchyma (microglia) and less numerous at the brain interfaces as CNS-associated macrophages (CAMs).Due to their scantiness and particular location, little is known about the presence of temporally and spatially restricted CAM subclasses during development, health and perturbation. Here, we combined single-cell RNA-sequencing, time-of-flight mass cytometry and single-cell spatial transcriptomics with fate mapping and advanced immunohistochemistry to comprehensively characterize the immune system at human CNS interfaces. We also provide a comprehensive analysis of resident and engrafted myeloid cells in the brains of 15 individuals with peripheral blood stem cell transplantation, revealing compartment-specific engraftment rates across different CNS interfaces... Our results highlight myeloid diversity at the interfaces of the human CNS with the periphery and provide insights into the complexities of the human brain’s immune system.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-11-08T17:30:50.814479+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000031","title":"Whole-exome sequencing data of ovarian clear cell carcinoma in East Asia","description":"This is a genomic study to uncover the molecular landscape of ovarian clear cell carcinoma (OCCC) in East Asia. This dataset contains normal-tumor paired samples of 104 patients with OCCC diagnosed in two branches of Chang Gung Memorial Hospital, Taiwan. These are paired-end, whole-exome sequencing data, sequenced by Illumina NovaSeq with target depth of 150X. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-11-15T17:12:04.390355+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000032","title":"Tumor Evolution Analysis Uncovered Immune-Escape  Related Mutations in Relapsed Diffuse Large B-Cell Lymphoma","description":"More than 60% of patients with primary diffuse large B-cell lymphoma (DLBCL) achieve durable remissions upon the chemoimmunotherapy with R-CHOP. However, the outcome of the relapse patients is extremely poor. To characterize the molecular features that underlie treatment resistance, we performed whole-exome sequencing (n=44) and deep targeted sequencing (n=27) of 44 diagnosis-relapse DLBCL pairs. We found that the overall landscape of genetic alterations was concordant between diagnosis and relapse DLBCL. By a deep comparison of the longitudinal sequencings, we identified relapse-enriched mutations that involved in evasion of immune surveillance (CD58, TNFRSF14, PKD1, FAS), resistance to DNA damaging agents (ATM, TP53), and critical tumor suppressor gene (ZFHX3). Knockdown of ATM and ZFHX3 resulted in increased drug resistance in both germinal center B cell like (GCB) and activated B cell like (ABC) DLBCL cell lines in vitro, while the knockdown of TNFRSF14 and FAS conferred resistance specifically in GCB cell lines. Furthermore, we summarized two evolutionary patterns of DLBCL relapse as the “durable retention” model with stable clone structure, and the “selective sweep”  model which exhibited significant clonal switch. Of note, genetic alterations leading to attenuated immune responses usually presented as trunk mutations in the “durable retention” model (7/12) while were newly acquired or expanded upon relapse in the “selective sweep” model (9/16). Overall, our study demonstrated that relapse DLBCL derives from distinct clonal evolutionary patterns, and highlighted immune escape as an important contributor of tumor relapse.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-18T16:53:14.079328+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000033","title":"Papua New Guinean Lowlanders Dataset","description":"High-coverage whole genome sequences were collected to study patterns of genomic\r\nvariation across the southern lowland of Papua New Guinea. This region has experienced an\r\nextremely complex demographic history, including repeated bouts of admixture with\r\narchaic and modern human groups. This dataset reports whole genome sequences for 41\r\nindividuals from this region. Particular attention has been paid in the original study to\r\ngenomic signals that are informative for population history, including admixture with\r\narchaic hominins and the role of modern human admixture during the late Pleistocene and\r\nHolocene.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[38688933],"external_links":null,"is_released":true,"released_date":"2024-04-11T14:20:22.250332+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000034","title":"single cell transcriptomic analysis of tumor samples collected from 5 patients with EMM","description":"Contains the raw single cell RNAseq data used for the study","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-02T12:08:26.616116+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000035","title":"Bulk RNAseq of patient samlpes at the stage of NDMM, RRMM without EMM and EMM","description":"This study contains the raw bulk RNAseq data used for the publication","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-02T12:08:22.307064+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000036","title":"WES data from patient samples at the stage of NDMM and EMM and normal samples ","description":"This contains the raw Whole Exome sequencing data used for the publication","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-02T12:08:24.55724+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000037","title":"Single-cell profiling reveals mechanisms of response to anti-PD-L1 versus anti-PD-L1 combined with anti-CTLA4 in head and neck squamous cell carcinoma","description":"Cancer patients often receive a combination of PD-(L)1 and CTLA4 inhibitors, but the mechanisms underlying their concerted actions remain unclear. We conducted a neoadjuvant study in head and neck squamous cell carcinoma (HNSCC) involving anti-PD-L1 monotherapy versus anti-PD-L1/anti-CTLA4 combination. Single-cell profiling of on- versus pre-treatment biopsies confirmed T-cell expansion as response biomarker. We identified a type 1 immune response accompanying T-cell expansion on-treatment across treatment arms, and herein characterized co-localized IgG plasma cell expansion as important contributor. In pre-treatment biopsies, similar features correlated with expansion upon anti-PD-L1, but not anti-PD-L1/anti-CTLA4. By profiling tumor-draining lymph nodes, we found the addition of anti-CTLA4 to trigger activation and subsequent trafficking of CD4+ T-cells via the blood, to become T-helper 1 cells in the tumor. anti-PD-L1/anti-CTLA4 indeed facilitated co-localized expansion of CD4+ and CD8+ T-cells in tumors versus mostly CD8+ T-cells with anti-PD-L1 alone. Hence, we identify complimentary mechanisms underlying anti-PD-L1/anti-CTLA4 therapy in HNSCC.\r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-06T16:56:37.017288+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000038","title":"The Dynamic Immune Behavior of Primary and Metastatic Ovarian Carcinoma","description":"Patients with high-grade serous ovarian carcinoma are usually diagnosed at an advanced stage and often develop resistance to conventional therapy. Epithelial ovarian tumors have been shown to be rich in CD8+ lymphocytes, which infiltrate both primary and omental sites. In recent years, several prominent studies have highlighted a positive association between the presence of these immune cells and a good prognosis; however, clinical trials of immune checkpoint inhibitors have so far shown unsatisfactory results in ovarian cancer. In this study, we used an innovative combination of single-cell sequencing and spatial transcriptomics to identify the molecular mechanisms that lead to immunosuppression in primary and metastatic HGSC. Primary tumors consistently showed a more active immune microenvironment than did omental tumors. In addition, while several immune cell subtypes were present in all samples, their relative abundance differed between primary and omental tumors. Finally, we found that primary tumors were mostly populated by dysfunctional CD4 and CD8 T cells in later stages of differentiation, while omental tumors were mostly populated by naïve immune cells; this, in turn, was correlated with expression changes in the interferon α and γ pathways in epithelial cells, showing that cross-communication between the epithelial and immune compartments is important for immune suppression in ovarian cancer. These findings can impact the timing and choice of immune-modulating drugs and should be considered when planning treatment for patients with high-grade serous ovarian carcinoma. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-13T16:26:05.374966+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000039","title":"Epigenomic dataset of Human Hepatocellular Carcinoma for EpiHK","description":"This dataset is generated for EpiHK. It contains Histone PTM ChIP-seq, WGBS, RNA-seq of Human Hepatocellular Carcinoma and tumor adjacent normal tissue sample. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-28T14:30:24.495674+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000040","title":"Metabolic and molecular consequences of the TBC1D4 p.Arg684Ter variant in human skeletal muscle","description":"Skeletal muscle of Inuit homozygous carriers of the common Greenlandic TBC1D4 p.Arg684Ter variant is severely insulin resistant but have normal metabolic responses during exercise,","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-22T11:56:09.832034+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000041","title":"ABCB1 expression in HCC biopsies","description":"We analyzed the ABCB1 expression in RNA-seq data of 134 HCCs (120 of these were previously published), including the biopsies from which the 3 doxorubicin-sensitive and 3 doxorubicin-resistant HCCOs were derived. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[35508466],"external_links":null,"is_released":true,"released_date":"2024-04-19T10:04:20.039995+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000042","title":"Transcriptome HCCO Hypoxia and Doxorubicin resistance","description":"We hypothesized that HCCO-intrinsic determinants of response to hypoxia or doxorubicin could be reflected in the gene expression profiles of the HCCOs. Therefore, we selected for comparative transcriptomic analysis two sets of 4 HCCO lines that were severely (hypoxia-sensitive) or barely affected (hypoxia-resistant) by hypoxia in an ATP-based proliferation assay or two sets of 4 HCCO lines whose doxorubicin response curves were clearly separated both under normoxic and hypoxic culture conditions for comparative transcriptomic analysis.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-19T10:04:20.039995+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000043","title":"WES in HCCOs with varying Doxorubicin resistance","description":"We aimed to identify somatic mutations that could explain the resistance to Doxorubicin. Therefor, we purified Exomes from liver biopsies and HCC organoids using Agilent SureSelectXT (clinical research exome, HS2 V8, or Human all Exon V6 Cosmic) and performed WES. Matched non-tumoral liver biopsies served as the control for germline mutations. 12 of these samples were previously reported. \r\nSequence reads were aligned to the reference human genome GRCh38 using Burrows-Wheeler Aligner (BWA, v0.7.17). Duplicate removal, base quality adjustment, mutation calling (Mutect2, intervals: SureSelectXT_HS_V8_S33266340, germline-recourse: gnomad.exomes.r2.1.1.sites.liftover_grch38, Panel-of-Normal: 1000g_pon.hg38), filtering of Mutect calls, and functional annotation (Funcotator, funcotator_dataSources.v1.7.20200521g) were performed using the Genome Analysis Toolkit (GATK, v4.4) according to the Broad Institute best practices in Somatic short variant discovery workflows. \r\nMutations with a functional annotation of Deletion, Insertion, Non-stop, Splice-Site, Start-Codon and Missense mutations were kept.  A list of 43 commonly mutated genes in HCC was analyzed in the HCC organoids [TCGA, Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma. Cell, 2017. 169(7): p. 1327-1341.e23].\r\n","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[35508466],"external_links":null,"is_released":true,"released_date":"2024-04-19T10:04:20.039995+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000044","title":"SNP Genotype Data: Subpopulations of Filipino, Malaysian, and Papua New Guinea","description":"In the context of the study 'Exploring Adaptive Phenotypes for the Human Calcium-Sensing Receptor Polymorphism R990G,' this repository contains 11 VCF files. Each file includes genetic data from 22 autosomes, representing distinct subpopulations.\r\n\r\nThe subpopulations are as follows:\r\n\r\nMalaysian:\r\n\r\n    Aeta (15 samples)\r\n    Agta (11 samples)\r\n    Batak (10 samples)\r\n    Mamanwa (6 samples)\r\n\r\nFilipino:\r\n\r\n    Jehai (13 samples)\r\n    Kintaq (6 samples)\r\n    Temiar (5 samples)\r\n\r\nPapua New Guinea:\r\n\r\n    Highlands (2 samples)\r\n    Koinambe (10 samples)\r\n    Kosipe (10 samples)\r\n    Sepik (2 samples)\r\n\r\nThe numbers in parentheses indicate the sample size for each respective subpopulation.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000045","title":"SARS-CoV2 mRNA-vaccination-induced Immunological Memory in Human Non-Lymphoid and Lymphoid Tissues","description":"SARS-CoV2 mRNA vaccination-induced CD4+ Th cells were isolated based on activation marker expression from human bone marrow (n=3), lung (n=5), liver (n=4) and paired blood samples (to liver donors, n=4) of virus-naive vaccinees after Spike peptide mix stimulation in vitro. The 10X platform was used for single cell transcriptome analysis, along with T cell receptor clonotype analysis in a total of 1985 cells. Samples were sequenced on a NovaSeq 6000 (Illumina).","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-11-23T19:23:22.083167+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000046","title":"Differential gene expression in the colon mucosa of irritable bowel syndrome patients with diarrhea-predominant symptoms","description":"The aim of this study is to characterize the pathophysiology of the irritable bowel syndrome (IBS) on the functional level and in parallel on the gene expression level. For this purpose RNAseq of mucosal biopsies was performed. The data from the differential expression analysis will be further processed by Ingenuity Pathway Analysis (IPA) software to gather Information on activated or inhibited signaling pathways in the disease.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-05T11:31:20.579453+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000047","title":"RNAseq and ATACseq on HGSC lines, pre- and post-treatment with an epigenetic drug","description":"This study looked to determine changes in gene expression and chromatin accessibility of five HGSC cell lines, following treatment with a novel epigenetic drug. The epigenetic drug, HKMTi-1-005, is a compound with dual activity against H3K27 and H3K9 methylation. The cell lines used were PEO1, PEO4, PEA2, OVCAR5, OVCAR8.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-12-12T11:14:17.161612+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000048","title":"Whole exome sequencing of pediatric soft tissue sarcoma PDX models ","description":"Childhood cancer remains one of the leading causes of death in pediatric patients in Europe. Pediatric sarcomas, comprising soft tissue sarcomas and malignant bone tumors, are a heterogenous group of malignancies, with more than 50 subtypes (WHO classification). Due to low case numbers,  studying pediatric sarcomas requires accurate and reliable preclinical models. Here, we established 18 soft tissues sarcoma PDX models, including Ewing Sarcoma, Rhabdmyosarcoma and Osteosarcoma. We characterized these models by Whole Exome Sequencing and assessd the response to a wide range of drugs.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-12-12T09:41:15.15815+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000049","title":"NGS on cardiac samples in Hungarian patients of dilated cardiomyopathy ","description":"Heterozygous (HET) truncating mutations in the TTN gene (TTNtv) encoding the giant titin protein are the most common genetic cause of dilated cardiomyopathy (DCM). We investigated 127 clinically identified DCM human cardiac samples with targeted sequencing using the TruSight Cardio panel on an Illumina MiSeq system with a special focus on TTNtvs.","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-11-15T17:13:14.811701+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000050","title":"Single cell RNA sequencing of multiple myeloma patient and healthy donors","description":"This study includes 48 single cell RNA sequencing samples of 24 multiple myeloma patients and 5 healthy donors forming a control group generated with the 10x Genomics platform. For the multiple myeloma patient, bone marrow (n=23) or pleural effusion (n=1) mononuclear cells were cultured overnight with or without BH3 mimetics combination. Libraries were sequenced on NovaSeq 6000 to a\r\nmean depth of 45,000 reads/cell as paired-end, 28bp Read 1, 90bp Read 2 (GenoA, UMS\r\nBiocore, SFR Bonamy, Nantes)\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000051","title":"Dataset of DNA methylation profiles of 189 pediatric central nervous system, soft tissue, and bone tumors","description":"The research of CNS tumors brought knowledge about the role of epigenetics in these tumors. Certain subgroups of tumors are defined solely by their epigenetic profiles. In this study we carried on epigenetic profiling using targeted methylation sequencing of aproximately 180 pediatric CNS and Sarcoma tumor samples. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-11-27T16:01:21.377323+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000052","title":"Multimodal epigenetic sequencing analysis for colon cancer","description":"Targeted methylation sequencing (enzymatic conversion) data of plasma samples collected from colon cancer patients and non-cancer subjects.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-12-05T14:46:11.368945+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000053","title":"Long-read-transcriptome-sequencing of CLL and MDS patients uncovers common molecular effects of SF3B1 mutations","description":"Mutations in SF3B1 occur frequently in patients with chronic lymphocytic leukemia (CLL) and myelodysplastic syndromes (MDS), and a full-length transcriptome approach can expand our current knowledge on SF3B1 mutation effects on RNA splicing. We applied long-read-transcriptome-sequencing (LRTS) to 44 MDS and CLL patients with and without SF3B1 mutations and found a large fraction (>60%) of novel isoforms. Furthermore, we revealed that mutation effects on alternative splicing were largely common in both cancer types and specifically altered the usage of introns as well as 3’-splice-sites. We combined the LRTS with genome-wide SF3B1-RNA binding maps and show multimodal binding at 3’-splice-sites highlighting a window of 12-21nt upstream of the canonical 3’-splice-site in which a dynamic switch in splice site usage is observable in patients carrying SF3B1 mutations. Our work presents the hitherto most complete LRTS study in CLL and MDS and provides a resource for further research on aberrant splicing in cancer.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[39271291],"external_links":null,"is_released":true,"released_date":"2024-08-21T16:08:00.112779+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000054","title":"Duplex sequencing","description":"A total of 387 buccal swab samples were subjected to error-corrected sequencing (duplex sequencing).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-11-22T14:01:23.930035+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000055","title":"Whole-exome sequencing","description":"Buccal mucosal remodelling was evaluated through whole-exome sequencing on 40 samples of 0.2mm^2 in size from a subject.\r\nA paired control sample was also sequenced.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-11-27T17:41:15.227971+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000056","title":"Recording physiological history of cells with chemical labeling.","description":"Recordings of the physiological history of cells provide insights into biological processes, yet obtaining such recordings is a challenge. To address this, we introduce a method to record transient cellular events for later analysis. We designed proteins that become labeled in the presence of both a specific cellular activity and a fluorescent substrate. The recording period is set by the presence of the substrate, whereas the cellular activity controls the degree of the labeling. The use of distinguishable substrates enabled the recording of successive periods of activity. We recorded protein-protein interactions, G-protein-coupled receptor activation and elevations in intracellular calcium. Recordings of elevated calcium levels allowed selections of cells from heterogenous populations for transcriptomic analysis and tracking of neuronal activities in flies and zebrafish.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-11-20T16:30:04.57061+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000057","title":"H3K27ac ChIP-seq of lung neuroendocrine tumors","description":"H3K27ac ChIP-seq of lung neuroendocrine tumors","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-16T12:54:12.313474+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000058","title":"RNA-seq of lung neuroendocrine tumors","description":"RNA-seq of lung neuroendocrine tumors","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-16T12:54:12.313474+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000059","title":"Colon cancer targeted sequencing study contaning WBCs, primary tumor tissue and plasma samples","description":"In the setting of localized colon cancer (CC), circulating tumor DNA (ctDNA) monitoring in plasma has shown potential for detecting minimal residual disease (MRD) and predicting higher risk of recurrence. With the tumor-only sequencing approach, however, germline variants may be misidentified as somatic variations, precluding the possibility of tracking in up to 11% of patients due to a lack of known somatic mutations. In this study comprising 148 prospectively recruited localized CC patients, a custom 29-gene panel was utilized to sequence both tumor tissue and matched white blood cells (WBCs) to enhance the accuracy of sequencing results. Performing targeted sequencing of paired tumor tissue and WBCs samples detected additional somatic mutations and increased the number of patients eligible for MRD tracking in plasma, although MRD detection sensitivity was not increased. Furthermore, the germline testing approach revealed the presence of pathogenic germline variants, thereby helping identify patients at elevated risk of hereditary cancer syndromes. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-11-22T14:19:24.135563+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000060","title":"Cerebrospinal fluid cfDNA sequencing for classification of central nervous system glioma","description":"Primary central nervous system (CNS) gliomas can be classified by characteristic genetic alterations. In addition to solid tissue obtained by surgery or biopsy, cell-free DNA (cfDNA) derived from cerebrospinal fluid (CSF) is an alternative source of material for genomic analyses. \r\nExperimental design: We performed targeted next-generation sequencing (NGS) of CSF cfDNA in a representative cohort of 85 patients presenting with with suspicion of primary or recurrent glioma at two neurooncological centers. Copy-number variation (CNV) profiles, single nucleotide variants (SNVs), and small insertions/ deletions (indels) were combined into a molecular-guided tumor classification. Comparison with the solid tumor was performed for 38 cases with matching solid tissue available. \r\nResults: Cases were stratified into four groups: glioblastoma (n = 32), other glioma (n = 19), non-malignant (n = 17) and no confirmed diagnosis available (n = 17). We introduce a molecular-guided tumor classification, enabling identification of tumor entities and/ or cancer specific alterations in 75.0 % (n = 24) of glioblastoma and 52.6 % (n = 10) of other glioma cases. The overlap between CSF and matching solid tissue was highest for CNVs (26-48 %) and SNVs at pre-defined gene loci (44 %), followed by SNVs/indels identified via uninformed variant calling (8-14 %). A molecular-guided tumor classification was made 23.5 % (n = 4) of cases with no confirmed diagnosis available.\r\nConclusions: We developed a workflow for targeted sequencing of CSF cfDNA as well as a strategy for interpretation and reporting of sequencing results based on a molecular-guided tumor classification in glioma.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-12-19T12:43:29.361933+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000061","title":"Identification of germline variants in Medullary thyroid carcinoma (MTC) by whole- exome sequencing","description":"Medullary thyroid cancer (MTC) is a rare malignant tumor that arises from parafollicular cells. Approximately 8% of thyroid cancer cases are MTC, and about 25% of these have a hereditary component. Incorporating molecular parameters into tumor classification is important. Besides, the presence of pathogenic germline variants can impact directly on cancer prevention. Thus, the aim of this study was to perform whole exome sequencing (WES) on a consecutive series of hereditary RET wild-type MTC patients to identify genetic variants that may be involved in the carcinogenesis of this tumor. WES was performed on 28 patients negative for germline RET pathogenic variants using the NovaSeq 6000 platform. Variant classification followed American College of Medical Genetics and Genomics guidelines.Our study represents a significant advancement in gene discovery for MTC genetics.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-05T15:39:36.67951+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000062","title":"Lipomatous tumors with 12q amplification","description":"The project concerns whole genome sequencing (short-read and long-read) and RNA-sequencing of lipomatous tumors with 12q-amplification. A subset of lipomatous tumors is driven by amplification of genes mapping to chromosome arm 12q, including the MDM2 gene. The goals of the study were to compare expression levels of genes mapping to 12q in tumors with amplification in rod-shaped or circularized chromosomes as well as to assess and compare the structural variants in those tumors. In total, 20 samples were analyzed, and the data were correlated with genomic data on bulk and single cell DNA from the same tumors. The fastq files from the tumors were uploaded to EGA.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-01T13:08:23.336138+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000063","title":"Lactate metabolism in cancer stem cell fate regulation","description":"Tumors arise as a result of uncontrolled cell proliferation driven by mutations in the signaling pathways that regulate the balance between cell division and differentiation. Despite of that, in the tumor, cancer stem cells seem to retain their capability to differentiate, which can lead to differential chemotherapy response. We previously showed that intestinal stem cells and differentiated cells display specific metabolic features and that they interact through metabolites. Moreover, we found that altering mitochondrial metabolism is sufficient to lead and define stem cell differentiation. In cancer, cellular metabolism is highly derailed. However, how metabolic changes in the cancer cell contribute to cell fate decisions remains unknown. Recently, the crosstalk between metabolism and epigenetics has emerged as one of the players in tumor development. Here we aim to address the impact of the altered metabolism of cancer cells on their epigenome as a regulatory axis of cell identity and fate. We use human-derived tumor organoids where we introduce genetic encoded fluorescent-based reporters to visualize cell identity and metabolism at single cell level. We combine 4D live imaging with a recently developed machine learning method to re-construct cell-lineages, trace stem cell state and metabolic changes during tumor organoid development. We find that, mimicking the tumor metabolic microenvironment (Warburg effect-driven low-glucose high-lactate) leads to changes cellular metabolism and histone acetylation. Strikingly, these alterations provoke profound changes in tumor development by increasing the population of cancer stem cells and their proliferation and differentiation dynamics. \r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-12T11:50:40.782836+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000064","title":"Idiopathic Collapsing Glomerulopathy in Brazilian patients","description":"Collapsing glomerulopathy is a severe kidney disease that often leads to chronic dialysis or kidney\r\ntransplantation. To expand its understanding, we performed a broad clinical and genetic analysis of a\r\nhighly admixed patient population with idiopathic collapsing glomerulopathy.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-11-29T12:24:28.061422+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000065","title":"MediMer: A versatile do-it-yourself peptide-receptive MHC class I  multimer platform for tumor neoantigen-specific T cell detection ","description":"Peptide-loaded MHC class  I (pMHC-I)  multimers have revolutionized our capabilities to monitor  \r\ndisease-associated T cell responses with high sensitivity and specificity. To improve the discovery of T \r\ncell  receptors  (TCR)  targeting  neoantigens  of  individual  tumor  patients  with  recombinant  MHC \r\nmolecules, we developed a peptide-loadable MHC class I platform termed MediMer. MediMers are \r\nbased on soluble disulfide-stabilized β2-microglobulin/heavy chain ectodomain single-chain dimers \r\n(dsSCD) that can be easily produced in large quantities in eukaryotic cells and tailored to individual \r\npatients’ HLA allotypes with only little hands-on time. Upon transient expression in CHO-S cells \r\ntogether with ER-targeted BirA biotin ligase, biotinylated dsSCD are purified from the cell supernatant \r\nand are ready to use. We show that CHO-produced dsSCD are free of endogenous peptide ligands. \r\nEmpty dsSCD from more than 30 different HLA-A,B,C allotypes, that were produced and validated so \r\nfar,  can  be loaded  with synthetic  peptides  matching  the  known  binding  criteria  of the  respective \r\nallotypes, and stored at low temperature without loss of binding activity. We demonstrate the usability \r\nof peptide-loaded dsSCD multimers for the detection of human antigen-specific T cells with comparable \r\nsensitivities as multimers generated with peptide-tethered β2m-HLA heavy chain single-chain trimers \r\n(SCT) and wild-type peptide-MHC-I complexes prior formed in small-scale refolding reactions. Using \r\nallotype-specific, fluorophore-labeled competitor peptides, we present a novel dsSCD-based peptide \r\nbinding assay capable of interrogating large libraries of in silico predicted neoepitope peptides by flow \r\ncytometry in a high-throughput and rapid format. We discovered rare T cell populations with specificity \r\nfor tumor neoepitopes and epitopes from shared tumor-associated antigens in peripheral blood of a \r\nmelanoma patient including a so far unreported HLA-C*08:02-restricted NY-ESO-1-specific CD8+ T \r\ncell population. Two representative TCR of this T cell population, which could be of potential value for \r\na broader spectrum of patients, were identified by dsSCD-guided single-cell sequencing and were \r\nvalidated by cognate pMHC-I multimer staining and functional responses to autologous peptide-pulsed \r\nantigen presenting cells. By deploying the novel CHO producer cell-based dsSCD MHC-I MediMer \r\nplatform, we hope to significantly improve success rates for the discovery of personalized neoepitope-\r\nspecific TCR in the future by being able to also cover rare HLA allotypes.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-12-15T16:09:25.116095+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000066","title":"Variability in immune response genes and prediction of severe SARS-CoV-2 infection (INMUNGEN-Cov2 project)","description":"Genetic factors may contribute to explain the variable clinical response to SARS-CoV-2 infection. To this end we sequenced the DNA of 392 COVID-19 patients from Spain. Whole Exome Sequencing (WES) was performed at two different sequencing centers. Half of the samples were sequenced at a commercial service, NIMGenetics, whereas the other half were sequenced by the EASI-Genomics consortium. \r\nFinally, Variant Call Format (VCF) files for each sample was also obtained.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-24T15:35:03.922545+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000067","title":"Genomic determinants of response and resistance to inotuzumab in B-ALL","description":"Inotuzumab Ozogamicin (InO) is an antibody-drug conjugate which delivers calicheamicin to CD22-expressing cells. In a retrospective cohort of InO treated B-cell acute lymphoblastic leukemia (B-ALL) patients, we sought to understand the genomic determinants of response to InO. Acquired CD22 mutations were observed in 11% (3/27) of post-InO relapsed samples. CD22 mutation types were diverse (frameshift, nonsense, missense and stoploss) and we identified multiple mechanisms of mutation induced CD22 escape, including protein truncation, protein destabilization, and epitope alteration. Accelerated acquisition of mutations by error-prone DNA damage repair could drive CD22 mutation and escape. Acquired loss-of-function mutations in TP53, ATM and CDKN2A were observed, suggesting compromise of the G1/S DNA damage checkpoint as a mechanism of evading InO-induced apoptosis. In conclusion, genetic alterations modulating CD22 expression and DNA damage response influence InO efficacy. The diverse mechanisms of CD22 escape advocates for a refined approach for monitoring CD22-targeted therapy. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-20T15:30:23.168914+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000068","title":"Single-Cell RNA-seq of Primary High Grade Serous Carcinoma","description":"Single-cell RNA Sequencing of CD45- cancer cells. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-05T14:50:27.786486+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000069","title":"Whole genome bisulfite sequencing of prostate cancer samples upon oral pimonidazole administration","description":"Whole genome bisulfite sequencing was performed using laser-capture of microdissected specimen sections comparing PIMO positive and negative carcinoma areas. A hypoxia related methylation molecular signature was generated.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-12-15T09:53:23.515915+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000070","title":"A proteogenomic atlas of the human neural retina","description":"The human neural retina is enriched for alternative splicing, and it is estimated that more than 10% of variants associated with inherited retinal diseases (IRDs) alter splicing. Previous research mainly used short-read RNA-sequencing techniques to investigate retina-specific splicing and splicing factors. However, this technique provides limited information about transcript isoforms. To gain a deeper understanding of the human neural retina and its isoforms, we generated a proteogenomic atlas that combines PacBio long-read RNA-sequencing data with mass-spectrometry and whole-genome sequencing data from three healthy human neural retina samples. About one third of the nearly 60,000 transcript isoforms were novel, and ten novel peptides that confirmed novel isoforms were detected. This study highlights the importance of studying tissue-specific transcriptomes in greater detail to better understand tissue-specific regulation and to identify disease-causing variants.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-02T11:01:33.612045+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000071","title":"Identification of intronic sequences promoting natural skipping of ABCA4 exon 15 using long-read transcriptomics and midigene assays","description":"Stargardt disease is an inherited retinal disease that leads to progressive loss of vision, and is caused by biallelic variants in the ABCA4 gene. A significant proportion of ABCA4 variants of variable penetrance affect pre-mRNA splicing. Previously, we observed the exclusion of certain ABCA4 exons into the final transcript in the absence of any disease-causing variants. In this study, we explored this phenomenon that we coined natural exon skipping (NES) for the entire ABCA4 transcript, using targeted RT-PCR analysis as well as long-read transcriptome sequencing of control retina samples. For the most abundant NES event, which is skipping of ABCA4 exon 15, overlapping ABCA4 deletion constructs were employed to identify responsible cis-regulatory sequence motifs.  Subsequently, antisense oligonucleotides (AONs) were designed and tested to reverse NES and restore fully-spliced ABCA4 mRNA. We identified intronic regions on each side of exon 15 that, when deleted, increased the inclusion of exon 15 in the final transcripts. Interestingly, these motifs appear to work in a synergistic manner. Further fine-mapping of these regions revealed several cis-regulatory motifs that may be responsible for inducing NES, on each side of the exon. AONs targeting these motifs unfortunately did not decrease the skipping of exon 15. In conclusion, we discovered an intriguing phenomenon that, in the absence of disease-causing variants, results in the skipping of one or more exons in the ABCA4 transcript. These NES events appear to be regulated by cis-regulatory motifs within the flanking introns. This work captured the extend of NES throughout ABCA4 transcript and the role of cis-regulatory motifs in pre-mRNA splicing.. The use of AONs targeting cis-regulatory motifs is an innovative strategy for splicing modulation, suitable for complementing future variant-specific splicing modulation therapies in ABCA4 retinopathies.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-12-11T15:56:43.032148+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000072","title":"Genomic Profiling of Pediatric Tumors by Cell Free DNA Sequencing","description":"BACKGROUND\r\nAnalysis of cell-free DNA (cfDNA) from peripheral blood has been studied extensively for detection and monitoring therapy response in adult cancers, but utility in pediatric tumors is unclear.\r\nMETHODS\r\nWe studied 233 children with hematologic, solid and brain tumors. cfDNA was extracted from 1 mL of plasma collected at diagnosis. Circulating tumor DNA (ctDNA) in cfDNA was quantified and diverse classes of somatic genomic variants were detected using PeCan-Seq.  PeCan-Seq findings were compared with matched tumor whole-genome and whole-exome sequencing data. Minimal residual disease (MRD) status was evaluated by cfDNA PeCan-Seq in 14 patients with B-cell acute lymphoblastic leukemia.\r\nRESULTS\r\nPlasma cfDNA yields at diagnosis were higher for hematologic malignancies than for solid and brain tumors. Patients with hematologic malignancy were 100% ctDNA-positive, the median ctDNA fraction in cfDNA was 0.77. We detected 97% variants that were present in tumors and covered by the capture panel, and 50 subclonal variants that were present in cfDNA only. Our approach enabled detection of sequence and structural variants in B-ALL ctDNA at varying levels of MRD. Nineteen of 38 patients with solid tumors were ctDNA-positive, with high prevalence in Ewing Sarcoma, liver tumors and osteosarcoma. One of 19 brain tumor patients was ct-DNA positive, indicating lack of utility for plasma-derived cfDNA in this disease. Notably, cfDNA analysis of a single plasma sample identified genomic features in ctDNA derived from B-ALL, concurrent primary neuroblastoma, and a later neuroblastoma relapse, indicating that genomic variations from multiple tumors could be detected simultaneously.\r\nCONCLUSIONS\r\nPediatric patients with hematologic malignancy had an abundance of plasma ctDNA at diagnosis. Plasma ctDNA levels varied between different solid tumor types, more studies are needed to determine utility. Panel-based cfDNA sequencing could serve as a non-invasive approach for pediatric cancer diagnosis and disease monitoring.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-29T14:07:06.854241+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000073","title":"Comparison of the single-cell and single-nucleus hepatic myeloid landscape within decompensated cirrhosis patients","description":"In-patient comparison of single-cell RNA-sequencing (scRNA-seq) and single-nucleus (snRNA-seq) technologies and accompanying tissue processing protocols on transjugular liver biopsy from decompensated cirrhosis patients (n = 3). ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-27T15:54:40.190654+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000074","title":"Enhancing OSCC Prediction: The Prognostic Power of WPOI and Tumor Budding, and the Limited Impact of Molecular Resection Margins","description":"This dataset contains sequences with results of mutations observed in patients with oral squamous cell carcinoma. Mutations were detected by NGS in tumor tissue, tumor margins, and peripheral blood as a healthy control. Study was using a panel of 88 cancer-related genes, which were selected based on a literature search.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000075","title":"Targeted sequencing (paired) of HR genes in primary and metastatic patient-derived xenografts (PDXs) of colorectal cancer (CRC)","description":"Chemotherapy is the standard-of-care treatment for metastatic colorectal cancer (mCRC) and benefits some patients, but what distinguishes responders from non-responders is unclear. In this study, we leveraged a comprehensive collection of 69 molecularly annotated patient-derived xenografts to uncover functional predictors of response to 5-FU and irinotecan combination therapy (FOLFIRI) in mCRC. Genetic analyses revealed that treatment sensitivity was marked by genomic scars indicative of BRCAness, suggesting homologous recombination (HR) deficiency as a key determinant. Accordingly, we surveyed a manually curated panel of 44 genes with a documented role in HR for the potential presence of pathogenic mutations. We did not observe a specific enrichment of HR gene mutations based on response to FOLFIRI. This result, combined with the absence of widespread biallelic inactivation of the analyzed genes and the predominance of mutations categorized as variants of unknown significance, suggests that FOLFIRI sensitivity is not primarily governed by underlying mutations in HR genes responsible for mitigating the genotoxic effects of this therapeutic regimen.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-12-01T10:05:35.445881+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000076","title":"ATAC-seq in KMS11 vs TKO cells","description":"ATAC-seq to determine chromatin accessibility in t(4;14) Myeloma cell line KMS11 and KMS11 cells with knock-out of the translocated NSD2 allele. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000077","title":"ChIP-seq in KMS11 and TKO cells","description":"Histone chIP-seq in t(4;14) Myeloma cell line KMS11 and KMS11 cells with knock-out of translocated NSD2 allele (KMS11 TKO). ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000078","title":"MicroC in KMS11 and TKO cells","description":"MicroC to show high resolution chromatin interactions in t(4;14) Myeloma cell line KMS11 and KMS11 cells with knock-out of translocated NSD2 allele (KMS11 TKO).","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000079","title":"Exome sequencing in HIV+ Viremic Non-Progressors (VNPs) and HIV+ Progressors","description":"Viremic Non-Progressors (VNPs) maintain normal CD4+ T-cell counts despite uncontrolled HIV-1 replication, but mechanisms leading to CD4+ T-cell preservation are incompletely characterized. We aim to generate a comprehensive understanding of this infrequent phenotype by comparing rates of cellular infection, immunophenotype, genomics, single-cell transcriptomics, metabolomics, and levels of plasma biomarkers in 16 VNPs and 29 HIV+ Progressors. During chronic infection VNPs show lower frequency of HIV-1-infected cells in periphery, which is associated with reduced CCR5 expression and higher prevalence of CCR5Δ32 heterozygosity. The CD8+ T-cell compartment displays a less cytotoxic and less activated phenotype in VNPs. Moreover, despite similar viremia, we found lower bystander CD4+ T-cell death in the VNPs, together with weaker IFN responses, reduced plasma levels of zonulin (a biomarker of intestinal permeability), altered tryptophan catabolism, and preserved LPS responsiveness in vitro. Overall, a complex multifactorial mechanism, suggesting gut-associated lymphoid tissue preservation, underlies resistance to HIV pathogenesis in VNPs.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-25T13:13:12.310345+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000080","title":"CHEK2 molecular manuscript","description":"This study investigated the molecular landscape of 17 tumors from 9 individuals with biallelic germline pathogenic variants in CHEK2. Tumors included breast and non-breast cancers, and WES and sWGS bam files from the tumors are included in this submission. \r\nWES data was aligned to GRCh37 and sWGS data to GRCh38.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-15T14:36:19.154192+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000081","title":"Tumor mutational landscape in individuals with CMMRD ","description":"Whole exome sequencing data from the tumors (n=16) of individuals with constitutional mismatch repair deficiency.\r\nData was aligned to GRCh38. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-15T14:36:43.817015+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000082","title":"Correlative Genomic Analysis of Durvalumab plus Pazopanib Combination in Patients with Advanced Soft Tissue Sarcomas","description":"We conducted an open-label, phase 2 study to determine the activity of the anti-VEGF receptor tyrosine-kinase inhibitor, pazopanib, combined with the anti-PD-L1 immune checkpoint inhibitor, durvalumab, in unselected advanced sarcomas. In addition, we conducted whole exome and transcriptomic sequencing with pre-treatment tissue biopsy to correlate clinical outcomes with molecular and genomic biomarkers to identify patients who would most likely benefit from the combination treatment.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-05T12:20:39.829846+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000083","title":"Effects of interferon-gamma treatment on human small intestinal organoids generated from healthy donors","description":"The intestine is vulnerable to interferon-gamma as intestinal epithelial stem cells undergo cell death when exposed to interferon-gamma. Here, we developed a novel human intestinal organoid-based 3D model system to study the effects of interferon-gamma-induced intestinal epithelial damage at the RNA level. We treated organoids with 10 ng/mL for either 6 or 18h. Knowledge generated with this dataset is relevant for a variaty of intestinal pathologies with an immune component, for instance graft-versus-host disease.\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-12-20T13:13:26.864273+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000084","title":"PDX gene expression","description":"Investigation of the anti-tumor activity of the potent, highly selective, orally bioavailable CHK1 inhibitor (CHK1i), SRA737, in both acquired PARPi-resistant BRCA1/2 mutant and CCNE1amp high-grade serous ovarian cancer (HGSOC) models. We analyzed gene expression in five patient derived xenografts (PDX) that responded to CHK1i and three PDX that had a poor response to CHK1i.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-12T11:35:35.291111+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000085","title":"Genome-wide methylation profiling by high-throughput sequencing of tissue (resident) versus blood circulating memory T lymphocyte populations","description":"This study contains RRBS data generated from 54 ex vivo samples, including CD4+ Trm (2x intestine, 2x lung, and 3x skin), CD4+CD69- tissue cells (2x bone marrow, 2x spleen, 2x intestine, 2x lung, and 3x skin), CD8+ Trm (2x bone marrow, 2x spleen, 2x intestine, 2x lung, and 3x skin),  CD8+CD69- tissue cells (2x bone marrow, 2x spleen, 2x intestine, 2x lung, and 2x skin), blood CD4+ (7x) and CD8+ (8x) memory T cells.  ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000086","title":"Synthetic - FEGA Sweden Heilsa synthetic dataset December 2023","description":"Synthetic - This submission contains a subset of a synthetic dataset derived from the project Heilsa Tryggvedottir - a Nordic collaboration on sharing sensitive human data. Heilsa Tryggvedottir is funded by the Nordic e-Infrastructure Collaboration (NeIC), the ELIXIR nodes of Finland, Norway, and Sweden, Computerome in Denmark, and the Estonian Scientific Computing Infrastructure (ETAIS).\r\n\r\nIn the synthetic data creation process, it was attempted to strike a fine balance between the usability of the datasets (e.g. technical FEGA development, testing, user training, and basic bioinformatics) and compliance with GDPR. File names and file content (e.g. headers in fastq) are anonymized. Moreover, the X, Y, and mitochondrial sequences have been discarded from the original data since these data can be used for maternal, paternal, or ethnic origin tracing. The dataset does not follow natural haplotype distribution (inherent to imputation panels). The only inputs derived from real sequence data are variant distribution density per chromosome and learning sequencing error models.\r\n\r\nThe synthetic dataset consists of two fastq files, a cram file, a vcf file, and two index files. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-12-11T14:07:17.501776+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000087","title":"RNA-Sequencing of cervical cancers","description":"Question: Can we identify cervical cancer patients who are at risk for distant metastatic (DM) recurrence following treatment with radiotherapy, concurrent weekly cisplatin and brachytherapy (RTCT). \r\nFindings: An immune-based 55 gene risk score was developed using a cohort of 81 patients treated with RTCT that was strongly predictive of DM and cause-specific survival (CSS). The risk score was validated in two independent patient cohorts. A high immune metastatic risk score was associated with a high tumor mutational burden and a ‘cold’, immune-excluded tumor microenvironment at diagnosis.\r\nMeaning: The immune gene expression risk score may help to identify patients at risk of DM and potential targets for mitigating this risk. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-31T14:42:14.579849+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000090","title":"300BCG study: human population variation of trained immunity","description":"To investigate human population variation of trained immunity, we immunized healthy individuals with Bacillus Calmette-Guérin (BCG). This live attenuated vaccine induces not only an adaptive immune response against tuberculosis, but also triggers innate immune activation and memory. We established personal chromatin accessibility maps over a time course of BCG vaccination in the 300BCG cohort using ATAC-seq.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-09T12:50:07.575835+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000091","title":"The Genomic Map of Poland in Open Access","description":"The main goal is to prepare and share WGS/WES of Polish population\r\nIn this project NGS (next generation sequencing) was performed using Illumina NOVASEQ 6000 and Illumina DRAGEN aligner was used.\r\nShared BAM and BAM.BAI files\r\nLibrary Construction Protocol: Illumina DNA PCR-Free Prep, Tagmentation.\r\nReference Genome: GRCh37.\r\n","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-12-15T13:46:22.74246+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000092","title":"The Genomic Map of Poland in Open Access","description":"The main goal is to prepare and share WGS/WES of Polish population","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000093","title":"The Genomic Map of Polad in Open Access","description":"The main goal is to prepare and share WGS/WES of Polish population","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000094","title":"The Genomic Map of Polad in Open Access","description":"Part of the population based Cohort of Polish inviduals POPULOUS (bbmri-eric:ID:PL_BLUL:collection:POPULOUS_BLUL)","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000095","title":"The Genomic Map of Polad in Open Access","description":"The main goal is to prepare and share WGS/WES of Polish population","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000096","title":"The Genomic Map of Poland in Open Access","description":"The main goal is to prepare and share WGS/WES of Polish population\r\nIn this project NGS (next generation sequencing) was performed using Illumina NOVASEQ 6000 and Illumina DRAGEN aligner was used.\r\nShared BAM and BAM.BAI files\r\nLibrary Construction Protocol: Illumina DNA PCR-Free Prep, Tagmentation.\r\nReference Genome: GRCh37.\r\n","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2023-12-21T15:58:25.129338+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000097","title":"scRNA-seq of monochorionic dizygotic twin chimera PBMC","description":"Single cell RNA-seq of PBMC of monochorionic dizygotic twin chimeras. 10x chromium v3.1 was used to generate barcoded scRNA library.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-05T16:33:30.741841+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000098","title":"LCM-isolated buccal epithelial cell sequencing","description":"Single buccal epithelial cells were dissected and collected on an adhesive cap  with laser capture microdissection (LCM) with approximately 13-60 cells per cap. Each adhesive cap containing 13-60 cells was independently processed with QIAamp DNA micro kit (Qiagen) for DNA extraction. The NEBNext ultra II FS DNA library kit was used to prepare DNA libraries with low starting material. Paired-end whole genome sequencing reads were obtained with the NovaSeq. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-05T16:33:28.926735+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000099","title":"Community efforts can form the ground to unravel complex biology of the human neuronal landscape to understand neurodegeneration","description":"Precise determination of cellular identity and molecular phenotypes through advanced high-throughput technologies is crucial for understanding intricate tissue functions, especially in complex organs like the brain. This becomes pivotal for a comprehensive mapping of cell identities throughout the human brain to unravel its function. In this study, we present findings from a multi-center investigation involving seven genome centers. We analyzed single-nucleus transcriptomes obtained from NeuN+ neurons from the putamen and caudate nucleus of both healthy individuals and Parkinson's Disease (PD) patients. Our results demonstrate the potential for establishing community-wide standards, fostering collaborative networks, and enhancing brain cell classification efforts. We propose a transcriptional architecture that encodes synaptic communication patterns in the striatum, comprising of cell-adhesion molecules (CAMs), transmitter/modulator receptors, ion channels, signaling proteins, neuropeptides, vesicular release components, and transcription factors. This classification serves as a foundation for finely mapping and integrating publicly available datasets, showcasing the value of deep sampling in defined brain regions for comprehensive brain-wide analyses. Importantly, this nomenclature can serve as a template for other brain regions. Crucially, our proposed molecular phenotypes enable the precise mapping of cellular alterations in Parkinson's Disease. Transcriptional changes predominantly occur in specific cell states of medium spiny neurons within the putamen matrix, leading to increased excitability. Additionally, a disbalance in specific interneuron cell states is associated with heightened glutamatergic signaling, further contributing to increased overall excitability.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000100","title":"Paired primary and recurrent patient GBM sample EZH2 binding profiles","description":"To ascertain the change in PRC2 occupancy at different promoter sets between primary and recurrent tumour, we performed EZH2 ChIPseq in longitudinal GBM samples from one Up and one Down responder from our cohort.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-22T11:49:45.679087+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000101","title":"WNT-dependent interaction between inflammatory fibroblasts and FOLR2+ macrophages promotes fibrosis in chronic kidney disease","description":"Chronic kidney disease (CKD) is a public health problem driven by myofibroblast accumulation, leading to interstitial fibrosis. Heterogeneity is a recently recognised characteristics in kidney fibroblasts in CKD, but the role of different populations is still unclear. Here, we characterize a proinflammatory fibroblast population (named CXCL-iFibro), which corresponds to an early state of myofibroblast differentiation in CKD. By performing immunofluorescence studies and spatial transcriptomics analysis on 2 patients, we demonstrate that CXCL-iFibro co-localize with macrophages in the kidney and participate in their attraction, accumulation, and switch into FOLR2+ macrophages from early CKD stages on. In vitro, we cultured primary inflammatory fibroblasts that we characterized by using bulk RNAseq. We show that macrophages promote the switch of CXCL-iFibro into ECM-secreting myofibroblasts through a WNT/-catenin-dependent pathway, thereby suggesting a reciprocal crosstalk between these populations of fibroblasts and macrophages. Finally, the detection of CXCL-iFibro at early stages of CKD is predictive of poor patient prognosis, which shows that the CXCL-iFibro population is an early player in CKD progression and demonstrates the clinical relevance of our findings.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-03T10:16:54.990471+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000102","title":"Tumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patient","description":"Single cell RNA and TCR sequencing of gamma delta T cells from two Merkel cell carcinoma patients","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-03T09:45:02.650798+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000103","title":"AVENIO Expanded ctDNA panel sequence alignments (BAMs) from plasma DNA of lung cancer patients from the OSCILLATE trial ","description":"The AVENIO ctDNA Expanded Kit is a next-generation sequencing (NGS) liquid biopsy assay with a 77 gene panel (192 kb) containing genes in U.S. National Comprehensive Cancer Network (NCCN) Guidelines and emerging cancer biomarkers. This pan-cancer assay was applied to 100 plasma samples from patients with lung cancer undergoing treatment in the OSCILLATE trial. After 150 bp paired-end sequencing, reads were aligned to the human genome reference with the AVENIO Oncology Analysis Software. These files are the sorted non-deduplicated alignments generated by the analysis software used for subsequent variant, indel and CNV calling.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-03T18:45:26.625763+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000104","title":"Immunomodulatory effects and improved outcomes with cisplatin- vs carboplatin-based chemotherapy plus atezolizumab in urothelial cancer","description":"In metastatic urothelial cancer (mUC), cisplatin versus carboplatin leads to durable disease control in a subset of patients. The IMvigor130 trial reveals more favorable effects with atezolizumab combined with gemcitabine and cisplatin (GemCis) versus gemcitabine and carboplatin (GemCarbo). This study investigates the immunomodulatory effects of cisplatin as a potential explanation for these observations. Our findings indicate that improved outcomes with GemCis versus GemCarbo are primarily observed in patients with pretreatment tumors exhibiting features of restrained adaptive immunity. Additionally, GemCis versus GemCarbo ± atezolizumab induces transcriptional changes in circulating immune cells, including upregulation of antigen presentation and T-cell activation programs. In vitro experiments demonstrate that cisplatin, compared with carboplatin, exerts direct immunomodulatory effects on cancer cells, promoting dendritic cell activation and antigen-specific T cell killing. These results underscore the key role of immune modulation in cisplatin's efficacy in mUC and highlight the importance of specific chemotherapy backbones in immunotherapy combination regimens.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-02T10:56:41.137022+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000105","title":"Efficacy and safety of entrectinib in patients with ROS1-positive advanced/metastatic non-small cell lung cancer (NSCLC) from the Blood First Assay Screening Trial (BFAST)","description":"BFAST is a global, open-label, multicohort trial that evaluates the efficacy and safety of multiple therapies in patients with advanced/metastatic NSCLC and targetable alterations, identified by blood-based molecular testing. We present data from Cohort D (ROS1-positive). Patients ≥18 years old with stage IIIB/IV, ROS1-positive NSCLC detected by blood-based testing, received entrectinib 600 mg daily. At data cut-off (November 2021), 55 patients were enrolled and 54 had measurable disease. Cohort D met its primary endpoint; the confirmed objective response rate (ORR) by investigator was 81.5% which was consistent with the ORR from the integrated analysis of entrectinib (investigator-assessed ORR: 73.4%, data cut-off May 2019, ≥12 months follow-up). The safety profile of entrectinib was consistent with prior reports. These results demonstrate consistency with those from the integrated analysis of entrectinib in patients with ROS1-positive NSCLC identified by tissue-based testing and support the clinical value of blood-based testing to inform clinical decision-making.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-21T13:14:48.054476+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000106","title":"Heterogeneity of IKZF1 genomic alterations and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia","description":"Purpose \r\nGenomic alterations of IKZF1 are common and associated with adverse clinical features in B-ALL, but the relationship between the type of IKZF1 alteration, disease subtype and outcome are incompletely understood.  \r\nPatients and Methods  \r\nWe used transcriptome and genomic sequencing, and SNP microarray data to determine leukemia subtype and genomic alterations for 688 pediatric patients with B-ALL enrolled into St. Jude Total Therapy 15 and 16 studies. \r\nResults  \r\nIKZF1 alterations were identified in 115 (16.7%) patients, commonly in BCR::ABL1 (78%) and CRLF2-rearranged, BCR::ABL1-like B-ALL (70%), and were associated with five-year cumulative incidence of relapse (CIR) of 14.8 ± 3.3% compared to 5.0 ± 0.9% for patients without any IKZF1 alteration (P < 0.0001). IKZF1 deletions of exon 4-7 (P = 0.0002), genomic IKZF1plus with any IKZF1 deletion (P = 0.006) or with focal IKZF1 deletion (P = 0.0007), and unfavorable genomic subtypes (P < 0.005) were independently adversely prognostic. Patients with both IKZF1 exon 4-7 deletion and unfavorable genomic subtype had a significantly increased risk of relapse (HR = 58.3; 95% CI, 11.9 – 285.4, P < 0.0001) whereas IKZF1 sequence mutations were not independently predictive of outcome. \r\nConclusions \r\nGenomic IKZF1plus with any IKZF1 deletion, IKZF1 deletion of exon 4-7, and unfavorable subtype confer increased risk of relapse. The combination of unfavorable genomic subtype and IKZF1 deletion of exon 4-7 identified patients at greatest risk of relapse despite MRD-directed therapy. The type of IKZF1 alteration together with subtype are informative for risk stratification and predict response in patients with B-ALL. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-30T12:59:42.794393+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000107","title":"Clones derived from early passage tumoroids of colorectal cancer","description":"We obtained different clones from early passage CRC tumoroids to study mutational signatures specific for truncal or private somatic alterations. These whole genome sequences are part of a larger study on the heterogeneity and evolution of DNA mutation rates in microsatellite-stable colorectal cancer.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-05T15:14:18.916995+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000108","title":"Transcriptomic profiles of early and late passage metastatic colorectal cancer (mCRC) tumoroids","description":"The breadth and depth at which cancer models are interrogated contribute to successful translation of drug discovery efforts to the clinic. In colorectal cancer (CRC), model availability is limited by a dearth of large-scale collections of patient-derived xenografts (PDXs) and paired tumoroids from metastatic disease, the setting where experimental therapies are typically tested. XENTURION is a unique open-science resource that combines a platform of 129 PDX models and a sister platform of 129 matched PDX-derived tumoroids (PDXTs) from patients with metastatic CRC, with accompanying multidimensional molecular and therapeutic characterization. This specific dataset is focused on a comparison of early and late passage tumoroids transcriptomes.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-05T17:24:00.639119+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000109","title":"Effect of ETS2 modulation on chromatin accessibility and enhancer activity in inflammatory (TPP) macrophages","description":"This dataset consists of H3K27ac ChIP-seq and ATAC-seq in primary human macrophages following modulation of ETS2 expression. There are three datasets: H3K27ac ChIP-seq in ETS2-edited and unedited inflammatory (TPP) macrophages, H3K27ac ChIP-seq in ETS2-overexpressing and control M0 macrophages, and ATAC-seq in ETS2-edited and unedited inflammatory macrophages. For editing experiments, monocytes were transfected with CRISPR-Cas9 ribonucleoproteins containing a gRNA that was validated to edit ETS2, or a non-targeting control gRNA. Inflammatory macrophage differentiation was performed using conditions that model chronic inflammation (TPP): 3 days GM-CSF (50ng/mL) followed by 3 days GM-CSF, TNFa (50ng/mL), PGE2 (1mg/mL), and Pam3CSK4 (1mg/mL). For overexpression experiments, controlled overexpression of ETS2 mRNA or control mRNA (an equivalent amount of mRNA encoding the reverse complement of ETS2 – thereby controlling for the quantity, length and purine/pyrimidine composition of the transfected RNA but with a transcript that would not be translated) was induced in resting, non-activated (M0) macrophages by transfecting 500ng mRNA. To minimise non-specific activation due to the transfected RNA, in vitro transcription was performed using co-transcriptional capping (to minimise uncapped products), and incorporating modified, minimally immunogenic nucleotides (replacing uridine with N1-methyl-pseudouridine and cytidine with methylcytidine). After 18 hours, transfected cells were were activated with low dose LPS and harvested 6 hours later. \r\n\r\nFor H3K27ac ChIP-seq, cells were harvested, cross-linked, quenched, lysed, and sheared. Immunoprecipitation of histone-DNA complexes was performed overnight at 4C with rotation using an anti-H3K27ac antibody and the SimpleChIP Plus Sonication ChIP kit (Cell Signaling Technology). Following reverse cross-linking, 50ng of immunoprecipitated DNA or input DNA were used to prepare sequencing libraries using the iDeal Library Preparation kit (Diagenode), according to manufacturer instructions. 10 PCR cycles were used for the amplification step and size selection was not performed. The quality and molarity of all libraries was assessed using a BioAnalyzer 2100 (Agilent) and the libraries were sequenced on an Illumina NovaSeq 6000. Raw data are provided as raw and aligned sequencing reads from H3K27ac-bound DNA and the input chromatin. \r\n\r\nATAC-seq in TPP macrophages was performed using the Omni-ATAC protocol (Corces et al 2017) with the following modifications: cell number was increased to 75,000 cells, cell lysis time was increased to 5 minutes; volume of Tn5 transposase in the transposition mixture was doubled; duration of the transposition step was extended to 40 minutes. Sequencing libraries were prepared by PCR with the NEBNext Ultra II Q5Master Mix (NEB) as described previously (Corces et al 2017). Amplified libraries were cleaned using AMPure XP beads (Beckman Coulter). Sequencing reads were trimmed using TrimGalore! (Phred score 24), filtered to remove reads < 20 bp and aligned to the human genome (hg19) using Burrows-Wheeler Aligner (BWA). Aligned reads were converted to BAM files, sorted and indexed using SAMtools (Li et al, 2009). PCR duplicates and unmapped reads were removed, and the resulting BAM files were re-sorted and indexed. Raw data are provided as 100 bp paired-end Illumina reads from n = 3 donors for each experiment. BAM files are also provided. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-31T14:50:08.98547+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000110","title":"The Genomic Map of Polad in Open Access","description":"The main goal is to prepare and share WGS/WES of Polish population","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000111","title":"The Genomic Map of Polad in Open Access","description":"The main goal is to prepare and share WGS/WES of Polish population","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000112","title":"The Genomic Map of Polad in Open Access","description":"The main goal is to prepare and share WGS/WES of Polish population","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000113","title":"The Genomic Map of Polad in Open Access","description":"The main goal is to prepare and share WGS/WES of Polish population","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000114","title":"Whole genome sequencing to detect spontaneous acquired mutations in mismatch repair-deficient human colon organoids","description":"Individual outgrowing organoids surviving the medium-based selection were manually picked and propagated as clonal lines for a couple of passages to avoid unexpected mutation accumulation before being harvested for WGS/WES. 1 µg of DNA was used for WGS/WES by Agilent SureSelect V7 kit, with 8Gb per sample (50X average mapped) data throughput, sequencing on NovaSeq 150PE\r\n","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-06T15:59:00.560197+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000115","title":"The Genomic Map of Polad in Open Access","description":"The main goal is to prepare and share WGS/WES of Polish population","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000116","title":"The Genomic Map of Polad in Open Access","description":"The main goal is to prepare and share WGS/WES of Polish population","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000117","title":"The Genomic Map of Polad in Open Access","description":"The main goal is to prepare and share WGS/WES of Polish population","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000118","title":"The Genomic Map of Polad in Open Access","description":"The main goal is to prepare and share WGS/WES of Polish population","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000119","title":"The Genomic Map of Polad in Open Access","description":"The main goal is to prepare and share WGS/WES of Polish population","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000120","title":"The Genomic Map of Polad in Open Access","description":"The main goal is to prepare and share WGS/WES of Polish population","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000121","title":"The Genomic Map of Polad in Open Access","description":"The main goal is to prepare and share WGS/WES of Polish population","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000122","title":"ctDNA Quantification in Blood Plasma Using Deep Learning Based Fragle Tool","description":"The project aims to develop an easy to use software named Fragle that can quantify ctDNA in blood plasma. This can help in cancer screening and progress monitoring from simple blood test without any need for tumor biopsy. We aim to make Fragle usable for both low pass whole genome sequencing and targeted sequencing data of cell free DNA. Fragle can work directly on the raw bam files mapped to hg19/GRCh37. We are uploading the bam files used in this study for Fragle evaluation.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-05T09:18:44.416145+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000123","title":"Arcagen – thoracic malignancies","description":"Arcagen is an EORTC/SPECTA pan-European project that aims to recruit 1000 rare cancer patients from different tumour domains of EURACAN. This study collected samples from advanced or metastatic rare cancer from patients older than 12, and analysed them using Foundation Medicine next-generation sequencing (NGS) panels (FoundationOne CDx for FFPE samples or FoundationOne Liquid CDx for blood samples). Here we are submitting the dataset that contain NGS files from rare thoracic malignancies (n=102)","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-08T17:24:02.838107+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000124","title":"Prognostic whole-genome and transcriptome signatures in colorectal cancers","description":"Colorectal cancer (CRC) is caused by a sequence of somatic genomic alterations affecting driver genes in core cancer pathways1. To understand the functional and prognostic impact of cancer-causing somatic mutations, we analysed the whole genomes and transcriptomes of 1,063 primary CRCs in a population-based cohort with long-term follow-up. This study constitutes the largest integrated genome and transcriptome analysis of CRC to date, and links mutations, gene expressions and patient outcomes.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[39112715],"external_links":null,"is_released":true,"released_date":"2024-05-15T16:58:02.82233+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000125","title":"\tSingle cell RNA sequencing on failed heart from HF patients","description":"To explore the transcriptome profile of cells in heart failure patients, we isolated single cells from patient’ heart undergoing heart transplantation. The 3’ expression library was generated with Chromium Single Cell 3’ Library, Gel Dead & multiplex kit and Chip Kit (v3, 10x Genomics). After sequencing with Illumina Hiseq4000 and data analysis, we identified the major cell composition in heart failure and the sub-cell types specific in different types of heart disease.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-30T08:29:33.801155+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000126","title":"WES data from tumors and matching controls collected from 11 UTSW translocation renal cell carcinoma (tRCC) patients.","description":"This study investigates the progression of translocation renal cell carcinoma (tRCC) based on Whole Exome Sequencing (WES) data from 11 patients. The samples were collected from affiliated hospitals of the University of Texas Southwestern Medical Center (UTSW), including Parkland Hospital and Children’s Medical Center. Tumor samples and their matched normal DNA were sequenced on the Illumina platform.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-18T09:52:51.034427+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000127","title":"RNA-Seq data from tumor samples collected from 12 UTSW translocation renal cell carcinoma (tRCC) patients.","description":"This study investigates differentially expressed genes associated with the progression of translocation renal cell carcinoma (tRCC) by analyzing RNA-Seq data from 23 tumor samples obtained from 12 patients. The samples were collected from affiliated hospitals of the University of Texas Southwestern Medical Center (UTSW), including Parkland Hospital and Children’s Medical Center. RNA isolated from tumor samples was sequenced using the Illumina platform.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-18T09:52:52.716031+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000128","title":"Pharmacological improvement of CFTR function rescues airway epithelial homeostasis and host defense in cystic fibrosis children","description":"Rationale: Recent clinical trials have shown that elexacaftor/tezacaftor/ivacaftor (ETI) provides significant benefit to patients with cystic fibrosis (CF) by improving CFTR function. Despite these promising clinical findings, the specific effects on the airway inflammatory status leading to structural damage and impaired lung function, remain elusive. \r\n\r\nObjectives: We investigated the transcriptional changes at the single cell level of airway epithelial and immune cells that underlie the clinical improvement by ETI therapy in children with CF. \r\n\r\nMethods: Nasal swabs from thirteen children with CF and at least one F508del allele  aged 6 to 12 years were collected at baseline and three months after initiation of ETI and subjected to scRNA-seq. In addition, we collected nasal swabs from 12 age- and sex-matched controls. Sweat chloride concentrations, spirometry and multiple breath washout were used for clinical evaluation of CF children. \r\n\r\nMeasurements and main results: ETI significantly reduced sweat chloride concentrations (-52.2 ± 14.3 mmol/L, P < 0.001) and improved the lung clearance index (-1.3 ± 1.8, P < 0.05). Single cell transcriptomics revealed an impaired interferon signalling in epithelial cells of CF children at baseline, which was partially restored by ETI in conjunction with an ETI-induced increase in expression of MHC I and II encoding genes similar to control levels. Additionally, ETI markedly reduced the inflammatory phenotype of immune cells, particularly of neutrophils and macrophages. \r\n\r\nConclusions: Improvement of CFTR function by ETI restores epithelial homeostasis and reduces immune cell inflammatory responses in the upper airways of children with CF, highlighting the potential of early initiation of ETI therapy.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-26T17:26:08.777985+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000129","title":"Non-coding mutations drive persistence of a founder pre-leukemic clone which initiates late relapse in T-ALL","description":"T-ALL relapse usually occurs early but can occur much later, which has been suggested to represent a de novo leukemia. However, we conclusively demonstrate late relapse can evolve from a pre-leukemic subclone harbouring a non-coding mutation that evades initial chemotherapy.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[38194681],"external_links":null,"is_released":true,"released_date":"2024-05-07T13:23:03.222529+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000130","title":"Altered enhancer-promoter interaction leads to MNX1 expression in pediatric acute myeloid leukemia with t(7;12)(q36;p13)","description":"Acute myeloid leukemia (AML) with the t(7;12)(q36;p13) translocation occurs only in very young children and has a poor clinical outcome. The expected oncofusion between breakpoint partners (MNX1 and ETV6) has only been reported in a subset of cases. However, a universal feature is the strong transcript and protein expression of MNX1, a homeobox transcription factor that is normally not expressed in hematopoietic cells. Here, we map the translocation breakpoints on chromosomes 7 and 12 in affected patients to a region proximal to MNX1 and either introns 1 or 2 of ETV6. The frequency of MNX1 overexpression in pediatric AML (n=1556, own and published data) is 2.4% and occurs predominantly in t(7;12)(q36;p13) AML. Chromatin interaction assays in a t(7;12)(q36;p13) iPSC cell line model unravel an enhancer-hijacking event that explains MNX1 overexpression in hematopoietic cells. Our data suggest that enhancer-hijacking is a more common and overlooked mechanism for structural rearrangement-mediated gene activation in AML.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-27T15:28:32.659412+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000131","title":"Low-coverage whole-sequencing of metastasised colorectal cancer samples treated with bevazicumab","description":"Low-coverage whole-genome sequencing (LC-WGS) was performed on tumor tissue, normal tissue and plasma samples collected from mCRC patients from the AC-ANGIOPREDICT Phase II trial (NCT01822444) and the University Medical Center Mannheim (UMM).","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[38811554],"external_links":null,"is_released":true,"released_date":"2024-05-16T12:19:41.722662+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000132","title":"Transcriptomic hallmarks and RNA isoform diversity in human neurodegenerative disease","description":"Single-cell RNA-sequencing (scRNA-seq) has enabled high-throughput RNA analysis at an unprecedented resolution. One staple analysis in scRNA-seq is identifying differentially expressed genes (DEGs) between two populations. However, the mRNA isoforms have often been overlooked in these transcriptomic analyses due to technical limitations. In order to investigate the mRNA isoforms at the single-cell level, we used a targeted single-nucleus long-read RNA-sequencing method combining single-nucleus short-read RNA-seq (snRNA-seq), target gene enrichment, and Iso-Seq. We performed snRNA-seq and targeted single-nucleus Iso-Seq (snIso-Seq) on 25 human frontal cortices from individuals with AD, DLB, or PD, and age-matched controls. Our short-read transcriptome analysis revealed that DLB samples had more overlapping DEGs with AD than PD despite sharing pathological hallmarks with PD. We observed vast RNA isoform diversity in the 50 genes targeted, including genes that were not differentially expressed in our short-read data. We also identified several novel isoforms that are not included in the reference annotation. Our data collectively characterize the transcriptome of various neurodegenerative diseases and illuminate the mRNA isoform diversity.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-20T09:42:36.136679+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000133","title":"Lifelines NEXT","description":"The Lifelines-NEXT is a cohort of newborns followed up from birth up to the age of 1 year and later. The cohort includes approximately 1,500 newborns and their mothers from the 3 provinces of the Northern Netherlands. ","abstract":null,"study_type":"Metagenomics","pubmed_ids":[32100173],"external_links":null,"is_released":true,"released_date":"2024-02-06T16:38:53.697988+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000134","title":"Ascorbic acid modulates the transcriptional landscape of proneural-like Glioblastoma Stem Cells","description":"Glioblastoma (GBM) is a fatal disease with a poor prognosis, whose aetiology involves profound molecular alterations. Given the limited progress made in recent years, research into new therapeutic avenues may improve the treatment of GBM patients. In this work, we have performed a transcriptional profiling of patient-derived Glioblastoma Stem Cells (pd-GBSCs) to study the potential implications of low-dose Ascorbic Acid treatment in regulating the transcriptional rewiring in proneural-like pd-GBSCs.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000135","title":"Cancer-associated fibroblasts promote drug resistance in ALK-driven lung adenocarcinoma cells by upregulating lipid biosynthesis","description":"Targeted therapy interventions using tyrosine kinase inhibitors (TKIs) provide encouraging treatment responses in ALK-rearranged lung adenocarcinomas, yet resistances occur almost inevitably. Apart from tumor cell-intrinsic resistance mechanisms, accumulating evidence supports a role of cancer-associated fibroblasts (CAFs) in affecting the therapeutic vulnerability of lung cancer cells. Here, we aimed to investigate underlying molecular networks shaping the therapeutic susceptibility of ALK-driven lung adenocarcinoma cells via tumor microenvironmental cues using three-dimensional (3D) spheroid co-culture settings. We show that CAFs promote therapy resistance of lung tumor cells against ALK inhibition by reducing apoptotic cell death and increasing cell proliferation. Using single-cell RNA-sequencing analysis, we show that genes involved in lipogenesis constitute the major transcriptional difference between TKI-treated homo- and heterotypic lung tumor spheroids. CAF-conditioned medium and CAF-secreted factors HGF and NRG1 were both able to promote resistance of 3D-cultured ALK-rearranged lung tumor cells via AKT signaling, which was accompanied by enhanced de novo lipogenesis and supression of lipid peroxidation. Notably, simultaneous targeting of ALK and SREBP-1 was able to overcome the established CAF-driven lipid metabolic-supportive niche of TKI-resistant lung tumor spheroids. Our findings highlight a crucial role of CAFs in mediating ALK-TKI resistance via lipid metabolic reprogramming and suggest new ways to overcome resistance towards molecular directed drugs by targeting vulnerabilities downstream of oncogenic signaling.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-23T10:20:11.390419+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000136","title":"Residual ANTXR1+ myofibroblasts after chemotherapy inhibit anti-tumor immunity via YAP1 signaling pathway","description":"Although cancer-associated fibroblast (CAF) heterogeneity is well-established, the impact of chemotherapy on CAF populations remains poorly understood. We address this question in high-grade serous ovarian cancer (HGSOC), in which we previously identified 4 CAF populations. While the global content in stroma increases in HGSOC after chemotherapy, the proportion of FAP+ CAF (also called CAF-S1) decreases. Still, maintenance of high residual CAF-S1 content after chemotherapy is associated with reduced CD8+ T lymphocyte density and poor patient prognosis, emphasizing the importance of CAF-S1 reduction upon treatment. Single cell analysis, spatial transcriptomics and immunohistochemistry reveal that the content in the ECM-producing ANTXR1+ CAF-S1 cluster (ECM-myCAF) is the most affected by chemotherapy. Moreover, functional assays demonstrate that ECM-myCAF isolated from HGSOC reduce CD8+ T-cell cytotoxicity through a Yes Associated Protein 1 (YAP1)-dependent mechanism. Thus, efficient inhibition after treatment of YAP1-signaling pathway in the ECM-myCAF cluster is required to enhance CD8+ T-cell cytotoxicity. Altogether, these data pave the way for novel therapy targeting YAP1 in ECM-myCAF in HGSOC.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-26T17:18:43.861826+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000137","title":"Capmatinib shows superior efficacy for MET-fusion driven pediatric high-grade glioma and synergizes with radiotherapy","description":"Pediatric high-grade glioma (pHGG) is the most frequent malignant brain tumor in children and can be subclassified into multiple entities. Fusion genes activating the MET receptor tyrosine kinase often occur in infant-type hemispheric glioma (IHG) but also in other pHGGs, and are associated with devastating morbidity and mortality. To identify new treatment options, we established and characterized two novel orthotopic mouse models harboring distinct MET fusions. These included an immunocompetent, murine allograft model and patient-derived orthotopic xenografts (PDOX) from a MET-fusion iHG patient who failed conventional therapy and targeted therapy with cabozantinib. With these models, we analyzed the efficacy and pharmacokinetic properties of three MET inhibitors, capmatinib, crizotinib and cabozantinib, alone or combined with radiotherapy (RT).\r\n","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-25T20:36:46.766244+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000138","title":"Immune heterogeneity in small cell lung cancer and vulnerability to immune checkpoint blockade","description":"Following the pivotal Phase III IMpower133 study, atezolizumab (anti–PD-L1), combined with carboplatin and etoposide (CE), was the first immune checkpoint inhibitor approved for first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) and is now a standard of care. A clearer understanding of therapeutically relevant SCLC subsets is needed to improve outcomes and to identify rational combination strategies. Transcriptomic analyses and nonnegative matrix factorization were conducted on 271 pre-treatment patient tumor samples from IMpower133 and four subsets with general concordance to previously reported SCLC subtypes were identified. Deeper investigation into the immune heterogeneity relevant to clinical outcomes uncover two subsets with differing neuroendocrine (NE) versus non-neuroendocrine (non-NE) phenotypes that demonstrated hallmarks of immune cell infiltration. The balance of tumor-associated macrophage (TAM) to T-effector signals distinguished these inflamed subsets. Tumors with low TAM but high T-effector signals had a NE phenotype and demonstrated longer overall survival with PD-L1 blockade and CE versus CE alone than did tumors with high TAM and high T-effector signal, which had a non-NE phenotype. The delineation of SCLC immune heterogeneity offers a clinically relevant approach to discriminate SCLC patients likely to benefit most from immunotherapeutic approaches and highlights the complex mechanisms underlying response and resistance to immune checkpoint blockade. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-26T15:10:19.280738+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000139","title":"Progressive multifocal leukoencephalopathy (PML)","description":"We generated RNAseq, ATACseq, Multiomics and CITEseq for patients with Progressive multifocal leukoencephalopathy (PML) to profile the chromatin accessibility, transcriptional profiles and surface proteins at single-cell level.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-18T10:27:36.337071+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000140","title":"Multi-omic characterisation of PBMCs in IBD","description":"We generated 10X, droplet-based Multiome (paired RNA+ATAC) data of PBMCs in 38 IBD patients. Patients are either UC or CD patients. To test the responsiveness of the cells to bacterial stimuli, we stimulated samples with either RPMI, LPS or S. Salmonella (total: 80 samples).\r\n\r\nSingle-nuclei libraries are multiplexed across donors. Genotypes are provided in this dataset to perform genetic demultiplexing, phenotypes providing mapping information to retrace donors / pools / stimulations. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-18T10:27:38.124295+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000141","title":"Investigating differential diagnostic and prognostic biomarkers in primary cutaneous follicle center lymphoma and follicular lymphoma using low-coverage whole-genome sequencing","description":"In this study, we analyzed 28 primary cutaneous follicle center lymphoma samples from 20 patients and compared the copy number profiles to a cohort of diagnostic samples of 64 nodal follicular lymphoma patients using low-coverage whole genome sequencing (lcWGS).","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-17T11:30:37.173751+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000142","title":"Multi-omics characterisation of immune cells in Long Covid","description":"We generated 10X Multiomics (paired RNA+ATAC) for Long Covid patients with up to 14 months follow-up.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-25T23:05:57.676794+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000143","title":"Multi-omics characterisation of the response to stimulation in Long Covid patients","description":"We stimulated immune cells of 15 patients (5 timepoints) with Long Covid with RPMI or P. Aeruginosa strains (4h stimulations). ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-25T23:05:59.491882+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000144","title":"Longitudinal dynamics of gene expression and metabolomics in an aging population cohort","description":"The MultiMuTHER study is a longitudinal study of 335 subjects seen at three or more clinical visits per participant. The MultiMuTHER study has:\r\n(1) identified genes and metabolites whose levels in whole blood changed over time \r\n(2) assessed the impact of environmental factors on molecular traits \r\n(3) investigated the cross-sectional and longitudinal relationships between genes and metabolites.\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-09T17:01:25.278502+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000145","title":"SCANDARE MACARON","description":"Among gynecological cancers, high-grade serous ovarian cancer has the highest prevalence and more than 75% of patients have advanced stage at diagnosis with a 5-year survival of 40%. When the initial complete surgical removal is not possible (60% of patients), an interval surgery can be considered after three to four cycles of neoadjuvant chemotherapy to reduce the tumor mass. However, in approximately 50% of cases the tumor has little or no response to neoadjuvant chemotherapy. Therefore, identification of potential drug targets, biomarkers and/or pathways whose modulation can help in the prevention, interception, or curing of the disease is essential to address the unmet need. Therefore, MACARON project aims to address these issues through the identification of shared neoantigens arising out of somatic alterations and aberrant transcriptional programs in ovarian cancer DNA/RNA datasets.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-26T17:21:48.957105+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000146","title":"Small‑scale mutations are infrequent as mechanisms of resistance in post‑PARP inhibitor tumour samples in high grade serous ovarian cancer","description":"Targeted DNA sequencing of high-grade serous ovarian cancer (HGSC) tumour and normal samples from 26 patients.\r\nFollowing target hybrid capture of 63 genes involved in DNA repair and response to treatment with an Agilent SureSelect XT panel, sequencing libraries were generated using the SureSelect XT Low Input Target Enrichment System (Agilent) as per the manufacturer's protocol. Libraries were sequenced on an Illumina NextSeq 500 at the Peter MacCallum Cancer Centre (Melbourne, Australia).","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-07T09:30:18.175716+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000147","title":"Heterogeneity and evolution of DNA mutation rates in microsatellite stable colorectal cancer. Higher mutation rates (MR) in metastatic tumours","description":"Building on the observation that MR appears to be a unique and inheritable feature of each cancer cell, we explored whether MR is subject to selective pressure during cancer progression. These data suggest that a higher MR is selected during CRC metastatic progression.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-06T16:46:40.246319+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000148","title":"Redefined indel taxonomy reveals insights into mutational signatures","description":"Despite their deleterious effects, small insertions and deletions (indels) have received far less attention than substitutions. Here we generated isogenic CRISPR-edited human cellular models of post-replicative repair dysfunction (PRRd), including individual and combined gene-edits of mismatch repair (MMR) and replicative polymerases (POLE and POLD1), enabling the study of mutational processes driving indel formation.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-06T11:16:03.612155+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000149","title":"The mutational landscape and its longitudinal dynamics in relapsed and refractory Hodgkin lymphoma ","description":"In classical Hodgkin-lymphoma (cHL), only a few cases recur, and only a limited fraction of patients is primary-refractory to standard-polychemotherapy. Underlying genomic features of unfavorable clinical courses remain sparsely characterized. Here, we investigated the genomic characteristics of primary-refractory/relapsed cHL in contrast with long-term-responders (LTR). In total, data from 84 samples were submitted. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-12T16:37:33.551152+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000150","title":"RNA-Seq analysis of cocaine use disorder in Brodmann Area 9","description":"We aimed to identify cocaine use disorder associated changes in gene expression in the Brodmann Area 9 subregion of the human prefrontal cortex. RNA-sequencing was performed in N=13 individuals with and N=12 individuals without CUD. The individuals are originating from a cohort of N=42 individuals where DNA methylation (DNAm) levels were previously analyzed using the EPIC array.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-06T12:35:59.685521+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000151","title":"Analysis of CD20 loss in patients treated with Mosunetuzumab","description":"CD20 is an established therapeutic target in B-cell malignancies. The CD20xCD3 bispecific antibody mosunetuzumab has significant efficacy in B-cell non-Hodgkin lymphomas (NHL). Since target antigen loss is a recognized mechanism of resistance, we evaluated the contribution of CD20 expression to clinical response in patients with relapsed and/or refractory NHL in the phase 1/2 GO29781 trial (ClinicalTrials.gov: NCT02500407) investigating mosunetuzumab monotherapy. CD20 was studied using immunohistochemistry (IHC), RNA sequencing, and whole-exome sequencing performed centrally in biopsies collected prior to treatment, or as paired samples at pre-dose and on-treatment, or at-progression. Prior to treatment, most patients exhibited a high proportion of tumor cells expressing CD20; however, the proportion of CD20+ tumor cells in 14/293 (6%) patients was &lt;10%. Analyses of paired biopsies from patients during treatment revealed that CD20 levels were maintained in 29/30 (97%), vs patients with samples at-progression, in which 11/32 (34%) showed CD20 loss. Reduced transcription or acquisition of truncating mutations explained most but not all cases of CD20 loss. In vitro modeling confirmed the effect of CD20 variants identified in clinical samples on reduction of CD20 expression and confirmed missense mutations in the extracellular domain that could block mosunetuzumab binding. This study expands knowledge about the occurrence of target antigen loss after anti-CD20 therapeutics to CD20-targeting bispecific antibodies and elucidates the underlying mechanisms for reduced CD20 expression at disease progression that may be generalizable to other anti-CD20 targeting agents. These results also establish the utility of readily-available IHC staining for CD20 as a tool to inform clinical decisions.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-16T13:10:56.053629+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000152","title":"Eribulin efficacy in platinum-resistant and refractory high-grade serous ovarian cancer patient-derived xenograft models","description":"Objectives: To determine the potential of anti-microtubule agent (AMA) therapy (paclitaxel, vinorelbine and eribulin) in platinum-resistant or refractory (PRR) HGSC by assessing response in patient-derived xenograft (PDX) models of HGSC.\r\nApproach:We characterized a cohort of PRR HGSC PDX models generated from treatment naïve or postsystemic therapy specimens, representative of individuals with PRR HGSC in the clinic.\r\nWhole-exome sequencing was carried out on five PDX tumours and whole-genome sequencing was carried out on one patient tumour.\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-02T11:17:31.578282+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000153","title":"Sample Multiplexing Oligo Comparison","description":"In this study, we compared various multiplexing reagents, including MULTI-Seq, Hashtag antibody, and CellPlex, in patient-derived xenografts (PDXs). We found that all multiplexing reagents worked well in cell types robust to ex vivo manipulation but suffered from signal-to-noise issues in more delicate sample types. We also compared the performance of fixed scRNA-Seq kits and CRISPR-based destruction of non-informative genes.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-02T11:17:33.264692+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000154","title":"Genome-wide NanoRCS sequencing of cfDNA and ctDNA from liquid biopsies of healthy individuals and cancer patients","description":"Levels of circulating tumor DNA (ctDNA) in liquid biopsies may serve as a sensitive biomarker for real-time, minimally-invasive tumor diagnostics and monitoring. However, detecting ctDNA is challenging, as much fewer than 5% of the cell-free DNA in the blood typically originates from the tumor. To detect lowly abundant molecules, extremely sensitive sequencing methods are required. We developed a new technique, NanoRCS, which is based on Oxford Nanopore sequencing of concatenated copies of a single DNA molecule for genome-wide sequencing, and applied this to plasma of healthy individuals, Esophageal cancer patients and  Granulosa cell tumor patients and ascites of Ovarian cancer patients. We also sequenced these samples on Illumina Novaseq, to compare the two techniques.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-06T18:07:33.767296+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000155","title":"Epigenomic atlas of organoid development","description":"To investigfate the epigenomic basis of fate decisions in the central nerveous system, we recorded a epigenomic timecourse of human brain organoid development using Cut&Tag with paired scRNA-seq. We further performed perturbation experiment inhibiting EED and profiled the response with scRNA-seq and Cut&Tag. Finally, we profiled a sample of the developing human brain using multiome sequencing and Cut&Tag. In our study, we uncover epigenomic switches during brain region diversification and show that epigenetic activation precedes gene expression during neurogenesis in organoids and in primary tissue. Lastly, we show that transcriptional repression by H3K27me3 is required to stabilize neuroectoderm induction from pluripotency.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-25T15:36:05.803249+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000156","title":"Transcriptome of CD4+ T cells and CD8+ T cells in glioblastoma multiforme","description":"Patients included in this study were over 18 years of age and had a histology-confirmed diagnosis of glioblastoma multiforme (GBM). Exclusion criteria were the previous administration of any anti-tumor therapy including radiation therapy. All patients gave written informed consent. The study was approved by the local ethics committee (TUM Medical school) and conducted following the Declaration of Helsinki. During resection of the tumors, tumor tissue and tissue from normal appearing brain within the operative channel was collected. Blood was drawn during the surgical procedure. Single cell suspensions were prepared from the tumor tissue, the normal appearing brain, and the blood. CD4+ T cells and CD8+ T cells were sorted by flow cytometry. Only patients with a complete set of specimens (CD4+ tumor infiltrating lymphocytes (TIL), CD8+ TIL, CD4+ T cells from normal appearing brain, CD8+ T cells from normal appearing brain, blood-derived CD4+ and CD8+ T cells) containing a minimum of 1000 cells in each sorted sample were further analyzed (n=9). Total RNA was isolated from sorted cell populations using the RNAeasy Plus micro kit (Qiagen, 74034). Quality and integrity of total RNA was controlled on a Bioanalyzer 2100 (Agilent Technologies). Library preparation for bulk-sequencing of poly(A)-RNA was done as described previously (Parekh et al., 2016). Briefly, barcoded cDNA of each sample was generated with a Maxima RT polymerase (ThermoFisher Scientific, EP0742) using oligo-dT primer containing barcodes, unique molecular identifiers (UMIs) and an adaptor. Ends of the cDNAs were extended by a template switch oligo (TSO) and full-length cDNA was amplified with primers binding to the TSO-site and the adaptor. NEB UltraII FS kit was used to fragment cDNA. After end repair and A-tailing, a TruSeq adapter was ligated and 3'-end-fragments were finally amplified using primers with Illumina P5 and P7 overhangs. In comparison to previous descriptions (Parekh et al., 2016), the P5 and P7 sites were exchanged to allow sequencing of the cDNA in read 1 and barcodes and UMIs in read 2 to achieve a better cluster recognition. The library was sequenced on a NextSeq 500 (Illumina) with 59 cycles for the cDNA in read 1 and 16 cycles for the barcodes and UMIs in read 2. Data were processed using the published Drop-seq pipeline (v1.0) to generate sample- and gene-wise UMI tables (Macosko et al., 2015). Reference genome (GRCh38) was used for alignment. Transcript and gene definitions were used according to the Genecode Annotation Version 35.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-29T16:45:15.085166+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000157","title":"Small RNA sequencing of human oocytes and early embryos","description":"This study looks at small RNA expression in human oocytes (n=12), zygotes (n=5), and embryos (n=10). The sample preparation and sequencing were done in two batches. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[34340992],"external_links":null,"is_released":true,"released_date":"2024-05-17T13:34:01.824823+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000158","title":"Oxidative DNA damage and ubiquitin proteasome system dysfunction underpins neurodegeneration in young adults with a DNA repair disorder","description":"Xeroderma pigmentosum (XP) is caused by defective nucleotide excision-repair of DNA damage. This results in hypersensitivity to ultraviolet light and increased skin cancer risk, as sunlight-induced photoproducts remain unrepaired. However, many XP patients also display early-onset neurodegeneration, which leads to premature death. The mechanism of neurodegeneration is unknown. Here, we investigate XP neurodegeneration using pluripotent stem cells derived from XP patients and healthy relatives, performing functional multi-omics on samples during neuronal differentiation. We have identified substantially increased levels of 5',8-cyclopurine and 8-oxopurine in XP neuronal DNA secondary to marked oxidative stress. Furthermore, we find endoplasmic reticulum stress is upregulated, and, critically, XP neurons exhibit inappropriate downregulation of the protein clearance ubiquitin-proteasome system (UPS). Chemical enhancement of UPS activity improves phenotypes, albeit inadequately, implying that early detection/prevention strategies are necessary to produce clinically impactful outcomes. Thus, we develop an early detection assay predicting neurodegeneration in at-risk patients.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-06T11:16:08.897766+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000159","title":"ScRNA-seq of human kidney immune cells of patients with ANCA-associated glomerulonephritis, Lupus Nephritis against a \"healthy\" nephrectomy control","description":"ANCA-associated glomerulonephritis (AGN) associates with a high risk of end-stage kidney disease. The role of kidney immune cells in local inflammation remains unclear. Here, we investigate kidney immune cell diversity and function. Kidney tissue from AGN patients (n=5) and a lupus nephritis (LN) patient (n=1) were aquired during a biopsy procedure for a clinical indication. Needle-core biopsies were obtained for histopathological examination, and an additional pass was performed to retrieve kidney tissue for scRNA-seq. Healthy kidney tissue (n=1) was obtained from a kidney that was surgically removed do tue due  to a (non-invasive) papillary urothelial carcinoma. Immediately after collection, kidney tissue was processed into a single-cell suspension and sorted using a 4-color flow cytometry panel to isolate living, CD45+ immune cells. To aid in the multi-omic characterization, surface markers and T and B cell repertoires were sequenced in 2 samples (1 AGN patient and the nephrectomy control). These samples were incubated with an oligo-antibody TotalSeq-C cocktail containing 130 unique cell surface antigens.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-10T17:12:46.544037+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000160","title":"Oxidative DNA damage and ubiquitin proteasome system dysfunction underpins neurodegeneration in young adults with a DNA repair disorder","description":"Xeroderma pigmentosum (XP) is caused by defective nucleotide excision-repair of DNA damage. This results in hypersensitivity to ultraviolet light and increased skin cancer risk, as sunlight-induced photoproducts remain unrepaired. However, many XP patients also display early-onset neurodegeneration, which leads to premature death. The mechanism of neurodegeneration is unknown. Here, we investigate XP neurodegeneration using pluripotent stem cells derived from XP patients and healthy relatives, performing functional multi-omics on samples during neuronal differentiation. We have identified substantially increased levels of 5',8-cyclopurine and 8-oxopurine in XP neuronal DNA secondary to marked oxidative stress. Furthermore, we find endoplasmic reticulum stress is upregulated, and, critically, XP neurons exhibit inappropriate downregulation of the protein clearance ubiquitin-proteasome system (UPS). Chemical enhancement of UPS activity improves phenotypes, albeit inadequately, implying that early detection/prevention strategies are necessary to produce clinically impactful outcomes. Thus, we develop an early detection assay predicting neurodegeneration in at-risk patients.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-06T11:16:05.404043+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000161","title":"Clonally heritable gene expression imparts a layer of diversity within cell types","description":"Cell types can be classified according to shared patterns of transcription. Non-genetic variability among individual cells of the same type has been ascribed to stochastic transcriptional bursting and transient cell states. Using high coverage single cell RNA profiling, we asked whether long-term, heritable differences in gene expression can impart diversity within cells of the same type. Studying clonal human lymphocytes and mouse brain cells, we uncovered a vast diversity of heritable gene expression patterns among different clones of cells of the same type in vivo. We combined chromatin accessibility and RNA profiling on different lymphocyte clones to reveal thousands of regulatory regions exhibiting interclonal variation which could be directly linked to interclonal variation in gene expression. Our findings identify a source of cellular diversity, which may have important implications for how cellular populations are shaped by selective processes in development, aging and disease.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-19T12:47:45.426999+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000162","title":" Oxidative DNA damage and ubiquitin proteasome system dysfunction underpins neurodegeneration in young adults with a DNA repair disorder","description":"Xeroderma pigmentosum (XP) is caused by defective nucleotide excision-repair of DNA damage. This results in hypersensitivity to ultraviolet light and increased skin cancer risk, as sunlight-induced photoproducts remain unrepaired. However, many XP patients also display early-onset neurodegeneration, which leads to premature death. The mechanism of neurodegeneration is unknown. Here, we investigate XP neurodegeneration using pluripotent stem cells derived from XP patients and healthy relatives, performing functional multi-omics on samples during neuronal differentiation. We have identified substantially increased levels of 5',8-cyclopurine and 8-oxopurine in XP neuronal DNA secondary to marked oxidative stress. Furthermore, we find endoplasmic reticulum stress is upregulated, and, critically, XP neurons exhibit inappropriate downregulation of the protein clearance ubiquitin-proteasome system (UPS). Chemical enhancement of UPS activity improves phenotypes, albeit inadequately, implying that early detection/prevention strategies are necessary to produce clinically impactful outcomes. Thus, we develop an early detection assay predicting neurodegeneration in at-risk patients.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-06T11:16:07.144125+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000163","title":"Longitudinal copy number variation analysis from plasma DNA of head and neck cancer patients under re-radiotherapy","description":"Recurrent locally advanced head and neck cancer (HNC) patients, receiving re-radiotherapy (re-RT), are presented with short progression-free (PFS) and overall survival. Hence, biomarkers predicting therapy failure are urgently needed.\r\nWe analyzed copy number variations (CNVs) in blood plasma of HNC patients collected before, during and after re-RT. Detectable CNVs after five and ten fractions of re-irradiation as well as at the end of re-RT were associated with short PFS. Furthermore, we found that CNV kinetics in longitudinally collected plasma reflected therapy response and could detect disease progression in advance of radiographic tumor assessments.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-02T08:38:51.251104+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000164","title":"Mapping Genotypes to Chromatin Accessibility Profiles in Single Cells","description":"In somatic tissue differentiation, chromatin accessibility changes govern priming and precursor commitment towards cellular fates1–3. Therefore, somatic mutations likely alter chromatin accessibility patterns, as they disrupt differentiation topologies leading to abnormal clonal outgrowth. However, defining the impact of somatic mutations on the epigenome in human samples is challenging due to admixed mutated and wild-type cells. To chart how somatic mutations disrupt epigenetic landscapes in human clonal outgrowths, we developed Genotyping of Targeted loci with single-cell Chromatin Accessibility (GoT-ChA). This high-throughput platform links genotypes to chromatin accessibility at single-cell resolution, across thousands of cells within a single assay. We applied GoT-ChA to CD34+ cells from myeloproliferative neoplasm (MPN) patients with JAK2V617F-mutated hematopoiesis.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-15T10:49:03.96286+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000165","title":"scRaCH-seq fastq files","description":"We base called the raw data of nanopore sequencing using the Guppy software (v3.1.5) with “dna_r9.4.1_450bps_sup_prom.cfg” configuration. The passed reads (Qscore > 9) are deposited in this EGA study.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-23T12:45:52.624478+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000166","title":"Nanopore sequencing enables allelic phasing of FLG loss-of-function variants, intragenic copy number variation and methylation status in atopic dermatitis and ichthyosis vulgaris","description":"Loss-of-function (LoF) variants in the FLG gene are associated with ichthyosis vulgaris (IV) and atopic dermatitis (AD). IV and AD patients with two FLG LoF variants are reported to have a more severe disease course. However, subsets of compound heterozygous patients display phenotypic heterogeneity despite a prediction of a severe phenotype from their genotype. The underlying genetic mechanism of this phenotypic variability is unknown. One possibility is that two LoF FLG variants could be located in cis (on the same allele), thus altering the predicted gene dosage. To investigate the allelic contribution of compound heterozygous FLG LoF mutations to IV phenotypic variability, we employ long reads from Oxford Nanopore Technologies, utilising two methodologies to phase the entire coding region of FLG into parental alleles: an amplicon-sequencing approach and an adaptive-sampling strategy. We investigated the allelic phasing of FLG LoF variants and intragenic-repeat copy-number variations (CNV) of 21 subjects with known compound heterozygous genotypes and mixed IV severity. Our results suggest that IV severity is not linked to the presence of cis variants in our IV patient cohort. Nanopore reads enabled detection and accurate phasing of CNVs and LoF variants into parental alleles, providing a framework for future in-depth genetic analysis. These results highlight the usefulness of utilising long reads for interrogating the FLG gene and other highly repetitive genes for genetic stratification related to clinical phenotypes.\r\n","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-06T11:31:58.337071+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000167","title":"Origin of second malignancies in children","description":"Pediatric cancers are rare diseases, and children without known germline predisposing conditions who develop a second malignancy during developmental ages are extremely rare. We present four such clinical cases and through whole-genome and error-correcting ultra-deep duplex sequencing of tumor and normal samples, we explored the origin of the second malignancy in four children, uncovering different routes of development. The exposure to cytotoxic therapies was linked to the emergence of a secondary AML. A common somatic mutation acquired early during embryonic development was the driver of two solid malignancies in another child. In two cases, the two tumors developed from completely independent clones diverging during embryogenesis. Importantly, we demonstrate that platinum-based therapies contributed at least in one order of magnitude more mutations per day of exposure than aging to normal tissues in these children.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-06T11:25:32.506828+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000168","title":"Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial","description":"Gastric and gastroesophageal junction (G/GEJ) cancers carry a poor prognosis, and despite recent advancements most patients die of their disease. While immune checkpoint blockade has become part of the standard of care for patients with metastatic G/GEJ cancers, its efficacy and impact on the tumor microenvironment in the early disease setting remain largely unknown. We hypothesized a higher efficacy of neoadjuvant immunotherapy plus chemotherapy in patients with non-metastatic G/GEJ cancer. In the phase 2 PANDA trial, patients with previously untreated resectable G/GEJ tumors (n=21) received neoadjuvant treatment with one cycle of atezolizumab monotherapy followed by 4 cycles of atezolizumab plus docetaxel, oxaliplatin and capecitabine. Treatment was well-tolerated, and all patients underwent resection without treatment-related delays, meeting the primary endpoint of safety and feasibility. Tissue was obtained at multiple time points, allowing analysis of the effects of single-agent PD-L1 blockade and the subsequent combination with chemotherapy on the tumor microenvironment. A total of 21 patients were included, of whom 20 patients underwent surgery and were evaluable for the secondary pathologic response and survival endpoints, while 19 were evaluable for exploratory translational analyses. A major pathologic response (MPR, ≤10% residual viable tumor) was observed in 14/20 (70%; 95% CI 46-88%) patients, including 9 (45%; 95% CI 23-68%) pathologic complete responses. At a median follow-up of 47 months, 13/14 responders were alive and disease-free, while 5/6 nonresponders had died due to disease recurrence. Notably, baseline PD-1+CD8+ T cell infiltration was significantly higher in responders than in nonresponders, and comparison of the tumor microenvironment alterations following anti-PD-L1 monotherapy versus the subsequent combination with chemotherapy revealed that increased immune activity was achieved upon single-agent PD-1/L1 axis blockade. Based on these data, anti-PD-L1 plus chemotherapy warrants further exploration in patients with non-metastatic G/GEJ cancer, and these results call for validation in a larger cohort.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-01-29T10:38:35.667586+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000169","title":"Evolutionary Trajectories of Small Cell Lung Cancer under Therapy","description":"Small cell lung cancer (SCLC) is one of the deadliest human cancers with a five-years survival rate of less than 7%. The standard of care for extensive-stage SCLC consists of systemic treatment with platinum and etoposide, recently combined with PD-L1 immune checkpoint inhibitors (ICI). SCLC patients show high sensitivity to platinum-based chemotherapy, followed by rapid recurrence, which distinguishes SCLC from most human cancers. Unfortunately, second-line treatment with other chemotherapeutics or immunotherapy is only marginally effective, and patients ultimately succumb to their disease. \r\n\r\nWe performed whole exome sequencing, whole genome sequencing and transcriptome sequencing of multiple tumor regions from 65 patients with SCLC. We determined tumor phylogenies at diagnosis and throughout chemotherapy and immunotherapy by multi-region sequencing of 160 tumors from 65 patients, to thus decipher the evolutionary processes underlying the remarkable sensitivity of small cell lung cancer (SCLC) to chemotherapy.\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-05T15:05:36.34029+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000170","title":"CRCbiome: Gut metagenome of Norwegian screening participants using FIT sampling","description":"The study aims to characterize the gut metagenome of Norwegian screening participants and assess the ability of the gut metagenome to identify those at need for colonoscopy.\r\n\r\nBackground: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. Methods: The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50–74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. Discussion: The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-01T14:07:30.056845+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000171","title":"Exome sequencing of patient samples from study","description":"Exome sequencing data from FFPE preserved patient samples and patient-derived cultures. The goal of the study is to validate patient-derived cultures. Additional goal is to understand the relationship between omics and drug response.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-01T12:04:39.490707+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000172","title":"Whole transcriptome seq from patient samples","description":"Exome sequencing data from FFPE preserved patient samples and patient-derived cultures. The goal of the study is to validate patient-derived cultures. Additional goal is to understand the relationship between omics and drug response.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-01T12:04:41.837129+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000173","title":"Single-cell transcriptomic analyses of peripheral blood mononuclear cells, peritoneal fluid, and peritoneal metastases from patients with colorectal cancer","description":"The data published here contains single-cell RNA- sequencing (scRNAseq) on peripheral blood mononuclear cells (PBMC), peritoneal fluid (PF), and peritoneal metastases (PM). PBMC, PF and, where possible, PM was acquired from patients with colorectal cancer (CRC) and subjected to 3' scRNAseq using the 10X Genomics (Chromium Single Cell 3’ Reagent). Sequencing was performed in a paired-ended fashion on either the HiSeq4000 or the NovaSeq6000.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-05T16:37:40.180949+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000174","title":"Single-cell RNA-sequencing and cellular indexing of transcriptomes and epitopes of peripheral blood mononuclear cells and peritoneal fluid from patients with achalasia","description":"The data published here contains cellular indexing of transcriptomes and epitopes (CITE-seq) and single-cell RNA- sequencing (scRNAseq) data on patients with achalasia. Paired PBMC and PF were subjected to 3' scRNAseq and CITE-seq, respectively. All single-cell data was generated using the 10X Genomics (Chromium Single Cell 3’ Reagent) and sequenced in a paired-ended fashion on the NovaSeq6000.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-05T16:37:45.539116+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000175","title":"Harnessing Epigenetic Regulators to improve HSC-based lentiviral gene therapy","description":"Curative benefits of autologous and allogeneic transplantation of hematopoietic stem cells (HSCs) have been proven for various diseases. However, the low number of true HSCs that can be collected from patients and subsequently in vitro maintenance and expansion of true HSCs for genetic correction remain challenging. Addressing this issue, we here focused on optimizing culture conditions to improve the ex vivo expansion of true HSCs for gene therapy purposes. In particular, we explore the use of epigenetic regulators to enhance the effectiveness of HSC-based lentiviral (LV) gene therapy. The HDAC inhibitor Quisinostat and the bromodomain inhibitor CPI203 each promote ex vivo expansion of functional HSCs, as validated by xenotransplantation assays and single cell RNA-sequencing analysis. We confirmed the stealth effect of LV transduction on the loss of HSC numbers in commonly used culture protocols, while addition of Quisinostat or CPI203 improved expansion of HSCs in transduction protocols. Of note, we demonstrated that addition of Quisinostat improved LV transduction efficiency of HSCs and early progenitors. Our suggested culture conditions highlight the potential therapeutic effect of epigenetic regulators in hematopoietic stem cell biology and their clinical applications to advance HSC-based gene correction.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000176","title":"Induced pluripotent stem cell derived pericytes respond to mediators of proliferation and contractility","description":"Differentiation of mesoderm pericytes from induced pluripotent stem cell lines. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-09T14:43:44.68366+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000177","title":"Arcagen – Cancer of unknown Primary domain","description":"Arcagen is an EORTC/SPECTA pan-European project that aims to recruit 1000 rare cancer patients from different tumour domains of EURACAN. This study collected samples from advanced or metastatic rare cancer from patients older than 12, and analysed them using Foundation Medicine next-generation sequencing (NGS) panels (FoundationOne CDx for FFPE samples or FoundationOne Liquid CDx for blood samples). Here we are submitting the dataset that contain NGS files patients diagnosed with a locally advanced or metastatic Cancer of Unknown Primary (n=96).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-02T14:12:10.976672+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000178","title":"Analysis of cell type contributions to cell free DNA in health and disease.","description":"This study looks at cell type contributions to cell free DNA in health and disease.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-12T13:56:32.267606+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000179","title":"Stability of gut microbiome after COVID-19 vaccination in healthy and immuno-compromised individuals","description":"Bidirectional interactions between the immune system and the gut microbiota are key contributors to various physiological functions. Immune-associated diseases such as cancer and auto- immunity, and efficacy of immunomodulatory therapies, have been linked to microbiome variation. Although COVID-19 infection has been shown to cause microbial dysbiosis, it remains understudied whether the inflammatory response associated with vaccination also impacts the microbiota. Here, we investigate the temporal impact of COVID-19 vaccination on the gut microbiome in healthy and immuno-compromised individuals; the latter included patients with primary immunodeficiency and cancer patients on immuno- modulating therapies. We find that the gut microbiome remained remarkably stable postvaccination irrespective of diverse immune status, vaccine response, and microbial composition spanned by the cohort. The stability is evident at all evaluated levels including diversity, phylum, species, and functional capacity. Our results in- dicate the resilience of the gut microbiome to host immune changes triggered by COVID-19 vaccination and suggest minimal, if any, impact on microbiome-mediated processes. These findings en- courage vaccine acceptance, particularly when contrasted with the significant microbiome shifts observed during COVID-19 infection.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-02T13:27:39.327884+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000180","title":"The assessment of genetic and immunological backgrounds in advanced NSCLC patients treated with immunotherapy","description":"Non-small-cell lung cancer treatment relies greatly on immunotherapy. Both programmed death ligand 1 expression on tumour cells and tumour mutational burden are used to predict the response to such treatment and qualify patients for the therapy, but in some cases, those biomarkers do not perform well enough. Discovering new markers indicating resistance or response to immunotherapy would therefore allow clinicians to modify therapy course for the benefit of the patient. This paper is aimed at describing the genetic and immunological background of immunotherapy courses and discovering factors possibly related to clinical benefit or lack of response, using next-generation sequencing of tumour tissue and flow cytometry analysis of lymphocyte subpopulations in peripheral blood of non-small cell lung cancer patients.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000181","title":"Single cell transcriptomics in expanded Tregs of APS-1 patients","description":"Aim of study: \r\nExploring single cell transcriptomics in expanded Tregs of with autoimmune polyendocrine syndrome type 1 (APS-1) patients (global gene expression, immune panel, TCR). N= 9 APS-1 patients and 9 healthy controls\r\n\r\nProtocol\r\n1. Regulatory T cells (Tregs) were isolated from EDTA-blood, activated with anti-CD3/CD28 and IL2, expanded in cell culture for 14 days and stored at -150℃ in AB serum or FBS + 5% DMSO until use.\r\n2. Cells were thawed, run through a Live/Dead column and carefully counted. 10000 Tregs were used as input for the 10x protocol.  \r\n3. cDNA was generated and amplified using Single Cell VDJ 5’ Gel Beads, Chromium Next GEM Chip K Single cell Kit, Next GEM Single Cell 5’ GEM Kit v2 and 5’ Feature Barcode Kit (all from 10x genomics).\r\n4. Gene expression (GEX) libraries were generated by using the Library Construction Kit from 10x genomics.\r\n5. T-cell receptor (TCR) libraries were generated using the Single Cell Human TCR Amplification Kit and the Library Construction Kit from 10x genomics.\r\n6. 10x Genomics Target Hybridization Kit and Human Immunology Panel was used with GEX libraries.  Only 8 patient samples and 8 control samples were used for the immune panel.\r\n7. All libraries have a unique sample index (Dual Index TT Set A). \r\n8. All samples were sequenced on Illumina NovaSeq 6000 on a NovaSeq S2 flow cell. \r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-22T08:44:37.039493+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000182","title":"Spatial and temporal transcriptome analysis on human skeletal muscle regeneration","description":"Skeletal muscle carries a unique ability for adaptation as well as regeneration that highly depends on a supportive cellular microenvironment. Here we show that spatial and single-cell transcriptomic analysis in human skeletal muscle is a unique approach to illuminate cellular interactions in the microenvironment. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-26T15:26:19.591278+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000183","title":"An isoform quantitative trait locus in SBNO2 links genetic susceptibility to Crohn’s disease with defective antimicrobial activity","description":"Despite major advances in linking single genetic variants to single causal genes, the significance of genetic variation on transcript-level regulation of expression, transcript-specific functions, and relevance to human disease has been poorly investigated. Strawberry notch homolog 2 (SBNO2) is a candidate gene in a susceptibility locus with different variants associated with Crohn’s disease and bone mineral density. The SBNO2 locus is also differentially methylated in Crohn’s disease but the functional mechanisms are unknown. Here we show that the isoforms of SBNO2 are differentially regulated by lipopolysaccharide and IL-10. We identify Crohn’s disease associated isoform quantitative trait loci that negatively regulate the expression of the noncanonical isoform 2 corresponding with the methylation signals at the isoform 2 promoter in IBD and CD. The two isoforms of SBNO2 drive differential gene networks with isoform 2 dominantly impacting antimicrobial activity in macrophages. Our data highlight the role of isoform quantitative trait loci to understand disease susceptibility and resolve underlying mechanisms of disease.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-22T10:49:48.14095+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000184","title":"Transcriptomic analysis of LINE1 expression in the human brain","description":"Twist Biosciences probes were designed to enrich LINE1 and HERV sequences from human brain cDNA libraries. Postmortem human prefrontal cortex and temporal cortex samples from non-diseased controls and Alzheimer's disease were used. Enriched cDNA libraries were sequenced on a PacBio Sequel II (15-16 samples per SMRTCell).","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-16T13:18:21.581775+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000185","title":"Exome sequencing of early and late passage Patient Derived Xenogratf Tumoroids with matched Patient Derived Xenogratfs and matched normal liver","description":"The breadth and depth at which cancer models are interrogated contribute to successful translation of drug discovery efforts to the clinic. In colorectal cancer (CRC), model availability is limited by a dearth of large-scale collections of patient-derived xenografts (PDXs) and paired tumoroids from metastatic disease, the setting where experimental therapies are typically tested. XENTURION is a unique open-science resource that combines a platform of 129 PDX models and a sister platform of 129 matched PDX-derived tumoroids (PDXTs) from patients with metastatic CRC, with accompanying multidimensional molecular and therapeutic characterization. This specific dataset is focused on a comparison of early and late passage tumoroids transcriptomes. In this study we focused our attention on early (passage 3) and late (passage 8-12) PDXTs with their matched PDXs and normal liver","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-22T14:07:17.619133+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000186","title":"Raw sequencing files from WGS and RNA-Seq","description":"Acute leukemias are the most common malignancies in children with an onset of the disease among 0-6 years-old. The early development of theses malignancies has been proposed as an indicator of their prenatal origin, hypothesis that has been confirmed especially in the case of acute lymphoblastic leukemia. For acute myeloid leukemia (AML), comprising an heterogenous group of different cytogenetics subtypes, this prenatal origin has also been confirmed specially for MLL-rearranged and t(8;21) subgroups. AMLs carrying t(7;12) constitute up to 30% of cases under 2-years-old, frequently being associated with a trisomy of chromosome 19 and an overexpression of MNX1 gene. An in utero origin of this specific subgroup has been suggested but not clearly confirmed. Here, we present the case of a 5-months-old AML patient with t(7;12) in which we have fully characterized a novel breakpoint occurring among ETV6 and NOM1 genes. We demonstrate the presence of this specific ETV6-NOM1 fusion in CD34+ hematopoietic stem and progenitor cells isolated from the cord blood unit from the same patient and stored at birth. Moreover, trisomy +19 present at diagnosis was not detected at birth. Together, our results demonstrate the prenatal origin of the t(7;12) in infant AML, and establish trisomy +19 as a secondary event in this leukemia.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[38806630],"external_links":null,"is_released":true,"released_date":"2025-01-10T11:39:07.477924+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000187","title":"nanoCUSA","description":"This study aims to provide raw nanopoore sequencing data from tumor samples obtained during neurosurgery using a Cavitating Ultrasonic Aspirator. Acquired data with a subsequent neural network classifier with nanopore-specific diagnostic score thresholds assures high specificity while achieving acceptable sensitivity. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-22T17:25:14.09098+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000188","title":"Evaluation of the Efficacy and Safety of a Clinical Grade Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Patch: A Pre-Clinical Study","description":"Cardiomyocyte-derived induced pluripotent stem cells (iPSCs) may represent a promising therapeutic strategy for severely damaged myocardium. This study aimed to assess the efficacy and safety of clinical grade human iPSC-derived cardiomyocyte (hiPSC-CM) patches and conduct a pre-clinical proof-of-concept analysis.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-23T15:43:33.157041+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000189","title":"Evaluation of the Efficacy and Safety of a Clinical Grade Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Patch: A Pre-Clinical Study","description":"Cardiomyocyte-derived induced pluripotent stem cells (iPSCs) may represent a promising therapeutic strategy for severely damaged myocardium. This study aimed to assess the efficacy and safety of clinical grade human iPSC-derived cardiomyocyte (hiPSC-CM) patches and conduct a pre-clinical proof-of-concept analysis.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-23T15:43:33.157041+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000190","title":"EOSC4Cancer Synthetic Colorectal Cancer Genomic data","description":"In this study there are stored the synthetic datasets produced by partners involved in EOSC4Cancer. The study contains independent datasets available for the research community. The synthetic genomes have been created trying to mimic real cancer data.","abstract":null,"study_type":"Synthetic Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-09T13:26:32.119432+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000191","title":"Shallow Whole Genome Sequencing of Patient Derived Xenografts","description":"Chemotherapy is the standard-of-care treatment for metastatic colorectal cancer (mCRC) and benefits some patients, but what distinguishes responders from non-responders is unclear. In this study, we leveraged a comprehensive collection of 27 molecularly annotated patient-derived xenografts to uncover functional predictors of response to 5-FU and irinotecan combination therapy (FOLFIRI) in mCRC. Genetic analyses revealed that treatment sensitivity was marked by genomic scars indicative of BRCAness, suggesting homologous recombination (HR) deficiency as a key determinant. Accordingly, we surveyed a manually curated panel of 44 genes with a documented role in HR for the potential presence of pathogenic mutations. We did not observe a specific enrichment of HR gene mutations based on response to FOLFIRI. This result, combined with the absence of widespread biallelic inactivation of the analyzed genes and the predominance of mutations categorized as variants of unknown significance, suggests that FOLFIRI sensitivity is not primarily governed by underlying mutations in HR genes responsible for mitigating the genotoxic effects of this therapeutic regimen.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-19T15:51:53.190531+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000192","title":"Gene expression profiling of patient-derived fibroblasts with Maple Syrup Urine Disease (MSUD)","description":"Maple syrup urine disease (MSUD) is a rare inherited metabolic disorder characterized by deficient activity of the branched-chain alpha-ketoacid dehydrogenase (BCKD) complex, required to metabolize the amino acids leucine, isoleucine and valine. Despite its profound metabolic implications, the molecular alterations underlying this metabolic impairment had not yet been elucidated. We performed a comprehensive transcriptomic analysis on fibroblasts derived from a cohort of MSUD patients and unaffected controls to unravel the pathophysiology of MSUD.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000193","title":"Whole genome sequencing of PDAC tissues an PDOs","description":"whole genome sequencing (WGS) on 48 PDOs (established from 39 tumors) and 4 tissues samples. The majority of PDOs were established from treatment-naive and localized tumors. Histopathologically, the majority of PDAC tumors from which PDOs were established displayed a conventional morphological pattern, with two containing squamous components (defined as adenosquamous), and one classified as a signet-ring tumour.\r\n7 of the PDOs were grown in a culture medium lacking both WNT3A and RSPO1.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-03T10:36:11.650805+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000194","title":"CIRCLE-seq of PDAC PDO","description":"CIRCLE-seq was performed on a PDAC PDO to validate the presence and the structure of ecDNAs","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-03T10:36:17.746173+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000195","title":"Effect of AZD5582 treatment on transcriptomic of oral squamous cell carcinoma","description":"This dataset consists of the RNA-seq data of two AZD5582-sensitive OSCC cell lines - ORL-215, ORL-174 and two AZD5582-resistant OSCC cell lines - BICR10 and ORL-136, treated with either DMSO control or 10nM AZD5582 for 24 hours, in duplicates.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000196","title":"Long read transcriptome of DM1 patients whole blood","description":"DM1 is characterized by dysregulation of alternative mRNA splicing, to an quantitative as well as qualitative extend that is heterogenous between clinically similar patients. Hundreds of transcripts have been identified that can be misspliced in DM1, and for many of these it is still unclear whether they generate stable proteins in DM1 patients. We generated long-read transcriptome data of DM1 patients whole blood after hemoglobin depletion. Each sample is a mix of 5 patients of varying age.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-08T16:23:45.27924+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000197","title":"Enhanced resolution profiling in twins reveals differential methylation signatures of Type 2 Diabetes with links to its complications","description":"We profiled DNA methylation in blood samples from participants of European ancestry from 7 twin cohorts using a methylation sequencing platform targeting regulatory genomic regions encompassing 2,048,698 CpG sites. The results help to improve our understanding of T2D disease pathogenesis and progression and may provide biomarkers for its complications.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-25T15:09:26.63335+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000198","title":"Gut 16S rRNA/FINRISK 2002","description":"The main goal of the project is the study the associations between the gut 16S rRNA and human health. The dataset contains data for FINRISK 2002 participants (a random sample of individuals living in six geographic areas in Finland) who underwent fecal sampling.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-07T17:22:05.280708+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000199","title":"SAB demo study","description":"SAB demo","abstract":null,"study_type":"Epigenetics","pubmed_ids":[12345678],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000200","title":"RNA-seq of STIC lesions and adjacent normal samples","description":"In this study, we characterize premalignant lesions of the fallopian tube (serous tubal intraepithelial carcinomas) to explore the earliest events of tumorigenesis following mutation of the TP53 tumor suppressor gene. We conduct laser capture microdissection to isolate premalignant cells from adjacent normal cells, and subject isolated tissues to RNA-seq. Our findings reveal the earliest transcriptional changes established during premalignancy within the fallopian tube.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-17T10:24:07.187711+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000201","title":"Multi-cancer detection by immunological features derived from peripheral blood cell transcriptomes","description":"The utility of peripheral blood features other than cell-free DNA in noninvasive multi-cancer screening remains unexplored. Here, we developed a deep learning model that extracts cancer-specific immunological features from 10,929 tumor and 10,845 normal tissue transcriptomes. This model achieves an ROC-AUC of 0.94 in discriminating between our own 1,055 blood samples from various types of cancer and 745 normal blood samples. Its capability of cancer detection is not undermined by immunological perturbation resulting from checkpoint blockade therapy. Model interpretation unveils the significance of features pertaining to the B cell receptor repertoire. Coupled with our proof-of-concept model that distinguishes cancer from infectious or autoimmune conditions, this method achieves an ultimate ROC-AUC of 0.91 when applied to our separate test dataset comprising 183 cancer or normal samples. Our results highlight the clinical implications of local and peripheral immune characteristics in the application of blood-based multi-cancer detection. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000202","title":"PARK7/DJ-1 deficiency modulates microglial activation in response to LPS-induced inflammation","description":"Specific microglia responses are thought to contribute to the development and progression of various neurodegenerative diseases, including Parkinson’s disease (PD). However, the phenotypic acquisition of microglial cells and their role during the underlying neuroinflammatory processes remain largely obscure. Here, according to the multiple-hit hypothesis, which stipulates that PD etiology is determined by a combination of genetics and various environmental risk factors, we investigate microglial transcriptional programs and morphological adaptations under PARK7/DJ-1 deficiency, a genetic cause of PD, during lipopolysaccharide (LPS)-induced inflammation.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-03T16:17:56.867087+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000203","title":"The life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation","description":"Assessment of dexamethasone response in human lung through scRNA-seq analysis of bronchoalveolar lavage (BAL) samples from patients with severe COVID-19.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-02-26T14:44:33.173704+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000204","title":"Localised colon cancer WES study contaning WBCs, tissue and plasma samples at different time points","description":"Decision-making based on circulating tumor DNA (ctDNA) status following curative-intent surgery in stage II-III colon cancer (CC) is where the strongest clinical evidence lies. Commercial or academic assays are predominantly used to detect ctDNA, aiming to reveal minimal residual disease (MRD) and identify patients at high risk of recurrence. However, while current tests demonstrate exceptional specificity in detecting MRD among patients who later experience recurrence, their sensitivity is notably limited, particularly immediately after surgery when decisions regarding ACT are crucial. Additionally, up to 70% of patients with stage II-III colon cancer fail to clear ctDNA after standard adjuvant treatment (ACT) and subsequently experience recurrence. In this study, we performed whole exome sequencing (WES) of ctDNA at different timepoints in relapsed CC patients using two independent cohorts, alongside transcriptomic and proteomic analyses of metastases to gain a deeper understanding of progression mechanisms. An assay based on a tumor-agnostic approach from WES could enhance sensitivity in detecting MRD disease compared to current assays. Immune evasion appears to be the primary driver of progression in the localized CC setting, facilitated by a functional mutational burden at relapse. This suggests that immunotherapy could extend its efficacy to patients with microsatellite stability, broadening treatment options. Moreover, organoid modeling affirms the promising potential of targeted therapy to surpass conventional treatments in eradicating MRD.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-18T12:34:33.975004+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000205","title":"Colorectal cancer functional annotation - ATAC","description":"ATAC-seq data from multiple colorectal cancer cell lines","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-29T14:03:51.23694+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000206","title":"Colorectal cancer functional annotation - Micro-C","description":"Ultra high resolution Micro-C data from multiple colorectal cancer cell lines","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-29T14:03:47.856491+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000207","title":"Colorectal cancer functional annotation - ChIP","description":"ChIP-seq data for multiple colorectal cancer cell lines (H3K4me1, H3K4me3, H3K27ac, H3K27me3, H3K36me3, CTCF)","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-29T14:03:49.564611+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000208","title":"Colorectal cancer functional annotation - RNAseq","description":"RNA-seq data from multiple colorectal cancer cell lines","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-29T14:03:52.932985+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000209","title":"A Combined Omics and Tissue Biobank for Paediatric Cancers","description":"The Swedish Childhood Tumour Biobank (BTB) is a nonprofit national infrastructure for samples and genomic data collection from pediatric patients diagnosed with central nervous system and other solid tumours in Sweden. Fresh frozen tumour tissue and patient’s matched blood are collected from affected patients and genomic data is continuously generated and made available for approved medical research projects. We expect that the accessibility of biological samples and/or data to the research community will contribute to further advances in the understanding of tumour biology, which in turn will impact many aspects of clinical care of children with cancer, by refining diagnosis and/or identifying oncogenic drivers and therapeutic targets.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[37221626],"external_links":null,"is_released":true,"released_date":"2024-02-22T13:10:45.006077+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000210","title":"NGS-based monitoring of the T cell receptor repertoire in living donor kidney transplant patients undergoing combination cell therapy","description":"Tolerance induction through mixed chimerism is a promising approach to achieve long term graft patency without or only low dose maintenance immunosuppression. In this phase I/IIa  academic trial kidney transplant recipients in the case group were co-transplanted with bone marrow from the same donor and received an autologous cell product. The control group did not receive donor bone marrow or an autologous cell product. Peripheral blood mononuclear cells were collected at multiple timepoints before and after transplantation and the recipients native T-cell receptor (TCR) repertoire at time points 0, 1, 3 and 6 months after transplantation as well as their donor reactive TCR repertoire were analysed using NGS-based TCR sequencing.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-03T10:58:17.278138+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000211","title":"Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer","description":"No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility for risk stratification is unclear. Here, we intersect ctDNA%, treatment outcomes, and clinical characteristics across 738 plasma samples from 491 male mCRPC patients from two randomized multicentre phase II trials and a prospective province-wide blood biobanking program. ctDNA% correlates with serum and radiographic metrics of disease burden and is highest in patients with liver metastases. ctDNA% strongly predicts overall survival, progression-free survival, and treatment response independent of therapeutic context and outperformed established prognostic clinical factors. Recognizing that ctDNA-based biomarker genotyping is limited by low ctDNA% in some patients, we leverage the relationship between clinical prognostic factors and ctDNA% to develop a clinically-interpretable machine learning tool that predicts whether a patient has sufficient ctDNA% for informative ctDNA genotyping (available online: https://www.ctDNA.org). Our results affirm ctDNA% as an actionable tool for patient risk stratification and provide a practical framework for optimized biomarker testing.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-14T18:02:12.186833+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000212","title":"Improved detection of colibactin-induced mutations by genotoxic E. coli in organoids and colorectal cancer","description":"Co-culture of intestinal organoids with a colibactin-producing pks+ E. coli strain (EcC) revealed mutational signatures also found in colorectal cancer (CRC). E. coli Nissle 1917 (EcN) remains a commonly used probiotic, despite harboring the pks operon and inducing double strand DNA breaks. We determine the mutagenicity of EcN and three CRC-derived pks+ E. coli strains with an analytical framework based on sequence characteristic of colibactin-induced mutations. All strains, including EcN, display varying levels of mutagenic activity. Furthermore, a machine learning approach attributing individual mutations to colibactin reveals that patients with colibactin-induced mutations are diagnosed at a younger age and that colibactin can induce a specific APC mutation. These approaches allow the sensitive detection of colibactin-induced mutations in ~12% of CRC genomes and even in whole exome sequencing data, representing a crucial step towards pinpointing the mutagenic activity of distinct pks+ E. coli strains.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-11T17:53:37.224394+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000213","title":"T-ALL RNA-Seq raw data files","description":"Bone marrow or peripheral blood samples were collected of adult patients at first diagnosis of T-precursor acute lymphoblastic leukemia. RNA was isolated from mononuclear cells and subjected to mRNA library prep using Poly-A selection and sequencing on a NovaSeq 6000 system. Obtained gene expression profiles and gene fusion calls were used to allocate samples to molecular disease subtypes.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-30T10:25:20.715907+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000214","title":"Clonal Evolution and Blastic Plasmacytoid Dendritic Cell Neoplasm - Two Cases","description":"Here we present two case studies of sequential whole exome sequencing (WES) in patients, who both developed BPDCN throughout their medical history but primarily presented with lymphoid cancers (clonally related ALK-negative anaplastic large-cell lymphoma (ALCL) and T-lymphoblastic lymphoma (T-LBL)) and whose bone marrow at remission exhibited a CMML phenotype, from which in both cases BPDCN clones arose that subsequently became treatment refractory. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[38890446],"external_links":null,"is_released":true,"released_date":"2024-03-22T13:57:19.156285+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000215","title":"Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease","description":"Circulating tumor DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a NGS approach (Euroclonality-NDC), we evaluated clinical and prognostic value of ctDNA in a series of R-CHOP-treated DLBCL patients at baseline (n=68) and after 2-cycles (n=59), monitored by metabolic imaging (PET/CT).  \r\nA molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pre-treatment high ctDNA levels significantly correlated with elevated LDH, advanced stage, high risk IPI and a trend to shorter 2-year PFS. Valuable NGS data after 2-cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR vs. those not achieving MMR (2yr PFS of 76% vs. 0%, p<0.001). Similarly, more than 66% reduction in SUVmax by PET/CT identified two subgroups with different prognosis (2yr PFS of 83% vs. 38%; p<0.001). Combining both approaches MMR and SUVmax reduction, a better stratification was observed (2yr PFS of 84% vs. 17% vs. 0%, p<0.001).  \r\nEuroclonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at 2 cycles and its combination with interim PET results improves patient prognosis stratification.\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-07T17:19:01.440859+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000216","title":"DCLRE1B/Apollo germline mutations associated with renal cell carcinoma","description":"Highlights of Bories et al. article submitted to BBA - Molecular Basis of Disease: We identified 2 germline mutations in the DCLRE1B gene encoding the Apollo protein by Whole Exome Sequencing (WES) in two families with inherited clear-cell Renal Cell Carcinoma. Our study suggests a putative link between DNA repair, telomere protection and renal oncogenesis.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-28T13:52:36.851525+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000217","title":"Single-cell atlas of penile cancer reveals TP53 mutations as driver for an aggressive phenotype, irrespective of HPV status, and provides clues for treatment personalization","description":"Our aim was to identify molecular differences in the microenvironment of penile squamous cell carcinoma (PSCC) stratified by TP53 loss-of-function (TP53LOF) mutations and HPV-status. Hence, we present a first single-cell transcriptomic atlas of PSCC. Stratification based on TP53 and HPV-status uncovered differences in CSS and underlying molecular pathways. Our data indicate that TP53LOF tumors are characterized by worse biological behavior regardless of HPV-status. These findings and further research are essential for trial design in PSCC, allowing us to move away from the current one-size-fits-all approach.  ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-10T16:17:41.404223+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000218","title":"Homopolymer switches mediate adaptive mutability in mismatch repair-deficient colorectal cancer","description":"Study titled homopolymer switches mediate adaptive mutability in mismatch repair-deficient colorectal cancer","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-07T15:40:08.633092+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000219","title":"INVADE cohort","description":"Cohort of bulk RNAseq data from DCIS, invasive and microinvasive breast cancer at diagnosis. This dataset covers 18 DCIS cases, 17 microinvasive and 20 primary invasive breast cancer. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-07T17:55:30.655034+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000220","title":"Comprehensive spatial landscape and plasticity of immunosuppressive fibroblasts in breast cancer","description":"Although immunosuppressive and pro-metastatic functions of FAP+ Cancer-Associated Fibroblasts (CAF) are well-established, their plasticity and spatial distribution remain poorly understood. Here, we analyze trajectory inference, deconvolute spatial transcriptomics at single-cell level and perform functional assays to generate an integrative high-resolution map of breast cancer (BC), focusing particularly on the different subpopulations within inflammatory and myofibroblastic (iCAF/myCAF) FAP+ CAF. We identify 10 spatially-organized FAP+ CAF-related cellular niches, called EcoCellTypes, which are precisely localized within tumors. Consistent with their spatial organization, we identify DPP4- and YAP1-dependent mechanisms, by which cancer cells drive the transition of the detoxification-associated inflammatory FAP+ CAF cluster (Detox-iCAF) towards immunosuppressive extracellular matrix (ECM)-producing myofibroblasts (ECM-myCAF). In turn, ECM-myCAF polarize TREM2+ macrophages and regulatory NK cells to induce immunosuppressive EcoCellTypes. FAP+ CAF subpopulations accumulate differently depending on the invasive BC status and predict invasive recurrence of ductal carcinoma in situ (DCIS), which could help in identifying low-risk DCIS patients eligible for therapeutic de-escalation.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-07T17:55:32.991376+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000221","title":"HGG panel sequencing","description":"NGS panel sequencing of pediatric high-grade gliomas (HGG), including diffuse midline gliomas and hemispheric HGG. This is a population-based dataset from the Hospital for Sick Children (Toronto, Canada), of patients  <18 years of age at diagnosis, and diagnosed between 2000-2022. The goal of the study was to define the genetic drivers in pediatric HGG, including the rates of different genetic drivers, such as H3 and BRAF mutations, in a single-site population based cohort.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-11T12:40:35.588951+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000222","title":"Oxel Pilot Study ","description":"This pilot study will provide preliminary data regarding the role of a peripheral immunoscore (PIS) in predicting the benefit of immune checkpoint inhibition with or without chemotherapy for high risk patients with triple-negative breast cancer (TNBC) and residual disease after effective neoadjuvant chemotherapy.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-12T10:01:40.501208+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000223","title":"Single-cell transcriptomics of neuroblastoma tumors","description":"Single-cell RNA-sequencing (CITE-seq) and single-nucleus RNA-sequencing data were generated from neuroblastoma patient tumors to uncover transcriptional heterogeneity at a single-cell resolution. In addition, we used the data to validate our findings of the NBAtlas.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-06T16:06:32.260113+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000224","title":"Repeated sampling","description":"Repeated sampling experiment – sample acquisition\r\nA repeated sampling experiment was set up to specifically evaluate the effect of increasing time after death on sample quality. Selected non-tumor and large tumor tissues (with enough material available to collect for this experiment beside routine sampling) were sampled repeatedly at 1.5-hour time intervals during the autopsy.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-12T18:53:19.901397+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000225","title":"Transcriptomic characterization of the histopathological growth patterns in breast cancer liver metastases","description":"Characterizing transcriptommic profiles of the two main histopathological growth patterns in liver metastases in patients with breast cancer.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-12T18:53:21.620286+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000226","title":"Combined single-cell transcriptomics and T-cell receptor sequencing reveal heterogeneity of mycosis fungoides between and within patients and identify a CD4+ cytotoxic subtype","description":"Comprehensive analysis of the malignant cells present in the skin lesions of Mycosis fungoides, the most common subtype of cutaneous T-cell lymphoma, is complicated by the fact that malignant from reactive T cells are challenging to distinguish with certainty. To this end, combined single-cell RNA and TCR sequencing allows unambiguous identification of MF cells, thereby revealing a marked heterogeneity between and within patients with unexpected functional phenotypes. It should be further noted, that mRNA expression of established CTCL protein markers in single-cell transcriptomics to identify MF cells should be used with caution; however, our study uncovered an exciting gene expression pattern that serves as a beacon separating malignant from reactive T cells.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-02T08:19:06.053657+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000227","title":"Spatially resolved transcriptomics reveals profound subclonal heterogeneity and T cell dysfunction in extramedullary myeloma","description":"Investigating the spatial architecture and microenvironment of EMD lesions in Multiple Myeloma patients using spatial whole transcriptome sequencing (10X Visium), tomography for spatially resolved transcriptomics (TOMO-seq), and single-cell RNA sequencing (scRNAseq)","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-17T17:25:49.64025+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000228","title":"A comprehensive proteogenomic pipeline for neoantigen discovery to advance personalized cancer immunotherapy","description":" The accurate identification and prioritization of antigenic peptides is crucial for the development of personalized cancer immunotherapies. Publicly available pipelines to predict clinical neoantigens do not allow direct integration of mass spectrometry immunopeptidomics data, which can uncover antigenic peptides derived from various canonical and non-canonical sources. To address this, we present an end-to-end clinical proteogenomic pipeline, called NeoDisc, that combines state-of-the-art publicly available and in-house software for immunopeptidomics, genomics and transcriptomics with in-silico tools for the identification, prediction, and prioritization of tumor-specific and immunogenic antigens from multiple sources, including neoantigens, viral antigens and high-confidence tumor-specific antigens.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-14T12:10:13.411398+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000229","title":"Transcriptional profiling and clonality analysis of peripheral blood B cells and small intestinal plasma cells in celiac disease","description":"Single-cell RNA-seq and BCR sequencing and/or inference of sorted IgA+ peripheral blood B-lineage cells and small intestinal plasma cells of untreated celiac disease patients.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-18T12:05:29.531216+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000230","title":"Carboxylesterase 1 mediates a distinctive metabolic profile of dendritic cells to attain an inflammatory phenotype","description":"The metabolic profile of dendritic cells (DCs) shapes their phenotype and functions. Carboxylestrase 1 (CES1) enzyme is highly expressed in mononuclear myeloid cells however its exact role in DCs is elusive. We used a CES1 inhibitor (WWL113) and genetic overexpression to explore the role of CES1 in DCs differentiation in inflammatory models. \r\nCES1 expression was analyzed during CD14+ monocytes differentiation to DCs (MoDCs) using quantitative PCR. CES1 Inhibitor (WWL113) was applied during MoDCs differentiation. Surface markers, secreted cytokines, lactic acid production, phagocytic and T cell polarization capacity were analyzed. Transcriptomic and metabolic profile were assessed with RNA-sequencing and mass spectrometry. Cellular respiration was assessed with seahorse respirometry. Transgenic mice were used to assess CES1 overexpression in DCs in inflammatory models.\r\nCES1 expression peaks early during MoDCs differentiation. Pharmacological inhibition of CES1 led to higher expression of CD209, CD86 and MHCII. WWL113 treated MoDCs secreted higher quantities of IL6, IL8, TNF and IL10 and demonstrated stronger phagocytic ability and higher capacity to polarize Th17 differentiation in autologous DCs-T cells co-culture model. Transcriptomic profiling revealed enrichment of multiple inflammatory and metabolic pathways. Functional metabolic analysis shows impaired maximal mitochondrial respiration capacity, increased lactate production and decreased intracellular amino acids and TCA intermediates. Transgenic human CES1 overexpression in murine DCs generated less inflammatory phenotype and increased resistance to T cell mediated colitis. \r\nIn conclusion, CES1 inhibition directs DCs differentiation towards more inflammatory phenotype, that shows stronger phagocytic capacity and supports Th17 skewing. This is associated with disrupted mitochondrial respiration and amino acids depletion. \r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-18T12:44:38.307426+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000231","title":"Systematic immune cell dysregulation and molecular subtypes revealed by single cell RNA-seq of subjects with type 1 diabetes","description":"Type 1 diabetes mellitus (T1DM) is a prototypic endocrine autoimmune disease resulting from an immune-mediated destruction of pancreatic insulin-secreting beta-cells. A comprehensive immune cell phenotype evaluation in T1DM has not been performed thus far at the single. In this cross-sectional analysis, we generated a single-cell transcriptomic dataset of peripheral blood mononuclear cells (PBMCs) from 46 manifest T1DM (Stage 3) cases and 31 matched controls.Our study reveals a surprisingly strong systemic dimension at the level of immune cell network in T1DM, defines disease-relevant molecular subtypes and has the potential to guide non-invasive test development and patient stratification.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-18T12:59:53.306752+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000232","title":"Neversmoker lung adenocarcinoma","description":"Non-small cell lung cancer whole genome sequencing\r\n\r\nWe performed whole genome sequencing of Korean never-smoker lung adenocarcinoma patients to discover novel pathway except EGFR and ALK patients. We identified estrogen signaling as a novel enriched signaling. Lastly we validated the elevated estrogen signaling through immunohistochemistry experiment in some patients which increased signaling.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-02T12:51:30.936921+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000233","title":"Patient-Derived Follicular Lymphoma Spheroids recapitulate lymph node signaling and immune profile, uncovering galectin-9 as a novel immunotherapeutic target","description":"RNA-seq data from CD20+ sorted cells obtained from peripheral blood and lymph node Follicular Lymphoma patients. These samples were unstimulated after thawing and additionally, peripheral blood samples were stimulated during 7 days in culture as described in Dobaño-López C et. al.)","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-20T14:27:08.587132+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000234","title":"cell-Free DNA Genomic Profiling and its Clinical Implementation in Advanced Prostate Cancer","description":"Sixty-eight patients with advanced prostate cancer in castration-resistant or castration-sensitive settings undergoing treatment at the University Hospital Basel or the St. Claraspital Basel (Switzerland) were selected for targeted parallel sequencing analysis on liquid biopsy (plasma cfDNA) and matched formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[38201475],"external_links":null,"is_released":true,"released_date":"2024-04-02T11:43:39.090332+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000235","title":"BAP1 study","description":"Background: Mutations in BAP1 have been identified in many aggressive cancers. Current therapeutic strategies for BAP1-deficient tumors are not effective.\r\nGoal: Discover novel strategies for BAP1-deficient tumors.\r\nDetails: In our study, we identified a potential therapeutic strategy for BAP1-deficient cancers. We used multi-omics approaches to understand the underlying mechanisms behind why the discovered potential therapeutic strategy is effective. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-14T12:51:42.91799+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000236","title":"Panel sequencing of endocrine-resistant breast cancer","description":"Patients with endocrine-resistant breast cancer in Stockholm Sweden. DNA obtained from patients primary and relapse tumors, and tumor-free lymph nodes used as germline control. DNA was extracted from formalin-fixed paraffin-embedded tissue and sequenced by 370-gene panel-based sequencing with Kapa HyperPlus library preparation and Twist Bioscience hybrid capture. Custom bait sets (panels) from Twist Bioscience. Paired end 2x150 bp using NovaSeq X. The data is presented as fastq-files.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-21T17:51:31.345288+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000237","title":"Somatic mutations of non-malignant T cells","description":"Somatic mutations in T cells can cause cancer but also have implications for immunological diseases and cell therapies. The mutation spectrum in non-malignant T cells is unclear. Here, we examined somatic mutations in CD4+ and CD8+ T cells from 90 patients with hematological and immunological disorders and used T cell receptor (TCR) and single-cell sequencing to link mutations with T cell expansions and phenotypes. CD8+ cells had higher mutation burden than CD4+ cells. Notably, the biggest variant allele frequency (VAF) of non-synonymous variants was higher than synonymous variants in CD8+ T cells, indicating non-random occurrence. The non-synonymous VAF in CD8+ T cells strongly correlated with the TCR frequency, but not age. We identified mutations in pathways essential for T cell function and often affected in lymphoid neoplasia. Single-cell sequencing revealed cytotoxic Temra phenotypes of mutated T cells. Our findings suggest that somatic mutations contribute to CD8+ T cell expansions without malignant transformation.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-02T11:51:57.357372+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000238","title":"Genomic profiles associated with response to immunotherapy in adolescent and young adult patients with melanoma","description":"The patterns of immune infiltration and treatment responses are unclear due to genomic and clinicopathological differences in AYA patients compared to those of older patients, and these patterns and differences may contribute to the lack of response to immunotherapy. This study fills the research gaps in understanding the molecular profiles of AYA melanoma and the key immunosuppressive signalling pathways contributing to tumour growth and resistance to immunotherapy","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[38589406],"external_links":null,"is_released":true,"released_date":"2024-03-21T10:41:16.834344+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000239","title":"Targeted re-sequencing of multi-region sampled tumors in PDAC","description":"Multi-region tumor samples were cut from frozen sections or FFPEs and reviewed from microdissection and H&E staining in order to select ones with high cellularity. DNA extraction was done using DNeasy Blood & Tissue Kits for frozen samples following the manufacturer’s guideline. Extracted DNAs were processed on an Illumina HiSeq 2500 in a paired end mode (100x100) using a custom targeted panel based on the list of all unique somatic mutations from the original WES data by the Integrated Genomics Operation (IGO) at Memorial Sloan Kettering Cancer Center (New York, NY).","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-07T12:50:53.745848+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000240","title":"MEMORI WES bams ","description":"This project stores bam files from deep whole exome sequencing from oesophageal adenocarcinoma at different timepoints during neoadjuvant treatment (prior, during, post treatment), which were used to analyse evolutionary and phenotype dynamics in oesophageal adenocarcinoma during neoadjuvant treatment. \r\n\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-26T17:27:05.456192+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000241","title":"B Cell Receptor Study From Early Breast Cancer Tumour Samples","description":"B and T cells are key components of the adaptive immune system and play an important role in anti-cancer immunity. In this study, we performed an integrative analysis of the B cell and T cell repertoires across 25 serial breast tumour biopsies from 10 patients during neoadjuvant therapy.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-22T16:59:44.35866+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000242","title":"3' mRNA- sequencing bams","description":"This project stores bam files from 3'RNA-seq from oesophageal adenocarcinoma at different timepoints during neoadjuvant treatment (prior, during, post treatment), which were used to analyse evolutionary and phenotype dynamics in oesophageal adenocarcinoma. Samples were collected within the clinical MEMORI trial. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-26T17:27:07.227027+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000243","title":"Whole Genome Sequencing of HER2-Positive Metastatic Extramammary Paget’s Disease: A Case Report","description":"Extramammary Paget’s disease (EMPD) is a rare cancer that occurs within the epithelium of the skin. Whole genome sequencing of the tumor and matched blood was performed. Whole genome sequencing revealed the underlying copy number variation landscape in HER2-positive metastatic EMPD. The presence of alternative signalling pathways and genetic variants suggests potential interactions with HER2 signalling, which possibly contributed to the HER2 overexpression and observed response to HER2-directed therapy combined with other agents in a comprehensive treatment regimen.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-03T14:45:18.553736+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000244","title":"Spatiotemporal immune atlas of the first clinical-grade gene-edited pig-to-human kidney xenotransplant","description":"Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. We transplanted a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and studied the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells were uncommon in the porcine kidney cortex early after xenotransplantation and consisted of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages expressed genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft was detected. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression is sufficient to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation.","abstract":null,"study_type":"RNASeq","pubmed_ids":[36711785],"external_links":null,"is_released":true,"released_date":"2024-03-22T17:38:40.233304+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000245","title":"Sensitive circulating tumor DNA based residual disease detection in epithelial ovarian cancer","description":"In this study we implemented a circulating tumor DNA (ctDNA) based blood test for more accurate post-operative surveillance of this disease. We analyzed 264 plasma samples collected between June 2016 and September 2021 from 63 epithelial ovarian cancer patients using tumor-guided plasma cell-free DNA analysis to detect residual disease after treatment. Assay specificity was verified using cross-patient analysis of 1195 control samples.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-02T12:37:43.531203+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000246","title":"RNA sequencing of Non-Small Cell Lung Cancer and adjacent normal tissue","description":"RNA sequencing was performed on 108 NSCLC tumor samples and their paired adjacent normal tissues (n=21) to identify associations with clinical and immune characteristics.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-21T11:17:52.175429+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000247","title":"INTEGRATIVE MOLECULAR ANALYSIS OF SKIN TUMORS FROM CYLD CUTANEOUS SYNDROME PATIENTS","description":"CYLD cutaneous syndrome (CCS) is a rare autosomal dominant disorder characterized by germline CYLD mutations and by multiple benign skin tumors dependent on NF-kB pathway. We assembled a large cohort of CCS rare skin tumors that was profiled with whole exome or genome sequencing, RNA sequencing and methylation arrays to better understand genetic mechanisms of CCS tumorogenesis.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-02T11:53:36.411497+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000248","title":"RNA sequencing of serial samples from patients enrolled in the NA-PHER2 trial","description":"Improved outcomes in HER2+ breast cancer have resulted from chemotherapy and anti-HER2 therapies. However, HER2+ER+ cancers exhibit lower response rates. The NA-PHER2 trial investigated chemo-free preoperative HER2 and CDK4/6 blockade with or without endocrine therapy in HER2+ER+ breast cancer. Through RNA sequencing and tumour infiltrating lymphocytes (TIL) assessment in serial biopsies we identified predictive biomarkers of pCR, Day 14 Ki67 response, and unveiled treatment-induced molecular changes. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-14T12:49:08.937292+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000249","title":"Single nuclei RNAseq data from HGSOC primary tumour samples","description":"As described in Burdett et al, snRNAseq was performed on primary HGSOC tumour samples that had previously undergone bulk WGS and RNAseq as described in Patch et al 2015 Nature.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-03T14:36:41.651943+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000250","title":"Oligodendrogliomas originate in early childhood, accelerate growth through clonal evolution and have predictable recurrence times (H043)","description":"Oligodendrogliomas are slowly growing central-nervous-system tumors that inevitably progress. Here, we elucidate how genetic evolution shapes growth and recurrence of these tumors by combining deep whole-genome sequencing of primary-relapse pairs with molecular clock analysis and mathematical inference. We find that oligodendrogliomas originate in childhood and evolve over decades with increasing growth rate. Growth acceleration is linked to subclonal selection, with TERT promoter mutations having strong impact. Weaker selection was associated with mutations in CIC, NOTCH1, ZBTB20 or ATM, or was not associated with known drivers. Relapse tumors showed ongoing subclonal selection, with or without known drivers. The time to recurrence of individual resected oligodendrogliomas was determined jointly by the growth rate of the primary tumor and the extent of surgical resection. Thus, our findings indicate that the dynamics of tumor evolution and recurrence can be predicted, on a personalized basis, using genome sequencing of the primary tumor.  ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000251","title":"Anti-TIGIT antibody tiragolumab improves PD-L1 blockade via myeloid and Treg cells","description":"Tiragolumab, an anti-TIGIT antibody with an active IgG1/kappa Fc, demonstrated improved outcomes in the phase 2 CITYSCAPE trial (NCT03563716) when combined with atezolizumab (anti-PD-L1) versus atezolizumab alone1. However, there remains little consensus on the mechanism(s) of response with this combination2. We found that high baseline intratumoral macrophages and Tregs were associated with better outcomes in patients treated with atezolizumab plus tiragolumab but not with atezolizumab alone. Serum sample analysis revealed that macrophage activation was associated with clinical benefit in patients receiving the combination treatment. In mouse tumor models, tiragolumab surrogate antibodies inflamed tumor-associated macrophages, monocytes, and dendritic cells through Fc gamma receptors (FcɣR), in turn driving anti-tumor CD8+ T cells from an exhausted effector-like state to a more memory-like one. These results uncover a mechanism of action by which TIGIT checkpoint inhibitors can remodel immunosuppressive tumor microenvironments, and suggest that FcɣR engagement is an important consideration in anti-TIGIT antibody development.\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-26T17:32:40.492064+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000252","title":"A neoadjuvant, phase II trial demonstrates efficacy and tolerability of Talimogene laherparepvec in cutaneous basal cell carcinoma (NeoBCC trial)","description":"We present a single arm, phase II neoadjuvant trial with the oncolytic virus Talimogene laherparepvec (T-VEC) in 18 patients with difficult-to-resect basal cell carcinomas. Six cycles of T-VEC were applied intralesionally. The primary endpoint of the study, defined as the proportion of the patients, who after six cycles of T-VEC (13 weeks) at the time point of surgery, become resectable with primary wound closure without the need for plastic reconstructive surgery like skin flaps or skin grafts, was achieved (9/18 patients; 50.0%). Secondary endpoints also included the relapse free survival rate (100%), overall survival (100%) and biological read outs in the tumor samples. T-VEC led to a significant increase of cytotoxic T cells, B cells and myeloid cells, and a decrease of Tregs within the tumor microenvironment. We observed a potent induction of antitumoral and antiviral T cell clones, as well as a strong humoral immune response. The objective response rate was 55.6% and the complete pathological response rate was 33.3%. Only mild adverse events occurred. Together, neoadjuvant T-VEC represents a viable treatment option for patients with difficult-to-resect BCCs (EudraCT Number 2018-002165-19).","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-03-25T16:34:46.285272+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000253","title":"RREB1 haploinsufficiency protects against type 2 diabetes by improving insulin sensitivity in mouse and human adipocytes","description":"There are multiple independent genetic signals at the ras-responsive element binding protein 1 (RREB1) locus associated with type 2 diabetes risk, fasting glucose, ectopic fat, height, and bone mineral density. Loss of RREB1 in pancreatic beta cells reduces insulin content and impairs islet cell development and function.  However, RREB1 is a widely expressed transcription factor, and at least one signal is due to a coding variant affecting all tissues, yet the metabolic impact of global RREB1 loss in vivo remains unknown. Here, we show that male global heterozygous knockout (Rreb1HET) mice have reduced body weight and fat mass due to an increased proportion of small adipocytes. When challenged with a high-fat diet, male Rreb1HET mice gain less weight and have improved insulin sensitivity. Both male and female Rreb1HET mice have evidence of mild hepatic dysfunction, and significant reductions in food intake. Mouse and human precursor cells lacking RREB1 have decreased adipogenic gene expression and activated transcription of genes involved in osteoblast differentiation, which was associated with Rreb1HET mice having increased bone mineral density in vivo. Finally, human carriers of RREB1 T2D protective alleles have smaller adipocytes. Together, our results are consistent with RREB1 loss-of-function reducing diabetes risk. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000254","title":"Mitochondrial DNA mosaicism in human somatic cells","description":"Genomic alterations accumulate in the somatic cells throughout an individual’s lifetime. Recent sequencing studies have documented widespread mutations in the nuclear genome and the frequent clonal competition of normal cells carrying mutations. However, the landscape of mitochondrial DNA (mtDNA) heteroplasmy in normal human tissues is poorly understood. This study investigated the whole genome sequences (WGSs) of 2,096 clones established from non-neoplastic healthy single cells obtained from 31 donors. In addition, we analyzed 31 WGSs of neoplastic cells, including 12 clones established from adenomatous polyps from one individual with MUTYH-associated polyposis and 19 matched colorectal carcinomas from individuals who donated normal colorectal clones.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-02T10:50:33.907089+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000255","title":"Whole genome sequencing of Angioimmunoblastic lymphoma","description":"Angioimmunoblastic T cell lymphoma (AITL) is the most common T cell lymphoma among the uncommon family of peripheral T cell lymphoma (PTCL). Till this date, there has been no study of AITL using whole-genome sequencing technology (WGS). Hence, we use WGS data of 25 AITL tumors and their matched normal to unravel the genome-wide somatic mutational landscape. In addition, we also compare them to PTCL-NOS (not otherwise specified) and highlight genomic mutational unique to the tumoriogenesis of AITL. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000256","title":"Perturb-seq on CRC","description":"Systematic, genome-wide Investigation of enhancer regions in colorectal cancer. We used scRNA-seq with CRISPRi/dCas9 inhibition of 12,117 regions.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-08T15:41:25.578949+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000257","title":"A fast, affordable and minimally-invasive diagnostic test for Cancer of Unknown Primary (CUP) using DNA methylation profiling","description":"CUP diagnosis on FFPE tissue and liquid biopsies (blood, pleural and peritoneal effusions) using cfRRBS (cell-free reduced representation bisulfite sequencing), a technique that allows for identification of the methylation profile starting from minimal amounts of highly fragmented DNA.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-22T11:45:55.075161+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000258","title":"TCRseq","description":"T cell receptor sequencing of tumor samples. Briefly, DNAse I treated tumor RNA samples were subjected to library preparation using AmpliSeq Immune Repertoire Panel (Illumina) and sequenced using NextSeq500.","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-02T11:55:20.2963+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000259","title":"Whole Exome Sequencing","description":"The objective of this study was to better understand the molecular changes occurring in tumors during development of ICB (immune checkpoint blockade) resistance. Here, we performed Whole Exome Sequencing (WES) on biopsies from a cohort of melanoma patients after progression on anti-CTLA4 or anti-PD1 monotherapy and matched normal samples. Genetic alterations of antigen presentation and interferon gamma signaling pathways were observed in approximately 25% of ICB resistant cases.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-02T11:55:22.248149+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000260","title":"Genomic gain of EBV's LMP-1 in NKTCL","description":"The study found a high recurrence of genomic gain of LMP1 locus within EBV-associated NKTCL. The pilot data set and extended dataset of 77 WGS NKTCLs found 18/77 tumoral genomes to harbour genomic gain of LMP-1 locus within the EBV viral genomes within NKTCL tumoral sequencing data. The study also found 1/10 NKTCL cell lines to be positive for LMP-1 locus gain within EBV genomes too. This dataset includes solely the confirmatory WGS data of LMP-1 gain from NKYS cell lines using Oxford Nanopore long-read sequencing technology.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[10803505,9694726],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000261","title":"Medulloblastoma WES","description":"WES for tumor and normal samples","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-02T11:57:21.487961+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000262","title":"Medulloblastoma RNAseq","description":"Medulloblastoma rnaseq","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-02T11:57:21.487961+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000263","title":"Peripheral blood DNA methylation and transcriptomics of vedolizumab and ustekinumab treatment response in patients with Crohn's disease","description":"Biological therapeutics are now widely used in Crohn’s disease (CD), with evidence of efficacy from randomised trials and real-world experience. Primary non-response is a common, poorly understood problem. We assessed blood methylation as a predictor of response to vedolizumab (VDZ, anti-a4b7 integrin) or ustekinumab (USTE, anti-IL-12/23p40). We report a two-center, prospective cohort study in which we profiled the peripheral blood DNA methylome of adult male and female CD patients. Samples were obtained prior to and during treatment with VDZ or USTE in a discovery and a validation cohort. Response to VDZ or USTE was defined based on a combination of ≥50% reduction in the endoscopic SES-CD score, corticosteroid-free clinical remission (≥3 point drop in HBI or HBI ≤4 and no systemic steroids) and/or biochemical response (C-reactive protein (CRP) and fecal calprotectin (FCP) reduction ≥50% or ≤5 mg/L and fecal calprotectin ≤250 µg/g).","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-15T15:38:33.308297+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000264","title":"Etiology of congenital thyroid dysfunction in Down Syndrome: a multi-omics investigation","description":"The goal of this study was to investigate dfiferences in the thyroid DNA methylome and transcriptome between fetuses with Down syndrome and fetuses with no genetic/developmental abnormality.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-17T15:48:04.739777+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000265","title":"Anti-tumor and Immune Stimulatory Activity of Iberdomide in Myeloma, Including Patients with Cereblon Dysregulation","description":"Study showing Iberdomide treatment leads to immune stimulation and shift to effector T cells in triple-class refractory patients and directly after IMiD therapy.  This is the first clinical evidence that Iberdomide can overcome Cereblon defects associated with IMiD resistance in late-line myeloma patients.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-10T15:08:54.434615+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000266","title":"Non-invasive prediction of immunotherapy response (NIPIT) project","description":"This project aims to find transcriptomic biomarkers for immunotherapy response prediction in several cancer types. So far, we have performed poly-A RNA-seq using whloe blood and peripheral blood mononuclear cells from 33 non-small cell lung cancer patients, collected before and after the start of immunotherapy.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-02T17:36:53.203958+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000267","title":"Circulating RNAs prior to endometrial cancer diagnosis","description":"We analyzed circulating RNA levels using small RNA sequencing, targeting RNA  in the size range 17 to 47 nucleotides, in samples collected prior to  endometrial cancer diagnosis compared to cancer-free controls. The analysis included 316 cases with samples collected 1-11 years prior to diagnosis , and 316 matched controls, both from the Janus Serum Bank Cohort in Norway. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-16T14:40:29.408483+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000268","title":"PRADO trial - Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab plus nivolumab in stage III melanoma","description":"The PRADO trial tested a personalized response-directed treatment approach based on the pathologic response after neoadjuvant ipilimumab plus nivolumab in stage III melanoma patients. In patients achieving a major pathologic response, in their index lymph node (the largest lymph node metastasis at baseline), therapeutic lymph node dissection (TLND) and adjuvant therapy were omitted. Patients with partial response underwent TLND only, whereas patients with pathologic non-response underwent TLND and adjuvant systemic therapy ± synchronous radiotherapy.\r\n","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-08T10:44:20.246873+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000269","title":"Single cell and spatial transcriptomics of adult human adrenal glands","description":"Adrenal glands are endocrine organs secreting a variety of hormones, known to undergo tissue remodelling through constant cellular turnover. Here we employed single cell and spatial transcriptomics to investigate thoroughly adult human adrenals from 14 individuals with a focus on adrenocortical cell types and cell states. By including both male and female tissue donors of various ages, we extended the study to sexual dimorphic features of the adult gland.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-15T10:14:14.407206+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000270","title":"Whole exome sequencing of preneoplasia lung adenocarcinoma","description":"Multi-region exome sequencing of 271 pulmonary nodules and matched adjacent lung tissue including lung preneoplasia atypical adenomatous hyperplasia (AAH, N=49), adenocarcinoma in situ (AIS, N=42), minimally invasive adenocarcinoma (MIA, N=37), invasive lung adenocarcinoma (ADC, N=57) and adjacent lung tissues (Normal, N=88).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-02T12:54:10.811207+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000271","title":"RNAseq of preneoplasia lung adenocarcinoma","description":"RNA sequencing of 168 pulmonary samples including lung preneoplasia atypical adenomatous hyperplasia (AAH, N=38), adenocarcinoma in situ (AIS, N=22), minimally invasive adenocarcinoma (MIA, N=19) and invasive lung adenocarcinoma (ADC, N=38) and adjacent lung tissues (Normal, N=62).","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-02T12:54:07.04642+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000272","title":"Whole genome sequencing of preneoplasia lung adenocarcinoma","description":"Whole genome sequencing of 42 pulmonary samples including lung preneoplasia atypical adenomatous hyperplasia (AAH, N=5), adenocarcinoma in situ (AIS, N=7), minimally invasive adenocarcinoma (MIA, N=6) and invasive lung adenocarcinoma (ADC, N=8) and adjacent lung tissues (Normal, N=16).","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-02T12:54:08.933965+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000273","title":"SARS-CoV-2 induced alterations of the upper airway DNA methylome exert long-term impacts on ciliary genes involved in ciliary function","description":"Enzymatic DNA methylome (n=33) and single-cell RNA (n=24) sequencing were performed in nasal cells of COVID-19 patients and controls. In addition, we re-sampled a subset of patients for transcriptome analyses at 3 and 12 months post-infection and followed the expression of differentially regulated genes over time.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-03T12:28:46.540296+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000274","title":"Co-occurrence of KMT2D or IGLL5 mutation with mutated-MYD88 predicts unfavorable survival in patients with chronic lymphocytic leukemia in Taiwan ","description":"Whole genome sequencing and whole exome sequencing analysis on 30 patients showed that 9 genes were more frequently mutated in this Asian cohort than in the Western cohorts. Three of them were further analyzed by targeted sequencing in another 185 CLL patients, unravelling frequencies of 29.32%, 20.9%, and 15.0% for IGLL5, MYD88, and KMT2D, respectively. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000275","title":"Tumor heterogeneity and immune-evasive microenvironment in T follicular helper cell lymphomas","description":"Single-cell analysis data for tumor and immune cells from lymph node and peripheral blood samples of 14 patients with T follicular helper cell lymphomas","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[38012392],"external_links":null,"is_released":true,"released_date":"2024-04-03T14:50:26.323425+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000276","title":"Mutation detection of T follicular helper cell lymphomas","description":"Whole-exome sequencing data for study of tumor heterogeneity and immune-evasive microenvironment in T follicular helper cell lymphomas","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[38012392],"external_links":null,"is_released":true,"released_date":"2024-04-03T14:50:28.542146+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000277","title":"Combination pembrolizumab and radiotherapy induces systemic anti-tumor immune responses in immunologically-cold non-small cell lung cancer","description":"This data set includes sequence files from whole exome sequencing and RNA sequencing from serial tissue and blood biospecimens from a phase 2 clinical trial of stereotactic body radiation therapy (SBRT) followed by pembrolizumab in metastatic non-small cell lung cancer (NSCLC; NCT02492568). ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-12T09:44:28.435374+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000278","title":"Human lymphoid-neutrophil/monocyte restriction co-ordinately activates increased proliferation despite parallel heterogeneity in transcriptional changes","description":"Recent studies indicate the human lympho-myeloid restriction process to be a different and more heterogeneous one than historically inferred. Here we describe the development of bulk and clonal culture systems that efficiently support early B-lymphoid differentiation and their use to identify biological and molecular changes that accompany their initial restriction from subsets of CD34+ human cord blood cells with lympho-myeloid-limited potential. Analyses of the changes observed revealed the acquisition of B-lymphoid- and neutrophil/monocyte (NM)-restricted properties are accompanied by a concomitantly accelerated and lineage-shared cell cycling activity and loss of self-renewal properties. Parallel, single-cell transcriptome analysis identified reduced expression of multiple self-renewal-associated genes and an accompanying heterogeneous activation of lineage-regulatory modules during the production of B, NM and dendritic cell precursors. These results uncover a connected regulation of lineage-shared proliferation control with persistent heterogeneity in the biological and transcriptional changes in the same cells undergoing B and NM lineage restriction.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-03T14:43:12.533512+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000279","title":"Clonal heterogeneity leads to secondary resistance in a melanoma patient after adoptive cell therapy with tumor-infiltrating lymphocytes","description":"Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is effective in melanoma patients, although long-term responses seem restricted to patients with complete remissions. Many patients develop secondary resistance to TIL-ACT but involved mechanisms are unclear. Here, we describe a case of secondary resistance to TIL-ACT likely due to intratumoral heterogeneity and selection of a resistant tumor cell clone via transferred T cells. This is the first case of clonal selection of a pre-existing non-dominant tumor cell clone and demonstrates a new mechanism involved in secondary resistance to TIL-ACT and\r\ncould potentially change current clinical practice, because it advocates for T cell collection from different tumor sites and analysis of tumor heterogeneity before the treatment with TIL-ACT.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-15T11:09:10.460525+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000280","title":"TOPARP-B patient cell-free DNA WGS","description":"Sequencing files for TOPARP-B patients as described in manuscript","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-02T16:14:12.764618+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000281","title":"TOPARP-B patient cell-free DNA targeted sequencing","description":"Targeted sequencing for TOPARP-B patients as detailed in manuscript","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-02T16:14:12.764618+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000282","title":"Whole genome sequencing of peripheral t cell lymphoma - not otherwise specified","description":"Angioimmunoblastic T cell lymphoma (AITL) is the most common T cell lymphoma among the uncommon family of peripheral T cell lymphoma (PTCL). Till this date, there has been no study of AITL using whole-genome sequencing technology (WGS). Hence, we use WGS data of 25 AITL tumors and their matched normal to unravel the genome-wide somatic mutational landscape. In addition, we also compare them to 19 PTCL-NOS (not otherwise specified) and highlight genomic mutational unique to the tumoriogenesis of AITL. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000283","title":"Single-nuclei histone modification profiling of the adult human central nervous system unveils epigenetic memory of developmental programs","description":"Here, we profile the adult human CNS from distinct regions, sex and ages, for chromatin accessibility at the single-nuclei level. Tissue was collected from 20 different donors (10 male, 10 female) within the ages of 34 to 74 years old. Each donor donated fresh frozen white matter from the following three tissue regions: primary motor cortex (Brodmann area 4, BA4), arbor vitae cerebelli (CB) and fasciculi cuneatus and gracilis from and cervical spinal cord (CSC). Tissue was processed semi-randomly, ensuring that each batch of experiments had a representation of both sexes and all three tissue regions. Completed libraries were again randomly multiplexed during sequencing to minimize batch effects. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-14T15:59:19.69364+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000284","title":"Heterogeneity and evolution of DNA mutation rates in microsatellite-stable colorectal cancer","description":"A mutation accumulation experiment in colorectal cancer (CRC) derived tumoroids, aimed at measuring the spontaneous rates of accumulation of new single-nucleotide sequence variations in seven microsatellite stable CRCs and one microsatellite unstable CRC. Mutations accumulated over six+six months were identified via whole genome sequencing of clonal tumoroids.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-05T09:42:10.064949+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000285","title":"multiome (RNA+ATAC) characterisation of MTLE+HS samples","description":"To dissect the molecular landscape from drug-resistant mesial temporal lobe epilepsy (MTLE+HS), we characterized 16 hippocampal sclerosis type I patients exhibiting similar ages, sex, and disease duration. We used 10X multiome (RNA-seq and ATAC-seq) to recover and analyse 4,000 nuclei per sample. After rigorous quality control measures, the dataset retained over 59,000 cells.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000286","title":"Comprehensive peripheral blood immunoprofiling reveals five immunotypes with immunotherapy response characteristics in cancer patients","description":"The lack of comprehensive diagnostics and consensus analytical models for evaluating the status of a patient’s immune system has hindered a wider adoption of immunoprofiling for treatment monitoring and response prediction in cancer patients. To address this unmet need, we developed an immunoprofiling platform that uses multiparameter flow cytometry and RNA-seq to characterize immune cell heterogeneity in the\r\nperipheral blood of healthy donors and patients with advanced cancers. Using\r\nunsupervised clustering, we identified five immunotypes with unique distributions of\r\ndifferent cell types, and gene expression profiles.","abstract":null,"study_type":"RNASeq","pubmed_ids":[34019806,35944503],"external_links":null,"is_released":true,"released_date":"2024-06-05T16:39:42.756727+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000287","title":"Molecular underpinnings of dedifferentiation and aggressiveness in chromophobe renal cell carcinoma","description":"This study expands our understanding of aggressive chromophobe renal cell carcinoma (ChRCC), provides insight into molecular mechanisms of tumor progression, and informs pathologic classification and diagnostics. Tumor and adjacent normal samples were collected from 11 patients treated in affiliated hospitals of the University of Texas Southwestern Medical Center (UTSW), including Parkland Hospital. Seven of the eleven patients consented to depositing their genomic data to public repository.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-21T13:57:27.67443+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000288","title":"WGS of cord blood hematopoietic stem and progenitor cells","description":"In this study, the mutational effects of prenatal chemotherapy exposure on cord blood hematopoietic stem and progenitor cells was investigated in cord blood samples taken from 10 healthy pregnant women, 4 pregnant cancer patients receiving no systemic anti-cancer treatment during pregnancy and 12 pregnant cancer patients receiving chemotherapy during pregnancy. Sequencing was performed on Illumina platforms.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-22T16:29:20.497154+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000289","title":"Whole exome RNA sequencing of FFPE material from 49 pediatric BCP-LBL patients.","description":"This study contain the results of whole exome-targeted transcriptome analyses of FFPE material from 49 pediatric B-cell precursor lymphoblastic lymphoma patients. Data are provided as Fastq files. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-09T16:13:52.470118+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000290","title":"Whole exome sequencing of FFPE material from 41 pediatric BCP-LBL patients.","description":"This study contain the results of whole exome sequencing analyses of FFPE material from 41 pediatric B-cell precursor lymphoblastic lymphoma patients. Samples were sequenced with a target coverage of 200x. Data are provided as Fastq files. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-09T16:13:50.396082+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000291","title":"Multiregion exome sequencing of ovarian immature teratomas","description":"Tumor tissue from each of the indicated ovarian and disseminated GCT components was selectively punched from formalin-fixed, paraffin-embedded blocks. Genomic DNA was extracted from these tumor and matched normal tissue samples, with a total of 500 ng of genomic DNA used as input for capture employing the xGen Exome Research Panel.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-10T11:16:16.970689+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000292","title":"Multiple Myeloma GWAS Meta-analysis","description":"Meta-analysis of Multiple Myeloma genome-wide association study datasets. Included are meta-analyses with and without the UK Biobank dataset.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-22T17:14:37.467386+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000293","title":"scRNA-seq of CD4+ T cells from blood, lymph nodes and tumors of NSCLC patients","description":"This study explore the CD4+ T cells diversity in paired blood, lymph nodes and tumors of 5 different NSCLC patients. After FACS-sorted of Tregs (DAPI- CD45+ CD4+ CD25hi CD127lo) and Tconvs (DAPI- CD45+ CD4+CD25lo CD127lo/hi), cells were mixed in equal proportion (fifty/fifty ratio) and processed with 10X Chromium (10X Genomics) gene expression kit (3 bloods, 2 lymph nodes and 2 tumors) or immunoprofiling kit (2 bloods, 4 lymph nodes and 3 tumors) and sequenced using Illumina platforms.\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-15T13:37:36.913349+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000294","title":"scATAC-seq of CD4+ T cells from blood, lymph nodes and tumors of NSCLC patients","description":"This study explore the CD4+ T cells diversity in paired blood, lymph nodes and tumors of 2 different NSCLC patients. After FACS-sorted of Tregs (DAPI- CD45+ CD4+ CD25hi CD127lo) and Tconvs (DAPI- CD45+ CD4+CD25lo CD127lo/hi), cells were mixed in equal proportion (fifty/fifty ratio) and procesed with 10X Chromium (10X Genomics) scATAC kit and sequenced using Illumina platforms.\r\n","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-15T13:37:36.913349+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000295","title":"WHOLE GENOME SEQUENCING OF CLEAR CELL RENAL CELL CARCINOMA IN VHL PATIENT","description":"This submission contains Whole Genome Sequencing data of six ccRCCs, four cysts and one blood DNA sample of a VHL patient. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-09T12:44:10.177062+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000296","title":"Ancient genomes reveal insights into ritual life at Chichén Itzá","description":"To better understand the origin and biological relationships of the sacrificed children from Chichén Itzá to each other and to present-day inhabitants of the region, here we used a combined bioarchaeological and genomics approach to investigate 64 subadults interred within a chultún near the Sacred Cenote and compare them to 68 present-day Maya inhabitants of the nearby town of Tixcacaltuyub, as well as to other available ancient and contemporary genetic data from the region. The community of Tixcacaltuyub has been collaborating with our research team for many years, and their perspectives informed the development of this project.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-23T12:43:01.171071+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000297","title":"Homopolymer switches mediate adaptive mutability in mismatch repair-deficient colorectal cancer","description":"Mismatch repair (MMR) deficient cancer evolves through the continuous erosion of coding homopolymers in target genes. Curiously, the MMR genes MSH6 and MSH3 also contain coding homopolymers and these are frequent mutational targets in MMR-deficient cancers. The impact of incremental MMR mutations on MMR-deficient colorectal cancer evolution is unknown. We show that microsatellite instability modulates DNA repair by toggling hypermutable mononucleotide homopolymer runs in MSH6 and MSH3 through stochastic frameshift switching. Spontaneous mutation and reversion modulates subclonal mutation rate, mutation bias, and clonal HLA and neoantigen diversity. Patient-derived organoids corroborate these observations and show that in the absence of immune selection MMR homopolymer sequences drift back into reading frame, suggesting a fitness cost of elevated mutation rates. Combined experimental and simulation studies demonstrate that subclonal immune selection favours incremental MMR mutations. Overall, our data demonstrate that MMR-deficient colorectal cancers fuel intratumour heterogeneity by adapting subclonal mutation rate and diversity to immune selection.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-23T10:43:03.450692+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000298","title":"A CCG expansion in ABCD3 causes oculopharyngodistal myopathy in individuals of European ancestry","description":"In this study we describe the identification of CCG expansions in ABCD3 in affected individuals across eight unrelated OPDM families of European ancestry. In two large Australian OPDM families, using a combination of linkage studies, short-read WGS and targeted ONT sequencing, we identified CCG expansions in the 5’UTR of ABCD3. Independently, the ABCD3 CCG expansion was identified through the 100,000 Genomics England Genome Project in three individuals from two unrelated UK families diagnosed with OPDM.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-17T12:05:44.737731+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000299","title":"Whole-genome variant calling of individuals from the study of allergic diseases in the Canary Islands","description":"Research study of genetic susceptibility and analyses of polygenic risk scores in allergic diseases. The historic influences in the Canary Islanders have resulted in an admixture of European, North Africans and Sub-saharan African genetic ancestries. Genetic risks linked to any of these ancestries could underlie disease peculiarities in the current inhabitants. To leverage genectic ancestry to identify and assess genetic risks in allergic diseases in the Canary Islands, we combine different genomic technologies in case-control studies and reference samples from the three parental populations to characterize and identify genetic risks factors and the intersection with ancestry.\r\n","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-17T12:03:26.594927+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000300","title":"Molecular Evoluation of Classic Hodkin Lymphoma (RNA)","description":"Exome sequencing to accompany the whole genome sequencing in EGA Study EGAS00001006884\r\n","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000301","title":"Single nucleus and bulk transcriptomics in prefrontal cortex of individuals with alpha synucleinopathies","description":"We explore cell-specific changes in gene expression across different α-synucleinopathies. We perform single nucleus RNA sequencing using 10X Genomics, and bulk RNA sequencing from the prefrontal cortex of individuals with alpha synucleinopathies - Parkinson's Disese (PD), monogenic LRRK2 PD, and multiple system atrophy (MSA), together with neurologically healthy controls.\r\n\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-09T13:16:02.406216+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000302","title":"Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation","description":"Background: Glioblastoma (GBM) harbors a highly immunosuppressive tumor microenvironment (TME) which influences glioma growth. Major efforts have been undertaken to describe the TME on a single-cell level. However, human data on regional differences within the TME remain scarce. \r\nGoals: we performed single-cell RNA sequencing (scRNAseq) on paired biopsies from the tumor center, peripheral infiltration zone and blood of five patients with primary GBM\r\nDetails: This EGA study includes raw data sequencing files for the scRNA-seq samples. The processed data (output from Alevin, UMI count matrix and cell metadata) are available from GEO https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE197543","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[38127790],"external_links":null,"is_released":true,"released_date":"2024-04-17T12:08:59.776825+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000303","title":"Deciphering novel TCF4-driven mechanisms underlying a common triplet repeat expansion-mediated disease","description":"short and long read data generated from cultured corneal endothelial cells (CECs) of unaffected controls, expansion positive Fuchs Endothelial Corneal Dystrophy (FECD) and expansion negative FECD individuals.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-26T16:28:51.329674+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000304","title":"Bone marrow breakout lesions act as key sites for tumor-immune cell diversification and exhaustion in multiple myeloma","description":"Multiple myeloma is a disease characterized by the expansion of cancerous plasma cells in the bone marrow. The bone marrow microenvironment plays a pivotal role in supporting myeloma growth and modulating tumor immunity. As the disease progresses, myeloma cells may become independent of the bone marrow environment, leading to extramedullary disease associated with poor prognosis. However, the early processes associated with bone marrow independence and its implications for disease and immune control remain poorly understood. Here, we employed comprehensive single-cell and spatial mapping to identify the disruption of the cortical bone and subsequent expansion of myeloma cells in breakout lesions as a key event in multiple myeloma pathogenesis and tumor immunity. Breakout lesions harbor an adapted niche and a unique immune microenvironment conferred by sustained immune-tumor interactions. In particular, tumor-reactive T cells with a highly exhausted phenotype, alongside unique NK cell and macrophage subtypes, specifically expanded in breakout lesions. Spatially-resolved genomic, transcriptomic and cellular analyses uncovered extensive intra-lesion heterogeneity, suggesting a divergent co-evolution of genomic variation and locally confined T cell responses in distinct subregions. Ultra-high plex imaging revealed that tumor-reactive T cells, together with other immune-regulatory cells and dendritic cells, co-expand and exhaust upon sustained tumor interactions in locally confined immune islands. In contrast, immune-regulatory macrophage and NK cell subsets operate spatially separated within myeloma cell deserts. Jointly, our analyses uncover bone marrow breakout lesions as a hotspot for tumor-immune cell interactions, diversification and exhaustion, representing a key event in myeloma pathogenesis with significant therapeutic implications.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[39919199],"external_links":null,"is_released":true,"released_date":"2025-02-21T12:13:15.490051+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000305","title":"resistance to FGFR inhibitor in FGR2 cancers from DNA sequencing","description":"WES from FGR2 resistant patient tumors","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-22T17:21:56.639274+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000306","title":"resistance to FGFR inhibitor from RNA sequencing","description":"WTS performed on tissues from resistant patients","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-22T17:21:56.639274+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000307","title":"Decoding Human Endogenous Retrovirus Expression in Liver Metastatic Colorectal Cancers: Implications for Diagnosis and Prognosis","description":"The association between Human Endogenous RetroVirus (HERV) expression and cancer can be considered to both reflect the epigenetic deregulation of cancer and facilitate oncogenesis through its promoter/enhancer action on genes. More than 50% of colorectal cancers develop liver metastases and HERV has never been studied in this setting.\r\nWe collected 400 RNAseq samples from more than 200 patients with primary and liver metastases from published and unpublished databases. We corroborated our findings with tandem mass spectrometry from primary colorectal cancer and single-cell RNAseq from liver metastatic colorectal cancer (lmCRC).\r\nWe identified global stability in HERV expression between liver metastases and primary colorectal cancers, suggesting an early oncogenic footprint. Therefore, we proposed a list of seventeen HERV loci for lmCRC characterization with ERV-derived peptides but no expression in normal tissues. Among them, we discovered six prognostic markers after surgical resection of lmCRC. Four of them, HERVH_Xp22.32a, HERVH_20p11.23b, HERVH_13q33.3, HERVH_13q31.3, showed poor prognostic value when expressed (log-rank p-value 0.028, 0.0083, 9e-4, 0.05, respectively). HERVH_Xp22.2c (log-rank p-value 0.032) and HERVH_8q21.3b (only in multivariate models) were associated with better prognosis when expressed. These markers showed a cumulative effect on survival when expressed. Some HERVs were associated with decreased cytotoxic immune cells and most of them correlated with cell cycle pathways.\r\nOur findings provide new insights into lmCRC classification and suggest novel prognostic biomarkers and potential therapeutic targets.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-07T13:30:47.083681+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000308","title":"CSF and PBMC scRNAseq RRMS patients at diagnostic n=5","description":"To get insights about immune cells infiltrating cells the CSF of RRMS patients (n=5), we proceed to 10X scRNAseq of paired CSF and blood circulating cells (about 20000 cells each)  sampled at diagnostic.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-07T15:22:23.986952+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000309","title":"Platinum-based chemotherapy induces opposing effects on immunotherapy response-related spatial and stromal biomarkers in the bladder cancer microenvironment","description":"The goal of the current project was to investigate the modulation of the tumor-immune microenvironment (TME) by neo-adjuvant platinum-based chemotherapy in muscle-invasive bladder cancer. Furthermore, we aimed to focus on how this modulation affects biomarkers of response to immune checkpoint inhibitors. Additionally, we aimed to explore the differences between MVAC and gemcitabine-containing platinum-based regimens regarding their effects on the bladder TME.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-23T09:15:19.892788+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000310","title":"Cell type mapping of inflammatory muscle diseases highlights selective myofiber vulnerability in inclusion body myositis","description":"Inclusion body myositis (IBM) is the most prevalent inflammatory muscle disease in older adults with no effective therapy available. In contrast to other inflammatory myopathies like subacute immune-mediated necrotizing myopathy (IMNM), IBM follows a chronic disease course with both inflammatory and degenerative features of pathology. Moreover, causal factors and molecular drivers of IBM progression are largely unknown. Therefore, we paired single-nucleus RNA sequencing with spatial transcriptomics from patient muscle biopsies to map cell type-specific drivers underlying IBM pathogenesis compared to IMNM muscles and non-inflammatory skeletal muscle samples. In IBM muscles, we observed a selective loss of type 2 myonuclei paralleled by increased levels of cytotoxic T and cDC1 cells. IBM myofibers were either characterized by upregulation of cell stress markers featuring GADD45A and NORAD, or protein degradation markers including RNF7 associated with p62 aggregates. GADD45A upregulation was preferentially seen in type 2A myofibers associated with severe tissue inflammation. We also noted IBM-specific upregulation of ACHE encoding acetylcholinesterase, which can be regulated by NORAD activity and result in functional denervation of myofibers. Our results provide promising insights into possible mechanisms of myofiber degeneration in IBM and suggest a selective type 2 fiber vulnerability linked to genomic stress and denervation pathways.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-02T17:54:15.681927+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000311","title":"Bulk RNA-seq of monocytes and in vitro cultured monocyte-derived macrophages of ANCA-associated vasculitis patients with active and stable disease and healthy controls","description":"To study monocyte and macrophage activation in ANCA-associtated vasculitis (AAV), we performed bulk RNA sequencing of bead-selected monocytes and in vitro cultured monocyte-derived macrophages from AAV patients and healthy controls. Overview patients included for sequencing monocytes: - AAV active disease, n=4, MPO-AAV=4 - AAV remission, n=10, PR3-AAV=5, MPO-AAV=5 - Healthy controls, n=6 Overview patients included for sequencing monocyte-derived macrophages: - AAV active, n=1, PR3-AAV=1 - AAV remission, n=3, PR3-AAV=3 - Healthy controls, n=3","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-10T14:02:28.716197+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000312","title":"Primary central nervous system lymphoma (PCNSL) biopsies show heterogeneity in gene expression profiles, genetic subtypes, and in vitro drug sensitivity to kinase inhibitors","description":"Primary central nervous system lymphoma (PCNSL) is an aggressive large B-cell lymphoma, most often of the activated B cell (ABC) subtype, but with limited tumor biology studies due to small biopsy size and lack of strict cohort definition. Here we examined the genetic heterogeneity of 29 HIV- EBV- PCNSL tumors using whole exome sequencing (WES). We compared these tumors to 5 cell lines comprised of two human PCNSL cell lines (TK and HKBML) and three systemic activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) (OCI-Ly3, TMD-8, HBL-1).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-23T11:18:52.521592+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000313","title":"TRACERx NSCLC  - whole genome sequencing for ctDNA study","description":"An ultra-sensitive and specific ctDNA assay provides novel pre-operative disease stratification in early stage lung adenocarcinoma","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-27T11:52:42.857788+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000314","title":"Tracing tumor evolution and heterogeneity of pleomorphic carcinoma of the lung","description":"Pulmonary pleomorphic carcinoma (PPC) is an aggressive and highly heterogeneous non-small-cell lung carcinoma whose underlying biology is still poorly understood. Forty-two tumor areas including 39 primary tumors and 3 metastases from 20 PPC patients were microdissected and the histologically distinct components were subjected to whole exome sequencing (WES) separately. Twenty non-tumor areas from matched PPC patients were also subjected to WES. Twist Human Core Exome + RefSeq + Mito-Panel kit (Twist Bioscience) was used for the whole exome capturing according to manufacturer’s guidelines. Paired-end 100-bp reads were generated on the Illumina NovaSeq 6000. \r\nAfter the sequencing, reads were aligned against the reference human genome GRCh38 using Burrows-Wheeler Aligner (BWA, v0.7.12)\r\n","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-21T12:31:30.908137+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000315","title":"Circulating tumor DNA dynamics reveal KRAS G12C mutation heterogeneity and response to treatment with the KRAS G12C inhibitor divarasib in solid tumors","description":"Purpose: To inform prognosis, treatment response, disease biology, and KRAS G12C mutation heterogeneity, we conducted exploratory circulating tumor DNA (ctDNA) profiling on 134 patients with solid tumors harboring a KRAS G12C mutation treated with single-agent divarasib (GDC-6036) in a phase 1 study.\r\n\r\nExperimental design: Plasma samples were collected for serial ctDNA profiling at baseline (Cycle 1 Day 1 prior to treatment) and multiple on-treatment time points (Cycle 1 Day 15 and Cycle 3 Day 1).\r\n\r\nResults: KRAS G12C ctDNA was detectable from plasma samples in 72.9% (43/59) and 92.6% (50/54) of patients with non-small cell lung cancer and colorectal cancer, respectively, the majority of whom were eligible for study participation based on a local test detecting the KRAS G12C mutation in tumor tissue. Baseline ctDNA tumor fraction was associated with tumor type, disease burden, and metastatic sites. A decline in ctDNA level was observed as early as Cycle 1 Day 15. Serial assessment showed a decline in ctDNA tumor fraction associated with response and progression-free survival. Except for a few cases of KRAS G12C sub-clonality, on-treatment changes in KRAS G12C variant allele frequency mirrored changes in the overall ctDNA tumor fraction.\r\n\r\nConclusion: Across tumor types, the KRAS G12C mutation likely represents a truncal mutation in the majority of patients. Rapid and deep decline in ctDNA tumor fraction was observed in patients responding to divarasib treatment. Early on-treatment dynamics of ctDNA were associated with patient outcomes and tumor response to divarasib treatment. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-08T10:56:02.574394+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000316","title":"Distinct patient, tumor and CAR T cell charateristics are associated with initiating versus sustaining responses to idecabtagene vicleucel in relapsed/refractory multiple myeloma","description":"This study evaluate tumor intrinsic genomic and transcriptional features associated with responses to ide-cel in the KarMMa study. Molecular multiple myeloma high risk segments were evaluated by whole genome sequencing and correlations with overall response and progression free survival (PFS) were evaluated. Two novel genomic loci, del14q and del1p, were identified that associated with PFS and transcriptional analyses of tumors with vs without these lesions were conducted.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000317","title":"Tanzania dietary intervention study 2019-2020","description":"We performed a dietary intervention study comparing western diet, traditional diet and the supplementation of fermented banana beverage in a cohort of 66 individuals (22 in each study arm)","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-11T10:54:01.616644+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000318","title":"HiDEF-seq single-molecule sequencing of single-strand mismatches and damage","description":"Our study sought to resolve, with single-molecule fidelity, the mismatches and damage events that precede DNA mutations. Using a novel single-molecule, long-read sequencing method (HiDEF-seq) we detect base substitutions when present in either one or both DNA strands. We also detect cytosine deamination, a common type of DNA damage, with single-molecule fidelity. This study profiled 134 samples from diverse tissues, including from individuals with cancer predisposition syndromes. These samples revealed single-strand mismatch and damage signatures. Since double-strand DNA mutations are only the endpoint of the mutation process, our approach enables new studies of how mutations arise in a variety of contexts, especially in cancer and aging.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-04-26T14:15:53.28304+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000319","title":"Regulatory Elements active in Insulinomas","description":"Characterization of regulatory elements active insulinomas, assessed by the presence of H3K27ac. This study also includes characterization of H3K27me3 in control pancreatic beta cells.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-01T16:53:01.984371+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000320","title":"Transcriptome of insulinomas","description":"Characterization of the transcriptome of insulinomas by RNA-seq.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-01T16:53:04.055699+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000321","title":"Whole Genome Sequencing of Insulinomas","description":"Whole Genome Sequencing of Insulinomas and paired blood controls from the same patients.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-01T16:53:07.902006+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000322","title":"Ribosome profiling shows variable sensitivity to detect open reading frames for conventional and different types of cryptic T cell antigens","description":"The aim of the study was to explore the sensitivity of ribosomal profiling to detect ORFs for cryptic antigens targeted by T cells in immune responses. Ribosomal profiling was performed for six EBV-LCLs. Detection of conventional and cryptic MiHA-encoding ORFs was compared. The data showed that open reading frames (ORFs) for conventional MiHAs as well as cryptic MiHAs in upstream ORFs were frequently detected with similar sensitivity. However, only a limited number of MiHAs in in reading frames alternative to protein-coding sequences and no ORFs derived from long non-coding RNAs were detected. In conclusion, Ribo-seq for identification of antigen-encoding ORFs is useful to screen for cryptic antigens in upstream ORFs as potential targets for immunotherapy.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-27T16:54:21.887726+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000323","title":"Transcriptome profiling of patient derived neural stem cells highlights the importance of CTNND2 and WNT signaling in early neuralization ","description":"Loss of CTNND2/δ-catenin function is implicated in neurodevelopmental disorders, including Cri-du-chat syndrome, autism spectrum disorder and attention deficit hyperactivity disorder. CTNND2, the encoded protein, is crucial for the cadherin-catenin cell adhesion complex in the brain. However, the specific impact on neurodevelopment remains unclear. To investigate, we used neuroepithelial stem cells (NESCs) derived from patient-specific induced pluripotent stem cells (iPSCs) with loss of CTNND2. In monolayer cultures, we observed abnormal neural rosette formation and failure to establish stable neural stem cells. 3D organoid cultures confirmed delayed neurogenesis and slower growth in patient-derived iPSC lines. We have built a transcriptomic catalog and observed a dysregulation of the WNT signaling pathway linked to our observed cellular phenotypes. To validate we excluded the WNT activator CHIR99021 from the media, which partially rescued the transcriptomic and morphological phenotype of the patient neural induction. This study enhances our understanding of how CTNND2 loss affects early neurogenesis and neuronal maturation in patient specific cells. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-21T12:01:56.016353+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000324","title":"Systematic dissection of tumor-normal single-cell ecosystems across a thousand tumors of 30 cancer types","description":"The complexity of the tumor microenvironment poses significant challenges in cancer therapy. Here, to comprehensively investigate the tumor-normal ecosystems, we perform an integrative analysis of 4.9 million single-cell transcriptomes from 1,070 tumor and 493 normal samples in combination with pan-cancer 137 spatial transcriptomics, 8,887 TCGA, and 1,261 checkpoint inhibitor-treated bulk tumors. We define a myriad of cell states constituting the tumor-normal ecosystems and also identify hallmark gene signatures across different cell types and organs. Our atlas characterizes distinctions between inflammatory fibroblasts marked by AKR1C1 or WNT5A in terms of cellular interactions and spatial co-localization patterns. Co-occurrence analysis reveals interferon-enriched community states including tertiary lymphoid structure (TLS) components, which exhibit differential rewiring between tumor, adjacent normal, and healthy normal tissues. The favorable response of interferon-enriched community states to immunotherapy is validated using immunotherapy-treated cancers (n=1,261) including our lung cancer cohort (n=497). Deconvolution of spatial transcriptomes discriminates TLS-enriched from non-enriched cell types among immunotherapy-favorable components. Our systematic dissection of tumor-normal ecosystems provides a deeper understanding of inter- and intra-tumoral heterogeneity.","abstract":null,"study_type":"RNASeq","pubmed_ids":[38744958],"external_links":null,"is_released":true,"released_date":"2024-04-30T13:13:41.320616+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000325","title":"Impact of allogeneic umbilical-cord derived mesenchymal stromal cells on B-cell scRNAseq in patients with systemic lupus erythematosus","description":"The impact of MSC(UC) on peripheral B cells from Systemic Lupus Erythematosus (SLE) patients was studied by 10X scRNAseq. This scRNAseq study encompassed 3 SLE patients at 3 time points: before or after (1 month, and 3 months) MSC injection in order to analyze B cell subsets and their DEG. The aim of this study was to observe the potential changes of B cell subsets after MSC(UC) injection in SLE patients.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-06T12:08:24.183824+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000326","title":"Characterization of palbociclib-adapted pleural mesothelioma cell lines by WES","description":"Palbociclib-adapted cells were generated from NCI-H2052, NCI-H2452 and NCI-H28 by culturing the cells in the presence of increasing concentrations of palbociclib (from 62.5 to 250 nM). Two different palbociclib-adapted cell lines (A1 and A2) were generated from each parental cell line. A drug washout experiment (1 month without palbociclib) was also perform to investigate the reversibility of the phenotype. Whole-exome sequencing was performed to compare each palbociclib-adapted cell line to its parental cell line and its washout condition.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000327","title":"Paired Biopsy Project: West Coast Dream Team","description":"This project aims to analyze the paired metastatic biopsy samples from patients with metastatic castration-resistant prostate cancer (mCRPC), collected before the initiation of the first-line androgen receptor signaling inhibitor (ARSI) for mCRPC and after radiographic disease progression on that ARSI, to understand the resistance mechanisms. We generated both whole genome sequencing (WGS) and RNA-seq data on these samples. A majority of these samples have been deposited in the public domain along with prior publications, and this project contains the 16 WGS samples that have not yet been deposited.  ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-09T13:27:00.719621+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000328","title":"Targeted capture, whole genome sequencing, and RNAseq to identify rearrangements in B-cell lymphomas","description":"This study contains whole genome and custom targeted capture sequencing of mature B-cell lymphomas (DLBCL, FL, BL, HGBCL-DH-BCL2, HGBCL-DH-BCL6) to identify translocation breakpoints of common oncogene rearrangements (MYC, BCL2, BCL6). It is complemented by RNAseq data where available. Complete details are available in the publication Hilton et al, 2024, Blood. \r\nCapture sequencing: 357 samples; 364 unique libraries; cram file format aligned to hg38\r\nWhole genome sequencing: 12 samples; 12 unique libraries; cram file format aligned to grch37\r\nRNAseq: 257 samples; 257 unique libraries; fastq file format\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[38701426,30348671],"external_links":null,"is_released":true,"released_date":"2024-05-16T17:31:04.009396+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000329","title":"The variable genomic landscape during osteosarcoma progression: insights from a longitudinal WGS analysis","description":"Osteosarcoma is a primary bone tumor that exhibits a complex genome characterized by gross chromosomal abnormalities. Osteosarcoma patients often develop metastatic disease, resulting in limited therapeutic options and poor survival rates. To gain knowledge on the mechanisms underlying osteosarcoma heterogeneity and metastatic process, it is important to obtain a detailed profile of the genomic alterations that accompany osteosarcoma progression. Therefore, in this study we performed WGS on multiple tissue samples from six patients with osteosarcoma, including the treatment naïve biopsy of the primary tumor, resection of the primary tumor after neoadjuvant chemotherapy, local recurrence and distant metastases. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-02T08:36:53.052784+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000330","title":"Targeted sequencing of genomic regions of interest in depression and obesity","description":"This study aimed to further explore the genetic relationship between MD and obesity taking advantage of targeted sequencing strategy. Specifically, we searched for genetic risk variants across the entire frequency spectrum in flanking genomic regions and genes previously associated with MD and obesity, assessed the contribution of those variants to the pathophysiology of comorbid MD and obesity, and provided a general overview of the cellular and molecular pathways mapped by those variants when these complex diseases co-occur.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-08T11:03:59.530818+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000331","title":"T cell repertorie analysis fom a Spanish cohort of mild and severe cases of COVID-19 recovered patients","description":"The cohort included 98 mild and 75 severe cases with a median age of 53 years. We amplified and sequenced the T Cell Receptor (TCR β) chain complementary determining region 3 (CDR3b) and performed bioinformatic analyses to assess repertoire diversity, clonality, allelic usage, and epitope affinity CDR3b clustering.  CDR3b sequences were amplified by multiplex PCR and sequenced by Illumina. The resulting raw files were processed for clonotype assembly, filtering for coding clonotypes, removal of non-TRB alleles, and downsampling.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-08T13:07:13.47865+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000332","title":"Single-cell RNA sequencing of 16 NPM1 mutated AML patients","description":"NPM1 mutated AML is the largest class in WHO classification, however several subtypes within NPM1 were already reported. Here, we sequence 16 NPM1 mutated AML samples with single-cell RNA-sequencing and multi-color flow cytometry from three major NPM1 subtypes we previously identified, totaling more than half a million cells. We show that the differences among three NPM1 subtypes are mainly driven by cell composition, and these differences are also reflected at cell surface protein level. With the re-analysis of CITE-seq data from another cohort and single cell variant calling on our data, we also report two distinct stem cell phenotypes: one with leukemic (CD34dimCD38-CD45RA+) and another with pre-leukemic (CD34+CD38-CD45RA-) origin. We believe that our data and findings provide novel insights regarding the etiology of NPM1 mutated AML. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-28T13:43:32.312703+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000333","title":"ROBUST (NCT02285062)","description":"The ROBUST clinical trial is a Phase III, randomized, double-blind, placebo-controlled study designed to compare the efficacy and safety of lenalidomide plus R-CHOP chemotherapy (R2-CHOP) versus placebo plus R-CHOP in newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL). Molecular data was collected for all patients at screening, but the only patients of the Activated B-cell (ABC) cell-of-origin subtype were eligible for study inclusion and clinical follow-up. We have performed unsupervised clustering on this cohort and identified 7 novel transcriptional subtypes of DLBCL, one of which represents a high-risk subset of patients with high MYC expression, ABC-associated biology, and low immune infiltration.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-19T12:27:23.002955+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000334","title":"Toxigenic Clostridium perfringens isolated from at-risk pediatric inflammatory bowel disease patients","description":"With the goal of studying mucosal-associated bacteria and products detrimental to inflammatory bowel disease (IBD) patients, we directly cultured bacterial communities from mucosal biopsies and examined for detrimental traits. Focusing on red blood cell lysis, a virulence trait, communities from 5 of 9 patients exhibited hemolytic activity. Clostridium perfringens was isolated from each hemolytic community, and whole-genome sequencing confirmed presence of hemolytic toxins – alpha toxin in all 5 strains, perfringolysin O (PFO) in 4 strains, alveolysin in 2 strains – and absence of enterotoxins. In vitro cytotoxicity experiments demonstrated strain supernatants were toxic to various cell types located beneath the intestinal epithelial barrier, including endothelial, neuroblasts, and neutrophils, while impact on epithelial cells was less pronounced. These findings suggest C. perfringens may be damaging particularly when intestinal barrier integrity is compromised, such as in IBD patients. Further characterization using purified toxins and genetic insertion mutants confirmed PFO toxin was sufficient for cell toxicity. C. perfringens supernatants also induced activation of neuroblast and dorsal root ganglion (DRG) neuron cells in vitro, suggesting C. perfringens in inflamed mucosal tissue may directly contribute to abdominal pain, a frequent IBD symptom. Strikingly, C. perfringens was detected in biopsies of 8 of 9 pediatric patients while not in all corresponding stool samples, and in other datasets, C. perfringens was in stool samples of IBD adults (18.7-27.1%) much more frequently versus healthy (5.1%). Our findings showcase C. perfringens may have an important pathogenic impact on IBD patients. Similar to Clostridioides difficile, routine monitoring of C. perfringens and PFO toxins in patients may be beneficial.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-16T16:57:03.523627+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000335","title":"single cell data from HPV-positive head and neck cancer patients receiving induction CTLA-4 and PD-1 immune checkpoint blockade","description":"Baseline and on-treatment tumor samples from human papillomavirus-positive oropharynx cancer patients receiving anti-CTLA-4 and anti-PD-1 immune checkpoint blockade were analyzed by single-cell RNA and TCR sequencing.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-02-12T10:42:05.157117+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000336","title":"Comparison between phenotypic-defined stage of blasts and transcriptional profile ","description":"Established a proof-of-concept methodology with potential integration into flow cytometry software for objective AML subtype classification based on blast differentiation, offering valuable prognostic insights for elderly patients.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-13T17:54:51.261379+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000337","title":"RNA-sequencing from duodenal bipsies of Celiac disease patients","description":"Total RNA was extracted from the PaxFPE biopsy specimens (n = 116)","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-20T09:25:00.740862+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000338","title":"RNA sequencing from patient-derived intestinal organoids","description":"RNA from the duodenal organoids was isolated using an RNeasy Kit (Qiagen, Hilden, Germany) following the manufacturer’s instructions. RNA purity and concentration were measured using a NanoDrop One spectrophotometer (NanoDrop Technologies, Wilmington, Delaware, USA). Preparation of the RNA library and transcriptome sequencing was conducted by Novogene Co., LTD (Cambridge, UK). Messenger RNA was purified from total RNA using polyA selection and subjected to library construction. Sequencing was performed on an Illumina platform, and 150 bp paired-end reads were generated. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-20T09:25:02.803374+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000339","title":"Single cell transcriptomic profiles of advanced melanoma patients treated with checkpoint inhibitor immunotherapy","description":"Little is known about the resistant clones within the tumour ecosystem treated with immunotherapy. This work provides a comprehensive and integrative analysis of each individual non-responding melanoma patients, including clinical features integrated with single cell analysis, which is critical to understand features of resistance in order to improve cancer patients’ outcomes.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-10T16:33:14.780798+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000340","title":"Whole-genome sequencing of primary mediastinal large B-cell lymphoma","description":"To understand the molecular pathogenesis of Primary mediastinal large B-cell lymphoma (PMBCL), we performed whole-genome sequencing of 10 PMBCLs from 8 patients including 2 relapsed tumors.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[38055913],"external_links":null,"is_released":true,"released_date":"2024-05-17T12:48:20.019931+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000341","title":"Epigenetic memory of SARS-CoV-2 mRNA vaccination in monocyte-derived macrophages","description":"Immune memory is key to effective antimicrobial responses, but the impact of mRNA vaccines on this process is not fully understood. Our research shows that SARS-CoV-2 mRNA vaccines alter the epigenetic profile of human macrophages, specifically enhancing histone acetylation, which is linked to immune training. Significant epigenetic changes, along with increased cytokine release, require two vaccine doses. However, these effects diminish over time but can be restored with a booster dose six months later, maintaining a strong pro-inflammatory response.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-11T10:54:03.060794+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000342","title":"A single-cell multi-omic atlas of nodal B-cell non-Hodgkin lymphomas","description":"Nodal B-cell non-Hodgkin lymphomas (B-NHL) are a clinically diverse set of cancers thought to originate from distinct stages of B-cell maturation. To characterize intratumor heterogeneity across B-NHL entities, we performed CITE-Seq (cellular indexing of transcriptomes and epitopes) on 51 lymph node samples including mantle cell lymphoma (MCL, n = 8),  follicular lymphoma (FL, n = 12), germinal center (GCB, n = 5) or activated B-cell (non-GCB/ABC, n = 7) diffuse large B-cell lymphoma (DLBCL) and marginal zone lymphoma (MZL, n = 11) tumors, in addition to non-malignant reactive lymph nodes (rLN, n = 8). We also performed 5 prime scRNA-seq with immune receptor profiling for 11 of these samples (2 rLN, 2 MCL, 3 FL, 2 DLBCL, and 2 MZL).","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-20T16:41:16.6038+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000343","title":"scMultiomics","description":"ARID1B+/+ (control) and ARID1B+/- human telencephalic organoids at D120","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-07T14:30:28.922102+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000344","title":"scRNAseq","description":"ARID1B+/+ (control) and ARID1B+/- human telencephalic organoids at D120","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-07T14:30:26.809546+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000345","title":"Spatially Resolved Tumor Ecosystems and Cell States in Gastric Adenocarcinoma Progression and Evolution","description":"Gastric cancer (GC) is a major cause of global cancer mortality with high levels of heterogeneity, and intratumoral heterogeneity (ITH) represents a significant barrier to GC patient outcomes. In this study, we applied GeoMx DSP technology to identify ITH in GC. We found spatially colocalized RNA-based intratumor subgroups within samples, each correlated with distinct spatially oriented TME and immune profiles.\r\nThe findings broadening our understanding of the spatial and molecular complexity of GC ITH and offering a valuable data resource for future exploration and discovery.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-20T14:18:26.246374+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000346","title":"Multi-omic analysis of SDHB-related PCPG","description":"Hereditary SDHB-mutant pheochromocytomas (PC) and paragangliomas (PG) are rare tumours with a high propensity to metastasize although their clinical behaviour is unpredictable. To characterize the genomic landscape of these tumours and identify metastasis biomarkers, we performed multi-omic analysis on 94 tumours from 79 patients using six molecular methods including: whole-genome sequencing (WGS) of tumour and matched blood (n=94), whole transcriptome sequencing (RNA-seq) (n=91), small-RNA seq (n=90), DNA methylation profiling (n=93). Droplet-based (10x) single nuclei (sn)RNA-seq and snATAC-seq was applied to 9 and 7 cases, respectively. Additionally snATAC-seq was applied to one sample of normal adrenal medulla. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-23T12:28:22.328625+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000347","title":"Orthogonal proteogenomic analysis identifies the druggable PA2G4-MYC axis in 3q26 AML","description":"Our aim was to identify regulators of the EVI1/MECOM gene, which is the most lethal oncogenic TF and is highly expressed in AML with chromosome 3q26 abnormalities.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-17T13:32:54.267149+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000348","title":"WGS of primary neuroblastoma data","description":"Study of ecDNA structure heterogeneity for 13 primary neuroblastoma patients from shallow long-read whole-genome sequencing (MinION platform, WGS mean-coverage 5-10X).","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-04T14:10:33.266233+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000349","title":"WGS of ecDNA neuroblastoma cell lines","description":"ecDNA reconstruction for MYCN-amplified neuroblastoma cell lines using shallow long-read whole-genome sequencing  (MinION platform, WGS mean-coverage 5-10X).","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-04T14:10:35.59871+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000350","title":"Single cell chromatin accessibility allows analysis of the transposable element landscape, revealing shared features of immune tissue-residency","description":"Tissue adaptation is required for regulatory T (Treg) cells to function within organs. Whether this program shares similarities between different tissue-localized immune populations is poorly understood. Here, we addressed this by analyzing single-cell chromatin accessibility data, including the transposable element (TE) landscape, of CD45+ immune cells from different tissues. We identified features of organ-specific tissue adaptation across different immune cells. Focusing on tissue-Treg cells, we\r\nfound that the Treg tissue adaptation program was conserved in other tissue-localized immune cells, such as amphiregulin-producing Th17 cells. Accessible TEs can act as regulatory elements but their contribution to tissue adaptation is unclear. TE landscape analysis revealed an enrichment of specific transcription factor binding motifs in TE regions within accessible chromatin peaks. TEs, specifically from the LTR family, were located in enhancer regions and associated with tissue adaptation. These findings broaden our understanding of immune tissue-residency, an important step towards organ-specific immune interventions.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-14T16:12:05.471043+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000351","title":"Comprehensive genetic landscape, immune checkpoint profiling, and establishment of patient-derived xenograft (PDX) of metachronous brain tumors from constitutive mismatch repair deficiency with a biallelic variant on MSH6","description":"Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare genetic disorder caused by biallelic pathogenic variants in mismatch repair genes (PMS2, MSH6, MLH1, or MSH2) resulting in the development of a variety of different tumors, including brain neoplasms. This study molecularly characterized a Brazilian child with CMMRD, harboring two metachronous brain tumors (medulloblastoma and high-grade glioma), and established a patient-derived xenograft (PDX) of the CMMRD-associated brain tumor.\r\n\r\nKeywords: Brazil, Constitutional mismatch repair deficiency syndrome, exome, MSH6, medulloblastoma, high-grade glioma.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000352","title":"Coloured individuals from South Africa","description":"Genome-wide genotype array data (H3Africa_2017_20021485_A2 and H3Africa_2019_20037295_B1 arrays) of 152 individuals from different locations in South Africa and self-identified as Coloured. From the sites of Graaff-Reinet, Genadendal, Greyton, Nieu-Bethesda, Kranshoek, Prince Albert and Oudtshoorn. ","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-01T15:28:30.064811+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000353","title":"ST dataset of subcortical MS","description":"Spatial transcriptomics from subcortical white matter controls and MS lesions, specifically chronic active (CA) and chronic inactive (CI), that paired with single-nuclei RNA-sequencing  from the same samples , was used to identify spatial niches and key cell interactions driving inflammation and disease progression\r\n\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-17T11:33:36.747413+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000354","title":"snRNA-seq of subcortical MS","description":"Single-nuclei RNA-sequencing (snRNA-seq) from subcortical white matter controls and MS lesions, specifically chronic active (CA) and chronic inactive (CI), that paired with the spatial transcriptomics from the same samples, was used to identify spatial niches and key cell interactions driving inflammation and disease progression.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-17T11:33:34.79643+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000355","title":"Tumor microenvironment-induced FOXM1 regulates ovarian cancer stemness","description":"RNAseq from patient-derived primary tumor cells, cultured or not on organotypic cultures mimicking the tumor microenvironment","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-24T11:42:07.308857+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000356","title":"Novel immunodeficiency caused by homozygous mutations of SLC19A1","description":"The male proband suffered from infancy oral lesions, recurrent fever, diarrhea, vomiting, atopic dermatitis, dark discoloration patches on his skin and lip fissures; he suffered from anemia (megaloblastic), thrombocytopenia, hypogammaglobulinemia and lymphopenia; his growth and development are delayed. Whole exome sequencing identified only one variant predicted to have high impact and to potentially explain the patient’s phenotype, a homozygous missense chr21:46950793:C:T (hg19) SLC19A1 NM_194255:c.1042G>A (p.G348R). Sanger sequencing and segregation analysis confirmed the presence of the homozygous SLC19A1 c.1042G>A (G348R) missense variant in the proband, with a heterozygous state in his family. The same homozygous SLC19A1 variant was identified in a distantly-related male patient with a similar phenotype presentation, while his healthy family members were heterozygous. SLC19A1 is a folate transporter, and thus folic acid supplementation was performed for the proband: platelet counts normalized rapidly and anemia improved; hair and skin discoloration, mouth lesions and chronic diarrhea improved. In contrast, neurological and developmental issues remained unchanged and treatment had only a partial effect on the immune system. This further confirmed the causal role of SLC19A1 for the proband's condition.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[36745868],"external_links":null,"is_released":true,"released_date":"2024-05-29T11:41:35.164005+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000357","title":"scRNAseq of acute myeloid leukemia ","description":"This study analyzes T-cell transcriptional state in acute myeloid leukemia (AML) and \r\nhealthy donors. The goal of the study is to correlate T-cell transcriptional states \r\nabundances with response to chemotherapy. 12 samples (5 baseline and \r\npost-treatment, 2 baseline-only) from AML patients and 3 samples from healthy donors \r\nwere collected and sequenced on Illumina platforms. The files were created using the \r\nGRCh38 reference through CellRanger count (10xGenomics).","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-05-24T11:43:35.911115+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000358","title":"TallFlow - multi-omics","description":"Single-cell Immune profiling 10X genomics protocol. \r\nThis data includes 5' mRNA sequencing, TCR sequencing, and 204 AB sequencing. \r\n\r\nIn total 15 pediatric T-ALL samples and 4 pediatric Thymus samples. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-03T16:02:18.468321+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000359","title":"CRC time course single cell RNA-seq data for QC project","description":"We performed single cell RNA-seq on colorectal cancer (CRC) tumour samples kept on ice for varying time intervals (0h, 2h, 4h, 6h) to simulate sample deterioration after surgery. We also stored the samples in hypothermosol (24h, 72h) to study the effect of storage in sample quality. We performed scRNA-seq on these 6 samples. Six processed samples of varying time points (0h,2h,4h,6h,24h and 72h) right after dissociation were loaded into the Chromium controller system (10X Genomics) with a target of 7,000 cells per well. Barcoded sequencing libraries were generated using the Chromium Single Cell 5′ v1.1 dual index reagent Kit. All libraries were sequenced on an Illumina NovoSeq S4 flowcell until sufficient saturation was reached. We sequenced a total of 47,119 single cells from the six samples. Aligned bam files of the six samples are deposited here. We benchmarked our cell type-specific QC pipeline against conventional and other existing QC pipelines using this data-set.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000360","title":"The evolution of ovarian high grade serous carcinoma from STIC lesions","description":"We performed shallow whole genome sequencing of normal fallopian tube, stroma, p53 signatures, STIL/STIC, invasive and metastasis carcinoma from 5 high grade serous carcinoma cases. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-03T10:02:14.693387+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000361","title":"The evolution of ovarian high grade serous carcinoma from STIC lesions","description":"We performed Ampliseq on 11 samples on a targeted panel of 17 genes.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-03T10:02:17.026619+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000362","title":"Clinical and molecular features of early onset pancreatic cancer","description":"A retrospective cohort study on the clinical and molecular features of early onset pancreatic cancers (i. e. diagnosed at <50 years old) in comparison with later onset tumors.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-03T16:19:08.562944+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000363","title":"CD79B expression in DLBCL","description":"This study proposes a novel association between CD79B expression and cell-of-origin subtypes of DLBCL. Integrative single-cell analyses also revealed a distinct association between germinal center B-cell physiology and the pattern of CD79B expression, which is potentially a key explanation for the variable CD79B expression in DLBCL.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-14T14:00:53.85318+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000364","title":"Dual T2/T17 Transcriptomic Abnormalities Corrected by JAK Inhibition in Refractory Hand Dermatitis","description":"This dataset contains two samples with their FASTQ files. The samples originate from a female patient with refractory hand dermatitis. Sequencing was performed on Illumina NovaSeq instrument.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000365","title":"Single-cell RNA sequencing of human skin tumors (BCC, SCC and Melanoma)","description":"Cancer-associated fibroblasts (CAFs) play a key role in cancer progression and treatment outcome. Here, we elucidate the yet unresolved intra-tumoral CAF variety in three skin cancer types at molecular and spatial single-cell resolution in a large cohort. We show that two out of three CAF subtypes contribute to tumor immune surveillance with distinct mechanisms. Matrix CAFs (mCAFs) ensheath tumor nests and synthesize extracellular-matrix to prevent T cell invasion. Immunomodulatory CAFs (iCAFs), which express proinflammatory and immunomodulatory factors, are only detected in high abundance in aggressive tumors. Strikingly, iCAFs but not tumor cells are (apart from immune cells) the exclusive cell type producing chemokines and, thus, play a key role in immune cell recruitment and activation. Mechanistically, we show that cancer cells transform adjacent healthy fibroblasts into cytokine-expressing iCAFs, which subsequently recruit immune cells and modulate the immune response. In conclusion, targeting CAF variants holds promise for improved efficacy of immunotherapy.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-04T12:56:14.864236+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000366","title":"Base modification analysis using single molecule real-time sequencing","description":"Based on the kinetic characteristics of single-molecule real-time sequencing, we implement a method to directly detect DNA modifications such as 5mC. However, there are room to further improve the accuracy of whole-genome-wide DNA modifications. Therefore, this study aims to utilize deep learning methods for the comprehensive profiling of multiple DNA modifications, including 5mC, 5hmC, and 6mA, using SMRT-seq.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-20T14:10:16.549851+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000367","title":"Targeting Heterochromatin Eliminates Malignant Stem Cells in Chronic Myelomonocytic Leukemia Through Reactivation of Retroelements and Innate Immune pathways","description":"Hematopoietic stem cell (HSC) aging involves heterochromatin reorganization. These repressive marks together with DNA methylation are essential for suppressing transposable elements (TEs). In this study we analyze heterochromatin and transcriptomic changes occurring at genes and TEs in HSCs from chronic myelomonocytic leukemia, a severe myeloid malignancy affecting the elderly, compared to age-matched cells, and in the presence or absence of a combination of epidrugs.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-25T11:36:53.091834+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000368","title":"COVID-19 progression and convalescence in common variable immunodeficiency patients","description":"Longitudinal analysis of single-cell RNAseq datasets of PBMCs from COVID-19 CVID patients and controls.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-06T14:43:41.796691+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000369","title":"RNA-seq analysis of human peri-implantitis samples ","description":"Bulk RNA-seq analysis of human biopsy material collected from implant sites with peri-implantitis. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-17T17:15:16.990996+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000370","title":"CpG methylation changes associated with hyperglycemia in type 1 diabetes occur at angiogenic glomerular and retinal gene loci.","description":"Retinal and glomerular microangiopathy, and cardiovascular disease, contribute to the morbidity and mortality observed in adults with type 1 diabetes (T1D). While the level and duration of hyperglycemia are primary factors influencing these complications, the underlying molecular mechanisms behind glucose-induced organ damage remain poorly understood. In this study, blood samples from young T1D patients at diagnosis and three years later in average were analyzed for DNA methylation using whole-genome bisulfite sequencing. Significant DNA methylation changes in critical angiogenic gene loci were associated with HbA1c, a direct hallmark of chronic hyperglycemia. This finding may offer novel epigenetic insights for a better understanding of T1D complications.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-16T15:48:11.31667+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000371","title":"Genetic subtyping by Whole Exome Sequencing across Diffuse Large B Cell Lymphoma and Plasmablastic Lymphoma.","description":"99 FFPE derived tumor tissue DNA, 9 circulating tumor DNA samples and 38 paired germline DNA were used. A library containing whole exome regions was used to isolate the DNA for sequencing (SureSelect XT  Human All Exon V6 (Agilent technologies)). Sequencing on a NovaSeq 6000 instrument (Illumina, paired end, 2x100, mean 566Gb per FlowCell) at the National Genomic Analysis Center (CNAG, Barcelona, Spain) was performed.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-11T18:25:24.052371+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000372","title":"Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib","description":"Familial gastrointestinal stromal tumors (GIST) are rare.  We present a kindred with multiple family members affected with multifocal GIST who underwent whole genome sequencing of the germline and tumor.  Affected individuals with GIST harbored a germline variant found within exon 13 of the KIT gene, (c.1965T>G; p.Asn655Lys, p.N655K) and a variant in the MSR1 gene (c.877C>T; p.Arg293*, pR293X). Multifocal GISTs in the proband and her mother were treated with preoperative imatinib, and resulted in severe intolerance. The clinical features of multifocal GIST, cutaneous mastocytosis, allergies and gut motility disorders seen in the affected individuals may represent manifestations of the multifunctional roles of KIT in interstitial cells of Cajal or mast cells and/or may be suggestive of additional molecular pathways which can contribute to tumorigenesis.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-15T14:43:07.946419+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000373","title":"Genomic landscape of metastases from 97 patients with metastatic urothelial carcinoma","description":"Metastatic urothelial carcinoma (mUC) is a lethal cancer, with limited therapeutic options. Large-scale studies in early settings provided critical insights into the genomic and transcriptomic characteristics of non-metastatic UC. The genomic landscape of mUC remains however unclear. Whole exome (WES) and mRNA sequencing (RNA-seq) were performed on metastatic biopsies from 111 patients with mUC.  Driver genomic alterations from mUC were comparable to primary UC (TCGA data).","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000374","title":"SDR-seq_06_BCL","description":"Multiomic targeted scDNA-scRNA-seq (SDR-seq) of primary B-cell non-Hodgkin lymphomas. Aim is to link genomci variants to gene expression in single cells. Profiled two follicular lymphoma (FL) primary patient samples and one germinal center subtype diffuse large B-cell lymphoma (GCB) primary patient sample. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-15T14:28:27.985657+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000375","title":"Whole-genome sequences of Korean populations generated by using long- and short-read sequencing technologies.","description":"We newly sequenced whole-genome of Korean participants by using long- and short-read sequencing platforms (n = 3 and n = 100 for long- and short-read sequencing, respectively). With these data, generated by Sequel II HiFi system (Pacific Bioscience) and DNBSEQ-T7 (MGI) sequencers, we identified a set of structural variations common in Korean population as well as the genetic features distinct from other ethnicities.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-17T17:00:09.730595+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000376","title":"cfRRBS data plasma healthy donors","description":"This is cfRRBS data produced from the cfDNA in plasma isolated from healthy, adult donors. Used as a reference for background signal in diseased (onclolytic) plasma cfDNA.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-28T15:20:39.962582+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000377","title":"Diagnosis of pediatric central nervous system tumors using methylation profiling of cfDNA from cerebrospinal fluid","description":"In this study, we explore the potential of classifying pediatric brain tumors based on methylation profiling of the cell-free DNA in cerebrospinal fluid (CSF). For this proof-of-concept study, we collected 20 cerebrospinal fluid samples of pediatric brain cancer patients via a ventricular drain placed for reasons of increased intracranial pressure. For 11 patients in this study we collected matched tumor DNA. This cohort contains fastQ files of cfRRBS data of these samples.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-28T15:20:42.141868+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000378","title":"\"BaTwa\" populations from Zambia retain ancestry of past hunter-gatherer groups","description":"We genotyped and analyzed over two million genome-wide SNPs from two BaTwa populations (40 individuals by population), and from three comparative farming populations (10 to 21 individuals by population) in order to: (i) determine if the Zambian BaTwa carry any genetic material linking them to past hunter-gatherer-groups, and (ii) characterize the genetic affinities of past Zambian hunter-gatherer-groups. We found that both BaTwa populations harbor a hunter-gatherer- like genetic component, representing ∼19% (Bangweulu) and ∼31% (Kafue) of their genetic ancestry, while the rest of their ancestry is similar to western Africans.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-25T14:51:52.282111+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000379","title":"Whole exome sequencing of Ewing and CIC-DUX4 sarcoma tumoroid models","description":"Tumoroid models from Ewing sarcoma and CIC-DUX4 sarcoma models were generated from patient tumor biopsies. Tumoroids were established in 3D matrigel domes and then propagated on a matrige layer. Whole exome sequencing was performed with established tumoroid models.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-28T12:29:26.729107+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000380","title":"RNA sequencing of Ewing and CIC-DUX4 sarcoma tumoroid models","description":"Tumoroid models from Ewing sarcoma and CIC-DUX4 sarcoma models were generated from patient tumor biopsies. Tumoroids were established in 3D matrigel domes and then propagated on a matrige layer. RNA  sequencing was performed with established tumoroid models.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-28T12:29:27.746355+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000381","title":"Epigenetic landscape reorganization and reactivation of embryonic development genes are associated with malignancy in IDH-mutant astrocytoma ","description":"Accurate grading of IDH-mutant gliomas is crucial for determining patient prognosis and guiding treatment decisions. However, histological grading can be challenging, so we aimed to identify objective molecular markers. To this end, we conducted bulk RNA sequencing on primary IDH-mutant astrocytomas (n=138) from the prospective CATNON trial, which evaluated the prognostic impact of adjuvant and concurrent temozolomide. Using this data, we sought to identify molecular markers linked to increased malignancy in IDH-mutant astrocytomas to establish objective grading criteria.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-03T17:21:32.691118+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000382","title":"Characterization of the cellular microenvironment in fibrostenotic Crohn’s disease","description":"Crohn's disease (CD) is marked by recurring intestinal inflammation and tissue injury, often resulting in fibro-stenosis and bowel obstruction, necessitating surgical intervention with high recurrence rates. To elucidate to the mechanisms underlying fibro-stenosis in CD, we analysed the transcriptome of cells isolated from the transmural ileum of CD patients, including a trio of lesions from each patient: non-affected, inflamed, and stenotic ileum samples, and compared them with samples from non-CD patients. Our computational analysis revealed that pro-fibrotic signals from a subset of monocyte-derived cells induced a disease-specific fibroblast population, resulting in chronic inflammation and tissue fibrosis. Our findings suggest that the myeloid-stromal axis may offer a promising therapeutic target to prevent fibro-stenosis in CD.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-13T13:40:48.851859+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000383","title":"AYA glioma NGS","description":"Gliomas are a major cause of cancer-related death in adolescents and young adults (AYA, ages 15-39 years). Different molecular alterations drive gliomas in children and adults leading to distinct biology and clinical consequences. At the convergence of these age groups - the AYA population – little is known about the implications of pediatric vs adult-type alterations. To address this, we analyzed a population-based cohort of 1456 clinically and molecularly characterized gliomas aged 0-39 years. Potentially targetable pediatric-type alterations were found in 31% of AYA gliomas and conferred superior outcomes compared to adult-type alterations. \r\n\r\nThis submission includes the generated NGS data for children, adolescent, and young adults with gliomas. Data includes targeted panel of glioma genes and low-pass WGS (1x coverage).","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-19T17:32:58.739723+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000384","title":"Metagenomic characterization of tracheal aspirates from non-pulmonary sepsis patients","description":"Our previous studies in mechanically ventilated Intensive Care Unit (ICU) patients with extrapulmonary sepsis revealed that pulmonary dysbiosis within 8 h from sepsis diagnosis was associated with ICU mortality. These observations offer promising options that could be technologically adapted to rapidly identify those patients at higher risk of death. However, they relied on 16S rRNA sequencing experiments which impedes deep characterization of the bacterial communities that could help to further substantiate the association. To further discern this association, here we assessed the pulmonary bacterial communities in these patients by leveraging metagenomics and evaluated if the presence of antibiotic resistance genes could explain the higher mortality of the patients.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-24T11:31:33.54685+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000385","title":"TOTHER3","description":"Patritumab deruxtecan in HER2-negative breast cancer: part B results of the window-of-opportunity SOLTI TOT-HER3 trial and biological determinants of early response","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-13T13:40:47.106697+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000386","title":"RNA-sequencing of N-ERD patients with Dupilumab therapy","description":"Transcriptomic profiles of Non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) patients before and after aspirin challenge during 24 weeks of Dupilumab therapy. To investigate the dynamics of nasal mediators during aspirin provocation in N-ERD patients before and twenty-four weeks after therapy with the IL-4 receptor alpha-blocking antibody dupilumab.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-17T09:23:52.316306+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000387","title":"Atezolizumab Plus Chemotherapy With or Without Bevacizumab in Advanced Biliary Tract Cancer: Clinical and Biomarker Data From the Randomized Phase II IMbrave151 Trial ","description":"PURPOSE\r\nBiliary tract cancers (BTCs) harbor an immunosuppressed tumor microenvironment (TME) and respond poorly to PD-1/PD-L1 inhibitors. Bevacizumab (anti-VEGF) plus chemotherapy can promote anticancer immunity, augmenting response to PD-L1 inhibition.\r\nPATIENTS AND METHODS\r\nThis randomized, double-blind, proof-of-concept Phase II study enrolled patients (n=162) with previously untreated advanced BTC (IMbrave151; NCT04677504). Patients were randomized 1:1 to receive 3-weekly cycles of atezolizumab (1200 mg) plus bevacizumab (15 mg/kg) or atezolizumab plus placebo until disease progression or unacceptable toxicity. All patients received cisplatin (25 mg/m2) plus gemcitabine (1000 mg/m2; CisGem) on Days 1 and 8 every 3 weeks for up to 8 cycles. Stratification of patients was by disease status, geographic region, and primary tumor location. The primary endpoint was progression-free survival (PFS). No formal hypothesis testing was performed. Exploratory correlative biomarker analysis was undertaken using transcriptome analysis (n=95) and mutation profiling (n=102) on baseline tumor samples.\r\nRESULTS\r\nBetween February and September 2021, 162 patients were enrolled. Median PFS was 8.3 months in the bevacizumab arm and 7.9 months in the placebo","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-08T12:23:29.43156+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000388","title":"Characterize the regenerative effect of stem cell therapeutics on OA chondrocytes / resident cells by RNA sequencing","description":"With increasing elderly population, lack of effective treatments for aging diseases such as osteoarthritis (OA) imposes a huge burden on individual patients and on European health care systems. Application of stem cells to treat OA has been explored to utilize their therapeutic potential. Results are promising, however, knowledge of the underlying pathways involved in the effect of stem cell therapy on tissue resident cells is lacking. Transcriptome wide analysis of cartilage explants from OA patients treated with hiPSC-derived stem cells were generated and compared to untreated explants to obtain insight into molecular processes involved in response of articular cartilage to stem cell therapy.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000389","title":"Characterizing the secretome of licensed hiPSC-derived MSCs ","description":"Although mesenchymal stromal cells (MSCs) from primary tissues have been successfully applied in the clinic, their expansion capabilities are limited and results are variable. MSCs derived from human-induced pluripotent stem cells (hiMSCs) are expected to overcome these limitations and serve as a reproducible and sustainable cell source. We have explored characteristics and therapeutic potential of hiMSCs in comparison to hBMSCs. Our data qualify hiMSCs as a promising source for cell therapy and/or cell-based therapeutic products. Additionally, the herewith generated database will add to our understanding of the mode of action of regenerative cell-based therapies and could be used to identify relevant potency markers.","abstract":null,"study_type":"RNASeq","pubmed_ids":[36056373],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000390","title":"Resolving complex duplication variants using long read genome sequencing in autism spectrum disorder","description":"The goal of the study is to resolve complex genomic rearrangements in individuals diagnosed with autism spectrum disorder (ASD). Families were identified where at least one individual had previously been diagnosed with ASD, and carried a complex genomic rearrangement as determined by short-read whole genome sequencing. In this study the parents, proband and additional siblings, a total of 20 individuals, were analyzed using Oxford Nanopore Technologies long-read sequencing. Each individual was sequenced on one PromethION flow-cell, providing approximately 25-30X coverage of the genome. The data is deposited as nanopore BAM files with methylation information included. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-15T17:01:12.05694+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000391","title":"\"Distinct immunometabolic signatures in circulating immune cells define disease outcome in acute-on-chronic liver failure\"","description":"We performed single-cell transcriptomics of PBMC’s from healthy (n= 3), acute decompensated (AD) (n= 3) and Acute-on-chronic liver failure (ACLF) patients. \r\nLay Summary: Acute-on-chronic liver failure (ACLF) develops in cirrhotic patients and is characterized by an hyper-inflammatory immune state driving multiple organ failure(s). As a paradox, circulating immune cells also show transcription and metabolic evidence of exhaustion, explaining why these patients are often susceptible to secondary infections. We characterized at a transcriptional level all circulating immune cells of ACLF patiens, and specifically unraveled a distinct recovery and non-recovery ACLF signature within the monocyte population. Moreover, these changes were closely linked to metabolic differences within these cells. The described alterations allowed for a robust prediction of recovery and non-recovery of patients at admission to the hospital.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-26T13:39:23.998668+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000392","title":"RNA-Seq data_MM study cohort (n=73) and human myeloma cell lines","description":"Multiple myeloma (MM) represents approximately 10 % of all hematological malignancies and patients present with a variety of clinical manifestations and diverse cytogenetic backgrounds While MM patient survival has greatly improved due to novel treatments in the last years, the disease is generally considered incurable with a median survival of approximately 6 years. Therapy resistance remains as a major obstacle, causing almost all patients to eventually relapse, underlining the persisting need to identify novel therapeutic targets and biomarkers associated with disease progression. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-07T09:49:31.739299+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000393","title":"Uncovering the potential of circulating tumor DNA for pediatric precision oncology","description":"Pediatric solid high-risk malignancies mostly lack molecular biomarkers for early tumor detection, assessment of minimal residual disease or therapy monitoring. Small patient numbers, limited sample volumes, low tumor mutational burden, and few recurrent alterations in pediatric tumors pose further challenges to liquid biopsy analyses for this patient population. Within the prospective, multinational molecular profiling program INFORM, we collected liquid biopsies from 130 children patients followed by optimized isolation of cell-free DNA (cfDNA). CfDNA was subjected to whole-genome, whole-exome, and targeted panel sequencing applying liquid biopsy-adapted protocols. Integration with tissue-derived molecular information and orthogonal comparison revealed low-coverage whole genome sequencing (lcWGS) as a reliable method for tumor detection. In silico integration of fragment length with differentially weighted genome segment alterations into a ctDNA estimation score (CES) significantly increased sensitivity and specificity to 95% and allowed for plasma-based tumor detection in 93% of patients. Performance of whole exome sequencing (WES) and panel sequencing for detection of molecular targets being predictive for matched treatment responses varied between groups of high-risk entities and cumulative evidence for presence of cancer by all three methods was found in 92% of patients. In-depth analyses for selected patients also demonstrated great the potential of liquid biopsies to decipher temporal and spatial tumor evolution. This study establishes improved methods for liquid biopsy analyses in pediatric oncology and provides the rationale for well-informed implementation of these approaches in future clinical trials to improve the clinical management of high-risk pediatric cancer patients.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-11T11:59:52.390488+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000394","title":"Whole Exome Sequencing of Multiple Myeloma Patients","description":"We used whole exome sequencing (WES) data from 35 MM patients to evaluate possible mutational signatures and driver mutations associated with the patient’s clinical and cytogenetic characteristics. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-26T15:56:57.597413+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000395","title":"Fragmentomics profiling and quantification of plasma Epstein-Barr virus DNA enhance prediction of future nasopharyngeal carcinoma.","description":"This study evaluated the clinical utility of fragmentomics analysis of plasma Epstein-Barr virus (EBV) DNA in nasopharyngeal carcinoma (NPC) screening. The first-round EBV-positive blood samples from a two-round large-scale prospective NPC screening cohort were analyzed. The EBV DNA of subjects who developed NPC in the second round displayed a distinctive mononucleosomal size pattern, an NPC-associated end motif profile, and aberrations in methylation deduced by fragmentomics-based methylation analysis (FRAGMA). Subjects with these aberrant fragmentomics features and higher EBV DNA quantity showed a dramatically increased risk of NPC development, demonstrating the potential of plasma DNA fragmentomics in predicting future cancer risk.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-02T15:55:39.242731+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000396","title":"PD1-targeted delivery of an IL-2 variant induces a multifaceted anti-tumoral T cell response in human lung cancer","description":"To explore PD1-IL2v-specific effects on CD8 and CD4 T cells at a transcriptomic level, we performed single-cell RNA sequencing of patient-derived tumor fragments (PDTFs) which were treated with either Isotype (DP47), Isotype-IL2v (DP47-IL2v), anti-PD1 (PembroPGLALA) or PD1-IL2v (PembroPGLALA-IL2v) for 48 hours. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-17T17:37:13.148721+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000397","title":"Inherited defects of piRNA biogenesis cause transposon de-repression, impaired spermatogenesis, and human male infertility","description":"Effect of biallelic variants in genes of the piRNA pathway on biogenesis of pachytene piRNAs. RNA isolated from snap frozen testicular tissue ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-21T16:03:26.459676+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000398","title":"Patient-derived models of primary breast cancer for preclinical development of novel neoadjuvant therapies","description":"Generation of the first large-scale cohort of mouse intraductal patient-derived xenograft (MIND-PDX) models of primary invasive breast cancer (IBC) and a collection of matched PDX-derived organoids (PDXO) representing all molecular subtypes of IBC, including estrogen receptor (ER-) positive breast cancer. Furthermore, we show that our IBC-MIND cohort can serve as a platform to test experimental neoadjuvant treatment options in different molecular subtypes of breast cancer. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-02-21T17:53:45.617658+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000399","title":"Tracing Endometriosis: Coupling deeply phenotyped, single-cell based Endometrial Differences and AI for disease pathology and prediction","description":"Endometriosis, affecting 1 in 9 women, presents treatment and diagnostic challenges. To address these issues, we generated the biggest single-cell atlas of endometrial tissue to date, comprising 466,371 cells from 35 endometriosis and 25 non-endometriosis patients without exogenous hormonal treatment. Detailed analysis reveals significant gene expression changes and altered receptor-ligand interactions present in the endometrium of endometriosis patients, including increased inflammation, adhesion, proliferation, cell survival, and angiogenesis in various cell types. These alterations may enhance endometriosis lesion formation and offer novel therapeutic targets. Using ScaiVision neural networks, we developed accurate models predicting endometriosis of varying disease severity, including a 11-gene signature-based model. In conclusion, our findings illuminate numerous pathway and ligand-receptor changes in the endometrium of endometriosis patients, offering insights into pathophysiology, targets for novel treatments, and accurate diagnostic models for enhanced outcomes in endometriosis management.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[0],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000400","title":"PROCR-expressing human mammary stem cells give rise to claudin-low breast cancer of poor prognosis","description":"The contribution of mammary stem cells (MaSCs) to tumorigenesis and their clinical implications are still unknown and poorly investigated.  In this study we demonstrate that PROCR-expressing cells are a novel population of MaSC in the human breast.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000401","title":"Excised DNA Circles from V(D)J Recombination Promote Relapsed Leukaemia","description":"In this study, we show that ecDNAs generated from V(D)J recombination replicate and persist through many cell generations. High ecDNA copies at diagnosis of B-cell precursor acute lymphoblastic leukaemia strongly correlate with subsequent relapse. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-30T08:28:52.959291+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000402","title":"Whole Transcriptome Profiling of prDLBCL","description":"Gene expression profiling using RNA-seq was performed using material from 30 patients.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[40402672],"external_links":null,"is_released":true,"released_date":"2024-08-02T13:51:27.251198+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000403","title":"Whole exome sequencing of prDLBCL","description":"To investigate the mutational landscape of prDLBCL, 34 cases were selected for whole exome sequencing.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[40402672],"external_links":null,"is_released":true,"released_date":"2024-09-16T16:36:53.669514+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000404","title":"Targeted DNA sequencing and mRNA sequencing data from patients with peritoneal metastasis from colorectal cancer","description":"Patients with peritoneal metastasis from colorectal cancer (PM-CRC) have inferior prognosis and respond particularly poorly to chemotherapy. This study aims to identify the molecular explanation for the observed clinical behavior and suggest novel treatment strategies in PM-CRC. Tumor samples (230) from a Norwegian national cohort undergoing surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C (MMC) for PM-CRC were subjected to targeted DNA sequencing, and associations with clinical data were analyzed. mRNA sequencing was conducted on a subset of 30 samples to compare gene expression in tumors harboring BRAF or KRAS mutations and wild-type tumors.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-07T14:29:05.463836+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000405","title":"Non-KMT2Ar infant Acute Lymphoblastic Leukemia Sequencing","description":"Integrated genomic analysis of non-KMT2A rearranged infant ALL reveals clinically relevant alterations and common disease origins with childhood ALL.\r\nWhole genome and whole transcriptome sequencing from 21 infant ALL patients with no matched normal DNA sequencing.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-14T15:54:13.134998+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000406","title":"Colorectal cancer functional annotation - MPRA","description":"We performed a Massively Parallel Reporter Assay (MPRA) in colorectal cancer (CRC) cell lines HT29 and SW403 and normal colon cell line HCEC-1CT. We specifically targeted the regions around the CRC GWAS loci to identify which variants alter transcription.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-22T17:14:29.931536+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000407","title":"Excised DNA Circles from V(D)J Recombination Promote Relapsed Leukaemia","description":"In this study, we show that ESCs replicate and persist through many cell generations. High ESC copies at diagnosis of BCP-ALL strongly correlate with subsequent relapse. These data provide the first demonstration that the V(D)J recombination by-product, when replicated to elevated levels, potently associates with the V(D)J recombinase to cause adverse disease outcomes.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-06T16:00:40.448849+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000408","title":"RNA sequencing of OM-ALI cultures derived from control and AD individuals exposed to SARS-CoV-2","description":"RNA sequencing of air-liquid interface (ALI) cultures of olfactory mucosa (OM) cells derived from control (n=3) and AD (n=3) individuals exposed to SARS-CoV-2.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-16T15:50:08.389521+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000409","title":"Fecal microbiota transplantation - Effect of engraftment on plasma metabolomics and cllinical outcomes","description":"Fecal Microbiota Transplantation (FMT) has emerged as a potential modality for mitigating microbiome-associated diseases. Despite this potential, the precise causal pathways by which specific gut microbiota strains induce remission remain inadequately elucidated. In this study, we aimed to discern the impact of engraftment of donor-infused strains on alterations in plasma metabolites, subsequently contributing to the amelioration of clinical parameters involved in subjects with metabolic syndrome (MetSyn) receiving an FMT. We observed that a higher fraction of donor strains engrafted in the recipient is correlated to a reduction in diastolic blood pressure and found specific strains associations through Canonical correlation analysis. Integrating the metabolomics profile show that engraftment of Collinsella aerofaciens and Fusocatenibacter saccharovorans was related to a reduction in 2 oxoarginine in plasma, which was subsequently correlated to a reduction in diastolic blood pressure. In conclusion, we applied a novel framework to elucidate on the complex and heterogenous FMT intervention, establishing a connection between engrafted microbiota and clinical outcome parameters. Our findings underscore the potential therapeutic efficacy of FMT in ameliorating MetSyn, demonstrating a potential contribution of microbial strain engraftment to the improvement of MetSyn via modulation of circulating metabolites.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-22T14:33:32.309317+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000410","title":"RNAseq of medulloblastoma data (MB_COMICS cohort)","description":"Medulloblastoma (MB) is the most common malignant brain tumor in children. It is a neuroectodermal tumor located in the cerebellum. International consensus recognizes four distinct subgroups of MBs including Wingless (WNT), Sonic Hedgehog (SHH), Group 3 (G3), and Group 4 (G4) with distinct molecular characteristics, prognoses, and mortality rates in patients. Here, we have compiled and evaluated a large international MB cohort for which we generated transcriptomic data (RNAseq) for 208 primary MB patient samples.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-11T13:20:39.372025+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000411","title":"Single nuclei ATAC-Seq data from the human ganglionic eminences","description":"We performed the single nuclei Assay for Transposase-Accessible Chromatin with Sequencing (snATAC-Seq) to map potential regulatory genomic regions operating in individual cell populations of the human GE, using these to test for enrichment of schizophrenia common genetic variant liability and to functionally annotate non-coding variants associated with the disorder.   ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[38869145],"external_links":null,"is_released":true,"released_date":"2024-07-01T17:07:51.424984+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000412","title":"Cell-Free DNA Genomic and Fragmentomic Features for Early Outcome Prediction in Diffuse Large B-Cell Lymphoma","description":"Purpose: Diffuse large B-cell lymphoma (DLBCL) patients need an accurate and early risk stratification strategy as prompt therapy escalation may improve outcome.\r\n\r\nPatients and methods: We evaluated cell free DNA (cfDNA) genomic and fragmentomic features in 190 patients with large B-cell lymphoma from more than 40 hospitals in the Benelux using Whole Genome Sequencing (WGS). We defined a new metric called ACT score (Aberrations, Contribution of short fragments, Terminal motif analyses) by combining four cfDNA signals and evaluated its performance to predict end-of-treatment (EOT) response and survival.\r\n\r\nResults: Individual cfDNA features and ACT score were altered per EOT response after one cycle of treatment (T1). The ACT score at T1 outperformed all individual cfDNA features in predicting EOT response (AUC = 0.74). Patients with a positive ACT score had an inferior outcome compared to ACT score negative patients [progression-free survival (PFS): HR 5.0 (95% CI 3.1-8.2), log-rank test, p < 0.0001) and overall survival (OS): HR 6.5 (95% CI 3.5-12.2), log-rank test, p < 0.0001].\r\n\r\nThe 2-year PFS in ACT score positive and negative patients were 29.8% and 78.1%, respectively. The prognostic value of the ACT score is independent of the International Prognostic Index and interim imaging.\r\n\r\nConclusions: ACT score computed from a single plasma sample collected after one cycle of treatment can predict clinical outcome. This low-cost and easy-to-interpret test does not require tissue biopsies or a priori knowledge of mutations and has the potential to aid patient selection in interventional clinical trials and risk-adapted treatment strategies.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-02T17:51:09.267788+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000413","title":"ProstOmics: spatial and bulk multi-omics of prostate cancer","description":"In this ERC-funded ProstOmics project we have used spatial and bulk multi-omics on fresh frozen prostate cancer samples to investigate cancer biology and find for biomarkers to improve patient treatment. All tissue material were collected from prostate cancer patients undergoing radical prostatectomy who had not received any prior cancer-specific treatment.Of the 498 prostate tissue samples (114 patients) included in our project, 176 samples (N=37 patients) have been analyzed with bulk transcriptomics (RNA-seq). Some of these 176 samples were also analyzed with spatial transcriptomics (n=32, N=8, Visium 10x RNA-seq) and DNA methylomics (n=96, N=24, array). All datasets include metadata for histopathological evaluation. Patient metadata include information of age at surgery, time (months) until reported relapse, pre-surgery PSA and post-surgery T-stage.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-06-26T12:57:30.346324+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000414","title":"Whole-genome sequencing of high-retrotransposition rate tumours","description":"We performed whole-genome sequencing of 137 tumours and their matched-normal (adjacent tissue) samples to identify tumours with high rates of somatic retrotransposition","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-01T15:20:49.688035+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000415","title":"Cardiometabolic effects of Anaerobutyricum soehngenii","description":"This study investigated the effects of the probiotic strain Anaerobutyricum soehngenii on plasma metabolites and cardiometabolic parameters. Strain engraftment was determined through strain tracking of fecal metagenomics. Plasma metabolites levels were determined using untargeted metabolomics.\r\nAdditionally the interaction with metformin dose was studied.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-09T09:41:04.502218+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000416","title":"Tumor inflammation and mutational burden are differentially associated with response to nivolumab or nivolumab plus ipilimumab in metastatic colorectal cancer","description":"Nivolumab alone and in combination with ipilimumab demonstrated durable clinical benefit in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer in the phase 2 CheckMate 142 study. Exploratory biomarker analyses of tumor and microbiome samples from CheckMate 142 were performed to evaluate associations between various biomarkers and the efficacy of nivolumab monotherapy and nivolumab plus ipilimumab combination in these patients. Higher expression of inflammation-related gene expression signatures was associated with improved response per investigator assessment and survival benefit with nivolumab monotherapy. In contrast, higher tumor mutational burden, tumor indel burden and degrees of microsatellite instability were associated with improved response per investigator assessment and survival benefit with nivolumab plus ipilimumab. While interpretation is limited by the exploratory nature of these analyses, they suggest that tumor antigenicity rather than baseline tumor inflammation might be important for the combinatorial efficacy. Validation of these findings in larger, randomized studies is necessary.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-14T16:12:21.63926+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000417","title":"DNA methylation database for gynecological cancer detection, classification and assay development","description":"DNA methylation changes are associated with cancer the best predictor of the presence of cancer.\r\nIn order to detect and classify gynecological cancer, we performed MeD-seq to generate DNA methylation profiles of vulvar, cervical, endometrial, fallopian tube and ovarian cancers and their associated healthy tissues.\r\nDNA methylation profiles were used to find general cancer, regional cancer and specific cancer biomarkers that can be used for cancer detection, classification and treatment monitoring.\r\n","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-09T15:35:04.620891+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000418","title":"HeteroFiber (Single muscle fiber heterogeneity)","description":"Individual fibers of human skeletal muscle biopsies - collected at rest.\r\nm. vastus lateralis","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-23T14:16:57.589872+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000419","title":"ExerFiber (Single muscle fiber exercise responses)","description":"Individual fibers of human skeletal muscle biopsies - collected immediately post-exercise and after 3h of recovery.\r\nm. vastus lateralis","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-23T14:16:57.589872+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000420","title":"Fiber type deconvolution from bulk muscle","description":"Bulk human skeletal muscle biopsies - collected at rest.\r\nm. vastus lateralis and gastrocnemius","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000421","title":"Bulk muscle exercise responses","description":"Bulk human skeletal muscle biopsies - collected at rest, immediately post-exercise and after 3h of recovery.\r\nWith placebo, histamine H1 receptor blockade or histamine H2 receptor blockade. \r\nm. vastus lateralis.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000422","title":"Systematic Growth Factor Profiling Platform for 3D Tumor Models Reveals EstradiolResponsive Cellular Mechanisms of Immunotherapy Resistance","description":"Epithelial ovarian cancer (EOC) exhibits significant molecular heterogeneity, which is thought to be influenced by the tumor microenvironment (TME). However, the specific factors driving this heterogeneity remain poorly understood. \r\nIn this study, we integrated growth factoromics and genomic data to identify TME factors contributing to EOC heterogeneity and immunosuppression. Our analysis revealed distinct subgroups of EOC samples with differential responsiveness to specific growth factors, particularly estradiol and R-spondin. Notably, samples with high responsiveness to estradiol and Wnt (C1 cluster) were enriched in the Mesenchymal (MES) molecular subtype, while samples with high responsiveness to R-spondin (C2 cluster) were associated with the Differentiated (DIF) and Immunoreactive (IMR) subtypes. We discovered that the G protein-coupled estrogen receptor (GPER), rather than the classical estrogen receptor alpha (ERα), was the key mediator of estrogen responsiveness and a determinant of molecular subtype classification. Single-cell sequencing analysis identified subsets of estrogen-responsive malignant cell (MAL.PDCD5) and cancer-associated fibroblast (FB.TNFSF10), which were associated with immunosuppressive patterns in the TCGA cohort. Importantly, the interaction between these cell populations significantly increased upon estrogen treatment, suggesting a potential mechanism by which estrogen signaling may contribute to the development of an immunosuppressive TME. \r\nOur findings highlight the critical role of estrogen signaling in shaping the molecular heterogeneity and immunosuppressive TME of EOC and provide novel insights into potential therapeutic targets for overcoming immunosuppression in this malignancy.\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-24T13:08:37.666862+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000423","title":"Genome-wide array data from Eivissan and Menorcan Individuals","description":"22 and 20 genome-wide array data for Eivissan and Menorcan healthy unrelated volunteers, respectively. The affymetrix Human Origins array was used to genotype these individuals. The variant set was lifted over to the hg38 human genome reference. A single gziped VCF file can be found.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-09T09:34:44.609785+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000424","title":"Adipose tissue macrophage dysfunction is associated with a breach of vascular integrity in NASH","description":"Our study describes for the first time the myeloid cell landscape in human visceral adipose tissue at single-cell level within a cohort of well-characterized patients with non-alcoholic fatty liver disease. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[37977244],"external_links":null,"is_released":true,"released_date":"2024-07-15T16:45:34.155142+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000425","title":"Heterogeneity and evolution of DNA mutation rates in microsatellite-stable colorectal cancer","description":"A mutation accumulation experiment in colorectal cancer (CRC) derived tumoroids, aimed at measuring the spontaneous rates of accumulation of new single-nucleotide sequence variations in seven microsatellite stable CRCs and one microsatellite unstable CRC. Mutations accumulated over six+six months were identified via whole genome sequencing of clonal tumoroids. 150x WGS for 7 samples.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-09T09:32:45.727185+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000426","title":"Prediction of homologous recombination deficiency identifies colorectal tumors sensitive to PARP inhibition","description":"BRCAness is a well-established feature in breast, ovarian, prostate and pancreatic carcinomas, our recent findings indicate that up to 15% of colorectal cancers (CRC) also harbor defects in the HR pathway, presenting promising opportunities for innovative therapeutic strategies in CRC patients. We developed a new tool called HRDirect, which builds upon the HRDetect algorithm and is able to predict HRD from reference-free tumor samples. We validated HRDirect using matched breast cancer and CRC patient samples. Subsequently, we assessed its efficacy in predicting response to the PARP inhibitor olaparib by comparing it with two other commercial assays: AmoyDx HRD by Amoy Diagnostics and the TruSight Oncology (TSO) _500 HRD panel by Illumina NGS technology. While all three approaches successfully identified the most PARPi-sensitive CRC models, HRDirect demonstrated superior precision in distinguishing resistant models compared to AmoyDX and TSO500-HRD, which exhibited overlapping scores between sensitive and resistant cells. Furthermore, we propose integrating HRDirect scoring with ATM immunohistochemical analysis as part of our \"composite biomarker approach\" to enhance the identification of HRD tumors, with an immediate translational and clinical impact for CRC personalized treatment. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-26T18:11:30.981421+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000427","title":"Cergentis FFPE-TLC","description":"In this study, formalin-fixed paraffin-embedded targeted locus capture (FFPE-TLC) sequencing is used as a novel technology for targeted detection of tumor-specific genomic structural variants (SVs) in the primary tumor of 29 colorectal cancer patients with metastatic disease. The tumor region was macrodissected and sequenced for 29 patients, and the \"normal\" region of the same slide was macrodissected and sequenced for 8 of these patients. \r\n\r\nSVs were found in the common fragile site (CFS)-associated genes MACROD2, PRKN, FHIT and WWOX as well as SVs caused by three LINE transposable elements. Tumor-specificity of selected SVs was independently verified by droplet digital PCR of tumor tissue DNA and their applicability as plasma circulating tumor DNA biomarkers was demonstrated.","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-24T12:50:13.035546+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000428","title":"Whole Exome Sequences from Eivissan and Menorcan Individuals","description":"We analyzed Exome sequences of present day Eivissan and Menorcan individuals in order to expand on the knowledge about their demographic history and its functional consequences.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-11T12:14:29.901425+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000429","title":"Whole-exome sequencing of acute myeloid leukemias with aberrations of chromosome 7","description":"Deletions and partial losses of chromosome 7 are frequent in acute myeloid leukemia (AML) and are often linked to dismal outcome. However, the genomic landscape and prognostic impact of concomitant genetic aberrations remain incompletely understood. Therefore, we performed whole-exome sequencing of acute myeloid leukemias (N = 60) with aberrations of chromosome 7.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-10T12:11:10.224599+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000430","title":"WES analysis of tumor samples","description":"Whole exome sequencing was performed on paired tumor (N=8) from ER+ advanced breast cancer, obtained prior to combined CDK4/6i and endocrine therapy and at disease progression. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-15T10:39:51.621965+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000431","title":"Whole-genome and transcriptome versus panel sequencing in precision oncology: A translational-clinical comparison","description":"Precision oncology offers new cancer treatment options. While the use of whole-genome (WGS) and transcriptome (TS) sequencing remains often confined to specific clinical programs, molecular analysis with gene panels is more common clinical practice. Methods: Twenty patients with rare or advanced tumors sequenced by WGS/TS within the DKFZ/NCT/DKTK-MASTER program from 2015 to 2020 (MASTER 1) were additionally sequenced with the TSO500 DNA and TST170 RNA Assay by Illumina. Original Molecular Tumor Board (MTB) therapy recommendations (TR) were juxtaposed with TR from NGS panel data analysis (comparison 1). To mitigate temporal differences between the two sequencings, WGS/TS was bioinformatically reanalyzed (MASTER 2), and new TR were again compared (comparison 2). Results: In comparison 1, 47.1% of the MASTER 1’s TR and 62.8% of the panel’s TR were identical, as were 45.9% of the TR of MASTER 2 and 54.9% of the panel in comparison 2. In both MASTER 1 and MASTER 2, 26.5% and 36.1% of TR, respectively, relied on Biomarkers (BM) which were not covered by the panel. Eight of the ten MTB-derived therapy implementations were also supported in the panel, the two remaining ones being based on BM absent from the panel. Conclusions: About half of the TR in WGS/TS and panel sequencing were identical. Around a third of TR issued by WGS/TS were based on BM which are not covered by the panel, leading to therapy implementations. The presented data underscores the clinical value of comprehensive molecular analyses in individuals with advanced cancers.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-24T11:53:02.693005+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000432","title":"Single-cell RNA sequencing of pediatric Hodgkin Lymphoma to study the inhibition of T cell subtypes  ","description":"Here, we applied single-cell RNA-sequencing (scRNA-seq) on isolated HRS cells and the immune cells from the same cHL tumors. This allowed us to identify genes of cell surface proteins that are consistently overexpressed in HRS cells and can potentially be used as targets for antibody-drug conjugates or CAR T cells. Finally, we identify potential interactions by which HRS cells inhibit T cells, among which the Galectin-1/CD69 and HLA-DRA/LAG3 interactions. However, high levels of inter-patient heterogeneity of the interaction strength were observed. In conclusion, this study identifies new potential therapeutic targets for cHL and highlights the importance of studying heterogeneity when identifying therapy targets.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-02T13:48:16.37229+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000433","title":"Indolent nodal T follicular helper cell lymphomas—A case series","description":"Nodal TFH (nTFH) cell lymphomas are aggressive and treated with multiagent chemotherapy. We describe, however, a series of patients who lived over a year without the need for chemotherapy, meriting future studies to delineate a potential subset of indolent disease","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000434","title":"Highly similar genomic landscapes in monoclonal B-cell lymphocytosis and ultra-stable chronic lymphocytic leukemia with low frequency of driver mutations","description":"whole genome sequencing of MBL and CLL","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[29449433],"external_links":null,"is_released":true,"released_date":"2024-09-19T15:54:39.902791+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000435","title":"Identifying New Genetic Subtypes in Follicular Lymphoma","description":"Follicular lymphoma (FL) exhibits considerable variability in biological features and clinical trajectories across patients. To dissect the diversity of FL, we utilized a Bernoulli mixture model to identify genetic subtypes in 713 pre-treatment tumor tissue samples. Our analysis revealed the existence of five subtypes with unique genetic profiles that correlated with clinicopathological characteristics. The clusters were enriched in specific mutations as follows: CS (CREBBP and STAT6), TT (TNFAIP3 and TP53), GM (GNA13 and MEF2B), Q (quiescent, for low mutation burden), and AR (mutations of mTOR pathway-related genes). The subtype Q was enriched for patients with stage I disease and was associated with a lower proliferative history compared to the other subtypes. The AR subtype was unique in its enrichment for IgM-expressing FL cases and was associated with advanced-stage and more than 4 nodal sites. The existence of subtypes was validated in an independent cohort of 418 samples from the GALLIUM trial. Notably, patients assigned to the TT subtype consistently experienced inferior progression-free survival when treated with immunochemotherapy. Collectively, our findings offer insight into core pathways distinctly linked with each FL cluster and are expected to be informative in the era of targeted therapies.\r\n\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-06T10:43:48.546195+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000436","title":"Mind the gap: the relevance of the genome reference to resolve rare and pathogenic inversions","description":"Chromosomal inversions (INV) are particularly challenging to detect due to their copy-number neutral state and association with repetitive regions. Inversions represent about 1/20 of all balanced structural chromosome aberrations and can lead to disease by gene disruption or altering regulatory regions of dosage sensitive genes in cis. Short-read genome sequencing (srGS) can only resolve ~70% of cytogenetically visible inversions referred to clinical diagnostic laboratories, likely due to breakpoints in repetitive regions. Here we study twelve inversions by srGS (n=3) or long read genome sequencing (lrGS) (n=9)","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-23T11:04:20.386936+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000437","title":"FLT3-targeting and places FLT3 as an ideal therapeutic target to selectively eradicate LSCs, while sparing HSC.","description":"CRISPR/Cas9 FLT3 knock-out (FLT3-KO) in human HSCs and LSCs followed by functional xenograft assays to test their ability to regenerate human hematopoiesis and leukemia, respectively. \r\nFLT3-KO in HSCs from human fetal liver, cord blood and adult bone marrow showed no impairment in multilineage hematopoiesis in primary and secondary xenografts. By contrast, FLT3-KO LSCs from 6 of 7  FLT3-ITD mutated AMLs were able to generate short-term engraftment but were completely exhausted by 12 weeks. Thus, FLT3 is essential for LSC long-term propagation. This dependency was unique to FLT3-ITD AML samples as non-FLT3-ITD AML samples generated leukemic grafts upon FLT3-KO. Transcriptomic analysis revealed that FLT3-KO induced downregulation of DNA repair and cell cycle checkpoints, uniquely in FLT3-ITD AML, but not in healthy HSCs or other AMLs.\r\nOur research highlights a critical distinction between healthy HSCs and LSCs: whereas healthy hematopoiesis proceeds unperturbed upon FLT3-KO, FLT3-ITD leukemogenesis is impaired through elimination of LSCs. This evidence underscores the necessity for more potent FLT3-targeting and places FLT3 as an ideal therapeutic target to selectively eradicate LSCs, while sparing HSC.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-03T10:16:03.181088+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000438","title":"Whole exome sequencing of pre-invasive lung adenocarcinoma in non-smokers","description":"The prevalence of lung adenocarcinoma (LUAD) has increased sharply in East Asia. Early diagnosis leads to better survival rates, but this requires an improved understanding of the molecular changes during early tumorigenesis, particularly in non-smokers. We performed whole exome-sequencing and RNA-sequencing for samples from 94 East Asian patients with precancerous lesions (25 with atypical adenomatous hyperplasia [AAH]; 69 with adenocarcinoma in situ [AIS]) and 73 patients with early invasive lesions (minimally invasive adenocarcinoma [MIA]). Cellular analysis revealed that the activities of endothelial and stromal cells could categorize tumors into molecular subtypes within pathology-defined lesion types. These subtypes were linked with the advanced radiology-defined lesion type and coordinated with immune cell infiltration throughout the progression of LUAD. Characterization of these lesion types identified positively selected mutation patterns, and suggested that angiogenesis of the late-stage AIS type potentially contributes to tissue invasion of the MIA type. Our findings offer a novel resource that may help to improve early diagnosis and patient prognosis, and also suggest possible approaches for early disease interception.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-20T14:09:19.026503+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000439","title":"Transcriptomics sequencing analysis of pre-invasive lung adenocarcinoma in never-smokers","description":"The prevalence of lung adenocarcinoma (LUAD) has increased sharply in East Asia. Early diagnosis leads to better survival rates, but this requires an improved understanding of the molecular changes during early tumorigenesis, particularly in non-smokers. We performed whole exome-sequencing and RNA-sequencing for samples from 94 East Asian patients with precancerous lesions (25 with atypical adenomatous hyperplasia [AAH]; 69 with adenocarcinoma in situ [AIS]) and 73 patients with early invasive lesions (minimally invasive adenocarcinoma [MIA]). Cellular analysis revealed that the activities of endothelial and stromal cells could categorize tumors into molecular subtypes within pathology-defined lesion types. These subtypes were linked with the advanced radiology-defined lesion type and coordinated with immune cell infiltration throughout the progression of LUAD. Characterization of these lesion types identified positively selected mutation patterns, and suggested that angiogenesis of the late-stage AIS type potentially contributes to tissue invasion of the MIA type. Our findings offer a novel resource that may help to improve early diagnosis and patient prognosis, and also suggest possible approaches for early disease interception.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-20T14:09:19.026503+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000440","title":"Nanopore sequencing of blood, saliva, buccal mucosa samples of patients with inherited retinal disorders","description":"X-linked genetic disorders typically affect females less severely than males due to the presence of a second X chromosome not carrying the deleterious variant. However, the phenotypic expression in females is highly variable, which may be explained by an allelic skew in X chromosome inactivation. Accurate measurement of X inactivation skew is crucial to understand and predict disease phenotype in carrier females, with prediction especially relevant for degenerative conditions.\r\n\r\nWe propose a novel approach using nanopore sequencing to quantify skewed X inactivation accurately. By phasing sequence variants and methylation patterns, this single assay reveals the disease variant, X inactivation skew, its directionality, and is applicable to all patients and X-linked variants. Enrichment of X-chromosome reads through adaptive sampling enhances cost-efficiency. Our study includes a cohort of 16 X-linked variant carrier females affected by two X-linked inherited retinal diseases: choroideremia and RPGR-associated retinitis pigmentosa. As retinal DNA cannot be readily obtained, we instead determine the skew from peripheral samples (blood, saliva and buccal mucosa), and correlate it to phenotypic outcomes. This revealed a strong correlation between X inactivation skew and disease presentation, confirming the value in performing this assay and its potential as a way to prioritise patients for early intervention, such as gene therapy currently in clinical trials for these conditions. \r\n\r\nOur method of assessing skewed X inactivation is applicable to all long-read genomic datasets, providing insights into disease risk and severity and aiding in the development of individualised strategies for X-linked variant carrier females.\r\n","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-23T09:28:25.451413+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000441","title":"Copy number variations and fragmentation features in cell-free DNA predict response in advanced non-small cell lung cancer patients under anti-PD-(L)1 therapy","description":"Anti-PD-(L)1 therapy is routinely used in metastatic NSCLC. However, response rates vary and biomarkers predicting treatment efficacy are lacking. Liquid biopsies allow monitoring of residual disease during therapy. Residual circulating tumor DNA (ctDNA) after therapy represents a predictive marker for adverse outcome. Here, we assessed copy number variations (CNVs) in serial plasma samples of NSCLC patients receiving PD-(L)1 blockade. We profiled CNV and fragmentation features in 118 plasma samples of advanced NSCLC patients by low-coverage whole genome sequencing taken at baseline, after four therapy cycles and at disease progression. CNVs and fragment features (i.e., fragment length, end motifs, position) were significantly altered in patients compared to healthy donors. Furthermore, fragment length changes at baseline and residual CNVs after four therapy cycles correlated with short progression-free survival. Our results highlight the suitability of plasma-based CNV and fragment analysis for disease monitoring and as a predictive marker for response duration in NSCLC patients under anti-PD-(L)1 therapy.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-26T18:45:50.727581+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000442","title":"Diagnostic yield and clinical utility of whole-exome sequencing in pediatric patients with rare and undiagnosed diseases in the Czech Republic","description":"In our single-center study, we have launched a pilot program for pediatric patients\r\nwith undiagnosed diseases in the second-largest university hospital in the Czech Republic.\r\nWES was implemented as a first-line test after inclusion in the study as part of the diagnostic\r\nworkflow.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-23T09:19:59.583273+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000443","title":"Duplex sequencing","description":"An additional 320 buccal swab samples were subjected to error-corrected sequencing (duplex sequencing).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-23T09:30:19.978492+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000444","title":"A 3D genome atlas of breast cancer progression (BRCA3D)","description":"In this study, we aimed to understand how the 3D genome changes during breast cancer development and progression, in situ. Towards this goal, we collected cells from patient biopsies and performed Hi-C on four types of biopsies representing different stages of disease progression: healthy mammary tissue, primary breast tumours, liver metastasis and malignant pleural effusions. We survey the changes in the 3D genomes at the level of structural variation, compartments and TADs, as well as ERα associated distal interactions. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-05T12:23:49.184822+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000445","title":"RNAseq of CYLD cutaneous syndromes","description":"CYLD cutaneous syndrome (CCS)  skin tumours develop from puberty onwards, can number in the hundreds and progressively grow over time. This study examines the role of non-canonical NF-kB signaling in CCS. The study combines primary patient samples of CYLD tumours and bulk RNAseq.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000446","title":"plasma DNA LINE-1 targeted bisulfite sequencing: a new non-invasive multi-cancer detection marker","description":"The detection of circulating tumor DNA, which allows non-invasive tumor molecular profiling and disease follow-up, promises optimal and individualized management of patients with cancer. However, detecting small fractions of tumor DNA released when the tumor burden is reduced remains a challenge. We developed a PCR-based targeted bisulfite method coupled to deep sequencing to detect methylation patterns of L1PA elements,which we named DIAMOND (for Detection of Long Interspersed Nuclear Element Altered Methylation ON plasma DNA).  We used sodium bisulfite chemical conversion to achieve base-pair resolution analysis and designed a multiplexed PCR based on 8 amplicons covering L1PAs . ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-26T10:14:10.103164+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000447","title":"Indonesian Genome Diversity Project 3","description":"Low coverage whole genome sequences were collected to study the population history in Eastern Indonesia, in particular Wallacea and Papua region. We have sequenced the genomes of 254 individuals from 12 Wallacean and 3 Papuan populations spanning this geographical region.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-04T09:05:07.840354+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000448","title":"RNA Sequencing of AD OM cells exposed to traffic-related air pollutants","description":"Total RNA sequencing of olfactory mucosa (OM) cells derived from individuals diagnosed with Alzheimer's disease exposed to traffic-related ultrafine particles (UFPs) for 24-h and 72-h in submerged cultures. The UFPs used for exposures were: A0, A20 and Euro6. Exposures were compared to the corresponding blank samples.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-25T16:23:47.223573+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000449","title":"Personalized peptide vaccination among 173 patients with IDH wildtype glioblastoma: a retrospective analysis","description":"Tumors from 173 GBM patients were analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens. Exome libraries for 173 glioblastoma tumors and matched normal DNA were sequenced on Illumina platform, alongside whole transcriptomes from the tumor samples.\r\n\r\nPaper Abstract: Current treatment outcome of patients with glioblastoma (GBM) remains poor. Following standard therapy, recurrence is universal with limited survival. GBM tumors from 173 patients were analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens. Among all patients, including 70 treated prior to progression (primary) and 103 treated after progression (recurrent), the median overall survival from first diagnosis was 31.9 months (95% CI: 25.0-36.5). Side effects were infrequent and were predominantly grade 1 or 2. A vaccine-induced immune response to at least one of the vaccinated peptides was detected in blood samples of 87 of 99 (88%) monitored patients. T-cell responses to vaccinated neoepitope peptides were durable in most patients. Significantly prolonged survival was observed for patients with multiple vaccine-induced immune responses (53 months) compared to those with no/low induced responses (27 months; P=0.03). Altogether, our results highlight that the application of personalized neoantigen-targeting peptide vaccine is feasible and represents a promising potential treatment option for GBM patients.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-02T13:18:16.851643+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000450","title":"cfDNA Methylomes for HCC Detection and Postoperative Monitoring","description":"To overcome the limitations of current ctDNA-based HCC detection, specifically mutational profiling, we propose quantifying cfDNA methylation levels using cfMeDIP-seq and evaluating its capacity for HCC detection and post-surgery recurrence monitoring. This approach aims to reveal the clonal dynamics of HCC during surgery and upon relapse. Our preliminary data and analyzed results demonstrate that tumor-agnostic cfDNA methylomes can accurately detect HCC and predict recurrence after liver resection or transplantation. This method could have significant implications for the diagnosis, treatment, and monitoring of HCC.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-07-31T17:19:37.635842+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000451","title":"Genome-wide SNP data of Fulani populations from the Sahel belt","description":"This project seeks to uncover the genetic structure and ancestry of the Fulani populations across the Sahel/Savannah Belt. The study includes two datasets (''WGA_Fulani_Database'' and ''Saliva_Fulani_Ddatabase''), and SNP-genotyping data was generated using the Illumina Infinium H3Africa Consortium array (BeadChip type: H3Africa_2019_20037295_B1) in two genotyping batches (TE-2559_201029 and TE-2559_201020). In total, 419 were genotyped for this study and the key results were presented in Fortes-Lima et al. 2024 (doi: 10.1101/2024.06.22.600206).\r\n","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-28T14:15:38.118603+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000452","title":"Genome and transcriptome sequencing of cancer of unknown primary tumours","description":"Genome and transcriptome sequencing of cancer of unknown primary tumours was used to determine yield of clinical biomarkers for a molecular guided trial or for resolving cancer type of origin. This study includes profiling of germline DNA and tumour DNA by whole genome sequencing of tissue and cfDNA biopsies, as well as targeted genome sequencing using two panels, including Comprehensive cancer panel (CCP) and TruSight Oncology 500 (TSO500). This study also includes profiling of tumour RNA by whole transcriptome sequencing.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-02T13:56:18.026536+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000453","title":"An Enterochromaffin Cell Atlas of the Human Gut","description":"build an atlas of epithelial cells in the human gut\r\nhealthy patients and patients with Crohn's disease (with or without IBS symptoms)","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000454","title":"Bulk RNAseq - Calprotectin in vitro effects on human early hematopoiesis","description":"To explore the effects of calprotectin (CAL) on early hematopoiesis, we incubated CD34+ cells from four healthy donors for 7 days in the presence of stem cell factor (SCF), FLT3-ligand and thrombopoietin (TPO) without and with CAL, interleukin-6 (IL6) and the IL6_CAL combination before collecting cells. We performed the same experiment with CD34+ cells collected from three patients with JAK2-V617F-mediated myelofibrosis (MF). A total of 135,545 cells from healthy donors and 111,725 cells from myelofibrosis patients were analyzed by single-cell RNA sequencing (scRNA-seq) using the 10X Chromium droplet-based platform.\r\n\r\nBulk RNAseq 4 conditons : \r\n-Control\r\n- Calprotectin\r\n- IL-6\r\n- Calprotectin+IL-6\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-28T11:46:46.559396+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000455","title":"Single cell RNAseq 7 days - Calprotectin in vitro effects on human early hematopoiesis","description":"To explore the effects of calprotectin (CAL) on early hematopoiesis, we incubated CD34+ cells from four healthy donors for 7 days in the presence of stem cell factor (SCF), FLT3-ligand and thrombopoietin (TPO) without and with CAL, interleukin-6 (IL6) and the IL6_CAL combination before collecting cells. We performed the same experiment with CD34+ cells collected from three patients with JAK2-V617F-mediated myelofibrosis (MF). A total of 135,545 cells from healthy donors and 111,725 cells from myelofibrosis patients were analyzed by single-cell RNA sequencing (scRNA-seq) using the 10X Chromium droplet-based platform.\r\n\r\nSingle cell RNAseq 7 days - Normal and tumor samples\r\n\r\n4 conditons : \r\n-Control\r\n- Calprotectin\r\n- IL-6\r\n- Calprotectin+IL-6","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-28T11:46:46.559396+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000456","title":"Bulk ATACseq 7days - Calprotectin in vitro effects on human early hematopoiesis","description":"To explore the effects of calprotectin (CAL) on early hematopoiesis, we incubated CD34+ cells from four healthy donors for 7 days in the presence of stem cell factor (SCF), FLT3-ligand and thrombopoietin (TPO) without and with CAL, interleukin-6 (IL6) and the IL6_CAL combination before collecting cells. We performed the same experiment with CD34+ cells collected from three patients with JAK2-V617F-mediated myelofibrosis (MF). A total of 135,545 cells from healthy donors and 111,725 cells from myelofibrosis patients were analyzed by single-cell RNA sequencing (scRNA-seq) using the 10X Chromium droplet-based platform.\r\n\r\nBulk ATACseq 7days - Normal and tumor samples\r\n\r\n4 conditons : \r\n-Control\r\n- Calprotectin\r\n- IL-6\r\n- Calprotectin+IL-6","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-28T11:46:46.559396+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000457","title":"ATAC sequencing of Treg cell subsets","description":"Within the investigator-initiated clinical trial Charact-IL-2 (ClinicalTrials.gov Identifier: NCT03312335), we treated 12 female systemic lupus erythematosus patients with low-dose interleukin-2. From this study we identified four distinct interleukin-2-driven regulatory T (Treg) cell subsets. This study aimed at defining chromatin accessability and predict transcriptional regulation of HLA-DR– CD38– Treg cells, HLA-DR+ CD38– Treg cells, HLA-DR– CD38+ Treg cells, and HLA-DR+ CD38+ Treg cells. Treg cell subsets were isolated from 500ml blood pooled from four healthy donors by flow cytometry sorting.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[39137779],"external_links":null,"is_released":true,"released_date":"2024-08-13T13:37:27.174245+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000458","title":"RNA sequencing of circulating human immune cells before and after interleukin-2 immunotherapy in systemic lupus erythematosus patients","description":"Within the investigator-initiated clinical trial Charact-IL-2 (ClinicalTrials.gov Identifier: NCT03312335), we treated 12 female systemic lupus erythematosus patients with low-dose interleukin-2. Patients received 4 cycles of 5 daily injections of 1.5 million international units interleukin-2 over 9 weeks. This study aimed at investigating interleukin-2-induced transcriptional changes in circulating human immune cells, and to define changes in T cell receptor clonality before and after interleukin-2 immunotherapy. For this purpose, blood was collected from patients before and after each treatment cycle.","abstract":null,"study_type":"RNASeq","pubmed_ids":[39137779],"external_links":null,"is_released":true,"released_date":"2024-08-13T13:37:24.042961+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000459","title":"Cellular Dynamics Upon Immune Checkpoint Inhibition","description":"Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, yet most patients experience limited or no clinical benefit. To elucidate the mechanisms of response and resistance, we analyzed single-cell RNA-sequencing data from 141 patients across multiple cancer types and ICI treatment modalities, with longitudinally paired samples. Using a robust, integration-free deep phenotyping framework, we annotated 876,410 cells into 80 granular states. We identified consistent compositional changes in 17 cell subtypes following ICI treatment, including enhanced adaptive immune responses and reduced interferon-responsive cells. Co-regulated cell communities within the tumor microenvironment (TME) highlighted coordinated interplay between immune and non-immune components. Importantly, we discovered two distinct patient groups with divergent TME dynamics post-treatment: responders showed expansion of naive lymphocytes, while non-responders exhibited increased immune-experienced/suppressive cells. This dichotomy offers a potential predictive biomarker for patient stratification. Our comprehensive analysis of TME dynamics during ICI treatment advances understanding of response mechanisms and personalized cancer immunotherapy.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-28T10:34:09.59008+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000460","title":"Mosaic structural variation sample ","description":"Mosaic Normal-Tumor genomes are generated from real normal-tumor pairs with validated somatic variants. In this case, validated variants from the GRIDSS2 paper. \r\n\r\nMosaic genomes were generated using GenomeMosaicMaker, an open-source software tool designed and implemented for this specific purpose. The variants provided in the VCF truth file for each mosaic tumor/normal pair were annotated using funnSV for SVs and VEP for SNVs and indels. All CRAM files are aligned to GRCh37. Please see https://github.com/EUCANCan/oncoliner and  https://github.com/Computational-Genomics-BSC/GenomeMosaicMaker for more information. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[34253237],"external_links":[{"url": " https://github.com/EUCANCan/oncoliner ", "name": "EucanImage", "label": "ONCOLINER"}, {"url": " https://github.com/EUCANCan/oncoliner ", "name": "EucanImage", "label": "ONCOLINER"}],"is_released":true,"released_date":"2024-08-14T11:19:40.25421+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000467","title":"Single cell RNA sequencing of co-culture of human organoids with polarized pro-inflammatory (M1) or anti-inflammatory (M2) macrophages","description":"Human intestinal organoids co-cultured with pro-inflammatory (M1) or anti-inflammatory (M2) human macrophages for 48 hours. 3 days after the co-culture alive cells were sorted and processed for single cell RNA sequencing\r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-02-25T12:19:52.44976+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000468","title":"A first step towards clinical routine long-read sequencing in Sweden, a national pilot study on chromosomal rearrangements ","description":"Here, the Genomic Medicine Sweden Rare Diseases (GMS-RD) consortium validated HiFi Revio long-read whole genome sequencing (lrGS) for clinical digital karyotyping of SVs nationwide. The first 16 samples included in this study were collected from all health care regions in Sweden. We established a national pipeline and a shared variant database for variant calling and filtering. The included validation samples cover a spectrum of simple and complex SVs including inversions, translocations and copy number variants.  ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-23T11:04:21.379915+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000469","title":"Transcriptome analysis of human iPSC-derived microglia in a novel human 3D cortical tissue model","description":"scRNA-seq analysis of human iPSC-derived microglia in a novel, human in vitro 3D cortical tissue model. Samples include three distinct conditions (each as biological duplicates): wild-type microglia extracted from cultures after 1 month (WT_1mo) and 3 months (WT_3mo) of culturing, as well as knock-in microglia extracted from cultures carrying three familial AD mutations in the APP gene (Swedish, Iberian, Arctic; introduced by CRISPR/Cas9-mediated knock-in) after 3 months of culturing (KI_3mo).","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-23T16:07:43.860401+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000470","title":"Integrating molecular imaging and transcriptomic profiling in advanced HER2-positive breast cancer receiving trastuzumab emtansine (T-DM1): an analysis of the ZEPHIR clinical trial ","description":"Purpose: The ZEPHIR clinical trial evaluated the role of [89Zr]trastuzumab-PET/CT (HER2-PET/CT) and 2-[18F]fluoro-2-deoxy-D-glucose PET/CT ([18F]FDG-PET/CT) in predicting outcomes in patients with advanced HER2-positive breast cancer treated with trastuzumab emtansine (T-DM1). Here, we combined molecular/metabolic imaging and transcriptomic data to investigate the biological processes associated with [89Zr]trastuzumab and [18F]FDG uptake, and to dissect the mechanisms involved in T-DM1 resistance.\r\nExperimental design: RNA was extracted from metastasis biopsies obtained at study inclusion in the ZEPHIR trial. HER2-PET/CT and [18F]FDG-PET/CT imaging data of biopsied lesions were integrated with RNA sequencing data. Lesions were compared based on the level of [89Zr]trastuzumab uptake (dichotomized into high/low classes) as well as on the presence/absence of metabolic response, defined comparing baseline and on-treatment [18F]FDG-PET/CT. \r\nResults: We analyzed matched transcriptomic and molecular/metabolic imaging data for 24 metastases (one lesion/patient). Pathways involved in extracellular matrix (ECM) organization, glycosylphosphatidylinositol synthesis, and collagen formation were enriched in lesions presenting low [89Zr]trastuzumab uptake. [18F]FDG uptake at baseline correlated with proliferation and immune-related processes. Hypoxia and ECM-related processes were enriched in lesions that showed no metabolic response to T-DM1. Interestingly, immune-related processes (e.g., Fc gamma receptor activation, complement cascade) were associated with high [89Zr]trastuzumab uptake and metabolic response.\r\nConclusions: To our knowledge, this study represents the first correlative analysis between [89Zr]trastuzumab tumor uptake and gene expression profiling in humans. Our findings point toward a role of ECM in impairing [89Zr]trastuzumab tumor uptake and T-DM1 metabolic response in advanced HER2-positive breast cancer, and highlight the potential of molecular imaging to depict tumor microenvironment features.\r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-21T10:31:26.609293+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000471","title":"Plasma mutation profile of precursor lesions and colorectal cancer using the Oncomine Colon cfDNA Assay","description":"Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Early detection of precursor lesions or early-stage cancer could hamper cancer development or improve survival rates. Liquid biopsy, which detects tumor biomarkers, such as mutations, in blood, is a promising avenue for cancer screening. To assess the presence of genetic variants in plasma cell-free tumor DNA from patients with precursor lesions and colorectal cancer using the commercial Oncomine Colon cfDNA Assay. Cell-free DNA (cfDNA) samples from the blood plasma of 52 Brazilian patients were analyzed. Eight patients did not have any significant lesions (five normal colonoscopies and three hyperplastic polyps), 24 exhibited precursor lesions (13 nonadvanced adenomas, ten advanced adenomas, and one sessile serrated lesion), and 20 patients with cancer (CRC). The mutation profile of 14 CRC-associated genes were determined by next-generation sequencing (NGS) using the Oncomine Colon cfDNA Assay in the Ion Torrent PGM/S5 sequencer.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-16T10:39:02.441456+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000472","title":"Genomic Determinants of Response to CAR-T Therapy in Diffuse Large B Cell Lymphoma","description":"Diffuse large B-cell lymphoma (DLBCL) is one of the most common forms of blood cancer worldwide. Outcomes for patients with relapsed or refractory (r/r) DLBCL have remained dismal. Chimeric antigen receptor (CAR) T-cell therapy targeting the B-cell surface marker CD19 has recently emerged as a novel, effective approach capable of producing durable responses in r/r DLBCL patients. Indeed, nearly all r/r DLBCL patients in the United States are considered candidates for FDA-approved CAR-T therapy. However, CAR-T therapy has a number of major shortcomings. First, it has limited efficacy. The median progression-free survival (PFS) of r/r DLBCL patients treated with CAR-T therapy is roughly six months. Second, it has major toxicities. CAR-T therapy is associated with risk of life-threatening side effects such as cytokine release syndrome (CRS) and CAR-T cell-related encephalopathy syndrome (CRES). Third, it is highly expensive. Strategies for identifying, a priori, those patients likely to respond to this therapy could provide an important tool for clinical decision-making and improving outcomes in patients with r/r DLBCL. Here, we enrolled a real-world cohort of 161 r/r DLBCL patients treated with CAR-T therapy and applied whole exome and transcriptome sequencing on their pre-treatment biopsies to identify predictors of outcome. We found that genomic signatures reflecting both tumor cells and the microenvironment were highly associated with response to CAR-T therapy. Clinical application of our findings could provide an effective strategy for risk stratification and precision medicine approaches to help those patients most likely to respond to this effective but toxic and expensive therapy.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000473","title":"RNA-Seq of human longitudinal whole blood samples from PCR-positive and PCR-negative recent household contacts of COVID-19 index cases.","description":"Little is known about the transcriptomic profile of individuals who are exposed to SARS-CoV-2 yet resist becoming PCR positive.  To investigate this, longitudinal whole-blood samples were taken (0, 7, 14, and 28 days after enrolment) from PCR positive and PCR negative SARS-CoV-2-naïve household contacts who were recently exposed to a COVID-19 index. Samples were also taken from pre- and post-pandemic unexposed controls. Total RNA was extracted from PAXgene tubes before undergoing poly(A) selection followed by globin and rRNA depletion. DNA libraries were constructed using the NEBNext® Ultra™ II Directional RNA Library Prep Kit for Illumina. All samples were then sequenced across 2 flowcells of an Illumina HiSeq 4000.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-04T12:09:22.525857+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000474","title":"PCNSL single-cell dataset","description":"This dataset includes 4 samples with scRNA-seq and 3 sample with CITE-seq, scTCR-seq and scBCR-seq.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-08T11:04:38.107839+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000475","title":"Spatial transcriptomics analysis of triple negative breast cancers","description":"While triple negative breast cancer (TNBC) is known to be heterogeneous at the genomic and transcriptomic levels, spatial information on tumor organization and cell composition is still lacking. Here, we investigated TNBC tumor architecture including its microenvironment using spatial transcriptomics on a series of 92 patients. We performed an in-depth characterization of tumor and stroma organization and composition using an integrative approach combining histomorphological and spatial transcriptomics. Furthermore, a detailed molecular characterization of tertiary lymphoid structures led to identify a gene signature strongly associated to disease outcome and response to immunotherapy in several tumor types beyond TNBC. A stepwise clustering analysis identified nine TNBC ecotypes, further validated in external datasets. Several ecotypes were associated with disease outcome and characterized by potentially actionable features. In this work, we provideThis is  the largest TNBC series providing a comprehensive insight into the complexity of TNBC ecosystem with potential clinical relevance, opening avenues for treatment tailoring including immunotherapy. \r\n\r\nAll the processed data needed to replicate the results from the publication (counts, images, clinical data, etc) are available on Zenodo:\r\nhttps://zenodo.org/records/14204217","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[39592577],"external_links":null,"is_released":true,"released_date":"2024-08-30T15:32:55.265355+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000476","title":"USH genes sequencing ","description":"Sequencing of a panel including the whole genomic sequence of Usher genes.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-16T11:06:28.244844+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000477","title":"Drug Development against Tumor Microtube Networks in Glioblastoma","description":"Glioblastomas are aggressive brain tumors that resist current therapies by hijacking neurodevelopmental programs to invade the brain and form resilient multicellular networks. Tumor Microtubes (TMs), neurite-like processes extended by cancer cells,  drive this pathobiology, but TM-inhibiting drugs are lacking. Here we developed a comprehensive, combined in vitro and in vivo drug screening approach, including novel AI-based analysis tools of TM parameters. Two Protein Kinase C (PKC) activators, TPPB and PMA, exhibited robust inhibition of TM formation in cell-based assays. Since unconnected glioblastoma cells exhibit increased sensitivity to cytotoxic therapy in vivo, brain tumor-bearing mice received TPPB, the most consistent TM-inhibiting compound, in combination with radiotherapy. Long-term intravital 2-photon microscopy confirmed anti-TM and anti-tumor effects of the co-treatment. Mechanistically, TPPB treatment inhibited several key molecular and functional components of TM-related glioblastoma cell network communication and decreased the expression of TTYH1, a key driver of invasive TMs. By establishing a novel screening pipeline for anti-TM drug development, our study identifies a druggable TM master regulator pathway and a small molecule with robust anti-TM effects. It provides a proof-of-principle that disrupting TMs and disconnecting tumor networks is a pharmacologically feasible strategy to make therapies against glioblastoma more effective.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-29T12:24:58.687986+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000478","title":"Ballett","description":"TSO500 study: The project, called \"BALLETT\" (Belgian Approach of Local Laboratory Extensive Tumor Testing), has a double goal: (1) show the relevance of broad molecular profiling to improve oncological patients care, (2) demonstrate that broad molecular testing can be performed in a decentralized setting by local diagnostics laboratories in a fully standardized and uniform way while complying with the highest quality standards.\r\nNCT05058937\r\n\r\nThe publication number is: Your manuscript ID is bcr-2023-256124. Title: CUP and BRAF V600E meeting the BEACON combination.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-26T15:48:01.011237+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000479","title":"The carbonyl nucleobase adduct M3Ade is a potent antigen for adaptive polyclonal MR1-restricted T cells","description":"\"Background: M3Ade is a cell endogenous carbonyl adduct of adenine that binds MR1, supports MR1-mediated stimulation of multiple non-MAIT MR1-reactive T cells (MR1T) in vitro and allows ex-vivo identification of MR1Ts via the usage of an MR1-tetramer  loaded with M3Ade (MR1-M3Ade tetramer).\r\nGoals: to characterize MR1-M3Ade tetramer positive cells by performing single-cell RNA sequencing (scRNA-seq) and single-cell T Cell Receptor sequencing (scTCR-seq) of MR1-M3Ade tetramer positive T cells from PBMCs of 6 healthy donors and of MR1-M3Ade tetramer negative T cells from PBMCs of 5 of the same 6 donors.\r\nDetails: This EGA study contains the raw data sequencing files for both the scRNA-seq and the scTCR-seq samples.\"","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-23T11:15:54.810459+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000480","title":"snRNA and snATAC analysis of cocaine use disorder in human caudate nucleus","description":"We investigated cell type specific changes of gene expression and chromatin accessibility in the caudate nucleus of N=6 individuals with and N=8 individuals without cocaine use disorder using postmortem human brain samples. We performed single-nuclei RNA-sequencing and single-nuclei ATAC sequencing in the same cells using the 10xMultiome platform. The N=14 tissue donors were of African-American ancestry. The cohort consists of N=5 female and N=9 male individuals. ","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-28T12:38:58.332757+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000481","title":"Identification and characterisation of pathogenic and non-pathogenic FGF14 repeat expansions","description":"Repeat expansions in FGF14 cause autosomal dominant late-onset cerebellar ataxia (SCA27B) with estimated pathogenic thresholds of 250 (incomplete penetrance) and 300 AAG repeats (full penetrance), but the sequence of pathogenic and non-pathogenic expansions remains unexplored. Here, we demonstrate that STRling and ExpansionHunter accurately detect FGF14 expansions from short-read genomic data using outlier approaches. By combining long-range PCR and nanopore sequencing in 169 patients with cerebellar ataxia and 802 controls, we compare FGF14 expansion alleles, including interruptions and flanking regions. Uninterrupted AAG expansions are significantly enriched in patients with ataxia from a lower threshold (180-200 repeats) than previously reported based on expansion size alone. Conversely, AAGGAG hexameric expansions are equally frequent in patients and controls. Distinct 5' flanking regions, interruptions and pre-repeat sequences correlate with repeat size. Furthermore, pure AAG (pathogenic) and AAGGAG (non-pathogenic) repeats form different secondary structures. Regardless of expansion size, SCA27B is a recognizable clinical entity characterized by frequent episodic ataxia and downbeat nystagmus, similar to the presentation observed in a family with a previously unreported nonsense variant (SCA27A). Overall, this study suggests that SCA27B is a major overlooked cause of adult-onset ataxia, accounting for 23-31% of unsolved patients. We strongly recommend re-evaluating pathogenic thresholds and integrating expansion sequencing into the molecular diagnostic process.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[39227614],"external_links":null,"is_released":true,"released_date":"2024-08-26T16:13:03.650758+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000482","title":"Isatuximab and Cemiplimab in Relapsed or Refractory Extranodal Natural Killer/T-Cell Lymphoma","description":"Relapsed or refractory extranodal NK/T-cell lymphoma (R/R ENKTL) still shows poor prognosis due to limited treatment options. Although immune checkpoint inhibitors have been explored as salvage treatments due to its prevalent PD-L1 expression, their single-agent activity has been unsatisfactory. This phase II study evaluated the efficacy and safety of cemiplimab, an anti–PD1 antibody and isatuximab targeting CD38 which is another target of ENKTL in R/R ENKTL. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000483","title":"Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer","description":"Neoadjuvant immune checkpoint blockade (ICB) has shown unprecedented activity in mismatch repair deficient (MMRd) colorectal cancers, but its effectiveness in MMRd endometrial cancer (EC) remains unknown. In this investigator-driven, phase I, feasibility study (NCT04262089), 10 women with MMRd EC of any grade, planned for primary surgery, received two cycles of neoadjuvant pembrolizumab (200 mg IV) every three weeks. A pathologic response (primary objective) was observed in 5/10 patients, with 2 patients showing a major pathologic response. No patient achieved a complete pathologic response. A partial radiologic response (secondary objective) was observed in 3/10 patients, 5/10 patients had stable disease and 2/10 patients were non-evaluable on Magnetic Resonance Imaging (MRI). All patients completed treatment without severe toxicity (exploratory objective). At median duration of follow-up of 22.5 months, two non-responders experienced disease recurrence. In-depth analysis of the loco-regional and systemic immune response (predefined exploratory objective) showed that monoclonal T cell expansion significantly correlated with treatment response. Tumour-draining lymph nodes displayed clonal overlap with intra-tumoural T cell expansion. All pre-specified endpoints, efficacy in terms of pathologic response as primary endpoint, radiologic response as secondary outcome and safety and tolerability as exploratory endpoint, were reached. Neoadjuvant ICB with pembrolizumab proved safe and induced pathologic, radiologic, and immunologic responses in MMRd EC, warranting further exploration of extended neoadjuvant treatment.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-26T16:15:47.288249+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000484","title":"Early detection of ovarian cancer using cell-free DNA fragmentomes and protein biomarkers","description":"Ovarian cancer is the leading cause of death from gynecological cancers worldwide. No effective screening methods exist, and tumors are commonly detected at advanced stages where treatment is much less effective.  In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome and protein biomarker (CA-125 and HE4) analyses to evaluate 591 women from the European Union or the United States with ovarian cancer, benign adnexal masses, or without ovarian lesions.  Using a machine learning model that incorporated multi-analyte fragmentome data and protein measurements, we detected ovarian cancer with high specificity >99% and sensitivity of 72%, 69%, 87%, and 100% for stages I–IV, respectively (AUC=0.96, 95% CI: 0.94-0.99), including 90% of high grade serous ovarian cancers.  At the same specificity, CA-125 alone detected 34%, 62%, 63%, and 100% of ovarian cancers for stages I–IV (p=0.001, two-sided test of equal proportions).  Additionally, our approach distinguished benign masses from ovarian cancers with high accuracy (AUC of 0.88, 95% CI=0.83-0.92).  These results were validated in an independent population.  These findings show that integrated cfDNA fragmentome and protein analyses detect ovarian cancers with high performance, enabling a new accessible approach for noninvasive ovarian cancer screening and diagnostic evaluation.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-27T11:57:01.347441+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000485","title":"A Genomics-Driven Artificial Intelligence-Based Model Classifies Breast Invasive Lobular Carcinoma and Discovers CDH1 Inactivating Mechanisms","description":"We developed an artificial intelligence (AI)-model applied to histological images using CDH1 biallelic mutations, pathognomonic for breast invasive lobular carcinoma (ILC), as ground truth. We evaluated the performance of the AI-model to predict the presence of CDH1 biallelic mutations and to diagnose ILC. Subsequently, we investigated the molecular underpinning cases of predicted by the model to harbor a CDH1 biallelic mutations but lacking these alterations according to targeted sequencing. Among this analyses, we subjected to whole genome sequencing (WGS) one ILC case lacking CDH1 biallelic mutations by targeted sequencing and lacking CDH1 promoter methylation to determine the molecular basis of its lobular phenotype.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-26T10:11:40.009067+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000486","title":"resistance mechanims to targeted therapies from DNA sequencing","description":"WES of tumor tissue biopsies collected at resistance to molecular targeted agents","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-16T10:14:39.519288+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000487","title":"resistance mechanims to targeted therapies from RNA sequencing","description":"WTS of tumor tissue biopsies collected at resistance to molecular targeted agents","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-16T10:14:39.519288+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000488","title":"Disease recurrence after pathologic response (Recurrence DNAseq)","description":"In this study we aim to gain insight into the mechanisms of immune evasion after initial pathologic response to neoadjuvant immune checkpoint inhibition in macroscopic stage III melanoma by pooling data of the neoadjuvant OpACIN, OpACIN-neo and PRADO trials(EGAD00001012116, EGAS00001004832, EGAD00001006730, EGAS50000000268). Therefore we analyzed in-depth paired baseline(n=10) and recurrent tumor samples of the lymph nodes(n=10) and brain metastasis (n=2) through Whole Exome Sequencing (WES) analyses. Additionally we incorporated transcriptome sequencing data from 22 patients (21 paired-end samples and one single end sample)","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-29T10:11:53.830734+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000489","title":"Transcriptomic changes in placenta associated with anesthesia, delivery mode and maternal diabetes","description":"The goal of this study was to analyse the impact of maternal diabetes and other maternal factors such as birth mode and anaesthesia on placental transcriptomics. Placental tissue samples from both, the villous and the decidua were prepared and RNAseq was conducted; samples were from mothers with Type1 Diabetes or gestational diabetes or from control mothers. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-16T11:57:46.630236+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000490","title":"Ischemia Reperfusion Responses in Human Lung Transplants at the Single Cell Resolution","description":"Ischemia reperfusion is an unavoidable step of organ transplantation. Development of therapeutics for lung injury during transplantation has proved challenging; understanding lung injury from human data at the single cell resolution is required to accelerate the development of therapeutics. Donor lung biopsies from six human lung transplant cases were collected at the end of cold preservation and 2-hour reperfusion and underwent single cell RNA sequencing. Donor and recipient origin of cells from the reperfusion timepoint were deconvolved. Gene expression profiles were (1) compared between each donor cell type between timepoints and (2) compared between donor and recipient cells. Inflammatory responses from donor lung macrophages were found after reperfusion with upregulation of multiple cytokines and chemokines, especially IL-1 and IL-1. Significant inflammatory responses were found in alveolar epithelial cells (featured by CXCL8) and lung endothelial cells (featured by IL-6 upregulation). Different inflammatory responses were noted between donor and recipient monocytes and CD8+ T cells. The inflammatory signals and differences between donor and recipient cells observed provide insight into the cellular and molecular mechanisms of ischemia reperfusion induced lung injury. Further investigations may lead to the development of novel targeted therapeutics.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-30T08:36:35.99054+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000491","title":"Arcagen - Skin cancer domain","description":"Arcagen is an EORTC/SPECTA pan-European project that aims to recruit 1000 rare cancer patients from different tumour domains of EURACAN. This study collected samples from advanced or metastatic rare cancer from patients older than 12, and analysed them using Foundation Medicine next-generation sequencing (NGS) panels (FoundationOne CDx for FFPE samples or FoundationOne Liquid CDx for blood samples). Here we are submitting the dataset that contain NGS files patients diagnosed with adnexal carcinoma of the skin, Merkel cells cancer, and malignant melanoma of the uvea (n=49).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-02T14:12:12.963261+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000492","title":"Immune signature of malignant melanoma in pregnancy","description":"Melanoma is a highly immunogenic malignancy and there is a deep-rooted notion among clinicians that a probable systemic immunosuppressed state during pregnancy would negatively influence melanoma related prognosis. To test this hypothesis on a more fundamental level, we collected a unique set of melanoma tumor samples and performed RNAseq to draw comparisons between the immune cell infiltrate of pregnant patients and non-pregnant matched controls. We found that there is indeed no differential expression of any immune cell subset. This underscores the notion that the supposed immunosuppressive state of pregnancy does not hamper the anti-tumor immune response. \r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-02T16:13:54.174673+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000493","title":"Mate-pair sequencing of 12q-amplified osteosarcomas","description":"Mate-pair sequencing of 12q-amplified osteosarcomas for the detection of structural variants. This was carried out in order to study the structure of the chromosome 12q-amplicons and whether material from other chromosomes is also intertwined and amplified in a bid to further characterise these tumours beyond CDK4 and MDM2 amplification. Mate-pair data was also used to verify gene fusions detected with RNA-seq.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-09T15:58:42.104593+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000494","title":"RNAseq of 12q-amplified osteosarcomas","description":"RNA-seq of 12q-amplified osteosarcomas for detection of gene fusions and gene expression analysis. RNA-seq was used to look for novel gene fusions and promoter swapping events, and study the expression levels of identified 3' partners. Additionally, global gene expression patterns were used to separate cases into clusters.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-09T15:58:42.104593+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000495","title":"Longread sequencing of selected 12q-amplified osteosarcomas","description":"Longread sequencing of selected 12q-amplified osteosarcomas for verification of SV data. This was carried out in order to verify findings from mate-pair sequencing regarding the structure of the chromosome 12q-amplicons and whether material from other chromosomes is also intertwined and amplified in a bid to further characterise these tumours beyond CDK4 and MDM2 amplification.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-09T15:58:42.104593+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000496","title":"Mid-pass Whole-genome Sequencing in a Malagasy Cohort Uncovers Body Composition Associations","description":"The majority of human genomic research studies have been conducted in European-ancestry cohorts, reducing the likelihood of detecting potentially novel and globally impactful findings. Here, we present mid-pass whole-genome sequencing data and a genome-wide association study in a cohort of 264 self-reported Malagasy individuals from three locations on the island of Madagascar. We describe genetic variation in this Malagasy cohort, providing insight into the shared and unique patterns of genetic variation across the island. We observe phenotypic variation by location, and find high rates of hypertension particularly in the Southern Highlands sampling site as well as elevated self-reported malaria prevalence in the West Coast site relative to other sites. After filtering to a subset of 214 minimally-related individuals, we find a number of genetic associations with body composition traits, including many variants that are only observed in African populations or populations with admixed African ancestry from the 1000 Genomes Project. This study highlights the importance of including diverse populations in genomic research for the potential to gain novel insights, even with small cohort sizes. This project was conducted in partnership and consultation with local stakeholders in Madagascar and serves as an example of genomic research that prioritizes community engagement and that has potential impacts on our understanding of human health and disease.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[39169618],"external_links":null,"is_released":true,"released_date":"2024-09-02T16:19:14.189924+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000497","title":"Bladder cancer subtyping study across 4 atezo clinical trials","description":"Checkpoint inhibitors targeting the PD-1/PD-L1 interaction have revolutionized cancer therapy across many indications. In urothelial carcinoma (UC), several PD-1/PD-L1 inhibitors have been approved for treatment in localized and metastatic disease. While these agents provide durable clinical benefit in a number of patients, the majority do not respond. A better understanding of the molecular mechanisms underlying response and resistance is needed to tailor existing treatments and develop new therapeutics in UC. We profiled tumors from 2803 patients from four late-stage randomized clinical trials evaluating the PD-L1 inhibitor atezolizumab in metastatic UC and muscle-invasive bladder cancer by RNA-seq, a targeted DNA panel, immunohistochemistry, and digital pathology. A machine learning algorithm identified four UC transcriptional subtypes, representing luminal desert, stromal, immune, and basal tumors. Overall survival benefit from atezolizumab over standard-of-care was observed in immune and basal tumors (45% of patients). Digital pathology showed enrichment of human interpretable features in specific molecular subtypes, and a self-supervised approach could classify molecular subtypes from H&E slides with high accuracy, suggesting that machine-based image interpretation could accelerate tumor molecular profiling. Somatic alterations showed limited capacity to identify responders. Finally, mechanisms of benefit with PD-L1 blockade appeared different in immune and basal tumors, with immune tumors benefiting from B/plasma cell enrichment, while basal tumors benefited from granulocyte enrichment. This study represents the largest integration of UC molecular and curated clinical data in randomized clinical trials to date, paving the way for prospective clinical studies tailoring treatment regimens to specific tumor molecular subtypes in UC and other indications.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-03T10:38:50.303376+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000498","title":"RNA-seq in LCLs derived from constitutional MLH1 epimutation carriers and non-carrier relatives","description":"Transcriptome profiling in human lymphoblastoid cell lines derived from constitutional MLH1 epimutation carriers and non-carrier relatives","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-22T16:10:31.548895+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000499","title":"ATAC-seq, H3K27ac CUT&Tag, and UMI-4C in LCLs derived from constitutional MLH1 epimutation carriers and non-carrier relatives","description":"ATAC-seq, H3K27ac CUT&Tag, and UMI-4C in lymphoblastoid cell lines derived from constitutional MLH1 epimutation carriers and non-carrier relatives","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-22T16:10:30.394507+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000500","title":"WGS of constitutional MLH1 epimutation carriers and non-carrier relatives","description":"WGS of constitutional MLH1 epimutation carriers and non-carrier relatives","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-22T16:10:29.089727+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000501","title":"Spatially resolved niche and tumor microenvironmental alterations in gastric cancer peritoneal metastases","description":"Peritoneal metastases (PM) in gastric cancer (GC) portend a poor prognosis, yet our understanding of tumor microenvironmental (TME) characteristics associated with GCPM remain limited. Here, we analyzed intrinsic genomic alterations and transcriptomic programs predictive of GCPM in a prospective cohort of 248 patients, identifying CDH1, PIGR, and ELF3 mutations as predictors. By inspecting the spatial dynamics of the TME, we find that tumor compartment infiltration of pro-tumorigenic cell types such as inflammatory cancer-associated fibroblasts (CAFs) predict peritoneal recurrence. Next, in a cross-sectional study of 205 samples from 55 patients, distinct pathways and immune compositions in GCPM relative to liver metastases highlight the TME's significance in transcoelomic metastases. Notably, several putative therapeutic targets exhibited distinct expression patterns between PTs and PMs. Our findings highlight transcriptomic variations and niche reprogramming in the GCPM peritoneal environment, revealing roles of myeloid dendritic cells, effector memory CD8+ T cells, and CAFs in metastatic progression.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-16T11:16:16.739068+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000502","title":"3D tissue engineered human skeletal muscle modelling Facioscapulohumeral Muscular Dystrophy","description":"acioscapulohumeral muscular dystrophy (FSHD) is caused by sporadic misexpression of the transcription factor double homeobox 4 (DUX4) in skeletal muscles. So far, monolayer cultures and animal models have been used to study the FSHD disease mechanism and for FSHD therapy development, but these models do not fully recapitulate the disease and there is a lack of knowledge on how DUX4 misexpression leads to skeletal muscle dysfunction. To overcome these barriers, we have developed a 3D tissue engineered skeletal muscle (3D-TESM) model by generating genetically matched myogenic progenitors (MPs) from human induced pluripotent stem cells of three mosaic FSHD patients. 3D-TESMs derived from genetically affected MPs recapitulate pathological features including DUX4 and DUX4 target gene expression, smaller myofiber diameters, and reduced absolute forces upon electrical stimulation. RNA sequencing data illustrates increased expression of DUX4 target genes in 3D-TESMs compared to 2D myotubes, and cellular differentiation was improved by 3D culture conditions. Treatment of 3D-TESMs with small molecules identified in drug development screens in 2D muscle culture showed no improvements in contractile force and sarcomere organization, highlighting the potential benefit of 3D-TESMs for preclinical drug potency screening by eliminating false-positive compounds for FSHD research and drug development.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-27T11:18:10.489274+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000503","title":"DUX4 activates novel intergenic transcripts and isoforms in a tissue-specific context","description":"DUX4, a transcription factor driving zygotic genome activation during the embryonic cleavage stage in mammals, regulates the expression of genic and non-genic elements and modulates chromatin accessibility. Its misexpression in skeletal muscle causes Facioscapulohumeral muscular dystrophy (FSHD). The sporadic expression of DUX4 in FSHD muscle and the limitations of short-read RNA sequencing challenge, however, a comprehensive grasp of its consequences on the muscle transcriptome. Here, leveraging full-length isoform RNA sequencing with short-read RNA sequencing on DUX4-inducible myoblasts, we elucidated DUX4-induced transcriptomic changes within a myogenic context. DUX4 yields a complex transcriptome featuring numerous unannotated isoforms from known and novel loci. Moreover, we observed distinct isoform usage of DUX4 target genes between myogenic and embryonic cleavage states highlighting the distinct differences between DUX4 transcription factor activity in skeletal muscle and during the cleavage stage. We also identified ~1,400 unannotated intergenic isoforms predominantly originating from repetitive elements such as LTRs, LINEs, and SINEs. Integration with available datasets delineates the transcriptional and epigenetic landscape of these loci across myogenic and embryonic backgrounds. Like the cell type-specific isoform production, the usage of DUX4 binding sites at these intergenic loci is in part cell type-specific. Collectively, these findings demonstrate substantial and context-specific transcriptomic alterations induced by DUX4 further enriching our understanding of DUX4-induced muscle pathology.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-27T11:18:11.778039+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000504","title":"The landscape of Usher syndrome-associated transcript isoforms in the human neural retina","description":"Usher syndrome is an autosomal recessively inherited disorder characterized by the combination of progressive loss of visual function due to retinitis pigmentosa, sensorineural hearing loss and vestibular dysfunction in a subset of cases. Usher syndrome is clinically and genetically heterogeneous. To date, eleven genes have been identified that are associated with Usher syndrome. It is known that these genes express multiple isoforms, however, for most of the known isoforms their relative importance in the human retina is unknown. To fill this gap, using PacBio long-read mRNA sequencing we aimed to provide an overview of the Usher syndrome transcripts in the human retina.  ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-02T16:21:26.061778+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000505","title":"Oncogene activated human breast luminal progenitors contribute basally located myoepithelial cells","description":"Basal-like breast cancer originates in luminal progenitors, frequently with an altered PI3K pathway, and focally in close association with genetically altered myoepithelial cells at the site of tumor initiation. The exact trajectory behind this bi-lineage phenomenon remains poorly understood. Here we used a breast cancer relevant transduction protocol including hTERT, shp16, shp53, and PIK3CA(H1047R) to immortalize FACS isolated luminal cells, and we identified a candidate multipotent progenitor. We found that the apparent luminal phenotype of these oncogene transduced progenitors was metastable giving rise to basal-like cells dependent on culture conditions.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-18T17:49:42.122363+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000506","title":"SCLC MeDIP","description":"Mimicry of neuronal features are emerging as malignant regulators of cancer growth and metastasis. Neuroendocrine (NE) cancers and small cell lung cancers (SCLC) in particular have been shown to share expression profiles marking various stages of neuronal differentiation. \r\nHere, methylation profile from SCLC patients' tumour and normal tissue has been investigated genome wise.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-12T14:47:35.20624+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000507","title":"Androgen activity in the normal male embryonic hindbrain drives lethal PFA ependymoma","description":"PFA ependymoma is an unusual infantile brain tumor with few somatic mutations, thought to be driven by epigenetic mechanisms. PFA ependymomas have a markedly higher incidence, and a worse prognosis in males as compared to female infants. Here we show that the cellular hierarchy of male PFA is less differentiated than female PFA. Androgen supplementation promotes the growth of PFA ependymoma. We conclude that androgen signaling in both the normal developing hindbrain, and PFA ependymoma are both necessary and sufficient to promote growth and delay differentiation. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000508","title":"Sex Differences in MAGEL2 Gene Promoter Methylation in High Functioning Autism - Trends from a Pilot Study Using Nanopore Cas9 Targeted Long Read Sequencing","description":"Using DNA extracted from peripheral blood, Cas9-targeted nanopore DNA sequencing was used to analyze MAGEL2 gene, including its entire regulatory construct (chr15:23639316-23651466), for sequence variation and 5-methyl-cytosine (5mC) modification in a cohort of adults with HFA compared to sex- and age-matched NC. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-08-30T08:27:33.681422+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000509","title":"ecDNA copy number heterogeneity","description":"Neuroblastoma exhibits significant inter- and intra-tumour genetic heterogeneity and varying clinical outcomes. Here, we used DNA and RNA sequencing from the same single cells in cell lines and neuroblastoma patients to investigate these effects. We reveal extensive intercellular ecDNA copy number heterogeneity. We also provide direct evidence of how this heterogeneity influences the expression of cargo genes, including MYCN and its downstream targets, and the overall transcriptional state of neuroblastoma cells.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-16T11:11:28.567182+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000510","title":"Comprehensive genomic characterization of early stage bladder cancer - nanopore sequencing","description":"For this project about non-muscle invasive bladder cancer (NMIBC), we analysed long read sequencing data from 4 patients using the Nanopore platform. The dataset is composed of 8 BAM files: 4 tumor samples and 4 paired blood samples.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-26T15:09:43.674167+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000511","title":"Comprehensive genomic characterization of early stage bladder cancer - whole exome sequencing data","description":"For this project about non-muscle invasive bladder cancer (NMIBC), we analysed WES data from 438 patients. The dataset is composed of 876 BAM files: 438 tumor samples and 438 paired blood samples.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-26T15:09:42.653844+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000512","title":"Comprehensive genomic characterization of early stage bladder cancer - Total RNA-seq data","description":"This study looks at the non muscle invasive bladder cancer subtypes based on totRNAseq data of 414 bladder cancer samples collected in different European centers within the UROMOL project. All samples were sequenced using paired reads on Illumina platforms. The reads are mapped to hg38. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-26T15:09:45.531954+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000513","title":"Comprehensive genomic characterization of early stage bladder cancer - shallow whole genome sequencing data","description":"For this project about non-muscle invasive bladder cancer (NMIBC), we analysed shallow WGS data from 362 patients. The dataset is composed of 392 BAM files: 362 tumor samples, 15 female normal samples and 15 male normal samples.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-26T15:09:44.595377+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000514","title":"cfDNA methylation profiling on longitudinally collected blood plasma of patients with esophageal adenocarcinoma ","description":"Esophageal adenocarcinoma (EAC) is an aggressive cancer characterized by a high risk of relapse post-surgery. Analyzing cell-free DNA (cfDNA) from blood plasma emerges as a promising avenue for therapy response monitoring. This study aims to evaluate the cost-effective and genome-wide cell-free reduced representation bisulfite sequencing (cfRRBS) method combined with computational deconvolution for effective disease monitoring in EAC patients.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-18T13:58:50.992429+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000515","title":"BulkRNAseq - Notch Signaling Maintains a Progenitor-Like Subclass of Hepatocellular Carcinoma","description":"To identify the Notch signaling components expressed in both the human cancer cells and mouse stromal cells that typically comprise PDX tumors, we performed bulk RNA sequencing. Our results demonstrate that a JAG1-NOTCH2 signaling axis within the human cancer cell population drives the Notch dependency in the super-responder models, with NOTCH2 serving as the functionally relevant receptor.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-04T10:24:38.770329+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000516","title":"ATACseq - Notch Signaling Maintains a Progenitor-Like Subclass of Hepatocellular Carcinoma","description":"To assess how Notch inhibition impacts chromatin accessibility and how chromatin changes relate to HNF4A and CEBPA activities, we performed Assay-for-Transposase-Accessible-Chromatin (ATAC) sequencing of LIV78 tumors, 72 hours after treatment with NOTCH2 blocking or control antibodies. Our TF activity and chromatin analyses thus lead to a model in which Notch inhibition leads to increased expression of CEBPA, thus enabling CEBPA to partner with HNF4A to jointly drive transcriptional programs and the underlying chromatin rearrangements that promote differentiation of progenitor-like tumor cells to a mature hepatocyte fate incompatible with tumor growth and maintenance.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-27T10:52:06.921864+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000517","title":"scRNAseq - Notch Signaling Maintains a Progenitor-Like Subclass of Hepatocellular Carcinoma","description":"To clarify the cellular composition and the mechanism of efficacy following JAG1/NOTCH2 inhibition, we performed single-cell sequencing of LIV78 tumors isolated from control animals or following inhibition of JAG1 or NOTCH2. The results suggest that sensitive tumors consist of heterogeneous populations of cells in distinct transcriptional states and that Notch signals emerge from ligand-receptor co-expressing cells.\r\n","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-04T10:24:41.873102+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000518","title":"ADARIO / Targeting ADAR1 in Immuno-Oncology","description":"RNA editing analyses of BRCA-isogenic cell lines and patient-derived xenografts (PDX)","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-06T15:33:13.172658+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000519","title":"Profiling of human fecal microbiota for succinate consumption","description":"The objective of this study was to identify the bacterial taxa responsible for succinate consumption in human gut microbiomes. We enriched fresh stool from healthy donors in growth medium with and without supplemented succinate. We then measured metabolite concentrations and bacterial composition in the stool and enrichment samples.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-27T09:29:51.609059+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000520","title":"Full characterization of structural variation ","description":"Structural variants (SVs) are important contributors to human disease. Their characterization remains however difficult due to their size and association with repetitive regions. Long-read sequencing (LRS) and optical genome mapping (OGM) can aid as their molecules span multiple kilobases and capture SVs in full. In this study, we selected six individuals who presented with unresolved SVs. We applied LRS onto all individuals and OGM to a subset of three complex cases. LRS detected and fully resolved the interrogated SV in all samples. This enabled a precise molecular diagnosis in two individuals. Overall, LRS identified 100% of the junctions at single-basepair level, providing valuable insights into their formation mechanisms without need for additional data sources. Application of OGM added straightforward variant phasing, aiding in the unravelment of complex rearrangements. These results highlight the potential of LRS and OGM as follow-up molecular tests for complete SV characterization. We show that they can assess clinically relevant structural variation at unprecedented resolution. Additionally, they detect (complex) cryptic rearrangements missed by conventional methods. This ultimately leads to an increased diagnostic yield, emphasizing their added benefit in a diagnostic setting. To aid their rapid adoption, we provide detailed laboratory and bioinformatics workflows in this manuscript. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-04T09:32:17.171787+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000521","title":"Testicular large B-cell lymphoma is genetically similar to PCNSL and distinct from nodal DLBCL","description":"Next generation sequencing (NGS) data analyzed in Rivas-Delgado, López, et al. HemaSphere 2024.\r\nSingle nucleotide variants (SNVs) and short insertions /deletions (indels) were evaluated in 42 samples using a B-cell malignancy-oriented targeted panel covering 115 genes (SureSelectXT, Agilent Technologies and sequenced in a MiSeq instrument (Illumina; 2x150bp; mean coverage of 599x). The NGS data of 39 samples is provided here. The 3 additional samples were previously published. Please, see the original publication for additional details.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000522","title":"Target sequencing for 53 synovial sarcoma patients","description":"This dataset contains 138 .bam files sequenced with Illumina NovaSeq 6000. The files with the variant calling performed to the sequencing data, as well as the clinical data (phenotype) extracted during the sample extraction. ","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-12T14:49:58.830594+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000523","title":"Genomic landscapes of endometrioid and mucinous ovarian cancers and morphologically similar tumor types","description":"While endometrioid and mucinous ovarian cancers represent nearly a quarter of ovarian cancers, their molecular characteristics and pathologic origins are poorly understood. To characterize the genomic and epigenomic alterations of these ovarian cancer subtypes and evaluate links to morphologically similar tumors from other sites, we performed sequence, copy number, mutation signature, rearrangement, and methylation analyses from tumor samples and matched normal tissues of 133 patients. These analyses included patients with ovarian endometrioid (n=44), ovarian mucinous (n=43), uterine endometrial (n=15), and gastrointestinal mucinous cancers (n=31). In addition to identifying genes previously known to be involved in these tumors, we identified alterations in RAD51C, NOTCH4, SMARCA1/4 and JAK1 in ovarian endometrioid, ESR1 in uterine endometrioid, and SMARCA4 in ovarian mucinous cancers. Whole genome sequencing revealed rearrangements involving PTEN, NF1, and NF2 in ovarian endometrioid tumors, and NF1 and MED1 in ovarian mucinous cancers. The number of alterations and affected genes in ovarian and uterine endometrioid cancers were similar as were genome-wide methylation profiles, suggesting that these tumors may have a similar tissue of origin. By contrast, methylation patterns in ovarian mucinous cancers were more similar to other gastrointestinal mucinous cancers, including mucinous cancers of the stomach, colon, and pancreas. These analyses provide insights into the genomic landscapes and origins of mucinous and endometrioid ovarian carcinomas, providing new avenues for early clinical intervention and management of patients with these cancers.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-30T16:09:03.86713+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000524","title":"Dynamics of Tumor Heterogeneity from Primary to Metastatic Dissemination in Prostate Cancer","description":"PRO-SPeCT: PROstate cancer heterogeneity deconvolution through Single cell Profiling of Chromatin accessibility and Transcriptomic output\r\nIdentifying drivers of cancer progression to guide treatment selection is hindered by limited abilities to understand tumor heterogeneity’s impact on evolution. Here, we delineated the phenotypic variability across ~300,000 prostate tumor cells collected from multiple loci in primary and matched locoregional metastases. We found inter-patient heterogeneity to be confined to malignant populations. While malignant cell populations exhibit intra-locus heterogeneity, they maintain inter-loci phenotypic similarity within a patient’s prostate gland. In addition, the intra-locus heterogeneity between malignant cell populations is paired with a common clonal architecture. Lastly, we show that malignant cell populations disseminating to locoregional lymph nodes mirror the clonal architecture and phenotypic heterogeneity observed across primary tumor loci while showcasing cell state transition toward inflammatory phenotypes. These findings provide insights into distinct measures of tumor heterogeneity, revealing diverse evolutionary paths across patients converging to common phenotypic adaptations in early prostate cancer progression.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-02T12:27:39.034362+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000525","title":"Identification of HER2-positive breast cancer molecular subtypes with potential clinical implications in the ALTTO clinical trial ","description":"In HER2-positive breast cancer, clinical outcome and sensitivity to HER2-targeted therapies are influenced by both tumor and microenvironment features. However, we are currently unable to depict the molecular heterogeneity of this disease with sufficient granularity. Here, by performing gene expression profiling in HER2-positive breast cancers from patients receiving adjuvant trastuzumab in the ALTTO clinical trial, we identified and characterized five molecular subtypes associated with the risk of distant recurrence: immune-enriched (IM), proliferative/metabolic-enriched (P/Met), mesenchymal/stroma-enriched (Mes/S), luminal (LUM), and ERBB2-enrichedERBB2-dependent (ERBB2-EERBB2-D). We next validated the biological profiles of the subtypes and explored their prognostic/predictive value in external cohorts, namely the NeoALTTO trial, SCAN-B, I-SPY2, METABRIC and TCGA. IM tumors presented better survival outcomes, in contrast to Mes/S and P/Met tumors, while LUM tumors and ERBB2-EERBB2-D were characterized by low and high rates of pathological complete response, respectively. Of note, these molecular subtypes provide the rationale for treatment approaches leveraging the heterogeneous biology of HER2-positive breast cancer.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-09T15:57:00.458758+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000526","title":"RNA-seq of murine osteosarcoma cell line genetically modified for CYR61","description":"Transcriptomic analysis of K7M2 murine osteosarcoma cells stably modified to overexpress or repress CYR61","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-11T15:11:41.428652+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000527","title":"Synergy study: \"Tissue resident CD8+ T cell clonal expansion in advanced triple negative breast cancer is associated with response to chemoimmunotherapy\"","description":"Dataset of 10x Genomics 5'prime single-cell RNA sequencing of 40 tumor biopsy samples or triple negative breast cancer. Samples are taken before and after immuno checkpoint blockade treatment. Processed according the 10X genomics protocol, sequenced on Immumina NovaSeq6000. Raw sequencing reads are further processed with Cellranger 3.0 to get gene-expression matrices.  ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-11T14:12:06.991211+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000528","title":"Single-cell RNA-seq and TCR-seq of synovial tissue and peripheral blood CD4+ and CD8+ T cells from patients with immune-mediated refractory arthritis","description":"In this study, we investigated CD4+ and CD8+ T lymphocytes from the synovial tissue and peripheral blood of patients with treatment-resistant immune-mediated arthritis using paired single-cell RNA and TCR-sequencing.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-12T14:55:57.744441+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000529","title":"Moroccan Genome Project: Sequencing Data from 109 Whole Genomes of Moroccan Individuals","description":"This study is the first phase of the Moroccan Genome Project, which included the complete sequencing of 109 genomes from the Kingdom of\r\nMorocco. The sequencing was performing using the Illumina NovaSeq6000 platform, with a mean coverage of 30X.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-04T10:46:18.932541+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000530","title":"Contribution of specific cell types to the development of Barrett’s esophagus and carcinoma via germline genetic risk","description":"This study was designed to elucidate how individual cell types in Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) contribute to disease development via germline genetic risk. We performed single cell RNA-sequencing (scRNA-seq) of BE, EAC and paired normal esophagus and gastric fundus tissue samples. After analyzing individual cell types, we integrated the scRNA-seq data and data of a genome-wide association study (GWAS) on BE/EAC to determine cell type-specific genetic risk. Raw data from the RNA-sequencing is provided here.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-18T14:40:22.313193+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000531","title":"Fecal microbiome predicts treatment response after the initiation of semaglutide or empagliflozin uptake","description":"To investigate the effect of semaglutide and empagliflozin initiation on the gut microbiome of type 2 diabetes patients. In addition, to analyze whether the pre-treatment gut microbiome can predict the treatment efficacy.\r\nGut microbiome fecal samples donated at four timepoints (Baseline, Month 1, Month 3; Month 12) were studied using 16S ribosomal RNA gene sequencing and analysis.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-26T13:39:41.296673+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000532","title":"Genotyping from targeted NGS data based on a small set of SNPs correctly matches patient samples","description":"Mislabelling and swapping of laboratory samples are handling errors that can lead to erroneous interpretation of data and/or patient harm. Sequenced samples can be traced back to the respective donors by matching of single nucleotide polymorphisms (SNPs). Here we used sequencing data (targeted NGS) from two cohorts of patients with chronic lymphocytic leukaemia to demonstrate the possibility of selecting informative SNPs from a typical targeted NGS panel and to create an automated workflow for detection of sample handling errors.","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-16T17:03:49.724304+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000533","title":"Characterisation of Cyr61-enriched myeloid angiogenic cells ","description":"We previously demonstrated the enrichment of an angiogenic precursor cell population from peripheral blood mononuclear cells by CYR61, a protein of the CCN family. In vivo, CYR61 mediates the binding of leukocytes and particular monocyte populations at sites of vascular inflammation. Here, we present an in vitro enrichment system mimicking (patho)physiology and at the same time representing an effective tool for enrichment of the CYR61-binding blood cells and analyzed this cell population in depth. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-23T16:48:08.583684+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000534","title":"Single-cell transcriptomic data of 9 DHG-H3G34 patient tumors.","description":"We applied single-cell/single-nucleus RNA-sequencing to a patient cohort of 9 fresh and frozen untreated diffuse hemispheric gliomas, H3G34-mutant (DHG-H3G34).","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-10T13:18:07.487464+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000535","title":"MEC/SEF rhabdomyosarcoma mRNA sequencing","description":"This project was undertaken to sequence and analyze mRNA expression in these tumor subtypes. We intended to discover distinctive patterns of tumor subtype gene expression in these subtypes. In addition, we used this data to discover expression differences between ESWR fusion positive and fusion negative MEC tumors.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-02T15:59:15.001238+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000536","title":"Base-excision repair pathway shapes 5-methylcytosine deamination signatures in pan-cancer genomes","description":"Transition of cytosine to thymine in CpG dinucleotides is the most frequent type of mutation in cancer. This increased mutability is commonly attributed to spontaneous deamination of 5-methylcytosine (5mC), which is normally repaired by the base-excision repair (BER) pathway. However, the contribution of 5mC deamination in the increasing diversity of cancer mutational signatures remains poorly explored. Here, we integrate mutational signatures analysis in a large series of tumor whole genomes with lineage-specific epigenomic data to draw a detailed view on 5mC deamination in cancer. We uncover tumor type-specific patterns of 5mC deamination signatures in CpG and non-CpG contexts. We demonstrate that the BER glycosylase MBD4 preferentially binds to open chromatin domains, which correlates with lower mutational burden in these domains. We validate our findings by modelling BER deficiencies in isogenic cell models. Overall, we establish MBD4 as the main actor responsible for 5mC deamination repair in humans.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-10T13:22:49.887923+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000537","title":"Scywalker: scalable end-to-end data analysis workflow for nanopore single-cell transcriptome sequencing","description":"Existing nanopore single-cell data analysis tools showed severe limitations in handling current data sizes. We developed novel scalable methods for cell barcode demultiplexing and single-cell isoform calling and quantification and incorporated these in an easily deployable package called scywalker.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-09T15:45:49.990872+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000538","title":"Duplex sequencing of selected breast cancer patients","description":"This study assessed the variant profiles of 22 samples from 11 breast cancer patients with adverse survival outcomes, including paired uninvolved mammary gland samples collected at various distances from primary lesions. Ultra-deep sequencing was performed to identify the presence of low-frequency pathogenic post-zygotic variants in PIK3CA and TP53 genes.","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-17T11:34:24.993605+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000539","title":"WES of breast cancer patients and controls","description":"This study assessed the variant profiles of 408 samples from 126 breast cancer patients with various survival outcomes, including paired uninvolved mammary gland samples collected at proximal distances from primary lesions. As a reference, control samples from 15 mammoplasty individuals without cancer history were studied. Whole exome sequencing was performed to identify post-zygotic and germline variants present in the studied samples. Variant annotation in known databases, interpretation, and statistical analyses followed to discern the clinical relevance of called variants.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-17T11:34:25.944245+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000540","title":"3D genome topology distinguishes molecular subgroups of medulloblastoma","description":"Medulloblastoma (MB) has four molecular subtypes, but their 3D genome architecture differences are unclear. We used in situ Hi-C on 28 surgical specimens and a patient-derived xenograft to reconstruct the 3D genome architecture of MB subtypes, finding that topologically associating domain (TAD) insulation scores could distinguish MB subtypes.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-10T10:43:37.520894+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000541","title":"Pipeline Olympics: Continuous benchmarking of computational workflows for DNA methylation sequencing data","description":"DNA methylation is a widely studied epigenetic mark and a powerful biomarker of cell type, age, environmental exposure, and disease. Genome-wide DNA methylation profiling is usually performed using whole-genome sequencing following selective conversion of unmethylated cytosines into thymines via bisulfite treatment or enzymatic methods. Numerous software tools facilitate processing of raw sequencing data for DNA methylation profiling, but a comprehensive benchmarking has been lacking. In this study, we systematically compared methods and tools for processing DNA methylation sequencing data. We established a dedicated benchmarking dataset comprising genome-wide DNA methylation profiling data for four reference samples using five experimental protocols each. The results of data processing were compared to highly quantitative locus-specific DNA methylation measurements available for 46 genomic loci. Based on this gold-standard reference dataset, we identified workflows that consistently demonstrated high performance. We present our results in an interactive application that provides a “living benchmark” ready for continuous updating as new workflows are proposed and require benchmarking against existing methods. In summary, our study provides guidance for any laboratory studying DNA methylation on a genome-wide scale.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-24T13:06:04.742179+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000542","title":"ICARUS-BREAST01-ExomeSeq","description":"Efficacy, safety and biomarker analysis of ICARUS-BREAST01: a phase 2 Study of Patritumab Deruxtecan in patients with HR+/HER2- advanced breast cancer. Whole-exome sequencing (WES) is available for 43 tumor samples and 43 blood samples collected at entry into the trial.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-08T12:41:55.703413+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000543","title":"ICARUS-BREAST01-RNAseq","description":"Efficacy, safety and biomarker analysis of ICARUS-BREAST01: a phase 2 Study of Patritumab Deruxtecan in patients with HR+/HER2- advanced breast cancer. RNA-squencing is available for 44 samples comprising 22 samples collected at entry into the trial and 22 samples collected during treatment (cycle 1 day 3, cycle 1 day 19, or cycle 2 day 3) from 22 patients.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-08T12:41:55.703413+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000544","title":"A clinically and genomically annotated Early onset colorectal cancer and late onset colorectal cancer   ","description":"This study aimed to identify genomic characteristics of early-onset colorectal cancer (EOCRC) compared to late-onset cases. Whole-genome sequencing (WGS) was performed on EOCRC and late-onset colorectal cancer (LOCRC) tissues and blood samples to analyze their genomic profiles.\r\n","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-30T08:10:54.331044+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000545","title":"Plasma cell‐Free transcriptome profiling in chronic liver disease","description":"Chronic liver disease (CLD) encompasses a wide range of hepatic disorders that progressively compromise liver function. In order to support the development of non-invasive diagnostic tools and improve patient stratification, we generated a high-throughput extracellular RNA sequencing dataset from blood plasma samples collected from patients at various stages of liver disease. Samples were obtained from two independent cohorts of 112 (cohort 1) and 489 (cohort 2) patients using standardized collection and processing protocols, and profiled using total RNA sequencing (SMARTer Stranded Total RNA-Seq Kit v3 - Pico Input Mammalian), resulting in 112 and 820 extracellular transcriptomic profiles for cohort 1 and 2, respectively. This dataset is provided with full documentation of the preprocessing analysis pipeline and accompanying metadata, enabling its use as an independent validation cohort for biomarker discovery and as a complementary resource for integrative multi-omics studies, even in cases with incomplete data modalities. The publicly available resource is intended to facilitate reproducibility and foster further research in the field of liver disease diagnostics","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-10T11:26:36.218524+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000546","title":"Multiple myeloma treated with T-cell redirecting immunotherapies","description":"Whole Genome Sequencing from patients with multiple myeloma treated with T-Cell redirecting therapies including chimeric antigen receptor T-cells (CAR-T) and Bispecific T-cell Engagers (TCE).","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-04T10:59:21.238131+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000547","title":"Single cell RNA and ATAC sequencing data from GBM patients","description":"Glioblastoma cells infiltrate and incorporate into the normal brain parenchyma. We conduct unbiased multimodal single-cell and spatial sequencing to capture GBM cells and the surrounding tumor microenvironment using a regional sampling strategy. For each patient, we profile the peritumoral region, tumor edge, and tumor core, providing a comprehensive characterization of the transcriptional and epigenetic landscape of GBM spatial heterogeneity, with a specific focus on infiltrative cells.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-12T10:01:48.357055+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000548","title":"Screening for tryptophan conversion in human stool samples","description":"The goal of this study was to compare the tryptophan metabolism of different human fecal microbiota. To this end we enriched human stool samples in culture medium and measured growth and metabolite concentrations after 48h of culture. We quantified the consumption of tryptophan and the production of typical tryptophan derivaties.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000549","title":"Stratified Medicine Paediatrics (SMPaeds): molecular profiling of relapsed paediatric cancer","description":"We profiled a large heterogenous cohort of matched diagnostic-relapse tumour tissue and plasma-derived cell free DNA (cfDNA) from patients with relapsed and progressive solid tumours of childhood. Tumour DNA and cfDNA were analysed by targeted panel sequencing and low coverage whole genome sequencing.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-14T11:41:33.918269+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000550","title":"Ultra-sensitive ctDNA monitoring required for predicting response and resistance to immunotherapy in advanced melanoma","description":"Circulating tumor DNA (ctDNA) monitoring in peripheral blood has shown promise for disease surveillance and prognostication of ICI response. Yet even in the metastatic context, ctDNA signals can be missed, suggesting the need for increased assay sensitivity. We used a tumor-informed ctDNA assay capable of detection down to 1 part-per-million (PPM) ctDNA to profile 188 plasma samples from 23 melanoma patients receiving ICI over several years.  Residual disease was detected in ctDNA over a broad range, from 130,000 PPM down to 2.3 PPM, with approximately a quarter of detections below 50 PPM. Early on-treatment increases in ctDNA level, and both ctDNA-based molecular clearance (mCR) and molecular progression (mPD) were all prognostic of both OS and PFS. Additionally, mCR consistently preceded radiographic imaging. Our results show the importance and utility of an ultra-sensitive ctDNA assay in advanced melanoma treated by ICI with potential implications for other cancers. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-30T12:56:14.051173+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000551","title":"test","description":"test","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000552","title":"Nanopore whole genome sequencing data of HG002 ","description":"Data generated from single cell, 10 cells, and bulk samples of HG002.\r\n\r\n","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-18T14:54:45.880974+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000553","title":"Nanopore whole genome sequencing data of human PGT samples","description":"Data generated from embryo trophectoderm biopsies and corresponding parental blood samples","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-18T14:54:45.880974+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000554","title":"Genomic Profile of Multiple Localised Spiradenoma and Spiradenocarcinoma","description":"Multiple spiradenomas and spiradenocarcinoma from a single donor were subjected to exome sequencing. Tumor samples were microdissected from formalin-fixed, paraffin-embedded tissue, and genomic DNA was extracted. The DNA samples were subjected to library generation using the xGen ssDNA & Low-Input DNA Library Preparation Kit, followed by exome capture using the xGen Exome Research Panel v2. The libraries were sequenced on DNBSEQ G400RS. Reads were aligned to GRCh37 with BWA.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-25T13:52:09.642127+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000555","title":"bulk mRNA-seq of iGRAN (CD14neg) cells from CMML patients and healthy donors","description":"bulk mRNA-seq of iGRAN (CD14neg) cells from CMML patients and healthy donors\r\n\r\n[Publication title] CXCL8 secreted by immature granulocytes inhibits wildtype hematopoiesis in chronic myelomonocytic leukemia","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-28T11:14:27.760774+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000556","title":"Single-cell RNA-seq of PBMC from 2 patients iGRAN-Low and 2 patients iGRAN-High","description":"Single-cell RNA-seq of PBMC from 2 patients iGRAN-Low and 2 patients iGRAN-High\r\n\r\n[Publication title] CXCL8 secreted by immature granulocytes inhibits wildtype hematopoiesis in chronic myelomonocytic leukemia","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-28T11:14:27.760774+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000557","title":"Exome-sequencing from monocytes (CD14pos), T-lymphocytes (CD3pos) and iGRAN (CD14neg) cells from CMML patients","description":"Exome-sequencing from monocytes (CD14pos), T-lymphocytes (CD3pos) and iGRAN (CD14neg) cells from CMML patients\r\n\r\n[Publication title] CXCL8 secreted by immature granulocytes inhibits wildtype hematopoiesis in chronic myelomonocytic leukemia","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-28T11:14:27.760774+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000558","title":"Characterization of copy number quiet oral cancer","description":"Copy number quiet head and neck squamous cell carcinoma are a distinct subset with relatively good prognosis. Previous work has indicated this subset is most commonly found in the oral cavity and is highly enriched for HRAS and CASP8 mutations. TP53 mutations are much less common than in CNA-quiet oral cancers. In this study we corroborate the validity of CNA-quiet tumors as a distinct subset in a large OSCC cohort and further chart clinical, genomic, and immunological characteristics of this subset.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[39428388],"external_links":null,"is_released":true,"released_date":"2024-09-16T09:40:08.115832+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000559","title":"Rapid brain tumor classification from sparse epigenomic data","description":"Although the intraoperative, molecular differential diagnosis of the approximately one hundred different brain tumor entities described to date has been a goal of neuropathology in the last decade, this has not yet been achieved in a clinically relevant time frame of less than one hour after biopsy collection. Recent advances in third-generation sequencing technologies have brought this once-elusive goal within reach. However, established machine learning techniques rely on concepts and methods, impractical for live diagnostic workflows in clinical applications. Here, we present MethyLYZR, a Naïve Bayesian framework enabling fully tractable live classification of cancer epigenomes. MethyLYZR can be run in parallel with an ongoing Nanopore experiment with negligible computational cost and provides clinically relevant and accurate cancer classification results within 15 minutes of sequencing. Therefore, only the time required for DNA extraction and the Nanopore sequencer's maximum parallel throughput remain limiting factors for even faster time-to-results. We demonstrate the potential utility of the MethyLYZR framework not only for the neurosurgical intraoperative use case but also for other oncologic indications and cell-free DNA from liquid biopsies.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-23T16:29:13.24429+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000560","title":"Cancer cell and tumor microenvironment biomarkers associated with disease-free survival with adjuvant nivolumab in the phase 3 CheckMate 274 trial","description":"In the CheckMate 274 trial, adjuvant nivolumab versus placebo demonstrated an improvement in the primary endpoint of disease-free survival (DFS) in patients with high-risk muscle-invasive urothelial carcinoma after radical resection. An extensive analysis of tumor biomarkers, including their associations with DFS, was performed. Analysis of genome-wide differential gene expression and known gene signatures found that immune-related genes and pathways, in particular an IFNγ signature, were predictive of DFS in nivolumab-treated patients. Predictive and prognostic associations, respectively, were found for tumor-infiltrating CD4 and CD8 T cells. Analysis of a composite predictive model suggested that CD4 gene expression and tumor cell PD-L1 expression had the greatest contributions to predicting outcomes in nivolumab-treated patients. These results reinforce recent studies establishing the importance of biomarkers of adaptive immunity, and in particular CD4 T cells, in influencing response to PD-1/PD-L1 blockade and establish the potential predictive rather than solely prognostic nature of such findings. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-19T12:26:37.697934+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000561","title":"Divergent WNT Signaling and Drug Sensitivity Profiles within Hepatoblastoma Tumors and Organoids","description":"Hepatoblastoma, the most prevalent pediatric liver cancer, almost always carries a WNT-activating CTNNB1 mutation, yet exhibits notable molecular heterogeneity. To characterize this heterogeneity and identify novel targeted therapies, we perform comprehensive analysis of hepatoblastomas and tumor-derived organoids using single-cell RNA-seq/ATAC-seq, spatial transcriptomics, and high-throughput drug profiling. We identify two distinct tumor epithelial signatures: hepatic ‘fetal’ and WNT-high ‘embryonal’, displaying divergent WNT signaling patterns. The fetal group is enriched for liver-specific WNT targets, while the embryonal group is enriched in canonical WNT target genes.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-16T11:50:24.642375+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000562","title":"Rapid brain tumor classification from sparse epigenomic data","description":"Although the intraoperative, molecular differential diagnosis of the approximately one hundred different brain tumor entities described to date has been a goal of neuropathology in the last decade, this has not yet been achieved in a clinically relevant time frame of less than one hour after biopsy collection. Recent advances in third-generation sequencing technologies have brought this once-elusive goal within reach. However, established machine learning techniques rely on concepts and methods, impractical for live diagnostic workflows in clinical applications. Here, we present MethyLYZR, a Naïve Bayesian framework enabling fully tractable live classification of cancer epigenomes. MethyLYZR can be run in parallel with an ongoing Nanopore experiment with negligible computational cost and provides clinically relevant and accurate cancer classification results within 15 minutes of sequencing. Therefore, only the time required for DNA extraction and the Nanopore sequencer's maximum parallel throughput remain limiting factors for even faster time-to-results. We demonstrate the potential utility of the MethyLYZR framework not only for the neurosurgical intraoperative use case but also for other oncologic indications and cell-free DNA from liquid biopsies.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000563","title":"Identification and characterization of tertiary lymphoid structures in brain metastases","description":"Brain metastases (BrM) are the most common cancers in the brain. We performed transcriptome-wide gene expression profiling combined with spatial immune cell profiling to characterize the tumor immune microenvironment in BrM from different primary tumors. We found that BrM from lung carcinoma and malignant melanoma showed overall higher immune cell infiltration as compared to BrM from breast carcinoma. RNA sequencing-based immune cell deconvolution revealed gene expression signatures indicative of tertiary lymphoid structures (TLS) in subsets of BrM from lung cancer and melanoma. This finding was corroborated by multiplex immunofluorescence staining of immune cells in BrM tissue sections. Detection of TLS signatures was associated with prolonged survival after BrM diagnosis in lung cancer patients. Our findings highlight the cellular diversity of the tumor immune microenvironment in BrM of different cancer types and suggest a role of TLS formation for BrM patient outcome.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-16T13:16:32.326273+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000564","title":"Large B cell lymphomas with CCND1 rearrangement have different immunoglobulin gene breakpoints and genomic profile than mantle cell lymphoma","description":"Next-generation sequencig data including whole-genome sequencing, whole-exome sequencing, and capture-based gene panels of large B cell lymphomas with CCND1 rearrangementas described in Özoğul,Montaner, Pol et al 2024.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-25T09:39:49.731082+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000565","title":"Whole-Exome Sequencing Plasma Control Samples for Benchmarking","description":"This study contains whole-exome sequencing plasma and HapMap (12877, 12878) control samples for bioinfomatic bencmarking. Plasma samples contain variations in the genes KRAS, NRAS, PIK3CA, and EGFR, including insertions and deletions, at 0.0%, 0.1%, 1.0%, and 5.0%.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-16T17:17:36.419419+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000566","title":"Characterizing the cell-free transcriptome in a humanized DLBCL patient-derived tumor xenograft model for RNA-based liquid biopsy in a preclinical setting","description":"This study explores the cell-free transcriptome in a humanized DLBCL patient-derived tumor xenograft (PDTX) model. Blood plasma samples (n=171) derived from a DLBCL PDTX model including 27 humanized (HIS) PDTX, 8 HIS non-PDTX and 21 non-HIS PDTX NOD-scid IL2Rgnull mice were collected during humanization, xenografting, treatment, and sacrifice. The mice were treated with either R-CHOP, huCD20-Fc-AFN-CHOP, or phosphate-buffered saline (PBS). RNA was extracted using the miRNeasy serum/plasma kit and sequenced on the NovaSeq 6000 platform using the SMARTer Stranded Total RNA-seq pico v3 kit. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-16T17:22:15.839971+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000567","title":"Neoadjuvant nivolumab or nivolumab plus ipilimumab in early-stage triple negative breast cancer: phase 2 adaptive BELLINI trial. RNA-Seq","description":"The adaptive BELLINI trial explored whether short combination ICI induces immune activation (primary endpoint: two-fold increase in CD8+ T cells or IFNG), providing rationale for neoadjuvant ICI without chemotherapy. In window of opportunity cohorts A (4 weeks anti-PD1) and B (4 weeks anti-PD1 + anti-CTLA4), we observed immune activation in 53% (8/15) and 60% (9/15) of patients, respectively. High tumor-infiltrating lymphocytes (TILs) correlated with response. Based on these data, we opened cohort C for patients with high TILs (≥50%) who received 6 weeks neoadjuvant anti-PD1 + anti-CTLA4 followed by surgery (primary endpoint: pathological complete response, pCR). 53% (8/15) of patients had major pathological response (< 10% viable tumor) at resection, with 33% (5/15) having pCR. All cohorts met Simon’s two-stage threshold for expansion to stage II. In conclusion, neoadjuvant immunotherapy without chemotherapy demonstrates potential efficacy and warrants further investigation in patients with early TNBC. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-16T09:35:58.270021+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000568","title":"Neoadjuvant nivolumab or nivolumab plus ipilimumab in early-stage triple negative breast cancer: phase 2 adaptive BELLINI trial. WES","description":"The adaptive BELLINI trial explored whether short combination ICI induces immune activation (primary endpoint: two-fold increase in CD8+ T cells or IFNG), providing rationale for neoadjuvant ICI without chemotherapy. In window of opportunity cohorts A (4 weeks anti-PD1) and B (4 weeks anti-PD1 + anti-CTLA4), we observed immune activation in 53% (8/15) and 60% (9/15) of patients, respectively. High tumor-infiltrating lymphocytes (TILs) correlated with response. Based on these data, we opened cohort C for patients with high TILs (≥50%) who received 6 weeks neoadjuvant anti-PD1 + anti-CTLA4 followed by surgery (primary endpoint: pathological complete response, pCR). 53% (8/15) of patients had major pathological response (< 10% viable tumor) at resection, with 33% (5/15) having pCR. All cohorts met Simon’s two-stage threshold for expansion to stage II. In conclusion, neoadjuvant immunotherapy without chemotherapy demonstrates potential efficacy and warrants further investigation in patients with early TNBC. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-16T09:35:59.310253+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000569","title":"Whole-genome sequencing of BRCA-mutant breast cancer patient samples from tumour, germline tissue and plasma","description":"The use of circulating tumor DNA (ctDNA) to profile mutational signatures presents a non-invasive opportunity for understanding cancer mutational processes. In this study we developed MisMatchFinder, a liquid biopsy approach for mutational signature detection using low-\r\ncoverage whole-genome sequencing of ctDNA. Through analysis of plasma samples across multiple different cancers, we demonstrated that MisMatchFinder accurately infers single-base and doublet-base substitutions as well as indels to enhance detection of ctDNA and clinically relevant mutational signatures.\r\n\r\nThis study contains fastq files from whole-genome sequencing of temporally matched tumour (fresh frozen biopsies), blood germline and plasma samples collected from a BRCA1-mutant breast cancer patient to directly compare mutation signature analysis using gold-standard tumour-germline paired variant calling with our novel ctDNA-based method (MisMatchFinder). \r\n","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-17T12:48:12.68016+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000570","title":"Repeat expansions with small TTTCA insertions in MARCHF6 cause Familial Adult Myoclonus without Epilepsy","description":"Familial Adult Myoclonic Epilepsy (FAME) is a rare autosomal dominant disorder characterized by cortical tremulous myoclonus and generalized tonic clonic (GTCS) or myoclonic seizures. Intrafamilial variability regarding the prevalence of seizure has been reported. Despite apparent genetic heterogeneity, FAME is caused by the same TTTTA/TTTCA pentanucleotide repeat expansion in introns of seven different genes with no common function. Expansions containing only TTTTA repeats are benign, and only expansions including a TTTCA expansion insertion, which can be located 3' to the TTTTA expansion or in the middle of the TTTTA repeats, are pathogenic. We aimed to identify the underlying genetic cause of dominant cortical myoclonus without GTCS in two unrelated families. We used a combination of repeat-primed PCR, long-range PCR and nanopore sequencing to detect and characterize expansions at known FAME loci. We report a novel configuration of the FAME3 repeat expansion in MARCHF6 segregating with cortical myoclonus without epilepsy GTCS in both families. This expansion predominantly comprises elongated TTTTA repeats, ranging from 388 to 454 repeats, with the presence of only 5-11 TTTCA repeats at its 3' terminus (i.e., 5’-(TTTTA)~388-454(TTTCA)5-11-3’). This configuration exhibits greater stability upon meiotic transmission but somatic variability in TTTCA repeat number was detected at low level in blood. We observed an inverse correlation between the number of TTTCA repeats and the age at myoclonus onset. This study shows that as little as five TTTCA juxtaposed with expanded TTTTA expansions is sufficient to cause cortical myoclonus without GTCS. This finding has implications regarding possible pathophysiological mechanisms leading to FAME.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-17T12:51:56.576293+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000571","title":"Spatiotemporal single-cell roadmap of human skin wound healing","description":"Wound healing is vital for human health, yet the details of cellular dynamics and coordination in human wound repair remain largely unexplored. To address this, we conducted single-cell and spatial transcriptomics analyses on human skin and acute wound tissues through inflammation, proliferation, and remodeling phases of wound repair from the same individuals, monitoring the cellular and molecular dynamics of human skin wound healing at an unprecedented spatiotemporal resolution. Comparison with single-cell data from venous and diabetic foot ulcers uncovers a link between failed keratinocyte migration and impaired inflammatory response in chronic wounds.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-23T11:12:43.411225+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000572","title":"Helmsley sequencing data - scRNAseq - IBD - Nathalie Stakenborg - A Macrophage Atlas of the Human Gut","description":"We aimed to study the difference in macrophage clusters in each layer of the gut (namely mucosa, submucosa and muscularis) between IBD patients and control human samples. Thus, we created a Macrophage Atlas of the Human Gut in each layer separately and for control patients and IBD ones. For this purpose, we sequenced single cells of 37 samples. We could then compare the abundance and transcription profiles of macrophage clusters between layers and the switches arising with IBD, an inflammation of the gut. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000573","title":"A prospective trial comparing adaptive long-read sequencing and short-read genome sequencing for genetic diagnosis of cerebellar ataxia","description":"This study evaluated the effectiveness of long- and short-read sequencing as diagnostic tools for CA. We recruited 110 individuals (48 females, 62 males) with a clinical diagnosis of CA. Short-read genome sequencing (SR-GS) was performed to identify pathogenic RE and also non-RE variants in 356 genes associated with CA. Long-read adaptive sequencing (LR-AS) was performed to identify pathogenic RE in 67 genes.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-26T15:07:04.568037+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000574","title":"Inhibition of Cbl-b restores effector functions of human intratumoral NK cells","description":"This study investigates the efficacy of a Cbl-b inhibitor compound in enhancing and reinvigorating the activity of human dysfunctional NK cells.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-22T13:24:26.585012+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000575","title":"TDP43 proteinopathy leads to divergent cryptic splicing in the cortex and spinal cord","description":"Mislocalization of the nuclear TAR DNA-binding protein 43 (TDP43) is a hallmark of ALS and FTD which leads to de-repression and inclusion of cryptic exons, promising biomarkers of TDP43 pathology in a spectrum of neurodegenerative diseases. However, most cryptic exons to date have been identified from in vitro models or a single cortical FTD dataset, and little is known about cryptic splicing in the spinal cord, or within different neuronal subtypes. We meta-analyzed published bulk RNAseq datasets representing 1,778 RNAseq profiles of ALS and FTD post-mortem tissue, and in vitro models with experimentally depleted TDP43. We identified 142 cryptic splices, including 76 novel events. We found a novel pattern of spinal cord cryptic splicing, validated in an independent cohort by qPCR, which differed significantly from cortical and in vitro splicing. Finally, leveraging multiple public single-nucleus RNAseq datasets of ALS and FTD motor and frontal cortex, we confirmed the elevation of cortical-enriched splices in disease and localized them to layer-specific neuronal populations. This catalog of cryptic splices could inform efforts to develop biomarkers for tissue-specific and cell type-specific TDP43 pathology.\r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-15T10:32:56.115885+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000576","title":"A methylation and hydroxymethylation atlas of normal and tumour tissues ","description":"DNA cytosine modifications, 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are key epigenetic regulators of gene expression. Here, we present the first human atlas containing matched 5mC and 5hmC signatures for 13 normal tissue types, 9 blood cell types, 2 pre-cancerous tissue types, and 10 types of common solid tumours, profiled using our unique sequencing techniques, TAPSβ and CAPS+. This atlas contains whole-genome, base-resolution, quantitative 5mC and 5hmC information for 116 samples, at a mean coverage of 30×.  cfDNA samples were also included in this study, including samples processed using both cfTAPS and cfCAPS+","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000577","title":"Tumor Profiler AML Study","description":"Multi-omics data generated from 22 samples from the Tumor Profiler AML cohort","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-25T13:49:50.155834+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000578","title":"Genetic analysis of short stature using whole exome sequencing","description":"The aim of the study is to find the genetic aetiologies of short stature, using whole-exome sequencing technology.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-30T15:49:53.951489+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000579","title":"IL-17B uses IL-17RA and IL-17RB to induce Type-2 inflammation from human lymphocytes","description":"IL-17 family cytokines are critical to host defense responses at cutaneous and mucosal surfaces. Whereas IL-17A, IL-17F, and IL-17C induce overlapping inflammatory cascades to promote neutrophil-mediated immunity, IL-17E/IL-25 drives type 2 immune pathways and eosinophil activity. Genetic and pharmacological studies reveal the significant contribution these cytokines play in antimicrobial and autoimmune mechanisms. However, little is known about the related family member, IL-17B, with contrasting reports of both pro- and anti-inflammatory function in rodents. We demonstrate that in the human immune system, IL-17B is functionally similar to IL-25 and elicits type 2 cytokine secretion from innate type 2 lymphocytes, NKT, and CD4+ CRTH2+ Th2 cells. Like IL-25, this activity is dependent on the IL-17RA and IL-17RB receptor subunits. Furthermore, IL-17B can augment IL-33–driven type 2 responses. These data position IL-17B as a novel component in the regulation of human type 2 immunity.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-18T09:31:01.015774+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000580","title":"Single-cell targeted DNA-sequencing and protein sequencing","description":"We performed single-cell targeted DNA sequencing (MissionBio) on 13 high hyperdiploid B-ALL patients at diagnosis to study the genetic heterogeneity. For a number of patients single-cell surface protein antibody sequencing was added (DAB-seq) to better characterize the different cell types. Furthermore, additional samples during treatment were collected and analysed for some patients. In this way we want to study the clonal heterogeneity of these B-ALL samples, based both on mutations and CNVs, and identify resistant clones that could be targeted after relapse.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-07T09:56:17.113458+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000581","title":"Comparison of  healthy, compensated-, or decompensated cirrhosis ","description":"Study of  healthy, compensated-, or decompensated cirrhosis on samples of the human duodenal pinch biopsies taken during gastroscopy (D2 region) by single-cell sequencing.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000582","title":"Longitudinal single-cell transcriptomic study in patient-derived xenografts of pediatric T-ALL","description":"In this study, we conducted single cell full length total RNA sequencing (VASA-seq) on 13 matched pediatric T-ALL PDX samples at initial diagnosis and relapse, along with 5 non-relapsing PDX samples collected at initial diagnosis. We identified a subpopulation of T-ALL cells with stem-like cell features that expands substantially at relapse indicating resistance to first-line therapy. Chemotherapy resistance was further validated through functional testing: Two samples were subjected to in-vitro drug testing, treated with Cytarabine for three days, followed by single-cell transcriptomic analysis using 10x Genomics. Additionally, in-vivo drug testing was conducted on one sample, involving re-engraftment into mice and treatment with a combination of Vincristine, Doxorubicin, and Dexamethasone. Single-cell transcriptomic analysis using 10x Genomics was performed after 0, 15 and 30 days of treatment.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-23T16:49:24.770098+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000583","title":"Rapid brain tumor classification from sparse epigenomic data","description":"Although the intraoperative, molecular differential diagnosis of the approximately one hundred different brain tumor entities described to date has been a goal of neuropathology in the last decade, this has not yet been achieved in a clinically relevant time frame of less than one hour after biopsy collection. Recent advances in third-generation sequencing technologies have brought this once-elusive goal within reach. However, established machine learning techniques rely on concepts and methods, impractical for live diagnostic workflows in clinical applications. Here, we present MethyLYZR, a Naïve Bayesian framework enabling fully tractable live classification of cancer epigenomes. MethyLYZR can be run in parallel with an ongoing Nanopore experiment with negligible computational cost and provides clinically relevant and accurate cancer classification results within 15 minutes of sequencing. Therefore, only the time required for DNA extraction and the Nanopore sequencer's maximum parallel throughput remain limiting factors for even faster time-to-results. We demonstrate the potential utility of the MethyLYZR framework not only for the neurosurgical intraoperative use case but also for other oncologic indications and cell-free DNA from liquid biopsies.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000584","title":"Recurrent CLTC::SYK fusions and CSF1R mutations in juvenile xanthogranuloma of soft tissue","description":"In this study, the genomic landscape of extracutaneous juvenile xanthogranuloma (JXG) was analyzed. By leveraging the Dutch Nationwide Pathology Databank (Palga), tumor samples were obtained from different academic medical centers in the Netherlands. The study was approved by the Palga Scientific Council and Privacy Committee (LZV-2016-183) and the Institutional Review Board of Leiden University Medical Center (B19.074). In addition, the study was approved by the Biobank and Data Access Committee of the Princess Máxima Center for Pediatric Oncology (PMCLAB2024.0512).\r\n\r\nProvided are whole transcriptome sequencing (WTS) data of 3 histiocytic tumors with CLTC::SYK fusions.\r\n\r\nWTS was performed in the routine workflow of the Princess Máxima Center for Pediatric Oncology (as described in Hehir-Kwa, et al. JCO Precis Oncol 2022). RNA was derived from formalin-fixed paraffin-embedded tumor tissue (n=1) or from frozen tumor tissue (n=2).","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-07T09:56:35.737999+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000585","title":"Single-nucleus RNA-sequencing of normal adrenal cortex and adrenocortical tumors","description":"This study reports a single-nucleus transcriptome atlas of steroid, stromal and immune cells in 38 human normal adrenals and adrenocortical tumors.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-29T16:00:56.326894+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000586","title":"Genome sequencing identifies splice-disrupting variants in childhood heart disease","description":"We used genome sequencing (GS) to identify cardiac specific splice disrupting variants that were subsequently validated in a subset of participants. In turn, we developed a heart-specific model for canonical and non-canonical splice variants, which was applied to patients with congenital heart disease (CHD). These included patients with two of the most common forms of cyanotic CHD i.e. tetralogy of Fallot (TOF) and dextro-transposition of the great arteries (TGA). In addition to identifying canonical splice-disrupting variants in known CHD-related genes in 1% cases, this approach identified putatively damaging non-canonical splice-disrupting variants in 11% of isolated CHD, with deeply intronic variants representing 53% of non-canonical splice-disrupting variants in CHD genes. GS was critical for the identification of variants that would not be captured by routine clinical genetic tests including exome sequencing, while cardiac RNA-Seq allowed for high specificity in the interpretation of splice-disrupting effects in the heart. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-25T13:50:46.398266+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000587","title":"Variables of diversity, clonality, V and J usage and main COVID-19-reactive GLIPH2 frequencies.","description":"Main results of the T cell repertorie analysis of a cohort of 61 patients. For each patient, repertorie diversity and clonality metrics, V an J alelle frequency and COVID-19-reactive sequencies have been calculated using open.source code. For more information about the study, please visit  DOI: 10.1186/s40246-024-00654-0","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[39227859],"external_links":null,"is_released":true,"released_date":"2024-09-23T15:53:14.362524+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000588","title":"Variables of mass cytometry (CyTOF) innate immune cell counts ","description":"For 61 COVID-19 patients we performed a CyTOF analysis to characterize the innate immune landscape associated with disesase severity. For this study, 37 analyzed populations have been included, speccialy focused in monocyte-macrophague subpopulations. For more information, please consult DOI: 10.3389/fimmu.2022.1094644","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[36969980],"external_links":null,"is_released":true,"released_date":"2024-09-23T15:53:14.362524+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000589","title":"Genotype variables of the 61 COVID-19 patient cohort used in the main project of data integration","description":"We selected SNPs with a minor allele frequency (MAF) higher than 10% in the Caucasian population from the Ensembl database. Specifically, we selected ACE2 (rs2285666), MX1 (rs469390), and TMPRSS2 (rs2070788) for the present analysis. For more information, please refer to: ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[37287057],"external_links":null,"is_released":true,"released_date":"2024-09-23T15:53:14.362524+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000590","title":"Circulating immune cell landscape in colorectal cancer patients","description":"To understand the circulating immune cells in colorectal cancer patients, we performed single-cell RNA sequencing for 14 PBMC samples from 14 colorectal cancer patients. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-30T17:18:15.778464+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000591","title":"Whole-exome sequencing identifies new pathogenic germline variants in patients with colorectal polyposis","description":"Adenomatous polyposis confers an increased risk of colorectal cancer development. Here, we investigated probably underlying predisposition variants in patients with suspected colorectal polyposis without variants in APC and MUTYH genes by whole exome sequencing (WES). Twenty-seven patients were included and subjected to germline WES. After filtering out variants for sequencing quality, variant allele fraction frequency, and population frequency, variants were manually prioritized by the ACMG criteria. Among the variants identified, 17 were classified as pathogenic or likely pathogenic (in 12 patients). This study gives information of probably associated polyposis variants in Brazilian patients without germline pathogenic variants in APC and MUTYH genes, supporting the utilization of next-generation sequencing for screening in these patients beyond these genes.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-09-23T10:57:26.901013+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000592","title":"Multidimensional Proteomics analysis of intractable cancers with prospective observational cohort for precision medicine","description":"Multi-omics project of Non small cell Lung Cancer. Exome and RNAseq datasets were generated from normal-tumor pairs of Non small cell Lung Cancer patients from the retrospective cohort.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-31T12:52:24.233195+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000593","title":"Ex vivo modeling of precision immuno-oncology responses in lung cancer","description":"Single-cell RNA-sequencing (scRNA-seq) data from paired lung cancer organoids and immune cells. The experiment was performed using the Single Cell 5' solution of 10X Genomics.  The dataset includes 15 samples from 4 multiplexed experiments. The multiplexing was performed using the Feature Barcoding technology of 10X Genomics.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-21T12:03:26.568138+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000594","title":"Transcriptome analysis of leiomyosarcoma","description":"We performed transcriptome analysis of leiomyosarcoma","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-15T17:25:59.111085+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000595","title":"Targeted gene panel sequencing of leiomyosarcoma","description":"We conducted MSK-IMPACT sequencing of leiomyosarcoma.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-15T17:25:59.111085+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000596","title":"Cas9-targeted-based long-read sequencing for genetic screening of RPE65 locus","description":"In order to compare sequencing performance of different technologies in a specific locus, we sequenced blood samples of five inherited retinal dystrophies (IRD) patients harboring a monoallelic variant in RPE65 that remained uncharacterized with: 1) Clinical exome targeted sequencing (CES), 2) whole genome sequencing (WGS), and 3) Long-read sequencing on a MinION platform where CRISPR-Cas9 guide RNA probes were designed to target a 31 kb region including the entire RPE65 locus.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-08T10:23:37.316953+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000597","title":"Genetic alterations as a mechanism for modulating response to target therapy in Head and Neck Squamous Cell Carcinoma (HNSCC)","description":"Considering that EGFR inhibitors are the only target therapy approved by the FDA\r\nfor Head and Neck Squamous Cell Carcinoma (HNSCC) treatment and that to date there are no\r\npredictive markers of resistance, analyses based on the response profile to these inhibitors in\r\ncombination with pathological diagnosis would be useful for predicting the behavior of these\r\ntumors, and thus better classifying patients into distinct subgroups. Therapies targeting the\r\ninhibition of EGFR, VEGFR, and proteasomes are potential new approaches to cancer treatment\r\nand the modulation of methylation in the response may allow for a better selection of patients\r\npotentially sensitive to these drugs and for the development of new therapeutic strategies to\r\novercome this resistance. This project aimed to deepen our knowledge of cellular sensitivity and\r\nresistance to EGFR, VEGFR, and proteasome inhibitors in HNSCC, and to investigate the\r\npotential role of genetic alterations in modulating this response.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000598","title":"RNA-seq of CRC patient-derived xenograft tumors","description":"We developed a novel antibody-drug conjugate (ADC), 84-EBET. To analyze mechanism of action of 84-EBET, we obtained bulk RNA-seq data of the patient-derived xenograft (PDX) model derived from colorectal cancer (CRC) patient. The PDX model was treated with 5-fluorouracil + oxaliplatin, 84-EBET or vehicle, and then gene expression changes were analyzed with bulk RNA-seq.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-07T18:20:02.000799+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000599","title":"Tumor Profiler Melanoma Study","description":"The Tumor Profiler Study is an observational trial combining a prospective diagnostic approach to assess the relevance of in-depth tumor profiling to support clinical decision-making with an exploratory approach to improve the biological understanding of the disease. Technologies used are digital pathology, targeted NGS, single-cell RNA, single-cell DNA, bulk RNA, bulk proteotyping, single-cell CyTOF, imaging mass cytometry, pharmacoscopy, 4i Drug Response Profiling, and cell-free DNA.\r\nThese technologies were applied to 240 tumor samples collected over 3 years across three cancer indications: metastatic melanoma, metastatic epithelial ovarian cancer, and acute myeloid leukemia (AML).\r\nHere, we publish the scRNA, scDNA, and bkRNA data of the melanoma cohort.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-21T11:20:15.991812+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000600","title":"High-resolution profile of neoantigen-specific TCR activation links moderate stimulation to increased resilience of engineered TCR-T cells","description":"Neoantigen-specific T cell receptors (neoTCRs) promise safe, personalized anti-tumor immunotherapy. Previously, we identified diverse neoTCRs restricted to different neoantigens in a melanoma patient. In this work, we now combined single-cell TCR- and RNA-sequencing after neoantigen-specific restimulation of peripheral blood-derived CD8+ T cells of this patient. We detected novel neoTCRs with specificity to the previously detected neoantigens and observe a heterogeneous spectrum of TCR-intrinsic activation patterns in response to a shared neoepitope ranging from previously detected higher frequent neoTCRs with moderate activation to rare ones with initially stronger activation.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-22T09:38:00.954687+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000601","title":"Multiple paralogues and recombination mechanisms contribute to the high incidence of 22q11.2 Deletion Syndrome ","description":"To enable haplotype-specific assembly and rearrangement mapping in LCR22 clusters, we combined fiber-FISH optical mapping with whole genome (ultra-)long read sequencing or rearrangement-specific long-range PCR on 254 duos families (22q11.2DS patient and parent-of-origin) comprising several different LCR22-mediated rearrangements.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-10T15:18:58.766483+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000602","title":"Reconstructing oral cavity tumor evolution through brush biopsy","description":"Oral potentially malignant disorders (OPMDs) with genomic alterations have a heightened risk of evolving into oral squamous cell carcinoma (OSCC). Currently, genomic data are typically obtained through invasive tissue biopsy. However, brush biopsy is a non-invasive method that has been utilized for identifying dysplastic cells in OPMD but its effectiveness in reflecting the genomic landscape of OPMDs remains uncertain. This pilot study investigates the potential of brush biopsy samples in accurately reconstructing the genomic profile and tumor evolution in a patient with both OPMD and OSCC.  We analyzed single nucleotide variants (SNVs), copy number aberrations (CNAs), and subclonal architectures in paired tissue and brush biopsy samples. The results showed that brush biopsy effectively captured 90% of SNVs and had similar CNA profiles as those seen in its paired tissue biopsies in all lesions.  It was specific, as normal buccal mucosa did not share these genomic alterations. Interestingly, brush biopsy revealed shared SNVs and CNAs between the distinct OPMD and OSCC lesions from the same patient, indicating a common ancestral origin. Subclonal reconstruction confirmed this shared ancestry, followed by divergent evolution of the lesions. These findings highlight the potential of brush biopsies in accurately representing the genomic profile of OPL and OSCC, proving insight into reconstructing tumor evolution.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-03T16:24:16.360533+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000603","title":"scRNAseq + TCRseq of n-irAE patients","description":"Here we performed multimodal analysis (5'scRNAseq and TCR-seq) on PBMCs from cancer patients developing or not neurological adverse events (n-irAEs) following immune checkpoint inhibition (ICI) treatment.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000604","title":"Population-level analysis of temporal gene expression variation in peripheral blood","description":"Assessment of longitudinal inter- and intra-individual RNA expression variation in 333 healthy individuals from a population-based cohort at three different time points","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-25T12:27:58.382273+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000605","title":"Biopsy-Derived Organoids in Personalised Early Breast Cancer Care: Challenges of Tumour Purity and Normal Cell Overgrowth Cap Their Practical Utility","description":"The ability to establish organoids composed exclusively of tumour rather than healthy cells is essential for their implementation into clinical practice. Organoids have in recent years emerged as a powerful tool to expand patient material in culture and generate modifiable 3D models derived from humans or animal models.  For translational research, they enable the creation of model systems for an ever-increasing number of cell types and diseases. And in personalised medicine, they potentially allow for functional drug testing with high predictive power in certain settings. We found that using biopsy material from untreated, early-stage primary breast cancer patients poses significant challenges for consistently culturing tumour cells as organoids. Specifically, we observed frequent outgrowth of genetically normal, non-cancerous epithelial cells. We analysed >100 biopsy samples from early-stage breast cancer and present our large collection of >70 organoid lines. We also show methods of assessing successful tumour cell culture in a time and cost-efficient manner, proving a high rate (>85%) of normal cell overgrowth in early-stage breast cancer organoids. Finally, we show a number of successful attempts to culture cancer organoids from mastectomy-derived tissue of advanced, metastatic breast cancer. We conclude that the usefulness of organoids from early breast cancer for translational research and personalised medicine, especially guidance of adjuvant or post-surgical maintenance therapy, is strongly limited by the low success rate of culturing cancerous cells under organoid conditions.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-28T13:21:44.085986+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000606","title":"Rare germline variants in patients with personal and family history of colorectal cancer","description":"A double primary colorectal cancer (CRC) in a familial setting signals a high risk of CRC. In order to find novel high/moderate penetrance CRC susceptibility genes, we performed whole-exome sequencing on germline blood samples of seven familial cases from Poland with a double primary CRC.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-15T15:04:04.119683+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000607","title":"Chemotherapy induces myeloid-driven spatial T-cell exhaustion in ovarian cancer","description":"Gene expression profiles of single cells from 26 chemo-naïve and IDS tumor tissue and ascites samples from 17 HGSC patients","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-21T15:23:27.205044+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000608","title":"Chromatin landscapes and cell-free DNA fragmentation in colorectal cancer development","description":"The stepwise progression of colorectal cancer from healthy epithelium to premalignant adenoma and cancer is accompanied by genome-wide epigenetic reprogramming but current analyses of these processes have been hampered by complex mixtures of cells in tissue samples, as well as absence of suitable adenoma model systems.  Cultured colorectal organoids, comprised of pure epithelial cells, could enable sensitive analyses of epigenetic changes during progression from healthy tissue to cancer.  We aim to assay patient-derived colorectal organoids cultured from healthy, adenoma, and cancer tissues in order to identify genomic loci which exhibit changes in chromatin accessibility during this progression.  We also assay chromatin accessibility in peripheral blood mononuclear cells (PBMCs) as an external point of comparison.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000609","title":"WGS of pre-T cell receptor-alpha immunodeficiency proband and family ","description":"In this study, we describe the role of whole genome sequencing (WGS) in providing a definitive diagnosis for a child with T cell deficiency, where targeted panel sequencing of SCID genes and whole exome sequencing had failed. A novel homozygous 8kb deletion in PTCRA, encoding pTCR, was identified. WGS sequence data from the proband, proband’s mother, and proband’s father are deposited.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-24T15:53:20.884155+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000610","title":"CLL single cell profiling","description":"Genes involved in RNA splicing such as SF3B1 and U1 are frequently mutated in CLL, leading to altered splicing and generation of tumor neoepitopes. To study how these mutations impact the tumor microenvironment (TME), we conducted an in-depth profiling of CLL using single-cell sequencing in 26 bone marrow or lymph node tumor samples from 23 U-CLL patients with mutations in U1 (n=7), SF3B1 (n=8), or without mutations in splicing genes (n=10). ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000611","title":"EARLY DIAgnosis of PAncreatic Cancer (EARLY DIAPAC) study","description":"Whole genome sequencing of pancreatic cyst fluid for early detection and diagnosis of pancreatic cancer.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-28T11:10:52.099268+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000612","title":"Single cell transcriptome analysis of pediatric acute megakaryoblastic leukemia","description":"Pediatric acute megakaryoblastic leukemia presenting fusion oncogene is generally associated with a poor prognosis. We performed single transcriptome analyses on bone marrow samples from pediatric acute megakaryoblastic leukemia patients presenting the ETO2-GLIS2 fusion oncogene.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000613","title":"Genomic profiling of two pathogenic germline truncating variants of BRCA2 confer different haploinsufficiency phenotype","description":"Observation of the loss of heterozygosity of BRCA2 ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-29T13:32:05.587564+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000614","title":"Transcriptomic profiles of two pathogenic germline truncating variant of BRCA2","description":"Observation of the impact of two truncating variants of BRCA2 on the expression data","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-29T13:32:05.587564+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000615","title":"Genomic profiling of Rare Tumors Release 2","description":"Utilizing the rare and unique patient samples provided by Pattern Medicine, LLC, MD Anderson will molecularly characterize rare cancer samples, and potentially generate a collection of preclinical models to enable identification of novel therapeutic targets and concepts, as well as evaluation of innovative treatment strategies.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-14T15:10:06.421398+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000616","title":"Fibrosis associated loss of hepatic zonation in human NAFLD","description":"Understanding the molecular changes underlying liver fibrosis progression in non-alcoholic fatty liver disease (NAFLD) is critical for developing targeted therapies. We aimed to investigate the impact of fibrosis on transcriptional and epigenetic hepatic zonation in human liver tissue.\r\nWe utilized laser capture microdissection to isolate hepatocytes from pericentral, intermediate, and periportal zones of healthy and fibrotic liver tissues from NAFLD patients. RNA-seq and Reduced Representation Bisulfite Sequencing were performed to assess transcriptional and DNA methylation profiles, respectively.\r\nIn fibrotic liver tissue, we observed a loss of transcriptional zonation, with pericentral genes downregulated and periportal genes upregulated. This loss correlated with a reduction in DNA methylation zonation and remodeling of epigenetic landscapes, particularly in fibrosis-specific differentially methylated regions associated with pro-inflammatory pathways. Integration of gene expression and methylation data revealed disruption of DNA methylation gradients at transcription factor binding sites (TFBS), implicating dysregulated TF signaling in fibrogenesis.\r\nOur findings demonstrate the progressive loss of transcriptional hepatic zonation and remodeling of DNA methylation gradients in fibrotic liver tissue, suggesting a portalization phenotype of pericentral hepatocytes as a major hallmark of progressed liver fibrosis in NAFLD.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000617","title":"Single nuclei sequencing (snRNA-seq) of patient tumours","description":"snRNA-seq was performed on patient samples","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-28T11:35:30.175903+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000618","title":"Acetalax and bisacodyl triple-negative breast cancer RNA-Seq","description":"Analysis of gene expression in triple negative breast cancer xenografts exhibiting good or bad response upon acetalax and bisacodyl treament.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-14T15:12:06.56783+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000619","title":"Genomic characterization of germ-cell tumors in childhood","description":"Germ cell tumors (GCTs) are rare neoplasms affecting approximately 3.5% of pediatric patients, with diverse histological subtypes. Despite their low mutational burden, prevalent alterations in KIT, KRAS, and NRAS genes are observed, but molecular understanding of pediatric GCTs lags behind adult counterparts. We aimed to elucidate the genomic landscape of 16 pediatric GCT patients via whole exome sequencing (WES), which revealed somatic alterations resembling those in adult GCTs.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000620","title":"RNAseq of idelalisib treated CLL patients","description":"RNAseq of paired samples of CLL patients from before and during idelalisib therapy in vivo (n=18 samples from 9 patients).","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-14T11:17:29.674092+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000621","title":"RNAseq of ibrutinib treated CLL patients","description":"RNAseq of paired samples of CLL patients from before and during ibrutinib therapy in vivo (n=22 samples from 11 patients).","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-14T11:19:29.561119+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000622","title":"Oncogenic FOXL2C134W has gain-of-function chromatin remodeling activity that reprograms glucocorticoid receptor occupancy to promote ovarian granulosa cell tumor growth","description":"Adult type ovarian granulosa cell tumors (AGCTs) are rare malignancies with near universal somatic mutation c.C402G (p.Cys134Trp) in FOXL2, a forkhead box-family transcription factor important for ovarian function. Relapsed AGCT is incurable and the mechanism of the unique FOXL2 mutation remains incompletely understood. To identify FOXL2C134W-dependent pharmacologic synergies, we created and characterized endogenous FOXL2 isogenic AGCT cells and an AGCT tumoroid biobank. A drug screen identified that glucocorticoids promote FOXL2C134W-dependent AGCT growth. Epigenetic investigation revealed that the Cys134Trp mutation exposes latent DNA sequence-specific pioneering activity in FOXL2, a unique oncogenic mechanism. FOXL2C134W pioneering activity redirects glucocorticoid receptor chromatin occupancy to drive hyaluronan synthase 2 gene expression and increase extracellular hyaluronan secretion. Treatment of AGCT models with hyaluronidase reduces viability and this effect can be rescued by dexamethasone. Thus, gain-of-function pioneering activity contributes to the oncogenic mechanism of FOXL2C134W and creates a potentially targetable synergy with glucocorticoid signaling.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-31T12:38:40.58827+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000623","title":"Multi-omics analysis of CUD in the VS","description":"The aim was to molecularly characterize the human ventral striatum in CUD. For this, we generated epigenomic, transcriptomic, and proteomic datasets at the bulk-level, performed integrative multi-omics analyses and further analyzed CUD-associated transcriptomic changes at a cell type-specific level using snRNA-seq. ","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-22T17:18:39.670392+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000624","title":"IMPRESS: Improved methylation profiling using restriction enzymes and smMIP sequencing, combined with a new biomarker panel, creating a multi-cancer detection assay","description":"Background\r\nDespite the worldwide progress in cancer diagnostics, more sensitive diagnostic biomarkers are needed. The methylome has been extensively investigated in the last decades, but a low-cost, bisulfite-free detection method for multiplex analysis is still lacking.\r\nMethods\r\nWe developed a methylation detection technique called IMPRESS, which combines methylation-sensitive restriction enzymes and single-molecule Molecular Inversion Probes. We used this technique for the development of a multi-cancer detection assay for eight of the most lethal cancer types worldwide. We selected 1791 CpG sites that can distinguish tumor from normal tissue based on DNA methylation. These sites were analysed with IMPRESS in 35 blood, 111 tumor and 114 normal samples. Finally, a classifier model was built.\r\nResults\r\nWe present the successful development of IMPRESS and validated it with ddPCR. The final classifier model discriminating tumor from normal samples was built with 358 CpG target sites and reached a sensitivity of 0.95 and a specificity of 0.91. Moreover, we provide data that highlight IMPRESS’s potential for liquid biopsies.\r\nConclusions\r\nWe successfully created an innovative DNA methylation detection technique. By combining this method with a new multi-cancer biomarker panel, we developed a sensitive and specific multi-cancer assay, with potential use in liquid biopsies.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-16T12:40:04.629663+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000625","title":"Arcagen - Head and Neck domain","description":"Arcagen is an EORTC/SPECTA pan-European project that aims to recruit 1000 rare cancer patients from different tumour domains of EURACAN. This study collected samples from advanced or metastatic rare cancer from patients older than 12, and analysed them using Foundation Medicine next-generation sequencing (NGS) panels (FoundationOne CDx for FFPE samples or FoundationOne Liquid CDx for blood samples). Here were are submitting the dataset that contains NGS files from patients with salivary gland tumors of major salivary gland; salivary gland type tumors of head and neck with a strong focus on acinic cell carcinoma, NUT carcinoma and sinus carcinoma (n=102).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-02T14:12:14.972738+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000626","title":"Arcagen – Adrenal and Thyroid cancers domain","description":"Arcagen is an EORTC/SPECTA pan-European project that aims to recruit 1000 rare cancer patients from different tumour domains of EURACAN. This study collected samples from advanced or metastatic rare cancer from patients older than 12, and analysed them using Foundation Medicine next-generation sequencing (NGS) panels (FoundationOne CDx for FFPE samples or FoundationOne Liquid CDx for blood samples). Here were are submitting the dataset that contains NGS files from patients with adrenocortical carcinoma, pheochromocytoma, anaplastic thyroid cancer, medullary thyroid cancer and radioiodine refractory thyroid cancer (n=103).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-02T14:12:16.865136+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000627","title":"A comprehensive DNA methylation landscape of human and mouse cell lines derived from hematological malignancies","description":"Human cancer cell lines constitute useful models to study the primary disease and many relevant findings in tumor biology have been originated from them since the first immortalized cell line (HeLa) was obtained. The easy experimental intervention, the purity of the transformed cells and their versatility to undergo high-throughput screenings represent advantageous features of the established cancer cell lines. In recent years, major efforts have characterized in detail the multiomics make-up of hundreds of cancer cell lines and studied their association with sensitivity to anticancer drugs. Most of these studies have been genetic-centric and have not characterized in detail the epigenetic profiles underlying the characteristics of these cells or their impact on the efficacy of antitumoral compounds. In this regard, a past version of a DNA methylation microarray  or a less accessible and more time-consuming such as reduced representation bisulfite sequencing have been used in those attempts to interrogate the epigenetic setting. Herein, we have obtained the DNA methylation profiles of 210 cell lines derived from hematological malignancies utilizing comprehensive DNA methylation microarrays that interrogates more than 850,000 and 285,000 CpG sites from human and mouse genomes, respectively. Importantly, we also provide a pharmacoepigenetic example of the potential use of this resource by showing how DNA methylation can predict response to nucleoside analogues.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-21T15:54:09.394297+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000628","title":"10x genomics single cell RNA-seq and ATAC-seq from 10 pre-menopausal patients fimbriae and ampullary part of the fallopian tube","description":"The fallopian tube, connecting the uterus with the ovary, is a dynamic organ that undergoes cyclical changes and is the site of several diseases, including serous cancer. Here, we use single-cell technologies to construct a comprehensive cell map of healthy pre-menopausal fallopian tubes, capturing the impact of the menstrual cycle and menopause on different fallopian tube cells at the molecular level. The comparative analysis between pre- and post-menopausal fallopian tubes reveals substantial shifts in cellular abundance and gene expression patterns, highlighting the physiological changes associated with menopause. Further investigations into menstrual cycle phases illuminate distinct molecular states in secretory epithelial cells caused by hormonal fluctuations. The markers we identified characterizing secretory epithelial cells provide a valuable tool for classifying ovarian cancer subtypes.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-22T08:23:10.172444+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000629","title":"SU2C GSC DNAm","description":"SU2C GSC DNAm data new to Whitley et al. 2024 publication, adds to data produced in Guilhamon 2021 eLife publication","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000630","title":"Sensitive urothelial cancer detection via high volume urine DNA analysis","description":"Cystoscopy and imaging are the gold standard for urothelial cancer (UC) detection and surveillance, but cystoscopy is an uncomfortable procedure associated with adverse effects and a low diagnostic yield as only 10% of hematuria patients have UC. Urine tumor DNA (utDNA) is a non-invasive UC biomarker that has suffered from poor sensitivity for Ta stage tumors (<80%). We hypothesized that high urine volume analysis with a multi-gene panel could overcome these limitations, and developed a 100 mL utDNA laboratory platform (UroScout) that analyzes 25 commonly mutated UC genes and 8 copy number-altered loci for somatic alterations to detect UC.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-21T14:31:16.081288+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000631","title":"Diversity of the immune microenvironment and response to checkpoint inhibitor immunotherapy in mucosal melanoma","description":"Mucosal melanoma (MucM) is a rare cancer with a poor prognosis and low response rate to immune checkpoint inhibition (ICI) compared to cutaneous melanoma (CM). To explore the immune microenvironment and potential drivers of MucM’s relative resistance to ICI drugs, we characterized 101 MucM tumors (43 head and neck, 31 female urogenital, 13 male urogenital, 11 anorectal, and 3 other gastro-intestinal) using bulk RNA-sequencing (RNAseq). The original publication is written by JL Vos, JJH Traets, et al. and published in JCI Insight in 2024.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-28T09:40:59.049727+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000632","title":"Adaptive long-read and transcriptome sequencing detail a submicroscopic inv(15)(q14q15), generating two fusion transcripts and MEIS2 and NUSAP1 haploinsufficiency","description":"Study an inversion affecting MEIS2 using ONT adaptive sequencing.","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-22T16:25:47.749773+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000633","title":"human CMV-specific CD8+ T cells","description":"In this study we established a comprehensive workflow to collect multi-omics single-cell data\r\nusing a commercially available micro-well based platform. This included whole transcriptome,\r\ncell surface markers (targeted sequencing-based cell surface proteomics), T cell specificities,\r\nadaptive immune receptor repertoire (AIRR) profiles and sample multiplexing. With this\r\ntechnique we identified novel paired T cell receptor sequences for three prominent human\r\nCMV epitopes. In addition, we review the ability of dCODE dextramers to detect antigenspecific\r\nT cells at low frequencies by estimating sensitivities and specificities when used as\r\nreagents for single-cell multi-omics.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-27T10:45:24.959411+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000634","title":"SU2C GSC ATAC-seq","description":"ATAC-seq data produced by Lupien Lab (PMCC, University of Toronto) from GSC lines from Dirks Lab (SickKids, University of Toronto) for Whitley et al. 2024 manuscript (second half of Owen Whitley's thesis, University of Toronto)","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000635","title":"DAC-2020-03-26-Lemola (DAC-039))","description":"This is only the location.\r\nFor the raw data and any check if the dataset may be relevant please refer to the Harvard Dataverse (https://dataverse.harvard.edu/dataverse/lemola).","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[30772694],"external_links":[{"url": "https://dataverse.harvard.edu/dataverse/lemola", "name": "EucanImage", "label": "Harvard Dataverse"}, {"url": "https://usbch.sharepoint.com/:w:/r/sites/dkf/datarequests/MF-DAC/MF-DAC-requests/DAC-2020-03-26-Lemola/DAC-039%20DAC%20EGA%20Setup/00%20MF-DAC_Data%20Request%20Summary%20for%20DAC-2020-03-26-Lemola.docx?d=w159769d0806d489fa058ad7f5bb818f3&csf=1&web=1&e=Atp6cW", "name": "PRIDE", "label": "Summary Document"}],"is_released":true,"released_date":"2024-10-21T14:34:34.38123+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000636","title":"Spatial Profiling of Patient-Matched HER2 Positive Gastric Cancer Reveals Resistance Mechanisms to Trastuzumab and Trastuzumab Deruxtecan Sequencing","description":"HER2-positive gastric cancer (HER2+ GC) exhibits significant intra-tumoral heterogeneity and frequent development of resistance to HER2-targeted therapies. This study aimed to characterize the spatial tumor microenvironment (TME) and identify mechanisms of resistance to HER2 blockade including trastuzumab and trastuzumab deruxtecan (T-DXd) in HER2+ GC, with the goal of informing novel therapeutic strategies. We performed spatial transcriptomics on pre- and post-treatment samples from patients with HER2+ metastatic GC who received trastuzumab-based therapy. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-24T11:53:17.163948+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000637","title":"SU2C GSC miRNA-seq","description":"miRNA-seq for SU2C cohorts","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000638","title":"Altered Blood and Keratinocyte microRNA/transfer RNA Fragment Profiles Related to Fibromyalgia Syndrome and its Severity","description":"We provide small RNA transcriptome signatures of whole blood and cultured keratinocytes, which separate FMS patients from healthy controls. This opens new perspectives for FMS diagnostics, symptom monitoring, and clinical management.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-27T11:43:39.173533+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000639","title":"Arcagen - Sarcoma domain","description":"Arcagen is an EORTC/SPECTA pan-European project that aims to recruit 1000 rare cancer patients from different tumour domains of EURACAN. This study collected samples from advanced or metastatic rare cancer from patients older than 12, and analysed them using Foundation Medicine next-generation sequencing (NGS) panels (FoundationOne CDx for FFPE samples or FoundationOne Liquid CDx for blood samples). Here we are submitting the dataset that contain NGS files from patients with undifferentiated sarcoma of the bone; aggressive angiomyxoma; alveolar soft part sarcoma; small round cell sarcoma without EWSR1 and CIC translocations; undifferentiated pleomorphic sarcoma; undifferentiated sarcoma; myxofibrosarcoma; or sarcoma with an incidence of less than 1 per 10 million (n=62).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-02T14:12:18.870192+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000640","title":"Singapore Gastric Cancer Consortium GeoMx DSP tissue microarray (SGCC TMA) cohort","description":"Gastric cancer (GC) remains a significant global health challenge due to its high heterogeneity, with intratumoral heterogeneity (ITH) posing a major obstacle to effective patient outcomes. In this study, utilizing GeoMx Digital Spatial Profiler (DSP) technology, we specifically investigated ITH within GC patients by comparing tumor core regions to tumor edge regions. Our findings indicate that tumor edge regions exhibit more advanced tumor activity, akin to the G2-like progressed state, compared to tumor core regions. The findings confirm the spatial locations of G2\r\nRNA-ITH subregions and support the conclusions drawn from the discovery cohort.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-23T15:32:26.41451+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000641","title":"IDH- and H3-wildtype high-grade gliomas in teenagers and young adults","description":"Whole exome sequencing of high grade gliomas occurring in teenagers and young adults between the ages of 13 and 30. This study combines methylation array profiling, whole exome sequencing and fusion panels sequencing to provide and integrated diagnosis of tumours in this age group.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-15T18:17:45.935601+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000642","title":"Comprehensive molecular portrait reveals genetic diversity and distinct molecular subtypes of small intestinal neuroendocrine tumors","description":"This study aims to characterize neuroendocrine tumors of the small intestine (siNETs) from genomic, transcriptomic, epigenomic, and clinical perspectives. Involving 122 patients and 219 samples, we generated whole-genome sequencing data, RNA sequencing data, genotyping arrays, and methylation arrays to conduct an integrative analysis of this rare tumor type. Our findings identify distinct molecular subtypes that correlate with siNET clinical features.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-20T15:02:09.309851+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000643","title":"ctDNA multigenic panel for non-small cell lung cancer","description":"Detection of actionable mutations in liquid biopsies constitute an important tool for\r\nmanagement of non-small cell lung cancer (NSCLC) patients in the era of oncology precision\r\nmedicine. We aimed to evaluate the actionable alterations using a commercial multi-gene panel in\r\ncirculating tumor DNA (ctDNA) derived from plasma samples of treatment naïve and prior-treated\r\nnon-small cell lung cancer (NSCLC) patients. For this, we analyze plasma samples of 30 subjects with\r\nnon-small cell lung cancer.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-20T15:11:24.954172+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000644","title":"Arcagen - Extra-pulmonary neuroendocrine tumour or cancer grade 3 (NET / NEC G3) domain","description":"Arcagen is an EORTC/SPECTA pan-European project that aims to recruit 1000 rare cancer patients from different tumour domains of EURACAN. This study collected samples from advanced or metastatic rare cancer from patients older than 12, and analysed them using Foundation Medicine next-generation sequencing (NGS) panels (FoundationOne CDx for FFPE samples or FoundationOne Liquid CDx for blood samples). Here were are submitting the dataset that contains NGS files from patients with extra-pulmonary neuroendocrine tumour or cancer grade 3 (NET / NEC G3) (n=85).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-20T10:19:50.876557+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000645","title":"Arcagen - Relapsing germ cell tumors domain","description":"Arcagen is an EORTC/SPECTA pan-European project that aims to recruit 1000 rare cancer patients from different tumour domains of EURACAN. This study collected samples from advanced or metastatic rare cancer from patients older than 12, and analysed them using Foundation Medicine next-generation sequencing (NGS) panels (FoundationOne CDx for FFPE samples or FoundationOne Liquid CDx for blood samples). Here we are submitting the dataset that contain NGS files from patients with Relapsing germ cell tumors, of any origin and of any histological type (n=23).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-02T14:12:20.858899+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000646","title":"Host factors dictate gut microbiome alterations in chronic kidney disease more strongly than to kidney function","description":"Despite recent progress, microbial markers in Chronic Kidney Disease (CKD) remain inconclusive. We combined quantitative faecal metagenomics (N=130 CKD cohort) and cross-study biomarker comparisons (Ntotal=4420) to study microbiome associations with glomerular filtration rate (eGFR; kidney function) and 4-year CKD progression. Transit time (TT) and medications primarily explained microbiome variation, trumping eGFR-related effects. Metagenome analysis showed increased p-cresol and indole synthesis potential and decreased plant-to-animal CAZyme ratios with lower eGFR, coupled to a Bact1 to Rum enterotype shift, suggesting saccharolytic-to-proteolytic microbiome transitions linked to dietary guidelines and slowed-down TT. Peritoneal dialysis patients showed increased (dysbiotic) Bact2 prevalence and linked intestinal inflammation. Only Escherichia coli, an unnamed Alistipes species and Bifidobacterium adolescentis were confounder-independent markers for eGFR, but these nor previous markers convincingly replicated across 11 studies. No predictors for CKD progression were found. Together, poor evidence for microbiome biomarkers but substantial eGFR-independent effects were found, suggesting potential for nutritional and TT interventions in CKD.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000647","title":"Transcriptomic profiling of fragile X syndrome unmethylated full mutation carriers ","description":"Total RNA sequencing of fibroblasts from two unrelated FMR1 unmethylated full mutation carriers, a fragile X patient and a control individual. The existence of rare, unmethylated full mutation carriers who carry the mutation that causes fragile X syndrome but do not gain methylation at the locus offers a rare opportunity to study the mechanisms underlying fragile X syndrome. This study aims to compare the transcriptomes of these four individuals in order to elucidate the mechanism behind the methylation a the FMR1 CGG repeat expansion that causes Fragile X syndrome.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-16T17:08:42.205072+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000648","title":"Genomic profiling of fragile X syndrome unmethylated full mutation carriers ","description":"Whole genome sequencing of two unrelated FMR1 unmethylated full mutation carriers. The existence of rare, unmethylated full mutation carriers who carry the mutation that causes fragile X syndrome but do not gain methylation at the locus offers a rare opportunity to study the mechanisms underlying fragile X syndrome. This study aims to investigate the genomic variants in these individuals alongside transcriptomic data to elucidate underlying genomic variants behind transcriptomic differences observed in UFM individuals.\r\n","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-16T17:08:38.041055+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000649","title":"MDS 5q exomes","description":"This project aimed to study the somatic alterations present in myelodysplastic syndromes patient with isolated chromosome 5q deletion. It was emphasized in analysing TP53 alterations, including mutations and copy number alterations affecting chromosome 17. \r\nExome data from five patients that were included in this project are shared in this submission. \r\n","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-10-22T17:21:24.373051+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000650","title":"WES data from primary CRCs tissues in ctDNA positive patients","description":"Whole exome data from primary colorectal cancer tissue samples were analysed in patients where mutations where found in circulating tumour DNA.  DNA was extracted from FFPE blocks and exome libraries were prepared using the KAPA HyperPlus Kit (Roche diagnostics)","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-15T14:22:43.148127+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000651","title":"Nanopore whole-genome sequencing of human sarcomas","description":"We performed single and multi-region nanopore whole-genome sequencing on human sarcoma samples from adult and paediatric patients.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[39814020],"external_links":null,"is_released":true,"released_date":"2024-12-18T14:00:22.118938+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000652","title":"analysis of immune infiltration in colorectal cancer metastasis","description":"Metastatic colorectal cancer (mCRC) is the main cause of CRC mortality, with limited treatment options. Although immunotherapy has benefited some cancer patients, mCRC typically lacks the molecular features that respond to this treatment. However, recent studies indicate that the immune microenvironment of mCRC may be modified to enhance the effect of immune checkpoint inhibitors. This study aimed to explore the metastatic immune microenvironment by comparing immune cell populations in colorectal liver (CLM), lung (mLu) and peritoneal (PM) metastases. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-08T10:56:19.092385+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000653","title":"Single-cell spatiotranscriptomic dissection of ex vivo human heart right atrial appendage and pericardial fluid in ischemic heart disease and heart failure","description":"We use cardiac and pericardial fluid biopsies collected during open-heart surgery in control, ischemic heart disease, heart failure, and myocardial infarction context. For each sample, single-nuclei RNA sequencing experiment is performed. We also perform spatial transcriptomics on the heart samples. We annotate the cells in major cell types, in addition to subtypes annotation of vascular and immune cells. The disease annotation enables us to reveal substantial differences in gene expression at the cell subpopulation levels. Our results demonstrate the importance of high-resolution cellular type/state mapping in the elucidation of human cardiovascular disease pathogenesis.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[38776872],"external_links":null,"is_released":true,"released_date":"2024-12-16T17:01:56.077635+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000654","title":"PBMC","description":"Whole-Exome-Sequencing of 5 pooled patients for SNP-based demultiplexing","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-07T11:50:38.346522+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000655","title":"Heart","description":"Whole-Exome-Sequencing of 5 pooled patients for SNP-based demultiplexing","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-07T11:50:38.346522+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000656","title":"Changes in CRISPR/Cas9 Outcomes depending on the usage of Pifithrin-alpha","description":"Study of the effects of Pifithrin-alpha in the context of genetic-engineering in primary human T cells.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-06T16:32:44.132423+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000657","title":"Genetic architecture of disease in Greenland is shaped by demographic history, fine-structure, and selection - WGS data","description":"This data was generated as part of the project titled \"Genetic architecture of disease in Greenland is shaped by demographic history, fine-structure, and selection.\" The study was carried out to investigate the genetic architecture of the Greenlandic population and the consequences it has for disease mapping, diagnosis and prediction.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-07T11:56:41.342755+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000658","title":"Genetic architecture of disease in Greenland is shaped by demographic history, fine-structure, and selection - MEGA chip data","description":"This data was generated as part of the project titled \"Genetic architecture of disease in Greenland is shaped by demographic history, fine-structure, and selection.\" The study was carried out to investigate the genetic architecture of the Greenlandic population and the consequences it has for disease mapping, diagnosis and prediction.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-07T11:56:42.563016+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000659","title":"Organoid BulkRNAseq","description":"Here, we aim to understand early determinants of brain organoid quality and generated a set of brain organoids from 12 different hPSC lines using an adaptation of the unguided Lancaster protocol (Lancaster & Knoblich, 2014). All cell lines were obtained from healthy donors. 12 donor hPSC lines were differentiated into brain organoids and a set of 72 individual organoids (6 per line) were randomly selected morphologically diverse organoids and subjected to bulk RNA sequencing for gene expression analysis. \r\n\r\nRNA was extracted using the RNeasy kit (Qiagen, Germany) according to the manufacturer’s instructions. A total of 1000 ng per sample was sent for RNA sequencing to Azenta Life Sciences (Genewiz Leipzig, Germany) for sequencing. Library preparation was performed using the NEBNext Ultra II RNA Library Prep Kit for Illumina following manufacturer’s instructions (NEB, Ipswich, MA, USA). mRNAs were first enriched with Oligo(dT) beads. The samples were sequenced using a 2x150 Pair-End (PE) configuration v1.5 at a depth of >20 million reads in each sample. Raw sequence data (.bcl files) generated from Illumina NovaSeq6000 was converted into fastq files and de-multiplexed using Illumina bcl2fastq program version 2.20. The raw sequence reads were aligned to the human reference genome GRCh38 using the STAR aligner (Dobin et al., 2013). Gene expression levels were quantified using the FeatureCounts tool (Liao et al., 2014).","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-07T11:53:01.770129+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000660","title":"Spatial atlas of human atherosclerosis highlights role of the microvasculature in disease ","description":"Atherosclerosis is a pervasive contributor to ischemic heart disease and stroke. Despite the advance of lipid lowering-therapies and antihypertensive agents, the residual risk of an atherosclerotic event remains high and developing therapeutic strategies has proven challenging. This is due to the complexity of atherosclerosis with a spatial interplay of multiple cell types within the vascular wall. Here we generate an integrative high-resolution map of human atherosclerotic plaques combining single-cell RNA-seq from multiple studies and spatial transcriptomics data from 12 human specimens, with different stages of atherosclerosis. We show cell-type and atherosclerosis-specific expression changes and spatially constrained alterations in cell-cell communication. We highlight the possible recruitment of lymphocytes via ACKR1 endothelial cells of the vasa vasorum, the migration of vascular smooth muscle cells towards the lumen by transforming into fibromyocytes, and cell-cell communication in the plaque region, indicating an intricate cellular interplay within the adventitia and the subendothelial space in human atherosclerosis.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-07T12:01:46.580451+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000661","title":"Determinants of DNA methylation patterning in human placental development and trophoblast stem cell models.","description":"To assess whether the DNA methylation landscape of human trophoblast stem cells resembles an in vivo cell type, we used post-bisulfite adaptor-tag sequencing to measure genome-wide DNA methylation of preimplantation human trophectoderm and sorted first trimester cytotrophoblast.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-23T10:18:21.100702+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000662","title":"Reconstitution of Human Brain Cell Diversity in Organoids via Four Protocols [scRNAseq]","description":"Single-cell RNA-sequencing of brain organoids at day 120 grown in four distinct growth protocols designed to generate dorsal (D) and ventral (V) forebrain, midbrain (M) and striatum (S) tissue using eight different pluripotent stem cell lines. Per per cell line-protocol combination two organoids (biological replicates) were grown. For cell line 176 the experiment was conducted in two independent biological replicates (repititions E1 and E2).","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-27T09:57:00.180703+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000663","title":"Reconstitution of Human Brain Cell Diversity in Organoids via Four Protocols [time-course bulkRNAseq]","description":"Time-course bulk-RNA sequencing of brain organoids grown in four distinct growth protocols designed to generate dorsal (D) and ventral (V) forebrain, midbrain (M) and striatum (S) tissue at days 13 (for dorsal and ventral)/16 (for midbrain and striatum), 25, 40, 80 and 120. Per per cell line-protocol-timepoint combination three organoids (biological replicates) were grown. For reference, also three samples of the pluripotent stem cells across cell lines, not yet exposed to any protocol, were sequenced (day 0, pluripotent). ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-27T09:57:00.180703+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000664","title":"Acquired resistance to BRAF inhibitory treatments requires tumor tissue remodeling and reveals targetable vulnerabilities in colorectal cancer","description":"The combination of BRAFV600E and EGFR inhibitors benefits advanced colorectal cancer (CRC) patients, but resistance can develop through non-genetic mechanisms not fully understood. This study reveals that BRAF mutant CRC tumors undergo a tissue remodeling to resist BRAFV600E inhibitors, characterized by tumor cell mucinous differentiation and extracellular matrix transformation, allowing an increased infiltration of activated fibroblasts, immune cells, and vasculature. Single-cell RNA sequencing was conducted on naive PDX models at the treatment endpoint to study intrinsic changes in the tumor cell population driven by BRAF inhibition in colorectal cancer.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000665","title":"Acquired resistance to BRAF inhibitory treatments requires tumor tissue remodeling and reveals targetable vulnerabilities in colorectal cancer","description":"The combination of BRAFV600E and EGFR inhibitors benefits advanced colorectal cancer (CRC) patients, but resistance can develop through non-genetic mechanisms not fully understood. This study reveals that BRAF mutant CRC tumors undergo a tissue remodeling to resist BRAFV600E inhibitors, characterized by tumor cell mucinous differentiation and extracellular matrix transformation, allowing an increased infiltration of activated fibroblasts, immune cells, and vasculature.Whole exome sequencing revealed an absence of oncogenic mutations that could account for the observed resistance, suggesting that non-genetic mechanisms, rather than the expansion of a specific genetic clone, may drive resistance to BRAFi therapies in mCRC.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000666","title":"Expression quantitative trait loci influence DNA damage-induced apoptosis in cancer","description":"The analysis of e2QTL allows for the identification of context-specific eQTL effects (Kim-Hellmuth et al. (2017), PMID: 28814792). To evaluate how inter-individual genetic variability influences the regulation of DNA damage-induced apoptosis, we performed e2QTL analysis of CD8+ T cells from 461 healthy European participants stimulated with high doses of 5 different carcinogens. These include Methyl-methanesulfonate (MMS), tert-butyl-hydroperoxide (TBOOH), benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE), 4-hydroxycyclophosphamide (HC) and UVC radiation.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-15T15:08:09.396052+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000667","title":"RNA-seq of longitudinal human blood and nose swab samples from a controlled human infection experiment with SARS-CoV-2 virus","description":"Controlled human infection experiments enable longitudinal profiling of immune responses to a pathogen. 36 healthy volunteers aged 18-29 years, with no evidence of previous infection or vaccination, were inoculated with SARS-CoV-2 virus and quarantined for 14 days. Blood samples for RNA sequencing were collected into PAXgene tubes before virus challenge, 6 hours after challenge, daily thereafter for 14 days and on day 28. Mid-turbinate nose swabs for RNA sequencing were collected before virus challenge, and on days 1, 3, 5, 7, 10 and 14 after challenge, preserved in RNAprotect.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-19T10:48:08.482443+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000668","title":"Multi-omics analysis reveals immune programs delineating disease severity in extrapulmonary tuberculosis","description":"This study investigates the immune response in extrapulmonary tuberculosis (EPTB) using a combination of bulk and single-cell RNA sequencing. Hierarchical clustering of patient transcriptomes identified three distinct levels of disease severity, uncovering immunological pathways involved in disease progression, including interferon and IL-1β-mediated signaling. The findings also led to the development of a diagnostic gene expression signature for both EPTB and pulmonary TB, offering potential improvements in TB diagnosis and treatment.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-02T18:59:16.022725+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000669","title":"Sarcopenia related to Head and Neck squamous cell carcinomas: transcriptome modifications of muscle cells induced by distant malignant cells","description":"The biological mechanisms of sarcopenia are still very poorly understood, particularly in the case of Head and Neck Squamous Cell Carcinomas (HNSCC). However, there is good reason to believe that diffusible factors originating from tumor cells exert a distant deleterious effect on muscle cells. To test this hypothesis we implemented a dual approach based both on experiments carried out in vitro and on the study of muscle fragments from patients.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-27T15:52:00.985367+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000670","title":"RNA-seq of PanNETs data","description":"This study contains raw RNA sequencing data from 174 pancreatic neuroendocrine tumor (PanNET) samples, collected to explore gene expression and alternative splicing patterns and their association with clinical and molecular characteristics. The data support further research into the role of alternative splicing in PanNET biology and its potential as a tool for biomarker and therapeutic target discovery.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000671","title":"Investigation of respiratory chain integrity in skeletal muscle in Parkinson's disease","description":"The aim of this study is to investigate mitochondrial dysfunction in skeletal muscle as a potential biomarker for identifying a distinct subtype of Parkinson’s disease (PD) characterized by mitochondrial complex I (CI) deficiency (CI-PD). Based on previous post-mortem findings, the study hypothesizes that widespread CI deficiency is present in a subset of PD patients and could be detectable in clinically accessible muscle samples. By analyzing mitochondrial function in muscle biopsies from individuals with PD and healthy controls, the study seeks to explore the extent of mitochondrial dysfunction in PD and identify a stratification marker for future diagnostic and therapeutic interventions.\r\nThis study is part of the STRAT-PARK initiative, a longitudinal cohort study that aims to stratify neurodegenerative parkinsonisms into biological subtypes using a biomarker-based approach (https://doi.org/10.1016/j.pneurobio.2024.102603).","abstract":null,"study_type":"Pooled Clone Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-01T13:03:12.762448+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000672","title":"A first-in-human clinical study of an allogenic iPSC-derived corneal endothelial cell substitute transplantation for bullous keratopathy","description":"iPSC-derived corneal endothelial cell substitutes recover pathological corneal edema. No adverse reactions are observed after one year follow-up. Gene mutations may appear despite whole genome sequencing of the master cell bank. This study contains WGS data.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-19T12:24:35.345579+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000673","title":"A first-in-human clinical study of an allogenic iPSC-derived corneal endothelial cell substitute transplantation for bullous keratopathy","description":"iPSC-derived corneal endothelial cell substitutes recover pathological corneal edema. No adverse reactions are observed after one year follow-up. Gene mutations may appear despite whole genome sequencing of the master cell bank. This study contains the RNA-seq data.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-19T12:24:36.767568+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000674","title":"Circulating tumour DNA (ctDNA) data of High Grade Serous Ovarian Cancer Patients","description":"This study contains circulating tumour DNA (ctDNA) data derived from longitudinal plasma samples of High Grade Serous Ovarian Cancer (HGSC) patients belonging to the DECIDER study (NCT04846933). Ovarian cancer kills more than 40 000 women in Europe each year, and HGSC is the most common and most difficult to treat subtype of this disease. This study contains different sequencing datasets with samples from different stages during the treatment of the patients.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-02T10:57:47.179491+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000675","title":"Spatial distribution of genomic heterogeneity in gallbladder adenocarcinoma","description":"Intratumoral heterogeneity and Darwinian selection are the core mechanism of cancer progression. Here, we illustrate the comprehensive landscapes of genomic heterogeneity and evolution of cancer subclones at the microscopic level using whole-genome sequences from 29 micropatches obtained from gallbladder adenocarcinoma.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000676","title":"Cellular metabolism senses exogenous fatty acids to reprogram dormant cancer cells into aggressive tumourigenic cell states","description":"During uncontrolled growth, cancer cells exhibit a spectrum of cellular states from highly oncogenic/stem cell-like to more quiescent/differentiated states. Here, using patient-derived liver cancer organoids we demonstrate that clonally identical tumour cells exhibit distinct tumourigenic potentials. Exposure to dietary long-chain fatty acids induce the reprogramming of quiescent/differentiated cells into highly aggressive tumour-promoting cells, both in vitro and in vivo.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000677","title":"Dynamics of tumor ecosystems and microbiome in response to neoadjuvant atezolizumab, bevacizumab, and FOLFOX treatment in patients with unresectable colorectal cancer with liver metastasis","description":"This study aims to explore the effects of neoadjuvant atezolizumab, bevacizumab, leucovorin, 5-fluorouracil, and oxaliplatin (ABFOLFOX) in patients with unresectable colorectal liver metastases (CRLM), focusing on the molecular dynamics of tumor ecosystems (TE) of CRLM and their impact on treatment outcomes.\r\n\r\nThe study comprises two cohorts with CRLM tissue samples analyzed with RNA sequencing and immunohistochemical staining: cross-sectional cohort A (n = 60, CRLM treated with or without neoadjuvant chemotherapy) and prospective cohort B (n = 20 with serial sampling and treated with ABFOLFOX). Shotgun metagenomic sequencing was done for stool samples from cohort B. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-29T16:56:02.501872+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000678","title":"Synthetic - GDI synthetic data","description":"Synthetic - The Genomic Data Infrastructure (GDI) project is enabling access to genomic and related phenotypic and clinical data across Europe. It is doing this by establishing a federated, sustainable and secure infrastructure to access the data. In support of FAIRness in data sharing, this dataset  is made freely available under the Creative Commons Licence (CC-BY). Please ensure the GDI project (funding: EC H2020 under grant agreement number 101081813) is acknowledged.","abstract":null,"study_type":"Synthetic Genomics","pubmed_ids":[26432245],"external_links":null,"is_released":true,"released_date":"2024-11-05T17:22:29.299091+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000679","title":"Transcriptome analysis of human longitudinal whole blood samples from PCR-positive and PCR-negative adults following controlled inoculation with Influenza A (H3N2) virus.","description":"Transcriptome analysis of influenza A (H3N2) human challenge samples. Understanding of the transcriptomic profile of individuals in early influenza infection is limited. To investigate this, longitudinal whole-blood samples (n=178) were taken from adult participants following controlled inoculation with Influenza A H3N2 virus (sampling at baseline (0) and days 1, 2, 3, 7, 10 and 14 post-challenge). Most participants became influenza PCR-positive; a minority remained PCR-negative. Total RNA was extracted from PAXgene tubes before undergoing globin and rRNA depletion. DNA libraries were constructed using the NEBNext® Ultra™ II Directional RNA Library Prep Kit for Illumina. All samples were then sequenced using Illumina NovaSeq 6000.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-19T10:48:09.752323+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000680","title":"RNA sequencing data from glioblastoma primary cell lines treated with indisulam","description":"This study aimed to develop NovumRNA, a bioinformatics pipeline designed to predict non-canonical tumor-specific antigens (ncTSAs) from human tumor RNA-sequencing data, potentially broadening the target pool for cancer neo-epitope-based immunotherapies. The splicing-modulating drug indisulam was investigated for its potential to induce aberrant transcriptomes, potentially increasing ncTSAs, subsequently predicted by NovumRNA. Four glioblastoma primary cell lines were derived from patient Cavitron Ultrasonic Aspirator (CUSA) material, cultured as neurospheres, and treated with indisulam or vehicle control. RNA was extracted at 6 and 16 hours post-treatment and sequenced using the NovaSeq platform. The resulting RNA-seq data was analyzed with NovumRNA, using healthy brain GTEx samples as controls, to identify and validate ncTSAs induced by indisulam treatment.\r\nNovumRNA is available at: https://github.com/ComputationalBiomedicineGroup/NovumRNA.\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-19T16:49:07.899579+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000681","title":"Study of biomarkers implicated in radio-immunotherapy response in metastatic cancer","description":"Immuno-radiotherapy may improve outcomes for patients with advanced solid tumors, although optimized combination modalities remain unclear. Here, we report the  analysis from the SABR-PDL1 (NCT02992912) trial that evaluated the PD-L1 inhibitor atezolizumab in combination with stereotactic body radiation therapy (SBRT) in patients with advanced cancer. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-02-12T15:54:33.474577+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000682","title":"Human dorsal root ganglia after plexus injury - RNA-fragment sequencing from histological slices","description":"Human dorsal root ganglia from patients with brachial plexus injury and from subjects from forensic autopsy were extracted and fixed with paraformaldehyde. The cellular composition of these DRG was analysed in histopathological slices. From some of the slices, total RNA was extracted and total RNAseq was performed. The RNA sequencing data represent DRG with neuronal preservation (n=6) or neuronal loss (n=2) versus control (n=6). \r\nDetails can be found in the corresponding publication and supplement to this publication.","abstract":null,"study_type":"RNASeq","pubmed_ids":[39393999],"external_links":null,"is_released":true,"released_date":"2024-11-20T08:27:56.133816+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000683","title":"RNA-Seq - Characterization of a Breast Patient-derived Tumor Organoid biobank from an underserved population of patients","description":"RNA-seq datasets of patient and patient-derived organoids","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-11T16:55:47.116678+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000684","title":"WES - Characterization of a Breast Patient-derived Tumor Organoid biobank from an underserved population of patients.","description":"EXaCT-2, an augmented WES assay, has been performed on a cohort of 4 patients and their corresponding organoids","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-11T16:55:48.341935+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000685","title":"RNA sequencing data from patient derived colorectal cancer organoids","description":"This study aimed to develop NovumRNA, a bioinformatics pipeline designed to predict non-canonical tumor-specific antigens (ncTSAs) from human tumor RNA-sequencing data, potentially broadening the target pool for cancer neo-epitope-based immunotherapies.\r\nThe pipeline was utilized to analyze RNA-seq data from ten patient-derived colorectal cancer (CRC) organoids, representing seven microsatellite stable (MSS) and three microsatellite instable (MSI) tumors. The goal was to explore the ncTSA landscape in CRC, particularly in MSS cases, which typically exhibit low tumor mutational burden and limited response to current immunotherapies. The study identified comparable ncTSA burdens across MSI and MSS tumors, suggesting new avenues for immunotherapy targeting non-canonical antigens in CRC.\r\nNovumRNA is available at: https://github.com/ComputationalBiomedicineGroup/NovumRNA.\r\n ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-19T10:09:49.658959+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000686","title":"The di-leucine motif in the host defense peptide LL-37 is essential for initiation of autophagy in human macrophages","description":"Different post-translational modifications (PTMs) like citrullination, acetylation, and formylation impact the human cathelicidin LL-37, yet their effect on autophagy remains unknown. Neutrophil-released LL-37 failed to induce autophagy, unlike macrophage-released LL-37. Mass spectrometry analysis revealed modifications on neutrophil-derived LL-37, especially at the N-terminal, while macrophage-derived LL-37 remained mostly native. Native LL-37 initiated autophagy, while formylated and acetylated versions did not. This data set contains RNAseq data from primary human macrophages and compares 4 conditions: Unstimulated macrophages, stimulation with native LL-37, stimulation with formylated LL-37, and stimulation with rapamycin.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000687","title":"Cell-type eQTLs for single-cell Mendelian Randomisation","description":"The following study mapped eQTLs in the post-mortem human brain from snRNA-seq generated on 391 individuals. Following eQTL discovery and identification of state-specific eQTLs (dynamic associations interacting with disease), colocalisation and MR was performed integrating GWAS from 42 traits, for the identification of putatively causal genes with cell-type specific context.\r\n\r\nThis study contains raw sequencing data and genotype for two datasets used in this work;\r\n\r\n- The MRC 60 dataset, which contains snRNA-seq generated on post-mortem brain from 60 control individuals (104 samples total, split across prefrontal cortex and hippocampus). Samples were pooled into 27 distinct pools, each of which was split across 4 lanes. Following sequencing and mapping using cellranger, demultiplexing was done using Demuxlet using the pool-specific genotype data (which contain sample IDs). \r\n\r\n- The Roche PD dataset, which is 10X multiome data generated on on 70 PD and 22 control individuals. \r\n\r\n","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-27T16:12:07.32841+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000688","title":"Targeting Heterochromatin Eliminates Malignant Stem Cells in Chronic Myelomonocytic Leukemia Through Reactivation of Retroelements and Innate Immune pathways","description":"Hematopoietic stem cell (HSC) aging involves heterochromatin reorganization. These repressive marks together with DNA methylation are essential for suppressing transposable elements (TEs). In this study we analyze heterochromatin and transcriptomic changes occurring at genes and TEs in HSCs from chronic myelomonocytic leukemia, a severe myeloid malignancy affecting the elderly, compared to age-matched cells, and in the presence or absence of a combination of epidrugs.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000689","title":"MOSAIC - Multi-Omics Spatial Atlas In Cancer","description":"MOSAIC is a collaborative initiative founded by Owkin, Lausanne University Hospital (CHUV), Charité Universitätsmedizin Berlin, University Hospital Erlangen (UKER), Gustave Roussy Institute in Paris, and University of Pittsburgh. The goal of MOSAIC is to build the largest collection of spatial omics data in cancer. By integrating comprehensive high quality clinical annotations with advanced deep profiling techniques, MOSAIC aims to uncover novel cancer subtypes and identify key drug targets and biomarkers within them.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-17T16:39:12.838294+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000690","title":"Transcriptomic profiles of tumor samples from patients with stage I-III TNBC treated with anthracycline-taxane chemotherapy plus fasting-mimicking diet plus/minus metformin in the context of the BREAKFAST trial (NCT04248998)","description":"BREAKFAST is a randomized, non-comparative, phase II trial enrolling stage I-III (cT>1cm) TNBC pts treated with neoadjuvant doxorubicin-cyclophosphamide q3w for 4 cycles, followed by weekly paclitaxel for 12 cycles. Pts were randomized 1:1 to receive: CT + triweekly 5-day FMD cycles (arm A), or CT + FMD + daily metformin (1700 mg) (arm B). The primary study objective was to investigate if one or both experimental treatments were able to increase pCR rates when compared to anthracycline-taxane CT alone according to historical data. Secondary/exploratory endpoints included biomarker analyses based on tumor transcriptomics analyses. Specifically, we collected fresh-frozen tumor samples at baseline and 14-21 days after the first treament cycle and we analyzed the RNA-seq profiles to identify early predictors of treatment activity. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-11T15:38:51.134308+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000691","title":"HIPSD&R-seq enables scalable genomic copy number and transcriptome profiling","description":"Single-cell DNA-sequencing (scDNA-seq) enables decoding somatic cancer variation. Existing methods are hampered by low throughput or cannot be combined with transcriptome sequencing in the same cell. We propose HIPSD&R-seq (HIgh-throughPut Single-cell Dna and Rna-seq), a scalable yet simple and accessible assay to profile low-coverage DNA and RNA in thousands of cells in parallel. Our approach builds on a modification of the 10X Genomics platform for scATAC and multiome profiling. In applications to human cell models and primary tissue, we demonstrate the feasibility to detect rare clones and we combine the assay with combinatorial indexing to profile over 17,000 cells.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-28T16:18:23.431299+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000692","title":"Fragmentomic features of individuals with different cfDNA concentrations","description":"The goal of this study is to explore fragmentomic patterns that vary between individuals of different concentrations of total cell-free DNA in plasma. We have selected a large cohort of individuals (ethnically Chinese men with a median age of 54 years, IQR 49-57) who were part of a screening of a large-scale clinical study to screen for nasopharyngeal carcinoma. Differences in fragmentomic features provided insights into the modulation of cfDNA levels in blood circulation. Fragmentomic and machine learning systems adopted in this study have also been applied to assess the quantity of cfDNA species of clinical interest, including the fraction of circulating fetal and tumor DNA, from pregnancy cases and individuals with hepatocellular carcinoma, respectively.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-02T16:18:32.122683+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000693","title":"Diversity of U1 small nuclear RNAs and Evaluation of Diagnostic Methods for their Mutations","description":"U1 small nuclear RNA (snRNA) mutations are recurrent non-coding alterations found in various malignancies, including medulloblastoma, yet their identification has proven challenging due to their repetitive nature. To establish a robust DNA-based, and RNA-based method for detecting U1 snRNA mutations, we performed targeted DNA sequencing using our original gene panel for medulloblastoma and RNA-sequencing. As an RNA-based method, we developed a random forest classifier employing splicing patterns which were massively altered as a result of U1 snRNA mutations. By using both methods, we successfully detected U1 snRNA mutation in five DNA samples and four RNA samples. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-25T16:54:51.453181+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000694","title":"IL-27 promotes tumour control by enhancing cytotoxic T cell function","description":"Cytotoxic CD8+ T lymphocytes (CTL) are essential for anti-tumour immunity but are frequently dysfunctional in established tumours. Here, we show that expression of a CTL signature is strongly associated with IL-27 expression in diverse human and murine tumours. In mice, IL-27 acts directly on tumour-specific CTL to promote their persistence and effector function in the tumor microenvironment. Moreover, treatment with inducible IL-27 overexpression or a half-life-extended IL-27 protein in vivo is well tolerated, induces regression of large established tumours, drives an enhanced cytotoxic program in anti-tumour CTL, and synergizes with PD-L1 blockade. In cancer patients treated with anti-PD-1 or anti-PD-L1 therapy, high expression of IL-27 is associated with improved clinical response. Finally, IL-27 increases cytotoxicity and limits terminal differentiation of human CD8+ T cells during chronic antigen exposure. Our data demonstrate that endogenous IL-27 is essential for anti-tumour immunity and that IL-27 receptor agonism can safely improve anti-tumor T cell responses alone or in combination with PD-L1 blockade.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-30T13:45:42.887681+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000695","title":"Genome-wide NanoRCS of cfDNA from plasma of healthy individuals","description":"Levels of circulating tumor DNA (ctDNA) in liquid biopsies may serve as a sensitive biomarker for real-time, minimally-invasive tumor diagnostics and monitoring. However, detecting ctDNA is challenging, as much fewer than 5% of the cell-free DNA in the blood typically originates from the tumor. To detect lowly abundant molecules, extremely sensitive sequencing methods are required. We adapted a new technique, NanoRCS, which is based on Oxford Nanopore sequencing of concatenated copies of a single DNA molecule for genome-wide sequencing, and applied this to plasma of healthy controls.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-09T12:57:49.949457+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000696","title":"Single-cell whole genome sequencing data of Pediatric B-cell Acute Lymphoblastic Leukemia","description":"Single-cell whole genome sequencing data of Minimal Residual Disease cells in Pediatric B-cell Acute Lymphoblastic Leukemia","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000697","title":"Heterogeneous endocrine cell composition defines human islet functional phenotypes","description":"Phenotyping and genotyping initiatives within the Integrated Islet Distribution Program (IIDP), the largest source of human islets for research in the U.S., provide standardized assessment of islet preparations distributed to researchers and enable the integration of multiple data types. Data from islets of the first 299 organ donors without diabetes analyzed using this pipeline highlights substantial heterogeneity in islet cell composition associated with hormone secretory traits, sex, reported race and ethnicity, genetically predicted ancestry, and genetic risk for type 2 diabetes (T2D). While α and β cell composition influenced insulin and glucagon secretory traits, the abundance of δ cells showed the strongest association with insulin secretion and was also associated with the genetic risk score (GRS) for T2D. These findings have important implications for understanding mechanisms underlying diabetes heterogeneity and islet dysfunction and may provide insight into strategies for personalized medicine and β cell replacement therapy.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-02T10:35:44.461757+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000698","title":"Multiplexing cortical brain organoids for the longitudinal dissection of developmental traits at single cell resolution","description":"Dissecting human neurobiology at high resolution and with mechanistic precision requires a major leap in scalability, given the need for experimental designs to multiple individuals and, prospectively, population cohorts. To lay the foundation for this, we have implemented and benchmarked complementary strategies to multiplex brain organoids by pooling cells from different pluripotent stem cell lines (PSC) either during organoid generation (mosaic models) or before single cell-RNAseq library preparation (downstream multiplexing). We have also developed a new computational method, SCanSNP, and a consensus call to deconvolve cell identities, overcoming current criticalities in doublets prediction and low quality cells identification. We validated both multiplexing methods for charting neurodevelopmental trajectories at high resolution, thus linking specificity to genetic variation. Finally, we modelled their scalability across different multiplexing combinations and showed that mosaic organoids represent an enabling method for high-throughput settings. Together, this multiplexing suite of experimental and computational methods provides a highly scalable  resource for disease modelling.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000699","title":"Development of targeted DNA sequencing panel for brain tumors","description":"A prompt and reliable molecular diagnosis for brain tumors has become crucial in precision medicine. While Comprehensive Genomic Profiling (CGP) has become feasible, there remains room for enhancement in brain tumor diagnosis due to the partial lack of essential genes and limitations in broad copy number analysis. In addition, the long turnaround time of commercially available CGPs poses an additional obstacle to the timely implementation of results in clinics. To address these challenges, we developed a CGP encompassing 113 genes, genome-wide copy number changes, and MGMT promoter methylation. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[38332448],"external_links":null,"is_released":true,"released_date":"2024-11-26T08:05:54.086312+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000700","title":"Targeted pancancer RNA-Seq","description":"This dataset contains targeted RNA-Seq generated with the Illumina RNA Pan-Cancer panel. It comprises 2200 cancers from children and adults. The cancers represent a wide range of CNS, solid and haematopoeitic tumours. Samples are from pathology specimens including FFPE, fresh frozen, bone marrow aspirate and peripheral blood.The data is used for tumour driver identification. SNVs, indels and fusion detection.\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-15T13:35:41.105383+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000701","title":"Use of new methodologies to achieve a thorough molecular characterization in pediatric acute leukemia","description":"In childhood leukemia, a better genetic characterization is needed to define new clinic-biological entities, refine the risk-stratification of patients and help to reduce the toxicity by applying a risk-directed therapy. This project aims to obtain information that will allow us to personalize the management of pediatric patients with leukemia as much as possible, so that we can offer a complete diagnosis, a sensitive follow-up and a more targeted treatment to the real risk of each case. The use of massive genome analysis technologies such as transcriptome sequencing (RNA-Sequencing) will allow a comprehensive biological characterization of pediatric leukemia patients, especially those cases that we have not been able to characterize by conventional diagnostic techniques. We believe that the RNA-Seq technique will allow us to identify new biomarkers that will be useful for: 1) defining new biological entities with their own clinical behavior; 2) refining the stratification of patients into risk groups; 3) finding targets for a better follow-up of MRD and 4) identifying therapeutic targets for the application of targeted therapies to reduce toxicity.\r\n\r\nPI: Camós-Guijosa, Mireia; Vega-García, Nerea\r\nFunding: PI21/00213 Instituto de Salud Carlos III (ISCIII)","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-14T13:36:57.710697+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000702","title":"SAPCS Blood RNA-seq of prostate cancer patients","description":"The study aims to quantify the gene expression in blood samples in 20 prostate cancer patients under the Southern African Prostate Cancer Study (SAPCS). The objective is to identify a list of differentially expressed genes.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-11-29T10:01:37.724852+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000703","title":"Evidence for Enhancer Activity in Intron 1 of TNFRSF1A Using CRISPR/Cas9 in Human Induced Pluripotent Stem Cell-derived Macrophages","description":"Use of CRISPR/Cas9 technology to study the TNFRSF1A gene, which plays a key role in autoimmune diseases such as \r\nankylosing spondylitis, multiple sclerosis, and inflammatory bowel disease. By editing a specific regulatory element within \r\nthe TNFRSF1A locus, we have identified the role of an enhancer element that is not well understood.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-19T14:31:14.803478+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000704","title":"WES of der(1;7)(q10;p10) myeloid neoplasms","description":"The study examined WES of der(1;7)(q10;p10) myeloid neoplasm cases. BAM files of WES of 26 myeloid neoplasm patients with der(1;7)(q10;p10) were used to identify key driver genes in patients with der(1;7)(q10;p10). This study is one of the largest WES for der(1;7)(q10;p10)(+) myeloid neoplasm cases.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-08T16:01:58.356787+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000705","title":"RNA-seq of der(1;7)(q10;p10) & control MDS patients","description":"The study examined the RNA profiles of MDS cases. This study utilized BAM files of RNA-seq of der(1;7)(q10;p10) MDS cases, -7/del(7q) MDS cases, and OTHER MDS cases to analyze gene expression. In particular, the study profiled der(1;7)(q10;p10) MDS cases compared to non-der(1;7)(q10;p10) MDS cases. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-08T16:01:54.098413+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000706","title":"Epstein-Barr Virus status drives morphological and molecular intra-tumour heterogeneity in gastric cancer: insights from a case report and literature review","description":"This case report describes a rare case of bi-phenotypic gastric cancer with two distinct, but clonally related, histological components. The first component, associated with Epstein-Barr virus (EBV) infection, exhibited the morphological features of gastric carcinoma with lymphoid stroma, suggesting that EBV, as an effective immunogenic factor, may trigger a prominent immune response within the tumour microenvironment. The second component, which was EBV-negative, displayed tubular/papillary morphology and features of increased biological aggressiveness, such as high-grade areas and lymphatic invasion. Immunohistochemical and molecular studies confirmed that, despite the differing morphologies and immunophenotypes, both components were clonally related, with especially the EBV-negative area showing more complex DNA aberrations, reminiscent of Chromosomally instable (CIN) lesions. This case describes clonally related EBV-positive and negative components within a single gastric cancer, contributing to a better understanding of EBV role in tumour heterogeneity and progression and highlighting the impact of EBV loss on tumour behaviour.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-02T17:37:09.805185+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000707","title":"Complement C1s deficiency in a male Caucasian patient with systemic lupus erythematosus: A case report","description":"This study involves whole genome sequencing of a 34-year-old male with a rare deficiency in complement component C1s, linked to systemic lupus erythematosus (SLE). Genomic analysis revealed two novel mutations in the C1S gene, resulting in absent C1s protein and impaired classical complement pathway function. The goal was to confirm the C1s deficiency and identify the specific mutations causing this condition.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[38469558],"external_links":null,"is_released":true,"released_date":"2024-12-03T10:42:05.838528+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000708","title":"Saliva Microbiota of Finnish children from the PANIC study","description":"Saliva Microbiota of Finnish children aged between 6-8 yrs in the PANIC study. Baseline data. Studied for various lifestyle conditions and oral diseases (without caries/with caries).","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-10T11:54:11.892542+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000709","title":"Convergent evolution towards CD38 biallelic loss is a recurrent mechanism of resistance to anti-CD38 antibodies in multiple myeloma.","description":"Monoclonal antibodies directed against CD38 are a therapeutic mainstay in multiple myeloma (MM). While they have contributed to improved outcomes, most patients will still experience disease relapse. Despite their ubiquity, little is known about tumor-intrinsic mechanisms of resistance to these drugs. Antigen escape, whereby tumor cells alter expression of cell surface immunotherapy targets, has been proposed as a potential avenue, and has been seen with other immunotherapies in MM. Yet, it is unknown whether MM cells can develop permanent resistance to anti-CD38 antibodies by acquiring genomic events leading to biallelic disruption of the CD38 gene locus. Here, by using whole genome and whole exome sequencing data from 701 newly diagnosed patients, 72 patients at relapse with naivety to anti-CD38 antibodies,  and 52 patients collected at relapse following anti-CD38 antibodies, we report biallelic inactivation of CD38 as a recurrent mechanism of resistance in 6% of patients, often via convergent evolution where distinct subclones are advantaged towards the same selective endpoint within the same patient. Monoallelic loss of the CD38 locus was seen in another 14% post-CD38-directed therapy.  Three of the cases with biallelic events on CD38 presented with missense mutations and retained CD38 expression. Functional work demonstrated that two of these mutations decreased binding affinity and antibody-dependent cellular cytotoxicity of commercial antibodies Daratumumab and Isatuximab. However, the third mutation (R140G) provided relative resistance only towards one commercial product. Given that patients are often rechallenged with CD38 antibodies following disease progression, these data support the need for next generation sequencing to guide treatment selection.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000710","title":"Phase 1/2 Study of the Indoleamine 2,3-Dioxygenase 1 Inhibitor Linrodostat Mesylate Combined With Nivolumab or Nivolumab and Ipilimumab in Advanced Solid Tumors or Hematologic Malignancies","description":"Purpose: To evaluate the safety, efficacy, pharmacokinetics, pharmacodynamics, and biomarker data of linrodostat mesylate, a selective, oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, combined with nivolumab ± ipilimumab in advanced solid tumors and hematologic malignancies.\r\nPatients and Methods: In this phase 1/2 study, patients received once-daily (QD) linrodostat (part 1 [escalation], 25-400 mg; part 2 [expansion], 100 or 200 mg) plus nivolumab (480 mg every [Q] 4 weeks [W] or 240 mg Q2W) or triplet therapy (part 3, linrodostat 20-100 mg QD; nivolumab 360 mg Q3W or 480 mg Q4W; ipilimumab 1 mg/kg Q6W or Q8W). Endpoints included safety and efficacy (co-primary; parts 2, 3), pharmacokinetics, pharmacodynamics, biomarkers, and efficacy (part 1). \r\nResults: Fifty-five, 494, and 41 patients were enrolled in parts 1, 2, and 3, respectively. Linrodostat exposures exceeded predicted therapeutic target concentrations starting at 50 mg. Rates of grade 3/4 adverse events were 50.1%-63.4%. The maximum tolerated linrodostat dose was 200 mg; dose-limiting toxicities were primarily immune related. Responses were observed across different cohorts, study parts, and tumor types, particularly in immunotherapy-naive patients. Kynurenine decreased with linrodostat + nivolumab, regardless of response. In contrast, interferon gamma (IFN-γ) gene expression signature was associated with response; in nonmelanoma patients, a composite of low tryptophan 2,3-dioxygenase (TDO2) gene expression plus high IFN-γ signature was associated with response. \r\nConclusions: Linrodostat + nivolumab ± ipilimumab demonstrated a manageable safety profile. Kynurenine changes supported IDO1 pathway inhibition but did not correlate with response. A composite biomarker of low TDO2 expression plus high IFN-γ gene expression may predict response to linrodostat + nivolumab. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-09T12:55:19.991834+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000711","title":"SALTO: chromosomal copy number alterations to predict response to bevacizumab","description":"Study of the correlation between vessel formation and or CMS subtypes in relation to a predictive copy number marker for bevacizumab. Shallow Whole Genome Sequencing of 92 mCRC samples.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-18T11:10:22.042767+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000712","title":"25 ulcerative colitis patient before and 14 weeks after the initiation of vedolizumab therapy","description":"25 ulcerative colitis patient before and 14 weeks after the initiation of vedolizumab therapy were collected, single cell RNA sequencing of gut mucosal and peripheral blood cells were performed.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000713","title":"single cell RNA sequencing of PSC-IBD and UC patient","description":"Forty-seven colonic mucosal biopsies of PSC-IBD (n=24), UC (n=18) (where possible matched inflamed (I) non-inflamed (NI)), and non-IBD subjects (n=5) were collected and dissociated. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000714","title":"Molecular correlates for HPV-negative head and neck cancer engraftment prognosticate patient outcomes","description":"Head and neck squamous cell carcinoma (HNSCC) tumors were sampled from 88 patients. Samples were implanted subcutaenously into the flank of NOD/SCID/IL2R-/- mice. Mice were then monitored weekly for tumor growth and the time of initial palpation was recorded. Mice were euthanized when tumors reached 15 mm in diameter or after 6 months. If no tumor formed by 6 months, the patient tumor was defined as Non-engrafter (N). RNA-seq was performed on all primary tumor samples and successfully engrafted patient-derived xenograft (PDX) samples.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-02-18T18:43:08.599433+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000715","title":"Multimodal cell-free DNA whole-genome TAPS is sensitive and reveals specific cancer signals","description":"This study presents a methodology for detecting circulating tumor DNA (ctDNA) using deep whole-genome TET-Assisted Pyridine Borane Sequencing (TAPS), a less destructive alternative to bisulphite sequencing. The method enables simultaneous analysis of genomic and methylomic data for multi-cancer detection and monitoring minimal residual disease. In a diagnostic accuracy study across various cancer types, it achieved 85.3% sensitivity and 88.8% specificity, with validation done using matched tumour biopsies. Additionally, in silico validation showed strong discrimination at low ctDNA levels. The approach also successfully tracks tumour burden and ctDNA shedding from precancerous lesions post-treatment, making it ready for further clinical testing.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-20T17:39:20.595848+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000716","title":"Studying the cellular diversity of the human hypothalamus","description":"We use single-cell and spatial transcriptomics to catalogue cellular populations and their locations in the human hypothalamus","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-02-03T11:28:55.268477+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000717","title":"Duplex sequencing","description":"We performed duplex sequencing on buccal mucosa samples (20, 28, and 254 mm^2 swabs) and esophageal samples (10 mm^2) obtained from 10 subjects.","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-02T16:47:08.671801+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000718","title":"NanoSeq","description":"We performed NanoSeq on buccal mucosal samples. We used 28 mm^2 swab DNA as samples and 254 mm^2 swab DNA as controls.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-02T16:47:09.948494+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000719","title":"Clinical evaluation of long read sequencing-based episignature detection in developmental disorders","description":"Some developmental disorders (DD) are marked by specific genome-wide methylation changes, known as episignatures, which can support diagnosis and reveal underlying mechanisms. Current methods rely on indirect methylation profiling. Here, we assessed whether long-read whole genome sequencing with nanopore technology could directly detect both episignatures and genetic variants. We sequenced forty controls and twenty DD patients, using clustering and dimensional reduction to compare methylome patterns with microarray-based signatures. Our classifiers accurately identified episignatures in 17 of 19 patients with pathogenic variants, matching microarray results. This study shows nanopore sequencing enables comprehensive, haplotype-aware genomic and epigenomic analysis for DD diagnostics.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-03T09:27:50.697784+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000720","title":"A single-cell atlas of the early COPD lung","description":"Single cell atlas of the human airways from 10 patients suffering of early stage Chronic Obstructive Pulmonary Disease and 12 healthy age matched volunteers. This dataset was sequenced by 10X Genomics 3’ RNA-seq profiling. It is composed of more than 400 000 cells coming from 119 samples total. Sampling was performed by brushings and biopsies from the nose to the 6 th division of the airways.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-06T15:18:08.473053+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000721","title":"eQTL analysis in 27 sorted circulating immune cell types","description":"eQTL analysis of bulk messenger RNA sequencing data of 27 sorted circulating immune cell populations collected from ~200 human healthy donors and their genomic DNA genotypes.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000722","title":"Single-cell RNA-Seq of healthy human intestine","description":"Single-cell RNA sequencing data of human intestine in three anatomical locations (terminal ileum, transverse colon, rectum) collected from 60 healthy donors using 10X Genomics 3' GEM kit.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-12T14:57:36.613824+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000723","title":"WGS of CTCs enriched using high-throughout microfluidic device from entire cancer patient leukopak","description":"Single-cell low-pass WGS analysis (illumina platform, PE150, 1-2x coverage) was performed on CTCs enriched using high-throughout microfluidic device from entire leukopak from patients with metastatic prostate cancer (GU-1 and GU-2) and metastatic hepatocellular carcinoma (HCC-1 and HCC-2). ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-09T17:07:58.718527+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000724","title":"WES for CNV-verified CTCs enriched by high-throughout microfluidic device from entire cancer patient leukopak","description":"WES analysis (illumina platform, PE150, 100x coverage) was performed on a pool of copy number variation (CNV)-verified CTCs that were enriched using high-throughout microfluidic device from entire leukopak from patients with metastatic prostate cancer (GU-1 and GU-2). ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-09T17:07:57.458846+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000725","title":"FOCUS Trial","description":"We studied patients with advanced colorectal cancer, starting treatment with non-curative intent. 2135 unpretreated patients were randomly assigned to three treatment strategies in the ratio 1:1:1. Strategy A (control group) was single-agent fl uorouracil (given with levofolinate over 48 h every 2 weeks) until failure, then single-agent irinotecan. Strategy B was fl uorouracil until failure, then combination chemotherapy. Strategy C was combination chemotherapy from the outset.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[17630037],"external_links":null,"is_released":true,"released_date":"2024-12-12T16:32:08.010697+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000726","title":"Distinct immune cell infiltration patterns in PDAC exhibit divergent immune cell selection and immunosuppressive mechanisms","description":"Pancreatic ductal adenocarcinoma has a dismal prognosis. A comprehensive analysis of single-cell multi-omic data from matched tumour-infiltrated CD45+ cells and peripheral blood in 12 patients, and two published datasets, reveals a complex immune infiltrate. Patients have either a myeloid-enriched or adaptive-enriched tumour microenvironment. Lymphocyte enrichment is intrinsically linked with highly distinct B and T cell clonal selection, diversification, and differentiation. Using TCR data, we see the largest clonal expansions in CD8 effector memory, senescent cells, and highly activated regulatory T cells which are induced within the tumour from naïve cells. We identify pathways that potentially lead to a suppressive microenvironement, including targets of immunotherapy and checkpoints including TIGIT/PVR and SIRPA/CD47. PDAC patient tumors from the APACT clinical trial revealed that patients with myeloid enrichment had the shorter overall survival compared to those adaptive cell enrichment. We identify multiple therapeutic targets that should form the basis for rational design including boosting of B cell responses, targeting immunosuppressive macrophages, and specific Treg depletion approaches. The dataset is scRNA-seq data from PDAC patients.\r\n\r\n","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-09T11:59:21.09141+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000727","title":"DNA methylation data of High Grade Serous Ovarian Cancer Patients","description":"This study contains DNA methylation data derived from longitudinal tissue samples of High Grade Serous Ovarian Cancer (HGSC) patients belonging to the DECIDER study (NCT04846933). Ovarian cancer kills more than 40 000 women in Europe each year, and HGSC is the most common and most difficult to treat subtype of this disease. This study contains different whole-genome bisulfite sequencing (WGBS) datasets with samples from different stages during the treatment of the patients.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000728","title":"RNAseq samples of patients with anti-PD-1 resistant HNSCC from a non-randomized, open-label phase 1b clinical trial","description":"Immune checkpoint blockade (ICB) is an effective treatment for a subset of patients with head and neck squamous cell carcinoma (HNSCC); however, the majority remain refractory. In a nonrandomized, open-label Phase 1b clinical trial, participants with recurrent and/or metastatic (R/M) HNSCC who had progressed on ICB were treated with low-dose 5-azacytidine (5-aza) daily for either 5 or 10 days, in combination with durvalumab and tremelimumab. The primary objective was to determine the biologically effective dose of 5-aza. In this study, RNA sequencing (RNA-seq) was performed on baseline and on-treatment samples from eight participants, and transcriptomic changes were analyzed to assess the impact of low-dose 5-aza treatment.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-12T14:42:15.796584+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000729","title":"WES samples of patients with anti-PD-1 resistant HNSCC from a non-randomized, open-label phase 1b clinical trial","description":"Immune checkpoint blockade (ICB) is an effective treatment for a subset of patients with head and neck squamous cell carcinoma (HNSCC); however, the majority remain refractory. In a nonrandomized, open-label Phase 1b clinical trial, participants with recurrent and/or metastatic (R/M) HNSCC who had progressed on ICB were treated with low-dose 5-azacytidine (5-aza) daily for either 5 or 10 days, in combination with durvalumab and tremelimumab. The primary objective was to determine the biologically effective dose of 5-aza. In this study, whole exome sequencing (WES) was performed on baseline samples from 12 participants, and genomic alterations were analyzed to access the genetic background of these participants.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-12T14:42:18.712703+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000730","title":"Brazilian Genomes","description":"We generated 2,702 high-coverage whole-genome sequences of Brazilian population from the country’s five geographical regions. This diverse group encompasses individuals from urban and rural settings (including riverine communities) and represents various ethnic backgrounds, including Afro-Brazilians.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-12T09:18:48.919323+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000731","title":"PEVOsq","description":"The PEVOData PEVOsq basket trial is an open-label, multi-center, phase II trial investigating the combination of pembrolizumab (an immune checkpoint inhibitor) with vorinostat (a histone deacetylase inhibitor). This trial focuses on treating patients with recurrent or metastatic squamous carcinomas, including cancers of the cervix, head and neck, anus, vulva/vagina, penis, and lung. The aim is to evaluate the efficacy and safety of this combination, with pembrolizumab administered every 3 weeks and vorinostat daily. Outcomes include overall response rate and progression-free survival.  ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-20T15:53:23.275867+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000732","title":"ICARUS-LUNG01-RNAseq","description":"Bulk RNA-seq was carried out on 20 pairs of frozen tumor biopsies. Differential gene expression (DGE) analyses was conducted, looking at the fold change of gene expression of matched on-T/BL samples in the overall population and, then, separately in responders and non-responders.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-12T16:04:32.192299+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000733","title":"ICARUS-LUNG01-ExomeSeq","description":"Whole exome sequencing (WES) on frozen tumor biopsies at BL to identify genomic alterations associated with response/resistance. Non-\r\nsynonymous point mutations, indels, homozygous deletions, loss of heterozygosity (LOH) and low, medium, and high-level amplifications were assessed.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-12T16:04:32.192299+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000734","title":"Molecular counting enables accurate and precise quantification of methylated ctDNA for tumor-naive cancer therapy response monitoring","description":"Personalized cancer treatment can significantly extend survival and improve quality of life for many patients, but accurate and real-time therapy response monitoring remains challenging. To overcome logistical and technical challenges associated with therapy response monitoring via imaging scans or assays that track the variant allele fraction (VAF) of somatic mutations in circulating tumor DNA (ctDNA), we developed a tumor-naive liquid biopsy assay that leverages Quantitative Counting Template (QCT) technology to accurately and precisely quantify methylated ctDNA (Northstar ResponseTM).","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-12T11:08:13.08268+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000735","title":"Single-Cell Profiling of the Human Endometrium in Polycystic Ovary Syndrome: Uncovering Disease Signatures and Treatment Responses","description":"We generated the first single-nuclei map of human endometrial biopsies from women with and without PCOS to identify cell-type-specific disease signatures, compositional variations, and transcriptomic reversibility after a 16-week intervention with metformin or lifestyle. Single nuclei were extracted from 27 frozen endometrial biopsies for snRNA-seq using the 10X Genomics protocol. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-07T16:30:54.170911+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000736","title":"Whole-exome sequencing profiling of patients with metastatic prostate cancer at VHIO","description":"Metastatic prostate cancer (mPC) is enriched for homologous recombination repair (HRR) gene alterations, which have prognostic and predictive value. Routine clinical implementation of next-generation sequencing (NGS) is still limited. We investigated the association between genomic and functional loss of HRR, using NGS and a RAD51 immunofluorescence (RAD51-IF) iprimary or metastatic biopsies from patients with stage IV prostate cancer.  Whole-exome sequencing was pursued for paired tumor-normal samples.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-13T10:24:22.089036+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000737","title":"Bulk-RNAseq from human nerve fascicles and Schwann cells","description":"Bulk-RNAsequencing from human nerve fascicles from patients with polyneuropathies, and human Schwann cell cultures isolated from said nerve fascicles, in comparison to control human Schwann cell cultures and a referential fibroblast culture. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-16T16:25:58.806644+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000738","title":"DNA methylation and transposable element landscapes define human regulatory T cells in tissues and identify their blood recirculating counterpart","description":"Regulatory T cells (Treg cells) in tissues can perform immunoregulatory and tissue-regenerative functions. Despite these important tasks, human-tissue Treg cells lack understanding, specifically, the epigenetic basis of their differentiation as well as re-circulating tissue-Treg cells are incompletely understood. Here, we performed genome-wide DNA methylation analysis of human Treg cells from skin and blood and embedded this in a multi-omic epigenetic framework including chromatin accessibility and gene-expression. We thereby revealed novel epigenetic programs defining human skin Treg cell differentiation and delineated how these are present on the different epigenetic levels. We discovered that transposable elements are an integral constituent of the demethylation landscape in skin Treg cells. Based on TCR-sequencing and DNA demethylation homologies, our data unveil that blood CCR8+ Treg cells are recirculatory human tissue-Treg cells. Our data provide novel insights in human tissue-Treg biology, required to harness these cells for therapeutic avenues. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[40670618],"external_links":null,"is_released":true,"released_date":"2025-06-06T16:17:31.268244+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000739","title":"Single cell sequencing data of PBMC and CSF from a cohort of Multiple Sclerosis patients and other neurological disease controls","description":"Neuroinflammation is often characterised by immune cell infiltrates in the cerebrospinal fluid (CSF). Here we apply single-cell RNA sequencing to explore the functional characteristics of these cells in patients with various inflammatory, infectious and non-inflammatory neurological disorders. We show that CSF is distinct from the peripheral blood in terms of both cellular composition and gene expression. We report that the cellular and transcriptional landscape of CSF is altered in neuroinflammation, but is strikingly similar across different neuroinflammatory disorders. We find clonal expansion of CSF B and T cells in all disorders but most pronounced in inflammatory diseases, and we functionally characterise the transcriptional features of these cells. Finally, we explore the genetic control of gene expression in CSF lymphocytes. Our results highlight the common features of immune cells in the CSF compartment across diverse neurological diseases and may help to identify new targets for drug development or repurposing in Multiple Sclerosis.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-08T16:58:13.090487+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000740","title":"Single individual whole genome sequencing of Jakun, Indigenous Peoples of the Peninsular Malaysia","description":"This study disected the genetic structure of a Jakun individual, a sub-tribe of Indigenous Proto-Malay from Peninsular Malaysia. They are postulated to have settled in Peninsular Malaysia approximately 4-6 KYA, during the last agricultural expansion. However, their genetic structure is still not well understood.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-13T10:18:22.605223+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000741","title":"MIBC NAC2020 cohort RNA sequencing","description":"The dataset contains RNA sequencing data from N=48 transurethral resections of bladder tumours (TURBTs) from N=48 patients with muscle-invasive bladder cancer. All TURBTs originate from formalin-fixed paraffin embedded tissue. We used the Illumina TruSeq RNA exome kit, previously known as the TruSeq RNA Access Library Prep Kit. This kit converts total RNA into template molecules of known strand origin, followed by sequence-specific capture of coding RNA. All samples were run in an Illumina NovaSeq6000 instrument. Paired FASTQ files from all 48 patients are provided.\r\n\r\n","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-16T15:43:51.703506+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000742","title":"WGS data for EBiSC iPSC lines ","description":"The European Bank for Induced Pluripotent stem cells (EBiSC) is designed to address the increasing demand by iPSC researchers for quality-controlled, disease-relevant research grade iPSC lines, data and cell services. In this study Whole Genome Sequencing was performed on a selection of lines from the project.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-17T12:06:24.620156+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000743","title":"Pyjacker identifies enhancer hijacking events in acute myeloid leukemia including MNX1 activation via deletion 7q","description":"Acute myeloid leukemia with complex karyotype (ckAML) is characterized by high genomic complexity, including frequent TP53 mutations and chromothripsis. We hypothesized that the numerous genomic rearrangements could reposition active enhancers near proto-oncogenes, leading to their aberrant expression. We developed pyjacker, a computational tool for the detection of enhancer hijacking events, and applied it to a cohort of 39 ckAML samples. Pyjacker identified motor neuron and pancreas homeobox 1 (MNX1), a gene aberrantly expressed in 1.4% of AML patients, often as a result of del(7)(q22q36) associated with hijacking of a CDK6 enhancer. MNX1-activated cases show significant co-occurrence with BCOR mutations and a gene signature shared with t(7;12)(q36;p13) pediatric AML. We demonstrated that MNX1 is a dependency gene, as its knockdown in a xenograft model reduces leukemia cell fitness. In conclusion, enhancer hijacking is a frequent mechanism for oncogene activation in AML.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-18T14:09:58.816579+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000744","title":"MET amplification in gastric cancer","description":"Targeting MET in gastric and gastroesophageal junction adenocarcinoma (GC) with monoclonal antibodies or tyrosine kinase inhibitors has had limited success. We hypothesize that other prognostic and response determining genetic alterations explain the poor outcome and lack of response to MET-targeted therapies.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-27T11:19:20.10032+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000745","title":"Spermidine/spermine N1-acetyltransferase controls tissue-specific  regulatory T cell function in chronic inflammation","description":"In this project we wanted to understand the role of tissue resident regulatory T cells with the aim of finding commonalities between multiple inflammatory diseases namely psoriasis, sarcoidosis and inflammatory bowel disease.  Using single cell sequencing data we found that specifically in the skin, Spermidine/spermin N1-acetyltransferase seems to mediate a „fragile“ Treg phenotype. To test the influence of the tissue on this phenotype we also sought to charactierize a similar population in patient PBMCs for which we generated this data.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-19T17:55:57.047566+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000746","title":"The genetic footprint of the European Roma diaspora: Evidence from the Balkans to the Iberian Peninsula","description":"Our genomic approach focuses on: (i) the internal genetic structure of Roma and its correlation with geography; (ii) the relationships between Iberian Roma and other non-Roma populations to explore possible contacts during the period of population upheaval following the Roma’s arrival on the Iberian Peninsula; (iii) estimation of the admixture events in the Iberian Roma before and after their arrival to the Iberian Peninsula; and (iv) the assessment of endogamy patterns and assortative mating of the European Roma. Our study provides a detailed analysis of the intricate population history of the Iberian Roma, offering insights from both micro-geographical and large-scale perspectives on the population history of European Roma.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-23T16:56:16.570677+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000747","title":"Nivolumab plus chemotherapy or ipilimumab in gastroesophageal cancer: CheckMate 649 biomarker analyses","description":"First-line nivolumab-plus-chemotherapy demonstrated superior overall survival (OS) versus chemotherapy for advanced gastroesophageal adenocarcinoma (CheckMate 649). Nivolumab-plus-ipilimumab provided durable responses and higher survival rates versus chemotherapy; however, the prespecified OS significance boundary was not met. To identify biomarkers predictive of differential efficacy outcomes, exploratory analyses were performed using whole-exome sequencing and RNA sequencing. Nivolumab-based therapies demonstrated improved efficacy versus chemotherapy in hypermutated and, to a lesser degree, Epstein Bar Virus-positive tumors compared with chromosomally unstable and genomically stable tumors. Within the KRAS-altered subgroup, only patients treated with nivolumab-plus-chemotherapy demonstrated improved OS benefit versus chemotherapy. Low stroma gene expression signature scores were associated with OS benefit with nivolumab-based regimens; high regulatory T-cell signatures were associated with OS benefit only with nivolumab-plus-ipilimumab. Our analyses suggest that distinct and overlapping pathways contribute to the efficacy of nivolumab-based regimens in gastroesophageal adenocarcinoma.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-12T09:58:43.341058+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000748","title":"Submission 6 - study_title 1 - edited","description":"Submission 6 - description 1 -edited","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000749","title":"Submission 6 - study_title 2 - edited","description":"Submission 6 - description 2 - edited","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000750","title":"Human scMultiome data (GEX and ATAC paired) from CD34+ Bone Marrow (BM) and mobilized peripheral blood (mPB), including CITE-Seq data from mPB CD34+ samples","description":"We analyzed healthy CD34+ samples from Bone Marrow (BM) and mobilized Peripheral Blood (mPB) in gene therapy experiments within the X-PAND project. BM samples underwent scMultiome analysis, providing paired GEX and ATAC data. For the mPB samples, both scMultiome and CITE-Seq were performed on the same donors, offering additional protein marker information. These datasets allow for an in-depth exploration of chromatin accessibility, gene expression, and surface protein profiling in hematopoietic progenitor cells from healthy donors.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-08T15:14:38.813137+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000751","title":"Bulk and single-cell RNA-sequencing data from five lines of human iPSC-derived (hiPSC-derived) astrocytes (3 in-house and 2 commercial lines), both alone and in co-culture with neurons, to define the molecular response of astrocytes to misfolded alpha-synuclein","description":"RNA editing is a post transcriptional mechanism that targets changes in RNA transcripts to modulate innate immune responses. We report the role of astrocyte specific, ADAR1 mediated RNA editing in neuroinflammation in Parkinson’s disease. We generated hiPSC-derived astrocytes, neurons and co-cultures and exposed them to small soluble alpha-synuclein aggregates. Oligomeric alpha-synuclein triggered an inflammatory glial state associated with TLR activation, viral responses,  and cytokine secretion. This reactive state resulted in loss of neurosupportive functions, and the induction of neuronal toxicity. Notably, interferon response pathways were activated leading to upregulation, and isoform switching of the RNA deaminase enzyme, ADAR1. ADAR1 mediates A-to-I RNA editing, and increases in RNA editing were observed in inflammatory pathways in cells, as well as in post-mortem human PD brain. Aberrant, or dysregulated, ADAR1 responses and RNA editing may lead to sustained inflammatory reactive states in astrocytes triggered by alpha-synuclein aggregation, and this may drive the neuroinflammatory cascade in Parkinson’s.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-24T15:50:16.908412+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000752","title":"Diagnostic Genomic Analysis is Prognostic in AYA ALL Patients Treated on a MRD-Stratified Paediatric Protocol","description":"Background: Over the last decade, next generation sequencing has enabled classification of multiple new recurrent genomic drivers of acute lymphoblastic leukemia (ALL). We provide a comprehensive genomic survey of adolescent and young adult (AYA) patients treated on the Australasian Leukaemia and Lymphoma Group (ALLG) ALL06 study. ALL06 clinical trial described the efficacy and tolerability of AYA ALL patients aged 15-39 years treated on a single minimal residual disease (MRD)-stratified platform. In this study we have taken the ALL06 cohort and retrospectively performed comprehensive genomic analyses assessing response of AYA patients with various genomic subtypes treated with a paediatric approach. Methods: Genomic risk classification of B- and T-ALL patients (n=57) enrolled to the study was based on mRNA-Sequencing, MLPA, immunophenotyping and cytogenetics. Results: Using this approach, 36/40 (90%) B- and 13/17 (76.5%) T-ALL patients were classified according to genomic risk. We have linked outcome data with each patient’s genomic risk and found a strong correlation between adverse genomic risk and MRD at the end of consolidation, translating to inferior overall and relapse free survival. Patients with adverse risk genomics who achieved negative MRD status had improved responses compared to those with persistent MRD. Patients with standard risk genomics had excellent responses regardless of their MRD status. Conclusion: Our data argue strongly for incorporation of a genomic risk classification into future ALL treatment paradigms at the time of diagnosis.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-30T13:43:46.276526+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000753","title":"Anti-myeloperoxidase IgM B cells in anti-neutrophil cytoplasmic antibody-associated vasculitis ","description":"Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a prototypic autoimmune disease, with a subset of AAV patients manifesting anti-myeloperoxidase (MPO) IgG. Patients with AAV respond positively to B cell-targeting and complement-targeting therapies, but disease flares are not uncommon. Here, by comparing samples from healthy individuals and MPO+ AVV patients, we show that B cell autoreactivity against MPO in the circulation of patients is dominated by CD27+IgM+ B cells whereas MPO-specific IgG+ cells are infrequent. Additionally, while naive anti-MPO-IgM B cells are present in both patients and controls and produce anti-MPO IgM upon stimulation, anti-MPO-IgM memory B cells and serum anti-MPO IgM are features of patients. Our results thus hint that defective elimination of B cell reactivity to MPO in the human repertoire, the presence of activated IgM+ anti-MPO B cells in disease, and a dominant role for anti-MPO IgM in complement activation, may all contribute to MPO+ AAV etiology and thereby serve as potential target for therapy.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-03T10:32:58.960128+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000754","title":"Understanding Rare Variant Contributions to autism: Lessons from Dystrofin-Deficient Model","description":"This project generated a whole-exome sequencing (WES) dataset of 83 boys with a pathogenic variant in the DMD gene, along with WES data from the parents of 38 of them, totaling 159 samples. Pathogenic DMD variants, besides causing dystrophinopathies, are also known risk factors for neurodevelopmental disorders (NDDs). However, the low penetrance of NDDs in individuals with dystrophinopathies suggests that additional factors contribute to their manifestation. This study aimed to: (1) characterize ASD in males with dystrophinopathies; (2) determine the relevance of additional de novo and inherited rare risk variants for their neurodevelopmental phenotype; and (3) clinically and functionally characterize the identified risk variants.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-02-18T18:45:01.404278+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000755","title":"Transcriptome sequencing of HCC cells after ADRM1-Ex9 knockdown","description":"This dataset includes transcriptome sequencing data from the HCC cell line HKCI-10 following knockdown of the splicing variant ADRM1-Ex9. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000756","title":"Genetic coupling of enhancer activity and connectivity in gene expression control","description":"In this study, we investigated whether the genetic effects of eQTLs on enhancer activity and enhancer-promoter contacts (connectivity) are inherently coupled or distinct. To address this, we performed Capture Hi-C targeting ~1100 eQTL loci, along with ATAC-seq and RNA-seq, in monocytes from 34 healthy male donors. Using single-modality and multi-modality Bayesian statistical approaches, we demonstrated that eQTL effects are predominantly shared across enhancer activity, connectivity, and gene expression. However, we also identified a locus where an eQTL disrupts a CTCF binding site at a putative insulator, facilitating contacts between the PCK2 gene promoter and downstream enhancers. To validate these findings, we used 4C-seq to confirm the allelic effects of eQTLs on enhancer-promoter connectivity at the PCK2 locus and another eQTL region associated with THBS1 expression, both of which showed consistent eQTL effects across all three modalities. Additionally, we conducted Hi-C on monocytes from two donors to map reference TADs and performed ChIP-seq to confirm the allelic effects of the PCK2 eQTL on CTCF binding. Together, these data provide comprehensive insights into the genetic coupling of enhancer activity, connectivity, and gene expression.\r\n\r\n","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-23T16:59:28.770499+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000757","title":"Development of a fully human glioblastoma-in-brain-spheroid model for accelerated translational research","description":"In glioblastoma (GBM) the intricate interplay between tumor cells and the surrounding microenvironment plays a crucial role in tumor progression, invasion, and therapeutic resistance. So far, studying these interactions in a controlled and representative model system has been challenging. Here, we report the development of hGliCS, a human glioma-cortical spheroid model that allows the elucidation of the biology of GBM cells and their interactions with a human-specific brain-like microenvironment and neurons. GBM cells efficiently invade the cortical spheroids, forming a well-connected network of communicating cells. The heterogeneous cellular states of the GBM cells within this model closely resembled findings previously observed in glioblastoma patients and in mouse xenografts. We observed a transition from predominantly mesenchymal-like cells to heterotopic states with a high diversity. In contrast to the substantial changes observed in the tumor cell population, the impact of the GBM cells on the neurons was minimal. We further demonstrate the suitability of hGliCS to test compounds targeting tumor-specific neurobiological features.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-16T13:12:16.047066+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000758","title":"Multi-omics analysis reveals immune programs delineating disease severity in extrapulmonary tuberculosis","description":"This study investigates the immune response in extrapulmonary tuberculosis (EPTB) using single-cell RNA sequencing. Hierarchical clustering of patient transcriptomes identified three distinct levels of disease severity, uncovering immunological pathways involved in disease progression, including interferon and IL-1β-mediated signaling. The findings also led to the development of a diagnostic gene expression signature for both EPTB and pulmonary TB, offering potential improvements in TB diagnosis and treatment.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-30T12:51:24.039014+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000759","title":"The taxonomic composition of the human microbiome of CRC patients and healthy donors","description":"In this study, single homogenized human stool samples from five healthy donors and one CRC patient were analyzed by shotgun sequencing to generate a baseline for the establishment of humanized microbiome to be transferred into mice. Briefly, fecal DNA was isolated from these samples using the DNeasy PowerSoil DNA Isolation Kit (Qiagen), according to the kit manual, except that samples were homogenized using the TissueLyzerII for five minutes at 40Hz instead of intense vortexing. The extracted DNA was further purified and concentrated using the DNA Clean and Concentrator Kit (Zymo Research). This DNA was thawed and refrozen once at -80°C for 16s sequencing before being thawed again for WGS. 200 ng of DNA was used for metagenomic library preparation using the Next Generation Sequencing DNA Library Prep Kit (Westburg), according to the user manual using an average insert size of libraries of 450 base pairs. Following quantification and quality control (Qubit® dsDNA BR Assay Kit (Thermofisher Scientific); Bioanalyzer High Sensitivity DNA Analysis Kit (Agilent Technologies)), sequencing was performed on a NextSeq500 instrument using 2×150 base pair read lengths.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-03T10:29:02.269066+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000760","title":"A thymic ILC1-like progenitor with differentiation potential towards KIR+NKG2A- NK cells ","description":"KIR+NKG2A- Natural Killer (NK) cells have the unique ability to detect downregulation of single HLA-I allotypes, frequently occurring in malignantly-transformed and virus-infected cells in order to escape T cell recognition. We have recently shown that circulating Innate Lymphoid Cells 1 (cILC1) have the potential to generate such KIR+NKG2A- NK cells but their developmental origin was unknown. Here we demonstrate that the development of cILC1 is thymus-dependent and identify a putative progenitor of cILC1s in the thymus, called thyILC1. Single-cell RNAseq analysis revealed a close relationship of thyILC1s to CD34+ double-negative (DN) thymocytes, but in contrast to DNs, thyILC1s had lost T cell differentiation potential. However, like cILC1s they could be efficiently differentiated into KIR+NKG2A- NK cells. thyILC1s strongly expressed RAG1/2, PTCRA (preTCR, and NOTCH1/3, but lacked expression of TCR chains, suggesting that they failed to pass the -selection checkpoint of thymocyte development. Finally, analyses of patients with FOXN1het deficiency, showing thymic hypoplasia due to lack of mature thymic epithelial cells, exhibited a profound deficiency of cILC1s but not cILC2s and cILC3s, demonstrating thymus dependency of cILC1s. Together, the data suggest that thyILC1s are the source of a novel thymus-dependent NK cell differentiation pathway that promotes generation of KIR+NKG2A- NK cells.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-25T10:20:56.536605+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000761","title":"Djerroudi et al., E-cadherin inactivation shapes tumor microenvironment specificities  in invasive lobular carcinoma","description":"Invasive lobular breast carcinoma (ILC) shows specific stromal features, T lymphocyte infiltration (TIL) being associated with poor prognosis. Here, we reveal the involved mechanism by performing single cell RNA sequencing, combined immunohistochemistry, deconvolution of bulk RNA sequencing from large retrospective ILC series, and functional assays using primary cells. We show that ILC accumulate FAP+ inflammatory cancer-associated fibroblasts (iCAF) through a previously undescribed mechanism mediated by E-cadherin/CDH1 on CAF plasticity. Indeed, CDH1 inactivation in ILC cancer cells prevents differentiation of iCAF into myofibroblastic CAF (myCAF), leading to iCAF accumulation. In turn, iCAF increase TIL infiltration and shape their spatial organization in ILC. Subsequently, CDH1-inactivated ILC cancer cells promote immune escape by lack of retention and activation of ITGAE-expressing resident memory CD8+ T lymphocytes (TRM). Hence, our study uncovers reciprocal interactions between CDH1-inactivated cancer cells, iCAF and CD8+ TRM, revealing why and how TILs have a poor prognosis in ILC patients, a mechanism extrapolated to other CDH1-mutated cancer types. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-13T09:02:27.141807+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000762","title":"Genotype data from 'The genetic demographic history of the last hunter-gatherer population of the Himalayas: The Raute'","description":"This study presents newly genotyped genome-wide SNP data of the Raute to explore their genetic isolation, their origins and potential as an older foraging lineage, and their genetic connections to other regional foragers. Samples 113 Raute individuals and 44 individuals from surrounding agriculturalist villages in the Dailekh municipality of the Karnali province in Nepal voluntarily were genotyped using the Axiom™ Genome-Wide Human Origins 1 Array, yielding ~600K SNPs. ","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000763","title":"Pediatric B-cell precursor acute lymphoblastic leukemia RNA sequencing","description":"This dataset included 33 childhood B-cell precursor acute lymphoblastic leukemia RNA sequencing samples. All samples were subjected to Illumina pair-end sequencing.\r\n","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-24T17:26:41.11268+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000764","title":"Pediatric B-cell precursor acute lymphoblastic leukemia Micro-C sequencing","description":"This dataset included 35 childhood B-cell precursor (BCP) acute lymphoblastic leukemia Micro-C samples. All samples were subjected to Illumina pair-end sequencing.\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-24T17:26:39.706016+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000765","title":"Germline WES of serrated polyposis syndrome","description":"The serrated polyposis syndrome (SPS) is a disease with a mainly unknown inherited genetic basis characterized by the presence of multiple and/or large serrated polyps in the colon and a higher associated risk for colorectal cancer (CRC). The objective of the present study was to identify new SPS/CRC germline predisposition genes by using whole-exome sequencing in two affected SPS patients from the same family.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[33672345],"external_links":null,"is_released":true,"released_date":"2024-12-23T17:08:15.298908+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000766","title":"Transrenal DNA Analysis","description":"Urinary cell-free DNA (ucfDNA) is an emerging marker in liquid biopsy. However, the characteristics of transrenal DNA and urinary-tract DNA are not fully understood. Therefore, we investigated the fragmentomic features and demonstrated the potential clinical utilities of ucfDNA in the current study.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-03T10:27:32.808042+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000767","title":"A non-canonical lymphoblast in refractory childhood T-cell leukaemia","description":"Refractory cancers may arise either through the acquisition of resistance mechanisms by cancer cells or represent distinct diseases. The origin of childhood T-cell acute lymphoblastic leukaemia (T-ALL) that does not respond to initial treatment, i.e. refractory disease, is unknown. Refractory T-ALL carries a poor prognosis and cannot be predicted at diagnosis. Here, we performed single cell mRNA sequencing of T-ALL from children who did or did not respond to initial treatment. We identified a transcriptionally distinctive blast population, exhibiting features of innate-like lymphocytes, as the major source of refractory disease. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-04T11:56:01.419115+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000768","title":"Integrated Multiomics Uncovers Distinct Macrophage Alterations in Human Metabolic dysfunction-Associated Steatohepatitis Progression","description":"We report single-nuclei RNA sequencing data from human livers in metabolic dysfunction-associated steatotic liver disease (MASLD) patients.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-27T16:31:18.307054+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000769","title":"Human inflammatory cardiomyopathies following SARS-CoV2 infection and COVID-19 vaccination","description":"Title: The cellular and molecular responses in human inflammatory cardiomyopathies following SARS-CoV2 infection and COVID-19 vaccination.\r\nAbstract: Abstract: Myocarditis is a cardiac disorder with multiple etiologies characterised by inflammatory cell infiltration and can occur after SARS-CoV-2 infection or rarely following mRNA-based COVID-19 vaccination. The underlying cellular and molecular mechanisms driving these pathologies remain poorly understood.Here we performed single-nucleus-RNA-sequencing in left ventricular endomyocardial biopsies from patients with Non-COVID-19 myocarditis, following SARS-CoV-2 infection (Post-COVID-19) and COVID-19 vaccination (Post-Vaccination). We detected specific cytokine expression patterns highlighting a particular role of interferon-γ in Post-COVID-19 and upregulated IL16 and IL18 expression as a Post-Vaccination hallmark. While the myeloid response was similar between groups, CD4+T-cell proportions were higher in Post-Vaccination and cytotoxic CD8+T and NK cells expanded in Post-COVID-19. Endothelial cells showed gene expression changes suggestive of vascular barrier function deficiency in Post-COVID-19 and angiogenesis response to cardiac inflammation in all groups. Together, our results illuminate shared and distinct cellular and molecular architectures of Non-COVID-19, Post-COVID-19 and Post-Vaccination associated myocardial inflammation in human hearts. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-31T10:41:02.539705+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000770","title":"Assessment of candidate high-grade serous ovarian carcinoma predisposition genes through integrated germline and tumour sequencing","description":"High-grade serous ovarian carcinoma (HGSOC) has a significant hereditary component, only half of which is explained. Previously, we performed germline exome sequencing on BRCA1 and BRCA2-negative HGSOC patients, revealing three proposed and 43 novel candidate genes enriched with rare loss-of-function variants. For validation, we undertook case-control analyses using genomic data from disease-free controls. This confirms enrichment for nearly all previously identified genes. Additionally, one-hundred-and-eleven HGSOC tumours from variant carriers were sequenced alongside other complementary studies, seeking evidence of biallelic inactivation as supportive evidence. PALB2 and ATM validate as HGSOC predisposition genes, with 6/8 germline carrier tumours exhibiting biallelic inactivation accompanied by characteristic mutational signatures. Among candidate genes, only LLGL2 consistently shows biallelic inactivation and protein expression loss, supporting it as a novel HGSOC susceptibility gene. The remaining candidate genes fail to validate. Integrating case-control analyses with tumour sequencing is thus crucial for accurate gene discovery in familial cancer studies.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-30T14:51:35.435752+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000771","title":"Longitudinal evaluation of circulating tumor DNA in early breast cancer receiving neoadjuvant systemic therapy using a tumor-informed assay","description":"This study evaluates a highly sensitive tumor-informed ctDNA assay in a real-world cohort of patients receiving neoadjuvant therapy (NAT) to assess clinical validity and explores prognostic outcomes","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-27T13:30:13.517458+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000772","title":"Single-cell RNA sequencing of human IL-18R supported CAR T cells targeting oncofetal Tenascin C","description":"C.TNC-CAR.Zip18R CAR-T cells are from 2 donors and multiplexed 10x Genomics scRNA-seq were performed with a hashtag to label each sample. For tumor and CAR-T cell cocluture samples, CAR-T cells were extracted from 3 time points. The raw data are fastq format for total 20 samples considering sequencing lanes. The multiplexing information, CAR and Zip18R sequences are deposited in analyses.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000773","title":"Repression of CADM1 transcription by HPV type 18 is mediated by three-dimensional rearrangement of promoter-enhancer interactions","description":"Repression of CADM1 transcription by HPV type 18 is mediated by three-dimensional rearrangement of promoter-enhancer interactions","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-31T13:59:40.875339+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000774","title":"Whole Exome Sequencing Data of indolent primary renal B-Cell lymphomas","description":"We used sequenced 34 iNHL samples using whole exome sequencing (WES) data to evaluate possible mutational signatures and driver mutations associated with the patient’s clinical and cytogenetic characteristics. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[40353805],"external_links":null,"is_released":true,"released_date":"2025-01-09T09:40:01.83204+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000775","title":"Long-term Survival Update and Extended RAS Mutational Analysis of the CAIRO2 Trial: Addition of Cetuximab to CAPOX/Bevacizumab in Metastatic Colorectal Cancer","description":"Here we present updated survival of the CAIRO2 trial and assessed whether the addition of anti-EGFR to anti-VEGF therapy could still be an effective treatment option for patients with extended RAS/BRAF wildtype and left-sided metastatic colorectal cancer (mCRC).\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-31T13:53:44.511663+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000776","title":"Single-cell RNAseq of hematological toxicity following CAR-T cells injection ","description":"Bone marrow aspirations obtained from patients treated with CAR-T cells were analyzed using single cell RNA sequencing (CD3+, CAR T+, CD34+ sorted populations).","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-22T12:59:17.939256+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000777","title":"Bulk RNA sequencing of hematological toxicity following CAR-T cells injection","description":"Bone marrow aspirations obtained from patients treated with CAR-T cells were analyzed using bulk RNA sequencing (CD3+, CAR T+, CD34+ sorted populations).","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-22T12:59:17.939256+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000778","title":"Analysis of T cells in follicular lymphoma","description":"This study aimed to identify new heterogeneities in human T cells of follicular lymphoma.\r\nTo do so, we performed scRNA-seq of human lymph node and follicular lymphoma samples.\r\nWe identified minor T cell subsets expanding in follicular lymphoma.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-31T13:58:37.103618+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000779","title":"Clinical relevance of TCGA subtypes for gastric cancer patients","description":"There is a clinical need for the availability of molecular biomarkers in the tratment of gastric cancer (GC), since survival rates remain poor with a 5-year survival rate of only ~`40% for patients with resectable disease. These markers will elad to a more tailored approach in the treatment of GC, which enhances efficacy and reduces toxicity. Recently, The Cancer Genome Atlas (TCGA) classified GC patients into four molecular subgroups: Epstein Barr Virus positive (EBV+), genomically stable (GS), microsatellite instable (MSI), and chromosomal instable (CIN). For this purpose we aim to collect tumor tissue blocks from patients who participated in the Dutch D1/D2 or the CRITICS trial and who gave informed consent for translational studies. Associations between TCGA subtypes and outcomes to these different therapeutic options will be analyzed.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2024-12-31T13:53:47.077691+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000780","title":"DAC-2023-07-05-Ritz (DAC-007) - Diagnosis of tuberculosis infection in children with a novel skin test and the traditional tuberculin skin test: an observational study","description":"Diagnosis of tuberculosis infection in children with a novel skin test and the traditional tuberculin skin test: an observational study\r\n\r\nThis is only the location for the raw data and any check if the dataset may be relevant please refer to the MF-DAC Zenodo community (https://zenodo.org/records/11237107).\r\n","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":[{"url": "https://usbch.sharepoint.com/:w:/r/sites/dkf/datarequests/MF-DAC/MF-DAC-requests/DAC-2023-07-05%20Ritz/DAC-007-DAC%20Setup%20Zenodo/00%20MF-DAC_Data%20Request%20Summary%20for%20DAC-2023-07-05%20Ritz.docx?d=w595f14654aa14dce9139982d98642b9a&csf=1&web=1&e=c7UAwu", "name": "EucanImage", "label": "Summary Document"}, {"url": "https://zenodo.org/records/11237107", "name": "PRIDE", "label": "Metadata (Zenodo)"}],"is_released":true,"released_date":"2025-01-16T17:51:15.742063+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000781","title":"The phase II Neo-Pembro trial: neoadjuvant pembrolizumab in stage IV high-grade serous ovarian cancer","description":"While immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, their efficacy in high-grade serous ovarian cancer (HGSOC) remains limited. Nevertheless, some patients achieve lasting responses, emphasizing the need to understand how the tumor microenvironment and molecular characteristics influence ICI response. We hypothesized higher efficacy of ICI when used in the neoadjuvant setting and preceded by induction chemotherapy. The phase 2 Neo-Pembro study (NCT03126812) included 33 untreated patients with stage IV HGSOC who were planned for 6 cycles of carboplatin-paclitaxel and interval cytoreductive surgery. Pembrolizumab (pembro) was added from cycle two and continued for one year. The primary objective was to assess intratumoral immune activation, through multiplexed immunofluorescence and immune-related gene expression. Our data provide evidence of immune activation, characterized by an increase in CD3+, CD8+, CD8+/FOXP3+ ratio, and TNF-α and interferon-γ signaling, and was most evident in major pathologic responders, which were 9/33 patients (27%, 95%CI 14-46) at time of surgery. Pathologic response was strongly associated with overall survival. At a median follow-up of 52.8 months, 8/9 major responders were alive, including 6 patients without recurrence, and 4 of 24 minor responders were alive, including one patient without recurrence. PD-L1 expression and homologous recombination deficiency were predictive of major response and may serve as potential biomarkers, warranting further exploration. In a post-hoc comparison, major responders treated with pembro had significantly better overall survival than major responders in a historic cohort treated without pembro. Our data indicate that immune activation was stronger in the subset of major pathologic responders and these patients may derive long-term survival benefits from the addition of neoadjuvant pembro.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-02-18T18:26:12.476023+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000782","title":"Whole-exome variant calling of individuals from the study of familial pulmonary fibrosis in the Canary Islands","description":"Research study of rare genetic variants associated with familial cases of pulmonary fibrosis in patients and relatives from Canary Islands, Spain.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-27T11:31:48.212452+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000783","title":"Genomic Profiling of an anti-PD-L1 treated cohort of Newly Diagnosed GBM patients","description":"Checkpoint inhibitor therapy has limited efficacy in the outcomes of patients with glioblastoma (GBM). This study involves whole exome sequencing of newly diagnosed glioblastoma patients treated with concurrent atezolizumab, radiation therapy, and temozolomide. By analyzing 29 tumor-normal pairs, the study aims to explore the correlation between tumor genomics and the efficacy of PD-L1 blockade treatment outcomes and further identify which patients may benefit more from such therapy.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-14T13:37:18.336755+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000784","title":"Transcriptomic Profiling of an Anti-PD-L1 Treated Cohort of Newly Diagnosed GBM Patients","description":"Checkpoint inhibitor therapy has limited efficacy in glioblastoma patient outcomes. This study involves RNA sequencing (RNA-seq) of newly diagnosed GBM patients treated with concurrent atezolizumab, radiation therapy, and temozolomide. By analyzing RNA-seq data from 39 tumors, the study aims to explore tumor transcriptomic features, including immune-based transcriptomic programs and immune infiltration, to understand their influence on PD-L1 blockade treatment efficacy and to identify which patients may benefit more from such therapy.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-14T13:37:18.336755+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000785","title":"Tumor-reactive heterotypic CD8 T cell clusters from clinical samples","description":"Emerging evidence suggests a correlation between CD8+ T cell-tumor cell proximity and anti-tumor immune response. However, it remains unknown whether these cells exist as functional clusters that can be isolated from clinical samples. By conventional and imaging flow cytometry, we show here that from 21/21 human melanoma metastases, we could isolate heterotypic clusters, comprising CD8+ T cells interacting with one or more tumor cells and/or antigen-presenting cells (APCs). Single-cell RNA-sequencing revealed that T cells from clusters were enriched for gene signatures associated with tumor reactivity and exhaustion. Clustered T cells exhibited increased TCR clonality indicative of expansion, while TCR-matched T cells showed more exhaustion and co-modulation when conjugated to APCs than to tumor cells. T cells that were expanded from clusters ex vivo exerted on average 9-fold increased killing activity towards autologous melanomas, which was accompanied by enhanced cytokine production. Upon adoptive cell transfer into mice, T cells from clusters showed improved patient-derived melanoma control, which was associated with increased T cell infiltration and activation. Together, these results demonstrate that tumor-reactive CD8+ T cells are enriched in functional clusters with tumor cells and/or APCs and that they can be isolated and expanded from clinical samples. Typically excluded by single cell gating in flow cytometry, these distinct heterotypic T cell clusters serve as a valuable source to decipher functional tumor-immune cell interactions, while they may also be therapeutically explored.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-03T10:31:11.061554+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000786","title":"snRNA:  A Cultured Leukemia Stem Cell Model Enables Validation of CDK6 as a Stemness Target Against Acute Myeloid Leukemia","description":"Acute myeloid leukemia (AML) represents a group of aggressive hematological malignancies, the clinical management of which is made challenging due to the persistence of rare and therapy resistant leukemia stem cells (LSCs) which serve as a source of disease relapse and poor outcomes. There are currently a paucity of methods to reliably enrich and study LSCs, hindering the development of therapies that specifically target LSCs. In this study, we deeply characterize the OCI-AML8227 culture model, which maintains a functional stemness hierarchy originating from its highly primitive CD34⁺CD38⁻ cells, to elucidate LSC biology and uncover LSC-specific therapeutic vulnerabilities. We analyzed both bulk and single-cell proteomics, transcriptomics, and epigenomics to generate a LSC protein-protein interaction network, which was then integrated with an LSC-focused small molecule screen using this model. From these findings, CDK6 was discovered as a therapeutic vulnerability specific to LSCs, which was validated in findings from the BEAT-AML cohort and a patient-derived xenograft (PDX) panel of AML samples through palbociclib treatment. Taken together, our studies validate CDK6 as a druggable vulnerability in LSCs, and authenticate OCI-AML8227 cells as a LSC target discovery engine.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-27T10:49:16.400235+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000787","title":"bulk ATACseq: A Cultured Leukemia Stem Cell Model Enables Validation of CDK6 as a Stemness Target Against Acute Myeloid Leukemia","description":"Acute myeloid leukemia (AML) represents a group of aggressive hematological malignancies, the clinical management of which is made challenging due to the persistence of rare and therapy resistant leukemia stem cells (LSCs) which serve as a source of disease relapse and poor outcomes. There are currently a paucity of methods to reliably enrich and study LSCs, hindering the development of therapies that specifically target LSCs. In this study, we deeply characterize the OCI-AML8227 culture model, which maintains a functional stemness hierarchy originating from its highly primitive CD34⁺CD38⁻ cells, to elucidate LSC biology and uncover LSC-specific therapeutic vulnerabilities. We analyzed both bulk and single-cell proteomics, transcriptomics, and epigenomics to generate a LSC protein-protein interaction network, which was then integrated with an LSC-focused small molecule screen using this model. From these findings, CDK6 was discovered as a therapeutic vulnerability specific to LSCs, which was validated in findings from the BEAT-AML cohort and a patient-derived xenograft (PDX) panel of AML samples through palbociclib treatment. Taken together, our studies validate CDK6 as a druggable vulnerability in LSCs, and authenticate OCI-AML8227 cells as a LSC target discovery engine.\r\n","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-27T10:49:16.400235+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000788","title":"scATAC: A Cultured Leukemia Stem Cell Model Enables Validation of CDK6 as a Stemness Target Against Acute Myeloid Leukemia","description":"Acute myeloid leukemia (AML) represents a group of aggressive hematological malignancies, the clinical management of which is made challenging due to the persistence of rare and therapy resistant leukemia stem cells (LSCs) which serve as a source of disease relapse and poor outcomes. There are currently a paucity of methods to reliably enrich and study LSCs, hindering the development of therapies that specifically target LSCs. In this study, we deeply characterize the OCI-AML8227 culture model, which maintains a functional stemness hierarchy originating from its highly primitive CD34⁺CD38⁻ cells, to elucidate LSC biology and uncover LSC-specific therapeutic vulnerabilities. We analyzed both bulk and single-cell proteomics, transcriptomics, and epigenomics to generate a LSC protein-protein interaction network, which was then integrated with an LSC-focused small molecule screen using this model. From these findings, CDK6 was discovered as a therapeutic vulnerability specific to LSCs, which was validated in findings from the BEAT-AML cohort and a patient-derived xenograft (PDX) panel of AML samples through palbociclib treatment. Taken together, our studies validate CDK6 as a druggable vulnerability in LSCs, and authenticate OCI-AML8227 cells as a LSC target discovery engine.\r\n","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-27T10:49:16.400235+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000789","title":"bulk RNA-seq: A Cultured Leukemia Stem Cell Model Enables Validation of CDK6 as a Stemness Target Against Acute Myeloid Leukemia","description":"Acute myeloid leukemia (AML) represents a group of aggressive hematological malignancies, the clinical management of which is made challenging due to the persistence of rare and therapy resistant leukemia stem cells (LSCs) which serve as a source of disease relapse and poor outcomes. There are currently a paucity of methods to reliably enrich and study LSCs, hindering the development of therapies that specifically target LSCs. In this study, we deeply characterize the OCI-AML8227 culture model, which maintains a functional stemness hierarchy originating from its highly primitive CD34⁺CD38⁻ cells, to elucidate LSC biology and uncover LSC-specific therapeutic vulnerabilities. We analyzed both bulk and single-cell proteomics, transcriptomics, and epigenomics to generate a LSC protein-protein interaction network, which was then integrated with an LSC-focused small molecule screen using this model. From these findings, CDK6 was discovered as a therapeutic vulnerability specific to LSCs, which was validated in findings from the BEAT-AML cohort and a patient-derived xenograft (PDX) panel of AML samples through palbociclib treatment. Taken together, our studies validate CDK6 as a druggable vulnerability in LSCs, and authenticate OCI-AML8227 cells as a LSC target discovery engine.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-27T10:49:16.400235+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000790","title":"A thymic ILC1-like progenitor with differentiation potential towards KIR+NKG2A- NK cells - sc","description":"KIR+NKG2A- Natural Killer (NK) cells have the unique ability to detect downregulation of single HLA-I allotypes, frequently occurring in malignantly-transformed and virus-infected cells in order to escape T cell recognition. We have recently shown that circulating Innate Lymphoid Cells 1 (cILC1) have the potential to generate such KIR+NKG2A- NK cells but their developmental origin was unknown. Here we demonstrate that the development of cILC1 is thymus-dependent and identify a putative progenitor of cILC1s in the thymus, called thyILC1. Single-cell RNAseq analysis revealed a close relationship of thyILC1s to CD34+ double-negative (DN) thymocytes, but in contrast to DNs, thyILC1s had lost T cell differentiation potential. However, like cILC1s they could be efficiently differentiated into KIR+NKG2A- NK cells. thyILC1s strongly expressed RAG1/2, PTCRA (preTCR, and NOTCH1/3, but lacked expression of TCR chains, suggesting that they failed to pass the -selection checkpoint of thymocyte development. Finally, analyses of patients with FOXN1het deficiency, showing thymic hypoplasia due to lack of mature thymic epithelial cells, exhibited a profound deficiency of cILC1s but not cILC2s and cILC3s, demonstrating thymus dependency of cILC1s. Together, the data suggest that thyILC1s are the source of a novel thymus-dependent NK cell differentiation pathway that promotes generation of KIR+NKG2A- NK cells.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-25T10:20:11.860651+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000791","title":"WES in muscle-invasive bladder cancer (MIBC) treated with durvalumab plus olaparib in the neoadjuvant setting: NEODURVARIB trial","description":"This submission contains the metadata derived from the whole exome sequencing of 70 samples from 26 patients who developed advanced urothelial carcinomas. The patients were enrolled in the Neodurvarib clinical trial, which compares the molecular profiles at diagnosis and after neoadjuvant treatment with Durvalumab and Olaparib. In this regard, the analyzed samples include: normal tissue and tumoral tissue obtained from the transurethral resection of the bladder (TURBT, a procedure performed prior to neoadjuvant therapy) from the 26 patients (52 samples), as well as tissue obtained from the radical cystectomy (a procedure performed after treatment with the aforementioned drugs; 18 samples).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-23T09:03:12.515814+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000792","title":"41 fibroblast RNAseq samples of pediatric patients with childhood epilepsy and developmental delay","description":"We used RNA sequencing of patient fibroblasts to find a genetic diagnosis in patients with exome-negative childhood epilepsy. RNA extracted from 41 individuals' cultured fibroblasts (passage 3-6) was collected and sequenced at a depth of 90-110 paired reads per sample.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-27T15:53:45.868797+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000793","title":"Enabling sensitive and precise detection of ctDNA through somatic copy number aberrations in breast cancer","description":"Cell-free DNA (cfDNA) extracted from peripheral blood has emerged as a crucial biomarker source in oncology research. To enhance the detection of somatic copy number alterations (SCNAs) and circulating tumor DNA (ctDNA), we developed eSENSES, a 2Mb breast cancer-targeted NGS panel. It includes 15,000 genome-wide SNPs, 500 focal SNPs in breast cancer driver regions, and exons from 81 commonly altered genes, alongside a custom computational approach. eSENSES provides a reliable, powerful and cost-effective tool for monitoring disease progression and guiding therapeutic decisions in breast cancer patients.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-09T16:21:00.279974+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000794","title":"Subclonal variation in patients with pediatric T-lymphoblastic leukemia (T-ALL)","description":"Variations in TP53 and KRAS genes indicate a particularly poor prognosis in relapsed pediatric T-ALL. We hypothesized that these variations might be subclonally present at disease onset and contribute to relapse risk. To test this, we examined 386 children diagnosed with T-ALL, including more than 100 patients who relapsed as well as matched non-relapsing controls.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-09T12:02:45.125307+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000795","title":"HELIUS paired metagenomics","description":"Shotgun metagenomics samples of 476 subjects at 2 timepoints (baseline and 6-year follow-up) of the HELIUS cohort study. This is a multi-ethnic population-based cohort study in Amsterdam, the Netherlands with in total over 25,000 participants. The 476 participants included for this analysis were of European Dutch or South-Asian Surinamese origin.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-14T13:05:33.609291+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000796","title":"HELIUS 16S follow-up H2","description":"The HELIUS cohort is a longitudinal multi-ethnic population-based cohort study in Amsterdam, the Netherlands. This dataset includes 16S rRNA sequencing data of fecal samples of a subset of about 3000 participants, that attended the 6-year follow-up visit of the HELIUS cohort. These visits took place between 2019 and 2022.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-14T13:05:36.632692+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000797","title":"Young Boost Trial for Breast Cancer patients","description":"The Young Boost Trial (YBT, YOUNG BOOST / BOOG 2004-01 (Borstkanker) | Kanker.nl  investigated the optimal radiation dose for breast cancer patients aged 50 years or younger, treated with breast-conserving therapy (BCT). In this randomized study, participants were assigned to receive either a 26 Gy or a 16 Gy radiation boost, with the primary endpoint being local recurrence. To explore potential predictive biomarkers of treatment response in this patient group, whole exome sequencing (WES) was performed on tumor samples to identify genetic factors that could guide personalized treatment strategies and improve clinical outcomes for these young breast cancer patients.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-07T15:38:02.412895+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000798","title":"EuroTARGET is a European study on mRCC, collecting clinical data, germline DNA, and tumor samples.","description":"For patients with metastatic renal cell cancer (mRCC), treatment choice is mainly based on clinical parameters. With many treatments available and the limited response to treatment and associated toxicities, there is much interest in identifying better biomarkers for personalized treatment. EuroTARGET aims to identify and characterize host- and tumor-related biomarkers for prediction of response to tyrosine kinase inhibitor therapy in mRCC. Here, we describe the EuroTARGET mRCC patient cohort.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[28385611],"external_links":null,"is_released":true,"released_date":"2025-01-29T18:26:01.636304+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000799","title":"Ultrasensitive Detection and Monitoring of Circulating Tumor DNA using Structural Variants in Early-Stage Breast Cancer","description":"Circulating tumor DNA (ctDNA) detection has an emerging role in the management of breast \r\ncancer, offering a non-invasive means to monitor disease status and detect recurrence. This study demonstrates that longitudinal monitoring of tumor-specific structural variants - frequent alterations observed across many tumor types including all subtypes of breast cancer derived from Whole Genome Sequencing data - allows for ctDNA detection in nearly all participants in this cohort with untreated early breast cancer prior to starting neoadjuvant therapy. On-treatment ctDNA monitoring enabled the early identification of patients at high risk of recurrence and ctDNA was detected prior to relapse in participants across all receptor subtypes. These findings demonstrate the clinical validity of this assay approach for ultrasensitive ctDNA monitoring.\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-04T08:25:54.897092+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000800","title":"Genomic analysis of head and neck squamous cell carcinoma upon acquired resistance to cetuximab","description":"Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab) remain the only FDA-approved targeted therapy for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Unfortunately, most patients develop acquired resistance to cetuximab and there is currently no further therapeutic option for these patients (unmet clinical need), thereby highlighting the need to better understand resistance-causing mechanisms. Here, we carried out whole-exome sequencing on 2 cetuximab-sensitive and -resistant patient-derived xenograft models of HNSCC. Our data reveal several genetic alterations (mutations and copy number variations) associated with acquired resistance to anti-EGFR therapy.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-23T16:49:53.209081+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000801","title":"Single-cell Analysis of Neoplastic Plasma Cells Identifies Novel Myeloma Pathobiology Mediators and Potential Targets","description":"Newly diagnosed symptomatic and relapsed/refractory myeloma is a clonal plasma cell (PC) dyscrasia that arises from precursors which have been studied utilizing bulk or single-cell (sc) techniques. By combining scRNA-sequencing with scB-cell receptor (BCR)-sequencing, we found more dysregulated genes in monoclonal PCs compared with analyses of the entire CD138+ population, which includes non-neoplastic/polyclonal PCs. Paired tumor and non-tumor WGS was performed to evaluate the presence of IgH-associated translocations and hyperdiploidy events, initially detected by FISH, in a subset of samples included in this study. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-28T14:09:30.536111+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000802","title":"Single-cell Analysis of Neoplastic Plasma Cells Identifies Myeloma Pathobiology Mediators and Potential Targets","description":"Multiple myeloma is a clonal plasma cell (PC) dyscrasia that arises from precursors and has been studied utilizing approaches focused on CD138+ cells.  By combining single-cell (sc)RNA- with scB-cell receptor (BCR)-sequencing, we differentiate monoclonal/neoplastic from polyclonal/normal PCs, and find more dysregulated genes, especially in precursor patients, than by analyzing bulk PCs.  To determine if this approach can identify oncogenes that contribute to disease pathobiology, MAD2L1 and MAT2A are validated as targets with drug-like molecules that suppress myeloma growth in pre-clinical models.  Moreover, functional studies show a role of LAMP5, which is uniquely expressed in neoplastic PCs, in tumor progression and aggressiveness via interactions with c-MYC.  Finally, a monoclonal antibody recognizing cell-surface LAMP5 shows efficacy as an antibody-drug conjugate and in a chimeric antigen receptor-guided T-cell format. These studies provide additional insights into myeloma biology and identify potential targeted therapeutic approaches that can be applied to reverse myeloma progression.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-28T14:09:34.554483+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000803","title":"Single-cell Analysis of Neoplastic Plasma Cells Identifies Novel Myeloma Pathobiology Mediators and Potential Targets","description":"Newly diagnosed symptomatic and relapsed/refractory myeloma is a clonal plasma cell (PC) dyscrasia that arises from precursors which have been studied utilizing bulk or single-cell (sc) techniques. By combining scRNA-sequencing with scB-cell receptor (BCR)-sequencing, we found more dysregulated genes in monoclonal PCs compared with analyses of the entire CD138+ population, which includes non-neoplastic/polyclonal PCs. We identified a panel of genes that were over- or under-expressed in symptomatic states that could be putative oncogenic drivers or tumor suppressors, respectively. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-01-28T14:09:37.142728+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000804","title":"Clinical validity of post-surgery circulating tumor DNA (ctDNA) in stage III colon cancer patients treated with adjuvant chemotherapy: the PROVENC3 study","description":"The PROVENC3 study aimed to determine the clinical validity of post-surgery ctDNA testing in patients with stage III colon cancer treated with adjuvant chemotherapy (ACT). Blood was collected pre-surgery, post-surgery and post-adjuvant chemotherapy. Tumor-informed plasma ctDNA detection was performed through integrated whole genome sequencing (WGS) analyses of formalin-fixed paraffin-embedded tumor tissue DNA (80x), white blood cell germline DNA (40x) and plasma cell-free DNA (30x). These raw WGS data for 209 patients are shared in .cram format in this EGA submission. For 196/209 of these patients there is overlapping FFPE tumor RNA sequencing data available, shared in .fastq format in this EGA submission.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[41650786,41511870],"external_links":null,"is_released":true,"released_date":"2025-05-02T00:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000805","title":"RODAM cohort","description":"The RODAM study assesses the health and wellbeing of Ghanaian residents in Ghana and Europe and follows them up over time. With this unique approach the RODAM study attempts to unravel the causes of cardiovascular disease and its risk factors among African migrants in Europe and non-migrants sub-Saharan Africa. Fecal samples from RODAM participants in rural, urban Ghana and Amsterdam, the Netherlands were sequenced using 16S rRNA sequencing to assess gut microbiome differences between research sites.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-04T10:03:41.451901+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000806","title":"MethylBERT enables read-level DNA methylation pattern identification and tumour deconvolution using a Transformer-based model","description":"DNA methylation (DNAm) is a key epigenetic mark that shows profound alterations in cancer. Read-level methylomes enable more in-depth DNAm analysis due to the broad coverage and preservation of rare cell-type signals, compared to array-based data such as 450K/EPIC array. Here, we propose MethylBERT, a novel Transformer-based model for read-level methylation pattern classification. MethylBERT identifies tumour-derived sequence reads based on their methylation patterns and genomic sequence and the method estimates tumour cell fractions within bulk samples. In our evaluation, MethylBERT outperforms existing deconvolution methods and demonstrates high accuracy regardless of methylation pattern complexity, read length and read coverage. Moreover, we show its applicability to cell-type deconvolution as well as non-invasive early cancer diagnostics using liquid biopsy samples. MethylBERT represents a significant advancement in read-level methylome analysis and enables accurate tumour purity estimation. The broad applicability of MethylBERT will enhance studies on both tumour and non-cancerous bulk methylomes.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-12T11:41:15.161209+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000807","title":"ECM-free patient-derived organoids preserve diverse prostate cancer lineages and uncover in vitro-enriched cell types","description":"Patient-derived organoids (PDOs) hold promise for modeling various cancers, yet their application in prostate cancer (PCa) has been limited due to low culture success and the predominance of non-tumor-like cells. Using 164 PCa samples and optimizing culture conditions, we demonstrate that an extracellular matrix (ECM)-free culture method improves PDO take-rates, fostering cell populations with luminal and PCa-specific characteristics. Single-cell RNA sequencing (scRNA-seq) reveals that these ECM-free PDOs closely mirror their original tumors at the transcriptomic level and maintain a diverse array of tumor cell types, unlike traditional Matrigel-based cultures which predominantly yield benign-like cells. This study introduces a PCa PDO single-cell atlas, providing a valuable resource for advancing prostate cancer research.\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-02T09:54:49.627429+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000808","title":"Impact of Glycolysis Inhibition on the Epigenome of Synovial Fluid T Cells in Juvenile Idiopathic Arthritis","description":"Juvenile Idiopathic Arthritis (JIA) encompasses a group of childhood-onset autoimmune conditions characterized by joint inflammation and mononuclear cell infiltration, especially of activated CD4+ memory/effector T (Tmem/Teff) cells in synovial fluid (SF). JIA CD4+ T cells exhibit a distinct inflammation-associated epigenomic profile, though the underlying molecular mechanisms remain unclear.\r\n\r\nThis study investigates the role of glycolysis in shaping the epigenomic landscape of JIA SF CD4+ T cells, with a focus on H3K27ac histone modifications. Using an ex vivo model of antigen stimulation, CD4+ T cells were isolated from peripheral blood (PB) of healthy controls (HC) and synovial fluid from JIA patients. Cells were activated in vitro with anti-CD3/CD28 for 24 hours, and changes in H3K27ac were assessed by chromatin immunoprecipitation followed by sequencing (ChIP-seq).\r\n\r\nTo explore the specific role of glycolysis, cells were also treated with 2-deoxyglucose (2DG), an inhibitor of glucose-6-phosphate production. This inhibition impacted both H3K27ac acetylation patterns and gene expression associated with the activated epigenomic regions.\r\n\r\nAdditionally, HC CD4+ T cells were activated in vitro in the presence of 30% SF or 30% plasma from JIA patients. RNA sequencing (RNA-seq) was performed to examine SF-induced transcriptional changes, providing insight into the metabolic dysregulation and epigenomic alterations observed in JIA SF CD4+ T cells.\r\n\r\nThis dataset includes ChIP-seq and RNA-seq data that collectively advance our understanding of how glycolysis and the SF environment contribute to the epigenetic and transcriptional regulation in JIA CD4+ T cells.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-10T09:49:45.627131+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000809","title":"Integrative analysis reveals a macrophage-predominant, immunosuppressive immune microenvironment and subtype-specific therapeutic vulnerabilities in advanced salivary gland cancer","description":"Background Salivary gland cancers (SGC) are rare and heterogeneous malignant tumors. Advanced SGC lack established treatment options and show poor response to immunotherapy. Here, an integrative multi-omics analysis in a large cohort of advanced SGC revealed insights into the tumor immune microenvironment (TIM) and distinct mechanisms of immune evasion.\r\n\r\nMethods A total of 104 patients with recurrent/metastatic SGC from the DKTK MASTER program were included in this study. Whole-exome or whole-genome sequencing and RNA-sequencing was performed on fresh frozen tumor tissue. The tumor immune microenvironment was analyzed using CIBERSORT deconvolution analysis and immune gene expression scores in bulk RNA-sequencing data. Single-nuclei sequencing and immunohistochemistry analyses were performed in selected samples. Results were validated in bulk RNA-sequencing data of a previously published independent dataset.\r\n\r\nResults Bulk transcriptome analysis revealed an immune-deserted TIM in the majority of advanced SGC samples. Immune exclusion was most prominent in adenoid cystic carcinoma (ACC) subgroup 1 exhibiting a downregulation of the antigen processing machinery. Only a small subset of advanced SGC, including few adenoid cystic carcinoma, exhibited T-cell inflammation, which was correlated with tumor mutational burden in Non-ACC samples. Subtype specific expression of immune checkpoints as well as cancer testis antigens were identified with prominent expression of VTCN1 in luminal cells within ACC. Single-cell RNA-sequencing and bulk RNA-seq deconvolution analysis validated immune cell exclusion and revealed a TIM that was dominated by M2 macrophages across SGC subtypes. Among evaluable patients treated with immune checkpoint inhibitors, a high T-cell to macrophage ratio was associated with clinical benefit.\r\n\r\nConclusions These data support biomarker-based development of immune-checkpoint inhibition and the development of novel immune-checkpoint inhibitors and cellular therapies in SGC.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-03T09:56:48.041829+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000810","title":"Integrated Transcriptomic and Regulatory RNA Profiling Reflects Complex Pathophysiology and Uncovers a Conserved Gene Signature in End Stage Heart Failure RNA-Seq data","description":"Heart failure (HF) is a complex syndrome. Despite availability of multiple treatment options, the mortality remains high and the quality of life poor. Better understanding of the underlying pathophysiological processes can lead to development of novel therapies. Multiple comparative transcriptomics studies, which revealed gene level changes in the key pathophysiological pathways in failing hearts, point towards heterogeneity from interplay of disease stage, etiologies and ethnicity. Transcriptomic characterization of HF in patients from different ethnicities can potentially help in understanding the heterogeneity imparted by various factors and the core elements in heart failure.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-11T13:19:19.078063+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000811","title":"Measles oncolytic virus as an immunotherapy for recurrent/refractory pediatric medulloblastoma and atypical teratoid rhabdoid tumor","description":"Pediatric recurrent medulloblastoma (MB) and atypical teratoid rhabdoid tumor (ATRT) are largely incurable and warrant novel therapies. We investigated a) the safety of a measles virus variant, MV-NIS, in a pediatric phase 1 study and b) the mechanisms of MV-NIS and potential benefit of combination with immune checkpoint inhibition (ICI). Pediatric patients with recurrent MB or ATRT were treated with intratumoral injections for local recurrence or via lumbar puncture for disseminated recurrence. We evaluated local immune responses to MV-NIS with and without ICI via single-cell and bulk RNA sequencing in an intracranial, immunocompetent, syngeneic murine model. MV-NIS given intratumorally or via repeat intrathecal dosing was safe. MV-NIS prolonged survival in murine models but did not demonstrate additive benefit with ICI. No changes in tumor-infiltrating immune-cell composition or activation were observed in response to MV-NIS treatment; however, MV-NIS induced local expression of neutralizing antibodies, complement cascade, and phagocytosis-related genes.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-15T11:20:30.2774+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000812","title":"Whole Exome Sequencing of a Lung Adenocarcinoma Patient Across Three Time Points","description":"A 65-year-old female patient with a significant smoking history (40 pack-years) was first diagnosed with lung adenocarcinoma (LUAD) in the left lung in May 2020 (L1-T1). One year later, in May 2021, the patient progressed with a new LUAD in the right lung (L1-T2) and in May 2024, another LUAD emerged in the right lung (L1-T3).  Whole Exome Sequencing (WES) analysis was conducted on three tumor biopsies obtained at different time points from the same patient to investigate clonal trajectories.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-06T16:02:04.338176+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000813","title":"Spatial heterogeneity, stromal phenotypes, and therapeutic vulnerabilities in colorectal cancer peritoneal metastasis","description":"Peritoneal metastases (PM) in colorectal cancer (CRC) portend a poor prognosis. We sought to elucidate molecular features differentiating primary tumors (PTs) from PMs and actionable targets facilitating transcoelomic dissemination and progression. We performed multi-omic profiling of 217 samples from 136 patients, including 56 primary tumor (PT) and 120 PMs comprising 25 matched PT-PM pairs. Whole exome, and bulk RNA-seq analysis was conducted to identify underlying genomic aberrations and transcriptomic differences between primary and peritoneal lesions. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-17T16:42:38.27555+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000814","title":"RNASeq from PPGL-derived PC12 cell lines cultivated in normoxia and hypoxia conditions. ","description":"PC12 cells derived from rat PPGL were then either continued cultivated in the same normoxia condition (37˚C, 5% CO2 and 21% O2 balanced with N2) or were placed in a hypoxic incubator, that maintained a constant hypoxic environment (37˚C, 5% CO2 and 1% O2 balanced with N2), for different short (12h, 24h, and 48h) or prolonged time (36 days, approximately 860h).","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-07T16:27:47.174598+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000815","title":"WES of paired gDNAs and PPGL tumor DNA from patients with CCHD-PPGL.","description":"WES of paired germline DNA (12) and PPGL tumor DNA (14) from peripheral blood/saliva and formalin-fixed paraffin-embedded (FFPE) blocks from surgery, respectively, from patients with congenital heart disease (CCHD) and pheochromocytoma and paraganglioma (PPGL). ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-07T16:27:48.437236+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000816","title":"Single-cell multi-omics identifies VEGFA-mediated angiogenesis as a driver of relapse in Sonic Hedgehog Medulloblastoma","description":"Relapse in Sonic Hegdehog Medulloblastoma (SHH-MB) a common pediatric brain tumor, remain a significant clinical challenge due to its poor prognosis and limited therapeutic intervention. Understanding the underlying molecular mechanisms driving relapse is critical for developing targeted interventions. Here, we utilize single-cell multi-omics, combining single-nucleus RNA sequencing (snRNA-seq), single-nucleus ATAC sequencing (snATAC-seq), and spatial omics to comprehensively characterize the cellular landscape and regulatory networks associated with SHH medulloblastoma relapse. Our integrative analysis identifies distinct GCP population enriched with angiogenic activity characterized high expression of Vascular Endothelial Growth Factor A (VEGFA) regulated by the transcription factor HIF1A. Notably, we find that VEGFA-mediated angiogenesis is a critical driver of tumor recurrence, promoting a microenvironment that supports tumor revascularization and growth in the endothelial cells. Furthermore, we uncover potential therapeutic targets within the VEGFA signaling axis that could disrupt angiogenesis and reduce relapse rates. Our findings provide new insights into the molecular and cellular dynamics of SHH medulloblastoma relapse and highlight VEGFA as a key mediator of angiogenesis-driven recurrence, offering a promising avenue for therapeutic intervention.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000817","title":"Gene expression adaptation of metastases to their host tissue","description":"The adaptation of metastatic cells to their host tissue critically determines the pathogenicity of a cancer and therefore patient survival. Yet, it remains elusive to what extent the host environment drives gene expression programs in metastatic cells. Here we identify adaptive mechanisms that enable metastases to establish themselves in a novel tissue context. We performed single-cell RNA-sequencing on malignant and benign tissue samples from untreated donors with colorectal adenocarcinoma and liver metastasis to deduce tissue adaptive expression patterns. A novel computational approach identified genes and pathways that consistently adapted to the host tissue at the transition from the primary tumor to the paired metastasis across donors. This analysis revealed that the majority of expression changes in the metastasis reflect an expression signature reminiscent of benign liver epithelial cells. Cellular processes adapting to the liver environment include basic cellular functions such as energy metabolism, as well as tissue-specific pathways such as the regulation of lipid metabolism by PPAR-α. These adaptations potentially increase the pathogenicity of the metastatic cells and may provide new therapeutic strategies.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-31T15:25:30.144609+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000818","title":"Primary T-cell differentiation to T helper subtypes","description":"human CD4+ T cells differentiated to diverse T helper subtypes","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-16T15:35:48.332859+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000819","title":"CRISPRi/a of GATA2/NR4A2/SOX17 upon spontaneous iPSC differentiation","description":"Arrayed CRISPR screens, modulating the expression of key lineage TFs GATA2 (mesoderm), SOX17 (endoderm), and NR4A2 (neuroectoderm) in hiPSCs via CRISPR interference or activation over a time-course of  spontaneous differentiation (days cultured in vitro: 0, 4, 12, and 18).","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-16T15:35:51.238005+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000820","title":"Macrophage polarisation to M1 and M2 phenotypes","description":"iPSC-derived macrophages were polarised with LPS/IFN-gamma or IL4 to M1 and M2 phenotypes, respectively. ","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-16T15:35:53.475174+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000821","title":"Genetic lineage tracing reveals a transient mechanism of telomere repair in group 3 medulloblastoma that can be targeted for therapeutic benefit","description":"Stalled differentiation of rhombic-lip (RL) progenitors is the source of group 3 (G3) medulloblastomas (MBs). However, the mechanism of telomere repair in G3 MB is unknown. We profiled N=36 human MBs via single-nucleus RNA and epigenetic assays and compared those data to genetic lineage-tracing in MB xenografts. MB cells exhibit plasticity and frequent de-differentiation. Embryonal gene zinc-finger and SCAN-domain containing-4 (ZSCAN4) activates an enhancer network in RL progenitor-like cells that drives telomere repair. ZSCAN4 inhibition led to significant telomere shortening, telomeric DNA damage, telomere fusions, decreased proliferation, and significantly increased the survival of orthotopic xenografts. Conversely, ZSCAN4 over-expression induced significant telomere elongation, increased proliferation, and reduced xenograft survival. ZSCAN4, telomere maintenance, and xenograft viability could be targeted by repurposing FDA-approved brain-penetrant drugs with no toxicities. Our data indicate an embryonal mechanism of telomere repair is utilized by embryonal brain tumors such as MB and can be targeted for therapeutic benefit.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000822","title":"Genome-wide evaluation of the maturation of the immune response to the tuberculin skin test from day 2 to day 7","description":"The tuberculin skin test (TST) is a standardised human challenge model to evaluate the immune response to Mycobacterium tuberculosis (Mtb) antigens in vivo. To study the temporal evolution of the TST, we recruited healthy volunteers with evidence of peripheral blood Mtb reactive T cells, to undergo a TST in each arm that was sampled on day 2 at one site and on day 7 at the contralateral site on day 7. Genome-wide TST transcriptomes at day 2 and day 7 were defined by differential gene expression compared to transcriptomes from the site of control saline injections performed in a separate subset of volunteers.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-24T12:20:48.946301+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000823","title":"Next-generation molecular analysis of surgical margins in oral squamous cell carcinoma for assessment of microscopic residual disease and personalized postoperative treatment decision","description":"Background : Patients operated for an early oral squamous cell carcinoma (OSCC) with clear margins have a 5-year local relapse rate of around 15%. Assessing the microscopic residual disease (MRD) remains a challenge.\r\nIn a phase II prospective trial, we evaluated the tetranucleotide microsatellite instability markers in the surgical margins in T1-T2 OSCC resected with pathologically clear margins.\r\n\r\nGoal : Detect MRD in surgical margins and adapt the postoperative decision-making\r\n\r\nDetails : Whole exome sequencing (WES) on early oral squamous cell carcinoma (OSCC) with clear margins, and on resection margins, 86 patients with a median follow-up of 58 months (range 30.4-83 months)\r\n","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-11T15:49:20.559609+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000824","title":"Transcriptomic profiling of granulosa cells from IVF patients at different ages","description":"Two major factors contributing to reduced fertility is use of exogenous hormones and old age. Here, we sequenced RNA from granulosa cell samples from human patients undergoing in vitro fertilization to test how hormonally stimulated cells' transcriptional profiles change with age. All patients were normal responders referred for male infertility and were grouped into two age groups. The gene expression differences in aging were compared to mouse data (previous experiments, see ArrayExpress E-MTAB-13479) and the results are published in the article \"Granulosa cell transcription is similarly impacted by superovulation and aging and predicts early embryonic trajectories\". Corresponding count tables are available in ArrayExpress (E-MTAB-13496).","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-11T11:45:43.363851+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000825","title":"Single Cell RNA Transcriptomics of Mantle Cell Lymphoma Reveals the Presence of Treatment-Resistant Subclones at the Time of Diagnosis","description":"Mantle cell lymphoma is a chronically relapsing B cell neoplasm characterized by clonal heterogeneity. We implemented single cell RNA sequencing of paired tumor samples from four patients with an aggressive nodal MCL at diagnosis and after failure of standard immunochemotherapy. Clustering the cells based on the inferred CNVs showed small subclones present at diagnosis with a CNV profile similar to the major subclone at relapse. Comparison of these subclones to major subclones present at diagnosis revealed 119 upregulated pathways common for the four patient with an aggressive MCL, including NF-kappaB and PTEN signaling pathways. Additionally, we sequenced a patient with an indolent to blastoid MCL transformation with intestinal tissue involvement. In contrast to other compartments at relapse, the cells in the intestine showed strikingly different CNV profile and presence of new driver mutations including NOTCH1. In conclusion, our study demonstrates that scRNAseq can potentially detect therapy resistant subclones at diagnosis.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-19T12:29:32.998777+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000826","title":" Tumor-resident T-cell regulate responses to checkpoint blockade immunotherapies","description":"In cancer models, CD103+CD8 TRM cells are implicated in the response to anti-PD-1 immunotherapy, and a subset of CD4 TRM cells expressing the integrin CD49a is required for response to anti-CTLA-4 immunotherapy. We performed single-cell RNA sequencing on tumour-infiltrating T lymphocytes (TILs) isolated from colon carcinoma et unsupervised analyses reveal several TRM populations. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-26T10:37:02.195117+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000827","title":"TNFα and Immune Cell Activation are associated with Responses to Bemcentinib and Low-Dose Cytarabine in AML Patients","description":"CITEseq/scRNAseq data from longitudinally sampled bone marrow mononuclear cells from acute myeloid leukemia patients treated with bemcentinib plus low dose cytarabine participating in the NCT02488408 clinical trial.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000828","title":"Vascularized human retinal organoids","description":"Single cell RNA sequencing of human retinal organoids that have been vascularized. Assesses the impact of vascularization on cell types and their gene expression.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-27T17:11:00.089161+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000829","title":"Identification of phenotype-modifier genes","description":"Patients were stratified at the extremes of the renal phenotype according to their estimated glomerular filtration rate annual decline and subjected to whole exome sequencing (WES) aiming to find candidate phenotype-modifier genes. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-12T11:29:44.71911+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000830","title":"Single-cell Transcriptome Profiling of Treatment-naïve and Post-treatment Colorectal Cancer: Insights into Putative Mechanisms of Chemoresistance","description":"Drug resistance remains a major clinical challenge in the treatment of colorectal cancer (CRC) with conventional chemotherapy. Investigation of cancer cells and tumor microenvironment (TME) following chemotherapy is critical for unraveling the mechanisms of resistance. In this study, we analyzed scRNA-Seq data from 56 CRCs including treatment-naïve tumors (25 microsatellite stable (MSS) tumors and 7 tumors with microsatellite instability (MSI)); and tumors treated with standard chemotherapy with the known response status (18 responders and 6 progressors). We observed in treatment-naïve MSS CRC that right-sided tumors are more immunogenic with higher numbers of B cells and CD8+ T memory effector cells than left-sided tumors. MSI CRC were even more immunogenic then MSS CRC and were characterized by elevated Tregs in their TME. In the post-treatment CRC there was a high prevalence of dendritic cells (DC) in the TME in the response group. The DC-derived signature was associated with better survival in a large CRC cohort from the TCGA. We also observed two fibroblast subtypes in CRC, one of which was enriched in progressors and was associated with poor survival in a CRC-TCGA cohort. Progressors also showed elevated exhausted CD8+ T memory cells and monocytes suggesting a pro-inflammatory TME. In tumor cells in progressor group we identified specific expression of chemo-protective markers MTRNR2L1 and CDX1; and their co-expression with stemness-related marker CD24. In summary, scRNA-Seq provides a valuable information for the discovery of prognostic markers, and reveals distinct features of CRC based on location, metastasis status, MSI status and treatment response status. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-01T12:12:56.705043+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000831","title":"Constrained hypermutation and absence of TERT promoter mutations in Lynch syndrome-associated urothelial cancer","description":"Lynch syndrome is a hereditary condition characterized by defective DNA mismatch repair and high incidence of several cancers, including urothelial cancers (UC) of the upper urinary tract and bladder. We set out to study the somatic landscape of LS-associated urothelial cancer (LS-UC) by analyzing 41 surgical tumor samples and 3 urine DNA samples from 34 LS-UC patients.","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-19T14:51:37.713806+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000832","title":"Transcriptomics profiling of paired pre- and post- neo-adjuvant endocrine therapy of ERa positive breast cancers","description":"Patients were treated with aromatase inhibitors for up to three months before surgical removal of the primary tumor. Sampling was performed at diagnosis and at surgery, and RNA-seq was performed.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-28T09:42:18.89069+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000833","title":"Prime-seq of human term placenta-derived trophoblast organoids","description":"To study the one of the mechanisms through which obesity could affect placental cells, we used a novel microfluidic organs-on-a-chip device fabricated for co-culturing adipose spheroids and trophoblast organoids. The organoids were derived from the term placenta of a over-weight women. The adipose spheorids were derived from the white adipose tissue of a woman. And we sequenced the RNAs from the trophoblast organoids. The RNA extracted were subjective to Prime-seq library preparation protocol and being sequenced on Illumina NovaSeq 6000 at Novogene. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-19T12:20:16.311249+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000834","title":"comparing the snRNA-seq from placentas of mothers with or without obesity ","description":"Obesity poses risks to maternal health and increases the likelihood of short- and long-term adverse pregnancy outcomes in the offspring. The placenta, a key organ at the maternal-fetal interface, responds to maternal obesity and regulates fetal growth. To investigate the molecular features of physiological adaptation, we perform single-nuclei RNA-seq on human placentas and compared the transcriptomic profiles of women with obesity delivering appropriate- or large-for-gestational age (i.e., AGA and LGA) babies with those from normal-weight healthy controls with AGA babies. The snRNA-seq libraries were generated with Chromium Single Cell 3’ kit v3.1 (10X Genomics) and sequenced on Illumina NovaSeq 6000 at Novogene.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-07T11:47:26.523575+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000835","title":"Analyses of transcriptome and epigenome in cardiac fibroblasts","description":"We report genome-wide bulk RNA- and ATAC-seq analysis of cardiac fibroblasts isolated from two patients. Cells were pre-treated with either KAT5 inhibitor or vehicle, and their fibrotic responses after TGF-β stimulation was measured.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-16T11:11:39.543604+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000836","title":"metastatic uveal melanoma tumour biopsies (n=35)","description":"Tumour biopsies were obtained from uveal melanoma patients (n = 35) pre and 16 days post treatment with tebentafusp. Biopsies, which were either snap frozen or put in RNA later, were analysed by bulk RNA sequencing (50 million reads per sample) using the Illumina NovaSeq system.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-11T15:47:30.103831+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000837","title":"Sequencing of  in vitro generated macrophages and T cells","description":"Monocyte derived macrophages were polarised into M1 or M2 using IFNg+ ILP or IL-4 respectively (n =4) . Pan T cells were cultured with or without IL-2 for 4 days (n=4 - 6). Pan T cells were co-cultured with THP1 tumour cells for 20 hours in the presence or absence of ImmTAC molecules and in the presence or absence of M2 macrophages. Sorted T cells and macrophage populations prior and post co-culture were analysed by bulk RNA sequencing (60 million reads per sample) using the Illumina NovaSeq system.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-11T15:47:50.55402+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000838","title":"Single-cell RNA seq-derived signatures define response patterns to atezolizumab + bevacizumab in advanced hepatocellular carcinoma","description":"FASTq files and normalised gene expression counts from bulk RNA-sequencing of pre-treatment tumour (n=39) and adjacent non-tumour tissue samples (n=13) from advanced hepatocellular carcinoma (HCC) patients treated with atezolizumab plus bevacizumab.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-13T16:16:13.79781+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000839","title":" Mosunetuzumab in Elderly or Unfit Patients with Previously Untreated DLBCL","description":"Background: Tolerability of first-line therapies for diffuse large B-cell lymphoma (DLBCL) in elderly/unfit patients remains a challenge due to toxicities. This study evaluates the efficacy/safety of mosunetuzumab, a CD20xCD3 T-cell-engaging bispecific antibody, which shows promise in this population where chemotherapy is challenging.\r\nMethods: In this phase 1/2 study, we administered fixed-duration intravenous mosunetuzumab monotherapy to elderly (≥80 years) or unfit (60–79 years, unfit for full-dose chemotherapy) patients with untreated DLBCL. The primary endpoint was investigator-assessed overall response rate (ORR) at primary response assessment at the end of treatment (EOT) by positron emission tomography-computed tomography. \r\nResults: Among the 54 patients who received mosunetuzumab, the ORR and complete response (CR) rate at the EOT were 44% (95% CI, 31 to 59) and 35% (95% CI, 23 to 49), respectively. After a median follow-up of 37.6 months, median duration of CR was 35.0 months (95% CI, 9.7 to not estimable [NE]). Median progression-free survival (PFS) was 6.6 months (95% CI, 3.0 to 12.1; 24-month PFS was 25%); median overall survival was 37.7 months (95% CI, 14.1 to NE). The most common adverse events (AEs) were rash/maculopapular rash (31%) and cytokine release syndrome (26%; none grade ≥3). The most common grade ≥3 AE was neutropenia (13%; febrile neutropenia [n=1]). Responders exhibited higher levels of granzyme B-positive cells and CD8-positive T cells in baseline tumor biopsies versus non-responders.\r\nConclusions: First-line mosunetuzumab monotherapy was effective with a manageable safety profile in elderly/unfit patients with DLBCL (Funded by F. Hoffmann-La Roche Ltd; ClinicalTrials.gov number, NCT03677154).","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000840","title":"Clonal Evolution of PPM1D Mutations in the Spectrum of Myeloid Disorders","description":"PPM1D, a central regulator of the DNA damage response, is commonly mutated in therapy-related clonal hematopoiesis (CH), acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). PPM1D mutations have been shown to expand under selective pressure of DNA-damaging chemotherapy. However, whether PPM1D mutations promote the development of hematologic malignancies remains unclear. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-25T12:27:11.498527+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000841","title":"DLGG sequencing","description":"NGS panel based sequencing of disseminated pediatric low-grade glioma (DLGG). This is a dataset from the international DLGG consortium of patients from 0-44 years of age at diagnosis, and diagnosed between 1988-2024. Sequencing was done at the Hospital for Sick Children (Toronto, Canada). The goal of this study was to define the genetic drivers in DLGG and compare them to non-disseminated pediatric low-grade gliomas.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000842","title":"Detection of causative structural variants using long read whole genome sequencing in patients with non-syndromic autism spectrum disorder","description":"This study involved performing long read whole genome sequencing using Oxford Nanopore Technology platform on to detect causative structural variants in patients with non-syndromic autism spectrum disorder. This study was performed on 23 such children in whom prior karyotyping, Fragile-X analysis (in males), chromosomal microarray and whole exome sequencing did not identify a causative variant.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-07T16:33:23.048208+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000843","title":"Immune Landscape of Cervical Lymph Nodes in Multiple Sclerosis ","description":"This study aimed to investigate the cellular compartment of deep cervical lymph nodes (dcLNs) during early MS before the influence of immunosuppressive treatments. We used ultrasound-guided FNAs followed by scRNA-seq,CITE-seq, TCR and BCR seq to characterize the immune landscape in MS patients compared to controls within the dcLNs. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-12T11:36:03.191327+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000844","title":"Error-corrected flow-based sequencing at whole genome scale and its application to circulating cell-free DNA profiling","description":"Differentiating sequencing errors from true variants is a central genomics challenge calling for error suppression strategies that balance costs when sparse material or ultra-rare variants require high-accuracy methods. For example, circulating cell-free DNA (ccfDNA) sequencing for cancer monitoring is limited by sparsity of circulating tumor DNA (ctDNA), abundance of genomic material in samples, library preparation error rates  and sequencing errors. Whole-genome sequencing (WGS) can overcome the low abundance of ccfDNA by integrating signal across the mutation landscape, but higher cost limits  adoption compared with targeted panels, where ccfDNA abundance limits maximal coverage depths. Here we applied deep (~120x) lower-cost WGS (Ultima Genomics) with analytic error correction for tumor-informed ctDNA detection within the part-per-million range. We further developed high-coverage duplex error-corrected WGS of ccfDNA, achieving 7.7x10-8 error rates, to assess disease burden in melanoma and urothelial cancer patients without matched tumor sequencing. Together, we show that deeply sequenced error-corrected WGS accurately calls somatic variants, demonstrating the feasibility of WGS for tumor-informed and tumor-agnostic ctDNA detection.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-19T11:24:47.146197+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000845","title":"T-bet+ CXCR3+ B cells drive hyperreactive B-T cell interactions in multiple sclerosis","description":"scRNAseq, VDJseq and methylome of non-proliferating and autoproliferating B cells from HDs and MS patients, as well as snRNAseq of highly inflamed meningeal MS brain tissue datasets that have been generated and analyzed for the study \"T-bet+ CXCR3+ B cells drive hyperreactive B-T cell interactions in multiple sclerosis\". ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-17T12:40:09.803794+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000846","title":"Long-read whole genome sequencing as a tool for variant detection in inherited retinal dystrophies","description":"WGS sequencing using nanopore long reads sequencing. These data is used for the diagnosis of patients with inherited retinal dystrophies.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-23T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000847","title":"PRPH2-Related Retinal Dystrophies: Mutational Spectrum in 103 Families from a Spanish Cohort","description":"Various NGS experiments from patients affected by genomic variants at gene PRPH2, one of the most frequently inherited retinal dystrophy (IRD)-causing genes.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[38474159],"external_links":null,"is_released":true,"released_date":"2025-04-22T13:04:53.965725+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000848","title":"DNA sequencing of sgRNAs enriched from the CRISPR-Cas9 screened HCC organoids","description":"Project aims to find enriched or depleted sgRNAs to identify functional genes in HCC progression and lenvatinib resistance","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-08T15:14:01.878026+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000849","title":"Long-read RNA sequencing of human normal liver organoid with or without SF3B4 overexpression","description":"Project aims to find alternative splicing events and resulting transcript isoforms modulated by SF3B4","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-08T15:14:01.878026+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000850","title":"RIP-seq of SF3B4 binding RNA fragments","description":"Project aims to characterize SF3B4 binding RNA fragments within liver organoids to understand its role in splicing regulation","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-08T15:14:01.878026+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000851","title":"Short-read mRNA sequencing of human normal liver organoid with or without SF3B4 overexpression","description":"Project aims to find alternative splicing events and resulting transcript isoforms modulated by SF3B4","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-08T15:14:01.878026+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000852","title":"Combined immunodeficiency caused by a heterozygous variant in the RNA binding protein Roquin-1 (RC3H1)","description":"In this study we describe a single dominant negative gene change in RC3H1, encoding the transcriptional repressor Roquin-1, causing combined immunodeficiency with autoimmune features, hyper-inflammation, lymphoproliferation, and severe infections. VCF file from proband WES data are deposited.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000853","title":"DIS3 licenses B cells for physiological plasma cell differentiation in humans","description":"DIS3 licenses B cells for physiological plasma cell differentiation in humans","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-17T10:00:36.134948+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000854","title":"Long-read RNA sequencing of human normal colon organoids and colorectal cancer organoids","description":"Project aims to measure the landscape of alternative splicing events in human normal colon organoids and CRC organoids","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000855","title":"Picuris Pueblo oral history and genomics reveal continuity in US Southwest","description":"Following the decision of Picuris Pueblo to study their population history using DNA, this project generated 16 ancient and 13 present-day genomes from the Pueblo, spanning 1,000 years of history.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-26T18:42:11.534344+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000856","title":"Neoadjuvant immune checkpoint blockade in mismatch-repair proficient colon cancers","description":"Immune checkpoint blockade has led to paradigm shifts in the treatment of various tumour types, yet limited efficacy has been observed in patients with metastatic mismatch-repair proficient (pMMR) colorectal cancer. Here we report an in-depth analysis of patients with early-stage pMMR colon cancer from the phase II NICHE study (ClinicalTrials.gov: NCT03026140). A total of 31 patients received neoadjuvant treatment of nivolumab plus ipilimumab followed by surgery. The response rate was 26% and included six patients with a major pathological response (≤10% residual viable tumour). One patient with an ongoing clinical complete response did not undergo surgery. Responses were observed despite a low tumour mutational burden in all tumours, while chromosomal genomic instability scores were significantly higher in responders compared to non-responders. Responding tumours were more likely to be TP53 mutant, KRASG12 wildtype and had significantly higher baseline expression of proliferation signatures and TCF1. Imaging mass cytometry also revealed a higher percentage of Ki-67+ cancer and Ki-67+ CD8+ T cells in responders compared to non-responders. Meanwhile, in non-responders, we observed an enrichment for an inflamed-fibrotic microenvironment associated with TGF-β expression, hinting towards possible resistance mechanisms. These results provide a comprehensive analysis of response to neoadjuvant ICB in early-stage pMMR colon cancers and identify potential biomarkers for patient selection.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-17T11:59:34.750628+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000857","title":"Biallelic loss of function PAX4 variants are a Novel Cause of Transient Neonatal Diabetes","description":"The identification of genes in which loss of function (LoF) variants cause neonatal diabetes mellitus (NDM) can provide unique insights into the development and function of human pancreatic beta cells. We describe the identification of biallelic PAX4 LoF variants in  2 unrelated individuals with transient NDM: one due to a homozygous p.(Arg126*) PAX4 stop gain variant and a second due to a homozygous c.-352_104del 2.65kb deletion affecting the first 4 exons and promoter of the PAX4 Matched Annotation from NCBI and EMBL-EBI select transcript. We confirmed reduced transcript expression due to nonsense mediated decay for the e p.(Arg126*) variant in CRISPR-edited iPSC-derived pancreatic endoderm cells. Analysis of PAX4 binding through integration of CUT&RUN and RNA-sequencing in PAX4 depleted endocrine cells identified genes directly regulated by PAX4 involved in both pancreatic islet development and glucose-sensitive insulin secretion. The remitting and relapsing diabetes in both probands demonstrates that in contrast to mice PAX4 is not essential for the development of pancreatic beta-cells and supports differences in the requirements of functional beta-cell mass across the life-course.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000858","title":"Reticulated platelets in coronary artery disease - miRNA sequencing","description":"We performed miRNA sequencing of reticulated platelets (RPs) and mature platelets (MPs) of patients with coronary artery disease.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000859","title":"Reticulated platelets in coronary artery disease - total RNA sequencing","description":"We performed total RNA sequencing of reticulated platelets (RPs) and mature platelets (MPs) of patients with coronary artery disease.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000860","title":"Longitudinal Single-cell Genomic Analysis of Initial and Recurrent Meningioma","description":"This study investigates the genomic evolution of meningioma through single-cell whole genome sequencing analysis of paired tumor samples. We analyzed tumor tissues from initial and recurrent meningiomas from the same patients to understand clonal evolution and tumor progression. The research aims to characterize copy number alterations and genomic heterogeneity at single-cell resolution across different time points of tumor development.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-11T13:34:00.721471+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000861","title":"Autosomal dominant macular dystrophy associated with THRB: identification of new families and variants  ","description":" This study aims to refine the ophthalmologic phenotype, report a novel THRB variant, and investigate the impact of these splicing variants at the protein level.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-23T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000862","title":"Beta-catenin transcriptional activity predicts survival outcomes in patients with hepatocellular carcinoma","description":"Hepatocellular carcinoma (HCC) is the most common form of liver cancer and a major cause of cancer-related deaths worldwide. Despite the wealth of genomics data, treatment and prognosis are still dependent on clinical and pathological factors. The molecular heterogeneity characterizing HCC is denoted by the different etiology and the related array of signaling pathways involved in tumor initiation and progression. Aberrant activation of the Wnt/-catenin pathway is among the most frequent alterations in HCC, and stems from somatic mutations, functional over-activity of the transcription machinery and epigenetic cues. By combining targeted DNA and RNA sequencing, we have identified a Wnt/-catenin-related transcriptional signature denoting pathway activity regardless of the presence of pathway-related activating mutations. This model predicts survival outcomes in two independent cohorts of HCC patients (TCGA cohort, N=177; Rome cohort, N=81) and is associated with distinctive immunogenomic features, denoting an immune-excluded tumor immune microenvironment.","abstract":null,"study_type":"Synthetic Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000863","title":" Evolving epigenomics of immune cells in type 1 diabetes at single nuclei resolution","description":"The appearance of diabetes-associated autoantibodies is the first detectable sign of the disease process leading to type 1 diabetes (T1D). Evidence suggests that T1D is a heterogenous disease, where the type of antibodies first formed imply subtypes. Here, we followed 49 children, who subsequently presented with T1D and 49 matched controls, profiling single-cell epigenomics at different time points of disease development. Quantitation of cell and nuclei populations as well as transcriptome and open-chromatin states indicated robust, early, replicable monocyte lineage differences between cases and controls, suggesting heightened pro-inflammatory cytokine secretion early among cases. The order of autoantibody emergence in cases showed variation across lymphoid and myeloid cells, potentially indicating cellular immune response divergence. The strong monocytic lineage representation in peripheral blood immune cells before seroconversion and the weaker differential coordination of these gene networks close to clinical diagnosis emphasizes the importance of early life as a critical phase in T1D development.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-02T14:48:45.457501+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000864","title":"metastatic uveal melanoma tumour biopsies","description":"Tumour biopsies were obtained from uveal melanoma patients pre and 16 days post treatment with tebentafusp. Biopsies, which were either snap frozen or put in RNA later, were analysed by bulk RNA sequencing (50 million reads per sample) using the Illumina NovaSeq system.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-18T16:52:11.292066+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000865","title":"smallRNA-seq of isolated pancreatic islets","description":"In this study we performed smallRNA-sequencing, a sequencing method designed for small noncoding RNAs, to investigate the miRNA expression profile of human islets isolated from pancreata of donors without diabetes mellitus (n=3) and donors with type 2 diabetes (n=3).","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-26T18:49:56.952323+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000866","title":"Transcriptomic changes in amniotic fluid associated with the fetal inflammatory response","description":"The fetal inflammatory response (FIR) increases the risk of perinatal brain injury, particularly in extremely low gestational age newborns (ELGANs, < 28 weeks of gestation). Most FIR cases are subclinical, i.e., usually FIR does not trigger observable symptoms in the mother beyond those associated with premature birth. The study of transcriptomic changes asssociated with FIR in amniotic fluid could help finding new clinical actionable FIR biomarkers.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-03T15:08:05.932561+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000867","title":"TIRE-seq: an Integrated Sample Extraction and Transcriptomics Workflow for High Throughput Perturbation Studies","description":"TIRE-seq is a novel RNA sequencing method that integrates mRNA purification directly into library preparation, eliminating separate RNA extraction. The technique demonstrated utility across three biological applications, including capturing transcriptional changes in human T cells, identifying genes driving murine dendritic cell differentiation, and analyzing the dose-response effects of temozolomide on patient-derived neurospheres. With its simplified approach and high sequencing efficiency, TIRE-seq offers a cost-effective solution for large-scale gene expression studies.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-18T16:49:19.608184+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000868","title":"Nicotinamide phosphoribosyltransferase is an integrator of circadian clock regulation and NAD+ metabolism in liver cancer","description":"NAMPT is a liver-specific integrator of circadian and metabolic regulation, and its dysregulation creates a therapeutic window for a more precise treatment of liver cancer. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-25T14:10:50.368766+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000869","title":"The Precision Medicine in Liver Cancer across an Asia-pacific NETwork (PLANET) – HCC recurrence cohort","description":"Hepatocellular carcinoma (HCC) is a highly fatal cancer marked by significant intra-tumor heterogeneity (ITH). Given 50% to 70% of HCC patients experience recurrence, understanding the origins and progression of recurrence is crucial. To address this, we assembled a multi-sector, paired HCC recurrence cohort of 24 patients, including comprehensive whole genome sequencing and transcriptome samples. Through this longitudinal cohort, we aimed to trace the origins of recurrence and identify molecular features associated with early recurrence. These insights may improve predictions of early HCC recurrence and inform potential therapeutic strategies.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-25T14:10:50.368766+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000870","title":"Clonal hematopoiesis in metastatic urothelial and renal cell carcinoma","description":"This study aimed to determine the prevalence and clinical relevance of clonal hematopoiesis in metastatic urothelial and renal cell carcinoma.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-01T13:50:17.340551+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000871","title":"Feasibility study of enzymatic methylation sequencing of cell-free DNA from cerebrospinal fluid of pediatric brain tumors for classification","description":"Array-based DNA methylation profiling is the gold standard for molecular classification of brain tumors. However, it relies on significant amount of input DNA extracted from surgical tissue, thus limiting its use for tumors where biopsy is challenging or limited in quantity. Cell-free tumor DNA (cfDNA) in cerebrospinal fluid (CSF) presents alternative opportunities for brain tumor diagnosis and disease monitoring following treatment. Novel enzymatic DNA methylation sequencing (EM-seq) methods may allow us to overcome input DNA limitations and accurately quantify methylation from cfDNA for tumor classification.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-30T08:32:26.025494+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000872","title":"Epigenetic and transcriptional profile of memory B cells in Multiple sclerosis","description":"Methylome and transcriptome data of non-proliferating and autoproliferating memory B cells (CD27+) from Multiple sclerosis patients under natalizumab treatment, that have been generated and analyzed for the study \"T-bet+ CXCR3+ B cells drive hyperreactive B-T cell interactions in multiple sclerosis\". \r\nAim is to understand epigentic and transcriptional differences in activated memory B cells in MS and how epigentic differences translated in transcriptional changes in the same patient.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-18T08:16:48.994751+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000873","title":"A Comprehensive Genetic Study of Classical Hodgkin Lymphoma Using Circulating Tumour DNA","description":"This study on classical Hodgkin lymphoma (cHL) used advanced methods to analyse circulating tumour DNA (ctDNA) in 297 cases, offering insights into its genetic landscape and linking it to disease pathophysiology and clinical progression. Key findings include the identification of whole genome duplication as a predictor of poor chemotherapy response. Additionally, a highly recurrent somatic expression quantitative trait locus of the BCL6 gene was discovered, implicating regulatory mutations in cHL pathophysiology and highlighting BCL6 as both a vulnerability and therapeutic target. Consensus clustering identified two cHL subtypes distinguished by the underlying mechanisms of genetic instability, rather than by specific genetic mutations or EBV infection. The study also linked the number and clonality of neoantigens with tumour microenvironment and response to checkpoint blockade. Finally, our results suggested ctDNA analysis as a tool to distinguish ambiguous PET/CT-positive lesions persisting after treatment, aiming to reduce unnecessary medical interventions.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-07T14:10:31.975899+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000874","title":"Effects of Metformin on Transcriptomic and Metabolomic Profiles in Breast Cancer Survivors Enrolled in the Randomized Placebo-Controlled MetBreCS Trial","description":"Metformin reduces the incidence of breast cancer in patients with obesity and type 2 diabetes. However, our knowledge of the effects of metformin on breast cancer recurrence is limited. Within the randomized double-blind placebo-controlled phase II trial MetBreCS, we examined changes in breast tissue from breast cancer survivors with BMI >25 kg/m2 after treatment with metformin. To identify metformin-regulated signaling pathways, we integrated the transcriptomic, metabolomic and steroid hormone profiles using bivariate and functional analyses. We identified MS4A1, HBA2, MT-RNR1 and MT-RNR2 expression to be differentially expressed in breast tissues from metformin-treated women. We also found metformin-associated down-regulation of EGFL6 and FDCSP in postmenopausal women. The integration of transcriptomic and metabolomic profiles revealed down-regulation of immune response genes associated with reduced levels of arginine and citrulline in the metformin-treated group. The integration of transcriptomic and steroid hormone profiles showed an enrichment of steroid hormone biosynthesis and metabolism pathways with highly negatively correlated CYP11A1 and CYP1B1 expression in breast tissue from postmenopausal metformin-treated women. Our results indicate that breast cancer survivors treated with metformin have specific changes in breast tissue gene expression that may prevent the development of new tumors.\r\n \r\nWithin the randomized double-blind placebo-controlled phase II trial MetBreCS, we examined changes in breast tissue from breast cancer survivors with BMI >25 kg/m2 after treatment with metformin using bulk RNAseq (total mRNA sequencing), that is deposited in Federated EGA. The steroid hormones, and metabolomics and the insulin sensitivity serum biomarker data underlying this article may be shared upon reasonable request to the PI of the MetBreCS study (Dr. Bernardo Bonanni), following approval by the Data and Safety Monitoring Board at IEO, Milan. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-02-21T08:43:03.377956+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000875","title":"APOBEC3 mutagenesis drives therapy resistance in breast cancer","description":"Acquired genetic alterations commonly drive resistance to endocrine and targeted therapies in metastatic breast cancer, however the underlying processes engendering these diverse alterations are largely uncharacterized. To identify the mutational processes operant in breast cancer and their impact on clinical outcomes, we utilized a well-annotated cohort of 3,880 patient samples with paired tumor-normal sequencing data. The mutational signatures associated with apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) enzymes were highly prevalent and enriched in post-treatment compared to treatment-naïve hormone receptor-positive (HR+) cancers. APOBEC3 mutational signatures were independently associated with shorter progression-free survival on antiestrogen plus CDK4/6 inhibitor combination therapy in patients with HR+ metastatic breast cancer. Whole genome sequencing (WGS) of breast cancer models and selected paired primary-metastatic samples demonstrated that active APOBEC3 mutagenesis promoted resistance to both endocrine and targeted therapies through characteristic alterations such as RB1 loss-of-function mutations. Evidence of APOBEC3 activity in pre-treatment samples illustrated a pervasive role for this mutational process in breast cancer evolution. The study reveals APOBEC3 mutagenesis to be a frequent mediator of therapy resistance in breast cancer and highlights its potential as a biomarker and target for overcoming resistance.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-02T14:57:17.788035+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000876","title":"SATB1 KO Treg and Teff cells: ATAC-seq","description":"To study the global effects of SATB1 on gene networks in fully differentiated, ex vivo expanded human CD4 T effector cells and Treg cells, we performed ATAC-seq. We systematically assessed the impact of SATB1 on the chromatin levels in mature human Treg and CD4 T effector cells.  ","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-04T15:41:53.385005+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000877","title":"SATB1 KO Treg and Teff cells: RNA-seq","description":"To study the global effects of SATB1 on gene networks in fully differentiated, ex vivo expanded human CD4 T effector cells and Treg cells, we performed bulk RNA-seq. We systematically assessed the impact of SATB1 on the mRNA levels in mature human Treg and CD4 T effector cells.  ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-04T15:41:56.172257+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000878","title":"CARE iSGS single nucleus RNA-seq","description":"This study contains single nucleus RNA-sequencing data from healthy controls, iSGS, and traumatic subglottic stenosis patients.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-03T15:12:36.785702+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000879","title":"CARE idiopathic subglottic stenosis bulk transcriptomics. ","description":"Idiopathic subglottic stenosis (iSGS) is a severe chronic orphan disease characterised by recurrent scarring of the subglottis, predominantly affecting Caucasian females in their fourth to sixth decade of life. Due to its rarity, understanding the clinical trajectory and molecular factors involved in iSGS disease development and prognosis has been challenging. In this study, we prospectively enrolled patients with iSGS, trauma-induced subglottic stenosis, and controls to investigate the clinical, transcriptional, and genetic features that may be associated with disease pathogenesis and treatment outcomes. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-03T15:12:33.85834+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000880","title":"Cambridge Neoadjuvant Cancer of the Prostate (CANCAP03): A Window Study into the Effects of Olaparib ± Degarelix in Primary Prostate Cancer.","description":"Study: Cambridge Neoadjuvant Cancer of the Prostate (CANCAP03): A Window Study into the Effects of Olaparib ± Degarelix in Primary Prostate Cancer.\r\n \r\nEudraCT Number: 2014-004417-86\r\nClinicaltrials.gov Number: NCT02324998\r\n \r\nPurpose: Investigate combined PARP and androgen inhibition in primary prostate cancer.\r\n \r\nAim: To understand the biological mechanism(s) underlying clinical efficacy, especially in the absence of mutations in homologous recombination (HR) repair pathways.\r\n \r\nDataset: Single-nuclear RNA sequencing data from post-treatment radical prostatectomy tissue cores for six patients, 3 from each of olaparib and olaparib and degarelix cohorts.\r\nSamples were processed for nuclear isolation and extraction, prior to single-nuclear RNA sequencing. 10x libraries were constructed using the 10x supplied protocol, briefly: individual nuclei were trapped into droplets with a single bead, and poly A transcripts were barcoded during reverse transcription. Complementary DNA was amplified, and libraries were prepared for sequencing on NovaSeq 6000 using S4 flow cell (100k reads per cell). FASTQ files were processed using CellRanger pipeline (10X Genomics). Outputs from the CellRanger pipeline were analysed using the Seurat package (v4.9.9.9049) in R (v4.2.0).\r\nProcessed data is provided as a Seurat object.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-21T16:40:25.279251+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000881","title":"Single-cell RNA-seq of  immune cells from human tumor fragments","description":"Tumor-reactive T cells are key effectors of the antitumor response elicited by PD-1 blockade. However, intratumoral T cells are often rendered dysfunctional, and it remains elusive how this treatment initiates T cell-driven antitumor immunity in cancer tissues. To address this, we dissected the early T cell reactivation following anti-PD-1 in human tumor tissue explants. Using bispecific antibodies to selectively target PD-1 blockade to individual T cell subsets, we demonstrate that both intratumoral CD8+ and CD4+ T cells can independently drive immune responses to anti-PD-1 therapy. These tumor-specific CD8+ and CD4+ T cells exhibit a shared dysfunctional gene program with characteristics of terminal exhaustion and high effector gene expression but impaired translational capacity. Of note, PD-1 blockade reinvigorates such late-dysfunctional T cells in cancer tissues by overcoming this translational barrier rather than via transcriptional rewiring, resulting in restored effector function and potent downstream immune responses. Altogether, these results challenge the current view of terminally differentiated dysfunctional T cells as inert cells lacking therapeutic potential and position them as key initiators of the early tissue response to PD-1 blockade.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000882","title":"Single-cell RNA-seq of  immune cells from human tumor fragments  after 48 hour culture ex vivo (Kaptein et al., 2024)","description":"Tumor-reactive T cells are key effectors of the antitumor response elicited by PD-1 blockade. However, intratumoral T cells are often rendered dysfunctional, and it remains elusive how this treatment initiates T cell-driven antitumor immunity in cancer tissues. To address this, we dissected the early T cell reactivation following anti-PD-1 in human tumor tissue explants. Using bispecific antibodies to selectively target PD-1 blockade to individual T cell subsets, we demonstrate that both intratumoral CD8+ and CD4+ T cells can independently drive immune responses to anti-PD-1 therapy. These tumor-specific CD8+ and CD4+ T cells exhibit a shared dysfunctional gene program with characteristics of terminal exhaustion and high effector gene expression but impaired translational capacity. Of note, PD-1 blockade reinvigorates such late-dysfunctional T cells in cancer tissues by overcoming this translational barrier rather than via transcriptional rewiring, resulting in restored effector function and potent downstream immune responses. Altogether, these results challenge the current view of terminally differentiated dysfunctional T cells as inert cells lacking therapeutic potential and position them as key initiators of the early tissue response to PD-1 blockade.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000883","title":"miRNA sequencing of HUVECs in hypoxia conditions, with separation of the nuclear and cytosolic compartments.","description":"We study miRNA expression in HUVECs, in the context of hypoxia within the nuclear and cytosolic fraction, separately. Through comparison of miRNA sequencing processing methods (including the commonly used methods and isomiR-level analysis), to then perform differential expression, we show that including isomiRs in miRNA analysis adds diversity, resolution, power and alleviates some of the shortcomings and biases that we highlight. Our study demonstrates the interest of including isomiRs when studying cellular-context dependent miRNA expression changes.\t\t\t\t\t","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000884","title":"The Multiomics Blueprint of the Individual with the Most Extreme Lifespan","description":"Although centenarians are becoming more common in the demography of human populations, the so-called supercentenarians (over 110 years old) are still a rarity. In Catalonia, the historic nation where the subject lived, the life-expectancy for women is 86 years old, so she exceeded more than 30 years the mean statistical value. In a similar manner that premature aging syndromes, such as Hutchinson-Gilford Progeria and Werner syndrome, can provide relevant clues about the mechanisms of aging; the study of supercentenarians might also shed light in the pathways involved in lifespan. To unfold the biological properties that exhibited such a remarkable human being, we developed a comprehensive multiomics analysis in different tissues of her genomic, transcriptomic, metabolomic, epigenomic and microbiomic landscapes , comparing the results with those observed in non-supercentenarian populations.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-11T17:30:55.646664+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000885","title":"Tumor Profiler Ovarian Study","description":"The Tumor Profiler Study is an observational trial combining a prospective diagnostic approach to assess the relevance of in-depth tumor profiling to support clinical decision-making with an exploratory approach to improve the biological understanding of the disease. Technologies used are digital pathology, targeted NGS, single-cell RNA, single-cell DNA, bulk RNA, bulk proteotyping, single-cell CyTOF, imaging mass cytometry, pharmacoscopy, 4i Drug Response Profiling, and cell-free DNA.\r\nThese technologies were applied to 240 tumor samples collected over 3 years across three cancer indications: metastatic melanoma, metastatic epithelial ovarian cancer, and acute myeloid leukemia (AML).\r\nHere, we publish the scRNA and scDNA data of the ovarian cancer cohort.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-26T11:53:39.469631+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000886","title":"Hofer et al., A specific subpopulation of cancer-associated fibroblasts promotes resistance to chemotherapy in triple-negative breast cancer by upregulating G0S2 protein","description":"Chemotherapy is the standard of care for patients with triple-negative breast cancer (TNBC), but the mechanisms of chemoresistance remain poorly understood. Here, we investigated the role of cancer associated fibroblasts (CAFs) in the chemotherapy response of TNBC, by combining in vivo analyses of TNBC patients with ex vivo cancer modeling, using tumor-on-chip (ToC) technology. Transcriptomic analysis revealed that the proportion of a specific CAF population, the extracellular matrix-producing myofibroblasts (ECM-myCAFs), is reduced after chemotherapy in chemo-sensitive, but not in chemo-resistant TNBC patients. In ToC devices, primary ECM-myCAFs promoted TNBC cell survival under Doxorubicin and Paclitaxel treatment. The mechanism of chemoresistance was elucidated by using single-cell RNA sequencing, advanced cell imaging and functional assays: ECM-myCAFs upregulate the G0/G1 switch 2 (G0S2) protein in TNBC cells, via activation of SRC family kinases. Altogether, our work identifies G0S2 as a new player in CAF mediated chemotherapy resistance in TNBC.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-06T15:33:55.307067+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000887","title":"Discovery and validation of an ancillary genomic test of malignancy for primary melanocytic tumors","description":"Background:Pathological diagnosis of melanocytic tumors can be difficult and prone to error. More accurate and reliable ancillary investigations than those currently available are required to improve diagnostic accuracy.\r\n\r\nGoals: (1) to generate a genomic model for distinguishing benign (nevi) from malignant (melanoma) melanocytic skin tumors, developed from a customized gene panel evaluated on a cohort of 250 nevi and melanomas. (2) To evaluate the performance of the genomic model in melanocytic tumors of uncertain diagnosis/behavior. \r\n\r\nDetails: The cohort of 250 melanomas and naevi was split into a discovery set and a validation set. Our genomic model obtained an area under the curve of 95% in the discovery cohort and 96% for the validation cohort. Based on a Youden index threshold, the resulting classifier shows high specificity (>95% in the discovery and validation cohorts), with sensitivities >80% in the discovery and validation cohorts. Evaluation of the genomic model on a cohort of 110  melanocytic tumors identifies key driver mutations in agreement with the likely pathway of origin of the tumors. The probability of melanoma (p=0.02) from the genomic model was significantly associated with pathology-based estimates of malignancy for melanocytic tumors lacking pathway-defining genomic aberrations (conventional tumors). The genomic model identified 8/36 (22%) conventional tumors with unresolved malignancy to have a high probability of melanoma, with 7/8 of these cases showing negative/non-aberrant results with either fluorescent in-situ hybridization, PRAME and/or p16 immunostains. Furthermore, no evidence of malignant behavior based on the genomic model was seen in 4 conventional borderline tumors with more than 1 year follow-up. \r\n\r\nConclusion: This genomic model can become a clinically useful ancillary tool that is highly specific for differentiating melanomas from nevi. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-26T10:11:50.805467+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000888","title":" Single cell transcriptomics to characterize the tumor microenvironment of prostate cancer fusion biopsies ","description":"The primary objective of this study was to characterize the tumor microenvironment in fusion-guided transperineal biopsy samples from patients undergoing PC diagnosis. For each patient, one biopsy was taken from a suspected tumor region and another from a non-suspicious area, which were later classified as high- or low-tumorigenicity based on anatomopathological analysis. \r\n\r\nUsing scRNA-seq data, we performed cancer-oriented cell annotation, differential expression analysis, and functional pathway enrichment studies across key cellular subpopulations. Additionally, differential abundance analysis was conducted to identify cell groups representative of different tumorigenicity levels. Finally, classification models were developed using gene expression data to differentiate high- vs. low-tumorigenicity samples, with the long-term goal of establishing a diagnostic classifier for PC stratification. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-20T17:11:44.708263+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000889","title":"Splicing signature analysis of RNU4-2, RNU5A-1 and RNU5B-1","description":"Pathogenic variants in the snRNA RNU4-2 were recently described as a frequent cause of neurodevelopmental disorders. In our study we further delineate the phenotype associated with RNU4-2 and we also identify pathogenic variants in RNU5A-A and RNU5B-1. Capture-based RNA-Seq were performed to compare splicing pattern between affected and control individuals. A strong signature based on alternative 5' splice site usage was found for RNU4-2 patients, and we suggest an either 5' or 3' signature depending on the variant's localiztion in U5 genes.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-11T09:23:48.027115+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000890","title":"Clonal hematopoiesis in rheumatoid arthritis","description":"To evaluate the clinical impact of CHIP on RA phenotypes and outcomes, we collected DNA samples from four distinct RA patient cohorts of newly diagnosed, previously untreated, RA patients without hematologic malignancies. A total of 573 RA patients and 163 healthy controls underwent targeted NGS sequencing using a sequencing panel consisting of 65 genes recurrently mutated in myeloid malignancies.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-27T12:19:13.543903+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000891","title":"Synchronous patterning of hiPSC-derived CNS progenitors generates comprehensive axial spinal cord organoids (CASCOs) containing diverse motor neuron population","description":"Advancements in human induced pluripotent stem cell (hiPSC) culture have enabled the generation of spinal cord organoids (SCOs), though achieving distinct axial identities in spinal motor neurons (spMNs) along the rostro-caudal (RC) axis remains a challenge. By optimizing the timing and sequence of patterning factors, we developed a mixed stem cell model of rostral neural stem cells (NSCs) and caudal neuromesodermal progenitors (NMPs) to generate SCOs with enhanced spMN heterogeneity, including a wide range of axial identities and benchmarked this against commonly used protocols. Our approach, termed CASO (Comprehensive Axial Spinal Organoids), also incorporates endothelial networks and skeletal muscle to improve organoid complexity and health, offering a novel method to study spMN axial specification and model neurodegenerative diseases.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-27T11:46:33.294747+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000892","title":"Human papillomavirus integration induces oncogenic host gene fusions in oropharyngeal cancers","description":"HPV integration disrupts host genomic structure and expression, but whether these alterations promote cancer development remains unclear. Multiple genomic analyses of oropharyngeal cancers identified several host gene fusions, including recurrent FGFR3-TACC3 fusions, expressed from rearranged genomic loci adjacent to HPV integration sites.  Evolutionary modeling implicated integration of virus concatemers into the host genome as a common initiating event in fusion formation. Co-expression of HPV16 E6/E7 and FGFR3-TACC3, but neither alone, was sufficient for tumor development in both xenograft and syngeneic mouse models and led to unique transcriptional programs implicated in carcinogenesis. FGFR3-TACC3 expression decreased the ubiquitination and degradation of E6 and E7, thereby increasing oncoprotein abundance. We conclude that expression of HPV16 oncoproteins and host gene fusions generated from HPV integration sites can be sufficient for cancer development.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-14T15:49:56.461561+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000893","title":"Oropharynx cancers sequencing study (RNA-seq from FFPE)","description":"This is a study of transcriptomics in HPV-associated oropharynx tumors. The goals of this study were to characterize HPV+ oropharynx tumor subtypes and to examine HPV integration events and their downstream effects. HPV-host fusion transcripts and recurrent HPV integration genes were identified. Various alternative isoforms and splicing events of HPV genes were also studied. Multiple potential biomarkers of prognosis were associated with clinical outcomes.","abstract":null,"study_type":"RNASeq","pubmed_ids":[39026719],"external_links":null,"is_released":true,"released_date":"2025-10-30T17:20:33.917749+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000894","title":"Context-specific regulatory genetic variation in MTOR dampens neutrophil-T cell crosstalk in pneumonia-associated sepsis, modulating disease","description":"Sepsis is a heterogeneous clinical syndrome with a high mortality, requiring personalised stratification strategies. Here, we characterise genetic variation that modulates MTOR, a critical regulator of metabolism and immune responses in sepsis. The effects are highly context specific, involving a regulatory element that affects MTOR expression in activated T cells with opposite direction of effect in neutrophils. We show that the G-allele of the lead variant, rs4845987, associated with decreased risk of T2D, reduces MTOR expression in T cells and improves survival in sepsis due to pneumonia, with effects specific to sepsis endotype. Using ex vivo models, we demonstrate that activated T cells promote immunosuppressive sepsis neutrophils through released cytokines, a process dampened by hypoxia and the mTOR inhibitor rapamycin. Our work demonstrates a novel epigenetic mechanism that fine-tunes MTOR transcription and T cell activity via the variant-containing regulatory element, which further exhibits an allelic effect upon vitamin C treatment. These findings reveal how genetic variation interacts with disease state to modulate immune cell-cell communication, providing a patient stratification strategy to inform more effective sepsis treatment.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-04T16:09:06.818313+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000895","title":"HIV-phyloTSI: Subtype-independent estimation of time since HIV-1 infection for cross-sectional measures of population incidence using deep sequence data","description":"Estimating the time since HIV infection (TSI) at population level is essential for tracking changes in the global HIV epidemic. Most methods for determining TSI give a binary classification of infections as recent or non-recent within a window of several months, and cannot assess the cumulative impact of an intervention. We developed a Random Forest Regression model, HIV-phyloTSI, which combines measures of within-host diversity and divergence to generate continuous TSI estimates directly from viral deep-sequencing data, with no need for additional variables. HIV-phyloTSI provides a continuous measure of TSI up to 9 years, with a mean absolute error of less than 12 months overall and less than 5 months for infections with a TSI of up to a year. It performs equally well for all major HIV subtypes based on data from African and European cohorts. We demonstrate how HIV-phyloTSI can be used for incidence estimates on a population level.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-15T12:03:10.837348+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000896","title":"Lung cancer Early Molecular Assessment","description":"This study aimed to validate the potential utility of a clinically accessible, highly sensitive tumor-informed circulating tumor DNA (ctDNA) assay. The study considers a ‘landmark’ time period (between two weeks and four months after definitive treatment), as well as longitudinal sampling (>2 weeks) and compares two independent, retrospectively collected real-world cohorts.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-11T13:19:19.347097+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000897","title":"The function of circular RMST in neuroendocrine tumours","description":"Circular RNA (circRNA) is a class of noncoding RNA with regulatory potentials. Its role in the transdifferentiation of prostate and lung adenocarcinoma into neuroendocrine prostate cancer (NEPC) and small cell lung cancer (SCLC) remains unexplored. Here we identified circRMST as an exceptionally abundant circRNA predominantly expressed in NEPC using total RNA-seq profiling of patient samples. In addition, circRMST is also abundantly expressed in SCLC. Functional studies using shRNA, siRNA, CRISPR-Cas13 and Cas9 consistently demonstrate that circRMST is essential for tumour growth and the expression of ASCL1, a master regulator of neuroendocrine fate. Mechanistically, circRMST physically interacts with lineage transcription factors NKX2-1 and SOX2. Loss of circRMST induces NKX2-1 protein degradation through autophagy-lysosomal pathway and alters the genomic binding of SOX2, collectively leading to the loss of ASCL1 transcription. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-11T13:17:19.698507+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000898","title":"Single-Cell Immune Profiling in Ovarian Germ Cell and Sex Cord-Stromal Tumours","description":"The immune microenvironment of ovarian germ cell tumours (OGCT) and sex-cord stromal tumours (SCST) is unexplored. To better understand their immune landscape, we constructed a blueprint using single-cell RNA sequencing (scRNA-seq). We performed scRNA-seq of twelve tumour samples: seven adult granulosa cell tumour (aGSCT), one juvenile GSCT (jGSCT) and one Sertoli-Leydig (SL) tumour, two immature teratoma (IT) and one dysgerminoma (DG). We characterised immune cell subtypes based on their specific marker genes. We constructed a detailed blueprint of the immune microenvironment of OGCT and SCSTs, elucidating potential modulators that shape their immune landscape. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000899","title":"Effects of KSP inhibitor filanesib in aggressive hepatoblastoma PDX cells ","description":"Aim of this RNA sequencing dataset has been to asses effects caused by the KSP inhibitor filanesib in aggressive hepatoblastoma PDX cells. Two cell lines (HB-279 and HB-284) were utilised. DMSO-treated cells were used as controls. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-16T11:09:53.196986+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000900","title":"Arcagen - Gynecologic cancer domain","description":"Arcagen is an EORTC/SPECTA pan-European project that aims to recruit 1000 rare cancer patients from different tumour domains of EURACAN. This study collected samples from advanced or metastatic rare cancer from patients older than 12, and analysed them using Foundation Medicine next-generation sequencing (NGS) panels (FoundationOne CDx for FFPE samples or FoundationOne Liquid CDx for blood samples). Here we are submitting the dataset that contain NGS files from patients with rare ovarian cancer and primary peritoneal cancer and/or fallopian-tube cancer, including low grade serous carcinoma, mucinous adenocarcinoma, clear cell adenocarcinoma; and other rare cancers such as sex cord tumors, germ cell tumor, yolk sac tumor, and malignant/immature teratoma (n=94).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-02T14:17:20.784892+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000901","title":"McQuillin_Global_WES_Schizophrenia","description":"Whole Exome Sequencing of Schizophrenia cases and matched controls performed at the Broad Institute on a cohort from UCL, London, UK","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-04T09:16:36.408543+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000902","title":"Direct genetic transformation bypasses tumor-associated DNA methylation alterations","description":"Tumors represent dynamically evolving populations of mutant cells, and many advances have been made in understanding the biology of their progression. However, key unresolved questions remain about the conditions that support their initial transformation, which cannot be easily captured in patient populations but are instead modeled using transgenic cellular or animal systems. Here, we used extensive patient atlas data to define common features of the tumor DNA methylation landscape as they compare to healthy human cells and used this benchmark to screen 21 engineered human and mouse models for their ability to reproduce these patterns. Notably, we find that genetically induced cellular transformation can trigger global changes in DNA methylation levels that are consistent with extensive proliferation but rarely recapitulate the widespread de novo methylation of Polycomb targets as found in clinical samples. Our results raise pertinent questions about the relationship between genetic and epigenetic aspects of tumorigenesis and provide an important molecular reference for evaluating existing as well as newer tumor models. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-06T15:58:47.62441+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000903","title":"GEOCODE Cohort","description":"We built a large cohort of 406 healthy individuals and expanded the immune cis-regulome through their whole blood transcriptome obtained after stimulation with specific toll-like receptor (TLR) agonists and T-cell receptor (TCR) antagonist","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-26T09:48:47.270034+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000904","title":"Deciphering the complex clonal heterogeneity of polycythemia vera and the response to interferon alpha","description":"We integrated colony formation and differentiation assays with single-cell RNA sequencing and single-cell genotyping in PV patient-derived cells vs. healthy controls to dissect how IFNa targets diseased clones during erythroid differentiation.\r\nOur findings indicate that PV-derived clones either undergo apoptosis or pass through their typical differentiation cycle, contributing to the long-term exhaustion of mutant cells in the bone marrow. The pivotal roles of ribosomal genes and clonal prerequisites in the therapeutic mechanism of IFNa are underscored by our study.\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-03-31T15:28:38.364962+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000905","title":"Comparison of transcriptomics profile of stem cell-derived beta cells from HUES8 and RC9","description":"Stem cell-derived islet cells have a potential to be used to restore endogenous insulin production in people with diabetes. The goal of this experiment is to compare the transcriptomics profile of stem-cell derived beta cells from two different cell lines: HUES8 (non-clinical grade) and RC9 (clinical grade) in terms of beta cell identity and maturity. Stem cell-derived islets were produced using differentiation protocol detailed in Rajaei et al. 2025 (manuscript approved in Science Translational Medicine, pending pubmed ID). Single cell transcriptomics data were generated using 10x Genomics 3' Single Cell Gene Expression kit.  ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-16T15:14:57.793658+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000906","title":"SweGen: a whole-genome data resource of genetic variability in a cross-section of the Swedish population","description":"The SweGen project represents a comprehensive map of genetic variation in the Swedish population. This Study contains four datasets where the first one contains whole-genome sequencing data in CRAM-format for 942 individuals from the Swedish Twin Registry, the second one contains genetic variant frequencies in VCF-format for the same individuals, the third one contains whole-genome sequencing data in CRAM-format for 58 individuals from the Northern Sweden Population Health Study and the fourth one contains genetic variant frequencies in VCF-format for the same individuals. The data, serving as a reference dataset, is a valuable and national resource for genetics research and clinical diagnostics and can be used, for instance, to increase understanding of both rare and complex disorders. It also serves as an international resource for larger studies of human population genetics.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[28832569],"external_links":null,"is_released":true,"released_date":"2025-04-04T14:16:26.891492+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000907","title":"Targeted proteomics for endotyping of chronic rhinosinusitis","description":"To identify biomarkers allowing for the distinction between different chronic rhinosinusitis patient groups and disease controls (n=20 of each DC, CRSsNP, CRSwNP and N-ERD), we use high-throughput targeted proteomics (Olink Multiplex platform) in nasal secretions and serum samples.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-02T09:01:37.911348+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000908","title":"Discordant_Monozygotic_Twins_ALS(Genetics)","description":"Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Regarding genetic factors, pathogenetic mutations in more than 35 genes have been identified as playing a role in disease pathogenesis. However, a substantial portion of ALS heritability remains unaccounted for, pointing to the potential involvement of additional genetic and epigenetic factors. For this reason, we conducted a multi-omics study on a monozygotic twin pair discordant for amyotrophic lateral sclerosis, performing whole exome sequencing, transcriptomic and epigenetic analyses to gain crucial insights into underlying pathogenetic disease mechanisms. Here, we share genetic data.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-23T16:22:52.978274+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000909","title":"Discordant_Monozygotic_Twins_ALS(Transcriptomics)","description":"Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron degeneration. Despite known genetic contributions to both familial and sporadic ALS cases, much of ALS heritability remains unexplained, suggesting the involvement of other genetic and epigenetic factors. To address this gap, we used a comprehensive multi-omics approach, in a pair of Italian monozygotic twins discordant for ALS, integrating DNA methylation, transcriptomics, and whole exome sequencing (WES). Here we share transcriptomic data derived from bulk RNA-seq on RNA extracted from PBMCs of the twin pair. This analysis revealed distinct transcriptomic profiles underlying the discordant disease phenotypes. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-23T16:22:56.00412+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000910","title":"Comprehensive Clinico-genomic Analysis of Pancreatic Ductal Adenocarcinoma: Overcoming Biases and Limitations","description":"Pancreatic ductal adenocarcinoma (PDAC) remains one of the most challenging malignancies with an\r\nexceptionally poor prognosis. Despite numerous genomic studies aimed at improving PDAC clinical\r\noutcomes, most have been constrained by biased cohort compositions (e.g., race, stage, and tissue\r\nsource) and limited clinical information. To address these limitations, we established a large-scale,\r\nunbiased genomic dataset from Asian patients with PDAC using endoscopic ultrasound-guided fine\r\nneedle biopsy. Leveraging comprehensive clinico-genomic analyses with this unique and well-organized\r\ndataset, we identified several distinct genetic features linked to diverse clinical phenotypes in PDAC.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000911","title":"Shallow whole genome sequencing of ctDNA samples from DETECT study","description":"A large-scale retrospective study in metastatic breast cancer patients using circulating tumour DNA and machine learning to predict treatment outcome and progression-free survival from the paper \"A large-scale retrospective study in metastatic breast cancer patients using circulating tumour DNA and machine learning to predict treatment outcome and progression-free survival\", by Beddowes et al. Mol.Onc.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-07T16:47:32.153519+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000912","title":"Shared disease specific B cell clones in Crohn’s disease","description":"We performed deep sequencing of the B cell receptor (BCR) repertoire in four cohorts of patients with Crohn’s disease (CD) together with healthy and disease controls. Using sequence homology, we identified BCR clones that were shared between patients with CD but not found in healthy individuals nor in patients with ulcerative colitis (UC), indicating CD-associated B cell immune responses. Shared clones were present in inflamed gut mucosa, draining intestinal lymph nodes and blood, suggesting the presence of common CD-associated antigens that drive B cell responses in CD patients.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-11T09:09:17.600417+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000913","title":"Multi-omic analyses from a randomized phase II study of epigenetic priming followed by nivolumab in previously treated metastatic non-small cell lung cancer","description":"Emergence of resistance to immune checkpoint blockade (ICB) mandates the development of strategies for ICB sensitization. We aimed to understand the effects of epigenetic priming in re-shaping the tumor microenvironment, together with molecular drivers of therapeutic response of epigenetic therapy followed by ICB in non-small cell lung cancer (NSCLC; NCT01928576).  This was done through a multi-omic approach encompassing both genomic and transcriptomic analyses. Findings suggest that epigenetic therapy may reshape the tumor microenvironment towards a more inflamed phenotype and prime responses to immunotherapy. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-29T18:59:14.252975+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000914","title":"A prospective study identifies MisMatch Repair genes as candidate predisposing genes for uveal melanoma.","description":"Objective: The aim of this study is to identify new predisposing genes for uveal melanoma (UM), the most common intraocular malignancy in adults.\r\n\r\nDesign: Prospective cohort study from Institut Curie.\r\n\r\nParticipants: 381 unselected patients diagnosed with UM between July 2021 and February 2023 at Institut Curie.\r\n\r\nMethods: All patients received genetic counseling and consented to extended genetic testing. A panel of 122 genes was analyzed by targeted sequencing on germline DNA from these patients.\r\n\r\nMain outcomes measures: UM was diagnosed by ophthalmologists at Institut Curie, and a senior pathologist confirmed the diagnosis when tumor or biopsy was available. Classification of the germline genetic variants was performed according to the ACMG guidelines.\r\n\r\nResults: We identified at least one pathogenic variant (PV) in 79 patients. Among those variants, 20 were found in clinically relevant genes for the patient’s follow-up and genetic counseling. We found a significant enrichment of germline pathogenic variants in Mismatch Repair (MMR) MLH1, MSH2 and MSH6 genes in this UM cohort, suggesting that MMR germline alterations could predispose to UM.\r\n\r\nFrom this cohort, one tumor was available from a patient carrying a MLH1 germline mutation. The tumor was characterized by a monosomy 3, in line with a loss of heterozygosity (LOH) of MLH1, located on chromosome 3. Loss of expression of MLH1 and PMS2 was observed by immunohistochemistry, and MMR mutational signatures SBS6, ID1 and ID2 were identified from the whole genome sequencing of the tumor. These data suggest that MLH1 is implicated in the oncogenesis of this UM.\r\n\r\nConclusions: This study is the largest prospective constitutional study performed on UM patients, and the first demonstrating that MMR germline alterations are significantly enriched among these patients. Further analyses will be needed to estimate the risk of developing UM for patients with Lynch syndrome","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-09T14:19:24.002862+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000915","title":"GTestimate: Improving relative gene expression estimation in scRNA-seq using the Good-Turing estimator","description":"This study introduces a novel scRNA-seq normalization method, which takes unobserved genes into account. To validate GTestimate we designed a cell targeted amplification strategy, enabling us to sequence a small set of cells twice, once at a \"typical\" sequencing depth and once at a \"ultra-deep\" sequencing depth.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-11T09:15:42.549716+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000916","title":"Circulating Tumor DNA Analysis in ERBB2-Amplified Colorectal Cancer: Biomarker Analysis of the MyPathway Trial","description":"Combination of two HER2-directed antibodies, pertuzumab and trastuzumab (P+T), has antitumor activity in HER2-positive colorectal cancer (CRC). Although liquid biopsies are increasingly being used in clinical oncology, the association between tumor and circulating tumor DNA (ctDNA) ERBB2 status and ctDNA monitoring for early response and resistance are unknown. Eighty-five patients with ERBB2-amplified and/or overexpressed CRC were treated with P+T in the MyPathway trial; 42 had ctDNA testing at Cycle 1 Day 1 (C1D1), and 38 had longitudinal plasma tested for ctDNA. We analyzed the ctDNA vs tissue ERBB2 concordance, genomic co-alterations, and ctDNA dynamics and association with response. Forty-one (98%) of 42 patients had genomic alterations detected in ctDNA at C1D1, and 29 (69%) had ERBB2 amplification in ctDNA. There was a strong correlation between ERBB2 copy number on next-generation sequencing in tissue and C1D1 ERBB2 ctDNA copy number. Thirty-seven percent achieved a molecular response by C3D1 on P+T, which was associated with prolonged progression-free survival and overall survival (OS). CDKN2A and KRAS mutations were associated with shorter OS, and a trend was seen with PIK3CA mutations. Several emerging co-alterations were identified in ctDNA at progression, including in the MAPK and PI3K pathways and other tyrosine receptor kinases. ctDNA can detect ERBB2 amplification in many, but not all, patients with ERBB2 amplification detected in tumor samples. ctDNA molecular response was associated with better survival, and ctDNA co-alterations may offer insights into mechanisms of intrinsic and acquired resistance.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-16T13:15:08.469224+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000917","title":"Enhancer profiling identifies epigenetic markers of endocrine resistance and reveals therapeutic options for metastatic castration-resistant prostate cancer patients (LuCaP cell line data)","description":"Androgen Receptor (AR) signaling inhibitors, including enzalutamide, are treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC), but resistance inevitably develops. Using metastatic samples from a prospective phase II clinical trial, we epigenetically profiled enhancer/promoter activities with H3K27ac chromatin immunoprecipitation followed by sequencing, before and after AR-targeted therapy. We identified a distinct subset of H3K27ac-differentially marked regions that associated with treatment responsiveness. These data were successfully validated in mCRPC patient-derived xenograft models (PDX). In silico analyses revealed HDAC3 as a critical factor that can drive resistance to hormonal interventions, which we validated in vitro. Critically, we identified the pan-HDAC inhibitor, vorinostat to be effective in decreasing tumor cell proliferation both in vitro and in vivo. Moreover, we uncovered evidence for HDAC3 working together with Glucocorticoid Receptor (GR) as a potential mechanism for this therapeutic effect. These findings demonstrate rationale for new therapeutic strategies including HDAC inhibitors to improve patient outcome in advanced stages of mCRPC.                       Project Goal: We identified H3K27ac regions associated with resistance in patient samples. Extensive analysis of these regions suggested that HDAC3 may play a role in resistance. To test this, we analyzed ChIP-seq and RNA-seq from cell lines generated from PDX LuCaP samples (recapitulating resistant and non-resistant) to validate findings in patient samples. ChIP-seq samples were used to verify the signals identified from specific factors, such as H3K27ac, AR, FOXA1, GR and HDAC3, their association with resistance and possible mechanisms of action. RNA-seq samples were analyzed to determine the effect of AR signaling in these samples in specific genes in the H3K27ac resistance-associated regions.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-02T14:51:20.075261+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000918","title":"Single-cell transcriptional mapping reveals genetic and hierarchy-based determinants of aberrant differentiation in AML","description":"Therapeutic targeting of acute myeloid leukemia (AML) has in part been hampered by profound cell state heterogeneity among leukemia cells. To develop a more precise understanding of leukemia cell states in AML, we constructed a reference atlas of human hematopoiesis from 263,519 single cell transcriptomes spanning 55 cellular states. Using this atlas, we mapped over 1.2 million single-cell transcriptomes spanning 318 myeloid leukemia samples. This uncovered twelve recurrent patterns of aberrant differentiation in AML and additional leukemia cell states involving lymphoid and erythroid progenitors. Systematic mapping of genotype-to-phenotype associations revealed specific differentiation landscapes associated with >45 genetic drivers. Importantly, AML samples sharing common genetic driver alterations can have distinct cellular origins which inform the cellular identity of their disease-sustaining leukemia stem cell (LSC). Further, distinct LSC-driven hierarchies can co-exist within individual patients. Thus, precise mapping of malignant cell states provides insights into leukemogenesis, refines disease classification, and informs therapy development.\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-30T11:41:54.356716+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000919","title":"The origin of post-transplant clonal hematopoiesis can be traced to prenatal development. ","description":"Clonal hematopoiesis (CH), a prevalent and premalignant state in the elderly, can occur in young individuals under selective pressures such as hematopoietic cell transplantation (HCT). However, the origin of CH and mutational processes underlying CH driver mutations in young individuals remain unclear. Here, we used genome-wide somatic mutation profiles to retrospectively trace the origin of DNMT3A-mutant CH in three individuals, 14-41 years after childhood HCT.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-01T09:37:49.777697+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000920","title":"Admixture histories of São Tomé e Príncipe.","description":"In this study, we aim to reconstruct the complex genetic admixture histories of the population of São Tomé e Príncipe, an archipelago in the Gulf of Guinea that experienced successive waves of forced and deliberate migration from Africa since the 15th century, during and after the Trans-Atlantic Slave Trade.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-16T11:16:22.589718+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000921","title":"Long read whole genome sequencing data from brain postmortem tissue","description":"Chart genetic variation in the human brain in healthy controls and Parkinson’s disease (PD) patients.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-11T10:36:36.705923+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000922","title":"Extracellular vesicles from TGF-β-activated cancer-associated fibroblasts remodel the tumor microenvironment through EV surface-associated proteins. ","description":"In this study, we explored the function of extracellular vesicles (EVs) derived from non-activated cancer-associated fibroblasts (CAFs) and TGF-β-activated CAFs. We tested these two types of EVs on other cell types in the tumor environment, including cancer cells, CD8+ T cells, and CAFs. We further explored the protein cargo in EVs altered by TGF-β treatment using quantitative proteomics, and selected several highly upregulated proteins for further analysis. We found that the majority of these proteins were presented on the EV surface, and they regulated the target cells in an EV-cell contact dependent manner. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-20T16:27:42.974308+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000923","title":"Genome-wide analyses of cell-free DNA for therapeutic monitoring of patients with pancreatic cancer","description":"Determining response to therapy for patients with pancreatic cancer can be challenging.  We evaluated methods for assessing therapeutic response using cell-free DNA (cfDNA) in plasma samples from 40 patients with metastatic pancreatic cancer as part of the CheckPAC trial (NCT02866383).  Patients were evaluated before and after initiation of therapy using tumor-informed plasma whole-genome sequencing (WGMAF), and genome-wide cfDNA fragmentation profiles and repeat landscapes (ARTEMIS-DELFI).  Of those assessed with WGMAF, molecular responders had a median overall survival (OS) of 319 days compared to 126 days for non-responders (HR=0.29, 95% CI=0.11–0.79, p=0.011).  For ARTEMIS-DELFI, patients with low scores after therapy initiation had a longer median OS than patients with high scores (233 days versus 172 days, HR=0.12, 95% CI=0.046-0.31, p<0.0001).  We validated ARTEMIS-DELFI in a separate cohort of 40 patients with pancreatic cancer who were part of the PACTO trial (NCT02767557).  These analyses suggest that non-invasive mutation and fragmentation-based cfDNA approaches can identify therapeutic response of individuals with pancreatic cancer.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-01T16:38:30.444202+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000924","title":"Mechanism of Decitabine response in MDS/AML patients","description":"Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with complex or monosomy karyotype show high prevalence of TP53 mutations (TP53m), poor response to induction chemotherapy and adverse outcome. These diseases may respond to decitabine but the mechanisms are presently unclear. This study investigates MDS/AML patients who were treated with decitabine for 10 days in a Phase II clinical trial. Serial samples  were collected from patients before and at completion of decitabine treatment, morphologic remission and relapse. The samples were interrogated using single-cell transcriptomics to investigate potential interactions between leukemic and immune populations.\"","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-23T02:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000925","title":"Acute lymphoblastic leukemia in children produces endogenous T-cells targeting tumor associated antigens and neoantigens in peripheral blood ","description":"In this study we investigated the presence of endogenous T-cells recognizing private tumor-associated antigens and predicted neoantigens. To this end, HLA-I and HLA-II restricted tumor associated antigens (TAAs) and neoantigens were respectively identified and predicted from matched tumor and germline (PBMCs) in three acute lymphoblastic leukemia patients. Circulating T-cells targeting both Mass spectrometry (MS)-identified TAAs and predicted neoantigens were identified in virtually all pediatric BCP-ALL patients, extending up to two years on remission.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-01T12:18:06.842086+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000926","title":"Investigating immunopathological signatures associated with COVID-19 severity post Omicron","description":"The aim of this study was to investigate the type and duration of protective immunity alongside immunopathological signatures associated with COVID-19 severity.\r\nRNA sequencing was performed using the Illumina Stranded mRNA Prep Ligation kit to investigate the protein coding transcriptome of PBMC cells.\r\nT cell receptor (TCR) repertoire profiling was performed with the TakaraBio SMART-Seq Human TCR (with UMIs) on PBMC cells to investigate the depth and persistence of SARS-CoV-2 targeting TCRs.\r\nThe cohort (n=20) consisted of 10 non-hospitalised and 10 Hospitalised individuals with samples analysed 3 months post positive SARS-CoV-2 PCR. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-07T16:27:10.557169+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000927","title":"Clonal Evolution and Transcriptional Plasticity Shape Metastatic Dissemination Routes in Prostate Cancer","description":"This study provides comprehensive insights into the genetic and transcriptomic landscape of prostate cancer, highlighting significant clonal heterogeneity, transcriptional plasticity, and metastatic spread patterns. We examined the clonal evolution and metastatic dissemination of prostate cancer by integrating single-nuclei RNA sequencing (snRNA-seq) and low-pass whole-genome sequencing (WGS) data from 43 spatially distinct tumour samples in five patients with locally advanced disease. By reconstructing the evolutionary trajectories of each tumour, we identified distinct patterns of tumour evolution, including both monophyletic and polyphyletic metastatic dissemination, as well as ongoing primary tumour clonal evolution after metastatic spread. We observed converging changes leading to metastatic potential, such as androgen receptor independence and increased activity in the estrogen, WNT, and JAK/STAT pathways in identified seeding areas. These findings enhance our understanding of the disease's progression and may inform future therapeutic strategies.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-22T14:37:09.51073+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000928","title":"Raw RNA sequencing of hepatoblastoma PDX cell line HB-303-LEF","description":"Raw RNA sequencing of hepatoblastoma PDX cell line HB-303-LEF","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-16T11:09:56.03503+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000929","title":"Mutational Profile in Newly Diagnosed Diffuse Large B-Cell Lymphoma: GAINED Study","description":"The GAINED study (NCT01659099) is a randomized phase 3 trial comparing obinutuzumab (G) to rituximab (R) in combination with ACVBP or CHOP14 induction, followed by PET-guided consolidation. This post-hoc analysis focuses on primary mediastinal B-cell lymphoma (PMBL) patients, confirmed through expert pathological review and characterized using gene-expression profiling (GEP) and Next-Generation Sequencing (NGS)","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[33211799],"external_links":null,"is_released":true,"released_date":"2025-04-01T09:15:16.147237+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000930","title":"A human induced pluripotent stem cell toolbox for studying sex chromosome effects-Whole exome seq","description":"To generate autosomaly isogenic hiPSCs with various chromosome complement, we use Klinefelter syndrome patient skin fibroblasts. These cells harbour XXY sex chromosomes, which can be lost during the reprogramming event and generate cells which are autosomaly identical to each other but differ in sex chromosome complement. We use state of the art reprogramming methods to generate panels of isogenic XXY, XX and XY iPSCs from XXY patient fibroblasts. We have performed Whole exome sequencing on Klinefelter syndrome patient's skin fibroblasts in order to check if two X chromosomes are identical and to see if we can distinguish which X chromosome is more likely to be lost during the reprogramming event in XY cell lines. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-29T12:20:04.279339+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000931","title":"A human induced pluripotent stem cell toolbox for studying sex chromosome effects -transcriptional landscape","description":"We use state of the art reprogramming methods to generate panels of isogenic XXY, XX and XY iPSCs from XXY patient fibroblasts. We use CRISPR/Cas9 system to evict Y chromosome from XY cells and generate XO iPSCs. The generation and characterisation of panels of isogenic XXY, XX, XY and XO iPSCs will provide a foundational toolkit to study sex differences in vitro. As iPSCs can be differentiated into any somatic cell type, we can apply the model to any human disease. We have generated bulk RNA-Seq from 12 autosomally isogenic hiPSCs to investigate transcriptional landscape and any differences in those cells in pluripotent state.\r\n\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-10T16:59:33.182499+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000932","title":"High-grade B-cell lymphoma, not otherwise specified: an LLMPP study","description":"Molecular characterization of high-grade B-cell lymphoma, not otherwise specified (HGBCL-NOS), is hindered by its rarity, evolving definition, and poor diagnostic reproducibility. To address this challenge, we analyzed 92 HGBCL-NOS tumors collected across Lymphoma/Leukemia Molecular Profiling Project sites. These tumors were profiled using whole-genome sequencing (WGS) or whole-exome sequencing (WES) to identify somatic mutations, WGS or low-pass WGS to detect copy number alterations, targeted capture sequencing to assess MYC and BCL2 structural variants, and RNA sequencing. The genetic features of HGBCL-NOS were compared to those of diffuse large B-cell lymphoma (DLBCL-NOS) and EBV-negative adult Burkitt lymphoma (BL). DLBCL-NOS tumors underwent targeted capture sequencing using a panel of 125 genes recurrently mutated in aggressive B-cell lymphomas. BL biopsies were drawn from the Burkitt Lymphoma Genome Sequencing Project and had available WGS (dbGaP Study Accession: phs000527.v18.p6).","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[40674706,40162293],"external_links":null,"is_released":true,"released_date":"2025-07-25T11:07:52.033343+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000933","title":"Cholesterol homeostasis and lipid raft dynamics at the basis of tumor-induced immune dysfunction in chronic lymphocytic leukemia","description":"Autologous T-cell therapies show limited efficacy in chronic lymphocytic leukemia (CLL), where acquired immune dysfunction\r\nprevails. In CLL, disturbed mitochondrial metabolism has been linked to defective T-cell activation and proliferation. Recent\r\nresearch suggests that lipid metabolism regulates mitochondrial function and differentiation in T cells, yet its role in CLL remains\r\nunexplored. This comprehensive study compares T-cell lipid metabolism in CLL patients and healthy donors, revealing critical\r\ndependence on exogenous cholesterol for human T-cell expansion following TCR-mediated activation. Using multi-omics and\r\nfunctional assays, we found that T cells present in viably frozen samples of patients with CLL (CLL T cells) showed impaired\r\nadaptation to cholesterol deprivation and inadequate upregulation of key lipid metabolism transcription factors. CLL T cells\r\nexhibited altered lipid storage, with increased triacylglycerols and decreased cholesterol, and inefficient fatty acid oxidation (FAO).\r\nFunctional consequences of reduced FAO in T cells were studied using samples from patients with inherent FAO disorders. Reduced\r\nFAO was associated with lower T-cell activation but did not affect proliferation. This implicates low cholesterol levels as a primary\r\nfactor limiting T-cell proliferation in CLL. Consequently, CLL T cells displayed fewer and less clustered lipid rafts, potentially\r\nexplaining the impaired immune synapse formation observed in these patients. Our findings highlight significant disruptions in\r\nlipid metabolism as drivers of functional deficiencies in CLL T cells, underscoring the pivotal role of cholesterol in T-cell proliferation.\r\nThis study suggests that modulating cholesterol metabolism could enhance T-cell function in CLL, presenting novel\r\nimmunotherapeutic approaches to improve outcome in this challenging disease.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-03T16:59:16.575215+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000934","title":"Exome sequencing study of cells derived from QHJI14s04 human iPSC secondary cell stock","description":"Genomic abnormalities of cells used in regenerative medicine should be checked.\r\nThis study evaluates variants on coding sequences of cells derived from QHJI14s04 human iPSC secondary cell stock.\r\nHere we conducted whole exome sequence of three vials from the stock.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-07T18:58:19.246756+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000935","title":"Sequencing data of tumor tissue obtained from GANNET53 study patients","description":"The GANNET53 clinical trial evaulated novel treatment options for ovarian cancer patients with platinum-resistant relapse. Archival fresh-frozen paraffin embedded tissue was available from 131 of the 133 enrolled patients. NGS sequencing aimed at assessing the mutational spectrum of key ovarian cancer genes (with a focus on TP53), and their relevance for therapy resistance. From available FFPE samples, DNA was extracted and NGS sequenced using the SureSeq™ Ovarian Cancer Panel and the NGS Library Preparation kit covering all exons of 7 key ovarian cancer genes BRCA1, BRCA2,TP53, PTEN, ATM, ATR, NF1 for single nucleotide variants (SNV) and indels. Finally, sequence data from 118 individual FFPE tumor tissue samples were generated.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-07T15:12:41.122763+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000936","title":"Initial leukemic epigenomic state determines hypomethylating agent response","description":"Hypomethylating agents (HMAs) are a mainstay of therapy for myeloid cancers, but genetic biomarkers do not predict who will respond to treatment. Using a variety of single-cell sequencing approaches to define the epigenomic state of responder and nonresponder leukemic cells, we aim to demonstrate that leukemic stem cells (LSC) exist in at least two different epigenomic states: a hematopoietic stem cell (HSC)-or multipotent progenitor (MPP)-like state that is sensitive to HMAs, independent of genetic mutations, or a lymphoid-primed MPP (LMPP)-like nonresponder state. Additionally, we aim to demonstrate that hypomethylation and chromatin accessibility at ZNF143- and CTCF-binding sites result in activation of HOXB4, which defines the HSC/MPP-like state and HMA-sensitivity. Our study aims to provide evidence that the epigenomic state of the LSC is a major determinant of response to HMAs, and demonstrates that a routine clinical assay can identify patients who will respond.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-04T11:52:02.061753+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000937","title":"Single-cell/single-nucleus RNA-seq of Embryonal Tumor with Multilayered Rosettes (ETMR)","description":"Embryonal tumor with multilayered rosettes (ETMR) is a pediatric brain tumor with dismal prognosis. We analyzed eleven ETMR patient samples using single-cell transcriptomics. We reveal a spatially distinct cellular hierarchy that spans highly proliferative neural stem-like cells and more differentiated neuron-like cells. C19MC is predominantly expressed in stem-like cells and controls a transcriptional network governing stemness and lineage commitment. Systematic analysis of receptor-ligand interactions between malignant cell types reveals FGFR and NOTCH signaling as oncogenic pathways. Our study provides fundamental insights into ETMR pathobiology and a powerful rationale for more effective targeted therapies.\r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-14T10:54:54.996997+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000938","title":"Low T cell diversity is associated with poor outcome in bladder cancer - Single cell RNAseq and TCRseq data","description":"T cells are crucial effector cells in the endogenous defense against cancer, yet the clinical impact of their quantity, diversity, and dynamics remains underexplored. In this study we performed single cell RNAseq paired with single cell TCR-seq on tumor and blood samples from 4 patients (n samples = 8). The goal was to investigate T cell subtypes of expanded and non-expanded T cell clones in blood and in tumors.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-04T09:16:10.985803+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000939","title":"Low T cell diversity is associated with poor outcome in bladder cancer - Total RNAseq data","description":"T cells are crucial effector cells in the endogenous defense against cancer, yet the clinical impact of their quantity, diversity, and dynamics remains underexplored. In this study we performed total RNAseq on blood samples from 8 patients with muscle invasive bladder cancer. The goal was to compare blood T cell subtype composition between patients with low and high TCR diversity.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-04T09:16:08.15238+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000940","title":"Low T cell diversity is associated with poor outcome in bladder cancer - Bulk TCRseq data","description":"T cells are crucial effector cells in the endogenous defense against cancer, yet the clinical impact of their quantity, diversity, and dynamics remains underexplored. In this study we performed bulk TCRseq on tumor and serial blood samples from patients with muscle invasive (n patients = 119) or non-muscle invasive bladder cancer (n patients = 30). The goal was to investigate the clinical relevance of the blood and tumor TCR repertoire in patients with bladder cancer.  ","abstract":null,"study_type":"Pooled Clone Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-04T09:16:13.143959+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000941","title":"mRNA-seq of paired Follicular Lymphoma (FL) patient samples before and after high-grade transformation to DLBCL (FL vs. tFL) from FFPE tissues","description":"The aim of this study was to analyze transcriptional changes in paired samples of follicular lymphoma (FL) and its histological transformation (tFL). Transformation of FL is an adverse event in the course of the disease and is associated with poor outcome. Several genetic aberrations have been linked to tFL pathogenesis, but gene expression changes and microenvironmental interactions have not been well characterized. We performed RNA profiling of FL and paired tFL samples transformed to DLBCL (n=11 pairs). For RNA profiling, we utilized libraries prepared using RNA isolated from archival FFPE tissues. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-15T13:46:59.439784+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000942","title":"miRNA-seq of paired Follicular Lymphoma (FL) patient samples before and after high-grade transformation to DLBCL (FL vs. tFL) from FFPE tissues","description":"The aim of this study was to analyze transcriptional changes in paired samples of follicular lymphoma (FL) and its histological transformation (tFL). Transformation of FL is an adverse event in the course of the disease and is associated with poor outcome. Several genetic aberrations have been linked to tFL pathogenesis, but gene expression changes and microenvironmental interactions have not been well characterized. We performed miRNA profiling of FL and paired tFL samples transformed to DLBCL (n=10 pairs). For miRNA profiling, we utilized libraries prepared using RNA isolated from archival FFPE tissues. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-20T14:58:13.415338+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000943","title":"Phenotypic characterization and prognostic impact of CD103+ tissue-resident memory T cells in diffuse large B cell lymphoma","description":"Tissue-resident memory T (TRM) cells are a population of memory T cells that stably occupy tissues and play a key role in immunosurveillance, having been linked to favorable survival outcomes in various solid tumors. While TRM cells have been identified in lymph nodes, their phenotype and prognostic significance in B-cell non-Hodgkin lymphoma (B-NHL), including diffuse large B-cell lymphoma (DLBCL), remains poorly characterized.  The frequency of CD103 expressing T cells in patient samples with DLCBL was quantified by immunofluorescence (IF) staining of tissue biopsies (n=306) and flow cytometry (n=252) of cell disaggregates, and linked with clinical outcome. The phenotype of TRM cells was characterized by spectral flow cytometry (n=10 DLBCL and 2 reactive lymph node (rLN) samples) and single-cell RNA sequencing (scRNAseq) (n=12 aggressive B cell lymphomas and 4 rLN samples). An additional 51 samples from an external dataset were included to verify the single cell transcriptome findings. The flow cytometry and scRNAseq findings in DLBCL were extrapolated to additional B-NHL entities. Through analysis of these datasets we were able to characterize CD103+ TRM-like cells in DLBCL and other B-NHL entities and identified them to represent a prognostically favorable population with an activated/cytotoxic T cell phenotype.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-10T16:20:18.922673+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000944","title":"Homologous recombination status determination through mutational and copy number profiling of ovarian cancer biopsies from the MITO16A/MaNGO-OV2 study","description":"We evaluated copy number signatures and BRCA mutation status on a cohort of 469 samples from the MITO16A/MaNGO-OV2 study.  We extracted copy number signatures as described previously (Steele et al., Nature, 2022) and along with BRCA status the sequencing data were used to train a machine learning model for the determination of homologous recombination (HR) status (either deficient or proficient) for each sample","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000945","title":"Homologous recombination status determination through mutational and copy number profiling of ovarian cancer biopsies from the PAOLA-1 study","description":"We evaluated copy number signatures and BRCA mutation status on a cohort of 469 samples from the PAOLA-1 study.  We extracted copy number signatures as described previously (Steele et al., Nature, 2022) and along with BRCA status the sequencing data were used to train a machine learning model for the determination of homologous recombination (HR) status (either deficient or proficient) for each sample","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000946","title":"Aberrant splicing of MBD1 reshapes the epigenome to drive convergent myeloerythroid defects in MDS","description":"Splicing defects are a characteristic feature of myelodysplastic syndromes (MDS) and typically associate with specific recurrent splicing factor mutations. However, a subset of transcripts exhibit abnormal splicing regardless of mutational background, occurring even in the absence of splicing-related mutations. We identified a long isoform of Methyl-CpG-Binding Domain 1 (MBD1) as the product of one such mutation-independent splicing event. To understand whether altered MBD1 splicing contributes to hematopoietic dysfunction, we overexpressed the long (MBD1-L) and short (MBD1-S) isoforms of MBD1 in cord blood CD34+ cells. We found that the MBD1-L isoform specifically impaired reconstitution capacity in vivo, particularly in the erythroid lineage, and produced a unique pattern of transcriptomic repression on RNA-seq compared to MBD1-S. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-05T10:26:21.949633+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000947","title":"Linked-Read Whole Genome Sequencing Profiles Structural Variant Landscape of Gliomas with Barcode-Level Evidence","description":"Structural variants (SVs) play essential roles in glioma oncogenesis and offer prognostic insights, yet the SV landscape of gliomas has not been completely characterized due to previous technological limitations. To comprehensively profile the SV landscape of gliomas, we performed linked-read whole genome sequencing (LR-WGS) on 31 tumour samples from 20 glioma patients. Using barcode-level evidence, we validated known SVs and identified the presence of extrachromosomal DNA containing the EGFR sequence, which correlates with elevated EGFR expression. Additionally, we uncovered rare SVs affecting genes typically mutated by single nucleotide variants (SNVs), including those in the SWI/SNF chromatin remodeling complex. Our analysis also reveals selective chromosomal vulnerabilities to SVs, highlighting certain chromosomes as hotspots for SV accumulation. Collectively, our results demonstrate the utility of LR-WGS in accurately detecting SVs and thoroughly profiling SV landscapes using barcode-level evidence. The insights gained into the synergistic effects of SNVs and SVs on oncogenes further underscore the importance of integrating SV analysis when examining mutations in gliomas.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-12T11:00:32.910844+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000948","title":"Dietary convergence induces individual responses in faecal microbiome composition","description":"This dietary intervention employed an ABA design where participants maintained their habitual diet during baseline and washout periods, while restricting intake to only oats, whole milk, and water during the intervention phase. The study deliberately imposed this severe dietary shift to maximize observable effects on gut microbiome composition and function.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000949","title":"Cohort A tumor exome sequencing","description":"Cohort A includes glioma tumors of varied grading and pathology from male and female individuals.  Tumor DNA was isolated from fresh frozen tissue.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-07T09:41:59.490755+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000950","title":"Cohort A RNA sequencing","description":"Cohort A includes glioma tumors of varied grading and pathology from male and female individuals. RNA was isolated from fresh frozen glioma tissue of each sample tumor block from Cohort A.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-07T09:41:59.490755+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000951","title":"Cohort B germline exome sequencing","description":"Cohort B includes IDH-wild type, EGFR amplified, surgically derived glioblastoma tissue samples from male and female individuals.  Germline DNA was isolated from whole blood.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-07T09:41:59.490755+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000952","title":"Cohort A germline exome sequencing","description":"Cohort A includes glioma tumors of varied grading and pathology from male and female individuals. Germline DNA was isolated from whole blood.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-07T09:41:59.490755+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000953","title":"Cohort B RNA sequencing","description":"Cohort B includes IDH-wild type, EGFR amplified, surgically derived glioblastoma tissue samples from male and female individuals. RNA was isolated from FFPE glioma tissue of each sample from Cohort B.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-07T09:41:59.490755+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000954","title":"Cohort A spatial transcriptomics sequencing","description":"Cohort A includes glioma tumors of varied grading and pathology from male and female individuals. Fresh frozen glioma tissues for each sample in cohort A were analyzed with the 10X Genomics Visium Spatial Gene Expression protocol. Processed data is available on the NCBI Gene Expression Omnibus database with accession GSE242352.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-07T09:41:59.490755+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000955","title":"Cohort B tumor exome sequencing","description":"Cohort B includes IDH-wild type, EGFR amplified, surgically derived glioblastoma tissue samples from male and female individuals.  Tumor DNA was isolated from FFPE tissue. Both tumor and germline DNA are present for each sample in the overall dataset.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-07T09:41:59.490755+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000956","title":"Cohort B spatial transcriptomics sequencing","description":"Cohort B includes IDH-wild type, EGFR amplified, surgically derived glioblastoma tissue samples from male and female individuals. FFPE tissues for each sample in cohort B were analyzed with the 10X Genomics Visium CytAssist protocol. Processed data is available on the NCBI Gene Expression Omnibus database with accession GSE242352.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-07T09:41:59.490755+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000957","title":"Efficacy of asciminib in acute lymphoblastic leukaemia (ALL) patient derived NUP214::ABL1 xenografts.","description":"Study to assess the activity of the STAMP inhibitor asciminib against NUP214::ABL1 acute lymphoblastic leukaemia (ALL). mRNA-sequencing was performed on ALL patient samples to identify the NUP214::ABL1 gene fusion, determine the genomic breakpoint of the fusion and identify co-occurring mutations. Patient-derived xenografts (PDX) were established from three ALL patients (one T-cell ALL and two B-cell ALL) with NUP214::ABL1 disease and used to assess asciminib activity in vivo.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-20T14:55:32.278066+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000958","title":"Transcriptomics profile of stem cell-derived islets treated with purification protocol vs control","description":"Differentiation protocol for generating stem cell-derived islet cells can result in the generation of unwanted cells that may affect islet growth and survivability in vivo, such as exocrine cells. The goal of this experiment is to determine how gradient-based purification protocol as detailed by Rajaei et al., 2025 (Science Translational Medicine, approved, pending PMID) affect the composition of stem cell-derived islets (stem cell used: HUES8)\r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000959","title":"Comparison of the treated celiac disease microbiome to that of controls","description":"Coeliac disease (CeD) is an immune-mediated disorder primarily affecting the small intestine, characterised by an inflammatory immune reaction to dietary gluten. CeD onset results from a multifaceted interplay of genetic and environmental factors. While recent data show that alterations in gut microbiome composition could play an important role, many current studies are constrained by small sample sizes and limited resolution. To address these limitations, we analysed faecal gut microbiota from two Dutch cohorts, CeDNN (128 treated CeD patients (tCeD), 106 controls) and the Lifelines Dutch Microbiome Project (24 self-reported tCeD, 654 controls), using shotgun metagenomic sequencing. Self-reported IBS (570 cases, 1710 controls) and IBD (93 cases, 465 controls) were used as comparative conditions of the gastrointestinal tract. Interindividual variation within the case and control groups was calculated at whole microbiome and strain level. Finally, species-specific gene repertoires were analysed in tCeD patients and controls. Within-individual microbiome diversity was decreased in patients with self-reported IBS and IBD but not in tCeD patients. Each condition displayed a unique microbial pattern and, in addition to confirming previously reported microbiome associations, we identify an increase in the levels of Clostridium sp. CAG:253, Roseburia hominis, and Eggerthella lenta, amongst others. We further show that the observed changes can partially be explained by gluten-free diet adherence. We also observe increased interindividual variation of gut microbiome composition among tCeD patients and a higher bacterial mutation frequency in tCeD that contributes to higher interindividual variation at strain level. In addition, the immotile European subspecies of Eubacterium rectale, which has a distinct carbohydrate metabolism potential, was nearly absent in tCeD patients. Our study sheds light on the complex interplay between the gut microbiome and CeD, revealing increased interindividual variation and strain-level variation in tCeD patients. These findings expand our understanding of the microbiome’s role in intestinal health and disease.\r\n\r\nNote that some of the data in this study belong to the Lifelines cohort. Access to this dataset can be requested via the page of the EGA data access committee EGAC00001001996. The phenotype data can be requested, for a fee, by filling the application form at https://www.lifelines.nl/researcher/how-to-apply/apply-here. ","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-04T14:19:41.451414+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000960","title":"Chlamydia trachomatis exploits sphingolipid metabolic pathways during infection of phagocytes","description":"This study looks at the response of M2 macrophages stimulated with GM-CSF and IL4 for 7 days and 2 days respectively to C. trachomatis infection on an Illumina platform.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-15T13:14:15.355948+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000961","title":"Indonesian Microbiome Ecology and Evolution","description":"This study investigates patterns of human gut microbiome variation across Indonesia. We performed metagenome-assembled genome (MAG) assembly and employed genome-resolved methods to quantify and characterise microbial abundance within and across sampled communities, that span hunter-gatherer, agricultural and urban contexts. Paired with lifestyle, diet and biometric metadata, this study seeks to disentangle the drivers of microbiome variation across communities, lifestyle and geography.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-04-11T13:45:59.679171+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000962","title":"ACUITI","description":"This study assessed the feasibility and performance of a tumor-informed circulating tumor DNA (ctDNA) assay in patients with metastatic HR+/HER2- breast cancer receiving endocrine therapy and CDK4/6 inhibitors.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-19T17:33:09.643764+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000963","title":"Tissue-specificity and co-expression analyses identify human long non-coding RNAs related to inherited retinal disease genes ","description":"The role of long non-coding RNAs (lncRNAs) in biological and pathological processes is still poorly understood. In this study, we aimed to identify lncRNAs that potentially contribute to retinal biology and Inherited Retinal Disease (IRD) by using two complementary strategies, tissue-specificity and location in topologically associating domains (TADs) containing IRD genes on one hand, and co-expression analyses on the other, applied to human retinal omics datasets. This combined approach resulted in the selection of 11 Retina Enriched IRD-gene Related (REIR) lncRNAs, one of which is novel. In-depth in silico and experimental characterization of REIRs identified novel REIR isoforms and confirmed retina-predominant (often photoreceptor-specific) expression as well as predicted functional association with visual function. Long-read direct cDNA sequencing (ONT) of three post-mortem human retina samples was used to delineate the novel REIR isoforms. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-10T12:43:31.958289+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000964","title":"10X snRNA-seq data from human FCDII postoperative brain tissues with mTOR pathway mutations","description":"Focal cortical dysplasia type II (FCDII) is linked to mTOR pathway mutations and drug-resistant epilepsy. Using 10X snRNA-seq on postoperative FCDII brain tissues, we characterized transcriptional alterations across cell types, revealing mTOR-related dysregulation. These findings provide insights into FCDII pathology and potential therapeutic target","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-18T16:24:12.027836+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000965","title":"Transcriptome changes in circulating immune cells of critical COVID-19 patients predict  a specific metabolic and epigenetic imprint","description":"The progression to severe COVID-19 arises predominantly from a dysregulated host immune response, although the underlying regulatory mechanisms still remain partially elusive. This limits a prompt prediction of disease progression and restrains our understanding of “long COVID”. Here, we analyzed the transcriptomes of peripheral blood mononuclear cells collected from COVID-19 patients experiencing different degrees of the disease and control patients. In critical COVID-19 patients, we found an altered regulatory network involving microRNAs, long non-coding RNAs, and coding genes that control mRNA translation-related genes, epigenetics, and metabolism. We also observed an upregulation of tRNA aminoacylation genes and increased expression of coding genes enriched for the cognate amino acids. Collectively, our findings indicate a broad perturbation of the gene expression landscape that characterizes the aberrant host immune response in critical COVID-19 patients and is potentially coordinated by alterations in microRNA expression and tRNA metabolism.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-18T12:13:10.124818+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000966","title":"Whole Exome Sequencing of Human Gastro-esophageal Cancer PDXs","description":"The current study investigates biomarkers of response to anti-EGFR therapies in gastro-esophageal cancer. Whole exome sequencing was performed on 26 tumors to explore potential factors influencing treatment outcomes. As part of the analysis, somatic mutations in EGFR, ERBB2, and key downstream signaling genes (KRAS and PIK3CA) were examined to exclude the presence of known mutations conferring sensitivity/resistance. The study aims to contribute to the identification of patients who may benefit from lower-toxicity regimens, improving treatment personalization and minimizing adverse effects.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-28T09:49:32.981538+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000967","title":"Single-cell tracking reveals tumor-reactive T cell plasticity during melanoma TIL therapy","description":"Using 10x genomics 5' Single Cell Immune Profiling kit for single-cell RNA and TCR sequencing, we tracked the transcriptional alterations and fate decisions of tumor-reactive T cells through longitudinal sample obtained from patients undergo-ing TIL therapy. We performed single-cell RNA and single-cell TCR sequencing (scRNA-seq and scTCR-seq) of CD45+ CD3+ tumor-infiltrating lymphocytes from the baseline tumor (pre-ACT), during and after TIL expansion protocol (intermediate product and TIL product, respectively), as well as after cell transfer in blood (PBMC 7dpt) or from metastatic lesions (post-ACT). Samples were derived from patients enrolled in a phase I clinical trial (NCT04165967) that inves-tigated ACT-TIL therapy in combination with nivolumab therapy for metastatic melanoma. Additionally, we established a tumor reactivity assay by co-culturing TIL products with autologous single-cell suspensions of tumor material or short cultured primary melanoma cell lines derived from the tumor material. Reactive T cells were identified by IFNɣ and TNF⍺ expression and sorted to sequence TCRβ genes.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-27T10:12:42.627032+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000968","title":"The DIRECT study: A roadmap for ctDNA-based risk prediction, molecular profiling and MRD detection in Diffuse Large B Cell Lymphoma","description":"DIRECT was a prospective, multisite study assessing the feasibility and utility of circulating tumor DNA (ctDNA) in 188 patients with aggressive B-cell non-Hodgkin lymphoma using capture panel sequencing and an open-source computational pipeline. The aims of the study were 1)baseline risk stratification, 2)genetic profiling and 3)ultrasensitive minimal residual disease (MRD) assessment. This study highlighted the considerable potential, but also the caveats and limitations, of ctDNA technology when applied to aggressive B-cell lymphoma.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-02T14:47:28.750147+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000969","title":"Reproducible gut microbial signatures in bipolar and schizophrenia spectrum disorders: A metagenome-wide study","description":"This is a case-control study in which differences in the gut microbiome of patients with bipolar disorder and schizophrenia spectrum disorders were assessed. The study contains the samples in this dataset, except for G002, G025, G041, G093, G106, G107, G120 and G123. These samples were not yet available at the time the study was performed. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[39032544],"external_links":null,"is_released":true,"released_date":"2025-12-24T12:10:37.11536+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000970","title":"SCANDARE TNBC","description":"Prospective biobanking study in breast patients aiming at better understand the link between the molecular alterations of the tumor itself, its microenvironment and immune response.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-01T12:21:21.844728+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000971","title":"Confronting historical legacies of biological anthropology in South Africa—Restitution, redress and community-centered science: The Sutherland Nine","description":"We describe a process of restitution of nine unethically acquired human skeletons to their families, together with attempts at redress. Between 1925–1927 C.E., the skeletonised remains of nine San or Khoekhoe people, eight of them known-in-life, were removed from their graves on the farm Kruisrivier, near Sutherland in the Northern Cape Province of South Africa. They were donated to the Anatomy Department at the University of Cape Town. This was done without the knowledge or permission of their families. The donor was a medical student who removed the remains from the labourers’ cemetery on his family farm. Nearly 100 years later, the remains are being returned to their community, accompanied by a range of community-driven interdisciplinary historical, archaeological and analytical (osteobiographic, craniofacial, ancient DNA, stable isotope) studies to document, as far as possible, their lives and deaths. The restitution process began by contacting families living in the same area with the same surnames as the deceased. The restitution and redress process prioritises the descendant families’ memories, wishes and desire to understand the situation, and learn more about their ancestors. The descendant families have described the process as helping them to reconnect with their ancestors. A richer appreciation of their ancestors’ lives, gained in part from scientific analyses, culminating with reburial, is hoped to aid the descendant families and wider community in [re-]connecting with their heritage and culture, and contribute to restorative justice, reconciliation and healing while confronting a traumatic historical moment. While these nine individuals were exhumed as specimens, they will be reburied as people.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[37224187],"external_links":null,"is_released":true,"released_date":"2026-02-19T12:45:29.085732+01:00","is_deprecated":false},
{"accession_id":"EGAS50000000972","title":" Ontario Institute for Cancer Research; Biliary Tract Cancer","description":"Next Generation Sequencing data from Biliary Tract cancers","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-16T15:07:14.001492+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000973","title":"Multi-omics bulk and single-cell profiling of epithelioid sarcoma","description":"Epithelioid sarcoma (EpS) is an aggressive sarcoma, characterized by the loss of SMARCB1 expression. EpS is traditionally classified as distal or proximal according to clinicopathological features, but its molecular characteristics remain largely unknown. To establish an EpS molecular classification and uncover determinants of inter- and intra-patient heterogeneity in EpS, we used multi-omics profiling and integrated the genomic, transcriptional and methylome landscapes with single-cell RNA sequencing on fresh samples as well as spatial transcriptomics. We identified two molecular subtypes of EpS: “distal-like” and “proximal-like”, which were distinct from the histological subtypes. Distal-like tumors include all morphological distal subtypes and a subset of proximal and hybrid EpS. They express a specific molecular single-cell derived epithelial-to-mesenchymal transition signature, which associates with improved patient survival and includes Desmoglein 2 (DSG2), which we identify as a potential routine immunohistochemical biomarker to improve diagnosis. Distal-like EpS also display increased peri-tumoral CD8+ T cell infiltrates and specific tumor-immune cell interactions. Conversely, proximal-like EpS harbor a higher inter-tumoral molecular heterogeneity with some cases resembling other SMARCB1-deficient tumors by DNA methylation profiling, and increased intra-tumoral pro-tumoral macrophage infiltrates. Our study introduces a novel molecular classification of EpS with prognostic value, associated diagnostic biomarkers and distinct tumor immune microenvironments, which extends beyond traditional clinicopathological classification. This paves the way for precision medicine-based therapeutic strategies for patients with EpS.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-28T11:08:51.051835+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000974","title":"Final results and ctDNA analyses from the randomized phase 3 IMpassion031 trial evaluating peri-operative atezolizumab for early-stage triple-negative breast cancer ","description":"In IMpassion031, adding atezolizumab to neoadjuvant chemotherapy significantly improved pathologic complete response (pCR) rate (primary endpoint) for stage II/III triple-negative breast cancer (TNBC). Patients with stage II/III TNBC were randomized 1:1 to neoadjuvant chemotherapy plus peri-operative atezolizumab or pre-operative placebo. Descriptive secondary endpoints included event-free, disease-free, and overall survival. Long-term outcomes favored the atezolizumab group (event-free survival HR 0.76, 95% CI: 0.47–1.21). Among patients without pCR, 14/70 (20%) atezolizumab-treated and 33/99 (33%) placebo-treated patients received additional adjuvant therapy, frequently capecitabine. In exploratory analyses, pCR was prognostic for long-term outcome. Patients with baseline ctDNA-negative status (6%) had excellent long-term outcomes. Most patients (87%) had cleared ctDNA at surgery. ctDNA-positive status at surgery identified a subset of non-pCR patients with poorest prognosis. Long-term safety was consistent with primary results. Adding atezolizumab to chemotherapy for stage II/III TNBC is associated with more favorable long-term outcomes. ctDNA dynamics provide prognostic value beyond pCR. ClinicalTrials.gov identifier: NCT03197935","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-19T17:17:15.126622+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000975","title":"Stress Granules Underlie Acute Myeloid Leukemia Stem Cell Survival and Stress Adaptation","description":"The development of novel leukemic stem cell (LSC)-targeted therapeutics is an urgent goal towards reducing the high, LSC-driven relapse rates in acute myeloid leukemia (AML). Towards elucidating key LSC dependencies we mined our published CRISPR serial transplant dropout screen to uncover an enrichment of stress granule (SG) proteins as crucial for LSC-mediated AML growth. SGs are dynamic stress-adaptive ribonucleoprotein complexes, which may form a cancer protective mechanism, but their role in LSCs is unknown. To address this, we focused on G3BP1, a core SG nucleation factor. In a series of G3BP1 knockdown and small molecule SG inhibition assays, we demonstrate that SG impaired cells showed increased apoptosis, reduced AML competition in vitro and importantly, in vivo, LSCs with G3BP1 knocked down were significantly compromised. Multi-omics analysis highlighted numerous SG-driven mechanisms of cancer cell stress resistance and/or stem cell regulatory processes. In particular, we uncover an SG-driven AML cell survival mechanism as enacted through the coordination of the RNA helicase UPF1 with G3BP1 to allow for specific degradation of pro-apoptotic mRNA containing highly structured 3’ UTRs.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000976","title":"Sensitive neoantigen discovery by real-time mutanome-guided immunopeptidomics - WES","description":"Targeting cancer-specific HLA-peptide complexes is a promising immunotherapy approach, with mutated neoantigens offering high value for their immunogenicity and cancer-specificity. Selecting immunogenic targets requires personalized prioritization of cancer-specific immunopeptides. Mass spectrometry (MS)-based immunopeptidomics supports this process by directly identifying cancer-specific antigens and informing global presentation patterns to refine immunogenicity predictions. Clinical pipelines, however, must balance global depth and target sensitivity compounded by low input samples and time constraints. Here, we present NeoDiscMS, an extension of the NeoDisc pipeline, enabling personalized immunopeptidomics data acquisition. By leveraging real-time NGS-guided spectral acquisitions, NeoDiscMS maximizing sensitivity with minimal loss of global depth. NeoDiscMS improves TAA-derived peptide detection up to 20% and enhances neoantigen identification confidence compared to the clinical gold standard method. Designed for effectiveness and ease of use, it requires minimal effort for implementation. NeoDiscMS advances personalization in clinical antigen discovery by enabling more sensitive neoantigen detection while seamlessly integrating into existing workflows.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-20T15:55:09.67772+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000977","title":"Sensitive neoantigen discovery by real-time mutanome-guided immunopeptidomics - RNAseq","description":"Targeting cancer-specific HLA-peptide complexes is a promising immunotherapy approach, with mutated neoantigens offering high value for their immunogenicity and cancer-specificity. Selecting immunogenic targets requires personalized prioritization of cancer-specific immunopeptides. Mass spectrometry (MS)-based immunopeptidomics supports this process by directly identifying cancer-specific antigens and informing global presentation patterns to refine immunogenicity predictions. Clinical pipelines, however, must balance global depth and target sensitivity compounded by low input samples and time constraints. Here, we present NeoDiscMS, an extension of the NeoDisc pipeline, enabling personalized immunopeptidomics data acquisition. By leveraging real-time NGS-guided spectral acquisitions, NeoDiscMS maximizing sensitivity with minimal loss of global depth. NeoDiscMS improves TAA-derived peptide detection up to 20% and enhances neoantigen identification confidence compared to the clinical gold standard method. Designed for effectiveness and ease of use, it requires minimal effort for implementation. NeoDiscMS advances personalization in clinical antigen discovery by enabling more sensitive neoantigen detection while seamlessly integrating into existing workflows.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-20T15:55:09.67772+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000978","title":"Dual inhibition of FLT3 and BCL-2 is effective in preclinical models of BCL11B-activated lineage ambiguous leukemia","description":"Aberrant activation of BCL11B (“BCL11B-a”) defines a subtype of lineage ambiguous leukemias with T-lymphoid and myeloid features, co-occurring activating FLT3 mutations, and a stem/progenitor immunophenotype and gene expression profile. As with other lineage ambiguous leukemias, optimal treatment is unclear and there are limited targeted therapeutic options. Here, we investigated the efficacy of BCL-2 and FLT3 inhibition with venetoclax and gilteritinib, respectively, in preclinical models of BCL11B-a leukemia. Despite variation in response to single agent therapies, the combination of venetoclax plus gilteritinib was highly effective in all models evaluated. BH3 profiling and single cell RNA-seq analysis suggests that resistance to venetoclax and/or gilteritinib monotherapies is due to the tumor-intrinsic activity of BCL-xL and/or MCL-1 prior to drug treatment. These data support clinical evaluation of venetoclax in combination with gilteritinib in BCL11B-a lineage ambiguous leukemias.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-22T13:31:03.694039+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000979","title":"Epigenetic profiling of acute myeloid leukemia","description":"In this study, we explored the epigenetic landscape of acute myeloid leukemia (AML) through multi-omic analysis. We analyzed a cohort of AML patients using bulk ATAC-seq (n=1563) and bulk RNA-seq (n=1398). Subsets of cases were also analyzed using DNA methylation EPIC array (n=424), ChIP-seq (for H3K27ac (n=234), H3K27me3 (n=217), SMC1 (n=209), CTCF (n=218), and RPB1 (n=220)), and single-cell RNA- and ATAC-seq (scRNA/ATAC-seq, n=36). AML cell lines (n=11) and normal bone marrow samples (n=25) were also anlayzed by bulk ATAC-seq. For scRNA/ATAC-seq, samples from remission bone marrow in 4 patients were analyzed as control. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000980","title":"Single cell transcriptome sequencing of the developing human embryonic meninges","description":"There are no effective medical therapies for meningiomas, partly due to our limited understanding of their cellular origin and composition For this purpose, we generated data to make a comprehensive reference single cell and spatial transcriptomic atlas of human fetal meninges. Samples of meninges from human embryos of post-conceptional week (PCW) 5.0-13.0 were dissected and subject to 10Xgenomics chromium single cell RNA sequencing with the purpose of identifying cell types and gene expression programs for normal meninges development, Furthermore, this dataset should help discover cells of origin for meningiomas.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-25T16:47:08.535507+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000981","title":"NOTCH1 orchestrates metabolic reprogramming to drive proliferation in chronic lymphocytic leukemia","description":"In Chronic lymphocytic leukemia (CLL), NOTCH1 mutations occur in ~10% of cases and are often associated with unmutated IGHV genes, defining a subgroup requiring earlier treatment. Using an engineered CLL cell line, we demonstrated that NOTCH1-mutated cells exhibit increased glucose uptake, oxidative metabolism, and proliferation, driven by enhanced mitochondrial mass and TFAM upregulation. Metabolic assays and stable isotope tracing revealed a greater dependency on glutamine and anabolic pathways in NOTCH1-mutated cells, promoting growth. These findings were validated in a cohort of NOTCH1-mutated patients, highlighting a molecular circuit linking BCR, NOTCH1, and mitochondrial metabolism. This study suggests that metabolic vulnerabilities in NOTCH1-mutated CLL could inform precision medicine strategies.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000982","title":"RISE-UP study: riboflavin supplementation in Crohn's disease","description":"Taxonomic classification of the fecal microbiota of Crohn's disease patients showing the shift in the gut bacterial community after riboflavin supplementation.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[31873717],"external_links":null,"is_released":true,"released_date":"2025-05-19T17:30:50.531748+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000983","title":"Comprehensive Multimodal Characterization and Subclassification of Young and Old Breast Cancer","description":"Multi-omics data comprising six data types — whole genome sequencing (WGS) (n=187), whole exome sequencing (WES) (n=274), DNA methylation (n=231), RNA sequencing (RNA-seq) (n=281), proteomics (n=249), and phosphoproteomics (n=248) — were generated from a total of 289 tissue samples. These samples were derived from 178 young breast cancer (YBC) patients and 111 older breast cancer (OBC) patients.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000984","title":"Tumor gene project","description":"The study focuses on human tumor susceptibility as well as somatic cancer genomics. We use high-throughput sequencing approaches to achieve a comprehensive molecular characterization of tumors. Our goal is to better understand their genesis and management opportunities.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-13T16:07:43.922335+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000985","title":"SPECTA RP-1759-AYA CNS cohort","description":"EORTC-SPECTA RP1759 study focuses on cancers in adolescent and young adult (AYA), age 12 to 29 years. This study explicitly recruited AYA patients and therefore collected empirical data to bridge the molecular gap between pediatric and adult oncology. The initial pilot study, activated in February 2019 across Europe, aimed to recruit 50 AYA patients (aged 12-29 years) with newly diagnosed or relapsed high-grade gliomas, and for which matching tumor and blood samples were collected.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-02T14:17:24.49682+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000986","title":"Detection of brain cancer using genome-wide cell-free DNA fragmentomes","description":"Diagnostic delays in patients with brain cancer are common and can impact patient outcome. Development of a blood-based assay for detection of brain cancers could accelerate brain cancer detection. In this study, we analyzed genome-wide cell-free (cfDNA) fragmentomes, including fragmentation profiles and repeat landscapes, from the plasma of individuals with (n=148) and without (n=357) brain cancer.  Machine learning analyses of cfDNA fragmentome features detected brain cancer across all grade gliomas (AUC=0.90, 95% CI: 0.87-0.93) and these results were validated in an independent prospectively collected cohort.  cfDNA fragmentome changes in patients with gliomas represented a combination of fragmentation profiles from glioma cells and altered white blood cell populations in the circulation.  These analyses reveal the properties of cfDNA in patients with brain cancer and open new avenues for noninvasive detection of these individuals. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-14T15:35:50.535661+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000987","title":"Integrated targeted deep sequencing reveals unique tissue-of-origin and donor cell-free DNA signatures in transplant recipients","description":"We have developed a targeted deep methylation sequencing assay that integrates cell-free DNA (cfDNA) tissue-of-origin analysis with donor-derived cfDNA quantification to non-invasively monitor transplant health. In this study, liver and kidney transplant recipients were assessed in conjunction with healthy controls to characterize the dynamic patterns of cfDNA release and clearance, and to identify distinct tissue injury signatures throughout the transplant journey.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-02T14:48:13.799053+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000988","title":"Transcriptome analysis of 32 pheochromocytoma and paraganglioma samples","description":"Pheochromocytomas and sympathetic paragangliomas (PPGL) are rare neuroendocrine tumors derived from chromaffin tissue of the adrenal medulla and sympathetic paraganglia, respectively. There is at the moment a lack of accurate biomarkers to predict the biologic behavior of a PPGL. The aim of this study was to investigate the biological behavior of localized and metastatic PPGL by comparing the genomic and transcriptomic landscapes of localized and metastatic PPGL, including PPGL samples with a non-metastatic phenotype at initial diagnosis that developed metachronous metastases during follow-up. The dataset presented here contains the RNA-seq data of 32 tumor samples (n=17 localized, n=15 metastatic).\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-30T16:34:57.733998+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000989","title":"In vitro profiling of human microbiota","description":"The goal of this study was to profile human fecal microbiota for their capacity to produce GABA. To this end \r\ne performed ex vivo fecal enrichments of donor stool in a range of different conditions that varied by carbon source and physicochemical environment. We then performed amplicon metagenomic sequencing to determine the community composition after enrichment.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000000990","title":"Fragmentomics profiling and quantification of plasma Epstein-Barr virus DNA enhance prediction of future nasopharyngeal carcinoma.","description":"This study evaluated the clinical utility of fragmentomics analysis of plasma Epstein-Barr virus (EBV) DNA in nasopharyngeal carcinoma (NPC) screening. The first-round EBV-positive blood samples from a two-round large-scale prospective NPC screening cohort were analyzed. The EBV DNA of subjects who developed NPC in the second round displayed a distinctive mononucleosomal size pattern, an NPC-associated end motif profile, and aberrations in methylation deduced by fragmentomics-based methylation analysis (FRAGMA). Subjects with these aberrant fragmentomics features and higher EBV DNA quantity showed a dramatically increased risk of NPC development, demonstrating the potential of plasma DNA fragmentomics in predicting future cancer risk.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":true},
{"accession_id":"EGAS50000000991","title":"Identification Of Pathogenic Mutations And Application Of Polygenic Risk Scores In Early-Onset Diabetes Patients","description":"Maturity-onset Diabetes of the Young (MODY) presents a diagnostic challenge. In this study we investigate the genetic background of Latvian early-onset diabetes patients, using whole-genome sequencing data. Additionally, we investigate the utility of previously published and available type 1 diabetes (T1D) and type 2 diabetes (T2D) polygenic risk scores in differentiating monogenic diabetes (MODY) from T1D and T2D cases.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-30T12:55:45.035112+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000992","title":"Predicting resistance to chemotherapy using chromosomal instability signatures","description":"The aim of this study is to assess whether three chromosomal instability signature biomarkers are capable of predicting resistance to standard chemotherapies, namely platins, taxanes and anthracyclines. As part of this study we compiled a proof of principle cohort of ovarian cancers treated with these therapies, profiled using the Illumina TSO500 panel. Analysis of these data demonstrated that accurate biomarker calling can be computed from these gene panel data.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-13T00:00:00+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000993","title":"Longitudinal Transcriptomic Profiling of Endothelial Progenitor Cells in Post-COVID-19 Patients: Insights at 3 and 6-Months Post-SARS-CoV-2 Infection","description":"Bulk RNA-sequencing analysis of endothelial cells isolated from post-COVID patients at 3 and 6 months post-infection, alongside healthy controls.\r\nThis study aims to identify differentially expressed genes in endothelial cells from post-COVID patients—at both 3- and 6-month time points—compared to those from healthy individuals. The objective is to uncover upregulated and downregulated pathways potentially associated with long-term consequences of SARS-CoV-2 infection.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-04T11:53:49.429596+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000994","title":"Human periportal liver assembloids recapitulate periportal liver tissue in vitro","description":"In vitro expansion of human hepatocytes from fresh patient tissues has not yet been achieved, limiting the possibility of modelling liver composite structures in vitro. Here, we developed human hepatocyte organoids from patient-donors that sustain the long-term expansion of hepatocytes in vitro. We profiled them using RNAseq to determine their gene expression pattern and compared this with the original native fresh isolated liver cell. Then, we used them to generate periportal liver assembloids by combining them with portal mesenchyme and cholangiocyte organoids. By increasing the number of mesenchymal cells we obtained structures with a fibrotic ratio of portal mesenchyme and we performed scRNAseq analysis to determine their gene expression and cell-cell interactions. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-29T12:17:59.022058+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000995","title":"CLUSTER RNAseq Study of Juvenile Idiopathic Arthritis patients in methotrexate cohort","description":"CLUSTER aims to discover novel disease mechanisms and biomarkers in children suffering from Juvenile idiopathic arthritis (JIA). Currently, little is known about the pathological disease mechanisms of JIA and there are no validated tools capable of predicting response or non-response to treatment. The study aims to identify biomarkers for treatment response using RNAseq technology. \r\nThe samples used in this study comes from blood samples that were collected prior to patients receiving methotrexate treatment (naive). These samples were then processed for PBMC isolation followed by sorting cells into 4 different immune cell types. All of these samples were then sequenced by NovaSeq6000.","abstract":null,"study_type":"RNASeq","pubmed_ids":[40681434],"external_links":null,"is_released":true,"released_date":"2025-07-09T09:46:43.40858+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000996","title":"Genetic differences between primary colorectal cancer and its paired synchronous and metachronous metastases ","description":"In this study we present for the first time the genetic differences associated with different chronicity of colorectal cancer liver metastases identified by whole-exome sequencing of 210 CRC samples. We focus on differences in primary tumors as we hypothesize that these are the cause of the differences in the time course of the disease. The results suggest that distinct tumor progression pathways account for different chronicity outcomes with ultimate impact on patient’s prognosis","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-03T09:13:43.402705+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000997","title":"Mutagenic impact of radiotherapy in B-cell lymphoma and multiple myeloma","description":"For refinement of the single base substitution and indel profiles induced by genotoxic platinum and ionizing radiation, DHL4 cells were treated with cisplatin or radiotherapy. Single cells from doses corresponding to lethal and half-lethal (medium), were expanded into single-cell derived colonies and then subjected to 60x whole genome sequencing. 16 bam files were generated.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-01T12:20:42.054687+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000998","title":"Mycobacterium_Induced_Granuloma","description":"Spatial transcriptomics of human Mycobacterium granulomas reveals Spatial and Functional Architecture of Immune Response and Tissue Remodeling","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-03T10:16:49.685278+02:00","is_deprecated":false},
{"accession_id":"EGAS50000000999","title":"Effects of GATA4-inhibiting compound 3i-2012 on HB-243 hepatoblastoma cells ","description":"In order to study the effects of GATA4 inhibition, HB-243 hepatoblastoma cells were treated with GATA4-inhibiting compound 3i-2012 for 24 hours. Total RNA was extracted and sequenced.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001000","title":"Human liver cholangiocyte organoids capture the heterogeneity of in vivo human liver ductal epithelium","description":"Human liver ductal epithelium is morphologically, functionally and transcriptionally heterogeneous. However, understanding the dynamics within human biliary/ductal epithelium has been hampered by the absence of an in vitro system that fully mimics its complex cellular heterogeneity. Here, we found that the human liver cholangiocyte (ductal-cell) organoids we previously published (Huch et al., 2015) are fairly homogenous and do not retain the cellular heterogeneity of the in vivo human biliary/ductal epithelium. Inspired by the knowledge of the in vivo niche, we refined our previous organoid culture medium to fully capture the cellular heterogeneity of the human ductal epithelium. We employed this refined system to analyse the interactions and relationships between the different human biliary epithelial cell states and discovered that acquiring a bipotent ductal cell state is necessary for differentiating the human ductal epithelium into functional hepatocyte-like cells. Our improved cholangiocyte organoid model represents a new platform to investigate cell plasticity and duct-to-hepatocyte differentiation in human liver.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-30T17:42:12.405839+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001001","title":"Spatial Transcriptomics Uncovers Tumor Microenvironment-Based Subtypes in Invasive Lobular Carcinoma","description":"Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer (BC); however, little is known about its tumor microenvironment (TME). Here, we investigated the spatial architecture of 43 hormone-receptor-positive, HER2-negative (HR+/HER2-) primary ILC samples, using spatial transcriptomics and detailed morphological annotation. By integrating morphology, spatial, and single-cell data, we mapped TME-related cell types, exploring their proximity to tumor cells and their enrichment in specific compartments. Clustering of spatial transcriptomics spots revealed significant inter- and intra-tumor heterogeneity, identifying pathways and cell types linked with disease outcomes. Morphological and gene expression data were finally integrated with a multimodal approach, leading to the identification of 4 new ILC subtypes based on TME heterogeneity. By using derived, specific gene expression signatures, these subtypes were identified and validated in external bulk RNA-seq/microarray datasets (SCAN-B and METABRIC), where differences in prognosis emerged.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-17T14:52:23.719787+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001002","title":"Arcagen - CNS domain","description":"Arcagen is an EORTC/SPECTA pan-European project that aims to recruit 1000 rare cancer patients from different tumour domains of EURACAN. This study collected samples from advanced or metastatic rare cancer from patients older than 12, and analysed them using Foundation Medicine next-generation sequencing (NGS) panels (FoundationOne CDx for FFPE samples or FoundationOne Liquid CDx for blood samples). Here we are submitting the dataset from patients with rare tumor from the central nervous system (n=61).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-02T14:17:22.54626+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001003","title":"MATISSE WES and bulk RNA-sequencing data","description":"High-risk cutaneous squamous cell carcinoma is frequently seen in frail, elderly patients and often requires mutilating surgical treatment and adjuvant radiotherapy (RT). The MATISSE trial (NCT04620200) was conducted to improve clinical prospects in CSCC patients eligible for extensive curative surgery, and evaluated early treatment response and immune dynamics following ultra-short neoadjuvant immunotherapy prior to standard of care surgery with or without radiotherapy. Fifty patients were randomized to receive two courses of nivolumab 3 mg/kg (NIVO, weeks 0&2) or nivolumab 3 mg/kg (weeks 0&2) and one course of ipilimumab 1 mg/kg (week 0 only, NIVO/IPI before surgery at week 4, with the primary objective being histopathological response based on residual viable tumor cells in the surgical specimen. Ten patients choose not to undergo surgery, of whom nine reached a clinical complete response during follow up, and were disease-free at median 34 months follow up. Serial tumor and blood samples at baseline, week 1, week 2 and week 4, enabled to investigate dynamical changes through bulk WES and RNA sequencing to potentially aid future de-escalation trials.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-09T11:28:35.861773+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001004","title":"Shifted assembly and function of mSWI/SNF family subcomplexes underlie targetable dependencies in endometriod carcinomas ","description":"The mammalian SWI/SNF (mSWI/SNF) family of chromatin remodelers govern cell type-specific chromatin accessibility and gene expression and assemble as three distinct complexes: canonical BAF (cBAF), Polybromo-associated BAF (PBAF), and non-canonical BAF (ncBAF). ARID1A and ARID1B are paralog subunits that specifically nucleate the assembly of cBAF complexes and are frequently dual deleted in highly aggressive differentiated endometrial carcinomas (DECs). Here, in cellular models and primary human tumors, we find that ARID1A/B-mediated cBAF loss results in increased ncBAF and PBAF biochemical abundance and function genome-wide to maintain the DEC oncogenic signature. Further, treatment of ARID1A/1B-mutant cell lines and PDX models in vivo with a clinical-grade SMARCA4/2 ATPase inhibitor, FHD-286, markedly attenuates cell proliferation and tumor growth, and synergizes with carboplatin-based chemotherapy. Taken together, these findings reveal the oncogenic contributions of shifted of mSWI/SNF family complex abundance and chromatin-level gene regulatory functions and suggest therapeutic utility of mSWI/SNF complex small molecule inhibitors in dedifferentiated endometrial carcinoma and other cBAF-disrupted cancer types.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-06T14:39:43.071199+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001005","title":"ConvexGating infers gating strategies from clusters in single cell cytometry data","description":"Manual gating remains the standard for identifying specific cell populations in flow cytometry and related technologies, but it is prone to subjectivity and inconsistency, particularly in high-dimensional or multi-center studies. This project introduces and validates ConvexGating, a machine learning-based tool that learns gating strategies in a data-driven, interpretable, and reproducible manner. The approach is applied to flow cytometry, CyTOF, and CITE-seq datasets to identify both known and previously ill-defined cell types with minimal contamination. Key populations such as CD8+ TEMRAs and plasmacytoid dendritic cells (pDCs) are examined. The goal is to improve consistency in single-cell analysis and enable more effective design of marker panels for sorting.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-27T10:14:06.244772+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001006","title":"PBAT sequencing of naïve human ESCs","description":"This project investigates the DNA methylation landscape of naïve human embryonic stem cells (hESCs) derived from human embryos, assessing the impact of ERK inhibition (ERKi).  Naïve ESCs were cultured in UXGL or PXGL media.  Post bisulphite adaptor tagging protocol was used to profile genome-wide DNA methylation. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-23T14:57:48.301733+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001007","title":"Cell Types and Molecular Mechanisms of Myopia in Humans, Primates and Mice","description":"The sclera is the opaque, fibrous outer layer of the eye's posterior segment and is known to be remodeled in myopia. This EGA study contains transcriptomes from human scleras, scleral fibroblast cell lines, and scleroids. We performed a comparative analysis of these transcriptomes in order to assess the similarity of the three tissues.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001008","title":"South African Blood Regulatory (SABR) Resource","description":"Functional genomics resources are critical for interpreting human genetic studies, however they are predominantly from European-ancestry individuals. Here we present the South African Blood Regulatory (SABR) resource, a map of blood regulatory variation that includes three South Eastern Bantu-speaking groups. Using paired whole genome and blood transcriptome data from over 600 individuals, we map the genetic architecture of 40 blood cell traits derived from deconvolution analysis, as well as expression, splice, and cell type interaction quantitative trait loci (QTL).","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-13T16:06:08.677272+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001009","title":"Relation between transcriptome, karyotype and age in cases of sex chromosome aneuploidies.","description":"Why women live longer than men is still an open question in human biology. Sex chromosomes have been proposed to play a role in the observed sex gap in longevity, and the Y male chromosome has been suspected of having a potential toxic genomic impact on male longevity. It has been hypothesized that transposable element (TE) repression declines with age, potentially leading to detrimental effects such as  somatic mutations and disrupted gene expression, which may accelerate the aging process. Given that the Y chromosome is rich in repeats, age-related increases in TE expression could be more pronounced in males, likely contributing to their reduced longevity compared to females.\r\nIn this work, we first studied whether TE expression is associated with the number of sex chromosomes in humans. We analyzed blood transcriptomic data obtained from individuals of different karyotype compositions: 46,XX females (normal female karyotype), 46,XY males (normal male karyotype), as well as males with abnormal karyotypes, such as 47,XXY, and 47,XYY. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-05-07T14:29:27.464554+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001010","title":"Reactive Lymph Node Gene Expression Profiling","description":"Reactive lymph nodes were processed as controls for the study.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-22T12:56:56.668243+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001011","title":"Anaplastic Large Cell Lymphoma Tumor Gene Expression Profiling","description":"Anaplastic large cell lymphoma tumor RNA-Seq","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-22T12:56:56.668243+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001012","title":"RAIDs cervical cancer project ","description":"The RAIDS project, launched by the Curie Institute in 2013, aims to molecularly characterize cervical cancer (CC) and improve patient risk stratification. As part of the Bio-RAIDS study (NCT02428842), next-generation sequencing was performed on tumor samples (whole-exome sequencing, shallow whole-genome sequencing and RNA-sequencing) identified frequent alterations, including PIK3CA (30%) and prognostic biomarkers like TERT, linked to poor progression-free survival. Over 50 clinically targetable mutations were found, offering new therapeutic opportunities. Transcriptomic analysis also linked specific genes and pathways to prognosis and tumor necrosis. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-27T14:32:51.8735+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001013","title":"Coding and regulatory somatic profiling of triple-negative breast cancer in Sub-Saharan African patients","description":"The burden of triple-negative breast cancer (TNBC) may be shaped by genetic factors, particularly inherited and somatic mutation profiles. However, data on this topic remain limited, especially for the African continent, where a higher TNBC incidence is observed. In the age of precision medicine, cataloguing TNBC diversity in African patients becomes imperative. We performed whole exome sequencing, including untranslated regions, on 30 samples from Angola and Cape Verde, which allowed to ascertain on potential regulatory mutations in TNBC for the first time. A high somatic burden was observed for the African cohort, with 86% of variants being so far unreported. Recurring to predictive functional algorithms, 17% of the somatic single nucleotide variants were predicted to be deleterious at the protein level, and 20% overlapped with candidate cis-regulatory elements controlling gene expression. Several of these somatic functionally-impactful mutations and copy number variation (mainly in 1q, 8q, 6 and 10p) occur in known BC- and all cancer-driver genes, enriched for several cancer mechanisms, including response to radiation and related DNA repair mechanisms. TP53 is the top of these known BC-driver genes, but our results identified possible novel TNBC driver genes that may play a main role in the African context, as TTN, CEACAM7, DEFB132, COPZ2 and GAS1. These findings emphasize the need to expand cancer omics screenings across the African continent, the region of the globe with highest genomic diversity, accelerating the discovery of new somatic mutations and cancer-related pathways. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-30T10:55:40.39346+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001014","title":"SPECIAL (scATACseq): Dissecting the melanoma ecosystem one cell at the time during immunotherapy ","description":"Characterising epigenome profiles of stage III/IV melanoma samples treated with ICB before and on treatment by single cell ATAC sequencing. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[38181739],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001015","title":"Adipose transcriptome and plasma metabolome responses after a 6-day very-low energy fast in obesity: a single-arm feeding trial (FASTOMICS-6)","description":"Background: Fasting and ketogenic diets have gained popularity due to potential health benefits, in part via autophagy and other protective processes. However, although the basic physiology of fasting is well-established, we lack a deeper understanding of mechanisms on the tissue level and associated metabolome changes, particularly in humans.\r\n\r\nMethod: 4 males and 9 females with severe obesity underwent a very-low-energy in-hospital feeding study (600 kcal/day). Plasma (n=13) and subcutaneous adipose tissue (sAT) samples (n=12) were collected in the morning before and after 6 days and analysed by GC-MS/MS and RNA-sequencing, respectively. Gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis were used to identify biological pathways and modules of affected genes and their correlation with plasma ketones and metabolites.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-26T10:52:37.434074+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001016","title":"Neoadjuvant gefitinib in resectable early-stage EGFR mutated non-small cell lung cancer (NSCLC): a window-of-opportunity study","description":"We conducted a window-of-opportunity study to uncover the dynamics and mechanisms of anti-tumour response through comprehensive in-depth tissue sequencing of resected tumours. In addition, we evaluated the safety, feasibility and efficacy of neoadjuvant gefitinib treatment prior to surgery for resectable EGFR mutated NSCLC.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001017","title":"Common origin and somatic mutation patterns of composite lymphomas and leukemias","description":"When two lymphomas occur concurrently or sequentially in a patient, it is a major question whether they derive from the same lymphocyte or hematopoietic precursor cell or developed independently. We studied four composite classic Hodgkin lymphomas (HL) and other mature B-cell lymphomas, and two composite mature B- and T-cell neoplasias by whole exome sequencing (WES) and analyzed shared somatic mutations in the lymphomas of these clonally related composite lymphomas, indicating their derivation from a common, pre-malignant precursor. Most identified mutations were restricted to one or the other of these lymphomas, likely explaining how distinct lymphomas developed from a common ancestral B cell. In the two B-cell/T-cell lymphoma cases, and a composite clonally unrelated HL/chronic lymphocytic leukemia, the lymphoma partners did not share any somatic mutations. In three cases, we identified potentially oncogenic variants also in cells serving as constitutional controls.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[40404986],"external_links":null,"is_released":true,"released_date":"2026-02-10T10:31:37.132473+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001018","title":"Personalized analysis of ctDNA for detection of molecular residual disease and recurrence in a cohort of surgically treated patients with head and neck squamous cell carcinoma","description":"Despite advances in multimodal treatment, survival for patients with advanced head and neck squamous cell carcinoma (HNSCC) has improved only modestly. The recent advent of tumor-informed assays capable of detecting circulating cell-free tumor DNA (ctDNA) has enabled early detection of molecular residual disease (MRD) and recurrence following curative therapy. We assessed ctDNA in plasma from 76 and saliva from 54 HNSCC patients, respectively, who received primary curative-intent surgery.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-20T14:10:17.844206+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001019","title":"Whole blood RNAseq from a large ALS case-control study at Univ of Michigan","description":"Patients with amyotrophic lateral sclerosis (ALS), a rare fatal neurodegenerative disease, face a lengthy diagnostic process, and, although most survive only 2 to 4 years from diagnosis, lack information regarding their specific anticipated disease course due to a lack of prognostic tools. Although ALS is a heterogeneous disease of varied etiology, peripheral immune system dysfunction is ubiquitous, reflected in altered whole blood transcriptome. Herein, we profiled whole blood gene expression by RNA sequencing in a large cohort of ALS cases versus controls. Several machine learning classifiers trained on our gene expression dataset predicted case-control status and survival, and integration analysis with external cohorts led to the identification of drug candidates. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-09T12:14:44.803891+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001020","title":"Single-cell multi-omics and mtDNA genotyping of human peripheral blood cells ","description":"In this study, we characterize human peripheral blood cells using mitochondrial single-cell ATAC-seq (mtscATAC-seq), which simultaneously profiles mitochondrial genomes and chromatin accessibility at single-cell resolution. This submission includes PBMCs from one healthy pediatric donor and one 80-year-old patient diagnosed with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-05T11:11:06.653576+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001021","title":"Molecular and cellular composition changes after neoadjuvant letrozole and palbociclib in early luminal breast cancer","description":"The NeoPAL trial compared neoadjuvant letrozole-palbociclib (LP) with chemotherapy (CT) in 103 patients with high-risk early luminal breast cancer. Deconvolution of bulk RNA-seq data revealed that myoepithelial cells, normal-like fibroblasts, FOLR2+ macrophages and SELL+ CD4+ T lymphocytes accumulated after treatment (p: 0.046 to 7.2e-07). All changes were similar between the LP and CT arms.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[30307466,35337692],"external_links":null,"is_released":true,"released_date":"2025-11-11T16:50:31.228312+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001022","title":"Single cell atlas of large B-cell lymphoma","description":"Large B-cell lymphomas (LBCL) are clinically and biologically heterogeneous lymphoid malignancies, shaped by complex tumor and microenvironments that play a critical role in disease progression. There has been no direct and comprehensive single-cell characterization of tumor microenvironment in LBCL that simultaneously captures lymphoid, myeloid, and stromal populations across a sufficiently large cohort to reveal reproducible and biologically meaningful patterns. Here, we performed single-nucleus multiome profiling, coupled with bulk DNA and RNA sequencing, on 232 tumor and control biopsies to comprehensively map cell subpopulations of LBCL. Through this integrative approach, we identified Lymphoma Microenvironment Archetype Profiles (LymphoMAPs)—distinct, reproducible patterns defined by the co-occurrence of functionally specialized cell subsets. We further characterized the cell-cell communication pathways that shape these transcriptional phenotypes within archetypes. Importantly, we discovered associations between specific LymphoMAPs and clinical and molecular features of LBCL, including response to CD19 CAR T-cell therapy. Our study provides a valuable resource of lymphoid, myeloid, and non-hematopoietic cell states in LBCL and offers a framework for understanding how the abundance and functional state of cells within the tumor microenvironment may drive inter-patient variability in therapeutic outcome.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-23T15:00:58.396217+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001023","title":"Clonal evolution of metastatic colorectal cancer under anticancer therapies","description":"To investigate the clonal evolution of metastatic CRC at the single-cell level, we performed WGS in 58 clonal organoids and 18 fresh-frozen (FT) bulk-tissue samples from surgically resected primary and metastatic tumors before and after anticancer therapies in 6 patients. This approach enabled detailed phylogenetic reconstruction of individual clones. We discovered the timing and burden of treatment-related mutations as well as the heterogeneous evolution in driver mutations and genomic rearrangements in late-stage clonal evolution under anticancer therapies in metastatic CRC.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-09T11:45:10.986827+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001024","title":"Targeted sequencing of Angioimmunoblastic lymphoma","description":"This study explores the recurrence of commonly mutated genes in lymphoma on a cohort of 137 angioimmunoblastic lymphoma (AITL) samples with a 713-gene targeted probeset panel. AITL is an aggressive T-cell lymphoma with bad prognosis. We aim to explore the therapeutic genomic landscape of AITL, focusing much on the EGFR-JAK/STAT mutations for potential repurposing of therapeutic agents onto AITL patients.\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001025","title":"Single-cell RNA-seq profiling of patient derived organoids","description":"The aim of this study was to profile developement of resistance to cancer treatments using organoids. Two patient derived colorectal cancer organoids were profiled using single cell RNAseq after treatment with a combination of different anticancer drugs. The organoids were profiled both after 4 weeks of treatment and after a drug holiday of 2 weeks.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-15T11:01:42.416448+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001026","title":"Bone morphogenetic protein-9 controls pulmonary vascular growth and remodeling","description":" Human PMECs from 10 donor lungs were isolated, cultured (passages 3 to 4), synchronized by serum starvation (0.3% FCS), and stimulated with 10 ng/mL BMP-9 for 4 h. Single-cell profiling was performed using the 10X Genomics Chromium RNA 3' V3.1 kit. Five experimental groups were analyzed using cell hashing and sequenced on an Illumina NextSeq500. Data were processed with Cell Ranger and Seurat for differential gene expression and functional enrichment analysis.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-03T14:28:52.486668+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001027","title":"Ultra-Low-Pass Whole Genome Sequencing of Cell-Free DNA for Large B-Cell Lymphoma","description":"While deep targeted DNA sequencing of liquid biopsies has shown prognostic utility in large B-cell lymphoma (LBCL), the routine clinical adoption of these assays remains limited due to their high costs. Here, leveraging a well-annotated cohort of encompassing both frontline and relapsed/refractory (R/R) LBCL, we profiled patient plasma samples with two complementary modalities – ultra-low-pass whole genome sequencing (ulpWGS) and deep targeted DNA sequencing, the former being a cost-effective method to profile large scale chromosomal abnormalities and estimate tumor burden. Our findings revealed a strong association of high cell-free tumor burden by both genomic profiling modalities with established measures of tumor burden and patient survival. Notably, the associations with survival remained statistically significant after accounting for international prognostic index scoring. Furthermore, we showed that del(17p) in circulating tumor DNA as detected by ulpWGS was strongly associated with TP53 mutation status and predicted for significantly inferior patient outcome in frontline but not R/R LBCL patients. Our study demonstrates that ulpWGS can provide robust prognostic biomarkers for both frontline and R/R LBCL, highlighting its broad applicability for risk stratification. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-05T16:27:26.711516+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001028","title":"A functional genomic links differential sperm methylation from overweight men to transposable element regulation in paternal origins of disease risk in children","description":"The occurrence of childhood neurodevelopmental disorders has been steadily increasing for decades yet we have little understanding of modes of inheritance implicated in these diseases. Epidemiology studies have revealed an association between an elevated paternal BMI and an increased risk for neurodevelopmental disorders in children, suggesting non-genetic modes of inheritance may be involved. Epigenetic marks –like DNA methylation at cytosines– are especially susceptible to environmental, diet and lifestyle changes. Yet, whether a man’s weight influences the sperm methylome and potentially impacts offspring development remains unresolved. Using MethylC capture (MCC)-sequencing, we identified over 38000 differentially methylated CpG (DMCs) in the sperm of men with an elevated BMI, with many occurring in regions that were enriched for neural gene and disease ontologies. Differentially methylated regions (DMRs) were enriched at transposable elements that can act as active enhancers during human zygotic genome activation, and at gene promoters for early lineage specification. These results suggest that sperm methylome alterations that are linked to elevated BMI may influence key embryonic transcriptional process, notably associated with trophectoderm and placental development. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-05T11:49:29.710032+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001029","title":" Spatial Dynamics of the Developing Heart (single-cell)","description":"Heart development relies on a topologically defined interplay between diverse cardiac cells. We finely curated spatial and single-cell measurements with high-resolution imaging-based transcriptomics validation to explore spatial dynamics during early human cardiogenesis. Analyzing almost 80,000 individual cells and 70,000 spatially barcoded tissue regions between the 5.5th and 14th postconceptional weeks, we identified 31 coarse- and 72 fine-grained cell states and mapped them to highly resolved cardiac cellular niches. We provide novel insight into the development of the cardiac pacemaker-conduction system, heart valves, and atrial septum, and decipher heterogeneity of the hitherto elusive cardiac fibroblast population. Furthermore, we describe the formation of the cardiac autonomic innervation and present the first spatial account of chromaffin cells in the fetal human heart. Our study, supported by an open-access, spatially centric interactive viewer, delineates the cellular and molecular architecture of the developing heart, offering links to genetic causes of heart disease.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-25T16:47:04.344007+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001030","title":"Single cell RNA-seq of two rare cases of human glioblastoma at multiple sampling points","description":"Glioblastoma is characterized by large cellular diversity whose complexity and organizing principles are only starting to be uncovered. Both neurodevelopment-like and mesenchymal-like cell states have been described in glioblastoma but the nature of the mesenchymal-like cell states remains unresolved. Here, we performed deep single-cell RNA sequencing of two rare glioblastoma cases where tissue could be sampled from tumor core to macroscopically normal cortex with the aim of understanding these tumor cell states.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-25T16:47:05.671005+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001031","title":"Human four week embryo head as reference for generating an enhancer compendium for neuronal and neural crest development using neural tube organoids.","description":"This study has the aim of generating an enhancer code compendium of early human neuronal and neural crest development. For this purpose, we generated human neural tube organoids from single cells from two induced pluripotent stem cell lines. The organoids were subject to combined single cell multiomics at four time points of differentiation. To evaluate the biological relevance of the cell types and states obtained from the organoids, we compared with data obtained from 10XGenomics single cell multiomics on the head of a single four weeks post conception human embryo.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-25T16:47:01.27571+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001032","title":"Circulating cell-free and extracellular vesicles-derived microRNA as prognostic biomarkers in patients with early-stage NSCLC: results from RESTING study","description":"Lung cancer, especially non-small cell lung cancer (NSCLC), has high mortality rates. Early-stage NSCLC shows a 50% relapse rate post-surgery, with most recurrences occurring within two years and a 5-year survival of only 30%. This study focuses on the prognostic value of circulating miRNAs in surgically treated ES-NSCLC patients, aiming to assess their predictive accuracy and compare them to standard prognostic factors.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[39169404],"external_links":null,"is_released":true,"released_date":"2025-07-28T17:51:30.556303+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001033","title":"The circulating cell-free DNA landscape in sepsis is dominated by impaired liver clearance","description":"Circulating cell-free DNA (cfDNA) is a promising molecular biomarker. However, its utility in severe infection remains poorly understood. Here, we isolated cfDNA from sepsis patients and controls, demonstrating a 41-fold increase in the amount of cfDNA in circulation during disease. We used sequencing to reconstruct cfDNA methylomes, fragmentation profiles, and nucleosome footprints across 58 samples. We observed no difference in cfDNA composition between patients and controls, challenging the idea that cfDNA increases due to higher immune cell death during sepsis. Instead, we suggest that liver dysfunction prevents efficient clearance of cfDNA during disease. This was supported by fragmentation and end-motif patterns, both of which showed evidence of cfDNA being exposed to circulating nucleases for a prolonged period, proportionally to the extent of liver dysfunction. Variation in cfDNA of megakaryocyte-erythroid progenitor origin was also a significant contributor in sepsis, increasing over time. Moreover, we showed that cfDNA retains nucleosome footprints with cell type-specific gene activity information. We developed a novel approach to study nucleosome phasing that successfully recovers tissue-specific signatures. By combining this with single-cell data, we demonstrated that sepsis patients with liver dysfunction have higher amounts of cfDNA derived from Kupffer cells and the liver parenchyma. In conclusion, we present the first high-throughput multi-modal study of cfDNA during sepsis, which will serve as a reference point for future studies on the role of this biomarker in critical illness.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-23T16:31:34.568216+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001034","title":"Single-cell and spatial atlas of steatotic liver disease-related hepatocellular carcinoma","description":"This study consists of the spatial transcriptomics data generated by :\r\n1. Visium CytAssist Spatial Gene Expression for FFPE (10x) for steatotic liver disease-associated hepatocellular carcinoma (SLD-HCC) (n=7) and non-SLD-HCC (n=5)  \r\n2. CosMxTM Human Universal Cell Characterization RNA Panel (1000-plex); NanoString, USA for n=4 SLD-HCC and n=4 non-SLD-HCC.\r\nThe goal of this data is to compare SLD-HCC vs non-SLD-HCC as well as response to immunotherapy","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-14T13:24:16.331993+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001035","title":"Role of KLK6 in human PDAC immunosuppression","description":"This study investigates the role of Kallikrein-Related Peptidase 6 (KLK6), a key regulator of the tumor microenvironment (TME), in pancreatic ductal adenocarcinoma (PDAC). We employed CRISPR/Cas9-mediated knockout (KO) strategies to disrupt KLK6 expression in cancer cells. To replicate critical aspects of the diseased TME, including altered tissue stiffness, we developed PDAC-specific hydrogel-based 3D culture systems. These synthetic constructs were composed of matrix metalloproteinase (MMP)-sensitive four-armed poly(ethylene glycol) (star-PEG)-heparin hydrogels. High-throughput RNA sequencing was then performed to assess transcriptomic changes associated with KLK6 depletion in this engineered microenvironment.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001036","title":"Genomic analysis of HGSOC using long read sequencing","description":"High-grade serous ovarian cancer (HGSOC) is characterized by widespread genomic instability, but genomic and epigenomic alterations within repetitive regions remain poorly understood. This study aims to investigate genomic and epigenomic variations in HGSOC using Oxford Nanopore long-read sequencing technology. High-molecular-weight DNA was extracted from cryopreserved, pre-treatment tumor samples and matched blood specimens. The objectives include developing a robust long-read sequencing analysis pipeline, identifying novel genomic and epigenomic variations, and exploring potential applications in future clinical and basic research.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-21T17:12:10.054972+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001037","title":"IgM heavy chain V(D)J library sequencing using varied PCR parameters","description":"When amplifying the rearranged V(D)J genes encoding antigen receptors during adaptive immune receptor repertoire sequencing (AIRR-seq), each cycle of the PCR can produce spurious “chimeric” hybrids of two or more different template sequences. To test the effects of PCR protocol variation on chimera formation in AIRR-seq, we produced IgM heavy chain V(D)J repertoire libraries under 8 conditions, varying the number of PCR cycles, indexing PCR template, input RNA, and extension time. Three donors were sequenced using all 8 conditions.  \r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-15T14:25:28.882104+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001038","title":"Single-cell transcriptomic data from tumor samples","description":"Extramedullary multiple myeloma is an aggressive form of multiple myeloma where the myeloma cells escape BM microenvironment and infiltrate distant tissues.We analyse using single cell techniques, the composition and functional state of major immune cells in EMM tumor microenvironment, T and NK cells. This dataset contains the singlecell RNAseq data used in the publication. It includes scRNAseq data from tumor samples across extramedullary multiple myeloma soft tissue (EMM) (n=5; 3 additional samples in the study are under accession numbers mentioned in the publication), EMM bone marrow (EMM_BM) (n=5), and relapsed/refractory multiple myeloma (RRMM_BM) BM (n=6). ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-22T14:22:38.467409+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001039","title":"Single cell spatial transcriptomics identifies coordinated cellular programs associated with good prognosis in microsatellite stable colorectal cancer","description":"Colonic resections were obtained from patients operated for sigmoid colon cancer at Akershus University Hospital (Ahus, 1478 Lørenskog, Norway). The resected colon was immediately examined by an experienced pathologistand macroscopically normal colon, at least 10 cm from the tumor, in addition to tumor tissue were placed in vials with RPMI 1640 and put on ice for transport. The study was performed in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants, and the study was approved by the Regional Committee for Medical Research Ethics (REK, 2018/703, Health Region South-East, Norway). For scRNA-seq, 6 colon specimens from caecum or sigmoid colon were obtained (age 60-79, 4 males). None of the patients had autoimmune, infectious or inflammatory diseases, nor received neoadjuvant chemotherapy or radiation therapy before the operation. All patients were operated following the national guidelines.\r\n\r\nCellular suspensions (∼15000 cells, with expected recovery of ∼7500 cells) of sorted CD45+ HLA-DR+ CD14+ macrophages from colonic mucosa and tumor were loaded on the 10X Chromium Controller instrument (10X Genomics) according to the manufacturer’s protocol using the 10X GEMCode proprietary technology. All samples from individual patients\r\nwere loaded in one batch. The Chromium Single Cell 3´ v2 Reagent kit (10X Genomics) was used to generate the cDNA and prepare the libraries, according to the manufacturer’s protocol.\r\nThe libraries were then equimolarly pooled and sequenced on an Illumina NextSeq500 using HighOutput flow cells v2.5. A coverage of 400M reads per sample was targeted, in order to obtain 50 000 reads per cell. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001040","title":"Extrachromosomal DNA-driven oncogene dosage heterogeneity determines therapy response in neuroblastoma","description":"Characterization of ecDNA copy number-dependent plasticity of neuroblastoma patient-derived xenograft models. Data corresponds to single-cell G&T sequencing from an untreated neuroblastoma PDX and single-cell multiome ATAC + gene expression sequencing of a SHH medulloblastoma tumor.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-02T12:16:00.763849+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001041","title":"SCI-MAP: Single Cell Microgel embedded iPS-cells to map molecular variability of cell differentiation using a systems biology approach.","description":"In the SCI-MAP project we will map cell states encountered across a previously established 49 day in vitro chondrogenic differentiation protocol. We do this to optimise the differentiation process for therapeutic and in vitro modelling ends. We collect epigenetic open chromatin and phenotypic transcriptome data to determine cell states and so performed single nucleus sequencing in two modalities: RNA- and ATAC-sequencing. Data was collected in a time series experiment at 7 points: Days 0, 3, 6, 8, 14, 21, and 49, starting with the first pilot data from day 21 (D21).","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-20T16:27:37.675503+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001042","title":"Ultra-long sequencing for contiguous haplotype resolution of the human immunoglobulin heavy chain locus","description":"Genetic diversity within the human immunoglobulin heavy chain (IGH) locus influences the expressed antibody repertoire and susceptibility to infectious and autoimmune diseases. However, repetitive sequences and complex structural variation pose significant challenges for large-scale characterization. Here, we introduce a method that combines Oxford Nanopore ultra-long sequencing and adaptive sampling with a bioinformatic pipeline to produce haplotype-resolved, annotated IGH assemblies. Notably, our strategy overcomes prior limitations in phasing resolution, enabling single-contig haplotype assemblies that span the entire IGH locus. We applied this method to four individuals and validated the accuracy of the IGH assemblies using Pacific Biosciences HiFi reads, demonstrating near-complete sequence congruence, detecting only indels with a high degree of confidence. Moreover, when applied to the reference material HG002, our pipeline revealed no base differences and a limited number of indels compared with the Telomere-to-Telomere genome benchmark across the IGH region. Importantly, in the four individuals, our approach uncovered 30 novel alleles and previously uncharacterized large structural variants, including a 120 kb duplication spanning IGHE to IGHA1 and an expanded seven-copy IGHV3-23 gene haplotype. These findings underscore the power of our method to resolve the full complexity of the IGH locus and uncover previously unrecognized variants that may affect immune function and disease susceptibility. Thus, our method provides a strong basis for future immunological research and translational applications.","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-13T12:41:40.065214+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001043","title":"Excised DNA Circles from V(D)J Recombination Promote Relapsed Leukaemia","description":"In this study, we show that ESCs replicate and persist through many cell generations. High ESC copies at diagnosis of BCP-ALL strongly correlate with subsequent relapse. These data provide the first demonstration that the V(D)J recombination by-product, when replicated to elevated levels, potently associates with the V(D)J recombinase to cause adverse disease outcomes.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-01T15:41:14.020746+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001044","title":"Liquid Biopsy Detection of Tumor-specific Structural Variants in High Grade Serous Ovarian Cancer","description":"WGS Liquid Biopsy. Recurrence is frequent for most patients with high grade serous ovarian cancer (HGSOC), even after effective chemotherapy induced remission. However, after achievement of complete clinical response, the minimal residual disease is often insufficient for genomic analysis. Therefore, methods to interrogate the clonal composition and molecular properties of minimal residual disease are needed to better understand the mechanisms of HGSOC relapse. To address this unmet need, we developed and validated a novel cfDNA-based approach for tracking disease burden using NGS-informed tumor specific structural variants (SVs). Methods: The optimization of the methodology was first performed using synthetic cfDNA generated by ultrasonication of gDNA from ovarian cancer cell lines. Following the optimized workflow, whole genome sequencing of multisite biopsies from pre-treatment HGSOC patients were performed and high confidence SVs were called by consensus of multiple published SV callers. Real-time PCR and digital droplet PCR (ddPCR) were used for assays development. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-01T15:42:45.040568+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001045","title":"Total RNA expression in benign ovarian and malignant ovarian tumours","description":"This study investigates the total RNA expression profiles of fresh-frozen ovarian tumors, providing a comprehensive analysis of 112 samples from 111 women in Sweden, two samples being replicates. The dataset includes 18 benign and 94 malignant tumours, collected as part of the U-CAN initiative from Uppsala Biobank.\r\n\r\nThe sequencing data offers valuable insights into ovarian tumour biology and can be used to enhance understanding of tumour classification and molecular characteristics.","abstract":null,"study_type":"RNASeq","pubmed_ids":[40506476],"external_links":null,"is_released":true,"released_date":"2025-06-24T13:24:48.067879+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001046","title":"Single cell RNA sequencing of peripheral blood HSPC from patients with sickle cell anemia and healthy donors","description":"Neutrophils and monocytes are critical contributors to the pathophysiology of sickle cell anemia (SCA) and are persistently elevated in patients' circulation. While chronic hemolysis has been implicated in this leukocytosis, the underlying mechanisms remain incompletely understood. Our data show a myeloid-skewed transcriptional signature in early progenitor populations, including multipotent progenitors (MPPs) and hematopoietic stem cells (HSCs). Notably, we identify upregulation of the type I interferon signaling pathway in HSPCs as a key driver of early myeloid programming in SCA.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-15T14:22:32.841602+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001047","title":"B cell receptor silencing reveals origin and dependencies of high-grade B cell lymphomas with MYC and BCL2 rearrangements","description":"High-grade B cell lymphomas with MYC and BCL2 rearrangements (HGBCL-DH-BCL2) represent highly aggressive Germinal center (GC) derived B cell malignancies with dismal prognosis and limited therapeutic options. In the present study, we investigated the expression of BCR complex components, including immunoglobulin (IG) heavy (H) and light (L) chains, and CD79A and CD79B signaling subunits in HGBCL-DH-BCL2, scoring 65% of cases with undetectable IGH immunoreactivity (IGHUND). Transcriptomics (bulk RNA-seq) and genetic (whole exome/genome sequencing) analyses indicated that IGHUND and IGH+ HGBCL-DH-BCL2 lymphomas represent distinct biological entities. Specifically, IGHUND HGBCL-DH-BCL2 exhibit a GC DZ-like molecular program, and select subset-specific gene mutations pointing to distinct evolutionary trajectories respect to the IGH+ counterparts. IG profiling revealed that IGHUND HGBCL-DH-BCL2 preserved potentially productive, hypermutated IGH variable (V) gene rearrangements, indicating a selective advantage conferred to the malignant B cells by residual IGH molecules. Accordingly, disruption of the productively rearranged IGHG1 gene in BCRnull HGBCL-DH-BCL2 cell line model confirmed the dependency on IGH expression for optimal fitness. Using transcriptomics and in situ RNA-scope analysis, we reported that IGHUND HGBCL-DH-BCL2 originated from IG-class switched GC B cells, while IGH-expressing tumors were selected for continuous IGM expression. Moreover, while IGH+ HGBCL-DH-BCL2 favor IGM/IG-Kappa expression, IGHUND counterparts complete IG-Lambda light chain rearrangements. Notably, BCR silencing, caused by accelerated IGH turnover and reduced IGH expression, precedes HGBCL-DH-BCL2 onset, inducing RAG1/2-dependent IG light chain editing and eventually facilitating t(8;22)/IGL::MYC translocations. Finally, IGH silencing observed in HGBCL-DH-BCL2 cell models, which leads to intracellular retention/silencing of CD79B, results in reduced sensitivity to the CD79B-targeting antibody-drug conjugate Polatuzumab-vedotin. Collectively, HGBCL-DH-BCL2 originates from isotype-switched t(14;18)+ GC B cells that undergo IG light chain editing fuelling intra-clonal diversification, BCR silencing, and the acquisition of t(8;22) translocation, while preserving IGH dependency.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-26T15:08:01.333142+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001048","title":"Transcriptomic profiling of circulating regulatory T cells from follicular lymphoma patients before and after Lenalidomide treatment","description":"Lenalidomide has demonstrated a favorable efficacy profile in follicular lymphoma (FL) in combination with anti-CD20 antibodies. However, in vivo administration of Lenalidomide in FL patients triggers a proliferation of functional regulatory T cells (Tregs), and a high percentage of Tregs before and along the course of treatment with Lenalidomide/anti-CD20 combination is of poor prognosis. In this study, we evaluated the impact of Lenalidomide on circulating Treg in 3 FL patients using single cell RNA sequencing (scRNAseq). For this purpose, we took advantage of the GALEN clinical trial (NCT01582776), where Lenalidomide was initiated one week before starting the anti-CD20 antibody Obinutuzumab, allowing us to compare the transcriptomic profile of immune cells before (D0) and at day 7 (D7) of treatment by Lenalidomide alone.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-15T14:26:34.366245+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001049","title":"Identification of novel RNA isoforms in human osteosarcoma","description":"Three osteosarcoma (OS) tumors were obtained from separate human subjects. RNA isolated from each tumor sample was used to perform both long-read PacBio sequencing and illumina short-read sequencing. Data analysis was performed using a custom workflow to identify novel RNA isoforms enriched in OS. Novel RNA isoforms and respective coding proteins are key targets for downstream analysis and eventual development of anti-cancer therapies.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001050","title":"miRNA seq","description":"miRNA Sequencing of olfactory mucosa (OM) cells derived from cognitively healthy and individuals with AD exposed to traffic-related ultrafine particles (UFPs) for 72h in submerged cultures. The UFPs used for exposures were: A0 and A20. Exposures were compared to the corresponding blank samples.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-26T15:08:47.676712+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001051","title":"DNAmet","description":"DNAmet analysis of olfactory mucosa (OM) cells derived from cognitively healthy and individuals with AD exposed to traffic-related ultrafine particles (UFPs) for 72h in submerged cultures. The UFPs used for exposures were: A0 and A20. Exposures were compared to the corresponding blank samples.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-26T15:08:46.216362+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001052","title":"Cannabis impacts female fertility as evidenced by an in vitro investigation and a case-control study","description":"Single immature human oocytes were cultured in vitro (24h) either under control, THC1 () or THC2 (100 ng/mL Δ9-THC, 50 ng/mL 11-OH-THC, 200 ng/mL 11-COOH-THC) conditions. Oocytes were collected and subjected to SmartSeq v4 cDNA conversion, library prep (Nextera XT)), and sequencing (NovaSeq S4). The goal of this study was to determine the impact of THC on the human oocyte transcriptome. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-02T19:01:43.731249+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001053","title":"3D chromatin architecture identification in B cells by MicroC","description":"MicroC libraries were built using B cells from three healthy donors to investigate the 3D chromatin architecture at nucleosome resolution. This approach enables detailed mapping of chromatin interactions, including loops, domains, and higher-order structures. The resulting data can be used to compare the spatial genome organization in B cells with that of other cell types, shedding light on cell-type-specific chromatin regulation.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001054","title":"Clinical Outcomes of 344 Diffuse Large B-Cell Lymphoma patients","description":"This study examines clinical outcomes of patients with diffuse large B-cell lymphoma (DLBCL). We analyzed a cohort of 344 patients from the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). To protect patient confidentiality, all samples were pseudonymized. The dataset includes clinical key characteristics, such as patient age at diagnosis, sex, ECOG performance status, disease stage, serum lactate dehydrogenase levels, bulky disease, bone marrow involvement, extranodal involvement, and B-symptoms. We used these data alongside proteomic and transcriptomic profiles to explore relationships between clinical features and molecular signatures, reconstructing regulatory networks. Insights from this integrative analysis aim to identify key pathological drivers and biomarkers of DLBCL progression, ultimately informing improved risk stratification and targeted therapeutic approaches.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-16T12:49:07.810397+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001055","title":"Sequence data to study genomic CNVs that drive apoptotic resistance and relapses on immune checkpoint inhibitors ","description":"This project investigates the genomic mechanisms underlying acquired resistance to immune checkpoint inhibitors (ICIs) across tumor types, addressing the critical clinical problem of treatment relapses where the molecular basis remains poorly understood. Through integrative genomic analyses of longitudinal clinical melanomas, functional CRISPR-Cas9 screens, and human and murine melanoma models, the study demonstrates that copy-number variant (CNV)-driven subclonal evolution is a primary driver of clinical relapses. The research identifies resistance-driver genes targeted by CNVs, including pro-apoptotic gene deletions and anti-apoptotic gene amplifications, which collectively downregulate apoptotic priming in resistant cells. The findings establish that modulating the apoptotic threshold can prevent or reverse ICI resistance, positioning CNV evolution as a key driver of acquired resistance and identifying apoptotic regulation as a therapeutic target to combat resistance evolution.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-07T18:49:23.28185+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001056","title":"Genomic Signatures of Intestinal Metaplasia in Six Countries with Varying Incidence of Stomach Cancer ","description":"Intestinal metaplasia (IM) is a pre-cancerous condition associated with gastric cancer (GC), a deadly malignancy with varying geographic incidence. Performing a genomic analysis of over 1,500 IM samples from six countries, we identified 46 significantly mutated genes. We observed IM driver genes associated with high-risk populations and worse prognosis (ARID1A), members of the KRAS/MAPK signalling pathway (KRAS, BRAF, MAP2K1, MAP3K1, MAP2K4, NF1), and altered mucosal immunity (PIGR). ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-07T13:43:29.055437+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001057","title":"RNA-seq of tumor samples from clear cell renal cell carcinoma patients included in the Translational Program of the NIVOREN GETUG-AFU-26 trial","description":"Study on RNA-seq data from tumor tissue samples of primary tumors of advanced clear cell renal cell carcinoma patients enrolled in the NIVOREN GETUG-AFU-26 trial  who consented to and participated in the translational program. The goal of this study was to assess previously published gene expression signatures and evaluate their association with the benefit and/or resistance to nivolumab, as well as  their association with circulating soluble factors.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-28T16:31:10.025505+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001058","title":"10X whole single cell RNA-seq from pre-frontal cortex biopsy","description":"The biopsy procedure was performed by a standard operative procedure under general anaesthesia. The placement of burr hole on the frontal lobe, opening of dura and cortex was performed in a routine fashion for VP shunt or VCS surgery. The biopsy was sharp dissected with knife through the leptomeninges, forming a tissue block consisting of cortex and subcortex, and placed in a sterile tube containing CSF. Fresh tissue sample processing was performed within the hours after surgery. The tissue was dissociated followed by red cell and debris removal and counting of the cells to be sequenced with (scRNA-seq; 10x Genomics). After dissociation only non neuronal cells were retrieved. \r\n","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-14T15:52:35.645327+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001059","title":"Defining Human Inner Ear Development: HIEDRA snRNAseq Atlas and Inner Ear Organoid Refinement ","description":"We present the Human Inner Ear Development snRNAseq Atlas (HIEDRA), a single-nucleus transcriptomic resource spanning fetal weeks 7–15. HIEDRA captures key events such as cochlear and vestibular sensory differentiation and secretory epithelium formation. It identifies novel markers distinguishing cochlear and vestibular lineages, implicates specific signalling pathways in secretory cell differentiation, and maps disorder-associated genes to vulnerable cell types. This dataset provides a foundation for modeling inner ear development and disorders, supporting regenerative and precision medicine. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-07T15:43:57.423153+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001060","title":"DHODH is a synthetic-lethal vulnerability in BCOR-deficient acute myeloid leukemia","description":"Acute Myeloid Leukemia (AML) remains challenging to treat, especially in cases with mutations in the BCL-6 co-\r\nrepressor (BCOR), which are associated with poor prognosis and chemo-resistance. In this study, we reveal a\r\nsynthetic lethal interaction between BCOR and dihydroorotate dehydrogenase (DHODH). We demonstrate that\r\nBCOR-deficient cells have a heightened sensitivity to DHODH inhibitors such as brequinar and leflunomide, that\r\nare already in clinical use. We confirm that DHODH inhibition selectively induces cell death in BCOR-mutant\r\ncells in multiple cellular models, in malignant and non-malignant cells, through chemical and genetic\r\nmanipulation. Interestingly, we find that the dependency on DHODH does not stem from its role in de novo\r\npyrimidine biosynthesis disruption. Rather, DHODH’s role in the electron transport chain, essential for mitigating\r\nreactive oxygen species, may be the physiological vulnerability that pushes BCOR-mutant cells toward cell death\r\nwhen DHODH is inhibited. DHODH inhibitors could be repurposed as targeted therapies for BCOR-mutant\r\ntumors, offering a promising strategy for precision medicine in AML and other cancers.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-15T13:52:27.831811+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001061","title":"ResolveCRPS study - RNA-fragment sequencing from snap-frozen skin biopsies","description":"Complex Regional Pain Syndrome (CRPS) is a disabling pain disorder with unclear cutaneous molecular mechanisms. To identify gene-expression signatures linked to pain intensity and disease progression, we profiled the local transcriptome of CRPS-affected skin. 42 patients agreed to skin biopsies from the CRPS-affected area, which underwent low-input total RNA-seq. Full experimental and bioinformatics protocols are provided in the associated publication and its supplementary material.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-10T17:01:13.850812+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001062","title":"Clinical Utility of Breast cancer Research by Inocras, Catholic university hospital and Samsung medical center","description":"Breast cancer remains a major global challenge. To comprehensively characterize its genomic landscape and clinical significance, we analyzed whole genome sequences from 1,364 clinically annotated breast cancers, integrating transcriptome data from most of the tumors.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-16T17:08:19.719381+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001063","title":"Investigation of BK Polyomavirus (BKPyV) and Molecular Signatures in UC specimens from Taiwan","description":"Urothelial carcinoma (UC) is the most prevalent cancer of kidney transplant recipients in some regions. The integration of BK polyomavirus (BKPyV) genome into the human genome is observed in some cases of UC. The prevalence of aristolochic acid (AA) mutational signatures in urothelial carcinoma is high in the general population of Taiwan. To better understand the mechanisms of UC carcinogenesis in kidney transplant recipients, 19 UC specimens were analyzed by whole genome sequencing (WGS) and Hybrid Sequencing. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-09T17:26:15.518527+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001064","title":"MorphoITH: A Framework for Deconvolving Intra-Tumor Heterogeneity Using Tissue Morphology","description":"This study introduces MorphoITH, a framework for deconvolving intra-tumor heterogeneity (ITH) in clear cell renal cell carcinoma (ccRCC) based on tissue morphology from histopathological slides. The study tested MorphoITH's ability to capture different aspects of morphology and to reflect genetic ITH. The data deposited here is derived from a morphology guided multi-regional sequencing dataset used to study the relationship between morphology and genetic evolution. This dataset consists of whole exome sequencing of tumor from multiple sites and adjacent normal samples which were collected from two patients treated in affiliated hospitals of the University of Texas Southwestern Medical Center (UTSW), including Parkland Hospital.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-02T19:23:01.059766+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001065","title":"Nanopore sequencing of FSHD, BAMS and healthy control fibroblast cell lines","description":"The goal was to resolve the complex genetic and epigenetic structures of D4Z4 alleles, a macrosatellite whose desilencing results in FSHD.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-16T17:47:37.454647+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001066","title":"Assessing gene expression profiling from FFPE Patient Samples: A Comparison of Two Library Preparation Approaches and Recommendations","description":"Next-Generation Sequencing (NGS) has transformed cancer research and clinical practice,\r\nwith Whole Exome Sequencing (WES) driving advances in mutational profiling and\r\npersonalized oncology. Yet, transcriptomic signatures remain essential for understanding\r\ndisease mechanisms, including therapy resistance pathways. RNA sequencing (RNA-seq),\r\nhowever, faces unique challenges when dealing with low-input or degraded RNA, as often\r\nfound in archival formalin-fixed paraffin-embedded (FFPE) tissues. Although previous\r\nstudies have compared library preparation protocols, rapidly evolving technologies call for\r\nupdated evaluations. Here, we present a direct comparison of two FFPE-compatible stranded\r\nRNA-seq library preparation kits: TaKaRa™ SMARTer® Stranded Total RNA-Seq Kit v2\r\n(Kit A) and Illumina Stranded Total RNA Prep Ligation with Ribo-Zero Plus (Kit B). Both\r\nkits generated high-quality RNA-seq data, yet important differences emerged. Notably, Kit A\r\nachieved comparable gene expression quantification to Kit B while requiring 20-fold less\r\nRNA input, a crucial advantage for limited samples, albeit with increased sequencing depth.\r\nWe critically discuss these results in relation to RNA availability, technical performance,\r\ncost-effectiveness, processing time, and automation potential, offering practical guidance for\r\nselecting optimal RNA-seq strategies in clinical and translational research settings","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-04T14:06:17.383504+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001067","title":"We want to create an atlas of epithelial human rectum cells in healthy and people who suffer from IBS-C or IBS-D","description":"This submission is about 40 healthy and IBS human rectum samples. The goal of this study is to create an atlas of epithelial rectal cells. This is going together with the previous submission of colonic epithelial cells","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001068","title":"Single cell transcriptomics of human kidney organoid endothelium reveals vessel growth processes and arterial maturation upon transplantation","description":"Human induced pluripotent stem cell-derived kidney organoids have potential for disease modeling and regenerative medicine purposes. However, they lack a functional vasculature in in vitro culture. Here, we transplanted kidney organoids at day 7+12 of differentiation in the coelomic cavity of chicken embryos. We then compared human endothelial cells from transplanted organoids to their respective untransplanted controls at d7+13 and d7+20 using scRNAseq. We demonstrate metabolic and phenotypic effect of transplantation with increased endothelial cell proliferation and differentiation to a fetal-like renal arterial/afferent arteriolar phenotype.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-24T13:11:12.434282+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001069","title":"Myeloid cell networks govern re-establishment of original immune landscapes in recurrent ovarian cancer","description":"Immunotherapy has produced disappointing results in recurrent ovarian cancer (OC).\r\nHowever, the prognostic value of tumour-infiltrating lymphocytes (TILs) is largely based\r\non the analysis of treatment-naive tumours. To understand the immunobiology of\r\nrecurrent cancers, and their evolution, we profiled a total of 697 OC tumour samples\r\n(566 primary and 131 recurrent including 69 patient-matched samples) from 595\r\npatients of five independent multi-institutional cohorts. By capturing heterogeneous TIL\r\ndistributions, we identified four immune phenotypes associated with differential\r\nprognosis, TILs states and TILs:myeloid networks, which dictate malignant progression\r\nafter chemotherapy and recurrence. Notably, recurrent tumours recapitulate the\r\nimmunogenic landscapes of original cancers. Mirroring inflamed human OC, preclinical\r\nrecurrent Brca1mut tumours maintained activated TILs:dendritic cells (DCs) niches but\r\nevaded immune control through COX/PGE2 signaling upregulation. Conversely,\r\nrecurrent Brca1wt tumours displayed loss of TILs:DCs niches and accumulated\r\nimmunosuppressive myeloid networks featuring Trem2/ApoEhigh TAMs and\r\nNduf4l2high/Galectin3high malignant states. Our study highlights that persistent\r\nimmunogenicity in recurrent OC is governed by the BRCA-dependent crosstalk\r\nbetween dissimilar myeloid cells and TILs. We propose new targets to modulate the\r\nmalignant and TAM compartments which improve efficacy of standard of care\r\nchemotherapy in mouse OC models with HR deficiency.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-14T09:55:48.836752+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001070","title":"Single nuclei RNA sequencing on Primary and Maladaptive FSGS patient samples","description":"We used single-nucleus RNA-sequencing to identify differentially expressed transcriptional signatures in kidney biopsies of well-phenotyped primary vs. maladaptive FSGS patients. We included cryopreserved kidney biopsy cores from adult patients with newly diagnosed primary FSGS (n = 9, all nephrotic), maladaptive FSGS (n = 9, not nephrotic), proteinuric controls (PLA2R-positive membranous nephropathy, n = 3), and healthy controls (n = 4). We identified 120,751 high-quality nuclei, including 2,471 podocytes and 1,574 parietal epithelial cells (PECs).","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-01T16:45:03.500416+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001071","title":"Emirati Genome Project subset of 43,608 WGS samples for population-scale variant discovery and allele frequency mapping. ","description":"Here, we present a comprehensive genomic characterization of a cohort of 43,608 Emirati genomes sequenced as part of the Emirati Genome Program (EGP). This study identified more than 421 million single nucleotide variants and indels and more than 600 million copy number- and structural variants. Small variants had 756 million molecular effects annotated. Of the identified variants, 69.04% were observed with more than one allele. Of 7.7 million polymorphic variants having an allele frequency (AF) of more than 5% in EGP, 1,348 have a predicted deleterious effect on a protein. Characterization of global variation reveals that EGP represents a genetic continuum encompassing the range of African, Asian, and European populations. It is best described by two Arabian, an Eurasian, and an African component, with the predominant Arabian component linked to mitochondrial haplogroups J and T, which are commonly attributed to the Middle East. Various aneuploidies of sex chromosomes were detected in 93 individuals overall and of chromosome 21 in 41 individuals. The median inbreeding coefficient and cumulative runs of homozygosity (ROHs) lengths were increased due to extensive consanguinity, being largest in the groups with Arabian main ancestry components and higher than reported for Qatar.\r\nFamilies were identified based on genetic relatedness and classified into 264 families with unrelated parents and 247 families with third- and fourth-degree consanguineous parents. Representative consanguineous pedigrees of families in EGP were outlined. Cumulative ROHs were affected by the main ancestry component and significantly increased in offspring of consanguineous parents, with a pronounced difference between 3rd and 4th-degree relatedness. Investigation of cumulative AFs of variants causing Mendelian diseases highlighted genes related to alpha- and beta-thalassemia (HBB, HBA2). It showed a high burden of variants causing severe recessive diseases, metabolic and retinal disorders, and hearing loss. In summary, EGP represents a landmark effort in characterizing the genetic diversity of the Emirati population, leveraging the largest Middle Eastern cohort reported to date.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-18T11:47:38.27139+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001072","title":"Ancient tree-topologies and gene-flow processes among human lineages in Africa","description":"The deep history of human evolution in Africa remain intensely debated. We produced 73 novel high-quality whole genomes from 14 Central and Southern African populations with diverse cultural practices. With extensive simulations and machine-learning Approximate Bayesian Computation inferences, we reconstruct jointly their complex history of divergences and migrations. We find vast genome-wide diversity within and among populations, often uncorrelated with geography and cultural practices. This demonstrates the necessity to explicitly consider local genomic patterns, without merging samples indiscriminately into larger a priori categories, to reconstruct human evolutionary histories. We find that tree-like evolutions with long periods of drift between short periods of unidirectional gene-flow best explain the data, and that the lineage ancestral to Khoe-San populations diverged around 300,000 years ago from a lineage ancestral to rainforest hunter-gatherers and neighboring agriculturalists. We also find that short periods of ancient and recent gene-flow coincide with epochs of major ecological and cultural changes in Sub-Saharan Africa.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-09T16:06:38.681878+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001073","title":"Germline WES-data of pediatric cancer patients with variants in HBOC-related genes","description":"This study focused on the identification of (likely) pathogenic germline variants (LP/PV) in 25 adult-onset HBOC-related genes in a cohort of 372 pediatric cancer patients. The cohort was sequenced on Illumina platforms. The files uploaded here belong to the 27 individuals with such a LP/PV.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001074","title":"DynaTag for efficient profiling of transcription factors in small samples and single cells","description":"Systematic discovery of transcription factor (TF) landscapes in low-input samples and at single cell level is a major challenge in the fields of molecular biology, genetics, and epigenetics. To address this, we present here cleavage under Dynamic targets and Tagmentation (DynaTag), which allows robust mapping of specific TF-DNA interactions via the use of a physiological salt solution during sample preparation. Using this method, we revealed occupancy alterations for 15 different TFs in stem cell and cancer tissue models. Of note, we showcased for NANOG, MYC, and OCT4 differentially occupied genomic loci during stem cell differentiation, both in bulk and at single-cell resolution. DynaTag demonstrated superior signal-to-background ratio and occupancy resolution in comparison to CUT&RUN and ChIP-seq. In addition, a model for small cell lung cancer chemotherapy treatment in vivo showed increased chromatin occupancies of the gain-of-function mutant P53 p.R248Q, FOXA1, and MYC at altered gene pathways, such as epithelial-mesenchymal-transition. Altogether, these results highlight the technical advancement of DynaTag to uncover TF landscapes in cell models and in tissues of a complex disease model.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-01T15:34:38.921411+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001075","title":"KAT6A and KAT7 Histone Acetyltransferase Complexes Are Molecular Dependencies and Therapeutic Targets in NUP98-Rearranged Acute Myeloid Leukemia","description":"NUP98 fusion oncoproteins (FOs) are a hallmark of childhood acute myeloid leukemia (AML). NUP98 FOs drive leukemogenesis through phase-separated condensate formation and maintenance of an active chromatin landscape at stem cell-associated genes in cooperation with epigenetic regulators. Here we show that MYST family histone acetyltransferase (HAT) complex proteins including KAT6A/MOZ, KAT7/HBO1, and the common KAT6A/7 complex subunit BRPF1 associate with NUP98 FOs on chromatin and within condensates. MYST HATs are molecular dependencies in NUP98-rearranged (NUP98-r) leukemia, and genetic inactivation or pharmacologic inhibition of Kat6a and Kat7 impairs NUP98-r cell fitness. KAT6A/7 inhibition decreased global H3K23ac levels, displaced NUP98::HOXA9 from chromatin at the Meis1 locus, and led to myeloid cell differentiation. Additionally, KAT6A/7 inhibition decreased leukemic burden in multiple NUP98-r leukemia xenograft mouse models, synergized with Menin inhibitor treatment, and was efficacious in Menin inhibitor-resistant cells. In summary, we show that MYST family HATs are therapeutically actionable dependencies in NUP98-r AML.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-22T13:57:17.735529+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001076","title":"Exome sequencing for identifying point mutations driving M haemophilum susceptibility","description":"To understand non tuberculous Mycobacterial susceptibility","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-29T13:18:39.273004+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001077","title":"RNA-sequencing of ex situ stimulated donors blood cells","description":"Cells from whole blood stimulation assay were cryopreserved. The cryopreserved cells were thawed and subjected to RNA preparation. RNA obtained were subjected to for bulk sequencing.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-29T13:18:41.990098+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001078","title":"Pancreatic Cancer NGS WGS data","description":"Whole genome sequencing data for Pancreatic Cancer Samples exploring the tandem duplicator phenotype","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-20T14:59:58.209993+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001079","title":"Whole genome sequencing data of paediatric KMT2A-rearranged acute lymphoblastic leukemia","description":"Pediatric KMT2A-rearranged leukemia is an aggressive subtype of leukemia commonly seen in infants (less tha 1 year old) and young children. It involves rearrangements of the KMT2A gene (formerly MLL) on chromosome 11q23, resulting in fusion genes that drive uncontrolled cell growth. This subtype is most often found in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) and is associated with a poor prognosis. In infants, the 5-year event-free and overall survival rates are around 35–40%. Despite intensive chemotherapy, outcomes remain challenging, prompting ongoing research into targeted therapies and novel treatment strategies.\r\n","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-06T09:04:47.404845+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001080","title":"Changes in AXL and/or MITF melanoma subpopulations in patients receiving immunotherapy","description":"Our data demonstrate large interpatient variability and variable therapy-induced changes independent of the type of therapy. We identify the presence of previously described AXL+ and MITF+ subpopulations in metastatic tissues both at the mRNA level and in situ at the protein level, and demonstrate that MITF+ melanoma cells are significantly decreased upon immunotherapy, while AXL+ melanoma cell numbers are stable. MITF+ tumor cells showed the most significant inverse correlation with CD8+ T cells. Our patient cohort also shows that immunotherapy-induced changes in the abundance of AXL+ or MITF+ tumor cells did not correlate with improved survival.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[11652950],"external_links":null,"is_released":true,"released_date":"2025-07-17T13:02:12.697037+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001081","title":"ERBB2/HER2 alterations in ctDNA and metachronous tissues of patients with metastatic urothelial cancer - Targeted","description":"Targeted sequencing data related to the publication titled \"ERBB2/HER2 alterations in ctDNA and metachronous tissues of patients with metastatic urothelial cancer.\" ERBB2 alterations, usually amplifications or activating mutations, are seen in up to 20% of urothelial carcinoma and can be targeted by monoclonal antibodies, small molecule inhibitors, and most recently, antibody-drug conjugates. Here, we perform targeted and whole-genome sequencing of cell-free DNA and archival FFPE of mUC with and without ERBB2 alterations to identify unique genomic and clinical features of ERBB2-altered cancers, accompanied by IHC, FISH, and detailed clinical outcomes. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-25T14:45:06.810446+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001082","title":"ERBB2/HER2 alterations in ctDNA and metachronous tissues of patients with metastatic urothelial cancer - WGS","description":"Whole genome sequencing data related to the publication \"ERBB2/HER2 alterations in ctDNA and metachronous tissues of patients with metastatic urothelial cancer.\" ERBB2 alterations, usually amplifications or activating mutations, are seen in up to 20% of urothelial carcinoma and can be targeted by monoclonal antibodies, small molecule inhibitors, and most recently, antibody-drug conjugates. Here, we perform targeted and whole-genome sequencing of cell-free DNA and archival FFPE of mUC with and without ERBB2 alterations to identify unique genomic and clinical features of ERBB2-altered cancers, accompanied by IHC, FISH, and detailed clinical outcomes. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-25T14:45:05.409184+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001083","title":"Integrated drug screening and molecular profiling in pediatric AML","description":"This study aims at identifiying functional-genomic predictors of patient risk in pediatric AML by performing image-based drug response profiling and comprehensive molecular profiling on primary pediatric AML samples","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-18T12:00:12.193473+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001084","title":"The cellular state space of AML unveils novel NPM1 subtypes with distinct clinical outcomes and immune evasion properties","description":"Acute myeloid leukemia (AML) is a genetically and cellularly heterogeneous disease. We characterized 120 AMLs using bulk genomic and transcriptomic analyses (WES, MP-WGS, RNA-seq), and single-cell RNA sequencing (scRNA-seq). Our results reveal an extensive cellular heterogeneity that distorts the bulk transcriptomic profiles. Notably, NPM1 mutated AML could be stratified into two novel, clinically relevant classes (NPM1class I and NPM1class II).","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-30T16:32:25.113059+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001085","title":"Aberrant expression of SLAMF6 constitutes a targetable immune escape mechanism in acute myeloid leukemia","description":"In this study, we demonstrate that aberrant expression of SLAMF6 on acute myeloid leukemia (AML) cells serves as a novel immune escape mechanism that can be inhibited by antibodies against the SLAMF6 dimerization site. This constitutes a novel mechanism of checkpoint inhibition, which paves the way for immunotherapy in AML and other SLAMF6-expressing cancers. This study utilizes single cell sequencing data from the AML cell line HNT-34 co-cultured with normal T cells, with and without antibody targeting SLAMF6, as well as single cell data of 38 primary AML samples.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-06-30T16:32:25.226373+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001086","title":"RNaseq of mantle cell lymphoma patient samples","description":"This study presents bulk RNA sequencing data from 78 clinical mantle cell lymphoma (MCL) samples. Following rigorous quality control and batch effect correction to account for sample type and redundancy, 62 samples from 59 patients were included in the final analysis. The transcriptomic profiles capture the molecular diversity across both solid and liquid tumor contexts and support investigations into the phenotypic plasticity and metabolic states of drug-tolerant persister (DTP) cells.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001087","title":"RNAseq of  MCL cell lines","description":"This study profiles the transcriptomic response of the Mino-VEN-R and Jeko-BTK-R mantle cell lymphoma (MCL) cell lines to pirtobrutinib (PBN) treatment using bulk RNA sequencing. Mino-VEN-R models drug-tolerant persister (DTP) cells that arise during exposure to non-covalent BTK inhibitors. Building on our recent findings that DTP cells undergo metabolic and phenotypic state transitions governed by TCA cycle reprogramming, this dataset aims to capture gene expression changes associated with treatment-induced plasticity. The results contribute to a broader multi-omic framework exploring mechanisms of resistance and therapeutic vulnerability in MCL.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001088","title":"WES of Mino-VEN-R Mantle Cell Lymphoma Cells","description":"This project investigates the genetic basis of therapy resistance in mantle cell lymphoma (MCL) using whole exome sequencing (WES) of the Mino_VEN_R cell line, a model of resistance to pirtobrutinib, a non-covalent BTK inhibitor. Our study suggested that drug-tolerant persister (DTP) cells evade therapy through metabolic and phenotypic reprogramming. By analyzing the exome profile of resistant cells, this study aims to identify mutations associated with treatment escape and cellular plasticity. The findings will contribute to a better understanding of resistance mechanisms and support the development of more effective therapeutic strategies.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001089","title":"RNAseq of  MCL cell lines","description":"This study provides bulk RNA sequencing data from Mino and Jeko-1 mantle cell lymphoma (MCL) cell lines treated with CDK9 inhibitors, including the novel compound YX0798. CDK9 is a key regulator of RNA polymerase II–mediated transcription, and its inhibition disrupts transcriptional programs critical for tumor survival. The dataset captures transcriptomic changes associated with CDK9 inhibition, including downregulation of oncogenic drivers such as MYC and MCL-1. These data support mechanistic studies of transcriptional reprogramming and therapeutic vulnerability in aggressive MCL.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001090","title":"Metagenomic analysis of encephalitis with unknown origin in a single center retrospective study","description":"Cerebrospinal fluid samples from well-characterized patients (n=17) diagnosed with encephalitis of unknown origin according to Swedish national guidelines were sequenced using mNGS using the Ion Torrent platform and analyzed using bioinformatic platforms. Samples from patients with known viral CNS infections (HSV-2 meningitis (n=4), VZV CNS infections (n=3), enterovirus meningitis (n=2), JCV CNS infection (n=2) were used as controls for the methodology (n=11).","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001091","title":"COMPASS Next Generation Sequencing WGS data","description":"Whole genome sequencing data for Pancreatic Cancer Samples from the COMPASS clinical trial","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-28T16:35:36.115078+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001092","title":"Germline Pathogenic Variants in Homologous Recombination Pathway Genes are Frequent In Pancreatobiliary Ampullary Carcinoma","description":"Ampullary carcinoma is a rare type of cancer arising from the ampulla of Vater, which is classified into subtypes depending on the histologic appearance and epithelium of origin (pancreatobiliary and intestinal). Pancreatobiliary carcinomas are considered more aggressive and confer worse prognosis compared to the intestinal subtype [PMID: 18547417]. The two subtypes, however, appear not to have significant differences with respect to molecular profiles [PMID: 27488532, 32914025]. The contribution of germline variants to ampullary carcinoma has yet to be determined, given the rarity of this tumor type.  Studies of small cohorts of ampullary carcinomas have found isolated mutations in some cancer susceptibility genes, but no causative role has been established. [PMID: 30620386].  Therefore, no guidelines for whether genetic testing should be performed in individuals with ampullary carcinoma are currently available. In the MKSCC 12-245 part C cohort, we have now accrued a large cohort of 103 individuals with ampullary carcinoma whose blood and tumor DNA have been profiled with MSK-IMPACT, which will enable us determine the prevalence of germline pathogenic variants affecting cancer susceptibility genes in individuals with ampullary carcinoma and to use tumor genomic data to establish a causal role for these germline variants in tumor development.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001093","title":"ucfDNA workflows for molecular profiling of malignant disease","description":"\r\n\r\nUrinary cell-free DNA (ucfDNA) is a promising liquid biopsy analyte obtained by a non-invasive sampling method, particularly valuable in urological cancers due to the proximity of biofluids to the tumor site. However, extremely high fragmentation and low abundance of ucfDNA pose significant analytical challenges. Improper handling and storage can severely affect ucfDNA quality, necessitating optimized pre-analytical workflows for clinical applications. We evaluated multiple pre-analytical workflows, including urine stabilization approaches against unstabilized urine samples. Our results demonstrated that without stabilization, ucfDNA degraded rapidly and minimal quantities remaining after 72 hours. In contrast, urine stabilization preserved ucfDNA integrity, enabling successful downstream analyses, including digital PCR and next-generation sequencing, for mutation detection in cancer-related genes and genome wide copy number profiling. These findings underscore the critical role of stabilization for a reliable ucfDNA analysis and highlight its potential in molecular diagnostics as a complementary tool to plasma-based liquid biopsies. \r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-08T08:54:33.835974+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001094","title":"Spontaneously differentiatiated iPSCs to EBs","description":"SUM-seq data (single-cell chromatin accessibility and gene expression) for spontaneously differentiatiated iPSCs. This data is the representative data in the Nature Protocols publication.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-29T10:22:39.290628+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001095","title":"Transcriptome of periadrenal and subcutaneous fat in patients with hyperaldosteronism in comparison to patients with non-functional adenomas","description":"This study analyzed subcutaneous fat (SCF) and periadrenal fat (PAF) from patients with aldosterone-producing adenomas (APAs) and, as controls, non-functional adrenal adenomas (NFA) (SCF, n = 7; PAF, n = 5). ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-06T13:09:43.829022+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001096","title":"Whole Exome sequencing of Baseline biopsies","description":"Whole exome sequencing of BAseline CHC-noHCC and CHC-HCC biopsies.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-04T16:02:31.339366+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001097","title":"Baseline CHC transcriptomes","description":"RNA sequencing of Baseline CHC-noHCC and CHC-HCC samples.\r\nSnap frozen biopsies were crushed in liquid nitrogen. Total RNA was extracted using RNA MiniPrep Plus kit (Zymo Research) according to the manufacturer’s instructions. RNA sequencing of baseline CHC samples was done in paired-end mode on an Illumina HiSeq 2500 with 101 cycles. RNA-Seq was performed at the Department of Biosystems Science and Engineering ETH Zurich, D-BSSE in Basel. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-04T16:02:31.339366+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001098","title":"Normal livers, Matched non-tumor follow-up and HCV liver biopsy transcriptomes","description":"We compared CHC biopsies (Baseline) with normal livers to identify HCV induced transcriptional changes. At the time of HCC diagnosis in the CHC-HCC group, we collected matched non-tumor liver biopsies. Additionally we acquired liver biopsies from patients not included in the study with an active HCV infection for risk score prediction.\r\nSnap frozen biopsies were crushed in liquid nitrogen. Total RNA was extracted using the ZR-Duet DNA and RNA MiniPrep Plus kit (Zymo Research) according to the manufacturer’s instructions. RNA sequencing was done in single-end mode on an Illumina HiSeq 2500 with 101 or 51 cycles. RNA-Seq and WES were performed at the Department of Biosystems Science and Engineering ETH Zurich, D-BSSE in Basel. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-04T16:02:31.339366+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001099","title":" Dopaminergic neuron differentiation of human embryonic stem cells","description":"2 replicates of dopaminergic neuron differentiation of human embryonic stem cells from timepoints day 17 and day 28, performed with 10X Genomics single cell RNA-seq. Part of the Ásgrimsdottir et al. (Arenas Lab).","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-07T14:56:58.153685+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001100","title":"Whole genome sequencing data of relapsed paediatric KMT2A-rearranged acute lymphoblastic leukemia","description":"Whole genome sequencing data of relapsed KMT2A-rearranged leukemia. Dataset includes bam-file of released case. Diagnostic (ALLT-375D) and remission (ALLT-375R) samples can be found with EGA ID: EGAD50000001568. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-06T09:05:02.461532+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001101","title":"Repertoire and clinical hierarchy of AR locus alterations in castration-resistant prostate cancer","description":"Somatic alterations to the androgen receptor (AR) gene are pivotal drivers of treatment resistance in metastatic castration-resistant prostate cancer (mCRPC), but their prevalence, clinical impact, and etiology remain incompletely understood. Here, we analyzed 3399 plasma cell-free DNA samples and 1988 leukocyte DNA samples from 1995 metastatic prostate cancer patients with matched clinical data and extensive AR locus coverage.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-19T15:18:37.587248+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001102","title":"Development and validation of multivariate predictors of primary endocrine resistance to tamoxifen and aromatase inhibitors in luminal breast cancer reveal drug-specific differences ","description":"Background: Endocrine therapy is highly effective in blocking the estrogen receptor pathway in HR+/HER2- early breast cancer (EBC). However, up to 40% of patients experience relapse during or after adjuvant endocrine therapy. Here, we investigate molecular mechanisms associated with primary resistance to endocrine therapy and develop predictive models.\r\nResults: TP53 mutations were prominently associated with primary resistance to both tamoxifen (TAM) and aromatase inhibitors (AI), with AI non-responders exhibiting resistance in up to 32% of cases. Additionally, we identified distinct DNA methylation patterns in TAM and AI non-responders, with TAM non-responders showing global DNA methylation loss, associated with KRAS signaling, apical junctions and epithelial-mesenchymal transition (EMT). Conversely, we observed methylation gain in AI non-responders affecting developmental transcription factors, hypoxia and estrogen signaling. TAM or AI resistance was associated with increased methylation-inferred proportions of immune cells and decreased proportions of endothelial cells. Based on these findings and patient age, we developed the Predictive Endocrine ResistanCe Index (PERCI). PERCI stratified NR and R cases in both treatment groups and cohorts with high accuracy (ROC AUC TAM discovery 93.9%, validation 83%; AI discovery 98.6%, validation 76.9%). A simplified PERCI efficiently predicted progression-free survival in the TCGA-BRCA sub-cohort (Kaplan-Meier log-rank p-value = 0.03 between low and high PERCI groups).\r\nConclusions: We identified genomic and epigenomic features associated with primary resistance to TMA and AI. By combining information on genomic alterations, patient age, differential methylation and tumor microenvironment (TME) composition, we developed PERCI TAM and PERCI AI as novel predictors of primary resistance, with potential additional prognostic value. Applying PERCI in a clinical setting may allow patient-specific drug selection to overcome resistance.","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-18T12:02:56.247583+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001103","title":"Neuroblastoma Smart-Seq2 Single Nuclei Sequencing Data","description":"Heterogeneity of tumors, including the presence of resistant clones, represents a great challenge for high-risk neuroblastoma (NB). Currently, there are no treatments that address cancer heterogeneity. Classification of bulk tumors and corresponding predictions are poor and too general. Understanding heterogeneity will provide critical insight for the development of targeted therapeutic strategies. \r\nIn this study, we collected 10 human neuroblastoma tumor samples and performed whole-transcriptome profiling at single-nucleus resolution using SMART-Seq2 technology. This approach enables comprehensive characterization of transcriptional diversity within individual tumors, allowing us to identify distinct cellular subpopulations. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-18T14:35:02.282402+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001104","title":"RNA seq of intestinal biopsies and blood cells from patients with celiac disease and controls","description":"This study presents RNA sequenced from several intestinal phenotypes such as from patients with damaged intestinal mucosa as well as from those without a damaged intestine but still an autoantibody response to tissue transglutaminase (“potential celiac disease”) or those with treated celiac disease. By combining phenotypes in a much larger number of tissue samples from both peripheral blood and mucosal biopsies, we found highly differentially expressed genes, but also identify genes involved in controlling and triggering celiac disease associated changes.\r\n\r\nThis study identifies molecular mechanisms involved in celiac disease and new possible targets for treatment and for identification of individuals at risk.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-07T11:57:23.788153+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001105","title":"Genomic sequencing data for PNG15 and PNG16","description":"This study includes both long- and short-read sequencing data for PNG15 and PNG16 as well as their phased haplotype assemblies.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-02T14:16:37.726544+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001106","title":"Epigenetic profiling of primary human thymocyte subsets","description":"Dynamic changes of the DNA methylation (DNAmeth) landscape drive differentiation of mature T lymphocytes. However, the role of DNAmeth-mediated regulation in thymocyte development remains unclear. Thus, we generated genome-wide DNAmeth and transcriptomic profiles of eight defined, ex vivo isolated primary human thymocyte subsets, to assess the epigenetic remodling taking place during human thymic T cell development. The generated data may also serve as a reference for the analysis of T cell-based inborn errors of immunity or for quality control purposes of in vitro generated T cell populations. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-14T12:01:46.962641+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001107","title":"Impact of DIS3 Aso on BCR repertoir in human buffy coat purified B-Cells","description":"The aim is to identify difference in the BCR of Aso DIS3 treated cells compared to Control Aso. Using extracted DNA from human B-cells ","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-10T17:00:56.237308+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001108","title":"DHODH is a synthetic-lethal vulnerability in BCOR-deficient acute myeloid leukemia","description":"Acute Myeloid Leukemia (AML) remains challenging to treat, especially in cases with mutations in the BCL-6 co-\r\nrepressor (BCOR), which are associated with poor prognosis and chemo-resistance. In this study, we reveal a\r\nsynthetic lethal interaction between BCOR and dihydroorotate dehydrogenase (DHODH). We demonstrate that\r\nBCOR-deficient cells have a heightened sensitivity to DHODH inhibitors such as brequinar and leflunomide, that\r\nare already in clinical use. We confirm that DHODH inhibition selectively induces cell death in BCOR-mutant\r\ncells in multiple cellular models, in malignant and non-malignant cells, through chemical and genetic\r\nmanipulation. Interestingly, we find that the dependency on DHODH does not stem from its role in de novo\r\npyrimidine biosynthesis disruption. Rather, DHODH’s role in the electron transport chain, essential for mitigating\r\nreactive oxygen species, may be the physiological vulnerability that pushes BCOR-mutant cells toward cell death\r\nwhen DHODH is inhibited. DHODH inhibitors could be repurposed as targeted therapies for BCOR-mutant\r\ntumors, offering a promising strategy for precision medicine in AML and other cancers.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-10T13:05:46.541627+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001109","title":"Transcriptomic analysis of B-cell acute lymphoblastic leukaemia (B-ALL) patients treated on the ALL09 clinical trial","description":"This study provides comprehensive transcriptomic analysis of adolescent and young adult (AYA) patients treated on the Australasian Leukaemia and Lymphoma Group (ALLG) ALL09 clinical trial (ACTRN12618001734257). The ALL09 clinical trial is a Phase II single arm study to assess whether substitution of blinatumomab for conventional multi-agent chemotherapy in phase 2 induction leads to improved minimal residual disease negativity rates when compared to the historical AYA ALL trial cohort. Patients treated on this trial were aged 15-40 years, demonstrated morphological diagnosis of CD19 positive B-lineage acute lymphoblastic leukaemia (B-ALL), and were negative for Philadelphia chromosome-positive disease. Transcriptomic sequencing was performed as a correlative study to determine assess patients’ genomic subtypes and enable comparison of clinical outcome in blinatumomab treated patients.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-20T14:56:11.73958+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001110","title":"Predicting trajectories of acute illness using RNA velocity of whole blood - PERFORM Slovenian samples","description":"Transcriptomic analyses reveal the status of cells, tissues, or organisms, across states of health and disease. RNA velocity adds a temporal dimension to single cell analyses, predicting future transcriptomic and phenotypic states, based on current spliced and unspliced mRNA of each cell. We hypothesized that RNA velocity could be adapted to predict future clinical status of individuals with acute illness using their whole-blood transcriptome. We developed a method for quantitative prediction of transitions in clinical state from a single time-point sample, which we call VeloCD. This predicted transcriptomic trajectories and future infection status in influenza A and SARS-CoV-2 human challenge studies. In HIV-TB coinfected individuals, it predicted the onset of immune reconstitution inflammatory syndrome. In a multinational observational study of acutely unwell febrile children, VeloCD predicted those with greatest medical care requirements. Our results demonstrate a novel application of RNA velocity to predict the trajectory of acute illness.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001111","title":"RNA-seq analysis of midbrain dopaminergic neurons following ZFHX4 knockdown.","description":"We performed RNA-seq analysis on midbrain dopaminergic neurons derived from induced pluripotent stem cells following lentiviral-mediated knockdown of the transcription factor ZFHX4. Transcriptomic analysis enabled the identification of potential ZFHX4 target genes. Enrichment analysis of the differentially expressed genes was conducted to assess the biological pathways regulated by ZFHX4.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-29T13:30:19.636125+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001112","title":"CUT&Tag sequencing of ZFHX4 and H3K27ac in midbrain dopaminergic neurons.","description":"CUT&Tag sequencing of the transcription factor ZFHX4 and the histone mark H3K27ac was performed in midbrain dopaminergic neurons (mDANs) derived from induced pluripotent stem cells. This epigenomic approach enabled the identification of ZFHX4 binding sites in this specific cellular context. Comparing the CUT&Tag profiles of ZFHX4 and H3K27ac provided insights into epigenetic landscapes in mDANs and revealed whether ZFHX4 exhibits patterns similar to the active transcription mark H3K27ac. Finally, enrichment analysis of the identified peaks highlighted potential primary targets of ZFHX4 in mDANs.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-29T13:30:19.636125+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001113","title":"A single-chain derivative of the integrin β1-activating TS2/16 antibody potentiates organoid growth in Matrigel and Collagen hydrogels.","description":"Culturing epithelial organoids from Adult Stem Cells (ASCs) requires interaction of their β1-integrins with extracellular matrix (ECM) components such as laminin or collagen. Matrigel and BME® (extracts from Engelbreth-Holm-Swarm tumor cells grown in the mouse abdomen) are a popular source of ECM proteins. Yet, these preparations are costly and subject to batch-to-batch variation due to animal-derived contaminations. Here, we describe a single chain version (scFv) of antibody TS2/16, allosterically activating integrin β1 function in organoids. Addition of 5 nM of monomeric scFv to organoid medium results in up to 5-fold higher yields of organoids in Matrigel/BME®. In addition, scTS2/16 generates 6-7-fold higher yields of intestinal organoids in collagen-I hydrogel, when grown both in 3D and in 2D. Collagen is well-defined, available at clinical grade, and in combination with scTS2/16, will enable the clinical use of gastrointestinal organoids.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-10T13:05:43.770344+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001114","title":"LongVar low-coverage data","description":"This dataset includes sequencing data from participants of the LongVar study. Specifically, it comprises low-coverage whole genome sequencing (WGS) data which was derived from cell-free DNA from blood samples. These data were generated to compare imputation accuracy. 133 individuals agreed to share their data, and are healthy volunteers.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-17T10:07:55.15689+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001115","title":"Methylome sequencing by cfRRBS","description":"The methylation profile of circulating cell-free DNA (cfDNA) is of great interest as a liquid biopsy for the detection and monitoring of cancer and other pathologies. Here we introduce ‘circulating cell-free DNA reduced representation bisulfite sequencing’ (cf-RRBS), enabling the use of highly effective RRBS on highly fragmented plasma cfDNA as well as on FFPE-archived cancer tissues. The method enriches the CpG-rich RRBS target regions by enzymatic degradation of all off-target DNA rather than by targeted capture, in contrast to previous methods. Critical steps are fully enzymatic in a single-tube, making it rapid, cost-effective, robust and easily implemented on a liquid-handling station for high-throughput sample preparation. We benchmark cf-RRBS results to those obtained by previous more complex methods and exemplify its use for accurate non-invasive subtyping of lung cancer, a frequent onco-pathology task. cf-RRBS enables any molecular pathology lab to tap into the cfDNA methylome, only making use of off-the-shelf reagents and open-source data analysis tools.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001116","title":"Nala TAS-LRS PGx Study","description":"Pharmacogenomics (PGx) testing improves medication safety and efficacy by identifying genetic variants that affect drug response. However, current technologies often fail to resolve complex loci, detect structural variants, or phase alleles accurately. Here, we present an end-to-end PGx workflow based on Targeted Adaptive Sampling-Long Read Sequencing (TAS-LRS), integrating a streamlined laboratory protocol with a bioinformatics pipeline that includes a novel CYP2D6 caller. Using 1,000 ng of DNA and three-sample multiplexing on a single PromethION flow cell, the assay achieves consistent on-target (25x) and off-target (3x) coverage, enabling accurate, haplotype-resolved testing of 35 pharmacogenes alongside genome-wide genotyping from off-target reads. We further developed the workflow into a clinically ready service and validated its performance across 17 reference and clinical samples. The assay demonstrated high concordance for small variants (99.9%) and structural variants (>95%), with phased diplotypes and metabolizer phenotypes reaching 97.7% and 98.0% concordance, respectively. Improved calls were observed in 12 genes due to enhanced genotyping, phasing, or novel allele detection. In addition, off-target reads supported accurate genome-wide imputation, comparable to short-read sequencing and superior to microarrays. These results establish the feasibility of long-read sequencing for clinical PGx testing and position TAS-LRS as a scalable solution combining both targeted and genome-wide utility.","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-18T13:41:52.75512+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001117","title":"scRNA-seq data of FOXN1heterozygous patients and cord blood","description":"Single cell sequencing was performed from sorted CD45+ lymphocytes from two FOXN1het patients and one cord blood sample from frozen cryopreserved samples. Each sorted population was labelled individually via multiplexing with subsequent Abseq staining before pooling and conducting the BD Rhapsody pipeline.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001118","title":"Integrated transcriptomics to study MS lesion heterogeneity","description":"In this study, we address the heterogeneity of cells and their (altered) interactions in different MS lesion types with single-nucleus RNA sequencing and integrate these findings with spatial transcriptomics data to localise changes in cell states that might be involved in lesion evolution. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001119","title":"Whole-exome variant calling of individuals from the study of sepsis and acute distress respiratory syndrome in Spain","description":"Research study of genetic susceptibility in sepsis and acute distress respiratory syndrome (ARDS). ARDS is a lethal condition, often derived from sepsis, lacking effective targeted treatments. Growing evidence indicates that the genetic component significantly influences susceptibility and severity of ARDS. We used whole-exome sequencing data in case-control studies to characterize genetic factors associated with an increase of ARDS risk.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-28T14:36:33.641037+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001120","title":"p200503_fn1","description":"RNA-Sequencing data of tumor spheroids (HT-29) incubated with medium conditioned by Fusobacterium nucleatum treated CAFs (patient derived CAF20 and CAF32 as well as the CAF05 cell line).","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-17T10:20:39.05261+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001121","title":"p200503_fn2","description":"RNA-Sequencing data of Fusobacterium nucleatum (Fna 71) treated CRC patient derived (CAF180, CAF181) and CAF05 cancer associated fibroblasts (CAFs).","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-17T10:20:39.05261+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001122","title":"Spatial Dynamics of the Developing Human Heart","description":"Heart development relies on a topologically defined interplay between diverse cardiac cells. We finely curated spatial and single-cell measurements with high-resolution imaging-based transcriptomics validation to explore spatial dynamics during early human cardiogenesis. Analyzing almost 80,000 individual cells and 70,000 spatially barcoded tissue regions between the 5.5th and 14th postconceptional weeks, we identified 31 coarse- and 72 fine-grained cell states and mapped them to highly resolved cardiac cellular niches. We provide novel insight into the development of the cardiac pacemaker-conduction system, heart valves, and atrial septum, and decipher heterogeneity of the hitherto elusive cardiac fibroblast population. Furthermore, we describe the formation of the cardiac autonomic innervation and present the first spatial account of chromaffin cells in the fetal human heart. Our study, supported by an open-access, spatially centric interactive viewer, delineates the cellular and molecular architecture of the developing heart, offering links to genetic causes of heart disease.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-14T11:19:43.000705+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001123","title":"CLUSTER consortium RNAseq CD19 B cell dataset of UK JIA patients.","description":"This study examines B cell transcriptomic profiles in Juvenile Idiopathic Arthritis (JIA) patients to investigate molecular mechanisms underlying disease heterogeneity. CD19+ B cells were isolated from peripheral blood samples and subjected to RNA sequencing to characterise gene expression patterns. The dataset includes patients with documented uveitis status to enable investigation of B cell contributions to the common JIA comorbidity.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-21T10:26:55.936533+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001124","title":"Evaluation of an ex vivo immunotherapy platform using EV-primed immune cells and patient-derived glioblastoma spheroids","description":"This study presents an ex vivo co-culture system integrating glioblastoma stem-like cells (GSCs) and extracellular vesicle (EV)-primed peripheral immune cells to explore immunotherapeutic responses. EVs were derived from mock- or virus-infected GSCs to modulate immune activity. scRNA-seq was used to assess immune cell activation, functional states, and tumor–immune interactions. The platform enables high-resolution analysis of immune dynamics and EV-mediated immunomodulation in glioblastoma.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001125","title":"RNAseq profile of monomorphic epitheliotropic intestinal T-cell lymphoma and enteropathy associated T-cell lymphoma","description":"Background : Enteropathy-associated T-cell lymphoma (EATL) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) are aggressive malignancies with limited treatment options and poor prognosis. Our research on MEITL has uncovered its genetic portrait including hallmark SEDT2 mutations, expanded its pathological spectrum, and identified molecular biomarkers influencing patients’ outcome. In this study, we aimed to establish and clarify the similar and diverging features of EATL.  \r\nMethods : A large combined cohort of patients with EATL (n=30) and MEITL (n=52) was assembled and tumor samples were used for whole-exome and RNA sequencing profiling.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-04T08:50:15.344732+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001126","title":"Whole Exome Sequencing of monomorphic epitheliotropic intestinal T-cell lymphoma and enteropathy associated T-cell lymphoma","description":"Background : Enteropathy-associated T-cell lymphoma (EATL) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) are aggressive malignancies with limited treatment options and poor prognosis. Our research on MEITL has uncovered its genetic portrait including hallmark SEDT2 mutations, expanded its pathological spectrum, and identified molecular biomarkers influencing patients’ outcome. In this study, we aimed to establish and clarify the similar and diverging features of EATL.  \r\nMethods : A large combined cohort of patients with EATL (n=30) and MEITL (n=52) was assembled and tumor samples were used for whole-exome and RNA sequencing profiling.\r\n","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-04T08:50:12.314692+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001127","title":"Single-cell profiling reveals monocyte mitochondrial dysfunction in patients with cirrhosis progressing to acute-on-chronic liver failure","description":"We performed single-cell RNA-seq and CITE-seq in PBMC samples derived from patients with acutely decompensated cirrhosis at risk of developing ACLF, as well as from Healthy Donors. We identified a population of monocytes associated with disease progression. We also explored the presence of this cell population in blood samples by bulk RNA-sequencing.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-31T12:00:30.758765+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001128","title":"TGF-β Signaling Promotes a Conserved Gene Signature in Neuron-Associated Macrophages in the Human Gut","description":"Human colon mucosa, submucosa and muscularis resection tissues have been subjected to scRNA-seq. The goal is to study, transcriptionally, the difference between the layers of the human gut in healthy tissue. CD45 cells have been studied with a focus on the monocyte-marcophage compartment. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001129","title":"RIP-seq of SF3B4 binding RNA fragments","description":"There are 2 paired samples. The project aims to characterize SF3B4 binding RNA fragments within liver organoids to understand its role in splicing regulation","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-13T09:56:50.251287+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001130","title":"DNA sequencing of sgRNAs enriched from the CRISPR-Cas9 screened HCC organoids","description":"There are 12 samples. The project aims to find enriched or depleted sgRNAs to identify functional genes in HCC progression and lenvatinib resistance","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-13T09:56:50.251287+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001131","title":"Long-read and short-read RNA sequencing of human normal liver organoid with or without SF3B4 overexpression","description":"There are 2 matched short and long read RNA sequencing samples. The project aims to find alternative splicing events and resulting transcript isoforms modulated by SF3B4","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-13T09:56:50.251287+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001132","title":"germline pathogenic variants found in African patients of prostate cancer","description":"70 new blood samples added in this project","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-31T10:49:59.080433+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001133","title":"Single-cell RNAseq of air-liquid interface airway epithelial cells after IL-13 treatment, using cells isolated from healthy donors or severe asthma patients","description":"In asthma, chronic inflammation and airway remodeling profoundly alter the epithelial landscape, characterized by a decrease in multiciliated cells and a hyperplasia of mucus-secreting goblet cells. Current therapeutics primarily target the interplay between immune and epithelial cells to mitigate these effects. However, the epithelial-intrinsic mechanisms driving airway remodeling remain underexplored. \r\nTo identify molecular regulators of airway remodeling, we reconstructed airway epithelia using basal cells from healthy or severe asthma donors. Using single-cell RNA sequencing, we analyzed differential cellular and molecular features at baseline, following IL-13 or House Dust Mite (HDM) treatments and upon recovery.\r\nSingle-cell RNAseq was performed with 3’ 10X genomics. Some samples were multiplexed either with hashtag antibodies or CMO from 10X genomics. Some cell pools were demultiplexed using single nucleotide polymorphisms. \r\nThe dataset is composed of 122 samples with 199,606 cells: 52 samples from healthy donors and 70 samples from severe asthma patients. 87 samples were bronchial epithelial cultures, 35 were nasal epithelial cultures. 48 samples were done at timepoint 1 (day 8) and 74 samples at timepoint 2 (day 22). \t\r\n- 22 samples were treated with IL13 for timepoint 1 (IL13_1)\r\n- 22 samples were treated with IL13 for timepoint 2 (IL13_2)\r\n- 22 samples were washed-out after IL13 for timepoint 2 (ILRV_2)\r\n- 3 samples were treated with HDM for timepoint 1 (HDMM_1)\r\n- 6 samples were treated with HDM for timepoint 2 (HDMM_2)\r\n- 2 samples were washed-out after HDM for timepoint 2 (HDRV_2)\r\n- 23 samples were untreated for timepoint 1 (CTRL_1)\r\n- 22 samples were untreated for timepoint 2 (CTRL_2)\r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001134","title":"Genomic landscape of poorly differentiated thyroid carcinoma","description":"Poorly differentiated thyroid carcinoma (PDTC) is a rare and aggressive subtype of thyroid cancer with limited molecular characterization. This study aims to define the somatic mutational landscape of PDTC using whole-genome sequencing. Paired tumour and matched normal blood samples were collected from six patients undergoing surgery. The overarching goal is to identify recurrent mutations, structural variants, and other genomic alterations associated with tumour aggressiveness and poor clinical outcomes.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-18T12:05:41.352811+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001135","title":"Transcriptomic profiling of myeloid cells from secondary lymphoid organs (lymph nodes and tonsils) from lymphoma patients and controls.","description":"Despite their recognized impact on the pathogenesis and prognosis of B-cell lymphoma, tumor-associated macrophages (TAM) have not been extensively explored in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). We investigated mononuclear phagocyte (MNP) heterogeneity using single cell RNA sequencing (scRNAseq) in B-cell lymphoma lymph nodes compared to reactive secondary lymphoid organs (lymph nodes and tonsils). ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-25T14:59:00.604827+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001136","title":"Variant analysis on FFPE specimen from NSCLC patients (OCAPlus)","description":"This study assessed the presence of somatic variants via the Oncomine Comprehensive Panel Plus panel (ThermoFisher) for commonly mutated cancer genes and measure tumor mutational burden using next-generation sequencing. It was performed on genomic DNA from FFPE tissue of tumor resections. Mutations were used to draw OncoPrints and to assess TMB in relation with response metrics.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-31T13:28:16.662632+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001137","title":"T-cell receptor repertoire profiling (PBMC)","description":"This study assessed the TCR repertoire in peripheral blood from patients before, during and after neoadjuvant chemoimmunotherapy. TCR beta chain sequences in RNA from peripheral blood were amplified with the OncomineTM long read assay, templated and sequenced. TCR metrics such as clonality, evenness and diversity were assessed in relation with response metrics. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-31T13:28:16.662632+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001138","title":"T-cell receptor repertoire profiling (FFPE tissue)","description":"This study assessed the TCR repertoire in tumor tissue from NSCLC patients before, during and after neoadjuvant chemoimmunotherapy. TCR beta chain sequences in RNA from FFPE tissue were amplified with the OncomineTM short read assay, templated and sequenced. TCR metrics such as clonality, evenness and diversity were assessed in relation with response metrics. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-31T13:28:16.662632+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001139","title":"Variant analysis on FFPE specimen from NSCLC patients (FoundationOne CDx)","description":"This study assessed the presence of somatic variants via the FoundationOne CDx panel of commonly mutated cancer genes and measure tumor mutational burden using next-generation sequencing panels. It was performed on genomic DNA from FFPE tissue of tumor resections. Mutations were used to draw OncoPrints and to assess TMB in relation with response metrics. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-31T13:28:16.662632+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001140","title":"Targeted gene expression analysis on FFPE specimen from NSCLC patients","description":"This study measured the expression of a panel of over 300 cancer immunotherapy-relavant genes in tumors after neoadjuvant chemoimmunotherapy. It was performed on RNA from FFPE tumor tissue. Differential gene expression analysis was performed between patients achieving or not achieving an event-free survival of 12 months. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-31T13:28:16.662632+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001141","title":"Transposable Elements Shape Stemness in Normal and Leukemic Hematopoiesis","description":"Despite most acute myeloid leukemia (AML) patients achieving complete remission after induction chemotherapy, two-thirds will relapse with fatal disease within five years. AML is organized as a cellular hierarchy sustained by leukemia stem cells (LSC) at the apex, with LSC properties directly linked to tumor progression, therapy failure, and disease relapse 1–5. Despite the central role of LSC in poor patient outcomes, little is known about the genetic determinants driving their stemness properties. As LSCs share many functional and molecular properties with normal hematopoietic stem cells (HSC) 6, we investigated accessible chromatin unique across normal hematopoietic and cancer cell states and identified transposable elements (TEs) as genetic determinants of both primitive populations in comparison with their downstream mature progeny. A clinically-relevant TE chromatin accessibility-based LSCTE121 signature was developed that enabled patient classification based on survival outcomes. Through functional assays, primitive cell specific-TE subfamilies were found to serve as docking sites for stem cell-associated regulators of genome topology or lineage-specific transcription factors, including LYL1 in LSCs. Finally, using chromatin editing tools, we establish that chromatin accessibility at LTR12C elements in LSCs are necessary to maintain stemness properties. Our work identifies TEs as genetic drivers of primitive versus mature cell states, where distinct TE subfamilies account for stemness properties in normal versus leukemic hematopoietic stem cells.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-09T10:58:28.855967+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001142","title":"Adaptive Therapy Exploits Fitness Deficits in Chemotherapy-Resistant Ovarian Cancer to Achieve Long-Term Tumor Control Open Access","description":"Drug resistance results in poor outcomes for cancer patients. Adaptive therapy is a potential strategy to address drug resistance that exploits competitive interactions between sensitive and resistant subclones. Here, we showed that adapting carboplatin dose according to tumor response (adaptive therapy) significantly prolonged survival of murine ovarian cancer models compared to standard carboplatin dosing, without increasing mean daily drug dose or toxicity. Platinum resistant ovarian cancer cells exhibited diminished fitness when drug was absent in vitro and in vivo, which caused selective decline of resistant populations due to reduced proliferation and increased apoptosis. Conversely fitter, sensitive cells re-grew when drug was withdrawn. Using a bioinformatics pipeline that exploits copy number changes to quantify the emergence of treatment resistance, analysis of cell‐free DNA obtained longitudinally from ovarian cancer patients during treatment showed subclonal selection through therapy, and measurements of resistant population growth correlated strongly with disease burden. These preclinical findings pave the way for future clinical testing of personalized adaptive therapy regimens tailored to the evolution of carboplatin resistance in individual ovarian cancer patients.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[40299825],"external_links":null,"is_released":true,"released_date":"2025-10-13T15:57:34.204479+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001143","title":"Single nucleus and spatial transcriptomic characterization of prostate cancer versus normal controls","description":"10x Genomics Visium and Chromium platforms were used for spatial and single-nuclei RNA-sequencing, respectively. Cohort consisted of 8 prostate cancer patients (8 prostate cancer + 8 paired non-malignant control samples, fresh-frozen)","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-31T17:41:31.643072+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001144","title":"Sequencing data for Clinical Trial","description":"This study is a tri-institutional Phase 1/randomized Phase 2 trial, bevacizumab-naïve rHGA patients were randomized to either LITT (laser interstitial thermal therapy) plus pembrolizumab (LITT+PEM) or non-LITT surgery plus pembrolizumab (NLS+PEM). Randomization ceased after 21 patients when emerging data showed limited adjuvant ICI (immune checkpoint inhibitors) benefit, and the next 24 patients all received LITT+PEM. The goal of the trial is to use LITT, a minimally invasive cytoreductive approach, to prime these “cold” tumors for enhanced ICI response. \r\n\r\nrHGA= high-grade astrocytoma","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-30T16:19:31.225316+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001145","title":"The UVA-induced single-base mutational signature of CX5461 in human cells","description":"Drug-related UVA-induced photoreactions have been reported for several therapeutic compounds, including fluoroquinolones. CX5461 is a clinically relevant quinolone-derived anti-cancer small molecule with documented UVA-sensitising activity. Here we compared, by bulk and clonal whole genome sequencing (WGS) under light-protected conditions, the mutational signatures in human retinal pigment epithelial cells (RPE1) exposed to UVA, CX5461, or co-exposed to UVA and CX5461. Treatment with CX5461 or UVA alone resulted in a low SNV burden and background-like mutational profiles.  In contrast, bulk sequencing of human cells co-exposed to UVA and CX5461 had a markedly higher SNV burden characterized by T>A and T>C substitutions. Furthermore, single-cell clonal expansion and sequencing of CX5461 alone, UVA alone or CX5461+UVA treatments confirmed that the pattern was only observed when cells were exposed to both UVA and CX5461. The CX5461+UVA-associated SNV signature we report arises only when CX5461-treated cells are exposed to UVA, and is not observed when CX5461-treated cells are shielded from light. We do not observe strong single base mutagenic activity of CX5461 alone, under light protected conditions. Our data emphasise the need for appropriate controls and light-exposure precautions when studying base mutagenesis activity of known photosensitiser molecules.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-20T15:03:36.76981+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001146","title":"Multi-modal spatial characterization of tumor-immune microenvironments in diffuse large B-cell lymphoma  ","description":"We have leveraged spatial transcriptomics together with proteomic and genomic analysis to investigate the spatial immunology and pathobiology of DLBCL. We define distinct cellular niches that differ in frequency across tumors, related to both Epstein-Barr virus (EBV) infection status and the anatomical site of the tumor, and show that residence within different cellular niches is associated with divergent functional states of T-cells and tumor B-cells due to different patterns of cell-cell communication. This provides a framework for understanding stereotyped patterns of spatial organization in DLBCL and immunological interactions associated with heterogeneity in immune cell infiltration and function across patients.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-28T07:56:01.097467+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001147","title":"Transposable Elements Shape Stemness in Normal and Leukemic Hematopoiesis","description":"Despite most acute myeloid leukemia (AML) patients achieving complete remission after induction chemotherapy, two-thirds will relapse with fatal disease within five years. AML is organized as a cellular hierarchy sustained by leukemia stem cells (LSC) at the apex, with LSC properties directly linked to tumor progression, therapy failure, and disease relapse 1–5. Despite the central role of LSC in poor patient outcomes, little is known about the genetic determinants driving their stemness properties. As LSCs share many functional and molecular properties with normal hematopoietic stem cells (HSC) 6, we investigated accessible chromatin unique across normal hematopoietic and cancer cell states and identified transposable elements (TEs) as genetic determinants of both primitive populations in comparison with their downstream mature progeny. A clinically-relevant TE chromatin accessibility-based LSCTE121 signature was developed that enabled patient classification based on survival outcomes. Through functional assays, primitive cell specific-TE subfamilies were found to serve as docking sites for stem cell-associated regulators of genome topology or lineage-specific transcription factors, including LYL1 in LSCs. Finally, using chromatin editing tools, we establish that chromatin accessibility at LTR12C elements in LSCs are necessary to maintain stemness properties. Our work identifies TEs as genetic drivers of primitive versus mature cell states, where distinct TE subfamilies account for stemness properties in normal versus leukemic hematopoietic stem cells.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-09T10:59:35.021022+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001148","title":"Multimodal antigenic escape to GPRC5D-targeted T-cell engagers in multiple myeloma","description":"We analyzed the genome of plasma cells collected from bone marrow samples or plasmocytoma from patients prior to (when available) and progression on anti-GPRC5D T cell engagers.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-29T12:09:08.159629+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001149","title":"Study of biomarkers implicated in radio-immunotherapy response in metastatic cancer","description":"Immuno-radiotherapy may improve outcomes for patients with advanced solid tumors, although optimized combination modalities remain unclear. Here, we report the  analysis from the SABR-PDL1 (NCT02992912) trial that evaluated the PD-L1 inhibitor atezolizumab in combination with stereotactic body radiation therapy (SBRT) in patients with advanced cancer. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-29T19:11:56.505382+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001150","title":"Aging and viral evolution impair immunity against dominant pan-coronavirus-reactive T cell epitope","description":"In this project we have analysed gene expression and Tcell repertoires of CD40L+41bb+ and CD40L-41bb- Tcells from young and old donors after stimulation with the iCope peptide.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-01T14:10:20.881233+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001151","title":"Diverse transcriptomic and mutational patterns but limited functional pathway alterations in patient-derived SS cells","description":"We profile the whole-transcriptome of 7 patient-derived Sézary Syndrome (SS) cells to identify expression patterns, functional programs and expressed gene mutations that may provide clues on new therapeutic options for SS patients. The libraries were sequenced on NextSeq500 (Illumina) with a paired-end read length of 2x75bp.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-01T12:23:07.447177+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001152","title":"RNA Sequencing of Control and Myotonic Dystrophy Type 1 Cells During Myogenic Differentiation","description":"Immortalized control, patient-derived and CRISPR/Cas9-edited patient-derived myoblasts (known in the literature as C25, DM11, and DM11_1E6 cells, respectively) were grown confluent and were fused to myotubes in differentiation medium. Samples were collected at day -2 before initiation of differentiation (i.e. proliferation stage), at day 1 and at day 5 of differentiation in lysis buffer and stored at -70 degrees until all samples were collected.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-14T15:03:26.93995+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001153","title":"Heparan sulfate SULFatases ensure correct patterning of stem cell–derived midbrain dopaminergic neurons","description":"Midbrain dopaminergic (mDA) neuron loss underlies Parkinson’s disease (PD), making it critical to understand how mDA identity is established during development for cell replacement therapy. While intrinsic transcriptional programs and morphogen gradients driving mDA are known, the contribution of extracellular modulators remains less explored. Here, we show that the heparan sulfate (HS)–modifying enzymes SULF1 and SULF2 are essential for proper mDA neuron differentiation in vitro using CRISPR/Cas9-engineered human iPSCs, we demonstrate that SULF1/2 double knockout (DKO) cells. \r\n\r\n","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-10T10:35:55.368633+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001154","title":"Genome- and epigenome-driven evolutionary dynamics of tumour-immune coevolution within primary colorectal cancers","description":"This data includes targeting sequencing of the immunopeptidome from 94 samples, usually individual laser microdissected cancer glands, from 11 cases of colorectal cancer. The data were used to test for evidence of immunoediting (antigen depletion) in colorectal cancers. The full data description is provided in the original manuscript https://pmc.ncbi.nlm.nih.gov/articles/PMC10888923/.\r\nThe 11 colorectal cancers had been previously multiomic profiled with data described in the parts of this disposition.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[10888923],"external_links":null,"is_released":true,"released_date":"2025-10-09T16:31:40.50773+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001155","title":"HTAS of CD34+ HSPCs in relation to evaluating gene editing outcomes for CGD-causing variants in CYBA and CYBB","description":"High-throughput amplicon sequencing were performed on CD34+ hematopoietic stem and progenitor cells (HSPCs) derived from 4 healthy donors and one unaffected heterozygous carrier of a CYBB c.252G>A variant causing X-linked granulomatous disease. Targeted genome editing were performed in the HSPCs of CYBA and CYBB genes using CRISPR-Cas9 and recombinant AAV6. To assess gene editing outcomes in CD34+ HSPCs, the targeted loci were amplified from genomic DNA and sequenced with 150-bp paired-end reads on an Illumina iSeq 100 or MiniSeq. Editing rates were determined with CRISPResso2 in HDR mode using standard parameters. The dataaset here contains paired raw fastq files of each sample.","abstract":null,"study_type":"Synthetic Genomics","pubmed_ids":[40796771],"external_links":null,"is_released":true,"released_date":"2025-07-29T13:27:52.203693+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001156","title":"Single cell long read whole genome sequencing reveals somatic transposon activity in human brain","description":"The advent of single cell DNA sequencing revealed astonishing dynamics of genomic variability, but failed at characterizing smaller to mid size variants that on the germline level have a profound impact. In this work we discover novel dynamics in three brains utilizing single cell long-read sequencing. This provides key insights into the dynamic of the genomes of individual cells and further highlights brain specific activity of transposable elements.  ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-07-28T16:33:20.962587+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001157","title":"B Cell Receptor Repertoire Study From Individuals Resilient to Frontotemporal Dementia","description":"Individuals with resilience to disease often produce protective antibodies that confer this resilience. In this study we analysed the B cell receptor repertoire of 21 individuals resilient to Frontotemporal dementia (with C9orf72 or GRN mutations; non-symptomatic), 18 individuals with Frontotemporal dementia (with C9orf72 or GRN mutations and symptomatic diseases; defined as progressors) and 14 healthy controls to discover protective antibodies.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001158","title":"SCANDARE HNSCC","description":"Prospective biobanking study in SCANDARE HNSCC (Head and Neck Squamous Cell Carcinoma) patients aiming at better understand the link between the molecular alterations of the tumor itself, its microenvironment and immune response.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-01T12:21:14.293358+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001159","title":"APC-related multiple salivary gland lesions","description":"This study aims to investigate the genetic and molecular mechanisms underlying a novel phenotype of attenuated familial adenomatous polyposis (AFAP), where affected individuals develop multiple salivary gland tumours, including basal cell adenomas and adenocarcinomas.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001160","title":"The brain neurovascular epigenome and its association with dementia ","description":"Cerebral small vessel disease (SVD) is frequently comorbid with Alzheimer’s disease (AD) and vascular brain endothelial cells (BECs) are enriched for the expression of genes associated with AD genetic risk. However, the gene regulatory landscapes of neurovascular cells and their intersection with genetic risk for disease remains unexplored. Here we have generated gene regulomes for human BECs, mural cells and other brain cell types to show that AD heritability is primarily immune-related and that it shows modest enrichment in BECs. By contrast, genetic risk for SVD is enriched across cells of the neurovascular unit, including astrocytes. Enhancer-to-gene interactomes implicate amyloid processes in both AD and SVD, though the risk genes are mostly distinct for the two disorders. Motifs for putative partners of lineage transcription factors in microglia and BECs were enriched for AD and SVD variants at genes linked to disease pathways. Gene prioritization and enrichment analyses further identified potential repurposable drugs for AD. Our findings highlight novel regulatory mechanisms and therapeutic targets within the neurovascular system.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-23T17:05:09.16476+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001161","title":"SCANDARE ovarian","description":"Prospective biobanking study in ovarian cancer patients aiming at better understand the link between the molecular alterations of the tumor itself, its microenvironment and immune response.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-01T12:21:19.379261+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001162","title":"NFE2 and PF4 as Translational Biomarkers for BET Inhibition-Induced Thrombocytopenia in Preclinical and Clinical Studies","description":"Blood samples from patients treated with BMS-986158 were investigated for association with thrombocytopenia following BET inhibition. Hypotheses of translational biomarkers for early prediction of thrombocytopenia associated with BET inhibition were explored.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-15T15:10:08.574478+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001163","title":"WES-based association study of cefaclor-induced anaphylaxis","description":"This study investigates the genetic factors associated with cefaclor-induced anaphylaxis using whole-exome sequencing (WES). ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001164","title":"BIOMEDE : genomic data analysis from clinical trial","description":"Genomics landscapte of DIPG","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-21T15:16:49.041224+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001165","title":"Translational analyses from a phase II study of pembrolizumab and epigenetic modification with azacitidine in platinum-resistant epithelial ovarian cancer","description":"Epigenetic modulators may sensitize platinum-resistant ovarian cancer (PROC) to immune checkpoint inhibition by reprogramming the tumor microenvironment. We report clinical and translational findings from a phase II non-randomized study of pembrolizumab and oral azacytidine in 34 women with PROC (NCT02900560). The effect of combined epigenetic and immunotherapy was evaluated by transcriptomic analyses of serially biopsied tumors. Differential gene expression analyses revealed an upregulation of inflammatory and cytolytic genes and co-inhibitory checkpoints 6 weeks on-therapy. Upregulation of interferon signaling, antigen presentation and immune cell adhesion and migration gene sets was prominent on-therapy, together with an increased density of CD8+ T -cells. Patients with a CA-125 and/or clinical response showed an enrichment of adaptive and conserved immune response gene sets on-therapy. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-29T15:54:49.773936+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001166","title":"Study assessing the efficacy and safety of durvalumab plus olaparib plus fulvestrant in selected metastatic or locally advanced ER-positive, HER2-negative breast cancer patients.","description":"This study aims to evaluate the efficacy of the combination of olaparib, durvalumab, and fulvestrant for the treatment of patients with ER-positive, HER2-negative, locally advanced or metastatic breast cancer with BRCA gene alterations or alterations of genes involved in HRR or MSI status, in terms of the progression-free survival rate (PFSR) at 24 weeks.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-20T15:01:42.943554+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001167","title":"Allogeneic induced pluripotent stem (iPS) cell-derived cartilage transplantation for articular cartilage damage in knee joints: a phase I, first-in-human study","description":"Damaged articular cartilage seldom heals due to a limited capacity for self-repair, frequently leading to osteoarthritis. Regenerative interventions are expected to heal the damage. We have recently established a method to produce cartilage from induced pluripotent stem cells (iPSCs) in a clinically applicable process. The primary aim of this study was to evaluate the safety including tumorigenesis and the subsequence efficacy of allogeneic iPSC-derived cartilage transplantation into damaged areas of knee articular cartilage.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-02T08:30:46.871993+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001168","title":"Spatial transcriptomics data (Visium) of 8 healthy human rectum and colon samples","description":"Raw fastq files from human rectum and colon healthy samples. This data comprises 8 samples (each with one R1 fastq and one R2 fastq files). these are 5 healthy colon samples and 3 healthy rectum samples. They were subjected to either a FFPE or RRST protocol. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001169","title":"Analysis of Somatic Mutations from Liquid Biopsy-Derived cfDNA in Advanced Cancers","description":"This study aims to identify somatic mutations and characterize potential neoantigens for immunotherapeutic targeting using paired whole-exome sequencing (WES) of germline DNA and plasma-derived circulating cell-free DNA (cfDNA) from patients with advanced-stage cancers. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-26T17:02:52.982903+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001170","title":"Exome sequencing","description":"Exome sequencing of patient tumor biopsy, cfDNA and normal PBMC DNA samples","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-26T17:04:50.735414+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001171","title":"RNA-Seq","description":"RNA sequencing of patient tumor biopsy samples. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-26T17:04:50.735414+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001172","title":"ChIP-seq data in MSC_Pat and EWIma1 (FLI1 & H3K27ac)","description":"Ewing sarcoma is characterized by pathognomonic translocations fusing most frequently EWSR1 with FLI1 (EF1). In addition, Ewing sarcoma can also display alterations in STAG2, TP53 and CDKN2A (SPC). Starting from Ewing sarcoma derived human mesenchymal stem cells (MSCpat), we recapitulated this translocation and SPC alterations using a CRISPR/cas9 approach and generated a bona fide Ewing sarcoma model (EWIma1) displaying transcriptomic and epigenetic hallmarks of EwS.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[34341072],"external_links":null,"is_released":true,"released_date":"2025-10-02T19:00:27.596726+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001173","title":"RNA-seq data in hMPC, MSC_Pat and EWIma","description":"Ewing sarcoma is characterized by pathognomonic translocations fusing most frequently EWSR1 with FLI1 (EF1). In addition, Ewing sarcoma can also display alterations in STAG2, TP53 and CDKN2A (SPC). Starting from Ewing sarcoma derived human mesenchymal stem cells (MSCpat), we recapitulated this translocation and SPC alterations using a CRISPR/cas9 approach and generated a bona fide Ewing sarcoma model (EWIma1) displaying transcriptomic and epigenetic hallmarks of EwS.","abstract":null,"study_type":"RNASeq","pubmed_ids":[34341072],"external_links":null,"is_released":true,"released_date":"2025-10-02T19:00:27.596726+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001174","title":"CIAO Clinical Trial","description":"Whole exome and RNA sequencing for samples from CIAO (Checkpoint Inhibitors Assessment in Oropharynx cancer) (NCT03144778) clinical trial testing neoadjuvant anti-PD-L1 durvalumab with or without the anti-CTLA-4 tremelimumab in oropharynx cancer","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-29T09:32:59.079234+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001175","title":"HNSCC Patients Treated with Immune Checkpoint Blockade","description":"HNSCC Patients Treated with Immune Checkpoint Blockade","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-29T09:33:02.646055+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001176","title":"Transcriptome analysis in human testis during ageing","description":"The molecular mechanism allowing the human testis to age without major loss of function remains elusive. In this study, we aimed to investigate the transcriptomic changes taking place in human testis during the ageing process. In order to isolate the effects of ageing, we selected samples with full spermatogenesis and no significant differences in cellular composition. We performed whole transcriptome sequencing and evaluated differential gene expression as well as alternative transcript usage between young (24-31 years old), middle-aged (41-45 years old), and aged (54-75 years old) samples.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-15T17:15:53.601422+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001177","title":"Vaccine-Expanded Plasmablast-like B Cells Are Associated with Response to Dendritic Cell Therapy in Metastatic Melanoma","description":"Dendritic cells (DCs), either monocyte-derived (moDCs) or naturally circulating, have been employed in cancer treatment across both metastatic and adjuvant settings. DC vaccines (DC Vax) are capable of inducing tumor-specific immune responses, yet clinical outcomes have thus far fallen short of expectations. Here, we performed a multi-omics analysis of the apheresis product, including CD14⁺ monocytes, and the final DCVax formulation. Among all the components analyzed, the most striking finding was the unexpected presence of CD19⁺ B cells within the DC Vax formulation, which distinguished Responders from Non-Responders to moDC vaccination in metastatic melanoma. The abundance of B cells in DC Vax correlated with their peripheral frequency; however, within the vaccine, these cells acquired a CD20lowCD27hiCD38hi plasmablast-like phenotype, distinct from their autologous circulating B-cell precursors. Notably, a parallel observation was made in Responders, whose pre-treatment lesions were enriched in B cells organized as Tertiary Lymphoid Structures. These results underscore the importance of B cells in both baseline immunity and DCVax formulation, hinting at unexplored mechanisms by which they may influence vaccine effectiveness.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-11T17:31:09.208687+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001178","title":"Exome Sequencing of familial and sporadic Meniere disease patients","description":"This study aims to characterize the genetic architecture of spanish patients diagnosed with Meniere disease (MD), focusing on both familial (FMD) and sporadic (SMD) forms, by analyzing coding variants. Whole-exome sequencing was performed on these patients, and variants were called and annotated using the nf-core/sarek bioinformatics pipeline, including alignment to the GRCh38 reference genome. The resulting data provide a curated resource for investigating the potential genetic contribution to the pathophysiology of MD. All data will be made available for reuse under controlled access.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-11T17:31:06.185824+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001179","title":"Germline variants in UHRF1 are associated with multi-locus imprinting disturbance in humans and  mice ","description":"Genomic imprinting provides is an epigenetic process crucial for normal development and is disrupted in congenital imprinting disorders(CIDs). There is great interest in the clinical consequences and aetiology of multilocus imprinting disturbance(MLID) which occurs in some individuals with CID, though the cause of MLID is unknown in most cases. We investigated a kindred with a CID and MLID and identified a rare genetic variant in the UHRF1 gene which has a critical role in the establishment and maintenance of DNA methylation. We generated a mouse model and found that the equivalent Uhrf1 variant was associated with prenatal lethality and disruption of normal imprinting mechanisms. These findings support UHRF1 as a novel candidate gene for CIDs with MLID.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-28T12:40:25.583927+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001180","title":"Single-cell sequencing of pancreatic ductal adenocarcinoma patient samples ","description":"In this study, we evaluated the combined effects of immunotherapy with dual immune checkpoint inhibitors durvalumab and tremelimumab, local tumor ablation with microwave energy, and gemcitabine on progression-free survival in twelve patients with non-metastatic unresectable locally advanced pancreatic adenocarcinoma. The tumor microenvironment and peripheral blood immune cell repertoire of patient samples were characterized using single-cell transcriptomic sequencing. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001181","title":"Gut metagenome associations with extensive digital health data in a volunteer-based EstMB cohort second timepoint data","description":"As part of the Estonian Biobank, we established the Estonian Microbiome Cohort which includes stool, oral and plasma samples from 2,509 participants and is supplemented with multi-omic measurements, questionnaires, and regular linkages to national electronic health records. Out of the 2,509 Estonian Microbiome Project participants, a sub-cohort of over 300 individuals provided an additional stool sample after a median follow-up period of 4.4 years. All participants of the EstMB cohort gave informed consent for the data and samples to be used for scientific purposes. In the second time point, the participants were instructed to send the samples by post immediately after taking the sample and time their sample collection to avoid shipping on the weekends. In the study, by utilising retrospective medication usage data from the electronic health records and the Estonian microbiome cohort shotgun metagenomics data set (n = 2,509), we systematically evaluate the long-term effects of antibiotics and human-targeted medications on the gut microbiome. We show that past usage of medications is associated with the gut microbiome. For example, the effects of antibiotics, psycholeptics, antidepressants, proton pump inhibitors, and beta-blockers are detectable several years after use. Furthermore, by analysing a subcohort (n >300 individuals) from the second time point, we show that similar changes in the gut microbiome occur after treatment initiation or discontinuation, possibly indicating causal effects.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-01T14:59:57.54064+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001182","title":"WGS of IPMN-PDAC Data","description":"This study investigates IPMN-PDAC development using whole-genome sequencing (WGS) data from 42 tumours collected from multiple regions and 12 matched normal samples. Sequencing was performed on Illumina platforms with 150 bp paired-end reads.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-14T11:58:56.550189+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001183","title":"Effects of Rhinovirus A infection on healthy and severe asthmatic epithelia, in vitro","description":"In asthma, chronic inflammation and airway remodeling profoundly alter the epithelial landscape, characterized by a decrease in multiciliated cells and a hyperplasia of mucus-secreting goblet cells. Current therapeutics primarily target the interplay between immune and epithelial cells to mitigate these effects. However, the epithelial-intrinsic mechanisms driving airway remodeling remain underexplored. \r\nTo identify molecular regulators of airway remodeling, we reconstructed airway epithelia using basal cells from healthy or severe asthma donors. Using single-cell RNA sequencing, we analyzed differential cellular and molecular features at baseline, following rhinovirus (RVA16) and upon recovery. Single-cell RNAseq was performed with Parse Biosciences Evercode WT.\r\nThe dataset is composed of 43 samples with 61,682 cells from 3 healthy donors and 4 severe asthma patients. Samples were collected at 4 different timepoints post rhinovirus A (RVA) infection (3 samples on day 0, 14 samples on day 3, 13 samples on day 7 and 13 samples on day 14). At each timepoint, non-infected samples were included (CTRL).","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001184","title":"Paraganglioma Smart-Seq2 Single Nuclei Sequencing Data","description":"Paraganglioma is a rare neuroendocrine tumor that originates from chromaffin cells of the adrenal medulla or extra-adrenal paraganglia. This study aims to investigate the heterogeneity of this tumor and to identify potential biomarkers associated with its malignancy. To achieve this, we performed single-nucleus RNA sequencing of human paraganglioma samples using the SMART-Seq2 protocol.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-27T10:09:01.343596+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001185","title":"Single cell RNA sequencing of human embryonic forebrain after slice culturing for between four weeks and one month","description":"With the aim of verifying normal tissue development in our Organotypic Timelapse recording with Transcriptomic Readout (OTTR) live tissue imaging method, we performed single cell RNA sequencing in organotypic slice cultures containing labelled cells from virally delivered ubiquitous Enhanced yellow fluorescent protein (EYFP)-expression. Human fetal cortices of  PCW 7.5-10.5 were cut into strips along the dorso-ventral axis and directly placed en face, ventricular side down, on PTFE culturing membranes. To assess tissue health with our culturing method, we performed single cell RNA-seq analysis of the cortical explants (using adjacent slices from the same samples subjected to timelapse imaging). We cultured these control slices for four days in vitro (mimicking the start of a live imaging experiment after lentiviral infection and expression of EYFP), 11 days in vitro (corresponding to the end of one week of live imaging), and for two weeks and one month in vitro.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-01T14:38:00.642821+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001186","title":"Re-evaluation of human mitochondrial DNA methylation reveals signals consistent with technical artifacts","description":"The existence and functional relevance of mitochondrial DNA (mtDNA) methylation remain controversial. We assessed 5mC and 5hmC in human brain, blood, and related cancers using both enzymatic and native DNA sequencing. While nuclear DNA exhibited expected methylation patterns, mtDNA consistently showed negligible methylation levels, indistinguishable from technical noise. Elevated methylation in nuclear-embedded mitochondrial sequences demonstrates a clear potential to confound mtDNA methylation measurements. Furthermore, technical discrepancies in mtDNA methylation were observed, underscoring the need for careful evaluation when interpreting data generated using earlier sequencing workflows. Our findings provide evidence against the presence of 5mC or 5hmC in mtDNA under the physiological and pathological conditions studied.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-20T15:13:18.800228+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001187","title":"WGS data for ctDNA monitoring for NSCLC in TRACERx","description":"Ultrasensitive circulating tumour DNA (ctDNA) detection can stratify clinical risk in early-stage non-small cell lung cancer (NSCLC). Here, we applied a whole-genome, tumour-informed approach to study ctDNA in more than 400 NSCLC of the TRACERx project","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-01T17:22:40.949331+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001188","title":"Novel genome editing strategies to uncover genotype-phenotype correlations in Polycystic Kidney Disease: a proof-of-concept","description":"Bulk RNA-seq of genome-edited HEK293T cell lines engineered to model specific PKD1 variants. This dataset enables the exploration of genotype-phenotype correlations in Polycystic Kidney Disease (PKD)","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-01T09:27:02.099243+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001189","title":"Single nucleus RNA sequencing of isolated NK cells and CD56+ T cells from digested NSCLC tumor lesions","description":"In order to explore the intratumoral NK cell heterogeneity at a transcriptomic level, we performed matched single nucleus RNA sequencing of isolated CD45+CD3+CD56+ immune cells from 11 NSCLC patients.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-10T11:04:13.355736+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001190","title":"Single nucleus ATAC sequencing of isolated NK cells and CD56+ T cells from digested NSCLC tumor lesions","description":"In order to explore the intratumoral NK cell heterogeneity at an epigenetic level, we performed matched single nucleus ATAC sequencing of isolated CD45+CD3+CD56+ immune cells from 11 NSCLC patients.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-10T11:04:13.355736+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001191","title":"Hematopoietic Tet2 inactivation enhances the response to checkpoint blockade immunotherapy","description":"Somatic mutations inactivating TET2 are among the most common drivers of clonal hematopoiesis (CH). While TET2 inactivation is associated with monocyte-derived inflammation and improved chimeric antigen-receptor-T cell function, its impact on immunotherapy response is unknown. In murine models, hematopoietic Tet2 mutation enhanced the immune checkpoint blockade (ICB) response via the combined presence of phagocytes, CD4 and CD8 T cells. This effect was lost with myeloid- or T-cell restricted Tet2 inactivation, or in mice with 20% Tet2-mutant hematopoiesis. Mechanistically, in Tet2-mutant tumor-infiltrating leukocytes (TILs), ICB preferentially restricted cell states linked to tumor progression while inducing anti-tumor states. Tet2-mutant monocytes activated costimulatory programs, while Tet2-mutant T cells showed enhanced T cell memory signatures, alongside decreased exhaustion and regulatory phenotypes. This murine data was clinically relevant, since tumors from colorectal cancer and melanoma patients with TET2 driver mutation-CH (TET2-CH) showed enhanced immune infiltration, inflammation, and T cell activation. In melanoma patients treated with ICB, TET2-CH was associated with 6-fold greater odds of clinical benefit. Collectively, we demonstrate that hematopoietic Tet2 inactivation primes leukocytes for anti-tumor states associated with immunotherapy response and provides a potential biomarker for personalized therapy.\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-27T10:50:34.622457+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001192","title":"Fluctuating DNA methylation tracks cancer evolution at clinical scale","description":"Long-read Nanopore data of fCpGs from Gabbutt & Duran-Ferrer (2025) for developing the EVOFLUx method to study cancer evolution via DNA methylation fluctuations.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-19T13:41:40.391632+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001193","title":"Mixed Whole Genome Duplication States in High Grade Serous Ovarian Cancer ","description":"Mixed Whole Genome Duplication States in High Grade Serous Ovarian Cancer \r\nLimited evidence exists on the extent and impact of spatial and temporal heterogeneity of high grade serous ovarian cancer (HGSOC) on tumour evolution and patients surgical and clinical outcome. We investigated this through systematic mapping of multi-site tumours at initial presentation and matched relapse from 22 chemo-naïve HGSOC patients with high tumour load.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001194","title":"Generation of hypoimmunogenic induced pluripotent stem cells by CRISPR-Cas9 system and detailed evaluation for clinical application","description":"We established hypoimmunogenic human induced pluripotent stem cells (iPSCs) to minimize the immune rejection caused by mismatches of HLA type. Here, we optimized the protocol for good manufacturing practice (GMP)-compatible CRISPR-Cas9 genome editing to deplete the three gene locus (HLA-A, HLA-B, and CIITA genes) simultaneously in HLA homozygous iPSCs. RNA-seq and flow cytometry analyses confirmed the successful depletion of HLAs, and lineage-specific differentiation into cardiomyocytes was verified.","abstract":null,"study_type":"RNASeq","pubmed_ids":[35755947],"external_links":null,"is_released":true,"released_date":"2025-09-02T08:31:32.328993+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001195","title":"Perioperative nivolumab or nivolumab plus ipilimumab in resectable diffuse pleural mesothelioma: Primary phase 2 trial results with ctDNA residual disease analyses","description":"This data set includes sequence files from whole genome sequencing of tumor (n=28), normal (n=28), and blood (n=113) specimens from a phase 2 clinical trial of neoadjuvant nivolumab and nivolumab/ipilimumab in resectable diffuse pleural mesothelioma (NCT03918252).","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-01T09:06:00.653675+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001196","title":"Impact of cryopreservation on transcriptome analysis of peripheral blood mononuclear cells","description":"To investigate the effect of cryopreservation on PBMCs, we conducted an experiment using samples from three healthy donors under four conditions: fresh PBMCs, PBMCs subjected to a single freeze–thaw cycle, PBMCs refrozen in freezing mix, and PBMCs refrozen in TRIzol. This resulted in a total of 12 samples (three replicates per condition). RNA was extracted from all PBMC samples using the Qiagen miRNeasy Mini Kit, followed by polyA RNA sequencing on the Illumina NovaSeq 6000 platform. Blood was collected from one male and two female adult donors. Sequencing yielded high-quality data, with an average of 27.8 million reads per sample and over 94% of bases exceeding a Q30 quality score.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-20T15:15:59.45462+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001197","title":"Transcriptomic analysis of the response of AC16 cardiomyocytes with the rs1136201 variant to trastuzumab","description":"This study investigates the implication of the rs1136201 variant in cardiotoxicity in in vitro models of human cardiomyocytes exposed to trastuzumab.\r\n\r\nMethods: We generated AC16 ventricular cardiomyocyte cell models representing the three genotypes of the rs1136201 variant and performed transcriptomic analysis following trastuzumab exposure on cells expressing increasing levels of expression of HER2 (i.e. low, medium, high)","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-19T16:56:15.896782+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001198","title":"Somatic L1 retrotransposition dynamics in high-grade serous ovarian cancer","description":"Somatic L1 retrotransposition was mapped in high-grade serous carcinoma (HGSC) tumors using LDI-PCR/Nanopore-seq method. This method identifies somatic L1 insertions originating from two active L1 loci at chr22q12.1 and chrXp22.2. Multiple tumors from same patient were utilised to understand L1-mediated intrapatient heterogeneity.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-26T11:49:39.703603+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001199","title":"scRNA-seq data of FOXN1heterozygous patients and cord blood","description":"Single cell sequencing was performed from sorted CD45+ lymphocytes from two FOXN1het patients and one cord blood sample from frozen cryopreserved samples to undestand the shifts in immune cell populations in pateints with FOXN1 heterozygous deficiency. Each sorted population was labelled individually via multiplexing antibodies with subsequent Abseq staining before pooling and conducting the BD Rhapsody pipeline to generate scRNA-seq data. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-23T16:07:45.852768+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001200","title":"Exploring Extracellular Vesicle microRNAs in Usher Syndrome Type 1B: Tear-Derived EVs as Indicators of Retinal Health","description":"The goal of this study was to explore extracellular vesicles (EVs) from human tears and iPSC-derived RPE cells as biomarkers for Usher syndrome type 1B (USH1B), a rare inherited disorder causing deafness and retinitis pigmentosa. Researchers found that tear EVs showed higher levels and diversity of miRNAs, making them a promising non-invasive source for diagnosing USH1B. In contrast to patient-derived RPE cells, which did not express MYO7A protein despite similar expression levels in controls, the study identified specific microRNA signatures associated with retinal degeneration in both tear EVs and RPE-derived EVs. The findings suggest that tear EVs can serve as a useful biomarker for USH1B diagnosis, monitoring, and therapeutic development. Overall, this research aims to contribute to our understanding of disease mechanisms and identify potential targets for treatment in patients with Usher syndrome type 1B.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-29T12:28:08.262229+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001201","title":"RNA004 Nanopore DRS of peripheral blood","description":"Direct RNA Sequencing offers the capability of standard transcriptomic analyses + RNA modification analysis, which holds promising applications for future clinical workflows. To this end, we tested the newly available RNA004 kit on human peripheral blood and provide orthogonal GLORI measurement for benchmarking of m6A-detection.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-22T13:16:54.680205+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001202","title":"RESOLVE_trial_targeted_sequencing_data","description":"RESOLVE: Abemaciclib + Letrozole +/_- Metformin, Zotatifin, or Gedatolisib in Endometrial or Low-Grade Serous Ovarian Cancer","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-21T16:39:24.620512+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001203","title":"A Single-Cell and Spatial Atlas of Early Human Olfactory Development","description":"The human nasal region is a complex anatomical structure comprising neural crest- and placode-derived lineages, yet its developmental dynamics in humans remain poorly understood due to limited access to fetal tissue and challenges in resolving its spatial and cellular complexity. We built a single-cell and spatial transcriptomic atlas of the human fetal nasal region from 10 fetuses spanning post-conceptional weeks 7 to 12. Using snRNA-seq, we identify 34 cell types in the fetal nasal region and reconstruct lineage trajectories in the olfactory epithelium (OE). \r\nSpatial analyses uncover regionalized OE organization, dorsoventral gradients of olfactory receptors (ORs) and high-resolution OR expression. Combining snRNAseq and MERFISH, we reveal early onset of OR gene expression, with most olfactory sensory neurons (OSNs) following the one neuron-one receptor rule already during the first trimester.  This work provides the first integrated molecular and spatial framework of early human nasal region and it provides an unprecedented molecular blueprint of the human olfactory system development. In addition, this  study offers a foundational resource for embryologists and developmental biologists investigating sensory neurogenesis, epithelial patterning, and congenital diseases.\r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-10T17:54:47.203865+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001204","title":"Transcriptional characterization of human innate lymphoid cells (ILCs) and natural killer (NK) cells from fresh umbilical cord blood","description":"The heterogenicity of cord blood ILCs (ILC1, ILC2, ILC3) and NK cells in humans has so far not been assessed. In this study, we sorted from fresh cord blood the respective cell types from 3 donors and performed single-cell transcriptome analysis. To achieve high resoluation, each sorted population was labelled individually via multiplexing antibodies and subsequent Abseq staining before pooling. To determine single-cell transcriptomes the BD Rhapsody pipeline was performed. This is the first data set to characterize human ILCs and NK cells at such depth.\r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-23T16:07:47.928239+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001205","title":"Rituximab-treated lymphoma patients show correlated deficiency in serological and T cell Spike-specific response after SARS-CoV-2 vaccination: insights from the CORSA Study.","description":"This study is part of the CORSA trial (NCT04345315), a prospective multicentric research project conducted by the Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” to investigate the immunologic response to mRNA SARS-CoV-2 vaccines in patients with hematologic malignancies (HM) and healthy individuals as controls (HC). The data in this repository refer to two subcohorts: 7 healthy controls and 10 lymphoma patients, randomly selected. Whole blood samples were collected to characterize T cell receptor (TCR) repertoire specificity against SARS-CoV-2 proteins before and after two BNT162b2 vaccination cycles, at baseline (before vaccination), 50 days after the first dose (V1), and 6 months after the first dose (V3). All participants were vaccinated under the Italian national campaign and provided informed consent following the Declaration of Helsinki. We investigated SARS-CoV-2-specific T cell responses through TCR repertoire profiling and examined correlations between serological and cellular responses in both patient and control groups. Using Next-Generation Sequencing (NGS) to characterize the CDR3 sequences of TCR β-chains from peripheral blood, we assessed clonal expansion (depth) and diversification (breadth) of SARS-CoV-2-specific T cell clonotypes over time, aiming to understand how cancer and its treatment influence vaccine-induced immunity in immunocompromised individuals.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-25T11:25:12.662324+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001206","title":"The acute effects of morning bright light on the human white adipose tissue transcriptome: exploratory post hoc analysis ","description":"The circadian rhythm of the central brain clock in the suprachiasmatic nucleus (SCN) is synchronized by light. White adipose tissue (WAT) is one of the metabolic endocrine organs containing a molecular clock, and it is synchronized by the SCN; excess WAT is a risk factor for health issues including type 2 diabetes mellitus (DM2). We hypothesized that bright-light exposure would affect the human WAT transcriptome. Therefore, we analyzed WAT biopsies from two previously performed randomized cross-over trials (trial 1: lean healthy men, and trial 2: men with obesity and DM2). RNA sequencing results showed major group differences between men with obesity and DM2 and lean healthy men, as well as a differential effect of bright light exposure. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-22T13:15:19.901091+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001207","title":"Single-Cell DNA Methylation Phylogeny Uncovers Alternative Epigenetic Pathways for MDS Transformation to AML","description":"This project investigates the transformation of myelodysplastic syndrome (MDS) to secondary acute myeloid leukemia (sAML), particularly after hypomethylating agent (HMA) therapy, a process linked to therapy resistance and poor survival using single-cell DNA methylation data together with sc-DNA, sc-Prot and sc-RNA data.The findings reveal novel epigenetic drivers of therapy resistance and sAML.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-05T10:43:54.864767+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001208","title":"RNA-seq and scRNA/TCR-seq data for publication: \"Pharmacological inhibition of nonsense-mediated mRNA decay enhances anti-tumour immunity\"","description":"RNA-seq and scRNA/TCR-seq data from patient-derived fragments (PDFs) analysed in publication by R. Vendramin, H. Fu, S. Fernandez Patel, Y. Zhao et al.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-16T16:48:35.090418+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001209","title":"cfDNA in health","description":"This study investigates baseline methylome and fragmentomic profiles in circulating cell-free DNA (cfDNA) from healthy individuals. Two cohorts were assembled: a diurnal cohort to evaluate temporal variation in cfDNA features, and a cross-sectional cohort to assess inter-individual variability. The project’s goal was to generate a reference dataset for plasma cfDNA to support future studies in biomarker discovery and disease detection.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-08-20T15:05:37.905912+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001210","title":"Bulk and RIP-seq transcriptome datasets from skin fibroblasts in PTBP1- and PTBP2-related disorders","description":"PTBP1- and PTBP2-related disorders are rare human conditions that cause variable neurodevelopmental phenotypes, including intellectual disability and behavioral problems such as autism spectrum disorder, anxiety, aggressiveness, and attention disorders, with or without hyperactivity. PTBP1-related disorder is also associated with skeletal dysplasia. In this study, we generated bulk RNA sequencing and RNA immunoprecipitation sequencing (RIP-seq) data from skin fibroblasts obtained from patients and healthy controls.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-01T17:20:49.020306+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001211","title":"Elevated circulating tumor cells reflect high proliferation and genomic complexity in multiple myeloma - WGS validation cohort","description":"This reposiroty contains bulk WGS data generated by Blood Cancer Research Group (Ostrava, Czech Republic) as a part of publication named \"Elevated circulating tumor cells reflect high proliferation and genomic complexity in multiple myeloma\" published in Hemapshere. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-13T11:44:44.299406+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001212","title":"Elevated circulating tumor cells reflect high proliferation and genomic complexity in multiple myeloma - RNA validation cohort","description":"This reposiroty contains bulk RNA data generated by Blood Cancer Research Group (Ostrava, Czech Republic) as a part of publication named \"Elevated circulating tumor cells reflect high proliferation and genomic complexity in multiple myeloma\" published in Hemapshere. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-13T11:44:47.23275+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001213","title":"Expanding the SPTBN1 Spectrum: A Case of Neurodevelopmental Disorder with GI and Musculoskeletal Involvement","description":"Background:\r\nMutations in the SPTBN1 gene, which encodes the βII-spectrin protein, are associated with a recently described neurodevelopmental syndrome characterized by developmental delay, intellectual disability, autistic traits, seizures, and dysmorphic features. While the phenotypic spectrum continues to evolve, gastrointestinal (GI) involvement and vertical transmission remain rarely reported features.\r\nCase Presentation:\r\nWe describe a 13-year-old male from Georgia with a heterozygous missense mutation in SPTBN1 (c.3799C>G, p.Leu1267Val), inherited from his clinically unaffected mother. The patient presented with cognitive and motor delays, autistic traits, behavioral challenges, feeding difficulties, growth delay, musculoskeletal anomalies (pectus excavatum, pes planus), and persistent GI symptoms including abdominal pain and gallbladder sludge. Despite therapy with ursodeoxycholic acid and nutritional counseling, the gallbladder abnormalities persisted over a 12-month follow-up. Feeding therapy could not be initiated due to access barriers, although parental efforts led to modest dietary improvement. Upon recent visit pes planus was also confirmed.\r\nConclusion: This case contributes to the growing body of literature on SPTBN1-related neurodevelopmental disorders, highlighting the potential for a broader phenotypic spectrum than currently recognized. In addition to the well-documented behavioral, cognitive, and musculoskeletal features, our patient presented with notable gastrointestinal involvement—specifically, gallbladder sludge and feeding disorder—which are not commonly reported in association with SPTBN1 mutations. Although causality cannot be established from a single case, the observed GI manifestations may be indirectly related to underlying neurobehavioral features such as ASD and associated eating disorders. The identification of a vertically transmitted missense variant (c.3799C>G, p.Leu1267Val) adds to the limited but growing evidence of inherited SPTBN1 mutations, expanding our understanding of transmission patterns. Given the novelty of the findings, we emphasize the need for multidisciplinary management, including feeding and behavioral therapy, as well as longitudinal follow-up to assess developmental, nutritional, and hepatobiliary outcomes. Future studies and case series are warranted to determine whether pes planus, pectus excavatum, gastrointestinal symptoms, including biliary tract involvement, represent an underrecognized component of the SPTBN1 phenotypic spectrum.\r\n","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-01T12:20:02.667883+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001214","title":"Analysis of transcriptomic landscape of iPSC-derived neurons in Williams Syndrome","description":"To analyse the transcriptomic changes in iPSC-derived neuronal cells derived from individuals with Williams syndrome vs. controls at different stages of neuronal maturation. This was done to better understand how the deletion responsible for WS alters neuronal development thereby resulting in the characteristic WS phenotype","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-17T10:12:42.87079+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001215","title":"A distinct monocyte cellular state links systemic immune dysregulation to pulmonary impairment in long COVID","description":"Long COVID is a debilitating disease with a very heterogeneous disease aetiology. In this study, we collected blood from Long COVID patients and generated single-cell multiomics datasets. The samples collected were both longitudinal and cross-sectional cohorts. The aim of the study involved examining the transcriptomic and epigenetic landscape of circulating immune cells from these samples to better understand the disease imprints.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-10T17:45:16.496462+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001216","title":"A distinct monocyte cellular state links systemic immune dysregulation to pulmonary impairment in long COVID","description":"This is an independent cohort of Long COVID patients recruited from a rehabilitation centre. These patients had Long COVID from 8 months to more than 2 years since their acute COVID-19 disease. PBMC from these patients were collected and single cell transcriptomics dataset was generated.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-10T17:45:19.072023+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001217","title":"Response to tumor-infiltrating lymphocyte adoptive therapy is associated with preexisting CD8+ T-myeloid cell networks in melanoma","description":"Adoptive cell therapy (ACT) using ex vivo–expanded tumor-infiltrating lymphocytes (TILs) can eliminate or shrink metastatic melanoma, but its long-term efficacy remains limited to a fraction of patients. Using longitudinal samples from 13 patients with metastatic melanoma treated with TIL-ACT in a phase 1 clinical study, we interrogated cellular states within the tumor microenvironment (TME) and their interactions. We performed bulk and single-cell RNA sequencing, whole-exome sequencing, and spatial proteomic analyses in pre- and post-ACT tumor tissues, finding that ACT responders exhibited higher basal tumor cell–intrinsic immunogenicity and mutational burden. Compared with nonresponders, CD8+ TILs exhibited increased cytotoxicity, exhaustion, and costimulation, whereas myeloid cells had increased type I interferon signaling in responders. Cell-cell interaction prediction analyses corroborated by spatial neighborhood analyses revealed that responders had rich baseline intratumoral and stromal tumor–reactive T cell networks with activated myeloid populations. Successful TIL-ACT therapy further reprogrammed the myeloid compartment and increased TIL-myeloid networks. Our systematic target discovery study identifies potential T-myeloid cell network–based biomarkers that could improve patient selection and guide the design of ACT clinical trials.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[38306416],"external_links":null,"is_released":true,"released_date":"2025-09-09T11:20:36.759319+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001218","title":"CNA differences between RNA-based subtypes of PDAC","description":"Pancreatic ductal adenocarcinomas (PDAC) have a dismal prognosis with a 5-year survival of <5%. Chemoresistance and recurrences, seen in approximately 70% of PDAC patients, may partly be explained by intratumor heterogeneity (ITH) through which tumors may develop ‘escape routes’. In the Pancreas Multibiopsy (PM)-project we have obtained multiple fragments from pancreatic and other peri-ampullary carcinomas in order to reveal potential ITH and identify genetic aberrations that predict outcome after surgery and response to chemotherapy. CNA-profiles were used to complement the characterization of liabilities in PDAC that we identified previously using RNAseq in the form of epithelial, secretory, compound pancreatic, and mesenchymal subgroups that showed survival outcomes. Comparison of CNA-profiles between these transcriptomics-based subgroups (with 8, 3, 6, and 6 tumors respectively per group) showed differences, ranging from ‘quiet’(i.e. hardly any CNA) to ‘wild’(i.e. lots of CNA), but these were not statistically significant (Chi2 0.09). When differentiating between the classical and basal-like molecular subtypes of PDAC differences in CNA (high or low) were even less statistically significant (Chi2 0.292).","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[31941932],"external_links":null,"is_released":true,"released_date":"2025-09-01T09:40:31.196877+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001219","title":"Head and neck tumor organoid biobank for modelling individual responses to radiation therapy according to the TP53/ HPV status","description":"Head and neck cancers (HNC) represent an extremely heterogeneous group of diseases with a poorly predictable therapy outcome. Here, we have established a comprehensive molecularly and functionally characterized head and neck organoid biobank recapitulating the clinically relevant subtypes of TP53 mutant and human papillomavirus type 16 (HPV 16) infection-driven HNC. \r\nOrganoids were exposed to radiotherapy and genetically engineered normal and tumor organoids were used for testing the direct functional consequences of TP53-loss and HPV infection. We identified subtype-associated transcriptomic signatures and pathological features, including sensitivity to TP53 stabilization by the MDM2 inhibitor Nutlin-3. TP53 loss-of-function alone was insufficient to promote radiation resistance, whereas HPV 16 oncogenes E6/E7 mediated radiosensitivity via induction of cell cycle arrest.","abstract":null,"study_type":"RNASeq","pubmed_ids":[40045309],"external_links":null,"is_released":true,"released_date":"2025-09-01T12:15:37.527462+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001220","title":"Spatial Biology of Cancer of Unknown Primary Reveals Origin, Vulnerabilities, Divergent Oncogene-Driven Stemness and Inflammatory-Immune Related Pathways","description":"Cancer of unknown primary (CUP) represents not only a biological conundrum, but also a major cause of neoplasm-associated death in Western countries. The singularity of these metastases, where the source tumor remains hidden, prevent cancer-type efficient cancer treatments. Additionally, our limited understanding of the molecular and cellular pathways involved in their genesis are linked to the poor clinical outcome of patients with CUPs. To address this, we have integrated distinct spatial transcriptomic technologies with genetic and clinicopathological parameters in CUP cases to unveil their biological roots, improve diagnosis, and provide specific therapies. Our findings reveal that the resolution of transcriptional signatures in the space of paraffin-embedded slides constitutes an excellent tool to provide the tumor-of-origin (TOO) of these samples, with non-small cell lung cancer being the main culprit. In addition, the spatial expression of thousands of genes confers a unique opportunity to pinpoint targets for tailored treatments such as those associated with HER2 and MET overexpression. Most important, our study indicates the existence of two trajectories yielding CUPs: one enriched in oncogene-derived hyperproliferation markers and stemness features (ONC-CUP) that drives an extremely short survival; and another (IMI-CUP) that is characterized by chronic inflammation and immune related phenotypes linked to relatively better outcome and potentially responsive to immunotherapy.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001221","title":"Patient-derived organoids as predictive models for drug testing and repurposing in glioblastoma therapy","description":"Glioblastoma multiforme (GBM) remains a highly aggressive brain tumor with limited treatment options and poor prognosis. Temozolomide (TMZ) is the only approved first-line therapy, but frequent resistance limits its efficacy, highlighting the urgent need for alternative treatments. Patient-derived glioblastoma organoids (GBOs) offer a promising preclinical model for personalized drug testing and therapy development.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-27T11:26:21.332965+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001222","title":"Determining off-target effects of splice-switching antisense oligonucleotides using short read RNAseq in neuronally differentiated human induced pluripotent stem cells","description":"Splice-switching antisense oligonucleotides (AONs) are designed to modulate pre-mRNA splicing, thereby for instance restoring protein expression or modifying the eventual protein to restore its function or reduce its toxicity. To determine off-target effects, RNA from neuronally differentiated human induced pluripotent stem cells transfected with splice-switching AONs was sequenced. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-19T10:31:22.384085+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001223","title":"APOL1 Risk Variants Induce Metabolic Reprogramming of Podocytes in Patient-Derived Kidney Organoids","description":"Apolipoprotein L1 (APOL1) high-risk genotypes G1 and G2 are responsible for the increased risk of chronic kidney disease (CKD) in the African-American population, especially in the presence of interferon gamma (IFN-γ). Here, we applied single cell transcriptomics on kidney organoids generated from patient-derived induced pluripotent stem cells (iPSCs) to model human APOL1 nephropathy. iPSCs were generated from fibroblasts of two patients with APOL1 nephropathy homozygous for G1 or G2 risk variants, and an isogenic control (G0) was created by gene correction. Kidney organoids were generated according to previously published protocol (Takasato M et al. Nat. Protoc. 2016) and treated with IFN-γ for two days to induce APOL1. Twenty-four hours after IFN-γ removal, treated organoids from all three lines that were cultured in parallel were harvested for single cell transcriptomics.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-31T14:07:12.553425+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001224","title":"Ultra-sensitive tumor-informed ctDNA monitoring of treatment response in advanced esophagogastric cancer patients","description":"To explore whether ultra-sensitive circulating tumor DNA (ctDNA) profiling enables earlier prediction of treatment response and detection of disease progression, we applied NeXT Personal, an ultra-sensitive bespoke tumor-informed liquid biopsy platform, to profile tumor samples from the KeyLargo study, a phase II trial in which metastatic esophagogastric cancer (mEGC) patients received capecitabine, oxaliplatin, and pembrolizumab. A total of 24 patients were evaluated, and all were ctDNA-positive at baseline. ctDNA levels varied from 406,067 down to 1.5 parts per million (PPM) with a median limit of detection of 2.03 PPM. ctDNA dynamics were highly correlated with changes in tumor size (ρ = 0.59, p = 7.3×10-9). Lack of early molecular response (50% or greater decrease in ctDNA levels at first available time point after 30 days, C2D1 or C4D1) was associated with worse overall survival (OS) (HR 6.6, 95% CI 1.8-24.1, p = 0.005) and progression-free survival (PFS) (HR 15.4, 95% CI 2.7-87.0, p = 0.002). Lack of molecular clearance of ctDNA was associated with worse OS (HR 6.9, 95% CI 1.5-30.8, p = 0.012) and PFS (HR 19.2, 95% CI 2.4-152.8, p = 0.005). Molecular progression (ctDNA increase) preceded imaging-derived progression by a median lead time of 65 days. These results suggest that ultra-sensitive liquid biopsy approaches could improve treatment decision-making for mEGC patients receiving chemotherapy and immunotherapy.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-01T16:50:20.001388+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001225","title":"Identifying mutations in patient-derived melanoma DCC lines","description":"To identify mutations that cause resistance, we analyzed two patient-derived cell lines: Mel-DCC-11 (the parental line, sensitive to the BRAF inhibitor) and Mel-DCC-11-R (resistant to the BRAF inhibitor). We employed targeted-panel sequencing to examine the coding sequences of 410 cancer-associated target genes.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-09T11:18:54.487497+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001226","title":"Processing of tissue and cfDNA samples of CRC patients using Active-seq","description":"In this study, we have developed a novel technology called Active-Seq (Azide Click Tagging for In Vitro Epigenomic sequencing), a base conversion-free technology used to profile the DNA methylation status of a sample, based on the isolation of DNA containing unmodified CpG sites using a mutated bacterial methyltransferase enzyme and a synthetically prepared cofactor analogue. \r\n\r\nWe procured samples from colorectal cancer (CRC) patients including tumour tissue as well as normal adjacent tissues. The data enabled us to identify CRC-specific markers that could then be used to track and monitor the presence of tumour DNA in cell-free DNA plasma (cfDNA) samples procured in the same patients. The FASTQ files of all the colorectal cancer tissues, normal adjacent tissues as wells as the cfDNA samples are available in this submission. \r\n\r\nThe data made available in this study have been used to outline an approach for tumour-informed disease profiling in colorectal cancer cfDNA samples using Active-Seq. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-09T12:11:14.508287+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001227","title":"Axes of Biological Variation in Diffuse Large B-Cell Lymphoma ","description":"To explore the DLBCL molecular and genetic environment, we conducted genome-wide NGS sequencing on 103 DLBCL biopsy samples (named as Cornell-NCI cohort) with NGS platforms, including bulk WES, etc. The raw fastq files of the bulk WES were deposited on the EGA for user access. For additional information regarding the genomic data associated with the study, please also see the paper companion website at https://llmpp.ccr.cancer.gov/local/DLBCL_singlecell/","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[41544629],"external_links":null,"is_released":true,"released_date":"2025-11-24T11:38:20.863493+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001228","title":"Epigenomic Rewiring of Transcriptional Regulators by Chromatin Variants Drives Intra-Tumor Heterogeneity and Chemotherapy Resistance in Triple Negative Breast Cancer","description":"Therapeutic resistance in triple-negative breast cancer (TNBC) is closely linked to intra-tumor heterogeneity (ITH) and cellular plasticity. This study profiled matched paclitaxel-sensitive and acquired-resistant patient-derived xenograft (PDX) models of TNBC using single-nucleus multiome sequencing of chromatin accessibility and gene expression. Integrated analysis revealed that epigenomic and transcriptional variation fuels cellular plasticity and supports therapy resistance. Despite pronounced inter-patient heterogeneity, resistance was governed by conserved rewiring of regulatory networks and convergent activation of transcriptional regulators across disease stages. Functional perturbation of a subset of the transcriptional regulators re-sensitized resistant tumors to chemotherapy, highlighting actionable transcriptional dependencies that can constrain tumor evolution. These findings position epigenomic variation at the core of resistance in TNBC and identify shared regulatory vulnerabilities for early and late therapeutic intervention.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001229","title":"Differential Wnt/β-Catenin Signaling Activities Shape Distinct Tumor Cell Phenotypes","description":"By profiling patient-derived hepatoblastoma organoids via single-cell transcriptomics and chromatin dynamics, we identify subtype-specific transcriptional and epigenetic profiles. Using CUT&RUN, we show that β-catenin engages distinct genomic regions, which is dictated by differential association with TCF/LEF family transcription factors. TCF7L2 binds to a motif, distinct from the classical Wnt consensus sequence, which is found in the promoter of hepatic target genes.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-10T11:38:55.758849+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001230","title":"Chromatin accessibility profiling of primary human hepatocytes","description":"The chromatin accessibility profiling of primary human hepatocytes using Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq).","abstract":null,"study_type":"Epigenetics","pubmed_ids":[40452229],"external_links":null,"is_released":true,"released_date":"2025-09-02T16:34:16.469612+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001231","title":"High MAPK Activity Leading to Reduced WNT Signaling Drives Metastasis in Colorectal Cancer","description":"Colorectal cancer, a leading cause of cancer-related mortality due to distant metastases, is driven by activating mutations in the Wnt and MAPK pathways. Understanding the interplay between these crucial pathways during metastatic progression is essential for developing effective treatments. Here we developed an immunocompetent mouse model of metastatic colorectal cancer using in vivo orthotopic passaging. We demonstrate that highly metastatic tumor cells exhibit chromosomal amplifications in MAPK pathway genes, leading to increased MAPK activity, which in turn suppresses Wnt-associated transcriptional programs, including stem cell-associated genes. Inhibiting mutant KrasG12D effectively reversed this metastatic transcriptional state, reducing MAPK-driven gene expression and restoring Wnt activity. Notably, this treatment significantly curtailed lung metastases and reduced liver metastases during early seeding stages. Analysis of CRC patient data revealed that high MAPK activity and the associated metastatic gene signature correlated with poorer survival outcomes. These findings underscore that the plasticity of metastasis-initiating cells in CRC arises from the opposing roles of MAPK and Wnt signaling, despite their synergistic importance in colon tumor initiation. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-03T14:29:07.864684+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001232","title":"The Emirati T2T-level Pangenome: A complete Diploid Graph of 58 Genomes","description":"This study presents a comprehensive Emirati telomere-to-telomere level (T2T) pangenome, constructed from 116 haplotype-resolved assemblies generated from 58 individuals, including 28 trio-based and 30 single-sample assemblies. The assemblies exhibit high contiguity (median 150 Mb) and high consensus accuracy (median QV 59), with 71.9% of chromosomes reaching T2T-level scaffold status. The resulting pangenome graph captures both globally shared and regionally enriched genetic variation, including sequences in complex regions that are inaccessible to less complete assemblies. Comparisons indicate diversity levels comparable to those of the Human Pangenome Reference Consortium, while highlighting unique Emirati genomic features. This reference forms a key resource for human pangenomics and precision medicine in the UAE. This work provides a foundational resource to improve variant discovery and genome annotation, contributing vital diversity data to global pangenomics efforts and enabling precision medicine in the region.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-10T11:17:38.606807+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001233","title":"Emirati Diploid Single Samples Assemblies","description":"This study, as part of the Emirati Genome Project, aims to establish a foundational pangenome reference to advance precision medicine in the United Arab Emirates. We are generating single-sample diploid whole genome assemblies for 30 Emirati nationals using deep PacBio HiFi sequencing. This process yielded 60 distinct assemblies representing both the maternal and paternal genomes for each individual. The resulting high-quality reference will capture the unique genetic landscape of the Emirati population, thereby accelerating translational research and genomic discovery.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-10T11:17:30.528735+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001234","title":"Emirati Phased Diploid Trio-Assemblies","description":"This study, conducted under the Emirati Genome Project, aims to build a foundational pangenome reference to enable precision medicine in the United Arab Emirates. We generated phased diploid genome assemblies for 27 Emirati nationals using deep PacBio HiFi sequencing and a trio-based assembly procedure. In total, this produced 54 haplotype-resolved assemblies representing maternal and paternal genomes for each participant. The resulting high-quality reference captures population-specific genetic diversity and will accelerate translational research, variant interpretation, and genome-informed healthcare in the region.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-10T11:17:33.194208+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001235","title":"Emirati T2T Assembly","description":"This study generates a telomere-to-telomere (T2T) trio-based genome assembly for a female Emirati individual, creating a high-quality reference representative of an understudied population. We produced multi-platform sequencing for a single family trio: PacBio HiFi (>60× per parent, >120× offspring), ONT ultra-long reads (>110× offspring), and Illumina short-read WGS (>100× for all three). The offspring genome was assembled in a trio framework to leverage parental information for accurate phasing and error resolution. Scaffolding and finishing utilized NTLink for initial scaffolding, RagTag for reference-guided refinement, and Quartett for gap filling, resulting in a contiguous, population-relevant assembly suitable for downstream variant discovery and pangenome integration.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-10T11:17:33.194208+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001236","title":"Non-neuronal TGF-β–mediated extracellular matrix remodeling drives neurodegeneration in a PSP-Richardson syndrome model","description":"Progressive supranuclear palsy-Richardson syndrome (PSP-RS) is a devastating neurodegenerative disorder marked by rapid motor decline, cognitive impairment, and widespread accumulation of pathological tau. Yet, the molecular triggers of sporadic PSP-RS remain elusive. In this study, we combined patient-derived midbrain organoids with integrative multi-omics to uncover a previously unrecognized pathological cascade. At the core lies an early and aberrant activation of TGF-β signaling, which initiates profound extracellular matrix (ECM) remodeling and aberrant integrin-mediated focal adhesion. This cascade leads to persistent hyperactivation of PI3K/AKT and MAPK/ERK pathways, disrupting cytoskeletal integrity, impairing autophagy, promoting pathological tau phosphorylation and mislocalization, and ultimately driving synaptic degeneration. Single-cell RNA sequencing revealed an ectopic expansion of vascular leptomeningeal-like cells (VLMCs), a collagen-producing population, accompanied by a broad ECM gene dysregulation unique to PSP-RS. Remarkably, pharmacological blockade of TGF-β, AKT, ERK, or mTOR signaling reversed tau pathology and restored synaptic integrity. These findings position TGF-β-driven ECM remodeling as a master regulator of neurodegeneration in sporadic PSP-RS and unveil multiple actionable therapeutic targets for this currently untreatable disease.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-13T14:28:26.06965+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001237","title":"Transcriptional effect of 4HTBZ on Caco-2 cells","description":"This study was performed to investigate the transcriptional effect of the H2S donor 4HTBZ on intestinal epithelial cells upon inflammatory stimulation. Caco-2/TC7 cells were pre-stimulated with interferon gamma (IFNG, 2.5 ng/mL) and tumor necrosis factor alpha (TNF, 10 ng/mL), followed by treatment with 4HTBZ (50 µM) or vehicle (0.1% DMSO) for 72 hours. Total RNA was extracted using the RNeasy Mini Kit (Qiagen, Hilden, Germany), and cDNA libraries were prepared with the QuantSeq 3′ mRNA-Seq Kit (Lexogen, Inc.) and sequenced on an Illumina HiSeq4000 system.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-08T16:10:32.615139+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001238","title":"Molecular classification of small intestinal adenocarcinomas","description":"In this study we analyzed genomic and transcriptomic data from 135 small intestinal adenocarcinoma (SIA) patients. Through this analysis, we identified three distinct subtypes based on gene expression patterns, revealing the diverse molecular characteristics among SIA patients. Our findings provide comprehensive insights into the unique features of each subtype.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-25T16:07:45.89279+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001239","title":"Whole-exome sequencing data from a phase 2 trial of dasatinib for patients with relapsed or refractory nodal T follicular helper cell lymphomas","description":"Whole-exome sequencing (WES) analysis data from tumor tissues of 14 patients with T follicular helper cell lymphomas enrolled in a phase 2 trial of dasatinib for relapsed or refractory nodal disease.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-16T10:55:03.068725+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001240","title":"Single-cell sequencing data from a phase 2 trial of dasatinib for patients with relapsed or refractory nodal T follicular helper cell lymphomas","description":"Single-cell analysis data of immune cells from peripheral blood samples of 10 patients with T follicular helper cell lymphomas enrolled in a phase 2 trial of dasatinib for relapsed or refractory nodal disease.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-16T10:54:55.937773+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001241","title":"Maturation of Human Intestinal Epithelial Cell Layers Fortifies the Apical Surface against Salmonella Attack","description":"Pathogen invasion of intestinal epithelial cells (IECs) is a key gut infection event. The dynamics of this process in intact epithelia and the factors governing IEC susceptibility remain underexplored. We present a resource for live-cell infection imaging in human enteroid-/colonoid-derived IEC layers, across maturation states and in the presence or absence of soluble mucus production. Utilization of this resource shows how human IEC maturation fortifies the apical surface against invasion by Salmonella Typhimurium (S.Tm). Immature IEC layers appear permissive to S.Tm invasion, but maturation towards an enterocyte/colonocyte phenotype reduces the susceptibility by up to tenfold. This shift couples to downregulated expression of actin regulatory proteins exploited by the pathogen, an increased dependence on the S.Tm effector SipA, and the build-up of the apical IEC glycocalyx linked to surface-attached mucins like MUC13 and nullifiable by StcE-enzyme treatment. This underscores how the maturation state of human IECs governs susceptibility to bacterial invasion.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-25T09:21:59.790332+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001242","title":"Visium CytAssist Spatial Gene Expression analysis for FFPE glioblastoma samples","description":"This study used spatial transcriptomics to investigate gene expression patterns in FFPE glioblastoma tumor samples from four patients.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-19T14:26:11.447544+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001243","title":"Bevacizumab plus erlotinib in advanced solid cancers with Krebs cycle gene mutations: A multicenter phase II study","description":"Targeting aberrant metabolism in tumors with alterations in genes encoding Krebs cycle enzymes, a central component of glucose metabolism, is a promising therapeutic strategy. These tumors rely on aerobic glycolysis and promote VEGF-dependent angiogenesis; furthermore, EGFR signaling enhances aerobic glycolysis. This phase 2 trial evaluated bevacizumab and erlotinib in patients with solid tumors harboring Krebs cycle gene mutations.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-15T14:28:45.060075+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001244","title":"Raw fastq files (not trimmed) from RNAseq sequencing","description":"Samples from infants diagnosed with KMT2A-r B-ALL confirmed by comprehensive immunophenotypic and molecular/cytogenetic features. Mononuclear cells containing >87% blasts were isolated by density gradient centrifugation. Immunophenotyping was performed using the monoclonal antibodies CD45-FITC, CD19-APC, and NG2-PE.  NG2POS (NG2 positive) and NG2NEG (NG2 Negative) B-ALL blasts (CD45dimCD19+) were sorted by fluorescence-activated cell sorting (FACS) using a FACS-Aria Fusion cell sorter (BD Biosciences). ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-26T13:47:11.187444+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001245","title":"RNA sequencing of neuroblastoma PDX models under treatment","description":"This study investigates how transcriptional noise contributes to phenotypic plasticity in pediatric cancers using a neuroblastoma patient-derived xenograft (PDX) model. Phenotypic plasticity is a hallmark of cancer that drives heterogeneity and therapy resistance, but the molecular mechanisms remain poorly defined. To probe this, bulk RNA-seq was performed on PDX (IC-pPDX-112) derived cells treated ex vivo with IdU, TGF-β, or their combination in biological triplicates. These RNA-seq data provide a transcriptional profile of how such perturbations modulate gene expression variability and cell state dynamics, serving as a resource for understanding noise-associated plasticity in neuroblastoma.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001246","title":"Clonal Evolution of Neuroblastoma PDX","description":"Neuroblastoma is an aggressive pediatric cancer characterized by poor outcomes in high-risk cases, in part due to extensive intra-tumoral heterogeneity (ITH). To investigate the origins and dynamics of ITH, we performed ultra-low depth single-cell whole-genome DNA sequencing (scDNA-seq) on 9,410 tumor cells from 14 patient-derived xenograft (PDX) models and 4 primary biopsies collected at diagnosis, progression, or relapse. These analyses revealed both monoclonal and polyclonal clonal architectures, with established driver alterations detected as early clonal events. In addition, bulk whole-exome sequencing (WES) was carried out on 6 PDX models subjected to targeted therapy, chemotherapy, or combination treatment to examine clone-specific responses and parallel copy number evolution. Together, these data provide insight into the timing and mechanisms of clonal evolution in neuroblastoma.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001247","title":"DNTR sequencing data of paediatric acute lymphoblastic leukemia","description":"This study used the DNTR-seq method in leukaemia samples to profile the whole-genome and mRNA jointly in single cells. Direct tagmentation is used in a collection of single-cell whole genome sequencing (scWGS) methods, including DNTR-seq, which provide high quality data at ultra-low to low coverage.\r\n\r\nThe overall goal was to characterize the genetic and transcriptional heterogeneity of cancer samples. To infer clonal structure and evolutionary history, copy number analysis based workflows were implemented.\r\n\r\nBone marrow mononuclear cells from pediatric acute lymphoblastic leukemia samples were FACS sorted into 384 plates to generate the DNA and RNA profiles.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-16T17:10:19.627217+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001248","title":"Whole exome sequencing of bladder tumors","description":"Bladder carcinomas are immunogenic, and patients with bladder cancer benefit from\r\nimmune checkpoint therapy. This is correlated to a high tumor mutation burden, which provides a\r\nhigher number of neoepitopes that can be recognized by tumor-specific CD8+ T cells. Intravesical\r\nBacillus Calmette-Guérin (BCG) is used to treat non-muscle invasive bladder cancer (NMIBC), but its\r\nmechanism of action remains elusive. Most lymphocytes appearing in the urine of BCG-treated patients\r\nare CD4+ T cells though preclinical studies showed that CD8+ T cells are also necessary for BCG\r\ntreatment efficacy. It is currently unknown which proportion of patients with non-metastatic bladder\r\ncancer develop a spontaneous antitumor CD8+ response, and if BCG treatment influences this response.\r\nwere prepared using the xGen Dual Index UMI Adapters\r\n(IDT), and genomic DNA (gDNA) extracted (DNeasy kit, Qiagen) from formalin-fixed paraffin-\r\nembedded (FFPE) or snap-frozen tumor tissue, as well as autologous lymphocytes. Libraries were\r\nsubjected to paired-end sequencing using Illumina HiSeq4000 with a coverage depth of 250X.\r\nLibrary preparation was carried out with the AllType FASTplex NGS 11 Loci Flex Kit (One Lambda),\r\nand sequencing was conducted on the Illumina MiSeq platform.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[41312368],"external_links":null,"is_released":true,"released_date":"2025-11-07T15:13:37.248534+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001249","title":"Whole Exome Sequencing of Waldenström Macroglobulinemia (WM) Precursor Conditions","description":"In this study we aimed to comprehensively characterize the genomic landscape of WM precursor conditions and identify potential biomarkers of progression to symptomatic WM by means of Whole Exome Sequencing (WES) of CD19-selected samples from 139 patients, primarily  with IgM-MGUS and asymptomatic WM. Overall, our study shows that genomic profiling of patients’ tumor at the time of aWM diagnosis might represent an improved strategy for identifying patients at high risk to progression who could benefit from earlier intervention.\r\n","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-08T12:03:19.560842+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001250","title":"Single-cell chromatin accessibility profiling reveals ecDNA-driven epigenetic heterogeneity and tumor aggressiveness in primary glioblastoma ","description":"In this study, we applied single-cell ATAC-seq profiling to primary glioblastoma (GBM) tumors to investigate the chromatin accessibility landscape shaped by ecDNA. Our analysis revealed that ecDNA drives both intertumoral and intratumoral epigenetic heterogeneity in GBM. We further demonstrated the widespread distribution of ecDNA-positive cells within ecDNA-harboring tumors and their role in facilitating oncogenic transcription factor binding at ecDNA-specific accessible chromatin regions. In addition, we demonstrated that cancer stem cells in primary ecDNA-harboring tumors preferentially harbor ecDNA, functioning as self-renewing reservoirs that sustain a high ecDNA burden.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001251","title":"Identify cancer stem cells (CSCs) from primary GBM tumors","description":"In this study, we integrated single-cell ATAC-seq profiles from primary GBM tumors and patient-derived GSC cultures to identify CSCs from the primary tumors. We revealed that CSCs preferentially harbor ecDNA serve as a renewable reservoir, sustaining a high ecDNA burden and driving intratumoral heterogeneity.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001252","title":"Co-culture experiment (hashed samples)","description":"The principles governing tissue architecture and the mechanisms underlying its disruption in disease remain poorly understood. Here, we utilized single-cell and spatial mapping to interrogate the mechanisms directing immune cell organization in human lymph nodes and its disruption in architecturally distinct lymphoma entities: indolent follicular lymphoma (FL) and aggressive diffuse large B cell lymphoma (DLBCL). Our data substantiate the central role of lymph node stromal cells in chemokine-driven lymphocyte zonation and reveal an inflammatory feedback loop fueled by tumor-reactive T cells, triggering stromal remodeling, progressive loss of homeostatic chemokine gradients and tissue organization from non-malignant to FL and DLBCL. Loss of homeostatic chemokines was associated with adverse patient survival, identifying the underlying architectural rearrangement as a key event during lymphomagenesis. Collectively, our results highlight the principles of lymph node organization and suggest how lymphoma-induced microenvironmental reprogramming drives loss of tissue organization.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-02T11:56:40.536375+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001253","title":"Transcriptomic analysis of membranes from proliferative vitreoretinal diseases and isolated human retinal pigment epithelium","description":"This study investigates the transcriptomic profiles of proliferative vitreoretinal diseases (PVD) membranes, including proliferative vitreoretinopathy and epiretinal membranes collected from patients undergoing surgery, as well as human retinal pigment epithelial cells isolated from post-mortem donor eyes.\r\nTotal RNA was extracted using AllPrep DNA/RNA Micro Kit (Qiagen) and cDNA libraries were prepared using the Ovation Solo RNA-seq Kit (Tecan). Multiplexed libraries were loaded onto a NovaSeq 6000 platform (Illumina), and sequences were generated using a 200-cycle kit.\r\nThis study includes over 80 pathological and healthy samples to allow comparison of gene expression profiles and gain insights into the molecular mechanisms of PVD.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-12T12:38:34.628664+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001254","title":"BCL11B Enhancer Hijacking by t(14;16)(q32;q24) Translocation Defines a Novel High-Risk Subtype of T-ALL","description":"We performed integrated analysis of pediatric and adult T-ALL and mixed phenotype acute leukemias (MPALs) by whole-genome and whole-transcriptome sequencing. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-23T16:01:27.401217+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001255","title":"Deregulation of FOXF1/FENDRR from t(14;16)(q32;q24) defines a subtype of high risk lineage ambiguous leukemia","description":"Despite great progress in understanding the genomic basis of immature T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL) and acute leukemias of ambiguous lineage (ALAL), there are still cases that lack defining genetic markers, complicating risk stratification and limiting targeted therapeutic options. Here, we describe a subtype of leukemia defined by the t(14;16)(q32;q24) translocation, which places the FOXF1 gene and its antisense long noncoding RNA gene FENDRR under the regulatory control of the BCL11B enhancer, leading to their ectopic transcriptional activation. Analysis of different high-throughput sequencing data, including WGS, RNA-seq, scDNA-seq, scRNA-seq, ChIP-seq, ATAC-seq, and HiChIP-seq, identified BCL11B-enhancer mediated deregulation of FOXF1/FENDRR as a hallmark of a subtype of high-risk lineage ambiguous leukemia that is potentially amenable to targeted therapeutic intervention.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-06T11:41:40.43218+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001256","title":"Patterns of hypermutation shape gliomagenesis and immunotherapy response in mismatch repair deficient glioma","description":"Primary mismatch-repair deficient (priMMRD) gliomas are lethal tumours characterized by hypermutation, resistance to chemoradiation, and variable response to immunotherapy. To investigate the mechanisms governing the emergence of driver mutations and their impact on gliomagenesis and outcome, we analyzed genomic and clinical data of 162 priMMRD gliomas. We identified three subgroups defined by secondary driver mutations in replicative DNA polymerases or IDH1. These subgroups converge on glioma drivers through distinct combinations of genomic instability-generating mechanisms, displaying an inverse correlation between point mutation and copy number alteration. MMRD signatures drive the emergence of specific mutations in TP53 and IDH1, notably excluding common pediatric glioma drivers. Global hypomethylation stratifies priMMRD gliomas into a unique methylation cluster. DNA-polymerase mutant priMMRD gliomas exhibit ultrahypermutation, an immune-hot microenvironment, and immunotherapy responsiveness, whereas IDH1mut priMMRD gliomas are immune-cold and immunotherapy resistant. MMRD-driven gliomagenesis defines the role of non-random mutagenesis-patterns in cancer development, providing frameworks for targeted and immune-therapeutics.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001257","title":"Whole genome sequencing data of pediatric TCF3::PBX1 acute lymphoblastic leukemia","description":"TCF3::PBX1 leukemia is a rare subtype of B-cell acute lymphoblastic leukemia (B-ALL), occurring in approximately 3–5% of pediatric cases. It results from a chromosomal translocation t(1;19)(q23;p13), generating the TCF3::PBX1 fusion gene, which disrupts normal transcriptional regulation and contributes to leukemogenesis. Although historically associated with poor prognosis, contemporary risk stratification and intensified therapy have significantly improved outcomes, and both 5-years DFS and OS are nowadays ≥ 0.96.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-15T15:20:41.320443+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001258","title":"Genetic and Microenvironmental Analysis of Peripheral T-cell Lymphoma","description":"This study enrolled 129 patients diagnosed with PTCL, comprising 94 cases of nTFHL and 35 cases of PTCL-NOS. Whole exome sequencing (WES) and RNA sequencing (RNA-seq) were performed using DNA and RNA of sufficient quality extracted from their tumor specimens. WES was conducted for all 129 cases, while RNA-seq was performed on 57 tumor samples.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-06T10:14:51.590164+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001259","title":"Identification of putative multiple myeloma (MM) susceptibility genes","description":"We sought to identify novel MM susceptibility genes using a collection of families with multiple cases of MM/MGUS, including 189 affected individuals from 40 families, and index cases from an additional 88 families, along with 170 early-onset (EO) MM cases (≤ 55 years). We analyzed a total of 347 affected individuals using whole exome (N=321) and whole genome (N=26) sequencing. Samples were identified and collected through nation-wide efforts in France, Sweden and Greece. We focused on rare (MAF<0.5%) germline protein truncating and likely deleterious missense variants in genes harboring variants in at least two families showing variant-disease segregation, and in additional index (≥2) and/or early-onset (≥2) cases.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-02T12:07:01.445236+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001260","title":"Innate immune cell subsets are enriched in synovial fluid of ACPA-negative rheumatoid arthritis and characterised by distinct type I IFN gene signatures","description":"This study provides a detailed comparison of the myeloid\r\ncell landscape in the SF of patients with ACPA+ and\r\nACPA− RA, highlighting the unique involvement of type I\r\nIFN responses in ACPA− RA.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-16T17:06:34.608537+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001261","title":"ChIP-seq of CRC samples","description":"The aim of this study was to elucidate the intricate manifestations and contributory mechanisms of TCA cycle rewiring in colorectal carcinogenesis. We identified a splicing isoform of citrate synthase (CS), CS-ΔEx4, and unveiled its role in TCA cycle dysregulation in colorectal cancer (CRC).  This study discovered the presence of a spliced CS isoform that promotes CRC progression and identified a molecule that holds potential for targeting the CS-ΔEx4 and CS-FL heterocomplex.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001262","title":"16S rRNA Rectal Mucus","description":"16S rRNA sequencing of rectal mucus samples from patients suspected to have colorectal cancer. This is 1 of 4 sequencing experiments on the same sample type.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-16T10:31:05.46888+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001263","title":"Parkinson’s disease as a programmed process of accelerated aging","description":"This study investigates the molecular origins of sporadic Parkinson's disease (sPD) under the hypothesis that it is an intrinsic, programmed process of accelerated cellular aging. Using a longitudinal patient-derived hiPSC model, we generated high-resolution, whole-genome maps of the epigenetic landscape, including 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). By comparing the epigenomes of neural progenitors at an early, asymptomatic stage with those from a later, pathologically relevant stage, we aim to identify the dynamic epigenetic changes that drive disease-associated transcriptional programs and the accelerated aging trajectory.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001264","title":"Human non-malignant plasma cfRNA study - raw data","description":"mRNA capture sequencing on plasma sample from 88 patients with a non-malignant disease and from 37 healthy donors.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-19T14:16:26.458501+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001265","title":"Human prostate cancer plasma cfRNA study - raw data","description":"mRNA capture sequencing on plasma sample from 132 prostate cancer patients and 48 control donors.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-19T14:16:24.935739+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001266","title":"Identification of SOX2 binding at ecDNA-specific accessible regions","description":"We here performed SOX2 ChIP-seq in G523_L and detected SOX2 binding at a prominent ecDNA-specific enhancer marked by H3K27ac and CTCF, consistent with active regulatory function and chromatin loop anchoring.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001267","title":"Multimodal epigenetic sequencing analysis of cell-free DNA identifies biomarkers for ALS diagnosis and progression","description":"The role of the circulating epigenome in ALS remains understudied. We aim to develop diagnostic and prognostic blood-based biomarkers for Amyotrophic Lateral Sclerosis (ALS) by profiling methylome signatures in circulating cell-free DNA (cfDNA) in 20 sporadic ALS cases, 10 C9orf72-associated ALS cases, 10 asymptomatic C9orf72 expansion carriers, and 21 healthy controls using targeted enzymatic methyl-sequencing (EM-seq) of ~4 million CpG loci. We detected numerous differentially methylated genes, including several implicated in ALS risk and pathobiology, and integrated multiple epigenetic features with our Multimodal Epigenetic Sequencing Analysis (MESA) algorithm, achieving an ROC AUC of 0.91 and detecting ~70% of ALS cases at ~100% specificity. Methylation at a subset of loci also correlated with clinical progression and cerebrospinal-fluid neurofilament levels, supporting the potential of cfDNA-based biomarkers for ALS diagnosis and monitoring.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-10T17:57:09.603183+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001268","title":"mtscATAC-seq of immune cells from healthy donors over age","description":"Mitochondria are essential for cellular energy metabolism and carry their own multi-copy genome. As we age, somatic mutations accumulate in the mitochondrial genome (mtDNA) which has been associated with mitochondrial dysfunction contributing to aging and associated disorders. A quantitative understanding of the rate of acquisition of somatic mtDNA mutations during aging, their distribution across cell types as well as their phenotypic impact, in human organ systems is however only emerging. To systematically characterize this, we profiled >425,000 human immune cells from cord blood, peripheral blood, and bone marrow from donors of different ages via mitochondrial single-cell ATAC-sequencing (mtscATAC-seq).","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001269","title":"Immune Biomarkers in Metastatic Castration-resistant Prostate Cancer","description":"Background: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease in which molecular stratification is needed to improve clinical outcomes. The identification of predictive biomarkers can have a major impact on the care of these patients, but the availability of metastatic tissue samples for research in this setting is limited.\r\nObjective: To study the prevalence of immune biomarkers of potential clinical utility to immunotherapy in mCRPC by tumour RNA sequencing, and to determine their association with overall survival (OS).","abstract":null,"study_type":"RNASeq","pubmed_ids":[35491356],"external_links":null,"is_released":true,"released_date":"2025-09-18T12:13:07.111718+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001270","title":"Dynamics of checkpoint receptors in γδ T cell subsets are associated with clinical responses during anti-PD-1 immunotherapies","description":"Gamma delta (γδ) T cells are innate-like lymphocytes with potent anti-tumor properties. Herein, we show that immune checkpoint receptors (ICRs) display differential expression and regulation by the JAK-STAT pathway in Vδ1 and Vδ2 cells and identify constitutive (e.g. TIGIT, PD-1) and inducible (e.g. TIM-3, LAG-3, CTLA-4) ICRs. In melanoma, all γδ T cell subsets downregulated AP-1 transcription factors, but Vδ1 cells specifically expressed high levels of ICR, TOX and inhibitory killer Ig-like receptor (KIR) transcripts, reminiscent of exhaustion. However, patient-derived cells were functionally competent, although induction of LAG-3 and CTLA-4 was impaired. During anti-PD-1 monotherapy, Vδ1 cells specifically bound high levels of therapeutic antibody but only in patients who responded to treatment, revealing a potential new prognostic marker for evaluating the efficacy of IC blockade (ICB) therapy. Finally, expression of KIR genes in Vδ1 cells was downregulated in response to successful ICB therapy. Collectively, our data indicate an intricate relationship between ICRs and γδ T cells and reveal novel approaches by which these cells can be harnessed in order to discern or improve cancer immunotherapy.             ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-19T09:54:49.329796+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001271","title":"Broad utility of ultrasensitive analysis of ctDNA dynamics across solid tumors treated with immunotherapy","description":"Plasma ctDNA sequencing data from samples collected from a pan-cancer cohort of patients with advanced-stage disease treated with IO therapies. This study highlights the broader applicability of ultrasensitive ctDNA as a biomarker across cancer types and immunotherapy modalities. Here, we applied a whole-genome, tumor-informed approach to study ctDNA in 202 advanced-stage cancer patients treated at VHIO. This study captures the plasma sequencing data from the project.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-25T20:56:03.268538+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001272","title":"Non-small cell lung cancer molecular subtypes and vulnerability to immunotherapy treatment combinations","description":"The phase 3 IMpower150 trial in treatment-naïve patients with metastatic non-small-cell lung\r\ncancer (NSCLC) demonstrated significantly longer progression-free (PFS) and overall survival\r\n(OS) with first-line atezolizumab (anti-PD-L1)-bevacizumab (anti-VEGF)-carboplatin-paclitaxel\r\n(ABCP) than with bevacizumab-carboplatin-paclitaxel (BCP). We characterised four molecular\r\nNSCLC subtypes identified by unsupervised clustering of transcriptomes of 564 pre-treatment\r\nprimary tumour samples from IMpower150 using non-negative matrix factorization (NMF1-4).\r\nEach subtype had distinct tumour PD-L1 expression levels, epithelial characteristics, immune\r\ncomposition, and treatment outcomes. Both NMF2 (enriched in tumour proliferation signal,\r\nmacrophages, and monocytes) and NMF4 (enriched in B-cells and T cells) had elevated tumour\r\nPD-L1 expression. Of these two, only NMF4 demonstrated PFS and OS benefits with ABCP\r\nversus either BCP or atezolizumab-carboplatin-paclitaxel (ACP). Patients with NMF1 (enriched\r\nin basal and squamous-like cells) had improved outcomes on ABCP compared with ACP or\r\nBCP; those with NMF3 (enriched in adenocarcinoma signatures) showed similar outcomes\r\namong treatments. These insights could help inform individualised first-line treatment for\r\nmetastatic NSCLC.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-14T16:05:37.001176+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001273","title":"DNA Replication Speed controls Epigenome Integrity and T Cell Fate","description":"Epigenetic mechanisms maintain cellular identities by enforcing stable, cell type-specific transcriptional programs while also allowing regulated plasticity for adaptations to environmental cues like differentiation signals. Dysregulation of this dual capacity has been linked to cancer and chronic inflammation, with the regulatory mechanisms remaining poorly understood. Here, we identify DNA replication speed as a physiological regulator controlling epigenome stability and plasticity. Using T-lymphocytes as a model, we demonstrate that fast DNA replication speed impaired epigenome stability, causing DNA methylation maintenance errors at cell type-specific enhancers and heterochromatin, ultimately leading to compromised cell function. However, accelerated DNA replication speed supported epigenome plasticity during differentiation, promoting successful cell-type transitions","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-16T17:45:16.353778+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001274","title":"ChIP sequencing for β-catenin and histone modifications in HCC cell lines and organoids with CTNNB1 mutations","description":"CTNNB1 mutation is a major driver of HCC, particularly in metabolic-associated subtype. This study utilized patient-derived tumour organoids and cell lines harbouring various endogenous CTNNB1 mutations to comprehensively map the transcriptional repertoire regulated by mutant β-catenin through ChIP-seq under normal and fatty conditions. Genome-wide binding patterns of β-catenin were integrated with ChIP-seq data for histone modifications H3K27ac and H3K27me3 to assess active and repressive chromatin states. Oleic acid treatment was used to model fatty conditions.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-22T08:46:48.350601+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001275","title":"Heritable pulmonary arterial hypertension - new genetic findings and environmental triggers ","description":"Whole exome seqeuncing data were analysed for a total of 13 family members of five heritable pulmonary arterial hypertension (HPAH) families to identify a disease causing variant. In a first step, variants only present in affected family members and absent in healthy relatives of the respective family were selected. Subseqeuntly, due to incomplete penetrance of genes in PAH, the analysis was extended to variants present both in affected and healthy individuals. Heterozygous variants were primarily investigated followed by homozygous, compound heterozygous, and bi-allelic variants of interest. This study led to the identification of rare deleterious variants in three out of five families. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-25T10:02:22.625621+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001276","title":"Transcriptome profiling of megakaryocytes and platelets: application to GP9- and IKZF5-related thrombocytopenia ","description":"Platelets are anucleate cells produced in the bone marrow and derived from large progenitor cells called megakaryocytes (MKs). Platelets receive RNA transcripts from their progenitorial MKs during thrombopoiesis. However, the correspondence between platelet and MK transcriptomes is poorly understood, particularly in the context of germline mutations that cause platelet formation defects or thrombocytopenia. We have studied the effects of two such mutations on MK and platelet transcriptomes. We generated immortalized MK cell line (imMKCL)-based models of Bernard-Soulier syndrome and IKZF5-related thrombocytopenia. MKs derived from imMKCLs with either a homozygous deletion of GP9 (GP9-/-) or a heterozygous Y121F variant in IKZF5 (IKZF5WT/Y121F) exhibited reduced proplatelet formation (reductions of 96% and 57%, respectively). Platelets from patients with either GP9-/- or IKZF5WT/Y121F genotypes had broad transcriptomic dysregulation, suggesting that (pro)platelet formation defects due to mutations in glycoprotein receptor and transcription factor genes such as GP9 and IKZF5 affect the trafficking of transcripts from MKs into platelets. RNA-seq data from MKs at four stages of differentiation revealed widespread but distinct changes in expression over time between the GP9-/- and the IKZF5WT/Y121F genotypes. Dysregulated genes in GP9-/- MKs were enriched for RNA metabolism and actin/tubulin folding pathways while those in IKZF5WT/Y121F MKs were enriched for cell cycle pathways. Most of these genes were also dysregulated in the platelets of patients with the corresponding diseases. Our results suggest that patients with inherited forms of thrombocytopenia present with a transcript trafficking defect during platelet formation. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-30T12:01:33.401893+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001277","title":"Circulating cell-free DNA methylation profiles as noninvasive multiple sclerosis biomarkers: A proof-of-concept study","description":"In chronic neurodegenerative diseases such as multiple sclerosis (MS), there is a critical unmet need for cost-effective non-invasive blood biomarkers to concurrently classify disease subtypes, monitor disability severity, and predict long-term progression. In this proof-of-concept study, we performed low-coverage whole-genome bisulfite sequencing (WGBS) on 75 plasma cell-free DNA (cfDNA) samples collected from a well-characterized real-world prospective clinic cohort with longitudinal disability outcome measurements. We assessed the clinical utility of cfDNA methylation profile for differentiating MS patients from non-MS controls, classifying MS subtypes, estimating disability severity, and predicting disease trajectories. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[40034794],"external_links":null,"is_released":true,"released_date":"2026-07-17T08:45:49.084833+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001278","title":"Long-read single-cell genome, transcriptome and open chromatin profiling links genotype to phenotypes","description":"Current single-cell multiomics methods typically provide limited genomic information, constraining genotype-phenotype studies. To address this gap, we developed SPLONGGET (Single-cell Profiling of LONG-read Genome, Epigenome, and Transcriptome), which integrates 10X Genomics barcoding with Oxford Nanopore sequencing to simultaneously profile genome, chromatin accessibility, and full-length transcriptomes in thousands of single cells. By retaining all tagmentation fragments during library preparation, SPLONGGET delivers whole-genome coverage, supports target enrichment for effective single-cell genotyping, and remains backwards compatible with existing short-read workflows. We apply SPLONGGET to longitudinal samples from a case of pediatric B-cell acute lymphoblastic leukemia (B-ALL) to reveal clonal dynamics during therapy and the phenotypic effects of somatic variation, providing valuable insights into disease progression and relapse. In conclusion, SPLONGGET enables integrated high-throughput analysis of genetic variation and molecular phenotypes using off-the-shelf kits, offering a timely and powerful tool to study genetically heterogeneous samples, such as tumours but also ageing normal tissues.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-25T17:49:05.872668+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001279","title":"Flexible and rapid validation of structural variants using adaptive sampling ","description":"The goal of the study is to confirm and further characterize structural variants and complex genomic rearrangements using adaptive sampling with Oxford Nanopore Sequencing.  Individuals with known structural variants were included in the study and the known rearrangement regions were targeted in the sequencing experiments. In addition to long-read coverage over the targeted regions (around 25X coverage), the rest of the genome is covered by short off-target reads (around 5X coverage). ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-20T16:51:24.522142+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001280","title":"Identification of New Therapeutic Targets for Renal Medullary Carcinoma via Integrated Genomic and Transcriptomic Profiling","description":"Renal medullary carcinoma (RMC) is a rare, aggressive kidney cancer associated with sickle cell trait, characterized by SMARCB1 loss and resistance to conventional therapies used for other renal cell carcinomas (RCC). We conducted whole exome sequencing (WES) on RMC samples. This study provides a large molecular characterization of RMC, highlighting TROP2 and other cell surface markers as promising therapeutic targets. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-08T18:01:24.50578+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001281","title":"PREDICT: PREcision meDicine In ColorecTal cancer: new clinical-genomic network for expanding tailored oncologic care","description":"Analysis of transcriptomics data to study intratumoral heterogeneity in colorectal cancer (CRC), analyzing tumor and normal tissues from the same patients","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001282","title":"Vascularized human retinal organoids, single nucleus","description":"Single nucleus RNA sequencing of human retinal organoids that have been vascularized. Assesses the impact of vascularization on cell types and their gene expression.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001283","title":"A Novel APP p.V742L variant in a patient with ischemic small vessel disease enhances FE65 signalling","description":"We identified a novel variant in the APP gene associated with cerebral ischemic strokes, which is not seen before with APP variants. This results in increased affinity of APP for FE65, APP’s most important intracellular interactor that regulates gene transcription.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-06T21:15:12.867442+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001284","title":"Molecular landscape of C1498 cells","description":"We characterized the genomic background of C1498 cells by whole genome sequencing analysis.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-01T09:57:09.321026+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001285","title":"Circulating kidney injury molecule-1 (KIM-1) and association with response to adjuvant immunotherapy in renal cell carcinoma","description":"Adjuvant immunotherapy is currently the standard of care for patients with resected renal cell carcinoma (RCC) at increased risk of recurrence, but there are no biomarkers available to guide treatment decisions. Kidney injury molecule-1 (KIM-1) has previously been described as a potential circulating biomarker in renal cell carcinoma. We evaluated biomarkers and outcomes among patients who participated in a randomized phase III trial of adjuvant atezolizumab versus placebo in resected RCC (IMmotion010). This trial did not meet its primary DFS endpoint in the intention-to-treat population. An affinity-based proximity extension proteomics assay was used to compare levels of circulating proteins among baseline (post-nephrectomy) serum samples and also with samples taken at time of recurrence. We demonstrate that serum KIM-1 was the most significantly enriched protein at recurrence versus baseline. Patients with serum KIM-1high at baseline had worse disease-free survival (DFS) (hazard ratio 1.68, 95% CI 1.35-2.09), but also had improved DFS when treated with adjuvant atezolizumab versus placebo (hazard ratio 0.72, 95% CI 0.52-0.99). An increase in KIM-1 during follow-up was associated with worse DFS compared to patients with no increase in KIM-1. Comparison of transcriptomic expression profiles in paired primary and recurrent tumor samples revealed that metastatic recurrence is associated with upregulation of transcriptional programs associated with tumor proliferation and myeloid immune suppression. Downregulation of an MHC class I signature was seen among patients with recurrence after treatment with atezolizumab but not placebo, suggesting this is a mechanism of resistance to PD-L1 immunotherapy. These analyses suggest that elevated post-nephrectomy serum KIM-1 enriches for benefit from adjuvant immunotherapy in RCC, and that biomarker driven adjuvant therapy should be evaluated as a potential new paradigm in RCC trials.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-08T09:26:26.36219+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001286","title":"Cell-Free DNA Fragmentation Distinguish Immunotherapy Responders from Non- Responders in Head and Neck Cancer: A Multi-Institute Prospective Study","description":"We performed whole-genome sequencing of 185 plasma cfDNA samples from 68 patients with head and neck squamous cell carcinoma (HNSCC) enrolled in a phase II clinical trial of neoadjuvant and adjuvant pembrolizumab. Using these data, we developed the regional motif diversity score (rMDS), a novel fragmentomic biomarker that predicts immunotherapy response and outperforms established cfDNA metrics.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-10T11:40:09.111171+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001287","title":"Complex genotype-phenotype relationships shape the response to treatment of Down Syndrome Childhood Acute Lymphoblastic Leukaemia","description":"Extensive genetic and epigenetic variegation has been demonstrated in many malignancies. Importantly, their interplay has the potential to contribute to disease progression and treatment resistance. To shed light on the complex relationships between these different sources of intra-tumour heterogeneity, we explored their relative contributions to the evolutionary dynamics of Acute Lymphoblastic Leukaemia (ALL) in children with Down syndrome, which has particularly poor prognosis. We quantified the tumour propagating potential of genetically distinct sub-clones using serial transplantation assays and SNP-arrays. While most leukaemias were characterized by a single dominant subclone, others were highly heterogeneous. Importantly, we provide clear and direct evidence that genotypes and phenotypes with functional relevance to leukemic progression and treatment resistance can co-segregate within the disease. Hence, individual genetic lesions can be restricted to well-defined cell immunophenotypes, corresponding to different stages of the leukemic differentiation hierarchy and varied proliferation potentials. As a result of this difference in fitness, which can be accurately quantified via competitive transplantation assays, matching diagnostic, post-treatment, and relapse leukaemias can be dominated by different genotypes, including pre-leukemic clones persisting throughout the disease progression and treatment. Intriguingly, plasticity also appears to be a temporally defined property that can segregate with genotype. These results suggest that Down Syndrome ALL should be viewed as a complex matrix of cells exhibiting genetic and epigenetic heterogeneity that foster extensive clonal evolution and competition. Therapeutic intervention reshapes this ‘eco-system’ and may provide the right conditions for the preferential expansion of selected compartments and subsequently relapse.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-14T12:29:54.074597+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001288","title":"Delineating pediatric brain tumor progression using single-nuclei sequencing","description":"Pediatric brain cancers are the most common solid tumors in children with varying survival rates depending on molecular features of cancer cells and associated microenvironment. Several studies have used single-cell RNA sequencing to define transcriptional programs active in cancer cells and highlighted supportive roles of non-cancerous cells embedded in these tumors. Although application of single-cell RNA sequencing technology has expanded our understanding of intratumoral heterogeneity and underlying transcriptional mechanisms in brain tumors at diagnosis, mechanisms of disease remains elusive. Therefore, the purpose of this proposal is to characterize cellular and transcriptional states of malignant and non-malignant compartments at primary diagnosis and at relapse. In this study, we performed single-nuclei sequencing of 42 patient samples taken at various disease stages (initial diagnosis, progressive disease, and relapsed disease) from 20 patients with low-grade glioma or Atypical Teratoid Rhabdoid Tumor (ATRT). Bulk whole genome and RNA-seq data for these samples are available from the Children’s Brain Tumor Network and the Gabriella Miller Kids First Data Resource Center. Findings from our study will help define the mechanistic shifts of tumor and non-cancerous cells over course of disease progression. Collectively with the single-cell Pediatric Cancer Atlas funded, this project lays the foundation of an important data set focused on lethal relapsed cancers that can continue to be expanded to identify cancer-intrinsic and extrinsic microenvironmental factors supporting recurrence of pediatric brain tumors.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-02T19:02:34.067033+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001289","title":"Spatial map of microglia states across CNS diseases","description":"Microglia are the key immune cells involved in virtually all diseases of the central nervous system (CNS). Here, we generated a novel large-scale single-cell RNA-sequencing-derived taxonomy through the analysis of > 1 million CNS cells enriched for myeloid cells across > 15 different pathologies and conditions. Disease-associated human microglia, together with CNS-associated macrophages and monocytes, were differentiated iteratively into 27 superclusters and 192 clusters. This top-down approach, in combination with targeted and genome-wide subcellular spatial transcriptomics, enabled us to examine and compare the spatial interactome of the identified superclusters and clusters within and across pathologies. Our data provide new insights into the spatial dynamics of the endogenous CNS immune system during development, health and disease in humans. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-23T15:04:46.867415+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001290","title":"Long-read single-cell RNA sequencing uncovers cell-type specific transcript regulation in COVID-19","description":"SARS-CoV-2 infection leads to extensive host transcriptomic changes, but the role of alternative splicing in shaping the immune response remains underexplored. Here, we present the first application of long-read single-cell RNA sequencing on nasopharyngeal swabs from COVID-19 patients and healthy controls to resolve transcript-level changes across cell types. Leveraging the strengths of long-read sequencing, we characterize alterations in both gene and isoform expression within cell populations of the upper respiratory tract—the primary site of SARS-CoV-2 entry. This approach provides new insights into how transcriptional regulation and splicing shape host immune responses to viral infection.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-16T09:07:32.12097+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001291","title":"Truncated FOS impairs osteogenic differentiation and induces prostaglandin and NFkB signalling in an in vitro cell-of-origin model for osteoid osteoma and osteoblastoma","description":"The effect of FOS truncation on osteogenic differentiation and proliferation was investigated in an in vitro model for osteoid osteoma and osteoblastoma. In this model, truncated FOS (FOSΔ) was overexpressed in human foetal mesenchymal stem cells through a lentiviral vector. Osteogenic differentiation - assessed by measuring mineralization, ALPL expression and ALP activity - and proliferation rate were reduced in cells overexpressing FOSΔ compared to mesenchymal stem cells with an empty lentiviral vector (pLV). Transcriptome-sequencing and differential gene expression analysis revealed decreased gene expression of genes in pathways involving cell cycling and mitosis, and osteogenic differentiation, including WNT signalling, extracellular matrix (ECM) organization and matrix metalloproteinases (MMPs), in FOSΔ as compared to empty vector cells, indicating decreased proliferation and osteogenesis.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-18T17:40:26.015255+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001292","title":"Liquid biopsy to identify taxane resistance in castration-resistant prostate cancer patients","description":"Taxanes are life-prolonging treatments for patients with advanced prostate cancer. However, treatment resistance and lethal disease invariably develops. We here used liquid biopsies to identify and characterize resistance to cabazitaxel using a targeted sequencing panel (PCF-SELECT).","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-29T12:13:13.358647+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001293","title":"Single cell atlas of relapsed/refractory large B-cell lymphoma","description":"Relapsed/refractory large B-cell lymphomas (rrLBCL) are clinically and biologically diverse lymphoid malignancies with intricate microenvironments that play a key role in disease development. In this study, we used single-nucleus multiome profiling along with bulk DNA and RNA sequencing on 120 tumor and control biopsies to comprehensively characterize the various cell types and subsets found in rrLBCL tumors. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[40920660],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001294","title":"Combinatorial tumor suppressor gene targeting immortalizes primary pancreatic duct cells, resulting in temporal, deterministic structural patterns across the genome.","description":"Generation of novel, immortalized pancreatic duct epithelial cells through combinatorial CRISPR/Cas9 gene editing main driver genes. In-depth genomic signature confirmed gene editing and revealed deterministic structural changes from early to later passages. The purpose of the study is to generate long-read sequencing data to analyze structural variants in primary duct cell lines at two distinct evolutionary time points (passage 10 and 25).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001295","title":"Longitudinal analysis of bone marrow heterogeneity reveals the co-evolution of malignant B cells and their T-cell niche supporting follicular lymphoma persistence ","description":"Follicular Lymphoma (FL) is an indolent lymphoid malignancy characterized by cycles of remission and relapse, reflecting the inability of current therapies to fully eradicate tumor cells. Our hypothesis is that rare cancer precursor/persister cells (CPCs) evade treatment by homing to a protective tumor microenvironment, particularly within the bone marrow (BM), and/or by adopting  specific cellular states, and form a rare reservoir of residual cells seeding lymphoma recurrence. To adress this, we collected paired BM samples at diagnosis and one year post-therapy from a clinical trial (FLIRT trial, NCT02303119) and applied multi-modal single-cell analysis to dissect the transcriptomics determinants of rare drug-tolerant persister cells and their surrounding T-cell niche.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-09-30T10:36:49.941347+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001296","title":"Whole-exome sequencing and RNA-seq data of paired normal-tumour samples from MMR-proficient early-onset colorectal cancer patients","description":"This study aims to identify novel hereditary colorectal cancer predisposition genes by performing whole-exome sequencing and RNA-seq of paired normal colonic mucosa and colorectal cancer samples from 19 patients diagnosed with MMR-proficient colorectal cancer at an age of 50 years or younger. Both whole-exome and RNA sequencing were performed on the Illumina platform.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-07T11:43:34.833742+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001297","title":"ABHD11 inhibition drives sterol metabolism to modulate T cell effector function and alleviate autoimmunity","description":"Chronic inflammation in autoimmunity is driven by hyperactive T cells with dysregulated metabolism. ABHD11 is a mitochondrial hydrolase that supports alpha-ketoglutarate dehydrogenase function and has been associated with remission in rheumatoid arthritis. To explore its role in T cell function, we used CRISPR/Cas9 to knock down ABHD11 in Jurkat T cells and performed RNA-Seq analysis. Differential gene expression revealed widespread transcriptional changes, with sterol-related pathways among the most significantly enriched. These findings highlight ABHD11 as a potential regulator of metabolic programming in T cells with implications for autoimmunity.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-08T17:44:31.128855+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001298","title":"Phylogenetic analysis of paired breast carcinomas identifies genetic events associated with clonal recurrence and invasive progression","description":"Development of ipsilateral breast carcinoma following diagnosis of breast ductal carcinoma in situ (DCIS) has been assumed to represent recurrence of the primary tumour. However, this may not be the case and it is important to know how often recurrences are new tumours. Ipsilateral primary-recurrence pairs (n=78) were sequenced to test their clonal relatedness. Shared genetic events were identified from whole exome sequencing (n=54 pairs) using haplotype-specific copy number and phylogenetic analysis. The remaining pairs were sequenced by a targeted panel or low-coverage whole genome sequencing. We included 32 non-recurrent DCIS to compare recurrent and non-recurrent disease. We found that 7% of DCIS recurrences were non-clonal by whole exome sequencing, indicative of a new breast carcinoma. Lower resolution methods detected a higher non-clonality rate (29%). Comparing primary DCIS with their recurrences found that evolution of DCIS to invasive disease was associated with increased ploidy and copy number events. TP53 mutations were enriched in DCIS with clonal recurrence compared with non-recurrent DCIS. Our results verify that de novo “recurrent tumours” of independent origin occur in patients who may be at high risk.\r\n(https://www.biorxiv.org/content/10.1101/2024.05.19.594731v2.full)","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-10T15:46:38.165088+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001299","title":"Single-myofiber RNA sequencing reveals myofiber-level transcriptomic heterogeneity and DUX4 activation in FSHD muscle biopsies","description":"Although aberrant expression of the transcription factor DUX4 in skeletal muscle is widely regarded as the primary driver of facioscapulohumeral muscular dystrophy (FSHD), its assumed sporadic and transient nature complicates efforts to fully characterize its transcriptional impact. Moreover, the cellular heterogeneity within FSHD muscle biopsies remains only partially understood. In this study, we applied single-myofiber RNA sequencing (sfRNA-seq) to muscle biopsies from FSHD patients to address this heterogeneity.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001300","title":"In vitro modeling of renal injury-induced cardiac effects using human iPSC-derived organoids ","description":"The bidirectional communication between the heart and kidney essential for physiological homeostasis, with injury in one organ often impairing in the other. Although cardiorenal crosstalk is clinically relevant in conditions such as cardiorenal syndrome (CRS), the underlying molecular and cellular mechanisms remain poorly understood, and in vitro models are lacking. Here, we developed a co-culture system using human induced pluripotent stem cell (hiPSC)-derived kidney organoids (kOs) and cardiac microtissues (cMTs) to model the cardiorenal axis. \r\n\r\nkOs exposed to nephrotoxic compounds for 72 hours displayed glomerular and tubular damage, reduced cell viability, and altered gene expression. When subsequently co-cultured with cMTs for 72 hours, injured kOs induced secondary cardiac dysfunction characterized by reduced cell viability, impaired contractility, and endothelial cell loss. These findings demonstrate that kidney injury can elicit detrimental effects on cardiac tissues in vitro. This organoid-based platform offers a valuable tool for studying cardiorenal interactions and underlines the potential of multi-organ models for investigating mechanisms of interdependent organ dysfunction.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-20T16:27:39.477013+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001301","title":"An allele-resolved nanopore-guided tour of the human placental methylome","description":"The placenta is a temporary organ present during pregnancy that is responsible for coordinating all aspects of pregnancy between the mother and fetus. It has a distinct epigenetic, transcriptomic, and mutational landscape with low levels of methylation, high numbers of transcribed loci, and a high mutational burden relative to somatic tissues. We present this landscape through the application of nanopore sequencing technology to provide a more comprehensive picture of female placental genomics and methylomics along with integrated haplotype-resolved transcriptomic analyses across eight trios. Whole genome sequencing of trios allows robust phasing, permitting comprehensive genome-wide investigation of parent-of-origin methylation and transcription. This enhanced view facilitates identifications of many new differentially methylated regions (DMRs), both conserved and differing between individuals, as well as novel imprinted genes.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-07T08:55:50.841668+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001302","title":"ctDNA detectability and representativeness in seven body liquids from female patients with metastatic breast cancer - lpWGS","description":"low-pass Whole Genome Sequencing (lpWGS) to assess the representativeness of seven body liquids from female patients with metastatic breast cancer.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-08T17:56:16.151464+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001303","title":"ctDNA detectability and representativeness in seven body liquids from female patients with metastatic breast cancer - WES","description":"Whole Exome Sequencing (WES) to explore the mutational status of seven body liquids from female patients with metastatic breast cancer.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-08T17:56:17.690682+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001304","title":"Genomics and Transcriptomics data from primary RT samples","description":"We generated a multi-omic dataset from 20 formalin-fixed, paraffin-embedded (FFPE) lymph-node biopsies of Richter transformation (RT) collected in 2010–2020, comprising targeted DNA sequencing with Illumina TruSight Oncology 500 for all cases and bulk RNA-seq for 14/20 samples.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001305","title":"Whole genome sequencing data of pediatric hypodiploid acute lymphoblastic leukemia","description":"Hypodiploid acute lymphoblastic leukemia (ALL) is a rare subtype of B-cell ALL characterized by  chromosome number < 45 , encompassing near-haploid (24–29 chromosomes) and low-hypodiploid (30–39 chromosomes) subgroups. These subgroups display distinct genetic landscapes, including Ras and receptor tyrosine kinase pathway alterations in near-haploid ALL, and frequent IKZF2, RB1, and germline TP53 alterations in low-hypodiploid ALL. Clinically, hypodiploid ALL is associated with dismal prognosis, with 5-year overall survival rates often between 50-70% in children and markedly worse in adults. Despite advances in risk stratification and MRD-guided therapy, allogeneic stem cell transplantation remains the current standard recommendation for affected patients.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-07T08:56:50.667432+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001306","title":"T cell receptor repertoire in cell-free DNA as a proxy for tumor infiltrates in patients treated with pembrolizumab","description":"Profiling tumour and systemic T-cell receptor (TCR) repertoires can identify features associated with clinical benefit of cancer patients on immune checkpoint blockade therapy. This study reports on diversity and specificity analysis of TCR sequences from 59 tumor, 306 peripheral blood (PBMC), and 73 cell-free DNA (cfDNA) samples from 81 patients with solid tumors treated with pembrolizumab. This analysis reveals that head and neck carcinomas have significantly lower PBMC diversity and shorter persistence of pembrolizumab-induced diversification compared to other cancers. Using GLIPHII (Grouping Lymphocyte Interactions with Paratope Hotspots), we find that tumor-derived clonotypes form non-microbial specificity signatures that are shared across patients and cancer types. Tumor-derived clonotypes are enriched in cfDNA compared to PBMCs, despite the diversity of cfDNA TCR repertories being two orders of magnitude lower than PBMCs. TCRs shared between tumors and cfDNAs persist in PBMCs beyond 50 weeks of treatment, suggesting cfDNA captures clonotypes contributing to anti-tumor immune surveillance.","abstract":null,"study_type":"Resequencing","pubmed_ids":[40875293],"external_links":null,"is_released":true,"released_date":"2025-12-19T13:59:38.702753+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001307","title":"Mantle Cell Lymphoma: Atlas of Blood Cancer Genomes","description":"Despite improved approaches to prognostication in mantle cell lymphoma (MCL), the impact of specific genomic aberrations is not well-described beyond TP53, which is well recognized as a high-risk marker across malignancies and widely assessed at time of diagnosis. However, since outcomes in patients without TP53 aberrations can be highly variable and difficult to predict, additional molecular markers are needed to identify patients who are at high risk for early relapse and inferior OS (Bond et al, Blood Adv 2021). In this study, we used comprehensive whole exome and transcriptome sequencing to genomically assess the prognostic impact of recurrent abnormalities in patients with MCL with and without TP53 aberrations.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001308","title":"TONIC-Trial-cfDNA-Project","description":"Cell-free DNA (cfDNA) is an emerging technology to predict and monitor response to cancer treatment, including immune checkpoint blockade (ICB). However, data on cfDNA dynamics during ICB in metastatic triple negative breast cancer (mTNBC) are limited. While most applications of cfDNA involve assays that focus on mutation detection, mTNBC and multiple other cancer types are driven by copy number alterations (CNAs).  We evaluate cfDNA-based copy number profile abnormality (CPA) score as a potential biomarker for monitoring ICB response in mTNBC, analyzing data from 87 patients enrolled in stage 1 and stage 2 of the TONIC-trial. We find significant concordance between cfDNA-based and tissue-based CNA profiles. Additionally, responders show a decrease in CPA scores upon ICB at week 6 (3 cycles of nivolumab). These findings underscore the potential of cfDNA-based CNA dynamics as a non-invasive biomarker for ICB early response assessment in patients with mTNBC.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-07T12:47:01.943753+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001309","title":"Clinical genomics for St Jude total therapy study 17","description":"Clinical genomics for St Jude total therapy study 17","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001310","title":"Whole-Genome Shotgun Metagenomic Analysis of Rectal Mucus for Colorectal Cancer Detection","description":"This study evaluates the use of rectal mucus as a minimally invasive biospecimen for colorectal cancer (CRC) detection through whole-genome shotgun metagenomic sequencing. 408 rectal mucus samples were collected from patients suspected to have colorectal cancer and sequenced. These samples were analyzed to characterize microbial community composition and its association with CRC stage and anatomical site. These data provide insights into tumor-proximal microbiome signatures and demonstrate the potential of rectal mucus sampling for early and accurate CRC diagnosis. This is 1 of 4 sequencing experiments on the same sample type.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-16T10:31:08.61861+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001311","title":"Rare Germline Variants in CDKN2A-Negative Children and Adolescents with Cutaneous Melanoma","description":"Cutaneous melanoma is a complex disease influenced by both environmental and genetic factors. Inherited susceptibility plays a significant role, involving a combination of high-, intermediate-, and low-penetrance genes. Melanoma in children and adolescents has been speculated to have a stronger genetic component due to the early onset. This study investigates germline variants in early-onset melanoma through exome sequencing of 154 patients in Australia diagnosed with cutaneous melanoma before the age of 20.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-07T13:03:27.553011+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001312","title":"Recurrent intra-tumour heterogeneity is a hallmark of metastatic prostate cancer","description":"The evolution of cancers from low grade to metastatic disease is a major determinant of cancer mortality. Cancer evolution involves a complex interplay between cell intrinsic genetics and transcriptional alterations and the extrinsic microenvironment. To define the key mechanisms underpinning metastatic development, we focused on the most lethal form of prostate cancer, metastatic castration-resistant prostate cancer, and employed single-cell multi-omics and whole-genome sequencing to deeply profile 34 metastatic lesions from 9 patients obtained from rapid autopsy. We found that intra-tumour heterogeneity is an indicator of key evolutionary processes, characterised by recurrent tumour populations acting as critical functional components of the tumour ecosystem, irrespective of clonal and microenvironmental backgrounds. Unexpectedly, microenvironments across metastatic sites played a limited role while clonal evolution primarily promoted transcriptional noise. Intra-patient functional convergence of tumour ecosystems was observed across metastatic sites, pointing towards system-level selection pressures that drive the heterogeneity landscape of mCRPC. Our findings reveal functional evolutionary convergence of metastatic disease into units of intra-tumour heterogeneity identifying critical determinants of metastatic progression for therapeutic targeting.\r\n\r\nNote: matched WGS for some tumour single-cell experiments, as well as germline WGS for patients CA0027, CA0034, CA0035, CA0043, and CA0076, can be found in EGAS00001006598.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-24T15:08:25.321768+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001313","title":"Comprehensive benchmarking of methods for mutation calling in circulating tumor DNA","description":"This study provides a comprehensive benchmarking resource for somatic variant detection in cell-free DNA (cfDNA) from cancer patients. Longitudinal plasma samples from colorectal and breast cancer cohorts were selected to create patient-matched dilution series spanning ultra-low to high circulating-tumour-DNA (ctDNA) fractions, while preserving each individual’s germline and clonal haematopoiesis background. Deep whole-genome sequencing (150×) and ultra-deep whole-exome sequencing (2,000×) generated a reference call set of ~37,000 single-nucleotide variants and ~58,000 insertions/deletions. These data enabled systematic evaluation of nine somatic variant callers across variable ctDNA levels and sequencing depths, and were further used to explore machine-learning–guided parameter tuning. The resulting dataset offers an openly accessible framework for developers and clinicians to assess and optimize somatic variant calling in liquid biopsy applications.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-16T09:43:01.18013+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001314","title":"Enzymatic Methyl-Seq Rectal Mucus","description":"Enzymatic methyl sequencing of rectal mucus samples from patients suspected to have colorectal cancer. This is 1 of 4 sequencing experiments on the same sample type.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-20T16:21:09.081162+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001315","title":"Raw sequencing of single-cell RNA-seq data of a phase II clinical trial (NCT03419481)","description":"This is a single-arm Phase II trial of pembrolizumab in patients with hepatitis B virus-related hepatocellular carcinoma with parallel study on baseline and serial change in the immune environment.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-28T09:39:06.00471+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001316","title":"Low-input PCHi-C data in CD4+ T cells","description":"Low-input PCHi-C data in CD4+ T cells from Malysheva et al.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-24T12:14:51.880837+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001317","title":"Immune control of functional memory CD8 T cells in normal-appearing vitiligo skin ","description":"This study aimed to characterize immune cell states in nonlesional (NL) and perilesional (PL) skin of patients with vitiligo using single-cell RNA sequencing. Shared CD8⁺ T cell clusters were detected in both regions, with PL-derived cells enriched for immune activation pathways and NL skin showed stronger infiltration of regulatory T cells. These findings reveal functional T cell heterogeneity in vitiligo and highlight regulatory mechanisms that may limit depigmentation in NL skin.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-07T13:37:58.181936+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001318","title":"Integrated Single-Nucleus and Spatial Transcriptomics Elucidate Heterogeneity and Hypoxia-Driven Organization of Supratentorial Ependymoma","description":"Supratentorial ependymomas are often life-threatening brain tumours that are characterised by significant molecular heterogeneity. In this study, single-nucleus (n = 63) and spatial transcriptomics (n = 30) was performed to delineate the cellular and spatial landscape of supratentorial ependymoma. This study characterises the transcriptional consensus programs of this entity and connects them to clinical outcome. Two previously undescribed programs – associated with the remodelling of the extracellular matrix and the ZFTA fusion identity – are shown to be related to highly unfavourable outcome and to be exclusive to ZFTA fusion-positive tumours. Also, Hypoxia is proposed as the potential driver of spatial organisation, which may affect treatment success.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-13T15:36:10.718861+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001319","title":"End motifs analysis of circulating DNA from the plasma of patients with stage II-III breast cancer (n=50), stage I-III non-small cell lung cancer (n=56), metastatic colorectal cancer (mCRC) (n=15) and healthy individuals (n=37)..","description":"We have developed an algorithm designed to discriminate cancer patients and healthy individuals based on cirDNA fragment end motif analysis assisted by machine learning, using data obtained from shallow whole genome sequencing (a method we call EMA). We applied EMA to cirDNA from the plasma of patients with stage II-III breast cancer, stage I-III non-small cell lung cancer, and metastatic colorectal cancer (mCRC). CirDNA from 158 individuals was prepared following the conventional double-stranded DNA library preparation (DSP). We also performed a single-stranded DNA library preparation (SSP) using mCRC patients and healthy control cirDNA, which allowed us to make the first ever end motif analysis in the literature which compares the use of DSP and SSP. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-14T12:56:30.439308+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001320","title":"Lessons learned from the exome sequencing of nine cases of infertility and the way forward ","description":"This study investigated the role of exome sequencing in the diagnosis of male and female infertility. Nine unrelated cases referred between 2019 and 2024 were analysed using exome sequencing, with segregation confirmed by Sanger sequencing and functional assays for splicing variants. We identified nine causative variants in genes including TUBB8, PATL2, CCDC39, STAG3, KIAA0319, FBXO43, AGBL5/BBS7, PLCZ1, and HS6ST1, six of which were novel. The findings highlight diverse reproductive phenotypes such as oocyte maturation arrest, early embryonic arrest, spermatogenic failure, and syndromic infertility. This work demonstrates the value of combining genetic, functional, and clinical approaches to improve diagnostic yield and patient care in reproductive failure.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-16T09:25:12.28792+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001321","title":"RNA004 DRS METTL5 variant","description":"RNA004 is a method for direct RNA sequencing (DRS) that holds promise to enhance the detection of modopathies. To this end, we provide DRS data for a patient sample harboring heterozygous inactivating SNPs for the methyltransferase METTL5, which modifies m6A on 18S rRNA. Companion datasets are 1) EGAS50000001201 for DRS of a healthy control with intact METTL5 and 2) PRJEB74238 for IVT 18S rRNA vector data as unmodified control.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-23T13:04:17.622013+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001322","title":"ChIP-seq analysis of clear cell renal cell carcinoma","description":"In order to understand the epigenetic basis on ccRCC, we performed ChIP-seq on 3 ccRCC cell lines (786-O, A498, UMRC-2), and 1 normal kidney epithelium cell line (HK-2), cultured under normoxic (20% O2) and hypoxic (0.05% O2) conditions. This study analysed data from H3k4me1, H3K4me3, H3K27ac, H3k27me3, H3k36me3, CTCF, and HIF1A","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-05T16:34:44.381158+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001323","title":"3D chromatin analysis of clear cell renal cell carcinoma using micro-C ","description":"To investigate the 3D structure of chromatin in ccRCC, we performed micro-C on 3 ccRCC cell lines (786-O, A498, UMRC-2), and 1 normal kidney epithelium cell line (HK-2), cultured under normoxic (20% O2) and hypoxic (0.05% O2) conditions","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-05T16:34:40.898064+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001324","title":"Gene expression analysis of clear cell renal cell carcinoma","description":"To identify genes that are differentially expressed across different conditions (cancer vs normal, normoxic vs hypoxic), we performed RNA-seq in 3 ccRCC cell lines (786-O, A498, UMRC-2), and 1 normal kidney epithelium cell line (HK-2), cultured under normoxic (20% O2) and hypoxic (0.05% O2) conditions. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-05T16:34:39.236558+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001325","title":"Chromatin accessibility of clear cell renal cell carcinoma","description":"To investigate chromatin accessibility in ccRCC, we performed ATAC-seq in 3 ccRCC cell lines (786-O, A498, UMRC-2), and 1 normal kidney epithelium cell line (HK-2), cultured under normoxic (20% O2) and hypoxic (0.05% O2) conditions","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-05T16:34:42.646565+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001326","title":"SU2C GSC WGS","description":"WGS data for the SU2C project for 34 GSC (glioma stem cell line) samples. This data consists of WGS samples new to Owen Whitley's 2022 thesis, second data chapter, that were not used in Richards et al. 2021 (EGAS00001004395). The overall goal here was to perform mutation calling on cancer stem cell lines with matched bulk RNA-seq, ATAC-seq, DNA methylation, and miRNA-seq data wherever possible (see  EGAS50000000629, EGAS50000000634, EGAS50000000637, and EGAD00001006813 for more details)\r\nMatched blood samples will be provided in a separate dataset. All lines denoted as \"BT\" were cultured in sphere culture conditions by Samuel Weiss's lab, while all lines denoted as \"G\" were cultured in 2D culture conditions by Peter Dirks' lab at the hospital for Sick Children.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001327","title":"DEPArray-based sorting of pure carcinoma and stromal populations from formalin-fixed paraffin-embedded (FFPE) tissues followed by targeted sequencing","description":"To overcome the challenges of low DNA yields, degraded DNA by formalin fixation and diluted signal of genomic aberrations by non-carcinoma components in the heterogeneous FFPE samples, we isolated pure carcinoma and stromal cells using the DEPArray™ NxT system, a microchip-based digital sorter that allows isolation of pure, homogeneous subpopulations of cells from FFPE samples. We isolated pure carcinoma and stromal cell populations from 12 FFPE tissues, including tissues from 9 primary and metastatic breast cancer and 3 primary ovarian high-grade serous carcinomas. This was followed by a targeted panel for somatic mutation and sCNA analysis (7 samples), subject to cell availability. Mutation analysis was performed successfully in 6/7 samples and somatic mutations were detected in all of them. ","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-16T09:43:02.906759+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001328","title":"DEPArray-based sorting of pure carcinoma and stromal populations from formalin-fixed paraffin-embedded (FFPE) tissues followed by shallow whole genome sequencing","description":"To overcome the challenges of low DNA yields, degraded DNA by formalin fixation and diluted signal of genomic aberrations by non-carcinoma components in the heterogeneous FFPE samples, we isolated pure carcinoma and stromal cells using the DEPArray™ NxT system, a microchip-based digital sorter that allows isolation of pure, homogeneous subpopulations of cells from FFPE samples. We isolated pure carcinoma and stromal cell populations from 12 FFPE tissues, including tissues from 9 primary and metastatic breast cancer and 3 primary ovarian high-grade serous carcinomas. This was followed by downstream shallow whole genome sequencing (WGS) for copy number landscape profiling for 10 samples. Seven out of 10 samples (even some with low tumour content or of old age) produced good quality genomic data, detecting sCNA in all carcinoma population samples but not in the stromal populations. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-16T09:43:05.656697+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001329","title":"An ancient DNA perspective on the Russian Conquest of Yakutia","description":"Yakut communities from northeastern Siberia inhabit some of the coldest environments on Earth preserving an extraordinary archaeological record. Their history was profoundly reshaped by the Russian conquest, which introduced cereals, pathogens and Christianity from 1632 CE. However, the biological impact of these transformations remains unknown. Here, we generated extensive ancient DNA data to elucidate contemporary changes in Yakut genomic diversity and oral microbiomes. We found Yakut origins tracing back to local populations that admixed with trans-Baikal groups migrating as the Great Mongol Empire spread. Despite the Russian conquest, the Yakut gene pool and oral microbiomes appeared largely stable, though smallpox strains distinct from those documented in Europe by ~1650 CE circulated. Marital practices generally maintained low consanguinity, with the exception of one female bearing the latest markers of traditional shamanism, who was the daughter of second-degree relatives.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-24T15:32:51.895849+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001330","title":"Inhibition of high CXCR4 with Motixafortide and absence of single-cell MRD predict outcome after AML consolidation.","description":"Understand how single-cell sequencing enables precise MRD tracking and reveals clonal heterogeneity in AML.\r\nLearn how CXCR4 expression serves as a biomarker for predicting relapse risk and therapeutic response.\r\nRecognize the clinical utility of biomarker-driven CXCR4 inhibition, and its role in advancing personalized AML consolidation strategies.\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001331","title":"Alterations of whole genome and extrachromosomal circular cell-free DNA fragmentomes across the cancer care continuum","description":"The origins and properties of cancer-associated genetic changes in cell-free DNA (cfDNA) are not fully understood. Through genome-wide analyses of 1,807 samples from 1,064 patients across eight common cancer types, we identified extrachromosomal circular DNA (eccDNA) as a source of cfDNA fragments.  Characterization of eccDNA-derived cfDNA fragments along with single base substitutions, small insertions and deletions, rearrangements, and phased variants in single cfDNA molecules, revealed differences between tumor tissues and cfDNA, with an increase in tumor-derived cfDNA alterations at epigenetically repressed regions and a decrease at active promoters.  Combination of variant characteristics with individual error rates and machine learning analyses enabled tumor-informed and tumor-independent measures of circulating tumor DNA for early detection, detection of minimal residual disease, and for monitoring patients during therapy.  The universal nature of eccDNA and other tumor-derived characteristics of cfDNA may be broadly useful for cancer detection.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-06T08:45:44.222032+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001332","title":"Acute Promyelocytic Leukemia: Atlas of Blood Cancer Genomes","description":"Acute promyelocytic leukemia (APL) is a common type of acute myeloid leukemia with unique clinical characteristics and an excellent prognosis with current all-trans retinoic acid and arsenic trioxide (ATRA + ATO) therapy. However, some patients still experience poor outcomes. In this study, we sought to better understand genomic features that correlate with poor clinical outcomes. We accrued 126 patient samples. Our comprehensive genomic and transcriptomic profiling of 126 patients identified a diverse set of genetic events including FLT3, WT1, and ATM. We found that mutations in WT1 have a significant impact on progression-free survival (p<0.005). We also evaluated the expression of markers associated with myeloid differentiation, particularly the combined effects of the protease neutrophil elastase (ELANE) and myeloperoxidase (MPO) revealing significant overall survival (OS) differences (p=0.03). These findings demonstrate that even in the era of ATRA + ATO therapy, APL patients may be risk-stratified by mutation and gene expression profiling. Our data support the inclusion of WT1 in clinical NGS to examine its role in affecting outcomes in these patients.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001333","title":"Broad utility of ultrasensitive analysis of ctDNA dynamics across solid tumors treated with immunotherapy","description":"Prior studies have suggested the biomarker potential of plasma circulating tumor DNA (ctDNA) in cancer patients treated with immune checkpoint inhibitors (ICIs). In order to characterize the potential role of ultrasensitive ctDNA detection in the management of these patients we have performed tumor whole-genome-informed, ultrasensitive ctDNA analysis—tracking approximately 1,800 tumor-specific mutations per patient—in a retrospective cohort (n=136) and a prospective validation cohort (n=66) across 24 cancer types treated with ICIs alone or in combination with bispecific antibodies or immune cell engagers. Analyzing 1,455 longitudinal samples, we found that ctDNA molecular response measured as early as 3 weeks after treatment initiation correlated with improved progression-free and overall survival, while ctDNA clearance at any time strongly correlated with radiological response and prolonged survival. Additionally, ctDNA dynamics distinguished true progression from pseudoprogression and predicted outcomes in patients receiving continued immunotherapy beyond initial progression. This study highlights the broader applicability of ultrasensitive ctDNA as a biomarker across cancer types and immunotherapy modalities.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-22T14:40:02.488513+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001334","title":"EXPRESSION OF ANTIBODY-DRUG CONJUGATE TARGETS IN BREAST CANCER METASTASES AND NORMAL TISSUE","description":"Using bulk mRNA sequencing, we investigated the expression of 72 ADC targets, which are clinically approved or under investigation, in 909 samples (64 primary untreated, 749 metastatic, 96 normal) from 30 female patients from our post-mortem tissue donation program UPTIDER (NCT04531696). The study explores changes in target expression across multiple samples to identify novel targets of clinical interest and validation","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-21T14:33:19.408935+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001335","title":"Angioimmunoblastic T-cell Lymphoma: Atlas of Blood Cancer Genomes","description":"AITL is a clinically aggressive lymphoma with poor prognosis and few effective targeted therapies. While much is known about the effects of recurring mutations in epigenetic regulators and T cell receptor genes, the contribution of the EGFJAK/ STAT signaling pathway to AITL pathogenesis remains unclear. Whole exome and targeted deep sequencing were performed on biopsy samples from two AITL cohorts (n=251) as part of the Atlas of Blood Cancer Genomes Project. Pathway enrichment, clonal analysis, molecular dynamic modeling, and in vitro assays were used to evaluate the impact of EGF-JAK/STAT mutations, particularly EGFR variants. EGF-JAK/STAT mutations were identified in 19.5% of cases, correlating with worse progression-free and overall survival. EGFR mutations—most notably R803W and A864V— localized to dominant tumor clones and promoted activation of STAT3/5 and ERK pathways. These effects were mitigated by EGFR inhibitors in cell models, suggesting that these drugs could be effective treatments for patients harboring these mutations. In conclusion, EGF-JAK/STAT pathway alterations define a subset of AITL with poor prognosis. EGFR mutations represent potentially actionable targets, supporting further exploration of EGFR-directed therapies in this malignancy. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001336","title":"NOUS-209 off-the-shelf immunotherapy has the potential to hit primary and metachronous colorectal and urothelial cancer in Lynch syndrome","description":"Lynch syndrome is an inherited cancer predisposition characterized by the development of microsatellite-instable tumors, most commonly colorectal and urothelial cancers. These cancers harbor recurrent frameshift mutations (FSMs) that generate shared neoantigens, creating opportunities for targeted immunotherapy. NOUS-209 is a viral-vector–based cancer vaccine encoding 209 of these shared neoantigen peptides. This study investigated the presence and evolution of NOUS-209 target FSMs in Lynch syndrome–associated tumors, revealing their persistence across primary and metachronous cancers and supporting the rationale for NOUS-209 as a preventive immunotherapy.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-06T12:34:07.444616+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001337","title":"Longitudinal ctDNA profiling in metastatic colorectal cancer, whole exome sequencing.","description":"This study contains low-pass whole genome sequencing data for 141 ctDNA samples collected over three timepoints (baseline, best response and progression disease) from 47 patients with metastatic colorectal cancer.  In addition, high-depth whole exome sequencing was performed on 111 samples from 37 patients. Matched genomic DNA (n=37) from peripheral blood was also profiled through standard whole exome sequencing.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001338","title":"Longitudinal ctDNA profiling in metastatic colorectal cancer, low pass whole genome sequencing.","description":"This study contains low-pass whole genome sequencing data for 141 ctDNA samples collected over three timepoints (baseline, best response and progression disease) from 47 patients with metastatic colorectal cancer.  We aimed to analyse copy number profiles, to determine purity and ploidy. We also investigated the pattern of DNA fragment density with a view to understanding transcription factor activity.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001339","title":" Investigating the differences in iPSC-derived intestinal epithelial cell behaviour and composition grown as organoid, in Transwell or Intestine-Chip.","description":"aim: Investigating the differences in iPSC-derived intestinal epithelial cell behaviour and composition grown as organoid, in Transwell or Intestine-Chip.\r\n\r\nRNA sequencing data of 21 samples of iPSC-derived intestinal epithelial cells on different model systems. \r\n3 iPSC lines Geni002, Geni007 and Geni012 differentiated into Epcam+ intestinal epithelial cells and grown on the following systems:\r\n\t6 samples: organoids exposed to EM (3) and DM+D+PD (3)\r\n\t9 samples: Transwell exposed to EM/EM (3), DM+D+PD/DM+D+PD (3), EM/DM+D+PD (gradient, 3)\r\n\t6 samples: Emulate Chip exposed to EM/EM (3) and EM/DM+D+PD (3)\r\n\r\nEM: expansion medium\r\nDM+D+PD: differentiation medium including DAPT and PD0325901\r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-27T12:15:34.672737+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001340","title":"CLUSTER RNAseq Analysis of Juvenile Idiopathic Arthritis patients in anti-TNF cohort","description":"The study aims to analyse anti-TNF response in JIA patients of UK cohort based on gene expression using RNAseq. The blood samples were collected prior to patients receiving anti-TNF for PBMC isolation followed by sorted cells into 4 different immune cell types.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001341","title":"NAR-GAB  2025 deposit data","description":"Human exome FASTQ (paired-end, gz): rare-disease cohort for the NAR-GAB 2025 study on splicing-SNV prioritization.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001342","title":"Dynamic human admixture histories over the past ~1,300 years at the northern Himalayan frontier","description":"Archaeological and paleogenomic evidence from the Tibetan Plateau and high-altitude Central Himalayas suggest biocultural connections with each other and with lowland East, Central, and South Asia. However, genetic histories at the northern frontier of the Indian Himalayas, which is geographically more proximal to Central and lowland South Asia, remain underexplored. We analyzed genome-wide data from 7 ancient (~2300 to 100 years old) and 10 present-day individuals from the northern Indian Himalayas and one ~3370-year-old individual from the Central Himalayas in Nepal. Ancient and present-day individuals from the northern Himalayas predominantly have Tibetan-related genetic ancestry, likely the source of high-altitude adaptive variants in these individuals, with substantial Steppe-related genetic ancestry that is observed in all individuals dating between ~1300 years and present day. In addition, some present-day individuals have lowland South Asian admixture. Our analyses reveal a dynamic interplay between genetic admixture and continuity in the northern Himalayas.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-24T16:02:19.243322+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001343","title":"Proteomic Characterization of Intrahepatic Cholangiocarcinoma Identifies Risk-Stratifying Subgroups, Proteins Associated with Time-To-Recurrence, and mTOR Effector Molecule EIF4A1 as a Druggable Therapeutic Target","description":"Using mass spectrometry-based proteomics, we analyzed two independent cohorts comprising 80 and 62 treatment-naive ICC tumors, 67 adjacent non-malignant tissues, and 9 patient-derived xenografts (PDX).\r\nIn the first cohort, we identifed two subclusters with distinct times-to-recurrence (TTR). A 4-protein classifier trained on our data cohort accurately stratifies these ICC clusters in the Dong et al. dataset (2022) and in our independent second cohort, revealing similar associations between proteomic motifs and clinical outcomes.\r\nThe Translation regulator EIF4A1 emerges as a therapeutic target, as its inhibition with novel drug eFT226 significantly reduces tumor growth in an ICC PDX model.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-26T17:49:54.092197+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001344","title":"Transcriptomic analyses of patient haematopoietic stem and progenitor cells from TET2- mutated myelodysplastic syndromes","description":"TET2 is one of the most commonly mutated genes in myeloid malignancies. In this study we aimed to examine transcriptional profile of haematopoietic stem and progenitor cells (HSPC) isolated from patients diagnosed with myelodysplastic syndrome (MDS) with TET2 mutations. We profiled HSPC-enriched fraction (CD34+), short-term reconstituting cell (STRC, CD34+CD38+) fraction and HSC fraction (CD34+CD38-). ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001345","title":"Nodular Lymphocyte-Predominant Hodgkin Lymphoma: Atlas of Blood Cancer Genomes","description":"Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare cancer characterized by an indolent course; yet, some patients experience recurrence or transformation to aggressive T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL). We analyzed 178 NLPHL and 22 THRLBCL cases using whole transcriptome RNA sequencing to elucidate clinical, histological, and molecular characteristics. NLPHL patients were younger with favorable outcomes, whereas THRLBCL patients presented at an older age with advanced-stage disease and worse prognosis. Variant immuno-architectural patterns (IAPs) in NLPHL exhibited transcriptional profiles that overlapped with THRLBCL, especially in cases with splenic involvement and high Lymphocyte-Predominant International Prognostic Scores (LPIPS). Tumor microenvironment (TME) deconvolution revealed that classical NLPHL is rich in B cells, variant NLPHL exhibits intermediate profiles, and THRLBCL is characterized by increased infiltration of activated CD4+ and CD8+ T cells and macrophages. Notably, high LP-IPS combined with elevated follicular T-helper cell abundance was associated with worse clinical outcomes in NLPHL patients. Strong B-cell and helper T-cell signatures characterized NLPHLs, while THRLBCL was enriched for macrophage, monocyte-mediated, and cytotoxic T-cell pathways. Additionally, THRLBCLs exhibited elevated expression of immune checkpoint-related genes, suggesting an immunosuppressive TME. Top-scoring pair analysis validated a progressive transcriptional continuum from classical NLPHL to variant NLPHL, culminating in THRLBCL. These findings underscore the significance of TME composition and immune checkpoint gene expression in the pathobiology and clinical course of NLPHL and THRLBCL, offering potential avenues for targeted immunotherapeutic strategies.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001346","title":"Blastic Plasmacytoid Dendritic Cell Neoplasm: Atlas of Blood Cancer Genomes","description":"Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematologic malignancy with relatively limited molecular characterization. To address this gap, we performed integrated DNA and RNA sequencing on 88 BPDCN patients representing the largest and most ancestrally diverse cohort described to date (~77% European, ~16% Asian, ~7% African). Median age was 62.5 years with a male predominance (56%) and poor survival (median overall survival 1.4 years, median progression-free survival 1.3 years). Somatic profiling revealed recurrent mutations in epigenetic regulators (TET2, ASXL1, KMT2D), transcription factors (IKZF1, ETV6) and JAK/STAT and RAS/MAPK pathway genes. A combined model comprising ASXL1, TET2, and APC mutational status effectively stratified patients into risk groups (p < 0.001). Females had better survival compared to males (p = 0.017) reflecting an enrichment of TET2 and ASXL mutations in male patients, while female patients harbored more RAS/MAPK alterations. The role of expression in BPDCN is largely unknown. We found that CD56-negative tumors had more favorable clinical outcomes and exhibited unique immune-stromal gene signatures, suggesting a distinct biological subtype. These insights refine BPDCN risk stratification and suggest sex-specific and CD56-related biological subtypes for future therapeutic targeting.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001347","title":"MYC Inhibition By Omomyc Causes DNA Damage And Overcomes PARPi Resistance In Breast Cancer.","description":"This study investigates the role of MYC dysregulation in DNA damage response (DDR) and PARP inhibitor (PARPi) resistance in breast cancer. Using Omomyc, a direct MYC inhibitor, we demonstrate that MYC inhibition shuts down DDR genes in triple-negative breast cancer (TNBC), causing DNA repair defects and inducing DNA damage that synergizes with PARPi treatment. Through patient-derived models and clinical samples from metastatic HR-altered breast cancer patients treated with PARPi, we identify MYC transcriptional activity as a predictive biomarker of PARPi resistance. Digital spatial profiling (DSP) analysis of pre-treatment tumor biopsies reveals that patients with progressive disease have significantly elevated MYC signatures compared to responders. These findings support the therapeutic strategy of combining MYC inhibition with PARPi in PARPi-resistant breast cancers where high MYC activity predicts poor response to therapy.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-22T15:29:16.617102+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001348","title":"Human colorectal cancer single-cell RNA sequencing","description":"The aim was to investigate changes in transcriptomics following irradiation. This was studied in colorectal cancer-patient derived organoids. Analysis was performed with scRNA-seq.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[39841093],"external_links":null,"is_released":true,"released_date":"2025-10-22T06:54:31.636877+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001349","title":"Immune activation in the tumor microenvironment of renal cell carcinoma","description":"Study describes immunological responses to immunotherapy (anti-PD-1, pembrolizumab) and targeted therapy (VEGFR inhibition, axitinib) as well as anti-CD3/CD28/CD2 (Immunocult) in a patient-derived ex vivo tumor model of renal cell carcinoma. Patient-derived ex vivo tumor models were established and their treatment response studied using material from eight renal cell carcinoma patients. Samples were collected under informed consent in HUS Helsinki University Hospital, Finland. The study aims to understand immunological treatment responses in the patient tumor microenvironment.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-23T11:21:37.477889+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001350","title":"Integrated Methylation and Copy Number Analysis for Non-invasive Bladder Cancer Detection in Urine","description":"The molecular analysis of urine cell-free DNA (cfDNA) offers a non-invasive tool to advance bladder cancer (BC) management. Assessment of somatic copy number aberrations (SCNA) and DNA methylation, as singular or complementary analysis, have emerged as promising approaches for BC detection. Here, we developed an integrated analysis to assess both SCNA and targeted methylation changes from the same template molecules, named the iSECURE (integrated SEquencing-based Copy number and methylation analysis in URinE) method.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-03T15:01:37.038894+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001351","title":"Genomic evolution of pancreatic cancer at single-cell resolution","description":"This project assesses genomic evolution of pancreatic cancer using the Mission Bio Tapestri platform and Whole Exome Sequencing. The Mission Bio Tapestri platform is a single-cell DNA sequencing platform using a targeted gene panel to assess SNV/CNV. Several samples, including primary and metastatic tissue, were used to investigate changes at single-cell resolution.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-05T16:10:07.391295+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001352","title":"Anaplastic Large Cell Lymphoma: Atlas of Blood Cancer Genomes","description":"Anaplastic large cell lymphoma (ALCL) comprises biologically distinct entities based on ALK translocation status. We profiled clinical features and tumor genomics of 118 ALCL biopsy samples (n=54 ALK+, n=64 ALK-negative) to identify factors that influence survival outcomes. ALK‑negative patients showed inferior overall survival (OS) compared to ALK+ patients (p<0.05). ALK‑negative ALCL that harbored TP53 mutations had the poorest OS compared to ALK+ or TP53‑wild type, ALK-negative patients (p<0.05). Mutational burden and copy number variation (CNV) burden were highest in ALK‑negative, TP53-mutated cases compared with either of the other groups (p<0.05). Pathway analysis showed enrichment of genes involved in epigenetic regulation, DNA‑damage repair, and immune/JAK‑STAT signaling in ALK‑negative tumors. On the other hand, NOTCH pathway genes were more frequently mutated in ALK+ cases. Lollipop plots confirmed canonical STAT3 SH2 hotspot variants (Y640F) and dispersed JAK1 kinase domain mutations. This study implicates TP53 loss as a key determinant of genomic instability and clinical behavior in ALK-negative ALCL. Stratification by both ALK translocation and TP53 mutational status may refine risk assessment in this disease","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001353","title":"ALK+ DLBCL and Plasmablastic Lymphoma: Atlas of Blood Cancer Genomes","description":"We performed integrated transcriptomic and mutational profiling of 86 patient samples (PBL n=56, ALK+ LBCL n=19), revealing a shared plasmablastic phenotype that is intermediate between DLBCL and plasma cell myeloma. Recurrent STAT3 gain-of-function mutations were identified in PBL but not ALK+ LBCL. To better understand the underlying biology of these tumors, we created novel in vivo patient-derived xenograft (PDX) and PDX-derived primary culture (XDC) models of ALK-LBCL and PBL. Using these models, we showed that ALK+ LBCL is dependent on ALK fusion–mediated STAT3 signaling. ALK inhibition suppressed STAT3/MYC programs (data partially shown), and STAT3 deletion, both by CRISPR/Cas9 knock-out and degradation by STAT3 degraders, abolished viability. Conversely, STAT3 degraders were ineffective in PBL, despite STAT3-activating mutations, indicating these tumors do not rely on STAT3 activation for their survival. By demonstrating transcriptomic similarity to myeloma, we further identified high expression of plasma cell–associated targets (BCMA, CD38, SLAMF7) in PBL. Elotuzumab (SLAMF7) and daratumumab (CD38) elicited potent antibody-dependent cytotoxicity in PBL, and anti-BCMA CAR-T was also highly effective in PBL. These data establish PBL and ALK+ LBCL as distinct plasmablastic malignancies and uncover novel actionable vulnerabilities for each. Our findings support a shift away from DLBCL-based paradigms toward precision therapeutics tailored to the unique biology of these tumors.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001354","title":"Correction of the cytosine deamination artifacts in FFPE-based sequencing experiments","description":"Formalin-fixed paraffin-embedded (FFPE) samples are widely used in research and diagnostics, but cytosine deamination during fixation introduces sequencing artifacts, particularly C>T substitutions, which complicate reliable mutation detection. In this study, we systematically evaluated five computational methods and an enzymatic repair approach for FFPE artifact removal, as well as their combined application, using a custom dataset based on whole exome sequencing. Our results demonstrate that while computational strategies improve data quality, the enzymatic approach provides the most effective artifact correction. The study provides guidelines for both computational and enzymatic artifact correction strategies for reliable downstream analyses.\r\n\r\nThis project was funded by the Polish National Science Centre, grant no. 2021/41/B/NZ2/04134.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-31T14:32:11.023036+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001355","title":"Classical Hodgkin Lymphoma: Atlas of Blood Cancer Genomes","description":"cHL encompasses distinct histologic subtypes within an immune-rich tumor microenvironment, yet their biological differences remain incompletely understood. Here, we integrated clinical features, gene expression profiles and immune deconvolution with survival to identify determinants of outcome in 117 patients. Interestingly, we found that each cHL type had characteristic patterns: lymphocyte-rich cHL was enriched for B-cell and antigen-presenting cell programs with higher memory B-cell fractions, nodular sclerosis demonstrated a higher proportion of activated dendritic cells, lymphocytedepleted cases were relatively immune-depleted with increased M2 macrophages, and mixed cellularity showed intermediate features. Notably, although cHL subtypes did not differ significantly in overall survival (OS), classification of patients based on the combination of EBV status and age did significantly stratify OS, with EBV+ patients ≥60 years old showing the poorest survival (p<0.05). IDO1 was found to be upregulated in EBV+ tumors and significantly correlated with CD274 expression, suggesting the potential efficacy of a targeted immunotherapy strategy in these patients. The results of this study paint a comprehensive portrait of cHL subtypes and support evaluation of IDO1 inhibitors and other checkpoint blockade strategies specifically in EBV+ cHL patients.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001356","title":"Ouro-seq: Improved Recovery of Full-Length circRNAs from Samples with Limited RNA Content Using Short-Amplicon Suppression","description":"Circular RNAs (circRNAs) represent an emerging class of RNAs with potential roles in disease pathogenesis and promising biomarker applications. However, their detection in samples with limited RNA content, such as liquid biopsies, remains challenging due to extremely low abundance. Here, we introduce Ouro-seq, a novel long-read sequencing protocol optimized for full-length circRNA recovery. We applied Ouro-seq to urine and self-sampled cervical swab (CVS) samples from cervical cancer patients and plasma from lung cancer patients and healthy controls. Our approach significantly outperformed conventional methods, recovering 2-5 times more and substantially longer circRNA molecules. Unexpectedly, while plasma samples predominantly contained exonic circRNAs, urine and CVS were dominated by previously under characterized intergenic circRNA. We identified extensive alternative circularization and splicing events. Functional annotation revealed distinct specialization patterns among circRNA subtypes, with exonic circRNAs exhibiting enhanced miRNA sponging potential and circRNAs from unplaced genomic scaffolds showing greater peptide-coding capacity. This study significantly advances our understanding of circRNA biology in liquid biopsies and establishes Ouro-seq as a valuable tool for comprehensive circRNA characterization with potential applications in biomarker discovery and disease monitoring.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-10T17:02:01.821091+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001357","title":"PARADIGM: Combined ctDNA and serum PSA for dynamic monitoring of metastatic prostate cancer starting first-line treatment","description":"The prognosis of newly-diagnosed metastatic prostate cancer is highly variable. The PARADIGM prospective cohort study evaluated predictors of survival in blood collected at the start of each of the first six treatment cycles from 114 high-volume metastatic patients starting androgen deprivation therapy combined with docetaxel or an androgen receptor pathway inhibitor.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-30T16:44:14.770438+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001358","title":"Longitudinal single-cell transcriptomic analysis of a human iPSC model of sporadic Parkinson's disease","description":"This longitudinal study investigates the temporal dynamics of sporadic Parkinson's disease (sPD) by aiming to dissect early molecular triggers versus later progressive changes. It utilizes a human iPSC-derived neural progenitor cell (hNPC) model and compares two critical time points using scRNA-seq: an early, asymptomatic \"short-term\" (passage 20) stage and a previously published \"long-term\" symptomatic stage (GEO: GSE176160). This approach provides a high-resolution resource to understand the intrinsic, progressive nature of sPD.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001359","title":"Single-cell genomics highlight MYC-upregulation, metabolic activation, and altered cell interactions in T-PLL progression","description":"Using single-cell RNA sequencing of 28 samples from 17 treatment-naïve T-PLL patients, including 11 longitudinally acquired indolent/active pairs, we investigated molecular changes underlying disease progression. Longitudinal whole-genome sequencing (WGS) data from three patients complemented these analyses to capture genomic alterations during progression. In-silico and ex-vivo analyses identified both patient-specific lesions and shared gene expression changes characterizing active-stage T-PLL.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001360","title":"Circulating Immune cells in IMIDs from DoCTIS Project","description":"PBMCs from 184 patients with six immune-mediated inflammatory diseases (IMIDs)—rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PS), ulcerative colitis (UC), Crohn’s disease (CD), and systemic lupus erythematosus (SLE)— were profiled in the European Project DoCTIS using single-cell RNA sequencing (scRNA-seq). Multiplexed libraries were generated by pooling samples from eight donors per library.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-27T10:27:35.650309+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001361","title":"Germline variants in patients with five cutaneous melanoma","description":"Skin melanoma arises from a complex interplay between UV radiation exposure and inherited genetic susceptibility. A subset of invidiuals experience multiple independent tumours, suggestingh a stronger underlying genetic component. In this study, we investigate the germline contribution to melanoma development in individuals diagnosed with five or more primary melanomas.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-03T10:29:43.998494+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001362","title":"NeoLetExe clinical trial single-cell RNA-seq, scTCR-seq, scBCR-seq and cis-regulatory elements mapping","description":"We performed single cell RNA sequencing, single cell T cell receptor and B cell receptor sequencing on breast tumor biopsies collected from patient of the NeoLetExe clinical trial at 3 time points of neoadjuvant therapy with aromatase inhibitors.\r\nThe NeoLetExe study is a randomized open-label clinical trial aimed at evaluating the effects of sequential aromatase inhibition in postmenopausal women with ER-positive, HER-2 negative locally advanced breast cancer (stages T3-T4 and/or N2-3, including larger T2 tumors).\r\nFresh tumor biopsies were dissociated at the single cell level which when then processed using the 10x Genomics Chromium platform, using the Single-Cell 5′ RNA-seq method along with single cell BCR and TCR-seq. The target was 7,500 to 10,000 cells per well, with libraries prepared using Gel Bead, Multiplex, and Chip Kits, following the manufacturer’s guidelines. Sequencing was performed on NovaSeq6000.\r\nWe used SCAFE v1.0.065 to identify TSSs and map transcriptionally active regulatory elements.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-21T12:41:48.266502+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001363","title":"Extranodal Marginal Zone Lymphoma: Atlas of Blood Cancer Genomes","description":"Extranodal marginal zone lymphoma (EMZL) is the most common form of marginal zone lymphoma, yet its genomic and transcriptomic landscape remains incompletely understood due to the disease’s rarity and anatomical heterogeneity. Here, we present the largest comprehensive study of EMZL to date, profiling 175 patients across 20 institutions using DNA sequencing with whole-exome sequencing and targeted DNA panels and RNA sequencing. We identified a number of recurrent driver genes, with IGLL5 as the most frequently mutated gene (25% of cases) alongside recurrent alterations in known EMZL drivers such as TNFAIP3, TBL1XR1, and SPEN as well as novel drivers such as ZEB2 and LRP1B. Copy number analysis revealed recurrent trisomy of chromosomes 3 and 18 and other focal gains and losses. Transcriptomic clustering demonstrated distinct site-specific expression patterns, with gastric and ocular adnexa EMZL forming homogeneous clusters enriched for B-cell receptor signaling and NF-κB pathways. Immune deconvolution highlighted microenvironmental variation, including site-specific abundance of resting mast cells, M1 macrophages, and regulatory T cells. These findings underscore both the biological similarity and strong genetic and clinical divergence of EMZL across anatomical sites. We anticipate that this large well-annotated EMZL cohort will provide a valuable clinical, genomic and transcriptomic resource to inform future diagnostic and therapeutic strategies.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001364","title":"Primary Large B-cell Lymphoma of the CNS: Atlas of Blood Cancer Genomes","description":"CNS-LBCL is a rare aggressive lymphoma with diverse molecular and clinical characteristics and variable therapeutic responses. The lymphoma cells are confined to the CNS with no systemic involvement. Although there is increasing attention to the role of tumor microenvironment (TME), there is limited understanding of how unique CNS environments shape the biology, molecular diversity and clinical characteristics of CNS-LBCL. We studied 118 patients from multiple institutions, integrating clinical, genomic and transcriptomic data. We identified genomic alterations with distribution frequency consistent with other published studies. We found that microglia sensome and vasculature-related gene expression patterns (MSV) are associated with higher macrophage presence in the tumor microenvironment. Additionally, the MSV-high group had a lower prevalence of PIM1 and CD79B mutations and showed prolonged overall and progression-free survival compared to the MSV-low group. The results of our study indicate that MSV-linked immunoinflammatory TME plays a unique role in the biology of CNS-LBCL and may be linked to therapy responses and clinical outcomes.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001365","title":"Methylation sequencing of CSF-derived cell free DNA","description":"We sequenced and enzymatically converted cell free DNA from 268 samples from 157 patients with brain tumors and 58 control CSF patients.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-30T17:37:34.241672+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001366","title":"Adult B-precursor acute lymphoblastic leukemia RoCK and ROI single-cell transcriptome","description":"Whohle Transcriptome sequencing was performed following the manufactures protocol from BD Rhapsody. Capture of BCR::ABL1 was performed using RoCK and ROI. RoCK and ROI is based on barcoded beads of the BD Rhapsody platform. For RoCKseq specific capture, TSO oligos on BD Rhapsody beads are modified with a/ multiple capture sequence(s) specific to transcripts of interest. ROIseq, on the other hand, is based on specific primers which are spiked in during library generation, directing reads to regions of interest (ROIs). Multiple scRNAseq experiments were performed on several biological samples to validate RoCK and ROI.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-23T17:13:51.075907+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001367","title":"Frequent Genetic Alterations in Myositis Autoantigen Genes in Cancer-Associated Dermatomyositis","description":"One-third of patients diagnosed with dermatomyositis harbor an occult cancer, a rare condition named cancer-associated dermatomyositis (CAD). Emerging evidence suggests that genetic alterations in autoantibody-related genes give rise neoantigens and specific autoantibodies that initiate an autoimmune response characteristic of CAD. This study evaluated the prevalence of such genetic alterations and elucidated molecular mechanisms that may underlie their role in triggering autoimmunity. We detected highly frequent genetic alterations in autoantibody-related genes, supporting their role in the CAD pathogenic mechanisms. Distinct TCR repertoire and immune signatures between tumoral and non-tumoral tissues may underlie divergent cancer and dermatomyositis outcomes. Neglected, immunotherapy may offer clinical benefit in selected cases of CAD and warrants further investigation.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001368","title":"Somatic rearrangements causing oncogenic ectodomain deletions of FGFR1 in squamous cell lung cancer ","description":"The discovery of frequent 8p11-p12 amplifications in squamous cell lung cancer (SQLC) has fueled hopes that FGFR1, located inside this amplicon, might be a therapeutic target. In a clinical trial, only 11% of patients with 8p11 amplification (detected by FISH) responded to FGFR kinase inhibitor treatment. To understand the mechanism of FGFR1 dependency, we performed deep genomic characterization of 52 SQLCs with 8p11-p12 amplification, including 10 tumors obtained from patients who had been treated with FGFR inhibitors. We discovered somatically altered variants of FGFR1 with deletion of exons 1-8 that resulted from intragenic tail-to-tail rearrangements. These ectodomain-deficient FGFR1 variants (ΔEC-FGFR1) were expressed in the affected tumors and were tumorigenic in both in vitro and in vivo models of lung cancer. Mechanistically, breakage-fusion-bridges were the source of 8p11-p12 amplification, resulting from frequent head-to-head and tail-to-tail rearrangements. Generally, tail-to-tail rearrangements within or in close proximity upstream of FGFR1 were associated with FGFR1 dependency. Thus, the genomic events shaping the architecture of the 8p11-p12 amplicon provide a mechanistic explanation for the emergence of FGFR1-driven SQLC. Specifically, we believe that FGFR1 ectodomain-deficient and FGFR1-centered amplifications caused by tail-to-tail rearrangements are a novel somatic genomic event that might be predictive of therapeutically relevant FGFR1 dependency. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-17T10:14:05.148161+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001369","title":"Single cell RNAseq data of human neurons, Bouwen et al Nat Comm 2025","description":"Brain tumor patients often suffer from epilepsy, but the underlying neuronal changes leading to this neurological symptom are not well understood. This study examined the transcriptomic profiles of human cortical neurons collected from brain tumor patients with or without seizures. The goals of the study were to identify the molecular identities of the recorded neurons and confirm that they are layer 2/3 pyramidal neurons rather than neuron-like tumor cells; and to compare the differential gene expression profiles between patients with and without epilepsy.\r\n\r\nFor each patient, cortical neurons were rapidly isolated from surgically resected tissue and prepared using the Smart-seq2 protocol. Samples from 12 patients were sequenced on an Illumina HiSeq 2500 platform to generate their transcriptomic profiles.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-30T14:28:46.189344+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001370","title":"Using RNA-sequencing to characterize the resistance to lirafugratinib","description":"In addition to Exome-sequencing, we used RNA-sequencing to also characterize resistance to lirafugratinib with whole exome sequencing in patients with FGFR2-driven cancers, treated in the phase 1/2 ReFocus trial (NCT04526106) and enrolled in the UNLOCK program at Gustave Roussy","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-30T11:06:33.27184+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001371","title":"Using Exome-sequencing to characterize the resistance to lirafugratinib","description":"We characterized resistance to lirafugratinib with whole exome sequencing in patients with FGFR2-driven cancers, treated in the phase 1/2 ReFocus trial (NCT04526106) and enrolled in the UNLOCK program at Gustave Roussy","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-30T11:06:33.27184+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001372","title":"CD30-Positive Lymphoproliferative Disorders: Atlas of Blood Cancer Genomes","description":"Cutaneous CD30 positive lymphoproliferative disorders (CD30+ LPD) represent a biologically diverse group of diseases with highly variable clinical outcomes. We integrated clinical, genomic, and transcriptomic data from 91 patients across multiple institutions. Patients were stratified into two clinical risk groups based on treatment recommendations, confirming significantly worse overall survival among those requiring aggressive therapy (clinical code 1). Mutational profiling identified recurrent alterations in KDR, TET2, NCOR2, and PRDM1, implicating angiogenesis and epigenetic dysregulation in disease pathogenesis. Notably, KDR p.Q472H, previously linked to microvessel density and disease aggressiveness in solid tumors, was detected as a hotspot and trended toward higher frequency in lower-risk patients. Transcriptomic analysis revealed that high-risk patients exhibited upregulation of MYC targets, G2M checkpoint genes, and DNA repair pathways, indicating increased proliferative and oncogenic signaling in this group. Immune deconvolution further revealed an immunocompetent tumor microenvironment in favorable-outcome patients (clinical code 0) marked by higher abundance of resting dendritic cells (p<0.005). These findings highlight the heterogeneity of cutaneous CD30⁺ LPD and demonstrate that transcriptional programs and immune context may more accurately distinguish indolent from aggressive disease than mutational burden alone.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001373","title":"Extranodal NK/T Cell Lymphoma: Atlas of Blood Cancer Genomes","description":"Extranodal NK/T cell lymphoma (ENKTCL) is an aggressive malignancy driven by Epstein-Barr virus (EBV) infection. ENKTCL has a strong predilection for Asian populations and native populations of Central and South America. Notably, little is known of the genetic variation between populations or the prognostic significance of racial, geographic and genetic factors. To explore these factors, we performed whole exome and transcriptome sequencing on 63 tumor biopsy samples from ENKTCL patients from 17 institutions globally, with accompanying clinical data. We generated complete genomic profiles including genetic variants, copy number variants, gene expression profiles, genetic ancestry and EBV gene expression. European ancestry correlated with better overall survival in our cohort (OS, p<0.05). The most frequent driver mutations observed occurred in epigenetic modifiers such as KMT2D, TET2 and BCOR. Asian ancestry correlated with higher incidence of JAK/STAT pathway mutations (p<0.05), while patients with European ancestry exhibited more diversity in genetic drivers. Lastly, differential gene expression analysis indicated that variations in EBV gene expression aligned with variations in host immune response mechanisms. By examining a geographically diverse patient cohort, this study was able to demonstrate the heterogeneity of ENKTCL. Our study suggests that underlying immune signaling and genetic ancestry are prognostic in ENKTCL. Our study supports the separation of two entities derived from T and NK cells that demonstrate distinct genetics and patient outcomes.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001374","title":"High-Grade B-Cell Lymphoma: Atlas of Blood Cancer Genomes","description":"High-Grade B-cell Lymphoma (HGBCL) is a biologically aggressive and clinically heterogeneous lymphoma subtype characterized by frequent MYC rearrangements often in combination with BCL2 and/or BCL6 translocations. While both BCL2- and BCL6-rearranged HGBCLs fall under the same diagnostic category, emerging genomic and transcriptomic data suggest distinct molecular features and clinical outcomes between these subgroups. To systematically explore these differences, we comprehensively profiled the clinical and genomic landscape of HGBCL in a cohort of 53 biopsy samples. The cohort was stratified by translocation category: MYC/BCL2, MYC/BCL2/BCL6 (triple-hit, TH), MYC/BCL2/BCL6 (unconfirmed double-hit, unconfirmed TH), and MYC/BCL6. We identified numerous recurrent driver mutations and noted significant enrichment of mutations in genes such as CREBBP, BCL2, EZH2, and GNA13 in BCL2-translocated cases. Patients harboring BCL2 translocations exhibited markedly poorer overall survival, highlighting distinct biological signals potentially driven by these enriched genetic alterations. We observed clear transcriptional differences between BCL2-translocated cases and the MYC/BCL6 group, mirroring the divergent survival outcomes. Collectively, these findings emphasize the clinical and molecular heterogeneity within HGBCL and highlight the importance of integrating translocation status and mutation profiling to enhance prognostic accuracy and inform tailored therapeutic strategies.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001375","title":"Mycosis Fungoides: Atlas of Blood Cancer Genomes","description":"Mycosis fungoides (MF) is the most common primary cutaneous T cell lymphoma (CTCL). MF exists on a spectrum of indolent to aggressive forms, the latter encompassing large cell transformation (LCT) subtype and Sezary syndrome (SS). To date, molecular characterization of MF and SS disease biology is limited. Our study is the largest multi-center genomic study of MF. Through whole exome and transcriptome sequencing on a cohort of 67 patients from 15 institutions, we show that copy number variants in regions containing CDKN2A, TP53, RB1 and ZEB1 were the most common genomic alterations, concordant with findings from a previous large SS study. LCT patients had worse progression-free survival compared to their non-LCT counterparts (p<0.01). Gene enrichment studies showed that cell cycle pathways and genes involved in the G2M checkpoint were more upregulated in LCT samples compared to those without LCT. Conversely, inflammatory response via the NFkB signaling pathway was more upregulated in those without LCT. Black patients (genomic race designation) also showed worse overall survival compared to white patients, with the known driver gene ARID1A more frequently mutated in Black compared to white patients (p<0.05). These results give a better understanding of the heterogeneity of MF and highlight potential targetable pathways for patients with aggressive forms of the disease.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001376","title":"Integrative clinical and immune profiling reveals pre-infusion biomarker of CART-cell resistance","description":"Axicabtagene Ciloleucel, a CD28-based anti-CD19 CAR T-cell therapy, induces remission in approximately 50% of patients with large B-cell lymphoma (LBCL). In this study, we conducted a comprehensive analysis of patients with DLBCL treated with Axi-Cel to identify determinants of response and resistance to CAR-T cell therapy pre- and post-manufacturing of CAR-T cells.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001377","title":"Clinical Utility of Breast cancer Research by Inocras, Catholic university hospital and Samsung medical center","description":"Breast cancer remains a major global challenge. To comprehensively characterize its genomic landscape and clinical significance, we analyzed whole genome sequences from 1,364 clinically annotated breast cancers, integrating transcriptome data from most of the tumors.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-17T09:53:16.797176+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001378","title":"T Lymphoblastic Leukemia/Lymphoma: Atlas of Blood Cancer Genomes","description":"T-lymphoblastic leukemia/lymphoma (T-ALL) represents a clinically challenging group of blood cancers characterized by disparate, frequently poor outcomes. T-ALL comprises 15% of pediatric and 25% of adult lymphoblastic leukemia/lymphomas. While age is known to be a major determinant of survival following diagnosis, the biology underlying this association is not fully understood. To gain further insights into disease biology underlying the observed clinical heterogeneity, we recruited 216 cases of T-ALL and performed whole exome and transcriptome sequencing. Laboratory and clinical data including progression-free survival (PFS), overall survival (OS) and treatment regimens were collected. Our cohort included children (32%), adolescent/young adults (46%) and adults (22%). We found a strong association between older age and prognosis (OS: p=3.79e-5; PFS: p=4.53e-5). Nonsynonymous mutations and copy number changes were identified in 100% of patients. Previously reported genetic drivers including NOTCH1, FBXW7, PFH6, PTEN, BCL11B, WT1 and JAK3 occurred with similar frequency in our cohort. Select genes such as PHF6 and DNMT3A were associated with prognosis independent of age. Gene expression analysis indicated a highly proliferative disease characterized by higher expression of cell cycle-related genes in the pediatric population, whereas inflammatory response pathways were upregulated in older patients. The inflammatory signature was associated with worse PFS (p<0.05) and showed a trend to inferior OS. Our study expands understanding of genomic landscape in T-ALL across age groups. It provides new evidence for biologically distinct disease drivers associated with age and prognosis and indicates new candidate genes for inclusion in routine clinical testing.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001379","title":"Primary Cutaneous B-cell Lymphoma: Atlas of Blood Cancer Genomes","description":"PCBCLs represent a heterogeneous group of malignancies with distinct histologic and clinical profiles that include DLBCLLT, PCFCL, and PCMZL. We performed a comprehensive genomic and clinical profiling of PCBCL as part of the Atlas of Blood Cancer Genomes Project. We confirmed DLBCL-LT patients have significantly (p<0.05) worse OS and performed integrative genomic and transcriptomic analyses comparing these subtypes to identify molecular drivers of the stark outcome differences. In DLBCL-LT, mutational profiling revealed significantly higher frequencies of mutations in MYD88 and common aSHM targets including IGLL5, PIM1, and CD79B. In contrast, PCFCL showed significant enrichment of variants among genes involved in NF-kB signaling such as TNFRSF14, TNFAIP3, and NFKB2. Consistent with its aggressive clinical phenotype, DLBCL-LT exhibits frequent copy number alterations across all chromosomes, especially chromosomes 3, 11, and 18 gains, and 6q and 9p losses. We further developed a transcriptomic signature that robustly distinguished PCFCL from PCMZL. The NOTCH pathway was enriched in PCMZL and PI3K/AKT/mTOR signaling in PCFCL, underscoring distinct oncogenic mechanisms. This study reveals profound molecular divergence across PCBCLs, supports the use of RNA-based approaches in aiding the diagnosis of these tumors and identifies subtype-specific features that may inform therapeutic strategies.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001380","title":"Primary Mediastinal Large B-cell Lymphoma: Atlas of Blood Cancer Genomes","description":"Primary mediastinal large B-cell lymphoma (PMBL) is a subtype of non-Hodgkin B-cell lymphoma, most frequently occurring in young adults. We characterized 85 PMBL cases from the Atlas of Blood Cancers Genome Project. The cohort was predominantly young (median age 34) and female (58%), and included diverse racial backgrounds. Most individuals presented with low-stage disease, favorable ECOG performance status, with high overall survival at last follow-up (89%). Whole transcriptome sequencing of 49 PMBL cases revealed gene expression profiles distinct from diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). PMBL cases exhibited significantly higher expression of thymic B cell-associated genes (p=0.032) identifying these cells as a potential cell of origin for PMBL. DNA sequencing confirmed recurrent mutations in JAK/STAT, NF-κB signaling, and DNA damage response pathways and CIITA rearrangements. We also identified frequent aberrant somatic hypermutation (aSHM) affecting known target genes. Although PMBL generally demonstrates excellent outcomes, aSHM-positive cases exhibited significantly worse progression-free survival (p=0.03), suggesting aSHM as a potential adverse prognostic marker. These findings further refine the genomic landscape of PMBL and provide new insights into the biology of this neoplasm with implications for prognostic stratification.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001381","title":"Rosai-Dorfman Disease: Atlas of Blood Cancer Genomes","description":"Rosai-Dorfman disease (RDD) is a rare histiocytic disorder, most prevalent in children and young adults. The diagnosis of RDD and other histiocytic disorders including Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) can be challenging as it relies mostly on immunohistochemistry (IHC) of infrequently assayed markers. Little is known about how the gene expression profiles of histiocytic disorders correlate with IHC diagnostic markers, activation of different oncogenic pathways, or components of the microenvironment. To address this gap, we performed whole transcriptome sequencing on samples from 23 RDD, 4 ECD and 9 LCH patients, enabling us to examine differential gene expression, tumor microenvironment signatures and gene set enrichment between the different histiocytic neoplasms. Gene expression levels by RNA sequencing correlated well with IHC results for diagnostic markers for all three diseases, highlighting the ability to use RNA-based approaches including RNAseq for diagnosing these tumors. RDD samples showed strong enrichment of gene sets related to B cells and the IL27 pathway. In contrast, LCH showed enrichment of gene sets related to resting dendritic cells and the HNFA3A pathway. Cell type deconvolution showed enrichment of memory B cells, plasma cells and CD8+ T cells in the RDD microenvironment and enrichment of dendritic cells in the LCH microenvironment. In summary, our study demonstrates the utility of RNA sequencing in helping to distinguish histiocytic disorders, as well as differential activation of oncogenic pathways and tumor microenvironment between RDD, ECD and LCH, that sheds light on the pathogenesis and overall disease biology of these rare disorders.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001382","title":"WES analysis of paired tumor and non-tumoral DNA of 4 patients with non-muscle-invasive bladder cancer","description":"We performed WES of tumor DNA and non-tumoral DNA (extracted from PBMC) of 4 patients with non-muscle invasive bladder cancer, who after the tumor resection went on to receive BCG treatment as they had high-risk disease. In order to identify tumor-specific mutations that could give rise to patient-specific neo-epitopes, we performed paired WES of tumor and non-tumoral DNA for each patient. For patient UC2, 3 different tumors were resected at the same time and DNA from these 3 tumors were sent separately for WES.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-03T15:42:18.446416+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001383","title":"bulk RNAseq analysis of tumor from 3 non-muscle-invasive bladder cancer patients","description":"We performed screenings of patient-specific neo-epitopes by tumor-infiltrating CD8+ T lymphocytes of 4 non-muscle invasive bladder cancer patients. After the tumor resection, these patients went on to receive BCG treatment as they had high-risk disease. In order to select the neo-epitopes, we performed bulk RNAseq of the bladder tumor to select the mutated genes that were expressed in the tumor (TPM >1). For patient UC2, 3 different tumors were resected at the same time and RNA from these 3 tumors were sent separately for RNAseq. For patient UC4, no RNA was available, so this patient is not included in this study.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-03T15:42:20.99943+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001384","title":"scRNAseq analysis of CD8 T cells infiltrating the bladder and tumor of 4 non-muscle-invasive bladder cancer patients, before and after BCG treatment.","description":"We performed scRNAseq analysis of CD8 T cells infiltrating the bladder and tumor of 4 non-muscle-invasive bladder cancer patients, before and after BCG treatment. In order to identify tumor-specific T cells, we selected CD8 T cells that were enriched in the tumor of the patient. We also selected CD8 T cells appearing in the bladder after BCG treatment, with the hypothesis that BCG treatment stimulates tumor-specific CD8 T cells. Next, we cloned the TCR of these T cells in a Jurkat cell line and tested these TCR for recognition of tumor-specific antigens.\r\n","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-03T15:42:15.606668+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001385","title":"Whole-Exome Sequencing of Tumor Biopsies from a Colorectal Cancer Patient with Two Distinct Primary Tumors and Matched Metastases","description":"Colorectal cancer (CRC) is a heterogeneous disease in which rare genetic alterations, such as neurotrophic receptor tyrosine kinase (NTRK) fusions, have emerged as clinically relevant therapeutic targets. Here, we report the case of a 69-year-old man with an advanced colorectal carcinoma comprising two intermixed but histologically distinct components: a predominant (>90%) poorly differentiated solid carcinoma and a conventional adenocarcinoma with mucinous features. Whole-exome sequencing (WES) of microdissected tumor regions (two primary tumors and two matched metastases) along with germline DNA analysis revealed profound genetic divergence between the two tumor components. This case illustrates the coexistence of two genetically independent yet spatially inseparable CRCs following distinct evolutionary trajectories—one driven by an NTRK1 fusion and microsatellite instability (MSI), and the other by canonical KRAS and SMAD4 alterations.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-14T15:58:10.910549+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001386","title":"Treatment of CAR T cells with immunomodulatory metabolites","description":"Anti-Her2-CAR T cells produced from T cells derived from healthy human donors were treated with DMSO (control) or either of the immunomodulatory metabolites indole‐3‐carboxaldehyde (ICA), valeric acid (VA) and isovaleric acid (IVA) to assess effects on CAR T cell function.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-29T09:35:46.267553+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001387","title":"Whole genome sequencing data of paediatric T cell acute lymphoblastic leukemia (T-ALL)","description":"T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy accounting for approximately 15–25% of pediatric and adult ALL cases. Despite significant therapeutic improvements over the last decade, the prognosis of T-ALL remains less favorable than that of B-ALL, with 5-year EFS and OS of around 76–82% and 80–88%, respectively, depending on the treatment protocol used. T-ALL patients often suffer from failure of induction therapy or early relapse, which is associated with a dismal prognosis. Approximately 10–15% of T-ALL patients experience relapse, and survival after relapse is poor.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-10-31T15:08:18.99056+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001388","title":"Iron related tumorigenesis in desmoid fibromatosis ","description":"Decipher the role of iron endocytosis in the oncogenesis of primary mesenchymal tumors","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001389","title":"Whole genome sequencing of human colorectal cancers, tumour organoids and paired normal samples","description":"Colorectal cancer is the third most common cancer and the second leading cause of cancer-related deaths worldwide. Our consortium aims to identify robust biomarkers for clinical management and novel molecular targets for therapeutic interventions. Using whole-genome sequencing on human colorectal cancers, tumour organoids and paired normal samples, we aim to refine molecular pathways of carcinogenesis and to identify markers to stratify patients for specialized treatment.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001390","title":"ISCAPE V(D)J libraries from HA-specific single memory B cells and personalized IGM, IGK, IGL V(D)J repertoire sequencing of four Influenza A exposed individuals","description":"Peripheral blood mononuclear cells were used to produce paired, full-length IGM, IGK and IGL V(D)J libraries from HA-binding single memory B cells using the ISCAPE (Individualized Single Cell Analysis of Paired Expressed antigen receptors) technique. Locus-specific multiplexed nested PCR with 5’ leader IGHV/IGKV/IGLV and 3’ constant IGG/IGK/IGL primer mixtures was performed before well and plate indexing and paired chain sequencing with an Illumina MiSeq instrument. Expressed total IGM, IGK and IGL V(D)J libraries from each donor were generated to define personalized IG allele content. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-26T12:19:43.471228+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001391","title":"10x Genomics FLEX single cell RNA-seq of three intestinal tissues and peripheral blood from a healthy donor","description":"Fixed single cell RNA-seq of terminal ileum (IL), transverse colon (TC), rectum (RE), leukocytes (BL) collected from a healthy donor. The biopsies were firstly fixed with 4% formaldehyde to preserve fragile cell populations like epithelial cells and neutrophils. Transcriptome was obtained using a probe hybridization to detect 18,099 human mRNA. Transcriptome information from 6,948 (IL), 4,448 (TC), 5,271 (RE) and 6,883 (BL) single cells were obtained.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-12T14:57:39.808708+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001392","title":"Transcriptome analysis of a novel human iPSC-derived 3D cortical tissue model – 2D versus 3D co-culture comparison","description":"Single-cell RNA-seq analysis of human iPSC-derived microglia/astrocytes/neurons in a novel, human in vitro 3D cortical tissue model, as well as 2D co-cultures for comparison. Samples include distinct conditions (each as biological triplicates):\r\n- wild-type cells from 2D or 3D co-cultures after 3 months of culturing (2D_WT, 3D_WT)\r\n- knock-in cells from 2D or 3D co-cultures carrying three familial AD mutations in the APP gene (Swedish, Iberian, Arctic; introduced by CRISPR/Cas9-mediated knock-in) after 3 months of culturing (2D_KI, 3D_KI)\r\n- 2D and 3D KI cultures treated with Bumetanide (KI_bum) or BACE IV (KI_bace) inhibitor\r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-23T16:07:49.798489+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001393","title":"ImmunAID","description":"The ImmunAID study is a multi-center research program aimed at improving the diagnosis and understanding of systemic autoinflammatory diseases. The study integrates immunological, and molecular data from patients across several European cohorts. Its objective is to identify biomarkers and biological pathways that characterize disease mechanisms and help differentiate between inflammatory conditions.\r\nThis project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 779295.\r\n\r\nThe project has generated genomic datasets, which are available through the European Genome-phenome Archive (EGA). In addition, it has produced several non-genomic datasets, listed below.\r\nAll datasets have been fully anonymized in accordance with applicable ethical and regulatory frameworks.\r\nThese non-genomic data are available upon request.\r\n\r\nTo request access to these datasets, please contact:\r\nimmunaid2024@gmail.com\r\nYour request will be studied by the Data Access Committee, and data will be made available upon approval.\r\n\r\nNon-genomic datasets available:\r\nFlow cytometry (general immune phenotype) — Dataset ID: ICKD2021569, size: 23 GB, 342 patients\r\nSomascan proteomics data — Dataset ID: ICKD2021570, size: 59 MB, 444 patients\r\nELISA panel (Ferritin, CRP, HO1, IL-1B, IL-6, IL-8, IL-10, IL-12, IL-18, IFN-γ, TNF-α) — Dataset ID: ICKD2021571, size: 295 KB, 439 patients\r\nMass spectrometry (MS/MS) — Dataset ID: ICKD2021572, size: 1.8 TB, 447 patients\r\nELISA (CRP/ SAA) — Dataset ID: ICKD2021573, size: 321 KB, 443 patients\r\nFlow cytometry (inflammasome activity) — Dataset ID: ICKD2021574, size: 899 KB, 307 patients\r\nPlasma lipidomics — Dataset ID: ICKD2021575, size: 1.1 MB, 427 patients\r\nUrine lipidomics — Dataset ID: ICKD2021576, size: 833 KB, 368 patients\r\nELISA (alarmins) — Dataset ID: ICKD2021577, size: 129 KB, 108 patients\r\nELISA (IL-18 / IL-1) — Dataset ID: ICKD2021578, size: 271 KB, 330 patients\r\nFlow cytometry (NK cell alterations) — Dataset ID: ICKD2021579, size: 14 GB, 216 patients\r\nChemokine measurements — Dataset ID: ICKD2021580, size: 489 KB, 404 patients\r\nLuminex (multiple analyte measurements) — Dataset ID: ICKD2021581, size: 759 KB, 369 patients\r\n","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-17T15:38:09.89237+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001394","title":"Calcoco2 IP-MS and RNA-Seq","description":"CALCOCO2 (Calcium binding and coiled-coil domain 2), also known as NDP52, is a mitophagy adaptor implicated in mitochondrial quality control. Our previous work showed CALCOCO2 regulates insulin granule turnover in pancreatic beta cells, supported by LC3 and insulin colocalization via immunofluorescence. However, its precise molecular mechanisms underlying the function of CALCOCO2 have not yet been discovered. Here, we newly identified mitophagy-associated binding partners of CALCOCO2 using proteomics and co-immunoprecipitation in human beta cell line EndoC-βH1. We observed an increase in autophagic flux upon CALCOCO2 siRNA knockdown combined with lysosomal inhibitor chloroquine (CQ) treatment. To assess mitochondrial function, we performed a Seahorse Mito Stress Test, which revealed significantly reduced oxygen consumption rate in CALCOCO2-depleted cells. Double knockdown of CALCOCO2 and autophagy-related genes ATG5 or BECN1 rescued the insulin content reduction caused by CALCOCO2 silencing, suggesting that loss of CALCOCO2 triggers excessive autophagy leading to insulin loss. Finally, cells stably expressing a clinically relevant type 2 diabetes (T2D)-associated risk variant identified from GWAS exhibited hyperactivated autophagy and decreased insulin content and secretion. Our findings highlight the key role of CALCOCO2 in maintaining mitochondrial function and insulin granule homeostasis via autophagy in pancreatic beta cells, linking its dysfunction to T2D pathogenesis.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001395","title":"Targeted sequencing data of regulatory regions in 200 Spanish ASD trios","description":"This study consists of genomic sequencing data obtained through targeted sequencing of regulatory regions (85,394 human cCREs from ENCODE v2, version 2, https://screenv2.wenglab.org/) in 200 ASD (Autism Spectrum Disorder) trios (father and mother unaffected and proband affected). The aim of the project is to detect genomic variants (rare and inherited variants) in regulatory regions that contribute to autism.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-08T17:06:41.680091+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001396","title":"Single-cell transcriptomics analysis of anti-aging compounds","description":"Single-cell transcriptomics analysis of PBMCs treated with selected anti-aging compounds at different time points","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001397","title":"scRNA-seq of a 3D human cortical tissue model from human iPSCs exploring WT versus APP KI genotypes as well as Abeta/Aducanumab treatments","description":"Single-cell RNA-seq analysis of human iPSC-derived microglia/astrocytes/neurons in a novel, human in vitro 3D cortical tissue model across cell lines, distinct genotypes (WT and APP KI) and in presence of Abeta/Aducanumab treatments. Samples include distinct conditions as described in the Study section. The dataset was generated using the BD Rhapsody technology and sequenced paired-end with Illumina NovaSeqX. Information on the multiplexing of samples is reported in the Analyses section.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-23T16:07:51.720868+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001398","title":"Error-Corrected Next-Generation Sequencing Rectal Mucus","description":"Error-corrected next-generation sequencing of rectal mucus samples from patients suspected to have colorectal cancer. This is 1 of 4 sequencing experiments on the same sample type.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-16T10:31:11.464709+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001399","title":"Bulk transcriptomics analysis of anti-aging compounds","description":"In this study PBMC transcriptome was analysed in response to the treatment with selected compounds with potential anti-aging effect at different concentrations and timepoints","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001400","title":"single cell RNA-seq of small cell lung cancer tumors","description":"This study investigated the transcriptomic profile of small cell lung cancer from 10 patients. Tumors were rapidly dissociated after the surgical procedure. Libraries were constructed using the VDJ NextGEM v1.1 10x Genomics Chromium kit. Samples were sequenced on a NextSeq 550 sequencer (Illumina).","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-17T10:59:09.612161+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001401","title":"single cell RNA-seq of small cell lung cancer circulating tumor cells","description":"This study investigated the transcriptomic profile of circulating tumor cells from three small cell lung cancer patients. CTCs were enriched from the blood of three SCLC patients using the CTC-iChip followed by magnetic depletion of RBCs. The enriched samples were processed with the 10x Genomics Chromium platform (Chromium GEM-X Single Cell 3' Kit v4) and sequenced on a NextSeq 2000 system.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-17T10:59:11.192401+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001402","title":"Insights into BRCA1 and TP53 associated breast cancer development from integrated whole genome analysis of mouse model mammary tumors","description":"Germline mutations in BRCA1 are a leading cause of hereditary breast cancer. We generated Brca1;Trp53 double conditional knockout (CKO) and Trp53 single CKO mouse models, both with either one or two copies of Trp53 deleted by Cre. We used whole-genome sequencing and optical genome mapping to interrogate the genomes of the resulting mammary tumors. Our comprehensive genomic analyses show that the Brca1;Trp53-CKO tumors recapitulate major genomic features of the human BRCA1 breast samples indicative of conserved fundamental mutational processes. This study also provides new insights into the genetic mechanisms of tumor development with potential implications for the treatment of BRCA1 cancers.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-06T13:21:29.402072+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001403","title":"NeoRhea Bulk RNA and Single nuclei RNA & ATAC","description":"The aim of this study is to compare baseline and surgery samples of ER+/HER2- early breast cancer patients. Patients have been treated with endocrine therapy in combination with palbociclib. Samples have been collected pre and post treatment.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-09T10:56:13.279059+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001404","title":"Single-cell transcriptomic analysis of human PBMCs before and after dietary intervention","description":"In this study we analysed with the SeqWell S3 technology the trascriptome of single cells from human PBMCs from donors taking part in a dietary intervention study. Samples were obtained before dietary intervention and six weeks after.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001405","title":"Chromosome centromere copy number amplification associated with exceptional response in HER2-positive metastatic breast cancer patients","description":"Metastatic breast cancer (MBC) is generally an incurable neoplasm. A small cohort of patients with HER2-positive MBC, however, achieve such prolonged remission without relapse following anti-HER2 therapy and chemotherapy, that it is speculated they might be cured. The genomes of such exceptional responders (ExR) might provide insights into the underlying mechanisms for their extreme drug sensitivity. \r\nPatients with an OS>60 month  and no evidence of relapse were defined as ExR, patients with OS>60 months but with relapse or progressive disease were defined as exceptional survivors (ExS), patients with OS<60 months were defines as short-term responders (STR). Whole genome sequencing (WGS) was performed on 12 ExR, 4 ExS, and 11 STR tumors with their matching controls. \r\nThe tumors from ExR patients had statistically significant differences in the centromeric landscape with ExR tumors harboring higher copy number (CN) compared to the ExS and STR. However, ExR tumors had non-significant increase in CN compared to ExS and STR overall. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001406","title":"Single-nucleus brain transcriptomics reveals microglia dysfunction in Multiple System Atrophy","description":"Multiple System Atrophy (MSA) is a rare, age-related neurodegenerative disease that shares clinical and pathological features with Parkinson’s disease (PD) but presents a more devastating disease course. To elucidate the distinct cellular pathophysiology underlying multiple system atrophy (MSA) or Parkinson's disease (PD), we performed single-nucleus RNA sequencing on postmortem striatal brain tissue from 7 MSA and 12 PD patients, and 10 non-neurological cases. Using 10x Genomics Chromium Next GEM Single Cell 3' Reagent Kits v3.1, we isolated 130k nuclei covering all major cell types of the striatum. We performed state-of-the-art bioinformatic analyses on the data followed by orthogonal analyses to validate our findings. We identified a disease-specific activation of microglia cells distinguishing the two diseases and possibly explaining some of the detrimental effects observed in both.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-17T17:19:13.372777+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001407","title":"Dissecting immunomodulatory capacity of chemotherapy to enhance sensitivity to anti-PD1 in metastatic TNBC: final results of the TONIC-1 and TONIC-2 trials","description":"Given the modest efficacy of anti-PD1 in metastatic triple-negative breast cancer (mTNBC), strategies to improve immunotherapy responses are urgently needed. Stage I of the TONIC-1 trial identified low-dose doxorubicin and cisplatin as promising induction treatments to prime the tumor microenvironment (TME) prior to anti-PD1. The expansion (stage II) of the TONIC-1 and the TONIC-2 trials aim to validate the immunomodulatory capacity of these induction regimens independently. We dissect the remodelling of the TME by these immunomodulatory approaches using RNA-sequencing and highly multiplexed imaging (MIBI). 97 patients were randomized to either 2-week induction with doxorubicin or cisplatin followed by nivolumab or nivolumab without induction. While induction with cisplatin (29% free of progression at 12 weeks) was considered successful based on Simon’s two-stage design, the doxorubicin cohort was not (24% free of progression at 12 weeks). However, median PFS was similar for the cohorts. Upon doxorubicin induction, immune-related processes were not significantly enriched, except for an increase in PDL1+ CD8 T cell fraction (determined by MIBI). Cisplatin induction stimulated immune-related pathways, antigen presentation, TME-reorganization towards an immune-active state, and immune checkpoint expression. Our observations can inform the development of novel immunomodulatory strategies, especially regarding platinum as a potential immunogenic chemotherapy. \r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001408","title":"Khoe-San Genome Project","description":"The dataset contains BAM files of whole genome sequencing data of African Khoe-San population (n=169, 30X coverage) recruited from South Africa and Namibia. The population captured the true extent of human genetic diversity as represent the earliest diverged human population. The project described a detailed divergence of human population and identified positive selections associated forager lifestyles in Khoe-San population. These findings emphasise an inclusive catalogue with better representation of the earliest human genomic diversity to better advance biomedical research.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-27T17:31:24.581815+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001409","title":"Human Dicer is required for cell-intrinsic immunity to self-dsRNA","description":"Self-derived double-stranded RNAs (self-dsRNAs) can activate cell-intrinsic innate immune responses and contribute to autoinflammation. We uncover an essential role for human Dicer in innate immune responses to self-dsRNA. Loss of Dicer disrupts RIG-I-like receptor-dependent type I interferon (IFN-I) induction and activation of both the PKR and OAS1-3/RNAse L pathway in conditions where self-dsRNA accumulates, such as cells lacking ADAR1, PNPase, hnRNPC, or MPP8. In contrast, Dicer does not affect the IFN-I response triggered by exogenous dsRNA. Dicer interacts with LGP2, G3BP1, and Staufen1 and loss of these proteins similarly impairs IFN-I induction by self-dsRNAs. Depletion of Dicer and G3BP1 reduces the accumulation of immunostimulatory self-dsRNAs, while depletion of Dicer and Staufen1 prevents MDA5 oligomerization. We conclude that Dicer regulates self-dsRNA availability and sensing, aided by G3BP1 and Staufen1, respectively. Our findings highlight a non-canonical role for Dicer in innate immune activation by self-dsRNA and pinpoint new drug targets in autoinflammatory disorders.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-09T18:08:46.604108+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001410","title":"Splicing signature analysis of RNU2-2 samples","description":"Dominant pathogenic variants in the snRNA RNU2-2 were recently reported as a cause of neurodevelopmental disorders. \r\nIn our study we identified additional individuals with dominant variants (n.4G>A and n.35A>G) and we also identified biallelic variants as a novel frequent cause of neurodevelopmental disorder. We obtained blood samples and performed short-term lymhocytes cultures for 19 cases (5 n.4; 5 n.35; 9 biallelic). We generated exome-capture RNA-Seq for these cases that we compared to 49 controls (probands affected from a neurodevelopmental disorder but without RNU2-2 variants). We observed that RNU2-2 variants mainly disturb alternative exon skipping, although affecting different exons.\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-17T17:20:32.028963+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001411","title":"Molecular Landscape of Hypertrophic Cardiomyopathy Across Disease Stages and Genotypes","description":"Hypertrophic Cardiomyopathy (HCM) is marked by asymmetric cardiac wall thickening, enhanced contractility, diastolic dysfunction, and fibrosis. Pathogenic sarcomere gene variants cause HCM, but comparable abnormalities occur in patients with unexplained disease albeit with fewer adverse events. \r\nWe applied single-nucleus RNA sequencing to investigate how genetic and unexplained HCM affect early disease mechanisms and to contrast HCM with dilated cardiomyopathy (DCM). \r\nThis EGA dataset contains HCM and control data. DCM and additional control snRNA-seq data, integrated in this study, are available under the EGA dataset accession number: EGAD00001009292.\r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-25T14:04:11.350501+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001412","title":"Axon guidance deficits in a human sensory neuron model of Fabry disease","description":"We compared gene expression levels of human iPSC derived sensory neurons between an isogenic GLA knockout line and its healthy control as an in Fabry disease in vitro model.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001413","title":"TGF-β signaling mediates microglial resilience to spatiotemporally restricted myelin degeneration","description":"Microglia survey and regulate central nervous system myelination during embryonic development and adult homeostasis. However, whether microglia-myelin interactions are spatiotemporally regulated remains unexplored. By examining spinal cord white matter tracts, we found that myelin degeneration was particularly prominent in the dorsal column (DC) during normal aging. This was accompanied by molecular and functional changes in DC microglia as well as an upregulation of TGF-β signaling. Disrupting TGF-β signaling in microglia led to unchecked microglial responses and myelin loss in the DC, accompanied by neurological deficits exacerbated with aging. snRNA-seq revealed the emergence of a TGF-β signaling-sensitive microglial subset and a disease-associated oligodendrocyte subset, both spatially restricted to the DC. We further discovered that microglia rely on a TGFβ autocrine mechanism to prevent damage of myelin in the DC. These findings demonstrate that TGF-β signaling is indispensable for maintaining microglial resilience to myelin degeneration in the DC during the aging process. This highlights a previously unresolved checkpoint mechanism of TGF-β signaling with regional specificity and spatially restricted microglia-oligodendrocyte interactions.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001414","title":"RNA sequencing of pituitary neuroendocrine tumors (PitNETs)","description":"This study reports a multiomic analysis of pituitary neuroendocrine tumors.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-08T15:19:16.560794+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001415","title":"Cell-free DNA methylome and fragmentome analysis for disease relapse monitoring in patients with Ewing Sarcoma","description":"We conducted whole-genome and methylome sequencing of cfDNA from 87 serial samples of 23 patients with EwS and 3 patients with CIC-rearranged sarcoma (CIC). With EwingSign, a new machine learning model, we identified EwS or CIC in a test set for 11 out of 16 patients at diagnosis and 15 out of 18 clinically confirmed relapse events. 0 out of 24 non-cancer controls were detected positive with EwingSign.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-08T17:00:43.044742+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001416","title":"Tumor cells metabolically resist immune-checkpoint therapy by macrophage efferocytosis-mediated fatty acid recycling","description":"Tumor cells metabolically adapt to the nutrient-deprived tumor microenvironment (TME). However, the metabolic plasticity underlying immune-checkpoint blockade (ICB) adaptation remains unclear.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-28T09:39:03.060827+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001417","title":"Oligodendroglia as functional effectors of Multiple Sclerosis risk variants (iPS derived hOPC scCRISPRi/a-seq)","description":"Study of the regulatory effect of a selection Multiple Sclerosis (MS) associated SNPs applying high-throughput functional genomics in human induced pluripotent stem cell-derived oligodendroglia (iPS-derived hOPCs). Selected cis-regulatory elements were assesed with lentiviral-based pooled single cell (sc)CRISPR-seq screens. CRISPRi/a (dCas9-KRAB and dCas9-p300 respectively) was performed, in combination with direct-capture Perturb-sequencing single-guide RNA (sgRNA) and droplet-based single-cell RNA-seq, allowing high sgRNA capture efficiency and identification of possible transcriptional regulatory mechanisms at a single cell/sgRNA level. ","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-09T11:02:52.248712+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001418","title":"single nuclei multiomics (ATAC-RNA) of KOLF2.1J human induced pluripotent stem cells-derived differentiated dopaminergic neurons","description":"We processed nuclei from hIPSCs differentiated optimized protocols for generating dopaminergic neurons. Cells differentiated with a first iteration were RNA and ATAC-sequenced, to understand our protocol caveats to address for optimization. Cells differentiated with a second protocol and in vivo were RNA-sequenced to validate the identities of our cells. \r\n\r\n","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-09T11:02:50.861397+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001419","title":"RNA seq data of 2 lung cancer samples prepared using 2 different RNA-seq library preparation protocols","description":"Raw data used for generation of the results in the Vardetector manuscript – “.bam” files of RNA-seq data of tumor samples of 2 patients prepared with 2 different library preparation protocols (exome-capture and ribodepletion –> 4 “.bam” files in total). The submission also contains the somatic mutations “.vcf” files (4 in total, however 2 unique). Moreover, also an output of the Vardetector module (“.csv” file with the number of reads above the mutations of interest) is present in the submission (4 “.csv” files in total).","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-02T12:49:24.387639+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001420","title":"Intrapatient tumor heterogeneity and clonal evolution in metastatic salivary gland cancer: an autopsy study","description":"This data contains DNA sequencing data of an autopsy study in patients with salivary gland cancer. Whole-genome sequencing was performed on multiple spatially separated tumor samples per patient (4-7 per patient) and healthy control samples.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-27T17:27:23.953511+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001421","title":"Bulk RNASeq of metastatic colorectal cancer organoids with ATOH1 knockout","description":"Bulk RNA sequencing was performed on mCRC organoids subjected to cetuximab treatment, comparing ATOH1 knockout and control conditions. The dataset is intended to elucidate the contribution of ATOH1-regulated secretory cell population to cetuximab persistence mechanisms.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-11T16:53:26.552103+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001422","title":"Bulk RNASeq of metastatic colorectal cancer organoids treated with crenigacestat alone or in combination with cetuximab","description":"Bulk RNA sequencing was performed on mCRC organoids cultured under untreated conditions or treated with crenigacestat alone or in combination with cetuximab. This dataset was generated to investigate the transcriptional changes associated with combination therapy and to compare these profiles with the adaptive responses observed following cetuximab monotherapy in the corresponding ATOH1 wild-type and knockout organoid models.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-11T16:53:28.285764+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001423","title":"CFTR Gene Variant Detection in Moroccan Individuals via Nanopore Long-Read Sequencing","description":"This study consists of sequencing the whole CFTR gene (coding and non-coding regions) using Oxford Nanopore on Moroccan CF patients","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-02T11:43:08.090891+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001424","title":"PHRT study of longitudinal sampling in ovarian cancer","description":"High-grade serous ovarian cancer presents significant challenges due to its poor prognosis and high heterogeneity, both of which complicate treatment responses. This project aims to understand intra-patient tumor evolution by investigating different sampling sites (primary and metastatic) at the time of diagnosis and during disease recurrence.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-02T16:07:10.970772+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001425","title":"Long read sequencing in MinIon enriched nucleotide repeat expansions","description":"comparison of the detection using Minion Oxford Nanopre sequencing, case 01012MA, using a set of 36 crRNA probes","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-27T10:20:02.321657+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001426","title":"Long read sequencing of nucleotide repeat expansions in Flongle Oxford Nanopore","description":"sequencing in flongle after enrichment using a set of 36 crRNA probes, casse 01012MA","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-27T10:20:02.321657+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001427","title":"Comparison of crRNA design for long read sequencing of enriched nucleotide repeat expansions in Flongle Oxford Nanopore","description":"Comparision of the design with 36 or 23 crRNA probes for the enrichment on case 01006GT","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-27T10:20:02.321657+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001428","title":"Long read sequencing of nucleotide repeat expansions in Flongle Oxford Nanopore","description":"Long read sequencing in CRISPR Cas9 enriched nucleotide repeat expansions in Flongle Oxford Nanopore, after enrichment using a set of 23 crRNA","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-27T10:20:02.321657+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001429","title":"Single-cell genotype-to-phenotype (scG2P) data of single nuclei from cell line mixing experiment and six donors","description":"We developed Single-cell genotype-to-phenotype (scG2P) to profile mutations in driver gene hotspots and capture mRNA targets of interest, validating this assay in a cell line mixing experiment of KYSE-270, KYSE-410, and HCT-116, and applied the assay to esophageal biopsy samples from six donors. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-19T13:15:04.708777+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001430","title":"Longitudinal multi-omics support immunotrhrombosis as the molecular force behind increased post-acute complication risk ","description":" Whole blood transcriptome profiles in severe COVID-19 patients (n=81) across three timepoints: A) 1st day of hospital admission, B) one month (38.46 ± 12.89 days) post-hospitalization, and C) three months post-infection (96.29 ± 13.81 days post-hospitalization). 62 patients had blood collected at all three timepoints (19 patients have transcriptome data from two timepoints (acute phase (timepoint A) and recovery phase (timepoint B or C)), 224 blood transcriptomes in total.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-26T15:13:34.777146+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001431","title":"Fragmentomics analyses of urinary cell-free DNA permit multi-urologic cancer detection and reduction in tissue biopsies for prostate cancer","description":"This study demonstrated the close association between urinary cell-free DNA (cfDNA) methylation status and the fragmentation patterns in healthy controls and patients with various diseases. Fragmentomics-based methylation analysis (FRAGMA) enables accurate estimation of methylation levels in urinary cfDNA, which is proved by paired bisulfite sequencing and non-bisulfite sequencing data. FRAGMA showed high accuracy in deducing tissue-of-origin of urinary cfDNA in transplantation patients and pregnant women. Moreover, FRAGMA showed great potential in the detection and classification of multiple cancers from the urinary system, including bladder, kidney, and prostate cancer. This study demonstrated that FRAGMA could be applied to improve current diagnostic strategies based on urine samples.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-01T11:29:21.000504+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001432","title":"HaJo Cell Line WES Data","description":"This study includes whole-exome sequencing data of the HaJo cell line and the corresponding patient and PDX samples.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001433","title":"HaJo Cell Line WTS Data","description":"This study includes Whole-Transcriptome Sequencing Data of the HaJo cell line including the corresponding patient and PDX data. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001434","title":"HaJo Cell Line BCRseq Data","description":"This study includes BCRseq data from the HaJo cell line as well from the corresponding patient and PDX samples.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001435","title":"Gut microbiome dysbiosis drives cartilage damage in Spondyloarthritis","description":"Spondyloarthritis (SpA) is an immune-mediated inflammatory disease characterized by concurrent gut and joint inflammation. By integrating intestinal biopsy amplicon sequencing with fecal metagenomic and metabolomic profiling in 119 treatment-naïve SpA patients, the study identified a 10-fold increase in the pro-inflammatory B2 enterotype, marked by depletion of butyrate producers and enrichment of Ruminococcus gnavus, Dialister invisus, and Anaerostipes hadrus. These microbial alterations were linked to disease diagnosis and activity, independent of gut inflammation. Longitudinal and gnotobiotic mouse experiments demonstrated that B2-type dysbiosis predicts non-response to treatment and causally enhances arthritis severity and cartilage damage, establishing the B2 enterotype as a pathogenic driver in SpA.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001436","title":"High-depth whole genome sequencing of 51 premalignant breast lesions","description":"Ductal carcinoma in situ (DCIS) is a non-obligate precursor lesion of breast cancer, representing 20-25% of newly diagnosed breast cancer lesions. It is currently not possible to predict which DCIS patients will progress to invasive breast cancer. The samples deposited here are part of a larger study using high-depth whole-genome sequencing (WGS) to investigate the somatic mutation genomic landscape of DCIS. Comprehensive evaluation of DCIS genomes aims to uncover biological insights into breast cancer progression and potential opportunities to stratify DCIS patients for personalised treatment options or active surveillance.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-27T12:14:21.543066+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001437","title":"RNAseq: Acquired non-permissive bone marrow microenvironment impairs hematopoietic stem cell proliferation and maintenance and B-cell development post-HSCT","description":"Defects in B-cell reconstitution upon hematopoietic stem-cell (HSC) transplantation (HSCT) are a common observation, yet the mechanism remains unexplained. The bone marrow (BM) stroma, including mesenchymal stromal cells (MSCs), guides HSC maintenance and B-lymphopoiesis by secreting crucial cytokines. We report acquired, permanent, selective and complete B-cell deficiency in the context of full donor-chimerism in a patient with X-linked lymphoproliferative disease and aimed to identify the contribution of the BM-microenvironment in disrupted B-cell reconstitution post-HSCT. We studied longitudinal BM samples from the patient and his identical twin, both of whom underwent HSCT with the same donor with opposite outcomes in B-cell reconstitution. In the index patient BM, we observed progressive loss of proliferation of HSCs and a selective block at the pre-BI cell stage. In vitro modeling studies showed limited survival of patient-HSCs and a relative accumulation of pre-B cells. Patient-derived MSCs failed to support survival and proliferation of HSCs and B-cell development of healthy-HSCs which was correlated with reduced CXCL12 levels. Using bulk RNA-sequencing of MSCs and in vitro functional studies, we showed global changes in the patients’ MSCs and a progressive loss of CXCL12 expression. Indeed, survival of patients HSCs improved supplementing in vitro development culture with CXCL12, suggesting a contribution of defective CXCL12 signaling to the phenotype. In summary, our data show that an acquired defect in the BM-stromal microenvironment and exhaustion of HSCs and committed progenitors may cause a permanent non-permissive state for normal B-cell development.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-24T12:10:50.58091+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001438","title":"ATAC-seq: Acquired non-permissive bone marrow microenvironment impairs hematopoietic stem cell proliferation and maintenance and B-cell development post-HSCT","description":"Defects in B-cell reconstitution upon hematopoietic stem-cell (HSC) transplantation (HSCT) are a common observation, yet the mechanism remains unexplained. The bone marrow (BM) stroma, including mesenchymal stromal cells (MSCs), guides HSC maintenance and B-lymphopoiesis by secreting crucial cytokines. We report acquired, permanent, selective and complete B-cell deficiency in the context of full donor-chimerism in a patient with X-linked lymphoproliferative disease and aimed to identify the contribution of the BM-microenvironment in disrupted B-cell reconstitution post-HSCT. We studied longitudinal BM samples from the patient and his identical twin, both of whom underwent HSCT with the same donor with opposite outcomes in B-cell reconstitution. In the index patient BM, we observed progressive loss of proliferation of HSCs and a selective block at the pre-BI cell stage. In vitro modeling studies showed limited survival of patient-HSCs and a relative accumulation of pre-B cells. Patient-derived MSCs failed to support survival and proliferation of HSCs and B-cell development of healthy-HSCs which was correlated with reduced CXCL12 levels. Using bulk RNA-sequencing of MSCs and in vitro functional studies, we showed global changes in the patients’ MSCs and a progressive loss of CXCL12 expression. Indeed, survival of patients HSCs improved supplementing in vitro development culture with CXCL12, suggesting a contribution of defective CXCL12 signaling to the phenotype. In summary, our data show that an acquired defect in the BM-stromal microenvironment and exhaustion of HSCs and committed progenitors may cause a permanent non-permissive state for normal B-cell development.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-11-24T12:10:50.58091+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001439","title":"CLUSTER RNAseq Study of healthy control cohort","description":"CLUSTER aims to discover novel disease mechanisms and biomarkers in children suffering from Juvenile idiopathic arthritis (JIA). Healthy controls were used as the control for baseline expression compared to children with JIA. The samples used in this study comes from blood samples that were collected from healthy volunteers recruited through Centre for Adolescent Rheumatology Versus Arthritis, spanning from children to adult age. These samples were then processed for PBMC isolation followed by sorting cells into 4 different immune cell types. All of these samples were then sequenced by NovaSeq6000,together with the JIA samples.\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001440","title":"Host-microbe interactions in a novel SARS-CoV-2 human challenge model","description":"This research leverages previously collected clinical data and samples from a first-in-human SARS-CoV-2 challenge study conducted in healthy adults without serological evidence of prior infection or vaccination. We performed shotgun metagenomic and RNA sequencing of serially collected mid-turbinate nasal and throat swab samples from 34 adults who were inoculated with a wild-type virus, 18 (53%) of whom developed PCR-confirmed infection. By integrating microbiome and host transcriptome data, this research will provide insight into the complex interplay between the upper respiratory microbiota and the host immune system, offering a deeper understanding of factors that influence susceptibility to and severity of SARS-CoV-2 and other respiratory viral infections.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[35361992],"external_links":null,"is_released":true,"released_date":"2026-04-02T13:24:24.227529+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001441","title":"Trio Exome Sequencing for epilepsy","description":"We performed trio exome sequencing for a family with seizures. Trio-based exome sequencing identified a candidate variant in PREX. Functional assays demonstrated that the detected variant reduced the GDP/GTP exchange activity of PREX1 for RAC1 and attenuated the RAC1-PAK1 signaling compared with wild-type PREX1. The deposited dataset consists of the joint-called filtered VCF (GRCh37/hg19) used in the manuscript. Access is controlled by a Data Access Committee in accordance with participant consent and IRB approval.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001442","title":"Study of wound response like states in glioblastoma","description":"In order to investigate wound reponse-like states in glioblastoma, we carried out experiments on primary tissue as well as organoids. Single cell RNA sequencing was performed on core and periphery of three human glioblastoma. Bulk RNA sequencing was performed on glioblastoma-derived organoids subject to treatment for 72h with plasma, hypoxia, or both, and analyzed at 0, 24, 72, and 144h.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-09T10:54:42.821275+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001443","title":"Paired DNA and RNA sequencing uncovers common and rare genomic variants regulating gene expression in the human retina","description":"In this study, we uncovered common and rare genomic variants shaping retinal expression profiles. This includes 1,483,595 significant cis-expression quantitative trait loci (eQTLs) impacting 9,959 and 3,699 genes in NSR and RPE, respectively, with associated genomic variants enriched to cis-candidate regulatory elements and notable shared eGenes between NSR and RPE. We also detected 1051 expression outliers and prioritised 299 rare non-coding single-nucleotide, structural variants or copy number variants as plausible drivers for 28% of outlier events. This study increases understanding of gene expression regulation in the human retina.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-07T12:38:19.507242+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001444","title":"Clinical data of liver cancer patients from EuCanImage - Use case 1 Synthetic","description":"This study is part of EuCanImage project. It contains the standardized clinical information following FHIR model. The data was collected together with MRI of patients diagnosed with liver cancer (HCC) and controls (non-HCC). All data is synthetic.","abstract":null,"study_type":"Synthetic Genomics","pubmed_ids":[],"external_links":[{"url": "https://xnat.bmia.nl/data/projects/euc_fcrb_uc1", "name": "EuroBioimaging", "label": "UC1 in EuroBioimaging"}],"is_released":true,"released_date":"2025-11-26T10:00:15.531539+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001445","title":"Profiling the genomic landscape and evolutionary history of polyploid giant cancer cells in undifferentiated pleomorphic sarcomas","description":"Polyploid giant cancer cells (PGCCs), characterised by multi-nucleation and atypical nuclear morphology, are a common feature of undifferentiated pleomorphic sarcomas. While PGCCs may be a critical substrate for cancer evolution, their formation pathways and the genomic consequences of PGCCs remain relatively under explored. \r\nIn this study, we characterise PGCCs in undifferentiated pleomorphic sarcomas, as well as their histological mimics, and use topographic single-cell DNA sequencing (scDNA-seq) to investigate their genomic landscape. We selected PGCCs based on their nuclear morphology, including mono-nucleated or multi-nucleated bizarre, misshapen nuclei and analysed them at single-cell resolution. Our findings highlight PGCCs as a highly heterogeneous and evolutionarily dynamic component of undifferentiated pleomorphic sarcomas.\r\n","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-10T18:20:20.242476+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001446","title":"Whole genome and tumor panel sequencing in a patient suspected of Muir-Torre syndrome","description":"This dataset includes whole genome sequencing of blood (1 sample) and targeted panel sequencing VCFs from seven tumor samples from a patient with Muir-Torre syndrome, a subtype of Lynch syndrome. WGS identified a deep intronic pathogenic MSH2 variant, and tumor sequencing revealed somatic MSH2 mutations confirming mismatch repair deficiency. The data highlight the value of WGS in detecting clinically significant non-coding variants missed by standard germline testing.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001447","title":"Single-nucleus profiling of postmortem diffuse midline gliomas identifies mitochondrial biogenesis as a resistance mechanism to imipridone therapy","description":"Diffuse midline glioma, H3 K27-altered (DMG), remains a lethal pediatric brain tumor with limited therapeutic options, and imipridone therapy produces only temporary responses before recurrence. To investigate resistance mechanisms, we performed single-nucleus RNA and chromatin accessibility profiling on 22 postmortem DMG specimens treated with imipridones and/or standard care, alongside functional assays of imipridone sensitivity and mitochondrial activity in DMG cell lines. Imipridone-treated tumors showed reduced mesenchymal transition, decreased myeloid-derived suppressor cells, and downregulation of aberrant enhancer activity associated with H3 K27 alterations. Mechanistically, treatment selected for increased mitochondrial density, turnover, and membrane potential. Together, these findings identify mitochondrial biogenesis as a key marker and driver of imipridone resistance, providing a rationale for combination strategies to improve therapeutic efficacy.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001448","title":"Evaluation Of The Role Of Tumor Mutational Burden As A Prognostic Biomarker In Follicular Lymphoma ","description":"In this study, we have evaluated TMB through a 409-gene panel in 135 patients with FL or transformed FL (tFL) at presentation. We analyzed the association of TMB with prognosis and specific genetic alterations recurrent in FL, with the goal of identifying molecular markers that could improve prognostic assessment. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001449","title":"Prevalence and association of microsatellite instability and Lynch syndrome Pan-Cancer and development of a personalized cancer risk prediction tool for Lynch syndrome carriers in India","description":"The study aimed to systematically study MSI/ MMRd status in tumour DNA and germline mutations in mismatch repair (MMR) genes across a unique, large and heterogeneous group of commonly observed non-colorectal  gastrointestinal and genitourinary tumours in the Indian population.  ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-09T10:52:26.647245+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001450","title":"A prospective multicenter study of plasma ctDNA versus archival tumor tissue to guide FGFR-targeted therapy in metastatic urothelial cancer - Targeted","description":"Targeted sequencing data related to the publication titled \"A prospective multicenter study of plasma ctDNA versus archival tumor tissue to guide FGFR-targeted therapy in metastatic urothelial cancer.\" FGFR alterations, seen in up to 25% of metastatic urothelial carcinoma, can be exploited with targeted therapy. Here, we perform targeted sequencing of cell-free DNA, archival FFPE, and white blood cell DNA to compare ctDNA versus tissue for FGFR biomarker status and monitor temporal changes to FGFR over the disease course, specifically after progressing on targeted therapy. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-24T11:09:30.036548+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001451","title":"Profiling the architecture of stage III colon cancer with spatial transcriptomics.","description":"Using 10X Genomics Visium, we profiled FFPE samples from 48 stage III colon cancer patients enrolled in the PETACC8 trial (Fédération Française de Cancérologie Digestive) to delineate multicellular ecosystems that are both histologically and molecularly informative.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001452","title":"Long read whole genome sequencing data from brain postmortem tissue","description":"Chart genetic variation in the human brain in healthy controls and Parkinson’s disease (PD) patients. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-07T12:13:08.907627+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001453","title":"Molecular profiling of HGBCL-DH-BCL2 patients treated in the HOVON-152 trial","description":"Using targeted sequencing and shallow whole genome sequencing for simultaneous screening of mutations, copy number alterations, and translocations, this study aims to identify genomic alterations associated with outcome in HGBCL-DH-BCL2 patients of the HOVON-152 trial.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-02T09:19:18.782448+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001454","title":"Transcriptomic profiling of proximal and distal regions of human long head biceps tendon","description":"Tendinopathy is a prevalent musculoskeletal disorder marked by extracellular matrix disorganization, collagen remodeling, vascular ingrowth, and pain, yet its underlying molecular mechanisms remain insufficiently defined. The long head of the biceps tendon (LHBT) is particularly prone to mechanical overload and early degenerative changes, making it a relevant model for studying tendon pathology. In this study, we aimed to characterize region-specific gene expression changes along the LHBT to better understand the molecular basis of degeneration. We collected paired proximal and distal LHBT tissue from patients undergoing rotator cuff repair surgery and performed bulk RNA sequencing. This approach enables the identification of degeneration-associated transcriptional signatures while minimizing inter-patient variability.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-05T10:07:54.010701+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001455","title":"Multiome analysis of local peritumoral glioblastoma cells ","description":"To extend our understanding and establish validated models of the local peritumoral Glioblastoma (GB) cells that remain in the patient after surgery, we have collected and explanted matched samples from the bulk tumor and the invasive edge beyond the 5-ALA fluorescent border of eleven GB patients. We performed whole exome sequencing and RNA sequencing along with multiomics profiling, combining single nucleus RNA-seq and ATAC-seq.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001456","title":"NAR-GAB  2025 deposit data","description":"Human exome gVCFs: rare-disease cohort for the NAR-GAB 2025 study on splicing-SNV prioritization.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-22T08:54:36.317607+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001457","title":"A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies","description":"Pineoblastoma is a clinically aggressive childhood brain tumor composed of distinct molecular subgroups with divergent driver genes, demographics, and clinical outcomes. To identify developmental origins and mechanisms governing disease pathogenesis, we derive single-cell transcriptomes from pineal parenchymal tumors, aligning malignant cells with our atlas of pineal gland development to retrace cellular origins. Integrative computational analyses maps pineoblastoma origins to transient cycling pinealocyte progenitors during development. Lineage-specific perturbation of suspected drivers in the early pineal gland yields preclinical models representative of consensus molecular subgroups. Multi-omic characterization of patient tumors and these models uncovers a tumor-associated photoreceptor signature common to pineoblastoma, retinoblastoma, and Group 3 medulloblastoma. Transcriptional activity of this signature within respective cellular origins establishes a developmental basis for molecular similarities between entities. Photoreceptor signature constituents are selective dependencies across these anatomically distinct central nervous system malignancies, motivating future studies evaluating developmentally encoded programs of malignancy as potential therapeutic liabilities.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-10T16:03:44.210051+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001458","title":"Single cell whole genome sequencing of 5 ovarian cancer specimens","description":"Single cell whole genome sequencing BAM files for five ovarian cancer specimens.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-08T14:22:33.504942+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001459","title":"Single-cell RNA sequencing of metastatic colorectal cancer patient-derived xenografts treated with cetuximab","description":"Single-cell RNA sequencing was performed on a cetuximab-sensitive metastatic colorectal cancer (mCRC) patient-derived xenograft (PDX) model. The objective of this analysis was to assess whether the transcriptional patterns identified in the single-cell RNA-seq data of matched organoids were preserved in the in vivo context. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-10T14:57:28.302683+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001460","title":"Single-cell RNA sequencing of metastatic colorectal cancer organoids treated with cetuximab","description":"Single-cell RNA sequencing was performed on metastatic colorectal cancer (mCRC) organoids derived from a cetuximab-sensitive patient-derived xenograft (PDX) model. The objective of this analysis was to investigate, at single-cell resolution, the transcriptional changes previously identified in bulk RNA-seq analyses of PDX models exposed to anti-EGFR therapeutic pressure. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-10T14:57:29.784941+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001461","title":"The Parent-of-Origin-Aware genomic analysis (POAga) study","description":"The Parent-of-Origin-Aware genomic analysis (POAga) study combines nanopore sequencing and strand-seq technologies to determine the parental segregation of high penetrant hereditary cancer conditions. Specifically, in this initiative, POAga is performed using blood derived from patients with Pancreatic Cancer, Hereditary Breast and Ovarian Cancer, Lynch syndrome, hereditary paraganglioma-pheochromocytoma syndrome and CDH1-related Diffuse Gastric and Lobular Breast Cancer Syndrome (DGLBCS).\r\nStrand-seq provides chromosome-scale but sparse phasing of single nucleotide variants (SNVs). Phased SNVs from strand-seq are then combined with nanopore long-reads to provide chromosome-scale phasing of nearly all the genomic variants. To assign parent-of-origin to H1 and H2, we then use DNA methylation data, which can be obtained from nanopore data, at known human imprinted regions. As we already know which allele is methylated (maternal or paternal) in these imprinted regions, we can assign a maternal or paternal origin to chromosome-scale haplotypes and genomic variants. This technology allows the assignment of parental segregation without parental data.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001462","title":"Bulk RNA-sequencing data of hiPSC-derived mDA neurons from (i) 3 control and 4 patient (SNCA) lines at 2 time points, 4 weeks and 6 weeks and (ii) 4 control lines – untreated, treated with insulin, and with insulin and exenatide.","description":"Neuronal insulin resistance is linked to the pathogenesis of Parkinson’s disease through unclear, but potentially targetable, mechanisms. We delineated neuronal and glial mechanisms of insulin resistance and glucagon-like 1 peptide (GLP-1) receptor agonism in human iPSC models of synucleinopathy, and corroborated our findings in patient samples from a Phase 2 trial of a GLP-1R agonist in Parkinson’s (NCT01971242).  Human iPSC models of synucleinopathy exhibit neuronal insulin resistance and dysfunctional insulin signalling, which is associated with inhibition of the neuroprotective Akt pathways, and increased expression of the MAPK-associated p38 and JNK stress pathways. Ultimately, this imbalance is associated with cellular stress, impaired proteostasis, accumulation of α-synuclein, and neuronal loss. The GLP-1R agonist exenatide led to restoration of insulin signalling, associated with restoration of Akt signalling and suppression of the MAPK pathways in neurons. GLP-1R agonism reverses the neuronal toxicity associated with the synucleinopathy, through reduction of oxidative stress, improved mitochondrial and lysosomal function, reduced aggregation of α-synuclein, and enhanced neuronal viability. GLP-1R agonism further suppresses synuclein induced inflammatory states in glia, leading to neuroprotection through non cell autonomous effects. In the exenatide-PD2 clinical trial, exenatide treatment was associated with clinical improvement in individuals with higher baseline MAPK expression (and thus insulin resistance). Exenatide treatment led to a reduction of α-synuclein aggregates, and a reduction in inflammatory cytokine IL-6. Taken together, our patient platform defines the mechanisms of GLP-1R action in neurons and astrocytes, identifies the population likely to benefit from GLP-1R agonism, and highlights the utility of GLP-1R agonism as a disease modifying strategy in synucleinopathies.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001463","title":"Cell-free DNA methylation profiling for non-invasive detection and classification of lymphoma","description":"Compared with traditional tissue biopsies used for lymphoma diagnosis, cell-free DNA methylation profiling offers a minimally invasive approach capable of capturing lymphoma-specific epigenetic alterations. This study investigates genome-wide methylation patterns in plasma using cell-free methylated DNA immunoprecipitation and sequencing (cfMeDIP-seq). Differential methylation analysis of discovery samples identified lymphoma-associated hypermethylated regions that were used to develop classification models for lymphoma detection. Validation analyses demonstrated high accuracy and strong associations between cfDNA methylation scores and independent measures of tumor burden and clinical outcome. These findings support cfDNA methylation profiling as a sensitive approach for non-invasive lymphoma diagnosis.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-15T10:14:43.590698+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001464","title":"Diagnostic utility of clinical genome reanalysis in rare pediatric disorders using long-read sequencing","description":"More than half of presumed genetic disease cases remain undiagnosed following exome and/or short-read genome sequencing (SR-GS). Long-read genome sequencing (LR-GS) has emerged as a promising next step for uncovering etiologies missed by current standard-of-care SR genetic testing. However, structural variant (SV) interpretation remains a major challenge in LR-GS clinical pipelines, owing to limitations in SV call reliability, population allele frequency estimation, and evaluation of functional impact. To further develop strategies for the effective clinical use of LR-GS, we performed LR-GS using PacBio HiFi technology on 20 families with developmental disorders of suspected genetic origin and prior negative or inconclusive genetic testing (including exome and/or genome sequencing). Analysis was performed using a comprehensive pipeline integrating phased assembly– and read-based variant calling with LR-GS population allele frequency filtering. Phenotype-driven variant prioritization using Human Phenotype Ontology (HPO) terms was performed using a combination of tertiary analysis solutions, including publicly (SvAnna) and commercially (Illumina Emedgene) available tools. Definitive diagnostic findings were identified in 1/20 (5%) families. Variants of suspicious diagnostic significance were identified in 6/20 (30%). All findings of diagnostic significance were clinically confirmed using the proband’s prior clinical SR sequencing results, demonstrating the value of reanalysis and highlighting differences in clinical interpretation. One case harbored a homozygous ~50 kb deletion of initial interest that was only detected with LR-GS; however, it was ruled inconclusive based on frequency data from LR-GS population databases, underscoring the necessity of population filtering for structural variant clinical interpretation. Collectively, the observed increase in diagnostic yield (by 35% including suspicious findings) in this exome-/SR-GS-negative clinical cohort was driven primarily by genome reanalysis rather than identification of variants unique to LR-GS data. Additional functional studies are necessary to elucidate the clinical relevance of suspicious findings.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-06T10:42:15.826416+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001465","title":"Single-cell RNA sequencing of human omental tissue in benign and metastatic ovarian cancer","description":"To elucidate the cellular and molecular mechanisms underlying omental homeostasis and its transformation during ovarian cancer metastasis, a human omental cell atlas was generated encompassing both benign and metastatic conditions. Single-cell RNA sequencing was performed on freshly dissociated omental tissue samples from patients with newly diagnosed benign and malignant disease. Samples collected during diagnostic surgery covered distinct anatomical regions, enabling comparison between non-metastasized omentum and sites along the metastatic gradient, including distant, peritumoral, and tumor core areas.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-16T16:28:22.861299+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001466","title":"Resolution and methylation patterns of supernumerary marker chromosomes","description":"Herein we study the structure of ring and marker chromosomes in 10 carriers. The aim is to gain understanding of the formation and function of ring and marker chromosomes.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-17T15:59:42.866039+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001467","title":"Molecular profiles in early onset prostate cancer","description":"Paired germline (blood) and tumour samples were collected from prostate cancer cases <65 years at diagnosis to identify genetic changes in early onset prostate cancer.  Whole exome sequencing was performed on these samples. The aim was to determine if these changes are associated with more aggressive disease and to identify targets for treatment and screening by identifying associations with family history, DNA repair germline mutations, and clinical features.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-10T11:00:50.542165+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001468","title":"B cell activation","description":"To investigate the gene programs involved in B cell activation and antibody switching, we profiled the gene expression at the single cell level as well as the antibody repertoire of human naive and memory B cells at resting and following three time points of activation. Through CRISPR perturbations, we defined IRF4 as a central regulator of both GC and plasma cell fates, acting independently of PRDM1 in GC commitment. Finally, leveraging machine learning classification methods trained solely on transcriptomic profiles, we accurately predicted sister cell relationships, revealing that plasma cell gene expression programs are heritable and tightly conserved within a clone. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-02T09:43:22.989225+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001469","title":"PTEN homozygous deletion is a negative prognostic factor in Tumor Treating Fields-treated glioblastoma, IDH wildtype patients","description":"This study investigates genomic determinants of outcome in glioblastoma, IDH-wildtype patients treated with Tumor Treating Fields (TTFields) in addition to standard radiochemotherapy. Tumor tissue from primary glioblastoma at initial diagnosis was profiled using the Illumina TruSight Oncology 500 (TSO500) targeted sequencing panel to characterise somatic alterations. The overarching goal is to provide exploration of genomic determinants of survival and treatment response in TTFields-treated glioblastoma, IDH-wildtype.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-07T12:37:24.640939+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001470","title":"Single cell RNAseq analysis of cultured human B cell","description":"We developed an optimized in vitro model that drives human naïve B cells into ASCs through a two-step culture on stromal feeders. In the first phase, B cells were activated on CD40L-expressing stromal cells with BAFF, IL-4, IL-21, and IL-2; in the second, they were transferred to MS5 fibroblasts with IL-6 to promote terminal differentiation confirmed by the generation of CD20loCD38hiCD138+ plasma cells.  To map transcriptional dynamics, we performed scRNA-seq at day 0 (D0), D6, D8, and D10, analyzing 17,220 cells that segregated into 12 clusters","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-17T17:36:00.608681+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001471","title":"In vitro depletion of Caveolin-1 in human plasmablast cells","description":"In humans, unlike in mice, Cav-1 is expressed not only after B-cell activation but also in PC progenitors, plasmablasts, and mature PCs. To assess its functional role during B-cell differentiation, we used our previously published in vitro B-cell differentiation model and transfected day-5 cells with CAV1-targeting siRNAs. This resulted in a significant reduction of both CAV1 mRNA and protein levels by day 7, compared with scrambled siRNA controls. Bulk RNA-seq was then performed on day-7 plasmablasts transfected with siRNA-CAV1 versus siRNA control to compare their transcriptomic profiles (n = 4 experiments).","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-17T17:35:28.315506+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001472","title":"Transcriptomic subgroups in soft tissue tumors correlate with morphologic subtype, genomic features, and outcome ","description":"We assessed gene expression (GGE) profiles and gene fusions as detected by transcriptome sequencing (RNA-seq) of 704 soft tissue tumors (STT) representing 56 different tumor types. Comparison with follow-up data identified transcriptional subclusters among sarcomas with complex genomes and among adipocytic tumors that correlated with metastasis-free survival and local recurrences, respectively. Thus, RNA-seq analysis of STT provides clinically important information. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-26T12:26:07.552486+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001473","title":"SF3B1 splicing signature","description":"We describe individuals with de novo pathogenic variants in SF3B1. SF3B1 is a core component of the U2 snRNP complex that ensures accurate branchpoint and 3′ splice-site recognition, and its mutations induce aberrant splicing that contributes to tumorigenesis, notably in myelodysplastic syndromes. We aim to study splicing defects associated with constitutional pathogenic variants.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-17T15:55:43.803429+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001474","title":"Spatial profiling of hepatocellular carcinoma identifies distinct tumor and immune micro-ecosystems related to patient outcomes","description":"Hepatocellular carcinoma (HCC) shows substantial intra-tumor heterogeneity that remains poorly understood. Using spatial transcriptomics, we identified 13 recurrent tumor and stromal micro-ecosystems (MES) and mapped their spatial organization and biological functions. One immune-enriched MES containing Kupffer cell–like macrophages was strongly associated with improved disease-free survival and response to atezolizumab–bevacizumab. Our findings demonstrate the value of spatial profiling for revealing rare but clinically meaningful cellular communities.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001475","title":"DCIS fresh frozen fragmentomics dataset","description":"Ductal carcinoma in situ (DCIS) is a non-obligate precursor lesion of breast cancer (BC). Often detected by mammography, most cases are managed through surgical and/or radiotherapy approaches. Today, it is not possible to predict which patients will progress to invasive disease. Here, we evaluated high-depth whole-genome sequenced (WGS) DCIS, enriched for highgrade clinical lesions, to understand whether deep WGS could reveal biological insights and/or personalized therapeutic vulnerabilities that may be targetable. We find genomic locations that are likely susceptible to producing the initiating lesion for structural variations (SVs) prone to subsequent evolution, termed SHOREs (Susceptibility HOtspots for Rearrangements and ongoing Evolution). We additionally highlight individualized therapeutic potential that would otherwise not be appreciable without WGS. We posit that holistic WGS profiling could offer a more precise stratification approach, discerning higher-risk cases for prospective clinical studies on personalized therapies, from truly low-risk cases suitable for active monitoring. To substantiate our WGS findings, we also performed RNAseq on the same samples, this EGA study contains the RNAseq data. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-27T11:32:37.396377+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001476","title":"Single-cell Kinnex sequencing of Alzheimer's disease isoform profile","description":"Alzheimer’s disease (AD) is the most common cause of dementia, yet its molecular causes remain incompletely understood. RNA diversity in part arising from dysregulated splicing may contribute to AD pathogenesis; however, the ability to interrogate the resulting full-length isoforms in single brain cells has been technologically limited. Here we report the use of PacBio Kinnex long-read sequencing combined with 10X Genomics single-cell preparations to identify both annotated and unannotated RNA isoforms. Eight AD and seven non-diseased post-mortem human brains yielded ~70,000 single nuclei showing diverse, differentially expressed, and switched transcripts in multiple genes. Cell-type-specific isoform expression and variants with intra-exonic junctions associated with reverse transcriptase-mediated somatic gene recombination were also detected. Novel isoforms, including CHI3L1 and SEPTIN4, were altered in AD. Kinnex sequencing of RNA isoforms from single nuclei detected vast isoform diversity amongst brain cell types, representing an under-explored element in AD and other brain disorders.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-19T16:34:40.35151+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001477","title":"BCAC TIIC Data","description":"Data on spatially-resolved tissue infiltrating immune cells (TIICs) from 17,265 breast cancer patients of European descent, from studies participating in the Breast Cancer Association Consortium, together with linked clinical data. ","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-15T17:16:51.991178+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001478","title":"NIBIT-EPI-MESO study samples","description":"Multi-omics analysis of pre-immuno checkpoint inhibitors (ICI) therapy lesions from 91 pleural mesothelioma (PM) patients enrolled in the multicenter NIBIT-EPI-MESO study.\r\nNeoplastic lesions were characterized using multiple molecular platforms, including RNA sequencing (n=82), Whole Exome Sequencing (WES) (n=87), Reduced Representation Bisulfite Sequencing (RRBS) (n=83) and cell-free methylated immunoprecipitation sequencing (cfMeDIP-seq) (n=18). Tumor samples were collected during the standard diagnostic pleuroscopy or thoracoscopy before ICI therapy. Matched Peripheral Blood Mononuclear Cells (PBMC) were collected from PM patients before ICI therapy.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-24T12:22:43.485356+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001479","title":"Multiple Myeloma treated with BCL2 inhibitor based treatment","description":"Whole Genome Sequencing from patients with multiple myeloma treated with BCL2 inhibitor based treatment. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-17T17:03:03.282386+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001480","title":"Genomic landscape of aplastic anemia","description":"This study investigates the genomic landscape of aplastic anemia using complementary sequencing approaches. Single-cell DNA and protein profiling were performed using the Mission Bio Tapestri platform to characterize clonal structure and immunophenotypic features. Long-read whole-genome sequencing (PacBio) and single-cell whole-genome sequencing (BioSkryb) were also generated to capture structural variants and genome-wide clonal architecture. Together, these datasets aim to elucidate mutational processes and clonal evolution underlying aplastic anemia.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001481","title":"Molecular investigation of BCC HHI-ICI combination therapy","description":"We collected skin biopsies and PBMCs of patients with advanced BCC who underwent HHI-ICI combination therapy. We analyzed the skin biopsies with STx and the PBMCs with scRNA-seq to characterize the response of the immune cells, tumor cells and the tumor microenvironment to this therapy. We were interested in immune activation upon HHI and how that synergises with subsequent ICI.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-22T16:19:21.725244+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001482","title":"Unraveling the Physiological Impact of ANGPTL8 Loss-of-Function Variants in Humans ","description":"Summary statistics and individual level data associated with PheWAS and phenotypic profiling of individuals with heterozygous loss of mutations in the gene ANGPTL8","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-02T15:43:35.095618+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001483","title":"Integrative multi-omics reveals CDK1-dependent regulation of human CD4⁺ T cell differentiation","description":"Human CD4⁺ T cell activation and differentiation are shaped by coordinated signaling, transcriptional, and chromatin remodeling processes. Here, we generated an integrative multi-omics dataset combining bulk RNA-seq, bulk ATAC-seq, phosphoproteomics, and single-cell RNA+ATAC multiome profiling across Th0, Th1, and induced Treg polarization states. We identified rapid phosphorylation-driven regulation of RNA-binding proteins that precedes chromatin accessibility changes and subsequent transcriptional activation of effector genes. CDK1 inhibition revealed a selective impairment of inflammatory Th1 programs while preserving regulatory features in iTregs. These datasets define a CDK1-dependent signaling-to-chromatin regulatory axis in human T cell differentiation.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001484","title":"WES sequencing of metastatic colorectal cancer patient-derived xenografts with known response to irinotecan.","description":"Chemotherapy is the standard-of-care treatment for metastatic colorectal cancer (mCRC) and benefits some patients, but what distinguishes responders from non-responders is unclear. In this study, we expand a pre-existing collection (https://doi.org/10.1158/2159-8290.CD-24-0556) of molecularly annotated patient-derived xenografts to uncover functional predictors of response to 5-FU and irinotecan combination therapy (FOLFIRI) in mCRC. We complemented previous mutational profiles with whole exome sequencing for 46 xenografts with known response to irinotecan.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-17T16:37:18.70357+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001485","title":"Bulk RNA sequencing of metastatic colorectal cancer patient-derived xenografts with known response to irinotecan","description":"Chemotherapy is the standard-of-care treatment for metastatic colorectal cancer (mCRC) and benefits some patients, but what distinguishes responders from non-responders is unclear. In this study, we expand a pre-existing collection (https://doi.org/10.1158/2159-8290.CD-24-0556) of molecularly annotated patient-derived xenografts to uncover functional predictors of response to 5-FU and irinotecan combination therapy (FOLFIRI) in mCRC. We complemented previous expression profiles with bulk RNAseq for 38 xenografts with known response to irinotecan.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-17T16:37:20.33841+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001486","title":"3D hiPSC-derived Vessels-on-Chip bulk RNA-seq ","description":"Bulk RNA sequencing was performed on RNA isolated from human induced pluripotent stem cell–derived endothelial cell vessels-on-chip (hiPSC-EC VoCs), including monocultures and coculture VoCs, under untreated and TNFα-stimulated conditions. In addition, bulk RNA-seq was conducted on hiPSC-derived mural cells cultured within collagen I lumens (hiPSC-mural cell VoC). To investigate transcriptomic responses to laminar shear stress, bulk RNA-seq was also performed on hiPSC-EC VoC and coculture VoCs with adherent hiPSC-derived monocytes exposed to either static conditions or laminar flow (2 dynes/cm²) for 6 hours. Bulk RNA-seq data were generated from three independent biological replicates.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001487","title":"3D hiPSC-derived Vessels-on-Chip single cell RNA-seq","description":"Single-cell RNA sequencing (scRNA-seq) was performed on TNFα-treated three-dimensional vessels-on-chip (3D VoC) cultures exposed to either static conditions or laminar shear flow (2 dynes/cm²) for 6 hours, to characterize cell type–specific transcriptional responses. scRNA-seq data were generated from three independent biological replicates.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001488","title":"Airway Metagenomes from People with Cystic Fibrosis in South Australia","description":"This study comprises 127 respiratory specimens (sputum and bronchoalveolar lavage fluid) collected from 64 individuals with cystic fibrosis receiving clinical care in South Australia. DNA was extracted and subjected to shotgun metagenomic sequencing using both MGI and Oxford Nanopore Technologies platforms. The dataset captures diverse clinical states, including stable periods, antimicrobial exposure, pulmonary exacerbations, and varying lung-function metrics. The study aims to characterise taxonomic and functional diversity, pathogen dynamics—including early detection of Pseudomonas aeruginosa—and the ecological structure of CF airway microbiomes.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-27T10:00:51.965834+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001489","title":"Whole genome sequencing of ATCWGS42","description":"WGS of patient ATCWGS42, a patient who responded to BRAF/MEK targeted therapy but relapsed. This folder includes multi-region sequencing from the patient.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-08T14:21:16.541144+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001490","title":"Whole exome sequencing of ATCWGS42 primary tumour and PDX","description":"Genomic DNA was isolated from snap-frozen tissue and subjected to whole genome sequencing at The Center for Applied Genomics (Hospital for Sick Children, Toronto, ON) or at Beijing Genomic Institute (BGI). High-coverage whole exome-sequencing was performed at GeneSeeq Inc. (Toronto, Ontario, Canada) using IDT xGen exome panel.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-08T14:21:16.541144+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001491","title":"snRNAseq of ATCWGS42","description":"We performed single nucleus RNA-sequencing (snRNA-seq) on two regions from ATCWGS42 (ATCWGS42_E and ATCWGS42_R).","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-08T14:21:13.68242+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001492","title":"Bulk RNA-sequencing of PDX models","description":"This project contains bulk RNA-seq of PDX models containing grafts of ATC tumours. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-08T14:21:10.796802+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001493","title":"Epigenetically poised hybrid-lineage states fuel gastric cancer plasticity","description":"Gastric tumors exhibit profound inter-patient and intra-patient epithelial heterogeneity, however regulatory pathways driving gastric cancer (GC) lineage plasticity remain poorly defined. Here, we establish a patient-derived gastric organoid resource spanning the continuum of gastric pathophysiology, integrating genomic, transcriptomic, and epigenomic profiles to map dynamic epithelial states. We identify a distinct tumor cell population co-expressing stomach and intestinal lineage programs (“Sto/Int” cells), displaying enrichment of revival cancer stem cell programs and activation of pathways associated with therapy resistance. Single-nucleus multiomic analyses reveal that Sto/Int cells reside in an epigenetically poised configuration characterized by increased chromatin accessibility, low motif activity, and promoter-centric regulation, distinct from lineage-committed or active stem states. Extrinsically, we show that TGF-β signaling promotes Sto/Int cellular emergence, increasing intra-organoid heterogeneity and chemoresistance. Supporting their in vivo relevance, multiplex IHC analyses of primary GCs confirm the presence of Sto/Int cells at sites of tumor invasion. Collectively, our study defines a previously under-appreciated hybrid epithelial state that links gastric lineage interconversion to an epigenetically poised stem-like mechanism, establishing cellular plasticity as a fundamental feature of GC biology.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001494","title":"Single-cell RNA sequencing of human placenta","description":"The placenta is the major organ of feto-maternal communication underlying a healthy pregnancy. Any dysregulation in the proper functioning of the placenta can lead to adverse birth outcomes such as preterm birth. We performed single-cell RNA sequencing of human placenta samples from India, consisting of placentae from both preterm and term-delivering women. From a country like India, with the highest rates of preterm birth, we, for the first time, characterized the cellular and molecular underpinnings of preterm birth, providing novel insights into gene expression programs and molecular signatures that can be further translated to improve maternal and neonatal health during pregnancy.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001495","title":"Multi-omics profiling of stromal and epithelial evolution in Barrett’s oesophagus","description":"Spatially resolved study of Barrett’s oesophagus progression integrating stromal Smart-3SEQ 3′ RNA-seq (laser-capture micro dissected stromal regions) with shallow whole-genome sequencing of adjacent epithelial cells or epithelium without matched stroma, to characterise transcriptomic and chromosomal alterations across non-progressor, pre-progressor and progressor cohorts.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001496","title":"Large deletion predisposes to familial melanoma","description":"Mutations in CDKN2A and CDK4 account for ~40% of multi-case melanoma families, with another ~10% attributable to BAP1 and genes associated with telomere maintenance. Thus, a substantial proportion of the genetic risk underlying familial melanoma remains unexplained.\r\n","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-18T11:13:13.334332+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001497","title":"Whole genome sequencing data of pediatric B-other subtype acute lymphoblastic leukemia","description":"For a long time, approximately 70% of childhood B-ALL cases could be classified routinely, and the remaining 30% were classified into the “B-other” group lacking\r\nthe known genetic features. However, more recently, new genomic tools have uncovered new subtypes among the B-other groups. Approximately 10% of B-ALL cases lack the recurrent genetic abnormalities, and are referred as \"B-other\". They are typically more heterogeneous than other subtypes of B-ALL, and their prognoses are more variable. In a more recent update of the B-ALL classification, 27 subtypes were identified (Arber et al., 2022). The identification of some of these subtypes is dependent on NGS methods, such as RNA sequencing, which are not routinely used in all clinical laboratories. For example, ETV6::RUNX1-like and DUX4-rearranged subtypes have been identified using RNA sequencing. For this study, subtype predictions for some of the cases is acquired from ALLIUM (Krali et al., NPJ Precis Oncol., 2023) and ALLCatchR (Beder et al., Blood, 2022) based on the RNA-seq profiles.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-09T16:58:51.778361+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001498","title":"WES of sorted B lineage cells from patients with plasma cell neoplasms","description":"Whole-exome sequencing (WES) was conducted on cell populations isolated from each patient—diagnosed with either multiple myeloma (MM) or light-chain amyloidosis (AL) —including CD34⁺ hematopoietic progenitors, B-cell precursors, mature B cells, normal plasma cells, and clonal plasma cells. In the control cohort of healthy adults, the same target cell populations were analyzed, with the exception of clonal plasma cells, which were absent.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-11T09:28:41.255324+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001499","title":"PROMETEO","description":"The SOLTI-1503 PROMETEO trial was a single-arm, preoperative, window-of-opportunity phase II study conducted at four sites in Spain between December 2018 and February 2022. It enrolled female patients with operable HER2-negative breast cancer (triple-negative or Luminal B-like) and residual disease after neoadjuvant chemotherapy. Tumor biopsies were collected at five time points (baseline, post-NAC screening, C2D1, C3D1, and surgery) for translational research. This dataset includes raw paired-end RNA sequencing data (~110M reads per library) generated from the 113 biopy samples, archived in FASTQ format.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-22T12:49:35.798759+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001500","title":"Drug Perturbation of Primary Lymphoma Patient Samples and RNA Sequencing","description":"This submission contains 3'-end-based shallow-depth RNA sequencing data from 108 patients with chronic lymphocytic leukemia and 8 patients with lymphoma. Each primary patient sample was treated in vitro with DMSO as a control and with up to ten small-molecule drugs (ibrutinib, duvelisib, everolimus, trametinib, nutlin-3a, I-BET762, MK2206, selinexor, compound 26, and a combination of ibrutinib and compound 26). The samples were sequenced after 48 hours. The total data set consists of 1476 RNA sequencing samples from 6 batches (pilot, batch 1, batch 1 replicate, batch 2, batch 3, batch 4).","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-07T11:42:31.040099+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001501","title":"CLUSTER Read-counts matrix of RNAseq Datasets of JIA in methotrexate cohort","description":"CLUSTER aims to discover novel disease mechanisms and biomarkers in children suffering from Juvenile idiopathic arthritis (JIA). Currently, little is known about the pathological disease mechanisms of JIA and there are no validated tools capable of predicting response or non-response to treatment. The study aims to identify biomarkers for treatment response using RNAseq technology. \r\nThe samples used in this study comes from blood samples that were collected prior to patients receiving methotrexate treatment (naive). These samples were then processed for PBMC isolation followed by sorting cells into 4 different immune cell types. All of these samples were then sequenced by NovaSeq6000.","abstract":null,"study_type":"RNASeq","pubmed_ids":[40681434],"external_links":null,"is_released":true,"released_date":"2026-01-07T12:58:23.880672+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001502","title":"Personalized Medicine Strategy for MPNSTs: Using Precision Oncology on PDOX Models to Inform Tumor Boards","description":"Background: Malignant peripheral nerve sheath tumors (MPNSTs) are a heterogeneous group of aggressive soft tissue sarcomas with poor prognosis. Currently there is a lack of effective treatments for MPNSTs. Here, we propose a personalized medicine approach that integrates a precision oncology strategy guided by MPNST genomic analysis, with a functional validation of treatment response in an orthotopic xenograft model (PDOX) derived from the same MPNST. \r\nMethods: Comprehensive whole genome sequencing analysis was performed in primary MPNSTs, relapses and (in one case) metastases, following disease progression in two independent individuals. Matched MPNST PDOX models were generated by orthotopically implanting tumor fragments near the sciatic nerve of immunodeficient mice. Candidate targeted combination therapies were prioritized based on genomic alterations and tested in vivo in the PDOX models.\r\nResults: The feasibility of the developed strategy is illustrated for two MPNST patients, one Neurofibromatosis type 1 (NF1) individual that developed two independent MPNSTs and another sporadic MPNST case with multiple metastatic relapses. Genomic analysis revealed a remarkable degree of genomic stability across primary MPNSTs and their successive relapses in each patient, and even metastases in one individual. While based on a small number of cases requiringing additional analyses, this finding aligns with previous evidence suggesting a fair genomic conservation throughout tumor evolution. This stability supports the identification of consistent therapeutic vulnerabilities throughout disease progression. Among the therapies tested, co-treatment of MEK inhibitor (MEKi) plus bromodomain inhibitor (BETi) elicited the highest antitumor activity, resulting in approximately 60% tumor volume reduction in the sporadic MPNST PDOX model, whose patient has been receiving this therapy for eight months with sustained remission.\r\nConclusions: This study demonstrates the feasibility and clinical utility of integrating genomic-driven precision oncology with PDOX-based functional testing for MPNSTs. This strategy may support molecular tumor boards (MTBs) in their treatment decisions. The observed genomic stability supports the use of longitudinal tumor profiling to guide treatment, and the success of MEKi+BETi highlights its potential as a combination therapy for MPNSTs. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-17T15:21:42.029462+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001503","title":"STimage: Robust and interpretable prediction of gene markers and cell types from spatial transcriptomics data","description":"Spatial transcriptomics (ST) links tissue morphology with gene expression values, opening new avenues for digital pathology. Deep learning models are used to predict gene expression or classify cell types directly from images, offering significant clinical potential but still requiring improvements in interpretability and robustness. We present STimage as a comprehensive suite of models to predict spatial gene expression and classify cell types directly from standard H\\&E images. STimage enhances robustness by estimating gene expression distributions and quantifying both data-driven (aleatoric) and model-based (epistemic) uncertainty using ensemble approach with foundation models. Interpretability is achieved through attribution analysis at single-cell resolution integrated with histopathological annotations, functional genes, and latent representations. We validated STimage across diverse datasets, demonstrating its performance across various platforms. STimage-predicted gene expression can stratify patient survival and predict drug response. By enabling molecular and cellular prediction from routine histology, STimage offers a powerful tool to advance digital pathology.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-07T13:15:18.53087+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001504","title":"CLUSTER RNAseq Study of Juvenile Idiopathic Arthritis patients in Paired cohort","description":"CLUSTER aims to discover novel disease mechanisms and biomarkers in children suffering from Juvenile idiopathic arthritis (JIA). Currently, little is known about the pathological disease mechanisms of JIA. The study aims to understand the mechanism behind JIA using RNAseq technology. The samples used in this study comes from paired blood and synovial samples that were collected prior to patients receiving joint injection. These samples were then processed for PBMC and SFMC isolation followed by sorting cells into 4 different immune cell types. All of these samples were then sequenced by NovaSeq6000.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001505","title":"IMMUcan Upstream SCCHN3 cohort","description":"The goal of IMMUcan is to understand how the immune system interacts with tumors and how therapeutic interventions influence this interaction. This cohort includes patients from the UPSTREAM trial, with squamous cell carcinoma of the head and neck (SCCHN) cancer which has spread (metastatic) or the tumour has come back after previous treatment (recurrent). Comprehensive profiling data are integrated with longitudinally collected clinical information. Cellular profiling of the same tumor samples was performed using multiplex immunofluorescence imaging, imaging mass cytometry, and H&E staining.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-07T13:08:22.895112+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001506","title":"Distinct genomic profiles and clinical outcomes in constitutional mismatch repair deficiency-associated high-grade gliomas: insights into mutational signatures and clonal evolution","description":"Constitutional mismatch repair deficiency (CMMRD) is a rare cancer-predisposition syndrome, yet the mutational processes and clonal evolution of CMMRD-associated high-grade gliomas (HGGs) remain incompletely understood. In this study, mutational signatures and tumor evolution were analyzed in 25 CMMRD-associated HGGs. Germline biallelic mutations were most frequently identified in MSH6 (56.0%), followed by PMS2 (36.0%) and MLH1 (8.0%). Affected patients showed very early disease onset (mean 5.8 years) and poor clinical outcomes, with a mean progression-free survival of 16 months.\r\n\r\nDistinct genomic and clinical differences were observed between MSH6- and PMS2-associated tumors. MSH6-deficient HGGs were enriched for SBS6, whereas PMS2-deficient tumors showed predominance of SBS21, and these mutational signatures were correlated with prognosis. Clonal evolution analyses revealed early involvement of POLE/POLD1 mutations and persistence of the founding clone at recurrence. Overall, the study highlights the importance of mutational signatures and clonal evolution in shaping tumor behavior and clinical outcomes in CMMRD-associated HGGs.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-07T11:39:26.774584+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001507","title":"Bulk-mRNA sequencing comparing hiPSC derived vascular cells from CADASIL patient lines","description":"CADASIL is a hereditary brain small vessel disease caused by pathogenic variants in the NOTCH3 gene and causes degenration of Vascular Smooth Muscle cells in the brain. We performed bulk-mRNA sequencing and transcriptomic analysis from hiPSC derived vascular cells (hiPSC;Endothelial Cells; Neural Crest Cells; Vascular Smooth Muscle Cells) comparing CADASIL patient lines and respective isogenic-controls. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-11T09:30:11.986687+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001508","title":"Genomic Data from Patients with Advanced Rare Cancers Treated with Pembrolizumab","description":"Rare cancers lack effective evidence-based treatments despite contributing substantially to cancer-related mortality. The goal of this study is to identify molecular biomarkers associated with response to pembrolizumab in patients with advanced rare cancers.This dataset includes genomic profiling generated from patients enrolled in an investigator-initiated phase II basket trial of pembrolizumab.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-02T10:29:36.376777+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001509","title":"Transcriptomic Data from Patients with Advanced Rare Cancers Treated with Pembrolizumab","description":"Rare cancers lack effective evidence-based treatments despite contributing substantially to cancer-related mortality. The goal of this study is to identify molecular biomarkers associated with response to pembrolizumab in patients with advanced rare cancers.This dataset includes transcriptomic profiling generated from patients enrolled in an investigator-initiated phase II basket trial of pembrolizumab.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-02T10:29:36.376777+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001510","title":"Circulating Tumor DNA analysis in Relapsed/Refractory Germ Cell Tumors Treated with Salvage High-Dose Chemotherapy - IGG-04 Study","description":"Shallow whole genome analysis of circulating tumor DNA detected in the plasma of Relapsed/Refractory germ cell tumors treated with high dose chemotherapy","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-07T16:09:49.8949+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001511","title":"Whole exome and RNA sequencing of High-grade B-cell lymphoma NOS, DLBCL, Burkitt, and Double/Triple hit lymphomas","description":"High-grade B-cell lymphoma, not otherwise specified (HGBCL, NOS), stands out among aggressive lymphomas for its relative lack of specific and objective diagnostic pathologic criteria and absence of a characteristic gene expression signature. To address this, we conducted a comprehensive transcriptomic and genomic analysis across aggressive B-cell lymphoma samples from the University of Miami and Jackson Memorial Hospital. Our results reveal the presence of distinct Burkitt-like and DLBCL-like subgroups within HGBCL, NOS.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001512","title":"Whole genome sequencing data of paediatric patients with BCR::ABL1 acute lymphoblastic leukemia","description":"The BCR::ABL1 fusion results from the t(9;22)(q34;11.2) translocation, also known as the Philadelphia chromosome. In children, BCR::ABL1-positive leukemia is rare, accounting for approximately 3% of cases. The BCR::ABL1 oncoprotein activates multiple signaling pathways that drive cell proliferation. Historically, this subtype was associated with an extremely poor prognosis; however, the incorporation of tyrosine kinase inhibitors into therapy has markedly improved outcomes, with overall survival now approaching 80% in pediatric patients. Relapse most commonly occurs through the emergence of clones harboring kinase domain mutations, yet 30–40% of relapses arise in the absence of such mutations, a phenomenon that remains poorly understood.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-07T12:52:55.370294+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001513","title":"Single-cell multidimensional profiling of tumor cell heterogeneity in supratentorial ependymomas","description":"Supratentorial ependymomas (ST-EPNs) are aggressive and treatment-resistant pediatric brain tumors that form along the human cortex, with suspected origin from radial glia cells. Although histologically similar, ST-EPNs are molecularly classified into six distinct subgroups, many of them remaining understudied. Here, we integrated molecular cell states and spatial architecture to resolve the cellular origins and aberrant differentiation trajectories of ST-EPNs at single-cell resolution. We show that, while all ST-EPNs display a unified origin from neuroepithelial cells, different subgroups harbor highly diverse cell states and differentiation potential associated with neural or ependymal differentiation. Spatial mapping uncovered a higher-order structural tumor organization driven by presence of the mesenchymal state, and refines classical histological features based on detailed molecular resolution. By benchmarking a morpho-molecular cell-state classification system in different disease models and human tumors, we identified four cellular subtypes defined by the architecture of neurite-like extensions that mediate either self-renewal or fast, saltatory invasive phenotypes reminiscent of neurons during neurodevelopment. Collectively, our study provides a comprehensive framework for the study of ST-EPN cellular states, and reveals biologically relevant tumor compartmentalization with potential clinical implication.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2025-12-29T10:52:48.80373+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001514","title":"ERDERA Diagnostic Research Workstream - WES reanalysis (distributed approach)","description":"The ERDERA Diagnostic Research Workstream – WES reanalysis (distributed approach) aims to improve diagnostic yield by systematically reanalyzing existing whole exome sequencing (WES) data from rare disease cases. The goal is to apply updated bioinformatics pipelines, novel variant interpretation tools, and the latest reference databases to detect clinically relevant variants that may have been missed in earlier analyses. By using a distributed approach across multiple expert groups, the project fosters collaborative interpretation and knowledge sharing to enhance diagnostic outcomes for patients.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-09T15:56:46.510514+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001515","title":"Multi-faceted metastasis decoding: clonal fitness, site pressure, and transcriptional modulation","description":"The dynamics of unique pressures that evolve metastasis fitness due to genetic and non-genetic components in relationship to primary versus metastatic site has remained difficult to decipher due to the highly complex and intertwined relationship of these features to the heterogeneous clonal structures within tumors. To simplify this problem, we generated serially passaged patient-derived xenografts (PDX) that developed reproducible metastasis and examined them for robust clonal selection using DLP+ single cell genome sequencing. This clonal composition analysis identified a simpler PDX model of metastases that displayed very high intra-PDX clonal competitive fitness, marked with dominant and differential clonal sweeps at metastatic and primary sites by different clones. Further testing this fitness using the different combinations of clones’ transplantation, re-confirmed this high clonal selectivity of a metastatically fit clone at metastatic sites compared to the primary site, hence revealing copy number aberration (CNA) clonal state dependent fixed metastasis fitness. Overall, by testing 9 PDX lines we found two lines with reproducible metastasis which identified a model that simplified the complexities of tumor evolution during metastasis and revealed the dominant role of favorable CNA clonal structure in fixating fitness.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-14T15:33:45.598627+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001516","title":"Genomic landscape of aplastic anemia","description":"This study investigates the genomic landscape of aplastic anemia using complementary sequencing approaches. Single-cell DNA and protein profiling were performed using the Mission Bio Tapestri platform to characterize clonal structure and immunophenotypic features. Long-read whole-genome sequencing (PacBio) and single-cell whole-genome sequencing (BioSkryb) were also generated to capture structural variants and genome-wide clonal architecture. Together, these datasets aim to elucidate mutational processes and clonal evolution underlying aplastic anemia.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-30T15:50:15.990709+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001517","title":"Raw human sequencing data for “Characterization of intestinal immune responses in generalized human and murine lipodystrophy”","description":"This dataset contains raw FASTQ files generated from peripheral blood and intestinal biopsy samples collected for the study “Characterization of intestinal immune responses in generalized human and murine lipodystrophy.” Peripheral blood sequencing was performed on samples from three healthy donors as controls and from a patient with acquired generalized lipodystrophy and Crohn’s disease (AGLCD) at two distinct timepoints. Intestinal biopsy–derived immune cells were sequenced from three individuals with Crohn’s disease as disease controls, as well as from the AGLCD patient (single timepoint). The data include paired-end FASTQ files derived from single-cell RNA sequencing and T-cell receptor repertoire profiling, enabling analyses of immune composition, transcriptional states, and clonal T-cell expansion. All data are controlled-access human genomic datasets and require appropriate authorization for secondary use.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-12T12:35:20.57562+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001518","title":"Single cell RNA sequencing of non-small cell lung cancer.","description":"We performed single-cell RNA sequencing (scRNA-seq) on 36 NSCLC samples derived from 36 patients, including LUAD, LASC and LUSC. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001519","title":"Whole exome sequencing(WES) of non-small cell lung cancer","description":"We performed whole exome sequencing (WES) on 36 NSCLC samples derived from 36 patients, including LUAD, LASC and LUSC.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001520","title":"single-cell TCR sequencing of non-small cell lung cancer","description":"We performed single-cell TCR sequencing (scTCR-seq) on 36 NSCLC samples derived from 36 patients, including LUAD, LASC and LUSC.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001521","title":"Bulk RNA sequencing of non-small cell lung cancer","description":"We performed bulk RNA sequencing (Bulk RNA-seq) on 36 NSCLC samples derived from 36 patients, including LUAD, LASC, and LUSC.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001522","title":"Single-cell RNA sequencing of 20 non-small cell lung cancer patients","description":"Single-cell RNA sequencing (scRNA-seq) was performed on 20 patients with non-small cell lung cancer (including LUAD and LUSC). This includes both 5' scRNA-seq data and 3' scRNA-seq data, along with normal tissue sample data for the corresponding patients.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001523","title":"single-cell TCR sequencing of non-small cell lung cancer","description":"This data represents single-cell TCR sequencing performed on 9 non-small cell lung cancer samples and 6 normal tissue samples.\r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001524","title":"Whole exome sequencing (WES) of 17 non-small cell lung cancer patients.","description":"Whole exome sequencing (WES) was performed on 17 patients with non-small cell lung cancer (including LUAD and LUSC). Data from normal tissue samples from these patients are also included.\r\n","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001525","title":"Whole Genome Sequencing of 35 Multi-Region Colorectal Peritoneal Metastases Tumour Samples and 9 Matched Normal Blood Samples","description":"This dataset contains whole genome sequencing (WGS) data derived from 35 tumour samples and 9 matched normal blood samples collected from 9 patients with colorectal peritoneal metastases (CRPM). The tumour specimens were sampled from multiple spatial regions within each tumour to investigate intra-tumour heterogeneity. Sequencing was performed using the NovaSeq 6000 platform, with paired-end read lengths of 2×101 bp or 2×151 bp. These data were generated to study somatic mutations, structural variants, copy number alterations, mutational signatures, and clonal evolutionary trajectories associated with CRPM progression.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001526","title":"Pioneer factor-enabled chromatin compartments support prognostic gene expression programs in cohesin-destabilised lung cancer","description":"Loss of the cohesin subunit STAG2 is common in human cancers, yet how cohesin destabilisation reshapes enhancer activity and transcriptional identity remains unclear. Here we show that STAG2 loss in lung adenocarcinoma enables a pioneer factor-driven mode of enhancer-promoter communication that operates independently of canonical cohesin loops. Upon cohesin destabilisation, the pioneer factor FOXA2 engages previously primed enhancers, assembles an EP300-dependent cofactor complex, and establishes short-range, cohesin-devoid enhancer-promoter contacts that activate secretory-lineage gene programmes. These FOXA2-anchored “mini-loop” compartments drive transcriptional reprogramming associated with poor clinical outcome. Chromatin profiling and capture microC demonstrate that these de novo interactions form outside cohesin-occupied regions, depend on FOXA2 and its cofactors, and are functionally required for gene activation. Together, our findings indicate that cohesin destabilisation through STAG2 loss selectively reprogrammes chromatin architecture, permitting pioneer factor-supported regulatory rewiring that underpins cancer cell identity and prognostic gene expression.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001527","title":"Distinct functions of PBRM1 and BAP1 reconcile the course of kidney cancer evolution and disease progression","description":"Genomic profiling of ccRCC preclinical models using a targeted panel sequencing approach.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001528","title":"Liquid biopsy sequencing","description":"Liquid biopsy samples were collected from patients. Cell free DNA was extracted and profiled by NGS. Samples were analyzed by low pass whole genome sequencing, targeted panel sequencing using a custom hybrid capture panel, or both. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001529","title":"A benchmark of DNA methylation deconvolution methods for tumoral fraction estimation using DecoNFlow","description":"In cancer patients, circulating cell-free DNA (cfDNA) originates from both healthy and cancer cells, and the proportion of tumor-derived cfDNA serves as a surrogate marker of tumor burden. Tumoral cfDNA can be identified using patient-specific mutations or more general tumor-specific DNA methylation patterns that are preserved in cfDNA, enabling non-invasive cancer detection and monitoring. Accurately estimating tumor fractions remains challenging due to the heterogeneous mixture of cfDNA sources in body fluids. Computational DNA methylation deconvolution methods can address this by estimating tumoral fraction with or without reference methylomes. Here, we benchmarked 10 reference-based and 2 reference-free DNAm deconvolution tools and provide the data generated for this benchmarking, consisting of 10 neuroblastoma cell lines and one healthy cfDNA sample (pooled from 15 healthy cfDNA samples), profiled using cfRRBS.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-20T19:14:02.750221+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001530","title":"Longitudinal profiling of circulating tumor DNA across Phase II/III Ewing Sarcoma Trials","description":"Ewing sarcoma is an aggressive pediatric bone cancer characterized by FET-ETS translocations, with few additional alterations, most commonly affecting STAG2, TP53, and CDKN2A, and copy number variations. This study is based on a cohort of 222 patients with Ewing sarcoma, comprising 818 plasma, tumor, and bone marrow samples, profiled using custom targeted- and shallow whole-genome-sequencing to provide a comprehensive molecular characterization of ctDNA and tumor genomes across rigorously curated clinical trial cohorts and demonstrate the value of ctDNA profiling for molecularly informed risk stratification in Ewing sarcoma.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001531","title":"Single cell transcriptome and TCR sequencing of EBNA1, ANO2 and CRYAB-reactive T cells in multiple sclerosis.","description":"Molecular mimicry between Epstein-Barr virus (EBV) and self antigens in the brain has been suggested as a mechanism for how adaptive immune responses to EBV may contribute to multiple sclerosis (MS) disease pathogenesis. Anoctamin-2 (ANO2) and ɑ-crystallin B (CRYAB) have been identified as having homologous peptide sequences with the EBV antigen EBNA1. \r\nTo explore T cell cross-reactivity, we stimulated PBMC from four natalizumab-treated persons with MS with full-length bead-coupled antigens and sorted proliferating CD4+ T cells by flow cytometry after 8 days. Single cell RNA sequencing was performed on T cells reacting to EBV EBNA1, ANO2, CRYAB, albumin binding domain (ABD, irrelevant protein control) and anti-CD3.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-21T17:14:25.41959+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001532","title":"Emergence of oncofetal plasticity is ubiquitous in early colorectal cancers","description":"Metastasis formation is classically considered a late-stage event in colorectal cancer (CRC) evolution. Yet, the time and patterning by which metastatic competence is acquired remain poorly understood. Here, we show that metastasis-associated oncofetal cell states already emerge at the earliest stages of CRC, concurrent with invasive front formation. However, while necessary for metastasis, we detect them ubiquitously among early non-metastatic cancers, highlighting additional bottlenecks like immune evasion. To understand how oncofetal cells first emerge, we generated multiregional organoid models that reflect successive tumor progression stages within individual early-stage CRCs. Whole-genome sequencing and growth factor-dependency assays exclude tumor cell-intrinsic acquired traits. In contrast, single-cell spatial atlases of the tumor-microenvironment before and after malignant transformation revealed stereotypic patterning of fibroblast subtypes resembling normal tissue architecture, resulting in distinct regional microenvironments. At the onset of malignant growth into the submucosa, the first cancer-associated fibroblasts (CAFs) to appear strongly resemble submucosal trophocytes and colocalize with oncofetal cell states at invasive fronts. Functionally, fibroblast-organoid co-cultures confirm that these trophocyte-like CAFs induce plastic transitioning to oncofetal states. Thus, interactions between tumor and submucosal fibroblasts directly following malignant transformation dictate the timing and location at which oncofetal plasticity first occurs during CRC progression.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-20T19:16:43.460776+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001533","title":"IMMUcan SCCHN1 cohort","description":"The goal of IMMUcan is to understand how the immune system interacts with tumors and how therapeutic interventions influence this interaction. This cohort includes patients with confirmed locally recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) who receive first-line treatment with immune checkpoint inhibitors (ICI) or ICI combined with chemotherapy. Comprehensive profiling data are integrated with longitudinally collected clinical information. Cellular profiling of the same tumor samples was performed using multiplex immunofluorescence imaging, imaging mass cytometry, and H&E staining.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-10T16:01:21.541059+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001534","title":"Bulk RNA-seq of copy-number-defined clones from triple-negative breast cancer PDX primary tumours and metastases","description":"The dynamics of metastatic fitness reflect intertwined genetic and non-genetic influences that can differ between primary and metastatic sites, but these relationships are difficult to resolve in human tumours due to extensive intratumour heterogeneity. To simplify this problem, we generated serially passaged triple-negative breast cancer patient-derived xenografts (PDXs) with reproducible spontaneous metastasis and assessed clonal selection using DLP+ single-cell genome sequencing. Across nine PDX lines, two showed consistent metastatic outgrowth and strong, site-specific clonal sweeps consistent with copy-number aberration (CNA)–associated fitness differences. This EGA study contains only the bulk RNA sequencing (RNA-seq) data generated from PDX primary tumours and matched spontaneous metastases. Related DLP+ single-cell whole-genome sequencing (scWGS) data. are provided separately as an additional EGA study.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001535","title":"Urine cfDNA workflow for epigenomic profiling.","description":"Urine cell-free DNA (cfDNA) holds great promise as a non-invasive biomarker for diagnosis, prognosis and treatment monitoring of diseases. However, its clinical utility is challenged by high nuclease activity and rapid degradation, necessitating an optimized urine cfDNA workflow.\r\nWe evaluated a workflow for urine cfDNA methylation and fragmentation profiling, comparing PAXgene Urine Technology, with Streck Urine Preserve and unstabilized urine, using enzymatic methyl sequencing of cfDNA from healthy individuals, across multiple urine storage time points (immediate, 6 h, and 72 h). \r\nUrine stabilization significantly improved cfDNA yield and preserved cfDNA fragment sizes, while unstabilized samples exhibited marked degradation and reduced sequencing quality. \r\nMethylation analysis revealed high concordance between stabilized samples, with subtle divergence after 72 h. In contrast, unstabilized samples showed widespread methylation changes. Biological patterns were retained in stabilized urine cfDNA.\r\nOur study underscores the importance of well-designed (pre)analytical urine workflows to allow urine cfDNA (epi)genomic analyses.\r\n","abstract":null,"study_type":"Epigenetics","pubmed_ids":[42380575],"external_links":null,"is_released":true,"released_date":"2026-07-07T15:47:19.315882+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001536","title":"Investigating transcriptional changes in rapidly differentiated iPSC-derived neurons (i3Ns) harbouring the SNCA A53T mutation +/- RSL3","description":"In this study we performed bulk RNA sequencing of a iPSC-derived rapid neuronal model harbouring the Parkinson's disease associated A53T mutation in SNCA. These neurons were subsequently treated with a low dose of RSL3 (300nM) for 6 hours to establish the transcriptional impact of ferroptosis induction in the presence or absence of SNCA A53T mutation.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-12T15:36:22.288774+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001537","title":"Hybrid untargeted and targeted RNA sequencing facilitates genotype-phenotype associations at single-cell resolution","description":"Raw sequencing data for the manuscript \"Hybrid untargeted and targeted RNA sequencing facilitates genotype-phenotype associations at single-cell resolution\". It includes PacBio long-read scRNA-seq, illumina short-read scRNA-seq and Twist-based targeted scRNA-seq datasets for two adrenal samples. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-27T11:16:58.627033+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001538","title":"EstMB cohort participants sequenced with MGISEQ-2000 platform","description":"Ensuring the comparability of data generated across different sequencing platforms has become a pressing concern in efforts to uncover robust links between the microbiome and human health. In this study, we conducted a comprehensive comparison of taxonomic and functional profiles from matched human gut microbiome sample pairs, sequenced using both the MGISEQ-2000 (MGI) and NovaSeq 6000 (Illumina NovaSeq) platforms.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-24T12:34:17.064591+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001539","title":"cell-free Methylated DNA by Immunoprecipitation and Sequencing (cfMeDIP) of human meningioma samples.","description":"Raw data for cell-free Methylated DNA by Immunoprecipitation and Sequencing (cfMeDIP) of human meningioma samples.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-21T18:23:38.374711+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001540","title":"Transcriptomic insights into IPMN-associated PDAC progression","description":"This study investigates the transcriptomic heterogeneity and evolutionary progression of intraductal papillary mucinous neoplasms (IPMNs) and their associated pancreatic ductal adenocarcinomas (PDAC). Multi-region tumour sampling was performed to characterise spatial variation in gene expression and to identify transcriptional changes associated with malignant transformation. The project aims to improve understanding of tumour evolution in pancreatic cancer and to identify molecular pathways involved in IPMN-to-PDAC progression.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-10T13:57:51.135922+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001541","title":"Benchmarking V(D)J Repertoire Reconstruction: Bulk RNA-Seq vs PCR-Based RepSeq Validated by SMRT Sequencing","description":"The aim of this study is to benchmark methods for immunoglobulin repertoire profiling using human B-cell samples. We compare targeted VDJ mRNA sequencing and repertoire reconstruction from bulk RNA-seq data to PCR-independent full-length transcript sequencing using Single-Molecule Real-Time technology. The objective is to assess methodological biases and establish a robust reference framework for immunoglobulin repertoire analysis.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-21T10:58:15.26306+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001542","title":"PDAC organoids treated with LGK974","description":"Transcriptomic data from pancreatic ductal adenocarcinoma (PDAC) organoids to investigate the role of WNT7B. \r\n\r\nThis dataset includes:\r\n- Bulk mRNA sequencing of LGK974 treated pancreatic ductal adenocarcinoma (PDAC) organoids from three different patients for 24h","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-27T11:00:31.515796+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001543","title":"WNT7B-reporter organoids sorted","description":"Transcriptomic data from pancreatic ductal adenocarcinoma (PDAC) organoids to investigate the role of WNT7B. \r\n\r\nThis dataset includes:\r\n- Bulk mRNA sequencing of WNT7B-reporter pancreatic ductal adenocarcinoma (PDAC) organoids sorted for cells displaying low, medium and high expression of the reporter","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-27T11:00:28.205921+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001544","title":"Single cell RNAseq of PDAC organoids","description":"To study the role of WNT7B, three organoid lines were sequenced using SORT-Seq","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-27T11:00:34.75941+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001545","title":"Bleomycin Induced Pneumonitis cohort of the Exceptional Responders Program of the Garvan Institute of Medical Research","description":"Bleomycin is a cytotoxic antibiotic and forms a key component of the curative-intent chemotherapy regimens for germ cell tumours (GCT) and lymphoma. However, the drug can be associated with a range of lung toxicity, including idiosyncratic inflammation termed bleomycin induced pneumonitis (BIP), which can lead to irreversible interstitial fibrosis and death. This study aims to identify germline genomic changes associated with BIP in patients receiving bleomycin as treatment for GCT or lymphoma, who develop clinically significant BIP despite low predicted risk based on absence of traditional risk factors. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-27T14:12:33.321477+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001546","title":"WES Analysis of precancerous lesions in Lynch Syndrome","description":"The project focuses on identifying the genetic alterations involved in the early stages of tumor development in individuals with Lynch Syndrome. Using Whole Exome Sequencing (WES), the study aims to characterize somatic mutations and molecular pathways that drive the transformation from normal tissue to precancerous lesions. This research contributes to a better understanding of tumorigenesis in hereditary colorectal cancer syndromes.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-09T15:23:27.893667+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001547","title":"Müller Cell–Driven Induced Neurogenesis in the Adult Human Retina. Magda et al.","description":"Adult mammalian retinas usually can’t regenerate, so degeneration leads to permanent vision loss. Although species like zebrafish can replace retinal neurons using Müller glia, this was long thought impossible in humans. This work shows that in long-term cultures of adult post-mortem human retina, Müller glia can be induced—using soluble cues like FGF-2—to re-enter the cell cycle and generate neuron-like progeny without viral gene delivery. Importantly, some of these new cells display neuronal differentiation markers and express gene signatures consistent with multiple mature retinal neuron types, including rods and cones, bipolar cells, ganglion cells, amacrine cells, and horizontal cells. We sequenced the RNA of 17 human organotypic retina cultures from 3 different donors.\r\nManuscript is under review.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001548","title":"Transcriptomic profiling of skin biopsies from psoriasis patients following treatment with Zasocitinib","description":"The objective of this study is the exploratory analysis and characterization of psoriasis using RNA-seq-based profiling. Specifically, the cutaneous and serum biomarker profiles associated with the molecular, histological and clinical effects of Zasocitinib treatment in patients with moderate-to-severe plaque psoriasis were characterized. To evaluate differences between the transcriptomic profiles of Zasocitinib- and placebo-treated patients, exploratory biomarker endpoints included quantification of skin biomarkers, such as immune cell infiltration and mRNA expression levels in lesional and non-lesional skin, as well as quantification of circulating cytokines and other inflammatory biomarkers. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-23T15:39:30.081711+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001549","title":"Transcriptomic profiling of Hedgehog-high and Hedgehog-low HPV-negative HNSCC","description":"This study investigates transcriptomic differences between Hedgehog-high and Hedgehog-low HPV-negative head and neck squamous cell carcinoma (HNSCC). Tumors were stratified based on pathway-level genomic alteration scores and imaging-associated Hedgehog activity. RNA sequencing was performed on archival FFPE tumor samples to assess pathway activation and transcriptional programs associated with Hedgehog signaling. The dataset supports integrative radiogenomic and functional analyses of tumor-intrinsic signaling pathways.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001550","title":"Whole-exome sequencing of HPV-negative HNSCC to identify pathway alterations","description":"This study applies whole-exome sequencing (WES) to characterize genomic alterations in HPV-negative head and neck squamous cell carcinoma. Tumors were analyzed to derive pathway-level alteration scores, enabling stratification into Hedgehog-high and Hedgehog-low groups. The genomic data were integrated with imaging, transcriptomic, and functional analyses to investigate tumor-intrinsic Hedgehog signaling. The study aims to identify molecular features associated with biologically distinct tumor subgroups.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001551","title":"Iso-Seq enables discovery of novel isoform variants in human retina at single cell resolution","description":"We utilized Iso-Seq with full-length sequencing to profile the human retina at single cell resolution for isoform discovery. We generated a retina transcriptome dataset consisting of 25,302 nuclei from three donor retina, and identified 73,166 known isoforms and 27,880 novel isoforms across 10 major cell types.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-16T10:53:15.320712+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001552","title":"Measurable residual disease dynamics predicts progression and reveals a vulnerable state for immunotherapy interception in multiple myeloma","description":"The underlying dynamics of measurable residual disease (MRD) resistance in multiple myeloma (MM) remain insufficiently characterized. Addressing this gap could help in the design of tailored strategies empowered to eradicate MRD before relapse, which could increase the chances of long-term survival. In this study we characterized the genomic traits of MRD resistance in MM patients. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001553","title":"Characterizing the Landscape of Somatic Variants in Sorted Circulating Cell Subsets of Individuals with Systemic Lupus Erythematosus","description":"This study examined the landscape of somatic variants in circulating B cells of systemic lupus erythematosus (SLE) patients. Whole exome sequencing (WES) was performed on three distinct B cell subsets in addition to two hematopoietic controls: naïve (CD19+IgD+) B cells, memory (CD19+CD27+) B cells, double-negative (DN: CD19+IgD-CD27-) B cells, CD34+ cells, and CD14+ cells, obtained from peripheral blood of 35 adult SLE patients using fluorescence-activated cell sorting (FACS).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001554","title":"Liquid biopsy-based minimal residual disease monitoring  for early risk stratification and decision-making  in advanced non-small cell lung cancer","description":"Circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) monitoring shows promise for risk stratification and decision-making in cancer patients. However, factors like background noise from non-tumor DNA, clonal haematopoiesis, and non-shedding tumors may complicate manual interpretation and limit its clinical application. In this proof-of-concept study in advanced non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), we developed an algorithm that automatically classifies serial cell-free DNA (cfDNA) samples, thereby enabling reliable and reproducible interpretation, and preventing time-consuming manual interpretation in approximately 75% of patients. Importantly, application of the algorithm allowed early risk stratification and decision-making, specifically identifying approximately 35% of patients with short-term clinical benefit and approximately 25% of patients who may potentially benefit from treatment escalation. Simultaneous serum tumor marker (STM) monitoring further improved risk stratification and decision-making in our study, enabling accurate identification of all patients with a clinical benefit of at least one year. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-05T16:09:37.613192+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001555","title":"MLL1 Amplification Defines an Epigenetically Distinct and Targetable Subtype of TP53-Deficient AML","description":"Oxford Nanopore long-read sequencing was performed to profile genomic variation and 5mC/5hmC in the UoC-M1 cell line and bone marrow biopsy/aspirate samples from patients with TP53-mutant or MLL1-amplified AML.\r\n\r\nHigh-molecular-weight DNA was sequenced on R10.4.1 flow cells (FLO-PRO114, ONT) using a PromethION for up to 144 h. Samples were reloaded when pore activity decreased to 10%, and multiple runs were pooled as needed, generating 15–154 Gb (5–49× coverage) per sample. Basecalling and modified-base detection were performed with Dorado using the dna_r10.4.1_e8.2_400bps_hac model and its 5mCG/5hmCG model. Reads were aligned to the T2T-CHM13 (hs1) human reference genome using minimap2, and per-CpG modification calls were extracted with modkit. Structural variants, somatic SNVs/indels, and copy-number alterations were identified using Sniffles2, ClairS-TO, and QDNAseq, respectively. Differential methylation was analysed using methylKit.\r\n\r\nEnzymatic methyl-sequencing (EM-seq) was performed to map 5mC in bone marrow biopsy/aspirate samples from patients with TP53-mutant, MLL1-amplified, or MLL-rearranged AML.\r\n\r\nGenomic DNA libraries were prepared using the NEBNext Enzymatic Methyl-seq Kit (NEB) with unique dual indexes and sequenced as 150-bp paired-end reads on an Illumina NovaSeq X, generating approximately 16–25× raw genome coverage per library (10–16× after deduplication). Reads were processed using the nf-core/methylseq pipeline in EM-seq mode, including adapter and end trimming with Trim Galore, alignment to the T2T-CHM13 (hs1) human reference genome with Bismark/Bowtie2, duplicate removal, and per-CpG methylation extraction. No spike-in control was included; conversion efficiency was estimated from non-CpG (CHG/CHH) methylation and exceeded 98% in all libraries. Strand-merged CpG calls were used for downstream analyses.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001556","title":"Spatial transcriptomics of human meningioma samples.","description":"We performed spatial transcriptomic profiling of human meningioma samples to map gene expression patterns within their native tissue architecture.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-21T18:23:40.247852+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001557","title":"Exome Profiling of IDH-Mutant Glioma Treated With Combined PARP and Immune Checkpoint Inhibition: A Phase II Trial.","description":"This study profiles the tumor exome in IDH-mutant glioma treated with combined PARP inhibition and immune checkpoint blockade. Integration of the plasma methylome with matched tumor transcriptomics and DNA methylation.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001558","title":"IMMUcan Lung NSCLC2 cohort","description":"The goal of IMMUcan is to understand how the immune system interacts with tumors and how therapeutic interventions influence this interaction. This cohort includes patients with non-small cell lung cancer who had surgical resection. This is a subcohort of the EORTC SPECTAlung study. Comprehensive profiling data are integrated with longitudinally collected clinical information. Cellular profiling of the same tumor samples was performed using multiplex immunofluorescence imaging, imaging mass cytometry, and H&E staining.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-10T14:00:13.448616+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001559","title":"High-depth whole genome sequencing of 26 premalignant breast lesions","description":"Ductal carcinoma in situ (DCIS) is a non-obligate precursor lesion of breast cancer, representing 20-25% of newly diagnosed breast cancer lesions. It is currently not possible to predict which DCIS patients will progress to invasive breast cancer. The samples deposited here are part of a larger study using high-depth whole-genome sequencing (WGS) to investigate the somatic mutation genomic landscape of DCIS. Comprehensive evaluation of DCIS genomes aims to uncover biological insights into breast cancer progression and potential opportunities to stratify DCIS patients for personalised treatment options or active surveillance. Due to specific restrictions imposed by the ethical approval at sample collection, the use of the germline data is restricted to filtering of somatic mutation calls only and cannot be used outside this purpose.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-27T12:14:24.458658+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001560","title":"A mathematical model of cell-free DNA fragment size reveals cancer-specific fragmentomic patterns","description":"This study aim to test a mathematical model of cfDNA length distribution across multiple biodiy flulids. It try to investigate biological mechanisms of cfDNA fragmentation and release.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-06T11:05:00.750582+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001561","title":"Chromosomal instability shapes the tumor microenvironment of oesophageal adenocarcinoma via a cGAS–chemokine–myeloid axis","description":"This study employed whole-genome sequencing (WGS) to investigate genomic alterations in oesophagogastric adenocarcinoma, with a focus on mechanisms of chromosomal instability. Twelve tumour samples were analysed, including specimens obtained prior to neoadjuvant chemotherapy and at surgical resection. WGS was used to identify structural variants, quantify tumour mutational burden, and detect potential driver mutations across samples. The study aimed to correlate genomic measures of chromosomal instability with clinicopathological features to improve understanding of tumour biology.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-23T15:49:33.024914+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001562","title":"Single-nucleus transcriptome sequencing of the human motor cortex","description":"Single-nucleus RNA-sequencing of the human motor cortex in patients with ALS, C9ORF72-ALS-FTD, ALS-FTD and unaffected controls. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-30T16:38:17.949975+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001563","title":"Single-nucleus ATAC sequencing of the human motor cortex","description":"Single-nucleus ATAC-sequencing of the human motor cortex in patients with ALS, C9ORF72-ALS-FTD, ALS-FTD and unaffected controls. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-30T16:38:17.949975+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001564","title":"Diverse Cellular Composition in Alveolar Rhabdomyosarcoma  Revealed by Single Cell RNA Sequencing","description":"Using single cell RNAseq data to characterize tumor composition and cellular states for Alveolar Rhabdomyosarcoma. We find that that ARMS tumors harbor phenotypically and transcriptionally distinct malignant subpopulations within an immune-influenced microenvironment.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-18T09:26:19.108052+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001565","title":"Biallelic variants in the non-protein coding minor spliceosome components RNU6ATAC and RNU6ATAC cause syndromic monogenic autoimmune diabetes","description":"Non-protein coding genes are emerging as critical contributors to the aetiology of rare diseases, providing key insights into human biology and uncovering novel disease mechanisms. We identified 7 individuals from 4 families with early-onset diabetes (diagnosed <5 years) and immune dysregulatory features caused by biallelic variants in RNU6ATAC. RNU6ATAC encodes a small nuclear RNA (snRNA) acting as a catalytic component of the minor spliceosome, a protein-RNA complex mediating splicing of ~700 genes containing U12/minor-type introns. Variant screening of the other 64 minor spliceosome genes in 276 infants with diabetes identified 12 unrelated individuals with biallelic disease-causing variants in RNU4ATAC. Biallelic pathogenic RNU4ATAC variants are known to cause a variable spectrum of clinical features, which until now did not include diabetes. Clinically, 12/19 RNU6ATAC/RNU4ATAC patients had additional immune dysregulatory features, and 50% of patients tested were islet-autoantibody positive, strongly supporting an autoimmune aetiology for their diabetes. RNA-seq in 3 individuals with biallelic RNU6ATAC variants showed a pattern of intron retention in U12 intron-containing genes similar to that seen in RNU4ATAC-individuals (n=3), supporting a shared disease mechanism. Analysis of patients’ transcriptomic, methylation and immune data revealed impaired B cell development and maturation. We conclude that biallelic RNU6ATAC variants cause a novel syndrome of early-onset autoimmune diabetes and immune dysregulation. We further show that infancy-onset diabetes is a previously unrecognised feature of RNU4ATACopathy. Our work highlights the important role of two snRNAs critical to minor spliceosome function in immune system regulation, providing novel insights into the pathogenesis of autoimmune diabetes.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-10T18:00:32.637879+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001566","title":"Single-nucleus transcriptome sequencing of the ALS-FTD motor cortex after sorting by TDP-43 ","description":"Single-nucleus RNA-sequencing of NeuN+ nuclei of the post-mortem human primary motor cortex from patients with ALS-FTD confirmed for TDP-43 pathology, after sorting for TDP-43 signal, TDP-43 Low vs. TDP-43 High ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-30T16:38:21.002058+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001567","title":"Spatial predictors of response to immunotherapy in microsatellite stable metastatic colorectal cancer","description":"Microsatellite stable (MSS) colorectal cancers (CRC) are largely unresponsive to immune checkpoint inhibition (ICI), prompting investigation into strategies to enhance sensitivity. The MAYA trial, which utilized temozolomide (TMZ) in MGMT-silenced MSS mCRC, hypothesized that TMZ-induced hypermutation could sensitize tumors to ICI. This phase II trial met its primary endpoint, demonstrating durable clinical responses with TMZ combined with ipilimumab and nivolumab. To elucidate factors influencing response heterogeneity, we conducted multi-omic spatial profiling of samples from patients who participated in the MAYA trial, including baseline and on-treatment tissue and blood specimens. While increased neoantigen load following TMZ exposure did not consistently predict for deep responses, spatial profiling revealed key determinants. Lymphocyte proportions, particularly CD8+KI67+ cells, within stromal and tumor compartments, along with macrophage composition (CD68+CD163+ cells) at the tumor-stromal interface, were predictive of response. Treatment pressures dynamically altered the tumor microenvironment composition and activated peripheral immune cells. This study is the first to identify spatial predictors of response to this promising novel treatment approach for MSS CRC.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-04T15:54:43.018984+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001568","title":"Single cell RNA sequencing of tumor tissues from lung cancer patients with brain metastases","description":"Single-cell RNA sequencing (scRNA-seq) was conducted on a total of 252,641 cells obtained from 87 tumor tissues originating from 77 lung cancer patients, with and without brain metastases. Most of the specimens were collected from lymph nodes, followed by samples from the bronchus, lung, and pleura. The comprehensive single-cell profiles unveiled distinctive tumor-intrinsic characteristics and identified specific genes associated with brain metastasis.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001569","title":"Targeting type I regulatory T cells to enhance anti-parasitic T helper 1 and T follicular helper cell responses in human malaria","description":"Single-cell RNA sequencing (scRNA-seq) was performed on CD4⁺ T cells isolated from PBMCs of malaria-naïve volunteers inoculated with Plasmodium falciparum. Volunteers received antimalarial treatment, with or without the JAK1/2 inhibitor ruxolitinib.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-19T09:40:08.625325+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001570","title":"Single-cell sequencing data from AIM⁺ HIV-1-specific T cells in post-intervention controllers and non-controllers","description":"This study characterizes the transcriptional landscape and TCR repertoire of HIV-1–specific T cells across multiple longitudinal samples from two people living with HIV who achieved post-treatment viral control after short-course antibody-based therapy, compared with two non-controllers. Antigen-specific T cells were isolated by activation-induced marker (AIM)–based sorting prior to sequencing.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-30T16:34:56.164453+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001571","title":"Pre-existing immunity and hrHPV status as determinants of immunotherapy response in advanced penile cancer: biomarkers and overall survival in the PERICLES trial","description":"The phase II PERICLES trial (NCT03686332) investigated atezolizumab with or without radiotherapy in advanced penile cancer. Here, we report mature overall survival (OS) and updated progression-free survival (PFS) outcomes and an in-depth biomarker analysis. The goal was to perform an in-depth assessment of the tumor microenvironment to identify potential predictive biomarkers and cellular mechanisms underlying successful PD-L1 blockade response. \r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-19T14:14:57.42188+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001572","title":"Repotrectinib in NTRK fusion–positive advanced solid tumors: a phase 1/2 trial","description":"Early-generation TRK tyrosine kinase inhibitors (TKIs) approved for treating NTRK fusion–positive (NTRK+) solid tumors provide clinical benefit; however, resistance emerges. Repotrectinib is a next-generation ROS1/TRK TKI with a compact macrocyclic structure designed to improve durability of response. TRIDENT-1 is a registrational phase 1/2 trial assessing repotrectinib, a next-generation ROS1/TRK TKI, in adults with advanced solid tumors, including NTRK+ disease. The primary endpoint was confirmed objective response; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival and safety. Median follow-up ranged between 21.3 months and 25.7 months. In the TKI-naive cohort (n = 51; 95% confidence interval (CI)), the response rate was 59% (44–72); the median DOR was not estimable (NE); and the median PFS was 30.3 months (9.0–NE). In the TKI-pretreated cohort (n = 69; 95% CI), the response rate was 48% (36–60); the median DOR was 9.8 months (7.4–13.0); and the median PFS was 7.4 months (3.9–9.7). Of 30 TKI-pretreated patients with NTRK solvent front mutations, 16 had a response (53%; 95% CI: 34–72). Intracranial responses were observed in two of three TKI-naive patients and in four of six TKI-pretreated patients with measurable intracranial disease at baseline. Among all treated patients (n = 565), the most common any-grade treatment-related adverse event (TRAE) was dizziness (57%); most TRAEs were low grade; and 4% discontinued repotrectinib due to a TRAE. Overall, repotrectinib demonstrated durable systemic and intracranial responses with generally low-grade adverse events in patients with NTRK+ solid tumors, including those with previous TRK TKI treatment and solvent front mutations. These results support the use repotrectinib to treat patients with NTRK+ solid tumors. ClinicalTrials.gov identifier: NCT03093116 .","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-10T17:48:04.56067+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001573","title":"Multi-omic signatures in multiple myeloma","description":"Multiple myeloma (MM) is a genetically and clinically heterogeneous plasma-cell malignancy. Quadruplet therapy, combining anti-CD38 antibodies, immunomodulatory drugs, proteasome inhibitors, and dexamethasone, is now the standard induction treatment for newly diagnosed multiple myeloma (NDMM). To gain a comprehensive view of molecular changes in MM and their association with treatment response in this new standard care, we performed a multi-omic study of 423 NDMM from the MIDAS trial. \r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-20T16:30:56.974466+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001574","title":"Tremelimumab +/- durvalumab in combination with paclitaxel as immune induction in metastatic urothelial cancer: clinical and translational results of the ICRA trial","description":"DESCRIPTION: New therapeutic strategies for therapy-refractory metastatic urothelial carcinoma (mUC) patients are still needed. In the phase I-II ICRA trial, we evaluated whether paclitaxel plus tremelimumab (T; anti-CTLA-4), with or without durvalumab (D; anti-PD-L1), could induce a tumor response in mUC patients who had already received platinum chemotherapy and immune checkpoint inhibition (ICI). After a dose-escalation safety phase, patients were randomized between three arms: A (n=20 after expansion) paclitaxel plus T750mg (cycles 2-8); B (n=12) paclitaxel plus T300mg (cycle 2) plus D1500mg (cycles 2-13); C (n=12) T750mg (cycles 1-7). The objective response rate in arm A was 26% (88% confidence interval (CI) = [14,36%]) versus 17% (88% CI = [3,42%]) in arm B and 8% (88% CI = [0.3,33%]) in arm C. Grade 3-4 treatment-related adverse events occurred in (A) 45%, (B) 75%, and (C) 25% of patients. Murine experiments showed attenuated tumor outgrowth for paclitaxel plus anti-CTLA-4 compared to monotherapy with either agent. Transcriptomic analyses showed upregulation of inflammation signatures in on-treatment tumor tissue biopsies. This study demonstrated encouraging antitumor activity in therapy-refractory mUC treated with paclitaxel plus high-dose anti-CTLA-4 and suggests immune induction may still be possible after failure to anti-PD-(L)1 therapy. PROJECT GOAL: We aimed to explore both potential biomarkers for response to combination ICB, as well as treatment dynamics to gain a better understanding of the effects of ICB on the urothelial cancer tumor microenvironment (TME).\r\n","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-30T16:19:46.937813+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001575","title":"A New CA19-9 Cut-Off Value Identifies Lewis Antigen Status and Refines Prognostic Stratification in PDAC","description":"This study investigates the clinical utility of serum CA19-9 levels in pancreatic ductal adenocarcinoma (PDAC), with a focus on identifying patients with Lewis antigen–negative status due to germline FUT3 variants. Using data from multicenter prospective cohorts in Taiwan, we analyzed CA19-9 classification, FUT2/FUT3 genotypes, and clinicopathological annotations. The goal of this study is to refine prognostic stratification and reduce false-negative interpretation of CA19-9 in PDAC patients. All participants provided informed consent, and the study was approved by the relevant institutional review boards.\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-13T13:26:45.902969+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001576","title":"Tumor immune microenvironment reconstitution in patient-derived organoids enables therapy modeling for NSCLC","description":"Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality. Despite various therapeutic options, treatment resistance is common, underscoring the need for effective combination therapies and reliable pre-clinical models for patient-specific evaluation. Here, we describe strategies for reconstituting tumor immune microenvironment (TIME) components within patient-derived tumor organoid (PDTO) cultures. We established a tumor processing pipeline enabling concurrent expansion of tumor-infiltrating lymphocytes (TILs) and PDTO generation from the same resection. We optimized scalable assays to assess IFN-γ secretion and T-cell cytotoxicity with immune checkpoint inhibitors (alone or combined) and targeted inhibitors, capturing inter-patient heterogeneity and intra-patient variations between TILs and PBMCs. Additionally, we developed methods for differentiating PDTO-specific tumor-associated macrophages (TAMs) and established PDTO-TAM co-culture systems to evaluate TAM effects on PDTO growth and chemotherapy sensitivity. All approaches are scalable to high-throughput levels, highlighting the value of TIME-PDTO co-cultures for therapeutic modeling and precision medicine","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001577","title":"Tracing the molecular route to progression in miRNA biogenesis-defective thyroid lesions","description":"Alterations in the DICER1 and DGCR8 microprocessor genes confer risk to the development of benign and malignant thyroid lesions. The involvement of 2 miRNA biogenesis genes in benign and malignant thyroid tumors highlights the key role of miRNAs in the thyroid gland.\r\n\r\nWe traced the progression from benignity to malignancy in DICER1- and DGCR8-mutated thyroid lesions by performing a multiomic characterization of these lesions aiming to uncover unique features characterizing either form for potential use as biomarkers. This multiomic characterization included whole exome sequencing (WES) (N=18), miRNA profiling (N=38), spatial transcriptomics (N=2) and/or methylome (N=281). \r\n","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001578","title":"3D chromatin contacts of iPSC (controls) and mDAN (differentiated neurons) cells","description":"Sequencing of 3 replicates per condition to gather insights on the 3D chromatin conformation of iPCS-derived neuronal progenitors (smNPCs) and mDANs using LowC. The downstream analysis studies changes in A and B compartment interactions and in topologically associated domains (TADs). ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-05T16:21:03.713781+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001579","title":"ATAC-seq iPSC cells or smNPC cells for allelic imbalance","description":"In order to confirm the predicted impact of the PD-associated allele of rs144814361 on BAG3 promoter, we proceeded with genome editing of the TH-REP1 cell line by using prime editing to insert the “T” allele at the position chr10:119651405 in the BAG3 promoter.\r\n3 replicates for each condition: 1) iPSC Wild Type 2) SNP-BAG3 variant in iPSC 3) SNP-BAG3 variant in smNPC.\r\nAllelic imbalance is further assessed using read counting at this specific position.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-05T16:21:03.713781+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001580","title":"WNT5a+ CAF-driven epithelial plasticity drives tumor progression in CRC","description":"The development of colorectal cancer (CRC) is profoundly shaped by the tumor microenvironment (TME), with cancer-associated fibroblasts (CAFs) serving as key drivers of this process. In this study, we characterized CAF subtypes, their origin and function in CRC, as well as important stimuli for the transition. Top crypt fibroblasts (CTFs) - normally involved in epithelial differentiation - as the source of F3+ CAFs, which are Wnt5a-positive, expand in CRC, and associate with immunotherapy resistance. Functional experiments demonstrate that fibroblast-specific ablation of WNT5a significantly reduces tumor burden in an inflammation-driven CRC model and suggest a mechanistic link between fibroblast-derived WNT5A and the maintenance of pro-tumorigenic epithelial states. These findings provide new insights into CAF-driven epithelial plasticity and highlight the WNT5A axis as a potential therapeutic target in CRC.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001581","title":"Multiplexed biomarkers dynamically detect heterogeneous residual neuroblastoma cell clone activity in the bone marrow niche","description":"Our objective was to develop a patient-specific, genomics-informed minimal residual disease (MRD) monitoring strategy for pediatric high-risk neuroblastoma using individualized multiplexed mediator-probe PCR (MP-PCR) assays. Tumor-specific somatic mutations or structural variants were identified through hybrid-capture panel sequencing. We examined tumor material from 8 patients, including 11 primary tumor samples, 3 of which represent spatially distinct primary tumor samples and 2 samples obtained at relapse. Provided are FASTQ data files, bam and bambai files, as well as breakpoint spanning and encompassing read (enspan) bam and bambai files. Sequencing bam data files are aligned to GRCh37.p13 reference genome (processed). Sequencing data were aligned to the GRCh37.p13 reference genome and processed using validated pipelines.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-24T12:19:17.385345+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001582","title":"Multiomic cell-free DNA profiling to inform molecular classification and immunotherapy outcomes in endometrial cancer","description":"This study involved a cell-free DNA (cfDNA) framework integrating genomic, transcriptomic and epigenomic profiling to investigate patient response to immune checkpoint inhibitors in advanced endometrial cancer (EC) with mismatch repair deficiency (dMMR).","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-24T10:51:58.0626+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001583","title":"Osteosarcoma 3D patient derived cultures to test genome-informed personalized treatment options; a feasibility study","description":"Background: Improving osteosarcoma treatment beyond conventional (neo)adjuvant chemotherapy and resection remains challenging. An urgent need for novel therapeutic options, particularly personalized and targeted approaches, has emerged due to high inter-patient molecular heterogeneity. A lack of representative in vitro and in vivo models impedes therapeutic development, therefore we aimed to create 3D in vitro long term culture models directly from patient material.\r\n\r\nMethods: Tumour cells from seven osteosarcoma patients were propagated in monolayer or collagen hydrogels, while whole-exome sequencing of corresponding primary tumour tissue was performed to identify potential drug targets. Established cultures were subsequently used to assess efficacy of the identified personalized treatment options.\r\n\r\nResults: Three out of seven hydrogel cultures harboured the same genetic alterations as the corresponding primary tumours. Among these, the L6565 patient line exhibited homozygous CDKN2A loss with retained Rb expression, rendering tumour cells sensitive to CDK4/CDK6 inhibition via palbociclib. This patient line was used to evaluate genome-informed therapy and to compare cell culture models of increasing complexity. Our findings demonstrate feasibility of establishing long-term patient-derived osteosarcoma cultures with a success rate of 14%. Tumour heterogeneity was reflected in advanced culture methods producing more variability in treatment response. \r\n\r\nConclusion: These results highlight the potential of genome-informed therapies in osteosarcoma and the importance of refining culture techniques to enhance translational research and therapeutic outcomes.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-18T17:41:25.197231+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001584","title":"Single-cell RNA sequencing of SI-NET","description":"Small intestinal neuroendocrine tumors (SI-NETs) arise from hormone-producing cells in the gut, yet the molecular changes driving malignant transformation remain poorly understood. Bulk tissue-based analyses make it challenging to distinguish signals derived from normal cells from those of normal hormone-producing cells. In this study, we analyzed SI-NETs at single-cell resolution and directly compared tumor cells with their corresponding normal hormone-producing counterparts using single-cell RNA sequencing. Tissue samples were obtained from two patients undergoing tumor resection surgery. Cells from corresponding normal intestinal mucosa and SI-NET tumors were isolated using specific markers and analyzed for direct comparison.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-01-30T10:38:39.863016+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001585","title":"Sequencing data from triple-negative breast cancer tumors","description":"Autoimmunity and anti-cancer immunity lie on the same biological continuum1,2, but their link remains obscure. The paraneoplastic neurological syndrome anti-NMDA receptor (NMDAR) encephalitis (ANRE) is a paradigm for their connectivity3 given that intratumoral NMDAR expression correlates with the generation of anti-NMDAR antibodies4,5. Here, we verify ectopic expression of GluN1 and GluN2B NMDAR sub-units in triple-negative breast cancer (TNBC)6 and model this using orthotopic TNBC tumors with inducible expression of GluN1-GluN2B NMDARs. We show that NMDAR expression is sufficient to induce B cell recruitment and their affinity maturation, consistent with an integrated adaptive immune response. Reconstruction of extended intratumoral B cell phylogenies and cryo-EM structural analyses demonstrated that affinity-matured hypermutated and class-switched antibodies emerged from pre-existing germline-configuration lower-affinity anti-NMDAR antibodies. Distinct matured antibodies targeted specific epitopes and induced conformational rearrangements within the NMDAR amino-terminal domain, predictive of their functional effects, ranging from inhibition to potentiation. Passive transfer of an NMDAR-potentiating antibody caused autonomic dysregulation and lowered the seizure threshold in healthy female mice, recapitulating key diagnostic criteria of ANRE4,5. We further identify a correlation between intratumoral NMDAR expression and anti-NMDAR antibody titers in TNBC patients. Taken together, our data establish a direct connection between intratumoral NMDAR expression, antibody maturation, and the onset of autoimmunity. These findings suggest that germline-encoded anti-NMDAR antibodies contribute to immune surveillance but can also trigger autoimmune disease upon maturation, revealing a mechanistic tradeoff between cancer immunity and neurotoxicity.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-30T13:44:53.143664+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001586","title":"Distinct immune and genomic signatures predict resistance to ibrutinib therapy in Waldenström macroglobulinemia","description":"In this study, we investigate the complex interplay between tumour-acquired genetic features and the composition of the microenvironment in the promotion of ibrutinib resistance in WM patients by integrating single-cell RNA sequencing (scRNAseq) and whole-genome sequencing (WGS), to examine bone marrow tumour and immune compartments from 37 symptomatic WM patients treated with ibrutinib.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-07T10:34:36.389949+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001587","title":"IMMUcan BC1 cohort","description":"The goal of IMMUcan is to understand how the immune system interacts with tumors and how therapeutic interventions influence this interaction. This cohort includes metastatic Triple Negative Breast Cancer (mTNBC) patients, naïve of treatment in the metastatic settings, treated in 1st line with chemotherapy or chemo-immunotherapy Comprehensive profiling data are integrated with longitudinally collected clinical information. Cellular profiling of the same tumor samples was performed using multiplex immunofluorescence imaging, imaging mass cytometry, and H&E staining.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-05T10:50:23.070547+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001588","title":"Genomic determinants of treatment outcome and identification of a new genomic subset of adult acute lymphoblastic leukemia from the ECOG-ACRIN E1910 randomized phase III trial","description":"B-cell acute lymphoblastic leukemia (B-ALL) is rare in adults but the prognosis remains inferior to children. To comprehensively define the genomic landscape of B-ALL in adults, we analyzed 569 cases by transcriptome, genome and exome sequencing. Our integrated genomic analyses identified 22 molecular subtypes of adult B-ALL, with an additional 268 driver genes identified as secondary genomic alterations that contributed to the enrichment of significantly altered biological pathways. We identified a subgroup of adult B-ALL characterized by overexpression of CEBPA or CEBPB in 3.5% of cases by a variety of genomic mechanisms including chromosomal translocation and noncoding mutations that result in enhancer hijacking or the formation of de novo enhancers downstream of CEBPA. The addition of blinatumomab to chemotherapy improved the outcome for several high-risk B-ALL subgroups, including hyperdiploid, PAX5alt, PAX5 P80R, BCR::ABL1-like with CRLF2 rearrangements and KMT2A-rearranged ALL. Alteration of TP53 or mutations associated with myeloid clonal hematopoiesis (MyM) were identified in 15.3% and 9.8% of patients assessed, respectively. The presence of these mutations was associated with increased age at diagnosis and inferior outcome to chemotherapy, whilst blinatumomab rescued this poor outcome, especially for patients with MyM. Together we provide a comprehensive genomic analysis of adult B-ALL and provide guidance on the use of blinatumomab in high-risk subtypes.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001589","title":"A single-cell atlas of meningioma.","description":"In this study, we examined the breadth of cell types and states in meningioma using the largest single-cell cohort of meningioma by generating more than 7.5 million total cells from meningioma and surrounding dura, profiled using single-nuclear RNA sequencing and high-resolution spatial transcriptomics.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-21T16:53:29.695768+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001590","title":"scD&D-seq of mobilized PBMC from a healthy individual having IDH2 R140Q CHIP","description":"Single-cell D&D-seq profiles from a mobilized CHIP (clonal hematopoiesis of indeterminate potential) PBMC sample (2 replicates) co-profiled with IDH2 R140Q GoT-ChA. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-25T11:24:15.589932+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001591","title":"Classification of triple negative breast cancer - RNA-Seq","description":"Previous studies aiming at TNBC tumor classification and patient stratification based on transcriptome and proteome profiling defined several TNBC subgroups, however different outputs in various studies resulted in a lack of consensus on the TNBC classification. As proteins are the molecular effectors and targets of therapy, we hypothesize that TNBC tumor classification utilizing next-generation proteomics in combination with other omics approaches would reflect tumor biology more accurately. This dataset represents RNA-Seq and WES complement of proteomics data deposited in PRIDE proteomics repository. Our data is complementary to previous classifications, further unravel TNBC molecular heterogeneity and identify cluster-specific proteins associated with patient survival. This work presents a multiomics TNBC classification that can lead to more accurate patient stratification, identifying core pathways, proteins and complexes which could potentially serve as targets of biological therapy. RNA-Seq part.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001592","title":"Classification of triple negative breast cancer - WES","description":"Previous studies aiming at TNBC tumor classification and patient stratification based on transcriptome and proteome profiling defined several TNBC subgroups, however different outputs in various studies resulted in a lack of consensus on the TNBC classification. As proteins are the molecular effectors and targets of therapy, we hypothesize that TNBC tumor classification utilizing next-generation proteomics in combination with other omics approaches would reflect tumor biology more accurately. This dataset represents RNA-Seq and WES complement of proteomics data deposited in PRIDE proteomics repository. Our data is complementary to previous classifications, further unravel TNBC molecular heterogeneity and identify cluster-specific proteins associated with patient survival. This work presents a multiomics TNBC classification that can lead to more accurate patient stratification, identifying core pathways, proteins and complexes which could potentially serve as targets of biological therapy. WES part.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001593","title":"Structural Forms of ERBB2 Amplification and Their Clinical Significance in EAC Brain Metastases","description":"We characterized the genomic architecture, evolutionary history, and tumor microenvironment of EAC brain metastases from 65 patients using whole-genome sequencing, single-cell spatial transcriptomics, and ERBB2 fluorescence in situ hybridization. We retrospectively identified patients who underwent neurosurgical resection for brain metastases arising from esophageal adenocarcinoma. Whole-genome sequencing was performed using a hybrid strategy that combined Oxford Nanopore long-read sequencing with Illumina short-read sequencing to enable high-resolution detection of copy number alterations and complex structural variants. This study identifies ERBB2 amplification as a dominant genomic feature of esophageal adenocarcinoma brain metastases and demonstrates that the structural organization of this amplicon is associated with clinical behavior. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001594","title":"SPEN loss drives extra-follicular diffuse large B cell lymphoma with female-specific lethality and TLR pathway therapeutic vulnerabilities","description":"Multiome (ATAC and GEX) sequencing for one rLN sample and one DLBCL sample","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-09T09:42:08.355112+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001595","title":"RNA sequencing of untreated head and neck cancer patient-derived xenografts (PDXs) and matched patient tumor tissue.","description":"RNA sequencing was performed on untreated patient tumor tissue and matched patient-derived xenograft (PDX) models of primary head and neck squamous cell carcinoma (HNSCC). The aim of this analysis was to characterize the transcriptional landscape of the tumors in the in vivo setting.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-17T17:07:33.000046+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001596","title":"Single-cell multi-omics reveals clonal evolution and T-cell dynamics underlying differential responses to ibrutinib in Waldenström macroglobulinemia. ","description":"To elucidate the molecular basis underlying differential response and resistance to ibrutinib in Waldenström’s macroglobulinemia (WM), we conducted a prospective phase II trial (NCT02604511) of ibrutinib monotherapy in treatment-naïve patients. Seventy-four sequential bone marrow (BM) aspirates from 17 patients, collected from baseline through 48 treatment cycles, were profiled using single-cell RNA and V(D)J sequencing.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-10T15:50:36.199436+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001597","title":"Genomic and Transcriptomic Quality Control for an Autologous iPSC-Derived Cell Therapy for Parkinson’s Disease","description":"This is a multimodal study, integrating RNAseq, whole genome sequencing (WGS), and microarray data to support the development and validation of a novel autologous iPSC-derived dopaminergic neuron therapy for Parkinson’s disease (PD).\r\nIn this study, we present preclinical data and our manufacturing strategy for developing an autologous iPSC-derived dopaminergic neuron therapy for PD. Our approach addresses prior safety concerns by implementing whole genome sequencing at multiple stages of iPSC derivation and differentiation. To address the challenge of reproducibly qualifying individual cultures of DANPCs for optimal efficacy (Jeon, Cha et al. 2025), we developed a novel  transcriptomic assay, “NeuriTest”, which identifies the optimal differentiation stage for engraftment and efficacy. Using the PluriTest model (Muller, Schuldt et al. 2011), NeuriTest was created by generating a reference database of gene expression profiles and using machine learning to identify profiles that correlate with efficacy. In contrast to scale-up processes used for allogeneic products, we employ a cost-effective fail-fast manufacturing paradigm that identifies quality control failures early in the process. The data reported here underpin the launch of ASPIRO, the first multicenter Phase 1/2a clinical trial of autologous iPSC-derived dopaminergic neuron replacement for PD (ClinicalTrials.gov ID: NCT06344026), with initial dosing completed in 2024.  This data supports the genomics quality control metrics we developed to support this novel personalized therapeutic approach.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-17T17:00:19.900437+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001598","title":"Sequencing data from triple-negative breast cancer tumors","description":"Autoimmunity and anti-cancer immunity lie on the same biological continuum1,2, but their link remains obscure. The paraneoplastic neurological syndrome anti-NMDA receptor (NMDAR) encephalitis (ANRE) is a paradigm for their connectivity3 given that intratumoral NMDAR expression correlates with the generation of anti-NMDAR antibodies4,5. Here, we verify ectopic expression of GluN1 and GluN2B NMDAR sub-units in triple-negative breast cancer (TNBC)6 and model this using orthotopic TNBC tumors with inducible expression of GluN1-GluN2B NMDARs. We show that NMDAR expression is sufficient to induce B cell recruitment and their affinity maturation, consistent with an integrated adaptive immune response. Reconstruction of extended intratumoral B cell phylogenies and cryo-EM structural analyses demonstrated that affinity-matured hypermutated and class-switched antibodies emerged from pre-existing germline-configuration lower-affinity anti-NMDAR antibodies. Distinct matured antibodies targeted specific epitopes and induced conformational rearrangements within the NMDAR amino-terminal domain, predictive of their functional effects, ranging from inhibition to potentiation. Passive transfer of an NMDAR-potentiating antibody caused autonomic dysregulation and lowered the seizure threshold in healthy female mice, recapitulating key diagnostic criteria of ANRE4,5. We further identify a correlation between intratumoral NMDAR expression and anti-NMDAR antibody titers in TNBC patients. Taken together, our data establish a direct connection between intratumoral NMDAR expression, antibody maturation, and the onset of autoimmunity. These findings suggest that germline-encoded anti-NMDAR antibodies contribute to immune surveillance but can also trigger autoimmune disease upon maturation, revealing a mechanistic tradeoff between cancer immunity and neurotoxicity.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-30T13:44:56.392691+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001599","title":"Whole genome sequencing data of paediatric ETV6::RUNX1 acute lymphoblastic leukemia","description":"ETV6::RUNX1 (E::R) subgroup is the second most frequent form of B cell acute lymphoblastic leukemia (B-ALL) in childhood. This subgroup of ALL generally presents with low-risk features and responds well to chemotherapy with ensuing favorable prognosis. Some patients, however, have a slow response to induction treatment and carry increased risk for relapse.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-17T17:17:01.699122+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001600","title":"CRISPR Dependency Screening Identifies a METTL3- ATM Regulatory Loop Vulnerable to Drug Inhibition in Cancer Cells","description":"The occurrance of aberrant patterns of RNA modifications and the disruption of the associated RNA writers, erasers and readers genes are recently identified as hallmarks of human cancer. Herein, we performed a CRISPR-Cas9 library screening by combining targeting of 2,508 genes involved in epigenetic regulation and DNA repair with the  METTL3 inhibitor STM2457 to identify functional vulnerabilities for the epitranscriptomic drug. One actionable target providing increased sensitivity to STM2457 upon CRISPR-Cas9 loss was the Ataxia Telangiectasia Mutated (ATM) gene.Using genetically-induced, naturally defective and drug inhibition mediated approaches we validated that ATM loss rendered sensitivity to METTL3 blockage.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001601","title":"LySeqST: A targeted sequencing assay for robust genomic classification of diffuse large B-cell lymphoma","description":"Diffuse large B-cell lymphoma (DLBCL) is a biologically heterogeneous disease. Two genomic classification systems, LymphGen and DLBclass, are capable of reproducibly classifying single tumors into subtypes with prognostic relevance in the context of standard-of-care R-CHOP chemoimmunotherapy. Preliminary data from subgroup analyses of clinical trials suggest that the distinct biological features are targetable with drugs that exploit subtype-specific vulnerabilities, and large clinical trials are being designed to test this hypothesis. Although whole exome sequencing (WES) remains the gold standard for each of these classification systems, many laboratories may opt for smaller targeted sequencing panels that reduce costs associated with sequencing, data storage, and processing. Here, we describe the design and validation of a targeted sequencing panel (LySeqST) that captures the genomic features required specifically for LymphGen classification. We perform in silico and real-world validation vs. WES data and demonstrate that LySeqST can be used to accurately classify DLBCL tumors. In an unselected population-based cohort, we determine the real-world proportions and validate the prognostic relevance of LymphGen subtypes, confirming that only tumors expressing the dark zone gene expression signature are consistently associated with inferior outcomes. Our results support the use of LySeqST for accurate genomic classification of DLBCL.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-16T10:27:36.53893+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001602","title":"Transcriptomics analysis of biopsy and resected material from HCC and matched non-tumor","description":"We hypothesize that pre-analytical handling such as surgery procedure and cold ischemia have significant effects on omics data derived from liver and liver tumor tissue that may confound classification of tumor subtypes of hepatocellular carcinoma. This study is aimed at revealing such effects by comparing resection samples with patient matched biopsy samples in a multi-omics analysis.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-04T16:02:33.077879+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001603","title":"Whole-genome sequencing study of uveal melanoma","description":"Uveal melanoma is the most common primary intraocular cancer, characterized by metastasis-related mortality. Here, we explored whole-genome sequences from 40 primary uveal melanomas to illustrate the landscape of genomic mutations and investigate their association with prognosis.\r\n","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-19T11:34:28.12084+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001604","title":"Oncogenic drivers shape the tumor microenvironment in human gliomas","description":"Oncogenic mutations in gliomas have been well-characterized, their impact on the tumor microenvironment remains poorly understood. To investigate how genomic alterations may influence the glioma microenvironment, we performed an integrative multiomic and spatial transcriptomic analysis of 93 glioma samples (46 IDH-mutant gliomas and 47 IDH-wildtype glioblastoma) from 69 patients representing both primary and recurrent stages. Using whole-genome sequencing, chromatin conformation capture (Hi-C), RNA-seq, and single-cell spatial transcriptomics (Xenium), we defined how major driver mutations influence spatial tumor organization. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001605","title":"Precision tumor-on-chip for personalized assessment of drug efficacy and immune cell delivery","description":"Tumor heterogeneity and drug resistance limit the efficacy of cancer therapies and highlight the need for patient-specific preclinical models. We developed a microfluidic tumor-on-chip (TOC) platform that integrates patient-derived organoids with a functional endothelial barrier to recreate drug and immune cell transport from the vasculature into tumor tissue. This system enables evaluation of therapeutic efficacy, toxicity, and immune cell migration under physiologically relevant conditions. In a clinical pancreatic cancer case, the TOC model predicted treatment resistance and uncovered gene expression shifts and pathway rewiring at single-cell resolution. By simulating vascular drug transport, the platform provides a scalable and clinically relevant tool for studying treatment response mechanisms and tailoring cancer treatments. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001606","title":"scD&D Multiome of GATA1 regulatory network dynamics during erythropoiesis ","description":"Ex vivo differentiation experiments of human CD34+ hematopoietic stem and progenitor cells and profiled cells along the erythropoietic trajectory at multiple timepoints (differentiation days 0, 5, 8, 18, and 24), for simultaneous assessment of transcriptome, chromatin accessibility and GATA1 binding","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-25T11:30:55.400784+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001607","title":"Long-read whole genome sequencing of gastric cancer","description":"Gastric cancer (GC) remains a significant health challenge globally, with a particularly high incidence in Asia, including Singapore. Understanding the genomic landscape of normal gastric and the different GC subtypes along with its precursor lesions such as intestinal metaplasia (IM) as well as GC metastatic sites is crucial for advancing diagnostics, prognostics, and therapeutics. Long-read sequencing technologies offer an opportunity to delve deeper into the genomic and epigenetic alterations underlying these conditions and to complement existing short-read omics data. By integrating these data with previously generated in-house multi-omics data (such as RNA sequencing and whole exome sequencing), we hope to better elucidate the molecular mechanism underlying GC initiation and progression.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-16T10:24:48.798609+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001608","title":"A conserved enhancer in ecDNA-containing Medulloblastoma","description":"Extrachromosomal DNA (ecDNA) fundamentally reshapes the regulatory landscape of cancer cells by providing a platform for massive oncogene amplification and heightened chromatin accessibility. This research investigates how ecDNA-resident enhancers operate within large-scale molecular hubs to drive potent, long-range transcriptional activation that transcends standard chromosomal boundaries. By analyzing the unique structural configurations of these elements, the work identifies key mechanisms that contribute to rapid tumor evolution and significant phenotypic plasticity. These findings highlight the critical role of non-chromosomal regulatory elements in maintaining oncogenic signaling and suggest new avenues for therapeutic intervention in aggressive, ecDNA-driven malignancies.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-10T14:24:52.554328+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001609","title":"A conserved enhancer in ecDNA-containing Medulloblastoma","description":"Extrachromosomal DNA (ecDNA) fundamentally reshapes the regulatory landscape of cancer cells by providing a platform for massive oncogene amplification and heightened chromatin accessibility. This research investigates how ecDNA-resident enhancers operate within large-scale molecular hubs to drive potent, long-range transcriptional activation that transcends standard chromosomal boundaries. By analyzing the unique structural configurations of these elements, the work identifies key mechanisms that contribute to rapid tumor evolution and significant phenotypic plasticity. These findings highlight the critical role of non-chromosomal regulatory elements in maintaining oncogenic signaling and suggest new avenues for therapeutic intervention in aggressive, ecDNA-driven malignancies.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-10T14:24:49.740802+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001610","title":"A conserved enhancer in ecDNA-containing Medulloblastoma","description":"Extrachromosomal DNA (ecDNA) fundamentally reshapes the regulatory landscape of cancer cells by providing a platform for massive oncogene amplification and heightened chromatin accessibility. This research investigates how ecDNA-resident enhancers operate within large-scale molecular hubs to drive potent, long-range transcriptional activation that transcends standard chromosomal boundaries. By analyzing the unique structural configurations of these elements, the work identifies key mechanisms that contribute to rapid tumor evolution and significant phenotypic plasticity. These findings highlight the critical role of non-chromosomal regulatory elements in maintaining oncogenic signaling and suggest new avenues for therapeutic intervention in aggressive, ecDNA-driven malignancies.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-10T14:24:58.234487+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001611","title":"Insights into Adult Gut Microbiota Composition Using the Estonian Cohort","description":"This study explores the gut microbiota of 1,826 adult individuals, predominantly from the Estonian population. The cohort includes 16S rRNA gene V4 region amplicon sequencing data along with metadata, such as age, sex, health status, anthropometric parameters, and stool consistency. The research aims to characterise the microbial community structure, identify distinct enterotypes, and examine their associations with host characteristics. The dataset provides a valuable reference for understanding gut microbiota composition and supports research in personalised nutrition and lifestyle-related health strategies.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-18T17:27:40.145758+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001612","title":"Three-Dimensional Epigenome Roadmap of Human B-cell Differentiation","description":"Human B-cell differentiation underlies humoral immunity, and its disruption leads to cancer, autoimmunity, and immunodeficiencies. However, the enhancer-based regulatory mechanisms governing this process remain poorly understood. To address this gap, we generated the first three-dimensional epigenomic roadmap of in vivo human B-cell differentiation. By profiling nine differentiation stages, we linked nearly half a million enhancers to their target genes through long-range chromatin interactions, defined their activity states, and predicted bound transcription factors. We show that the acquisition of B-cell identity, distinct from common cellular processes, relies on large enhancer networks acting additively and synergistically to finely tune transcription. We further identify a 3D epigenetic priming mechanism underlying immune memory, whereby memory B cells retain primed DNA loops that enable faster responses to antigen re-exposure. Extending this roadmap to disease, we demonstrate that B-cell malignancies preserve enhancer signatures of their cell of origin while silencing distal tumor suppressor control. Finally, we uncover a previously unappreciated oncogenic mechanism in which intragenic deletions disrupt distal gene regulation via enhancer loss. Together, this resource provides a framework for understanding the genetic and epigenetic basis of humoral immunity and immune-related diseases.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001613","title":"Study of the role of aneuploidy in cB-ALL","description":"We modeled two proposed routes to hyperdiploidy, chromosome missegregation and cytokinesis failure, by transiently exposing human fetal liver–derived HSPCs to reversine or cytochalasin-D. Induced hyperdiploidy impaired fitness and delayed differentiation in vitro, causing hyperdiploid cells to be rapidly outcompeted by euploid counterparts. Nonetheless, hyperdiploid cells engrafted immunodeficient mice, where rare clones persisted long-term and acquired non-random chromosomal gains frequently observed in cB-ALL. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-25T10:44:57.610156+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001614","title":"Optimized large-scale longitudinal biorepository of gastroesophageal adenocarcinoma patient-derived organoids","description":"To enable translation studies we created patient derived models to assess biomarkers, target validation, and patient response. To evaluate that the PDOs retain the genomic characteristics of the primary tumours we performed (WES) sequencing of 11 matched primary tumours and their matched organoid samples (total n=22). Libraries were sequenced using Illumina NovaSeq technology. Reads were aligned with BWA alignment to hg38. Files were processed following GATK best practices (version GATK 4.2.3.0). Variants were called using Mutect2. The dataset contains the alignmnent files (.bam) and the called mutations (.vcf). ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-26T12:55:01.27345+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001615","title":"Single-nucleus profiling of severe alcohol-related hepatitis ","description":"Single-nucleus profiling of severe alcohol-related hepatitis reveals immune and parenchymal states behind corticosteroid response.\r\nSingle-nucleus RNA sequencing was performed on liver biopsies from patients with biopsy-proven sAH (n=17), including paired baseline and day 8 biopsies in a subset (n=8). Patients were classified as corticosteroid responders (sAH-R; Lille score <0.45) or non-responders (sAH-NR; Lille score ≥0.45). Liver biopsies from patients with acute decompensation of alcohol-related liver disease (AD; n=5) and healthy controls (n=4) were included for comparison.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-30T15:17:38.119011+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001616","title":"PanProstate Cancer Group DK data","description":"THE PAN PROSTATE CANCER PROJECT: Many groups around the world have generated Whole Genome DNA Sequence (WGS) data from prostate cancer patients. The pan prostate group have gathered with the idea that the accumulated data, should be collected and compared in a common format including common storage, re-analysis through a single pipeline, and investigation to achieve a variety of scientific goals. The combined collection would include the following categories: (i) cancers from different ethnic groups: eg Caucasian, Asian, Black Caribbean; (ii) cancer from different stages of progression from normal, to organ-confined disease, to metastases; (iii) early-onset prostate cancer; (iv) prostate cancer from aggressive and indolent disease; and (v) prostate cancer patients managed by different treatments with information linked to long-term clinical follow up data in many cases.This study contains the samples from the Danish prostate group.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-05T11:49:23.636923+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001617","title":"Single-nucleus RNA sequencing and spatial transcriptomics of choroid plexus tumours and non-neoplastic choroid plexus (raw and processed data)","description":"Our study leverages single-nucleus RNA sequencing (~124,500 nuclei) and spatial transcriptomics (~40,650 spots) to dissect the molecular architecture of CPTs. We generated a comprehensive transcriptomic atlas of 45 CPT samples spanning all three methylation groups and a reference cohort of 16 non-neoplastic choroid plexus (ChP) samples, spanning foetal, paediatric and adult specimens. Key discoveries from this investigation include that paediatric B tumorus exhibit a dedifferentiated state and enrichment of stress-related metaprograms, including hypoxia, TGFß signaling, Interferon I signaling and early stress response, that correlate with poor clinical outcome and antagonise multiciliogenesis. On a spatial level, these stress-linked programs co-localise with immunosuppressive, pro-angiogenic microenvironment, suggesting a link between developmental arrest, microenvironmental remodelling and aggressive behaviour.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-24T12:53:52.530603+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001618","title":"Viral evasion Strategy for Generating Hypoimmunogenic hiPSC Lines","description":"Mismatches in HLA haplotypes between donors and recipients significantly increase the risk of graft failure due to immune rejection. To address these limitations, we introduced a cytomegalovirus-derived US2 encoding sequence into the AAVS1 safe-harbor locus of a human induced pluripotent stem cell (hiPSC) line. US2 expression in iPSC abolished HLA-A2 alloreactive T-cell activation without increasing NK cell degranulation, indicating preserved inhibitory signaling.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-23T15:10:17.173058+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001619","title":"Somatic copy number alterations profiling in non-small cell lung cancer and their correlation with clinical efficacy in first-line treatment","description":"Genomic data from FFPE tumor samples of patients with non-small cell lung cancer (NSCLC), profiled by shallow whole-genome sequencing (sWGS). The study aimed to characterize somatic copy number alterations (SCNAs) and SCNA burden to assess their clinical relevance for patient stratification across different first-line treatments.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-10T14:08:58.754878+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001620","title":"Whole-genome sequencing of cell-free DNA from pancreatic and breast cancer cohorts for fragmentomic and tumor fraction analysis","description":"This project provides whole-genome sequencing data from cell-free DNA collected from patients with pancreatic ductal adenocarcinoma and breast cancer, alongside healthy and benign controls. The study aims to identify novel liquid biopsy biomarkers by exploring the relationship between per-base quality scores and fragmentomic signals like end-motifs and fragment length. Furthermore, the data supports the development of Bayesian deep learning frameworks for the uncertainty-aware estimation of tumor fraction and ploidy in low-concentration clinical samples.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-25T11:46:45.379451+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001621","title":"IFNγ Drives Long-Term Bone Marrow Niche Dysfunction Following Doxorubicin-Based Chemotherapy","description":"To understand the impact of chemotherapy treatment on the bone marrow microenvironment, we acquired paired bone marrow (BM) aspirate samples from patients with acute lymphoblastic leukemia (ALL) collected at diagnosis and 4w later (end of induction therapy) at the Princess Margaret Hospital.  The BM stroma was obtained by expanding BM aspirates in culture, and profiled by RNA-sequencing. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-17T16:09:10.902528+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001622","title":"Whole-exome sequencing (WES) analysis of untreated head and neck cancer patient-derived xenografts (PDXs) matched patient tumor tissue and normal mucosa tissue.","description":"WES analysis was performed on untreated patient tumor/normal mucosa tissue and matched patient-derived xenograft (PDX) models of primary head and neck squamous cell carcinoma (HNSCC) to investigate the preservation of tumor-specific genomic alterations in the in vivo context.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-25T15:22:42.735801+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001623","title":"Transcriptional and epigenetic profiling of bone marrow blood progenitors across age","description":"Bone marrow from donors without known malignancy was isolated and CD34-enriched, FACS-purified to further enrich for CD34+CD38- primitive cells, and then profiled by single-cell 10X genomics chromium Multiome (RNA+ATAC).","abstract":null,"study_type":"RNASeq","pubmed_ids":[38917807],"external_links":null,"is_released":true,"released_date":"2026-02-27T13:46:27.174035+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001624","title":"Effect of inflammation on human hematopoietic stem cells in a xenograft model","description":"Transcriptional heterogeneity in cord blood HSCs was investigated by 10X single-cell Multiome (RNA+ATAC). To investigate the effect of inflammatory stress on human HSC, 10X single-cell Multiome profiling of cells from xenografted mice recovered from repeated inflammatory challenge was performed. To investigate transmission of inflammatory stress-related molecular programs from HSC to their progeny, 10X single-cell RNA sequencing was performed on committed progenitor and myeloid cells from the same mice.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-27T13:46:30.442399+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001625","title":"PacBio HiFi Long-Read Whole-Genome Sequencing of Human Blood, Colon, and Lung Samples","description":"This dataset contains PacBio HiFi long-read whole-genome sequencing data from human blood, colon, and lung samples, including IBD and non-diseased tissues. The data enable accurate analysis of structural variants, complex genomic regions, and DNA methylation patterns, supporting genomic and epigenomic studies across tissues and disease states. High-fidelity long-read sequencing enables accurate characterization of structural variants, repetitive genomic regions, haplotype-resolved sequences, and base-level DNA methylation patterns that are challenging to detect using short-read technologies.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001626","title":"Transcriptomic analysis of photoreceptors treated with protective compounds","description":"Human retinal organoids represent a promising tool to study retinal degeneration and screen for potential compounds that prevent photoreceptor death. In this study we found a group of compounds that prevent photoreceptor degeneration in human retinal organoids. In the current dataset, we analyzed the transcriptomic changes that take place in cones and rods from organoids treated with the different saving compounds.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001627","title":"scWGS_GBM_batch1","description":"Single cell whole genome sequencing (scWGS) were used to define the clonal architecture and evolutionary trajectories of glioblastoma. By resolving genomic copy number profiles at single-cell resolution, the study aims to identify the molecular programs that sustain tumor initiation and progression, and to map how treatment reshapes the cellular ecosystem. This work provides critical insight into intratumoral heterogeneity, reveals vulnerabilities within resistant subpopulations, and supports the development of more targeted therapeutic strategies for this highly lethal cancer. (batch1, n=6 samples)","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001628","title":"Somatic Mutation Profiling of Liquid Biopsies in Enzalutamide-Treated mCRPC Patients","description":"Cell-free DNA from patients with metastatic castration-resistant prostate cancer treated with enzalutamide alone or in combination with metformin was analyzed at baseline using targeted sequencing. Somatic genomic alterations, including mutations, androgen receptor amplification, and circulating tumor DNA fraction, were assessed and correlated with clinical characteristics and outcomes to evaluate the prognostic and predictive value of liquid biopsy in the clinical setting.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001629","title":"Bulk 3' mRNA-Seq of dome and suspension tubuloids","description":"Bulk 3' mRNA-sequencing of human kidney tubuloids grown in dome and suspension culture for the identification of transcriptional differences associated with culture method, passage, and donor. Tubuloids were generated from 4 separate donors and collected for sequencing at day 7 of passage 3, 4, and 5 in dome and suspension culture.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-09T09:54:49.92992+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001630","title":"Mutational and functional heterogeneity of homology-directed repair deficiency and clinical implications","description":"Homology-directed repair (HR) deficiency is a therapeutically targetable biological state in cancer, and often considered a single, homogeneous group. By creating isogenic, highly comparable CRISPR knockouts of key HR genes, and characterizing them mutationally and functionally, we found that HRd exists along a molecular continuum and is not a single entity. Crucially, the isogenic series exposed variable penetrance of synthetic lethal interactions across genotypes. These findings argue for modernizing the molecular taxonomy of biomarkers and expanding the potential of precision-therapy opportunities - in this study alone, beyond the single label of HR deficiency. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001631","title":"Single-nucleus gene expression profiling of human fetal liver hematopoiesis (10x Multiome)","description":"The fetal liver is the primary haematopoietic organ during early human development, yet the timing and regulatory mechanisms governing blood formation remain incompletely understood. To define the cellular, transcriptional, and epigenetic changes underlying human fetal liver hematopoiesis over development, we generated a high-resolution, time-resolved single-nucleus multiome atlas of human fetal liver spanning 5–18 post-conception weeks (PCW) for CD45+CD235- cells. In total, 308,021 high-quality nuclei from 53 donors were profiled using paired chromatin accessibility and transcriptomic modalities. This study is for the gene expression.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-06T10:33:24.557684+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001632","title":"Single-nucleus chromatin accessibility profiling of human fetal liver hematopoiesis (10x Multiome)","description":"The fetal liver is the primary haematopoietic organ during early human development, yet the timing and regulatory mechanisms governing blood formation remain incompletely understood. To define the cellular, transcriptional, and epigenetic changes underlying human fetal liver hematopoiesis over development, we generated a high-resolution, time-resolved single-nucleus multiome atlas of human fetal liver spanning 5–18 post-conception weeks (PCW) for CD45+CD235- cells. In total, 308,021 high-quality nuclei from 53 donors were profiled using paired chromatin accessibility and transcriptomic modalities. This study is for the chromatin accessibility.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-06T10:33:24.557684+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001633","title":"Blood vessel depletion and immunomodulating effects of anti-VEGF therapy in metastatic clear cell renal cell carcinoma: the phase 2 A-PREDICT trial","description":"\r\nA-PREDICT is a non-randomised, open label, multicentre, phase II study of axitinib in patients with de novo metastatic ccRCC not suitable for upfront cytoreductive nephrectomy.  Patients underwent multiregional tumour sampling of primary and/or metastatic disease sites at baseline, at week 9 on treatment, at surgery (where applicable), and at disease progression. This data repository contains targetted panel sequencing performed on image-guided multi-region percutaneous biopsies of the tumour at baseline, at week 9 on treatment, at surgery (where applicable), and at disease progression.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001634","title":"Multiomic Dissection of Movement and Neurocognitive Toxicity Following BCMA-Targeting CAR T Therapy","description":"We report a case of parkinsonism following treatment with ciltacabtagene autoleucel. To investigate underlying mechanisms, we performed a multi-pronged longitudinal analysis using single-cell RNA/TCR-sequencing including both cerebrospinal fluid (CSF) and peripheral blood samples, spanning a time frame over 6 month after CAR T cell therapy.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-17T15:30:43.960362+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001635","title":"A single-cell and spatial transcriptomic atlas of multicellular remodeling in human HFpEF","description":"Heart failure with preserved ejection fraction (HFpEF) remains a major clinical unmet need, with increasing prevalence and limited therapeutic options. Despite its rising impact, the cellular and molecular mechanisms driving human HFpEF pathogenesis remain insufficiently understood, in part due to limited access to well-phenotyped myocardial tissue. Here, we leverage single-nucleus RNA sequencing (snRNA-seq) on endomyocardial biopsies from the left ventricular free wall and interventricular septum of twenty rigorously characterized HFpEF patients to generate a high-resolution, multicellular transcriptomic map of the human HFpEF heart. These data are compared to matched cardiac snRNA-seq datasets from thritytwo patients with heart failure with reduced ejection fraction (HFrEF) and eighteen non-failing donor controls, enabling a systematic investigation of disease-specific and shared transcriptional programs across left ventricular disease states. We further extend this analysis using Xenium 10x spatial transcriptomics to resolve the in situ organization of cell populations and local cellular neighborhoods in HFpEF and controls. Our analyses reveal that HFpEF cardiomyocytes exhibit a distinct electrophysiological gene-expression signature, and we identify previously unrecognized specialization within endothelial compartments, including pro-inflammatory and angiogenic signaling features that may contribute to maladaptive tissue remodeling. Machine-learning models trained on cell-type-resolved expression profiles further highlight gene determinants distinguishing HFpEF from HFrEF myocardium. Together, this study provides the most comprehensive and well-controlled single-cell atlas of human HFpEF myocardium to date, offering mechanistic molecular insights into disease pathogenesis and identifying candidate pathways for therapeutic targeting.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001636","title":"smallRNA-seq of isolated pancreatic islets (12 donors)","description":"In this study we performed smallRNA-sequencing, a sequencing method designed for small noncoding RNAs, to investigate the miRNA expression profile of human islets isolated from pancreata of donors without diabetes mellitus (n=6) and donors with type 2 diabetes (n=6).","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001637","title":"EHMT2 alterations cause a Kleefstra-like syndrome","description":"We report clinical and molecular correlates associated with six de novo EHMT2 variants identified in patients presenting with a Kleefstra syndrome–like phenotype. Transcriptomic profiling of patient-derived fibroblasts and induced pluripotent stem cells (iPSCs) reveals shared gene expression signatures between EHMT2 variant carriers and Kleefstra syndrome, compared with cell lines derived from healthy donors.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-10T08:34:39.544145+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001638","title":"IDH1 Somatic Mutation Profile in Intrahepatic Cholangiocarcinoma","description":"The objective of this study is to identify somatic IDH1 mutations in intrahepatic cholangiocarcinoma samples.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-25T10:38:17.154558+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001639","title":"Genetic Landscape of ETMR","description":"ETMRs are increasingly recognized as one of the most common, lethal infant embryonal brain tumors, driven by an oncogenic C19MC amplification. However, little is known about the ETMR genome and how it contributes to histologic and clinical heterogeneity. Herein, we performed systematic whole genome and RNA-sequencing and single cell RNA-sequencing analysis to further interrogate the ETMR genome and transcriptome.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001640","title":"Whole-genome methylation profiling of menstrual stem cells identifies novel biomarkers for endometriosis","description":"Endometriosis is a highly prevalent condition that remains underdiagnosed and poorly managed due to the lack of clinically validated biomarkers and limited understanding of its underlying pathophysiology. Although menstrual blood–derived stem cells (MenSCs) have been implicated in disease pathogenesis, their potential as a diagnostic source has not been systematically explored. We conducted a clinical study including 42 women (19 with endometriosis and 23 controls) to evaluate whether DNA methylation profiles from freshly isolated MenSCs could identify disease-specific biomarkers. Whole-genome DNA methylation sequencing identified differentially methylated regions (DMRs) enriched in genes associated with key features of endometriosis, including inflammation, tissue remodelling, and developmental processes. These DMRs robustly discriminated cases from controls, independently of technical and clinical confounders. Machine learning models trained and validated on these regions demonstrated strong diagnostic performance (specificity 83%, sensitivity 79%). Integration with an independent single-cell RNA sequencing dataset suggested that the identified DMRs may influence gene expression, supporting their biological relevance. Collectively, these findings highlight MenSC DNA methylation profiling as a promising, non-invasive strategy for early diagnosis and personalised management of endometriosis.\r\n\r\n\r\n(PubMed IDs will be provided once the manuscript is published.)","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-03T16:52:01.650043+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001641","title":"Monosomy 7 delineates a primitive acute myeloid leukemia with adverse prognosis and responsiveness to epigenetic therapy","description":"\r\nThe mechanistic basis for adverse risk associated with monosomy 7 remains undetermined in AML. In contrast to del(7q), monosomy 7 conferred adverse prognosis independent of TP53 and complex karyotype. Single-cell RNA and ATAC-seq revealed an epigenetically remodeled landscape and expansion of multipotent progenitor (MPP)-like cells. Monosomy 7 derived progenitors were distinguished by reduced chromatin accessibility and expression of STK17A and NT5C3A, which conferred resistance to cytotoxic and venetoclax-based therapy. To circumvent resistance mediated by monosomy 7 and deficient TP53, histone deacetylase inhibitors (HDACi) effectively restored apoptotic potential and augmented the activity of venetoclax. In a randomized clinical trial including older unfit patients with AML and monosomy 7, responses were observed in the majority that received low-dose cytarabine, venetoclax and the HDACi pracinostat, some with durable remissions exceeding 3 years. Longitudinal studies highlighted diminution of MPP-like cells, linking epigenetic remodeling to clinical response and therapeutic vulnerability of monosomy 7 AML.\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-13T10:27:11.211566+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001642","title":"Telomere variant sequences encode a heritable genetic blueprint for allele-specific telomere length","description":"A high-resolution workflow combining PacBio and Nanopore long-read sequencing platforms has been developed to map allele-specific telomere length in clinical patient samples. By tracing allele-specific telomeric sequence in family members across multiple generations, we show that telomeric variant sequences (TVSs) interspersed throughout the canonical repeat region are heritable (with mean similarity score > 0.95), allele-specific, and account for the extreme heterogeneity of telomere length between alleles. ","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-30T10:52:59.458219+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001643","title":"single-cell DNA and RNA from HGSOC samples using DNTR-seq.","description":"single-cell DNA and RNA from the same cells, for HGSOC samples using DNTR-seq technolgy.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-15T10:48:13.673351+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001644","title":"RTEL1 mutation as a modifier of Dyskeratosis Congenita in a family with a Telomerase RNA (hTR) template mutation and variant telomeric repeats","description":"Vertebrate telomeres, the sequences protecting the end of linear chromosomes, are composed of conserved hexameric GGTTAG repeats. Here we present a C50>A telomerase RNA template mutation that results in the incorporation of the variant telomeric repeat GTTTAG in a family with dyskeratosis congenita primarily presenting as idiopathic pulmonary fibrosis. The mutant telomerase is characterized by decreased processivity in direct telomerase activity assays and in vivo based on data from Illumina next-generation whole genome sequencing and Oxford Nanopore Technologies long-read telomere sequencing. The latter provided positional mutant repeat information that revealed the inheritance and maintenance of proximal mutant repeats in individuals who did not inherit the template mutation. Additionally, we describe an RTEL1 nonsense mutation that is associated with very short telomeres in progeny harboring wild-type telomerase and inherited mutant telomeric repeats in the absence of overt clinical phenotypes. In contrast, co-inheritance of the RTEL1 nonsense and TERC r.C50>A mutations coincided with severe early-onset DC phenotypes in two individuals.\r\n\r\n","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-02T09:33:05.116808+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001645","title":"Prenatal sodium channel dysfunction in Dravet syndrome alters cortical development ","description":"This dataset contains bulk RNA-sequencing data generated for the study “Prenatal sodium channel dysfunction in Dravet syndrome alters cortical development.” RNA-seq was performed on human cortical organoids and cortical organoid assemblies derived from induced pluripotent stem cells (iPSCs) from two individuals with Dravet syndrome and their corresponding isogenic control lines. Libraries were prepared from total/bulk mRNA and sequenced as paired-end reads. The dataset is intended to enable transcriptomic analyses of early cortical developmental changes associated with Dravet syndrome in an isogenic background.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001646","title":"Non-canonical NF-κB signaling skews B cells away from germinal center to low-affinity effector fate","description":"The non-canonical (NC) NF-κB pathway is a central regulator of B-cell development and survival, yet its role during B-cell mediated adaptive responses remains uncharted. Here, we uncover an unanticipated regulatory function for NC NF-κB in shaping humoral immunity. High-resolution mapping of NC NF-kB status in B cells from human lymphoid tissues revealed low activity in germinal center B-cells (GCB) than effector subsets, suggesting a selective attenuation. Consistently, mice model harboring B-cells with enforced NC NF-κB activation revealed near- complete loss of GCB and high-affinity antibodies, following vaccination. GCB loss was not driven by intrinsic defects in formation or expansion, but by an immune-niche dysregulation marked by regulatory T-cell expansion. Mechanistically, NC NF-κB activation promoted B-cell- derived IL-10, and blocking this axis normalize the niche and rescue GCB. Concurrently, NC NF- κB signaling boosted low-affinity antibody responses by transcriptionally priming follicular B- cells for plasmacytic differentiation. Together, these findings position NC NF-κB as a tunable rheostat linking B-cell signaling to immune-niche control and humoral immunity.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-05T12:08:58.736733+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001647","title":"ONT and PacBio data of 22q11 patient-parent duos/trios","description":"ONT and PacBio FASTQ files generated for de novo assembly and resulting de novo assemblies","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-09T11:27:23.969468+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001648","title":"Integrated analysis of targeted DNAseq and RNAseq on peripheral blood mononuclear cells (PBMC) of hip replacement surgery patients","description":"Patient samples were collected from individuals undergoing elective femoral head replacement surgery. Eligible participants were aged >50 years, classified as otherwise healthy, and able to provide written informed consent. Exclusion criteria were trauma-related femoral hip replacement and any known hematological malignancy. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-28T13:56:15.975481+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001649","title":"Integrated Single-Fiber Multi-Omics in ICU-acquired weakness","description":"To directly connect disease-associated molecular states to the contractile machinery, this study combined sequential functional, transcriptomic, and proteomic profiling of the same single human rectus femoris myofibers from critically ill patients in the intensive care unit with acquired weakness (ICU-AW) and controls. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-20T15:23:52.605052+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001650","title":"RBMX functional retrocopy safeguards brain development","description":"Retrotransposition has generated thousands of intronless gene copies in mammalian genomes, yet their contribution to brain development and evolution remains largely unexplored. We investigated the role for RBMX retrocopy in shaping neurodevelopment and modulating disease. First, we reported 8 distinct pathogenic variants in RBMX, an X-linked splicing regulator, in 11 males presenting with intellectual disability, microcephaly, and cortical malformations. Then, we combined transcriptomic profiling, protein–protein and protein–RNA interaction studies both in human cellular models and mouse embryonic cortices to assess the functional redundancy between RBMX and its retrocopy RBMXL1. Finally, we use mouse genetics to dissect RBMX function and its compensation by RBMXL1 in corticogenesis. We show that RBMX pathogenic variants disrupt cortical development through both loss- and gain-of-function mechanisms. Surprisingly, despite severe phenotypes in humans, Rbmx-deficient mice display only mild cortical abnormalities, a discrepancy likely due to compensation by Rbmxl1, a retrocopy that arose independently in mice and humans. We demonstrate that RBMX and RBMXL1 share protein and RNA partners and act redundantly in brain development, with RBMXL1 buffering the impact of RBMX deficiency. Together, these findings establish that RBMXL1 functions as a functional paralog of RBMX safeguarding neurodevelopment by buffering deleterious variation. More broadly, these results identify retrocopies as active contributors to neurodevelopmental robustness and suggest that functional retrocopies may have facilitated the evolutionary diversification of the mammalian brain.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-12T15:34:15.194423+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001651","title":"ScDNAseq in pediatric UBA1-mutated MDS","description":"This study investigates clonal architecture in the first pediatric MDS case with somatic UBA1 mutation, and tracks clonal dynamics during CPX-351 therapy. Single-cell DNA and Protein libraries from bone marrow mononuclear cells from Diagnosis and post-CPX-351 cycle #1 were sequenced on Illumina platforms and analyzed on the Tapestri pipeline.","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-07T10:27:15.30256+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001652","title":"PXA study","description":"Pleomorphic xanthoastrocytomas (PXAs) are rare glial tumors of adolescents and young adults that commonly harbor BRAFV600E mutations with concurrent CDKN2A/B loss. Despite multi-modal therapies, survival remains poor. We assembled one of the largest PXA cohorts to date with long-term follow-up, including matched primary and relapse samples, to investigate malignant evolution and the tumor microenvironment. Multi-omic analyses integrating bulk and single-cell profiling, spatial transcriptomics, and proteomics provided a comprehensive view of PXA biology and immune dynamics across recurrences. The genomic landscape was largely stable, with variable mutational burden unrelated to outcome. Transcriptional profiling revealed two major tumor populations: an immature, SOX9+ astrocytic population associated with sparse microglia, and a fibroblast-like population enriched in immune cells, dominated by exhausted T cells and immunosuppressive macrophages, yet notably depleted of microglia. These are unique features among brain tumors. Immune enrichment in fibroblast-like regions correlated with CXCL12 expression and recruitment of CXCR4⁺ immune cells, whereas SOX9-positive astrocytic regions expressed CXCL14, an inhibitor of the CXCL12–CXCR4 axis, driving immune exclusion. Longitudinal analyses showed that dominance of SOX9+ astrocyte-like cells and loss of T cells predicted aggressive, fatal progression. Our data suggest that PXAs arise from CXCL12-expressing meningeal fibroblasts, where oncogenic BRAF signaling, facilitated by concurrent CDKN2A/B loss, induces SOX2, SOX9, and NFIB expression, reprogramming these cells into highly invasive, CXCL14-expressing, immature astrocytes, which drive immune depletion and poor outcome. Together, these findings define the cellular and immune context of PXA, identify prognostic biomarkers, and uncover therapeutic vulnerabilities. ","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-19T15:40:50.161722+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001653","title":"TenK10K Phase 1:  Single Cell","description":"Understanding the genetic basis of gene expression can shed light on the regulatory mechanisms underlying complex traits and diseases. Single-cell resolved measures of RNA levels and single-cell expression quantitative trait loci (sc-eQTLs) have revealed genetic regulation that drives sub-tissue cell states and types across diverse human tissues. Here, we describe the first phase of TenK10K, the largest- to-date dataset of matched whole-genome sequencing (WGS) and single-cell RNA-sequencing (scRNA-seq). We leverage scRNA-seq data from over 5 million cells across 28 immune cell types and matched WGS from 1,925 individuals. This provides power to detect associations between rare and low-frequency genetic variants that have largely been uncharacterised in their impact on cell-specific gene expression. We map the effects of both common and rare variants in a cell type specific manner using SAIGE-QTL.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-27T14:10:50.961851+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001654","title":"Tenk10k Phase 1: Genotypes","description":"TenK10K Phase 1 is a dataset of matched human whole-genome sequencing (WGS) from 1,925 individuals, and single-cell RNA sequencing (scRNA-seq) from over 5 million peripheral blood mononuclear cells across 28 immune cell types. Single-cell ATAC sequencing was additionally performed on a subset of 922 individuals. This EGA study consists of the WGS data from 1,925 individuals while a separate EGA study comprises the scRNA-seq and scATAC-seq data.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-02-27T14:10:44.740274+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001655","title":"Immune cell atlas of environmental and ancestral diversity in Indonesia [WGS]","description":"Island Southeast Asia (ISEA) remains consistently underrepresented in large-scale human genomic resources despite its rich ancestral and lifestyle diversity. The region's complex population history and environmental/pathogen pressures could have shaped its populations' unique immune responses. Here, we generated single-cell PBMC profiles from 199 Indonesians sampled across four populations in the islands of Bali and New Guinea. The dataset consists of low-pass whole genome sequencing and pooled single-cell PBMC transcriptome sequencing, including T-cell receptor (TCR). These groups capture diversity in regional genetic ancestries (West ISEA-like and Papuan-like) and lifestyle contrasts (urban versus rural communities in Bali; highland versus lowland communities in New Guinea), providing a window into how ancestry and environment jointly shape immune variation across ISEA. Together, this study provides the first large-scale single-cell immune atlas of ISEA, highlighting how ancestral and environmental diversity jointly shape human immunity in this globally important yet understudied region.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-07T17:39:47.669389+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001656","title":"Immune cell atlas of environmental and ancestral diversity in Indonesia [scRNAseq]","description":"Island Southeast Asia (ISEA) remains consistently underrepresented in large-scale human genomic resources despite its rich ancestral and lifestyle diversity. The region's complex population history and environmental/pathogen pressures could have shaped its populations' unique immune responses. Here, we generated single-cell PBMC profiles from 199 Indonesians sampled across four populations in the islands of Bali and New Guinea. The dataset consists of low-pass whole genome sequencing and pooled single-cell PBMC transcriptome sequencing. These groups capture diversity in regional genetic ancestries (West ISEA-like and Papuan-like) and lifestyle contrasts (urban versus rural communities in Bali; highland versus lowland communities in New Guinea), providing a window into how ancestry and environment jointly shape immune variation across ISEA. Together, this study provides the first large-scale single-cell immune atlas of ISEA, highlighting how ancestral and environmental diversity jointly shape human immunity in this globally important yet understudied region.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-07T17:39:44.585817+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001657","title":"Whole Genome Sequencing of cell-free-DNA in High-Risk Smoldering Multiple Myeloma ","description":"In this study, we used 40x whole-genome sequencing of plasma cfDNA from high risk smoldering multiple myeloma patients (HR-SMM) to assess minimal residual disease (MRD) status. We generated 87 BAM files from patients at baseline, at progression or MRD conversion, and 3- and 6- months before progression or MRD conversion. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001658","title":"Stimulation of healthy donor NK cells with IL-15, TGF-β, and tumor cells for 6 days to induce a taNK phenotype.","description":"To generate sufficient number of taNK cells for functional assays, we established an in vitro model mimicking the taNK phenotype. Bulk RNA sequencing validated the phenotype by comparing CD103⁺CD49a⁺ (ta)NK cells to CD103⁻CD49a⁻ non-taNK cells.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-10T11:04:19.536924+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001659","title":"BEXMET: A Phase I Trial Exploring the Role of Bexarotene in Inducing Chemotherapy Susceptibility in Metastatic TNBC","description":"The ability to precisely manipulate cancer cell states represents a promising approach to enhance therapeutic response. Our previous work demonstrated that retinoids can reduce tumorigenicity in triple-negative breast cancer (TNBC) models by shifting cells from a mesenchymal to an epithelial state, thereby sensitizing resistant TNBC cells to standard-of-care treatments. Here, we designed a Phase I trial, BEXMET, to investigate whether bexarotene, a retinoid X receptor agonist, can induce epithelial cell state changes and increase sensitivity to capecitabine in patients with metastatic TNBC. This cohort included 12 patients who received bexarotene during a two-week lead-in period, followed by repeated treatment cycles consisting of two weeks of oral capecitabine and one week of bexarotene. Tumor biopsies were collected at four timepoints: pre-treatment, post-bexarotene lead-in, post-capecitabine (cycle 1), and at disease progression (if applicable). RNA-Seq and multiplex immunohistochemistry were performed on all biopsies. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001660","title":"An autoinflammatory RIG-I variant causing Singleton-Merten Syndrome associates with small non-coding Y-RNAs","description":"The RNA sensor RIG-I performs a critical role in surveying the cytoplasm for the presence of viral nucleic acids and initiating the downstream anti-viral type I interferon pathway. Through recognition of specific features, such as the presence of a 5’ di/triphosphate motif or highly structured base-paired regions, RIG-I effectively differentiates between RNA of viral- and self-origin. In Singleton-Merten syndrome (SMS), gain-of-function variants in RIG-I lead to a breakdown in this surveillance system and results in aberrant sensing of self-RNAs and deleterious upregulation of type I interferons. The identity of the self-RNAs binding to gain-of-function RIG-I mutants has remained elusive and would provide a greater understanding of the aetiology of SMS. Here we used an infrared individual-nucleotide resolution UV-crosslinking and immunoprecipitation (irCLIP) approach to determine the RNA profile bound to a previously characterised ATPase-deficient SMS variant, RIG-IC268F. irCLIP identified a broad array of self-RNAs, primarily those transcribed by RNA polymerase III, that were bound to RIG-I. Subsequent native RNA immunoprecipitation confirmed a prominent and specific interaction between RIG-IC268F and Y-RNAs, a family of four structurally similar non-coding RNAs. Manipulation of Y-RNAs alone by targeting either Y-RNA transcripts or Y-RNA stabilising proteins was insufficient to negate RIG-I induce interferon, hinting at a broader profile of RNA polymerase III-derived RNAs being influential in driving the sterile activation of gain-of-function RIG-I variants.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-20T10:27:08.548404+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001661","title":"VariantMedium: Sensitive and generalizable somatic point mutation calling with 3D DenseNets trained and evaluated on experimental confirmation data","description":"This study contains whole-exome sequencing (WES) and results of targeted deep-sequencing data of three matched tumor and normal cell lines, with two technical WES replicates each. The calls by Mutect2, Strelka2, and VariantMedium  were confirmed using targeted deep sequencing on Illumina Miseq The targeted deep sequencing was performed in three runs and the results are summarized under VCF files.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-13T13:24:54.476013+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001662","title":"Human PMS1-dependent non-canonical mismatch repair converges with MBD4 to repair 5-methylcytosine deamination","description":"CpG dinucleotides are mutational hotspots due to spontaneous deamination of 5-methylcytosine (5mC), resulting in T:G mismatches that can lead to CpG>TpG transitions. These mutations are a hallmark of aging and cancer and play a central role in the evolution of vertebrate genomes. We have previously uncovered MBD4 as the primary Base Excision Repair (BER) glycosylase responsible for 5mC deamination repair. Here, we employ an APOBEC1 deaminase fused to a catalytically dead Cas9 to induce targeted 5mC deamination independently of DNA replication, and track its repair in human cells. This approach reveals that MBD4 elicits a coordinated repair response with a non-canonical branch of Mismatch Repair (MMR) involving complexes MutLβ (MLH1-PMS1) and MutSα (MSH2-MSH6). We demonstrate that human PMS1 loss phenocopies the CpG>TpG hypermutation associated with MBD4 deficiency, revealing 5mC deamination repair as one of its main functions. Structural predictions with functional validation reveal that MBD4 activity is dependent on its physical interaction with MutLβ. In alignment with our experimental data, we show that the CpG>TpG mutational burden of MMR-deficient tumors is partly explained by replication-independent processes. Altogether, we uncover a novel function of non-canonical MMR that underscores its interplay with BER in safeguarding genomic integrity against damage to methylated DNA.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-17T15:48:18.690922+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001663","title":"Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer: exploratory biomarker analyses from CheckMate 577","description":"Adjuvant nivolumab demonstrated a significant improvement in disease-free survival (DFS; primary endpoint) versus placebo in patients with resected esophageal or gastroesophageal junction cancer and residual pathologic disease following neoadjuvant chemoradiotherapy (CRT) in the phase III CheckMate 577 study, leading to global approval and widespread adoption. Exploratory biomarker analyses were performed using whole-exome sequencing, RNA sequencing, and immunohistochemistry. Hazard ratios for DFS favored nivolumab versus placebo in patients with higher inflammation and proliferation gene expression signature scores; lower M2 macrophage, endothelial, and stromal GES scores; and higher densities of CD3+/CD8- T cells and natural killer cells. Assessments of pre-CRT and post-CRT tumor tissue found post-CRT increases in programmed death ligand 1 combined positive score in 51% of patients, which appeared to be associated with greater DFS benefit. Through these analyses, we identified patient subpopulations that appear to derive improved DFS benefit from adjuvant nivolumab in this setting.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-09T10:27:56.689191+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001664","title":"Indigenous American Diversity and Evolution","description":"The Indigenous American Genomic Diversity Project (IAGDP) investigates the genomic diversity and evolutionary history of Native American populations, which remain underrepresented in global genomic research. As part of this effort, we generated high-coverage whole-genome sequences individuals sampled across eight Latin American countries. This study provides a resource for investigating population structure, demographic history, and adaptive evolution in Indigenous American populations.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-09T09:56:41.692056+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001665","title":"Case Report: Pre-Clinical Combination Targeting VEGF and PI3K in a Rare, Aggressive Mixed Endometrial Carcinoma","description":"We report a rare case of a young patient (VENUS 167) initially diagnosed with grade 1 endometrioid endometrial cancer, which, following endocrine treatment, presented with mixed aggressive carcinoma with three distinct histologic patterns: grade 1 endometrioid, large cell neuroendocrine, and undifferentiated carcinoma. The surgical specimen at the time of disease progression was used to establish OPTO.85, a patient-derived organoid (PDO), followed by a corresponding organoid-derived xenograft (ODX). Multi-omic analyses confirmed that OPTO.85 accurately reflected the patient’s tumor characteristics. WES analysis identified oncogenic alterations in PIK3CA, ARID1A, and CTNNB1. Further RNA-seq and ATAC-seq analyses revealed enrichment in VEGF and Wnt signaling pathways, suggesting therapeutic vulnerabilities. A high-throughput drug screen was conducted using ApexBio-Approved and Epigenetic Drug Libraries, along with Kinase Inhibitor and Tool Compound Libraries developed at the Ontario Institute of Cancer Research. The OPTO.85 PDO exhibited sensitivity to PI3K inhibitors and responsiveness to VEGF inhibition. Cediranib demonstrated synergy with BKM120, significantly reducing organoid growth. This combination also showed in vivo efficacy in the ODX model, where dual inhibitors significantly suppressed tumor growth compared to single compounds. This case exemplifies the impact of genomic profiling and patient-derived models in identifying actionable molecular changes in rare cancers with limited therapeutic options and poor prognosis. It highlights that high-throughput sequencing for individual patient tumors and generation of patient-derived models are feasible in endometrial cancer. This preclinical model may assist clinical decision and personalized therapy requiring validation in prospective studies.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-20T08:23:55.419918+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001666","title":"Long-read sequencing of saliva collected and stablized at room temperature in Oragene devices on the PacBio Revio","description":"Saliva collected in Oragene™ devices and extracted with Nanobind kits yields high‑molecular‑weight DNA suitable for PacBio HiFi whole‑genome sequencing, offering a convenient alternative to blood collection (“High-quality HMW DNA was obtained from all samples…”). Sequencing of paired saliva and blood samples on the Revio system produced comparable HiFi read lengths, yields, and 30–39× genome coverage. Methylation profiles were also highly similar, with minor differences attributable to small amounts of non‑human DNA present in saliva (“DNA extracted from saliva is typically ~75–95% human…”). Variant calling using PacBio WGS pipelines showed high concordance between saliva and blood from the same donor for both SNVs and structural variants. These results demonstrate that saliva enables reliable, high‑throughput HiFi sequencing workflows with performance equivalent to blood.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-19T17:32:14.503959+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001667","title":"RNA-Sequencing of LCL cells","description":"LCL cells with BAP1 variants are grown and harvested for their RNA. RNA-sequencing was performed to determine the difference between different BAP1 variants. 2 biological replicates were performed.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001668","title":"scNMT sequencing to support multimodal reference atlas of the human kidney","description":"The study aimed to generate paired single‑cell nucleosome, DNA methylation, and transcription (scNMT) data for major human kidney cell types. Using the scNMT protocol, genomic DNA and RNA was captured from the same cells, with SMART‑seq2 enabling comprehensive transcriptome profiling across the kidney. For selected proximal and distal tubule populations, the genomic DNA underwent bisulfite sequencing to assess CpG methylation patterns in promoters and gene bodies, while GpC methylation provided measurements of chromatin accessibility. Together, these measurements support the development of a multimodal reference atlas of kidney cell types.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001669","title":"Genomic and transcriptomic profiling of colorectal cancer patient-derived organoids","description":"This study describes controlled-access human sequencing data generated from colorectal cancer patient-derived organoids established using the CTOS method. Whole-exome sequencing (WES) and RNA sequencing (RNA-seq) were performed to characterize genomic alterations and transcriptomic profiles of the organoids.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-30T17:46:14.887317+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001670","title":"snRNA-seq data from a phase 2 trial of dasatinib for patients with relapsed or refractory nodal T follicular helper cell lymphomas","description":"snRNA-seq data from tumor tissue samples of 4 patients enrolled in a phase 2 trial of dasatinib for relapsed or refractory nodal T follicular helper cell lymphomas.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-16T10:54:24.5418+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001671","title":"Multiple sclerosis iPSC derived-pericytes contract poorly but respond robustly to lesion-relevant environmental stimuli","description":"iPSC-derived pericytes were generated from people with multiple sclerosis, and people who do not have multiple sclerosis. iPSC-derived pericytes were exposed to myelin debris, hypoxia and/or inflammatory conditions to simulate a multiple sclerosis lesion-like environment. Transcriptome sequencing was undertaken of experimental conditions to identify iPSC-dervied pericyte responses to multiple sclerosis lesion-like environment. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001672","title":"Transcriptome analysis of soft tissue sarcoma","description":"We characterized mRNA expression profile of soft tissue sarcomas.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-10T12:06:00.697975+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001673","title":"Whole exome sequencing of soft tissue sarcoma","description":"We characterized genomic alterations of soft tissue sarcoma.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-10T12:06:00.697975+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001674","title":"Transcriptomic landscape of C1498 cells","description":"We characterized the mutations and gene fusion events (at RNA level) of C1498 cells by whole transcriptome sequencing analysis.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-27T12:45:40.974992+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001675","title":"Circulating cell-free DNA methylation profiling for detection, distinction, and estrogen receptor status classification of advanced breast cancer","description":"We developed cell-free DNA (cfDNA) methylation signatures for minimally invasive breast cancer detection, distinction, and estrogen receptor (ER) status classification with cell-free Methylated DNA Immunoprecipitation and Sequencing (cfMeDIP-seq). We profiled peripheral blood plasma from 87 patients with mBC spanning ER-positive/HER2-negative (ER+/HER2-), HER2-positive, and triple-negative breast cancer (TNBC).","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-30T10:40:50.648462+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001676","title":"Mutational and functional heterogeneity of homology-directed repair deficiency and clinical implications","description":"Homology-directed repair (HR) deficiency is a therapeutically targetable biological state in cancer, and often considered a single, homogeneous group. By creating isogenic, highly comparable CRISPR knockouts of key HR genes, and characterizing them mutationally and functionally, we found that HRd exists along a molecular continuum and is not a single entity. Crucially, the isogenic series exposed variable penetrance of synthetic lethal interactions across genotypes. These findings argue for modernizing the molecular taxonomy of biomarkers and expanding the potential of precision-therapy opportunities - in this study alone, beyond the single label of HR deficiency.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001677","title":"BCG-Flu_Challenge_Study_RNAseq_Human_01","description":"RNA sequencing data generated from human samples collected in the BCG-Flu Challenge study.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-13T10:05:32.532882+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001678","title":"Kbtbd13 knock-down restores muscle function in a human-based mouse model of nemaline myopathy type 6","description":"Nemaline myopathy type 6 (NEM6) is caused by pathogenic variants in KBTBD13. Patients experience muscle weakness, excessive fatigue and impaired muscle relaxation which significantly impact their daily activities. NEM6 pathophysiology consist of abnormal protein aggregation in muscle cells and a predominance of slow-twitch myofibers, and most patients carry the Dutch founder variant in KBTBD13 (NP_001094832.1: p.Arg408Cys, referred to as KBTBD13R408C). Currently, no specific therapy is available. Here, we used a KBTBD13R408C knock-in mouse model and aimed to identify the molecular changes driving disease pathogenesis and to define a therapeutic window to test a therapeutic intervention. We revealed that the mouse model closely phenocopies the human phenotype at a morphological, functional, and transcriptional level and that the p.Arg408Cys variant causes mis-localization of KBTBD13 within the muscle sarcomere. Our natural history data in the Kbtbd13(R408C) mouse model showed that disease onset occurs between 1-3 months and plateaus by 9 months with little progression at 18 months.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-20T10:26:36.51351+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001679","title":"ICARUS-LUNG01-GEOMx","description":"A GeoMx spatial transcriptomic study using 7 patients from the ICARUS LUNG01 trial focusing on tumour and immune cell compartments. We selected 7 paired baseline and on-treatment patient samples for analysis. We selected up to 4 regions of interest (ROI) per sample tissue. We identified tumour and immune cell areas of illumination (AOI) using CK and CD45 antibodies respectively","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-12T07:51:00.814329+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001680","title":"1000 Myelodysplastic Neoplasm Exomes","description":"Whole-exome sequencing data from bone marrow-derived mononuclear cells from 1,009 patients with myelodysplastic neoplasm (MDS)","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001681","title":"Single-cell whole-genome sequencing reveals convergent evolution in Burkitt lymphoma","description":"This depository contains the raw BAM/CRAM files used in the manuscript \"Single-cell whole-genome sequencing reveals convergent evolution in Burkitt lymphoma\" Steemers et al. (2026). \r\n\r\nThis includes:\r\n- 332 PTA-based single-cell WGS samples (~15X depth)\r\n- 7 bulk tumour samples (~30X depth) with matched germline samples (~30X depth)\r\n- 14 bulk tumour samples seqeunced by the Princess Maxima Centre diagnostics department (~105X depth) with matched germline samples (~35X depth)","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-22T14:54:32.70635+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001682","title":"Multimodal analysis of rare BARD1 missense variant","description":"This project analyzes whole-exome sequencing data from a patient with breast cancer recurrence and endometrial cancer, as well as from the patient’s father’s colon tumor, all harboring a rare germline BARD1 missense variant (p.Gly753Val). The data reveal loss of heterozygosity and homologous recombination deficiency specific to the triple-negative breast cancer recurrence, supporting the variant’s conditional pathogenicity linked to prior treatment.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-16T16:52:05.791865+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001683","title":"Bulk RNA Sequencing of MTAP-Deficient and MTAP-Proficient Pulmonary Carcinoids","description":"Transcriptomic profiling was performed on 6 fresh-frozen pulmonary carcinoid samples, including 3 MTAP-proficient cases (P1, P2, P3) and 3 MTAP-deficient cases (P8, P10, P12), to conduct differential gene expression analysis and validate MTAP status at the mRNA level.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001684","title":"Whole exome sequencing from MTAP-Deficient and MTAP-Proficient Pulmonary Carcinoids","description":"Whole Exome Sequencing (WES) was performed on DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues from 12 pulmonary carcinoid tumors and their matched non-tumor tissues (24 samples in total) to identify somatic mutations and copy number variations (CNVs). Among the tumor samples, 7 were MTAP-proficient (P1–P7) and 5 were MTAP-deficient (P8–P13).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001685","title":"GERAS - Genome Wide Analysis of Epigenetic Changes in Aging (Methylation)","description":"Aging is associated with epigenetic modifications. In this study, we performed whole genome bisulfite sequencing (WGBS) analysis of human blood samples of male and female donors of different ages. Based on this, we investigate DNA methylation profiles.\r\n","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001686","title":"Impact of Mutated CTCF DNA binding sites of Topologically associating domains on nearby Cancer Gene Regulation: A Multi-Omics Analysis","description":"Cutaneous squamous cell carcinoma (cSCC) is the most common lethal malignancy world-wide. Due in most part to the extremely high mutational burden (TMB) in cSCC, making sense of it’s non-coding and regulatory regional genomic variation has lagged that of other far less common cancers. This study presents the first investigation of mutations at CCCTC-binding factor binding sites (CTCFbs) of Topologically associating domains (TAD) across defined cSCC progression stages—primary non-metastatic (PNM), primary metastat-ic (PM), and lymph node metastasis (LNM).","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[35982973],"external_links":null,"is_released":true,"released_date":"2026-08-10T16:15:45.881974+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001687","title":"scWGS of tumors resected from GBM patients at diagnosis and relapse (batch2, n=6 samples)","description":"Single cell whole genome sequencing (scWGS) were used to define the clonal architecture and evolutionary trajectories of glioblastoma. By resolving genomic copy number profiles at single-cell resolution, the study aims to identify the molecular programs that sustain tumor initiation and progression, and to map how treatment reshapes the cellular ecosystem. This work provides critical insight into intratumoral heterogeneity, reveals vulnerabilities within resistant subpopulations, and supports the development of more targeted therapeutic strategies for this highly lethal cancer. (batch2, n=6 samples)","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001688","title":"Global RNA sequencing data of human iPSC-derived microglia from frontotemporal dementia (FTD) patients","description":"Global RNA sequencing was performed in RNA samples extracted from human iPSC-derived microglia from healthy controls and sporadic (non-genetic) and genetic C9orf72 hexanucleotide repeat expansion-carrying patients with FTD.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-10T14:14:26.660358+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001689","title":"Long-read whole-genome sequencing of post-mortem sporadic PD cases and non-PD controls using gut tissue","description":"This study aims to enable in-depth genomic characterization of Parkinson’s disease (PD) by examining single nucleotide polymorphisms, structural variants, and quantitative trait loci. Long-read whole-genome sequencing was performed using the Oxford Nanopore PromethION platform on colon tissue collected post‑mortem from PD patients and non-PD controls. These data contribute high-resolution insights into genomic variation that may affect PD biology. The project is part of Team Voet’s efforts within the ASAP Collaborative Research Network, which promotes resource sharing and accelerates discovery in Parkinson’s disease research.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-08T13:03:24.252416+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001690","title":"Whole genome sequencing  data of paediatric hyperdiploid acute lymphoblastic leukemia","description":"The hyperdiploid (HeH) subtype with 51–67 chromosomes is the most common subtype in childhood, presented in 25–30% of the cases, and is associated with excellent prognosis . The HeH subtype harbors relatively few additional genetic alterations, suggesting that extra chromosomes are the driving event for leukemia onset. Secondary hits usually affect the RAS signaling pathway and histone modifiers.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-23T11:25:46.824763+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001691","title":"Integrating transcriptional regulatory networks with chromatin accessibility as markers of survival outcome and drug response in triple-negative breast cancer ","description":"Patients with triple-negative breast cancer (TNBC), a highly aggressive and heterogeneous breast cancer subtype, have limited effective targeted therapy options and frequently develop resistance to chemotherapy. Transcription regulators (TRs) guided precision medicine, namely anti-estrogen receptor therapy, has proven successful in hormone-dependent breast cancer, but remains a challenge in TNBC. Here, we identified key TRs underlying TNBC identity by combining a transcriptional interaction network with chromatin accessibility and defined TR activity score metrics. We show that the activity scores of these TRs independently discriminate patient outcome across different clinical endpoints. Matching TR activity scores to drug sensitivity identified drug-TR pairs across independent datasets, including NFE2L3 and CBFB activity associated with sensitivity to mTOR inhibition, which we validated using a cohort of TNBC patient-derived xenografts. Collectively, we present methodology to promote TR-guided precision medicine that captures inter-tumor heterogeneity in TNBC and nominates drug sensitivities according to TR activity scores inferred from expression and chromatin accessibility data.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-25T12:54:12.957024+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001692","title":"Human microglial transitions at the Aβ–Tau inflection point associate with divergent pathways to dementia and resilience","description":"Alzheimer's disease depends not just on plaques and tangles, but on how brain cells respond to them. Using spatial and single-cell genomics across cognitively impaired octogenarians, healthy octogenarians, and cognitively intact centenarians with similar amyloid levels, we identified six spatial tissue states forming a disease continuum with a critical transition point where amyloid-driven inflammation gives way to tau-linked cellular programs. Microglia drive this shift, progressing from early inflammatory to late antigen-presenting states — and resilient individuals diverged here: healthy octogenarians never activated the late microglial program, while centenarians did so without the expected tau accumulation. This positions microglial state transitions at the amyloid-to-tau boundary as key targets for understanding and promoting resilience to Alzheimer's disease.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-08T11:06:16.484846+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001693","title":"ABO: a 3D stroma-supported culture platform enabling full human B lymphopoiesis for disease modeling and gene therapy development","description":"Defective B-cell development underlies a large proportion of inborn errors of immunity, but progress in understanding disease mechanisms and of developing therapies has been limited by inadequate human in vitro models. Here, we establish a 3D aggregate culture platform composed of hematopoietic stem and progenitor cells (HSPCs) and mouse bone marrow stromal cells as an assay for efficient B-cell output (the ABO platform). ABOs supported progression through pro-B, pre-B, immature, and transitional B-cell stages, with a transcriptional profile and B-cell receptor (BCR) repertoire diversity closely resembling human bone marrow B-cell ontogeny. ABO-derived B cells exhibited functional signaling and differentiated into class-switched memory and antibody-secreting B cells following CD40-mediated stimulation. The ABO platform reproduced the arrest in B-cell development observed in RAG1-SCID patient–derived HSPCs, which was corrected by lentiviral RAG1 gene therapy. Thus, ABOs provide a clinically relevant platform for modeling B-cell immunodeficiencies and evaluating therapeutic strategies.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-24T10:29:14.873388+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001694","title":"Tumorigenic DICER1 mutations rewire miRNA circuitry to stabilize pro-growth mRNAs and degrade pro-apoptotic mRNAs ","description":"DICER1 plays a central role in microRNA (miRNA) biogenesis, using its RNase IIIa and RNase IIIb domains to cleave pre-miRNA stem-loops and generate mature 3′-arm (3p) and 5′-arm (5p) miRNAs, respectively. Importantly, specific DICER1 missense variants that disrupt RNase IIIb activity are pathogenic and implicated in tumorigenesis. Here, we examined the effects of two pathogenic DICER1 variants: the canonical RNase IIIb mutant E1813K and the non-canonical RNase IIIa mutant S1344L, the latter of which impairs RNase IIIb activity by disrupting its catalytic pocket. Strikingly, while both variants impair 5p miRNA production and enhance 3p miRNA levels, S1344L impairs only a subset of 5p miRNAs. Consistent with their differential effects on 5p miRNA production, E1813K and S1344L induce only partially overlapping gene expression changes relative to wild-type DICER1 cells. Comparison with a DICER1 mutant–initiated pituitary blastoma further identified a discrete set of mRNAs that are stabilized and increased in abundance, many of which promote cell proliferation. Conversely, several mRNAs encoding pro-apoptotic factors exhibit reduced stability. Together, these findings suggest that tumor promoting DICER1 mutants reprogram mRNA stability to promote proliferation while suppressing apoptosis. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001695","title":"Phenotypic and Functional Changes During Culturing of Adipose-Derived Primary Cells","description":"Primary human adipose stem and progenitor cells (ASPCs) are widely used to investigate adipocyte biology and mechanisms underlying metabolic disease, yet the extent to which these in vitro models retain their in vivo identity remains insufficiently understood. In this study, we examined how short term culture expansion influences ASPC phenotype and functional potential. Using single cell flow cytometry and bulk RNA sequencing, we demonstrate that ASPCs derived from the stromal vascular fraction undergo a marked shift in cellular identity between day 1 (D1) and day 7 (D7) after plating, expressing a mesenchymal stromal cell (MSC)-like enriched signature at D7. In differentiated cells, the identity shifts between D1 and D7 corresponded to differences in adipogenic differentiation capacity, indicating that even brief in vitro expansion can influence experimental outcomes.\r\nOur findings highlight that cultured ASPCs do not represent a static population but instead undergo compositional drift that may obscure or confound interpretations of adipocyte development and metabolic responsiveness. These results underscore the importance of considering culture induced changes when using primary adipose models to study adipogenesis, depot specific biology, or disease relevant phenotypes. Future work incorporating single cell transcriptomics, functional assays of defined subpopulations, and alternative culture systems will be essential for determining how closely ex vivo ASPCs mirror their in tissue counterparts and for improving the translational relevance of adipose cell culture models.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001696","title":"Development and first-in-human CAR T therapy targeting the pathognomonic MiT-fusion driven protein GPNMB","description":"Summary: CAR T therapy for solid tumors is constrained by the scarcity of safe, uniformly expressed cell-surface targets. Here we identify GPNMB, a MiT fusion-driven protein, as highly, homogeneously, and stably expressed in primary and relapsed translocation-positive alveolar soft part sarcoma (ASPS) and renal cell carcinoma (tRCC). We develop a GPNMB-directed CAR T cell product, GCAR1, which demonstrates potent activity against patient-matched cells, organoids and xenograft models. In a first-in-human treatment of two patients with relapsed/refractory, metastatic ASPS, GCAR1 is well tolerated and induces stable disease for up to 6 months, accompanied by resolution of many non-target lesions. GCAR1 T cells expand in peripheral blood as a polyclonal population and remain detectable for up to 6 months. Spatial transcriptomics identify multiple immunosuppressive niches adjacent to T cells infiltrating treatment-resistant lesions; biological PDL1 blockade or PD1 and TIGIT double knockout overcomes this resistance and shows synergistic activity with GCAR1 in xenograft models. Taken together, these data provide clinical proof-of-concept for treating solid tumors with CAR T cells targeting a surface antigen driven by an oncogenic gene fusion.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-08T14:24:23.729788+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001697","title":"A reference atlas of human fetal membranes from mid-gestation to term","description":"Human fetal membranes are barrier to shield the developing fetus from mechanical, immune and infection-related insults and therefore essential to sustain pregnancy. While their dysfunction results in preterm prelabor rupture of membranes (PPROM), limited knowledge about changes in their characteristics during development is currently available. Here, we present a single-nucleus RNA sequencing atlas of reflected amnion and chorion from midterm to term gestation, and we relate these to samples derived from preeclampsia and the immediate vicinity of placenta. Key findings include a broad downregulation of heat shock proteins besides the upregulation of pappalysins and the downregulation of insulin-like growth factor binding proteins, likely resulting in the increased availability of insulin-like growth factor (IGF-2) at term. Additionally, changes in extracellular matrix composition, reduction of canonical wingless/integrated (WNT) signaling, and diminished epithelial plasticity were observed. Cell–cell communication analyses revealed progressive immune remodeling, with maternal macrophages and natural killer cells shaping the signaling environment of the fetal membrane. While integration with first-trimester data demonstrates continuity of developmental programs, preeclampsia samples showed dysregulated maternal cells. This atlas provides a high-resolution reference for fetal membrane biology, offering insights into regulatory mechanisms underlying pregnancy maintenance, PPROM, and related complications.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-14T16:15:38.129339+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001698","title":"Ensilication as a Cold‑Chain–Free Solution for High‑Fidelity DNA Preservation in tumor samples","description":"Nucleic acid preservation requires continuous refrigeration at -20 °C to -80 °C, creating infrastructure barriers limiting genomic medicine access globally. While ambient-temperature preservation methods exist, their effects on DNA integrity and sequence fidelity remain incompletely characterized. The project aims to evaluate ensilication as a method for preserving DNA at ambient temperatures and to determine whether it can match or exceed the fidelity of conventional ultra‑low‑temperature storage. It seeks to assess the technology’s ability to maintain diagnostic accuracy, including detection of clinically actionable variants in tumor samples. Another goal is to compare sequencing‑related artifact rates between ensilicated and cryogenically stored DNA to quantify improvements in data quality. Ultimately, the project aims to establish ensilication as a cold‑chain‑independent solution that enables more accessible global genomic testing and biobanking.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-02T17:19:43.801878+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001699","title":"Patient sample CCFB13 RNA-seq for Case Report","description":"A personalized cancer medicine approach would address therapy resistance, cancer metastasis, and limited options after standard of care is exhausted in advanced cancer participants. This approach may reduce the barriers to approved therapeutic assignment currently limited to a particular cancer type or patient demographic.\r\n\r\nRNA-seq data for Case Report manuscript in preparation","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001700","title":"Efficacy of dual KRAS G12D–EGFR blockade versus triple combinations in patient-derived models of KRAS G12D-mutant colorectal cancer","description":"RNA sequencing was performed on patient-derived xenograft (PDX)-derived organoid models of metastatic colorectal cancer (mCRC). The aim of this study was to characterize the transcriptional landscape of KRAS-mutant mCRC cells in response to therapeutic strategies targeting the EGFR and KRAS signaling pathways. Transcriptomic profiling was conducted following drug treatments to investigate molecular changes associated with single and combination therapies. A total of 24 samples were analyzed.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-30T14:26:52.820222+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001701","title":"Distinct tumor-immune landscapes drive rapid clinical responses to neoadjuvant checkpoint blockade","description":"\"Immune checkpoint blockade (ICB) induces rapid tumor regression in some patients, yet the underlying immunological events remain unclear. We performed single-cell RNA- and TCR-sequencing on paired longitudinal tumor biopsies of 19 patients with cutaneous squamous cell carcinoma to track immune dynamics during neoadjuvant anti-PD-1±anti-CTLA-4 therapy. Patients with (near-)complete pathological responses showed\r\nintratumoral CD8+ T cell activation and clonal expansion starting within one week after ICB initiation. Responding tumors exhibited distinct T cell landscapes skewed towards early- or late-dysfunction that underwent distinct on-treatment remodeling. Patient-derived tumor fragment cultures revealed that rapid responses were mediated, at least in part, via local immune reinvigoration. The distinct baseline T cell landscapes associated\r\nwith tumor microenvironments enriched for B cells or macrophages, which converged towards a shared phenotype upon antigen clearance. Collectively, these findings delineate the early T cell dynamics driving clinical response to neoadjuvant ICB and identify distinct tumor-immune landscapes mediating rapid tumor regression. Aim of the study: to understand the distinct immune dynamics upon ICB driving tumor clearance\"\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001702","title":"Personalized ctDNA detection and genomic profiling in the NeoRHEA Study","description":"In the management of early hormone receptor (HR)+, HER2-negative breast cancer, circulating tumor DNA (ctDNA) detection is an evolving yet promising diagnostic approach. We evaluated ctDNA detection using the personalized RaDaR assay in plasma samples from patients enrolled in the NeoRHEA clinical trial (NCT03065621), a single-arm, phase II study of neoadjuvant palbociclib and endocrine therapy administered over 4 months (four 28‑day cycles). Plasma samples were collected pre-treatment, after the first treatment cycle, prior to surgery, and one month post-surgery. At baseline, ctDNA positivity was detected in 55% of patients; however, this dropped to 5% during treatment and ctDNA became undetectable in all patients by one month post-surgery. CtDNA detection at baseline was higher in histological grade 3 tumors, lower in multifocal/multicentric tumors and higher in residual cancer burden (RCB) 3 tumors. Genomic analysis revealed MYC gene gains or amplifications were more frequent in ultrasound (US) responders, while PIK3CA gains were more common in US non-responders. Additionally, FAT1 losses were more frequently observed in patients with RCB 3. Our findings suggest that baseline ctDNA presence predicts poor response to neoadjuvant palbociclib and endocrine therapy, underscoring its potential as a biomarker to guide tailored therapeutic approaches in HR+/HER2-negative breast cancer.\r\n","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-09T17:09:50.174675+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001703","title":"snRNA-seq schizophrenia control Prefrontal cortex","description":"In this study, we performed RNA sequencing of single nuclei from the prefrontal cortex of donors with and without schizophrenia using the 10x Genomics Chromium Single Cell protocol. The project rationale is to determine cell type specific transcriptomic changes between the two groups and linking them to the risk for schizophrenia.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[40162239],"external_links":null,"is_released":true,"released_date":"2026-04-17T14:15:37.706007+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001704","title":"Multi-omics datasets (WES, RNA-seq) of mesothelioma MIST3 study, a phase IIA AXL/PD1 inhibition clinical trial","description":"This study comprises 26 mesothelioma patients with whole exome and RNA sequencing, aimed to reveal tumour intrinsic and extrinsic features that confer responsiveness. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001705","title":"LUAD RNAseq – LORD","description":"RNA-seq data from paired normal and adenocarcinoma lung samples obtained from 515 patients that underwent lung cancer surgery.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-10T10:40:09.349175+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001706","title":"Jeju Genome Project","description":"The Jeju Genome Project (JGP) is a multi-omics resource for precision medicine in a geographically distinct South Korean population. It comprises 5,309 participants (3,001 community-based; 2,308 hospital-based) with data spanning Whole-Genome Sequencing (WGS) and genotyping arrays. The hospital cohort is specifically enriched for neurological and rheumatic diseases and malignancies. By providing a population-specific reference panel, JGP enables high-resolution genetic architecture analysis, risk stratification, and the discovery of rare variants relevant to Jeju and broader East Asian populations.\r\n","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-25T14:03:25.669677+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001707","title":"Granzyme B-expressing regulatory B cells share the same origin as conventional blood B cells","description":"This study investigates the origin and characteristics of granzyme B-expressing regulatory B cells (GZMB⁺ Bregs), a subset implicated in immune regulation and graft tolerance following kidney transplantation. We analyzed the B cell receptor (BCR) repertoire of sorted GZMB⁺ and GZMB⁻ B cells from two healthy donors (Healthy Volunteers, HVs) and two drug-free tolerant kidney transplant recipients (TOLs).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-13T11:27:19.458179+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001708","title":"Whole exome sequencing of Zimbabwean patients with suspected Mendelian disorders","description":"This study presents whole exome sequencing data from Zimbabwean individuals with suspected Mendelian disorders, including sickle cell disease, Fanconi anemia, haemophilia, and muscular dystrophy. The dataset includes both affected individuals and family members to support inheritance-based analyses. Variant calling was performed using the Illumina DRAGEN pipeline, with downstream variant prioritisation and interpretation conducted using the Zi-Mendelian bioinformatics pipeline. This study supports rare disease genomics and precision medicine efforts in African populations.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-03-25T14:08:26.551455+01:00","is_deprecated":false},
{"accession_id":"EGAS50000001709","title":"scWGS of tumors resected from GBM patients at diagnosis and relapse (batch3, n=7 samples)","description":"Single cell whole genome sequencing (scWGS) were used to define the clonal architecture and evolutionary trajectories of glioblastoma. By resolving genomic copy number profiles at single-cell resolution, the study aims to identify the molecular programs that sustain tumor initiation and progression, and to map how treatment reshapes the cellular ecosystem. This work provides critical insight into intratumoral heterogeneity, reveals vulnerabilities within resistant subpopulations, and supports the development of more targeted therapeutic strategies for this highly lethal cancer. (batch3, n=7 samples)","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001710","title":"Variations in Cultured Invariant NKT Cells Using IL-2 or IL-15","description":"This dataset contains single-cell RNA sequencing (scRNA-seq) and cell surface protein data from human invariant Natural Killer T (iNKT) cells expanded ex vivo under two cytokine conditions: IL-2 and IL-15. iNKT cells were isolated from peripheral blood mononuclear cells of four healthy donors using anti-iNKT microbeads and cultured for four weeks with α-galactosylceramide-loaded CD1d-expressing feeder cells. After culture, live cells were selected using dead cell removal and processed on the 10x Chromium platform (Next GEM Single Cell 3' v3.1) to generate paired gene expression and feature barcode libraries. Samples were pooled in pairs for processing; a TCR hashtag antibody (present or absent) was used to assign individual sample identity within each pool. Feature barcoding was additionally used to quantify seven cell surface proteins: CD122 (IL-2Rβ), CD62L (L-selectin), CD314 (NKG2D), CD223 (LAG-3), CD279 (PD-1), CD150 (SLAM), and CD319 (CRACC). Libraries were sequenced on the Illumina NovaSeq 6000. The dataset contains raw FASTQ files.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001711","title":"Reduced platelet formation associated with serine metabolic dysregulation in integrin αIIbβ3-deficient megakaryocytes ","description":"Glanzmann Thrombasthenia (GT) is characterized by absent platelet aggregation in response to all agonists except ristocetin and is caused by recessive inactivating variants in ITGA2B or ITGB3. While GT patients typically are described as having normal platelet counts, autosomal dominant activating variants in ITGA2B or ITGB3 cause macrothrombocytopenia. Interestingly, in our cohort of 16 GT patients, eight consistently exhibited platelet counts at the lower end of the normal range. We studied the role of integrin αIIbβ3 in platelet formation using megakaryocytes (MKs) derived from genetically modified immortalized megakaryocyte cell lines (imMKCLs), focusing on two modifications of ITGB3: ITGB3-/- (inactivating) and ITGB3WT/D673_E713del (activating). In static differentiation cultures, ITGB3-/- and ITGB3WT/D673_E713del imMKCLs exhibited normal MK differentiation but reduced proplatelet formation. Platelet production was also impaired in a 3D silk-based bone marrow system and in shaking cultures, confirming a quantitative role for ITGB3 in platelet production, independent of the type of variant. While TRAP-activated in vitro-generated platelets lacking αIIbβ3 failed to bind the activation-dependent PAC-1 antibody, ITGB3WT/D673_E713del platelets bound PAC-1 prior to activation mimicking the patient’s phenotype. Transcriptome profiling and metabolomic analyses ofintegrin αIIbβ3 deficient MKs revealed impaired serine metabolism and downregulation of SLC3A2 (CD98hc), an amino acid transporter chaperon known to interact with the β3 subunit. Flow cytometry confirmed decreased CD98hc in mutant MKs, while re-expression of wild-type ITGB3 in ITGB3-/- MKs restored αIIbβ3 and CD98hc expression, normalized proplatelet formation, and enhanced serine uptake. These results uncover a previously unrecognized role of integrin αIIbβ3 in coupling serine metabolism to platelet biogenesis.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-07T15:34:29.579331+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001712","title":"Liquid-based genomic profiling in high-risk localized prostate cancer.","description":"In this study, we evaluated the feasibility and performance of tissue and liquid-based genomic profiling in patients with high-risk localized prostate cancer. Genomic DNA from 12 FFPE tissue samples and cell-free DNA from 27 plasma samples were analyzed using Illumina TruSight Oncology (TSO) 500 panels.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-07T17:44:10.077977+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001713","title":"Doubleedged phenotype of compensated dyserythropoiesis and monocytic arrest in TP53-mutant clonal haematopoiesis.","description":"TP53-mutant clonal haematopoiesis (CH) confers high-risk for myeloid malignancies, but selective forces\r\ndriving clonal expansion are unclear. We analysed 721 older individuals (mean age 69 years), where TP53-\r\nmutant CH was independently associated with increased red cell mean corpuscular volume. Single-cell\r\ntranscriptomics of bone marrow (BM) mononuclear cells revealed disrupted metabolic coordination in\r\nerythroid precursors, with heightened oxidative phosphorylation but impaired coupling to cell cycle and\r\nantioxidant responses. Under cytokine-induced stress, TP53-mutant progenitors demonstrated increased\r\nclonogenicity and metabolic adaptability, partially rescuing erythroid differentiation while imposing monocytic\r\ndifferentiation arrest. Functional assays confirmed that heterozygous TP53 mutations confer survival\r\nadvantage under metabolic inhibition, linked to preserved mitochondrial reserve. Exploratory clinical and\r\nproteomic analyses suggest hepatic and renal dysfunction as potential stressors selecting for TP53-mutant\r\nclones. These findings indicate that metabolic stress promotes TP53-mutant clonal fitness, creating a double-\r\nedged phenotype of compensatory erythropoiesis and pre-leukaemic myeloid dysplasia, highlighting\r\nmetabolic pathways as targets for prevention of progression to MDS/AML.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001714","title":"Recurrent/Metastatic Adenoid Cystic Carcinoma Treated with Axitinib and Avelumab","description":"Data from patients with adenoid cystic carcinoma treated with combination of VEGFR inhibitor axitinib and anti-PD-L1 avelumab. Eligible patients had R/M ACC with progression within 6 months before enrollment. The primary end point was objective response rate (ORR) per RECIST 1.1; secondary end points included progression-free survival (PFS), overall survival (OS), and toxicity. The study reached its primary end point with ≥4 PRs in 28 evaluable patients (confirmed ORR of 18%).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-08T14:41:32.08574+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001715","title":"Prospective Lynch Syndrome Database materials","description":"The Prospective Lynch Syndrome Database data. These data contain necessary clinical tables to reproduce the previous PLSD papers using the clinical tables for individual level cancer incidence by age, sex and MMR gene affected. The tables contain the demographics, individual cancers at given age, and therapeutic and prophylactic surgeries removing total or partial organs.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[40231433,37181409],"external_links":null,"is_released":true,"released_date":"2026-04-09T08:25:28.800267+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001716","title":"Metagenomic analysis of vaginal and breast milk microbiomes to study maternal-to-infant microbial transmission and early-life microbiome development.","description":"Metagenomic Characterization of Vaginal and Breast Milk Microbiomes in Lifelines NEXT to Investigate Maternal-to-Infant Microbial Transmission.\r\n","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-11T09:10:43.491012+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001717","title":"Human intraepithelial lymphocytes in control and compensated cirrhosis samples","description":"single cell (GEM x5' v3) sequencing data AND TCRsequencing data of 2 healthy controls and 2 compensated cirrhosis patients","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001718","title":"Transcriptomic and epigenetic characterization of ex vivo expanded T cells","description":"In this study, we investigated the transcriptomic and epigenetic landscape of primary human T cells stimulated ex vivo under various conditions. Naïve CD8+ T cells isolated from healthy donor PBMCs were subjected to ex vivo stimulation and used for bulk RNA-seq and ATAC-seq library preparation. These datasets were generated to characterize global changes in gene expression and chromatin accessibility associated with ex vivo T-cell stimulation. The data may support comparative analyses of molecular states arising under distinct culture conditions.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-28T09:57:17.922512+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001719","title":"Motif-directed chromatin repression by BCL11B shapes ectopic targeting and lineage commitment","description":"BCL11B encodes a critical T-lineage transcription factor that is implicated as both an oncogene and a tumor suppressor in acute leukemia. Despite its central role in development and malignancy, a basic understanding of the sequence determinants of BCL11B activity remains obscure. Here, we define two functionally distinct modes of BCL11B engagement with chromatin: Most detectable BCL11B binding events are determined by pre-existing patterns of chromatin accessibility and RUNX1 occupancy. In contrast, BCL11B directs chromatin closing at genomic regions enriched for DNA motifs containing the core “TGACC” sequence, which are most prevalent in non-T lineages. These BCL11B-closed target sites cannot be identified from conventional BCL11B chromatin profiling approaches yet represent the primary mechanism by which BCL11B regulates gene expression. We provide evidence that cell of origin impacts the ability of BCL11B to repress lineage-inappropriate gene programs, thereby promoting lineage skewing. Together, these findings define a motif-centered determinant of BCL11B repression and explain how BCL11B controls lineage specification.  ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-14T09:29:38.701917+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001720","title":"Morphological and gene expression changes in SCA1 cerebral organoids suggest neurodevelopmental disease characteristics","description":"Cerebral organoids were generated from controls, individuals with SCA1 and gene-edited SCA1 hiPS cells. At day 31 and day 60, RNA sequencing was performed showing differential of several genes involved in neural development.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-17T14:14:31.845894+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001721","title":"Whole-Exome Sequencing in Mexican Patients with Testicular Germ Cell Tumors","description":"In this study, we performed whole-exome sequencing in 40 clinically well-characterized Mexican patients with testicular germ cell tumors. Paired tumor and peripheral blood samples were analyzed to characterize the genomic landscape, including both single nucleotide variants (SNVs) and copy number variations (CNVs).","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[35565196],"external_links":null,"is_released":true,"released_date":"2026-04-23T09:38:34.75145+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001722","title":"Tumor-resident T cells and dendritic cells form an in situ archetype during immunotherapy response in melanoma.","description":"Tumor-resident (TR) T cells, known as tissue-resident memory (TRM) T cells in mice, play a central role in melanoma immunosurveillance, yet their contribution to immune checkpoint inhibitors (ICI) therapy has not been comprehensively explored. We performed spatial and single-cell profiling on 32 metastatic melanoma lymph node samples, from treatment-naïve, ICI-resistant, or ICI-responsive patients. Here we show that tumor areas in ICI-responders were enriched in both CD8+ and CD4+ TR. CD8+ TR were hyperexpanded, and both CD8+ and CD4+ TR cells upregulated cytotoxicity-related gene expression, suggesting functional anti-tumor immunity. Conversely, ICI-resistant tumors displayed chronic IFN-γ response pathways, linked to T cell exhaustion. We further identified a spatially organized immune triad composed of CD8⁺ TR, CD4⁺ TR, and type-3 dendritic cells (DC3) that is exclusive to responding tumors. These findings define coordinated cellular interactions within the tumor microenvironment that underpin successful immunotherapy and provide a framework for spatial biomarkers of response. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-23T16:46:00.240138+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001723","title":"Low intratumoral macrophage infiltration is a consistent immune microenvironment predictor of poor outcome in lymphoma patients treated with R-CHOP but not Pola-R-CHP ","description":"The lymphoma microenvironment is a key contributor to treatment efficacy and a focus of active investigation. Yet, the adaptive interplay between immune infiltrates, malignant cells and treatment outcomes remains incompletely understood. Currently, little is known about how lymphoma cellular and functional heterogeneity may influence outcomes in patients treated with antibody drug conjugates (ADC), designed for lymphoma-targeted delivery of cytotoxic agents. Here, we evaluated the association of lymphoma immune microenvironment with treatment outcomes using tissue biopsies from 1,279 diffuse large B-cell lymphoma (DLBCL) patients treated with anti-CD20+chemo or Pola-R-CHP as front line therapies.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-28T14:08:18.902288+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001724","title":"A study to investigate the IgE recall in human allergy","description":"IGHV sequences of the IgE and IgG repertoire from the blood and nose of 14 birch pollen allergic subjects provoked intranasally with birch pollen extract and followed for up to 10 weeks after provocation","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001725","title":"Feasibility of cell-free RNA Profiling in Diffuse Large B-Cell Lymphoma","description":"Transcriptomic profiling of plasma-derived cell-free RNA in diffuse large B-cell lymphoma patients before and after treatment using next-generation sequencing, demonstrating technical feasibility of cfRNA isolation from 1 mL plasma, characterizing batch effects and RNA fragment composition, and identifying candidate genes for biomarker discovery and disease monitoring.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001726","title":"Expanding CIRdb, a comprehensive catalog of whole-exome sequencing data of Canary Islanders","description":"This study aimed to comprehensively characterize the full spectrum of small genetic variation among 920 unrelated donors from this population based on whole-exome sequencing data to further develop CIRdb as the Canary Islanders-specific reference catalog of genetic variation.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-10T11:06:07.832312+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001727","title":"Cellular Analysis of Resistance and Evolution (CARE) IDH-mutant glioma dataset","description":"In IDH-mutant glioma, genetic evolution and cellular heterogeneity across and within tumors may drive therapeutic resistance. Here, we analyzed 35 longitudinal patients by single-nucleus RNA-sequencing with a subset also characterized by bulk tumor DNA sequencing to better understand IDH-mutant glioma evolution.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-05T08:53:31.191346+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001728","title":"FutureMS RNA sequencing of sorted peripheral immune cell subsets in early multiple sclerosis","description":"This dataset comprises bulk RNA sequencing data generated from fluorescence-activated cell sorting (FACS)–purified peripheral immune cell subsets from participants in the FutureMS study, a prospective population-based inception cohort of individuals with newly diagnosed relapsing–remitting multiple sclerosis (RRMS) in Scotland.\r\n\r\nRNA sequencing was performed on sorted CD4+ T cells, CD8+ T cells, CD14+ monocytes, and CD19+ B cells obtained from peripheral blood samples collected prior to initiation of disease-modifying therapy.\r\n\r\nThe dataset is linked to comprehensive clinical and radiological phenotyping, including longitudinal clinical outcomes, MRI measures of disease activity, and circulating biomarkers.\r\n\r\nThese data enable investigation of immune cell–specific transcriptional profiles, host–pathogen interactions, and molecular determinants of early disease activity and progression in multiple sclerosis.\r\n\r\nAll data have been pseudonymised prior to deposition and are available via controlled-access mechanisms in accordance with participant consent and governance approvals.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001729","title":"scWGS of tumors resected from GBM patients at diagnosis and relapse (batch4, n=1 sample)","description":"Single cell whole genome sequencing (scWGS) were used to define the clonal architecture and evolutionary trajectories of glioblastoma. By resolving genomic copy number profiles at single-cell resolution, the study aims to identify the molecular programs that sustain tumor initiation and progression, and to map how treatment reshapes the cellular ecosystem. This work provides critical insight into intratumoral heterogeneity, reveals vulnerabilities within resistant subpopulations, and supports the development of more targeted therapeutic strategies for this highly lethal cancer. (batch4, n=1 sample)","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001730","title":"High grade serous ovarian cancer germline exome sequencing","description":"This cohort includes matched germline samples from the same patient cohort. Germline DNA was isolated from whole blood and normal tissue for whole exome sequencing.\r\n\r\n","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-02T14:59:58.902153+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001731","title":"High grade serous ovarian cancer tumor exome sequencing","description":"Whole exome sequencing data generated from 25 human high grade serous ovarian cancer (HGSOC) specimens. These data were used to characterize somatic mutations, copy number alterations, and genomic features. Raw sequencing data are provided as BAM files.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-02T14:59:58.902153+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001732","title":"Single-cell multi-omics profiling of immune reconstitution following peripheral blood stem cell transplantation","description":"This study investigates immune reconstitution in the bone marrow following allogeneic hematopoietic stem cell transplantation. Single-cell RNA sequencing, including gene expression, antibody-derived tag, and T cell receptor and B cell receptor repertoire profiling, was performed on peripheral blood stem cell donor grafts and recipient bone marrow samples collected before and after transplantation. The study focuses on comparing PTCy-haplo and conventional HLA-matched transplantation to understand differences in post-transplant immune dynamics.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001733","title":"RNA-seq of MPNSTs","description":"Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are highly aggressive soft-tissue sarcomas with a poor prognosis and a lack of therapeutic options. In this study, we analyse the whole-transcriptome MPNST and combine them with WGS data from a partially overlapping sample set. These analyses and the inclusion of another public dataset allow us to identify three genomic MPNST subgroups with distinct biological and clinicopathological features that can inform management and precision treatments.  Published in \"Identification of Malignant Peripheral Nerve Sheath Tumor (MPNST) subtypes with distinct genomic identities.\" ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-23T13:04:57.20886+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001734","title":"WGS of MPNSTs and ANNUBPs","description":"Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are highly aggressive soft-tissue sarcomas with a poor prognosis and a lack of therapeutic options. In this study, we analyse the whole genomes of 20 MPNSTs and 7 ANNUBPs to find recurrent genomic alterations that can help us better understand the biology of MPNSTs. Merging this data with another public dataset, we are able to identify three genomic MPNST subgroups with distinct biological and clinicopathological features that can inform management and precision treatments.  Published in \"Identification of Malignant Peripheral Nerve Sheath Tumor (MPNST) subtypes with distinct genomic identities.\"","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-23T13:04:53.587851+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001735","title":"Spatial Transcriptomic data from Invasive lobular breast carcinoma (ILC)","description":"Spatial transcriptomic data from Invasive lobular breast carcinoma (ILC)\r\nDjerroudi et al, Nature Communication","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-10T14:30:20.473511+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001736","title":"Nanopore Sequencing in adults with autism spectrum disorder (ASD) without intellectual disability","description":"This pilot study investigates the genetic and epigenetic underpinnings of late-diagnosed autism spectrum disorder (ASD) without intellectual disability or language impairment using long-read nanopore whole-genome sequencing. This approach allows the simultaneous analysis of complex structural variants (SVs) and DNA methylation patterns in genomic regions often missed by short-read methods, such as intronic, non-coding and repetitive regions.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-04T10:59:42.554249+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001737","title":"NGS-based tracking of donor-reactive T cells in HLA-mismatched kidney transplantation following co-transplantation of donor bone marrow and recipient regulatory T cells for tolerance induction without irradiation","description":"Co-transplantation of donor bone marrow together with concomitant polyclonal autologous regulatory T cell infusion is a promising strategy to induce tolerance in HLA-mismatched kidney transplantation without irradiation. We tested this strategy in an academic phase I/IIa controlled trial. The study group received polyclonal autologous regulatory T cells and donor bone marrow cells following HLA-mismatched kidney transplantation. Next generation sequencing based high throughput T cell receptor sequencing was performed on pre- and post-transplant peripheral blood samples from multiple timepoints to profile the T cell receptor repertoire, including donor-reactive clonotypes identified via mixed lymphocyte reactions. T cell receptor sequencing enabled longitudinal tracking of T cell clonotypes and repertoire dynamics across study timepoints.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001738","title":"ImmunoSep Single-Cell Transcriptomics","description":"subset of the ImmnoSep Clinical Trial Cohort for single-cell transcriptomics using BD Rhapsody. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001739","title":"Transcriptomic landscape for African-specific low-grade prostate cancer","description":"Prostate cancer is characterised by significant ancestral disparities, with men of African ancestry experiencing higher mortality rates. This study aims to characterise the transcriptomic divergence between African and European ancestral low-grade tumours (n = 116) to identify molecular features contributing to clinical outcomes. Using total RNA sequencing on fresh-frozen tissue, the project investigates differential gene expression, pathway enrichment, and cell-type composition across diverse cohorts.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001740","title":"PDHGG DNA sequencing from tumours and PDX","description":"Whole exome and targeted DNA sequencing from paediatric diffuse high grade gliomas and patient derived orthotropic xenografts. 79 samples were profiled from 35 patients. Data is provided as BAM files aligned to GRCh37","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001741","title":"Exploring the evolution of atypical fibroxanthoma to pleomorphic dermal sarcoma: a genomic and pharmacological insight","description":"The study includes an integrated genomic and pharmacological analysis of atypical fibroxanthoma (AFX) and its progression to pleomorphic dermal sarcoma (PDS), two rare cutaneous mesenchymal tumors with overlapping clinical and histological features but distinct prognostic profiles. The findings will shed light on the molecular mechanisms underlying this progression and provide preliminary evidence for potential therapeutic vulnerabilities, particularly in the context of targeted and immune-based approaches.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-24T13:57:23.601896+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001742","title":"Whole transcriptome sequencing of the dMMR colorectal cancer cohort","description":"We leveraged the ImmunoID NeXT platform, an Immune-enhanced multiomics platform to profile a cohort of patients with dMMR CRC. This sub-study includes the whole transriptome sequencing data","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-15T09:32:37.052631+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001743","title":"TCR and BCR sequencing of the dMMR colorectal cancer cohort","description":"We leveraged the ImmunoID NeXT platform, an Immune-enhanced multiomics platform to profile a cohort of patients with dMMR CRC. This sub-study includes the TCR and BCR sequencing data\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-15T09:32:37.052631+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001744","title":"Whole exome sequencing of the dMMR colorectal cancer cohort","description":"We leveraged the ImmunoID NeXT platform, an Immune-enhanced multiomics platform to profile a cohort of patients with dMMR CRC. This sub-study includes the whole exome sequencing data","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-15T09:32:37.052631+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001745","title":"Single-cell RNA-seq of Human Bone Marrow Mesenchymal Stromal Cells Driving Bone Marrow Organoid Formation","description":"Raw single-cell transcriptomic data capturing the intrinsic programs of human bone marrow mesenchymal stromal cells (hBM-MSCs) during in vivo formation of bone marrow organoids in synthetic PEG hydrogels, without external stimuli.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001746","title":"Predictive value of genomic, transcriptomic and epigenetic biomarkers in patients with recurrent and/or metastatic HNSC treated with PD-1/PD-L1 inhibitors","description":"Immune checkpoint inhibitors have improved survival in several solid tumors, including head and neck squamous cell carcinoma (HNSCC). However, current use of PD-1/PD-L1 inhibitors relies on PD-L1 expression, which does not reliably predict patient response. Therefore, better predictive biomarkers are needed to identify which patients benefit from immunotherapy. Previous studies suggest that genomic and transcriptomic features may help predict treatment response. This study aims to integrate genomic, transcriptomic, and methylomic data from 31 patients with recurrent/metastatic HNSCC to identify new biomarkers of resistance to anti-PD-1/PD-L1 therapy.\r\n\r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-20T09:59:58.852563+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001747","title":"Analysis of MPNST progression at single-cell resolution","description":"Malignant Peripheral Nerve Sheath Tumors (MPNST) are soft-tissue sarcomas with poor prognosis and a lack of treatment options. About half of them arise in people with Neurofibromatosis Type 1 (NF1). In this study, we set out to explore the malignant progression and tumor heterogeneity by  exploring the different tumors along the MPNST progression at the single cell level. This work is part of the project \"NF1-Associated Peripheral Nerve Sheath Tumors at Single-Cell Resolution: Heterogeneity, Tumor Growth, and Malignant Progression\".","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-30T15:28:07.366065+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001748","title":"Bulk transcriptomic profiling of human skeletal progenitor cells during early in vivo differentiation","description":"Bulk RNA sequencing (BRB-seq) was performed on human bone marrow stromal cells (hBMSCs) isolated before and after in vivo implantation to capture early transcriptional changes associated with osteogenic commitment. Libraries were generated using a barcoded 3′ mRNA sequencing approach with poly(A) selection and unique sample barcodes, enabling multiplexed transcriptome profiling. Sequencing was carried out on an Illumina platform, producing short-read data suitable for differential gene expression and pathway analysis. The dataset provides insight into extracellular matrix remodeling programs and endochondral ossification signatures underlying donor-specific regenerative potential.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001749","title":"scWGS of tumors resected from GBM patients at diagnosis and relapse (batch5, n=1 sample)","description":"Single cell whole genome sequencing (scWGS) were used to define the clonal architecture and evolutionary trajectories of glioblastoma. By resolving genomic copy number profiles at single-cell resolution, the study aims to identify the molecular programs that sustain tumor initiation and progression, and to map how treatment reshapes the cellular ecosystem. This work provides critical insight into intratumoral heterogeneity, reveals vulnerabilities within resistant subpopulations, and supports the development of more targeted therapeutic strategies for this highly lethal cancer. (batch5, n=1 sample)","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001750","title":"snRNA: Comparison of the transcriptomic profile of CD34+ cells of transformed myelofibrosis patients vs non-transformed MF patients.","description":"11 samples of MPN patients were processed. 1 sample is a pooled patients of 2 donors. This study contains the snRNA data of multiome and are complemented by scATACseq data. Samples were taken at the time of the MPN diagnosis. Some samples are known to have developed AML after the MPN diagnosis.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001751","title":"scATAC: Comparison of the transcriptomic profile of CD34+ cells of transformed myelofibrosis patients vs non-transformed MF patients.","description":"11 samples of MPN patients were processed. 1 sample is a pooled patients of 2 donors. This study contains the snRNA data of multiome and are complemented by snRNAseq data. Samples were taken at the time of the MPN diagnosis. Some samples are known to have developed AML after the MPN diagnosis.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001752","title":"A prognostic human brain network for diffuse midline glioma","description":"Diffuse midline glioma (DMG) are near-universally lethal tumours of the paediatric central nervous system. In animal models, DMG form brain-wide, integrated networks through neuron-to-glioma synapses and glioma-to-glioma gap junctional coupling. This extensive connectivity robustly promotes the growth and invasion of DMG and other glial malignancies through paracrine mechanisms and direct neuron-to-glioma synapses. The organisation and clinical implications of these connections in the living human brain, however, remain to be elucidated. Here, we develop tumour network mapping to compute the brain-wide connectivity profile of DMG: defining a conserved brain network across pontine and thalamic DMG associated with patient short-term survival (DMG network). Tumour functional connectivity with the DMG network was independently predictive of patient overall survival across two external validation cohorts. Tumour growth mapped to DMG network-specific trajectories and peak, in-network neurometabolic changes across development spatiotemporally aligned with the peak age incidence of DMG. Single-nucleus RNA-sequencing confirmed diverse synaptic gene enrichment in high-connectivity DMG. Strikingly, incidental surgical resection of high-connectivity thalamic DMG tissue conferred a significant survival advantage. Collectively, these data define a conserved and prognostically important brain network in children with DMG, consistent with the hypothesis that DMG exploit otherwise healthy brain circuits to promote tumour growth.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-16T16:50:37.523533+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001753","title":"scWGS of tumors resected from GBM patients at diagnosis and relapse (batch6, n=1 sample)","description":"Single cell whole genome sequencing (scWGS) were used to define the clonal architecture and evolutionary trajectories of glioblastoma. By resolving genomic copy number profiles at single-cell resolution, the study aims to identify the molecular programs that sustain tumor initiation and progression, and to map how treatment reshapes the cellular ecosystem. This work provides critical insight into intratumoral heterogeneity, reveals vulnerabilities within resistant subpopulations, and supports the development of more targeted therapeutic strategies for this highly lethal cancer. (batch6, n=1 sample)","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001754","title":"Single-cell RNA sequencing of mouse splenic B1a cells","description":"B1a cells are a population of B cells in spleen which are involved in regulation of inflammation. Upon butyrate treatmetn and rIl27 treatment, B1a cells differentiate into B10 cells which exhibit role of regulatory B cells to mitigate inflammation and reduce disease burden of inflammatory diseases. we performed single-cell RNA sequencing of mouse splenic B1a cells across three conditions - control, butyrate treatment and rIL27 treatment for understanding B10 cell transcriptome across three conditions.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001755","title":"Single Cell Analysis of the Tumor Microenvironment Landscape Across the Disease Spectrum of Multiple Myeloma","description":"Multiple myeloma is a plasma cell malignancy that progresses through distinct clinical stages from the precursors monoclonal gammopathy of undetermined significance and smoldering myeloma to newly diagnosed symptomatic and relapsed/refractory disease. Understanding tumor microenvironment (TME) evolution along this continuum is critical for uncovering immune dysregulation mechanisms and therapeutic resistance pathways. We thus performed single-cell RNA, T-cell receptor, and B-cell receptor sequencing on bone marrow aspirate samples from 235 patients spanning the disease spectrum. This comprehensive dataset revealed dynamic changes in the abundance and functional states of diverse immune populations, including T-, natural killer, B-, and myeloid cells. Using non-negative matrix factorization, we defined five distinct TME subtypes, or “immune ecotypes” based on the coordinated co-occurrence of specific cell populations. Each ecotype was characterized by unique cellular compositions, cell–cell communication networks, signaling response patterns, transcription factor activity, and recurrent gene modules. Importantly, these ecotypes transcend traditional clinical classifications and reflect convergent immune adaptations to evolving microenvironmental pressures. Our study presents a comprehensive single-cell immune atlas of multiple myeloma and its precursors, offering new insights into TME organization and progression. These findings underscore the importance of TME context in shaping immune function and may guide development of stage-specific or ecotype-targeted immunotherapies.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001756","title":"SCI-MAP: Single Cell Microgel embedded iPS-cells to map molecular variability of cell differentiation using a systems biology approach","description":"In the SCI-MAP project we will map cell states encountered across a previously established 49 day in vitro chondrogenic differentiation protocol. We do this to optimise the differentiation process for therapeutic and in vitro modelling ends. We collect epigenetic open chromatin and phenotypic transcriptome data to determine cell states and so performed single nucleus sequencing in two modalities: RNA- and ATAC-sequencing. Data was collected in a time series experiment at 7 points: Days 0, 3, 6, 8, 14, 21, and 49, starting with the first pilot data from day 21 (D21) then the actual experiment time series 1 (TS1) of days 0, 3, 6, 8, 14, and 49.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-20T16:27:41.191796+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001757","title":"RAS Pathway Mutations Orchestrate Chromatin Reconfiguration and Transcriptional Rewiring in Colorectal Cancer","description":"Mutations in the RAS signaling pathway are present in approximately 40% of colorectal cancers (CRCs). Tumors harboring KRAS or BRAF mutations display distinct molecular characteristics, including differences in their mutational profiles, gene expression patterns, and epigenetic modifications. To investigate the molecular mechanisms regulated by RAS pathway mutations, we conducted ATAC-seq analysis using isogenic cell line models derived from HCT116 and RKO cell line.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001758","title":"Archaean stimulation of human primary PBMCs and PBMCs monocytes","description":"Prevalent in the human gut yet lacking canonical cell wall-derived host-recognition motifs found in bacteria, human-associated archaea Methanosphaera stadtmanae and Methanobrevibacter smithii show immune activity and disease links but remain largely underexplored. Time-resolved RNA-seq in human PBMCs identified an immune program shared with bacterial or viral stimuli across both archaeal species, yet their kinetics diverge, with M. stadtmanae inducing earlier and stronger activation and M. smithii eliciting more gradual responses. Among conserved early-upregulated genes, two classes emerged: Class I is preferentially induced by M. stadtmanae, whereas Class II is similarly induced by both species. To investigate the origin of the Class I/II phenotype, we measured phagocytosis and applied TLR8 inhibition, finding greater early phagocytosis with M. stadtmanae and broad TLR8 dependence across readouts. Mechanistically, ChIP-qPCR demonstrated that M. stadtmanae, but not M. smithii, drives NF-κB p65 binding at Class I promoters, while STAT1/2 binding at Class II promoters occurs with both stimuli. Dose-response analyses with RNA inputs established distinct activation thresholds, with Class II at low dose (via STAT1/2) and Class I only at higher dose (via p65). Together, these findings define an input-tuned logic in which archaeal inputs gate TLR8-governed immune programs. More broadly, variation in archaeal inputs may tune immune tone and help explain disease links, supporting dose-aware TLR8 agonist/antagonist modulation for diagnosis, therapy, and adjuvant design.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-17T17:09:32.230319+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001759","title":"Whole-genome sequencing and H3K4me3 profiling of plasma cell-free DNA","description":"Epigenomic characterization of breast cancers by profiling circulating nucleosomes isolated from patient plasma using cell-free chromatin immunoprecipitation followed by sequencing (cfChIP-seq).\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-01T13:21:44.583475+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001760","title":"E-cadherin inactivation shapes tumor microenvironment specificities  in invasive lobular carcinoma","description":"Invasive lobular breast carcinoma (ILC) shows specific stromal features, T lymphocyte infiltration (TIL) being associated with poor prognosis. Here, we reveal the involved mechanism by performing single cell RNA sequencing, combined immunohistochemistry, deconvolution of bulk RNA sequencing from large retrospective ILC series, and functional assays using primary cells. We show that ILC accumulates FAP+ inflammatory cancer-associated fibroblasts (iCAF) through a previously undescribed mechanism mediated by E-cadherin/CDH1 on CAF plasticity. Indeed, CDH1 inactivation in ILC cancer cells prevents differentiation of iCAF into myofibroblastic CAF (myCAF), leading to iCAF accumulation. In turn, iCAF attract TILs into the tumor center and shape their spatial organization in ILC. Subsequently, CDH1-inactivated ILC cancer cells promote immune escape by lack of retention and activation of ITGAE-expressing resident memory CD8+ T lymphocytes (TRM). Hence, our study uncovers reciprocal interactions between CDH1-inactivated cancer cells, iCAF and CD8+ TRM, gaining insight into the underlying mechanism associated with the distinctive stromal reaction observed in ILC and revealing why and how TILs have a poor prognosis in ILC patients, a mechanism that can be generalized to other CDH1-inactivated cancer types. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-24T16:18:09.844384+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001761","title":"μSeq: Universal mutation rate quantification via deep sequencing of a single clonal expansion","description":"We use patient-derived colorectal cancer organoids to introduce µSeq, a universal framework for inferring mutation rates in diverse biological systems. Our approach extracts mutation rates from deep sequencing of single clonal expansions, with a time gain of tenfold or more compared to a mutation-accumulation line, at the cost of three billion read whole-genome sequencing.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-30T16:20:59.760024+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001762","title":"Wolff et al, 2026, Prime editing of human hematopoietic stem cells for correction of GATA2 deficiency","description":"HTAS data relating to manuscript Wolff et al, 2026, Prime editing of human hematopoietic stem cells for correction of GATA2 deficiency","abstract":null,"study_type":"Synthetic Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-17T17:33:56.515688+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001763","title":"Oral microbiome metagenomic sequencing - Human Phenotype Project (HPP)","description":"This study characterizes the oral microbiome of participants enrolled in the Weizmann Institute Human Phenotype Project (HPP), a longitudinal cohort study. Oral swab samples were collected and subjected to shallow whole-genome sequencing using the Gencove low-pass sequencing platform. Raw reads include residual human host sequences in addition to microbial sequences. The dataset comprises metagenomic FASTQ files from [N] participants. Data access is restricted in accordance with participant informed consent and Weizmann IRB approval","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-20T10:02:24.007631+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001764","title":"ATAC-seq of iPSC-derived NF1-CDKN2A-PRC2 deficient neural crest mimicking MPNST progression","description":"ATAC-seq data used in the paper \"iPSC-derived NF1-CDKN2A-PRC2 deficient neural crest mimics MPNST glial-to-neuro-mesenchymal transition and uncover new therapeutic opportunities\" by Uriarte-Arrazola, 2026. The uploaded data was used to explore and validate the cellular model as an MPNST progression model.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-30T15:28:10.41013+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001765","title":"WGS of iPSC-derived NF1-CDKN2A-PRC2 deficient neural crest mimicking MPNST progression","description":"WGS data used in the paper \"iPSC-derived NF1-CDKN2A-PRC2 deficient neural crest mimics MPNST glial-to-neuro-mesenchymal transition and uncover new therapeutic opportunities\" by Uriarte-Arrazola, 2026. The uploaded data was used to explore and validate the cellular model as an MPNST progression model.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-30T15:28:10.41013+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001766","title":"RNA-seq of iPSC-derived NF1-CDKN2A-PRC2 deficient neural crest mimicking MPNST progression","description":"RNA-seq data used in the paper \"iPSC-derived NF1-CDKN2A-PRC2 deficient neural crest mimics MPNST glial-to-neuro-mesenchymal transition and uncover new therapeutic opportunities\" by Uriarte-Arrazola, 2026. The uploaded data was used to explore and validate the cellular model as an MPNST progression model.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-04-30T15:28:10.41013+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001767","title":"Plasma sequencing data for ctDNA monitoring for NSCLC in TRACERx","description":"Ultrasensitive circulating tumour DNA (ctDNA) detection can stratify clinical risk in early-stage non-small cell lung cancer (NSCLC). Here, we applied a whole-genome, tumour-informed approach to study ctDNA in more than 400 NSCLC of the TRACERx project. This study captures the plasma sequencing data from the project.\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-05T10:18:59.353156+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001768","title":"HiC data of human LCLs ","description":"HiC data of human LCLs data in two cases with non-coding structural variants in the FOXG1 TAD. Both processed data and raw sequencing. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-11T17:15:16.825486+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001769","title":"Human colon stem cells actively suppress regenerative plasticity in the colonocyte lineage","description":"Insights into intestinal stem cell functioning during homeostasis and repair have been predominantly derived from genetic mouse models. This is in stark contrast to the largely unexplored situation in the human gut, where the underlying mechanisms and stimuli that induce regeneration are poorly understood. Here, we developed genetic strategies to characterize fluorescently labelled LGR5+ stem cells in normal human colon organoids. In parallel, we made diphtheria toxin-mediated cell type ablation compatible with human cells, thereby enabling in-depth interrogation of the sequence of events during depletion and reappearance of stem cells. Following LGR5+ stem cell depletion, most of the remaining epithelial cells entered a regenerative state characterized by fetal-like expression programs. Strikingly, this regenerative response was already initiated before stem cell loss, indicative of active communication between functional stem cells and progeny during homeostasis. We identified inactivation of retinoid X receptor (RXR) as a crucial trigger to initiate the regenerative response in colonocytes, with human colon stem cells being the producer of the RXR stimulus retinoic acid. Thus, stem cell-derived retinoic acid actively suppresses the regenerative state in colonocytes, explaining how surviving cells sense stem cell loss.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001770","title":"Single-cell RNA-seq of human mesenchymal stromal cells during stimulus-free in vivo bone marrow organoid formation","description":"This study investigates the intrinsic differentiation capacity of human bone marrow mesenchymal stromal cells (hBM-MSCs) during in vivo bone formation. Cells were encapsulated in synthetic TG-PEG hydrogels and implanted subcutaneously in immunocompromised mice in the absence of exogenous osteoinductive factors to assess their endogenous regenerative potential. Single-cell RNA sequencing was performed on human cells recovered from the implants to characterize transcriptional states associated with endochondral ossification. The dataset captures mesenchymal, chondrogenic, and osteogenic populations and provides insight into stromal cell-driven bone organoid formation in vivo.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001771","title":"PDTTCs platform to study GBM immunotherapies","description":"PDTTCs platform for assessign TCE treatment in glioblastoma patients","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001772","title":"Enhancing  maturation of human neuromuscular organoids (NMOs) via electrical pulse stimulation (EPS)","description":"This study aims at investigating the effects of electrical pulse stimulation (EPS) on the structural and functional maturation of human iPSC-derived neuromuscular organoids (NMOs). To characterise these effects on a molecular level, the transcriptomes of both EPS-treated and untreated NMOs at day 40 and day 60 were compared using bulk RNA sequencing.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001773","title":"Evaluation of the safety risk of hiPSC-derived cartilage: A pre-clinical study","description":"Although hiPSC-derived cartilage (hiPSC-Cart) showed potential for implantation to articular cartilage defects, toxicological and tumorigenic risks remain to be extensively assessed before clinical application. In this present study, in order to evaluate the safety risks of hiPSC-Cart and assure that the potential benefit outweighs the risks for the FIH (First-in-human) study, we have manufactured the hiPSC-Cart with clinically applicable process and conducted in vivo biodistribution and tumorigenicity studies using immunodeficient rat model.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001774","title":"Prefibrotic Bone Marrow Microenvironment is a Hallmark of Clonal Hematopoiesis","description":"Clonal hematopoiesis of indeterminate potential (CHIP) is linked to systemic inflammation and increased malignant risk, yet its impact on the bone marrow (BM) niche remains poorly understood. Through single-cell transcriptomic profiling of freshly isolated BM, we identify fibro-inflammatory rewiring as an early hallmark of CHIP. Beyond a myeloid-biased inflammatory state, CHIP BM exhibited coordinated TNFα activation across hematopoietic progenitor, monocyte, and stromal compartments. Stromal populations displayed early fibrotic remodeling, with mesenchymal and vascular cells upregulating collagen and extracellular matrix programs. Fibroblasts were markedly expanded independent of mutational subtype and acquired cancer-associated fibroblast (CAF)-like programs, rewiring niche interactions through IL-6, TGFβ, and collagen-integrin signaling. Together, these findings establish fibro-inflammatory BM remodeling as an early hallmark of clonal expansion, linking CHIP to prefibrotic stromal remodeling, immune dysregulation, and a niche architecture consistent with increased malignant risk.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-17T16:06:43.936194+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001775","title":"Whole Exome Sequencing of 66500 and 76709 samples","description":"This study includes whole-exome sequencing of two human samples to identify genetic variants associated with PRRT2-related disorders.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001776","title":"Whole Exome Sequencing of Non-Hodgkin Lymphoma Patients in Tabuk, Saudi Arabia","description":"This study presents whole exome sequencing (WES) data from 20 Non-Hodgkin \r\n  Lymphoma (NHL) patients. Samples represent diverse histopathological subtypes including Diffuse Large B-Cell Lymphoma (DLBCL), Follicular Lymphoma, and other NHL variants. Both nodal and extranodal disease origins are represented. Sequencing was performed to investigate the genomic landscape of NHL in a Saudi Arabian patient cohort.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[36831357],"external_links":null,"is_released":true,"released_date":"2026-06-05T11:54:31.699055+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001777","title":"Neo-CheckRay","description":"Patients with oestrogen receptor-positive (ER+), HER2-negative, early breast cancer (BC) have low pathological complete response (pCR) rates following neoadjuvant chemotherapy (NACT). Phase 3 trials showed that adding an anti-PD-1 immune checkpoint inhibitor (ICI) improves pCR, but there was less benefit in the PD-L1 negative tumours, characterised by an immune “cold” tumour microenvironment (TME). We hypothesized that immune-modulating stereotactic body radiation therapy (iSBRT) could enhance treatment response by reprogramming the immune deprived TME in early ER+/HER2- BCA. We conducted a phase 2, randomized, multicentre trial evaluating NACT plus iSBRT, with or without durvalumab (anti-PD-L1) and with or without oleclumab (anti-CD73) in 147 patients with high-risk, early, ER+/HER2- breast cancer patients.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-07T15:34:12.112634+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001778","title":"WES sequencing to characterize ALK","description":"This exome sequencing study aims to investigate the impact of the K1150dup mutation on lorlatinib progression and to explore potential therapeutic strategies to overcome resistance.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-05T16:20:46.818806+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001779","title":"RNA sequencing to characterize ALK","description":"ALK fusions are present in 3–5% of patients with non-small cell lung cancer (NSCLC). These fusions promote ligand-independent dimerization, resulting in constitutive activation of downstream signaling pathways, including RAS–MAPK and PI3K–AKT3. Here, we report the identification and characterization of the ALK in biopsies from a patient with ALK-positive NSCLC progressing on first-line lorlatinib","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-05T16:20:43.772812+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001780","title":"Expression profiles of DLL1 positive and negative subpopulations in metastatic colorectal cancer organoids under cetuximab treatment","description":"Bulk RNA sequencing was performed on metastatic colorectal cancer (mCRC) organoids subjected to cetuximab treatment and FACS-sorted according to DLL1 positivity. This study is part of a larger set of studies focused on investigating cetuximab induced populations in mCRC organoids","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-08T13:04:23.312426+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001781","title":"Biomarker analysis and treatment dynamics following preoperative ipilimumab plus nivolumab in locally advanced urothelial cancer from the phase 1B NABUCCO study","description":"In the current analysis of the full NABUCCO trial population (cohorts 1 and 2), we aimed to explore both potential biomarkers for response to combination ICB, as well as treatment dynamics to gain a better understanding of the effects of ICB on the urothelial cancer tumor microenvironment (TME).","abstract":null,"study_type":"RNASeq","pubmed_ids":[40489082],"external_links":null,"is_released":true,"released_date":"2026-05-21T12:31:47.844261+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001782","title":"Ex vivo drug screening identifies stromal APOL4 as a predictor of platinum sensitivity in cancers via immunomodulatory fibroblasts","description":"Despite initial high response rates to platinum-based therapy across solid tumors, most patients develop resistance. Studies have focused on tumor cell-intrinsic mechanisms, neglecting microenvironmental contributions to treatment outcomes. Through patient-derived ex vivo drug screening combined with integrated transcriptomic and single-cell profiling, we identify stromal Apolipoprotein L4 (APOL4) as a novel biomarker of platinum sensitivity. Functional screening revealed that APOL4 expression predominates in a specific cancer-associated fibroblast subtype (CAF-1) with distinctive matrix-remodeling and immunomodulatory properties. This CAF-1 subpopulation creates treatment-responsive microenvironments by enhancing metalloproteinase activities that facilitate immune cell infiltration. Stromal APOL4-enriched tumors showed increased immune infiltration and significantly improved clinical outcomes across multiple cohorts. Remarkably, our pan-cancer analysis of 33 tumor types demonstrated that CAF-1 enrichment consistently correlates with favorable immune profiles and improved survival. These findings establish ex vivo screening as a powerful discovery platform and identify stromal APOL4 as both a prognostic biomarker and key mediator of treatment response, highlighting the therapeutic potential of targeting immune-modulating fibroblasts to enhance platinum efficacy.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001783","title":"Long-read Nanopore and Ion Torrent sequencing data for BRCA1/2 variant detection","description":"This dataset contains long-read sequencing data generated using Oxford Nanopore Technologies for the analysis of BRCA1 and BRCA2 variants in individuals referred for hereditary breast cancer genetic testing. The study includes samples previously analyzed using Ion Torrent sequencing, enabling comparison between short-read and long-read sequencing approaches.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-12T15:41:27.167884+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001784","title":"Spatial functional genomics of assembloids identifies fibroblast states that organize epithelial aging niches","description":"This study defines a spatially organized fibroblast sate associated with epithelial aging niches by combining ovarian epithelial organoid-fibroblast assembloids with single-cell and spatial transcriptomes. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001785","title":"Human rectal biopsies to characterize the mast cell populations in healthy and IBS patients","description":"Human rectal biopsies have been subjected to scRNA-seq. The goal is to study, transcriptionally, cell populations of the human gut in healthy and IBS tissue. CD45 cells have been studied with a focus on the mast cell compartment. \r\n","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001786","title":"MPNST - WGS FASTQ","description":"Understanding the spatial and temporal dynamics of tumour evolution is crucial for determining the drivers of cancer progression. Here, we comprehensively profile a primary malignant peripheral nerve sheath tumour (MPNST) and its recurrence with a multi-omic and spatial approach at single-cell resolution. Leveraging the extensive heterogeneity in copy number aberrations (CNAs) as a native barcoding system, we fully resolve the evolutionary tree of this tumour revealing multi-furcations suggestive of ongoing chromosomal instability. We show gene dosage effects contribute to phenotypic diversity and are predominantly linear. Using laser capture microdissection, we performed spatial lineage tracing in a human tumour, elucidating the relationship between local expansions and interactions between tumour cells and the microenvironment.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-12T15:47:37.573199+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001787","title":"MPNST - 10X single nucleus RNAseq","description":"Understanding the spatial and temporal dynamics of tumour evolution is crucial for determining the drivers of cancer progression. Here, we comprehensively profile a primary malignant peripheral nerve sheath tumour (MPNST) and its recurrence with a multi-omic and spatial approach at single-cell resolution. Leveraging the extensive heterogeneity in copy number aberrations (CNAs) as a native barcoding system, we fully resolve the evolutionary tree of this tumour revealing multi-furcations suggestive of ongoing chromosomal instability. We show gene dosage effects contribute to phenotypic diversity and are predominantly linear with the exception of FOS in a specific subclone. Using laser capture microdissection, we performed spatial lineage tracing in a human tumour, elucidating the relationship between local expansions and interactions between tumour cells and the microenvironment.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-12T15:47:35.878271+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001788","title":"MPNST - DLPplus single nucleus DNAseq","description":"Understanding the spatial and temporal dynamics of tumour evolution is crucial for determining the drivers of cancer progression. Here, we comprehensively profile a primary malignant peripheral nerve sheath tumour (MPNST) and its recurrence with a multi-omic and spatial approach at single-cell resolution. Leveraging the extensive heterogeneity in copy number aberrations (CNAs) as a native barcoding system, we fully resolve the evolutionary tree of this tumour revealing multi-furcations suggestive of ongoing chromosomal instability. We show gene dosage effects contribute to phenotypic diversity and are predominantly linear with the exception of FOS in a specific subclone. Using laser capture microdissection, we performed spatial lineage tracing in a human tumour, elucidating the relationship between local expansions and interactions between tumour cells and the microenvironment.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-12T15:47:42.632291+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001789","title":"MPNST - LCM WGS FASTQ","description":"Understanding the spatial and temporal dynamics of tumour evolution is crucial for determining the drivers of cancer progression. Here, we comprehensively profile a primary malignant peripheral nerve sheath tumour (MPNST) and its recurrence with a multi-omic and spatial approach at single-cell resolution. Leveraging the extensive heterogeneity in copy number aberrations (CNAs) as a native barcoding system, we fully resolve the evolutionary tree of this tumour revealing multi-furcations suggestive of ongoing chromosomal instability. We show gene dosage effects contribute to phenotypic diversity and are predominantly linear. Using laser capture microdissection, we performed spatial lineage tracing in a human tumour, elucidating the relationship between local expansions and interactions between tumour cells and the microenvironment.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-12T15:47:40.948419+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001790","title":"MPNST - 10X single nucleus DNAseq","description":"Understanding the spatial and temporal dynamics of tumour evolution is crucial for determining the drivers of cancer progression. Here, we comprehensively profile a primary malignant peripheral nerve sheath tumour (MPNST) and its recurrence with a multi-omic and spatial approach at single-cell resolution. Leveraging the extensive heterogeneity in copy number aberrations (CNAs) as a native barcoding system, we fully resolve the evolutionary tree of this tumour revealing multi-furcations suggestive of ongoing chromosomal instability. We show gene dosage effects contribute to phenotypic diversity and are predominantly linear with the exception of FOS in a specific subclone. Using laser capture microdissection, we performed spatial lineage tracing in a human tumour, elucidating the relationship between local expansions and interactions between tumour cells and the microenvironment.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-12T15:47:39.264693+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001791","title":"MPNST - 10X Visium spatial transcriptomics","description":"Understanding the spatial and temporal dynamics of tumour evolution is crucial for determining the drivers of cancer progression. Here, we comprehensively profile a primary malignant peripheral nerve sheath tumour (MPNST) and its recurrence with a multi-omic and spatial approach at single-cell resolution. Leveraging the extensive heterogeneity in copy number aberrations (CNAs) as a native barcoding system, we fully resolve the evolutionary tree of this tumour revealing multi-furcations suggestive of ongoing chromosomal instability. We show gene dosage effects contribute to phenotypic diversity and are predominantly linear with the exception of FOS in a specific subclone. Using laser capture microdissection, we performed spatial lineage tracing in a human tumour, elucidating the relationship between local expansions and interactions between tumour cells and the microenvironment.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-12T15:47:34.109828+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001792","title":"Single-cell transcriptomics of intestinal myeloid cells in obese versus non-obese subjects","description":"The gut plays a central role in the development of metabolic diseases such as obesity and type 2 diabetes. Previous studies in mouse models of diet-induced obesity have revealed early intestinal inflammation. Several of these early inflammatory signatures observed in mice are thought to mirror aspects of human intestinal immune activation in obesity. To explore whether these similar patterns occur in humans, we used single-cell RNA sequencing to profile colon samples from obese and non-obese individuals.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001793","title":"Large-scale single-cell whole genome and transcriptome sequencing of normal esophagus epithelium","description":"This study utilizes SMART-PTA, a high-throughput workflow for joint single-cell whole-genome and whole-transcriptome sequencing, to map clonal evolution and phenotypic states in the human aging esophagus. By integrating single-cell phylogenies derived from whole-genome somatic variants with matched transcriptomic profiles, we reconstruct clonal dynamics at high resolution.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-27T15:18:58.589997+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001794","title":"Longitudinal ctDNA profiling in MGMT-silenced metastatic colorectal cancer, targeted methylseq","description":"cfDNA samples were used to construct EM-Seq (enzymatic converted methyl seq) libraries  The Twist Alliance Pan-cancer Methylation Panel (Twist Bioscience) was used for target enrichment with the Twist Targeted Methylation Sequencing Protocol.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001795","title":"Longitudinal ctDNA profiling in in MGMT-silenced metastatic colorectal cancer ctDNA exome","description":"This study elucidates how MGMT-silenced MSS colorectal cancers evolve under temozolomide and immunotherapy.  ctDNA was isolated from serially collected plasma samples at baseline, post-TMZ induction, during immunotherapy and, when available, at disease progression.  Changes in DNA sequence under these conditions were used to study which mutations may be driving tumour progression.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001796","title":"Longitudinal ctDNA profiling in in MGMT-silenced metastatic colorectal cancer ctDNA low pass whole genome","description":"We analyzed cfDNA fragmentomic profiles, focusing on transcription factor binding sites (TFBSs) as surrogates of chromatin accessibility. Therefore, we inferred the activity of 425 transcription factors, obtained previously by evaluating the coverage around their binding sites in all 95 cfDNA low-pass sequencing data.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001797","title":"RNA sequencing data of pediatric TCF3::PBX1 acute lymphoblastic leukemia","description":"TCF3::PBX1 leukemia is a rare subtype of B-cell acute lymphoblastic leukemia (B-ALL), occurring in approximately 3–5% of pediatric cases. It results from a chromosomal translocation t(1;19)(q23;p13), generating the TCF3::PBX1 fusion gene, which disrupts normal transcriptional regulation and contributes to leukemogenesis. Although historically associated with poor prognosis, contemporary risk stratification and intensified therapy have significantly improved outcomes, and both 5-years DFS and OS are nowadays ≥ 0.96.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-18T09:57:09.119491+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001798","title":"RNA sequencing data of pediatric BCR::ABL1 acute lymphoblastic leukemia","description":"The BCR::ABL1 fusion results from the t(9;22)(q34;11.2) translocation, also known as the Philadelphia chromosome. In children, BCR::ABL1-positive leukemia is rare, accounting for approximately 3% of cases. The BCR::ABL1 oncoprotein activates multiple signaling pathways that drive cell proliferation. Historically, this subtype was associated with an extremely poor prognosis; however, the incorporation of tyrosine kinase inhibitors into therapy has markedly improved outcomes, with overall survival now approaching 80% in pediatric patients. Relapse most commonly occurs through the emergence of clones harboring kinase domain mutations, yet 30–40% of relapses arise in the absence of such mutations, a phenomenon that remains poorly understood.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-18T09:57:12.356887+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001799","title":"RNA sequencing data of pediatric KMT2A-rearranged acute lymphoblastic leukemia","description":"Pediatric KMT2A-rearranged leukemia is an aggressive subtype of leukemia commonly seen in infants (less tha 1 year old) and young children. It involves rearrangements of the KMT2A gene (formerly MLL) on chromosome 11q23, resulting in fusion genes that drive uncontrolled cell growth. This subtype is most often found in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) and is associated with a poor prognosis. In infants, the 5-year event-free and overall survival rates are around 35–40%. Despite intensive chemotherapy, outcomes remain challenging, prompting ongoing research into targeted therapies and novel treatment strategies.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-18T09:57:15.592786+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001800","title":"RNA sequencing data of pediatric T-cell acute lymphoblastic leukemia","description":"T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy accounting for approximately 15–25% of pediatric and adult ALL cases. Despite significant therapeutic improvements over the last decade, the prognosis of T-ALL remains less favorable than that of B-ALL, with 5-year EFS and OS of around 76–82% and 80–88%, respectively, depending on the treatment protocol used. T-ALL patients often suffer from failure of induction therapy or early relapse, which is associated with a dismal prognosis. Approximately 10–15% of T-ALL patients experience relapse, and survival after relapse is poor.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-18T09:57:20.460931+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001801","title":"RNA sequencing data of pediatric ETV6::RUNX1 acute lymphoblastic leukemia","description":"ETV6::RUNX1 (E::R) subgroup is the second most frequent form of B cell acute lymphoblastic leukemia (B-ALL) in childhood. This subgroup of ALL generally presents with low-risk features and responds well to chemotherapy with ensuing favorable prognosis. Some patients, however, have a slow response to induction treatment and carry increased risk for relapse.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-18T09:57:25.327408+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001802","title":"RNA sequencing data of pediatric hyperdiploid acute lymphoblastic leukemia","description":"The hyperdiploid (HeH) subtype with 51–67 chromosomes is the most common subtype in childhood, presented in 25–30% of the cases, and is associated with excellent prognosis . The HeH subtype harbors relatively few additional genetic alterations, suggesting that extra chromosomes are the driving event for leukemia onset. Secondary hits usually affect the RAS signaling pathway and histone modifiers.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-18T09:57:33.448313+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001803","title":"RNA sequencing data of pediatric B-other acute lymphoblastic leukemia","description":"For a long time, approximately 70% of childhood B-ALL cases could be classified routinely, and the remaining 30% were classified into the “B-other” group lacking the known genetic features. However, more recently, new genomic tools have uncovered new subtypes among the B-other groups. Approximately 10% of B-ALL cases lack the recurrent genetic abnormalities, and are referred as \"B-other\". They are typically more heterogeneous than other subtypes of B-ALL, and their prognoses are more variable. In a more recent update of the B-ALL classification, 27 subtypes were identified (Arber et al., 2022). The identification of some of these subtypes is dependent on NGS methods, such as RNA sequencing, which are not routinely used in all clinical laboratories. For example, ETV6::RUNX1-like and DUX4-rearranged subtypes have been identified using RNA sequencing. For this study, subtype predictions for some of the cases were acquired by using the ALLIUM (Krali et al., NPJ Precis Oncol., 2023) and ALLCatchR (Beder et al., Blood, 2022) tools for the RNA sequencing data.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-18T09:57:41.658379+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001804","title":"Epigenetic characterization of glioblastoma stem cells","description":" Chromatin accessibility discriminates stem from mature cell populations, enabling the identification of primitive stem-like cells in primary tumors, such as glioblastoma (GBM) where self-renewing cells driving cancer progression and recurrence are prime targets for therapeutic intervention. We show, using single-cell chromatin accessibility, that primary human GBMs harbor a heterogeneous self-renewing population whose diversity is captured in patient-derived glioblastoma stem cells (GSCs). In-depth characterization of chromatin accessibility in GSCs identifies three GSC states: Reactive, Constructive, and Invasive, each governed by uniquely essential transcription factors and present within GBMs in varying proportions. Orthotopic xenografts reveal that GSC states associate with survival, and identify an invasive GSC signature predictive of low patient survival, in line with the higher invasive properties of Invasive state GSCs compared to Reactive and Constructive GSCs as shown by in vitro and in vivo assays. Our chromatin-driven characterization of GSC states improves prognostic precision and identifies dependencies to guide combination therapies.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[33427645],"external_links":null,"is_released":true,"released_date":"2026-06-11T17:32:51.830674+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001805","title":"Genomic characterization of upper urinary tract urothelial carcinoma and clonal evolution of intravesical recurrences","description":"Patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical surgery are at high risk of developing intravesical recurrences (IVR). Molecular correlates of IVR after UTUC surgery are poorly understood, while therapeutic targets for UTUC and diagnostic markers for IVR are lacking. Here, we performed targeted DNA-sequencing on 514 tumor samples to characterize the genomic landscape of 414 UTUC and assess clonal evolution in 104 paired UTUC-IVR.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001806","title":"RNA sequencing data of pediatric hypodiploid acute lymphoblastic leukemia","description":"Hypodiploid acute lymphoblastic leukemia (ALL) is a rare subtype of B-cell ALL characterized by chromosome number < 45 , encompassing near-haploid (24–29 chromosomes) and low-hypodiploid (30–39 chromosomes) subgroups. These subgroups display distinct genetic landscapes, including Ras and receptor tyrosine kinase pathway alterations in near-haploid ALL, and frequent IKZF2, RB1, and germline TP53 alterations in low-hypodiploid ALL. Clinically, hypodiploid ALL is associated with dismal prognosis, with 5-year overall survival rates often between 50-70% in children and markedly worse in adults. Despite advances in risk stratification and MRD-guided therapy, allogeneic stem cell transplantation remains the current standard recommendation for affected patients.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-18T09:57:51.407421+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001807","title":"Improving Variant Detection and Transcriptomic Alignment Accuracy for Acute Lymphoblastic Leukaemia Patients: A Pan-Genome Graph Approach","description":"Construct a Acute Lymphoblastic Leukaemia specific spliced pangenome graph anchored to the GRCh38 reference genome and enriched with transcript annotations and variants associated with ALL to enhances transcriptomic alignment accuracy and variant detection in ALL patients","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-04T15:36:19.031749+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001808","title":"Integrated Single-Cell and Microbiome Profiling of Stable Bronchiectasis Across Disease Severity","description":"Bronchiectasis is a chronic respiratory disease characterized by persistent airway inflammation and recurrent infections. In this study, sputum samples from patients with mild, moderate, and severe bronchiectasis, collected during clinically stable disease, were analyzed using flow cytometry, single-cell RNA sequencing, and 16S rRNA gene sequencing. The resulting datasets enable characterization of neutrophil populations, transcriptional states, and airway microbial communities across disease severity stages.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-28T14:34:30.362091+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001809","title":"Genome-wide association study of never-smoking non-drinking young adults developing oral squamous cell carcinoma","description":"This study aims to evaluate if rare germline variants are associated with never-smoking non-drinking young adults oral squamous cell carcinoma.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-28T15:16:07.560395+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001810","title":"C1q+ TAMs mediate immunosuppression in GBM","description":"Analysis of fresh GBMs and patient-derived tumor tissue cultures treated with IgG or anti-LIF by RNAseq, single-cell RNAseq and spatial transcriptomics to study the immune tumor microenvironment and the role of LIF in regulating C1q+ TAMs.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001811","title":"SV-based ctDNA detection in soft tissue sarcoma","description":"33 patients with localized soft tissue sarcoma consented for ctDNA tracking in the peri-operative and surveillance periods. WGS at a target of 15x coverage was performed from DNA extracted from FFPE of localized soft tissue sarcoma. Structural variants were identified from WGS and ddPCR assays were designed for tumor informed tracking of SV for ctDNA. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-28T14:54:19.938408+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001812","title":"Single-cell profiling of patient-derived ovarian cancer organoids identifies a tamoxifen resistance state with translational relevance in breast cancer","description":"Tamoxifen is a selective estrogen receptor modulator used primarily in hormone receptor-positive breast cancer, but its biological activity and determinants of response in ovarian cancer remain incompletely defined. Patient-derived organoid (PDO) models combined with single-cell transcriptomics may resolve tumor-intrinsic transcriptional states associated with endocrine response.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001813","title":"Whole exome sequencing of mesothelioma FFPE tumors and paired samples. ","description":"This study focus on the genomic alterations occurred on the exonic regions for mesothelioma.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001814","title":"WES and RNA sequencing of mesothelioma patients from CONFIRM clinical trial","description":"CONFIRM is a placebo controlled, double-blind randomised phase III clinical trial designed to investigate the efficacy of the anti-PD1 inhibitor nivolumab in patients with relapsed mesothelioma. This study applied the whole exome sequencing and transcriptomic sequencing to uncover determinants of efficacy in patients exhibiting the most extreme response outcomes. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[40691143],"external_links":null,"is_released":true,"released_date":"2026-05-29T15:24:16.337393+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001815","title":"Comparative transcriptomics reveal molecular convergence and divergence in parkinsonian disorders","description":"Elucidate the biological convergence and divergence across the parkinsonian spectrum. The study contains data processed at two different sites as well as Alzheimer's disease as an non-parkinsonian control. Specifically, Parkinson's disease (PD, N=448), dementia with Lewy bodies (DLB, N=80), multiple system atrophy (MSA, N=35), progressive supranuclear palsy (PSP, n=42), corticobasal degeneration (CBD, n=17), Alzheimer's disease (AD, N=72) and neurologically healthy controls (N=283). RNA-seq was carried out using ribosomal depletion.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[42052893],"external_links":null,"is_released":true,"released_date":"2026-05-08T12:02:45.576713+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001816","title":"Epithelial states co-determined by YAP associated fetal programming and WNT signaling in colorectal cancer","description":"To further investigate epithelial cell states and expand the available colorectal cancer dataset, we generated single-cell RNA-sequencing data from healthy and primary tumor samples obtained from 18 colorectal cancer patients.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001817","title":"Resistance to anti-BCMA T-cell-redirecting therapy","description":"We applied whole-genome sequencing (WGS) to MM cells from cohorts of 102 relapsed patients treated with anti-BCMA CAR T and TCE therapies","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-28T14:27:09.405583+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001818","title":"Multi-omics datasets (WES, RNA-seq) of mesothelioma MIST4 study, a phase II PD-L1/VEGF blockage clinical trial","description":"This study comprises 26 mesothelioma patients with whole exome and RNA sequencing, designed to examine the efficacy and correlates of response to dual inhibition of programmed death-ligand 1 and vascular endothelial growth factor inhibition.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[39168966],"external_links":null,"is_released":true,"released_date":"2026-05-29T15:24:21.92188+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001819","title":"Microbiome of very preterm infants","description":"This is microbial data from an observational cohort study examining the gut microbiome of very preterm infants (born before 30 weeks gestation and/or under 1000g birth weight) admitted to a level IV NICU in the Netherlands.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001820","title":"Staufen1 regulates human erythropoiesis via post-transcriptional control of iron transport","description":"This study aims to define the role of the double-stranded RNA-binding protein STAU1 in human erythropoiesis and its relevance to dyserythropoiesis in myelodysplastic syndromes. We investigate how altered STAU1 expression affects erythroid differentiation, red cell output, and long-term erythroid potential using primary human CD34+ hematopoietic stem and progenitor cells, MDS samples, and xenograft models. A key goal of the project is to identify the transcriptomic and post-transcriptional programs regulated by STAU1 during erythroid development. ","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001821","title":"Carcinoma of Unknown Primary (CUP): A comparison across tissue and liquid biomarkers (CUP-COMP) study","description":"The Carcinoma of Unknown Primary (CUP): A comparison across tissue and liquid biomarkers (CUP-COMP) study (NCT: NCT04750109) was sponsored by The Christie NHS Foundation Trust and funded by Innovate UK.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-08T10:07:32.805758+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001822","title":"Multi-omics datasets (WES, RNA-seq) of mesothelioma MIST1 study, a phase II PARP inhibitor (rucaparib) clinical trial","description":"This study comprises 26 mesothelioma patients with whole exome and RNA sequencing.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001823","title":"Multi-omics datasets (WES, RNA-seq) of mesothelioma MIST2 study, a phase II CDK4/6 (abemaciclib) clinical trial","description":"This study comprises 26 mesothelioma patients with whole exome and RNA sequencing, to to assess potential sensitivity to CDK4/6 inhibition in p16ink4A-negative mesothelioma.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[35157829],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001824","title":"Multi-omics datasets (WES, RNA-seq) of mesothelioma MIST7 study, a phase II PARP+PD1 inhibition clinical trial","description":"This study comprises 26 mesothelioma patients with whole exome and RNA sequencing, aimed to access niraparib and dostarlimab efficacy in patients with platinum-sensitive relapsed mesothelioma.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001825","title":"Multi-omics datasets (WES, RNA-seq) of mesothelioma NERO study, a phase II PARP inhibitor clinical trial","description":"Niraparib Efficacy in Patient With Unresectable Mesothelioma, NERO, this randomised phase II trial is designed to evaluating the efficacy of the PARP inhibitor Niraparib versus active symptom control.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[37993149],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001826","title":"Spatial resolved sequencing to explore epithelioid to sarcomatoid transition and evolution","description":"There are three main histological subtypes of mesothelioma epithelioid, biphasic and sarcomatoid, which represents different cell status of mesothelioma. We applied Nanostring DSP transcriptome and whole exome sequencing to provide new sights to the mechanism of E to S transition and evolution.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001827","title":"Mitochondrial peroxiredoxin 3 is a tractable cancer therapeutic target modulated by SLC7A11","description":"This study is aimed at elucidating the anti-tumor mechanism and therapeutic potential of the PRX3 inhibitor thiostrepton in mesothelioma by investigating its effects on mitochondrial redox homeostasis, oxidative stress–induced apoptosis, and tumor suppression in preclinical and clinical settings. Mesothelioma explants are treated with thiostrepton and subjected to RNA sequencing under baseline, untreated control, and thiostrepton-treated conditions to characterize treatment-induced transcriptional alterations and identify molecular pathways associated with therapeutic response and resistance.\r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-20T09:58:24.537835+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001828","title":"RNA sequencing dataset of explants from mesothelioma patients for SLC7A11 study","description":"This study is aimed at elucidating the mechanism of PRX3 inhibitor (thiostrepton) for mesothelioma by investigating its disruption of mitochondrial redox homeostasis, induction of apoptosis, and therapeutic efficacy in preclinical models and early-phase clinical settings, as well as identifying SLC7A11 as a key mediator of resistance and a potential combinatorial target.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001829","title":"T-ALL RNA-Seq raw data files for ALLCatchR2","description":"Bone marrow or peripheral blood samples were collected of adult patients at first diagnosis of T-precursor acute lymphoblastic leukemia. RNA was isolated from mononuclear cells and subjected to mRNA library prep using Poly-A selection and sequencing on a NovaSeq 6000 system. Obtained gene expression profiles and gene fusion calls were used to allocate samples to molecular disease subtypes.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-28T15:31:50.362034+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001830","title":"Studying ctDNA signal in plasam whole genome sequencing from high risk Breast Cancer patients","description":"We apply fragmentomics and minimal residue disease tools to find out signals from ctDNA in high risk Breat Cancer patients.\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-05T17:42:45.216959+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001831","title":"RNAseq of colon cancer patients (integration with HPTM analyses)","description":"The aim of this study is to define gene expression differences between tumor and matched normal tissues in patients with colon cancer using RNA sequencing. By comparing paired samples, we seek to identify tumor-specific transcriptional programs and recurrently dysregulated pathways associated with disease development. Additionally, this dataset is intended to provide a resource for exploring molecular heterogeneity across patients and for supporting the discovery of clinically relevant biomarkers and therapeutic targets.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001832","title":"RAF1 extrachromosomal DNA amplification confers acquired erlotinib resistance in NSCLC cell model","description":"Despite their clinical significance, EGFR-directed therapies inevitably encounter drug resistance. This study demonstrates that ecDNA-mediated RAF1 amplification reactivates MAPK signaling independently of mutant EGFR, contributing to erlotinib resistance in EGFR-mutant NSCLC cell models. This finding identifies oncogenic amplification by ecDNA as a novel mechanism leading to erlotinib resistance, opening new avenues for therapeutic strategies in NSCLC.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-08T14:46:44.746367+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001833","title":"Comprehensive Genomic Profiling of a National Cohort of Pediatric Papillary Thyroid Carcinoma in Hungary","description":"Pediatric papillary thyroid carcinoma (PTC) is a rare childhood malignancy with increasing incidence and distinct clinicopathological features, including high rate of locoregional metastases and different molecular background compared to adult cases. Traditional treatments (surgery, radioactive iodine) are effective but pose long-term risks, prompting the exploration of targeted therapies. We performed comprehensive genomic profiling on 21 pediatric PTC patients utilising the Illumina TruSight Oncology 500 platform and detected mutations, gene fusions, copy number variations and revealed tumor mutational burden. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-27T12:45:21.079792+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001834","title":"bulkTCR-seq of CD4+ T cells from lymph nodes and tumors of NSCLC patients","description":"This study explore the CD4+ T cells clonality in paired lymph nodes and tumors of 5 different NSCLC patients.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-21T16:15:00.763187+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001835","title":"bulkRNA-seq of CD4+ T cells from lymph nodes and tumors of NSCLC patients","description":"This study explore the CD4+ T cells diversity in paired lymph nodes and tumors of 5 different NSCLC patients.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-21T16:15:00.763187+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001836","title":"scTCR-seq of CD4+ T cells from blood, lymph nodes and tumors of NSCLC patients","description":"This study explore the CD4+ T cells clonality in paired blood, lymph nodes and tumors of 3 different NSCLC patients. After FACS-sorted of Tregs (DAPI- CD45+ CD4+ CD25hi CD127lo) and Tconvs (DAPI- CD45+ CD4+CD25lo CD127lo/hi), cells were mixed in equal proportion (fifty/fifty ratio) and processed with 10X Chromium (10X Genomics) immunoprofiling kit (2 bloods, 4 lymph nodes and 3 tumors) and sequenced using Illumina platforms.\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-05-21T16:15:00.763187+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001837","title":"Cell-free DNA fragmentome profiles predict immunotherapy response","description":"Mutation-based liquid biopsy approaches face challenges in accurately identifying the cellular origin of variants, which complicates the determination of circulating tumor DNA (ctDNA) molecular response. We hypothesized that these limitations could be addressed by utilizing genome-wide cell-free DNA (cfDNA) fragmentome methods. To this end, we performed whole-genome sequencing of 528 serial cfDNA samples and quantified the cfDNA tumor fraction (TF) using DELFI-TF, a tumor- and mutation-naive machine learning cfDNA fragmentome classifier, across two prospective clinical protocols for immunotherapy-treated non-small cell lung cancer (NSCLC). DELFI-TF values were validated independently by hybrid capture fixed gene panel next-generation sequencing, and the landmark cfDNA fragmentome molecular response (fMR) was determined within 3-9 weeks from the initiation of immunotherapy. Individuals with fMR attained significantly longer progression-free and overall survival than those without fMR (logrank p=2.7e-14 and p=3e-9), including in patients with mutation-based molecular progression (logrank p=1.2e-4 and p=2e-3). Our findings suggest that analyses of the cfDNA fragmentome can provide a clinically meaningful measure of circulating tumor fraction and validate the clinical sensitivity of plasma-only cfDNA fragmentome-based molecular response as an early indicator of immunotherapy response. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-10T17:00:40.487632+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001838","title":"WGS on matched blood samples for SU2C GSC WGS data.","description":"Matched blood samples for SU2C GSC WGS data, corresponding to samples new to Owen Whitley's 2nd data chapter for PhD thesis and not present in Richards et al. 2021 set (EGAS00001004395). These samples were collected as part of a multi-omic characterization of cancer stem cells, in order to allow mutation calling for cancer stem cell lines collected from matched patients. Since many of these samples are matched to RNA-seq, DNA methylation arrays, and ATAC-seq data from Owen Whitley's PhD thesis (2022, University of Toronto), correlative analyses can be performed between mutational features and other -omics data, allowing a more holistic understanding of GSC biology than single datatype analyses. Please contact Peter Dirks' lab for more information.\r\n\r\nNote the following: 1) BT248_L was derived from a recurrent tumour from the same patient corresponding to BT189_L, and so sample BT248_B (derived from the blood of the BT248 patient) can be used as a \"normal\" reference for BT189_L. 2) G691_L is derived from a recurrent tumour for the same patient as G620_L, and so G620_B (blood derived reference sample for G620_L, cohort 1, from Richards 2021 Nature Cancer paper, EGAS00001004395) can be used as a \"normal\" reference for G691_L. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001839","title":"Single-molecule nanopore sequencing of plasma and cerebrospinal fluid cell-free DNA from paediatric patients with brain and extracranial solid tumours.","description":"Cell-free DNA (cfDNA) profiling enables minimally invasive cancer detection and monitoring. \r\nHere, we report single-molecule nanopore sequencing data generated using the SIMMA assay for 792 plasma and cerebrospinal fluid cfDNA samples from 277 paediatric patients with diverse brain and extracranial tumours. SIMMA is a low-input single-molecule sequencing approach that enables multimodal whole-genome and high-depth targeted sequencing of the same cfDNA sample for both tumour-agnostic and tumour-informed liquid biopsy analysis (Sauer et al. 2026). ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-07T09:16:20.056668+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001840","title":"Targeted FOXP3-TSDR demethylation for de novo induction and functional stabilization of antigen-specific regulatory T cells","description":"This submission comprises RNA sequencing of primary human CD4⁺ memory conventional T cells analyzed to assess the effect of targeted FOXP3-TSDR epigenetic editing. Samples were collected at day 21 post-transfection and include cells exposed to the epigenetic editor together with either FOXP3-TSDR-targeting guide RNAs (sgTSDR) or a non-targeting guide RNA control (sgNon). The main experimental variable under investigation is targeted FOXP3-TSDR demethylation and its impact on the broader DNA methylation landscape.\r\n\r\nBiological replicates from independent human donors are included for each condition (n = 4 per condition). The sgNon group serves as the principal control condition for comparison with sgTSDR-edited samples. Additional reference samples such as mock-electroporated CD4⁺ memory T cells and expanded regulatory T cells (Tregs) provide baseline and lineage-reference methylation profiles.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001841","title":"Treatment of T cells with the STING inhibitor H151","description":"T cells from healthy human donors were activated with CD3/CD28 beads and IL-2 alone or in presence of the STING inhibitor H151 to assess effects on T cell function.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001842","title":"Virome Lifelines Next","description":"This dataset includes virus-like particle–enriched metagenomic sequencing data from 1,110 fecal samples, collected from 315 mother–infant pairs in the Lifelines NEXT cohort, and generated between 2022 and 2023.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-19T09:41:20.149383+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001843","title":"Early-life gut microbiome development in preterm infants: the NutriBrain clinical trial","description":"Metagenomic sequencing data were generated from fecal samples collected from preterm infants enrolled in the NutriBrain clinical trial, a study investigating the impact of early-life nutritional supplementation on gut microbiome development and neurodevelopmental outcomes. Samples were obtained longitudinally during the neonatal period under standardized collection protocols, and total microbial DNA was extracted and subjected to high-throughput shotgun sequencing. The study aims to improve understanding of the relationship between neonatal nutrition, microbiome maturation, and infant health outcomes.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-08T10:49:51.350859+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001844","title":"Neutrophil myeloperoxidase as a functional biomarker for RSV severity: implications for in vitro therapeutic screening","description":"This study investigates gene expression profiles in neutrophils from healthy adult donors using RNA sequencing. The aim is to define baseline transcriptional variation in circulating neutrophils. Samples were collected from peripheral blood and processed under standardised conditions. The dataset provides a reference for studies of immune function and inflammatory disease.\r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-04T12:52:17.649863+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001845","title":"Whole genome and transcriptome sequencing of cancer of unknown primary tumours","description":"Genome sequencing of cancer of unknown primary tumours were used to determine yield of clinical biomarkers for a molecular guided trial or for resolving cancer type of origin. This study includes profiling of germline DNA and tumour DNA by whole genome sequencing of tissue biopsies. This study also includes profiling of tumour RNA by whole transcriptome sequencing.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001846","title":"Metastatic prostate cancer subtyping using 5-hydroxymethylcytosine sequencing of cell-free DNA","description":"The project aims to investigate cfDNA to tissue concordance and develop non-invasive subtype classifiers. Our work lays the foundation for a robust, non-invasive approach to subtype classification and disease monitoring, offering insights into prostate cancer progression and potential avenues for precision medicine. We are uploading the fastq files in this study. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001847","title":"Plasma cfMeDIP-seq profiling of recurrent IDH-mutant glioma patients treated with olaparib and durvalumab in the SOLID trial","description":"Plasma cfMeDIP-seq data from recurrent IDH-mutant glioma patients treated with olaparib and durvalumab in the SOLID phase II trial. Longitudinal plasma cfDNA methylome profiles were generated to identify circulating methylation signatures associated with treatment response and progression-free survival.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001848","title":"Transcriptome analysis of mesothelioma tumor samples in MEDUSA cohort","description":"MEDUSA, mesothelioma evolution: deciphering drugable Somatic alterations, aimed at infer a human evolutionary model of MPM tumorigenesis and understand the inter-relationships that exist between genomic ITH, host immune surveillance and clinical phenotype, as well as providing a platform for deriving preclinical models to underpin pharmacogenomic investigations.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001849","title":"Developmental state shapes EWS::FLI1 fusion oncogene effects during human mesenchymal differentiation","description":"The project aimed to define how developmental state shapes EWS::FLI1 activity by generating a time‑resolved single‑cell RNA‑seq atlas of human pediatric mesenchymal stem cell differentiation. Cells were profiled in four lineage trajectories (adipogenic, chondrogenic, osteogenic, and neurogenic) at daily resolution with and without controlled induction of EWS::FLI1 expression. Using droplet‑based scRNA‑seq of hpMSC spheroids from pooled juvenile donors, we achieved high temporal and lineage resolution. This dataset provides a high‑resolution transcriptional framework to quantify how EWS::FLI1 perturbs mesenchymal differentiation over developmental time.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001850","title":"Transcriptional profiling of monocyte-derived dendritic cell differentiation in systemic lupus erythematosus","description":"This project investigates transcriptional and regulatory changes associated with dendritic cell differentiation in systemic lupus erythematosus (SLE). Peripheral blood monocytes from Mexican women with SLE and healthy controls were differentiated in vitro into monocyte-derived dendritic cells (moDCs) and tolerogenic dendritic cells (tolDCs). The study aims to characterize interferon-associated signatures, identify pathways involved in immune tolerance dysfunction, and investigate regulatory networks associated with SLE pathophysiology.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001851","title":"Beta hydroxybutyrate alters beta cell identity and function in human islets","description":"Fasting alters insulin secretion in humans and islet cell composition in mice. Fasting triggers ketogenesis, which increases beta hydroxybutyrate (BHB) levels. BHB is a signaling molecule that alters insulin secretion in primary islets. We hypothesized that BHB alters human islet cell composition and identity. Primary human islets were cultured with R-BHB or its non-metabolizable enantiomer, S-BHB. Human islets cultured with R-BHB, but not S-BHB, resulted in an increased C-peptide-glucagon+ to C-peptide+glucagon- cell ratio, and an increased frequency of C-peptide+glucagon+ bihormonal cells and NKX6.1+glucagon+ cells. Single-cell transcriptomics revealed upregulation of alpha cell identity genes in R-BHB treated islet beta cells. Alterations in beta cell identity were accompanied by increased basal insulin secretion in response to low glucose, and a reduced insulin stimulation index in response to high glucose. The differential effects of the two BHB enantiomers on islet cell composition indicated that ketone metabolism is involved in islet cell identity change. Supporting this hypothesis, a subpopulation of beta cells in islets treated with R-BHB characterized by low ketolysis genes, OXCT1 and ACAT1, did not show altered alpha and beta cell identity genes. Additionally, primary islets from type 2 diabetes donors, which exhibited reduced OXCT1 and ACAT1 expression relative to donors without diabetes, did not display altered islet cell composition and beta cell function from R-BHB treatment. Our findings uncover a novel role of BHB in modulating beta cell identity, with potential implications for islet function in states with chronically elevated ketone concentrations.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-03T12:28:27.285246+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001852","title":"A gene expression signature enables metastatic risk stratification of low-risk cutaneous squamous cell carcinoma patients","description":"Cutaneous squamous cell carcinoma (CSCC) is among the most common cancers, with an annual increase in incidence of 2–6%. While most primary CSCCs are curable through surgery, 2-5% of patients develop metastases. Current staging systems are insufficient to accurately stratify patients for metastasis, as more than one-third of patients who develop metastasis are initially classified as low-risk (BWH stage T1/T2a). Existing gene expression signatures for predicting metastases were developed in cohorts enriched in higher T-stages, comprised a low number offor higher T-stages, had few metastatic events, and lacked independent validation. Here, we aimed to develop a gene expression model to better stratify CSCCs by metastatic risk, particularly in the largest patient group (stage T1/T2a), which accounts for about 90% of the entire CSCC population.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001853","title":"Transcriptomic profiling of human primary pulmonary artery endothelial cells before and after over-expression of KLF factors","description":"Transcriptomic profiling using RNA-seq of human primary pulmonary artery endothelial cells before and after over-expression of KLF factors","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-17T09:36:26.713629+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001854","title":"Spatial Transcriptomics of Pulmonary Vascular Remodelling in IPAH","description":"This study uses NanoString GeoMx Digital Spatial Profiling to investigate spatial transcriptomic changes in pulmonary vessels from idiopathic pulmonary arterial hypertension (IPAH) lungs compared with healthy controls. FFPE lung tissue sections from 5 IPAH patients and 6 control donors were profiled to identify disease-associated molecular pathways and cellular programs involved in pulmonary vascular remodeling.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-17T12:58:29.997741+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001855","title":"Modulation of H3K27me3 by Tazemetostat EZH2 inhbition in cell line models","description":"Three genetically distinct neurobalstoma celll line models were treated for 21 days with DMSO control or Tazemetstat, followed by H3K27me3 or EZH2 ChIP-seq and bulk RNA-seq","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001856","title":"Histone epigenetics of neuroblastoma patient tumour samples","description":"In this study, we aimed to comprehensively investigate the role of H3K27me3 in neuroblastoma tumourigenesis and clinical heterogeneity. In this dataset 29 neuroblastoma patient tissue biopsies were analysed for H3K27me3, H3K27ac ChIP-seq in addition to bulk RNA-seq for 5 of the samples.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001857","title":"H3K27me3 analysis of 18 neuroblastoma cell lines","description":"In this study, we aimed to comprehensively investigate the role of H3K27me3 in neuroblastoma tumourigenesis and clinical heterogeneity. In this dataset 18neuroblastoma cell lines were analysed for H3K27me3 ChIP-seq. ","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001858","title":"Perturb Seq CRISPR reactivation screen","description":"In SK-N-AS cell line, 100 target genes were re-acitvated using dCAS9-VPR with the aim of one target gene per cell.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001859","title":"PCBP1 splicing signature","description":"We studied patients with rare loss-of-function variants in PCBP1. We collected blood samples for 5 patients in order to perform short-term lymphocyte cultures to study splicing signature. PCBP1 is a protein involved in the regulation of alternative splicing. Using a comparison of 5 patients versus 49 controls we found a strong signature involving exon skipping.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-15T10:11:22.417308+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001860","title":"Multi-omics analysis revealed clonal evolution of the sarcoma patient-derived xenograft","description":"We performed whole-exome sequencing and RNA-seq of sarcoma PDXs, along with their matched original tumors when available.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-19T15:45:42.851703+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001861","title":"Randomized trial of citrulline administration in patients hospitalized in intensive care for COVID-19 acute respiratory distress syndrome","description":"Respiratory involvement from SARS-CoV-2 leads to ARDS and significant immunosuppression (lymphopenia), exposing patients to prolonged ventilation and late mortality related to the acquisition of nosocomial infections.\r\nThe lymphopenia characteristic of severe forms of ARDS secondary to SARS-CoV-2 infection may be linked to the expansion of MDSCs and arginine depletion in lymphocytes.\r\nFurthermore, severe forms of COVID-19 pneumonia are marked by persistent ARDS with the acquisition of nosocomial infections, as well as by prolonged lymphocyte dysfunction associated with the emergence of MDSCs.\r\nCorrecting hypoargininemia could be an effective therapy to rapidly correct lymphocyte dysfunction, reduce the acquisition of ICU-acquired infections, and accelerate respiratory clearance of the virus.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-30T15:14:37.491073+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001862","title":"Somatic mitochondrial DNA variants in hepatocellular carcinoma","description":"Study description: Hepatocellular carcinoma (HCC) is among the most common primary liver malignancies, and somatic alterations of the mitochondrial genome have been reported across multiple tumour types, including HCC, but their frequency, spectrum, and clinical relevance remain incompletely characterised. This study was designed as an independent validation cohort for findings obtained from analysis of TCGA-LIHC data, with the aim of systematically cataloguing somatic mitochondrial DNA (mtDNA) variants in HCC and assessing their recurrence, functional distribution across mtDNA loci, and heteroplasmy levels. A paired tumour / non-tumoral tissue design was used to allow somatic events to be distinguished from germline variation and from inter-individual heteroplasmic background. Surgically resected HCC specimens and matched adjacent non-tumoral liver tissue were obtained from 36 consecutive patients treated at IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy. The resulting dataset is intended to support reuse for cross-cohort comparisons of mtDNA mutational landscapes in liver cancer.\r\n\r\nDataset title: Targeted mitochondrial genome paired-end MiSeq sequencing of 72 matched HCC and non-tumoral liver tissue samples\r\nDataset description: This dataset comprises paired-end FASTQ files (two files per sample, R1 and R2) from targeted mitochondrial genome sequencing of 72 human samples: 36 surgically resected hepatocellular carcinoma tissues and their 36 patient-matched adjacent non-tumoral liver tissues. Mitochondrial DNA was enriched by long-range PCR using overlapping amplicon sets spanning the full 16.6 kb mitochondrial genome, supplemented by additional targeted amplicons covering regions of low coverage identified in a pilot experiment. Sequencing libraries were prepared with the Illumina Nextera XT DNA Library Preparation Kit using IDT for Illumina UD Indexes and sequenced on an Illumina MiSeq instrument with the MiSeq Reagent v2 500-cycle kit in 2 × 250 bp paired-end mode. All samples are derived from Homo sapiens; the dataset contains exclusively mtDNA-targeted reads, and no germline whole-genome or whole-exome data are included.","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001863","title":"Probiotics and the EARly Life effects on intestinal bacteria and inflammation in children with Cystic Fibrosis (The “PEARL-CF” Study)","description":"The role of probiotics in children with cystic fibrosis (CwCF) remains unclear. The PEARL-CF study was an international, double-blind, randomized, placebo-controlled study involving CwCF (0–6 years), and assessed the effects of a probiotic on intestinal microbiota and clinical outcomes. A multi-strain probiotic (15 Lactobacillus/Bifidobacterium strains; ∼2-3×1010 CFU daily) or placebo was administered for 12-months and participants followed a further 12-months post-intervention. ","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-04T11:10:03.037872+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001864","title":"Parallel in-depth analysis of repeat expansions: an updated Clin-CATS workflow for nanopore R10 flow cells","description":"Hereditary ataxias, caused by expansions of short tandem repeats, are difficult to diagnose using traditional PCR and Southern blot methods, which struggle to detect complex repeat expansions and cannot assess repeat interruptions or methylation. We present an updated Clinical Nanopore Cas9-Targeted Sequencing (Clin-CATS) workflow for analyzing repeat expansions, now compatible with the Oxford Nanopore Technologies R10 flow cell. The workflow incorporates the ONT wf-human-variation Epi2Me workflow, including the Straglr tool to analyze basecalled reads, ensuring compatibility with past, current, and future sequencing chemistries. It expands the number of genes analyzed from 10 to 27 within the ataxia panel and introduces new gene panels for myopathy, neurodegeneration, and ALS/motor neuron disease. Validated with Coriell reference and clinical samples, this method improves the analysis of pathogenic repeat expansions, providing deeper insights into repeat structures while addressing the limitations of traditional approaches.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-19T16:25:34.347448+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001865","title":"Multiregional whole exome sequencing of mesothelioma tumors of MEDUSA cohort","description":"MEDUSA (Mesotheliomaevolution: deciphering druggable somatic alterations) is a translational research platform to build predictive models to stratify existing therapies. This study utilizes multiregional mesothelioma exome sequencing to infer a human evolutionary model of MPM tumorigenesis and understand the inter-relationships that exist between genomic ITH, host immune surveillance and clinical phenotype.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[33741915],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001866","title":"Cold-induced GDF15-secreting adipocyte subpopulation regulates energy homeostasis through endocrine signaling","description":"This study investigates how brown adipose tissue maintains energy homeostasis when UCP1-mediated thermogenesis is impaired. Using single-nucleus RNA sequencing of BAT from cold-exposed Ucp1 knockout mice, we identified a distinct brown adipocyte subpopulation (U2) with enriched expression of the batokine GDF15. Functional analyses demonstrate that GDF15-GFRAL signaling is required to sustain energy expenditure in adipose tissue and regulate food intake as a compensatory mechanism. Additionally, human deep neck adipose tissue RNA-seq data reveals an inverse correlation between UCP1 and GDF15 expression, suggesting an evolutionarily conserved regulatory axis.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001867","title":"PEACE mesothelioma study - whole exome multiregion sequencing data","description":"This study is one branch of PEACE (Posthumous Evaluation of Advanced Cancer Environment) of mesothelioma cohort, in which post-mortem multiregional tissue sampling of primary and metastatic malignant mesothelioma were banked. \r\n\r\n","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001868","title":"MOLECULAR PROFILING UNVEILS ACTINIC KERATOSIS SUBTYPES AND THE TRANSCRIPTOMIC SPECTRUM OF CUTANEOUS SQUAMOUS CELL CARCINOMA PROGRESSION","description":"This study comprises RNA-seq transcriptomic data from human skin samples, including normal skin, actinic keratoses and cutaneous squamous cell carcinoma. The study aims to investigate gene expression changes associated with keratinocyte carcinogenesis and the progression from normal skin to precancerous lesions and invasive cutaneous squamous cell carcinoma.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001869","title":"Loss of astrocytic markers and impaired metabolic function in spinocerebellar ataxia type 7 patient-derived neural cultures","description":"Spinocerebellar ataxia type 7 (SCA7) is a rare neurodegenerative disorder caused by a CAG repeat expansion in the ATXN7 gene. This repeat expansion results in an abnormally long polyglutamine (PolyQ) tract in the Ataxin-7 protein. This ultimately leads to the degeneration of most notably Purkinje cells and retinal cells. Because no treatment exist that can halt or slow disease progression, there is a critical need for patient-specific disease models to uncover new pathogenic mechanisms and enable therapeutic testing. In this study, induced human pluripotent stem cells (hiPSCs) derived from healthy controls and individuals with SCA7 were differentiated into a mixed neural cell population consisting of neurons and astrocytes. Although control and SCA7 neurons appeared morphologically similar, SCA7-derived astrocytes exhibited a pronounced loss of the astrocyte-specific markers GFAP and S100B. Transcriptome analysis revealed substantial alterations in genes related to glial differentiation, cellular metabolism and oxygen handling, protein homeostasis, and neuronal differentiation and neuronal signaling. Mitochondrial stress assays further confirmed a mitochondrial phenotype in SCA7 neural cells. Together, these findings demonstrate that hiPSC-derived neural cells provide a robust platform that can be used for studying disease mechanisms and testing potential therapies for SCA7.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-22T10:29:14.729082+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001870","title":"Targeting vulnerabilities in IDH mutant tumours: The model matters WES study","description":"Introduction: Synthetic lethal interactions with IDH1 and IDH2 (IDH) mutations were identified in non-endogenous IDH mutant (IDHmut) AML and glioma models, but are absent in endogenous IDHmut chondrosarcoma cell lines. The translation into successful clinical applications has remained challenging, implying artificially created models do not fully recapitulate endogenous IDHmut tumour biology. The aim of this study was to elucidate if the model system is indeed an important factor to consider when studying therapeutic vulnerabilities in IDHmut tumours.\r\n\r\nMethods: Vector-based and CRISPR-Cas9 approaches were used to introduce or revert the IDH1 mutation in chondrosarcoma cell lines. These isogenic cell line pairs were used to examine the presence of known therapeutic vulnerabilities and their underlying biological mechanisms.\r\n\r\nResults: Vector-based IDHmut chondrosarcoma models showed the previously reported synthetic lethal interactions, but these treatment sensitivities were absent in the CRISPR-edited models. Interestingly, not all vector-based IDHmut cell lines displayed the same therapeutic vulnerabilities. Differences in treatment response were associated with multiple factors, including IDHmut protein expression and D-2-HG levels, in line with the fact that therapeutic vulnerabilities could be induced in the CRISPR-edited models by enhancing D-2-HG levels.\r\n\r\nConclusion: Our findings demonstrate that synthetic lethal interactions observed in vector-based models are often a consequence of IDHmut protein overexpression and supra-physiological D-2-HG levels. These results highlight that relying on artificially created IDHmut models may lead to the identification of therapeutic vulnerabilities that are not present in IDHmut tumours, potentially explaining the poor translation of preclinical findings to clinical trials. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-22T10:29:17.123819+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001871","title":"Targeting vulnerabilities in IDH mutant tumours: The model matters RNAseq study","description":"Introduction: Synthetic lethal interactions with IDH1 and IDH2 (IDH) mutations were identified in non-endogenous IDH mutant (IDHmut) AML and glioma models, but are absent in endogenous IDHmut chondrosarcoma cell lines. The translation into successful clinical applications has remained challenging, implying artificially created models do not fully recapitulate endogenous IDHmut tumour biology. The aim of this study was to elucidate if the model system is indeed an important factor to consider when studying therapeutic vulnerabilities in IDHmut tumours.\r\n\r\nMethods: Vector-based and CRISPR-Cas9 approaches were used to introduce or revert the IDH1 mutation in chondrosarcoma cell lines. These isogenic cell line pairs were used to examine the presence of known therapeutic vulnerabilities and their underlying biological mechanisms.\r\n\r\nResults: Vector-based IDHmut chondrosarcoma models showed the previously reported synthetic lethal interactions, but these treatment sensitivities were absent in the CRISPR-edited models. Interestingly, not all vector-based IDHmut cell lines displayed the same therapeutic vulnerabilities. Differences in treatment response were associated with multiple factors, including IDHmut protein expression and D-2-HG levels, in line with the fact that therapeutic vulnerabilities could be induced in the CRISPR-edited models by enhancing D-2-HG levels.\r\n\r\nConclusion: Our findings demonstrate that synthetic lethal interactions observed in vector-based models are often a consequence of IDHmut protein overexpression and supra-physiological D-2-HG levels. These results highlight that relying on artificially created IDHmut models may lead to the identification of therapeutic vulnerabilities that are not present in IDHmut tumours, potentially explaining the poor translation of preclinical findings to clinical trials. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-22T10:29:17.123819+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001872","title":"A single-cell multi-omic atlas of the human pancreas reveals latent plasticity across development, health, and disease","description":"The pancreas plays a central role in major human diseases, yet our understanding of its cellular diversity and plasticity remains incomplete. Here, we present a single-cell multiomics atlas of the human pancreas, profiling over four million cells and nuclei from 57 donors across fetal development, adult homeostasis, and type 2 diabetes (T2D). Integrating sc/snRNA-seq, snATAC-seq, VASA-seq, spatial transcriptomics (Xenium), and multiplexed proteomics (CODEX), we resolve gene expression, chromatin accessibility, and spatial organization at high resolution. We identify transcriptionally plastic centroacinar-like cells (pCACs) in adults with fetal-like features, delineate endocrine and exocrine lineage trajectories during development, and uncover HNF1A-defined beta cell epigenetic states. In T2D, we observe shifts in beta cell subtypes and altered regulatory programs. Glucose perturbation of healthy islets reveals cell-type-specific adaptation and stress responses. This atlas provides a foundational framework to understand pancreas biology and the role of cellular plasticity in regeneration and disease.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[42586061],"external_links":null,"is_released":true,"released_date":"2026-09-02T17:07:24.36025+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001873","title":"GERAS - Genome Wide Analysis of Epigenetic Changes in Aging","description":"ChIP-seq of the PBMCs of donors of different ages.\r\n","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001874","title":"GERAS - Genome Wide Analysis of Epigenetic Changes in Aging","description":"ATAC-seq of the PBMCs of donors of different ages","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001875","title":"Single-cell and spatial transcriptomic profiling of peritoneal metastasis of gastric cancer","description":"Peritoneal metastasis is associated with disease progression and poor prognosis in gastric cancer. This study uses single-cell RNA sequencing and spatial transcriptomics to characterize the cellular composition, tumor microenvironment heterogeneity, and potential therapeutic vulnerabilities in peritoneal metastasis of gastric cancer. Human peritoneal metastatic samples and humanized mouse models engrafted with human gastric cancer cells were analyzed to investigate tumor and immune microenvironment features.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-11T16:11:33.752853+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001876","title":"Single-cell transcriptomic profiling of iPSC-derived cerebral organoids from pediatric ADHD patients and healthy controls","description":"This study investigates neurodevelopmental mechanisms associated with Attention-Deficit/Hyperactivity Disorder (ADHD) using single-cell RNA sequencing of human iPSC-derived cerebral organoids from pediatric ADHD patients and matched healthy controls. The dataset includes transcriptomic profiles generated using the 10x Genomics Chromium platform and Illumina NovaSeq sequencing.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-22T10:29:48.036181+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001877","title":"Single-cell RNA sequencing (scRNA-seq) of healthy pleura and epithelioid PM samples","description":"A comprehensive understanding of pleural mesothelioma (PM) and its tumor microenvironment (TME) is foundational for improving patient stratification and treatment strategies. Using single-cell RNA sequencing (scRNA-seq) on 4 normal pleurae and 11 epithelioid PM samples from untreated and post-chemotherapy patients, over 78,000 single-cell profiles exposed tumor and TME heterogeneity, alterations and interactions that enable disease adaptability and resistance to therapy.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001878","title":"A human lung organoid co-culture model of early bone sarcoma metastasis reveals contact-dependent epithelial remodeling at the metastatic interface","description":"This submission contains scRNA-seq data of human lung organoid monocultures and lung organoids co-cultured with osteo- and Ewing-sarcoma cells from primary tumors and metastases, bulk RNA-seq data of lung organoids and spatial transcriptomics data of primary and metastatic osteo- and Ewing-sarcoma. These datasets were used to characterize lung organoids and to dissect the fibrotic response of the lung organoid cells when co-cultured with tumor cells, on the transcriptomic level.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001879","title":"Tumor-derived monocytes migrating into the draining lymph node support medullary CD8+ T cell exhaustion","description":"Tumor-draining lymph nodes (TDLN) are sites for activation and differentiation of anti-tumor T cells. How tumor-induced architectural rearrangements affect T cell function in non-metastatic TDLN is largely unexplored. To dissect cancer-driven lymph node remodeling, we quantified spatial and transcriptional reorganization of TDLN in a mouse model of oral carcinoma. TDLN were dominated by an expanding lymphatic-medullary niche enriched in infiltrating monocytes. These monocytes trafficked from the tumor into the TDLN, where they promoted an inflammatory milieu driving medullary CD8+ T cell exhaustion and proliferation. In oral carcinoma patients, we confirmed monocyte enrichment in TDLN, medullary localization, and association with exhausted T cells; revealing a conserved, tumor-driven medullary monocyte niche that regulates CD8+ T cell function in cancer.\r\nThis study contains 10x Genomics Chromium single-cell RNA-sequencing data from human tumor-draining cervical lymph nodes (n=7 oral squamous cell carcinoma patients) and cervical lymph nodes from healthy donor controls (n=3), used to validate the phenotypes across species. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001880","title":"Distinct Stem Cell Identities Converge into Shared Erythroid Stress in ERCC6L2 Disease and Shwachman-Diamond Syndrome ","description":"ERCC6L2 disease (ED) is a rare bone marrow failure syndrome caused by biallelic germline mutations in ERCC6L2. ED leads to accumulation of somatic TP53 mutations, myelodysplastic syndrome, and acute myeloid leukemia (AML) with erythroid predominance and poor prognosis. To delineate the transcriptomic events underlying delayed erythropoiesis and leukemic progression in ED, we leverage single-cell transcriptomics and single-cell TP53 genotyping of patient bone marrow across ED and Shwachman-Diamond syndrome. The dataset contains raw single-cell gene expression data (scRNA-seq), raw single-cell amplicon data (scAmp-seq), and curated metadata describing sample identity, cell populations, and disease classification. Related processed data will be available at ArrayExpress.","abstract":null,"study_type":"RNASeq","pubmed_ids":[42311431],"external_links":null,"is_released":true,"released_date":"2026-07-03T10:12:33.232383+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001881","title":"Genetic control of naive B cell receptor gene usage in celiac disease","description":"We have characterized the BCR repertoire of naïve B cells in 102 individuals with CeD and 102 control subjects by undertaking gene usage quantitative trait loci analyses based on BCR repertoire sequencing and single nucleotide polymorphism genotyping within the IGH, IGK and IGL loci.","abstract":null,"study_type":"RNASeq","pubmed_ids":[41748905],"external_links":null,"is_released":true,"released_date":"2026-06-08T14:48:37.122577+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001882","title":"Genetic control of naive T cell receptor gene usage in celiac disease","description":"We have characterized the TCR repertoire of naïve CD4+ T cells in 103 individuals with CeD and 103 control subjects by undertaking gene usage quantitative trait loci analyses based on repertoire sequencing and single nucleotide polymorphism genotyping. Variants within the TCR alpha and beta loci and HLA region as well as HLA-DQ allotypes and alleles were tested for association with TCR gene usage.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-08T14:48:37.043002+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001883","title":"Single-cell transcriptomics of HBV-related HCC in sub-Saharan Africa","description":"This project uses portable HIVE single-cell RNA sequencing to characterise HBV-associated hepatocellular carcinoma in sub-Saharan African patients, an underrepresented population in liver cancer genomics. It identifies aggressive malignant transcriptional programs linked to oxidative stress, iron handling, ferroptosis resistance, tumour microenvironment remodelling, and poorer survival, providing a foundation for more context-specific therapeutic strategies in African HCC. \r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001884","title":"TCR repertoire analysis to analyse T cell clones specific to Staphylococcus aureus serine protease-like protein B","description":"Skin biopsies as well as PBMC after cultivation in absence or presence of recombinant Staphylococcus aureus serine protease-like protein B of five patients with atopic dermatitis were analysed by TCR sequencing.\r\n","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-22T12:50:00.438778+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001885","title":"Germline ALK variant in patient with neurodisability and neuroblastoma","description":"Anaplastic Lymphoma Kinase (ALK) is a transmembrane receptor tyrosine kinase involved in nervous system development. Germline ALK mutations are the commonest cause of hereditary neuroblastoma, usually without a neurodevelopmental phenotype. We report a child with congenital low- risk neuroblastoma, developmental delay, feeding difficulties, poor growth and a de novo heterozygous, germline F1174L ALK mutation. The child was treated with the 3rd generation ALK inhibitor lorlatinib from 6 years of age, with marked symptom improvement. To our knowledge this is the first report of both this germline ALK mutation and use of an ALK inhibitor to treat the associated phenotype.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001886","title":"Proteomics of human cancer-associated T cells identifies regulators of T cell functionality","description":"CD8⁺ T cells in solid tumors progressively lose anti-tumor activity, yet the cell-intrinsic mechanisms driving this loss of function remain incompletely defined. Here, we performed matched proteomic and transcriptomic profiling of dysfunctional and bystander CD8⁺ tumor-infiltrating T cells isolated from primary tumors of treatment-naïve non-small cell lung cancer patients. Proteomic analysis revealed widespread discordance with mRNA expression, with 8% of differentially expressed proteins detected exclusively at the protein level. Genetic perturbation of such differentially expressed proteins identified the chromatin remodeler CHD4 and fatty acid synthase (FASN) as cell-intrinsic regulators of T cell function. CHD4 deletion promoted effector differentiation and enhanced cytokine production, whereas FASN deletion preserved mitochondrial fitness and sustained T cell functionality under chronic T cell receptor stimulation. Together, these findings demonstrate that proteomic profiling uncovers regulators of T cell functionality that are not apparent from transcriptomic analyses alone, highlighting an additional layer of regulatory control.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-26T15:00:40.0716+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001887","title":"LRSomatic: Long-read and short-read somatic sequencing of clear cell sarcoma case CCS15","description":"Whole-genome sequencing of a clinical clear cell sarcoma case (CCS15), comprising a metastatic tumour and matched normal muscle tissue. The tumour and normal were profiled by PacBio HiFi and Oxford Nanopore Fiber-seq (long-read) and by Illumina short-read WGS. Data were generated to benchmark the LRSomatic long-read somatic variant-calling pipeline.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001888","title":"Identification of broadly tumor-reactive γδ TCRs from multiple myeloma","description":"We used single-cell CITE + TCR sequencing to identify tumor-reactive gamma delta TCR sequences from multiple myeloma patient bone marrow samples. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-27T10:18:17.500696+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001889","title":"Investigating adaptive immune responses in MM patients treated with belantamab mafodotin","description":"We used single-cell CITE + VDJ sequencing and CapTCRseq to investigate the adaptive immune response, specifically the role of T cells and tumor-reactive gamma delta T cells, in multiple myeloma patients treated with belantamab mafodotin from the on-going Algonquin clinical trial (NCT03715478).","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-27T10:18:11.804551+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001890","title":"DNA Methylation in CCR8+ Treg cells from tumors and normal adjacent tissues","description":"We compared the DNA methylation in CCR8+ Treg cells from human tumors (kidney and liver) and normal adjacent tissues, using whole-genome bisulfite sequencing","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001891","title":"Gene expression in CCR8+ Treg cells from tumors and normal adjacent tissues","description":"We compared gene expression in CCR8+ Treg cells from human tumors (kidney and liver) and normal adjacent tissues, using bulk RNA sequencing","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001892","title":"Single-cell chromatin accessibility in T cells from tumors and normal adjacent tissues","description":"We compared the chromatin accessibility in T cells from human tumors (kidney and liver) and normal adjacent tissues, using single-cell ATAC-seq. Focus: CCR8+ Treg cells","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001893","title":"Single-cell gene expression and T cell receptor repertoire in immune cells from tumors, normal adjacent tissues and blood","description":"We compared single-cell-level gene expression in immune cells from human kidney tumors, normal adjacent tissues, and blood, together with the T cell receptor repertoire. Focus: CCR8+ Treg cells. We utilized multimodal single-cell RNA-TCR sequencing.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001894","title":"Screening for Prostate Cancer-Specific Differentially Methylated Regions Based on  MeDIP-seq ","description":"Methylated DNA Immunoprecipitation Sequencing (MeDIP-seq) on tissue samples from prostate cancer, benign prostatic hyperplasia (BPH), and bladder cancer.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-22T12:50:24.189661+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001895","title":"Screening for Prostate Cancer-Specific Differentially Methylated Regions Based on  BSAC","description":"Bisulfite Amplicon Sequencing on tissue samples from prostate cancer, benign prostatic hyperplasia (BPH), and bladder cancer.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-22T12:50:24.189661+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001896","title":"Single cell analysis reveals molecular traits of pediatric lymphoma resistant subclones","description":"How relapse/refractory derive from pediatric lymphoma is unclear. We prepared scRNA-seq and scVDJ-seq data from fresh pediatric lymphoma samples. Samples include Burkitt Lymphoma (pBL; n=3), T cell lymphoblastic lymphoma (pTLBL; n=5) as well as 8 non-cancerous reactive lymph nodes from children (pReLy). We integrated non cancerous pReLy to each cancer types to reveal unique trait of lymphoma. The provided data includes Seurat CCA integration of pReLy to each type of the lymphomas ready to import into R environment as .RDS file. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001897","title":"Single-cell RNA and TCR sequencing of CSF cells and PBMCs from individuals with neurological disorders","description":"We performed single-cell RNA sequencing combined with T-cell receptor sequencing to characterize immune cells from cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) of patients with multiple sclerosis and individuals with other inflammatory neurological diseases used as controls. The aim of this study was to identify and characterize T cells with TCRs shared among people with MS and enriched in the CSF compartment.\r\n","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-10T13:59:42.712944+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001898","title":"Biological determinants of prostate cancer response to neoadjuvant hormone therapy","description":"We performed transcriptome-wide profiling (RNA) of pre- and post-treatment cancers from fresh-frozen tissue obtained from prostatectomy of patients with high-risk prostate cancer. Post treatment samples (n=40) were obtained from a Phase 2 randomised clinical trial called ARNEO (NCT03080116) where patients received degarelix with placebo or degarelix with apalutamide for 12 weeks. Risk-matched, treatment-naive cohort were used as controls (n=20). The aim of this project was to carry out molecular characterization that capture the different effects of neoadjuvant hormone therapy.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001899","title":"IMMUcan NSCLC cohort","description":"The goal of IMMUcan is to understand how the immune system interacts with tumors and how therapeutic interventions influence this interaction. This cohort includes patient with confirmed metastatic NSCLC, naïve of treatment in the metastatic settings, to be treated in 1st line. Comprehensive profiling data are integrated with longitudinally collected clinical information. Cellular profiling of the same tumor samples was performed using multiplex immunofluorescence imaging, imaging mass cytometry, and H&E staining.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001900","title":"From stem cells to somites: revealing genetic and exogenous factors of human embryogenesis","description":" Stem cell-based human embryo models offer an ethically tractable platform for studying early human development. This study employs somitoids, three-dimensional models of human somitogenesis, to investigate how transcriptional programs and culture conditions influence somite formation and segmentation. Pre-differentiation conditions strongly impact developmental potential, with StemFit medium outperforming mTeSR Plus in generating robust somite-like structures, despite minimal differences in transcriptomic and proteomic profiles.\r\nRNA-seq was performed on iPSCs cultured in mTeSR Plus or StemFit medium, as well as on day 5 somitoids derived from these conditions. Additional RNA-seq analyses included wildtype, BPTF, RBPJ, and CITED2 knockout lines, and CITED2 rescue lines. These targets were selected based on p300 proximity labeling to functionally validate identified p300 proximity interactors. To confirm that the p300–miniTurbo fusion remained functional, ChIP-seq was performed on undifferentiated iPSCs cultured in mTeSR Plus medium. \r\nTogether, our findings highlight somitoids as a robust and scalable system for studying gene regulation during early human development, enabling functional interrogation of key chromatin-associated regulators driving somitogenesis.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001901","title":"Circulating mRNA and miRNA signatures predicting response to lifestyle intervention in pediatric obesity","description":"This study aims to identify circulating transcriptomic biomarkers predictive of response to lifestyle intervention in pediatric obesity. Peripheral blood whole-transcriptome RNA sequencing and microRNA sequencing were performed in a subset of children and adolescents with obesity participating in a prospective 12-month multicenter lifestyle modification program. The generated data are linked to detailed demographic, clinical, anthropometric, biochemical, and treatment outcome variables. These resources support investigations of molecular pathways underlying obesity, treatment responsiveness, and precision medicine approaches in pediatric obesity management.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-11T16:57:05.760722+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001902","title":"ATACseq of CD4 and CD8 T cells from CLL patients and age-matched HD","description":"This study investigates chromatin accessibility landscapes in CD4+ and CD8+ T cells from patients with chronic lymphocytic leukemia (CLL) and age-matched healthy donors (HD).  Briefly, peripheral blood T cells were isolated using magnetic bead-based negative selection, with CD4+ or CD8+ fractions further purified by FACS sorting. Samples were either used at baseline or after 2 days of acd3-cd28 stimulation in vitro.  ATAC-seq libraries were generated using the Omni-ATAC protocol and sequenced as paired-end reads on an Illumina NovaSeq platform. Data were processed using the ENCODE ATAC-seq pipeline, including quality control, adapter trimming, alignment to the GRCh38 reference genome, duplicate removal, and assessment of library quality metrics. Accessible chromatin regions were identified by peak calling, followed by differential accessibility analysis between CLL and HD samples using DESeq2 within DiffBind. The study aims to define disease-associated regulatory changes in T cell subsets in CLL, with emphasis on epigenetic alterations underlying T cell dysfunction we report in out in vitro readouts.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-19T09:40:17.485954+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001903","title":"Integrative spatial transcriptomics and single-cell proteomics of esophageal adenocarcinomas define a macrophage- and CAF-enriched tumor surrounding shield","description":"Esophageal adenocarcinoma (EAC) is characterized by a complex tumor microenvironment that influences disease progression and therapeutic response. This study aimed to investigate the spatial organization and cellular composition of EAC using integrative spatial transcriptomics and single-cell proteomic analyses. By profiling tumor and surrounding tissues from multiple patients, we sought to identify cellular interactions and microenvironmental features associated with tumor biology. The study provides insights into macrophage- and cancer-associated fibroblast-rich niches that may contribute to tumor protection and progression.\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001904","title":"Ultra-sensitive ctDNA monitoring required for predicting response and resistance to immunotherapy in melanoma","description":"Treatment with immune checkpoint inhibitors (ICIs) has markedly improved outcomes in melanoma but remains limited by toxicity and treatment failure in ~50% of patients. Conventional clinicopathological factors lack sufficient precision to identify patients at highest risk, leading to both under- and overtreatment. Circulating tumor DNA (ctDNA) has emerged as a highly specific biomarker for molecular residual disease (MRD) detection and offers the potential to enable real-time, minimally invasive monitoring to guide personalized ICI strategies.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001905","title":"Tumor and peripheral biomarker analysis from the phase 3 CheckMate 9ER trial of nivolumab plus cabozantinib versus sunitinib for advanced renal cell carcinoma","description":"Integrative tumor immunohistochemical, genomic, and transcriptomic analyses found T cell density, SETD2 mutational status, high inflammatory response and oxidative stress to be  associated with NIVO+CABO outcomes versus sunitinib. EMT and CAF pathways were associated with resistance to NIVO+CABO. Further, clinical outcomes were improved with NIVO+CABO versus sunitinib across 6 transcriptomically-defined clusters; T-effector/proliferative cluster was enriched for c-MET positivity which differentiated NIVO+CABO outcomes. Among circulating factors, high IL-6, TN-C, and TIMP-1 were predictive of NIVO+CABO outcomes versus SUN. NIVO+CABO increased levels of cytokines associated with immune activation/inflammation/oxidative stress These results support metabolic/immune pathway activation within the tumor and peripheral circulation as possible contributors to PD-1 based efficacy.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001906","title":"scRNA-seq of CD45+ lymphocytes from 22q11.2del patients","description":"Patients with inborn error of immunity (IEI), particularly those affecting T-cell development, provide a unique opportunity to analyse the shape of the human cILC compartment. \r\nFrozen samples of four 22q11.2del patients (P20-P23, table 1) were stained with anti-human CD45-APC/Cy7 antibody after thawing and each patient sample was sorted on CD45+ lymphocytes. Freshly sorted CD45+ lymphocytes of each patient were multiplexed per donor and multiple tags were used per donor, depending on cell counts. In total, 10 different oligo-coupled sample tag antibodies were used. To increase the yield, patients with higher cell counts were tagged with multiple tags (3x tags P20 and P22, 2x tags for P21, and 1x tag for P23) and combined with Abseq staining. Next, scRNA-seq was performed from four 22q11.2del patients using the BD Rhapsody pipeline. Total cILC counts were reduced, primarily driven by a marked reduction of cILC1s. scRNAseq analyses showed that cILC1s shared T-cell-associated gene programs.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001907","title":"Plasma cell-free small RNA sequencing comparison of Illumina and Ultima Genomics in pancreatic cancer","description":"This study evaluates plasma-derived cell-free small RNA sequencing in a case-control cohort of 39 pancreatic ductal adenocarcinoma patients and 39 control subjects. Cell-free nucleic acids were isolated from plasma, small RNA libraries were prepared using the SMARTer smRNA-Seq workflow, and the same libraries were sequenced on both Illumina NovaSeq 6000 and Ultima Genomics UG 100 platforms. The project aims to compare platform performance for circulating small RNA and mature microRNA profiling, including read yield, alignment, RNA biotype composition, mature miRNA detection, expression concordance, and pancreatic cancer-associated differential expression. The dataset supports benchmarking of cross-platform reproducibility and assessment of biologically relevant plasma microRNA signals in pancreatic cancer.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-30T08:28:11.204822+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001908","title":"Frequency and prognostic significance of genetic abnormalities in a subgroup of intermediate risk neuroblastoma patients: A SIOPEN study","description":"Intermediate risk neuroblastoma includes a rare subgroup of patients over the age of 18 months at diagnosis with unresectable, localised tumours with unfavourable histology without MYCN amplification. This group is treated differently around the world with some patients receiving upfront myeloablative therapy (MAT) in addition to standard treatment with chemotherapy, surgery, radiotherapy and 13 cis retinoic acid, but the overall 5-year patient survival with or without MAT is similar (75%). This study aimed to understand the neuroblastoma biology of this rare patient subgroup. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-29T09:57:24.922666+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001909","title":"GERAS - Genome Wide Analysis of Epigenetic Changes in Aging (scMultiomics)","description":"Aging is associated with epigenetic modifications. In this study, we performed Single-cell multi-omics analyses on PBMCs from male and female donors of different ages. Based on this, we investigate chromatin accessibility and gene expression changes at the single-cell level.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001910","title":"High-grade serous ovarian cancer is associated with increased TP53 mutation burden in uterine lavage","description":"High grade serous ovarian cancer (HGSC) has low survival partly due to the lack of methods for detection, diagnosis, and risk prediction. TP53 mutations, which drive HGSC, are found in gynecological tissues as the result of somatic evolution, but it is unknown whether an excess of mutations is linked to ovarian cancer. Here we investigate if TP53 mutation burden measured in uterine lavage, a minimally invasive gynecological liquid biopsy, can discriminate between patients with and without HGSC. We used ultradeep TP53 duplex sequencing (>15,000x duplex depth) to detect TP53 mutations in uterine lavage collected pre-operatively in 278 patients undergoing gynecological surgery for pelvic masses (average risk) or cancer risk-reduction (high risk). All lavages contained multiple TP53 mutant clones, which were used to quantify TP53 mutation burden frequency (MBF). Average risk patients with HGSC had significantly higher TP53 MBF independently of age and other risk factors (77% sensitivity, 89% specificity, AUC =0.88). Excluding tumor TP53 clonal mutations from the lavage MBF calculation maintains this association, suggesting that it is the overall TP53 somatic mutation burden (rather than the discovery of the specific tumor driver mutation) that identifies HGSC. These results demonstrate that TP53 somatic mutations are common in uterine lavage but more abundant in patients with HGSC, highlighting a connection between TP53 somatic evolution and ovarian cancer. Uterine lavage offers a minimally invasive approach that could be valuable to identify patients with HGSC.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-08T09:28:39.928843+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001911","title":"NF2 deficient IPSC-derived spheroids","description":"NF2 -related Schwannomatosis ( NF2 -SWN) is an inherited autosomal dominant disorder resulting from loss-of-function mutations in the NF2 gene, for which no effective treatment is currently available. Furthermore, truncating variants in NF2 are associated with the severest phenotype compared to in-frame or missense variants. Previously, a shorter NF2 isoform with exon 11 skipped (merlin_e-11), induced through antisense morpholino oligomers (PMOs), was able to partially rescue the deleterious effect of nonsense variants located at that exon in patients’ primary fibroblast. To test the potential of this approach into Schwann cells, those responsible of NF2 -SWN tumours, we developed an iPSC-based model carrying heterozygous and homozygous truncating variants on exon 11 of the NF2 gene and differentiated them to Schwann cells forming spheroids. Once the model was already stablished, we have treated this spheroids with the PMO treatment. The RNA-Seq that we present in this study is the result of treating this spheroid model with the PMO treatment at different timepoints.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-30T15:19:45.499842+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001912","title":"Transcriptional profiling and clonality analysis of small intestinal and bone marrow plasma cells","description":"This study contains single-cell RNA sequencing data (gene expression, VDJ and feature barcodes) for paired samples of small intestinal plasma cells and bone marrow plasma cells isolated from four patients with celiac disease.\r\n\r\nThe mucosa lining the gastrointestinal tract harbors the body’s largest population of plasma cells, most of which produce dimeric IgA destined for release into the lumen. In addition, there is systemic production of monomeric IgA circulating in the blood. Little is known about the connection between systemic and mucosal IgA. To address this relationship and to explore antibody responses against the microbiota, we isolated bacteria from duodenal biopsies and assessed antibody reactivity. Systemic IgA showed reactivity to bacteria of the upper gastrointestinal tract with a preference for binding Neisseria species, while duodenal IgA showed broader reactivity. Single-cell RNA sequencing of gut and bone marrow plasma cells demonstrated limited clonal overlap between the two compartments. Yet, a few shared clones specific to bacterial antigens were identified. Overall, gut and bone marrow plasma cells have distinct V(D)J repertoires and IgA subclass distributions, and they likely depend on B-cell activation at discrete anatomical sites.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-06-23T09:17:01.257937+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001913","title":"Single-cell DNA sequencing reveals a high incidence of chromosomal abnormalities in human blastocysts","description":"Single cell DNA sequencing data from human preimplantation stage embryos from embryonic day 5 to 8, donated for research","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[38175717],"external_links":null,"is_released":true,"released_date":"2026-07-02T13:24:58.345512+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001914","title":"Transcriptome profiling of liver metastasis-derived colorectal cancer organoids to dissect pro-differentiative effects of TGFB1 and IL-6","description":"Bulk RNA sequencing was performed on patient-derived xenograft (PDX)-derived organoid models of metastatic colorectal cancer (mCRC). The aim of this study was to test the effect of IL-6 and TGFbeta1 on mCRC organoid cell differentiation. Transcriptomic profiling was conducted following cytokine treatments to investigate molecular changes associated with treatments. Three biological replicates were included for each experimental condition (control, IL-6, and TGF-beta1 treatments).","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-09T16:51:19.455363+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001915","title":"Single-cell RNA-Seq","description":"Single-cell gene expression and TCR sequencing of unstimulated PBLs, neoantigen-stimulated PBLs, and neoantigen-stimulated TILs.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-26T17:04:50.735414+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001916","title":"Plasma Nucleosome Profiling Reports on Tumor Burden and Molecular Subtypes in Small Cell Lung Cancer","description":"Small cell lung cancer (SCLC) is an aggressive malignancy with dismal prognosis and marked transcriptional heterogeneity that drives distinct therapeutic vulnerabilities. The clinical translation of these molecular insights is limited by limited access to tumor biopsies. Here, we apply chromatin immunoprecipitation of cell-free nucleosomes carrying active histone modifications followed by sequencing (cfChIP-seq) to 441 plasma samples from individuals with advanced SCLC, other neuroendocrine carcinomas (NEC), non-SCLC cancers, and healthy controls. cfChIP-seq faithfully captured the epigenetic and transcriptional landscape of tumor-derived cfDNA, including SCLC tissue/cell-of-origin signatures, and yielded a quantitative score of tumor fraction that tracked radiographic burden and prognosis. Integrating plasma cfChIP-seq with matched tumor transcriptomes (n = 73, including 41 time-matched pairs), we show that cfChIP-seq levels at promoters of lineage-defining transcription factors (ASCL1, NEUROD1, POU2F3, and ATOH1) correlate strongly with tumor RNA and support noninvasive inference of SCLC transcriptional subtypes directly from plasma. These findings establish cfChIP-seq as a practical liquid-biopsy platform that reports real-time tumor state and subtype, enabling precision monitoring and laying the groundwork for subtype-informed therapeutic stratification in SCLC.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-14T16:35:03.212955+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001917","title":"Single-cell RNA sequencing of human infant gut","description":"This submission contains metadata for the study \"Single-cell RNA sequencing of the human infant gut\". The dataset comprises single-cell RNA sequencing data generated from sorted γδ T cells isolated from infant gut samples. Two samples, one from the colon and one from the small intestine, were sequenced using an Illumina platform with the aim to characterize gene expression profiles of γδ T cells during early human development.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-03T10:27:05.746377+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001918","title":"Co culture scRNAseq PARSE","description":"Fastq files are divided into 2 groups (WT and Mini). For alignment please use their respective loading table to run splitpipe from PARSE","abstract":null,"study_type":"RNASeq","pubmed_ids":[41912267],"external_links":null,"is_released":true,"released_date":"2026-07-03T10:28:08.410326+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001919","title":"Clonal T cell expansion defines divergent lymphoid-rich spatial microenvironments in renal cell carcinoma","description":"We identify distinct tumour-immune microenvironments in renal cell carcinoma using an integrated multi-modal approach combining single-cell RNA/TCR/BCR sequencing, bulk transcriptomics and spatial profiling technologies. By integrating these complementary datasets, we characterize unique cellular interactions, receptor-ligand signaling networks, and localized pathway activation patterns across tumour microenvironments.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001920","title":"Lynch syndrome adenoma and carcinoma samples","description":"The dataset consists of high-coverage, PCR-free Whole Genome Sequencing (WGS) data (up to 100x coverage, processed via the DRAGEN pipeline) from human tissue samples. The objective is to analyze recurrent mutations and early-stage clonal evolution to identify preventative vaccine targets.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001921","title":"Whole-exome sequencing of EBV-positive diffuse large B-cell lymphoma","description":"This dataset contains whole-exome sequencing data from 34 EBV-positive diffuse large B-cell lymphoma (EBV+ DLBCL) cases collected at the University of Lübeck. Sequencing was performed to characterize the mutational landscape of EBV+ DLBCL, including somatic single nucleotide variants, insertions/deletions, and copy number alterations. Data were processed using the nf-core/sarek pipeline with GRCh38 as the reference genome. These data support the study \"PD-L1-linked spatial architecture of immune evasion in EBV-positive diffuse large B-cell lymphoma.\"","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001922","title":"Visium FFPE spatial transcriptomics of EBV-positive diffuse large B-cell lymphoma","description":"This dataset contains Visium FFPE spatial transcriptomics data from 18 EBV-positive diffuse large B-cell lymphoma cases collected at the University of Lübeck, Germany. Spatial gene expression libraries were generated using the 10x Genomics Visium for FFPE Gene Expression platform and sequenced on an Illumina NovaSeq 6000. Raw FASTQ files were processed using Space Ranger v3.1.0 with the human reference genome GRCh38. These data were used to characterize the spatial tumor immune microenvironment in relation to PD-L1 copy number status and support the study \"PD-L1-linked spatial architecture of immune evasion in EBV-positive diffuse large B-cell lymphoma.\"","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001923","title":"Bulk RNA sequencing of EBV-positive diffuse large B-cell lymphoma","description":"This dataset contains bulk RNA sequencing data from 32 EBV-positive diffuse large B-cell lymphoma (EBV+ DLBCL) cases collected at the University of Lübeck. Sequencing was performed to characterize transcriptional differences between tumors with and without PD-L1 copy number gains, including differential gene expression, gene set enrichment, and immune cell deconvolution analyses. Data were processed using the nf-core/rnaseq pipeline with GRCh38 as the reference genome. These data support the study \"PD-L1-linked spatial architecture of immune evasion in EBV-positive diffuse large B-cell lymphoma.\"","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001924","title":"Single-cell RNA sequencing of EBV-positive diffuse large B-cell lymphoma","description":"This dataset contains single-cell RNA sequencing data from 10 EBV-positive diffuse large B-cell lymphoma cases collected at the University of Lübeck, Germany. Cells were profiled using the 10x Genomics Chromium platform on FFPE tumor tissue. Samples were multiplexed into three pools and sequenced on an Illumina NovaSeq 6000 with paired-end reads. Raw FASTQ files represent pool-level data prior to genetic demultiplexing. These data support the study \"PD-L1-linked spatial architecture of immune evasion in EBV-positive diffuse large B-cell lymphoma.\"","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001925","title":"A bi-modal small molecule inhibitor of oncogenic miR-10b suppresses tumor metastases","description":"This study investigated the effects of long-term RNA structure–targeted inhibition of miR-10b in the peritoneal carcinomatosis–derived gastric adenocarcinoma patient-derived xenograft (PDX) cell line, GA0518. GA0518 cells were chronically exposed to a small-molecule miR-10b inhibitor (1 µM) for 48 hours, 2 months (P18), and 4 months (P30) to evaluate both acute and sustained molecular responses. miR-10b expression profiles were assessed at each time point using RT-qPCR and whole-exome sequencing. Whole-exome sequencing further identified the emergence and persistence of a dominant cellular clone associated with prolonged miR-10b inhibition.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001926","title":"Efficacy of Cabozantinib Plus Nivolumab in Cluster 1/2 Metastatic Clear Cell Renal Cell Carcinoma: Results from OPTIC RCC, a Phase II Trial of a Novel RNA-seq-based Biomarker","description":"Background. First-line treatment of metastatic clear cell renal cell carcinoma (ccRCC) includes a PD-1 inhibitor plus either an anti-CTLA-4 antibody (IO/IO) or a vascular endothelial growth factor receptor tyrosine kinase inhibitor (IO/TKI). IO/TKI treatment applied to patients with angiogenic-driven tumors may lead to improved clinical outcomes. Methods. OPTIC RCC (NCT 05361720) is a prospective phase II multicenter clinical trial that assigns front-line metastatic ccRCC patients to either nivolumab/cabozantinib (cluster 1/2; Cluster Angio) or ipilimumab/nivolumab (cluster 4/5; Cluster IO) using a machine learning model developed from the IMmotion 151 RNA-seq-based cluster definitions and run on the Tempus xR whole transcriptome assay. Patients assigned to Cluster Angio are reported here. The primary endpoint is overall response rate (ORR) per RECIST 1.1. Results. 28 patients with Cluster Angio tumors met eligibility criteria and were treated with cabozantinib plus nivolumab. 21 of 28 patients demonstrated an objective response (75%; 95% CI, 55.1–89.3), thus meeting the prespecified primary endpoint of a 75% ORR. All patients achieved a reduction in tumor burden, and no patient experienced progressive disease as best response. The progression free survival (PFS) at 12 months is 68.1% (95% CI, 46.1–82.6%) and median PFS is not reached. 2 of 28 patients achieved >80% tumor reduction at 6 months. Safety and tolerability were typical for nivolumab/cabozantinib given to patients with metastatic ccRCC. Conclusions. To our knowledge, OPTIC RCC is the first ccRCC clinical trial to prospectively use a predictive RNA-seq-based biomarker to guide therapy and achieve its primary endpoint. Using routine RNA-seq to identify angiogenic tumors enriches for clinical benefit to cabozantinib plus nivolumab. (NCT05361720, https://clinicaltrials.gov/study/NCT05361720) ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001927","title":"Single-cell RNA sequencing of liver metastasis-derived colorectal cancer organoids profiling cellular heterogeneity and lineage dynamics across time","description":"The objective of this analysis was to identify, at single-cell resolution, trasncriptionally distinct subpopulations in untreated metastatic colorectal cancer organoids with diverse genetic backgrounds and to investigate their temporal dynamics.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-09T16:51:21.612755+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001928","title":"Population histories of the Indigenous Adivasi and Sinhalese from Sri Lanka using whole genomes","description":"Sri Lanka has played a key role in the peopling of South Asia, with archaeological evidence for human presence on the island dating back to ⁓40,000 years ago. Present-day Indigenous peoples of the island, the Adivasi, are proposed to have descended from early inhabitants of the region, while urban populations like the Sinhalese, the major ethnic group on the island, migrated from India in historical times. Using whole genomes from 19 Adivasi individuals belonging to two clans and from 35 Sinhalese, we find that the Adivasi and Sinhalese share high genetic similarities with each other and with other Sri Lankan and Indian populations, especially those with greater genetic affinity to Ancestral South Indians (ASI). Admixture modeling of the Sri Lankan groups reveals that despite shared ancestral components, the Adivasi retain higher genetic contributions from ancient hunter-gatherers compared with the Sinhalese. Additionally, in contrast to the Sinhalese, the Adivasi have maintained low effective population size and undergone strong founder events, which is consistent with their hunter-gatherer lifestyle, historic relocations, and habitat fragmentation. While the two Adivasi clans are genetically more similar to each other than to any other populations, we observe differing demographic histories, with the Interior Adivasi experiencing a stronger bottleneck than the Coastal Adivasi since their split. This whole-genome-based study addresses gaps in our understanding of the demographic and migratory history of two key Sri Lankan groups and, consequently, of broader South Asia by illuminating complex population structure that has been shaped by both demographic and socio-cultural factors.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-10T10:30:36.662573+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001929","title":"Epigenetic and Transcriptomic profiling of hiPSC- and UCB-HSC derived CD4+CD8+ T progenitors","description":"Generation of T cell subsets from human induced pluripotent stem cells (hiPSCs) in defined in vitro systems could provide a valuable model to study the mechanisms of human T cell development in the thymus and serve as a scalable source for therapeutic cell products. We generated a unique DNA methylation (DNAmeth) and RNA-seq dataset of in vitro generated hiPSC-derived and umbilical cord blood (UCB-) derived T cell progenitor subsets from a feeder-free differentiaion system and integrated them with data from primary human thymocyte populations.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-20T12:22:31.340805+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001930","title":"Zanidatamab in Patients with Early Stage HER2-positive Breast Cancer: The NeoZanHER Phase 2 Single-Arm Open-Label Trial ","description":"Strategies are needed to avoid chemotherapy in early stage HER2-positive (HER2+) breast cancer (BC). We conducted a neoadjuvant therapy trial with zanidatamab, a dual HER2-directed bispecific antibody, in patients with 1-3 cm, node-negative HER2+ BC. Primary endpoint was pathologic complete response (pCR). Secondary endpoints were radiographic response by ultrasound and magnetic resonance imaging. US and MRI, pathologic response by residual cancer burden (RCB), rate of adverse events, feasibility of accrual and biomarkers of response. Fifteen patients with HER2 IHC 3+, and 5 with HER2 IHC 2+/ISH+ BC were enrolled. Patients received zanidatamab 20 mg/kg every 2 weeks for 6 (n=11) or 10 doses (n=9). Fourteen patients also received endocrine therapy. At 6 weeks, there was a significant decrease in tumor size and volume. At surgery, six patients (30%) had pCR, meeting the prespecified pCR target, and four had limited RCB (RCB-1; 20%). Treatment was well tolerated. All patients with pCR had HER2 IHC 3+ tumors, ERBB2 amplification on WES, PAM50 HER2-high subtype, and a trend towards higher HER2 mRNA expression (p=0.06). In conclusion, de-escalation to HER2-targeted therapy alone may be feasible. Further research is needed to refine patient selection. ","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-07T13:30:16.892253+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001931","title":"Molecular profiles comparison of human male and female mammary glands","description":"This study characterizes the molecular features of human male mammary tissue and compares them with pre- and post-menopausal female mammary glands. Using cell sorting, transcriptomic profiling, and histone modification ChIPseq analyses, we identified shared fundamental regulatory networks between sexes but reduced immune activity in male and post-menopausal tissues. In addition, KRASG12D-transduced male luminal progenitors formed ER-positive invasive ductal carcinomas whose gene expression profiles were also compared with normal male luminal progenitors.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001932","title":"Synthetic longitudinal breast cancer  whole-genome sequencing dataset","description":"This study contains fully simulated longitudinal whole-genome sequencing data for one synthetic female breast cancer patient. It includes one matched-normal paired-end sample generated at a nominal depth of 30x and three longitudinal tumour samples generated at a nominal depth of 60x. ","abstract":null,"study_type":"Synthetic Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-24T16:48:35.294237+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001933","title":"Integrated molecular and functional analysis of human primary islets reveals genetic mediators of glycemic regulation and type 2 diabetes","description":"Understanding how genetic variation influences human islet function remains a central challenge in diabetes biology. Here, we establish a donor-matched framework integrating genome-wide genotyping with deep molecular and functional phenotyping of human primary islets across chromatin accessibility, gene expression, protein abundance, and insulin secretion dynamics. A Bayesian hierarchical model standardizes glucose–insulin secretion relationships across heterogeneous assay conditions, enabling direct comparison of donor-specific function. This resource defines the natural physiological variation in human islet function and shows that polygenic risk for type 2 diabetes stratifies insulin secretion and viability with effects comparable to key physiological determinants. Integration of caQTL, eQTL, and pQTL analyses links genetic variation to regulatory mechanisms across molecular layers, while cross-layer colocalization resolves diabetes-associated loci into pathways underlying islet dysfunction. Association testing of in vitro cellular phenotypes enables “GWAS-in-a-dish” to nominate candidate regulators of human islet physiology and therapeutic targets. This framework provides a mechanistic map of human islet variation and a resource for interpreting diabetes risk and prioritizing targets for intervention.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001934","title":"Barcoded ultra-long sequening in haematological malignancies","description":"Barcoded ultra-long read sequencing data from haematological malignancy samples. The samples were cell lines and patient-derived xenografts with leukaemia or lymphoma. The samples were processed using a barcoded ultra-long read sequencing protocol developed for Oxford Nanopore Technology platforms - N50s and coverage are in the associated manuscript. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001935","title":"Investigating the Transcriptomic Profiles and Variation across B-cell Populations in Individuals with Systemic Lupus Erythematosus and Healthy Individuals","description":"This study aimed to characterize transcriptomic profiles of distinct circulating B cell subsets in individuals with systemic lupus erythematosus (SLE) as well as healthy individuals. Single-nuclei RNA-sequencing (snRNA-seq) was performed on CD19+IgD+ cells (naïve B cells), CD19+IgD- cells (memory and double-negative B cells), and CD19- cells isolated using fluorescence-activated cell sorting (FACS) from 3 SLE patients and 2 healthy individuals.\r\n","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001936","title":"Transcriptomic profiling of ALK1 dosage in hiPSC-derived endothelial cells","description":"Bulk RNA sequencing was performed on control and ALK1 KO/KO human induced pluripotent stem cell–derived endothelial cells under unstimulated and BMP-9-stimulated conditions to assess ALK1-dependent transcriptional responses. To investigate dose-dependent transcriptional rescue, bulk RNA-seq was also performed on ALK1 KO/KO endothelial cells following doxycycline-induced re-expression of wild-type ACVRL1. The study aimed to define how ALK1 loss disrupts BMP-9-responsive gene programs and whether low-level ALK1 re-expression is sufficient to restore endothelial transcriptional homeostasis. Bulk RNA-seq data were generated from three independent hiPSC-EC differentiation batches with one to two technical replicates per batch.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001937","title":"Plasma CTCF ChIP-seq Reveals Cancer-Associated cfDNA Binding Profiles","description":"Cell-free DNA (cfDNA) in plasma predominantly exists as nucleoprotein complexes. Although circulating CTCF-bound cfDNA (cfCTCF-DNA) has previously been reported, the occupancy of individual CTCF binding sites in plasma has not been systematically characterised.\r\nThis study describes the isolation of endogenous plasma cfCTCF-DNA by chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) in samples obtained from cancer patients and healthy individuals. A two-step enrichment strategy was employed, combining physical removal of background cfDNA by immunoprecipitation with bioinformatic filtering to remove residual non-CTCF-derived sequences. Sequencing reads were aligned to the UCSC hg38 reference genome using BWA-MEM v0.7.17 and processed to generate CRAM files containing alignments restricted to the primary chromosomes (chr1–chr22, chrX, chrY and chrM).\r\nCTCF-associated cfDNA fragments were classified according to their similarity to a consensus CTCF binding motif, enabling discrimination between low-affinity and high-affinity CTCF binding sites. Comparative analyses identified quantitative and qualitative differences in plasma cfCTCF-DNA profiles between healthy individuals and patients with cancer.\r\nThe deposited dataset comprises plasma cfCTCF-DNA ChIP-seq data from four clinical cohorts and includes both CTCF-enriched and total cfDNA samples where applicable. These data support the investigation of CTCF occupancy patterns as a novel class of liquid biopsy biomarkers for cancer detection and monitoring.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-16T10:57:43.137615+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001938","title":"IMMUcan BC2 cohort","description":"The goal of IMMUcan is to understand how the immune system interacts with tumors and how therapeutic interventions influence this interaction. This cohort includes patients with confirmed localized TNBC (stages I to III) treated with neo-adjuvant therapy Comprehensive profiling data are integrated with longitudinally collected clinical information. Cellular profiling of the same tumor samples was performed using multiplex immunofluorescence imaging, imaging mass cytometry, and H&E staining.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-10T10:18:13.438598+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001939","title":"Whole-Exome Sequencing of Brazilian Non-Small Cell lung Cancer","description":"Lung cancer is a heterogeneous disease with diverse molecular alterations. This study generated whole-exome sequencing (WES) data from Brazilian patients with lung cancer to characterize their genomic landscape and investigate associations between molecular alterations and clinicopathological features. These data provide a valuable resource for studying lung cancer genomics in an admixed Brazilian population.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001940","title":"CSF PBAT methylome profiling in multiple sclerosis - shallow seq","description":"This study contains shallow-depth post-bisulfite adaptor tagging (PBAT) whole-genome bisulfite sequencing data generated from cerebrospinal fluid (CSF) cells from individuals with relapsing-remitting multiple sclerosis and neurological disease controls. The shallow-sequencing dataset includes lower-depth technical replicate sequencing of discovery-cohort samples and an independent validation cohort. These data were generated to assess the reproducibility of candidate MS-associated DNA methylation differences identified by deep PBAT-seq and to support validation of methylation signatures in CSF immune cells. The study contributes to the characterization of immune regulatory, adhesion, migration and protocadherin-associated epigenetic changes in multiple sclerosis.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001941","title":"Tissue architecture and immune niches govern ctDNA release in colorectal cancer","description":"Circulating tumor DNA (ctDNA) is central to liquid biopsy-based cancer detection, yet its release into the bloodstream varies widely and remains poorly understood. To define the tissue-level determinants of ctDNA shedding in colorectal cancer (CRC), we integrated tumor-informed plasma sequencing with detailed histopathology, immunophenotyping, spatial transcriptomics, and in situ mutation detection in resectable stages (I–III). ctDNA detectability increased with tumor burden, and high ctDNA shedders exhibited a distinct architectural and microenvironmental phenotype characterized by expanded necrotic pseudolumina, frequent epithelial barrier disruption, and dense myeloid infiltration. Spatial profiling revealed stress-associated malignant programs and a myeloid-rich immune-luminal niche. In situ sequencing confirmed plasma-detected mutations within pseudoluminal debris, identifying these structures as focal reservoirs of shed DNA. These findings provide a mechanistic framework linking tissue architecture, immune remodelling, and spatially organized cell death to ctDNA release with implications for refining liquid biopsy applications.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-04T08:22:04.091205+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001942","title":"Single-cell RNA-sequencing of Chlamydia trachomatis-infected human neutrophils","description":"scRNA-seq (10x Genomics 3' v3.1) of human peripheral-blood neutrophils from 3 donors, uninfected or infected with Chlamydia trachomatis (MOI 10), at 0, 6 and 24 h, identifying infection-induced neutrophil states.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001943","title":"MPZL1-associated fibroblast-epithelial crosstalk may contribute to aging-related ovarian epithelial remodeling","description":"we established a direct co-culture system of normal ovarian surface epithelium organoids and fibroblasts to investigate stromal factors associated with ovarian epithelial aging. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001944","title":"Establishment of germline-encoded antibodies during primary dengue infection","description":"This study supports the manuscript “Establishment of germline-encoded antibodies during primary dengue infection” and characterizes longitudinal B cell receptor repertoire dynamics during controlled primary DENV1 infection. Bulk BCR sequencing was performed on whole-blood total RNA from flavivirus-naïve participants in a DENV1 live-virus human challenge study. Samples were collected at days 0, 8, 10, 14, and 28 post-infection, corresponding to pre-infection, early viremic, peak viremic/acute, late viremic/critical-phase, and convalescent timepoints. Libraries were prepared from 1 µg RNA per sample using the NEBNext Immune Sequencing Kit with BCR/IGH-specific amplification and sequenced on an Element Biosciences AVITI system using 300PE chemistry.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-07T15:40:00.681262+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001945","title":"Mutational order shapes cell state and chromatin accessibility during early colorectal cancer evolution","description":"Using CRISPR mediated gene editing in patient-derived human colon organoids, we investigate how mutational order shapes cell state and downstream phenotype. We find that loss of FBXW7 on a wild-type background produces minimal phenotypic or transcriptomic change but induces a subtle shift towards a foetal-like, regenerative stem cell identity. Strikingly, the order of mutation acquisition produces markedly different outcomes. 'FA' organoids (i.e. FBXW7 loss preceding APC mutation) retain a near-normal morphology and transcriptional profile. In contrast, 'AF' organoids adopt a proliferative stem cell state and a more transformed phenotype, despite identical final genotype. These differences were associated with distinct chromatin accessibility landscapes, and reflect a cell state-dependent constraint on the transcriptional consequences of subsequent mutations.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-28T09:03:17.366561+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001946","title":"Patient-derived organoids enable disease modeling and personalized therapy for Pleural Mesothelioma","description":"Pleural Mesothelioma (PM) is an aggressive cancer characterized by high heterogeneity and 5-year-survival rates of <10%. To enable disease modeling and personalized medicine for PM we developed an expandable tumor organoid (tumoroid) system that correctly maintained tumor characteristics and disease heterogeneity, which was validated by bulk RNA-seq of patient tumor samples and organoids. Furthermore, performing scRNA-sequencing and WGS of 2 organoid samples, together with WGS of the corresponding tumor, we demonstrated that intra-tumor heterogeneity of PM was driven by sub-clonal copy number variation (CNV) and plasticity along the epithelioid-sarcomatoid axis.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001947","title":"Effects of nicotinamide riboside in mitochondrial DNA disease","description":"An experimental medicine study was performed in eight individuals with mitochondrial DNA disease. The participants took Nicotinamide Riboside (dose 10mg/kg twice a day) for four weeks. Muscle samples from quadriceps muscle biopsy were analysed by RNA sequencing, proteomics and targeted metabolomics.  Visit 1 was before treatment. Visit 5 was after 4 weeks of treatment.  Please see the publication for further details.","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001948","title":"Viral infections in primary bronchial epithelial cells","description":"Respiratory viral infections, such as those caused by rhinovirus, adenovirus, influenza, respiratory syncytial virus (RSV), and SARS-CoV-2, represent a major global health challenge. Despite extensive research, effective and specific antiviral treatments for these infections are still lacking, with patient care often limited to symptomatic relief. The SARS-CoV-2 pandemic, alongside the emergence of avian flu H1N1 and Nipah virus, has underscored the critical role of the respiratory tract as a critical viral target. Respiratory viral infections exhibit marked variability in infectivity and disease severity across different age groups. The objective of the dataset is to identify transcriptomic responses of the human bronchial epithelium to Adenovirus type 5, rhinoviruses A and C, as well as SARS-CoV-2. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001949","title":"Single-cell RNA-seq to assess the role of RUNX1 in the regulation of immune-like megakaryocytes","description":"In this study, we assess the role of RUNX1 in the emergency and function of iMKs by single cell transcriptomic analysis of MKs derived from induced pluripotent stem cells and from CD34+ of patients or controls. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001950","title":"Cut&Tag to assess the role of RUNX1 in the regulation of immune-like megakaryocytes","description":"In this study, we profiled RUNX1 by CUT&Tag in MKs derived from induced pluripotent stem cells, to characterize modifications and transcription factor occupancy underlying MK emergence and function.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001951","title":"Genomic Characterization of Somatic Mutagenesis and Clonal Evolution in Basal Cell Carcinoma Whole Genome Sequencing (WGS)","description":"This study aims to perform comprehensive whole-genome sequencing of basal cell carcinoma (BCC) to characterize somatic mutagenesis and clonal evolution. We investigate the relationship between TP53 mutational status, replication timing, and the activity of ultraviolet (UV) light-induced mutational signatures. By comparing tumor-normal pairs, we identify genomic drivers and copy number alterations that shape the clinical and geographical heterogeneity of BCC.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001952","title":"Single cell RNASeq data from RA samples after therapy","description":"Single cell RNASeq data from blood samples of 48 RA patients treated with antiTNF, or antiIL6R, or JAK inhibitors, after therapy","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-05T11:03:17.412724+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001953","title":"MonoMac in vitro single cell RNAseq","description":"Transcriptome characterization of macrophages derived from HLA-DRB1 negative and HLA-DRB1 positive monocytes cultivated in vitro","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-05T11:03:20.489916+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001954","title":"DoCTIS longitudinal cohort bulk RNAseq","description":"Longitudinal transcriptomic data from 380 blood samples across six IMIDs treated with multiple targeted therapies.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-05T11:03:23.191226+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001955","title":"A multi-omic approach to liquid biopsy for the management of patients with extra-pulmonary neuroendocrine carcinoma","description":"We analysed 114 QC-passed cfDNA samples from 51 patients with advanced extra-pulmonary neuroendocrine carcinoma (EP-NEC) before and after the start of first-line platinum/etoposide chemotherapy. We applied a multi-omic single workflow, T7-MBD-seq, to profile cfDNA methylation, copy number alterations (CNA) and fragmentomics for biomarker discovery. Comparison of pre-treatment EP-NEC samples with non-cancer control samples in a 52-sample discovery cohort identified 4,284 EP-NEC differentially methylated regions (DMRs) which were validated in an independent cohort of 78 samples. Methylation score (methylation level estimate across DMRs) positively correlated with tumour fraction determined by CNA (ρ=0.88, p<2.2e-16) and ratio of short/long cfDNA fragments (ρ=0.81, p<2.2e-16) corroborating cancer-specific patterns. Differential methylation patterns could distinguish between NECs originating in the gastro-entero-pancreatic tract and the lung (area under the curve (AUC) = 0.972) and between NECs and adenocarcinomas (AUC = 0.963), signposting cfDNA methylation capability to identify NEC tissue of origin and discriminate between histologies.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001956","title":"Wellcome LEAP TNBC cohort raw sequencing data","description":"This study contains controlled-access raw sequencing data from the retrospective Wellcome LEAP triple-negative breast cancer cohort. The data include human patient-derived single-nucleus RNA-seq and 10x Visium spatial transcriptomics generated from pre- and post-treatment tumour samples. The first dataset linked to this study supports the Victori et al. Cell Reports Medicine manuscript and includes raw FASTQ files from the relevant sequencing runs. Because some snRNA-seq libraries were generated from multiplexed pools, some raw FASTQ files may include additional co-multiplexed LEAP samples beyond those directly analysed in that manuscript. Access is controlled through the appropriate LEAP Data Access Committee and policy.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-22T15:12:27.052267+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001957","title":"The evolving genomic landscape of circulating tumor DNA represents an early predictor of immunotherapy response in lung cancer","description":"Circulating tumor DNA (ctDNA) analyses are informative as an early indicator of immunotherapy response in advanced non-small cell lung cancer (NSCLC), however the clinical role of ctDNA molecular response requires further validation. As part of a prospective clinical protocol (NCT05995821), we performed ctDNA (n=328) and matched white blood cell DNA (WBC; n=109) targeted error-correction sequencing from 109 patients with advanced/metastatic NSCLC who received anti-PD-(L)1 as monotherapy or in combination. Following variant cellular origin resolution, landmark molecular response (mR) was defined as undetectable ctDNA within 3-9 weeks of treatment initiation. Among 2,818 plasma variants, 23% were clonal haematopoiesis-related, which confounded driver gene associations with clinical outcomes and molecular responses. Implementing a tumor-naïve WBC DNA-informed approach increased the number of evaluable cases while maintaining the overall accuracy of landmark ctDNA molecular responses. Pre-treatment ctDNA burden but not blood tumor mutation burden predicted survival. A significant enrichment in landmark ctDNA mR was noted among patients with progression-free survival (PFS) ≥6 months with immunotherapy (p=2.5e-05) and chemo-immunotherapy (p=0.02). Patients in the landmark mR group attained longer progression-free (p=1.6e-06) and overall survival (p=2.5e-05) compared to those with molecular progression. Our findings indicate that landmark ctDNA molecular response provides a real-time and accurate approach for monitoring immunotherapy clinical outcomes. Although not currently validated for regulatory use, these findings demonstrate the potential utility of ctDNA as an early endpoint in clinical trials.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-22T14:52:11.430817+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001958","title":"Neoadjuvant immune checkpoint blockade in mismatch-repair proficient colon cancers","description":"Immune checkpoint blockade has led to paradigm shifts in the treatment of various tumour types, yet limited efficacy has been observed in patients with metastatic mismatch-repair proficient (pMMR) colorectal cancer. Here we report an in-depth analysis of patients with early-stage pMMR colon cancer from the phase II NICHE study (ClinicalTrials.gov: NCT03026140). A total of 31 patients received neoadjuvant treatment of nivolumab plus ipilimumab followed by surgery. The response rate was 26% and included six patients with a major pathological response (≤10% residual viable tumour). One patient with an ongoing clinical complete response did not undergo surgery. Responses were observed despite a low tumour mutational burden in all tumours, while chromosomal genomic instability scores were significantly higher in responders compared to non-responders. Responding tumours were more likely to be TP53 mutant, KRASG12 wildtype and had significantly higher baseline expression of proliferation signatures and TCF1. Imaging mass cytometry also revealed a higher percentage of Ki-67+ cancer and Ki-67+ CD8+ T cells in responders compared to non-responders. Meanwhile, in non-responders, we observed an enrichment for an inflamed-fibrotic microenvironment associated with TGF-β expression, hinting towards possible resistance mechanisms. These results provide a comprehensive analysis of response to neoadjuvant ICB in early-stage pMMR colon cancers and identify potential biomarkers for patient selection.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001959","title":"T-cell receptor repertoires against HLA class I-restricted minor histocompatibility antigens are highly diverse with a small subset of public clonotypes","description":"Allogeneic hematopoietic stem cell transplantation (alloHSCT) can be a curative treatment for hematological diseases. After HLA-matched alloHSCT, donor T cells may recognize minor histocompatibility antigens (MiHAs), which are polymorphic HLA-binding peptides on patient cells that are absent from donor cells due to genetic differences. Donor T cells can induce beneficial anti-tumor effects if MiHAs are targeted on malignant hematopoietic cells in the patient, while Graft-versus-Host Disease (GvHD) may develop if MiHAs are targeted on patients’ healthy non-hematopoietic tissues. We previously isolated T-cell clones from patients responding to donor lymphocyte infusions (DLIs) after HLA-matched alloHSCT, and identified HLA class I-restricted MiHAs. To investigate MiHA-specific T-cell responses in patients, we here sequenced the T-cell receptors (TCRs) of MiHA-specific T-cell clones and identified 394 distinct TCRs against 122 MiHAs. We used the collection of identified TCRs to measure frequencies of matched MiHA-specific TCRs in 39 patients responding to DLI with anti-tumor responses accompanied with no (n=9), limited (n=8) or severe (n=22) GvHD. The data showed higher MiHA-specific TCR frequencies in patients with severe GvHD, which were mainly driven by clonal expansion. Moreover, within the diverse MiHA-specific TCR repertoires in these patients, we identified 5 public TCRs against 4 MiHAs with identical CDR3 regions and several TCRs targeting MiHAs with similar, but not identical, CDR3 regions. We demonstrated that patients with severe GvHD have high MiHA-TCR frequencies mainly driven by clonal expansion, and that MiHA-specific TCR repertoires in patients responding to DLI after alloHSCT are highly diverse with a few public clonotypes. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001960","title":"RA Validation Cohort ","description":"In this validation cohort, PBMCs from 32 RA donors have been profiled using scRNA-Seq data","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-10T10:16:47.510095+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001961","title":"Comprehensive Genomic Profiling of Biliary Tract Cancer (BTC)","description":"This study investigates the genomic landscape of biliary tract cancer (BTC) using next-generation sequencing (NGS) mutation profiling data generated from a patient cohort at Asan Medical Center (AMC) and signapore. Tumor samples were characterized by targeted comprehensive genomic profiling to identify somatic alterations relevant to BTC. The dataset supports two complementary research aims: characterization of MTAP alterations and assessment of homologous recombination deficiency (HRD). The overall goal is to identify clinically relevant molecular features and to better understand the mutational characteristics of BTC in this cohort.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001962","title":"Dissecting the sources of variation in neuronally differentiated iPSC lines through multi-omics analysis","description":"Multi-omics analysis for rare neurodevelopmental disorders. The material consists of patient-derived IPSCs from NANS, CDH2, and DM1 patients. In some cases the genotype was rescued using CRISPR/Cas9 gene editing. The studied omics include Genomics, Transcriptomics, DNA methylation, Proteomics, Metabolomics, and Lipidomics.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-30T12:10:32.319146+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001963","title":"Sex-specific molecular signatures in persistent pain after whiplash injury","description":"We conducted whole-blood RNA-sequencing at 6 months post-injury in individuals with WAD grade II (WADII)—the most common clinical presentation, characterised by neck pain and restricted movement without frank neurological signs—to compare transcriptional profiles between recovery groups (persistent moderate/severe vs minimal symptoms).","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-28T13:07:56.170085+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001964","title":"Tumoral immune microenvironment profiling in B-cell non-Hodgkin lymphoma stratifies patients in different prognostic groups","description":"Non-Hodgkin lymphomas (NHL) are heterogeneous B-cell malignancies in which the tumor immune microenvironment (TIM) influences disease progression and has emerging potential for prognostic patient stratification. This project investigates the TIM of NHL by combining multiparameter flow cytometry with targeted DNA sequencing of NHL biopsies. The study aimed to characterize the immune cell composition, immune checkpoint expression, and mutational landscape, and to evaluate their association with clinical and prognostic features across NHL subtypes. The classification of TIM profiles by flow cytometry predicts clinical outcomes in patients with follicular lymphoma (FL), highlighting its potential value for risk stratification and the identification of novel immunotherapeutic targets in NHL.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-05T17:38:55.787009+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001965","title":"Mutant TP53 allelic states in human hematopoietic stem and progenitor cells","description":"Clonal hematopoiesis driven by TP53 mutations is a potent risk factor for diverse human pathologies. By CRISPR/Cas9 engineering of human hematopoietic stem and progenitor cells, we investigate the role of TP53 mutations in induction of chromosomal aberrations by single-cell template strand sequencing.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-30T12:11:27.368322+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001966","title":"RNA-seq of Breast Cancer Cells in Bone-Mimetic Matrices","description":"Bulk RNA sequencing dataset of four breast cancer cell lines (MDA-MB-231, SCP2, MCF7 and BT-4747) cultured in collagen or in collagen-hydroxyapatite (bone mimetic) matrices to model microenvironment-driven gene expression changes.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-30T12:12:21.152947+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001967","title":"SARS-CoV-2 induces robust antiviral innate immunity in PBMCs that is partially mirrored by inactivated virus","description":"The COVID-19 pandemic, caused by SARS-CoV-2, has underscored the importance of understanding viral immunogenicity and pathogenesis in order to develop effective diagnostics, therapeutics, and vaccines. Although studying novel, highly pathogenic viruses requires high-containment facilities, inactivated SARS-CoV-2 provides a non-infectious model to safely investigate various aspects of the immune response induced by the virus. While inactivated SARS-CoV-2 has been shown to evoke immune responses, it remains unclear to what extent these responses mimic those induced by the live virus. In this study, we investigated the in vitro immune response of peripheral blood mononuclear cells (PBMCs) to heat-inactivated and live SARS-CoV-2. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001968","title":"Serafini et al., Nuclear localization of the glutaminyl-tRNA synthetase QARS reveals its role in DNA damage response in ovarian cancer","description":"Uncovering novel mechanisms controlling DNA damage response (DDR) is essential to better understand the molecular features of high-grade serous ovarian cancers (HGSOC), which remain a clinical challenge. Here, we demonstrate that the glutaminyl-tRNA-synthetase QARS is a new key player in DDR. We show that QARS is regulated at translational level by the MAPK pathway in HGSOC and controls homologous recombination (HR) through a translation-independent mechanism. Analyses combining RNA sequencing, immunohistochemistry, proteomic data and functional assays from HGSOC patient cohorts and relevant cellular models reveal that QARS promotes DNA repair via the HR pathway. Interestingly, we uncover that QARS is located in the nucleus and is enriched at chromatin upon DNA damage. Nuclear QARS controls HR by interacting with the nuclear autoantigen SP100, a major component of PML-nuclear bodies (PML-NB), that are regulatory hubs for DNA repair proteins. Our data highlight novel nuclear functions and mechanisms for QARS involving SP100, PML-NB and MRE11 that enhance HR in HGSOC.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-07-27T10:16:02.876967+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001969","title":"RNA-seq from ASCENT cohort","description":"Bulk RNA sequencing data generated from primary resected non-small cell lung cancer (NSCLC) tumour tissue collected through the ASCENT study.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-10T10:02:43.861258+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001970","title":"IMMUcan BC3 cohort","description":"The goal of IMMUcan is to understand how the immune system interacts with tumors and how therapeutic interventions influence this interaction. This cohort includes patients with confirmed localized Her2+ (stages I to III) treated with neo-adjuvant therapy  Comprehensive profiling data are integrated with longitudinally collected clinical information. Cellular profiling of the same tumor samples was performed using multiplex immunofluorescence imaging, imaging mass cytometry, and H&E staining.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001971","title":"TMEM259 alleles modulate respiratory syncytial virus infection and ER-stress-triggered apoptosis","description":"Whole Exome Sequencing data for the IRIS1, IRIS2, and IRIS3 cohorts.\r\nAbstract:\r\nRespiratory syncytial virus (RSV) is a main cause of infant morbidity and mortality. Susceptibility factors for severe RSV bronchiolitis in previously healthy children are unclear.\r\nWe analyze genetic variants in 5,141 genes involved in virus sensing, interferon (IFN) signaling and effector functions in a population of n=101 previously healthy infants with severe RSV bronchiolitis.\r\nComparing the allele frequencies of the patient cohort with the Exome Aggregation Consortium (ExAC) dataset our analysis reveals 94 non-synonymous coding single nucleotide polymorphisms (SNPs) mapping to 79 potential risk genes. Follow up of genes expressed in human lung cells show that TMEM259 (also known as membralin), a protein involved in regulating endoplasmic reticulum (ER) stress and neuronal cell survival, restricts RSV infection. Analysis of engineered human airway cells endogenously expressing the TMEM259 major allele or the rs77868901 minor variant shows allele-dependent modulation of RSV infection and ER-stress induced apoptosis, but not IFN activity nor induction of IFN stimulated genes. TMEM259 abundance and polymorphisms modulate RSV infection likely by modulating the ER stress response and apoptosis. This data may aid future risk stratification and development of prevention and treatment strategies for RSV.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-23T13:14:21.10886+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001972","title":"Malignancy of breast cancer cells is increased in a luminal-hybrid state defined by progenitor markers CD146 and keratin 14","description":"We first analyzed a patient-derived xenograft (PDX)-derived breast cancer cell line by dividing cell populations based on CD146-expression by FACS and found that this marker defines a cellular state with increased expression of a selection of luminal hybrid markers, including KRT14. We then knocked out CD146 or KRT14 in another patient-derived xenograft (PDX)-derived breast cancer cell line to investigate further the role of these markers in the hybrid state. For all these populations, we studied their gene expression by bulk RNA sequencing.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-03T11:40:58.659511+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001973","title":"Single cell RNA-Seq data of PBMCs from IMID samples after therapy","description":"longitudinal single cell transcriptomic atlas of peripheral immune cells from 360 donors responding divergently to targeted therapies, including 11 disease - drug cohorts. We found that while disease imposes a profound reorganization of the immune system, signatures of drug response are highly heterogeneous and context-dependent, involving programs that are independent from the disease's signatures. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001974","title":"Effect of TNFR2 agonism on Treg cells from healthy human donors","description":"To comprehensively define the transcriptional reprogramming induced by TNFR2 agonism, we performed bulk RNA sequencing on Treg cells expanded with isotype control (CtrlVHH) or human TNFR2 agonist","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-14T16:06:06.440282+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001975","title":"Effect of TNFR2 agonism on CD4+ T cells (single-cell level) from healthy and SLE donors","description":"We treated peripheral blood mononuclear cells from healthy donors and systemic lupus erythematosus patients with (i) a human-specific tetravalent VHH-Fc fusion TNFR2 agonist, (ii) isotope control VHH, (iii) an IL2-mutein and  (iv) no treatment for 2 days at 4°C. CD4+ T cells were analyzed by scRNA/TCR-seq, including surface protein measurement (CITE-seq) for CD120b. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-14T16:06:06.440282+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001976","title":"IMC-F106C-101 dose escalation","description":"Brenetafusp is an ImmTAC bispecific (PRAME×CD3) targeting the cancer testis antigen PRAME. In this phase 1 study (NCT04262466), 126 HLA-A*02:01+ patients with advanced solid tumors received weekly IV doses from 0.3-320 mcg. The primary objective was to identify the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D); additional objectives included pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity. Brenetafusp demonstrated manageable safety and preliminary efficacy in PRAME+ tumors. A phase 3 trial in metastatic cutaneous melanoma is ongoing","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-10T10:13:05.268652+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001977","title":"Standardized Molecular Detection of RET and Other Gene Fusions in Thyroid Cancer: A Two-Site Validation Study","description":"This study validated methods for detecting RET gene alterations in thyroid cancer using molecular testing across two institutions. It found that next-generation sequencing (NGS) reliably identified RET fusions, other gene fusions, and key mutations, with confirmation by FISH and RT-PCR. Results showed a high level of agreement between both institutions, demonstrating the accuracy and reproducibility of the testing methods. These findings support the use of standardized NGS-based protocols to identify patients who may benefit from RET-targeted therapies. 60 DNA and 60 RNA has been sequenced by targeted NGS ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-08T13:41:11.037885+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001978","title":"Lothian Birth Cohort 1936 single nuclei RNA sequencing study","description":"14 members of the Lothian Birth Cohort 1936 (LBC1936) were sequenced using the Illumina NextSeq2000 platform. The LBC1936 are a relatively healthy cohort of 1091 individuals who underwent cognitive and medical testing at a mean age of 69.5 (SD=0.8) years. They have since undergone further waves of testing, approximately three years apart.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-05T09:43:18.941527+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001979","title":"SOLTI- Arianna trial","description":"The main hypothesis of the study is that enzalutamide induces a significant proliferative arrest in HR+/HER2-negative breast cancer falling into the PAM50 HER2-E subtype. Patient population included males or pre/post-menopausal women with advanced HR+/HER2- ABC resistant to endocrine therapy, received ENZ 160 mg/day until disease progression. Patients were assigned to different cohorts according to PAM50 intrinsic subtypes identified in the pre-treatment tumor biopsy: Cohort A included pts with HER2-E and Cohort B pts with Luminal A/B tumors. Centralized molecular assessment was done at pre-treatment and C1D15.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-07T12:15:23.622752+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001980","title":"MEK and CDK4/6 inhibitors induce neural differentiation and growth suppression in DICER1-mutated intracranial sarcoma - RNAseq","description":"Bulk RNA sequencing of DICER1-mutant primary intracranial sarcoma patient tumours and preclinical models used in Hosein et al.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001981","title":"Molecular and cellular profiling of malignant fluids from advanced breast and ovarian cancer patients by bulk and single-cell RNA sequencing.","description":"In this study, we analyzed CD45-negative sorted cells from malignant ascites and pleural effusions, together with primary and metastatic tumor specimens from ovarian and breast cancer patients. Here, we analysed bulk transcriptomic analyses for distinct gene expression programs between malignant fluids and solid tumors.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001982","title":"Single-cell RNA sequencing of large B cell lymphoma relapsed after CAR T-cell therapy and in vitro serial killing models","description":"Relapsed/refractory large B-cell lymphoma (rrLBCL) following CAR T-cell therapy remains associated with a poor prognosis. Using single-cell RNA sequencing (scRNA-seq), we characterized the T-cell profiles in 7 post-CAR T rrLBCL and 5 CAR T-naïve rrLBCL, revealing dysfunctional transcriptional features in T cells after CAR T-cell therapy. In addition, the dataset includes T cell profiling of CAR T-cell products and samples obtained after serial killing assays in vitro, performed with or without supplementation with non-IL2Rα agonist pegenzileukin. These analyses demonstrated that IL-2 was the most depleted cytokine following the coculture assay.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-11T08:50:27.773057+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001983","title":"Whole-Exome Sequencing in Two Sisters with Nutcracker-Related Pelvic Venous Congestion Implicates COL6A5 as a Candidate Susceptibility Gene","description":"Nutcracker syndrome (NCS) is usually reported as sporadic, and its genetic susceptibility background remains largely unexplored. Using a pair of biological sisters with NCS-related pelvic venous congestion as an entry point, we combined whole-exome sequencing (WES) with multilayered functional genomic analyses to investigate a shared molecular susceptibility background. Rare protein-altering variants co-carried by both sisters were prioritized using multi-tool in silico pathogenicity prediction and evolutionary conservation analysis, followed by tiered evidence ranking, pathway enrichment, protein association network analysis, and tissue and cell-type expression profiling. Filtering retained 57 co-carried protein-altering variants across 19 genes, predominantly missense substitutions. Tiered evidence ranking identified COL6A5 as the highest-ranked candidate. Both sisters carried two adjacent missense variants affecting the same glycine residue within the triple-helical domain of the type VI collagen α5 chain; the phase of these variants could not be resolved from short-read data. Multiple independent tools concordantly predicted both variants as deleterious, and the residue was highly conserved across vertebrates. Pathway enrichment centered on extracellular matrix and collagen-related processes, and COL6A5 showed its highest expression in fibroblasts, consistent with a role in vessel-wall connective tissue. The two sisters showed concordant clinical phenotypes. COL6A5 emerged as the most biologically plausible shared candidate susceptibility gene, suggesting that connective-tissue and vessel-wall structural susceptibility may contribute to disease expression. These exploratory findings are hypothesis-generating and require independent validation.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001984","title":"Fibrinoid-associated neutrophils promote human placentation","description":"This study investigates how neutrophils are locally adapted at the early human maternal-fetal interface and how they contribute to invasive placentation. Using 10x Genomics Chromium Flex single-cell RNA sequencing of first-trimester decidua basalis, together with cytometry, spatial imaging, and functional co-culture assays, we identified decidual fibrinoid-associated neutrophils (dFANs) within the fibrinoid Rohr’s layer. These cells display a compartment-associated phenotype and secrete MMP-9, which promotes extravillous trophoblast motility and contributes to activation of latent TGF-β. The goal of the project was to define the function of neutrophil reprogramming in early pregnancy and its role in supporting human trophoblast invasion.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-19T14:28:19.658156+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001985","title":"Mechanisms of resistance to pembrolizumab treatment in classical Hodgkin Lymphoma","description":"In this project we are applying whole exome sequencing (WES) on plasma-derived ctDNA samples to identify mutations that drive resistance to pembrolizumab treatment in classical Hodgkin Lymphoma","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-12T14:48:57.149071+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001986","title":"GeDi Longread PacBio sequencing","description":"The Jackson Laboratory Genetically Diverse (GeDi) Human Induced Pluripotent Stem Cell (hiPSC) Resource provides a collection of well-characterized clonal hiPSC lines derived from genetically diverse, healthy male and female donors. These lines and their associated genomic and transcriptomic data are made available for unrestricted academic and commercial research. The initial release includes eight hiPSC lines with whole-genome sequencing, DNA methylation, RNA-seq, and genotyping data, with additional lines and data types to follow. This resource enables studies of how human genetic background and sex influence molecular phenotypes, differentiation potential, and drug responses.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-20T13:08:56.19272+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001987","title":"GeDi Oxford Nanopore sequencing","description":"The Jackson Laboratory Genetically Diverse (GeDi) Human Induced Pluripotent Stem Cell (hiPSC) Resource provides a collection of well-characterized clonal hiPSC lines derived from genetically diverse, healthy male and female donors. These lines and their associated genomic and transcriptomic data are made available for unrestricted academic and commercial research. The initial release includes eight hiPSC lines with whole-genome sequencing, DNA methylation, RNA-seq, and genotyping data, with additional lines and data types to follow. This resource enables studies of how human genetic background and sex influence molecular phenotypes, differentiation potential, and drug responses.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001988","title":"GeDi Bulk RNA-seq from undifferentiated and differentiated cell types","description":"The Jackson Laboratory Genetically Diverse (GeDi) Human Induced Pluripotent Stem Cell (hiPSC) Resource provides a collection of well-characterized clonal hiPSC lines derived from genetically diverse, healthy male and female donors. These lines and their associated genomic and transcriptomic data are made available for unrestricted academic and commercial research. The initial release includes eight hiPSC lines with whole-genome sequencing, DNA methylation, RNA-seq, and genotyping data, with additional lines and data types to follow. This resource enables studies of how human genetic background and sex influence molecular phenotypes, differentiation potential, and drug responses.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-20T13:08:50.724725+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001989","title":"GeDi Short-read genomic processed data through DRAGEN","description":"The Jackson Laboratory Genetically Diverse (GeDi) Human Induced Pluripotent Stem Cell (hiPSC) Resource provides a collection of well-characterized clonal hiPSC lines derived from genetically diverse, healthy male and female donors. These lines and their associated genomic and transcriptomic data are made available for unrestricted academic and commercial research. The initial release includes eight hiPSC lines with whole-genome sequencing, DNA methylation, RNA-seq, and genotyping data, with additional lines and data types to follow. This resource enables studies of how human genetic background and sex influence molecular phenotypes, differentiation potential, and drug responses.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-20T13:08:53.460711+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001990","title":"GeDi DoveTail/HiC","description":"The Jackson Laboratory Genetically Diverse (GeDi) Human Induced Pluripotent Stem Cell (hiPSC) Resource provides a collection of well-characterized clonal hiPSC lines derived from genetically diverse, healthy male and female donors. These lines and their associated genomic and transcriptomic data are made available for unrestricted academic and commercial research. The initial release includes eight hiPSC lines with whole-genome sequencing, DNA methylation, RNA-seq, and genotyping data, with additional lines and data types to follow. This resource enables studies of how human genetic background and sex influence molecular phenotypes, differentiation potential, and drug responses.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-20T13:08:48.096873+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001991","title":"Genomic signatures of recent human adaptation to the Foraging-to-Farming Transition","description":"Human populations across multiple regions transitioned from hunting and foraging to sedentary farming societies starting ~10 to 12kya, narrowing dietary diversity and transforming relationships with animals and pathogens. To investigate how these ecological changes shaped human adaptations, we analyzed high-coverage whole-genome sequence data from 1,092 individuals practicing hunter-gatherer, agriculturalist, and pastoralist lifestyles across eight geographic regions spanning Africa, Asia, and Oceania. Collectively, our findings illuminate the genetic legacy of ecological changes associated with the foraging-to-farming transition and highlight the central role of non-coding regulatory variation in human adaptation.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-24T11:46:08.892472+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001992","title":"scRNA-seq counts","description":"scRNA-seq count matrices for 36 patients used in publication.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-11T08:37:19.966759+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001993","title":"scATAC Gene scores","description":"Gene score matrices generated with ArchR based on chromatin profiles","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-11T08:37:19.966759+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001994","title":"Concordant transcriptomics analysis of the lungs and blood after exposure to diesel exhaust: a randomized, controlled human exposure study","description":"RNAseq on bronchial brushing and peripheral blood samples from mixed population cohort (healthy, ex-smokers, COPD). Approximately 32 participants were exposed to diesel exhaust.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-20T12:53:47.260373+02:00","is_deprecated":false},
{"accession_id":"EGAS50000001995","title":"Transcriptional Dissection of the Clonal Haematopoiesis Bone Marrow Microenvironment reveals altered Niche Signaling","description":"Clonal haematopoiesis (CH) is a preleukemic condition common in ageing, where blood stem cells (HSCs) acquire somatic mutations conferring a clonal advantage. CH increases the risk of acute myeloid leukaemia and cardiovascular disease. It remains unclear how CH clones gain a selective advantage, leading to clonal expansion. While mouse models link age-associated inflammation to mutant clone expansion, the role of the stromal bone marrow microenvironment (BM niche) has scarcely been studied. To investigate BM niche alterations in human CH, we developed a protocol to generate high-quality scRNAseq data from non-hematopoietic cells isolated from BM aspirates (Marrow) and enzyme-digested solid bone (Endosteum) of donors undergoing hip arthroplasty. We analysed 28,652 cells from 7 individuals with DNMT3A- or TET2-mutated CH and 5 age-matched controls. We identified two endothelial and 13 stromal cell populations in all donors. In CH samples virtually all stromal cell populations showed significant downregulation of gene signatures related to OXPHOS, translation and MYC activity, suggesting a metabolic shift towards an energy-conserving, non-proliferative state. We observed pronounced compositional changes in TET2mut CH stroma but only very modest changes in DNMT3Amut CH BM. Further, we identified a subset of CXCL12high-expressing MSCs (CAR MSCs) which expressed IFN-activation signatures and significantly expands in CH. These iCAR MSCs are the highest producers of HSC support factors and can be found in other haematological conditions suggesting they are a counter mechanism to protect healthy haematopoiesis under stress. Our data reveal distinct remodelling of the stromal BM niche in human CH, with altered cellular composition, metabolic states, and signalling capacity. These findings show that niche dysfunction may contribute to the selective advantage and expansion of mutant HSC clones.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001996","title":"Single cell profiling of non-haematopoetic cells in the human bone marrow microenvironment","description":"To establish an optimized method for single cell trancriptome profiling of stromal cells from human bone marrow and bone we compared the 10X Chromium and BD Rhapsody platforms for scRNA sequencing of non-haematopoetic cells from 3 donors. We found that the BD Rhapsody approach was able to capture a purer population of non-heamatopoetic cells with a higher number of genes per cell.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001997","title":"Disruption of skin homeostasis reveals divergent reconstitution dynamics of human skin tissue-resident memory T cell subsets","description":"Tissue-resident memory T cells (TDRM) regulate homeostasis and inflammation, yet their maintenance and functional adaptation in humans remain poorly understood. Here, we study dynamic changes in human skin TDRM in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT), with or without graft-versus-host disease (GVHD).\r\nWe generated a high-dimensional, time-, tissue-, genotype-, and clonotype-resolved single-cell RNA and T cell receptor (TCR) sequencing dataset comprising longitudinal samples from 12 patients following HSCT and acute GVHD. The data are provided as aligned BAM files. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001998","title":"shallow whole genome sequence (sWGS) of esophageal adenocarcinoma (EAC)","description":"This study looks at genome-wide features from 132 longitudinal plasma samples from 49 patients with EAC, from Canada. Cell-free DNA extracted from plasma samples was sequenced on Illumina NextSeq 2000 Sequencing System","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000001999","title":"Targeted sequencing of esophageal adenocarcinoma (EAC)","description":"This study looks at somatic and germline mutations from 82 longitudinal plasma samples from 49 patients with EAC, from Canada, using targeted sequencing with a 127-gene pane. Samples were sequenced on an Illumina NovaSeq 6000 Sequencing System ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002000","title":"Genetic analysis of paired diagnosis and relapse neuroblastomas","description":"Neuroblastoma is the most common extracranial paediatric solid tumour. Patients with high-risk neuroblastoma often relapse, with a dismal chance of survival (<10%). Here we studied 38 paired diagnosis or post-chemotherapy and relapse neuroblastoma cases from all risk groups to elucidate the genetic basis of relapse. We assessed structural variations, mutational data and in a subset clonal evolution. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002001","title":"Characterization of cell types, positional codes, and enhancers contributing to human facial individuality and pathology","description":"Human genetic diversity generates an astonishing variety of facial shapes, and craniofacial anomalies rank among the most common birth defects. This study generated a multimodal atlas of human embryonic craniofacial development across embryonic weeks 6–11, including single-cell transcriptomics, chromatin accessibility, and spatial transcriptomics. The dataset characterizes cell states, mesenchymal subtypes, and their gene-enhancer cis-regulatory landscapes in space and time. These data provide a resource for studying normal human facial development, craniofacial abnormalities, and the genetic mechanisms underlying facial individuality.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-06T09:40:18.957945+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002002","title":"Cord blood DNA duplex sequencing libraries using deepDLP","description":"As part of the DeepClone protocols paper we used three cord blood samples to validate the error rate of deepDLP duplex library preparation method. The FASTQs shared below correspond to these three cord blood samples.\r\nWith this data we concluded that the error rate of the technology is between 1 and 3x10-8 errors per sequence basepair.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-04T16:31:17.211974+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002003","title":"Spatial transcriptome profiling of breast cancer","description":"Breast cancer presents diverse subtypes, with distinct molecular profiles. Understanding the differences between breast cancer subtypes is essential to unravel the molecular mechanisms that drive heterogeneity. We present a spatial transcriptomics dataset generated from 15 human breast cancer tissues representing two distinct subtypes. This resource provides a spatially-resolved transcriptomic profile that captures subtype-specific gene expression patterns and tumor microenvironment features. This dataset can serve as a reference for studies on breast cancer heterogeneity.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002004","title":"Early embryonic somatic mosaicism and hypermutation in Fanconi anemia","description":"This study investigates early postzygotic somatic mosaicism and hypermutation in individuals with Fanconi anemia using high-coverage family trio whole-genome sequencing. The project aims to characterize mosaic SNVs and indels arising during early human embryogenesis and to compare patterns across Fanconi anemia complementation groups involving DNA repair genes.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002005","title":"Exploring the biliary microbiota in obese and non-obese patients with symptomatic gallstones","description":"Recent advances in metagenomics have expanded our ability to detect low-abundance microbial communities. While the gut remains the most densely populated microbial habitat, emerging evidence has proposed that microorganisms might also inhabit anatomical sites once considered sterile, such as the biliary system. We apply next-generation DNA sequencing to characterize the bacterial community of bile in obese and non-obese patients with symptomatic gallstones. Bile samples were collected from 64 patients (32 obese, 32 non-obese) undergoing elective cholecystectomy. We incorporated negative (sterile tubes) and positive (mock microbial community standard) controls to evaluate contamination risks. We applied both 16S rRNA gene amplicon and shotgun metagenomic sequencing. Both sequencing methods detected extremely low bacterial biomass in bile. Specifically, shotgun metagenomic sequencing identified bacterial DNA traces in only 8 samples, displaying minimal community similarity. In the positive controls our measurements confirmed the expected microbial community composition and in the negative controls no bacterial DNA was detected. In contrast, 16S rRNA gene sequencing showed bacterial DNA in all bile samples as well as in negative controls, suggesting a higher susceptibility to contamination. Our findings suggest that bile may not be consistently colonized by bacterial communities in uncomplicated gallstone disease ","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-10T09:58:57.593676+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002006","title":"Enzymatic Methylation Sequencing of 16 MRTs","description":"Malignant rhabdoid tumors (MRTs) are extremely rare and highly aggressive pediatric cancers with 5-year event-free survival rates below 20%. Utilizing integrated genomic, transcriptomic, and epigenomic profiling of 16 patient-derived MRTs, our aims are to refine the molecular definition of MRTs, uncover potential therapeutic vulnerabilities, and highlight the potential of PARP-targeted strategies in the pursuit of more effective and less toxic treatments.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002007","title":"Whole Genome Sequencing of 16 MRTs","description":"Malignant rhabdoid tumors (MRTs) are extremely rare and highly aggressive pediatric cancers with 5-year event-free survival rates below 20%. Utilizing integrated genomic, transcriptomic, and epigenomic profiling of 16 patient-derived MRTs, our aims are to refine the molecular definition of MRTs, uncover potential therapeutic vulnerabilities, and highlight the potential of PARP-targeted strategies in the pursuit of more effective and less toxic treatments.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002008","title":"RNA Sequencing of 16 MRTs","description":"Malignant rhabdoid tumors (MRTs) are extremely rare and highly aggressive pediatric cancers with 5-year event-free survival rates below 20%. Utilizing integrated genomic, transcriptomic, and epigenomic profiling of 16 patient-derived MRTs, our aims are to refine the molecular definition of MRTs, uncover potential therapeutic vulnerabilities, and highlight the potential of PARP-targeted strategies in the pursuit of more effective and less toxic treatments.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002009","title":"Type 1 interferon perturbates clonal competition by reshaping human blood development","description":"We studied hematopoietic stem cells, progenitors and immune cells from patients with myeloproliferative neoplasms (MPN) at baseline and following interferon-⍺ (IFN⍺) treatment, the only therapy to deplete mutated stem cells. We deployed single-cell multi-omics methods that distinguish the IFN⍺ effects on mutated stem cells from the admixed wildtype HSCs, with respect to their differentiation, transcriptomes, immunophenotypes, and chromatin accessibility.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-05T10:34:00.18281+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002010","title":"IMMUcan SYNERGY BC1 cohort","description":"The goal of IMMUcan is to understand how the immune system interacts with tumors and how therapeutic interventions influence this interaction. This cohort includes patients with advanced or metastatic triple-negative breast cancer (TNBC) treated with first-line chemo-immunotherapy trial of durvalumab, paclitaxel, and carboplatin with or without the anti-CD73 antibody oleclumab enrolled in the SYNERGY trial. Comprehensive profiling data are integrated with longitudinally collected clinical information. Cellular profiling of the same tumor samples was performed using multiplex immunofluorescence imaging, imaging mass cytometry, and H&E staining.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-12T14:39:56.71894+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002011","title":"Ex vivo therapy-driven selection of glioblastoma stem-like cells models resistance evolution","description":"Glioblastoma (GBM) remains lethal, creating an urgent need for experimental models of therapy-\r\nspecific resistance evolution. Within-patient GSC models were developed by parallel ex-vivo selection\r\n\r\nunder temozolomide (TMZ-GSC) or ionizing radiation (IR-GSC), alongside untreated controls (CTRL-\r\nGSC).\r\n\r\n• O6-methylguanine-DNA methyltransferase (MGMT) expression was confirmed as a\r\ndeterminant of primary TMZ resistance and was maintained during GSC evolution.\r\n• In MGMT-negative GSCs, primary TMZ sensitivity evolved into stable secondary resistance\r\nthrough mismatch-repair gene inactivation, recapitulating patient findings, or was retained\r\nalong with a newly identified drug-tolerant phenotype.\r\n• Primary radioresistance was commonly observed, while its further evolution was associated\r\n\r\nwith more efficient DNA double-strand-break repair and enrichment of homologous-\r\nrecombination and checkpoint-control transcriptional programs.\r\n\r\n• In GSCs emerging after either TMZ or IR, broad transcriptional patient-specific programs and\r\nclassification-relevant subtypes were largely preserved.\r\n• Across treatments, GSC evolution was accompanied by shared genome-maintenance and\r\nmitotic chromosome-segregation transcriptional programs and increased RTK expression and\r\nactivity, collectively promoting recovery after genotoxic stress.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-24T09:51:01.216975+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002012","title":"FGFR2b Prevalence in Biliary Tract Cancers","description":"Patients with intrahepatic cholangiocarcinoma (iCCA) often have limited effective treatment options after first-line therapy. Actionable driver mutations are present in only a small subset of patients with iCCA; therefore, therapeutic strategies such as antibody–drug conjugates (ADCs) that do not exclusively rely on presence of specific oncogenic mutations may be particularly attractive. However, there is a critical lack of knowledge regarding prevalent and actionable cell-surface targets in iCCA. We applied a novel isoform-resolved proteogenomic discovery framework for profiling cell surface targets and identified FGFR2b, a splicing isoform of FGFR2, as a therapeutic target in iCCA that is highly-expressed, tumor-enriched, localized to the membrane, and associated with prognosis. FGFR2b is the dominant isoform in iCCA, and it was present in all patients with FGFR2 fusions. These findings provide a strong rationale for further research and therapeutic development of FGFR2b-targeted biologics, including therapeutic antibodies and ADCs, in iCCA. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-05T10:36:12.485188+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002013","title":"Reticulated Platelets Across Coronary Syndromes [Acute Coronary Syndrome] - TotalRNA","description":"totalRNA-seq data of reticulated platelets and mature platelets in acute coronary syndrome ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-05T10:55:45.597148+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002014","title":"Reticulated Platelets Across Coronary Syndromes [Acute Coronary Syndrome] - smRNA","description":"smRNA-seq data of reticulated platelets and mature platelets in acute coronary syndrome ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-05T10:55:45.597148+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002015","title":"Reticulated Platelets Across Coronary Syndromes [Chronic Coronary Syndrome] - TotalRNA","description":"totalRNA-seq data of reticulated platelets and mature platelets in chronic coronary syndrome ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-05T10:55:45.597148+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002016","title":"Reticulated Platelets Across Coronary Syndromes [Chronic Coronary Syndrome] - smRNA","description":"smRNA-seq data of reticulated platelets and mature platelets in chronic coronary syndrome ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-05T10:55:45.597148+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002017","title":"Serum HBsAg cannot distinguish cccDNA activity from integrated HBV DNA expression in chronic hepatitis B virus infection","description":"Total RNA was extracted from the liver biopsies of people with chronic Hepatitis B and sunjected to long-read RNA-seq (Nanopore). The aim of the experiment was to demonstrate expression of full-length chimeric transcripts (produced from integrated HBV DNA) encoding HBV PreS1, PreS2 and S proteins.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002018","title":"A nationwide prospective randomized trial for diagnosing developmental disorders demonstrates  whole-genome sequencing outperforms whole-exome sequencing.","description":"Whole-exome (WES) or whole-genome (WGS) sequencing are recommended as first- or second-tier \r\nmolecular tests for patients with developmental disorders (DD), but the clinical utility of WGS continues \r\nto be debated. This prospective randomized trial involving all Belgian Human Genetics centers \r\ncompared the standard of care (SoC) - combining WES and microarray or shallow WGS - with WGS for \r\n567 individuals with unexplained DD. The diagnostic yield of WGS was 39.8% (113/284) vs 30% for SoC \r\n(85/283) (p=0.015), mainly due to an increased detection of single nucleotide variants and indels \r\n(+8.7%). WGS also enabled the detection of three non-coding (potential) pathogenic variants. \r\nDiagnostic yield was higher for females (45.5%, 97/213) compared to males (28.5%, 101/354) \r\n(p<0.001). De novo variants were found for 23.6% of patients. Analysis of inherited variants in genes \r\nassociated with autosomal dominant phenotypes contributed more to the diagnostic yield (3.9%) than \r\nX-linked variants (1.9%), and to a similar extent as autosomal recessive variants (4.1%). This nationwide \r\nstudy demonstrates WGS outperforms WES for the diagnosis of patients with DD in a decentralized \r\nhospital setting and well-characterized cohort. The results also highlight the importance of evaluating\r\nautosomal dominant inherited variants in genomics analyses for DD.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-06T12:15:15.216618+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002019","title":"Window-of-opportunity trial of olaparib and durvalumab before standard neoadjuvant chemotherapy for stage II/III triple-negative or ER-low breast cancer (MEDIOLA WOO): whole-exome and transcriptome profiling of serial tumor biopsies","description":"The MEDIOLA window-of-opportunity (WOO) trial (ESR-16-11923; NCT03594396) was a single-arm, non-randomized, open-label study conducted at Seoul National University Hospital in 54 female patients with stage II/III triple-negative or estrogen receptor (ER)-low breast cancer. Patients received olaparib 300 mg twice daily for 4 weeks with a single 1500 mg dose of durvalumab on day 15, followed by standard neoadjuvant chemotherapy. The primary objective was to characterize changes in tumor biology through serial biopsies obtained at baseline, day 14 (on-treatment 1; OT1, after olaparib alone and before durvalumab), and day 29 (on-treatment 2; OT2, after olaparib plus durvalumab).\r\nThis study comprises two sequencing datasets. Whole-exome sequencing was performed on baseline tumor biopsies with matched peripheral-blood germline DNA from all 54 patients (54 tumor-normal pairs). RNA sequencing was performed on fresh-frozen serial tumor biopsies, yielding 160 libraries (baseline n = 54, OT1 n = 54, OT2 n = 52; two patients did not undergo OT2 biopsy). All libraries were sequenced on an Illumina NovaSeq 6000 platform. Raw sequence data are provided here under controlled access; processed RNA-seq quantification files are available through the Gene Expression Omnibus.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-13T10:13:36.961951+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002020","title":"UNICORN trial ST","description":"Visium HD fastq files ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-10T16:47:14.053713+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002021","title":"Hypoxia as a Spatial Organizing Principle of Tumor Evolution in Posterior Fossa Subependymoma ","description":"Hypoxia is a key environmental factor in tumors, known to shape functional niches and modulate the tumor microenvironment. Emerging evidence from high-grade gliomas and supratentorial ependymomas indicates that hypoxic regions display a strikingly higher degree of spatial organization compared to normoxic areas, suggesting that hypoxia actively imposes malignant tissue architecture in neuroepithelial tumors. However, it remains unclear at what stage this organization emerges, and whether it reflects an adaptive consequence of tumor progression or already contributes to malignant transformation in earlier states. \r\nTo interrogate this relationship, we profiled 27  posterior fossa subependymomas (PF-SE) by single nucleus, bulk and spatial transcriptomics, alongside a comparative cohort of 5 posterior fossa type A (PF-A) and 6 type B (PF-B) ependymomas. PF-SE is uniquely suited to this question. Although it constitutes a single epigenetically defined molecular subgroup, these tumors span a continuous morphological spectrum ranging from indolent subependymoma to high-grade ependymal differentiation that may appear focally admixed in the same tumor or expand to encompass the entire lesion. This provides an ideal framework to examine whether hypoxia-driven spatial organization is already initiated in lower grades and, if so, how it scales with increasing malignancy.\r\nOur findings demonstrate that the histological spectrum of PF-SE is accompanied by a transition from disorganized tumor compartments toward spatially structured, hypoxic-inflammatory niches. Simultaneously, immune profiling revealed a progressive shift from pro-inflammatory populations toward immunosuppressive, hypoxic tumor-associated macrophages. Our results highlight hypoxia as a unifying mechanism linking tumor architecture, transcriptional adaptation, and immune modulation. Consequently, this work provides a conceptual framework for understanding progression and identifying shared therapeutic vulnerabilities across ependymal tumor entities. \r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002022","title":"Genetic, epigenetic and fragmentomic profiling of plasma cell-free DNA in cancer patients","description":"The primary goal of the study is to explore the temporal changes in cfDNA profiles in liver cancer patients undergoing therapeutic treatment. Serial blood collection and plasma cfDNA analysis were performed in patients with liver cancer, including patients with primary hepatocellular carcinoma, or those with secondary liver metastasis. Various molecular features of cfDNA were studied, including tumor fraction, epigenetic and fragmentomic analysis. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-24T09:48:58.43145+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002023","title":"Distinct mechanisms of CNV formation at the human 15q13.3 locus","description":"The human chromsome 15q13.3 locus is one of the most unstable genomic regions of the human genome and leads to recurrent disease, but the molecular underpinnings of this instability is poorly understood. We generated long-read sequencing data for 10 patient-parent trios carrying 15q13.3 CNVs to resolve CNVs at basepair precision and identify sequence properties that predispose to CNV formation. ","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-16T10:26:12.58767+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002024","title":"Impact of ligand independent ERβ signaling on human Th17 cell differentiation","description":"Sex hormone receptor signaling has been implicated in the female sex bias found in many autoimmune conditions, including Systemic lupus erythematosus (SLE). Estrogen Receptor beta (ERβ) is expressed in T lymphocytes, and its expression is reduced in active SLE, suggesting a potential role in immune regulation. Here, we investigate the function of ERβ signaling in human T-cells and define its contribution to pathogenic T-cell phenotypes associated with SLE. We used a pharmacological inhibitor approach (PHTPP) to assess the role of ligand-independent ERβ signaling in human in vitro Th17 cell differentiation and compare results to transcriptional changes in Th17 cells in SLE. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-28T13:08:39.204242+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002025","title":"Orthotopic Patient-Derived Organoid Model Reveals Tumor Microenvironment-Dependent Phenotypes in Lung Squamous Cell Carcinoma-WTS","description":"RNAseq data","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-28T09:40:09.163774+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002026","title":"Orthotopic Patient-Derived Organoid Model Reveals Tumor Microenvironment-Dependent Phenotypes in Lung Squamous Cell Carcinoma-WGS","description":"WGS","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-28T09:40:09.163774+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002027","title":"Orthotopic Patient-Derived Organoid Model Reveals Tumor Microenvironment-Dependent Phenotypes in Lung Squamous Cell Carcinoma-WES","description":"WES data","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-28T09:40:09.163774+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002028","title":"IMMUcan RCC cohort","description":"The goal of IMMUcan is to understand how the immune system interacts with tumors and how therapeutic interventions influence this interaction. This cohort includes patient with confirmed metastatic RCC, naïve of treatment in the metastatic settings, to be treated in 1st line. Comprehensive profiling data are integrated with longitudinally collected clinical information. Cellular profiling of the same tumor samples was performed using multiplex immunofluorescence imaging, imaging mass cytometry, and H&E staining.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002029","title":"A Comparative Analysis of Illumina, Element Biosciences, and Ultima Genomics Platforms for Liquid Biopsy Applications in Pancreatic Ductal Adenocarcinoma","description":"This dataset contains ultra-deep targeted cfDNA sequencing from plasma samples of four patients with pancreatic ductal adenocarcinoma and 12 healthy controls. Libraries targeting 66 PDAC-associated genes were sequenced using Illumina NovaSeq X Plus, Element Biosciences AVITI, and Ultima Genomics UG 100 to compare platform performance for fragmentomic profiling and low-frequency variant detection.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-28T13:09:23.381739+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002030","title":"Whole genome sequencing of aggressive HIV-associated lymphoma","description":"In this study, 6 aggressive HIV-associated lymphomas were subjected to whole genome sequencing. The dataset includes four Burkitt lymphomas and 2 diffuse large B cell lymphomas. The aim of the project was to identify genetic patterns, e.g. recurrent mutations, that are unique to HIV-associated lymphomas and distinguish them from their counterparts in HIV-negative patients.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002031","title":"Whole exome sequencing of aggressive HIV-associated lymphoma","description":"In this study, 20 aggressive HIV-associated lymphomas were subjected to whole exome sequencing. The dataset includes four plasmablastic lymphomas and 16 diffuse large B cell lymphomas. The aim of the project was to identify genetic patterns, e.g. recurrent mutations, that are unique to HIV-associated lymphomas and distinguish them from their counterparts in HIV-negative patients. The exome sequencing panel used was the Twist WES panel.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002032","title":"Bulk RNA Sequencing of 112 Bladder Cancer Tumor Samples Using Lexogen QuantSeq 3′ mRNA-Seq","description":"Bulk RNA sequencing dataset comprising tumor samples from 112 bladder cancer patients. Gene expression profiling was performed using the Lexogen QuantSeq 3′ mRNA-Seq library preparation protocol, which generates strand-specific 3′ end transcript libraries for digital gene expression quantification. The dataset provides transcriptomic profiles for molecular characterization of bladder cancer and supports studies of tumor biology, biomarker discovery, and clinical outcome associations.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-28T13:05:35.004003+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002033","title":"Clonotypic characterization defines B‐cell drivers of clonal expansion and intratumor heterogeneity in IgM monoclonal gammopathies  ","description":"Dataset accompanying the study entitled “Clonotypic characterization defines B‐cell drivers of clonal expansion and intratumor heterogeneity in IgM monoclonal gammopathies” (Moreno, Nadeu, et al. HemaSphere 2026), which includes genomic, epigenomic, and transcriptomic analyses of smoldering and symptomatic Waldenström macroglobulinemia (SWM and WM, respectively) as well as IgM monoclonal gammopathy of undetermined significance (MGUS). ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-01T14:28:58.842161+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002034","title":"Patient-specific CAR T cell barriers in colorectal cancer identified by phenotypic screening of tumor organoids ","description":"This study used CAR-T cells in coculture with patient-derived organoids to model patient-specific responses to CAR-T cell therapy. Heterogeneous killing efficiencies together with downstream analysis revealed tumor-intrinsic drivers of CAR-T resistance. In addition, drug library screens for synthetic lethality identified possible targets for combinatorial treatment strategies.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-28T14:05:05.956345+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002035","title":"Chromosomal mutational signatures of DNA damaging agents at single cell resolution","description":"The chromosomal scale mutational spectrum of small molecules that interact with DNA has been hard to study at scale, as mutational events are distributed in location and occur in parallel in different cells. Here, we present a framework that pairs phylogenetic ancestry reconstruction with mutational signature decomposition to characterise recent, cell-private CNA mutational processes at single-cell resolution. We used this framework to characterize the cell-wise “foreground” of contemporaneous CNAs induced by strand-break inducing chemotherapeutic drugs of different mechanisms. We demonstrate that platinum salts, G-quadruplex stabilizers and topoisomerase II inhibitors, although mechanistically distinct, converge on a mutational signature dominated by telomere-bounded copy-number gain and losses. This signature is observed in different genetic backgrounds and in vivo, in drug treated patient derived-xenograft tumours. We also observe a high rate of endogenous telomere-bounded mutational foreground in BRCA1 deficient cells. We show that the single cell genome derived signature exposures are drug dose-dependent, and use this to identify the decay of mutational load after drug withdrawal. We observe that both cisplatin and a G4 binder molecule (CX5461) exhibit foreground mutational signature persistence up to 3 weeks after drug withdrawal, suggesting that residual effects of exposure may last longer than anticipated. Finally, extending the framework to serially drug-treated patient-derived xenograft (PDX) models, we show that telomere-bounded CNA signature exposure is associated with tumour response across and resistance states exhibit only background levels of mutational signatures. This is consistent with loss of mutational activity on the genome, as opposed to acquired tolerance to chromosomal mutations as a mechanism for some forms of chemotherapeutic drug resistance. Together our results show that scWGS can identify contemporaneous chromosomal mutation patterns induced by small molecules in human tissues.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-13T17:00:05.432304+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002036","title":"Spatial atlas of diffuse large B-cell lymphoma","description":"We leveraged highly multiplexed, single-cell–resolution spatial transcriptomics, bulk RNA sequencing, and tumor–germline paired whole-exome sequencing to profile 465 diffuse large B-cell lymphoma (DLBCL) tumors and define the assembly of 60 lymphoma microenvironment (LME) cell subsets and 5 tumor B cell states into conserved spatial niches and communities that resemble non-malignant lymphoid architecture. Three distinct LME-enriched communities were assembled from combinations of niches and reflected recently described LME archetypes with conserved spatial biology. Tumor B cells were enriched in three B communities harboring distinct, developmentally linked, transcriptional states associated with divergent cell-cell communication (CCC) pathways. Intratumoral heterogeneity in B communities was pervasive across patients and largely unlinked with molecular subtype. Combinations of B communities, rather than single states, were associated with patient outcome, implicating microenvironment-associated tumor B cell transcriptional plasticity in the biology and clinical behavior of DLBCL.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-19T14:51:49.634005+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002037","title":"Spatial atlas of diffuse large B-cell lymphoma","description":"We leveraged highly multiplexed, single-cell–resolution spatial transcriptomics, bulk RNA sequencing, and tumor–germline paired whole-exome sequencing to profile 465 diffuse large B-cell lymphoma (DLBCL) tumors and define the assembly of 60 lymphoma microenvironment (LME) cell subsets and 5 tumor B cell states into conserved spatial niches and communities that resemble non-malignant lymphoid architecture. Three distinct LME-enriched communities were assembled from combinations of niches and reflected recently described LME archetypes with conserved spatial biology. Tumor B cells were enriched in three B communities harboring distinct, developmentally linked, transcriptional states associated with divergent cell-cell communication (CCC) pathways. Intratumoral heterogeneity in B communities was pervasive across patients and largely unlinked with molecular subtype. Combinations of B communities, rather than single states, were associated with patient outcome, implicating microenvironment-associated tumor B cell transcriptional plasticity in the biology and clinical behavior of DLBCL.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-19T14:51:48.072222+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002038","title":"Cell-free DNA methylation profiling in classic Hodgkin lymphoma using cfEM-seq","description":"Genome-wide DNA methylation profiling using cfEM-seq and Ultima Genomics sequencing in classic Hodgkin lymphoma. The study includes plasma-derived cell-free DNA from patients with classic Hodgkin lymphoma together with classic Hodgkin lymphoma and anaplastic large cell lymphoma cell lines. The deposited data comprise original sequencing CRAM files and associated sequencing-provider QC metadata.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-05T14:11:56.114616+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002039","title":"Single-cell RNA and TCR sequencing of ASCENT diagnosis PBMCs","description":"This study characterises peripheral blood CD4 T cell states and T cell receptor clonotypes in participants from the ASCENT cohort at the diagnosis time point. PBMC samples from five participants were profiled using 10x Genomics single-cell gene expression sequencing together with paired T cell receptor V(D)J sequencing. The data were used to investigate circulating regulatory CD4 T cell phenotypes and their clonal relationships in the context of lung cancer.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002040","title":"Transcriptomic profiling of human fibroblasts and fibroblast-derived induced neurons (F-iNs) from SPG4-HSP patients and controls, with and without davunetide treatment","description":"Fibroblast-derived induced neurons (F-iNs), generated by direct conversion of fibroblasts, retain donor-specific epigenetic aging signatures and therefore provide an attractive model for studying age-related neurodegenerative disorders. Here we applied F-iNs to model SPG4-associated hereditary spastic paraplegia (SPG4-HSP), a rare motor neuron disease. This dataset comprises RNA sequencing of transduced fibroblasts and of F-iNs derived from SPG4-HSP patients and healthy controls, with F-iNs analyzed both untreated and following treatment with davunetide, a novel compound with neuroprotective properties.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002041","title":"Comparison of the transcriptomic profile of CD34+ cells of transformed myelofibrosis patients vs non-transformed MF patients (bulk RNA-seq).","description":"46 samples of MPN patients were processed. 1 sample is a pooled patients of 2 donors. This study contains bulk RNAseq. Samples were taken at the time of the MPN diagnosis. Some samples are known to have developped AML after the MPN diagnosis.\r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002042","title":"The transcription factor FOXA2 is a central regulator of human gastric foveolar cell lineage specification","description":"Foveolar cells are essential for maintaining gastric epithelial homeostasis, yet the transcriptional regulators governing their differentiation remain poorly understood. The goal of this study is to identify the molecular mechanisms controlling human gastric foveolar cell differentiation using human adult stem cell-derived gastric organoids. To achieve this, we integrate CRISPR/Cas9 screening with bulk RNA-seq, single-cell RNA-seq, ATAC-seq, and CUT&RUN to identify and functionally characterize transcription factors regulating lineage specification. This approach identified FOXA2 as a master regulator of human gastric foveolar cell differentiation.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002043","title":"RNASeq from ASTEROID biopsy samples","description":"ASTEROID Phase 1 trial of combination IAP inhibitor ASTX660 and pembrolizumab. Tumour biopsies taken before and after 7-day run-in of ASTX660 were sequenced.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-25T14:14:51.631329+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002044","title":"Whole Exome Sequencing","description":"ASTEROID Phase 1 trial of combination IAP inhibitor ASTX660 and pembrolizumab. Matched tumour biopsies and PBMCs were sequenced.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-25T14:14:54.932723+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002045","title":"DKTK Organoid Platform: A multicentric living biobank for functionalizing patient-derived organoids and model clinical outcomes","description":"To enable the generation of harmonized and well annotated PDTO cohorts across national institutions, the German Cancer Consortium (DKTK) has established the Strategic Initiative Organoid Platform. For the MetPredict cohort, individual PDTOs were generated from spatially distinct liver metastases of colorectal cancer. To study the molecular inter-metastatic heterogeneity, samples were submitted to whole exome sequencing.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-28T14:05:08.965624+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002046","title":"A preinvasive regulatory T cell axis for lung cancer interception","description":"This study investigates immune changes associated with the development, persistence and progression of pre-invasive lung squamous lesions. Single-cell RNA sequencing and paired T cell receptor sequencing were performed on bronchoscopic lung samples and peripheral blood collected through the UCLH bronchoscopy surveillance study, including normal and dysplastic tissue samples. The study aims to define immune cell states, tissue-blood T cell clonal relationships and mechanisms relevant to lung cancer interception. The data provide a resource for understanding immune regulation during the transition from premalignancy towards invasive lung cancer.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002047","title":"Mechanisms of resistance to pembrolizumab treatment in a patient with classical Hodgkin Lymphoma","description":"In this project we are applying whole exome sequencing (WES) on plasma-derived ctDNA samples to identify mutations that drive resistance to pembrolizumab treatment in classical Hodgkin Lymphoma","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002048","title":"Single-Cell Multiomic and Whole-Genome Profiling of Primary and Metastatic Colorectal Cancer","description":"This study contains controlled-access single-cell multiomic sequencing (scRNA-seq and scATAC-seq) data generated from patients with colorectal cancer, including 33 primary tumours, 11 metastatic lesions, and 7 adjacent normal tissue samples. Whole-genome sequencing (WGS) data are available for the tumour samples. These data were generated to investigate the genomic and epigenomic landscape of colorectal cancer and to identify recurrent regulatory alterations associated with tumour progression and metastasis.\r\n","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-17T17:06:43.989577+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002049","title":"IMMUcan UroCCR RCC cohort","description":"The goal of IMMUcan is to understand how the immune system interacts with tumors and how therapeutic interventions influence this interaction. This cohort includes samples from UroCCR, the French Research Network on Kidney Cancer, a multi-institutional database established to advance the understanding and treatment of kidney cancer. Comprehensive profiling data are integrated with longitudinally collected clinical information. Cellular profiling of the same tumor samples was performed using multiplex immunofluorescence imaging, imaging mass cytometry, and H&E staining.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002050","title":"Gene expression and chromatin accessibility profiling of human PBMC samples","description":"This study investigates gene expression and chromatin accessibility responses in experimentally stimulated human PBMC samples. Samples from multiple donors were collected or analyzed at Day 0 and Day 6 under control and stimulation conditions. Pooled gene-expression and ATAC-seq libraries were sequenced on an Illumina NovaSeq platform. The gene-expression and chromatin-accessibility data originate from the same study and biological sample collection.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002051","title":"Longitudinal bulk T cell receptor sequencing of pre-diagnosis SUMMIT blood samples","description":"This study contains controlled-access bulk T cell receptor sequencing data from longitudinal peripheral blood samples collected from participants in the SUMMIT study before lung cancer diagnosis. Samples were collected at defined pre-diagnosis timepoints (Y0, 3M and Y1, where available) and were used to investigate longitudinal changes in circulating T-cell clonotypes and TCR repertoire composition preceding diagnosis. Only the pre-diagnosis SUMMIT samples are included in this study; diagnosis-timepoint samples used in the paper are deposited separately as part of the ASCENT dataset.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002052","title":"Whole-exome sequencing (WES) libraries of plasmablastic lymphoma","description":"Plasmablastic lymphoma (PBL) is an aggressive B-cell lymphoma associated with Epstein-Barr virus (EBV), MYC rearrangements (MYC+), and immunodeficiency. Here we generated whole exome sequencing (WES), whole genome sequencing, and RNA-seq for 48, 5, and 38 tumors, respectively. Including data from published studies (PMID: 33225311, 33951889, 34465776, 34714908), we augmented our study size to a total of 174 PBL exomes and genomes, and 59 transcriptomes.\r\nSeeking biologically distinct subgroups, we stratified tumors using the combination of EBV expression and MYC rearrangement status (i.e. EBV+/MYC+, EBV+/MYC-, EBV-/MYC+, EBV-/MYC-), revealing distinct mutational profiles and a subgroup (EBV-/MYC+) with significantly poorer outcomes. Together, these results suggest that EBV and MYC status can distinguish biologically distinct and therapeutically actionable subgroups within PBL.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002053","title":"Bulk RNA-seq libraries of plasmablastic lymphoma","description":"Plasmablastic lymphoma (PBL) is an aggressive B-cell lymphoma associated with Epstein-Barr virus (EBV), MYC rearrangements (MYC+), and immunodeficiency. Here we generated whole exome sequencing (WES), whole genome sequencing, and RNA-seq for 48, 5, and 38 tumors, respectively. Including data from published studies (PMID: 33225311, 33951889, 34465776, 34714908), we augmented our study size to a total of 174 PBL exomes and genomes, and 59 transcriptomes.\r\nSeeking biologically distinct subgroups, we stratified tumors using the combination of EBV expression and MYC rearrangement status (i.e. EBV+/MYC+, EBV+/MYC-, EBV-/MYC+, EBV-/MYC-), revealing distinct mutational profiles and a subgroup (EBV-/MYC+) with significantly poorer outcomes. Together, these results suggest that EBV and MYC status can distinguish biologically distinct and therapeutically actionable subgroups within PBL.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002054","title":"Whole-genome sequencing (WGS) libraries of plasmablastic lymphoma","description":"Plasmablastic lymphoma (PBL) is an aggressive B-cell lymphoma associated with Epstein-Barr virus (EBV), MYC rearrangements (MYC+), and immunodeficiency. Here we generated whole exome sequencing (WES), whole genome sequencing, and RNA-seq for 48, 5, and 38 tumors, respectively. Including data from published studies (PMID: 33225311, 33951889, 34465776, 34714908), we augmented our study size to a total of 174 PBL exomes and genomes, and 59 transcriptomes.\r\nSeeking biologically distinct subgroups, we stratified tumors using the combination of EBV expression and MYC rearrangement status (i.e. EBV+/MYC+, EBV+/MYC-, EBV-/MYC+, EBV-/MYC-), revealing distinct mutational profiles and a subgroup (EBV-/MYC+) with significantly poorer outcomes. Together, these results suggest that EBV and MYC status can distinguish biologically distinct and therapeutically actionable subgroups within PBL.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002055","title":"Cell-free DNA Whole Genome Sequencing for Non-Invasive Minimal Residual Disease Detection in Multiple Myeloma","description":"Minimal residual disease (MRD) monitoring in multiple myeloma (MM) relies on invasive bone marrow (BM) biopsies, which often yield insufficient tumor material. We performed whole genome sequencing of cell-free DNA from 163 plasma samples from 51 patients to develop a non-invasive MRD classifier. BM WGS identified a median of 2,502 clonal mutations, enabling cfDNA tracking at levels comparable to BM-based MRD testing. The cfDNA classifier achieved a mean AUC of 0.86 against multiparameter flow cytometry and targeted immunoglobulin sequencing (clonoSEQ), and MRD negativity after one year of maintenance was strongly associated with two-year relapse-free survival probability (Hazard Ratio = 24), with cfDNA changes preceding clinical progression by a median of 12.6 months. To establish a BM-agnostic mode, a plasma-only classifier trained on baseline cfDNA established a mean AUC of 0.79 compared to BM clinical testing and stratified relapse risk (HR = 4.18), enabling MRD detection in patients with suboptimal BM samples. Longitudinal cfDNA profiles detected subclonal evolution in half of profiled patients. Cell-free DNA whole genome sequencing provides a sensitive, scalable, and clinically informative platform for non-invasive MRD monitoring in MM.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-14T13:03:43.262427+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002056","title":"Clinical and Genomic Characterization of Brazilian HER2-Positive Breast Cancer","description":"The objective of this study was to characterize the clinical profile, genomic ancestry, germline predisposition, and somatic alterations of Brazilian women with locally advanced HER2-positive BC treated with neoadjuvant chemotherapy plus trastuzumab and to evaluate their association with pCR.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002057","title":"Whole-exome and RNA-seq sequencing of HCC of metastatic and de novo origin","description":"Multifocal hepatocellular carcinoma (mfHCC) arises via intrahepatic metastasis (IM) or multicentric occurrence (MO), We performed whole-exome and RNA-sequencing of 76 tumor biopsies from 22 HCC patients to determine their evolutionary origins. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-02T14:59:12.527757+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002058","title":"Investigating PBMC immune profiles and cellular state alterations in latent tuberculosis infection by scRNA-seq","description":"Latent tuberculosis infection (LTBI) represents a state of persistent immune control against Mycobacterium tuberculosis without active clinical disease. This study aims to characterize the immune landscape of LTBI at baseline conditions compared to healthy controls, evaluating shifts in cellular composition and underlying cell-state transitions. PBMC samples from six LTBI donors and one healthy control were pooled using a sample-multiplexing approach prior to single-cell RNA sequencing. Cell barcodes were subsequently assigned to individual donors through computational SNP-based demultiplexing, providing high-resolution insights into host systemic immunity in latent infection.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002059","title":"TCRSeq data from ASTEROID trial","description":"To characterize treatment-associated changes in the T-cell receptor (TCR) clonotype repertoire, TCR sequencing was performed on RNA isolated from paired tumor specimens and serial peripheral blood mononuclear cell (PBMC) samples using the FUME-TCRseq platform (PMID: 38479434).","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[38479434],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002060","title":"TIM3 blockade with hypomethylating therapy restores NK and cytotoxic CD4+ T cell activity in patients with AML or MDS","description":"Acute myeloid leukemia (AML) remains a therapeutic challenge, requiring novel combination strategies to improve patient outcomes. This study investigates the cellular and molecular dynamics of bone marrow microenvironments in patients receiving combination therapy with anti-TIM3 and decitabine within a phase Ib clinical trial (NCT03066648). By analyzing longitudinal samples, the project aims to characterize treatment response, resistance mechanisms, and microenvironmental shifts at single-cell resolution. The resulting insights provide a comprehensive framework for evaluating checkpoint inhibition combined with hypomethylating agent in AML and MDS.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-08-28T15:00:38.226113+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002061","title":"A targetable dependency on nonsense-mediated decay for cellular homeostasis and immune control in small cell lung cancer","description":"Small cell lung cancer (SCLC) is one of the most aggressive malignancies, characterized by rapid metastatic dissemination and poor overall survival. Despite harboring one of the highest tumor mutational burden (TMB), expectedly resulting in immunogenic neoantigens, patients with SCLC remain largely refractory to immunotherapy. We found abundant frameshift mutations in SCLC, regarded as highly immunogenic, counterbalanced by a hyperactive nonsense-mediated decay (NMD) pathway, responsible for frameshift-mRNA degradation. NMD activity correlated with tumor mutational burden (TMB) across cancers, suggesting that SCLC and other TMB-high cancers may depend on NMD to limit the accumulation of mutation-derived byproducts in order to maintain cellular homeostasis and evade immune recognition. In TMB-high SCLC models, inhibition of NMD impaired cell proliferation and induced ER stress-dependent apoptosis due to the accumulation of misfolded proteins. Genetic and pharmacological NMD inhibition in vivo effectively controlled TMB-high tumor growth without overt toxicity. By integrating genome and transcriptome sequencing with MHC-I immunopeptidomics and functional in vitro and in vivo assays, we identified that NMD inhibition boosted neoantigen expression and presentation by tumor cells and increased T cell recognition, thus enhancing overall tumor immunogenicity and further improving immunotherapy efficacy in vivo. Our work shows that SCLC – as a TMB-high cancer – relies on NMD for survival and immune escape, uncovering a novel TMB-dependent tractable vulnerability for this devastating disease.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-09T11:45:31.901739+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002062","title":"PEGASUS cohort transcriptomic profiling","description":"This study characterizes the transcriptomic landscape of FFPE tumor tissue samples from the PEGASUS colorectal cancer cohort using Digital mRNA-seq (NEGEDIA, Next Generation Diagnostic srl). Libraries were sequenced single-end on an Illumina NovaSeq 6000.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-20T12:50:28.709573+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002063","title":"Borneo HG Lifestyle Transition Multiomics Study [WGS]","description":"The study explores the multi-omics dimension of lifestyle transition gradients in three populations in Indonesian Borneo. The study involves the Punan Batu community (largely mobile hunter-gatherers), Punan Tubu (resettled/transitioned hunter-gatherers), and Lundayeh (agriculturalists). The study generated Whole Genome Sequences (mean coverage ~20x) from the three communities involved.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002064","title":"Borneo HG Lifestyle Transition Multiomics Study [Whole Transcriptome]","description":"The study explores the multi-omics dimension of lifestyle transition gradients in three populations in Indonesian Borneo. The study involves the Punan Batu community (largely mobile hunter-gatherers), Punan Tubu (resettled/transitioned hunter-gatherers), and Lundayeh (agriculturalists). The study generated Whole Transcriptomes (60M reads) from the three communities involved.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002065","title":"A single-cell atlas of large B cell lymphomas reveals distinct malignant archetypes predictive of clinical outcomes","description":"Large B cell lymphomas (LBCLs) exhibit significant heterogeneity which leads to disparate treatment response, with up to 40% of patients developing refractory disease or relapsing within the first two years. To understand the cellular and molecular basis of this heterogeneity, we performed single-cell RNA-seq, BCR-seq, and TCR-seq on LBCL tumor biopsies, generating an atlas of 63 LBCL cases, mostly classified as diffuse LBCL, not otherwise specified (DLBCL NOS). We identified five conserved transcriptional archetypes of malignant B cells that co-occur within individual tumors, with varying proportions across patients. Notably, high abundance of Archetype 4, characterized by memory B cell features and quiescence markers, correlated with poor event-free survival following standard immunochemotherapy, a finding which was validated in independent cohorts through deconvolution of bulk RNA-seq data. Our study provides a novel framework for patient stratification based on the quantification of malignant cellular states, with implications for precision therapy of LBCLs. Single-cell RNA-seq, BCR-seq and TCR-seq data (10x Genomics 5') for the cohort are deposited in this study.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-23T17:10:11.503704+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002066","title":"Clonal landscape of human nephrons","description":"This study investigates somatic mosaicism in human normal kidneys. By combining laser-capture microdissection of distinct nephron segments with high-throughput sequencing, we evaluated segment-specific mutational burdens, clonal expansion, renal cancer-related driver mutations, and copy number abnormalities across different age groups. Furthermore, single-nucleus RNA sequencing  was performed to examine transcriptomic changes and functional consequences associated with these alterations.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002067","title":"PBMCs Bellini TNBC anti-PD1 monotherapy","description":"Immune checkpoint blockade (ICB) combined with chemotherapy (CT) has improved outcome in high-risk early-stage triple-negative breast cancer (TNBC); yet it is unclear which patients benefit from the addition of ICB beyond chemotherapy alone. We profiled 67 serial tumor and 175 blood samples obtained before and during anti-PD1 treatment across 3 breast cancer trials using single-cell transcriptomic and T cell receptor (TCR) sequencing. Early intratumoral T cell expansion emerged as a consistent hallmark of clinical benefit. This expansion was reflected in increased TCR sharing between tumor and blood after treatment initiation, with shared blood T cells displaying immune-activated programs and their tumor counterparts enriched for expanding clonotypes, suggesting blood-to-tumor trafficking of activated T cells. In TNBC treated with anti-PD1+CT, T cell expansion distinguished an immune-driven response from a chemotherapy-dominant route to pathological complete response (pCR). To enable baseline patient stratification, we derived a 15-gene tumor signature predictive of T cell expansion, which associated with response in independent breast cancer cohorts and with improved survival across ICB-treated cancer types. Our data establish T cell expansion as an early marker of sustained ICB response and could allow stratification of patients likely to benefit from the addition of ICB to chemotherapy. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[39284953],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002068","title":"Early establishment of the naïve B-cell receptor repertoire with gradual antigen-experienced maturation after pediatric hematopoietic stem cell transplantation","description":"Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for diverse inherited and acquired immuno-hematological disorders. While quantitative B-cell recovery is well characterized, qualitative reconstitution of the B-cell receptor (BCR) repertoire, particularly in pediatric patients, remains incompletely defined. We delineated longitudinal reconstitution of naïve and antigen-experienced immunoglobulin heavy chain (IGH) repertoires during the first two years after pediatric HSCT. Peripheral blood mononuclear cells from 10 pediatric patients were analyzed at 3, 6, 12, and 24 months post-HSCT and compared with age-matched healthy donors. High-throughput sequencing of IGH transcripts was performed to assess V(D)J gene usage, repertoire diversity, junctional characteristics, somatic hypermutation (SHM), and clonal architecture across naïve and antigen-experienced compartments.\r\nThe naïve IGHM repertoire demonstrated broad, unbiased IGHV, IGHD, and IGHJ gene usage as early as 3 months post-HSCT, with diversity and junctional features comparable to controls. In contrast, antigen-experienced repertoires (IGHG and IGHA) showed reduced SHM frequencies and diminished N-nucleotide insertions during the first year, normalizing by 24 months. Despite delayed SHM accumulation, targeting of activation-induced cytidine deaminase and polymerase η motifs and replacement-to-silent mutation ratios were preserved, indicating intact molecular affinity maturation. Clonal expansions were detectable in class-switched compartments but did not compromise overall repertoire diversity.\r\nThese findings indicate early establishment of a diverse naïve IGH repertoire after pediatric HSCT, followed by gradual maturation of antigen-experienced repertoires, resembling key features of physiological B-cell development.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-23T17:08:46.670608+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002069","title":"Utility of whole exome sequencing for genomic newborn screening in India","description":"This study evaluates the use of genomic newborn screening to identify clinically relevant genetic variants in critically ill neonates. The project aims to investigate the potential of whole-exome sequencing (WES) for the early identification of rare genetic disorders. The study seeks to improve early diagnosis and support timely clinical management of neonates with suspected genetic conditions.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-07T14:37:38.756728+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002070","title":"Epigenetic Heterogeneity in Breast Tumors with Implications for Disease Diagnosis and Monitoring","description":"This study investigates epigenetic heterogeneity in human breast cancer using complementary single-cell and bulk epigenomic approaches. Human breast tumor samples were profiled using whole-genome bisulfite sequencing, enzyme-mediated methylation sequencing of sorted tumor-cell populations, single-nucleus CUT&Tag, and single-cell RNA and chromatin-accessibility multiome profiling. These data were used to characterize recurrent epigenetic cell states and intra-tumor heterogeneity in breast cancer.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-17T17:02:36.247927+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002071","title":"Genomic and Transcriptomic Topography of Subclonal Evolution in Intrahepatic Cholangiocarcinoma","description":"The rising incidence and poor outcomes of intrahepatic cholangiocarcinoma (iCCA) are partly attributable to an incomplete understanding of its molecular heterogeneity.  Intratumor heterogeneity (ITH) in other cancers is associated with  the emergence of increasingly aggressive clones but is less-well characterized in iCCA.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002072","title":"Distinct molecular profiles characterize the spontaneous growth rate of IDHmt low-grade astrocytomas and oligodendrogliomas","description":"The life expectancy of patients with diffuse IDH-mutant low-grade gliomas (IDHmt LGG) ranges from 5 to over 20 years. Tumor behavior, including spontaneous growth rate, varies even within homogeneously classified subtypes of oligodendroglioma and astrocytoma. Risk-adjusted treatment strategies are needed to avoid therapy-related toxicities without compromising outcome. The spontaneous tumor volume growth rate (TVGR) serves as a prognostic marker and predicts response to therapy. Accurate prediction of TVGR through biomarkers would enable improved evidence-based risk management. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[41460180],"external_links":null,"is_released":true,"released_date":"2026-09-28T16:52:30.548182+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002073","title":"Long-read methylation profiling in small intestinal neuroendocrine tumors","description":"This study represents an Oxford Nanopore long-read whole-genome sequencing resource for investigating the genomic and epigenomic characteristics of small intestinal neuroendocrine tumors (SI-NETs). The study contains data from 24 high-molecular-weight DNA samples collected from 12 patients. Each patient contributed one primary tumor sample and either a matched peripheral blood sample or a matched normal tissue sample. In total, the study comprises 12 primary tumor samples and 12 patient-matched normal samples.\r\nThe samples were sequenced on Oxford Nanopore PromethION R10.4.1 flow cells, using one flow cell per sample. Basecalling was performed with Dorado in super-accurate mode with a minimum quality score of Q ≥10. The data are provided as 24 unmapped BAM (uBAM) files containing 5-methylcytosine (5mC) modified-base annotations, with one file generated for each sequenced sample. This resource enables the characterization of native DNA methylation patterns and genome-wide genomic alterations, including single-nucleotide variants, insertions and deletions, structural variants, and copy-number alterations, in SI-NETs and can support future studies of SI-NET tumor biology.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002074","title":"Whole-genome sequences of the Korean population generated using long-read technologies","description":"We performed long-read whole-genome sequencing of 19 Korean individuals to construct a Korean pangenome reference. Genomic DNA was extracted from peripheral blood of 16 individuals and from lymphoblastoid cell lines (LCLs) of 3 individuals, and DNA quality and quantity were assessed prior to library preparation. Twelve individuals underwent HiFi long-read sequencing on the PacBio Revio platform (mean raw depth ~26×), and seven individuals underwent long-read sequencing on the Oxford Nanopore PromethION platform (mean raw depth ~24×). Two of the Revio-sequenced individuals (KOR-003 and KOR-004) additionally underwent Hi-C sequencing (Dovetail Omni-C, Illumina NovaSeq X) to support haplotype-resolved, chromosome-scale assembly, and KOR-003 was also sequenced on the PromethION platform. Samples are identified as KOR-003 to KOR-021 (recorded as KOR_003 to KOR_021 in the sample aliases). Whole-genome sequences of three further Korean individuals, generated previously using the PacBio Sequel II system, are available in the European Genome-phenome Archive (EGA) under study accession EGAS50000000375.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-18T17:07:07.134036+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002075","title":"Rep2Eps BKPyV-specific LIBRA-seq","description":"Objective : Compare the BKPyV-specific B-cell repertoire between kidney transplant recipients who controlle BK polyomavirus DNAemia, versus those who did not\r\nMethodology : LIBRA-seq using whole capsids of the 4 BKPyV genotypes\r\nDatasets : BCR vdj ; 5'GEx ; Cell-surface hashtag antibody ; BEAM (LIBRA-seq probes)","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002076","title":"KHKi in MASLD","description":"muscle biopsy RNA sequenceing data of 12 participants treated with a KHK inhibitor and placebo for 6 weeks in a cross-over design clinical trial.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-02T17:20:22.827246+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002077","title":"Tertiary lymphoid structures boost T cell reinvigoration upon immunotherapy","description":"Tertiary lymphoid structures (TLSs) have been associated with immunotherapy response, but how they modulate T cell-driven antitumour immunity is unknown. By integrating spatially resolved T cell receptor (TCR) repertoire analysis, single-cell transcriptional profiling, and ex vivo TLS modelling, we interrogated how TLSs shape T cell clonality, phenotype, and functional responsiveness to PD1 blockade. We found that T cell activation pathways were enriched in TLSs, indicating they may serve as hotspots for T cell activity. TLSs and tumour bed regions showed substantial overlap in expanded T cell clones, suggesting that T cell activity in TLSs is not driven by distinct repertoires. These shared clones displayed dysfunctional states, indicative of tumour reactivity. Spatial transcriptomics revealed that T cells in TLSs enriched for precursor-dysfunctional states, while the tumour bed contained more late dysfunctional and effector cells. Using patient-derived tumour fragments to model distinct tumour regions ex vivo, we observed profound immune activity in TLSs following treatment with anti-PD1, with TLSs, with induction of proinflammatory cytokine and chemokine secretion, and increased expression of T cell activation genes in various T cell subsets. Our data reveal that TLSs enhance immunotherapy responses by acting as reservoirs preserving tumour-reactive T cell functionality and by directly boosting T cell responses upon checkpoint blockade.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002078","title":"Single-cell analysis of clonal evolution and tissue architecture in B-cell lymphomas","description":"Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are B-cell lymphomas characterized by substantial molecular and clinical heterogeneity. In this study, we aimed to define clonal architecture, the temporal order of genetic alterations, and intratumoral heterogeneity in DLBCL and FL using single-cell DNA sequencing with matched cell-surface protein profiling. Tapestri single-cell DNA and surface protein profiling was performed on 31 samples from 29 patients, with whole-exome sequencing used for validation in a subset of cases. In addition, Visium HD spatial transcriptomic profiling was performed in selected FL cases to investigate the relationship between genetic and clonal evolution and tissue architecture.","abstract":null,"study_type":"Synthetic Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002079","title":"Validating ctDNA Observation vs. Routine Investigations (VICTORI) Study ","description":"VICTORI is an observational, prospective study exploring the use of the NeXT Personal ctDNA assay in exploring minimal residual disease (MRD) in patients with colorectal cancer following curative intent surgery. Whole-genome informed panels of ~1,800 variants were created for patients, and were used to interrogate plasma samples collected at baseline, and weeks 2, 4, 6 and 8 post-surgery as well as every 3 months on surveillance. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002080","title":"Single cell atlas of follicular lymphoma","description":"We performed single-nucleus RNA sequencing (snRNA-seq) and single-cell spatial transcriptomics (ST) across a large cohort of FL and control samples to characterize the cellular composition and spatial organization of the FL microenvironment. In total, snRNA-seq was performed on 171 samples (FL, n = 167; control, n = 15) and spatial transcriptomics on 386 samples (FL, n = 365; control, n = 21). This study provides a comprehensive single-cell and spatial resource for investigating FL biology, microenvironmental organization, and their associations with clinical features.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002081","title":"Raw sequencing data from a phase 2 trial of dasatinib in patients with relapsed/refractory nodal T-follicular helper cell lymphoma","description":"De-identified raw sequencing data, including scRNA-seq data from peripheral blood samples, snRNA-seq data from tumor tissues, and bulk RNA-seq data from tumor tissues.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-03T08:42:14.289337+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002082","title":"Rhabdoid tumors WGS from Sánchez-Guixé et al. \"Variable latency between the founder genetic event and rhabdoid tumor expansion\" 2026","description":"Whole Genome Sequencing from tumors and normal blood samples from 16 cases diagnosed with rhabdoid tumors in SJD hospital and 1 case from Princess Maxima Center (PMC) (total 17 cases)","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[42427603],"external_links":null,"is_released":true,"released_date":"2026-09-16T10:51:56.338416+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002083","title":"Matrix compaction drives inflammatory fibroblast fate through HMGA1-mediated epigenetic reprogramming ","description":"Bulk RNA-sequencing and single-nucleus multiome profiling of human gastric fibroblasts under matrix compaction","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002084","title":"Single-cell RNA sequencing of in vitro stimulated peripheral blood mononuclear cells (4 healthy donors; 4 conditions; 2 incubation time points)","description":"This study profiled the transcriptome of in vitro stimulated healthy peripheral blood mononuclear cells (PBMCs) at asingle-cell level. Four healthy control individuals, four stimulatory conditions and two incubation time points were included in this study, resulting in a total of six multiplexed single-cell samples (CEV017-CEV022), each containing up to seven samples, which were demultiplexed based on nuclei hashing and SNP-identification. In-depth information of the multiplexed samples is present in Supplementary Table S3 of the manuscript. The samples were processed using the Chromium Next GEM Single Cell 5' Reagent Kits v2 (10X Genomics) and sequenced on the Illumina Novaseq 6000 platform using the Novaseq 6000 S2 Reagent Kit v1.5 (100 cycles). Preprocessing and downstream analysis was performed using CellRanger and Seurat.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002085","title":"Polynesian Founder Effects","description":"Founder effects can lead to strong, population-specific allele frequency differentiation, including autosomal recessive conditions. Their characterization in European-descent groups such as the Finnish and Amish has resulted in actionable genetic tests for each. We show that Polynesians experienced an order-of-magnitude stronger cumulative founder effects during their settlement of Eastern Polynesia. Using whole genome sequences spanning Polynesia, we show that two of the most bottlenecked populations are Hawaiʻi and Easter Island (Rapa Nui), and that these two most closely genetically related yet geographically distant islands were likely settled by the same ultra-voyagers with earlier ancestral roots in Mangareva. We identify clinical genetic variation generated by this sequence of successive oceanic founder events, including a loss-of-function FAN1 mutation common in Eastern Polynesia (>1%) but entirely absent from gnomAD.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002086","title":"Phenomic and multiomic characterisation of microsatellite-stable colorectal cancer reveals novel biology and targets of vulnerability (COLOSSUS project): metastatic (m)CRC cohort","description":"This dataset contains bulk RNA sequencing samples (n = 111) and low-coverage whole-genome sequencing (n = 113). Primary tumour samples were retrospectively obtained from colorectal cancer patients who developed metastatic colorectal cancer (stage 4), for whom tissue from the primary tumour was available.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-16T10:57:57.172684+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002087","title":"Phenomic and multiomic characterisation of microsatellite-stable colorectal cancer reveals novel biology and targets of vulnerability (COLOSSUS project): snRNASeq cohort","description":"This dataset contains single-nuclei RNA-sequencing (n = 18) samples. Primary tumour samples were obtained from a) colorectal cancer patients with stage 2 / 3 disease and b) colorectal cancer patients who developed metastatic colorectal cancer (stage 4), for whom tissue from the primary tumour was available.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-16T10:57:51.26572+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002088","title":"Phenomic and multiomic characterisation of microsatellite-stable colorectal cancer reveals novel biology and targets of vulnerability (COLOSSUS project): Stage (St) 2/3 CRC cohort","description":"This dataset contains bulk RNA sequencing (n = 184), low-coverage whole-genome sequencing (n = 182) and whole-exome sequencing (n = 88) data. Primary tumour samples were obtained from colorectal cancer patients with stage 2 / 3 disease. ","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-16T10:57:54.336681+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002089","title":"A novel syndromic immunodeficiency associated with mutation of rasGTPase-Activating Protein RASAL3","description":"In this study we describe a set of compound heterozygous variants in the RASAL3 gene, causing primary immunodeficiency associated with T cell lymphopenia, recurrent sinopulmonary infections, oral ulcers, skin lesions, persistent hematuria, and atopy. The patient also displayed neurological abnormalities, including developmental delay, seizures, and hypoalgesia. WES data from the proband (patient 1) is deposited.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-05T14:09:32.775724+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002090","title":"Advancing Neurological Liquid Biopsy via Six-Base Sequencing of Cerebrospinal Fluid Cell-Free DNA ","description":"Real-time molecular insights into the human brain are crucial for understanding neurological conditions and development of soluble biomarkers but challenged by the limited access to target tissue. Here we utilize 6-base sequencing to profile DNA modifications of cell-free DNA released from neural cells into cerebrospinal fluid. This strategy provides molecular, quantitative and qualitative insights into the ongoing neurodegenerative biology, which paves the way for liquid biopsy approaches to study neurological conditions.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002091","title":"Aberrant thymic architecture and enhanced interferon signaling in Down syndrome ","description":"It is well established that individuals with Down syndrome (DS) have an elevated risk of autoimmune disease, particularly celiac disease, type 1 diabetes, and autoimmune hypothyroidism. DS thymi are often characterized by alterations to thymic epithelial cells (TECs), thymocytes, and functional immune cell subsets resulting in diminution of the cortex, expansion of the medulla, and concurrent enlargement of highly keratinized Hassall’s corpuscles. Yet, how these structural and compositional changes to the thymus may contribute to the propensity for autoimmune disease in DS is still unclear. To better understand the relationship between thymic development and immune dysregulation in the context of DS, we created a cell atlas from single cell RNA-sequencing (scRNA-seq) and spatial transcriptomics of age-matched thymi from infants with and without DS. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-10T16:43:11.296127+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002092","title":"Inhibition of DGKα/ζ overcomes intratumoral T cell dysfunction through enhanced TCR signalling in human cancers resistant to PD-1 blockade ","description":"Immune checkpoint blockade (ICB) targeting the PD-1–PD-L1/2 axis can restore T cell receptor (TCR) signaling and reinvigorate CD8⁺ T cells in some tumors. However, many tumors remain unresponsive, suggesting additional inhibitory mechanisms. Diacylglycerol kinases (DGKs), particularly DGKα and DGKζ, act as intracellular checkpoints by metabolizing diacylglycerol (DAG), thereby dampening DAG dependent TCR signaling required for full T cell activation. Thus, inhibition of DGK may represent an attractive strategy to enhance T cell activation, particularly in tumors resistant to anti-PD-1 therapy. To test this, we treated patient-derived tumor fragments (PDTFs) ex vivo with a DGKα/ζ inhibitor (DGKi), alone or in combination with anti-PD-1. DGKi treatment induced robust activation of intratumoral T cells, as evidenced by increased cytokine and cytotoxic mediator production. Notably, DGKi was effective even in a large fraction of tumors unresponsive to anti-PD-1 monotherapy. Single-cell transcriptomic analysis revealed that DGKi induced a distinct activation program in CD8+ T cells, most pronounced in antigen-experienced, dysfunctional cells, with its combination with anti-PD-1 further engaging NF-κB linked effector programs. These effects were dependent on TCR signaling, underscoring the role of DGK as a critical intracellular brake on T cell activation. Our findings suggest that DGKs represent an additional checkpoint limiting T cell effector function and their inhibition can reinvigorate dysfunctional CD8⁺ T cells, potentially overcoming resistance to PD-1 blockade. Thus, targeting DGKα and/or DGKζ may represent a promising strategy to enhance antitumor immunity and improve the efficacy of current immunotherapies.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002093","title":"cfDNA multi-cancer study","description":"This study benchmarked 8 published tumor-naïve ctDNA quantification methods (cfNOMe, cfSort, MethAtlas, MIMESIS, SRFD-Bayes, UXM, ichorCNA, and Fragle), individually and in combination, across 3 cancer types and sequencing depths from 0.1x to 30x. Matched deep WGS and enzymatic methyl-sequencing (EM-seq) data were generated from plasma cell-free DNA of 150 patients with colorectal, lung, or breast cancer and 16 healthy volunteers. We assessed classification accuracy, tumor fraction concordance, and limits of detection and quantification by downsampling and in silico dilution of these data.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002094","title":"G4SCOPE identifies sequence features and epigenetic contexts of chromatin G-quadruplexes","description":"Cancer-associated epigenetic remodeling involves both DNA secondary structures and covalent cytosine modifications, yet predicting chromatin-constrained G-quadruplex (G4) folding remains challenging. Here, we develop G4SCOPE, a multi-task deep learning framework that predicts G4 occupancy and quantitative CUT&Tag signal directly from DNA sequence in isogenic human breast epithelial cells. Trained across wild-type, TP53-deficient, TP53/BRCA1-deficient and TP53/BRCA2-deficient backgrounds, the model integrates convolutional motif learning with transformer-based self-attention to capture local motifs and broader contextual sequence features without auxiliary epigenomic inputs. It distinguishes chromatin-associated G4s from GC-matched loci with in vitro G4-forming potential, captures quantitative variation in local CUT&Tag signal, and performs consistently across the four breast epithelial genotypes. Independent application in K562 cells further supports the portability of the framework to a distinct cellular context. Model-derived G4 representations also separate loci with distinct local 5-methylcytosine and 5-hydroxymethylcytosine profiles. Together, these results show that DNA sequence can predict chromatin G4 occupancy and quantitative CUT&Tag signal, and that the learned representations reflect differences in local cytosine-modification state.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-03T12:10:08.512015+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002095","title":"Phase I Clinical Trial of Allogeneic Cytomegalovirus-specific T Cells in Combination with Pembrolizumab for Recurrent Glioblastoma","description":"Glioblastoma (GBM) remains refractory to immunotherapy, in part due to its profoundly immunosuppressive tumour microenvironment. Tumour-infiltrating cytomegalovirus (CMV)-specific T cells express elevated levels of programmed cell death protein-1 (PD-1), suggesting that adoptive T-cell therapy may be limited by checkpoint-mediated dysfunction. We therefore evaluated the safety and immunological activity of CYT-101, an allogeneic CMV-specific T-cell therapy, administered in combination with pembrolizumab. This study included single cell RNA and TCR sequencing to provide an initial phenotype of the four products used as immunotherapies. ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002096","title":"Transcriptome analyses of rhabdoid tumors and their microenvironment by bulk and single-cell RNAseq","description":"Rhabdoid tumors (RTs) are aggressive pediatric malignancies with poor prognosis and limited immunotherapy options. The aim of this study is to investigate the therapeutic potential of combined PD-L1 (Programmed cell death ligand 1) and TIGIT (T cell immunoreceptor with Ig and ITIM domains) immune checkpoint blockade in RTs. To characterize the expression patterns of ligands and receptors from these immune checkpoint families, bulk and single-cell RNA sequencing across multiple RT subtypes were generated.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002097","title":"Sequencing data from fragmentation-derived artificial cfDNA reference standards","description":"Panel sequencing data generated from artificial cfDNA reference standards and matched white blood cell DNA fragmented using sonication, MNase, or dsDNase. The dataset includes panel sequencing data used to compare fragmentation-derived DNA reference standards with plasma cfDNA.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002098","title":"ENLs Organoid Interactions Upon ENL CDCA Stimulation and Organoid Tofacinitib Treatment","description":"Primary bile acid accumulation, specifically chenodeoxycholic acid (CDCA), is a hallmark of Crohn’s Disease (CD) ileal dysbiosis. However, how this metabolic shift impacts the enteric nervous system (ENS) to drive mucosal pathology remains poorly defined.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002099","title":"Treatment of iPSC-ENLs from Healthy Controls and IBD Lines with PBS or 150µM CDCA","description":"Analysis of 24h treatment with CDCA 150uM of iPSC-ENLs from Healthy and IBD lines after day 70 of differentiation. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002100","title":"Co-culture of ENL and ileum organoids with 300uM CDCA and 100ng/mL IFNg treatment","description":"Analysis of ENLs co cultured with ileum organoids stimulated or not with IFNg 100ng/mL and individual analysis of ENLs from heatlhy and IBD lines treated with CDCA 300uM. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002101","title":"Molecular characterization of pathogenic AHCY variants in AHCY deficiency","description":"This study investigates the molecular basis of S-adenosylhomocysteine hydrolase (AHCY) deficiency, a rare inherited metabolic disorder. Clinical exome sequencing of an affected patient identified two previously uncharacterized compound-heterozygous variants in the AHCY gene. The study investigates the molecular and functional consequences of these variants and their contribution to AHCY deficiency, with the aim of improving our understanding of disease mechanisms and potential therapeutic strategies.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002102","title":"Deciphering immune interactions between iPSC-derived enteric neural lineages and 3D intestinal epithelial organoids in mucosal inflammation","description":"Comparison between CDCA treated healthy lines and Bax/Bak knockdown lines constructed via Lentiviral transduction.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002103","title":"IMMUcan DEDICATION NSCLC3 cohort","description":"The goal of IMMUcan is to understand how the immune system interacts with tumors and how therapeutic interventions influence this interaction. This cohort focuses on research into the treatment of patients with non-small cell lung cancer with the immunotherapy drug pembrolizumab. Research is being done into whether this drug can be given in a lower dosage and more individually tailored. Dedication-1 study (NVALT 30) (Non-small cell lung cancer) Comprehensive profiling data are integrated with longitudinally collected clinical information. Cellular profiling of the same tumor samples was performed using multiplex immunofluorescence imaging, imaging mass cytometry, and H&E staining.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002104","title":"Clinical data of breast cancer patients from EuCanImage - Breast cancer MMG (Use case 6&8) ","description":"This study is part of EuCanImage project. It contains the standardized clinical information following FHIR model. The data was collected together with MMG of patients diagnosed with breast cancer and controls. This project focuses on AI-driven analysis of digital mammograms to address two key challenges in breast cancer diagnostics. The goal is to automatically classify the molecular subtypes of invasive ductal carcinoma and differentiate benign from malignant lesions across both screening and clinical settings. The study leverages a multi-center European dataset of full-field digital mammograms collected within the EuCanImage federated platform.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002105","title":"Clinical data of breast cancer patients from EuCanImage - Breast cancer MRI (Use case 7)","description":"This study is part of EuCanImage project. It contains the standardized clinical information following FHIR model. The data was collected together with  MRI of patients diagnosed with breast cancer","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002106","title":"Clinical data of rectal cancer patients from EuCanImage (Use case 4&5)","description":"This study is part of EuCanImage project. It contains the standardized clinical information following FHIR model. The data was collected together with MRI of patients diagnosed with rectal cancer.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002107","title":"Clinical data of colorectal liver metastasis (CRLM) patients from EuCanImage (Use case 3)","description":"This study is part of EuCanImage project. It contains the standardized clinical information following FHIR model. The data was collected together with CT of patients diagnosed with colorectal liver metastasis (CRLM) and controls.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002108","title":"Clinical data of Hepatocellular carcinoma patients from EuCanImage (Use case 1)","description":"This study is part of EuCanImage project. It contains the standardized clinical information following FHIR model. The data was collected together with MRI of patients diagnosed with liver cancer (HCC) and controls (non-HCC)","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":[{"url": "https://xnat.health-ri.nl/data/projects/euc_gumed_uc1", "name": "EuroBioimaging", "label": "EuCanImage_GUMED_UC1"}, {"url": "https://xnat.health-ri.nl/data/projects/euc_gumed_uc1", "name": "EuroBioimaging", "label": "EuCanImage_GUMED_UC1"}, {"url": "https://xnat.health-ri.nl/data/projects/euc_gumed_uc1", "name": "EuroBioimaging", "label": "EuCanImage_GUMED_UC1"}],"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002109","title":"Ongoing chromosomal instability in hTERT-RPE1 TP53/BRCA1/BRCA2 models","description":"Single-cell whole-genome sequencing of hTERT-RPE1 derived clones carrying TP53, BRCA1 and BRCA2 lesions, profiled across increasing numbers of doubling times and after drug treatment, to characterise ongoing chromosomal instability. Libraries were prepared either by automated direct library preparation (aDLP+, no whole-genome amplification) or by PicoPlex whole-genome amplification, and sequenced on the Illumina NovaSeq X. One library, and therefore one run, per individual cell.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002110","title":"Direct identification of de novo mobile element insertions from single molecule sequencing of human sperm","description":"Mobile element insertions (MEIs) are a significant source of human genetic variation, yet the rates and properties of de novo MEIs are poorly characterized due to technical limitations in sequencing technology. Here, we directly sequenced individual gametes from sperm samples of 19 donors (aged 27-62) using highly accurate PacBio long-read sequencing to identify de novo retrotransposition events without familial inference. We developed a “self-alignment” strategy using personalized genome assemblies that enables high-precision, single-read detection of de novo MEIs. Using this method, we identified 43 de novo Alu insertions, revealing >9-fold variation in Alu retrotransposition rates between individuals (ranging from 0 to 0.148 insertions/gamete). We found a significant increase in Alu activity with paternal age, yielding a 4.67% increase in insertions per gamete per year of additional paternal age, representing a direct observation of age-associated increases in structural variant (SV) mutation rates. De novo Alu insertions predominantly represent evolutionarily young AluYa5 and AluYb8 subfamilies and bear characteristic molecular signatures of target-primed reverse transcription (TPRT). Our population-averaged rate of 4.52 insertions per 100 gametes aligns well with previous population genetic estimates, validating both direct observation and population approaches for estimating de novo MEI rates. These results establish direct gamete sequencing as a powerful method for characterizing germline mutation processes and reveal age as a significant determinant of de novo retrotransposition in the male germline.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-23T15:40:38.234747+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002111","title":"Minimally invasive monitoring of clonal evolution in HGSOC through integrated single cell and ctDNA analysis","description":"Circulating cell-free DNA (cfDNA) offers a minimally invasive lens into tumor evolution. However, the accurate quantification of clonal composition from cfDNA remains challenging. Existing methods for clone tracking using liquid biopsies are constrained by issues such as their reliance on bulk tissue references, incomplete representations of clonal architecture or limited breadth of mutation panels. To address these limitations, we developed cfClone, a Bayesian framework that integrates single-cell whole-genome sequencing (scWGS) derived clonal structures with cfDNA whole-genome sequencing (cfDNA-WGS) data to enable high-resolution tissue-informed clonal tracking. By jointly modeling local copy-number alterations and haplotype-specific signals via Bayesian model selection and Markov chain Monte Carlo (MCMC) sampling, the algorithm yields uncertainty-aware estimates of clonal prevalence and tumour fraction (TF). Applied to longitudinal clinical cohorts, cfClone can be used to reconstruct evolutionary trajectories and uncovers clonal selection driving therapeutic resistance, including the de novo detection of emergent clonal populations. We demonstrate that cfClone achieves accurate TF estimates and circulating tumor DNA (ctDNA) detection in malignancies with varying degrees of copy-number variant (CNV) burden using semi-synthetic data. We then compare to the state of the art scWGS informed panel based approach, and demonstrate cfClone provides comparable accuracy while allowing for the tracking of more clones and detection of novel clones. Finally, we show how cfClone can be used to quantitatively track clonal dynamics in response to treatment in high grade serous ovarian cancer.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002112","title":"CITE-seq of longitudinal PBMC samples from treatment-naive pwMS during ocrelizumab treatment","description":"Raw sequencing data from observational study using CITE-seq of longitudinal PBMC samples from treatment-naive pwMS during ocrelizumab treatment","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[42714077],"external_links":null,"is_released":true,"released_date":"2026-09-17T16:40:37.702129+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002113","title":"BioKey: T cell Trafficking and Expansion as Early Indicators of Sustained Clinical Response to Immune Checkpoint Blockade","description":"BioKey (NCT03197389) is a single-center, open-label, non-randomized window-of-opportunity study conducted at University Hospitals Leuven in female patients with non-metastatic, newly diagnosed primary invasive breast cancer (ER−/PR− or ER+). Patients in cohort A (n=27) were treatment-naïve and received a single dose of pembrolizumab (anti-PD1) 9±2 days before surgery. Patients in cohort B (n=11) received neoadjuvant chemotherapy for 20–24 weeks followed by a pembrolizumab boost before surgery. In both cohorts, a tumor biopsy and a paired peripheral blood sample were collected before anti-PD1 (baseline) and again at the time of surgery (after-boost), yielding paired samples from 38 patients in total. Single-cell data were generated to investigate T cell and B cell trafficking between tumor and blood during anti-PD1 treatment in early-stage breast cancer and complement the previously deposited BioKey tumor scRNA-seq and scTCR-seq dataset (EGAS00001004809).","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002114","title":"scRNAseq data from HNSCC biopsies before and after BA treatment","description":"Tumor biopsies from 6 head and neck small cell carcinoma (HNSCC) berfore and 3-weeks after bintrafusp-alfa (BA) treatment were analyzed using single-cell RNA sequencing.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-23T15:41:22.020235+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002115","title":"IMMUcan Nirvana NSCLC4 cohort","description":"The goal of IMMUcan is to understand how the immune system interacts with tumors and how therapeutic interventions influence this interaction. This cohort includes patients treated with PD-1 Inhibitor and Chemotherapy with Concurrent Irradiation at Varied Tumour Sites in Advanced Non-small Cell Lung Cancer from Nirvana (NCT03774732). Comprehensive profiling data are integrated with longitudinally collected clinical information. Cellular profiling of the same tumor samples was performed using multiplex immunofluorescence imaging, imaging mass cytometry, and H&E staining.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002116","title":"Autologous biopsy-derived co-culture platform for interrogation of intestinal epithelial-T cell crosstalk","description":"Interactions between intraepithelial lymphocytes (IELs) and the intestinal epithelium are central to mucosal homeostasis and disease. However, mechanistic in vitro studies describing their crosstalk in humans are limited by scarceness of primary material and insufficient knowledge about co-culture requirements. Here, we establish an autologous human duodenal IEL–organoid co-culture system encompassing expandable and bankable IEL and organoid protocols, with co-culture conditions that allow viability of both cell types.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002117","title":"Molecular Evolution and Resistance Mechanisms in a patient with NTRK3-rearranged Pancreatic Cancer","description":"Longitudinal circulating tumor DNA profiling via whole-genome and whole-exome sequencing monitored clonal evolution and dissected resistance mechanisms. A patient-derived organoid established at progression to larotrectinib partially recapitulated this complexity, providing a platform for pharmacotyping.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002118","title":"A new non-invasive prenatal paternity test based on double nucleotide polymorphisms abates sequencing uncertainties and improves sensitivity","description":"This study presents the development and validation of NEWPAT, a non-invasive prenatal paternity testing (NIPAT) approach based on fetal cell-free DNA (cfDNA) and Double Nucleotide Polymorphisms (DNPs). A targeted amplicon-based NGS panel including 979 markers was applied to genomic DNA, simulated maternal-fetal mixtures, and cfDNA samples from pregnant women and putative fathers. High-depth sequencing data were generated and analyzed to evaluate DNP performance for fetal DNA detection and paternity inference.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-01T10:00:37.873271+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002119","title":"Nanopore Sequencing for large deletion detection at the SRSF2 and DNMT3A locus","description":"This batch 1 of nanopore sequencing aims to detect the frequency of large deletions occuring at the on-target sites (SRSF2 or SF3B1) post-editing protocol with or without the addition of the molecule AZD7648.","abstract":null,"study_type":"Pooled Clone Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002120","title":"Nanopore sequencing for large deletion detection for the loci SRSF2 or DNMT3A - batch 2","description":"This study aims at assessing the large deletion frequency at the on-target cutting site for both loci SRSF2 or DNMT3A. This time, in addition to the molecule AZD7648, the PolQi has been added to reduce the frequency of large deletions.","abstract":null,"study_type":"Pooled Clone Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002121","title":"Strand-Seq","description":"This run covers the sequencing data from our Strand-Seq run. Single-cells have been sequenced to perform genome integrity analysis.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002122","title":"DNA Methylation Profiling of CSF-derived Cell-free DNA Distinguishes Germinoma from Non-germinomatous Germ Cell Tumors","description":"Intracranial germ cell tumors (IGCTs) are rare pediatric malignancies whose two principal subtypes — pure germinoma (GE) and non-germinomatous GCT (NGGCT) — require fundamentally different treatment regimens yet are difficult to distinguish non-invasively. Current serum and cerebrospinal fluid (CSF) biomarkers (AFP and β-hCG) lack the specificity and sensitivity needed for reliable subtype classification, and tissue biopsy is frequently precluded by deep midline tumor location. We performed enzymatic methyl-sequencing (EM-seq) on CSF-derived cell-free DNA (cfDNA) from a multi-institutional pediatric cohort of CSF samples. CSF cfDNA methylation profiling by EM-seq reliably discriminates GE from NGGCT, providing proof-of-concept for a minimally invasive, multi-dimensional liquid biopsy approach for IGCT subtype classification and molecular characterization.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002123","title":"Expressed IgG heavy-chain repertoires across IGHD-gene deletion genotypes","description":"This study examines whether a previously genotyped contiguous IGHD-gene deletion also changes the expressed IgG B-cell receptor repertoire. The same donor panel was previously sequenced as IgM. IgG libraries were generated for a subset of those donors so that homozygous-deletion, hemizygous, and non-deletion genotypes can be compared.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002124","title":"PPGL-Clonal evolution- RNAseq","description":"In this project, we aim to decipher the evolutionary trajectory from primary tumor to metastasis in pheochromocytoma and paraganglioma (PPGL), taking advantage of a paired primary-metastasis cohort.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002125","title":"PPGL-Clonal evolution- WES","description":"In this project, we aim to decipher the evolutionary trajectory from primary tumor to metastasis in pheochromocytoma and paraganglioma (PPGL), taking advantage of a paired primary-metastasis cohort.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002126","title":"Mutanome-guided immunopeptidomics of blood plasma for neoepitope detection in solid tumors is constrained by cfDNA variant calling sensitivity and MS detection limits","description":"Neoepitopes form the basis of tumor-specific immune responses, but their detection typically relies on invasive tissue biopsy. This study explored whether neoepitopes can be identified by mutanome- guided immunopeptidomics from blood plasma of cancer patients, using patient-specific mutanomes derived from cell-free DNA (cfDNA) or tumor genomic DNA (tgDNA). Whole-exome sequencing (WES) was performed on cfDNA, leukocyte DNA, and/or matched tumor tissue DNA from four cancer patients with brain metastases and four healthy donors.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002127","title":"Combination of a CCL21-gene modified dendritic cell vaccine and pembrolizumab induces immune responses in non-small cell lung cancer.","description":"In a phase I study of advanced NSCLC, intratumoral CCL21-DC vaccination combined with pembrolizumab was safe and resulted in stable disease in 36.8% of patients. Analysis of paired pre- and post-treatment tumor biopsy WES data, together with immune profiling of tumor biopsies and peripheral blood, revealed that disease stability was associated with increased T cell receptor diversity, enhanced CD4+ T cell infiltration, and expansion of novel CD4+ memory T cell clones. These findings suggest that CCL21-DC vaccination can stimulate antitumor immunity; however, its efficacy may be limited by insufficient tumor-specific T cell responses and persistent immunosuppressive signaling within the tumor microenvironment.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-16T10:48:41.26054+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002128","title":"Additional medulloblastoma cfDNA low-coverage WGS","description":"Low-coverage whole-genome sequencing of cell-free DNA from CSF samples collected across timepoints from medulloblastoma patients enrolled on SJYC07 and SJMB03. These data supplement the previously deposited cohort (EGAS00001005592).","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-29T16:48:41.713323+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002129","title":"Whole Exome Sequencing Study of Alport Syndrome","description":"This study investigates the genetic basis of Alport syndrome using whole exome sequencing. The study includes patients clinically investigated for Alport syndrome and aims to identify genetic variants associated with the disease. Whole exome sequencing data were analyzed to identify sequence variants in genes relevant to Alport syndrome and related hereditary kidney disorders. The resulting genetic variant data are deposited in the European Genome-phenome Archive (EGA) under controlled access to facilitate research while protecting participant privacy.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002130","title":"Essential tremor blood transcriptional variation and its association with clinical and neuroimaging phenotypes","description":"We performed whole-blood RNA-sequencing, brain MRI and clinical assessments for a cohort of essential tremor patients and controls. Both groups were cognitively unimpaired. The ET group had substantial motor and functional impairment with a mean disease duration of 7.8 years. In this project, we aimed to compare essential tremor and control groups on whole blood transcriptomic data, and within the essential tremor group, to test the correlation of transcriptional variation with key clinical and neuroimaging phenotyes.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-17T17:13:20.531943+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002131","title":"Closing the diagnostic gap in developmental disorders through comprehensive long-read sequencing","description":"As long-read sequencing technologies represent a promising approach to reduce the diagnostic gap in genetic testing for developmental disorders (DD), 28 patient-parents trios with unsolved DD following short read exome or genome sequencing have been sequenced using Oxford Nanopore.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002132","title":"NGS in FACSorted populations from AML patients","description":"FACS-enriched bone marrow cell populations from 22 AML patients were analyzed using a custom panel targeting 56 genes recurrently mutated in myeloid neoplasms. DNA was released from a median of 60,000 sorted cells by incubation with 2.5 μL proteinase K and 2 μL RNase A (Thermo Fisher Scientific) for 30 minutes at 37°C, purified using 2× AMPure XP beads (Beckman Coulter, Brea, CA), and stored in pH 8 elution buffer at −20°C. DNA quantity was measured using the Qubit dsDNA BR Assay on a Qubit 3.0 fluorometer (Thermo Fisher Scientific), and quality was assessed using the Genomic DNA ScreenTape assay on a 4200 TapeStation system (Agilent Technologies, Santa Clara, CA). Libraries were prepared from at least 20 ng of DNA according to the SOPHiA GENETICS protocol and sequenced on an Illumina MiSeq using 2 × 251-cycle paired-end reads. At least 95% of target bases achieved ≥1,000× coverage. FASTQ files were analyzed in SOPHiA DDM using the GRCh37/hg19 reference genome for alignment, variant calling, and annotation. Variants were retained when the variant allele frequency was ≥2%, coverage was ≥100 reads, and the alternate allele was supported on both strands. Synonymous, intronic, intergenic, 5′ untranslated-region, and recurrent panel-artifact calls were excluded. The remaining variants were classified according to Association for Molecular Pathology and American College of Medical Genetics and Genomics guidance using VarSome, ClinVar, COSMIC, and dbSNP. Only pathogenic or likely pathogenic variants were analyzed. All retained calls were visually confirmed in Integrative Genomics Viewer v2.11.3, and only variants previously reported as somatic in hematopoietic or myeloid neoplasms were retained.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-17T17:04:34.416798+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002133","title":"RNA-seq of CPTs","description":"RNA-seq data of CHoroid Plexus Tumors","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002134","title":"ScRNA-seq","description":"ScRNA-seq data of CPOs","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002135","title":"RNA-seq of organoids","description":"RNA-seq data of choroid plexus and telencephalic organoids","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002136","title":"Cell-of-origin profiling in relapsed/refractory large B-cell lymphoma","description":"This study profiled a prospectively enrolled cohort of 116 patients with relapsed/refractory large B-cell lymphoma (R/R LBCL) treated at a single centre (2018–2025), with tissue collected at relapse. Cell-of-origin (COO) was determined by digital gene expression profiling (NanoString LExA120) and a targeted DNA sequencing assay was applied. The dataset supports investigation of COO as a prognostic biomarker in the R/R LBCL setting.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002137","title":"Nanopore Amplicon Sequencing data of 33 patient tumor and one primary cell line samples - all uveal melanoma","description":"Nanopore Amplicon Sequencing data of 4 amplicons in the GNA11, GNAQ, SF3B1 and SRSF2 genes in 33  uveal melanoma patient tumor samples and one primary cell line sample.\r\n\r\nSequencing was performed on a MinION platform (Mk1B) using the SQK-RBK114.24 kit multiplexing 24  samples per flow cell. Basecalling was performed using the dna_r10.4.1_e8.2_400bps_sup@v4.3.0 model and dorado v.0.6.2.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-05T11:32:49.443976+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002138","title":"Longitudinal profiling of ASPSCR1-TFE3 Type 2 Alveolar Soft Part Sarcoma unveils therapeutic targets","description":"Alveolar soft part sarcoma (ASPS) is a rare, highly metastatic soft tissue sarcoma primarily managed through surgery and adjuvant radiotherapy. Discovery of novel treatments is hindered by a scarcity of models to identify genomic vulnerabilities to formulate effective therapeutic trials. We established the first patient-derived xenograft and corresponding cell line from a patient with ASPSCR1-TFE3 Type 2 fusion-positive ASPS. Longitudinal whole genome sequencing, phospho-proteomics, RNA sequencing and drug screening were used to characterize the mutational and clonal landscape of disease progression and identify therapeutic options. ASPSCR1-TFE3 Type 2 fusion expression revealed transcriptional targets including surface proteins such as GPNMB that are being developed for immune- based therapies. Drug screening identified proteasome inhibition as a therapeutic vulnerability and was supported by an upregulation of the ubiquitin-proteasome system in ASPS compared to other solid pediatric cancers. Clinically approved proteasome inhibitors bortezomib and carfilzomib confirmed nanomolar efficacy in vitro and significant tumor inhibition in vivo. Emerging clinical interest within the pediatric and adolescent populations creates an opportunity for evaluation in this rare pediatric population.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002139","title":"Detecting minimal residual disease with ctDNA","description":"Detection of ctDNA in post-treatment plasma samples from patients with triple negative breast cancer can be used to identify patients with residual disease burden, and thus at higher risk of disease recurrence. Circulating tumour DNA carries many of characteristics of the originating tumour cells, including acquired mutations, spanning point mutations, small insertions and deletions, copy number changes, and chromosomal rearrangements, as well as epigenomic features. Here we used whole genome and epigenome sequencing together with tumour-informed and tumour-agnostic ctDNA detection strategies to identify samples with residual cancer burden. We find that combined ctDNA detection approach is sensitive and specific, and is highly predictive of patient outcomes.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002140","title":"High-resolution spatial transcriptomics reveals fibroblast and neuroimmune microenvironments in endometriosis lesions","description":"Endometriosis is a chronic, systemic, inflammatory disease characterized by the presence of endometrium-like tissue growing outside of the uterus. Affecting one in ten individuals assigned female at birth, it causes chronic pain and inflammation that significantly impairs quality of life. Yet the mechanisms that drive pain and disease progression remain poorly defined. This study establishes the precise spatial transcriptomic cartography of human ovarian and peritoneal lesions, two of the most commonly found lesions. Endometriosis lesion tissue was profiled using VisiumV2, VisiumHD, and Xenium spatial transcriptomics platforms. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002141","title":"Single-cell transcriptomic profiling of immune reconstitution after allogeneic hematopoietic stem cell transplantation","description":"Cytomegalovirus (CMV) reactivation is a common and clinically significant complication after allogeneic hematopoietic stem cell transplantation (HSCT), and donor CMV serostatus is known to shape the pace and quality of antiviral immune reconstitution in the recipient. This study longitudinally profiled five allogeneic HSCT donor-recipient pairs, collecting pre-transplant samples from both donors and recipients together with serial recipient blood samples over the first three months after transplantation. Using single-cell RNA and T-cell receptor sequencing, we characterized the maturation and functional dynamics of adaptive natural killer (NK) cells and CMV pp65-specific CD8+ T cells during immune reconstitution. The study aimed to determine how donor CMV serostatus influences the timing, phenotype, and clonal expansion of these antiviral immune populations, providing insight into mechanisms of protection against CMV reactivation after transplantation. ","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[42335212],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002142","title":"Gut microbiota biomarkers associated with Multiple Myeloma: The REMNANT Study","description":"We aimed to investigate the association between gut microbiota composition and multiple myeloma–related clinical parameters, including treatment response, clinical outcomes, and treatment-related adverse effects","abstract":null,"study_type":"Metagenomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-23T15:35:06.889926+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002143","title":"Assessing the impact of combining ICI and TNF blockers on systemic immune responses in melanoma patients","description":"PBMCs from melanoma patients (TICIMEL clinical trial, NCT03293784) were collected before (W0) and after two cycles of ICI (W6 or 7) and anti-TNF. W0 and W6/7 PBMC from 8 patients submitted to CITEseq.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002144","title":"Controlled Human Malaria Infection (CHMI) of malaria-experienced Kenyan adults","description":"Controlled Human Malaria Infection (CHMI) of malaria-experienced Kenyan adults with data collected across a pre-CHMI and two post-CHMI timepoints","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002145","title":"Liquid Biopsy-informed Precision Oncology Study to Evaluate the Clinical Utility of  Non-invasive Genomic Profiling for Cancer Treatment Selection","description":"This dataset pertains to the first planned analysis of an observational trial assessing the clinical utility of serial LB, combined with precision oncology recommendations by a molecular tumor board (MTB). Serial LBs utilized a clinically validated 33-gene panel next-generation sequencing (NGS) assay. Key eligibility criteria included age≥18years, ECOG performance status 0-1, and advanced/metastatic solid tumors with progression on ≥1 lines of therapy. 50 patients were enrolled between March 2023 and July 2024.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-05T11:32:52.460759+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002146","title":"Expansion and cytotoxicity of mucosal T cells in enterocolitis associated with BCMA CAR-T cell therapy","description":"This study investigates immune effector cell enterocolitis (IEC-EC) associated with ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory multiple myeloma. IEC-EC was characterized by infiltration and expansion of clonal CAR-positive cytotoxic T-cell populations within the gastrointestinal tract. Molecular analyses were performed to characterize CAR T-cell clonality, persistence, vector integration, and genomic alterations associated with this complication. This dataset contains whole-genome sequencing (WGS) and whole-exome sequencing (WES) FASTQ files generated as part of the study and associated with the corresponding manuscript.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-29T12:09:39.031021+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002147","title":"IMMUcan SCCHN2 cohort","description":"The goal of IMMUcan is to understand how the immune system interacts with tumors and how therapeutic interventions influence this interaction. This cohort includes HNSCC patients with confirmed progression, after treatment with curative chemo-radiation, to receive salvage surgery. Comprehensive profiling data are integrated with longitudinally collected clinical information. Cellular profiling of the same tumor samples was performed using multiplex immunofluorescence imaging, imaging mass cytometry, and H&E staining.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002148","title":"ERDERA Diagnostic Research Workstream - WGS reanalysis (distributed approach)","description":"The ERDERA Diagnostic Research Workstream – WGS reanalysis (distributed approach) aims to improve diagnostic yield by systematically reanalyzing existing whole genome sequencing (WGS) data from rare disease cases. The goal is to apply updated bioinformatics pipelines, novel variant interpretation tools, and the latest reference databases to detect clinically relevant variants that may have been missed in earlier analyses. By using a distributed approach across multiple expert groups, the project fosters collaborative interpretation and knowledge sharing to enhance diagnostic outcomes for patients.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-29T11:12:39.584913+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002149","title":"RNA-sequencing ","description":"This dataset contains bulk RNA-sequencing performed from the CRISPR/Cas9-engineered model: STAG2 wild-type and STAG2 knock-out NPM::ALK-positive cells collected at day 15 post-transfection.\r\nSequencing was performed with Illumina NovaSeq6000 instrument.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002150","title":"Single-Cell RNA-sequencing","description":"This dataset contains single-cell RNA-sequencing performed from CD4+ T lymphocytes and matched CRISPR/Cas9-engineered model of STAG2 wild-type and STAG2 knock-out NPM::ALK-positive cells collected at day 21 post-transfection.\r\nLibraries were performed using 10x Genomics Chromium Single Cell 5’ Kit (v2) and sequenced on Illumina NovaSeq6000 instrument.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002151","title":"Single cell characterisation of a hepatocellular carcinoma complete regression after immune checkpoint blocker therapy","description":"The hepatocellular carcinoma patient was a 68-year-old male previously diagnosed with an advanced hepatocellular carcinoma (pT2N0M0, BCLC-B) and was treated at University Hospitals Leuven receiving standard-of-care atezolizumab (anti-PD-L1) plus bevacizumab (anti-VEGF) before surgical resection 4 months after. The study was conducted according to EU legislation regarding ethical regulations and registered as a sample acquisition study (S62548). A pre-treatment (prior to 1 dose of pembrolizumab) and a post-treatment tumor sample (collected during resection) were single-cell profiled using Chromium Single Cell V(D)J Solution from 10x Genomics according to the manufacturer’s instructions.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002152","title":"Circulating tumour DNA in oligoprogressing metastatic castration-resistant prostate cancer treated with stereotactic body radiotherapy in the TRAP trial ","description":"The TRAP trial (NCT03644303) reported that stereotactic body radiotherapy (SBRT) of up to two imaging-visible metastases in prostate cancer patients showing disease progression whilst continuing an androgen receptor pathway inhibitor (ARPI) improved outcomes. It is possible that the benefit from treatment is heterogeneous and patients with progressing sub-clinical metastases, not detected by imaging, derived no benefit from this intervention. The goal of this study was to determine if ctDNA levels detected before SBRT associates with worse outcome.\r\n\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-30T09:12:49.932781+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002153","title":"Single-cell profiling of muscle-infiltrating T cells in idiopathic inflammatory myopathies  Study type:","description":"Single-cell RNA sequencing was performed on muscle-infiltrating T cells and paired peripheral blood memory T cells from patients with idiopathic inflammatory myopathies and undefined myopathy. CD45+CD3+ T cells were single-cell sorted from fresh muscle biopsies, while corresponding memory T cells from peripheral blood were sorted in parallel. Healthy controls consisted of peripheral blood memory T cells from three donors. Patient samples were processed using Smart-seq2, while healthy donor samples were processed using Smart-seq3. Libraries were sequenced on an Illumina NovaSeq 6000 using paired-end 2 × 100 bp sequencing.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[37522383],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002154","title":"I-BCT-1 (Improved Breast Cancer Therapy) - WXS","description":"A prospective, randomized neoadjuvant study that evaluates DNA-based biomarkers to identify breast cancer patients most likely to benefit from carboplatin (Cb). While Cb improves outcomes in triple-negative breast cancer (TNBC), responses vary, and its role in aggressive hormone receptor–positive breast cancer (HR+BC) remains uncertain.\r\nPatients (N = 187) with early, high-risk, HER2-negative cT2-4 tumors received 12 weekly paclitaxel with or without Cb, followed by four cycles of epirubicin and cyclophosphamide.\r\n\r\nWhole Exome Sequencing data for normal-tumor pairs from the same subjects is available in the matching study titled I-BCT-1 (Improved Breast Cancer Therapy) - WES","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-01T19:02:10.383405+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002155","title":"I-BCT-1 (Improved Breast Cancer Therapy) - WES","description":"A prospective, randomized neoadjuvant study that evaluates DNA-based biomarkers to identify breast cancer patients most likely to benefit from carboplatin (Cb). While Cb improves outcomes in triple-negative breast cancer (TNBC), responses vary, and its role in aggressive hormone receptor–positive breast cancer (HR+BC) remains uncertain.\r\nPatients (N = 187) with early, high-risk, HER2-negative cT2-4 tumors received 12 weekly paclitaxel with or without Cb, followed by four cycles of epirubicin and cyclophosphamide.\r\n\r\nTranscriptomic analysis data for the tumor samples in this study is available in the matching Study titled I-BCT-1 (Improved Breast Cancer Therapy) - WXS.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-01T19:02:10.600624+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002156","title":"Cryptic mRNA Splicing in FLT3 Internal Tandem Duplications","description":"NGS analyses of genetic material from Acute Myeloid Leukemia cases harboring FLT3 Internal Tandem Duplications to investigate the occurrence of cryptic mRNA splicing.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-06T12:13:33.606418+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002157","title":"Single Cell RNA sequencing of B and T cells in ANCA-associated vasculitis patients","description":"To identify ANCA-specific B cells, we performed deep single-cell profiling of B cells and their B cell receptor repertoire in fifteen AAV patients from the ENDURRANCE randomized controlled trial, comparing to age-matched HCs (n=5). Single Cell RNA sequencing of T cells and T cell receptor repertoire was performed on these patients and an additional three AAV patients from the Stanford Vasculitis Clinic (total n=18) and an additional six HCs.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002158","title":"An Asian pangenome reveals ancestry-stratified diversity and geographic introgression","description":"We present the Asian Pangenome Consortium pilot phase (APC-P1), a long-read pangenome built from 260 haplotype-resolved genomes spanning 47 ethnolinguistic groups across nine Asian countries and regions, including deeply diverged Indigenous lineages absent from prior global pangenomes. APC-P1 reveals extensive, ancestry-stratified rare and population-specific structural variation, bridging East Asian–focused and globally diverse pangenome resources with more balanced population representation. Haplotype-resolved analysis shows Neanderthal introgression is widespread and homogeneous across Asia, while Denisovan introgression is geographically localized and enriched in Indigenous Southeast Asian groups, identifying Southeast Asia as a key axis of archaic admixture. Repeat-rich loci such as NBPF1 show deep population stratification linked to gene expression, and population-aware graphs substantially improve short-read SV genotyping in Asian cohorts. At clinically relevant loci (LCE3B/C, APOBEC3B, FCGR2C, CYP2D6), complex structural haplotypes reshape interpretation of GWAS and pharmacogenomic signals, establishing population-aware pangenomes as essential tools for Asian human genomics.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002159","title":"IMMUcan CRC1 cohort","description":"The goal of IMMUcan is to understand how the immune system interacts with tumors and how therapeutic interventions influence this interaction. This cohort includes patients with a confirmed diagnostic of metastatic colorectal adenocarcinoma. Comprehensive profiling data are integrated with longitudinally collected clinical information. Cellular profiling of the same tumor samples was performed using multiplex immunofluorescence imaging, imaging mass cytometry, and H&E staining.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002160","title":"Scalable proxiloids enable human-relevant assessment of kidney proximal tubule toxicity","description":"hiPSC-derived \"proxiloid\" organoids for modeling human kidney proximal tubule (PT) drug toxicity. 14-day scalable suspension culture combining PT-enriched tubular architecture, transporter function, and oxidative metabolism. Validated with etoposide (DNA-damage response), gentamicin (aminoglycoside nephrotoxicity), and adefovir (mitochondrial toxicity).","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002161","title":"RHOV regulates CD4⁺ T-cell–mediated type 2 inflammation in allergic rhinitis","description":"Integrated transcriptomic analyses were performed using peripheral blood mononuclear cells (PBMCs) from AR patients and healthy controls, as well as in vitro-polarized Th2 cells. \r\nIntegrated transcriptomic analyses identified Ras homolog family member V (RHOV) as a commonly upregulated gene associated with Th2 polarization and AR.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002162","title":"IMMUcan Dutrelasco SCCHN4 cohort","description":"The goal of IMMUcan is to understand how the immune system interacts with tumors and how therapeutic interventions influence this interaction. This cohort includes patients from the DUTRELASCO trial:  sequential tumor tissue acquisition in patients with newly diagnosed advanced (stage IV) oral cavity SCC. Patients are treated with Durvalumab (arm A) or Durvalumab + Tremelimumab (arm B) after biopsy-confirmed diagnosis of locally advanced resectable SCCHN of the oral cavity. After surgery, the standard of care treatment is radiotherapy, and, depending on risk assessment concurrent cisplatin. Patients will be treated with Durvalumab (arm A) or Durvalumab and Tremelimumab (arm B) during six additional cycles, starting from day one of the postoperative radiotherapy. Comprehensive profiling data are integrated with longitudinally collected clinical information. Cellular profiling of the same tumor samples was performed using multiplex immunofluorescence imaging, imaging mass cytometry, and H&E staining.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002163","title":"NoSarC -- Norwegian Sarcoma Consortium. Towards individualized therapy for orphan cancer.","description":"This study is initiated and conducted by the Norwegian Sarcoma Consortium - a collaboration between 5 Norwegian hospitals and universities, coordinated by Oslo University Hospital.\r\n\r\nThe NoSarC project was initiated in 2014 and aimed to perform molecular characterization of samples from a national, population-based cohort of sarcoma patients, to identify tumors which are sensitive to therapies already developed and approved for more common cancers.\r\n\r\nThe NoSarC cohort in this study consists of Tumor-Normal pairs from 287 subjects that has been Whole Exome Sequenced.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-09-23T17:14:04.878906+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002164","title":"IMMUcan CRCKUL CRC1 cohort","description":"The goal of IMMUcan is to understand how the immune system interacts with tumors and how therapeutic interventions influence this interaction. This cohort includes patients with early-stage colorectal adenocarcinoma. Comprehensive profiling data are integrated with longitudinally collected clinical information. Cellular profiling of the same tumor samples was performed using multiplex immunofluorescence imaging, imaging mass cytometry, and H&E staining.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002165","title":"TLS-associated B cell repertoire shaping and response to immune checkpoint inhibitors in patients with renal cell cancer","description":"All raw and processed data necessary to reproduce main and supplementary figures related to the article. 4 datasets: Ig-inferred with MiXCR from bulk RNAseq of ccRCC tumors (n=95) ; Ig-targeted capture in bulk (Immunoverse) from ccRCC tumors & blood before and after treatment paired patient’ samples (n=96) ; Ig-targeted capture in spatial transcriptomics (SpatialVDJ) from ccRCC tumor sections (n=4) ; Ig-inferred with MiXCR in spatial transcriptomics from ccRCC tumor sections included in Meyan et al, 2022, Immunity paper (n=12). Scripts are available on GitHub (github.com/GuiPupier/Ig_TLS_ICI). Note that additional files not deposited in EGA are available in a complementary Zenodo repository (named \"title  - Additional files supporting the EGA submission\").","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002166","title":"VAPA-dependent lipid transport in alveolar epithelial type 2 cells promotes lung surfactant formation","description":"VAP proteins form membrane contact sites (MCS) between the endoplasmic reticulum (ER) and other organelles through interactions with FFAT-containing proteins, thereby coordinating lipid synthesis, transfer, and metabolism. However, their tissue-specific functions remain largely unexplored. Here, we report the first patient with a homozygous nonsense variant in VAPA (p.(Glu12*)), presenting with profound global developmental delay and progressive surfactant dysfunction leading to cholesterol pneumonitis and pulmonary fibrosis. Alternative translation initiation partially bypasses the premature stop codon, resulting in an N-terminally truncated VAPA protein with impaired FFAT-binding capacity. In alveolar type 2 cells, VAPA deficiency impairs lamellar body (LB) formation. We identify the pulmonary disease-associated ATP-binding cassette transporter A3 (ABCA3), a key regulator of surfactant lipid accumulation in LBs, as a novel VAPA interactor. The VAPA–ABCA3 interaction facilitates lipid exchange at previously uncharacterized ER–LB MCS, a function that is lost upon N-terminal truncation of VAPA. Together, our findings identify impaired VAPA-dependent MCS function as a mechanism underlying syndromic lung disease and reveal a previously unrecognized pathway for surfactant lipid trafficking.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-13T09:56:09.006255+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002167","title":"WES and RNA-seq of patient-derived tumor organoids (PDAC/HNSCC) under CAP treatment","description":"Six patient-derived tumor organoid (PDTO) lines were established from patients with pancreatic ductal adenocarcinoma (PDAC, n=3) and head and neck squamous cell carcinoma (HNSCC, n=3). PDTOs were treated with cold atmospheric plasma (CAP) for 30 s (PDTO1–2) or 150 s (PDTO3–6) or left untreated. Whole-exome sequencing (WES, 100x coverage) was performed on one biological replicate per condition, and RNA sequencing (TruSeq total RNA) was performed on three biological replicates per condition, using a NovaSeq X Plus platform (Genomics Core Leuven). This data characterizes genomic and transcriptomic responses to CAP treatment across two cancer types, revealing interpatient heterogeneity.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002168","title":"Evolutionary dynamics in the decades preceding acute myeloid leukaemia","description":"Somatic evolution in ageing tissues underlies many cancers, yet the quantitative rules governing pre-cancerous evolution remain incompletely understood. This study exploits a collection of serial blood serum samples from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), collected annually from as early as 15 years before a diagnosis of acute myeloid leukaemia (AML), to provide a quantitative description of pre-cancerous evolutionary dynamics. Longitudinal samples from women who subsequently developed AML, alongside timepoint-matched samples from age-matched cancer-free controls, were sequenced using TETRIS-seq, a deep duplex error-corrected sequencing approach covering a custom panel of single-nucleotide variants and indels, mosaic chromosomal alterations, and chromosomal rearrangements associated with clonal haematopoiesis and AML. Combined with evolutionary modelling, these data quantify the acquisition ages and fitness effects of key driver events in AML development, characterise the clonal dynamics that precede diagnosis, and show that pre-leukaemic evolution is consistent with a small set of evolutionary rules balancing chance and determinism. The deposited data comprise raw paired-end FASTQ files for all sequenced samples.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-05T11:37:44.136598+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002169","title":"scRNA-sequencing data of 14 duodenum samples for Cirrhosis study","description":"14 samples of scRNA-sequencing data. Duodenum samples of 14 patients (human) that are healthy volunteers (3), with compensated cirrhosis (5) or decompensated cirrhosis (6) were sequenced for scRNA-seq. We wanted to see, transcriptionally what differs between HV, CC and DC patients. The sequencing was mainly done on the epithelial layer of the duodenum. \r\n","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002170","title":"IMMUcan CRCCLB CRC1 cohort","description":"The goal of IMMUcan is to understand how the immune system interacts with tumors and how therapeutic interventions influence this interaction. This cohort includes metastatic colorectal Adenocarcinoma from Hopital Centre Leon Berard (Lyon, France). Comprehensive profiling data are integrated with longitudinally collected clinical information. Cellular profiling of the same tumor samples was performed using multiplex immunofluorescence imaging, imaging mass cytometry, and H&E staining.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002171","title":"Association of OXTR and AVPR1A Genetic Variation with Empathy and Dark Triad Traits in a Non-Clinical Human Sample","description":"This study investigates associations between variation in OXTR and AVPR1A, empathy, and Dark Triad personality traits in 506 participants from a non-clinical human sample. OXTR rs53576 and rs2254298 were genotyped using TaqMan assays, while AVPR1A RS1 and RS3 microsatellites were characterized by capillary electrophoresis and fragment-length analysis. Empathy was assessed using the Interpersonal Reactivity Index (IRI), and Machiavellianism, narcissism, and psychopathy were assessed using the Short Dark Triad (SD3). The study evaluates direct genotype–phenotype associations and indirect associations involving specific dimensions of empathy.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002172","title":"Endogenous SMN Heterogeneity Defines Dynamic States of Motor Neuron Vulnerability and Resilience","description":"Dataset includes bulk-RNA-sequencing data of hiPSC-derived motor neurons (as described in Grass et al. Cell Reports Medicine 2024) expressing SMN-Clover protein. hiPSC-MNs were FACSorted into into high-SMN, mid-SMN, and low-SMN bins at either 4 or 12 days-in-vitro (DIV) to investigate potential mechanisms that determine selective neuronal vulnerability as indicated by SMN expression.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002173","title":"Filtered adipose-derived regenerative cell lysate (F-ADRCL) enhances wound healing","description":"We investigated the wound-healing effects of F-ADRCL in vivo and in vitro. Full-thickness skin wounds were created on the backs of wild-type mice and treated with F-ADRCL. Treatment with F-ADRCL promoted wound healing compared with control. In HUVECs, F-ADRCL enhanced lumen-forming ability, suggesting enhancement of peri-wound capillary formation.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002174","title":"Transcriptomics data","description":"This study includes bulk RNAseq data of advanced solid tumors.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-14T15:57:15.976048+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002175","title":"Genomic data","description":"This study includes genomic data of advanced solid tumors.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-14T15:57:18.865841+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002176","title":"WGS data from TSC2 patient (p24 #4) derived hiPSC","description":"This dataset contains whole genome sequencing data of a patient IPS cell line with a heterozygous mutation in TSC2 (Patient 2 TSC2+/- iPSCs; also referred to as p24/Patient 24 in the connectomics manuscript).","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002177","title":"WGS data from ARID1B patient (p2 #8) derived hiPSC","description":"Whole genome sequencing data of a patient hiPSC cell line derived from patient ARID1B p2 clone #8. Data was used for the analysis of neurological consequences of ARID1B mutations in in vitro human neural organoids","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002178","title":"Raw 10x single-cell RNA-seq data of rabies-traced control and TSC human cerebral organoids (COSCO)","description":"This dataset contains raw 10x Genomics Chromium 3' (v3.1) single-cell RNA-seq data from 25 samples. Each samples pools rabies-traced cells, cell-type composition control cells, and uninfected true-negative cells from a genetically distinct line. Organoids came from six lines (H9 hESC, 177 hiPSC, two TSC2+/- hiPSC lines, and their isogenic controls) at 120 or 150 days in vitro. Samples were sequenced on Illumina NovaSeq S2 or S4 flow cells (paired-end, target of 50,000 reads per cell), yielding 219,650 cells before quality control and 113,757 high-quality cells after filtering.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002179","title":"Genomics of Grecìa Salentina: search for possible source populations for the Greek-speaking enclave of Apulia (Italy)","description":"In order to represent the genomic landscape of the continental areas that may have contributed to the GS gene pool, we included our original data into dataset of 503,578 (500K dataset) strictly biallelic SNPs in non-repetitive DNA regions, LD-pruned, with MAF >= 0.03 and less than 2% missing genotypes. We also used another set of 997 variants, previously described as strong Ancestry Informative Markers, specifically for the European populations, and nearly entirely independent of the 500K dataset.\r\n","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002180","title":"Cytotoxic effector transcriptional imprinting in circulating T cells underpins response to adoptive T cell therapy in glioblastoma","description":"Adoptive T-cell therapy (ACT) has shown therapeutic potential in glioblastoma (GBM), yet biomarkers predicting durable clinical benefit remain undefined. In a phase I trial of autologous cytomegalovirus (CMV)-specific ACT, we previously identified survival-associated transcriptional states within T cell therapy drug products. Here, using single-cell RNA sequencing with paired T-cell receptor sequencing of matched pre- and post-treatment peripheral blood from long-term survivors (LTS) and short-term survivors (STS), we demonstrate that response to ACT is strongly conditioned by the host immune landscape. LTS patients displayed a pre-existing cytotoxic CD8/NK-associated program enriched for NKG7, CCL5 and granzymes that persisted after therapy and correlated with prolonged survival, whereas STS patients were enriched for a CCR7- and LEF1-associated CD4+ T-cell state linked to poor outcome. Expanded and persistent clonotypes localized predominantly within cytotoxic CD8+ T cell populations in LTS patients, including T cell therapy-derived CMV-specific clonotypes detected after adoptive immunotherapy. Notably, the survival-associated cytotoxic program extended beyond CMV-specific clonotypes, identifying a broader immune architecture associated with durable therapeutic response. These findings reveal that ACT efficacy in GBM is determined not only by the infused cellular therapy, but also by pre-existing systemic immune competence and the capacity to sustain cytotoxic T-cell programs after therapy. Our study provides a translational framework for integrating baseline single-cell immune profiling into patient stratification and biomarker-guided ACT trials in GBM.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002181","title":"Characterisation of cellular and transcriptional changes of human liver diseases using snRNA-seq","description":"This study aimed to characterize cellular and transcriptional changes in human liver tissue across different stages of primary sclerosing cholangitis and other liver diseases. Fresh-frozen liver samples were obtained during clinical care at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany, and processed for 10x Genomics snRNA-seq, 3'-single-nucleus RNA sequencing. Sequencing reads were aligned to the human GRCh38 reference genome using Cell Ranger. The resulting BAM files are provided here.\r\n","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002182","title":"Multiomic Analysis of Treatment Naive MYD88 Mutated Patients with Waldenstrom’s Macroglobulinemia","description":"This study consists of RNASeq with additional whole exome sequencing and enhanced reduced representational bisulfite sequencing for a subset of study participants. Samples were derived from CD19 selected bone marrow biopsies. Deidentified clinical annotation of these samples is also included. Samples range from patients at the earliest stages of disease development to those who are about to initiate therapy. The aim of this study is to look for clinical/molecular subtypes of WM and study the biology of disease evolution/progression.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-19T10:02:41.168541+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002183","title":"Bladder cancer genomic sequencing data from exclusive waterpipe tobacco smokers - AUBMC cohort","description":"Raw sequencing data from 13 bladder cancer patients at the American University of Beirut Medical Center (AUBMC, Lebanon) with exclusive waterpipe tobacco use, profiled by MSK-IMPACT® targeted sequencing and whole-exome sequencing (TEMPO pipeline). Data were generated as part of a cross-sectional genomic study comparing bladder cancer in waterpipe smokers, cigarette smokers, and never-smokers to characterize mutational signatures, tumor mutational burden, and oncogenic pathways.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-14T16:09:56.822592+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002184","title":"Somatic variant detection using an individual-specific pangenome reference: a case study of a pediatric acute myeloid leukemia patient","description":"Reference bias remains a key challenge in somatic variant calling, which pangenomes aim to address. However, systematic evidence for the diagnostic benefit of the pangenomic approach is lacking. We characterize how an individual-specific pangenome reference affects somatic variant calling across diverse cell types at the bulk and single-cell levels.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002185","title":"IMMUcan CRCStLuc CRC1 cohort","description":"The goal of IMMUcan is to understand how the immune system interacts with tumors and how therapeutic interventions influence this interaction. This cohort includes patients with metastatic colorectal adenocarcinoma from Hopital St-Luc (Brussels, Belgium) Comprehensive profiling data are integrated with longitudinally collected clinical information. Cellular profiling of the same tumor samples was performed using multiplex immunofluorescence imaging, imaging mass cytometry, and H&E staining.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002186","title":"High prevalence of CHIP after 177Lu-DOTA-TATE","description":"In Neuroendocrine tumors (NETs), 177Lu-DOTA-TATE peptide receptor radionuclide therapy (PRRT) has demonstrated efficacy but significant hematologic toxicity, including therapy-related myeloid neoplasms (t-MN). Here, we assessed the prevalence of clonal hematopoiesis (CHIP), a known risk factor for therapy-related myeloid neoplasms (t-MN), according to previous PRRT exposure.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002187","title":"Healthy aging KCL cohort PBMC","description":"PBMC single-cell transcriptomic profiling was performed to characterize age-associated changes in immune cell composition, cellular states, and gene expression programs during healthy aging.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-15T13:53:23.072843+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002188","title":"Subtype-specific mutational landscapes in core-binding factor AML identify recurrent ZBTB7A alterations in t(8;21) AML","description":"This study investigates subtype-specific mutational profiles in core-binding factor acute myeloid leukemia (CBF-AML) using whole-exome sequencing. The dataset includes 16 patients with CBF-AML, comprising 11 patients with t(8;21) and 5 patients with inv(16). The study also evaluates recurrent ZBTB7A alterations in t(8;21) AML.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-13T10:08:13.304789+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002189","title":"Genomic analysis of Korean never-smoker lung adenocarcinoma patients (2nd study)","description":"This study investigates the genomic characteristics of lung adenocarcinoma in Korean never-smoker patients. Whole-genome sequencing was performed to characterize genomic alterations in tumor and matched normal samples. Sequencing data were generated using the Illumina NovaSeq 6000 platform and processed following the GATK Best Practices pipeline.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002190","title":"Genomic correlates with survival after treatment of oesophageal adenocarcinoma by surgery alone","description":"A 451 cancer-associated gene panel, described in McCabe et al. 2019, was used to assess genomic alterations associated with survival in a Swedish cohort of 65 oesophageal adenocarcinoma (OAC) patients who underwent surgical resection without perioperative treatment. Primary tumour tissues and matched normal squamous oesophagus tissues were collected from each individual. Laboratory studies were performed at the Centre for Applied Medical Research (AMR) and sequencing was performed at the Kinghorn Cancer Centre. 64 of 65 cancer samples and 61 matched squamous oesophageal mucosa control tissues were successfully sequenced and passed minimal quality metrics.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[31745186],"external_links":null,"is_released":true,"released_date":"2026-10-13T09:58:40.796686+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002191","title":"Whole-exome sequencing of HR+/HER2- metastatic breast cancers from the EPICURE_SEIN cohort","description":"This dataset contains whole-exome sequencing data from tumor samples collected in the prospective EPICURE_SEIN study (NCT03958136) . This dataset accompanies the study “Multi-omics prediction of progression in HR+/HER2- metastatic breast cancer on CDK4/6 inhibitors plus endocrine therapy”.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002192","title":"Paired single-cell RNA-seq and B-cell receptor sequencing of CSF and blood B cells from 8 individuals with multiple sclerosi","description":"Single-cell 5' gene expression (scRNA-seq) and paired B-cell receptor (BCR) VDJ libraries from cerebrospinal fluid and peripheral blood mononuclear cells of 8 patients with multiple sclerosis, sampled longitudinally at up to three timepoints. Libraries were generated with the 10x Genomics Chromium platform and sequenced on Illumina NovaSeq 6000 and NovaSeq X Plus. The dataset comprises 32 samples and 832 raw FASTQ files under controlled access.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002193","title":"N-terminal truncation diversifies USP18 function during early myogenesis","description":"Ubiquitin-specific protease 18 (USP18) is primarily studied for its dual role in type-I interferon (IFN-I) signaling, acting as an ISG15 deISGylase and a non-catalytic inhibitor of IFNAR signaling. At basal levels, however, USP18 also regulates muscle cell development, independently of IFN-I signaling. USP18 exists as a canonical long isoform (LF) and a short isoform (SF) generated by N-terminal truncation. Endogenous SF accumulates in the nucleus during muscle differentiation, but its cellular functions remain poorly understood. Here, we compared SF and LF in muscle cells stably overexpressing each isoform. We show that their distinct N-termini are associated with marked differences in protein stability, subcellular localization, and protein–protein interactions. SF displayed a substantially expanded interactome, with increased association with nuclear proteins, chaperones, and regulators of protein homeostasis. Functionally, SF enhanced an early stage of myogenic differentiation and was associated with changes in alternative splicing, including among key sarcomere genes. Together, these findings identify the SF USP18 proteoform as a potential regulator of muscle differentiation and highlight the N-terminus as a determinant of non-canonical USP18 functions and proteoform diversity.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002194","title":"scRNA-sequencing data of 10 healthy human duodenum samples - Prof Tim Vanuytsel","description":"Duodenal biopsies from 10 healthy human donors, used as controls. The dataset supports two separate investigations: the duodenal consequences of cirrhosis, and the pathophysiology of short bowel syndrome together with the therapeutic effect of apraglutide. We used 10X scRNA-seq. ","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002195","title":"Longitudinal bulk B- and T-cell receptor repertoire sequencing from the DNG2002 dengue virus 3 human challenge study","description":"Longitudinal bulk B- and T-cell receptor repertoire sequencing data generated from participants enrolled in the DNG2002 dengue virus 3 human challenge study. The dataset comprises UMI-based AIRR-seq libraries generated from longitudinal whole-blood samples collected before and after controlled DENV-3 infection. It includes raw sequencing reads and processed immune-repertoire data for immunoglobulin heavy-chain and T-cell receptor libraries. The data support analyses of repertoire composition, clonal dynamics, molecular complexity, sequencing depth, and host adaptive immune responses over the course of infection. The dataset is intended to support both methodological studies of AIRR-seq and biological analyses of the longitudinal immune response to controlled DENV-3 infection.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-20T17:16:24.279287+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002196","title":"Visium Spatial transcriptomic profiling of IOKIN samples","description":"This study aimed to define the spatial tumor microenvironment features associated with response to immune checkpoint blockade in recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC). Spatial transcriptomic profiling was performed on tumor biopsies from ICB-naive patients to characterize malignant, stromal, and immune cell states and their spatial interactions. The study investigated how intratumoral heterogeneity, cancer-associated fibroblast programs, immune contexture, and tumor-microenvironment signaling relate to subsequent clinical response and progression-free survival following immunotherapy.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-14T16:04:58.545537+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002197","title":"Multi-omic profiling of DMG multi-site samples","description":"Multi-omic profiling of diffuse midline glioma multi-site biopsy and autopsy samples","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002198","title":"Cellular plasticity drives regeneration of heterogeneity in hepatocellular carcinoma organoids","description":"Using patient-derived HCC organoids (HCCOs), we investigated the cellular basis of heterogeneity in HCC.We performed single-cell outgrowth assays and scRNAseq of sublines and the original parental HCCO.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002199","title":"WES of single-cell derived HCCOs","description":"To investigate the genomic basis underlying the observed phenotypic and transcriptional heterogeneity in HCCOs, we performed whole-exome sequencing (WES) on three originating HCCO lines together with their respective clonal derivatives. For each originating HCCO, six first-generation scd-HCCOs were sequenced. Additionally, six second-generation scd-HCCOs derived from two of the first-generation clones were included to assess genomic stability following an additional single-cell bottleneck.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002200","title":"Single-cell transcriptomic profiling of ASPM-mutant and isogenic control human cortical organoids","description":"This study investigates the impact of pathogenic ASPM disruption on human cortical development using an isogenic human iPSC-derived cortical organoid model. Single-cell RNA sequencing was performed on control CtAH4 organoids and the CRISPR/Cas9-engineered ASPM-mutant derivative M5AH4-3a at differentiation days 36, 56 and 70. Libraries were generated using 10X Genomics Chromium Single Cell 3′ v3.1 Next GEM chemistry and sequenced on MGISEQ-2000 and Illumina NovaSeq 6000 platforms.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002201","title":"Prognostic value of intra-tumoral heterogeneity in stage II colorectal mucinous adenocarcinoma","description":"This study includes 187 patients with stage II colorectal mucinous adenocarcinoma and uses copy number heterogeneity (CNH) as a surrogate for intratumoral heterogeneity (ITH) to investigate its prognostic significance.We aim to assess the association between CNH and clinical outcomes.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002202","title":"Epigenetic Drivers of Localised Prostate Cancers Reveal Neuronal and Microenvironmental Reprogramming and Inform Liquid Biopsy Biomarkers","description":"This study aimed to identify epigenetic drivers of localised prostate cancer and to determine which cell types they arise from. We generated whole genome methylation profiles of FACS-sorted prostate cell populations to build a reference methylation atlas of the major epithelial, stromal, and immune cell types. In addition, plasma cell-free DNA from prostate cancer patients and buffy coat from non-prostate-cancer control donors were also profiled. This atlas was used to assign tumour-specific differentially methylated regions to their cell types of origin and to identify cell-type-specific methylation signatures. These signatures informed the interpretation of tumour subtypes, microenvironmental remodelling and cell-informed liquid biopsy biomarkers.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002203","title":"Bulk RNA sequenicng of soft tissue sarcoma tumours ","description":"This study investigates gene expression profiles across 196 soft tissue sarcoma tumours, encompassing liposarcoma, leiomyosarcoma, undifferentiated pleomorphic sarcoma and synovial sarcoma, using bulk 3′ mRNA sequencing.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002204","title":"Nicking Loop POC","description":"Study evaluates performance of the Nicking Loop targeted library preparation technology on composite DNA samples. Two samples were sequenced on Illumina MiSeq.  ","abstract":null,"study_type":"Resequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002205","title":"WGS of RPE-1 subclones that were exposed to DMSO, BaP, or PM2.5","description":"RPE-1 are a retinal pigment epithelial cell line that have been previously used to derive mutational signatures in vitro. An RPE-1 TP53-/- grandparent clone was generated and then exposed to either DMSO (negative control), 5 uM BaP continuously (positive control) or 200 ug/mL PM2.5 in six 24-hour pulse exposures before undergoing clonal selection again. Three to four daughter clones from each exposure group as well as the grandparent clone were sent for WGS to derive mutational signatures resulting from PM2.5 exposure.","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002206","title":"WES of LCNS who have never smoked with defined PM2.5 exposure levels","description":"This project aimed to understand the exonic landscape of lung adenocarcinoma patients who have never smoked (LCNS) with defined levels of past 20-year PM2.5 exposure calculated by residential addresses. These patients all received lung resection at Vancouver General Hospital or Surrey Memorial Hospital in British Columbia, Canada between 2019-2025. The samples sequenced for each patient include FFPE tumour and matched normal tissues.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002207","title":"Single-cell profiling reveals conserved epithelial composition and CFTR expression in human nasal epithelial and BCi airway cultures.","description":"We generated single-cell RNA-sequencing profiles from differentiated human nasal epithelial (HNE) cells obtained from one healthy donor and from the immortalized human airway basal cell line BCi-NS1.1. Both models were differentiated under air-liquid interface conditions for 30 days before cell dissociation, single-cell partitioning, barcoding, and sequencing using the 10x Genomics Chromium Single Cell 3′ Reagent Kit v4. The dataset contains approximately 30,146 cells and was generated to compare epithelial cell composition and CFTR expression between primary HNE-derived and BCi-derived airway epithelia. The data identify basal, suprabasal, ciliated, deuterosomal, secretory, goblet, ionocyte, macroalveolar, and neuroendocrine populations and support evaluation of BCi-NS1.1 as a complementary model for cystic fibrosis airway research.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-19T15:40:48.372156+02:00","is_deprecated":false},
{"accession_id":"EGAS50000002208","title":"Navigating the rapidly evolving landscape of sequencing-based spatial transcriptomics technologies: a comprehensive multi-platform benchmark","description":"These datasets are part of a study in which we presented a systematic benchmarking of a diverse set of sequencing-based spatial transcriptomics platforms across multiple tissue types and preservation methods, allowing direct comparison of their technical specifications, capture efficiency, spatial accuracy, cost and practical usability. Specifically, we evaluated performance across mouse brain, mouse liver, mouse lung, human lung and rice root for BMKMANU S1000, BMKMANU S3000, Curio Seeker, Nova-ST, Stereo-Seq, Visium, Visium HD, and Visium HD 3’.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002209","title":"Comprehensive molecular characterization of cutaneous squamous cell carcinoma reveals determinants of metastatic progression","description":"Cutaneous squamous cell carcinoma (cSCC) is the second most common form of cancer worldwide. To better understand what causes some cSCCs to progress to metastatic disease, we assembled a nationwide cohort of 19,120 patients with clinico-pathologically annotated tumors linked to metastatic outcome. Whole-exome sequencing was performed on 147 patients, with balanced numbers of tumors that progressed to metastatic disease (cases) and did not (controls). Together, these findings provide the most detailed molecular portrait of cSCC to date and establish an assay for risk stratification suitable for clinical implementation.\r\n","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002210","title":"Transcriptomic profiling of human colonic organoid-derived epithelial monolayers cultured in a gut-on-chip model and conventional cell culture inserts","description":"This study comprises bulk RNA sequencing data from human colonic organoid-derived epithelial monolayers cultured in the Human-Microbial Crosstalk (HuMiX) gut-on-chip model or conventional cell culture inserts. Samples include the inoculum consisting of undifferentiated dissociated organoids grown in Matrigel domes and differentiated monolayers collected after 9 days of culture. Monolayers in HuMiX were exposed to Lacticaseibacillus rhamnosus GG (LGG) for 24 h, while monolayers in inserts were exposed to LGG-conditioned medium for 24 h. The dataset enables comparative analysis of epithelial differentiation and responses to microbial stimuli across dynamic and conventional intestinal culture systems. Three independent experiments were performed using organoids established from a single donor.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002211","title":"Multimodal Study of Malignant Rhabdoid Tumors","description":"Original Manuscript Title: \"MET inhibition exploits conserved regulatory dependencies in malignant rhabdoid tumors\" |\r\n\r\nSingle-cell multi-omic profiling (Chromium Single Cell Multiome ATAC + Gene Expression, 10X Genomics, n=16 patients) and spatial transcriptomics across anatomically and molecularly diverse malignant rhabdoid tumors (Visium, 10X Genomics, n=11 patients).","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002212","title":"Mitigating genotype-driven bias improves atlas-scale single-cell DNA methylome profiling","description":"Single-cell DNA methylation studies often include cells from individuals with distinct genotypes, where C-to-T variants are misread as bisulfite-converted unmethylated cytosines, conflating genotype with DNA methylation differences. We mitigate this variant-driven bias by masking variant positions before DNA methylation quantification and feature selection. Using sciMET profiles of blood nuclei from eight healthy donors with diverse genetic backgrounds, we show that masking reduces donor-associated confounding in clustering and spurious sample-specific differentially methylated regions within the same cell type. This provides practical solutions for improving single-cell DNA methylation analyses in atlas-scale, pooled experimental designs.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002213","title":"Human fibrosarcoma","description":"RNAseq data of tumour and matched normal tissue from human fibrosarcoma patients. Tissue was isolated from archived FFPE blocs using laser-capture microdissection.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002214","title":"Human myxofibrosarcoma","description":"RNAseq data of tumour and matched normal tissue from human myxofibrosarcoma patients. Tissue was isolated from archived FFPE blocs using laser-capture microdissection.","abstract":null,"study_type":"Transcriptome Analysis","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002215","title":"Prehistoric global migration of vanishing gut microbes with humans","description":"The gut microbiome is crucial for health and is affected strongly by lifestyle. Many microorganisms commonly found in non-industrialized populations are disappearing or have become extinct in industrialized populations. Studying which microorganisms have been long-term residents of the human gut and may have co-evolved with humans could provide insights into how microbial biodiversity loss affects human health. However, the genetic complexities of microbial evolution and the plasticity of gut microbiome composition have made it challenging to resolve the evolutionary history of these long-term associations. Here we performed deep metagenomic sequencing of the Tsimane horticulturalists of Bolivia and compared their gut microbiomes with those of the Hadza hunter-gatherers of Tanzania. These two populations, whose ancestors have been separated for tens of thousands of years, share 1,231 microbial species, most of which are rare in or absent from industrialized populations. Population genetic analyses of 636 of the shared species revealed patterns of microbial divergence and gene flow consistent with prehistoric human co-migration, with estimated split times that approximately align with human migration out of Africa and into the Americas. Our findings indicate that a diverse gut microbiome co-migrated with humans worldwide and has persisted over millennia. However, many of these species are now vanishing from industrialized populations and the consequences for human health remain uncertain.","abstract":null,"study_type":"Metagenomics","pubmed_ids":[42844483],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002216","title":"Lung cancer subtyping using cell-free DNA fragmentomes","description":"\"The treatment of lung cancer depends on its subtype, histology, and stage, but tissue biopsies may be challenging in a subset of patients. Here we used machine learning analyses of genome-wide copy number characteristics of 822 lung cancer samples from the Clinical Lung Cancer Genome Project to develop classifiers to distinguish lung cancer subtypes, including small cell lung carcinoma (SCLC) and two non-small cell lung cancer (NSCLC) subtypes, lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). We used these molecular classifiers to evaluate genome-wide sequences of cell-free DNA (cfDNA) fragments from 653 patients in the LEMA prospective observational trial, and observed a high performance for distinguishing SCLC from NSCLC (AUC=0.98, 95% CI=0.96-1), and for classifying LUAD compared to LUSC (AUC=0.87, 95% CI=0.83-0.91). The cfDNA subtyping approach was validated in a separate cohort of NSCLC patients (n=75). Patients with a cfDNA classification of SCLC had a worse prognosis than those with cfDNA classification of NSCLC (HR=2.26, 95% CI=1.67-3.06, p<0.0001), even among those who were thought to have NSCLC by pathologic criteria. Individuals with pathologically confirmed transformation from NSCLC to SCLC were independently detected using cfDNA analyses. This cfDNA fragmentome method provides an avenue for non-invasive lung cancer subtyping to guide treatment selection and improve clinical outcomes.\r\n\r\nProject goal: The aim of this study was to develop a cfDNA fragmentome classifier trained to recognize genomic copy number patterns associated with LUAD, LUSC and SCLC, and to evaluate its ability to noninvasively distinguish between these lung cancer subtypes in the prospective observational Lung Cancer Early Molecular Assessment (LEMA) trial (NCT02894853). Baseline, pre-treatment blood samples were collected from patients enrolled across 10 sites in the Netherlands between August 2016 and December 2019, and plasma cfDNA was analyzed by low-coverage (~4x) whole-genome sequencing. This dataset contains the cfDNA sequencing data of the 653 LEMA patients with LUAD, LUSC or SCLC included in the subtyping analyses.\"\r\n","abstract":null,"study_type":"Whole Genome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002217","title":"Single cell RNAseq data of colon biopsies from a colitis ulcerosa patient","description":"This project aimed to characterize longitudinal changes to the immune, stromal, and epithelial cell composition and transcriptional profile of colon biopsies following CD19.CAR-T cell therapy of a colitis ulcerosa patient. The sequencing data are derived from a single patient that was treated with CAR T cells in an experimental treatement attempt and was generated in multiple sequencing runs at the time points of sampling. The longitudinal profiling allowed comparisons of pre treatment samples with the samples after treatment to analyze transcriptional changes and cell type composition after B cell depletion.  ","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002218","title":"RNA sequencing of metastatic melanoma tumor biopsies from patients treated with immune checkpoint blockade: association with circulating LDH isoenzyme profiles","description":"This study includes bulk RNA sequencing data generated from tumor biopsies of patients with unresectable or metastatic melanoma treated with immune checkpoint blockade (anti-PD-1 monotherapy or combined anti-PD-1/anti-CTLA-4). Samples were collected at Gustave Roussy Institute (Villejuif, France) as part of a translational research program on the tumor immune microenvironment in melanoma. Gene expression profiling was performed to characterize immune-related transcriptomic signatures and their association with circulating LDH isoenzyme patterns.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002219","title":"Intraclonal diversification in light chain genes in CLL","description":"This study identifies intraclonal diversification of immunoglobulin light chain genes in chronic lymphocytic leukemia.","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002220","title":"Comprehensive DNA and RNA profiling of relapsed interdigitating dendritic cell sarcoma in a patient achieving durable remission after autologous stem cell transplantation","description":"DNA- and RNA-based next-generation sequencing (NGS) panel profiling of a rare case of relapsed interdigitating dendritic cell sarcoma (IDCS) in an adult woman who achieved durable complete remission following chemotherapy and autologous stem cell transplantation. The dataset comprises raw sequencing data generated using the TruSight Oncology 500 panel for DNA analysis and the TruSight RNA Pan-Cancer Panel for RNA analysis.\r\n","abstract":null,"study_type":"Cancer Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002221","title":"Extreme drift in a hunter-gatherer population from Nepal","description":"Here we investigate the highly isolated Raute hunter-gatherers of western Nepal, revealing the most extreme documented case of population-wide autozygosity in humans. We show that this high autozygosity results mostly from persistent small effective population sizes and isolation due to strict cultural endogamy, rather than widespread consanguineous marriages. Our results suggest that population connectivity, rather than group size or autozygosity, may have been the fundamental determinant of long-term genomic and cultural resilience in humans.","abstract":null,"study_type":"Population Genomics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002222","title":"Prediction of benefit from adjuvant dose-dense chemotherapy for high-risk breast cancer: results from the randomized phase III PANTHER trial","description":"This study investigates molecular biomarkers associated with benefit from adjuvant dose-dense chemotherapy in patients with high-risk early breast cancer enrolled in the randomized phase III PANTHER trial. RNA sequencing data from tumour samples were used for transcriptomic analyses and biomarker evaluation. The deposited dataset comprises raw RNA-seq FASTQ files and is made available under controlled access.","abstract":null,"study_type":"RNASeq","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002223","title":"A persistent fetal-like progenitor underlies disease progression and relapse in Down syndrome myeloid leukemia","description":"Raw sequencing data (paired-end FASTQ) for the manuscript \"A persistent fetal-like progenitor underlies disease progression and relapse in Down syndrome myeloid leukemia\". The study holds four controlled-access datasets, one per data type: (1) bulk RNA-seq of paediatric myeloid leukaemias (TAM, ML-DS, AMKL, KMT2A-rearranged, NUP98-rearranged, t(8;21), inv(16), trisomy 8, NPM1-mutated and WT1-mutated AML) and of healthy haematopoietic cells (adult, cord blood and fetal liver CD34+ HSPCs, in-vitro erythroid and megakaryocytic cells); (2) ATAC-seq; (3) ERG CUT&RUN; and (4) CUT&Tag for H3K4me1, H3K27ac and H3K4me3, of primary ML-DS and other paediatric myeloid leukaemia samples and healthy CD34+-derived cells.","abstract":null,"study_type":"Epigenetics","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002224","title":"Molecular profiling of human bone marrow niche models in myelodysplastic neoplasms","description":"This study investigates hematopoietic maintenance and molecular features of engineered human bone marrow niches in myelodysplastic neoplasms (MDS). Single-cell RNA sequencing was performed on cells recovered after 21 days of perfusion culture from MDS-derived and healthy donor-derived bone marrow niche models to characterize hematopoietic and stromal cell populations and condition-associated transcriptional programs. Targeted panel sequencing was additionally used to assess patient-specific somatic mutations and changes in variant allele frequencies before and after culture. The submitted sequencing data support the transcriptomic and clonal analyses reported in the associated manuscript.","abstract":null,"study_type":"Transcriptome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002225","title":" ImmunogenomiC prOfiling of early-stage NSCLC (ICON)","description":"The ICON study is a prospective multiomics study on tumor, normal lung tissue and blood samples collected from resected lung cancers.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002226","title":"FiberTron: sequence-to-function modelling of single-molecule chromatin, DNA methylation and transcription in melanoma and clear cell sarcoma","description":"This study contains PacBio HiFi Fiber-Seq and Oxford Nanopore direct RNA-seq data generated to train and evaluate FiberTron, a lightweight multi-modal sequence-to-function deep learning model. From 524 kb of DNA sequence, FiberTron predicts base-resolution CpG methylation, chromatin accessibility and strand-specific transcription. Data were generated from a patient-derived melanoma cell line (MM001) and from a fresh-frozen metastatic clear cell sarcoma sample (CCS15). Data are aligned to T2T-CHM13v2.0 and used to model allele-specific effects.","abstract":null,"study_type":"Gene Regulation Study","pubmed_ids":[],"external_links":null,"is_released":false,"released_date":null,"is_deprecated":false},
{"accession_id":"EGAS50000002227","title":"Genetic landscape of kidney failure in Israel","description":"Kidney failure is a major cause of morbidity and mortality, and a substantial fraction of cases has an underlying monogenic cause that often remains undiagnosed. This study aimed to characterise the genetic landscape of kidney failure and to estimate the diagnostic yield of exome sequencing in a nationwide cohort of dialysis-treated patients in Israel. Proband exome sequencing was performed and variants were interpreted according to ACMG/AMP guidelines to identify molecular diagnoses in known kidney disease genes.","abstract":null,"study_type":"Exome Sequencing","pubmed_ids":[],"external_links":null,"is_released":true,"released_date":"2026-10-22T12:17:37.046201+02:00","is_deprecated":false}]